Overview on topical 5-ALA photodynamic therapy use for non melanoma skin cancers

Ultraviolet radiation (UV) contributes to a variety of skin diseases including inflammation, degenerative aging, and cancer. Historically, humans have been exposed to UV radiation mainly through occupational exposure; recreational UV exposure, however, has increased dramatically in recent years, because of outdoor leisure activities and to purposely tan for cosmetic purposes. Both UVB and UVA radiation have been shown to cause DNA damage and immunosuppression, the important forms of biological damage that lead to NMSC. Nonmelanoma skin cancer (NMSC) is the most common malignancy, whose public health significance is often unrecognized which continues to grow at an alarming rate, becoming an occupational disease. Available treatments alternative to surgery include photodynamic therapy, electrochemotherapy, cryotherapy, ablative lasers, 5-fluorouracil, imiquimod, ingenol mebutate, and diclofenac. Among these, photodynamic therapy is a noninvasive technique with excellent cosmetic outcome and good curative results, when used in initial stages of skin cancers for superficial lesions. It is administered under numerous and significantly varied regimens and there are a wide range of cure rates reported, permitting treatment of large and multiple lesions with excellent cosmetic results. This is an overview of photodynamic applications especially for the treatment of NMSC, with a short focus on daylight modality. © 2014 Carmen Cantisani et al

GNAO1 encephalopathy: broadening the phenotype and evaluating treatment and outcome

OBJECTIVE: To describe better the motor phenotype, molecular genetic features, and clinical course of GNAO1-related disease. METHODS: We reviewed clinical information, video recordings, and neuroimaging of a newly identified cohort of 7 patients with de novo missense and splice site GNAO1 mutations, detected by next-generation sequencing techniques. RESULTS: Patients first presented in early childhood (median age of presentation 10 months, range 0-48 months), with a wide range of clinical symptoms ranging from severe motor and cognitive impairment with marked choreoathetosis, self-injurious behavior, and epileptic encephalopathy to a milder phenotype, featuring moderate developmental delay associated with complex stereotypies, mainly facial dyskinesia and mild epilepsy. Hyperkinetic movements were often exacerbated by specific triggers, such as voluntary movement, intercurrent illnesses, emotion, and high ambient temperature, leading to hospital admissions. Most patients were resistant to drug intervention, although tetrabenazine was effective in partially controlling dyskinesia for 2/7 patients. Emergency deep brain stimulation (DBS) was life saving in 1 patient, resulting in immediate clinical benefit with complete cessation of violent hyperkinetic movements. Five patients had well-controlled epilepsy and 1 had drug-resistant seizures. Structural brain abnormalities, including mild cerebral atrophy and corpus callosum dysgenesis, were evident in 5 patients. One patient had a diffuse astrocytoma (WHO grade II), surgically removed at age 16. CONCLUSIONS: Our findings support the causative role of GNAO1 mutations in an expanded spectrum of early-onset epilepsy and movement disorders, frequently exacerbated by specific triggers and at times associated with self-injurious behavior. Tetrabenazine and DBS were the most useful treatments for dyskinesia

Anti-TNF-α drugs differently affect the TNFa-sTNFR system and monocyte subsets in patients with psoriasis

TNF-a has a central role in the development and maintenance of psoriatic plaques, and its serum levels correlate with disease activity. Anti-TNF-a drugs are, however, ineffective in a relevant percentage of patients for reasons that are currently unknown. To understand whether the response to anti-TNF-a drugs is influenced by the production of anti-drug antibodies or by the modulation of the TNFa-TNFa receptor system, and to identify changes in monocyte phenotype and activity, we analysed 119 psoriatic patients who either responded or did not respond to different anti-TNF-a therapies (adalimumab, etanercept or infliximab), and measured plasma levels of TNF-a, TNF-a soluble receptors, drug and anti-drug antibodies. Moreover, we analyzed the production of TNF-a and TNF-α soluble receptors by peripheral blood mononuclear cells (PBMCs), and characterized different monocyte populations. We found that: i) the drug levels varied between responders and non-responders; ii) anti-infliximab antibodies were present in 15% of infliximab-treated patients, while anti-etanercept or anti-adalimumab antibodies were never detected; iii) plasma TNF-a levels were higher in patients treated with etanercept compared to patients treated with adalimumab or infliximab; iv) PBMCs from patients responding to adalimumab and etanercept produced more TNF-a and sTNFRII in vitro than patients responding to infliximab; v) PBMCs from patients not responding to infliximab produce higher levels of TNF-a and sTNFRII than patients responding to infliximab; vi) anti- TNF-a drugs significantly altered monocyte subsets. A complex remodelling of the TNFa-TNFa receptor system thus takes place in patients treated with anti-TNF-α drugs, that involves either the production of anti-drug antibodies or the modulation of monocyte phenotype or inflammatory activity

