Intensity-dependent effects of aerobic training on pressure pain threshold in overweight men: A randomized trial.

PURPOSE: To investigate the chronic and acute effects of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) on pressure pain thresholds (PPT) in overweight men. METHODS: Twenty-eight participants performed stationary cycling exercise three times per week for 6 weeks. Participants were randomly allocated to HIIT (10 × 1-min intervals at 90% peak heart rate) or MICT (30 min at 65-75% peak heart rate). PPTs were assessed over the rectus femoris, tibialis anterior and upper trapezius before and after the 6-week training programme (chronic effect) as well as before and after the first, middle and final exercise sessions (acute effect). RESULTS: For chronic exercise, PPTs increased more after MICT compared to HIIT over the rectus femoris (p = 0.009, effect size r = 0.54) and tibialis anterior (p = 0.012, r = 0.54), but not the trapezius (p = 0.399, r = 0.29). The effect of acute exercise on PPT was more varied and ranged from moderate hypoalgesia to moderate hyperalgesia. Overall, however, there was no consistent change in PPT after acute exercise for HIIT or MICT (p ≥ 0.231, r ≥ -0.31 and ≤0.31). CONCLUSION: Six weeks of MICT cycling (chronic exercise) increased PPT for the lower body, but not upper body, in overweight men, whereas HIIT did not provide any hypoalgesic effect for chronic exercise. The acute effect of exercise on PPT was highly variable and negligible overall. SIGNIFICANCE: This study shows that aerobic training increases pressure pain threshold in pain-free adults. This effect was observed only for MICT over-exercised muscles, implying intensity- and site-specific effects of exercise training on pain threshold.

Largest GWAS of PTSD (N=20 070) yields genetic overlap with schizophrenia and sex differences in heritability.

The Psychiatric Genomics Consortium-Posttraumatic Stress Disorder group (PGC-PTSD) combined genome-wide case-control molecular genetic data across 11 multiethnic studies to quantify PTSD heritability, to examine potential shared genetic risk with schizophrenia, bipolar disorder, and major depressive disorder and to identify risk loci for PTSD. Examining 20 730 individuals, we report a molecular genetics-based heritability estimate (h2SNP) for European-American females of 29% that is similar to h2SNP for schizophrenia and is substantially higher than h2SNP in European-American males (estimate not distinguishable from zero). We found strong evidence of overlapping genetic risk between PTSD and schizophrenia along with more modest evidence of overlap with bipolar and major depressive disorder. No single-nucleotide polymorphisms (SNPs) exceeded genome-wide significance in the transethnic (overall) meta-analysis and we do not replicate previously reported associations. Still, SNP-level summary statistics made available here afford the best-available molecular genetic index of PTSD-for both European- and African-American individuals-and can be used in polygenic risk prediction and genetic correlation studies of diverse phenotypes. Publication of summary statistics for ∼10 000 African Americans contributes to the broader goal of increased ancestral diversity in genomic data resources. In sum, the results demonstrate genetic influences on the development of PTSD, identify shared genetic risk between PTSD and other psychiatric disorders and highlight the importance of multiethnic/racial samples. As has been the case with schizophrenia and other complex genetic disorders, larger sample sizes are needed to identify specific risk loci.

White Matter Changes Related to Subconcussive Impact Frequency during a Single Season of High School Football.

BACKGROUND AND PURPOSE: The effect of exposing the developing brain of a high school football player to subconcussive impacts during a single season is unknown. The purpose of this pilot study was to use diffusion tensor imaging to assess white matter changes during a single high school football season, and to correlate these changes with impacts measured by helmet accelerometer data and neurocognitive test scores collected during the same period. MATERIALS AND METHODS: Seventeen male athletes (mean age, 16 ± 0.73 years) underwent MR imaging before and after the season. Changes in fractional anisotropy across the white matter skeleton were assessed with Tract-Based Spatial Statistics and ROI analysis. RESULTS: The mean number of impacts over a 10-g threshold sustained was 414 ± 291. Voxelwise analysis failed to show significant changes in fractional anisotropy across the season or a correlation with impact frequency, after correcting for multiple comparisons. ROI analysis showed significant (P < .05, corrected) decreases in fractional anisotropy in the fornix-stria terminalis and cingulum hippocampus, which were related to impact frequency. The effects were strongest in the fornix-stria terminalis, where decreases in fractional anisotropy correlated with worsening visual memory. CONCLUSIONS: Our findings suggest that subclinical neurotrauma related to participation in American football may result in white matter injury and that alterations in white matter tracts within the limbic system may be detectable after only 1 season of play at the high school level.

