Human bipedal instability in tree canopy environments is reduced by "light touch" fingertip support.

Whether tree canopy habitats played a sustained role in the ecology of ancestral bipedal hominins is unresolved. Some argue that arboreal bipedalism was prohibitively risky for hominins whose increasingly modern anatomy prevented them from gripping branches with their feet. Balancing on two legs is indeed challenging for humans under optimal conditions let alone in forest canopy, which is physically and visually highly dynamic. Here we quantify the impact of forest canopy characteristics on postural stability in humans. Viewing a movie of swaying branches while standing on a branch-like bouncy springboard destabilised the participants as much as wearing a blindfold. However "light touch", a sensorimotor strategy based on light fingertip support, significantly enhanced their balance and lowered their thigh muscle activity by up to 30%. This demonstrates how a light touch strategy could have been central to our ancestor's ability to avoid falls and reduce the mechanical and metabolic cost of arboreal feeding and movement. Our results may also indicate that some adaptations in the hand that facilitated continued access to forest canopy may have complemented, rather than opposed, adaptations that facilitated precise manipulation and tool use.

Endogenous cellular prion protein regulates contractility of the mouse ileum.

BACKGROUND: Cellular prion protein (PrP(C) ) is expressed in the enteric nervous system (ENS), however, its physiological role has not been identified. Studies suggest that PrP(C) can function as a metal-binding protein, as absence of the protein has been linked to altered copper metabolism and atypical synaptic activity. Because copper is known to modulate smooth muscle relaxation, we tested the hypothesis that PrP(C) deficiency would alter intestinal contractility. METHODS: We examined electrically evoked ileal contractility in Prnp(-/-) or wild type littermate mice and the effects of copper or copper chelation. PrP(C) expression was studied in whole mount ileal preparations of mice and guinea pigs by immunohistochemistry. KEY RESULTS: Relative to wild type mice, ileal tissues of Prnp(-/-) mice exhibited reduced electrical field stimulation (EFS)-evoked contractility. Furthermore, EFS-induced relaxation, as a percentage of that induced by a nitric oxide donor, was enhanced. Addition of a copper donor to the organ bath increased, whereas the addition of a copper chelator inhibited, nitric oxide donor-induced ileal relaxation in Prnp(-/-) mice. PrP(C) was expressed on nerve fibers or terminals, and some cell bodies in the myenteric and submucosal plexuses of wild type mice. PrP(C) colocalized with a neuron-specific ectonucleotidase, nucleoside triphosphate diphosphohydrolase 3 (NTPDase3), but to only a limited extent with GFAP, a marker of enteric glia. Guinea pigs expressed PrP(C) in nerve fibers or terminals and enteric glia in the myenteric and submucosal plexuses. CONCLUSIONS & INFERENCES: Our findings suggest that PrP(C) , which is abundant in the ENS, has a role in the regulation of ileal contractility.

Feasibility of implementing pulse oximetry screening for congenital heart disease in a community hospital.

OBJECTIVE: Pulse oximetry has been recognized as a promising screening tool for critical congenital heart disease (CCHD). The aim of this research was to study the feasibility of implementation in a community hospital setting. STUDY DESIGN: Meetings were conducted to determine an implementation plan. Pulse oximetry was performed on the right hand and foot after 24 h of age. Newborns with a saturation ≤ 95% or a ≥ 3% difference were considered to have a positive screen. Screening barriers, screening time and ability to effectively screen all eligible newborns were noted. RESULT: From January 2009 through May 2010, of 6841 eligible newborns, 6745 newborns (98.6%) were screened. Of the nine infants with positive pulse oximetry screens, one had CCHD, four had CHD and four others were determined to have false positive screens. Average screening time was 3.5 min (0 to 35 min). CONCLUSION: Pulse oximetry can be implemented successfully in community hospitals without an excessive number of false positives or additional nursing staff.

Assessing the validity of the accelerometry technique for estimating the energy expenditure of diving double-crested cormorants Phalacrocorax auritus.

