Prophylactic inhibition of soluble epoxide hydrolase delays onset of nephritis and ameliorates kidney damage in NZB/W F1 mice

Epoxy-fatty-acids (EpFAs), cytochrome P450 dependent arachidonic acid derivatives, have been suggested to have anti-inflammatory properties, though their effects on autoimmune diseases like systemic lupus erythematosus (SLE) have yet to be investigated. We assessed the influence of EpFAs and their metabolites in lupus prone NZB/W F1 mice by pharmacological inhibition of soluble epoxide hydrolase (sEH, EPHX2). The sEH inhibitor 1770 was administered to lupus prone NZB/W F1 mice in a prophylactic and a therapeutic setting. Prophylactic inhibition of sEH significantly improved survival and reduced proteinuria. By contrast, sEH inhibitor-treated nephritic mice had no survival benefit; however, histological changes were reduced when compared to controls. In humans, urinary EpFA levels were significantly different in 47 SLE patients when compared to 10 healthy controls. Gene expression of EPHX2 was significantly reduced in the kidneys of both NZB/W F1 mice and lupus nephritis (LN) patients. Correlation of EpFAs with SLE disease activity and reduced renal EPHX gene expression in LN suggest roles for these components in human disease

Development and characterization of 16 microsatellite markers for the Louisiana pine snake, Pituophis ruthveni, and two congeners of conservation concern

We isolated and characterized 16 microsatellite loci from the Louisiana pine snake, Pituophis ruthveni. Loci were screened in 24 individuals from locations throughout its distribution in Louisiana and Texas. The number of alleles per locus ranged from 4 to 12, observed heterozygosity ranged from 0.200 to 0.875, and the probability of identity ranged from 0.043 to 0.298. We examined cross-species amplification at these loci in P. catenifer (bullsnakes and gopher snakes) and P. melanoleucus (pine snakes). These new markers provide tools for examining the conservation genetics of this species complex. Louisiana pine snakes face numerous threats: population densities are extremely low and their natural habitat has been severely altered and fragmented. In southern Canada, P. catenifer is at the northern extreme of its range and limited by the availability of suitable over-wintering sites. Hence, for these two species reduction of heterozygosity, potential for inbreeding, and increased effects of genetic drift are all of considerable conservation concern

Thermally stable gold(III) alkene and alkyne complexes: Synthesis, structures, and assessment of the trans‐influence on gold‐ligand bond enthalpies

The reaction of [C^C)Au(OEt2)2]+ with 1,5‐cyclooctadiene or norbornadiene affords the corresponding olefin complexes [(C^C)Au(COD)]SbF6 and [(C^C)Au(NBD)]SbF6, which are thermally stable in solution and the solid state (C^C = 4,4′‐di‐t‐butylbiphenyl‐2,2′‐diyl). The crystal structures of these complexes have been determined. By contrast, dienones such as dibenzylideneacetone are O‐ rather than C=C‐bonded. The reactions of (C^C)Au(OAcF)(L) (L = PMe3 or CNxyl) with B(C6F5)3 in the presence of bis(1‐adamantyl)acetylene give the mixed‐ligand alkyne complexes [(C^C)Au(AdC≡CAd)(L)]+, the first complexes of their type in gold chemistry. In the presence of an excess of acetylene these compounds are thermally stable in solution and as solids. The bonding of n‐ and π‐donor ligands to Au(III) fragments and the effect of the trans influence exerted by N‐ and C‐donors was explored with the aid of DFT calculations. Results show that the Au‐L bond enthalpies trans to anionic C are 35 ‐ 60% of the enthalpies trans to N, with strong π‐acceptors being particularly affected. In comparison with [Me2Au]+, the [(C^C)Au]+ fragment is more polar and in bond enthalpy terms resembles Me2Pt

Seton drainage prior to transanal advancement flap repair: useful or not?

