Mitochondrial complex III is essential for suppressive function of regulatory T cells.

Regulatory T cells (Treg cells), a distinct subset of CD4+ T cells, are necessary for the maintenance of immune self-tolerance and homeostasis1,2. Recent studies have demonstrated that Treg cells exhibit a unique metabolic profile, characterized by an increase in mitochondrial metabolism relative to other CD4+ effector subsets3,4. Furthermore, the Treg cell lineage-defining transcription factor, Foxp3, has been shown to promote respiration5,6; however, it remains unknown whether the mitochondrial respiratory chain is required for the T cell-suppression capacity, stability and survival of Treg cells. Here we report that Treg cell-specific ablation of mitochondrial respiratory chain complex III in mice results in the development of fatal inflammatory disease early in life, without affecting Treg cell number. Mice that lack mitochondrial complex III specifically in Treg cells displayed a loss of T cell-suppression capacity without altering Treg cell proliferation and survival. Treg cells deficient in complex III showed decreased expression of genes associated with Treg function, whereas Foxp3 expression remained stable. Loss of complex III in Treg cells increased DNA methylation as well as the metabolites 2-hydroxyglutarate (2-HG) and succinate that inhibit the ten-eleven translocation (TET) family of DNA demethylases7. Thus, Treg cells require mitochondrial complex III to maintain immune regulatory gene expression and suppressive function.

TCA Cycle and Mitochondrial Membrane Potential Are Necessary for Diverse Biological Functions.

Mitochondrial metabolism is necessary for the maintenance of oxidative TCA cycle function and mitochondrial membrane potential. Previous attempts to decipher whether mitochondria are necessary for biological outcomes have been hampered by genetic and pharmacologic methods that simultaneously disrupt multiple functions linked to mitochondrial metabolism. Here, we report that inducible depletion of mitochondrial DNA (ρ(ο) cells) diminished respiration, oxidative TCA cycle function, and the mitochondrial membrane potential, resulting in diminished cell proliferation, hypoxic activation of HIF-1, and specific histone acetylation marks. Genetic reconstitution only of the oxidative TCA cycle function specifically in these inducible ρ(ο) cells restored metabolites, resulting in re-establishment of histone acetylation. In contrast, genetic reconstitution of the mitochondrial membrane potential restored ROS, which were necessary for hypoxic activation of HIF-1 and cell proliferation. These results indicate that distinct mitochondrial functions associated with respiration are necessary for cell proliferation, epigenetics, and HIF-1 activation.

Tips, Trends, and Truths: A Study of Psoriasis Treatment Content on TikTok.

INTRODUCTION: With more than two billion downloads since its launch, TikTok is the fastest-growing video-sharing platform in the world. Many people turn to TikTok for dermatologic medical information. However, there is limited data about psoriasis and psoriasis treatment content on this social media platform. OBJECTIVE: To compare the viewer engagement, content quality, and viewer experience of psoriasis treatment TikTok videos between physicians and non-physicians. METHODS: We searched the terms "psoriasis" and "psoriasis treatment" on TikTok. Video characteristics were collected. Content quality was evaluated using DISCERN. Viewer experience was assessed using the AVA. RESULTS: Viewer engagement did not significantly differ between physicians and non-physician content creators (0.033 plus/minus 0.005 vs 0.047 plus/minus 0.001, P=0.066). Compared to non-physicians, physicians created videos of higher quality (DISCERN: 1.76 plus/minus 0.058 vs 1.44 plus/minus 0.032, P<0.001) and of greater viewer experience (AVA: 2.55 plus/minus 0.183 vs 1.96 plus/minus 0.081, P=0.001). However, there is room for improvement in terms of creating videos of higher quality by both physicians and non-physicians. CONCLUSION: TikTok can be a powerful tool to promote health literacy and dispel misinformation. Dermatologists may consider focusing their efforts on creating comprehensive educational content and incorporating trending features to reach a wider audience. J Drugs Dermatol. 2024;23(2): doi:10.36849/JDD.7050e.

