Hoof wall masses removal in 30 standing sedated horses: Surgical technique, postoperative complications and long-term outcome.

OBJECTIVE: To describe the surgical technique for removal of hoof wall masses in horses under standing sedation (SS) and local anesthesia (LA), and to report complications and long-term outcome following surgery. STUDY DESIGN: Observational retrospective study. ANIMALS: Client-owned horses (n = 30). METHODS: Horses undergoing keratoma removal under SS and LA in a single equine hospital between August 2016 and July 2023 were included in the study. Signalment, affected foot, history of lameness and/or foot abscesses, degree of lameness on admission, imaging findings (radiography and magnetic resonance imaging [MRI] when available), location of the mass, surgical technique, remedial farriery, postoperative care, complications and outcome were recorded. Long-term follow-up information was obtained by telephone questionnaire. RESULTS: A total of 30 horses met the inclusion criteria. Duration of lameness ranged from 1 to 289 days (mean 90 days). The degree of lameness varied from absent to grade 4/5 (AAEP) (mean grade 3/5). All horses underwent preoperative radiographic examination and 14/30 underwent MRI. All horses underwent partial hoof wall resection. The surgery was performed safely in all cases. Postoperative complications included marked lameness in the early postoperative period in 3/30 horses and exuberant granulation tissue formation in 2/30 horses. Long-term (>6 months) follow-up information was available for 28 horses, and 26/28 horses returned to previous levels of exercise. Recurrence was suspected in 1/30 horses. CONCLUSIONS: The complication rate was lower than previously reported for keratoma removal under general anesthesia (GA). CLINICAL SIGNIFICANCE: Removal of hoof wall masses under SS and LA can be considered as an alternative to removal under GA.

Use of N-acetylcysteine plus simethicone to improve mucosal visibility in upper digestive endoscopy via systematic alphanumeric-coded endoscopy: a randomized, double-blind controlled trial.

Background: The use of antifoaming and mucolytic agents prior to upper gastrointestinal (GI) endoscopy and a thorough systematic review are essential to optimize lesion detection. This study evaluated the effect of simethicone and N-acetylcysteine on the adequate mucosal visibility (AMV) of the upper GI tract by an innovative systematic method. Methods: This randomized, double-blind controlled trial included consecutive patients who underwent diagnostic upper GI endoscopy for screening for early neoplasms between August 2019 and December 2019. The upper GI tract was systematically assessed by systematic alphanumeric-coded endoscopy. Patients were divided into 4 groups: 1) water; 2) only simethicone; 3) N-acetylcysteine + simethicone; and 4) only N-acetylcysteine. The following parameters were assessed in each group: age, sex, body mass index, level of adequate mucosal visibility, and side-effects. Results: A total of 4564 images from upper GI areas were obtained for evaluation. The mean AMV in the 4 groups was 93.98±7.36%. The N-acetylcysteine + simethicone group had a higher cleaning percentage compared with the other groups (P=0.001). There was no significant difference among the remaining groups, but several areas had better cleaning when a mucolytic or antifoam alone was used. No side-effects were found in any group. Conclusion: The combination of N-acetylcysteine plus simethicone optimizes the visibility of the mucosa of the upper GI tract, which could potentially increase diagnostic yield.

Neurologic Quality of Life Outcomes in Patients with Normal Pressure Hydrocephalus After Ventriculoperitoneal Shunt Placement: A Prospective Assessment of Cognition, Mobility, and Social Participation.

