Parkinsonism can be acquired by various toxic exposures, among them carbon monoxide. Since the publication of a 1972 report of Parkinsonism associated with repeated episodes of carbon monoxide exposure, the medical literature has recorded multiple cases. A distinctive bilateral change in a specific brain region, the globi pallidi, provides strong evidence for carbon monoxide-induced Parkinsonism. In addition to acute intoxication with carbon monoxide, more chronic environmental exposures may also increase the risk for Parkinsonism. Paradoxically, recent research suggests that exposure to low-dose carbon monoxide might actually have a protective effect against Parkinson disease - but this needs to be carefully and safely tested. Parkinsonism associated with carbon monoxide exposurePlain language summaryParkinsonism can be acquired by various toxic exposures, among them carbon monoxide. Since the publication of a 1972 report of Parkinsonism associated with repeated episodes of carbon monoxide exposure, the medical literature has recorded multiple cases. A distinctive bilateral change in a specific brain region, the globi pallidi, provides strong evidence for carbon monoxide-induced Parkinsonism. In addition to acute intoxication with carbon monoxide, more chronic environmental exposures may also increase the risk for Parkinsonism. Paradoxically, recent research suggests that exposure to low-dose carbon monoxide might actually have a protective effect against Parkinson disease - but this needs to be carefully and safely tested.
➢ Argentine orthopaedics was shaped by the influence of Dr. Vittorio Putti (Rizzoli Institute, Bologna, Italy). Dr. Carlos E. Ottolenghi, one of Dr. Putti's most distinguished disciples, together with Dr. José Valls, founded the Instituto de Ortopedia y Traumatología at Hospital Italiano de Buenos Aires in 1926. Prof. Ottolenghi transformed the Orthopaedic Service into a leading academic center and pioneer of subspecialization, serving as a foundational driver of orthopaedic development in Argentina and Latin America, while establishing strong international academic connections and collaborations.➢ Major milestones include the establishment of one of the earliest institutional bone banks and the performance of one of the world's first reported massive bone allograft reconstructions (1948); the performance of the first Charnley total hip replacement in the Americas (1967) and the first total knee replacement in Argentina (1970); and the early adoption of intramedullary nailing (1972), knee arthroscopy (1976), and femoral bone impaction allografting (1987). These contributions helped to define modern orthopaedic practice across Latin America and influenced global reconstructive strategies.➢ Advances such as surgical navigation (2010) and augmented reality (2025) have strengthened its role as a regional and globally connected center of excellence, particularly in musculoskeletal oncology.➢ Over the past 25 years, 180 residents and 160 fellows have been trained in our institute, and more than 500 indexed publications have been produced in the last 10 years, with alumni holding leadership roles across major orthopaedic centers worldwide, amplifying our institute's global footprint.➢ A merit-based, highly selective system based on excellence determines who becomes a staff surgeon. Currently, 85% of the actual staff surgeons completed residency training in our department, fostering a unique sense of institutional identity and perceived belonging. This experience reinforces the concept that excellence in orthopaedics transcends geographic boundaries and can emerge as a global reference from any setting committed to innovation, mentorship, and academic rigor.
Home dialysis can offer persons with kidney failure a more individualized, flexible, and independent method of dialysis compared with in-center hemodialysis (ICHD), with similar survival outcomes. Home dialysis is also generally less expensive for payers. Despite its advantages, home dialysis remains significantly underused in the United States, particularly among patients with low socioeconomic status. This article addresses current disparities in access to dialysis by examining the history and politics of home dialysis from the 1960s to the present, drawing on hundreds of archival records from dialysis organizations, for-profit dialysis companies, patient advocacy networks, public media, and congressional hearings. The enactment of the Medicare End-Stage Renal Disease (ESRD) program in 1972 was a monumental victory not just for patients receiving dialysis but also for the growing dialysis industry. In the first 4 years of the program, the rate of home dialysis among ESRD patients decreased from 43% to 20% as patients increasingly dialyzed at for-profit centers. This decline was attributed to financial disincentives, a changing patient demographic, and increased availability of ICHD. By the mid-1970s, expenses for the ESRD program had grown so high that the government turned to home dialysis as a cost-saving measure. Low-income, marginalized patients soon found themselves at the center of a debate between dialysis companies, nonprofit dialysis organizations, and government officials over who was capable of home dialysis. These debates raised questions about the ethics of for-profit medicine, patient representation in policymaking, and the potential for discrimination in incentive models. Despite implementation of financial incentives for home dialysis in 1978 and 1983, home dialysis remained underused, pointing to greater socioeconomic barriers to home dialysis access and gaps in addressing patient needs.
