The Effect of Calcium Ions on the Electrophysiological Properties of Single ANO6 Channels.

Proteins belonging to the anoctamin (ANO) family form calcium-activated chloride channels (CaCCs). The most unusual member of this family, ANO6 (TMEM16F), simultaneously exhibits the functions of calcium-dependent scramblase and the ion channel. ANO6 affects the plasma membrane dynamics and phosphatidylserine transport; it is also involved in programmed cell death. The properties of ANO6 channels remain the subject of debate. In this study, we investigated the effect of variations in the intracellular and extracellular concentrations of calcium ions on the electrophysiological properties of endogenous ANO6 channels by recording single ANO6 channels. It has been demonstrated that (1) a high calcium concentration in an extracellular solution increases the activity of endogenous ANO6 channels, (2) the permeability of endogenous ANO6 channels for chloride ions is independent of the extracellular concentration of calcium ions, (3) that an increase in the intracellular calcium concentration leads to the activation of endogenous ANO6 channels with double amplitude, and (4) that the kinetics of the channel depend on the plasma membrane potential rather than the intracellular concentration of calcium ions. Our findings give grounds for proposing new mechanisms for the regulation of the ANO6 channel activity by calcium ions both at the inner and outer sides of the membrane.

Calcium chelation independent effects of BAPTA on endogenous ANO6 channels in HEK293T cells.

Selective calcium chelator 1,2-Bis(2-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid (BAPTA) is a common tool to investigate calcium signaling. However, BAPTA expresses various effects on intracellular calcium signaling, which are not related to its ability to bind Ca2+. In patch clamp experiments, we investigated calcium chelation independent effects of BAPTA on endogenous calcium-activated chloride channels ANO6 (TMEM16F) in HEK293T cells. We have found that application of BAPTA to intracellular solution led to two distinct effects on channels properties. On the one hand, application of BAPTA acutely reduced amplitude of endogenous ANO6 channels induced by 10 µM Ca2+ in single channel recordings. On the other hand, BAPTA application by itself induced ANO6 channel activity in the absence of the intracellular calcium elevation. Open channel probability was enhanced by increasing the intracellular BAPTA concentration from 0.1 to 1 and 10 mM. Another calcium chelator EGTA did not demonstrate chelation independent effects on the ANO6 activity in the same conditions. Due to off-target effects BAPTA should be used with caution when studying calcium-activated ANO6 channels.

[The Effects of the Hydrogen Sulfide Donor GYY4137 on the Proteasome Pool of Colorectal Cancer Cells].

Cancer cells are characterized by an increased level of metabolism and are highly dependent on the correct functioning of the processes that ensure homeostasis. Reactive sulfur species (RSS) are important molecular modulators of metabolic processes in both healthy and tumor cells. The effect of RSS and, in particular, H2S, on key cellular systems, including the ubiquitin-proteasome system (UPS), which provides the destruction of most intracellular proteins, has been shown. The main components of the UPS are proteasomes, multisubunit protein complexes, within which proteolysis occurs. At the same time, data on the effect of H2S directly on the pool of proteasomes in tumor cells are insufficient. Here, we studied the effect of incubation of SW620B8-mCherry colorectal adenocarcinoma cells expressing a fluorescently labeled proteasome subunit with 50, 100, and 200 µM of the hydrogen sulfide donor GYY4137. The effect of the substance on the proteasome pool was assessed 6, 24, 48, and 72 h after administration. It was shown that the chymotrypsin-like and caspase-like proteasome activity decreases in cells incubated with 200 µM of the GYY4137 for 24 h. This coincided with an increase in the expression of proteasome subunit genes. In lysates of cells incubated with 200 µM GYY4137 for 48 h an increase in the content of the constitutive ß5 subunit was observed and the activity of proteasomes leveled off. Following prolonged incubation with GYY4137 (72h), an increase in the expression levels of some proteasome genes was also observed, although this did not have a significant effect on the activity and subunit composition of proteasomes. Thus, the obtained data indicate the modulation of proteasome activity by the hydrogen sulfide donor and the effect of GYY4137 on transcription and translation of proteasome genes.

Universal thermal climate index in the Arctic in an era of climate change: Alaska and Chukotka as a case study.

