Establishing Riboglow-FLIM to visualize noncoding RNAs inside live zebrafish embryos.

The central role of RNAs in health and disease calls for robust tools to visualize RNAs in living systems through fluorescence microscopy. Live zebrafish embryos are a popular system to investigate multicellular complexity as disease models. However, RNA visualization approaches in whole organisms are notably underdeveloped. Here, we establish our RNA tagging and imaging platform Riboglow-FLIM for complex cellular imaging applications by systematically evaluating FLIM capabilities. We use adherent mammalian cells as models for RNA visualization. Additional complexity of analyzing RNAs in whole mammalian animals is achieved by injecting these cells into a zebrafish embryo system for cell-by-cell analysis in this model of multicellularity. We first evaluate all variable elements of Riboglow-FLIM quantitatively before assessing optimal use in whole animals. In this way, we demonstrate that a model noncoding RNA can be detected robustly and quantitatively inside live zebrafish embryos using a far-red Cy5-based variant of the Riboglow platform. We can clearly resolve cell-to-cell heterogeneity of different RNA populations by this methodology, promising applicability in diverse fields.

Underlying intracranial atherosclerotic disease is associated with worse outcomes in acute large vessel occlusion undergoing endovascular thrombectomy.

BACKGROUND: Data on large vessel occlusion (LVO) management due to intracranial atherosclerotic disease (ICAD) are scarce. OBJECTIVE: To compare clinical outcomes between patients with ICAD and those without ICAD following mechanical thrombectomy (MT). METHODS: We performed a retrospective analysis of consecutive patients who underwent MT for LVO in a large academic comprehensive stroke center, and compared in-hospital mortality, 90-day mortality, favorable functional outcome at 90 days, and symptomatic intracranial hemorrhage (ICH) using chi-squared tests and multivariate logistic regression analyses. We defined ICAD as observable plaque at occlusion site post-thrombectomy. RESULTS: Among 215 patients (mean age 67.1 ± 16.0 years; 60.5% female; 83.6% Black, median NIHSS score 16), ICAD was present in 38 patients (17.7%). Diabetes and dyslipidemia were more common in those with ICAD (57.9% vs. 38.4%, p = 0.027 and 29.0% vs. 14.7%, p = 0.035, respectively). Substantial reperfusion (TICI ≥2b) was achieved less often (84.2% vs. 94.4%, p = 0.031) but symptomatic ICH was also less common in ICAD patients (0% vs. 9.0%, p = 0.081). In-hospital and 90-day mortality were more common (36.8% vs. 15.8%, p = 0.003 and 52.6% vs. 26.6%, p = 0.002, respectively) and favorable functional outcome (mRS 0-2) at 90 days was less common (7.9% vs. 33.9%, p = 0.001) in ICAD patients. After adjusting for prognostic variables, ICAD was independently associated with in-hospital mortality (OR=4.1, 95% CI 1.7-9.7), 90-day mortality (OR=3.7, 95% CI 1.6-8.6), and poor functional outcome at 90 days (OR=5.5, 95% CI 1.6-19.4). CONCLUSION: Symptomatic ICAD in a predominantly African American cohort is associated with increased odds of mortality and poor functional outcome at 90 days in patients with LVO undergoing MT.

Psilocybin's Potential Mechanisms in the Treatment of Depression: A Systematic Review.

