The effect of a single early high-dose vitamin D supplement on fracture union in patients with hypovitaminosis D: a prospective randomised trial.

AIMS: To evaluate the effect of a single early high-dose vitamin D supplement on fracture union in patients with hypovitaminosis D and a long bone fracture. PATIENTS AND METHODS: Between July 2011 and August 2013, 113 adults with a long bone fracture were enrolled in a prospective randomised double-blind placebo-controlled trial. Their serum vitamin D levels were measured and a total of 100 patients were found to be vitamin D deficient (< 20 ng/ml) or insufficient (< 30 ng/mL). These were then randomised to receive a single dose of vitamin D3 orally (100 000 IU) within two weeks of injury (treatment group, n = 50) or a placebo (control group, n = 50). We recorded patient demographics, fracture location and treatment, vitamin D level, time to fracture union and complications, including vitamin D toxicity. Outcomes included union, nonunion or complication requiring an early, unplanned secondary procedure. Patients without an outcome at 15 months and no scheduled follow-up were considered lost to follow-up. The t-test and cross tabulations verified the adequacy of randomisation. An intention-to-treat analysis was carried out. RESULTS: In all, 100 (89%) patients had hypovitaminosis D. Both treatment and control groups had similar demographics and injury characteristics. The initial median vitamin D levels were 16 ng/mL (interquartile range 5 to 28) in both groups (p = 0.885). A total of 14 patients were lost to follow-up (seven from each group), two had fixation failure (one in each group) and one control group patient developed an infection. Overall, the nonunion rate was 4% (two per group). No patient showed signs of clinical toxicity from their supplement. CONCLUSIONS: Despite finding a high level of hypovitaminosis D, the rate of union was high and independent of supplementation with vitamin D3. Cite this article: Bone Joint J 2017;99-B:1520-5.

Elaboration of a clinical and paraclinical score to estimate the probability of herpes simplex virus encephalitis in patients with febrile, acute neurologic impairment.

Herpes simplex virus (HSV) encephalitis is associated with a high risk of mortality and sequelae, and early diagnosis and treatment in the emergency department are necessary. However, most patients present with non-specific febrile, acute neurologic impairment; this may lead clinicians to overlook the diagnosis of HSV encephalitis. We aimed to identify which data collected in the first hours in a medical setting were associated with the diagnosis of HSV encephalitis. We conducted a multicenter retrospective case-control study in four French public hospitals from 2007 to 2013. The cases were the adult patients who received a confirmed diagnosis of HSV encephalitis. The controls were all the patients who attended the emergency department of Grenoble hospital with a febrile acute neurologic impairment, without HSV detection by polymerase chain reaction (PCR) in the cerebrospinal fluid (CSF), in 2012 and 2013. A multivariable logistic model was elaborated to estimate factors significantly associated with HSV encephalitis. Finally, an HSV probability score was derived from the logistic model. We identified 36 cases and 103 controls. Factors independently associated with HSV encephalitis were the absence of past neurological history (odds ratio [OR] 6.25 [95 % confidence interval (CI): 2.22-16.7]), the occurrence of seizure (OR 8.09 [95 % CI: 2.73-23.94]), a systolic blood pressure ≥140 mmHg (OR 5.11 [95 % CI: 1.77-14.77]), and a C-reactive protein <10 mg/L (OR 9.27 [95 % CI: 2.98-28.88]). An HSV probability score was calculated summing the value attributed to each independent factor. HSV encephalitis diagnosis may benefit from the use of this score based upon some easily accessible data. However, diagnostic evocation and probabilistic treatment must remain the rule.

Oxidative stress and lung pathology following geogenic dust exposure.