Introduction: Transanal advancement flap repair (TAFR) provides a useful tool in the treatment of high transsphincteric fistulas. Recent studies indicate that TAFR fails in one out of three patients. Until now, no definite predictive factor for failure has been identified. Although some authors have reported that preoperative seton drainage might improve the outcome of TAFR, this could not be confirmed by others. We conducted the present study to assess the influence of preoperative seton drainage on the outcome of TAFR in a relatively large series. Methods: Between December 1992 and June 2008, a consecutive series of 278 patients [M/F = 179:99, median age 46 years (range, 19-73 years)] with cryptoglandular, transsphincteric fistula, passing through the upper or middle third of the external anal sphincter underwent TAFR. Patients were recruited from the colorectal units of two university hospitals (Erasmus Medical Center, Rotterdam, n = 211; and Leiden University Medical Center, Leiden, n = 67). Baseline characteristics did not differ between the two clinics. Sixty-eight of these patients underwent preoperative seton drainage for at least 2 months and until the day of the flap repair. Results: Median healing time was 2.2 months. In patients without preoperative seton drainage, the healing rate was 63%, whereas the healing rate was 67% in patients who underwent preoperative seton drainage. This difference was not statistically significant. No differences in healing rates were found between the series from Leiden and Rotterdam. Conclusion: Preoperative seton drainage does not improve the outcome of TAFR

the impact of uterine immaturity on obstetrical syndromes during adolescence

Pregnant nulliparous adolescents are at increased risk, inversely proportional to their age, of major obstetric syndromes, including preeclampsia, fetal growth restriction, and preterm birth. Emerging evidence indicates that biological immaturity of the uterus accounts for the increased incidence of obstetrical disorders in very young mothers, possibly compounded by sociodemographic factors associated with teenage pregnancy. The endometrium in most newborns is intrinsically resistant to progesterone signaling, and the rate of transition to a fully responsive tissue likely determines pregnancy outcome during adolescence. In addition to ontogenetic progesterone resistance, other factors appear important for the transition of the immature uterus to a functional organ, including estrogen-dependent growth and tissue-specific conditioning of uterine natural killer cells, which plays a critical role in vascular adaptation during pregnancy. The perivascular space around the spiral arteries is rich in endometrial mesenchymal stem-like cells, and dynamic changes in this niche are essential to accommodate endovascular trophoblast invasion and deep placentation. Here we evaluate the intrinsic (uterine-specific) mechanisms that predispose adolescent mothers to the great obstetrical syndromes and discuss the convergence of extrinsic risk factors that may be amenable to intervention

Near-surface hydraulic conductivity of Northern Hemisphere glaciers

The hydrology of near‐surface glacier ice remains a neglected aspect of glacier hydrology despite its role in modulating meltwater delivery to downstream environments. To elucidate the hydrological characteristics of this near‐surface glacial weathering crust, we describe the design and operation of a capacitance‐based piezometer that enables rapid, economical deployment across multiple sites and provides an accurate, high‐resolution record of near‐surface water‐level fluctuations. Piezometers were employed at 10 northern hemisphere glaciers, and through the application of standard bail–recharge techniques, we derive hydraulic conductivity (K) values from 0.003 to 3.519 m day−1, with a mean of 0.185 ± 0.019 m day−1. These results are comparable to those obtained in other discrete studies of glacier near‐surface ice, and for firn, and indicate that the weathering crust represents a hydrologically inefficient aquifer. Hydraulic conductivity correlated positively with water table height but negatively with altitude and cumulative short‐wave radiation since the last synoptic period of either negative air temperatures or turbulent energy flux dominance. The large range of K observed suggests complex interactions between meteorological influences and differences arising from variability in ice structure and crystallography. Our data demonstrate a greater complexity of near‐surface ice hydrology than hitherto appreciated and support the notion that the weathering crust can regulate the supraglacial discharge response to melt production. The conductivities reported here, coupled with typical supraglacial channel spacing, suggest that meltwater can be retained within the weathering crust for at least several days. Not only does this have implications for the accuracy of predictive meltwater run‐off models, but we also argue for biogeochemical processes and transfers that are strongly conditioned by water residence time and the efficacy of the cascade of sediments, impurities, microbes, and nutrients to downstream ecosystems. Because continued atmospheric warming will incur rising snowline elevations and glacier thinning, the supraglacial hydrological system may assume greater importance in many mountainous regions, and consequently, detailing weathering crust hydraulics represents a research priority because the flow path it represents remains poorly constrained

Electrically evoked compound action potentials are different depending on the site of cochlear stimulation.

