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Doxycycline hyclate (DCH) and minocycline hydrochloride (MH) are tetracycline antibiotics and broad-spectrum antimicrobial agents. The changes in DCH and MH under blue light (λ = 462 nm) irradiation in alkaline conditions (BLIA) were investigated. Deactivation caused by superoxide anion radical (O2•−) and deactivation from DCH and MH during photolysis on Staphylococcus aureus (S. aureus), including methicillin-resistant S. aureus (MRSA), were studied. DCH is relatively unstable compared to MH under BLIA. The level of O2•− generated from the MH-treated photoreaction is lower than that from DCH photolysis, and the DCH-treated photoreaction is more efficient at inactivating S. aureus and MRSA at the same radiant intensity. DCH subjected to BLIA decreased the viability of S. aureus and MRSA by 3.84 and 5.15 log, respectively. Two photolytic products of DCH (PPDs) were generated under BLIA. The mass spectra of the PPDs featured molecular ions at m/z 460.8 and 458.8. The molecular formulas of the PPDs were C21H22N2O10 and C22H24N2O9, and their exact masses were 462.44 and 460.44 g/mol, respectively. These results bolster the photolytic oxidation that leads to DCH-enhanced deactivation of S. aureus and MRSA. Photochemical treatment of DCH could be applied as a supplement in hygienic processes.

Background Currently available topical treatments for actinic keratosis (AK) are associated with substantial side-effects. Objectives To evaluate the efficacy and safety of topical SR-T100 gel in treating AK. Methods A multicenter, randomized, double-blinded phase III trial was conducted. Patients with at least two clinically visible AK were enrolled and a punch biopsy was performed on one of the AK to confirm the diagnosis. This study consisted of up to 16-week treatment and 8-week post-treatment periods. Medication was applied daily with occlusive dressing. Results 123 subjects were recruited and 113 were randomized. 76 subjects were in the SR-T100 and 37 in the vehicle arms. In SR-T100 and vehicle groups, 32.39% and 17.14% of subjects achieved complete clearance, respectively. For 75% partial clearance of lesions, 71.83% and 37.1% of subjects achieved this goal in SR-T100 and vehicle group, respectively. When comparing SR-T100 to vehicle, the odds ratio of complete clearance was 2.14 (p = 0.111), and odds ratio of partial clearance was 4.36 (p Conclusion The imitation of the study was that not all the treated AK lesions were confirmed by histopathology. The diagnostic uncertainty may contribute to the high partial clearance rate in the vehicle group since the clinical-diagnosed AK showed higher clearance rate compared to histopathology-confirmed AK. The use of occlusive dressing was another possible explanation for high placebo effects. The results suggested that topical SR-T100 gel may be an effective and safe treatment for field therapy of AK.

BACKGROUND Burn blister fluid contains several angiogenic factors to promote wound neovascularization. In our previous study, we found that deep partial-thickness burn (DPTB) wounds showed higher expression levels of angiogenin to enhance vascularization compared with superficial partial-thickness burn wounds. Neovascularization is a complex process that involves an interaction between circulating angiogenic cells and mediators. We hypothesized that in addition to angiogenic factors burn blisters may contain specific cell types. The aim of the present study was to characterize the specific cells present in burn blisters. METHODS Twenty-four burn blister fluid samples were obtained with informed consent from patients with superficial partial-thickness burn (n = 16) or DPTB (n = 8) wounds. Blister cells were isolated from individual intact blisters and characterized with flow cytometry analysis using CD14, CD34, vascular endothelial growth factor receptor 2, and CD133 markers. CD14 and CD34 blister cells were also isolated using a magnetic-activated cell sorting system to examine their potential for endothelial differentiation. Angiogenin levels in the burn blister fluids were evaluated with enzyme-linked immunosorbent assay. RESULTS CD14 cells were the most highly represented cell type in the burn fluids of both groups, although a significantly greater percentage of CD14 cells were observed in DPTB fluids. CD14 blister cells had a higher potency to differentiate into functional endothelial cells as compared with CD34 cells. The proportion of CD14 cells gradually increased after burn injury. In contrast to CD14 cells, angiogenin showed the highest expression levels at day 1 postburn. With regard to burn wound neovascularization, angiogenin expression was partially correlated with CD14 blister cells in the burn fluids. CONCLUSIONS We provide the first report on the characterization of blister cells in burn fluids. Our data suggest that CD14 blister cells may play a role in burn wound neovascularization. Measurement of CD14 blister cells serves as a possible tool for assessing burn wound status.

Background Effective management of psoriasis is a cause for much concern. In Taiwan, there is a lack of consensus on management strategies for psoriasis, especially the principles of drug prescribing in psoriatic patients. Objectives The Taiwanese Dermatological Association convened Expert Panel meetings three times between 2012 and 2015 to discuss the management strategies for treatment of psoriasis in order to fill the knowledge gap and provide a reference tool for Taiwanese dermatologists. Results This paper reports the final output from the three meetings, with the aim of aiding clinical decision making in terms of principles of prescribing, including dosing strategies, efficacy profiles, and safety concerns in connection with eight categories of antipsoriatic treatment: topical agents, phototherapy, nonbiologic conventional systemic agents, licensed biologic systemic agents, newly emerging therapies, combination therapy, transitional therapy, and traditional Chinese medicine. Conclusion The Expert Panel, comprising distinguished Taiwanese dermatologists, succeeded in developing a consensus about the management of psoriasis in Taiwanese patients. Unavailability of data in certain areas may suggest a possibility of new directions in research.

