[The importance of genetics in the study of hypertriglyceridemia]. / La importancia de la genética en el estudio de la hipertrigliceridemia.

Hypertriglyceridemia encompasses a set of lipid disorders common in clinical practice, generally defined as a fasting concentration above 150mg/dL. There are various classifications of the severity of hypertriglyceridaemia based on serum values, with levels generally considered moderate when below 500mg/dL and severe when above 1000mg/dL. Its importance lies in its association with other alterations in the lipid profile, contributing to increased cardiovascular risk and increased risk of acute pancreatitis, mainly with concentrations above 500mg/dL.

Adverse effects of sodium-glucose cotransporter-2 inhibitors in patients with heart failure: a systematic review and meta-analysis.

Sodium-glucose cotransoporter-2 inhibitors (SGLT-2Is) improve prognosis in heart failure (HF) patients both with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF). However, these drugs can have some side effects. To estimate the relative risk of side effects in HF patients treated with SGLT-2Is irrespective from left ventricular EF and setting (chronic and non-chronic HF). Five randomized controlled trials (RCTs) enrolling patients with HFrEF, 4 RCTs enrolling non-chronic HF, and 3 RCTs enrolling HFpEF were included. Among side effects, urinary infection, genital infection, acute kidney injury, diabetic ketoacidosis, hypoglycemia, hyperkalemia, hypokalemia, bone fractures, and amputations were considered in the analysis. Overall, 24,055 patients were included in the analysis: 9020 (38%) patients with HFrEF, 12,562 (52%) with HFpEF, and 2473 (10%) with non-chronic HF. There were no differences between SGLT-2Is and placebo in the risk to develop diabetic ketoacidosis, hypoglycemia, hyperkalemia, hypokalemia, bone fractures, and amputations. HFrEF patients treated with SGLT-2Is had a significant reduction of acute kidney injury (RR = 0.54 (95% CI 0.33-0.87), p = 0.011), whereas no differences have been reported in the HFpEF group (RR = 0.94 (95% CI 0.83-1.07), p = 0.348) and non-chronic HF setting (RR = 0.79 (95% CI 0.55-1.15), p = 0.214). A higher risk to develop genital infection (overall 2.57 (95% CI 1.82-3.63), p < 0.001) was found among patients treated with SGLT-2Is irrespective from EF (HFrEF: RR = 1.96 (95% CI 1.17-3.29), p = 0.011; HFpEF: RR = 3.04 (95% CI 1.88-4.90), p < 0.001). The risk to develop urinary infections was increased among SGLT-2I users in the overall population (RR = 1.13 (95% CI 1.00-1.28), p = 0.046) and in the HFpEF setting (RR = 1.19 (95% CI 1.02-1.38), p = 0.029), whereas no differences have been reported in HFrEF (RR = 1.05 (95% CI 0.81-1.36), p = 0.725) and in non-chronic HF setting (RR = 1.04 (95% CI 0.75-1.46), p = 0.806). SGLT-2Is increase the risk of urinary and genital infections in HF patients. In HFpEF patients, the treatment increases the risk of urinary infections compared to placebo, whereas SGLT-2Is reduce the risk of acute kidney disease in patients with HFrEF.

[Monogenic form of secondary arterial hypertension]. / Forma monogénica de hipertensión arterial secundaria.

Multiple diagnostic entities are included among the causes of secondary arterial hypertension, so an appropriate screening is essential to diagnose potentially treatable pathologies. Genetic syndromes occupy a small percentage of these causes. The latter group includes Liddle syndrome, a rare genetic disease with autosomal dominant inheritance, caused by gain-of-function mutations in the genes that code for the epithelial sodium channel (ENaC), involved in sodium reabsorption in the distal renal tubules. The presence of a family history of arterial hypertension with onset at an early age and hypokalemia in some of them should lead to the suspicion of this genetic disorder, which must be confirmed with genetic tests. We describe a case, genetically confirmed, in which hypertension refractory to conventional treatment is the only manifestation of said syndrome, making diagnosis difficult and delayed until adulthood.

