Effects of locally applied Insulin-like Growth Factor-I on osseointegration.

BACKGROUND: The aim of this study was to assess the effect of local application of IGF-I on osseointegration of dental implants placed in osteoporotic bones. MATERIAL AND METHODS: 16 rabbits were randomly distributed into two groups: eight animals were ovariectomized and fed a low-calcium diet for six weeks, in order to induce experimental osteoporosis, and the others were sham-operated and fed a standard diet. A titanium implant was inserted into the tibiae in both groups. In half of the rabbits, 4 µg of IGF-I was applied into the ostectomy, prior to the implant insertion. A total of 32 implants were placed. Animals were sacrificed two weeks after surgery and decalcified samples were processed for Bone-To-Implant Contact (BIC) and Bone Area Density (BAD) measurements. Analysis of variance (ANOVA) was used for statistical evaluation. P<0.05 was considered to be significant. RESULTS: Ovariectomy induced statistically significant lower BAD values (p=0.008) and a tendency towards lower BIC values when compared osteoporotic and healthy groups. The administration of 4 µg of IGF-I did not produce statistically significant differences neither on BIC nor on BAD values, neither in the osteoporotic animals nor in healthy. CONCLUSIONS: Within the limitations of this experimental study, local administration of 4 µg of IGF-I was not able to induce any changes in the osseointegration process two weeks after surgery, neither in healthy rabbits nor in the osteoporotic group.

Guidelines for the diagnosis and treatment of cutaneous squamous cell carcinoma: a GRADE approach for evidence evaluation and recommendations by the Italian Association of Medical Oncology.

Cutaneous squamous cell carcinoma (CSCC) accounts for ∼20%-25% of all skin tumors. Its precise incidence is often challenging to determine due to limited statistics and its incorporation with mucosal forms. While most cases have a favorable prognosis, challenges arise in patients presenting with locally advanced or metastatic forms, mainly appearing in immunocompromised patients, solid organ transplantation recipients, or those facing social difficulties. Traditionally, chemotherapy and targeted therapy were the mainstays for advanced cases, but recent approvals of immunotherapeutic agents like cemiplimab and pembrolizumab have revolutionized treatment options. These guidelines, developed by the Italian Association of Medical Oncologists (AIOM) using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach, aim to guide clinicians in diagnosing, treating, and monitoring patients with CSCC, covering key aspects from primitive tumors to advanced stages, selected by a panel of experts selected by AIOM and other national scientific societies. The incorporation of these guidelines into clinical practice is expected to enhance patient care and address the evolving landscape of CSCC management.

Advances in surface design and biomedical applications of magnetic nanoparticles.

Despite significant efforts by scientists in the development of advanced nanotechnology materials for smart diagnosis devices and drug delivery systems, the success of clinical trials remains largely elusive. In order to address this biomedical challenge, magnetic nanoparticles (MNPs) have gained attention as a promising candidate due to their theranostic properties, which allow the simultaneous treatment and diagnosis of a disease. Moreover, MNPs have advantageous characteristics such as a larger surface area, high surface-to-volume ratio, enhanced mobility, mass transference and, more notably, easy manipulation under external magnetic fields. Besides, certain magnetic particle types based on the magnetite (Fe3O4) phase have already been FDA-approved, demonstrating biocompatible and low toxicity. Typically, surface modification and/or functional group conjugation are required to prevent oxidation and particle aggregation. A wide range of inorganic and organic molecules have been utilized to coat the surface of MNPs, including surfactants, antibodies, synthetic and natural polymers, silica, metals, and various other substances. Furthermore, various strategies have been developed for the synthesis and surface functionalization of MNPs to enhance their colloidal stability, biocompatibility, good response to an external magnetic field, etc. Both uncoated MNPs and those coated with inorganic and organic compounds exhibit versatility, making them suitable for a range of applications such as drug delivery systems (DDS), magnetic hyperthermia, fluorescent biological labels, biodetection and magnetic resonance imaging (MRI). Thus, this review provides an update of recently published MNPs works, providing a current discussion regarding their strategies of synthesis and surface modifications, biomedical applications, and perspectives.

