Normative growth charts for Shwachman-Diamond syndrome from Italian cohort of 0-8 years old

Shwachman-Diamond syndrome (SDS) is a rare autosomal recessive disorder. Its predominant manifestations include exocrine pancreatic insufficiency, bone marrow failure and skeletal abnormalities. Patients frequently present failure to thrive and susceptibility to short stature. Average birth weight is at the 25th percentile; by the first birthday, >50% of patients drop below the third percentile for height and weight.The study aims at estimating the growth charts for patients affected by SDS in order to give a reference tool helpful for medical care and growth surveillance through the first 8 years of patient's life

Diffuse alterations in grey and white matter associated with cognitive impairment in Shwachman–Diamond syndrome: Evidence from a multimodal approach

Shwachman–Diamond syndrome is a rare recessive genetic disease caused by mutations in SBDS gene, at chromosome 7q11. Phenotypically, the syndrome is characterized by exocrine pancreatic insufficiency, bone marrow dysfunction, skeletal dysplasia and variable cognitive impairments. Structural brain abnormalities (smaller head circumference and decreased brain volume) have also been reported. No correlation studies between brain abnormalities and neuropsychological features have yet been performed. In this study we investigate neuroanatomical findings, neurofunctional pathways and cognitive functioning of Shwachman–Diamond syndrome subjects compared with healthy controls. To be eligible for inclusion, participants were required to have known SBDS mutations on both alleles, no history of cranial trauma or any standard contraindication to magnetic resonance imaging. Appropriate tests were used to assess cognitive functions. The static images were acquired on a 3 × 0 T magnetic resonance scanner and blood oxygen level-dependent functional magnetic resonance imaging data were collected both during the execution of the Stroop task and at rest. Diffusion tensor imaging was used to assess brain white matter. The Tract-based Spatial Statistics package and probabilistic tractography were used to characterize white matter pathways. Nine participants (5 males), half of all the subjects aged 9–19 years included in the Italian Shwachman–Diamond Syndrome Registry, were evaluated and compared with nine healthy subjects, matched for sex and age. The patients performed less well than norms and controls on cognitive tasks (p = 0.0002). Overall, cortical thickness was greater in the patients, both in the left (+10%) and in the right (+15%) hemisphere, significantly differently increased in the temporal (left and right, p = 0.04), and right parietal (p = 0.03) lobes and in Brodmann area 44 (p = 0.04) of the right frontal lobe. The greatest increases were observed in the left limbic-anterior cingulate cortex (≥43%, p < 0.0004). Only in Broca's area in the left hemisphere did the patients show a thinner cortical thickness than that of controls (p = 0.01). Diffusion tensor imaging showed large, significant difference increases in both fractional anisotropy (+37%, p < 0.0001) and mean diffusivity (+35%, p < 0.005); the Tract-based Spatial Statistics analysis identified six abnormal clusters of white matter fibres in the fronto-callosal, right fronto-external capsulae, left fronto-parietal, right pontine, temporo-mesial and left anterior–medial–temporal regions. Brain areas activated during the Stroop task and those active during the resting state, are different, fewer and smaller in patients and correlate with worse performance (p = 0.002). Cognitive impairment in Shwachman–Diamond syndrome subjects is associated with diffuse brain anomalies in the grey matter (verbal skills with BA44 and BA20 in the right hemisphere; perceptual skills with BA5, 37, 20, 21, 42 in the left hemisphere) and white matter connectivity (verbal skills with alterations in the fronto-occipital fasciculus and with the inferior-longitudinal fasciculus; perceptual skills with the arcuate fasciculus, limbic and ponto-cerebellar fasciculus; memory skills with the arcuate fasciculus; executive functions with the anterior cingulated and arcuate fasciculus)

GENETIC ANALYSIS OF THE SBDS GENE AMONG NON-ITALIAN PATIENTS

The SBDS mRNA is widely expressed in many tissues and its mutations cause a wide variety of abnormalities and symptoms, so the diagnosis is not always immediately obvious. The screening for mutations in the SBDS gene started, in our laboratory, in 2003. In a period of 13 years we analyzed, after obtained informed consent, a total of 174 families having one suspected SDS patient. Part of the 174 families were of non-Italian origin: these samples arrived to our laboratory by direct communications from family doctors or by the Genetic Testing Registry (GTR\uae). GTR provides a central location for voluntary submission of genetic test information by providers. As providers of: confirmation of research findings, sequence analysis, genetic counseling, prenatal testing, mutation-specific/carrier testing, we analyzed a total of 28 families from the following nationalities: Australia, Bangladesh, China, Egypt, India, Latvia, Lebanon, Libya, Morocco, Pakistan, Philippines, Romania, Santo Domingo,Turkey, Ukraine, Vietnam. Among the 25 families, we characterized, as SDS, 8 patients. The median (range)\ua0age at diagnosis\ua0was 2.8 (0.1-7) years. The clinical status at diagnosis appears very similar between Italian and non-Italian patients. Pancreatic dysfunctions is present in the majority of subjects as well as hematologic abnormalities and infections. The SDS alleles reflect the frequencies observed in Italy. Two mutations are not present in the Italian SDS patients: the missense mutation c.523C>T in exon 4, found in homozygosis and the c.307_308delCA, a frame shift deletion in the exon 3 leading to a premature stop codon. The SDS is described in even more geographic area of the world among different ethnic population

A Prospective Study of Hematologic Complications and Long-Term Survival of Italian Patients Affected by Shwachman-Diamond Syndrome

To describe the hematologic outcome and long-term survival of patients enrolled in the Shwachman-Diamond syndrome Italian Registry

Covid-19: consecuencias y desafíos en la economía colombiana. Una mirada desde las universidades

Este libro reúne diferentes hallazgos, perspectivas y efectos ante un fenómeno que, más de un año después, todavía representa un reto científico, médico y social para todos. Igualmente, esta obra representa el objetivo de la Red Investigadores de Economía: aunar esfuerzos para encontrar respuestas y para fortalecer la investigación en el país, aumentar la difusión de trabajos de calidad y propiciar el encuentro entre académicos, universidades y el Banco de la República. Las investigaciones expuestas en este libro pasaron por un proceso de selección por parte del comité científico, asegurando que hubiese una pluralidad de miradas y de instituciones educativas, además del Banco, donde se relacionaran los efectos de la pandemia y la actividad económica en el país, las consecuencias sociales y regionales. El texto está dividido en cuatro partes. En la primera se hace un análisis macroeconómico de los efectos de la pandemia; para ello se examinan los efectos de la emergencia sanitaria a nivel nacional y regional mediante modelos macroeconómicos que permiten obtener respuestas ante preguntas muy relevantes. La segunda sección trata sobre el impacto en el mercado laboral, el efecto del Covid-19 en la distribución del ingreso y el efecto de corto plazo en el mercado urbano. La tercera parte aborda los efectos de la pandemia en los agentes económicos y en otros mercados. Ello incluye la exposición del empleo al Covid-19, la vulnerabilidad económica de los hogares en el país y su respuesta en el consumo, patrones de actividad laboral y salud mental, efectos en la educación, inseguridad alimentaria de la población migrante, entre otros. Por último, el cuarto segmento hace un énfasis especial en los efectos diferenciales entre las regiones del país y la heterogeneidad de dicho impacto; para ello se analizan temas de informalidad, vulnerabilidad, fuerza de trabajo disponible, entre otros, en distintas regiones del país