The history of KRT is often told as a linear narrative of technological and clinical progress, with patient experience a secondary consideration. Examining the evolution of KRT through first-person patient accounts reveals that each major innovation, while improving a life-sustaining procedure, also demanded additional new forms of courage and commitment from the patients who helped pioneer them. This is a historical narrative grounded in curated primary source patient testimonies spanning 1960-2000, the foundational period of KRT. Sources included archival documents, oral histories, published memoirs, historical journals, and transcribed video testimonies. Patient accounts revealed a continuous renegotiation of survival and a willingness to endure the unknown for the sake of scientific advancement and for the potential benefit of others. This paper follows the story of KRT from the life-saving introduction of the Scribner shunt, through the fraught empowerment of home hemodialysis, the expansion of access via Medicare, the parallel rise of peritoneal dialysis, to the hope of a successful transplant.The Scribner shunt enabled long-term dialysis but tethered patients to a relentless schedule, transforming their identity into that of permanent patient. Home dialysis offered freedom from the hospital but placed life-sustaining responsibility on families. The 1972 Medicare amendment expanded access but introduced stresses on the system. Peritoneal dialysis offered independence compatible with daily life, while transplantation promised freedom from the machine entirely, though each came with their own challenges. The patient journey has never been a linear path toward a cure, but an evolving dialogue between the body and the technology that sustains it. Throughout, pioneer patients willingly accepted unknown risks, not only for themselves but to advance science and help others. Innovation must be measured not only in years of life added, but in life added to those years, moving beyond survival toward a form of living that feels truly reclaimed.
Modifiable risk factors for the incidence of prostate cancer (PCa) have not been convincingly established. Consequently, the evidence on the relationship between alcohol consumption and the incidence of PCa has remained inconclusive. Our aim was to assess the association between alcohol consumption and the incidence of PCa. We used data from six Finnish population-based cohort studies with data collected between 1972 and 2015 that included a total of 82,570 male participants. Information on participants' alcohol consumption, BMI, height, smoking status, education, and physical activity were harmonized and categorized. Regarding alcohol consumption, the men were categorized into non-users and into light, moderate, and heavy users. Bayesian hierarchical Poisson regression was used to model the association between risk factors and PCa incidence. Alcohol consumption, among light, moderate, and heavy consumers, was associated with an increased incidence of PCa when compared to non-drinkers. The hazard ratio (HR) of PCa incidence was 1.18 (95% CI 1.02 - 1.36) for light alcohol consumers, 1.20 (95% CI 1.03 - 1.40) for moderate consumers, and 1.32 (95% CI 1.08 - 1.60) for heavy consumers. Additionally, there was some evidence of a dose-response relationship between alcohol consumption and the incidence of PCa. None of the other risk factors studied were significantly associated with the incidence of PCa. Our results provide further evidence of an association between alcohol consumption and an increased incidence of PCa. This potential relationship in the etiology of prostate cancer may offer essential information for preventive efforts.
Background/Objectives: The relationship between hyperuricemia and diabetic retinopathy (DR) remains controversial despite both conditions being associated with vascular endothelial dysfunction. This study aimed to investigate the longitudinal association between hyperuricemia and the onset and progression of DR in patients with type 2 diabetes mellitus (T2D). Methods: We conducted a retrospective cohort study using patient data from initial visits between 2005 and 2022. Patients were categorized at baseline as having no DR (NDR), simple DR (SDR). The primary endpoint was the onset of DR from NDR, and the secondary endpoint was the progression of DR from SDR. Kaplan-Meier and Cox proportional hazards analyses were employed for statistical evaluation. Results: The study included 1972 patients (1702 with NDR and 270 SDR). In the overall NDR cohort, hyperuricemia was not significantly associated with the onset or progression of DR. However, upon stratification by baseline HbA1c, hyperuricemia was significantly associated with a higher incidence of DR within the high-HbA1c subgroup (≥9%) of the NDR cohort (HR 2.40, 95% CI [1.27-4.55]). Similarly, within the SDR cohort, a Kaplan-Meier analysis demonstrated a significantly higher rate of DR progression in the hyperuricemia group, exclusively among patients with HbA1c ≥ 9% (p = 0.01). Conclusions: Hyperuricemia is independently associated with the onset and progression of DR in T2D patients with poor glycemic control While often co-occurring with other DR risk factors, hyperuricemia may serve as a potential marker for the development of retinopathy in this high-risk population.