Practices and outcomes of self-treatment with helminths based on physicians' observations.

The successful use of helminths as therapeutic agents to resolve inflammatory disease was first recorded 40 years ago. Subsequent work in animal models and in humans has demonstrated that the organisms might effectively treat a wide range of inflammatory diseases, including allergies, autoimmune disorders and inflammation-associated neuropsychiatric disorders. However, available information regarding the therapeutic uses and effects of helminths in humans is limited. This study probes the practices and experiences of individuals 'self-treating' with helminths through the eyes of their physicians. Five physicians monitoring more than 700 self-treating patients were interviewed. The results strongly support previous indications that helminth therapy can effectively treat a wide range of allergies, autoimmune conditions and neuropsychiatric disorders, such as major depression and anxiety disorders. Approximately 57% of the self-treating patients observed by physicians in the study had autism. Physicians reported that the majority of patients with autism and inflammation-associated co-morbidities responded favourably to therapy with either of the two most popular organisms currently used by self-treaters, Hymenolepis diminuta and Trichuris suis. However, approximately 1% of paediatric patients experienced severe gastrointestinal pains with the use of H. diminuta, although the symptoms were resolved with an anti-helminthic drug. Further, exposure to helminths apparently did not affect the impaired comprehension of social situations that is the hallmark of autism. These observations point toward potential starting points for clinical trials, and provide further support for the importance of such trials and for concerted efforts aimed at probing the potential of helminths, and perhaps other biologicals, for therapeutic use.

Inter-site and inter-scanner diffusion MRI data harmonization.

We propose a novel method to harmonize diffusion MRI data acquired from multiple sites and scanners, which is imperative for joint analysis of the data to significantly increase sample size and statistical power of neuroimaging studies. Our method incorporates the following main novelties: i) we take into account the scanner-dependent spatial variability of the diffusion signal in different parts of the brain; ii) our method is independent of compartmental modeling of diffusion (e.g., tensor, and intra/extra cellular compartments) and the acquired signal itself is corrected for scanner related differences; and iii) inter-subject variability as measured by the coefficient of variation is maintained at each site. We represent the signal in a basis of spherical harmonics and compute several rotation invariant spherical harmonic features to estimate a region and tissue specific linear mapping between the signal from different sites (and scanners). We validate our method on diffusion data acquired from seven different sites (including two GE, three Philips, and two Siemens scanners) on a group of age-matched healthy subjects. Since the extracted rotation invariant spherical harmonic features depend on the accuracy of the brain parcellation provided by Freesurfer, we propose a feature based refinement of the original parcellation such that it better characterizes the anatomy and provides robust linear mappings to harmonize the dMRI data. We demonstrate the efficacy of our method by statistically comparing diffusion measures such as fractional anisotropy, mean diffusivity and generalized fractional anisotropy across multiple sites before and after data harmonization. We also show results using tract-based spatial statistics before and after harmonization for independent validation of the proposed methodology. Our experimental results demonstrate that, for nearly identical acquisition protocol across sites, scanner-specific differences can be accurately removed using the proposed method.

Fear learning circuitry is biased toward generalization of fear associations in posttraumatic stress disorder.

