Sifilides elegantes de BROCQ en una paciente con SIDA y sífilis secundaria. Presentación de un caso y revisión de la literatura / 5 BROCQ ELEGANTS SYPHILIDES IN A PATIENT WITH AIDS AND SECONDARY SYPHILLIS

La coinfección entre el Treponema pallidum y el virus de la inmunodeiciencia humana (VIH) altera el curso clínico clásico de la sífilis aumentando la probabilidad de aparición de formas atípicas del secundarismo sifilítico. Entre estas formas se ha descripto a la sífilis elegante, entidad caracterizada por un exantema maculopapuloso descamativo, de aspecto anular, por lo general, con indemnidad de las regiones palmo plantar y de las mucosas. Se presenta un caso de sífilis secundaria, con lesiones típicas por su aspecto y localización, de sifílides elegantes en una paciente con diagnóstico de sida

Co-infection between Treponema pallidum and HIV alters the classic clinical course of syphilis, increasing the likelihood of atypical forms of syphilitic secondaryism. Among these forms, elegant syphilis has been described, an entity characterized by a desquamating maculopapular rash of annular appearance, with indemnity of the palmoplantar surface and mucous regions. Here, we present a case of secondary syphilis with typical lesions of elegant syphillides, in a patient diagnosed with AIDS

Respuesta paradojal al tratamiento antituberculoso en una paciente con SIDA / PARODOXICAL RESPONSE TO ANTITUBERCULOSE TREATMENT IN A PATIENT WITH AIDS

La tuberculosis (TB) es una enfermedad infectocontagiosa de gran importancia en la salud pública y representa una de las 10 principales causas de muerte a nivel mundial. Una de las complicaciones del tratamiento antituberculoso es la respuesta paradojal, que se define como un empeoramiento clínico o la aparición de nuevas lesiones en un paciente que comienza un tratamiento antifímico. Esta reacción está mediada por una respuesta de hipersensibilidad a los antígenos de Mycobacterium tuberculosis. Suele aparecer entre 2 y 4 meses luego de iniciado el tratamiento antituberculoso, generalmente precedida por una mejoría inicial del cuadro. Se presenta una mujer con sida y tuberculosis ganglionar con respuesta paradojal a la terapéutica antimicobacteriana y se realiza una revisión bibliográfica del tema.

Tuberculosis (TB) is an infectious disease of great importance in public health and represent one of the 10 leading causes of death worldwide. One of the complication of the antituberculous treatment is the paradoxical reaction, which is defined as a worsening or the appearance of new lesions in a patient receiving antimicobacterial treatment. This paradoxical response is mediated by a hypersensitivity reaction to mycobacterial antigens. It usually appears between 2 and 4 months after initiation of tuberculosis treatment and is preceded by an initial improvement of the clinical condition. Here, we describe a woman with AIDS and lymph node tuberculosis with a paradoxical reaction to antimycobacterial therapy and the subject is reviewed.

Leishmaniasis visceral en paciente infectado con VIH / VISCERAL LEISHMANIASIS IN PATIENTS INFECTED WITH AIDS

La coinfección entre el virus de la inmunodeficiencia humana (VIH) y la Leishmaniosis visceral (LV) ha sido descripta de manera reciente, en especial en Brasil y en ciertas áreas de la Europa del Mediterráneo. Los pacientes VIH positivos con fiebre de origen desconocido y/o citopenias tienen indicación de punción aspirativa de médula ósea para estudios microbiológicos e histopatológicos, estos últimos para descartar un síndrome linfoproliferativo. El diagnóstico de leishmaniosis visceral puede confirmarse por diversas técnicas microbiológicas y serológicas: detección de amastigotes de Leishmania en aspirados de médula ósea con tinción de Giemsa, detección de anticuerpos por aglutinación directa, inmunofluorescencia indirecta, detección del antígeno rK39, reacción en cadena de la polimerasa en extendidos de médula ósea y prueba de aglutinación del látex. La LV puede ser la primera manifestación del sida o ser una complicación grave en pacientes ya diagnosticados con VIH e inmunodeficiencia severa. La LV es una complicación grave y potencialmente fatal y debe sospecharse en todo sujeto VIH positivo con fiebre de etiología desconocida y/o citopenias.