[Posterior reversible encephalopathy syndrome (PRES) as a presentation of AL amyloidosis]. / Síndrome de encefalopatía posterior reversible (PRES) como forma de presentación de una amiloidosis AL.

Posterior reversible encephalopathy syndrome (PRES) is a clinical and radiological entity linked to multiple aetiologies with similar neuroimaging findings. Its incidence is unknown, and its pathogenesis is multifactorial, encompassing phenomena of endothelial dysfunction and cerebral flow autoregulation, inter alia. There is a wide variety of associated conditions, the most frequent being hypertension, eclampsia, and immunosuppressive therapy, along with other drugs, autoimmune diseases, and even uraemia. We present the case of a reversible posterior encephalopathy syndrome secondary to renal involvement as a debut form of AL amyloidosis.

Arterial hypertension of infrequent cause.

Arterial hypertension is generally classified as primary or essential (90%), and secondary (10%). Infrequent causes of the latter include Cushing's syndrome, classified as ACTH-dependent and independent. A small percentage of ACTH-independent cases are due to ectopic ACTH secretion, generally due to neoplasia, and can present as arterial hypertension and hyperglycaemia that are refractory to pharmacological measures, metabolic alkalosis and hypokalaemia that are difficult to control, but which help guide the initial diagnosis. We present two clinical cases with a diagnosis of ectopic ACTH secretion secondary to small cell lung carcinoma, in which one of the debut manifestations was unknown, difficult to control arterial hypertension.

Disease-free zones: bilateral recognition procedure in South America. / Zonas libres de enfermedades: proceso de reconocimiento bilateral en América del Sur.

According to the World Organisation for Animal Health (OIE), zoning is a risk management strategy for achieving the progressive control and eradication of animal diseases, and for providing guarantees for international trade. The implementation and effectiveness of zoning relies on the quality of Veterinary Services. Eradicating a disease and securing trading partners' recognition of this disease-free status demands resources, and promotes economic and fruitful development. It also guarantees the sanitary safety of trade, provided that OIE standards are applied and the World Trade Organization (WTO) Agreement on the Application of Sanitary and Phytosanitary Measures (SPS Agreement) is complied with. The OIE international standards and the SPS Agreement lay down provisions for the effective implementation of zoning and the recognition of disease-free zones. Although animal-disease-free statuses place such zones in a favourable position with regard to exporting their products to the international market, they can create internal restrictions between regions of the same country with differing statuses. As a general rule, each importing country implements its own evaluation procedure, independent of OIE official recognition. While this usually provides for information evaluation and an on-site inspection mission, there is no harmonisation between countries regarding the methodology or the information required for risk assessment. Recognition of a disease-free zone does not imply automatic permission to export any product from that zone. Firstly, it is necessary to request that the market be opened for each product in question, guaranteeing the conditions demanded by the target market (risk analysis and animal health certification). To benefit from external markets, there are ways of speeding up bilateral recognition of disease-free zones, such as bilateral veterinary agreements or free trade agreements that establish clear areas and procedures to be implemented by trading partner countries. The ongoing exchange of information among countries builds trust among their Veterinary Services and authorities, which leads to expedited recognition procedures. The work of the OIE (Pathway for the Evaluation of Performance of Veterinary Services [PVS Pathway], OIE Observatory) and the WTO Committee on Sanitary and Phytosanitary Measures (SPS Committee) (enforcement mechanisms) should be strengthened to assist countries in implementing zoning.

