Advancing Treatment in Bullous Pemphigoid: A Comprehensive Review of Novel Therapeutic Targets and Approaches.

Bullous pemphigoid is one of the most common autoimmune bullous diseases occurring primarily in the elderly. Pathogenic autoantibodies against BP180 and BP230 at the dermal-epidermal junction cause subepidermal blisters, erosions, and intense pruritus, all of which adversely affect the patients' quality of life and may increase their morbidity and mortality. Current systemic treatment options for bullous pemphigoid are limited to corticosteroids and immunosuppressants, which can have substantial side effects on these vulnerable patients that even exceed their therapeutic benefits. Therefore, more precisely, targeting therapies to the pathogenic cells and molecules in bullous pemphigoid is an urgent issue. In this review, we describe the pathophysiology of bullous pemphigoid, focusing on autoantibodies, complements, eosinophils, neutrophils, proteases, and the T helper 2 and 17 axes since they are crucial in promoting proinflammatory environments. We also highlight the emerging therapeutic targets for bullous pemphigoid and their latest discoveries in clinical trials or experimental studies. Further well-designed studies are required to establish the efficacy and safety of these prospective therapeutic options.

Targeting type 2 inflammation in bullous pemphigoid: current and emerging therapeutic approaches.

Bullous pemphigoid (BP) is one of the most common autoimmune bullous diseases and mainly affects an elderly population with multi-morbidity. Due to the frailty of many BP patients, existing treatment options are limited. The blisters associated with BP result from IgG and IgE autoantibodies binding to the central components of hemidesmosome, BP180, and BP230, stimulating a destructive inflammatory process. The known characteristic features of BP, such as intense pruritus, urticarial prodrome, peripheral eosinophilia, elevated IgE, as well as recent expanding evidence from in vitro and in vivo studies implicate type 2 inflammation as an important driver of BP pathogenesis. Type 2 inflammation is an inflammatory pathway involving a subset of CD4+ T cells that secrete IL-4, IL-5, and IL-13, IgE-secreting B cells, and granulocytes, such as eosinophils, mast cells, and basophils. It is believed that effectors in type 2 inflammation may serve as novel and effective treatment targets for BP. This review focuses on recent understandings of BP pathogenesis with a particular emphasis on the role of type 2 inflammation. We summarize current clinical evidence of using rituximab (B-cell depletion), omalizumab (anti-IgE antibody), and dupilumab (anti-IL-4/13 antibody) in the treatment of BP. The latest advances in emerging targeted therapeutic approaches for BP treatment are also discussed.

Characterization of hemodialysis fistulas experienced abrupt thrombosis and determination of a proper follow-up protocol: A retrospective cohort study and an interventionist's perspective.

Abrupt thrombosis is a form of thrombosis that occurs unexpectedly and without being preceded by hemodialysis fistula (AVF) dysfunction during dialysis. We found that AVFs with a history of abrupt thrombosis (abtAVF) appeared to have more episodes of thrombosis and required more frequent interventions than those without such history. Therefore, we sought to characterize the abtAVFs and examined our follow-up protocols to determine which one is optimal. We performed a retrospective cohort study using routinely collected data. The thrombosis rate, AVF loss rate, thrombosis-free primary patency, and secondary patency were calculated. Additionally, the restenosis rates of the AVFs under the follow-up protocol/sub-protocols and the abtAVFs were determined. The thrombosis rate, procedure rate, AVF loss rate, thrombosis-free primary patency, and secondary patency of the abtAVFs were 0.237/pt-yr, 2.702/pt-yr, 0.027/pt-yr, 78.3%, and 96.0%, respectively. The restenosis rate for AVFs in the abtAVF group and the angiographic follow-up sub-protocol were similar. However, the abtAVF group had a significantly higher thrombosis rate and AVF loss rate than AVFs without a history of abrupt thrombosis (n-abtAVF). The lowest thrombosis rate was observed for n-abtAVFs, followed up periodically under the outpatient or angiographic sub-protocols. AVFs with a history of abrupt thrombosis had a high restenosis rate, and periodic angiographic follow-up with a mean interval of 3 months was presumed appropriate. For selected populations, such as salvage-challenging AVFs, periodic outpatient or angiographic follow-up was mandatory to extend their usable lives for hemodialysis.

Quantitative physical examination indicators to detect patients with stenosis at a high risk of thrombosis at hemodialysis vascular access sites: A retrospective case-control study.

