Heat Tolerance Testing and the Return to Duty Decision: A Two-Year Case Cohort Analysis.

BACKGROUND: Among individuals with prior exertional heat illness (EHI), heat tolerance testing (HTT) may inform risk and return to duty/activity. However, little is known about HTT's predictive validity, particularly for EHI recurrence. Our project sought to demonstrate the predictive validity of HTT in EHI recurrence and HTT's utility as a diagnostic tool in exertional heat stroke (EHS). METHODS: Participants with prior EHS were recruited for the study by a physician's referral and were classified as heat tolerant or intolerant after completing demographics and an HTT. Participants were further categorized as single/simple (SS) EHI or recurrent/complex (RC) EHI by conducting a retrospective record review of the following two years. We calculated the positive (PPV) and negative predictive values (NPV) of HTT. RESULTS: The retrospective review of HTT records was used to categorize 44% of Servicemembers as RC, with 77% classified as heat tolerant, 14% as heat intolerant, and 9% as borderline. When borderline cases were classified as heat intolerant, HTT had a high NPV, indicating a high probability that heat-tolerant individuals did not have recurrent EHI. When borderline cases were classified as heat tolerant, NPV and sensitivity decreased while specificity increased. CONCLUSION: We demonstrated that the HTT had a 100% NPV for future EHI over two years of follow-up for Servicemembers with a history of recurrent heat injury and negative HTT results. An HTT can provide critical data points to inform return to duty decisions and timelines by predicting the risk of EHI recurrence.

Effects of training service dogs on service members with PTSD: A pilot-feasibility randomized study with mixed methods.

This pilot-feasibility randomized control trial examined effects of an adjunctive short-term service dog training program (SDTP) for service members in out-patient treatment for PTSD. Twenty-nine volunteer participants were randomly assigned to either the SDTP (n = 12) or waitlist (n = 17); 20 participants were available for post-treatment evaluation. SDTP protocol consisted of six structured one-hour sessions with a dog-trainer conducted over two weeks, intended to train a service dog to help a fellow Veteran. SMs completed symptom questionnaires (PTSD, insomnia, stress, depression, anxiety), and the SDTP group completed a post-intervention quantitative interview. Most effect sizes demonstrated moderate symptom reductions, both between-groups and within the SDTP group. Between-group effects were strongest for intrusive thoughts (Hedge's g = -0.66; 95%CI: -1.72, 0.23) and overall PTSD symptoms (g = -0.45; 95%CI: -1.47, 0.45); within-SDTP group effects were strongest for stress (d = -1.31, 95%CI: -2.17, -0.42), intrusive thoughts (d = -0.78, 95%CI: -1.55, 0.01) and hypervigilance (d = -0.77, 95%CI: -1.48, -0.04). Qualitative analyses indicated participants found SDTP in some ways challenging yet beneficial in multiple aspects of personal and social lives. Future work should examine optimal treatment parameters (e.g., duration, "dosing") when training dogs as an adjunct to other PTSD treatment.

Perceptual strain in a compensable hot environment: Accuracy and clinical correlates.

Heat strain monitoring indexes are important to prevent exertional heat illness (EHI) and uncover risk factors. Two indexes are the Physiological Strain Index (PSI) and a subjective PSI analogue, the Perceptual Strain Index (PeSI). The PeSI is a feasible alternative to PSI in field conditions, although the validity has been variable in previous research. However, the PeSI has been rarely examined at a low heat strain with compensable heat stress, such as during a heat tolerance test (HTT). This study evaluated the discrepancy between the maximal PeSI and maximal PSI achieved during a HTT and determined their association with EHI risk factors, including history of EHI, percent body fat (%BF), relative VO2max, fatigue and sleep status (n = 121; 47 without prior EHI, 74 with prior EHI). The PSI was calculated using the change in rectal temperature (Tre) and heart rate (HR) and PeSI was calculated based on the formula containing thermal sensation (TS), a Tre analogue, and rate of perceived exertion (RPE), a HR analogue. Significant associations were identified between PSI and PeSI and between PSIHR and PeSIHR in the total sample and between PSI and PeSI in the EHI group. Bland-Altman analyses indicated PeSI underestimated PSI in the total sample, PSIHR was greater than PeSIHR, and that PSIcore and PeSIcore were not significantly different, but values varied widely at different heat strains. This indicates the use of RPE underestimates HR and that the accuracy of TS to predict Tre may be subpar. This study also demonstrated that participants with higher %BF have a decreased perception of heat strain and that post-fatigue, sleep status and a prior EHI may increase the perception of heat strain. Overall, these results suggest that PeSI is a poor surrogate for PSI in a compensable heat stress environment at low heat strain.

