Photodynamic therapy with mTHPC and polyethylene glycol-derived mTHPC: a comparative study on human tumour xenografts

The photosensitizing properties of m-tetrahydroxyphenylchlorin (mTHPC) and polyethylene glycol-derivatized mTHPC (pegylated mTHPC) were compared in nude mice bearing human malignant mesothelioma, squamous cell carcinoma and adenocarcinoma xenografts. Laser light (20 J/cm2) at 652 nm was delivered to the tumour (surface irradiance) and to an equal-sized area of the hind leg of the animals after i.p. administration of 0.1 mg/kg body weight mTHPC and an equimolar dose of pegylated mTHPC, respectively. The extent of tumour necrosis and normal tissue injury was assessed by histology. Both mTHPC and pegylated mTHPC catalyse photosensitized necrosis in mesothelioma xenografts at drug-light intervals of 1–4 days. The onset of action of pegylated mTHPC seemed slower but significantly exceeds that of mTHPC by days 3 and 4 with the greatest difference being noted at day 4. Pegylated mTHPC also induced significantly larger photonecrosis than mTHPC in squamous cell xenografts but not in adenocarcinoma at day 4, where mTHPC showed greatest activity. The degree of necrosis induced by pegylated mTHPC was the same for all three xenografts. mTHPC led to necrosis of skin and underlying muscle at a drug-light interval of 1 day but minor histological changes only at drug-light intervals from 2–4 days. In contrast, pegylated mTHPC did not result in histologically detectable changes in normal tissues under the same treatment conditions at any drug-light interval assessed. In this study, pegylated mTHPC had advantages as a photosensitizer compared to mTHPC

Stress field sensitivity analysis in a sedimentary sequence of the Alpine foreland, Northern Switzerland

The stress field at depth is a relevant parameter for the design of subsurface constructions and reservoir management. Yet the distortion of the regional stress field due to local-scale features such as sedimentary and tectonic structures or topography is often poorly constrained. We conduct a stress sensitivity analysis using 3-D numerical geomechanical modelling with an elasto-plastic material law to explore the impact of such site specific features on the stress field in a sedimentary sequence of the Swiss Alpine foreland. The model\u27s dimensions are 14 km × 14 km × 3 km and it contains ten units with different mechanical properties, intersected by two regional fault zones. An initial stress state is established involving a semi-empirical relationship between the ratio of horizontal to vertical stress and the overconsolidation ratio of argillaceous sediments. The model results indicate that local topography can affect the stress field significantly to depths greater than the relief contrasts at the surface, especially in conjunction with horizontal tectonic loading. The complexity and frictional properties of faults are also relevant. The greatest variability of the stress field arises across the different sedimentary units. Stress magnitudes and stress anisotropy are much larger in stiffer formations such as massive limestones than in softer argillaceous formations. The stiffer formations essentially carry the load of the far-field forces and are therefore more sensitive to changes of the boundary conditions. This general characteristic of stress distribution in the stiff and soft formations is broadly maintained also with progressive loading towards the plastic limit. The stress field in argillaceous sediments within a stack of formations with strongly contrasting mechanical properties like in the Alpine foreland appears to be relatively insensitive to changes in the tectonic boundary conditions and is largely controlled by the maximum stiffness contrast with respect to the load-bearing formations

Burden of postinfectious symptoms after acute Dengue, Vietnam.

We assessed predominantly pediatric patients in Vietnam with dengue and other febrile illness 3 months after acute illness. Among dengue patients, 47% reported >1 postacute symptom. Most resolved by 3 months, but alopecia and vision problems often persisted. Our findings provide additional evidence on postacute dengue burden and confirm children are affected

Rapid disease progression in a patient with mismatch repair-deficient and cortisol secreting adrenocortical carcinoma treated with pembrolizumab

Context: Metastatic adrenocortical carcinoma (ACC) is an aggressive malignancy with a poor prognosis and limited therapeutic options. A subset of ACC is due to Lynch syndrome, an inherited tumour syndrome resulting from germline mutations in mismatch repair (MMR) genes. It has been demonstrated that several cancers characterised by MMR-deficiency are sensitive to immune checkpoint inhibitors that target PD-1. Here, we provide the first report of PD-1 blockade by pembrolizumab in a patient with Lynch syndrome and progressive cortisol-secreting metastatic ACC. Case report: A 58-year old female with known Lynch syndrome who presented with severe Cushing’s syndrome was diagnosed with a cortisol-secreting ACC. Three months following surgical resection and adjuvant mitotane therapy the patient developed metastatic disease and persistent hypercortisolaemia. She commenced pembrolizumab, but her second cycle was delayed due to a transient transaminitis. Computed tomography performed after twelve weeks and 2 cycles of pembrolizumab administration revealed significant disease progression and treatment was discontinued. Seven weeks later, the patient became jaundiced and died rapidly with fulminant liver failure. Conclusion: Treatment of MMR-deficient cortisol-secreting ACC with pembrolizumab may be ineffective due to supra-physiological levels of circulating corticosteroids, which may in turn mask severe drug-induced organ damage

A critical review of the formation of mono- and dicarboxylated metabolic intermediates of alkylphenol polyethoxylates during wastewater treatment and their environmental significance

