Multiplex PCR in the empirical antibiotic treatment of patients with SARS-CoV-2 and bacterial respiratory superinfection.

Background: The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic led to overuse of antimicrobials, which increased concerns regarding antimicrobial resistance. Objective: To measure the impact of a multiplex polymerase chain reaction (PCR) pneumonia panel on empirical antibiotic treatment for patients with critical coronavirus disease 2019 (COVID-19) with suspected bacterial respiratory superinfection. Methods: This descriptive, prospective study was undertaken in a 36-bed intensive care unit from June 2020 to July 2021. Patients with severe COVID-19 who were ventilated and under suspicion of bacterial respiratory superinfection were included in the study. The intervention was a semi-quantitative multiplex PCR alongside concurrent standard cultures. When PCR panel results were expected to be obtained within 3 h of sampling, empirical antibiotic treatment was not administered while awaiting the results. Otherwise, empirical treatment was initiated. Patients classified as 'avoided empirical treatment' avoided 48-72 h of empirical antibiotic therapy. For those patients who received empirical treatment, the PCR panel results were used to decide whether treatment should be escalated, de-escalated, maintained or stopped. Positive and negative predictive values, and 'avoided empirical treatment' were calculated. Medical conduct and panel results were analysed for patients who received empirical treatment. Results: Eighty-two patients (71% male, 29% female) were included in this study. The mean age was 57.5 years, and the mean APACHE II score was 16. Ninety PCR panels were performed, and the negative and positive predictive values were 99.9% and 66.7%, respectively. Empirical treatment was avoided in 61% of episodes. Of those patients who were receiving antibiotics when the PCR panel was performed, treatment was de-escalated in 71%, escalated in 14%, stopped in 9% and maintained in 6%. A diagnosis of bacterial respiratory superinfection was ruled out in 19% of cases. Conclusions: PCR panels prevented the initiation of empirical antibiotic treatment in two-thirds of patients, and led to de-escalation in more than two-thirds of those who had started empirical antibiotic treatment. The high negative predictive value of the PCR panel allowed the diagnosis of bacterial respiratory superinfection to be ruled out. This tool represents a significant contribution to diagnostic stewardship in order to avoid the unnecessary use of antibiotics.

Hospital environment hygiene nurse: a key player to reduce healthcare associated infections by multi-resistant organisms.

BACKGROUND: Multi-Resistant Organisms (MRO) healthcare-associated infections (HAI) are closely associated with contamination of surfaces. Outsourced companies are usually in charge of both hospital hygiene and environmental hygiene personnel (EHP) supervision, which can result in bias. METHODS: A quasi-experimental study. The intervention was to add the "Hospital Environment Hygiene Nurse" (HEHN). MRO acquired infection rate and MRO acquired colonized rate were calculated, pre and post intervention. Confounding variables: MRO carriage rate upon admission and hospitalisation days median (HDM) were calculated. RESULTS: Median length of stay: 5 days (p=0.85, interquartile range=6 days). Carriage rate upon admission: 4.3% for pre-intervention vs 5.3% post-intervention, dif. (CI 95%): 1% (-1% to 2.9%) p=0.33. MRO acquired infection rate: 4.3% for pre-intervention vs. 2% post-intervention, Standardized Infection Ratio (SIR) (CI 95%): 0.47 (0.25 to 0.87). MRO acquired colonization rate:10.4% for pre-intervention vs. 7.9% post-intervention, SIR (CI 95%): 0.75 (0.53 to 1.07). CONCLUSIONS: As a reinforcement to standard infection control (IC) measures in place, the incorporation of an exclusive, full-time HEHN was significantly useful to reduce MRO HAI.

Symposium review: The influences of heat stress on bovine mammary gland function.

