The New Modular Sforzesco Brace (Modular Italian Brace) Is as Effective as the Classical One: A Retrospective Controlled Study from a Prospective Cohort.

: The Sforzesco brace is a very rigid push-up brace effective in adolescent idiopathic scoliosis (AIS). We recently developed a new Sforzesco brace based on modularity (the Modular Italian brace-MI brace) that could allow standardization, facilitating global expertise diffusion, increased modifiability and adaptability, and cost savings due to longer brace life. We aimed to compare the short-term results of the two braces.

The Usefulness of a Targeted Next Generation Sequencing Gene Panel in Providing Molecular Diagnosis to Patients With a Broad Spectrum of Neurodevelopmental Disorders.

Neurodevelopmental disorders comprise a clinically and genetically heterogeneous group of conditions that affect 2%-5% of children and represents a public health challenge due to complexity of the etiology. Only few patients with unexplained syndromic and non-syndromic NDDs receive a diagnosis through first-tier genetic tests as array-CGH and the search for CGG expansion. The aim of this study was to evaluate the clinical performance of a targeted next-generation sequencing (NGS) gene panel as a second-tier test in a group of undiagnosed patients with NDDs.

Next-Generation Sequencing Advances the Genetic Diagnosis of Cerebral Cavernous Malformation (CCM).

Cerebral Cavernous Malformation (CCM) is a cerebrovascular disease of genetic origin that predisposes to seizures, focal neurological deficits and fatal intracerebral hemorrhage. It may occur sporadically or in familial forms, segregating as an autosomal dominant condition with incomplete penetrance and highly variable expressivity. Its pathogenesis has been associated with loss-of-function mutations in three genes, namely KRIT1 (CCM1), CCM2 and PDCD10 (CCM3), which are implicated in defense mechanisms against oxidative stress and inflammation.

Impact of the Free-Pelvis Innovation in Very Rigid Braces for Adolescents with Idiopathic Scoliosis: Short-Term Results of a Matched Case-Control Study.

We introduced pelvis semi-rigid material (ethylene vinyl acetate) (Free-Pelvis) to improve the comfort and adaptability of very rigid braces (VRBs) for adolescents with idiopathic scoliosis (AIS), but this can also negatively impact the corrective forces on the trunk. Study Design: This was a matched retrospective cohort study. The inclusion criteria were AIS, age 10-16, VRB 23 h/day, X-rays available, primary curve 36°-65°, and angle of trunk rotation 7-23°.

Biallelic Variants Associated with Intellectual Disability and Neurodevelopmental Disorders Alter TRESK Channel Activity.

The TWIK-related spinal cord potassium channel (TRESK) is encoded by , and variants in this gene have previously been associated with susceptibility to familial migraine with aura (MIM #613656). A single amino acid substitution in the same protein, p.Trp101Arg, has also been associated with intellectual disability (ID), opening the possibility that variants in this gene might be involved in different disorders.

Diagnosis of maternal Hodgkin lymphoma following abnormal findings at noninvasive prenatal screening test (NIPT): Report of two cases.

Abnormal NIPT results, contrasting with normal fetus development, could disclose maternal malignancy, and this possibility should always be explained during pretest counseling. In this case, a complete diagnostic assessment is recommended and should be managed by a multidisciplinary team to define the best timing for diagnostic procedures, delivery, and treatment.

Atypical microdeletion 22q11.2 in a patient with tetralogy of Fallot.

The 22q11.2 microdeletion syndrome (22q11.2 DGS) is characterized by an extreme intrafamilial and interfamilial variability.

When to test fetuses for RASopathies? Proposition from a systematic analysis of 352 multicenter cases and a postnatal cohort.

Purpose: Recent studies have identified suggestive prenatal features of RASopathies (e.g., increased nuchal translucency [NT], cystic hygroma [CH], hydrops, effusions, congenital heart diseases [CHD], polyhydramnios, renal anomalies).

A novel case of congenital spinocerebellar ataxia 5: further support for a specific phenotype associated with the p.(Arg480Trp) variant in .

A 4-year-old girl was referred to the geneticist with a history of ataxia associated with intention tremor of the hands, strabismus and hypermetropy. Her symptoms presented about 2 years earlier with inability to walk unaided and lower limbs hypotonia. Cognitive functions were normal.

Comparison of the functional and structural characteristics of rare TSC2 variants with clinical and genetic findings.

