The association of Greig syndrome and mastocytosis reveals the involvement of the hedgehog pathway in advanced mastocytosis.

Mastocytosis is a heterogeneous disease characterized by an abnormal accumulation of mast cells (MCs) in 1 or several organs. Although a somatic KIT D816V mutation is detected in ∼85% of patients, attempts to demonstrate its oncogenic effect alone have repeatedly failed, suggesting that additional pathways are involved in MC transformation. From 3 children presenting with both Greig cephalopolysyndactyly syndrome (GCPS, Mendelian Inheritance in Man [175700]) and congenital mastocytosis, we demonstrated the involvement of the hedgehog (Hh) pathway in mastocytosis. GCPS is an extremely rare syndrome resulting from haploinsufficiency of GLI3, the major repressor of Hh family members. From these familial cases of mastocytosis, we demonstrate that the Hh pathway is barely active in normal primary MCs and is overactive in neoplastic MCs. GLI3 and KIT mutations had a synergistic, tumorigenic effect on the onset of mastocytosis in a GCPS mouse model. Finally, Hh inhibitors suppressed neoplastic MC proliferation in vitro and extend the survival time of mice with aggressive systemic mastocytosis (ASM). This work revealed, for the first time, the involvement of Hh signaling in the pathophysiology of mastocytosis and demonstrated the cooperative effects of the KIT and Hh oncogenic pathways in mice with ASM, leading to the identification of new promising therapeutic targets.

Trends in hospitalization rates for psoriasis flares since the introduction of biologics: a time series in France between 2005 and 2015.

BACKGROUND: In the late 2000s, the introduction of biologics transformed the prognosis for patients with moderate-to-severe psoriasis. We hypothesized that treatment with biologics may associate with a reduction in the hospitalization rate for psoriasis flares. OBJECTIVE: To analyse changes over time in the hospitalization rate for psoriasis flares. METHODS: We included inpatient stays in any of nine French hospitals between 2005 and 2015 for a psoriasis flare, as documented in the national inpatient database. In two centres, we also analysed data from the individual patients' electronic medical records. RESULTS: A total of 3572 stays were included. The introduction of biologics was not associated with a decrease in the number of hospitalizations for a psoriasis flare; on the contrary, we observed a non-significant increase in the number of hospitalizations (13 hospitalizations for psoriasis flares per quarter per 10 000 beds). In the two-centre study, the introduction of biologics was associated with a significant increase in the hospitalization of patients receiving topical treatments only (520 hospitalizations per year per 10 000 beds) and those with a first psoriasis flare. CONCLUSION: The number of hospitalizations for a psoriasis flare tended to increase between 2005 and 2015. The availability of additional treatment options might have increased patient demand and/or broadened the indications in clinical practice.

Probable DRESS syndrome induced by IL-1 inhibitors.

Interleukin (IL)-1 inhibitors have been increasingly used for treating autoinflammatory diseases during the last 10 years, but the spectrum of their possible side effects is not yet fully known. Here, we bring physicians' attention to a new severe complication of IL-1 inhibitors, manifesting as a probable drug reaction with eosinophilia and systemic symptoms (DRESS) in two patients.

Automated CBED processing: sample thickness estimation based on analysis of zone-axis CBED pattern.

An automated processing of convergent beam electron diffraction (CBED) patterns is presented. The proposed methods are used in an automated tool for estimating the thickness of transmission electron microscopy (TEM) samples by matching an experimental zone-axis CBED pattern with a series of patterns simulated for known thicknesses. The proposed tool detects CBED disks, localizes a pattern in detected disks and unifies the coordinate system of the experimental pattern with the simulated one. The experimental pattern is then compared disk-by-disk with a series of simulated patterns each corresponding to different known thicknesses. The thickness of the most similar simulated pattern is then taken as the thickness estimate. The tool was tested on [0 1 1] Si, [0 1 0] α-Ti and [0 1 1] α-Ti samples prepared using different techniques. Results of the presented approach were compared with thickness estimates based on analysis of CBED patterns in two beam conditions. The mean difference between these two methods was 4.1% for the FIB-prepared silicon samples, 5.2% for the electro-chemically polished titanium and 7.9% for Ar(+) ion-polished titanium. The proposed techniques can also be employed in other established CBED analyses. Apart from the thickness estimation, it can potentially be used to quantify lattice deformation, structure factors, symmetry, defects or extinction distance.

Attitudes towards mental health care in younger and older adults: similarities and differences.

It is commonly assumed that older and younger adults have very different attitudes about seeking mental health services and that this is a major factor in reducing the use of mental health services by the elderly. However, little evidence exists to illustrate how elders actually perceive mental health care. Responses from a survey of 474 older adults age 65 and over were compared with data from a national survey of 1001 persons age 21-65. Results indicate similarities in many attitudes including likelihood of seeking treatment for severe mental disorders, importance of mental health care, and concerns about cost and coverage as barriers to care. Differences included use of services, perceptions about less severe disorders, referral sources, and preferred providers. Clinical, policy and public education implications are discussed.

Human service reorganization and its effects: a preliminary assessment of Florida's services integration 'experiment.'.

The present discussion reports on some of the first statewide data gathering and analysis to assess the consequences of the 1975 reorganization of the Florida Department of Health and Rehabilitative Services. Two major concepts guiding the reorganization were: (1) integration of services in order to cover more adequately the needs of clients, including "multi-problem" clients, and (2) decentralization of administrative authority of all programs under a single, district-wide management structure. Despite widespread interest in the Florida system, and two previous studies, no systematic, detailed study of the impact of reorganization at the service delivery level has been conducted until now. The results of this study indicate that departmental employees perceive substantial decentralization of authority and progress toward integration of services since the 1975 reorganization. Perceived improvement in client services is also indicated. Major factors cited as influential in the change are the move toward collocation of services, the establishment of administratively interlinked service networks, and to a lesser extent, the development of generalist managers.

Removal of status offenders from the juvenile justice system: the Florida experience.

In 1975 Florida transferred jurisdiction over runaway, truant or ungovernable children from the juvenile justice system to the child welfare system. This paper reports on the results of decriminalization.