Is volumetric modulated arc therapy with constant dose rate a valid option in radiation therapy for head and neck cancer patients?

Background

Intensity-modulated radiotherapy (IMRT) improves dose distribution in head and neck (HN) radiation therapy. Volumetric-modulated arc therapy (VMAT), a new form of IMRT, delivers radiation in single or multiple arcs, varying dose rates (VDR-VMAT) and gantry speeds, has gained considerable attention. Constant dose rate VMAT (CDR-VMAT) associated with a fixed gantry speed does not require a dedicated linear accelerator like VDR-VMAT. The present study explored the feasibility, efficiency and delivery accuracy of CDR-VMAT, by comparing it with IMRT and VDR-VMAT in treatment planning for HN cancer.

Turonian–Santonian radiolarians and planktonic foraminifers of the Upper Cretaceous sequences between Trabzon and Giresun areas in the Eastern Pontides,NE Turkey

In the “Eastern Pontides” (NE Turkey), the intense volcanic activity accompanying carbonate-siliceous sedimentation during the Late Cretaceous period ensured the occurrence of thick volcano-sedimentary sequences. Seventy-one radiolarian species belonging to 26 genera were identified from five stratigraphic sections of the Upper Cretaceous sequences between Trabzon and Giresun areas in NE Turkey. These species were obtained from the lower Turonian–lower Coniacian strata of the Çe?meler Formation, the Coniacian–lower Santonian strata of the Elmal? Dere Formation and the upper Santonian strata of the Ça?layan Formation. Coniacian–Campanian fauna, consisting of planktonic foraminifera Hedbergella, Marginotruncana, Globotruncana, Whiteinella and biserial heterohelicids as well as radiolarians, was recovered from the red pelagic limestones of the Elmal? Dere Formation known as marker horizon.     

Novel sulfenamides and sulfonamides based on pyridazinone and pyridazine scaffolds as CB1 receptor ligand antagonists

A series of sulfenamide and sulfonamide derivatives was synthesized and evaluated for the affinity at CB₁ and CB₂ receptors. The N-bornyl-S-(5,6-di-p-tolylpyridazin-3-yl)-sulfenamide, compound 11, displayed good affinity and high selectivity for CB₁ receptors (K_i values of 44.6?nM for CB₁ receptors and >40?μM for CB₂ receptors, respectively). The N-isopinocampheyl-sulfenamide 12 and its sulfonamide analogue 22 showed similar selectivity for CB₁ receptors with K_i values of 75.5 and 73.2?nM, respectively. These novel compounds behave as antagonists/inverse agonists at CB₁ receptor in the [³⁵S]-GTPγS binding assays, and none showed adequate predictive blood–brain barrier permeation, exhibiting low estimated LD₅₀. However, testing compound 12 in a supraspinal analgesic test (hot-plate) revealed that it was as effective as the classic CB₁ receptor antagonist rimonabant, in reversing the analgesic effect of a cannabinoid agonist.     

Increased Voluntary Ethanol Consumption and Changes in Hippocampal Synaptic Plasticity in Isolated C57BL/6J Mice

Social isolation (SI) is a notable model of prolonged mild stress, characterized by multiple neurochemical and behavioral alterations, that appears particularly suitable for studying different aspects of the interplay between stress and ethanol (EtOH) consumption in order to characterize potential molecular mechanisms, including changes in the function of inhibitory GABAergic synapses, underlying such interaction. In C57BL/6J mice, SI is associated with an altered hippocampal concentration of the neuroactive steroids 3α-hydroxy-5α-pregnan-20-one (3α-5α-THP), an increased expression of the α₄ and δ subunit of γ-aminobutyric acid type A receptors (GABA_ARs) in the dentate gyrus (DG), and a parallel enhancement of the stimulatory action of 4,5,6,7-tetrahydroisoxazolo[5,4-c] pyridin-3-ol (THIP) on GABAergic tonic currents recorded in voltage-clamped DG granule cells (DGGCs). In addition, SI in C57BL/6J mice determines an increase in voluntary EtOH consumption and EtOH preference when compared to group-housed (GH) control animals. Furthermore, in hippocampal slices of SI mice we also observed a marked reduction of both cellular excitability and long term potentiation (LTP) in pyramidal neurons of the CA1 hippocampal sub-region, effects that were prevented by the long term treatment of SI mice with the neuroactive steroid precursor progesterone. In this article, we summarize some of our recent findings on the effects of SI in C57BL/6J mice on voluntary EtOH intake, regulation of GABA_ARs gene expression and function and hippocampal long term synaptic plasticity.     

