The first complete T2T Assemblies of Cattle and Sheep Y-Chromosomes uncover remarkable divergence in structure and gene content.

Reference genomes of cattle and sheep have lacked contiguous assemblies of the sex-determining Y chromosome. We assembled complete and gapless telomere to telomere (T2T) Y chromosomes for these species. The pseudo-autosomal regions were similar in length, but the total chromosome size was substantially different, with the cattle Y more than twice the length of the sheep Y. The length disparity was accounted for by expanded ampliconic region in cattle. The genic amplification in cattle contrasts with pseudogenization in sheep suggesting opposite evolutionary mechanisms since their divergence 18MYA. The centromeres also differed dramatically despite the close relationship between these species at the overall genome sequence level. These Y chromosome have been added to the current reference assemblies in GenBank opening new opportunities for the study of evolution and variation while supporting efforts to improve sustainability in these important livestock species that generally use sire-driven genetic improvement strategies.

Developmental milestones in captive Galago moholi.

Systems of the body develop in a modular manner. For example, neural development in primates is generally rapid, whereas dental development varies much more. In the present study, we examined development of the skull, teeth, and postcrania in a highly specialized leaping primate, Galago moholi. Eighteen specimens ranging from birth to adult were studied. Bones, teeth, and the cranial cavity (i.e., endocast) were reconstructed with Amira software based on microCT cross-referenced to histology. Amira was also used to compute endocast volume (as a proxy for brain size). Reconstructions of the wrist and ankle show that ossification is complete at 1 month postnatally, consistent with the onset of leaping locomotion in this species. Endocranial volume is less than 50% of adult volume at birth, ~80% by 1 month, and has reached adult volume by 2 months postnatal age. Full deciduous dentition eruption occurs by 2 weeks, and the young are known to begin capturing and consuming arthropods on their own by 4 weeks, contemporaneous with the timing of bone and ankle ossification that accompanies successful hunting. The modular pattern of development of body systems in Galago moholi provides an interesting view of a "race" to adult morphology for some joints that are critical for specialized leaping and clinging, rapid crown mineralization to begin a transitional diet, but perhaps more prolonged reliance on nursing to support brain growth.

Engineered IgM and IgG cleaving enzymes for mitigating antibody neutralization and complement activation in AAV gene transfer.

Systemic dosing of adeno-associated viral (AAV) vectors poses potential risk of adverse side-effects including complement activation triggered by anti-capsid immunity. Due to the multifactorial nature of toxicities observed in this setting, a wide spectrum of immune modulatory regimens (IMR) are being investigated in the clinic. Here, we discover an IgM cleaving enzyme (IceM) that degrades human IgM, a key trigger in the anti-AAV immune cascade. We then engineer a fusion enzyme (IceMG) with dual proteolytic activity against human IgM and IgG. IceMG cleaves B cell surface antigen receptors (BCR) and inactivates phospholipase gamma signaling in vitro. Importantly, IceMG is more effective at inhibiting complement activation compared to an IgG cleaving enzyme alone. Upon IV dosing, IceMG rapidly and reversibly clears circulating IgM and IgG in macaques. Antisera from these animals treated with IceMG shows decreased ability to neutralize AAV and activate complement. Consistently, pre-conditioning with IceMG restores AAV transduction in mice passively immunized with human antisera. Thus, IgM cleaving enzymes show promise in simultaneously addressing multiple aspects of anti-AAV immunity mediated by B cells, circulating antibodies and complement. These studies have implications for improving safety of AAV gene therapies and possibly broader applications including organ transplantation and autoimmune diseases.

Introgression and disruption of migration routes have shaped the genetic integrity of wildebeest populations.

