The State of Artificial Intelligence in Skin Cancer Publications.

BACKGROUND: Artificial intelligence (AI) in skin cancer is a promising research field to assist physicians and to provide support to patients remotely. Physicians' awareness to new developments in AI research is important to define the best practices and scope of integrating AI-enabled technologies within a clinical setting. OBJECTIVES: To analyze the characteristics and trends of AI skin cancer publications from dermatology journals. METHODS: AI skin cancer publications were retrieved in June 2022 from the Web of Science. Publications were screened by title, abstract, and keywords to assess eligibility. Publications were fully reviewed. Publications were divided between nonmelanoma skin cancer (NMSC), melanoma, and skin cancer studies. The primary measured outcome was the number of citations. The secondary measured outcomes were articles' general characteristics and features related to AI. RESULTS: A total of 168 articles were included: 25 on NMSC, 77 on melanoma, and 66 on skin cancer. The most common types of skin cancers were melanoma (134, 79.8%), basal cell carcinoma (61, 36.3%), and squamous cell carcinoma (45, 26.9%). All articles were published between 2000 and 2022, with 49 (29.2%) of them being published in 2021. Original studies that developed or assessed an algorithm predominantly used supervised learning (66, 97.0%) and deep neural networks (42, 67.7%). The most used imaging modalities were standard dermoscopy (76, 45.2%) and clinical images (39, 23.2%). CONCLUSIONS: Most publications focused on developing or assessing screening technologies with mainly deep neural network algorithms. This indicates the eminent need for dermatologists to label or annotate images used by novel AI systems.

Anterior segment phenotypic changes in late-onset retinal degeneration with Ser163Arg mutation in CTRP5/C1QTNF5.

PURPOSE: Late-onset retinal degeneration (L-ORD) is a rare retinal dystrophy with anterior segment (AS) abnormalities, including long anterior zonules (LAZ) and iris atrophy. This investigation evaluates AS changes in a L-ORD cohort. METHODS: Prospective, longitudinal study including L-ORD individuals (Ser163Arg) with ocular exam and standard slit-lamp photographs between 2011 and 2022. AS images were merged and assessed for LAZ number and zonule-free zone (ZFZ) radius. Further clinical findings such as iris atrophy patterns were reported descriptively. RESULTS: Twelve eyes of 6 patients (4 males, median age = 60.5 years) were included, showing a median of 160 (11-372) LAZs, mainly localized superiorly (39%) and inferiorly (24%). There was a high inter-ocular correlation (rs = 0.94, p < 0.01), no difference in LAZ count between eyes (p = 0.82), and an inverse relationship between LAZ and age (r = - 0.82; p < 0.05). The ZFZ had median 2.1 mm (1.3-5.4), with no inter-ocular difference (p = 0.31). Iris transillumination defects occurred in 11/12 eyes, with 4 major patterns identified: pupillary ruff rarefaction (10/12), patchy atrophy (6/12), notched defects (6/12), and radial streaks (2/12). In a short-term follow-up of 5.9 years, 4 eyes showed a reduction in LAZ count to median 139.5 (67-169) (p = 0.50) and a concomitant increase in ZFZ measurement to median 2.2 (1.7-2.6) (p = 0.17). CONCLUSION: This study confirms symmetric LAZs count and ZFZ in L-ORD, with ZFZ measurements smaller than in previous cohorts. A reduction in LAZs count and an increase in ZFZ with age were suggested longitudinally, yet findings need further evaluation as follow-up was limited to two cases.

Social Media in Neuro-Ophthalmology: Paradigms, Opportunities, and Strategies.

