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The breadth of therapeutic options for the management of dermatologic skin conditions continues to expand rapidly as exemplified by biologics and small molecule drug development. While dermatologists and health care providers are aware of the underlying mechanisms and indications for these therapeutics, there is a recognized practice gap due to an incomplete understanding of the safety of these medications in women of childbearing age during the prepartum, antepartum, and postpartum phases. Although a two-part continuing medical education review was published regarding the prescribing practices and safety profiles of these new therapeutics in women of childbearing age while pregnant or lactating in 2014, many new medications have been approved since then. Herein, we will update the safety of dermatologic therapies during pregnancy and Part II will review the safety of medications during lactation., Competing Interests: Conflicts of interest Dr Rothe is a stockholder in the following companies: Eli Lilly and Co, Merck and Co, GE Healthcare, Organon and Co, and Pfizer Inc. Drs McMullan, Yaghi, Truong, Murase, and Grant-Kels have no conflicts to declare., (Copyright © 2024 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Multiple recently approved medications have been added to our treatment armamentarium for various dermatologic conditions. Herein, we have reviewed the literature, consolidated available safety data, and offered recommendations based upon available evidence as a reference guide for clinicians treating patients for dermatologic conditions during lactation., Competing Interests: Conflicts of interest None disclosed., (Copyright © 2024 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Microdermabrasion is a cosmetic procedure that has gained popularity for skin rejuvenation by causing repetitive intraepidermal injury to stimulate the proliferation of fibroblasts and collagen production. Various clinical studies have demonstrated microdermabrasion's effectiveness in skin rejuvenation; however, most of these studies rely on clinical observation and scoring by observers rather than histologic or microscopic analysis. In our single-center prospective study, we used line-field confocal optical coherence tomography (LC-OCT), to non-invasively visualize the early effects of one microdermabrasion treatment on the facial epidermal and dermal structure., Aim: Using LC-OCT, this study aims to elucidate the microscopic and histological effects of microdermabrasion on epidermal and dermal structures, including epidermal thickness, as well as collagen and vascular patterns., Patients/methods: Eight volunteers (Fitzpatrick skin types II-V) underwent one treatment of microdermabrasion. LC-OCT and VISIA imaging were performed before and 10 min after microdermabrasion, and at 48-h follow-up. Subjective evaluations of skin texture and adverse reactions were assessed 1 week posttreatment via a telephone call., Results: Compared to LC-OCT images before treatment, images captured after one treatment of microdermabrasion showed a decrease in thickness and number of undulations in the stratum corneum. In the superficial dermis, enhancement in fibrillar collagen, as demonstrated by an increased prominence of crisscrossing hyper-refractile strands, was visualized. This was consistent with subjective and objective improvement in facial rhytids calculated by VISIA skin analysis., Conclusions: Treatment monitoring with LC-OCT demonstrated consistent histopathological changes with clinical visual improvement. Therefore, LC-OCT, has the potential to enable long-term histopathological monitoring of microdermabrasion and other cosmetic procedures without biopsy., (© 2024 The Authors. Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Background: Preclinical models recapitulating the metastatic phenotypes are essential for developing the next-generation therapies for metastatic prostate cancer (mPC). We aimed to establish a cohort of clinically relevant mPC models, particularly androgen receptor positive (AR + ) bone metastasis models, from LuCaP patient-derived xenografts (PDX) that reflect the heterogeneity and complexity of mPC., Methods: PDX tumors were dissociated into single cells, modified to express luciferase, and were inoculated into NSG mice via intracardiac injection. The progression of metastases was monitored by bioluminescent imaging. Histological phenotypes of metastases were characterized by immunohistochemistry and immunofluorescence staining. Castration responses were further investigated in two AR-positive models., Results: Our PDX-derived metastasis (PDM) model collection comprises three AR + adenocarcinomas (ARPC) and one AR - neuroendocrine carcinoma (NEPC). All ARPC models developed bone metastases with either an osteoblastic, osteolytic, or mixed phenotype, while the NEPC model mainly developed brain metastasis. Different mechanisms of castration resistance were observed in two AR + PDM models with distinct genotypes, such as combined loss of TP53 and RB1 in one model and expression of AR splice variant 7 (AR-V7) expression in another model. Intriguingly, the castration-resistant tumors displayed inter- and intra-tumor as well as organ-specific heterogeneity in lineage specification., Conclusion: Genetically diverse PDM models provide a clinically relevant system for biomarker identification and personalized medicine in metastatic castration-resistant prostate cancer., (© 2024 The Authors. The Prostate published by Wiley Periodicals LLC. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Pemphigus represents a spectrum of autoimmune-mediated blistering diseases associated with high morbidity, mortality and reduced quality of life (QoL). Despite an increase in pemphigus clinical trials, the varied instrument measurements of disease severity and QoL outcomes make comparisons between studies challenging. This study aimed to evaluate trends in the use of disease severity and QoL outcome measurements in pemphigus clinical trials. A review of pemphigus clinical trials was conducted using the PubMed, Embase, Cochrane Reviews and ClinicalTrials.gov databases up until September 2023. Only pemphigus randomized clinical trials that assessed at least one disease severity and/or QoL outcome were included. Overall, 53 clinical trials were eligible for this review. All clinical trials evaluated a disease severity outcome, with the Pemphigus Disease Area Index being the most used validated questionnaire (28.3% of trials) and more popular after 2015 (47.8% of trials since). The autoimmune bullous skin disorder intensity score (7.6%) and visual analogue measurements (7.6%) have fallen out of favour. Most studies now include lab parameters (56.5% of trials after 2015), with anti-desmoglein 1 and 3 antibody levels (30.2%), immunoglobulins (IgG and/or IgM and IgA) (11.3%), and anti-drug antibody levels (7.6%) being frequently evaluated. A small portion of trials evaluated QoL (26.5% of studies), with the autoimmune bullous quality of life being the most common (15.1%), however QoL utilization as an outcome measure has been increasing since 2015 (61.1% of trials since). Standardising the use of validated outcome measurements allows for better data interpretation, comparability and clinical application of results., Competing Interests: Dr. Rao is a speaker for Incyte and Amgen. The authors declare no conflicts of interest., (© 2024 The Author(s). Skin Health and Disease published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)