Chemical communication in eusocial insects is crucial for colony survival and adaptation to diverse environmental conditions, contributing significantly to their evolutionary success. Pheromones, produced mainly by exocrine glands, serve as the primary means of communication among colony members. They coordinate complex social behaviors, including foraging, queen recognition, brood care, alarm signaling, and colony defense. Proper pheromone function is therefore essential for maintaining colony cohesion and efficiency. However, pathogens, particularly viruses, can influence pheromone-mediated communication through 2 main mechanisms: by altering pheromone production or by impairing pheromone perception. The impacts of viruses on exocrine glands and pheromone production have been well documented in several nonsocial insect species. Although evidence is growing for the effects of viruses on pheromone-mediated behaviors in eusocial insects, the underlying mechanisms linking viruses and pheromone signaling remain poorly understood. Here, we review current knowledge on how viral infections influence chemical communication in 2 ecologically important, eusocial insects: the honey bee (Apis mellifera Linnaeus, 1758), a nectar and pollen feeder, valued for its pollination services and honey production, and the fire ant (Solenopsis invicta Buren, 1972), an omnivore and notorious invasive pest. We further explore the ecological implications of virus-eusocial insect interactions and discuss their consequences for pollinator and pest management. Additionally, we identify knowledge gaps and highlight future research directions that could enhance our understanding of virus-pheromone dependencies. By examining these complex interactions through a chemical ecology perspective, we aim to advance the understanding of viral ecology and contribute to the development of management strategies that improve honey bee health and enable sustainable fire ant control.
Arm remodeling surgery is becoming increasingly popular due to the high impact of this anatomical unit in terms of life relationships, non-verbal language, and aesthetic concern. When referring to the post-bariatric brachioplasty (PBB), plenty of techniques have been proposed. However, PBB is challenging due to technical factors and patient's comorbidities, the evidence is limited, and there is a debate on the appropriate treatment choice. The present paper, through a systematic review, introduces a new classification system for PBB procedures, aiming to improve the management of post-bariatric patients. A systematic review was carried according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement by searching the PubMed (MEDLINE) database from December 2004 to December 2024 using the keywords ''brachioplasty OR arm contouring OR postbariatric brachioplasty OR (arm contouring AND weight loss) OR (arm contouring AND liposuction)". Original studies discussing PBB with a minimum of three clinical cases were eligible for inclusion. The final synthesis included 39 papers and 1972 patients from articles published in the last 20 years. Various PBB surgical strategies and technical measures were evidenced. The proposed classification allows a comprehensive assessment PBB techniques, possibly facilitating the treatment choice based on a patient's individual needs. Liposuction-assisted traditional PBB with the scar at the bicipital groove is effective for most post-bariatric patients. However, selected candidates may benefit from a more invasive treatment as suggested by this simple and intuitive surgical algorithm. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
Background: Basal cell carcinoma (BCC) of the skin is the most common cancer in humans, and its incidence rises annually. Despite its low death rate, BCC causes significant morbidity because of its destructive nature to local tissues. The aim of this study was to review the state of the BCC research landscape using data published in Scopus from 1972 to 2023. Methods: Using the R package Bibliometrix, we first determined authors, countries, journals, and main topics behind the advancement of BCC research. The Latent Dirichlet Allocation (LDA), a probabilistic topic algorithm, was applied to automatically discover latent (hidden) thematic structures. Additionally, the HJ-Biplot was also chosen to visualize graphical representations of multivariate scientometric and bibliometric data to improve the LDA outcome. Results: Over five decades, we discovered 32 unique themes. BCC research has shifted from studying tumor and immunohistochemically characterization, epidemiology, and surgical/histological clearance to the advancement of diagnostic and imaging techniques, like dermoscopy and reflectance confocal microscopy (RCM). Another exciting BCC research trend has been the discovery of aberrant activation within the Hedgehog signaling. Finally, patient treatment, especially surgery, radiotherapy, topical fluorouracil, and imiquimod, is an object of intense research. Conclusions: By displaying each topic as a group of related words, this in-depth exploration outlined emerging avenues in BCC evidence-based research that will benefit from the development of cutting-edge diagnostic procedures, as well as a deeper knowledge of BCC etiology and genetic underpinnings, the quality of life in BCC patients after surgery, and the application of artificial intelligence.
