The impact of exposure to tobacco smoke and e-cigarettes on asthma-related outcomes: Systematic review informing the EAACI guidelines on environmental science for allergic diseases and asthma.

To inform the clinical practice guidelines' recommendations developed by the European Academy of Allergy and Clinical Immunology systematic reviews (SR) assessed using GRADE on the impact of environmental tobacco smoke (ETS) and active smoking on the risk of new-onset asthma/recurrent wheezing (RW)/low lung function (LF), and on asthma-related outcomes. Only longitudinal studies were included, almost all on combustion cigarettes, only one assessing e-cigarettes and LF. According to the first SR (67 studies), prenatal ETS increases the risk of RW (moderate certainty evidence) and may increase the risk of new-onset asthma and of low LF (low certainty evidence). Postnatal ETS increases the risk of new-onset asthma and of RW (moderate certainty evidence) and may impact LF (low certainty evidence). Combined in utero and postnatal ETS may increase the risk of new-onset asthma (low certainty evidence) and increases the risk of RW (moderate certainty evidence). According to the second SR (24 studies), ETS increases the risk of severe asthma exacerbations and impairs asthma control and LF (moderate certainty evidence). According to the third SR (25 studies), active smoking increases the risk of severe asthma exacerbations and of suboptimal asthma control (moderate certainty evidence) and may impact asthma-related quality-of-life and LF (low certainty evidence).

A Pluto-like radius and a high albedo for the dwarf planet Eris from an occultation.

The dwarf planet Eris is a trans-Neptunian object with an orbital eccentricity of 0.44, an inclination of 44 degrees and a surface composition very similar to that of Pluto. It resides at present at 95.7 astronomical units (1 AU is the Earth-Sun distance) from Earth, near its aphelion and more than three times farther than Pluto. Owing to this great distance, measuring its size or detecting a putative atmosphere is difficult. Here we report the observation of a multi-chord stellar occultation by Eris on 6 November 2010 UT. The event is consistent with a spherical shape for Eris, with radius 1,163 ± 6 kilometres, density 2.52 ± 0.05 grams per cm(3) and a high visible geometric albedo, Pv = 0.96(+0.09)(-0.04). No nitrogen, argon or methane atmospheres are detected with surface pressure larger than ∼1 nanobar, about 10,000 times more tenuous than Pluto's present atmosphere. As Pluto's radius is estimated to be between 1,150 and 1,200 kilometres, Eris appears as a Pluto twin, with a bright surface possibly caused by a collapsed atmosphere, owing to its cold environment. We anticipate that this atmosphere may periodically sublimate as Eris approaches its perihelion, at 37.8 astronomical units from the Sun.

Assessment of the current and emerging criteria for the histopathological classification of lung neuroendocrine tumours in the lungNENomics project.

BACKGROUND: Six thoracic pathologists reviewed 259 lung neuroendocrine tumours (LNETs) from the lungNENomics project, with 171 of them having associated survival data. This cohort presents a unique opportunity to assess the strengths and limitations of current World Health Organization (WHO) classification criteria and to evaluate the utility of emerging markers. PATIENTS AND METHODS: Patients were diagnosed based on the 2021 WHO criteria, with atypical carcinoids (ACs) defined by the presence of focal necrosis and/or 2-10 mitoses per 2 mm2. We investigated two markers of tumour proliferation: the Ki-67 index and phospho-histone H3 (PHH3) protein expression, quantified by pathologists and automatically via deep learning. Additionally, an unsupervised deep learning algorithm was trained to uncover previously unnoticed morphological features with diagnostic value. RESULTS: The accuracy in distinguishing typical from ACs is hampered by interobserver variability in mitotic counting and the limitations of morphological criteria in identifying aggressive cases. Our study reveals that different Ki-67 cut-offs can categorise LNETs similarly to current WHO criteria. Counting mitoses in PHH3+ areas does not improve diagnosis, while providing a similar prognostic value to the current criteria. With the advantage of being time efficient, automated assessment of these markers leads to similar conclusions. Lastly, state-of-the-art deep learning modelling does not uncover undisclosed morphological features with diagnostic value. CONCLUSIONS: This study suggests that the mitotic criteria can be complemented by manual or automated assessment of Ki-67 or PHH3 protein expression, but these markers do not significantly improve the prognostic value of the current classification, as the AC group remains highly unspecific for aggressive cases. Therefore, we may have exhausted the potential of morphological features in classifying and prognosticating LNETs. Our study suggests that it might be time to shift the research focus towards investigating molecular markers that could contribute to a more clinically relevant morpho-molecular classification.

