Familial seborrhoeic keratosis associated with multiple 'pure reticulated acanthomas' and infundibulocystic basal cell carcinomas.

BACKGROUND: A variety of genodermatoses with multiple cutaneous tumours and germline genetic alterations, such as PTCH1 mutations, have been described. Other cutaneous syndromes have been associated with somatic gene mutations, such as FGFR3 in familial seborrhoeic keratosis. OBJECTIVES: To describe the clinical, dermoscopic and histopathological features of multiple cutaneous lesions, mostly infundibulocystic basal cell carcinomas (ICBCCs) and pure reticulated acanthomas, present in a family affected by familial seborrhoeic keratosis. In addition, we tested for possible germline alterations in FGFR3 and PTCH1. METHODS: Ten members of one family were clinically examined and 92 skin biopsy specimens were evaluated. Blood samples from six individuals were analysed for FGFR3 and PTCH1 germline alterations. We reviewed the literature concerning genetic FGFR3 alterations in seborrhoeic keratosis. RESULTS: Individuals of all generations affected by familial seborrhoeic keratosis also presented other skin tumours that corresponded histologically to reticulated acanthomas without apocrine or sebaceous differentiation, as well as ICBCCs. In addition, two novel germline variants, p.Pro449Ser (c.1345C>T) in FGFR3 and p.Pro725Ser (c.2173C>T) in exon 14 of PTCH1 were identified in five participants. CONCLUSIONS: We characterize for the first time the clinical, dermoscopic and histopathological features of multiple reticulated acanthomas without apocrine or sebaceous differentiation, for which we propose the term 'pure reticulated acanthoma', and ICBCCs associated with familial seborrhoeic keratosis. We identified FGFR3 and PTCH1 germline polymorphisms whose influence in the development of reticulated acanthomas is unknown.

Circulating mononuclear cells nuclear factor-kappa B activity, plasma xanthine oxidase, and low grade inflammatory markers in adult patients with familial hypercholesterolaemia.

BACKGROUND: Few data are available on circulating mononuclear cells nuclear factor-kappa B (NF-kB) activity and plasma xanthine oxidase (XO) activity in heterozygous familial hypercholesterolaemia (FH). The goal of the study was to analyse circulating mononuclear cells NF-kB and plasma XO activities in FH patients. MATERIALS AND METHODS: Thirty FH index patients and 30 normoglycaemic normocholesterolaemic controls matched by age, gender, body mass index, abdominal circumference and homeostasis model assessment index were studied. Plasma XO and inflammatory markers were measured by standard methods. NF-kB was assayed in circulating mononuclear cells. RESULTS: Familial hypercholesterolaemia patients showed a significantly higher NF-kB (75.0 +/- 20.7 vs. 42.7 +/- 16.8 relative luminiscence units) and XO (0.44 +/- 0.13 vs. 0.32 +/- 0.09 mU mL(-1)) activities than controls. In addition, interleukin-1, interleukin-6, high sensitivity C reactive protein (hsCRP) and oxidized LDL (LDL-ox) were also significantly higher in FH patients. In the total group (FH and controls), XO was significantly associated with LDL-cholesterol (LDL-C), apolipoprotein B (apoB), NF-kB and hsCPR, and NF-kB activity was significantly associated with XO, hsCPR, LDL-ox, LDL-C and apoB plasma values. Using multiple regression analysis, XO was independently associated with hsCPR and NF-kB, and NF-kB activity in circulating mononuclear cells was independently associated with apoB and LDL-ox plasma values. CONCLUSION: Familial hypercholesterolaemia patients show increased activities of NF-kB and XO, and higher values of low grade inflammatory markers related to atherosclerosis. NF-kB activity was independently associated with apoB plasma values. These data could explain in part the high cardiovascular disease risk present in these patients.

Evaluation of E-beam irradiation and storage time in pork exudates using NMR metabolomics.

Seventy-two exudates from pork tenderloin samples, subjected to E-beam irradiation treatments, have been employed to monitor, through 1H NMR analysis, the effects of irradiation dose (0, 1, 2 and 6 kGy) and storage time (1, 6 and 12 days). As far as we know, this is the first study where meat exudate is employed to monitor the effects of irradiation dose and storage time. The 1H NMR spectra, obtained after ~ 2 min, allowed to determine the main components of the pork exudate. Results show that 1H NMR-based metabolomics provides valuable information about the metabolic changes suffered during storage and how these transformations could be affected by E-beam irradiation treatment. The ease to obtain exudates, the simple NMR sample preparation, the good correlation between the selected metabolites, the irradiation treatment and the storage times point to that this study could be the first step to develop a new method for analysis and control of meat conservation and to evaluate its irradiation treatment.