Over the past few years, acceleration-data loggers have been used to provide calibrated proxies of energy expenditure: the accelerometry technique. Relationships between rate of oxygen consumption and a derivation of acceleration data termed "overall dynamic body acceleration" (ODBA) have now been generated for a range of species, including birds, mammals, and amphibians. In this study, we examine the utility of the accelerometry technique for estimating the energy expended by double-crested cormorants Phalacrocorax auritus to undertake a dive cycle (i.e., a dive and the subsequent pause at the surface before another dive). The results show that ODBA does not calibrate with energy expenditure in diving cormorants, where energy expenditure is calculated from measures of oxygen uptake during surface periods between dives. The possible explanations include reasons why energy expenditure may not relate to ODBA but also reasons why oxygen uptake between dives may not accurately represent energy expenditure during a dive cycle.

A variable parameter single degree-of-freedom model for predicting the effects of sitting posture and vibration magnitude on the vertical apparent mass of the human body.

Models of the vertical apparent mass of the human body are mostly restricted to a sitting posture unsupported by a backrest and ignore the variations in apparent mass associated with changes in posture and changes in the magnitude of vibration. Using findings from experimental research, this study fitted a single degree-of-freedom lumped parameter model to the measured vertical apparent mass of the body measured with a range of sitting postures and vibration magnitudes. The resulting model reflects the effects of reclining a rigid backrest or reclining a foam backrest (from 0 to 30 degrees), the effects of moving the hands from the lap to a steering wheel, the effects of moving the horizontal position of the feet, and the effects of vibration magnitude (from 0.125 to 1.6 ms(-2) r.m.s.). The error between the modelled and the measured apparent mass was minimised, for both the apparent masses of individual subjects and the median apparent masses of groups of 12 subjects, for each sitting posture and each vibration magnitude. Trends in model parameters, the damping ratios, and the damped natural frequencies were identified as a function of the model variables and show the effects of posture and vibration magnitude on body dynamics. For example, contact with a rigid backrest increased the derived damped natural frequency of the principal resonance as a result of reduced moving mass and increased stiffness. When the rigid backrest was reclined from 0 to 30º, the damping decreased and the resonance frequency increased as a result of reduced moving mass. It is concluded that, by appropriate variations in model parameters, a single degree-of-freedom model can provide a useful fit to the vertical apparent mass of the human body over a wide range of postures and vibration magnitudes. When measuring or modelling seat transmissibility, it may be difficult to justify an apparent mass model with more than a single degree-of-freedom if it does not reflect the large influences of vibration magnitude, body posture, and individual variability.

Preliminary trial to investigate temperature of the iPulse intense pulsed light (IPL) glass transmission block during treatment of Fitzpatrick II, IV, V, and VI skin types.

The glass transmission block, a key component of all intense pulsed light (IPL) devices, is responsible for the delivery of IPL energy from the xenon discharge lamp to hair and skin structures during treatment. The purpose of this study was to investigate the variation in temperature of the quartz glass block used in the iPulse (CyDen, Swansea, UK) handset during typical hair removal treatments of Asian and Afro-Caribbean skin types. Initial results from four subjects indicated that the temperature of the glass transmission block did not exceed 45 degrees C during any of the treatments. Furthermore, the development of the temperature measurement methodology described in this paper will enable the comparison of data from different IPL systems to be undertaken in a subsequent larger scale trial.

Glucagon-like peptide-2 induces a specific pattern of adaptation in remnant jejunum.