Waterbirds are frequently used as indicators of environmental pollution in aquatic ecosystems. However, species accumulate contaminants differently and can provide insights to diverse aspects of ecosystem health. In this study, we compared temporal and spatial trends of legacy contaminant levels (total mercury [Hg], hexachlorobenzene [HCB], p,p'-dichlorodiphenyldichloroethylene [DDE], dieldrin, Mirex, and polychlorinated biphenyls [PCBs]) in eggs of two species collected between 1972 and 2022: American Herring Gulls (Larus smithsonianus) and Great Blue Herons (Ardea herodias). We evaluated their use as environmental indicators in fluvial and marine sectors of a large drainage system with a long history of anthropogenic disturbance, the St. Lawrence River. Generalized Additive Models were applied to investigate the temporal and spatial trends due to the flexibility in modeling non-linear patterns. There were significant decreases in the concentrations of most contaminants over five decades, except Hg, in both species, and DDE and dieldrin in herons in the marine sector of the St. Lawrence River. Gulls had higher Hg and PCBs concentrations in the fluvial sector, and HCB and Mirex in the marine sector of the river, while herons only showed higher Hg concentrations in the marine sector. When comparing between sectors, PCBs were higher for both species in the fluvial sector than the marine sector. We also found higher concentrations of HCB in herons and Hg in gulls in the fluvial compared to the marine sector of the river. Declines in concentrations of legacy contaminants over the past five decades demonstrate gradual ecological recovery of the ecosystem in the St. Lawrence River, while differences in accumulation patterns between species over time reflect variations in availability and pathways of contaminants within different sectors of the St. Lawrence River.
Cardiac calcified amorphous tumours (CATs) are rare non-neoplastic intracardiac masses characterized by calcified nodules within an amorphous fibrinous matrix and may clinically mimic thrombi or cardiac neoplasms. We report two uncommon cases of right atrial CAT occurring in young women and provide a narrative review of the literature. Two patients with right atrial CAT underwent multimodality imaging evaluation, including echocardiography, computed tomography, and cardiac magnetic resonance, followed by surgical excision and histopathological examination. A narrative review of published cases identified through PubMed and Embase between 1972 and 2025 was also performed. The first patient presented with a calcified right atrial mass extending into the superior vena cava, associated with superior vena cava syndrome and autoimmune disease. The second patient, affected by end-stage renal disease on hemodialysis and thrombophilia, presented with a large calcified right atrial mass associated with a retained dialysis catheter fragment. Histopathological examination confirmed CAT in both cases. The literature review identified 112 published reports comprising 143 patients, including the two cases presented herein, highlighting frequent associations with end-stage renal disease, mitral annular calcification, and embolic complications. Cardiac CAT remains a rare and likely underrecognized entity with heterogeneous clinical presentation and significant embolic potential. Multimodality imaging is essential for diagnosis and surgical planning, while early surgical excision should be considered in symptomatic or high-risk patients.