The blue wildebeest (Connochaetes taurinus) is a keystone species in savanna ecosystems from southern to eastern Africa, and is well known for its spectacular migrations and locally extreme abundance. In contrast, the black wildebeest (C. gnou) is endemic to southern Africa, barely escaped extinction in the 1900s and is feared to be in danger of genetic swamping from the blue wildebeest. Despite the ecological importance of the wildebeest, there is a lack of understanding of how its unique migratory ecology has affected its gene flow, genetic structure and phylogeography. Here, we analyze whole genomes from 121 blue and 22 black wildebeest across the genus' range. We find discrete genetic structure consistent with the morphologically defined subspecies. Unexpectedly, our analyses reveal no signs of recent interspecific admixture, but rather a late Pleistocene introgression of black wildebeest into the southern blue wildebeest populations. Finally, we find that migratory blue wildebeest populations exhibit a combination of long-range panmixia, higher genetic diversity and lower inbreeding levels compared to neighboring populations whose migration has recently been disrupted. These findings provide crucial insights into the evolutionary history of the wildebeest, and tangible genetic evidence for the negative effects of anthropogenic activities on highly migratory ungulates.

Pilot trial of perampanel on peritumoral hyperexcitability and clinical outcomes in newly diagnosed high-grade glioma.

Background: Glutamatergic neuron-glioma synaptogenesis and peritumoral hyperexcitability promote glioma growth in a positive feedback loop. The objective of this study was to evaluate the feasibility and estimated effect sizes of the AMPA-R antagonist, perampanel, on intraoperative electrophysiologic hyperexcitability and clinical outcomes. Methods: An open-label trial was performed comparing perampanel to standard of care (SOC) in patients undergoing resection of newly-diagnosed radiologic high-grade glioma. Perampanel was administered as a pre-operative loading dose followed by maintenance therapy until progressive disease or up to 12-months. SOC treatment involved levetiracetam for 7-days or as clinically indicated. The primary outcome of hyperexcitability was defined by intra-operative electrocorticography high frequency oscillation (HFO) rates. Seizure-freedom and overall survival (OS) were estimated by the Kaplan-Meier method. Tissue concentrations of perampanel, levetiracetam, and metabolites were measured by mass spectrometry. Results: HFO rates were similar between perampanel-treated and SOC cohorts. The trial was terminated early after interim analysis for futility, and outcomes assessed in 11 patients (7 perampanel-treated, 4 SOC). Over a median 281 days of post-enrollment follow-up, 27% of patients had seizures, including 14% treated with perampanel and 50% treated with SOC. OS in perampanel-treated patients was similar to a glioblastoma reference cohort (p=0.81). Glutamate concentrations in surface biopsies were positively correlated with HFO rates in adjacent electrode contacts and were not significantly associated with treatment assignment or drug concentrations. Conclusions: A peri-operative loading regimen of perampanel was safe and well-tolerated, with similar peritumoral hyperexcitability as in levetiracetam-treated patients. Maintenance anti-glutamatergic therapy was not observed to impact survival outcomes.

Chromosome-scale Genome Assembly of the Rough Periwinkle Littorina saxatilis.

The intertidal gastropod Littorina saxatilis is a model system to study speciation and local adaptation. The repeated occurrence of distinct ecotypes showing different levels of genetic divergence makes L. saxatilis particularly suited to study different stages of the speciation continuum in the same lineage. A major finding is the presence of several large chromosomal inversions associated with the divergence of ecotypes and, specifically, the species offers a system to study the role of inversions in this divergence. The genome of L. saxatilis is 1.35 Gb and composed of 17 chromosomes. The first reference genome of the species was assembled using Illumina data, was highly fragmented (N50 of 44 kb), and was quite incomplete, with a BUSCO completeness of 80.1% on the Metazoan dataset. A linkage map of one full-sibling family enabled the placement of 587 Mbp of the genome into 17 linkage groups corresponding to the haploid number of chromosomes, but the fragmented nature of this reference genome limited the understanding of the interplay between divergent selection and gene flow during ecotype formation. Here, we present a newly generated reference genome that is highly contiguous, with a N50 of 67 Mb and 90.4% of the total assembly length placed in 17 super-scaffolds. It is also highly complete with a BUSCO completeness of 94.1% of the Metazoa dataset. This new reference will allow for investigations into the genomic regions implicated in ecotype formation as well as better characterization of the inversions and their role in speciation.

Enhanced bovine genome annotation through integration of transcriptomics and epi-transcriptomics datasets facilitates genomic biology.

