Synthesis of a [18F]F Estradiol Derivative via Click Chemistry Using an Automated Synthesis Module: In Vitro Evaluation as Potential Radiopharmaceutical for Breast Cancer Imaging.

"Click reactions" are a very useful tool for the selective conjugation of different molecular subunits to produce complex structures in a simple way. In this paper, we present the application of Cu(I)-catalyzed biorthogonal reactions between alkynes and azides to the indirect radiofluorination of an estradiol derivative with potential applications in estrogen receptor imaging. The procedure was fully developed on an automated synthesis platform, and conditions were optimized to achieve the desired product with a reasonable yield without precipitation. Although the biological results were not adequate for a potential radiopharmaceutical, the outcome of this work is valuable since the use of automated platforms is required for the reliable and reproducible preparation of PET radiopharmaceuticals in GMP conditions while limiting the radiation dose rates to the personnel.

Colonization dynamics of subgingival microbiota in recently installed dental implants compared to healthy teeth in the same individual: a 6-month prospective observational study.

OBJECTIVES: To evaluate the colonization dynamics of subgingival microbiota established over six months around newly installed dental implants in periodontally healthy individuals, compared with their corresponding teeth. METHODOLOGY: Seventeen healthy individuals assigned to receive single dental implants participated in the study. Subgingival biofilm was sampled from all implant sites and contralateral/ antagonist teeth on days 7, 30, 90, and 180 after implant installation. Microbiological analysis was performed using the Checkerboard DNA-DNA hybridization technique for detection of classical oral taxa and non-oral microorganisms. Significant differences were estimated by Mann-Whitney and Friedman tests, while associations between implants/teeth and target species levels were assessed by linear regression analysis (LRA). Significance level was set at 5%. RESULTS: Levels of some species were significantly higher in teeth compared to implants, respectively, at day 7 ( V.parvula , 6 × 10 5 vs 3 × 105 ; Milleri streptococci , 2 × 10 6 vs 6 × 10 5 ; Capnocytophaga spp., 2 × 10 6 vs 9 × 10 5 ; E.corrodens , 2 × 10 6 vs 5 × 10 5 ; N. mucosa , 2 × 10 6 vs 5 × 10 5 ; S.noxia , 2 × 10 6 vs 3 × 10 5 ; T.socranskii , 2 × 10 6 vs 5 × 10 5 ; H.alvei , 4 × 10 5 vs 2 × 10 5 ; and Neisseria spp., 6 × 10 5 vs 4 × 10 4 ), day 30 ( V.parvula , 5 × 10 5 vs 10 5 ; Capnocytophaga spp., 1.3 × 10 6 vs 6.8 × 10 4 ; F.periodonticum , 2 × 10 6 vs 10 6 ; S.noxia , 6 × 10 5 vs 2 × 10 5 ; H.alvei , 8 × 10 5 vs 9 × 10 4 ; and Neisseria spp., 2 × 10 5 vs 10 6 ), day 120 ( V.parvula , 8 × 10 5 vs 3 × 10 5 ; S.noxia , 2 × 10 6 vs 0; and T.socranskii , 3 × 10 5 vs 8 × 10 4 ), and day 180 ( S.enterica subsp. enterica serovar Typhi, 8 × 10 6 vs 2 × 10 6 ) (p<0.05). Implants showed significant increases over time in the levels of F.nucleatum , Gemella spp., H.pylori , P.micra , S.aureus , S.liquefaciens , and T.forsythia (p<0.05). LRA found that dental implants were negatively correlated with high levels of S. noxia and V. parvula (ß=-0.5 to -0.3; p<0.05). CONCLUSIONS: Early submucosal microbiota is diverse and only a few species differ between teeth and implants in the same individual. Only 7 days after implant installation, a rich microbiota can be found in the peri-implant site. After six months of evaluation, teeth and implants show similar prevalence and levels of the target species, including known and new periodontopathic species.

Transcriptomic Analyses of Neurotoxic Astrocytes Derived from Adult Triple Transgenic Alzheimer's Disease Mice.

