Preoperative Acetaminophen For Microsuspension Laryngoscopy Reduces Postoperative Opioid Use.

OBJECTIVES: The opioid crisis has prompted consideration of analgesic prescriptions. This study explored the value of preoperative acetaminophen for pain control following microsuspension laryngoscopy (MSL) and compared the results with a previous study of pain and opioid use following MSL (Tsang et al.). METHODS: A prospective open-label clinical trial was conducted in patients undergoing MSL. All patients were administered preoperative acetaminophen. Short-form McGill Pain Questionnaire (SF-MPQ), pain visual analogue scale (VAS), and present pain intensity (PPI) scores were collected preoperatively and on postoperative days (PODs) 1, 3, 7, and 14. Statistical analysis identified variables associated with opioid use or increased pain scores, and compared outcomes with Tsang et al. RESULTS: Eighty-nine patients were included (mean age 52.8 ± 17.3 years, 40 males). All patients received preoperative 1 g acetaminophen (77 (86.5%) orally) with no adverse effects. On POD1, opioid usage was 10%. Median [IQR] pain scores were 5 [2-11], 21 [12.3-56.8], and 3 [2-3.3] on SF-MPQ, VAS, and PPI, respectively. Post-Anesthesia Care Unit (PACU) opioid requirements significantly correlated with POD1 opioid consumption (τb = 0.214; p ≤ 0.05), and significant associations with PACU opioid administration were found for total anesthesia time (OR (95%CI) = 1.271 (1.043-1.548), p = 0.017) and total laryngoscope suspension time (OR (95%CI) = 0.791 (0.651-0.962, p = 0.019)). This cohort demonstrated reduced opioid usage on POD1 compared with Tsang et al (23%). CONCLUSIONS: Preoperative acetaminophen is a safe intervention, resulting in decreased postoperative opioid use following MSL. Anesthesia time correlated with need for postoperative opioids. LEVEL OF EVIDENCE: Level 4 Laryngoscope, 2024.

Scapular morphology does not predict supraspinatus tendon tear propagation following an individualised exercise therapy programme.

Purpose: To determine whether scapular morphology could predict isolated supraspinatus tendon tear propagation after exercise therapy. We hypothesised that a larger critical shoulder angle (CSA) and type III acromial morphology predict a positive change in tear size. Methods: Fifty-nine individuals aged 40-70 years with isolated symptomatic high-grade partial or full-thickness supraspinatus tendon tears were included. Individuals participated in a structured, individualised 12-week exercise therapy programme and underwent ultrasound to measure tear size at baseline and 12 months following therapy. Computed tomography images were segmented to create three-dimensional subject-specific bone models and reviewed by three trained clinicians to measure CSA and to determine acromion morphology based on the Bigliani classification. A binary logistic regression was performed to determine the predictive value of CSA and acromion morphology on tear propagation. Results: The CSA was 30.0 ± 5.4°. Thirty-one individuals (52.5%) had type II acromial morphology, followed by type III and type I morphologies (25.4% and 22.0%, respectively); 81.4% experienced no change in tear size, four (6.8%) individuals experienced tear propagation and seven (11.9%) individuals had a negative change in tear size. No significant difference in tear propagation rates based on CSA or acromion morphology (not significant [NS]) was observed. The model predicted tear size status in 81.4% of cases but only predicted tear propagation 8.3% of the time. Overall, CSA and acromion morphology only predicted 24.3% (R 2 = 0.243) of variance in tear propagation (NS). Conclusions: CSA and acromion morphology were NS predictors of tear propagation of the supraspinatus tendon 12 months following an individualised exercise therapy programme. Level of Evidence: II.

Modelling the innate immune system in microphysiological systems.

This critical review aims to highlight how modeling of the immune response has adapted over time to utilize microphysiological systems. Topics covered here will discuss the integral components of the immune system in various human body systems, and how these interactions are modeled using these systems. Through the use of microphysiological systems, we have not only expanded on foundations of basic immune cell information, but have also gleaned insight on how immune cells work both independently and collaboratively within an entire human body system.