The association between visceral leishmaniasis (VL) and HIV is recent and has an increasing number of cases in Brazil and worldwide - especially in the Mediterranean region of Europe. HIV patients with cytopenias and/or fever of an unknown etiology, have indication of bone marrow aspirate for microbiological cultures and histopathological examination to rule out lymphoproliferative disorders. Diagnosis of VL can be confirmed by the following examinations: Leishmania amastigotes detection in bone marrow aspirate with Giemsa smear, direct agglutination test, indirect immunofluorescence, rK39 dipstick test, polymerase chain reaction and latex agglutination test. VL may be the first infection related with HIV or patients can be diagnosed with VL concomitantly with AIDS. HIV/AIDS-associated VL is an aggressive complication with a potentially fatal evolution in advanced HIV/AIDS patients, without specific symptoms, that should be suspected in all HIV subjects with fever of unknown etiology and cytopenias.

Parvovirus B19: un nuevo patógeno emergente en pacientes con SIDA. Presentación de 3 casos / PARVOVIRUS B19: HUMAN PARVOVIRUS B19: A NEW EMERGING DISEASE IN PATIENTS WITH AIDS. REPORT OF THREE PATIENTS

El Parvovirus humano B19 puede presentarse con una amplia variedad de manifestaciones clínicas, con distinto compromiso y evolución según el huésped afectado. En pacientes inmunocomprometidos se asocia con cuadros hematológicos prolongados y graves. Se describen 3 casos de pacientes con antecedentes de infección por virus de la inmunodeficiencia humana (VIH) que desarrollaron infecciones agudas por Parvovirus B19 que se presentaron con síndrome febril, citopenias (anemia, plaquetopenia y disminución de reticulocitos) y esplenomegalia. En todos los casos el diagnóstico se confirmó por la serología específica. Todos recibieron tratamiento con inmunoglobulina humana (Ig) intravenosa (IV); 2 pacientes tuvieron buena respuesta clínica y mejoría de citopenias mientras que el restante falleció. La infección por Parvovirus B19 debe incluirse en el diagnóstico diferencial de los pacientes VIH positivos con fiebre y citopenias, principalmente anemia persistente y compromiso linfoganglionar con esplenomegalia

Human Parvovirus B 19 is presented as a variety of diseases with different compromise and evolution according to the affected host. In immunocompromised patients the acute infection due to Parvovirus B19 is associated with severe and prolonged hematological clinical pictures. Three cases of patients with a history of infection with human immunodeficiency virus (HIV) co-infected with Human Parvovirus B19 are presented. All of they presented with febrile syndrome, cytopenias (anemia, platelet count and reticulocyte reduction) and lymphadenopathy and splenomegaly. In all cases the diagnosis was confirmed by serology. All were treated with intravenous human immunoglobulin (IVI G; 2 patients had good clinical response and better cytopenias while the other died. We consider thinking about Parvovirus B19 infection in HIV immunocompromised hosts with haematological involvement, mainly persistent anemia and lymph node involvement with splenomegaly

Advancements in AAV-mediated Gene Therapy for Pompe Disease.

Pompe disease (glycogen storage disease type II) is caused by mutations in acid α-glucosidase (GAA) resulting in lysosomal pathology and impairment of the muscular and cardio-pulmonary systems. Enzyme replacement therapy (ERT), the only approved therapy for Pompe disease, improves muscle function by reducing glycogen accumulation but this approach entails several limitations including a short drug half-life and an antibody response that results in reduced efficacy. To address these limitations, new treatments such as gene therapy are under development to increase the intrinsic ability of the affected cells to produce GAA. Key components to gene therapy strategies include the choice of vector, promoter, and the route of administration. The efficacy of gene therapy depends on the ability of the vector to drive gene expression in the target tissue and also on the recipient's immune tolerance to the transgene protein. In this review, we discuss the preclinical and clinical studies that are paving the way for the development of a gene therapy strategy for patients with early and late onset Pompe disease as well as some of the challenges for advancing gene therapy.

Estimating the real burden of cardiovascular mortality in diabetes.