One of the many parameters that can affect cochlear implant (CI) users' performance is the site of presentation of electrical stimulation, from the CI, to the auditory nerve. Evoked compound action potential (ECAP) measurements are commonly used to verify nerve function by stimulating one electrode contact in the cochlea and recording the resulting action potentials on the other contacts of the electrode array. The present study aimed to determine if the ECAP amplitude differs between the apical, middle, and basal region of the cochlea, if double peak potentials were more likely in the apex than the basal region of the cochlea, and if there were differences in the ECAP threshold and recovery function across the cochlea. ECAP measurements were performed in the apical, middle, and basal region of the cochlea at fixed sites of stimulation with varying recording electrodes. One hundred and forty one adult subjects with severe to profound sensorineural hearing loss fitted with a Standard or FLEX(SOFT) electrode were included in this study. ECAP responses were captured using MAESTRO System Software (MED-EL). The ECAP amplitude, threshold, and slope were determined using amplitude growth sequences. The 50% recovery rate was assessed using independent single sequences that have two stimulation pulses (a masker and a probe pulse) separated by a variable inter-pulse interval. For all recordings, ECAP peaks were annotated semi-automatically. ECAP amplitudes were greater upon stimulation of the apical region compared to the basal region of the cochlea. ECAP slopes were steeper in the apical region compared to the basal region of the cochlea and ECAP thresholds were lower in the middle region compared to the basal region of the cochlea. The incidence of double peaks was greater upon stimulation of the apical region compared to the basal region of the cochlea. This data indicates that the site and intensity of cochlear stimulation affect ECAP properties

Electrically evoked compound action potentials are different depending on the site of cochlear stimulation

One of the many parameters that can affect cochlear implant (CI) users' performance is the site of presentation of electrical stimulation, from the CI, to the auditory nerve. Evoked compound action potential (ECAP) measurements are commonly used to verify nerve function by stimulating one electrode contact in the cochlea and recording the resulting action potentials on the other contacts of the electrode array. The present study aimed to determine if the ECAP amplitude differs between the apical, middle, and basal region of the cochlea, if double peak potentials were more likely in the apex than the basal region of the cochlea, and if there were differences in the ECAP threshold and recovery function across the cochlea. ECAP measurements were performed in the apical, middle, and basal region of the cochlea at fixed sites of stimulation with varying recording electrodes. One hundred and forty one adult subjects with severe to profound sensorineural hearing loss fitted with a Standard or FLEX(SOFT) electrode were included in this study. ECAP responses were captured using MAESTRO System Software (MED-EL). The ECAP amplitude, threshold, and slope were determined using amplitude growth sequences. The 50% recovery rate was assessed using independent single sequences that have two stimulation pulses (a masker and a probe pulse) separated by a variable inter-pulse interval. For all recordings, ECAP peaks were annotated semi-automatically. ECAP amplitudes were greater upon stimulation of the apical region compared to the basal region of the cochlea. ECAP slopes were steeper in the apical region compared to the basal region of the cochlea and ECAP thresholds were lower in the middle region compared to the basal region of the cochlea. The incidence of double peaks was greater upon stimulation of the apical region compared to the basal region of the cochlea. This data indicates that the site and intensity of cochlear stimulation affect ECAP properties

Postnatal depression is associated with detrimental life-long and multi-generational impacts on relationship quality

Postnatal depression (PND) is known to be associated with a range of detrimental child and adolescent outcomes, resulting from its disruptive impact on mother-child relationship quality. However, until now little has been known about the impact of PND on the longer-term relationships between mothers and their children, and any intergenerational effects this may have. Mother-child relationship quality is of interest from an evolutionary perspective as it plays a role in the accrual of offspring embodied capital, thus affecting offspring quality and offspring’s capacity to subsequently invest in their own children. Relationships with offspring also mediate grandparent-grandchild relations; if PND negatively affects long-term mother–offspring relationship quality, it is also likely to negatively affect grandmaternal investment via reduced grandmother–grandchild relationship quality. Here, we use responses to a retrospective questionnaire study of postmenopausal women, largely from the UK and US, to assess the impact of PND occurring in generation 1 on mother–child relationship quality across the life course of the child (generation 2) with whom it was associated, and also on the relationship quality with grandchildren (generation 3) from that child. Average mother-child relationship quality was lower when the child’s birth was associated with PND. Multi-level regression modelling found that mother-child relationship quality decreased as PND symptom severity increased after controlling for individual effects and a variety of other factors known to influence relationship quality (individual mothers n = 296, mother-child dyads n = 646). Additionally, intergenerational relationships appear to be affected, with PND negatively associated with grandmother-grandchild relations (individual grandmothers n = 125, relations with grandchildren from n = 197 grandmother-parent dyads). That PND has long-term detrimental consequences for mother-child relationships, well beyond adolescence, highlights the need for investment in strategies to prevent PND and its cascade of negative multigenerational effects