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Abstract The Paneth cell, a secretory cell of the small intestine, expresses numerous host defense proteins, and is hypothesized to play an important role in host defense against infection. However, studying gene expression in this cell requires invasive procedures. To test the hypothesis that we could observe Paneth cell-specific gene regulation from exfoliated cells in infectious conditions, we obtained stool samples from patients with COVID-19 and uninfected controls. Total mRNA was isolated, and Paneth cell-specific and non-specific gene expression was quantified by RT-PCR. Results revealed a significant decrease in mRNA levels from Paneth cell-specific genes, including DEFA5, DEFA6, PLA2G2A, PRSS2 and ITLN2 in SARS-CoV-2 positive patients compared with controls. Other gut markers, not specific to Paneth cells were unchanged. To validate this experimentally, we infected mice with SARS-CoV-2 and collected fecal pellets over the course of 7 days. We observed a similar time-dependent reduction in Paneth cell-specific transcripts, which correlates with histological changes in the gut. This is the first demonstration of quantification of Paneth cell-specific transcripts without invasive sampling. It also shows the coordinate regulation of these genes as a response to infection with SARS-CoV-2, possibly through viral pathogenesis, to increase infectivity in the gut.

The life cycle of most marine invertebrates includes a planktonic larval stage before metamorphosis to bottom-dwelling adulthood. During the larval stage, ciliary-mediated activity enables feeding (capturing unicellular algae) and transporting materials (e.g., oxygen) required for the larva’s growth, development, and successful metamorphosis. Investigating the underlying hydrodynamics of the ciliary activities is valuable for addressing fundamental biological questions (e.g., phenotypic plasticity) and advancing engineering applications (e.g., biomimetic design). We combined microfluidics and fluorescence microscopy as a miniaturized particle image velocimetry approach to study ciliary-mediated hydrodynamics during suspension feeding in sand dollar larvae (Dendraster excentricus). First, feasibility was confirmed by examining the underlying hydrodynamics (ciliary-mediated vortex patterns) for low- and high-fed larvae. Next, ciliary hydrodynamics were tracked from 11 days post-fertilization (DPF) to 20 DPF for 21 low-fed larvae. Microfluidics enabled the examination of baseline activities (without external flow) and behaviors in the presence of environmental cues (external flow). A library of qualitative vortex patterns and quantitative hydrodynamics (velocity and vorticity profiles) was generated. Velocities were used to examine the role of ciliary activity in transporting materials. Given the laminar flow and the viscosity-dominated environments surrounding the larvae, overcoming the diffusive boundary layer is critical. Péclet number analysis for oxygen transport suggested that ciliary velocities help overcome the diffusion-dominated transport. The approach was used to examine the hydrodynamics of two additional marine larvae (P. helianthoides and S. purpuratus). Microfluidics provided a scalable and accessible approach for investigating the ciliary hydrodynamics of marine organisms.

ABSTRACT Recent case reports and epidemiological data suggest that fungal infections represent an underappreciated complication among people with severe COVID-19. However, the frequency of fungal colonization in patients with COVID-19 and associations with specific immune responses in the airways remain incompletely defined. We previously generated a single-cell RNA-sequencing data set characterizing the upper respiratory microenvironment during COVID-19 and mapped the relationship between disease severity and the local behavior of nasal epithelial cells and infiltrating immune cells. Our previous study, in agreement with findings from related human cohorts, demonstrated that a profound deficiency in host immunity, particularly in type I and type III interferon signaling in the upper respiratory tract, is associated with rapid progression to severe disease and worse clinical outcomes. We have now performed further analysis of this cohort and identified a subset of participants with severe COVID-19 and concurrent detection of Candida species-derived transcripts within samples collected from the nasopharynx and trachea. Here, we present the clinical characteristics of these individuals. Using matched single-cell transcriptomic profiles of these individuals’ respiratory mucosa, we identify epithelial immune signatures suggestive of IL17 stimulation and anti-fungal immunity. Further, we observe a significant expression of anti-fungal inflammatory cascades in the nasal and tracheal epithelium of all participants who went on to develop severe COVID-19, even among participants without detectable genetic material from fungal pathogens. Together, our data suggest that IL17 stimulation—in part driven by Candida colonization—and blunted interferon signaling represent a common feature of severe COVID-19 infection.IMPORTANCEIn this paper, we present an analysis suggesting that symptomatic and asymptomatic fungal coinfections can impact patient disease progression during COVID-19 hospitalization. By looking into the presence of other pathogens and their effect on the host immune response during COVID-19 hospitalizations, we aim to offer insight into an underestimated scenario, furthering our current knowledge of determinants of severity that could be considered for future diagnostic and intervention strategies.

