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Subject: Research Services to Explore the Role of Estrogen Deficiency on Heat Acclimation and Organ Damage in Exertional Heat Stroke in Mice, U.S. Army Research Institute of Environmental Medicine (USARIEM)

THIS IS NOT A REQUEST FOR PROPOSALS (RFP) OR A REQUEST FOR QUOTATIONS (RFQ);

IT IS STRICTLY A REQUEST FOR INFORMATION (RFI). NEITHER UNSOLICITED PROPOSALS

NOR ANY OTHER KINDS OF OFFERS WILL BE CONSIDERED IN RESPONSE TO THIS RFI. NO

CONTRACT WILL BE AWARDED PURSUANT TO THIS ANNOUNCEMENT.

1.0 DISCLAIMER: This RFI is issued solely for information and planning purposes and does not constitute a solicitation. Neither unsolicited proposals nor any other kind of offers will be considered in response to this RFI. Responses to this notice are not offers and will not be accepted by the Government to form a binding contract. Responders are solely responsible for all expenses associated with responding to this RFI. All information received in response to this RFI that is marked Proprietary will be handled accordingly. Responses to the RFI will not be returned. At this time, questions concerning the composition and requirements for a future RFP will not be entertained.

2.0 SUBJECT: The purpose of this requirement is to determine the role of estrogen deficiency on heat acclimation and on the subsequent response to exertional heat stroke in female mice. The hypothesis is that estrogen deficient mice will display a blunted adaptation to heat acclimation and will be more susceptible to EHS-induced organ damage.

Exertional heat stroke (EHS) is a major military medical problem. Besides resulting in a loss of duty time, EHS leads to long-term negative health outcomes. Most studies of EHS pathophysiology are performed in males and much less is known about the response in females. Understanding how females respond to EHS and the role of estrogen on thermoregulatory response will allow for the development of interventions specifically tailored to prevent and/or treat EHS in women.

Sex-dependent differences exist in response to EHS. A recent study suggested that female mice are ~40% more resistant than male mice during exertion in the heat. This difference cannot be fully explained by increased body surface/mass ratio in females or on differences in aerobic performance.

Hormonal differences (e.g. estrogen) may play a pivotal role and further explain the unique response to EHS observed in females.

Heat acclimation (HA) has been suggested as a preventative measure against EHS. HA consists of a series of adaptations that occur in response to repeated heat exposures. These adaptations are beneficial in that they help improve performance and allow the organism to better handle heat stress.

Although sex differences have been reported in HA, the role of estrogen in the HA adaptations and potential protection against EHS-induced organ damage remains unknown

3.0 BACKGROUND: The Thermal and Mountain Medicine Division is one of four research divisions within the U.S. Army Research Institute of Environmental Medicine (USARIEM).

USARIEM's mission is to optimize Warfighter health and performance through medical research.

USARIEM is internationally recognized as the premiere DoD laboratory for Warfighter health and performance research and focuses on environmental medicine, physiology, physical and cognitive performance, and nutrition research. USARIEM publishes guidance for DOD operations for both hot and cold weather, high-altitude environments, and nutrition for optimal health and performance.

The mission of the Thermal and Mountain Medicine Division is to conduct field and laboratory research on medical and physiological problems encountered by military personnel during acute and chronic exposure to environmental extremes. Research goals include: to determine the limits of physical exercise including nutritional and metabolic factors; to investigate new methods to improve those decrements; and to assess relative changes in normal physiological and psychological functions as evidenced in the related effects on overall performance. The division is responsible for investigating and developing new approaches to improve military effectiveness based on scientific knowledge in the areas of physiology, biochemistry, pharmacology, and nutrition.

4.0 RESPONSE INSTRUCTIONS: Respondents should address the following in their capabilities statement:

Task 1: Performance Requirements:

1.1. The contractor shall provide all necessary personnel required to perform services supporting the Thermal and Mountain Medicine Division. The contractor shall provide Research Support Services to determine the role of estrogen deficiency on heat acclimation and organ damage in EHS in mice. The following section specifies the Performance Objectives and Performance Elements for the contract.

1.1.1. Performance Objectives and Performance Elements

The goal of this work is to determine the role of estrogen deficiency on heat acclimation and organ damage in EHS in female mice. The contractor shall:

a) Conduct survival surgeries to implant telemetry devices and induce bilateral ovariectomy/sham.

b) Conduct daily acclimation/sham sessions in all animals for a consecutive period of 7 days.

c) Conduct experiments using a mouse EHS model currently used at USARIEM, where forced wheel running is combined with heat stress.

d) Determine cytokine and heat shock protein levels in plasma and/or tissues and the extent of histological injury in heat stroked mice.

e) Analyze the thermoregulatory profiles during EHS recovery to establish the role of estrogen on acclimation.

f) Write a final technical report on research findings

5.0 CONTACT INFORMATION: Any and all questions related to this RFI shall be directed to Mr.

Nathaniel Reus at nathaniel.a.reus.civ@mail.mil. All information regarding Capabilities Statements or any other proprietary information relative to this RFI shall be submitted via email to nathaniel.a.reus.civ@mail.mil no later than 2:00 p.m. E.S.T. on Monday, 11 January 2021.

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