Glucagon-like peptide-2 (GLP-2) is an enteroendocrine hormone which is uniquely trophic for the intestine; a physiological role in regulating nutrient absorptive capacity is becoming apparent. GLP-2, independent of enteral feeding, stimulates a classical pattern of intestinal adaptation in terminal ileum following resection. Herein we investigate the effects of GLP-2 on the jejunal remant using a rat model of short bowel syndrome (SBS). Juvenile 250- to 275-g SD rats underwent 80% distal small bowel resection, leaving 20 cm of proximal jejunum and venous catheterization. Animals were maintained with total parenteral nutrition (TPN) or TPN+10 microg/kg/hr GLP-2 (n=8 per group). After 7 days, intestinal permeability was assessed by urinary recovery of gavaged carbohydrate probes. Animals were euthanized, and the intestines taken for analysis of morphology, crypt cell proliferation, apoptosis, and expression of SGLT-1 and GLUT-5 transport proteins. GLP-2 treatment reduced intestinal permeability and increased in vivo glucose absorption, small intestinal weight, surface area, villus height, crypt depth, and microvillus height. Intestinal mucosal DNA and protein content per unit length of the small bowel were increased (P < 0.05 for all comparisons). However, in contrast to previous studies examining GLP-2's effects on remnant ileum, the jejunal crypt apoptotic index was increased in GLP-2-treated animals, with no increase in SGLT-1 or GLUT 5 expression. These results show that exogenous GLP-2 treatment of animals with jejunal remnant reduces intestinal permeability, increases glucose absorption, and stimulates morphological features of intestinal adaptation including increased micovillus height and surface area. However, the pattern of changes seen is different from that in remnant ileum. This suggests that GLP-2's effects are specific to different regions of the bowel. Nonetheless, remnant jejunum is responsive to GLP-2 in the absence of enteral nutrition. Further studies are warranted to establish the mechanisms of action and therapeutic potential of GLP-2 in modulating nutrient absorptive capacity.

Gut hormones, and short bowel syndrome: the enigmatic role of glucagon-like peptide-2 in the regulation of intestinal adaptation.

Short bowel syndrome (SBS) refers to the malabsorption of nutrients, water, and essential vitamins as a result of disease or surgical removal of parts of the small intestine. The most common reasons for removing part of the small intestine are due to surgical intervention for the treatment of either Crohn's disease or necrotizing enterocolitis. Intestinal adaptation following resection may take weeks to months to be achieved, thus nutritional support requires a variety of therapeutic measures, which include parenteral nutrition. Improper nutrition management can leave the SBS patient malnourished and/or dehydrated, which can be life threatening. The development of therapeutic strategies that reduce both the complications and medical costs associated with SBS/long-term parenteral nutrition while enhancing the intestinal adaptive response would be valuable. Currently, therapeutic options available for the treatment of SBS are limited. There are many potential stimulators of intestinal adaptation including peptide hormones, growth factors, and neuronally-derived components. Glucagon-like peptide-2 (GLP-2) is one potential treatment for gastrointestinal disorders associated with insufficient mucosal function. A significant body of evidence demonstrates that GLP-2 is a trophic hormone that plays an important role in controlling intestinal adaptation. Recent data from clinical trials demonstrate that GLP-2 is safe, well-tolerated, and promotes intestinal growth in SBS patients. However, the mechanism of action and the localization of the glucagon-like peptide-2 receptor (GLP-2R) remains an enigma. This review summarizes the role of a number of mucosal-derived factors that might be involved with intestinal adaptation processes; however, this discussion primarily examines the physiology, mechanism of action, and utility of GLP-2 in the regulation of intestinal mucosal growth.

Nutrient-stimulated GLP-2 release and crypt cell proliferation in experimental short bowel syndrome.

