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Purpose of Review: This review aims to assess the landscape of in-office procedural management of HS. It evaluates the role of simple office procedures, such as steroid injections and incision and drainage (I&D), to the more complicated office surgical procedures, including deroofing and excisions with secondary intention healing, and innovative light and laser-based therapies. Recent Findings: Punch debridement (mini-deroofing) remains an underutilized in-office procedure for HS. While the neodymium-doped yttrium aluminum garnet (Nd: YAG) laser continues to be preferred for laser hair removal (LHR), recent evidence highlights the effectiveness of Alexandrite lasers. Minimally invasive approaches such as cryoinsufflation and intralesional photodynamic therapy (PDT) may be helpful for patients reluctant to undergo more invasive surgical procedures. Summary: In-office procedures are integral to managing HS in conjunction with medical therapies. These procedures enable a personalized approach to addressing the chronic and challenging nature of HS and improving quality of life.

•A standardized and validated robotic surgery curriculum is needed.•There is limited validity data to support Intuitive's latest VR simulator, SimNow.•This analysis generated validity evidence for 15 SimNow tasks and 3 inanimate tasks.•Appropriate curriculum content and scoring metrics may improve learning efficiency.

IMPORTANCE: Although several clinician- and patient-reported outcome measures have been developed for trials in hidradenitis suppurativa (HS), there is currently no consensus on which measures are best suited for use in clinical practice. Identifying validated and feasible measures applicable to the practice setting has the potential to optimize treatment strategies and generate generalizable evidence that may inform treatment guidelines. OBJECTIVE: To establish consensus on a core set of clinician- and patient-reported outcome measures recommended for use in clinical practice and to establish the appropriate interval within which these measures should be applied. EVIDENCE REVIEW: Clinician- and patient-reported HS measures and studies describing their psychometric properties were identified through literature reviews. Identified measures comprised an item reduction survey and subsequent electronic Delphi (e-Delphi) consensus rounds. In each consensus round, a summary of outcome measure components and scoring methods was provided to participants. Experts were provided with feasibility characteristics of clinician measures to aid selection. Consensus was achieved if at least 67% of respondents agreed with use of a measure in clinical practice. FINDINGS: Among HS experts, response rates for item reduction, e-Delphi round 1, and e-Delphi round 2 surveys were 76.4% (42 of 55), 90.5% (38 of 42), and 92.9% (39 of 42), respectively; among patient research partners (PRPs), response rates were 70.8% (17 of 24), 100% (17 of 17), and 82.4% (14 of 17), respectively. The majority of experts across rounds were practicing dermatologists with 18 to 19 years of clinical experience. In the final e-Delphi round, most PRPs were female (12 [85.7%] vs 2 males [11.8%]) and aged 30 to 49 years. In the final e-Delphi round, HS experts and PRPs agreed with the use of the HS Investigator Global Assessment (28 [71.8%]) and HS Quality of Life score (13 [92.9%]), respectively. The most expert-preferred assessment interval in which to apply these measures was 3 months (27 [69.2%]). CONCLUSIONS AND RELEVANCE: An international group of HS experts and PRPs achieved consensus on a core set of HS measures suitable for use in clinical practice. Consistent use of these measures may lead to more accurate assessments of HS disease activity and life outcomes, facilitating shared treatment decision-making in the practice setting.

IMPORTANCE: Patient-perceived barriers to hidradenitis suppurativa (HS) care are poorly understood. Understanding health care barriers is a critical first step toward improving care for this population. OBJECTIVE: To characterize the health care experiences of people living with HS, including perceived barriers and facilitators to health care access, and to elucidate potential associations among these barriers and facilitators, health care access, and disease activity. DESIGN, SETTING, AND PARTICIPANTS: In this qualitative study, an inductive thematic analysis was conducted on 45 in-depth, 60- to 90-minute semistructured interviews of 45 people with HS from diverse sociodemographic backgrounds that took place between March and April 2020. Individuals were eligible if they could speak English, were 18 years or older, and were diagnosed with HS. A diagnosis of HS was confirmed through physician diagnosis or through self-reported, affirmative response to the validated screening question, “Do you experience boils in your armpits or groin that recur at least every six months?” MAIN OUTCOMES AND MEASURES: Interviews were audio recorded and transcribed verbatim. A modified grounded theory approach was used to develop the codebook, which investigators used for inductive thematic analysis. RESULTS: Among the 45 participants included, the median (IQR) age was 37 (16) years, 33 (73%) were female, and 22 (49%) were White. There were 6 interrelated themes associated with participant-perceived barriers to accessing HS care: (1) bidirectional associations of disease activity and employment, (2) association of employment with health care coverage, (3) association of health care coverage with costs and perceived access to care, (4) association of costs with access to patient-centered care, (5) health care professional attitudes and knowledge influence patient-centered care and perceived access to care and disease activity, and (6) health system characteristics influence patient-centered care and associated costs, perceived access to care, and disease activity. CONCLUSIONS AND RELEVANCE: This qualitative study highlights themes that generate a conceptual model for understanding barriers that may act synergistically to limit health care access and influence disease activity. The disease activity of HS may be reduced when cycle elements are optimized. This study also highlights areas for future investigations and potential systems-level changes to improve access to patient-centered HS care.

