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Introduction: This work aims to provide an updated overview of the eating disorders (EDs) which are a widespread pathology nowadays. Informations related to the clinical-nosographic characteristics, an in-depth analysis about systemic-relational theories and historical evolution are provided. In addition, current informations about epidemiological data, recovery, treatment related implications, new neuroscientific theories and risk factors are shown. Given the complexity of these disorders, the lack of resources and the the increasing demands for treatment, the main object is related to the construction of a questionnaire to manage the waiting lists. Objectives: Building a waiting list management model for EDs, Study and compare advantages and disadvantages of the source allocation ethical models (utilitarianism, prioritarianism, egalitarianism), Analyze EDs leading experts (doctors, dietitians, psychologists, psychiatrists) and EDs patients positioning with respect to priority treatment factors. Promote constructive dialog between EDs experts from different backgrounds and EDs patients. Methods: In order to know the various treatment alternatives available, the different levels and reference structures are illustrated. In addition, it is also suggested different reasoning based on the ethical models of egalitarianism, utilitarianism and prioritarianism in order to build a waiting list management model, which is the maximum goal of this work. This model needs to be supported by a series of validated tools such as the clinical interview and self-administered questionnaires to investigate psychopathological aspects and psychiatric symptoms. Going into more details, a questionnaire is proposed to the EDs leading experts, so that they can provide their own priority factors list and related thoughts in order to build "the most ethical" waiting list. Results: It is expected that both patients and clinicians tend to give priority to patients with greater psychophysical severity, not exclusively on the basis of physical parameters. Further hypothesis related to clinicians lead us believe that they tend to use utilitarian logics, in compliance with the demonstrated efficacy of early intervention. An evaluation that could lead to a disagreement between experts and patients is related to prioritize patients in the initial phase of the disease, which could be supported by clinicians, but not by patients, probably in connection with their personal experiences. In fact, this favoritism could have a negative impact on the care of the most serious cases who risk to be left to themselves. Conclusions: This work aims to encourage a constructive dialogue between experts and patients with EDs in order to build a functional intervention model which should be "the most ethical as possible" in order to save the greatest number of lives in respect of mental suffering. Disclosure of Interest: None Declared [ABSTRACT FROM AUTHOR]

Neutrinos (ν) are produced in practically all extragalactic astrophysical processes. They can travel enormous distances from remote parts of the universe at velocities near the speed of light. The interaction of neutrinos with both galactic and extragalactic particles may shed light on the composition of these particles. Dark matter (DM) is perhaps the most favored candidate for such intra- and extragalactic media. In this paper, we study the interaction of neutrinos with cold leptonic DM at the relativistic level. We have calculated cross-sections for the ν –DM interactions by adopting different models for the DM distribution, in order to test DM properties. [ABSTRACT FROM AUTHOR]

Neutrinos in astrophysical environments, such as Supernovae (SNe), may interact through pair interactions. These interactions are density and temperature-dependent. Under certain conditions, a neutrino-condensate may form. In this work, we have adapted the separable nonlocal pairing interactions to the SN conditions and studied the temperature and density dependence of the pairing gap as well as the collective response with respect to these variables. We have applied the Bogoliubov transformations and solved the Bardeen, Cooper and Schrieffer (BCS) equations to construct the free quasi-particle sector of the Hamiltonian. The residual two-quasi-particle terms have been treated by applying the Tamm–Dancoff approximation (TDA) and random-phase approximation (RPA), suited to the extended neutrino media. With this, we have constructed neutrino energy distributions both in the superfluid and normal regimes and extracted critical values of the density and temperature. [ABSTRACT FROM AUTHOR]