BACKGROUND: Quantitative physical examination (PE) indicators, including palpable pulsatility length and outflow scores, can be used to quantify stenosis severity at hemodialysis vascular access sites. It is known that the risk of high-shear-related thrombosis is increased when the minimal luminal diameter (MLD) of stenosis decreases. At present, MLD is measured using sonography or angiography. This study sought to determine the relationship between quantitative PE indicators and MLD and report their diagnostic performance in detecting patients with stenosis at a high risk of thrombosis. METHODS: We performed a retrospective case-control study using routinely collected data. We used the post-stenosis palpable pulsatility length (sPPL) and pulse-and-thrill based outflow score to assess the severity of AVF inflow and outflow stenosis, respectively. We recorded paired quantitative PE indicators and MLD before and after angioplasty in patients enrolled over a 4-month period. RESULTS: A total of 249 paired PE indicators and MLD measurements were obtained from 163 patients. A receiver operating characteristic curve analysis showed that an MLD cutoff value of <1.55 mm and an MLD of <1.95 mm discriminated sPPL = 0 and PESOS (physical examination significant outflow stenosis)/1- of the outflow score, respectively, from all other measurements, with the area under the curve values of 0.8922 and 0.9618, respectively. With sPPL = 0 and PESOS/1- of the outflow score as diagnostic tools to detect inflow stenosis with an MLD of ⩽1.5 mm and outflow stenosis with an MLD of ⩽1.9 mm at vascular access sites, sensitivity = 86.00% and 88.46%; specificity = 97.67% and 92.11%; positive predictive values of 97.73% and 92.00% and negative predictive values of 85.71% and 88.61%, respectively, were observed. CONCLUSIONS: Our preliminary results showed that physical examination can potentially be a diagnostic tool in detecting patients with stenosis who are at a high risk of thrombosis at hemodialysis vascular access sites with high diagnostic accuracy.

Taiwanese dermatological association (TDA) consensus for the management of pemphigus.

Pemphigus is an uncommon but life-threatening autoimmune blistering disease characterized by the presence of antibodies against desmogleins. Without effective treatment, pemphigus can result in significant morbidity and mortality. Existing consensus statements on pemphigus management from international medical groups provide varying guidelines, especially on treatment. Thus, on January 4, 2020, a panel of seven dermatology experts from the Taiwanese Dermatological Association (TDA) and one rheumatology expert convened to develop a consensus for the management of pemphigus. These experts with extensive experience in pemphigus management were recommended by their respective teaching hospitals and primary care clinics in Taiwan and by the TDA. The meeting reviewed the available consensus statements from international dermatology groups, including the European Dermatology Forum (EDF), the European Academy of Dermatology and Venereology (EADV), and the International Bullous Diseases Consensus Group. Using these guidelines as a basis for discussion and consensus formulation, these experts formulated their consensus statement that provides practical, concise but comprehensive recommendations as to the diagnosis, treatment, and monitoring of pemphigus patients in Taiwan. This consensus serves as a clinical reference for physicians for the management of pemphigus in Taiwan or wherever it may be applicable.

Efficacy of Dupilumab on Different Phenotypes of Adult with Moderate-to-Severe Atopic Dermatitis in Taiwan: A Real-World Study.

To determine phenotype-related dupilumab response in adult patients with atopic dermatitis (AD), this multicenter, retrospective study included 111 adults with moderate-to-severe AD in Taiwan, with median age of 31.5 years (18-87) and 71 (64.0%) males. Patients received dupilumab 300 mg per two to three weeks up to 12 months. We found a significant improvement after 4 and 16 weeks of treatment in all patients for all the assessed scores, including eczema area and severity index (EASI) improvement ≥50% (EASI-50) and 75% (EASI-75), EASI reaching minimal clinically important difference (MCID), and Investigator's Global Assessment (IGA) improvement ≥2. Importantly, prior to asthma, early AD onset and 3-week drug intervals were significantly associated with a high proportion of EASI-75 at month 12, while prurigo and lichenoid phenotypes were associated with a lower proportion of EASI-75 at month 12. However, the majority of adverse events were mild in severity. In conclusion, our study results identify phenotype-related dupilumab response at month 12 in adults with moderate-to-severe AD, and we suggest that treatment should not be discontinued until reaching a satisfactory clinical response.

Increased HIF-1α expression in T cells and associated with enhanced Th17 pathway in systemic lupus erythematosus.