Heat stress reduces cow milk yield and results in a significant economic loss for the dairy industry. During lactation, heat stress lowers milk production by 25 to 40% with half of the decrease in milk synthesis resulting from the reduced feed intake. In vitro studies indicate that primary bovine mammary epithelial cells display greater rates of programmed cell death when exposed to high ambient temperatures, which may lead to a decrease in the total number of mammary epithelial cells in the mammary gland, partially explaining the lower milk production of lactating cows under heat stress. The function of mammary cells is also altered by heat stress. In response to heat stress, mammary cells display higher gene expression of heat shock proteins, indicating a need for cytoprotection from protein aggregation and degradation. Further, heat stress results in increased gene expression without altering protein expression of mammary epithelial cell junction proteins, and does not substantially influence the integrity of mammary epithelium. These data suggest that the mammary gland strives to maintain cell-to-cell junction integrity by synthesizing more proteins to compensate for protein losses induced by heat stress. During the dry period, heat stress negatively affects mammary gland development by reducing mammary cell proliferation before parturition, resulting in a dramatic decrease in milk production in the subsequent lactation. In addition to mammary growth, the mammary gland of the heat-stressed dry cow has reduced protein expression of autophagic proteins in the early dry period, suggesting heat stress influences mammary involution. Emerging evidence also indicates that heifers born to cows that experience late-gestation heat stress have lower milk yield during their first lactation, implying that the maternal environment may alter mammary gland development of the offspring. It is not clear if this is due to a direct epigenetic modification of prenatal mammary gland development by maternal heat stress. More research is needed to elucidate the effect of heat stress on mammary gland development and function.

Effects of heat stress and dietary zinc source on performance and mammary epithelial integrity of lactating dairy cows.

Dietary Zn and heat stress alter gut integrity in monogastric animals. However, effects of Zn on mammary epithelial integrity in heat-stressed lactating dairy cows have not been studied. Multiparous lactating Holstein cows (n = 72) were randomly assigned to 1 of 4 treatments with a 2 × 2 factorial arrangement to study the effects of environment and Zn source on performance and mammary epithelial integrity. Treatments included 2 environments [cooled (CL) or not cooled (NC)] and 2 Zn sources [75 mg/kg of supplemental Zn as Zn hydroxychloride (IOZ) or 35 mg/kg of Zn hydroxychloride + 40 mg/kg of Zn-Met complex (ZMC)]. The experiment was divided into baseline and environmental challenge phases of 84 d each. All cows were cooled during the baseline phase (temperature-humidity index = 72.5), whereas NC cows were not cooled during environmental challenge (temperature-humidity index = 77.7). Mammary biopsies were collected on d 7 and 56 relative to the onset of environmental challenge to analyze gene expression of claudin 1, 4, and 8, zonula occludens 1, 2, and 3, occludin, and E-cadherin and protein expression of occludin and E-cadherin. Deprivation of cooling increased respiration rate (64.8 vs. 73.9 breaths/min) and vaginal temperature (39.03 vs. 39.94°C) and decreased dry matter intake (26.7 vs. 21.6 kg/d). Energy-corrected milk yield decreased for NC cows relative to CL cows (24.5 vs. 34.1 kg/d). An interaction between environment and Zn source occurred for milk fat content as CL cows fed ZMC had lower milk fat percentage than other groups. Relative to CL cows, NC cows had lower concentrations of lactose (4.69 vs. 4.56%) and solids-not-fat (8.46 vs. 8.32%) but a higher concentration of milk urea nitrogen (9.07 vs. 11.02 mg/mL). Compared with IOZ, cows fed ZMC had lower plasma lactose concentration during baseline and tended to have lower plasma lactose concentration during environmental challenge. Plasma lactose concentration tended to increase at 3, 5, and 41 d after the onset of environmental challenge in NC cows relative to CL cows. Treatment had no effect on milk BSA concentration. Cows fed ZMC tended to have higher gene expression of E-cadherin relative to IOZ. Compared with CL, NC cows had increased gene expression of occludin and E-cadherin and tended to have increased claudin 1 and zonula occludens 1 and 2 gene expression in the mammary gland. Protein expression of occludin and E-cadherin was unchanged. In conclusion, removing active cooling impairs lactation performance and affects gene expression of proteins involved in the mammary epithelial barrier, and feeding a portion of dietary zinc as ZMC improves the integrity of the mammary epithelium.

Influence of follicle stage on artificial ovary outcome using fibrin as a matrix.