The modern unambiguous climate change reveals in a rapid increase of air temperature, which is more distinctly expressed in the Arctic than in any other part of the world, affecting people health and well-being. The main objective of the current research is to explore the inter- and intra-annual changes in thermal stress for people in the Arctic, specifically for two parts of Beringia: Alaska, USA, and Chukotka, Russia, using climatology of the universal thermal climate index (UTCI). Data for 39 locations are taken from the ERA5-HEAT reanalysis for the period 1979-2020. Climatologically, the study area is divided into four subregions in Alaska: North, Interior, West and South, and two in Chukotka: Interior and Coast. The extreme coldest UTCI categories (1 and 2) are most common in coastal locations of northern Alaska and Chukotka, where strong winds exacerbate the low temperatures during winter. The results show that the frequency of category 1 (UTCI<-40°C) varies spatially from a quarter of all hours annually in Alaska North to almost zero in Alaska South. On the other hand, the warmest categories are rarely reached almost everywhere in Alaska and Chukotka, and even categories 7 and 8 (UTCI between +26 and +38°C) are found occasionally only at interior locations. Category 6 with no thermal stress (UTCI between +9 and+26°C) has frequencies up to 3% and 25% in Alaska North and Interior, respectively. The extremely cold thermal stress frequencies have substantially decreased over the 1979-2020 period, especially in Alaska North and Chukotka Coast. At the same time, the number of hours with UTCI in the comfortable category of thermal perception has increased depending on subregion, from 25 to 203 h/year. Overall, a decrease in the UTCI categories of extremely cold stress is coupled with an increase in the comfortable range in both Alaska and Chukotka. The salient conclusion is that, from the point of view of comfort and safety, global warming has a positive impact on the climatology of thermal stress in the Arctic, providing advantages for the development of tourism and recreation.

[Second-generation long-acting injectable antipsychotics in clinical practice]. / In"ektsionnye antipsikhotiki-prolongi vtoroi generatsii v klinicheskoi praktike.

On the example of 5 clinical cases of paranoid schizophrenia at different stages of the development of the disease, the therapeutic tactics of using drugs from the group of second-generation injectable prolong antipsychotics to solve problems that arise during anti-relapse therapy are shown. The research data substantiating these approaches are presented. Various combination therapy options are discussed, including at the stage of drug replacement and the appointment of a second-generation long-acting injectable antipsychotic.

[Long-term postoperative outcomes in patients with drug-resistant epilepsy]. / Otdalennye rezul'taty khirurgicheskogo lecheniya patsientov s farmakorezistentnymi formami epilepsii.

Epilepsy surgery is effective in 30-82% of patients with drug-resistant epilepsy. However, risk factors of unfavorable outcomes after epilepsy surgery require further study. OBJECTIVE: To evaluate risk factors of favorable and unfavorable long-term postoperative outcomes in patients with drug-resistant epilepsy. MATERIAL AND METHODS: Postoperative outcomes in a large cohort of patients with epilepsy are reported for the first time in the Russian Federation. There were 271 patients with drug-resistant scheduled for surgery. Preoperative examination and surgical treatment were carried out between January 1, 2014 and December 12, 2019 at the Evdokimov Moscow State University of Medicine and Dentistry and Sklifosovsky Research Institute for Emergency Care. We used Engel grading system to assess postoperative outcomes after 12, 24, 48 and 60 months. We distinguished favorable (Engel I-II) and unfavorable (Engel III-IV) outcomes and analyzed the factors influencing postoperative results in these patients. RESULTS: There were 319 surgical procedures in 271 patients (217 primary resections, implantation of vagus nerve stimulator in 31 patients, 9 redo resections and 8 radiosurgical procedures). Focal cortical dysplasia (FCD) was found in 162 (60%) patients, «dual pathology¼ - in 118 (44%) cases. In 12 months after surgery, favorable outcomes (Engel l-II) were observed in 69% of patients (n=148), after 24 months - in 71% (n=127) of patients. Postoperative complications occurred in 6 (1.9%) patients. There was no mortality. The earlier onset of epilepsy (p=0.01), multifocal (p=0.002) and bilateral lesions (p=0.0038) were the most significant risk factors of unfavorable postoperative outcomes. CONCLUSION: Surgical resection is effective approach for drug-resistant epilepsy.

[Resection of S1 root schwannoma with extravertebral retroperitoneal spread via posterior median and laparoscopic approach]. / Odnomomentnoe udalenie nevrinomy pravogo spinnomozgovogo koreshka S1 s ekstravertebral'nym retroperitoneal'nym rasprostraneniem zadnim sredinnym i laparoskopicheskim dostupom (klinicheskoe nablyudenie).

