NECAB family of neuronal calcium-binding proteins in health and disease.

The N-terminal EF-hand calcium-binding proteins 1-3 (NECAB1-3) constitute a family of predominantly neuronal proteins characterized by the presence of at least one EF-hand calcium-binding domain and a functionally less well characterized C-terminal antibiotic biosynthesis monooxygenase domain. All three family members were initially discovered due to their interactions with other proteins. NECAB1 associates with synaptotagmin-1, a critical neuronal protein involved in membrane trafficking and synaptic vesicle exocytosis. NECAB2 interacts with predominantly striatal G-protein-coupled receptors, while NECAB3 partners with amyloid-ß A4 precursor protein-binding family A members 2 and 3, key regulators of amyloid-ß production. This demonstrates the capacity of the family for interactions with various classes of proteins. NECAB proteins exhibit distinct subcellular localizations: NECAB1 is found in the nucleus and cytosol, NECAB2 resides in endosomes and the plasma membrane, and NECAB3 is present in the endoplasmic reticulum and Golgi apparatus. The antibiotic biosynthesis monooxygenase domain, an evolutionarily ancient component, is akin to atypical heme oxygenases in prokaryotes but is not well-characterized in vertebrates. Prokaryotic antibiotic biosynthesis monooxygenase domains typically form dimers, suggesting that calcium-mediated conformational changes in NECAB proteins may induce antibiotic biosynthesis monooxygenase domain dimerization, potentially activating some enzymatic properties. However, the substrate for this enzymatic activity remains uncertain. Alternatively, calcium-mediated conformational changes might influence protein interactions or the subcellular localization of NECAB proteins by controlling the availability of protein-protein interaction domains situated between the EF hands and the antibiotic biosynthesis monooxygenase domain. This review summarizes what is known about genomic organization, tissue expression, intracellular localization, interaction partners, and the physiological and pathophysiological role of the NECAB family.

Phlebotomy-induced anemia reduces oxygen-induced retinopathy severity and dampens retinal developmental transcriptomic pathways in rats.

BACKGROUND: Phlebotomy-induced-anemia (PIA), which induces tissue hypoxia and angiogenesis, occurs universally among infants at risk for severe retinopathy of prematurity (ROP). We hypothesized that PIA exacerbates pathologic retinal neovascularization in ROP. METHODS: We induced PIA to a hematocrit of 18% among rats undergoing the established 50/10 oxygen-induced retinopathy (OIR) model. Rats were euthanized at P15 and P20, during the avascular and neovascular phases of OIR, respectively. Retinal vascular morphometry, cytokine/chemokine concentrations, transcriptomes, and mRNA expression of angiogenic and iron-deficiency markers were compared to non-PIA controls. RESULTS: In OIR, PIA decreased percent avascular area at P15 by 35%, percent neovascular area at P20 by 42%, and select pro-inflammatory cytokine/chemokine concentrations at both time points. At P20, PIA increased mRNA expression of angiopoietin 2/ vascular endothelial growth factor-A 2-fold and transferrin and transferrin receptor 5-fold. RNA sequencing showed dampened pathways of angiogenesis, inflammation, and neural development in anemic OIR females. CONCLUSION: Contrary to our hypothesis, PIA decreased OIR severity and retinal cytokine and chemokine levels and dampened transcriptomic pathways central to retinal vascular and neural development in neonatal rats. These data suggest PIA provides a protective effect from OIR. Further investigation into the functional effect of these molecular changes is warranted. IMPACT: This is the first preclinical study to investigate the impact of neonatal anemia on oxygen-induced retinopathy (OIR) outcomes. This study adds to the literature that anemia decreases neovascularization, decreases cytokine and chemokine levels, and dampens angiogenic and neural transcriptomic pathways in the rat 50/10 OIR model. The study identifies a sex-specific transcriptomic response to anemia in the 50/10 OIR model, with females primarily impacted.

The RNA receptor RIG-I binding synthetic oligodeoxynucleotide promotes pneumonia survival.

