Speciation of Technetium Dibutylphosphate in the Third Phase Formed in the TBP/HNO3 Solvent Extraction System.

The speciation of technetium in the nitric acid/dibutylphosphoric acid (HDBP)-n-dodecane system was studied by extended X-ray absorption fine structure (EXAFS) spectroscopy and theoretical methods. Tetravalent technetium, produced by the hydrazine reduction of TcO4- in 3 M HNO3, was extracted by HDBP in n-dodecane (30% by volume). During extraction, the splitting of the organic phase into a heavy phase and a light phase was observed. EXAFS analysis is consistent with the presence of Tc(NO3)3(DBP)(HDBP)2 in the light phase and Tc(NO3)2(DBP)2(HDBP)2 in the heavy phase. Density functional theory calculations at the B3LYP/6-31G* level confirm the stability of the proposed species and indicate that stereoisomers -mer- and fac-Tc(NO3)3(DBP)(HDBP)2 for the light phase and cis- and trans-Tc(NO3)2(DBP)2(HDBP)2 for the heavy phase] could coexist in the system (in the n-dodecane solution). Mechanisms of formation of Tc(NO3)3(DBP)(HDBP)2 and Tc(NO3)2(DBP)2(HDBP)2 are proposed.

Modified cadaver technique to simulate contaminated airway scenarios to train medical providers in suction-assisted laryngoscopy and airway decontamination.

Simulation training plays a vital role in modern medical education, fostering safe skill development. Task-trainer manikin and cadaveric airway management training (CAMT) offer realistic airway management practice. Simulation allows learners the opportunity to manage high-risk, low-frequency scenarios, including difficult airways and massive airway contamination, common in emergent airway management. The suction-assisted laryngoscopy and airway decontamination (SALAD) technique was developed to address massive airway contamination. This paper describes two methods to simulate massive airway contamination utilizing cadavers. We detail our techniques for both esophageal and nasopharyngeal delivery of simulated airway contaminant. Nasopharyngeal delivery was less invasive and required less time to set up. Utilizing cadavers to simulate massive airway contamination in CAMT provides learners with tools to manage airway complications effectively, enhancing readiness for complex airway challenges while promoting patient safety in clinical practice.

Prognostic risk factors of buccal squamous cell carcinoma: A case-control study.

OBJECTIVES: To describe the clinicopathologic presentation of buccal squamous cell carcinoma and identify risks factors for recurrence and overall survival. METHODS: This is a retrospective case-control study of patients with oral cavity squamous cell carcinoma (OCSCC) treated at a single tertiary care center between 2010 and 2022. All patients with buccal subsite OCSCC treated during this time frame were included and paired with a randomly selected age and gender matched patient with non-buccal OCSCC. Relevant data was collected via chart review. RESULTS: Seventy-seven patients with buccal SCC were matched with 77 non-buccal OCSCC controls. The median follow-up time was 27 months (IQR 14-61). Median age was 67 years (IQR 57-75) and 53% of the cohort was female. Twenty (26%) buccal SCC patients experienced a recurrence versus 19 (25%) in the controls. Age ≥65-years-old increased odds of all-cause mortality in the buccal SCC group, but not in the control group. Perineural invasion and positive margins increased odds of recurrence in the buccal group only. Overall survival and progression-free survival did not differ between the groups, despite a greater number of T2 buccal tumors and T1 non-buccal tumors. CONCLUSIONS: Buccal SCC presents at a higher T stage than other oral cavity SCC subsite and may exhibit variance in the pathologic risk factors that predict poor outcomes versus non-buccal OCSCC. Despite these relatively minor differences, however, oncologic outcomes between these groups were similar.

The neutrophil-to-lymphocyte ratio in salivary gland cancers treated with pembrolizumab.

