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Background: The present study was determined the influence of physical activity and dietary habits on lipid profile, blood pressure (BP) and body mass index (BMI) in subjects with metabolic syndrome (MS). Aims: Identify the relationship between physical activity and proper nutrition and the probability of suffering from myocardial infarction (MI). Methods: Hundred chronically ill with MS who were active and followed a healthy diet were classified as compliant, while the remaining subjects were classified as non-compliant. Results: The compliant subjects show lower BMI values (30.8 ± 4.9 vs 32.5 ± 4.6), as well as lower levels of triacylglycerol (130.4 ± 48.2 vs 242.1 ± 90.1), total cholesterol (193.5 ± 39 vs 220.2 ± 52.3) and low-density lipoprotein cholesterol (105.2 ± 38.3 vs 139.2 ± 45). They show higher values in terms of high-density lipoprotein cholesterol levels (62.2 ± 20.1 vs 36.6 ± 15.3), with statistically significant differences. In terms of both systolic and diastolic pressure, no differences were revealed between the groups; however, those who maintain proper dietary habits show lower systolic blood pressure levels than the inactive subjects. The probability of suffering from MI greatly increases among the group of non-compliant subjects. Conclusions: Our results demonstrate how performing aerobic physical activity and following an individualized, Mediterranean diet significantly reduces MS indicators and the chances of suffering from MI.Introducción: En el presente estudio se determinó la influencia de la actividad física y los hábitos nutricionales sobre el perfil lipídico, presión arterial (PA) e índice de masa corporal (IMC) en sujetos con SM. Objetivos: Comprobar la relación entre realizar actividad física y una nutrición adecuada, y la posibilidad de sufrir infarto de miocardio (IM). Método: Se evaluaron 100 sujetos con SM. Los sujetos que manifestaban ser activos y llevaban una alimentación saludable fueron clasificados como cumplidores, mientras que al resto se les clasificó como no cumplidores. Resultados: Los sujetos cumplidores presentan valores menores en cuanto a su IMC (30,8 ± 4,9 vs 32,5 ± 4,6) y sus niveles de triglicéridos (130,4 ± 48,2 vs 242,1 ± 90,1), colesterol total (193,5 ± 39 vs 220,2 ± 52,3) y colesterol unido a lipoproteínas de baja densidad (105,2 ± 38,3 vs 139,2 ± 45); y valores mayores en los niveles de colesterol unido a lipoproteínas de alta densidad (62,2 ± 20,1 vs 36,6 ± 15,3) siendo las diferencias estadísticamente significativas. La PA, tanto sistólica como diastólica, no muestra diferencias entre ambos grupos; en cambio el grupo que manifiesta realizar una alimentación adecuada obtiene unos niveles de presión arterial sistólica menores que el grupo que no la realiza. La posibilidad de padecer IM aumenta significativamente en el grupo de sujetos no cumplidores. Conclusiones: Nuestros resultados muestran como la realización de actividad física de tipo aeróbica y llevar a cabo una alimentación individualizada de tipo mediterráneo reduce significativamente los parámetros relacionados con el SM y las posibilidades de sufrir IM.

Enzymatic DNA synthesis, using stepwise nucleotide addition catalyzed by template-independent polymerases, promises higher efficiency, quality, and sustainability than today's industry-standard phosphoramidite-based processes. We report the directed evolution of a terminal deoxynucleotidyl transferase that uses 3'-phosphate-blocked 2'-deoxynucleoside triphosphates (dNTPs) to control the polymerization reaction. Over 32 iterative rounds of laboratory evolution, 80 amino acid substitutions-constituting ∼20% of the coding protein sequence-were introduced. The engineered polymerase exhibits uniformly high catalytic activity, raising incorporation efficiency by 200-fold to >99% for dNTPs with a 3'-reversible terminator while reducing extension times by >600-fold to 90 s. The same enzyme variant displays improved enzyme robustness, as reflected in the 20°C increase in thermostability. Based on these performance characteristics, the engineered polymerase represents an operational prototype for biocatalytic DNA synthesis at a commercial scale., (© The Author(s) 2025. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Background: Causal graphs are an important tool for covariate selection but there is limited applied research on how best to create them. Here, we used data from the Coronary Drug Project trial to assess a range of approaches to directed acyclic graph (DAG) creation. We focused on the effect of adherence on mortality in the placebo arm, since the true causal effect is believed with a high degree of certainty., Methods: We created DAGs for the effect of placebo adherence on mortality using different approaches for identifying variables and links to include or exclude. For each DAG, we identified minimal adjustment sets of covariates for estimating our causal effect of interest and applied these to analyses of the Coronary Drug Project data., Results: When we used only baseline covariate values to estimate the cumulative effect of placebo adherence on mortality, all adjustment sets performed similarly. The specific choice of covariates had minimal effect on these (biased) point estimates, but including nonconfounding prognostic factors resulted in smaller variance estimates. When we additionally adjusted for time-varying covariates of adherence using inverse probability weighting, covariates identified from the DAG created by focusing on prognostic factors performed best., Conclusion: Theoretical advice on covariate selection suggests that including prognostic factors that are not exposure predictors can reduce variance without increasing bias. In contrast, for exposure predictors that are not prognostic factors, inclusion may result in less bias control. Our results empirically confirm this advice. We recommend that hand-creating DAGs begin with the identification of all potential outcome prognostic factors., Competing Interests: Disclosure: The authors report no conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: ASCO/College of American Pathologists guidelines recommend reporting estrogen receptor (ER) and progesterone receptor (PgR) as positive with (1%-100%) staining. Statistically standardized quantitated positivity could indicate differential associations of positivity with breast cancer outcomes., Methods: MA.27 (ClinicalTrials.gov identifier: NCT00066573) was a phase III adjuvant trial of exemestane versus anastrozole in postmenopausal women with early-stage breast cancer. Immunochemistry ER and PgR HSCORE and % positivity (%+) were centrally assessed by machine image quantitation and statistically standardized to mean 0 and standard deviation (SD) 1 after Box-Cox variance stabilization transformations of square for ER; for PgR, (1) natural logarithm (0.1 added to 0 HSCOREs and 0%+) and (2) square root. Our primary end point was MA.27 distant disease-free survival (DDFS) at a median 4.1-year follow-up, and secondary end point was event-free survival (EFS). Univariate survival with cut points at SDs about a mean of 0 (≤-1; (-1, 0]; (0, 1]; >1) was described with Kaplan-Meier plots and examined with Wilcoxon (Peto-Prentice) test statistic. Adjusted Cox multivariable regressions had two-sided Wald tests and nominal significance P < .05., Results: Of 7,576 women accrued, 3,048 women's tumors had machine-quantitated image analysis results: 2,900 (95%) for ER, 2,726 (89%) for PgR, and 2,582 (85% of 3,048) with both ER and PgR. Higher statistically standardized ER and PgR HSCORE and %+ were associated with better univariate DDFS and EFS ( P < .001). In multivariable assessments, ER HSCORE and %+ were not significantly associated ( P = .52-.88) with DDFS in models with PgR, whereas higher PgR HSCORE and %+ were significantly associated with better DDFS ( P = .001) in models with ER., Conclusion: Adjunctive statistical standardization differentiated quantitated levels of ER and PgR. Patients with higher ER- and PgR-standardized units had superior DDFS compared with those with HSCOREs and %+ ≤-1.