IMPORTANCE: Hidradenitis suppurativa (HS) is associated with considerable diagnostic delay. Although most patients report adolescent onset, existing HS diagnostic criteria may not adequately capture disease in pediatric populations. OBJECTIVES: To determine the proportion of physician-diagnosed pediatric patients with HS who met diagnostic criteria, and describe demographics, disease characteristics, and diagnostic patterns among pediatric patients with HS. DESIGN, SETTING, AND PARTICIPANTS: In this retrospective, cross-sectional study, electronic medical records from 2 sites of a single academic tertiary care center were included. Eligible patients were those born after January 1, 1993, and assigned International Classification of Diseases, Ninth and Tenth Revisions (ICD-9/10) codes for HS (ICD-9 705.83/ICD-10 L73.2) between January 1, 2012, and July 1, 2021. Patients were excluded if they were older than 18 years at diagnosis, had inaccessible diagnostic visit notes, or were unintentionally assigned an HS ICD code. EXPOSURES: Pediatric patients with HS. MAIN OUTCOMES AND MEASURES: Fulfillment of diagnostic criteria in pediatric patients with HS. RESULTS: A total of 297 adolescents with HS were included in the study; 123 patients were female (78.1%), 78 self-identified as Black (26.3%), and 116 self-identified as Hispanic (39.1%). The median (IQR) age at diagnosis was 14.0 (13.0-16.0) years. Documentation from the diagnostic visit demonstrated that 127 (42.8%) patients did not meet all 3 major HS diagnostic criteria. Of these patients, 122 (96.1%) did not meet the recurrence interval criterion (≥2 lesions within 6 months). Overall, 96 patients who did not meet the recurrence interval criterion had documentation from additional visits in the health system; 59 (61.5%) had documentation of 1 or more additional lesions consistent with HS. Review of these additional records demonstrated that 26 of these 59 (44.1%) patients met the recurrence interval criterion after diagnosis, and 44 (74.6%) had recurrent lesions within a 1-year interval (median, 6.5 months; interquartile range, 3.5-12.2 months). Medical chart review was conducted from November 22, 2021, to January 12, 2022. Analysis was conducted from January 12, 2022, to January 15, 2022. CONCLUSIONS AND RELEVANCE: Overall, 118 (40%) of 297 pediatric patients with HS in this retrospective cross-sectional study did not meet all major diagnostic criteria at the time of diagnosis, largely due to failure to fulfill the 6-month recurrence interval criterion. Future studies are needed to determine the appropriate recurrence interval to facilitate timely diagnosis and promote clinical trial eligibility for pediatric patients with HS.

AbstractEarly nutritional and growth experiences can impact development, metabolic function, and reproductive outcomes in adulthood, influencing health trajectories in the next generation. The insulin-like growth factor (IGF) axis regulates growth, metabolism, and energetic investment, but whether it plays a role in the pathway linking maternal experience with offspring prenatal development is unclear. To test this, we investigated patterns of maternal developmental weight gain (a proxy of early nutrition), young adult energy stores, age, and parity as predictors of biomarkers of the pregnancy IGF axis (n= 36) using data from the Cebu Longitudinal Health and Nutrition Survey in Metro Cebu, Philippines. We analyzed maternal conditional weight measures at 2, 8, and 22 years of age and leptin at age 22 (a marker of body fat/energy stores) in relation to free IGF-1 and IGFBP-3 in mid/late pregnancy (mean age = 27). Maternal IGF axis measures were also assessed as predictors of offspring fetal growth. Maternal age, parity, and age 22 leptin were associated with pregnancy free IGF-1, offspring birth weight, and offspring skinfold thickness. We find that free IGF-1 levels in pregnancy are more closely related to nutritional status in early adulthood than to preadult developmental nutrition and demonstrate significant effects of young adult leptin on offspring fetal fat mass deposition. We suggest that the previously documented finding that maternal developmental nutrition predicts offspring birth size likely operates through pathways other than the maternal IGF axis, which reflects more recent energy status.

Introduction:Hidradenitis suppurativa (HS) patients may be at increased risk of COVID-19 infection and complications from their medications and comorbidities. There is a lack of expert consensus on recommendations for the COVID-19 vaccine for HS patients. Herein, we aim to provide expert-driven consensus recommendations regarding COVID-19 vaccinations in HS patients. Methods:A modified Delphi consensus survey developed by a core committee of 7 dermatologist HS experts consisting of 4 demographic questions and 12 practice statements was distributed to the US HS Foundation-sponsored provider listserv. Participants were attending physician HS experts. Survey results were to be reviewed by the core group and revised and resubmitted until consensus (≥70% agreement) was achieved. Results:Among the 33 survey participants, there were 30 (87%) dermatologists, 1 general surgeon, 1 plastic surgeon, and 1 rheumatologist. Consensus for all 12 statements on vaccine counseling and HS treatment counseling was achieved after the first round. Discussion/Conclusion:For now, this consensus can serve as a resource for clinicians discussing COVID-19 vaccination with their HS patients. These recommendations will need to be updated as new evidence on COVID-19 emerges.