Introduction: In Viet Nam, key populations (KPs) face barriers accessing HIV services. Virtual platforms can be leveraged to increase access for KPs, including for HIV self-testing (HIVST). This study compares reach and effectiveness of a web-based HIVST intervention from pilot to scale-up in Viet Nam., Methods: A mixed-methods explanatory sequential design used cross-sectional and thematic analysis. The pilot launched in Can Tho in November 2020, followed by Hanoi and Nghe An in April 2021. Scale-up included Can Tho and Nghe An, with 21 novel provinces from April to December 2022. After risk assessment, participants registered on the website, receiving HIVST (OraQuick®) by courier, peer educator or self-pick-up. Test result reporting and completing satisfaction surveys were encouraged. Intervention reach was measured through numbers accessing the testing, disaggregated by demographics, and proportion of individuals reporting self-testing post-registration. Effectiveness was measured through numbers reporting self-test results, testing positive and linking to care, and testing negative and using HIVST to manage pre-exposure prophylaxis (PrEP) use. Thematic content analysis of free-text responses from the satisfaction survey synthesized quantitative outcomes., Results: In total, 17,589 participants registered on the HIVST website; 11,332 individuals ordered 13,334 tests. Participants were generally young, aged <25 years (4309/11,332, 38.0%), male (9418/11,332, 83.1%) and men who have sex with men (6437/11,332, 56.8%). Nearly half were first-time testers (5069/11,332, 44.9%). Scale-up participants were two times more likely to be assigned female at birth (scale-up; 1595/8436, 18.9% compared to pilot; 392/3727, 10.5%, p < 0.001). Fewer test results were reported in scale-up compared with pilot (pilot: 3129/4140, 75.6%, scale-up: 5811/9194, 63.2%, p < 0.001). 6.3% of all tests were reactive (pilot: 176/3129, 5.6% reactive compared to scale-up: 385/5811, 6.6% reactive, p = 0.063); of which most linked to care (509/522, 97.5%). One-fifth of participants with a negative test initiated or continued PrEP (pilot; 19.8%, scale-up; 18.5%, p = 0.124). Thematic analysis suggested that community delivery models increased programmatic reach. Live chat may also be a suitable proxy for staff support to increase result reporting., Conclusions: Web-based self-testing in Viet Nam reached people at elevated risk of HIV, facilitating uptake of anti-retroviral treatment and direct linkage to PrEP initiations. Further innovations such as the use of social-network testing services and incorporating features powered by artificial intelligence could increase the effectiveness and efficiency of the approach., (© 2024 World Health Organization; licensed by AIS. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of International AIDS Society.)

Sustainable cellulose-based hydrogels are used in medicine and environmental science. Hydrogels' porosity makes them excellent adsorbents and stable substrates for immobilizing photocatalysts to remove organic dyes. Despite their potential, the implementation of hydrogels for this purpose is still limited due to their high synthesis temperature and low cellulose content. To overcome these challenges, this study develops cellulose-based hydrogels, which have a high cellulose content and can be easily synthesized under ambient conditions. Containing a higher cellulose concentration than previous hydrogels, the synthesized hydrogels are more stable and can be reused numerous times in treatment operations. The hydrogel properties were investigated using Fourier transform infrared spectroscopy, X-ray diffraction and thermal analysis. Scanning electronic microscopy revealed that TiO 2 nanoparticles were homogeneously distributed throughout the hydrogel's matrices. In addition, transparent hydrogels allow light to pass through, making them suitable substrates to remove organic dye. The results showed that the hydrogel with TiO 2 was able to degrade nearly 90% of organic dye within 180 min. Furthermore, the hydrogel with the embedded catalyst exhibits the potential for reusability with a regeneration efficiency of 80.01% after five runs. These findings suggest that this novel hydrogel is a promising candidate for water pollution remediation., (© 2024. The Author(s).)

Objective: The objective of this study was to review the safety and efficacy of deucravacitinib, a tyrosine kinase 2 (TYK2) inhibitor for moderate to severe plaque psoriasis., Data Sources: Literature was reviewed from MEDLINE and Clinicaltrials.gov up to December 2022 using the terms "deucravacitinib" and "BMS-986165.", Study Selection: Relevant articles in English relating to the pharmacodynamics, pharmacokinetics, efficacy, and safety of deucravacitinib were included. A total of 6 trial results were included., Study Selection and Data Extraction: Deucravacitinib showed clinical efficacy across all the phase II and III clinical trials. Excluding the long-term extension study, there were 2248 subjects across all studies, with 63.2% of patients receiving deucravacitinib 6 mg daily. Of these subjects, the average proportion achieving a PASI 75 (a reduction of greater than 75% in the Psoriasis Area and Severity Index) at week 16 was 65.1%. Patients receiving deucravacitinib 6 mg once daily had a higher rate of achieving both PASI 75 response and a Static Physician's Global Assessment (sPGA) score of 0 or 1, compared with oral apremilast 30 mg twice daily. The safety profile of deucravacitinib includes mild adverse events (AEs), most commonly nasopharyngitis, with serious AEs reported ranging from 1.35% to 9.5%., Relevance to Patient Care and Clinical Practice in Comparison With Existing Medications: While many available therapies for moderate to severe plaque psoriasis rely on an injectable dosage form or extensive monitoring, deucravacitinib can potentially reduce patient medication-related burden. This review summarizes the efficacy and safety of oral deucravacitinib for the treatment of severe plaque psoriasis., Conclusion: Deucravacitinib shows a consistent efficacy and safety profile as the first oral TYK2 inhibitor approved for adult patients with moderate to severe plaque psoriasis who are eligible for systemic therapy or phototherapy treatment., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Artificial intelligence (AI) uses algorithms and large language models in computers to simulate human-like problem-solving and decision-making. AI programs have recently acquired widespread popularity in the field of dermatology through the application of online tools in the assessment, diagnosis, and treatment of skin conditions. A literature review was conducted using PubMed and Google Scholar analyzing recent literature (from the last 10 years through October 2023) to evaluate current AI programs in use for dermatologic purposes, identifying challenges in this technology when applied to skin of color (SOC), and proposing future steps to enhance the role of AI in dermatologic practice. Challenges surrounding AI and its application to SOC stem from the underrepresentation of SOC in datasets and issues with image quality and standardization. With these existing issues, current AI programs inevitably do worse at identifying lesions in SOC. Additionally, only 30% of the programs identified in this review had data reported on their use in dermatology, specifically in SOC. Significant development of these applications is required for the accurate depiction of darker skin tone images in datasets. More research is warranted in the future to better understand the efficacy of AI in aiding diagnosis and treatment options for SOC patients., (© 2024 The Authors. International Journal of Dermatology published by Wiley Periodicals LLC on behalf of the International Society of Dermatology.)

