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Objective: To compare the effect of inhaled nitrous oxide (INO) on pain control during in‐office hysteroscopy with 1% lidocaine paracervical infiltration and no analgesic. Design: Single‐blind stratified randomised clinical trial with masked assessment by a third party. Setting: Department of Obstetrics and Gynaecology in a Spanish hospital. Population: Women who underwent hysteroscopy. Methods: Patients were stratified into three groups according to the purpose of the hysteroscopy (biopsy, polypectomy or tubal sterilisation) and then assigned to different treatment groups through a permuted‐blocks randomisation within strata. Pain scale was provided by a gynaecologist totally blinded to procedures and treatments. Effects were assessed using a one‐way analysis of variance following an intention‐to‐treat approach. Main outcome measures: Visual analogue scale (VAS) from 0 to 100 mm. Results: A total of 314 women were included: 105 to INO, 104 to 1% lidocaine and 105 to no analgesic. Baseline characteristics were comparable. Mean VAS score after the procedure was 34.7 ± 25.8 mm, 36.1 ± 22.9 mm (P = 1.0) and 47.3 ± 28.2 mm (P = 0.001) for INO, 1% lidocaine and no analgesic, respectively. No adverse events were reported in 91 (86.7%) patients in the INO group compared with 79 (76%) in the 1%‐lidocaine group (P = 0.04) and 85 (81%) in the no‐analgesic group (P = 0.26). Conclusion: INO was as effective as 1% lidocaine in pain control for in‐office hysteroscopy and was better tolerated. The no‐analgesic group presented the poorer results, so was the least recommended clinical option. [ABSTRACT FROM AUTHOR]

Plant pathogens have developed different strategies during their evolution to infect and colonize their hosts. In the same way, plants have evolved different mechanisms acting against potential pathogens trying to infect and colonize their tissues. Regulation of a wide variety of proteins is required in order to perceive the pathogen and to activate the plant defence mechanisms. The apoplast is the first compartment where these recognition phenomena occur in most plant–pathogen interactions, allowing the exchange of different molecules and facilitating inter‐ and intracellular communication in plant cells. Proteomic analysis of the apoplast in recent years has found the initial biochemical responses involved in pathogen recognition and early defence responses. However, this proteomic approach requires some specific experimental conditions to obtain an extract free of cytoplasmic proteins and nonprotein contaminants that affect the subsequent stages of separation and quantification. Obtaining the highest proportion of proteins from the apoplastic space in infected tissues requires different steps such as extraction of apoplastic washing fluids and preparation of total secreted proteins (protein precipitation, solubilization, separation and digestion). Protein identification using mass spectrometry techniques and bioinformatics tools identifying peptides for the extracellular exportation is required to confirm the apoplastic location. This review compiles the most commonly used techniques for proteomic studies, focusing on the early biochemical changes occurring in the apoplast of plants infected by a wide range of pathogens. The scope of this approach to discover the molecular mechanisms involved in the plant–pathogen interaction is discussed. [ABSTRACT FROM AUTHOR]

Abstract: Analysis of electromyography (EMG) signals is a necessary step in the diagnosis of neuromuscular diseases. Automatic classification systems can assist specialists and optimize the diagnostic process by applying time‐frequency analysis, fuzzy entropy, and neural networks to EMG signals in order to identify the presence of characteristics of a specific disorder, such as myopathy and amyotrophic lateral sclerosis. The performance of a decision support system depends on three important issues: the correct estimation of features from the EMG signal, the proper criteria for relevance analysis, and the learning process of the classification algorithm. In this paper, Discrete Wavelet Transform and Fuzzy Entropy are used to extract and select features from EMG signals, whereas Artificial Neural Networks are used to give the recognition result. The database used in this study is available for public use in EMGLAB, which is a website for sharing data, software, and information related to EMG decomposition. Results using the combination of these techniques show an accuracy around 98% for identifying EMG signals from three classes: healthy, patients with myopathy, or evidence of amyotrophic lateral sclerosis. [ABSTRACT FROM AUTHOR]

Abstract: Background: Recent studies show that most systemic mastocytosis (SM) patients, including indolent SM (ISM) with (ISMs+) and without skin lesions (ISMs−), carry the KIT D816V mutation in PB leukocytes. We investigated the potential association between the degree of involvement of BM hematopoiesis by the KIT D816V mutation and the distribution of different maturation‐associated compartments of bone marrow (BM) and peripheral blood (PB) CD34+ hematopoietic precursors (HPC) in ISM and identified the specific PB cell compartments that carry this mutation. Methods: The distribution of different maturation‐associated subsets of BM and PB CD34+ HPC from 64 newly diagnosed (KIT‐mutated) ISM patients and 14 healthy controls was analyzed by flow cytometry. In 18 patients, distinct FACS‐purified PB cell compartments were also investigated for the KIT mutation. Results: ISM patients showed higher percentages of both BM and PB MC‐committed CD34+ HPC vs controls, particularly among ISM cases with MC‐restricted KIT mutation (ISMMC); this was associated with progressive blockade of maturation of CD34+ HPC to the neutrophil lineage from ISMMC to multilineage KIT‐mutated cases (ISMML). Regarding the frequency of KIT‐mutated cases and cell populations in PB, variable patterns were observed, the percentage of KIT‐mutated PB CD34+ HPC, eosinophils, neutrophils, monocytes and T cells increasing from ISMs−MC and ISMs+MC to ISMML patients. Conclusion: The presence of the KIT D816V mutation in PB of ISM patients is associated with (early) involvement of circulating CD34+ HPC and multiple myeloid cell subpopulations, KIT‐mutated PB CD34+ HPC potentially contributing to early dissemination of the disease. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the environmental fate and behaviour of the biocontrol product based on Pantoea agglomerans CPA-2 cells after its release into the field. Three different methods, dilution plating, quantitative real-time PCR ( qPCR) and propidium monoazide combined with qPCR ( PMA-qPCR) were used to track the CPA-2 population. Populations quantified by qPCR were statistically different compared with those by the PMA-qPCR and dilution plating methods. In addition, the spray dispersion of the CPA-2 treatment was evaluated using water-sensitive papers. A lack of dispersion of the CPA-2 treatment was observed at distances of 2.5 ± 0.5 m. The presence and persistence of CPA-2 in the environment were monitored in different areas, by dilution plating and confirmed by conventional PCR. The results showed that CPA-2 can survive but not proliferate on weed and leaves. The persistence on inert surfaces, such as motorised backpack sprayer, gloves and working clothes, was less than 7 days. In conclusion, PMA-qPCR was a potential tool for fast and specific monitoring of viable populations of CPA-2 and it gave valuable information on population behaviour. Moreover, the results demonstrate that CPA-2 would not present a risk for the environment because of its low establishment, survival and dispersion. [ABSTRACT FROM AUTHOR]