BACKGROUND/PURPOSE: Recent emerging evidence indicates that dysfunction of metabolic remodeling underlies aberrant T cell immune responses in systemic lupus erythematosus (SLE). This study was undertaken to investigate the expression of HIF-1α, a regulator of metabolic reprogramming, in T cells from SLE. METHODS: HIF-1α expression in T lymphocytes from SLE patients was examined by quantitative polymerase chain reaction (PCR) and the protein expression was analyzed with intracellular staining in flow cytometry. HIF-1α was overexpressed in murine CD4 T cells via transducing T cells with HIF-1α containing lentivirus. The expression of HIF-1α, metabolic- and Th17-associated genes in T cells from SLE patients and its association with clinical manifestation was analyzed. RESULTS: HIF-1α expression is increased in CD4 T cells from SLE patients both in intracellular staining and quantitative PCR analysis. In addition, there is enhanced HIF-1α expression in Th17-skewing murine T cells, and lentivirus-mediated HIF-1α overexpression promotes Th17 differentiation. Moreover, HIF-1α gene expression is positively correlated with the expression of glycolysis- and IL-17-associated genes in SLE patients. CONCLUSION: HIF-1α expression is increased in T cells from SLE patients, and is positively correlated with glycolysis- and Th17- associated pathway, implicating HIF-1α contributes to the activation of Th17 cells in SLE, and represents a potential novel therapeutic target.

Advances in Research on Stem Cell-Based Pulp Regeneration.

Although root canal therapy is the most common and widely used treatment at clinical presentation, there are still some postoperative complications. As cell biology and tissue engineering techniques advance rapidly, the use of biological therapy to regenerate dental pulp has become a new trend; Relevant literatures in recent five years were searched using key words such as "root canal therapy", "Dental pulp stem cells", "Dental pulp regeneration", and "Cell homing" in PubMed, Web of Science, etc; Dental pulp stem cells (DPSCs) have multi-differentiation potential, self-renewal capability, and high proliferative ability. Stem cell-based dental pulp regeneration has emerged as a new research hot spot in clinical therapy. Recently, dental pulp-like structures have been generated by the transplantation of exogenous DPSCs or the induction of homing of endogenous DPSCs. Studies on DPSCs are important and significant for dental pulp regeneration and dental restoration; In this review, the existing clinical treatment methods, dental pulp regeneration, and DPSC research status are revealed, and their application prospects are discussed. The stem cell-based pulp regeneration exerts promising potential in clinical therapy for pulp regeneration.

Detecting Lesional Granulysin Levels for Rapid Diagnosis of Cytotoxic T lymphocyte-Mediated Bullous Skin Disorders.

BACKGROUND: Bullous skin disorders are induced by different pathomechanisms and several are emergent, including Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). Rapid diagnostic methods for SJS/TEN or cytotoxic T-lymphocyte (CTL)-mediated bullous disorders are crucial for early treatment. Granulysin, primarily expressed by CTLs, is a specific cytotoxic protein responsible for SJS/TEN and similar skin reactions. OBJECTIVE: To assess granulysin levels in blister fluids to differentiate SJS/TEN and similar CTL-mediated bullous reactions from other autoimmune bullous disorders. METHODS: Using ELISA, we measured granulysin in blister fluids from patients with bullous skin disorders, including SJS/TEN, erythema multiforme major, bullous fixed-drug eruption, bullous lupus erythematosus, paraneoplastic pemphigus, pemphigus vulgaris, bullous pemphigoid, purpura fulminans-related bullae, and hand-foot syndrome/hand-foot-skin reactions. We compared serum and blister granulysin levels in patients with SJS/TEN presenting varying severity, monitoring serial granulysin levels from acute to late stages. RESULTS: Overall, 144 patients presenting with bullous skin disorders were enrolled. Blister granulysin levels (mean ± SD) in CTL-mediated disorders, including TEN (n = 28; 3938.7 ± 3475.7), SJS-TEN overlapping (n = 22; 1440.4 ± 1179.6), SJS (n = 14; 542.0 ± 503.2), erythema multiforme major (n = 7; 766.3 ± 1073.7), generalized bullous fixed-drug eruption (n = 10; 720.4 ± 858.3), and localized bullous fixed-drug eruption (n = 16; 69.0 ± 56.4), were significantly higher than in non-CTL-mediated bullous disorders (P < .0001), including bullous lupus erythematosus (n = 3; 22.7 ± 20.1), paraneoplastic pemphigus (n = 3; 20.3 ± 8.6), pemphigus vulgaris (n = 3; 4.4 ± 2.8), bullous pemphigoid (n = 18; 4.0 ± 2.7), purpura fulminans (n = 4; 5.9 ± 5.5), and hand-foot syndrome/hand-foot-skin reactions (n = 6; 4.6 ± 3.5). Blister granulysin levels correlated with clinical severity of SJS/TEN (P < .0001). CONCLUSIONS: Determination of blister granulysin levels is a noninvasive and useful tool for rapid differential diagnosis of SJS/TEN and other similar CTL-mediated bullous skin disorders for treatment selection.

