The Use of a Theory of Change Model to Guide the Implementation of a Comprehensive Surgical Specialty Training Program in Equatorial Guinea.

Background: Equatorial Guinea (EG) is located on the African west coast, with only 0.4 trained physicians per 1,000 resident population. The country has one medical school and there is no specialist training program. From 2000 to 2022, 524 doctors have received their medical degree. However, the number of national surgical specialists in the entire country is currently 42. Objective: Formación Especializada Sanitaria en Guinea Ecuatorial (FES Guinea) is a program specifically aimed at designing and implementing a long-term national surgical specialist training program. Methods: Más Que Salud (+QS), which means "More than Health" in Spanish, is a nonprofit organization leading the FES Guinea program. We used the theory of change (ToC) framework to evaluate the work accomplished and implement subsequent phases. The initial phase (A) included a needs assessment and mapping of available resources. An intermediate phase (B) started with a memorandum of understanding to implement a Train the Trainer program. The consolidation phase (C) consists of educational interventions and future advanced training projects. Findings: The ToC model allowed us an analyses of initial and intermediate phases. The needs assessments and resources mapping were executed while several scientific meetings and workshops were given. Scholarships to support specialist training abroad benefited six physicians in a diverse set of surgical disciplines. A regulatory commission to implement the FES Guinea program and the National Medical Council of EG were created. Working directly with the EG Ministry of Health, +QS codesigned a National Health Development Plan that began implementation in 2021 to continue until 2025. Conclusions: The ToC model allowed us to predict the current and future potential effects of FES Guinea on surgical workforce development in EG. This is a unique surgical training program, which combined effective initiatives spearheaded initially by an NGO that successfully incorporated both local health and academic authorities, ensuring sustainability.

Inactivation of Avian Influenza Virus Inoculated into Ground Beef Patties Cooked on a Commercial Open-Flame Gas Grill.

With the emergence of clade 2.3.4.4b H5N1 highly pathogenic avian influenza virus (AIV) infection of dairy cattle and its subsequent detection in raw milk, coupled with recent AIV infections affecting dairy farm workers, experiments were conducted to affirm the safety of cooked ground beef related to AIV because such meat is often derived from cull dairy cows. Specifically, retail ground beef (percent lean:fat = ca. 80:20) was inoculated with a low pathogenic AIV (LPAIV) isolate to an initial level of 5.6 log10 50% egg infectious doses (EID50)  per 300 g patty. The inoculated meat was pressed into patties (ca. 2.54 cm thick, ca. 300 g each) and then held at 4 °C for up to 60 min. In each of the two trials, two patties for each of the following three treatments were cooked on a commercial open-flame gas grill to internal instantaneous temperatures of 48.9 °C (120°F), 62.8 °C (145°F), or 71.1 °C (160°F), but without any dwell time. Cooking inoculated ground beef patties to 48.9 °C (ave. cooking time of ca. 15 min) resulted in a mean reduction of ≥2.5 ± 0.9 log10 EID50 per 300 g of ground beef as assessed via quantification of virus in embryonating chicken eggs (ECEs). Likewise, cooking patties on a gas grill to 62.8 °C (ave. cooking time of ca. 21 min) or to the USDA FSIS recommended minimum internal temperature for ground beef of 71.1 °C (ave. cooking time of ca. 24 min) resulted in a reduction to nondetectable levels from initial levels of ≥5.6 log10 EID50 per 300 g. These data establish that levels of infectious AIV are substantially reduced within inoculated ground beef patties (20% fat) using recommended cooking procedures.

Polyphasic Approach and Potential Cyanotoxin Production by Planktothrix from the Río Grande de Comitán and Montebello Lakes National Park, Southern Mexico.

The development of anthropic activities during recent years has led to an increase in nutrient fluxes in the Río Grande de Comitán and Montebello Lakes National Park, Mexico. In turn, this has modified the dynamics of the biotic community, specifically favoring the presence of cyanobacteria tolerant to contamination. The continual and massive presence of Planktothrix species (spp.) in the system suggests a potential detrimental impact for economic issues and human health. In this study, we identify the morphological and molecular characteristics of Planktothrix populations from seven tropical (1,380-1,740 masl, 23.0-25.5°C) and calcareous lakes and two ponds from a water treatment plant. We also assess the ecological drivers that could be related to the presence of cyanotoxins in the system. The ecological preferences, morphology, 16S rRNA structure, and 16S-23S rRNA internal transcribed spacer found evidence for three species: P. agardhii distributed in neutral to slightly basic water (pH = 7.7-8.7), and P. spiroides and Planktothrix sp. in alkaline waters (pH = 9.1). The presence of the mcyE gene and its validation by liquid chromatography confirmed the presence of two microcystin variants (MC-RR and MC-LR) in at least three populations of P. agardhii. These microcystins put the health of the ecosystem and its inhabitants at risk, a condition that should be addressed and resolved with a water management and detoxification strategy in the basin.