As with the broad field of deep learning, autonomy is a research topic that has experienced a heavy explosion in attention from both the scientific and commercial industries due to its potential for the advancement of humanity in many cross-cutting disciplines. Recent advancements in computer vision-based autonomy has highlighted the potential for the realization of increasingly sophisticated autonomous ground vehicles for both commercial and non-traditional applications, such as grocery delivery. Part of the success of these technologies has been a boon in the abundance of training data that is available for training the autonomous behaviors associated with their autonomy software. These data abundance advantage is quickly diminished when an application moves from structured environments, i.e., well-defined city road networks, highways, street signage, etc., into unstructured environments, i.e., cross-country, off-road, non-traditional terrains. Herein, we aim to present insights, from a dataset perspective, into how the scientific community can begin to expand autonomy into unstructured environments, while highlighting some of the key challenges that are presented with such a dynamic and ever-changing environment. Finally, a foundation is laid for the creation of a robust off-road dataset being developed by the Engineer Research and Development Center and Mississippi State University’s Center for Advanced Vehicular Systems.

HemoCue analyzers are standard point-of-care devices for measuring blood hemoglobin concentration ([Hb]). The utility of these photometers has been demonstrated for all vertebrate lineages including birds, yet because most vertebrates except mammals possess nucleated red-blood cells, their [Hb] readings are inflated upward in these taxa and require a correction factor relative to the reference calibration. We field tested the newest of these analyzers, Hb801, against its predecessor, the Hb201+. Because of differences in the photometry methods, these two analyzers were not found to be equivalent for taxa with nucleated red-blood cells, such as birds. Whereas a correction factor of 1.0–1.4 g/dL is required for the Hb201+, it may be that no correction factor is required for the Hb801. Further study of the Hb801 relative to a gold-standard reference in non-mammalian lineages is warranted.

Abstract Background Preliminary evidence shows a possible association between hidradenitis suppurativa (HS) and obstructive sleep apnea (OSA), which is associated with various cardiovascular comorbidities. Objectives To determine the odds of OSA among patients with HS compared with patients without HS. Methods We performed a cross‐sectional analysis using the All of Us research program database using electronic health records (EHR) and survey data from individual patient records extracted on 7 May 2022. Adult patients with available EHR records who either had at least one recorded diagnosis of HS determined by SNOMED‐CT code (HS cohort) or did not have a diagnosis (non‐HS cohort). The main outcome was a diagnosis of OSA as determined by SNOMED‐CT code. Demographic features, survey data, and relevant comorbidities were also collected. Results A total of 1647 patients with HS and 269,492 patients without HS were included. Of the HS patients, the mean age was 50.2 years, 79.0% were female, 39.8% were African American, 38.4% were White, and 17.4% were Hispanic or Latino. The prevalence of OSA in HS patients was 22.2% compared with 4.8% in non‐HS patients. Univariate and multivariate odds ratios of OSA between HS and non‐HS patients were 3.04 (95% confidence interval [CI]: 2.70–3.42) and 2.00 (95% CI: 1.72–2.33), respectively. The odds of OSA were highest in HS patients who were male, white, over 65 years of age, obese, and had hypertension, or hypothyroidism. Conclusions The odds of being affected by both HS and OSA are augmented by multiple demographic factors, including white race, male gender, obesity, hypertension, hypothyroidism, and age over 65. Longitudinal studies are needed to confirm these findings.

