Search

ABSTRACT: Objectives: Bebtelovimab is an anti-SARS-CoV-2 monoclonal antibody active against Omicron lineage variants authorized to treat high-risk outpatients with COVID-19. We sought to determine the real-world effectiveness of bebtelovimab during the Omicron phases BA.2/BA2.12.1/BA4/BA5. Methods: We conducted a retrospective cohort study of adults with SARS-CoV-2 infection between April 6 and October 11, 2022, using health records linked to vaccine and mortality data. We used propensity scores to match of bebtelovimab-treated with untreated outpatients. The primary outcome was 28-day all-cause hospitalization. The secondary outcomes were 28-day COVID-19-related hospitalization, 28-day all-cause mortality, 28-day emergency department visits, maximum respiratory support level, intensive care unit admission, and in-hospital mortality among hospitalized patients. We used logistic regression to determine bebtelovimab treatment effectiveness. Results: Among 22,720 patients with SARS-COV-2 infection, 3739 bebtelovimab-treated patients were matched to 5423 untreated patients. Compared with no treatment, bebtelovimab was associated with lower odds of 28-day all-cause hospitalization (1.3% vs 2.1%, adjusted odds ratio: 0.53; 95% confidence interval: 0.37-0.74, P

ABSTRACT: Objectives: Sotrovimab effectively prevented progression to severe disease and mortality following infection with pre-Omicron SARS-CoV-2 variants. We sought to determine whether sotrovimab is similarly effective against SARS-CoV-2 Omicron variant infection. Methods: Observational cohort study of non-hospitalized adult patients with SARS-CoV-2 infection from December 26, 2021, to March 10, 2022, using electronic health records from a statewide health system. We propensity-matched patients not receiving authorized treatment for each patient treated with sotrovimab. The primary outcome was 28-day hospitalization; secondary outcomes included mortality. We also propensity-matched sotrovimab-treated patients from the Omicron and Delta phases. Logistic regression was used to determine sotrovimab effectiveness during Omicron and between variant phases. Results: Of 30,247 SARS-CoV-2 Omicron variant infected outpatients, we matched 1542 receiving sotrovimab to 3663 not receiving treatment. Sotrovimab treatment was not associated with reduced odds of 28-day hospitalization (2.5% vs 3.2%; adjusted odds ratio [OR] 0.82, 95% CI 0.55, 1.19) or mortality (0.1% vs 0.2%; adjusted OR 0.62, 95% CI 0.07, 2.78). Between phases, the observed treatment OR was higher during Omicron than during Delta (OR 0.85 vs 0.39, respectively; interaction P-value = 0.053). Conclusion: Real-world evidence demonstrated that sotrovimab was not associated with reduced 28-day hospitalization or mortality among COVID-19 outpatients during the Omicron BA.1 phase.

We report on a Mexican mestizo with a multisystemic syndrome including neurological involvement and a type I serum transferrin isoelectric focusing (Tf IEF) pattern. Diagnosis of PMM2-CDG was obtained by clinical exome sequencing (CES) that revealed compound heterozygous variants in PMM2, the encoding gene for the phosphomannomutase 2 (PMM2). This enzyme catalyzes the conversion of mannose-6-P to mannose-1-P required for the synthesis of GDP-Man and Dol-P-Man, donor substrates for glycosylation reactions. The identified variants were c.422G>A (R141H) and c.178G>T, the former being the most frequent PMM2 pathogenic mutation and the latter a previously uncharacterized variant restricted to the Latino population with conflicting interpretations of pathogenicity and that we here report causes leaky non-functional alternative splicing (p.V60Cfs*3).

Background: Tocilizumab has been proposed as a treatment for the new disease COVID-19, however, there is not enough scientific evidence to support this treatment. The objective of this study is to analyze whether the use of tocilizumab is associated with respiratory improvement and a shorter time to discharge in patients with COVID-19 and lung involvement. Methods: Observational study on a cohort of 418 patients, admitted to three county hospitals in Catalonia (Spain). Patients admitted consecutively were included and followed until discharge or up to 30 days of admission. A sub-cohort of patients treated with tocilizumab and a sub-cohort of control patients were identified, matched by a large number of risk factors and clinical variables. Sub-cohorts were also matched by the number of other treatments for COVID-19 that patients received. Increment in SAFI (inspired oxygen fraction / saturation) 48 h after the start of treatment, and time to discharge, were the primary outcomes. Mortality, which was a secondary outcome, was analyzed in the total cohort, by using logistic regression models, adjusted by confounders. Results: There were 96 patients treated with tocilizumab. Of them, 22 patients could be matched with an equivalent number of control patients. The increment in SAFI from baseline to 48 h of treatment, was not significantly different between groups (tocilizumab: −0.04; control: 0.09; p = 0.636). Also, no difference in time to discharge was found between the two sub-cohorts (logrank test: p = 0.472). The logistic regression models, did not show an effect of tocilizumab on mortality (OR 0.99; p = 0.990). Conclusions: We did not find a clinical benefit associated with the use tocilizumab, in terms of respiratory function at 48 h of treatment, or time to discharge.

