High incidence of severe cyclosporine neurotoxicity in children affected by haemoglobinopaties undergoing myeloablative haematopoietic stem cell transplantation: early diagnosis and prompt intervention ameliorates neurological outcome

<p>Abstract</p> <p>Background</p> <p>Neurotoxicity is a recognized complication of cyclosporine A (CSA) treatment. The incidence of severe CSA-related neurological complications following hematopoietic stem cell transplantation (HSCT) is 4-11%.</p> <p>Methods</p> <p>We describe 6 cases of CSA related neurotoxicity out of 67 matched related HSCT performed in paediatric Middle East patients affected by haemoglobinopaties (5 beta thalassemia major, 1 sickle cell disease-SCD). Conditioning regimen consisted of iv busulphan, cyclophosphamide and graft-versus-host-disease (GvHD) prophylaxis with CSA, methylprednisolone, methotrexate and ATG.</p> <p>Results</p> <p>All 6 patients presented prodromes such as arterial hypertension, headache, visual disturbances and vomiting, one to two days before overt CSA neurotoxicity. CSA neurotoxicity consisted of generalized seizures, signs of endocranial hypertension and visual disturbances at a median day of onset of 11 days after HSCT (range +1 to +40). Brain magnetic resonance imaging (MRI) performed in all subjects showed reversible leukoencephalopathy predominantly in the posterior regions of the brain (PRES) in 5/6 patients. EEG performed in 5/6 patients was always abnormal. Neurotoxicity was not explainable by high CSA blood levels, as all patients had CSA in the therapeutic range with a median of 178 ng/ml (range 69-250). CSA was promptly stopped and switched to tacrolimus with disappearance of clinical and radiological findings. All patients are symptoms-free at a median follow up of 882 days (range 60-1065).</p> <p>Conclusions</p> <p>Our experience suggests that paediatric patients with haemoglobinopaties have a high incidence of CSA related neurological events with no correlation between serum CSA levels and neurotoxicity. Prognosis is good following CSA removal. Specific prodromes such as arterial hypertension, headache or visual disturbances occurring in the early post-transplant period should be carefully evaluated with electrophysiological and MRI-based imaging in order to intervene promptly and avoid irreversible sequels.</p

A Survey on the milk fatty acid composition of forty dairy sheep flocks in Sardinia

A survey was carried out to monitor milk fatty acid (FA) composition during two years (2003 and 2004) on forty dairy sheep flocks, fed pasture based rations, in 5 macro pedoclimatic areas of Sardinia, featured by different i) soil type, (granitic, G; basaltic, B and alluvial, A) ii) average annual rainfall (low, L, 500-600 mm/year; high, H, 600-800 mm/year). Milk FA profile was strongly influenced by year. In particular milk linolenic acid (LN), CLA (conjugated linoeic acid) and PUFA (polyunsaturated fatty acids) levels increased (by 25, 30 and 14%, respectively, P&lt;0.01) whereas the atherogenicity index (AI) decreased (by 8%, P&lt;0.01) in all areas in 2004 as compared with 2003. Pedoclimatic area affected milk fatty acid composition (P&lt;0.01). In both years milk from AL farms showed the highest levels of LN, CLA and PUFA. AI was lower in BH and GH in year 2003 and in BH, AH and GL in 2004