Background/Objectives: Oral mucositis is a frequent and clinically significant acute toxicity in patients undergoing radiotherapy or chemoradiotherapy for head and neck cancer, with substantial consequences for swallowing function, nutritional status, and quality of life. Conventional clinician-reported toxicity grading may not fully capture the multidimensional burden experienced by patients. This study aimed to perform a longitudinal multidimensional assessment of treatment-related oral mucositis by evaluating the relationship between clinician-reported toxicity, objective mucosal injury, patient-reported swallowing-related quality of life, and nutritional status. Methods: In this retrospective observational study, 32 of 54 consecutively screened patients with locally advanced head and neck cancer treated with curative-intent radiotherapy, with or without concurrent chemotherapy, were included. Oral mucositis was assessed using the Common Terminology Criteria for Adverse Events (CTCAE) and the Oral Mucositis Assessment Scale (OMAS). Swallowing-related quality of life was evaluated using the MD Anderson Dysphagia Inventory (MDADI). Body weight was recorded longitudinally as an indicator of nutritional status. Correlations between OMAS scores and clinical outcome measures were analyzed at predefined timepoints using Spearman's rank correlation coefficient. Results: All patients developed treatment-related oral mucositis, with peak severity occurring during the acute treatment phase. During the acute treatment phase, OMAS scores demonstrated a moderate positive correlation with clinician-reported toxicity (CTCAE) and inverse correlations with MDADI scores. A significant inverse association between OMAS and MDADI composite score persisted at treatment completion (ρ = -0.41, p = 0.022). Body weight progressively declined during treatment, although no statistically significant correlation with OMAS severity was observed. Conclusions: A multidimensional assessment integrating clinician-reported toxicity, objective mucosal evaluation, and patient-reported functional outcomes provides a broader characterization of oral mucositis burden in patients undergoing radiotherapy-based treatment for head and neck cancer. These findings support the potential value of integrated toxicity assessment strategies to improve supportive care monitoring in clinical practice.
Penile squamous cell carcinoma (PSCC) is a rare malignancy with limited therapeutic options in advanced and recurrent diseases. Advanced PSCC is typically managed with multimodal therapy, including neoadjuvant chemotherapy or chemoradiation followed by surgery; however, durable responses remain uncommon, and outcomes after recurrence are poor. Cancer vaccines represent a promising immunotherapeutic strategy, as these treatments induce tumor-specific immunity and heightened immune surveillance against penile cancer cells. While therapeutic cancer vaccines have not yet demonstrated consistent clinical efficacy as monotherapy in PSCC, their integration with complementary immune-modulating approaches, particularly immune checkpoint blockade, represents a rational strategy to enhance antitumor immunity. This review summarizes the rationale for vaccine development in PSCC, with emphasis on HPV-derived antigens, neoantigens, and emerging tumor-associated targets. We examine major vaccine platforms, including viral-vector, peptide-based, nucleic acid, and dendritic cell-based approaches. We also discuss how spatial transcriptomics, single-cell RNA sequencing, artificial intelligence-assisted antigen prediction, and nanotechnology-enhanced delivery systems may support future personalized vaccine development. Overall, therapeutic vaccines remain investigational in PSCC but may become relevant within biomarker-driven, combination-based immunotherapy strategies.
Neurofibromatosis type 1 (NF1) is a genetic disorder occasionally associated with vascular abnormalities, including arterial fragility and spontaneous rupture. Cervical hemorrhage related to NF1 is rare, yet potentially life-threatening, and its management presents significant challenges. Here, the authors report a rare case of NF1 complicated by recurrent spontaneous cervical hemorrhage requiring repeated endovascular embolization. A 67-year-old man with NF1 presented with acute cervical swelling without a history of trauma. CT revealed a large cervical hematoma causing tracheal deviation, and CT angiography showed active extravasation from a branch of the thyrocervical artery. Emergency endovascular embolization using n-butyl-2-cyanoacrylate achieved hemostasis. The following day, recurrent hemorrhage developed from branches of the transverse cervical and internal thoracic arteries, necessitating repeat endovascular embolization. After the second intervention, no further bleeding occurred, and the patient recovered with supportive care. In patients with NF1, cervical hemorrhage may recur early from a vascular territory distinct from the initially treated lesion. Even after a technically successful embolization, close early surveillance is required. https://thejns.org/doi/10.3171/CASE26354.