D'après l'Organisation mondiale de la santé animale (OIE), le « zonage ¼ est une stratégie de gestion du risque permettant d'avancer sur la voie du contrôle progressif des maladies animales et de leur éradication tout en fournissant des garanties dans le cadre des échanges internationaux. Sa mise en oeuvre et son efficacité sont tributaires de la qualité des Services vétérinaires. Si l'éradication réussie d'une maladie et la reconnaissance du statut indemne par les partenaires commerciaux mobilisent des ressources, elles constituent également une incitation majeure au développement productif et économique. En outre, elles garantissent la sécurité sanitaire des échanges internationaux, à condition d'appliquer les normes de l'OIE et de respecter les dispositions de l'Accord sur l'application des sanitaires et phytosanitaires (Accord SPS) de l'Organisation mondiale du commerce (OMC). L'OIE et l'Accord SPS établissent des dispositions pour la mise en oeuvre effective du « zonage ¼ et la reconnaissance des zones indemnes de maladies. Ce statut sanitaire place les zones qui en bénéficient en position favorable pour exporter leurs produits vers les marchés internationaux, mais il peut aussi entraîner des restrictions au niveau national par rapport aux zones du pays dotées d'un statut différent. Il est d'usage que chaque pays applique ses propres procédures indépendamment de la reconnaissance par l'OIE. Cela passe généralement par une évaluation de l'information fournie et par une mission d'inspection in situ, mais ni la méthodologie ni les informations requises pour mener à bien l'évaluation du risque n'ont fait l'objet d'une harmonisation de la part des pays. La reconnaissance d'une zone indemne ne vaut pas autorisation automatique d'exporter tout produit à partir de cette zone, car il faut encore, pour chaque produit, solliciter l'ouverture du marché et présenter des garanties démontrant que les conditions imposées par le marché de destination sont satisfaites (analyse du risque et certification sanitaire). Des méthodes existent pour bénéficier des marchés extérieurs en accélérant les reconnaissances bilatérales des zones indemnes de maladies ; il s'agit notamment des accords vétérinaires bilatéraux ou des accords de libre-échange, qui définissent clairement les cadres d'application et les procédures à mettre en place par les pays partenaires commerciaux. L'échange permanent d'informations entre les pays partenaires favorise la confiance entre leurs Services et Autorités vétérinaires respectifs, ce qui facilite d'autant ces procédures. Il convient de renforcer les travaux de l'OIE (Processus d'évaluation des performances des Services vétérinaires [Processus PVS], Observatoire des normes de l'OMC) et du Comité SPS de l'OMC (mécanismes d'évaluation de la conformité) afin d'aider les pays à mettre en oeuvre le « zonage ¼.

Según la Organización Mundial de Sanidad Animal (OIE), la «zonificación¼ es una estrategia de gestión del riesgo para avanzar en el control progresivo y la erradicación de enfermedades animales y para dar garantías al comercio internacional. Su implementación y eficacia dependen de la calidad de los Servicios Veterinarios. Erradicar una enfermedad y lograr el reconocimiento de tal situación por parte de socios comerciales implica recursos e incentiva el desarrollo productivo y económico. También garantiza la seguridad sanitaria del comercio siempre que se apliquen las normas de la OIE y se respete el Acuerdo sobre la Aplicación de Medidas Sanitarias y Fitosanitarias de la Organización Mundial del Comercio (OMC) (Acuerdo MSF). Las normas internacionales de la OIE y el Acuerdo MSF establecen disposiciones para una implementación efectiva de la «zonificación¼ y el reconocimiento de zonas libres de enfermedades. Este estatus sanitario posiciona favorablemente a dichas zonas para exportar sus productos al mercado internacional, pero puede generar restricciones internas respecto a regiones del mismo país con estatus diferentes. Lo habitual es que cada país aplique un proceso propio, independientemente del reconocimiento de la OIE. En general, contemplan una evaluación de la información y una misión de inspección in situ, pero no existe una armonización entre países ni respecto a la metodología ni respecto a la información requerida para la evaluación de riesgos. Este reconocimiento no implica el permiso automático para exportar cualquier producto desde esa zona, sino que se debe solicitar la apertura del mercado para cada producto en cuestión garantizando las condiciones exigidas por el mercado de destino (análisis del riesgo y certificación sanitaria). Para beneficiarse de los mercados externos, existen formas de agilizar los reconocimientos bilaterales de las zonas libres de enfermedades, como los acuerdos bilaterales veterinarios o los Acuerdos de Libre Comercio, mediante los cuales se establecen ámbitos y procedimientos claros a implementar por parte de los países socios comerciales. El intercambio de información permanente entre los países genera confianza entre sus Servicios y Autoridades Veterinarias, lo cual redunda en la agilización de estos procesos. Se debe reforzar el trabajo de la OIE (Proceso de Prestaciones de los Servicios Veterinarios [Proceso PVS], Observatorio de la OIE) y del Comité MSF de la OMC (mecanismos de observancia) para ayudar a los países a implementar la «zonificación¼.