Fear conditioning is an established model for investigating posttraumatic stress disorder (PTSD). However, symptom triggers may vaguely resemble the initial traumatic event, differing on a variety of sensory and affective dimensions. We extended the fear-conditioning model to assess generalization of conditioned fear on fear processing neurocircuitry in PTSD. Military veterans (n=67) consisting of PTSD (n=32) and trauma-exposed comparison (n=35) groups underwent functional magnetic resonance imaging during fear conditioning to a low fear-expressing face while a neutral face was explicitly unreinforced. Stimuli that varied along a neutral-to-fearful continuum were presented before conditioning to assess baseline responses, and after conditioning to assess experience-dependent changes in neural activity. Compared with trauma-exposed controls, PTSD patients exhibited greater post-study memory distortion of the fear-conditioned stimulus toward the stimulus expressing the highest fear intensity. PTSD patients exhibited biased neural activation toward high-intensity stimuli in fusiform gyrus (P<0.02), insula (P<0.001), primary visual cortex (P<0.05), locus coeruleus (P<0.04), thalamus (P<0.01), and at the trend level in inferior frontal gyrus (P=0.07). All regions except fusiform were moderated by childhood trauma. Amygdala-calcarine (P=0.01) and amygdala-thalamus (P=0.06) functional connectivity selectively increased in PTSD patients for high-intensity stimuli after conditioning. In contrast, amygdala-ventromedial prefrontal cortex (P=0.04) connectivity selectively increased in trauma-exposed controls compared with PTSD patients for low-intensity stimuli after conditioning, representing safety learning. In summary, fear generalization in PTSD is biased toward stimuli with higher emotional intensity than the original conditioned-fear stimulus. Functional brain differences provide a putative neurobiological model for fear generalization whereby PTSD symptoms are triggered by threat cues that merely resemble the index trauma.

The success of 6-hour hospital discharge on patients having vaginal repair operations using a new conscious sedation technique.

Anterior and posterior repair are standard surgical techniques for treatment of vaginal prolapse. These procedures are performed traditionally under general anaesthetic or spinal anaesthetic and usually require overnight admission in the hospital. We describe our case series of 40 patients who underwent anterior (18/40), posterior (20/40) or combined repair (2/40) under local anaesthetic and conscious sedation (Remifentanyl). The majority (35/40) were performed in the day-case surgery unit and 95% patients were discharged within 6 hours of the operation, with no complications. All the patients were satisfied with the anaesthetic technique. We concluded that our technique of vaginal repair avoids the risk of general and spinal anaesthetic. The majority of operations can be performed as day cases with good patient satisfaction and without increasing risks to the patients. This technique has potential significant financial saving for the hospitals.

Natural binders and solid bridge type binding mechanisms in briquettes and pellets made from corn stover and switchgrass.

Corn stover and switchgrass are two important feedstocks considered for producing renewable fuels and energy in the US. Densification of these biomass feedstocks into briquettes/pellets would help reduce the problems and costs of bulk transportation, handling, and storage of biomass feedstocks. In this study, the role of the natural binders in corn stover and switchgrass to make durable particle-particle bonding in briquettes/pellets was investigated by micro-structural analyses. Scanning Electron Microscopy (SEM) images of briquettes made by using a uniaxial piston-cylinder densification apparatus in the laboratory, briquettes made by using a pilot-scale roll-press briquetting machine, and pellets made by using a pilot-scale conventional ring-die pelleting machine were analysed. The SEM images showed that the bonding between particles was created mainly through solid bridges. The solid bridges between particles were made by natural binders in the biomass expressed during the densification process. UV auto-fluorescence images of briquettes and pellets further confirmed that the solid bridges were made mainly by natural binders such as lignin and protein. It was found that activating (softening) the natural binders using moisture and temperature in the range of glass transition is important to make durable particle-particle bonding.

Comment on "Carbon-negative biofuels from low-input high-diversity grassland biomass".

Tilman et al. (Reports, 8 December 2006, p. 1598) argued that low-input high-diversity grasslands can provide a substantial proportion of global energy needs. We contend that their conclusions are not substantiated by their experimental protocol. The authors understated the management inputs required to establish prairies, extrapolated globally from site-specific results, and presented potentially misleading energy accounting.

Mortality of Indianmeal moth (Lepidoptera: Pyralidae) populations under fluctuating low temperatures: model development and validation.

