Oxytocin signaling is necessary for synaptic maturation of adult-born neurons.

Neural circuit plasticity and sensory response dynamics depend on forming new synaptic connections. Despite recent advances toward understanding the consequences of circuit plasticity, the mechanisms driving circuit plasticity are unknown. Adult-born neurons within the olfactory bulb have proven to be a powerful model for studying circuit plasticity, providing a broad and accessible avenue into neuron development, migration, and circuit integration. We and others have shown that efficient adult-born neuron circuit integration hinges on presynaptic activity in the form of diverse signaling peptides. Here, we demonstrate a novel oxytocin-dependent mechanism of adult-born neuron synaptic maturation and circuit integration. We reveal spatial and temporal enrichment of oxytocin receptor expression within adult-born neurons in the murine olfactory bulb, with oxytocin receptor expression peaking during activity-dependent integration. Using viral labeling, confocal microscopy, and cell type-specific RNA-seq, we demonstrate that oxytocin receptor signaling promotes synaptic maturation of newly integrating adult-born neurons by regulating their morphological development and expression of mature synaptic AMPARs and other structural proteins.

The ACE inhibitor captopril inhibits ACN-1 to control dauer formation and aging.

The renin-angiotensin-aldosterone system (RAAS) plays a well-characterized role regulating blood pressure in mammals. Pharmacological and genetic manipulation of the RAAS has been shown to extend lifespan in Caenorhabditis elegans, Drosophila and rodents, but its mechanism is not well defined. Here, we investigate the angiotensin-converting enzyme (ACE) inhibitor drug captopril, which extends lifespan in worms and mice. To investigate the mechanism, we performed a forward genetic screen for captopril-hypersensitive mutants. We identified a missense mutation that causes a partial loss of function of the daf-2 receptor tyrosine kinase gene, a powerful regulator of aging. The homologous mutation in the human insulin receptor causes Donohue syndrome, establishing these mutant worms as an invertebrate model of this disease. Captopril functions in C. elegans by inhibiting ACN-1, the worm homolog of ACE. Reducing the activity of acn-1 via captopril or RNA interference promoted dauer larvae formation, suggesting that acn-1 is a daf gene. Captopril-mediated lifespan extension was abrogated by daf-16(lf) and daf-12(lf) mutations. Our results indicate that captopril and acn-1 influence lifespan by modulating dauer formation pathways. We speculate that this represents a conserved mechanism of lifespan control.

Orbital Richter Transformation With Subsequent Orbital MALT-type Lymphoma in a Patient With Chronic Lymphocytic Leukemia.

A 74-year-old man with a history of chronic lymphocytic leukemia (CLL) presented with large salmon-colored patch lesions along the inferior fornix and superotemporal conjunctiva of the OS. The patient underwent an incisional biopsy of the lesions, which showed a CLL with areas of large B-cell lymphoma, consistent with Richter transformation. Following medical and radiation-based therapy of these lesions, the patient returned 3 months later with inferomedial preseptal swelling in the contralateral eye, which biopsy proved to be recurrent/resistant low-grade CLL with a posttreatment extranodal marginal zone B-cell lymphoma pattern. This case exemplifies a rare presentation of CLL with Richter transformation and a recurrent/resistant posttreatment orbital CLL with a marginal zone B-cell lymphoma-like pattern.

Age and number of lesions predict chalazion recurrence.

PURPOSE: Periocular lesions in pediatric patients usually require general anesthesia for surgical intervention. The US Food and Drug Administration (FDA) warns against multiple exposures to anesthesia in children younger than 3 years due to the increased risk of learning disabilities in this population. This study aimed to evaluate risk factors associated with chalazion recurrence after surgery. METHODS: A retrospective chart review over a five-year period identified 649 patients at our institution undergoing surgical intervention for chalazion. The primary outcomes examined were as follows: (1) return to the operating room for additional surgical intervention and (2) recurrence of chalazion during convalescence from surgery and follow-up. RESULTS: Fewer than one-third of patients suffered a recurrence after surgery. Multivariate logistic regression found younger age (p = 0.01), female sex (p = 0.01), and a greater number of chalazia drained (p < 0.001) were significantly correlated with recurrence of chalazia after surgery. CONCLUSIONS: Patients presenting at a younger age and with a greater number of chalazion were statistically more likely to have a recurrence of chalazion after surgery. Given recurrence is more likely in younger children, reconciling this with the risk-benefit ratio with regard to FDA guidelines on anesthesia in children under three years is a critical consideration for ophthalmologists.