BACKGROUND: A minority of patients with recurrent/metastatic (R/M) salivary gland cancers (SGCs) benefit from immune checkpoint inhibitors (ICIs), necessitating reliable biomarkers for ICI response prediction. METHODS: Retrospective observational study of R/M SGC patients treated with pembrolizumab between 2016 and 2022, with a primary outcome of 6-month progression-free survival (PFS) and secondary outcome of 2-year overall survival (OS). Univariate and multivariable Cox proportional hazards models were employed. RESULTS: Twenty R/M SGC patients were included. After adjustment, NLR as a continuous variable was independently associated with 6-month PFS (HR 1.30, 95% CI 1.10-1.54, p = 0.002) and 2-year OS (HR 1.33, 95% CI 1.07-1.66, p = 0.010). Similarly, NLR ≥ 5 was associated with higher hazards of progression at 6 months (HR 12.85, 95% CI 2.17-76.16, p = 0.005) and death at 2 years (HR 11.25, 95% CI 1.67-75.77, p = 0.013). CONCLUSIONS: Higher pretreatment NLR was independently associated with inferior 6-month PFS and 2-year OS in pembrolizumab-treated R/M SGC patients.

Structural Investigation of Technetium Dibutylphosphate Species Using X-ray Absorption Fine Structure Spectroscopy.

The speciation of Tc after the extraction of Tc(IV) from H2O and 1 M HNO3 by dibutylphosphoric acid (HDBP) in dodecane has been studied by X-ray absorption fine structure (XAFS) spectroscopy. Results show the formation of dimeric species with Tc2O2 and Tc2O units, and the formulas [Tc2O2(DBP·HDBP)4] (1) and [Tc2O(NO3)2(DBP)2(DBP·HDBP)2] (2) were, respectively, proposed for the species extracted from H2O and 1 M HNO3. The interatomic Tc-Tc distances found in the Tc2O2 and Tc2O units [2.55(3) and 3.57(4) Å, respectively] are similar to the ones found in Tc(IV) dinuclear species. It is likely that the speciation of Tc(IV) in dodecane is due to the extraction of a species with a Tc2O unit for (2) and to the redissolution of a Tc(IV)-DBP solid for (1). The XAFS results for (1) and (2) were compared to that obtained for the extraction of Tc(IV) with TBP/HDBP/dodecane from 0.5 M HNO3, (3) which highlight the formation of Tc mononuclear nitrate species {i.e., [Tc(NO3)3(DBP)] or [Tc(NO3)2(DBP·HDBP)]}. These results confirm the importance of the preparation and speciation of the Tc(IV) aqueous solutions prior to extraction and how much this influences and drives the final Tc speciation in organic extraction. These studies outline the complexity of Tc separation chemistry and provide insights into the behavior of Tc during the reprocessing of used nuclear fuel.

Bioinspired Total Synthesis of Hyperireflexolides A and B.

Hyperireflexolides A and B were synthesized in six steps via the dearomatization and fragmentation of a simple acylphloroglucinol starting material. The dearomatized acylphloroglucinol undergoes a sequence of oxidative radical cyclization, retro-Dieckmann fragmentation, stereodivergent intramolecular carbonyl-ene reactions, and final α-hydroxy-ß-diketone rearrangements to give the target natural products. This sequence is based on a biosynthetic proposal that claims the hyperireflexolides as highly rearranged polycyclic polyprenylated acylphloroglucinols (PPAPs), which is supported by the structural revision of hyperireflexolide B.

A bioinspired, one-step total synthesis of peshawaraquinone.

A concise synthesis of a stereochemically complex meroterpenoid, peshawaraquinone, via the unsymmetrical dimerization of its achiral precursor, dehydro-α-lapachone, is reported. Enabled by reversible oxa-6π-electrocyclizations of 2H-pyran intermediates, the base-catalyzed dimerization sets up an intramolecular (3 + 2) cycloaddition, with the formation of six stereocenters during the cascade. Combining the generation and in situ dimerization of dehydro-α-lapachone allows a one-step total synthesis of peshawaraquinone from lawsone and prenal.

Patterns of Postoperative Trismus Following Mandibulectomy and Fibula Free Flap Reconstruction.

