[Utility of the medial region of pro-adrenomodulin for the detection of true bacteremia in elderly patients treated in the emergency department for suspected infection]. / Utilidad de la región medial de la pro-adrenomodulina para la detección de bacteriemia verdadera en pacientes mayores atendidos en urgencias por sospecha de infección.

OBJECTIVE: The prediction of bacteremia in the emergency department (ER) is important for initial decision-making. The elderly population is a diagnosis challenge. The objective was to evaluate the accuracy of mid regional pro-adrenomedullin (MR-proADM) to identify true bacteremia (BV) in elderly patients attended in 3 hospital emergency departments. METHODS: Observational study including patients ≥75 years of age or older attended in the ER for suspected infection in whom a blood culture (BC) was extracted. Sociodemographic, comorbidity, hemodynamic and analytical variables, biomarkers [MR-proADM, procalcitonin (PCT), C-reactive protein (CRP) and lactate] and final diagnosis were collected. The primary outcome was a true positive on a blood culture. RESULTS: A total of 109 patients with a mean age of 83 (SD: 5.5) years were included. A final diagnosis of BV was obtained in 22 patients (20.2%). The independent variables to predict it were PCT (OR: 13.9; CI95%: 2.702-71.703; p=0.002), MR-proADM (OR: 4.081; CI95%: 1.026-16.225; p=0.046) and temperature (OR: 2.171; CI95%: 1.109-4.248; p=0.024). Considering the cut-off point for MR-proADM (2.13 mg/dl), a sensitivity (Se) of 73%, specificity (E) of 71%, a positive predictive value (PPV) of 39%, a negative predictive value (NPV) of 91%, a positive likelihood ratio (LHR+) of 2.53 and a negative likelihood ratio (LHR-) of 0.38; for PCT (0.76 mg/dl) a Se of 90%, E of 65%, PPV of 40%, NPV of 96%, LHR+ 2,64 and a LHR- of 0.14 were obtained. When combining both, a Se of 69%, E of 84%, PPV of 52%, NPV of 91%, LHR+ of 4.24 and LHR- of 0.38 were observed. CONCLUSIONS: Elevated levels of PCT and MR-proADM were independently associated with an increased risk of BV and the combination of both improves the accuracy to identify these patients.

A Genetically Heterogeneous Rat Model with Divergent Mitochondrial Genomes.

We generated a genetically heterogenous rat model by a 4-way cross strategy using 4 inbred strains (Brown Norway [BN], Fischer 344 [F344], Lewis [LEW], and Wistar Kyoto [KY]) to provide investigators with a highly genetically diverse rat model from commercially available inbred rats. We made reciprocal crosses between males and females from the 2 F1 hybrids to generate genetically heterogeneous rats with mitochondrial genomes from either the BN (OKC-HETB, a.k.a "B" genotype) or WKY (OKC-HETW a.k.a "W" genotype) parental strains. These two mitochondrial genomes differ at 94 nucleotides, more akin to human mitochondrial genome diversity than that available in classical laboratory mouse strains. Body weights of the B and W genotypes were similar. However, mitochondrial genotype antagonistically affected grip strength and treadmill endurance in females only. In addition, mitochondrial genotype significantly affected multiple responses to a high-fat diet (HFD) and treatment with 17α-estradiol. Contrary to findings in mice in which males only are affected by 17α-estradiol supplementation, female rats fed a HFD beneficially responded to 17α-estradiol treatment as evidenced by declines in body mass, adiposity, and liver mass. Male rats, by contrast, differed in a mitochondrial genotype-specific manner, with only B males responding to 17α-estradiol treatment. Mitochondrial genotype and sex differences were also observed in features of brain-specific antioxidant response to a HFD and 17α-estradiol as shown by hippocampal levels of Sod2 acetylation, JNK, and FoxO3a. These results emphasize the importance of mitochondrial genotype in assessing responses to putative interventions in aging processes.

Antigen-Specific CD4+ T-Cell Activation in Primary Antibody Deficiency After BNT162b2 mRNA COVID-19 Vaccination.

