Full Text PA-97-025
NIH GUIDE, Volume 26, Number 2, January 17, 1997
PA NUMBER:  PA-97-025
P.T. 34

  Musculoskeletal System 
  Muscle Disorders 

National Institute of Arthritis and Musculoskeletal and Skin Diseases
National Institute of Child Health and Human Development
National Institute of Nursing Research
The National Institute of Arthritis and Musculoskeletal and Skin
Diseases (NIAMS) and the National Institute of Nursing Research
(NINR) invite investigator-initiated research grant applications to
study a broad range of basic and clinical topics related to
musculoskeletal fitness, exercise physiology and sports medicine.
The National Center for Medical Rehabilitation Research of the
National Institute of Child Health and Human Development
(NCMRR/NICHD) encourages applications for both basic and clinical
studies of  musculoskeletal fitness and exercise physiology of
persons with physical disabilities.
The Public Health Service (PHS) is committed to achieving the health
promotion and disease prevention objectives of "Healthy People 2000,"
a PHS-led national activity for setting priority areas.  This Program
Announcement (PA), Research on Musculoskeletal Fitness and Sports
Medicine, is related to the priority area of physical activity and
fitness.  Potential applicants may obtain a copy of "Healthy People
2000" (Full Report:  Stock No. 017-001-00474-0) or "Healthy People
2000" (Summary Report:  Stock No. 017-001-00473-1) through the
Superintendent of Documents, Government Printing Office, Washington,
D.C. 20402-9325 (telephone 202-783-3238).  The PA is related to
issues in the 1996 Surgeon General's Report on "Physical Activity and
Health" (Stock No. 017-023-00196-5).
Applications may be submitted by domestic and foreign, for-profit
organizations, public and private, such as universities, colleges,
hospitals, laboratories, units of State or local governments, and
eligible agencies of the Federal government.  Foreign institutions
are eligible to apply for regular research project grants (R01).
Under this program announcement, the NIAMS and NICHD will support
investigator-initiated research project grants (R01), First
Independent Research Support and Transition (FIRST) (R29) awards,
small grants (R03), program projects (P01), career development grants
(K01, K02, K08), and Investigator-Initiated Interactive Research
Project Grants  (IRPG.)  The IRPG is described in PA-96-001,
published in the NIH GUIDE, Vol. 24, No. 35, October 6, 1995.  The
Principal Investigator and participating investigators will plan,
direct, and perform the research.  Applicants for program project
grants are requested to contact the NIAMS representative listed below
as early as possible in the planning stages.  The NINR will support
individual research project grants (R01 and R29.)
Physical activity builds strong muscles and bones and improves
flexibility and balance at all stages of life.  Musculoskeletal
fitness and physical activity protects individuals against over-
exertion or strains, preventing consequences including low back pain,
muscle tears, bone fractures, tendon ruptures, and other disorders.
Musculoskeletal fitness delays the onset of frailty as people age and
protects against disorders like osteoporosis.  Additionally, fitness
lowers risk for obesity, cardiovascular disease, and other chronic
illnesses.  There is not a strong scientific research basis for
understanding how the body integrates molecular mechanisms to
coordinate fitness in muscle, bone, tendon, and ligament.
Recent surveys included in the Surgeon General's Report on Physical
Fitness show that approximately one-fourth of  U.S. adults are
physically inactive.  It is important to promote exercise for
inactive people that improves fitness yet does not seem onerous.