A nature-based health intervention at a military healthcare center: a randomized, controlled, cross-over study.

We describe a mixed qualitative and quantitative research study in a military facility regarding the role of nature in well-being. Study intervention included two 20-minute walks. One walk was in an intentionally designed woodland environment (Green Road) and the other was on a busy campus road in a medical treatment facility (Urban Road). Twelve volunteers from a military facility participated in both walks in a cross-over experimental design. The two walking sessions were randomly ordered and preceded by pre-walk instructions appropriate to each road's characteristics and incorporated focused attention and present moment orientation. A semi-structured post-walk interview, the primary outcome, was conducted after the conclusion of each walk. Qualitative data analyses consisted of sentiments and themes by using NVivo 12 software. The Green Road was unanimously rated as positive (100%). Responses to Urban Road were evenly distributed among positive (33.3%), negative (33.3%), and neutral/mixed (33.3%) sentiments. The Green Road yielded predominantly positive themes such as enjoyment of nature, relaxation, and feelings of privacy and safety. Urban Road produced significantly more negative themes such as concerns for safety, dislike of noise and other noxious experiences. Quantitative assessment of distress and mindfulness with Distress Thermometer (DT) and Mindful Attention Awareness Scale-state version (MAAS) demonstrated that a walk on the Green Road significantly decreased distress and increased mindfulness compared to a walk on the Urban Road. We also observed that pre-walk instructions could direct attention to both obvious and subtle elements of experience and enhance awareness. Results support the notion that an intentional nature-based environment may produce significantly more positive experiences and result in health-promoting benefits in a military health-care setting compared to an urban environment. Future studies with clinical populations could advance our understanding of the healing value of nature-based interventions. The impact of intentional green environments may be enhanced by well-designed instructions for both recreational and therapeutic use.

Gene expression profiling of humans under exertional heat stress: Comparisons between persons with and without exertional heat stroke.

Exertional heat stroke (EHS) is a leading cause of preventable morbidity and mortality among both athletes and warfighters. Therefore, it is important to find blood biomarkers to predict susceptibility to EHS. We compared gene expression profiling from blood cells between two groups of participants - those with and those without a history EHS - by using genome-wide microarray analysis. Subjects with a history of EHS (n = 6) and non-EHS controls without a history of EHS (n = 18) underwent a heat tolerance test and a thermoneutral exercise challenge on separate days. The heat tolerance test comprised of 2-h of walking, at 5 km/h and 2% incline, with ambient conditions set at 40 °C, 40% relative humidity; the thermoneutral test was similar, but had ambient conditions set at 22 °C. Next, we examined gene expression profiles, quantified based on arithmetic differences (post minus pre) during the heat test minus changes during the thermoneutral test. Genes related to interleukins and cellular stress were significantly down-regulated in participants with a history of EHS compared to their non-EHS counterparts. Suppression of these genes may be associated with susceptibility to exertional heat injury. Prospective research is required to determine whether similar gene expression profiling can be potentially used as blood biomarkers to predict susceptibility to EHS.

Army Combat Medic Resilience: The Process of Forging Loyalty.