Surgical site infection after caesarean section. Space for post-discharge surveillance improvements and reliable comparisons

Surgical site infections (SSI) after caesarean section (CS) represent a substantial health system concern. Surveying SSI has been associated with a reduction in SSI incidence. We report the findings of three (2008, 2011 and 2013) regional active SSI surveillances after CS in community hospital of the Latium region determining the incidence of SSI. Each CS was surveyed for SSI occurrence by trained staff up to 30 post-operative days, and association of SSI with relevant characteristics was assessed using binomial logistic regression. A total of 3,685 CS were included in the study. A complete 30 day post-operation follow-up was achieved in over 94% of procedures. Overall 145 SSI were observed (3.9% cumulative incidence) of which 131 (90.3%) were superficial and 14 (9.7%) complex (deep or organ/space) SSI; overall 129 SSI (of which 89.9% superficial) were diagnosed post-discharge. Only higher NNIS score was significantly associated with SSI occurrence in the regression analysis. Our work provides the first regional data on CS-associated SSI incidence, highlighting the need for a post-discharge surveillance which should assure 30 days post-operation to not miss data on complex SSI, as well as being less labour intensive

The effectiveness of high-resolution LiDAR data combined with PSInSAR data in landslide study

The spatial resolution of digital elevation models (DEMs) is an important factor for reliable landslide studies. Multi-interferometric techniques such as persistent scatterer interferometric synthetic aperture radar (PSInSAR) are used to evaluate the landslide state of activity and its ground deformation velocity, which is commonly measured along the satellite line of sight (LOS). In order to compare velocities measured by different satellites in different periods, their values can be projected along the steepest slope direction, which is the most probable direction of real movement. In order to achieve this result, DEM-derived products are needed. In this paper, the effectiveness of different DEM resolutions was evaluated in order to project ground deformation velocities measured by means of PSInSAR technique in two different case studies in the Messina Province (Sicily, southern Italy): San Fratello and Giampilieri. Three DEMs were used: (i) a 20-m resolution DEM of the Italian Military Geographic Institute (IGM), (ii) a 2-m resolution DEM derived from airborne laser scanning (ALS) light detection and ranging (LiDAR) data for the San Fratello 2010 landslide, and (iii) a 1-m resolution DEM derived from ALS LiDAR data for the area of Giampilieri. The evaluation of the applied method effectiveness was performed by comparing the DEMs elevation with those of each single permanent scatterer (PS) and projecting the measured velocities along the steepest slope direction. Results highlight that the higher DEM resolution is more suitable for this type of analysis; in particular, the PS located nearby the watershed divides is affected by geometrical problems when their velocities are projected along the steepest slope

Multi-Temporal Evaluation of Landslide Movements and Impacts on Buildings in San Fratello (Italy) By Means of C-Band and X-Band PSI Data