The authors report simultaneous surgical treatment of the right S1 root schwannoma with extravertebral retroperitoneal spread. Well-equipped operating theatre, professional experience and multidisciplinary approach involving neurosurgeons and abdominal surgeons ensure total minimally invasive simultaneous resection of schwannoma via posterior median and laparoscopic approach.

[Elderly mortality at the Russian Far East: seasonality and mitigation].

In many countries of the world, demographic changes have occurred, characterized by an increase in the share of socially inactive elderly people. The goal is a medical and demographic analysis of the elderly in the Far East. For Khabarovsk and Birobidzhan, seasonal patterns of mortality and self-preserving behavior of older people were investigated. In order to determine the actions and personal attitudes of self-preserving behavior for the prevention of cardiovascular diseases, elderly people who visited the Vertical fitness center in Birobidzhan were interviewed. It was found that the overall mortality rate among older people is higher among men than among women. The main causes of death are cardiovascular diseases, which have a pronounced seasonality with a maximum in winter. It is shown that 23% of men and 48% of women do not demonstrate high social and physical activity and do not have any skills to maintain their health.

[Analysis of local hemodynamics in complex aneurysms: an effect of the vessel arising from the dome or the neck]. / Issledovanie lokal'noi gemodinamiki v slozhnykh anevrizmakh: vliyanie sosuda, otkhodyashchego ot kupola ili sheiki.

BACKGROUND: Assessment of rupture risk for intracranial aneurysms (IA) is a particular challenge in cases of so-called complex aneurysms due to their variable morphometric characteristics. Arterial branch arising from the dome or the neck of IA is one of the least explored features of complex aneurysms. The methods of computational fluid dynamics may be valuable to determine the influence of arterial branches of IA on local hemodynamics. OBJECTIVE: To analyze local hemodynamics in IA with arterial branch arising from the cupola or the neck depending on the structure of the aneurysm and blood flow rate in the parent vessel. MATERIAL AND METHODS: CT angiography data of 4 patients with IA were estimated in this study. Modifications of the baseline 3D models of the aneurysms resulted 12 patient-specific models included into analysis. Hemodynamic calculations were made by using of ANSYS Workbench 19 software package. RESULTS: Wall shear stress (WSS) was characterized by the most significant variability, especially in case of sidewall aneurysms. Small cross-sectional area of additional branch in relation to the neck of IA was not followed by considerable changes of blood flow patterns inside IA after «virtual¼ removal of the vessel. Otherwise, the intensity of flows was drastically reduced. Simulation of high inlet flows demonstrated substantial variation of WSS in the area of jet. CONCLUSION: Additional arterial branch arising from the dome or the neck of IA significantly influences local hemodynamics. This influence depends on the localization of IA in relation to the parent vessel and the diameter of additional arterial branch.

The comparison of the process of manual and robotic positioning of the electrode performing radiofrequency ablation under the control of a surgical navigation system.

This study is aimed at the comparison of the process of manual and robotic positioning of the electrode performing radiofrequency ablation under the control of a surgical navigation system. The main hypothesis of this experiment was that the use of a collaborative manipulator (KUKA iiwa) will allow to position the active part of the electrode relative to the center of the tumor more accurately and from the first attempt. We also monitor the stability of the electrode's velocity during insertion and consider some advantages in ergonomics using the robotic manipulator. We use three more criteria to compare the surgeon's and robotic performance, unlike other studies, where only the target point's accuracy criterion is observed. The main idea is to examine the movement parameters of the electrode that can lead to potential patient trauma. Sphere-shaped tumor phantoms measuring 8 mm in diameter were filled with contrast and inserted in bovine livers. 10 livers were used for the robotic experiment and an equal quantity for manual surgery. The livers were encased in silicone phantoms designed to imitate the liver position in a real patient's abdominal cavity. Analysis of CT data gave the opportunity to find the entry and the target point for each tumor phantom. This data was loaded into a surgical navigation system that was used to track and record the position of the RF-electrode during the operation for further analysis. The standard deviation of points from the programmed linear trajectory totaled in the average 0.3 mm for the robotic experiment and 2.33 mm for the manual operation with a maximum deviation of 0.55 mm and 7.99 mm respectively. Standard deviation from the target point was 2.69 mm for the collaborative method and 2.49 mm for the manual method. The average velocity was 2.97 mm/s for the manipulator and 3.12 mm/s for the manual method, but the standard deviation of the velocity relative to the value of the average velocity was 0.66 mm/s and 3.05 mm/s respectively. Thus, in two criteria out of three, the manipulator is superior to the surgeon, and equality is established in one. Surgeons also noticed advantages in ergonomics performing the procedure using the manipulator. This experiment was produced as part of the work on the developing of a robotic multifunctional surgical complex. We can confirm the potential advantages of using collaborative robotic manipulators for minimally invasive surgery in case of practice for cancer treatment.

