Cutaneous Metastasis Following a Six-Year History of Bladder Urothelial Carcinoma in Situ: A Case Report.

Bladder cancer with cutaneous metastasis is a rare manifestation of the advanced stage of the disease. It can result from direct invasion, lymphatic or hematogenous spread, or iatrogenic implantation. We present a case of a 67-year-old patient initially diagnosed with urothelial carcinoma (UC) in situ of the bladder, who underwent transurethral resection of bladder tumor, along with induction and maintenance Bacillus Calmette-Guerin immunotherapy. Six years post-diagnosis, the patient developed multiple ulcerating fungating lesions in the right lower extremity, confirmed as metastases from UC. The patient additionally developed right foot gangrene with subsequent infection, which progressed into sepsis and caused the patient's demise.

Properties and Functional Analysis of Two Chorismate Mutases from Maritime Pine.

Through the shikimate pathway, a massive metabolic flux connects the central carbon metabolism with the synthesis of chorismate, the common precursor of the aromatic amino acids phenylalanine, tyrosine, and tryptophan, as well as other compounds, including salicylate or folate. The alternative metabolic channeling of chorismate involves a key branch-point, finely regulated by aromatic amino acid levels. Chorismate mutase catalyzes the conversion of chorismate to prephenate, a precursor of phenylalanine and tyrosine and thus a vast repertoire of fundamental derived compounds, such as flavonoids or lignin. The regulation of this enzyme has been addressed in several plant species, but no study has included conifers or other gymnosperms, despite the importance of the phenolic metabolism for these plants in processes such as lignification and wood formation. Here, we show that maritime pine (Pinus pinaster Aiton) has two genes that encode for chorismate mutase, PpCM1 and PpCM2. Our investigations reveal that these genes encode plastidial isoenzymes displaying activities enhanced by tryptophan and repressed by phenylalanine and tyrosine. Using phylogenetic studies, we have provided new insights into the possible evolutionary origin of the cytosolic chorismate mutases in angiosperms involved in the synthesis of phenylalanine outside the plastid. Studies based on different platforms of gene expression and co-expression analysis have allowed us to propose that PpCM2 plays a central role in the phenylalanine synthesis pathway associated with lignification.

Under Stress: Searching for Genes Involved in the Response of Abies pinsapo Boiss to Climate Change.

Currently, Mediterranean forests are experiencing the deleterious effects of global warming, which mainly include increased temperatures and decreased precipitation in the region. Relict Abies pinsapo fir forests, endemic in the southern Iberian Peninsula, are especially sensitive to these recent environmental disturbances, and identifying the genes involved in the response of this endangered tree species to climate-driven stresses is of paramount importance for mitigating their effects. Genomic resources for A. pinsapo allow for the analysis of candidate genes reacting to warming and aridity in their natural habitats. Several members of the complex gene families encoding late embryogenesis abundant proteins (LEAs) and heat shock proteins (HSPs) have been found to exhibit differential expression patterns between wet and dry seasons when samples from distinct geographical locations and dissimilar exposures to the effects of climate change were analyzed. The observed changes were more perceptible in the roots of trees, particularly in declining forests distributed at lower altitudes in the more vulnerable mountains. These findings align with previous studies and lay the groundwork for further research on the molecular level. Molecular and genomic approaches offer valuable insights for mitigating climate stress and safeguarding this endangered conifer.

A three-gene expression score for predicting clinical benefit to anti-PD-1 blockade in advanced renal cell carcinoma.

