Bacteria associated with apical periodontitis promotes in vitro the differentiation of macrophages to osteoclasts.

OBJECTIVE: To analyze the possible in vitro effect of the cytokine RANKL and bacteria involved in apical periodontitis on the differentiation of macrophages into osteoclasts. MATERIAL AND METHODS: Bacteria were isolated (mainly E. faecium and E. faecalis) from the root canal of fifty patients with apical periodontitis, the possible effect of these bacteria on the phagocytic activity of the monocyte cell line THP-1 was analyzed by flow cytometry. Furthermore, the effect of these bacteria (alone or in combination with the cytokine RANKL) on the differentiation of THP-1 macrophages into osteoclasts was analyzed through the expression of the receptor RANK and the tartrate-resistant acid phosphatase TRAP. Finally, the release of different cytokines (IL-1ß, TNF-α, IL-6, IL-8, IL-10, and IL-12p70) by THP-1 cells induced to differentiate into osteoclasts was also analyzed. RESULTS: We observed a significant proportion of THP-1 cells were able to internalize E. faecium and E. faecalis. Furthermore, these bacteria were able to induce (alone or in combination with RANKL) a significant expression of RANK by THP-1 macrophages; accordingly, E. faecium and E. faecalis induced very significant levels of TRAP in these cells. Finally, during the differentiation of THP-1 macrophages induced by RANKL or bacteria, a significant release of the pro-inflammatory cytokines IL-6 and TNF-α was observed. CONCLUSIONS AND CLINICAL RELEVANCE: Our data suggest that the causative agents of apical periodontitis can induce the differentiation of osteoclasts as well as the release of pro-inflammatory cytokines, phenomena that may have an important role in the bone damage observed in this condition.

Pediatric perianal Crohn's disease behavior in the era of biologic therapy. / Comportamiento de la afectación perianal en pacientes pediátricos con enfermedad de Crohn en la era de la terapia biológica.

AIM OF THE STUDY: To describe perianal Crohn's disease behavior and the role of biological therapy in a sample of pediatric patients. METHODS: A retrospective study of pediatric patients with Crohn's disease (CD) treated in our institution from 2017 to 2021, with a minimum follow up period of 6 months, was conducted. Patients were divided whether they had perianal disease (PD) or not. Baseline characteristics, extension of disease, growth failure rate, aggressive pattern rate, use of biological therapy and need for surgery, among other variables, were compared between both groups. Clinical and/or radiological improvement in the last 6 months of follow up was considered good control of PD. RESULTS: Seventy eight pediatric patients with CD were included. Median age at diagnosis was 10.5 years, and median follow up time was 3.8 years. 64.1% patients were male. Of all, 15 (19.2%) had perianal disease, of which 10 had fistulizing findings and 5 had non fistulizing findings. PD was presented at diagnosis in 8 patients, and the rest developed it in a median time of 1 year from diagnosis. PD was associated with growth failure (p = 0.003), use of biological therapies (p = 0.005), and need for second line of biologics (p = 0.005). Most patients (12/15, 80%) had good control of PD with the treatment received. CONCLUSIONS: CD patients with PD seem to need a more aggressive treatment, with biological therapies playing a key role for its handling nowadays. These patients require close nutritional evaluation that ensures proper development and growth.

OBJETIVO DEL ESTUDIO: Describir el comportamiento de la enfermedad de Crohn perianal y el papel de la terapia biológica en una muestra de pacientes pediátricos. METODOS: Estudio retrospectivo de pacientes pediátricos con enfermedad de Crohn (EC) tratados en nuestro centro entre 2017 y 2021, con un seguimiento mínimo de seis meses. Los pacientes se dividieron en función de si tenían enfermedad perianal (EP) o no. Se compararon entre ambos grupos las características iniciales, la extensión de la enfermedad, el índice de retraso en el crecimiento, el índice de patrón agresivo, el empleo de terapia biológica y la necesidad de cirugía, entre otras variables. Se consideró un buen control de la EP una mejoría clínica o radiológica en los 6 últimos meses de seguimiento. RESULTADOS: Se incluyeron 78 pacientes pediátricos con EC. La edad mediana en el momento del diagnóstico fue de 10,5 años, y el tiempo mediano de seguimiento fue de 3,8 años. El 64,1% de los pacientes eran varones. Del total, 15 (19,2%) tenían enfermedad perianal, de los cuales 10 presentaban hallazgos fistulizantes y 5 no fistulizantes. La EP estaba presente en el momento del diagnóstico en 8 pacientes, y el resto la desarrolló en una mediana de 1 año desde el diagnóstico. La EP se asoció con retraso en el crecimiento (p = 0,003), empleo de terapias biológicas (p = 0,005) y necesidad de una segunda línea de terapia biológica (p = 0,005). La mayoría de los pacientes (12/15, 80%) tuvieron un buen control de la EP con el tratamiento recibido. CONCLUSIONES: Los pacientes de EC con EP parecen necesitar un tratamiento más agresivo, en el que las terapias biológicas desempeñan hoy en día un papel fundamental. Estos pacientes precisan de una estrecha evaluación nutricional que garantice su correcto crecimiento y desarrollo.

