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Neurofibromatosis type 1 (NF1) is a progressive multisystem disorder following an autosomal dominant inheritance pattern that presents with multiple neurological manifestations.We reviewed medical histories of patients with NF1 followed up at our hospital's paediatric neurology department from May 1990 to 31 December 2018. We collected data on neurological symptoms.A total of 128 patients with NF1 were identified. Mean age (SD) at NF1 diagnosis was 4.43 (3.38) years (range, 0.5-14.5 years). There was a slight female predominance (53.1%). Macrocephaly (head circumference over 2 SDs above average for age) was present in 37.5% of cases. Attention-deficit/hyperactivity disorder was recorded in 28.9% of patients (37): combined type in 20 patients, predominantly inattentive in 15, and predominantly impulsive/hyperactive in 2. Other manifestations included headache (18.6%), cognitive impairment (7.8%), motor deficit (6.2%), and epilepsy (4.68%). Brain MRI was performed in 85 patients, revealing T2-weighted hyperintensities in the basal ganglia and/or cerebellum in 60 patients (70.5%), Chiari malformation type 1 in 4 cases, and arachnoid cysts in 3. Optic nerve gliomas were identified by MRI in 22 patients (25.8%). Other MRI findings included plexiform neurofibromas (9.3%) and central nervous system gliomas (3.1%).The neurological manifestations identified in our sample are consistent with those reported in the literature. Effective transfer strategies from paediatric neurology departments and subsequent clinical follow-up by adult neurology departments are needed to prevent loss to follow-up in adulthood.

Contains fulltext : 249977.pdf (Publisher’s version ) (Closed access) BACKGROUND: It is important to evaluate whether a new treatment for heart failure with reduced ejection fraction (HFrEF) provides additive benefit to background foundational treatments. As such, we aimed to evaluate the efficacy and safety of empagliflozin in patients with HFrEF in addition to baseline treatment with specific doses and combinations of disease-modifying therapies. METHODS: We performed a post-hoc analysis of the EMPEROR-Reduced randomised, double-blind, parallel-group trial, which took place in 520 centres (hospitals and medical clinics) in 20 countries in Asia, Australia, Europe, North America, and South America. Patients with New York Heart Association (NYHA) classification II-IV with an ejection fraction of 40% or less were randomly assigned (1:1) to receive the addition of either oral empagliflozin 10 mg per day or placebo to background therapy. The primary composite outcome was cardiovascular death and heart failure hospitalisation; the secondary outcome was total heart failure hospital admissions. An extended composite outcome consisted of inpatient and outpatient HFrEF events was also evaluated. Outcomes were analysed according to background use of angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs) or angiotensin receptor neprilysin inhibitors (ARNIs), as well as β blockers and mineralocorticoid receptor antagonists (MRAs) at less than 50% or 50% or more of target doses and in various combinations. This study is registered with ClinicalTrials.gov, NCT03057977. FINDINGS: In this post-hoc analysis of 3730 patients (mean age 66·8 years [SD 11·0], 893 [23·9%] women; 1863 [49·9%] in the empagliflozin group, 1867 [50·1%] in the placebo group) assessed between March 6, 2017, and May 28, 2020, empagliflozin reduced the risk of the primary outcome (361 in 1863 participants in the empagliflozin group and 462 of 1867 in the placebo group; HR 0·75 [95% CI 0·65-0·86]) regardless of background therapy or its target doses for ACE inhibitors or ARBs at doses of less than 50% of the target dose (HR 0·85 [0·69-1·06]) and for doses of 50% or more of the target dose (HR 0·67 [0·52-0·88]; p(interaction)=0·18). A similar result was seen for β blockers at doses of less than 50% of the target dose (HR 0·66 [0·54-0·80]) and for doses of 50% or more of the target dose (HR 0·81 [0·66-1·00]; p(interaction)=0·15). Empagliflozin also reduced the risk of the primary outcome irrespective of background use of triple therapy with an ACE inhibitor, ARB, or ARNI plus β blocker plus MRA (given combination HR 0·73 [0·61-0·88]; not given combination HR 0·76 [0·62-0·94]; p(interaction)=0·77). Similar patterns of benefit were observed for the secondary and extended composite outcomes. Empagliflozin was well tolerated and rates of hypotension, symptomatic hypotension, and hyperkalaemia were similar across all subgroups. INTERPRETATION: Empagliflozin reduced serious heart failure outcomes across doses and combinations of disease-modifying therapies for HFrEF. Clinically, these data suggest that empagliflozin might be considered as a foundational therapy in patients with HFrEF regardless of their existing background therapy. FUNDING: Boehringer Ingelheim and Eli Lilly and Company.

Since NLRP3 inflammasome plays a pivotal role in several neurodegenerative disorders, we hypothesized that levels of inflammasome components could help in diagnosis or prognosis of amyotrophic lateral sclerosis (ALS). Gene and protein expression was assayed by RT-PCR and Western blot. Spearman’s correlation coefficient was used to determine the linear correlation of transcriptional expression levels with longevity throughout disease progression in mice models. Kaplan-Meier analysis was performed to evaluate MCC950 effects (NLRP3 inhibitor) on lifespan of SOD1G93A mice. The results showed significant alterations in NLRP3 inflammasome gene and protein levels in the skeletal muscle of SOD1G93A mice. Spearman’s correlation coefficient revealed a positive association between Nlrp3 transcriptional levels in skeletal muscle and longevity of SOD1G93A mice (r = 0.506, p = 0.027). Accordingly, NLRP3 inactivation with MCC950 decreased the lifespan of mice. Furthermore, NLRP3 mRNA levels were significantly elevated in the blood of ALS patients compared to healthy controls (p = 0.03). In conclusion, NLRP3 could be involved in skeletal muscle pathogenesis of ALS, either through inflammasome or independently, and may play a dual role during disease progression. NLRP3 gene expression levels could be used as a biomarker to improve diagnosis and prognosis in skeletal muscle from animal models and also to support diagnosis in clinical practice with the blood of ALS patients.

Highlights • Children with COVID 19 disease are less symptomatic but they can be potential agents of transmission. • Most children with symptoms from COVID 19 disease (cough, fever, respiratory difficulties) show bnormalities in CXR. • Findings in CXR are non-specific and superimpose on other viral pneumonias. • Peripheral distribution of lung abnormalities is not a distinctive feature in paediatric population. • CXR have a role in the management of the disease in children., BACKGROUND The outbreak of COVID-19 has become pandemic. Pediatric population has been less studied than adult population and prompt diagnosis is challenging due to asymptomatic or mild episodes. Radiology is an important complement to clinical and epidemiological features. OBJECTIVE To establish the most common CXR patterns in children with COVID-19, evaluate interobserver correlation and to discuss the role of imaging techniques in the management of children. MATERIALS AND METHODS Forty-four patients between 0 and 16 years of age with confirmed SARS-Cov-2 infection and CXR were selected. Two paediatric radiologists independently evaluated the images and assessed the type of abnormality, distribution and evolution when available. RESULTS Median age was 79.8 months (ranging from 2 weeks to 16 years of age). Fever was the most common symptom (43.5 %). 90 % of CXR showed abnormalities. Peribronchial cuffing was the most common finding (86.3 %) followed by GGOs (50 %). In both cases central distribution was more common than peripheral. Consolidations accounted for 18.1 %. Normal CXR, pleural effusion, and altered cardiomediastinal contour were the least common. CONCLUSION The vast majority of CXR showed abnormalities in children with COVID-19. However, findings are nonspecific. Interobserver correlation was good in describing consolidations, normal x-rays and GGOs. Imaging techniques have a role in the management of children with known or suspected COVID-19, especially in those with moderate or severe symptoms or with underlying risk factors.