BACKGROUND: Idiopathic normal pressure hydrocephalus (iNPH) typically presents with gait disturbances, cognitive decline, and urinary incontinence. Symptomatic improvement generally occurs following shunt placement, but limited evidence exists on the quality of life (QOL) metrics in iNPH. Therefore, we conducted a prospective study of the effect of shunt placement on QOL in iNPH patients, using Quality of Life in Neurologic Disorders (Neuro-QOL) metrics. METHODS: Eligible patients underwent shunt placement after evidence of symptomatic improvement following temporary CSF diversion via inpatient lumbar drain trial. Patients were administered short- and long-form Neuro-QOL assessments prior to shunt placement and at six-month and one-year postoperative timepoints to evaluate lower extremity mobility, cognitive function, and social roles and activities participation. Changes in QOL measures were analyzed using a repeated measures linear mixed effects model. RESULTS: There were forty-eight patients with a mean age of 75.4 ± 6.3 years. Average short-form mobility scores improved by 3.9 points (14.6%) at six-month follow-up and by 6.2 points (23.2%) at one-year follow-up compared to preoperative baseline (p = 0.027 and p = 0.0002, respectively). Short-form cognition scores increased by 5.2 points (22.4%) at six months and 10.9 points (47.0%) at one year postoperatively (p = 0.007 and p < 0.0001, respectively). On long-form assessment, social roles and activity participation scores improved by 29.3 points (23.4%) at six months and 31.6 points (25.2%) at one year after surgery compared to baseline (p = 0.028 and p = 0.02, respectively). CONCLUSION: Our findings demonstrate that shunt placement leads to improved QOL in iNPH patients across multiple domains. Significant improvements in mobility, cognition, and social roles and activity participation are realized within the first six months and are sustained on one-year follow-up.

Belgian Patients of the European Registry for Hidradenitis Suppurativa (ERHS-Be): Data, Scores, and Phenotypes since 2015.

INTRODUCTION: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease, characterized by painful and recurrent lesions in apocrine gland-bearing skin areas. It is a heterogeneous disease, which makes assessment and data collection difficult. Questionnaires with detailed items, such as the Belgian European Registry for Hidradenitis Suppurativa (ERHS-Be), are useful to study HS and its associated comorbidities. The aim of this registry was to uncover new factors associated with HS and understand HS patients' clinical profiles and efficacy of treatments. MATERIAL AND METHODS: The ERHS-Be registry is based on questionnaires, with sections for sociodemographic data, medical and HS history, clinical examination, and treatment plan. It allows identification of different clinical phenotypes and automatic calculation of severity scores. RESULTS: At present, 606 patients are included in the ERHS-Be (67% women, 33% men). The mean age at the first visit is 38.5 years. Tobacco use is present in 72.6% of patients. A family history of HS is noted in 42% of patients. Comorbidities are documented in this cohort: depression is present in 43.8% of patients, arthritis in 27.8%, obesity in 31.5%, hypertension in 10.6%, diabetes mellitus in 6.4%, and dyslipidemia in 12.4%. Moreover, 7.7% of patients suffer from IBD and 27.4% have a pilonidal sinus. History of severe acne is found in 32.1% of patients and psoriasis in 9.3%. Thirteen percent of women in our cohort suffer from polycystic ovarian syndrome. Severity of disease is quantified in 533 patients: for instance, Hurley I, II, and III scores proportions are, respectively, 32.3%, 52.7%, and 15%, while the mean IHS4 score is 5.2. This registry also enables determination of relative phenotype proportions in our cohort, according to different classifications. CONCLUSION: The ERHS-Be questionnaires allow systematic and larger data collection, including detailed comorbidities, phenotypes, and severity of disease. Analysis of this large database will contribute to a better understanding and management of HS, at a time where new therapeutic options are becoming available.

Identifying the best cutoff value of the fecal occult blood immunochemical test in the detection of advanced and neoplastic colorectal lesions.

Objective: Screening is an effective tool for detecting colorectal lesions in asymptomatic subjects. There is a positive correlation between fecal immunochemical test (FIT) values and the size of tumors. Despite the efficacy of screening, the detection of colorectal cancer (CRC) remains low. The primary objective was to evaluate the best FIT cutoff value for detecting advanced adenomas and CRC among individuals at average risk in a country with a high incidence and morbidity from CRC. Methods: This observational and prospective study analyzed consecutive cases in 1461 asymptomatic subjects with a positive FIT (≥ 100 ng hemoglobin [Hb]/mL) referred for colonoscopy (2012-2015) at a tertiary center in Uruguay. Results: Colorectal lesions were detected in 35.3% (516/1461) of cases, with a mean age of 62.8 ± 8.3 years. About 53.2% were men and 65.1% of the tumors were located in the left side of the colon. The size of the lesion and FIT values (p = 0.001) were positively correlated. Laterally spreading tumors predominated in the right colon (586 ng Hb/mL; 95% Confidence interval [CI] 443.4-760). One hundred and thirty-five (26%) lesions were advanced adenomas (15 ± 6.7 mm); 694.6 ng/mL; 95% CI 632.4-756.9). The highest diagnostic yield (0.5112) for advanced adenomas was at a FIT level of 400 ng Hb/mL (accuracy 88.6%). There were significant differences in FIT values early and advanced CRC (927 ng/mL; [95% CI: 637-1082] vs. 1453 [95% CI: 1352-1594; p = 0.001]). Conclusion: A FIT value of 400 ng Hb/mL was the best diagnostic yield to detect advanced adenomas and CRC. This value is useful during the COVID-19 pandemic as it allows prioritization of colonoscopy to those most at risk of significant disease, thus reducing risks to both patients and healthcare workers.

