The evaluation of synchronous and asynchronous online learning: student experience, learning outcomes, and cognitive load.

BACKGROUND: The abrupt onset of the COVID-19 pandemic compelled universities to swiftly establish online teaching and learning environments that were not only immediately deployable but also conducive to high-quality education. This study aimed to compare the effectiveness of the online synchronous and asynchronous teaching formats in the dermatology lecture for undergraduate medical students, including academic performance, self-efficacy, and cognitive load. METHODS: A total of 170 fourth-year undergraduate medical students attending the dermatology lecture were included. The lecture was delivered using both the synchronous method (live online lecture via Webex meeting) and the asynchronous method (lecture videos shared on YouTube). The students had the freedom to choose their preferred method of attending the online lecture. The study assessed three main aspects: (1) learning outcomes measured through pretest, posttest, and retention test scores; (2) cognitive load experienced by students, including mental load and mental effort measured using eight items; and (3) satisfaction levels with each online teaching format. RESULTS: In this study, 70 students opted for the synchronous online lecture, while 100 students chose the asynchronous online lecture. Both synchronous and asynchronous teaching methods exhibited significant improvements in post and retention test scores compared to the pretest. Satisfaction levels, rated on a scale of 0-5, were generally high for both teaching methods, with no significant differences observed (4.6 for synchronous, 4.53 for asynchronous; p =.350). Regarding cognitive load, the synchronous method showed a significantly lower level than the asynchronous method (p =.0001). Subgroup analysis revealed no difference in mental effort (p =.0662), but the level of mental load was lower in the synchronous method (p =.0005). CONCLUSIONS: Both synchronous and asynchronous online teaching methods demonstrated improvements in learning outcomes and high levels of student satisfaction. However, the cognitive load experienced by students was lower in the synchronous setting compared to the asynchronous setting. These findings remind health professions educators that they would consider the students' cognitive load when designing online curricula.

Loss of GPNMB Causes Autosomal-Recessive Amyloidosis Cutis Dyschromica in Humans.

Amyloidosis cutis dyschromica (ACD) is a distinct form of primary cutaneous amyloidosis characterized by generalized hyperpigmentation mottled with small hypopigmented macules on the trunks and limbs. Affected families and sporadic case subjects have been reported predominantly in East and Southeast Asian ethnicities; however, the genetic cause has not been elucidated. We report here that the compound heterozygosity or homozygosity of GPNMB truncating alleles is the cause of autosomal-recessive ACD. Six nonsense or frameshift mutations were identified in nine individuals diagnosed with ACD. Immunofluorescence analysis of skin biopsies showed that GPNMB is expressed in all epidermal cells, with the highest staining observed in melanocytes. GPNMB staining is significantly reduced in the lesional skin of affected individuals. Hyperpigmented lesions exhibited significantly increased amounts of DNA/keratin-positive amyloid deposits in the papillary dermis and infiltrating macrophages compared with hypo- or depigmented macules. Depigmentation of the lesions was attributable to loss of melanocytes. Intracytoplasmic fibrillary aggregates were observed in keratinocytes scattered in the lesional epidermis. Thus, our analysis indicates that loss of GPNMB, which has been implicated in melanosome formation, autophagy, phagocytosis, tissue repair, and negative regulation of inflammation, underlies autosomal-recessive ACD and provides insights into the etiology of amyloidosis and pigment dyschromia.

Filler migration to the forehead due to multiple filler injections in a patient addicted to cosmetic fillers.

Filler migration is a potential complication following the injection of multiple fillers. With the increasing popularity of multiple filler injections, migrated granulomas should be an essential differential diagnosis for newly growing facial lumps. It is important for all physicians to be aware that complication induced by dermal fillers can occur in locations other than the planned injected sites. We described a case of filler migration to the forehead in a patient addicted to cosmetic fillers. To our knowledge, it has never been published in dermatology literature so far. A detailed history of cosmetic procedures from the patient addicted to filler injections is necessary for accurate diagnosis. Because account of previous cosmetic filler injections is not always reliable, an early skin biopsy with pathological examination is the gold standard for determining whether multiple filler injections have been performed.