Biosynthesis of natural and halogenated plant monoterpene indole alkaloids in yeast.

Monoterpenoid indole alkaloids (MIAs) represent a large class of plant natural products with marketed pharmaceutical activities against a wide range of indications, including cancer, malaria and hypertension. Halogenated MIAs have shown improved pharmaceutical properties; however, synthesis of new-to-nature halogenated MIAs remains a challenge. Here we demonstrate a platform for de novo biosynthesis of two MIAs, serpentine and alstonine, in baker's yeast Saccharomyces cerevisiae and deploy it to systematically explore the biocatalytic potential of refactored MIA pathways for the production of halogenated MIAs. From this, we demonstrate conversion of individual haloindole derivatives to a total of 19 different new-to-nature haloserpentine and haloalstonine analogs. Furthermore, by process optimization and heterologous expression of a modified halogenase in the microbial MIA platform, we document de novo halogenation and biosynthesis of chloroalstonine. Together, this study highlights a microbial platform for enzymatic exploration and production of complex natural and new-to-nature MIAs with therapeutic potential.

Acidosis induces RIPK1-dependent death of glioblastoma stem cells via acid-sensing ion channel 1a.

Eliciting regulated cell death, like necroptosis, is a potential cancer treatment. However, pathways eliciting necroptosis are poorly understood. It has been reported that prolonged activation of acid-sensing ion channel 1a (ASIC1a) induces necroptosis in mouse neurons. Glioblastoma stem cells (GSCs) also express functional ASIC1a, but whether prolonged activation of ASIC1a induces necroptosis in GSCs is unknown. Here we used a tumorsphere formation assay to show that slight acidosis (pH 6.6) induces necrotic cell death in a manner that was sensitive to the necroptosis inhibitor Nec-1 and to the ASIC1a antagonist PcTx1. In addition, genetic knockout of ASIC1a rendered GSCs resistant to acid-induced reduction in tumorsphere formation, while the ASIC1 agonist MitTx1 reduced tumorsphere formation also at neutral pH. Finally, a 20 amino acid fragment of the ASIC1 C-terminus, thought to interact with the necroptosis kinase RIPK1, was sufficient to reduce the formation of tumorspheres. Meanwhile, the genetic knockout of MLKL, the executive protein in the necroptosis cascade, did not prevent a reduction in tumor sphere formation, suggesting that ASIC1a induced an alternative cell death pathway. These findings demonstrate that ASIC1a is a death receptor on GSCs that induces cell death during prolonged acidosis. We propose that this pathway shapes the evolution of a tumor in its acidic microenvironment and that pharmacological activation of ASIC1a might be a potential new strategy in tumor therapy.

Integrated multi-modality image-guided navigation for neurosurgery: open-source software platform using state-of-the-art clinical hardware.

PURPOSE: Image-guided surgery (IGS) is an integral part of modern neuro-oncology surgery. Navigated ultrasound provides the surgeon with reconstructed views of ultrasound data, but no commercial system presently permits its integration with other essential non-imaging-based intraoperative monitoring modalities such as intraoperative neuromonitoring. Such a system would be particularly useful in skull base neurosurgery. METHODS: We established functional and technical requirements of an integrated multi-modality IGS system tailored for skull base surgery with the ability to incorporate: (1) preoperative MRI data and associated 3D volume reconstructions, (2) real-time intraoperative neurophysiological data and (3) live reconstructed 3D ultrasound. We created an open-source software platform to integrate with readily available commercial hardware. We tested the accuracy of the system's ultrasound navigation and reconstruction using a polyvinyl alcohol phantom model and simulated the use of the complete navigation system in a clinical operating room using a patient-specific phantom model. RESULTS: Experimental validation of the system's navigated ultrasound component demonstrated accuracy of [Formula: see text] and a frame rate of 25 frames per second. Clinical simulation confirmed that system assembly was straightforward, could be achieved in a clinically acceptable time of [Formula: see text] and performed with a clinically acceptable level of accuracy. CONCLUSION: We present an integrated open-source research platform for multi-modality IGS. The present prototype system was tailored for neurosurgery and met all minimum design requirements focused on skull base surgery. Future work aims to optimise the system further by addressing the remaining target requirements.