Background: Among bariatric techniques, sleeve gastrectomy (SG) stands out owing to its efficiency. The role of the stomach as a secretory organ of many substances, such as gastrin, related to insulin secretion is well known. Gastrin induces insulin release in isolated pancreatic islets, limiting somatostatin-14 intraislet release, and has been associated with blood glucose level improvement in diabetic models after SG. SG involves gastric resection along the greater curvature. This study aimed to determine the role of gastrin in glucose metabolism improvement after SG with the aid of the gastrin antagonist netazepide., Methods: In 12 sham-operated, 12 SG-operated, and 12 SG-operated/netazepide-treated Wistar rats, we compared medium- and long-term plasma insulin, oral glucose tolerance test (OGTT) results, and plasma gastrin levels. In addition, gastrin expression was assessed in the gastric remnant, and the beta-cell mass was measured., Results: SG induced a medium-term elevation of the insulin response and plasma gastrin levels without modification of the OGTT results. However, long-term depletion of the insulin response with elevated OGTT areas under the curve and plasma gastrin levels appeared after SG. Netazepide prevented the SG effect on these parameters. Gastrin tissue expression was greater in SG animals than in SG/netazepide-treated or control animals. The beta-cell mass was lower in the SG group than in the control or SG/netazepide group., Conclusion: Gastrin plays a central role in glucose improvement after SG. It stimulates a medium-term strong insulin response but also causes long-term beta-cell mass depletion and a loss of insulin response. These effects are prevented by gastrin antagonists such as netazepide., (Copyright © 2024 Society for Surgery of the Alimentary Tract. Published by Elsevier Inc. All rights reserved.)

Purpose: Colorectal cancer is the second leading cause of cancer mortality in the United States. Antiangiogenic therapy with bevacizumab combined with chemotherapy improves survival in previously untreated metastatic colorectal cancer. This study was conducted to determine the effect of bevacizumab (at 10 mg/kg) on survival duration for oxaliplatin-based chemotherapy in patients with previously treated metastatic colorectal cancer., Patients and Methods: Eight hundred twenty-nine metastatic colorectal cancer patients previously treated with a fluoropyrimidine and irinotecan were randomly assigned to one of three treatment groups: oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) with bevacizumab; FOLFOX4 without bevacizumab; or bevacizumab alone. The primary end point was overall survival, with additional determinations of progression-free survival, response, and toxicity., Results: The median duration of survival for the group treated with FOLFOX4 and bevacizumab was 12.9 months compared with 10.8 months for the group treated with FOLFOX4 alone (corresponding hazard ratio for death = 0.75; P = .0011), and 10.2 months for those treated with bevacizumab alone. The median progression-free survival for the group treated with FOLFOX4 in combination with bevacizumab was 7.3 months, compared with 4.7 months for the group treated with FOLFOX4 alone (corresponding hazard ratio for progression = 0.61; P < .0001), and 2.7 months for those treated with bevacizumab alone. The corresponding overall response rates were 22.7%, 8.6%, and 3.3%, respectively ( P < .0001 for FOLFOX4 with bevacizumab v FOLFOX4 comparison). Bevacizumab was associated with hypertension, bleeding, and vomiting., Conclusion: The addition of bevacizumab to oxaliplatin, fluorouracil, and leucovorin improves survival duration for patients with previously treated metastatic colorectal cancer.

Background and Objectives: The validity of brain monitoring using electroencephalography (EEG), particularly to guide care in patients with acute or critical illness, requires that experts can reliably identify seizures and other potentially harmful rhythmic and periodic brain activity, collectively referred to as "ictal-interictal-injury continuum" (IIIC). Previous interrater reliability (IRR) studies are limited by small samples and selection bias. This study was conducted to assess the reliability of experts in identifying IIIC., Methods: This prospective analysis included 30 experts with subspecialty clinical neurophysiology training from 18 institutions. Experts independently scored varying numbers of ten-second EEG segments as "seizure (SZ)," "lateralized periodic discharges (LPDs)," "generalized periodic discharges (GPDs)," "lateralized rhythmic delta activity (LRDA)," "generalized rhythmic delta activity (GRDA)," or "other." EEGs were performed for clinical indications at Massachusetts General Hospital between 2006 and 2020. Primary outcome measures were pairwise IRR (average percent agreement [PA] between pairs of experts) and majority IRR (average PA with group consensus) for each class and beyond chance agreement (κ). Secondary outcomes were calibration of expert scoring to group consensus, and latent trait analysis to investigate contributions of bias and noise to scoring variability., Results: Among 2,711 EEGs, 49% were from women, and the median (IQR) age was 55 (41) years. In total, experts scored 50,697 EEG segments; the median [range] number scored by each expert was 6,287.5 [1,002, 45,267]. Overall pairwise IRR was moderate (PA 52%, κ 42%), and majority IRR was substantial (PA 65%, κ 61%). Noise-bias analysis demonstrated that a single underlying receiver operating curve can account for most variation in experts' false-positive vs true-positive characteristics (median [range] of variance explained ([Formula: see text]): 95 [93, 98]%) and for most variation in experts' precision vs sensitivity characteristics ([Formula: see text]: 75 [59, 89]%). Thus, variation between experts is mostly attributable not to differences in expertise but rather to variation in decision thresholds., Discussion: Our results provide precise estimates of expert reliability from a large and diverse sample and a parsimonious theory to explain the origin of disagreements between experts. The results also establish a standard for how well an automated IIIC classifier must perform to match experts., Classification of Evidence: This study provides Class II evidence that an independent expert review reliably identifies ictal-interictal injury continuum patterns on EEG compared with expert consensus., (© 2022 American Academy of Neurology.)