Variant rs4149584 (R92Q) of the TNFRSF1A gene in patients with familial multiple sclerosis.

INTRODUCTION: Genomic studies have identified numerous genetic variants associated with susceptibility to multiple sclerosis (MS); however, each one explains only a small percentage of the risk of developing the disease. These variants are located in genes involved in specific pathways, which supports the hypothesis that the risk of developing MS may be linked to alterations in these pathways, rather than in specific genes. We analyzed the role of the TNFRSF1A gene, which encodes one of the TNF-α receptors involved in a signaling pathway previously linked to autoimmune disease. METHODS: We included 138 individuals from 23 families including at least 2 members with MS, and analyzed the presence of exonic variants of TNFRSF1A through whole-exome sequencing. We also conducted a functional study to analyze the pathogenic mechanism of variant rs4149584 (-g.6442643C > G, NM_001065.4:c.362 G > A, R92Q) by plasmid transfection into human oligodendroglioma (HOG) cells, which behave like oligodendrocyte lineage cells; protein labeling was used to locate the protein within cells. We also analyzed the ability of transfected HOG cells to proliferate and differentiate into oligodendrocytes. RESULTS: Variant rs4149584 was found in 2 patients with MS (3.85%), one patient with another autoimmune disease (7.6%), and in 5 unaffected individuals (7.46%). The 2 patients with MS and variant rs4149584 were homozygous carriers and belonged to the same family, whereas the remaining individuals presented the variant in heterozygosis. The study of HOG cells transfected with the mutation showed that the protein does not reach the cell membrane, but rather accumulates in the cytoplasm, particularly in the endoplasmic reticulum and near the nucleus; this suggests that, in the cells presenting the mutation, TNFRSF1 does not act as a transmembrane protein, which may alter its signaling pathway. The study of cell proliferation and differentiation found that transfected cells continue to be able to differentiate into oligodendrocytes and are probably still capable of producing myelin, although they present a lower rate of proliferation than wild-type cells. CONCLUSIONS: Variant rs4149584 is associated with risk of developing MS. We analyzed its functional role in oligodendrocyte lineage cells and found an association with MS in homozygous carriers. However, the associated molecular alterations do not influence the differentiation into oligodendrocytes; we were therefore unable to confirm whether this variant alone is pathogenic in MS, at least in heterozygosis.

The rs1800795 single nucleotide polymorphism in the IL6 gene is not associated with primary open angle glaucoma in Mexican population.

PURPOSE: Interleukin-6 (IL-6) is a proinflammatory cytokine with pleiotropic effects which has been related to primary open angle glaucoma (POAG) due to its particular effect of protecting the retinal ganglion cells (RGc) from the apoptosis. Different single nucleotide polymorphisms (SNP) have been associated with POAG. The aim of this study was to determine whether an association between IL-6 rs1800795 (-174 G>C) SNP and a higher risk for POAG is present in western Mexican population. METHODS: One hundred and sixty-five unrelated Mexican mestizo patients with POAG and 108 control subjects were included. Genomic DNA was extracted from leukocytes and purified, followed by genotyping and amplification by polymerase chain reaction (PCR) with Taqman Biosystem probes. Allelic and genotypic diversity was evaluated between cases and control subjects. RESULTS: There was no statistically significant association between allele and genotype frequencies, neither with dominant nor recessive genetic association models (p > 0.05). CONCLUSION: Even though there is a role of IL6 in the pathophysiology of POAG, our results ruled out the association between IL-6 and the rs1800795 SNP showing not to be an index of higher risk for POAG in Mexican population.

Dosimetric impact of rectum and bladder anatomy and intrafractional prostate motion on hypofractionated prostate radiation therapy.