Previous studies on immune responses following COVID-19 vaccination in patients with common variable immunodeficiency (CVID) were inconclusive with respect to the ability of the patients to produce vaccine-specific IgG antibodies, while patients with milder forms of primary antibody deficiency such as immunoglobulin isotype deficiency or selective antibody deficiency have not been studied at all. In this study we examined antigen-specific activation of CXCR5-positive and CXCR5-negative CD4+ memory cells and also isotype-specific and functional antibody responses in patients with CVID as compared to other milder forms of primary antibody deficiency and healthy controls six weeks after the second dose of BNT162b2 vaccine against SARS-CoV-2. Expression of the activation markers CD25 and CD134 was examined by multi-color flow cytometry on CD4+ T cell subsets stimulated with SARS-CoV-2 spike peptides, while in parallel IgG and IgA antibodies and surrogate virus neutralization antibodies against SARS-CoV-2 spike protein were measured by ELISA. The results show that in CVID and patients with other milder forms of antibody deficiency normal IgG responses (titers of spike protein-specific IgG three times the detection limit or more) were associated with intact vaccine-specific activation of CXCR5-negative CD4+ memory T cells, despite defective activation of circulating T follicular helper cells. In contrast, CVID IgG nonresponders showed defective vaccine-specific and superantigen-induced activation of both CD4+T cell subsets. In conclusion, impaired TCR-mediated activation of CXCR5-negative CD4+ memory T cells following stimulation with vaccine antigen or superantigen identifies patients with primary antibody deficiency and impaired IgG responses after BNT162b2 vaccination.

Effectiveness of a polyphenolic extract (Lippia citriodora and Hibiscus sabdariffa) on appetite regulation in overweight and obese grade I population: an 8-week randomized, double-blind, cross-over, placebo-controlled trial.

INTRODUCTION: Polyphenols have shown capacity to improve appetite sensation, leading to enhanced control of body weight. However, despite being related with hunger-related hormones, metabolic and mechanism are not well known. METHODS: The effectiveness of a nutraceutical composed of extract to Lippia citriodora and Hibiscus sabdarrifa (Lc-Hs) for controlling satiety and hunger was analyzed in a cross-over, placebo-controlled (Pla) clinical intervention. The study was divided in two 60-day periods separated by 30-day length wash-out period. At the end of each period, overweight and obese subjects (n = 33; age = 33.76 ± 12.23; BMI = 28.20 kg/m2 ± 2.47; fat mass 30.65 ± 8.39%; both sexes were proposed to eat an ad-libitum meal. Meanwhile, appetite sensation was determined by visual analog scales at different times. Moreover, blood extraction was performed to determine biochemical parameters (lipid and glucidic profile and safety parameters) and to evaluate hunger-related hormones (insulin, leptin, ghrelin, adiponectin, GLP-1 and peptide YY). RESULTS: A decrease in appetite sensation was observed in Lc-Hs treatment, showing higher satiety quotient (Pla = 3.36 ± 2.33%mm/kcal; Lc-Hs = 5.53 ± 2.91%mm/kcal; p < 0.0001). Area under the curve was higher in Pla compared to Lc-Hs during the test, from baseline to minute 240 (240 (Pla 9136.65 ± 2261.46% x min-1; Lc-Hs 8279.73 ± 2745.71% x min-1; p < 0.014). Energy consumption was lower for subjects treated with Lc-Hs (774.44 ± 247.77 kcal) compared to those treated with Pla (849.52 ± 246.54 kcal) (p < 0.004). Leptin values varied from baseline (Pla 12.36 ± 1.98 ng/mL; Lc-Hs 13.13 ± 1.99 ng/mL) to the end of the study (Pla 12.60 ± 2.02 ng/mL; Lc-Hs 12.06 ± 2.05 ng/mL; p < 0.047). GLP-1 values varied (p < 0.001) in Lc-Hs treatment from baseline (4.34 ± 0.49 ng/mL) to the end of the study (3.23 ± 0.52 ng/mL). CONCLUSION: The supplementation with the Lc-Hs extract decreases appetite sensation in overweight and obese population, reducing calorie intake after an ad-libitum meal. Due to variation on hunger-related hormones and the relationship between satiety feeling, it would be interesting to develop future research focused on the variation of the hormones themselves.

New standards at European Union level on water reuse for agricultural irrigation: Are the Spanish wastewater treatment plants ready to produce and distribute reclaimed water within the minimum quality requirements?