Background: Hydradermabrasion, also known as "HydraFacial," is an exfoliative cosmetic procedure for skin rejuvenation that has gained popularity. Despite its increasing popularity, clinical studies validating its efficacy with non-invasive assessment of histological changes to the skin, are scarce. In this study, we used Line-Field Confocal Optical Coherence Tomography (LC-OCT), an optical imaging device, to non-invasively visualize microscopic changes to skin anatomy after hydradermabrasion treatment., Materials/methods: Eight volunteers (Fitzpatrick skin types II-V) were recruited for this study. Images, using LC-OCT (DeepLive, DAMAE medical) were obtained before and after hydradermabrasion and at 2 weeks post-treatment. A commercially available hydradermabrasion device was utilized to perform the dermabrasion., Results: In the epidermis, initially, a decrease in the average thickness of the stratum corneum, from 9.42 to 6.67 µm was visualized in LC-OCT images after hydradermabrasion. However, at 2 weeks of follow-up, the average stratum corneum thickness was 9.75 µm, resulting in an overall increase in the average thickness after treatment. Improved homogenization of the stratum corneum and decreased number of undulations in the epidermis post-treatment were also visualized. In all the subjects, the superficial dermis appeared stretched, which returned to baseline by the 2-week follow-up. At the 2-week follow-up, there were no visible differences in the quality and quantity of collagen fibers in the dermis., Conclusion: In our study, LC-OCT images of the epidermis and dermis demonstrated microscopic features of skin rejuvenation when treated with hydradermabrasion. Thus, not only highlighting the efficacy of hydradermabrasion but also the potential of LC-OCT to serve as a tool for visualizing the microscopic effects of cosmetic procedures on skin anatomy., (© 2024 The Authors. Skin Research and Technology published by John Wiley & Sons Ltd.)

The mitotic spindle contains many bundles of microtubules (MTs) including midzones and kinetochore fibers, but little is known about how bundled structures are formed. Here, we show that the chromosomal passenger complex (CPC) purified from Escherichia coli undergoes liquid-liquid demixing in vitro. An emergent property of the resultant condensates is to generate parallel MT bundles when incubated with free tubulin and GTP in vitro. We demonstrate that MT bundles emerge from CPC droplets with protruding minus ends that then grow into long and tapered MT structures. During this growth, we found that the CPC in these condensates apparently reorganize to coat and bundle the resulting MT structures. CPC mutants attenuated for liquid-liquid demixing or MT binding prevented the generation of parallel MT bundles in vitro and reduced the number of MTs present at spindle midzones in HeLa cells. Our data demonstrate that an in vitro biochemical activity to produce MT bundles emerges after the concentration of the CPC and provides models for how cells generate parallel-bundled MT structures that are important for the assembly of the mitotic spindle. Moreover, these data suggest that cells contain MT-organizing centers that generate MT bundles that emerge with the opposite polarity from centrosomes., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Approximately 0.7% of patients taking angiotensin-converting enzyme inhibitors (ACEIs) develop ACEI-induced angioedema (ACEI-IA). With no approved treatments for ACEI-IA, the risk of complications is concerning. Tranexamic acid (TXA) has the potential to prevent intubations and resolve ACEI-IA by inhibiting the downstream production of bradykinin. In this review, we aim to evaluate the safety and efficacy of TXA use in ACEI-IA. We queried the PubMed database for studies involving TXA for ACEI-IA from January 2003 to January 2023. Seven studies met the study inclusion criteria. Our results demonstrate that TXA may improve angioedema symptoms and prevent intubation. In addition, its availability, low cost, and safety profile support its use for improving the symptoms and complications of ACEI-IA in an emergency setting.

Staining is a crucial step in histopathology that prepares tissue sections for microscopic examination. Hematoxylin and eosin (H&E) staining, also known as basic or routine staining, is used in 80% of histopathology slides worldwide. To enhance the histopathology workflow, recent research has focused on integrating generative artificial intelligence and deep learning models. These models have the potential to improve staining accuracy, reduce staining time, and minimize the use of hazardous chemicals, making histopathology a safer and more efficient field. In this study, we introduce a novel three-stage, dual contrastive learning-based, image-to-image generative (DCLGAN) model for virtually applying an "H&E stain" to unstained skin tissue images. The proposed model utilizes a unique learning setting comprising two pairs of generators and discriminators. By employing contrastive learning, our model maximizes the mutual information between traditional H&E-stained and virtually stained H&E patches. Our dataset consists of pairs of unstained and H&E-stained images, scanned with a brightfield microscope at 20 × magnification, providing a comprehensive set of training and testing images for evaluating the efficacy of our proposed model. Two metrics, Fréchet Inception Distance (FID) and Kernel Inception Distance (KID), were used to quantitatively evaluate virtual stained slides. Our analysis revealed that the average FID score between virtually stained and H&E-stained images (80.47) was considerably lower than that between unstained and virtually stained slides (342.01), and unstained and H&E stained (320.4) indicating a similarity virtual and H&E stains. Similarly, the mean KID score between H&E stained and virtually stained images (0.022) was significantly lower than the mean KID score between unstained and H&E stained (0.28) or unstained and virtually stained (0.31) images. In addition, a group of experienced dermatopathologists evaluated traditional and virtually stained images and demonstrated an average agreement of 78.8% and 90.2% for paired and single virtual stained image evaluations, respectively. Our study demonstrates that the proposed three-stage dual contrastive learning-based image-to-image generative model is effective in generating virtual stained images, as indicated by quantified parameters and grader evaluations. In addition, our findings suggest that GAN models have the potential to replace traditional H&E staining, which can reduce both time and environmental impact. This study highlights the promise of virtual staining as a viable alternative to traditional staining techniques in histopathology., (© 2024. The Author(s).)

Port-wine stains (PWS) are capillary vascular anomalies that are often treated with pulsed-dye laser (PDL). Revascularization limits persistent clearance; however, the anti-angiogenic effects of sirolimus (SIRO) may inhibit revascularization. This review aims to determine differences in PWS outcomes when treated with PDL monotherapy or in combination with SIRO. A systematic review was conducted using PubMed, Cochrane, and Embase databases. The following search terms were used: 'port wine stain PDL SIRO', 'port wine stain PDL', and 'port wine stain PDL and topical treatment' with (MeSH) and (Title/Abstract) limits. The search was limited to the English language and human-subject studies conducted between 1 January 2000 and 1 June 2023. Inclusion criteria included studies evaluating SIRO as an adjunct to PDL in patients with PWS. Data extraction and quality assessment were performed by two independent reviewers. A total of nine studies met the inclusion criteria, which included randomized controlled trials (3), case series (2), case reports (3), and a prospective intrapatient study (1), which represented a total of 58 patients. Five studies showed improvement of a measured post-treatment PDL parameter including shortening treatment time and less frequent dosing. A subset of studies (4/9) which did not demonstrate significant clinical improvements exhibited significant photographic evidence of improvement. Heterogeneity among the studies highlights the need for further research and standardization. While adjunctive SIRO shows promise, larger studies and comprehensive evaluation methods are required to establish conclusive safety and efficacy guidelines to shape clinical decision-making., Competing Interests: Dr. Rao is a speaker for Incyte. All other authors have no disclosures., (© 2024 The Authors. Skin Health and Disease published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)

Scleredema diabeticorum (SD) is a common cause of scleredema with limited effective treatment options available. Patients with SD may experience significant discomfort due to symptoms of itching, burning, or pain. SD typically develops due to poor glycaemic control as demonstrated in this case., Competing Interests: The authors declare no conflicts of interest., (© 2023 The Authors. Skin Health and Disease published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)

