Association of Gastrointestinal Distress in Ultramarathoners with Race Diet

Context: Gastrointestinal (GI) distress is common during ultrarunning. Purpose: To determine if race diet is related to GI distress in a 161-km ultramarathon. Methods: Fifteen (10 male, 5 female) consenting runners in the Javelina Jundred (6.5 loops on a desert trail) participated. Body mass was measured immediately pre-race and after each loop. Runners reported if they had nausea, vomiting, abdominal cramps, and/or diarrhea after each loop. Subjects were interviewed after each loop to record food, fluid, and electrolyte consumption. Race diets were analyzed using Nutritionist Pro. Results: Nine (8 male, 1 female) of 15 runners experienced GI distress including nausea (89%), abdominal cramps (44%), diarrhea (44%), and vomiting (22%). Fluid consumption rate was higher (p = .001) in runners without GI distress (10.9 ± 3.2 ml · kg–1 · hr–1) than in those with GI distress (5.9 ± 1.6 ml · kg–1 · hr–1). Runners without GI distress consumed a higher percentage fat (p = .03) than runners with GI distress (16.5 ± 2.6 vs. 11.1 ± 5.0). In addition, fat intake rate was higher (p = .01) in runners without GI distress (0.06 ± 0.03 g · kg–1 · hr–1) than in runners with GI distress (0.03 ± 0.01 g · kg–1 · hr–1). Lower fluid and fat intake rates were evident in those developing GI distress before the onset of symptoms. Conclusions: A race diet with higher percentage fat and higher intake rates of fat and fluid may protect ultramarathoners from GI distress. However, these associations do not indicate cause and effect, and factors other than race diet may have contributed to GI distress

Bone: An Acute Buffer of Plasma Sodium during Exhaustive Exercise?

Both hyponatremia and osteopenia separately have been well documented in endurance athletes. Although bone has been shown to act as a “sodium reservoir” to buffer severe plasma sodium derangements in animals, recent data have suggested a similar function in humans. We aimed to explore if acute changes in bone mineral content were associated with changes in plasma sodium concentration in runners participating in a 161 km mountain footrace. Eighteen runners were recruited. Runners were tested immediately pre- and post-race for the following main outcome measures: bone mineral content (BMC) and density (BMD) via dual-energy X-ray absorptiometry (DEXA); plasma sodium concentration ([Na+]p), plasma arginine vasopressin ([AVP]p), serum aldosterone concentration ([aldosterone]s), and total sodium intake. Six subjects finished the race in a mean time of 27.0±2.3 h. All subjects started and finished the race with [Na+]p within the normal range (137.7±2.3 and 136.7±1.6 mEq/l, pre- and post-race, respectively). Positive correlations were noted between change (Δ; post-race minus pre-race) in total BMC (grams) and [Na+]p (mEq/l) (r=0.99;

Exposures to the environmental toxicants pentachlorophenol (PCP) and dichlorodiphenyltrichloroethane (DDT) modify secretion of interleukin 1-beta (IL-1β) from human immune cells

Pentachlorophenol (PCP) and Dichlorodiphenyltrichloroethane (DDT) are environmental contaminants found in human blood. Previous studies have shown that PCP and DDT inhibit the lytic function of highly purified human natural killer (NK) lymphocytes and decrease the expression of several surface proteins on NK cells. Interleukin-1 βeta (IL-1β) is a cytokine produced by lymphocytes and monocytes, and anything that elevates its levels inappropriately can lead to chronic inflammation, which among other consequences can increase tumor development and invasiveness. Here, PCP and DDT were examined for their ability to alter secretion of IL-1β from immune cell preparations of various complexity: NK cells; monocyte-depleted (MD) peripheral blood mononuclear cells (PBMCS); and PBMCs. Cells were exposed to concentrations of PCP ranging from 5 to 0.05 µM and DDT concentrations of 2.5–0.025 μM for 24, 48 h, and 6 days. Results showed that both PCP and DDT increased IL-1β secretion from all of the immune cell preparations. The specific concentrations of PCP and DDT that increased IL-1β secretion varied by donor. Immune cells from all donors showed compound-induced increases in IL-1β secretion at one or more concentration at one or more length of exposure. The mechanism of PCP stimulation of IL1-β secretion was also addressed, and it appears that the MAPKs, ERK1/2 and p38, may be utilized by PCP to stimulate secretion of IL-1β