Neurodegenerative diseases such as Alzheimer's disease have been classically studied from a purely neuronocentric point of view. More recent evidences support the notion that other cell populations are involved in disease progression. In this sense, the possible pathogenic role of glial cells like astrocytes is increasingly being recognized. Once faced with tissue damage signals and other stimuli present in disease environments, astrocytes suffer many morphological and functional changes, a process referred as reactive astrogliosis. Studies from murine models and humans suggest that these complex and heterogeneous responses could manifest as disease-specific astrocyte phenotypes. Clear understanding of disease-associated astrocytes is a necessary step to fully disclose neurodegenerative processes, aiding in the design of new therapeutic and diagnostic strategies. In this work, we present the transcriptomics characterization of neurotoxic astrocytic cultures isolated from adult symptomatic animals of the triple transgenic mouse model of Alzheimer's disease (3xTg-AD). According to the observed profile, 3xTg-AD neurotoxic astrocytes show various reactivity features including alteration of the extracellular matrix and release of pro-inflammatory and proliferative factors that could result in harmful effects to neurons. Moreover, these alterations could be a consequence of stress responses at the endoplasmic reticulum and mitochondria as well as of concomitant metabolic adaptations. Present results support the hypothesis that adaptive changes of astrocytic function induced by a stressed microenvironment could later promote harmful astrocyte phenotypes and further accelerate or induce neurodegenerative processes.

Colonization dynamics of subgingival microbiota in recently installed dental implants compared to healthy teeth in the same individual: a 6-month prospective observational study

Abstract Objectives To evaluate the colonization dynamics of subgingival microbiota established over six months around newly installed dental implants in periodontally healthy individuals, compared with their corresponding teeth. Methodology Seventeen healthy individuals assigned to receive single dental implants participated in the study. Subgingival biofilm was sampled from all implant sites and contralateral/ antagonist teeth on days 7, 30, 90, and 180 after implant installation. Microbiological analysis was performed using the Checkerboard DNA-DNA hybridization technique for detection of classical oral taxa and non-oral microorganisms. Significant differences were estimated by Mann-Whitney and Friedman tests, while associations between implants/teeth and target species levels were assessed by linear regression analysis (LRA). Significance level was set at 5%. Results Levels of some species were significantly higher in teeth compared to implants, respectively, at day 7 ( V.parvula , 6 × 10 5 vs 3 × 105 ; Milleri streptococci , 2 × 10 6 vs 6 × 10 5 ; Capnocytophaga spp., 2 × 10 6 vs 9 × 10 5 ; E.corrodens , 2 × 10 6 vs 5 × 10 5 ; N. mucosa , 2 × 10 6 vs 5 × 10 5 ; S.noxia , 2 × 10 6 vs 3 × 10 5 ; T.socranskii , 2 × 10 6 vs 5 × 10 5 ; H.alvei , 4 × 10 5 vs 2 × 10 5 ; and Neisseria spp., 6 × 10 5 vs 4 × 10 4 ), day 30 ( V.parvula , 5 × 10 5 vs 10 5 ; Capnocytophaga spp., 1.3 × 10 6 vs 6.8 × 10 4 ; F.periodonticum , 2 × 10 6 vs 10 6 ; S.noxia , 6 × 10 5 vs 2 × 10 5 ; H.alvei , 8 × 10 5 vs 9 × 10 4 ; and Neisseria spp., 2 × 10 5 vs 10 6 ), day 120 ( V.parvula , 8 × 10 5 vs 3 × 10 5 ; S.noxia , 2 × 10 6 vs 0; and T.socranskii , 3 × 10 5 vs 8 × 10 4 ), and day 180 ( S.enterica subsp. enterica serovar Typhi, 8 × 10 6 vs 2 × 10 6 ) (p<0.05). Implants showed significant increases over time in the levels of F.nucleatum , Gemella spp., H.pylori , P.micra , S.aureus , S.liquefaciens , and T.forsythia (p<0.05). LRA found that dental implants were negatively correlated with high levels of S. noxia and V. parvula (β=-0.5 to -0.3; p<0.05). Conclusions Early submucosal microbiota is diverse and only a few species differ between teeth and implants in the same individual. Only 7 days after implant installation, a rich microbiota can be found in the peri-implant site. After six months of evaluation, teeth and implants show similar prevalence and levels of the target species, including known and new periodontopathic species.

Radiosynthesis and validation of [18 F]fluoroestradiol in a Synthra plus research platform for use in routine clinical practice.