BACKGROUND: The accurate identification of the functional elements in the bovine genome is a fundamental requirement for high-quality analysis of data informing both genome biology and genomic selection. Functional annotation of the bovine genome was performed to identify a more complete catalog of transcript isoforms across bovine tissues. RESULTS: A total of 160,820 unique transcripts (50% protein coding) representing 34,882 unique genes (60% protein coding) were identified across tissues. Among them, 118,563 transcripts (73% of the total) were structurally validated by independent datasets (PacBio isoform sequencing data, Oxford Nanopore Technologies sequencing data, de novo assembled transcripts from RNA sequencing data) and comparison with Ensembl and NCBI gene sets. In addition, all transcripts were supported by extensive data from different technologies such as whole transcriptome termini site sequencing, RNA Annotation and Mapping of Promoters for the Analysis of Gene Expression, chromatin immunoprecipitation sequencing, and assay for transposase-accessible chromatin using sequencing. A large proportion of identified transcripts (69%) were unannotated, of which 86% were produced by annotated genes and 14% by unannotated genes. A median of two 5' untranslated regions were expressed per gene. Around 50% of protein-coding genes in each tissue were bifunctional and transcribed both coding and noncoding isoforms. Furthermore, we identified 3,744 genes that functioned as noncoding genes in fetal tissues but as protein-coding genes in adult tissues. Our new bovine genome annotation extended more than 11,000 annotated gene borders compared to Ensembl or NCBI annotations. The resulting bovine transcriptome was integrated with publicly available quantitative trait loci data to study tissue-tissue interconnection involved in different traits and construct the first bovine trait similarity network. CONCLUSIONS: These validated results show significant improvement over current bovine genome annotations.

Predictors of Sinonasal Improvement After Highly Effective Modulator Therapy in Adults with Cystic Fibrosis.

OBJECTIVES: The 22-question SinoNasal Outcome Test (SNOT-22) assesses chronic rhinosinusitis (CRS) severity. We aimed to identify predictors of SNOT-22 score improvement following highly effective modulator therapy (HEMT) initiation and to corroborate the SNOT-22 minimal clinically important difference (MCID) in adults with cystic fibrosis (CF). METHODS: Prospective observational data was pooled from four studies across 10 US centers investigating people with CF (PwCF) and CRS. Three studies evaluated HEMT's impact on CRS. For participants enrolled prior to HEMT initiation, SNOT-22 scores were obtained at baseline and after 3-6 months of HEMT. Multivariate regression identified predictors of improvement. Cronbach's alpha and four distribution-based methods were used to assess internal consistency and calculate the MCID of the SNOT-22. RESULTS: A total of 184 PwCF participated with mean baseline SNOT-22 scores ranging from 18.1 to 56.7. Cronbach's alpha was ≥0.90 across sites. Participants at sites with pre- and post-HEMT data reported improvement in SNOT-22 scores after initiating HEMT (all p < 0.05). Worse baseline SNOT-22 score (odds ratio (OR): 1.05, p < 0.001, 95% CI: 1.02-1.08), F508del homozygosity (OR: 4.30, p = 0.040, 95% CI: 1.14-18.99), and absence of prior modulator therapy (OR: 4.99, p = 0.017, 95% CI: 1.39-20.11) were associated with greater SNOT-22 improvement. The mean MCID calculated via distribution-based methods was 8.5. CONCLUSION: Worse baseline sinonasal symptoms, F508del homozygosity, and absence of prior modulator therapy predicted greater improvement after HEMT initiation. The mean MCID for SNOT-22 in PwCF is 8.5 points, similar to non-CF individuals with CRS, and provides a threshold specifically for PwCF. The SNOT-22 has strong internal consistency in PwCF. LEVEL OF EVIDENCE: 3 Laryngoscope, 2024.

The Impact of Acute Peri-operative Particulate Matter Exposure on Endoscopic Sinus Surgery Outcomes: A Preliminary Multi-site Investigation.