Hyponatremia in the 2009 161-km Western States Endurance Run

Purpose:To determine the incidence of exercise-associated hyponatremia (EAH), the associated biochemical measurements and risk factors for EAH, and whether there is an association between postrace blood sodium concentration ([Na+]) and changes in body mass among participants in the 2009 Western States Endurance Run, a 161-km mountain trail run. Methods: Change in body mass, postrace [Na+], and blood creatine phosphokinase (CPK) concentration, and selected runner characteristics were evaluated among consenting competitors. Results: Of the 47 study participants, 14 (30%) had EAH as defined by a postrace [Na+] /L. Postrace [Na+] and percent change in body mass were directly related (r = .30, P = .044), and 50% of those with EAH had body mass losses of 3–6%. EAH was unrelated to age, sex, finish time, or use of nonsteroidal anti-inflammatory drugs during the run, but those with EAH had completed a smaller (P = .03) number of 161-km ultramarathons. The relationship of CPK levels to postrace [Na+] did not reach statistical significance (r = –.25, P = .097). Conclusions: EAH was common (30%) among finishers of this 161-km ultramarathon and it was not unusual for those with EAH to be dehydrated. As such, changes in body mass should not be relied upon in the assessment for EAH during 161-km ultramarathons

Exposures to the Environmental Contaminants Pentachlorophenol (PCP) and Dichlorodiphenyltrichloroethane (DDT) Increase Production of the Pro-inflammatory cytokine, Interleukin 1-Βeta (IL-1β), in Human Immune Cells

Pentachlorophenol (PCP) and dichlorodiphenyltrichloroethane (DDT), are organochlorine environmental contaminants found in human blood at very significant levels (as high as 5 µM for PCP and 260 nM for DDT). Cancers of the blood (lymphoma and myeloma) and kidney as well as others have been associated with exposure to these contaminants. Interleukin 1 beta (IL-1β) is a pro-inflammatory cytokine and is involved in stimulating cell proliferation. High levels of IL-1β are associated with inflammatory diseases and tumor progression. Previous studies showed that PCP and DDT at certain concentrations were able to stimulate secretion of IL-1β. This study shows that the increased secretion of IL-1β seen with both contaminants is due to compound-induced increases in production of this cytokine. Increased production began within 6 h of exposure to PCP and continued to increase out to 24 h. DDT-induced stimulation of IL-1β appeared to be maximal after 6 h of exposure and then diminished by 24 h. The increases seen in IL-1β production stimulated by PCP appear to be at least partially due to compound-induced increases in IL-1β mRNA. Although DDT caused increased production of IL-1β, it did not appear to cause consistent increases in its mRNA. PCP-and DDT-induced increases in IL-1β production were dependent primarily on the p38 MAPK pathway. These results indicate that both PCP and DDT are able to increase IL1-β production in a p38 MAPK dependent manner, which may have the potential to influence chronic inflammation

Existential behavioral therapy for informal caregivers of palliative patients: Barriers and promoters of support utilization

AbstractObjective:Several interventions have been developed during recent years to support informal caregivers of palliative patients. However, these trials reported low enrollment rates. Employing a newly developed group intervention, existential behavioral therapy (EBT), one study reported that only 13.6% of approached informal caregivers participated. The purpose of our present study was to identify the reasons for this low enrollment rate in order to improve future support designs.Method:All participants in the EBT trial (intervention vs. standard-care control group) as well as those who declined participation during a 4-month recruitment period were studied prospectively over 12 months. Andersen's behavioral model of healthcare service use was employed to identify group differences between acceptors and decliners: predisposing (age, gender, education, family status, relationship), enabling (social support, distance to hospital, caring vs. bereaved), and need factors (psychological distress, quality of life) were evaluated in a binary-logistic model.Results:Some 94 decliners were compared to 160 EBT participants (n = 81 intervention, n = 79 control). Caregivers who took part were significantly more distressed and suffered from a lower quality of life compared to decliners. Not only these need factors but also predisposing (age &lt;55 years) and enabling (use of social/professional support, familiarity with caregiving institution) factors were associated with EBT utilization. At the 12-month follow-up, EBT intervention participants reported greater quality of life improvements than decliners or controls (p = 0.05). While all groups had mean anxiety scores below the cutoff at 12-month follow-up, decliners showed better improvement in anxiety compared to EBT participants (intervention p = 0.04, controls p = 0.03).Significance of results:On average, decliners are less burdened: they may be more resilient, may have better coping strategies, or already have a sufficient support network in place. Screening caregivers with regard to their experienced quality of life and targeting those in need, especially younger caregivers with low levels of quality of life, may help to allocate resources more appropriately.</jats:sec