Neuroinflammation plays a significant role in amyotrophic lateral sclerosis (ALS) pathology, leading to the development of therapies targeting inflammation in recent years. Our group has studied the tetanus toxin C-terminal fragment (TTC) as a therapeutic molecule, showing neuroprotective properties in the SOD1G93A mouse model. However, it is unknown whether TTC could have some effect on inflammation. The objective of this study was to assess the effect of TTC on the regulation of inflammatory mediators to elucidate its potential role in modulating inflammation occurring in ALS. After TTC treatment in SOD1G93A mice, levels of eotaxin-1, interleukin (IL)-2, IL-6 and macrophage inflammatory protein (MIP)-1 alpha (α) and galectin-1 were analyzed by immunoassays in plasma samples, whilst protein expression of caspase-1, IL-1β, IL-6 and NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) was measured in the spinal cord, extensor digitorum longus (EDL) muscle and soleus (SOL) muscle. The results showed reduced levels of IL-6 in spinal cord, EDL and SOL in treated SOD1G93A mice. In addition, TTC showed a different role in the modulation of NLRP3 and caspase-1 depending on the tissue analyzed. In conclusion, our results suggest that TTC could have a potential anti-inflammatory effect by reducing IL-6 levels in tissues drastically affected by the disease. However, further research is needed to study more in depth the anti-inflammatory effect of TTC in ALS.

Background: There is growing evidence of the role of inflammation in Amyotrophic Lateral Sclerosis (ALS) during the last decade. Although the origin of ALS remains unknown, multiple potential inflammatory biomarkers have been described in ALS patients and murine models of this disease to explain the progressive motor neuron loss and muscle atrophy. However, the results remain controversial. To shed light on this issue, we aimed to identify novel biomarkers of inflammation that can influence disease progression and survival in serial blood samples from transgenic SOD1G93A mice, a model of ALS. Methods: A cytokine array assay was performed to analyze protein expression of 97 cytokines in plasma samples from wildtype controls and transgenic SOD1G93A mice at asymptomatic stage. Subsequently, serial plasma samples were obtained from SOD1G93A mice at early symptomatic, symptomatic and terminal stages to monitor cytokine levels during disease progression through immunoassays. Comparisons of means of quantifiable cytokines between short-and long-lived mice were analyzed by unrelated t-test or Mann-Whitney U-test. Relationships between cytokines levels and survival time were assessed using Pearson's correlation analysis and Kaplan-Meier analysis. Results: A total of 16 cytokines (6Ckine, ALK-1, CD30 L, eotaxin-1, galectin-1, GITR, IL-2, IL-6, IL-10, IL-13, IL-17B R, MIP-1α, MIP-3β, RANKL, TROY, and VEGF-D) were found dysregulated in transgenic SOD1G93A mice at asymptomatic stage compared with age-matched controls. Immunoassays of serial samples revealed positive expression of ALK-1, GITR and IL-17B R at P60 and P90 in mice with shorter survival. In addition, eotaxin-1 and galectin-1 levels were significantly increased at terminal stage in SOD1G93A mice that showed shorter survival time. Finally, levels of eotaxin-1, galectin-1, IL-2, IL-6, MIP-1α, and TROY at P90 or endpoint negatively correlated with the longevity of transgenic mice. Conclusions: We demonstrated in the SOD1G93A model of ALS that increased levels of several cytokines were associated with a shorter lifespan. However, their role as prognostic biomarkers is unclear as their expression was very variable depending on both the disease stage and the subject. Nevertheless, cytokines may be potential therapeutic targets.

The pathophysiological mechanisms of both familial and sporadic Amyotrophic Lateral Sclerosis (ALS) are unknown, although growing evidence suggests that skeletal muscle tissue is a primary target of ALS toxicity. Skeletal muscle biopsies were performed on transgenic SOD1(G93A) mice, a mouse model of ALS, to determine genetic biomarkers of disease longevity. Mice were anesthetized with isoflurane, and three biopsy samples were obtained per animal at the three main stages of the disease. Transcriptional expression levels of seventeen genes, Ankrd1, Calm1, Col19a1, Fbxo32, Gsr, Impa1, Mef2c, Mt2, Myf5, Myod1, Myog, Nnt, Nogo A, Pax7, Rrad, Sln and Snx10, were tested in each muscle biopsy sample. Total RNA was extracted using TRIzol Reagent according to the manufacturer's protocol, and variations in gene expression were assayed by real-time PCR for all of the samples. The Pearson correlation coefficient was used to determine the linear correlation between transcriptional expression levels throughout disease progression and longevity. Consistent with the results obtained from total skeletal muscle of transgenic SOD1(G93A) mice and 74-day-old denervated mice, five genes (Mef2c, Gsr, Col19a1, Calm1 and Snx10) could be considered potential genetic biomarkers of longevity in transgenic SOD1(G93A) mice. These results are important because they may lead to the exploration of previously unexamined tissues in the search for new disease biomarkers and even to the application of these findings in human studies.

Amyotrophic Lateral Sclerosis (ALS) has lately become a suitable scenario to study the interplay between the hematopoietic system and disease progression. Recent studies in C9orf72 null mice have demonstrated that C9orf72 is necessary for the normal function of myeloid cells. In this study, we aimed to analyze in depth the connection between the hematopoietic system and secondary lymphoid (spleen) and non-lymphoid (liver and skeletal muscle) organs and tissues along the disease progression in the transgenic SOD1G93A mice. Our findings suggested that the inflammatory response due to the neurodegeneration in this animal model affected all three organs and tissues, especially the liver and the skeletal muscle. However, the liver was able to compensate this inflammatory response by means of the action of non-inflammatory monocytes, while in the skeletal muscle inflammatory monocytes prompted a further inflammation process until the terminal state of the animals. Interestingly, in blood, a positive correlation was found between non-inflammatory monocytes and survival of the transgenic SOD1G93A mice, while the contrary (a negative correlation) was found in the case of inflammatory monocytes, supporting their potential role as biomarkers of disease progression and survival in this animal model. These findings could prompt future translational studies in ALS patients, promoting the identification of new reliable biomarkers of disease progression.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease of unknown origin and characterized by a relentless loss of motor neurons that causes a progressive muscle weakness until death. Among the several pathogenic mechanisms that have been related to ALS, a dysregulation of calcium-buffering proteins in motor neurons of the brain and spinal cord can make these neurons more vulnerable to disease progression. Downstream regulatory element antagonist modulator (DREAM) is a neuronal calcium-binding protein that plays multiple roles in the nucleus and cytosol. The main aim of this study was focused on the characterization of DREAM and glial fibrillary acid protein (GFAP) in the brain and spinal cord tissues from transgenic SOD1G93A mice and ALS patients to unravel its potential role under neurodegenerative conditions. The DREAM and GFAP levels in the spinal cord and different brain areas from transgenic SOD1G93A mice and ALS patients were analyzed by Western blot and immunohistochemistry. Our findings suggest that the calcium-dependent excitotoxicity progressively enhanced in the CNS in ALS could modulate the multifunctional nature of DREAM, strengthening its apoptotic way of action in both motor neurons and astrocytes, which could act as an additional factor to increase neuronal damage. The direct crosstalk between astrocytes and motor neurons can become vulnerable under neurodegenerative conditions, and DREAM could act as an additional switch to enhance motor neuron loss. Together, these findings could pave the way to further study the molecular targets of DREAM to find novel therapeutic strategies to fight ALS.

Background The PCSK 9 antibody alirocumab (75 mg every 2 weeks; Q2W) as monotherapy reduced low‐density lipoprotein‐cholesterol ( LDL ‐C) levels by 47%. Because the option of a monthly dosing regimen is convenient, ODYSSEY CHOICE II evaluated alirocumab 150 mg Q4W in patients with inadequately controlled hypercholesterolemia and not on statin (majority with statin‐associated muscle symptoms), receiving treatment with fenofibrate, ezetimibe, or diet alone. Methods and Results Patients were randomly assigned to placebo, alirocumab 150 mg Q4W or 75 mg Q2W (calibrator arm), with dose adjustment to 150 mg Q2W at week (W) 12 if W8 predefined LDL ‐C target levels were not met. The primary efficacy endpoint was LDL ‐C percentage change from baseline to W24. Mean baseline LDL ‐C levels were 163.9 mg/dL (alirocumab 150 mg Q4W, n=59), 154.5 mg/dL (alirocumab 75 mg Q2W, n=116), and 158.5 mg/dL (placebo, n=58). In the alirocumab 150 mg Q4W and 75 mg Q2W groups (49.1% and 36.0% of patients received dose adjustment, respectively), least‐squares mean LDL ‐C changes from baseline to W24 were −51.7% and −53.5%, respectively (placebo [+4.7%]; both groups P LDL ‐C targets at W24. Treatment‐emergent adverse events occurred in 77.6% (alirocumab 150 mg Q4W), 73.0% (alirocumab 75 mg Q2W), and 63.8% (placebo) of patients, with injection‐site reactions among the most common treatment‐emergent adverse events. Conclusions Alirocumab 150 mg Q4W can be considered in patients not on statin with inadequately controlled hypercholesterolemia as a convenient option for lowering LDL ‐C. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 02023879.

