Risk of skin cancer after ultraviolet phototherapy in patients with vitiligo: a systematic review and meta-analysis.

BACKGROUND: Although ultraviolet (UV) phototherapy is an effective treatment for vitiligo, its effect on the risk of skin cancer remains controversial. AIM: To investigate the association between UV phototherapy and skin cancer risk in patients with vitiligo. METHODS: A systematic review was performed for studies published before 5 May 2021 in the PubMed, Embase, Web of Science and Cochrane Library databases. The primary outcome was the association of UV phototherapy with the risk of skin cancer in patients with vitiligo. A meta-analysis with a random-effects model was conducted. RESULTS: Five retrospective cohort studies covering a total of 228 607 patients with vitiligo (110 038 who had been treated with UV phototherapy and 118 569 patients who had not) were included in the meta-analysis. The risk of nonmelanoma skin cancer [Mantel-Haenszel risk ratio (MHRR) = 0.95; 95% CI 0.44-2.05] and melanoma (MHRR = 1.11; 95% CI 0.33-3.82) did not significantly increase after phototherapy in patients with vitiligo. In the subgroup analysis, we also found no significant association between phototherapy with narrowband UVB phototherapy specifically and risk of skin cancer in patients with vitiligo. There was no significant difference in risk of skin cancer between patients from Europe and those from East Asia and the risk was not affected by the number of narrowband UVB phototherapy sessions. CONCLUSIONS: The findings of this systematic review and meta-analysis suggest that UV phototherapy is a safe treatment for vitiligo with no significant risk of skin cancer.

Birth month and risk of atopic dermatitis: a nationwide population-based study.

BACKGROUND: An individual's birth month has been associated with allergic diseases, but little is known about the association between birth month and atopic dermatitis (AD). OBJECTIVE: The aim of this study was to investigate the risk of AD in children born in various months. METHODS: Using Taiwan's National Health Insurance Research Database, we conducted a case-control study that included 31 237 AD cases and 124 948 age- and gender-matched controls without AD. Data regarding sociodemographic factors and coexisting medical conditions were collected and controlled in the multivariate logistic regression to determine the adjusted odds ratios and 95% confidence intervals for AD associated with the participant's birth month. RESULTS: Compared with people born in May, people born in December had the highest risk of AD (OR 1.17, 95% CI 1.10-1.25), followed by people born in October (OR 1.15, 95% CI 1.08-1.22) and November (OR 1.13, 95% CI 1.06-1.20). Low income (OR 1.28), asthma (OR 1.88), allergic rhinitis (OR 1.70), psoriasis (OR 2.36), vitiligo (OR 1.99), urticaria (OR 2.14), and systemic lupus erythematosus (OR 1.91) were significant coexisting medical conditions associated with AD. CONCLUSION: Being born in December, October, or November may be associated with an increased risk of AD. Future investigations are needed to evaluate the possible mechanism behind the association between birth month and AD.

Optical coupling from InGaAs subcell to InGaP subcell in InGaP/InGaAs/Ge multi-junction solar cells.

Spatially-resolved electroluminescence (EL) images in the triple-junction InGaP/InGaAs/Ge solar cell have been investigated to demonstrate the subcell coupling effect. Upon irradiating the infrared light with an energy below bandgap of the active layer in the top subcell, but above that in the middle subcell, the EL of the top subcell quenches. By analysis of EL intensity as a function of irradiation level, it is found that the coupled p-n junction structure and the photovoltaic effect are responsible for the observed EL quenching. With optical coupling and photoswitching effects in the multi-junction diode, a concept of infrared image sensors is proposed.

Prostanoid EP1 receptors mediate up-regulation of the orphan nuclear receptor Nurr1 by cAMP-independent activation of protein kinase A, CREB and NF-κB.