Different impacts of various tocolytic agents on increased risk of postoperative hemorrhage in preterm labor women undergoing Cesarean delivery: A population-based cohort study.

Tocolytic agents, commonly used for inhibiting preterm labor, pose the risk of uterine atony, leading to postpartum hemorrhage. This study elucidated the effects of different tocolytic agents on postoperative hemorrhage among women in preterm labor undergoing Cesarean delivery (CD). Data from Taiwan National Health Insurance Research Database were analyzed. The risk (adjusted hazard ratio [aHR] and 95% confidence intervals [CI]) of postoperative hemorrhage in CD women with preterm labor diagnosis using tocolytic agents (Tocolysis group) comparing to CD women not using tocolytic agents (Control group) were determined. Impacts of different tocolytic agents in this regard were also investigated. Our data revealed that the incidence (11.7% vs 2.6%, P < .001) and risk (aHR: 1.21, 95% CI: 1.12-1.31, P < .001) of postoperative hemorrhage were significantly higher in the Tocolysis group (n = 15,317) than in the Control group (n = 244,096). Ritodrine was the most frequently used tocolytic agent (80.5%), followed by combination therapy (using more than one tocolytic agents) (8.5%), magnesium sulfate (MgSO4, 4.6%), calcium channel blockers (3.8%), betamimetics other than ritodrine (1.9%), prostaglandin synthase inhibitors (0.5%), and nitrates (0.1%). Barring those using calcium channel blockers and combination therapy, the use of MgSO4 (aHR: 1.43, P = .001), betamimetics other than ritodrine (aHR: 1.71, P < .001), prostaglandin synthase inhibitors (aHR: 2.67, P < .001) and nitrates (aHR: 3.30, P = .001) was associated with higher risks of postoperative hemorrhage compared with ritodrine. In conclusion, CD women with preterm labor diagnosis using tocolytic agents exhibit an increased risk of postoperative hemorrhage and that this risk varies with the use of different tocolytic agents.

Gapless spin liquid in a square-kagome lattice antiferromagnet.

Observation of a quantum spin liquid (QSL) state is one of the most important goals in condensed-matter physics, as well as the development of new spintronic devices that support next-generation industries. The QSL in two dimensional quantum spin systems is expected to be due to geometrical magnetic frustration, and thus a kagome-based lattice is the most probable playground for QSL. Here, we report the first experimental results of the QSL state on a square-kagome quantum antiferromagnet, KCu6AlBiO4(SO4)5Cl. Comprehensive experimental studies via magnetic susceptibility, magnetisation, heat capacity, muon spin relaxation (µSR), and inelastic neutron scattering (INS) measurements reveal the formation of a gapless QSL at very low temperatures close to the ground state. The QSL behavior cannot be explained fully by a frustrated Heisenberg model with nearest-neighbor exchange interactions, providing a theoretical challenge to unveil the nature of the QSL state.

NanoMuscle: controllable contraction and extension of mechanically interlocked DNA origami.

Artificial molecular machines synthesized in supramolecular chemistry have attracted great interest over the past decades. DNA origami presents an alternative approach to construct nano-machines by directly designing its thermodynamically stable state by DNA sequences. Here, we construct a molecular device, named NanoMuscle, with mechanically interlocked DNA origami. NanoMuscle's configuration - either extended or contracted - can be controlled by adding specific DNA strands. We monitored NanoMuscle's multistep synthesis with gel electrophoresis, and verified that monomers of the NanoMuscle are interlocked at correct orientation with transmission electron microscopy (TEM). We then validated that NanoMuscle can switch between extended and contracted configuration. By converting binding energy from DNA hybridization and Brownian motion to mechanical movements, NanoMuscle may serve as a novel building block for future mesoscale machinery.

