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This clinical report describes the design and fabrication of an implant-retained and soft-tissue-supported obturator prosthesis and a magnetic retained midfacial prosthesis for a patient with a midfacial defect following bilateral total maxillectomy, removal of the left zygoma, and excision of the entire upper lip. The patient underwent multiple head and neck surgeries for 4 separate primary oral cancers, 1 recurrence, and 1 pulmonary metastasis. The definitive obturator prosthesis was retained by 1 zygomatic implant with soft-tissue support and retention. The midfacial prosthesis was attached to the obturator prosthesis with magnets, improving appearance and the recovery of significant aspects of the patient's speech and swallowing. Some improvement in mastication was observed., (Copyright © 2022 Editorial Council for The Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.)

Background: Although orbital fractures are common, prediction of outcomes in orbital surgery can be quite challenging., Purpose: We aim to identify predictors of intraoperative difficulty, operating time, and postoperative examination abnormalities in subjects undergoing post-traumatic orbital reconstructions., Study Design, Setting, and Sample: This is a retrospective cohort study of all consecutive orbital operations performed at a private, Level 1 trauma center in Portland, Oregon, USA over an 82-month period. All subjects that underwent exploration of the internal orbit for traumatic indications during the study period were included in the cohort., Predictor Variables: Four plating styles, surgical approach (transorbital vs transantral), days from injury to first surgery, fracture size (approximated as a rectangle using linear measurements from computed tomography scans), anteroposterior fracture position, and medial wall involvement were examined., Outcome Variables: The primary outcome variable was intraoperative difficulty (defined as requiring revision after intraoperative imaging or return to the operating room). Secondary outcome variables included operating time and postoperative examination abnormalities., Covariates: Age and sex were included., Analyses: χ 2 and Regression analyses were performed using a significance level of P < .05., Results: One hundred and sixty four orbital operations were performed (90 isolated injuries and 74 combined orbital/midface injuries) on 155 subjects (73% male, mean age 39.8 years, standard deviation 16.7). In subjects with isolated orbital fractures, medial wall involvement was associated with intraoperative difficulty (P = .01). When using a transantral approach, intraoperative difficulty was more likely in more anterior fractures (P = .02). Plating style was associated with operating time (P = .03), with median times from 81 to 105 minutes (range 21 to 248 minutes). Postoperative examination abnormalities were more likely in the transorbital approach group (P = .01). Neither days to first surgery nor intraoperative difficulty were associated with postoperative examination abnormalities. Postoperative eyelid changes were seen in 13.6% of transorbital approaches and 0% of transantral approaches. Correction of gaze restriction and enophthalmos were more likely than correction of diplopia (P < .01)., Conclusions and Relevance: Medial wall involvement is associated with intraoperative difficulty in orbital surgery. Anteriorly positioned fractures are better treated transorbitally, while posterior fractures may be amenable to transantral repair, thus avoiding risk of lower eyelid changes., (Copyright © 2023 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

Inhibition of monoacylglycerol transferase 2 (MGAT2) has recently emerged as a potential therapeutic strategy for the treatment of metabolic diseases such as obesity, diabetes and non-alcoholic steatohepatitis (NASH). Metabolism studies with our clinical lead (1) suggested variability in in vitro glucuronidation rates in liver microsomes across species, which made projection of human doses challenging. In addition, the observation of deconjugation of the C3-C4 double bond in the dihydropyridinone ring of 1 in solution had the potential to complicate its clinical development. This report describes our lead optimization efforts in a novel pyridinone series, exemplified by compound 33, which successfully addressed both of these potential issues., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Efforts directed at improving potency and preparing structurally different TYK2 JH2 inhibitors from the first generation of compounds such as 1a led to the SAR study of new central pyridyl based analogs 2-4. The current SAR study resulted in the identification of 4h as a potent and selective TYK2 JH2 inhibitor with distinct structural differences from 1a. In this manuscript, the in vitro and in vivo profiles of 4h are described. The hWB IC 50 of 4h was shown as 41 nM with 94% bioavailability in the mouse PK study., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