This study was designed to evaluate markers of systemic oxidative stress and lung histopathology following subacute exposure to geogenic dust with varying heavy metal content collected from a natural setting prone to wind erosion and used heavily for off-road vehicle recreation. Adult female B6C3F1 mice were exposed to several concentrations of dust collected from seven different types of surfaces at the Nellis Dunes Recreation Area in Clark County, Nevada, designated here as CBN 1-7. Dust representing each of the seven surface types, with an average median diameter of 4.2 µm, was selected and administered via oropharyngeal aspiration to mice at concentrations from 0.01 to 100 mg of dust kg(-1) of body weight. Exposures were given four times spaced a week apart over a 28 day period to mimic a month of weekend exposures. Lung pathology was evaluated while plasma markers of oxidative stress included levels of reactive oxygen and nitrogen species, superoxide dismutase, total antioxidant capacity and total glutathione. Overall, results of these assays to evaluate markers of oxidative stress indicate that no single CBN surface type was able to consistently induce markers of systemic oxidative stress at a particular dose or in a dose-response manner. All surface types were able to induce some level of lung inflammation, typically at the highest exposure levels. These data suggest that dust from the Nellis Dunes Recreation Area may present a potential health risk, but additional studies are necessary to characterize the full extent of health risks to humans. Copyright © 2016 John Wiley & Sons, Ltd.

Evaluation of the efficacy and safety of high dose short duration enrofloxacin treatment regimen for uncomplicated urinary tract infections in dogs.

BACKGROUND: Uncomplicated urinary tract infections (UTI) in dogs usually are treated with antimicrobial drugs for 10-14 days. Shorter duration antimicrobial regimens have been evaluated in human patients. HYPOTHESIS: A high dose short duration (HDSD) enrofloxacin protocol administered to dogs with uncomplicated UTI will not be inferior to a 14-day treatment regimen with amoxicillin-clavulanic acid. ANIMALS: Client-owned adult, otherwise healthy dogs with aerobic bacterial urine culture yielding ≥ 10(3) CFU/mL of bacteria after cystocentesis. METHODS: Prospective, multicenter, controlled, randomized blinded clinical trial. Enrolled dogs were randomized to group 1 (enrofloxacin 18-20 mg/kg PO q24h for 3 days) or group 2 (amoxicillin-clavulanic acid 13.75-25 mg/kg PO q12h for 14 days). Urine cultures were obtained at days 0, 10, and 21. Microbiologic and clinical cure rates were evaluated 7 days after antimicrobial treatment was discontinued. Lower urinary tract signs and adverse events also were recorded. RESULTS: There were 35 dogs in group 1 and 33 in group 2. The microbiologic cure rate was 77.1 and 81.2% for groups 1 and 2, respectively. The clinical cure rate was 88.6 and 87.9% for groups 1 and 2, respectively. Cure rates between groups did not differ according to the selected margin of noninferiority. CONCLUSIONS AND CLINICAL IMPORTANCE: HDSD enrofloxacin treatment was not inferior to a conventional amoxicillin-clavulanic acid protocol for the treatment of uncomplicated bacterial UTI in dogs. Further research is warranted to determine if this protocol will positively impact owner compliance and decrease the emergence of antimicrobial resistance.

[Long-term results after acetabular fractures with respect to heterotopic ossifications]. / Langzeitergebnisse nach Azetabulumfrakturen unter Berücksichtigung von heterotopen Ossifikationen.

BACKGROUND: Arthrosis, necrosis of the femoral head and heterotopic ossification (HO) tend to decline the outcome of acetabular fractures despite of good fracture reduction. In this study functional outcome and degree of HO were analyzed due to fracture type and surgical approach. The aim of this study is to delineate wether minimization of soft tissue damage increases the functional outcome. PATIENTS AND METHODS: 55 patients with surgically treated acetabular fractures (mean age: 40.4 (20-81) years, male 43, female 12) where retrospectively evaluated with a mean follow-up of 7.7 (4.4-12.3) years. Fractures were classified according to the Orthopaedic Trauma Association (OTA), functional outcome was scored by D'Aubigné-Postel and the degree of HO was defined by Brooker's classification. RESULTS: Following the OTA the distribution of fractures was: A-24 (44 %), B-23 (42 %) and C-8 (15 %). Mean D'Aubigné Index (max. 18 points) was 15.2, distributed to fracture type: A-15.9, B-15.0 and C-13.6. 32 % of all heterotopic ossifications were classified as Brooker 0, 10 % as Brooker 1, 29 % as Brooker 2 and Brooker 3 each, whereas Brooker 4 ossifications were not observed. 2/3 of the severe ossifications were observed using extended approaches or in case of type C fractures. The iliofemoral approach showed the tendency of fewer ossifications compared to extended approaches. CONCLUSION: Decrease of soft tissue damage during acetabular surgery plays an important role to improve outcome. Due to the higher risk of wrong implant position and insufficient reduction using a soft tissue sparing approach, we recommend a CT scan postoperatively to evaluate reduction and osteosynthesis.