OBJECTIVE: The objective of this study was to evaluate the dosimetric impact on hypofractionated prostate radiation therapy of two geometric uncertainty sources: rectum and bladder filling and intrafractional prostate motion. MATERIALS AND METHODS: This prospective study included 544 images (375 pre-treatment cone-beam CT [CBCT] and 169 post-treatment CBCT) from 15 prostate adenocarcinoma patients. We recalculated the dose on each pre-treatment CBCT once the positioning errors were corrected. We also recalculated two dose distributions on each post-treatment CBCT, either using or not intrafractional motion correction. A correlation analysis was performed between CBCT-based dose and rectum and bladder filling as well as intrafraction prostate displacements. RESULTS: No significant differences were found between administered and planned rectal doses. However, we observed an increase in bladder dose due to a lower bladder filling in 66% of treatment fractions. These differences were reduced at the end of the fraction since the lower bladder volume was compensated by the filling during the treatment session. A statistically significant reduction in target volume coverage was observed in 27% of treatment sessions and was correlated with intrafractional prostate motion in sagittal plane > 4 mm. CONCLUSIONS: A better control of bladder filling is recommended to minimize the number of fractions in which the bladder volume is lower than planned. Fiducial mark tracking with a displacement threshold of 5 mm in any direction is recommended to ensure that the prescribed dose criteria are met.

Association of tyrosine hydroxylase expression in brain and tumor with increased tumor growth in sympathectomized mice.

OBJECTIVE: Lymphocytes express tyrosine hydroxylase (TH), the rate-limiting enzyme for the synthesis of dopamine, norepinephrine and epinephrine. This suggests a broader role for cathecholamines in lymphocyte function, as well as the potential secretion of catecholamines by tumors of lymphoid origin. Our aim was to evaluate the expression of Th by murine lymphoma cells in an in vivo mouse model. For this, L5178Y-R lymphoma cells were implanted in nerve-intact and sympathectomized male BALB/c mice. Relative Th gene expression in tumor and brain was determined by quantitative PCR. Body composition, tumor volume, and plasma TH1/TH2/TH17 cytokines were also evaluated as markers of tumor-host condition and anti-tumor immune response in absence of adrenergic innervation. RESULTS: We found a significant (p = 0.045) 3.3-fold decrease of Th gene expression in tumor and a non-significant (p = 0.60) 6.9-fold increase in brain after sympathectomy. Sympathectomized mice also showed a significant increase in tumor mass at days 18 (p = 0.032) and 28 (p = 0.022) and increased interscapular fat (p = 0.04). TH1/TH2 and TH17 cytokines levels in plasma from sympathectomized tumor-bearing mice were not different from control mice. CONCLUSION: The L5178Y-R lymphoma does not express Th during in vivo progression.

Effect of an individualized versus standard pneumoperitoneum pressure strategy on postoperative recovery: a randomized clinical trial in laparoscopic colorectal surgery.

BACKGROUND: It remains uncertain whether individualization of pneumoperitoneum pressures during laparoscopic surgery improves postoperative recovery. This study compared an individualized pneumoperitoneum pressure (IPP) strategy with a standard pneumoperitoneum pressure (SPP) strategy with respect to postoperative recovery after laparoscopic colorectal surgery. METHODS: This was a multicentre RCT. The IPP strategy comprised modified patient positioning, deep neuromuscular blockade, and abdominal wall prestretching targeting the lowest intra-abdominal pressure (IAP) that maintained acceptable workspace. The SPP strategy comprised patient positioning according to the surgeon's preference, moderate neuromuscular blockade and a fixed IAP of 12 mmHg. The primary endpoint was physiological postoperative recovery, assessed by means of the Postoperative Quality of Recovery Scale. Secondary endpoints included recovery in other domains and overall recovery, the occurrence of intraoperative and postoperative complications, duration of hospital stay, and plasma markers of inflammation up to postoperative day 3. RESULTS: Of 166 patients, 85 received an IPP strategy and 81 an SPP strategy. The IPP strategy was associated with a higher probability of physiological recovery (odds ratio (OR) 2·77, 95 per cent c.i. 1·19 to 6·40, P = 0·017; risk ratio (RR) 1·82, 1·79 to 1·87, P = 0·049). The IPP strategy was also associated with a higher probability of emotional (P = 0·013) and overall (P = 0·011) recovery. Intraoperative adverse events were less frequent with the IPP strategy (P < 0·001) and the plasma neutrophil-lymphocyte ratio was lower (P = 0·029). Other endpoints were not affected. CONCLUSION: In this cohort of patients undergoing laparoscopic colorectal surgery, an IPP strategy was associated with faster recovery, fewer intraoperative complications and less inflammation than an SPP strategy. Registration number: NCT02773173 ( http://www.clinicaltrials.gov).