Background and Objectives: Seizures (SZs) and other SZ-like patterns of brain activity can harm the brain and contribute to in-hospital death, particularly when prolonged. However, experts qualified to interpret EEG data are scarce. Prior attempts to automate this task have been limited by small or inadequately labeled samples and have not convincingly demonstrated generalizable expert-level performance. There exists a critical unmet need for an automated method to classify SZs and other SZ-like events with expert-level reliability. This study was conducted to develop and validate a computer algorithm that matches the reliability and accuracy of experts in identifying SZs and SZ-like events, known as "ictal-interictal-injury continuum" (IIIC) patterns on EEG, including SZs, lateralized and generalized periodic discharges (LPD, GPD), and lateralized and generalized rhythmic delta activity (LRDA, GRDA), and in differentiating these patterns from non-IIIC patterns., Methods: We used 6,095 scalp EEGs from 2,711 patients with and without IIIC events to train a deep neural network, SPaRCNet , to perform IIIC event classification. Independent training and test data sets were generated from 50,697 EEG segments, independently annotated by 20 fellowship-trained neurophysiologists. We assessed whether SPaRCNet performs at or above the sensitivity, specificity, precision, and calibration of fellowship-trained neurophysiologists for identifying IIIC events. Statistical performance was assessed by the calibration index and by the percentage of experts whose operating points were below the model's receiver operating characteristic curves (ROCs) and precision recall curves (PRCs) for the 6 pattern classes., Results: SPaRCNet matches or exceeds most experts in classifying IIIC events based on both calibration and discrimination metrics. For SZ, LPD, GPD, LRDA, GRDA, and "other" classes, SPaRCNet exceeds the following percentages of 20 experts-ROC: 45%, 20%, 50%, 75%, 55%, and 40%; PRC: 50%, 35%, 50%, 90%, 70%, and 45%; and calibration: 95%, 100%, 95%, 100%, 100%, and 80%, respectively., Discussion: SPaRCNet is the first algorithm to match expert performance in detecting SZs and other SZ-like events in a representative sample of EEGs. With further development, SPaRCNet may thus be a valuable tool for an expedited review of EEGs., Classification of Evidence: This study provides Class II evidence that among patients with epilepsy or critical illness undergoing EEG monitoring, SPaRCNet can differentiate (IIIC) patterns from non-IIIC events and expert neurophysiologists., (© 2023 American Academy of Neurology.)

Defects in nucleic acid metabolizing enzymes can lead to spontaneous but selective activation of either cGAS/STING or RIG-like receptor (RLR) signaling, causing type I interferon-driven inflammatory diseases. In these pathophysiological conditions, activation of the DNA sensor cGAS and IFN production are linked to spontaneous DNA damage. Physiological, or tonic, IFN signaling on the other hand is essential to functionally prime nucleic acid sensing pathways. Here, we show that low-level chronic DNA damage in mice lacking the Aicardi-Goutières syndrome gene SAMHD1 reduced tumor-free survival when crossed to a p53-deficient, but not to a DNA mismatch repair-deficient background. Increased DNA damage did not result in higher levels of type I interferon. Instead, we found that the chronic interferon response in SAMHD1-deficient mice was driven by the MDA5/MAVS pathway but required functional priming through the cGAS/STING pathway. Our work positions cGAS/STING upstream of tonic IFN signaling in Samhd1-deficient mice and highlights an important role of the pathway in physiological and pathophysiological innate immune priming., (© 2022 Schumann et al.)

Background: There are data on the safety of cancer surgery and the efficacy of preventive strategies on the prevention of postoperative symptomatic COVID-19 in these patients. But there is little such data for any elective surgery. The main objectives of this study were to examine the safety of bariatric surgery (BS) during the coronavirus disease 2019 (COVID-19) pandemic and to determine the efficacy of perioperative COVID-19 protective strategies on postoperative symptomatic COVID-19 rates., Methods: We conducted an international cohort study to determine all-cause and COVID-19-specific 30-day morbidity and mortality of BS performed between 01/05/2020 and 31/10/2020., Results: Four hundred ninety-nine surgeons from 185 centres in 42 countries provided data on 7704 patients. Elective primary BS (n = 7084) was associated with a 30-day morbidity of 6.76% (n = 479) and a 30-day mortality of 0.14% (n = 10). Emergency BS, revisional BS, insulin-treated type 2 diabetes, and untreated obstructive sleep apnoea were associated with increased complications on multivariable analysis. Forty-three patients developed symptomatic COVID-19 postoperatively, with a higher risk in non-whites. Preoperative self-isolation, preoperative testing for SARS-CoV-2, and surgery in institutions not concurrently treating COVID-19 patients did not reduce the incidence of postoperative COVID-19. Postoperative symptomatic COVID-19 was more likely if the surgery was performed during a COVID-19 peak in that country., Conclusions: BS can be performed safely during the COVID-19 pandemic with appropriate perioperative protocols. There was no relationship between preoperative testing for COVID-19 and self-isolation with symptomatic postoperative COVID-19. The risk of postoperative COVID-19 risk was greater in non-whites or if BS was performed during a local peak., (© 2021. The Author(s).)