The new European regulation on minimum quality requirements (MQR) for water reuse (EU, 2020/741) was launched in May 2020 and describes the directives for the use of reclaimed water for agricultural irrigation. This Regulation will be directly applicable in all Member States from 26 June 2023. Since its publication in 2020, concerns have raised about potential non-compliance situations in water reuse systems. The present study represents a case study where three different water reuse systems have been monitored to establish their compliance with the MQR. Each water reuse system includes a wastewater treatment plant (WWTP), a distribution/storage system and an end-user point, where water is used for irrigation of leafy greens. The selected water reuse systems allowed us to compare the efficacy of water treatments implemented in two WWTPs as well as the impact of three different irrigation systems (drip, furrow and overhead irrigation). The presence and concentration of indicator microorganisms (Escherichia coli and C. perfringens spores) as well as pathogenic bacteria (Shiga toxin-producing, E. coli (STEC), E. coli O157:H7, and Salmonella spp.) were monitored in different sampling points (influent and effluent of the WWTPs, water reservoirs located at the distribution system and the end-user point at the irrigation system as well as in the leafy greens during their growing cycle. Average levels of E. coli (0.73 ± 1.20 log cfu E. coli/100 mL) obtained at the point where the WWTP operator delivers reclaimed water to the next actor in the chain, defined in the European regulation as the 'point of compliance', were within the established MQR (<1 log cfu/100 mL) (EU, 2020/741). On the other hand, average levels of E. coli at the end-user point (1.0 ± 1.2 log cfu/100 mL) were below the recommended threshold (2 log cfu E. coli/100 mL) for irrigation water based on the guidance document on microbiological risks in fresh fruits and vegetables at primary production (EC, 2017/C_163/01). However, several outlier points were observed among the samples taken at the irrigation point, which were linked to a specific cross-contamination event within the distribution/storage system. Regarding pathogenic bacteria, water samples from the influent of the WWTPs showed a 100% prevalence, while only 5% of the effluent samples were positive for any of the monitored pathogenic bacteria. Obtained results indicate that reclaimed water produced in the selected water reuse system is suitable to be used as irrigation water. However, efforts are necessary not only in the establishment of advance disinfection treatments but also in the maintenance of the distribution/storage systems.

Circadian disruption promotes tumor-immune microenvironment remodeling favoring tumor cell proliferation.

Circadian disruption negatively affects physiology, posing a global health threat that manifests in proliferative, metabolic, and immune diseases, among others. Because outputs of the circadian clock regulate daily fluctuations in the immune response, we determined whether circadian disruption results in tumor-associated immune cell remodeling, facilitating tumor growth. Our findings show that tumor growth rate increased and latency decreased under circadian disruption conditions compared to normal light-dark (LD) schedules in a murine melanoma model. Circadian disruption induced the loss or inversion of daily patterns of M1 (proinflammatory) and M2 (anti-inflammatory) macrophages and cytokine levels in spleen and tumor tissues. Circadian disruption also induced (i) deregulation of rhythmic expression of clock genes and (ii) of cyclin genes in the liver, (iii) increased CcnA2 levels in the tumor, and (iv) dampened expression of the cell cycle inhibitor p21WAF/CIP1 , all of which contribute to a proliferative phenotype.

Doublecortin-like kinase 1 promotes hepatocyte clonogenicity and oncogenic programming via non-canonical ß-catenin-dependent mechanism.

Chronic liver injury is a risk factor for cirrhosis and hepatocellular carcinoma (HCC). The molecular mechanisms that regulate the decision between normal injury repair and neoplastic initiation are unclear. Doublecortin-like kinase 1 (DCLK1), a tumor stem cell marker, is induced during cirrhosis and HCC. Here, we demonstrate that DCLK1-overexpressing primary human hepatocytes formed spheroids in suspension cultures. Spheroids derived from DCLK1-overexpressing hepatoma cells showed high level expression of active ß-catenin, α-fetoprotein, and SOX9, suggesting that DCLK1 overexpression induces clonogenicity and dedifferentiated phenotypes in hepatoma cells. DCLK1 overexpression in hepatoma cells also increased phosphorylation of GSK-3ß at Ser9. This was associated with an induction of a 48-kDa active ß-catenin with a preserved hypophosphorylated N-terminus that interacted with nuclear TCF-4 resulting in luciferase reporter activity and cyclin D1 expression. DCLK1 downregulation inhibited 48-kDa ß-catenin expression. The proteasome inhibitor bortezomib did not block the 48-kDa ß-catenin, instead, caused a threefold accumulation, suggesting a proteasome-independent mechanism. Liver tissues from patients with cirrhosis and HCC revealed epithelial co-staining of DCLK1 and active ß-catenin, and cleaved E-cadherin. Repopulated DCLK1-overexpressing primary human hepatocytes in humanized FRG mouse livers demonstrated active ß-catenin. In conclusion, DCLK1 regulates oncogenic signaling and clonogenicity of hepatocytes by a novel non-canonical/atypical ß-catenin-dependent mechanism.