Protective Properties of Lanthanum Nitrate against Pathogens with Various Morphological and Functional Properties.

Dose-dependent protective effects of lanthanum nitrate solution and gel were shown on the model of experimental infection caused by a virulent strain of Shigella flexneri 2a or opportunistic bacteria Klebsiella pneumoniae in outbred and DBA mice.

An Assessment of Radiation-Associated Risks of Mortality from Circulatory Disease in the Cohorts of Mayak and Sellafield Nuclear Workers.

Mortality from circulatory disease (CD), ischemic heart disease (IHD) and cerebrovascular disease (CeVD) was investigated in relationship to cumulative doses of external gamma radiation and internal alpha radiation to the liver from deposited plutonium over long follow-up periods in two large cohorts of nuclear workers: the Russian Mayak Worker Cohort (MWC) and the UK Sellafield Worker Cohort (SWC). The MWC comprised 22,374 workers (74.6% males) with 5,123 CD deaths registered during 842,538 person-years of follow-up, while the SWC comprised 23,443 workers (87.8% males) with 2,322 CD deaths registered during 602,311 person-years of follow-up. Dose estimates for external gamma radiation and internal alpha radiation to the liver were calculated via a common methodology, in accordance with an agreed protocol. The mean cumulative external Hp(10) dose was 0.52 Sv for the MWC and 0.07 Sv for the SWC, while the mean cumulative internal dose was 0.19 Gy for the MWC and 0.01 Gy for the SWC. Categorical relative risks (RR) and excess relative risks (ERR) per unit dose were estimated for each cohort and for the pooled cohort when appropriate. The dose responses for CD, IHD and CeVD in relationship to internal alpha-particle dose did not differ significantly from the null for either the MWC, the SWC or the pooled plutonium worker cohort. The ERR/Sv estimates in relationship to external exposure were significantly raised for both cohorts (marginally so for the MWC) for CD and IHD (but not for CeVD), but differed significantly between the two cohorts, the estimate for the SWC being approximately ten times greater than that for the MWC. Examination of the ERR/Sv estimates for two periods of first employment at the two facilities revealed that the significant heterogeneity was confined to the earlier sub-cohorts, and that the estimates for the later sub-cohorts were compatible. The two sub-cohorts for the later first-employment periods were pooled, producing risk estimates that were raised, but not significantly so: ERR/Sv for CD, IHD and CeVD of 0.22 (95% CI: -0.01, 0.49), 0.22 (95% CI: -0.06, 0.57) and 0.24 (95% CI: -0.17, 0.80), respectively. The reasons for the complex pattern of results found in this study are unclear. Among potential explanations are the influence of differences in background CD mortality rates, an effect of other occupational factors, substantial uncertainties in doses, particularly during earlier periods of operations, as well as confounding and/or modifying factors that were not taken into account in the current analysis.

A comparison and appraisal of a comprehensive range of human thermal climate indices.

Numerous human thermal climate indices have been proposed. It is a manifestation of the perceived importance of the thermal environment within the scientific community and a desire to quantify it. Schemes used differ in approach according to the number of variables taken into account, the rationale employed, and the particular design for application. They also vary considerably in type and quality, method used to express output, as well as in several other aspects. In light of this, a three-stage project was undertaken to deliver a comprehensive documentation, classification, and overall evaluation of the full range of existing human thermal climate indices. The first stage of the project produced a comprehensive register of as many thermal indices as could be found, 165 in all. The second stage devised a sorting scheme of these human thermal climate indices that grouped them according to eight primary classification categories. This, the third stage of the project, evaluates the indices. Six evaluation criteria, namely validity, usability, transparency, sophistication, completeness, and scope, are used collectively as evaluation criteria to rate each index scheme. The evaluation criteria are used to assign a score that varies between 1 and 5, 5 being the highest. The indices with the highest in each of the eight primary classification categories are discussed. The work is the final stage of a study of the all human thermal climatic indices that could be found in literature. Others have considered the topic, but this study is the first detailed, genuinely comprehensive, and systematic comparison. The results make it simpler to locate and compare indices. It is now easier for users to reflect on the merits of all available thermal indices and decide which is most suitable for a particular application or investigation.