BACKGROUND AND PURPOSE: Prostaglandin E(2) (PGE(2)) stimulation of the G protein-coupled prostanoid EP(1) receptor was found to up-regulate the expression of Nur-related factor 1 (Nurr1) (NR4A2), a transcription factor in the NR4A subfamily of nuclear receptors. The present studies characterize the molecular mechanism of this up-regulation. EXPERIMENTAL APPROACH: The expression of Nurr1 was examined by immunoblot analysis, the polymerase chain reaction and reporter gene assays in human embryonic kidney (HEK) cells stably expressing the recombinant EP(1) receptor and in SH-SY5Y neuroblastoma cells expressing endogenous EP(1) receptors. Signalling pathway inhibitors were used to examine the roles of Rho, PKA, the cAMP response element binding protein (CREB) and NF-κB on the PGE(2) stimulated up-regulation of Nurr1. CREB and NF-κB signalling were also examined by immunoblot analysis and reporter gene assays. KEY RESULTS: The EP(1) receptor mediated up-regulation of Nurr1 was blocked with inhibitors of Rho, PKA, NF-κB and CREB; but PGE(2) failed to significantly stimulate intracellular cAMP formation. PGE(2) stimulation of the EP1 receptor induced the phosphorylation and activation of CREB and NF-κB, which could be blocked by inhibition of PKA. CONCLUSIONS AND IMPLICATIONS: PGE(2) stimulation of the human EP(1) receptor up-regulates the expression of Nurr1 by a mechanism involving the sequential activation of the Rho, PKA, CREB and NF-κB signalling pathways. EP(1) receptors are implicated in tumorigenesis and the up-regulation of Nurr1 may underlie the anti-apoptotic effects of PGE(2) .

Factors leading to obstructive granulation tissue formation after ultraflex stenting in benign tracheal narrowing.

BACKGROUND: This retrospective study aimed to determine the factors leading to obstructive granulation tissue formation after the placement of a self-expandable metallic stent (SEMS) in patients with benign tracheal disease. METHODS: From 2001 to 2007, a total of 67 patients (age: 62.1 +/- 15.4 years; range: 23-87 years) with benign tracheal disease received 75 ultraflex SEMS in our institution. RESULTS: There were 35 SEMSs complicated by obstructive granulation tissue formation out of the 75 stents placed in patients with tracheal disease, giving an incidence of 47.8 % (32/67 patients). The median time until developing granulation tissue was 106 days (IQR, 46-396). Structural airway obstruction prior to SEMS implantation independently predicted obstructive granulation tissue formation after SEMS implantation (odds ratio: 3.84; 95 % CI: 1.01-8.7; P = 0.04). Time to granulation tissue detection was shorter in patients with structural airway obstruction before SEMS implantation (structural airway obstruction vs. dynamic collapse airway: median [IQR] 95 [38-224, n = 26] vs. 396 days [73-994, n = 9]; P = 0.02). CONCLUSIONS: Obstructive granulation tissue formation is not uncommon after SEMS implantation and structural airway obstruction prior to SEMS implantation is an independent predictor. Although SEMS implantation should be restricted to a select population, it may be placed in patients not suitable for surgical intervention or rigid bronchoscopy with anesthesia because of poor pulmonary function.

Cellular origin of fundus autofluorescence in patients and mice with a defective NR2E3 gene.

AIM: To characterise new clinical features in a family with enhanced S-cone syndrome (ESCS) and investigate the pathogenesis of these clinical features in the homozygous Nr2e3(rd7) (rd7) mutant mice. METHODS: Four patients from an affected family were included for genotypic and phenotypic study. Eye tissues from rd7 mice were used to detect a possible relationship between macrophages and autofluorescent material by immunohistochemistry (IHC) staining. RESULTS: Homozygous mutation in R311Q in NR2E3 was detected in this family. Colour photographs revealed that white dots do not correlate to hyperautofluorescent spots seen in autofluorescence imaging of the macula. OCT showed rosette-like lesions similar to those found in rd7 mice histology sections. From IHC analysis, we observed that F4/80 (a pan macrophage marker) and autofluorescence were colocalised to the same cells within the retina rosettes. CONCLUSIONS: The retinal structure of a young ESCS patient with homozygous R311Q mutation in the NR2E3 gene is similar to that seen in the rd7 mice. The macrophages were found to contain autofluorescent materials in the retinal rosettes of rd7 mice. These data are consistent with macrophage infiltration contributing to the hyperautofluorescent spots found in our patients.