Fatty acyl- Co A reductases ( FARs), the enzymes that catalyse reduction of a fatty acyl- Co A to the corresponding alcohol in insect pheromone biosynthesis, are postulated to play an important role in determining the proportion of each component in the pheromone blend. For the first time, we have isolated and characterized from the Egyptian cotton leaf worm Spodoptera littoralis ( Lepidoptera: Noctuidae) a FAR c DNA ( Slit- FAR1), which appeared to be expressed only in the pheromone gland and was undetectable in other female tissues, such as fat body, ovaries, wings, legs or thorax. The encoded protein has been successfully expressed in a recombinant system, and the recombinant enzyme is able to produce the intermediate fatty acid alcohols of the pheromone biosynthesis of S. littoralis from the corresponding acyl- Co A precursors. The kinetic variables Km and Vmax, which have been calculated for each acyl- Co A pheromone precursor, suggest that in S. littoralis pheromone biosynthesis other biosynthetic enzymes (e.g. desaturases, acetyl transferase) should also contribute to the final ratio of components of the pheromone blend. In a phylogenetic analysis, Slit- FAR1 appeared grouped in a cluster of other FARs involved in the pheromone biosynthesis of other insects, with little or non-specificity for the natural pheromone precursors. [ABSTRACT FROM AUTHOR]

Objectives Nucleoside reverse transcriptase inhibitor ( NRTI)-sparing regimens may be needed in patients with NRTI toxicity. Maraviroc ( MVC) plus ritonavir-boosted darunavir ( DRV-r) or atazanavir is associated with slightly lower response rates than triple therapy in drug-naïve patients. No information is available on these combinations in pretreated patients. The aim of this study was to assess the efficacy and safety of MVC plus DRV/r once-daily (qd) in HIV-infected pretreated patients. Methods A retrospective cohort study including patients starting MVC 150 mg plus DRV/r 800/100 mg qd, with CCR5 tropism and no resistance mutations for DRV/r, was performed. The primary efficacy endpoint was the achievement of plasma HIV RNA < 50 HIV-1 RNA copies/mL after 48 weeks. The frequency of serious adverse effects was investigated. Results Sixty patients were recruited to the study, of whom 48 (80%) had HIV RNA < 50 copies/mL at baseline. Reasons for starting MVC plus DRV/r were: adverse effects in 38 individuals (63%), simplification in 15 (25%) and virological failure in seven (12%). The main analysis (intention to treat, noncompleter = failure) showed that 47 patients (78%) achieved HIV RNA < 50 copies/mL at 48 weeks (paired comparison with baseline, P = 1.0). On-treatment analysis showed that 42 (86%) of 49 patients presented HIV RNA < 50 copies/mL at 48 weeks (paired comparison with baseline, P = 1.0). Median (interquartile range) CD4 cell counts increased from 491 (301−729) to 561 (367−793) cells/μL at 48 weeks ( P = 0.013). Only one patient discontinued therapy because of adverse effects. Conclusions Most individuals starting MVC plus DRV/r qd because of simplification or adverse effects maintained HIV suppression after 48 weeks of follow-up. [ABSTRACT FROM AUTHOR]

In the tropic, the small-scale pork production is negatively influenced by the low availability of high protein ingredients. The study aimed to compare the protein and starch hydrolysis as well as fibre fermentation of five tropical legume grains ( Canavalia brasiliensis, CB; Lablab purpureus, LP; Vigna unguiculata, white WVU; pink PVU and red RVU) and a control (extruded full-fat soybean (SB)), using an in vitro model that simulated digestion in the gastrointestinal tract of pigs. A sequential in vitro hydrolysis was carried out with pepsin (120 min) and pancreatin (240 min) to determine the degree of hydrolysis (DH) of protein and starch. The indigestible residue was fermented in vitro with pig faecal inoculum to compare the modelled kinetics of gas production over 72 h and the production of short-chain fatty acids (SCFA). After 360 min of pepsin-pancreatin hydrolysis, SB and WVU had the highest protein hydrolysis (76% and 66%) and PVU and WVU the highest starch hydrolysis (70% and 64%) (p < 0.01). The in vitro fermentation of the indigestible residue of WVU resulted in the highest (482 ml/g DM; p < 0.001) and CB the lowest (335 ml/g DM) gas production. These data were consistent with the SCFA production. Butyrate, propionate and total SCFA were higher (or tended) for RVU and WVU when compared with CB and SB (p = 0.015-0.085). In conclusion, the high DH of protein and starch as well as the high gas and SCFA production obtained with raw WVU makes it an interesting alternative to SB as a feedstuff for swine nutrition in the tropic. Other legume grains (LP and CB) cannot be used by pigs in their raw form. [ABSTRACT FROM AUTHOR]

Background: The incidence of unilateral retinoblastoma varies globally, suggesting possible environmental contributors to disease incidence. Maternal intake of naturally occurring folate from vegetables during pregnancy is associated inversely with the risk of retinoblastoma in offspring.Methods: The authors used a case-control study design to examine the association between retinoblastoma risk and maternal variations in the folate-metabolizing genes methylenetetrahydrofolate reductase (MTHFR) (a cytosine-to-thymine substitution at nucleotide 677 [MTHFR677C→T]; reference single nucleotide polymorphism rs1801133) and dihydrofolate reductase (DHFR) (a 19-base-pair deletion of intron 1a [DHFR19bpdel]; rs70991108). In central Mexico, 103 mothers of children with newly diagnosed unilateral retinoblastoma were enrolled in an institutional review board-approved study along with a control group of 97 mothers who had healthy children. Mothers were interviewed regarding perinatal characteristics, including use of prenatal vitamin supplements, and gave peripheral blood samples, which were used for polymerase chain reaction-based genotyping of rs1801133 and rs70991108.Results: The risk of having a child with unilateral retinoblastoma was associated with maternal homozygosity for DHFR19bpdel (odds ratio, 3.78; 95% confidence interval, 1.89-7.55; P = .0002), even after controlling for the child's DHFR19bpdel genotype (odds ratio, 2.81; 95% confidence interval, 1.32-5.99; P = .0073). In a subgroup of 167 mothers with data on prenatal intake of supplements containing folic acid (a synthetic form of folate), DHFR19bpdel-associated risk was elevated significantly only among those who reported taking folic acid supplements. Maternal MTHFR genotype was unrelated to the risk of having a child with retinoblastoma.Conclusions: Maternal homozygosity for a polymorphism in the DHFR gene necessary for converting synthetic folic acid into biologic folate was associated with an increased risk for retinoblastoma. Prenatal ingestion of synthetic folic acid supplements may be associated with increased risk for early childhood carcinogenesis in a genetically susceptible subset of the population. [ABSTRACT FROM AUTHOR]

Knowledge of the socio-demographic distribution of eating behaviours can aid our understanding of their contribution to the obesity epidemic and help to address healthy eating interventions to those who can benefit most. This cross-sectional study assessed the frequency of self-reported eating behaviours among 11,603 individuals representative of the non-institutionalized Spanish population aged ≥18 years in the period 2008-2010. In the adult population of Spain, 24.3% had lunch and 18.2% had dinner away from home >3 times per month. About three-fourths of adults did not plan the amount of food to be eaten, and did not choose light foods and/or skim dairy products. Also, 26% did not trim visible fat from meat, and 74.7% usually ate while watching television. Compared with individuals with primary or less education, those with university studies were more likely to remove fat from meat (age- and sex-adjusted odds ratio [aOR] 1.25; 95% confidence interval [CI] 1.08-1.44), and to choose light food and/or skim dairy (aOR 1.50; 95% CI 1.30-1.77), and less likely to eat while watching television (aOR 0.54; 95% CI 0.47-0.63). In conclusion, the prevalence of several obesity-related eating behaviours is high in Spain, which indicates a deficient implementation of dietary guidelines. Socioeconomic inequalities in eating behaviours should also be addressed. [ABSTRACT FROM AUTHOR]