Background: Amyotrophic lateral sclerosis (ALS) is the most common adult-onset neurodegenerative disease characterized by ascending muscle weakness, atrophy and paralysis. Early muscle abnormalities that precede motor neuron loss in ALS may destabilize neuromuscular junctions, and we have previously demonstrated alterations in myogenic regulatory factor (MRF) expression in vivo and in the activation of myofiber-associated skeletal muscle satellite cells (SMSCs) in the mouse model of ALS (SOD1-G93A). Methods: To elucidate niche dependence versus cell-autonomous mutant SOD1 (mSOD1) toxicity in this model, we measured in vitro proliferation potential and MRF and cyclin gene expression in SMSC cultures derived from fast-twitch extensor digitorum longus and slow-twitch soleus muscles of SOD1-G93A mice. Results: SMSCs from early presymptomatic (p40) to terminal, semi-paralytic (p120) SOD1-G93A mice demonstrated generally lower proliferation potential compared with age-matched controls. However, induced proliferation was observed in surgically denervated wild-type animals and SOD1-G93A animals at p90, when critical denervation arises. SMSCs from fast and slow muscles were similarly affected by mSOD1 expression. Lowered proliferation rate was generally corroborated with decreased relative MRF expression levels, although this was most prominent in early age and was modulated by muscle type origin. Cyclins controlling cell proliferation did not show modifications in their mRNA levels; however, the expression of cyclin-dependent kinase inhibitor 1A (Cdkn1a), which is known to promote myoblast differentiation, was decreased in SOD1-G93A cultures. Conclusions: Our data suggest that the function of SMSCs is impaired in SOD1-G93A satellite cells from the earliest stages of the disease when no critical motor neuron loss has been described.

Objectives Highly active antiretroviral therapy (HAART) has dramatically changed the natural history of HIV infection in children, but there are few studies in the literature about the incidence of clinical manifestations after HAART in this population, compared with adults. The aim of this study was to describe the influence of the widespread use of HAART on the development of opportunistic infections and organ-specific diseases in HIV-infected children. Methods An observational study of a cohort of 366 vertically HIV-infected children followed from 1990 to 2006 was carried out. According to the main antiretroviral protocol used, three calendar periods (CPs) were defined and compared: CP1 (1990–1996: no patients on HAART), CP2 (1997–1999: 60% on HAART). Results Children experienced a progressive increase in CD4 T cell count (P

The Erdheim-Chester disease (ECD) is an extremely rare form of non-Langerhans cell histiocytosis. The main difficulty for its diagnosis lies in the wide variety of non-specific symptoms and signs that can occur in the disease process, leading, therefore, to there being no clear-cut algorithm as a guide for an optimal biopsy to confirm the diagnosis. An 81-year-old male with history of diabetes insipidus was admitted due to non-specific respiratory signs. Imaging techniques revealed osteoblastic lesions in the lumbar spine. Whole-body bone-scintigraphy (BS) was performed, in which lesions involving the axial and appendicular skeleton, with different rates of osteoblastic activity, were observed. This highlighted a symmetrical severely intense uptake in the knees, leading to an accurate biopsy specimen that enabled making the definitive diagnosis. BS is a widely available, safe, and inexpensive technique that shows a characteristic pattern of uptake for ECD, thus its use is highly recommended for screening and guiding biopsy if clinical suspicion exists. Furthermore, when the scintigraphy pattern is incidentally observed, biopsy of increased uptake areas (tibia preferably) is mandatory in order to rule out the disease.

This article belongs to the Special Issue Gluten Related Disorders: "People Shall not Live on Bread Alone".-- This is an open access article distributed under the Creative Commons Attribution License (CC BY)., Celiac Disease (CD) is an interferon (IFN)γ-mediated duodenal hypersensitivity to wheat gluten occurring in genetically predisposed individuals. Gluten-free diet (GFD) leads to a complete remission of the disease. Vα24-restricted invariant NKT (iNKT) cells are important to maintain immune homeostasis in the gut mucosa because of their unique capacity to rapidly produce large quantities of both T-helper (Th)1 and Th2 cytokines upon stimulation. We studied the presence of these cells in the CD duodenum. Duodenal biopsies were obtained from 45 untreated-CD patients (uCD), 15 Gluten Free Diet-CD patients (GFD-CD), 44 non-inflamed non-CD controls (C-controls) and 15 inflamed non-CD controls (I-controls). Two populations from Spain and Argentina were recruited. Messenger RNA (mRNA) expression of Vα24-Jα18 (invariant TCRα chain of human iNKT cells), IFNγ and intracellular transcription factor Forkhead Box P3 (Foxp3), and flow cytometry intraepithelial lymphocyte (IEL) profile were determined. Both uCD and GFD-CD patients had higher Vα24-Jα18 mRNA levels than non-CD controls (I and C-controls). The expression of Vα24-Jα18 correlated with Marsh score for the severity of mucosal lesion and also with increased mRNA IFNγ levels. uCD and GFD-CD patients had decreased mRNA expression of FoxP3 but increased expression of Vα24-Jα18, which revealed a CD-like molecular profile. Increased numbers of iNKT cells were confirmed by flow cytometry within the intraepithelial lymphocyte compartment of uCD and GFD-CD patients and correlated with Vα24-Jα18 mRNA expression. In conclusion, we have found an increased number of iNKT cells in the duodenum from both uCD and GFD-CD patients, irrespective of the mucosal status. A CD-like molecular profile, defined by an increased mRNA expression of Vα24-Jα18 together with a decreased expression of FoxP3, may represent a pro-inflammatory signature of the CD duodenum., This work was supported by grants (to E A) from Instituto de Salud Carlos III-FEDER (PI070244, PI10/01647); (to J A G) Junta de Castilla y León (SAN673/VA22-08) and (to E M) Beca FPI-Junta de Castilla y León/Fondo Social Europeo., We acknowledge support by the CSIC Open Access Publication Initiative through its Unit of Information Resources for Research (URICI).

Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease characterized by a selective loss of motor neurons together with a progressive muscle weakness. Albeit the pathophysiological mechanisms of the disease remain unknown, growing evidence suggests that skeletal muscle can be a target of ALS toxicity. In particular, the two main intracellular degradation mechanisms, autophagy and the ubiquitin-proteasome degradative system (UPS) have been poorly studied in this tissue. In this study we investigated the activation of autophagy and the UPS as well as apoptosis in the skeletal muscle from SOD1G93A mice along disease progression. Our results showed a significant upregulation of proteasome activity at early symptomatic stage, while the autophagy activation was found at presymptomatic and terminal stages. The mRNA upregulated levels of LC3, p62, Beclin1, Atg5 and E2f1 were only observed at symptomatic and terminal stages, which reinforced the time-point activation of autophagy. Furthermore, no apoptosis activation was observed along disease progression. The combined data provided clear evidence for the first time that there is a time-point dependent activation of autophagy and UPS in the skeletal muscle from SOD1G93A mice.