IMPORTANCE: The identification and validation of biomarkers in hidradenitis suppurativa (HS) has potential to improve the understanding and management of this chronic, burdensome disease. OBJECTIVE: To systematically identify all known HS biomarkers, categorize them by biomarker type, and critically evaluate their validity according to established criteria. EVIDENCE REVIEW: Eligibility criteria for this review (PROSPERO Registration 230830) included randomized clinical trials, uncontrolled clinical trials, cohort studies, case-control studies, and other observational studies with no restrictions of patient age, sex, race or ethnicity, or language of publication up until December 31, 2020. All articles were categorized into biomarker type, defined using the US Food and Drug Administration Biomarkers, Endpoints, and other Tools (BEST) glossary. Assessment of each identified biomarker was undertaken in line with the US Food and Drug Administration and European Medicines Agency guidelines for the validation of proposed biomarkers. Assessment of the strength of overall data regarding individual biomarkers was undertaken using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach. FINDINGS: A total of 3953 nonduplicate articles were screened, of which 1429 articles were retrieved based on the include/exclusion criteria applied. After full-text screen and data extraction, 106 articles were included in this review. The evidence of strength of 6 categories of biomarkers (susceptibility/risk, diagnostic, monitoring, predictive, prognostic, and pharmacodynamic/response biomarkers) was assessed using GRADE criteria. A total of 48 biomarkers were identified with a minimum GRADE rating of moderate. Only 1 diagnostic (serum IL-2R), 1 monitoring (dermal Doppler vascularity), and 2 predictive biomarkers (epithelialized tunnels and positive family history of HS) achieved a GRADE rating of high. None of the identified biomarkers had sufficient clinical validity to be recommended for routine use in the clinical setting. CONCLUSIONS AND RELEVANCE: Major barriers to the identification, validation, and introduction of routine biomarkers in the management of HS include lack of independent biomarker validation studies (especially assumption-free “omics”-based techniques); insufficient assessment of collinearity between identified or proposed biomarkers; and a lack of routine integration of biomarkers into the structure of clinical trials. International consensus among researchers, clinicians, and pharmaceutical stakeholders is required to standardize goals and methods and encourage biomarker integration into future HS clinical trials. This systematic review presents a number of priorities for near-term future research to overcome such barriers and limitations of biomarkers in HS.

IMPORTANCE: Generalized pustular psoriasis (GPP) is a chronic, orphan disease with limited epidemiological data. OBJECTIVE: To describe the clinical characteristics, treatments, longitudinal disease course, and disease-specific health care utilization among patients with GPP across the United States. DESIGN, SETTING, AND PARTICIPANTS: A retrospective longitudinal case series involving 95 adults who met the European Rare and Severe Psoriasis Expert Network consensus definition for GPP and were treated at 20 US academic dermatology practices between January 1, 2007, and December 31, 2018. MAIN OUTCOMES AND MEASURES: The primary outcome is to describe the patient characteristics, associated medical comorbidities, treatment patterns complications, and GPP–specific health care utilization. RESULTS: Sixty-seven of 95 patients (70.5%) were women (mean age, 50.3 years [SD, 16.1 years]). In the initial encounter, 35 patients (36.8%) were hospitalized and 64 (67.4%) were treated with systemic therapies. In total, more than 20 different systemic therapies were tried. During the follow-up period, 19 patients (35.8%) reported hospitalizations at a median rate of 0.5 hospitalizations per year (IQR, 0.4-1.6). Women had a decreased risk of an emergency department or hospital encounter (odds ratio, 0.19; 95% CI, 0.04-0.83). CONCLUSIONS AND RELEVANCE: Generalized pustular psoriasis is a rare, chronic disease without standard treatment and is associated with continued health care utilization over time.

IMPORTANCE: Palmoplantar pustulosis (PPP) is a is a chronic, orphan disease with limited epidemiological data. OBJECTIVE: To describe the clinical characteristics, treatments, longitudinal disease course, and health care utilization in adults with PPP across the US. DESIGN, SETTING, AND PARTICIPANTS: This retrospective, longitudinal case series from 20 academic dermatology practices in the US included a consecutive sample of 197 adults who met the European Rare and Severe Psoriasis Expert Network consensus definition for PPP between January 1, 2007, and December 31, 2018. Data analysis was performed June 2020 to December 2020. MAIN OUTCOMES AND MEASURES: The primary outcome was to describe the patient characteristics, associated medical comorbidities, treatment patterns, complications, and PPP-specific health care utilization. RESULTS: Of 197 patients, 145 (73.6%) were female, and the mean (SD) age at presentation was 53.0 (12.6) years, with a mean (SD) follow-up time of 22.1 (28.0) months. On initial presentation, 95 (48.2%) patients reported skin pain, and 39 (19.8%) reported difficulty using hands and/or feet. Seventy patients (35.5%) were treated with systemic treatments, and use of more than 20 different systemic therapies was reported. In patients with at least 6 months of follow-up (n = 128), a median (IQR) of 3.7 (4-10) dermatology visits per year were reported; 24 (18.8%) patients had 5 or more visits during the study period. CONCLUSIONS AND RELEVANCE: In this case series, PPP was associated with persistent symptoms, continued health care utilization, and a lack of consensus regarding effective treatments, emphasizing the unmet medical need in this population. Additional research is necessary to understand treatment response in these patients.

