The buffalo is an important species in many regions of the world, particularly in Asia, Africa and parts of Europe. Among the various species of buffalo, the water buffalo (Bubalus bubalis) is the most widespread, and it is well-known for its ability to thrive in wet and humid environments. In Europe, Italy is one of the leading producers of buffalo milk, and is particularly renowned for the production of Mozzarella di Bufala, a cheese made from the milk of water buffalo. Scientific knowledge on applied physiology, health, husbandry and reproduction in buffalo remains limited. This may be partly due to the fact that the species has historically been of greatest economic importance in regions where production systems are predominantly traditional and research investment has been limited. More recently, research has increasingly focused on production and feeding strategies and breeding practices. In addition, much of the research on the reproductive biology and management has concentered on the female buffalo, with particular emphasis on seasonality, oestruses detection and induction, whereas relatively little attention has been paid to male reproduction.This review discusses the reproductive physiology and behaviour of the male domestic buffalo in relation to differences in management and environmental conditions under which the species is reared, with a particular focus on the Italian Mediterranean buffalo breed (IMB).
The 2022 transition of United States Medical Licensing Examination (USMLE) Step 1 from numeric to pass/fail scoring represents a fundamental shift in neurosurgery residency applicant selection. Historically, Step 1 scores served as a key objective metric. With numeric scores no longer available, programs may place greater emphasis on alternative metrics. To the authors' knowledge, this study is the first that aimed to evaluate how predictors of neurosurgery match outcomes have shifted before and after Step 1 became pass/fail. We conducted a retrospective cohort analysis of neurosurgery residency applicant data from pre-pass/fail (Step 1 numeric) and post-pass/fail eras. Data were used from the 2023 and 2024 application cycles. Variables included demographics, USMLE Step 2 clinical knowledge (CK) scores, Step 1 pass status, research output variables, dedicated research years, postgraduate training after medical school graduation, Alpha Omega Alpha (AOA) membership, home institution status, and other academic metrics. Descriptive statistics were compared for matched and unmatched applicants within each era. Independent predictors of match success were identified through multivariable logistic regression analysis. In the pre-pass/fail era, matched applicants had higher Step 2 CK scores and more review article, neurosurgery-specific, neurosurgery-specific first-author, and total publications than unmatched applicants (p < 0.001 for all). Independent predictors of match success included Step 2 CK score and review article productivity. Research year and postgraduate training were negative predictors. In the post-pass/fail era, Step 2 CK, home institution, AOA membership, research year, neurosurgery-specific publications, and basic science publications were significant positive predictors. Review articles no longer predicted match success. The transition to pass/fail Step 1 has shifted the emphasis of neurosurgery residency applicant selection from general research productivity and review articles toward specialty-specific scholarship, home institution affiliation, AOA membership, and dedicated research experience. Step 2 CK has remained a consistent predictor across eras.
Major advances in pulp biology, biomaterials, and tissue engineering have fuelled the development of regenerative strategies aimed at preserving or restoring pulp vitality. Despite this progress, the clinical translation of these discoveries remains limited or absent. Although there is a global agenda to reduce and replace animal use in medical research, we believe that a critical missing link in the translational pipeline of regenerative endodontics innovations is the lack of rigorously validated, clinically relevant preclinical models to use in advancing promising in vitro findings through regulatory processes to human application. While novel alternative methodologies (NAMs), including microfluidics, organoids, and organ-on-chip systems, offer human-relevant in vitro models and are rapidly transforming early-stage screening and mechanistic studies, they are currently insufficient to replicate the complex systemic elements provided by animal models, which are essential for demonstrating in vivo efficacy of regenerative therapies. Regulatory approval of devices, drugs, and biologics continues to require robust preclinical evidence generated in whole-organism systems, particularly when complex interactions involving immunity, vascularisation, innervation, and aging are central to therapeutic success. In this perspective article, we discuss key scientific, methodological, and logistical considerations for the systematic development and validation of orthotopic animal models in regenerative endodontics research. We place particular emphasis on vital pulp treatment as a biologically and clinically relevant framework for studying pulp repair and in demonstrating the efficacy of novel therapies. We highlight the challenges that have hindered consensus in model selection and standardisation, and emphasise the need for coordinated transdisciplinary efforts to overcome these barriers. We argue that prioritising standardised orthotopic vital pulp treatment models, in combination with evolving NAMs, represents a critical step to bridge the gap between mechanistic discoveries and clinical translation in regenerative endodontics.