Chemotherapy-induced peripheral neuropathy (CIPN) is a common and potentially dose-limiting side effect of neurotoxic chemotherapies. No therapies are available to prevent CIPN. The small number of positive randomized clinical trials (RCTs) evaluating preventive therapies for CIPN provide little guidance to inform the design of future trials. Moreover, the lack of consensus regarding major design features in this area poses challenges to development of new therapies. An Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities and Networks (ACTTION)-Consortium on Clinical Endpoints and Procedures for Peripheral Neuropathy Trials (CONCEPPT) meeting attended by neurologists, oncologists, pharmacists, clinical trialists, statisticians, and regulatory experts was convened to discuss design considerations and provide recommendations for CIPN prevention trials. This article outlines considerations related to design of RCTs that evaluate preventive therapies for CIPN including (1) selection of eligibility criteria (e.g., cancer types, chemotherapy types, inclusion of preexisting neuropathy); (2) selection of outcome measures and endpoints, including those that incorporate alterations in chemotherapy dosing, which may affect the rate of CIPN development and its severity; (3) potential effects of the investigational therapy on the efficacy of chemotherapy; and (4) sample size estimation. Our hope is that attention to the design considerations and recommendations outlined in this article will improve the quality and assay sensitivity of CIPN prevention trials and thereby accelerate the identification of efficacious therapies., (© 2018 American Academy of Neurology.)

An adult Buteo was found dead as a road-kill south of Sacramento, California, and was thought to represent the first state record of the eastern Red-shouldered Hawk ( B. lineatus lineatus ;). It is now a specimen in the Museum of Wildlife and Fisheries Biology (WFB 4816) at the University of California, Davis. We examined this specimen and found that many of its plumage characters differed from all other adult Red-shouldered Hawks examined, including nominate adults. Plumage markings and measurements were intermediate between Red-tailed Hawk ( Buteo jamaicensis, ssp calurus ) and Red-shouldered Hawk (ssp elegans ), leading us to hypothesize that the bird was a hybrid. However, mtDNA sequences and nuDNA microsatellites proved definitively that the bird was a Red-shouldered Hawk, most likely of eastern origin. This case illustrates that apparent hybrids or apparent vagrants could be individuals with anomalous phenotypes caused by rare genetic variation or novel epigenetic effects., Competing Interests: The authors declare there are no competing interests.

Background: Weight regain is common after Roux-en-Y gastric bypass., Objectives: To assess the mechanisms of weight loss after 2 gastrojejunal anastomotic reduction (GJAR) procedures to treat weight regain., Setting: University hospital, United States., Methods: Forty-three Roux-en-Y gastric bypass patients with weight regain were prospectively enrolled. Weight, ghrelin levels, responses to the 21-item three-factor eating questionnaire, and gastrojejunal anastomotic diameter were assessed. Nine patients underwent endoscopic suturing and 34 patients underwent sclerotherapy. At 3 months, weight, ghrelin levels, eating behavior, and outlet diameter were reassessed., Results: Patients were aged 47±10 years and regained 43%±26% of maximal lost weight. Ghrelin levels were 123±106 ng/mL and outlet diameter was 21±6.3 mm. At 3 months, the entire cohort lost 4.1%±5.9% of total weight (TBW) and showed improvement in cognitive eating habits (P<.01). Endoscopic suturing and sclerotherapy patients lost 10.4%±2.2% TBW and 2.7%±5.5% TBW (P<.01), respectively. Suturing and sclerotherapy reduced the outlet diameter by 15.0±6.7 mm and 2.6±5.7 mm (P<.01). Ghrelin levels increased after suturing by 46±55 ng/mL and decreased by 37±110 ng/mL after sclerotherapy (P = .02). Suturing resulted in greater improvement in cognitive eating behavior than sclerotherapy (P = .03). Reduction in outlet size and changes in cognitive and emotional eating behaviors were predictors of weight loss after GJAR on a univariate analysis. On a multivariate analysis, the only predictor of weight loss was a reduction in outlet size (P< .01)., Conclusions: Endoscopic suturing resulted in greater reduction in outlet size, improvement in eating behavior, and weight loss than sclerotherapy. Reduction of anastomosis size was a significant predictor of weight loss after GJAR., Competing Interests: All authors have no conflict of interest to declare, (Copyright © 2016 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

Purpose: To review the presentation, imaging, clinical management, and outcomes in patients with mycotic aneurysm (MA)., Methods: Fifty-five cases in 49 patients (33 men, 16 women, average age: 66.2years) were identified., Results: Of 49 patients, only 20% presented with the classic clinical triad of fever, elevated white count, and pain. Computed tomography was the most utilized imaging modality; focal vascular outpouching was the most frequent imaging finding (76%). There was 17% mortality rate within 6months of diagnosis despite intervention., Conclusions: Clinical presentation and blood cultures can be nonspecific, highlighting the importance of imaging diagnosis of MA to expedite treatment., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Mycotic aneurysm (MA) is a focal dilation of an infected arterial wall. This uncommon disease follows an aggressive, unpredictable clinical course with significant mortality and presents unique diagnostic and therapeutic challenges. This review discusses the pathogenesis and the diagnostic challenges of MA., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Oligometastatic prostate cancer has increasingly been recognized as a unique clinical state with therapeutic implications. It has been proposed that patients with oligometastases may have a more indolent course and that outcome may be further improved with metastasis-directed local ablative therapy. In addition, there are differing schools of thoughts regarding whether oligometastases represent isolated lesions-where targeted therapy may render a patient disease free-or whether they coexist with micrometastases, where targeted therapy in addition to systemic therapy is required for maximal clinical impact. As such, the approach to the patient with oligometastatic prostate cancer requires multidisciplinary consideration, with surgery, radiotherapy, and systemic therapy potentially of benefit either singularly or in combination. Indeed, mounting evidence suggests durable disease-free intervals and, in some cases, possibly cure, may be achieved with such a multimodal strategy. However, selecting patients that may benefit most from treatment of oligometastases is an ongoing challenge. Moreover, with the advent of new, highly sensitive imaging technologies, the spectrum based on CT of the abdomen and pelvis and technetium bone scan of localized to oligometastatic to widespread disease has become increasingly blurred. As such, new MRI- and PET-based modalities require validation. As some clinical guidelines advise against routine prostate-specific antigen screening, the possibility of more men presenting with locally advanced or de novo oligometastatic prostate cancer exists; thus, knowing how best to treat these patients may become more relevant at a population level. Ultimately, the arrival of prospective clinical data and better understanding of biology will hopefully further inform how best to treat men with this disease.