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During the COVID-19 pandemic, rapid, real-world evidence is essential for the development of knowledge and subsequent public health response. In dermatology, provider-facing and patient-facing registries focused on COVID-19 have been important sources of research and new information aimed at guiding optimal patient care. The 7 dermatology registries included in this update now include more than 8000 case reports sourced from physicians and patients from countries all over the world.

To improve our understanding and guide future studies and applications, we review the biogeochemistry of the rare earth elements (REE). The REEs, which form a chemically uniform group due to their nearly identical physicochemical properties, include the lanthanide series elements plus scandium (Sc) and yttrium (Y). These elements, in conjunction with the neodymium isotopes, are powerful tools for understanding key oceanic, terrestrial, biological and even anthropogenic processes. Furthermore, their unique properties render them essential for various technological processes and products. Here, we delve into the characteristics of REE biogeochemistry and discuss normalization procedures and REE anomalies. We also examine the aqueous speciation of REEs, contributing to a better understanding of their behavior in aquatic settings, including the role of neodymium isotopes. We then focus on their environmental distribution, fractionation, and controlling processes in different environmental systems across the land‐ocean continuum. In addition, we analyze sinks, sources, and the mobility of REEs, providing insights into their behavior in these environments. We further investigate the sources of anthropogenic REEs and their bioavailability, bioaccumulation, and transfer along food webs. We also explore the potential effects of climate change on the cycling, mobility and bioavailability of REEs, underlining the importance of current research in this evolving field. In summary, we provide a comprehensive review of REE behavior in the environment, from their properties and roles to their distribution and anthropogenic impacts, offering valuable insights and pinpointing key knowledge gaps. Rare earth elements (REE) are powerful tracers of both natural and anthropogenic processes within terrestrial and ocean environmentsREE are controlled by absorption, adsorption/desorption, co‐precipitation, remineralization, and particle dissolutionREE are technology‐critical metals with broad applications in the future low‐carbon global economy Rare earth elements (REE) are powerful tracers of both natural and anthropogenic processes within terrestrial and ocean environments REE are controlled by absorption, adsorption/desorption, co‐precipitation, remineralization, and particle dissolution REE are technology‐critical metals with broad applications in the future low‐carbon global economy

IMPORTANCE: Hidradenitis suppurativa (HS) in pediatric patients has been understudied. Increased awareness and recognition of HS prevalence in children demand efforts to better understand this condition. OBJECTIVE: To describe the demographics, clinical features, treatment, associated comorbidities, and outcomes in a large cohort of pediatric patients with HS. DESIGN, SETTING, AND PARTICIPANTS: International, multicenter, retrospective medical record review of pediatric patients (aged 1-18 years) with a clinical diagnosis of HS carried out in 10 dermatology clinics across the US, Canada, Israel, Australia, and Italy from January 1996 to January 2017. MAIN OUTCOMES AND MEASURES: Patient demographics, clinical features, severity, associated comorbidities, and treatments in pediatric patients with HS. RESULTS: This cross-sectional study included 481 patients diagnosed with HS. Overall, 386 (80%) were girls. The mean (SD) age of disease onset was 12.5 (2.9) years, and the mean (SD) age at diagnosis was 14.4 (3.5) years. Family history of HS was present in 111 of 271 (41%) patients. First signs/symptoms reported at disease onset were cyst/abscess in 229 of 481 (48%), pain/tenderness in 118 of 481 (25%), and papules/pustules in 117 of 481 (24%). At initial dermatologic assessment, 233 of 481 (48%) patients already had evidence of skin scarring. Disease severity (Hurley staging) was documented in 288 of 481 (60%) patients (47% stage 1, 45% stage 2 and 8% stage 3). Comorbid conditions were reported in 406 of 481 (85%) patients, the most common being obesity (263/406 [65%]) and acne vulgaris (118/406 [29%]). Complications occurred in 378 of 481 (79%) patients, the most common of which were scars or contractures (301/378 [80%]). CONCLUSIONS AND RELEVANCE: The findings of this study indicate that there is a gap in recognizing and diagnosing pediatric HS. Pediatric patients with HS are likely to present with other comorbidities. Prospective observational and interventional studies are needed to better understand clinical course and optimal treatments for pediatric HS.