Older adults with cognitive disorders, including dementia and mild cognitive impairment, are particularly vulnerable to adverse effects from centrally acting medications. Cognitive potentially inappropriate medications (CogPIMs), including anticholinergics, antipsychotics, benzodiazepines (BZDs), and non-benzodiazepine hypnotics (Z-drugs), may worsen well-being and increase healthcare utilization in this population. This study evaluates CogPIMs exposure and its association with health-related quality of life (HRQoL) and healthcare utilization among community-dwelling older adults with cognitive disorders. We conducted a cross-sectional analysis of 2011-2022 Medical Expenditure Panel Survey (MEPS) data from adults aged ≥ 65 with cognitive disorders. CogPIMs exposure was defined as ≥ 1 prescription of anticholinergics, antipsychotics, BZDs, or Z-drugs. Outcomes included (1) annual prevalence of CogPIMs exposure, (2) healthcare utilization, and (3) HRQoL measured by SF-12 physical and mental component scores. Inverse probability of treatment weighting was used to adjust for confounding. Temporal trends were assessed using Joinpoint regression. Survey-weighted logistic and negative binomial regression models estimated adjusted associations. A total of 2796 older adults with cognitive disorders were identified in MEPS from 2011 to 2022, representing a weighted analytic sample of 29.7 million individuals. Overall CogPIM exposure declined from 39.3% in 2011 to 29.3% in 2022 (Annual Percentage Change: -1.9%, p < 0.01). CogPIM exposure was not associated with poor physical HRQoL but was associated with higher odds of poor mental HRQoL (adjusted Odds Ratio: 1.72 [1.31-2.25], p < 0.01). CogPIM exposure was also associated with higher rates of emergency department visits (adjusted incidence rate ratios (aIRR) = 1.41 [1.24-1.60], p < 0.01) and hospitalizations (aIRR = 1.38 [1.19-1.59], p < 0.01), but not outpatient visits (aIRR = 1.27 [0.75-1.54], p = 0.31). Among community-dwelling older adults with cognitive disorders, CogPIM exposure remains common and is associated with poorer mental HRQoL and increased acute care utilization. Future longitudinal and interventional studies are needed to determine whether modifying exposure to CogPIM can improve well-being and reduce potentially preventable acute care utilization.
Strict adherence to follow-up ophthalmic care after emergency department visits is critical not only for monitoring disease progression, assessing therapeutic response, and preventing avoidable complications, but also because ophthalmic examinations may provide one of the few opportunities to identify otherwise unrecognized systemic disease. To identify variables associated with loss to follow-up (LTFU) care after emergency department ophthalmology consultations, and to characterize similarities and differences between self-reported race. Retrospective cohort study examining emergency department ophthalmology consultations between January 1st, 2019, and December 31st, 2021, at a level 1 trauma center serving Western New York, Northern Pennsylvania and Southern Ontario. Single center study at Erie County Medical Center in Buffalo, New York, USA. A total of 2323 ophthalmology consultations were analyzed. The primary outcome was the rate of LTFU, defined as failure to attend a scheduled outpatient appointment. Demographic, diagnostic, and socioeconomic variables were analyzed across all patients and stratified by self-reported racial group (White, African American/Black, and Other). Logistic regression analysis was performed. Of the 1697/2323 (73.1%) patients that required an outpatient follow-up at The Ira G. Ross Eye Institute, 1003 (59.1%) identified as White, 489 (28.8%) identified as African American/Black and 205 (12.1%) identified as Other. The overall rate of LTFU was 41.8%, with no significant difference in follow-up rates by racial group on multivariable analysis. In the overall patient cohort, LTFU was significantly more common among patients residing in ZIP codes with lower rates of high school completion, those with a longer interval between the emergency department visit and the scheduled follow-up appointment, and those who presented with near-normal visual acuity (close to 20/20). Among White patients, glaucomatous and retinal diagnoses were associated with lower rates of LTFU. Older age, corneal diagnoses and orbital diagnoses were associated with lower rates of LTFU among African American/Black patients. This study identified both shared and distinct factors associated with LTFU across racial groups. These findings provide a foundation for future studies investigating the mechanisms underlying follow-up adherence and may help inform efforts to improve outpatient follow-up.