In this practitioner protocol, the optimization of the radiochemical synthesis of [18 F]fluoroestradiol (FES) on the Synthra RNplus research automated platform is described in detail and a quality control (QC) summary of three validation productions is presented. In comparison with published synthesis methods developed on other platforms, the yield was considerably improved (40%-45% ndc). The other important improvement is the reduction of the required concentration of H2 SO4 avoiding the production of high concentrations of acidic vapors that can deteriorate the module. Purification was achieved by solid phase extraction, and the required adaptation of an external heating plate to the module to evaporate the ethanol is also described. The product was obtained with high radiochemical purity and fulfilled all the requirements of current Good Manufacturing Practice (cGMP). The final product is formulated as a sterile, pyrogen-free solution suitable for human injection. To the best of our knowledge, this is the first report of FES production using this type of module.

Aplicación clínica del manejo de los recursos en crisis / Clinical aplication of resources in crisis managment

Las situaciones de crisis en la sala de operaciones son eventos poco frecuentes, con personal trabajando rápido y bajo presión, intentando sobrellevar el incidente con los menores riesgos para el paciente. Se expone un caso clínico en el marco del trabajo de una unidad de anestesia para cirugía de tórax en la cual se presenta una crisis asistencial abordada por un equipo de trabajo capacitado mediante simulación en la aplicación de la herramienta de "Manejo de los Recursos en Crisis (CRM)". Planteamos que la aplicación de esta herramienta por un equipo capacitado en su utilización contribuyó al éxito y buena evolución de un paciente crítico.

Crisis situations on the operation room seldom happen, with staff working fast and under pressure, trying to overcome the incident at the same time as reducing the risks for the patient. Here we expose a clinical case on the frame of work of an anesthesia unit assembled for thorax surgery during which an asistential crisis occurs and is managed by a group of coworkers trained by means of simulation on the appliance of the tool called "Crisis Resource Management (CRM)". We support the idea that the appliance of this tool by a team of professionals trained on its use, contributed to the success and good evolution on a critical patient.

Tratamento da peri-implantite com emprego de L-PRF: relato de caso clínico / Peri-implantitis treatment with adjunctive use of L-PRF: case report

Com o aumento do número de indivíduos reabilitados com implantes dentários, novas complicações clínicas estão surgindo, incluindo as doenças peri-implantares. Várias terapias conservadoras e cirúrgicas têm sido propostas para o tratamento da peri-implantite. Estas abordagens cirúrgicas podem ser complementadas com métodos regenerativos, nos quais poderiam ser englobadas as terapias com fibrina rica em plaquetas e leucócitos (L-PRF). Objetivo: O objetivo deste estudo é relatar um caso clínico de peri-implantite tratado com o emprego de L-PRF após 12 meses a partir da intervenção. Relato de caso: O paciente relatado apresentava três implantes instalados há 9 anos, que apresentavam médias de profundidade de sondagem e de nível clínico de inserção de 3,1 e 2,7 mm, respectivamente. O tratamento da peri-implantite consistiu em desbridamento com instrumentos manuais através de acesso cirúrgico e irrigados com clorexidina a 0,12%. Após estes procedimentos, os implantes receberam membrana de fibrina obtidas com a técnica para L-PRF. Após 12 meses, foi constatado redução das bolsas peri-implantares com redução de profundidade de sondagem para 2,3 mm e de nível clínico de inserção para 2 mm. No exame radiográfico, foi possível observar sinais radiográficos indicativos de preenchimento dos defeitos ósseos. Conclusão: O tratamento utilizado para tratar o caso de peri-implantite relatado, mecânico com acesso cirúrgico e uso de L-PRF, apresentou bons resultados clínicos e radiográficos aos 12 meses (AU)

Along with the increasing number of subjects receiving dental implants, new clinical complications are emerging, including peri-implant diseases. Different conservative techniques are being proposed to treat peri-implantitis. Such approaches include regenerative methods, in which leucocyte - and platelet - rich fibrin (L-PRF) is one of them. Aim: The aim of this study is to present a follow up of a clinical case of peri-implantitis treated with the use of L-PRF. Case report: The individual in this report had three dental implants installed 9 years before, presenting mean probing depth and clinical attachment level of 3.1 and 2.7 mm, respectively. The peri-implantitis treatment was performed by debridement of implants with manual instruments in a surgical approach, and irrigation with 0.12% chlorhexidine. After, implants received fibrin membrane obtained using the L-PRF method. At the 12 months follow up, it was observed a reduction in the probing depth and the clinical attachment level to 2.3 mm and 2 mm, respectively. Radiographic examinations showed indications of bone defect filling. Conclusion: The employed treatment to treat periimplantitis, mechanical with surgical approach and use of L-PRF, showed good clinical and radiographic results at 12 months of observation.(AU)