Porokeratosis is a rare group of acquired or hereditary dermatoses characterized by linear or annular plaques with a keratotic border. DSAP is the most common porokeratosis, and lesions range from asymptomatic to pruritic circular pink to brown macules, papules, or plaques surrounded by a raised border. DSAP carries about 7.5-10% risk of malignant transformation to SCC or BCC. While in the past DSAP has been widely treated with topical diclofenac, ingenol mebutate, topical vitamin D analog, 5-fluorouracil, imiquimod, photodynamic therapy, retinoids, cryotherapy, and laser therapy, these therapies have shown limited efficacy and have caused adverse effects including inflammatory reactions, hyperpigmentation, pain, and erythema. Recently, a formulation of topical statin and cholesterol has surfaced as a new and promising treatment for DSAP which has shown clinical improvement with a tolerable adverse effect profile when compared to the current therapies. Of the 8 case studies with a total of 20 patients with DSAP, 90% (18/20) reported clinical improvement with various forms of topical statin therapy. While promising, larger randomized controlled trials are needed to evaluate the long-term use of topical statins for DSAP. J Drugs Dermatol. 2023;22(10):&nbsp; &nbsp; &nbsp;doi:10.36849/JDD.7540.

Purpose: A rise in market demand for anti-aging skin care products has resulted in a proliferation of cosmeceuticals, including products that contain vitamin C. Many topicals containing vitamin C claim to reduce the appearance of wrinkles. However, these claims have not been systematically evaluated., Methods: A systematic review of literature published between January 2015 and September 2022 was performed per PRISMA guidelines. Scopus, Web of Science, and PubMed were queried for records relevant using the following Medical Subject Heading (MeSH) terms: &ldquo;Topical Vitamin C OR Ascorbic acid&rdquo;, &ldquo;Vitamin C efficacy&rdquo;, &ldquo;dermatology&rdquo;, &ldquo;cosmetology&rdquo;, and &ldquo;skin anti-aging&rdquo;. Variables of interest included: study type, study location, study duration, sample size, patient description, type and ingredients of the topical formulation, outcome measurement, results, and adverse events., Results: After deduplication, consideration of inclusion and exclusion criteria, and title/abstract screening, 5,428 initial records were reduced to 7 articles, including 4 meeting Level IB criteria, one meeting Level IIA criteria, and 2 meeting Level IIB criteria. Methods for assessing clinical improvements included global photodamage score, skin topography assessment, reflectance confocal microscopy (RCM) skin analysis, Dynamical Atlas, and participant self-assessment.&nbsp; Conclusions: While 4 of the 7 studies met Level IB evidence, further high-quality, prospective, and comparative studies are indicated to better elucidate the role of topical vitamin C in wrinkle reduction. All the studies used vitamin C in combination with other ingredients or therapeutic mechanisms, thereby complicating any specific conclusions regarding the efficacy of vitamin C.&nbsp;Citation: Sanabria B, Berger LE, Mohd H, et al. Clinical efficacy of topical vitamin C on the appearance of wrinkles: a systematic literature review. J Drugs Dermatol. 2023;22(9):898-904. doi:10.36849/JDD.7332.

Competing Interests: None disclosed.

Competing Interests: Dr Rao is a speaker for Incyte. All other authors have no disclosures.

Background: Vivascope 2500 ex vivo confocal microscopy (EVCM) is an emerging optical imaging device that allows nuclear level resolution of freshly excised tissues. EVCM provides, rapid real-time pathological examination in many subspecialties of pathology including skin, prostate, breast, liver, etc. In contrast to traditional time-consuming frozen sectioning and histological analysis., Aims: To evaluate the current state of EVCM utilization., Materials and Methods: This study highlights the advantages, limitations, and prospects of EVCM in skin pathology., Results: Our findings demonstrate that EVCM is a promising adjunctive tool to assess margins in Mohs surgery and to provide rapid, accurate diagnosis of cutaneous tumors, infectious and inflammatory diseases., Conclusion: EVCM is a revolutionary device that can be used as an adjunct to paraffin-fixed, hematoxylin and eosin-stained slides and frozen sectioning. Additional refinements are required before EVCM can be used as an alternative to frozen sectioning or traditional tissue processing., (© 2023 The Authors. Skin Research and Technology published by John Wiley & Sons Ltd.)

Voltage-gated potassium (Kv) channels formed by α subunits KCNQ2-5 are important in regulating neuronal excitability. We previously found that GABA directly binds to and activates channels containing KCNQ3, challenging the traditional understanding of inhibitory neurotransmission. To investigate the functional significance and behavioral role of this direct interaction, mice with a mutated KCNQ3 GABA binding site (Kcnq3-W266L) were generated and subjected to behavioral studies. Kcnq3-W266L mice exhibited distinctive behavioral phenotypes, of which reduced nociceptive and stress responses were profound and sex-specific. In female Kcnq3-W266L mice, the phenotype was shifted towards more nociceptive effects, while in male Kcnq3-W266L mice, it was shifted towards the stress response. In addition, female Kcnq3-W266L mice exhibited lower motor activity and reduced working spatial memory. The neuronal activity in the lateral habenula and visual cortex was altered in the female Kcnq3-W266L mice, suggesting that GABAergic activation of KCNQ3 in these regions may play a role in the regulation of the responses. Given the known overlap between the nociceptive and stress brain circuits, our data provide new insights into a sex-dependent role of KCNQ3 in regulating neural circuits involved in nociception and stress, via its GABA binding site. These findings identify new targets for effective treatments for neurological and psychiatric conditions such as pain and anxiety., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Chen, Yoshimura, Edmundo, Truong, Civelli, Alachkar and Abbott.)

Objectives: Hypopharyngeal and laryngeal cancers are aggressive and usually diagnosed at advanced stage with esophagus invasion. Total pharyngolaryngoesophagectomy with gastric pull-up reconstruction has been a common surgery for these cancers but long-term outcomes are still questionable. This study aimed to investigate short-term and long-term outcomes of patients who underwent this surgery., Methods: Patients with hypopharyngeal or laryngeal cancer invading cervical esophagus who underwent total pharyngolaryngoesphagectomy with gastric pull-up between 2012 and 2016 was included and followed up until 2021. Short-term outcomes were complications and long-term outcomes were overall survival (OS) and disease-free survival (DFS)., Results: Fifty patients were included with a mean age of 60.3 years and 94% were male. Pyriform fossa was the most common primary site of tumor (50%), followed by posterior hypopharyngeal wall (18%) and postcricoid region (18%). Mean operating time, postoperative oral intake and hospital stay was 363.1 ± 43.6 minutes, 8.8 ± 3.6 days and 14.2 ± 3.0 days respectively. Complications occurred in 15 patients (30%) without any in-hospital death. During the follow-up period, 17 patients had recurrence and 35 patients died. Median (95% confidence interval [CI]) OS and DFS time were 30 (21-37) and 30 (19-36) months. Five-year OS and DFS probability (95% CI) were 22.6% (12.8-39.7) and 22.7% (12.9-39.8)., Conclusions: Total pharyngolaryngoesophagectomy with gastric pull-up is feasible and safe. However, even with curative surgery and multimodal treatment, advanced pharyngeal or laryngeal cancer with cervical esophagus invasion still has poor survival outcome.

