Role of temperature in de-mixing absorbance spectra composed of compound electrolyte solutions.

This work is focused on the role of temperature in the de-mixing of absorbance spectra measured in mixed aqueous Na2SO4 and NaNO3 solutions. First, the influence of temperature on the absorbance spectrum of demineralized water was determined. Second, the absorbance spectra of five separate electrolytes (NaNO2, NaNO3, CaCl2, K2CO3, and NaOH) at three temperatures (4°C, 25°C, and 50°C) for concentrations ranging from 0.0625 M to 0.5 M were examined. These five electrolytes show similar temperature dependencies. Finally, absorbance spectra of mixed solutions were investigated at temperatures of 5°C, 15°C, 25°C, 35°C, and 45°C for concentrations ranging from 0.0625 M to 0.5 M per electrolyte in the mixture. The spectral window from 650 to 1100 nm was utilized to observe the ionic and temperature influences on the vibrational modes of the OH bond in the solvent molecules. The effects of dissolving Na2SO4 and NaNO3 are nonlinearly cumulative at lower temperatures indicating extended alteration of the water structure beyond the first hydration shell. A similar trend was observed for a mixture of Na2CO3 and NaCl. Furthermore, it was found that higher temperatures are better for recovering the separate component absorption signatures of an electrolyte mixture. The near-infrared spectral regime is well suited for integrated sensing, and therefore these results can help in designing an integrated sensor to identify inorganic species in water.

Betablockers do not increase efficacy of band ligation in primary prophylaxis but they improve survival in secondary prophylaxis of variceal bleeding.

BACKGROUND: Endoscopic band ligation (EBL) is used for primary (PP) and secondary prophylaxis (SP) of variceal bleeding. Current guidelines recommend combined use of non-selective beta-blockers (NSBBs) and EBL for SP, while in PP either NSBB or EBL should be used. AIM: To assess (re-)bleeding rates and mortality in cirrhotic patients receiving EBL for PP or SP for variceal bleeding. METHODS: (Re-)bleeding rates and mortality were retrospectively assessed with and without concomitant NSBB therapy after first EBL in PP and SP. RESULTS: Seven hundred and sixty-six patients with oesophageal varices underwent EBL from 01/2005 to 06/2015. Among the 284 patients undergoing EBL for PP, n = 101 (35.6%) received EBL only, while n = 180 (63.4%) received EBL + NSBBs. In 482 patients on SP, n = 163 (33.8%) received EBL only, while n = 299 (62%) received EBL + NSBBs. In PP, concomitant NSBB therapy neither decreased bleeding rates (log-rank: P = 0.353) nor mortality (log-rank: P = 0.497) as compared to EBL alone. In SP, similar re-bleeding rates were documented in EBL + NSBB vs EBL alone (log-rank: P = 0.247). However, EBL + NSBB resulted in a significantly lower mortality rate (log-rank: P<0.001). A decreased risk of death with EBL + NSBB in SP (hazard ratio, HR: 0.50; P<0.001) but not of rebleeding, transplantation or further decompensation was confirmed by competing risk analysis. Overall NSBB intake reduced 6-months mortality (HR: 0.53, P = 0.008) in SP, which was most pronounced in patients without severe/refractory ascites (HR: 0.37; P = 0.001) but not observed in patients with severe/refractory ascites (HR: 0.80; P = 0.567). CONCLUSIONS: EBL alone seems sufficient for PP of variceal bleeding. In SP, the addition of NSBB to EBL was associated with an improved survival within the first 6 months after EBL.

Author Correction: Characterization of slow cycling corneal limbal epithelial cells identifies putative stem cell markers.

A correction to this article has been published and is linked from the HTML version of this paper. The error has been fixed in the paper.

GABA-from Inhibition to Cognition: Emerging Concepts.