Mastocytosis comprises a heterogeneous group of disorders characterized by the presence of clonal mast cells (MC) in organs such as skin, bone marrow (BM), and gastrointestinal tract, among other tissues. The clonal nature of the disease can be established in most adult patients by the demonstration of activating KIT mutations in their BM MC. When highly sensitive techniques capable of identifying cells present at very low frequencies in a sample are applied, BM MC from virtually all systemic mastocytosis patients display unique immunophenotypical features, particularly the aberrant expression of CD25. By contrast, large, multifocal BM MC aggregates (the only World Health Organization major criterion for systemic mastocytosis) are absent in a significant proportion of patients fulfilling at least three minor criteria for systemic mastocytosis, particularly in subjects studied at early stages of the disease with very low MC burden. Moreover, recent molecular and immunophenotypical investigations of BM MC from patients with indolent systemic mastocytosis have revealed a close association of some biological features (e.g., multilineage involvement of hematopoiesis by the KIT mutation and an immature mast cell immunophenotype) with an increased risk for disease progression. These observations support the fact that, although the current consensus diagnostic criteria for systemic mastocytosis have been a major advance for the diagnosis and classification of the disease, rationale usage of the most sensitive diagnostic techniques available nowadays is needed to improve the diagnosis, refine the classification, and reach objective prognostic stratification of adult mastocytosis. [ABSTRACT FROM AUTHOR]

Background Despite the good prognosis of pediatric mastocytosis, some patients suffer from severe mast cell ( MC) mediator-associated symptoms. The aim of this study was to identify predictors for severe MC mediator release symptoms in children with mastocytosis in the skin ( MIS). Methods Serum baseline total tryptase (sb T) levels in 111 children with MIS - 80 maculopapular cutaneous mastocytosis/plaque mastocytosis, 22 nodular mastocytosis, and nine diffuse cutaneous mastocytosis - were investigated as a predictive biomarker for the occurrence of MC mediator-related signs and symptoms within the first 18 months after disease onset. Results Twelve children (11%) who showed extensive cutaneous disease involving >90% of body surface area ( BSA) suffered from severe symptoms requiring hospitalization, with ( n = 5) or without ( n = 6) management in the intensive care unit ( ICU) owing to life-threatening complications. The median sbT was significantly ( P < 0.001) higher in patients with extensive cutaneous disease vs those with <90% of BSA involved (45.5 vs 5.2 μg/l, respectively), as well as in children with grade 4 (severe mastocytosis-related symptoms requiring emergency therapy and hospitalization) vs those with grade <4 (46.2 vs 5.2 μg/l, respectively). Receiver operating characteristics curve analyses showed that the optimal cutoff s for sbT to predict the need for daily antimediator therapy, hospitalization, and the management in an ICU were 6.6, 15.5, and 30.8 μg/l, respectively (sensitivity and specificity of 77% and 79%, 100% and 95%, and 100% and 96%, respectively). Conclusions Increased sb T in association with extensive cutaneous involvement identifies patients at risk for severe MC activation events in pediatric mastocytosis. [ABSTRACT FROM AUTHOR]

Summary This is the first study to report the prevalence of general obesity and abdominal obesity (AO) in the adult population of Spain based on measurements of weight, height and waist circumference. The data are taken from the ENRICA study, a cross-sectional study carried out between June 2008 and October 2010 in 12,883 individuals representative of the non-institutionalized population on Spain aged 18 years and older. Anthropometry was performed under standardized conditions in the households by trained interviewers. Overweight was considered as body mass index (BMI) 25-29.9 kg m−2, and obesity as BMI ≥ 30 kg m−2. AO was defined as waist circumference >102 cm in men and >88 cm in women. The prevalence of obesity was 22.9% (24.4% in men and 21.4% in women). About 36% of adults had AO (32% of men and 39% of women). The frequency of obesity and of AO increased with age and affected, respectively, 35 and 62% of persons aged 65 and over. The frequency of obesity and AO decreased with increasing educational level. For example, 29% of women with primary education or less had obesity vs. only 11% of those with university studies. The prevalence of obesity was very high in the Canary Islands and in the south of Spain. [ABSTRACT FROM AUTHOR]

In this study, several neuropeptides were identified by immunohistochemistry in neuroendocrine cells (NEC) located in the gut epithelium and nerve cell bodies of the enteric nervous system of pejerrey Odontesthes bonariensis, a species that is a promising candidate for intensive aquaculture. The neuropeptides involved in orexigenic or anorexigenic action, i.e. gastrin, cholecystokinin-8, neuropeptide Y and calcitonin gene-related peptide (CGRP), displayed a significantly higher number of immunoreactive NECs in the anterior intestine, suggesting that this region of the gut plays an important role in the peripheral control of food intake. On the other hand, leu-enkephalin and vasoactive intestinal peptide (VIP), both associated with the modulation of the enteric immune system, showed no significant variations in the mean value of immunopositive NECs between the anterior and posterior intestine. This may indicate that their activity is required at a similar level along the entire gut. In addition, CGRP and VIP-immunoreactive neurons and nerve fibres were observed in the myenteric plexus, which might exert synergistic effects with the neuropeptides immunolocalized in NECs. [ABSTRACT FROM AUTHOR]

Background: Hip fracture surgery is associated with high post-operative mortality and poor functional results: the excess mortality is 20% in the first year; of those patients who survive, only 50% recover their previous ability to walk. The purpose of this study was to assess the predictive value of six functional status and/or surgical risk scoring systems with regard to serious complications after hip fracture surgery in the elderly. Methods: We performed a prospective study of a consecutive series of 232 patients (aged 65 years or older) undergoing hip fracture surgery. We pre-operatively applied: The American Society of Anesthesiologists classification, the Barthel index, the Goldman index, the Physiological and Operative Severity Score for the enUmeration of Mortality and Morbidity (POSSUM) scoring system, the Charlson index and the Visual Analogue Scale for Risk (RISK-VAS) scale. These scales were evaluated with respect to three variables: incidence of serious complications, the ability to walk after a 3-month period and 90-day survival. The predictive value of the different scales was assessed by the calculated area under a receiver operating characteristic curve. Results: The RISK-VAS scale, the POSSUM scoring system and the Charlson index reached a sufficient predictive value with regard to serious post-operative complications. The Barthel index and the RISK-VAS scale were those most useful for predicting ambulation at 3 months. None of the scales proved to be capable of predicting 90-day mortality. Conclusions: A simple index such as the RISK-VAS scale was the best predictor of serious post-operative complications. The functional level before the fracture, measured with the Barthel index, had a major influence on the ambulation recovery. [ABSTRACT FROM AUTHOR]