Competing Interests: None disclosed.

Background: Pharmacogenomics, which offers a potential means by which to inform prescribing and avoid adverse drug reactions, has gained increasing consideration in other medical settings but has not been broadly evaluated during perioperative care., Methods: The Implementation of Pharmacogenomic Decision Support in Surgery (ImPreSS) Trial is a prospective, single-center study consisting of a prerandomization pilot and a subsequent randomized phase. We describe findings from the pilot period. Patients planning elective surgeries were genotyped with pharmacogenomic results, and decision support was made available to anesthesia providers in advance of surgery. Pharmacogenomic result access and prescribing records were analyzed. Surveys (Likert-scale) were administered to providers to understand utilization barriers., Results: Of eligible anesthesiology providers, 166 of 211 (79%) enrolled. A total of 71 patients underwent genotyping and surgery (median, 62 years; 55% female; average American Society of Anesthesiologists (ASA) score, 2.6; 58 inpatients and 13 ambulatories). No patients required postoperative intensive care or pain consultations. At least 1 provider accessed pharmacogenomic results before or during 41 of 71 surgeries (58%). Faculty were more likely to access results (78%) compared to house staff (41%; P = .003) and midlevel practitioners (15%) ( P < .0001). Notably, all administered intraoperative medications had favorable genomic results with the exception of succinylcholine administration to 1 patient with genomically increased risk for prolonged apnea (without adverse outcome). Considering composite prescribing in preoperative, recovery, throughout hospitalization, and at discharge, each patient was prescribed a median of 35 (range 15-83) total medications, 7 (range 1-22) of which had annotated pharmacogenomic results. Of 2371 prescribing events, 5 genomically high-risk medications were administered (all tramadol or omeprazole; with 2 of 5 pharmacogenomic results accessed), and 100 genomically cautionary mediations were administered (hydralazine, oxycodone, and pantoprazole; 61% rate of accessing results). Providers reported that although results were generally easy to access and understand, the most common reason for not considering results was because remembering to access pharmacogenomic information was not yet a part of their normal clinical workflow., Conclusions: Our pilot data for result access rates suggest interest in pharmacogenomics by anesthesia providers, even if opportunities to alter prescribing in response to high-risk genotypes were infrequent. This pilot phase has also uncovered unique considerations for implementing pharmacogenomic information in the perioperative care setting, and new strategies including adding the involvement of surgery teams, targeting patients likely to need intensive care and dedicated pain care, and embedding pharmacists within rounding models will be incorporated in the follow-on randomized phase to increase engagement and likelihood of affecting prescribing decisions and clinical outcomes., Competing Interests: Conflicts of Interest: See Disclosures at the end of the article., (Copyright © 2022 International Anesthesia Research Society.)

The simultaneous occurrence of the COVID-19 pandemic and the transition to adulthood have posed particular obstacles to university students' mental health. However, it remains unclear whether hope promotes mental health in the relationship between self-compassion, psychological well-being, and life satisfaction. Therefore, this study investigated the role of hope as a mediator in the relationship between self-compassion, psychological well-being, and life satisfaction among Vietnamese undergraduate students in the context of the COVID-19 pandemic. Participants consisted of 484 students (aged 18-24) from several universities in Vietnam. To measure the four variables in the research model, we opted for the Self-Compassion Scale, the State Hope Scale, the World Health Organization 5-item Well-Being Index, and the Satisfaction With Life Scale. The results showed that (1) self-compassion was significantly positively correlated with psychological well-being, (2) self-compassion was not correlated with life satisfaction, (3) hope was a mediator of the relationship between self-compassion and psychological well-being, and (4) hope was a mediator of the relationship between self-compassion and life satisfaction. These findings suggest interventions on self-compassion to enhance hope and subsequently increase students' mental health, which offers colleges, psychologists, and psychiatrists a guideline to cope with harmful psychological implications during the COVID-19 pandemic., Competing Interests: Conflict of interestThe author(s) declared no potential conflicts of interest concerning the research, authorship, and/or publication of this article. On behalf of all authors, the corresponding author states that there is no conflict of interest., (© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

By applying the protection motivation theory, the study aims to investigate factors influencing tourism and hospitality (T&H) workers' career resilience when faced with health-related risks at work during a pandemic. Data were collected from 495 part-time and full-time employees in the Vietnamese tourism and hospitality sector. The study found that workers' perceived vulnerability and perceived severity of the pandemic were positively associated with career resilience. Perceived severity was positively related to self-efficacy and response efficacy, while perceived vulnerability was positively associated with self-efficacy only. Both self-efficacy and response efficacy positively influenced career resilience through the mediating role of health risk preventative behavior. Theoretically, the study advances the stream of research in resilience in general and career resilience in particular among T&H workers when faced with a health-related crisis. Practical implications are provided with recommendations on how to facilitate career resilience among T&H employees working in the current high-risk environment., (© 2022 Elsevier Ltd. All rights reserved.)

Background: In recent years, there has been increasing evidence supporting the role of germline pharmacogenomic factors predicting toxicity for anticancer therapies. Although somatic genomic data are used frequently in oncology care planning, germline pharmacogenomic testing is not. This study hypothesizes that comprehensive germline pharmacogenomic profiling could have high relevance for cancer care., Methods: Between January 2011 and August 2020, patients at the University of Chicago Medical Center were genotyped across custom germline pharmacogenomic panels for reasons unrelated to cancer care. Actionable anticancer pharmacogenomic gene/drug interactions identified by the FDA were defined including: CYP2C9 (erdafitinib), CYP2D6 (gefitinib), DPYD (5-fluorouracil and capecitabine), TPMT (thioguanine and mercaptopurine), and UGT1A1 (belinostat, irinotecan, nilotinib, pazopanib, and sacituzumab-govitecan hziy). The primary objective was to determine the frequency of individuals with actionable or high-risk genotypes across these 5 key pharmacogenes, thus potentially impacting prescribing for at least 1 of these 11 commonly prescribed anticancer therapies., Results: Data from a total of 1586 genotyped individuals were analyzed. The oncology pharmacogene with the highest prevalence of high-risk, actionable genotypes was UGT1A1, impacting 17% of genotyped individuals. Actionable TPMT and DPYD genotypes were found in 9% and 4% of patients, respectively. Overall, nearly one-third of patients genotyped across all 5 genes (161/525, 31%) had at least one actionable genotype., Conclusions: These data suggest that germline pharmacogenomic testing for 5 key pharmacogenes could identify a substantial proportion of patients at risk with standard dosing, an estimated impact similar to that of somatic genomic profiling., Lay Summary: Differences in our genes may explain why some drugs work safely in certain individuals but can cause side effects in others. Pharmacogenomics is the study of how genetic variations affect an individual's response to medications. In this study, an evaluation was done for important genetic variations that can affect the tolerability of anticancer therapy. By analyzing the genetic results of >1500 patients, it was found that nearly one-third have genetic variations that could alter recommendations of what drug, or how much of, an anticancer therapy they should be given. Performing pharmacogenomic testing before prescribing could help to guide personalized oncology care., (© 2022 American Cancer Society.)