Neural functioning and plasticity can be studied on different levels of organization and complexity ranging from the molecular and synaptic level to neural circuitry of whole brain networks. Across neuroscience different methods are being applied to better understand the role of various neurotransmitter systems in the evolution of perception and cognition. GABA is the main inhibitory neurotransmitter in the adult mammalian brain and, depending on the brain region, up to 25% of the total number of cortical neurons are GABAergic interneurons. At the one end of the spectrum, GABAergic neurons have been accurately described with regard to cell morphological, molecular, and electrophysiological properties; at the other end researchers try to link GABA concentrations in specific brain regions to human behavior using magnetic resonance spectroscopy. One of the main challenges of modern neuroscience currently is to integrate knowledge from highly specialized subfields at distinct biological scales into a coherent picture that bridges the gap between molecules and behavior. In the current review, recent findings from different fields of GABA research are summarized delineating a potential strategy to develop a more holistic picture of the function and role of GABA.

Characterization of slow cycling corneal limbal epithelial cells identifies putative stem cell markers.

In order to identify reliable markers of corneal epithelial stem cells, we employed an inducible transgenic "pulse-chase" murine model (K5Tta × TRE-H2BGFP) to localize, purify, and characterize slow cycling cells in the cornea. The retention of GFP labeling in slowly dividing cells allowed for localization of these cells to the corneal limbus and their subsequent purification by FACS. Transcriptome analysis from slow cycling cells identified differentially expressed genes when comparing to GFP- faster-dividing cells. RNA-Seq data from corneal epithelium were compared to epidermal hair follicle stem cell RNA-Seq to identify genes representing common putative stem cell markers or determinants, which included Sox9, Fzd7, Actn1, Anxa3 and Krt17. Overlapping retention of GFP and immunohistochemical expression of Krt15, ΔNp63, Sox9, Actn1, Fzd7 and Krt17 were observed in our transgenic model. Our analysis presents an array of novel genes as putative corneal stem cell markers.

Pre-operative risk factors associated with need for vasoepididymostomy at the time of vasectomy reversal.

The absence of sperm in the ejaculate after vasectomy reversal is commonly caused by failure to recognize and subsequently bypass epididymal or proximal vasal obstruction at the time of vasectomy reversal. If intra-operative proximal obstruction is suspected, vasoepididymostomy (VE) is recommended rather than vasovasostomy (VV). We sought to calculate the associated risk of needing VE, rather than VV with time from original vasectomy (obstructive interval) using a large cohort of vasectomy reversal patients. We reviewed the electronic and paper vasectomy reversal database by a single surgeon from 1978 through 2012. We performed univariate analysis to identify variables that predicted the need for VE rather than VV, and then combined only significant univariates into our multi-variable analysis. 2697 total men underwent vasectomy reversal, and 239 were repeat procedures. Of the 5296 individual testes operated on, 1029 were VE. Significant variables that predicted the need for VE on univariate analysis included: age, obstructive time interval, vasectomy reversal after previous VV (repeat vasectomy reversal), and year the procedure was performed. On multi-variable analysis significant risk factors for VE were age above 50 (OR 1.36), repeat vasectomy reversal (OR 5.78), and greater obstructive time interval (OR 1.56). For every 3 years since original vasectomy, the risk of needing VE increases by 56%. There is a linear relationship between obstructive interval and need for VE. Men undergoing repeat vasectomy reversal have five times greater risk of requiring VE and men greater than 50 years of age are also at higher risk. Using these pre-operative predictors is helpful in identifying patients who will benefit from referral to an experienced surgeon who can perform VE.

Differential control of temporal and spatial aspects of cockroach leg coordination.