Traditional wound care methods include wound infection control, adequate nutritional supplements, education of changing position every 2–3 h to avoid tissue hypoxia, vacuum assistant closure, debridement, skin graft, and tissue flap. Electric current stimulation, ultrasound, laser, and hydrotherapy have emerged as adjuvant therapies. However, most, if not all, of these therapies are expensive, and the treatment results are variable. The development of the active methods to improve wound healing is mandatory. CO2 administration has been known to improve microcirculation and local oxygen supply that are beneficial to wound healing. Here, the metal ion-ligand coordination nanoarchitecture was designed to reveal NIR light-induced CO2 generation for wound healing. The administration simply topically dropped the colloidal solution on the incisional wound, followed by exposure of near-infrared (NIR) lamp to yield CO2, resulting in the observation of the accelerated wound healing.

Human cardiac progenitor cells isolated from the same host may have advantages over other sources of stem cells. The aim of this study is to establish a new source of human progenitor cells collected from a waste product, pericardiac effusion fluid, after open-heart surgery in children with congenital heart diseases. The fluid was collected every 24 h for 2 days after surgery in 37 children. Mononuclear cells were isolated and expanded in vitro. These pericardial effusion-derived progenitor cells (PEPCs) exhibiting cardiogenic lineage markers, were highly proliferative and enhanced angiogenesis in vitro. Three weeks after stem cell transplantation into the ischemic heart in mice, cardiac ejection fraction was improved significantly without detectable progenitor cells. Gene expression profiles of the repaired hearts revealed activation of several known repair mechanisms including paracrine effects, cell migration, and angiogenesis. These progenitor cells may have the potential for heart regeneration.

Methicillin-resistant Staphylococcus aureus (MRSA) skin-wound infections are associated with considerable morbidity and mortality. Indocyanine green (ICG), a safe and inexpensive dye used in clinical imaging, can be activated by near-infrared in photodynamic therapy (PDT) and photothermal therapy (PTT) to effectively kill MRSA. However, how this treatment affects MRSA drug sensitivity remains unknown. The drug-sensitivity phenotypes, bacterial growth rate, and cell-wall thickness of three MRSA strains were analyzed after ICG-PDT. Drug-resistant gene expressions were determined by polymerase chain reaction (PCR) and quantitative reverse transcription (qRT)-PCR. Related protein expressions were examined with immunoblotting. Drug sensitivity was further evaluated in animal models. MRSA that survived the treatment grew faster, and the cell wall became thinner compared to parental cells. These cells became more sensitive to oxacillin, which was partly related to mecA complex gene deletion. Skin necrosis caused by ICG-PDT-treated MRSA infection was smaller and healed faster than that infected with parental cells. With oxacillin therapy, no bacteria could be isolated from mouse lung tissue infected with ICG-PDT-treated MRSA. ICG-PDT drives MRSA toward an oxacillin-sensitive phenotype. It has the potential to develop into an alternative or adjuvant clinical treatment against MRSA wound infections.

Methicillin-resistant Staphylococcus aureus (MRSA) skin-wound infections are associated with considerable morbidity and mortality. Indocyanine green (ICG), a safe and inexpensive dye used in clinical imaging, can be activated by near-infrared in photodynamic therapy (PDT) and photothermal therapy (PTT) to effectively kill MRSA. However, how this treatment affects MRSA drug sensitivity remains unknown. The drug-sensitivity phenotypes, bacterial growth rate, and cell-wall thickness of three MRSA strains were analyzed after ICG-PDT. Drug-resistant gene expressions were determined by polymerase chain reaction (PCR) and quantitative reverse transcription (qRT)-PCR. Related protein expressions were examined with immunoblotting. Drug sensitivity was further evaluated in animal models. MRSA that survived the treatment grew faster, and the cell wall became thinner compared to parental cells. These cells became more sensitive to oxacillin, which was partly related to mecA complex gene deletion. Skin necrosis caused by ICG-PDT-treated MRSA infection was smaller and healed faster than that infected with parental cells. With oxacillin therapy, no bacteria could be isolated from mouse lung tissue infected with ICG-PDT-treated MRSA. ICG-PDT drives MRSA toward an oxacillin-sensitive phenotype. It has the potential to develop into an alternative or adjuvant clinical treatment against MRSA wound infections.

Objective: Cell migration is an essential process in skin wound healing. Photodynamic therapy (PDT) enhances wound healing by photoactivating a photosensitizer with a specific wavelength of light. Cystic fibrosis transmembrane conductance regulator (CFTR) is an ion channel expressed in multiple layers of keratinocytes. Recent studies showed that the activation of CFTR-related downstream signaling affects skin wound healing. We examined whether indocyanine green (ICG)-mediated PDT-enhanced cell migration is related to CFTR activation. Approach: The spatial and temporal expression levels of CFTR and proteins involved in focal adhesion, including focal adhesion kinase (FAK) and paxillin, were evaluated during cell migration in vitro and in vivo for wound healing. Results: ICG-PDT-conditioned medium collected from cells exposed to 5 J/cm(2) near-infrared light in the presence of 100 μg/mL ICG activated CFTR and enhanced HaCaT cell migration. The expression of phosphorylated FAK Tyr861 and phosphorylated paxillin in focal adhesions was spatially and temporally regulated in parallel by ICG-PDT-conditioned medium. Curcumin, a nonspecific activator of CFTR, further increased PDT-enhanced cell migration, whereas inhibition of CFTR and FAK delayed cell migration. The involvement of CFTR in ICG-PDT-enhanced skin wound healing was confirmed in a mouse back skin wound model. Innovation: CFTR is a potential new therapeutic target in ICG-PDT to enhance wound healing. Conclusion: ICG-PDT-enhanced cell migration may be related to activation of the CFTR and FAK pathway. Conditioned medium collected from ICG-PDT may be useful for treating patients with chronic skin ulcer by regulating CFTR expression in keratinocytes.