Human papillomavirus (HPV) infection is the most common sexually transmitted viral infection, strongly associated with chronic inflammation and cervical cancer progression in women. Persistent HPV infection leads to an inflammatory microenvironment that promotes epithelial dysplasia and immune evasion. Exosomes derived from mesenchymal stem cells (MSC-exosomes) have emerged as promising immunomodulatory and anti-inflammatory agents. This review examines current evidence on the interaction between HPV-induced inflammation and exosomal signaling, with a particular focus on the therapeutic potential of MSC-exosomes. We discuss their roles in immune regulation, miRNA delivery, suppression of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling, and epithelial regeneration. This anti-inflammatory effect may also impair local immune surveillance, potentially enabling viral persistence and progression to malignancy. In this narrative review, We reviewed PubMed, Scopus, and Web of Science articles published up to 2024 on MSC-exosome interactions with immune regulation in HPV-related diseases. Evidence suggests that while the anti-inflammatory effects of MSC-exosomes may help control HPV-associated inflammation, they can also impair local immune surveillance, potentially facilitating viral persistence and progression toward malignancy. This dual activity positions MSC-exosomes as a double-edged sword in the context of HPV pathogenesis. A deeper understanding of this paradox is essential for designing safer, context-specific MSC-based therapies that balance anti-inflammatory benefits with effective antiviral immune responses. Although direct studies on MSC-exosomes in HPV infections are limited, existing models suggest that they have the capacity to attenuate inflammation and restore cervical tissue homeostasis. This article also highlights knowledge gaps and future research directions necessary to develop MSC-exosome-based therapies for HPV-related cervical diseases.
The global decline of coral reefs has led to the emergence of novel communities, including macroalgal-dominated states, that can be both prevalent and persistent, making understanding the dynamics of these emergent communities vital. In the South Pacific, emergent stands of Turbinaria ornata, a secondary foundation species, create an associational refuge that protects understory algae from herbivory. Our objective was to utilize a trait-based framework to examine intraspecific trait variation of T. ornata individuals and to explore if this variation differs across life stage and with position within a canopy-forming stand. We compared four functional traits related to the ecological strategies of resistance to herbivory and physical disturbance of large and recruit T. ornata thalli. We collected individuals in two community contexts-both within and at the edge of stands (n = 22 per treatment, N = 88). Trait distributions varied significantly with life stage but not with community context. Small recruits were less tough, less strong, and less compact than larger canopy-forming thalli, indicating higher vulnerability to herbivory and physical disturbance. Our findings demonstrate that the associational refuge provided by large, canopy-forming individuals is likely crucial for the protection of recruits and, therefore, the persistence of the stand. This refuge may ultimately contribute to the expansion and stability of this emerging secondary foundation species.
Background: Stigma toward people with mental illness remains a major barrier to quality care, persisting even among mental health professionals. This study evaluated the effectiveness and feasibility of a structured anti-stigma intervention for psychiatry trainees. Methods: Outcomes were assessed at baseline, post-intervention, and 3-month follow-up using a knowledge quiz, the Attitudes to Addressing Stigma and Discrimination Scale (ASTAD), and an Objective Structured Clinical Examination (OSCE). Feasibility outcomes were also evaluated. Results: Significant improvements were observed across all measures immediately after training, with medium to large effect sizes. Knowledge scores increased post-intervention (+6.68; 95% CI 5.86-7.50) and remained significantly higher at follow-up (+6; 95% CI 4.99-7.01). Total ASTAD scores improved post-intervention (+5; 95% CI 3.26-6.74) but did not maintain at follow-up. OSCE scores increased by 0.95 points (95% CI 0.62-1.28) post-training. The intervention reached 40% of eligible trainees, with high satisfaction and perceived relevance to clinical practice. Participants reported increased awareness of stigma, improved communication skills, and greater confidence in addressing stigma in patient interactions. Experiential learning methods, including role-play and case discussions, were identified as the most impactful components. Barriers to participation included workload, scheduling constraints, and limited institutional support. Participants recommended integrating the intervention into formal training curricula. Conclusions: The intervention was feasible, acceptable, and effective in improving stigma-related knowledge, attitudes, and clinical skills among psychiatry trainees. While knowledge gains were sustained, attitudinal and behavioral changes were only partially maintained, highlighting the need for longitudinal integration and ongoing reinforcement.