BACKGROUND: Environmental exposures have been postulated to play an important role in the pathophysiology of chronic rhinosinusitis (CRS). Particulate matter (PM) is one of the most widely studied ambient air pollutants, but its peri-operative impact on CRS is unknown. OBJECTIVE: To determine the effect of acute, peri-operative PM exposure on outcomes after endoscopic sinus surgery (ESS). METHODS: Participants with CRS who self-selected ESS were prospectively enrolled. The 22-item SinoNasal Outcome Test (SNOT-22) and Medical Outcomes Study Questionnaire Short-Form 6-D (SF-6D) health utility values scores were recorded. Using residence zip codes, a secondary analysis of patient exposure to PM <2.5 µm and <10 µm (PM2.5 and PM10, respectively) was performed for the month of surgery utilizing data from Environmental Protection Agency air quality monitors. Spearman's correlation coefficients (ρ), 95% confidence intervals (CIs), and effect estimates (ß) were used to determine the magnitudes of association. Simple, multivariate regression analysis was also completed. RESULTS: One hundred and seven patients from four geographically unique institutions across the US were enrolled with a follow-up of 6 months. Patients with higher peri-operative PM2.5 exposure had less improvement in their SNOT-22 scores after ESS compared to those with less exposure using both univariate analysis (ρ = 0.26, 95% CI: 0.08, 0.43; P = .01) and after covariate adjustment with multivariate analysis (B = 1.06, 95% CI: 0.001, 2.14, P = .05). Similar associations were not found with SF-6D outcomes or with PM10 as an exposure of interest. No significant correlations were found between peri-operative PM levels and Lund-Kennedy endoscopy scores post-operatively. CONCLUSION: Preliminary data from this pilot study reveal that PM exposure at the time of ESS may negatively associate with post-operative improvement in sinonasal quality-of-life. Larger, population-based studies with more standardized PM exposure windows are needed to confirm the clinical significance of the present findings.

Utilization of RNA sequencing to investigate olfactory dysfunction in chronic rhinosinusitis without nasal polyps: A pilot study.

Objectives: Prior research on olfactory dysfunction in chronic rhinosinusitis (CRS) has focused on patients with polyps and suggests that direct inflammation of the olfactory cleft mucosa plays a contributory role. The purpose of this study was to evaluate gene expression in superior turbinate mucosal specimens, comparing normosmic and dysosmic CRS patients without polyps (CRSsNP). Methods: Tissue samples were obtained from the superior turbinates of patients with CRSsNP at the time of endoscopic sinus surgery. Samples subsequently underwent RNA sequencing and functional analysis to investigate biological pathways associated with differentially expressed genes between dysosmic (n = 7) and normosmic (n = 4) patients. Results: Differential gene expression analysis comparing dysosmic and normosmic CRSsNP patients showed upregulation of 563 genes and downregulation of 327 genes. Using stringent criteria for multiple comparisons, one upregulated gene (Immediate Early Response 3 [IER3]) had an false discovery rate (FDR) correction adjusted P value considered statistically significant (P < 0.001, fold change 2.69). Reactome functional analysis revealed eight biological pathways significantly different between dysosmic and normosmic patients (P < 0.05, FDR correction) including IL-4 and IL-13 signaling, IL-10 signaling, and rhodopsin-like receptors. Conclusions: RNA sequencing of the superior turbinates in patients with CRSsNP can provide valuable information regarding biological pathways and genes involved in olfactory dysfunction. This study supports literature suggesting that Type 2 inflammation may play a role in olfactory dysfunction in at least some patients with CRSsNP. This study also prompts questions regarding the role of IL-10, rhodopsin-like receptors, and IER3 in the pathogenesis of olfactory dysfunction.

Taste dysfunction after endoscopic endonasal resection of olfactory groove meningioma: Case series and review of the literature.