Ensembles of neuronal networks and sensory pathways participate in controlling the kinematic and dynamic parameters of animal movement necessary to achieve motor coordination. Determining the relative contribution of proprioceptive feedback is essential for understanding how animals sustain stable, coordinated locomotion in complex natural environments. Here, we focus on the role of chordotonal organs (COs), proprioceptors found in insect legs, in the spatial and temporal regulation of walking. We compare gait parameters of intact cockroaches (Periplaneta americana) and sensory-impaired ones, injected with pymetrozine, a chemical previously shown to abolish CO function in locusts. We verify that afferent CO activity in pymetrozine-treated cockroaches is inhibited, and analyze the effect of this sensory deprivation on inter-leg coordination. We find significant changes in tarsi placement and leg path trajectories after pymetrozine treatment. Leg touchdown accuracy, measured from relative tarsi positions of adjacent legs, is reduced in treated animals. Interestingly, despite poorer spatial coordination in both stance and swing, temporal properties of the gait remain largely the same as in the intact preparations, apart from changes in ipsilateral phase differences between front and middle legs. These findings provide insights into the role of COs in insect gait control and establish pymetrozine as a useful tool for further studies of insect locomotion.

HLA-haploidentical blood or marrow transplantation with high-dose, post-transplantation cyclophosphamide.

In the past, partially HLA-mismatched related donor, or HLA-haploidentical, blood or marrow transplantation (haploBMT), for hematologic malignancies has been complicated by unacceptably high incidences of graft rejection or GvHD resulting from intense bi-directional alloreactivity. Administration of high doses of cyclophosphamide early after haploBMT selectively kills proliferating, alloreactive T cells while sparing non-alloreactive T cells responsible for immune reconstitution and resistance to infection. In the clinic, haploBMT with high-dose, post-transplantation cyclophosphamide is associated with acceptably low incidences of fatal graft rejection, GvHD and non-relapse mortality, and provides an acceptable treatment option for hematologic malignancies patients lacking suitably HLA-matched donors. HaploBMT with PTCy is now being investigated as a treatment of hemoglobinopathy and as a method for inducing tolerance to solid organs transplanted from the same donor. Ongoing and future clinical trials will establish the hierarchy of donor preference for hematologic malignancy patients lacking an HLA-matched sibling.

Sensory feedback in cockroach locomotion: current knowledge and open questions.

The American cockroach, Periplaneta americana, provides a successful model for the study of legged locomotion. Sensory regulation and the relative importance of sensory feedback vs. central control in animal locomotion are key aspects in our understanding of locomotive behavior. Here we introduce the cockroach model and describe the basic characteristics of the neural generation and control of walking and running in this insect. We further provide a brief overview of some recent studies, including mathematical modeling, which have contributed to our knowledge of sensory control in cockroach locomotion. We focus on two sensory mechanisms and sense organs, those providing information related to loading and unloading of the body and the legs, and leg-movement-related sensory receptors, and present evidence for the instrumental role of these sensory signals in inter-leg locomotion control. We conclude by identifying important open questions and indicate future perspectives.

[Novel oral anticoagulants in gastroenterology routine]. / Bedeutung der neuen oralen Antikoagulanzien in der Gastroenterologie.

Novel direct-acting oral anticoagulants (NOAC) represent an effective new familiy of drugs and an interesting alternative to optimise and simplify anticoagulation. Rates of bleeding complications by NOAC are comparabel to those of warfarin but a previously assumed increase in gastrointestinal bleeding complications was meanwhile confirmed. Therefore, indications and contraindications concerning the use of NOAC should be closely considered. The endoscopic approach of gastrointestinal bleeding is conform to the recommended management of gastrointestinal bleeding complications under conventional anticoagulants or inhibitors of platelet aggregation. There are no specific antidotes to the anticoagulant effects of NOAC in case of bleeding. The recommendation concerning elective endoscopic procedures with high risk of bleeding more or less reflects expert oppinion. There are no recommendations on the basis of randomised studies. However, because of the short plasmatic half-life time of NOAC, their utilisation seems to be well controllable even in cases of high risk endoscopic interventions. More evidence based data about the periinterventional use of NOAC in endoscopic routine, in cases of endoscopic interventions with high bleeding risk or bleeding complications, bridging and the possibility of specific antidots in case of bleeding would be desirable.