Orthostatic dizziness and lightheadedness are frequent complaints in patients age 60 and above, whereas various common and uncommon etiologies need to be considered, including medication side effects, cardiovascular and metabolic causes and neurologic disorders. Autonomic dysfunction is a common etiology that warrants comprehensive medical and neurologic evaluations for identification of neurogenic orthostatic hypotension, prodromal Parkinson's disease, Lew body dementia, pure autonomic failure and others. In this article, key historical details, physical exam findings and diagnostic investigations for orthostatic dizziness are discussed. Patients' report of chronic and persistent orthostatic intolerance, even in the absence of objective orthostatic hypotension, should serve as a reliable and sufficient key feature should prompt an evaluation for autonomic and neurodegenerative disorders.
Submaximal aerobic exercise is an evidence-informed strategy for concussion management. However, its impact on the concussed pediatric brain remains poorly understood. A seminal adult study reported stability of default mode network (DMN) functional connectivity before and immediately after aerobic exercise in adults with mild traumatic brain injury. Comparable data do not exist in children, despite known developmental neurophysiological differences between children and adults. This study examined DMN network stability before and after submaximal aerobic exercise in pediatric sport-related concussion. In a controlled cohort design, 18 concussed participants (within 4 weeks of injury; 15.2 ± 1.8 years; 33% female) and 18 age- and sex-matched controls (14.5 ± 2.1 years; 50% female) completed resting-state functional magnetic resonance imaging scans pre- and post-exercise. Exercise intensity was set to 85% of the individualized symptom-limited heart rate achieved on a Buffalo Concussion Treadmill Test performed 24-48 h prior. Functional connectivity was assessed across four DMN regions of interest (posterior cingulate cortex, medial prefrontal cortex, left lateral parietal cortex, right lateral parietal cortex). Graph theory analyses conceptualized each region as a network node. Region of interest-based analyses demonstrated reduced pre- to post-exercise correlations across DMN pairs in both groups. Mean percent change was -25.8% (±12.7%) in concussion and -15.0% (±7.2%) in controls. However, no statistically significant within- or between-group correlational differences were observed, consistent with adult findings. In contrast, graph theory revealed significant post-exercise reductions in network efficiency (β = -0.17, p = 0.015), cost (β = -0.18, p = 0.014), and degree centrality (β = -0.53, p = 0.001) exclusively in the concussion group, driven primarily by the right lateral parietal cortex. While correlational analyses suggest DMN stability similar to adults, graph metrics indicate reduced network connectedness following exercise in pediatric concussion. These findings underscore the need to move beyond symptom-based frameworks and examine exercise-related neurophysiological responses in youth concussion.
This randomized clinical trial examines 1-year safety and efficacy outcomes in patients who underwent intra-arterial thrombectomy or medical management following an acute ischemic stroke with large-core infarcts.
