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A cluster-randomized trial evaluating the effectiveness of chlorhexidine gluconate-impregnated wipes against skin and soft tissue infections (SSTIs) and colonization with methicillin-resistant Staphylococcus aureus (MRSA) was conducted among military recruits attending Officer Candidate School at Marine Corps Base Quantico, Virginia. Participants were instructed to use the wipes thrice weekly and were monitored daily for SSTI. Surveys assessed frequency of wipe use as well as knowledge and attitudes regarding MRSA SSTI. Use of chlorhexidine gluconate-impregnated wipes failed to prevent SSTI; however, study adherence was moderate. Adherence with the study regimen (defined as use of > or = 50% of the wipes) was 65% at week 2 and declined to 49% by week 6. Adherence was approximately 59% in the first two classes and declined in later classes. One-third felt that use of the wipes was disruptive. Participants were knowledgeable about MRSA SSTI prevention measures. However, only 53% agreed that MRSA commonly causes skin infections in military training facilities. Understanding adherence and its determinants is needed to optimize prevention strategies that require self-administration. Future efforts should address barriers to adherence with prevention strategies in recruit training settings.

Background: Evidence of serotonergic involvement in vestibular pathway contributions to migraine and balance disorders is compelling. Serotonergic 5-HT1B and 5-HT1D receptors are expressed extensively in inner ear ganglia of monkeys and rats. The serotonergic 5-HT1F receptor is also a target of triptans. This study describes its distribution in vestibular and trigeminal ganglia of monkeys. Methods: Using primary polyclonal antibodies raised against oligopeptides specific for the human 5-HT1F receptor, neuronal somatic area and intensity of immunoreactive vestibular and trigeminal ganglia were quantified. Results and Discussion: Virtually all vestibular and considerable trigeminal ganglia showed positive 5-HT1F receptor immunoreactivity. Inferior and superior vestibular ganglia staining appeared confined to distinct cell regions, varying considerably among cells of different sizes: more intense in small, punctate in some medium and regionally polarized in some large cells. Analyses of average somatic vestibular neuronal immunoreactive intensity identified mainly medium sized cells with high standard deviation of intensity corresponding to punctately-stained cells. Less variability occurred in somatic intensity staining and cellular distribution among 5-HT1F receptor immunopositive trigeminal ganglia. Most exhibited similar punctate staining patterns, higher mean somatic immunoreactive intensity and larger neuronal somatic size proportions per size distribution subpopulation compared to vestibular ganglia size distribution populations. Centrally directed vestibular ganglion neuronal processes, cochlear inner hair cells, vestibular hair cells and blood vessels in vestibular maculae and cristae were immunoreactive. The 5-HT1F receptor expression in vestibular ganglia shows complex variable staining intensity patterns associated with cell size of immunopositive neurons, not seen in immunopositive trigeminal ganglia and not previously evident with 5-HT1B and 5-HT1D receptor subtype immunoreactivity in vestibular ganglia. These data motivate exploration of 5-HT1 receptor oligomerization and ligand functional selectivity in differential serotonergic involvement in co-morbidity of migraine and balance disorders. Similar findings in cochlear inner hair cell afferents are applicable to migraine related tinnitus or hypercusis (phonophobia).

While it is evident that nasal colonization with S. aureus increases the likelihood of SSTI, there is a significant lack of information regarding the contribution of extranasal colonization to the overall risk of a subsequent SSTI. Furthermore, the impact of S. aureus colonization on bacterial community composition outside the nasal microbiota is unclear. Thus, this report represents the first investigation that utilized both culture and high-throughput sequencing techniques to analyze microbial dysbiosis at multiple body sites of healthy and diseased/colonized individuals. The results described here may be useful in the design of future methodologies to treat and prevent SSTIs., Skin and soft tissue infections (SSTIs) are common in the general population, with increased prevalence among military trainees. Previous research has revealed numerous nasal microbial signatures that correlate with SSTI development and Staphylococcus aureus colonization. Thus, we hypothesized that the ecology of the inguinal, oropharynx, and perianal regions may also be altered in response to SSTI and/or S. aureus colonization. We collected body site samples from 46 military trainees with purulent abscess (SSTI group) as well as from 66 asymptomatic controls (non-SSTI group). We also collected abscess cavity samples to assess the microbial composition of these infections. Samples were analyzed by culture, and the microbial communities were characterized by high-throughput sequencing. We found that the nasal, inguinal, and perianal regions were similar in microbial composition and significantly differed from the oropharynx. We also observed differences in Anaerococcus and Streptococcus abundance between the SSTI and non-SSTI groups for the nasal and oropharyngeal regions, respectively. Furthermore, we detected community membership differences between the SSTI and non-SSTI groups for the nasal and inguinal sites. Compared to that of the other regions, the microbial compositions of the nares of S. aureus carriers and noncarriers were dramatically different; we noted an inverse correlation between the presence of Corynebacterium and the presence of Staphylococcus in the nares. This correlation was also observed for the inguinal region. Culture analysis revealed elevated methicillin-resistant S. aureus (MRSA) colonization levels for the SSTI group in the nasal and inguinal body sites. Together, these data suggest significant microbial variability in patients with SSTI as well as between S. aureus carriers and noncarriers. IMPORTANCE While it is evident that nasal colonization with S. aureus increases the likelihood of SSTI, there is a significant lack of information regarding the contribution of extranasal colonization to the overall risk of a subsequent SSTI. Furthermore, the impact of S. aureus colonization on bacterial community composition outside the nasal microbiota is unclear. Thus, this report represents the first investigation that utilized both culture and high-throughput sequencing techniques to analyze microbial dysbiosis at multiple body sites of healthy and diseased/colonized individuals. The results described here may be useful in the design of future methodologies to treat and prevent SSTIs.