IMPORTANCE: Hidradenitis suppurativa (HS) disproportionately affects women of childbearing potential. There is a paucity of data regarding the HS disease course during pregnancy and in the postpartum period. OBJECTIVE: To explore the HS disease course during pregnancy and in the postpartum period. DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort study was conducted on patients in the Henry Ford Health System, Detroit, Michigan—a large, academic, urban referral center. Women with a diagnosis of HS who became pregnant between January 1, 2008, and December 31, 2018, were included. International Classification of Diseases, Ninth Revision, and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, were used for identification of the diagnosis. EXPOSURES: Pregnancy in patients with HS. MAIN OUTCOMES AND MEASURES: Hidradenitis suppurativa disease status during pregnancy and the postpartum period. RESULTS: A total of 127 women with HS were included in this study and accounted for 202 pregnancies. Of the 202 pregnancies, 171 were in black women, 25 in white women, 3 in women of other race/ethnicity, and 3 had unreported data. Mean (SD) age at HS onset was 19.3 (5.6) years; at time of HS diagnosis, 24.4 (5.3) years; and at time of pregnancy, 25.9 (5.0) years. The disease worsened during pregnancy in 70 pregnancies (61.9%), did not change in 34 pregnancies (30.1%), and improved in 9 pregnancies (8.0%). Hidradenitis suppurativa exacerbated in the postpartum period after 82 of 124 pregnancies (66.1%). Dermatologists were involved in managing HS in 28 pregnancies (14.4%) and for a higher proportion of patients with more severe Hurley stage as compared with cases of mild disease (stage 3: 7 of 18 [38.9%] vs stage 1: 10 of 100 [10.0%] or stage 2: 11 of 67 [16.4%]; P = .004). In addition, HS medical treatment was administered during 77 pregnancies (38.1%), while HS procedural treatment was administered during 34 pregnancies (16.8%). A significantly higher proportion of patients whose care was managed by dermatologists vs those without dermatologist involvement received any HS medication (22 [78.6%] vs 53 [31.7%], P < .001) or any HS procedure (14 [50%] vs 19 [11.4%], P < .001) during pregnancy. CONCLUSIONS AND RELEVANCE: Despite a high rate of HS exacerbation during pregnancy and postpartum, this cohort study found that most of the patients did not receive HS-directed medical treatment or care from a dermatologist during pregnancy. Close monitoring and improved collaborative care between dermatology and obstetrics-gynecology services is warranted.

Choices about fracturing fluid additives can affect production. Special Focus: PRODUCTION TECHNOLOGY Optimizing surfactants to improve stimulation flowback in tight gas wells Choices about fracturing fluid additives can affect production. [...]

Photo essay with text of the current wars in Burma (Myanmar), a country which has made isolation a national cult for almost 42 years and home to the world's longest-running insurgency. INSET: A rebel who's who..

Enabling light-controlled ionic devices requires insight into photoionic responses in technologically relevant materials. Mixed-conducting perovskites containing nondilute Fe─serving as electrodes, catalysts, and sensors─can support large, electronically accommodated excursions in oxygen content, typically controlled by temperature, bias, and gas atmosphere. Instead, we investigated the ability of low-fluence, above-bandgap illumination to adjust oxygen stoichiometry and drive oxygen fluxes in nondilute Sr(Ti1–xFex)O3–x/2+δ(x= 0.07, 0.35) thin films with high baseline hole concentrations. Films’ optical transmission at 2.8 eV was used as a probe of oxygen stoichiometry in the range ∼100–500 °C. We compared pO2-step-driven and UV (3.4 eV)-step-driven visible optical transmission relaxations in films, finding that the time constants and activation energies of the relaxations were consistent with each other and thus with oxygen-surface-exchange-limited kinetics. Blocking oxygen exchange at the solid–gas interface with a UV-transparent capping layer resulted in no UV-induced optical relaxations. These results demonstrate that above-bandgap illumination can increase oxygen content in nondilute compositions through oxygen flux into the solid from the gas. First-principles simulations of defect formation enthalpies indicate that oxygen vacancies are energetically less favorable under steady-state illumination owing to shifts in quasi-Fermi levels. A larger 2.8 eV-optical response to UV illumination in x= 0.07 vs x= 0.35 samples was further investigated through ultrafast transient spectroscopy, where it was found that the x= 0.07 sample exhibits a slower carrier recombination. Together, these results suggest potential design principles for materials supporting large stoichiometry changes under above-gap illumination: (1) long excited carrier lifetimes and (2) highly charged, rather than neutral, defects/associates.

Methods for describing and reporting the clinical and histological characteristics of cutaneous tissue samples from patients with hidradenitis suppurativa (HS) are not currently standardized, limiting clinicians’ and scientists’ ability to uniformly record, report, and communicate about the characteristics of tissue used in translational experiments. A recently published consensus statement outlined morphological definitions of typical HS lesions, but no consensus has been reached regarding clinical characterization and examination of HS tissue samples. Here we aimed to establish a protocol for reporting histopathologic and clinical characteristics of HS tissue specimens. This study was conducted from May 2023 to August 2023. Experts in clinical care, dermatopathology, and translational research were recruited, and a modified Delphi technique was used to develop a protocol for histologic reporting and clinical characterization of submitted tissue specimens from HS patients. A total of 27 experts participated (14 dermatologists, 3 fellowship-trained dermatopathologists, 3 plastic surgeons, 3 general surgeons, and 4 research scientists) in creating and reviewing protocols for the clinical and histopathological examination of HS tissue specimens. The protocols were formatted as a synoptic report and will help consistently classify specimens in biobanks based on histological features and more accurately report and select samples used in translational research projects.

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.