Myocardial infarction (MI) is a major global health concern influenced by diverse risk factors. Despite growing evidence of oral-systemic connections, current MI models largely exclude oral health indicators, reflecting the longstanding separation between dental and medical paradigms. This study introduces a multidomain, interpretable machine learning framework that integrates detailed periodontal and oral hygiene variables, marking one of the first efforts to quantitatively incorporate these features into MI incidence identification. A population-based case-control dataset comprising 1,355 individuals and heterogeneous variables was used to train and evaluate seven supervised classifiers via nested cross-validation. Among them, XGBoost achieved the best performance (AUC = 0.88 ± 0.01; F1 score = 0.74 ± 0.03) and was further probability-calibrated using isotonic regression, yielding a mean Brier score of 0.14 ± 0.01 and demonstrating well-aligned predicted probabilities. SHAP values confirmed the importance of conventional cardiovascular predictors, while several periodontal indicators such as mean clinical attachment loss, plaque index, and gingival bleeding emerged among the most influential features. Sex-stratified SHAP analysis revealed sex-specific patterns in the relative impact of oral features. Additionally, individual-level waterfall plots illustrated how oral inflammation may contribute independently or in combination with conventional factors to MI incidence identification. These findings support a systems-level view of periodontitis as a modifiable, biologically relevant factor in cardiovascular health and underscore the value of considering oral-health markers within screening and management frameworks.
THUNDER (Acute Ischemic Stroke Study With the Penumbra System Including Thunderbolt Aspiration Tubing) was the first study to evaluate the safety and effectiveness of a proprietary computer assisted vacuum thrombectomy (CAVT) system including modulated aspiration (Penumbra System with Thunderbolt; Penumbra, California, USA) in patients with emergent large vessel occlusion (ELVO). THUNDER was a single arm, prospective, multicenter study with core laboratory adjudication and oversight by a Clinical Events Committee and Data Safety Monitoring Board. The primary endpoint was post-Thunderbolt successful revascularization (modified Treatment in Cerebral Infarction (mTICI) 2b-3). Secondary endpoints included first pass mTICI 2b-3, post-Thunderbolt mTICI 2c-3, time to revascularization, symptomatic intracranial hemorrhages (sICH), device/procedure related serious adverse events (SAEs) within 24 hours, 90- day modified Rankin Score (mRS) 0-2, and all cause mortality. 216 patients were enrolled across 29 US centers (mean age 64.8 years, 45.4% women, median National Institutes of Health Stroke Scale score 15.0). The predefined performance goal was met, with post-Thunderbolt mTICI 2b-3 revascularization achieved in 87.5% (95% CI 82.3% to 91.6%; P<0.001). First pass mTICI 2b-3 was 64.8%. Post-Thunderbolt mTICI 2c-3 was 70.4%. Median time to revascularization was 20 min. Post-procedure, 83.0% of visualized clots were characterized as ingested. At 90 days, mRS 0-2 was 55.4%. Device/procedure related SAEs occurred in 2.8%, sICH in 0.9%, and the rate of all cause mortality at 90 days was 11.7%. The Thunderbolt system was safe and effective for the treatment of ELVO, achieving high revascularization and clot ingestion rates, short procedure times, and low complication rates. The first pass effect rate was numerically higher than those previously reported for large bore catheters and approximated those of ultra bore/super large bore devices. ClinicalTrials.gov NCT05437055.
