The Morphology of Corneal Cap and Its Relation to Refractive Outcomes in Femtosecond Laser Small Incision Lenticule Extraction (SMILE) with Anterior Segment Optical Coherence Tomography Observation

Purpose

To investigate the morphology of corneal caps in femtosecond laser small incision lenticule extraction (SMILE) and its relation to the refractive outcomes.

Methods

A prospective study of fifty-four corneal caps created with VisuMax femtosecond laser were examined using an Fourier-domain optical coherence tomography at 1 day, 1 week, 1 month and 6 months after SMILE. The cap thickness at nine points on each of the four meridians (0°, 45°, 90°, 135°) and the diameter were measured. Cap morphology, changes over time and its correlation with refractive outcomes were assessed.

Results

The mean achieved central cap thickness were (108.74±5.06) µm at 6 months and (107.32±4.81 ) µm at 1 month postoperatively, significantly thinner than that at 1 day (110.81±7.95) µm and 1 week (109.58±7.48 ) µm (P<0.05). The mean diameter on 0° meridian was (7.61±0.07) mm, significantly larger than that on 90° meridian (7.57±0.06) mm (P = 0.001). Cap morphology showed good regularity, except that the differences of points in two pairs were significant at 1 day postoperatively. The uniformity was consistent over time and the central cap thickness was thinner than those in the paracentral and peripheral areas. The refractive outcomes stabilized within 1 month. Uncorrected distance visual acuity (UDVA) was correlated to the central cap thickness at 1 day and 1 week (both r_s = 0.33, p<0.05). The uniformity index was correlated with UDVA (r_s = 0.34, p<0.05) and corrected distance visual acuity (r_s = 0.32, p<0.05) at 1 week postoperatively.

Conclusions

Corneal caps of SMILE are predictable with good reproducibility, regularity and uniformity. Cap morphology might have a mild effect on refractive outcomes in the early stage. Further study should focus on the impact on the visual quality.     

Long-Term Prognostic Value of Restitution Slope in Patients with Ischemic and Dilated Cardiomyopathies

Background

An action potential duration (APD) restitution curve with a steep slope ≥1 has been associated with increased susceptibility for malignant ventricular arrhythmias. We aimed to evaluate the “restitution hypothesis” and tested ventricular APD restitution slope as well as effective refractory period (ERP)/APD ratio for long-term prognostic value in patients with ischemic (ICM) or dilated cardiomyopathy (DCM).

Methodology/Principal Findings

Monophasic action potentials were recorded in patients with ICM (n = 32) and DCM (n = 42) undergoing routine programmed ventricular stimulation (PVS). Left ventricular ejection fraction was 32±7% and 28±9%, respectively. APD and ERP were measured at baseline stimulation (S₁) and upon introduction of one to three extrastimuli (S₂–S₄). ERP/APD ratios and the APD restitution curve were calculated and the maximum restitution slope was determined. After a mean follow-up of 6.1±3.0 years, the combined end-point of mortality and and/or implantable cardioverter-defibrillator shock was not predicted by restitution slope or ERP/APD ratios. Comparing S₂ vs. S₃ vs. S₄ extrastimuli for restitution slope (1.5±0.6 vs. 1.4±0.4 vs. 1.3±0.5; p = NS), additional extrastimuli did not lead to a steepening restitution slope. ERP/APD ratio decreased with additional extrastimuli (0.98±0.09 [S₁] vs. 0.97±0.10 [S₂] vs. 0.93±0.11 [S₃]; p = 0.03 S₁ vs. S₃). Positive PVS was strongly predictive of outcome (p = 0.006).

Conclusions/Significance

Neither ventricular APD restitution slope nor ERP/APD ratios predict outcome in patients with ICM or DCM.     

Characteristics of Glucose Metabolism in Nordic and South Asian Subjects with Type 2 Diabetes

Background

Insulin resistance and type 2 diabetes are more prevalent in people of South Asian ethnicity than in people of Western European origin. To investigate the source of these differences, we compared insulin sensitivity, insulin secretion, glucose and lipid metabolism in South Asian and Nordic subjects with type 2 diabetes.

Methods

Forty-three Nordic and 19 South Asian subjects with type 2 diabetes were examined with intra-venous glucose tolerance test, euglycemic clamp including measurement of endogenous glucose production, indirect calorimetry measuring glucose and lipid oxidation, and dual x-ray absorptiometry measuring body composition.

