Crtap and p3h1 knock out zebrafish support defective collagen chaperoning as the cause of their osteogenesis imperfecta phenotype.

Prolyl 3-hydroxylation is a rare collagen type I post translational modification in fibrillar collagens. The primary 3Hyp substrate sites in type I collagen are targeted by an endoplasmic reticulum (ER) complex composed by cartilage associated protein (CRTAP), prolyl 3-hydroxylase 1 (P3H1) and prolyl cis/trans isomerase B, whose mutations cause recessive forms of osteogenesis imperfecta with impaired levels of α1(I)3Hyp986. The absence of collagen type I 3Hyp in wild type zebrafish provides the unique opportunity to clarify the role of the complex in vertebrate. Zebrafish knock outs for crtap and p3h1 were generated by CRISPR/Cas9. Mutant fish have the typical OI patients' reduced size, body disproportion and altered mineralization. Vertebral body fusions, deformities and fractures are accompanied to reduced size, thickness and bone volume. Intracellularly, collagen type I is overmodified, and partially retained causing enlarged ER cisternae. In the extracellular matrix the abnormal collagen type I assembles in disorganized fibers characterized by altered diameter. The data support the defective chaperone role of the 3-hydroxylation complex as the primary cause of the skeletal phenotype.

Zebrafish Collagen Type I: Molecular and Biochemical Characterization of the Major Structural Protein in Bone and Skin.

Over the last years the zebrafish imposed itself as a powerful model to study skeletal diseases, but a limit to its use is the poor characterization of collagen type I, the most abundant protein in bone and skin. In tetrapods collagen type I is a trimer mainly composed of two α1 chains and one α2 chain, encoded by COL1A1 and COL1A2 genes, respectively. In contrast, in zebrafish three type I collagen genes exist, col1a1a, col1a1b and col1a2 coding for α1(I), α3(I) and α2(I) chains. During embryonic and larval development the three collagen type I genes showed a similar spatio-temporal expression pattern, indicating their co-regulation and interdependence at these stages. In both embryonic and adult tissues, the presence of the three α(I) chains was demonstrated, although in embryos α1(I) was present in two distinct glycosylated states, suggesting a developmental-specific collagen composition. Even though in adult bone, skin and scales equal amounts of α1(I), α3(I) and α2(I) chains are present, the presented data suggest a tissue-specific stoichiometry and/or post-translational modification status for collagen type I. In conclusion, this data will be useful to properly interpret results and insights gained from zebrafish models of skeletal diseases.

Transient bacteraemia due to Chryseobacterium indologenes in an immunocompetent patient: a case report and literature review.

A 51-year-old woman was admitted to the emergency unit with diffuse headache, visus reduction, and paraesthesias of the trigeminal area and the left hand. Three days after admission she showed shaking chills, vomiting, and sudden onset of fever (39·4°C). Blood cultures were performed soon after fever onset. Fever persisted for the whole day, decreasing slowly after 12 hours. No empirical antibiotic treatment was started in order to better define the diagnosis. Fever completely disappeared the day after. Two blood cultures for aerobes were positive for Chryseobacterium indologenes. The patient was discharged with the diagnosis of transient bacteraemia and transferred to the neurology unit for further investigations. C. indologenes infections are described in 31 studies with a total of 171 cases (pneumonia and bacteraemia being the most frequent). Our case is the first report of transient bacteraemia caused by C. indologenes in an immunocompetent, non-elderly patient without needing medical devices.

Care taker blogs in caregiver fabricated illness in a child: a window on the caretaker's thinking?

Three recently diagnosed cases of caregiver-fabricated illness in a child at Seattle Children's Hospital shed light on a new manifestation of their caretakers' attention seeking. The patients' mothers were actively blogging about their children's reputed illnesses. Although it is not uncommon for parents of chronically ill children to blog about their child's medical course, specific themes in these blogs of parents suspected of medically abusing their children were noted. In particular, gross distortions of the information parents had received from medical providers were presented online, describing an escalation of the severity of their children's illnesses. The mothers reported contacting palliative care teams and Wish organizations, independently from their medical providers' recommendations. They sought on-line donations for their children's health needs. We believe these blogs provide additional direct evidence of the suspected caregivers' fabrications. Although we have not performed formal content analysis, blogs might also provide insight into the caretakers' motivations. Protective Services and/or police investigators could consider querying the internet for blogs related to children at risk for caregiver-fabricated illness in a child. These blogs, if viewed in parallel with the children's medical records, could assist medical diagnosis and legal documentation of medical fabrication and assist in protective planning for the affected children.

