Characterization of femtosecond laser written waveguides for integrated biochemical sensing

Fluorescence detection is known to be one of the most sensitive among the different optical sensing techniques. This work focuses on excitation and detection of fluorescence emitted by DNA strands labeled with fluorescent dye molecules that can be excited at a specific wavelength. Excitation occurs via optical channel waveguides written with femtosecond laser pulses applied coplanar with a microfluidic channel on a glass chip. The waveguides are optically characterized in order to facilitate the design of sensing structures which can be applied for monitoring the spatial separation of biochemical\ud species as a result of capillary electrophoresis

Integration of femtosecond laser written waveguides for optical detection in microfluidic chips

Optical waveguides have been fabricated focusing femtosecond laser pulses into a commercial microfluidic chip. The waveguides intersect the channels and are used to optically excite their content. Fluorescence from the optically addressed volume is efficiently collected by a fiber, resulting in an highly compact and portable setup

A recessive homozygous p.Asp92Gly SDHD mutation causes prenatal cardiomyopathy and a severe mitochondrial complex II deficiency

Succinate dehydrogenase (SDH) is a crucial metabolic enzyme complex that is involved in ATP production, playing roles in both the tricarboxylic cycle and the mitochondrial respiratory chain (complex II). Isolated complex II deficiency is one of the rarest oxidative phosphorylation disorders with mutations described in three structural subunits and one of the assembly factors; just one case is attributed to recessively inherited SDHD mutations. We report the pathological, biochemical, histochemical and molecular genetic investigations of a male neonate who had left ventricular hypertrophy detected on antenatal scan and died on day one of life. Subsequent postmortem examination confirmed hypertrophic cardiomyopathy with left ventricular non-compaction. Biochemical analysis of his skeletal muscle biopsy revealed evidence of a severe isolated complex II deficiency and candidate gene sequencing revealed a novel homozygous c.275A>G, p.(Asp92Gly) SDHD mutation which was shown to be recessively inherited through segregation studies. The affected amino acid has been reported as a Dutch founder mutation p.(Asp92Tyr) in families with hereditary head and neck paraganglioma. By introducing both mutations into Saccharomyces cerevisiae, we were able to confirm that the p.(Asp92Gly) mutation causes a more severe oxidative growth phenotype than the p.(Asp92Tyr) mutant, and provides functional evidence to support the pathogenicity of the patient’s SDHD mutation. This is only the second case of mitochondrial complex II deficiency due to inherited SDHD mutations and highlights the importance of sequencing all SDH genes in patients with biochemical and histochemical evidence of isolated mitochondrial complex II deficiency

Formation mechanism of non-metallic inclusions in different stainless steel grades

In this study the processing routes of three different stainless steel grades were followed; during the reducing period in the AOD plant samplings of steel and slag and measurements of temperature and oxygen activities were performed. The goal was to develop tools for the improvement in the comprehension about the development of the non metallic inclusions in stainless steels. The inclusions in the steel samples were analysed by means of a SEM and then the evaluation of the oxide activities and phases present within them was performed with Thermocalc©. A model developed by Janke and co-workers was implemented in order to compute the activity of elements in the liquid steel. This is based on Wagner's formalism but it is more accurate for the steel baths where solutes are not at infinite dilution. This is the reason why Janke's formalism is better than the Wagner's one in the study of stainless steels, as they are high-alloy steels. It was found that Janke's formalism lacks reliability, when it neglects some strong interactions between two elements (e.g. O and another element having high affinity to oxygen).The activities of oxides at the equilibrium with the liquid metal were calculated and compared to those obtained from the Thermocalc©-based analysis of inclusions. From this comparison some hypotheses were made about the nucleation and modification of SiO 2 , Al 2 O 3 and Cr 2 O 3 . By making some variations to the model for the calculations of the oxides activity at the equilibrium with the steel bath, it has been also assessed how the model results are influenced by the choice of some thermodynamic parameters such as the interactions coefficients and the equilibrium constants

Wernicke's encephalopathy in a malnourished surgical patient: clinical features and magnetic resonance imaging.

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Postite lichenoide mastocitaria

A 59 years-old man presented a single erythematous patch, with a cord-like infiltrated upper margin for one year localized to the coronal sulcus and prepuce mucosa of his penis. The patient was in good general health and had not used any kind of systemic or topical drugs for the past three months. Microbiologic laboratory study of the lesion excluded presence of Candida species. The histopathologic findings from a 4 mm punch biopsy were characterized by a band-like infiltrate, obscuring the dermo-epidermal junction. The infiltrate was made of a prevalence of mastocytes (toluidine blue and Giemsa stains) and lymphocytes. The case was provisionally defined «Lichenoid posthitis with mast cell». Histopathologically, there are only a few lichenoid dermatitides which involve the penis, i.e. lichen planus, lichen planus-like drug eruption, lichenoid lupus erithematosus. The prevalence of mastocytes is unusual and excludes a diagnosis of lichen planus, lichen planus-like drug eruption and lichenoid lupus erithematosus. Although the infiltrate in our case was lichenoid and some necrotic keratinocytes were present, like in true lichen planus, the infiltrate contained several mastocytes. The absence of plasma cells and of eosinophils excluded both a diagnosis of balanitis circumscripta plasmacellularis and a lichen planus-like drug eruption. The tentative explanation for the massive presence of mastocytes in this lichenoid infiltrate remains a matter of speculation

TRAFFIC NOISE EXPOSURE AND OCCURRENCE OF MYOCARDIAL INFARCTION IN PISA (ITALY).