Luigi Pirandello: um teatro para Marta Abba

Em dezembro de 2016 foi publicada a lei nº 13.409 que dispôs sobre a reserva de vagas para pessoas com deficiência nos cursos superiores e técnicos de nível médio das instituições federais de ensino (Ifes). Desde então, as Ifes têm enfrentado o desafio de incluir em seus espaços escolares alunos com diversas necessidades educacionais específicas. Este artigo teve por objetivo investigar a inclusão de alunos surdos sob a perspectiva de professores de um curso técnico de nível médio integrado do Instituto Federal de Educação, Ciência e Tecnologia de Alagoas (Ifal). Para tanto, foi utilizada a metodologia qualitativa, com base na pesquisa-ação, por meio da aplicação de um questionário semiestruturado. Os resultados apontaram lacunas no processo de inclusão de alunos surdos, como a carência de profissionais tradutores e intérpretes de Libras, a falta de conhecimento sobre a Cultura Surda no planejamento pedagógico e a necessidade de formação continuada para os professores voltada à inclusão escolar. Por fim, os professores também indicaram possíveis ações para minimizar tais dificuldades, de forma que a prática docente se revista, de fato, dos princípios que integram a Educação Inclusiva.In December 2016, Law No. 13,409 was published, which provided for the reservation of vacancies for people with disabilities in higher education and high school technical courses at federal educational institutions (Ifes). Since then, Ifes have faced the challenge of including students with different specific educational needs in their school spaces. This article intends to investigate the inclusion of deaf students according to teacher’s perspective from an integrated high school technical course at the Federal Institute of Education, Science and Technology of Alagoas (Ifal). Therefore, the qualitative methodology was used, based on action research, through the application of a semi-structured questionnaire. The results pointed out blanks in the inclusion process for deaf students, such as the lack of professional translators and interpreters of Libras, the lack of knowledge about Deaf Culture in pedagogical planning and the need for continuing education for teachers focused on school inclusion. Finally, teachers also indicated possible actions to minimize such difficulties, so that teaching practice is, in fact, based on the principles that make up Inclusive Education.En diciembre de 2016 se publicó la Ley N ° 13.409, que dispuso la reserva de vacantes para personas con discapacidad en los cursos técnicos de educación superior y bachillerato en las instituciones educativas federales (Ifes). Desde entonces, Ifes se ha enfrentado al desafío de incluir a estudiantes con diferentes necesidades educativas específicas en sus espacios escolares. Este artículo tuvo como objetivo investigar la inclusión de estudiantes sordos desde la perspectiva de los docentes de un curso técnico integrado de bachillerato en el Instituto Federal de Educación, Ciencia y Tecnología de Alagoas (Ifal). Para ello se utilizó la metodología cualitativa, basada en la investigación acción, mediante la aplicación de un cuestionario semiestructurado. Los resultados evidenciaron brechas en el proceso de inclusión de estudiantes sordos, como la falta de traductores e intérpretes profesionales de Libras, el desconocimiento de la cultura de las personas sordas en la planificación pedagógica y la necesidad de una formación continua para los docentes enfocada en la inclusión escolar. Finalmente, los docentes también señalaron posibles acciones para minimizar tales dificultades, de manera que la práctica docente se base, de hecho, en los principios que componen la Educación Integrada

Extensive genetic diversity, unique population structure and evidence of genetic exchange in the sexually transmitted parasite <i>Trichomonas vaginalis</i>

Background Trichomonas vaginalis is the causative agent of human trichomoniasis, the most common non-viral sexually transmitted infection world-wide. Despite its prevalence, little is known about the genetic diversity and population structure of this haploid parasite due to the lack of appropriate tools. The development of a panel of microsatellite makers and SNPs from mining the parasite's genome sequence has paved the way to a global analysis of the genetic structure of the pathogen and association with clinical phenotypes. Methodology/Principal Findings Here we utilize a panel of T. vaginalis-specific genetic markers to genotype 235 isolates from Mexico, Chile, India, Australia, Papua New Guinea, Italy, Africa and the United States, including 19 clinical isolates recently collected from 270 women attending New York City sexually transmitted disease clinics. Using population genetic analysis, we show that T. vaginalis is a genetically diverse parasite with a unique population structure consisting of two types present in equal proportions world-wide. Parasites belonging to the two types (type 1 and type 2) differ significantly in the rate at which they harbor the T. vaginalis virus, a dsRNA virus implicated in parasite pathogenesis, and in their sensitivity to the widely-used drug, metronidazole. We also uncover evidence of genetic exchange, indicating a sexual life-cycle of the parasite despite an absence of morphologically-distinct sexual stages. Conclusions/Significance Our study represents the first robust and comprehensive evaluation of global T. vaginalis genetic diversity and population structure. Our identification of a unique two-type structure, and the clinically relevant phenotypes associated with them, provides a new dimension for understanding T. vaginalis pathogenesis. In addition, our demonstration of the possibility of genetic exchange in the parasite has important implications for genetic research and control of the disease

Extensive Genetic Diversity, Unique Population Structure and Evidence of Genetic Exchange in the Sexually Transmitted Parasite Trichomonas vaginalis

The human parasite Trichomonas vaginalis causes trichomoniasis, the world's most common non-viral sexually transmitted infection. Research on T. vaginalis genetic diversity has been limited by a lack of appropriate genotyping tools. To address this problem, we recently published a panel of T. vaginalis-specific genetic markers; here we use these markers to genotype isolates collected from ten regions around the globe. We detect high levels of genetic diversity, infer a two-type population structure, identify clinically relevant differences between the two types, and uncover evidence of genetic exchange in what was believed to be a clonal organism. Together, these results greatly improve our understanding of the population genetics of T. vaginalis and provide insights into the possibility of genetic exchange in the parasite, with implications for the epidemiology and control of the disease. By taking into account the existence of different types and their unique characteristics, we can improve understanding of the wide range of symptoms that patients manifest and better implement appropriate drug treatment. In addition, by recognizing the possibility of genetic exchange, we are more equipped to address the growing concern of drug resistance and the mechanisms by which it may spread within parasite populations