STUDY QUESTION: Do primordial-primary versus secondary follicles embedded inside a fibrin matrix have different capabilities to survive and grow after isolation and transplantation? SUMMARY ANSWER: Mouse primordial-primary follicles showed a lower recovery rate than secondary follicles, but both were able to grow. WHAT IS KNOWN ALREADY: Fresh isolated mouse follicles and ovarian stromal cells embedded in a fibrin matrix are capable of surviving and developing after short-term autografting. STUDY DESIGN, SIZE, DURATION: In vivo experimental model using 11 donor Naval Medical Research Institute (NMRI) mice and 11 recipient severe combined immunodeficiency (SCID) mice. Both ovaries from all NMRI mice were mechanically disrupted and primordial-primary and secondary follicles were isolated with ovarian stromal cells. They were then encapsulated in a fibrin matrix composed of 12.5 mg/ml of fibrinogen (F12.5) and 1 IU/ml of thrombin (T1) (F12.5/T1), and grafted to the inner part of the peritoneum of SCID mice for 2 and 7 days. PARTICIPANTS/MATERIALS, SETTING, METHODS: This study was conducted at the Gynecology Research Unit, Université Catholique de Louvain. All materials were used to conduct histological (H-E staining) and immunohistochemical (Ki67, TUNEL) analyses. MAIN RESULTS AND THE ROLE OF CHANCE: Although all grafted fibrin clots were recovered, the follicle recovery rate on day 2 was 16 and 40% for primordial-primary and secondary follicles respectively, while on day 7, it was 6 and 28%. The secondary group showed a significantly higher recovery rate than the primordial-primary group (23%, P-value <0.001). Follicles found in both groups were viable, as demonstrated by live/dead assays, and no difference was observed in the apoptosis rate between groups, as evidenced by TUNEL. Their growth to further stages was confirmed by Ki67 immunostaining. LIMITATIONS, REASONS FOR CAUTION: As demonstrated by our results, secondary follicles appear to be more likely to survive and develop than primordial-primary follicles in a fibrin matrix after both periods of grafting. These findings may also be attributed to the specific features of the fibrin matrix, which could benefit larger follicles, but not smaller follicles. WIDER IMPLICATIONS OF THE FINDINGS: This study is essential to understanding possible impairment caused by factors such as the isolation procedure or fibrin matrix composition to the survival and development of different follicle stages. It therefore provides the basis for further investigations with longer periods of grafting. STUDY FUNDING/COMPETING INTERESTS: This study was supported by grants from the Fonds National de la Recherche Scientifique de Belgique (grant Télévie No. 7.4578.14 and 7.4627.13, grant 5/4/150/5 awarded to Marie-Madeleine Dolmans), Fonds Spéciaux de Recherche, Fondation St Luc, the Foundation Against Cancer, and the Region Wallone (Convention N°6519-OVART) and donations from Mr Pietro Ferrero, Baron Frère and Viscount Philippe de Spoelberch. None of the authors have any competing interests to declare.

Schwannomas, benign tumors with a senescent phenotype.

BACKGROUND: Schwannomas are benign nerve sheath tumors that only very rarely undergo malignant changes. Oncogenic-induced senescence is a defense mechanism against such malignant transformation. Different molecular pathways are involved in this process, such as RAS-RAF-MAPK. Based on the fact that the RAS-RAF-MAPK pathway is known to be activated in peripheral nerve sheath tumors, this study analyzes senescence markers in Schwannomas to demonstrate the possible role of senescence in their genesis. METHODS: A retrospective immunohistochemical study was done in 39 schwannoma and 18 malignant peripheral nerve sheath tumors (MPNST). Staining for p16INK4a, Ki67, p53 and CyclinD1 was performed in all the cases. Additionally, ß-galactosidase staining was done in those cases in which frozen tissue was available (n=8). RESULTS: Higher levels of p16INK4a (p=0.0001) and lower levels of Ki67 (p=0.0001) were found in Schwannomas. Beta-galactosidase activity was positive in 5/5 Schwannomas and negative in 3/3 MPNST. CONCLUSIONS: Our results support the senescence nature of Schwannomas and the absence of a senescence phenotype in MPNST.

TIME INVARIANT MULTI ELECTRODE AVERAGING FOR BIOMEDICAL SIGNALS.

One of the biggest challenges in averaging ECG or EEG signals is to overcome temporal misalignments and distortions, due to uncertain timing or complex non-stationary dynamics. Standard methods average individual leads over a collection of epochs on a time-sample by time-sample basis, even when multi-electrode signals are available. Here we propose a method that averages multi electrode recordings simultaneously by using spatial patterns and without relying on time or frequency.

Triennial Growth Symposium: leucine acts as a nutrient signal to stimulate protein synthesis in neonatal pigs.