Classical Ehlers-Danlos syndrome ( cEDS) is characterized by marked cutaneous involvement, according to the Villefranche nosology and its 2017 revision. However, the diagnostic flow-chart that prompts molecular testing is still based on experts' opinion rather than systematic published data. Here we report on 62 molecularly characterized cEDS patients with focus on skin, mucosal, facial, and articular manifestations. The major and minor Villefranche criteria, additional 11 mucocutaneous signs and 15 facial dysmorphic traits were ascertained and feature rates compared by sex and age. In our cohort, we did not observe any mandatory clinical sign. Skin hyperextensibility plus atrophic scars was the most frequent combination, whereas generalized joint hypermobility according to the Beighton score decreased with age. Skin was more commonly hyperextensible on elbows, neck, and knees. The sites more frequently affected by abnormal atrophic scarring were knees, face (especially forehead), pretibial area, and elbows. Facial dysmorphism commonly affected midface/orbital areas with epicanthal folds and infraorbital creases more commonly observed in young patients. Our findings suggest that the combination of ≥1 eye dysmorphism and facial/forehead scars may support the diagnosis in children. Minor acquired traits, such as molluscoid pseudotumors, subcutaneous spheroids, and signs of premature skin aging are equally useful in adults. [ABSTRACT FROM AUTHOR]

Release from growth factor dependence and acquisition of signalling pathway addiction are critical steps in oncogenesis. To identify genes required on mammalian target of rapamycin (mTOR) addiction, we performed a genome-wide short hairpin RNA screen on a v-H-ras-transformed Pten-deficient cell line that displayed two alternative growth modes, interleukin (IL)-3-independent/mTOR-addicted proliferation (transformed growth mode) and IL-3-dependent/mTOR-non-addicted proliferation (normal growth mode). We screened for genes required only in the absence of IL-3 and thus specifically for the transformed growth mode. The top 800 hits from this conditional lethal screen were analyzed in silico and 235 hits were subsequently rescreened in two additional Pten-deficient cell lines to generate a core set of 47 genes. Hits included genes encoding mTOR and the mTOR complex 2 (mTORC2) component rictor and several genes encoding mitochondrial functions including components of the respiratory chain, adenosine triphosphate synthase, the mitochondrial ribosome and mitochondrial fission factor. Small interfering RNA knockdown against a sizeable fraction of these genes triggered apoptosis in human cancer cell lines but not in normal fibroblasts. We conclude that mTORC2-addicted cells require mitochondrial functions that may be novel drug targets in human cancer. [ABSTRACT FROM AUTHOR]

Abstract: Heritage language speakers constitute a unique cultural and linguistic resource in the United States while also presenting particular challenges for language educators and language programs. This paper examines the potential of systemic functional linguistics (SFL) in a curriculum for Spanish second language learners/heritage speakers, with particular emphasis on the meaning-making of language in the construal of discourse. Following SFL pedagogy, descriptive language teaching refers to ways of treating language in functional terms; productive language teaching involves students in using the resource of their language in powerful ways in light of the demands of particular social contexts. Many heritage speakers have developed their heritage language (Spanish) in the family context but want to be able to use it in the professional areas. SFL with its explicit focus on language allows for the development of advanced literacy in a heritage language in the educational context. Accordingly, the paper discusses explicit instruction of genre/register theory as a way of promoting students’ awareness of discourse-semantics and lexicogrammatical features of academic language in courses for heritage speakers. Students’ success in developing academic registers in Spanish is evident in their use of lexicogrammatical features (such as grammatical metaphor) that index academic writing. [Copyright &y& Elsevier]

Retroviral integration mutagenesis and treatment with the frameshift mutagen ICR191 were used to transform v-H-ras expressing PB-3c cells to interleukin-3 (IL-3) independence. Six clones displayed viral integrations into the 3′ region of the IL-3 gene thus acting post-transcriptionally by disrupting the AU-rich instability element. Two clones contained reverse orientation integration into the raf-1 gene revealing an enhancer insertion mechanism. Growth by this mechanism was sensitive to the Raf-1 inhibitor BAY 43-9006 and the Mek inhibitor U0126. Following treatment with ICR191, IL-3-independent clones were recovered and studied by cell fusion. With 21/22 clones, IL-3 independence resulted from a recessive mechanism as cellular hybrids with parental cells reverted to IL-3 dependence. Recessive clone D2c displayed increased phospho-Erk1/2 levels and was growth sensitive to U0126, but not to BAY43-9006. The single dominant clone, D5a, showed no signs of mitogen-activated protein kinases pathway activation but displayed constitutive phosphorylation of Stat5. We conclude that PB-3c has several options to acquire IL-3 growth autonomy involving transcriptional or post-transcriptional mechanisms affecting the distal regulators Erk or Stat5. The reported panel of independent dominant and recessive transformants should provide a useful tool for inhibitor profiling.Oncogene (2006) 25, 6595–6603. doi:10.1038/sj.onc.1209673; published online 15 May 2006 [ABSTRACT FROM AUTHOR]