ANTECEDENTES: No se sabe con certeza si individualizar las presiones del neumoperitoneo durante la cirugía laparoscópica mejora la recuperación postoperatoria. Comparamos una estrategia con individualización de la presión del neumoperitoneo (individualised pneumoperitoneum pressure, IPP) frente a una estrategia con presión estándar del neumoperitoneo (standard pneumoperitoneum pressure, SPP) respecto a la recuperación postoperatoria tras cirugía colorrectal laparoscópica. MÉTODOS: Ensayo clínico aleatorizado multicéntrico. La estrategia IPP consistió en una modificación de la posición, bloqueo neuromuscular profundo, y una distensión de la pared abdominal conseguida con la presión intraabdominal (intra-abdominal pressure, IAP) más baja en la que el espacio quirúrgico operativo siguiera siendo aceptable. La estrategia SPP consistió en una posición de acuerdo con la preferencia del cirujano, bloqueo neuromuscular moderado, e IAP fija de 12 mm Hg. El resultado primario fue la recuperación fisiológica postoperatoria, evaluada mediante la escala de calidad en la recuperación postoperatoria (Postoperative Quality of Recovery Scale, PQRS). Los resultados secundarios incluyeron la recuperación en otros dominios y la recuperación global, la aparición de complicaciones intraoperatorias y postoperatorias, duración de la estancia hospitalaria, y los valores de los marcadores inflamatorios séricos durante tres días postoperatorios. RESULTADOS: De un total de 166 pacientes, 85 recibieron una estrategia IPP y 81 una estrategia SPP. La estrategia IPP se asoció con una elevada probabilidad de recuperación fisiológica (razón de oportunidades, odds ratio OR, 2,8 (i.c. del 95% 1,2-6,4); P = 0,017, razón de riesgo, 1,8 (i.c. del 95% 1,7-1,9), P = 0,05)). La estrategia IPP también se asoció con una elevada probabilidad de recuperación emotiva (P = 0,013) y global (P = 0,011). Los eventos adversos intraoperatorios fueron menos frecuentes con la estrategia IPP (P < 0,001) y la tasa neutrófilo-linfocito fue más baja (P = 0,029). No se observaron cambios en otras variables. CONCLUSIÓN: En esta cohorte de pacientes sometidos a cirugía colorrectal laparoscópica, una estrategia IPP se asoció con una recuperación más rápida, menos complicaciones intraoperatorias y menos inflamación en comparación con una estrategia SPP.

Defining the landscape of ATP-competitive inhibitor resistance residues in protein kinases.

Kinases are involved in disease development and modulation of their activity can be therapeutically beneficial. Drug-resistant mutant kinases are valuable tools in drug discovery efforts, but the prediction of mutants across the kinome is challenging. Here, we generate deep mutational scanning data to identify mutant mammalian kinases that drive resistance to clinically relevant inhibitors. We aggregate these data with subsaturation mutagenesis data and use it to develop, test and validate a framework to prospectively identify residues that mediate kinase activity and drug resistance across the kinome. We validate predicted resistance mutations in CDK4, CDK6, ERK2, EGFR and HER2. Capitalizing on a highly predictable residue, we generate resistance mutations in TBK1, CSNK2A1 and BRAF. Unexpectedly, we uncover a potentially generalizable activation site that mediates drug resistance and confirm its impact in BRAF, EGFR, HER2 and MEK1. We anticipate that the identification of these residues will enable the broad interrogation of the kinome and its inhibitors.