Protection against Different Genotypes of Newcastle Disease Viruses (NDV) Afforded by an Adenovirus-Vectored Fusion Protein and Live NDV Vaccines in Chickens.

The efficacy of an adenovirus-vectored Newcastle disease virus (NDV) vaccine expressing the fusion (F) NDV protein (adeno-F) was evaluated against challenges with virulent heterologous and homologous NDV strains to the F protein. In a preliminary study, two different doses (low and high) of adeno-F were tested against a virulent NDV strain containing the homologous NDV F protein, CA02. In a second study, at three weeks post-vaccination, the efficacy of the high dose of adeno-F was compared to a live attenuated NDV vaccine strain (LaSota) against three antigenically distinct virulent NDV challenge strains, one homologous (CA02) and two heterologous (TZ12, EG14) to F in the vectored vaccine. In both experiments, clinical signs, mortality, virus shedding, and humoral response were evaluated. In the first experiment, the survival rates from birds vaccinated with adeno-F at a high and low dose were 100% and 25%, respectively. In the second experiment, birds vaccinated with the high dose of adeno-F had a survival rate of 80%, 75%, and 65% after challenge with the CA02, TZ12, and EG14 viruses, respectively. All of the LaSota-vaccinated birds survived post-challenge no matter the NDV challenge strain. High antibody titers were detected after vaccination with LaSota by HI and ELISA tests. The majority of adeno-F-vaccinated birds had detectable antibodies using the ELISA test, but not using the HI test, before the challenge. The data show that both the similarity of the F protein of the adeno-F vaccine to the challenge virus and the adeno-F vaccination dose affect the efficacy of an adenovirus-vectored NDV vaccine against a virulent NDV challenge.

Reparación quirúrgica inmediata de la ruptura del tendón del pectoral mayor causada por levantamiento de pesas. Reporte de caso / Immediate surgical repair of pectoralis major tendon rupture caused by weightlifting. Case Report

La ruptura del tendón del músculo pectoral mayor es un evento raro para el cual está indicado la reparación quirúrgica en pacientes jóvenes y atléticos. La reparación puede hacerse de forma aguda o crónica, hasta o despúes de 8 semanas, respectivamente. Las reparaciones agudas han demostrado excelentes resultados, sin embargo, hasta el momento no se encuentran reportes de reparaciones quirúrgicas dentro de las primera 24 horas de la lesíon. Presentamos un caso de reparación quirúrgica inmediata de una ruptura del tendón del músculo pectoral mayor en un hombre de 45 años sin antecedentes de uso de esteroides, que ocurrió mientras levantaba pesas. El diagnóstico inmediato se confirmó con una RM de emergencia más la evaluación clínica. La intervención quirúrgica se realizó en menos de 24 horas. Se instauró un protocolo de rehabilitación gradual con ejercicios pasivos. Seis meses después de la cirugía, se encontró recuperación de la amplitud de movimiento y la fuerza del hombro, así como la restauración anatómica completa. Concluimos que la reparación quirúrgica precoz de una ruptura del tendón del músculo pectoral mayor, el primer día de la lesión, en menos de 24 horas, acompañada de una buena técnica quirúrgica y un protocolo de rehabilitación gradual, arrojó excelentes resultados seis meses después del trauma, similares a los reportados en la literatura para reparaciones agudas (<6 semanas). Nivel de evidencia: Nivel IV

The rupture of the pectoralis major muscle tendon in young and athletic patients is a rare event for which surgical repair is indicated. The repair can be acute or chronic, up to or after 8 weeks, respectively. Acute repair has shown excellent results, and so far there are no reports of surgical repairs within the first 24hours of the injury. A case is presented of the immediate surgical repair of a ruptured pectoralis major muscle tendon occurring in a 45-year-old man with no history of steroid use, while lifting weights. The immediate diagnosis was confirmed with an emergency MRI plus clinical evaluation. The surgical intervention was performed in less than 24hours. A protocol of gradual rehabilitation with passive exercises was established. Six months after surgery, there was recovery of range of motion and shoulder strength, as well as complete anatomical restoration. It is concluded that early surgical repair of a rupture of the pectoralis major muscle tendon on the first day of the injury, or in less than 24hours, accompanied by a good surgical technique and a gradual rehabilitation protocol, yielded excellent results six months after the trauma, similar to that reported in the literature for acute repairs. Evidence level: Level IV

