Skin Temperature Gradient Effects on the Variation of Metabolic Hormones in Adults
Skin Temperature Gradient Effects on the Variation of Metabolic Hormones in Adults
The Cyprus International Institute for Environmental and Public Health of the Cyprus
 University of Technology is planning a pilot study of health indicators in relation to
 spatially varying climatic conditions ranging from the city to the mountainous environment.
 The purpose of the project is to understand the effect of fluctuations in external climatic
 conditions on the human body temperature and metabolic biomarkers or stress hormones.

 Climate change phenomena such as protracted heat waves that create areas with even higher
 temperatures, especially in urban centers, may have a negative impact on human health. The
 effects may be acute for an individual with the appearance of discomfort and headaches, while
 chronic exposures to high air temperatures for the general population have been linked with
 premature mortality and cardiovascular diseases. Due to climate change that is hitting hard
 the Mediterranean, these temperature changes have been more and more common in Cyprus in
 recent years.

 One of the usual ways of dealing with high temperatures is the use of air conditioners. With
 sudden and frequent temperature changes during the day, the human body is subject to thermal
 shock for varying duration and number of times, having wear and tear consequences for the
 human physiology. The investigators hypothesized that the number, duration and frequency of
 human exposures to wide gradient (> 8 ° C) of air temperature changes may be related to
 potential health problems. An intervention potentially reducing the health risk associated
 with extended exposure to high temperatures in the summer for Cypriots may be the temporary
 (for a few days or hours) stay in the villages of mountainous area. Most of the mountain
 communities in Cyprus have consistently lower mean ambient air temperatures of about 10
 degrees Celsius than those in the cities, so the investigators anticipate not observing the
 metabolic hormone alterations induced while being in the city environment.
A randomised crossover trial study design was used to: investigate the circadian patterns of
 metabolic adipokines (leptin, adiponectin and ghrelin hormones), using targeted biomarker
 measurements and untargeted metabolomics in healthy adults residing in two different
 climatological environments: urban and higher in latitude mountainous settings, and ii)
 investigate the effect of skin temperature gradient on the variation of adipokines in the two
 settings (urban and rural).

 The study will take place in Cyprus. Participant recruitment will abide by the ethical
 principles and the guidelines of the National Bioethics Committee of Cyprus. Participants
 will be recruited after they read and complete the consent form and the whole study protocol
 is explained to them. Information about the study will be disseminated through flyers and
 through telephone communication via governmental and other non-profitable organizations that
 will contact community leaders of the area and help us collect and create a contact list of
 "Potential Participants". From there, potential participants will be informed about the study
 and screened for eligibility criteria via telephone.

 Upon consent, the "Potential Participants List" will have to be randomized to assign the
 participants in to two different groups. A total of 50-60 subjects will be followed for a
 period of one week firstly in an urban environment and later, for the same period, in a
 village of the mountainous rural environment, during the summer period in Cyprus.

 Once the researchers have names of potential participants, each name will be given a 2-digit
 code. This will be participant's study ID that will accompany participants answered
 questionnaires, diaries, urine vials and temperature measurement's files. The preparation of
 each tool with filled participants ID code and Date will be made at priory.

 There will be no blinding since the interventions are known to the participants and the
 researchers. There will be the necessary blinding during the conduct of the all laboratory
 and statistical analyses.

 The field workers and participants will arrange four visits. Visit 1 and 3 will take place
 one day before the sampling day which is the last day at each site(urban Vs rural), whereas
 visit 2 and 4 will take place a day after the sampling day when collection of the data will
 take place.

 Except the preparation for the first sampling day during the first visit, participants will
 be asked to sign the informed consent form and to fill in two survey questionnaires (baseline
 characteristics and chronotype questionnaire). During sampling days, participants will be
 handed with the diary of activities, urine vials for urine sample collection and the
 instructions form (for urine collection and the use of the personal temperature sensors).
 Electronic temperature sensors should be activated by the researchers on the spot and placed
 on the participant during the first and third visit. The temperature data collection will be
 ensured on the spot during the second and forth visit. Participants will be asked to collect
 urine voids by collecting all bladder content during urination in vials provided by the Water
 and Health Lab. The first urine void of each sampling day will be discarded. All urine voids
 for the rest of the sampling day, of each participant, will be collected, including the first
 urine void of the following day. Samples will be kept at a freezer by the participant until
 collected by a member of the research team, in cool boxes. Upon arrival at the Water and
 Health lab samples, aliquoting will take place and then aliquot samples will be stored in
 freezers of -80◦C, until analysis.

 Data collected will be digitized, anonymized and statistically evaluated. All data management
 steps will be employed to ensure that a final, clean, tidy and replicable dataset will be
 produced before proceeding to the statistical analysis. Descriptive statistics of the study
 population will be performed that will include parameters such as the mean and standard
 deviation for continuous variables and percentages for variables that indicate proportions.

 The effect of temperature gradient changes and hormonal level, as well as, differences in
 cortisol levels between and within subject variation will be examined. The statistical
 analyses will include a range of approaches from descriptive statistics to regression
 analysis and metabolomics analyses. Pre-post analyses, non-linear mixed effects models, will
 be used to identify correlations of the circadian rhythms of the participants between the two
 settings. Statistical evaluation and graphical presentation of results will be prepared for a
 final report and presentation. All statistical analyses will be conducted at the Water and
 Health laboratory.
Inclusion Criteria:

 -  Healthy adults between 20-60 years old

 -  Those that intend staying in mountainous area of Cyprus for the period of at least 1
 week between July and September 2018

 Exclusion Criteria:

 -  Pregnant women

 -  Obese individuals (>30 kg m-2)

 -  Those that have travelled to another country within one week of the study start date.

 -  People with history of hypertension or with diabetes or metabolic syndrome, or cancer.

 -  People receiving pharmaceutical treatment for impaired glucose levels and/or
 hypertension and/or antidepressants or thyroxin for thyroid disorders.