Bacteria often live in biofilms, which are microbial communities surrounded by a secreted extracellular matrix. Here, we demonstrate that hydrodynamic flow and matrix organization interact to shape competitive dynamics in Pseudomonas aeruginosa biofilms. Irrespective of initial frequency, in competition with matrix mutants, wild-type cells always increase in relative abundance in planar microfluidic devices under simple flow regimes. By contrast, in microenvironments with complex, irregular flow profiles – which are common in natural environments – wild-type matrix-producing and isogenic non-producing strains can coexist. This result stems from local obstruction of flow by wild-type matrix producers, which generates regions of near-zero shear that allow matrix mutants to locally accumulate. Our findings connect the evolutionary stability of matrix production with the hydrodynamics and spatial structure of the surrounding environment, providing a potential explanation for the variation in biofilm matrix secretion observed among bacteria in natural environments. DOI: http://dx.doi.org/10.7554/eLife.21855.001, eLife digest Bacteria often live together – attached to surfaces like river rocks, water pipes, the lining of the gut and catheters – in communities called biofilms. These groups of bacteria are small-scale ecosystems in which cells cooperate and compete with one another to obtain resources, such as food and space to grow. Within a biofilm, a sticky glue-like substance called the matrix binds the cells to each other and to the surface. Cells that make the matrix typically have an advantage over those that do not because they can better resist the shearing forces experienced when liquid flows over the surface. The matrix also helps cells to capture nutrients from the passing liquid. Nevertheless, not all strains of bacteria make matrix, despite its advantages. Because of where they can grow, biofilms are fundamentally important in the environment, in industry and in infections. Resolving why some bacteria make matrix while others do not could therefore allow scientists and engineers to re-design the surfaces involved in these settings to discourage harmful biofilms or to encourage beneficial ones. Nadell, Ricaurte et al. have now used a bacterium called Pseudomonas aeruginosa to explore how the properties of the surface and the flowing liquid affect matrix production among cells in biofilms. P. aeruginosa typically lives in soil and can cause infections in people, especially in hospital patients and people who have weakened immune systems. Nadell, Ricaurte et al. studied normal P. aeruginosa bacteria and a mutant strain that is unable to make matrix. The strains were labeled with fluorescent markers and put into special chambers that simulated different environments. The proportion of each strain was measured after three days of biofilm growth. When biofilms were grown under flowing liquid in simple environments with flat surfaces, matrix producers always outcompeted non-producers. However, the two strains coexisted in more complex and porous environments, like those found in soil. Nadell, Ricaurte et al. went on to show that the strains could co-exist because the matrix producers made biofilms that created areas within the environment where the liquid flows very slowly or not at all. In these regions, non-producing cells could compete successfully because resistance to shearing forces is less important when flow is weak or absent, and so the non-producing cells were not washed away. The results begin to explain why matrix production among cells in environmental settings is diverse and highlight that the environment is important in the evolution of bacterial biofilms. DOI: http://dx.doi.org/10.7554/eLife.21855.002

Bacteria often live in biofilms, which are microbial communities surrounded by a secreted extracellular matrix. Here, we demonstrate that hydrodynamic flow and matrix organization interact to shape competitive dynamics inPseudomonas aeruginosabiofilms. Irrespective of initial frequency, in competition with matrix mutants, wild type cells always increase in relative abundance in straight-tunnel microfluidic devices under simple flow regimes. By contrast, in microenvironments with complex, irregular flow profiles - which are common in natural environments - wild type matrix-producing and isogenic non-producing strains can coexist. This result stems from local obstruction of flow by wild-type matrix producers, which generates regions of near-zero flow speed that allow matrix mutants to locally accumulate. Our findings connect the evolutionary stability of matrix production with the hydrodynamics and spatial structure of the surrounding environment, providing a potential explanation for the variation in biofilm matrix secretion observed among bacteria in natural environments.Impact StatementThe feedback between hydrodynamic flow conditions and biofilm spatial architecture drives competition inP. aeruginosabiofilms, and can explain the variation in biofilm production observed among bacteria in natural environments.