Predictors of postoperative performance status after surgical management of infratemporal fossa malignancies.

Infratemporal fossa (ITF) tumors are difficult to access surgically due to anatomical constraints. Moreover, aggressive ITF carcinomas and sarcomas necessitate aggressive treatment strategies that, along with tumor-related symptoms, contribute to decreases in patient performance status. To assess factors that predict postoperative performance in patients undergoing surgery for ITF tumors. We reviewed medical records for all patients surgically treated for an ITF malignancy between January 1, 1999, and December 31, 2017, at our institution. We collected patient demographics, preoperative performance, tumor stage, tumor characteristics, treatment modalities, pathological data, and postoperative performance data. The 5-year survival rate was 62.2%. Higher preoperative Karnofsky Performance Status (KPS) score (n = 64; p < 0.001), short length of stay (p = 0.002), prior surgery at site (n = 61; p = 0.0164), and diagnosis of sarcoma (n = 62; p = 0.0398) were predictors of higher postoperative KPS scores. Percutaneous endoscopic gastrostomy (PEG) (n = 9; p = 0.0327), and tracheostomy tube placement (n = 20; p = 0.0436) were predictors of lower postoperative KPS scores, whereas age at presentation (p = 0.72), intracranial tumor spread (p = 0.8197), and perineural invasion (n = 40; p = 0.2195) were not. Male patients and patients with carcinomas showed the greatest decreases in KPS scores between pretreatment and posttreatment. Higher preoperative KPS score and short length of stay were the best predictors of higher postoperative KPS scores. This work provides treatment teams and patients with better information on outcomes for shared decision-making.

A CRISPR toolbox for generating intersectional genetic mouse models for functional, molecular, and anatomical circuit mapping.

BACKGROUND: The functional understanding of genetic interaction networks and cellular mechanisms governing health and disease requires the dissection, and multifaceted study, of discrete cell subtypes in developing and adult animal models. Recombinase-driven expression of transgenic effector alleles represents a significant and powerful approach to delineate cell populations for functional, molecular, and anatomical studies. In addition to single recombinase systems, the expression of two recombinases in distinct, but partially overlapping, populations allows for more defined target expression. Although the application of this method is becoming increasingly popular, its experimental implementation has been broadly restricted to manipulations of a limited set of common alleles that are often commercially produced at great expense, with costs and technical challenges associated with production of intersectional mouse lines hindering customized approaches to many researchers. Here, we present a simplified CRISPR toolkit for rapid, inexpensive, and facile intersectional allele production. RESULTS: Briefly, we produced 7 intersectional mouse lines using a dual recombinase system, one mouse line with a single recombinase system, and three embryonic stem (ES) cell lines that are designed to study the way functional, molecular, and anatomical features relate to each other in building circuits that underlie physiology and behavior. As a proof-of-principle, we applied three of these lines to different neuronal populations for anatomical mapping and functional in vivo investigation of respiratory control. We also generated a mouse line with a single recombinase-responsive allele that controls the expression of the calcium sensor Twitch-2B. This mouse line was applied globally to study the effects of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) on calcium release in the ovarian follicle. CONCLUSIONS: The lines presented here are representative examples of outcomes possible with the successful application of our genetic toolkit for the facile development of diverse, modifiable animal models. This toolkit will allow labs to create single or dual recombinase effector lines easily for any cell population or subpopulation of interest when paired with the appropriate Cre and FLP recombinase mouse lines or viral vectors. We have made our tools and derivative intersectional mouse and ES cell lines openly available for non-commercial use through publicly curated repositories for plasmid DNA, ES cells, and transgenic mouse lines.