BACKGROUND: Social media (SoMe) is an integral part of life in the 21st century. Its potential for rapid dissemination and amplification of information offers opportunities for neuro-ophthalmologists to have an outsized voice to share expert-level knowledge with the public, other medical professionals, policymakers, and trainees. However, there are also potential pitfalls, because SoMe may spread incorrect or misleading information. Understanding and using SoMe enables neuro-ophthalmologists to influence and educate that would otherwise be limited by workforce shortages. EVIDENCE ACQUISITION: A PubMed search for the terms "social media" AND "neuro-ophthalmology," "social media" AND "ophthalmology," and "social media" AND "neurology" was performed. RESULTS: Seventy-two neurology articles, 70 ophthalmology articles, and 3 neuro-ophthalmology articles were analyzed. A large proportion of the articles were published in the last 3 years (2020, 2021, 2022). Most articles were analyses of SoMe content; other domains included engagement analysis such as Altmetric analysis, utilization survey, advisory opinion/commentary, literature review, and other. SoMe has been used in medicine to share and recruit for scientific research, medical education, advocacy, mentorship and medical professional networking, and branding, marketing, practice building, and influencing. The American Academy of Neurology, American Academy of Ophthalmology, and North American Neuro-Ophthalmology Society have developed guidelines on the use of SoMe. CONCLUSIONS: Neuro-ophthalmologists may benefit greatly from harnessing SoMe for the purposes of academics, advocacy, networking, and marketing. Regularly creating appropriate professional SoMe content can enable the neuro-ophthalmologist to make a global impact.

Student-led interprofessional global health course: learning impacts during a global crisis.

BACKGROUND: This study assesses the impact of the Interprofessional Global Health Course (IPGHC) on students' fundamental global health knowledge and personal viewpoints on global health domains. It explores the evolution of students' understanding of global health specifically in relation to the COVID-19 pandemic. METHODS: Ninety-nine students were selected from 123 McGill student applicants based on their motivation and commitment to take part in IPGHC's ten-week 2020 curriculum. These IPGHC students were eligible to participate in the study. The study's design is sequential explanatory mixed methods. The cross-sectional survey (quantitative phase) appraises students' global health learning outcomes using pre- and post-course surveys, with the use of 5-point Likert-scale questions. The descriptive qualitative survey (qualitative phase) further explores the impact of IPGHC on student's understanding of global health and the reflections of students on the COVID-19 pandemic after IPGHC. The post-course survey included a course evaluation for quality improvement purposes. RESULTS: Of the 99 students, 81 students across multiple undergraduate and graduate disciplines participated in the study by completing the course surveys. Mean knowledge scores of the following 11 global health topics were increased between pre- and post-course survey: Canadian Indigenous health (P < 0.001), global burden of disease (P < 0.001), global surgery (P < 0.001), infectious diseases and neglected tropical diseases (P < 0.001), refugee and immigrant health (P < 0.001), research and development of drugs (P < 0.001), role of politics and policies in global health (P = 0.02), role of technology in global health (P < 0.001), sexual violence (P < 0.001), systemic racism in healthcare (P = 0.03), and trauma in the global health context (P < 0.001). A positive change in student viewpoints was observed in response to questions regarding their perception of the importance of global health education in their own professional health care programs (P < 0.001), and their understanding of the roles and responsibilities of other healthcare professionals (P < 0.001). In the post-course survey open-ended questions, students exemplified their knowledge gained during the course to create a more informed definition of global health. Several recurring themes were identified in the student reflections on the COVID-19 pandemic, notably policy and politics, followed by access to healthcare and resources. CONCLUSION: This study emphasizes the need for interprofessional global health education at the university level and demonstrates how rapidly global health learners can apply their knowledge to evolving contexts like the COVID-19 pandemic.

Simultaneous Chromatographic Quantitation of Drug Substance and Excipients in Nanoformulations Using a Combination of Evaporative Light Scattering and Absorbance Detectors.