Efficacy of self-administered complex decongestive therapy on breast cancer-related lymphedema: a single-blind randomized controlled trial.

PURPOSE: After surgery, breast cancer-related lymphedema (BCRL) is a frequent chronic condition. The complex decongestive therapy (CDT) delivered by physiotherapists at hospitals is the state-of-the-art treatment choice. As lymphedema requires continuous management, we designed a 1-month-long course to train women to professionally carry out a self-administered CDT (saCDT) and tested its efficacy while keeping the benefits of CDT. METHODS: Consecutive patients treated with CDT over a 1-year period at an Italian facility were randomly assigned to either experimental (EXP, saCDT course) or control (CTRL, usual care) group. Women were assessed before, at 1, and 6 months from enrolment. Pain assessed by the numerical pain rating scale (NPRS) was the primary outcome. Arm asymmetry assessed by the excess limb volume (ELV) was the secondary outcome. Outcome variations were compared to their MCID to classify women as improved, stable, or worsened. RESULTS: Forty-one women were included. The proportion of stable or improved women was significantly different between EXP and CTRL groups at 6 months after enrolment for both arm pain (p = 0.01) and asymmetry (p < 0.01). Noteworthy, only one EXP woman had worsened after 6 months. NPRS significantly decreased in the EXP group only, with a median variation of 2 points. Arm ELV significantly decreased with respect to the baseline value in the EXP group only, with a median reduction of 8%. CONCLUSIONS: Teaching saCDT to women with BCRL is effective in maintaining or improving the benefits of CDT and can be used as a self-care tool in the management of BCRL.

Evidence-Based Medicine and Clinical Practice: the first Italian attempt to define the appropriateness of rehabilitation admission criteria through the application of the Delphi method.

BACKGROUND: One of the consequences of today's global economic crisis is the need to control healthcare spending, in particular by improving the level of appropriateness. Thus, admission to rehabilitation has become an issue, especially as regards inappropriateness of resource allocation. The scientific literature suggests that more attention should be paid to the problem of clinical appropriateness in order to better identify the patients' actual needs. For the first time in Italy, this study aims at defining the appropriateness of intensive rehabilitation admission criteria through use of the Delphi method involving a panel of national experts. MATERIAL AND METHODS: A three-round Delphi survey was conducted according to international guidelines. Electronic questionnaires were individually sent via e-mail to ensure the participants' anonymity throughout the process. Questions were mostly based on rehabilitation literature. RESULTS: During the Delphi process, a total of 79 items were submitted to a heterogenous panel of rehabilitation experts who were asked to express their level of agreement to the item contents on a five-point Likert scale. At the end of the survey, a list of 19 appropriate criteria for admission to intensive rehabilitation facilities and 21 reasons for inappropriateness was drawn up. CONCLUSION: This study represents the first attempt in Italy to define shared and objective appropriateness criteria for admission to intensive rehabilitation. Out of the total number of experts invited to participate (31), only 16 completed the entire survey. This poor participation rate unfortunately demonstrates the lack of awareness among Italian rehabilitation professionals, which is a further sign of both the scarcity of scientific evidence in this area and the need to reach consensus on admission criteria.

Boron nitride nanomaterials: biocompatibility and bio-applications.

Boron nitride has structural characteristics similar to carbon 2D materials (graphene and its derivatives) and its layered structure has been exploited to form different nanostructures such as nanohorns, nanotubes, nanoparticles and nanosheets. Unlike graphene and other carbon based 2D materials, boron nitride has a higher chemical stability. Owing to these properties, boron nitride has been used in different applications as a filler, lubricant and as a protective coating. Boron nitride has also been applied in the biomedical field to some extent, but far less than other 2D carbon materials. This review explores the potential of boron nitride for biomedical applications where the focus is on boron nitride biocompatibility in vivo and in vitro, its applicability as a coating material/composite and its anti-bacterial properties. Geometry, material processing and the type of biological analysis appear to be relevant parameters in assessing boron nitride bio-compatibility. Engineering of both these variables and the coating would open the door for some applications in the medical field for boron nitride, such as drug delivery, imaging and cell stimulation.