The postprandial increases in AA and insulin independently stimulate protein synthesis in skeletal muscle of piglets. Leucine is an important mediator of the response to AA. We have shown that the postprandial increase in leucine, but not isoleucine or valine, acutely stimulates muscle protein synthesis in piglets. Leucine increases muscle protein synthesis by modulating the activation of mammalian target of rapamycin (mTOR) complex 1 and signaling components of translation initiation. Leucine increases the phosphorylation of mTOR, 70-kDa ribosomal protein S6 kinase-1, eukaryotic initiation factor (eIF) 4E-binding protein-1, and eIF4G; decreases eIF2α phosphorylation; and increases the association of eIF4E with eIF4G. However, leucine does not affect the upstream activators of mTOR, that is, protein kinase B, adenosine monophosphate-activated protein kinase, and tuberous sclerosis complex 1/2, or the activation of translation elongation regulator, eukaryotic elongation factor 2. The action of leucine can be replicated by α-ketoisocaproate but not by norleucine. Interference by rapamycin with the raptor-mTOR interaction blocks leucine-induced muscle protein synthesis. The acute leucine-induced stimulation of muscle protein synthesis is not maintained for prolonged periods, despite continued activation of mTOR signaling, because circulating AA fall as they are utilized for protein synthesis. However, when circulating AA concentrations are maintained, the leucine-induced stimulation of muscle protein synthesis is maintained for prolonged periods. Thus, leucine acts as a nutrient signal to stimulate translation initiation, but whether this translates into a prolonged increase in protein synthesis depends on the sustained availability of all AA.

Amino acids and insulin are regulators of muscle protein synthesis in neonatal pigs.

The stage of development between birth and weaning in mammals is a period of very rapid growth that is crucial for the long-term well-being of the animal. The rate of protein deposition in neonatal animals is very high because dietary protein is efficiently utilized to increase body protein mass. Our studies in neonatal pigs have shown that this high efficiency of protein deposition is largely due to the marked increase in protein synthesis after feeding, and this response is particularly profound in the skeletal muscle. The enhanced stimulation of muscle protein synthesis in neonates after feeding is independently mediated by the rise in insulin and amino acids and this response declines with age. Intracellular signaling components that respond to the postprandial rise in amino acids and insulin have been identified and their activation has been shown to be elevated in skeletal muscle of neonatal pigs after a meal and to decrease with development. The enhanced activation of these components in the amino acid and insulin signaling pathways in neonatal muscle contributes to the high rate of muscle protein synthesis and rapid gain in skeletal muscle mass in newborn pigs, which are essential determinants of efficient growth during development.

Obstrucción de arteria central de la retina: casos clínicos y controversias respecto a su manejo / Central retinal artery occlusion: clinical cases

Se presentan 3 casos clínicos de obstrucción de arteria central de la retina del ojo izquierdo: Una paciente con patología cardiovascular concomitante, sin posibilidad de fibrinolisis selectiva, con antecedentes de amaurosis fugax y secuelas neurológicas por episodios previos de tromboembolismo a territorio superior no detectados, y 2 pacientes que consultaron tardíamente en los cuales no se efectuó ningún tratamiento, sólo búsqueda del origen del cuadro ocular, en forma ambulatoria. Se discute acerca del tratamiento actual de las obstrucciones arteriales retinales agudas y la controversia referente a los ensayos clínicos en curso.

We present three clinical cases about central retinal artery occlusion all in the left eye: A female patient with concomitant cardiovascular disease, without chance selective fibrinolysis, who suffered amaurosis fugax and neurologic consequences from undetectable previous events of thromboembolism upward central nervous system, and two male patients with late consultation which no treatment was applied, only seeking origin of the ocular disease, by n outpatient basis. We discuss about current treatment of acute central retinal artery occlusion and controversy referring to ongoing clinical trials.