Glucagon-like peptide-2 (GLP-2) is an enteroendocrine peptide that is released in response to luminal nutrients and has unique trophic actions in the gastrointestinal tract. These features suggest GLP-2 may be important in controlling intestinal adaptation. We examined the relationship over time of GLP-2 production and adaptation to intestinal resection, the effects of resection-induced malabsorption on GLP-2 production, and the correlation of endogenous serum GLP-2 levels with adaptation as measured by crypt-cell proliferation (CCP). We initially examined the effect of nutrient malabsorption, induced by a 90% resection of the proximal intestine studied on day 4, on the time course and levels of GLP-2 release. Secondly, the degree of malabsorption was varied by performing intestinal transection or 50, 75, or 90% resection of proximal small intestine. Finally, the relationship of GLP-2 levels over time with adaptation to a 90% resection was examined by determining GLP-2 levels on days 7, 14, and 28, and correlating this with intestinal adaptation, as assessed by morphology and CCP rate. A 90% resection significantly increased basal and postprandial GLP-2 levels, with a net increase in nutrient-stimulated exposure over 90 min; GLP-2 exposure (integrated levels vs. time) increased 12.7-fold in resected animals (P < 0.001). Basal and postprandial GLP-2 levels significantly correlated with the magnitude of intestinal resection (r(2) = 0.71; P < 0.001), CCP (r(2) = 0.48; P < 0.005), and nutrient malabsorption (protein, P < 0.001; fat, P < 0.005). The increase in CCP was maintained to 28 days after small bowel resection and was associated with an ongoing elevation in GLP-2 release. These findings suggest that GLP-2 is important in initiating and maintaining the small intestinal adaptive response to resection.

The epidemiology of Kawasaki disease in an urban hospital: does African American race protect against coronary artery aneurysms?

The etiology and pathogenesis of Kawasaki disease (KD) is largely unknown. Certain demographic factors and laboratory findings are predictive of the development of coronary artery (CA) aneurysms. The objectives of this study were to determine the epidemiology of KD patients in an urban hospital and determine risk factors associated with their development of CA abnormalities. A longitudinal case series of KD patients admitted to Children's National Medical Center from 1990 to 2002 was examined. Age, sex, ethnic background, duration of fever prior to diagnosis, address, month diagnosed, and CA abnormalities (ectasia or aneurysms) on echocardiography were recorded. Median household income was obtained from the U.S. Census Bureau Web site. The Student t-test, logistic regression analyses, and the Kruskal-Wallis test were used, with significance assumed at p < 0.05. A total of 302 patients were evaluated. CA abnormalties were found in 27 patients (9%), with aneurysms identified in 13 patients (4%). Age was 2.9 +/- 2.4 years (range, 2 months to 14 years). A total of 51 patients (16%) were < or =1 year and 35 patients (12%) were > or =5 years. Ethnic distribution was 54% (164) African American, 24% (72) Caucasian, 9% (29) Asian/Pacific Islander, 8% (23) Hispanic, and 5% (14) Middle Eastern. Only 2/164 (1.2%) African Americans developed CA aneurysms. Neighborhood median income of the cohort was $45,400 +/- $21,200 ($52,200 +/-$25,800 for patients with aneurysms). A total of 28% of cases clustered between December and January. Cases doubled annually in 1999-2001 compared to 1990-1998 (39 vs 19). Multivariate logistic regression found age between 1 and 5 years [p = 0.045; odds ratio, 0.31; 95% confidence interval (CI), 0.10-0.97] and African American race (p = 0.014; odds ratio, 0.15; 95% CI, 0.03-0.68) to be independently protective against CA aneurysms. Duration of fever prior to diagnosis, considered in 210 patients, was different between patients with and without aneurysms (11 +/- 5.3 vs 6.5 +/- 3.8 days, respectively, p = 0.0007). Multivariate logistic regression found fever longer than 5 days to be the only predictive factor associated with the development of aneurysms and any abnormality. African Americans had a shorter duration of fever than the rest of the cohort (6.03 vs 7.31 days), (p = 0.0087). The epidemiology of KD at our hospital is similar to that at other centers except for the predominance of African Americans with a shorter duration of fever prior to diagnosis and a decreased incidence of CA aneurysms compared to other ethnicities. The protective nature of African American ethnicity against the development of CA aneurysms raises speculation about the role of genetics and its interaction with immunity in the pathogenesis of KD.

c-Myc regulates mammalian body size by controlling cell number but not cell size.