Background:. Hidradenitis suppurativa (HS) is an understudied disease, and current HS studies have focused on participants already connected to dermatologic care. Objective:. We surveyed participants in online HS support communities to gain a comprehensive understanding of how provider type impacts HS disease management and the issues individuals with HS face when accessing care. Methods:. From June 13 to June 30, 2021, we administered an anonymous cross-sectional online survey to HS Facebook support group participants who had a self-confirmed diagnosis of HS. Survey items assessed respondent demographics, primary HS provider, and barriers to HS care and pain management. Descriptive analyses are presented. Results:. The survey was viewed 5,168 times and 1,040 surveys met eligibility criteria (20.1%). Survey participants were 97% female and 72% White. Seventy-two percentage resided in the United States and 22% in Europe. Forty-seven percentage reported having a dermatologist as their primary HS provider, 38% reported a nondermatologist, and 15% reported no HS provider. We found that Asian race, full-time employment, private health insurance, and urban setting were each associated with higher rates of having a dermatologist as a primary HS provider. However, 43.7% of those with a dermatologist reported biologic use, as compared with 14.5% with nondermatologist HS providers. Our cohort was notably more severely impacted by comorbid diseases; 55.9% of our cohort had anxiety, 53.6% had depression, and 50.7% had obesity. Overall, 74.2% of our cohort reported experiencing stigma while accessing care for their HS. Limitations:. Participant recruitment via social media platform facilitates recruitment of individuals across the spectrum of healthcare access, but may introduce selection bias and favor well-resourced areas. Self-reported data may be subject to recall bias. Conclusion:. Our study provides unique insights into the characteristics and experiences of individuals with HS across the spectrum of health care access.

One of the earliest neurobiological findings in autism has been the differences in the thalamocortical pathway connectivity, suggesting the vital role thalamus plays in human experience. The present functional MRI study investigated resting-state functional connectivity of the thalamus in 49 (autistic, ADHD, and neurotypical) young adults. All participants underwent structural MRI and eyes-open resting state functional MRI scans. After preprocessing the imaging data using Conn’s connectivity toolbox, a seed-based functional connectivity analysis was conducted using bilateral thalamus as primary seeds. Autistic participants showed stronger thalamic connectivity, relative to ADHD and neurotypical participants, between the right thalamus and right precentral gyrus, right pars opercularis-BA44, right postcentral gyrus, and the right superior parietal lobule (RSPL). Autistic participants also showed significantly increased connectivity between the left thalamus and the right precentral gyrus. Furthermore, regression analyses revealed a significant relationship between autistic traits and left thalamic-precentral connectivity (R2 = 0.1113), as well as between autistic traits and right postcentral gyrus and RSPL connectivity (R2 = 0.1204) in autistic participants compared to ADHD. These findings provide significant insights into the role of thalamus in coordinating neural information processing and its alterations in neurodevelopmental disorders.

Abstract Background Patients with high‐intermediate risk endometrial cancer (H‐IR EMCA) have an elevated risk of recurrence compared to low‐risk counterparts. Many H‐IR EMCA patients are treated with radiation or chemotherapy, but their overall survival is not significantly impacted by treatment. The objective of this study was to compare molecular profiles of H‐IR EMCA patients with disease recurrence to those without to identify characteristics that could better predict patient outcomes. Methods Tissue was acquired from H‐IR EMCA patients with disease recurrence (n=15) and without disease recurrence (n=15) who had not received adjuvant therapy and performed DNA and RNA analyses. Results In recurrent population, 5 patients had matchingrecurrent and initial tumor tissues. Of note, 5/7 (71%) African Americanpatients had disease recurrence compared to 10/23 (43%) White patients. Inaddition, several new mutations were found in individual patient’s recurrentcompared to initial tumors. Conclusions Currently the treatment ofendometrial cancer is rapidly changing with molecular profiling becoming partof the standard of care. Additionally, it and is being incorporated intoclinical trials in this group of patients. The specific gene mutations and RNAexpression signatures that were observed in our small cohort need to bevalidated in larger cohorts to determine their impact.