Objetivo: El cribado es una herramienta eficaz para detectar lesiones colorrectales en sujetos asintomáticos. Existe una correlación positiva entre los valores de la prueba inmunoquímica fecal (FIT) y el tamaño de los tumores. A pesar de la eficacia del cribado, la detección del cáncer colorrectal (CCR) sigue siendo baja. El objetivo principal fue evaluar el mejor valor de corte FIT para detectar adenomas avanzados y CCR entre personas con riesgo promedio en un país con alta incidencia y morbilidad por CCR. Métodos: Este estudio observacional y prospectivo analizó 1461 sujetos asintomáticos con FIT positivo (≥ 100 ng de hemoglobina [Hb]/mL) remitidos para colonoscopia (2012-2015) en un centro terciario en Uruguay. Resultados: Se detectaron lesiones colorrectales en el 35,3% (516/1461) de los casos, con una edad media de 62,8 ± 8,3 años. Alrededor del 53,2% eran hombres y el 65,1% de los tumores estaban ubicados en el lado izquierdo del colon. El tamaño de la lesión y los valores FIT (p = 0,001) se correlacionaron positivamente. Los tumores con extensión lateral predominaron en el colon derecho (586 ng Hb/mL; intervalo de confianza [IC] del 95%: 443,4-760). Ciento treinta y cinco (26%) lesiones fueron adenomas avanzados (15 ± 6,7 mm); 694,6 ng/ml; IC 95% 632,4-756,9). El rendimiento diagnóstico más alto (0,5112) para los adenomas avanzados se obtuvo con un nivel FIT de 400 ng Hb/ml (precisión del 88,6%). Hubo diferencias significativas en los valores de FIT de CCR temprano y avanzado (927 ng/mL; [IC 95%: 637-1082] vs. 1453 [IC 95%: 1352-1594; p = 0,001]). Conclusión: Un valor FIT de 400 ng Hb/mL fue el mejor rendimiento diagnóstico para detectar adenomas avanzados y CCR. Este valor es útil durante la pandemia de COVID-19, ya que permite priorizar la colonoscopia a aquellos con mayor riesgo de padecer una enfermedad importante, reduciendo así los riesgos tanto para los pacientes como para los trabajadores de la salud.

Chemical and Antiplasmodial Investigations on Eremophila-Derived Alkaloids and Semisynthetic Ether Analogues.

Microthecaline A (1), the known antiplasmodial quinoline serrulatane alkaloid from the roots of Eremophila microtheca F. Muell. ex Benth. (Scrophulariaceae), was targeted for isolation and subsequent use in the generation of a semisynthetic ether library. A large-scale extraction and isolation yielded the previously undescribed quinoline serrulatane microthecaline B (2), along with crystalline 1 that enabled the first X-ray crystallographic analysis to be undertaken on this rare alkaloid structure class. The X-ray diffraction analysis of 1 supported the absolute configuration assignment of microthecaline A, which was originally assigned by ECD data analysis. Microthecaline A (1) was converted into 10 new semisynthetic ether derivatives (3-12) using a diverse series of commercially available alkyl halides. Chemical structures of the new serrulatane alkaloid and semisynthetic ether analogues were assigned by spectroscopic and spectrometric analyses. Antiplasmodial evaluations of 1-12 showed that the semisynthetic derivative 5 elicited the most potent activity with an IC50 value of 7.2 µM against Plasmodium falciparum 3D7 (drug-sensitive) strain.