Guidelines for the diagnosis and treatment of basal cell carcinoma: a GRADE approach for evidence evaluation and recommendations by the Italian Association of Medical Oncology.

Basal cell carcinoma (BCC) is the most common form of cancer, with a high impact on the public health burden and social costs. Despite the overall prognosis for patients with BCC being excellent, if lesions are allowed to progress, or in a small subset of cases harboring an intrinsically aggressive biological behavior, it can result in local spread and significant morbidity, and conventional treatments (surgery and radiotherapy) may be challenging. When a BCC is not amenable to either surgery or radiotherapy with a reasonable curative intent, or when metastatic spread occurs, systemic treatments with Hedgehog inhibitors are available. These guidelines were developed, applying the GRADE approach, on behalf of the Italian Association of Medical Oncologists (AIOM) to assist clinicians in treating patients with BCC. They contain recommendations with regard to the diagnosis, treatment and follow-up, from primitive tumors to those locally advanced or metastatic, addressing the aspects of BCC management considered as priorities by a panel of experts selected by AIOM and other national scientific societies. The use of these guidelines in everyday clinical practice should improve patient care.

Focal adhesion kinase governs cardiac concentric hypertrophic growth by activating the AKT and mTOR pathways.

The heart responds to sustained overload by hypertrophic growth in which the myocytes distinctly thicken or elongate on increases in systolic or diastolic stress. Though potentially adaptive, hypertrophy itself may predispose to cardiac dysfunction in pathological settings. The mechanisms underlying the diverse morphology and outcomes of hypertrophy are uncertain. Here we used a focal adhesion kinase (FAK) cardiac-specific transgenic mice model (FAK-Tg) to explore the function of this non-receptor tyrosine kinase on the regulation of myocyte growth. FAK-Tg mice displayed a phenocopy of concentric cardiac hypertrophy, reflecting the relative thickening of the individual myocytes. Moreover, FAK-Tg mice showed structural, functional and molecular features of a compensated hypertrophic growth, and preserved responses to chronic pressure overload. Mechanistically, FAK overexpression resulted in enhanced myocardial FAK activity, which was proven by treatment with a selective FAK inhibitor to be required for the cardiac hypertrophy in this model. Our results indicate that upregulation of FAK does not affect the activity of Src/ERK1/2 pathway, but stimulated signaling by a cascade that encompasses PI3K, AKT, mTOR, S6K and rpS6. Moreover, inhibition of the mTOR complex by rapamycin extinguished the cardiac hypertrophy of the transgenic FAK mice. These findings uncover a unique role for FAK in regulating the signaling mechanisms that governs the selective myocyte growth in width, likely controlling the activity of PI3K/AKT/mTOR pathway, and suggest that FAK activation could be important for the adaptive response to increases in cardiac afterload. This article is part of a Special Issue entitled "Local Signaling in Myocytes".

Form follows function: morphological diversification and alternative trapping strategies in carnivorous Nepenthes pitcher plants.

Carnivorous plants of the genus Nepenthes have evolved a striking diversity of pitcher traps that rely on specialized slippery surfaces for prey capture. With a comparative study of trap morphology, we show that Nepenthes pitcher plants have evolved specific adaptations for the use of either one of two distinct trapping mechanisms: slippery wax crystals on the inner pitcher wall and 'insect aquaplaning' on the wet upper rim (peristome). Species without wax crystals had wider peristomes with a longer inward slope. Ancestral state reconstructions identified wax crystal layers and narrow, symmetrical peristomes as ancestral, indicating that wax crystals have been reduced or lost multiple times independently. Our results complement recent reports of nutrient source specializations in Nepenthes and suggest that these specializations may have driven speciation and rapid diversification in this genus.