Photodynamic therapy (PDT) works through photoactivation of a specific photosensitizer (PS) in a tumor in the presence of oxygen. PDT is widely applied in oncology to treat various cancers as it has a minimally invasive procedure and high selectivity, does not interfere with other treatments, and can be repeated as needed. A large amount of reactive oxygen species (ROS) and singlet oxygen is generated in a cancer cell during PDT, which destroys the tumor effectively. However, the efficacy of PDT in treating a deep-seated tumor is limited due to three main reasons: Limited light penetration depth, low oxygen concentration in the hypoxic core, and poor PS accumulation inside a tumor. Thus, PDT treatments are only approved for superficial and thin tumors. With the advancement of nanotechnology, PDT to treat deep-seated or thick tumors is becoming a reachable goal. In this review, we provide an update on the strategies for improving PDT with nanomedicine using different sophisticated-design nanoparticles, including two-photon excitation, X-ray activation, targeting tumor cells with surface modification, alteration of tumor cell metabolism pathways, release of therapeutic gases, improvement of tumor hypoxia, and stimulation of host immunity. We focus on the difficult-to-treat pancreatic cancer as a model to demonstrate the influence of advanced nanomedicine in PDT. A bright future of PDT application in the treatment of deep-seated tumors is expected.

The adaptability of bacterial resistance to antibiotics contributes to its high efficiency during evolution. Tetracycline (TC) is a broad-spectrum antimicrobial agent. Chromatographic analyses and mass spectrometry were used to study the effects of the light illumination of a 462 nm light-emitting diode (LED) on the conformational changes of TC in a phosphate buffer solution (PBS, pH 7.8). Especially, the inactivation of superoxide anion radicals (O2•−) and Escherichia coli (E. coli), including that of a multidrug-resistant E. coli (MDR E. coli), were investigated during the photolysis of TC. A photolysis product of TC (PPT) was generated in an alkaline solution after the illumination of a blue light. The mass spectra of PPT had characteristic ion signals in m/z 459, 445, and 249.1 Da. The PPT has the molecular formula of C22H22N2O9, and the exact mass is 458.44 g/mol. The inactivation of MDR E. coli is not significant with TC treatment. The drug-resistant ability of MDR E. coli has a less significant effect on PPT, and the changed conformation of TC retained the inactivation ability of MDR E. coli upon blue light photoreaction. With TC, illuminated by a blue light in a pH 7.8 PBS, O2•− was generated from TC photolysis, which enhanced the inactivation of E. coli and MDR E. coli. A 96.6% inactivation rate of MDR E. coli was reached with TC under 2.0 mW/cm2 blue light illumination at 25 ± 3 °C for 120 min, and the effects of the TC-treated photoreaction on MDR E. coli viability repressed the growth of MDR E. coli by 4 to 5 logs. The present study of the blue light photoreaction of TC offers a new approach to the inactivation of MDR E. coli.

Background/Objectives Recently, fibrotic diseases such as hypertrophic scar, keloid, and scleroderma have been treated with UV-A1 radiation with encouraging results. However, conventional UV light sources are bulky and expensive. In this study, we aimed to verify the effectiveness of a portable UV-A1 radiation device in treating hypertrophic scars. Materials and methods A light-emitting diode array that emitted 365 ± 5 nm (UV-A1) was used to irradiate fibroblasts and hypertrophic scar in a rabbit model. Results In cell cultures, UV-A1 light exposure inhibited post-wound cell migration and reduced the total amount of soluble collagen production in fibroblasts. Type I collagenase production and its activity increased after treatment. On the rabbit ear, UV-A1 light irradiation reduced the thickness of hypertrophic scars, confirming the antifibrotic effect in vivo. Conclusion These results support the potential of a portable UV-A1 light device in treating hypertrophic scar.

Summary The physiology of human skin pigmentation is varied and complex, with an extensive melanogenic paracrine network involving mesenchymal and epithelial cells, contributing to the regulation of melanocyte survival and proliferation and melanogenesis. Mutations in several genes, involving predominantly the KIT ligand/c-Kit and Ras/mitogen-activated protein kinase signalling pathways, have been implicated in a spectrum of diseases in which there is hyperpigmentation, hypopigmentation or both. Here, we report on a 12-year-old girl from Taiwan with a 6-year history of diffuse progressive skin hyperpigmentation resulting from a different aetiology: an inborn metabolic disorder of vitamin B12 (cobalamin), designated cblJ. Using whole-exome sequencing we identified a homozygous mutation in ABCD4 (c.423C>G; p.Asn141Lys), which encodes an ATP-binding cassette transporter with a role in the intracellular processing of cobalamin. The patient had biochemical and haematological evidence of cobalamin deficiency but no other clinical abnormalities apart from a slight lightening of her previously black hair. Of note, she had no neurological symptoms or signs. Treatment with oral cobalamin (3 mg daily) led to metabolic correction and some reduction in the skin hyperpigmentation at the 3-month follow-up. This case demonstrates that defects or deficiencies of cobalamin should be remembered in the differential diagnosis of diffuse hyperpigmentary skin disorders.