Prevention of coordinated eye movements and steering impairs driving performance.

When approaching a bend in the road, a driver looks across to the inside kerb before turning the steering wheel. Eye movements and steering are tightly linked, with the eyes leading, which means that the oculomotor controller can assist the neural centres controlling steering. This optimum coordination is observed for all drivers; but despite being the preferred solution to the motor-control problem of successfully steering along a winding road, the question remains as to how crucial such coordinated eye and steering movements are for driving performance. Twenty subjects repeatedly drove a simulated stage of the World Rally Championship, aiming to complete the course in the fastest possible time. For the first six repetitions they used the usual coordination of eye movements and steering; for drives 7--12 they were instructed to fixate on a small spot in the centre of the screen (centre gaze). Prevention of coordination in this way impaired their performance (drives 6 and 7 compared), dramatically increasing their time taken to complete the course, equivalent to slipping 19 places down the leader board in the actual rally stage. This indicates that the usual pattern of eye movements correlated with steering is crucial for driving performance. Further experiments are suggested to reveal whether any attentional demand associated with keeping the eyes still contributes to the loss in performance.

[Postmortal diagnosis of Parkinson's disease]. / Zur postmortalen Diagnose des idiopathischen Morbus Parkinson.

Parkinson's disease is a continuously progressive degenerative disorder of the central, peripheral and enteric human nervous systems. Not only the substantia nigra, but also a number of other components of the motor and limbic systems, as well as the autonomic regulation, suffer heavy damages. Only a few of the many types of nerve cells in the human central nervous system develop the characteristic Lewy bodies and Lewy neurites. They are composed primarily of aggregated alpha-synuclein and lead to the premature destruction of the affected neurons. Due to the selective neuronal vulnerability, a distinctive distribution of changes occurs within the central nervous system, leading to a corresponding loss of functionality in many systems. The changes occur in an ordered timely fashion. The ascending pathological process begins within the brain at the glossopharyngeal and vagal areas, nearly destroys the substantia nigra, and reaches the mesocortex of the gray matter. From here it expands to further areas of the neocortex, thereby marking the end phase of the disease.

Immunological and hematological effects observed in B6C3F1 mice exposed to JP-8 jet fuel for 14 days.

JP-8 is the primary jet fuel used by the U.S. Air Force and NATO allies. Exposure is likely to be widespread and to include both military and aviation industry personnel as well as residents living near fuel contaminated sites. This study examines the effects of JP-8 on humoral and cell-mediated and hematological parameters. A suite of immunotoxicological endpoints was evaluated in adult female B6C3F1 mice gavaged with JP-8 (in an olive oil carrier) ranging from 250-2500 mg/kg/d for 14 d. One day following the last exposure, significant increases in liver mass were detected beginning at exposure levels of 1000 mg/kg/d, while thymic mass was decreased at exposure levels of 1500 mg/kg/d and above. Decreases in thymic cellularity, however, were only observed at exposure levels of 2000 mg/kg/d and above. Mean corpuscular volume was increased (1500-2500 mg/kg/d), while the hematocrit, hemoglobin concentration, and red blood cell count were decreased only at the 2500 mg/kg/d exposure level. Natural killer cell (NK) activity and T- and B-cell proliferation were not altered. Decreases in the plaque-forming cell (PFC) response were dose responsive at levels of 500 mg/kg/d and greater, while unexpectedly, serum levels of anti-SRBC immunoglobulin M (IgM) were not altered. Alterations were detected in thymic and splenic CD4/8 subpopulations, and proliferative responses of bone marrow progenitor cells were enhanced in mice exposed to 2000 mg/kg/d of JP-8. This study establishes that humoral immune function is impaired with lower exposure levels of JP-8 than are required to affect primary and secondary immune organ weights and cellularities, CD4/8 subpopulations, and hematological endpoints.

Pyridostigmine bromide (PYR) alters immune function in B6C3F1 mice.