Fracturas inestables de radio distal intra y extraarticulares: análisis comparativo de resultados a mediano plazo del tratamiento quirúrgico con placas volares / Intra- and extra-articular distal radius unstable fractures: comparative analysis of the medium-term results of volar plate surgical treatment

Introducción Comparar los resultados radiológicos y recuperación postoperatoria de la función de la muñeca a mediano plazo en las fracturas inestables extra e intra articulares de radio distal, después de la reducción abierta con abordaje palmar y osteosíntesis con placa volar. Materiales y métodos Estudio de casos y controles en 52 pacientes divididos en los grupos de fracturas extra o intra articulares de acuerdo a la clasificación AO. Las radiografías preoperatorias y postoperatorias fueron evaluadas para determinar la restauración anatómica de la longitud radial, ángulo radial e inclinación palmar del radio. Se evaluó además el resultado, seis meses después de la cirugía, del rango activo de movimiento y la fuerza de agarre, a la vez, que se hizo evaluación del puntaje de QuickDASH. Resultados La edad promedio fue 53,7±16,8 (DE) años; el 63% mujeres. Las fracturas extra articulares fueron más frecuentes en las mujeres, pero las intra articulares presentaron distribución similar por sexo (p=0.023). La fuerza de agarre de la mano operada fue 73.7% y 67.5% de la mano opuesta en las fracturas extra e intra articulares, respectivamente. El puntaje QuickDASH promedio fue 2.36 (DE 2.01) y 4.16 (DE 3.82) en fracturas extra e intra articulares respectivamente (p=0.111). Discusión Para fracturas de radio distal la reducción abierta con abordaje palmar y estabilización con placa volar ofrece resultados funcionales satisfactorios tanto para las fracturas extra articulares como para las intra articulares, con una leve, aunque esperada, ventaja en las primeras debido a su menor complejidad.

Background To examine and compare the radiological results and postoperative recovery of the medium-term wrist function in unstable extra- and intra-articular fractures of distal radius, after open reduction with a palmar approach and osteosynthesis with a volar plate. Materials and methods Retrospective case control study in 52 patients, divided into groups according to the Orthopaedic Association (AO) classification as extra- or intra-articular fractures. The pre-operative and post-operative radiographs were evaluated to determine the anatomical restoration of the radial length, radial angle, and palmar inclination of the radius. The medium-term results of the active range of motion and the grip strength, as well as the Quick DASH score, were evaluated six months after surgery. Results The mean age was 53.7±16.8 (SD) years and 63% were women. Extra-articular fractures were more frequent in women, but intra-articular fractures had a similar distribution by gender (P=.023). The grip strength of the operated hand was 73.7% and 67.5% of the opposite hand in the extra- and intra-articular fractures, respectively. The mean Quick DASH score was 2.36 (SD 2.01) and 4.16 (SD 3.82) in extra- and intra-articular fractures, respectively (P=.111). Discussion For unstable distal radius fractures, open reduction with palmar approach and volar plate stabilisation offers satisfactory functional results for both extra-articular and intra-articular fractures, with a slight, but expected, advantage in the former due to its lesser complexity.

Caracterización clínica e histopatológica de niños con hepatitis autoinmune en un centro de referencia de Bogotá, Colombia / Clinical and histopathological characterization of children with autoimmune hepatitis at a referral center in Bogotá, Colombia