Wound healing is a natural process to restore the structure and function of injured or diseased tissues. Repair of a skin wound usually leads to a scar while regeneration implies fully recovery of function and structure of the damaged tissue. Adult skin wound usually heals with scar while fetal skin heals scarless. Hair regeneration in elderly scalp wound has never been observed. We reported an 80-year-old patient with a large wound on the scalp after excision of a basal cell carcinoma healed by secondary intention wound healing. The patient's wound healed very well aesthetically. Interestingly, on approximate post wound day 180, a hair was observed to be growing towards the surface and eventually erupted in the center of the wound. The hair remained black at 42-month follow-up. This case demonstrated that neogenesis of hair is possible even in geriatric patient. To the best of our knowledge, this is the first report of hair regrow in human skin after wound healing.

Traditional wound care methods include wound infection control, adequate nutritional supplements, education of changing position every 2-3 h to avoid tissue hypoxia, vacuum assistant closure, debridement, skin graft, and tissue flap. Electric current stimulation, ultrasound, laser, and hydrotherapy have emerged as adjuvant therapies. However, most, if not all, of these therapies are expensive, and the treatment results are variable. The development of the active methods to improve wound healing is mandatory. CO

The light sensitive compound riboflavin-5′-phosphate (or flavin mononucleotide, FMN) generates reactive oxygen species (ROS) upon photo-irradiation. FMN is required by all flavoproteins because it is a cofactor of biological blue-light receptors. The photochemical effects of FMN after irradiation by blue or violet light on the inactivation of Staphylococcus aureus strains, including a methicillin-resistant strain (MRSA), were investigated in this study. Upon blue- or violet-light photo-treatment, FMN was shown to inactivate S. aureus due to the generated ROS. Effective bacterial inactivation can be achieved by FMN photolysis without an exogenous electron provider. Inactivation rates of 94.9 and 95.2% in S. aureus and MRSA, respectively, can be reached by blue light irradiation (2.0 mW/cm 2 ) with 120 μM FMN for 120 min. A lower FMN concentration and a shorter time are required to reach similar effects by violet light irradiation. Inactivation rates of 96.3 and 97.0% in S. aureus and MRSA, respectively, can be reached by violet light irradiation (1.0 mW/cm 2 ) with 30 μM FMN for 30 min. The sensitivity of the inherent photosensitizers is lower under blue-light irradiation. A long exposure photolytic treatment of FMN by blue light is required to inactivate S. aureus . Violet light was found to be more efficient in S. aureus inactivation at the same radiant intensity. FMN photolysis with blue or violet light irradiation enhanced the inactivation rates of S. aureus and MRSA. FMN photochemical treatment could be a supplemental technique in hygienic decontamination processes.

There are limited studies regarding childhood and adolescent psoriasis in Taiwan. A total of 86 pathologically confirmed cases diagnosed from 1989 to 2017 were retrospectively reviewed. Mean disease onset age was 10.51 years, and plaque psoriasis was the most common type. Compared to studies on Caucasian and other Asian populations, we found a lower estimated prevalence, higher rate of psoriasis limited to the nail at presentation, and higher prevalence of psoriatic arthritis. The most common comorbidities were related to atopy and metabolic syndrome. Positive family history of psoriasis and psoriasis preceded by infection were significantly associated with moderate-to-severe disease.

Dermatofibrosarcoma protuberans (DFSP) is a rare soft-tissue neoplasm in children with low-grade malignant potential; metastasis is rare but there is risk of local recurrence after treatment.1 An adequate surgical tumor-free margin is vital for long-term outcome and survival after wide excision or Mohs micrographic surgery.1 However, such surgeries may result in severe functional and cosmetic defects at anatomically critical areas. Neoadjuvant or adjuvant imatinib mesylate therapy may help control tumor progression, but treatment experience in pediatric DFSP is limited to case reports and there is no established treatment protocol. We report a toddler boy with a DFSP near his left eye treated with adjuvant imatinib mesylate after an inadequate postoperative tumor-free margin.

Department of Mathematics and Information Technology, Hong Kong Institute of Education, Hong Kong SAR, China; Email: yiuchi@ied.edu.hk (Received February 5, 2013; Revised March 6, 2013; Accepted March 21, 2013) This paper aims to explore whether Learning Study improves teachers’ subject content knowledge, pedagogical content knowledge, and attitude toward teaching mathematics. A Learning Study was conducted in a Hong Kong primary school for a research lesson on comparing the size of fractions to explore the new teacher roles.

Micro-plasma is a possible alternative treatment for wound management. The effect of micro-plasma on wound healing depends on its composition and temperature. The authors previously developed a capillary-tube-based micro-plasma system that can generate micro-plasma with a high nitric oxide-containing species composition and mild working temperature. Here, the efficacy of micro-plasma treatment on wound healing in a laser-induced skin wound mouse model was investigated. A partial thickness wound was created in the back skin of each mouse and then treated with micro-plasma. Non-invasive methods, namely wound closure kinetics, optical coherence tomography (OCT), and laser Doppler scanning, were used to measure the healing efficiency in the wound area. Neo-tissue growth and the expressions of matrix metallopeptidase-3 (MMP-3) and laminin in the wound area were assessed using histological and immunohistochemistry (IHC) analysis. The results show that micro-plasma treatment promoted wound healing. Micro-plasma treatment significantly reduced the wound bed region. The OCT images and histological analysis indicates more pronounced tissue regrowth in the wound bed region after micro-plasma treatment. The laser Doppler images shows that micro-plasma treatment promoted blood flow in the wound bed region. The IHC results show that the level of laminin increased in the wound bed region after micro-plasma treatment, whereas the level of MMP-3 decreased. Based on these results, micro-plasma has potential to be used to promote the healing of skin wounds clinically.