OBJECTIVE: To compare different methods assessing the burden of cardiovascular mortality in diabetes mellitus, which is usually underestimated by standard mortality statistics based on the underlying cause of death. PATIENTS AND METHODS: All residents in the Veneto Region (Italy) aged 30-89 years with co-payment exemption for diabetes in January 2010 (n=185,341) were identified and linked with mortality records (2010-2015). The underlying causes of death, as well as all the diseases mentioned in the death certificate (multiple causes), were extracted. The standardized mortality ratios (SMR) were computed with regional rates as a reference. RESULTS: After grouping diabetes and circulatory diseases as the underlying cause of death, the mortality rates were highly increased, especially among patients aged 30-54 years: SMR 4.24 (95% confidence interval 3.57-5.00) and 9.84 (7.47-12.72) in males and females, respectively. After re-assignment of the underlying cause in deaths from diabetes, the percentage of overall mortality caused by circulatory diseases increased from 33.8% to 41.7%. Based on multiple causes, the risk of death was increased for several cardiovascular diseases, including causes rarely emerging from standard mortality statistics such as atrial fibrillation/flutter. CONCLUSIONS: The re-assignment of the underlying cause and the analyses of the multiple causes of death allowed to estimate the whole burden of mortality associated with cardiovascular diseases.

El ateneo como estrategia de educación médica continua. Del mito griego al hospital de hoy. / Athenaeum as a strategy of continuous medical education. From the greek myth to the hospital today

La educación médica continua se define como el conjunto de acciones y recursos dirigidos a cambiar las conductas de los profesionales para mejorar los resultados de su actividad asistencial diaria frente a los pacientes. O bien, toda acción que realiza un médico para seguir aprendiendo y permanecer actualizado, una vez finalizada su formación universitaria. Las estrategias para conseguir tal fin, son la realización de cursos, la ra congresos y/o jornadas, las actividades hospitalarias (recorridas de sala, supervisión y ateneos), la lectura y discusión de artículos biomédicos en internet o en publicaciones en papel en el denominado ateneo bibliográfico, el intercambio con colegas, la consulta con otros profesionales y los cursos a distancia. En el presente artículo, se plantea el ejercicio del ateneo como una de las principales fuentes de aprendizaje al proponer una verdadera reflexión sobre la práctica profesional (AU)

Continuing medical education is defined as the set of actions and resources aimed at changing the behavior of professionals to improve the results of their daily care activity in front of patients. Or, any action that a doctor performs to continue learning and remain updated, once his university education is completed. The strategies to achieve this goal are the completion of courses, the attendance at conferences and/or conferences, hospital activities (visits to the ward, supervision and athenaeums), the reading and disicussion of biomedical articles on the internet or in publications on paper. The so-called bibliographic athenacum, the exchange with colleagues, the consultations with other professionals and the distance courses. In the present article, the exercise of the athenaemum is considered as one of the main sources of learning by proposing a true reflection on professional practice (AU)

Development of an integrated chromatographic system for ω-transaminase-IMER characterization useful for flow-chemistry applications.

An integrated chromatographic system was developed to rapidly investigate the biocatalytic properties of ω-transaminases useful for the synthesis of chiral amines. ATA-117, an (R)-selective ω-transaminase was selected as a proof of concept. The enzyme was purified and covalently immobilized on an epoxy monolithic silica support to create an immobilized enzyme reactor (IMER). Reactor efficiency was evaluated in the conversion of a model substrate. The IMER was coupled through a switching valve to an achiral analytical column for separation and quantitation of the transamination products. The best conditions of the transaminase-catalyzed bioconversion were optimized by a design of experiments (DoE) approach. The production of (R)-1-(4-methoxyphenyl)propan-2-amine and (R)-1-methyl-3-phenylpropylamine, intermediates for the synthesis of the bronchodilator formoterol and the antihypertensive dilevalol respectively, was achieved in the presence of different amino donors. The enantiomeric excess (ee) was determined off-line by developing a derivatization procedure using Nα-(2,4-dinitro-5-fluorophenyl)-L-alaninamide reagent. The most satisfactory conversion yields were 60% for (R)-1-(4-methoxyphenyl)propan-2-amine and 29% for (R)-1-methyl-3-phenylpropylamine, using isopropylamine as amino donor. The enantiomeric excess of the reactions were 84%R and 99%R, respectively.