Multiple germline variants are associated with prostate cancer (PCa) susceptibility and aggressive features; however, their value for predicting prostate cancer-specific mortality (PCSM) at the time of diagnosis remains uncertain, particularly among men with clinically localized disease. We evaluated associations between germline risk factors and PCSM among 14,644 men with incident PCa in the UK Biobank. Associations between PCSM and reported germline risk factors, including 11 genes recommended by the National Comprehensive Cancer Network (NCCN), nine other candidate genes, two common variants [KLK3 (I179T) and HSD3B1 (1245 A > C)], and three polygenic risk scores (PRSs), were tested using Fine-Gray competing-risk models accounting for non-PCa mortality. During a median follow-up of 6.73 years after diagnosis, 1581 men (10.8%) died from PCa. PVs in three NCCN-recommended DNA damage-repair genes (BRCA2, MSH6, PALB2) were individually associated with increased PCSM and were defined as Tier-1. Aggregated PVs in seven additional NCCN-recommended DDR genes (Tier-2) and the KLK3 I179T variant were also independently associated with PCSM. In contrast, HOXB13, nine other candidate genes, HSD3B1, and all three PRSs were not associated with cumulative PCSM risk. Overall, 14.45% of men carried Tier-1 or Tier-2 PVs and/or KLK3 I179T and experienced significantly earlier PCa-specific mortality. Importantly, associations remained significant among men without metastatic disease at diagnosis. Reported inherited susceptibility to PCa does not uniformly confer risk of lethal progression. Germline PVs in NCCN-recommended DDR genes and the KLK3 I179T variant identify a subset of men at elevated risk of PCSM, including those with apparently localized disease. These findings support consideration of selected germline markers for prognostic risk stratification at diagnosis to inform individualized management decisions.
Whether breastfeeding intensity, the relative amount of breastfeeding versus formula across the first year, relates to growth trajectories among infants exposed to gestational diabetes (GDM) in utero is unknown. To identify growth trajectory patterns and associations with breastfeeding intensity among infants exposed to GDM. SWIFT Offspring cohort (2009-2011) singleton, GDM-exposed infants (n = 435) born at a Kaiser Permanente Northern California hospital. Monthly summed lactation intensity ratio (sumLIR, proportion of breastfeeding versus overall feeds over 7 days). Latent class mixed models for weight-for-age (WAZ), length-for-age (LAZ), and weight-for-length (WLZ) z-scores, and skinfold thicknesses (triceps, subscapular, and sum of skinfolds). Multinomial logistic regression related sumLIR to growth trajectories. A higher sumLIR throughout the first year was associated with lower odds of class membership in trajectories with accelerated growth patterns for WLZ from early infancy (1-mo OR: 0.11, 95% CI 0.02, 0.54) to 1 year (12-mo OR: 0.84, 95% CI 0.75, 0.95), as well as a lower likelihood of having accelerated WAZ growth after 6-months (12-mo OR: 0.91, 95% CI 0.84, 0.98), but not skinfold trajectory classes. Higher sumLIR was associated with more favourable growth trajectories, suggesting that continued breastfeeding, even when combined with infant formula, may benefit growth among GDM-exposed infants.
Fetal cardiomyopathy is a rare condition, often with an unknown cause and associated with high perinatal mortality. Recent years have seen improvement in fetal cardiac screening, genetic testing, and management. We sought to investigate genetic associations and clinical outcomes of fetal cardiomyopathy in the contemporary era. A single-arm (descriptive) retrospective cohort study of fetal cardiomyopathy cases diagnosed from January 2017 to December 2021 at 26 North American centers in the Fetal Heart Society Research Collaborative was undertaken. Cases attributable to maternal diabetes, extra-cardiac conditions, structural heart disease, or arrhythmias were excluded. Genetic testing results, extra-cardiac structural anomalies, and outcomes were collected. Logistic regression was performed to determine prenatal risk factors for death or cardiac transplantation by 1-year of age. Descriptive competing-risk analyses (cumulative incidence functions) and Kaplan-Meier survival estimates were used to describe outcomes. Multivariable logistic regression with 5 prespecified covariates was performed to identify prenatal factors associated with death or cardiac transplantation by 1-year of age. In 148 cases of fetal cardiomyopathy, 6.7% (10/148) opted for pregnancy termination, 8.6% (12/138) of continuing pregnancies experienced fetal death, and 1.4% (2/138) were lost to follow-up. Among continuing pregnancies, overall 1-year survival was 61.5% (85/138) with 1-year transplant-free survival of 50.0% (69/138). Of live births, 8.8% (11/124) received palliative care from the outset, and 21.2% (24/113) of those with intention to treat were listed for cardiac transplant, of whom 75.0% (18/24) received transplantation by age 1-year. Genetic etiologies were found in 34.0% (50/147) of the cohort, with variants of uncertain significance detected in an additional 27.2% (40/147). Fetal hydrops at the time of prenatal diagnosis (P=0.001) and a prenatal diagnosis of extracardiac structural anomalies (P≤0.001) were significantly associated with death or transplant by 1-year of age. Fetal cardiomyopathy outcomes have improved in the current era, although only half achieve 1-year cardiac transplant-free survival. Genetic testing identifies a cause in one-third of cases. Hydrops at the time of fetal cardiomyopathy diagnosis and a prenatal diagnosis of extra-cardiac structural anomalies remain important risk factors for mortality.