Microscopic lesions and modulation of gene expression in cervical medulla during BoAHV-1and BoAHV-5 infection: A mini-review.

Bovine herpesvirus (BoAHV) types 1 and 5 are closely-related neurotropic alpha-herpesviruses. BoAHV-1 generally causes respiratory and genital disease but can occasionally cause encephalitis. BoAHV-5 is the causative agent of non suppurative meningoencephalitis in calves. During neuroinvasion, both viruses reach the central and peripheral nervous system. While brain alterations are well-described, the changes that occur in the medulla have not been fully detailed. In this work, we integrated and analyzed the virological findings, the microscopic lesions and the changes that occur in the expression of genes related to the innate immunity, cell cycle and apoptosis in the cervical medulla of calves experimentally-infected with BoAHV-1 and BoAHV-5. This will contribute to the understanding of the differential neuropathogenesis of these alpha-herpesviruses of cattle.

Sequential use with imiquimod and surgery in extramammary Paget's disease.

Extramammary Paget's disease is an uncommon intraepithelial adenocarcinoma which occurs in areas rich in apocrine glands. Although surgery is the treatment of choice, numerous noninvasive treatments have been tried. There are studies that have demonstrated the efficacy of imiquimod to treat Extramammary Paget's disease, but we found no mention in the literature of its use as neoadjuvant therapy previous to surgery excision. We present a case of a large plaque of extramammary Paget's disease successfully treated with imiquimod and minor surgery of the residual disease.

Severe sorafenib-induced hand-foot skin reaction.

Sorafenib is a new drug, multikinase inhibitor, which has been recently approved for the treatment of metastatic renal cell carcinoma and hepatocellular carcinoma. Up to 90 percent of patients receiving this drug have been reported to develop dermatological symptoms. Recently, it has been suggested that the appearance of skin toxicity during therapy may indicate antitumor activity. We report a new case of sorafenib-induced severe hand-foot skin reaction, which hindered the patient's normal life. The reaction was successfully treated with topical costicosteroids and discontinuation of sorafenib. However, the patient died one month later.

[Usefulness of skin-prick tests in children with hand eczema: comparison with their use in childhood and adult eczema]. / Utilidad de las pruebas epicutáneas en el eczema de manos en niños: estudio comparativo con el eczema en la edad pediátrica y con el eczema de manos en adultos.

BACKGROUND: Hand eczema is not uncommon in children but it is rarely studied using skin-prick tests. Few reports have addressed their usefulness in children and none has specifically analyzed their use in children with hand eczema. MATERIAL AND METHODS: We performed a retrospective study of all children up to 16years of age with hand eczema who were assessed in the Department of Dermatology at Hospital General Universitario in Alicante, Spain with the standard GEIDAC panel over a 5-year period. We compared the epidemiologic data and results of skin-prick tests in this group with those obtained in children with eczema at any site and in adults with hand eczema. RESULTS: The study included a total of 1695 patients: 141 (8.3%) children and 1533 (91.7%) adults. Hand eczema was diagnosed in 496 (31.9%) adults and 32 (22.7%) children. Positive results were obtained in skin-prick tests in 50% of children with hand eczema compared with 37.6% of children with eczema at any site and 50.6% of adults with hand eczema. The current relevance of the positive allergens found in children with hand eczema (76.2%) was greater than that observed in children with eczema at any site (61%) or in adults with hand eczema (43%). The most common allergens in children with hand eczema were kathon CG and fragrance mix I, whereas in the other 2 groups metals were the most common. The most common final diagnosis in children with hand eczema was allergic contact dermatitis (34.3%), which proved to be more common than atopic dermatitis. CONCLUSIONS: We recommend the use of skin-prick tests in all children with chronic hand eczema.

Neuroimmunological interactions in stroke. / Interacciones neuroinmunológicas en el ictus.

INTRODUCTION: Stroke is one of the leading causes of death in the world; its incidence is increasing due to increased life expectancy. However, treatment options for these patients are limited since no clinically effective drugs have been developed to date. DEVELOPMENT: According to clinical evidence, a number of neurochemical changes take place after stroke, including energy depletion, increased free radical synthesis, calcium accumulation, neurotransmitter imbalance, excitotoxicity, and, at a later stage, immune system activation leading to inflammation. Immune response has been shown to be a major factor in disease progression. The release of proinflammatory cytokines such as TNF increase brain damage secondary to excitotoxicity and calcium accumulation, and promote free radical synthesis and cell death through various mechanisms. On the other hand, certain anti-inflammatory cytokines, such as IL-10 and IL-4, have been shown to have a neuroprotective effect and even promote neurogenesis and synapse remodeling, which makes immune modulation a promising treatment approach. CONCLUSIONS: Understanding the relationship between the immune system and the nervous system not only deepens our knowledge of stroke but also provides new diagnostic, prognostic, and therapeutic strategies that may increase the quality of life of stroke patients.