Factores asociados con la indicación de la profilaxis pre-exposición para HIV en médicos de Argentina / Associated factors with the indication for HIV prevention of pre-exposure prophylaxis for argentinian physicians

La profilaxis pre-exposición (PrEP) es una medida eficaz para la prevención de la transmisión del VIH. Con la implementación de la misma, algunos estudios señalan una reducción en la transmisión superior al 90%, cuando la adherencia es alta. Sin embargo, el uso de Emtricitabina/ Tenofovir alafenamida (FTC/TDF) en la Argentina aún no esta aprobado por las autoridades regulatorias. En profesionales de Argentina el conocimiento, aval y factores asociados con la prescripción de la PrEP no ha sido evaluada. Este es un estudio de corte transversal mediante una encuesta on line realizada en Agosto de 2017. La misma fue distrubuida entre profesionales de Argentina y valoró diferentes aspectos de la PrEP (conocimiento, aval e indicación de la misma). Los resultados obtenidos se expresaron en frecuencias y porcentajes. Para las asociaciones entre variables categóricas se realizó un análisis univariado (test de chi2 ) y de regresión logística binaria. Se consideró como significativo, un valor de p < 0.05. La encuesta fue realizada por 238 profesionales pertenecientes a 81 centros asistenciales. Los escenarios clínicos donde se observó mayor predisposición a la indicación de PrEP fueron: parejas discordantes (77%), trabajadores/as sexuales (61%), pacientes transgénero (32%), adictos a drogas intravenosas (31%), hombres que mantienen sexo con otros hombres (HSH) (23%). Los factores asociados con la prescripción de PrEP fueron: cargo asistencial de jefe de servicio (p<0.05), médicos especialistas en enfermedades infecciosas (p<0.05), atención de más de 200 pacientes seropositivos para el virus de la inmunodeficiencia humana (VIH) por año (p<0.009), prescripción previa de profilaxis post-exposición (p<0.008). Los autores concluyen señalando que, a pesar de no estar aprobado por los entes regulatorios, la PrEP ha sido prescripta off label por profesionales de Argentina. Entre ellos, aquellos que adoptaron la prescripción fueron los que mostraron mayor experiencia en la atención de pacientes VIH positivos, jefes/as de servicio y especialistas en infectología. Estos resultados podrían ser utilizados en un futuro para impulsar nuevas herramientas de prevención en la transmisión de VIH

Pre-exposure prophylaxis (PrEP) is an effective measure to prevent HIV transmission. If the adherence is high, transmission rates are reduced by more than 90%. In Argentina, FTC-TDF is not yet approved for PrEP by the local regulatory agency.  PrEP  awareness,  PrEP  adoption, and factors associated with adoption among argentine physicians had not been studied to date. We designed a cross-sectional online survey conducted in August 2017 among argentine physicians and valored differents items about PrEP, (knowledge, attitudes, and beliefs associated with adoption). Univariate analysis was performed; the associations between categorical variables were analyzed by means of the chi2  test. The level of significance was considered with p <0.05. A total of 238 surveys were received from 81 centers in Argentina. Clinical scenarios associated with the highest prescription were: serodiscordant couples 77%, sex workers 61%, transgender patients 32%, people who inject drugs 31%, and men who have sex with men (MSM) 23%. Factors associated with PrEP prescription between physicians were been chief of staff (p<0.05), been an infectious diseases specialist (p<0.05), assist more than 200 HIV seropositive patients per year (p<0.009) and having prescribed postexposure prophylaxis (PEP) (p<0.008). The authors concluded that in spite of not yet approved by the local regulatory agency, PrEP is been prescribed off- label by argentine physicians. Adopters were more likely to have experience providing HIV care, been chief of staff and ID specialist. These results could be used to plan future HIV prevention strategies in Argentina.

Síndrome de Sweet asociado a infección por el Virus de la Inmunodeficiencia Humana / Sweet's syndrome associated to human immunodeficiency virus infection

El síndrome de Sweet es una dermatosis neutrofílica aguda y febril que puede ser desencadenada por diferentes noxas. El diagnóstico es clínico a partir de una dermatosis aguda, con fiebre, leucocitosis y lesiones cutáneas localizadas en cara, cuello y extremidades. La histopatología muestra un denso infiltrado inflamatorio de la dermis a predominio neutrofílico, sin signos de vasculitis. Se presenta un paciente con síndrome de Sweet asociado a infección por el virus de la inmunodeficiencia humana

Sweet's syndrome associated with human immunodeficiency virus infection Sweet's syndrome is a neutrophilic and acute febrile dermatosis that can be triggered by different noxas. Diagnosis should be suspected in a patient with fever, leukocytosis and cutaneous lesions located on the face, the neck and the extremities. Cutaneous biopsy confirms the diagnosis of Sweet syndrome, with typical features of a neutrophilic dermatosis in the absence of vasculitis. Here we present a case of Sweet syndrome associated with human immunodeficiency virus infection

Mortality from infectious diseases in diabetes.