The TSC1 and TSC2 gene products interact to form the tuberous sclerosis complex (TSC), an important negative regulator of the mechanistic target of rapamycin complex 1 (TORC1). Inactivating mutations in TSC1 or TSC2 cause TSC, and the identification of a pathogenic TSC1 or TSC2 variant helps establish a diagnosis of TSC. However, it is not always clear whether TSC1 and TSC2 variants are inactivating.

Congenital Sensorineural Hearing Loss and Inborn Pigmentary Disorders: First Report of Multilocus Syndrome in Piebaldism.

Congenital sensorineural hearing loss may occur in association with inborn pigmentary defects of the iris, hair, and skin. These conditions, named auditory-pigmentary disorders (APDs), represent extremely heterogeneous hereditary diseases, including Waardenburg syndromes, oculocutaneous albinism, Tietz syndrome, and piebaldism. APDs are part of the neurocristopathies, a group of congenital multisystem disorders caused by an altered development of the neural crest cells, multipotent progenitors of a wide variety of different lineages, including those differentiating into peripheral nervous system glial cells and melanocytes.

A fetal case of microphthalmia and limb anomalies with abnormal neuronal migration associated with SMOC1 biallelic variants.

Microphthalmia with limb anomalies (MLA, OMIM, 206920) is a rare autosomal-recessive disease caused by biallelic pathogenic variants in the SMOC1 gene. It is characterized by ocular disorders (microphtalmia or anophtalmia) and limb anomalies (oligodactyly, syndactyly, and synostosis of the 4th and 5th metacarpals), variably associated with long bone hypoplasia, horseshoe kidney, venous anomalies, vertebral anomalies, developmental delay, and intellectual disability. Here, we report the case of a woman who interrupted her pregnancy after ultrasound scans revealed a depression of the frontal bone, posterior fossa anomalies, cerebral ventricular enlargement, cleft spine involving the sacral and lower-lumbar vertebrae, and bilateral microphthalmia.

Angiomyolipoma rebound tumor growth after discontinuation of everolimus in patients with tuberous sclerosis complex or sporadic lymphangioleiomyomatosis.

Introduction: The EXIST-2 (NCT00790400) study demonstrated the superiority of everolimus over placebo for the treatment of renal angiomyolipomas associated with tuberous sclerosis complex (TSC) or sporadic lymphangioleiomyomatosis (LAM). This post hoc analysis of EXIST-2 study aimed to assess angiomyolipoma tumor behavior among patients who submitted to continued radiographic examination following discontinuation of everolimus in the noninterventional follow-up phase.

Methods: For patients who discontinued everolimus at the completion of extension phase for reasons other than angiomyolipoma progression, a single CT/MRI scan of the kidney was collected after 1 year of treatment discontinuation.

Copy number variants analysis in a cohort of isolated and syndromic developmental delay/intellectual disability reveals novel genomic disorders, position effects and candidate disease genes.

Background: Array-comparative genomic hybridization (array-CGH) is a widely used technique to detect copy number variants (CNVs) associated with developmental delay/intellectual disability (DD/ID).

Aims: Identification of genomic disorders in DD/ID.

Materials And Methods: We performed a comprehensive array-CGH investigation of 1,015 consecutive cases with DD/ID and combined literature mining, genetic evidence, evolutionary constraint scores, and functional information in order to assess the pathogenicity of the CNVs.

A novel synonymous mutation in the MPZ gene causing an aberrant splicing pattern and Charcot-Marie-Tooth disease type 1b.

Charcot-Marie-Tooth disease (CMT) is an inherited peripheral neuropathy with a heterogeneous genetic background. Here, we describe two CMT1B families with a mild sensory-motor neuropathy and a novel synonymous variant (c.309G > T, p.

Testing for the cytosine insertion in the VNTR of the MUC1 gene in a cohort of Italian patients with autosomal dominant tubulointerstitial kidney disease.

Introduction: Medullary cystic kidney disease type 1 (MCKD1; OMIM #174000) is a familial progressive tubule-interstitial nephropathy belonging to the recently defined group of autosomal dominant tubulointerstitial kidney diseases (ADTKD).

Case Report: A specific type of cytosine insertion in the extracellular variable number tandem repeat (VNTR) domain of the MUC1 gene causing the disease was tested in a group of 21 families with ADTKD. We identified this type of MUC1 mutation in two families, whose affected members are described in detail in this case report.

