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Study of the Mechanism of 7‐<i>exo</i>‐<i>trig</i> Cyclizations of Aryl, Vinyl, and Alkyl Radicals on Oxime Ethers

AbstractIn this work, we conducted a study of 7‐exo‐trig cyclizations mechanism involving aryl, vinyl, and alkyl radicals on oxime ethers. Initially, the reaction of brominated oxime ether 9 a with (TMS)3SiH and AIBN gave rise to aryl radicals that underwent a 7‐exo‐trig cyclization on the oxime ether, yielding dibenzoxepine 10 a, and the ipso reaction and reduction products were obtained as well. Approximate rate constants at 80 °C for the 7‐exo‐trig (1.0×108 s−1) and the ipso cyclization (4.3×107 s−1) were determined by competition experiments. DFT calculations showed good agreement with the experimental results. The reduction rate constant of the N‐alkoxyaminyl radical with (TMS)3SiH was calculated to be 4.1×10−1 M−1 s−1; while the rate constants for the 7‐exo‐trig cyclizations of vinyl and alkyl radicals on the oxime ether were estimated in the ranges of 106 s−1–108 s−1 and 103 s−1–108 s−1, respectively. The 7‐exo‐trig cyclization reactions involving aryl, vinyl, and alkyl radicals with oxime ethers were found to be an exothermic and irreversible process, with the oximic carbon showing a preference for nucleophilic alkyl radicals. This kinetic study contributes to the deeper understanding of radical‐mediated cyclizations, enabling the efficient design of complex synthetic routes.

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Cut-off points of neck and waist circumference as predictors of obstructive sleep apnea in the Colombian population: a comparison with polysomnography.

Neck circumference (NC) is a useful anthropometric measure for predicting obstructive sleep apnea (OSA). Ethnicity and sex also influence obesity phenotypes. NC cut-offs for defining OSA have not been established for the Latin American population. To evaluate NC, waist circumference (WC), and body mass index (BMI) as predictors of OSA in the Colombian population and to determine optimal cut-off points. Diagnostic tests were conducted at the Javeriana University, Bogota. Adults from three cities in Colombia were included. NC, WC, and BMI were measured, and a polysomnogram provided the reference standard. The discrimination capacity and best cut-off points for diagnosing OSA were calculated. 964 patients were included (57.7% men; median age, 58 years) and 43.4% had OSA. The discrimination capacity of NC was similar for men and women (area under curve, AUC 0.63 versus 0.66, P=0.39) but better for women under 60 years old (AUC 0.69 versus 0.57, P<0.05). WC had better discrimination capacity for women (AUC 0.69 versus 0.57, P<0.001). There were no significant differences in BMI. Optimal NC cut-off points were 36.5cm for women (sensitivity [S]: 71.7%, specificity [E]: 55.3%) and 41 cm for men (S: 56%, E: 62%); and for WC, 97 cm for women (S: 65%, E: 69%) and 99 cm for men (S: 53%, E: 58%). NC and WC have moderate discrimination capacities for diagnosing OSA. The cut-off values suggest differences between Latin- and North American as well as Asian populations.

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Are the Chicago 3.0 manometric diagnostics consistent with Chicago 4.0?

There is little information on the degree of concordance between the results obtained using the Chicago 3.0 (CCv3.0) and Chicago 4.0 (CCv4.0) protocols to interpret high-resolution manometry (HRM) seeking to determine the value provided by the new swallowing maneuvers included in the last protocol. This is a study of diagnostic tests, evaluating concordance by consistency between the results obtained by the CCv3.0 and CCv4.0 protocols, in patients undergoing HRM. Concordance was assessed with the kappa test. Bland-Altman scatter plots, and Lin's correlation-concordance coefficient (CCC) were used to assess the agreement between IRP measured with swallows in the supine and seated position or with solid swallows. One hundred thirty-two patients were included (65% women, age 53 ± 17years). The most frequent HRM indication was dysphagia (46.1%). Type I was the most common type of gastroesophageal junction. The most frequent CCv4.0 diagnoses were normal esophageal motility (68.9%), achalasia (15.5%), and ineffective esophageal motility (IEM; 5.3%). The agreement between the results was substantial (Kappa 0.77 ± 0.05), with a total agreement of 87.9%. Diagnostic reclassification occurred in 12.1%, from IEM in CCv3.0 to normal esophageal motility in CCv4.0. Similarly, there was a high level of agreement between the IRP measured in the supine compared to the seated position (CCC0.92) and with solid swallows (CCC0.96). In conclusion, the CCv4.0 protocol presents a high concordance compared to CCv3.0. In the majority of manometric diagnoses there is no reclassification of patients with provocation tests. However, the more restrictive criteria of CCv4.0 achieve a better reclassification of patients with IEM.

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Meckel's diverticulum: analysis of 27 cases in an adult population.