Evidence suggests that psilocybin has therapeutic benefit for treating depression. However, there is little consensus regarding the mechanism by which psilocybin elicits antidepressant effects. This systematic review summarizes existing evidence. Ovid MEDLINE, EMBASE, psychINFO, and Web of Science were searched, for both human and animal studies, using a combination of MeSH Terms and free-text keywords in September 2021. No other mood disorders or psychiatric diagnoses were included. Original papers in English were included. The PRISMA framework was followed for the screening of papers. Two researchers screened the retrieved articles from the literature search, and a third researcher resolved any conflicts. Of 2,193 papers identified, 49 were selected for full-text review. 14 articles were included in the qualitative synthesis. Six supported psilocybin's mechanism of antidepressant action via changes to serotonin or glutamate receptor activity and three papers found an increase in synaptogenesis. Thirteen papers investigated changes in non-receptor or pathway-specific brain activity. Five papers found changes in functional connectivity or neurotransmission, most commonly in the hippocampus or prefrontal cortex. Several neuroreceptors, neurotransmitters, and brain areas are thought to be involved in psilocybin's ability to mitigate depressive symptoms. Psilocybin appears to alter cerebral blood flow to the amygdala and prefrontal cortex, but the evidence on changes in functional connectivity and specific receptor activity remains sparse. The lack of consensus between studies suggests that psilocybin's mechanism of action may involve a variety of pathways, demonstrating the need for more studies on psilocybin's mechanism of action as an antidepressant.

Twisted Carotenoids Do Not Support Efficient Intramolecular Singlet Fission in the Orange Carotenoid Protein.

Singlet exciton fission is the spin-allowed generation of two triplet electronic excited states from a singlet state. Intramolecular singlet fission has been suggested to occur on individual carotenoid molecules within protein complexes provided that the conjugated backbone is twisted out of plane. However, this hypothesis has been forwarded only in protein complexes containing multiple carotenoids and bacteriochlorophylls in close contact. To test the hypothesis on twisted carotenoids in a "minimal" one-carotenoid system, we study the orange carotenoid protein (OCP). OCP exists in two forms: in its orange form (OCPo), the single bound carotenoid is twisted, whereas in its red form (OCPr), the carotenoid is planar. To enable room-temperature spectroscopy on canthaxanthin-binding OCPo and OCPr without laser-induced photoconversion, we trap them in a trehalose glass. Using transient absorption spectroscopy, we show that there is no evidence of long-lived triplet generation through intramolecular singlet fission despite the canthaxanthin twist in OCPo.

Understanding the Molecular Basis for Homodimer Formation of the Pneumococcal Endolysin Cpl-1.

The rise of multi-drug-resistant bacteria that cannot be treated with traditional antibiotics has prompted the search for alternatives to combat bacterial infections. Endolysins, which are bacteriophage-derived peptidoglycan hydrolases, are attractive tools in this fight. Several studies have already demonstrated the efficacy of endolysins in targeting bacterial infections. Endolysins encoded by bacteriophages that infect Gram-positive bacteria typically possess an N-terminal catalytic domain and a C-terminal cell-wall binding domain (CWBD). In this study, we have uncovered the molecular mechanisms that underlie formation of a homodimer of Cpl-1, an endolysin that targets Streptococcus pneumoniae. Here, we use site-directed mutagenesis, analytical size exclusion chromatography, and analytical ultracentrifugation to disprove a previous suggestion that three residues at the N-terminus of the CWBD are involved in the formation of a Cpl-1 dimer in the presence of choline in solution. We conclusively show that the C-terminal tail region of Cpl-1 is involved in formation of the dimer. Alanine scanning mutagenesis generated various tail mutant constructs that allowed identification of key residues that mediate Cpl-1 dimer formation. Finally, our results allowed identification of a consensus sequence (FxxEPDGLIT) required for choline-dependent dimer formation─a sequence that occurs frequently in pneumococcal autolysins and endolysins. These findings shed light on the mechanisms of Cpl-1 and related enzymes and can be used to inform future engineering efforts for their therapeutic development against S. pneumoniae.

Visualizing orthogonal RNAs simultaneously in live mammalian cells by fluorescence lifetime imaging microscopy (FLIM).

Visualization of RNAs in live cells is critical to understand biology of RNA dynamics and function in the complex cellular environment. Detection of RNAs with a fluorescent marker frequently involves genetically fusing an RNA aptamer tag to the RNA of interest, which binds to small molecules that are added to live cells and have fluorescent properties. Engineering efforts aim to improve performance and add versatile features. Current efforts focus on adding multiplexing capabilities to tag and visualize multiple RNAs simultaneously in the same cell. Here, we present the fluorescence lifetime-based platform Riboglow-FLIM. Our system requires a smaller tag and has superior cell contrast when compared with intensity-based detection. Because our RNA tags are derived from a large bacterial riboswitch sequence family, the riboswitch variants add versatility for using multiple tags simultaneously. Indeed, we demonstrate visualization of two RNAs simultaneously with orthogonal lifetime-based tags.