We verified the diagnostic and prognostic role of a simplified immunophenotypic classification (IC) in a series of 258 patients (M/F: 1.4; median age: 64 years; median follow-up: 64 months; 75 deaths) with mature B cell lymphoid leukemias (MBC-LL) for whom no histopathological diagnosis was available because of minimal or no lymph node involvement. The IC was based on the reactivity of three pivotal immunophenotypic markers: CD5, CD23 and SIg intensity. On the basis of different expression patterns, we identified four diagnostic clusters (C) characterized by distinct clinico-biological features and different prognoses: C1 (149 patients) identified most classical B cell chronic lymphocytic leukemias (CLL-type cluster; SIg[SUPdim]/CD5[SUP+]/CD23[SUP+]); C2, 38 patients whose clinico-hematological characteristics were intermediate between C1 and C3 (CLL-variant cluster; SIg[SUPbright]/CD5[SUP+]/CD23[SUP+/-] or SIg[SUPdim]/CD5[SUP-/-]/CD23 indifferent); C3 (16 patients) most situations consistent with mantle cell lymphoma in leukemic phase (MCL-type cluster; SIg[SUPbright]/CD5[SUP+]/CD23[SUP-]); and C4, 55 cases, most of whom were consistent with leukemic phase lymphoplasmacytic/splenic marginal zone lymphomas (LP/S-type cluster; SIg[SUPbright]/CD5[SUP-/+]/CD23 indifferent). At univariate survival analysis, prognosis worsened from C1 to C4, C2 and C3 (P = 0.0001), and this was maintained at multivariate analysis (P = 0.006), together with CD11c expression (P = 0.0043), age at diagnosis (cut-off 70 years; P = 0.0008) and platelet count (cut-off 140 × 10[SUP9]/l; P = 0.0034). Besides recognising the two well-known situations of classic B-CLL and MCL, our IC identified situations with distinct prognostic and/or clinical behaviors. [ABSTRACT FROM AUTHOR]

Arterial tortuosity syndrome (ATS) is a rare autosomal recessive disorder caused by mutations in the solute carrier family 2 member 10 (SLC2A10) gene encoding a glucose/ascorbic acid transporter. The clinical features of ATS are mild-to-severe tortuosity of the large and medium arteries throughout the body, accompanied by dysmorphisms and joint laxity. Vascular changes in different parts of the body lead to stenosis and/or aneurysms requiring difficult surgical procedures. Here we present two new patients with ATS from two unrelated families. Patient 1 presented at 10 years of age with headache and typical physical appearance, delicate skeleton, large visible pulsation of the carotid arteries in the neck, and joint laxity. On computed tomography (CT) angiography she had severe tortuosity of the aortal branches and cerebral arteries, but no significant tortuosity of the pulmonary arteries. Two cousins of the girl carried the same homozygous c.254T>C, p.(Leu85Pro) mutation in SLC2A10, however, they additionally had a severe involvement of the pulmonary vessels. Patient 2 was a 9-year-old girl diagnosed with severe tortuosity and stenosis of the pulmonary arteries and progressive myocardiopathy. Her physical appearance was very similar to Patient 1, except that she also had growth retardation. After long-term follow-up by cardiologists, she underwent cardiac surgery abroad, with an unfavorable outcome. Homozygosity for the c.685C>T, p.(Arg229*) mutation in the SLC2A10 gene was detected. Consanguinity was disclosed within both families. Our findings confirm the intrafamilial phenotype variability of ATS. A novel finding is the severe tortuosity of cerebral arteries causing migraine that has not been described before in a child with ATS. [ABSTRACT FROM AUTHOR]