Pneumonia is a worldwide threat to public health, demanding novel preventative and therapeutic strategies. The lung epithelium is a critical environmental interface that functions as a physical barrier to pathogen invasion while also actively sensing and responding to pathogens. We have reported that stimulating lung epithelial cells with a combination therapeutic consisting of a diacylated lipopeptide and a synthetic CpG oligodeoxynucleotide (ODN) induces synergistic pneumonia protection against a wide range of pathogens. We report here that mice deficient in Toll-like receptor 9 (TLR9), the previously described receptor for ODN, still displayed partial ODN-induced protection. This prompted us to seek an alternate ODN receptor, and we discovered by mass spectroscopy that the RNA sensor RIG-I could also bind DNA-like ODN. ODN binding by RIG-I resulted in MAVS-dependent pneumonia-protective signaling events. While RIG-I is essential to native defenses against viral infections, we report that therapeutic RIG-I activation with ODN promoted pathogen killing and host survival following both viral and bacterial challenges. These data indicate that maximal ODN-induced pneumonia protection requires activation of both TLR9/MyD88 and RIG-I/MAVS signaling pathways. These findings not only identify what we believe to be a novel pattern recognition receptor for DNA-like molecules, but reveal a potential therapeutic strategy to protect susceptible individuals against lethal pneumonias during periods of peak vulnerability.

Biologically-informed Killer cell immunoglobulin-like receptor (KIR) gene annotation tool.

Natural killer (NK) cells are essential components of the innate immune system, with their activity significantly regulated by Killer cell Immunoglobulin-like Receptors (KIRs). The diversity and structural complexity of KIR genes present significant challenges for accurate genotyping, essential for understanding NK cell functions and their implications in health and disease. Traditional genotyping methods struggle with the variable nature of KIR genes, leading to inaccuracies that can impede immunogenetic research. These challenges extend to high-quality phased assemblies, which have been recently popularized by the Human Pangenome Consortium. This paper introduces BAKIR (Biologically-informed Annotator for KIR locus), a tailored computational tool designed to overcome the challenges of KIR genotyping and annotation on high-quality, phased genome assemblies. BAKIR aims to enhance the accuracy of KIR gene annotations by structuring its annotation pipeline around identifying key functional mutations, thereby improving the identification and subsequent relevance of gene and allele calls. It uses a multi-stage mapping, alignment, and variant calling process to ensure high-precision gene and allele identification, while also maintaining high recall for sequences that are significantly mutated or truncated relative to the known allele database. BAKIR has been evaluated on a subset of the HPRC assemblies, where BAKIR was able to improve many of the associated annotations and call novel variants. BAKIR is freely available on GitHub, offering ease of access and use through multiple installation methods, including pip, conda, and singularity container, and is equipped with a user-friendly command-line interface, thereby promoting its adoption in the scientific community.

Pulmonary vascular structure and function are related to exercise capacity in health and COPD.

BACKGROUND: Although it is generally accepted that aerobic exercise training does not change lung structure or function, some work suggests that greater pulmonary vascular structure and function is associated with higher exercise capacity (VO2peak). RESEARCH QUESTION: Is there a cross-sectional association between the pulmonary vasculature and VO2peak? We hypothesized that those with higher computed tomography (CT) blood vessel volumes, and pulmonary diffusing capacity for carbon monoxide (DLCO) would have higher VO2peak, independent of airflow limitation. STUDY DESIGN AND METHODS: Participants from the CanCOLD study were categorized as: never-smokers with normal spirometry (n=263); ever-smokers with normal spirometry (n=407); and chronic obstructive pulmonary disease (COPD): individuals with spirometric airflow obstruction (n=334). Total vessel volume (TVV), the volume for all vessels with a cross-sectional area ≤5 mm2 (BV5), and between 5-10 mm2 (BV5-10) were generated from CT scans and used as indices of pulmonary vascular structure. DLCO was used as an index of pulmonary microvascular function. VO2peak was evaluated via incremental cardiopulmonary exercise testing. RESULTS: General linear regression models revealed that even after controlling for FEV1, emphysema severity and body morphology, DLCO, TVV, BV5 and BV5-10, were independently associated with VO2peak. Interaction effects were observed between COPD and TVV, BV5, and BV5-10 indicating a weaker association between pulmonary vascular volumes and VO2peak in COPD. INTERPRETATION: Our results suggest that pulmonary vascular structure and DLCO is independently associated with VO2peak, regardless of severity of airflow limitation and emphysema, suggesting that these associations are not limited to COPD.

