Amauroderma rugosum Extract Suppresses Inflammatory Responses in Tumor Necrosis Factor Alpha/Interferon Gamma-Induced HaCaT Keratinocytes.

Keratinocytes form the physical barrier of the skin and play an important role in the inflammatory process. Amauroderma rugosum is an edible mushroom; however, its pharmacological properties have seldom been studied. Although the anti-inflammatory effect of the organic solvent extract of Amauroderma rugosum has been previously reported, it is not known whether the aqueous extract has a similar effect. In addition, the effect of Amauorderma rugosum extract on skin has never been explored. Therefore, the objectives of the present study were to evaluate the anti-inflammatory effects of the aqueous extract of Amauroderma rugosum on HaCaT keratinocytes, to explore its mechanisms of action, and to study the possible active ingredients involved. The results showed that the aqueous extract of Amauroderm rugosum at a concentration of 1.5 mg/mL was non-toxic to HaCaT cells and inhibited the release of cytokine interleukin-1ß, and chemokines interleukin-8 and monocyte chemoattractant protein-1 in tumor necrosis factor (TNF)-α- and interferon (IFN)-γ-stimulated HaCaT cells. Amauroderma rugosum extract reduced the intracellular levels of reactive oxygen species. In addition, Amauroderma rugosum extract reduced the total protein expression of nuclear factor-kappa B (NF-κB) and B-cells inhibitor alpha in HaCaT keratinocytes and inhibited the phosphorylation of mitogen-activated protein kinase kinase (MEK) 1/2, extracellular signal-regulated kinase (ERK) 1/2, protein kinase B (Akt), and mammalian target of rapamycin (mTOR) in TNF-α- and INF-γ-stimulated HaCaT keratinocytes. Chemical analysis revealed that the aqueous extract of Amauroderma rugosum contains polysaccharides, triterpenes, and phenolic compounds. Anti-inflammatory compounds, such as gallic acid, guanosine, and uridine, were also present. The anti-inflammatory effect of Amauroderma rugosum could be mimicked by a combination of gallic acid, guanosine, and uridine. In conclusion, our study suggests that the aqueous extract of Amauroderma rugosum exerts anti-inflammatory effects on keratinocytes through its antioxidant and inhibitory effects on MEK/ERK-, Akt/mTOR-, and NF-κB-dependent signaling pathways.

Morphoea following COVID-19 vaccination.

We present a case of generalized morphoea developing after recent COVID-19 mRNA vaccination and suggest the plausible pathomechanisms.

Patients' Experiences of Telemedicine for Their Skin Problems: Qualitative Study.

BACKGROUND: Teledermatology is a cost-effective treatment modality for the management of skin disorders. Most evaluations use quantitative data, and far less is understood about the patients' experience. OBJECTIVE: This qualitative study aimed to explore patients' perceptions of a teledermatology service linking public primary care clinics to the national specialist dermatology clinic in Singapore. A better understanding of patients' experiences can help refine and develop the care provided. METHODS: Semistructured in-depth interviews were conducted with patients who had been referred to the teledermatology service. The interviews were digitally recorded and transcribed before undergoing thematic content analysis. RESULTS: A total of 21 patients aged between 22 and 72 years were recruited. The following 3 themes were identified from the data of patients' experiences: positive perceptions of teledermatology, concerns about teledermatology, and ideas for improving the teledermatology service. The patients found the teledermatology service convenient, saving them time and expense and liberating them from the stresses incurred when making an in-person visit to a specialist facility. They valued the confidence and reassurance they gained from having a dermatologist involved in deciding their management. The patients' concern included data security and the quality of the images shared. Nonetheless, they were keen to see the service expanded beyond the polyclinics. Their experiences and perceptions will inform future service refinement and development. CONCLUSIONS: This narrative exploration of users' experiences of teledermatology produced rich data enabling a better understanding of the patients' journey, the way they understand and interpret their experiences, and ideas for service refinement. Telemedicine reduces traveling and enables safe distancing, factors that are much needed during pandemics.

Intranasal octenidine for methicillin-resistant Staphylococcus aureus (MRSA) carriers and universal octenidine bathing reduced MRSA acquisition in an acute-care general ward.

In this quasi-experimental before-and-after study in a methicillin-resistant staphylococcus aureus (MRSA) high-prevalence acute-care dermatology ward from August 2016 to November 2018, patients admitted during intervention period who received additional topical intranasal octenidine were 63% less likely to acquire MRSA than those receiving universal daily octenidine bathing alone during baseline period (aOR, 0.37; 95% CI, 0.14-0.98).

