Search

Generalized pustular psoriasis (GPP) is a rare, potentially life-threatening skin disease characterized by relapsing and remitting flares of sterile neutrophilic pustules and systemic inflammation. The definition of GPP is inconsistent globally, with large discrepancies in clinical management. To provide clinical guidance on managing GPP, we conducted a systematic literature search for articles published within the last decade on PubMed and the Cochrane Library in October 2022 and held four consensus meetings with 12 Taiwanese dermatologists between October 2022 and July 2023. Upon review of 153 articles, we agreed to adopt the European Rare and Severe Psoriasis Expert Network GPP definition with additional clarifications on pustular flares in psoriatic plaques, circinate or annular lesions, and localized pustules. We also drafted a diagnostic algorithm to facilitate GPP diagnosis. Twenty-seven statements on GPP treatment reached consensus. We recommend using an oral retinoid or spesolimab injection for the first-line treatment in both acute (treating flares) and maintenance (preventing flares) settings in adults with GPP. For infants and juveniles with GPP, retinoids are recommended as a first-line treatment. Evidence for other conventional and investigational therapies was reviewed, and a treatment algorithm was proposed. We hope this consensus provides practical guidance for clinicians in Taiwan and helps improve outcomes for GPP patients.

Over the past few decades, immune checkpoint inhibitors (ICIs) have emerged as promising therapeutic options for the treatment of various cancers. These novel treatments effectively target key mediators of immune checkpoint pathways. Currently, ICIs primarily consist of monoclonal antibodies that specifically block cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed cell death 1 (PD-1), programmed cell death-ligand 1 (PD-L1), and lymphocyte activation gene 3 protein (LAG-3). Despite the notable efficacy of ICIs in cancer treatment, they can also trigger immune-related adverse events (irAEs), which present as autoimmune-like or inflammatory conditions. IrAEs have the potential to affect multiple organ systems, with cutaneous toxicities being the most commonly observed. Although cutaneous irAEs are typically of low-grade severity and can usually be managed effectively, there are cases where severe irAEs can become life-threatening. Therefore, early recognition and a comprehensive understanding of the mechanisms underlying cutaneous irAEs are crucial for improving clinical outcomes in cancer patients. However, the precise pathogenesis of cutaneous irAEs remains unclear. This review focuses on the skin manifestations induced by ICIs, the prognosis related to cutaneous irAEs, and the exploration of potential mechanisms involved in cutaneous irAEs.

Night shift workers have been associated with circadian dysregulation and metabolic disorders, which are tightly coevolved with gut microbiota. The chronic impacts of light-emitting diode (LED) lighting at night on gut microbiota and serum lipids were investigated. Male C57BL/6 mice were exposed to blue or white LED lighting at Zeitgeber time 13.5-14 (ZT; ZT0 is the onset of “lights on” and ZT12 is the “lights off” onset under 12-hour light, 12-hour dark schedule). After 33 weeks, only the high irradiance (7.2 J/cm2) of blue LED light reduced the alpha diversity of gut microbiota. The high irradiance of white LED light and the low irradiance (3.6 J/cm2) of both lights did not change microbial alpha diversity. However, the low irradiance, but not the high one, of both blue and white LED illuminations significantly increased serum total cholesterol (TCHO), but not triglyceride (TG). There was no significant difference of microbial abundance between two lights. The ratio of beneficial to harmful bacteria decreased at a low irradiance but increased at a high irradiance of blue light. Notably, this ratio was negatively correlated with serum TCHO but positively correlated with bile acid biosynthesis pathway. Therefore, chronic blue LED lighting at a high irradiance may harvest gut dysbiosis in association with decreased alpha diversity and the ratio of beneficial to harmful bacteria to specifically dysregulates TCHO metabolism in mice. Night shift workers are recommended to be avoid of blue LED lighting for a long and lasting time.

Shrimp allergy is a serious public health problem. Epidemiological studies indicated the main cause of food allergy is the ingestion of shrimp and crab. Consequently, reducing the risk of shrimp and crab allergy is a major research focus. Few studies have demonstrated the effect of enzyme hydrolysis on reduction of shrimp allergens in food. In this study, we used papain, a commonly used enzyme in the food industry, as an ingredient to decrease levels of allergen tropomyosin in shrimp. 0–50U of papain was used to treat the shrimp meat, and then heated to measure the levels of tropomyosin, and determined the change of the protein secondary structure. The results showed that 20U of papain decrease the tropomyosin levels up to 80 %, which was further enhanced when combined with 3 min of heating. Furthermore, the result of Fourier-transform infrared spectroscopy (FTIR) showed alteration of secondary protein structure after the processing. The processing developed in this study may be an effective method used to change the levels and structure of tropomyosin.

