IL12B polymorphism and type 1 diabetes in the Italian population: a case-control study

A polymorphism in the interleukin 12B gene was recently reported to be strongly associated with type 1 diabetes in 422 Australian and British families. We analyzed the same polymorphism in 470 Italian type 1 diabetic patients and 544 matched control subjects and found no evidence of association with the disease.     

Homocysteine Lowering by Folate-Rich Diet or Pharmacological Supplementations in Subjects with Moderate Hyperhomocysteinemia

Background/Objectives: To compare the efficacy of a diet rich in natural folate and of two different folic acid supplementation protocols in subjects with “moderate” hyperhomocysteinemia, also taking into account C677T polymorphism of 5,10-methylenetetrahydrofolate reductase (MTHFR) gene. Subjects/Methods: We performed a 13 week open, randomized, double blind clinical trial on 149 free living persons with mild hyperhomocyteinemia, with daily 200 μg from a natural folate-rich diet, 200 μg [6S]5-methyltetrahydrofolate (5-MTHF), 200 μg folic acid or placebo. Participants were stratified according to their MTHFR genotype. Results: Homocysteine (Hcy) levels were reduced after folate enriched diet, 5-MTHF or folic acid supplementation respectively by 20.1% (p < 0.002), 19.4% (p < 0.001) and 21.9% (p < 0.001), as compared to baseline levels and significantly as compared to placebo (p < 0.001, p < 0.002 and p < 0.001, respectively for enriched diet, 5-MTHF and folic acid). After this enriched diet and the folic acid supplementation, Hcy in both genotype groups decreased approximately to the same level, with higher percentage decreases observed for the TT group because of their higher pre-treatment value. Similar results were not seen by genotype for 5-MTHF. A significant increase in RBC folate concentration was observed after folic acid and natural folate-rich food supplementations, as compared to placebo. Conclusions: Supplementation with natural folate-rich foods, folic acid and 5-MTHF reached a similar reduction in Hcy concentrations.     

Collagen Damage Location in Articular Cartilage Differs if Damage is Caused by Excessive Loading Magnitude or Rate

Collagen damage in articular cartilage is considered nearly irreversible and may be an early indication of cartilage degeneration. Surface fibrillation and internal collagen damage may both develop after overloading. This study hypothesizes that damage develops at these different locations, because the distribution of excessive strains varies with loading rate as a consequence of time-dependent cartilage properties. The objective is to explore whether collagen damage could preferentially occur superficially or internally, depending on the magnitude and rate of overloading. Bovine osteochondral plugs were compressed with a 2 mm diameter indenter to 15, 25, 35 and 45 N, and at 5, 60 and 120 mm/min. Surface fibrillation and internal collagen damage were graded by four observers, based on histology and staining of collagen damage. Results show that loading magnitude affects the degree of collagen damage, while loading rate dominates the location of network damage: low rates predominantly damage superficial collagen, while at high rates, internal collagen damage occurs. The proposed explanation for the rate-dependent location is that internal fluid flows govern the time-dependent internal tissue deformation and therewith the location of overstained and damaged areas. This supports the hypothesis that collagen damage development is influenced by the time-dependent material behaviour of cartilage.     

Targeting TRAP1 as a downstream effector of BRAF cytoprotective pathway: A novel strategy for human BRAF-driven colorectal carcinoma

The HSP90 chaperone TRAP1 is translational regulator of BRAF synthesis/ubiquitination, since BRAF down-regulation, ERK signaling inhibition and delay of cell cycle progression occur upon TRAP1 silencing/inhibition. Since TRAP1 is upregulated in human colorectal carcinomas (CRCs) and involved in protection from apoptosis and as human BRAF-driven CRCs are poorly responsive to anticancer therapies, the relationship between TRAP1 regulation of mitochondrial apoptotic pathway and BRAF antiapoptotic signaling has been further evaluated. This study reports that BRAF cytoprotective signaling involves TRAP1-dependent inhibition of the mitochondrial apoptotic pathway. It is worth noting that BRAF and TRAP1 interact and that the activation of BRAF signaling results in enhanced TRAP1 serine-phosphorylation, a condition associated with resistance to apoptosis. Consistently, a BRAF dominant-negative mutant prevents TRAP1 serine phosphorylation and restores drug sensitivity in BRAFV600E CRC drug-resistant cells with high TRAP1 levels. In addition, TRAP1 targeting by the mitochondria-directed HSP90 chaperones inhibitor gamitrinib induces apoptosis and inhibits colony formation in BRAF-driven CRC cells. Thus, TRAP1 is a downstream effector of BRAF cytoprotective pathway in mitochondria and TRAP1 targeting may represent a novel strategy to improve the activity of proapoptotic agents in BRAF-driven CRC cells.     