Introduction: Several studies have suggested a relationship between traffic noise and ischemic heart Disease, in particular acute myocardial infarction (MI). Objectives: To analyse the association between residential exposure to road traffic noise and MI incidence in Pisa, Italy. Methods: Incidence of first MI in the period 2002-2006 was obtained from mortality and hospitalization data (1998-2006). Residential address and geographical coordinates was available for each subjects together with age and gender data. Traffic noise exposure was estimated at the buildings façades of the house of each subjects from the 3D noise maps of Pisa. The exposure estimates were done by Environmental Protection Agency of Tuscany Region according to the new acoustic indicators and interim methods issued by European Directive 2009/49/CE. Results: 823 MI cases were identified in 2002-2006 (480 males) among 12,710 residents (5774 males) living in 1,296 different buildings. Incidence rates were computed by sex, age groups (30-49;50-69;70+ years) and nocturnal noise levels (55Db). MI incidence rates were higher among males living in building with high level of nocturnal traffic noise exopure (=>55Db): the rate ratio between high/low noise levels was 1.08 at age 30-49, 1.19 at age 50-69, 1.35 over 70 years . Among women MI incidence rates were about 50% lower than those of male and with similar trend by age. Conclusions: This preliminary results support the presence of an association between occurrence of first myocardial infarction and high leves of nocturnal traffic noise exposure at the place of residence. Further analyses should consider the residence duration and the possibility of confounding from air pollution exposure and socioeconomic statu

Use of a Caco-2 cell culture model for the characterization of intestinal absorption of antibiotics

The use of cell culture models, based on human cell lines derived from the intestinal epithelium, is a promising new tool for the in vitro study of oral absorption of drugs. An assay has been developed using the Caco-2 cell line with the aim of studying the in vitro permeability of antibiotics. The reproducibility of the assay conditions have been assessed by means of the transport of two different marker molecules: 3H-mannitol and fluorescein, and transepithelial electrical resistance (TEER) value for cells monolayers. The results show that cells after 21 days of culture give significantly tighter monolayers than those after 15 days with higher reproducibility. Apparent permeability coefficients (Papp) have been measured for 13 antibiotics, known to be absorbed at different rates in humans. Papp values span from 0.18 x 10(-6) cm/s for cephaloridine to 5.79 x 10(-6) cm/s for rifampicin where the corresponding bioavailability values, known from literature, span from < 3 to 98%. A Caco-2 in vitro model appears to be suitable to investigate the transport of drugs across the intestinal epithelium. This model gives no information about the metabolic phase that follows the absorption of a drug but could provide information to investigate its pharmacokinetical behavior

Muco-cutaneous changes during long-term therapy with hydroxyurea in chronic myeloid leukaemia.

Hydroxyurea is an antimetabolite agent used in the treatment of myeloproliferative disorders and sickle cell anaemia. Although hydroxyurea is relatively well tolerated, adverse effects often involve skin and mucous membrane during long-term therapy. A group of 510 patients affected by chronic myeloid leukaemia from 1977 to 1998 has been considered. Only 158 patients were treated with hydroxyurea and fulfilled inclusion/exclusion criteria of this study. A spectrum of severe cutaneous and mucosal changes (inflammatory and neoplastic) was seen in about 13% of patients (21 patients out of 158) and was studied in detail. Cutaneous and mucosal atrophy were observed in all 21 patients. Skin atrophy was often characterized by numerous telangiectases, especially on legs and on sun-exposed sites (16/21). Cutaneous, mucosal and nail hyperpigmentation was evident, albeit with variable extent, in 10 of the 21 patients. Severe stomatitis and glossitis with flattening of papillae were another common finding. Five patients, who received a particularly long treatment with hydroxyurea, developed squamous-cell neoplasms on sun-exposed sites (both squamous-cell carcinomas and keratoacanthomas). Acral changes were characteristic and constant, including acral erythema (21/21), dermatomyositis-like changes on the dorsa of hands (7/21), ulcers localized on acral areas of legs, on genitalia and oral mucosae (20/21). The frequency and the variety of these muco-cutaneous changes are reported and the mechanisms by which hydroxyurea may induce this muco-cutaneous syndrome-like group of changes, are proposed