Chronic whipworm infection exacerbates Schistosoma mansoni egg-induced hepatopathology in non-human primates.

BACKGROUND: Schistosomiasis continues to inflict significant morbidity and mortality in the tropical and subtropical regions of the world. The disease endemicity overlaps with the transmission of other parasitic diseases. Despite the ubiquity of polyparasitism in tropical regions, particularly in rural communities, little is known about the impact of multiple helminth infections on disease progression. In this pilot study, we describe the influence of chronic Trichuris trichiura infection on Schistosoma mansoni egg-induced hepatopathology in infected baboons. METHODS: Baboons with or without underlying whipworm infection were challenged with S. mansoni cercariae to establish schistosomiasis. Adult S. mansoni worms were recovered by perfusion and enumerated, hepatic granulomas were quantified via light microscopy, and transcriptional profiling of tissues were completed using RNA sequencing technologies. RESULTS: Co-infection with both S. mansoni and T. trichiura resulted in higher female schistosome worm burden and significantly larger liver granuloma sizes. Systems biology analyses of peripheral blood mononuclear cells (PBMC) revealed pathways associated with increased liver damage in co-infected baboons. CONCLUSIONS: Underlying chronic whipworm infection intensified schistosome egg-induced liver pathology in infected baboons. RNA-Seq analysis provided insight into pathways associated with increased liver damage, corroborating histological findings.

Patología oculoplástica: experiencia de 7 años en Hospital del Sistema de Salud Público de Chile / Oculoplastic Pathology: experience of 7 years in Hospital of the Public Health System of Chile

INTRODUCCIÓN: La cirugía oculoplástica estudia y trata los trastornos de párpados, órbita y vías lagrimales. Entre las patologías más importantes por frecuencia e impacto tenemos: ptosis palpebral, blefarochalasis, ectropión y entropión. OBJETIVO: Analizar la experiencia del Hospital El Pino en cuanto al manejo de patología oculoplástica en manos de un cirujano plástico. MATERIALES Y MÉTODO: Estudio descriptivo y retrospectivo. Se revisaron fichas de pacientes operados con diagnóstico de blefarochalasis, ptosis palpebral, ectropión y entropión entre los años 2010 y 2017. Se analizaron datos como edad, sexo, comorbilidades, causa del defecto, cirugía oculoplástica, tipo de anestesia, complicación posoperatoria, tiempo de seguimiento y resultados. RESULTADOS: Entre los años 2010 y 2017 se operaron 79 pacientes con patología oculoplástica, 17 por ptosis palpebral, 42 por blefarochalasis, 14 por ectropión y 6 por entropión, siendo la principal causa senil (93,7%). Las cirugías realizadas fueron: pexia del elevador para Ptosis palpebral, blefaroplastía para blefarochalasis y para ectropión-entropión tarsal strip. La principal técnica anestésica utilizada fue anestesia local + sedación (54,4%). Entre el total de complicaciones posoperatorias tenemos: lagoftalmo (2 casos), ectropión residual (3 casos), conjuntivitis (3 casos), dehiscencia de herida (2 casos) y hematoma palpebral (1 caso). Se reintervinieron 6 pacientes por complicaciones. Los resultados obtenidos según la evaluación subjetiva del cirujano plástico y pacientes fueron regular (5 casos), bueno (20 casos) y muy bueno (54 casos). CONCLUSIÓN: El manejo de la patología oculoplástica requiere en su mayoría de cirugías ambulatorias con buenos resultados y poca morbilidad, lo cual es factible de realizar en un hospital público. Creemos necesario el uso de algún instrumento objetivo para evaluar de mejor manera los defectos palpebrales y su corrección.