Field experience at the Hong Kong Institute of Education (HKIEd) is viewed as a central aspect to our programmes. The proposed chapter will discuss a project that aimed to enhance student teachers' professional development in FE by adopting mobile technology and cloud services. Also, the use of digital forms of FE documents such as TP supervision forms, FE portfolios, and reflective journals enables student teachers and Institute supervisors to build their own e-portfolio for further sharing of their professional practices within and outside the Institute.

Background: Rigorous research efforts have been undertaken worldwide to develop a needle-free insulin delivery for many decades with limited success. This translational study aims to deliver insulin through skin with painless electroporation. Methods: A recently designed microelectrode array was used to deliver insulin in mice with diabetes under electroporation conditions that are painless and harmless on human skin. Results: Under such condition, a therapeutic amount of insulin was delivered successfully through mouse skin. Electroporation alone increased insulin transport around 100-fold compared with passive diffusion. Increased skin temperature to 40°C for 20 min augmented insulin transport to 237-fold more than the control value. Repeated electroporation showed no harm on human skin. Conclusion: The results indicate the potential of painless delivery of insulin through human skin in future clinical practice.

Molecular mimicry between group A streptococcus and host antigens has important roles in the development of post-streptococcal sequelae, including glomerulonephritis and rheumatic heart disease (RHD). The etiology of RHD involves host cross-reactivity with M proteins and carbohydrate antigens. In this study, we show that anti-streptococcal pyrogenic exotoxin B (SPE B) antibodies exhibited characteristics of autoantibodies, which cross-react with endothelial cells. Immunoglobulin G (IgG) deposition and complement activation were observed in the heart valve of SPE B-immunized mice. In addition, apoptosis in the heart valve was detected in SPE B-immunized mice. An anti-SPE B monoclonal antibody (mAb) 10G showed cross-reactivity with human microvascular endothelial (HMEC-1) cells and mouse valve endothelial cells. Passive immunization with mAb 10G also caused IgG deposition, complement activation, and apoptotic cell death in the mouse heart valve. We conducted peptide array and ELISA using synthetic peptides to identify the SPE B antigenic epitope recognized by mAb 10G. Results showed that the major epitope of mAb 10G is localized to amino-acid residues 296-310 of SPE B (P7-8). The cross-reactivity of mAb 10G with endothelial cells was inhibited using P7-8 peptides for competition. These results suggest that anti-SPE B antibodies cross-react with endothelial cells, and that a dominant epitope is located within the amino-acid residues 296-310 of SPE B. Moreover, we found that mAb 10G can also bind to N-acetyl-β-D-glucosamine (GlcNAc) conjugated with bovine serum albumin (BSA), but not to BSA or M1 protein. Competition assay showed that the binding activity of mAb 10G with GlcNAc-BSA and P7-8 of SPE B was inhibited by pretreatment with GlcNAc-BSA or P7-8 peptides. Therefore, our results suggest that conformational molecular mimicry may exist between SPE B and GlcNAc.

The adaptability of bacterial resistance to antibiotics contributes to its high efficiency during evolution. Tetracycline (TC) is a broad-spectrum antimicrobial agent. Chromatographic analyses and mass spectrometry were used to study the effects of the light illumination of a 462 nm light-emitting diode (LED) on the conformational changes of TC in a phosphate buffer solution (PBS, pH 7.8). Especially, the inactivation of superoxide anion radicals (O2&bull, &minus, ) and Escherichia coli (E. coli), including that of a multidrug-resistant E. coli (MDR E. coli), were investigated during the photolysis of TC. A photolysis product of TC (PPT) was generated in an alkaline solution after the illumination of a blue light. The mass spectra of PPT had characteristic ion signals in m/z 459, 445, and 249.1 Da. The PPT has the molecular formula of C22H22N2O9, and the exact mass is 458.44 g/mol. The inactivation of MDR E. coli is not significant with TC treatment. The drug-resistant ability of MDR E. coli has a less significant effect on PPT, and the changed conformation of TC retained the inactivation ability of MDR E. coli upon blue light photoreaction. With TC, illuminated by a blue light in a pH 7.8 PBS, O2&bull, was generated from TC photolysis, which enhanced the inactivation of E. coli and MDR E. coli. A 96.6% inactivation rate of MDR E. coli was reached with TC under 2.0 mW/cm2 blue light illumination at 25 &plusmn, 3 &deg, C for 120 min, and the effects of the TC-treated photoreaction on MDR E. coli viability repressed the growth of MDR E. coli by 4 to 5 logs. The present study of the blue light photoreaction of TC offers a new approach to the inactivation of MDR E. coli.

Objectives We tested whether methylene blue, an inexpensive and safe photosensitizer, is feasible for photodynamic inactivation of enterovirus 71 (EV71) in the environment. Methods By escalating light doses and photosensitizer concentrations, photoinactivation of EV71 and other enteroviruses was examined in vitro. Viral transmission in the environment was simulated with a neonatal mouse model in vivo. Possible mechanisms were analysed with alterations of viral DNA and proteins after treatments. Results Photodynamic inactivation of EV71 in suspensions occurred in a dose-dependent manner. The optimal condition for photoinactivating EV71 required a light dose of 200 J/cm(2) in the presence of methylene blue. This photodynamic condition was also able to inactivate other enteroviruses, including poliovirus 1 and coxsackieviruses A2, A3, A16 and B3. In an imitation environment, EV71 spread on a solid surface was inactivated by methylene blue-mediated photodynamic inactivation and prevented EV71 transmission to mice. Western blot and RT-PCR analysis indicated that both the viral proteins and the genome were disrupted after photodynamic inactivation. Conclusions Methylene blue-mediated photodynamic inactivation may provide a novel way to eliminate environmentally contaminated sources of EV71 to prevent infection.

