A systematic review of occupational therapy intervention for handwriting skills in 4-6 year old children.

INTRODUCTION: Handwriting skills play a significant role in all stages of an individual's life. Writing interventions should be considered at a younger age to ensure proper development of writing skills. Hence, the aims of this study is to evaluate the current evidence of occupational therapy interventions in handwriting skills for 4-6 year old children. METHODS: Published literature was systematically searched according to PRISMA guidelines using specific key terms. Initial search identified 785 studies; however only seven met the inclusion criteria and were assessed for final review. Studies were methodologically appraised using the McMaster Critical Review Form-Quantitative Studies. RESULTS: The review found no randomised control trial study design pertaining to the reviewed area. However, it can be seen that occupational therapy interventions for writing skills in 4-6 year old children managed to increase the targeted skills. The results were similar across samples with or without disabilities. An effective integration of occupational therapy interventions into educational curriculum was found to save both time and cost. CONCLUSION: The long-term benefit from these interventions and the effects of these interventions on a broader spectrum of fine motor abilities need to be explored further with stronger research designs. However, the lack of studies adopting high level study designs, i.e., RCT designs means, results need to be approached with caution by occupational therapists when implementing handwriting skills intervention in practice.

Genetic Characteristics of Polycythemia Vera and Essential Thrombocythemia in Korean Patients.

BACKGROUND: Despite recent advances in the investigation of myeloproliferative neoplasms (MPN), the impact of genetic heterogeneity on its molecular pathogenesis has not been fully elucidated. Thus, in this study, we aim to characterize the genetic complexity in Korean patients with polycythemia vera (PV) and essential thrombocythemia (ET). METHODS: We conducted association studies using 84 single-nucleotide polymorphisms (SNPs) in 229 patients (96 with PV and 133 with ET) and 170 controls. Further, whole-genome sequencing was performed in six patients (two with JAK2 V617F and four with wild-type JAK2), and putative somatic mutations were validated in a further 69 ET patients. Clinical and laboratory characteristics were also analyzed. RESULTS: Several germline SNPs and the 46 haplotype were significantly associated with PV and ET. Three somatic mutations in MPDZ, IQCH, and CALR genes were selected and validated. The frequency of the CALR mutation was 58.0% (40/69) in ET patients, who did not carry JAK2/MPL mutations. Moreover, compared with JAK2 V617F-positive patients, those with CALR mutations showed lower hemoglobin and hematocrit levels (P = 0.004 and P = 0.002, respectively), higher platelet counts (P =0.008), and a lower frequency of cytoreductive therapy (P = 0.014). CONCLUSION: This study was the first comprehensive investigation of the genetic characteristics of Korean patients with PV and ET. We found that somatic mutations and the 46 haplotype contribute to PV and ET pathogenesis in Korean patients.

A randomized bilateral vehicle-controlled study of eflornithine cream combined with laser treatment versus laser treatment alone for facial hirsutism in women.

BACKGROUND AND OBJECTIVE: Although there are a multitude of therapeutic modalities for removing unwanted facial hair in women, there is very little information on using the newer medical treatment approaches in combination. This study was designed to determine whether topical eflornithine can enhance the efficacy of laser hair removal. DESIGN: This was a randomized, double-blind, placebo-controlled, right-left comparison study of eflornithine cream combined with laser treatment versus laser alone for treating unwanted hair on the upper lip in women. All subjects underwent treatment to the entire upper lip with a long pulse alexandrite laser (10-40 ms pulse duration) at fluences of 7 to 40 J/cm(2). Laser treatments were performed every 4 weeks for up to 6 sessions. Each patient also applied either eflornithine or placebo cream twice daily to each side of the upper lip in a double-blinded manner. Subjects were evaluated for safety by recording adverse events and for efficacy via (1) investigator global scoring, (2) patient self assessment, and (3) hair count analysis. RESULTS: Both treatment modalities were well tolerated by the 31 evaluable patients. All 3 outcome measures showed significantly better results in favor of eflornithine plus laser versus laser treatment alone. At the end of the study, complete or almost complete hair removal was achieved in 29 of 31 (93.5%) of the eflornithine-laser-treated sites versus 21 of 31 (67.9%) for the placebo cream-laser-treated sites (P = .021, McNemar test). Statistically significant differences in favor of eflornithine were likewise demonstrated at the final assessment through blinded patient grading (13/31 patients [41.9%] thought that the eflornithine was superior to placebo, P = .029, Poisson regression) and hair count analysis (P < .01, paired t test). LIMITATIONS: This is a single-center study that did not determine whether the differences noted above last beyond 6 months. CONCLUSIONS: On the basis of both investigator and patient assessments and hair count analysis, we have demonstrated that the addition of eflornithine to laser hair removal results in a more rapid and complete reduction of unwanted facial hair in women when the combination is used for up to 6 months.