INTRODUCTION: The oculoplastic surgery studies and treats disorders of the eyelids, orbit and lacrimal ways. Among the most important pathologies by frequency and impact are: palpebral ptosis, blepharochalasis, ectropion and entropion. AIM: Analyze the experience of El Pino Hospital regarding the management of oculoplastic pathology in the hands of a plastic surgeon. MATERIALS AND METHOD: Descriptive and retrospective study. We reviewed files of patients operated with diagnosis of blepharochalasis, palpebral ptosis, ectropion and entropion between the years 2010 and 2017. Data were analyzed as age, sex, comorbidities, cause of the defect, oculoplastic surgery, type of anesthesia, postoperative complication, follow-up time and results. RESULTS: Between the years 2010 and 2017, 79 patients with oculoplastic pathology operated, 17 for palpebral ptosis, 42 for blefarochalasis, 14 for ectropion and 6 for entropion, being the main senile cause (93,7%). The surgeries performed were: elevator pexis for palpebral ptosis, blepharoplasty for blefarochalasis and for ectropion-entropion tarsal strip. The main anesthetic technique used was local anesthesia + sedation (54,4%). Among the total postoperative complications, we have: lagophthalmos (2 cases), residual ectropion (3 cases), conjunctivitis (3 cases), wound dehiscence (2 cases) and palpebral hematoma (1 case). Six patients were reoperated due to complications. The results obtained according to the subjective evaluation of the plastic surgeon were regular (5 cases), good (20 cases) and very good (54 cases). CONCLUSION: Management of oculoplastic pathology requires mostly ambulatory surgeries with good results and low morbidity, which is feasible to perform in a public hospital. We believe it is necessary to use some objective instrument to better evaluate the palpebral defects and their correction.

Reconstrucción mamaria con colgajo musculocutáneo de recto abdominal con isla transversa de piel (TRAM): experiencia de 12 años en Hospital El Pino / Breast reconstruction with musculocutaneous flap of abdominal rectus with transverse skin island (TRAM): 12 years of experience at Hospital El Pino

Objetivos: Analizar los resultados de reconstrucción mamaria con colgajo musculocutáneo de recto abdominal con isla transversa de piel (TRAM) en el Servicio de Cirugía del Hospital El Pino. Materiales y Métodos: Estudio retrospectivo de pacientes sometidas a mastectomía por cáncer de mama y posterior reconstrucción con colgajo TRAM pediculado en los últimos 12 años (2005-2017). Resultados: Se realizaron 12 reconstrucciones mamarias, 6 fueron con colgajo TRAM pediculado. La mayoría de las pacientes recibieron tratamiento adyuvante con radioterapia (1 caso), quimioterapia (1 caso), quimioterapia + radioterapia (2 casos). El tiempo transcurrido entre la mastectomía y reconstrucción mamaria fue en promedio de 2,5 años. Se produjeron 4 complicaciones (66,7%) que necesitaron reintervención: hematoma posoperatorio precoz, infección y necrosis grasas de colgajo, dehiscencia de sutura abdominal, necrosis grasa + fibrosis de colgajo TRAM. La evaluación de los resultados fue subjetiva obteniéndose muy buenos resultados en el 66,7% de los casos. No hubo complicaciones en sitio donante. Discusión: El colgajo TRAM pediculado es el tejido autólogo más utilizado en reconstrucción mamaria. Su tasa de complicación es de 26% muy por debajo a lo obtenido en nuestra experiencia. Las principales complicaciones son fibrosis y necrosis grasa de colgajo, pérdida de colgajo, seroma e infección siendo la necrosis grasa la más frecuente en nuestra serie. El uso de colgajo TRAM otorga mayor satisfacción con apariencia, tamaño y sensación del seno. Debido a los resultados obtenidos creemos que el colgajo TRAM pediculado es una excelente alternativa de reconstrucción mamaria en nuestro hospital.

Objectives: To analyze the results of breast reconstruction with musculocutaneous flap of the rectus abdominis with transverse skin island (TRAM) in the Service of Surgery of El Pino Hospital. Materials and Methods: Retrospective study of patients undergoing mastectomy for breast cancer and subsequent reconstruction with pedicled TRAM flap in the last 12 years (2005-2017). Results: 12 mammary reconstructions were performed, 6 were with pedicled TRAM flap. The majority of patients received adjuvant treatment with radiotherapy (1 case), chemotherapy (1 case), chemotherapy + radiotherapy (2 cases). The time elapsed between the mastectomy and breast reconstruction was on average 2.5 years. There were 4 complications (66.7%) that required reintervention: early postoperative hematoma, infection and flap fat necrosis, abdominal suture dehiscence, fat necrosis + TRAM flap fibrosis. The evaluation of the results was subjective, obtaining very good results in 66.7% of the cases. There were no complications in the donor site. Discussion: The pedicled TRAM flap is the most used autologous tissue in breast reconstruction. Its complication rate is 26%, much lower than that obtained in our experience. The main complications are fibrosis and flap fat necrosis, flap loss, seroma and infection, with fat necrosis being the most frequent in our series. The use of TRAM flap gives greater satisfaction with appearance, size and sensation of the breast. Due to the results obtained, we believe that the pedicled TRAM flap is an excellent alternative for breast reconstruction in our hospital.