In the advanced renal cell carcinoma (RCC) scenario, there are no consistent biomarkers to predict the clinical benefit patients derived from immune checkpoint blockade (ICB). Taking this into consideration, herein, we conducted a retrospective study in order to develop and validate a gene expression score for predicting clinical benefit to the anti-PD-1 antibody nivolumab in the context of patients diagnosed with advanced clear cell RCC enrolled in the CheckMate-009, CheckMate-010, and CheckMate-025 clinical trials. First, a three-gene expression score (3GES) with prognostic value for overall survival integrating HMGA1, NUP62, and ARHGAP42 transcripts was developed in a cohort of patients treated with nivolumab. Its prognostic value was then validated in the TCGA-KIRC cohort. Second, the predictive value for nivolumab was confirmed in a set of patients from the CheckMate-025 phase 3 clinical trial. Lastly, we explored the correlation of our 3GES with different clinical, molecular, and immune tumor characteristics. If the results of this study are definitively validated in other retrospective and large-scale, prospective studies, the 3GES will represent a valuable tool for guiding the design of ICB-based clinical trials in the aRCC scenario in the near future.

A learning curve for first trimester anatomy ultrasound in obese patients.

OBJECTIVES: A recent randomized controlled trial of first-trimester anatomy ultrasound in obese women found some advantages to using this technique in this population, but some aspects of feasibility were not clear, such as whether first-trimester ultrasound can be brought outside of a research setting. The learning curve for first-trimester anatomy has been described in the general population, but a learning curve has not been described for this technique in obese patients. This study sought to describe a learning curve for first-trimester anatomy ultrasounds in obese patients in an operator familiar with the basics of first-trimester imaging. DESIGN: This was a secondary analysis of the EASE-O pilot randomized controlled trial (NCT04639973), which recruited 128 women with a BMI≥35 kg/m2 and randomized them into two groups based on the timing of the first evaluation of fetal anatomy, to compare the completion rate of first- and second-trimester anatomy ultrasound. PARTICIPANTS: Pregnant women with a BMI≥35 kg/m2 Setting: January 2021 and February 2022 at maternal-fetal medicine clinics in Houston, Texas Methods: This secondary analysis evaluated data on the completion rate of first-trimester scans from the parent trial. Scans were grouped into bin sizes of 3, and prop_model for R version 4.2.0 for Windows was used to generate a learning curve across the first 60 scans. RESULTS: The parent study included 60 scans performed by one imager who had previously only done first-trimester scans in lean patients for limited anatomy. The probability of a complete scan increased over 60 scans from 0.38 to 0.69; 29 scans were required to reach the final probability, after which only marginal improvement followed. LIMITATIONS: The major limitation is the inclusion of only one operator for this curve. CONCLUSIONS: For an ultrasound operator with basic familiarity in first-trimester imaging, approximately 30 scans are needed to acquire a completion rate of 70% for detailed first trimester anatomy in women with BMI ≥35 kg/m2. This can be used in education and training programs focused on imaging in the first trimester.

Recurrence of Drug-Induced Lupus Secondary to Vedolizumab Use in a Patient With Crohn's Disease.

Drug-induced lupus is an autoimmune phenomenon characterized by the development of systemic lupus erythematosus-like clinical features after drug exposure. The entity is a clinical diagnosis. Evaluation consists of recognizing systemic lupus erythematosus-like features, identifying an appropriate causative agent, observing elevations of characteristic autoantibodies, and obtaining positive response with drug discontinuation. Vedolizumab is an anti-α4ß7 antibody used in the treatment of ulcerative colitis and Crohn's disease. We report a novel case of drug-induced lupus recurrence secondary to vedolizumab use in a patient with Crohn's disease, emphasizing diagnostic evaluation, and provide a brief review of the published literature.

Detection of Constitutional Structural Variants by Optical Genome Mapping: A Multisite Study of Postnatal Samples.

Optical genome mapping is a high-resolution technology that can detect all types of structural variations in the genome. This second phase of a multisite study compares the performance of optical genome mapping and current standard-of-care methods for diagnostic testing of individuals with constitutional disorders, including neurodevelopmental impairments and congenital anomalies. Among the 627 analyses in phase 2, 405 were of retrospective samples supplied by five diagnostic centers in the United States and 94 were prospective samples collected over 18 months by two diagnostic centers (June 2021 to October 2022). Additional samples represented a family cohort to determine inheritance (n = 119) and controls (n = 9). Full concordance of results between optical genome mapping and one or more standard-of-care diagnostic tests was 98.6% (618/627), with partial concordance in an additional 1.1% (7/627).