Sperm ubiquitination in epididymal feline semen

Ubiquitin is a 8.5-kDa peptide that tags other proteins for proteasomal degradation. It has been proposed that ubiquitination might be responsible for the elimination of defective spermatozoa during transit through the epididymis in humans and cattle, but its exact biological function in seminal plasma has not yet been clarified. In the domestic cat (Felis catus), the percentage of immature, unviable, and abnormal spermatozoa decreases during the epididymal transit, indicating the existence of a mechanism that removes defective spermatozoa. Magnetic cell separation techniques, based on the use of magnetic beads coated with anti-ubiquitin antibodies, may allow the selective capture of ubiquitinated spermatozoa from semen, thus contributing to the identification of a potential correlation between semen quality and ubiquitination process. Moreover, the selective identification of all the ubiquitinated proteins in different epididymal regions could give a better understanding of the ubiquitin role in feline sperm maturation. The aims of this study were as follows: (1) to verify the possibility of separating ubiquitinated spermatozoa with magnetic ubiquitin beads and identify the morphological and acrosomal differences between whole sample and unbound gametes, (2) to characterize all the ubiquitinated proteins in spermatozoa retrieved in the three epididymal regions by a proteomic approach. The data indicated the presence of ubiquitinated proteins in cat epididymal semen. However, a correlation between abnormal and ubiquitinated spermatozoa has not been found, and ubiquitin cannot be considered as a biomarker of quality of epididymal feline spermatozoa. To the author's knowledge, this is the first identification of all the ubiquitinated proteins of cat spermatozoa collected from different epididymal regions. The proteomic pattern allows a further characterization of cat epididymal semen and represents a contribute to a better understanding of the ubiquitin role in feline sperm maturation.     

Cdc42 controls the dilation of the exocytotic fusion pore by regulating membrane tension

Membrane fusion underlies multiple processes, including exocytosis of hormones and neurotransmitters. Membrane fusion starts with the formation of a narrow fusion pore. Radial expansion of this pore completes the process and allows fast release of secretory compounds, but this step remains poorly understood. Here we show that inhibiting the expression of the small GTPase Cdc42 or preventing its activation with a dominant negative Cdc42 construct in human neuroendocrine cells impaired the release process by compromising fusion pore enlargement. Consequently the mode of vesicle exocytosis was shifted from full-collapse fusion to kiss-and-run. Remarkably, Cdc42-knockdown cells showed reduced membrane tension, and the artificial increase of membrane tension restored fusion pore enlargement. Moreover, inhibiting the motor protein myosin II by blebbistatin decreased membrane tension, as well as fusion pore dilation. We conclude that membrane tension is the driving force for fusion pore dilation and that Cdc42 is a key regulator of this force.     

Lead soaps formation and biodiversity in a XVIII Century wax seal coloured with minium

A multidisciplinary approach was carried out in order to study the biodeterioration and the associated microbiome of a XVIII Century wax seal coloured with minium. A small wax seal fragment was observed by scanning electron microscopy combined with energy dispersive spectroscopy in non-destructive mode. The same object was analysed by Raman and Fourier-transform infrared spectroscopy. The identification of the microbiota growing on the seal was performed with both a culture-dependent strategy, combined with hydrolytic assays, and high-throughput sequencing using the MinION platform. The whole bacterial 16S rRNA gene and the fungal markers ITS and 28S rRNA were targeted. It was observed that the carnauba wax coloured with lead tetroxide (minium) was covered by a biofilm consisting of a network of filaments and other structures of microbial origin. The culture-dependent and culture-independent investigations showed the presence of a complex microbiota composed mainly by fungal members, which demonstrated interesting properties related to lipids and lead processing. The formation of lead soaps and secondary biogenic minerals was also described.     

Stochastic multi-attribute analysis (SMAA) as an interpretation method for comparative life-cycle assessment (LCA)

Purpose

Comparative life-cycle assessments (LCAs) today lack robust methods of interpretation that help decision makers understand and identify tradeoffs in the selection process. Truncating the analysis at characterization is misleading and existing practices for normalization and weighting may unwittingly oversimplify important aspects of a comparison. This paper introduces a novel approach based on a multi-criteria decision analytic method known as stochastic multi-attribute analysis for life-cycle impact assessment (SMAA-LCIA) that uses internal normalization by means of outranking and exploration of feasible weight spaces.

Methods

To contrast different valuation methods, this study performs a comparative LCA of liquid and powder laundry detergents using three approaches to normalization and weighting: (1) characterization with internal normalization and equal weighting, (2) typical valuation consisting of external normalization and weights, and (3) SMAA-LCIA using outranking normalization and stochastic weighting. Characterized results are often represented by LCA software with respect to their relative impacts normalized to 100 %. Typical valuation approaches rely on normalization references, single value weights, and utilizes discrete numbers throughout the calculation process to generate single scores. Alternatively, SMAA-LCIA is capable of exploring high uncertainty in the input parameters, normalizes internally by pair-wise comparisons (outranking) and allows for the stochastic exploration of weights. SMAA-LCIA yields probabilistic, rather than discrete comparisons that reflect uncertainty in the relative performance of alternatives.

Results and discussion

All methods favored liquid over powder detergent. However, each method results in different conclusions regarding the environmental tradeoffs. Graphical outputs at characterization of comparative assessments portray results in a way that is insensitive to magnitude and thus can be easily misinterpreted. Typical valuation generates results that are oversimplified and unintentionally biased towards a few impact categories due to the use of normalization references. Alternatively, SMAA-LCIA avoids the bias introduced by external normalization references, includes uncertainty in the performance of alternatives and weights, and focuses the analysis on identifying the mutual differences most important to the eventual rank ordering.

Conclusions

SMAA-LCIA is particularly appropriate for comparative LCAs because it evaluates mutual differences and weights stochastically. This allows for tradeoff identification and the ability to sample multiple perspectives simultaneously. SMAA-LCIA is a robust tool that can improve understanding of comparative LCA by decision or policy makers.