Long-term cytokine and growth factor release from equine platelet-rich fibrin clots obtained with two different centrifugation protocols.

OBJECTIVES: To compare the temporal release (over three weeks) of tumor necrosis factor alpha (TNF-α), interleukin 4 (IL-4), IL-1 receptor antagonist (IL-1ra), platelet-derived growth factor BB (PDGF-BB) and transforming growth factor beta-1 (TGF-ß1) from two platelet-rich fibrin (PRF) preparations from equine blood obtained at either 240g/8min or 416g/10min. METHODS: Whole blood from 10 horses was used to obtain PRF clots by two different centrifugation protocols. After 1h of rest, PRF clots were deposited in wells with culture medium, which was changed at 6h, 24h and then every 48h to 21days. Cytokines and GFs were measured by ELISA at 1h (serum supernatants from PRF clots) and all time points of culture medium change. A negative control (plasma) and a positive control (blood lysate) were also included. RESULTS: There were no relevant differences between the two protocols for the temporal release of proteins. However, a significant (p=0.01) effect of time was noted. All cytokines were detected after 6h of PRF clot culture until day 21. GF were detected at 1h until day 21. The concentrations for these proteins diminished gradually over time. A highly significant (p=0.01) correlation was noticed between all the proteins evaluated. CONCLUSIONS: Leukocytes enmeshed in PRF clots were able to produce cytokines, TGF-ß1 and PDGF-BB. These findings demonstrate a paramount role of leukocytes in wound healing induced or modified by PRF clots in mammals.

PBN (Phenyl-N-Tert-Butylnitrone)-Derivatives Are Effective in Slowing the Visual Cycle and Rhodopsin Regeneration and in Protecting the Retina from Light-Induced Damage.

A2E and related toxic molecules are part of lipofuscin found in the retinal pigment epithelial (RPE) cells in eyes affected by Stargardt's disease, age-related macular degeneration (AMD), and other retinal degenerations. A novel therapeutic approach for treating such degenerations involves slowing down the visual cycle, which could reduce the amount of A2E in the RPE. This can be accomplished by inhibiting RPE65, which produces 11-cis-retinol from all-trans-retinyl esters. We recently showed that phenyl-N-tert-butylnitrone (PBN) inhibits RPE65 enzyme activity in RPE cells. In this study we show that like PBN, certain PBN-derivatives (PBNDs) such as 4-F-PBN, 4-CF3-PBN, 3,4-di-F-PBN, and 4-CH3-PBN can inhibit RPE65 and synthesis of 11-cis-retinol in in vitro assays using bovine RPE microsomes. We further demonstrate that systemic (intraperitoneal, IP) administration of these PBNDs protect the rat retina from light damage. Electroretinography (ERG) and histological analysis showed that rats treated with PBNDs retained ~90% of their photoreceptor cells compared to a complete loss of function and 90% loss of photoreceptors in the central retina in rats treated with vehicle/control injections. Topically applied PBN and PBNDs also significantly slowed the rate of the visual cycle in mouse and baboon eyes. One hour dark adaptation resulted in 75-80% recovery of bleachable rhodopsin in control/vehicle treated mice. Eye drops of 5% 4-CH3-PBN were most effective, inhibiting the regeneration of bleachable rhodopsin significantly (60% compared to vehicle control). In addition, a 10% concentration of PBN and 5% concentration of 4-CH3-PBN in baboon eyes inhibited the visual cycle by 60% and by 30%, respectively. We have identified a group of PBN related nitrones that can reach the target tissue (RPE) by systemic and topical application and slow the rate of rhodopsin regeneration and therefore the visual cycle in mouse and baboon eyes. PBNDs can also protect the rat retina from light damage. There is potential in developing these compounds as preventative therapeutics for the treatment of human retinal degenerations in which the accumulation of lipofuscin may be pathogenic.

Evaluation of a distractor to increase joint space of the stifle joint in dogs: a cadaveric study.