Objective Turner syndrome (TS) is an indication for GH therapy in spite of the modest growth response. Somatic growth depends not only on GH insulin-like growth factor I (IGF-I) axis but also on thyroid hormone (TH) status. We have previously reported that supraphysiological IGF-I levels diminished TH actions in rat tissues by reducing the nuclear TH receptor (TR). GH treatment to TS patients induces high IGF-I levels and therefore a reduction of TH action in tissues may be expected. We aimed at evaluating the effect of GH therapy in TS girls on peripheral TH action. Design and patients We set up a reverse transcription-polymerase chain reaction (RT-PCR) for TR mRNA estimation in peripheral blood mononuclear cells (PBMC) and compared TR mRNA levels from 10 normal, 10 TS and 10 TS girls under GH therapy (0·33 mg/kg/week for 0·5–2 years). Measurements After RNA extraction from PBMC, TR and β-actin mRNAs were coamplified by RT-PCR. In addition serum biochemical markers of TH action were measured: thyrotropin (TSH), sex hormone binding globulin (SHBG), osteocalcin (OC), β-crosslaps (β-CL), iodothyronines by electrochemiluminescency and IGF-I by immunoradiometric assay (IRMA) with extraction. Results TR mRNAs from PBMC were reduced in TS patients under GH treatment. In turn, serum TSH, OC, β-CL and IGF-I were increased while SHBG was reduced by GH treatment in TS patients. Conclusions GH treatment reduced TR expression in PBMC and biochemical serum markers of TH action. These results suggest that GH treatment in TS patients impair peripheral TH action at tissue level and prompt a role in the reduced growth response to the therapy. [ABSTRACT FROM AUTHOR]

Background Mast cells (MCs) play a key role in allergic diseases through the release of inflammatory mediators, which are responsible of allergic symptoms. Mastocytosis is characterized by an abnormal proliferation and accumulation of mast cells, in which mediators are released intermittingly or continuously. Despite these clinical similarities, few studies have addressed the presence of allergic symptoms in mastocytosis patients, including anaphylaxis. Objective A prospective evaluation was carried out to study the prevalence of allergic diseases in patients with mastocytosis and their impact on the natural history of mastocytosis. Methods A questionnaire was given to 210 patients with mastocytosis to evaluate the history of asthma, rhinitis, conjunctivitis, atopic dermatitis, urticaria and anaphylaxis. Patients underwent total IgE, Phadiatop® infant (aeroallergens and food allergens), specific IgE to latex and to Anisakis simplex determinations. Skin tests were done to 72 patients. Results The prevalence of allergy, as defined by clinical symptoms associated to specific IgE, was 23.9%. Total IgE level was significantly higher in patients with allergy as compared with patients without allergy (median 58 vs. 16.5 kU/L, P<0.0001). Anaphylactic symptoms were present in 36 patients (22%), in nine the allergen was identified. Males had more allergy and anaphylactic symptoms than females (61.5% vs. 38.5% and 72% vs. 28%, respectively). Conclusions Allergic diseases coexist in patients with mastocytosis with similar frequency as compared with the general population. Anaphylactic symptoms are more prevalent in males with mastocytosis and in patients with elevated IgE. Capsule summary The prevalence of allergy in mastocytosis is similar to the general population. Anaphylactic symptoms are more prevalent in males and in patients with elevated IgE. The coexistence of atopy does not influence mastocytosis-associated symptoms. [ABSTRACT FROM AUTHOR]

Tepary bean (Phaseolus acutifolius A. Gray), a low-rainfall crop from the Sonoran desert, is thought to have low diversity; however, its relationship to its wild relatives is poorly understood. In this study, a total of 147 accessions were evaluated by means of AFLP markers to (i) establish the taxonomic relationships within and between the Acutifolii and other sections and (ii) to understand tepary bean domestication. The structure among the 10 species analyzed corresponded to currently recognized sections: Phaseolus glabelus and Phaseolus lunatus L. were equally distant from the phaseoli and coccinei sections and the rugosi section included Phaseolus angustissimus, Phaseolus carteri and Phaseolus filiformis. We also compared the gene pool differences for common (Phaseolus vulgaris L.) and lima bean (P. lunatus) with differences observed within the Acutifolii section. The wild relative, Phaseolus parvifolius persistently separated from the bulk of both cultivated and wild tepary, validating its status as a separate species; while within the wild accessions, there was no obvious grouping along the foliar variants. On the basis of our results, one of two Mexican states, Sinaloa or Jalisco, could have been the domestication center, although the hypothesis of multiple domestication events cannot be discarded. Furthermore, domesticated tepary bean was most likely derived from wild genotypes of var. acutifolius rather than genotypes of var. tenuifolius. [ABSTRACT FROM AUTHOR]

Dominguez Reyes A, Muñoz Muñoz L, Aznar Martín T. Study of calcium hydroxide apexification in 26 young permanent incisors. Dent Traumatol 2005; 21: 141–145.© Blackwell Munksgaard, 2005.This study was carried out in order to observe the effectiveness of apexification in young permanent incisors. The sample comprised 26 young permanent incisors with necrotic pulp and open apices. The time taken to obtain apical closure, its form and size were analysed in order to find out if closure was influenced by existing pathology or size of apex. The treated teeth were compared with their corresponding contralateral teeth. The test of McNemar andanovawas used and a result ofP = 0.05 was considered significant. Teeth with pretreatment apical shapes that were convergent or parallel all resulted in physiological apical shapes after treatment. Eight teeth had divergent apical shapes before treatment. Of these, one had a physiological shape, five ended with rounded apices and two teeth had straight apices post-treatment. Apical closure was obtained in 100% of the cases studied, of these 88.4% needed three to four sessions of calcium hydroxide treatment (an average of 3.23 sessions) in order to obtain apical closure, the average time employed was 12.19 months. Clinical symptoms resolved in all teeth that presented with symptoms. Preoperative symptoms did not affect outcome. Pathology of the tooth before treatment does not influence the time needed to obtain apical closure. [ABSTRACT FROM AUTHOR]

Summary A study was undertaken in order to evaluate and compare ivermectin's (IVM) plasma disposition kinetic parameters after oral or intramuscular (IM) administration in horses. Ten clinically healthy adult horses, weighing 380–496 kg body weight (BW), were allocated to two experimental groups of five horses. Group I, was treated with an oral paste formulation of IVM at the manufacturer's recommended dose of 0.2 mg/kg BW. Group II, was treated IM with an injectable 1% formulation of IVM at a dose of 0.2 mg/kg BW. Blood samples were collected by jugular puncture at different times between 0.5 h and 75 days post-treatment. After plasma extraction and derivatization, samples were analysed by high-performance liquid chromatography with fluorescence detection. A computerized kinetic analysis was performed, and data were compared using the Wilcoxon signed rank test. The parent molecule was detected in plasma between 30 min and either 20 (oral) or 40 (IM) days post-treatment. Significant differences were found for the time corresponding to peak plasma concentrations (t max ) and for absorption half-life. Peak plasma concentrations (C max ) of 51.3 ± 16.1 ng/ml (mean ± SD) were obtained after oral administration and of 31.4 ± 6.0 ng/ml for the IM route. The values for area under concentration–time curve were 137.1 ± 35.9 ng day/ml for the group treated orally, and 303.2 ± 4.3 ng day/ml for the IM treated group. The mean plasma residence times were 4.2 ± 0.4 and 8.9 ± 0.7 days for oral and IM-treated groups, respectively. The results of this study show that the route of administration considerably affects the disposition of IVM. A significant difference in bioavailabilty and half-life of elimination of IVM was observed after IM administration compared with oral administration. A close relationship between pharmacokinetic profiles and the clinical efficacy of IVM was established. [ABSTRACT FROM AUTHOR]