Differential effects of selective inhibitors targeting the PI3K/AKT/mTOR pathway in acute lymphoblastic leukemia

Purpose: Aberrant PI3K/AKT/mTOR signaling has been linked to oncogenesis and therapy resistance in various malignancies including leukemias. In Philadelphia chromosome (Ph) positive leukemias, activation of PI3K by dysregulated BCR-ABL tyrosine kinase (TK) contributes to the pathogenesis and development of resistance to ABL-TK inhibitors (TKI). The PI3K pathway thus is an attractive therapeutic target in BCR-ABL positive leukemias, but its role in BCR-ABL negative ALL is conjectural. Moreover, the functional contribution of individual components of the PI3K pathway in ALL has not been established. Experimental design: We compared the activity of the ATP-competitive pan-PI3K inhibitor NVP-BKM120, the allosteric mTORC1 inhibitor RAD001, the ATP-competitive dual PI3K/mTORC1/C2 inhibitors NVP-BEZ235 and NVP-BGT226 and the combined mTORC1 and mTORC2 inhibitors Torin 1, PP242 and KU-0063794 using long-term cultures of ALL cells (ALL-LTC) from patients with B-precursor ALL that expressed the BCR-ABL or TEL-ABL oncoproteins or were BCR-ABL negative. Results: Dual PI3K/mTOR inhibitors profoundly inhibited growth and survival of ALL cells irrespective of their genetic subtype and their responsiveness to ABL-TKI. Combined suppression of PI3K, mTORC1 and mTORC2 displayed greater antileukemic activity than selective inhibitors of PI3K, mTORC1 or mTORC1 and mTORC2. Conclusions: Inhibition of the PI3K/mTOR pathway is a promising therapeutic approach in patients with ALL. Greater antileukemic activity of dual PI3K/mTORC1/C2 inhibitors appears to be due to the redundant function of PI3K and mTOR. Clinical trials examining dual PI3K/mTORC1/C2 inhibitors in patients with B-precursor ALL are warranted, and should not be restricted to particular genetic subtypes

The organochlorine pesticides pentachlorophenol and dichlorodiphenyltrichloroethane increase secretion and production of interleukin 6 by human immune cells

The environmental contaminants pentachlorophenol (PCP) and 4, 4′-dichlorodiphenyltrichloroethane (DDT) are detected in some human blood samples at levels as high as 5 μM (PCP) and 260 nM (DDT). Several cancers are associated with exposures to these contaminants. IL-6 is a pro-inflammatory cytokine that when dysregulated stimulates inflammatory diseases and tumor progression. Immune cells exposed to PCP at 0.05–5 μM and DDT at 0.025–2.5 μM showed increased secretion of IL-6 when the cell preparations contained either T lymphocytes or monocytes. Increased IL-6 secretion was due to PCP and DDT induced cellular production of the cytokine and was dependent on MAP kinase signaling pathways (in the case of PCP). Compound-induced increases in IL-6 production were in part due to increases in either the transcription of and/or stability of its mRNA. Thus, both PCP and DDT have the potential to produce chronic inflammation by stimulating production of IL-6 by immune cells

Statement of the Third International Exercise-Associated Hyponatremia Consensus Development Conference, Carlsbad, California, 2015

The third International Exercise-Associated Hyponatremia (EAH) Consensus Development Conference convened in Carlsbad, California in February 2015 with a panel of 17 international experts. The delegates represented 4 countries and 9 medical and scientific sub-specialties pertaining to athletic training, exercise physiology, sports medicine, water/sodium metabolism, and body fluid homeostasis. The primary goal of the panel was to review the existing data on EAH and update the 2008 Consensus Statement.1 This document serves to replace the second International EAH Consensus Development Conference Statement and launch an educational campaign designed to address the morbidity and mortality associated with a preventable and treatable fluid imbalance. The following statement is a summary of the data synthesized by the 2015 EAH Consensus Panel and represents an evolution of the most current knowledge on EAH. This document will summarize the most current information on the prevalence, etiology, diagnosis, treatment and prevention of EAH for medical personnel, athletes, athletic trainers, and the greater public. The EAH Consensus Panel strove to clearly articulate what we agreed upon, did not agree upon, and did not know, including minority viewpoints that were supported by clinical experience and experimental data. Further updates will be necessary to both: (1) remain current with our understanding and (2) critically assess the effectiveness of our present recommendations. Suggestions for future research and educational strategies to reduce the incidence and prevalence of EAH are provided at the end of the document as well as areas of controversy that remain in this topic. [excerpt