Contribución a la restauración y el mantenimiento de obras de importancia histórica, cultural y social de la ciudad de La Habana / Contribution to the restoration and maintenance of works of historical, cultural and social importance of the city of Havana

RESUMEN Entre las aplicaciones de la Ciencia e Ingeniería de Materiales que realiza el Centro de Aplicaciones Tecnológicas y Desarrollo Nuclear CEADEN está el apoyo mediante varias técnicas físicas a la restauración y el mantenimiento de estructuras y objetos de la ciudad de La Habana que poseen interés histórico, cultural y social . En el presente trabajo es abordado el campo de la Defectoscopía, en lo cual los Ensayos no destructivos aplicados tributaron a la restauración del patrimonio cultural, a la mejora de instalaciones deportivas de la capital y, en mayor medida, a la seguridad de instalaciones de interés social como son los parques de diversión. En ese sentido se presentan la inspección de estructuras en el marco de la restauración de la Sala Cabildo del Museo de la Ciudad de La Habana en el Palacio de los Capitanes Generales en La Habana Vieja; el diagnóstico de uniones soldadas durante la restauración de la iluminación y la instalación de la pantalla gigante del Estadio Latinoamericano del Cerro y la Inspección realizada sistemáticamente en mantenimiento a elementos críticos de equipos de los parques de diversión.

ABSTRACT Among the applications of Materials Science and Engineering carried out by the Center for Technological Applications and Nuclear Development (CEADEN) / Centro de Aplicaciones Tecnológicas y Desarrollo Nuclear CEADEN is the use of various physical techniques to support the restoration and maintenance of buildings and other work objects of historical, cultural and social interest in Havana city. The field of Defectoscopy is addressed in this paper, where the applied Nondestructive testings also contributed to restore the cultural heritage, to upgrade the structural conditions at an important sport facility in Havana, and in a greater extent, to the safety of facilities of social significance, such as amusement parks. In this regard, three examples are presented: the inspection of structures during the restoration of the City Hall in the Museum of the Havana City at the Palace of Captains General; the welded joints testing during the restoration of the lighting system and the installation of the digital screen at the Latin American Stadium in Cerro municipality; and finally, the inspection systematically performed at maintenance works to critical elements and related devices at amusement parks.

Data extracted from olive oil mill waste exposed to ambient conditions.

Recent studies show that the process of extraction of olive oil results in a large amount of waste. Around 20% the oil is obtained in the process and the remaining 80% corresponds to mainly two types of waste, known as orujo and alperujo. These residues were stored in pools for 6 months in an uncontrolled environment. The reservoirs are open and generate Odorous Volatile Organic Compounds (VOCs) as products of waste decomposition. The data in this article corresponds of physical-chemical compounds of olive oil mill waste exposed to ambient conditions. The data was obtained from two different oil mills, namely, Almazara del Pacífico located in the Alto Pangue area, Talca, Chile; and Agricola y Forestal Don Rafael oil mill, Molina, Chile. Samples were extracted directly from the oil mills to fill 200 L plastic containers that simulated the waste storage in oil mill reservoirs. Each sample was identified and standardized to a mass of 150 kg and moved and stored under uncontrolled ambient conditions at the Universidad de Talca, Curicó, Chile.

Bcl-2 expression in a diabetic embryopathy model in presence of polyamines.

The frequency of congenital malformations is 3-5 times higher in mothers with pregestational diabetes mellitus than in general population. Apparently, this problem is due to change in the expression of apoptotic and antiapoptotic genes induced by the oxidative stress derived from the diabetes/hyperglycemia. One of these genes is Bcl-2, which is associated with the control and inhibition of apoptosis. The purpose of the present work was to study the effect of polyamine addition over expression of Bcl-2 gene in a model of diabetic embryopathy. For this, gestational day 10.5 (GD10.5) rat embryos were incubated at 37°C for 24 h in control medium, medium with high glucose, or medium with high glucose and supplemented with spermidine or spermine. Post-cultured embryos were harvested and observed to obtain morphological scores; some of them were subjected to molecular biology studies: DNA isolation plus conventional PCR or RNA isolation plus RT-PCR; other embryos were fixed with paraformaldehyde and used for immunohistochemical detection of Bcl-2 protein. Although Bcl-2 mRNA was similarly expressed in all rat embryo treatments, Bcl-2 protein was found only in control-incubated embryos. In conclusion, it seems that the inhibition of Bcl-2 gene expression induced by glucose was not reversed by polyamines.

Impact of rectum and bladder anatomy in intrafractional prostate motion during hypofractionated radiation therapy.