Clinical characteristics and surgical outcomes of epilepsy associated with temporal encephalocele: A systematic review.

Temporal encephaloceles (TE) are an under-identified, potentially intervenable cause of epilepsy. This systematic review consolidates the current data to identify the major clinical, neuroimaging, and EEG features and surgical outcomes of epilepsy associated with TE. Literature searches were carried out using MEDLINE, Embase, PsycINFO, Scopus, and Cochrane Library databases from inception to December 7, 2023. Studies were included if they described clinical, neuroimaging, EEG, or surgical data in ≥5 patients with TE and epilepsy. Of 562 studies identified in the search, 24 met the eligibility criteria, reporting 423 unique patients with both epilepsy and TE. Compared to epilepsy patients without TE, those with TE had a higher mean age of seizure onset and were less likely to have a history of febrile seizures. Seizure semiologies were variable, but primarily mirrored temporal lobe onset patterns. Epilepsy patients with TE had a higher likelihood of having clinical or radiographic features of idiopathic intracranial hypertension (IIH) than those without. Brain MRI may show ipsilateral mesial temporal sclerosis (16 %). CT scans of the skull base usually revealed bony defects near the TE (90 %). Brain PET scans primarily showed ipsilateral temporal lobe hypometabolism (80 %), mostly in the anterior temporal lobe (67 %). Scalp EEG mostly lateralized ipsilateral to the implicated TE (92 % seizure onset) and localized to the temporal lobe (96 %). Intracranial EEG revealed seizure onset near the TE (11 of 12 cases including TE-adjacent electrodes) with variable timing of spread to the ipsilateral hippocampus. After surgical treatment of the TE, the rate of Engel I or ILAE 1 outcomes at one year was 75 % for lesionectomy, 85 % for anterior temporal lobectomy (ATL), and 80 % for ATL with amygdalohippocampectomy. Further studies are needed to better elucidate the relationship between IIH, TE, and epilepsy, improve the identification of TE, and optimize surgical interventions.

Cyprocide selectively kills nematodes via cytochrome P450 bioactivation.

Left unchecked, plant-parasitic nematodes have the potential to devastate crops globally. Highly effective but non-selective nematicides are justifiably being phased-out, leaving farmers with limited options for managing nematode infestation. Here, we report our discovery of a 1,3,4-oxadiazole thioether scaffold called Cyprocide that selectively kills nematodes including diverse species of plant-parasitic nematodes. Cyprocide is bioactivated into a lethal reactive electrophilic metabolite by specific nematode cytochrome P450 enzymes. Cyprocide fails to kill organisms beyond nematodes, suggesting that the targeted lethality of this pro-nematicide derives from P450 substrate selectivity. Our findings demonstrate that Cyprocide is a selective nematicidal scaffold with broad-spectrum activity that holds the potential to help safeguard our global food supply.

Cryptic Cerulenin Rearrangement in Ketosynthase Covalent Inhibition.

The antibiotic cerulenin is a fungal natural product identified as a covalent inhibitor of ketosynthases within fatty acid and polyketide biosynthesis. Due to its selective and potent inhibitory activity, cerulenin has found significant utility in multidisciplinary biochemical, biomedical, and clinical studies. Although its covalent inhibition profile has been confirmed, cerulenin's mechanism has not been fully determined at a molecular level, frustrating the drug development of related analogues. Herein, we describe the use of stable isotopic tracking with NMR and MS methods to unravel the covalent mechanism of cerulenin against type II fatty acid ketosynthases. We detail the discovery of a unique C2-C3 retro-aldol bond cleavage and a structural rearrangement upon covalent inhibition of cerulenin at the active cysteine residue in E. coli type II fatty acid ketosynthases FabB and FabF.

Accounting for imperfect detection when estimating species-area relationships and beta-diversity.