ABSTRACT Bacterial growth substrates influence a variety of biological functions, including the biosynthesis and regulation of lipid intermediates. The extent of this rewiring is not well understood nor has it been considered in the context of virally infected cells. Here, we used a one-host-two-temperate phage model system to probe the combined influence of growth substrate and phage infection on host carbon and lipid metabolism. Using untargeted metabolomics and lipidomics, we reported the detection of a suite of metabolites and lipid classes for two Sulfitobacter lysogens provided with three growth substrates of differing complexity and nutrient composition (yeast extract/tryptone [complex], glutamate and acetate). The growth medium led to dramatic differences in the detectable intracellular metabolites, with only 15% of 175 measured metabolites showing overlap across the three growth substrates. Between-strain differences were most evident in the cultures grown on acetate, followed by glutamate then complex medium. Lipid distribution profiles were also distinct between cultures grown on different substrates as well as between the two lysogens grown in the same medium. Five phospholipids, three aminolipid, and one class of unknown lipid-like features were identified. Most (≥94%) of these 75 lipids were quantifiable in all samples. Metabolite and lipid profiles were strongly determined by growth medium composition and modestly by strain type. Because fluctuations in availability and form of carbon substrates and nutrients, as well as virus pressure, are common features of natural systems, the influence of these intersecting factors will undoubtedly be imprinted in the metabolome and lipidome of resident bacteria. IMPORTANCE Community-level metabolomics approaches are increasingly used to characterize natural microbial populations. These approaches typically depend upon temporal snapshots from which the status and function of communities are often inferred. Such inferences are typically drawn from lab-based studies of select model organisms raised under limited growth conditions. To better interpret community-level data, the extent to which ecologically relevant bacteria demonstrate metabolic flexibility requires elucidation. Herein, we used an environmentally relevant model heterotrophic marine bacterium to assess the relationship between growth determinants and metabolome. We also aimed to assess the contribution of phage activity to the host metabolome. Striking differences in primary metabolite and lipid profiles appeared to be driven primarily by growth regime and, secondarily, by phage type. These findings demonstrated the malleable nature of metabolomes and lipidomes and lay the foundation for future studies that relate cellular composition with function in complex environmental microbial communities.

In order to accurately parse the visual scene into distinct surfaces, it is essential to determine whether a local luminance edge is caused by a boundary between two surfaces or a shadow cast across a single surface. Previous studies have demonstrated that local chromatic cues may help to distinguish edges caused by shadows from those caused by surface boundaries, but the information potentially available in local achromatic cues like contrast, texture, and penumbral blur remains poorly understood. In this study, we develop and analyze a large database of hand-labeled achromatic shadow edges to better understand what image properties distinguish them from occlusion edges. We find that both the highest contrast as well as the lowest contrast edges are more likely to be occlusions than shadows, extending previous observations based on a more limited image set. We also find that contrast cues alone can reliably distinguish the two edge categories with nearly 70% accuracy at 40x40 resolution. Logistic regression on a Gabor Filter bank (GFB) modeling a population of V1 simple cells separates the categories with nearly 80% accuracy, and furthermore exhibits tuning to penumbral blur. A Filter-Rectify Filter (FRF) style neural network extending the GFB model performed at better than 80% accuracy, and exhibited blur tuning and greater sensitivity to texture differences. We compare human performance on our edge classification task to that of the FRF and GFB models, finding the best human observers attaining the same performance as the machine classifiers. Several analyses demonstrate both classifiers exhibit significant positive correlation with human behavior, although we find a slightly better agreement on an image-by-image basis between human performance and the FRF model than the GFB model, suggesting an important role for texture.

Background: Hidradenitis suppurativa (HS) predominantly affects women of childbearing age, and sex hormones are thought to play a role in HS pathogenesis. However, there is a paucity of data regarding the pattern of HS perimenstrual flares, as well as patient responses to hormone-based therapies. Objective: We aimed to characterize the temporal pattern of perimenstrual flares, as well as factors associated with perimenstrual flares. We also sought to investigate responses to hormonal therapies in women with HS. Methods: An anonymous web-based questionnaire was distributed to various online HS support groups in May 2020. Results: A total of 283 participants met the inclusion criteria as adult women who self-reported having HS and menstrual cycles. The majority (176 of 282 women; 62.4%) reported HS worsening with menses, and 86.9% (153 of 176 women) noted that perimenstrual HS flares occurred always or often. Most women (138 of 175 women; 78.9%) reported that their HS flared in the week preceding menses. Perimenstrual HS flares were more likely in women with a family history of HS compared with those without (49.6% vs. 28.2%; p = .019). More than a third of respondents who had been treated with spironolactone reported improvement of HS symptoms, but more than a quarter of participants who used medroxyprogesterone acetate or used a hormonal intrauterine device reported worsened HS symptoms. Conclusion: Female patients with HS have high rates of perimenstrual HS flares, specifically during the week preceding the onset of menses. Additional investigations on the role of sex hormones in HS pathogenesis and the efficacy of hormone-based therapies are warranted.