PURPOSE: The incidence of ageusia and dysgeusia after endoscopic endonasal (EEA) resection of olfactory groove meningioma (OGM) is not well established despite recognized impairment in olfactory function. METHODS: We retrospectively administered a validated taste and smell survey to patients undergoing EEA for resection of OGM at two institutions. Demographics and clinical characteristics were collected and survey responses were analyzed. RESULTS: Twelve patients completed the survey. The median time from surgery was 24 months. The average total complaint score was 5.5 out of 16 [0-13]. All patients reported a change in sense of smell while only 42 % reported a change in sense of taste. Taste changes did not consistently associate with laterality or size of the neoplasm. Significant heterogeneity existed when rating severity of symptoms. CONCLUSIONS: To our knowledge this is the first case series examining taste changes after EEA resection of OGM. Despite universal olfactory dysfunction, only a minority of patients reported a change in their sense of taste. Our findings may improve patient counseling and expectations after surgery.

Cardiovascular risk, social vigilance, and stress profiles of male law enforcement officers versus civilians.

This study examined the cardiovascular disease (CVD) risk profiles of male law enforcement officers (LEOs) and civilians. CVD risk profiles were based on data collected using traditional objective (e.g., resting BP, cholesterol), novel objective (e.g., ambulatory BP) and self-report measures (e.g., EMA social vigilance). A subset of male LEOs (n = 30, M age = 41.47, SD = 8.03) and male civilians (n = 120, M age = 40.73, SD = 13.52) from a larger study were included in analyses. Results indicated LEOs had significantly higher body mass index [BMI], 31.17 kg/m2 versus 28.87 kg/m2, and exhibited significantly higher trait and state social vigilance across multiple measures, whereas perceived stress was higher among civilians. Findings highlight the need for future research examining CVD risk associated with occupational health disparities, including attributes of individuals entering certain professions as well as experiential and environmental demands of the work.

Management of Post-Dural Puncture Headaches in Pediatric Patients with Epidural Blood or Saline Patch: An Educational Focused Review.

Post-dural puncture headache (PDPH) is a common adverse outcome following puncture of the dura. It can occur after inadvertent dural puncture during epidural catheter placement or following diagnostic or therapeutic LP. The incidence of PDPH in pediatric patients has been estimated at 1-15% depending on patient factors (age, gender, body mass index) and needle factors (size and needle bevel/point type). The larger the needle gauge, the higher the incidence of PDPH. Various options have been proposed to treat PDPH including observation, bed rest, hydration, caffeine, and epidural blood/saline patch. The current manuscript provides a review of the use of epidural blood/saline patch in pediatric-aged patients with PDPH.

Capsid-mediated control of adeno-associated viral transcription determines host range.

Adeno-associated virus (AAV) is a member of the genus Dependoparvovirus, which infects a wide range of vertebrate species. Here, we observe that, unlike most primate AAV isolates, avian AAV is transcriptionally silenced in human cells. By swapping the VP1 N terminus from primate AAVs (e.g., AAV8) onto non-mammalian isolates (e.g., avian AAV), we identify a minimal component of the AAV capsid that controls viral transcription and unlocks robust transduction in both human cells and mouse tissue. This effect is accompanied by increased AAV genome chromatin accessibility and altered histone methylation. Proximity ligation analysis reveals that host factors are selectively recruited by the VP1 N terminus of AAV8 but not avian AAV. Notably, these include AAV essential factors implicated in the nuclear factor κB pathway, chromatin condensation, and histone methylation. We postulate that the AAV capsid has evolved mechanisms to recruit host factors to its genome, allowing transcriptional activation in a species-specific manner.

Empty sella in somatotropic pituitary adenomas; a series of 23 cases.

Purpose: We aimed to investigate empty sella syndrome in somatotrophic pituitary adenoma for possible etiology, complications, and treatment options. Method: Among over 2,000 skull base masses that have been managed in our center since 2013, we searched for growth hormone-producing adenomas. Clinical, surgical, and imaging data were retrospectively collected from hospital records to check for sella that lacked pituitary tissue on routine imaging. Result: In 220 somatotrophic adenomas, 23 patients had an empty sella with surgical and follow-up data. The mean age of the sample was 46 years with the same male-to-female ratio. Five cases had partial empty sella and the rest were complete empty sellas. The most common simultaneous hormonal disturbance was high prolactin levels. Six had adenoma invasion into the clivus or sphenoid sinus and 10 had cavernous sinus intrusion. Peri-operative low-flow and high-flow cerebrospinal fluid (CSF) leaks were encountered in one and two patients, respectively, which were successfully sealed by abdominal fat. The majority of cases required growth hormone replacement therapy while it was controlled without any replacement therapy in nine patients. No pituitary hormonal disturbance occurred after transsphenoidal surgery except for hypothyroidism in one patient. Conclusion: An empty sella filled with fluid can be detected frequently in pituitary adenomas, especially in the setting of acromegaly. The pituitary gland may be pushed to the roof of the sella and might be visible as a narrow rim on imaging or may be detected in unusual places out of the sella. The pathophysiology behind such finding originates from soft and hard tissue changes and CSF pressure alternations during abundant growth hormone production.