On its own, a single cell cannot exert more than a microscopic influence on its immediate surroundings. However, via strength in numbers and the expression of cooperative phenotypes, such cells can enormously impact their environments. Simple cooperative phenotypes appear to abound in the microbial world, but explaining their evolution is challenging because they are often subject to exploitation by rapidly growing, non-cooperative cell lines. Population spatial structure may be critical for this problem because it influences the extent of interaction between cooperative and non-cooperative individuals. It is difficult for cooperative cells to succeed in competition if they become mixed with non-cooperative cells, which can exploit the public good without themselves paying a cost. However, if cooperative cells are segregated in space and preferentially interact with each other, they may prevail. Here we use a multi-agent computational model to study the origin of spatial structure within growing cell groups. Our simulations reveal that the spatial distribution of genetic lineages within these groups is linked to a small number of physical and biological parameters, including cell growth rate, nutrient availability, and nutrient diffusivity. Realistic changes in these parameters qualitatively alter the emergent structure of cell groups, and thereby determine whether cells with cooperative phenotypes can locally and globally outcompete exploitative cells. We argue that cooperative and exploitative cell lineages will spontaneously segregate in space under a wide range of conditions and, therefore, that cellular cooperation may evolve more readily than naively expected., Author Summary Cooperation is a fundamental and widespread phenomenon in nature, yet explaining the evolution of cooperation is difficult. Natural selection typically favors individuals that maximize their own reproduction, so how is it that many diverse organisms, from bacteria to humans, have evolved to help others at a cost to themselves? Research has shown that cooperation can most readily evolve when cooperative individuals preferentially help each other, but this leaves open another critical question: How do cooperators achieve selective interaction with one another? We focus on this question in the context of unicellular organisms, such as bacteria, which exhibit simple forms of cooperation that play roles in nutrient acquisition and pathogenesis. We use a realistic simulation framework to model large cell groups, and observe that cell lines can spontaneously segregate from each other in space as the group expands. Finally, we demonstrate that lineage segregation allows cooperative cell types to preferentially benefit each other, thereby favoring the evolution of cooperation.

This study provides the first clear evidence that the generation of optokinetic nystagmus fast phases (FPs) is a decision process that is influenced by performance of a concurrent disjunctive reaction time task (DRT). Ten subjects performed an auditory DRT during constant velocity optokinetic stimulation. Eye movements were measured in three dimensions with a magnetic search coil. Slow phase (SP) durations were defined as the interval between FPs. There were three main findings. Firstly, human optokinetic nystagmus SP durations are consistent with a model of a Gaussian basic interval generator (a type of biological clock), such that FPs can be triggered randomly at the end of a clock cycle (mean duration: 200–250 ms). Kolmogorov-Smirnov tests could not reject the modeled cumulative distribution for any data trials. Secondly, the FP need not be triggered at the end of a clock cycle, so that individual SP durations represent single or multiple clock cycles. Thirdly, the probability of generating a FP at the end of each interval generator cycle decreases significantly during performance of a DRT. These findings indicate that the alternation between SPs and FPs of optokinetic nystagmus is not purely reflexive. Rather, the triggering of the next FP is postponed more frequently if a recently presented DRT trial is pending action when the timing cycle expires. Hence, optokinetic nystagmus FPs show dual-task interference in a manner usually attributed to voluntary movements, including saccades. NEW & NOTEWORTHY This study provides the first clear evidence that the generation of optokinetic nystagmus (OKN) fast phases is a decision process that is influenced by performance of a concurrent disjunctive reaction time task (DRT). The slow phase (SP) durations are consistent with a Gaussian basic interval generator and multiple interval SP durations occur more frequently in the presence of the DRT. Hence, OKN shows dual-task interference in a manner observed in voluntary movements, such as saccades.

To date, the outcomes of cartilage repair have been inconsistent and have frequently yielded mechanically inferior fibrocartilage, thereby increasing the chances of damage recurrence. Implantation of constructs with biochemical composition and mechanical properties comparable to natural cartilage could be advantageous for long-term repair. This study attempted to create such constructs, in vitro, using tissue engineering principles. Bovine synoviocytes were seeded on nonwoven polyethylene terephthalate fiber scaffolds and cultured in chondrogenic medium for 4 weeks, after which uniaxial compressive loading was applied using an in-house bioreactor for 1 h per day, at a frequency of 1 Hz, for a further 84 days. The initial loading conditions, determined from the mechanical properties of the immature constructs after 4 weeks in chondrogenic culture, were strains ranging between 13% and 23%. After 56 days (sustained at 84 days) of loading, the constructs were stained homogenously with Alcian blue and for type-II collagen. Dynamic compressive moduli were comparable to the high end values for native cartilage and proportional to Alcian blue staining intensity. We suggest that these high moduli values were attributable to the bioreactor setup, which caused the loading regime to change as the constructs developed, that is, the applied stress and strain increased with construct thickness and stiffness, providing continued sufficient cell stimulation as further matrix was deposited. Constructs containing cartilage-like matrix with response to load similar to that of native cartilage could produce long-term effective cartilage repair when implanted.