Embarazo ectópico en cicatriz de cesárea. Reporte de caso / Ectopic pregnancy in caesarian scar. A case report

Presentamos un caso que se reporta en la literatura médica como embarazo ectópico en cicatriz de cesárea. Esta paciente consultó por sangrado vaginal y hematuria asociados a embarazo de 12 semanas; la ecografía reportó pérdida de la relación placentamiometrio en pared ístmica anterior. El manejo se hizo mediante una histerectomía abdominal. El abordaje actual más aceptado es conservador, sin embargo unas guías de tratamiento universal no han podido ser establecidas

Attributable cost and length of stay for patients with central venous catheter-associated bloodstream infection in Mexico City intensive care units: a prospective, matched analysis.

BACKGROUND: No information is available about the financial impact of central venous catheter (CVC)-associated bloodstream infection (BSI) in Mexico. OBJECTIVE: To calculate the costs associated with BSI in intensive care units (ICUs) in Mexico City. DESIGN: An 18-month (June 2002 through November 2003), prospective, nested case-control study of patients with and patients without BSI. SETTING: Adult ICUs in 3 hospitals in Mexico City. PATIENTS AND METHODS: A total of 55 patients with BSI (case patients) and 55 patients without BSI (control patients) were compared with respect to hospital, type of ICU, year of hospital admission, length of ICU stay, sex, age, and mean severity of illness score. Information about the length of ICU stay was obtained prospectively during daily rounds. The daily cost of ICU stay was provided by the finance department of each hospital. The cost of antibiotics prescribed for BSI was provided by the hospitals' pharmacy departments. RESULTS: For case patients, the mean extra length of stay was 6.1 days, the mean extra cost of antibiotics was US dollars 598, the mean extra hospital cost was US dollars 11,591, and the attributable extra mortality was 20%. CONCLUSIONS: In this study, the duration of ICU stay for patients with central venous catheter-associated BSI was significantly longer than that for control patients, resulting in increased healthcare costs and a higher attributable mortality. These conclusions support the need to implement preventive measures for hospitalized patients with central venous catheters in Mexico.

Device-associated nosocomial infection rates in intensive care units in four Mexican public hospitals.

BACKGROUND: Routine surveillance of nosocomial infections has become an integral part of infection control and quality assurance in US hospitals. METHODS: As part of the International Nosocomial Infection Control Consortium, we performed a prospective nosocomial infection surveillance cohort study in 5 adult intensive care units of 4 Mexican public hospitals using the Centers for Disease Control and Prevention National Nosocomial Infections Surveillance system definitions. Site-specific nosocomial infection rates were calculated. RESULTS: The overall nosocomial infection rate was 24.4% (257/1055) and 39.0 (257/6590) per 1000 patient days. The most common infection was catheter-associated bloodstream infection, 57.98% (149/257), followed by ventilator-associated pneumonia, 20.23% (52/257), and catheter-associated urinary tract infection, 21.79% (56/257). The overall rate of catheter-associated bloodstream infections was 23.1 per 1000 device-days (149/6450); ventilator-associated pneumonia rate was 21.8 per 1000 device-days (52/2390); and catheter-associated urinary tract infection rate was 13.4 per 1000 device-days (56/4184). CONCLUSION: Our rates are similar to other hospitals of Latin America and higher than US hospitals.

The effect of process control on the incidence of central venous catheter-associated bloodstream infections and mortality in intensive care units in Mexico.