Multiple micronutrient deficiencies as a long-term complication of bariatric surgery.

Micronutrient deficiencies may develop as a long-term complication of bariatric surgery due to alteration of gut anatomy and disruption of normal gut absorption. Inadequate repletion of essential vitamin and mineral deficiencies can lead to multisystem dysfunction. We present a case of a woman in her 50s, with a history of Roux-en-Y gastric bypass over 10 years ago, who presented with generalised weakness and a diffuse desquamating rash. A punch biopsy performed was compatible with nutritional deficiency. Labs revealed low levels of micronutrients A, B1, B6, C, E, zinc and copper. The patient received intravenous micronutrients and an oral regimen, which improved her symptoms. Unfortunately, the patient died from cardiac arrest secondary to pulmonary oedema. This report highlights the importance of high suspicion of micronutrient deficiency in patients with a history of bariatric surgery and maintaining lifelong nutritional follow-up.

Anidación de la tortuga marina Lepidochelys olivacea (Testudinata: Cheloniidae) en Campamento Tortuguero Cedeño, Honduras (2011-2021) / Nesting of olive ridley sea turtle Lepidochelys olivacea (Testudinata: Cheloniidae) in Campamento Tortuguero Cedeño, Honduras (2011-2021)

Introducción: El Campamento Tortuguero de Cedeño ha sido el sitio menos investigado del Golfo de Fonseca, donde se protege a la tortuga golfina en Honduras desde 1975. Objetivo: Evaluar la anidación de la tortuga Golfina (Lepidochelys olivacea) durante la temporada de veda entre el 2011 y 2021 en Campamento Tortuguero Cedeño, Choluteca, Honduras. Métodos: Entre 2011 a 2021, se llevó a cabo el monitoreo diario de las actividades de anidación durante la veda del 1 al 25 de septiembre. Los patrullajes se realizaron entre las 6:00-18:00 h, y las 18:00-5:00 h. Se registró el número total de tortugas que anidaban y se recogieron sus huevos, que se transportaron al criadero, donde se tabularon los resultados de las puestas y las crías. Resultados: Se registró un total 1 065 tortugas de L. olivacea, 95 051 huevos recolectados, 1 065 nidos marcados en tres playas que fueron reubicados en viveros artificiales y una eclosión exitosa de 62 747 neonatos. La playa Las Doradas fue el sitio con el mayor número de tortugas anidadoras, seguido de Los Delgaditos y por último Cedeño. El promedio de la frecuencia de anidación fue de 96 nidos. Del 2011 al 2021 el esfuerzo de recolección de los nidos aumentó en un 91.6 %, pasando de 84 a 161 nidos. El número de personas patrullando se asoció con la cantidad de nidos detectados en las playas. Conclusión: Los esfuerzos de monitoreo y conservación para la especie han indicado que ha habido un incremento en la anidación de L. olivacea en las tres playas, con un mayor incremento en Playa Las Doradas. Este escenario comprueba la funcionalidad de la veda en esta zona.

Introduction: The Cedeño Turtle Camp has been the least researched site in the Fonseca Gulf, where Olive Ridley Turtles in Honduras have been protected since 1975. Objective: To evaluate the nesting of Olive Ridley turtles (Lepidochelys olivacea) during the closed season from 2011 to 2021 in Campamento Tortuguero Cedeño, Choluteca, Honduras. Methods: From 2011 to 2021, daily monitoring of nesting activities was conducted during the closed season from the 1st to 25th of September. Patrols were conducted between 6:00-18:00 h, and 18:00-5:00 h. The total number of nesting turtles was recorded, and their eggs were collected and transported to the hatchery, where clutch and hatchling performance were tabulated. Results: A total of 1 065 L. olivacea turtles were recorded, 95 051 eggs collected, 1 065 nests marked on three beaches that were relocated in artificial hatcheries and a successful hatching of 62 747 hatchlings. Las Doradas beach was the site with the highest number of nesting turtles, followed by Los Delgaditos and lastly Cedeño. The average nesting frequency was 96 nests. From 2011 to 2021 the nest collection effort increased by 91.6 %, from 84 to 161 nests. The number of people patrolling was associated with the number of nests detected on the beaches. Conclusion: Monitoring and conservation efforts for L. olivacea in the Campamento Tortuguero Cedeño show a positive trend in nesting with a greater increase in Playa Las Doradas. This scenario proves the functionality of the closed season in this area.