Abstract Easily accessible office-based procedures that require minimal resources may facilitate timely surgical management of hidradenitis suppurativa (HS). This review focuses on excision and unroofing as two surgical HS treatments that can be tailored to the outpatient setting. Fifty-five articles were included in our review, representing 3914 patients. The majority were retrospective studies (58%, n = 32), and the studies reported data both across patients and by number of treated lesions. Recurrence rates for unroofing (14.5%) were found to be half that of excision (30%) across patients (p = 0.015) and slightly lower across lesions [20% recurrence vs 26% for excision (p = 0.023)]. Complication rates at the lesion level were also significantly associated with procedure, with rates after excision more than double those after roofing (26% vs. 12%, p

Glacier thinning and retreat drives initial acceleration of glacier sliding and erosion, de-buttressing of steep valley walls, and destabilization of ice-marginal deposits and bedrock, which can lead to massive rock avalanching and accelerated incision of tributary watersheds. A compelling example of these changes occurred in Taan Fjord in SE Alaska due to the rapid thinning and retreat of Tyndall Glacier over the past half century. Increased glacier sliding speeds led to both increased rates of subglacial erosion and the evacuation of subglacially stored sediments into the proglacial basins. The shrinking glacier also exposed proglacial tributary watersheds to rapid incision and denudation driven by >350 m of baselevel fall in a few decades. Moreover, in October 2015 a large tsunamigenic landslide occurred at the terminus of Tyndall Glacier, largely due to thinning exposing oversteepened, unstable slopes. Sediment yields from the glacier, the landslide and the tributary watersheds, measured from surveys of the sediments in the fjord collected in 1999 and 2016, are compared to ongoing changes in glacier and fjord geometry to investigate the magnitude of glacial and paraglacial denudation in Taan Fjord during retreat. In the last 50 years, sediment yields from the glacier and non-glacial tributaries kept pace with the rapid rate of retreat, and were on par with each other. Notably, basin-averaged erosion rates from the paraglacial landscape were twice that from the glacier, averaging 58 ± 9 and 26 ± 5 mm a−1, respectively. The sharp increases in sediment yields during retreat observed from both the glacier and the adjacent watersheds, including the landslide, highlight the rapid evolution of landscapes undergoing glacier shrinkage.

Abstract Background Community pharmacies are important for health access by rural populations and those who do not have optimum access to the health system, because they provide myriad health services and are found in most communities. This includes the sale of non-prescription syringes, a practice that is legal in the USA in all but two states. However, people who inject drugs (PWID) face significant barriers accessing sterile syringes, particularly in states without laws allowing syringe services programming. To our knowledge, no recent studies of pharmacy-based syringe purchase experience have been conducted in communities that are both rural and urban, and none in the Southwestern US. This study seeks to understand the experience of retail pharmacy syringe purchase in Arizona by PWID. Methods An interview study was conducted between August and December 2018 with 37 people living in 3 rural and 2 urban Arizona counties who identified as current or former users of injection drugs. Coding was both a priori and emergent, focusing on syringe access through pharmacies, pharmacy experiences generally, experiences of stigma, and recommendations for harm reduction services delivered by pharmacies. Results All participants reported being refused syringe purchase at pharmacies. Six themes emerged about syringe purchase: (1) experience of stigma and judgment by pharmacy staff, (2) feelings of internalized stigma, (3) inconsistent sales outcomes at the same pharmacy or pharmacy chain, (4) pharmacies as last resort for syringes, (5) fear of arrest for syringe possession, and (6) health risks resulting from syringe refusal. Conclusions Non-prescription syringe sales in community pharmacies are a missed opportunity to improve the health of PWID by reducing syringe sharing and reuse. Yet, current pharmacy syringe sales refusal and stigmatization by staff suggest that pharmacy-level interventions will be necessary to impact pharmacy practice. Lack of access to sterile syringes reinforces health risk behaviors among PWID. Retail syringe sales at pharmacies remain an important, yet barrier-laden, element of a comprehensive public health response to reduce HIV and hepatitis C among PWID. Future studies should test multilevel evidence-based interventions to decrease staff discrimination and stigma and increase syringe sales.