The interaction-induced dipole of H2-H: New ab initio results and spherical tensor analysis.

We present numerical results for the dipole induced by interactions between a hydrogen molecule and a hydrogen atom, obtained from finite-field calculations in an aug-cc-pV5Z basis at the unrestricted coupled-cluster level including all single and double excitations in the exponential operator applied to a restricted Hartree-Fock reference state, with the triple excitations treated perturbatively, i.e., UCCSD(T) level. The Cartesian components of the dipole have been computed for nine different bond lengths r of H2 ranging from 0.942 a.u. to 2.801 a.u., for 16 different separations R between the centers of mass of H2 and H between 3.0 a.u. and 10.0 a.u., and for 19 angles θ between the H2 bond vector r and the vector R from the H2 center of mass to the nucleus of the H atom, ranging from 0° to 90° in intervals of 5°. We have expanded the interaction-induced dipole as a series in the spherical harmonics of the orientation angles of the H2 bond axis and of the intermolecular vector, with coefficients DλL(r, R). For the geometrical configurations that we have studied in this work, the most important coefficients DλL(r, R) in the series expansion are D01(r, R), D21(r, R), D23(r, R), D43(r, R), and D45(r, R). We show that the ab initio results for D23(r, R) and D45(r, R) converge to the classical induction forms at large R. The convergence of D45(r, R) to the hexadecapolar induction form is demonstrated for the first time. Close agreement between the long-range ab initio values of D01(r0 = 1.449 a.u., R) and the known analytical values due to van der Waals dispersion and back induction is also demonstrated for the first time. At shorter range, D01(r, R) characterizes isotropic overlap and exchange effects, as well as dispersion. The coefficients D21(r, R) and D43(r, R) represent anisotropic overlap effects. Our results for the DλL(r, R) coefficients are useful for calculations of the line shapes for collision-induced absorption and collision-induced emission in the infrared and far-infrared by gas mixtures containing both H2 molecules and H atoms.

A sublimate sorbent for stir-bar sorptive extraction of aqueous endocrine disruptor pesticides for gas chromatography-electron capture detection.

A dumbbell-shaped magnetic stir-bar with sublimate sorbent was prepared for the stir bar sorptive extraction (SBSE) of pesticides in an aqueous sample prior to gas chromatography-micro-electron capture detection (GC-µECD). Cyclododecane (CDD) was coated onto a magnetic stir-bar surface as a sublimate sorbent, and steel balls were placed on both ends to form a dumbbell-shaped magnetic stir-bar for SBSE. Four EDC pesticides including chlorpyrifos, ethion, bromopropylate, and λ-cyhalothrin in aqueous samples were selected as model species to examine the proposed SBSE and the following desorption. The parameters studied were those affecting the extraction efficiencies including the coating (solvent for CDD and thickness), extraction (sample pH, stirring rate, time, and salting out effect), dissolution solvent volume, and the loss of CDD sublimated in air. The maximum extraction efficiency was obtained under the following conditions. The stir bar (with CDD thickness of 5.2 µm) was added into a 10 mL sample solution (at pH 7) for a 20-min extraction at 600 rpm. Then, the stir bar was gently removed from the sample solution, disassembled, and immersed into a 0.2 mL insert tube consisting of 3 µL hexane to dissolve; 1 µL was used for GC-ECD analysis. The linear ranges were 0.005-5 µg L-1 with coefficients of determination ranging from 0.9950 - 0.9994. Detection limits (based on S/N = 3) of the four EDCs were 0.4-4.5 ngL-1 with a relative standard deviation (RSD) of 2.4-6.3%, and quantitation limits (based on S/N = 5) were 1-15 ngL-1. The relative recoveries of the spiked samples were in the range of 83.2-98.7% with RSDs of 2.1-8.4% in farm field waters. The proposed sublimation sorbent obtained excellent enrichment factors (101-834) and provided a simple, rapid, sensitive, and eco-friendly sample preparation method.

The Function of HLA-B*13:01 Involved in the Pathomechanism of Dapsone-Induced Severe Cutaneous Adverse Reactions.