Evaluating Sentiment, Engagement, and Perception of Biologics Among Patients with Psoriasis and Psoriatic Arthritis on Reddit.

BACKGROUND: Limited analyses of social media content among psoriasis (PsO) and psoriatic arthritis (PsA) patients exist. These patients may turn to social media to gain insight into treatments such as biologics. OBJECTIVES: This study aims to analyze the content, sentiment, and engagement of social media posts regarding biologics for PsO and PsA. METHODS: Posts and comments discussing biologics were extracted from publicly accessible PsO and PsA Reddit groups. Posts were assigned higher (HOT) and lower order (LOT) themes, sentiments, and engagement scores. RESULTS: Of 1141 posts extracted, 705 posts were classified under the HOT general/efficacy. Twelve lower order themes (LOTs) were identified: general advice/experience (10.2%), symptoms improved (36.6%), switching biologics (10.5%), and time to results (13.4%). 61.3% of content was of positive sentiment, 24.0% was neutral, and 14.7% was of negative sentiment. The mean sentiment score, defined as the average of all posts' sentiment scores (where negative=-1, neutral=0, and positive=1), was overall positive at 0.47, 95% CI [.41-.52]. Mean sentiment scores between LOTs were significantly different (P<0.001). Information regarding biologics on Reddit is mostly positive; however, there remains a significant number of users expressing dissatisfaction with their efficacy or with biologics in general. Many users sought anecdotal advice. CONCLUSION: These findings can help guide educational efforts to anticipate concerns and appease hesitancy regarding biologics and their efficacy. J Drugs Dermatol. 2023;22(3):306-309. doi:10.36849/JDD.7124.

No Racial Differences Found in Access to Biologics: A Population-Based Study of Psoriasis Patients in the United States.

BACKGROUND: Conflicting evidence exists regarding the role of race in access to biologics for patients with psoriasis. OBJECTIVE: To compare biologic use among adult and pediatric United States psoriasis patients of different racial backgrounds. METHODS: Population-based study of US psoriasis patients using the 2003 to 2018 Medical Expenditure Panel Survey (MEPS). RESULTS: Among 31,525,500 adults and children with psoriasis (weighted), 3,026,578 (9.6%) were on biologics. Among psoriasis patients, 27,464,864 (87.1%) self-identified as white, 2,033,802 (6.5%) self-identified as Black, 1,173,435 (3.7%) self-identified as Asian or Pacific Islander, and 853,399 (2.7%) self-identified as other races. Among those on biologics, 2,778,239 (91.8%) self-identified as white, 84,971 (2.8%) identified as Black, 89,452 (3.0%) self-identified as Asian or Pacific Islander, and 73,917 (2.4%) self-identified as other races. Multivariate logistic regression revealed no significant differences in biologic access between whites and non-whites after adjusting for sociodemographic factors including insurance status (OR for Blacks: 0.347 [0.118, 1.021], P=0.055; OR for Asians: 0.616 [0.240, 1.579], P=0.311; OR for other races: 0.850 [0.216, 3.336], P=0.814. CONCLUSION: The results of this study suggest that race alone is not independently associated with access to biologics among adult US psoriasis patients. Additional studies are necessary to evaluate factors independently associated with biologics access among adults and children with psoriasis in the US. J Drugs Dermatol. 2023;22(8):835-837. doi:10.36849/JDD.7134 Reddy R, Khan S, Yee D, et al. No racial differences found in access to biologics: a population-based study of psoriasis patients in the United States. .

Differences in accessing dermatology offices, primary care offices, and emergency departments between Hispanics and Non-Hispanic White Patients.