Clinical presentation and neurovascular manifestations of cardiac myxomas and papillary fibroelastomas: a retrospective single-institution cohort study.

Background: Primary cardiac tumors are often benign and commonly present as cardiac myxomas (CMs) or papillary fibroelastomas (CPFEs). There is a paucity of prognostic indicators for tumor burden or potential for embolic cerebrovascular events (CVEs). This study was performed to address these gaps. Methods: Medical records at the University of Florida Health Shands Hospital between 1996 and 2021 were screened to identify patients with CMs or CPFEs. Clinical features, echocardiographic reports, and CVE outcomes were quantitatively assessed. Results: A total of 55 patients were included in the study: 28 CM (50.9%) and 27 CPFE (49.1%) patients. Baseline patient characteristics were similar among patients. The neutrophil-lymphocyte ratio was correlated (p < 0.005 in all cases) to three metrics of tumor size in both CM (r = 64-67%) and CPFE (r = 56-59%). CVEs were the presenting symptom in 30 (54.5%) patients. CVE recurrence was high; the 5-year CVE recurrence rate in patients with tumor resection was 24.0% compared to 60.0% without resection. No baseline patient characteristics or tumor features were associated with an initial presentation of CVEs compared to any other indication. Univariate analysis indicated that prolonged duration to surgical resection, left atrial enlargement, male sex, and a neutrophil-lymphocyte ratio >3.0 at the follow-up were significantly associated with 5-year CVE recurrence. Left atrial enlargement and a neutrophil-lymphocyte ratio >3.0 at the follow-up remained significantly associated with 5-year CVE recurrence in multivariate analysis. Conclusion: The neutrophil-lymphocyte ratio may prognosticate tumor size and recurrence of neurologic events. An increased risk of CVE within 5 years of mass resection is almost exclusive to patients initially presenting with CVEs.

Monitoring nutrients in plants with genetically encoded sensors: achievements and perspectives.

Understanding mechanisms of nutrient allocation in organisms requires precise knowledge of the spatiotemporal dynamics of small molecules in vivo. Genetically encoded sensors are powerful tools for studying nutrient distribution and dynamics, as they enable minimally invasive monitoring of nutrient steady-state levels in situ. Numerous types of genetically encoded sensors for nutrients have been designed and applied in mammalian cells and fungi. However, to date, their application for visualizing changing nutrient levels in planta remains limited. Systematic sensor-based approaches could provide the quantitative, kinetic information on tissue-specific, cellular, and subcellular distributions and dynamics of nutrients in situ that is needed for the development of theoretical nutrient flux models that form the basis for future crop engineering. Here, we review various approaches that can be used to measure nutrients in planta with an overview over conventional techniques, as well as genetically encoded sensors currently available for nutrient monitoring, and discuss their strengths and limitations. We provide a list of currently available sensors and summarize approaches for their application at the level of cellular compartments and organelles. When used in combination with bioassays on intact organisms and precise, yet destructive analytical methods, the spatiotemporal resolution of sensors offers the prospect of a holistic understanding of nutrient flux in plants.

Multisite Assessment of Optical Genome Mapping for Analysis of Structural Variants in Constitutional Postnatal Cases.