Objectives: Integration of pharmacogenomics into clinical care is being studied in multiple disciplines. We hypothesized that understanding attitudes and perceptions of anesthesiologists, critical care and pain medicine providers would uncover unique considerations for future implementation within perioperative care., Methods: A survey (multiple choice and Likert-scale) was administered to providers within our Department of Anesthesia and Critical Care prior to initiation of a department-wide prospective pharmacogenomics implementation program. The survey addressed knowledge, perceptions, experiences, resources and barriers., Results: Of 153 providers contacted, 149 (97%) completed the survey. Almost all providers (92%) said that genetic results influence drug therapy, and few (22%) were skeptical about the usefulness of pharmacogenomics. Despite this enthusiasm, 87% said their awareness about pharmacogenomic information is lacking. Feeling well-informed about pharmacogenomics was directly related to years in practice/experience: only 38% of trainees reported being well-informed, compared to 46% of those with 1-10 years of experience, and nearly two-thirds with 11+ years (P < 0.05). Regarding barriers, providers reported uncertainty about availability of testing, turnaround time and whether testing is worth financial costs., Conclusions: Anesthesiology, critical care and pain medicine providers are optimistic about the potential clinical utility of pharmacogenomics, but are uncertain about practical aspects of testing and desire clear guidelines on the use of results. These findings may inform future institutional efforts toward greater integration of genomic results to improve medication-related outcomes., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Variable responses to medications complicates perioperative care. As a potential solution, we evaluated and synthesized pharmacogenomic evidence that may inform anesthesia and pain prescribing to identify clinically actionable drug/gene pairs. Clinical decision-support (CDS) summaries were developed and were evaluated using Appraisal of Guidelines for Research and Evaluation (AGREE) II. We found that 93/180 (51%) of commonly-used perioperative medications had some published pharmacogenomic information, with 18 having actionable evidence: celecoxib/diclofenac/flurbiprofen/ibuprofen/piroxicam/CYP2C9, codeine/oxycodone/tramadol CYP2D6, desflurane/enflurane/halothane/isoflurane/sevoflurane/succinylcholine/RYR1/CACNA1S, diazepam/CYP2C19, phenytoin/CYP2C9, succinylcholine/mivacurium/BCHE, and morphine/OPRM1. Novel CDS summaries were developed for these 18 medications. AGREE II mean ± standard deviation scores were high for Scope and Purpose (95.0 ± 2.8), Rigor of Development (93.2 ± 2.8), Clarity of Presentation (87.3 ± 3.0), and Applicability (86.5 ± 3.7) (maximum score = 100). Overall mean guideline quality score was 6.7 ± 0.2 (maximum score = 7). All summaries were recommended for clinical implementation. A critical mass of pharmacogenomic evidence exists for select medications commonly used in the perioperative setting, warranting prospective examination for clinical utility., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Several opioids have pharmacogenomic associations impacting analgesic efficacy. However, germline pharmacogenomic testing is not routinely incorporated into supportive oncology. We hypothesized that CYP2D6 profiling would correlate with opioid prescribing and hospitalizations., Materials and Methods: We analyzed 61,572 adult oncology patients from 2012 to 2018 for opioid exposures. CYP2D6 metabolizer phenotype (ultra-rapid [UM], normal metabolizer [NM], intermediate [IM], or poor [PM]), the latter two of which may cause inefficacy of codeine, tramadol, and standard-dose hydrocodone, was determined for patients genotyped for reasons unrelated to pain. The primary endpoint was number of opioid medications received during longitudinal care (IM/PMs vs. NMs). Secondary endpoint was likelihood of pain-related hospital encounters., Results: Most patients with cancer (n = 34,675, 56%) received multiple opioids (average 2.8 ± 1.6/patient). Hydrocodone was most commonly prescribed (62%), followed by tramadol, oxycodone, and codeine. In the CYP2D6 genotyped cohort (n = 105), IM/PMs received a similar number of opioids (3.4 ± 1.4) as NMs (3.3 ± 1.9). However, IM/PMs were significantly more likely to experience pain-related hospital encounters compared with NMs, independent of other variables (odds ratio [OR] = 5.4; 95% confidence interval [CI], 1.2-23.6; p = .03). IM/PMs were also more likely to be treated with later-line opioids that do not require CYP2D6 metabolism, such as morphine and hydromorphone (OR = 3.3; 95% CI, 1.1-9.8; p = .03)., Conclusion: CYP2D6 genotype may identify patients with cancer at increased risk for inadequate analgesia when treated with typical first-line opioids like codeine, tramadol, or standard-dose hydrocodone. Palliative care considerations are an integral part of optimal oncology care, and these findings justify prospective evaluation of preemptive genotyping as a strategy to improve oncology pain management., Implications for Practice: Genomic variation in metabolic enzymes can predispose individuals to inefficacy when receiving opioid pain medications. Patients with intermediate and/or poor CYP2D6 metabolizer status do not adequately convert codeine, tramadol, and hydrocodone into active compounds, with resulting increased risk of inadequate analgesia. This study showed that patients with cancer frequently receive CYP2D6-dependent opioids. However, patients with CYP2D6 intermediate and poor metabolizer status had increased numbers of pain-related hospitalizations and more frequently required the potent non-CYP2D6 opioids morphine and hydromorphone. This may reflect inadequate initial analgesia with the common "first-line" CYP2D6-metabolized opioids. Preemptive genotyping to guide opioid prescribing during cancer care may improve pain-related patient outcomes., (© 2021 AlphaMed Press.)