MGAT2 inhibition is a potential therapeutic approach for the treatment of metabolic disorders. High-throughput screening of the BMS internal compound collection identified the aryl dihydropyridinone compound 1 (hMGAT2 IC 50 = 175 nM) as a hit. Compound 1 had moderate potency against human MGAT2, was inactive vs mouse MGAT2 and had poor microsomal metabolic stability. A novel chemistry route was developed to synthesize aryl dihydropyridinone analogs to explore structure-activity relationship around this hit, leading to the discovery of potent and selective MGAT2 inhibitors 21f , 21s , and 28e that are stable to liver microsomal metabolism. After triaging out 21f due to its inferior in vivo potency, pharmacokinetics, and structure-based liabilities and tetrazole 28e due to its inferior channel liability profile, 21s (BMS-963272) was selected as the clinical candidate following demonstration of on-target weight loss efficacy in the diet-induced obese mouse model and an acceptable safety and tolerability profile in multiple preclinical species.

Purpose: The apnea-hypopnea index (AHI) is the parameter on which the severity of obstructive sleep apnea (OSA) is based and is also the determinant for both clinicians and third-party payers for surgical procedures. The purpose of this retrospective cross-sectional chart review is to examine differences in symptoms and AHI between men and women with OSA and whether this may impact timing and selection of surgical care., Methods: Retrospective cross-sectional study of patients aged 18 years and older who presented at a single center for surgical evaluation of OSA from January 2017 to 2020. AHI, oxygen desaturation index, respiratory disturbance index, and lowest oxygen saturation were obtained from polysomnography. The predictor variable was gender, and the outcome variable was AHI. Unadjusted and multivariate adjusted linear regression models were used to compare differences in AHI between gender, controlling for age, body mass index (BMI), Epworth sleepiness scale, and fatigue severity scale. Poisson regression analysis with robust error was used to assess the relative risks of antidepressant and anxiolytic medication use between genders., Results: A total of 408 consecutive new patients seen for surgical evaluation to treat OSA (248 men and 160 women) were included. Median patient age was 40 years for men and 41 years for women. Median AHI for men was 22.1 events per hour and 13.7 for women (P < .001). When adjusted for age and BMI, men have 33.2% higher AHI than women, with age contributing to 2% and BMI contributing to 6% of the difference. When controlling for age, BMI, Epworth sleepiness scale, and fatigue severity scale, women have a 2.2 increased relative risk of taking anxiolytic or antidepressant medications., Conclusions: Women with OSA seeking surgery in a dedicated sleep practice have 33% lower AHI than men when controlling for age, BMI, and symptoms. Based on our findings, non-gender-specific AHI may handicap the surgeon from offering the full range of available procedures to women with OSA., (Copyright © 2020. Published by Elsevier Inc.)

Dysregulated inflammation following myocardial infarction (MI) promotes left ventricular (LV) remodeling and loss of function. Targeting inflammation resolution by activating formyl peptide receptors (FPRs) may limit adverse remodeling and progression towards heart failure. This study characterized the cellular and signaling properties of Compound 43 (Cmpd43), a dual FPR1/FPR2 agonist, and examined whether Cmpd43 treatment improves LV and infarct remodeling in rodent MI models. Cmpd43 stimulated FPR1/2-mediated signaling, enhanced proresolution cellular function, and modulated cytokines. Cmpd43 increased LV function and reduced chamber remodeling while increasing proresolution macrophage markers. The findings demonstrate that FPR agonism improves cardiac structure and function post-MI., (© 2019 The Authors.)