An in silico analysis of Ibuprofen enantiomers in high concentrations of sodium chloride with SARS-CoV-2 main protease.

2020 will be remembered worldwide for the outbreak of Coronavirus disease (COVID-19), which quickly spread until it was declared as a global pandemic. The main protease (Mpro) of SARS-CoV-2, a key enzyme in coronavirus, represents an attractive pharmacological target for inhibition of SARS-CoV-2 replication. Here, we evaluated whether the anti-inflammatory drug Ibuprofen, may act as a potential SARS-CoV-2 Mpro inhibitor, using an in silico study. From molecular dynamics (MD) simulations, we also evaluated the influence of ionic strength on the affinity and stability of the Ibuprofen-Mpro complexes. The docking analysis shows that R(-)Ibuprofen and S(+)Ibuprofen isomers can interact with multiple key residues of the main protease, through hydrophobic interactions and hydrogen bonds, with favourable binding energies (-6.2 and -5.7 kcal/mol, respectively). MM-GBSA and MM-PBSA calculations confirm the affinity of these complexes, in terms of binding energies. It also demonstrates that the ionic strength modifies significantly their binding affinities. Different structural parameters calculated from the MD simulations (120 ns) reveal that these complexes are conformational stable in the different conditions analysed. In this context, the results suggest that the condition 2 (0.25 NaCl) bind more tightly the Ibuprofen to Mpro than the others conditions. From the frustration analysis, we could characterize two important regions (Cys44-Pro52 and Linker loop) of this protein involved in the interaction with Ibuprofen. In conclusion, our findings allow us to propose that racemic mixtures of the Ibuprofen enantiomers might be a potential treatment option against SARS-CoV-2 Mpro. However, further research is necessary to determinate their possible medicinal use.Communicated by Ramaswamy H. Sarma.

Atypical esophageal vascular lesions observed in liver cirrhosis.

Chronic liver disease is known to be associated with several vascular alterations including portal hypertension and hepato-pulmonary insufficiency. We report a case of esophageal vascular lesions resembling spider naevi in a patient with nonalcoholic cirrhosis who underwent an upper gastrointestinal (GI) endoscopy. We observed the presence of multiple white round elevations, 5-6 mm in size, with radiating thin-walled vessels, in the middle and distal esophagus. The histological examination documented the presence of multiple dilated blood vessels in the mucosal layer of the esophagus, with striking thickening of the endothelium wall. There was no evidence of esophagogastric varices, but only of a moderate congestive antral gastropathy. To our knowledge, these endoscopic esophageal findings have not yet been described in cirrhosis.

Protection of ovarian tissue from radiotherapy.

Advances researches in the diagnosis and treatment of childhood, adolescent and adult cancer have greatly increased the life expectancy of premenopausal women with cancer. However, one of the serious side effects of these treatments is the risk of damage to fertility. The ovaries are very sensitive to cytotoxic and radiotherapeutic treatment. The only established method of fertility preservation is embryo cryopreservation according to the Ethics Committee of the American Society for Reproductive Medicine (2005), but this option requires the patient to be of pubertal age, have a partner or use donor sperm, and be able to undergo a cycle of ovarian stimulation, which is not possible when the radiotherapy has to be initiated immediately or when stimulation is contraindicated according to the type of cancer. For patients who need immediate radiotherapy, cryopreservation of ovarian tissue is the only possible alternative. This manuscript reports the different techniques of cryopreservation and the results of transplantation of cryopreserved ovarian tissue. The current techniques allow cryopreservation of human ovarian fragments for a long time with good follicular survival rate after thawing. Numerous studies ultimately in this field have demonstrated to improve the survival rate of the oocytes and cryopreserved follicles. Moreover this manuscript includes a case of a 17-year-old girl who had to undergo pelvic irradiation for non-Hodgkin's lymphoma and the laparoscopic treatment to preserve the fertility (Fig. 2, Ref. 47).

