Efficacy of lasers and light sources in long-term hair reduction: a systematic review.

Laser and light-based devices provide scope for long-term "hair-removal" however, there is limited evidence supporting their long-term efficacy. This study aimed to assess the long-term efficacy of laser and light-based "hair-removal" devices, taking into account variations in body site-specific variations in hair growthcycles. A systematic review of randomized controlled trials (RCTs) with follow-up periods greater than or equal to the length of one complete hair growth cycle in the body site targeted was conducted. Only five eligible RCTs were identified as suitable for inclusion, and these comprised a total of 223 patients. The average long-term hair reduction reported for neodymium:yttrium-aluminum-garnet (Nd:YAG) laser ranged from 30 to 73.61%, Alexandrite laser ranged from 35 to 84.25%, and Diode laser ranged from 32.5 to 69.2%. In all three devices, the greatest long-term reduction was observed from trials targeting leg hair (1-year growth cycle) and lowest from targeting facial hair (6-month growth cycle). Intense pulsed light (IPL) produced average long-term hair reduction of 52.7-27%; smallest reduction was observed from targeting the face area and greatest from targeting the axillary area (7-month growth cycle). In conclusion, greater long-term hair reduction was observed on body sites with longer hair growth cycles. Future trials should take into account the variation of hair growth cycles across body sites to provide accurate long-term data on treatment outcomes.

Poliosis circumscripta unmasking a scalp melanoma.

A 28-year-old man presented with a 1-year history of a localized patch of grey hair and an underlying darkly pigmented lesion on his right occipital area. Clinical appearance revealed poliosis overlying an asymmetrical plaque with variable degrees of brown pigmentation and white discolouration. Owing to the suspicious nature of the lesion, excision with a 2 mm margin was performed. Histology revealed an invasive melanoma with extensive regression and prominent involvement of multiple hair follicles. Scalp melanoma with associated poliosis is extremely rare, and has only been reported once in the literature to date. There have been two reports in the opthalmology literature regarding eyelash poliosis associated with orbital melanoma. The pathogenesis of poliosis still remains unclear. This is the second reported case of poliosis circmscripta unmasking a scalp melanoma, and highlights the importance of being vigilant when examining patients with poliosis of the scalp.

Predominance of activated, clonally expanded T helper type 17 cells within the CD4+ T cell population in psoriatic lesions.

Recent evidence points to the T helper type 17 (Th17) subset as key in the pathogenesis of psoriasis, but cells of this type in lesions remain to be fully characterized. Here we isolated, enumerated, functionally tested and clonotyped the CD4(+) Th cell population ex vivo from lesional biopsies and paired peripheral blood samples from psoriasis patients. Th17 cells were over-represented dramatically in lesions from all patients, representing 49-93% of CD4(+) Th cells compared with 3-18% in blood. Most lesional Th17 cells produced interleukin (IL)-17A ex vivo without further stimulation and expressed the CD45RO(+) phenotype characteristic of activated or memory cells. There was no increase in 'natural' [CD25(hi) forkhead box protein 3 (FoxP3(+))] regulatory T cells in lesions versus peripheral blood, but there was enrichment of 'induced' IL-10(+) regulatory T cell numbers in biopsies from some patients. The lesional Th17 cells exhibited a bias in T cell receptor Vß chain usage, suggestive of specific expansion by antigen. The therapeutic challenge is to overcome the dominance of overwhelming numbers of such antigen-specific Th17 cells in psoriatic lesions.

Systematic review of dermoscopy and digital dermoscopy/ artificial intelligence for the diagnosis of melanoma.