Cutaneous melanin exhibiting fluorescence emission under near-infrared light excitation.

Under ultraviolet and visible light excitation, melanin is essentially a nonfluorescent substance. This work reports our study on near-infrared (NIR) fluorescence properties of melanins, and explores potential applications of NIR fluorescence techniques for evaluating skin disorders involving melanin. The NIR fluorescence spectrum is obtained using a fiber optic NIR spectrometer under 785-nm laser excitation. In vitro measurements are performed on synthetic dihydroxyphenylalanine (DOPA) melanin, melanin extracted from Sepia ink sacs, human hair, animal fur, and bird feathers. Paired spectral comparisons of white and black skin appendages show that melanization of hair, fur, or feathers more than doubles the NIR fluorescence. In vivo NIR autofluorescence of normal dorsal and volar forearm skin of 52 volunteers is measured. Dorsal forearm skin, which is darker than volar skin, exhibits significantly greater NIR fluorescence. Patients with vitiligo (n=4), compound nevus (n=3), nevus of Ota (n=1), superficial spreading melanoma (n=3), and postinflammatory hyperpigmentation (n=1) are also evaluated. NIR fluorescence is greater within the lesion than the surrounding normal skin for all these conditions except vitiligo, where the converse was true. The observed melanin NIR fluorescence provides a new approach to in vitro and in vivo melanin detection and quantification that may be particularly useful for evaluating pigmented skin lesions.

Selective depletion of human DNA-methyltransferase DNMT1 proteins by sulfonate-derived methylating agents.

5-Methylcytosine residues in the DNA (DNA methylation) are formed from the transfer of the methyl group from S-adenosylmethionine to the C-5 position of cytosine by the DNA-(cytosine-5) methyltransferases (DNMTs). Although regional hypermethylation and global hypomethylation of the genome are commonly observed in neoplastic cells, how these aberrant methylation patterns occur remains unestablished. We report here that sulfonate-derived methylating agents, unlike N-methylnitrosourea or iodomethane, are potent in depleting DNMT1 proteins in human cells, in addition to their DNA-damaging properties. Their effects on cellular DNMT1 are time and dosage dependent but independent of cell type. Unlike gamma-irradiation, these agents apparently do not activate the p53/p21(WAF1) DNA damage response pathway to deplete the DNMT1 proteins because cells with wild-type, mutated, or inactivated p53 behave similarly. However, cell cycle analysis and protease assay studies strongly suggest that methylmethanesulfonate may activate a cellular protease to degrade DNMT1. These results explain why reported observations on the effect of alkylating agents on DNMT1 activities in human cells vary significantly and provide a crucial link to understand the mechanism behind genomic hypomethylation.

Update on primary cicatricial alopecias.

UNLABELLED: The cicatricial alopecias encompass a diverse group of disorders characterized by permanent destruction of the hair follicle and irreversible hair loss. Destruction of the hair follicle can result from primary, folliculocentric disease or as a secondary result. This article focuses on the former, or primary cicatricial alopecias. The cause and pathogenesis of many of these disorders are largely unknown. Although unique clinicopathologic features allow for accurate diagnosis in some cases, diagnostic certainty is often elusive and reflects the limits of present understanding. Classification of the primary cicatricial alopecias on the basis of pathology provides a diagnostic and investigational framework and, it is hoped, will facilitate future enlightenment. Details of classification, etiopathogenesis, clinicopathologic features, differential diagnosis, and practical management of the primary cicatricial alopecias will be discussed. LEARNING OBJECTIVES: Upon completion of this learning activity, participants should be familiar with the following aspects of the primary cicatricial alopecias: (1) the new, consensus-issued classification scheme, (2) current understanding about etiopathogenesis, (3) salient clinicopathologic features, (4) differential diagnosis, and (5) therapeutic management.