Effects of long-term administration of Lactobacillus reuteri DSM-17938 on circulating levels of 5-HT and BDNF in adults with functional constipation.

Accumulated evidence shows that some probiotic strains ameliorate functional constipation (FC) via the modulation of specific gastrointestinal peptide pathways. The aims of this study were to investigate: (1) the effects of long-term administration of Lactobacillus reuteri (LR) DSM 17938 on the serum levels of serotonin (5-HT) and brain-derived neurotrophic factor (BDNF); (2) the possible link between 5-HT, BDNF, and specific constipation-related symptoms; (3) whether genetic variability at the 5-HTT gene-linked polymorphic region (5-HTTLPR) and BDNF Val66Met loci could be associated with serum 5-HT and BDNF variations. LR DSM 17938 was administered to 56 FC patients for 105 days in a randomised, double-blind manner. The fasting blood samples were collected during the randomisation visit (V1), at day 15 (induction period, V2), day 60 (intermediate evaluation, V3), and day 105 (V4) and the Constipaq questionnaire (the sum of Constipation Scoring System (CSS) and patient assessment constipation quality of life (PAC-QoL)) was administered. A group of healthy subjects was enrolled as controls (HC). At V1, the mean serum 5-HT level in the whole patient group was significantly higher (P=0.027) than in HC subjects, while serum BDNF did not. At the end of probiotic administration (V4), 5-HT and BDNF levels were significantly lower than the initial values (V1) (P=0.008 and P=0.015, respectively). 5-HT and BDNF serum concentration were significantly associated (r=0.355; P=0.007). Neither 5-HT nor BDNF serum levels correlated with the CSS item scores and with the PAC-QoL. Lastly, the regression analysis demonstrated that the presence of the S allele of the 5-HTTLPR accounted for the reduction in the 5-HT concentration at V4. In conclusion, the long-term administration of LR DSM 17938 demonstrated that such a probiotic strain could improve FC by affecting 5-HT and BDNF serum concentrations.

Effect of maternal heat-stress on follicular growth and oocyte competence in Bos indicus cattle.

The objective was to determine whether exposure of Gir (Bos indicus) cows to heat-stress (HS) causes immediate and delayed deleterious effect on follicular dynamics, hormonal profile and oocyte competence. The cows were kept in tie-stalls for an adaptive thermoneutral period of 28 days (Phase I, Days -28 to -1). In Phase II (Days 0-28) cows were randomly allocated into control (CG, n=5) and HS (HS, n=5) treatments. The HS cows were placed in an environmental chamber at 38 degrees C and 80% relative humidity (RH) during the day and 30 degrees C, 80% RH during the night for 28 days. The CG group was maintained in shaded tie-stalls (ambient temperature) for 28 days. During Phase III (Days 28-147) animals were placed in tie-stalls (Days 28-42) followed by pasture (Days 42-147) under thermoneutrality. In each phase, weekly ovum pick up (OPU) sessions were to evaluate follicular development, morphology of cumulus-oocyte complexes (COCs), and developmental competence after in vitro maturation, fertilization, and culture. Serum concentrations of progesterone (P(4)) and cortisol were evaluated by radioimmunoassay. Exposure of Gir cows to HS had no immediate effect on reproductive function, but exerted a delayed deleterious effect on ovarian follicular growth, hormone concentrations, and oocyte competence. Heat-stress increased the diameter of the first and second largest follicles from Days 28 to 49. Indeed, HS increased the number of >9 mm follicles (characterized as follicular codominance) during this phase. Cows exposed to HS had longer periods of non-cyclic activity (P(4)<1 ng/mL), as well as shorter estrous cycles. However, HS did not affect cortisol concentration as compared to CG. Although HS had no significant effect on cleavage rate, it reduced blastocyst development during Phase III. In conclusion, long-term exposure of B. indicus cattle to HS had a delayed deleterious effect on ovarian follicular dynamics and oocyte competence.