Traumatic brain injury is an increasingly common public health issue, with the mild variant most clinically relevant for this chapter. Common causes of mild traumatic brain injury (mTBI) include motor vehicle accidents, athletics, and military training/deployment. Despite a range of clinically available testing platforms, diagnosis of mTBI remains challenging. Symptoms are primarily neurosensory, and include dizziness, hearing problems, headaches, cognitive, and sleep disturbances. Dizziness is nearly universally present in all mTBI patients, and is the easiest symptom to objectify for diagnosis. Aside from a thorough history and physical exam, in the near future specialized vestibular function tests will be key to mTBI diagnosis. A battery of oculomotor (antisaccade, predictive saccade) and vestibular tasks (head impulse test) has been demonstrated to sensitively and specifically identify individuals with acute mTBI. Vestibular therapy and rehabilitation have shown improvements for mTBI patients in cognitive function, ability to return to activities of daily living, and ability to return to work. Dizziness, as a contributor to short- and long-term disability following mTBI, is ultimately crucial not only for diagnosis but also for treatment.

Neuronal networks that are linked to the peripheral vestibular system contribute to gravitoinertial sensation, balance control, eye movement control, and autonomic function. Ascending connections to the limbic system and cerebral cortex are also important for motion perception and threat recognition, and play a role in comorbid balance and anxiety disorders. The vestibular system also shows remarkable plasticity, termed vestibular compensation. Activity in these networks is regulated by an interaction between: (1) intrinsic neurotransmitters of the inner ear, vestibular nerve, and vestibular nuclei; (2) neurotransmitters associated with thalamocortical and limbic pathways that receive projections originating in the vestibular nuclei; and (3) locus coeruleus and raphe (serotonergic and nonserotonergic) projections that influence the latter components. Because the ascending vestibular interoceptive and thalamocortical pathways include networks that influence a broad range of stress responses (endocrine and autonomic), memory consolidation, and cognitive functions, common transmitter substrates provide a basis for understanding features of acute and chronic vestibular disorders.

Military trainees are at high risk for skin and soft-tissue infections (SSTIs). Although Staphylococcus aureus is associated with purulent SSTI, it is unclear to what degree this pathogen causes nonpurulent cellulitis. To inform effective prevention strategies and to provide novel insights into SSTI pathogenesis, we aimed to determine the etiology of SSTI in this population. We conducted a prospective observational study in US Army Infantry trainees with SSTI (cutaneous abscesses and cellulitis) from July 2012 through December 2014. We used standard microbiology, serology, and high-throughput sequencing to determine the etiology of SSTI. Furthermore, we compared purported risk factors as well as anatomic site colonization for S. aureus. Among 201 SSTI cases evaluated for SSTI risk factors, cellulitis was associated with lower extremity blisters (P = 0.01) and abscess was associated with methicillin-resistant S. aureus (MRSA) colonization (P

We examined relationships between livestock grazing and the activity of introduced rodents and population density of Jewelled Geckos, Naultinus gemmeus (Diplodactylidae) on the Otago Peninsula, South Island, New Zealand. We expected livestock grazing to prevent the proliferation of rank grass (which is often associated with high rodent densities) and thereby reduce the frequency of predation by rodents on Jewelled Geckos. Thus, we predicted activity of rodents to be lower, and density of Jewelled Geckos higher, at sites grazed by livestock. We tested this for two habitats: Coprosma spp. shrubland and regenerating kānuka (Kunzea ericoides) forest. We quantified density of Jewelled Geckos using visual searches, photography and mark–recapture (POPAN formulation). We used tracking tunnel surveys to estimate the activity of introduced rodents. The activity of rodents (Rattus spp. and Mus musculus) was significantly higher at ungrazed compared to grazed sites in both habitats. Density of Jewelled Geckos in Coprosma was over four times higher at grazed sites and decreased with increasing rodent activity; however, in kānuka, we found a contrasting result with density being significantly higher at the ungrazed sites. We infer that in ungrazed Coprosma, rank grasses support high rodent densities and, consequently, high predation of Jewelled Geckos. Thus, grazing by introduced livestock may promote the survival of Jewelled Geckos and the persistence of high density populations in Coprosma shrubland. In contrast, grazing in regenerating kānuka may impact on Jewelled Geckos negatively, possibly by removing thermal refugia.