While we know much of the vigorous regimens used by body-builders and
long distance runners, we have little experimental evidence of how
shorter, more focussed patterns of exercise can effectively build
muscle and bone strength.  We have even less information about the
physiological bases for appropriate musculoskeletal rehabilitation
interventions and the exercise needs of persons with physical
There is a health problem also for those who engage in extremely
strenuous exercise or sports regimens.  More than 30 million young
Americans participate in organized competitive sports, and one of
every two adult Americans exercises regularly.  This has lead to an
increase in activity-related injuries, which is substantial,
extending beyond sports into its impact on the workforce. It has been
estimated that 17 million persons in this country sustain significant
injury from sports or recreational participation yearly.  One-third
of the 15 million joggers will sustain an injury that involves the
musculoskeletal system.  During 1995 football injuries resulted in
390,000 emergency room visits, while skiing resulted in 330,000
visits.  Evidently understanding the causes, prevention, and
treatment of athletic and recreational injury is a major health
Many currently recommended sports and exercise practices are not
based on strong scientific evidence.  The empirical designs of many
protective devices are not founded in fundamental biomechanical
studies.  Additionally, there is a strong scientific understanding of
the normal physiology of muscle, but not a large base of research
into muscle metabolism, hypertrophy and injury during exercise,
strength training, and disuse.  Feedback mechanisms by which the
muscle senses and communicates its mechanical requirements are
unknown.  Similarly, bone strength increases following muscle
strength, but the molecular couplers of the two actions have not been
Research efforts have yielded many improvements in training athletes,
preventing injuries and treating patients.  Technological advances
have improved the practice of sports medicine. Further improvements
in the use of new technologies and information systems are likely to
improve methods of preventing, diagnosing, and treating sports
injuries.  Surveillance and treatment can be improved with the
development of standard and normative measures of musculoskeletal
Improved knowledge can be gained through increased basic science
research related to sports medicine and in applying the information
gained to practical problems in this field.  NIAMS promotes increased
basic science research related to exercise and sports medicine to
gain improved knowledge about normative measures of musculoskeletal
fitness.  An aim is to develop appropriate exercise patterns to build
muscle and bone strength for men and women who are relatively
inactive as well as world class athletes.  Exercise patterns should
be appropriate throughout the life spectrum, and not limited by
performance level or the presence of physical or psychological
Objectives and Scope
This solicitation is intended to stimulate research that provides an
expanded foundation of basic science knowledge related to
musculoskeletal fitness and sports medicine.  Additionally, it is
intended to encourage use of the best available scientific
information in important clinical and applied aspects related to
exercise, training, prevention, treatment and rehabilitation.
This program announcement includes a wide range of basic and applied
research on various aspects of musculoskeletal fitness.  Applicants
are encouraged to submit high scientific quality research projects in
any area related to the broad objectives of this program
announcement.  No order or priority of areas of interest has been
General Considerations - A large research effort is required to
establish a firm scientific foundation for a basic and applied
program in musculoskeletal fitness and sports medicine. Several
aspects of musculoskeletal fitness and injury require increased
knowledge:  athletic performance during competition; training and
prevention; treatment, and rehabilitation. Research in these areas
may involve various types of individuals, such as young children,
adolescents, mature adults, aged, professional athletes, men or
women.  Because the appropriate fitness information may be different
for each type of individual as they experience different possible
phases of musculoskeletal fitness or injury, research should be
carefully directed to the results applied to a particular
combination.  This includes differences between endurance and
resistance exercise regimens.
Examples of investigations of interest to the NIAMS include but are
not limited to research on:
1.  Muscle Physiology and Metabolism - Studies on changes in
metabolic, structural and contractile proteins following patterns of
disuse, and endurance and resistance strength training. Explore the
interrelationships and molecular steps between mechanical stimuli and
biochemical changes.  Determine how molecular responses differ
depending on demands of endurance and resistance training.  Relate
altered use of chemical fuel to training status of muscle,
performance responses, and health prevention.  Investigate changes in
fiber recruitment patterns and motor unit control.  Develop a
mechanistic understanding of the growth and maturation of muscle as
related to use and specialization.
2.  Muscle membranes  - Studies on changes on both external and
internal muscle membranes (e.g. sarcoplasmic reticulum) in response
to patterns of use.  This includes studies on receptors for
circulating factors (hormones), complexes involved in
excitation-contraction coupling, and surfaces involved in the
transfer of force, such as the extracellular matrix and the
myotendinous junction.
3.  Exercise Pathophysiology - Investigations of the damage and
healing of tissue from factors such as mechanical or thermal
overloading or systemic biochemical changes.  Study molecular bases
of fatigue in contractile, metabolic, and excitation-contraction
systems.  Explore the role of heat shock proteins in protecting
tissue during bouts of mild or extreme hyperthermia.