Metallic stent and flexible bronchoscopy without fluoroscopy for acute respiratory failure.

Stent implantation has been reported to facilitate liberation from mechanical ventilation in patients with respiratory failure due to central airway disease. The present retrospective cohort study sought to evaluate the risk and benefit of stent implantation via bronchoscopy without fluoroscopic guidance in mechanically ventilated patients. From July 2001 to September 2006, 26 patients with acute respiratory failure were recruited. A bronchoscope was inserted through a mouth guard into the space between the tracheal wall and the endotracheal tube. A guide wire was inserted via the flexible bronchoscope to the lesion site. The bronchoscope was reintroduced through the endotracheal tube. Under bronchoscopic visualisation, the delivery catheter was advanced over the guide wire to deploy the stent. These procedures were successfully performed in 26 patients, with 22 stents placed in the trachea and seven in the main bronchus. Of the 26 patients, 14 (53.8%) became ventilator independent during their stay in the intensive care unit. Severe pneumonia was the most common cause, in seven (58.3%) out of 12 patients, for continued ventilator dependence after stenting. Granulation tissue formation was found in seven patients during the follow-up period. It is concluded that metallic stents can be safely implanted without fluoroscopic guidance in patients with respiratory failure, to facilitate ventilator independence.

Apoptosis-dependent and -independent mechanisms mediate the phagocytic recognition/clearance of the HL60-A1 transfectants with prolonged survival.

OBJECTIVE: The phagocytic recognition and clearance of the recruited inflammatory cells with prolonged survival play a pivotal role in relieving tissue inflammation and maintaining tissue homeostasis. Transgenic mice expressing Bcl-2 in mature neutrophils demonstrated that Bcl-2 attenuated neutrophil apoptosis, while the homeostasis of the neutrophil population was essentially unaffected. This result suggests that clearance of neutrophils with prolonged survival operates independently from apoptosis. Owing to the constitutive and inducible expression of Bcl-2 homologue, A1 in human neutrophils and the intolerance of preparation for the isolated human neutrophils with prolonged survival, the human promyelocytic HL60-A1 transfectants were established to study the mechanism of phagocytic recognition/clearance of the cells with prolonged survival. MATERIALS AND METHODS: The non-apoptotic cells with prolonged survival were enriched by serum withdrawal for five days and negatively isolated by annexin V-binding beads. Then, the cells were labeled with a fluorogenic marker. Monocyte-derived macrophages (MDM) were co-cultured to perform the phagocytosis assay, and flow cytometry was employed to determine the phagocytic index. RESULTS: In the serum-free condition, the phagocytic index of HL60-A1 transfectants was little different from that of the HL60-EGFP control, despite showing a significantly lower degree of apoptosis. While the phagocytic index of HL60-EGFP control was significantly correlated with the degree of apoptosis, the index of the HL60-A1 transfectants was less relevant to it. The phagocytic index for the annexin V-positive cells did not distinguish the two cell types. However, the phagocytic index for the annexin V-negative cells from the HL60-A1 transfectants was increased with age in days. Preincubation of MDM with the scavenger receptor inhibitor, Oxi-LDL, and the inhibitory antibodies against alphavbeta3, CD14 and CD36 surface molecules could attenuate the phagocytic recognition of the annexin V-positive HL60 cells but not the annexin V-negative A1 transfectants with prolonged survival. CONCLUSIONS: This study thus suggests that a mechanism unrelated to apoptosis exists, which mediates the phagocytic clearance of the non-apoptotic cells with prolonged survival and may be associated with A1 function in the myeloid cells.

A regression model using sediment chemistry for the evaluation of marine environmental impacts associated with salmon aquaculture cage wastes.