BACKGROUND AND AIMS: To investigate the risk of mortality from infections by comparing the underlying causes of death versus the multiple causes of death in known diabetic subjects living in the Veneto region of Northern Italy. METHODS AND RESULTS: A total of 185,341 subjects with diabetes aged 30-89 years were identified in the year 2010, and causes of death were assessed from 2010 to 2015. Standardized Mortality Ratios (SMRs) with 95% confidence intervals (CIs) were computed with regional mortality rates as reference. The underlying causes of death and all the diseases reported in the death certificates were scrutinized. At the end of the follow-up, 36,382 subjects had deceased. We observed an increased risk of death from infection-related causes in subjects with diabetes with a SMR of 1.83 (95% CI, 1.71-1.94). The SMR for death from septicemia was 1.91 (95% CI, 1.76-2.06) and from pneumonia was 1.47 (95% CI, 1.36-1.59). The use of the multiple causes of death approach emphasized the association of infectious diseases with mortality. CONCLUSION: The results of the present study demonstrate an excess mortality due to infection-related diseases in patients with diabetes; more interestingly, by routine mortality analyses, the results show a possible underestimation of the effect of these diseases on mortality.

Sífilis secundaria con lesiones de la cavidad bucal como única manifestación clínica Presentación de 20 casos y revisión de la literatura / SECONDARY SYPHILIS WITH BUCAL CAVITY LESIONS AS SINGLE CLINICAL MANIFESTATION

La sífilis es una enfermedad infectocontagiosa causada por una espiroqueta: el Treponema pallidum. Se transmite por contacto directo (generalmente sexual) con las lesiones cutáneo-mucosas durante el estadio primario y secundario, por vía transplacentaria durante el embarazo o a través del pasaje por el canal uterino y por sangre. Se trata de una enfermedad sistémica con una gran variedad de manifestaciones clínicas. La sífilis secundaria cursa con manifestaciones generales de un síndrome infeccioso inespecífico y lesiones mucocutáneas características. La presentación clínica de los 20 pacientes que se describen en este trabajo es singular ya que solo poseían lesiones en la cavidad oral. Es importante considerar esta patología en el diagnóstico diferencial de lesiones mucosas orales, para realizar un diagnóstico temprano, tratamiento precoz y evitar el contagio, así como siempre descartar la asociación con infección por el retrovirus VIH

Syphilis is a sexually transmitted disease caused by the spirochete bacterium named as Treponema pallidum. Syphilis is transmitted by direct contact (generally non-protect sexual contact) with cutaneous and mucosal lesions during the primary and secondary periods, by trans-placental transmission if the mother develop the infection during pregnancy and by blood. Syphilis is a systemic disease with a wide variety of clinical manifestations. Secondary syphilis is characterized by a nonspecific infectious syndrome and mucocutaneous lesions. Here we describe a serie of 20 patients with secondary syphilis as the unique clinical manifestation. Secondary syphilis should be included in the differential diagnosis of oral cavity mucosal lesions to achieve an early diagnosis and avoid the contagion. Human immunodeficiency virus infection should be always considered

Survival and recurrent venous thromboembolism in patients with first proximal or isolated distal deep vein thrombosis and no pulmonary embolism.