Crecimiento, supervivencia y herbivoría de plántulas de Brosimum alicastrum (Moraceae), una especie del sotobosque neotropical

Growth, survival and herbivory of seedlings in Brosimum alicastrum (Moraceae), a species from the Neotropical undergrowth. Growth responses, survival, and herbivory, on seedlings of Brosimum alicastrum were studied in a neotropical Mexican forest. We selected 122 seedlings and divided them into three groups assigned to defoliation treatments: control or 0 (n=21), 50 (n=51) and 90% (n=50). Every 4 months during two years we measured seedling growth (in terms of relative growth rate in biomass, leaf area growth, produced leaves and height growth) and survival. In addition, we evaluated every 12 months pathogen damage and insect herbivory using a 2 mm-2 grid. Separately, we estimated mammal herbivory in 3-month old seedlings that were selected within a plot of 500 m x 10 m (N=1095). Pathogen damage and insect herbivory were evaluated within the same plot in 113 seedlings. We found that 50 % defoliated seedlings showed compensatory responses in all growth parameters. Relative growth rate and height growth also had a compensatory response in seedlings at 90% defoliation. Relative growth rate and leaf area growth gradually decreased with time although height growth seedling showed an opposite pattern. Leaves produced were not affected by time. Estimated seedling survival probability increased with defoliation to a maximum of 97%, decreasing at 24 month to 37%. Mammal herbivory was more frequent and severe than herbivory caused by pathogens and insects. In some cases, mammal herbivory produced total defoliation. Compensatory growth in leaf area growth, produced leaves and height growth seedling suggest a synergic compensatory mechanism expressed in a whole-plant growth biomass (relative growth rate). Compensation and survival results suggest trade-offs at the leaf level, such as leaf area growth and produced leaves versus chemical defenses, respectively. Rev. Biol. Trop. 56 (4): 2055-2067. Epub 2008 December 12.

Se estudiaron las respuestas de crecimiento, supervivencia y los diferentes tipos de herbivoría sobre plántulas de B. alicastrum en una selva neotropical de México. Se seleccionaron 122 plántulas de una población las cuales se asignaron a tres tratamientos de defoliación: control o 0% (n=21), 50% (n=51) y 90% (n=50). Cada 4 meses durante dos años se midió su crecimiento (en términos de la tasa relativa de crecimiento en biomasa, área foliar, hojas producidas y altura) y supervivencia. Además cada 12 meses, mediante el uso de una cuadricula de 2mm-2, se evaluó la herbivoría causada por patógenos e insectos. También dentro de una parcela de 500 m largo x 10 m de ancho se evaluó en 1095 plántulas de 3 meses de edad la herbivoría por mamíferos. En la misma parcela pero en 113 plántulas se estimó la herbivoría por patógenos e insectos. Las plántulas defoliadas al 50% compensaron su crecimiento en todas las estructuras medidas, pero sólo la tasa relativa de crecimiento y altura lo hicieron con la defoliación al 90%. La tasa relativa de crecimiento y el área foliar disminuyeron gradualmente con el tiempo, contrario a la altura con un patrón opuesto. El número de hojas producidas no se afectó por el tiempo. La probabilidad estimada de supervivencia incrementó hasta un 95% con la defoliación y disminuyó hasta un 37% a los 24 meses. La herbivoría por mamíferos fue el más incidente y severo, en algunos casos hasta un 100% de defoliación. En tanto la causada por patógenos e insectos fue secundaria. El crecimiento compensatorio en área foliar, producción de hojas y altura sugieren un mecanismo compensatorio sinérgico expresado a nivel del crecimiento individual de la planta (tasa de crecimiento en biomasa). Al mismo tiempo junto con la supervivencia sugiere un posible compromiso entre las respuestas de crecimiento a nivel de la hoja - área foliar y hojas producidas - versus producción de defensas químicas.

Incidentalomas en patología del tiroides / Frecuency and characteristics of thyroid incidentalomas

Introducción: La realización de la Ultrasonografía de alta resolución ha hecho posible la detección de pequeños nodulos tiroideos asintomáticos. El incidentaloma tiroideo con una frecuencia entre el 1,5 al 10 por ciento, ha originado el dilema de cómo deben ser tratados1,2. Objetivos: Determinar su incidencia, las características clínicas y ultrasonográficas, así como el manejo más apropiado cuando se detectan incidentalmente nodulos tiroideos benignos o malignos igual o menores de 1,0 cm. Material y Método: Se realizó la revisión retrospectiva de las historias clínicas en 817 pacientes tratados por patología tiroidea entre 1984 y 2007. Resultados: La prevalencia del incidentaloma tiroideo fue del 8,44 por ciento. El porcentaje de malignidad fue del 27,54 por ciento. Entre los incidentalomas tiroideos benignos o malignos, no se encontraron diferencias significativas en relación con la edad, número, tamaño, y en las pruebas de función tiroidea, o gammagrafía con Tc99. Las características al ultrasonido de ecoestructura sólida, márgenes irregulares, o presencia de calcificaciones resultaron significativas en la detección de incidentalomas tiroideos malignos (p < 0,05). Conclusiones: No se evidenciaron diferencias significativas en los parámetros clínicos y de laboratorio entre los nodulos tiroideos benignos o malignos menores de 1,0 cm; sin embargo, los hallazgos reportados al ultrasonido pueden servir de base en la elección de la mejor decisión en cuanto a las estrategias a seguir para su óptima conducción.