A model for predicting mortality of Indianmeal moth larvae [Plodia interpunctella (Hübner) (Lepidoptera: Pyralidae)] under fluctuating low-temperature conditions was developed. The time and temperature combinations required to achieve 100% mortality of field-collected, cold-acclimated P. interpunctella larvae obtained from laboratory mortality experiments were used to develop the mortality model. Accumulation of mortality rate over time was called the cumulative lethality index (CLI). Complete mortality of insect populations would occur when CLI equals 1. Observed mortality of field-collected, cold-acclimated P. interpunctella larvae in five 76.2-T (3,000-bu) shelled corn bins located in Rosemount, MN, during the winters of 2003-2004 and 2004-2005 were used to validate the CLI model (i.e., mortality model). Excellent agreement between predicted and measured time to 100% larval mortality was observed. The CLI model would be useful for developing low-temperature aeration management strategies for controlling overwintering P. interpunctella in grain bins. In addition, this model will be useful when determining if additional control measures will be required as a result of above-seasonal ambient temperatures.

Reclassification of Leptospira parva Hovind-Hougen et al. 1982 as Turneriella parva gen. nov., comb. nov.

Analysis of the G+C content, DNA-DNA relatedness to other leptospires and 16S rRNA gene sequence of Leptospira parva showed that this species was not related to other Leptospira species. On the basis of these data, it is proposed that Leptospira parva should be transferred to the genus Turneriella as Turneriella parva gen. nov., comb. nov., with strain H(T) (=NCTC 11395(T)=ATCC BAA-1111(T)) as the type strain.

Relationship between supercooling point and mortality at low temperatures in Indianmeal moth (Lepidoptera: Pyralidae).

Indianmeal moth, Plodia interpunctella (Hübner), is classified as a freeze-intolerant organism and one of the most cold-tolerant stored-product pests. The objective of this study was to determine the relationship between mortality at low temperatures after minimum exposure and the supercooling point (SCP) for laboratory-reared P. interpunctella at different stages of development. This relationship also was analyzed for field-collected, cold-acclimated fifth instars. Mean SCP of laboratory-reared larvae (i.e., feeding stage) was consistently above approximately -16 degrees C. Mean SCP of laboratory-reared pupae and adults (i.e., nonfeeding stages) and field-collected, cold-acclimated fifth instars was consistently below approximately -21 degrees CP seemed to be the boundary between survival and death for larvae. However, it seemed that a 1-min exposure was not sufficient to cause larval mortality at the SCP. Alternatively, for both pupae and adults, the SCP seemed not to play an important role in their survival at low temperatures, with significant mortality observed at temperatures higher than the mean SCP. Adults were the most susceptible to low temperatures with no survival occurring at -20 degrees C, > 3 degrees C above its mean SCP. Results of this investigation demonstrate that P. interpunctella has a different response to low temperatures depending on stage of development and cold acclimation. Classifying P. interpunctella only as a freeze-intolerant organism disregards the occurrence of prefreeze mortality in this species. Therefore, a reclassification of this species (e.g., chill tolerant or chill susceptible) based on the extent of prefreeze mortality and the temperature and time of exposure at which it occurs is suggested.

A simple method to adjust cooling rates for supercooling point determination.

A simple method to obtain predetermined constant cooling rates for insect supercooling point (SCP) determination is described. A transient heat transfer equation was used to design polystyrene cubes of different sizes to yield constant rates of cooling at their centers when held at a constant surrounding temperature. Cubes of 0.29 x 0.29 x 0.29 m and 0.19 x 0.19 x 0.19 m were found to produce cooling rates of about -0.5 and -1 degree C per min, respectively, from 0 to -40 degree C. The observed temperature variations at the geometrical center of the cubes were similar to those predicted by the equation. Temperature plots showed a nearly constant rate of cooling. Supercooling points of Tribolium castaneum (Herbst) at different stages of development were recorded using polystyrene cubes. These SCPs compared favorably with published values. This method of obtaining cooling rates is economical, flexible, and allows for multiple simultaneous SCP measurements.