Nanomedicines including lipid- and polymer-based nanoparticles and polymer-drug conjugates enable targeted drug delivery for the treatment of numerous diseases. Quantitative analysis of components in nanomedicines is routinely performed to characterize the products to ensure quality and property consistency but has been mainly focused on the active pharmaceutical ingredients (APIs) in academic publications. It has been increasingly recognized that excipients in nanomedicines are critical in determining the product quality, stability, consistency, and safety. APIs are often analyzed by high-performance liquid chromatography (HPLC), and it would be convenient if the same method can be applied to excipients to robustly quantify all components in nanomedicines. Here, we report the development of a HPLC method that combined an evaporative light scattering (ELS) detector with an UV-vis detector to simultaneously analyze drugs and excipients in nanomedicines. This method was tested on diverse nanodrug delivery systems, including a niosomal nanoparticle encapsulating a phytotherapeutic, a liposome encapsulating an immune boosting agent, and a PEGylated peptide. This method can be utilized for a variety of applications, such as monitoring drug loading, studying drug release, and storage stability. The information obtained from the analyses is of importance for nanomedicine formulation development.

Gender Authorship Trends in the Ophthalmic Plastic and Reconstructive Surgery Literature.

PURPOSE: Despite increasing numbers of women oculoplastic surgeons, they remain underrepresented within the subspecialty. The purpose of this study was to analyze trends in gender authorship within the field of ophthalmic plastic and reconstructive surgery. METHODS: This retrospective observational study sampled articles published in Ophthalmic Plastic and Reconstructive Surgery (OPRS) and Orbit during the years 1985, 1995, 2005, 2015, and 2020. Data reviewed included article type, total number of authors, and the gender of each article's first and senior author. RESULTS: Nine hundred ninety-nine articles were analyzed, including 701 in OPRS and 298 in Orbit. Of 3,716 total authors, 1,151 (31%) were women, including 297 (29.7%) first authors, and 191 (21.5%) senior authors. Women authorship in OPRS in 1985 (first, 3.9%; senior, 3.3%; all, 3.2%) significantly increased by 2020 (first, 44.6%; senior, 27.9%; all, 42%). Women authorship in Orbit in 1985 (first, 0%; senior, 4.5%; all, 7.4%) also significantly increased by 2020 (first, 43.3%; senior, 34%; all, 42.9%). In a subanalysis of OPRS original investigations alone, women first authorship increased from 3.1% in 1985 to 35.8% in 2020 (p < 0.001) and women senior authorship increased from 4.3% in 1985 to 25% in 2020 (p = 0.001). In a subanalysis of Orbit original investigations alone, women first authorship increased from 0% in 1985 to 65.4% in 2020 (p < 0.001) and women senior authorship increased from 5.3% in 1985 to 42.3% in 2020 (p < 0.001). CONCLUSIONS: Despite a significant increase in women authorship over the past several decades, women remain underrepresented within the oculoplastic literature, particularly in regard to senior authorship. When considering original investigations alone, there has been a significant increase in women first and senior authorship in both OPRS and Orbit.

The ecology of the genome and the dynamics of the biological dark matter.

Transposable elements (TEs) are essential components of the eukaryotic genomes. While mostly deleterious, evidence is mounting that TEs provide the host with beneficial adaptations. How 'selfish' or 'parasitic' DNA persists until it helps species evolution is emerging as a major evolutionary puzzle, especially in asexual taxa where the lack of sex strongly impede the spread of TEs. Since occasional but unchecked TE proliferations would ultimately drive host lineages toward extinction, asexual genomes are typically predicted to be free of TEs, which contrasts with their persistence in asexual taxa. We designed innovative 'Eco-genomic' models that account for both host demography and within-host molecular mechanisms of transposition and silencing to analyze their impact on TE dynamics in asexual genome populations. We unraveled that the spread of TEs can be limited to a stable level by density-dependent purifying selection when TE copies are over-dispersed among lineages and the host demographic turn-over is fast. We also showed that TE silencing can protect host populations in two ways; by preventing TEs with weak effects to accumulate or by favoring the elimination of TEs with large effects. Our predictions may explain TE persistence in known asexual taxa that typically show fast demography and where TE copy number variation between lineages is expected. Such TE persistence in asexual taxa potentially has important implications for their evolvability and the preservation of sexual reproduction.