Unlabelled: Morbid obesity is a risk factor for numerous diseases including liver disease with an incidence of hepatic steatosis from 70 to 80%. Although surgical treatment is effective in reducing weight, its effects on the liver have not been established convincingly. We report 2 cases of patients with bariatric surgery and who had a fulminant hepatic failure resulting in death., Methods: case N.º 1: a 36-year-obesity intervened in 1995 with VBG with BMI 52.5 to reganancia weight back after revision surgery is performed in 2009 performed distal gastric bypass. Case N.º 2: 42 Woman surgery for obesity in 2009 by distal gastric bypass with a BMI of 51 and placement of prophylactic Composix kugel midline mesh. After 3 years with good weight loss, presents abscess wall and enterocutaneous fistula he was surgically intervene. extracting mesh, identifying themselves two fistulas in alimentary and common intestinals loops that are removed and new anastomosis was performed., Results: case N.º 1: at 2 months of revision surgery, tje patient starts vomiting secondary to stenosis of gastrojejunostomy anastomosis and symptoms of progressive jaundice, ascites and encephalopathy fulminant hepatic failure resulting in death. Case N.º 2: in the immediate postoperative period starts increased drainage of debit and rise of liver enzymes cytolysis and coagulopathy. It reinterviene on suspicion of anastomotic leak and abdominal Sepsis, developing fulminant hepatic failure with coagulopathy and encephalopathy is treated by MARS system, and died within 4 hours of the onset of therapy., Conclusions: although current surgical techniques of bariatric surgery are considered quite safe, there have been cases of hepatic failure, unclear whether this would relate to the progression of a preexisting steatohepatitis, or may have other predisposing factors related to surgery. Treatments available, the emergency orthotopic liver transplantation is one of the best interventions. For our patients the outcome was fatal triggering the death of both. In both cases presented a septic shock with positive ascitic fluid cultures to multiresistant microorganisms, and both had revision surgery. Unfortunately the factors that can influence that occur after bariatric surgery such complications, and probably will be grounds for future studies are unknown., (Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.)

Objective: To determine whether early environmental factors, such as cesarean delivery, breastfeeding, and exposure to smoking or herpes viruses, are associated with neuromyelitis optica (NMO) risk in children., Methods: This is a case-control study of pediatric NMO, multiple sclerosis (MS), and healthy subjects. Early-life exposures were obtained by standardized questionnaire. Epstein-Barr virus, cytomegalovirus, and herpes simplex virus 1 antibody responses were determined by ELISA. Multivariate logistic regression models were used to adjust for age at sampling, sex, race, and ethnicity., Results: Early-life exposures were obtained from 36 pediatric subjects with NMO, 491 with MS, and 224 healthy controls. Daycare (odds ratio [OR] 0.33, 95% confidence interval [CI] 0.14, 0.78; p < 0.01) and breastfeeding (OR 0.42, 95% CI 0.18, 0.99; p = 0.05) were associated with lower odds of having NMO compared with healthy subjects. Cesarean delivery tended to be associated with 2-fold-higher odds of NMO compared with having MS/clinically isolated syndrome (OR 1.98, 95% CI 0.88, 4.59; p = 0.12) or with being healthy (OR 1.95, 95% CI 0.81, 4.71; p = 0.14). Sera and DNA were available for 31 subjects with NMO, 189 with MS, and 94 healthy controls. Epstein-Barr virus, herpes simplex virus 1, cytomegalovirus exposure, and being HLA-DRB1*15 positive were not associated with odds of having NMO compared with healthy subjects., Conclusions: Exposure to other young children may be an early protective factor against the development of NMO, as previously reported for MS, consistent with the hypothesis that infections contribute to disease risk modification. Unlike MS, pediatric NMO does not appear to be associated with exposures to common herpes viruses., (© 2014 American Academy of Neurology.)

Nonischemic myocardial disease or cardiomyopathy can present as arrhythmia, palpitations, heart failure, dyspnea, lower extremity edema, ascites, syncope, and/or chest discomfort and can be classified as either systolic, diastolic, or a combination of both. Echocardiography is the mainstay of evaluating left ventricular function. However, cardiac magnetic resonance imaging (MRI) is now considered the reference standard imaging technique to assess myocardial anatomy, function, and viability. Advanced MRI techniques with delayed myocardial enhancement, especially, can provide information beyond echocardiography for tissue characterization in CM and can assist in determining specific etiology or in narrowing the differential. Often imaging enhancement patterns, signal characteristics, and morphology on MRI can lead to specific diagnoses such as amyloidosis, hypertrophic CM, or iron deposition. Cardiac computed tomography is usually used in excluding coronary artery disease but can also be used in some patients unable to undergo cardiac MRI to assess arrhythmogenic right ventricular dysplasia. Both 18-F-fluoro-2-deoxyglucose positron emission tomography and delayed contrast-enhanced MRI can be used to assess for cardiac sarcoidosis. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 3 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.

Objectives: To determine the prevalence of major comorbidities of morbidity obese patients and to evaluate the gastric bypass effect on the weight status, cardiovascular risk and quality of life in these patients., Methods: The evolution of weight, comorbidity, 10- year follow-up of cardiovascular risk (estimated by the Framingham risk score) and quality of life using the test BAROS (Bariatric Analysis and Reporting Outcome System) was analyzed in 162 patients with morbid obesity before and 2 years after gastric bypass., Results: Body mass index (BMI) was reduced from 51.12 ± 7.22 to 29.94 ± 4.86 kg/m2 (72.85% loss of excess weight). Hypertension (HT), dyslipidemia and type 2 diabetes mellitus (T2DM) were resolved in 71.93%, 91.38% and 82.93% respectively (p < 0.001). Cardiovascular risk greater than 10% was reduced from 25.91% to 4.32% (p < 0.001). According to BAROS scale, surgery was positive in 95% of cases., Conclusions: Gastric bypass is very effective in weight loss; benefits in comorbidities, cardiovascular risk and quality of life., (Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.)