Ethanol-metabolizing activities and isozyme protein contents of alcohol and aldehyde dehydrogenases in human liver: phenotypic traits of the ADH1B*2 and ALDH2*2 variant gene alleles.

OBJECTIVE: Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) are principal enzymes responsible for the metabolism of ethanol. East Asian populations are unique in that they carry both a prevalent ADH1B*2 and a dominant-negative ALDH2*2 allele. A systematic investigation of ethanol-metabolizing activities in normal livers correlated with the corresponding functional allelic variations and protein contents of the relevant isozymes in respective enzyme families has been lacking. MATERIALS AND METHODS: To obtain a reasonable sample size encompassing all possible genetic allelotypes of the ADH1B and ALDH2, 141 surgical liver specimens from adult Han Chinese were studied. Expression patterns and activities of ADH and ALDH were determined with stratification of the genetic phenotypes. Absolute protein contents as well as cellular localization of the activity and protein of ADH/ALDH isozymes were also investigated. RESULTS: The activities of ADH1B*1/*2 and ADH1B*2/*2 allelic phenotypes were 5-6-fold those of the ADH1B*1/*1, suggesting that ADH1B*2 allele-encoded subunits are dominant over expression of hepatic ADH activity. The activities of the ALDH2-active phenotype were 90% higher than those of the ALDH2-inactive phenotype. Sex and age did not significantly influence the hepatic ADH and ALDH activities with specified genetic phenotypes. The isozyme protein contents were as follows in decreasing order: ADH1, ADH2, ALDH1A1, ALDH2, and ADH3. Both ADH1, but not ADH2/3, and ALDH1A1/2 showed a preferential expression in perivenular hepatocytes. CONCLUSION: Functional correlations of ADH1B*2 and ALDH2*2 variant alleles in the liver provide a biochemical genetic basis suggesting their contribution toward variability in ethanol metabolism as well as susceptibility to alcoholism and alcohol-related diseases in East Asians.

Dominance of the inactive Asian variant over activity and protein contents of mitochondrial aldehyde dehydrogenase 2 in human liver.

BACKGROUND: It has been well documented that a variant allele of mitochondrial aldehyde dehydrogenase 2 (ALDH2), ALDH2*2, commonly occurs in East Asians but rarely in other ethnic populations. This unique allelic variation significantly influences drinking behavior and susceptibility to development of alcoholism. Previous structural, functional, and cellular studies indicate that the resulting variant polypeptide subunit K (Lys-487) exerts dominance of null activity and shorter half-life over the tetrameric enzyme molecules in distinct manners. However, the in vivo evidence for the proposed dominance mechanisms remains lacking. METHODS: To address this question, we investigated 33 surgical liver samples identified to be normal homozygous ALDH2*1/*1 (n = 17), heterozygous ALDH2*1/*2 (n = 13), and variant homozygous ALDH2*2/*2 (n = 3). The ALDH2 activity was determined at a sufficient low acetaldehyde concentration (3 µM) and the isozyme protein amount by immunotitration using purified class-specific antibodies. RESULTS: The tissue ALDH2 activity in heterozygotes was 17% that of the ALDH2*1/*1 genotype (p < 0.001), whereas the activity of ALDH2*2/*2 was too low to be precisely determined. The protein amounts of tissue ALDH2 in variant homozygotes and heterozygotes were similar but only 30 to 40% that of normal homozygotes (p < 0.01). Linear regression analyses show that ALDH2 activities were significantly correlated with the protein contents in normal homozygotes and heterozygotes, respectively (p < 0.005). The specific activity of ALDH2 per enzyme protein in ALDH2*1/*2 was 38% that of ALDH2*1/*1 (p < 0.001). CONCLUSIONS: These results are in good agreement with those predicted by the model studies, thus providing in vivo evidence for differential impairments of hepatic acetaldehyde oxidation with alcohol metabolism in individuals carrying ALDH2*1/*2 and ALDH2*2/*2 genotypes.

C-kit expression of melanocytic neoplasm and association with clinicopathological parameters and anatomic locations in Chinese people.