Overexpression of the proto-oncogene c-myc has been implicated in the genesis of diverse human tumours. c-Myc seems to regulate diverse biological processes, but its role in tumorigenesis and normal physiology remains enigmatic. Here we report the generation of an allelic series of mice in which c-myc expression is incrementally reduced to zero. Fibroblasts from these mice show reduced proliferation and after complete loss of c-Myc function they exit the cell cycle. We show that Myc activity is not needed for cellular growth but does determine the percentage of activated T cells that re-enter the cell cycle. In vivo, reduction of c-Myc levels results in reduced body mass owing to multiorgan hypoplasia, in contrast to Drosophila c-myc mutants, which are smaller as a result of hypotrophy. We find that c-myc substitutes for c-myc in fibroblasts, indicating they have similar biological activities. This suggests there may be fundamental differences in the mechanisms by which mammals and insects control body size. We propose that in mammals c-Myc controls the decision to divide or not to divide and thereby functions as a crucial mediator of signals that determine organ and body size.

Iloprost suppresses connective tissue growth factor production in fibroblasts and in the skin of scleroderma patients.

Patients with scleroderma receiving Iloprost as a treatment for severe Raynaud's phenomenon report a reduction in skin tightness, suggesting that this drug inhibits skin fibrosis. Connective tissue growth factor (CTGF), a recently described profibrotic cytokine, acts downstream and in concert with TGF-beta to stimulate the fibrotic process and is involved in the fibrosis seen in scleroderma. Here we show that Iloprost, acting by elevation of cAMP, blocks the induction of CTGF and the increase in collagen synthesis in fibroblasts exposed to TGF-beta. The potency of Iloprost with respect to suppression of CTGF far exceeds that of other prostanoid receptor agonists, suggesting that its effect is mediated by the prostacyclin receptor IP. By sampling dermal interstitial fluid using a suction blister device, we show that CTGF levels are greatly elevated in the dermis of scleroderma patients compared with healthy controls and that Iloprost infusion causes a marked decrease in dermal CTGF levels. These studies suggest that Iloprost could be reducing the level of a key profibrotic cytokine in scleroderma patients and that endogenous production of eicosanoids may limit the fibrotic response to TGF-beta.

Visual fields and foraging in procellariiform seabirds: sensory aspects of dietary segregation.

Retinal visual fields were determined using an ophthalmoscopic reflex technique in two seabird species of the family Procellariidae: white-chinned petrel Procellaria aequinoctialis and antarctic prion Pachyptila desolata. The binocular fields of both species show a similar shape but they differ in size and in the position of the bill within the field. In white-chinned petrels the binocular field extends vertically through approximately 140 degrees and has a maximum width of approximately 40 degrees. The bill is placed approximately central within the field. The binocular field of the prions is approximately half this width and vertical extent, and the bill is placed close to the ventral edge. These differences in binocular field topography can be correlated with the different foraging techniques that these birds employ when seeking a similar diet within the same environment. White-chinned petrels pursue individual items both at the surface and while diving to moderate depths. Antarctic prions feed primarily by filtering items from surface waters. These differences in visual field topography mirror those found in different terrestrial bird species that primarily employ visual or tactile cues in the pursuit of food items. White-chinned petrel eyes and visual fields show features of an amphibious optical design similar to those found in penguins and albatrosses.

In vivo measurement of intestinal absorption using 3-0 methylglucose in short bowel syndrome.