MALT1 regulates Th2 and Th17 differentiation via NF-κB and JNK pathways, as well as correlates with disease activity and treatment outcome in rheumatoid arthritis.

Objective: MALT1 regulates immunity and inflammation in multiple ways, while its role in rheumatoid arthritis (RA) is obscure. This study aimed to investigate the relationship of MALT1 with disease features, treatment outcome, as well as its effect on Th1/2/17 cell differentiation and underlying molecule mechanism in RA. Methods: Totally 147 RA patients were enrolled. Then their blood Th1, Th2, and Th17 cells were detected by flow cytometry. Besides, PBMC MALT1 expression was detected before treatment (baseline), at week (W) 6, W12, and W24. PBMC MALT1 in 30 osteoarthritis patients and 30 health controls were also detected. Then, blood CD4+ T cells were isolated from RA patients, followed by MALT1 overexpression or knockdown lentivirus transfection and Th1/2/17 polarization assay. In addition, IMD 0354 (NF-κB antagonist) and SP600125 (JNK antagonist) were also added to treat CD4+ T cells. Results: MALT1 was increased in RA patients compared to osteoarthritis patients and healthy controls. Meanwhile, MALT1 positively related to CRP, ESR, DAS28 score, Th17 cells, negatively linked with Th2 cells, but did not link with other features or Th1 cells in RA patients. Notably, MALT1 decreased longitudinally during treatment, whose decrement correlated with RA treatment outcome (treatment response, low disease activity, or disease remission). In addition, MALT1 overexpression promoted Th17 differentiation, inhibited Th2 differentiation, less affected Th1 differentiation, activated NF-κB and JNK pathways in RA CD4+ T cells; while MALT1 knockdown exhibited the opposite effect. Besides, IMD 0354 and SP600125 addition attenuated MALT1's effect on Th2 and Th17 differentiation. Conclusion: MALT1 regulates Th2 and Th17 differentiation via NF-κB and JNK pathways, as well as correlates with disease activity and treatment outcome in RA.

Benevolent Sexism and the Traditional Sexual Script as Predictors of Sexual Dissatisfaction in Heterosexual Women from the U.S.

Women report lower sexual satisfaction than men. Given that sexual dissatisfaction adversely impacts health and well-being, it is imperative that we investigate why women are sexually dissatisfied. In the present study, we explored whether women's benevolently sexist attitudes might predict their sexual dissatisfaction. In a sample of 308 (Mage = 38.09) heterosexual American women who had previously had sex with a man, we hypothesized that women's benevolent sexism would be associated with an increased adoption of the traditional sexual script (i.e., an increased propensity for submissiveness and passivity during sex) and that this, in turn, would be associated with increased sexual dissatisfaction. We also hypothesized that the relationship between the adoption of the traditional sexual script and sexual dissatisfaction would be moderated by the degree to which participants enjoy submissiveness. Overall, we did not find support for our model: benevolent sexism did not predict sexual dissatisfaction. However, we did find that adopting the traditional sexual script was predictive of sexual dissatisfaction for women who do not enjoy submissiveness. These findings contribute to an emerging literature pertaining to women's sexual health. Specifically, results suggest that benevolent sexism does not contribute to women's experiences of sexual dissatisfaction. Instead, they suggest that sexual dissatisfaction in women may (in part) be driven by their engagement in sexual roles that do not align with their sexual preferences. Theoretical and clinical implications for these findings are discussed.

Jaw Reduction Surgery.

Facial feminization surgery (FFS) combines a series of facial bone and soft tissue surgeries to feminize the masculine appearance of the face in a transgender female patient. Jaw reduction surgery is an extremely critical component of FFS and is generally performed in combination with genioplasty. Our technique of jaw reduction involves sagittal resection of the mandible from the angle of the jaw to the mental nerve region. This creates a smooth transition from the ramus to the chin and also retains the integrity of the inner portion of the mandible. We discuss our techniques of jaw reduction surgery in this article.