ABSTRACT Background. ABSTExperimental evidences have suggested that a Th1 response is unable to eliminate H. pylori colonization; whereas a Th2 response, like the one induced by vaccination, reduces H. pylori infection in animal models. Some parasitic infections induce a polarized Th2 response, which theoretically would favor a reduced H. pylori prevalence. The aim of this work was to study the possible association between parasitic infections and H. pylori prevalence. Materials and Methods. The study population included 120 children and 188 adults from a low socioeconomic level village. H. pylori prevalence was determined in serum by ELISA; parasitic infections were identified in feces by microscopic examination; and total serum IgE levels, as an indirect indicator of some parasitic infections, were determined by ELISA. Results. In children, H. pylori prevalence was no different between those with and without intestinal parasitic infection. By contrast, adults with intestinal parasitic infection had a significantly lower H. pylori prevalence than adults without parasites (62.6% compared with 80.4%; p = 0.006, OR 2.45). Also in adults, but not in children, total IgE levels were significantly higher in those without H. pylori infection than in those with H. pylori infection (p < 0.001). Conclusions. Intestinal parasitic infections and serum IgE levels showed an age-dependent association with H. pylori prevalence. In adults, but not in children, intestinal parasitic infections and increased IgE levels where associated with a reduced H. pylori prevalence. [ABSTRACT FROM AUTHOR]

Examines the effectiveness of flow cytometry using monoclonal antibody CD10-Pe/Cy5 in identifying follicular lymphoma cells (FL). Types of phenotypic signs typically expressed in FL; Immunophenotypes found in neoplastic cells; Molecular deregulation of bcl-2 protein.

A letter to the editor on Riga-Fede disease an ulcerative lesion in oral mucosa of children is presented.

Wireless links using carrier waves in the millimetre-wave spectrum above 70 GHz provide a cost-effective solution to increase the data rate. Reported is the development of a photonically enabled link, based on two compact modules, both operated uncooled, transmitting a 1 Gbit/s data signal over several metres. The first module includes an optimised high-speed photodiode, delivering an output RF power exceeding 0 dBm (1 mW). Also reported is the development of a direct envelope receiver based on a quasi-optical Schottky barrier diode (SBD) module. Over the carrier frequency range, the broadband log-periodic antenna impedance has been optimised to match the SBD, while at the baseband frequency, the receiver was optimised to a 50 Ω output through an impedance transition. These have been key issues for the excellent performance of the compact receiver module over the entire E-band. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Tryptase and histamine metabolites as diagnostic indicators of indolent systemic mastocytosis without skin lesions" by J. J. Van Doormaal and colleagues in the 2012 issue and their reply to the editor is also presented.

A letter to the editor is presented regarding the case of a 27-year-old man who was diagnosed with Peutz-Jeghers syndrome (PJS) through dermoscopy.

The article describes a study to assert and compare the accuracy of the Crevat formula with other methods and to develop the best possible formula for body weigh estimation of thoroughbred foals aged 2 to 180 days old. The study used two power formulas and found that the power 1 formula gave the most accurate results while the simplified power 2 formula had a slightly lower precision. However, the authors recommend the power 2 formula because it uses easily measurable variables.

Presents a case study of an aged man who developed hypersensitivity to piperacillin. Medical history of the patient; Clinical manifestations of the condition; Findings of the laboratory exams administered to the patient.

A letter to the editor is presented in response to the article "Comparative evaluation of ultrasound-guided continuous infraclavicular brachial plexus block with stimulating catheter and traditional technique: a prospective randomized trial," by S. Dhir and S. Ganapathy.

Background: Systemic mastocytosis (SM) is a heterogeneous disease characterized by an expansion of KIT-mutated mast cells (MC). KIT-mutated MC display activated features and release MC mediators that might act on the tumour microenvironment and other immune cells. Here, we investigated the distribution of lymphocyte subsets in blood of patients with distinct subtypes of SM and determined its association with other disease features., Methods: We studied the distribution of TCD4 + and TCD4 - cytotoxic cells and their subsets, as well as total NK- and B cells, in blood of 115 SM patients-38 bone marrow mastocytosis (BMM), 67 indolent SM (ISM), 10 aggressive SM (ASM)- and 83 age-matched healthy donors (HD), using spectral flow cytometry and the EuroFlow Immunomonitoring panel, and correlated it with multilineage KIT D816V , the alpha-tryptasemia genotype (HαT) and the clinical manifestations of the disease., Results: SM patients showed decreased counts (vs. HD) of TCD4 - cytotoxic cells, NK cells and several functional subsets of TCD4 + cells (total Th1, Th2-effector memory, Th22-terminal effector and Th1-like Tregs), together with increased T-follicular-helper and Th1/Th17-like Treg counts, associated with different immune profiles per diagnostic subtype of SM, in multilineal versus MC-restricted KIT D816V and in cases with a HαT + versus HαT - genotype. Unique immune profiles were found among BMM and ISM patients with MC-restricted KIT D816V who displayed HαT, anaphylaxis, hymenoptera venom allergy, bone disease, pruritus, flushing and GI symptoms., Conclusion: Our results reveal altered T- and NK-cell immune profiles in blood of SM, which vary per disease subtype, the pattern of involvement of haematopoiesis by KIT D816V , the HαT genotype and specific clinical manifestations of the disease., (© 2024 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Aims: Shiga toxin-producing Escherichia coli-haemolytic uraemic syndrome (STEC-HUS) is considered a toxaemic disorder in which early intervention with neutralizing antibodies may have therapeutic benefits. INM004, composed of F (ab') 2 fragments from equine immunoglobulins, neutralizes Stx1/Stx2, potentially preventing the onset of HUS., Methods: A single-centre, randomized, phase 1, single-blind, placebo-controlled clinical trial to evaluate INM004 safety, tolerance and pharmacokinetics (PK) in healthy adult volunteers, was conducted; in stage I, eight subjects were divided in two cohorts (n = 4) to receive a single INM004 dose of 2 or 4 mg kg -1 , or placebo (INM004:placebo ratio of 3:1). In stage II, six subjects received three INM004 doses of 4 mg kg -1 repeated every 24 h, or placebo (INM004:placebo ratio of 5:1)., Results: Eight subjects (57.1%) experienced mild treatment-emergent adverse events (TEAEs); most frequent were rhinitis, headache and flushing, resolved within 24 h without changes in treatment or additional intervention. No serious AEs were reported. Peak concentrations of INM004 occurred within 2 h after infusion, with median C max values of 45.1 and 77.7 μg mL -1 for 2 and 4 mg kg -1 , respectively. The serum concentration of INM004 declined in a biphasic manner (t 1/2 range 30.7-52.9 h). Systemic exposures increased with each subsequent dose in a dose-proportional manner, exhibiting accumulation. Geometric median C max and AUC values were 149 and 10 300 μg h mL -1 , respectively, in the repeated dose regimen. Additionally, samples from subjects that received INM004 at 2 mg kg -1 showed neutralizing capacity against Stx1 and Stx2 in in vitro assays., Conclusions: The results obtained in this first-in-human study support progression into the phase 2 trial in children with HUS., (© 2024 British Pharmacological Society.)