Teledermatology in Primary Care in Singapore: Experiences of Family Doctors and Specialists.

Most teledermatology studies focus on patients' satisfaction; fewer focus on the experiences of healthcare professionals. This qualitative study explored healthcare professionals' perceptions of teledermatology used for linking public primary care clinics with the specialist dermatology centre in Singapore. Semi-structured in-depth interviews were conducted with 25 family physicians and dermatologists. Six themes were identified: satisfaction with the service; perceived patient benefits; rationale for introducing teledermatology; educational impact; challenges of virtual consultations; and desirable service refinements for the future. Family physicians and dermatologists were positive about the service, but highlighted a need to streamline referral processes and improve the quality of transmitted images. Reduced need for referral to the specialist centre could be achieved by expanding the polyclinic's pharmacopoeia and treatment modalities. This study highlights the benefits of telemedicine for patient, professionals, and healthcare organizations, and these are reassuring given the widespread and rapid introduction of telemedicine through necessity during the COVID-19 pandemic.

ß-Lactam allergy testing and delabeling-Experiences and lessons from Singapore.

BACKGROUND: ß-Lactam allergy is over-reported and this leads to greater healthcare costs. Allergy testing has inherent risks, yet patients who test negative may continue avoiding ß-lactams. OBJECTIVE: To evaluate the safety and diagnostic value of ß-lactams allergy testing locally and usage of antibiotics following negative testing. METHODS: We performed a retrospective medical record review and follow-up survey of patients who underwent ß-lactam testing between 2010 and 2016 at the National Skin Centre, Singapore. RESULTS: We reviewed the records of 166 patients, with a total of 173 ß-lactam allergy labels. Eighty (46.2%) labels were to penicillin, 75 (43.1%) to amoxicillin/amoxicillin-clavulanic acid, 11 (6.4%) to cephalexin, and 5 (2.9%) to others. Skin tests were performed in 142 patients and drug provocation tests (DPTs) in 141 patients. Eleven (6.6%) patients defaulted DPTs after skin testing. Out of 166 patients, 22 (13.3%) patients were proven allergic by either skin tests (16) or DPTs (6). Patients who tested positive had nonsevere reactions. Out of 155 patients who were conclusively evaluated, 133 (85.8%) were not allergic. Of these patients, 30 (22.6%) used the tested ß-lactam subsequently, with one reporting a mild reaction. Fifty-one (38.3%) patients were uncontactable or uncertain if they consumed a ß-lactam since testing negative. Fifty-two (39.1%) patients had no re-exposure (35 had no indication, 17 were fearful of reactions). CONCLUSION: Drug allergy testing was safe and removed inappropriate labels. CLINICAL IMPLICATION: Allergy testing is efficacious, but fears of subsequent rechallenge should be addressed to maximize the effectiveness of allergy delabeling.

Penile Ulcer due to Leukemia Cutis-A Rare Diagnosis Not to Be Missed.

We present a rare case of leukemia cutis presenting with an ulcer on the ventral penis. A 60-year-old Chinese man was referred for a penile ulcer of 10 days. He was diagnosed with acute myelomonocytic leukemia 6 months earlier and had received 2 cycles of venetoclax with azacitidine. He developed a spontaneous penile blister. It ulcerated after the patient pricked it with a needle. This enlarged after traditional medicated ointment was applied. He denied pain, itch, urethral discharge, systemic symptoms, or rashes elsewhere.

A simple and inexpensive physical lysis method for DNA and RNA extraction from freshwater microalgae.

In this work, a simple and inexpensive physical lysis method using a cordless drill fitted with a plastic pellet pestle and 150 mg of sterile sea sand was established for the extraction of DNA from six strains of freshwater microalgae. This lysis method was also tested for RNA extraction from two microalgal strains. Lysis duration between 15 and 120 s using the cetyltrimethyl ammonium bromide (CTAB) buffer significantly increased the yield of DNA from four microalgalstrains (Monoraphidium griffithii NS16, Scenedesmus sp. NS6, Scenedesmus sp. DPBC1 and Acutodesmus sp. DPBB10) compared to control. It was also found that grinding was not required to obtain DNA from two strains of microalgae (Choricystis sp. NPA14 and Chlamydomonas sp. BM3). The average DNA yield obtained using this lysis method was between 62.5 and 78.9 ng/mg for M. griffithii NS16, 42.2-247.0 ng/mg for Scenedesmus sp. NS6, 70.2-110.9 ng/mg for Scenedesmus sp. DPBC1 and 142.8-164.8 ng/mg for Acutodesmus sp. DPBB10. DNA obtained using this method was sufficiently pure for PCR amplification. Extraction of total RNA from M. griffithii NS16 and Mychonastes sp. NPD7 using this lysis method yielded high-quality RNA suitable for RT-PCR. This lysis method is simple, cheap and would enable rapid nucleic acid extraction from freshwater microalgae without requiring costly materials and equipment such as liquid nitrogen or beadbeaters, and would facilitate molecular studies on microalgae in general.