Treatment of Kimura's disease with cyclosporine.

Kimura's disease is a rare, chronic inflammatory disease of unknown cause. It is characterized by painless subcutaneous swellings and lymphadenopathy, commonly affecting the head and neck region. This is associated with peripheral blood eosinophilia and raised serum IgE. It has distinct histological features of lymphoid follicles, eosinophilic infiltrate, fibrosis and vascular proliferation. The disease usually has a benign, indolent course. Traditionally, therapeutic options have included surgery, radiotherapy and steroids but response has been less than satisfactory. Recently, cyclosporine has been reported to be effective in the treatment of Kimura's disease. In this article, we present a middle-aged Chinese female with Kimura's disease for 20 years and her favourable response to cyclosporine.

Derivation of functional insulin-producing cell lines from primary mouse embryo culture.

We have previously described the derivation of insulin-producing cell lines from mouse embryonic stem cells (mESCs) by differentiation of an intermediate lineage-restricted E-RoSH cell line through nutrient depletion in the presence of nicotinamide followed by limiting dilution. Here we investigated whether insulin-producing cell lines could be similarly derived directly from mouse embryo cells or tissues. Using a similar approach, we generated the RoSH2.K and MEPI-1 to -14 insulin-producing cell lines from the 5.5-dpc embryo-derived E-RoSH-analogous RoSH2 cell line and a 6.0-dpc mouse embryo culture, respectively. Insulin content was approximately 8 microg/10(6) MEPI-1 cells and 0.5 microg/10(6) RoSH2.K cells. Like insulin-producing mESC-derived ERoSHK cell lines, both MEPI and RoSH2.K lines were amenable to repeated cycles of freeze and thaw, replicated for months with a doubling time of 3-4 days, and exhibited genomic, structural, biochemical, and pharmacological properties of pancreatic beta-cells, including storage and release of insulin and C-peptide in an equimolar ratio. Transplantation of these cells also reversed hyperglycemia in streptozotocin-treated SCID mice and did not induce teratoma. Like ERoSHK cells, both RoSH2.K and MEPI-1 cells also induced hypoglycemia in the mice. Therefore, our protocol is robust and could reproducibly generate insulin-producing cell lines from different embryonic cell sources.

Generating mESC-derived insulin-producing cell lines through an intermediate lineage-restricted progenitor line.

Generating surrogate insulin-producing cells from embryonic stem cells (ESCs) through in vitro replication of successive steps during pancreatic development has been challenging . Here we describe a novel reproducible protocol to establish homogeneous and scalable insulin-producing cell lines from mouse (m) ESCs via differentiation of the previously described lineage-restricted clonal mESC-derived E-RoSH cells. Unlike their parental mESCs, E-RoSH cells expressed high levels of mesodermal and endodermal genes. Nutrient depletion in the presence of nicotinamide inhibited proliferation of E-RoSH cells and induced differentiation into heterogeneous cultures comprising vascular-like structures that produced detectable levels of insulin and C-peptide in an equimolar ratio. Limiting dilution of these cultures resulted in the isolation of eight independent insulin-producing cell lines in five experiments. All these lines were cloned and shown to be amenable to repeated cycles of freeze and thaw and to replicate for months with a doubling time of 3-4 days. Under such conditions, the cultured cells exhibited genomic, structural, biochemical, and pharmacological properties of pancreatic beta cells, including storage of an equimolar ratio of insulin and C-peptide in granules and release of the contents of these organelles through a glucose-sensitive machinery. After transplantation, these cells reversed hyperglycemia in streptozotocin-treated SCID mice and did not form teratomas.

Photodynamic therapy with 20% aminolevulinic acid for the treatment of recalcitrant viral warts in an Asian population.