Preferential use of total intravenous anesthesia in ambulatory otolaryngology surgery during the COVID-19 pandemic.

The novel coronavirus (SARS-CoV-2 or COVID-19) pandemic has impacted nearly every aspect of otolaryngologic practice. The transition from office-based evaluation to telemedicine and the number of postponed elective surgical cases is unprecedented. There is a significant need to resume elective surgical care for these patients at the appropriate time. As practices begin to move towards resuming elective and same day ambulatory surgery, safety of both the patient and healthcare team is of paramount importance. Usage of total intravenous anesthesia (propofol and remifentanil) over volatile gas anesthesia (e.g., sevoflurane) may increase the number of patients able to safely receive care by reducing potential spread of the virus through reduction in coughing and significantly decreasing the time spent in the recovery room.

A Primary Care Ultrasound Fellowship: Training for Clinical Practice and Future Educators.

As ultrasound devices become smaller, more portable, and more user friendly, there is now widespread use of this technology by physicians of all specialties, yet there are currently few structured opportunities for ultrasound education outside of emergency and critical care medicine. Anticipating the rising educational demand in the primary care specialties, the University of South Carolina School of Medicine created a primary care ultrasound fellowship in 2011, the first yearlong training program in point-of-care ultrasonography for graduates of internal medicine, medicine-pediatrics, pediatrics, and family medicine residencies. This paper reviews the history of point-of-care ultrasonography fellowships and then provides an overview of the primary care ultrasound fellowship.

An Inexpensive and Easy Ultrasound Phantom: A Novel Use for SPAM.

Ultrasound models, commonly referred to as "phantoms," are simulation tools for ultrasound education. Commercially produced phantoms are available, but there are "homemade" alternatives such as raw poultry and gelatin molds. Precooked, processed meat, better known as SPAM (Hormel Foods Corporation, Austin, MN), can be used as an ultrasound phantom to teach several ultrasound applications. It is a versatile, hygienic, and easily manipulated medium that does not require refrigeration or preparatory work and can be easily discarded at the end of use.

Phosphorus recovery from pig manure solids prior to land application.

Land disposal of pig manure is an environmental concern due to an imbalance of the nitrogen to phosphorus (N:P) ratio for crop production, leading to excess phosphorus (P) in soils and potential risks of water pollution. A process called "quick wash" was investigated for its feasibility to extract and recover P from pig manure solids. This process consists of selective dissolution of P from solid manure into a liquid extract using mineral or organic acid solutions, and recovery of P from the liquid extract by adding lime and an organic polymer to form a P precipitate. Laboratory tests confirmed the quick wash process selectively removed and recovered up to 90% of the total (TP) from fresh pig manure solids while leaving significant amounts of nitrogen (N) in the washed manure residue. As a result of manure P extraction, the washed solid residue became environmentally safer for land application with a more balanced N:P ratio for crop production. The recovered P can be recycled and used as fertilizer for crop production while minimizing manure P losses into the environment.

Evolution of a genetic incompatibility in the genus Xiphophorus.

Genetic incompatibilities are commonly observed between hybridizing species. Although this type of isolating mechanism has received considerable attention, we have few examples describing how genetic incompatibilities evolve. We investigated the evolution of two loci involved in a classic example of a Bateson-Dobzhansky-Muller (BDM) incompatibility in Xiphophorus, a genus of freshwater fishes from northern Central America. Hybrids develop a lethal melanoma due to the interaction of two loci, an oncogene and its repressor. We cloned and sequenced the putative repressor locus in 25 Xiphophorus species and an outgroup species, and determined the status of the oncogene in those species from the literature. Using phylogenetic analyses, we find evidence that a repeat region in the proximal promoter of the repressor is coevolving with the oncogene. The data support a hypothesis that departs from the standard BDM model: it appears the alleles that cause the incompatibilities have coevolved simultaneously within lineages, rather than in allopatric or temporal isolation.

Optimal sensor locations for the backward lagrangian stochastic technique in measuring lagoon gas emission.

