Correlation between altered central pain processing and concentration of peritoneal fluid inflammatory cytokines in endometriosis patients with chronic pelvic pain

Translational research has not yet elucidated whether alterations in central pain processes are related to peripheral inflammatory processes in chronic pain patients. We tested the hypothesis that the concentration of cytokines in the peritoneal fluid of endometriosis patients with chronic pain correlate with parameters of hyperexcitability of the nociceptive system. The concentrations of 15 peritoneal fluid cytokines were measured in 11 patients with chronic pelvic pain and a diagnosis of endometriosis. Six parameters assessing central pain processes were recorded. Positive correlations between concentration of some cytokines in the peritoneal fluid and amplification of central pain processing were found. The results suggest that inflammatory mechanisms may be important in the pathophysiology of altered central pain processes and that cytokines produced in the environment of endometriosis could act as mediators between the peripheral lesion and changes in central nociceptive processes.

New online method for water isotope analysis of speleothem fluid inclusions using laser absorption spectroscopy (WS-CRDS)

A new online method to analyse water isotopes of speleothem fluid inclusions using a wavelength scanned cavity ring down spectroscopy (WS-CRDS) instrument is presented. This novel technique allows us simultaneously to measure hydrogen and oxygen isotopes for a released aliquot of water. To do so, we designed a new simple line that allows the online water extraction and isotope analysis of speleothem samples. The specificity of the method lies in the fact that fluid inclusions release is made on a standard water background, which mainly improves the δ D robustness. To saturate the line, a peristaltic pump continuously injects standard water into the line that is permanently heated to 140 °C and flushed with dry nitrogen gas. This permits instantaneous and complete vaporisation of the standard water, resulting in an artificial water background with well-known δ D and δ18O values. The speleothem sample is placed in a copper tube, attached to the line, and after system stabilisation it is crushed using a simple hydraulic device to liberate speleothem fluid inclusions water. The released water is carried by the nitrogen/standard water gas stream directly to a Picarro L1102-i for isotope determination. To test the accuracy and reproducibility of the line and to measure standard water during speleothem measurements, a syringe injection unit was added to the line. Peak evaluation is done similarly as in gas chromatography to obtain &delta D; and δ18O isotopic compositions of measured water aliquots. Precision is better than 1.5 ‰ for δ D and 0.4 ‰ for δ18O for water measurements for an extended range (−210 to 0 ‰ for δ D and −27 to 0 ‰ for δ18O) primarily dependent on the amount of water released from speleothem fluid inclusions and secondarily on the isotopic composition of the sample. The results show that WS-CRDS technology is suitable for speleothem fluid inclusion measurements and gives results that are comparable to the isotope ratio mass spectrometry (IRMS) technique.

Human 3β-hydroxysteroid dehydrogenase deficiency seems to affect fertility but may not harbor a tumor risk: lesson from an experiment of nature.

CONTEXT 3β-hydroxysteroid dehydrogenase deficiency (3βHSD) is a rare disorder of sexual development and steroidogenesis. There are two isozymes of 3βHSD, HSD3B1 and HSD3B2. Human mutations are known for the HSD3B2 gene which is expressed in the gonads and the adrenals. Little is known about testis histology, fertility and malignancy risk. OBJECTIVE To describe the molecular genetics, the steroid biochemistry, the (immuno-)histochemistry and the clinical implications of a loss-of-function HSD3B2 mutation. METHODS Biochemical, genetic and immunohistochemical investigations on human biomaterials. RESULTS A 46,XY boy presented at birth with severe undervirilization of the external genitalia. Steroid profiling showed low steroid production for mineralocorticoids, glucocorticoids and sex steroids with typical precursor metabolites for HSD3B2 deficiency. The genetic analysis of the HSD3B2 gene revealed a homozygous c.687del27 deletion. At pubertal age, he showed some virilization of the external genitalia and some sex steroid metabolites appeared likely through conversion of precursors secreted by the testis and converted by unaffected HSD3B1 in peripheral tissues. However, he also developed enlarged breasts through production of estrogens in the periphery. Testis histology in late puberty revealed primarily a Sertoli-cell-only pattern and only few tubules with arrested spermatogenesis, presence of few Leydig cells in stroma, but no neoplastic changes. CONCLUSIONS The testis with HSD3B2 deficiency due to the c.687del27 deletion does not express the defective protein. This patient is unlikely to be fertile and his risk for gonadal malignancy is low. Further studies are needed to obtain firm knowledge on malignancy risk for gonads harboring defects of androgen biosynthesis.