Seepage from deep bedded and poultry litter systems.

The work reported indicates that there could be a potential of ground water pollution by NO3-N from turkey facilities built on both sandy and clay soils. At four different depths (30.54, 61.08, 91.62, and 122.16 cm), the NO3-N levels for the clay soil were 1572, 497, 66, and 28 ppm, and those for the sandy soil were 293, 425, 324, and 164 ppm, respectively. No significant P increases were observed but there did exist a significant increase of K in the topsoil for both clay and sandy turkey structures. The results show that swine hoop houses with less than three or four years of age may not pose a threat to groundwater pollution due to the leaching of nutrients. The only dairy feedlot sampled in this study, although it has been used for more than 20 years, did not show leaching of NO3-N and P. However, it did show a significantly elevated concentration of potassium in the topsoil, as compared to the background sample. More sites should be investigated to verify this.

Assessing the operating efficiencies of teaching hospitals by an enhancement of the AHA/AAMC method. American Hospital Association/Association of American Medical Colleges.

In the ongoing effort to control costs, comparisons among hospitals' efficiency levels, if valid, can help identify "best practices" across institutions and uncover situations that need corrective intervention. The authors present an extension of the "adjusted cost per equivalent discharge" approach, which incorporates case-mix-severity differences, regional labor cost differentials, and inpatient/outpatient mix, but does not take into account such factors as the differences in hospital sizes, extents of the teaching mission, or quality of care delivered. The alternative approach yields information that suggests where an institution's total operating costs might be reduced with no change in any of the hospital's outputs or operating environment, through comparison with a "peer group" of other hospitals, matched according to the subject hospital's number of beds, the quality of care the hospital delivers, the extent of medical education carried out, the level of case-mix-adjusted discharges, and outpatient activities. A difficulty with this approach (as with others) is that measurement of some of the additional facets (e.g., quality of care) is still evolving, so its main contribution at this time is to provide a construct and method capable of incorporating these important added considerations. Hospital rankings achieved by applying the current and alternative approaches to a real set of teaching hospitals operating in FY 1987 are compared. While the rankings produced by the two approaches are loosely similar, the authors show that some significant differences do appear and can be at least partially explained by the incorporation of the additional factors mentioned above.

Concentration- and time-dependent upregulation and release of the cytokines MIP-2, KC, TNF, and MIP-1alpha in rat alveolar macrophages by fungal spores implicated in airway inflammation.

Inhalation of fungal spores has been shown to cause primary or secondary infection and respiratory inflammation and diseases such as allergic alveolitis, atopic asthma, and organic dust toxic syndrome, which are rarely reported in the absence of predisposing factors. Biochemical and molecular markers of inflammation were measured in rat bronchial alveolar lavage cells (> 95% macrophages) following stimulation with fungal spores isolated from pathogenic and nonpathogenic fungi that have been implicated in airway inflammation. The results of this study demonstrate that mRNA transcripts for the C-X-C branch of the PF4 superfamily are differentially upregulated over those of the C-C mediators in a time- and concentration-dependent manner. Macrophage inflammatory protein (MIP)-2 and KC were differentially upregulated over the acute phase inflammatory cytokines MIP-1alpha and tumor necrosis factor-alpha (TNF-alpha) in rat alveolar macrophages stimulated with fungal spores from Aspergillus candidus, Aspergillus niger, Eurotium amstelodami, and Cladosporium cladosporioides. Spores from Aspergillus terreus and Penicillium spinulosum failed to stimulate an increase of any cytokine mRNA, whereas those from Aspergillus fumigatus stimulated the upregulation of MIP-2, KC, TNF-alpha, and MIP-1alpha mRNAs. Over time, A. fumigatus stimulated increasing KC production until 24 h, when production levels increased slightly, then leveled off when measurements ceased at 36 h. Latex spheres stimulated modest amounts of MIP-2 and transforming growth factor-beta only. These observations suggest that the inflammatory cytokines MIP-2 and KC may be involved in the inflammation arising from the inhalation of fungal spores in a time- and concentration-dependent manner.