Successful transplantation of kidney allografts in sensitized rats after syngeneic hematopoietic stem cell transplantation and fludarabine.

Current methods to remove donor-specific HLA antibody (DSA) from sensitized patients remain imperfect. We tested novel approaches to desensitization using an animal model of allogeneic sensitization with skin grafts from dark agouti (DA) to Lewis rats. At the peak IgG alloantibody response we transplanted DA kidneys into nephrectomized Lewis recipients (n = 6) and all died within 10 days from antibody-mediated rejection (AMR). Allogeneic hematopoietic stem cell transplants (HSCT) from DA donors failed to engraft after lethal or sub-lethal irradiation. Sensitized rats given lethal irradiation plus syngeneic green fluorescent protein (GFP) + HSCT had repopulation of blood, spleen, thymus and lymph nodes by GFP+ cells. At 2 months after HSCT, serum DSA levels were reduced 60-70% and DSA (IgG) production in cultured splenocytes was also significantly decreased. However, there was only a modest improvement in graft survival from an average of 6.5 to 13.9 (n = 9) days. Adding seven daily doses of fludarabine to the preconditioning regimen resulted in long-term survival (>90 days) in 7 out of 10 rat kidney allografts. We conclude that syngeneic HSCT performed after preconditioning with irradiation and fludarabine can reduce DSA, prevent DSA rebound and AMR, enabling successful transplantation in animals with strong antibody reactivity to the donor MHC.

Umbilical venous catheter-induced hepatic hematoma in neonates.

Umbilical vessel catheterization is common practice for infants in the neonatal intensive care unit (NICU). Umbilical venous catheters (UVC) although very useful as a means of obtaining vascular access, do not come without risks. Here we will describe three separate cases of infants in the NICU who, during their course of treatment, were found to have hepatic masses attributed to UVC misplacement. Two of the cases presented incidentally and one presented acutely. We believe liver hematomas may be a more common complication of malpositioned UVCs than previously believed. An appreciation of the complications of malpositioned UVCs should alert clinicians to screen for potential complications and to ensure ideal line placement.

Neither insects nor wind: ambophily in dioecious Chamaedorea palms (Arecaceae).

Pollination of Neotropical dioecious trees is commonly related to generalist insects. Similar data for non-tree species with separated genders are inconclusive. Recent studies on pollination of dioecious Chamaedorea palms (Arecaceae) suggest that species are either insect- or wind-pollinated. However, the wide variety of inflorescence and floral attributes within the genus suggests mixed pollination mode involving entomophily and anemophily. To evaluate this hypothesis, we studied the pollination of Chamaedorea costaricana, C. macrospadix, C. pinnatifrons and C. tepejilote in two montane forests in Costa Rica. A complementary morphological analysis of floral traits was carried out to distinguish species groups within the genus according to their most probable pollination mechanism. We conducted pollinator exclusion experiments, field observations on visitors to pistillate and staminate inflorescences, and trapped airborne pollen. A cluster analysis using 18 floral traits selected for their association with wind and insect pollination syndromes was carried out using 52 Chamaedorea species. Exclusion experiments showed that both wind and insects, mostly thrips (Thysanoptera), pollinated the studied species. Thrips used staminate inflorescences as brood sites and pollinated pistillate flowers by deception. Insects caught on pistillate inflorescences transported pollen, while traps proved that pollen is wind-borne. Our empirical findings clearly suggest that pollination of dioecious Chamaedorea palms is likely to involve both insects and wind. A cluster analysis showed that the majority of studied species have a combination of floral traits that allow for both pollination modes. Our pollination experiments and morphological analysis both suggest that while some species may be completely entomophilous or anemophilous, ambophily might be a common condition within Chamaedorea. Our results propose a higher diversity of pollination mechanisms of Neotropical dioecious species than previously suggested.

