Big data-based parathyroid hormone (PTH) values emphasize need for age correction.

PURPOSE: We aimed to study the relationship between aging and increased parathyroid hormone (PTH) values. METHODS: We performed a retrospective cross-sectional study with data from patients who underwent outpatient PTH measurements performed by a second-generation electrochemiluminescence immunoassay. We included patients over 18 years of age with simultaneous PTH, calcium, and creatinine measurements and 25-OHD measured within 30 days. Patients with glomerular filtration rate < 60 mL/min/1.73 m2, altered calcemia, 25-OHD level < 20 ng/mL, PTH values > 100 pg/mL or using lithium, furosemide or antiresorptive therapy were excluded. Statistical analyses were performed using the RefineR method. RESULTS: Our sample comprised 263,242 patients for the group with 25-OHD ≥ 20 ng/mL, that included 160,660 with 25-OHD ≥ 30 ng/mL. The difference in PTH values among age groups divided by decades was statistically significant (p < 0.0001), regardless of 25-OHD values, ≥ 20 or ≥ 30 ng/mL. In the group with 25-OHD ≥ 20 ng/mL and more than 60 years, the PTH values were 22.1-84.0 pg/mL, a different upper reference limit from the reference value recommended by the kit manufacturer. CONCLUSION: We observed a correlation between aging and PTH increase, when measured by a second-generation immunoassay, regardless of vitamin D levels, if greater than 20 ng/mL, in normocalcemic individuals without renal dysfunction.

Meta-analysis and systematic literature review of climate change effects on livestock welfare.

Climate change is a phenomenon that includes different dramatic events that deeply affect the physiology of animal species both directly and indirectly with qualitative-quantitative impacts on livestock performances and health. The implications of climate change on animal welfare and on production demand are complex and call for a multidisciplinary approach which involved both animal science and economic sciences. The current technical report will describe the activities performed by the fellow while placed at the University of Foggia, Department of Agriculture, Natural Resources and Engineering, in Italy. Furthermore, the work programme offered by the hosting site consisted in performing a systematic literature review, following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) Statement, and a quantitative synthesis of the literature on the impact of climate change events (e.g. heat stress) on livestock welfare and productivity and the effect of heat relieving strategies on the animals' performance.

Sparse-coding denoising applied to reversible conformational switching of a porphyrin self-assembled monolayer induced by scanning tunnelling microscopy.

Scanning tunnelling microscopy (STM) was used to induce conformational molecular switching on a self-assembled monolayer of zinc-octaethylporphyrin on a graphite/tetradecane interface at room temperature. A reversible conformational change controlled by applying a tip voltage was observed. Consecutive STM images acquired at alternating tip voltages showed that at 0.4 V the porphyrin monolayer presents a molecular arrangement formed by alternate rows with two different types of structural conformations and when the potential is increased to 0.7 V the monolayer presents only one type of conformation. In this paper, we characterize these porphyrin conformational dynamics by analyzing the STM images, which were improved for better quality and interpretation by means of a denoising algorithm, adapted to process STM images from state of the art image processing and analysis methods. STM remains the best technique to 'see' and to manipulate the matter at atomic scale. A very sharp tip a few angstroms of the surface can provide images of molecules and atoms with a powerful resolution. However, these images are strongly affected by noise which is necessary to correct and eliminate. This paper is about new computational tools specifically developed to denoise the images acquired with STM. The new algorithms were tested in STM images, obtained at room temperature, of porphyrin monolayer which presents reversible conformational change in function of the tip bias voltage. Images with high resolution, acquired in real time, show that the porphyrins have different molecular arrangements whether the tip voltage is 0.4 V or 0.7 V.

Plexopatía braquial bilateral como forma de presentación de la neuropatía hereditaria con parálisis sensible a la presión / Hereditary neuropathy with liability to pressure palsy presenting as a bilateral brachial plexopathy

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Urgent request on avian influenza.