Muscle Shortening and Spastic Cocontraction in Gastrocnemius Medialis and Peroneus Longus in Very Young Hemiparetic Children.

OBJECTIVES: Muscle shortening and spastic cocontraction in ankle plantar flexors may alter gait since early childhood in cerebral palsy (CP). We evaluated gastrosoleus complex (GSC) length, and gastrocnemius medialis (GM) and peroneus longus (PL) activity during swing phase, in very young hemiparetic children with equinovalgus. METHODS: This was an observational, retrospective, and monocentric outpatient study in a pediatric hospital. Ten very young hemiparetic children (age 3 ± 1 yrs) were enrolled. These CP children were assessed for muscle extensibility (Tardieu scale XV1) in GSC (angle of arrest during slow-speed passive ankle dorsiflexion with the knee extended) and monitored for GM and PL electromyography (EMG) during the swing phase of gait. The swing phase was divided into three periods (T1, T2, and T3), in which we measured a cocontraction index (CCI), ratio of the Root Mean Square EMG (RMS-EMG) from each muscle during that period to the peak 500 ms RMS-EMG obtained from voluntary plantar flexion during standing on tiptoes (from several 5-second series, the highest RMS value was computed over 500 ms around the peak). RESULTS: On the paretic side: (i) the mean XV1-GSC was 100° (8°) (median (SD)) versus 106° (3°) on the nonparetic side (p = 0.032, Mann-Whitney); (ii) XV1-GSC diminished with age between ages of 2 and 5 (Spearman, ρ = 0.019); (iii) CCIGM and CCIPL during swing phase were higher than on the nonparetic side (CCIGM, 0.32 (0.20) versus 0.15 (0.09), p < 0.01; CCIPL, 0.52 (0.30) versus 0.24 (0.17), p < 0.01), with an early difference significant for PL from T1 (p = 0.03). CONCLUSIONS: In very young hemiparetic children, the paretic GSC may rapidly shorten in the first years of life. GM and PL cocontraction during swing phase are excessive, which contributes to dynamic equinovalgus. Muscle extensibility (XV1) may have to be monitored and preserved in the first years of life in children with CP. Additional measurements of cocontraction may further help target treatments with botulinum toxin, especially in peroneus longus.

A statistical approach to discriminate between non-fallers, rare fallers and frequent fallers in older adults based on posturographic data.

BACKGROUND: Identification of future non-fallers, infrequent and frequent fallers among older people would permit focusing the delivery of prevention programs on selected individuals. Posturographic parameters have been proven to differentiate between non-fallers and frequent fallers, but not between the first group and infrequent fallers. METHODS: In this study, postural stability with eyes open and closed on both a firm and a compliant surface and while performing a cognitive task was assessed in a consecutive sample of 130 cognitively able elderly, mean age 77(7)years, categorized as non-fallers (N=67), infrequent fallers (one/two falls, N=45) and frequent fallers (more than two falls, N=18) according to their last year fall history. Principal Component Analysis was used to select the most significant features from a set of 17posturographic parameters. Next, variables derived from principal component analysis were used to test, in each task, group differences between the three groups. FINDINGS: One parameter based on a combination of a set of Centre of Pressure anterior-posterior variables obtained from the eyes-open on a compliant surface task was statistically different among all groups, thus distinguishing infrequent fallers from both non-fallers (P<0.05) and frequent fallers (P<0.05). INTERPRETATION: For the first time, a method based on posturographic data to retrospectively discriminate infrequent fallers was obtained. The joint use of both the eyes-open on a compliant surface condition and this new parameter could be used, in a future study, to improve the performance of protocols and to verify the ability of this method to identify new-fallers in elderly without cognitive impairment.

Assessment of waveform similarity in clinical gait data: the linear fit method.