Safety and pharmacokinetics of XOMA 3AB, a novel mixture of three monoclonal antibodies against botulinum toxin A.

Botulinum neurotoxin A is a category A bioterrorism agent. Current antitoxin therapies are scarce and produce adverse reactions. XOMA 3AB consists of 3 IgG1 monoclonal antibodies (MAbs), each with a distinct human or humanized variable region, which bind to distinct epitopes on botulinum neurotoxin serotype A. This first-in-human study evaluated the safety and pharmacokinetics (PK) of escalating doses of XOMA 3AB administered intravenously (i.v.) to healthy adults. In this double-blind placebo-controlled dose escalation study, 3 cohorts of 8 healthy subjects received a single intravenous dose of XOMA 3AB or placebo at a 3:1 ratio. Follow-up examinations included physical examinations, hematology and chemistry blood tests, electrocardiograms, and pharmacokinetics. Pharmacokinetic parameters were estimated using noncompartmental methods. There were no infusion discontinuations or hypersensitivity reactions. Two or more subjects experienced headache, hyperglycemia, or anemia; none was dose related. All adverse events (AEs) were mild to moderate except for an episode of exercise-induced elevation of a subject's creatine phosphokinase (CPK) level, unrelated to XOMA 3AB. Concentration-time plots demonstrated a peak in MAb concentrations 1 to 2 h after completion of the infusion, after which the levels declined in a biexponential decay pattern for all analytes. For each MAb, the maximum concentration of drug in serum (Cmax) and the area under the concentration-time curve from 0 to infinity (AUCinf) increased as the dose increased. Clearance of the humanized mouse MAb was more rapid than that of the two fully human MAbs, particularly at the lowest dose. None of the MAbs was immunogenic. At the doses administered, XOMA 3AB was well tolerated. These safety findings support further investigation of XOMA 3AB as a potential agent for botulism treatment and postexposure prophylaxis. (This study has been registered at ClinicalTrials.gov under registration no. NCT01357213.).

Epidermal Snail expression drives skin cancer initiation and progression through enhanced cytoprotection, epidermal stem/progenitor cell expansion and enhanced metastatic potential.

Expression of the EMT-inducing transcription factor Snail is enhanced in different human cancers. To investigate the in vivo role of Snail during progression of epithelial cancer, we used a mouse model with skin-specific overexpression of Snail. Snail transgenic mice spontaneously developed distinct histological subtypes of skin cancer, such as basal cell carcinoma, squamous cell carcinoma and sebaceous gland carcinoma. Development of sebaceous gland carcinomas strongly correlated with the direct and complete repression of Blimp-1, a central regulator of sebocyte homeostasis. Snail expression in keratinocyte stem cells significantly promotes their proliferation associated with an activated FoxM1 gene expression signature, resulting in a larger pool of Mts24-marked progenitor cells. Furthermore, primary keratinocytes expressing Snail showed increased survival and strong resistance to genotoxic stress. Snail expression in a skin-specific p53-null background resulted in accelerated formation of spontaneous tumours and enhanced metastasis. Our data demonstrate that in vivo expression of Snail results in de novo epithelial carcinogenesis by allowing enhanced survival, expansion of the cancer stem cell pool with accumulated DNA damage, a block in terminal differentiation and increased proliferation rates of tumour-initiating cells.

Stability of colistimethate sodium in aqueous solution.

Colistimethate sodium, increasingly used to treat multidrug-resistant Gram-negative infections, spontaneously hydrolyzes to form colistin A (polymyxin E1) and B (polymyxin E2/B) when mixed with water. High levels of these active breakdown products at the time of administration have been associated with nephrotoxicity and even death. In this study, reconstituted colistimethate sodium was shown to be stable (<1.0% colistin A/B formation) for up to 24 h when stored at 21, 0, -20, and -70°C.