This study was undertaken to develop an approach for modelling changes of sediment chemistry related to the accumulation of aquaculture waste. Metal composition of sediment Al, Cu, Fe, Li, Mn, and Zn; organic carbon and < 63 microm particles were used to determine the extent of detectable effects around the cage. This study showed marked differences in the sediment chemistry between aquaculture sites and the natural background: (1) negative correlations between sediment Cu and Zn with Al, (2) poor correlations between metals and Li, and (3) concentrations of Fe and Mn decreased with increased accumulation of organic carbon. There is a trend among normalised metals, organic carbon and particles related to normal, hypoxic and anoxic sediment conditions. The trends are useful for detecting and assessing the cumulative effects from aquaculture wastes to the marine environment. Lithium is less interactive with other metals in aquaculture sediments compared with the natural background sediments. Principal components analysis (PCA) was carried out on the metals, organic carbon, and particles to cluster the similarities of the variables so as to establish the predicted or adjusted environmental monitoring program (EMP) ratings. This approach, using the adjusted EMP rating based on sediment chemistry, yields a regression model with R2 = 0.945 compared to R2= 0.653 for the regression model using unadjusted EMP for assessing the environmental conditions.

Distribution of contaminants in biota and sediments in the Musquash Estuary, Atlantic Canada, marine protected area site initiative and contaminant exclusion zone.

The Musquash Estuary, one of the last ecologically intact estuaries in New Brunswick, has been designated an area of interest for a marine protected area (MPA) under the Oceans Act. The area has been assessed for contaminant background levels as required for establishing MPA environmental quality. American lobster (Homarus americanus), blue mussel (Mytilus edulis) and sediments were collected for assessing contaminant levels and distribution in the harbour. Levels of contaminants from the indicator species and the abiotic component have shown: (1) two extremes of high and low Cu and Ag in lobster from the area; and (2) lower metal levels in inner Musquash Harbour sediments and mussels than in those from the harbour mouth. These suggest that deposition of contaminants into the Musquash MPA site was due to transport of contaminants by coastal currents from upstream coastal industrial activities. This reverse trend with higher contaminant levels in the biotic and abiotic components in the outer harbour than in the inner harbour differs from a contaminated harbour and suggests that a contaminant exclusion zone should be considered for controlling contamination from nearby coastal and estuarine industrial sites to protect the sensitive habitats within the marine protected area.

Selection of bioindicators for monitoring marine environmental quality in the Bay of Fundy, Atlantic Canada.

Distribution of metals, PAH's and PCB's in lobsters, mussels, and sediments were used to assess marine environmental quality of the Bay of Fundy. This study demonstrates that the lobster (Homarus americanus) is a better bioindicator for monitoring contaminants in the marine environment and has a greater capacity for the uptake and accumulation of contaminants than the mussel (Mytilus edulis) and sediments. A definite pattern in the spatial distribution of lobster Cu, Cd, and Ag was evident. The distribution of organic contaminants for both mussels and lobsters in the Bay of Fundy lacked a spatial trend, and organic contaminants were undetectable in sediments from all sites. The Gulf Watch Programme, which monitors chemicals in mussels in the Bay of Fundy, did not indicate a problem with high levels of Cu, Cd, and Zn in the ecosystem. Analytes below the detection limit, such as in mussels and sediments, increase the difficulties of chemical analysis and detection for environmental monitoring. Deficiencies of mussels in monitoring the Bay of Fundy were discussed.

Metal contaminants for modelling lobster (Homarus americanus) migration patterns in the Inner Bay of Fundy, Atlantic Canada.

A method, which uses metal compositions in lobster digestive glands as natural environmental tags, has been developed to trace lobster movements. Lobsters were collected from three selected sites, Minas Channel, Minas Basin, and Cobequid Bay, Inner Bay of Fundy, New Brunswick, Canada, that were known to be contaminated with Cu. Five metal variables (Ag, Cd, Cu, Mn and Zn) were processed for principal component analysis (PCA). Metal concentration and burden models were investigated and PCA was able to differentiate lobsters from the respective catch sites. The method was applied to investigate the May and June lobsters collected at the three sites to determine the migration rate during this period of the fishing season. The results show a high level of mixing at Minas Basin and Cobequid Bay in June, and lobster movement inward toward the inner reaches of the bay, with very limited movement outward from the inner bay.