Background: High-resolution ultrasonography deteets asymptomatic small thyroid nodules. These so called thyroid incidentalomas have created a clinical dilemma about their proper management. Aim: To report the incidence, clinical features and management of thyroid nodules of less than 1 cm diameter, detected incidentally on ultrasound. Material and Methods: Retrospective review of medical records of 817 patients admitted to a surgical ward for the management of a thyroid nodule. The frequency, and characteristics of incidentalomas, defined as nodules of less than 1,5 cm diameter detected incidentally, was studied. Results: Sixty nine patients (8,4 percent) had an incidentaloma. Of these 19 (27 percent) were malignant. There were no significant differences in age, nodule size and number, thyroid function tests, and Tc99 thyroid scans between benign and malignant incidentalomas. On ultrasound examination, a solid echo-structure, irregular margins, and the presence of calcifications were more common in malignant incidentalomas (p < 0,05). Conclusions: In this series, 8 percent of patients had an incidentaloma and the frequency of malignaney among these lesions was 27 percent. Ultrasound examination can be useful to differentiate between benign and malignant nodules.

Endoteliopatía corneal autoinmune como manifestación de uveitis intermedia / Corneal autoimmune endotheliopathy as manifestation of intermediate uveitis in children

Background: Intermediate Uveitis (IU) is an important cause of uveitis in children. It is considered a chronic intraocular inflammation that mainly affects the anterior vitreous and peripheral retina. Pars Planitis is a subtype of IU, consisting of a white opacity that covers the pars plana and ora serrata plus vitreous condensations in the eye. Corneal endothelium disease is a rare clinical finding associated with pars planitis. Objective: Describe the corneal manifestations in IU and its associated treatment between ophthalmology and pediatric rheumatology. Case-report: A 5 years-old boy with autoimmune endotheliopathy and unilateral pars planitis in the right eye. Initially, he was treated topically, but evolved with intraocular complications that required systemic medication. Long-term follow-up was performed, searching for associated systemic diseases, until one of these entities appeared. Conclusion: It is very important to search for inflammation in the anterior vitreous and pars plana in all children with corneal endotheliopathy, considering that an early and integral management of IU could diminish the risk of visual impairment as a complication.

Introducción: La Uveitis Intermedia (UI) es una causa importante de uveitis infantil. Se considera como una inflamación intraocular crónica que afecta principalmente a la retina periférica y vitreo anterior. La Pars Planitis es un subtipo de UI caracterizada por opacidades blanquecinas sobre la pars plana y ora serrata más condensaciones vitreas. La enfermedad del endotelio corneal es un hallazgo clínico infrecuente asociado con la Pars Planitis. Objetivo: Destacar la manifestación corneal de una UI y el tratamiento de la enfermedad entre oftalmólogo y reumatólogo infantil. Caso clínico: Se presenta caso clínico de niño de 5 años de edad con endoteliopatía autoinmune asociada a Pars Planitis unilateral del ojo derecho, que en principio se trató localmente, pero evolucionó con complicaciones intraoculares que requirieron medicación sistémica y se efectuó un seguimiento clínico por varios años buscando enfermedades sistémicas asociadas a UI hasta que ella apareció. Conclusión: Es necesario buscar la presencia de inflamación de pars plana y vitreo en todo niño que se presente con endoteliopatía corneal, considerando que el tratamiento oportuno y manejo integral del paciente con UI puede disminuir el riesgo de pérdida visual asociado a las complicaciones de esta enfermedad.