In November 2017, a formal debate on the role of bacteria in the pathogenesis of hidradenitis suppurativa (HS) was held at the 2nd Symposium on Hidradenitis Suppurativa Advances (SHSA) in Detroit, Michigan. In this report, we present both sides of the argument as debated at the SHSA meeting and then discuss the potential role of bacteria as classic infectious pathogens versus an alternative pathogenic role as activators of dysregulated commensal bacterial-host interactions. Although there was consensus that bacteria play a role in pathogenesis and thus are pathogenic, there was a compelling discussion about whether bacteria in HS incite an infectious disease as we classically understand it or whether bacteria might play a different role in HS pathogenesis.

Methane fluxes into the oceans are largely dependent on the methane phase as it migrates upward through the sediments. Here we document decoupled methane transport by gaseous and aqueous phases in Storfjordrenna (offshore Svalbard) and propose a three‐stage evolution model for active seepage in the region where gas hydrates are present in the shallow subsurface. In a preactive seepage stage, solute diffusion is the primary transport mechanism for methane in the dissolved phase. Fluids containing dissolved methane have high 87Sr/86Sr ratios due to silicate weathering in the microbial methanogenesis zone. During the active seepage stage, migration of gaseous methane results in near‐seafloor gas hydrate formation and vigorous seafloor gas discharge with a thermogenic fingerprint. In the postactive seepage stage, the high concentration of dissolved lithium points to the contribution of a deeper‐sourced aqueous fluid, which we postulate advects upward following cessation of gas discharge. How methane moves in the marine sediment, as a gas or a dissolved component, determines the environmental impact of this important greenhouse gas. In contrast to observations of biosphere activity beeing supported by dissolved methane, free gas methane cannot be used by microorganisms and can escape to the ocean more easily. Here we report the different ways methane moves in the sediments of an Arctic methane seep. We show that methane moves as free gas during the most active stage and as a dissolved component in the pore water before and after the most active period. Our results show that the supply of free gas methane in the sediments can explain why some of the seafloor features in our study area are more active than the others. We document the decoupled gaseous and aqueous fluid phases from Storfjordrenna, a cold seep south of SvalbardWe propose a three‐stage evolution model with different modes of methane transport in each stageThe evolution of the seepage is controlled by the availability of gaseous methane and/or the development of fluid conduits

The article offers suggestions for preventing scours in dairy calves. It mentions that early detection is key in preventing death caused by scours as rectal temperature can help determine the presence of scour-causing bacteria. It states that immunoglobulins present in the colostrum, are used to light the diarrhea-inducing bacteria that the calf may encounter and antibodies within colostrum will not be absorbed if not ingested soon after birth.

Supplemental Digital Content is available in the text.

IMPORTANCE: Cutaneous leiomyomas can be associated with severe paroxysmal pain in which nerve conduction may have a key role. Medical management of painful cutaneous leiomyomas is generally unsatisfactory. OBJECTIVE: To assess the efficacy of intralesional botulinum toxin A in the management of pain associated with cutaneous leiomyomas. DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-blind, placebo-controlled pilot study conducted from January 5, 2009, to March 27, 2014. The setting was a single-center study at the National Institutes of Health among participants 18 years or older with cutaneous leiomyomas characterized by pain at least once weekly and pain of at least 4 on a pain scale ranging from 0 to 10. INTERVENTIONS: Eighteen participants were randomized to receive intralesional botulinum toxin A (5 U per 1 cm2) or equivalent volumes of intralesional saline placebo. MAIN OUTCOMES AND MEASURES: The primary outcomes were the differences in average lesional pain assessed by the Brief Pain Inventory and visual analog scale before and after ice provocation over a 4-week period. RESULTS: No significant difference in average lesional pain was observed between the study arms. Decreased pain was reported in the botulinum toxin vs placebo arms by visual analog scale scores before ice provocation (median, 0.00; range, −3.30 to 0.70 for botulinum toxin and median, 0.40; range, −1.30 to 1.50 for placebo; P = .06); however, this finding was nonsignificant. No significant difference was observed in change in pain after ice provocation. A significant difference was seen between the arms in skin-related quality of life by total Dermatology Life Quality Index (median, −4.00; range, −8.00 to 2.00 for botulinum toxin and median, 0.00; range, −1.00 to 4.00 for placebo; P = .007) and with the specific skin pain–related question on the Dermatology Life Quality Index (median, −1.00; range, −2.00 to 1.00 for botulinum toxin and median, 0.00; range, −1.00 to 0.00 for placebo; P = .048). No significant difference was found in pain as ascertained by Patient Global Impression of Change at week 4. No serious adverse events related to botulinum toxin use were observed. CONCLUSIONS AND RELEVANCE: The use of botulinum toxin to treat painful cutaneous leiomyomas was associated with improved quality of life and with a trend toward improved pain at rest. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00971620