The 2011 Model of the Clinical Practice of Emergency Medicine. ACADEMIC EMERGENCY MEDICINE 2012; 19:000–000 © 2012 by the Society for Academic Emergency Medicine

Bacteria commonly grow in densely populated surface-bound communities, termed biofilms, where they gain benefits including superior access to nutrients and resistance to environmental insults. The secretion of extracellular polymeric substances (EPS), which bind bacterial collectives together, is ubiquitously associated with biofilm formation. It is generally assumed that EPS secretion is a cooperative phenotype that benefits all neighboring cells, but in fact little is known about the competitive and evolutionary dynamics of EPS production. By studying Vibrio cholerae biofilms in microfluidic devices, we show that EPS-producing cells selectively benefit their clonemates and gain a dramatic advantage in competition against an isogenic EPS-deficient strain. However, this advantage carries an ecological cost beyond the energetic requirement for EPS production: EPS-producing cells are impaired for dispersal to new locations. Our study establishes that a fundamental tradeoff between local competition and dispersal exists among bacteria. Furthermore, this tradeoff can be governed by a single phenotype.

Study objective We characterize and compare the work activities, including peak patient loads, associated with the workplace in the academic and community emergency department (ED) settings. This allows assessment of the effect of future ED system operational changes and identifies potential sources contributing to medical error. Methods This was an observational, time-motion study. Trained observers shadowed physicians, recording activities. Data included total interactions, distances walked, time sitting, patients concurrently treated, interruptions, break in tasks, physical contact with patients, hand washing, diagnostic tests ordered, and therapies rendered. Activities were classified as direct patient care, indirect patient care, or personal time with a priori definitions. Results There were 203 2-hour observation periods of 85 physicians at 2 academic EDs with 100,000 visits per year at each (N=160) and 2 community EDs with annual visits of 19,000 and 21,000 (N=43). Reported data present the median and minimum-maximum values per 2-hour period. Emergency physicians spent the majority of time on indirect care activities (academic 64 minutes, 29 to 91 minutes; community 55 min, 25 to 95 minutes), followed by direct care activities (academic 36 minutes, 6 to 79 minutes; community 41 minutes, 5 to 60 minutes). Personal time differed by location type (academic 6 minutes, 0 to 66 minutes; community 13 minutes, 0 to 69 minutes). All physicians simultaneously cared for multiple patients, with a median number of patients greater than 5 (academic 7 patients, 2 to 16 patients; community 6 patients, 2 to 12 patients). Conclusion Emergency physicians spend the majority of their time involved in indirect patient care activities. They are frequently interrupted and interact with a large number of individuals. They care for a wide range of patients simultaneously, with surges in multiple patient care responsibilities. Physicians working in academic settings are interrupted at twice the rate of their community counterparts.

The comorbidity among balance disorders, anxiety disorders and migraine has been studied extensively from clinical and basic research perspectives. From a neurological perspective, the comorbid symptoms are viewed as the product of sensorimotor, interoceptive and cognitive adaptations that are produced by afferent interoceptive information processing, a vestibulo–parabrachial nucleus network, a cerebral cortical network (including the insula, orbitofrontal cortex, prefrontal cortex and anterior cingulate cortex), a raphe nuclear–vestibular network, a coeruleo–vestibular network and a raphe–locus coeruleus loop. As these pathways overlap extensively with pathways implicated in the generation, perception and regulation of emotions and affective states, the comorbid disorders and effective treatment modalities can be viewed within the contexts of neurological and psychopharmacological sites of action of current therapies.

To better understand the epidemiology of diarrhea in deployed personnel to the Middle East, a prospective cohort study of travelers' diarrhea (TD) was conducted between May 2004 and January 2005 at the Multinational Force and Observers (MFO) camp in the southern Sinai. A baseline entry questionnaire and stool specimen was provided on study entry, and volunteers were followed every 6 weeks. Of 211 volunteers, 145 (68.7%) completed one or more follow-up visits. In total, 416 follow-up surveys were completed, which described an overall incidence of 25.2 episodes per 100 person months (95% confidence interval = 21.2-30.0). Additionally, stools were collected in 72 of 77 diarrhea-associated clinic visits, with bacterial pathogens most commonly isolated (enterotoxigenic Escherichia coli in 30 [42%] samples and Campylobacter jejuni in 7 [10%] samples) Despite modern preventive methods, diarrhea is still a common problem for deployed US military personnel in Egypt, frequently resulting in diminished ability to work.

The association between migraine and balance disorder morbidities has been a topic of interest for many years, and serotonin (5-HT) receptor is known to be closely related with migraine and also to be associated with vestibular symptoms. However, the mechanism underlying the pathogenesis of migrainous vertigo and its association with 5-HT has not been elucidated. Of the many 5-HT receptors, 5-HT 7 receptor has recently attracted attention in the context of migraine treatment. The purpose of this study was to investigate the localization and expression of 5-HT 7 receptor in the rat vestibular nuclei by immunohistochemical staining and reverse transcriptase-polymerase chain reaction (RT-PCR). The present study might provide additional insight into the role of 5-HT 7 receptor in the pathogenesis of migraine-related vestibular symptoms.