Impact of COVID-19 on longitudinal ophthalmology authorship gender trends.

BACKGROUND: The COVID-19 pandemic increased the gender gap in academic publishing. This study assesses COVID-19's impact on ophthalmology gender authorship distribution and compares the gender authorship proportion of COVID-19 ophthalmology-related articles to previous ophthalmology articles. METHODS: This cohort study includes authors listed in all publications related to ophthalmology in the COVID-19 Open Research Dataset and CDC COVID-19 research database. Articles from 65 ophthalmology journals from January to July 2020 were selected. All previous articles published in the same journals were extracted from PubMed. Gender-API determined authors' gender. RESULTS: Out of 119,457 COVID-19-related articles, we analyzed 528 ophthalmology-related articles written by 2518 authors. Women did not exceed 40% in any authorship positions and were most likely to be middle, first, and finally, last authors. The proportions of women in all authorship positions from the 2020 COVID-19 group (29.6% first, 31.5% middle, 22.1% last) are significantly lower compared to the predicted 2020 data points (37.4% first, 37.0% middle, 27.6% last) (p < .01). The gap between the proportion of female authors in COVID-19 ophthalmology research and the 2020 ophthalmology-predicted proportion (based on 2002-2019 data) is 6.1% for overall authors, 7.8% for first authors, and 5.5% for last and middle authors. The 2020 COVID-19 authorship group (1925 authors) was also compared to the 2019 group (33,049 authors) based on journal category (clinical/basic science research, general/subspecialty ophthalmology, journal impact factor). CONCLUSIONS: COVID-19 amplified the authorship gender gap in ophthalmology. When compared to previous years, there was a greater decrease in women's than men's academic productivity.

Determination of Patient Sentiment and Emotion in Ophthalmology: Infoveillance Tutorial on Web-Based Health Forum Discussions.

BACKGROUND: Clinical data in social media are an underused source of information with great potential to allow for a deeper understanding of patient values, attitudes, and preferences. OBJECTIVE: This tutorial aims to describe a novel, robust, and modular method for the sentiment analysis and emotion detection of free text from web-based forums and the factors to consider during its application. METHODS: We mined the discussion and user information of all posts containing search terms related to a medical subspecialty (oculoplastics) from MedHelp, the largest web-based platform for patient health forums. We used data cleaning and processing tools to define the relevant subset of results and prepare them for sentiment analysis. We executed sentiment and emotion analyses by using IBM Watson Natural Language Understanding to generate sentiment and emotion scores for the posts and their associated keywords. The keywords were aggregated using natural language processing tools. RESULTS: Overall, 39 oculoplastic-related search terms resulted in 46,381 eligible posts within 14,329 threads. Posts were written by 18,319 users (117 doctors; 18,202 patients) and included 201,611 associated keywords. Keywords that occurred ≥500 times in the corpus were used to identify the most prominent topics, including specific symptoms, medication, and complications. The sentiment and emotion scores of these keywords and eligible posts were analyzed to provide concrete examples of the potential of this methodology to allow for a better understanding of patients' attitudes. The overall sentiment score reflects a positive, neutral, or negative sentiment, whereas the emotion scores (anger, disgust, fear, joy, and sadness) represent the likelihood of the presence of the emotion. In keyword grouping analyses, medical signs, symptoms, and diseases had the lowest overall sentiment scores (-0.598). Complications were highly associated with sadness (0.485). Forum posts mentioning body parts were related to sadness (0.416) and fear (0.321). Administration was the category with the highest anger score (0.146). The top 6 forum subgroups had an overall negative sentiment score; the most negative one was the Neurology forum, with a score of -0.438. The Undiagnosed Symptoms forum had the highest sadness score (0.448). The least likely fearful posts were those from the Eye Care forum, with a score of 0.260. The overall sentiment score was much more negative before the doctor replied. The anger, disgust, fear, and sadness emotion scores decreased in likelihood, whereas joy was slightly more likely to be expressed after doctors replied. CONCLUSIONS: This report allows physicians and researchers to efficiently mine and perform sentiment analysis on social media to better understand patients' perspectives and promote patient-centric care. Important factors to be considered during its application include evaluating the scope of the search; selecting search terms and understanding their linguistic usages; and establishing selection, filtering, and processing criteria for posts and keywords tailored to the desired results.