OBJECTIVE: To evaluate the technical feasibility and efficacy of a joint distraction technique to increase the stifle joint space and assess potential soft tissue damage due to the distraction. METHODS: Twenty stifle joints of twelve canine cadavers without evidence of disease were radiographically evaluated by medio-lateral, cranio-caudal and varus-valgus stressed projections. Joint distraction was applied with loads from 40 N up to 200 N, and the joint space achieved was measured on radiographic images. Distraction plus distension with saline was subsequently applied and measured. Varus-valgus stressed projections were repeated after distraction to evaluate a potential increase in joint laxity. RESULTS: Distraction produced a significant increase of the joint space for most of the evaluated loads. Distraction plus distension produced a significant increase for most of the loads compared to the distraction alone. No ensuing joint laxity could be inferred from the post-distraction radiographic evaluation. CLINICAL SIGNIFICANCE: Stifle distraction produces an increase of the joint space, which is wider when intra-articular saline is injected. This may be potentially useful for improving joint structure visualization and facilitating arthroscopic procedures, thus reducing the potential for iatrogenic damage to intra-articular structures. No soft tissue damage could be inferred by radiographic pre- and post-procedure comparison. Further clinical studies are required to evaluate potential neurovascular complications.

Risk factors for tibial tuberosity fracture after tibial tuberosity advancement in dogs.

OBJECTIVE: To retrospectively identify factors that predispose to tibial tuberosity (TT) fracture after tibial tuberosity advancement (TTA) in dogs. METHODS: The medical records and radiographs of a group of control dogs (n = 212) that had TTA surgery (n = 241 procedures) and did not sustain a fracture between 2008 and 2013, and those of 12 dogs that did sustain a fracture (n = 13 procedures) between 2008 and 2013 at two veterinary teaching hospitals were evaluated to determine the effect of signalment, body weight and surgical inaccuracies on TT fracture. Multivariable logistic regression was performed with the occurrence of TT fracture as the outcome variable of interest. RESULTS: Signalment and body weight were not found to be associated with TT fracture. Of the surgical inaccuracies, osteotomy shape (p = 0.003), plate position (p = 0.009), and cage position (p = 0.039) were factors significantly associated with TT fracture. CLINICAL SIGNIFICANCE: This study provides data to support the hypothesis that poor plate position, poor cage position, and narrow distal osteotomy width are associated with TT fracture after TTA. We conclude that it is of paramount importance to pay careful attention to surgical technique in order to reduce this risk.

Evaluation of a joint distractor to facilitate arthroscopy of the hip joint in dogs.

OBJECTIVE: To evaluate the technical feasibility and efficacy of a hip joint distraction technique, any potential ligamentous damage linked to the procedure, and the effect of joint venting on the maximum distraction achieved. METHODS: Twenty hip joints from 11 canine cadavers were evaluated radiographically by standard and stressed projections. Joint distraction was applied with loads from 40 up to 200 N, in 40 N increments, and fluoroscopic images were obtained at each load. At 200 N, a needle was inserted into the joint to achieve a venting effect, and the space was measured again. Standard and stressed radiographs were performed to evaluate potential laxity changes. RESULTS: Distraction caused a significant increase in joint space at each load of distraction, although there were some variations. Joint venting produced a significant increase in joint space. A statistically significant difference in joint laxity evaluated radiographically before and after the procedure was recorded. CLINICAL SIGNIFICANCE: Use of the distraction apparatus resulted in an increase in joint space. This could be useful for clinical situations where a larger joint space is required such as for arthroscopic procedures. However, loads in excess of 200 N may induce significant increases in joint laxity.

Exercise Intensity Guidelines for Cancer Survivors: a Comparison with Reference Values.

The optimal dose of physical activity (PA) in cancer survivors (CS) is unknown due to the large variety of types of cancer, illness stages and treatments, low cardiorespiratory fitness, and physical inactivity. It is recommended that CS follow current PA guidelines for healthy population. There are no specific exercise prescription guidelines for CS. To know the cardiorespiratory parameters of CS in order to create exercise prescription guidelines for this population, 152 inactive CS were recruited to perform a cardiopulmonary exercise test. Peak oxygen uptake (VO2peak), ventilatory threshold (VT) and respiratory compensation point (RCP) determined 3 exercise intensity zones to create exercise intensity classification guidelines for CS. VO2peak (18.7±4.6 mL·kg-1·min-1) and peak heart rate (HRpeak) (145.1±17.9 bpm) were lower than the estimated values (p<0.001). Moderate intensity zone for CS was different from the current PA guidelines for healthy population: 41-64% VO2max, 55-70% HRmax, 23-48% HRres, 2.5-4 METs and 8-14 points on RPE scale. Intensities in PA guidelines for healthy population are not adapted to the characteristics of CS. For individual exercise prescription in CS specific PA guidelines should be used in order to maximize the benefits obtained by the use of aerobic exercise training.