PURPOSE: The management of patients with short bowel syndrome is complicated by the paucity of methods to assess in vivo the absorptive capacity of the remaining bowel. The purpose of this experiment was to assess the feasibility of using urinary recovery of 3-0 methylglucose (3-0 MG) as a quantitative measure of carbohydrate absorptive capacity, comparing it with in vivo absorption and in vitro glucose transport studies. METHODS: Male Sprague Dawley rats underwent either a 90% proximal small bowel resection or sham resection (n = 8 in each group). Animals were pair fed, weighed, and followed up for 14 days. A 3-day balance study was done, measuring feed intake and fecal output for percentages of fat and energy absorption. Animals were gavaged with 3-0 MG/Mannitol solution, and 4-hour urinary recovery of sugars was assessed using high-performance liquid chromatography (HPLC). On different days these studies were repeated with increasing amounts of added normal glucose (1 mol/L, 1.25 mol/L, and 1.5 mol/L) in the gavage solution given to compete for 3-0 MG transport, and thus increase the "sensitivity" of the test. Animals were then killed, and sections of intestine taken for in vitro assessment of glucose transport using radiolabeled 3-0 MG in Ussing chambers. RESULTS: Total energy, carbohydrate, and fat absorption all were reduced significantly in the resected animals, as was 3-0 MG urinary recovery (62.9 +/- 10.5%) in controls versus (35.8 +/- 17.5%) in resected animals (P <.05). 3-0 MG urinary recovery correlated well with dietary carbohydrate absorption (r = 0.74), and with Ussing chamber measures of glucose flux (r = 0.97). Adding exogenous glucose to the test solution to "compete" for 3-0 MG transport sites did not improve sensitivity. CONCLUSIONS: These results show that 3-0 MG is useful in measuring nutrient absorption capacity in rats after massive small bowel resection. Further studies to validate these methods in human patients with short bowel syndrome are suggested.

Investigations into migraine pathogenesis: time course for effects of m-CPP, BW723C86 or glyceryl trinitrate on appearance of Fos-like immunoreactivity in rat trigeminal nucleus caudalis (TNC).

Clinical and preclinical studies suggest that 5-HT and nitric oxide (NO) mobilization within the trigeminovascular system is fundamental to the initiation of migraine attacks., e.g. m-chlorophenylpiperazine (m-CPP) and glyceryl trinitrate (GTN) induce headache in humans. 5-HT2B receptors are known to mediate NO-dependent vasorelaxation in peripheral blood vessels, raising the possibility that this receptor is implicated in the pathogenesis of the disease. Therefore, we measured the effects of 5-HT2B agonists (m-CPP or BW723C86) or GTN on trigeminal nerves by quantifying Fos expression in the rat TNC. m-CPP (0.1 mg/kg, i.v.) induced time-dependent elevations in Fos-LI in the rat TNC 2 h and 8 h after injection. In contrast, neither intravenous GTN (0.5 microg/kg per min, infused 20 min) nor BW723C86 (0.1 mg/kg, i.v.) increased Fos-LI at 2 h or 8 h after administration. These data are not consistent with the involvement of the 5-HT2B/2C receptors or NO in trigeminovascular activation, and by inference migraine, and suggest the contribution of some other unidentified pathway.

Discovery of 4-[3-(trans-3-dimethylaminocyclobutyl)-1H-indol-5-ylmethyl]-(4S)-oxazolidin-2-one (4991W93), a 5HT(1B/1D) receptor partial agonist and a potent inhibitor of electrically induced plasma extravasation.

Utilizing a pharmacophoric model of binding of 3-(2-aminoethyl)indoles to 5HT(1B/1D) receptors, we identified the 3-aminocyclobutyl group as a potential ethylamine isostere. A novel multidimensional chemometric approach was used to predict the intrinsic activity (degree of agonism) at the receptor. A qualitative model for pharmacokinetic properties was then used to guide the synthesis toward molecules likely to have oral bioavailability in humans. A novel synthetic route to 3-(3-dimethylaminocyclobutyl)indoles was developed. Analogues showed generally lower intrinsic activity at 5HT(1B/1D) receptors than their ethylamine counterparts. 4-[3-(trans-3-Dimethylaminocyclobutyl)-1H-indol-5-ylmethyl]-(4S)-oxazolidin-2-one (4991W93, 1) was identified as a partial agonist against 5HT(1B/1D) receptors, with low intrinsic activity. This molecule also has significant activity against 5HT(1F) receptors but is selective over other 5HT receptors. In addition this compound was found to be an exceptionally potent inhibitor of electrically induced plasma extravasation. Compound 1 may have utility in the treatment and prophylaxis of migraine.