BACKGROUND: Topical photodynamic therapy (PDT) is based on the principle of targeted tissue destruction using selective photosensitization via a topical porphyrin precursor, followed by light exposure. It is well established for the treatment of actinic keratoses and superficial nonmelanoma skin cancers. Some studies have reported good efficacy when using PDT to treat viral warts in the Western population. METHODS: We carried out a prospective, single-arm, phase II study of 5-aminolevulinic acid (5-ALA)-PDT in the treatment of recalcitrant viral warts in an Asian population. Recalcitrant viral warts were surgically pared, and then treated with 20% 5-ALA cream (Medac, Hamburg, Germany) under occlusion for 4 hours before irradiation with a red light source (Waldmann PDT1200; wavelength, 590-700 nm) at an irradiance of 50 mW/cm(2) and a total dose of 50 J/cm(2). PDT was repeated fortnightly for a maximum of four times. RESULTS: Twelve adult Asian patients were enrolled into the study (10 males, two females). The mean age of the patients was 32.8 years (range, 18-70 years). They had skin phototypes III-IV. Nine patients had plantar warts and three patients had hand warts (two had warts on the fingers, one had a wart on the palm). Five patients (42%) showed complete disappearance of their warts, one patient (8%) showed partial clearance (greater than 50% decrease in the wart area), five patients (42%) had stable disease (less than 50% decrease in the wart area), and one (8%) showed progressive disease (increase in the wart area). Adverse effects included mild to moderate pain and erythema, which lasted no longer than 48 hours and was well tolerated by all patients. None of the patients withdrew from the study because of side-effects. CONCLUSION: 5-ALA-PDT, given its noninvasiveness, minimal adverse effects, and good cosmetic results, is a promising alternative treatment for recalcitrant viral warts. Further studies with a larger cohort of patients would be of value.

Elucidating the secretion proteome of human embryonic stem cell-derived mesenchymal stem cells.

Transplantation of mesenchymal stem cells (MSCs) has been used to treat a wide range of diseases, and the mechanism of action is postulated to be mediated by either differentiation into functional reparative cells that replace injured tissues or secretion of paracrine factors that promote tissue repair. To complement earlier studies that identified some of the paracrine factors, we profiled the paracrine proteome to better assess the relevance of MSC paracrine factors to the wide spectrum of MSC-mediated therapeutic effects. To evaluate the therapeutic potential of the MSC paracrine proteome, a chemically defined serum-free culture medium was conditioned by MSCs derived from human embryonic stem cells using a clinically compliant protocol. The conditioned medium was analyzed by multidimensional protein identification technology and cytokine antibody array analysis and revealed the presence of 201 unique gene products. 86-88% of these gene products had detectable transcript levels by microarray or quantitative RT-PCR assays. Computational analysis predicted that these gene products will significantly drive three major groups of biological processes: metabolism, defense response, and tissue differentiation including vascularization, hematopoiesis, and skeletal development. It also predicted that the 201 gene products activate important signaling pathways in cardiovascular biology, bone development, and hematopoiesis such as Jak-STAT, MAPK, Toll-like receptor, transforming growth factor-beta, and mTOR (mammalian target of rapamycin) signaling pathways. This study identified a large number of MSC secretory products that have the potential to act as paracrine modulators of tissue repair and replacement in diseases of the cardiovascular, hematopoietic, and skeletal tissues. Moreover our results suggest that human embryonic stem cell-derived MSC-conditioned medium has the potency to treat a variety of diseases in humans without cell transplantation.

Derivation of clinically compliant MSCs from CD105+, CD24- differentiated human ESCs.

Adult tissue-derived mesenchymal stem cells (MSCs) have demonstrated therapeutic efficacy in treating diseases or repairing damaged tissues through mechanisms thought to be mediated by either cell replacement or secretion of paracrine factors. Characterized, self-renewing human ESCs could potentially be an invariable source of consistently uniform MSCs for therapeutic applications. Here we describe a clinically relevant and reproducible manner of generating identical batches of hESC-derived MSC (hESC-MSC) cultures that circumvents exposure to virus, mouse cells, or serum. Trypsinization and propagation of HuES9 or H1 hESCs in feeder- and serum-free selection media generated three polyclonal, karyotypically stable, and phenotypically MSC-like cultures that do not express pluripotency-associated markers but displayed MSC-like surface antigens and gene expression profile. They differentiate into adipocytes, osteocytes, and chondrocytes in vitro. Gene expression and fluorescence-activated cell sorter analysis identified CD105 and CD24 as highly expressed antigens on hESC-MSCs and hESCs, respectively. CD105+, CD24- monoclonal isolates have a typical MSC gene expression profiles and were identical to each other with a highly correlated gene expression profile (r(2) > .90). We have developed a protocol to reproducibly generate clinically compliant and identical hESC-MSC cultures.