Results

Despite younger mean ± SD age (49.7±9.4 vs 58.3±8.3 years, p = 0.001), subjects of South Asian ethnicity had the same diabetes duration (9.3±5.5 vs 9.6±7.0 years, p = 0.86), significantly higher median [inter-quartile range] HbA_1c (8.5 [1.6] vs 7.3 [1.6] %, p = 0.024) and lower BMI (28.7±4.0 vs 33.2±4.7 kg/m², p<0.001). The South Asian group exhibited significantly higher basal endogenous glucose production (19.1 [9.1] vs 14.4 [6.8] µmol/kgFFM⋅min, p = 0.003). There were no significant differences between the groups in total glucose disposal (39.1±20.4 vs 39.2±17.6 µmol/kgFFM⋅min, p = 0.99) or first phase insulin secretion (AUC_{0–8 min}: 220 [302] vs 124 [275] pM, p = 0.35). In South Asian subjects there was a tendency towards positive correlations between endogenous glucose production and resting and clamp energy expenditure.

Conclusions

Subjects of South Asian ethnicity with type 2 diabetes, despite being younger and leaner, had higher basal endogenous glucose production, indicating higher hepatic insulin resistance, and a trend towards higher use of carbohydrates as fasting energy substrate compared to Nordic subjects. These findings may contribute to the understanding of the observed differences in prevalence of type 2 diabetes between the ethnic groups.     

IOL Tilt and Decentration Estimation from 3 Dimensional Reconstruction of OCT Image

Purpose

To evaluate intraocular lens (IOL) tilt and decentration by anterior segment optical coherence tomography (AS-OCT) using 3-dimensional (3D) reconstruction method.

Design

Prospective observational case series.

Participants

Thirty-nine patients (39 eyes) were included.

Methods

The IOL positions of all eyes were examined by AS-OCT. Images were obtained in 4 axes (0–180 degrees, 45–225 degrees, 90–270 degrees, and 135–315 degrees) using the quadrant-scan model. The cross-sectional images were analyzed with MATLAB software.

Main Outcome Measures

The angle (θ) between the reference pupillary plane and the IOL plane, the distances between the center points of the pupil circle and the IOL on the x-axis (dx) and y-axis (dy) and the spatial distance (ds) were calculated after 3D-reconstruction.

Results

The mean angle (θ) between the pupillary plane and the IOL plane was 2.94±0.99 degrees. The mean IOL decentration of dx and dy was 0.32±0.26 mm and 0.40±0.27 mm, respectively. The ds of the IOL decentration was 0.56±0.31 mm. There was no significant correlation between the ocular residual astigmatism (ORA) and the tilted angle or the decentration distance. There was a significant correlation between the ORA and total astigmatism (r = 0.742, P<0.001). There was no significant correlation between the postoperative best corrected visual acuity (BCVA) and the ORA (r = 0.156; P = 0.344), total astigmatism (r = 0.012; P = 0.942), tilted angle (θ; r = 0.172; P = 0.295) or decentration distance (dx: r = 0.191, P = 0.244; dy: r = 0.253, P = 0.121; ds: r = 0.298, P = 0.065).

Conclusions

AS-OCT can be used as an alternative for the analysis of IOL tilt and decentration using 3D-reconstruction.     

Consistent Condom Use Increases the Colonization of Lactobacillus crispatus in the Vagina

Background

Non-hormonal contraception methods have been widely used, but their effects on colonization by vaginal lactobacilli remain unclear.

Objective

To determine the association between non-hormonal contraception methods and vaginal lactobacilli on women’s reproductive health.

Methods

The cross-sectional study included 164 healthy women between 18–45 years of age. The subjects were divided into different groups on the basis of the different non-hormonal contraception methods used by them. At the postmenstrual visit (day 21 or 22 of the menstrual cycle), vaginal swabs were collected for determination of Nugent score, quantitative culture and real-time polymerase chain reaction (PCR) of vaginal lactobacilli. The prevalence, colony counts and 16S rRNA gene expression of the Lactobacillus strains were compared between the different groups by Chi-square and ANOVA statistical analysis methods.

Results

A Nugent score of 0–3 was more common in the condom group (93.1%) than in the group that used an interuterine device(IUD) (75.4%), (p = 0.005). The prevalence of H₂O₂-producing Lactobacillus was significantly higher in the condom group (82.3%) than in the IUD group (68.2%), (p = 0.016). There was a significant difference in colony count (mean ± standard error (SE), log₁₀colony forming unit (CFU)/ml) of H₂O₂-producing Lactobacillus between condom users (7.81±0.14) and IUD users (6.54±0.14), (p = 0.000). The 16S rRNA gene expression (mean ± SE, log₁₀copies/ml) of Lactobacillus crispatus was significantly higher in the condom group (8.09±0.16) than in the IUD group (6.03±0.18), (p = 0.000).