Fractures of the orbital floor have traditionally been treated through transorbital approaches. Transconjunctival approaches risk entropion, whereas transcutaneous approaches risk ectropion or hypertrophic scarring. The intraoral transantral approach to the orbital floor has the advantage of minimizing the risk of any eyelid changes while providing appropriate access to reduce the herniated orbital contents and restore orbital volume. This article describes 4 plating methods for reconstructing a fractured orbital floor using a transantral approach. Many prior descriptions of transantral treatment of the orbital floor have relied heavily on the use of an endoscope. This article describes an osteotomy technique that does not require an endoscope but requires only a high-quality headlight for visualization., (Copyright © 2019 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: There is increasing interest in developing FPR2 agonists (compound 43, ACT-389949 and BMS-986235) as potential pro-resolving therapeutics, with ACT-389949 and BMS-986235 having entered phase I clinical development. FPR2 activation leads to diverse downstream outputs. ACT-389949 was observed to cause rapid tachyphylaxis, while BMS-986235 and compound 43 induced cardioprotective effects in preclinical models. We aim to characterise the differences in ligand-receptor engagement and downstream signalling and trafficking bias profile., Experimental Approach: Concentration-response curves to G protein dissociation, β-arrestin recruitment, receptor trafficking and second messenger signalling were generated using FPR2 ligands (BMS-986235, ACT-389949, compound 43 and WKYMVm), in HEK293A cells. Log(τ/K A ) was obtained from the operational model for bias analysis using WKYMVm as a reference ligand. Docking of FPR2 ligands into the active FPR2 cryoEM structure (PDBID: 7T6S) was performed using ICM pro software., Key Results: Bias analysis revealed that WKYMVm and ACT-389949 shared a very similar bias profile. In comparison, BMS-986235 and compound 43 displayed approximately 5- to 50-fold bias away from β-arrestin recruitment and trafficking pathways, while being 35- to 60-fold biased towards cAMP inhibition and pERK1/2. Molecular docking predicted key amino acid interactions at the FPR2 shared between WKYMVm and ACT-389949, but not with BMS-986235 and compound 43., Conclusion and Implications: In vitro characterisation demonstrated that WKYMVm and ACT-389949 differ from BMS-986235 and compound 43 in their signalling and protein coupling profile. This observation may be explained by differences in the ligand-receptor interactions. In vitro characterisation provided significant insights into identifying the desired bias profile for FPR2-based pharmacotherapy., (© 2024 The Author(s). British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Purpose: The purpose of this study was to analyze maxillofacial trauma sustained by patients at least 75 years old. With the injury patterns identified, treatment recommendations for the contemporary oral and maxillofacial surgeon are made., Patients and Methods: This study was a retrospective case series using data from 2 level 1 trauma centers. The variables of interest included age at traumatic event, gender, mechanism of trauma, concomitant injuries, radiographic studies performed, management of maxillofacial injuries, and disposition. Numerical analysis was completed with statistical software., Results: One hundred seventy-six patients at least 75 years old who sustained facial trauma were identified. Ground-level falls caused most cases of maxillofacial trauma in the geriatric population. The median age at the time of trauma was 83 and 85 years for men and women, respectively. The most common injuries were midface fractures. Intracranial hemorrhage was the most common concomitant injury, and all but 1 patient underwent computed tomography of at least the head after their traumatic event. Most maxillofacial injuries were treated without operative repair., Conclusions: The information gained from this study suggests that oral and maxillofacial surgeons should counsel geriatric patients on the risk of falls and encourage the prevention of potential hazards for falls in their homes., (Copyright © 2018. Published by Elsevier Inc.)

Background: Retrospective analysis of post-operative vomiting (POV) in non-human primates at our institution was 11%. Based on this additional risk factor for post-operative complications, we aimed to eliminate or decrease POV by adding an antiemetic, maropitant citrate, to the pre-medication protocol., Methods: Retrospective and prospective data were collected over a 5-year period from 46 macaques of two species during 155 procedures. Additionally, blood was collected from five Macaca mulatta to perform a pharmacokinetic analysis., Results: A 1 mg/kg subcutaneous dose of maropitant given pre-operatively significantly decreased POV. Findings indicated post-neurosurgical emesis in Macaca fasicularis was significantly greater than in Macaca mulatta. Pharmacokinetic analysis of maropitant in Macaca mulatta determined the mean maximum plasma concentration to be 113 ng/mL., Conclusions: Maropitant administration prior to anesthesia for neurosurgeries decreased our incidence of POV to 1%. The plasma concentration reaches the proposed plasma level for clinical efficacy approximately 20 minutes after administration., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The placement of a resorbable suture on one edge of a wound can effectively retard the mucosal closure of the defect and thereby duplicate the function of a passive surgical drain. The placement of a double or triple loop of a resorbable suture such as chromic gut on one side of the wound edge can provide an inexpensive and self-eliminating wound drain., (Copyright © 2016 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