Deletions encompassing TAK1-binding protein 2 ( TAB2) associated with isolated and syndromic congenital heart defects. Rare missense variants are found in patients with a similar phenotype as well as in a single individual with frontometaphyseal dysplasia. We describe a family and an additional sporadic patient with polyvalvular heart disease, generalized joint hypermobility and related musculoskeletal complications, soft, velvety and hyperextensible skin, short limbs, hearing impairment, and facial dysmorphism. In the first family, whole-exome sequencing (WES) disclosed the novel TAB2 c.1398dup (p. Thr467Tyrfs*6) variant that eliminates the C-terminal zinc finger domain essential for activation of TAK1 ( TGFβ-activated kinase 1)-dependent signaling pathways. The sporadic case carryed a ~2 Mb de novo deletion including 28 genes also comprising TAB2. This study reveal an association between TAB2 mutations and a phenotype resembling Ehlers-Danlos syndrome with severe polyvalvular heart disease and subtle facial dysmorphism. Our findings support the existence of a wider spectrum of clinical phenotypes associated with TAB2 perturbations and emphasize the role of TAK1 signaling network in human development. [ABSTRACT FROM AUTHOR]

Previous studies have reported an increased prevalence of osteoporosis in Ehlers–Danlos syndrome (EDS), but these were limited by a small number of patients and lack of information on fragility fractures. In this cross-sectional study, we evaluated the prevalence of radiological vertebral fractures (by quantitative morphometry) and bone mineral density (BMD, at lumbar spine, total hip and femoral neck by dual-energy X-ray absorptiometry) in 52 consecutive patients with EDS (10 males, 42 females; median age 41 years, range: 21–71; 12 with EDS classic type, 37 with EDS hypermobility type, 1 with classic vascular-like EDS, and 2 without specific classification) and 197 control subjects (163 females and 34 males; median age 49 years, range: 26–83) attending an outpatient bone clinic. EDS patients were also evaluated for back pain by numeric pain rating scale (NRS-11).Vertebral fractures were significantly more prevalent in EDS as compared to the control subjects (38.5% vs. 5.1%; p < 0.001) without significant differences in BMD at either skeletal sites. In EDS patients, the prevalence of vertebral fractures was not significantly ( p = 0.72) different between classic and hypermobility types. BMD was not significantly different between fractured and non-fractured EDS patients either at lumbar spine ( p = 0.14), total hip ( p = 0.08), or femoral neck ( p = 0.21). Severe back pain (≥ 7 NRS) was more frequent in EDS patients with vertebral fractures as compared to those without fractures (60% vs. 28%; p = 0.04). In conclusion, this is the first study showing high prevalence of vertebral fractures in a relatively large population of EDS patients. Vertebral fractures were associated with more severe back pain suggesting a potential involvement of skeletal fragility in determining poor quality of life. The lack of correlation between vertebral fractures and BMD is consistent with the hypothesis that bone quality may be impaired in EDS. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 36-year-old man with haemorrhagic blisters, erosions and atrophic scarring in localized-exposed sites. Result of immunofluorescence analysis shows a slightly attenuated COLVII linear staining at the dermal epidermal junction (DEJ), compared with control skin. The outcome of the COL7A1 expression analysis in the patient's cells also demonstrates that one allele is functionally null at the mRNA level, as the linked mutation prevents mRNA and PTC formation.

A letter to the editor is presented which shows the identification of a novel TGFBR1 mutation in a Loeys-Dietz syndrome (LDS) type II patient with vascular Ehlers-Danlos syndrome phenotype.

The article reports the clinical and molecular study conducted to an Italian family affected with Vohwinkel syndrome (VS) ichthyotic variant of loricrin keratoderma (LK) and its molecular characterization. Each patient is detailedly described and studied. The study reported new insights on LK genotype-phenotype correlation and that variabilities among the patients must be dealt as phenotypic continuum. It hypothesizes the presence of other genetic factors.

Dystrophic epidermolysis bullosa (DEB) pruriginosa (DEB-Pr) is a rare variant of DEB due to COL7A1 dominant and recessive mutations, which is characterized by severe itching and lichenoid or nodular prurigo-like lesions, mainly involving the extremities. Less than 30 patients have been described showing variable disease expression, and frequently, delayed age of onset. We report the clinical and molecular characterization of seven Italian DEB patients, three affected with recessive DEB-Pr and four with dominant DEB-Pr. In all the patients, the signs were typical of a mild DEB phenotype, until the onset of pruritus, which was followed by worsening of the clinical picture, with appearance of the distinctive lichenified lesions of DEB-Pr. Nine mutations were found in the COL7A1 gene, three of which were novel and one was de novo. DEB-Pr patients with either dominant or recessive mutations were shown to synthesize a normal or variably reduced amount of type VII collagen, which was correctly deposited at the dermal–epidermal junction. Since six of these mutations have been reported in DEB patients in the absence of intense pruritus, these data implicate a role of yet unidentified phenotype-modifying factors in the pathogenesis of DEB-Pr. [ABSTRACT FROM AUTHOR]

