Increased tumour dihydroceramide production after Photofrin-PDT alone and improved tumour response after the combination with the ceramide analogue LCL29. Evidence from mouse squamous cell carcinomas

Photodynamic therapy (PDT) has been proven effective for treatment of several types of cancer. Photodynamic therapy alone, however, attains limited cures with some tumours and there is need for its improved efficacy in such cases. Sphingolipid (SL) analogues can promote tumour response in combination with anticancer drugs. In this study, we used mouse SCCVII squamous cell carcinoma tumours to determine the impact of Photofrin-PDT on the in vivo SL profile and the effect of LCL29, a C6-pyridinium ceramide, on PDT tumour response. Following PDT, the levels of dihydroceramides (DHceramides), in particular C20-DHceramide, were elevated in tumours. Similarly, increases in DHceramides, in addition to C20:1-ceramide, were found in PDT-treated SCCVII cells. These findings indicate the importance of the de novo ceramide pathway in Photofrin-PDT response not only in cells but also in vivo. Notably, co-exposure of SCCVII tumours to Photofrin-PDT and LCL29 led to enhanced tumour response compared with PDT alone. Thus, we show for the first time that Photofrin-PDT has a distinct signature effect on the SL profile in vitro and in vivo, and that the combined treatment advances PDT therapeutic gain, implying translational significance of the combination

Mitochondrially targeted ceramide LCL-30 inhibits colorectal cancer in mice

The sphingolipid ceramide is intimately involved in the growth, differentiation, senescence, and death of normal and cancerous cells. Mitochondria are increasingly appreciated to play a key role in ceramide-induced cell death. Recent work showed the C16-pyridinium ceramide analogue LCL-30 to induce cell death in vitro by mitochondrial targeting. The aim of the current study was to translate these results to an in vivo model. We found that LCL-30 accumulated in mitochondria in the murine colorectal cancer cell line CT-26 and reduced cellular ATP content, leading to dose- and time-dependent cytotoxicity. Although the mitochondrial levels of sphingosine-1-phosphate (S1P) became elevated, transcription levels of ceramide-metabolising enzymes were not affected. In mice, LCL-30 was rapidly absorbed from the peritoneal cavity and cleared from the circulation within 24 h, but local peritoneal toxicity was dose-limiting. In a model of subcutaneous tumour inoculation, LCL-30 significantly reduced the proliferative activity and the growth rate of established tumours. Sphingolipid profiles in tumour tissue also showed increased levels of S1P. In summary, we present the first in vivo application of a long-chain pyridinium ceramide for the treatment of experimental metastatic colorectal cancer, together with its pharmacokinetic parameters. LCL-30 was an efficacious and safe agent. Future studies should identify an improved application route and effective partners for combination treatment

A data-driven synthesis of research evidence for domains of hearing loss, as reported by adults with hearing loss and their communication partners

A number of assessment tools exist to evaluate the impact of hearing loss, with little consensus among researchers as to either preference or psychometric adequacy. The item content of hearing loss assessment tools should seek to capture the impact of hearing loss on everyday life, but to date no one has synthesized the range of hearing loss complaints from the perspectives of the person with hearing loss and their communication partner. The current review aims to synthesize the evidence on person with hearing loss- and communication partner-reported complaints of hearing loss. Searches were conducted in Cos Conference Papers Index, the Cumulative Index to Nursing and Allied Health Literature, Excerpta Medica Database, PubMed, Web of Science, and Google Scholar to identify publications from May 1982 to August 2015. A manual search of four relevant journals updated the search to May 2017. Of the 9,516 titles identified, 78 records (comprising 20,306 participants) met inclusion criteria and were taken through to data collection. Data were analyzed using meta-ethnography to form domains representing the person with hearing loss- and communication partner-reported complaints of hearing loss as reported in research. Domains and subdomains mutual to both perspectives are related to ‘‘Auditory’’ (listening, communicating, and speaking), ‘‘Social’’ (relationships, isolation, social life, occupational, and interventions), and ‘‘Self’’ (effort and fatigue, emotions, identity, and stigma). Our framework contributes fundamental new knowledge and a unique resource that enables researchers and clinicians to consider the broader impacts of hearing loss. Our findings can also be used to guide questions during diagnostic assessment and to evaluate existing measures of hearing loss

Is complementary and alternative medicine (CAM) cost-effective? a systematic review