The influence of speed and size on avian terrestrial locomotor biomechanics: Predicting locomotion in extinct theropod dinosaurs.

How extinct, non-avian theropod dinosaurs moved is a subject of considerable interest and controversy. A better understanding of non-avian theropod locomotion can be achieved by better understanding terrestrial locomotor biomechanics in their modern descendants, birds. Despite much research on the subject, avian terrestrial locomotion remains little explored in regards to how kinematic and kinetic factors vary together with speed and body size. Here, terrestrial locomotion was investigated in twelve species of ground-dwelling bird, spanning a 1,780-fold range in body mass, across almost their entire speed range. Particular attention was devoted to the ground reaction force (GRF), the force that the feet exert upon the ground. Comparable data for the only other extant obligate, striding biped, humans, were also collected and studied. In birds, all kinematic and kinetic parameters examined changed continuously with increasing speed, while in humans all but one of those same parameters changed abruptly at the walk-run transition. This result supports previous studies that show birds to have a highly continuous locomotor repertoire compared to humans, where discrete 'walking' and 'running' gaits are not easily distinguished based on kinematic patterns alone. The influences of speed and body size on kinematic and kinetic factors in birds are developed into a set of predictive relationships that may be applied to extinct, non-avian theropods. The resulting predictive model is able to explain 79-93% of the observed variation in kinematics and 69-83% of the observed variation in GRFs, and also performs well in extrapolation tests. However, this study also found that the location of the whole-body centre of mass may exert an important influence on the nature of the GRF, and hence some caution is warranted, in lieu of further investigation.

Melanocytic nevi and non-neoplastic hyperpigmentations.

This is the first of three chapters that will be progressively published on Pathologica as updating activity of the Italian Study Group of Dermatopathology (GISD), Italian Society of Pathology and Cytology (SIAPeC IAP). The first chapter concerns non-neoplastic hyperpigmented skin lesions and nevi, the second will address the topics of dysplastic nevus, borderline and low malignant potential melanocytic proliferations and the third melanoma in its variants and differential diagnoses with a supplement on the immunohistochemistry and molecular support to diagnostic and prognostic definition of nevi and melanomas. Although we believe that great advances were made in the application of ancillary genetic, immunohistochemical and molecular techniques, for the diagnosis and biological characterization of melanocytic tumors the morphology still remains the gold standard. These chapters are not intended as substitutes or even claim to be compared to the numerous and valuable texts that are also recently published, but they want to present, concisely and quickly available, all of those traits that we believe essential to the histopathological evaluation of a melanocytic lesion. No morphological parameter is exclusive and individually sufficient to make the correct diagnosis of nevus or melanoma but to reach a final conclusive and appropriate interpretation a set of morphological characters must be evaluated and compared. I was lucky enough to be able to examine several thousand cases and to draw lessons from each of these increasing my diagnostic experience. I had a great lesson by my teacher and good friend Prof. Martin C. Mihm Jr of Boston, dermato-pathologist with undisputed international reputation, who, with great passion, patience and friendship, transferred me much of his experience and knowledge and for which I always thank him. Special thanks I would like to address Dr. Agostino Crupi, dermatologist, skin-oncologist and brilliant dermatoscopist who taught me how the diagnosis of melanocytic lesions starts from the clinic examination and the mutual comparison between dermatologist and pathologist is a great richness of knowledge for both. Finally thank to my collaborators Barbara Rubino, Barbara Bruni and Antonella Festa for the large number of material collected in these years at the Pathology Service of the IRCCS Policlinico San Donato and a particular thank to Marco Turina who collaborated in the drafting of this text.