Congenital Disorders of Glycosylation (CDG) are scarcely reported from Latin America. We here report on a Mexican mestizo with a multi-systemic syndrome including neurological involvement and a type I transferrin (Tf) isoelectric focusing (IEF) pattern. Clinical exome sequencing (CES) showed known compound missense variants in PMM2 c.422G > A (p.R141H) and c.395 T > C (p.I132T), coding for the phosphomanomutase 2 (PMM2). PMM2 catalyzes the conversion of mannose-6-P to mannose-1-P required for the synthesis of GDP-Man and Dol-P-Man, donor substrates for glycosylation reactions. This is the third reported Mexican CDG patient and the first with PMM2-CDG. PMM2 has been recently identified as one of the top 10 genes carrying pathogenic variants in a Mexican population cohort.

Background: Individuals with minor ischaemic stroke and intracranial occlusion are at increased risk of poor outcomes. Intravenous thrombolysis with tenecteplase might improve outcomes in this population. We aimed to test the superiority of intravenous tenecteplase over non-thrombolytic standard of care in patients with minor ischaemic stroke and intracranial occlusion or focal perfusion abnormality., Methods: In this multicentre, prospective, parallel group, open label with blinded outcome assessment, randomised controlled trial, adult patients (aged ≥18 years) were included at 48 hospitals in Australia, Austria, Brazil, Canada, Finland, Ireland, New Zealand, Singapore, Spain, and the UK. Eligible patients with minor acute ischaemic stroke (National Institutes of Health Stroke Scale score 0-5) and intracranial occlusion or focal perfusion abnormality were enrolled within 12 h from stroke onset. Participants were randomly assigned (1:1), using a minimal sufficient balance algorithm to intravenous tenecteplase (0·25 mg/kg) or non-thrombolytic standard of care (control). Primary outcome was a return to baseline functioning on pre-morbid modified Rankin Scale score in the intention-to-treat (ITT) population (all patients randomly assigned to a treatment group and who did not withdraw consent to participate) assessed at 90 days. Safety outcomes were reported in the ITT population and included symptomatic intracranial haemorrhage and death. This trial is registered with ClinicalTrials.gov, NCT02398656, and is closed to accrual., Findings: The trial was stopped early for futility. Between April 27, 2015, and Jan 19, 2024, 886 patients were enrolled; 369 (42%) were female and 517 (58%) were male. 454 (51%) were assigned to control and 432 (49%) to intravenous tenecteplase. The primary outcome occurred in 338 (75%) of 452 patients in the control group and 309 (72%) of 432 in the tenecteplase group (risk ratio [RR] 0·96, 95% CI 0·88-1·04, p=0·29). More patients died in the tenecteplase group (20 deaths [5%]) than in the control group (five deaths [1%]; adjusted hazard ratio 3·8; 95% CI 1·4-10·2, p=0·0085). There were eight (2%) symptomatic intracranial haemorrhages in the tenecteplase group versus two (<1%) in the control group (RR 4·2; 95% CI 0·9-19·7, p=0·059)., Interpretation: There was no benefit and possible harm from treatment with intravenous tenecteplase. Patients with minor stroke and intracranial occlusion should not be routinely treated with intravenous thrombolysis., Funding: Heart and Stroke Foundation of Canada, Canadian Institutes of Health Research, and the British Heart Foundation., Competing Interests: Declaration of interests SBC received grant funding from the Canadian Institutes of Health Research (CIHR), Heart and Stroke Foundation of Canada (HSFC), and the British Heart Foundation (BHF) to complete the TEMPO-2 study. Boehringer Ingelheim provided off-the-shelf study drug (tenecteplase) for the study. JFA has received public research grants from the Spanish Ministry of Science, the regional health department, the European Commission, and a private research grant from AstraZeneca. He has received consultant or speaker fees from Pfizer-BMS, Medtronic, and Amgen, and travel support from Daiichi-Sankyo. KSB reports speaker fees from Boehringer Ingelheim and AstraZeneca. LC has received consulting or speakers fees from Roche. JF reports speaker fees from AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Pfizer, Sankyo, and Daiichi. AG reports a grant from Microvention; speaker fees from Alexion, Biogen, and Servier Canada; and stock options for SnapDx and Collavidence. DG reports honoraria from Boehringer Ingelheim, Ipsen, and Eisai. MG reports grant funding from Medtronic and Cerenovus and consulting fees from Mentice, CSL Behring, MicroVention, and Medtronic. TSF participated in an advisory board for Roche. FL reports speaker fees and travel support from Boehringer Ingelheim. BKM has been paid honoraria from Boehringer Ingelheim and Roche. MM has received honoraria from Boehringer Ingelheim for participation at an advisory board on the approval of tenecteplase for treatment of acute ischaemic stroke. SOM has received speaker fees from Boehringer, Medtronic, Penumbra, Bayer, Pfizer, Novartis, Novo Nordisk, Servier, and Daiichi Sankyo. KWM reports grant funding from the BHF, and the Stroke Association; consultancy fees from Boehringer Ingelheim, Biogen, IschaemaView; lecture fees from Boehringer Ingelheim, IschaemaView, and Brainomix; and non-financial support (drug supply for ATTEST-2 trial) from Boehringer Ingelheim. MWP is on Boehringer Ingelheim Advisory Board for Metalyse in stroke. AP received speaker fees from Boehringer Ingelheim and travel support from AstraZeneca for attending a meeting. OMP-N has received speaker fees from Boehringer Ingelheim and AstraZeneca. RS is part funded by the UCLH Biomedical Research Centre. DS reports an unrestricted educational grant from Boehringer Ingelheim. MIW reports sponsorship or financial assistance to support attendance at scientific meetings from Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo UK, and Bayer; honoraria for lectures given at education meetings from Boehringer Ingelheim, Bristol Myers Squibb, and AstraZeneca; and payment for participation in advisory panels from Boehringer Ingelheim and Daiichi Sankyo UK. DJW is the Co-principal Investigator for Health Research Board of Ireland, Award–Improving Pathways for Acute Stroke and Rehabilitation. AYXY reports salary support from the HSFC. MDH reports grant funding from CIHR, HSFC, Alberta Innovates, and study drug from Boehringer Ingelheim; grants from NoNo and Medtronic; consulting fees from Sun Pharma Brainsgate; and a DSMB member role on many stroke clinical trials., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Introduction: In cytopathology education, Virtual Microscopy e-learning modules (VM-eLM) have achieved remarkable results in the improvement and personalization of learning. However, it remains to be determined whether these modules can significantly contribute to improving the accuracy of cytological diagnosis. The aim of this work was to create a VM-eLM for gynecologic cytopathology education designed to improve screening and interpretation skills in two groups of cytologists: experienced and nonexperienced., Materials and Methods: The module was designed in Moodle with both Whole Slide Images and Static Images taken from Papanicolaou smears that were diagnosed as: negative for intraepithelial lesion, low-grade squamous intraepithelial lesion, high-grade squamous intraepithelial lesion, squamous cell carcinoma, or adenocarcinoma. We assessed the effectiveness of the module using 1) clinical quality indicators to measure skill development and 2) a user survey., Results: After training, participants significantly improved their cytological screening skills, decreasing their false negative diagnosis by 78% in the non-experienced group and eliminating them entirely in the experienced group. Nonexperienced participants also significantly increased their recognition of low-grade squamous intraepithelial lesion and high-grade squamous intraepithelial lesion by 31% and 50%, respectively. Participants positively evaluated the module, highlighting its novelty, the possibility to train remotely, the immediate feedback and the quality of the Whole Slide Images., Conclusions: We designed, implemented and tested a VM-eLM for Gynecologic Cytopathology Education that improved cytological screening skills for both non-experienced and experienced cytologists, also increasing the diagnostic accuracy of preinvasive lesions by less experienced cytologists. The module was positively evaluated by participants, who perceived an improvement in their interpretive skills., (Copyright © 2023 American Society of Cytopathology. Published by Elsevier Inc. All rights reserved.)

