Enhancing tumor's skin photothermal therapy using Gold nanoparticles : a Monte Carlo simulation.

The aim of this study is to investigate how the introduction of Gold nanoparticles GNPs into a skin tumor affects the ability to absorb laser light during multicolor laser exposure. The Monte Carlo Geant4 technique was used to construct a cubic geometry simulating human skin, and a 5 mm tumor spheroid was implanted at an adjustable depth x. Our findings show that injecting a very low concentration of 0.01% GNPs into a tumor located 1 cm below the skin's surface causes significant laser absorption of up to 25%, particularly in the 900 nm to 1200 nm range, resulting in a temperature increase of approximately 20%. It is an effective way to raise a tumor's temperature and cause cell death while preserving healthy cells. The addition of GNPs to a tumor during polychromatic laser exposure with a wavelength ranging from 900 nm to 1200 nm increases laser absorption and thus temperature while preserving areas without GNPs.

Epidemiology of breast cancer in women based on diagnosis data from oncologists and senologists in Algeria.

BACKGROUND: Breast cancer (BC) is a major health issue threatening women's life. No reliable epidemiological data on BC diagnosed by oncologists/senologists are available in Algeria. METHODS: The BreCaReAl study, a non-interventional prospective cohort study, included adult women with confirmed BC in Algeria. Disease incidence, patients and disease characteristics, treatment patterns, and mortality rate were recorded up to 12 months of follow-up. RESULTS: Overall, 1,437 patients were analysed: median age was 48 [41;57] years and 337 (23.5%) women had a family history of BC. BC incidence was 22.3 (95% CI: 21.5; 23.2) cases per 100,000 inhabitants over 8 months. Delayed diagnosis was reported in 400 (29.2%) patients. First line of treatments were mainly chemotherapy and surgery. Twenty-eight serious adverse events were reported including 10 (37.0%) events which led to death. Mortality rate reached 3.2% at 12 months CONCLUSION: A delayed diagnosis highlights the importance of implementing more effective screening strategies.

Review of basal-plus insulin regimen options for simpler insulin intensification in people with Type 2 diabetes mellitus.

AIMS: To identify simple insulin regimens for people with Type 2 diabetes mellitus that can be accepted and implemented earlier in primary and specialist care, taking into consideration each individual's needs and capabilities. METHODS: Using randomized clinical trials identified by a search of the PubMed database, as well as systematic reviews, meta-analyses and proof-of-concept studies, this review addresses topics of interest related to the progressive intensification of a basal insulin regimen to a basal-plus regimen (one basal insulin injection plus stepwise addition of one to three preprandial short-acting insulin injections/day) vs a basal-bolus regimen (basal insulin plus three short-acting insulin injections per day) in people with Type 2 diabetes. The review explores approaches that can be used to define the meal for first prandial injection with basal-plus regimens, differences among insulin titration algorithms, and the importance of self-motivation and autonomy in achieving optimum glycaemic control. RESULTS: A basal-plus regimen can provide glycaemic control equivalent to that obtained with a full basal-bolus regimen, with fewer injections of prandial insulin. The first critical step is to optimize basal insulin dosing to reach a fasting glucose concentration of ~6.7 mmol/l; this allows ~40% of patients with baseline HbA1c >75 mmol/mol (9%) to be controlled with only one basal insulin injection per day. CONCLUSIONS: Compared with a basal-bolus regimen, a basal-plus insulin regimen is as effective but more practical, and has the best chance of acceptance and success in the real world.

Phenotypic Resistance to Disinfectants and Antibiotics in Methicillin-Resistant Staphylococcus aureus Strains Isolated from Pigs.