Non-ablative 1,450-nm diode laser treatment of striae distensae.

BACKGROUND AND OBJECTIVES: Striae distensae are dermal scars with flattening and atrophy of the epidermis. Successful treatment of these stretch marks has been disappointing. The non-ablative 1,450-nm diode laser has been shown to improve atrophic scars and may be expected to improve striae. As yet, no study has been published to document the effects of this laser on striae. Our aim is to evaluate the efficacy of the 1,450-nm diode laser in the treatment of striae rubra and striae alba in Asian patients with skin types 4-6. STUDY DESIGN/MATERIALS AND METHODS: Striae on one half of the body in 11 patients were treated with the 1,450-nm diode laser with cryogen cooling spray with the other half serving as a control. The following parameters were used: 6 mm spot size and dynamic cooling device (DCD) for 40 milliseconds to protect the epidermis. Patients were randomly assigned to receive either 4, 8, or 12 J/cm2. A total of three treatments were given at 6-week intervals. The following sites were treated: abdomen, arms, back, buttocks, and thighs. Two patients had striae rubra and nine striae alba. Clinical photographs were taken before and after each treatment and analysis was undertaken through photographic evaluation by non-treating physicians. RESULTS: At 2 months after the last treatment, no patients showed any noticeable improvement in the striae on the treated side compared to baseline and to the control areas. Side effects were limited to transient erythema and postinflammatory hyperpigmentation (PIH), which occurred in seven (64%) patients. CONCLUSIONS: The non-ablative 1,450-nm diode laser is not useful in the treatment of striae in patients with skin types 4, 5, and 6.

Establishing clonal cell lines with endothelial-like potential from CD9(hi), SSEA-1(-) cells in embryonic stem cell-derived embryoid bodies.

BACKGROUND: Differentiation of embryonic stem cells (ESCs) into specific cell types with minimal risk of teratoma formation could be efficiently directed by first reducing the differentiation potential of ESCs through the generation of clonal, self-renewing lineage-restricted stem cell lines. Efforts to isolate these stem cells are, however, mired in an impasse where the lack of purified lineage-restricted stem cells has hindered the identification of defining markers for these rare stem cells and, in turn, their isolation. METHODOLOGY/PRINCIPAL FINDINGS: We describe here a method for the isolation of clonal lineage-restricted cell lines with endothelial potential from ESCs through a combination of empirical and rational evidence-based methods. Using an empirical protocol that we have previously developed to generate embryo-derived RoSH lines with endothelial potential, we first generated E-RoSH lines from mouse ESC-derived embryoid bodies (EBs). Despite originating from different mouse strains, RoSH and E- RoSH lines have similar gene expression profiles (r(2) = 0.93) while that between E-RoSH and ESCs was 0.83. In silico gene expression analysis predicted that like RoSH cells, E-RoSH cells have an increased propensity to differentiate into vasculature. Unlike their parental ESCs, E-RoSH cells did not form teratomas and differentiate efficiently into endothelial-like cells in vivo and in vitro. Gene expression and FACS analysis revealed that RoSH and E-RoSH cells are CD9(hi), SSEA-1(-) while ESCs are CD9(lo), SSEA-1(+). Isolation of CD9(hi), SSEA-1(-) cells that constituted 1%-10% of EB-derived cultures generated an E-RoSH-like culture with an identical E-RoSH-like gene expression profile (r(2) = 0.95) and a propensity to differentiate into endothelial-like cells. CONCLUSIONS: By combining empirical and rational evidence-based methods, we identified definitive selectable surface antigens for the isolation and propagation of lineage-restricted stem cells with endothelial-like potential from mouse ESCs.

A clinical study of childhood alopecia areata in Singapore.