[ES] Antecedentes: El rinovirus se considera un agente causal de cuadros catarrales banales, sin embargo se ha descrito como un agente inductor de exacerbaciones asmáticas en adultos y niños mayores. En nuestro medio no se ha descrito el papel del rinovirus en infecciones respiratorias de niños hospitalizados. Objetivos: Describir las infecciones confirmadas por rinovirus en niños hospitalizados por infección respiratoria en un hospital de segundo nivel. Pacientes y métodos: Estudio descriptivo prospectivo de las infecciones confirmadas por rinovirus en niños hospitalizados por fiebre o infección respiratoria en la temporada 2004-2005. Para el diagnóstico virológico se realizó inmunofluorescencia y reacción en cadena de la polimerasa (PCR) en aspirado nasofaríngeo. Se describen las características clínicas de los pacientes. Resultados: Se describen un total de 76 niños hospitalizados con infección por rinovirus, lo que supuso el 25 % de los pacientes hospitalizados por procesos respiratorios o fiebre. El rinovirus fue el segundo agente viral identificado tras el virus respiratorio sincitial (29,9% de los hospitalizados). El 71,1 % de los pacientes fueron menores de 2 años. Los diagnósticos más frecuentes fueron sibilancias recurrentes en el 60,5 %, bronquiolitis en 23,7 %, neumonía en el 7,9 % e infección respiratoria de vías altas en el 5,3%. Presentaron fiebre de más de 38 °C el 57,9 % de los niños e infiltrado radiológico el 23,7%. Presentaron hipoxia el 43,4% de los niños. En niños mayores de 2 años el diagnóstico fue crisis asmática en 21 de los 22 casos. Conclusiones: Los rinovirus se detectaron en un importante porcentaje de los niños hospitalizados a consecuencia de infección respiratoria, siendo precedidos en frecuencia sólo por el virus respiratorio sincitial. En nuestra serie es el agente viral más frecuentemente asociado con episodios de sibilancias recurrentes en niños mayores de 2 años, y el segundo en los más pequeños. [EN] Background: Rhinovirus is a recognized cause of common cold and has been shown to cause asthma exacerbations in adults and children. The burden of rhinovirus infections in hospitalized children has not been described in Spain. Objective: To describe confirmed rhinovirus infections in children hospitalized for respiratory tract infection in a secondary public hospital. Patients and methods: We performed a prospective descriptive study in children admitted to hospital with fever or respiratory tract infection and with a positive isolation of rhinovirus in nasopharyngeal washings between September 2004 and July 2005. Virological diagnosis was made with direct immunofluorescent assay and/or reverse transcription-polymerase chain reaction in specimens obtained from nasopharyngeal washings. The clinical characteristics of the patients were analyzed. Results: There were 76 children with rhinovirus infection, representing 25 % of admissions in 304 children with fever or respiratory tract infection. Rhinovirus was the second most frequent viral agent identified after respiratory syncytial virus (RSV) (29.9 % of admissions). Fifty-four children (71.1 %) were under 2 years of age. The most frequent clinical diagnoses were recurrent wheezing in 60.5 %, bronchiolitis in 23.7 %, pneumonia in 7.9 %, and upper respiratory tract infection in 5.3 %. Fever > 38 degrees C was present in 57.9 % of the patients and radiologic infiltrate was found in 23.7 %. Oxygen saturation less than 95 % was found in 43.4 % of the patients. Of 22 children aged more than 2 years, a diagnosis of asthmatic crisis was made in 21. Conclusions: Rhinoviruses were frequently identified in hospitalized children with respiratory tract disease and were the second most common viruses after RSV. In our series, it was the most frequent cause of recurrent wheezing in hospitalized children and the second most common cause in infants. Estudio parcialmente financiado por el Fondo de Investigaciones Sanitarias.FIS N.º 98/0310. Sí

To assess predictive value of the cardiovascular prognosis by comparing the two most used formulas for the estimation of glomerular filtration rate in hypertensive patients.A retrospective cohort study was designed that included 405 patients diagnosed with essential hypertension. The patients were referred from Primary Care to the Hypertension and Vascular Risk Unit between January 1, 1998 and August 31, 1999. Blood pressure measurements, blood and urine analysis, and echocardiography were simultaneously performed. They were followed up for 12.5 years (mean [± IQR]: 10.61 [± 3.11] years) and 174 events were recorded.The study included 405 patients (53.8% women), with a mean age of 55.5 years. The estimated glomerular filtration rate according to the MDRD and CKD-EPI equations was 73.9±2.6 mL/min/1.73m(2) and 76.9±2.2 mL/min/1.73m(2), respectively. The prevalence of chronic kidney disease was 31.6% and 23.9%, respectively. Using the CKD-EPI equation led to the re-classification of 22.9% of patients. The incidence rate ratio (IRR [95%CI] for chronic kidney disease identified by the MDRD equation was 2.4 [1.8-3.3], and for the CKD-EPI calculation it was 2.5 [1.8 to 3.3]).Both equations estimate similar magnitudes of renal function, although the CKD-EPI equation has less false positives, and both have similar prognostic values in patients at high cardiovascular risk as well those at low risk.

The tetanus toxin C (TTC) fragment capacity of being transported in a retrograde way through motoneurons and its nontoxic nature opens the door to a new promising therapeutic strategy for neurodegenerative diseases. In this study, the TTC effect was tested for the first time in animal model of global cerebral ischemia induced by 10-min occlusion of both common carotid arteries. The aim was to evaluate the effect of TTC gene therapy treatment on the development and expression of global cerebral ischemia/reperfusion-induced oxidative stress and motor hyperactivity in Mongolian gerbils. Several oxidative stress and motor behavioral parameters were investigated between 2 h and 14 days after reperfusion. Neuroprotective efficiency of TTC was observed in the forebrain cortex, striatum, hippocampus, and cerebellum at the level of each examined oxidative stress parameter (nitric oxide level, superoxide production, superoxide dismutase activity, and index of lipid peroxidation). Additionally, TTC significantly decreased ischemia-induced motor hyperactivity based on tested parameters (locomotion, stereotypy, and rotations). As judged by biochemical as well as behavioral data, treatment with TTC for the first time showed neuroprotective efficiency by reduction of ischemia-induced oxidative stress and motor hyperactivity and can be a promising strategy for ischemia-induced neuronal damage treatment.

Objectives: The aim of this study was to assess the incidence and clinical pattern of celiac disease (CD) presently diagnosed in Spanish children. Methods: A prospective, multicenter, nationwide registry of new cases of CD in children

Sex bias has been described nowadays in biomedical research on animal models, although sexual dimorphism has been confirmed widely under pathological and physiological conditions. The main objective of our work was to study the sex differences in constitutive autophagy in spinal cord and skeletal muscle tissue from wild type mice. To examine the influence of sex on autophagy, mRNA and proteins were extracted from male and female mice tissues. The expressions of microtubule-associated protein 1 light chain 3 (LC3) and sequestosome 1 (p62), markers to monitor autophagy, were analyzed at 40, 60, 90, and 120 days of age. We found significant sex differences in the expression of LC3 and p62 in both tissues at these ages. The results indicated that sex and tissue specific differences exist in constitutive autophagy. These data underlined the need to include both sexes in the experimental groups to minimize any sex bias.

Amyotrophic lateral sclerosis is a neurodegenerative disease associated with mutations in antioxidant enzyme Cu/Zn-superoxide dismutase 1. Albeit there is no treatment for this disease, new insights related to an exacerbated lipid metabolism have been reported. In connection with the hypermetabolic lipid status, the hypothesis whether nature of dietary fat might delay the progression of the disease was tested by using a transgenic mouse that overexpresses the human SOD1G93A variant. For this purpose, SOD1G93A mice were assigned randomly to one of the following three experimental groups: (1) a standard chow diet (control, n=21), (2) a chow diet enriched with 20% (w/w) extra virgin olive oil (EVOO, n=22) and (3) a chow diet containing 20% palm oil (palm, n=20). They received the diets for 8 weeks and the progression of the disease was assessed. On the standard chow diet, average plasma cholesterol levels were lower than those mice receiving the high-fat diets. Mice fed an EVOO diet showed a significant higher survival and better motor performance than control mice. EVOO group mice survived longer and showed better motor performance and larger muscle fiber area than animals receiving palm. Moreover, the EVOO-enriched diet improved the muscle status as shown by expression of myogenic factors (Myod1 and Myog) and autophagy markers (LC3 and Beclin1), as well as diminished endoplasmic reticulum (ER) stress through decreasing Atf6 and Grp78. Our results demonstrate that EVOO may be effective in increasing survival rate, improving motor coordination together with a potential amelioration of ER stress, autophagy and muscle damage.