The aim of this research was to study the phenotypic resistances to disinfectants and antibiotics in strains of methicillin-resistant Staphylococcus aureus (MRSA) obtained from Canary black pigs. Analyses were performed on 54 strains of MRSA, isolated in Canary black pigs from the province of Tenerife (Spain); all of them carried the mecA gene. The strains were isolated by means of nasal swab samples of healthy pigs, collected under veterinarian supervision. Bactericidal activity of antiseptics and disinfectants was tested by means of the dilution-neutralization method. Susceptibility to the disinfectants glutaraldehyde, peracetic acid and silver nitrate was assessed, as well as to the antiseptics chlorhexidine, benzalkonium chloride and povidone iodine. Susceptibility to a wide array of antibiotics representing the main groups was determined by means of the disc diffusion method. All the strains demonstrated susceptibility to the disinfectants tested at the recommended concentration, and even to dilutions equal to or lesser than 1/16. The most effective antiseptic and disinfectant were, respectively, chlorhexidine and silver nitrate. With regard to the antibiotics, the strains proved to be multiresistant. All presented phenotypic resistance to the ß-lactam antibiotics ampicillin, penicillin and cefoxitin, as well as to numerous aminoglycosides, tetracycline and trimethoprim-sulfamethoxazole. It was also observed that 61.1% of the strains were carriers of plasmids. Our results underline that in the strains such as MRSA, which show multiple resistances to antibiotics, the antiseptics and disinfectants show great efficacy. Moreover, as other authors also suggest, for the treatment and prevention of infections caused by MRSA, the use of ß-lactam and aminoglycoside antibiotics may be less effective.

Albendazole sulphoxide kinetic disposition after treatment with different formulations in dogs.

New therapeutic strategies based on the search of alternative formulations of albendazole (ABZ) and albendazole sulphoxide (ABZSO) are under current development to optimize posology and antiparasite efficacy in dogs. In an incomplete block design, nine dogs were randomly divided into three groups (n = 6). Treatments were carried out in two phases as follows. Phase I: Group I (treatment A), animals received ABZ at 25 mg/kg of conventional formulation. Group II (treatment B), dogs received 25 mg/kg of a modified poloxamer-ABZ formulation. Group III (treatment C), animals were treated with ABZSO in equimolar amount to ABZ doses. After 21 days of wash-out period the experiment was repeated (Phase II). Blood samples were collected over 24 h and subsequently analysed by high performance liquid chromatography. ABZSO and ABZSO(2) were the analytes recovered in plasma. Significant higher (P < 0.001) ABZSO area under the concentration-time curve (+500%) and C(max) (+487%) values were obtained for the treatment C in comparison with treatments A and B. However, no statistical differences on pharmacokinetic parameters were found between formulations A and B. In conclusion, the enhanced plasma concentration profile obtained for the ABZSO formulation used in treatment C may contribute to optimize the anthelmintic control in dogs.

The critical barrier to progress in dentine bonding with the etch-and-rinse technique.

OBJECTIVES: The lack of durability in resin-dentine bonds led to the use of chlorhexidine as MMP-inhibitor to prevent the degradation of hybrid layers. Biomimetic remineralisation is a concept-proven approach in preventing the degradation of resin-dentine bonds. The purpose of this study is to examine the integrity of aged resin-dentine interfaces created with a nanofiller-containing etch-and-rinse adhesive after the application of these two approaches. METHODS: The more established MMP-inhibition approach was examined using a parallel in vivo and in vitro ageing design to facilitate comparison with the biomimetic remineralisation approach using an in vitro ageing design. Specimens bonded without chlorhexidine exhibited extensive degradation of the hybrid layer after 12 months of in vivo ageing. RESULTS: Dissolution of nanofillers could be seen within a water-rich zone within the adhesive layer. Although specimens bonded with chlorhexidine exhibited intact hybrid layers, water-rich regions remained in those hybrid layers and degradation of nanofillers occurred within the adhesive layer. Specimens subjected to in vitro biomimetic remineralisation followed by in vitro ageing demonstrated intrafibrillar collagen remineralisation within hybrid layers and deposition of mineral nanocrystals in nanovoids within the adhesive. CONCLUSIONS: The impact was realized by understanding the lack of an inherent mechanism to remove water from resin-dentine interfaces as the critical barrier to progress in bonding with the etch-and-rinse technique. The experimental biomimetic remineralisation strategy offers a creative solution for incorporating a progressive hydration mechanism to achieve this goal, which warrants its translation into a clinically applicable technique.