Hidradenitis suppurativa (HS), recognized as a chronic and debilitating skin disease, presents significant challenges in both diagnosis and treatment. This review explores the clinical manifestations, genetic landscape, and molecular mechanisms underlying HS. The disease’s association with a predisposing genetic background, obesity, smoking, and skin occlusion underscores the complexity of its etiology. Genetic heterogeneity manifests in sporadic, familial, and syndromic forms, with a focus on mutations in the γ-secretase complex genes, particularly NCSTN. The dysregulation of immune mediators, including TNF-α, IL-17, IL-1β, and IL-12/23, plays a crucial role in the chronic inflammatory nature of HS. Recent advancements in genetic research have identified potential therapeutic targets, leading to the development of anti-TNF-α, anti-IL-17, anti-IL-1α, and anti-IL-12/23 therapies and JAK inhibitors. These interventions offer promise in alleviating symptoms and improving the quality of life for HS patients.

Post-traumatic stress disorder (PTSD) is a psychiatric disorder that causes debilitating functional impairment in patients. Observations from survivors of traumatic historical events solidify that this disease is not only associated with personal experiences but can also be inherited from familial traumas. Over the past decades, researchers have focused on epigenetic inheritance to understand how responses to adverse experiences can be passed down to future generations. This review aims to present recent findings on epigenetic markers related to PTSD and research in the intergenerational inheritance of trauma. By understanding the information, we hope that epigenetic markers can act as biochemical measurements for future clinical practice.

Immune checkpoint inhibitors (ICIs) have emerged as novel options that are effective in treating various cancers. They are monoclonal antibodies that target cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed cell death 1 (PD-1), and programmed cell death-ligand 1 (PD-L1). However, activation of the immune systems through ICIs may concomitantly trigger a constellation of immunologic symptoms and signs, termed immune-related adverse events (irAEs), with the skin being the most commonly involved organ. The dermatologic toxicities are observed in nearly half of the patients treated with ICIs, mainly in the form of maculopapular rash and pruritus. In the majority of cases, these cutaneous irAEs are self-limiting and manageable, and continuation of the ICIs is possible. This review provides an overview of variable ICI-mediated dermatologic reactions and describes the clinical and histopathologic presentation. Early and accurate diagnosis, recognition of severe toxicities, and appropriate management are key goals to achieve the most favorable outcomes and quality of life in cancer patients.

Background: Psoriasis is a chronic inflammatory disease involving the skin and/or joints. Till 2016, there were five biologic agents for psoriatic arthritis treatment in Taiwan: etanercept, adalimumab, golimumab, ustekinumab, and secukinumab. Although European guidelines recommend tumor necrosis factor-α (TNF-α) inhibitors as the first-line biologic agents for axial disease of psoriatic arthritis, the drug survival of biologic agents in Asian populations remains unclear. Objectives: We investigated 5-year drug survival of biologic agents in patients with psoriatic arthritis. Methods: We used Kaohsiung Medical University Hospital Research Database to evaluate real-world 5-year drug survival of biologic agents for psoriatic arthritis in a medical center from southern Taiwan. Results: The 5-year drug survival rates of ustekinumab, etanercept, and adalimumab were significantly different. Ustekinumab and etanercept showed higher 5-year survival rates for psoriatic disease than adalimumab. Golimumab and secukinumab had a short follow-up time to obtain a conclusive 5-year survival rate. Conclusion: Considering that TNF-α inhibitors are often the first-line biologic agents for psoriatic arthritis in guidelines in western countries, the finding that ustekinumab is superior to TNF-α inhibitor adalimumab in terms of 5-year survival for psoriatic disease may imply that the therapeutic response of biologic agents may differ between different ethnic groups.

Background: Infection can upregulate T helper 17 (Th17) signaling and exacerbate psoriasis. Literature has indicated that prenatal infection induces embryonic development toward Th17 signaling and is a risk factor for developing certain Th17-skewing disorders such as autism in offspring. However, it remains unclear if a prenatal infection is a risk factor for developing psoriasis in offspring. Objectives: We investigated if a prenatal infection predisposes mice offspring to enhanced susceptibility to psoriatic inflammation. Methods: Pregnant C57BL/6 mice were intraperitoneally injected with lipopolysaccharide (LPS) or polyinosinic:polycytidylic acid poly I:C to simulate prenatal bacterial and viral infection, respectively. Phosphate-buffered saline (PBS) injection was used as the control. When mice offspring were at the age of 9–10 weeks, imiquimod (IMQ) cream or control vehicle was applied topically on ears for 5 consecutive days to induce psoriasiform dermatitis. The extent of epidermal hyperplasia and the number of Munro microabscesses were examined by histologic analysis. Protein expressions of neutrophil marker Ly6 g and Th17-associated cytokines were measured by western blotting. Results: Prenatal infection with LPS or poly I:C induced a greater extent of epidermal hyperplasia and more Munro microabscesses after IMQ application as compared with prenatal PBS injection. Mice offspring with prenatal infection also had higher protein expressions of Ly6 g, IL-17a, and interleukin-23 after IMQ stimulation compared with their PBS controls. Conclusion: Prenatal infection predisposes mice offspring to enhanced susceptibility to IMQ-mediated psoriasiform dermatitis. The data obtained from the present animal study suggest that prenatal infection might be a risk factor for developing psoriasis in offspring.