[Outcomes of surgical treatment of patients with pharmacoresistant epilepsy]. / Iskhody khirurgicheskogo lecheniya patsientov s farmakorezistentnymi formami epilepsii.

AIM: To evaluate the results of surgical treatment of patients with pharmacoresistant epilepsy. MATERIAL AND METHODS: Examination and surgical treatment of 61 patients with pharmacoresistant forms of symptomatic epilepsy were performed from 01.01.14 to 01.05.16. RESULTS AND CONCLUSION: The results confirmed the safety and efficacy of the surgical treatment of pharmacoresistant epilepsy. After 12 months, seizures were controlled in 69% of operated patients. The necessity of complex examination of all patients with pharmacoresistant epilepsy to make a decision about possible surgery is shown.

[Operations of revascularization in surgery of cerebrovascular aneurysms].

Surgical revascularization of the brain is one of the most important trends in the development of neurosurgery. Restoration of adequate blood flow through pre- and intracerebral arteries promotes prevention and treatment of ischaemic lesions of the brain in various pathology. The present work was aimed at analysing the experience gained in performing revascularizing operations in patients with cerebral aneurysms at the department of neurosurgery. The authors analysed therapeutic outcomes in a total of 45 patients presenting with giant and complex aneurysms of cerebral arteries and treated from 2009 to 2014. Of the 45 patients with giant and complex aneurysms of cerebral arteries, 31 (68.8%) patients underwent open microsurgical interventions (including 10 patients with the use of different variants of revascularizing operation) and 14 (31.2%) patients were subjected to endovascular exclusion of the aneurysm from the blood flow. It was shown that performing revascularizing operations in patients with complex and giant aneurysms of cerebral arteries makes it possible to compensate circulation in the interested arterial basin and to obtain good functional results.

[TREATMENT OF PATIENTS WITH CHRONIC RECURRENT HERPES VIRUS INFECTION OF GENITAL LOCALIZATION: A CLINICAL STUDY OF FORTEPREN PREPARATION].

AIM: Selection of optimal dosage regimen, length of treatment course (frequency of administration), safety, tolerance and clinical effectiveness evaluation of the medical preparation fortepren in patients with chronical recurrent herpes virus infection of genital localization. MATERIALS AND METHODS: The medical product of antiviral and immune modulating effect--fortepren (sodium polyprenyl phosphate) as a 4 mg/ml solution for injections combined with the base course of acyclic nucleoside acyclovir, 400 mg tablets, held studies. 40 male and female patients participated in the study. After a 10-day acyclovir course (400 mg x 3 times a day) for removing the acute phase, 4 groups of 10 individuals were formed: 1--5 ml (20 mg) of fortepren i/m once at day 13 ± 2 after the start of the study after the completion of the treatment of the acute phase of the disease; 2--5 ml (20 mg) fortepren i/m 3 times at an interval of 21 days; 3--2 ml (8 mg) fortepren i/m 3 times at an interval of 21 days; 4 (control)--5 ml of placebo i/m at remission stage 3 times at an interval of 21 days. Increase of the duration of inter-recurrence period, decrease of the severity of the recurrences, state of skin and mucous damage elements, improvements of immunologic parameters were considered during effectiveness evaluation. RESULTS: Significant differences in the frequency of recurrences of genital herpes were shown for 3 months of observation in experimental and control groups. A significant reduction of genital herpes recurrence frequency from 3.52 ± 0.09 (before treatment) to 2.89 ± 0.08 (after treatment) was noted in patients of group 3 (p < 0.001). The frequency of recurrences in the control group was 3.84 ± 0.10, that was higher than the parameters in all the experimental groups. A significant reduction of the rash area was noted in group 3, moreover, a redution of frequency of detection of clinical manifestations of genital herpes in the form of vesicle elements after treatment in groups 2 (p = 0.02) and 3 (p = 0.005) was found. Evaluation of local symptoms has established that burning have caused minimal discomfort for patients of groups 3 and 4 and itch and soreness--of groups 1 and 3. The least pronounced exacerbations were noted in patients of group 3. Intramuscular administration of fortepren preparation was established to result in the increase of titers of leukocyte virus-induced interferon for the whole duration of treatment. CONCLUSION: An intramuscular dose of 2 ml (8 mg) at recurrence stage 3 times at an interval of 21 days after the completion of the 10-day base course of treatment of the acute phase of chronical recurrent herpes virus infection of genital localization using acyclovir was accepted as an optimal dosage regimen. Analysis of the obtained results has shown an acceptable safety profile and a good level of tolerance for fortepren preparation.