Potato leafroll virus (PLRV) encodes two capsid proteins, major protein (CP) and minor protein (P5), an extended version of the CP produced by occasional translational 'readthrough' of the CP gene. Immunogold electron microscopy showed that PLRV CP is located in the cytoplasm and also localized in the nucleus, preferentially targeting the nucleolus. The nucleolar localization of PLRV CP was also confirmed when it was expressed as a fusion with green fluorescent protein (GFP) via an Agrobacterium vector. Mutational analysis identified a particular sequence within PLRV CP involved in nucleolar targeting [the nucleolar localization signal (NoLS)]. Minor protein P5 also contains the same NoLS, and was targeted to the nucleolus when it was expressed as a fusion with GFP from Agrobacterium. However, P5-GFP lost its nucleolar localization in the presence of replicating PLRV.

Strong RNA silencing was induced in plants transformed with an amplicon consisting of full-length cDNA of potato leafroll virus (PLRV) expressing green fluorescent protein (GFP), as shown by low levels of PLRV-GFP accumulation, lack of symptoms and accumulation of amplicon-specific short interfering RNAs (siRNAs). Inoculation of these plants with various viruses known to encode silencing suppressor proteins induced a striking synergistic effect leading to the enhanced accumulation of PLRV-GFP, suggesting that it had escaped from silencing. However, PLRV-GFP escape also occurred following inoculation with viruses that do not encode known silencing suppressors and treatment of silenced plants with biotic or abiotic stress agents. We propose that viruses can evade host RNA-silencing defences by a previously unrecognized mechanism that may be associated with a host response to some types of abiotic stress such as heat shock.

Unlabelled: SUMMARY Taxonomy: PLRV is the type species of the genus Polerovirus, in the family Luteoviridae. Isolates are known from most continents, presumably all spread in potato material derived from the Andean region of South America. Physical properties: PLRV particles are isometric and c. 25 nm in diameter. They contain one major (c. 23 kDa) and one minor (c. 80 kDa) protein. The genome is a single 5.8 kb positive sense RNA that has neither a 5'-cap nor 3' poly(A) but carries a VPg., Host Range: PLRV has a limited host range; about 20 largely solanaceous species have been infected experimentally. PLRV is a common pathogen of potato, and closely related isolates are occasionally found in tomato, but no other crops are affected., Symptoms: Infection, especially from infected seed potato stocks, causes leafrolling and stunting, the extent depending on the potato cultivar. Biological properties: The biology of PLRV is that of a classic luteovirus. Its isometric particles are persistently transmitted by aphids in a non-propagative manner, it multiplies largely in phloem tissue and disease symptoms reflect this localization. A decade or so of molecular study has revealed the many features of PLRV that are characteristic of its family. Key attractions: In recent years some interesting features of PLRV have emerged that are the focus of further investigation. These are, its phloem confinement, its movement in infected plants, its ability to suppress gene silencing and new ideas about the structure of its particles. This review describes the background to PLRV and points towards these new developments.

From 1998 to 2001, 216 ingredients intended for incorporation into chicken feed, which included groundnut cake, maize, millets, rice bran, sorghum, soybean, sunflower, and mixed feeds, were assayed for aflatoxins and ochratoxin A contamination using an indirect competitive enzyme-linked immunosorbent assay. Thirty-eight percent of the samples were contaminated with aflatoxins and 6% with ochratoxin A. The incidence scores of aflatoxin contamination in excess of 10 microg/kg were 41 of 95 for maize, 18 of 30 for mixed feeds, 10 of 37 for groundnut, 6 of 29 for sorghum, 5 of 10 for sunflower, 3 of 14 for rice bran, and 1 of 8 for millet. Ochratoxin A contamination, in excess of 10 microg/kg, was found in 9 of 29 sorghum samples, 1 of 27 groundnut samples, 1 of 14 rice bran samples, 1 of 10 sunflower samples, and 2 of 8 millet samples. Ochratoxin A was not found in maize and mixed feeds. None of the three soybean samples contained ochratoxin A. This is the first report, to our knowledge, of co-occurrence of aflatoxins and ochratoxin A in Indian poultry feeds. The results confirm the importance of analysis of ingredients before incorporating them into mixed feeds.

Introduction: Pregnancy produces multiple changes in the mother's body, most of which have been studied. However, changes in hepatosplenic circulation are not well-known. The routine use of ultrasonography and of echo-Doppler has created new possibilities for the knowledge of splenic circulation during pregnancy., Material and Method: We studied 30 healthy pregnant women who had given their informed consent. To evaluate the morphological and hemodynamic changes that might occur in the splenic vessels during pregnancy and immediate puerperium, laboratory investigations, obstetric and hepatic ultrasonography, and hepatosplenic echo-Doppler were performed between weeks 8-12, 20-24, and 32-36, as well as in the immediate puerperium., Results: The caliber of the vena porta and its tributaries, as well as that of its intrahepatic branches, increased while the caliber of the suprahepatic vessels slightly decreased during pregnancy. The hemodynamic changes detected by Doppler ultrasonography were: progressive flattening of the pulsed Doppler trace of the suprahepatic vessels during the course of pregnancy; a progressive reduction in mean portal velocity, which was more marked in the third trimester, and a decrease in the markers of resistance in the hepatic artery and superior mesenteric artery., Conclusions: Hemodynamic changes in hepatosplenic circulation are produced during pregnancy that can be safely and effectively evaluated in real time by ultrasonography and echo-Doppler. Knowledge of these changes is required to evaluate these vessels in pathological conditions.

