Dietary Isoflavone-Dependent and Estradiol Replacement Effects on Body Weight in the Ovariectomized (OVX) Rat.

17ß-Estradiol is known to regulate energy metabolism and body weight. Ovariectomy results in body weight gain while estradiol administration results in a reversal of weight gain. Isoflavones, found in rodent chow, can mimic estrogenic effects making it crucial to understand the role of these compounds on metabolic regulation. The goal of this study is to examine the effect of dietary isoflavones on body weight regulation in the ovariectomized rat. This study will examine how dietary isoflavones can interact with estradiol treatment to affect body weight. Consistent with previous findings, animals fed an isoflavone-rich diet had decreased body weight (p<0.05), abdominal fat (p<0.05), and serum leptin levels (p<0.05) compared to animals fed an isoflavone-free diet. Estradiol replacement resulted in decreased body weight (p<0.05), abdominal fat (p<0.05), and serum leptin (p<0.05). Current literature suggests the involvement of cytokines in the inflammatory response of body weight gain. We screened a host of cytokines and chemokines that may be altered by dietary isoflavones or estradiol replacement. Serum cytokine analysis revealed significant (p<0.05) diet-dependent increases in inflammatory cytokines (keratinocyte-derived chemokine). The isoflavone-free diet in OVX rats resulted in the regulation of the following cytokines and chemokines: interleukin-10, interleukin-18, serum regulated on activation, normal T cell expressed and secreted, and monocyte chemoattractant protein-1 (p<0.05). Overall, these results reveal that estradiol treatment can have differential effects on energy metabolism and body weight regulation depending on the presence of isoflavones in rodent chow.

Traumatic brain injury clinical practice guidelines and best practices from the VA state of the art conference.

Management of symptoms following traumatic brain injury (TBI) can be complex and remains a high priority for Department of Defense (DoD) and Department of Veteran Affairs (VA). Concurrently, awareness of TBI in the public has increased. VA convened a State of the Art (SOTA) Conference to identify priorities for future research and promote best practices for TBI care. Scientific evidence of effective management of symptoms following TBI is expanding, and this evidence has been synthesized into Clinical Practice Guidelines (CPGs) and Clinical Practice Recommendations (CPRs). Knowledge gaps still exist and research efforts to address these gaps should include leveraging large administrative data sets and existing registries to determine effective treatments, investigate compliance of existing clinical care with CPGs and study limitations to determine modifiable vs. non-modifiable core tenants of the evidence-based treatments.

Concussion in the Military: an Evidence-Base Review of mTBI in US Military Personnel Focused on Posttraumatic Headache.

Traumatic brain injury (TBI) is defined as an alteration in brain function caused by an external force. Mild TBI or concussion is now well recognized to be a risk of military service as well as participation in athletic sports such as football. Posttraumatic headache (PTH) is the most common symptom after mTBI in US service members. PTH most commonly presents with migraine-like headache features. The following is an overview of the epidemiology, pathophysiology, clinical course, prognosis, complications, and treatment of mTBI and associated comorbidities with a focus on PTH. There is a particular emphasis on emerging evidence-based clinical practice. One important medical consequence of the recognition that mTBI is a highly prevalent among military service members is that the Department of Defense (DoD) is dedicating significant financial and intellectual resources to better understanding and developing treatments for TBI. The identification of the importance of TBI among the US military population has had the added benefit of increasing awareness of this condition among civilian populations, particularly those engaged in both professional and youth sports. The NIH and NSF are also supporting important TBI research. President Obama's Brain Initiative is also providing additional impetus for these efforts. Unfortunately, the understanding of the acute and chronic effects of mTBI on the brain remains limited. Gratefully, there is hope that through innovative research, there will be advances in elucidating the underlying pathophysiology, which will lead to clinical and prognostic indicators, ultimately resulting in new treatment options for this very complicated set of disorders.

Neuralgic amyotrophy manifested by severe axillary mononeuropathy limited only to the anterior branch.

INTRODUCTION: In this study we describe a case demonstrating clinical, radiographic, electrophysiologic, and surgical evidence of a restricted but severe anterior branch axillary nerve mononeuropathy due to neuralgic amyotrophy (NA). METHODS: On each diagnostic modality there was severe involvement of the anterior and lateral deltoid muscle with sparing of the posterior deltoid and teres minor muscles and cutaneous innervation to the skin overlying the lateral shoulder. RESULTS: No structural etiologies were discovered during surgical exploration. CONCLUSIONS: This case provides another unique manifestation of NA and augments the theory of selective fascicular vulnerability.

Pathophysiology of battlefield associated traumatic brain injury.

As more data is accumulated from Operation Iraqi Freedom and Operation Enduring Freedom (OEF in Afghanistan), it is becoming increasing evident that traumatic brain injury (TBI) is a serious and highly prevalent battle related injury. Although traditional TBIs such as closed head and penetrating occur in the modern battle space, the most common cause of modern battle related TBI is exposure to explosive blast. Many believe that explosive blast TBI is unique from the other forms of TBI. This is because the physical forces responsible for explosive blast TBI are different than those for closed head TBI and penetrating TBI. The unique force associated with explosive blast is the blast shock pressure wave. This shock wave occurs over a very short period, milliseconds, and has a specific profile known as the Freidlander curve. This pressure-time curve is characterized by an initial very rapid up-rise followed by a longer decay that reaches a negative inflection point before returning to baseline. This is important as the effect of this shock pressure on brain parenchyma is distinct. The diffuse interaction of the pressure wave with the brain leads to a complex cascade of events that affects neurons, axons, glia cells, and vasculature. It is only by properly studying this disease will meaningful therapies be realized.