Catechin is a flavan-3-ol, a derivative of flavans, with four phenolic hydroxyl groups, which exhibits a wide range of physiological properties. Chromatographic analyses were employed to examine the effects of blue light irradiation on the changes of catechin hydrate in an alkaline condition. In particular, the detection of a superoxide anion radical (O2&bull, &minus, ), a reactive oxygen species (ROS), and the inactivation of Acinetobacter baumannii (A. baumannii)&mdash, including a carbapenem-resistant A. baumannii (CRAB)&mdash, was investigated during the photoreaction of catechin hydrate. Following basification with blue light irradiation, the transparent solution of catechin hydrate turned yellowish, and a chromogenic catechin dimer was separated and identified as a proanthocyanidin. Adding ascorbic acid during the photolytic treatment of catechin hydrate decreased the dimer formation, suggesting that ascorbic acid can suppress the photosensitive oxidation of catechin. When catechin hydrate was irradiated by blue light in an alkaline solution, O2&bull, was produced via photosensitized oxidation, enhancing the inactivation of A. baumannii and CRAB. The present findings on the photon-induced oxidation of catechin hydrate provides a safe practice for the inactivation of environmental microorganisms.

When we examine the recent official curriculum documents published by the Curriculum Development Council in Hong Kong, we can observe that generic skills such as Collaboration Skills, Communication Skills, Creativity, Critical Thinking Skills, Problem-solving Skills etc. are identified as fundamental in helping students to learn. As most people agree that creativity is an essential element in the computer world, we are going to discuss the ways to develop students' creative ability in computer lessons in this paper.

The aim of this study was to investigate the expression of interleukin-20 (IL-20) and its receptors on psoriatic skin by immunohistochemical analysis and to evaluate the correlation of CD8-positive T lymphocytes with epidermal proliferation. Overexpression of IL-20 and its receptors was detected in the keratinocytes of the lesional skin of psoriasis and spongiotic dermatitis. The expression pattern of IL-20 spreads throughout the whole layer of epidermis, while IL-19 was expressed in up to three or four layers suprabasally. The serum level of IL-20 in psoriatic patients was significantly lower than that in healthy controls. IL-20 upregulated KGF transcripts on CD8-positive T cells. We hypothesize that overexpression of IL-20 is correlated with keratinocyte proliferation that acts through their receptor complex expressed by keratinocytes themselves. Furthermore, IL-20 can stimulate CD8-positive lymphocytes to produce KGF, which may contribute to sustaining the hyperproliferative status of the keratinocytes.

Background For preservation of integrity of appearance and function in a 66-year-old male with an extremely rare case of verrucous carcinoma developing from the subungium of his right thumb, intra-arterial infusion with methotrexate was used. Objective To evaluate the effectiveness of arterial infusion with methotrexate in this unusual nail bed cancer. Methods Right brachial arterial catheterization and infusion with methotrexate (50 mg) were used every 24 hours together with simultaneous intramuscular injection of 6 mg of leucovorin every 6 hours for 10 days. Results At 4 years, 8 months after therapy, the patient was in sustained complete remission with a functionally normal right thumb. Conclusion This case study suggests that intra-arterial infusion chemotherapy is a simple and effective method for thumb subungual verrucous carcinoma with the unique advantage of preservation of morphology and functional conditions. It can be considered an effective treatment option.

Photodynamic therapy (PDT) is an evolving cancer treatment with promising results in treating malignant tumors by photoactivation of a photosensitizer with a specific wavelength. The second generation photosensitizer mono-L-aspartyl chlorin e6 (NPe6) was reported to have significant efficacy in killing cancer cells in vitro and in vivo. Though topical application might yield a higher local concentration and less systemic side effect, no data concerning topical absorption of NPe6 is available even though the drug has already been used in clinical trial for several years. To evaluate the possibility of topical delivery of NPe6 via an animal model, escalated concentrations of NPe6 were applied to BALB/c mouse skin for a different time periods after barrier disruption with tape stripping. Since NPe6 fluorescence intensity and drug concentration in tissue was well correlated, we evaluated drug penetration depth with frozen sections of treated and non-treated skin under a fluorescence microscope. An on-line fluorescence imaging system was used to monitor the NPe6 fluorescence kinetics in the skin. The fluorescence microscope confirmed successful topical delivery of NPe6 in mouse skin with or even without barrier disruption. Orange to red NPe6 fluorescence appeared at the epidermis, dermis, and even the muscular layer when using 10 mg/ml NPe6 application. The fluorescence intensity peaked at 1 h and revealed a dose-dependent response pattern. NPe6 treated versus non-treated skin showed a statistically significant difference by Student’s t-test (P