Conclusion

Consistent condom use increases the colonization of Lactobacillus crispatus in the vagina and may protect against both bacterial vaginosis (BV) and human immunodeficiency virus (HIV).     

Measurement of Pulmonary Flow Reserve and Pulmonary Index of Microcirculatory Resistance for Detection of Pulmonary Microvascular Obstruction

Background

The pulmonary microcirculation is the chief regulatory site for resistance in the pulmonary circuit. Despite pulmonary microvascular dysfunction being implicated in the pathogenesis of several pulmonary vascular conditions, there are currently no techniques for the specific assessment of pulmonary microvascular integrity in humans. Peak hyperemic flow assessment using thermodilution-derived mean transit-time (T_mn) facilitate accurate coronary microcirculatory evaluation, but remain unvalidated in the lung circulation. Using a high primate model, we aimed to explore the use of T_mn as a surrogate of pulmonary blood flow for the purpose of measuring the novel indices Pulmonary Flow Reserve [PFR = (maximum hyperemic)/(basal flow)] and Pulmonary Index of Microcirculatory Resistance [PIMR = (maximum hyperemic distal pulmonary artery pressure)×(maximum hyperemic T_mn)]. Ultimately, we aimed to investigate the effect of progressive pulmonary microvascular obstruction on PFR and PIMR.

Methods and Results

Temperature- and pressure-sensor guidewires (TPSG) were placed in segmental pulmonary arteries (SPA) of 13 baboons and intravascular temperature measured. T_mn and hemodynamics were recorded at rest and following intra-SPA administration of the vasodilator agents adenosine (10–400 µg/kg/min) and papaverine (3–24 mg). Temperature did not vary with intra-SPA sensor position (0.010±0.009 v 0.010±0.009°C; distal v proximal; p = 0.1), supporting T_mn use in lung for the purpose of hemodynamic indices derivation. Adenosine (to 200 µg/kg/min) & papaverine (to 24 mg) induced dose-dependent flow augmentations (40±7% & 35±13% T_mn reductions v baseline, respectively; p<0.0001). PFR and PIMR were then calculated before and after progressive administration of ceramic microspheres into the SPA. Cumulative microsphere doses progressively reduced PFR (1.41±0.06, 1.26±0.19, 1.17±0.07 & 1.01±0.03; for 0, 10⁴, 10⁵ & 10⁶ microspheres; p = 0.009) and increased PIMR (5.7±0.6, 6.3±1.0, 6.8±0.6 & 7.6±0.6 mmHg.sec; p = 0.0048).

Conclusions

Thermodilution-derived mean transit time can be accurately and reproducibly measured in the pulmonary circulation using TPSG. Mean transit time-derived PFR and PIMR can be assessed using a TPSG and adenosine or papaverine as hyperemic agents. These novel indices detect progressive pulmonary microvascular obstruction and thus have with a potential role for pulmonary microcirculatory assessment in humans.     

Disease Resistance in Atlantic Salmon (Salmo salar): Coinfection of the Intracellular Bacterial Pathogen Piscirickettsia salmonis and the Sea Louse Caligus rogercresseyi

Background

Naturally occurring coinfections of pathogens have been reported in salmonids, but their consequences on disease resistance are unclear. We hypothesized that 1) coinfection of Caligus rogercresseyi reduces the resistance of Atlantic salmon to Piscirickettsia salmonis; and 2) coinfection resistance is a heritable trait that does not correlate with resistance to a single infection.

Methodology

In total, 1,634 pedigreed Atlantic salmon were exposed to a single infection (SI) of P. salmonis (primary pathogen) or coinfection with C. rogercresseyi (secondary pathogen). Low and high level of coinfection were evaluated (LC = 44 copepodites per fish; HC = 88 copepodites per fish). Survival and quantitative genetic analyses were performed to determine the resistance to the single infection and coinfections.

Main Findings

C. rogercresseyi significantly increased the mortality in fish infected with P. salmonis (SI mortality = 251/545; LC mortality = 544/544 and HC mortality = 545/545). Heritability estimates for resistance to P. salmonis were similar and of medium magnitude in all treatments (h ² _SI = 0.23±0.07; h ² _LC = 0.17±0.08; h ² _HC = 0.24±0.07). A large and significant genetic correlation with regard to resistance was observed between coinfection treatments (r_g LC-HC = 0.99±0.01) but not between the single and coinfection treatments (r_g SI-LC = −0.14±0.33; r_g SI-HC = 0.32±0.34).