Distinct genetic aberrations between melanomas in different anatomical locations have been confirmed in recent years. However, the associations between immunohistochemical expression, tumor sites, and clinical parameters are not clear. We examined the correlation of protein expression and gene mutation of c-kit with clinicopathological parameters and lesion locations in patients with malignant melanoma (MM). We collected 170 melanocytic lesions, including 106 cutaneous MM from acral melanoma (AM) and nonacral melanoma (NAM) sites, 24 dysplastic nevi, and 40 common melanocytic nevi. Tissue microarray was constructed, and immunohistochemical expression for c-kit was assessed with correlation with clinical parameters. Mutation in exons 11, 13, 17, and 18 of KIT gene in genomic DNA by polymerase chain reaction sequencing was also analyzed. Immunostaining scores for c-kit were found to be statistically higher in Dysplastic Nevi than in common melanocytic nevi and MM. In addition, cytoplasmic c-kit staining was significantly correlated with poor survival in patients with AM but not in those with NAM. Twenty-nine cases of MM (including 9 NAM and 20 AM) are analyzed for mutation in exons 11, 13, 17, and 18 of KIT gene in genomic DNA by polymerase chain reaction sequencing, and no genetic mutation is found. Our findings confirm that KIT mutations, in contrast to previous white cohorts, are not common in both AM and NAM of the Chinese and do not necessarily correlate with c-kit expression. The significantly different association between the expression of c-kit immunoreactivities and the mortality risks of melanomas on acral versus nonacral sites might change site-specific targeted therapeutic concepts in melanoma in the future.

Risk of skin cancer in kidney, liver and heart recipients: A nationwide population-based study in Taiwan.

Background Previous population-based studies in western countries had revealed increased skin cancer risk among transplant recipients compared to the general population. However, population-based studies in Asia on skin cancer among recipients of different transplanted organs were lacking in the literature. Aims This study aims to estimate skin cancer risk among recipients in Taiwan, examine the association between each specific type of skin cancer and each type of transplanted organ, and compare skin cancer risk between different immunosuppressive regimens. Methods This population-based retrospective cohort study identified 7550 patients with heart, lung, kidney or liver transplantation and 30,200 controls matched for gender, age and comorbidity index from the National Health Insurance Research Database in Taiwan between 2000 and 2015. Using multivariable Cox proportional hazard models, we estimated the hazard ratios and 95% confidence intervals for the correlation of skin cancer with organ transplantation as well as immunosuppressive regimen. Results Organ transplant recipients in Taiwan had an increased risk of skin cancer with adjusted hazard ratios of 4.327 (95% confidence intervals 2.740-6.837, P < 0.001), with the greatest risk, observed among heart recipients (adjusted hazard ratios 6.348, 95% confidence intervals 3.080-13.088, P < 0.001). The risk of non-melanoma skin cancer and melanoma was 4.473 (95% confidence intervals 2.568-7.783, P < 0.001) and 3.324 (95% confidence intervals 1.300-8.172, P < 0.001), respectively. When comparing immunosuppressants, those with calcineurin inhibitors carried the highest risk of skin cancer (adjusted hazard ratios 4.789, 95% confidence intervals 3.033-7.569, P < 0.001), followed by those with antimetabolites (adjusted hazard ratios 4.771, 95% confidence intervals 3.025-7.541, P < 0.001). Limitations We could not evaluate confounding behavioural risk factors of skin cancers that were not documented in the database, nor could we recognize patients' compliance with immunosuppressants. Conclusion Organ recipients have a greater risk of skin cancer. Clinicians should inform recipients of the importance of photoprotection and regular dermatologic follow-up.

Hormone replacement therapy did not increase risk of melanoma in Chinese female with menopausal and postmenopausal disorders: A population-based retrospective cohort study in Taiwan.