Ecologists have historically quantified fundamental biodiversity patterns, including species-area relationships (SARs) and beta diversity, using observed species counts. However, imperfect detection may often bias derived community metrics and subsequent community models. Although several statistical methods claim to correct for imperfect detection, their performance in species-area and ß-diversity research remains unproven. We examine inaccuracies in the estimation of SARs and ß-diversity parameters that emerge from imperfect detection, and whether such errors can be mitigated using a non-parametric diversity estimator (iNEXT.3D) and Multi-Species Occupancy Models (MSOMs). We simulated 28,350 sampling regimes of 2835 fragmented communities, varying the mean and standard deviation of species detection probabilities, and the number of sampling repetitions. We then quantified the bias, accuracy, and precision of derived estimates of model coefficients for SARs and the effects of patch area on ß-diversity (pairwise Sørensen similarity). Imperfect detection biased estimates of all evaluated parameters, particularly when mean detection probabilities were low, and there were few sampling repetitions. Observed counts consistently underestimated species richness and SAR z-values, and overestimated SAR c-values; iNEXT.3D and MSOMs only partially resolved these biases. iNEXT.3D provided the best estimates of SAR z-values, although MSOM estimates were generally comparable. All three methods accurately estimated pairwise Sørensen similarity in most circumstances, but only MSOMs provided unbiased estimates of the coefficients of models examining covariate effects on ß-diversity. Even when using iNEXT.3D or MSOMs, imperfect detection consistently caused biases in SAR coefficient estimates, calling into question the robustness of previous SAR studies. Furthermore, the inability of observed counts and iNEXT.3D to estimate ß-diversity model coefficients resulted from a systematic, area-related bias in Sørensen similarity estimates. Importantly, MSOMs corrected for these biases in ß-diversity assessments, even in suboptimal scenarios. Nonetheless, as estimator performance consistently improved with increasing sampling repetitions, the importance of appropriate sampling effort cannot be understated.

Immunohistochemical Expression of Ki-67 and p53 and Their Prognostic Role in Ameloblastoma: A Longitudinal Study.

Objectives: Ameloblastoma, comprising approximately 11% of all odontogenic tumors, is a locally aggressive tumor with a high recurrence rate. This study aimed to assess the immunohistochemical expression of Ki-67 and p53 and their association with clinical and pathological factors among patients with ameloblastoma. Methods: Retrospective follow-up data of patients histologically confirmed with ameloblastoma at Makerere College of Health Sciences in Kampala, Uganda from January 2012 to December 2018 were retrieved. Factors associated with Ki-67 and p53 immunohistochemical expression were determined using one-way one-way analysis of variance. Chi-square and Fisher's exact statistical tests were used to assess factors associated with recurrence. A two-tailed p < 0.05 was considered statistically significant. Results: A total of 40 patients confirmed histologically with ameloblastoma were included in the analysis. The majority (62.5%) of cases were of the conventional type of ameloblastoma. The expressions of Ki-67 and p53 were 52.5% and 85.0%, respectively. Recurrence was found in 47.5% of patients and it was associated with conventional histological type (p=0.042), segmental resection (p < 0.001), tumor size (p < 0.001), and high p53 expression (p=0.041). Conclusions: Almost half the cases in this study had recurrence. The immunohistochemical expression of p53 was significantly higher than that of Ki-67.

Revision Total Hip Arthroplasty: Evaluating the Utility of the Geriatric Nutritional Risk Index as a Risk Stratification Tool.