Use of MRI as a predictive tool for physicochemical and rheologycal features during cured ham manufacturing.

Magnetic resonance imaging (MRI) was used to study the structural changes during dry-cured ham manufacturing. T1, T2 and apparent diffusion coefficient (ADC) were determined. Dry cured hams were analysed at different steps of the manufacturing process (raw, salted, post salted, half-cured and cured). Structural changes were linked with the rheological behaviour, estimated by texture profile analysis (TPA) performed in three different muscles of hams (semimembranosus, semitendinosus and biceps femoris). A decrease for T1, T2 and ADC parameters during the curing process was observed, connected to the dehydration kinetics and salt diffusion. Curing process increased hardness and chewiness and reduced elasticity and cohesiveness. Mathematical models were defined to obtain useful equations to monitor ripening. Multiple and simple linear regression models were performed to predict water and salt content and rheological features evolution through MRI parameters. Best settings were achieved with water and salt content for the three studied muscles (R2 around 0.90). T1, T2 and ADC showed a negative correlation with hardness and a positive relation with springiness and cohesiveness.

[Update in Infectious Diseases 2016]. / Actualización en Patología Infecciosa 2016.

Antimicrobial resistance increases it health, social and economic impact. in all areas (state, regional and local), initiatives to try to contain the problem of resistance arise. In the update of this year 2016, we study microbiological, epidemiological and clinical aspects of multi-resistant bacteria, as well as resources for therapeutic approach, from ancient to modern drugs from therapeutic combinations to optimization Stewardship programs. In the case of fungal infection, we analyze clinical scenarios with different species in yeast or new clinical settings in filamentous fungi. Taking paediatric population, homologies and differences with adults in invasive fungal infection were compared. Finally in the field of parasitology, treatment of severe malaria imported or that resistant to antimalarial drugs were reviewed.

Molecular genetics of familial hypercholesterolemia in Spain: Ten novel LDLR mutations and population analysis.

Mutations underlying FH in Spain are largely unknown because only a few and limited surveys have been carried out on Spanish FH patients up to now. To gain information on this issue, we have analysed a group of 113 unrelated Spanish FH patients from an eastern area of Spain (Valencian Community). We have screened the LDLR gene by Southern blot and PCR-SSCP analysis to detect large rearrangements and small mutations, respectively. In addition, we have screened the Apo B gene for mutations known to cause FDB by PCR-SSCP analysis. We have identified a total of 47 different mutations in the LDLR gene (5 large rearrangements, and 42 small mutations, which were characterized by DNA sequencing), 19 of which have not been described in other populations (Valencia-1 to -4, 112insA, P160R, 790DelATGA, 920insTCAG, G642E, and the ten novel mutations E246A, 884delT, I289T, S305F, Q328X, Y354C, I603del, 2312-3C>A, V779M, and N804K). Three of these mutations (15%) were present in more than 1 proband, being mutation 112insA the most prevalent (frequency approximately 8%) in our sample. The Apo B gene R3500Q mutation was found in only one patient and no underlying defect was found in about 27% of patients. Our data support the notion that Spaniards represent a heterogeneous population with its own spectrum of LDLR gene mutations and that, in our population, FDB has a lower frequency or a milder expression than in central Europe countries.

Genetic diagnosis of familial hypercholesterolemia in a South European outbreed population: influence of low-density lipoprotein (LDL) receptor gene mutations on treatment response to simvastatin in total, LDL, and high-density lipoprotein cholesterol.

The aims of this study were to examine the presence of mutations in the low-density lipoprotein receptor gene among subjects clinically diagnosed with familial hypercholesterolemia and to analyze whether the molecular diagnosis helps to predict the response to simvastatin treatment in our familial hypercholesterolemia population. Fifty-five probands and 128 related subjects with familial hypercholesterolemia were studied. Genetic diagnosis was carried out following a three-step protocol based on Southern blot and PCR-single strand conformational polymorphism analysis. A randomized clinical trial with simvastatin was conducted in 42 genetically diagnosed subjects with familial hypercholesterolemia classified as carriers of null mutations (n = 22) and of defective mutations (n = 20). A mutation-causing familial hypercholesterolemia was identified in 46 probands (84%). In 41 of them (89%), a total of 28 point mutations were detected, 13 of which have not been previously described. The remaining five probands (11%) were carriers of large rearrangements. Familial hypercholesterolemia with null mutations showed a poor response to simvastatin treatment. The mean percentage reduction of plasma total and low-density lipoprotein cholesterol levels in these subjects were significantly lower (24.8 +/- 10.3 vs. 34.8 +/- 10.9, P = 0.04 and 30.0 +/- 39.8 vs. 46.1 +/- 18.2, P = 0.02, respectively) than in subjects with defective mutations. Baseline and posttreatment high-density lipoprotein cholesterol plasma values were significantly lower in subjects with familial hypercholesterolemia with null mutations (P < 0.001). In an outbreed Caucasian population, a three-step protocol for genetic screening detected a mutation in the low-density lipoprotein receptor gene in a high percentage (84%) of subjects with familial hypercholesterolemia. Subjects with familial hypercholesterolemia with null mutations (class I) showed lower plasma high-density lipoprotein cholesterol values and a poor low-density lipoprotein cholesterol response to simvastatin treatment.