Pyridostigmine bromide (PYR) is an anticholinesterase drug indicated for the treatment of myasthenia gravis and neuromuscular blockade reversal. It acts as a reversible cholinesterase inhibitor and was used as a pretreatment for soldiers during Operation Desert Storm to protect against possible nerve gas attacks. Since that time, PYR has been implicated as a possible causative agent contributing to Gulf War Illness. PYR's mechanism of action has been well-delineated with regards to its effects on the nervous system, yet little is known regarding potential effects on immunological function. To evaluate the effects of PYR on immunological function, adult female B6C3F1 mice were gavaged daily for 14 days with PYR (0, 1, 5, 10, or 20 mg/kg/day). Immune parameters assessed were lymphoproliferation, natural killer cell activity, the SRBC-specific antibody plaque-forming cell (PFC) response, thymus and spleen weight and cellularity, and thymic and splenic CD4/CD8 lymphocyte subpopulations. Exposure to PYR did not alter splenic and thymus weight or splenic cellularity. However, 20 mg PYR/kg/day decreased thymic cellularity with decreases in both CD4+/CD8+ (20 mg/kg/day) and CD4-/CD8- (10 and 20 mg/kg/day) cell types. Functional immune assays indicated that lymphocyte proliferative responses and natural killer cell activity were normal; whereas exposure to PYR significantly decreased primary IgM antibody responses to a T-cell dependent antigen at the 1, 5, 10 and 20 mg/kg treatment levels for 14 days. This is the first study to examine the immunotoxicological effects of PYR and demonstrate that this compound selectively suppresses humoral antibody responses.

Extract of the seed coat of Tamarindus indica inhibits nitric oxide production by murine macrophages in vitro and in vivo.

The seed coat extract of Tamarindus indica, a polyphenolic flavonoid, has been shown to have antioxidant properties. The present studies investigated the inhibitory effect of the seed coat extract of T. indica on nitric oxide production in vitro using a murine macrophage-like cell line, RAW 264.7, and in vitro and in vivo using freshly isolated B6C3F1 mouse peritoneal macrophages. In vitro exposure of RAW 264.7 cells or peritoneal macrophages to 0.2-200 microg/mL of T. indica extract significantly attenuated (as much as 68%) nitric oxide production induced by lipopolysaccharide (LPS) and interferon gamma (IFN-gamma) in a concentration-dependent manner. In vivo administration of T. indica extract (100-500 mg/kg) to B6C3F1 mice dose-dependently suppressed TPA, LPS and/or IFN-gamma induced production of nitric oxide in isolated mouse peritoneal macrophages in the absence of any effect on body weight. Exposure to T. indica extract had no effect on cell viability as assessed by the MTT assay. In B6C3F1 mice, preliminary safety studies demonstrated a decrease in body weight at only the highest dose tested (1000 mg/kg) without alterations in hematology, serum chemistry or selected organ weights or effects on NK cell activity. A significant decrease in body weight was observed in BALB/c mice exposed to concentrations of extract of 250 mg/kg or higher. Oral exposure of BALB/c mice to T. indica extract did not modulate the development of T cell-mediated sensitization to DNFB or HCA as measured by the local lymph node assay, or dermal irritation to nonanoic acid or DNFB. These studies suggest that in mice, T. indica extract at concentrations up to 500 mg/kg may modulate nitric oxide production in the absence of overt acute toxicity.

Subchronic exposure to ellagic acid impairs cytotoxic T-cell function and suppresses humoral immunity in mice.

Ellagic acid (EA) is present in a variety of foods such as grapes, strawberries, raspberries, and nuts. It is a dietary plant phenol that has been shown to inhibit oxidative stress and chemical carcinogenesis. Although several studies have examined the protective mechanisms of dietary EA including the induction of detoxifying enzymes, regulation of cell cycle, chelation of nickel, and prevention of DNA methylation, none have addressed the role of EA in immunological surveillance. This study investigates the status of immune function in B6C3F1 mice exposed continuously to EA in drinking water at 0.5, 1.0, or 2.0 mg/kg/day for 28 days. Although this range of exposure is above the estimated human daily intake (approximately 940 microg/day for 70 kg person or 13.4 microg/kg/day), these levels would not be unreasonable if EA were used as a dietary supplement or as a chemotherapeutic agent. Previous reports have demonstrated the anticarcinogenic effects of EA at levels 10- to 250-fold greater than those applied in this study. Immunological parameters assessed included natural killer (NK) cell activity, cytotoxic T lymphocyte (CTL) activity, IgM antibody plaque forming cell (PFC) response, thymus, spleen, kidney, and liver mass, and total cellularity for the thymus and spleen. Subchronic exposure to EA for 28 days in drinking water caused significant suppression of specific IgM antibody responses in the 2.0 mg/kg EA treatment group and suppressed cytotoxic T-cell function in the 0.5 and 1.0 mg/kg EA treatment groups. All other immunological parameters were within normal ranges. Kidney and liver mass were not altered after treatment with EA. The results from this study indicate that EA suppressed both IgM antibody responses and CTLs. These observations suggest important implications on human health should EA be prescribed as a chemotherapeutic agent or a preventative dietary supplement for cancer.