A giant exoplanet orbiting a very-low-mass star challenges planet formation models.

Surveys have shown that super-Earth and Neptune-mass exoplanets are more frequent than gas giants around low-mass stars, as predicted by the core accretion theory of planet formation. We report the discovery of a giant planet around the very-low-mass star GJ 3512, as determined by optical and near-infrared radial-velocity observations. The planet has a minimum mass of 0.46 Jupiter masses, very high for such a small host star, and an eccentric 204-day orbit. Dynamical models show that the high eccentricity is most likely due to planet-planet interactions. We use simulations to demonstrate that the GJ 3512 planetary system challenges generally accepted formation theories, and that it puts constraints on the planet accretion and migration rates. Disk instabilities may be more efficient in forming planets than previously thought.

[Gastrointestinal stromal tumors - a retrospective study of 43 cases]. / Tumores del estroma gastrointestinal. Estudio retrospectivo de 43 casos.

BACKGROUND: gastrointestinal stromal tumors (GISTs) are rare (10 to 20/million). They exist in the whole digestive system and its surroundings, and are most common in the stomach (70%), followed by the small intestine (20-25%), colon and rectum (5%), and esophagus ( < 5%). Their clinical presentation varies from small, incidentally found nodules to large and aggressive tumors. Nowadays GISTs are classified according to Fletcher s classification. OBJECTIVE: to review the features of our GIST population. METHODS: a retrospective study of GIST patients identified by immunohistochemical criteria, from 1997 to December 2007, and classified according to Fletcher s criteria. RESULTS: 43 patients were included (24 men, 19 women) with a mean age of 62.7 years. Gastric GISTs (20 cases, 46.5%), small intestine GISTs (18 cases, 41.9%); in 5 cases metastases of occult tumors were found. Eighteen cases had no symptoms. Tumors were classified according to Fletcher s criteria as high-risk (n = 19), intermediate-risk (n = 7), low-risk (n = 12), and indeterminate-risk (n = 5). Death occurred in 10 patients, and 13 patients had metastatic disease. CONCLUSIONS: our results are in accordance with the world literature, in which a majority of cases are men with gastric tumors. The 5-year survival rate was 42%. Fletcher s criteria were easily applicable criteria and could predict tumor behavior.

Endometrial cancer in polyps: a clinical study of 27 cases.

PURPOSE OF INVESTIGATION: To review risk factors, clinical presentation, diagnostic methods, and histopathologic findings in 27 cases of endometrial cancer in polyps. METHODS: A descriptive, retrospective study of 204 consecutive patients with endometrial carcinoma who were diagnosed at our institution between June 1998 to June 2001. Endometrial cancer arising in polyps occurred in 27 patients (13.2%) and accounted for 1.8% of 1492 endometrial polyps diagnosed during this period. RESULTS: Patients had a mean age of 62 years. All except one woman were postmenopausal. Three breast cancer patients were currently given tamoxifen. Metrorrhagia was the presenting symptom in 74% of cases, although 22% of patients were asymptomatic at the time of diagnosis. Ultrasonography performed in 22 patients showed images compatible with an endometrial polyp in 50% of cases, myoma in 5%, and inconclusive findings in 45%. The median endometrial thickness was 11 mm (range 4-33 mm). Diagnosis was made by aspiration-biopsy in 13 patients and by hysteroscopic endometrial sampling in 13 (in one patient endometrial carcinoma was incidentally found in the surgical specimen). All patients were in FIGO Stage IA. Endometrioid carcinoma was found in 81.5% of cases. Retroperitoneal metastases were not found in 25 patients undergoing pelvic lymphadenectomy, nor neoplastic growth in the specimens of six polypeptomies performed during hysteroscopy. All patients are free of relapse after a mean follow-up of 30 months. CONCLUSIONS: Postmenopausal women with endometrial polyps diagnosed by ultrasonography should undergo directed biopsies under hysteroscopic vision. The present series confirms the good prognosis of endometrial cancer in polyps.