This study compares optical genome mapping (OGM) performed at multiple sites with current standard-of-care (SOC) methods used in clinical cytogenetics. This study included 50 negative controls and 359 samples from individuals (patients) with suspected genetic conditions referred for cytogenetic testing. OGM was performed using the Saphyr system and Bionano Access software version 1.7. Structural variants, including copy number variants, aneuploidy, and regions of homozygosity, were detected and classified according to American College of Medical Genetics and Genomics guidelines. Repeated expansions in FMR1 and contractions in facioscapulohumeral dystrophy 1 were also analyzed. OGM results were compared with SOC for technical concordance, clinical classification concordance, intrasite and intersite reproducibility, and ability to provide additional, clinically relevant information. Across five testing sites, 98.8% (404/409) of samples yielded successful OGM data for analysis and interpretation. Overall, technical concordance for OGM to detect previously reported SOC results was 99.5% (399/401). The blinded analysis and variant classification agreement between SOC and OGM was 97.6% (364/373). Replicate analysis of 130 structural variations was 100% concordant. On the basis of this demonstration of the analytic validity and clinical utility of OGM by this multisite assessment, the authors recommend this technology as an alternative to existing SOC tests for rapid detection and diagnosis in postnatal constitutional disorders.

For-profit hospitals could play a distinctive role as anchor institutions.

RATIONALE: Hospitals have a longstanding presence in United States communities and contribute to economic development and community well-being through widespread employment, purchasing and direct community engagement. Most of the data on anchor institutions to date, however, has focused on nonprofit organisations, especially nonprofit hospitals, colleges and universities. The aim of this study is to better understand if for-profit hospitals engage in explicit anchor activities, and whether these organisations adopt unique strategies in carrying out this study. METHODS: We used an inductive, qualitative approach to understand how for-profit hospitals perceive their anchoring efforts as distinct as compared to nonprofits. We conducted in-depth interviews with 23 hospital leaders, researchers and members of advocacy organisations, representing 11 different hospital organisations and 10 communities; and used thematic analysis to generate study findings. RESULTS: For-profit hospitals do see at least three primary differences that render them distinctive in their efforts to anchor themselves within their communities-namely, barriers that for-profits encounter that nonprofits may not; their emphasis on strategic and synergistic practices; and their status as hospitals that also support their communities economically as tax-paying entities. CONCLUSION: With a better understanding of their unique contributions as for-profit organisations, policymakers can identify ways to leverage these hospitals to support their communities through outreach and engagement.

Recurrent small bowel obstruction as a rare presentation of undiagnosed sarcoidosis.

Sarcoidosis is an immune-mediated inflammatory disorder with unknown aetiology that is marked by non-caseating granulomas in affected organs. Pulmonary sarcoidosis is the most common manifestation, but gastrointestinal involvement, particularly in the small bowel, is exceedingly rare. While symptom-driven treatment guidelines that are steroid based are well established for pulmonary and few extrapulmonary manifestations (ie, cardiac, neurologic, renal), gastrointestinal sarcoidosis treatment is largely extrapolation with optimal management under investigation. Additionally, few works document small bowel obstruction related to small bowel sarcoidosis. We present a case of short-interval recurrent small bowel obstruction in a man in his sixties that revealed newly diagnosed sarcoidosis with suspected small bowel involvement who never underwent steroid therapy. The patient exhibited gastrointestinal symptoms, despite asymptomatic pulmonary disease and a course of prednisone may have reduced his risk of recurrence. We also review suggested gastrointestinal sarcoidosis treatment and surveillance guidelines with focus on the small bowel.

Mobilizing Physician Assistants: Educational and Professional Outreach to Underserved Urban Communities.

There remains a dramatic underrepresentation of disadvantaged students entering physician assistant (PA) programs. To remediate this issue, healthcare professional schools have developed outreach programs to increase interest and enrollment of underrepresented minority (URM) students. There is limited research on the effectiveness of such programs in the PA education setting. We designed a program intended to stimulate URM high school students' interest in the PA profession and measure their knowledge and interest in applying to a PA program. In this pilot study, using a mixed-methods approach, we found the program increased knowledge about PA profession and education and interest in applying to PA school. However, quantitative results were not statistically significant. Findings suggest further research is needed to determine impact of outreach programs on PA schools.