Background The long-term effects of sibutramine treatment on the rates of cardiovascular events and cardiovascular death among subjects at high cardiovascular risk have not been established. Methods We enrolled in our study 10,744 overweight or obese subjects, 55 years of age or older, with preexisting cardiovascular disease, type 2 diabetes mellitus, or both to assess the cardiovascular consequences of weight management with and without sibutramine in subjects at high risk for cardiovascular events. All the subjects received sibutramine in addition to participating in a weight-management program during a 6-week, single-blind, lead-in period, after which 9804 subjects underwent random assignment in a double-blind fashion to sibutramine (4906 subjects) or placebo (4898 subjects). The primary end point was the time from randomization to the first occurrence of a primary outcome event (nonfatal myocardial infarction, nonfatal stroke, resuscitation after cardiac arrest, or cardiovascular death). Results The mean duration of treatment was 3.4 years. The mean weight loss during the lead-in period was 2.6 kg; after randomization, the subjects in the sibutramine group achieved and maintained further weight reduction (mean, 1.7 kg). The mean blood pressure decreased in both groups, with greater reductions in the placebo group than in the sibutramine group (mean difference, 1.2/1.4 mm Hg). The risk of a primary outcome event was 11.4% in the sibutramine group as compared with 10.0% in the placebo group (hazard ratio, 1.16; 95% confidence interval [CI], 1.03 to 1.31; P=0.02). The rates of nonfatal myocardial infarction and nonfatal stroke were 4.1% and 2.6% in the sibutramine group and 3.2% and 1.9% in the placebo group, respectively (hazard ratio for nonfatal myocardial infarction, 1.28; 95% CI, 1.04 to 1.57; P=0.02; hazard ratio for nonfatal stroke, 1.36; 95% CI, 1.04 to 1.77; P=0.03). The rates of cardiovascular death and death from any cause were not increased. Conclusions Subjects with preexisting cardiovascular conditions who were receiving long-term sibutramine treatment had an increased risk of nonfatal myocardial infarction and nonfatal stroke but not of cardiovascular death or death from any cause. (Funded by Abbott; ClinicalTrials.gov number, NCT00234832.)

OBJECTIVE:: To characterize vestibular and related symptoms seen after blast exposure. STUDY DESIGN:: Prospective single-subject design. SETTINGS:: Tertiary care facility and military field hospital. PATIENTS:: Active-duty US Military personnel exposed to blast(s) in Iraq and/or Afghanistan. INTERVENTIONS:: Vestibular function tests, auditory tests, and a structured history and physical examination. RESULTS:: Blast exposure induced vestibular disorders, and related symptoms are significantly different than those seen in blunt head trauma. The vestibular characteristics and objective tests of vestibular function significantly worsen in blast-exposed patients as a function of time between injury and presentation. CONCLUSION:: Blast exposure produces a unique set of vestibular disorders and associated symptoms that progress over time. Understanding the characteristics of these symptoms as they vary over time may be critical in designing treatment strategies that modify long-term outcome. Language: en

The caudal aspect of the parabrachial nucleus (PBN) contains neurons responsive to whole body, periodic rotational stimulation in alert monkeys (Balaban et al. in J Neurophysiol 88:3175-3193, 2002). This study characterizes the angular and linear motion-sensitive response properties of PBN unit responses during off-vertical axis rotation (OVAR) and position trapezoid stimulation. The OVAR responses displayed a constant firing component which varied from the firing rate at rest. Nearly two-thirds of the units also modulated their discharges with respect to head orientation (re: gravity) during constant velocity OVAR stimulation. The modulated response magnitudes were equal during ipsilateral and contralateral OVARs, indicative of a one-dimensional accelerometer. These response orientations during OVAR divided the units into three spatially tuned populations, with peak modulation responses centered in the ipsilateral ear down, contralateral anterior semicircular canal down, and occiput down orientations. Because the orientation of the OVAR modulation response was opposite in polarity to the orientation of the static tilt component of responses to position trapezoids for the majority of units, the linear acceleration responses were divided into colinear dynamic linear and static tilt components. The orientations of these unit responses formed two distinct population response axes: (1) units with an interaural linear response axis and (2) units with an ipsilateral anterior semicircular canal-contralateral posterior semicircular canal plane linear response axis. The angular rotation sensitivity of these units is in a head-vertical plane that either contains the linear acceleration response axis or is perpendicular to the linear acceleration axis. Hence, these units behave like head-based ('strapdown') inertial guidance sensors. Because the PBN contributes to sensory and interoceptive processing, it is suggested that vestibulo-recipient caudal PBN units may detect potentially dangerous anomalies in control of postural stability during locomotion. In particular, these signals may contribute to the range of affective and emotional responses that include panic associated with falling, malaise associated with motion sickness and mal-de-debarquement, and comorbid balance and anxiety disorders.