G-protein-coupled receptors (GPCRs) play an integral role in the neurobiology of psychiatric disorders. Almost all neurotransmitters involved in psychiatric disorders act through GPCRs, and GPCRs are the most common targets of therapeutic drugs currently used in the treatment of psychiatric disorders. However, the roles of GPCRs in the etiology and pathophysiology of psychiatric disorders are not fully understood. Using publically available datasets, we performed a comprehensive analysis of the transcriptomic signatures of G-protein-linked signaling across the major psychiatric disorders: autism spectrum disorder (ASD), schizophrenia (SCZ), bipolar disorder (BP), and major depressive disorder (MDD). We also used the BrainSpan transcriptomic dataset of the developing human brain to examine whether GPCRs that exhibit chronological age-associated expressions have a higher tendency to be dysregulated in psychiatric disorders than age-independent GPCRs. We found that most GPCR genes were differentially expressed in the four disorders and that the GPCR superfamily as a gene cluster was overrepresented in the four disorders. We also identified a greater amplitude of gene expression changes in GPCRs than other gene families in the four psychiatric disorders. Further, dysregulated GPCRs overlapped across the four psychiatric disorders, with SCZ exhibiting the highest overlap with the three other disorders. Finally, the results revealed a greater tendency of age-associated GPCRs to be dysregulated in ASD than random GPCRs. Our results substantiate the central role of GPCR signaling pathways in the etiology and pathophysiology of psychiatric disorders. Furthermore, our study suggests that common GPCRs' signaling may mediate distinct phenotypic presentations across psychiatric disorders. Consequently, targeting these GPCRs could serve as a common therapeutic strategy to treat specific clinical symptoms across psychiatric disorders.

Background: Applied pharmacogenomics presents opportunities for improving patient care through precision medicine, particularly when paired with appropriate clinical decision support (CDS). However, a lack of patient resources for understanding pharmacogenomic test results may hinder shared decision-making and patient confidence in treatment. We sought to create a patient pharmacogenomics education and results delivery platform complementary to a CDS system to facilitate further research on the relevance of patient education to pharmacogenomics., Methods: We conceptualized a model that extended the data access layer of an existing institutional CDS tool to allow for the pairing of decision supports offered to providers with patient-oriented summaries at the same level of phenotypic specificity. We built a two-part system consisting of a secure portal for patient use and an administrative dashboard for patient summary creation. The system was built in an ASP.NET and AngularJS architecture, and all data was housed in a HIPAA-compliant data center, with PHI secure in transit and at rest., Results: The YourPGx Patient Portal was deployed on the institutional network in June 2019. Fifty-eight unique patient portal summaries have been written so far, which can provide over 4500 results modules to the pilot population of 544 patients. Patient behavior on the portal is being logged for further research., Conclusions: To our knowledge, this is the first automated system designed and deployed to provide detailed, personalized patient pharmacogenomics education complementary to a clinical decision support system. Future work will expand upon this system to allow for telemedicine and patient notification of new or updated results., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Medical Informatics Association.)

Neurometabolites are the ultimate gene products in the brain and the most precise biomolecular indicators of brain endophenotypes. Metabolomics is the only "omics" that provides a moment-to-moment "snapshot" of brain circuits' biochemical activities in response to external stimuli within the context of specific genetic variations. Although the expression levels of neurometabolites are highly dynamic, the underlying metabolic processes are tightly regulated during brain development, maturation, and aging. Therefore, this study aimed to identify mouse brain metabolic profiles in neonatal and adult stages and reconstruct both the active metabolic network and the metabolic pathway functioning. Using high-throughput metabolomics and bioinformatics analyses, we show that the neonatal mouse brain has its distinct metabolomic signature, which differs from the adult brain. Furthermore, lipid metabolites showed the most profound changes between the neonatal and adult brain, with some lipid species reaching 1000-fold changes. There were trends of age-dependent increases and decreases among lipids and non-lipid metabolites, respectively. A few lipid metabolites such as HexCers and SHexCers were almost absent in neonatal brains, whereas other non-lipid metabolites such as homoarginine were absent in the adult brains. Several molecules that act as neurotransmitters/neuromodulators showed age-dependent levels, with adenosine and GABA exhibiting around 100- and 10-fold increases in the adult compared with the neonatal brain. Of particular interest is the observation that purine and pyrimidines nucleobases exhibited opposite age-dependent changes. Bioinformatics analysis revealed an enrichment of lipid biosynthesis pathways in metabolites, whose levels increased in adult brains. In contrast, pathways involved in the metabolism of amino acids, nucleobases, glucose (glycolysis), tricarboxylic acid cycle (TCA) were enriched in metabolites whose levels were higher in the neonatal brains. Many of these pathways are associated with pathological conditions, which can be predicted as early as the neonatal stage. Our study provides an initial age-related biochemical directory of the mouse brain and warrants further studies to identify temporal brain metabolome across the lifespan, particularly during adolescence and aging. Such neurometabolomic data may provide important insight about the onset and progression of neurological/psychiatric disorders and may ultimately lead to the development of precise diagnostic biomarkers and more effective preventive/therapeutic strategies.

Background: Many cancer patients who receive chemotherapy experience adverse drug effects. Pharmacogenomics (PGx) has promise to personalize chemotherapy drug dosing to maximize efficacy and safety. Fluoropyrimidines and irinotecan have well-known germline PGx associations. At our institution, we have delivered PGx clinical decision support (CDS) based on preemptively obtained genotyping results for a large number of non-oncology medications since 2012, but have not previously evaluated the utility of this strategy for patients initiating anti-cancer regimens. We hypothesize that providing oncologists with preemptive germline PGx information along with CDS will enable individualized dosing decisions and result in improved patient outcomes., Methods: Patients with oncologic malignancies for whom fluoropyrimidine and/or irinotecan-inclusive therapy is being planned will be enrolled and randomly assigned to PGx and control arms. Patients will be genotyped in a clinical laboratory across panels that include actionable variants in UGT1A1 and DPYD . For PGx arm patients, treating providers will be given access to the patient-specific PGx results with CDS prior to treatment initiation. In the control arm, genotyping will be deferred, and dosing will occur as per usual care. Co-primary endpoints are dose intensity deviation rate (the proportion of patients receiving dose modifications during the first treatment cycle), and grade ⩾3 treatment-related toxicities throughout the treatment course. Additional study endpoints will include cumulative drug dose intensity, progression-free survival, dosing of additional PGx supportive medications, and patient-reported quality of life and understanding of PGx., Discussion: Providing a platform of integrated germline PGx information may promote personalized chemotherapy dosing decisions and establish a new model of care to optimize oncology treatment planning., Competing Interests: Conflict of interest statement: M.J. Ratain is a coinventor holding patents related to pharmacogenetic diagnostics and receives royalties related to UGT1A1 genotyping., (© The Author(s), 2020.)