Interstitial cells subjacent to the entorhinal region expressing somatostatin-28 immunoreactivity are susceptible to development of Alzheimer's disease-related cytoskeletal changes.

Interstitial cells are isolated neurons located in the infracortical white matter that are known to express neuropeptides. Twenty-four cases selected for the absence, slight (Braak stages I-II), moderate (Braak stages III-IV), or serious degree (Braak stages V-VI) of cortical neurofibrillary pathology were studied for the presence of Alzheimer's disease-related abnormal tau in interstitial cells of the entorhinal region. AT8-immunoreactive white matter neurons were observed in all Braak stages of cortical neurofibrillary pathology. Both normal-appearing neurons and neurons with degenerative changes in the cellular processes were observed. Normal-appearing cells were predominantly found in stages I and II, whereas degenerative interstitial cells numerically increased from stage I onwards. The normal-appearing cells were medium-sized (10-25 micro m), with ovoid, fusiform, triangular or multipolar cell bodies, and showed an extensive dendritic field, which was oriented perpendicular to the direction of the perforant pathway. Since the morphology of the AT8-immunopositive normal-appearing cells was similar to that reported on somatostatinergic interstitial cells subjacent to the entorhinal region, double-labeling with AT8 and anti-somatostatin-28 (S309) was performed. All AT8-immunoreactive normal-appearing interstitial cells revealed co-staining with somatostatin-28 antiserum, whereas some of the AT8-immunopositive cells with degenerative processes reacted positively and others negatively with S309. In summary, a distinctive interstitial cell type characterized by extensive arborization oriented perpendicular to the course of the perforant pathway and showing somatostatin expression is susceptible to developing the Alzheimer's disease-related cytoskeletal changes. Progression in cytoskeleton change is accompanied by loss of somatostatin.

Quantifying the relationship between multiple immunological parameters and host resistance: probing the limits of reductionism.

Although reductionist experimental designs are excellent for identifying cells, molecules, or functions involved in resistance to particular microbes or cancer cells, they do not provide an integrated, quantitative view of immune function. In the present study, mice were treated with either dexamethasone (DEX) or cyclosporin A (CyA), and immune function and host resistance were evaluated. Multivariate statistical methods were used to describe the relative importance of a broad range of immunological parameters for host resistance in mice treated with various dosages of DEX. Multiple regression and logistic regression analysis indicated that changes in 24 immunological parameters explained a substantial portion of the changes in resistance to B16F10 tumor cells or streptococcus group B. However, at least 40% of the change in host resistance remained unexplained. DEX at all dosages substantially suppressed numerous relevant immunological parameters, but significantly decreased resistance to Listeria monocytogenes only at the highest dosage. In contrast, CyA substantially decreased resistance to L. monocytogenes at dosages that caused relatively minor suppression of just a few immunological parameters (unfortunately, CyA data and host resistance data for L. monocytogenes were not suitable for multivariate analysis). These results illustrate that mathematical models can be used to explain changes in host resistance on the basis of changes in immune parameters, and that moderate changes in relevant immunological parameters may not produce the types of changes in host resistance expected on the basis of results from reductionist experimental designs.

Toxicology of metam sodium.