This study explores the efficacy of texture analysis by using preoperative multi-slice spiral computed tomography (MSCT) to non-invasively determine the grade of cellular differentiation in head and neck squamous cell carcinoma (HNSCC). In a retrospective study, MSCT scans of patients with HNSCC were analyzed and classified based on its histological grade as moderately differentiated, well-differentiated, or poorly differentiated. The location of the tumor was categorized as either in the bone or in soft tissues. Segmentation of the lesion areas was conducted, followed by texture analysis. Eleven GLCM parameters across five different distances were calculated. Median values and correlations of texture parameters were examined in relation to tumor differentiation grade by using Spearman's correlation coefficient and Kruskal–Wallis and Dunn tests. Forty-six patients were included, predominantly female (87%), with a mean age of 66.7 years. Texture analysis revealed significant parameter correlations with histopathological grades of tumor differentiation. The study identified no significant age correlation with tumor differentiation, which underscores the potential of texture analysis as an age-independent biomarker. The strong correlations between texture parameters and histopathological grades support the integration of this technique into the clinical decision-making process. [ABSTRACT FROM AUTHOR]

Background: This multicenter study was undertaken to characterize the metastatic behavior of oral maxillary squamous carcinoma and to determine the role of selective neck dissection., Methods: A retrospective, multicenter study of patients surgically treated for oral maxillary squamous carcinoma was completed. Data collected included primary tumor location, cervical lymph node status, and neck failure rate., Results: The study included 146 patients. The adjusted regional metastatic rate was 31.4%. Of those N0 (clinically negative) necks treated with or without neck dissection, 14.4% developed cervical metastasis. Within the cohort, 7.5% of patients died with distant disease. The regional salvage rate was 52.9%. None of the patients with locoregional failures were salvaged., Conclusions: Maxillary palatal, alveolar, and gingival squamous carcinomas exhibit aggressive regional metastatic behavior. Surgical salvage rates for neck failure are low; therefore, selective neck dissection (levels I-III) is recommended at the time of resection of T2, T3, and T4 maxillary squamous carcinomas., (Copyright © 2010 Wiley Periodicals, Inc.)

Purpose: Although rare, there are many circumstances in which a secure airway is needed urgently. A newly developed technique is presented for quick and efficient performance of this procedure., Patients and Methods: All patients who had tracheotomies performed at a tertiary referral center from January 1, 2004, through December 31, 2008, were found by querying the admission database. Three hundred twenty-seven separate procedures performed in 325 patients were identified. Urgent tracheotomies were distinguished from elective and emergent tracheotomies by reading operative reports and excluding elective and emergent procedures. Elective procedures were defined as performed in patients with a secure airway (with an endotracheal tube or laryngeal mask airway). Urgent tracheotomies were defined as having an intact, unprotected airway. Emergent procedures were performed in a patient with complete airway obstruction., Results: Twenty instances of urgent, awake tracheotomies were found in 19 patients, resulting in an incidence of 20 of 327 tracheotomies (6.1%) in 19 of 325 patients (5.8%)., Conclusions: Tracheotomy is an alternative to cricothyroidotomy as a surgical airway in patients with deteriorating respiratory status who cannot be safely intubated by nonsurgical means., (Copyright © 2011 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