Genetic susceptibility to celiac disease (CD) is strongly associated with DQA1*0501 and DQB1*02 (= DQ2). To study whether CD patients without DQ2 share other MHC class II or TNF alleles, we screened DQ2-negative patients in Finland and Spain. Twelve of 84 (14%) Finnish patients and 13 of 189 (6%) Spanish patients were negative for DQ2. We observed that all but two of altogether 25 DQ2-negative patients had the DR4 DQ8 haplotype, or either DQA1*0501 or DQB1*02 alone. Also, all but three were positive for DRB4*01. The only patients without any of these alleles were both positive for DR 13. There was a clear difference between Finland and Spain: Ten (83%) of the 12 Finnish DQ2-negative patients but only five (38%) of the 13 Spanish patients had DRB1*03, DQA1*03, DQB1*0302 (= DQ8) alleles. Of the Spanish patients, eight (62%) had DQB1*02 without DQA1*0501 and three (23%) had DQA1*0501 without DQB1*02. None of the TNF, TAP, or DPB1 alleles was found to be significantly associated with CD. Our results indicate that in addition to the DQ2 heterodimer, the other major risk alleles for CD are DR4 DQ8, and either DQA1*0501 or DQB1*02 alone. Patients without these alleles appear to be very rare, only two (0.7%) were identified in altogether 253 patients tested.

This is an open-access article distributed under the terms of the Creative Commons Attribution License., We studied whether celiac disease (CD) patients produce antibodies against a novel gliadin peptide specifically generated in the duodenum of CD patients by a previously described pattern of CD-specific duodenal proteases. Fingerprinting and ion-trap mass spectrometry of CD-specific duodenal gliadin-degrading protease pattern revealed a new 8-mer gliadin-derived peptide. An ELISA against synthetic deamidated 8-mer peptides (DGP 8-mer) was used to study the presence of IgA anti-DGP 8-mer antibodies in plasma samples from 81 children (31 active CD patients (aCD), 17 CD patients on a gluten-free diet (GFD), 10 healthy controls (C) and 23 patients with other gastrointestinal pathology (GP)) and 101 adults (16 aCD, 12 GFD, 27 C and 46 GP-patients). Deamidation of the 8-mer peptide significantly increased the reactivity of the IgA antibodies from CD patients against the peptide. Significant IgA anti-DGP 8-mer antibodies levels were detected in 93.5% of aCD-, 11.8% of GFD- and 4.3% of GP-patients in children. In adults, antibodies were detected in 81.3% of aCD-patients and 8.3% of GFD-patients while were absent in 100% of C- and GP-patients. Duodenal CD-specific gliadin degrading proteases release an 8-mer gliadin peptide that once deamidated is an antigen for specific IgA antibodies in CD patients which may provide a new accurate diagnostic tool in CD. © 2013 Vallejo-Diez et al., This work has been supported by grants (to EA) from the Instituto de Salud Carlos III – FEDER (PI070244, PI10/01647), Junta de Castilla y León (SAN126/VA31/09), AECID (A/019196/08), and Phadia Spain S.L (now ThermoFisher Scientific).

Management of the South American tomato leafminer, Tuta absoluta Meyrick, with insecticides has led to the widespread development of insect resistance. Mass trapping using traps baited with the female-produced sex pheromone is an attractive alternative for the management of this pest. The current study evaluated several commercial trap designs for capture of T. absoluta. Based on its small size and ease of handling, the most effective trap is a small plastic container with entry windows cut on the sides filled with motor oil over water. These traps are most effective when placed near ground level. Tests of septa containing 0.1 or 0.2 mg of the pheromone (95:5) E4, Z8-14Ac/E4,Z8,Z11-14Ac were slightly more attractive than septa loaded with 0.5, 1.0, or 2 mg during the first week of use, but the latter three loadings were slightly more attractive than the first two loadings after 9 weeks. Ideal trap baits were loaded with 0.5 mg of pheromone. Higher numbers of T. absoluta were captured near upwind borders of tomato fields suggesting that treatments against T. absoluta should be concentrated near upwind parts of fields. Comparisons of conventional insecticide treatment versus mass trapping to manage T. absoluta damage in three different test sites showed that even when initial captures in monitoring traps were high (35 males trap(-1) day(-1)), mass trapping at 48 traps/ha reduced leaf damage more efficiently than conventional insecticide treatment. Based on the typical insecticide recommendations against T. absoluta, mass trapping is an economically viable alternative.

There are currently several national guidelines on the appropriate empirical use of antibiotics in Spanish children. But, do the Spanish paediatricians use these guidelines when prescribing antimicrobials?A national study from was conducted from April to June 2012 using an on-line questionnaire on the empirical selection of antibiotics in children. An e-mail was sent to paediatrician members of the Spanish Association of Paediatrics (AEP) or its Regional or Paediatric Specialties Societies. Current guidelines and consensus documents were used to determine the appropriateness of the responses.A total of 1214 responses were received. Eighty five per cent of the treatments selected by Spanish paediatricians were adjusted to guidelines. The least appropriate responses were obtained in those infectious diseases with no national consensus document at the time of the survey (73% in this case).Spanish paediatricians mainly select empirical antibiotics in accordance with current guidelines. However, there are features that could be improved in our country. The preparing and implementation of national consensus documents on the management of paediatric infectious diseases should be continued. We propose to regularly perform these kinds of surveys, including real prescription studies, and to also extend it to other paediatric specialities, in order to promote appropriateness of use of all the paediatric drugs in our country.

Purpose and background Amyotrophic lateral sclerosis (ALS) is a progressive, fatal neurodegenerative disease with no effective therapy. Glial-cell line derived neurotrophic factor (GDNF) has been translated to clinical trials for treatment of ALS and its selective delivery to the motoneurons could improve its therapeutic abilities. Methods To test this idea, we genetically fused GDNF to the C-fragment of tetanus toxin (TTC), a peptide able to specifically deliver molecules to motoneurons. Results Single intramuscular administration of naked-DNA encoding GDNF or GDNF-TTC significantly delayed the onset of symptoms and functional deficits into the SODG93A mouse model of ALS, prolonging their lifespan. Conclusions We have demonstrated a neuroprotective effect of GDNF-TTC as shown by the activation of survival pathways and inhibition of apoptotic proteins, such as Akt phosphorylation, or reduced caspase-3 activation respectively. However, the GDNF fusion with TTC did not improve the therapeutic effects when compared to GDNF alone.

During postnatal growth and after muscle injury, satellite cells proliferate and differentiate into myotubes to form and repair musculature. Comparison of studies on satellite cell proliferation and differentiation characteristics is confounded by the heterogeneity of the experimental conditions used. To examine the influence of sex, age, and fiber-type origin on in vitro properties of satellite cells derived from postnatal muscles, fast extensor digitorum longus (EDL) and slow soleus (SOL) muscles were extracted from male and female mice of 1 week to 3 months of age. Myoblast proliferation and myogenic regulatory factor (MRF) expression was measured from cultures of freshly isolated satellite cells. Higher proliferation rate and elevated Myod1 expression was found in male EDL and SOL derived cells compared with females at age of 40, 60, and 120 days, whereas inverse tendency for cell proliferation was apparent in EDL of juvenile (7-day-old) pups. Myogenin and Mrf4 transcripts were generally elevated in males of 40 and 60 days of age and in female EDL of juveniles. However, these differentiation markers did not significantly correlate with proliferation rate at all ages. Pax7, whose overexpression can block myogenesis, was up-regulated especially in 40-day-old females where MRF expression was low. These results indicate that gender, postnatal age, and muscle fiber origin affect proliferation and muscle transcription factor expression in vitro. The results also support the view that satellite cells originating from slow and fast muscles are intrinsically different and warrant further studies on the effect of cell origin for therapeutic approaches.