The effects of age and cytomegalovirus on markers of inflammation and lymphocyte populations in captive baboons.

The human immune system undergoes age-related changes that can lead to increased disease susceptibility. Using the baboon as a model for human immune system aging, we examined age-related changes in relative and absolute numbers of T cell subpopulations, cytomegalovirus (CMV) titer and markers of inflammation. In addition, the effect of gender, social status and peer group on lymphocyte subpopulations was determined. Relative and absolute numbers of total lymphocytes (CD3+), T helper cells (CD4+), and cytotoxic T cells (CD8+) increased with age. The proportion of naïve T cells (CD45RA+) decreased, while the total number of cells negative for the co-stimulatory receptor, CD28 (CD28-) increased in an age-dependent manner. Furthermore, CMV titers were negatively correlated with the number of naive CD4+ cells. IL-6 and cortisol concentration were also negatively associated with T cell subpopulations. Additionally, socially dominant baboons exhibited decreases in naïve CD4+ and CD8+ cells (by 65% and 52%, respectively) compared to subordinate animals. These results suggest that factors such as CMV exposure and inflammation may contribute to the age-related decline in immune health and indicate that factors like social status should be considered when studying immunosenescence in animal models.

Manejo anestésico para la realización de biosias transbronquiales guiadas por ecobroncoscopía: descripción de 9 casos y revisión de la literatura / Anesthetic management for performing endobronchial ultrasound-guided transbronchial biopsies: description of 9 cases and literature review

La realización de procedimientos broncoscópicos intervencionistas precisa en muchas ocasiones de la asistencia de anestesiólogos, debido al potencial compromiso de la vía aérea, a la patología asociada y a la complejidad de los procedimientos. Describimos el manejo anestésico de 9 casos de ecobroncoscopias para biopsias de ganglios en cáncer de pulmón, con anestesia intravenosa y sin la necesidad de utilizar dispositivos supraglóticos ni transglóticos, revisando a su vez la literatura al respecto...

Anesthesists are becoming increasingly involved in the performance of interventional bronchoscopies, because of the potential risk of compromising the patency of the airway, the presence of comorbidities ant the global complexity of the procedures. We describe in this paper the anesthetic management of 9 patients scheduled for nodal transbronchial ultrasound guided biopsy with intravenous agents and without the need of supraglotic or transglotic devices...

Characterization of docosahexaenoic acid (DHA)-induced heme oxygenase-1 (HO-1) expression in human cancer cells: the importance of enhanced BTB and CNC homology 1 (Bach1) degradation.

The effect of docosahexaenoic acid (DHA) on heme oxygenase-1 (HO-1) expression in cancer cells has never been characterized. This study examines DHA-induced HO-1 expression in human cancer cell model systems. DHA enhanced HO-1 gene expression in a time- and concentration-dependent manner, with maximal induction at 21 h of treatment. This induction of HO-1 expression was confirmed in vivo using a xenograft nude mouse model fed a fish-oil-enriched diet. The increase in HO-1 gene transcription induced by DHA was significantly attenuated by the antioxidant N-acetyl cysteine, suggesting the involvement of oxidative stress. This was supported by direct measurement of lipid peroxide levels after DHA treatment. Using a human HO-1 gene promoter reporter construct, we identified two antioxidant response elements (AREs) that mediate the DHA-induced increase in HO-1 gene transcription. Knockdown of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) expression compromised the DHA-induced increase in HO-1 gene transcription, indicating the importance of the Nrf2 pathway in this event. However, the nuclear protein levels of Nrf2 remained unchanged upon DHA treatment. Further studies demonstrated that DHA reduces nuclear Bach1 protein expression by promoting its degradation and attenuates Bach1 binding to the AREs in the HO-1 gene promoter. In contrast, DHA enhanced Nrf2 binding to the AREs without affecting nuclear Nrf2 expression levels, indicating a new cellular mechanism that mediates DHA's induction of HO-1 gene transcription. To our knowledge, this is the first characterization of DHA-induced HO-1 expression in human malignant cells.