Blood pressure and fetal heart rate changes with patient-controlled combined spinal epidural analgesia while ambulating in labour.

OBJECTIVE: To determine the effect of patient-controlled combined spinal epidural analgesia (PCEA) on maternal pulse and blood pressure, and fetal heart rate in primigravid women, when adapting different positions in labour. DESIGN: A prospective study. SETTING: Queen Charlotte's and Chelsea hospital, London. PARTICIPANTS: Fifty-five primigravid women in labour at > or = 37 weeks of gestation; 40 women had supervised standing top-ups given by an anaesthetist. A further 15 women had PCEA top-ups given in each of standing, sitting and lying positions. MAIN OUTCOME MEASURES: Maternal pulse rate, blood pressure and fetal heart rate changes following epidural top-ups. RESULTS: In the first 40 women there was no clinically significant fall in their blood pressure (< 5 mmHg). The subsequent 15 women who had PCEA top-ups had no fall in blood pressure in the standing and sitting positions, though the average blood pressure fell significantly when a top-up was given in the lying position. Maternal heart rate increased significantly at 12 min post top-up when the women were in the standing position (P = 0.0018). In the 15 women who had PCEA top-ups, the CTG showed improvement in decelerations when women were in the standing position but deterioration when in the lying position (P < 0.01). CONCLUSION: Patient-controlled epidural analgesia top-ups with maternal mobility may be beneficial to the fetus possibly by reducing the hypotension normally associated with top-ups in the lying position.

Estimating the hospital-wide cost differentials warranted for teaching hospitals. An alternative to regression approaches.

Under Medicare's Prospective Payment System, teaching hospitals receive additional reimbursements, vis-à-vis nonteaching hospitals, for both "direct" teaching expenses and for "indirect" expenses. They totaled $3.1 billion in fiscal year 1989. The authors propose and illustrate a non-regression-based, nonparametric method for viewing the total hospital-wide reimbursement differential warranted for teaching hospitals, a method utilizing a peer grouping of like hospitals to estimate two different "best practices" cost frontiers. The hospital's efficiently delivered cost to meet all of the hospital's actual service outputs, including its teaching mission, and delivered level of quality of care, is compared to the corresponding cost when only the teaching mission is excluded. The difference in these costs for a particular hospital can be used to estimate a suggested lump sum Medicare reimbursement add-on, in recognition of the hospital's teaching mission. The approach is illustrated using a subset of the Health Care Financing Administration's 1988 hospital data set, with comparisons of actual and suggested reimbursements provided.

The trade-off between hospital cost and quality of care. An exploratory empirical analysis.

The debate concerning quality of care in hospitals, its "value" and affordability, is increasingly of concern to providers, consumers, and purchasers in the United States and elsewhere. We undertook an exploratory study to estimate the impact on hospital-wide costs if quality-of-care levels were varied. To do so, we obtained costs and service output data regarding 300 U.S. hospitals, representing approximately a 5% cross section of all hospitals operating in 1983; both inpatient and outpatient services were included. The quality-of-care measure used for the exploratory analysis was the ratio of actual deaths in the hospital for the year in question to the forecasted number of deaths for the hospital; the hospital mortality forecaster had earlier (and elsewhere) been built from analyses of 6 million discharge abstracts, and took into account each hospital's actual individual admissions, including key patient descriptors for each admission. Such adjusted death rates have increasingly been used as potential indicators of quality, with recent research lending support for the viability of that linkage. The authors then utilized the economic construct of allocative efficiency relying on "best practices" concepts and peer groupings, built using the "envelopment" philosophy of Data Envelopment Analysis and Pareto efficiency. These analytical techniques estimated the efficiently delivered costs required to meet prespecified levels of quality of care. The marginal additional cost per each death deferred in 1983 was estimated to be approximately $29,000 (in 1990 dollars) for the average efficient hospital. Also, over a feasible range, a 1% increase in the level of quality of care delivered was estimated to increase hospital cost by an average of 1.34%. This estimated elasticity of quality on cost also increased with the number of beds in the hospital.