BACKGROUND: The objective was to determine the magnitude of the prostate intrafractional motion relative to bony pelvis anatomy, and to evaluate the relationship between this displacement and some clinical and anatomical variables. MATERIALS AND METHODS: The prospective study consisted of 544 images (375 pre-treatment CBCT and 169 post-treatment CBCT) from 15 prostate adenocarcinoma patients that were used for intrafractional prostate motion determination. In addition, two radiation oncologists re-contoured the bladder and rectum on each CBCT according to the patient's anatomy of the day. ANOVA and correlation analysis followed by linear regression analysis were performed to identify clinical or anatomical variables that predict large prostate intrafractional motion. RESULTS: Prostate shift increased in patients with hormone therapy (p ≤ 0.02). The regression analysis showed that patients with large bladder intrafractional filling (p < 0.01) and a large bladder volume difference from planning CT were more likely to experience bigger longitudinal prostate motion (> 3 mm). Recommended bladder size values: anterior-posterior size ≤ 10 cm and anterior-posterior/cranio-caudal ratio ≤ 1.7, both parameters measured in the midsagittal prostate plane, were defined. CONCLUSIONS: The treatment margin should not be reduced for those patients who were treated with hormone therapy and/or whose rectum or bladder was far from complying the preparation protocol conditions.

Evolution of physical-chemical parameters, microbial diversity and VOC emissions of olive oil mill waste exposed to ambient conditions in open reservoirs.

In the olive oil extraction process, 20% olive oil is obtained. About 80% corresponds to waste, mainly alperujo and orujo. When these residues are stored in open reservoirs for later stabilization or potential reuse, odorous Volatile Organic Compounds (VOCs) are generated as products of waste decomposition. In this work, these emissions were studied by means of TD-GC/MS in relation to the changes in the physical-chemical (ashes, moisture, total phenols, pH, proteins, fibers, oils, fats) and biological parameters (bacterial and fungal diversity in Illumina platform) of waste for 6 months. The dynamics of these parameters were statistically related to the evolution of environmental variables (temperature, relative humidity, precipitation) and their effects on the most relevant physical-chemical parameters in order to evaluate their incidence in odorant VOCs emissions over time. The results showed a progressive increase in the diversity of both fungi and bacteria that were related, mainly, to a progressive decrease in the concentration of fatty acid methyl esters and the concentration of alkenes in the emissions; and to an increase of odorous compounds, mainly aldehydes, ketones and carboxylic acids, which were responsible for the unpleasant odors of waste. No significant differences were observed between the evolution of orujo characteristics compared to those of alperujo.

High frequency of Taenia pisiformis metacestodes and high sex-associated susceptibility to cysticercosis in naturally infected wild rabbits.

Sexual dimorphism is a well-documented phenomenon observed at all levels of the animal kingdom, with the inclusion of both sexes in clinical trials and basic research becoming mandatory. Regarding parasitosis, in several animal species, the signs and virulence of the disease may change depending on the sex of the affected animal. In the cestodiasis caused by Taenia solium and Taenia crassiceps, females are more susceptible to experimental infection than males. Cysticercosis by Taenia pisiformis in rabbits has acquired relevance due to its economic impact, namely affecting welfare and production. In America, specifically in Mexico, there are no formal reports on the infection with T. pisiformis metacestodes in populations of wild rabbits, despite being the country with more endemic species (about 15 species), among them, the volcanoes rabbits or the endangered teporingo (Romerolagus diazi). In this study, 31 wild rabbits were obtained by hunters of some regions of Morelos state during several hunting seasons, and sex, physiological stage, and number of metacestodes were recorded. A high frequency of infection by T. pisiformis metacestodes (67.7%) was found. Also, a higher susceptibility to this infection was observed in does (80% infected) compared to bucks (40%), finding 84.2% of metacestodes (235 metacestodes) in does and 15.8% of metacestodes (44 metacestodes) in bucks. The percentage of infection was higher in lactating compared with pregnant and non-pregnant does, with metacestodes lodging mainly in the uterus. Increasing our knowledge regarding parasitic infections can help us better understand transmission circles as well as the parasite-host interaction of these increasingly at risk rabbit species.

Safety and efficacy of small bowel polypectomy using a balloon-assisted enteroscope in pediatric patients with Peutz-Jeghers syndrome. / Seguridad y eficacia de la polipectomía en intestino delgado utilizando enteroscopio asistido por balones en pacientes pediátricos con síndrome de Peutz-Jeghers.