4.  Injury Mechanisms - Determine the mechanical forces and
biochemical environments that weaken and injure muscle, bone, and
connective tissues.  Establish the forces and force distributions
within joint structures and tissues, both during normal function and
during trauma. Explore influence of age and gender on structural
aspects that might influence location and severity of specific types
of injury.  Establish the conditions present during competitive
sports and recreational activities that may lead to damaged tissue.
Compare overuse versus traumatic injuries.  Investigate the role of
neuromuscular control and fatigue in injuries.
5.  Role of Exercise in the Prevention and Treatment of Bone and
Joint Diseases -  Explore the interrelationships and molecular steps
between mechanical stimuli and biochemical changes. Determine how
molecular responses differ depending on demands of endurance and
resistance training.  Determine relationship between exercise
patterns and degenerative joint diseases, such as osteoarthritis.
Establish possible mechanisms for prevention of bone diseases
including osteoporosis.
6.  Healing - Improved general understanding of the natural healing
process for muscle, bones, and connective tissue.  Determine what
interventions are most successful in enhancing healing and under what
conditions should these therapies are applied.  Establish the role of
cytokines in inflammation and healing.  Investigate healing from
localized tissue damage as a preliminary step in strengthening and/or
enlarging muscle and other connective tissue.
7.  Circulation - Improved understanding of changes in circulation
within the musculoskeletal system in response to patterns of use.
This announcement encourages studies on the mechanisms involved in
altered micro-vasculature and extra-vascular circulation in muscle,
bone, and joints. Investigators should explore differences due to
endurance and resistance training.
8.  Fitness and Wellness - Determine how molecular responses differ
depending on demands of endurance and resistance training.  Provide
improved understanding of how musculoskeletal activity leads to
general body fitness.  This would include homeostasis of the immune,
endocrine, and neuroendocrine systems. Explore how exercise patterns
affect different components of the immune system, determining
molecular mediators.
9.  Fitness and Nutrition - Explore how regular exercise effects body
need and use of nutrients. Study how patterns of musculoskeletal
activity differentially alter body allocation of metabolites and
energy supplies, exploring intercellular and inter tissue
communications.  Study the role of nutrition and dietary supplements
in improving performance and reducing fatigue.
10.  Clinical Studies - Provide improved repair and replacement of
injured muscle, connective tissues and joints.  Characterize
improvements in materials and methods for transplantation,
augmentation, and replacement of ligaments and tendons.  Common
sports injuries and symptoms include ligaments of the knee (such as
anterior cruciate ligaments and medial collateral ligaments),
patellar pain, and rotator cuff syndrome.  Study surgical and
non-surgical treatments, including rehabilitation modalities.
11.  Junctional Assessment and Gait Analysis - Establish simple,
quantitative measures of joint motion and forces that may be
uniformly applied at most research and clinical sites.  Document the
use of such evaluations for improved pre-injury screening and
post-injury surveillance.
12.  Epidemiology - Define the incidence and natural history of
injury in competitive sports and recreational activities.  Establish
risk factors for incurring injuries and for the progression of an
injury to a more serious medical problem.  Determine relationships
between sequential chronic and acute injuries.
13.  Prevention and Training - Develop improved protective sporting
equipment and training methods, especially for high risk competitive
and recreational activities.  Determine the short and long range
benefits and side-effects from using anabolic steroids and other
chemical enhancers of performance.  Establish more completely the
interrelations between neuromuscular and connective tissue response
to training.
Applications of interest to the NCMRR/NICHD should be related to
issues of musculoskeletal fitness, exercise physiology, and sports
medicine relevant to people with physical disabilities. Especially
encouraged are basic and clinical studies that will lead to the
development of rehabilitation interventions to enhance physical
fitness, prevent further disability through overuse injuries, and
lead to greater independence and physical functioning.
NINR is interested in related research on musculoskeletal fitness and
physical activity across the age continuum, especially studies on:
exercise and primary prevention, body fitness and wellness, and
clinical studies that test interventions that influence patient
health outcomes and reduce costs and demand for care.