Hormone replacement therapy (HRT) is widely used to relieve symptoms of menopause with proven efficacy. However, there has been significant controversy surrounding the use of HRT because of its potential link with an increased risk of cancer, particularly female reproductive organ cancers. That HRT increases the risk of melanoma is also disputed, and several cohort studies have produced variable results. To delineate the association between HRT and melanoma in Taiwan, we conducted a population-based retrospective cohort study on 14 291 patients who had received HRT and 57 164 population controls in Taiwan between 2000 and 2013. Multivariate odds ratios (ORs) were calculated utilizing conditional logistic regression. Overall, the use of HRT was not significantly correlated with a higher risk of developing melanoma in Taiwan (95% confidence interval 0.386-1.099; p = 0.341). The hazard ratio analysis of melanoma and different HRTs showed there was no significant association between melanoma and the use of oral or external estrogens alone, including conjugated estrogens, estradiol, and estriol. Estrogen plus progesterone combined therapy was associated with a lower risk of melanoma. Only one case of melanoma was observed among the 2880 patients in this subgroup.

Expression pattern, ethanol-metabolizing activities, and cellular localization of alcohol and aldehyde dehydrogenases in human small intestine.

BACKGROUND: Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) are principal enzymes responsible for metabolism of ethanol (EtOH). Functional polymorphisms of ADH1B, ADH1C, and ALDH2 genes occur among racial populations. This study aimed to systematically determine the functional expressions and cellular localization of ADH and ALDH family members in human small bowel. METHODS: One hundred and seventeen surgical specimens of duodenal mucosae, 34 jejunal mucosal specimens, and 14 paired specimens of stomach, duodenum, and jejunum from same individuals were investigated. The isozyme/allozyme expression patterns of ADH and ALDH were identified by isoelectric focusing, and the ADH/ALDH activities were assayed spectrophotometrically. The protein contents of ADH/ALDH isozymes were determined by immunoblotting using the corresponding purified class-specific antibodies, and the cellular localizations were detected by immunohistochemistry and histochemistry. RESULTS: The activities of ADH1C*1/*1 allelotype were significantly higher than those of the ADH1C*1/*2 allelotype in duodenum (p < 0.001) and in jejunum (p < 0.05); and the activity of ADH2-expressing phenotype was significantly higher than that of the ADH2-missing phenotype in duodenum (p < 0.05). The activities of ALDH2-inactive phenotype were not significantly different from those of the ALDH2-active phenotype in duodenum and jejunum. Stomach exhibited significantly lower ADH activity (p < 0.05), and duodenum displayed significantly lower ALDH activity (p < 0.001) comparing the paired gastric, duodenal, and jejunal mucosae of same individuals. Gender and age did not significantly influence the ADH and ALDH activities in duodenum. The isozyme protein contents in duodenum and jejunum were in the following decreasing order: ALDH1A1, ADH1/ALDH2, ADH3, ADH2, and ALDH3A1. Villous epithelial cells, cryptic Paneth cells, and Brunner's gland ductal cells revealed a greater immunostaining intensity with ADH1, ALDH1A1, and ALDH2. CONCLUSIONS: ADH and ALDH isozymes are differentially expressed in the various cell types of duodenum and jejunum. The results suggest that proximal small intestine can substantively contribute to first-pass metabolism of EtOH under certain conditions and that cytotoxic acetaldehyde and EtOH perturbation of retinol metabolism might play an etiological role in the pathogenesis of small bowel.

Investigating the Immunomodulatory Potential of Dental Pulp Stem Cell Cultured on Decellularized Bladder Hydrogel towards Macrophage Response In Vitro.

Mesenchymal stem cells (MSCs) possess immunomodulatory properties and capacity for endogenous regeneration. Therefore, MSC therapy is a promising treatment strategy for COVID-19. However, the cells cannot stay in the lung long enough to exert their function. The extracellular matrix from porcine bladders (B-ECM) has been shown not only to regulate cellular activities but also to possess immunoregulatory characteristics. Therefore, it can be hypothesized that B-ECM hydrogel could be an excellent scaffold for MSCs to grow and could anchor MSCs long enough in the lung so that they can exhibit their immunomodulatory functions. In this study, ECM degradation products and a co-culture system of MSCs and macrophages were developed to study the immunomodulatory properties of ECM and MSCs under septic conditions. The results showed that B-ECM degradation products could decrease pro-inflammatory and increase anti-inflammatory cytokines from macrophages. In an in vivo mimicking co-culture system, MSCs cultured on B-ECM hydrogel exhibited immunomodulatory properties at both gene and protein levels. Both B-ECM degradation products and MSC conditioned medium supported the wound healing of alveolar epithelial cells. The results from the study could offer a basis for investigation of immunomodulation by ECM and MSCs before conducting in vivo experiments, which could later be applied in regenerative medicine.