Metformin Inhibits Cellular Proliferation and Bioenergetics in Colorectal Cancer Patient-Derived Xenografts.

There is increasing preclinical evidence suggesting that metformin, an antidiabetic drug, has anticancer properties against various malignancies, including colorectal cancer. However, the majority of evidence, which was derived from cancer cell lines and xenografts, was likely to overestimate the benefit of metformin because these models are inadequate and require supraphysiologic levels of metformin. Here, we generated patient-derived xenograft (PDX) lines from 2 colorectal cancer patients to assess the properties of metformin and 5-fluorouracil (5-FU), the first-line drug treatment for colorectal cancer. Metformin (150 mg/kg) as a single agent inhibits the growth of both PDX tumors by at least 50% (P < 0.05) when administered orally for 24 days. In one of the PDX models, metformin given concurrently with 5-FU (25 mg/kg) leads to an 85% (P = 0.054) growth inhibition. Ex vivo culture of organoids generated from PDX demonstrates that metformin inhibits growth by executing metabolic changes to decrease oxygen consumption and activating AMPK-mediated pathways. In addition, we also performed genetic characterizations of serial PDX samples with corresponding parental tissues from patients using next-generation sequencing (NGS). Our pilot NGS study demonstrates that PDX represents a useful platform for analysis in cancer research because it demonstrates high fidelity with parental tumor. Furthermore, NGS analysis of PDX may be useful to determine genetic identifiers of drug response. This is the first preclinical study using PDX and PDX-derived organoids to investigate the efficacy of metformin in colorectal cancer. Mol Cancer Ther; 16(9); 2035-44. ©2017 AACR.

Actinic Prurigo in Singaporean Chinese: A Positive Association with HLA-DRB1*03:01.

Studies have reported the association of human leukocyte antigen (HLA) genes with susceptibility to develop actinic prurigo (AP) in Caucasians, but there were no studies in Asian populations, including the Chinese. Our study was performed to determine if AP is associated with susceptibility or protective HLA alleles or haplotypes in Singaporean Chinese. All Chinese patients diagnosed with AP at National Skin Center, Singapore, from January 2002 to April 2015 were invited to participate in the study. Clinical data and phototesting results were collated, and HLA typing was performed. Among 14 patients included, 11 were male and the mean age was 49.6 (37.9-61.3) years. All patients did not have a family history of AP and none had mucosal involvement, as such these clinical features differed from Caucasian AP patients. The frequency of DRB1*03:01 in AP patients was significantly higher compared to healthy controls (43% vs 16%, P = 0.022, odds ratio (OR) 3.89). Concurrently, the frequency of HLA-B*58:01-DRB1*03:01 haplotype was also significantly increased (25% vs 7%, P = 0.004, OR 4.23). In conclusion, HLA-DRB1*03:01 was associated with AP in Singaporean Chinese patients. This novel allelic association may possibly be utilized as a biological marker to aid in the diagnosis of AP in Chinese patients.

Cutaneous adverse drug reactions in the elderly.

PURPOSE OF REVIEW: Population ageing is a worldwide phenomenon. The presence of multiple comorbidities, polypharmacy, age-related changes in pharmacokinetics and pharmacodynamics, as well as skin changes in the elderly contribute to a unique diagnostic and management problem. This article reviews the epidemiology of cutaneous adverse drug reactions in the elderly and elaborates on a few specific types of reactions which are more relevant to the elderly. RECENT FINDINGS: Chronic dermatoses, for example, eczema, have been reported to be associated with the use of long-term medications such as calcium channel blockers and hydrochlorothiazide. Elderly patients receiving treatment for cancers may develop chemotherapy-related cutaneous side effects, including those associated with newer 'targeted' molecular therapies. Elderly patients who develop severe cutaneous adverse drug reactions, such as Stevens-Johnson syndrome and toxic epidermal necrolysis, have worse prognosis in terms of mortality. SUMMARY: Persons of advanced age often have multiple comorbidities and are on multiple medications. This can result in higher probability of an elderly person developing drug eruptions. It is important for the clinician to be aware of the range of drug-related eruptions and their implications.