Metabolic engineering of yeast for de novo production of kratom monoterpene indole alkaloids.

Monoterpene indole alkaloids (MIAs) from Mitragyna speciosa ("kratom"), such as mitragynine and speciogynine, are promising novel scaffolds for opioid receptor ligands for treatment of pain, addiction, and depression. While kratom leaves have been used for centuries in South-East Asia as stimulant and pain management substance, the biosynthetic pathway of these psychoactives have only recently been partially elucidated. Here, we demonstrate the de novo production of mitragynine and speciogynine in Saccharomyces cerevisiae through the reconstruction of a five-step synthetic pathway from common MIA precursor strictosidine comprising fungal tryptamine 4-monooxygenase to bypass an unknown kratom hydroxylase. Upon optimizing cultivation conditions, a titer of ∼290 µg/L kratom MIAs from glucose was achieved. Untargeted metabolomics analysis of lead production strains led to the identification of numerous shunt products derived from the activity of strictosidine synthase (STR) and dihydrocorynantheine synthase (DCS), highlighting them as candidates for enzyme engineering to further improve kratom MIAs production in yeast. Finally, by feeding fluorinated tryptamine and expressing a human tailoring enzyme, we further demonstrate production of fluorinated and hydroxylated mitragynine derivatives with potential applications in drug discovery campaigns. Altogether, this study introduces a yeast cell factory platform for the biomanufacturing of complex natural and new-to-nature kratom MIAs derivatives with therapeutic potential.

Genomic signature for oligometastatic disease in non-small cell lung cancer patients with brain metastases.

Purpose/objectives: Biomarkers for extracranial oligometastatic disease remain elusive and few studies have attempted to correlate genomic data to the presence of true oligometastatic disease. Methods: Patients with non-small cell lung cancer (NSCLC) and brain metastases were identified in our departmental database. Electronic medical records were used to identify patients for whom liquid biopsy-based comprehensive genomic profiling (Guardant Health) was available. Extracranial oligometastatic disease was defined as patients having ≤5 non-brain metastases without diffuse involvement of a single organ. Widespread disease was any spread beyond oligometastatic. Fisher's exact tests were used to screen for mutations statistically associated (p<0.1) with either oligometastatic or widespread extracranial disease. A risk score for the likelihood of oligometastatic disease was generated and correlated to the likelihood of having oligometastatic disease vs widespread disease. For oligometastatic patients, a competing risk analysis was done to assess for cumulative incidence of oligometastatic progression. Cox regression was used to determine association between oligometastatic risk score and oligoprogression. Results: 130 patients met study criteria and were included in the analysis. 51 patients (39%) had extracranial oligometastatic disease. Genetic mutations included in the Guardant panel that were associated (p<0.1) with the presence of oligometastatic disease included ATM, JAK2, MAP2K2, and NTRK1, while ARID1A and CCNE1 were associated with widespread disease. Patients with a positive, neutral and negative risk score for oligometastatic disease had a 78%, 41% and 11.5% likelihood of having oligometastatic disease, respectively (p<0.0001). Overall survival for patients with positive, neutral and negative risk scores for oligometastatic disease was 86% vs 82% vs 64% at 6 months (p=0.2). Oligometastatic risk score was significantly associated with the likelihood of oligoprogression based on the Wald chi-square test. Patients with positive, neutral and negative risk scores for oligometastatic disease had a cumulative incidence of oligometastatic progression of 77% vs 35% vs 33% at 6 months (p=0.03). Conclusions: Elucidation of a genomic signature for extracranial oligometastatic disease derived from non-invasive liquid biopsy appears feasible for NSCLC patients. Patients with this signature exhibited higher rates of early oligoprogression. External validation could lead to a biomarker that has the potential to direct local therapies in oligometastatic patients.

Neurodiversity in the Minds of Students: From Perception to Campus Programming.