Efectividad de la punción seca en el compartimento medial de la rodilla en paciente con osteoartritis. Caso clínico / Effectiveness of dry needling in the medial compartment of the knee in patient with osteoarthritis. Clinical case

Objetivo: Determinar la efectividad del tratamiento con punción seca para eliminar el síndrome de dolor miofascial en una paciente con gonartrosis y puntos gatillo no miofasciales activos en el compartimento medial de la rodilla. Material y métodos: Mujer de 69 años con osteoartritis generalizada e importante deformidad en genu varum de ambas rodillas. Se valora mediante palpación la presencia de puntos dolorosos en el compartimento medial de la rodilla más limitada, y son tratados con punción seca mediante la técnica de inserciones múltiples rápidas de Hong. Resultados: Se realiza un seguimiento de 4 semanas de tratamiento mientras se registran los datos relacionados con la percepción del dolor al inicio de la técnica, durante la misma y tras ella, y se objetiva la evolución del umbral de dolor a la presión en los puntos más dolorosos del compartimento medial de cada visita. Al finalizar el estudio, se demuestra la eficacia analgésica tras el análisis del registro. Conclusiones: La técnica de inserciones múltiples rápidas de Hong sobre los puntos gatillo no miofasciales de una rodilla con degeneración medial provocada por osteoartritis es eficaz en el tratamiento del dolor y, por tanto, en el aumento de la calidad de vida de la paciente, debiendo considerarse como una opción de tratamiento válida a la hora de abordar su cuadro clínico.(AU)

Objective: To determine the effectiveness of treatment with dry needling to eliminate myofascial pain syndrome in a patient with gonarthrosis and active non-myofascial trigger points in the medial compartment of her knee. Material and methods: A 69-year-old woman with generalized osteoarthritis and significant genu varum deformity of both knees. In the medial knee compartment, the tender points of the more limited knee were palpated and treated with dry needling using Hong's rapid multiple insertion technique. Results: A 4-week follow-up of treatment was carried out, and the data relating to the perception of pain were recorded at the beginning of the technique, during and after it, along with the evolution of the pressure pain threshold in the most painful points in the medial compartment during each visit. At the end of the study, analgesic efficacy was proven, after analysis of the records. Conclusions: Hong's rapid multiple needle insertion technique in the non-myofascial trigger points of the knee with medial degeneration caused by osteoarthritis was effective in the treatment of pain and, therefore, improved the quality of life of the patient, so it should be considered a valid treatment option in her rheumatological disease.(AU)

New sepsis criteria: do they replace or complement what is known in the approach to the infectious patient?

There have recently been profound changes in both the definitions of sepsis and septic shock and the diagnostic criteria established for daily clinical practice. In addition, a new screening tool known as qSOFA has been introduced to identify patients at risk of a poor short-term outcome. This score has been accompanied by some controversy due to presenting a lower sensitivity than the systemic inflammatory response criteria previously used to identify such patients. In this article, we shall summarise and analyse the most important recently published studies in relation to these new criteria.

Control de calidad en nutrición parenteral neonatal, empleando como método validado el análisis bioquímico / Quality control in neonatal parenteral nutrition, using biochemical analysis as a validated method

Objetivos: El objetivo de este estudio es describir el método empleado como control de calidad en las nutriciones parenterales de neonatos en un hospital de tercer nivel, así como realizar un análisis estadístico de los resultados del mismo.Material y métodos: En nuestro centro se realiza un análisis bioquímico de los niveles de glucosa, potasio y calcio de todas las nutriciones parenterales neonatales como método de control de calidad. Dicho análisis se realiza mediante técnicas previamente validadas. Se evaluaron todas las nutriciones parenterales neonatales elaboradas durante el periodo comprendido entre julio de 2018 y noviembre de 2019. Todas las mezclas analizadas contenían lípidos. Para el análisis estadístico de los resultados se consideró un ±10% sobre la concentración teórica como margen de aceptación.Resultados: Se analizaron 950 mezclas y se obtuvieron las rectas de regresión lineal para establecer la correlación entre el valor teórico y real de los componentes analizados.Conclusiones: Destaca la importancia que tiene el establecimiento de un control de calidad de las nutriciones parenterales neonatales, para la detección y prevención de errores durante la preparación de las mismas y previamente a su dispensación. (AU)