IMPORTANCE: Cutaneous manifestations of chronic graft-vs-host disease (GvHD) are highly variable and may recapitulate well-characterized autoimmune diseases, including systemic sclerosis and Sjögren syndrome. However, vitiligo and alopecia areata (AA) have not been well characterized in the chronic GvHD setting. OBJECTIVE: To determine laboratory markers, transplant-related factors, and other systemic manifestations associated with vitiligo and/or AA in patients with chronic GvHD. DESIGN, SETTING, AND PARTICIPANTS: A cross-sectional, retrospective study conducted by the National Institutes of Health (NIH) of 282 adult and pediatric patients with chronic GvHD seen under the NIH natural history protocol between 2004 and 2013. MAIN OUTCOMES AND MEASURES: Demographic, clinical, and laboratory data, including measures of 11 antibodies, were included in the analysis. Patients with vitiligo and/or AA were identified from dermatologist documentation and photographic evidence. Univariate and multivariable logistic regression analyses were used to determine risk factors for vitiligo and AA development. RESULTS: Fifteen (5.3%) of 282 patients demonstrated vitiligo (14 of 282; 4.9%) and/or AA (2 of 282; 0.7%) (1 patient had both vitiligo and AA). Univariate analysis identified female donor to male recipient sex mismatch (P = .003), positive test results for anticardiolipin (ACA) IgG (P = .03) or antiparietal antibody (P = .049), elevated CD19 level (P = .045), and normal or elevated IgG level (P = .02) as risk factors for vitiligo or AA. Female donor to male recipient sex mismatch (P = .003) and positive findings for ACA-IgG (P = .01) retained significance in the multivariable analysis. CONCLUSIONS AND RELEVANCE: Female donor and female donor to male recipient sex mismatch, in particular, are significantly associated with the development of vitiligo and/or AA. Further studies are needed to explore transplant-related risk factors that may lead to better understanding of the pathomechanisms of chronic GvHD.

The article reports on the victory of the U.S. Soccer Federation (USSF) and Major League Soccer (MLS) in an antitrust and Racketeer Influenced Corrupt Organizations (RICO) case. Judge Harry Leinenweber of the U.S. District Court for the Northern District of Illinois gave judgement in favour of MLS and USSF and dismissed a lawsuit by ChampionsWorld LLC. ChampionsWorld filed a case claiming that USSF did not have authorization to ask payments for matches that ChampionsWorld promoted in the U.S.

This retrospective study of formalin-fixed infiltrating breast cancer specimens compared manual immunohistochemical assay with a new image analyzer-assisted immunohistochemical quantitation method, using fluorescence in situ hybridization assay (FISH) as the standard. Following the manual immunohistochemical assay, 189 cases, including most manual immunohistochemically positive and some random negative cases, were analyzed by FISH assay for Her-2/neu gene amplification and by the Automated Cellular Imaging System (ACIS) for immunohistochemical staining. Using the FISH standard, the ACIS immunohistochemical assay attained a higher concordance rate and sensitivity than the manual immunohistochemical assay (91.0% and 88% vs 85.7% and 71%, respectively), with only a slight decrease in specificity (93% vs 96%, respectively). In particular, the ACIS immunohistochemical assay resulted in a higher correlation with the FISH assay in the manual immunohistochemical assay 2+ cases. The ACIS immunohistochemical assay achieved higher accuracy than the manual method according to receiver operating characteristic curve analysis. The ACIS method represents a substantial improvement over the manual method for objective evaluation of the HER-2/neu status.

In the current work, we demonstrate ligand design concepts that significantly improve the superoxide dismutase (SOD) activity of a zinc complex; the catalysis is enhanced when two quinol groups are present in the polydentate ligand. We investigate the mechanism through which the quinols influence the catalysis and determine the impact of entirely removing a chelating group from the original hexadentate ligand. Our results suggest that SOD mimicry with these compounds requires a ligand that coordinates Zn(II) strongly in both its oxidized and reduced forms and that the activity proceeds through Zn(II)-semiquinone complexes. The complex with two quinols displays greatly enhanced catalytic ability, with the activity improving by as much as 450% over a related complex with a single quinol. In the reduced form of the diquinol complex, one quinol appears to coordinate to the zinc much more weakly than the other. We believe that superoxide can more readily displace this portion of the ligand, facilitating its coordination to the metal center and thereby hastening the SOD reactivity. Despite the presence of two redox-active groups that may communicate through intramolecular hydrogen bonding and redox tautomerism, only one quinol undergoes two-electron oxidation to a para-quinone during the catalysis. After the formation of the para-quinone, the remaining quinol deprotonates and binds tightly to the metal, ensuring that the complex remains intact in its oxidized state, thereby maintaining its catalytic ability. The Zn(II) complex with the diquinol ligand is highly unusual for a SOD mimic in that it performs more efficiently in phosphate solution.