Essentials The long-term risk of recurrence and death after distal deep vein thrombosis (DVT) is uncertain. We included subjects with first proximal or isolated distal DVT (IDDVT) and no pulmonary embolism. The risk of symptomatic and asymptomatic recurrence is lower after IDDVT (vs. proximal). IDDVT may be associated with a lower long-term risk of death, especially after unprovoked DVT. SUMMARY: Background A few studies have focused on the risk of recurrence after first acute isolated distal deep vein thrombosis (IDDVT) compared with proximal DVT (PDVT), whereas the incremental risk of death has never been explored beyond the first 3 years after acute event. Methods Our single-center cohort study included patients with first symptomatic acute PDVT or IDDVT. Patients were excluded if they had concomitant pulmonary embolism (PE) or prior venous thromboembolism. The primary outcomes were symptomatic objectively diagnosed recurrent PDVT or PE and all-cause death. Results In total, 4759 records were screened and 831 subjects included: 202 had symptomatic IDDVT and 629 had PDVT. The median age was 66 years and 50.5% were women. A total of 125 patients had recurrent PDVT or PE during 3175 patient-years of follow-up: 109 events occurred after PDVT (17.3%) and 16 after IDDVT (7.9%). Annual recurrence rates were 4.5% (95% confidence interval [CI], 3.7-5.4%) and 2.0% (95% CI, 1.1-3.2%), respectively, for an adjusted hazard ratio (aHR) for IDDVT patients of 0.32 (95% CI, 0.19-0.55). Death occurred in 263 patients (31.6% [95% CI, 28.6-34.9%]) during 5469 patient-years of follow-up for an overall annual incidence rate of 4.8% (95% CI, 4.2-5.4%). The mortality rate was 33.5% (n = 211) in PDVT patients and 25.7% (n = 52) in IDDVT patients. The long-term hazard of death appeared lower for IDDVT patients (aHR, 0.75 [95% CI, 0.55-1.02]), especially after unprovoked events (aHR, 0.58 [95% CI, 0.26-1.31]). Conclusions Compared with PDVT, IDDVT patients were at a lower risk of recurrent VTE. The risk of death appeared lower after IDDVT during a median follow-up of 7.6 years.

Water response to ganglioside GM1 surface remodelling.

BACKGROUND: Gangliosides are biological glycolipids participating in rafts, structural and functional domains of cell membranes. Their headgroups are able to assume different conformations when packed on the surface of an aggregate, more lying or standing. Switching between different conformations is possible, and is a collective event. Switching can be induced, in model systems, by concentration or temperature increase, then possibly involving ganglioside-water interaction. In the present paper, the effect of GM1 ganglioside headgroup conformation on the water structuring and interactions is addressed. METHODS: Depolarized Rayleigh Scattering, Raman Scattering, Quasielastic Neutron Scattering and NMR measurements were performed on GM1 ganglioside solutions, focusing on solvent properties. RESULTS: All used techniques agree in evidencing differences in the structure and dynamics of solvent water on different time-and-length scales in the presence of either GM1 headgroup conformations. CONCLUSIONS: In general, all results indicate that both the structural properties of solvent water and its interactions with the sugar headgroups of GM1 respond to surface remodelling. The extent of this modification is much higher than expected and, interestingly, ganglioside headgroups seem to turn from cosmotropes to chaotropes upon collective rearrangement from the standing- to the lying-conformation. SIGNIFICANCE: In a biological perspective, water structure modulation could be one of the physico-chemical elements contributing to the raft strategy, both for rafts formation and persistence and for their functional aspects. In particular, the interaction with approaching bodies could be favoured or inhibited or triggered by complex-sugar-sequence conformational switch. This article is part of a Special Issue entitled "Science for Life" Guest Editor: Dr. Austen Angell, Dr. Salvatore Magazù and Dr. Federica Migliardo.

A majority rule approach for region-of-interest-guided streamline fiber tractography.

Hand-drawn gray matter regions of interest (ROI) are often used to guide the estimation of white matter tractography, obtained from diffusion-weighted magnetic resonance imaging (DWI), in healthy and in patient populations. However, such ROIs are vulnerable to rater bias of the individual segmenting the ROIs, scan variability, and individual differences in neuroanatomy. In this report, a "majority rule" approach is introduced for ROI segmentation used to guide streamline tractography in white matter structures. DWI of one healthy participant was acquired in ten separate sessions using a 3 T scanner over the course of a month. Four raters identified ROIs within the left hemisphere [Cerebral Peduncle (CPED); Internal Capsule (IC); Hand Portion of the Motor Cortex, or Hand Bump, (HB)] using a group-established standard operating procedure for ROI definition to guide the estimation of streamline tracts within the corticospinal tract (CST). Each rater traced the ROIs twice for each scan session. The overlap of each rater's two ROIs was used to define a representative ROI for each rater. These ROIs were combined to create a "majority rules" ROI, in which the rule requires that each voxel is selected by at least three of four raters. Reproducibility for ROIs and CST segmentations were analyzed with the Dice Similarity Coefficient (DSC). Intra-rater reliability for each ROI was high (DSCs ≥ 0.83). Inter-rater reliability was moderate to adequate (DSC range 0.54-0.75; lowest for IC). Using intersected majority rules ROIs, the resulting CST showed improved overlap (DSC = 0.82) in the estimated streamline tracks for the ten sessions. Despite high intra-rater reliability, there was lower inter-rater reliability consistent with the expectation of rater bias. Employing the majority rules method improved reliability in the overlap of the CST.