Aquaculture-related trace metals in sediments and lobsters and relevance to environmental monitoring program ratings for near-field effects.

The study was undertaken to assess the marine environmental effects from feed and waste associated with aquaculture activities. Metal compositions of sediment, lobster, and feed were used to evaluate the extent of detectable effects at 0 m (under the cage) and 50 m distance. Sediments that were collected under the cages and were characterised as hypoxic or anoxic, showed elevated levels of Cu, Zn, organic carbon, and % <63 microm particles, and low Mn and Fe. At 50 m there was a major reduction in waste chemical impact. Using lobster, a bioindicator species, as a tool for detecting near-field impacts, showed accumulations of high Cu associated with active aquaculture sites. Chemical compositions and metal ratios normalised with organic carbon, were used to assess the sediment conditions associated with environmental monitoring program ratings (EMP--normal, hypoxic, and anoxic). Principal component analysis (PCA) was used to explore chemical data at all sites for differentiating normal, hypoxic and anoxic sediment conditions. Selected variables (Cu, Zn, Fe, Mn, organic carbon, and particles <63 microm) were sufficient for the PCA approach with >90% explainable variance of first two components. The groupings based on PCA and cluster analysis were similar to EMP classifications with some exceptions of mis-identification by EMP. The sediment chemistry components were valid indicators for evaluating marine environmental conditions and for assessing aquaculture operating sites. The developed techniques, using chemical variables in combination with EMP and the statistical approach should be useful to predict the effects of aquaculture practices and the suitability of aquaculture operations.

97- and 117-kDa forms of collecting duct urea transporter UT-A1 are due to different states of glycosylation.

UT-A1 is an extremely hydrophobic 929-amino acid integral membrane protein, expressed in the renal inner medullary collecting duct, with a central role in the urinary concentrating mechanism. Previous immunoblotting studies in rats have revealed that UT-A1 is present in kidney in 97- and 117-kDa monomeric forms and that the relative abundance of the two forms is altered by vasopressin treatment and other treatments that altered urinary inner medullary urea concentration. The present studies were carried out using protein chemistry techniques to determine the origin of the two forms. Peptide-directed polyclonal antibodies targeted to five sites along the polypeptide sequence from the NH2 to the COOH terminus labeled both forms, thus failing to demonstrate a significant deletion in the primary amino acid chain. The 97- and 117-kDa monomeric forms were both reduced to 88 kDa by deglycosylation with N-glycosidase F, indicating that a single polypeptide chain is glycosylated to two different extents. Studies using nonionic detergents for membrane solubilization or using homobifunctional cross-linkers demonstrated that UT-A1 exists as a 206-kDa protein complex in native kidney membranes. The mobility of this complex was also increased by deglycosylation. Both the 97- and 117-kDa proteins, as well as the 206-kDa complex, were immunoprecipitated with UT-A1 antibodies. We conclude that UT-A1 is a glycoprotein and that the two monomeric forms (97 and 117 kDa) in inner medullary collecting duct are the consequence of different states of glycosylation.

HLA-DM recognizes the flexible conformation of major histocompatibility complex class II.

DM facilitates formation of high affinity complexes of peptide-major histocompatibility complex (MHC) by release of class II MHC-associated invariant chain peptide (CLIP). This has been proposed to occur through discrimination of complex stability. By probing kinetic and conformational intermediates of the wild-type and mutant human histocompatibility leukocyte antigen (HLA)-DR1-peptide complexes, and examining their reactivities with DM, we propose that DM interacts with the flexible hydrophobic pocket 1 of DR1 and converts the molecule into a conformation that is highly peptide receptive. A more rigid conformation, generated upon filling of pocket 1, is less susceptible to DM effects. Thus, DM edits peptide-MHC by recognition of the flexibility rather than stability of the complex.