SummaryBackground Photodynamic therapy (PDT) using topical application of 5-aminolaevulinic acid (ALA) has been widely reported for the treatment of a variety of neoplastic and non-neoplastic cutaneous diseases. Although different formulations containing variable amounts of ALA have been applied in PDT, the dose–response relationships between transdermal ALA delivery and cutaneous protoporphyrin IX (PpIX) accumulation have not been studied. Objectives and methods The objectives of this study were to investigate the effect of permeability barrier function, ALA concentration and formulation on the in vitro penetration of ALA through nude mouse skin and cutaneous PpIX formation at 2 h following a 2-h application of ALA to nude mouse skin in vivo, and to delineate the relationships in between. Results Results demonstrated that variations in barrier integrity, in addition to ALA concentration, profoundly influenced ALA delivery to generate PpIX. Saturable correlations were found to exist between PpIX concentrations in both the epidermis and dermis in vivo and its transdermal flux in vitro, and the relationships were well described by the Emax model. The established correlations based on pure aqueous solutions were applicable to different formulations containing hydroxypropylmethylcellulose as the gelling agent and ethylenediamine tetraacetic acid as the iron chelator. Moreover, incorporation of desferrioxamine, another iron chelator, in the formulation prolonged cutaneous PpIX accumulation in the skin in comparison with 3% ALA aqueous solution, but the peak PpIX levels were not increased. Application of a liposomal formulation resulted in similar prolongation in ALA-induced PpIX accumulation, as well as better epidermal targeting. Conclusions Knowledge of the dose–response relationships and the effect of formulation is important for designing optimal formulations and treatment schedules for topical ALA-PDT.

Background. Surgical excision is the preferred method of eradicating Bowen's disease (BD). However, when BD occurs on the digit, surgical intervention can sometimes lead to scar contracture and loss of function of the digit. Objective. To evaluate the effectiveness of photodynamic therapy (PDT) in eradicating BD of the digit while preserving the full function of the digit. Methods. Four patients of chronic arsenism with biopsy-proven BD on the digit were treated with PDT by using a newly designed light-emitting diode (LED) array with a peak wavelength of 630 nm (630 ± 40 nm; 40 mW/cm2 at skin surface). After partial removal of the thickened horny layer and 16 hours of occlusion with a 2% aminolevulinic acid (ALA) solution, each lesion was irradiated with 240 J/cm2 in two fractions with a 90-minute interval. Results. All patients experienced a significant burning, tingling sensation that was tolerable during the procedure except one who needed local anesthesia. All treated digits healed without scarring in 2 weeks. Posttreatment biopsy in one patient showed normal epidermis and a slight fibrosis in the papillary dermis. Three patients remained free of recurrence (75%) at 15–17 months (average 16 months) after one treatment. One patient's BD recurred at 8 months, but was successfully treated without recurrence after 20 months. Conclusion. Our preliminary study suggests that PDT using 2% 5-ALA solution and an LED array is an effective, noninvasive method to treat digital BD with the benefit of scar-free contracture and loss of digital function. Among the various factors that would affect the results of PDT, we feel that partial removal of the thickened horny layer is the most important step to achieve sufficient therapeutic effect in digital BDs.

Background: The histogenesis of extramammary Paget’s disease (EMPD) is still controversial. Benign pagetoid cells of the nipple first described by Toker and the similar clear cells found in white maculopapules of clear cell papulosis (CCP) have been proposed to be potential precursor cells giving rise to EMPD and primary intraepidermal Paget’s disease in the nipple. The observation of a rare case of depigmented EMPD provided us with a chance to examine further the interesting Toker’s clear cell/CCP hypothesis. Methods: We performed pathologic studies, including Fontana-Masson stain and immunostaining for AE1/AE3 and S100P, on a new case of depigmented EMPD manifesting a 4×3 cm hypopigmented-depigmented patch on the root of the penis. Results: The lesion showed extensive intraepithelial proliferation of atypical pagetoid cells with markedly reduced epidermal melaninization but nearly normal numbers of melanocytes. The tumor cells were strongly positive for AE1/AE3 by immunostaining. Some tumor cells displayed tadpole-like morphology resembling the pagetoid cells of CCP. Such morphology was not observed in two random examples of non-depigmented genital EMPD. Conclusions: The findings of tadpole-shaped pagetoid cells and depigmentation in the present case suggest that depigmented EMPD may be histogenetically related to CCP. Depigmented EMPD should be considered in the differential diagnosis of vitiligo, depigmented mycosis fungoides and lichen sclerosus located along the milk line.

A 63-year-old retired male teacher presented with generalized pruritic papules for 4 years. The prurigo was recalcitrant to treatment and he was admitted for further evaluation and treatment. His medical history was significant for thyroidectomy for hyperthyroidism 23 years ago with normal thyroid function after surgery. He had hyperuricemia with gouty arthritis but received no treatment. He also complained of epigastric discomfort for several decades. He denied any history of atopy or drug allergies, and was not on medications before the onset of skin lesions. A blood examination showed peripheral eosinophilia (1040/mm 3 ). The serum IgE level was within the normal range. There was no hyperbilirubinemia. A stool examination showed no evidence of parasite infection. After discharge, he received treatment at other clinics in his hometown for 7 years. In 2001, he returned to our clinic because of worsening of the skin lesions. An examination revealed many lichenified and juicy papules disseminated on his trunk and extremities (Figures 1A–1C). A biopsy taken from a lichenoid papule showed compact hyperkeratosis, hypergranulosis, epidermal hyperplasia and fibrotic papillary dermis with dilated blood vessels, consistent with lichen simplex chronicus or prurigo histopathologically. The diagnosis of generalized prurigo nodularis was made. The prurigo showed a poor response to treatments, including topical high potency steroids, oral antihistamines and narrow band UVB phototherapy. New lesions continued to erupt despite 18 months of intensive treatments. Follow-up eosinophil counts were within normal limits. The patient finally gave up and declined further treatments. One year after giving up treatments for prurigo, he underwent an endoscopic retrograde cholangiopancreatography to evaluate his epigastric discomfort. It revealed a tumor at the ampulla of Vater, which was shown to be an adenoma pathologically (Figure 2A). Magnetic resonance imaging (Figure 2B) showed a tumor in the ampulla of Vater region. The patient had no signs of cholestasis. His serum levels of bilirubin, amylase and lipase were within the normal range. The tumor was excised and the final pathological diagnosis was villotubular adenoma with moderate dysplasia. Surprisingly, the prurigo showed spontaneous improvement and disappeared completely 2 years after an operation (Figures 3A–3C). He remained free of prurigo at 4 years follow-up.

