Relationship between the 46/1 haplotype of the JAK2 gene and the JAK2 mutational status and allele burden,the initial findings,and the survival of patients with myelofibrosis

An association has been reported between a specific haplotype of the JAK2 gene, the homozygous 46/1 haplotype, and a predisposition to the development of chromosome Philadelphia-negative myeloproliferative neoplasms. Concerning myelofibrosis (MF), controversy remains on the relationship between the above JAK2 haplotype and the patients’ clinicohematological features and survival. Among 132 patients with MF (60 % primary MF, 20 % postpolycythemia vera MF, 20 % post-essential thrombocythemia MF; 59 % JAK2V617F positive) who were analyzed for the JAK2 46/1 haplotype, 29 were found to be homozygous and 53 heterozygous. The homozygous 46/1 haplotype was more often observed in JAK2V617F-positive patients (29.5 versus 11 %, p?=?0.012). Moreover, among JAK2V617F-positive patients, those who were homozygous for the 46/1 haplotype had a higher allele burden than the remainder (92 versus 48 %, p?=?0.0017). Overall, patients with homozygous 46/1 haplotype showed significantly higher hemoglobin values and higher leukocyte counts, but no association was seen with other clinicohematological features. Finally, no relationship was observed between the JAK2 46/1 haplotype and either the patients’ prognostic score or survival.     

Toll-like receptors,immunoproteasome and regulatory T cells in children with Henoch–Schönlein purpura and primary IgA nephropathy

Background

Henoch–Schönlein purpura (HSP) nephritis and primary IgA nephropathy (pIgAN) present with glomerular IgA deposits, but differ with regard to clinical features. The suspected involvement of different immune system pathways is largely unknown.

Methods

This study was aimed at investigating some of the immunological features including Toll-like receptors (TLR), proteasome (PS)/immunoproteasome (iPS) switch, and the regulatory T cell system (Treg/Th17 cells) in 63 children with HSP with/without renal involvement and in 25 with pIgAN. Real-time PRC (Taqman) was used to quantify mRNA levels in peripheral blood mononuclear cells (PBMC).

Results

The expression of mRNAs encoding for TLR4 in both HSP and pIgAN was higher than in controls (HC) and in both diseases FoxP3mRNA and TGF-β1mRNA expression was significantly lower than in HC. A switch from PS to iPS (LMP2/β1) was detected only in PBMC of HSP and it correlated with the level of TLR2mRNA, which was selectively increased only in children with HSP.

Conclusion

Children with HSP and pIgAN present with similar signs of engagement of the innate immunity and regulatory T cell depression. The increased immunoproteasome switch, which correlated with TLR2 activation, may suggest an innate immunity pathway peculiar to HSP vasculitic presentation. This research area also deserves further investigation for possible therapeutic applications.     

Information and communication technology in chronic diseases: a patient’s opportunity

The increasing aging population, the prevalence of chronic diseases and rising costs have brought about some unique health care challenge to our global society. In response to the unmet health care needs, researchers are actively seeking for innovative solutions that target for (1) prevention of diseases and (2) personalized diagnosis and treatment. It is envisaged that by taking preventive measures for health monitoring, diagnosing and treating patients with a personalized approach at an early stage of disease development, health care will be more cost effective and sustainable. The authors provide an overview of the advancements in Information and Communication Technology (ICT), and explain how some innovative health solutions, through the use of Telemedicine, can now be an opportunity for patients and their family.     

Autophagy modulators for the treatment of oral and esophageal squamous cell carcinomas

Oral squamous cell carcinomas (OSCC) and esophageal squamous cell carcinomas (ESCC) exhibit a survival rate of less than 60% and 40%, respectively. Late-stage diagnosis and lack of effective treatment strategies make both OSCC and ESCC a significant health burden. Autophagy, a lysosome-dependent catabolic process, involves the degradation of intracellular components to maintain cell homeostasis. Targeting autophagy has been highlighted as a feasible therapeutic strategy with clinical utility in cancer treatment, although its associated regulatory mechanisms remain elusive. The detection of relevant biomarkers in biological fluids has been anticipated to facilitate early diagnosis and/or prognosis for these tumors. In this context, recent studies have indicated the presence of specific proteins and small RNAs, detectable in circulating plasma and serum, as biomarkers. Interestingly, the interplay between biomarkers (eg, exosomal microRNAs) and autophagic processes could be exploited in the quest for targeted and more effective therapies for OSCC and ESCC. In this review, we give an overview of the available biomarkers and innovative targeted therapeutic strategies, including the application of autophagy modulators in OSCC and ESCC. Additionally, we provide a viewpoint on the state of the art and on future therapeutic perspectives combining the early detection of relevant biomarkers with drug discovery for the treatment of OSCC and ESCC.     

Lymphoproliferative disorders in Sotos syndrome: Observation of two cases

Sotos syndrome is included among the overgrowth disorders, most of which have an increased risk of neoplasms. Sotos syndrome does not appear to be related to a specific tumor type, but rather to the development of solid tumors of ectodermal or mesodermal origin in general. We report on two Sotos syndrome patients who developed a non-Hodgkin lymphoma and an acute lymphoblastic leukaemia, respectively. Our experience suggests that there may exist a high frequency of lymphoproliferative disorders in Sotos syndrome, and points out the importance of a long-term follow-up of Sotos syndrome patients, to detect a possible neoplastic evolution. © 1996 Wiley-Liss, Inc.     

Effect of Enamel Pretreatment with Pastes Presenting Different Relative Dentin Abrasivity (RDA) Values on Orthodontic Bracket Bonding Efficacy of Microfilled Composite Resin: In Vitro Investigation and Randomized Clinical Trial

Bonding failure is a clinical issue frequently encountered in orthodontic practice. The aim of this study was to evaluate enamel pretreatment both in vitro and clinically using agents with different RDA values before brackets’ bonding, to assess if RDA can affect the Shear Bond Strength (SBS), Adhesive Remnant Index (ARI) and clinical failure rate of orthodontic brackets. For the in vitro study, 220 bovine teeth were pretreated with agents with different RDA values. Subsequently, brackets were bonded. For the clinical study, 20 patients underwent bonding of 20 brackets each with a split-mouth design. Low and high RDA toothpastes were used for enamel pretreatment. SBS, ARI and failures were recorded. Higher SBS values were found for teeth pretreated with lower RDA agents; conversely, lower SBS values were found for teeth pretreated with higher RDA agents (p < 0.05). For high ARI values, RDA increased too (p > 0.05). In the clinical study, a significantly lower failure rate was reported for teeth pretreated with low RDA toothpaste (2.5% in low RDA group, 7.0% in high RDA group; p < 0.05). No significant differences were assessed comparing the two dental arches and anterior and posterior sites. Enamel pretreatment with low RDA toothpastes could increase brackets’ survival rate. Further in vitro and clinical studies would be welcomed to confirm these findings.     

A Reverse Dynamical Investigation of the Catastrophic Wood-Snow Avalanche of 18 January 2017 at Rigopiano,Gran Sasso National Park,Italy

On 18 January 2017 a catastrophic avalanche destroyed the Rigopiano Gran Sasso Resort & Wellness(Rigopiano Hotel) in the Gran Sasso National Park in Italy,with ...