Metam sodium is the third most commonly used agricultural pesticide (by weight) in the U.S. A spill of 19,000 gallons of metam sodium into the Sacramento River in 1991 clearly demonstrated that a major uncontrolled release can have adverse ecological and human health effects. Furthermore, this incident revealed that estimates of Reference Exposure Levels for the major breakdown product of metam sodium (methylisothiocyanate, MITC) were reasonable with regard to the induction of discomfort. In fact, the irritant properties of MITC seem to account for many of the most commonly reported symptoms in this incident. However, neurotoxicity may also account for some of these symptoms. There is evidence that metam sodium can act as a contact sensitizer in humans, inducing allergic dermatitis. It also may exacerbate or induce respiratory allergy (asthma). The ecological impact of routine use of metam sodium is not clear, but adverse effects on non-target plants have been inferred from modeling studies, and adverse effects on soil microbes have been observed. These issues deserve further study. Human health effects of occupational or routine environmental exposure to metam sodium are not known, but there is limited evidence for immunological (hypersensitivity) and developmental effects as well as irritation and associated symptoms. Animal studies suggest a potential for immunological, developmental, carcinogenic, and atherogenic effects. Metam sodium and some of its breakdown products have a wide variety of molecular and cellular actions that could explain the health effects noted here. However, further studies are needed to relate specific molecular or cellular actions to specific health effects.

alpha-synuclein immunopositive Parkinson's disease-related inclusion bodies in lower brain stem nuclei.

Advanced silver stains and immunohistochemical reactions against alpha-synuclein were used to detect Parkinson's disease-related cytoskeletal abnormalities in select lower brain stem nuclei. Various types of inclusion bodies including inconspicuous and heretofore unnoted granular particles and thread-like Lewy neurites were visualized. Of the nuclei investigated (gigantocellular reticular nucleus, bulbar raphe nuclei, coeruleus-subcoeruleus area), only lipofuscin- or neuromelanin-laden neuronal types showed a propensity to develop the pathological changes. Neuronal types devoid of pigment deposits remained free of the cytoskeletal abnormalities. Fine, dust-like particles and small globular Lewy bodies were encountered solely within the limits of intraneuronal lipofuscin or neuromelanin deposits.

An aryl hydrocarbon receptor independent mechanism of JP-8 jet fuel immunotoxicity in Ah-responsive and Ah-nonresponsive mice.

JP-8 jet fuel is handled extensively by personnel in the military and commercial airlines, despite the paucity of information regarding its potential human health effects. JP-8 is a complex mixture primarily consisting of kerosene plus aliphatic and aromatic hydrocarbons. Recent reports indicate that acute JP-8 exposure via inhalation or dermal routes can overtly and persistently impair immune function in mice. Data from preliminary studies in this laboratory assessing the immunotoxicity of JP-8 indicated that oral JP-8 exposure caused an increase in liver weight, a decrease in thymus weight, and a decrease in the PFC response. As these results were similar to classic effects elicited by TCDD, a strong AhR ligand, it was hypothesized that JP-8 may exert immunosuppression via a similar mechanism. To test this hypothesis, an Ah-responsive mouse strain (B6C3F1) and a classically non-responsive mouse strain (DBA/2) bearing a lower affinity AhR were gavaged with JP-8 for 7 days. The results suggest that both mouse strains were equally sensitive to JP-8's toxicity at several endpoints including thymus weight and cellularity, liver weight, and specific IgM antibody responses. Furthermore, JP-8 did not induce CYP1A1 or promote down regulation of the AhR when evaluated by Western blot in either B6C3F1 or DBA/2 mice. In vitro studies corroborated these findings as JP-8 did not induce CYP1A1, promote down regulation of the AhR, or activate an XRE-driven reporter gene in murine Hepa-1 cells. These results suggest that JP-8 may exert its toxicity via an AhR-independent mechanism.

Polymer gels for magnetic resonance imaging of radiation dose distributions at normal room atmosphere.