Real-Time Monitoring the Cytotoxic Effect of Andrographolide on Human Oral Epidermoid Carcinoma Cells.

Andrographolide is an active diterpenoid compound extracted from Andrographis paniculata. It exhibits antiinflammatory and anticancer effects. Previous studies show that it is non-toxic to experimental animals. The leading causes of cancer are chronic inflammation and high blood glucose. This study determines the cytotoxic effect of andrographolide on cellular morphology, viability, and migration for human oral epidermoid carcinoma cell Meng-1 (OEC-M1). We use electric cell-substrate impedance sensing (ECIS) to measure the subsequent overall impedance changes of the cell monolayer in response to different concentrations of andrographolide for 24 h (10-100 µM). The results for exposure of OEC-M1 cells to andrographolide (10-100 µM) for 24 h show a concentration-dependent decrease in the overall measured resistance at 4 kHz. AlamarBlue cell viability assay and annexin V also show the apoptotic effect of andrographolide on OEC-M1 cells. A reduction in wound-healing recovery rate is observed for cells treated with 30 µM andrographolide. This study demonstrates that ECIS can be used for the in vitro screening of anticancer drugs. ECIS detects the cytotoxic effect of drugs earlier than traditional biochemical assays, and it is more sensitive and shows more detail.

Clinician-created educational video for shared decision-making in the outpatient management of acne.

Shared decision-making (SDM) provides patient-centered care. However, the limited consultation time was the main factor hindering the application. Patient education is crucial in the process of SDM. The use of visual aids as health education materials is an effective way to improve patients' health literacy and medication adherence. This study aimed to determine the effectiveness of the clinician-created educational video of acne, accessed by patients during the waiting time, including knowledge level and satisfaction. This study was conducted in dermatology outpatient clinics and collected patient responses through electronic devices. During the waiting time, patients with acne would read educational pamphlets and complete the test first. Then, a clinician-created 8-minute educational video, as a patient decision aid (PDA), was accessed by patients using their own mobile smart devices, followed by a test and questionnaire about the satisfaction of the pamphlet and video. We enrolled 50 patients with acne, including 33 males and 17 females. The mean age is 25.55 ± 6.27 years old, ranging from 15 to 47 years old. About the patients' knowledge, the test score improved significantly after watching the video (P < .001). The same findings were observed in the subgroup analysis of gender and different age groups. A higher proportion of patients preferred the educational video over the pamphlet in both genders and different age groups. All patients agreed with the video helped them to understand the educational information and impressed them more than reading pamphlets. The application of clinician-created educational videos in patient education seems to be an efficient solution to implement SDM in the daily clinical work. Besides, we could remind patients to watch the video anytime when they were not sure about the treatment choices, side effects, or the precautions of medications.

Mechanisms of ultrasound-microbubble cavitation for inducing the permeability of human skin.

We have previously reported that ultrasound (US)-mediated microbubble (MB) cavitation (US-MB) changed the permeability of the skin and significantly enhanced transdermal drug delivery (TDD) without changing the structure of the skin. In this study we found that US-MB enhanced TDD via disruption of epidermal cell-cell junctions and increased matriptase activity. Matriptase is a membrane-bound serine protease regulated by its inhibitor hepatocyte growth factor activator inhibitor-1 (HAI-1), and it is expressed in most epithelial tissues under physiologic conditions. Matriptase is expressed in mice after chronic exposure to UV radiation. This study found that US-MB can be used to monitor active matriptase, which rapidly formed the canonical 120-kDa matriptase-HAI-1 complex. These processes were observed in HaCaT human keratinocytes when matriptase activation was induced by US-MB. The results of immunoblot analysis indicated that the matriptase-HAI-1 complex can be detected from 10 min to 3 h after US-MB. Immunohistochemistry (IHC) of human skin revealed that US-MB rapidly increased the activated matriptase, which was observed in the basal layer, with this elevation lasting 3 h. After 3 h, the activated matriptase extended from the basal layer to the granular layer, and then gradually decayed from 6 to 12 h. Moreover, prostasin expression was observed in the epidermal granular layer to the spinous layer, and became more obvious in the granular layer after 3 h. Prostasin was also detected in the cytoplasm or on the cell membrane after 6 h. These results suggest that matriptase plays an important role in recovering from US-MB-induced epidermal cell-cell junction disruption within 6 h. US-MB is therefore a potentially effective method for noninvasive TDD in humans.