How Hispanic patients access dermatologic care for skin diseases is unknown. This study aims to determine if differences exist in accessing the emergency department (ED), primary care, and outpatient dermatologic offices for skin diseases between Hispanic and non-Hispanic White patients. This cross-sectional study used nationally representative data from the Medical Panel Expenditure Survey (MEPS) from 2016-2019. A total of 109,337,668 (weighted) patients with any skin disease diagnosed at an ED, primary care, or dermatology visit were identified. Hispanics comprised 13.0% and non-Hispanic Whites comprised 68.8% of this subpopulation. Overall, 94.1% of Hispanic patients attended a primary care visit for their skin complaint, 5.8% saw a dermatologist, and 0.1% attended an ED visit. Compared to non-Hispanic Whites, Hispanics were more likely to attend a primary care visit (aOR 1.865; 95%CI, 1.640-2.122) and less likely to attend an outpatient dermatology visit (aOR 0.536; 95%CI, 0.471-0.610), after adjusting for insurance status, education, income, sex, age, and comorbidities. Our study suggests that, compared to non-Hispanic Whites, Hispanic patients access primary care more frequently and outpatient dermatologic offices less frequently for their skin conditions. Language barriers, less familiarity with the healthcare system, and lack of adequate health insurance may play roles in this observation.

"I'm Off My Meds": Public Perception of Interactions Between SARS-CoV-2 Vaccines and Anti-Psoriatic Treatments Online.

IMPORTANCE: Psoriasis patients may seek information about the SARS-CoV-2 vaccine and their diagnosis from social media platforms. Analyses of social media interactions may help guide dermatologists’ educational efforts during this pandemic. OBJECTIVES: This study analyzed the content and sentiment of online social media posts about the medication interaction between SARS-CoV-2 vaccines and anti-psoriatic therapies among psoriasis patients. DESIGN: Publicly accessible Facebook and Reddit groups regarding psoriasis and psoriatic arthritis were identified. Posts uploaded between March 1, 2021, and July 31, 2021, with information about the SARS-CoV-2 vaccine and psoriasis and psoriatic arthritis, were extracted. Themes, sentiment scores, and engagement scores were assigned to each post. RESULTS: 477 posts contained content pertaining to the vaccine and psoriatic medications. 19 (4%) of the posts contain negative sentiment, 232 (48.6%) contain neutral sentiment, and 226 (47.4%) contain positive sentiment. Several themes emerged from this study. A majority of posts (32.5%) contained concerns about holding or stopping medications prior to obtaining the vaccine. Other common concerns included fear of negative reaction (21.8%) and uncertainty about the ability to generate an efficient immune response to the vaccine while on anti-psoriatic medications (19.9%). CONCLUSIONS AND RELEVANCE: Concerns identified by our content analysis should be incorporated into education efforts to address the reasons for vaccine hesitancy among patients with psoriatic diseases. These patient concerns can also help guide our strategy for implementing evidence-based recommendations on COVID-19 vaccination. J Drugs Dermatol. 2022;21(8):901-905. doi:10.36849/JDD.6853.

International Dermatology Outcome Measures (IDEOM): Report from the 2021 Annual Meeting.

BACKGROUND: International Dermatology Outcome Measures (IDEOM) is a non-profit organization founded in 2013. It is composed of researchers and stakeholders who work to develop evidenced-based outcome measures to enhance research and treatment recommendations of dermatologic diseases. SUMMARY: The 2021 IDEOM Virtual Annual Meeting occurred from November 19-20, 2021. Contributions were made by leaders and stakeholders from the psoriasis, psoriatic arthritis, pediatric hidradenitis suppurativa, acne, vitiligo, actinic keratosis, alopecia areata, itch, and cutaneous lymphoma workgroups. The psoriasis, psoriatic arthritis, and actinic keratosis workgroups provided an overview of their respective instruments for treatment satisfaction and symptom measurement. The inaugural meetings of the itch, alopecia areata, and cutaneous lymphoma workgroups identified unmet needs of their respective diseases and future goals. The acne, vitiligo, and pediatric hidradenitis suppurativa workgroups discussed concerns of quality of life, instruments for symptom measurement, and screening tools. Additionally, a representative from the US Food and Drug Administration was in attendance and presented an update on topical drugs and generics. This report provides a summary of workgroup updates from the past year and future directions established during the meeting. KEY MESSAGES: This report summarizes progress made by each IDEOM workgroup at the 2021 IDEOM Virtual Annual Meeting. J Drugs Dermatol. 2022;21(8):867-874. doi:10.36849/JDD.6974.