Highly pathogenic avian influenza (HPAI) H5N8 is currently causing an epizootic in Europe, infecting many poultry holdings as well as captive and wild bird species in more than 10 countries. Given the clear clinical manifestation, passive surveillance is considered the most effective means of detecting infected wild and domestic birds. Testing samples from new species and non-previously reported areas is key to determine the geographic spread of HPAIV H5N8 2016 in wild birds. Testing limited numbers of dead wild birds in previously reported areas is useful when it is relevant to know whether the virus is still present in the area or not, e.g. before restrictive measures in poultry are to be lifted. To prevent introduction of HPAIV from wild birds into poultry, strict biosecurity implemented and maintained by the poultry farmers is the most important measure. Providing holding-specific biosecurity guidance is strongly recommended as it is expected to have a high impact on the achieved biosecurity level of the holding. This is preferably done during peace time to increase preparedness for future outbreaks. The location and size of control and in particular monitoring areas for poultry associated with positive wild bird findings are best based on knowledge of the wider habitat and flight distance of the affected wild bird species. It is recommended to increase awareness among poultry farmers in these established areas in order to enhance passive surveillance and to implement enhanced biosecurity measures including poultry confinement. There is no scientific evidence suggesting a different effectiveness of the protection measures on the introduction into poultry holdings and subsequent spread of HPAIV when applied to H5N8, H5N1 or other notifiable HPAI viruses.

Language improvement one week after thrombolysis in acute stroke.

OBJECTIVES: Language recovery following acute stroke is difficult to predict due to several evaluation factors and time constraints. We aimed to investigate the predictors of aphasia recovery and to identify the National Institute of Health and Stroke Scale (NIHSS) items that best reflect linguistic performance, 1 week after thrombolysis. MATERIALS AND METHODS: We retrieved data from a prospective registry of patients with aphasia secondary to left middle cerebral artery (MCA) stroke treated with intravenous thrombolysis. Complete recovery at day 7 (D7) was measured in a composite verbal score (CVS) (Σ Language+Questions+Commands NIHSS scores). Lesion size was categorized by the Alberta Stroke Program Early CT score (ASPECTS) and vascular patency by ultrasound. CVS was correlated with standardized aphasia testing if both were performed within a two-day interval. RESULTS: Of 228 patients included (age average 67.32 years, 131 men), 72% presented some language improvement that was complete in 31%. Total recovery was predicted by ASPECTS (OR=1.65; 95% CI, 1.295-2.108; P < 0.00) and baseline aphasia severity (OR=0.439; 95% CI, 0.242-0.796; P < 0.007). CVS correlated better with standardized aphasia measures (aphasia quotient, severity, comprehension) than NIHSS_Language item. CONCLUSIONS: Lesion size and initial aphasia severity are the main predictors of aphasia recovery one week after thrombolysis. A NIHSS composite verbal score seems to capture the global linguistic performance better than the language item alone.

Valoración de la presión pulmonar y su repercusión sobre cavidades derechas por ecocardiografía / No disponible

El presente capítulo tiene como objetivo acercar al neumólogo el conocimiento de la ecocardiografía como herramienta fundamental para la estimación de parámetros hemodinámicos de indudable importancia para el agnóstico, la estratificación del riesgo y el manejo terapéutico de la hipertensión pulmonar (HTP) y el tromboembolismo pulmonar (TEP). En general, estas mediciones ecocardiográficas muestran una excelente correlación con la hemodinámica y los métodos empleados no son excesivamente complejos, estando al alcance de cualquier profesional con un tiempo de adiestramiento muy razonable. Este texto trata de explicar, de forma gráfica y sencilla, los distintos métodos empleados en ecocardiografía para cuantificar la presión pulmonar y las resistencias vasculares pulmonares. La ecocardiografía valora, además, las repercusiones que la HTP y el TEP ejercen sobre las cavidades derechas en su intento de adaptación, permitiéndonos analizar los principales parámetros de morfología y función ventricular derecha, que han demostrado tener un valor pronóstico en estas patologías

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Increased IL6 plasma levels in indolent systemic mastocytosis patients are associated with high risk of disease progression.