Characterization of magnetic nanoparticles from Magnetospirillum Gryphiswaldense as potential theranostics tools.

We investigated the theranostic properties of magnetosomes (MNs) extracted from magnetotactic bacteria, promising for nanomedicine applications. Besides a physico-chemical characterization, their potentiality as mediators for magnetic fluid hyperthermia and contrast agents for magnetic resonance imaging, both in vitro and in vivo, are here singled out. The MNs, constituted by magnetite nanocrystals arranged in chains, show a superparamagnetic behaviour and a clear evidence of Verwey transition, as signature of magnetite presence. The phospholipid membrane provides a good protection against oxidation and the MNs oxidation state is stable over months. Using an alternate magnetic field, the specific absorption rate was measured, resulting among the highest reported in literature. The MRI contrast efficiency was evaluated by means of the acquisition of complete NMRD profiles. The transverse relaxivity resulted as high as the one of a former commercial contrast agent. The MNs were inoculated into an animal model of tumour and their presence was detected by magnetic resonance images two weeks after the injection in the tumour mass.

Obesity, Muscular Strength, Muscle Composition and Physical Performance in an Elderly Population.

OBJECTIVE: To evaluate the association between BMI levels, muscular strength, muscle composition and physical performance in the elderly. DESIGN: Italians subjects from the Progetto Veneto Anziani (ProVA) study were analyzed. SETTING: The ProVa was a population study focused on chronic diseases and functional limitations in Italian subjects aged ≥65 years living in two Northeast Italian cities. PARTICIPANTS: The ProVa study included 3099 subjects. ProVa participants with unknown information on BMI or disability status were excluded. The final sample was thus represented by 1.188 men, and 1.723 women. MEASUREMENTS: Physical performance was measured with the Short Physical Performance Battery (SPPB) and leg muscular strength with dynamometry. Fat distribution and skeletal muscle composition were measured in an abdominal single-scan magnetic resonance (MRI) in a randomly selected sample of 348 subjects. Study population was stratified by BMI classes. RESULTS: An association between BMI levels and SPPB was observed. Normal weight subjects showed the best SPPB scores (8.29±0.03), with significant differences compared to underweight (7.50±0.15; p<0.001), overweight (8.12±0.02; p<0.001), class I (7.72±0.04; p<0.001), class II (6.67±0.09; p<0.001) and class III obesity (5.88±0.24; p<0.001). This pattern was not modified by adjustment for possible confounders. Compared to normal weight subjects (22.9±0.1 kg), leg muscular strength was higher in overweight (23.8±0.1; p<0.001) and in class I obesity (24.5±0.1; p<0.001), but it was reduced in class II (21.4±0.3; p<0.001) and class III (19.8±0.9; p<0.001). The association between BMI and impaired physical performance was not affected by adjustment for muscular strength. An inverse association between SPPB scores and fat infiltration in skeletal muscle was observed in patients with abdominal MRI. CONCLUSION: A poor physical performance was observed in overweight and obese elderly subjects. Leg strength was reduced only in subjects with severe obesity. Physical performance was negatively influenced by the degree of fat infiltration in skeletal muscle.

Hepatitis C virus long-term persistence in peripheral blood mononuclear cells in patients with haemophilia. Detection of occult genotype 1.

Peripheral blood mononuclear cells (PBMC) from chronic hepatitis C virus-infected persons can harbour viral variants that are not detected in plasma samples. We explored the presence and persistence of HCV genotypes in plasma and PBMC cultures from 25 HCV-monoinfected and 25 HIV/HCV-coinfected patients with haemophilia. Cell cultures were performed at different time points between 1993 and 2010-2011, and the HCV genome was examined in culture supernatants. Sequential plasma samples were studied during the same time period. Analysing sequential plasma samples, 21% of patients had mixed-genotype infections, while 50% had mixed infections determined from PBMC culture supernatants. HIV coinfection was significantly associated with the presence of mixed infections (OR = 4.57, P = 0.02; 95% CI = 1.38-15.1). In our previous study, genotype 1 was found in 72% of 288 patients of this cohort. Similar results were obtained with the sequential plasma samples included in this study, 69% had genotype 1. However, when taking into account plasma samples and the results from PBMC supernatants, genotype 1 was identified in 94% of the population. The PBMC-associated variants persisted for 10 years in some subjects, emphasizing their role as long-term reservoirs. The presence of genotype 1 in PBMC may be associated with therapeutic failure and should not be disregarded when treating haemophilic patients who have been infected by contaminated factor concentrates. The clinical implications of persistent lymphotropic HCV variants deserve further examination among multiple exposed groups of HCV-infected patients.