The assessment of waveform similarity is a crucial issue in gait analysis for the comparison of kinematic or kinetic patterns with reference data. A typical scenario is in fact the comparison of a patient's gait pattern with a relevant physiological pattern. This study aims to propose and validate a simple method for the assessment of waveform similarity in terms of shape, amplitude, and offset. The method relies on the interpretation of these three parameters, obtained through a linear fit applied to the two data sets under comparison plotted one against the other after time normalization. The validity of this linear fit method was tested in terms of appropriateness (comparing real gait data of 34 patients with cerebrovascular accident with those of 15 healthy subjects), reliability, sensitivity, and specificity (applying a cluster analysis on the real data). Results showed for this method good appropriateness, 94.1% of sensitivity, 93.3% of specificity, and good reliability. The LFM resulted in a simple method suitable for analysing the waveform similarity in clinical gait analysis.

[Lung eosinophilic syndrome: clinical presentation and cases report]. / Síndrome de eosinofília pulmonar presentación clínica y serie de casos.

INTRODUCTION: Pulmonary eosinophilia syndrome is characterized by a group of diseases that present clinical-radiological conditions, pulmonary eosinophilia or peripheral lung parenchyma in its evolution. We described the clinical and radiological presentation. METHODS: Retrospective descriptive analysis of medical records of 7 patients between 2007 and 2010. RESULTS: The highest numbers of cases were observed in women, with peripheral eosinophilia with values between 550 and 10,000 cells/mm3. The more frequent signs and symptoms were cough, dyspnea, fever and wheezing. The more prevalent radiological findings were alveolar interstitial and alveolar pattern. At CT scan, the most frequent pattern was ground glass. The main diagnoses made were acute and chronic eosinophilic pneumonia in equal proportions, both with response to steroids. CONCLUSIONS: The pulmonary eosinophilia syndrome shares common features with clinical and radiological entities most prevalent, particularly community-adquired pneumonia.

Introducción: El síndrome de eosinofilia pulmonar se caracteriza por un grupo de patologías que presentan afección clínico ­ radiológica pulmonar con eosinofilia periférica o en parénquima pulmonar en su evolución. Materiales y métodos: Se describen las características de presentaciones clínico-radiológicas y evolutivas de pacientes atendidos entre 2007 y 2010 en Hospital Rawson. Resultados: Sobre 8 casos, se observó mayor número de casos en mujeres. Los signos y síntomas principales fueron tos, disnea, fiebre y sibilancias. Los hallazgos radiológicos más prevalentes fueron patrón alveolar y alveolointersticial. En la TAC el más frecuente fue el patrón en vidrio esmerilado. La eosinofilia periférica presentó valores entre 550 y 10.000 cel/mm3. Los pacientes fueron abdordados inicialmente como neumonía adquirida en la comunidad en el 62% de los casos. Los diagnósticos principales realizados fueron neumonía eosinofílica aguda y crónica, ambas con respuesta a esteroides. Conclusiones: El síndrome de eosinofilias pulmonares comparte características clínico-radiológicas comunes con entidades de mayor prevalencia, particularmente NAC.

Síndrome de eosinofília pulmonar presentación clínica y serie de casos / [Lung eosinophilic syndrome: clinical presentation and cases report].

INTRODUCTION: Pulmonary eosinophilia syndrome is characterized by a group of diseases that present clinical-radiological conditions, pulmonary eosinophilia or peripheral lung parenchyma in its evolution. We described the clinical and radiological presentation. METHODS: Retrospective descriptive analysis of medical records of 7 patients between 2007 and 2010. RESULTS: The highest numbers of cases were observed in women, with peripheral eosinophilia with values between 550 and 10,000 cells/mm3. The more frequent signs and symptoms were cough, dyspnea, fever and wheezing. The more prevalent radiological findings were alveolar interstitial and alveolar pattern. At CT scan, the most frequent pattern was ground glass. The main diagnoses made were acute and chronic eosinophilic pneumonia in equal proportions, both with response to steroids. CONCLUSIONS: The pulmonary eosinophilia syndrome shares common features with clinical and radiological entities most prevalent, particularly community-adquired pneumonia.

High evolutionary dynamism in 5S rDNA of fish: state of the art.