[Growth, survival and herbivory of seedlings in Brosimum alicastrum (Moraceae), a species from the Neotropical undergrowth]. / Crecimiento, supervivencia y herbivoría de plántulas de Brosimum alicastrum (Moraceae), una especie del sotobosque neotropical.

Growth responses, survival, and herbivory, on seedlings of Brosimum alicastrum were studied in a neotropical Mexican forest. We selected 122 seedlings and divided them into three groups assigned to defoliation treatments: control or 0 (n=21), 50 (n=51) and 90% (n=50). Every 4 months during two years we measured seedling growth (in terms of relative growth rate in biomass, leaf area growth, produced leaves and height growth) and survival. In addition, we evaluated every 12 months pathogen damage and insect herbivory using a 2 mm(-2) grid. Separately, we estimated mammal herbivory in 3-month old seedlings that were selected within a plot of 500 m x 10 m (N=1095). Pathogen damage and insect herbivory were evaluated within the same plot in 113 seedlings. We found that 50% defoliated seedlings showed compensatory responses in all growth parameters. Relative growth rate and height growth also had a compensatory response in seedlings at 90% defoliation. Relative growth rate and leaf area growth gradually decreased with time although height growth seedling showed an opposite pattern. Leaves produced were not affected by time. Estimated seedling survival probability increased with defoliation to a maximum of 97%, decreasing at 24 month to 37%. Mammal herbivory was more frequent and severe than herbivory caused by pathogens and insects. In some cases, mammal herbivory produced total defoliation. Compensatory growth in leaf area growth, produced leaves and height growth seedling suggest a synergic compensatory mechanism expressed in a whole-plant growth biomass (relative growth rate). Compensation and survival results suggest trade-offs at the leaf level, such as leaf area growth and produced leaves versus chemical defenses, respectively.

Postnatal ontogeny of skeletal muscle protein synthesis in pigs.

The neonatal period is characterized by rapid growth and elevated rates of synthesis and accretion of skeletal muscle proteins. The fractional rate of muscle protein synthesis is very high at birth and declines rapidly with age. The elevated capacity for muscle protein synthesis in the neonatal pig is driven by the high ribosome content and, together with an increased efficiency of the translation process, promotes accelerated protein synthesis rates. Feeding profoundly stimulates muscle protein synthesis in neonatal pigs and the response decreases with age. The feeding-induced stimulation of muscle protein synthesis is modulated by an enhanced sensitivity to the postprandial increase in insulin and amino acids. The developmental decline in the response to insulin and amino acids parallels a marked decrease in the feeding-induced activation of translation initiation factors that regulate the binding of mRNA to the 40S ribosomal complex. The abundance and activation of many known positive regulators of the nutrient- and insulin-signaling pathways that are involved in translation initiation are high, whereas those of many negative regulators are low in skeletal muscle of younger pigs. Thus, the activation and(or) abundance of the positive regulators, such as the insulin receptor, insulin receptor-substrate-1, phosphoinositide-3 kinase, phosphoinositide-dependent kinase-1, protein kinase B, mammalian target of rapamycin, raptor, ribosomal protein S6 kinase-1, eukaryotic initiation factor (eIF) 4E-binding protein 1, and eIF4E associated with eIF4G, are greater in 7-d-old pigs than in 26-d-old pigs. The activation of negative regulators, including protein tyrosine phosphatase-1B, phosphatase and tensin homologue deleted on chromosome 10, protein phosphatase 2A, and tuberous sclerosis complex 1/2, are lower in 7-d-old pigs than in 26-d-old pigs. Thus, the developmental decline in the stimulation of skeletal muscle protein synthesis by insulin and amino acids is due in part to the developmentally related decrease in the activation of the signaling pathways that lead to translation initiation.

Resistencia a la terapia antirretroviral en pacientes infectados con el virus VIH-1 en Chile 2002-2005 / Resistance to anti-retroviral therapy in Chilean patients with HIV-1 from 2002 to 2005