A new active site directed photoaffinity probe, which is a model compound for studying nucleotide diphosphate sugar binding proteins, has been synthesized by coupling 5-azido-UTP and [32P]Glc-1-P using yeast UDP-glucose pyrophosphorylase to produce [β-32P]5-azidouridine 5′-diphosphoglucose (5N3UDP-Glc). This probe has photochemical properties similar to that of 5-azidoUTP (Evans, R. K., and Haley, B. E. (1987) Biochemistry26, 269–276). The efficacy of 5N3UDP-Glc as an active site directed probe was demonstrated using yeast UDP-Glc pyrophosphorylase. Saturation effects of photoinsertion were observed with an apparent Kdof 51 µMand the natural substrate, UDP-Glc, prevented photoinsertion of [β-32P]5N3UDP-Glc with an apparent Kdof 87 µM. Prevention of photoinsertion was also seen with UTP and pyrophosphate with apparent Kdvalues less than 200 µM. UMP, UDP, ATP, and GTP were much less effective competitors. Selective photoinsertion was observed with several partially purified enzymes including UDP-Glc dehydrogenase, UDP-Gal-4-epimerase, Gal-1-P uridyltransferase, and phosphorylase a. The absence of nonselective photoinsertion into bulk proteins was demonstrated with crude homogenates of rabbit liver as well as with several UDP-Glc binding proteins. Of the six purified enzymes tested, only phosphoglucomutase has been shown to incorporate radiolabel from the photoprobe in the absence of UV irradiation. These results and a discussion of the utility of 5N3UDP-Glc for detecting UDP-Glc binding proteins and isolating active site peptides are presented.

In this report, 8- and 2-azidoadenosine 5'-[gamma-32P]triphosphate were used to examine cerebrospinal fluid (CSF) samples for the presence of an ATP binding protein unique to individuals with Alzheimer disease (AD). A 42-kDa ATP binding protein was found in the CSF of AD patients that is not observed in CSF from normal patients or other neurological controls. The photolabeling is saturated with 30 microM 2-azidoadenosine 5'-[gamma-32P]triphosphate. Photoinsertion can be totally prevented by the addition of 25 microM ATP. Photoinsertion of 2-azidoadenosine 5'-triphosphate into the protein is only weakly protected by other nucleotides such as ADP and GTP, indicating that this is a specific ATP binding protein. A total of 83 CSF samples were examined in a blind manner. The 42-kDa protein was detected in 38 of 39 AD CSF samples and in only 1 of 44 control samples. This protein was identified as glutamine synthetase [GS; glutamate-ammonia ligase; L-glutamate:ammonia ligase (ADP-forming), EC 6.3.1.2] based on similar nucleotide binding properties, comigration on two-dimensional gels, reaction with a polyclonal anti-GS antibody, and the presence of significant GS enzyme activity in AD CSF. In brain, GS plays a key role in elimination of free ammonia and also converts the neurotransmitter and excitotoxic amino acid glutamate to glutamine, which is not neurotoxic. The involvement of GS, if any, in the onset of AD is unknown. However, the presence of GS in the CSF of terminal AD patients suggests that this enzyme may be a useful diagnostic marker and that further study is warranted to determine any possible role for glutamate metabolism in the pathology of AD.

The photoaffinity analog [32P]8-N3cAMP (8-azido adenosine 3′,5′-monophosphate was used to analyze the membrane sidedness of rat sperm cAMP binding proteins during epididymal maturation. Evidence is presented here which supports the hypothesis that 35–45% of the regulatory subunits of the Type I and Type II cAMP-dependent protein kinases are readily available to externally added cyclic nucleotide. It was observed by sodium dodecyl sulfate gel electrophoresis (SDS-PAGE) and autoradiography that only two rat sperm proteins (Mr= 49K and 55K) were photolabeled which comigrated on gels with partially purified Type I and Type II regulatory subunits, respectively. Both of these photolabeled epididymal sperm proteins were saturated at physiological titers of [32P]8-N3cAMP and photoincorporation of [32P]8-N3cAMP was specific since other SDS-resolvable sperm proteins did not photoincorporate the analog. Caput and cauda sperm protein photoincorporation could be effectively blocked by low levels of cAMP, but not by cGMP, ATP or GTP. Sperm epididymal maturation coincided with changes in the cAMP-dependent protein kinase subunits since cauda sperm contained more available Type II than did caput sperm. A subcellular analysis of cAMP-dependent protein kinase regulatory subunit in head and tail fractions was done for caput and cauda sperm and demonstrated that the tail fractions showed more photo-labeling of both Type I and II regulatory subunits than did the head fractions.

In an effort to identify the polypeptide chain of glucosylphosphodolichol synthase (EC 2.4.1.117), yeast microsomal membranes were allowed to react with 5-azido[beta-32P]UDPGlc, a photoactive analogue of UDPGlc, which is a substrate for this enzyme. Upon photolysis the 32P-labeled probe was shown to link covalently to a 35-kDa protein present in microsomal membranes prepared from several wild-type yeast strains. Binding was either reduced or absent in the microsomal membranes from two yeast mutants (alg5 and dpg1) that are known to be defective in the synthesis of glucosylphosphodolichol. The microsomes isolated from a heterozygous diploid strain alg5::dpg1 generated from these two mutants exhibited partial restoration of both the ability to photolabel the 35-kDa protein and the ability to catalyze the synthesis of glucosylphosphodolichol. Microsomal membranes from a mutant strain that synthesized glucosylphosphodolichol but lacked the ability to transfer the glucosyl residue to the growing lipid-linked oligosaccharide (alg6) exhibited labeling with 5-azido[beta-32P]UDPGlc comparable to that found in microsomes from the wild-type strain. In all cases photoinsertion of the probe into the 35-kDa protein correlated with the level of synthase assayed in the microsomal membranes. These results strongly support the conclusion that the 35-kDa protein labeled in these experiments is a component of glucosylphosphodolichol synthase.