It is the policy of the NIH that women and members of minority groups
and their sub- populations must be included in all NIH supported
biomedical and behavioral research projects involving human subjects,
unless a clear and compelling rationale and justification is provided
that inclusion is inappropriate with respect to the health of the
subjects or the purpose of the research.  This policy results from
the NIH Revitalization Act of 1993 (Section 492B of Public Law
103-43) and supersedes and strengthens the previous policies.
All investigators proposing research involving human subjects should
read the "NIH Guidelines for Inclusion of Women and Minorities as
Subjects in Clinical Research," which have been published in the
Federal Register of March 28, 1994 (FR 59 14508-14513) and reprinted
in the NIH Guide for Grants and Contracts, Volume 23, Number 11,
March 18, 1994.
Investigators also may obtain copies of the policy from the program
staff listed under INQUIRIES.  Program staff may also provide
additional relevant information concerning the policy.
Submit applications on the grant application form PHS 398 (rev.
5/95); applications will be accepted at the standard receipt
deadlines shown.  Application kits are available at most
institutional offices of sponsored research and may be obtained from
the Division of Extramural Outreach and Information Resources,
National Institutes of Health, 6701 Rockledge Drive, MSC 7910,
Bethesda, MD 20892-7910, telephone 301/710-0267; email:
ASKNIH@odrockm1.od.nih.gov.  The number (PA-97-025) and title
typed in Section 2 on the face page of the application.
The completed original application and five legible copies must be
sent or delivered to:
6701 ROCKLEDGE DRIVE, ROOM 1040 - MSC 7710
BETHESDA, MD  20892-7710
BETHESDA, MD  20817-7710 (for express/courier service)
Applications will be assigned on the basis of established PHS
referral guidelines.  Applications that are complete will be reviewed
in accordance with the usual NIH peer review procedures for research
grants (Study Section).  Following scientific-technical review, the
applications will receive a second-level review by the appropriate
national advisory council.
Review Criteria for Research Grants
o  Scientific, technical, or medical significance and originality of
the proposed research;
o  Appropriateness and adequacy of the experimental approach and
methodology proposed to carry out the research;
o  Qualifications and research experience of the Principal
Investigator and staff, particularly, but not exclusively, in the
area of the proposed research;
o  Availability of the resources necessary to perform the research;
o  Appropriateness of the proposed budget and duration in relation to
the proposed research;
o  Adequacy of plans to include both genders and minorities and their
subgroups as appropriate for the scientific goals of the research.
Plans for the recruitment and retention of subjects will also be
The initial review group will also examine the provisions for the
protection of human and animal subjects, and the safety of the
research environment.
Review Criteria for Career Awards
o  Quality of the candidate's academic and clinical record,
o  Potential to develop as an independent researcher;
o  Commitment to a research career; and
o  Likelihood that the plan will contribute substantially to the
achievement of scientific
Career Development Plan
o  Likelihood that the career development plan will contribute
substantially to the scientific development of the candidate;
o  Appropriateness of the content, the phasing, and the proposed
duration of the career
development plan for achieving scientific independence;
o  Consistency of the career development plan with the candidate's
career goals; and
o  Quality of the proposed training in responsible conduct of
Research Plan
Reviewers recognize that an individual with limited research
experience is less likely to be able to prepare a research plan with
the breadth and depth of that submitted by a more experienced
investigator.  Although it is understood that K08 applications do not
require the level of detail necessary in regular research grant
proposals, a fundamentally sound research plan must be provided.  In
general, less detail is expected with regard to research planned for
the later years of the award, but the application should outline the
general goals for these years.
o  Appropriateness of the research plan to the stage of research
development and as a vehicle for developing the research skills as
described in the career development plan;
o  Scientific and technical merit of the research question, design
and methodology;
o  Relevance of the proposed research to the candidate's career
objectives; and
o  Adequacy of the plan's attention to gender and minority issues.
o  Appropriateness of mentor's research qualifications in the area of
this application;
o  Quality and extent of mentor's proposed role in providing guidance
and advice to the candidate;
o  Previous experience in fostering the development of researchers;
o  History of research productivity and support.