The 5S ribosomal DNA (rDNA) consists of one transcriptional unit of about 120 base pairs, which is separated from the next unit by a non-transcribed spacer (NTS). The coding sequence and the NTS together form a repeat unit which can be found in hundreds to thousands of copies tandemly repeated in the genomes. The NTS regions seem to be subject to rapid evolution. The first general model of evolution of these multigene families was referred to as divergent evolution, based on studies using hemoglobin and myoglobin as model systems. Later studies showed that nucleotide sequences of different multigene family members are more closely related within species than between species. This observation led to a new model of multigene family evolution, termed concerted evolution. Another model of evolution, named the birth-and-death model, has been found to be more suitable to explain the long-term evolution of these multigene families. According to this model, new genes originate by successive duplications, and these new genes are either maintained for a long time or are lost, or else degenerate into pseudogenes. In this review we describe different sources of variability in the 5S rDNA genes observed in several distinct fish species. This variability is mainly referred to NTSs and includes the presence of other multigene families (mainly LINEs, SINEs, non-LTR retrotransposons, and U snRNA families). Different types of microsatellites have also been found to contribute to the increase of variability in this region. Our recent results suggest that horizontal transfer contributes to the increase of diversity in the NTSs of some species. Variability in the 5S rDNA coding region affecting the stability of the structure, but without effects on the function of the 5S rRNA, is also described. Retrotransposons seem to be responsible for the high dynamism of 5S rDNA, while microsatellites acting as recombination hot spots could stabilize a wide variety of unusual DNA structures, affecting DNA replication and enhancing or decreasing promoter activity in gene expression. The relationship between the high variability found at molecular level and the low variability found at chromosomal level is also discussed.

Upper limb evaluation with robotic exoskeleton. Normative values for indices of accuracy, speed and smoothness.

BACKGROUND: Robotic rehabilitation devices for upper limb function (ULF) provide global indicators of a patient's ability, but the temporal evolution of motion related to motor control is disregarded. OBJECTIVE: To determine normative values for indices of accuracy, speed and smoothness in the evaluation of upper limb function. METHODS: Twenty-five healthy individuals performed the Armeo®Spring device "Vertical Capture" task. Custom stand-alone software was developed to provide the following indices: global Hand Path Ratio (HPR), local HPR in the target area (locHPR), vertical and horizontal overshoot (vertOS, horOS), maximum and mean velocity (maxVel, meanVel), mean/maximum velocity, number of peaks in velocity profiles (NVelPeaks) and normalized jerk (NormJerk). The dependence of indices on task characteristics was analyzed by an ANCOVA test. Indices inner relationships were assessed by a correlation and a factor analysis. Normative values were then provided. RESULTS: 4,268 single reaching movements were analyzed. Four indices were not affected by movement direction. Indices were minimally influenced by the difficulty level. Based upon correlation and factor analysis indices and can be grouped into three assessment fields, dealing with precision, velocity and smoothness. CONCLUSIONS: We have developed a tool to assess ULF in dynamic condition. Normative values were obtained to be used as references in assessing patients.

A method to differentiate the causes of stiff-knee gait in stroke patients.

Stiff-knee gait (SKG) is a common abnormal gait pattern in patients after stroke characterized by insufficient knee flexion (KF) during swing. Overactivity of the rectus femoris (RF) is considered the primary cause of SKG. Inadequate push-off has been indicated as an additional cause in the recent literature, as KF depends on knee flexion velocity in preswing (KFV). We used the peak of vertical acceleration of the malleolus (PMVA) as a kinematic-based indirect measure of push-off and studied its relationship with KF and KFV in a sample of 20 healthy subjects walking fast (v = 95 ± 5%heights(-1)), at self-selected speed (v = 74 ± 5%heights(-1)), slow (v = 54 ± 6%heights(-1)) and very slow (v = 38 ± 5%heights(-1)) and in a sample of 52 stroke patients with SKG (age 60 ± 11, v = 20 ± 11%heights(-1)). In healthy subjects PMVA occurred before knee flexion acceleration (p<0.001) and hip flexion acceleration (p<0.001). KF appeared as a bottom-up mechanism driven by the ankle push-off. From a regression analysis, the PMVA-KFV cause-effect relationship resulted strictly linear, with R(2) = 0.967, KFV = 0+7.1×PMVA, P<0.0001. Data from SKG patients were compared to this normal cause-effect model. For 44/52 patients the reduced KFV was combined with lack of push-off. Data from 8/52 patients only were statistically outside the 95%CI of the model, thus requiring for a braking mechanism to explain KFV reduction. In stroke adults of our sample the push-off impairment (85% of cases) and not the inappropriate knee extension moment produced by the thigh muscles was the primary cause of SKG. This result could explain the low average efficacy (<10°) of focal and surgical treatments at the quadriceps. The presented model could be used to differentiate the primary cause of SKG between inadequate push-off and braking activity of the thigh muscles, thus increasing the effectiveness of the selected treatment.