Space invaders: Reassessing the histology of hyperostosis frontalis interna.

Hyperostosis frontalis interna (HFI) is a human skeletal lesion characterized by nodules of hyperplastic bone and thickening of the frontal bone's inner surface. Despite its prevalence in the general population and its long history of observation-it is one of the most frequently observed pathologies in gross anatomy laboratories-HFI's etiology and pathogenesis remain poorly understood. This is largely due to the lack of a thorough survey of its histology across the various stages of its development. Our study has three major aims: (1) assess HFI histology from incipient to advanced lesions; (2) elucidate lamellar and trabecular structure in HFI; and (3) clarify impacts/roles of the dura mater in HFI. Sections of nondecalcified bone provide evidence for two different categories of lesions: (1) stratum lesions, characterized by lamellar-based overall thickening of the internal table, and (2) eruptive lesions, characterized by nodular formations of initially lamellar bone that appear to form the bulk of bone mass in advanced stages. Sections of nondecalcified bone also suggest that for both lesion types, HFI growths begin as deposits of lamellar bone, which are later remodeled into woven bone deposits; our data do not support the hypothesis that lesions begin as a "diploization" of cortical bone as suggested by prior studies. Trichrome-stained sections provide evidence that growing lesions erode through and engulf the dura mater, effectively destroying this tissue layer as they grow laterally and inwardly. Our results indicate possible avenues of research to better understand the root causes of this disorder.

Surgical Navigation in the Anterior Skull Base Using 3-Dimensional Endoscopy and Surface Reconstruction.

Importance: Image guidance is an important adjunct for endoscopic sinus and skull base surgery. However, current systems require bulky external tracking equipment, and their use can interrupt efficient surgical workflow. Objective: To evaluate a trackerless surgical navigation system using 3-dimensional (3D) endoscopy and simultaneous localization and mapping (SLAM) algorithms in the anterior skull base. Design, Setting, and Participants: This interventional deceased donor cohort study and retrospective clinical case study was conducted at a tertiary academic medical center with human deceased donor specimens and a patient with anterior skull base pathology. Exposures: Participants underwent endoscopic endonasal transsphenoidal dissection and surface model reconstruction from stereoscopic video with registration to volumetric models segmented from computed tomography (CT) and magnetic resonance imaging. Main Outcomes and Measures: To assess the fidelity of surface model reconstruction and accuracy of surgical navigation and surface-CT model coregistration, 3 metrics were calculated: reconstruction error, registration error, and localization error. Results: In deceased donor models (n = 9), high-fidelity surface models of the posterior wall of the sphenoid sinus were reconstructed from stereoscopic video and coregistered to corresponding volumetric CT models. The mean (SD; range) reconstruction, registration, and localization errors were 0.60 (0.24; 0.36-0.93), 1.11 (0.49; 0.71-1.56) and 1.01 (0.17; 0.78-1.25) mm, respectively. In a clinical case study of a patient who underwent a 3D endoscopic endonasal transsphenoidal resection of a tubercular meningioma, a high-fidelity surface model of the posterior wall of the sphenoid was reconstructed from intraoperative stereoscopic video and coregistered to a volumetric preoperative fused CT magnetic resonance imaging model with a root-mean-square error of 1.38 mm. Conclusions and Relevance: The results of this study suggest that SLAM algorithm-based endoscopic endonasal surgery navigation is a novel, accurate, and trackerless approach to surgical navigation that uses 3D endoscopy and SLAM-based algorithms in lieu of conventional optical or electromagnetic tracking. While multiple challenges remain before clinical readiness, a SLAM algorithm-based endoscopic endonasal surgery navigation system has the potential to improve surgical efficiency, economy of motion, and safety.