Conclusions/Significance

C. rogercresseyi, as a secondary pathogen, reduces the resistance of Atlantic salmon to the pathogen P. salmonis. Resistance to coinfection of Piscirickettsia salmonis and Caligus rogercresseyi in Atlantic salmon is a heritable trait. The absence of a genetic correlation between resistance to a single infection and resistance to coinfection indicates that different genes control these processes. Coinfection of different pathogens and resistance to coinfection needs to be considered in future research on salmon farming, selective breeding and conservation.     

Meta-Analysis of Randomised Clinical Trials Comparing Idarubicin + Cytarabine with Daunorubicin + Cytarabine as the Induction Chemotherapy in Patients with Newly Diagnosed Acute Myeloid Leukaemia

Background

To determine whether the use of idarubicin+cytarabine (IA) is more effective than the use of daunorubicin+cytarabine (DA) as induction chemotherapy for patients with newly diagnosed acute myeloid leukaemia.

Methods

A computer-based search was performed. Randomised trials comparing IA with DA as induction therapy for newly diagnosed AML were included in this meta-analysis. The primary outcome of interest for our analysis was survival (disease-free survival, event-free survival and overall survival); the secondary endpoint was complete remission.

Results

Ten trials with 4,060 patients were eligible for this meta-analysis. Our pooled results suggest that IA is associated with a significant advantage in CR (RR = 1·23; 95% CI = 1·07–1·41, p = 0.004), EFS (HR = 0·64; 95% CI = 0·45–0·91, p = 0.013), and OS (HR = 0·88; 95% CI = 0·81–0·95, p = 0.02) but not in DFS (HR = 0·90; 95% CI = 0·80–1·00, p = 0.06). In the subgroup analysis, age had a significant interaction with OS and CR benefits.

Conclusion

Our analysis indicated that IA could improve the duration of overall survival compared to DA as induction therapy for young patients with newly diagnosed AML. Further study is needed to determine whether IA can produce clinical benefits in selected genetic or molecular subgroups of young AML patients.     

Pulmonary and Cardiac Function in Asymptomatic Obese Subjects and Changes following a Structured Weight Reduction Program: A Prospective Observational Study

Background

The prevalence of obesity is rising. Obesity can lead to cardiovascular and ventilatory complications through multiple mechanisms. Cardiac and pulmonary function in asymptomatic subjects and the effect of structured dietary programs on cardiac and pulmonary function is unclear.

Objective

To determine lung and cardiac function in asymptomatic obese adults and to evaluate whether weight loss positively affects functional parameters.

Methods

We prospectively evaluated bodyplethysmographic and echocardiographic data in asymptomatic subjects undergoing a structured one-year weight reduction program.

Results

74 subjects (32 male, 42 female; mean age 42±12 years) with an average BMI 42.5±7.9, body weight 123.7±24.9 kg were enrolled. Body weight correlated negatively with vital capacity (R = −0.42, p<0.001), FEV1 (R = −0.497, p<0.001) and positively with P 0.1 (R = 0.32, p = 0.02) and myocardial mass (R = 0.419, p = 0.002). After 4 months the study subjects had significantly reduced their body weight (−26.0±11.8 kg) and BMI (−8.9±3.8) associated with a significant improvement of lung function (absolute changes: vital capacity +5.5±7.5% pred., p<0.001; FEV1+9.8±8.3% pred., p<0.001, ITGV+16.4±16.0% pred., p<0.001, SR tot −17.4±41.5% pred., p<0.01). Moreover, P0.1/Pimax decreased to 47.7% (p<0.01) indicating a decreased respiratory load. The change of FEV1 correlated significantly with the change of body weight (R = −0.31, p = 0.03). Echocardiography demonstrated reduced myocardial wall thickness (−0.08±0.2 cm, p = 0.02) and improved left ventricular myocardial performance index (−0.16±0.35, p = 0.02). Mitral annular plane systolic excursion (+0.14, p = 0.03) and pulmonary outflow acceleration time (AT +26.65±41.3 ms, p = 0.001) increased.

Conclusion

Even in asymptomatic individuals obesity is associated with abnormalities in pulmonary and cardiac function and increased myocardial mass. All the abnormalities can be reversed by a weight reduction program.     

Amiodarone Inhibits Apamin-Sensitive Potassium Currents

Background

Apamin sensitive potassium current (I _KAS), carried by the type 2 small conductance Ca²⁺-activated potassium (SK2) channels, plays an important role in post-shock action potential duration (APD) shortening and recurrent spontaneous ventricular fibrillation (VF) in failing ventricles.

Objective

To test the hypothesis that amiodarone inhibits I _KAS in human embryonic kidney 293 (HEK-293) cells.