Polymer gels whose NMR and optical properties change when irradiated offer unique advantages for measuring radiation dose distributions. To date, all acrylic polymer gel dosimeters must be manufactured, stored and irradiated in hypoxic conditions which severely limits their use and stability. A new formulation of acrylic dosimeter gel has been developed that responds well in normal atmosphere and which we have named MAGIC (Methacrylic and Ascorbic acid in Gelatin Initiated by Copper). To produce dosimeter gels, an aqueous solution of gelatin, open to the atmosphere, is mixed with methacrylic acid, copper(II) ions, ascorbic acid and hydroquinone. It is believed that the copper(II) and ascorbic acid form a complex with oxygen which (with radiolysis of water) serves as a free radical source for the initiation of the polymerization of methacrylic acid. At room air the water proton spin relaxation rate R2 in MAGIC gels is proportional to absorbed dose though the precise relationship depends on the composition of the gel and the initiating complex. For example, in the range 0-30 Gy the slope of the response of R2 versus dose at 20 MHz was 0.300, 0.519 and 0.681 s(-1) Gy(-1), respectively, when the concentration of MAA was 3, 6 and 9%. The slopes increased to 0.310, 0.567 and 0.868 s(-1) Gy(-1) at 85 MHz. An important determinant of the sensitivity to detect small dose changes is shown to be the slope-to-intercept ratio of the dose-response curve. These varied from 0.08 to 0.17, comparable to hypoxic gels described earlier. MAGIC gels can be manufactured and used much more easily than the previous formulations and can be imaged by magnetic resonance imaging or optical scanning, and thus they will likely be of considerable interest to radiation physicists.

Evaluation of immunotoxicity induced by single or concurrent exposure to N,N-diethyl-m-toluamide (DEET), pyridostigmine bromide (PYR), and JP-8 jet fuel.

Approximately 5,000 to 80,000 of the US service personnel involved in the Persian Gulf War have complained of a variety of nonspecific symptoms since their return in 1991. These symptoms have been collectively labeled Gulf War Illness and include muscle fatigue, general malaise, myalgia, impaired cognition, ataxia, headaches, fever, joint pain, skin rash, gastrointestinal disturbances, sleep disturbances, and respiratory difficulties. Exposures of military and service personnel were diverse and included the prescribed anti-nerve gas agent pyridostigmine bromide (PYR), N.N-diethyl-m-toluamide (DEET) insect repellent, and environmental exposures to jet fuel. Thus, studies in our laboratory were undertaken to determine if concurrent exposure to these agents, singly or in combination, would contribute to significant alterations in immunological function and disease susceptibility. To assess immune status, eight-week old B6C3F1 female mice were exposed for 14 days to single compounds or tertiary mixtures of 15.5 mg/kg DEET, 2 mg/kg PYR, and 500 mg/kg JP-8 (termed low dose), or 31 mg/kg DEET, 5 mg/kg PYR, and 1,000 mg/kg JP-8 (termed high dose). Immunosuppression was assessed 24 h after the last exposure. No remarkable alterations were evident in hematological parameters, spleen and thymus organ weight and total cellularity, natural killer (NK) cell activity, cytotoxic T-cell activity, or mitogen-induced lymphocyte proliferation after exposure to either single or tertiary mixtures at low or high doses. A few changes in CD4/CD8 flow cytometric lymphocyte subpopulations were detected after exposure to the tertiary mixture at the high dose. Delayed type hypersensitivity (DTH) was decreased by 88% after exposure to the high-dose mixture, and suppression of antibody-specific IgM immune responses (plaque-forming cell, PFC) occurred after exposure to all single and tertiary mixtures at both dose levels. In the PFC response, antagonism was apparent in the mixture, while coexposure to these agents resulted in a synergistic effect in the DTH response. Susceptibility to B16F10 tumor or Listeria monocytogenes challenge was not affected after single or tertiary exposures. These data suggest that combined exposure to DEET, PYR, and JP-8 does not profoundly alter many immunological endpoints, but does selectively target functional endpoints such as the PFC and DTH response. This should be considered when assessing human health risks in the military environment.

Theory and practice in sport psychology and motor behaviour needs to be constrained by integrative modelling of brain and behaviour.

Because of advances in technology, the non-invasive study of the human brain has enhanced the knowledge base within the neurosciences, resulting in an increased impact on the psychological study of human behaviour. We argue that application of this knowledge base should be considered in theoretical modelling within sport psychology and motor behaviour alongside existing ideas. We propose that interventions founded on current theoretical and empirical understanding in both psychology and the neurosciences may ultimately lead to greater benefits for athletes during practice and performance. As vehicles for exploring the arguments of a greater integration of psychology and neurosciences research, imagery and perception-action within the sport psychology and motor behaviour domains will serve as exemplars. Current neuroscience evidence will be discussed in relation to theoretical developments; the implications for sport scientists will be considered.