To investigate the relationship between intestinal microbiota and SARS-CoV-2-mediated pathogenicity in a United States, majority African American cohort. We prospectively collected fecal samples from 50 SARS-CoV-2 infected patients, 9 SARS-CoV-2 recovered patients, and 34 uninfected subjects seen by the hospital with unrelated respiratory medical conditions (controls). 16S rRNA sequencing and qPCR analysis was performed on fecal DNA/RNA. The fecal microbial composition was found to be significantly different between SARS-CoV-2 patients and controls (PERMANOVA FDR-P = .004), independent of antibiotic exposure. Peptoniphilus, Corynebacterium and Campylobacter were identified as the three most significantly enriched genera in COVID-19 patients compared to controls. Actively infected patients were also found to have a different gut microbiota than recovered patients (PERMANOVA FDR-P = .003), and the most enriched genus in infected patients was Campylobacter, with Agathobacter and Faecalibacterium being enriched in the recovered patients. No difference in microbial community structure between recovered patients and uninfected controls was observed, nor a difference in alpha diversity between the three groups. 24 of the 50 COVID-19 patients (48%) tested positive via RT-qPCR for fecal SARS-CoV-2 RNA. A significant difference in gut microbial composition between SARS-CoV-2 positive and negative samples was observed, with Klebsiella and Agathobacter being enriched in the positive cohort. No significant associations between microbiome composition and disease severity was found. The intestinal microbiota is sensitive to the presence of SARS-CoV-2, with increased relative abundance of genera (Campylobacter, Klebsiella) associated with gastrointestinal (GI) disease. Further studies are needed to investigate the functional impact of SARS-CoV-2 on GI health.

Hidradenitis suppurativa (HS) is a highly prevalent, morbid inflammatory skin disease with limited treatment options. The major cell types and inflammatory pathways in skin of patients with HS are poorly understood, and which patients will respond to TNF-α blockade is currently unknown. We discovered that clinically and histologically healthy appearing skin (i.e., nonlesional skin) is dysfunctional in patients with HS with a relative loss of immune regulatory pathways. HS skin lesions were characterized by quantitative and qualitative dysfunction of type 2 conventional dendritic cells, relatively reduced regulatory T cells, an influx of memory B cells, and a plasma cell/plasmablast infiltrate predominantly in end-stage fibrotic skin. At the molecular level, there was a relative bias toward the IL-1 pathway and type 1 T cell responses when compared with both healthy skin and psoriatic patient skin. Anti–TNF-α therapy markedly attenuated B cell activation with minimal effect on other inflammatory pathways. Finally, we identified an immune activation signature in skin before anti–TNF-α treatment that correlated with subsequent lack of response to this modality. Our results reveal the fundamental immunopathogenesis of HS and provide a molecular foundation for future studies focused on stratifying patients based on likelihood of clinical response to TNF-α blockade.

The 5th Scientific Conference of the International Pemphigus and Pemphigoid Foundation (IPPF), “Pemphigus and Pemphigoid: A New Era of Clinical and Translational Science” was held in Orlando, Florida, on May 15–16, 2018. Scientific sessions covered recent, ongoing, and future clinical trials in pemphigus and bullous pemphigoid, disease activity and quality of life instruments, and the IPPF Natural History Study. Furthermore, the meeting provided an opportunity to hear firsthand from patients, investigators, and industry about their experience enrolling for clinical trials.

BackgroundHidradenitis suppurativa (HS) is associated with comorbidities that contribute to poor health, impaired life quality, and mortality risk.ObjectiveTo provide evidence-based screening recommendations for comorbidities linked to HS.MethodsSystematic reviews were performed to summarize evidence on the prevalence and incidence of 30 comorbidities in patients with HS relative to the general population. The screening recommendation for each comorbidity was informed by the consistency and quality of existing studies, disease prevalence, and magnitude of association, as well as benefits, harms, and feasibility of screening. The level of evidence and strength of corresponding screening recommendation were graded by using the Strength of Recommendation Taxonomy (SORT) criteria.ResultsScreening is recommended for the following comorbidities: acne, dissecting cellulitis of the scalp, pilonidal disease, pyoderma gangrenosum, depression, generalized anxiety disorder, suicide, smoking, substance use disorder, polycystic ovary syndrome, obesity, dyslipidemia, diabetes mellitus, metabolic syndrome, hypertension, cardiovascular disease, inflammatory bowel disease, spondyloarthritis, and sexual dysfunction. It is also recommended to screen patients with Down syndrome for HS. The decision to screen for specific comorbidities may vary with patient risk factors. The role of the dermatologist in screening varies according to comorbidity.LimitationsScreening recommendations represent one component of a comprehensive care strategy.ConclusionsDermatologists should support screening efforts to identify comorbid conditions in HS.