Direct quantification of mitochondrial DNA and its 4.9-kb common deletion without DNA purification.

Quantitative analysis of mitochondrial DNA (mtDNA) and its common deletion (CD) are sensitive and early markers for mitochondrial mutations and suffering. However, the use of purified DNA can lead to quantification errors because of variable DNA extraction yields due to the significant differences in size and structure between genomic DNA (gDNA) and mtDNA. We report a real-time qPCR-based protocol directly on tissue lysate, without DNA extraction. This method, which allows both absolute and relative measure, increases the measuring accuracy of the mtDNA/gDNA ratio and leads to reliable and more reproducible results when measuring the deleted/total mtDNA ratio.

In vivo chlorhexidine stabilization of hybrid layers of an acetone-based dentin adhesive.

The current in vivo study evaluated the degradation of dentin hybrid layers in deep occlusal-surface resin composite restorations using TEM. Caries-free premolars scheduled for extraction as part of orthodontic treatment were prepared and restored, then extracted after 12 months. The adhesive used was a single-bottle etch-and-rinse acetone-based product (Prime & Bond NT, Dentsply/Caulk). Control group restorations (n=8) were placed according to the manufacturer's instructions, while the experimental group received application of a 2% solution of chlorhexidine digluconate after etching and rinsing and prior to application of the adhesive. Extensive degradation was observed in all of the teeth in the control group after 12 months, while no degradation was observed in the experimental group. In vitro testing showed no significant difference in immediate microtensile bond strength between the control and experimental adhesive protocols.

Effect of arch length on the functional well-being of dentate adults.

The aim of this study was to assess the influence of arch length and the number of occlusal units on the oral functions and general satisfaction perceived by dentate adults without dentures who had all their aesthetic units intact. We performed an epidemiological study at randomly chosen health centres on populations of adults without dentures. The subjects (n = 624) were classified as complete dental arch (CDA), interrupted dental arch (IDA) or shortened dental arches (SDA), depending on the length and continuity of the dental arches. We gathered clinical data and data on functional ability and oral satisfaction, plotting them on a scale of 0-10. The individuals with a shortened dental arch were found to have longer-lasting, more frequent and more severe functional limitations upon chewing, smiling and speaking than those with a complete or interrupted arch. The prevalance rate ratio (95% CI) of functional limitations in the SDA group was higher than in the aggregated CDA-IDA group, the values ranging between 1.56 (1.22-12.01) as regards chewing and 2.35 (1.45-3.85) in the case of smiling. However, in general all groups were satisfied with their oral status.

Breast inflammatory gigantomastia in a context of immune-mediated diseases.

CONTEXT: Localized breast lesions have been described in lupic or diabetic patients. However, the description of breast gigantomastia in women presenting with autoimmune diseases has not been reported. SETTING: The study took place within the Department of Endocrinology and Reproductive Medicine, Necker Hospital, Paris, France. PATIENTS: We describe eight patients with inflammatory gigantomastia, occurring in a context of immune-mediated diseases: myasthenia, chronic arthritis, or thyroiditis. MAIN OUTCOME MEASURES: Together with hormonal, immunological, and breast magnetic resonance imaging (MRI) evaluation, breast histology enabled us to perform immunocytochemical and indirect immunofluorescence studies. Control sera were obtained from patients with (n = 10) and without (n = 7) antinuclear antibodies. RESULTS: Six of the eight patients developed gigantomastia either at puberty or during pregnancy. Neither a hormonal oversecretion nor a specific immunological pattern was observed. All patients except one presented antinuclear antibodies. Histological study revealed a diffuse, stromal hyperplasia and a severe atrophy of the lobules. A rarefaction of adipocytes was also noted, as previously suggested on MRI. There was a perilobular lymphocytic infiltrate made of CD3+ lymphocytes. Study of sera from five of six cases of gigantomastia showed a nuclear immunofluorescence pattern in normal mammary ductal and lobular glandular epithelium, as well as in kidney and intestine epithelial cells. In control sera, a nuclear signal was observed only when antinuclear antibodies were present. CONCLUSIONS: We suggest that breast tissue may be a target tissue in autoimmune diseases, this process being favored by the hormonal milieu. However, the precise mechanism of such association is not individualized. The fact that stromal hyperplasia is the main histological feature justifies the search for the involvement of growth factors in such a process.