Stevens-Johnson syndrome and toxic epidermal necrolysis associated with increased risk of developing psychiatric disorders: A retrospective population-based cohort study in Taiwan.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening adverse reactions to drugs and psychological sequelae are also observed to follow the trauma of widespread epidermal necrolysis. To delineate the association between SJS and TEN, and psychiatric disorders, we conducted a retrospective population-based cohort study by including 212 patients diagnosed with first-time SJS or TEN in Taiwan between 2000 and 2013 and 669 population controls. Adjusted hazard ratios were calculated after adjusting for sex, age, comorbidity in the form of Charlson comorbidity index, and facility level of care. Overall, SJS or TEN was associated with an increased risk of developing psychiatric disorders including schizophrenia, major depressive disorder, mania, anxiety, and bipolar with an adjusted hazard ratio of 1.392 (95% CI, 1.192-1.625; p < 0.001). Particularly, the adjusted hazard ratios of psychiatric disorders were 1.290 (95% CI, 1.105-1.506; p < 0.001) for SJS and 1.855 (95% CI, 1.587-2.167; p < 0.001) for TEN.

Minoxidil-Coated Lysozyme-Shelled Microbubbes Combined With Ultrasound for the Enhancement of Hair Follicle Growth: Efficacy In Vitro and In Vivo.

Lysozyme (Lyz) is an antimicrobial peptide, a safe adjunct, and it has been indicated that Lyz can promote vibrissae follicle growth by enhancing the hair-inductive capacity of dermal papilla cells in mice. The present study produced a new type of minoxidil (Mx)-coated antifungal Lyz-shelled microbubble (LyzMB) for inhibiting bacteria and allergies on the oily scalp. The potential of Mx-coated LyzMBs (Mx-LyzMBs) combined with ultrasound (US) and the role of LyzMB fragments in enhancing hair follicle growth were investigated. Mx grafted with LyzMBs were synthesized and the loading efficiency of Mx on cationic LyzMBs was 20.3%. The biological activity of Lyz in skin was determined using an activity assay kit and immunohistochemistry expression, and the activities in the US+Mx-LyzMBs group were 65.8 and 118.5 µU/mL at 6 and 18 h, respectively. In hair follicle cell culture experiments, the lengths of hair follicle cells were significantly enhanced in the US+Mx-LyzMBs group (108.2 ± 11.6 µm) compared to in the US+LyzMBs+Mx group (44.3 ± 9.8 µm) and the group with Mx alone (79.6 ± 12.0 µm) on day 2 (p < 0.001). During 21 days of treatment in animal experiments, the growth rates at days 10 and 14 in the US+Mx-LyzMBs group increased by 19.4 and 65.7%, respectively, and there were significant differences (p < 0.05) between the US+Mx-LyzMBs group and the other four groups. These findings indicate that 1-MHz US (applied at 3 W/cm2, acoustic pressure = 0.266 MPa) for 1 min combined with Mx-LyzMBs can significantly increase more penetration of Mx and LyzMB fragments into skin and enhance hair growth than Mx alone.

Fascin, cortactin and survivin expression of melanocytic neoplasms and association with clinicopathological parameters and anatomic locations in Chinese people.