The factors that contribute to postoperative trismus after mandibulectomy and fibula free flap reconstruction (FFFR) are undefined. We retrospectively assessed postoperative trismus (defined as a maximum interincisal opening ≤35 mm) in 106 patients undergoing mandibulectomy with FFFR, employing logistic regression to identify risk factors associated with this sequela. The surgical indication was primary ablation in 64%, salvage for recurrence in 24%, and osteonecrosis in 12%. Forty-five percent of patients had existing preoperative trismus, and 58% of patients received adjuvant radiation/chemoradiation following surgery. The overall rates of postoperative trismus were 76% in the early postoperative period (≤3 months after surgery) and 67% in the late postoperative period (>6 months after surgery). Late postoperative trismus occurred more frequently in patients with ramus-involving vs. ramus-preserving posterior mandibulotomies (82% vs. 46%, p = 0.004). A ramus-involving mandibulotomy was the only variable significantly associated with trismus >6 months postoperatively on multivariable logistic regression (OR, 7.94; 95% CI, 1.85−33.97; p = 0.005). This work demonstrates that trismus is common after mandibulectomy and FFFR, and suggests that posterior mandibulotomies that involve or remove the ramus may predispose to a higher risk of persistent postoperative trismus.

Total Synthesis of Atrachinenins A and B.

Inspired by a new biosynthetic hypothesis, we report a biomimetic total synthesis of atrachinenins A and B that explains their racemic nature. The synthesis exploits an intermolecular Diels-Alder reaction between a quinone meroterpenoid and E-ß-ocimene, followed by intramolecular (3 + 2) cycloaddition and a late-stage aerobic oxidation. Divergent transformations of a simple model system gave several complex polycyclic scaffolds, while also suggesting a structure revision for atrachinenin C.

Structural Basis of Stereospecific Vanadium-Dependent Haloperoxidase Family Enzymes in Napyradiomycin Biosynthesis.

Vanadium-dependent haloperoxidases (VHPOs) from Streptomyces bacteria differ from their counterparts in fungi, macroalgae, and other bacteria by catalyzing organohalogenating reactions with strict regiochemical and stereochemical control. While this group of enzymes collectively uses hydrogen peroxide to oxidize halides for incorporation into electron-rich organic molecules, the mechanism for the controlled transfer of highly reactive chloronium ions in the biosynthesis of napyradiomycin and merochlorin antibiotics sets the Streptomyces vanadium-dependent chloroperoxidases apart. Here we report high-resolution crystal structures of two homologous VHPO family members associated with napyradiomycin biosynthesis, NapH1 and NapH3, that catalyze distinctive chemical reactions in the construction of meroterpenoid natural products. The structures, combined with site-directed mutagenesis and intact protein mass spectrometry studies, afforded a mechanistic model for the asymmetric alkene and arene chlorination reactions catalyzed by NapH1 and the isomerase activity catalyzed by NapH3. A key lysine residue in NapH1 situated between the coordinated vanadate and the putative substrate binding pocket was shown to be essential for catalysis. This observation suggested the involvement of the ε-NH2, possibly through formation of a transient chloramine, as the chlorinating species much as proposed in structurally distinct flavin-dependent halogenases. Unexpectedly, NapH3 is modified post-translationally by phosphorylation of an active site His (τ-pHis) consistent with its repurposed halogenation-independent, α-hydroxyketone isomerase activity. These structural studies deepen our understanding of the mechanistic underpinnings of VHPO enzymes and their evolution as enantioselective biocatalysts.

Caught on camera: a video assessment of suspected concussion and other injury events in women's rugby union.