Resumen La hepatitis autoinmune (HAI) es una enfermedad hepática inflamatoria progresiva poco frecuente en niños y adolescentes, la cual es un reto diagnóstico para clínicos y patólogos. Describimos las características clínicas, bioquímicas e histopatológicas de 21 pacientes pediátricos con HAI diagnosticados en los últimos 14 años. Las biopsias hepáticas se reevaluaron para analizar detalladamente los hallazgos histopatológicos. De los 21 casos evaluados, 12 (57,1%) fueron mujeres, la mediana de edad fue 14 años, y 17 (80,9%) tenían HAI tipo 1. Los signos clínicos más frecuentes fueron ictericia (66,7%) y coluria (44,4%); también hubo evidencia de hipertensión portal con várices esofágicas (47,1%) y esplenomegalia (41,2%). El 11,8% de los pacientes tenía antecedentes de otras enfermedades autoinmunes. El 89,5%, 88,9% y 60,0% de los casos tenía elevación de aminotransferasas, hiperbilirrubinemia y bajos niveles de albúmina sérica, respectivamente. Las biopsias reevaluadas mostraron infiltrado linfoplasmocitario portal (94,4%), hepatitis de interfase (77,8%) y formación de rosetas (50,0%). En el 42,9% de las biopsias se hallaron inclusiones hialinas en las células de Kupffer. Cerca del 33,5% de los casos mostró cirrosis en la biopsia inicial. A pesar del tratamiento inmunosupresor, 4 pacientes requirieron trasplante hepático y 2 están en lista de espera. La HAI en niños puede manifestarse con ictericia y coluria, signos de hipertensión portal, aminotransferasas elevadas, hiperbilirrubinemia y anticuerpos circulantes. Las inclusiones hialinas en las células de Kupffer pueden ser un hallazgo útil en el diagnóstico histopatológico de la HAI en niños.

Abstract Autoimmune hepatitis (AIH) is a progressive inflammatory liver disease. It is uncommon in children and adolescents, and is a diagnostic challenge for clinicians and pathologists. We describe the clinical, biochemical and histopathological characteristics of 21 pediatric patients with AIH diagnosed in the last 14 years. Liver biopsies were reassessed to analyze histopathological findings in detail. Of the 21 cases evaluated, 12 (57.1%) were girls and young women, the median age was 14 years old, and 17 (80.9%) had type 1 AIH. The most frequent clinical signs were jaundice (66.7%), choluria (44.4%), evidence of portal hypertension with esophageal varices (47.1%), and splenomegaly (41.2%). Histories of other autoimmune diseases were found in 11.8% of these patients. Elevated levels of aminotransferases were found in 89.5% of the patients, hyperbilirubinemia was found in 88.9%, and 60.0% of the cases had low levels of serum albumin. Reassessed biopsies showed portal lymphoplasmocytic infiltrate (94.4%), interface hepatitis (77.8%) and rosette formation (50.0%). Hyaline inclusions were found in Kupffer cells in 42.9% of the biopsies. About 33.5% of the cases showed cirrhosis at the initial biopsy. Despite immunosuppressive treatment, four patients required liver transplantation and two are on the waiting list. AIH in children can manifest with jaundice, choluria, signs of portal hypertension, elevated aminotransferases, hyperbilirubinemia and circulating antibodies. Hyaline inclusions in Kupffer cells may be a useful finding in the histopathological diagnosis of AIH in children.

Bilateral Macrodactyly of the Halluces in an Adolescent Girl Corrected with Shortening Osteotomies of the First Metatarsal and the Phalangeal Bones: A Case Report.

CASE: A 14-year-old girl presented with painful high-arched feet and unusual, asymptomatic, bilateral macrodactyly of the halluces. After a year of observation, a surgical reduction was performed because of the psychological effect that the abnormality had on the patient. Bilateral shortening osteotomies of the metatarsal and the proximal phalangeal bones were performed. At 2 months after surgery, complete bone healing and alignment had been achieved. At the 5-year follow-up, we noted fully functional big toes, plantigrade feet, bilateral proper toe formula, and extreme patient satisfaction with the cosmetic results. CONCLUSION: Dual osteotomies for toe shortening in a patient with bilateral nondysmorphic macrodactyly provided appropriate length reduction and satisfactory aesthetic and functional results.

"One-Shot" CT image navigated circumferential fusion in a single lateral decubitus position: surgical technique.

The purpose of this paper was to summarize the surgical peculiarities of a combined approach for minimally invasive lateral retroperitoneal interbody fusion and posterior percutaneous pedicle screw instrumentation in the same lateral decubitus position using intraoperative computed tomography-based navigation.

Histopathologic Characterization and Shedding Dynamics of Guineafowl (Numida meleagris) Intravenously Infected with a H6N2 Low Pathogenicity Avian Influenza Virus.