Background: This study investigates the association between the Geriatric Nutritional Risk Index (GNRI), a measure of malnutrition risk, and 30-day postoperative complications following revision total hip arthroplasty (rTHA). Methods: The American College of Surgeons National Surgical Quality Improvement Program database was queried for all patients ≥65 who underwent aseptic rTHA between 2015 and 2021. The final study population (n = 7119) was divided into 3 groups based on preoperative GNRI: normal/reference (GNRI >98) (n = 4342), moderate malnutrition (92 ≤ GNRI ≤98) (n = 1367), and severe malnutrition (GNRI <92) (n = 1410). Multivariate logistic regression analysis was conducted to investigate the association between preoperative GNRI and 30-day postoperative complications. Results: After controlling for significant covariates, the risk of experiencing any postoperative complications was significantly higher with both moderate (odds ratio [OR] 2.08, P < .001) and severe malnutrition (OR 8.79, P < .001). Specifically, moderate malnutrition was independently and significantly associated with deep vein thrombosis (OR 1.01, P = .044), blood transfusions (OR 1.78, P < .001), nonhome discharge (OR 1.83, P < .001), readmission (OR 1.27, P = .035), length of stay >2 days (OR 1.98, P < .001), and periprosthetic fracture (OR 1.54, P = .020). Severe malnutrition was independently and significantly associated with sepsis (OR 3.67, P < .001), septic shock (OR 3.75, P = .002), pneumonia (OR 2.73, P < .001), urinary tract infection (OR 2.04, P = .002), deep vein thrombosis (OR 1.01, P = .001), pulmonary embolism (OR 2.47, P = .019), acute renal failure (OR 8.44, P = .011), blood transfusions (OR 2.78, P < .001), surgical site infection (OR 2.59, P < .001), nonhome discharge (OR 3.36, P < .001), readmission (OR 1.69, P < .001), unplanned reoperation (OR 1.97, P < .001), length of stay >2 days (OR 5.41, P < .001), periprosthetic fractures (OR 1.61, P = .015), and mortality (OR 2.63, P < .001). Conclusions: Malnutrition has strong predictive value for short-term postoperative complications and has potential as an adjunctive risk stratification tool for geriatric patients undergoing rTHA.

Impact of Frailty on Surgical Outcomes of Patients With Cushing Disease Using the Multicenter Registry of Adenomas of the Pituitary and Related Disorders Registry.

BACKGROUND AND OBJECTIVES: Despite growing interest in how patient frailty affects outcomes (eg, in neuro-oncology), its role after transsphenoidal surgery for Cushing disease (CD) remains unclear. We evaluated the effect of frailty on CD outcomes using the Registry of Adenomas of the Pituitary and Related Disorders (RAPID) data set from a collaboration of US academic pituitary centers. METHODS: Data on consecutive surgically treated patients with CD (2011-2023) were compiled using the 11-factor modified frailty index. Patients were classified as fit (score, 0-1), managing well (score, 2-3), and mildly frail (score, 4-5). Univariable and multivariable analyses were conducted to examine outcomes. RESULTS: Data were analyzed for 318 patients (193 fit, 113 managing well, 12 mildly frail). Compared with fit and managing well patients, mildly frail patients were older (mean ± SD 39.7 ± 14.2 and 48.9 ± 12.2 vs 49.4 ± 8.9 years, P < .001) but did not different by sex, race, and other factors. They had significantly longer hospitalizations (3.7 ± 2.0 and 4.5 ± 3.5 vs 5.3 ± 3.5 days, P = .02), even after multivariable analysis (ß = 1.01, P = .007) adjusted for known predictors of prolonged hospitalization (age, Knosp grade, surgeon experience, American Society of Anesthesiologists grade, complications, frailty). Patients with mild frailty were more commonly discharged to skilled nursing facilities (0.5% [1/192] and 4.5% [5/112] vs 25% [3/12], P < .001). Most patients underwent gross total resection (84.4% [163/193] and 79.6% [90/113] vs 83% [10/12]). No difference in overall complications was observed; however, venous thromboembolism was more common in mildly frail (8%, 1/12) than in fit (0.5%, 1/193) and managing well (2.7%, 3/113) patients (P = .04). No difference was found in 90-day readmission rates. CONCLUSION: These results demonstrate that mild frailty predicts CD surgical outcomes and may inform preoperative risk stratification. Frailty-influenced outcomes other than age and tumor characteristics may be useful for prognostication. Future studies can help identify strategies to reduce disease burden for frail patients with hypercortisolemia.

Amphiphilic Heparinoids as Potent Antiviral Agents against SARS-CoV-2.