Introduction: We report our experience in the treatment of parotid cancers by radiotherapy delivered with curative intent over a period of 10 years. Aim: The aim of this study was to evaluate the therapeutic results and prognostic factors. Materials and methods: This is a retrospective study of patients with parotid cancer treated with radiotherapy between 2008 and 2017 at the National Institute of Oncology in Rabat. Patients who received adjuvant or exclusive radiotherapy were included in this study. We performed a multivariate analysis for the factors related to locoregional control and overall survival. Results: Initially, 74 patients (45 men and 29 women), at a median age of 57 years. were identified. At the time of diagnosis, 10 (13.6%), 36 (48.6%), and 28 (37.8%) patients were in stage II, III, and IVab, respectively. Sixty patients received adjuvant radiotherapy after parotidectomy and 14 patients received exclusive radiotherapy for an unresectable tumor. At 5 years, the rate of locoregional control and overall survival were 68.2% and 53.7%, respectively. Surgical resection and negative margins were significantly correlated with locoregional control. Lymph node involvement, unresectable tumors, high-grade histological types, and cystic adenoid carcinoma were significantly correlated with poor overall survival. Conclusions: Acceptable long-term results are obtained with surgery combined with radiotherapy. Surgical resection remains essential for parotid cancer, given the disappointing results of treatment with radiotherapy alone. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this retrospective study was to review the outcome of patients with oral cavity squamous cell carcinoma treated at a single institution by primary surgical resection with or without adjuvant radiotherapy or chemoradiotherapy and to identify factors affecting survival and locoregional control., Patients and Methods: The records of 233 patients with oral cavity squamous cell carcinoma treated at a single institution from 1993 to 2003 were identified from the Legacy Emanuel Hospital and Health Center's cancer registry (Portland, OR). All patients undergoing surgical resection as a primary treatment modality were included in the study. Patients with nonresectable disease, distant metastasis, and those with inadequate follow-up data were excluded from the study. Patients with positive surgical margins, high-grade histology, aggressive biologic behavior, or advanced staged disease underwent adjuvant radiotherapy or chemoradiotherapy. The data collected included age, gender, race, tumor site, margin status, grade, TNM stage, cancer therapies, and cancer status. Data were statistically analyzed in an attempt to identify predictors of locoregional control and disease-free survival. Descriptive statistics were calculated for each variable and survival was calculated using the Kaplan-Meier method. Prognostic factors were analyzed using the Cox proportional hazard model., Results: Two hundred fifteen patients consisting of 119 men (55%) and 123 females (52%), with an average age at diagnosis of 66 years (SD +/- 14), met the criteria for inclusion in the study. Average tumor size was 23.5 mm (SD +/- 14.1). Overall 5-year survival was 56% and disease-free survival at 5 years was 58%. Stage and grade were identified as having a statistically significant effect on survival (P = .014; likelihood ratio chi-square = 10.7, 3 degrees of freedom; and P = .026; likelihood ratio chi-square = 5, 1 degree of freedom, respectively). Neither age, gender, race, tumor site, nor positive margins showed a statistically significant effect on survival (P > .05)., Conclusion: This study highlights the importance of grade and stage as independent factors in predicting survival in patients with oral squamous cell carcinoma.

Purpose: The purpose of this study was to analyze trauma patients, ages 55 and older, sustaining multiple injuries including maxillofacial trauma. Factors influencing length of intensive care unit stay (ICUS) and length of total hospital stay were delineated and examined to determine if specific causes of increased length of stay could be elucidated, and, once known, if these causes could translate into recommendations tailored to the oral and maxillofacial surgery trauma practice., Patients and Methods: One hundred ninety-six patients, 55 years of age or older, who received either consultation alone, or consultation with surgical treatment, by oral and maxillofacial surgeons, from January 1991 to August 1998 were included in this study. Variables of interest included location of traumatic event, mechanism of injury, patient age and gender, comorbidities on presentation, Injury Severity Score (ISS), specific injuries incurred, ICUS, length of hospital stay (LOS), surgical interventions, and disposition., Results: Complications were the statistically significant factor determining length of ICU stay. ICUS, complications incurred, and ISS were the important predictors of total LOS. The significant complications affecting LOS were infectious, respiratory, and hematologic complications., Conclusion: The number of complications the patient incurs after an injury can predict length of ICUS. Length of ICUS, ISS, and number of complications incurred were the strongest predictors for total length of hospital stay. Other variables, including age, gender, living or dead, blunt versus penetrating injury, ISS, fracture site (skull, midface, or lower face), and comorbidities on presentation were not statistically significant in this patient population. Infectious, respiratory, and hematologic complications were the complications most closely correlated with increasing length of ICUS and total hospital stay., (Copyright 2002 American Association of Oral and Maxillofacial Surgeons)