This study presents a grounded theory analysis of in-depth interviews of United States Army Combat Medics (CMs) who had served in Iraq and/or Afghanistan. The study explores how 17 CMs nominated by their peers as resilient cope with military stressors in order to identify the factors that enable them to thrive amidst harsh conditions. Four distinct categories of characteristics unique to this group emerged: (1) social bonding, (2) readiness, (3) dual loyalty as performance, and (4) leader by example. Forging loyalty underpins these characteristics and represents the main process used by resilient CMs and comprised three behavior patterns: (1) commitment to the family, (2) commitment to the military mission, and (3) commitment to their guiding religious and spiritual beliefs. Prominent behavioral tendencies of forging loyalty likely developed during childhood and re-enforced by families, friends, and other role models. Based on the findings, new training and education efforts should focus on developing positive emotional, environmental, and social resources to enhance the health and well-being of service members and their families.

Oral manifestations in gastroesophageal reflux disease.

Many systemic diseases exert their influence on oral health. Among these, gastroesophageal reflux disease (GERD) is the most common. In this study, 100 patients who were previously diagnosed with GERD were examined following a 12-hour fast and evaluated in terms of the severity (grade) of the disease as well as any oral, dental, and/or salivary pH changes. Results found 11 patients with tooth erosion. These patients were older, and their average mean duration of GERD was longer in comparison to those without erosion. There was an inverse relationship between salivary pH and the GERD duration and grade of severity. As the GERD grade increased, the severity of tooth erosion increased. Patients with erosion also exhibited oral mucosal changes. Thus severe, long-term GERD was found to be potentially detrimental to oral soft tissues, dental structures, and salivary pH, whereas milder forms of the disease did not necessarily cause dental side effects.

Complex odontoma.

Odontomas are hamartomatous lesions or malformations composed of mature enamel, dentin, and pulp. They may be compound or complex, depending on the extent of morphodifferentiation or their resemblance to normal teeth. The etiology of odontoma is unknown, although several theories have been proposed. This article describes a case of a large infected complex odontoma in the residual mandibular ridge, resulting in considerable mandibular expansion.

Effect of fluidizing agents on paclitaxel penetration in cervical cancerous monolayer membranes.

The aim of this study was to compare modulation of paclitaxel penetration in cancerous and normal cervical monolayers by four fluidizing agents: PCPG (9:1 DPPC:PG), PCPE (9:1 DPPC:DOPE), ALEC (7:3 DPPC:PG) and Exosurf (13.5:1.5:1.0 DPPC:hexadecanol:tyloxapol). Presence of the fluidizing agents improved drug penetration significantly. PCPG and PCPE were promising penetration enhancers. PCPG 0.1% caused 3.8- and 1.7-fold higher maximum increments in surface pressure due to drug penetration, (Delta pi)(max), than the control in cancerous and normal monolayers, respectively, at 20 mN/m. In cancerous monolayer at 20 mN/m, presence of 0.1%, 0.5%, 1%, 5% and 10% PCPE produced 3.4-, 5.7-, 7.4-, 9.6- and 9.8-fold higher drug penetration compared to the control monolayer without PCPE, respectively. In cancerous monolayer at 20 mN/m, PCPG and PCPE liposomes having 1 mg lipid gave 2.1 and 3.6 times higher (Delta pi)(max )compared to the control, respectively. Further, the liposomal drug penetration was found to be directly proportional to the liposomal lipid content. The effect of the fluidizing agents was confirmed by increased calcein release from model cervical cancer liposomes. These results may have implications in using the above biocompatible lipids and surfactants as penetration enhancers along with anticancer drugs or as carriers for liposomal formulations of anticancer drugs for improved membrane penetration.

Effect of temperature on surface properties of cervical tissue homogenate and organic phase monolayers.