Abstract Exposure to arsenic, a ubiquitous metalloid on Earth, results in human cancers. Skin cancer is the most common arsenical cancers. Both autophagy and aquaporin pathway are known to promote carcinogenesis. However, the mechanisms by which arsenic regulates aquaporin and autophagy in arsenical skin cancers remain elusive. This study aims to address how arsenic regulates aquaporin-3, the predominant aquaporin in epidermal keratinocytes, and how this process would induce autophagy. Quantitative real-time PCR and immunofluorescence were used to measure the expression of aquaporin 3 in arsenical skin cancers and arsenic-treated keratinocytes. Beclin-1 expression and autophagy were measured. We examined if blocking aquaporin 3 could interfere arsenic-induced autophagy in keratinocytes. Expression of aquaporin 3 is increased in arsenical cancers and in arsenic-treated keratinocytes. Arsenic induced autophagy in primary human keratinocytes. Notably, the arsenic-induced autophagy was inhibited by pretreatment of keratinocytes with aquaporin inhibitors Auphen or AgNO3, or RNA interference against aquaporin 3. The data indicates that the aquaporin 3 is an important cell membrane channel to mediate arsenic uptake and contributes to the arsenic-induced autophagy.

Background: Psoriasis is a chronic inflammatory disease that affects the skin, joints, and cardiovascular system. Although a potential association of end-stage renal disease (ESRD) with psoriasis has been demonstrated in patients, the potential for the use of cyclosporin in these patients for the modulation of the course of ESRD remains doubted. Furthermore, the association between psoriasis and renal diseases in general remains unclear. This study aimed to investigate the risk of renal disease in psoriatic patients with or without the use of cyclosporin. Methods: We performed a retrospective cohort study using the National Health Insurance Database of Taiwan from 1996 to 2010 to identify patients with psoriasis, renal disease, chronic renal failure, and ESRD, and the use of cyclosporin. Overall, 3502 psoriatic patients and 10,506 matched population comparisons were identified. The hazard ratios (HRs) for renal events during the follow-up period were computed. Results: Patients with psoriasis had an increased risk of chronic renal failure [HR = 3.00; 95% confidence interval (CI), 2.30–3.93; p

Background/Objective: The prevalence of selected psychiatric disorders, such as depression and anxiety, is higher in patients with psoriasis. However, the association between psoriasis and schizophrenia is less clear. Here, we investigated whether the prevalence of schizophrenia is higher in patients with psoriasis. Methods: In this cross-sectional study, we analyzed the 1-million-person cohort enrolled from Taiwan's National Health Insurance Research Database. Psoriasis, schizophrenia, and comorbidities were ascertained by the International Classification of Diseases, 9th revision, Clinical Modification coding. For schizophrenia, the concomitant catastrophic illness certificate was used to verify the diagnosis. The prevalence of schizophrenia in patients with psoriasis was compared with the prevalence of schizophrenia in a comparable population using a generalized linear mixed model. Results: The prevalence of schizophrenia was significantly higher in patients with psoriasis than in the comparison population [prevalence ratio = 1.77, 95% confidence interval (CI) = 1.48–2.12, p

Blaschko lines are manifestations of cutaneous mosaicism, with apparent contrast between normal cells and abnormal cells, which carry postzygotic mutations. Linear cutaneous lupus erythematosus is a rare subset of cutaneous lupus erythematosus (CLE), characterized by skin lesions along Blaschko lines. In this paper, we presented a 47-year-old female with subacute CLE lesions along Blaschko lines. Although the antinuclear antibody and anti-Ro titers were remarkably high, there were no systemic symptoms. The histopathology showed atrophic epidermis with vacuolization of basal keratinocytes and papillary edema. While no typical linear lupus band was found, the direct immunofluorescence revealed cytoid bodies with immunoglobulin G, immunoglobulin M, C3, and C4 depositions in the papillary dermis. The skin lesions completely resolved after topical tacrolimus treatment, and the clinical course was 10 months without recurrence. We reviewed the literature and summarized that CLE along Blaschko lines supports the functional role of Ro antigens and keratinocytes in the development of CLE.