Significance: Sensory and subjective effects contribute to consumer response toward electronic nicotine delivery systems (ENDS). Evaluating the relative contributions of nicotine concentration, form (salt vs freebase), and carrier concentration (PG/VG ratio) is important to understanding why formulations may be more attractive. Methods: Participants were 78 adults (age ≥21) with no sensory deficits who used ENDS daily, randomized to one of two sub-studies. In Study A, 38 participants sampled tobacco-flavored e-liquids varying in PG/VG ratio (30/70, 60/40, 100/0) and nicotine concentration (0, 18, 36 mg/mL freebase). In Study B, 40 participants sampled e-liquids varying in nicotine form (salt, freebase) and concentration (0, 18, 36 mg/mL). Questionnaires assessed sensory and subjective effects. Generalized estimating equation (GEE) models examined the effects of experimental factors on these ratings. Results: Nicotine concentration was strongly related to a wide array of sensory and subjective effects measures, generally following a dose-response pattern. PG/VG showed relationships with a subset of hedonic effects independent of nicotine. There were no significant differences observed for sensory or subjective measures between salt versus freebase nicotine. Conclusions: Nicotine concentration showed consistent associations with sensory response to e-liquids when delivered in the same device. Sensory and behavioral responses to different e-liquid compositions may help contextualize ENDS usage patterns, risk perceptions, and behaviors.
Background and objectivesTo evaluate the safety and clinical efficacy of efgartigimod in adults with severe generalized myasthenia gravis (MG) exacerbations requiring ventilatory or enteral support.MethodsProspective, single-arm, open-label study conducted between November 2024 and April 2025. Sixteen consecutive adults with AChR- or MuSK-antibody-positive generalized MG requiring invasive or non-invasive ventilatory support or enteral feeding were enrolled; all met 2016 MG Guidelines criteria for impending myasthenic crisis. MGFA classification included Class IIIb (n=14), IIIa (n=1), and IVb (n=1). The primary endpoint was clinically meaningful improvement (CMI) in MG Activities of Daily Living (MG-ADL), defined as ≥2-point reduction from baseline at weeks 4 and 8.ResultsAll 16 participants (mean age 58.5±17.4 years; 8 women) completed eight weeks of follow-up. At week 8, 12 patients (75%; 95% CI 47-91%) achieved the primary endpoint. Median MG-ADL decreased from 11 (IQR 9-13) to 7 (IQR 6-9) (median change -5 points; p=0.003). Median QMG decreased from 21 (IQR 19-23) to 13 (IQR 11-16) (median change -7.5 points; p<0.001), with 56% meeting QMG-CMI by week 1. Among 12 participants receiving corticosteroids (mean starting dose 21.2 mg/day), 50% reduced or discontinued by week 8. No treatment-related serious adverse events occurred.DiscussionEfgartigimod produced rapid, clinically meaningful improvement in severe MG exacerbations without safety concerns. FcRn blockade may represent a practical alternative to plasma exchange or IVIG in acute care settings. Findings are limited by the absence of a control arm, which precludes definitive attribution of clinical improvement to efgartigimod alone.Clinical trials registrationNCT06688253.