Summary Background Dystrophic epidermolysis bullosa (DEB) is a bullous skin disease caused by mutations in the type VII collagen gene (COL7A1 ). Objectives To elucidate the mutations shown by two patients with DEB and understand the clinical phenotypes that they displayed. Methods We have characterized two patients, one affected by the severe recessive Hallopeau–Siemens variant of DEB (HS-RDEB) and the other by a milder recessive DEB form. Results In both patients we identified the R2063W missense mutation. The second mutation, in the HS-RDEB patient, was a novel 344insG, leading to a premature termination codon of translation (PTC) in exon 3, while, in the other patient, it was a novel 4965C→T transition, which creates a new donor splice site in exon 53. The effect of this anomalous splice site leads to the maturation of a 17-nucleotides-deleted mRNA containing a PTC. In addition to this aberrant transcript, a certain amount of full-length mRNA is also generated from the mutated pre-mRNA through splicing at the canonical site. Conclusions In these patients therefore the severity of the phenotype depends on the second mutation. In the patient with the 344insG mutation, leading to a PTC, type VII collagen (COLVII) molecules are exclusively composed of chains containing the R2063W substitution; as a consequence, all anchoring fibrils (AF) are abnormal and the phenotype is severe. In the other patient, the 4965C→T splicing mutation allows the synthesis of a certain quantity of normal chains and the consequent assembly of partially functional COLVII molecules and AF, thus explaining the mild phenotype. [ABSTRACT FROM AUTHOR]

Dystrophic epidermolysis bullosa (DEB) is a rare genetic skin disorder. In this report we have investigated an Italian child affected with recessive DEB (RDEB) and demonstrated that he was homozygous for the mutation R226X in the type VII collagen gene (COL7A1), leading to absence of type VII collagen at the dermal–epidermal junction. There was no family history of inherited skin blistering but the child's father was affected by Marfan syndrome, an autosomal dominant connective tissue disorder that results from mutations in the fibrillin-1 gene (FBN1). Analysis of this gene showed that the RDEB patient and his father were both heterozygous for a novel FBN1 mutation, C1971Y. This mutation affects one of the six obligate cysteine residues within one of the calcium-binding epidermal growth factor-like regions of the protein. At the age of 2-years the RDEB patient showed signs of early aortic dilatation, suggesting that he is likely to develop a Marfan syndrome phenotype in the future. This is a unique case of these two coexisting inherited disorders. [ABSTRACT FROM AUTHOR]

Previous investigations have shown that skin fibroblasts derived from patients affected by Ehlers–Danlos syndrome (EDS) lack an organized extracellular matrix (ECM) of fibronectin (FN). As retarded wound healing is a sign of EDS, we hypothesized that a young healthy man suffering from chronic recalcitrant leg ulcers might be affected by a defect of FN–ECM organization similar to that observed in EDS. Immunofluorescence of cultured skin fibroblasts obtained from skin biopsies from the patient and a control demonstrated that the patient’s fibroblasts lacked FN–ECM organization, in contrast with those of the control; this was restored by 10-7 mol/L dexamethasone (DEX) in vitro. DEX treatment of the patient was associated with healing of his leg ulcers. In conclusion, DEX may be effective in reversing impaired wound healing associated with a lack of FN–ECM organization. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Recurrence of the p.R156X TNNI2 Mutation in Distal Arthrogryposis Type 2B" in the 2006 issue.

The article presents a case study an Italian patient with dystrophic epidermolysis bullosa (DEB) and history of bilateral mitten hand surgery, obstructive sleep apnoea syndrome and mild dysphagia of solid food. The pat ient was analyzed with COL7A1 mutational screening and it was found that the expression of wild-type protein is not sufficient for dermal epidermal adhesion.