Alopecia areata (AA) is a common cause of nonscarring alopecia. The aim of this epidemiologic study is to review the clinical characteristics and treatment of childhood alopecia areata in a mixed ethnic population. The study population consisted of a total of 392 children seen over a 4-year period with AA diagnosed before the age of 16 years. The female:male ratio was 1:1.4. There were 309 Chinese (78.8%), 51 Malays (13.0%), and 32 Indians (8.2%). The mean age at the time of diagnosis was 11.2 years. The majority of patients (71.7%) had alopecia of less than 6-months duration and 6% had previous episodes of AA. Females appeared to have more severe involvement. A familial history of AA was observed in 33 patients (8.4%). Associated atopy was found in 26.6% of patients and in 32.3% of their first-degree relatives. Other associations such as vitiligo or Down syndrome were rare. For limited AA, topical and/or intralesional corticosteroid was the first-line treatment used and squaric acid dibutyl ester was the choice of treatment for patients with extensive involvement. The profile of the poor respondents to therapy included young age of onset, past history of AA, Down syndrome, and extensive involvement.

Temporal triangular alopecia: report of five cases in Asian children.

Temporal triangular alopecia (TTA) is a nonscarring alopecia first described in 1905. We report five cases of TTA in Asian children and review the literature.

Primary cicatricial alopecias: clinicopathology of 112 cases.

BACKGROUND: Cicatricial alopecias represent a diverse group of diseases characterized by a lack of follicular ostia and irreversible alopecia. There is limited literature on the epidemiology and therapeutics of cicatricial alopecias. OBJECTIVE: The aim of this study was to review the epidemiology, clinical characteristics, and treatment of inflammatory cicatricial alopecias in a mixed ethnic population referred to a university hair clinic. METHODS: The study population consisted of 112 patients seen during a 5-year period with acquired primary cicatricial alopecias. This represented 3.2% of the total number of trichologic consultations seen at the University of British Columbia Hair Clinic, Vancouver, British Columbia, Canada. RESULTS: The ratio of lymphocytic to neutrophilic cicatricial alopecias was 4:1. Lymphocytic cicatricial alopecias had a tendency to affect middle-aged women, whereas neutrophilic cicatricial alopecias had a predilection for middle-aged men. CONCLUSIONS: An accurate diagnosis of cicatricial alopecia is achieved through careful clinicopathologic evaluation. We suggest that a scalp biopsy is mandatory in all cases. Multiple biopsies may be necessary for some affected individuals to achieve a definitive diagnosis as a result of a highly variable clinical course. An aggressive multiple modality therapeutic approach is often necessary to prevent further irreversible follicular destruction, implying cicatrical alopecia should be considered a trichologic emergency. Current therapeutic options for lymphocytic cicatricial alopecia include corticosteroids, antimalarials, and isotretinoin versus antibiotics, corticosteroids, and isotretinoin for neutrophilic cicatricial alopecias.

Cutaneous mucinosis in dermatomyositis associated with a malignant tumor.

We report a case of dermatomyositis presenting with cutaneous mucinosis as the sole manifestation. A malignancy screen revealed an underlying nasopharyngeal carcinoma.

Eosinophilic pustular folliculitis (Ofuji's disease) in Singapore: a review of 23 adult cases.

The case records of 23 patients with classic eosinophilic pustular folliculitis (EPF), or Ofuji's disease, seen at the National Skin Centre in Singapore, from 1990 to 2001 were reviewed. All patients had clinical and histopathological findings consistent with EPF. There were eight men and 15 women (ratio 1:1.6). The mean age at presentation was 35 years. There was a marked predilection for Chinese patients (87%), with a racial distribution of 20:2:1 of Chinese, Malay and Indian patients, respectively. The most frequent site of occurrence was the face, particularly over both cheeks. The majority of patients (90%) treated with oral indomethacin had a good response within 2-4 weeks. Relapses were frequent in 82.6% of patients and maintenance with indomethacin or ketoprofen was beneficial. Eosinophilic pustular folliculitis is a rare but important disease entity presenting with recurrent indurated erythematous papulopustules and plaques on the face. Increased awareness of this condition is important as it can mimic many other conditions presenting as red plaques on the face.