Association between cannabis and the eyelids: A comprehensive review.

Cannabis is the most consumed illicit drug worldwide. As more countries consider bills that would legalize adult use of cannabis, health care providers, including eye care professionals (ophthalmologists, optometrists), will need to recognize ocular effects of cannabis consumption in patients. There are only 20 studies on the eyelid effects of cannabis usage as a medical treatment or a recreational drug. These include ptosis induction, an "eyelid tremor" appearance and blepharospasm attenuation. Six articles describe how adequately dosed cannabis regimens could be promising medical treatments for blepharospasm induced by psychogenic factors. Fourteen articles report eyelid tremors in intoxicated drivers and ptosis as a secondary effect in cannabinoid animal experimental models. The exact mechanism of cannabinoids connecting cannabis to the eyelids is unclear. Further studies should be conducted to better understand the cannabinoid system in relation to the eyelid and eventually develop new, effective and safe therapeutic targets derived from cannabis.

COVID-19 Recommendations From Ophthalmic and Plastic Reconstructive Surgery Societies Worldwide.

PURPOSE: The COVID-19 pandemic has brought unprecedented challenges for oculoplastic surgeons worldwide, in terms of care delivery, medical equipment and at-risk patient management. To date, there are no centralized or compiled international COVID-19 guidelines for oculoplastic surgeons. METHODS: We examined COVID-19 guidelines published by oculoplastic societies worldwide. All countries around the world were initially considered in this study, but only 9 oculoplastic societies met the inclusion criteria: (1) publicly available guidelines displayed on the oculoplastic society's website, or (2) guidelines received from the oculoplastic society after contacting them twice using the contact information on their website. RESULTS: The 9 oculoplastic societies examined include: the American Society of Ophthalmic Plastic and Reconstructive Surgery, the British Oculoplastic Surgery Society, the Canadian Society of Oculoplastic Surgery, the European Society of Ophthalmic Plastic and Reconstructive Surgery, la Sociedad Española de Cirugía Plástica Ocular y Orbitaria, la Asociación Colombiana de Cirugía Plastica Ocular, the Asia Pacific Society of Ophthalmic Plastic & Reconstructive Surgery, the Oculoplastics Association of India, and the Philippine Society of Ophthalmic Plastic and Reconstructive Surgery. They all agree that urgent procedures should not be delayed, while non-necessary procedures (including all elective clinic services) should be postponed. When adequate protective equipment is available, oculoplastic surgeons must treat urgent cases. Eight out of 9 societies have provided recommendations on personal protective equipment use in order to prevent the spread of COVID-19 and to adequately protect mucous membranes. Other recommendations provided by certain societies are related to shelter in place measures, hand hygiene and surface disinfection protocols, patient triage, and thyroid eye disease management. CONCLUSIONS: All 9 societies with published recommendations have provided valuable recommendations to their members, regarding urgency of care and infection control solutions (personal protective equipment, hand hygiene, telemedicine, and social isolation).

Prospective evaluation of finger two-point discrimination and carpal tunnel syndrome among women with breast cancer receiving adjuvant aromatase inhibitor therapy.