Inter-laboratory consistency of gait analysis measurements.

The dissemination of gait analysis as a clinical assessment tool requires the results to be consistent, irrespective of the laboratory. In this work a baseline assessment of between site consistency of one healthy subject examined at 7 different laboratories is presented. Anthropometric and spatio-temporal parameters, pelvis and lower limb joint rotations, joint sagittal moments and powers, and ground reaction forces were compared. The consistency between laboratories for single parameters was assessed by the median absolute deviation and maximum difference, for curves by linear regression. Twenty-one lab-to-lab comparisons were performed and averaged. Large differences were found between the characteristics of the laboratories (i.e. motion capture systems and protocols). Different values for the anthropometric parameters were found, with the largest variability for a pelvis measurement. The spatio-temporal parameters were in general consistent. Segment and joint kinematics consistency was in general high (R2>0.90), except for hip and knee joint rotations. The main difference among curves was a vertical shift associated to the corresponding value in the static position. The consistency between joint sagittal moments ranged form R2=0.90 at the ankle to R2=0.66 at the hip, the latter was increasing when comparing separately laboratories using the same protocol. Pattern similarity was good for ankle power but not satisfactory for knee and hip power. The force was found the most consistent, as expected. The differences found were in general lower than the established minimum detectable changes for gait kinematics and kinetics for healthy adults.

EGFRvIII gene rearrangement is an early event in glioblastoma tumorigenesis and expression defines a hierarchy modulated by epigenetic mechanisms.

Amplification and rearrangements of the epidermal growth factor receptor (EGFR) gene are frequently found in glioblastoma multiforme (GBM). The most common variant is EGFR variant III (EGFRvIII). Research suggests that EGFRvIII could be a marker for a cancer stem cell or tumor-initiating population. If amplification and rearrangement are early events in tumorigenesis, this implies that they should be preserved throughout the tumor. However, in primary GBM, EGFRvIII expression is focal and sporadic. Unexpectedly, we found EGFR amplification and rearrangement throughout the tumor, including regions with no EGFRvIII expression, suggesting that mechanisms exist to modulate EGFRvIII expression even in the presence of high gene amplification. To study this phenomenon, we characterized three GBM cell lines with endogenous EGFRvIII. EGFRvIII expression was heterogeneous, with both positive and negative populations maintaining the genetic alterations, akin to primary tumors. Furthermore, EGFRvIII defined a hierarchy where EGFRvIII-positive cells gave rise to additional positive and negative cells. Only cells that had recently lost EGFRvIII expression could re-express EGFRvIII, providing an important buffer for maintaining EGFRvIII-positive cell numbers. Epigenetic mechanisms had a role in maintaining heterogeneous EGFRvIII expression. Demethylation induced a 20-60% increase in the percentage of EGFRvIII-positive cells, indicating that some cells could re-express EGFRvIII. Surprisingly, inhibition of histone deacetylation resulted in a 50-80% reduction in EGFRvIII expression. Collectively, this data demonstrates that EGFR amplification and rearrangement are early events in tumorigenesis and EGFRvIII follows a model of hierarchical expression. Furthermore, EGFRvIII expression is restricted by epigenetic mechanisms, suggesting that drugs that modulate the epigenome might be used successfully in glioblastoma tumors.