Although transcatheter aortic valve replacement (TAVR) can improve cerebral blood flow (CBF) in patients with aortic stenosis (AS), the effect of pre-TAVR flow rate on post-TAVR flow rate increase is unclear. We aimed to evaluate blood flow changes before and after TAVR in the ascending aorta (AAo) and brachiocephalic artery (BCA) using four-dimensional flow cardiovascular magnetic resonance (4D flow CMR) and assess whether the post-TAVR flow response depends on the pre-TAVR flow rate. This prospective study included patients who underwent TAVR for AS at our institution between January 2022 and December 2023 and who underwent 4D flow CMR before and after TAVR. Patients were divided into two groups, normal-flow (NF) and low-flow (LF) groups, using a cutoff value of 35mL/beat/m2 for the ratio of pre-TAVR AAo flow rate per beat to body surface area. Flow rates in the AAo and BCA were analyzed. Sixty-one patients were enrolled. The median age was 84 (82-87) years, and twenty-three patients (38%) were men. The net flow rates in the AAo and BCA increased after TAVR, but the changes were not statistically significant (AAo, 3206 (2499-3975) mL/min vs. 3591 (2880-4419) mL/min, p = 0.23; BCA, 435 (302-560) mL/min vs. 512 (377-666) mL/min, p = 0.06). In the analysis of the NF and LF groups, the LF group demonstrated significant increases in net flow after TAVR (AAo, 2598 (1972-3079) vs. 3468 (2900-4131) mL/min, p < 0.001; BCA, 365 (230-529) vs. 522 (377-659) mL/min, p = 0.006). 4D flow CMR revealed that TAVR significantly increased the AAo and BCA flow rates in patients with LF AS. (274 words / 350 limit).
This project elucidates the pivotal scientific discoveries that culminated in the isolation of luteinizing hormone-releasing hormone (LH-RH). It details the contributions of scientists Andrew Schally and Roger Guillemin, whose competitive biochemical research led to the Nobel Prize in 1977. This project entails a comprehensive review of the pivotal scientific developments that culminated in the discovery of LHRH, examined through the historical lens. The sources included peer-reviewed articles, Nobel lectures, and oral history transcripts. G.W. Harris first showed the anterior pituitary's regulation by the hypothalamus in 1937, establishing the principles for Schally and Guillemin. Schally and Guillemin independently isolated TRF in 1969, requiring 160,000 porcine hypothalami for purification. Both then pursued LHRH, isolating it independently in 1971 using 240,000 porcine brains and developing advanced biochemical techniques. These methods have enabled LHRH analog synthesis for prostate cancer research. In 1971, Schally demonstrated that LHRH could suppress gonadotropin secretion. Synthetic LHRH infusion in monkeys showed LHRH's ability to desensitize pituitary GnRH receptors. This discovery enabled the use of LHRH analog treatments for hormone-sensitive conditions. Schally conducted the first clinical trials in Mexico in 1972 and organized the first LHRH agonist study for prostate cancer, which was published in 1982. The discovery of LHRH represents a landmark convergence of evolving physiological concepts, rigorous biochemical innovation, and impactful clinical translation, leading to the Nobel Prize. The rivalry between Schally and Guillemin led to foundational discoveries that transformed the management of androgen-dependent malignancies.
Only a small fraction of the global fungal diversity is described, and a large number of fungal sequences from environmental DNA (eDNA) lack relevant reference sequences for taxonomic identification in metabarcoding studies. Among these are several deeply divergent fungal lineages, hypothesized to be class- and order-level lineages, currently known only by eDNA sequences. Here, we formally describe the first representative of one such lineage, previously referred to as Clade GS25, now captured in culture. We use a phylogenomic approach to test the phylogenetic placement and taxonomic rank hypothesized for this lineage and present the formally described Semicentenialea rex sp. nov. as the first known species in the novel class Semicentenialomycetes (Pucciniomycotina, Basidiomycota). Semicentenialea rex sp. nov. was isolated from pine roots taken from a podzol soil profile in a pine forest in central Sweden and shows an affinity to mineral soil horizons in this habitat. The same species was isolated independently from pine roots collected in central Finland. Additionally, we provide the first phylogenomic resolution of Pucciniomycotina, using reference genomes from all described classes with the exception of Cryptomycocolacomycetes. In addition to expanding our knowledge about the diversity of Pucciniomycotina, our study highlights the importance of continued culturing efforts in combination with eDNA studies to uncover hidden fungal diversity. Furthermore, our data provide insights into the strengths and limitations associated with amplicon sequence variants, different similarity cut-offs, and genome-derived ribosomal operons.