Guineafowl of different ages were inoculated intravenously with a H6N2 wild waterfowl-origin low pathogenicity avian influenza virus (LPAIV). No clinical disease was observed. The infected birds had atrophy of the spleen, thymus, and cloacal bursa when compared with the noninfected control groups. The central and peripheral lymphoid tissues presented either lymphoproliferative or degenerative lesions that increased in intensity from 14 to 21 days postinoculation (DPI). Lymphoid depletion was present in the bursa, thymic lobes, and spleen T-dependent zone. In contrast, lymphoid proliferation was observed in liver, pancreas, and spleen B-dependent zone. Bronchus associated lymphoid tissue hyperplasia was observed in the lungs of the birds at 14 and 21 DPI. The virus was detected by virus isolation and reverse transcription PCR from both oropharyngeal and cloacal swabs with higher isolation rates from the latter. Most birds from the LPAIV inoculated groups shed virus up to 7 DPI. The virus was infrequently isolated from lung, kidney, liver, bursa, or spleen of infected birds until 14 DPI and from two samples (kidney and spleen, 1-yr-old birds) at 21 DPI. These data indicate that the wild bird-origin LPAIV used in this study caused pantropic infection in guineafowl when inoculated intravenously.

Prevalence of severe esophagitis in Spain. Results of the PRESS study (Prevalence and Risk factors for Esophagitis in Spain: A cross-sectional study).

BACKGROUND: *N.P. and M.P. contributed equally to this study.The current prevalence of esophagitis in southern Europe is unknown. In addition, the risk factors for reflux esophagitis are not fully understood. OBJECTIVE: The objective of this article is to assess the prevalence and risk factors for esophagitis in Spain. METHODS: A prospective, observational, cross-sectional, multicenter study (PRESS study) was conducted among 31 gastrointestinal endoscopy units throughout Spain. A total of 1361 patients undergoing upper gastrointestinal endoscopy were enrolled. Sociodemographic, clinical and treatment data were recorded. RESULTS: A total of 95% of patients were Caucasian and 52% were male (mean age: 53 ± 17 years). The most frequent symptoms prompting endoscopy were heartburn (40%), regurgitation (26%) and dysphagia (15%). Fifty-four percent of patients undergoing endoscopy were receiving proton pump inhibitor (PPI) treatment. Esophagitis (mainly mild-moderate) was present in 154 (12.4%) patients. The severe form was recorded in only 11 (0.8%) patients. Multivariate analysis results indicated that the likelihood of esophagitis was higher in men (OR = 1.91, 95% CI = 1.31-2.78), in patients with high GERD-Q scores (OR = 1.256, 95% CI = 1.176-1.343), weight increase (OR = 1.014, 95% CI = 1.003-1.025) and high alcohol consumption (OR = 2.49, 95% CI = 1.16-5.36). CONCLUSION: Severe esophagitis is a rare finding in the Spanish population. Male gender, high GERD-Q score, weight increase and high alcohol consumption are main risk factors for its appearance.

Effects of resveratrol on ovarian response to controlled ovarian hyperstimulation in ob/ob mice.

OBJECTIVE: To evaluate antidiabetic and anti-inflammatory effects of resveratrol on the ovarian response to controlled ovarian hyperstimulation (COH) in obesity-related infertility. DESIGN: Experimental. SETTING: University laboratory. ANIMAL(S): Sixteen female ob/ob mice and 16 female C57BL/6J mice undergoing COH. INTERVENTION(S): Wild-type placebo group; wild-type resveratrol group; ob/ob mice placebo group; ob/ob mice resveratrol group. Resveratrol 3.75 mg/kg daily for 20 days and undergoing COH protocol. MAIN OUTCOME MEASURE(S): Body and reproductive system weight, food intake, fasting blood glucose, plasma insulin and T levels, and Homeostatic Index of Insulin Resistance; interleukin-6 and tumor necrosis factor-α levels in adipose tissue by Western blot; assessment of quality and quantity of oocytes retrieved; and quantitative analysis of ovarian follicles. RESULT(S): Plasma insulin and T levels decreased and Homeostatic Index of Insulin Resistance improved in ob/ob mice treated with resveratrol. Interleukin-6 and tumor necrosis factor-α levels were significantly reverted back to near normalcy after resveratrol treatment in obese mice. Administration of resveratrol resulted in a significantly higher number of oocytes collected in wild-type mice. The number of primary, growing, preovulatory, and atretic follicles was found to be decreased in the group of obese mice treated with resveratrol when compared with the obese control group. CONCLUSION(S): Resveratrol administration could exert benefits against loss of ovarian follicles, and these actions may be mediated, at least in part, via anti-inflammatory, insulin-sensitizing, and antihyperandrogenism effects. These observations further validate the therapeutic potential of resveratrol to preserve ovarian reserve in conditions associated with obesity. Our results suggest the possible clinical use of resveratrol to enhance the ovarian response to COH in normal-weight females.