INTRODUCTION AND AIMS: Peutz-Jeghers syndrome is an autosomal dominant inherited pathology characterized by gastrointestinal hamartomatous polyps, predominantly in the small bowel, and pigmented mucocutaneous lesions. Guidelines suggest polypectomy with a balloon-assisted enteroscope when polyps are larger than 10mm. Complications in adults can be as high as 6.8%, but there is little information on pediatric populations. Our aim was to describe the safety and efficacy of polypectomy in a group of pediatric patients with Peutz-Jeghers syndrome using balloon-assisted enteroscopy. MATERIALS AND METHODS: A retrospective study was conducted at the Hospital de Especialidades del Centro Médico Nacional Siglo XXI on pediatric patients with Peutz-Jeghers syndrome that required balloon-assisted enteroscopy and polypectomy within the time frame of January 2010 and December 2015. Patients that underwent polypectomy with a push enteroscope were excluded from the study. RESULTS: A total of 35 polypectomies were performed on 4 patients (female/male: 3/1). The mean age of the patients was 13.7 years (range:11-16). Twelve enteroscopies were carried out, 8 of which were anterograde. A single-balloon enteroscope was used in 7 procedures and a double-balloon enteroscope in 5. The mean size of the polyps was 1.6cm (range: 1-4cm). A major complication (acute pancreatitis) presented in only one case (8.3%). No other major complications associated with the procedures were observed. CONCLUSION: Balloon-assisted enteroscopy with polypectomy in children is a safe and effective procedure, with complications similar to those reported in adults.

Multinational case-control study of risk factors for the development of late invasive pulmonary aspergillosis following kidney transplantation.

OBJECTIVES: To assess the risk factors for development of late-onset invasive pulmonary aspergillosis (IPA) after kidney transplantation (KT). METHODS: We performed a multinational case-control study that retrospectively recruited 112 KT recipients diagnosed with IPA between 2000 and 2013. Controls were matched (1:1 ratio) by centre and date of transplantation. Immunosuppression-related events (IREs) included the occurrence of non-ventilator-associated pneumonia, tuberculosis, cytomegalovirus disease, and/or de novo malignancy. RESULTS: We identified 61 cases of late (>180 days after transplantation) IPA from 24 participating centres (accounting for 54.5% (61/112) of all cases included in the overall study). Most diagnoses (54.1% (33/61)) were established within the first 36 post-transplant months, although five cases occurred more than 10 years after transplantation. Overall mortality among cases was 47.5% (29/61). Compared with controls, cases were significantly older (p 0.010) and more likely to have pre-transplant chronic obstructive pulmonary disease (p 0.001) and a diagnosis of bloodstream infection (p 0.016) and IRE (p <0.001) within the 6 months prior to the onset of late IPA. After multivariate adjustment, previous occurrence of IRE (OR 19.26; 95% CI 2.07-179.46; p 0.009) was identified as an independent risk factor for late IPA. CONCLUSION: More than half of IPA cases after KT occur beyond the sixth month, with some of them presenting very late. Late IPA entails a poor prognosis. We identified some risk factors that could help the clinician to delimit the subgroup of KT recipients at the highest risk for late IPA.

Alterations of antitumor and metabolic responses in L5178Y-R lymphoma-bearing mice after only 30-minute daily chronic stress exposure.

AIM: In stress research, reducing times of stress induction may contribute to improving the well-being of experimental animals, especially in cancer models, already under physiological distress. To support this idea, we evaluated the effects of a short-timed stress protocol on endocrine, metabolic and immune indicators in mice bearing the L5178Y-R lymphoma. MATERIALS AND METHODS: A 30-minute daily stress protocol was applied for 28 days to healthy and lymphoma-bearing BALB/c mice; body weight, plasma levels of corticosterone, norepinephrine, Th1/Th2 cytokines, insulin, and leptin, were measured. RESULTS: We found a 12% significant decrease in body weight in non-tumor bearing mice under stress (p < 0.007). The disruption of weight evolution was accompanied by a stress induced 85% decrease in plasmatic leptin (p < 0.01) and total reduction of insulin. Tumor burden alone was associated to an increase in more than two-fold of plasmatic levels of norepinephrine (p < 0.008). Neither stress nor tumor or their combination, resulted in an elevation of systemic IL-6. IFN-γ levels were 20 times higher in lymphoma-bearing animals when compared with non-tumor bearing mice (p < 0.01); however, under stress, this response was reduced by half, indicating a suppressing effect of chronic stress on the antitumor immune response. CONCLUSION: A short-timed stress induction is enough to cause significant alterations in the metabolism and immunity of healthy and tumor-bearing mice, supporting the use of short-timed protocols as an efficient way to induce chronic stress that also considers concerns regarding the well-being of experimental animals in biomedical research.