[Influence of FH Valencia 1 and 2 mutations of the LDL receptor gene on the response to simvastatin in subjects with molecularly defined heterozygous familial hypercholesterolemia in Spain]. / Influencia de las mutaciones HF Valencia 1 y 2 del gen del receptor de LDL sobre la respuesta terapéutica a simvastatina en sujetos con hipercolesterolemia familiar heterocigota caracterizada molecularmente.

BACKGROUND: To analyse whether the molecular diagnosis in FH patients is useful to predict the response to treatment with simvastatin in a south European population. SUBJECTS AND METHOD: A randomised clinical trial with no control group, with 20 mg/day of simvastatin was conducted in 27 genetically diagnosed FH subjects (11 male) from 8 FH families, randomly selected from 30 FH families with a molecular diagnosis. Clinical features and lipid parameters at baseline and after simvastatin treatment were compared between subjects classified as null mutations (FH Valencia 1 and 2; n = 11) and defective mutations (n = 16). RESULTS: FH with null mutations (FH Valencia 1 and 2) have a poor response to simvastatin treatment. The mean reduction of plasma LDLc levels in subjects with null mutations were significantly lower (32.6% [9.5] vs 42.8% [12.2]; p = 0.03) than in subjects with defective mutations. Baseline and after treatment plasma HDLc values were also significantly lower in FH group with null mutations. No statistically significant differences were found at baseline, after treatment and in the response to treatment between males and females. CONCLUSIONS: FH subjects with null alleles (FH Valencia 1 and 2) showed a poor response to simvastatin treatment. The type of LDL receptor gene mutation could predict the response to simvastatin in our south European FH population.

Gitelman syndrome due to p.A204T mutation in CLCNKB gene.

A 45-year-old woman presented with phenotypical features suggestive of Gitelman syndrome (adult age at diagnosis, normal-low blood pressure, hypokalaemia, metabolic alkalosis, hypomagnesaemia, and hypocalciuria). Mutational analysis revealed no significant abnormality in SLC12A3 gene, but homozygous p.A204T mutation was found in the CLCNKB gene. This is a founder effect mutation described in Spanish patients with classic and atypical Bartter syndrome. This report confirms previous descriptions and expands the clinical spectrum of this mutation.

[Effect of gender and obesity on postprandial lipemia in non-diabetic normolipidemic subjects and subjects with familial combined hyperlipidemia]. / Efecto del género y de la obesidad en la lipemia posprandial en sujetos sanos normolipidémicos no diabéticos y sujetos con hiperlipemia familiar combinada.

INTRODUCTION: A new method based on self-measurement of diurnal capillary triglycerides (TG) facilitates the study of postprandial lipemia (PL). The objectives of our study are: to evaluate the effect of gender and obesity on PL measured by self-determination of diurnal capillary TG with Accutrend GCT in normolipidemic non-diabetic subjects and subjects with familial combined hyperlipidemia (FCH). MATERIAL AND METHODS: We studied 23 FCH subjects (10 males) and 45 normolipidemic non-diabetic subjects (29 males). All subjects self-determine 3 diurnal capillary TG profiles during a week. RESULTS: In normolipidemic non diabetic subjects significantly higher diurnal TG profiles and area under the curve of TG (AUCTGc) (25.25 +/-9.09 vs 19.71 +/- 6.16 mmolh/l) were found in males compared to females. In FCH subjects these differences were not found and the AUCTGc correlated with BMI (r = 0.510, p < 0.05) and waist circumference (r = 0.453, p < 0.05). Obese subjects (BMI >or= 27 kg/m2) showed diurnal TG profiles and AUCTGc significantly higher than the non-obese. DISCUSSION: Normolipidemic non diabetic females showed a lower PL compared to males, probably due to the effect of estrogens in PL metabolism. Obesity negatively influences PL in normolipidemic non diabetic subjects and subjects with FCH.