Earlier and more frequent goals-of-care conversations (GOCCs) for patients with cancer have the potential to enhance person-centered care delivery. Structured electronic health record (EHR) functionality may support more consistent GOCCs and documentation; however, large-scale, multisite implementations remain limited. This study describes the implementation and evaluation of EHR-based goals-of-care documentation (GOCD) across 10 dedicated cancer centers participating in the Improving Goal Concordant Care (IGCC) initiative. The IGCC initiative was a multicomponent collaborative quality improvement project led by the Alliance of Dedicated Cancer Centers (ADCC) between 2020 and 2023. Participants developed a consensus definition of structured EHR GOCD to guide implementation at participating sites. Centers also used a range of enabling strategies to promote GOCD. Evaluation included process assessments and quarterly reporting on the percentage of deceased patients with at least one documented GOCC. All 10 sites implemented structured GOCD templates. Across the study period, aggregate GOCD rates improved significantly, increasing from 18% to 37% among all decedents and from 25% to 52% among inpatient decedents. However, the collaborative consensus goal of 70% was not achieved. Significant improvements in GOCD rates were observed among all decedents in 5 of 8 centers and among inpatient decedents in 6 of 9 centers. Sites that implemented clinician nudges or financial incentives achieved significantly higher final GOCD rates. This multicenter initiative demonstrated that structured EHR tools, paired with institutional engagement and behavioral strategies, can improve documentation of GOCCs in oncology. Variation in implementation across sites highlights the importance of local adaptation and sustained programmatic support in driving meaningful practice change.
UVR drives keratinocyte clonal expansion and cutaneous field damage, yet the assessment of early UV-induced field damage remains subjective and lacks an objective, non-invasive method. Reflectance confocal microscopy provides near-histologic imaging of the epidermis and may enable the detection of subclinical UV-induced changes before overt lesion development. Using SKH1 hairless mice, reflectance confocal microscopy images were analyzed during an early post-UV period at weeks 12 and 14 and a late post-UV period at weeks 16 and 18, corresponding to 6-8 and 2-4 weeks before the first visible tumor emergence, respectively. Five epidermal features significantly differentiated irradiated from control skin. Among the 5 features, atypical honeycombing and keratinocyte pleomorphism showed the strongest discriminatory value. In the early post-UV period, the expert-derived mean positivity for atypical honeycombing was 66.7-100% in irradiated skin versus 0-46.7% in control skin, while that for keratinocyte pleomorphism was 33.3-60% versus 0-13.3%, respectively. In the late post-UV period, atypical honeycombing was 46.7-100% in irradiated skin versus 0-33.3% in control skin, and keratinocyte pleomorphism was 33.3-80% versus 0-33.3%, respectively. Expert readers classified irradiated versus non-irradiated cases with 96.7% sensitivity and 90% specificity early and with 90% sensitivity and 90% specificity late. These findings support reflectance confocal microscopy as a non-invasive tool for detecting subclinical UV-related field damage.