Methods

We used the patch-clamp technique to study I _KAS in HEK-293 cells transiently expressing human SK2 before and after amiodarone administration.

Results

Amiodarone inhibited I_KAS in a dose-dependent manner (IC₅₀, 2.67±0.25 µM with 1 µM intrapipette Ca²⁺). Maximal inhibition was observed with 50 µM amiodarone which inhibited 85.6±3.1% of I_KAS induced with 1 µM intrapipette Ca²⁺ (n = 3). I_KAS inhibition by amiodarone was not voltage-dependent, but was Ca²⁺-dependent: 30 µM amiodarone inhibited 81.5±1.9% of I _KAS induced with 1 µM Ca²⁺ (n = 4), and 16.4±4.9% with 250 nM Ca²⁺ (n = 5). Desethylamiodarone, a major metabolite of amiodarone, also exerts voltage-independent but Ca²⁺ dependent inhibition of I _KAS.

Conclusion

Both amiodarone and desethylamiodarone inhibit I _KAS at therapeutic concentrations. The inhibition is independent of time and voltage, but is dependent on the intracellular Ca²⁺ concentration. SK2 current inhibition may in part underlie amiodarone''s effects in preventing electrical storm in failing ventricles.     

Cross-Talk in Mechanomyographic Signals from the Forearm Muscles during Sub-Maximal to Maximal Isometric Grip Force

Purpose

This study aimed: i) to examine the relationship between the magnitude of cross-talk in mechanomyographic (MMG) signals generated by the extensor digitorum (ED), extensor carpi ulnaris (ECU), and flexor carpi ulnaris (FCU) muscles with the sub-maximal to maximal isometric grip force, and with the anthropometric parameters of the forearm, and ii) to quantify the distribution of the cross-talk in the MMG signal to determine if it appears due to the signal component of intramuscular pressure waves produced by the muscle fibers geometrical changes or due to the limb tremor.

Methods

Twenty, right-handed healthy men (mean ± SD: age  = 26.7±3.83 y; height  = 174.47±6.3 cm; mass  = 72.79±14.36 kg) performed isometric muscle actions in 20% increment from 20% to 100% of the maximum voluntary isometric contraction (MVIC). During each muscle action, MMG signals generated by each muscle were detected using three separate accelerometers. The peak cross-correlations were used to quantify the cross-talk between two muscles.

Results

The magnitude of cross-talk in the MMG signals among the muscle groups ranged from, R²_{x, y} = 2.45–62.28%. Linear regression analysis showed that the magnitude of cross-talk increased linearly (r² = 0.857–0.90) with the levels of grip force for all the muscle groups. The amount of cross-talk showed weak positive and negative correlations (r² = 0.016–0.216) with the circumference and length of the forearm respectively, between the muscles at 100% MVIC. The cross-talk values significantly differed among the MMG signals due to: limb tremor (MMG_TF), slow firing motor unit fibers (MMG_SF) and fast firing motor unit fibers (MMG_FF) between the muscles at 100% MVIC (p<0.05, η ² = 0.47–0.80).

Significance

The results of this study may be used to improve our understanding of the mechanics of the forearm muscles during different levels of the grip force.     

Direct Transformation of Lung Microenvironment by Interferon-α Treatment Counteracts Growth of Lung Metastasis of Hepatocellular Carcinoma

Background

Interferon (IFN)-α is effective in inhibiting tumor growth and metastasis of hepatocellular carcinoma (HCC). However, the biologic mechanisms of IFN-α treatment in lung metastasis are not yet clear.

Methods

The effect of IFN-α treatment was studied by using an orthotopic xenograft model and measuring tumor size and lung metastasis. Pretreatment with IFN-α before implantation of tumor was done to explore the effect of IFN-α on lung tissues. Cytokines and macrophages were measured by immunohistochemistry and/or PCR assay, using human origin or mouse origin primers to differentiate the sources. Circulating tumor cells (CTCs) were also assayed by flow cytometry.

Results

IFN-α treatment did not decrease the number of CTCs (0.075%±0.020% versus 0.063%±0.018%, P = 0.574, IFN-α–treated versus control groups), but did decrease the number and size of lung metastasis (number: 1.75±1.0 versus 28.0±6.3, P = 0.008; size [pixels]: 116.8±72.2 versus 5226.4±1355.7, P = 0.020), and inhibited macrophage infiltration (0.20%±0.04% versus 1.36%±0.21%, P = 0.0058) and alteration of matrix metalloproteinase (MMP)-9 expression (mean integrated optical density (IOD): 5.1±1.7 versus 21.9±0.4, P<0.000) in the lung, which was independent of the primary tumor.