PURPOSE: Aromatase inhibitors (AIs) are associated with musculoskeletal symptoms and risk of developing carpal tunnel syndrome (CTS), which can impair quality of life and prompt treatment discontinuation. The incidence of CTS and clinical utility of diagnostic tests such as 2-point discrimination (2-PD) have not been prospectively examined among women receiving AIs. METHODS: Postmenopausal women with stage 0-III hormone receptor-positive breast cancer who were enrolled in a randomized clinical trial investigating adjuvant AIs (Exemestane and Letrozole Pharmacogenetics, ELPh) underwent prospective evaluation of 2-PD with the Disc-criminator™ (sliding aesthesiometer) and completed a CTS questionnaire at baseline, 3, 6, and 12 months, following initiation of AI. Changes in mean 2-PD were analyzed with multivariable mixed effects modelling. A p value < 0.05 was considered statistically significant. RESULTS: Of 100 women who underwent baseline 2-PD testing, CTS was identified by questionnaire in 11% at baseline prior to AI initiation. Prevalence of CTS at any time in the first year was 26%. A significant increase in worst 2-PD score was observed from baseline to 3 months (3.7 mm to 3.9 mm, respectively, p = 0.03) when adjusted for age, prior chemotherapy, randomized treatment assignment, and diabetes. There were no significant differences in treatment discontinuation due to CTS between the arms. CONCLUSION: For women receiving adjuvant AI, 2-PD scores were significantly worse at 3 months compared to baseline. Studies are required to assess whether change in 2-PD is an adequate objective assessment for CTS with AI therapy. Early diagnosis of CTS may expedite management, improve AI adherence, and enhance breast cancer outcomes.

Immunological and clinical effects of low-dose interleukin-2 across 11 autoimmune diseases in a single, open clinical trial.

OBJECTIVE: Regulatory T cells (Tregs) prevent autoimmunity and control inflammation. Consequently, any autoimmune or inflammatory disease reveals a Treg insufficiency. As low-dose interleukin-2 (ld-IL2) expands and activates Tregs, it has a broad therapeutic potential. AIM: We aimed to assess this potential and select diseases for further clinical development by cross-investigating the effects of ld-IL2 in a single clinical trial treating patients with 1 of 11 autoimmune diseases. METHODS: We performed a prospective, open-label, phase I-IIa study in 46 patients with a mild to moderate form of either rheumatoid arthritis, ankylosing spondylitis, systemic lupus erythematosus, psoriasis, Behcet's disease, granulomatosis with polyangiitis, Takayasu's disease, Crohn's disease, ulcerative colitis, autoimmune hepatitis and sclerosing cholangitis. They all received ld-IL2 (1 million IU/day) for 5 days, followed by fortnightly injections for 6 months. Patients were evaluated by deep immunomonitoring and clinical evaluation. RESULTS: ld-IL2 was well tolerated whatever the disease and the concomitant treatments. Thorough supervised and unsupervised immunomonitoring demonstrated specific Treg expansion and activation in all patients, without effector T cell activation. Indication of potential clinical efficacy was observed. CONCLUSION: The dose of IL-2 and treatment scheme used selectively activate and expand Tregs and are safe across different diseases and concomitant treatments. This and preliminary indications of clinical efficacy should licence the launch of phase II efficacy trial of ld-IL2 in various autoimmune and inflammatory diseases. TRIAL REGISTRATION NUMBER: NCT01988506.

A phase II study evaluating the efficacy of zoledronic acid in prevention of aromatase inhibitor-associated musculoskeletal symptoms: the ZAP trial.