Distinct genetic aberrations between melanomas in different anatomical locations have been confirmed in recent years. However, the associations between immunohistochemical expression, tumor sites, and clinical parameters are not clear. We examined the correlation of protein expression of fascin, cortactin and survivin with clinicopathological parameters and lesion locations in patients with cutaneous melanoma. We collected 170 melanocytic lesions, including 106 cutaneous malignant melanoma (MM) from acral (AM) and non-acral (NAM) sites, 24 dysplastic nevi (DN), and 40 common melanocytic nevi (CMN). Tissue micro arrays were constructed and immunohistochemical expression for cortactin, fascin, and survivin was assessed with correlation with clinical parameters. Cytoplasmic immunostaining for fascin was found to be significantly higher in CMN than DN, and survivin staining was significantly higher in DN than MM. Positive nuclear immunoreactivity for survivin was seen in a large subset of melanomas but much less frequently in CMN and DN. In addition, nuclear survivin immunoreactivity was significantly more common in NAM than in AM. Nuclear survivin staining in patients with NAM was significantly correlated with poor survival. The significantly different expression of immunoreactivities (nuclear survivin) between AM and NAM and the different mortality risks of melanomas on acral versus non-acral sites might change site-specific therapeutic concepts in melanoma.

Application of ultrasound-mediated adapalene-coated lysozyme-shelled microbubbles in UVA-induced skin photoaging.

Photoaging, the premature aging of skin induced by ultraviolet rays, is characterized by wrinkling, roughness, laxity, and pigmentary changes. Various natural and synthetic retinoids have been explored for the treatment of aging. Among retinoids, adapalene (Ada, 0.3%) is one of the most potent and widely used drugs to treat photoaging. However, it causes irritant reactions that limit its acceptance by patients. Several studies have shown the applicability of Lysozyme (Lys)-shelled microbubbles (MBs) for drug delivery through sonophoresis, and recently we have shown its efficiency to treat inflammatory skin disease. Here, we report the construction of novel Ada-LysMBs based on opposite electric charges for combined effects to treat photoaging. The Ada-LysMBs were self-assembled and had a mean diameter of 2857 nm. The maximum loading efficiency of Ada onto LysMBs was 13.99 ± 0.59%. An acoustic power density of 3 W/cm2 for 1 min revealing maximum penetration depth of LysMBs was optimized for further in vitro and in vivo studies of Ada-LysMBs. It was observed that in vitro Ada release from Ada-LysMBs at 6 h after ultrasound (US) treatment was more rapid at pH 7.4 (82%) than at pH 5.5 (73%). Franz diffusion experiments on isolated porcine skin indicated that US approximately doubled Ada delivery by Ada-LysMBs and Ada + LysMBs at 12 h and six-fold Lys permeation by LysMBs at 6 h, compared to these treatments alone. A 5-week in vivo study in mice identified significant wrinkle reduction in animals treated with US plus Ada-LysMBs. Our findings indicate that US may be used with Ada-LysMBs in the water phase to treat photoaging by normalizing hyperkeratinization and promoting collagen synthesis.

Increased risk of bullous pemphigoid in dipeptidyl peptidase 4 inhibitors: A nationwide, population-based, cohort study in Taiwan.

Recent studies revealed the risk of bullous pemphigoid (BP) in patients with diabetes mellitus (DM) taking dipeptidyl peptidase 4 (DPP-4) inhibitors. To clarify the relationship between taking DPP-4 inhibitors and the risk of BP among patients with DM, we conducted a cohort study by using the National Health Insurance Research Database of Taiwan from 1 January 2009 to 31 December 2015. We identified 6340 patients with DM taking DPP-4 inhibitors and 25 360 DM patients who had not taken DPP-4 inhibitors during the 7-year follow-up period. Compared with the non-DPP-4 inhibitor group, patients taking DDP-4 inhibitors had a higher risk of BP (adjusted hazard ratio [aHR], 2.382; 95% confidence interval (CI), 1.163-4.883; P = 0.017]. Among the DPP-4 inhibitors available in Taiwan, vildagliptin showed the highest risk of BP (aHR, 2.849; 95% CI, 1.893-4.215; P < 0.001), followed by saxagliptin (aHR, 2.657; 95% CI, 1.770-3.934; P < 0.001). Subgroup analysis revealed that the higher risk of BP was observed in patients older than 65 years (aHR, 2.403; 95% CI, 1.590-3.627; P < 0.001). This study revealed that treatment with DPP-4 inhibitors, especially vildagliptin, was significantly associated with an increased risk of BP among DM patients.