Background: A close association between hereditary alpha-tryptasemia (HAT) and mast cell (MC) disorders has been previously reported. However, the relationship between HAT and the diagnostic subtypes and clinical features of MC disorders still remains to be established., Objective: To determine the prevalence of HAT in healthy donors (HD) vs patients with different diagnostic subtypes of MC activation syndromes (MCAS) and mastocytosis, and its relationship with the clinical behavior of the disease., Methods: A total of 959 subjects were studied including 346 healthy donors (HD), 464 mastocytosis, and 149 non-clonal MCAS patients. Molecular studies to assess the TPSAB1 genotype were performed, and data on serum baseline tryptase (sBT) and basal MC-mediator release episodes and triggers of anaphylaxis were collected., Results: HAT was detected in 15/346 (4%) HD versus 43/149 (29%) non-clonal MCAS and 84/464 (18%) mastocytosis cases. Among mastocytosis, HAT was more frequently found in patients with MC-restricted KIT D816V (21% vs. 10% among multilineage KIT D816V patients; p = .008). Overall, median sBT was higher in cases presenting with HAT (28.9 vs. 24.5 ng/mL; p = .008), while no significant differences in sBT were observed among HAT + mastocytosis patients depending on the presence of 1 vs. ≥2 extra copies of the α-tryptase gene (44.1 vs. 35.2 ng/mL, p > .05). In turn, anaphylaxis was more frequently observed in HAT + versus HAT - mastocytosis patients (76% vs. 65%; p = .018), while HAT + and HAT - patients who did not refer anaphylaxis as the presenting symptom (n = 308) showed a similar prevalence of subsequent anaphylaxis (35% vs. 36%, respectively)., Conclusion: The frequency of HAT in MC disorders varies according to the diagnostic subtype of the disease. HAT does not imply a higher risk (and severity) of anaphylaxis in mastocytosis patients in whom anaphylaxis is not part of the presenting symptoms of the disease., (© 2023 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background: Current diagnostic algorithms for systemic mastocytosis (SM) rely on the detection of KITD816V in blood to trigger subsequent bone marrow (BM) investigations., Methods: Here, we correlated the KITD816V mutational status of paired blood and BM samples from 368 adults diagnosed with mast cell activation syndrome (MCAS) and mastocytosis and determined the potential utility of investigating KITD816V in genomic DNA from blood-purified myeloid cell populations to increase diagnostic sensitivity. In a subset of 69 patients, we further evaluated the kinetics of the KITD816V cell burden during follow-up and its association with disease outcome., Results: Our results showed a high correlation (P < .0001) between the KITD816V mutation burden in blood and BM (74% concordant samples), but with a lower mean of KITD816V-mutated cells in blood (P = .0004) and a high rate of discordant BM + /blood - samples particularly among clonal MCAS (73%) and BM mastocytosis (51%), but also in cutaneous mastocytosis (9%), indolent SM (15%), and well-differentiated variants of indolent SM (7%). Purification of different compartments of blood-derived myeloid cells was done in 28 patients who were BM mast cell (MC) + /blood - for KITD816V, revealing KITD816V-mutated eosinophils (56%), basophils (25%), neutrophils (29%), and/or monocytes (31%) in most (61%) patients. Prognostically, the presence of ≥3.5% KITD816V-mutated cells (P < .0001) and an unstable KITD816V mutation cell burden (P < .0001) in blood and/or BM were both associated with a significantly shortened progression-free survival (PFS)., Conclusions: These results confirm the high specificity but limited sensitivity of KITD816V analysis in whole blood for the diagnostic screening of SM and other primary MCAS, which might be overcome by assessing the mutation in blood-purified myeloid cell populations., (© 2022 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background & Aim: Liver transplantation (LT) selection models for hepatocellular carcinoma (HCC) have not been proposed to predict waitlist dropout because of tumour progression. The aim of this study was to compare the alpha-foetoprotein (AFP) model and other pre-LT models in their prediction of HCC dropout., Methods: A multicentre cohort study was conducted in 20 Latin American transplant centres, including 994 listed patients for LT with HCC from 2012 to 2018. Longitudinal tumour characteristics, and patterns of progression were recorded at time of listing, after treatments and at last follow-up over the waitlist period. Competing risk regression models were performed, and model's discrimination was compared estimating Harrell's adapted c-statistics., Results: HCC dropout rate was significantly higher in patients beyond (24% [95% CI 16-28]) compared to those within Milan criteria (8% [95% IC 5%-12%]; p < .0001), with a SHR of 3.01 [95% CI 2.03-4.47]), adjusted for waiting list time and bridging therapies (c-index 0.63 [95% CI 0.57; 0.69). HCC dropout rates were higher in patients with AFP scores >2 (adjusted SHR of 3.17 [CI 2.13-4.71]), c-index of 0.71 (95% CI 0.65-0.77; p = .09 vs Milan). Similar discrimination power for HCC dropout was observed between the AFP score and the Metroticket 2.0 model. In patients within Milan, an AFP score >2 points discriminated two populations with a higher risk of HCC dropout (SHR 1.68 [95% CI 1.08-2.61])., Conclusions: Pre-transplant selection models similarly predicted HCC dropout. However, the AFP model can discriminate a higher risk of dropout among patients within Milan criteria., (© 2022 John Wiley & Sons A/S . Published by John Wiley & Sons Ltd.)

Background and Aims: PTTG1 is almost undetectable in adult livers but is highly expressed in hepatocarcinoma. While little is known about its involvement in liver fibrosis, PTTG1 expression is associated with DLK1. We assessed the role of the PTTG1/DLK1 pathway in fibrosis progression and the potential therapeutic effect of PTTG1 silencing in fibrosis., Methods: Pttg1 and Dlk1 were studied in liver and isolated cell populations of control and fibrotic rats and in human liver biopsies. The fibrotic molecular signature was analysed in Pttg1 -/- and Pttg1 +/+ fibrotic mice. Finally, Pttg1 silencing was evaluated in rats as a novel antifibrotic therapy., Results: Pttg1 and Dlk1 mRNA selectively increased in fibrotic rats paralleling fibrosis progression. Serum DLK1 concentrations correlated with hepatic collagen content and systemic and portal haemodynamics. Human cirrhotic livers showed greater PTTG1 and DLK1 transcript abundance than non-cirrhotic, and reduced collagen was observed in Pttg1 Pttg1 -/- mice. The liver fibrotic molecular signature revealed lower expression of genes related to extracellular matrix remodelling including Mmp8 and 9 and Timp4 and greater eotaxin and Mmp13 than fibrotic Pttg1 +/+ mice. Finally, interfering Pttg1 resulted in reduced liver fibrotic area, lower α-Sma and decreased portal pressure than fibrotic animals. Furthermore, Pttg1 silencing decreased the transcription of Dlk1, collagens I and III, Pdgfrβ, Tgfrβ, Timp1, Timp2 and Mmp2., Conclusions: Pttg1/Dlk1 are selectively overexpressed in the cirrhotic liver and participate in ECM turnover regulation. Pttg1 disruption decreases Dlk1 transcription and attenuates collagen deposition. PTTG1/DLK1 signalling is a novel pathway for targeting the progression of liver fibrosis., (© 2022 The Authors. Liver International published by John Wiley & Sons Ltd.)