Semisynthesis and Cytotoxic Evaluation of an Ether Analogue Library Based on a Polyhalogenated Diphenyl Ether Scaffold Isolated from a Lamellodysidea Sponge.

The known oxygenated polyhalogenated diphenyl ether, 2-(2',4'-dibromophenoxy)-3,5-dibromophenol (1), with previously reported activity in multiple cytotoxicity assays was isolated from the sponge Lamellodysidea sp. and proved to be an amenable scaffold for semisynthetic library generation. The phenol group of 1 was targeted to generate 12 ether analogues in low-to-excellent yields, and the new library was fully characterized by NMR, UV, and MS analyses. The chemical structures for 2, 8, and 9 were additionally determined via single-crystal X-ray diffraction analysis. All natural and semisynthetic compounds were evaluated for their ability to inhibit the growth of DU145, LNCaP, MCF-7, and MDA-MB-231 cancer cell lines. Compound 3 was shown to have near-equivalent activity compared to scaffold 1 in two in vitro assays, and the activity of the compounds with an additional benzyl ring appeared to be reliant on the presence and position of additional halogens.

Up against the wall - emergency double myocardial rupture repair.

BACKGROUND: Left ventricular free wall rupture (LVFWR) and interventricular septal rupture (VSR) are potentially catastrophic mechanical complications after acute myocardial infarction (AMI). When they occur together, "double myocardial rupture" (DMR), survival is unlikely. DMR is seen in only 0.3% of all AMIs. With or without surgical intervention, the odds are against the patient. CASE PRESENTATION: A 57-year-old male self-referred to the emergency department of a remote hospital 5 days after first experiencing chest pain. Investigations in ED confirmed an inferior ST-segment elevation myocardial infarction (STEMI) complicated by DMR. Coronary angiography revealed a mid-course total occlusion of the right coronary artery (RCA). He was rapidly transferred to our regional cardiac surgical unit, arriving straight into the operating theatre, in cardiogenic shock. He was briefly conscious, before arresting prior to intubation and being massaged onto bypass. Not only did he survive the all-night operation, requiring a mitral valve replacement in the process, but he survived multiple postoperative complications to be eventually transferred on postoperative day 66, neurologically intact, to a peripheral unit to complete his rehabilitation. He was subsequently discharged home 88 days after the operation and was able to ambulate with a walking frame into his first postoperative follow-up clinic appointment. CONCLUSIONS: Our patient, against all odds, has survived DMR and multiple postoperative complications. We present the details of his case and the literature surrounding the condition. The patient's mental fortitude and his supportive family played a significant role, along with excellent multidisciplinary team work, in assuring his survival.

Western outcomes of circumferential endoscopic submucosal dissection for early esophageal squamous cell carcinoma.

BACKGROUND AND AIMS: Circumferential endoscopic submucosal dissection (cESD) in the esophagus has been reported to be feasible in small Eastern case series. We assessed the outcomes of cESD in the treatment of early esophageal squamous cell carcinoma (ESCC) in Western countries. METHODS: We conducted an international study at 25 referral centers in Europe and Australia using prospective databases. We included all patients with ESCC treated with cESD before November 2022. Our main outcomes were curative resection according to European guidelines and adverse events. RESULTS: A total of 171 cESDs were performed on 165 patients. En bloc and R0 resections rates were 98.2% (95% confidence interval [CI], 95.0-99.4) and 69.6% (95% CI, 62.3-76.0), respectively. Curative resection was achieved in 49.1% (95% CI, 41.7-56.6) of the lesions. The most common reason for noncurative resection was deep submucosal invasion (21.6%). The risk of stricture requiring 6 or more dilations or additional techniques (incisional therapy/stent) was high (71%), despite the use of prophylactic measures in 93% of the procedures. The rates of intraprocedural perforation, delayed bleeding, and adverse cardiorespiratory events were 4.1%, 0.6%, and 4.7%, respectively. Two patients died (1.2%) of a cESD-related adverse event. Overall and disease-free survival rates at 2 years were 91% and 79%. CONCLUSIONS: In Western referral centers, cESD for ESCC is curative in approximately half of the lesions. It can be considered a feasible treatment in selected patients. Our results suggest the need to improve patient selection and to develop more effective therapies to prevent esophageal strictures.