Norm enforcement in the city revisited: An international field experiment of altruistic punishment, norm maintenance, and broken windows

In laboratory experiments, people are willing to sanction norms at a cost—a behavioral tendency called altruistic punishment. However, the degree to which these findings can be generalized to real-world interactions is still debated. Only a small number of field experiments have been conducted, and initial results suggest that punishment is less frequent outside of the lab. This study replicates one of the first field experiments on altruistic punishment and builds ties to research on norm compliance and the broken windows theory. The original study addressed the enforcement of the anti-littering norm in Athens. We replicate this study in Bern, Zurich, and New York City. As an extension, we investigate how the experimental context (clean vs littered) impacts social norm enforcement. As a second extension, we investigate how opportunity structure impacts the maintenance of the anti-littering norm. Findings indicate that norms are universally enforced, although significantly less than in the standard laboratory experiment,and that enforcement is significantly more common in Switzerland than in New York. Moreover, individuals prefer more subtle forms of enforcement to direct punishment. We also find that enforcement is less frequent in littered than in clean contexts, suggesting that broken windows might not only foster deviant behavior but also weaken informal social control. Finally, we find that opportunity structure can encourage people to maintain norms, as indicated by the fact that people are more likely to voluntarily pick up litter when it is closer to a trash bin.

Statistical Methods for Differential Expressions of Genes Detected in Multiple-Condition Experiment of Microarray

Most studies of differential gene-expressions have been conducted between two given conditions. The two-condition experimental (TCE) approach is simple in that all genes detected display a common differential expression pattern responsive to a common two-condition difference. Therefore, the genes that are differentially expressed under the other conditions other than the given two conditions are undetectable with the TCE approach. In order to address the problem, we propose a new approach called multiple-condition experiment (MCE) without replication and develop corresponding statistical methods including inference of pairs of conditions for genes, new t-statistics, and a generalized multiple-testing method for any multiple-testing procedure via a control parameter C. We applied these statistical methods to analyze our real MCE data from breast cancer cell lines and found that 85 percent of gene-expression variations were caused by genotypic effects and genotype-ANAX1 overexpression interactions, which agrees well with our expected results. We also applied our methods to the adenoma dataset of Notterman et al. and identified 93 differentially expressed genes that could not be found in TCE. The MCE approach is a conceptual breakthrough in many aspects: (a) many conditions of interests can be conducted simultaneously; (b) study of association between differential expressions of genes and conditions becomes easy; (c) it can provide more precise information for molecular classification and diagnosis of tumors; (d) it can save lot of experimental resources and time for investigators.^

Seawater carbonate chemistry and net dissolution rate for experiment of Shiraho reef

Acidification of the oceans by increasing anthropogenic CO2 emissions will cause a decrease in biogenic calcification and an increase in carbonate dissolution. Previous studies have suggested that carbonate dissolution will occur in polar regions and in the deep sea where saturation state with respect to carbonate minerals (Omega) will be <1 by 2100. Recent reports demonstrate nocturnal carbonate dissolution of reefs, despite a Omega a (aragonite saturation state) value of >1. This is probably related to the dissolution of reef carbonate (Mg-calcite), which is more soluble than aragonite. However, the threshold of Omega for the dissolution of natural sediments has not been clearly determined. We designed an experimental dissolution system with conditions mimicking those of a natural coral reef, and measured the dissolution rates of aragonite in corals, and of Mg-calcite excreted by other marine organisms, under conditions of Omega a > 1, with controlled seawater pCO2. The experimental data show that dissolution of bulk carbonate sediments sampled from a coral reef occurs at Omega a values of 3.7 to 3.8. Mg-calcite derived from foraminifera and coralline algae dissolves at Omega a values between 3.0 and 3.2, and coralline aragonite starts to dissolve when Omega a = 1.0. We show that nocturnal carbonate dissolution of coral reefs occurs mainly by the dissolution of foraminiferans and coralline algae in reef sediments.

Growth, respiration and photophysiology of coral massive Porites spp. in the experiment of Moorea

I tested the hypothesis that high pCO2 (76.6 Pa and 87.2 Pa vs. 42.9 Pa) has no effect on the metabolism of juvenile massive Porites spp. after 11 days at 28 °C and 545 µmol quanta/m**2/s. The response was assessed as aerobic dark respiration, skeletal weight (i.e., calcification), biomass, and chlorophyll fluorescence. Corals were collected from the shallow (3-4 m) back reef of Moorea, French Polynesia (17°28.614'S, 149°48.917'W), and experiments conducted during April and May 2011. An increase in pCO2 to 76.6 Pa had no effect on any dependent variable, but 87.2 Pa pCO2 reduced area-normalized (but not biomass-normalized) respiration 36 %, as well as maximum photochemical efficiency (Fv/Fm) of open RCIIs and effective photochemical efficiency of RCIIs in actinic light (Delta F/F'm ); neither biomass, calcification, nor the energy expenditure coincident with calcification (J/g) was effected. These results do not support the hypothesis that high pCO2 reduces coral calcification through increased metabolic costs and, instead, suggest that high pCO2 causes metabolic depression and photochemical impairment similar to that associated with bleaching. Evidence of a pCO2 threshold between 76.6 and 87.2 Pa for inhibitory effects on respiration and photochemistry deserves further attention as it might signal the presence of unpredictable effects of rising pCO2.