[The comparative treatment with lovastatin and bezafibrate of primary hypercholesterolemia. A randomized and double-blind trial]. / Tratamiento comparativo de la hipercolesterolemia primaria con lovostatina y bezafibrato. Ensayo randomizado y a doble ciego.

The efficacy and tolerability of lovostatin (L) and bezafibrate (B) were compared in a total of 39 patients, 24 males and 15 females, 59 +/- 9 years old. Showing a total serum cholesterol superior to 250 mg/dl and total serum triglycerides inferior to 350 mg/dl, after 1 month on a low cholesterol diet and another on placebo, were eligible for participation. After randomization 19 treated with L started with 20 or 40 mg at night according to baseline cholesterol under or above 300 respectively and 20 with B received 200 mg tid. If after 6 weeks of therapy cholesterol remained above 200, the doses of L or matching placebo in those with B was double while dose of B or matching placebo remained constant. Cholesterol, triglycerides, LDL-cholesterol and HDL-cholesterol were determined using an enzymatic analytical method. Apolipoproteins were obtained by radial immunodiffusion. Routine hematological analysis and blood chemistry safety tests were performed at baseline and every 6 weeks during active treatment. The average most important results, after 12 weeks of treatment, comparing L vs B were: 1) cholesterol was reduced 26 vs 10% (p less than 0.001); 2) LDL-cholesterol decreased 35 vs 15% (p less than 0.001); 3) HDL-cholesterol increased 5 vs 19% (p = NS); 4) triglycerides diminished 15 vs 18% (p = NS). Three patients in L and 1 in B showed adverse events and two of them, one each group, were drop-out. In summary: a) L was more effective lowering total cholesterol and LDL-cholesterol; b) B was more potent decreasing triglycerides and increasing HDL-cholesterol; c) both drugs showed good tolerability.

[Necrosis of the greater curvature following acute dilatation of the stomach]. / Necrosis de curvadura mayor secuente a dilatación aguda de estómago.

We present a case of gastric greater curvature necrosis after acute gastric dilatation. The lesion was treated by vertical resection of the greater curvature and the distal end of the gastric fundus. This is the first case described in the Spanish medical literature.

p53 regulates the transcription of its Delta133p53 isoform through specific response elements contained within the TP53 P2 internal promoter.

The tumor suppressor p53 protein is activated by genotoxic stress and regulates genes involved in senescence, apoptosis and cell-cycle arrest. Nine p53 isoforms have been described that may modulate suppressive functions of the canonical p53 protein. Among them, Delta133p53 lacks the 132 proximal residues and has been shown to modulate p53-induced apoptosis and cell-cycle arrest. Delta133p53 is expressed from a specific mRNA, p53I4, driven by an alternative promoter P2 located between intron 1 and exon 5 of TP53 gene. Here, we report that the P2 promoter is regulated in a p53-dependent manner. Delta133p53 expression is increased in response to DNA damage by doxorubicin in p53 wild-type cell lines, but not in p53-mutated cells. Chromatin immunoprecipitation and luciferase assays using P2 promoter deletion constructs indicate that p53 binds functional response elements located within the P2 promoter. We also show that Delta133p53 does not bind specifically to p53 consensus DNA sequence in vitro, but competes with wild-type p53 in specific DNA-binding assays. Finally, we report that Delta133p53 counteracts p53-dependent growth suppression in clonogenic assays. These observations indicate that Delta133p53 is a novel target of p53 that may participate in a negative feedback loop controlling p53 function.

Estudio de caso. Terapia del movimiento inducido por restricción en parálisis cerebral infantil / Case report. Constraint-induced movement therapy in childhood cerebral palsy

Introducción. El caso trata de una niña de 30 meses de edad diagnosticada de parálisis cerebral con hemiparesia espástica. La intervención desde atención temprana se fundamenta en la aplicación de un protocolo modificado de terapia del movimiento inducido en entornos naturales (hogar y colegio). Objetivos. El objetivo es mejorar el desempeño ocupacional e incrementar el uso voluntario de la mano parética en actividades bimanuales, basándose en la estimulación neurológica implícita en el aprendizaje motor. Resultados. Mejora del desempeño en actividades de la vida diaria. Se registraron ganancias a nivel emocional y actitudinal. AHA incrementa 7 puntos. PDMS-2 suma 2 puntos en visual motora y 2 puntos en edad equivalente. A nivel funcional se alcanzan ganancias en 8 de los 10 objetivos (Goal Attainment Scale). Los resultados obtenidos invitan a seguir investigando el potencial de esta herramienta en entornos naturales (AU)