In Hong Kong, the coming New Senior Secondary Information and Communication Technology (NSS ICT) curriculum highly emphasizes the complex thinking processes like creativity, critical thinking and problem solving. In this paper, we attempt to use two detailed examples to illustrate how to infuse problem solving skills into computer lessons. It means that classroom time can be spent on the thinking skill as well as on the curriculum content.

Information Technology (IT) has become pervasive in our society and it is playing an increasingly important role in education. There is a growing expectation that teachers will be able to make effective use of IT in all facets of their work in schools. There are at least two major reasons which underpin the need to prepare IT teachers in secondary schools. First, schools are expected to prepare students for future jobs. It is quite clear that most of the jobs of the future will require some knowledge of IT. It is therefore important that students learn about IT while they are in schools. This indicates that there is a great need for more teachers who are competent in IT. In particular, secondary schools are short of teachers who are capable of teaching IT as a subject and to incorporate the current learning theories into practice. Second, given the increasing deployment and application of IT in secondary schools, there will be a serious shortage of teachers who are capable of managing and coordinating the use of IT across the school in the secondary context. Under these circumstances, we are offering the IT major in the Postgraduate Diploma in Education (Secondary) (PGDE(S)) Programme in our Institute. The IT Major is designed to prepare university graduates in technology discipline to be able to act as competent IT subject teachers for all levels in Hong Kong secondary schools. This article will discuss the rationale, principles and approach in designing the programme.

Background: Wide excision or Mohs surgery is the standard treatment of skin squamous cell carcinoma (SCC). Superficial SCC or tumor smaller than 1 cm has been treated successfully with open spray cryosurgery. Larger tumor may not be as effective because tissue destruction is usually superficial. Intralesional cryosurgery (IC) may provide a deeper and better cell killing effect in larger tumors. We investigated the safety and efficacy of treating nodular SCC in 4 patients with IC. Methods: Four patients with nodular SCC/keratoacanthoma (tumor size, 1–2.5 cm, average 1.48 cm) on the face and extremity were treated with IC. An 18-ga needle was connected to a cryogun and inserted into the center of the tumor after local anesthesia. The tumors were treated with 2 freeze–thaw cycles with a 5- to 10-mm free margin. Additional IC or open spray cryosurgery was applied if residual tumor was noted during monthly follow-up. Results: No patient required analgesics or experienced wound infection after the procedures. After IC, all tumors reduced 40% to 75% in size within 1 week. Two patients received 1 additional spray cryosurgery. Complete remission was noted in all tumors (100%) in 2 months. No recurrence was noted during follow-up (average 5.1 years). All patients were satisfied with the results. Conclusion: Our observation suggests that IC can be simple and effective alternative treatment for SCC patients whose condition is not suitable for or who refused operation.

Glycogen synthase kinase-3 (GSK-3) facilitates interferon (IFN)-γ signaling. Because IFN-γ is involved in inflammatory skin diseases, such as psoriasis, the aim of this study was to investigate the pathogenic role of GSK-3 in 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced IFN-γ-mediated ear skin inflammation. TPA (3 μg per ear) induced acute skin inflammation in the ears of C57BL/6 mice, including edema, infiltration of granulocytes but not T cells, and IFN-γ receptor 1-mediated deregulation of intercellular adhesion molecule 1 (CD54). TPA/IFN-γ induced GSK-3 activation, which in turn activated signal transducer and activator of transcription 1. Inhibiting GSK-3 pharmacologically, by administering 6-bromoindirubin-3′-oxime (1.5 μg per ear), and genetically, with lentiviral-based short-hairpin RNA, reduced TPA-induced acute skin inflammation but not T-cell infiltration. It is noteworthy that inhibiting GSK-3 decreased TPA-induced IFN-γ production and the nuclear translocation of T-box transcription factor Tbx21, a transcription factor of IFN-γ, in CD3-positive T cells. In chronic TPA-induced skin inflammation, inhibiting GSK-3 attenuated epidermis hyperproliferation and dermis angiogenesis. These results demonstrate the dual role of GSK-3 in TPA-induced skin inflammation that is not only to facilitate IFN-γ signaling but also to regulate IFN-γ production. Inhibiting GSK-3 may be a potential treatment strategy for preventing such effects.

Worldwide, one in three cancers is skin-related, with increasing incidence in many populations. Here, we demonstrate the capacity of a DNAzyme-targeting c-jun mRNA, Dz13, to inhibit growth of two common skin cancer types-basal cell and squamous cell carcinomas-in a therapeutic setting with established tumors. Dz13 inhibited tumor growth in both immunodeficient and immunocompetent syngeneic mice and reduced lung nodule formation in a model of metastasis. In addition, Dz13 suppressed neovascularization in tumor-bearing mice and zebrafish and increased apoptosis of tumor cells. Dz13 inhibition of tumor growth, which required an intact catalytic domain, was due in part to the induction of tumor immunity. In a series of good laboratory practice-compliant toxicology studies in cynomolgus monkeys, minipigs, and rodents, the DNAzyme was found to be safe and well tolerated. It also did not interfere in more than 70 physiologically relevant in vitro bioassays, suggesting a reduced propensity for off-target effects. If these findings hold true in clinical trials, Dz13 may provide a safe, effective therapy for human skin cancer.