Objectives: We built a novel mock pharmacogenomics web portal to deliver pharmacogenomic information and results to patients. Utilizing a patient focus group, we then sought to understand patient insights on desired features of an effective pharmacogenomics patient portal., Methods: The mock YourPGx Portal delivered four sample pharmacogenomic results (omeprazole, simvastatin, clopidogrel, and codeine). Patients from our existing institutional, prospective pharmacogenomics implementation study were recruited to pilot the mock portal and then asked to participate in a focus group discussion led by two facilitators. All patients had been previously genotyped, but none had been directly provided access to their own genotyping results and none had previously used the YourPGx portal. The focus group discussion explored nine domains: (1) factors influencing drug response, (2) concerns about drug effects, (3) understanding of genomics and pharmacogenomics, (4) reasons to undergo pharmacogenomic testing, (5) sources of pharmacogenomic information for patient education, (6) attributes of pharmacogenomic sources of information, (7) considerations about privacy and personal pharmacogenomic information, (8) sharing of pharmacogenomic information, and (9) features of an effective patient portal., Results: The median age of patients (n = 10) was 65.5 years old (range 38-72), 70% female, 50% Caucasian/30% Black, and 60% held a bachelor/advanced degree. When asked about resources for seeking pharmacogenomic information, patients preferred consulting their providers first, followed by self-education, then using information provided by university research organizations. A theme emerged regarding attributes of these sources, namely a desire for understandability and trust. Patients said that the effectiveness of a pharmacogenomics patient portal is improved with use of symbolisms/graphics and clear and concise content. Effective use of colors, quantifying information, consistency, and use of layperson's language were additional important facets. Patients communicated the appeal of secured phone/app-enabled access and said that they would desire linking to their electronic medical records to allow sharing of information with different members of their healthcare team., Conclusions: Patients named providers as their primary source of pharmacogenomic information, but a pharmacogenomics patient portal that is carefully constructed to incorporate desired features may be a favorable tool to effectively deliver pharmacogenomic information and results to patients.

Our objective was to build a mock pharmacogenomic (PGx) patient portal and assess its ability to disseminate test results and information to patients. The YourPGx Portal delivered four sample PGx results (omeprazole, simvastatin, clopidogrel, and codeine). We hosted two study groups to assess patient knowledge and perceptions of PGx before and after accessing the portal. Ten PGx-tested and 10 traditional care participants were included (average 61 years, 60% women, 50% African American, and 55% had a bachelor's/advanced degree). Participants scored significantly higher on the post-test compared with the pre-test, with no significant differences between baseline scores or score change between the groups. Patient perceptions also improved after accessing the portal-more patients wanted their providers to have access to test results, and more patients would encourage family/friends to get PGx testing. Patients would share their test results with their healthcare providers, spouse/partner, and family; none would share results with their friends or social media. Almost all patients (95%) said the portal was easy to use and 65% said it was easy to understand. In this pilot study, patients' knowledge and perceptions of PGx improved after accessing the YourPGx Portal., (© 2019 The Authors. Clinical and Translational Science published by Wiley Periodicals, Inc. on behalf of the American Society for Clinical Pharmacology and Therapeutics.)

Child stunting in Vietnam has reduced substantially since the turn of the century but has remained relatively high for several years. We analysed data on children 6-59 months (n = 85,932) from the Vietnam Nutritional Surveillance System, a nationally representative cross-sectional survey. Multivariable Poisson regression models were used to estimate relative risk (RR) of stunting, stratified by child age and ecological region. Covariates at the child, maternal, household, and environmental levels were included based on available data and the World Health Organization conceptual framework on child stunting. Among children 6-23 months, the strongest associations with child stunting were child age in years (RR: 2.49; 95% CI [2.26, 2.73]), maternal height < 145 cm compared with ≥150 cm (RR: 2.04; 95% CI [1.85, 2.26]), living in the Northeast compared with the Southeast (RR: 2.01; 95% CI [1.69, 2.39]), no maternal education compared with a graduate education (RR: 1.77; 95% CI, [1.44, 2.16]), and birthweight < 2,500 g (RR: 1.75; 95% CI [1.55, 1.98]). For children 24-59 months, the strongest associations with child stunting were no maternal education compared with a graduate education (RR: 2.07; 95% CI [1.79, 2.40]), living in the Northeast compared with the Southeast (RR: 1.94; 95% CI [1.74, 2.16]), and maternal height < 145 cm compared with ≥150 cm (RR: 1.81; 95% CI [1.69, 1.94]). Targeted approaches that address the strongest stunting determinants among vulnerable populations are needed and discussed. Multifaceted approaches outside the health sector are also needed to reduce inequalities in socioeconomic status., (© 2019 John Wiley & Sons Ltd.)

Induced lung cell death and impaired hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) signaling are proposed as a pathobiologic mechanism for alveolar structural destruction and loss in emphysema. We hypothesized that our sulfated dehydropolymer of caffeic acid, CDSO3, exerts anti-cell death activities and therapeutic interventions in emphysema by virtue of Fe 2+ chelation-based HIF-1α/VEGF stabilization and elevation. The Fe 2+ chelating activity was determined in the chromogenic ferrozine-Fe 2+ chelation inhibitory assay. The in vitro anti-cell death activities and their Fe 2+ and HIF-1α dependence were assessed against a range of emphysematous insults in the lung endothelial (HMVEC-L) and epithelial (A549) cells. CDSO3 was spray-dosed to the lung for three weeks (day 1-21) in an in vivo rat model of apoptotic emphysema induced with a VEGF receptor antagonist SU5416. Post-treatment treadmill exercise endurance, airspace enlargement, and several lung biomarkers/proteins were measured. CDSO3 was a potent Fe 2+ chelating molecule. At 10 μM, CDSO3 inhibited HMVEC-L and A549 cell death induced by histone deacetylase inhibition with trichostatin A, VEGF receptor blockade with SU5416, and cigarette smoke extract by 65-99%, which were all significantly opposed by addition of excess Fe 2+ or HIF-1α inhibitors. As a potent elastase inhibitor and antioxidant, CDSO3 also inhibited elastase- and H 2 O 2 -induced cell death by 92 and 95%, respectively. In the rat model of SU5416-induced apoptotic emphysema, CDSO3 treatment at 60 μg/kg 1) produced 61-77% interventions against exercise endurance impairment, airspace enlargement [mean linear intercept] and oxidative lung damage [malondialdehyde activity]; 2) normalized the apoptotic marker [cleaved caspase-3]; 3) stimulated the VEGF signaling [VEGF receptor 2 phosphorylation] by 1.4-fold; and 4) elevated the HIF-1α and VEGF expression by 1.8- and 1.5-fold, respectively. All of these were consistent with CDSO3's Fe 2+ chelation-based HIF-1α/VEGF stabilization and elevation against their pathobiologic deficiency, inhibiting lung cell death and development of apoptotic emphysema., (Copyright © 2017. Published by Elsevier Ltd.)

Fluorescent protein-based biosensors are indispensable molecular tools for life science research. The invention and development of high-fidelity biosensors for a particular molecule or molecular event often catalyze important scientific breakthroughs. Understanding the structural and functional organization of brain activities remain a subject for which optical sensors are in desperate need and of growing interest. Here, we review genetically encoded fluorescent sensors for imaging neuronal activities with a focus on the design principles and optimizations of various sensors. New bioluminescent sensors useful for deep-tissue imaging are also discussed. By highlighting the protein engineering efforts and experimental applications of these sensors, we can consequently analyze factors influencing their performance. Finally, we remark on how future developments can fill technological gaps and lead to new discoveries., Competing Interests: Conflicts of Interest: The authors declare no conflict of interest.