Objective: To validate the use of temperature-controlled radiofrequency energy applied to the soft palate in a multicenter setting for reduction of snoring in a minimally morbid manner., Methods: Prospective, nonrandomized multicenter study of 113 patients who had a respiratory disturbance index less than 15 and minimum oxygen saturation not less than 85% and who were seeking treatment for habitual disruptive snoring. Patients were given either single or multiple lesions to the soft palate during each treatment session., Results: Patients received 1978 J on average with an overall average of 2.4 treatments. Snoring scores went from an average of 7.8 (visual analog scale (VAS), 0-10) pretreatment to 3.2 posttreatment. Pain was minimal, averaging 1.7 (VAS 0-10) on days 1 to 6. Complications were few and transient, and mild., Conclusions: The multiple lesion protocol was the most successful; reducing snoring from 7.6 to 2.7, on a VAS with an average of 1232 J delivered over 1.6 treatments. Temperature-controlled radiofrequency was found to be a minimally invasive, well-tolerated procedure that was safe and efficacious in this study group.

The transoral approach to open reduction of mandibular fractures has gained popularity but remains controversial. This report reviews 37 consecutive transoral open reductions of various mandibular fractures performed in 32 patients over a 2-year period. The fracture site most often addressed transorally was the symphysis and parasymphysis area. A 19% complication rate and an 11% infection rate were observed. [ABSTRACT FROM AUTHOR]

Numerous approaches to the orbit have been elegantly described in the literature. One area of the orbit that remains difficult to approach with standard techniques is the inferonasal apex. We describe a new surgical procedure we have termed the LeFort I orbitotomy. The technique involves creation of a LeFort I osteotomy to separate the maxilla from the zygoma and nose bilaterally. The posterior inferomedial orbital bone is then removed and the periorbita opened. This approach allows a more direct, less tangential view to this area of the orbit than does a Caldwell-Luc approach. Wider access for tumor manipulation is gained than would be possible with a transnasal endoscopic approach. An illustrative case report is presented.

Background: Vascularized free tissue transfer has been established as an effective method in the reconstruction of mandibular defects. However, a limited understanding of its efficacy in pediatric patients persists due to its infrequent presentation. The aim of this study is to systematically consolidate the survival and infection rates of free flaps in pediatric mandibular reconstruction., Methods: A systematic literature search was conducted on Ovid Medline, Embase, and Cochrane Library for studies published up to January 2024. We included peer-reviewed studies reporting on survival and infection outcomes associated with free flap mandibular reconstruction in pediatric patients (<18 years). We performed a random-effects meta-analysis with the inverse-variance weighted approach to estimate survival and infection rates. Heterogeneity was assessed by I 2 , and publication bias was examined using Egger's test., Results: A total of 26 studies, reporting on 463 free flaps and 439 pediatric patients with a mean age of 10.7 years, were included in our study. Most free flaps originated from the fibula (n = 392/463, 84.7%) and benign tumors were the most common cause for mandibular reconstruction (n = 179/463, 38.7%). The pooled estimate for survival of flaps was 96% (95% CI: 93-97, I 2  = 0%), and recipient-site infections were estimated to occur in 9% (95% CI: 6-13, I 2  = 0%) of cases. The most common reported complications within the study timeframe were early malocclusion (n = 28/123, 21.4%) and bite abnormalities (18/131, 13.7%)., Conclusion: Free tissue transfer for mandibular reconstruction in pediatric patients is effective and safe. Further research is required to explore functionality following mandibular reconstruction in diverse pediatric populations., (© 2024 The Author(s). Microsurgery published by Wiley Periodicals LLC.)