Neurodiversity is a social justice movement at the nexus of neuroscience, academia, and public policy. A contemporary view of neurodiversity is one that embraces neurological differences, encompassing all "neurotypes," including more specific identifiers like autistic or dyslexic. The goal of this study was to investigate student awareness and perception of neurodiversity since they are the next generation of public policy makers. Students enrolled in Introduction to Behavioral Neuroscience (N=146) were exposed to different information sources (popular, academic, TED talk, or choose/find their own) on the topic of neurodiversity. They then wrote a paper where they summarized: a) the information source used, b) their ideas to better support a neurodiverse society, and c) their opinions on aspects of neurodiversity. Several important findings emerged. First, 64% of the sample had never heard of the term neurodiversity; this class was their first exposure to it. Second, students conducting their own searches on neurodiversity had the highest level of optimism (p < 0.05) that society was ready to accept neurodiversity. Students identified even higher rates of receptivity (85%) amongst their friends. Third, student ideas to advance neurodiversity were organized into more salient categories for campuses to consider. Our findings challenge neuroscience programs to consider their role in providing "first exposure" opportunities to students in the diversity, equity, and inclusion realm, especially in areas directly related to our field. We also discuss the growing relevance of neurodiversity in research and academia and offer programming possibilities to enhance neurodiversity awareness and support on college campuses.

Metagenomic, metabolomic, and lipidomic shifts associated with fecal microbiota transplantation for recurrent Clostridioides difficile infection.

Recurrent C. difficile infection (rCDI) is an urgent public health threat, for which the last resort and lifesaving treatment is a fecal microbiota transplant (FMT). However, the exact mechanisms that mediate a successful FMT are not well-understood. Here, we use longitudinal stool samples collected from patients undergoing FMT to evaluate intra-individual changes in the microbiome, metabolome, and lipidome after successful FMTs relative to their baselines pre-FMT. We show changes in the abundance of many lipids, specifically a decrease in acylcarnitines post-FMT, and a shift from conjugated bile acids pre-FMT to deconjugated secondary bile acids post-FMT. These changes correlate with a decrease in Enterobacteriaceae, which encode carnitine metabolism genes, and an increase in Lachnospiraceae, which encode bile acid altering genes such as bile salt hydrolases (BSHs) and the bile acid-inducible (bai) operon, post-FMT. We also show changes in gut microbe-encoded amino acid biosynthesis genes, of which Enterobacteriaceae was the primary contributor to amino acids C. difficile is auxotrophic for. Liquid chromatography, ion mobility spectrometry, and mass spectrometry (LC-IMS-MS) revealed a shift from microbial conjugation of primary bile acids pre-FMT to secondary bile acids post-FMT. Here, we define the structural and functional changes associated with a successful FMT and generate hypotheses that require further experimental validation. This information is meant to help guide the development of new microbiota-focused therapeutics to treat rCDI.IMPORTANCERecurrent C. difficile infection is an urgent public health threat, for which the last resort and lifesaving treatment is a fecal microbiota transplant. However, the exact mechanisms that mediate a successful FMT are not well-understood. Here, we show changes in the abundance of many lipids, specifically acylcarnitines and bile acids, in response to FMT. These changes correlate with Enterobacteriaceae pre-FMT, which encodes carnitine metabolism genes, and Lachnospiraceae post-FMT, which encodes bile salt hydrolases and baiA genes. There was also a shift from microbial conjugation of primary bile acids pre-FMT to secondary bile acids post-FMT. Here, we define the structural and functional changes associated with a successful FMT, which we hope will help aid in the development of new microbiota-focused therapeutics to treat rCDI.

Quality Assessment of Tomato Paste Products on the Ghanaian Market: An Insight Into Their Possible Adulteration.

Tomato paste is the most consumed tomato product on the Ghanaian market, the majority of which are imported into the country. This food product is easily adulterated, and thus, routine quality checks are necessary. Therefore, the current study is aimed at assessing the quality of eight tomato paste products on the Ghanaian market and checking for the presence of starch and artificial colourant erythrosine as possible adulterants. Routine quality metrics such as the pH, titratable acidity, total solids, and total soluble solids were assessed using standard methods. An HPLC method was employed to detect the presence of the colourant erythrosine, whereas starch content was determined by an enzymatic method using α-amylase and then amyloglucosidase. Fifty percent of the products did not qualify to be called tomato paste based on total solid estimation. All the sampled products contained some amount of starch, with three having more than 10 g/100 g of this thickener. Additionally, the banned colourant erythrosine was detected in two of the products. All other parameters were consistent with regulatory standards. The present study has shown that some tomato paste products on the Ghanaian market contain additives that are not permitted under any circumstance and fall short of regulatory standards.