Chemical and isotope composition of poor fluid from gas-hydrate samples of ODP Site 146-892

Although the presence of extensive gas hydrate on the Cascadia margin, offshore from the western U.S. and Canada, has been inferred from marine seismic records and pore water chemistry, solid gas hydrate has only been found at one location. At Ocean Drilling Program (ODP) Site 892, offshore from central Oregon, gas hydrate was recovered close to the sediment-water interface at 2-19 m below the seafloor (mbsf) at 670 m water depth. The gas hydrate occurs as elongated platy crystals or crystal aggregates, mostly disseminated irregularly, with higher concentrations occurring in discrete zones, thin layers, and/or veinlets parallel or oblique to the bedding. A 2- to 3-cm thick massive gas hydrate layer, parallel to bedding, was recovered at ~17 mbsf. Gas from a sample of this layer was composed of both CH4 and H2S. This sample is the first mixed-gas hydrate of CH4-H2S documented in ODP; it also contains ethane and minor amounts of CO2. Measured temperatures of the recovered core ranged from 2 to -1.8°C and are 6 to 8 degrees lower than in-situ temperatures. These temperature anomalies were caused by the partial dissociation of the CH4-H2S hydrate during recovery without a pressure core sampler. During this dissociation, toxic levels of H2S (delta34S, +27.4?) were released. The delta13C values of the CH4 in the gas hydrate, -64.5 to -67.5? (PDB), together with deltaD values of -197 to -199? (SMOW) indicate a primarily microbial source for the CH4. The delta18O value of the hydrate H2O is +2.9? (SMOW), comparable with the experimental fractionation factor for sea-ice. The unusual composition (CH4-H2S) and depth distribution (2-19 mbsf) of this gas hydrate indicate mixing between a methane-rich fluid with a pore fluid enriched in sulfide; at this site the former is advecting along an inclined fault into the active sulfate reduction zone. The facts that the CH4-H2S hydrate is primarily confined to the present day active sulfate reduction zone (2-19 mbsf), and that from here down to the BSR depth (19-68 mbsf) the gas hydrate inferred to exist is a >=99% CH4 hydrate, suggest that the mixing of CH4 and H2S is a geologically young process. Because the existence of a mixed CH4-H2S hydrate is indicative of moderate to intense advection of a methane-rich fluid into a near surface active sulfate reduction zone, tectonically active (faulted) margins with organic-rich sediments and moderate to high sedimentation rates are the most likely regions of occurrence. The extension of such a mixed hydrate below the sulfate reduction zone should reflect the time-span of methane advection into the sulfate reduction zone.

Calcification rate of massive Porites spp. and Porites rus in the experiment of Moorea

This study tested the hypothesis that the response of corals to temperature and pCO2 is consistent between taxa. Juvenile massive Porites spp. and branches of P. rus from the back reef of Moorea were incubated for 1 month under combinations of temperature (29.3 °C and 25.6 °C) and pCO2 (41.6 Pa and 81.5 Pa) at an irradiance of 599 µmol quanta/m/s. Using microcosms and CO2 gas mixing technology, treatments were created in a partly nested design (tanks) with two between-plot factors (temperature and pCO2), and one within-plot factor (taxon); calcification was used as a dependent variable. pCO2 and temperature independently affected calcification, but the response differed between taxa. Massive Porites spp. was largely unaffected by the treatments, but P. rus grew 50% faster at 29.3 °C compared with 25.6 °C, and 28% slower at 81.5 Pa vs. 41.6 Pa CO2. A compilation of studies placed the present results in a broader context and tested the hypothesis that calcification for individual coral genera is independent of pH, [HCO3]-, and [CO3]2-. Unlike recent reviews, this analysis was restricted to studies reporting calcification in units that could be converted to nmol CaCO3/cm**2/h. The compilation revealed a high degree of variation in calcification as a function of pH, [HCO3]-, and [CO3]2-, and supported three conclusions: (1) studies of the effects of ocean acidification on corals need to pay closer attention to reducing variance in experimental outcomes to achieve stronger synthetic capacity, (2) coral genera respond in dissimilar ways to pH, [HCO3]-, and [CO3]2-, and (3) calcification of massive Porites spp. is relatively resistant to short exposures of increased pCO2, similar to that expected within 100 y.