Meckel's diverticulum is a rare congenital pathology among newborns. Nevertheless, it is an uncommon abdominal pathology in the adult population. Therefore, we aim to provide a detailed account of our surgical approach in treating 27 cases of Meckel's diverticulum. This study is a cross-sectional analysis that utilized a database with prospectively collected data from 2004 to 2022. All patients under the age of 18 were excluded from the population. We described the population's demographic characteristics, symptoms, anatomopathological study, surgical technique, complications, morbidity, and mortality. A subgroup analysis was performed between the symptomatic and asymptomatic patients. A total of 27 patients who underwent surgical resection for a posteriorly diagnosed Meckel's diverticulum were included. The male population accounted for 81.4% (n = 22) of the sample size. The symptomatic group consisted of 18 male and four female patients. Abdominal pain was the predominant symptom in 85% of the patients. Out of the 22 symptomatic patients, only 9% had a positive perioperative diagnosis of Meckel's diverticulum. All 27 patients with diverticulum diagnosis received the resection through diverticulectomy (n = 6), small bowel resection with end-to-end anastomosis (n = 6), and small bowel resection with lateral to lateral anastomosis (n = 15). The mean distance between the diverticulum and the ileocecal valve was 63.4 cm. The symptomatic group had an average diverticulum length of 3.54 cm, with an average base width of 2.47 cm. In the other group, the values were 2.75 and 1.61 cm. The average length of hospital stay in the symptomatic group was 7.3 days. Meckel's diverticulum is a rare pathology in the adult population. Its presentation varies from asymptomatic to symptomatic patients, and surgery is the cornerstone treatment for this pathology.

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Descriptive Epidemiology of Melanoma Diagnosed between 2010 and 2014 in a Colombian Cancer Registry and a Call for Improving Available Data on Melanoma in Latin America.

We aimed to improve the available information on morphology and stage for cutaneous melanoma in the population-based cancer registry of the Bucaramanga Metropolitan Area in Colombia. The incidence and survival rates and the distribution of melanoma patients by age, gender, anatomical subsite, and histological subtype were calculated. All 113 melanoma patients (median age 61) were followed up (median time 7.4 years). This exercise (filling in missing information in the registry by manual search of patient clinical record and other available information) yielded more identified invasive melanomas and cases with complete information on anatomical localization and stage. Age-standardized incidence and mortality rates were 1.86 and 1.08, being slightly higher for males. Most melanomas were localized on the lower limbs, followed by the trunk. For 35% of all melanomas, the morphological subtype remained unknown. Most of the remaining melanomas were nodular and acral lentiginous melanomas. Overall global and relative 5-year survival was 61.6% and 71.3%, respectively, with poorer survival for males than females. Melanomas on the head and neck and unspecified anatomical sites had the worst survival. Patients without stage information in their medical files had excellent survival, unlike patients for whom medical files were no longer available. This study shows the possibility of improving data availability and the importance of good quality population-based data.

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Effect of Petiveria alliacea Extracts on Metabolism of K562 Myeloid Leukemia Cells.

Previously, studies have shown that leukemic cells exhibit elevated glycolytic metabolism and oxidative phosphorylation in comparison to hematopoietic stem cells. These metabolic processes play a crucial role in the growth and survival of leukemic cells. Due to the metabolic plasticity of tumor cells, the use of natural products has been proposed as a therapeutic alternative due to their ability to attack several targets in tumor cells, including those that could modulate metabolism. In this study, the potential of Petiveria alliacea to modulate the metabolism of K562 cell lysates was evaluated by non-targeted metabolomics. Initially, in vitro findings showed that P. alliacea reduces K562 cell proliferation; subsequently, alterations were observed in the endometabolome of cell lysates treated with the extract, mainly in glycolytic, phosphorylative, lipid, and amino acid metabolism. Finally, in vitro assays were performed, confirming that P. Alliacea extract decreased the oxygen consumption rate and intracellular ATP. These results suggest that the anti-tumor activity of the aqueous extract on the K562 cell line is attributed to the decrease in metabolites related to cell proliferation and/or growth, such as nucleotides and nucleosides, leading to cell cycle arrest. Our results provide a preliminary part of the mechanism for the anti-tumor and antiproliferative effects of P. alliacea on cancer.

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Ecotoxicology Evaluation of a Fenton-Type Process Catalyzed with Lamellar Structures Impregnated with Fe or Cu for the Removal of Amoxicillin and Glyphosate.

Antibiotics and pesticides, as well as various emerging contaminants that are present in surface waters, raise significant environmental concerns. Advanced oxidation processes, which are employed to eliminate these substances, have demonstrated remarkable effectiveness. However, during the degradation process, by-products that are not completely mineralized are generated, posing a substantial risk to aquatic ecosystem organisms; therefore, it is crucial to assess effluent ecotoxicity following treatment. This study aimed to assess the toxicity of effluents produced during the removal of amoxicillin and glyphosate with a Fenton-type process using a laminar structure catalyzed with iron (Fe) and copper (Cu). The evaluation included the use of Daphnia magna, Selenastrum capricornutum, and Lactuca sativa, and mutagenicity testing was performed using strains TA98 and TA100 of Salmonella typhimurium. Both treated and untreated effluents exhibited inhibitory effects on root growth in L. sativa, even at low concentrations ranging from 1% to 10% v/v. Similarly, negative impacts on the growth of algal cells of S. capricornutum were observed at concentrations as low as 0.025% v/v, particularly in cases involving amoxicillin-copper (Cu) and glyphosate with copper (Cu) and iron (Fe). Notably, in the case of D. magna, mortality was noticeable even at concentrations of 10% v/v. Additionally, the treatment of amoxicillin with double-layer hydroxides of Fe and Cu resulted in mutagenicity (IM ≥ 2.0), highlighting the necessity to treat the effluent further from the advanced oxidation process to reduce ecological risks.

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