Foreign body suture granuloma in canthal surgery: association with suture type.

PURPOSE: Foreign body suture reaction ("suture granuloma") is a complication faced by all surgeons. The purpose of this study was to examine the incidence and risk factors of suture granulomas in canthal surgery. METHODS: An IRB-approved retrospective review of medical records identified patients who had canthal surgery. Statistical analysis was performed on multiple data points to determine associations with granuloma formation. Summary statistics were reported as a mean and standard deviation for continuous variables, and as frequencies or proportions for categorical variables. Effect estimates were reported as odds ratios. A p-value of less than .05 was deemed statistically significant. RESULTS: A total of 758 procedures were included. Seven commonly used suture materials were encountered including uncoated polyester, polyester coated with polytetramethylene adipate (PTMA), nylon, polydioxanone, polyester coated with polytetrafluoroethylene (PTFE), polypropylene, and polyglactin 910. Eighteen total granulomas were observed (2.4%). Fifteen granulomas were associated with uncoated polyester, two with polyester coated with PTFE, and one with polypropylene. The odds of developing a suture granuloma with uncoated polyester were 25.4 times as likely as polyglactin 910 (p = .04). The odds of developing a suture granuloma with a non-absorbable, braided suture were 23.2 times as likely as absorbable, braided suture (p = .04). There was no significant association identified between the other collected variables. CONCLUSIONS: Foreign body suture granulomas occur at a low rate following canthal surgery and can be largely avoided through careful selection of resorbable or monofilament sutures.

Consensus Statement of the National Association of EMS Physicians International Association of Fire Chiefs and the International Association of Chiefs of Police: Best Practices for Collaboration Between Law Enforcement and Emergency Medical Services During Acute Behavioral Emergencies.

Emergency Medical Services (EMS) and law enforcement (LE) frequently work as a team in encounters with individuals experiencing acute behavioral emergencies manifesting with severe agitation and aggression. The optimal management is a rehearsed, coordinated effort by law enforcement and EMS providing the necessary interventions to address behaviors that endanger the patient, the responders, and the public. The purpose of this document is to provide guidance and direction in the shared responsibility of managing and caring for a person displaying behavioral instability with irrational, agitated, and/or violent behavior. This is a discussion of the roles of law enforcement, 9-1-1 call centers (hereafter referred to as the Emergency Call Centers or "ECCs"), Fire, and EMS. A coordinated and unified response enhances the safety and effective management of potentially serious situations posed by individuals experiencing such acute behavioral emergencies. This paper provides the framework for an approach endorsed by NAEMSP, IACP, and the IAFC.

Primary Malignant Meningeal Melanoma Complicated by Cerebral Venous Sinus Thrombosis: An Illustrative Case With a Systematic Review of the Literature.

Melanocytic tumors of the central nervous system (CNS) such as meningeal melanoma are exceedingly rare tumours derived from leptomeningeal melanocytes. We report an illustrative case of a previously healthy 47-year-old male who presented with tonic-clonic seizure. Magnetic resonance imaging (MRI) with contrast demonstrated a homogenously enhancing right temporal extra-axial lesion. The patient was stabilized on anti-epileptic medications and dexamethasone prior to proceeding with complete surgical resection of the lesion. Intraoperatively, the lesion was heavily pigmented with invasion of the surrounding dura and skull. Histopathology revealed a poorly differentiated neoplasm with nuclear atypia and melanin-containing cells with strong SOX10 and variable S100 positivity. Computed tomography (CT) of the chest, abdomen, and pelvis showed no metastatic disease, and molecular profiling was negative including absent BRAF mutation. He began checkpoint inhibitor therapy and subsequently developed cerebral venous sinus thrombosis managed with anticoagulation. Sixteen months post-operatively, he was neurologically intact, working full-time, and had resumed immunotherapy. We systematically reviewed the literature on primary intracranial malignant melanoma (PIMM) with the goal of understanding the prognosis and best treatment options for this disease. Our systematic review produced 82 articles (118 unique cases) of PIMM. The average age at diagnosis was 45.9 years (95% CI:42.9-48.9), and headache (54.2%) was the most common initial presentation. Eighty-nine percent of patients had primary surgical resection, and 41.0% of these individuals experienced a recurrence with a mean time to recurrence of 19.6 months (95% CI:6.95-32.23). Adjuvant therapy was administered in 65.7% of surgically resected patients; including radiotherapy, chemotherapy, immunotherapy, or a combination. In summary, PIMM is a rare tumour that can appear radiographically similar to meningioma. The results of our systematic review demonstrate that surgical resection remains the mainstay of therapy for best long-term prognosis.