This is the author's accepted manuscript. The final published article is available from the link below. Copyright @ 2010 Taylor & Francis.Alkylphenoxyacetic acids, the metabolic biodegradation products of alkylphenol ethoxylates, are commonly found in wastewaters and sewage effluents. These persistent hydrophilic derivatives possess intrinsic estrogenic activity, which can mimic natural hormones. Their concentrations increase through the sewage treatment works as a result of biodegradation and biotransformation, and when discharged can disrupt endocrine function in fish. These acidic metabolites represent the dominant alkylphenolic compounds found in wastewater effluent and their presence is cause for concern as, potentially, through further biotransformation and biodegradation, they can act as sources of nonylphenol, which is toxic and estrogenic. The authors aim to assess the mechanisms of formation as well as elimination of alkylphenoxyacetic acids within conventional sewage treatment works with the emphasis on the activated sludge process. In addition, they evaluate the various factors influencing their degradation and formation in laboratory scale and full-scale systems. The environmental implications of these compounds are considered, as is the need for tertiary treatment processes for their removal

Automatic multi-seed detection for MR breast image segmentation

In this paper an automatic multi-seed detection method for magnetic resonance (MR) breast image segmentation is presented. The proposed method consists of three steps: (1) pre-processing step to locate three regions of interest (axillary and sternal regions); (2) processing step to detect maximum concavity points for each region of interest; (3) breast image segmentation step. Traditional manual segmentation methods require radiological expertise and they usually are very tiring and time-consuming. The approach is fast because the multi-seed detection is based on geometric properties of the ROI. When the maximum concavity points of the breast regions have been detected, region growing and morphological transforms complete the segmentation of breast MR image. In order to create a Gold Standard for method effectiveness and comparison, a dataset composed of 18 patients is selected, accordingly to three expert radiologists of University of Palermo Policlinico Hospital (UPPH). Each patient has been manually segmented. The proposed method shows very encouraging results in terms of statistical metrics (Sensitivity: 95.22%; Specificity: 80.36%; Precision: 98.05%; Accuracy: 97.76%; Overlap: 77.01%) and execution time (4.23 s for each slice)

Analysis of pharmaceuticals in wastewater and removal using a membrane bioreactor

Much attention has recently been devoted to the life and behaviour of pharmaceuticals in the water cycle. In this study the behaviour of several pharmaceutical products in different therapeutic categories (analgesics and anti-inflammatory drugs, lipid regulators, antibiotics, etc.) was monitored during treatment of wastewater in a laboratory-scale membrane bioreactor (MBR). The results were compared with removal in a conventional activated-sludge (CAS) process in a wastewater-treatment facility. The performance of an MBR was monitored for approximately two months to investigate the long-term operational stability of the system and possible effects of solids retention time on the efficiency of removal of target compounds. Pharmaceuticals were, in general, removed to a greater extent by the MBR integrated system than during the CAS process. For most of the compounds investigated the performance of MBR treatment was better (removal rates >80%) and effluent concentrations of, e.g., diclofenac, ketoprofen, ranitidine, gemfibrozil, bezafibrate, pravastatin, and ofloxacin were steadier than for the conventional system. Occasionally removal efficiency was very similar, and high, for both treatments (e.g. for ibuprofen, naproxen, acetaminophen, paroxetine, and hydrochlorothiazide). The antiepileptic drug carbamazepine was the most persistent pharmaceutical and it passed through both the MBR and CAS systems untransformed. Because there was no washout of biomass from the reactor, high-quality effluent in terms of chemical oxygen demand (COD), ammonium content (N-NH(4)), total suspended solids (TSS), and total organic carbon (TOC) was obtained

An evolutionarily conserved mechanism for cAMP elicited axonal regeneration involves direct activation of the dual leucine zipper kinase DLK

A broadly known method to stimulate the growth potential of axons is to elevate intracellular levels of cAMP, however the cellular pathway(s) that mediate this are not known. Here we identify the Dual Leucine-zipper Kinase (DLK, Wnd in Drosophila) as a critical target and effector of cAMP in injured axons. DLK/Wnd is thought to function as an injury ‘sensor’, as it becomes activated after axonal damage. Our findings in both Drosophila and mammalian neurons indicate that the cAMP effector kinase PKA is a conserved and direct upstream activator of Wnd/DLK. PKA is required for the induction of Wnd signaling in injured axons, and DLK is essential for the regenerative effects of cAMP in mammalian DRG neurons. These findings link two important mediators of responses to axonal injury, DLK/Wnd and cAMP/PKA, into a unified and evolutionarily conserved molecular pathway for stimulating the regenerative potential of injured axons. DOI: http://dx.doi.org/10.7554/eLife.14048.00

Humanization of robots: is it really such a good idea?

The aim of this review was to examine the pros and cons of humanizing social robots following a psychological perspective. As such, we had six goals. First, we defined what social robots are. Second, we clarified the meaning of humanizing social robots. Third, we presented the theoretical backgrounds for promoting humanization. Fourth, we conducted a review of empirical results of the positive effects and the negative effects of humanization on human–robot interaction (HRI). Fifth, we presented some of the political and ethical problems raised by the humanization of social robots. Lastly, we discussed the overall effects of the humanization of robots in HRI and suggested new avenues of research and development.info:eu-repo/semantics/publishedVersio