Apoptosis and autophagy have opposite roles on imatinib-induced K562 leukemia cell senescence.

Imatinib, the anti-Abl tyrosine kinase inhibitor used as first-line therapy in chronic myeloid leukemia (CML), eliminates CML cells mainly by apoptosis and induces autophagy. Analysis of imatinib-treated K562 cells reveals a cell population with cell cycle arrest, p27 increase and senescence-associated beta galactosidase (SA-ß-Gal) staining. Preventing apoptosis by caspase inhibition decreases annexin V-positive cells, caspase-3 cleavage and increases the SA-ß-Gal-positive cell population. In addition, a concomitant increase of the cell cycle inhibitors p21 and p27 is detected emphasizing the senescent phenotype. Inhibition of apoptosis by targeting Bim expression or overexpression of Bcl2 potentiates senescence. The inhibition of autophagy by silencing the expression of the proteins ATG7 or Beclin-1 prevents the increase of SA-ß-Gal staining in response to imatinib plus Z-Vad. In contrast, in apoptotic-deficient cells (Bim expression or overexpression of Bcl2), the inhibition of autophagy did not significantly modify the SA-ß-Gal-positive cell population. Surprisingly, targeting autophagy by inhibiting ATG5 is accompanied by a strong SA-ß-Gal staining, suggesting a specific inhibitory role on senescence. These results demonstrate that in addition to apoptosis and autophagy, imatinib induced senescence in K562 CML cells. Moreover, apoptosis is limiting the senescent response to imatinib, whereas autophagy seems to have an opposite role.

[Trend of the asbestos related diseases mortality in workers of a company in the province Cremona which manufactured asbestos products]. / Andamento delle patologie e della mortalità asbesto correlate in lavoratori di un'azienda della provincia di Cremona che produceva manufatti in amianto.

The study analyzes the trend of asbestos-related diseases and mortality in workers of a company in the province of Cremona which manufactured asbestos products. It is confirmed that the exposure to a high concentration of asbestos fibers (estimated to more than 20 fibers/cc) strictly correlates with the onset of pathologies from asbestos. In the studied population were found 19 cases of neoplastic diseases (12 mesotheliomas and 7 bronchopulmonary carcinomas). This figure, compared to the company working population, which over the years has been an average of 80 units, while not enabling to calculate an incidence rate due to the lack of reliable data on population, is indicative of a very significant cause-effect relationship since these are neoplastic diseases that can still arise. So it is necessary to continue the health monitoring of formerly exposed workers and appropriate to try to extend it to all workers of the asbestos compartment.

Statistical evaluation and parameters of phlogosis in patients sensitized to cypress.

To assess the increasing sensitivity to cypress, we evaluated a group of allergic subjects living in Apulia who had been referred for respiratory symptoms to the Section for Allergic and Immunological Diseases (SAID) of Bari University Hospital in the period between January and March 2006, and compared them with a group evaluated during the same months of 2003. We submitted all patients to Skin Prick Tests (SPT) and Radio-Allergo-Sorbent Tests (RAST). Our data show that the percentage of people sensitised to cypress has increased from 28.6 percent (2003) to 65.5 percent (2006). By contrast, we observed no variations in sensitisation to other substances. Since according to data furnished by the Italian Association of Areobiology (AIA), Monitoring Center of Brindisi 1, there was a variation in the quantity of pollen grains in 2006 as compared to 2003, it seems conceivable that an increase in the amount of pollen grains, together with other factors may influence the increasing sensitization, like the volume and the brittleness of the grain. In addition, other allergo-immunologic parameters are evaluated in order to better evaluate this allergic phlogosis.

Incidence of multiple sclerosis in the town of Sassari, Sardinia, 1965 to 1985: evidence for increasing occurrence of the disease.

Prevalence studies carried out in Sardinia from 1975 suggest an increasing occurrence of MS. However, it is questionable whether this increase represents a real change in MS incidence or simply reflects longer survival. Data from 79 patients indicated the average annual incidence for the period 1965 through 1985 was 3.4 per 100,000. On December 31, 1985, the prevalence rate was 69 per 100,000. Evaluation of MS temporal trends showed a significant increase in MS incidence during the study period: values ranged around two per 100,000 in the triennial periods 1965-1967, 1968-1970, and 1971-1973, and around five in each triennium from 1977 onward.