Biologics to breast milk: A cross-sectional study of popular eczema treatment content on TikTok.

We conducted a cross-sectional study to compare viewer engagement, content quality and viewer experience of eczema related medical content on TikTok between health care professionals and non-health care professionals. Compared to non-health care professionals, health care professionals created videos of higher quality and superior viewing experience. Viewer engagement did not differ significantly between videos made by health care professionals and non-health care professionals. Overall, content creators should focus on producing comprehensive, evidence-based videos.

"An Uncommon Complication of Dengue".

Intracranial hemorrhage is an uncommon complication of dengue fever, which is caused by a flavivirus and transmitted via Aedes mosquito. We present here bilateral cerebellar bleed because of dengue virus infection.

A transposase strategy for creating libraries of circularly permuted proteins.

A simple approach for creating libraries of circularly permuted proteins is described that is called PERMutation Using Transposase Engineering (PERMUTE). In PERMUTE, the transposase MuA is used to randomly insert a minitransposon that can function as a protein expression vector into a plasmid that contains the open reading frame (ORF) being permuted. A library of vectors that express different permuted variants of the ORF-encoded protein is created by: (i) using bacteria to select for target vectors that acquire an integrated minitransposon; (ii) excising the ensemble of ORFs that contain an integrated minitransposon from the selected vectors; and (iii) circularizing the ensemble of ORFs containing integrated minitransposons using intramolecular ligation. Construction of a Thermotoga neapolitana adenylate kinase (AK) library using PERMUTE revealed that this approach produces vectors that express circularly permuted proteins with distinct sequence diversity from existing methods. In addition, selection of this library for variants that complement the growth of Escherichia coli with a temperature-sensitive AK identified functional proteins with novel architectures, suggesting that PERMUTE will be useful for the directed evolution of proteins with new functions.

Multi-organ Dysfunction Syndrome with Dual Organophosphate Pesticides Poisoning.

Organophosphate (OP) pesticide self-poisoning is common in developing countries. Poisoning with dual OP compounds is rare. Multi-organ dysfunction after OP poisoning has a high mortality rate. We report the case of a 27-year-old man who developed multi-organ dysfunction syndrome with fatal outcome after intentional ingestion of 50:50 mixture of two OP compounds, dichlorvos and profenofos.

Composite Assembling of Oxide-Based Optically Transparent Electrodes for High-Performance Asymmetric Supercapacitors.

Simultaneously achieving a transparent and high-energy density supercapacitor is a major challenge because of the trade-off between energy storage capacity and optical transparency of active electrode materials. Herein, we demonstrate a novel approach to construct an optically transparent asymmetric supercapacitor (Trans-ASC) by assembling positive (ZnO-SnO2) and negative (TiO2-SnO2) composite thin-film electrodes on a conductive indium-doped tin oxide substrate via reactive DC magnetron cosputtering. The optical transmittance for both composite thin films is found to be 68% (ZnO-SnO2) and 64% (TiO2-SnO2). Furthermore, electrochemical kinematics of the primed transparent electrodes are scrutinized in 0.5 M KOH electrolyte without affecting the transparency of active electrodes. The structural reliability of the electrodes aids the superb electrochemical performance to construct a Trans-ASC, TiO2-SnO2//ZnO-SnO2, which works at a voltage of +1.2 V and attains a higher areal capacitance of 44.6 mF cm-2 at 2 mA cm-2. The assembled Trans-ASC delivers a maximum areal energy density of 8.75 µW h cm-2 with an optimal areal power density of 570 µW cm-2. Additionally, the capacitance retention of 81.6% and transparency of both electrodes remain almost the same (up to 60% for ZnO-SnO2 and 62% for TiO2-SnO2) even after 10,000 charging-discharging cycles. These remarkable electrochemical properties and outstanding cycling stability of the designed Trans-ASC device make it a potential candidate for storing energy and for further use in transparent electronic devices.

Public Perception of SARS-CoV-2 Vaccines Among Psoriasis Patients in Social Media: Content, Sentiment, and Engagement Analysis.