Longitudinal changes in age and race of patients with SARS-CoV-2 in a multi-hospital health system

BackgroundThe COVID-19 pandemic continues to affect the United States and the world. Media reports have suggested that the wave of the alpha variant in the Spring of 2021 in the US caused more cases among younger patients and racial and ethnic subgroups. ApproachWe analyzed electronic health record data from a multihospital health system to test whether younger patients accounted for more cases and more severe disease, and whether racial disparities are widening. We compared demographics, patient characteristics, and hospitalization variables for patients admitted from November 2020 through January 2021 to those admitted in March and April 2021. ResultsWe analyzed data for 37, 502 unique inpatients and outpatients at 21 hospitals from November 1, 2020 to April 30, 2021. Compared to patients from November through January, those with positive tests in March and April were younger and less likely to die. Among patients under age 50, those with positive tests in March and April were three times as likely to be hospitalized and twice as likely to require ICU admission or mechanical ventilation. Individuals identified as Black represented a greater proportion of cases and hospitalizations in March and April as compared to November through January. ConclusionsWe found that relative COVID-19 hospitalization rates for younger individuals and individuals identified as Black were rising over time. These findings have important implications for ongoing public health measures to mitigate the impact of the pandemic.

Selective cysteine-to-selenocysteine changes in a [NiFe]-hydrogenase confirm a special position for catalysis and oxygen tolerance.

In [NiFe]-hydrogenases, the active-site Ni is coordinated by four cysteine-S ligands (Cys; C), two of which are bridging to the Fe(CO)(CN)2 fragment. Substitution of a single Cys residue by selenocysteine (Sec; U) occurs occasionally in nature. Using a recent method for site-specific Sec incorporation into proteins, each of the four Ni-coordinating cysteine residues in the oxygen-tolerant Escherichia coli [NiFe]-hydrogenase-1 (Hyd-1) has been replaced by U to identify its importance for enzyme function. Steady-state solution activity of each Sec-substituted enzyme (on a per-milligram basis) is lowered, although this may reflect the unquantified presence of recalcitrant inactive/immature/misfolded forms. Protein film electrochemistry, however, reveals detailed kinetic data that are independent of absolute activities. Like native Hyd-1, the variants have low apparent KMH2 values, do not produce H2 at pH 6, and display the same onset overpotential for H2 oxidation. Mechanistically important differences were identified for the C576U variant bearing the equivalent replacement found in native [NiFeSe]-hydrogenases, its extreme O2 tolerance (apparent KMH2 and Vmax [solution] values relative to native Hyd-1 of 0.13 and 0.04, respectively) implying the importance of a selenium atom in the position cis to the site where exogenous ligands (H-, H2, O2) bind. Observation of the same unusual electrocatalytic signature seen earlier for the proton transfer-defective E28Q variant highlights the direct role of the chalcogen atom (S/Se) at position 576 close to E28, with the caveat that Se is less effective than S in facilitating proton transfer away from the Ni during H2 oxidation by this enzyme.

Impact of FDA Updates on Public Interest in Breast Implant-associated Anaplastic Large Cell Lymphoma.

In the United States, the Food and Drug Administration (FDA) is responsible for protecting the public health by assuring the safety, efficacy, and security of drugs, biological products, and medical devices. In that role, FDA releases timely updates with regard to medical devices and their possible adverse effects. However, the impact of such FDA updates on public interest has not been studied. The timing of multiple FDA updates regarding Breast Implant-Associated Anaplastic Large Cell Lymphoma (BIA-ALCL) was noted from September 2014 to September 2019. Impact on Public interest related to ALCL was measured using Google Trends and the number of YouTube video uploads. These objective markers were used to compare the public interest during FDA updates versus weeks with no FDA updates. Five major updates were released by FDA regarding BIA-ALCL during the past 5 years. Google Trends demonstrated a significant increase in public interest regarding ALCL during the week of FDA release, with a mean score of 69 ± 20.82 when compared with a mean score of 10.68 ± 4.71 (P < 0.001) during weeks with no FDA release. The mean number of YouTube videos uploaded during the period of FDA release was 11.8 ± 9.42, which was significantly higher than the mean of 2.42 ± 1.31 videos (P < 0.001) during the period of no FDA updates. FDA updates correlates with temporal increase in public interest. Plastic surgeons should be aware of FDA information releases on BIA-ALCL and anticipate an increased interest in additional information from patients and the public.

