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IFN regulatory factor 8 (IRF8) is a key transcription factor for myeloid cell differentiation and its expression is frequently lost in hematopoietic cells of human myeloid leukemia patients. IRF8-deficient mice exhibit uncontrolled clonal expansion of undifferentiated myeloid cells that can progress to a fatal blast crisis, thereby resembling human chronic myelogeneous leukemia (CML). Therefore, IRF8 is a myeloid leukemia suppressor. Whereas the understanding of IRF8 function in CML has recently improved, the molecular mechanisms underlying IRF8 function in CML are still largely unknown. In this study, we identified acid ceramidase (ACDase) as a general transcription target of IRF8. We demonstrated that IRF8 expression is regulated by IRF8 promoter DNA methylation in myeloid leukemia cells. Restoration of IRF8 expression repressed A-CDase expression, resulting in C16 ceramide accumulation and increased sensitivity of CML cells to FasL-induced apoptosis. In myeloid cells derived from IRF8-deficient mice, A-CDase protein level was dramatically increased. Furthermore, we demonstrated that IRF8 directly binds to the A-CDase promoter. At the functional level, inhibition of A-CDase activity, silencing A-CDase expression, or application of exogenous C16 ceramide sensitized CML cells to FasL-induced apoptosis, whereas overexpression of A-CDase decreased CML cells' sensitivity to FasL-induced apoptosis. Consequently, restoration of IRF8 expression suppressed CML development in vivo at least partially through a Fas-dependent mechanism. In summary, our findings determine the mechanism of IRF8 downregulation in CML cells and they determine a primary pathway of resistance to Fasmediated apoptosis and disease progression. Cancer Res; 71(8); 2882-91. Ó2011 AACR.

SUMMARYThe topic of vitamin D is at the forefront of discussions due to evidence suggesting its role in extra-skeletal health. It is already established that vitamin D plays a key role in skeletal health in young and elderly adults. This vitamin is obtained mainly through sunlight; various factors such as skin pigmentation and seasons affect cutaneous synthesis. Debates about the effects of sunscreen use on cutaneous synthesis of vitamin D have arisen in recent years. An updated review of the literature emphasizes that adequate levels of vitamin D are needed to prevent osteoporosis, falls and fractures in the elderly population. Emerging data also point to its role in cardiovascular disease, autoimmune conditions and cancers. Normal usage of sunscreen by adults has not shown to decrease cutaneous synthesis of vitamin D. Recommended Daily Allowance for vitamin D, released in 2010, was based on studies examining skeletal effects of this vitamin. Oral intake with vitamin D-enriched foods or vitamin D supplements is recommended over prolonged ultraviolet exposure to maintain proper serum levels. Patients should not be discouraged from normal usage of sunscreens due to their well-established photoprotective effects. 2014; 30: 137-145 In addition to the well-established effects of vitamin D on bone health, numerous studies have shown the association of vitamin D with extra-skeletal conditions, such as cardiovascular disease and several cancers (1). Since sun exposure is one of only three ways of obtaining vitamin D, a debate has ensued about the consequences of photoprotection, such as sun avoidance, the use of photo-protective clothing and hats, and the application of sunscreens, on serum 25-hydroxyvitamin-D (25(OH)D) levels. Serum levels of 25(OH)D reflect vitamin D status. The following review focuses on the recent evidence on the association between extra-skeletal benefits and serum 25(OH)D levels, the impact of photoprotection, and recommendations for managing vitamin D insufficiency and deficiency. Photodermatol Photoimmunol Photomed ROLE OF VITAMIN DThe benefits of vitamin D in skeletal health have been well-established in literature. Optimization of bone mass from infancy until adolescence forms the foundation for primary prevention of osteoporosis. In a survey of children with vitamin D deficiency, defined as serum 25(OH)D concentrations < 50 nmol/l, 71% of these children displayed rachitic changes on radiographic studies (2, 3). Additionally, vitamin D deficiency in adolescence can trigger osteoporosis and pathologic fractures in late adulthood. In fact, supplementation of vitamin D in the elderly decreases the risk of Photodermatology, Photoimmunology & Photomedicine

Background: Management of patients with cleft lip and palate (CLP) includes orthodontic treatment prior to bone grafting. Palatal expansion is done using slow or rapid palatal expansions (RPE). Controversy still exists regarding choice of expansion appliances used. This study was conducted to find out whether the Quad helix appliance represents a reasonable alternative to using conventional rapid maxillary expansion appliance among cleft lip and palate patients. Methods: Twenty cleft lip and palate patients had orthodontic study models taken prior to expansion and at the end of expansion. There pre and post treatment study models were analyzed for changes in intermolar width, molar tipping and molar rotation. Result: The difference in molar tipping, increase in intercanine and molar width between slow palatal expansion (SPE) and rapid palatal expansion (RPE) group was not statistically significant. A difference between the two groups was found in the ability to rotate molars. Conclusion: The clinical findings suggest that maxillary expansion using the Quad helix appliance represents a reasonable alternative to using conventional rapid maxillary expansion appliances among cleft patients. MJAFI 2009; 65 : 150-153

Apart from the typical onion skin appearance, PO shows various other radiographic appearances. The radiographic appearance of Periostitis Ossificans may reflect the duration, progression and the mode of healing of the disease process. The radiographic classification of PO depends on the type of radiographs taken for evaluation.

Recent studies have suggested that inflammatory responses may play an important role in the pathophysiology of depression. In fact, depressed individuals have been found to have higher levels of pro-inflammatory cytokines, especially tumor necrosis factor-alpha (TNF-α) and interleukin-6. This appears to be independent of any pre-existing chronic inflammatory disorders. In this article, various studies correlating increased levels of cytokines to depression are reviewed. As much as 60% of individuals with psoriasis also suffer from clinical depression. TNF-α antagonists, frequently used in the treatment of psoriasis, may be helpful in directly reducing depressive symptoms for patients with psoriasis and other chronic inflammatory conditions.

Congenital ichthyosiform erythroderma is an autosomal recessive ichthyosis characterized by severe scaling and erythroderma. We report a family of three siblings who were all born with a collodion membrane and presented with diffuse scaling and pruritus. All three children subsequently developed chronic cutaneous dermatophyte infections requiring oral antifungals. One child developed superinfection with methicillin-resistant Staphylococcus aureus requiring antibiotics.

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