The temperature dependence of Langmuir monolayers of normal and cancerous human cervical tissues and their organic phases between temperatures of 37 and 45 degrees C was evaluated. Analysis of the surface pressure-area isotherms revealed significantly different increase in fluidity of the cancerous cervical tissue monolayer at 42 degrees C as opposed to the normal cervical tissue monolayers (p<0.05). Similarly, in the case of cervical cancerous organic phase monolayers significant increase of fluidity was observed at 40 degrees C whereas no such change was observed in the normal cervical organic phase monolayers. The effect of temperature was found to be different in cancerous and normal cervical tissues and this may be due to the different lipid profiles in them. Cancerous cervical tissues had 1.8-fold higher total lipids as compared to the normals. Similarly, the PC, PE, PI, PG, SM and PS levels in cancerous cervical tissues were 3.6, 2.0, 2.3, 4.7, 1.7 and 2.2 times higher than those of normal cervical tissues, respectively. Significant cancer-normal difference in minimum surface tension and hysteresis area was found at all temperatures studied for both tissue homogenates and organic phases. For example, cancerous tissue homogenates showed minimum surface tensions of 51.9+/-4.6, 54.4+/-5.9, 57.6+/-6.0 and 51.9+/-5.6mN/m at temperatures 37, 40, 42 and 45 degrees C whereas the corresponding values for normal cervical tissue homogenates were 39.3+/-3.6, 39.2+/-3.7, 39.2+/-3.8 and 39.1+/-3.6, respectively. The fluidity change at hyperthermic range of temperature can be correlated to the increased efficiency of drug on combination therapy with hyperthermia. These results may have implications in manipulating the fluidity of cervical cancer tissue membranes for better permeability thereby leading to better therapeutic strategies for cervical cancer.

Tensiometric profiles and their modulation by cholesterol: implications in cervical cancer.

Langmuir monolayers offer a convenient model for understanding the behavior of many natural systems like biological membranes. This technique was used to characterize the role of cholesterol, lipophilic, and lipophobic components of tissues in cervical cancer by evaluating their tensiometric profiles. Monolayers were formed on the surface of deionized water by spreading tissue components corresponding to 1 mg of the tissue for studying their surface pressure-area isotherms at body temperature. The cholesterol content of cancerous human cervical tissues was higher than that of the normal human cervical tissues. The addition of 3 mug cholesterol/mg tissue to the normal organic phase changed its tensiometric profile to that of the cancerous profile. Statistically significant tensiometric parameters showed that cholesterol acts as a rigidifier in the cervical tissues and has a remarkable role in shifting the normal cervical lipophilic surface activity towards that of the cancerous lipophilic monolayer. Several mixtures of the lipophilic-lipophobic components of both cancerous as well as normal cervical tissues also were characterized to reveal the relative contribution of these phases in the cervical cancer tensiometric profiles. Though the actual ratio of aqueous and organic phases in the normal tissue was 97:3 by weight, the tissue homogenate behavior was similar to that of a 50:50 mixture by weight, indicating the nonadditivity of the lipophilic-lipophobic components. The addition of cholesterol to a 97: 3 by weight aqueous: organic mixture of normal cervical tissue also revealed the rigidifying role of cholesterol. Unlike in normal tissue homogenates, the cancerous tissue homogenate tensiometric profile had more contribution from its aqueous phase components and an additive interaction between the lipophilic and lipophobic components was observed in the tissue homogenate. Thus, distinct differences in the interactions between lipophilic and lipophobic components were observed in cancerous and normal states. The Langmuir monolayer technique was sensitive to detect such changes in the form of altered tensiometric profiles. Therapeutic strategies may be designed to modulate these tensiometric profiles to our benefit.

Comparison of paclitaxel penetration in normal and cancerous cervical model monolayer membranes.