Consummatory, Feeding Microstructural, and Metabolic Effects Induced by Limiting Access to Either a High-Sucrose or a High-Fat Diet.

BACKGROUND: Binge eating disorder (BED) is characterized by recurrent binge eating episodes consisting of rapid consumption of excessive amounts of highly palatable, energy-dense food within discrete periods of time. The aim of this study was to test the consummatory, food microstructural, and metabolic effects of a one hour limited access to either a high-sucrose diet (HSD) or a high-fat diet (HFD) in an operant rat model of binge-like eating. METHODS: Female rats were subject to a binge-like eating procedure in which a HSD, a HFD, or a standard chow diet were provided in a fixed ratio 1 (FR1) operant schedule of reinforcement. RESULTS: Limiting access to either a HSD or a HFD promoted binge-like eating as compared to the control chow diet. However, binge-like eating of HSD, but not HFD, was based on a true increase in the amount of food consumed, an increased eating rate, and a decrease in the intake of the home-cage standard chow, altogether suggesting an increase in palatability. Moreover, while HSD rats consumed overall less energy than HFD rats, the former were more energy efficient and gained more body weight than the latter. CONCLUSIONS: These results provide information on how the quality of food can deeply influence the behavioral and metabolic outcomes of binge-like eating.

Predictors of positive bone cultures from CT-guided bone biopsies performed for suspected osteomyelitis.

INTRODUCTION: Bone biopsies are often used to direct antibiotic choice in patients with suspected osteomyelitis. The aim of this study was to identify the best predictors of positive bone biopsy cultures. METHODS: A retrospective review of 845 patients who underwent computed tomography (CT)-guided non-spine bone biopsies at a tertiary academic healthcare institution. Thirty-seven patients (4.4%) had biopsies performed for suspected osteomyelitis. Laboratory markers, as well as imaging features, were measured. t-Tests and Fisher's exact tests were used to compare clinical and demographic variables between patients with positive bone cultures and patients with negative bone cultures. Multivariable logistic regression was used to identify the best predictors of bone culture positivity. RESULTS: All patients had negative blood cultures; however, only eight patients (21.6%) had positive bone cultures, with Staphyloccocus the most common organism. Multivariable logistic regression analysis showed that an open wound (OR = 14.00, 95% CI (1.74, 112.4), p = 0.013) and any fluid aspirated at the time of biopsy (OR = 10.50, 95% CI (1.21, 91.01), p = 0.033) were the best predictors of bone culture positivity. The area under the curve (AUC) for this multivariable model was 0.784 with sensitivity and specificity of 0.778 and 0.778, respectively. Interestingly, and contrary to popular belief, open wounds with exposed bone did not always yield positive bone cultures, and when cultures were positive, were not polymicrobial. CONCLUSIONS: Aspiration of fluid at the time of biopsy and the presence of an open wound are the best predictors of positive bone cultures.

Change in Bone CT Attenuation and C-reactive Protein Are Predictors of Bone Biopsy Culture Positivity in Patients With Vertebral Discitis/Osteomyelitis.