Situations predisposing primary care patients to use antibiotics without a prescription in the United States.

Background: Patients' situations can impact their intentions to use antibiotics without medical guidance (non-prescription use) in the future. This survey determines the prevalence of intended (future) use of non-prescription antibiotics for 13 predefined situations and identifies the sociodemographic characteristics associated with intended use for these types of situations. Methods: Patient surveys (N = 564) were conducted from January 2020 to June 2021 in the waiting rooms of 6 safety-net primary care clinics and 2 emergency departments in a private healthcare system. We used principal component analysis to identify 3 situational summary factors: barriers to a doctor visit, accessibility of non-prescription antibiotics, and previous symptom relief with antibiotics. Multivariate linear regression identified the sociodemographic predictors associated with each summary factor. Results: The most common situations triggering patients to use non-prescription antibiotics were a perceived high cost of doctor visits (29.8%), having leftover prescription antibiotics (50.4%), and experiencing symptom relief with prior use of antibiotics (47.5%). Multivariate regression results revealed that younger patients (P < 0.04) and patients attending the safety-net health system (P < 0.001) had more intended use of non-prescription antibiotics for all 3 summary factors. Conclusions: Future stewardship interventions should consider the types of situations that drive patients' decisions to use antibiotics without a prescription. Interventions aimed at reducing barriers to health care (eg, high costs and long waits associated with doctor appointments) and educating individuals on medically appropriate, nonantibiotic treatment options may reduce antibiotic use and antimicrobial resistance.

Injury epidemiology in male and female competitive diving athletes: A four-year observational study.

OBJECTIVES: To describe the incidence, severity, burden and sport specific characteristics of injuries reported in elite diving athletes. DESIGN: Descriptive epidemiology study. METHODS: Medical attention and time-loss injuries from 63 (43 female, 20 male) Australian national diving programme athletes were prospectively collected over four seasons (September 2018-August 2022). Injury incidence rates and burden were calculated, standardised per 365 athlete days, and compared across groups using negative binomial generalised linear models. RESULTS: In total 421 injuries were reported (female = 292, male = 129) at an injury incidence rate of 2.36 (95 % confidence interval = 2.14-2.60) per 365 athlete days. Annual injury prevalence ranged from 70.0 to 85.1 %. Approximately two-thirds of injuries (67.2 %) resulted in a period of time-loss. The overall injury burden was 91 days of absence (95 % confidence interval = 81-102) per 365 athlete days. Stress fractures in springboard diving athletes incurred the largest mean days of time-loss compared to other injured tissue types. The majority of injuries were reported to occur during training (79.3 %) as opposed to competition (2.4 %), with more than half (55.3 %) of all reported injuries occurring during pool training sessions. Water entry (30.4 %) or take-off (27.8 %) were the most frequently reported mechanism of injury. CONCLUSIONS: Annual injury prevalence reported in competitive Australian diving athletes was found to be high. Contrary to existing literature, competitive diving injuries were reported to occur within the daily training environment, with few injuries occurring during competition. Notable injury differences between springboard and platform athletes were observed.

Return to work and self-reported swallowing following transoral robotic surgery for early-stage oropharyngeal squamous cell carcinoma: A retrospective cohort study.