Conclusion

IFN-α inhibited lung metastasis by directly modulating the lung microenvironment.     

Impaired Chemosensitivity of Mouse Dorsal Raphe Serotonergic Neurons Overexpressing Serotonin 1A (Htr1a) Receptors

Background

Serotonergic system participates in a wide range of physiological processes and behaviors, but its role is generally considered as modulatory and noncrucial, especially concerning life-sustaining functions. We recently created a transgenic mouse line in which a functional deficit in serotonin homeostasis due to excessive serotonin autoinhibition was produced by inducing serotonin 1A receptor (Htr1a) overexpression selectively in serotonergic neurons (Htr1a raphe-overexpressing or Htr1a^RO mice). Htr1a^RO mice exhibit episodes of autonomic dysregulation, cardiovascular crises and death, resembling those of sudden infant death syndrome (SIDS) and revealing a life-supporting role of serotonergic system in autonomic control. Since midbrain serotonergic neurons are chemosensitive and are implicated in arousal we hypothesized that their chemosensitivity might be impaired in Htr1a^RO mice.

Principal findings

Loose-seal cell-attached recordings in brainstem slices revealed that serotonergic neurons in dorsal raphe nucleus of Htr1a^RO mice have dramatically reduced responses to hypercapnic challenge as compared with control littermates. In control mice, application of 9% CO₂ produced an increase in firing rate of serotonergic neurons (0.260±0.041 Hz, n = 20, p = 0.0001) and application of 3% CO₂ decreased their firing rate (−0.142±0.025 Hz, n = 17, p = 0.0008). In contrast, in Htr1a^RO mice, firing rate of serotonergic neurons was not significantly changed by 9% CO₂ (0.021±0.034 Hz, n = 16, p = 0.49) and by 3% CO₂ (0.012±0.046 Hz, n = 12, p = 0.97).

Conclusions

Our findings support the hypothesis that chemosensitivity of midbrain serotonergic neurons provides a physiological mechanism for arousal responses to life-threatening episodes of hypercapnia and that functional impairment, such as excessive autoinhibition, of midbrain serotonergic neuron responses to hypercapnia may contribute to sudden death.     

The Vitamin D Status in Inflammatory Bowel Disease

Context

There is no consensus on the vitamin D status of children and adolescents with inflammatory bowel disease (IBD).

Aim

To determine the vitamin D status of patients with IBD by comparing their serum 25(OH)D concentration to that of healthy controls.

Hypothesis

Serum 25(OH)D concentration will be lower in patients with IBD compared to controls.

Subjects and Methods

A case-controlled retrospective study of subjects with IBD (n = 58) of 2–20 years (male n = 31, age 16.38±2.21 years; female n = 27, age16.56±2.08 years) and healthy controls (n = 116; male n = 49, age 13.90±4.59 years; female n = 67, age 15.04±4.12years). Study subject inclusion criteria: diagnosis of Crohn’s disease (CD) or ulcerative colitis (UC). Vitamin D deficiency was defined as 25(OH)D of (<20 ng/mL) (<50 nmol/L), overweight as BMI of ≥85^th but <95^th percentile, and obesity as BMI ≥95^th percentile. Data were expressed as mean ± SD.

Results

Patients with CD, UC, and their controls had mean serum 25(OH)D concentrations of 61.69±24.43 nmol/L, 53.26±25.51, and 65.32±27.97 respectively (ANOVA, p = 0.196). The overweight/obese controls had significantly lower 25(OH)D concentration compared to the normal-weight controls (p = 0.031); whereas 25(OH)D concentration was similar between the normal-weight and overweight/obese IBD patients (p = 0.883). There was no difference in 25(OH)D between patients with UC and CD, or between subjects with active IBD and controls. However, IBD subjects with elevated ESR had significantly lower 25(OH)D than IBD subjects with normal ESR (p = 0.025), as well as controls (65.3±28.0 nmol/L vs. 49.5±25.23, p = 0.045).

Conclusion

There is no difference in mean serum 25(OH)D concentration between children and adolescents with IBD and controls. However, IBD subjects with elevated ESR have significantly lower 25(OH)D than controls. Therefore, IBD subjects with elevated ESR should be monitored for vitamin D deficiency.     

Spatial Characterization of Electrogram Morphology from Transmural Recordings in the Intact Normal Heart

Purpose

Unipolar (UE) and bipolar electrograms (BE) are utilized to identify arrhythmogenic substrate. We quantified the effect of increasing distance from the source of propagation on local electrogram amplitude; and determined if transmural electrophysiological gradients exist with respect to propagation and stimulation depth.