The aim of the present study was to evaluate the penetration of paclitaxel in normal as well as cancerous human cervical monolayer membranes and to compare these results with the paclitaxel penetration in a model dipalmitoylphosphatidylcholine (DPPC) monolayer. At physiologically relevant surface pressures of 30 mN/m, equilibrium drug penetration was observed in DPPC model membrane, whereas in cervical lipid model membranes exclusion of the drug and destabilization of the membrane was observed. The maximum surface pressure increment due to penetration (Deltapi(max)) of 600 nM paclitaxel, for DPPC monolayer was found to be 3.6, 5.4 and 5.0 times higher than those for penetration in the cancerous monolayer at surface pressures 10, 20 and 30 mN/m, respectively. At initial surface pressure 10 mN/m, the maximum surface pressure increment, for 600 nM paclitaxel penetration, of normal cervical lipid membrane was double that of the cancerous cervical lipid membrane. At 30 mN/m initial surface pressure the representative IC(50) concentration of the drug produced negligible drug penetration and significant membrane destabilization in cervical lipid model membranes. The difference in penetration profile could be due to differences in composition of the model membranes. The cholesterol level in cancerous cervical membrane was 1.5-folds higher than that in the normal cervical membrane. Apart from PC, another constituent present in 20-32% in cancerous and normal membranes is sphingomyelin (SM). Introduction of 70% SM to the DPPC monolayer decreased the Deltapi(max) from 4.7 to 1.1 mN/m, revealing the rigidifying effect of SM which was directly proportional to the amount of SM added. Modulation of fluidity of the membranes can alter the penetration of paclitaxel in biological membranes and hence its toxicity profile.

Correlating nanoscale titania structure with toxicity: a cytotoxicity and inflammatory response study with human dermal fibroblasts and human lung epithelial cells.

Nanocrystalline titanium dioxide (nano-TiO(2)) is an important material used in commerce today. When designed appropriately it can generate reactive species (RS) quite efficiently, particularly under ultraviolet (UV) illumination; this feature is exploited in applications ranging from self-cleaning glass to low-cost solar cells. In this study, we characterize the toxicity of this important class of nanomaterials under ambient (e.g., no significant light illumination) conditions in cell culture. Only at relatively high concentrations (100 microg/ml) of nanoscale titania did we observe cytotoxicity and inflammation; these cellular responses exhibited classic dose-response behavior, and the effects increased with time of exposure. The extent to which nanoscale titania affected cellular behavior was not dependent on sample surface area in this study; smaller nanoparticlulate materials had effects comparable to larger nanoparticle materials. What did correlate strongly to cytotoxicity, however, was the phase composition of the nanoscale titania. Anatase TiO(2), for example, was 100 times more toxic than an equivalent sample of rutile TiO(2). The most cytotoxic nanoparticle samples were also the most effective at generating reactive oxygen species; ex vivo RS species generation under UV illumination correlated well with the observed biological response. These data suggest that nano-TiO(2) samples optimized for RS production in photocatalysis are also more likely to generate damaging RS species in cell culture. The result highlights the important role that ex vivo measures of RS production can play in developing screens for cytotoxicity.

Interfacial properties as biophysical markers of cervical cancer.

Monolayers at air-liquid interfaces offer a convenient model for understanding the behavior of many natural systems like biological membranes. Langmuir monolayers were used to characterize the interfacial properties of tissue homogenates, organic phases and aqueous phases of tissue biopsy samples from 30 patients of cervical cancer and 15 normals. Our results reveal that the tensiometric parameters can differentiate between cancer and normal tissues obtained from human cervix and were statistically significant using t-test (P<0.05). The minimum surface tension of the cancer tissue monolayer was 52.9+/-4.4 mN/m, 1.4-folds greater than the normal cervical tissue homogenate value of 38.5+/-2.6 mN/m. The normal tissue homogenate isotherm had a hysteresis area of 90.3 microJ, which was approximately 6.2 times greater than that of the cervical cancer tissue monolayer. The total lipid and phospholipid contents of the cancerous cervical tissue were roughly double that of the normal cervical tissue and the surface activity was also in line with this observation. The difference in hysteresis of the cancerous and normal tissues indicates a decreased stability of the cancerous tissue film as compared to normal. The difference in surface activity denotes alterations in the molecular packing of the tissues in the cancerous state, which may have implications in terms of drug permeability and responsiveness. Further, differences in surface activity may play a role in altered cell adhesion and metastasis. This study is the first to evaluate surface properties of cancerous tissues and can lead to the development of a biophysical marker of cervical cancer based on interfacial properties.

Surface activity, lipid profiles and their implications in cervical cancer.