Clinical, neuroradiological and molecular characterization of cerebellar dysplasia with cysts (Poretti-Boltshauser syndrome).

Cerebellar dysplasia with cysts and abnormal shape of the fourth ventricle, in the absence of significant supratentorial anomalies and of muscular involvement, defines recessively inherited Poretti-Boltshauser syndrome (PBS). Clinical features comprise non-progressive cerebellar ataxia, intellectual disability of variable degree, language impairment, ocular motor apraxia and frequent occurrence of myopia or retinopathy. Recently, loss-of-function variants in the LAMA1 gene were identified in six probands with PBS.

Array-Comparative Genomic Hybridization Analysis in Fetuses with Major Congenital Malformations Reveals that 24% of Cases Have Pathogenic Deletions/Duplications.

Karyotyping and aCGH are routinely used to identify genetic determinants of major congenital malformations (MCMs) in fetal deaths or terminations of pregnancy after prenatal diagnosis. Pathogenic rearrangements are found with a variable rate of 9-39% for aCGH. We collected 33 fetuses, 9 with a single MCM and 24 with MCMs involving 2-4 organ systems.

Increasing the activity and enantioselectivity of lipases by sol-gel immobilization: further advancements of practical interest.

The entrapment of lipases in hydrophobic silicate matrices formed by sol-gel mediated hydrolysis of RSi(OCH3)3/Si(OCH3)4 as originally reported in 1996 has been improved over the years by a number of modifications. In the production of second-generation sol-gel lipase immobilizates, a variety of additives during the sol-gel process leads to increased activity and enhanced stereoselectivity in esterifying kinetic resolution. Recent advances in this type of lipase immobilization are reviewed here, in addition to new results regarding the sol-gel entrapment of the lipase from Burkholderia cepacia.

Life-threatening tumors of the heart in fetal and postnatal age.

Objectives: To evaluate the role of histology in diagnosis and management of biologically benign heart tumors causing life-threatening symptoms and even death in children and fetuses. The clinical impact of a multidisciplinary approach including 2-D echocardiography, histology, genetics, and cardiac surgery has not yet been fully elucidated.

Study Design: Forty-one consecutive antenatal (n = 17) or postnatal (n = 24) detected cardiac masses were evaluated by 2-D echocardiography (in alive patients) or at autopsy, and 12/41 cases with definite histologic diagnosis of primary and benign cardiac tumor were entered in this study.

Team care to cure adolescents with braces (avoiding low quality of life, pain and bad compliance): a case-control retrospective study. 2011 SOSORT Award winner.

Background: Bracing could be efficacious, given good compliance and quality of braces. Recently the SOSORT Brace TREATMENT Management Guidelines (SBTMG) have highlighted the perceived importance of the professional teams surrounding braced patients.

Purpose: To verify the impact of a complete rehabilitation team in the adolescent patient with bracing.

Cell death following BNCT: a theoretical approach based on Monte Carlo simulations.

In parallel to boron measurements and animal studies, investigations on radiation-induced cell death are also in progress in Pavia, with the aim of better characterisation of the effects of a BNCT treatment down to the cellular level. Such studies are being carried out not only experimentally but also theoretically, based on a mechanistic model and a Monte Carlo code. Such model assumes that: (1) only clustered DNA strand breaks can lead to chromosome aberrations; (2) only chromosome fragments within a certain threshold distance can undergo misrejoining; (3) the so-called "lethal aberrations" (dicentrics, rings and large deletions) lead to cell death.

Boron uptake measurements in a rat model for Boron Neutron Capture Therapy of lung tumours.

Lung carcinoma is the leading cause of cancer mortality in the Western countries. Despite the introduction over the last few years of new therapeutic agents, survival from lung cancer has shown no discernible improvement in the last 20 years. For these reasons any efforts to find and validate new effective therapeutic procedures for lung cancer are very timely.

In vitro and in vivo studies of boron neutron capture therapy: boron uptake/washout and cell death.

Boron neutron capture therapy (BNCT) is a binary radiotherapy based on thermal-neutron irradiation of cells enriched with (10)B, which produces α particles and (7)Li ions of short range and high biological effectiveness. The selective uptake of boron by tumor cells is a crucial issue for BNCT, and studies of boron uptake and washout associated with cell survival studies can be of great help in developing clinical applications. In this work, boron uptake and washout were characterized both in vitro for the DHDK12TRb (DHD) rat colon carcinoma cell line and in vivo using rats bearing liver metastases from DHD cells.