Hidradenitis suppurativa is a chronic inflammatory disease that disproportionately affects women of childbearing age. Hidradenitis suppurativa is characterized by painful nodules, abscesses, draining dermal tunnels, and scarring with a predilection for intertriginous sites, such as the axilla, groin, and breast regions. Delay in diagnosis and treatment of hidradenitis suppurativa often results in long-term sequelae leading to significant morbidity, and rarely mortality, in these patients. This clinical opinion suggests that obstetrician-gynecologists are uniquely poised to recognize early signs of hidradenitis suppurativa during routine well-woman examinations and initiate treatment or referral to dermatology. Herein, we provide clinical pearls for obstetrician-gynecologists caring for female patients with hidradenitis suppurativa, including strategies for comprehensive management and recommendations to improve the comfort of patients with hidradenitis suppurativa during examinations.

Hidradenitis suppurativa (HS) is a highly prevalent, morbid inflammatory skin disease with limited treatment options. The major cell types and inflammatory pathways in skin of patients with HS are poorly understood, and which patients will respond to TNF-α blockade is currently unknown. We discovered that clinically and histologically healthy appearing skin (i.e., nonlesional skin) is dysfunctional in patients with HS with a relative loss of immune regulatory pathways. HS skin lesions were characterized by quantitative and qualitative dysfunction of type 2 conventional dendritic cells, relatively reduced regulatory T cells, an influx of memory B cells, and a plasma cell/plasmablast infiltrate predominantly in end-stage fibrotic skin. At the molecular level, there was a relative bias toward the IL-1 pathway and type 1 T cell responses when compared with both healthy skin and psoriatic patient skin. Anti-TNF-α therapy markedly attenuated B cell activation with minimal effect on other inflammatory pathways. Finally, we identified an immune activation signature in skin before anti-TNF-α treatment that correlated with subsequent lack of response to this modality. Our results reveal the fundamental immunopathogenesis of HS and provide a molecular foundation for future studies focused on stratifying patients based on likelihood of clinical response to TNF-α blockade.

Hidradenitis suppurativa (HS) is a highly prevalent, morbid inflammatory skin disease with limited treatment options. The major cell types and inflammatory pathways in skin of patients with HS are poorly understood, and which patients will respond to TNF-α blockade is currently unknown. We discovered that clinically and histologically healthy appearing skin (i.e., nonlesional skin) is dysfunctional in patients with HS with a relative loss of immune regulatory pathways. HS skin lesions were characterized by quantitative and qualitative dysfunction of type 2 conventional dendritic cells, relatively reduced regulatory T cells, an influx of memory B cells, and a plasma cell/plasmablast infiltrate predominantly in end-stage fibrotic skin. At the molecular level, there was a relative bias toward the IL-1 pathway and type 1 T cell responses when compared with both healthy skin and psoriatic patient skin. Anti-TNF-α therapy markedly attenuated B cell activation with minimal effect on other inflammatory pathways. Finally, we identified an immune activation signature in skin before anti-TNF-α treatment that correlated with subsequent lack of response to this modality. Our results reveal the fundamental immunopathogenesis of HS and provide a molecular foundation for future studies focused on stratifying patients based on likelihood of clinical response to TNF-α blockade.

Cutaneous dysbiosis is implicated in hidradenitis suppurativa (HS) pathogenesis. Previous studies reveal skin microbiota shifts in HS lesional skin. In their report, Riverain-Gillet et al. (2020) extended these findings and reported skin microbiota shifts in unaffected HS skinfolds as well. Their study suggests that skin microbial shifts may precede clinical lesions and draws attention to study methods important for skin microbiome research.