BACKGROUND: The profiles of lipids in normal and cancerous tissues may differ revealing information about cancer development and progression. Lipids being surface active, changes in lipid profiles can manifest as altered surface activity profiles. Langmuir monolayers offer a convenient model for evaluating surface activity of biological membranes. AIMS: The aims of this study were to quantify phospholipids and their effects on surface activity of normal and cancerous human cervical tissues as well as to evaluate the role of phosphatidylcholine (PC) and sphingomyelin (SM) in cervical cancer using Langmuir monolayers. METHODS AND MATERIALS: Lipid quantification was done using thin layer chromatography and phosphorus assay. Surface activity was evaluated using Langmuir monolayers. Monolayers were formed on the surface of deionized water by spreading tissue organic phase corresponding to 1 mg of tissue and studying their surface pressure-area isotherms at body temperature. The PC and SM contents of cancerous human cervical tissues were higher than those of the normal human cervical tissues. Role of PC and SM were evaluated by adding varying amounts of these lipids to normal cervical pooled organic phase. STATISTICAL ANALYSIS: Student's t-test (p < 0.05) and one-way analysis of variance (ANOVA) was used. RESULTS: Our results reveals that the phosphatidylglycerol level in cancerous cervical tissue was nearly five folds higher than that in normal cervical tissue. Also PC and sphingomyelin SM were found to be the major phospholipid components in cancerous and normal cervical tissues respectively. The addition of either 1.5 microg DPPC or 0.5 microg SM /mg of tissue to the normal organic phase changed its surface activity profile to that of the cancerous tissues. Statistically significant surface activity parameters showed that PC and SM have remarkable roles in shifting the normal cervical lipophilic surface activity towards that of cancerous lipophilic component. CONCLUSION: The Langmuir monolayer technique was sensitive to detect changes in tensiometric profiles of cervical cancers and these could be modulated by alterations in phosphatidylcholine and sphingomyelin levels. Therapeutic strategies may be designed to modulate these tensiometric profiles and lipid constituents of cancerous tissues.

Dynamic surface tensiometry of tissues using Langmuir films.

Langmuir monolayers are useful models of biomembranes as they allow simulation of biological conditions and rigorous thermodynamic analysis. This technique was used to characterize tissues at body temperature for the first time in our study. The organs studied include liver, kidney, stomach, testis, heart and brain from goat and certain human cancerous as well as their corresponding normal biopsies to reveal the potential of the tissue monolayer technique. Monolayers were formed on the surface of deionized water by spreading monolayer amounts of the tissue homogenates. The parameters calculated were minimum surface tension, relative lift off area, relative limiting area, compressibility and hysteresis area. Our results reveal that the parameters can differentiate between tissues obtained from different organs and were statistically significant using one-way ANOVA and Newman Keul's test (P<0.05). For example goat's stomach tissue had the lowest hysteresis area (DeltaG) value (27.6 microJ) whereas brain DeltaG value was nine folds higher than stomach value. Brain had the lowest minimum surface tension of 30.3+/-1.0 mN/m whereas stomach had a value of 40.5+/-0. 2 mN/m. Interestingly, the DeltaG values of human normal neck and esophageal tissues were 3.4 and 3.2 folds greater than that of their respective cancer tissues whereas the DeltaG values of vulval and breast cancer tissues were 4.6 and 4 folds greater than that of their respective normal tissues. While the gammamin values of neck cancer tissue showed 95% increase from normal tissue values, those of vulval and breast cancer tissues were 46 and 50% less compared to their respective normal tissue values. Though all the surface tensiometric parameters showed significant changes, minimum surface tension and hysteresis area were the most sensitive indicators of tissue types and diseased states. Further, the effects of therapeutics could also be monitored by this technique. This is evidenced by the post-radiotherapy tissue isotherms of neck and vulval cancers, where clinical radio-sensitivity was associated with a shift in the tensiometry towards their respective normal isotherms. The small sample amounts required, precision of the technique, very low within group variability, organ specificity and sensitivity to detect changes in diseased states make it a promising tool for prognostic evaluation of diseased states and monitoring effects of therapeutics. Further research is warranted in this promising and hitherto unexplored field of tissue tensiometry.