BACKGROUND: Dermoscopy improves diagnostic accuracy of the unaided eye for melanoma, and digital dermoscopy with artificial intelligence or computer diagnosis has also been shown useful for the diagnosis of melanoma. At present there is no clear evidence regarding the diagnostic accuracy of dermoscopy compared with artificial intelligence. OBJECTIVES: To evaluate the diagnostic accuracy of dermoscopy and digital dermoscopy/artificial intelligence for melanoma diagnosis and to compare the diagnostic accuracy of the different dermoscopic algorithms with each other and with digital dermoscopy/artificial intelligence for the detection of melanoma. METHODS: A literature search on dermoscopy and digital dermoscopy/artificial intelligence for melanoma diagnosis was performed using several databases. Titles and abstracts of the retrieved articles were screened using a literature evaluation form. A quality assessment form was developed to assess the quality of the included studies. Heterogeneity among the studies was assessed. Pooled data were analysed using meta-analytical methods and comparisons between different algorithms were performed. RESULTS: Of 765 articles retrieved, 30 studies were eligible for meta-analysis. Pooled sensitivity for artificial intelligence was slightly higher than for dermoscopy (91% vs. 88%; P = 0.076). Pooled specificity for dermoscopy was significantly better than artificial intelligence (86% vs. 79%; P < 0.001). Pooled diagnostic odds ratio was 51.5 for dermoscopy and 57.8 for artificial intelligence, which were not significantly different (P = 0.783). There were no significance differences in diagnostic odds ratio among the different dermoscopic diagnostic algorithms. CONCLUSIONS: Dermoscopy and artificial intelligence performed equally well for diagnosis of melanocytic skin lesions. There was no significant difference in the diagnostic performance of various dermoscopy algorithms. The three-point checklist, the seven-point checklist and Menzies score had better diagnostic odds ratios than the others; however, these results need to be confirmed by a large-scale high-quality population-based study.

Three RNA polymerase II carboxyl-terminal domain kinases display distinct substrate preferences.

CDK7, CDK8, and CDK9 are cyclin-dependent kinases (CDKs) that phosphorylate the C-terminal domain (CTD) of RNA polymerase II. They have distinct functions in transcription. Because the three CDKs target only serine 5 in the heptad repeat of model CTD substrates containing various numbers of repeats, we tested the hypothesis that the kinases differ in their ability to phosphorylate CTD heptad arrays. Our data show that the kinases display different preferences for phosphorylating individual heptads in a synthetic CTD substrate containing three heptamer repeats and specific regions of the CTD in glutathione S-transferase fusion proteins. They also exhibit differences in their ability to phosphorylate a synthetic CTD peptide that contains Ser-2-PO(4). This phosphorylated peptide is a poor substrate for CDK9 complexes. CDK8 and CDK9 complexes, bound to viral activators E1A and Tat, respectively, target only serine 5 for phosphorylation in the CTD peptides, and binding to the viral activators does not change the substrate preference of these kinases. These results imply that the display of different CTD heptads during transcription, as well as their phosphorylation state, can affect their phosphorylation by the different transcription-associated CDKs.

Identification and molecular cloning of a neuropeptide Y homolog that produces prolonged inhibition in Aplysia neurons.

The neuroendocrine bag cell neurons of the marine mollusk Aplysia produce prolonged inhibition that lasts for more than 2 hr. We purified a peptide from the abdominal ganglion that mimics this inhibition. Mass spectrometry and microsequence analysis indicate that the peptide is 40 aa long and is amidated at its carboxyl terminus. It is highly homologous to vertebrate neuropeptide Y (NPY) and other members of the pancreatic polypeptide family. As determined from cloned cDNA, the gene coding for the precursor protein shares a common structural organization with genes encoding precursors of the vertebrate family. The peptides may therefore have arisen from a common ancestral gene. Bag cell neurons are immunoreactive for Aplysia NPY, and Northern blot analysis indicates that as with its vertebrate counterparts, the peptide is abundantly expressed in the CNS. This suggests that peptides related to NPY may have important functions in the nervous system of Aplysia as well as in other invertebrates.

Isolation and partial characterization of neuropeptides that mimic prolonged inhibition produced by bag cell neurons in Aplysia.