OBJECTIVES: The objective of this study was to identify and report the incidence and mechanisms of suspected injury and concussion in women's rugby union. DESIGN: A cross-sectional video analysis study. METHODS: Using video analysis of non-professional, single-angle footage, cases of suspected injury and concussion were identified and reported, based on content validation and consensus by eight rugby-specific researchers, therapists, and sport medicine physicians. RESULTS: There were 225 suspected injuries recorded in 48 games [Suspected injury rate (IR) = 117.5/1000 h (95 % CI;102.6-133.9) or 4.7 suspected injuries per match]. The on-field medical attention IR was 95.0/1000 h (95 % CI;81.7-109.9: 3.8 per game). Suspected concussions accounted for 26 % of injuries (30.8/1000 h: 95 % CI;23.5-39.7: 1.2 per game). The attacking team sustained 64 % of suspected injuries. Permanent removal from play was observed for 29 % of suspected injuries. The most common suspected injury locations were head/neck (28.4 %) and lower extremity (27.6 %). The tackle accounted for 67.1 % of all suspected injuries, with a propensity of 11.2/1000 tackle events (95 % CI;9.5-13.2) or 3.1 tackle-related injuries/game. Of tackle-related injuries, 63.6 % were to the ball carrier while 52.2 % of tackle-related concussions were to the ball carrier. CONCLUSION: This study adds to the growing body of literature examining women's rugby. The rate of suspected injury is high compared with other studies. It is acknowledged that these are suspected injuries not supported by prospective injury surveillance. The high proportion of suspected injuries that are tackle-related warrants specific attention to identify tackle characteristics associated with injury and concussion.

Intramolecular Tricarbonyl-Ene Reactions and α-Hydroxy-ß-Diketone Rearrangements Inspired by the Biosynthesis of Polycyclic Polyprenylated Acylphloroglucinols.

Structurally unique natural products pose biosynthetic puzzles whose solution can inspire new chemical reactions. Herein, we propose a unified biosynthetic pathway towards some complex meroterpenoids-the hyperireflexolides, biyoulactones, hybeanones and hypermonones. This hypothesis led to the discovery of uncatalyzed, intramolecular carbonyl-ene reactions that are spontaneous at room temperature. We also developed an anionic cascade reaction featuring an α-hydroxy-ß-diketone rearrangement and an intramolecular aldol reaction to access four distinct natural product scaffolds from a common intermediate.

Biomimetic synthesis of the non-canonical PPAP natural products yezo'otogirin C and hypermogin D, and studies towards the synthesis of norascyronone A.

Oxidative degradation and rearrangement of polycyclic polyprenylated acylphloroglucinols (PPAPs) has created diverse families of unique natural products that are attractive targets for biomimetic synthesis. Herein, we report a racemic synthesis of hyperibrin A and its oxidative radical cyclization to give yezo'otogirin C, followed by epoxidation and House-Meinwald rearrangement to give hypermogin D. We also investigated the biomimetic synthesis of norascyronone A via a similar radical cyclization pathway, with unexpected results that give insight into its biosynthesis.

Bioinspired Total Synthesis of Erectones A and B, and the Revised Structure of Hyperelodione D.

The field of biomimetic synthesis seeks to apply biosynthetic hypotheses to the efficient construction of complex natural products. This approach can also guide the revision of incorrectly assigned structures. Herein, we describe the evolution of a concise total synthesis and structural reassignment of hyperelodione D, a tetracyclic meroterpenoid derived from a Hypericum plant, alongside some biogenetically related natural products, erectones A and B. The key step in the synthesis of hyperelodione D forms six stereocentres and three rings in a bioinspired cascade reaction that features an intermolecular Diels-Alder reaction, an intramolecular Prins reaction and a terminating cycloetherification.

A Diazo-Hooker Reaction, Inspired by the Biosynthesis of Azamerone.

Motivated by the biosynthesis of azamerone, we report the first example of a diazo-Hooker reaction, which involves the formation of a phthalazine ring system by the oxidative rearrangement of a diazoketone. Computational studies indicate that the diazo-Hooker reaction proceeds via an 8π-electrocyclization followed by ring contraction and aromatization. The biosynthetic origin of the diazoketone functional group was also chemically mimicked using a related natural product, naphterpin, as a model system.

Impact of Smoking and Primary Tumor Subsite on Recurrence in HPV-Associated Oropharyngeal Squamous Cell Carcinoma.