One-year clinical performance of a resin-modified glass ionomer and a resin composite restorative material in unprepared Class V restorations.

This study evaluated the clinical performance and appearance of a resin-modified glass ionomer and a resin composite over one year. Thirty-seven pairs of restorations of Fuji II LC and Z250/Single Bond were placed in caries-free cervical erosion/abfraction lesions without tooth preparation. Restorations were clinically evaluated at baseline and 6 and 12 months, using modified Ryge/USPHS criteria. No significant difference (p>0.05) was observed in performance of both materials, although retention of the Z250 restorations was below the minimum specified in the ADA Acceptance Program for Dentin and Enamel Adhesives. Little difference in the restorations' appearance was observed.

Phenotype-genotype correlation in 56 women with nonclassical congenital adrenal hyperplasia due to 21-hydroxylase deficiency.

Complete analysis of the CYP21 gene was performed in 56 unrelated French women with symptomatic nonclassical congenital adrenal hyperplasia. The mutational spectrum and the phenotype-genotype correlation were examined. The overall predominant mutation was V281L, which was present on 51% of alleles and in 80% of women. Three novel mutations were found: L317M, R435C, and a 5'-end gene conversion. Sixty-three percent of the women were carrying a severe mutation of the CYP21 gene, and hence risk giving birth to children with a classical form of the disease. In such cases, screening for heterozygosity in the partner is crucial. Potential genotype/phenotype correlations were examined by classifying the patients into three groups according to the CYP21 allelic combinations: A (mild/mild), B (mild/severe), and C (severe/severe). Primary amenorrhea was more frequent, and mean basal and stimulated 17-hydroxyprogesterone levels were higher in compound heterozygotes for mild and severe mutations (group B) compared with women with two mild mutations (group A), but there was a considerable overlap for individual values. Surprisingly, in two women, a severe mutation was found on both alleles (group C). Therefore, the phenotype cannot be accurately predicted from the genotype. Variability in phenotypic expression may be conditioned by mechanisms other than genetic heterogeneity at the CYP21 locus.

[Ambulatory surgery and oral medicine. 1 years' experience with 795 patients. To assess the quality indicators using precise statistical data and to optimize medical practice]. / Chirurgie ambulatoire et stomatologie. Un an d'activité concernant 795 patients. Asseoir le choix de l'indication sur des connaissances statistiques précises et optimiser la pratique médicale.

The experience of an ambulatory anesthesia and surgery unit was analyzed to assess care and services provided for ambulatory stomatology patients undergoing anesthesia and surgery. Over a 12 month period, 795 patients were evaluated. Patients, practitioners and local communities have been satisfied with the results.

Profiles of plasma serpins in patients with advanced malignant melanoma, gastric cancer and breast cancer.

Blood coagulation and fibrinolysis are activated systemically in patients with malignancy. The precarious balance between coagulation and fibrinolysis is modulated by serine proteinase inhibitors (serpins). Levels of selected serpins (alpha1-antichymotrypsin, alpha1-antitrypsin, alpha2-macroglobulin, antithrombin III, C1 inhibitor, alpha2-antiplasmin), substrates (factor XIIIa, fibrinogen, fibronectin) and endproducts (fibrin/fibrinogen degradation products) of coagulation reactions were measured in the plasma of 61 patients with common malignancies associated with a tendency to thrombosis (i.e. malignant melanoma, gastric cancer and breast cancer). The data revealed a heterogeneity in plasma levels of serpins between tumor types. The most profound differences between cancer and healthy subject groups were found in breast cancer patients. Levels of alpha1-antitrypsin were significantly higher and levels of alpha2-antiplasmin were significantly lower in all cancer groups, whereas there were no differences in antithrombin III levels.