STUDY DESIGN: Case-control study. OBJECTIVE: The objective of this study was to identify the best laboratory and imaging factors to predict bone biopsy culture positivity in the setting of vertebral discitis/osteomyelitis (VDO). SUMMARY OF BACKGROUND DATA: Good predictors of bone biopsy culture positivity in the setting of VDO are unknown. METHODS: Retrospective review was performed for 46 patients who underwent CT-guided bone biopsy for the evaluation of clinically confirmed VDO. Erythrocyte sedimentation rate, C-reactive protein (CRP), mean CT attenuation of the biopsied bone, and the change in the CT attenuation of the bone compared to unaffected vertebral bone (delta CT attenuation) were measured. Receiver-operator characteristic curve analyses were performed to identify the optimal threshold value for each variable. A multivariable logistic regression model was used to predict the probability of a positive bone culture using delta CT attenuation and CRPx100% fold above normal. RESULTS: For one of the 46 VDO patients, bone cultures were not obtained. Approximately 35.6% (16/45) of bone cultures were positive. The most significant predictors of bone culture positivity were CRP x100% fold above normal (P = 0.011) and delta CT attenuation (P = <0.001). Optimized predictive thresholds were calculated to be CRP 4-fold above normal reference value (90.9% sensitivity, 73.7% specificity), or if the CT attenuation of the affected vertebral body was >25.9 HU lower relative to unaffected bone (93.8% sensitivity, 75.0% specificity). CONCLUSION: Delta CT attenuation, as well as CRP level over four times the upper limits of normal, were the strongest predictors for bone culture positivity in patients with VDO. LEVEL OF EVIDENCE: 3.

Placebo responses in randomized controlled trials for systemic therapy in atopic dermatitis: A systematic review and meta-analysis.

BACKGROUND: Atopic dermatitis (AD) has a variable disease course and intermittent triggers, and responses to topical therapy vary, potentially affecting the magnitude of the placebo response in AD trials. OBJECTIVE: To determine the predictors of increased placebo response in randomized controlled trials of AD. METHODS: We performed a systematic review and meta-analysis of randomized controlled trials for systemic therapy in AD published during 2007-2018. We searched the Cochrane Library, Medline, Embase, Global Resource for EczemA Trials (GREAT), Literature of the Latin American and Caribbean Health Sciences (LILACS), and Scopus. Two authors performed study selection and data extraction. Multivariable mixed models were constructed for Cohen D of Eczema Area and Severity Index (EASI), SCORing Atopic Dermatitis (SCORAD), numeric rating scale (NRS)-itch and visual analog scale (VAS)-itch, and Dermatology Life Quality Index (DLQI). RESULTS: Overall, 64 trials were included. Use of concomitant topical therapy prescriptions, study duration ≥3 months, and fewer treatment arms were associated with an increased placebo response for EASI, NRS- and VAS-itch, and DLQI. For EASI, the placebo response was increased in studies with a higher proportion of male patients, mild-moderate mean baseline EASI scores, and no blinding. For NRS-itch, and VRS-itch, higher placebo responses were associated with higher proportions of male patients and moderate-severe mean itch scores at baseline. CONCLUSION: Placebo responses can be reduced in clinical trials of systemic therapy in AD by incorporating double- and triple-blinding, balancing the sex distribution of patients, disallowing concomitant use of prescription topical therapy, and having shorter study durations.

Evaluation of cerebral oxygen perfusion during shoulder arthroplasty performed in the semi-beach chair position.

BACKGROUND: The beach chair position is commonly used when performing shoulder arthroplasty. However, this position has been associated with hypotension, potentially leading to cerebral hypoperfusion, which may cause neurologic injury. In addition, shoulder arthroplasty cases are associated with longer operative times, posing a potentially greater risk of cerebral hypoperfusion. We aim to evaluate the risk of cerebral desaturation events (CDEs) during the course of total shoulder arthroplasty. METHODS: Twenty-six patients undergoing shoulder arthroplasties were monitored for changes in cerebral perfusion. Seven specific time-points during the procedure were labeled for comparison of events: baseline, beach chair, incision, humeral broaching, glenoid reaming, glenoid component implantation, and humeral component implantation. Cerebral oxygen perfusion was measured using near-infrared spectroscopy. A CDE was described as a decrease of oxygen saturation greater than 20%. RESULTS: Nineteeen of 25 subjects experienced a CDE. 42% of these patients experienced CDEs during semi-beach chair positioning. Patients experienced the largest oxygen saturation drop during semi-beach chair positioning. Transition from baseline to semi-beach chair was the only event to have a statistically significant decrease in cerebral perfusion (8%, P < .05). There was a statistically significant percentage change in mean oxygen saturation in the semi-beach chair interval (10%, P < .01) and the semi-beach chair to incision interval (7%, P < .01). CONCLUSIONS: Most patients experienced an intraoperative CDE, with greatest incidence during semi-beach chair positioning. The largest decline in cerebral oxygen saturation occurred during semi-beach chair positioning. Implant implantation was not associated with decrease in cerebral oximetry.