Heart failure remains a leading cause of morbidity and mortality worldwide. Current treatment for patients with heart failure include drugs targeting G protein-coupled receptors such as β-adrenoceptor antagonists (β-blockers) and angiotensin II type 1 receptor antagonists (or angiotensin II receptor blockers). However, many patients progress to advanced heart failure with persistent symptoms, despite treatment with available therapeutics that have been shown to reduce mortality and mortality. GPCR targets currently being explored for the development of novel heart failure therapeutics include adenosine receptor, formyl peptide receptor, relaxin/insulin-like family peptide receptor, vasopressin receptor, endothelin receptor and the glucagon-like peptide 1 receptor. Many GPCR drug candidates are limited by insufficient efficacy and/or dose-limiting unwanted effects. Understanding the current challenges hindering successful clinical translation and the potential to overcome existing limitations will facilitate the future development of novel heart failure therapeutics. LINKED ARTICLES: This article is part of a themed issue Therapeutic Targeting of G Protein-Coupled Receptors: hot topics from the Australasian Society of Clinical and Experimental Pharmacologists and Toxicologists 2021 Virtual Annual Scientific Meeting. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v181.14/issuetoc., (© 2023 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

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Eighty percent of cerebrospinal fluid leaks (CSF) occur following trauma and complicate 12 to 13% percent of all basilar skull fractures (Prosser, Vender, and Solares, 2011). An endoscopic endonasal approach (EEA) is often the preferred method of repair with greater than 90% success rates (Prosser, Vender, and Solares, 2011). We report a case of a 37-year-old man who presented to our regional level 1 trauma centre with multiple facial injuries. Initial cross-sectional imaging revealed multiple, continuous anterior skull base fractures with associated pneumocephalus. Though initially managed conservatively, the patient represented five days later with unilateral left-sided rhinorrhoea. An endoscopic endonasal repair with a multilayer fat, tensor fascia lata, free mucosal graft, and vascularised local flap reconstruction was undertaken. This case highlights the importance of maintaining a high level of suspicion for delayed CSF leak in traumatic base of skull injury. The EEA enables meticulous dissection and thorough inspection of the skull base, facilitating multilayered repair and reconstruction of defects. [ABSTRACT FROM AUTHOR]

Aim: Oral cancer is one of the top three types of cancer and is of significant public health importance in India. A common post-translational modification in cells is ubiquitination/deubiquitination, and its dysregulation is closely associated with the development of cancer. Studies on the role of ubiquitination in oral squamous cell carcinoma (OSCC) are lacking. Increased expression of usp36 has been observed in various types of cancer, and this study aimed to check the gene expression of usp36 in OSCC patients. In this study, we analyzed the expression of ubiquitin-specific proteases (USPs) 36 in OSCC. Materials and Methods: A total of 15 OSCC patients at different stages of tumor differentiation and age- and sex-matched controls were recruited for the study. The patients were categorized based on their differentiation patterns. RNA was extracted from the tissues, and usp36 gene expression was checked in these samples using a quantitative real-time PCR technique. Results: Our study showed increased expression of usp36 gene in OSCC patients. The usp36 mRNA was 231.8 ± 137.94 folds higher in well-differentiated squamous cell carcinoma patients, 38.18 ± 3.77 folds higher in moderately differentiated squamous cell carcinoma patients, and 25.49 ± 7.30 folds higher in poorly differentiated squamous cell carcinoma patients compared to control tissues. Conclusion: Our study reports, for the first time, an increased gene expression of usp36 in OSCC tissues. [ABSTRACT FROM AUTHOR]