Introduction. We report the case of a 30-month-old girl with unilateral spastic cerebral palsy (CP). Early Intervention was based on an eco-modified protocol of constraint-induced movement therapy (mCIMT). Objectives. The objectives were to improve occupational development and to increase spontaneous upper limb use during bimanual activities by means of neurological stimulation involved in the leaning of motor skills. Results. There was improvement in the development of activities of daily living, as well as emotional and attitudinal gains. An increment of 7 points was recorded in the assisting hand assessment (AHA). The Peabody developmental motor sclaes-2 (PDMS-2) increased 2 points in the visual motor (VM) subtest and another 2 points in equivalent age (EA). In functional goals, progress was achieved in 8 of the 10 objectives (Goal Attainment Scale). The results obtained encourage us to keep investigating the potential of this tool in natural environments (AU)

El timerosal en la práctica pediátrica / Assisted reproductive techniques and child health

El mercurio no tiene ninguna función fisiológica en el cuerpo humano y está ampliamente distribuido en la naturaleza. Puede ser tóxico por inhalación, ingestión o contacto. El timerosal es una sal orgánica de mercurio usada como antiséptico y antifúngico desde 1928. Desde finales de la década de 1990, el mercurio empezó a ser retirado de los medicamentos y materiales de uso clínico. Se ha hecho un esfuerzo para eliminar el timerosal de las vacunas siguiendo el principio de precaución, pues no hay evidencias científicas que avalen un daño cerebral atribuible al timerosal. No se ha encontrado ninguna asociación entre su uso y el riesgo de desarrollar autismo. Actualmente, en los países de nuestro entorno solo se usa en muy pocas vacunas en envases multidosis, y todas las incluidas en los calendarios oficiales españoles, así como las de uso común en niños fuera de ellos (neumocócicas y rotavirus), están libres de timerosal. No obstante, la OMS ha reiterado que las vacunas que contienen timerosal pueden seguir utilizándose, especialmente en el Tercer Mundo donde, por necesidades logísticas, se utilizan envases multidosis, pues el riesgo ­real de enfermedad y muerte por enfermedades vacunables en quienes no se vacunan es muy superior al riesgo hipotético derivado del su uso. Como con cualquier otro medicamento, pueden presentarse reacciones de hipersensibilidad al timerosal, generalmente locales. Los esfuerzos investigadores sobre determinados problemas neurológicos como el autismo deberían encaminarse a buscar sus verdaderas causas en lugar de a sembrar dudas sobre la seguridad de las vacunas (AU)

Mercury has no physiological function in the human body and is widely distributed in nature. It may be toxic by inhalation, ingestion or contact. Thimerosal is an organic salt of mercury used as an antiseptic and antifungal since 1928. Since the late 1990s, mercury began to be withdrawn from drugs and materials for clinical use. An effort has been made to remove thimerosal from vaccines as a precautionary principle, since there is no scientific evidence to substantiate that brain damage can be attributable to thimerosal. No connection has been found between its use and the risk of developing autism. In the Western World it is only currently used in very few vaccines in multidose containers, whereas all those included in Spanish Schedules, as well as in those commonly used for children outside them (pneumococcal and rotavirus), are free from thimerosal. However, the WHO has reiterated that vaccines containing thimerosal may still be used, especially in the Third World where, for logistical needs, multidose containers are used, as the real risk of illness and death by vaccianble diseases in those who do not get vaccinated is much higher than the hypothetical risk arising from their use. As with any medicine, there may be hypersensitivity reactions to thimerosal, usually local. Research efforts should be directed towards finding the real causes of neurological problems like autism instead of throwing doubts about the safety of vaccines (AU)

Eating attitudes, sociodemographic factors and body shape evaluation in adolescence.

The Eating Attitudes Test (EAT) and another questionnaire aimed at sociodemographic and body shape information were administered to an adolescent population of 1554 students from Barcelona in the 12-19 age group. The highest scores on EAT were obtained by girls, older adolescents, overweight adolescents, adolescents practising restrictive diets, adolescents considering themselves obese and those wishing to modify their body size. The same characteristics were associated with EAT scores higher than 30 (the cut-off score, established by the authors of the questionnaire, above which the anorexic population is placed). Results are analysed in terms of sociocultural pressures on adolescents, particularly females, who are subjected to the 'culture of slenderness'.