ALERGIA A LA PROTEíNA DE LA LECHE DE VACA. EVALUACIóN DE SU RESOLUCIóN ESPONTáNEA POR MEDIO DE DESAFíOS DOBLE CIEGO PLACEBO CONTROLADOS / cows milk allergy. an assesment of its spontaneous resolution through double blind placebo controlled challenges.

Introducción. la alergia a la leche de vaca (aplv) es un problema sanitario global. Su diagnóstico adecuado y su seguimiento son esenciales ya que la leche de vaca es un alimento importante en la dieta de muchos lactantes. los desafíos orales doble ciego controlados por placebo (ddcpc) son la herramienta ideal para el diagnóstico y seguimiento de las alergias alimentarias. este estudio describe las características evolutivas de pacientes con aplv y las posibles variables que la pudieran modificar. material y métodos. Se estudiaron pacientes con diagnóstico de aplv previo con desafíos abiertos. Se catalogaron las reacciones de acuerdo a la normativa dracma. positivas fueron las pruebas en las que se presentaron alteraciones clínicas o variaciones hemodinámicas. negativas fueron aquellas en las que el paciente toleró la leche. Se consideraron edades de inicio y de realización del ddcpc, sexo y patología de aplv. resultados. Se estudiaron 106 pacientes (50 masculinos, 56 femeninos), promedio edad de inicio de síntomas 5,31 m (rango: 1-48 meses) y al procedimiento 23,14 m (5 meses - 5 años), y 13 pruebas positivas. un conjunto se refirió al mecanismo fisiopatológico y se dividió en ige mediadas (n=55) con 8 pruebas positivas y mixtas/celulares (n=51) con 5 pruebas positivas. otro conjunto fueron no gastrointestinales (n=61) con 7 pruebas positivas y gastrointestinales (n=45) con 6 pruebas positivas. todos los grupos fueron similares en cuanto a las variables demográficas. el sexo masculino y el diagnóstico de anafilaxia fueron factores de riesgo para no resolver su aplv (p=0,0125 y p=0,002 respectivamente). conclusiones. el momento de resolución de la aplv es independiente del mecanismo fisiopatológico subyacente o la edad de inicio de los síntomas. en general resuelven el problema de manera espontánea hacia los dos años de vida en más de un 87% de los casos. el sexo masculino (en ige mediadas) y el antecedente de anafilaxia podrían ser factores de riesgo para tener menos probabilidades de resolver la APLV. (AU)

Introduction: cow´s milk allergy (cma) is a global health issue. a proper diagnosis and follow up become essential. double blind placebo controlled challenges (dbpcc) is the gold standard for this purpose. this paper describes clinical evolution and characteristics of cma, as well as variables that may modify the affection course. methods & material: a group of patients, with a previous diagnosis of cma by open challenges, has been studied and its results cataloged according to dracma guidelines. tests with hemodynamic changes or clinical symptoms were considered as positives, while those with no clinical reaction were considered as negatives. variables involved were: age of symptoms starting, age of dbpcc performing, gender and cma clinical manifestations. results: 106 patients has been studied (50 male, 56 female), with a median age of 5,31 mo (range 5 ­ 48 mo) at the starting symptoms, and a median age of 23,14 mo (range 5 mo ­ 5 y) at the performing of dbpcc. 13 tests were negative. as regards to the different immune mechanisms, 55 were ige dependent (8 negative), and 51 were mediated by mixed/cellular (5 negative). patients were divided into two groups: with gastrointestinal symptoms (n=45) and with no gastrointestinal symptoms (n=61). they showed 6 and 7 negative results, respectively. all groups were similar. male gender, and anaphylaxis diagnosis turned out to be risk factors not to resolve cma (p=0,0125 and p=0,002 respectively). conclusions: cma resolution is independent of the immune mechanisms involved or the age of its symptoms starting. cma is solved spontaneously towards the age of two in 87% of the cases. male gender, and anaphylaxis may become risk factors not to resolve cma.(AU)