Enigmazole C: A Cytotoxic Macrocyclic Lactone and Its Ring-Opened Derivatives from a New Species of Homophymia Sponge.

A new macrolide, enigmazole C (1), and two additional analogues, enigmazoles E (2) and D (3), were obtained from a new species of the Homophymia genus as part of an ongoing discovery program at PharmaMar to study cytotoxic substances from marine sources. The structures were fully characterized by cumulative analyses of NMR, IR, and MS spectra, along with density functional theory computational calculations. All three of the new compounds feature an unusual 2,3-dihydro-4H-pyran-4-one moiety, but only enigmazoles C (1) and D (3) showed cytotoxic activity in the micromolar range against A-549 (lung), HT-29 (colon), MDA-MB-231 (breast), and PSN-1 (pancreas) tumor cells.

Indium(III)-Catalyzed Stereoselective Synthesis of Tricyclic Frameworks by Cascade Cycloisomerization Reactions of Aryl 1,5-Enynes.

The indium(III)-catalyzed cascade cycloisomerization reaction of 1,5-enynes with pendant aryl nucleophiles is reported. The reaction proceeds in cascade under mild reaction conditions, using InI3 (5 mol %) as a catalyst with a range of 1,5-enynes furnished with aryl groups (phenyl and phenol) at alkene (E and Z isomers) and with terminal and internal alkynes. Using 1-bromo-1,5-enynes, a one-pot sequential indium-catalyzed cycloisomerization and palladium-catalyzed cross-coupling with triorganoindium reagents were developed. The double cyclization is stereospecific and operates via a biomimetic cascade cation-olefin through 1,5-enyne cyclization (6-endo-dig) and subsequent C-C hydroarylation or C-O phenoxycyclization. Density functional theory (DFT) computational studies on 1,5-enynyl aryl ethers support a two-step mechanism where the first stereoselective 1,5-enyne cyclization produces a nonclassical carbocation intermediate that evolves to the tricyclic reaction product through a SEAr mechanism. Using this approach, a variety of tricyclic heterocycles such as benzo[b]chromenes, phenanthridines, xanthenes, and spiroheterocyclic compounds are efficiently synthesized with high atom economy.

Impact of a focused trauma course on retention of provider skills, knowledge and confidence at a regional hospital in the Dominican Republic.

INTRODUCTION: Road traffic accidents are a public health epidemic, causing significant morbidity and mortality in low- and middle-income countries. The Dominican Republic (DR) ranks among the highest road traffic fatality rates in the world. There is no formalized trauma curriculum in the DR. A short trauma course was implemented at a San Pedro de Macoris, DR hospital with pre-, post- and retention evaluation of the knowledge, skills and confidence of the providers. METHODS: A 4-day trauma course was developed for medical students and residents. On days 1 and 4, providers completed pre- and post-training assessments consisting of a 40-question written exam, 1 simulation case and a trauma confidence questionnaire. Simulation cases were evaluated using a critical actions checklist and a non-technical skills scale (TNOTECHS). Assessments were repeated in 2 months to evaluate for knowledge, skill and confidence retention. A repeated measures ANOVA model was used to evaluate pre-, post- and retention training differences in the written exam, non-technical skills and critical actions scores. Confidence scores were assessed using a cumulative logistic regression model. RESULTS: A total of 65 people participated (36 medical students, 22 EM and 7 family medicine residents). Of the 65 participants, 39, 22 and 21 participants had complete scores for pre-post, pre-retention and post-retention comparisons respectively. Mean test scores for the written exam were 37.2, 63.5 and 52.2 for pre, post and retention results respectively. Comparisons between pre and post as well as pre and retention showed statistically significant differences (p=0.0001). Mean TNOTECHS total scores were 15.8, 21.3 and 20.8 for pre-, post- and retention results respectively with a significant difference found between pre- and post- training and pre- and retention training (p <0.05). Simulation mean checklist scores were 57.7%, 67.8% and 74.1% for pre-, post- and retention training respectively with a significant difference established between pre- and retention scores (p<0.05). Provider opinion that their ED patients received best care possible and patients' needs were identified and addressed showed statistically significant increases. CONCLUSION: A short trauma course can improve trauma specific knowledge, skills and confidence with significant retention at two months. A longitudinal trauma curriculum may bolster retention.

Recognizing and managing emerging infectious diseases in the emergency department [digest].

With population shifts, increased travel, and climate change, the spread of emerging and re-emerging infections is increasing. Although encountering a patient with an emerging infection on any given emergency department shift is unlikely, missing a diagnosis could have profound consequences for the patient, healthcare workers, and the patient's close contacts. This review provides a framework to evaluate, diagnose, and treat a returning traveler with suspected Middle East respiratory syndrome, chikungunya virus, or Zika virus-3 recently emerged infections. All may present with nonspecific viral-like symptoms and are easily missed if an appropriate travel history is not obtained. A high level of vigilance and proper disposition will enable the emergency clinician to effectively diagnose, manage, and contain these diseases. [Points & Pearls is a digest of Emergency Medicine Practice.].