High-titer rabbit polyclonal antibodies to aflatoxin M(1) (AFM1) were produced by utilizing AFM1-bovine serum albumin (BSA) conjugate as an immunogen. An indirect competitive enzyme-linked immunosorbent assay was standardized for estimating AFM1 in milk and milk products. To avoid the influence of interfering substances present in the milk samples, it was necessary to prepare AFM1 standards in methanol extracts of certified reference material (CRM) not containing detectable AFM1 (< 0.05 ng/g). The reliability of the procedure was assessed by using CRM with AFM1 concentrations of < 0.5 and 0.76 ng/g. Also, assays of milk samples mixed with AFM1 ranging in concentration between 0.5 and 50 ng/L gave recoveries of > 93%. The relative cross-reactivity with aflatoxins (AF) and ochratoxin A, assessed as the amount of AFM1 necessary to cause 50% inhibition of binding, was 5% for AFB1 and much less for AFB2, AFG1, and AFG2; there was no reaction with ochratoxin A. AFM1 contamination was measured in retail milk and milk products collected from rural and periurban areas in Andhra Pradesh, India. Of 280 milk samples tested, 146 were found to contain < 0.5 ng/mL of AFM1; in 80 samples it varied from 0.6 to 15 ng/mL, in 42 samples from 16 to 30 ng/mL, and in 12 samples from 31 to 48 ng/mL. Most of the milk samples that contained high AFM1 concentrations were obtained from periurban locations. The results revealed a significant exposure of humans to AFM1 levels in India and thus highlight the need for awareness of risk among milk producers and consumers.

A virus disease of peanut (groundnut, Arachis hypogaea L.), characterized by necrosis of the stem and terminal leaflets followed by death, caused severe crop losses in Andhra Pradesh, India during the rainy season of the year 2000. The disease was referred to as peanut stem necrosis disease (PSND). Cowpea (Vigna unguiculata, cv. C-152) and Phaseolus vulgaris (cv. Topcrop) were found to be suitable for propagating the virus. In laboratory inoculation tests, the virus was found to infect a large number of plants. In laboratory tests, the virus was transmitted by the thrips Frankliniella schultzei. Virus particles were purified by differential centrifugation and sucrose density gradient centrifugation from infected cowpea plants and were used to elicit the production of a rabbit polyclonal antiserum with high titer. Extracts of infected plants reacted with antiserum to Tobacco streak virus (TSV). Analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of proteins extracted from purified virus particles showed them to contain a major protein of 28 kDa and a minor, though prominent, protein of 57 kDa. Gel electrophoresis of RNA extracted from virus particles resolved it into four species with estimated sizes of 3.7, 3.1, 2.2, and 0.9 kb. Complementary DNA (cDNA) was made using as template a sample of the 2.2-kb RNA 3 and as primer an oligonucleotide complementary to sequence in RNA 3 of TSV. Following second strand synthesis, the cDNA was cloned in pBluescript and the nucleotide sequence was obtained for 868 nt of the cDNA. The sequence was 88.4% identical to the sequence in RNA 3 of TSV (strain WC). The results indicate that the causal agent of PSND is TSV. The same virus also was found to cause sunflower necrosis, an economically important disease in India. Studies on the epidemiology of PSND and the identification of virus-resistant peanut genotypes have been initiated to devise strategies to control PSND.

In plants infected with Potato leafroll virus (PLRV), or other luteoviruses, infection is very largely confined to cells in the vascular system. Even in tobacco plants transformed with PLRV full-length cDNA, in which all mesophyll cells should synthesize infectious PLRV RNA transcripts, only a minority of the mesophyll cells accumulate detectable amounts of virus. We have explored this phenomenon further by transforming a better PLRV host, Nicotiana benthamiana, with the same transgene, by superinfecting transformed plants with Potato virus Y and by producing tobacco plants in which cells contained both PLRV cDNA and DNA encoding the P1/HC-Pro genes of the potyvirus Tobacco etch virus. A greater proportion of cells in superinfected plants or in doubly transgenic plants accumulated PLRV than did in singly transgenic tobacco plants. However, most cells in these plants did not accumulate virus. To investigate restriction of the multiplication of viruses containing PLRV sequences, transgenic plants were infected with a chimeric virus that consisted of Tobacco mosaic virus (TMV) containing genes for either the coat protein (CP) of PLRV or jellyfish green fluorescent protein (GFP) in place of the TMV coat protein. The virus that encoded PLRV CP spread more slowly and accumulated less extensively than did the virus that expressed GFP. The results support the suggestion that an RNA-mediated form of resistance that resembles post-transcriptional gene silencing operates in non-vascular cells and may be part of the mechanism that restricts PLRV to vascular tissue in conventionally infected plants.

Ochratoxin A (OA) contamination of black pepper, coriander seeds, powdered ginger and turmeric powder was estimated using indirect competitive ELISA. Samples (1 g) were extracted with 0.5% potassium chloride (KCl) in 70% methanol (5 ml) and diluted subsequently to give two-fold to ten-fold step-wise dilutions in phosphate-buffered saline containing 0.05% Tween 20 and 0.2% bovine serum albumin (PBS-T BSA). For extracts from the spices analysed, ELISA estimates of OA concentrations were compared with those made by HPLC. All estimates were within 1-2 standard deviation of the ELISA values. More than 90% of OA added to spice samples was recovered from samples containing between 5 and 100 microg/kg OA. Extracts of OA-free spice samples contained substances that interfered with ELISA, presumably because of non-specific reactions. This effect was avoided by preparing all the test solutions in extracts of OA-free spice samples. In 126 samples obtained from retail shops, OA was found to exceed 10 microg/kg in 14 (in the range of 15-69 microg/kg) of 26 black pepper samples, 20 (in the range of 10-51 microg/kg) of 50 coriander samples, two (23 microg/kg and 80 microg/kg) of 25 ginger samples and nine (in the range of 11-102 microg/kg) of 25 turmeric samples. This is the first record in India of the occurrence of OA in what are some of the most widely used spices in Indian cooking.

Potato leafroll virus (PLRV) was mechanically transmissible when inocula also contained the umbravirus Pea enation mosaic virus-2 (PEMV-2). In plants infected with PLRV and PEMV-2, PLRV accumulated in clusters of mesophyll cells in both inoculated and systemically infected leaves. No transmissions were obtained by coinoculation with Potato virus Y, Potato virus X (PVX), Tobacco mosaic virus, or Cucumber mosaic virus (CMV), although PLRV was transmissible from mixtures with CMV(ORF4) (a recombinant that contained the movement protein (MP) gene of the umbravirus Groundnut rosette virus (GRV) in place of the CMV MP gene). In contrast, neither a recombinant PVX that expressed GRV MP nor a mutant of CMV(ORF4), in which the CMV 2b gene was untranslatable, was able to help PLRV transmission. Possibly both a cell-to-cell movement function and counterdefense mechanisms such as those that block posttranscriptional gene silencing are involved in movement of PLRV within plants and its mechanical transmission between plants., (Copyright 2001 Academic Press.)