Reliability and accuracy of real-time quantitative PCR results depend on the use of housekeeping genes which must be constitutively expressed thorough the samples of the study. In the present work, we tested the expression stability of six candidate housekeeping genes (Actb, Rn18s, Gapdh, Hprt1, Sdha and B2m) considering sex, age, muscle-type and neurodegeneration or denervation status in mouse muscle satellite cells. Their expression varied under all variables tested; therefore the ranking of the most suitable genes for the normalization is modified depending on the factors included in the analysis, especially the age of the donor. Moreover, we describe the unsuitability of Rn18s in analysis comprising samples of different ages. On the other hand, we demonstrate that the use of the two best genes in each case is enough to obtain a reliable normalization factor. In this work, we give a broad information of the best housekeeping genes in mouse myogenic cells depending on the variables included in the experimental design.

Statistical, spectral, multi-resolution and non-linear methods were applied to heart rate variability (HRV) series linked with classification schemes for the prognosis of cardiovascular risk. A total of 90 HRV records were analyzed: 45 from healthy subjects and 45 from cardiovascular risk patients. A total of 52 features from all the analysis methods were evaluated using standard two-sample Kolmogorov-Smirnov test (KS-test). The results of the statistical procedure provided input to multi-layer perceptron (MLP) neural networks, radial basis function (RBF) neural networks and support vector machines (SVM) for data classification. These schemes showed high performances with both training and test sets and many combinations of features (with a maximum accuracy of 96.67%). Additionally, there was a strong consideration for breathing frequency as a relevant feature in the HRV analysis.

Background Amyotrophic lateral sclerosis (ALS) is one of the most devastating neurodegenerative diseases. Neurotrophic factors have been widely tested to counteract neurodegenerative conditions, despite their unspecific neuronal access. The non-toxic C-terminal fragment of the tetanus toxin (TTC) heavy chain has been studied not only as a carrier molecule to the CNS but also as a neuroprotective agent. Because the neurotrophic effects of BDNF have been demonstrated in vitro and in vivo, the question addressed in this work is whether a fusion molecule of BDNF-TTC may have a synergistic effect and enhance the neuroprotective properties of TTC alone in a mouse model of ALS. Methods Recombinant plasmid constructs (pCMV-TTC and pCMV-BDNF-TTC) were injected into the quadriceps femoris and triceps brachialis muscles of SOD1G93A transgenic mice at 8 weeks of age. The hanging wire and rotarod tests were performed to assess motor coordination, strength and balance. Electrophysiological tests, morphological assays of spinal cord sections of L2 and L4 segments, and gene and protein expression analyses were performed. The Kaplan-Meier survival analysis test was used for comparisons of survival. Multiple comparisons of data were analyzed using a one-way analysis of variance (ANOVA). Results Treatment with the fusion-molecule BDNF-TTC and with TTC alone significantly delayed the onset of symptoms and functional deficits of SOD1G93A mice. Muscle innervation was partially preserved with these treatments, and the number of surviving motoneurons in L2 spinal cord segment was increased particularly by the fusion protein induction. Inhibition of pro-apoptotic protein targets (caspase-3 and Bax) and significant phosphorylation of Akt and ERK were also found in the spinal cord of treated mice. Conclusions Significant improvements in behavioral and electrophysiological results, motoneuron survival and anti-apoptotic/survival-activated pathways were observed with BDNF-TTC treatment. However, no synergistic effect was found for this fusion molecule. Although BDNF in the fusion molecule is capable of activating autocrine and neuroprotective pathways, TTC treatment alone yielded similar neuroprotection. Therefore, an accurate study of the neuroprotective effects of TTC fusion molecules should be performed to obtain a better understanding of its effects.

To compare the resting energy expenditure (REE) and the REE/Fat-free-mass (FFM) quotient in children with constitutional leanness (CL) and children with normal body weight, and to describe the within-family clustering of CL.We have studied 18 children and teenagers with CL, 10 girls and 8 boys, and 18 gender and age matched normal controls, with the same pubertal stage. All were recruited from the outpatient pediatric clinic nutrition unit. None of the children with CL showed symptoms of chronic illness, they had normal laboratory results, they had a normal caloric food intake, and they did not agree with the DSM-IV-TR criteria for anorexia nervosa. We describe the body mass index (BMI) of children and their parents. The children were classified according to Cole's recently published BMI cut-offs for thinness: under 18.5 points in CL group, stable at least in the last year, and between 18.5 and 25 cutt-offs in the control group. The body composition was calculated by anthropometric methods (skinfold thickness measurements). In addition REE was measured using fasting indirect calorimetry.The CL group had a higher mean percentage of FFM, and a mean FM significantly less, relative to controls (p0.001). The average absolute REE was significantly lower in the CL group (1,106.55 ± 240.72 kcal) than the control group (1,353.33 ± 270.01 kcal/dia) (p0.01). However, the REE adjusted for FFM showed a mean significantly greater in the CL group (41.39 ± 2.26 kcal/kg FFM) (Mean confidence interval (CI) 95 %: 40.33-42.45) than the controls (37.37 ± 3.06 kcal/kg FFM) (Mean CI 95 %: 35.93-38.81) (p0.001). Finally, in the family study, the mean BMI of fathers of CL group was significantly lower (p0.01), but there were not any differences in the mean BMI of mothers. Among parents with BMI known, 8 of 35 parents of CL group had an BMI lower 18.5, and only 2 of 36 parents in the control group (p0.05).This increased energy expenditure-to-FFM ratio differentiates between CL and controls. These metabolic differences are probably genetically determined.

Multiple endocrine neoplasia syndrome, type 2B (MEN 2B), is a rare entity characterized by the presence of medullary thyroid cancer in 100% of the cases. The phenotype of this syndrome consists in the presence of marfanoid features and mucocutaneous neuromas. We describe the case of a male patient with MEN 2B syndrome who was diagnosed with medullary thyroid cancer after lung metastases was found. We analyze the role of DMSA-V and the new hybrid SPECT-CT scan systems in the extension study and monitoring of medullary thyroid cancer.

A 25 year old patient with high myopia diagnosed of metachronic choroidal neovascularisation in both eyes secondary to punctate inner choroidopathy leading to visual impairment and metamorphopsia. First eye was treated with four injections of ranibizumab after photodynamic therapy and the second eye only with charge dose of ranibizumab, reaching inactivity with good final visual acuity in both eyes.Ranibizumab is useful in the treatment of this illness. Prospective studies are needed to investigate the usefulness of a combination with adjuvant therapies such as photodynamic therapy.

Beradinelli-Seip congenital generalized lipodystrophy is a rare autosomal recessive disorder characterized by near-complete absence of adipose tissue, Herculean appearance, insulin resistance, hypoleptinaemia and diabetes mellitus. The aim of this study was to investigate the in vitro effects of pioglitazone on the expression of genes involved in adipogenesis in fibroblasts from a patient with this condition due to a seipin mutation.Primary cultures of fibroblasts from the skin of the patient were obtained. Fibroblasts were treated with classic adipose differentiation medium, with and without pioglitazone. Several adipogenes were evaluated by real-time reverse transcriptase-polymerase chain reaction and western blotting. Intracellular localization of prelamin A was studied by immunofluorescence microscopy.The expression of the adipogenic genes PPARG, LPL, LEP and SLC2A4 was reduced in lipodystrophic fibroblasts, while treatment with pioglitazone increased the expression of these genes. Moreover, and unexpectedly, we found an accumulation of farnesylated prelamin A in lipodystrophic fibroblasts.The process of adipocyte differentiation is compromised in patients with Beradinelli-Seip congenital lipodystrophy owing to diminished expression of the regulatory genes involved, which pioglitazone treatment partially rescues. Prelamin A accumulation establishes a link with other types of familial lipodystrophies, as familial partial lipodystrophy.