Background: Resistance limits the effectiveness of anti-retroviral therapy. In Chile, there is free access to highly active anti-retroviral therapy since 2001, but there is no information about the frequency of mutations associated to drug resistance. Aim: To determine the most common mutations associated to anti-retroviral drug resistance in Chile. Materials and Methods: Retrospective study of 710 genotype analysis coming from 568 patients aged 22 to 70 years (85 percent males) with virological failure. The analysis was performed using a commercially available sequencing kit (Trugene HIV-1 genotypic assay from Bayer S.A). Results: Mean CD4+ cell count and viral load were 154 cells/fil and 228784 RNA copies/ml, respectively. The frequency of resistance to nucleoside RT inhibitors (NRTI), non nucleoside RT inhibitors (NNRTI) and protease inhibitors (PI) was 71 percent, 62 percent and 22 percent, respectively. The most common mutations found were T215Y (46 percent), L10F (44 percent), Ml84V (3896), K103N (35 percent) and M41L (32 percent). Fifty five percent of mutations corresponded to the TAM (thymidine analogue mutations) group. Multiresistance was 47 percent to NNRTI, 7 percent to NRTI, 4 percent to PI and 0.7 percent to all groups. During the four years of the study, there was a significant increase in NNRTI resistance. Conclusions: These data provides important information about the epidemiology of drug resistance mutations and should help to design newHAARTstrategies.

[Resistance to anti-retroviral therapy in Chilean patients with HIV-1 from 2002 to 2005]. / Resistencia a la terapia antirretroviral en pacientes infectados con el virus VIH-1 en Chile 2002-2005.

BACKGROUND: Resistance limits the effectiveness of anti-retroviral therapy. In Chile, there is free access to highly active anti-retroviral therapy since 2001, but there is no information about the frequency of mutations associated to drug resistance. AIM: To determine the most common mutations associated to anti-retroviral drug resistance in Chile. MATERIALS AND METHODS: Retrospective study of 710 genotype analysis coming from 568 patients aged 22 to 70 years (85% males) with virological failure. The analysis was performed using a commercially available sequencing kit (Trugene HIV-1 genotypic assay from Bayer S.A). RESULTS: Mean CD4(+) cell count and viral load were 154 cells/microl and 228784 RNA copies/ml, respectively. The frequency of resistance to nucleoside RT inhibitors (NRTI), non nucleoside RT inhibitors (NNRTI) and protease inhibitors (PI) was 71 %, 62% and 22%, respectively. The most common mutations found were T215Y (46%), L10F (44%), Ml84V (3896), K103N (35%) and M41L (32%). Fifty five percent of mutations corresponded to the TAM (thymidine analogue mutations) group. Multiresistance was 47% to NNRTI, 7% to NRTI, 4% to PI and 0.7% to all groups. During the four years of the study, there was a significant increase in NNRTI resistance. CONCLUSIONS: These data provides important information about the epidemiology of drug resistance mutations and should help to design new HAART strategies.

Nefritis intersticial granulomatosa crónica por alopurinol / Allopurinol-induced chronic granulomatous interstitial nephritis

La nefritis intersticial por fármacos es una causa relativamente frecuente de afectación renal, sin embargo el hallazgo de granulomas es excepcional. La existencia de una nefritis intersticial granulomatosa crónica por alopurinol es un hecho raramente descrito, habiéndose comunicado solamente tres casos con anterioridad. Describimos el caso de un paciente que presentó una nefritis intersticial granulomatosa tras 10 años de tratamiento con alopurinol (300 mg/día). En el momento del diagnóstico presentaba insuficiencia renal requiriendo tratamiento dialítico. Tras retirar el fármaco y recibiendo tratamiento con corticoides presentó una lenta mejoría de la función renal, permitiendo suspender la diálisis a los dos meses. A los 32 meses de seguimiento mantiene una función renal estable con un aclaramiento de creatinina de 23 ml/minuto. Discutimos el diagnóstico diferencial de las nefritis intersticiales granulomatosas así como la excepcional asociación con el tratamiento con alopurinol

Although drug induced interstitial nephritis is a relatively common cause of renal failure, granulomatous forms remain a rare condition. The development of a chronic granulomatous interstitial nephritis due to allopurinol is exceptional, only three cases have been described previously. We report on a patient who presented a granulomatous interstitial nephritis after 10 years of allopurinol administration (300 mg/day). At diagnosis, he had end stage renal disease and dialysis treatment was needed. Two months after drug withdrawal and on corticoid treatment a slow recovery of renal function was observed, allowing the interruption of dialysis. Two years after, the creatinine clearance is 23 ml/min, being dialysis free. We discuss the differential diagnosis of granulomatous interstitial nephritis and its rare association with allopurinol treatment