OBJECTIVE: To describe risk of recurrence and recurrence characteristics between ever- and never-smoking patients with human papillomavirus-associated oropharyngeal squamous cell carcinoma (HPV+ OPSCC) when stratified by primary tumor subsite. STUDY DESIGN: Retrospective observational study. SETTING: Tertiary care center. METHODS: Retrospective chart review of 171 patients with HPV+ OPSCC with primary treatment between 2008 and 2019. Five-year recurrence-free survival and risk of recurrence were evaluated through Kaplan-Meier curves with log-rank test and Cox proportional hazards models, respectively. RESULTS: Of 171 patients with HPV+ OPSCC, 81.9% were male, and the average age was 63.9 years. Eighty patients (46.8%) had a smoking history (average, 17.7 pack-years), including 4 current smokers. Recurrence occurred in 31 patients (18.1%), 19 of whom were ever smokers. The recurrence rate for ever smokers with primary base of tongue (BOT) cancer was 41.7%, while 5.1% of never smokers with BOT primaries had recurrence. For primary tonsillar disease, 9.1% of ever smokers had recurrence versus 19.2% of never smokers. Five-year recurrence-free survival for BOT primaries was lower in ever smokers than never smokers (P = .001) but did not differ between ever and never smokers for tonsillar primaries (P = .215). In multivariable analysis across this period, ever-smoking status was associated with higher risk of recurrence than never-smoking status in BOT primaries (adjusted hazard ratio, 7.36; 95% CI, 1.61-33.68; P = .010) but with lower risk of recurrence after tonsillar primaries (adjusted hazard ratio, 0.23; 95% CI, 0.06-0.89; P = .033). CONCLUSION: Smoking may uniquely interact with tumor subsites within the oropharynx to influence recurrence risk. Understanding the association between smoking and HPV+ OPSCC recurrence could lead to personalized, evidence-based treatments to improve oncologic outcomes.

Adenosine deaminase, not immune to a mechanistic rethink in central nervous system disorders?

Adenosine deaminase (ADA) is a purine metabolism enzyme that catalyses the breakdown of adenosine and deoxyadenosine. The enzyme is important in several cellular processes, including the innate immune response and cellular differentiation, and it is also an important enzyme for the maintenance of brain homeostasis, in part due to its regulation of adenosine. Aberrant regulation of ADA enzyme activity has been linked to several neurodegenerative diseases and diseases that can result in neurological impairment. However, the mechanisms behind altered ADA regulation and how this leads to the development of neurological dysfunction are poorly characterised. This review summarises the current research on ADA and its role and regulation in disease pathology, with a focus on the central nervous system (CNS) and the neurodegenerative disease, amyotrophic lateral sclerosis (ALS).

Adjuvant therapy improves survival in pT4aN0 oral cavity squamous cell carcinoma with bone invasion.

OBJECTIVE: The prognostic significance of bone invasion in oral cavity squamous cell carcinoma (OCSCC) after accounting for tumor size, nodal spread, and surgical margins is controversial. The aim of this study is to determine whether patients with pT4aN0 oral cavity squamous cell carcinoma with bone invasion have improved overall and disease-free survival with adjuvant treatment. METHODS: We conducted a retrospective review of medical records from 64 patients with stage pT4aN0 due to mandibular involvement who underwent surgery from 2000 to 2020. Kaplan-Meier analysis compared disease-free survival and overall survival between groups who underwent surgery only versus surgery and adjuvant therapy. The prognostic impact of adjuvant therapy was assessed using multivariate analysis and reported as hazard ratios. RESULTS: There were no statistically significant differences in clinicopathologic features or mean follow-up between patients who received surgery only and patients who received surgery with RT/CCRT (radiotherapy/concurrent chemoradiation therapy). 5-year disease-free (42.5% versus 65.9%, p = 0.02) and overall survival (43.6% versus 69.0%, p = 0.014) were improved in groups who received surgery and RT/CCRT. Regression analysis controlling for clinicopathologic characteristics, including tumor size, identified radiation as an independent predictor of improved disease-free survival (HR: 0.04, p < 0.001) and overall survival (HR: 0.10, p < 0.001). CONCLUSION: Adjuvant RT/CCRT in patients with pT4N0 OCSCC with mandibular bone involvement is associated with improved disease-free and overall survival. This association was significant regardless of tumor pathologic features such as size or margin status. These findings may help guide physicians in counseling patients regarding risks and benefits of adjuvant RT/CCRT and inform practice guidelines.