Background: In the superoxide dismutase 1 (SOD1)-G93A mouse model of amyotrophic lateral sclerosis (ALS), skeletal muscle is a key target of mutant SOD1 toxicity. However, the expression of factors that control the regenerative potential of the muscle is unknown in this model. Objective: To characterize the expression of satellite cell marker Pax7 and myogenic regulatory factors (MRF) in skeletal muscle of SOD1-G93A mice at different stages of the disease. Methods: The expressions of Pax7, Myod1, Myf5 and myogenin (Myog) were determined by quantitative real-time PCR and by Western blotting from the grouped gastrocnemius, quadriceps and soleus muscles of SOD1-G93A mice at presymptomatic, symptomatic and terminal stages of the disease, and from surgically denervated wild-type gastrocnemius muscles. Results:Pax7 mRNA and MYF5 protein were upregulated in presymptomatic mice, coinciding with increased muscle damage marker Rrad and chemokine Ccl5. All MRF transcripts and most proteins (excluding MYOG) were increased, starting from 3 months of age, simultaneously with increased expression of denervation marker Chrna1. However, in the terminal stage, no protein increase was evident for Pax7 or any of the MRF despite the increased mRNA levels. The transcripts for chemokine Ccl2 and chemokine receptor Cxcr4 were increased starting from the onset of symptoms. Conclusions: The characterization of Pax7 and MRF in SOD1-G93A mice reveals a progressive induction of the myogenic program at the RNA level, but a blunted protein level response at late stages of the disease. Altered posttranscriptional and posttranslational mechanisms likely to operate, as well as the potential role of chemokine signaling in mutant SOD1 muscle, are discussed.

We present the case of a 60-year old male with a follicular pattern of multifocal invasive papillary thyroid carcinoma who had undergone total thyroidectomy. During post-surgical follow-up with I-131 scan, a I-131 deposit was observed in the upper left hemiabdomen. Due to suspicion that it could be a metastasis, an ultrasound and CT scan were performed, with the subsequent diagnosis of a left simple serous renal cyst. Once confirmed, drainage was performed under ultrasound control, obtaining I-131 in the analysis of its content.

Background Acute wheezing episodes are frequently associated with respiratory viral infections in children. However, the role of the recently described respiratory viruses is not yet fully understood. Objective The main objective of this study was to estimate the frequency of human metapneumovirus (HMPV), human bocavirus (HBoV), and 14 other respiratory viruses in hospitalized children with acute wheezing. Methods A prospective study was conducted on children

To evaluate the nutritional status of the elderly hospitalized patient with the Mini Nutritional Assessment (MNA), its relationship with length of hospital stay and mortality, the incidence of malnutrition during hospitalization and to evaluate the applicability of MNA in an Internal Medicine Department of an acute care hospital.A prospective study on the nutritional status of patients of 65 years or older admitted to hospital in an Internal Medicine Department was performed in 106 consecutive patients. In all patients a MNA test, an anthropometric (weight, height, body mass index, skinfold), and biochemical (cholesterol, lymphocytes, albumin) evaluation were performed; outcome, age, institutionalization, Charlson index and Barthel index were recorded.Mean age of the patients was 81±7 years, Charlson index 2.3±1.9 and Barthel index 74.9±30.8. Mean weight was 64.5±10.6kg, BMI 26±3.9, and weight loss in the previous 3 months 1.17±2.92kg. Mean length of hospital stay was 11.1±9.8, and mortality was 5.7%. Prevalence of malnutrition, assessed by MNA, was 4.7%, and 36.8% of the patients were at risk of malnutrition. Malnourished patients have a longer length of hospital stay, higher Barthel and Charlson indexes. There are no conclusive differences in mortality. Incidence of malnutrition during hospitalization was between 2.43 and 15.68%.Malnutrition increases length of hospital stay, rate of complications and costs. The clinicians responsible for the patient should perform nutrition evaluation at hospital admission and repeat it during the hospitalization, using simple screening tools that incorporate an explicit nutrition intervention plan.

PubMedID: 19196360 Aims: To demonstrate the benefit of the combination amlodipine/valsartan 5/160 mg over amlodipine 10 mg, in producing a lower incidence of peripheral oedema for a comparable mean sitting systolic blood pressure (MSSBP) reduction. Methods: After a 4-week amlodipine 5 mg run-in phase, inadequately controlled hypertension patients (aged ? 55 years, MSSBP ? 130 and ? 160 mmHg) were randomised to receive amlodipine/valsartan 5/160 mg or amlodipine 10 mg for 8 weeks, followed by amlodipine/valsartan 5/160 mg for 4 weeks for all patients. Primary variables were MSSBP change from baseline to week 8 and incidence of peripheral oedema reported as an AE. Resolution of peripheral oedema was assessed 4 weeks after switching patients from amlodipine 10 mg to amlodipine/ valsartan 5/160 mg. Results: At week 8, MSSBP showed greater reduction with amlodipine/valsartan 5/160 mg than amlodipine 10 mg (least square mean: -8.01 vs.-5.95 mmHg, p < 0.001 for non-inferiority and p = 0.002 for superiority). Systolic control, overall BP control and systolic response rate at week 8 were significantly higher with combination than amlodipine 10 mg (34 vs. 26%; 57 vs. 50%; 36.57 vs. 27.77%, respectively). Incidence of peripheral oedema was significantly lower with the combination than amlodipine 10 mg (6.6 vs. 31.1%, p < 0.001). Peripheral oedema resolved in 56% patients who switched from amlodipine 10 mg to the combination, without the loss of effect on BP reduction. Conclusion: In non-responders to amlodipine 5 mg, treatment with amlodipine/valsartan 5/160 mg induced significantly less peripheral oedema than amlodipine 10 mg for similar BP reduction. Peripheral oedema resolved in > 50% patients switching from amlodipine 10 mg to the combination. © 2009 The Authors.Indications:671 patients with refractory essential hypertension. Coexisting disease was diabetes mellitus in 486 patients.Patients:1183 patients. Exforge group: n=592, 307 males and 285 females, mean age 65.6 years; 559 Caucasian and 33 other; 35 dropouts, 14 were due to side effects. Amlodipine 10 mg group: n=591, 307 males and 284 females, mean age 65.4 years; 560 Caucasian, 28 other, 2 Asian and 1 Pacific Islander; 115 dropouts, 84 were due to side effects. Amlodipine switched to Exforge at week 8 group (switched group): n=484.TypeofStudy:A study evaluating the non-inferiority of Exforge compared with amlodipine 10 mg with respect to antihypertensive efficacy, along with the incidence of peripheral edema, in patients with essential hypertension not adequately controlled with amlodipine 5 mg alone. A randomized, multicenter, placebo-controlled, single-blind study for 4 weeks and double blind-study for 12 weeks.DosageDuration:Amlodipine 5 mg and valsartan 160 mg once daily in the morning. Duration was 4-12 weeks.ComparativeDrug:Amlodipine was given at 10 mg once daily in the morning. Duration was 8 weeks.Results:The frequency of discontinuation due to AEs was higher in the amlodipine group (14.2%) vs. Exforge group (2.5%). The least square mean (LSM) reduction of MSSBP with the Exforge group was statistically non-inferior compared with amlodipine group. Non-inferiority was also observed with LSM reductions from baseline at week 4 and 8 in MSSBP and week 8 in MSDBP and at week 12 after the switch from amlodipine to Exforge. The systolic control produced by Exforge was better than amlodipine alone at week 4 and 8, and similar after the switch from amlodipine to Exforge. Overall BP control was attained in a significantly higher proportion of patients in the Exforge group at weeks 4 and 8. The systolic BP response rate was higher with Exforge vs. amlodipine 10 mg at week 4 and 8, and similar after the switch from amlodipine 10 mg to Exforge at week 12. The most frequently reported adverse event (AE) during the study was peripheral edema, which was higher in the amlodipine 10 mg group (31.5%) vs. the Exforge group (7.3%). The severity of peripheral edema was also higher in the amlodipine group vs. the Exforge group. Exforge induced significantly less peripheral edema than amlodipine 10 mg up to and including week 8. The incidence of peripheral edema decreased in both groups from week 8 to 12 (more pronounced in the switched group than in the group that remained on Exforge. Resolution of peripheral edema was observed in more than half of the patients (44 out of 79) after they were switched to Exforge. Resolution of peripheral edema at week 12 was higher in the switched group vs. Exforge group. Both regimens were well tolerated. The overall incidence of AEs was higher in the amlodipine group (55.7%) vs. the Exforge group (43.9%). The second most frequently reported AE was headache (3.2% amlodipine group vs. 2.2% Exforge group). The most frequently reported AE leading to discontinuation was peripheral edema (1% Exforge vs. 11.5% amlodipine), followed by headache (0.2% Exforge vs. 0.5% amlodipine).AdverseEffects:36 and 35 patients in the Exforge group and Switched group, respectively had peripheral edema leading to withdrawal in 5 Exforge-treated patients. 13 Exforge-treated patients had headache leading to withdrawal in 1.AuthorsConclusions:In those hypertensive patients not adequately responding to amlodipine 5 mg monotherapy, the combination of amlodipine/valsartan 5/160 mg induces significantly lesser peripheral oedema for similar BP reductions, and a better safety and tolerability profile than amlodipine 10 mg. In addition, in patients experiencing oedema in the high-dose amlodipine monotherapy arm, more than half resolved after switching to amlodipine/valsartan 5/160 mg. Thus, an effective alternative to amlodipine dose escalation in patients would be a combination of low-dose amlodipine and valsartan, which has a better antihypertensive effect than high-dose amlodipine and a better tolerability profile.FreeText:The mean sitting systolic BP (MSSBP) of all patients was not adequately controlled by amlodipine 5 mg alone and were switched to Exforge or amlodipine 10 mg alone for 8 weeks. At week 8, patients on Exforge continued the same treatment while those on amlodipine 10 mg alone switched to the Exforge group for an additional 4 weeks of treatment. Blood pressure (BP) was monitored (MSSBP and mean sitting diastolic BP [MSDBP]). The occurrence of peripheral edema was assessed.