Aims: To test phage-displayed random peptide libraries as sources of peptides that mimic the binding of aflatoxin B1 to monoclonal antibodies raised against the toxin., Methods and Results: For two of the three MAbs tested, clones were obtained by panning, producing phage that bound specifically to MAb 13D1-1D9 (MAb 24; specific for aflatoxins B1 and G1) and MAb 6E12-1E9 (MAb 13; specific for aflatoxins B1, G1 and B2) in ELISA. The amino acid sequences of the binding peptides varied. Those binding to MAb 24 contained the sequence of '...YMD...', and those that bound to MAb 13 contained the dipeptide 'PW'. Mimotope phage was used in a competition ELISA format for assaying aflatoxin concentrations., Conclusion: The results show that mimotope preparations are effective substitutes for pure toxin in these ELISA procedures., Significance and Impact of the Study: These results should contribute significantly to enhancing the safety and diminishing the costs of aflatoxin assays.

ABSTRACT Lepidopteran cells (Spodoptera frugiperda) produced isometric virus-like particles (VLP) when infected with a recombinant baculovirus Ac61 that contained the Potato leafroll virus (PLRV) coat protein gene modified with an N-terminal histidine tag (P3-6H). Cells infected with AcFL, a recombinant baculovirus that expressed cDNA copies of the PLRV genome RNA, did not produce virus-like particles (VLP). In cell lines doubly infected with Ac61 and AcFL, VLP were formed that contained PLRV-RNA packaged in P3-6H coat protein (FL). Both the P3-6H and the FL particles were morphologically indistinguishable from particles of PLRV despite the fact that they lacked the P5 readthrough protein present in wild-type PLRV. When aphids (Myzus persicae) were fed on, or injected with, purified PLRV, or VLP of either type (FL or P3-6H) and examined by electron microscopy, no differences were observed among treatments for particle endocytosis, transcellular transport, or exocytosis at the aphid midgut or accessory salivary glands. Particles were observed in the salivary canals and in the salivary duct leading out of the aphid. These results suggest that P5 readthrough protein of PLRV may not be essential for cellular transport of virus through aphid vectors.

Polyclonal antibodies were produced for Ochratoxin A (OA) by injecting OA-bovine serum albumin (BSA) conjugate subcutaneously at multiple sites into a New Zealand White inbred rabbit. Antiserum could be used at a dilution exceeding 1:100 000 in an indirect competitive enzyme-linked immunosorbent assay (ELISA), and detected OA concentrations up to 0.1 ng/mL. The 50% inhibition binding (I(50)) of OA was 5 ng/mL. Antibodies did not react with ochratoxin B, coumarin, 4-hydroxycoumarin, L-phenylalanine, and aflatoxin B1. OA contamination in chilies (Capsicum annum L.) collected from commercial markets and cold storage units was determined. The mean recoveries from OA-free chilies spiked with 1 to100 microg of OA per kg of chili sample were 90-110% with a standard deviation of <10%. Of 100 chili samples tested, 26 were found to contain over 10 microg/kg of OA. In 12 samples the OA concentration varied from 10 to 30 microg/kg, in 10 samples from 30 to 50 microg/kg, in 3 samples from 50 to100 microg/kg, and in one sample it was 120 microg/kg. This is the first record in India of OA in chilies, a major component of cooked foods in this country, and it is noteworthy that OA contamination exceeded the permissible limit for human consumption of less than 20 microg/kg in over 26% of the market samples tested.

A full-length cDNA corresponding to the RNA genome of Potato leafroll virus (PLRV) was modified by inserting cDNA that encoded the jellyfish green fluorescent protein (GFP) into the P5 gene near its 3' end. Nicotiana benthamiana protoplasts electroporated with plasmid DNA containing this cDNA behind the 35S RNA promoter of Cauliflower mosaic virus became infected with the recombinant virus (PLRV-GFP). Up to 5% of transfected protoplasts showed GFP-specific fluorescence. Progeny virus particles were morphologically indistinguishable from those of wild-type PLRV but, unlike PLRV particles, they bound to grids coated with antibodies to GFP. Aphids fed on extracts of these protoplasts transmitted PLRV-GFP to test plants, as shown by specific fluorescence in some vascular tissue and epidermal cells and subsequent systemic infection. In plants agroinfected with PLRV-GFP cDNA in pBIN19, some cells became fluorescent and systemic infections developed. However, after either type of inoculation, fluorescence was mostly restricted to single cells and the only PLRV genome detected in systemically infected tissues lacked some or all of the inserted GFP cDNA, apparently because of naturally occurring deletions. Thus, intact PLRV-GFP was unable to move from cell to cell. Nevertheless, PLRV-GFP has novel potential for exploring the initial stages of PLRV infection.

The RNA-2 molecule of an isolate of the L serotype of Indian peanut clump virus (IPCV) was shown to consist of 4,290 nucleotides with five open reading frames (ORF). The arrangement of the ORFs resembled that in RNA-2 of Peanut clump virus (PCV) from West Africa. The proteins encoded by the ORFs in IPCV-L RNA are between 32% and 93% identical to those encoded by PCV RNA. Partial sequence data for the RNA-2 of isolates of the H and T serotypes of IPCV show that the coat and P40 proteins encoded by the 5'-most ORFs of RNA-2 of IPCV-L, IPCV-H and IPCV-T are as similar to each other as any is to the corresponding proteins of PCV. A conserved motif 'F-E-x6-W' is present near the C-termini of the coat proteins of all three IPCV serotypes and of PCV, as it is in the coat proteins of other viruses that have rod-shaped particles, such as Tobacco mosaic virus and Tobacco rattle virus. The results support the distinction of IPCV and PCV as separate virus species, but also raise the question of how the serotypes of IPCV should be classified.