Identification of a YAC spanning the translocation breakpoint t(8;22) associated with acute monocytic leukemia.

Using a series of yeast artificial chromosomes (YAC) from the Bp11-12 chromosome region, we have analyzed a t(8;22) translocation present in two patients suffering from acute leukemia by using fluorescence in situ hybridization (FISH). We have identified a YAC that spans the breakpoint in both cases.

Oncogenic mutations of alpha-Gi2 protein are not determinant for human adrenocortical tumourigenesis.

Activating mutations of G proteins, which are membrane signal transducers, have been associated recently with the development of various endocrine neoplasms. Mutations of two highly conserved codons, Arg201 and Gln227, in the alpha-subunit of the Gs protein, the adenylyl cyclase-stimulating protein, were first described in growth hormone-producing pituitary tumours. They resulted in constitutive activation of the alpha s-subunit by decreasing intrinsic GTPase activity. A similar mutation, affecting codon Arg179 (exon 5) in the alpha-subunit of the Gi2 protein, the adenylyl cyclase-inhibiting protein, has been described by a single group in ovarian and adrenocortical tumours. We evaluated the frequency of activating mutations in the alpha-subunit of the Gi2 protein in 18 human adrenocortical tumours. We screened exons 5 (codon Arg179) and 6 (codon gln205) for mutations by denaturing gradient gel electrophoresis analysis of leucocyte and tumoural DNA. No abnormal migration pattern was found in either exon. The absence of mutation in exon 5, which includes the Arg179 codon, was confirmed in all tumoural DNA by direct sequencing. In conclusion, we did not find any oncogenic mutations in the GTPase domain of the alpha-subunit of the Gi2 protein in adrenocortical tumours. Thus, the previously oncogenic gip2 mutations do not appear to be determinant for adrenocortical tumourigenesis.

Loss of heterozygosity and linkage analysis in breast carcinoma: indication for a putative third susceptibility gene on the short arm of chromosome 8.

We have analysed losses of heterozygosity (LOH) at eight markers from the p12-p22 region of human chromosome 8 in a panel of 113 breast tumors. LOH were detected in almost half of the tumors. The most frequently deleted region included microsatellite (CA)n repeats markers D8S258, D8S133 and D8S259, located at 8p12-p22, while markers NEFL and LPL appeared less frequently altered. In parallel, linkage analysis was performed using the same informative markers, to test for the involvement of chromosome 8p loci in familial breast cancer. Positive cumulative multipoint lod score of 2.51 at theta = 0.0 was obtained with markers NEFL and D8S259. These results suggest that region 8p12-p22 carries at least one tumor suppressor gene involved in sporadic and perhaps also in familial breast cancer.

Characterization of the region of the short arm of chromosome 8 amplified in breast carcinoma.

Chromosomal region 8p11.2-p12 is consistently amplified in human breast cancer. We have constructed a 2.8 Mb YAC contig of this region, centered on the human Fibroblast Growth Factor Receptor 1 (FGFR1) locus and encompassing the Adrenergic beta 3 Receptor (ADRB3) locus. A smaller centromeric YAC contig spanning 1.4 Mb was also assembled, and included the Ankyrin 1 (ANK1) and Tissue-type Plasminogen Activator (PLAT) genes. Results from mapping of the contigs showed physical linkage of the ADRB3 and FGFR1 genes, which were colocalized within the same YAC clone and separated by about 900 kb, FGFR1 being in centromeric position. It also showed physical linkage of ANK1 and PLAT genes, which appear to be separated by a maximum of 700 kb. In parallel, several loci were mapped according to their amplification status in a large panel of breast tumor samples. The overall amplification pattern suggested a continuous amplicon with a core around FGFR1. Data from both the detailed physical map and the amplification status allowed to establish the following gene order, from telomere to centromere: ADRB3-D8S105-FGFR1-ANK1-PLAT-POLB. The precise localization and YAC cloning of the core of the amplicon will allow to isolate a putative oncogene involved in mammary carcinogenesis.