Solvent-Directed Construction of a Nanoporous Metal-Organic Framework with Potential in Selective Adsorption and Separation of Gas Mixtures Studied by Grand Canonical Monte Carlo Simulations.

In this report, a microporous metal-organic framework of [Ca(TDC)(DMA)]n (1) and a two-dimensional coordination polymer of [Ca(TDC)(DMF)2 ]n (2), (TDC2- =Thiophene-2,5-dicarboxylate, DMA=N, N'-dimethylacetamide and DMF=N, N'-dimethylformamide) based on Ca(II) were designed by the effect of solvent, and X-ray analysis was performed for the single crystals of 1 and 2. Then, compound 1 was synthesized in three different methods and identified with a set of analyses. Compared to other adsorbents, MOFs are widely used in the field of adsorption and separation of various gases due to a series of distinctive features such as diverse and adjustable structures pores with different dimensions, high porosity and surface area with regular distribution of active sites. Therefore, the ability of 1 to uptake single gases (CH4 , CO2 , C2 H2 , H2, and N2 ) and separation of several binary mixtures of gases (CO2 /CH4 , CO2 /N2 , CO2 /H2 and CO2 /C2 H2 ), were investigated using Grand Canonical Monte Carlo simulations. Volumetric and gravimetric adsorption isotherms in various operating conditions, the isosteric heat of adsorption (qst ), the chemical potential for each thermodynamic state, and snapshots during the simulation process were reported in all cases. The results obtained from the adsorption simulation indicate that compound 1 has a high capacity for uptake of H2 (16 mmol g-1 ) and N2 (12.5 mmol g-1 ), CO2 (6.6 mmol g-1 ), C2 H2 (5 mmol g-1 ) and CH4 (1.5 mmol g-1 ) gases at 1 bar. It also performs well in separating CO2 in binary mixtures, which can be attributed to the presence of open metal sites in nodes of 1 and their electrostatic tendency to interact with CO2 containing the higher quadrupole dipole moment compared to other components of the mixture.

High incidence of antibiotic resistance amongst isolates of Helicobacter pylori collected in Nottingham, UK, between 2001 and 2018.

Introduction. Helicobacter pylori is the leading cause of peptic ulcers and gastric cancer. The most common treatment regimens use combinations of two or three antibiotics and a proton pump inhibitor (PPI) to suppress stomach acid. The World Health Organization designated clarithromycin-resistant H. pylori as a high priority pathogen for drug development, due to increasing antibiotic resistance globally.Hypothesis/Gap Statement. There is no routine surveillance of H. pylori primary antimicrobial sensitivities in the UK, and published data are lacking.Aim. This study aimed to characterize antimicrobial sensitivities of isolates collected in Nottingham, UK, between 2001 and 2018.Methodology. Gastric biopsy samples were collected, with informed written consent and ethics approval, from 162 patients attending the Queen's Medical Centre in Nottingham for an upper GI tract endoscopy. Antibiotic sensitivity was assessed using E-Tests and a more cost-effective disc diffusion test.Results. The clarithromycin, amoxicillin and levofloxacin disc diffusion tests provided identical results to E-Tests on a subset of 30 isolates. Disparities were observed in the metronidazole test results, however. In total, 241 isolates from 162 patients were tested using at least one method. Of all isolates, 28 % were resistant to clarithromycin, 62 % to metronidazole and 3 % to amoxicillin, which are used in first-line therapies. For those antibiotics used in second- and third-line therapies, 4 % were resistant to levofloxacin and none of the isolates were resistant to tetracycline. Resistance to more than one antibiotic was found in 27 % of isolates. The frequency of patients with a clarithromycin-resistant strain increased dramatically over time: from 16 % between 2001 and 2005 to 40 % between 2011 and 2018 (P=0.011). For the same time periods, there was also an increase in those with a metronidazole-resistant strain (from 58 to 78 %; P=0.05). The frequencies of clarithromycin and metronidazole resistance were higher in isolates from patients who had previously received eradication therapy, compared to those who had not (40 % versus 77 %, and 80 % versus 92 %, respectively). Of 79 pairs of isolates from the antrum and corpus regions of the same patient's stomach, only six had differences in their antimicrobial susceptibility profiles.Conclusion. Although there was high and increasing resistance to clarithromycin and metronidazole, there was no resistance to tetracycline and the frequencies of amoxicillin and levofloxacin resistance were very low.