Recognizing and managing emerging infectious diseases in the emergency department.

With population shifts, increased travel, and climate change, the spread of emerging and re-emerging infections is increasing. Although encountering a patient with an emerging infection on any given emergency department shift is unlikely, missing a diagnosis could have profound consequences for the patient, healthcare workers, and the patient's close contacts. This review provides a framework to evaluate, diagnose, and treat a returning traveler with suspected Middle East respiratory syndrome, chikungunya virus, or Zika virus-3 recently emerged infections. All may present with nonspecific viral-like symptoms and are easily missed if an appropriate travel history is not obtained. A high level of vigilance and proper disposition will enable the emergency clinician to effectively diagnose, manage, and contain these diseases.

Synthesis of Thelepamide via Catalyst-Controlled 1,4-Addition of Cysteine Derivatives and Structure Revision of Thelepamide.

The first enantioselective total synthesis and structural reassignment of (-)-thelepamide, a cytotoxic tetraketide-amino acid from the marine worm Thelepus crispus, is reported. A convergent approach provides access to all thelepamide diastereomers in six steps from four simple building blocks. Key features of the synthesis include the application of Melchiorre's organocatalytic thia-Michael reaction and a sonication-assisted assembly of an unprecedented N,O-acetal-hemiacetal moiety. The corrected structure was confirmed by NMR-DFT analysis.

Sarcoma de Kaposi epidémico: papel de la radioterapia: experiencia del Hospital Universitario de Caracas 1984-1996 / Epidemic kaposi sarcoma: paper of the radiotherapy: experience in the Hospital Universitario de Caracas 1984-1996

El presente trabajo es un análisis retrospectivo de 75 casos de Sarcoma de Kaposi Epidémico vistos en el Hospital Universitario de Caracas en el período comprendido entre el 1º de enero de 1984 y el 30 de junio de 1996. De éstos, 26 recibieron tratamiento radiante en el Servicio de Radioterapia. Todos los pacientes fueron del sexo masculino, edad promedio de 38 años, con predominio de homosexuales (43 por ciento). La presentación más común fue en piel (77 por ciento). El contaje de linfocitos CD4 fue poco realizado (17 por ciento). El diagnóstico clínico se realizó en el 45 por ciento de los casos y sólo un 42,6 por ciento fue referido a consulta especializada. Radioterapia es el tratamiento de elección en la variedad epidémica para paliación del dolor, edema, alteraciones funcionales y cosmesis. Es un tumor radiosensible, 38 por ciento se trataron con dosis entre 2000-3000 cGys, siendo el fraccionamiento más empleado de 200 cGys/día (42 por ciento). El seguimiento ha sido inadecuado, 50 por ciento se pierde de control o fallece en el curso de primeros 6 meses. Un caso tuvo una sobrevida mayor de 7 años. Realizar estudios prospectivos con historia especializada, determinación de linfocitos CD4, examen detallado de piel y cavidad oral, confirmación histológica de lesiones sospechosas, referencia a consultas especializadas, empleo de nuevos esquemas de fraccionamiento radiante y adecuado seguimiento

Estado actual de la radioterapia en Venezuela / Actual state of the radiotherapy in Venezuela

Este trabajo se realiza como una actualización de otro anteriormente hecho por la Cátedra de Radioterapia y Medicina Nuclear de la Universidad Central de Venezuela de 1986. Con este fin se visitaron 18 centros públicos de radioterapia, obteniéndose información sobre ambiente físico, unidades de tratamiento, braquiterapia, personal médico y paramédico, registro de dator clínicos de pacientes. Resultado: solo 4 de 7 unidades de altovoltaje funcionan; existen 20 unidades de Co60, de las cuales 17 funcionan y únicamente 2 lo hacen en forma adecuada. De los 7 aceleradores lineales y 7 simuladores existentes, únicamente funcionan 5 de cada uno. Unicamente 3 centros hacen dosimetría por computación el resto lo hace en forma manual. En el 50 por ciento de los servicios de radioterapia, los equipos de braquiterapia intracavitaria se encuentran en condiciones precarias. Dos hospitales poseen equipos de braquiterapia a control remoto. Existe un déficit importante de técnicas en radioterapia, físicos en radiaciones y dosimetristas. en conclusión la radioterapia en Venezuela confronta serios problemas debido a la falta de recursos materiales y humanos. Recomendamos la sustitución de equipos con DFP menor de 80 cm., el cambio de las fuentes de Co60 con rendimientos menores de 100 cGy/min., el remplazo de las fuentes y de los equipos de radioterapia intracavitaria, la dotación de simuladores, entrenamiento de personal técnico y formación de físicos y dosimetristas