Dapsone-induced hypersensitivity reactions may cause severe cutaneous adverse reactions, such as drug reaction with eosinophilia and systemic symptoms (DRESS). It has been reported that HLA-B*13:01 is strongly associated with dapsone-induced hypersensitivity reactions among leprosy patients. However, the phenotype specificity and detailed immune mechanism of HLA-B*13:01 remain unclear. We investigated the genetic predisposition, HLA-B*13:01 function, and cytotoxic T cells involved in the pathogenesis of dapsone-induced severe cutaneous adverse reactions. We enrolled patients from Taiwan and Malaysia with DRESS and maculopapular eruption with chronic inflammatory dermatoses. Our results showed that the HLA-B*13:01 allele was present in 85.7% (6/7) of patients with dapsone DRESS (odds ratio = 49.64, 95% confidence interval = 5.89-418.13; corrected P = 2.92 × 10-4) but in only 10.8% (73/677) of general population control individuals in Taiwan. The level of granulysin, the severe cutaneous adverse reaction-specific cytotoxic protein released from cytotoxic T cells, was increased in both the plasma of DRESS patients (36.14 ± 9.02 ng/ml, P < 0.05) and in vitro lymphocyte activation test (71.4%, 5/7 patients) compared with healthy control individuals. Furthermore, dapsone-specific cytotoxic T cells were significantly activated when co-cultured with HLA-B*13:01-expressing antigen presenting cells in the presence of dapsone (3.9-fold increase, compared with cells with no HLA-B*13:01 expression; P < 0.01). This study indicates that HLA-B*13:01 is strongly associated with dapsone DRESS and describes a functional role for the HLA-restricted immune mechanism induced by dapsone.

Microwave-assisted decomplexation and in-situ headspace in-syringe dynamic derivatization of dimethylamine borane with high performance liquid chromatography-fluorescence detection.

A rapid, sensitive, selective, and simple method for monitoring dimethylamine borane (DMAB) in aqueous sample is proposed by combining microwave-assisted de-complexation, headspace liquid phase in-situ derivatization extraction, and high-performance liquid chromatography-fluorescence detection for the determination of DMAB in samples. The present procedure involves de-complexation of DMAB using microwave irradiation, evolution of dimethylamine (DMA) to the headspace from an alkalized sample solution, and dynamic headspace liquid-phase derivatization extraction (Dy-HS-LPDE) of DMA with 9-fluorenylmethyl chloroformate in a syringe barrel. In addition to the optimal Dy-HS-LPDE and chromatographic parameters described in our previous study, the de-complexation of DMAB by thermal and microwave-assisted procedures and evolution of DMA into the headspace from an alkalized solution and modification of the Dy-HS-LPDE method are thoroughly investigated. The results indicate that complete de-complexation was obtained at 70 °C for 5 min, 30 °C for 10 min, or using microwave irradiation for 30 s at any applied power. It indicates that the DMAB complex easily undergoes de-complexation under microwave irradiation. The linearity range was 0.01-0.5 mg L-1 for DMAB and 0.0077-0.38 mg L-1 for DMA, with a coefficient of determination of 0.9995, and limit of detection of 3 µg L-1 (limit of quantitation of 10 µg L-1) for DMAB. The recoveries of DMAB are 95.3% (3.0% RSD) for waste water when spiked 0.05 mg L-1 and 93.5% (5.4% RSD) for the samples spiked with copper and nickel salts (5 mM each in the spiked waste sample). The whole analytical procedure can be completed within 25 min. The results confirm that the present method is a rapid, sensitive, selective, automated, low-cost and eco-friendly procedure to identify DMAB in samples.

Urinary incontinence in female outpatients in Singapore.

INTRODUCTION AND HYPOTHESIS: The aims of this study were to determine the prevalence, symptom characteristics, risk factors and impact on quality of life (QoL) of urinary incontinence (UI) in female outpatients in Singapore, to describe the attitudes of these women towards UI, and to investigate the barriers to healthcare-seeking behaviour in symptomatic women. METHODS: This was a cross-sectional study in a convenience sample and 249 women enrolled from outpatient clinics. A modified self-administered questionnaire which included two validated instruments (the International Consultation on Incontinence Questionnaire-Urinary Incontinence short form and the Incontinence Impact Questionnaire-7) was used. RESULTS: Questionnaires from 230 women were included in the analysis. The overall prevalence of UI was 41.74% (95% CI 35.49-48.26%). Most of the symptomatic women suffered from mild UI and the most common subtype was stress UI. Age (OR 1.03, 95% CI 1.00-1.05), vaginal delivery (OR 2.67, 95% CI 1.43-4.97) and being sexually active (OR 2.41, 95% CI 1.31-4.43) were associated with UI. Among symptomatic women, only 41.25% (95% CI 30.82-52.53%) had sought medical attention before. The most common barrier to healthcare-seeking behaviour was embarrassment. The median QoL score was 33.33, indicating a mild impact of UI on QoL. QoL score was associated with UI severity (p < 0.001). CONCLUSIONS: Despite the high prevalence of UI, only about 41% of UI sufferers had sought medical attention before. Common barriers included embarrassment, fear of surgery and misconceptions. This study emphasizes the need for policy development for UI prevention and management in Singapore.