The bag cell neurons of the marine mollusk Aplysia are part of a neural system that utilizes four neuropeptides as neurotransmitters. The peptides, derived from the egg-laying hormone/bag cell peptide (ELH/BCP) precursor protein, are released during a 20-min burst discharge of the bag cells and produce several types of responses in various abdominal ganglion neurons. In the identified neurons L3 and L6, bag cell activity produces prolonged inhibition that lasts for more than 2 h. One of the bag cell peptides, alpha-BCP, mediates an early component of the inhibition in these neurons. To identify the co-transmitter mediating the prolonged component of inhibition, we purified material from an acid extract of abdominal ganglia using molecular sizing high-pressure liquid chromatography (HPLC) on TSK 250-125 followed by two steps of reverse-phase HPLC on C4 or C18. We isolated three inhibitory factors that mimic the prolonged component of inhibition. Mass spectroscopy and partial amino acid sequence analysis indicate one factor is ELH [2-36], that is, ELH that lacks the first, N-terminal amino acid. This inhibitory activity was similar in potency to that of ELH and is the first to be described for an ELH-related peptide. The two other factors were approximately 3,300 and 4,700 Da and were effective at 10- and 50-fold lower concentration, respectively, than ELH or its fragment. Amino acid composition analysis suggests that they are not derived from the ELH/BCP precursor protein. The 4,700 Da factor is effective at the lowest concentration and produces an effect that lasts as long as 100 min.(ABSTRACT TRUNCATED AT 250 WORDS)

The membrane glycoprotein Ia-IIa (VLA-2) complex mediates the Mg++-dependent adhesion of platelets to collagen.

We have purified the platelet membrane glycoprotein Ia-IIa complex by detergent solubilization and sequential affinity chromatography on Concanavalin A-Sepharose and collagen-Sepharose. The complex, which is identical to the VLA-2 complex of lymphocytes and other cells and contains subunits of 160 and 130 kD on SDS-PAGE, was labeled with 125I and incorporated into phosphatidyl choline liposomes. The liposomes, like intact platelets, adhered to collagenous substrates in an Mg++-dependent manner with a K'a(Mg++) of 3.5 mM. Little adhesion of the liposomes to collagen occurred when Mg++ was replaced by Ca++ or EDTA. Calcium ions inhibited the Mg++-dependent adhesion with a K'i(Ca++) of 5.5 mM. Liposomes containing the Ia-IIa complex adhered to substrates composed of types I, II, III, and IV collagen, but did not effectively adhere to substrates composed of type V collagen or gelatin. Adhesion to collagen was specific. The liposomes did not adhere to fibronectin, vitronectin, laminin, thrombospondin, fibrinogen, or von Willebrand factor substrates. The monoclonal antibody P1H5, which specifically immunoprecipitated the Ia-IIa complex, also specifically inhibited the Mg++-dependent adhesion of both platelets and Ia-IIa-containing liposomes to collagen substrates. These findings provide additional evidence that the platelet membrane Ia-IIa complex is the mediator of Mg++-dependent platelet adhesion to collagen and suggest that the VLA-2 complex may also function as an Mg++-dependent collagen receptor in other cells.

Isolation and characterization of a platelet surface collagen binding complex related to VLA-2.

A heterodimeric, Mg++-dependent, collagen binding protein has been isolated from platelet membranes. Electrophoretic properties and monoclonal antibody reactivity indicate that the heavy chain of the complex is platelet membrane glycoprotein Ia and that the light chain is glycoprotein IIa. Furthermore, the receptor appears to be identical with the recently defined VLA-2 complex found on activated T-lymphocytes, platelets and other cells. When incorporated into liposomes, the purified complex mediates the Mg++-dependent adhesion of the liposomes to collagen substrates. These observations suggest that the VLA-2 complex mediates cellular adhesion to collagen in platelets and possibly in other cells.