Systemic mastocytosis (SM) is a heterogeneous disease with altered interleukin (IL)-6 and IL13 plasma levels. However, no study has simultaneously investigated the plasma levels of IL1ß, IL6, IL13, CCL23 and clusterin in SM at diagnosis and correlated them with disease outcome. Here we investigated IL1ß, IL6, IL13, CCL23 and clusterin plasma levels in 75 SM patients--66 indolent SM (ISM) and 9 aggressive SM--and analyzed their prognostic impact among ISM cases grouped according to the extent of hematopoietic involvement of the bone marrow cells by the KIT D816V mutation. Although increased IL1ß, IL6 and CCL23 levels were detected in SM patients versus healthy controls, only IL6 and CCL23 levels gradually increased with disease severity. Moreover, increased IL6 plasma levels were associated with ISM progression to more aggressive disease, in particular among ISM patients with multilineal KIT mutation (ISM-ML), these patients also showing a higher frequency of organomegalies, versus other ISM-ML patients. Of note, all ISM patients who progressed had increased IL6 plasma levels already at diagnosis. Our results indicate that SM patients display an altered plasma cytokine profile already at diagnosis, increased IL6 plasma levels emerging as an early marker for disease progression among ISM cases, in particular among high-risk ISM patients who carry multilineage KIT mutation.

Anaphylaxis as a clinical manifestation of clonal mast cell disorders.

Clonal mast cell disorders comprise a heterogeneous group of disorders characterized by the presence of gain of function KIT mutations and a constitutively altered activation-associated mast cell immunophenotype frequently associated with clinical manifestations related to the release of mast cells mediators. These disorders do not always fulfil the World Health Organization (WHO)-proposed criteria for mastocytosis, particularly when low-sensitive diagnostic approaches are performed. Anaphylaxis is a frequent presentation of clonal mast cell disorders, particularly in mastocytosis patients without typical skin lesions. The presence of cardiovascular symptoms, e.g., hypotension, occurring after a hymenoptera sting or spontaneously in the absence of cutaneous manifestations such as urticaria is characteristic and differs from the presentation of anaphylaxis in the general population without mastocytosis.

Current state of biology and diagnosis of clonal mast cell diseases in adults.

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.

Increased serum baseline tryptase levels and extensive skin involvement are predictors for the severity of mast cell activation episodes in children with mastocytosis.

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 (sbT) 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 sbT in association with extensive cutaneous involvement identifies patients at risk for severe MC activation events in pediatric mastocytosis.

Validation of the REMA score for predicting mast cell clonality and systemic mastocytosis in patients with systemic mast cell activation symptoms.

BACKGROUND: A variable percentage of patients with systemic mast cell (MC) activation symptoms meet criteria for systemic mastocytosis (SM). We prospectively evaluated the clinical utility of the REMA score versus serum baseline tryptase (sBt) levels for predicting MC clonality and SM in 158 patients with systemic MC activation symptoms in the absence of mastocytosis in the skin (MIS). METHODS: World Health Organization criteria for SM were applied in all cases. MC clonality was defined as the presence of KIT-mutated MC or by a clonal HUMARA test. The REMA score consisted of the assignment of positive or negative points as follows: male (+1), female (-1), sBt <15 µg/l (-1) or >25 µg/l (+2), presence (-2) or absence (+1) of pruritus, hives or angioedema and presence (+3) of presyncope or syncope. Efficiency of the REMA score for predicting MC clonality and SM was assessed by receiver operating characteristic (ROC) curve analyses and compared to those obtained by means of sBt levels alone. RESULTS: Molecular studies revealed the presence of clonal MC in 68/80 SM cases and in 11/78 patients who did not meet the criteria for SM. ROC curve analyses confirmed the greater sensitivity and a similar specificity of the REMA score versus sBt levels (84 vs. 59% and 74 vs. 70% for MC clonality and 87 vs. 62% and 73 vs. 71% for SM, respectively). CONCLUSIONS: Our results confirm the clinical utility of the REMA score to predict MC clonality and SM in patients suffering from systemic MC activation symptoms without MIS.