Epidemiology of alopecia areata, ophiasis, totalis, and universalis: A systematic review and meta-analysis.

BACKGROUND: Alopecia areata (AA) is a common autoimmune alopecia with heterogeneous severity and distribution. Previous studies found conflicting results about AA epidemiology. OBJECTIVE: To determine the prevalence, incidence, and predictors of AA, alopecia totalis, alopecia ophiasis, and alopecia universalis. METHODS: A systematic review of all published cohort and cross-sectional studies that analyzed AA and its subtypes. MEDLINE, Embase, LILACS, Scopus, Cochrane Library, and GREAT were searched. At least 2 reviewers performed study title/abstract review and data extraction. Random-effects meta-analysis was used because of significant heterogeneity (I2 = 99.97%). RESULTS: Ninety-four studies met the inclusion criteria. The pooled prevalence (95% confidence interval, N) of AA overall was 2.11% (1.82-2.42, N = 302,157,365), with differences of population-based (0.75% [0.49-1.06%], N = 301,173,403) and clinic-based (3.47% [3.01-3.96], N = 983,962) studies. The prevalences of alopecia totalis, ophiasis, and universalis were 0.08% (0.04-0.13, N = 1,088,149), 0.02% (0.00-0.06, N = 1,075,203), and 0.03% (0.01-0.06, N = 1,085,444), respectively. AA prevalence (95% confidence interval) increased over time (<2000: 1.02% [0.85-1.22]; 2000-2009: 1.76% [1.51-2.03]; >2009: 3.22% [2.59-3.92]; P < .0001) and differed by region. AA prevalence was significantly lower in adults (1.47% [1.18-1.80]) than children (1.92% [1.31-2.65]; P < .0001). CONCLUSIONS: AA affects 2% of the global population. AA prevalence is lower in adults than children, is increasing over time, and significantly differs by region.

Association between hidradenitis suppurativa, depression, anxiety, and suicidality: A systematic review and meta-analysis.

BACKGROUND: Previous studies found conflicting results about whether hidradenitis suppurativa (HS) is associated with depression or anxiety. OBJECTIVES: To determine the relationship of HS with depression and anxiety. METHODS: A systematic review was performed of published observational studies in MEDLINE, PubMed, Embase, Global Resource for Eczema Trials (GREAT), Latin American and Caribbean Health Sciences Literature (LILACS), Cochrane, Scopus, and PsychInfo that analyzed depression or anxiety in HS. Two reviewers performed title/abstract review and data extraction. Meta-analysis was performed with random-effects weighting. RESULTS: Thirty-eight studies met inclusion criteria; 27 had sufficient data for meta-analysis. The prevalences of depression (26.5% vs 6.6%) and anxiety (18.1% vs 7.1%) were higher in persons with versus without HS. Patients with HS had higher odds of depression in 12 of 13 studies and pooled analysis (odds ratio, 2.54; 95% confidence interval, 2.15-3.01), and anxiety in 6 of 6 studies and pooled analysis (odds ratio, 2.00; 95% confidence interval, 1.66-2.42). Similar results were found in sensitivity analyses for different methods of HS diagnosis (physician diagnosed and chart review) and control groups (healthy and dermatologic control individuals). HS was associated with higher antidepressant and anxiolytic use and with suicidality, but not mean depression and anxiety scale scores. LIMITATIONS: Individual-level data were unavailable. CONCLUSIONS: Patients with HS have higher odds of depression, anxiety, and suicidality.