PURPOSE: To ascertain the effect of an infection control program including process control on intensive care unit (ICU) rates of intravascular device (IVD)-associated bloodstream infection (BSI). SETTING: Two level III adult ICUs in one public university hospital in Mexico: one medical surgical ICU and one neurosurgical ICU. POPULATION STUDY: All adult patients admitted to study units who had a central venous catheter (CVC) in place for at least 24 hrs. METHODS: A prospective before/after trial in which rates of IVD-associated BSI are determined during a period of active surveillance without process control (phase 1) were compared with rates of IVD-associated BSI after implementing an infection control program applying process control (phase 2). RESULTS: Six hundred five IVD-days were accumulated in phase 1, and 2824 IVD-days were accumulated during phase 2. Compliance with CVC site care and hand hygiene improved significantly from baseline during the study period: placing a gauze dressing over the catheter insertion site (99.24% vs. 86.69%, respectively; relative risk [RR] = 1.14; 95% confidence interval [CI] = 1.07-1.22; p = .0000), proper use of gauze for vascular catheter insertion site (97.87% vs. 84.21%, respectively; RR = 1.16; 95% CI = 1.09-1.24; p = .0000), documentation of the duration of the administration set of the vascular catheter (93.85% vs. 40.69%, respectively; RR = 2.34; 95% CI = 2.14-2.56; p = .0000), and hand hygiene before contact with the patient (84.9% vs. 62%, respectively; RR = 1.37; 95% CI = 1.21-1.51; p = .0000). Overall rates of IVD-associated BSI were lowered significantly from baseline rates after implementation of process control (19.5 vs. 46.3 BSIs per 1000 IVD-days, respectively; RR = 0.42; 95% CI = 0.27-0.66; p = .0001). Overall rates of crude unadjusted mortality were lowered significantly from baseline rates (48.5% vs. 32.8% per 100 discharges, respectively; RR = 0.68; 95% CI = 0.50-0.31; p = .01). CONCLUSION: Implementation of an infection control program utilizing education, process control, and performance feedback was associated with significant reductions in rates of IVD-associated BSI and mortality.

Vigencia de la transferencia intratubaria de gametos (G.I.F.T.) en el momento actual / Standing of G.I.F.T. in the present moment

Hemos analizado los resultados obtenidos en 180 ciclos consecutivos de 131 pacientes en las que se realizó una transferencia intratubaria de gametos entre los años 1993-1996 en el Instituto de Ginecología y Fertilidad (IFER). La edad promedio de las mismas era de 33,8ñ4,1 años, siendo de 28,7ñ5,4 en las menores de 37 años y de 39,2ñ2,1 en las mayores de 37 años. El promedio de años de esterilidad era de 4,1ñ2,8 años, siendo el tiempo de esterilidad de 3,8ñ2,5 en las menores de 37 años y de 4,6ñ3,2 en las de edad mayor o igual a 37 años. Las causas por las que se realizó el procedimiento fueron: 45 ciclos de endometriosis, 40 de esterilidad sin causa aparente, 30 de factor masculino, 24 de factor tubo peritoneal y 26 de síndrome de ovario poliquístico. El porcentaje de embarazos global fue de 35,7 por ciento por ciclo de captación con un 16,9 por ciento de abortos y un porcentaje de nacidos vivos de 29,7 por ciento, con un 23,7 de embarazos múltiples y un 1,6 de embarazos ectópicos. El índice de implantación fue del 12 por ciento. Los resultados obtenidos más los datos aportados por la bibliografía nos permiten sostener que este procedimiento mantiene su vigencia al momento actual, en todas las indicaciones de infertilidad a excepción del factor masculino severo, siendo la edad de las pacientes un factor importante en el logro de embarazos

Vigencia de la transferencia intratubaria de gametos (G.I.F.T.) en el momento actual / Standing of G.I.F.T. in the present moment

Hemos analizado los resultados obtenidos en 180 ciclos consecutivos de 131 pacientes en las que se realizó una transferencia intratubaria de gametos entre los años 1993-1996 en el Instituto de Ginecología y Fertilidad (IFER). La edad promedio de las mismas era de 33,8ñ4,1 años, siendo de 28,7ñ5,4 en las menores de 37 años y de 39,2ñ2,1 en las mayores de 37 años. El promedio de años de esterilidad era de 4,1ñ2,8 años, siendo el tiempo de esterilidad de 3,8ñ2,5 en las menores de 37 años y de 4,6ñ3,2 en las de edad mayor o igual a 37 años. Las causas por las que se realizó el procedimiento fueron: 45 ciclos de endometriosis, 40 de esterilidad sin causa aparente, 30 de factor masculino, 24 de factor tubo peritoneal y 26 de síndrome de ovario poliquístico. El porcentaje de embarazos global fue de 35,7 por ciento por ciclo de captación con un 16,9 por ciento de abortos y un porcentaje de nacidos vivos de 29,7 por ciento, con un 23,7 de embarazos múltiples y un 1,6 de embarazos ectópicos. El índice de implantación fue del 12 por ciento. Los resultados obtenidos más los datos aportados por la bibliografía nos permiten sostener que este procedimiento mantiene su vigencia al momento actual, en todas las indicaciones de infertilidad a excepción del factor masculino severo, siendo la edad de las pacientes un factor importante en el logro de embarazos (AU)