Chromoblastomycosis in Taiwan: A report of 30 cases and a review of the literature.

Chromoblastomycosis (CBM) is an implantation mycosis characterized by the presence of pigmented muriform cells in tissue. CBM is endemic in Taiwan, but only three formal cases have been reported to date because of underreporting. To describe and update its epidemiologic features, we report a series of 30 cases between 2003 and 2016 at a single medical center. Patients were predominately male (2.75:1). The mean age of onset was 65.9 years, and disease duration ranged from 2 months to 20 years. Diabetes was the most common comorbidity, and extremities were the most frequent sites of involvement. The lesions presented as papuloplaque, verrucous, cicatricial, targetoid, or mixed types. The dermoscopic features were variable, including red dots, white vague areas, black globules, and sand-like patterns. Among 10 Fonsecaea isolates further identified by sequencing the ITS regions of ribosomal DNA, nine were F. monophora and one was F. nubica. All but one patient received either systemic antifungal agents, surgical excision, or both. Surgical excision achieved a higher complete remission rate than the other forms of treatment did.

Nonlinear electrocardiographic imaging using polynomial approximation networks.

Electrocardiography is a valuable tool to aid in medical understanding and treatment of heart-related ailments, specifically atrial fibrillation (AF) and other irregular cardiac behavior. Although signs of AF will manifest in conventional electrocardiogram (ECG) recordings, interpretation and localization of AF sources require significant clinical expertise. In this vein, electrocardiographic imaging has emerged as an important medical imaging modality that provides reconstructions of the heart's electrical activity from non-invasive multi-lead body-surface ECG and anatomical x-ray computed tomography images. In this paper, we present a nonlinear inversion model for computing this mapping to improve upon the reconstruction performance of current methods. While contemporary techniques typically determine an inverse solution by discretizing and inverting an underdetermined linear system of partial differential equations governing the relationship between voltage potentials of the heart and torso, the presented technique re-casts this problem as a task in function approximation and provides a direct parameterization of the inverse operator using a polynomial neural network. That is, the outlined nonlinear inversion technique is a generalization of contemporary reconstruction techniques which allows geometrical and material parameterizations of the forward-model to be optimized using real experimental data collected from patients suffering from AF, as to better represent the inverse operator with respect to reconstruction metrics applicable to electrophysiology. The accuracy of our model is evaluated against a dataset of real-patient recordings to demonstrate its validity, and mathematical analysis is provided to support the polynomial expansion used in our inversion model.

CTHRC1 activates pro-tumorigenic signaling pathways in hepatocellular carcinoma.

CTHRC1 expression is involved in invasion and metastasis in various tumors. However, the molecules involved in its signaling pathways in hepatocellular carcinoma (HCC) remain elusive. The migration and invasion abilities of HCC cells stably expressing CTHRC1 were assessed in vitro and in vivo with a mouse model. Moreover, signaling pathways involved in invasion and metastasis were analyzed. CTHRC1 was abundantly expressed in HCC cell lines and HCC tissues. CTHRC1 was also detectable in the serum of HCC patients, compared with non-tumor controls. CTHRC1 mRNA was positively correlated with large tumor size (p <0.003), Edmondson differentiation grade (p <0.0001), microvessel invasion (p <0.05), intrahepatic metastasis (p <0.005), and HCC stage (AJCC, p <0.0001). Ectopic expression of CTHRC1 in HepG2 cells promoted cell migration and invasiveness in vitro, and promoted tumor metastasis in a lung metastasis mouse model. Knockdown of CTHRC1 by short hairpin RNA (shRNA) in HCC cells suppressed migratory and invasive abilities. Growth factor-mediated CTHRC1 expression promoted cancer cell invasiveness and metastasis through activation of CREB/Snail signaling, which induced EMT change and MMPs expression. Therefore, CTHRC1 and its downstream molecules may be potential therapeutic targets for HCC invasion and metastasis.