This study evaluated the impact of gas concentration and wind sensor locations on the accuracy of measuring gas emission rates from a lagoon environment using the backward Lagrangian stochastic (bLS) inverse-dispersion technique. Path-integrated concentrations (PICs) and three-dimensional (3D) wind vector data were collected at different locations within the lagoon landscape. A floating 45 m × 45 m perforated pipe network on an irrigation pond was used as a synthetic distributed emission source for the controlled release of methane. A total of 961 15-min datasets were collected under different atmospheric stability conditions over a 2-yr period. The PIC location had a significant impact on the accuracy of the bLS technique. The location of the 3D sonic anemometer was generally not a factor for the measured accuracies with the PIC positioned on the downwind berm. The PICs across the middle of the pond consistently produced the lowest accuracy with any of the 3D anemometer locations (<69% accuracy). The PICs located on the downwind berm consistently yielded the best bLS accuracy regardless of whether the 3D sonic anemometer was located on the upwind, side, or downwind berm (accuracies ranged from 79 to 108%). The accuracies of the emission measurements with the berm PIC-berm 3D setting were statistically similar to that found in a more ideal homogeneous grass field. Considering the practical difficulties of setting up equipment and the accuracies associated with various sensor locations, we recommend that wind and concentration sensors be located on the downwind berm.

Rabies postexposure prophylaxis protocol option for unvaccinated domestic animals, Texas: 2010-2019.

OBJECTIVE: To assess data on rabies postexposure prophylaxis (PEP) in domestic animals following Texas' protocol and to describe preexposure and postexposure vaccination failures from 2010 through 2019. ANIMALS: 1,218 unvaccinated animals that received PEP, 925 unvaccinated animals that were euthanatized instead of receiving PEP, and 3 preexposure vaccinated dogs that developed rabies. METHODS: Zoonotic incident reports from 2010 through 2019 were reviewed for information regarding animals with no known rabies vaccination that received PEP or were euthanatized in accordance with state protocol after exposure to a laboratory-confirmed rabid animal; reports were also reviewed for any preexposure and postexposure vaccination failures. The state-required PEP protocol was to immediately vaccinate the animal against rabies, confine the animal for 90 days, and administer booster vaccines during the third and eighth weeks of the confinement period. RESULTS: From 2010 through 2019, 1,218 exposed animals received PEP; 99.8% did not develop rabies. Three failures were recorded, all in animals < 12 weeks of age when PEP was initiated. Additionally, 925 exposed animals were euthanatized instead of receiving PEP. One true preexposure vaccination failure was recorded. CLINICAL RELEVANCE: The Texas PEP protocol was used during the 10-year period. Results indicated that this protocol is a viable option for unvaccinated domestic animals exposed to rabies. Alternative protocols warrant additional consideration.

Monoclonal antibodies in neuro-ophthalmology.

Neuro-ophthalmologic diseases include a broad range of disorders affecting the afferent and efferent visual pathways. Recently, monoclonal antibody (mAb) therapies have emerged as a promising targeted approach in the management of several of these complex conditions. Here, we describe the mechanism-specific applications and advancements in neuro-ophthalmologic mAb therapies. The application of mAbs in neuro-ophthalmologic diseases highlights our increasing understanding of disease-specific mechanisms in autoimmune conditions such as neuromyelitis optica, thyroid eye disease, and myasthenia gravis. Due to the specificity of mAb therapies, applications in neuro-ophthalmologic diseases have yielded exceptional clinical outcomes, including both reduced rate of relapse and progression to disability, visual function preservation, and quality of life improvement. These advancements have not only expanded the range of treatable neuro-ophthalmologic diseases but also reduced adverse events and increased the response rate to treatment. Further research into neuro-ophthalmologic disease mechanisms will provide accurate and specific targeting of important disease mediators through applications of future mAbs. As our understanding of these diseases and the relevant therapeutic targets evolve, we will continue to build on our understanding of how mAbs interfere with disease pathogenesis, and how these changes improve clinical outcomes and quality of life for patients.

Safety of Ambulatory Surgery For Obstructive Sleep Apnea: A Retrospective Review.