Objective: To compare the effect of inhaled nitrous oxide (INO) on pain control during in-office hysteroscopy with 1% lidocaine paracervical infiltration and no analgesic., Design: Single-blind stratified randomised clinical trial with masked assessment by a third party., Setting: Department of Obstetrics and Gynaecology in a Spanish hospital., Population: Women who underwent hysteroscopy., Methods: Patients were stratified into three groups according to the purpose of the hysteroscopy (biopsy, polypectomy or tubal sterilisation) and then assigned to different treatment groups through a permuted-blocks randomisation within strata. Pain scale was provided by a gynaecologist totally blinded to procedures and treatments. Effects were assessed using a one-way analysis of variance following an intention-to-treat approach., Main Outcome Measures: Visual analogue scale (VAS) from 0 to 100 mm., Results: A total of 314 women were included: 105 to INO, 104 to 1% lidocaine and 105 to no analgesic. Baseline characteristics were comparable. Mean VAS score after the procedure was 34.7 ± 25.8 mm, 36.1 ± 22.9 mm (P = 1.0) and 47.3 ± 28.2 mm (P = 0.001) for INO, 1% lidocaine and no analgesic, respectively. No adverse events were reported in 91 (86.7%) patients in the INO group compared with 79 (76%) in the 1%-lidocaine group (P = 0.04) and 85 (81%) in the no-analgesic group (P = 0.26)., Conclusion: INO was as effective as 1% lidocaine in pain control for in-office hysteroscopy and was better tolerated. The no-analgesic group presented the poorer results, so was the least recommended clinical option., (© 2021 John Wiley & Sons Ltd.)

Background & Aim: Recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) has a poor prognosis, and the adjusted effect of different treatments on post-recurrence survival (PRS) has not been well defined. This study aims to evaluate prognostic and predictive variables associated with PRS., Methods: This Latin American multicenter retrospective cohort study included HCC patients who underwent LT between the years 2005-2018. We evaluated the effect of baseline characteristics at time of HCC recurrence diagnosis and PRS (Cox regression analysis). Early recurrences were those occurring within 12 months of LT. To evaluate the adjusted treatment effect for HCC recurrence, a propensity score matching analysis was performed to assess the probability of having received any specific treatment for recurrence., Results: From a total of 1085 transplanted HCC patients, the cumulative incidence of recurrence was 16.6% (CI 13.5-20.3), with median time to recurrence of 13.0 months (IQR 6.0-26.0). Factors independently associated with PRS were early recurrence (47.6%), treatment with sorafenib and surgery/trans-arterial chemoembolization (TACE). Patients who underwent any treatment presented "early recurrences" less frequently, and more extrahepatic metastasis. This unbalanced distribution was included in the propensity score matching, with correct calibration and discrimination (receiving operator curve of 0.81 [CI 0.72;0.88]). After matching, the adjusted effect on PRS for any treatment was HR of 0.2 (0.10;0.33); P < .0001, for sorafenib therapy HR of 0.4 (0.27;0.77); P = .003, and for surgery/TACE HR of 0.4 (0.18;0.78); P = .009., Conclusion: Although early recurrence was associated with worse outcome, even in this population, systemic or locoregional treatments were associated with better PRS., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The aim of the study is to determine the prevalence, outcomes, and survival (among live births [LB]), in pregnancies diagnosed with trisomy 13 (T13) and 18 (T18), by congenital anomaly register and region. Twenty-four population- and hospital-based birth defects surveillance registers from 18 countries, contributed data on T13 and T18 between 1974 and 2014 using a common data-reporting protocol. The mean total birth prevalence (i.e., LB, stillbirths, and elective termination of pregnancy for fetal anomalies [ETOPFA]) in the registers with ETOPFA (n = 15) for T13 was 1.68 (95% CI 1.3-2.06), and for T18 was 4.08 (95% CI 3.01-5.15), per 10,000 births. The prevalence varied among the various registers. The mean prevalence among LB in all registers for T13 was 0.55 (95%CI 0.38-0.72), and for T18 was 1.07 (95% CI 0.77-1.38), per 10,000 births. The median mortality in the first week of life was 48% for T13 and 42% for T18, across all registers, half of which occurred on the first day of life. Across 16 registers with complete 1-year follow-up, mortality in first year of life was 87% for T13 and 88% for T18. This study provides an international perspective on prevalence and mortality of T13 and T18. Overall outcomes and survival among LB were poor with about half of live born infants not surviving first week of life; nevertheless about 10% survived the first year of life. Prevalence and outcomes varied by country and termination policies. The study highlights the variation in screening, data collection, and reporting practices for these conditions., (© 2019 Wiley Periodicals, Inc.)

Isolated postaxial polydactyly (I-PAP), as a single defect, is a frequent malformation, characterized by an extra digit placed on the ulnar or fibular side of the limbs. Worldwide prevalence varies from as high as 225/10,000 in Nigerians to so low as 6.08/10,000 in Argentinians. Genetic-ethnic background significantly affects worldwide prevalence and type of I-PAP. Herein we describe the epidemiological characteristics of I-PAP in 697 newborns, 383 males and 314 females identified in 1,178,993 examined live births from a multicenter case-control hospital-based population study, the Mexican program of Registry and Epidemiological Surveillance of Congenital Malformations (RYVEMCE). The main characteristics analyzed included total I-PAP, stratified in Types A and B, defined as complete or incomplete extra-digit formation, respectively, sex prevalence, affected limb, laterality, parity, prematurity, delivery-type, twinning, consanguinity, and parental age. Males (6.35/10,000) are significantly more frequently affected than females (5.45/10,000), hands more than feet, left more than right limbs, and Type B (74.50%) more than A (25.50%). Prematurity and forceps use were significantly more frequent in cases than controls. An evident decreasing time-trend prevalence was present. Similar findings with other studies were males, upper and left limbs more frequently affected. Findings that were not previously reported include prematurity, forceps use, a significant decreasing time trend and an inverse ethnic prevalence for Types A (75%) and B (25%) in the Mayan population in contrast to other worldwide ethnic groups., (© 2019 Wiley Periodicals, Inc.)

The socioeconomic and medical improvements of the last decades have led to a relevant increase in the median age of worldwide population. Although numerous studies described the impact of aging in different organs and the systemic vasculature, relatively little is known about liver function and hepatic microcirculatory status in the elderly. In this study, we aimed at characterizing the phenotype of the aged liver in a rat model of healthy aging, particularly focusing on the microcirculatory function and the molecular status of each hepatic cell type in the sinusoid. Moreover, major findings of the study were validated in young and aged human livers. Our results demonstrate that healthy aging is associated with hepatic and sinusoidal dysfunction, with elevated hepatic vascular resistance and increased portal pressure. Underlying mechanisms of such hemodynamic disturbances included typical molecular changes in the cells of the hepatic sinusoid and deterioration in hepatocyte function. In a specific manner, liver sinusoidal endothelial cells presented a dysfunctional phenotype with diminished vasodilators synthesis, hepatic macrophages exhibited a proinflammatory state, while hepatic stellate cells spontaneously displayed an activated profile. In an important way, major changes in sinusoidal markers were confirmed in livers from aged humans. In conclusion, our study demonstrates for the first time that aging is accompanied by significant liver sinusoidal deregulation suggesting enhanced sinusoidal vulnerability to chronic or acute injuries., (© 2018 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.)