Methods

Mapping was performed on 5 sheep. Deployment of >50 quadripolar transmural needles in the LV were located in Cartesian space using Ensite. Contact electrograms from all needles were recorded during multisite bipolar pacing from epicardial then endocardial electrodes. Analysis was performed to determine stimulus distance to local activation time, peak negative amplitude (V_-P), and peak-peak amplitude (V_P-P) for (1) unfiltered UE, and (2) unfiltered and 30 Hz high-pass filtered BEs. Each sheep was analysed using repeated ANOVA.

Results

Increasing distance from the pacing sites led to significant (p<0.01) attenuation of UEs (V_-P = 7.0±0.5%; V_P-P = 5.4±0.3% per cm). Attenuation of BE with distance was insignificant (V_p-p unfiltered  = 2.2±0.5%; filtered  = 1.7±1.4% per cm). Independent of pacing depth, significant (p<0.01) transmural electrophysiological gradients were observed, with highest amplitude occurring at epicardial layers for UE and endocardial layers for BE. Furthermore, during pacing, propagation was earlier at the epicardium than endocardial layer by 1.6±2.0 ms (UE) and 1.4±2.8 ms (BE) (all p>0.01) during endocardial stimulation, and 2.3±2.4 ms (UE) and 1.8±3.7 ms (BE) during epicardal stimulation (all p<0.01).

Conclusions

Electrogram amplitude is inversely proportional to propagation distance for unipolar modalities only, which affected V_-P>V_P-P. Conduction propagates preferentially via the epicardium during stimulation and is believed to contribute to a transmural amplitude gradient.     

Association between Body Water Status and Acute Mountain Sickness

Purpose

The present study determined the association between body fluid variation and the development of acute mountain sickness (AMS) in adults.

Methods

Forty-three healthy participants (26 males and 17 females, age: 26±6 yr, height: 174±9 cm, weight: 68±12 kg) were passively exposed at a FiO₂ of 12.6% (simulated altitude hypoxia of 4500 m, PiO₂ = 83.9 mmHg) for 12-h. AMS severity was assessed using the Lake Louise Score (LLS). Food and drink intakes were consumed ad libitum and measured; all urine was collected. Before and after the 12-h exposure, body weight and plasma osmolality were measured and whole-body bioimpedance analysis was performed.

Results

The overall AMS incidence was 43% (38% males, 50% females). Participants who developed AMS showed lower fluid losses (3.0±0.9 vs. 4.5±2.0 ml/kg/h, p = 0.002), a higher fluid retention (1.9±1.5 vs. 0.6±0.8 ml/kg/h, p = 0.022), greater plasma osmolality decreases (−7±7 vs. −2±5 mOsm/kg, p = 0.028) and a larger plasma volume expansion (11±10 vs. 1±15%, p = 0.041) compared to participants not developing AMS. Net water balance (fluid intake – fluid loss) and the amount of fluid loss were strong predictors whether getting sick or not (Nagelkerkes r² = 0.532). The LLS score was related to net water balance (r = 0.358, p = 0.018), changes in plasma osmolality (r = −0.325, p = 0.033) and sodium concentration (r = −0.305, p = 0.047). Changes in the impedance vector length were related to weight changes (r = −0.550, p<0.001), fluid intake (r = −0.533, p<0.001) and net water balance (r = −0.590, p<0.001).

Conclusions

Participants developing AMS within 12 hours showed a positive net water balance due to low fluid loss. Thus measures to avoid excess fluid retention are likely to reduce AMS symptoms.     

Linkage between Increased Nociception and Olfaction via a SCN9A Haplotype

Background and Aims

Mutations reducing the function of Na_v1.7 sodium channels entail diminished pain perception and olfactory acuity, suggesting a link between nociception and olfaction at ion channel level. We hypothesized that if such link exists, it should work in both directions and gain-of-function Na_v1.7 mutations known to be associated with increased pain perception should also increase olfactory acuity.

Methods

SCN9A variants were assessed known to enhance pain perception and found more frequently in the average population. Specifically, carriers of SCN9A variants rs41268673C>A (P610T; n = 14) or rs6746030C>T (R1150W; n = 21) were compared with non-carriers (n = 40). Olfactory function was quantified by assessing odor threshold, odor discrimination and odor identification using an established olfactory test. Nociception was assessed by measuring pain thresholds to experimental nociceptive stimuli (punctate and blunt mechanical pressure, heat and electrical stimuli).