Background: Psoriasis patients may seek information about the SARS-CoV-2 vaccine and their disease from social media platforms. Analyses of social media interactions may help guide dermatologists' educational efforts during this pandemic. Objectives: This study analyzes social media interactions among patients with psoriasis and psoriatic arthritis regarding the SARS-CoV-2 vaccine to determine the misinformation circulating and the apprehension to receiving the vaccine. Methods: Publicly accessible Facebook and Reddit groups regarding psoriasis and psoriatic arthritis were identified. Posts uploaded between March 1, 2021 and July 31, 2021 which contained information about the SARS-CoV-2 vaccine were extracted. First-order themes, sub-themes, sentiment scores and engagement scores were assigned to each post. Results: 345 posts within the first-order theme of vaccination decision and 1379 posts within the first-order theme of vaccine reaction were analyzed. Within vaccination decision, common sub-themes for refusing the vaccine include fear of psoriasis flare up, vaccine is experimental, vaccine is unnecessary, vaccine is dangerous, and concern for reaction/vaccine efficacy while on psoriasis medications. 41.4% of posts contained positive sentiment; whereas, 38.3% contained negative sentiment. Within vaccine reaction, common sub-themes identified were no change to psoriasis, skin/joint flare up, skin flare up attributed specifically to stopping psoriasis medications, skin/joint improvement, and skin flare up but vaccine was worth it. 77.8% of posts contained positive sentiment; whereas, 6.2% contained negative sentiment. Conclusions: Our study identified common SARS-CoV-2 vaccine concerns within the psoriasis community which should be used to guide educational efforts.

Male Infertility Websites: What are Our Patients Reading?

INTRODUCTION: People of reproductive age (20-45 years) turn to the Internet for health information more often than do adults older than the age of 45. We sought to assess the readability and quality of male infertility websites. METHODS: After querying Google for "male infertility," 4 reviewers classified and analyzed the top 60 results. Website information quality was evaluated using the Health on the Net code (HONcode) accreditation status, the Journal of the American Medical Association (JAMA) benchmark criteria, and DISCERN score. We assessed readability using Flesch Reading Ease and Dale-Chall indexes. RESULTS: The DISCERN score average was 44±12 (out of a maximum of 80). A total of 60% (36/60) of websites scored a 1, 2 or 3 ("poor quality"). JAMA criteria were met by 4/60 (6.7%) websites. The mean Dale-Chall score was 9.53±1.30 and the mean Flesch Reading Ease index was 34.01±16.26. Of the websites 20% (12/60) were HONcode certified. CONCLUSIONS: Only 6.7% of male infertility websites satisfied JAMA benchmark criteria. Treatment information was nominal, with only 5% describing risks and 25% discussing benefits. Less than 30% of websites encouraged shared decision making despite requiring a college to graduate degree reading level. However, 72% provided unbiased information, and a majority of websites were hospital based. Providers should caution patients that potentially unreadable and incomplete information on male infertility is prevalent online.

Psoriasis Prevalence in Adults in the United States.