Background: Recent studies show that most systemic mastocytosis (SM) patients, including indolent SM (ISM) with (ISMs+) and without skin lesions (ISMs-), carry the KIT D816V mutation in PB leukocytes. We investigated the potential association between the degree of involvement of BM hematopoiesis by the KIT D816V mutation and the distribution of different maturation-associated compartments of bone marrow (BM) and peripheral blood (PB) CD34 + hematopoietic precursors (HPC) in ISM and identified the specific PB cell compartments that carry this mutation., Methods: The distribution of different maturation-associated subsets of BM and PB CD34 + HPC from 64 newly diagnosed (KIT-mutated) ISM patients and 14 healthy controls was analyzed by flow cytometry. In 18 patients, distinct FACS-purified PB cell compartments were also investigated for the KIT mutation., Results: ISM patients showed higher percentages of both BM and PB MC-committed CD34 + HPC vs controls, particularly among ISM cases with MC-restricted KIT mutation (ISM MC ); this was associated with progressive blockade of maturation of CD34 + HPC to the neutrophil lineage from ISM MC to multilineage KIT-mutated cases (ISM ML ). Regarding the frequency of KIT-mutated cases and cell populations in PB, variable patterns were observed, the percentage of KIT-mutated PB CD34 + HPC, eosinophils, neutrophils, monocytes and T cells increasing from ISMs- MC and ISMs+ MC to ISM ML patients., Conclusion: The presence of the KIT D816V mutation in PB of ISM patients is associated with (early) involvement of circulating CD34 + HPC and multiple myeloid cell subpopulations, KIT-mutated PB CD34 + HPC potentially contributing to early dissemination of the disease., (© 2018 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

We report the case of a 6-month-old Hispanic boy with a 4-month history of widespread pruritic hypopigmented papules mimicking lichen nitidus. The final diagnosis was multisystem non-risk-organ Langerhans cell histiocytosis (LCH), with cutaneous and multiple bone involvement. With this patient and others previously reported in the literature, we suggest an early biopsy of the hypopigmented rash in children., (© 2016 The Australasian College of Dermatologists.)

Problem: Trypanosoma cruzi and Toxoplasma gondii present, respectively, low and high congenital transmission rates. The placenta as an immune regulatory organ expresses TLRs, leading to the secretion of cytokines. Both parasites are recognized by TLR-2, TLR-4, and TLR-9. Here, we studied if the parasites induce differences in TLR protein expression, cytokine profiles, and whether receptor inhibition is related to parasite infection., Method of Study: Placental tissue explants were infected ex vivo with each parasite, TLRs protein expression, cytokine profile and parasite infection were determined by Western blotting, ELISA and qPCR., Results: Trypanosoma cruzi and Toxoplasma gondii infection is related to TLR-2 and TLR-4/TLR-9, respectively. Trypanosoma cruzi elicits an increase in TNF-α, IL-1β, IL-6, IL-8 and IL-10 cytokine secretion whereas T. gondii only increases the secretion of IL-8., Conclusion: The susceptibility of the placenta to each parasite is mediated partially by the innate immune response., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background & Aims: The French alpha-fetoprotein (AFP) model has recently shown superior results compared to Milan criteria (MC) for prediction of hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT) in European populations. The aim of this study was to explore the predictive capacity of the AFP model for HCC recurrence in a Latin-American cohort., Methods: Three hundred twenty-seven patients with HCC were included from a total of 2018 patients transplanted at 15 centres. Serum AFP and imaging data were both recorded at listing. Predictability was assessed by the Net Reclassification Improvement (NRI) method., Results: Overall, 82 and 79% of the patients were within MC and the AFP model respectively. NRI showed a superior predictability of the AFP model against MC. Patients with an AFP score >2 points had higher risk of recurrence at 5 years Hazard Ratio (HR) of 3.15 (P = 0.0001) and lower patient survival (HR = 1.51; P = 0.03). Among patients exceeding MC, a score ≤2 points identified a subgroup of patients with lower recurrence (5% vs 42%; P = 0.013) and higher survival rates (84% vs 45%; P = 0.038). In cases treated with bridging procedures, following restaging, a score >2 points identified a higher recurrence (HR 2.2, P = 0.12) and lower survival rate (HR 2.25, P = 0.03). A comparative analysis between HBV and non-HBV patients showed that the AFP model performed better in non-HBV patients., Conclusions: The AFP model could be useful in Latin-American countries to better select patients for LT in subgroups presenting with extended criteria. However, particular attention should be focused on patients with HBV., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The diagnosis of 'rare diseases', such as mastocytosis, remains a challenge. Despite this, the precise benefits of referral of mastocytosis patients to highly specialized reference centres are poorly defined and whether patients should be managed at non-specialized versus reference centres remains a matter of debate. To evaluate the quality and efficiency of diagnostic procedures performed at the reference centres for mastocytosis in Spain (REMA) versus other non-reference centres, we retrospectively analysed a series of 122 patients, for the overall degree of agreement obtained for the World Health Organization (WHO) diagnostic and classification criteria betwen the referring and REMA centres. Our results showed that not all WHO diagnostic criteria were frequently investigated at the referring centres. Among the five WHO diagnostic criteria, the highest degree of agreement was obtained for serum tryptase levels [median 90% (95% confidence interval 84-96%)]; in turn, the overall agreement was significantly lower for the major histopathological criterion [80% (72-89%)], and the other three minor criteria: cytomorphology [68% (56-80%)] immunophenotyping of BM mast cells [75% (62-87%)] and detection of the KIT mutation [34% (8-60%)]. Referral of patients with diagnostic suspicion of mastocytosis to a multidisciplinary reference centre improves diagnostic efficiency and quality., (© 2015 John Wiley & Sons Ltd.)

Conjoined twins (CT) are a very rare developmental accident of uncertain etiology. Prevalence has been previously estimated to be 1 in 50,000 to 1 in 100,000 births. The process by which monozygotic twins do not fully separate but form CT is not well understood. The purpose of the present study was to analyze diverse epidemiological aspects of CT, including the different variables listed in the Introduction Section of this issue of the Journal. The study was made possible using the International Clearinghouse for Birth Defects Surveillance and Research (ICBDSR) structure. This multicenter worldwide research includes the largest sample of CT ever studied. A total of 383 carefully reviewed sets of CT obtained from 26,138,837 births reported by 21 Clearinghouse Surveillance Programs (SP) were included in the analysis. Total prevalence was 1.47 per 100,000 births (95% CI: 1.32-1.62). Salient findings including an evident variation in prevalence among SPs: a marked variation in the type of pregnancy outcome, a similarity in the proportion of CT types among programs: a significant female predominance in CT: particularly of the thoracopagus type and a significant male predominance in parapagus and parasitic types: significant differences in prevalence by ethnicity and an apparent increasing prevalence trend in South American countries. No genetic, environmental or demographic significant associated factors were identified. Further work in epidemiology and molecular research is necessary to understand the etiology and pathogenesis involved in the development of this fascinating phenomenon of nature., (Copyright © 2011 Wiley Periodicals, Inc.)