Herein, we report the synthesis and biological evaluation of a novel series of heparinoid amphiphiles as inhibitors of heparanase and SARS-CoV-2. By employing a tailor-made synthetic strategy, a library of highly sulfated homo-oligosaccharides bearing d-glucose or a C5-epimer (i.e., l-idose or l-iduronic acid) conjugated with various lipophilic groups was synthesized and investigated for antiviral activity. Sulfated higher oligosaccharides of d-glucose or l-idose with lipophilic aglycones displayed potent anti-SARS-CoV-2 and antiheparanse activity, similar to or better than pixatimod (PG545), and were more potent than their isosteric l-iduronic acid congeners. Lipophilic groups such as cholestanol and C18-aliphatic substitution are more advantageous than functional group appended lipophilic moieties. These findings confirm that fine-tuning of higher oligosaccharides, degree of sulfation, and lipophilic groups can yield compounds with potent anti-SARS-CoV-2 activity.

Complications and putative risk factors for cecal or colonic surgery in dogs: 79 cases (2002-2015).

OBJECTIVES: To evaluate the complication rate, mortality rate and putative risk factors for cecal or colonic surgery in dogs. MATERIALS AND METHODS: A multi-institutional retrospective study including dogs that had undergone surgery that involved the cecum or the colon. Medical records from three referral hospitals were reviewed for patient demographics and clinical data. The association between putative risk factors and survival to discharge or complications was assessed using univariable and multivariable analysis. RESULTS: Seventy-nine dogs met the criteria to be included in this study. Fifty-five dogs had full thickness incision surgeries, while 24 dogs had partial thickness surgeries. The complication and mortality rates for full thickness and partial thickness cecal/colonic surgeries were not statistically different. The dehiscence rate of colonic anastomosis in this study was four of 47 (8.5%). On univariate analysis, performing full thickness procedures out of hours had an association with increased complications and mortality. On multivariable analysis, no factors were associated with survival to discharge or complications. There was no association of board-certified surgeon presence in surgery with complications or mortality. CLINICAL SIGNIFICANCE: The performance of full thickness cecal/colonic surgery is not associated with a statistically significant increased risk for complications or mortality compared to partial thickness procedures, with a possible increased risk of complications and mortality in full thickness procedures out of hours.

Movement of juvenile migratory birds from settlement to adulthood across the non-breeding range.

Among migratory vertebrates, high levels of fidelity to non-breeding sites during adulthood are common. If occupied sites vary in quality, strong site fidelity can have profound consequences for individual fitness and population demography. Given the prevalence of adult site fidelity, the regions of the non-breeding range to which juveniles first migrate, and the scale of any subsequent movements, are likely to be pivotal in shaping distributions and demographic processes across population ranges. However, inherent difficulties in tracking migratory individuals through early life mean that opportunities to quantify juvenile settlement and movements across non-breeding ranges, and the mechanisms involved, are extremely rare. Through long-term, range-wide resightings of hundreds of colour-marked individuals from their first migration to adulthood and the application of state-space models, we quantify levels of juvenile and adult regional-scale movements and distances at different life stages across the whole non-breeding distribution range in a migratory shorebird, the Black-tailed Godwit (Limosa limosa islandica). We show that the probability of individuals changing non-breeding regions (seven historical wintering regions spanning the Western Europe range) at all ages is very low (mean movement probability = 10.9% from first to subsequent winter, and 8.3% from first adult winter to later winters). Movement between regions was also low between autumn and winter of the same year for both juveniles (mean movement probability = 17.0%) and adults (10.4%). The great majority of non-breeding movements from the first autumn to adulthood were within regions and less than 100 km. The scarcity of regional-scale non-breeding movements from the first autumn to adulthood means that the factors influencing where juveniles settle will be key determinants of non-breeding distributions and of the rate and direction of changes in distributions.

Should I stay or should I go? An exploratory study comparing wheelchair-adapted rowing at home vs. in community gyms.