Antitumor efficacy of extracellular complexes with gadolinium in Binary Radiotherapy.

In this report the efficacy of extracellular pharmaceutical Gd-DTPA in Binary Radiotherapy was studied. The study was carried out in mice bearing transplantable adenocarcinoma Ca755 using X-ray based contrast enhanced radiotherapy as a practical implementation of Binary Radiotherapy. It was shown that intravenous administration of 0.3 ml of 0.5 M water solution of Gd-DTPA followed by X-irradiation at a dose of 10 Gy provides T/C%=10±3% and leads to complete tumor regression in 25% of mice.

Risk of mortality from circulatory diseases in Mayak workers cohort following occupational radiation exposure.

Mortality from circulatory diseases (CD) (ICD-9 codes 390-459) was studied in an extended Mayak worker cohort, which included 22,377 workers first employed at the Mayak Production Association in 1948-1982 and followed up to the end of 2008. The enlarged cohort and extended follow-up as compared to the previous analyses provided an increased number of deaths from CD and improved statistical power of this mortality study. The analyses were based on dose estimates provided by a new Mayak Worker Dosimetry System 2008 (MWDS-2008). For the first time in the study of non-cancer effects in this cohort quantitative smoking data (smoking index) were taken into account. A significant increasing trend for CD mortality with increasing dose from external gamma-rays was found after having adjusted for non-radiation factors; the excess relative risk per unit dose (ERR/Gy) was 0.05 (95% confidence interval (CI): >0, 0.11). Inclusion of an additional adjustment for dose from internal alpha-radiation to the liver resulted in a two-fold increase of ERR/Gy = 0.10 (95% CI: 0.02, 0.21). A significant increasing trend in CD mortality with increasing dose from internal alpha-radiation to the liver was observed (ERR/Gy = 0.27, 95% CI: 0.12, 0.48). However the ERR/Gy decreased and lost its significance after adjusting for dose from external gamma-rays. Results of the current study are in good agreement with risk estimates obtained for the Japanese LSS cohort as well as other studies of cohorts of nuclear workers.

A comprehensive catalogue and classification of human thermal climate indices.

The very large number of human thermal climate indices that have been proposed over the past 100 years or so is a manifestation of the perceived importance within the scientific community of the thermal environment and the desire to quantify it. Schemes used differ in approach according to the number of variables taken into account, the rationale employed, the relative sophistication of the underlying body-atmosphere heat exchange theory and the particular design for application. They also vary considerably in type and quality, as well as in several other aspects. Reviews appear in the literature, but they cover a limited number of indices. A project that produces a comprehensive documentation, classification and overall evaluation of the full range of existing human thermal climate indices has never been attempted. This paper deals with documentation and classification. A subsequent report will focus on evaluation. Here a comprehensive register of 162 thermal indices is assembled and a sorting scheme devised that groups them according to eight primary classification classes. It is the first stage in a project to organise and evaluate the full range of all human thermal climate indices. The work, when completed, will make it easier for users to reflect on the merits of all available thermal indices. It will be simpler to locate and compare indices and decide which is most appropriate for a particular application or investigation.

The impact of acclimatization on thermophysiological strain for contrasting regional climates.

During acclimatization to heat and cold, the body experiences additional thermally induced physiological strain. The first signs show up in the respiratory organs because respiration is a continuous heat exchange process in which the body is in closest contact with the ambient air. There are no behavioral or other adjustments to prevent the ambient air from entering into the body's core area through the respiratory tract. The Acclimatization Thermal Strain Index (ATSI) describes the acclimatization thermal loading (ATL) on respiratory organs until full adaptation is achieved. The aim here is to further assess the ATSI scheme using a range of actual but contrasting bioclimatic conditions. To simulate ATL, scenarios of the consequences of acclimatization due to movement to or from five contrasting climates are used. The results show that adjusting to cold comes with greater physiological strain than adjusting to heat, the biggest impact occurring for a change of location from hot-humid to cold-dry climatic conditions. The approach can be used to assess risks due to increases in short-term thermal variability in weather conditions such as encountered during heat waves and cold snaps. The information could also be useful for assessing the need for public health services and measures that might be used to help mitigate impacts.