Does the Type of Surgical Headwear Worn in the OR Matter? A Review of Evidence and Opinions.

Proper surgical attire is essential in decreasing surgical site infections; however, the effectiveness of the different types of headwear is a controversial topic. We conducted a narrative review based on studies identified through a focused literature search to summarize and critically assess evidence and opinions on the most appropriate type of headwear for OR personnel. We included 48 articles: 17 original research studies and 31 non-peer-reviewed articles of various types. Research published before 2014 mostly supports the complete coverage of all hair, which aligns with the 2015 AORN guidelines. However, more recent literature rebuts these guidelines and emphasizes the importance of clean headwear. Although earlier studies (published before 2017) lacked scientific rigor, later studies (published after 2017) have other various limitations, including missing data on compliance, surgery-related techniques, and surgical attire other than headwear. The findings from this review highlight the importance of solid evidence-based guidelines and expert collaboration.

A cis-ß-iron(III) SALPN catalyst for hydrogen atom transfer reductions and olefin cross couplings.

An inexpensive Fe(III) SALPN catalyst for MHAT reactions such as reductions of α,ß-unsaturated carbonyl compounds and olefin cross couplings is reported. The majority of these reactions proceeded in good yields and high stereoselectivities with low catalyst loadings at room temperature.

Subinternship in Diagnostic Radiology: Bringing the Shadowers Out of the Shadows.

RATIONALE AND OBJECTIVES: Diagnostic radiology subinternships are uncommon. We started a diagnostic radiology subinternship at our institution in 2020 and present 3 years of data assessing the impact of the course on students' perceptions of and interest in diagnostic radiology. MATERIALS AND METHODS: The initial course design consisted of daily shadowing shifts, small group lectures with attending radiologists, asynchronous self-paced learning assignments, an ultrasound skills session, multidisciplinary tumor board attendance, and completion of 2 formal case presentations. "Junior resident" shifts, where students dictated studies under attending supervision, an emergency radiology call shift, and an ultrasound procedures shift were subsequently added in response to student feedback. Students were asked to complete surveys before and after completing the course. RESULTS: Forty-seven fourth-year medical students completed the course over 3 years. The first 2 groups were predominantly male, whereas the third group showed near even gender representation (54% male). 21 (45%) chose to apply to diagnostic radiology for residency. Student reported interest in diagnostic radiology as a career, valuation of diagnostic radiology as a specialty, comfort with imaging interpretation, and perceptions of the availability of patient interaction and procedures in diagnostic radiology all significantly increased after participation in the course. Students ranked the junior resident shifts and small group attending lectures as the most valuable course components. CONCLUSION: Implementation of a diagnostic radiology subinternship significantly improved students' interest in and perceptions of the field. We encourage the creation of similar courses in other radiology departments and stress the importance of active learning experiences.

Bromodomain and extraterminal protein-targeted probe enables tumour visualisation in vivo using positron emission tomography.

Bromodomain and extraterminal (BET) proteins, a family of epigenetic regulators, have emerged as important oncology drug targets. BET proteins have not been targeted for molecular imaging of cancer. Here, we report the development of a novel molecule radiolabelled with positron emitting fluorine-18, [18F]BiPET-2, and its in vitro and preclinical evaluation in glioblastoma models.

Pre-targeting amyloid-ß with antibodies for potential molecular imaging of Alzheimer's disease.

With the aim of developing the concept of pretargeted click chemistry for the diagnosis of Alzheimer's disease two antibodies specific for amyloid-ß were modified to incorporate trans-cyclooctene functional groups. Two bis(thiosemicarbazone) compounds with pendant 1,2,4,5-tetrazine functional groups were prepared and radiolabelled with positron emitting copper-64. The new copper-64 complexes rapidly react with the trans-cyclooctene functionalized antibodies in a bioorthogonal click reaction and cross the blood-brain barrier in mice.

Electronic and Steric Effects on the Reactivity of Seleniranium Ions with Alkenes in the Gas Phase.