BACKGROUND: Treatment de-intensification, including transoral robotic surgery (TORS), may outcomes in HPV-positive oropharyngeal squamous cell carcinoma (OPSCC). Early return to work (RTW) improves quality of life in oncology patients. Our objective was to compare the RTW time in OPSCC patients undergoing primary TORS or chemoradiotherapy (CRT). We investigated the role of treatment modality on self-reported swallowing function. METHODS: All patients were adults diagnosed with early-stage (T1-2, N0-2) OPSCC and treated via primary TORS or CRT. We performed 1:1 exact case matching based on tumor stage and subsite. We collected RTW outcomes for all patients. We also reported MD Anderson Dysphagia Index (MDADI) scores up to 24 months from the end of treatment. We performed statistical analyses and comparison of RTW and MDADI outcomes based on treatment group. RESULTS: Overall, 26 patients undergoing primary TORS and 25 undergoing primary CRT were included. We found a significant improvement in RTW in TORS patients compared to CRT (TORS: 54 days (1.8 months), IQR: 30.8; CRT: 164 days (5.4 months), IQR: 109; W=587, p = 9.28e-08) independent of HPV status, tonsillar subsite, and radiotherapy alone. Primary TORS had a 16.2-fold (95 % CI: 5.78-45.5) higher likelihood of returning to work than primary CRT patients. Primary TORS also had better MDADI scores within two years of treatment. CONCLUSIONS: In OPSCC, primary TORS accelerated RTW and improved swallowing when compared to primary CRT. The potential economic advantage of returning to work sooner should be discussed when reviewing treatment options with patients.

Five days of inpatient scoliosis-specific exercises improve preoperative spinal flexibility and facilitate curve correction of patients with rigid idiopathic scoliosis.

Preoperative spine flexibility plays a key role in the intraoperative treatment course of severe scoliosis. In this cohort study, we examined the effects of 5 day inpatient scoliosis-specific exercise (SSE) on the spinal flexibility of patients with adolescent idiopathic scoliosis before surgery. A total of 65 patients were analyzed. These patients were divided into a prospective cohort (n = 43, age: 15 ± 1.6 years, 36 girls and 7 boys, Lenke class 1 and 2, Cobb angle: 64 ± 11°) who underwent spinal fusion in 2020, and a retrospective cohort (n = 22, age: 15 ± 1.5 years, 17 girls and 5 boys, Lenke class 1 or 2, Cobb angle: 63 ± 10°), who underwent surgery between 2018 and 2019 and did not receive preoperative SSE. Rigid scoliosis was defined as a reduction of less than 50% in Cobb angle between the preoperative fulcrum bending and initial standing curve magnitude. In the prospective cohort, 21 patients (Cobb angle: 65 ± 11°) presented with rigid thoracic scoliosis (pre-SSE fulcrum bending: 40 ± 9°, 39% reduction), and therefore received 5-day SSE to improve their preoperative spinal flexibility (SSE group), whereas 22 patients (Cobb angle: 63 ± 12°) presented with flexible thoracic scoliosis (pre-SSE fulcrum bending: 27 ± 8°, 58% reduction), and therefore underwent surgery without preoperative SSE (non-SSE group). For patients who received 5-day preoperative SSE for 4 h every day, the International Schroth Three-Dimensional Scoliosis Therapy technique was implemented with an inpatient model. After 5 days of SSE, improvements in Cobb angle with post-SSE fulcrum-bending radiography (23 ± 7°, 66% reduction) and pulmonary function (forced expiratory volume in 1 s/forced expiratory volume: 87% before SSE and 92% after SSE, p < 0.01) were observed. At the postoperative day 5, the degree of scoliosis had reduced from 44 ± 6.6° to 22 ± 6° in the SSE group, which is 1° less than the Cobb angle obtained on post-SSE fulcrum-bending radiography. In the non-SSE group, the degree of scoliosis decreased to 26 ± 5.7°. In the retrospective cohort, the degree of scoliosis decreased to 35 ± 5°, with the group also having higher postoperative pain (Visual Analog Scale score = 7, range = 5-10) and an extended hospitalization duration (11 ± 3 days). At 2-year follow-up, curve correction was found to be maintained without adding-on or proximal junctional kyphosis. Compared with the non-SSE group, the SSE group exhibited a greater curve correction (66%) with a shorter hospitalization duration (5 ± 1 days) and a lower degree of postoperative pain (Visual Analog Scale score = 4, range = 3-8). Taken together, our findings indicate that 5 day SSE improves preoperative spinal flexibility and facilitates curve correction.