BACKGROUND: Out-of-pocket expenditures of over $34 billion per year in the US are an apparent testament to a widely held belief that complementary and alternative medicine (CAM) therapies have benefits that outweigh their costs. However, regardless of public opinion, there is often little more than anecdotal evidence on the health and economic implications of CAM therapies. The objectives of this study are to present an overview of economic evaluation and to expand upon a previous review to examine the current scope and quality of CAM economic evaluations. METHODS: The data sources used were Medline, AMED, Alt-HealthWatch, and the Complementary and Alternative Medicine Citation Index; January 1999 to October 2004. Papers that reported original data on specific CAM therapies from any form of standard economic analysis were included. Full economic evaluations were subjected to two types of quality review. The first was a 35-item checklist for reporting quality, and the second was a set of four criteria for study quality (randomization, prospective collection of economic data, comparison to usual care, and no blinding). RESULTS: A total of 56 economic evaluations (39 full evaluations) of CAM were found covering a range of therapies applied to a variety of conditions. The reporting quality of the full evaluations was poor for certain items, but was comparable to the quality found by systematic reviews of economic evaluations in conventional medicine. Regarding study quality, 14 (36%) studies were found to meet all four criteria. These exemplary studies indicate CAM therapies that may be considered cost-effective compared to usual care for various conditions: acupuncture for migraine, manual therapy for neck pain, spa therapy for Parkinson's, self-administered stress management for cancer patients undergoing chemotherapy, pre- and post-operative oral nutritional supplementation for lower gastrointestinal tract surgery, biofeedback for patients with "functional" disorders (eg, irritable bowel syndrome), and guided imagery, relaxation therapy, and potassium-rich diet for cardiac patients. CONCLUSION: Whereas the number and quality of economic evaluations of CAM have increased in recent years and more CAM therapies have been shown to be of good value, the majority of CAM therapies still remain to be evaluated

What is the effect of subepithelial lesions of the esophagus on esophageal motility?

© 2022 European Review for Medical and Pharmacological Sciences. All rights reserved.OBJECTIVE: Esophageal motility is regulated both by coordinated stimulation and inhibition of the circular and longitudinal muscle layers of the esophagus. Although there are many diseases known to have an effect on esophageal motility, the effect of subepithelial lesions (SELs) of the esophagus on esophageal motility, which is often detected incidentally, remains still unclear. The aim of this study is to reveal the effect of SELs of the esophagus on esophageal motility evaluating it by high-resolution manometry (HRM). PATIENTS AND METHODS: A total of 32 patients with SELs in the esophagus and 12 healthy individuals were included. All patients and controls included in the study underwent HRM using a Unisensor UniTip High Resolution catheter (Laborie, Amsterdam, Netherlands) and endosonographic examination. RESULTS: The mean age was 52.60±15.56 years (range: 23-79) and the average body mass index (BMI) was 26.63±4.71 kg/m2. Gender, height, weight, and BMI measurements, smoking status, alcohol use, and DM status did not statistically differ significantly between the groups (p>0.05). Of 32 patients with SELs, 65.6% (n=21) had lesions originating in the muscularis propria, while 34.4% had lesions originating in the submucosa. The rate of abnormal motility both in the supine and in upright positions of patients with SELs was found to be significantly higher than in the control group (p=0.001, p2 cm), the probability of abnormal HRM results increased. CONCLUSIONS: SELs of the esophagus have pathological effects on esophageal motility, mainly ineffective esophageal motility disorder

A new approach for developing comprehensive agricultural drought index using satellite-derived biophysical parameters and factor analysis method

The accurate assessment of drought and its monitoring is highly depending on the selection of appropriate indices. Despite the availability of countless drought indices, due to variability in environmental properties, a single universally drought index has not been presented yet. In this study, a new approach for developing comprehensive agricultural drought index from satellite-derived biophysical parameters is presented. Therefore, the potential of satellite-derived biophysical parameters for improved understanding of the water status of pistachio (Pistachio vera L.) crop grown in a semiarid area is evaluated. Exploratory factor analysis with principal component extraction method is performed to select the most in?uential parameters from seven biophysical parameters including surface temperature (Ts), surface albedo (a), leaf area index (LAI), soil heat ?ux (Go), soil-adjusted vegetation index (SAVI), normalized difference vegetation index (NDVI), and net radiation (Rn). Ts and Gowere found as the most effective parameters by this method. However, Ts, LAI, a, and SAVI that accounts for 99.6 % of the total variance of seven inputs were selected to model a new biophysical water stress index (BPWSI). The values of BPWSI were stretched independently and compared with the range of actual evapotranspiration estimated through well-known METRIC (mapping evapotranspiration at high resolution with internal calibration) energy balance model. The results showed that BPWSI can be ef?ciently used for the prediction of the pistachio water status (RMSE of 0.52, 0.31, and 0.48 mm/day on three image dates of April 28, July 17, and August 2, 2010). The study con?rmed that crop water status is accounted by several satellite-based biophysical parameters rather than single parameter