Tyrosine hydroxylase (TH) is the rate-limiting enzyme in the synthesis of catecholamine neurotransmitters. Primary inherited defects in TH have been associated with l-DOPA responsive and non-responsive dystonia and infantile parkinsonism. In this study, we show that both the cofactor (6R)-l-erythro-5,6,7,8-tetrahydrobiopterin (BH(4)) and the feedback inhibitor and catecholamine product dopamine increase the kinetic stability of human TH isoform 1 in vitro. Activity measurements and synthesis of the enzyme by in vitro transcription-translation revealed a complex regulation by the cofactor including both enzyme inactivation and conformational stabilization. Oral BH(4) supplementation to mice increased TH activity and protein levels in brain extracts, while the Th-mRNA level was not affected. All together our results indicate that the molecular mechanisms for the stabilization are a primary folding-aid effect of BH(4) and a secondary effect by increased synthesis and binding of catecholamine ligands. Our results also establish that orally administered BH(4) crosses the blood-brain barrier and therapeutic regimes based on BH(4) supplementation should thus consider the effect on TH. Furthermore, BH(4) supplementation arises as a putative therapeutic agent in the treatment of brain disorders associated with TH misfolding, such as for the human TH isoform 1 mutation L205P.

To determine the efficacy of Photodynamic Therapy (PDT) in chronic Central Serous Chorioretinopathy (CSC).Patients diagnosed with chronic CSC, with clinical evidence of activity and treated with Photodynamic Therapy, are included in this report. All were assessed by a complete ophthalmological examination, including assessment of the best corrected visual acuity (BCVA) using an ETDRS chart, fluorescein and indocyanine angiography and optical coherence tomography (OCT). The main objective of the study was to determine the mean visual acuity change.11 eyes of 11 patients were included in the study, which had a mean follow-up period of 11 months. The mean BCVA increased from 20/76 to 20/64. 35% of eyes improved their BCVA by 2 lines or more, 45% remained stable and 18% lost 2 lines or more. Choroidal hyperpermeability was reduced in every case. Neurosensorial retinal detachment decreased in 80% of cases. Only one eye received a second PDT treatment due to choroidal neovascularization. An increase of atrophy over the Retinal Pigment Epithelium (RPE) was observed in another patient.PDT can reduce the clinical signs of activity, such as choroidal hyperpermeability or neurosensorial retinal detachment, in patients affected by chronic CSC. However, the increase in visual acuity is variable, probably due to the extent of RPE damage.

The IL-15 triggering effect of gliadin is not exclusive to coeliac disease (CD) patients, whereas the secondary response is CD specific. We have studied the expression of the IL-15 receptor, and the IL-15 response upon stimulation, in non-CD and CD patients, and the possible existence of a lower immunological threshold in the latter. Forty-two CD patients (20 on a gluten-containing diet, GCD, and 22 on gluten-free diet, GFD) and 24 non-CD healthy individuals were studied. IL15Rα mRNA expression, and tissue characterization, were assayed in the duodenum. Biopsies from six CD patients on GFD and 10 non-CD individuals were studied in vitro using organ culture in basal conditions, as well as after IL-15 stimulation discarding basal IL-15 production. Secretion of immune mediators was measured in the culture supernatants. IL15Rα mRNA expression was increased in CD patients, as compared with non-CD controls (on GFD P = 0.0334, on GCD P = 0.0062, respectively), and confirmed also by immunofluorescence. No differences were found between CD patients on GFD and on GCD. After in vitro IL-15 stimulation, IL15Rα expression was only triggered in non-CD controls (P = 0.0313), though it remained increased in CD patients. Moreover, IL-15 induced a more intense immunological response in CD patients after triggering the production of both nitrites and IFNγ (P = 0.0313, P = 0.0313, respectively). Gliadin-induced IL15 has a lower response threshold in CD patients, leading to the production of other immune mediators and the development of the intestinal lesion, and thus magnifying its effects within the CD intestine. © 2008 British Society for Immunology., This work has been partially funded by the Spanish Ministry of Education (FPU, AP2002-2696), Spanish Ministry of Health (PI070244; 02/3068), Junta de Castilla y León (VA089/06, SAN196-VA17/07) and Asociación de Celiacos de Madrid (ACM).

Hemodiafiltration (HDF) is a technique resulting from coupling of diffusive and convective transport and thereby increase the elimination of small and middle molecules. However, may induce a convective loss from others substances such as calcium and magnesium. The aim of this study was to evaluate the effects of Ultrafiltration on the kinetics of calcium, phosphate, magnesium and parathyroid hormone. A total of thirteen patients (7 males and 6 females) on hemodialysis, were studied. Each patient was randomly dialyzed with the same dialysate calcium concentration and three different ultrafiltration rate. Schedule A: High flux hemodialysis, schedule B: HDF with 10% of weight body and schedule C: HDF with 20% of weight body. The others parameters were kept identical. Total Ultrafiltration was 2,6+/-0,9 L (9,78+/-3,78 ml/min) in A, 9,3+/-1,7 L (34,54+/-6,22 ml/min) in B and 16,3+/-3,3 L (60,94+/-12,63 ml/min) in C. Replacement fluid during dialysis was 6,85+/-1,42 and 13,65+/-2,9 L. in C and C respectively. Postdialysis total,ionized calcium and magnesium were significantly lower in schedules B and C versus A. PTH levels did not differ significantly. However, PTH changes during dialysis was -36.6+/-38.6%, 6.3+/-69.8% and 32.2+/-63.2% in A, B and C, respectively (p0.05 A vs. C). A significant inverse correlation was found between total Ultrafiltration and postdialysis levels of total calcium (r:-0.56, p0.001), ionized calcium (r:-0.65, p0.001) and magnesium (r:-0.47, p0.01). No differences were observed in pre and postdialysis phosphate levels, neither mass transfer and clearance of phosphate. We concluded that high ultrafiltration flow rates and substitution fluid without divalent cations induces a negative calcium and magnesium balance. These changes may stimulate PTH secretion during HDF. This technique did not resulted in a higher clearance or phosphate removal.