OBJECTIVE: Assess the safety of ambulatory surgery performed for obstructive sleep apnea. STUDY DESIGN: Retrospective chart review. SETTING: Tertiary care hospital. METHODS: Demographic data including age, gender, race, body mass index, insurance status, socioeconomic status, and distance traveled for surgery was collected, as well as comorbidities, and apnea-hypopnea index (AHI). Outcome variables included continuous positive airway pressure reinitiation, planned/unplanned postoperative admission, emergency department (ED) presentation, or readmission within 7 and 14 days of surgery. RESULTS: A total of 601 patients were included, who underwent sleep surgery between 2017 and 2022. The median age was 55 years [interquartile range: 19]. A total of 437 patients (73%) were male, 502 (84%) were Caucasian, and the median distance traveled was 20 miles [27]. The median AHI was 27.1 [26]. A total of 286 hypoglossal nerve stimulators, 12 tonsillectomies, 160 expansion sphincteroplasties (ESP), and 201 nasal procedures were performed. There were 9 (1%) planned and 23 (4%) total admissions postoperatively. Sixteen patients (2%) presented to ED within 7 days, and 22 (3%) within 14 days. Nine (1%) were readmitted within 7 days, and 12 (2%) within 14 days. There were significantly more planned admissions, unplanned admissions, ED presentations, and readmissions for ESP. There were no significant differences in demographic or clinical data between patients who underwent single versus multiple surgeries. CONCLUSION: Outpatient sleep surgery is generally safe. Close postoperative monitoring is necessary and overnight observation should be considered in those with very severe sleep apnea and/or significant comorbidities. The distance a patient travels should also be considered for overnight admission.

Neural landscape is associated with functional outcomes in irradiated patients with oropharyngeal squamous cell carcinoma.

The incidence of human papilloma virus-mediated oropharyngeal squamous cell carcinoma (OPSCC) has increased over the past 40 years, particularly among young individuals with a favorable prognosis; however, current therapy often leads to unfortunate side effects, such as dysphagia. Despite the emphasis on dysphagia in previous studies, there is an important research gap in understanding the correlation between neuronal changes and patient-reported and functional outcomes in patients with OPSCC. To address this issue, we examined pathologic tissue samples from patients with OPSCC using multiplex immunofluorescence staining and machine learning to correlate tumor-associated neuronal changes with prospectively collected patient-reported and functional outcomes. We found that tumor enrichment of adrenergic (TH+) and CGRP+ sensory-afferent nerves correlated with poorer swallowing outcomes. Functional electromyography recordings showed correlations between growing (GAP43+) and immature cholinergic (ChAT+DCX+) nerves and denervation patterns in survivors of OPSCC. A murine model of radiation-induced dysphagia further confirmed that immature cholinergic and CGRP+ nerves were correlated with impaired swallowing. Preclinical interventional studies also supported the independent contributions of CGRP+ and cholinergic (ChAT+) nerves to dysphagia in treated mouse models of OPSCC. Our results suggest that CGRP+ and ChAT+ neuronal signaling play distinct roles in tumor- and radiation-induced dysphagia in OPSCC and offer a comprehensive dataset on the neural landscape of OPSCC. These insights may guide early interventions for swallow preservation and the repurposing of neurology-related drugs, such as CGRP blockers, in clinical oncology and survivorship.

Microbial community analysis of swine wastewater anaerobic lagoons by next-generation DNA sequencing.

Anaerobic lagoons are a standard practice for the treatment of swine wastewater. This practice relies heavily on microbiological processes to reduce concentrated organic material and nutrients. Despite this reliance on microbiological processes, research has only recently begun to identify and enumerate the myriad and complex interactions that occur in this microbial ecosystem. To further this line of study, we utilized a next-generation sequencing (NGS) technology to gain a deeper insight into the microbial communities along the water column of four anaerobic swine wastewater lagoons. Analysis of roughly one million 16S rDNA sequences revealed a predominance of operational taxonomic units (OTUs) classified as belonging to the phyla Firmicutes (54.1%) and Proteobacteria (15.8%). At the family level, 33 bacterial families were found in all 12 lagoon sites and accounted for between 30% and 50% of each lagoon's OTUs. Analysis by nonmetric multidimensional scaling (NMS) revealed that TKN, COD, ORP, TSS, and DO were the major environmental variables in affecting microbial community structure. Overall, 839 individual genera were classified, with 223 found in all four lagoons. An additional 321 genera were identified in sole lagoons. The top 25 genera accounted for approximately 20% of the OTUs identified in the study, and the low abundances of most of the genera suggests that most OTUs are present at low levels. Overall, these results demonstrate that anaerobic lagoons have distinct microbial communities which are strongly controlled by the environmental conditions present in each individual lagoon.