Easily accessible office-based procedures that require minimal resources may facilitate timely surgical management of hidradenitis suppurativa (HS). This review focuses on excision and unroofing as two surgical HS treatments that can be tailored to the outpatient setting. Fifty-five articles were included in our review, representing 3914 patients. The majority were retrospective studies (58%, n = 32), and the studies reported data both across patients and by number of treated lesions. Recurrence rates for unroofing (14.5%) were found to be half that of excision (30%) across patients (p = 0.015) and slightly lower across lesions [20% recurrence vs 26% for excision (p = 0.023)]. Complication rates at the lesion level were also significantly associated with procedure, with rates after excision more than double those after roofing (26% vs. 12%, p

Hidradenitis suppurativa is a severe and debilitating dermatologic disease. Clinical management is challenging and consists of both medical and surgical approaches, which must often be combined for best outcomes. Therapeutic approaches have evolved rapidly in the last decade and include the use of topical therapies, systemic antibiotics, hormonal therapies, and a wide range of immunomodulating medications. An evidence-based guideline is presented to support health care practitioners as they select optimal medical management strategies and is reviewed in this second part of the management guidelines. A therapeutic algorithm informed by the evidence available at the time of the review is provided.

Hidradenitis suppurativa is a chronic inflammatory disorder affecting hair follicles, with profoundly negative impact on patient quality of life. Evidence informing ideal evaluation and management of patients with hidradenitis suppurativa is still sparse in many areas, but it has grown substantially in the last decade. Part I of this evidence-based guideline is presented to support health care practitioners as they select optimal management strategies, including diagnostic testing, comorbidity screening, and both complementary and procedural treatment options. Recommendations and evidence grading based on the evidence available at the time of the review are provided.

Background/Study Context: Memory for specific, verbatim details tends to decline with age, and reliance on gist-based information increases. However, instructions that direct attention toward certain types of information can benefit memory accuracy for that information. Previous work has examined gist-based and verbatim memory for images, but little work has utilized stimuli that participants may study in their daily lives, such as a weather forecast.MethodsThe current study examined how younger and older adults recall both general, gist-based information and specific, verbatim details of a weather forecast, and whether differences in the task instructions to focus on gist-based information may affect recall. Two study-test cycles with different forecasts were used to determine whether experience with the task may affect performance.ResultsWhile there was no effect of additional gist-based instructions on recall of gist-based information, participants who received the additional instructions recalled fewer verbatim details than those who did not. There were no age-related differences in recall of the gist of the forecast, but younger adults correctly recalled more verbatim details than older adults did.ConclusionEnvironmental support and use of gist-based processing can allow both younger and older adults to remember information that can be useful in their daily lives. The current study informs future research on prospective memory and memory for everyday information.

Matrix-assisted ionization (MAI) of inorganic analytes is a nascent research domain that holds promise for rapid, potentially facility-deployable analytical applications. We present results of MAI uranium isotopic analysis (235U/238U) obtained on the timescale of minutes utilizing simple sample preparation and an ambient ionization time-of-flight mass spectrometer (ToF MS). Experimental MAI-ToF MS characterization of uranium Certified Reference Materials (CRMs) was used to establish method calibration and validate quantitative 235U/238U determination spanning depleted, natural, and low-enriched uranium isotopic compositions. Secondary standard analyses with total uranium mass loadings of 5–500 ng per analysis yield accurate calibrated 235U/238U results and relative uncertainties of 4.7–17.2% (approx. ±95% confidence level), with weighted-mean uncertainties approaching 1.5%. This method permits accurate determination of uranium isotopic composition in a sample with uranium content as low as 200 pg for equal atom 235U:238U. Instrument detection limits constrain the minimum uranium mass required to identify the presence of highly enriched uranium (HEU ≥20% 235U) as only 500 pg using the method presented here. MAI-ToF MS quantitation of relatively extreme isotope ratios (235U/238U ≤ 0.01) is limited by detection of minor 235U (LoD 100 pg 235U/analysis ≈ 10 ng total U/analysis), and subsequent method optimization is anticipated to further reduce these limits. These findings underscore the potential of MAI-ToF MS for isotopic characterization of uranium and other inorganic species for both basic and applied science. [ABSTRACT FROM AUTHOR]