Elevated risk of recurrence and retreatment for silent pituitary adenomas.

PURPOSE: Pituitary adenomas are the most common tumor of the pituitary gland and comprise nearly 15% of all intracranial masses. These tumors are stratified into functional or silent categories based on their pattern of hormone expression and secretion. Preliminary evidence supports differential clinical outcomes between some functional pituitary adenoma (FPA) subtypes and silent pituitary adenoma (SPA) subtypes. METHODS: We collected and analyzed the medical records of all patients undergoing resection of SPAs or FPAs from a single high-volume neurosurgeon between 2007 and 2018 at Brigham and Women's Hospital. Descriptive statistics and the Mantel-Cox log-rank test were used to identify differences in outcomes between these cohorts, and multivariate logistic regression was used to identify predictors of radiographic recurrence for SPAs. RESULTS: Our cohort included 88 SPAs and 200 FPAs. The majority of patients in both cohorts were female (48.9% of SPAs and 63.5% of FPAs). SPAs were larger in median diameter than FPAs (2.1 cm vs. 1.2 cm, p < 0.001). The most frequent subtypes of SPA were gonadotrophs (55.7%) and corticotrophs (30.7%). Gross total resection (GTR) was achieved in 70.1% of SPA resections and 86.0% of FPA resections (p < 0.001). SPAs had a higher likelihood of recurring (hazard ratio [HR] 3.2, 95% confidence interval [95%CI] 1.6-7.2) and a higher likelihood of requiring retreatment for recurrence (HR 2.5; 95%CI 1.0-6.1). Subset analyses revealed that recurrence and retreatment were more both likely for subtotally resected SPAs than subtotally resected FPAs, but this pattern was not observed in SPAs and FPAs after GTR. Among SPAs, recurrence was associated with STR (odds ratio [OR] 9.3; 95%CI 1.4-64.0) and younger age (OR 0.92 per year; 95%CI 0.88-0.98) in multivariable analysis. Of SPAs that recurred, 12 of 19 (63.2%) were retreated with repeat surgery (n = 11) or radiosurgery (n = 1), while the remainder were observed (n = 7).There were similar rates of recurrence across different SPA subtypes. CONCLUSION: Patients undergoing resection of SPAs should be closely monitored for disease recurrence through more frequent clinical follow-up and diagnostic imaging than other adenomas, particularly among patients with STR and younger patients. Several patients can be observed after radiographic recurrence, and the decision to retreat should be individualized. Longitudinal clinical follow-up of SPAs, including an assessment of symptoms, endocrine function, and imaging remains critical.

Influences of compound age and identity in the effectiveness of insect quinone secretions against the fungus Beauveria bassiana.

Chemical defences against parasites and pathogens can be seen in a wide range of animal taxa, including insect pests such as the red flour beetle Tribolium castaneum. Antimicrobial quinone-based secretions can be used by these beetles to defend against various parasites, particularly the fungal entomopathogen Beauveria bassiana. While quinone secretions can inhibit B. bassiana growth, it is unknown how long they remain effective or how individual secretion compounds contribute to growth inhibition. Here, we tested each individual component of the quinone secretions (methyl-1,4-benzoquinone, ethyl-1,4-benzoquinone, and 1-pentadecene), as well as two mixed solutions that represent the composition range found in natural T. castaneum secretions, after aging for 0, 24, or 72 h. The two quinone compounds equally contributed to B. bassiana inhibition, but their efficacy was significantly reduced after 24 h, with no growth inhibition after 72 h. This indicates that quinones protect insects against B. bassiana for only a limited time, perhaps requiring constant secretion into the environment to effectively defend against this fungal threat. Future investigations may consider the extent to which quinone secretions are effective against other parasites, as well as how their ability to cause parasite damage changes with compound age.