Abstract Objective Human placenta-derived exosomes (pExo) were generated, characterized, and evaluated as a therapeutic candidate for the treatment of osteoarthritis (OA). Methods pExo was generated from full-term human placenta tissues by sequential centrifugation, purification, and sterile filtration. Upon analysis of particle size, cytokine composition, and exosome marker expression, pExo was further tested in cell-based assays to examine its effects on human chondrocytes. In vivo therapeutic efficacies were evaluated in a medial meniscal tear/medial collateral ligament tear (MCLT + MMT) rat model, in which animals received pExo injections intraarticularly and weight bearing tests during in-life stage while histopathology and immunohistochemistry were performed as terminal endpoints. Results pExo displayed typical particle size, expressed maker proteins of exosome, and contained proteins with pro-proliferative, pro-anabolic, anti-catabolic, or anti-inflammatory activities. In vitro, pExo promoted chondrocyte migration and proliferation dose-dependently, which may involve its activation of cell growth-related signaling pathways. Expression of inflammatory and catabolic genes induced in a cellular OA model was significantly suppressed by pExo. In the rat OA model, pExo alleviated pain burden, restored cartilage degeneration, and downregulated expressions of pro-inflammatory, catabolic, or apoptotic proteins in a dose-dependent manner. Conclusions Our study demonstrates that pExo has multiple potential therapeutic effects including symptom control and disease modifying characteristics. This may make it an attractive candidate for further development as an anti-OA therapeutic.

The aim of this study is to evaluate the crown discoloration induced by bioceramic root canal filling materials (OrthoMTA and iRoot SP) compared to AH Plus. Material and Methods: Sixty intact mandibular single rooted premolars were sectioned 2 mm below the cemento-enamel junction, prepared, and randomly assigned into four groups according to the root filling materials: OrthoMTA, iRoot SP, AH Plus and unfilled.Results: Before placement of the materials in the pulp chamber and the coronal third of the root, the spectral reflectance lines of the crowns were recorded by a digital spectrophotometer at baseline, and after filling at 1 week and 1, 3 and 6 months and ∆Ε values were calculated. All materials used induced clinically perceptible crown discoloration (ΔΕ>3.7) and no significant difference was detected between these materials (p>0.05). Regardless of the material, discoloration progressed significantly within the three months (p

This paper presents the development of a custom SRAM island-style FPGA, covering the information needed and the steps involved in hardware implementation, bitstream configuration and design alternatives to facilitate the overall implementation effort from an academic point of view. To achieve the state of the art, commercial FPGAs can employ a large team, a high time-to-market, and high non-recurring engineering costs. In contrast, by taking the challenge of building a custom FPGA with a small team of researchers, the development of custom architecture and size focuses on the proof of concept. This baseline methodology result can be a start point for the development of new technologies or circuit enhancements.

In this paper, an architecture of an electrical equivalence pyranometer with analog control of the temperature difference is presented. The classical electrical equivalence pyranometer employs a Wheatstone bridge with a feedback amplifier to keep the sensor operating at a constant temperature to estimate the incident radiation through the sensor thermal balance employing the electrical equivalence principal. However, this architecture presents limitations under ambient temperature variation, such as sensitivity variation. To overcome those limitations, we propose an architecture that controls the temperature difference between the sensor and ambient via an analog compensating circuit. Analytical results show an improvement near five times in sensitivity over the ambient temperature span and 76.3% increase of useful output voltage. A prototype was developed and validated with a commercial pyranometer, showing a high agreement on the measurement results. It is verified that the use of temperature difference, rather than constant temperature, significantly reduces the effect of ambient temperature variation.

Water supply systems are constantly improving their operation through energy efficiency actions that involve the use of advanced measurement, control, and automation techniques. The maintenance and reliability of water distribution is directly associated with hydraulic pressure control. The main challenges encountered in hydraulic pressure control are associated with random changes in the supply plant and the presence of noise and outliers in the sensor measurements. These undesired characteristics cause inefficiency and instability in the control system of the pumping stations. In this scenario, this paper proposes an indirect adaptive control methodology by reference model for modeling and controlling water supply systems. The criterion adopted in the parametric estimation mechanism and the controller adaptation is the Maximum Correntropy. Experimental results obtained with an experimental bench plant showed that the maximum tracking error was 15% during demand variation, percentage overshoot less than 5%, and steady-state error less than 2%, and the control system became robust to noise and outliers. In comparison to the Mean Squared Error criterion, when noise and outliers influence the sensor signal, the proposed methodology stands out, reducing the mean error and the standard deviation, in the worst-case scenario, by more than 1500%. The proposed methodology, therefore, allows for increased reliability and efficiency of an advanced pump control system, avoiding downtime and equipment damage.