Severe respiratory distress at birth caused by a hairy polyp of the Eustachian tube: Transoral endoscopy‐guided treatment

Hairy polyps are rare developmental lesions, which present as masses mainly consisting of fatty tissue covered by skin, seldom localized in the nasopharynx, causing respiratory obstruction. We describe the case of a female newborn affected by a hairy polyp arising from the left Eustachian tube, who presented severe respiratory distress soon after birth. The polyp was successfully removed transorally under videoendoscopic guidance. This case highlights the importance of including hairy polyp in the differential diagnosis of respiratory distress at birth because this type of tumor can be lethal and requires prompt treatment. A transoral endoscopy‐guided approach can allow successful and minimally invasive excision even in a newborn.     

Differences in views of schizophrenia during medical education: a comparative study of 1st versus 5th–6th year Italian medical students

Purpose

This study explored medical students’ causal explanations and views of schizophrenia, and whether they changed during medical education.

Method

The survey was carried out on medical students of the Second University of Naples, Italy, who attended their first-year and their fifth- or sixth-year of lessons. The 381 who accepted were asked to read a case-vignette describing a person who met the ICD-10 criteria for schizophrenia and then fill in the Opinions on mental illness Questionnaire.

Results

The most frequently cited causes were psychological traumas (60 %) and stress (56 %), followed by misuse of street drugs (47 %), and heredity (42 %). 28 % of students stated that persons with the disorder could be well again, and 28 % that they were unpredictable. Labeling the case as “schizophrenia” and naming heredity among the causes were associated with pessimism about recovery and higher perception of social distance. First-year students more frequently reported psychological traumas among the causes (76 vs. 45 %), and less frequently heredity (35 vs. 81 %) and stress (42 vs. 69 %), and they perceived less social distance from the “schizophrenics” than fifth/sixth-year students. In particular, 18 % percent of first-year versus 38 % of fifth/sixth-year students believed that these persons were kept at a distance by the other, and 45 versus 57 % felt frightened by persons with the condition.

Conclusions

These results indicate a need to include education on stigma and recovery in schizophrenia in the training of medical students.     

Cytarabine and clofarabine after high‐dose cytarabine in relapsed or refractory AML patients

Clofarabine has been shown to be effective in AML patients, either as single agent or, mainly, in association with intermediate dose cytarabine. Based on these reports, we conducted a preliminary study combining clofarabine and intermediate dose cytarabine in AML patients who relapsed or failed to respond to at least two induction therapies. We treated 47 patients affected by relapsed/refractory AML with a regimen including clofarabine at 22.5 mg/m² daily on days 1–5, followed after 3 hr by cytarabine at 1 g/m² daily on days 1–5. Ten patients received a further consolidation cycle with clofarabine at 22.5 mg/m² and cytarabine at 1 g/m² day 1–4. Among the 47 patients, 24/47 (51%) achieved a complete remission, 5/47 (10.5%) a partial response, 10/47 (21%) had a resistant disease, and 6/47 (13%) died of complications during the aplastic phase. The most frequent nonhematologic adverse events were vomiting, diarrhea, transient liver toxicity, febrile neutropenia, and infections microbiologically documented. Among the 24 patients who obtained a CR 13 underwent allogeneic bone marrow transplantation. In 14 patients, complete remission duration was shorter than 12 months, whereas 10 patients experienced longer complete remission duration. These very preliminary results suggest that clofarabine‐cytarabine regimen is effective in this particularly poor prognosis category of patients, representing a potential “bridge” toward bone marrow transplant procedures. Safety data were consistent with previously reported salvage therapies. Further studies and a longer follow up are warranted. Am. J. Hematol., 2012. © 2012 Wiley Periodicals, Inc.