The interest in microdosing psychedelics continues to grow within academic and recreational contexts. However, microdosing practices have changed over time, and warrants examination of use patterns within a large, global sample of consumers. The Global Psychedelic Survey 2025 (GPS 2025) was an online, anonymous, cross-sectional survey conducted from May 1-23, 2025. The survey was available in 19 languages and inquired about a wide range of topics surrounding psychedelic use. This manuscript focuses on the primary outcomes for the microdosing component of the survey, examining the substances consumed, dosing regimens employed, reasons for use, as well as the typical 'set and setting' while microdosing. In this sample, 5399 participants reported microdosing during their lifetime, of whom 69.8% (n = 3768) used a microdose within the past year. Psilocybin was the most commonly microdosed substance (n = 4377; 81.1%, 95% CI: 80.0%-82.1%), followed by LSD (n = 2136; 39.6%, 95% CI: 38.3%-40.9%). This was consistent across global regions. The 'Fadiman protocol' (i.e. one day on, two days off) was the most reported dosing regimen among regular microdosers (n = 1203; 24.3%, 95% CI: 23.1%-25.6%). While microdosing, respondents reported often spending time in nature (n = 3087; 58.9%), focusing inwards (n = 2977; 56.8%), or spending leisure time (n = 2253; 43%), demonstrating preliminary evidence supporting the integration of set and setting in the context of microdosing. This study provides a snapshot of psychedelic microdosing practices using the largest psychedelic-specific global survey to date. These findings highlight real-world practices that can guide both clinical study designs and inform harm-reduction practices in naturalistic settings.
Abatacept is approved for the treatment of moderate-severe RA, JIA and PsA in the USA and elsewhere. The purpose of this study was to estimate the incidence/birth prevalence of selected maternal and infant outcomes in pregnancies exposed to abatacept. Pregnant women exposed to any dose of abatacept from the first day of the last menstrual period to the end of the first trimester who resided in the USA or Canada were enrolled in the Organization of Teratology Information Specialists Abatacept Pregnancy Exposure Registry between 2007 and 2019. Data on exposures, outcomes and covariates were collected by maternal interviews, medical records and study-related physical examinations up to 1 year postpartum. The sample consisted of 30 abatacept-exposed pregnancies. Sixteen were enrolled prospectively and were treated for RA or PsA; 14 did not meet the prospective criteria and were enrolled in an exposure series. Of those prospectively enrolled, 2/13 (15.4%) involved an infant with a major birth defect, 2/16 (12.5%) ended in spontaneous abortion and 2/13 (15.4%) delivered preterm. In the exposure series, 5/14 livebirths (35.7%) ended with an infant with a major birth defect, 2 of which were chromosomal or genetic, and 6/14 (42.9%) delivered preterm. There were no patterns of major or minor birth defects identified in either group. In the exposure series, selected adverse outcomes were more frequent, likely due to biases that led to exclusion of these pregnancies from the prospective cohort.
Presurgical biopsy subtype guides basal cell carcinoma (BCC) risk stratification, but how well it predicts histopathology at the Mohs margin is unclear. Noninvasive imaging with reflectance confocal microscopy (RCM), line-field confocal optical coherence tomography (LC-OCT), and optical coherence tomography (OCT) may detect margin-localized tumor within imaging depth. The aim of this study was to quantify low-risk-only histopathology at stage-1 positive Mohs margins by biopsy subtype and estimate histology-based amenability to RCM, LC-OCT, and OCT. This retrospective analysis included 108 primary BCCs treated with Mohs micrographic surgery from January 2021 through November 2022. Cases with first-stage margin positivity and retrievable Mohs slides were reviewed. Potential imaging amenability was estimated as a histologic surrogate, using the depth from the granular layer to the tumor top with modality-specific thresholds of RCM ≤ 150 μm, LC-OCT ≤ 300 μm, and OCT ≤ 720 μm. Overall, 63.9% of cases showed low-risk-only histopathology at the stage-1 positive margin, whereas only 33.3% were classified as low-risk-only on biopsy. Histology-based imaging amenability was 55.6% for RCM, 65.7% for LC-OCT, and 76.9% for OCT. Among high-risk biopsy cases, estimated amenability remained substantial: 51.4%, 63.9%, and 75%, respectively. Biopsy subtype underpredicted the low-risk-only Mohs margin phenotype. Using histologic depth as a surrogate, many first-stage margin breaches were shallow enough to fall within modality-specific depth thresholds, including in high-risk biopsy tumors. As no in vivo imaging was performed, these findings estimate potential detectability and support feasibility and trial design rather than demonstrating imaging performance.