Summary Introduction Among deployed U.S. military personnel, a sub-population of international travelers, acute infectious diarrhea continues to be a leading cause of morbidity and a potential threat to military effectiveness. Methods To assess outcomes and satisfaction of diarrhea management in the field, a systematic survey was given to military personnel during mid- or post-deployment from Iraq or Afghanistan, from January through August 2004. Results Sixty-three percent of those surveyed reported at least one episode of diarrhea, while less than half sought care for their symptoms. Overall, trends of decreased post-treatment duration were noted as traveler's diarrhea therapy modalities grew more complex, controlling for severity of illness at presentation. Among those reporting diarrhea, the greatest level of satisfaction was seen in treatment with IV fluids (59%) followed by antibiotics (46%) and loperamide (40%). The greatest amount of dissatisfaction was seen in treatments with oral fluids only. Conclusion While current standard of care is self-treatment of diarrhea in civilian travelers, the U.S. military lacks standards outlining self-treatment of personnel at the individual level. Further research is needed to develop treatment guidelines on diarrhea management during military deployment.

Adaptation is a universal process in organisms as diverse as bacteria and humans, and across the various senses. This article proposes a simple, heuristic, mathematical model containing tonic and phasic processes. The model demonstrates properties not commonly associated with adaptation, such as increased sensitivity to changes, range shifting, and phase lead. Changes in only four parameters permit the model to predict empirical psychophysical data from different senses. The relatively prolonged time courses of responses to oral and topical capsaicin are used to illustrate and validate this mathematical modeling approach for different stimulus profiles. Other examples of phenomena elucidated by this modeling approach include the time courses of taste sensation, brightness perception, loudness perception, cross-adaptation to oral irritants, and cutaneous mechanoreception. It also predicts such apparently unrelated phenomena as perceived alcohol intoxication, habituation, and drug tolerance. Because the integration of phasic and tonic components is a conservative, highly efficacious solution to a ubiquitous biological challenge, sensory adaptation is seen as an evolutionary adaptation, and as a prominent feature of Mother Nature's small bag of tricks.

The aim of this study was to determine whether calcitonin gene-related peptide (CGRP) colocalizes with 5-HT 1F receptor in rat vestibular nuclei using a double immunohistochemical staining procedure. The frequent co-occurrence of migraine and balance disorders suggests a pathophysiologic link between the two. However, the mechanism of migrainous vertigo has not been elucidated, though serotonin (5-HT) and its receptors are believed to involve in the pathogenesis of migrainous vertigo. Furthermore, 5-HT 1F receptor agonists and CGRP receptor antagonists have recently attracted attention as potential treatments for migraine, and CGRP release from trigeminal neurons has been associated with migraine. This study demonstrates the colocalization of 5-HT 1F receptor and CGRP in the rat vestibular nuclei, which suggests that 5-HT 1F receptor regulates the release of CGRP from vestibular nuclei. This finding indicates that 5-HT 1F receptor agonists may ameliorate migrainous vertigo by attenuating elevated levels of CGRP release from vestibular nuclei.

Manganese superoxide dismutase 2 (SOD2) is a key metabolic anti-oxidant enzyme for detoxifying free radicals inside mitochondria. This study documents a gradient in expression of SOD2 by spiral ganglion cells in basal versus apical turn of cochlea that is consistent with differential vulnerability of high frequency hearing to free radical damage. Immunohistochemical methods were used to identify distribution of SOD2 in temporal bone sections from mice, rats, macaques, and humans. In mice and rats, both the proportion of SOD2 immunopositive type 1 spiral ganglion cells and the intensity of immunoreactivity were elevated near cochlear apex. In macaques and humans, the proportion of SO2 immunopositive spiral ganglion cells was equal across cochlear turn, but the intensity of immunoreactivity remained highest for ganglion cells near cochlear apex. Strong SOD2 immunoreactivity was also observed in human type 1 spiral ganglion cells. The average area density of SOD2 immunoreactivity in ganglion cells for each species and cochlear turn showed an allometric relationship with body weight, which is consistent with a conserved basal metabolic characteristic. These findings suggest that spiral ganglion cell responses to ROS exposure may vary along cochlear spiral with lower response capacity at cochlear base contributing to cumulative susceptibility to high frequency hearing loss.

In this article we present a summary of two interactive panel discussions held at the 2008 Council of Emergency Medicine Residency Directors (CORD) annual meeting. Attendees attempted to identify measurable outcomes for resident performance that could be used to evaluate program effectiveness.