Total Intravenous Anesthesia Versus Inhaled Sevoflurane in Obstructive Sleep Apnea Surgery: A Randomized Controlled Trial.

OBJECTIVE: Specific guidelines regarding an optimal general anesthesia (GA) approach to obstructive sleep apnea (OSA) patients remain undefined. Literature comparing the efficacy of total intravenous anesthesia (TIVA) and inhalational anesthesia in this population is sparse. We hypothesize that OSA patients receiving TIVA will experience reduced recovery times and other improved post-surgical outcomes. STUDY DESIGN: Randomized controlled trial. METHODS: Adult OSA patients undergoing upper airway surgery (hypoglossal nerve stimulation [HNS], nasal, or palate surgery) from February 2020-December 2020 were included. A post-anesthesia care unit (PACU) nursing survey documented patients' alertness, pain, oxygen supplementation, and postoperative nausea and vomiting from PACU arrival to 2 hours. Perioperative timepoints from the electronic medical record (EMR) and a nurse-estimated Phase I recovery time were collected. RESULTS: One hundred eleven patients were included (46 TIVA and 65 inhalational anesthesia). Per EMR-recorded timepoints, TIVA patients undergoing HNS and palate surgery experienced Phase I Time reductions of 12.5 min (p = 0.042) and 27.5 min (p = 0.016), respectively. Per the PACU survey, TIVA patients undergoing any surgery, HNS, or palate surgery experienced nurse-estimated Phase I Time reductions of 16.5 min (p = 0.004), 12.5 min (p = 0.031), and 38.5 min (p = 0.024), respectively. Overall, TIVA patients experienced higher alertness and pain ratings, and lower oxygen supplementation requirements from PACU arrival to 30 min (p < 0.05). CONCLUSION: Patients with OSA receiving TIVA for GA maintenance during upper airway procedures experienced reduced recovery times and oxygen supplementation requirements, and a more rapid return to alertness. Future work toward developing optimized anesthetic guidelines for OSA patients is merited. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:984-992, 2023.

Lymphocytic Panhypophysitis Mimicking Glaucoma: Case Report.

Lymphocytic hypophysitis (LH) is a primary inflammatory disorder of the pituitary gland and infundibulum that commonly manifests in both mass effect and endocrinologic symptoms. Although the exact pathophysiology remains unclear, it has been increasingly linked to an autoimmune process. Complications arise by two separate mechanisms. Inflammation in the sella can lead to headaches and visual field defects. Pituitary inflammation and, chronically, fibrosis interfere with the gland's hormone-secreting capacity, often resulting in various endocrinopathies such as polyuria, polydipsia, amenorrhea, and others. While final histologic classification requires pathologic evaluation, diagnosis can often be made clinically with appropriate imaging. Treatment often consists of conservative management but can also include glucocorticoids or surgical resection. We present a case of biopsy-proven LH involving the entire pituitary, dubbed lymphocytic panhypophysitis (LPH) that was misdiagnosed for years as glaucoma due to the lack of endocrinopathy as well as delay in magnetic resonance imaging. After imaging revealed the sellar mass, the patient responded symptomatically to surgical resection and glucocorticoid treatment. LPH may present without endocrinologic symptoms and therefore mimic alternate diagnoses such as glaucoma. Clinicians should be suspicious of a diagnosis of glaucoma in the setting of a temporal field defect and lack of response to traditional therapy. A personal or family history of autoimmune disease in such patients should prompt further imaging and investigation. Therefore, endocrinopathy is supportive but not present in every case of LPH.