Results

The number of carried alleles of the non-mutated SCN9A haplotype rs41268673C/rs6746030C was significantly associated with the comparatively highest olfactory threshold (0 alleles: threshold at phenylethylethanol dilution step 12 of 16 (n = 1), 1 allele: 10.6±2.6 (n = 34), 2 alleles: 9.5±2.1 (n = 40)). The same SCN9A haplotype determined the pain threshold to blunt pressure stimuli (0 alleles: 21.1 N/m², 1 allele: 29.8±10.4 N/m², 2 alleles: 33.5±10.2 N/m²).

Conclusions

The findings established a working link between nociception and olfaction via Na_v1.7 in the gain-of-function direction. Hence, together with the known reduced olfaction and pain in loss-of-function mutations, a bidirectional genetic functional association between nociception and olfaction exists at Na_v1.7 level.     

Mayaro Virus Infection in Amazonia: A Multimodel Inference Approach to Risk Factor Assessment

Background

Arboviral diseases are major global public health threats. Yet, our understanding of infection risk factors is, with a few exceptions, considerably limited. A crucial shortcoming is the widespread use of analytical methods generally not suited for observational data – particularly null hypothesis-testing (NHT) and step-wise regression (SWR). Using Mayaro virus (MAYV) as a case study, here we compare information theory-based multimodel inference (MMI) with conventional analyses for arboviral infection risk factor assessment.

Methodology/Principal Findings

A cross-sectional survey of anti-MAYV antibodies revealed 44% prevalence (n = 270 subjects) in a central Amazon rural settlement. NHT suggested that residents of village-like household clusters and those using closed toilet/latrines were at higher risk, while living in non-village-like areas, using bednets, and owning fowl, pigs or dogs were protective. The “minimum adequate” SWR model retained only residence area and bednet use. Using MMI, we identified relevant covariates, quantified their relative importance, and estimated effect-sizes (β±SE) on which to base inference. Residence area (β _Village = 2.93±0.41; β _Upland = −0.56±0.33, β _Riverbanks = −2.37±0.55) and bednet use (β = −0.95±0.28) were the most important factors, followed by crop-plot ownership (β = 0.39±0.22) and regular use of a closed toilet/latrine (β = 0.19±0.13); domestic animals had insignificant protective effects and were relatively unimportant. The SWR model ranked fifth among the 128 models in the final MMI set.

Conclusions/Significance

Our analyses illustrate how MMI can enhance inference on infection risk factors when compared with NHT or SWR. MMI indicates that forest crop-plot workers are likely exposed to typical MAYV cycles maintained by diurnal, forest dwelling vectors; however, MAYV might also be circulating in nocturnal, domestic-peridomestic cycles in village-like areas. This suggests either a vector shift (synanthropic mosquitoes vectoring MAYV) or a habitat/habits shift (classical MAYV vectors adapting to densely populated landscapes and nocturnal biting); any such ecological/adaptive novelty could increase the likelihood of MAYV emergence in Amazonia.     

Longitudinal,Lateral and Transverse Axes of Forearm Muscles Influence the Crosstalk in the Mechanomyographic Signals during Isometric Wrist Postures

Problem Statement

In mechanomyography (MMG), crosstalk refers to the contamination of the signal from the muscle of interest by the signal from another muscle or muscle group that is in close proximity.

Purpose

The aim of the present study was two-fold: i) to quantify the level of crosstalk in the mechanomyographic (MMG) signals from the longitudinal (L_o), lateral (L_a) and transverse (T_r) axes of the extensor digitorum (ED), extensor carpi ulnaris (ECU) and flexor carpi ulnaris (FCU) muscles during isometric wrist flexion (WF) and extension (WE), radial (RD) and ulnar (UD) deviations; and ii) to analyze whether the three-directional MMG signals influence the level of crosstalk between the muscle groups during these wrist postures.

Methods

Twenty, healthy right-handed men (mean ± SD: age = 26.7±3.83 y; height = 174.47±6.3 cm; mass = 72.79±14.36 kg) participated in this study. During each wrist posture, the MMG signals propagated through the axes of the muscles were detected using three separate tri-axial accelerometers. The x-axis, y-axis, and z-axis of the sensor were placed in the L_o, L_a, and T_r directions with respect to muscle fibers. The peak cross-correlations were used to quantify the proportion of crosstalk between the different muscle groups.

Results

The average level of crosstalk in the MMG signals generated by the muscle groups ranged from: 34.28–69.69% for the L_o axis, 27.32–52.55% for the L_a axis and 11.38–25.55% for the T_r axis for all participants and their wrist postures. The T_r axes between the muscle groups showed significantly smaller crosstalk values for all wrist postures [F (2, 38) = 14–63, p<0.05, η ² = 0.416–0.769].

Significance

The results may be applied in the field of human movement research, especially for the examination of muscle mechanics during various types of the wrist postures.