The Alopecia Areata Severity and Morbidity Index (ASAMI) Study: Results From a Global Expert Consensus Exercise on Determinants of Alopecia Areata Severity.

Importance: Current measures of alopecia areata (AA) severity, such as the Severity of Alopecia Tool score, do not adequately capture overall disease impact. Objective: To explore factors associated with AA severity beyond scalp hair loss, and to support the development of the Alopecia Areata Severity and Morbidity Index (ASAMI). Evidence Review: A total of 74 hair and scalp disorder specialists from multiple continents were invited to participate in an eDelphi project consisting of 3 survey rounds. The first 2 sessions took place via a text-based web application following the Delphi study design. The final round took place virtually among participants via video conferencing software on April 30, 2022. Findings: Of all invited experts, 64 completed the first survey round (global representation: Africa [4.7%], Asia [9.4%], Australia [14.1%], Europe [43.8%], North America [23.4%], and South America [4.7%]; health care setting: public [20.3%], private [28.1%], and both [51.6%]). A total of 58 specialists completed the second round, and 42 participated in the final video conference meeting. Overall, consensus was achieved in 96 of 107 questions. Several factors, independent of the Severity of Alopecia Tool score, were identified as potentially worsening AA severity outcomes. These factors included a disease duration of 12 months or more, 3 or more relapses, inadequate response to topical or systemic treatments, rapid disease progression, difficulty in cosmetically concealing hair loss, facial hair involvement (eyebrows, eyelashes, and/or beard), nail involvement, impaired quality of life, and a history of anxiety, depression, or suicidal ideation due to or exacerbated by AA. Consensus was reached that the Alopecia Areata Investigator Global Assessment scale adequately classified the severity of scalp hair loss. Conclusions and Relevance: This eDelphi survey study, with consensus among global experts, identified various determinants of AA severity, encompassing not only scalp hair loss but also other outcomes. These findings are expected to facilitate the development of a multicomponent severity tool that endeavors to competently measure disease impact. The findings are also anticipated to aid in identifying candidates for current and emerging systemic treatments. Future research must incorporate the perspectives of patients and the public to assign weight to the domains recognized in this project as associated with AA severity.

Synaptic architecture of leg and wing motor control networks in Drosophila.

Animal movement is controlled by motor neurons (MNs), which project out of the central nervous system to activate muscles. Because individual muscles may be used in many different behaviors, MN activity must be flexibly coordinated by dedicated premotor circuitry, the organization of which remains largely unknown. Here, we use comprehensive reconstruction of neuron anatomy and synaptic connectivity from volumetric electron microscopy (i.e., connectomics) to analyze the wiring logic of motor circuits controlling the Drosophila leg and wing. We find that both leg and wing premotor networks are organized into modules that link MNs innervating muscles with related functions. However, the connectivity patterns within leg and wing motor modules are distinct. Leg premotor neurons exhibit proportional gradients of synaptic input onto MNs within each module, revealing a novel circuit basis for hierarchical MN recruitment. In comparison, wing premotor neurons lack proportional synaptic connectivity, which may allow muscles to be recruited in different combinations or with different relative timing. By comparing the architecture of distinct limb motor control systems within the same animal, we identify common principles of premotor network organization and specializations that reflect the unique biomechanical constraints and evolutionary origins of leg and wing motor control.

Australian dermatologists' prescribing behaviours for male androgenetic alopecia.

Androgenetic alopecia (AGA) is highly prevalent among Australian men and can have significant psychological impacts. Despite its prevalence, treatment options have traditionally been limited. In this study, we examined the current prescribing patterns of Australian dermatologists for male AGA.

Cell-type specific transcriptomic signatures of neocortical circuit organization and their relevance to autism.

A prevailing challenge in neuroscience is understanding how diverse neuronal cell types select their synaptic partners to form circuits. In the neocortex, major classes of excitatory projection neurons and inhibitory interneurons are conserved across functionally distinct regions. There is evidence these classes form canonical circuit motifs that depend primarily on their identity; however, regional cues likely also influence their choice of synaptic partners. We mined the Allen Institute's single-cell RNA-sequencing database of mouse cortical neurons to study the expression of genes necessary for synaptic connectivity and physiology in two regions: the anterior lateral motor cortex (ALM) and the primary visual cortex (VISp). We used the Allen's metadata to parse cells by clusters representing major excitatory and inhibitory classes that are common to both ALM and VISp. We then performed two types of pairwise differential gene expression analysis: (1) between different neuronal classes within the same brain region (ALM or VISp), and (2) between the same neuronal class in ALM and VISp. We filtered our results for differentially expressed genes related to circuit connectivity and developed a novel bioinformatic approach to determine the sets uniquely enriched in each neuronal class in ALM, VISp, or both. This analysis provides an organized set of genes that may regulate synaptic connectivity and physiology in a cell-type-specific manner. Furthermore, it identifies candidate mechanisms for circuit organization that are conserved across functionally distinct cortical regions or that are region dependent. Finally, we used the SFARI Human Gene Module to identify genes from this analysis that are related to risk for autism spectrum disorder (ASD). Our analysis provides clear molecular targets for future studies to understand neocortical circuit organization and abnormalities that underlie autistic phenotypes.

Effective treatment of refractory lichen planus pemphigoides with a Janus kinase-1/2 inhibitor.

Lichen planus pemphigoides is a rare autoimmune subepidermal blistering disease clinically and histopathologically characterized by features of lichen planus and bullous pemphigoid. We describe a case of refractory lichen planus pemphigoides successfully treated with the selective and reversible Janus kinase-1/2 inhibitor, baricitinib.

Biomarkers for the Early Diagnosis of Sepsis in Burns: Systematic Review and Meta-analysis.

OBJECTIVE: The aim of this study was to evaluate the diagnostic performance of all biomarkers studied to date for the early diagnosis of sepsis in hospitalized patients with burns. BACKGROUND: Early clinical diagnosis of sepsis in burns patients is notoriously difficult due to the hypermetabolic nature of thermal injury. A considerable variety of biomarkers have been proposed as potentially useful adjuncts to assist with making a timely and accurate diagnosis. METHODS: We searched Medline, Embase, Cochrane CENTRAL, Biosis Previews, Web of Science, and Medline In-Process to February 2020. We included diagnostic studies involving burns patients that assessed biomarkers against a reference sepsis definition of positive blood cultures or a combination of microbiologically proven infection with systemic inflammation and/or organ dysfunction. Pooled measures of diagnostic accuracy were derived for each biomarker using bivariate random-effects meta-analysis. RESULTS: We included 28 studies evaluating 57 different biomarkers and incorporating 1517 participants. Procalcitonin was moderately sensitive (73%) and specific (75%) for sepsis in patients with burns. C-reactive protein was highly sensitive (86%) but poorly specific (54%). White blood cell count had poor sensitivity (47%) and moderate specificity (65%). All other biomarkers had insufficient studies to include in a meta-analysis, however brain natriuretic peptide, stroke volume index, tumor necrosis factor (TNF)-alpha, and cell-free DNA (on day 14 post-injury) showed the most promise in single studies. There was moderate to significant heterogeneity reflecting different study populations, sepsis definitions and test thresholds. CONCLUSIONS: The most widely studied biomarkers are poorly predictive for sepsis in burns patients. Brain natriuretic peptide, stroke volume index, TNF-alpha, and cell-free DNA showed promise in single studies and should be further evaluated. A standardized approach to the evaluation of diagnostic markers (including time of sampling, cut-offs, and outcomes) would be useful.