PURPOSE: Aromatase inhibitor-associated musculoskeletal symptoms (AIMSS) are common adverse events of AIs often leading to drug discontinuation. We initiated a prospective clinical trial to evaluate whether bisphosphonates are associated with reduced incidence of AIMSS. METHODS: In the single-arm trial, the Zoledronic Acid Prophylaxis (ZAP) trial, we compared the incidence of AIMSS against historical controls from the Exemestane and Letrozole Pharmacogenomics (ELPh) trial. Eligible women were postmenopausal with stage 0-III breast cancer planning to receive adjuvant AIs. AIMSS was assessed using the Health Assessment Questionnaire and Visual Analog Scale over 12 months in both trials. Participants in the ZAP trial received zoledronic acid prior to initiating letrozole and after 6 months; ELPh participants included in the analysis were taking letrozole but not bisphosphonates. We analyzed patient-reported outcomes (PROs) and bone density in the ZAP trial using mixed-effects linear regression models and paired t tests, respectively. RESULTS: From 2011 to 2013, 59 postmenopausal women enrolled in ZAP trial. All 59 (100%) women received baseline and 52 (88%) received 6-month zoledronic acid, and had similar characteristics to historical controls from the ELPh trial (n = 206). Cumulatively during the first year of AI, 37 and 67% of ZAP and ELPh participants reported AIMSS (p < 0.001), respectively. Within the ZAP trial, we did not observe significant changes in other PROs; however, we report improvements in bone mineral density. CONCLUSIONS: Compared to historical controls, zoledronic acid administered concomitantly with adjuvant AIs was associated with a reduced incidence of AIMSS. A randomized controlled trial is required to confirm these findings.

A pedagogical framework for facilitating parents' learning in nurse-parent partnership.

Nursing work increasingly demands forms of expertise that complement specialist knowledge. In child and family nursing, this need arises when nurses work in partnership with parents of young children at risk. Partnership means working with parents in respectful, negotiated and empowering ways. Existing partnership literature emphasises communicative and relational skills, but this paper focuses on nurses' capacities to facilitate parents' learning. Referring to data from home visiting, day-stay and specialist toddler clinic services in Sydney, a pedagogical framework is presented. Analysis shows how nurses notice aspects of children, parents and parent-child interactions as a catalyst for building on parents' strengths, enhancing guided chance or challenging unhelpful constructs. Prior research shows the latter can be a sticking point in partnership, but this paper reveals diverse ways in which challenges are folded into learning process that position parents as agents of positive change. Noticing is dependent on embodied and communicative expertise, conceptualised in terms of sensory and reported channels. The framework offers a new view of partnership as mind-expanding for the parent and specifies the nurse's role in facilitating this process.

Effects of exemestane and letrozole therapy on plasma concentrations of estrogens in a randomized trial of postmenopausal women with breast cancer.

PURPOSE: Inter-individual differences in estrogen concentrations during treatment with aromatase inhibitors (AIs) may contribute to therapeutic response and toxicity. The aim of this study was to determine plasma concentrations of estradiol (E2), estrone (E1), and estrone sulfate (E1S) in a large cohort of AI-treated breast cancer patients. METHODS: In a randomized, multicenter trial of postmenopausal women with early-stage breast cancer starting treatment with letrozole (n = 241) or exemestane (n = 228), plasma estrogen concentrations at baseline and after 3 months were quantitated using a sensitive mass spectrometry-based assay. Concentrations and suppression below the lower limit of quantification (LLOQ) were compared between estrogens and between drugs. RESULTS: The ranges of baseline estrogen concentrations were

Accelerated kindling epileptogenesis in Tg4510 tau transgenic mice, but not in tau knockout mice.

The biologic processes underlying epileptogenesis following a brain insult are not fully understood, but several lines of evidence suggest that hyperphosphorylation of tau may be an important factor in these processes. To provide further insight into the causal relationship between tau and epileptogenesis, this study applied amygdala kindling to rTg4510 mice that, concurrent with other pathologies, overexpress phosphorylated tau, tau knockout mice, or their respective wild-type controls. Mice were electrically stimulated twice daily, 5 days per week for 3 weeks. Electroencephalography was recorded to measure the primary afterdischarge duration, and the behavioral progression of kindling-induced seizures was assessed. rTg4510 mice (n = 10) had increased primary afterdischarge durations (p < 0.001), and significantly more rapid progression of kindling (p < 0.001), compared with wild-type mice (n = 10). Tau knockout mice (n = 7), however, did not differ from their wild-type counterparts (n = 8) on any of the seizure outcomes. These results suggest that Tg4510 mice are more vulnerable to epileptogenesis, but that the presence of tau itself is not necessary for kindling epileptogenesis to occur.