Expansion of the lateral ventricles and ependymal deficits underlie the hydrocephalus evident in mice lacking the transcription factor NFIX.

Nuclear factor one X (NFIX) has been shown to play a pivotal role during the development of many regions of the brain, including the neocortex, the hippocampus and the cerebellum. Mechanistically, NFIX has been shown to promote neural stem cell differentiation through the activation of astrocyte-specific genes and via the repression of genes central to progenitor cell self-renewal. Interestingly, mice lacking Nfix also exhibit other phenotypes with respect to development of the central nervous system, and whose underlying causes have yet to be determined. Here we examine one of the phenotypes displayed by Nfix(-/-) mice, namely hydrocephalus. Through the examination of embryonic and postnatal Nfix(-/-) mice we reveal that hydrocephalus is first seen at around postnatal day (P) 10 in mice lacking Nfix, and is fully penetrant by P20. Furthermore, we examined the subcommissural organ (SCO), the Sylvian aqueduct and the ependymal layer of the lateral ventricles, regions that when malformed and functionally perturbed have previously been implicated in the development of hydrocephalus. SOX3 is a factor known to regulate SCO development. Although we revealed that NFIX could repress Sox3-promoter-driven transcriptional activity in vitro, SOX3 expression within the SCO was normal within Nfix(-/-) mice, and Nfix mutant mice showed no abnormalities in the structure or function of the SCO. Moreover, these mutant mice exhibited no overt blockage of the Sylvian aqueduct. However, the ependymal layer of the lateral ventricles was frequently absent in Nfix(-/-) mice, suggesting that this phenotype may underlie the development of hydrocephalus within these knockout mice.

Lichen nitidus presenting with nail changes--case report and review of the literature.

Lichen nitidus of the nail is rare and can precede the onset of skin lesions. Delayed diagnosis is common. We present an unusual case of lichen nitidus-associated nail changes that preceded the onset of skin lesions in a 4-year-old Indian girl. We also conduct a review of six other cases of lichen nitidus with nail involvement from the English-language literature. Clues to the diagnosis of lichen nitidus include violaceous or pigmentary changes of the nail fold and subtle lichenoid papules on the affected digits. Lichen nitidus of the nails appears to be less severe than nail changes of lichen planus and is generally self-limiting. Understanding the natural history of lichen nitidus of the nails will help physicians better counsel patients and their families.

NFIX Regulates Proliferation and Migration Within the Murine SVZ Neurogenic Niche.

Transcription factors of the nuclear factor one (NFI) family play a pivotal role in the development of the nervous system. One member, NFIX, regulates the development of the neocortex, hippocampus, and cerebellum. Postnatal Nfix(-/-) mice also display abnormalities within the subventricular zone (SVZ) lining the lateral ventricles, a region of the brain comprising a neurogenic niche that provides ongoing neurogenesis throughout life. Specifically, Nfix(-/-) mice exhibit more PAX6-expressing progenitor cells within the SVZ. However, the mechanism underlying the development of this phenotype remains undefined. Here, we reveal that NFIX contributes to multiple facets of SVZ development. Postnatal Nfix(-/-) mice exhibit increased levels of proliferation within the SVZ, both in vivo and in vitro as assessed by a neurosphere assay. Furthermore, we show that the migration of SVZ-derived neuroblasts to the olfactory bulb is impaired, and that the olfactory bulbs of postnatal Nfix(-/-) mice are smaller. We also demonstrate that gliogenesis within the rostral migratory stream is delayed in the absence of Nfix, and reveal that Gdnf (glial-derived neurotrophic factor), a known attractant for SVZ-derived neuroblasts, is a target for transcriptional activation by NFIX. Collectively, these findings suggest that NFIX regulates both proliferation and migration during the development of the SVZ neurogenic niche.

Eccrine syringofibroadenomatosis of the reactive subtype occurring in chronic poorly-controlled psoriasis.

Eccrine syringofibroadenomatosis (ESFA) is a rare adnexal tumor with acrosyringeal differentiation. Clinically, it can be mistaken for granulomatous infections or malignancies such as squamous cell carcinoma. Despite the rarity of the condition, we recently encountered two cases of the reactive subtype, which occurred in patients with poorly controlled chronic psoriasis. Both patients presented with long-standing, thick verrucous lesions on the lower legs. The diagnosis was made after histological examination and exclusion of infectious and neoplastic disorders. As this is a reactive disorder, management is focused on treating the underlying condition. Unfortunately, psoriasis was difficult to manage in both our patients and they defaulted further treatment. It is important to recognize ESFA as it can be confused with infectious or malignant disorders.