Gas phase ion-molecule reactions between seleniranium ions, R-c-SeCH2CH2+, and cis-cyclooctene were used to probe electronic and steric effects of substituents on kinetics and branching ratios. The second-order rate coefficients increased in the order p-OMeC6H4 < C6H5 < p-BrC6H4 < p-CF3C6H4 < m-NO2C6H4, giving a Hammett plot with R2 = 0.98 and ρ = +1.66. The two main pathways include direct transfer of the selenium moiety to the incoming alkene (π-ligand exchange) and the less favored ring-opening by attack at an iranium carbon to give a cis-bicyclic selenonium ion as supported by density functional theory (DFT) calculations. Branching ratios of each pathway indicated that electron-withdrawing groups directed more attack at carbon than selenium in agreement with previous solution-phase results. Increased steric bulk on selenium was investigated by changing the R group from a methyl to t-butyl, which not only shut down π-ligand exchange but also significantly reduced the overall reactivity. Finally, the reactivity of the iranium ion derived from Se-methylselenocysteine was investigated and shown to react faster and favor π-ligand exchange as the leaving group was changed from ethene to acrylic acid.

The effect of procedural time on dysplasia detection rate during endoscopic surveillance of Barrett's esophagus.

BACKGROUND : Endoscopic surveillance of Barrett's esophagus (BE) with Seattle protocol biopsies is time-consuming and inadequately performed in routine practice. There is no recommended procedural time for BE surveillance. We investigated the duration of surveillance procedures with adequate tissue sampling and effect on dysplasia detection rate (DDR). METHODS : We performed post hoc analysis from the standard arm of a crossover randomized controlled trial recruiting patients with BE (≥C2 and/or ≥M3) and no clearly visible dysplastic lesions. After inspection with white-light imaging, targeted biopsies of subtle lesions and Seattle protocol biopsies were performed. Procedure duration and biopsy number were stratified by BE length. The effect of endoscopy-related variables on DDR was assessed by multivariable logistic regression. RESULTS : Of 142 patients recruited, 15 (10.6 %) had high grade dysplasia/intramucosal cancer and 15 (10.6 %) had low grade dysplasia. The median procedural time was 16.5 minutes (interquartile range 14.0-19.0). Endoscopy duration increased by 0.9 minutes for each additional 1 cm of BE length. Seattle protocol biopsies had higher sensitivity for dysplasia than targeted biopsies (86.7 % vs. 60.0 %; P = 0.045). Longer procedural time was associated with increased likelihood of dysplasia detection on quadrantic biopsies (odds ratio [OR] 1.10, 95 %CI 1.00-1.20, P = 0.04), and for patients with BE > 6 cm also on targeted biopsies (OR 1.21, 95 %CI 1.04-1.40; P = 0.01). CONCLUSIONS : In BE patients with no clearly visible dysplastic lesions, longer procedural time was associated with increased likelihood of dysplasia detection. Adequate time slots are required to perform good-quality surveillance and maximize dysplasia detection.

An approach to assessing the contribution of the high LET effect in strategies for Auger endoradiotherapy.

Purpose: The interest in exploiting Auger emitters in cancer therapy stems from their high linear energy transfer (LET)-type radiation damage to DNA. However, the design of Auger-emitter labeled vehicles that target the Auger cascade specifically to the DNA of tumour cells is challenging. Here we suggest a possible approach to evaluate tumour-targeting Auger-labeled conjugates by assessing the impact of a radioprotector known to be effective in protecting from low LET radiation, but not high LET radiation. Given some similarity between the energy spectrum of Auger electrons and that of secondary electrons from soft X-rays, we report the results of radioprotection experiments with 25 kVp X-rays. Materials and methods: Clonogenic survival curves for cultured human keratinocytes were established for three different irradiation conditions: 137Cs γ-rays, 25 kVp X-rays and 320 kVp X-rays, and the effect of including a new radioprotector, denoted "2PH", was investigated.Results: The extent of radioprotection by 2PH was comparable for all radiation conditions, although RBE was higher (about 1.7) for soft X-rays. Conclusions: Radioprotectors like 2PH will help to evaluate Auger endoradiotherapy strategies, by determining the relative contributions of the high-LET effects (not protected), compared to other components, such as Auger electrons not effectively targeted to DNA.