IMPORTANCE: Determining psoriasis prevalence is fundamental to understanding the burden of the disease, the populations most affected, and health policies to address the disease. OBJECTIVE: (1) To determine the prevalence of psoriasis among adults in the US and (2) to evaluate the change in psoriasis prevalence over time since the 2003-2004 National Health and Nutrition Examination Survey (NHANES) data. DESIGN, SETTING, AND PARTICIPANTS: This population-based cross-sectional study used 2011-2014 NHANES data (collected from January 1, 2011, to December 31, 2014) with sampling from a general, noninstitutionalized US civilian population. Participants were 20 years or older and were selected via a multistage probability sampling design to ensure that surveys were nationally representative. Eligible participants had an in-person interview followed by a medical examination by medical professionals. Data were analyzed from July 15, 2019, to December 23, 2020. EXPOSURES: None. MAIN OUTCOMES AND MEASURES: Psoriasis prevalence in the US, as measured by the percentage of people in the representative sample with psoriasis, and trend statistics comparing prevalence estimates from the 2003-2004, 2009-2010, and 2011-2014 NHANES cycles. RESULTS: A total of 12 625 participants (mean [SD] age, 32.8 [24.1] years; 6492 women [51.4%]; and 4828 non-Hispanic White participants [38.2%]) answered the question of whether they were given the diagnosis of psoriasis by a physician or another health care professional. Psoriasis prevalence among US adults 20 years or older was 3.0% (95% CI, 2.6%-3.4%). Based on the 2020 US census data, this outcome translates to an estimated 7.55 million US adults with psoriasis. Psoriasis prevalence was similar between women and men, with 3.2% (95% CI, 2.6%-3.8%) in women and 2.8% (95% CI, 2.4%-3.3%) in men. Psoriasis prevalence was highest in White individuals at 3.6% (95% CI, 2.9%-4.2%), followed by other racial/ethnic groups (non-Hispanic, including multiracial) at 3.1% (95% CI, 1.2%-5.1%), Asian individuals at 2.5% (95% CI, 1.6%-3.3%), Hispanic individuals (including Mexican American and other Hispanic individuals) at 1.9% (95% CI, 1.3%-2.5%), and Black individuals at 1.5% (95% CI, 1.0%-2.0%). Psoriasis prevalence was not different based on patients' marital status, education, income, or medical insurance status. The prevalence of psoriasis among US adults did not differ significantly since 2003. CONCLUSIONS AND RELEVANCE: The results of this cross-sectional study suggest that psoriasis remains a common, immune-mediated disease that affects 3.0% of the US adult population, or more than 7.5 million adults. Its prevalence has not differed since evaluation in 2003. These prevalence data are foundational to determining the burden of psoriasis and for supporting efforts in research, education, and health policy.

Phase-incoherent superconducting pairs in the normal state of Ba(Fe(1-x)Co(x))2As2.

The normal state properties of the recently discovered ferropnictide superconductors might hold the key to understanding their exotic superconductivity. Using point-contact spectroscopy we show that Andreev reflection between an epitaxial thin film of Ba(Fe(0.92)Co(0.08))2As2 and a silver tip can be seen in the normal state of the film up to temperature T∼1.3T(c), where T(c) is the critical temperature of the superconductor. Andreev reflection far above T(c) can be understood only when superconducting pairs arising from strong fluctuation of the phase of the complex superconducting order parameter exist in the normal state. Our results provide spectroscopic evidence of phase-incoherent superconducting pairs in the normal state of the ferropnictide superconductors.

The Multiple Cranial Nerve Palsies: A Prospective Observational Study.

BACKGROUND: Neurological presentation with isolated multiple cranial nerve palsies is common and its diverse causes include infectious, neoplastic, and inflammatory pathologies. The aetiological spectrum may depend upon geographical regions. We undertook this study to explore clinical spectrum and aetiological profile of multiple cranial nerve palsies. METHODS: This hospital-based prospective observational study was conducted from August 2015 to August 2017. All the consecutive patients of multiple cranial palsies presenting to the neurology department were included in the studies. Primary objectives were to define anatomical syndromes/cranial nerve combinations and to establish aetiology. Secondary objectives were to study associated factors. The multiple cranial nerve palsy was defined as involvement of two or more non-homologous nerves. Patients of neuromuscular junction disorders, anterior horn cell disorders, myopathies, brain stem syndromes were excluded. All patients underwent structured protocol of clinical evaluation, investigations and few specialized investigations in accordance with clinical suspicion to establish the diagnosis. RESULTS: Fifty-four patients with a mean age of 39.9 ± 14.2 years were included. Commonest cranial nerve involved was the abducens (75.9%) among all nerve combinations. The cavernous sinus syndrome (37%), orbital apex syndrome (22.2%) and jugular foramen syndrome (11.1%) were the most frequent anatomical patterns. Infections (40.7%) were the commonest aetiology followed by neoplastic and idiopathic in four patients. CONCLUSION: Cavernous sinus syndrome was the commonest anatomical syndrome of multiple cranial nerve palsies and infections were the commonest cause in this study.