Mild traumatic brain injury screening, diagnosis, and treatment.

The majority of combat-related traumatic brain injury (TBI) within the U.S. Armed Forces is mild TBI (mTBI). This article focuses specifically on the screening, diagnosis, and treatment aspects of mTBI within the military community. Aggressive screening measures were instituted in 2006 to ensure that the mTBI population is identified and treated. Screenings occur in-theater, outside the contiguous United States, and in-garrison. We discuss specific screening procedures at each screening setting. Current diagnosis of mTBI is based upon self-report or through witnesses to the event. TBI severity is determined by specific Department of Defense criteria. Abundant clinician resources are available for mTBI in the military health care setting. Education resources for both the patient and the clinician are discussed in detail. An evidence-based clinical practice guideline for the care of mTBI was created through collaborative efforts of the DoD and the U.S. Department of Veterans Affairs. Although symptoms following mTBI generally resolve with time, active treatment is centered on symptom management, supervised rest, recovery, and patient education. Medical specialty care, ancillary services, and other therapeutic services may be required.

Explosive-driven double-blast exposure: molecular, histopathological, and behavioral consequences.

Traumatic brain injury generated by blast may induce long-term neurological and psychiatric sequelae. We aimed to identify molecular, histopathological, and behavioral changes in rats 2 weeks after explosive-driven double-blast exposure. Rats received two 30-psi (~ 207-kPa) blasts 24 h apart or were handled identically without blast. All rats were behaviorally assessed over 2 weeks. At Day 15, rats were euthanized, and brains removed. Brains were dissected into frontal cortex, hippocampus, cerebellum, and brainstem. Western blotting was performed to measure levels of total-Tau, phosphorylated-Tau (pTau), amyloid precursor protein (APP), GFAP, Iba1, αII-spectrin, and spectrin breakdown products (SBDP). Kinases and phosphatases, correlated with tau phosphorylation were also measured. Immunohistochemistry for pTau, APP, GFAP, and Iba1 was performed. pTau protein level was greater in the hippocampus, cerebellum, and brainstem and APP protein level was greater in cerebellum of blast vs control rats (p < 0.05). GFAP, Iba1, αII-spectrin, and SBDP remained unchanged. No immunohistochemical or neurobehavioral changes were observed. The dissociation between increased pTau and APP in different regions in the absence of neurobehavioral changes 2 weeks after double blast exposure is a relevant finding, consistent with human data showing that battlefield blasts might be associated with molecular changes before signs of neurological and psychiatric disorders manifest.

Total intravenous anesthesia including ketamine versus volatile gas anesthesia for combat-related operative traumatic brain injury.

BACKGROUND: Traumatic brain injury is a leading cause of death and severe neurologic disability. The effect of anesthesia techniques on neurologic outcomes in traumatic brain injury and potential benefits of total intravenous anesthesia (TIVA) compared with volatile gas anesthesia (VGA), although proposed, has not been well evaluated. The purpose of this study was to compare TIVA versus VGA in patients with combat-related traumatic brain injury. METHODS: The authors retrospectively reviewed 252 patients who had traumatic brain injury and underwent operative neurosurgical intervention. Statistical analyses, including propensity score and matched analyses, were performed to assess differences between treatment groups (TIVA vs. VGA) and good neurologic outcome. RESULTS: Two hundred fourteen patients met inclusion criteria and were analyzed; 120 received VGA and 94 received TIVA. Good neurologic outcome (Glasgow Outcome Score 4-5) and decreased mortality were associated with TIVA compared with VGA (75% vs. 54%; P = 0.002 and 5% vs. 16%; P = 0.02, respectively). Multivariate logistic regression found admission Glasgow Coma Scale score of 8 or greater (odds ratio, 13.3; P < 0.001) and TIVA use (odds ratio, 2.3; P = 0.05) to be associated with good neurologic outcomes. After controlling for confounding factors using propensity analysis and repeated one-to-one matching of patients receiving TIVA with those receiving VGA with regard to Injury Severity Score, Glasgow Coma Scale score, base deficit, Head Abbreviated Injury Score, and craniectomy or craniotomy, the authors could not find an association between treatment and neurologic outcome. CONCLUSION: Total intravenous anesthesia often including ketamine was not associated with improved neurologic outcome compared with VGA. Multiple confounders limit conclusions that can be drawn from this retrospective study.

MRI in Management of Mild TBI/Concussion in the Deployed Setting.

Magnetic resonance imaging (MRI) has specific limitations in theater and has unique requirements for its safe use with patients which require additional technician training and strict adherence to MRI-specific safety protocols. Neuroimaging is recommended for the evaluation of service members with clinical red flags new onset or persistent or worsening symptoms, and individuals whose recovery is not progressing as anticipated. This article is a brief discussion of when MRI is appropriate.