Should Sentinel Lymph Node Biopsy Status Guide Adjuvant Radiation Therapy in Patients With Merkel Cell Carcinoma?

PURPOSE: Radiation of the draining lymph node basin remains controversial for Merkel cell carcinoma, particularly in the era of sentinel lymph node biopsy (SLNB). METHODS AND MATERIALS: Based on a 20-year experience using SLNB-guided adjuvant radiation therapy (RT), we conducted a retrospective review of clinically node-negative patients testing 2 hypotheses: (1) whether nodal RT could be safely omitted in SLNB-negative Merkel cell carcinoma and (2) whether the excised primary site should always be radiated. Clinically node-positive patients were excluded. RESULTS: Among 57 clinically node-negative patients who underwent SLNB and wide local excision (WLE), 42 (74%) had a negative SLNB, and 15 (26%) had a positive SLNB. At a median follow-up of 43 months (range, 5-182), SLNB-negative patients irradiated to the primary site had improved 4-year disease-specific survival (100% vs 65%, P = .008), local recurrence-free survival (100% vs 76%, P = .009), and distant recurrence-free survival (100% vs 75%, P = .008), but not overall survival (87.5% vs 57.7%, P = .164) compared with SLNB-positive patients receiving comprehensive RT. Among SLNB-negative patients treated with WLE only, 67% (6/9) had a disease relapse, half of which were local relapses (33%). CONCLUSIONS: In this single-institution retrospective review, after negative SLNB and WLE, RT given only to the primary site provided 100% disease control without a need for nodal RT. Among SLNB-negative patients who had WLE, omission of postoperative primary-site RT was associated with 67% cancer relapse, of which half was local.

Development of a neonate X-ray phantom for 2D imaging applications using single-tone inkjet printing.

PURPOSE: Inkjet printers can be used to fabricate anthropomorphic phantoms by the use of iodine-doped ink. However, challenges persist in implementing this technique. The calibration from grayscale to ink density is complex and time-consuming. The purpose of this work is to develop a printing methodology that requires a simpler calibration and is less dependent on printer characteristics to produce the desired range of x-ray attenuation values. METHODS: Conventional grayscale printing was substituted by single-tone printing; that is, the superposition of pure black layers of iodinated ink. Printing was performed with a consumer-grade inkjet printer using ink made of potassium-iodide (KI) dissolved in water at 1 g/ml. A calibration for the attenuation of ink was measured using a commercial x-ray system at 70 kVp. A neonate radiograph obtained at 70 kVp served as an anatomical model. The attenuation map of the neonate radiograph was processed into a series of single-tone images. Single-tone images were printed, stacked, and imaged at 70 kVp. The phantom was evaluated by comparing attenuation values between the printed phantom and the original radiograph; attenuation maps were compared using the structural similarity index measure (SSIM), while attenuation histograms were compared using the Kullback-Leibler (KL) divergence. A region of interest (ROI)-based analysis was also performed, where the attenuation distribution within given ROIs was compared between phantom and patient. The phantom sharpness was evaluated in terms of modulation transfer function (MTF) estimates and signal spread profiles of high spatial resolution features in the image. RESULTS: The printed phantom required 36 pages. The printing queue was automated and it took about 2 h to print the phantom. The radiograph of the printed phantom demonstrated a close resemblance to the original neonate radiograph. The SSIM of the phantom with respect to that of the patient was 0.53. Both patient and phantom attenuation histograms followed similar distributions, and the KL divergence between such histograms was 0.20. The ROI-based analysis showed that the largest deviations from patient attenuation values were observed at the higher and lower ends of the attenuation range. The limiting resolution of the proposed methodology was about 1 mm. CONCLUSION: A methodology to generate a neonate phantom for 2D imaging applications, using single-tone printing, was developed. This method only requires a single-value calibration and required less than 2 h to print a complete phantom.