Environment and Institutional Commitment
o  Applicant institution's commitment to the scientific development
of the candidate and assurances that the institution intends the
candidate to be an integral part of its research program;
o  Adequacy of research facilities and training opportunities;
o  Quality and relevance of the environment for scientific and
professional development of the candidate; and
o  Applicant institution's commitment to an appropriate balance of
research and clinical
Applications recommended by a National Advisory Council will be
considered for funding on the basis of overall scientific and
technical merit, program needs and balance, and availability of
For further information about programs in the National Institute of
Arthritis and Musculoskeletal and Skin Diseases, investigators are
encouraged to contact:
Richard W. Lymn, Ph.D.
Muscle Biology and Musculoskeletal Fitness Program Director
National Institute of Arthritis and Musculoskeletal and Skin Diseases
Natcher Building Room 5AS 49E
Bethesda, Maryland  20892-6500
Telephone:     (301)594-5128
FAX:           (301)480-4543
e-mail:        lymnr@ep.niams.nih.gov
Investigators concerned with orthopedic studies are encouraged to
James S. Panagis, M.D.
Orthopedics Program Director
National Institute of Arthritis and Musculoskeletal and Skin Diseases
Natcher Building Room 5AS 37K
Bethesda, Maryland  20892-6500
Telephone:      (301)594-5055
FAX:       (301)480-4543
e-mail:        panagisj@ep.niams.nih.gov
For information about support by the National Center for
Rehabilitation Research, contact:
Danuta Krotoski, Ph.D.
National Center for Medical Rehabilitation Research
National Institute of Child Health and Human Development
Building 61E, Room 2A-03
Bethesda, MD  20893-7510
Telephone:  (301) 402-2242
Email:  krotoskd@hd01.nichd.nih.gov
For information concerning research interests of the National
Institute of Nursing Research,
J. Taylor Harden, PhD, RN
Division of Extramural Programs
National Institute of Nursing Research
Building 45, Room 3AN-12
45 Center Drive, MSC 6300
Bethesda, MD  20892-6300
Telephone:  (301) 594-5976
FAX:  (301) 480-8260
Email:  THARDEN@ep.ninr.nih.gov
Direct inquiries regarding fiscal matters to:
Ms. Sally A. Nichols
National Institute of Arthritis and Musculoskeletal and Skin Diseases
Natcher Building, Room 5 AS 49F
Bethesda, MD  20892-6500
Telephone:  (301) 594-3535
FAX:  (301) 480-5450
Email:  nicholss@ep.niams.nih.gov
Ms. Mary Ellen Colvin
National Institute of Child Health and Human Development
Building 61E, Room 8A-17
Bethesda, MD 20892-7510
Telephone:  (301) 496-1303
E-mail:  colvinm@hd01.nichd.nih.gov
Jeff Carow
Grants and Contracts Management Branch
National Institute of Nursing Research
Building 45, Room 3AN-32
Bethesda, MD  20892-6301
Telephone:  (301) 594-5074
FAX:  (301) 480-8256
Email:  JCAROW@ep.ninr.nih.gov
These programs are described in the Catalog of Federal Domestic
Assistance No. 93.846, (Arthritis, Musculoskeletal and Skin Diseases
Research), No. 93.929 (Medical Rehabilitation Research,) and No.
93.361 (Nursing Research).  Awards will be made under the authority
of the Public Health Service Act, Title III, Section 301 (Public Law
410, 78th Congress, as amended, 42 USC 241) and administered under
PHS grants policies and Federal regulations 42 CFR Part 52 and 45 CFR
Part 74.  This program is not subject to the intergovernmental review
requirements of Executive Order 12372 or Health Systems Agency
The PHS strongly encourages all grant and contract recipients to
provide a smoke-free workplace and promote the non-use of all tobacco
products.  In addition, Public Law 103-227, the Pro-Children Act of
1994, prohibits smoking in certain facilities (or in some cases, any
portion of a facility) in which regular or routine education,
library, day care, health care or early childhood development
services are provided to children.  This is consistent with the PHS
mission to protect and advance the physical and mental health of the
American people.

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