An immature immunophenotype of bone marrow mast cells predicts for multilineage D816V KIT mutation in systemic mastocytosis.

D816V KIT mutation of bone marrow (BM) mast cells (MC) is a common feature to systemic mastocytosis (SM) patients. Nevertheless, occurrence of the KIT mutation in BM cell compartments other than MC is associated with progression to more aggressive forms of the disease and poor outcome in indolent SM (ISM). Here, we assessed the potential association between the immunophenotype of MC and multilineage KIT mutation in the BM of SM patients through the investigation of the flow cytometric protein expression profile (PEP) of bone marrow mast cells (BMMC) from 70 control individuals and 206 SM patients, classified according to the WHO (World Health Organization), and the degree of involvement of BM hematopoiesis by the D816V KIT mutation; additionally, we developed a score-based class prediction algorithm for the detection of SM cases with multilineage mutation. Our results show that aberrant expression of CD25 with a FcɛRI(lo), FSC(lo), SSC(lo) and CD45(lo) immature phenotype of BMMC, in the absence of coexisting normal MC in the BM, was associated with multilineage involvement by the D816V KIT mutation, regardless of the diagnostic subtype of the disease (for example, indolent vs aggressive SM), which supports the utility of the immunophenotype of BMMC as a surrogate marker to screen for multilineage KIT mutation in ISM.

Spectroscopy and single-molecule emission of a fluorene-terthiophene oligomer.

We study the thiophene-based oligomer poly[2,7-(9,9-bis(2'-ethylhexyl)fluorene)-alt-2,5-terthiophene] (PF3T) in solution and when dispersed at low concentration into a polynorbornene matrix. We find that at high concentration in solution the 0-0 electronic transition observed in fluorescence is suppressed, a result indicative of the formation of weakly coupled H-aggregates. At low concentration in a polymer matrix, emission from both single molecules and molecular aggregates is observed. We find that the fluorescence spectra of most PF3T emitters are composed of a number of relatively narrow emission features, indicating that the emission usually occurs from multiple chromophores. A small number of PF3T molecules are however characterized by single chromophore emission, spectral blinking, and narrowed emission peaks.

Dermoscopic features of skin lesions in patients with mastocytosis.

OBJECTIVES: To evaluate dermoscopic features in a group of 127 patients with mastocytosis in the skin and to investigate the relationship between different dermoscopic patterns and other clinical and biological characteristics of the disease. DESIGN: Clinical and laboratory data were compared among patients with mastocytosis grouped according to the different dermoscopic patterns. SETTING: Patients were selected from the Instituto de Estudios de Mastocitosis de Castilla La Mancha and the Department of Dermatology of Hospital Universitario Ramón y Cajal from April 1 through September 30, 2009. Patients Overall, 127 consecutive patients (70 females [55.1%] and 57 males [44.9%]; median age, 17 years; range, 0-81 years) with mastocytosis in the skin were included in the study. MAIN OUTCOME MEASURES: Evaluation of dermoscopic patterns and investigation of potential predictive factors for more symptomatic forms of the disease according to the need for daily antimediator therapy. RESULTS: Four distinct dermoscopic patterns were observed: yellow-orange blot, pigment network, reticular vascular pattern, and (most frequently) light-brown blot. A reticular vascular pattern was identified in all telangiectasia macular eruptiva and some maculopapular mastocytosis. In turn, all patients with mastocytoma displayed the yellow-orange blot pattern. The reticular vascular dermoscopic pattern was associated with the need for daily antimediator therapy; this pattern, together with serum tryptase levels and plaque-type mastocytosis, represented the best combination of independent factors to predict the need for maintained antimediator therapy. CONCLUSIONS: Dermoscopy is a feasible method for the subclassification of mastocytosis. Of note, a reticular vascular pattern is more frequently associated with the need for antimediator therapy.