Objectives: We aimed to describe the method used as neonatal parenteral nutrition quality control in a third level hospital, as well as to carry on a statistical analysis of its results.Methods: In our center, a biochemical analysis of glucose, potassium and calcium levels of all neonatal parenteral nutrition is performed as a quality control method. This analysis is carried out using previously validated techniques. All neonatal parenteral nutrition prepared during the period between July 2018 and November 2019 were evaluated. All the mixtures analyzed contained lipids. For the statistical analysis of the results, ±10% of the theoretical concentration was considered as the acceptance margin.Results: 950 mixtures were analyzed and linear regression lines were obtained to establish the correlation between the theoretical and real value of the analyzed components.Conclusions: In conclusion, the importance of establishing quality control of neonatal parenteral nutrition is highlighted, for the detection and prevention of errors during their preparation and prior to their dispensing. (AU)

[International adoption of children from Ethiopia and language: a pilot study]. / Adopcion internacional de niños de Etiopia y lenguaje: un estudio piloto.

INTRODUCTION: Children who have gone through international adoption offer a great and unique learning opportunity around language development. Time elapsed since the first international adoptions took place in Spain has given a unique opportunity to research and conclude whether learning the second language follows the same developmental patterns and outcomes as compared to acquiring tongue language. AIM: To verify whether the evaluated subjects have reached the expected use and language proficiency for their chronological age. SUBJECTS AND METHODS: This pilot study focuses on the evaluation of language acquired in the first years of adolescence of 7 Ethiopian children who have lived over 8 years in Spain. CELF-4 test and the verbal tests of the WISC-IV have been administered. Scores have been analyzed and compared to the control group (same age group). In order to generate qualitative information about parents' concerns an on-line questionnaire has been administered in a form of a semi-structured interview. RESULTS: Both the CELF-4 test and the WISC-IV verbal tests reflect average or low average results in language abilities. Qualitative interviews reflect deep concern about academic outcome. CONCLUSIONS: Subjects in this study are showing an average to low average proficiency in the Spanish language. The results, nevertheless, do not explain the academic difficulties shown.

TITLE: Adopcion internacional de niños de Etiopia y lenguaje: un estudio piloto.Introduccion. Los niños que han vivido una adopcion internacional ofrecen una oportunidad unica de conocer como ocurre el desarrollo del lenguaje. El tiempo que ha transcurrido desde que en nuestro pais se iniciaran las primeras adopciones internacionales esta permitiendo investigar si el desarrollo inicial del lenguaje culmina en una equiparacion real. Objetivo. Comprobar si se ha producido en los sujetos evaluados una equiparacion real en el lenguaje de acuerdo con lo esperado con su edad cronologica. Sujetos y metodos. En este estudio piloto se realiza una valoracion del lenguaje adquirido en los primeros años de la adolescencia de siete niños etiopes que han vivido ya mas de ocho años en España. Para ello se analizan las puntuaciones obtenidas por los siete sujetos en la prueba CELF-4 y en las puntuaciones de las pruebas verbales del WISC-IV, teniendo como referencia a su grupo normativo de edad (grupo control). Para obtener informacion cualitativa sobre las preocupaciones de los padres se ha administrado un cuestionario online a traves de una entrevista semiestructurada. Resultados. Tanto el CELF-4 como las pruebas verbales del WISC-IV estan reflejando un funcionamiento promedio o promedio-bajo en las competencias verbales analizadas. Las entrevistas cualitativas reflejan elevados niveles de preocupacion acerca del rendimiento academico. Conclusiones. Los sujetos del estudio parecen mostrar un funcionamiento promedio o promedio bajo en el uso del castellano. Las puntuaciones obtenidas, sin embargo, no parecen poder explicar las dificultades que estan manifestando en el ambito escolar.

Using step width to compare locomotor biomechanics between extinct, non-avian theropod dinosaurs and modern obligate bipeds.