PURPOSE: Wheelchair users experience many barriers to physical activity as affordable and accessible exercise equipment options are limited. Thus, the home-based adapted rower (aROW) and gym-based aROW were developed. The objectives were to determine: 1) wheelchair users' preferences, perspectives, facilitators, and barriers to using the home-based versus the gym-based aROW, 2) perceived usability of the home and gym aROWs, and 3) recommendations to adapt the aROW further for home and community use. MATERIALS AND METHODS: In this two-phase exploratory mixed-methods study, participants completed one month of using a home aROW, followed by one month of using a community gym aROW. After each phase, participants completed a semi-structured interview and the System Usability Scale (SUS) questionnaire. Interview data were analyzed using conventional content analysis and effect size comparing SUS data was calculated. RESULTS AND CONCLUSIONS: Four categories were identified: what worked well, barriers to using the aROWs, what could be improved and important considerations. There was a large effect size in perceived usability between the aROWs with participants preferring the home aROW. Overall, rowing was enjoyable, and participants achieved positive physical outcomes. As preferences are individual, the home aROW provides wheelchair users with a potential choice between home or gym exercise.

Rowing is an enjoyable and effective form of aerobic exercise for wheelchair usersWheelchair users experience social, environment and financial barriers to engaging in exerciseThe home aROW provides a low-cost and accessible option for wheelchair-adapted aerobic exercise.

The Quest for an Integrated Set of Neural Mechanisms Underlying Object Recognition in Primates.

Inferences made about objects via vision, such as rapid and accurate categorization, are core to primate cognition despite the algorithmic challenge posed by varying viewpoints and scenes. Until recently, the brain mechanisms that support these capabilities were deeply mysterious. However, over the past decade, this scientific mystery has been illuminated by the discovery and development of brain-inspired, image-computable, artificial neural network (ANN) systems that rival primates in these behavioral feats. Apart from fundamentally changing the landscape of artificial intelligence, modified versions of these ANN systems are the current leading scientific hypotheses of an integrated set of mechanisms in the primate ventral visual stream that support core object recognition. What separates brain-mapped versions of these systems from prior conceptual models is that they are sensory computable, mechanistic, anatomically referenced, and testable (SMART). In this article, we review and provide perspective on the brain mechanisms addressed by the current leading SMART models. We review their empirical brain and behavioral alignment successes and failures, discuss the next frontiers for an even more accurate mechanistic understanding, and outline the likely applications.

Outcomes following minimally invasive dorsal cheilectomy for hallux rigidus: A systematic review.

BACKGROUND: Cheilectomy of the 1st metatarsophalangeal joint (MTPJ) is one of the most common procedures for the management of hallux rigidus. However, there is no consensus regarding outcomes following minimally invasive dorsal cheilectomy (MIDC) for the management of hallux rigidus. AIM: To evaluate outcomes following MIDC for the management of hallux rigidus. METHODS: During November 2023, the PubMed, EMBASE and Cochrane Library databases were systematically reviewed to identify clinical studies examining outcomes following MIDC for the management of hallux rigidus. RESULTS: Six studies were included. In total, 348 patients (370 feet) underwent MIDC for hallux rigidus at a weighted mean follow-up of 37.9 ± 16.5 months. The distribution of patients by Coughlin and Shurna's classification was recorded in 4 studies as follows: I (58 patients, 27.1%), II (112 patients, 52.3%), III (44 patients, 20.6%). Three studies performed an additional 1st MTPJ arthroscopy and debridement following MIDC. Retained intra-articular bone debris was observed in 100% of patients in 1 study. The weighted mean American orthopedic foot and ankle society score improved from a preoperative score of 68.9 ± 3.2 to a postoperative score of 87.1. The complication rate was 8.4%, the most common of which was persistent joint pain and stiffness. Thirty-two failures (8.7%) were observed. Thirty-three secondary procedures (8.9%) were performed at a weighted mean time of 8.6 ± 3.2 months following the index procedure. CONCLUSION: This systematic review demonstrated improvements in subjective clinical outcomes together with a moderate complication rate following MIDC for the management of hallux rigidus at short-term follow-up. A moderate re-operation rate at short-term follow-up was recorded. The marked heterogeneity between included studies and paucity of high quality comparative studies limits the generation of any robust conclusions.