Pseudomonas aeruginosa isolates in severe chronic obstructive pulmonary disease: characterization and risk factors.

BACKGROUND: Patients with severe chronic obstructive pulmonary disease (COPD) are at increased risk of infection by P. aeruginosa. The specific role of bronchiectasis in both infection and chronic colonization by this microorganism in COPD, however, remains ill defined.To evaluate the prevalence and risk factors for P. aeruginosa recovery from sputum in outpatients with severe COPD, characterizing P. aeruginosa isolates by pulsed-field gel electrophoresis (PFGE) and focusing on the influence of bronchiectasis on chronic colonization in these patients. METHODS: A case-cohort study of 118 patients with severe COPD attended at a Respiratory Day Unit for an acute infectious exacerbation and followed up over one year. High-resolution CT scans were performed during stability for bronchiectasis assessment and sputum cultures were obtained during exacerbation and stability in all patients. P. aeruginosa isolates were genotyped by PFGE. Determinants of the recovery of P. aeruginosa in sputum and chronic colonization by this microorganism were assessed by multivariate analysis. RESULTS: P. aeruginosa was isolated from 41 of the 118 patients studied (34.7%). Five of these 41 patients (12.2%) with P. aeruginosa recovery fulfilled criteria for chronic colonization. In the multivariate analysis, the extent of bronchiectasis (OR 9.8, 95% CI: 1.7 to 54.8) and the number of antibiotic courses (OR 1.7, 95% CI: 1.1 to 2.5) were independently associated with an increased risk of P. aeruginosa isolation. Chronic colonization was unrelated to the presence of bronchiectasis (p=0.75). In patients with chronic colonization the isolates of P. aeruginosa retrieved corresponded to the same clones during the follow-up, and most of the multidrug resistant isolates (19/21) were harbored by these patients. CONCLUSIONS: The main risk factors for P. aeruginosa isolation in severe COPD were the extent of bronchiectasis and exposure to antibiotics. Over 10% of these patients fulfilled criteria for chronic colonization by P. aeruginosa and showed clonal persistence, independently of the presence of bronchiectasis.

Cost-minimization analysis favours intravenous ferric carboxymaltose over ferric sucrose for the ambulatory treatment of severe iron deficiency.

OBJECTIVE: Intravenous iron is widely used to treat iron deficiency in day-care units. Ferric carboxymaltose (FCM) allows administration of larger iron doses than iron sucrose (IS) in each infusion (1000 mg vs. 200 mg). As FCM reduces the number of infusions required but is more expensive, we performed a cost-minimization analysis to compare the cost impact of the two drugs. MATERIALS AND METHODS: The number of infusions and the iron dose of 111 consecutive patients who received intravenous iron at a gastrointestinal diseases day-care unit from 8/2007 to 7/2008 were retrospectively obtained. Costs of intravenous iron drugs were obtained from the Spanish regulatory agencies. The accounting department of the Hospital determined hospital direct and indirect costs for outpatient iron infusion. Non-hospital direct costs were calculated on the basis of patient interviews. In the pharmacoeconomic model, base case mean costs per patient were calculated for administering 1000 mg of iron per infusion using FCM or 200 mg using IS. Sensitivity analysis and Monte Carlo simulation were performed. RESULTS: Under baseline assumptions, the estimated cost of iron infusion per patient and year was €304 for IS and €274 for FCM, a difference of €30 in favour of FCM. Adding non-hospital direct costs to the model increased the difference to €67 (€354 for IS vs. €287 for FCM). A Monte Carlo simulation taking into account non-hospital direct costs favoured the use of FCM in 97% of simulations. CONCLUSION: In this pharmacoeconomic analysis, FCM infusion reduced the costs of iron infusion at a gastrointestinal day-care unit.

Meta-analysis: comparative efficacy of H2-receptor antagonists and proton pump inhibitors for reducing aspiration risk during anaesthesia depending on the administration route and schedule.