How extinct, non-avian theropod dinosaurs locomoted is a subject of considerable interest, as is the manner in which it evolved on the line leading to birds. Fossil footprints provide the most direct evidence for answering these questions. In this study, step width-the mediolateral (transverse) distance between successive footfalls-was investigated with respect to speed (stride length) in non-avian theropod trackways of Late Triassic age. Comparable kinematic data were also collected for humans and 11 species of ground-dwelling birds. Permutation tests of the slope on a plot of step width against stride length showed that step width decreased continuously with increasing speed in the extinct theropods (p < 0.001), as well as the five tallest bird species studied (p < 0.01). Humans, by contrast, showed an abrupt decrease in step width at the walk-run transition. In the modern bipeds, these patterns reflect the use of either a discontinuous locomotor repertoire, characterized by distinct gaits (humans), or a continuous locomotor repertoire, where walking smoothly transitions into running (birds). The non-avian theropods are consequently inferred to have had a continuous locomotor repertoire, possibly including grounded running. Thus, features that characterize avian terrestrial locomotion had begun to evolve early in theropod history.

Overexpression of the T-cell receptor beta-chain variable region TCRBV14 in HLA-A2-matched primary human melanomas.

We have shown previously that peripheral blood lymphocytes (PBL) of patients with metastatic melanoma include cytotoxic T-cell clones that recognize Melan-A/MART-1 in a HLA-A2-restricted fashion. Such clones preferentially use the variable (V) regions TCRBV14 or TCRBV7 in the beta-chain of their T-cell receptor (TCRB). It was not known, however, whether this finding is associated with the presence of the HLA-A2 allele in tumor tissue and whether evidence of the predominance of these TCRBV families can also be observed in primary tumor tissue. To address these issues, we have used a semiquantitative PCR to examine the TCRBV repertoire in six HLA-A2-matched primary melanomas in comparison with their autologous PBL. Although each patient had his or her own pattern of skewed TCRBV utilization, in all patients, T-cells that used TCRBV14 were significantly overrepresented in the neoplastic site compared with PBL. All of the primary tumors studied had detectable expression of Melan-A/MART-1 and gp100, and immunohistochemical analysis confirmed the presence of the HLA-A2 allele. Additional samples of Melan-A/MART-1-positive, gp100-positive primary melanomas from six non-HLA-A2 patients and four autologous normal skin controls failed to reveal a TCRBV14 predominance in such tissues. These results point to a role of TCRBV14 T lymphocytes in the HLA-A2-restricted immune recognition of primary melanomas.

Effect of flutamide-induced androgen-receptor blockade on adenylate cyclase activation through G-protein coupled receptors in rat prostate.

The effect of the antiandrogen flutamide on the prostatic vasoactive intestinal peptide (VIP) receptor/effector system was studied in rats. Rats were s.c. injected with a daily dose of flutamide (15 mg/kg B.W.) or vehicle for 14 days. Drug treatment resulted in histological evidence of gland involution and increased plasma membrane fluidity as estimated by fluorescence spectroscopy. The number of VIP receptors and the stimulatory effect of VIP on adenylate cyclase activity in prostatic membranes decreased in flutamide-treated rats. However, the pattern of forskolin stimulation of the enzyme activity was not modified by this drug. Androgen-receptor blockade by flutamide also decreased the prostatic levels of alpha(s,) alpha(i1/2), and alpha(i3/0) G-protein subunits, as estimated by an immunological procedure. Whereas apoptotic DNA fragmentation was evidenced in prostate from 3-day castrated animals, a heterogeneous electrophoretic pattern was observed after flutamide treatment. Thus, androgen-receptor blockade by flutamide results in an important impairment of the components of the VIP receptor/effector system in rat prostate as well as in a modification of their coupling extent, which is presumably due to differences observed in plasma membrane fluidity. These results represent a crosstalk in the prostate between two mechanisms of signal transduction involved in cell proliferation.