Clinical Features, Cardiovascular Risk Profile, and Therapeutic Trajectories of Patients with Type 2 Diabetes Candidate for Oral Semaglutide Therapy in the Italian Specialist Care

Introduction: This study aimed to address therapeutic inertia in the management of type 2 diabetes (T2D) by investigating the potential of early treatment with oral semaglutide. Methods: A cross-sectional survey was conducted between October 2021 and April 2022 among specialists treating individuals with T2D. A scientific committee designed a data collection form covering demographics, cardiovascular risk, glucose control metrics, ongoing therapies, and physician judgments on treatment appropriateness. Participants completed anonymous patient questionnaires reflecting routine clinical encounters. The preferred therapeutic regimen for each patient was also identified. Results: The analysis was conducted on 4449 patients initiating oral semaglutide. The population had a relatively short disease duration (42%  60% of patients, and more often than sitagliptin or empagliflozin. Conclusion: The study supports the potential of early implementation of oral semaglutide as a strategy to overcome therapeutic inertia and enhance T2D management

The eneolithic site of Cava Gazzuoli (Modena): an early stage of the Spilamberto group

This paper combines the documentation work of the Eneolithic stratigraphic and structural evidence of the site of Cava Gazzuoli, carried out by SAP archaeological company, and the master's thesis work of F. Barchiesi who subsequently studied the materials. In particular, the study refers to an extensive quarry complex located in the municipality of Modena, on the border with the municipality of Formigine (Emilia-Romagna, northern Italy). After the analysis of the pottery and lithic industry, we suggest that the site (most likely a settlement) belongs to an early phase of the Spilamberto Group (middle 4th-middle 3rd millennium BC), with clear references to the late Neolithic facies of Sant’Ilario

Sedative effect of acupuncture during cataract surgery: prospective randomized double-blind study

To assess the effectiveness of acupuncture in reducing anxiety in patients having cataract surgery under topical anesthesia

Comparative analysis of clinical features and prognostic factors in resected bronchioloalveolar carcinoma and adenocarcinoma of the lung

Background: Over the past few years, clinical, radiological and pathological classification of lung adenocarcinoma and its subtypes, particularly bronchioloalveolar carcinoma (BAC), has radically changed. Patients and Methods: Out of a series of 384 non-small cell lung cancer (NSCLC) patients, submitted to surgical resection and followed-up in our Department from 1981 to 1999, the data of 151 adenocarcinomas (35 BAC and 116 non-BAC) were reviewed and analyzed for prognosis. Results: BAC and non-BAC series were similar in clinical and radiographic findings, type of resection and stage. Stage I was a dominant favorable prognostic factor (10-year survival: 58% of BAC, 41.2% of non-BAC), albeit associated with a significant risk of second primary metachronous lung tumor (10-year risk: 25% of BAC, 32% of non-BAC). Other independent prognostic factors were: absence of lymph node involvement for BAC and stage III-IVfor non-BAC. In term of prognosis, advantages of BAC over non-BAC were fewer cases with lymph node involvement, increased presence of "well-differentiated" cells (p = 0.016) and lower incidence of a second primary metachronous tumor. Moreover BAC patients with a single nodule or mass also had a higher survival expectancy (mean survival: 77 months versus 56 for non-BAC). An unfavorable feature was the higher incidence of diffuse or multicentric radiological forms (p=0.012). For both groups the presence of multiple or satellite nodules remain a diagnostic and surgical challenge: in BAC cases the evaluation of clonality is recommended

Metabolic Bile Acid Profile Impairments in Dogs Affected by Chronic Inflammatory Enteropathy

Bile acids (BAs), endogenous acidic steroids synthetized from cholesterol in the liver, play a key role in the gut–liver axis physiopathology, including in hepatotoxicity, intestinal inflammatory processes, and cholesterol homeostasis. Faecal Oxo-BAs, relatively stable intermediates of oxidation/epimerization reactions of the BA hydroxyls, could be relevant to investigating the crosstalk in the liver–gut axis and the relationship between diseases and alterations in microbiota composition. A paucity of information currently exists on faecal BA profiles in dogs with and without chronic inflammatory enteropathy (CIE). Comprehensive assessment of 31 molecules among faecal BAs and related microbiota metabolites was conducted with high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS). Odds ratios (ORs) for associations of BAs with CIE were estimated using logistic regression. Principal component analysis was performed to find differences between the control and pathological dogs. Higher levels of primary BAs and muricholic acids, and lower levels of secondary BAs were found in pathological dogs. Higher concentrations in faecal oxo-metabolites were associated with the absence of CIE (OR < 1). This study shows a marked difference in faecal BA profiles between dogs with and without CIE. Further research will be needed to better understand the role of oxo-BAs and muricholic acids in CIE dogs