This work provides a multi-temporal and spatial investigation of landslide effects in the San Fratello area (Messina province within the Sicily region, Italy), by means of C-band and X-band Persistent Scatterer Interferometry (PSI) data, integrated with in situ field checks and a crack pattern survey. The Sicily region is extensively affected by hydrogeological hazards since several landslides regularly involved local areas across time. In particular, intense and catastrophic landslide phenomena have recently occurred in the San Fratello area; the last event took place in February 2010, causing large economic damage. Thus, the need for an accurate ground motions and impacts mapping and monitoring turns out to be significantly effective, in order to better identify active unstable areas and to help proper risk-mitigation measures planning. The combined use of historical and recent C-band satellites and current X-band Synthetic Aperture Radar sensors of a new generation permits spatially and temporally detection of landslide-induced motions on a local scale and to properly provide a complete multi-temporal evaluation of their effects on the area of interest. PSI ground motion rates are cross-compared with local failures and damage of involved buildings, recently recognized by in situ observations. As a result, the analysis of landslide-induced movements over almost 20 years and the validation of radar data with manufactured crack patterns, permits one to finally achieve a complete and reliable assessment in the San Fratello test site

Updated landslide inventory of the area between the Furiano and Rosmarino creeks (Sicily, Italy)

A 1:10,000 scale landslide inventory map has been prepared for the area between the Furiano and Rosmarino creeks, in the Nebrodi Mountains (north-eastern Sicily, Italy), a territory highly prone to slope failures, due to the local geological and geomorphological settings and intense rainfall. The landslide inventory database included within the Hydrogeological Setting Plan of the Sicily Region has been used as a starting point for this work. The updated inventory map has been compiled through a combination of conventional approaches (i.e. aerial photo-interpretation and field surveys) and new remote sensing techniques (ground deformation measurements obtained by interferometric analysis of satellite Synthetic Aperture Radar images). The new landslide inventory consists of 566 events, classified according to their typology and state of activity

Corrigendum to "Overview on Topical 5-ALA Photodynamic Therapy Use for Non Melanoma Skin Cancers"

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Methanolic Extract of the Nutritional Plant (Diospyros kaki Thunb.) Exhibits Anticancer Activity by Inducing Mitochondrial Dysfunction in Colorectal Cancer Cells

Background/Objectives: Diospyros kaki, the most widely cultivated species of persimmon, has been long used in traditional medicine since its leaves’ extracts contain high amounts of flavonoids and terpenoids, endowed with several beneficial effects. However, its anticancer activity towards colorectal cancer (CRC) has not been investigated in depth. Methods: The effect of a methanolic extract of D. kaki leaves, rich in kaempferol and quercetin derivatives, have been evaluated on an E705 CRC cell line, representative of most CRC patients, and on SW480 cells, carrying a KRAS-activating mutation. Results: This extract is effective in reducing tumor cells’ viability without affecting the healthy mucosa cell line CCD 841. In fact, Western blot experiments showed its ability to induce apoptosis in cancer cells by increasing oxidative stress and disrupting mitochondrial functionality, as shown by reactive oxygen species measurement and Seahorse analysis. Conclusions: With the aim of increasing healthspan, as well as the substantial societal and macroeconomic costs associated with cancer, our results could pave the way to a role for D. kaki extract in both CRC treatment and prevention

Impaired Mitochondrial Morphology and Functionality in Lonp1wt/- Mice

LONP1 is a nuclear-encoded mitochondrial protease crucial for organelle homeostasis; mutations ofLONP1have been associated with Cerebral, Ocular, Dental, Auricular, and Skeletal anomalies (CODAS) syndrome. To clarify the role of LONP1 in vivo, we generated a mouse model in whichLonp1was ablated. The homozygousLonp(-/-)mouse was not vital, while the heterozygousLonp1(wt/-)showed similar growth rate, weight, length, life-span and histologic features as wild type. Conversely, ultrastructural analysis of heterozygous enterocytes evidenced profound morphological alterations of mitochondria, which appeared increased in number, swollen and larger, with a lower complexity. Embryonic fibroblasts (MEFs) fromLonp1(wt/-)mice showed a reduced expression ofLonp1andTfam, whose expression is regulated by LONP1. Mitochondrial DNA was also reduced, and mitochondria were swollen and larger, albeit at a lesser extent than enterocytes, with a perinuclear distribution. From the functional point of view, mitochondria from heterozygous MEF showed a lower oxygen consumption rate in basal conditions, either in the presence of glucose or galactose, and a reduced expression of mitochondrial complexes than wild type. In conclusion, the presence of one functional copy of theLonp1gene leads to impairment of mitochondrial ultrastructure and functions in vivo