We have demonstrated a wireless hydrogen sensing system using commercially available wireless components and AlGaN/GaN high electron mobility transistor (HEMTs) differential sensing diodes as the sensing devices. The active device in the differential pair is coated with 10 nm of Pt to enhance catalytic dissociation of molecular hydrogen, while the reference diode is coated with Ti/Au. Our sensors have a wide range of detection from ppm levels to ∼30%, with the added advantages of a very rapid response time within a couple of seconds, and rapid recovery. The sensors have shown good stability for more than 18 months in an outdoor field test. Currently, the wireless sensing system consists of six wireless sensor nodes and a base station. The wireless sensor node consists of a sensor, a power management system with back-up batteries in case of power outages and a wireless transceiver. The base station consists of a high sensitivity receiver and an in-house developed intelligent monitoring software that does basic data logging and tracking of each individual sensor. The software defines and implements the monitoring states, transitions, and actions of the hydrogen sensor network. Also, the software is able to warn the user of potential sensor failure, power outages and network failures through cell phone network and Internet. Real-time responses of the sensors are displayed through a web site on the Internet. ( http://ren.che.ufl.edu/app/default.aspx ).

We have demonstrated a wireless hydrogen sensing system using commercially available wireless components and AlGaN/GaN High Electron Mobility Transistor (HEMTs) differential sensing diodes as the sensing devices. The active device in the differential pair is coated with 10 nm of Pt to enhance catalytic dissociation of molecular hydrogen, while the reference diode is coated with Ti/Au. Our sensors have a wide range of detection from ppm levels to ~30%, with the added advantages of a very rapid response time within a couple of seconds, and rapid recovery. The sensors have shown good stability for more than 18 months in an outdoor field test.

Study objective The Joint Commission requires "appropriate assessment" of patients presenting with painful conditions. Compliance is usually assessed through retrospective chart analysis. We investigate the discrepancy between observed physician pain assessment and that subsequently documented in the medical record. Methods This was an observational study using a trained investigator watching bedside interactions of emergency physicians. Using a priori definitions, the investigator recorded whether the patient volunteered the presence of pain, physician inquiry about pain, attempts to quantify the pain, treatment offered/rendered, and any assessment of the response to therapy. An independent investigator subsequently assessed the patient's chart for documentation of pain assessment, therapy rendered, and response to treatment. Children younger than 5 years and patients with major trauma, altered mental status, or nontraumatic chest pain were excluded. The institutional review board approved the protocol, the physicians agreed to participate in an "ergonomic study" without knowing the exact nature of data collection, and patients released their records. Results The investigator observed 209 patient encounters. Physicians acknowledged the patients' pain 98.1% of the time but documented its presence in 91.7%. Physicians attempted to quantify the patient's pain in 61.5% of encounters but documented that attempt in only 38.9%. Treatment was offered in 79.9% and recorded in 31.7% of charts. When treatment was offered, the patient's response to the therapy was recorded only 28% of the time. Conclusion Physicians almost always assess and treat patient pain but infrequently record those efforts. The patient's chart is a poor surrogate marker for pain assessment and care by emergency physicians and may not be suitable for use as a compliance assessment tool. Research methodology using retrospective chart analysis may be affected by this phenomenon, suggesting the potential for underestimation of patient pain assessment and treatment by emergency physicians.

The dorsal raphe nucleus (DRN) contains both serotonergic and non-serotonergic projection neurons. Retrograde tracing studies have demonstrated that components of the basal forebrain and extended amygdala are targeted heavily by input from nonserotonergic DRN neurons. The object of this investigation was to examine the terminal distribution of nonserotonergic DRN projections in the basal forebrain and extended amygdala, using a technique that allows selective anterograde tracing of nonserotonergic DRN projections. To trace nonserotonergic DRN projections, animals were pretreated with nomifensine, desipramine and the serotonergic neurotoxin 5,7-dihydroxytryptamine (5,7-DHT), 7 days prior to placing an iontophoretic injection of biotinylated dextran amine (BDA) into the DRN. In animals treated with 5,7-DHT, numerous nonserotonergic BDA-labeled fibers ascended to the basal forebrain in the medial forebrain bundle system. Some of these labeled fibers crossed through the lateral hypothalamus, bed nucleus of the stria terminalis, and substantial innominata. These fibers entered the amygdala through the ansa peduncularis and ramified within the central and basolateral amygdaloid nuclei. Other fibers entered the diagonal band of Broca and formed a dense plexus of labeled fibers in the dorsal half of the intermediate portion of the lateral septal nucleus and the septohippocampal nucleus. These findings demonstrate that the basal forebrain and extended amygdala receive a dense projection from nonserotonergic DRN neurons. Given that the basal forebrain plays a critical role in processes such as motivation, affect, and behavioral control, these findings support the hypothesis that nonserotonergic DRN projections may exert substantial modulatory control over emotional and motivational functions.