H2-receptor antagonists (H2RA) and proton pump inhibitors (PPI) are widely used for aspiration prophylaxis in patients receiving general anaesthesia. Many randomized trials have compared these agents but it remains unclear which drug type is more effective in reducing the number of patients at risk of complications. The study aimed to compare their efficacy for decreasing the number of patients at risk of acid aspiration during general anaesthesia. Major databases were systematically searched. Randomized controlled trials comparing PPI and H2RA were selected. Sub-analyses were performed considering the dose, the dosing schedule, and the route of administration. Eighteen studies fulfilled the inclusion criteria. The main analysis showed a non-significant trend for H2RA being more effective than PPI. Only when both drugs were administered per os, as a single dose and immediately before surgery, was H2RA significantly more effective than PPI. By contrast, the effect of PPI and H2RA was similar when they were administered in two doses (the night before and on the morning of surgery) or when the drugs were given intravenously. A single H2RA dose before surgery is highly effective in reducing the number of patients at risk of acid aspiration. PPI administered in two oral doses or in a single intravenous infusion seems to be as effective as H2RA.

A new validation of the Spanish Work Productivity and Activity Impairment Questionnaire-Crohn's disease version.

OBJECTIVES: The Work Productivity and Activity Impairment Questionnaire (WPAI) is an instrument that measures work impairment in the setting of different diseases. One previous study validating the WPAI in Crohn's disease (CD) patients suggested that its reproducibility may be unsatisfactory. This study evaluated the validity and reproducibility of the Spain Spanish version of the WPAI questionnaire in CD patients. METHODS: In a prospective study, convergent validity was tested comparing WPAI with quality of life and CD activity indices. Known-groups validity was assessed by comparing WPAI scores in CD patients with active versus inactive disease. Reproducibility of repeated tests was evaluated by comparing two WPAI measures obtained two to four weeks apart in stable patients. RESULTS: One hundred eight patients were included in the various steps of the analysis. The WPAI showed adequate known groups validity and convergent validity. The reproducibility of the test and, specifically, that of the evaluation of presenteeism (the impairment of productivity while working) were good. CONCLUSIONS: This study confirms the validity of WPAI for measuring work impairment in CD patients. In contrast to previous studies, the test reproducibility was adequate.

Avian influenza in ovo vaccination with replication defective recombinant adenovirus in chickens: vaccine potency, antibody persistence, and maternal antibody transfer.

Protective immunity against avian influenza (AI) can be elicited in chickens in a single-dose regimen by in ovo vaccination with a replication-competent adenovirus (RCA)-free human adenovirus serotype 5 (Ad)-vector encoding the AI virus (AIV) hemagglutinin (HA). We evaluated vaccine potency, antibody persistence, transfer of maternal antibodies (MtAb), and interference between MtAb and active in ovo or mucosal immunization with RCA-free recombinant Ad expressing a codon-optimized AIV H5 HA gene from A/turkey/WI/68 (AdTW68.H5(ck)). Vaccine coverage and intrapotency test repeatability were based on anti-H5 hemagglutination inhibition (HI) antibody levels detected in in ovo vaccinated chickens. Even though egg inoculation of each replicate was performed by individuals with varying expertise and with different vaccine batches, the average vaccine coverage of three replicates was 85%. The intrapotency test repeatability, which considers both positive as well as negative values, varied between 0.69 and 0.71, indicating effective vaccination. Highly pathogenic (HP) AIV challenge of chicken groups vaccinated with increasing vaccine doses showed 90% protection in chickens receiving > or = 10(8) ifu (infectious units)/bird. The protective dose 50% (PD50) was determined to be 10(6.5) ifu. Even vaccinated chickens that did not develop detectable antibody levels were effectively protected against HP AIV challenge. This result is consistent with previous findings ofAd-vector eliciting T lymphocyte responses. Higher vaccine doses significantly reduced viral shedding as determined by AIV RNA concentration in oropharyngeal swabs. Assessment of antibody persistence showed that antibody levels of in ovo immunized chickens continued to increase until 12 wk and started to decline after 18 wk of age. Intramuscular (IM) booster vaccination with the same vaccine at 16 wk of age significantly increased the antibody responses in breeder hens, and these responses were maintained at high levels throughout the experimental period (34 wk of age). AdTW68.H5(ch)-immunized breeder hens effectively transferred MtAb to progeny chickens. The level of MtAb in the progenies was consistent with the levels detected in the breeders, i.e., intramuscularly boosted breeders transferred higher concentrations of antibodies to the offspring. Maternal antibodies declined with time in the progenies and achieved marginal levels by 34 days of age. Chickens with high maternal antibody levels that were vaccinated either in ovo or via mucosal routes (ocular or spray) did not seroconvert. In contrast, chickens without MtAb successfully developed specific antibody levels after either in ovo or mucosal vaccination. These results indicate that high levels of MtAb interfered with active Ad-vectored vaccination.