Different monitoring and control policies have been implemented in schools to minimize the spread of SARS-CoV-2. Transmission in schools has been hard to quantify due to the large proportion of asymptomatic carriers in young individuals. We applied a Bayesian approach to reconstruct the transmission chains between 284 SARS-CoV-2 infections ascertained during 87 school outbreak investigations conducted between March and April 2021 in Italy. Under the policy of reactive quarantines, we found that 42.5% (95%CrI: 29.5-54.3%) of infections among school attendees were caused by school contacts. The mean number of secondary cases infected at school by a positive individual during in-person education was estimated to be 0.33 (95%CrI: 0.23-0.43), with marked heterogeneity across individuals. Specifically, we estimated that only 26.0% (95%CrI: 17.6-34.1%) of students and school personnel who tested positive during in-person education caused at least one secondary infection at school. Positive individuals who attended school for at least 6 days before being isolated or quarantined infected on average 0.49 (95%CrI: 0.14-0.83) secondary cases. Our findings provide quantitative insights on the contribution of school transmission to the spread of SARS-CoV-2 in young individuals. Identifying positive cases within 5 days after exposure to their infector could reduce onward transmission at school by at least 30%., Competing Interests: Declaration of Competing Interest MA has received research funding from Seqirus. The funding is not related to COVID-19. All other authors declare no competing interest., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Fentanyl- and methamphetamine-based counterfeit prescription drugs have driven escalating overdose death rates in the US, however their presence in Mexico has not been assessed. Our ethnographic team has conducted longitudinal research focused on illicit drug markets in Northern Mexico since 2018. In 2021-2022, study participants described the arrival of new, unusually potent tablets sold as ostensibly controlled substances, without a prescription, directly from pharmacies that cater to US tourists., Aims: To characterize the availability of counterfeit and authentic controlled substances at pharmacies in Northern Mexico available to English-speaking tourists without a prescription., Methods: We employed an iterative, exploratory, mixed methods design. Longitudinal ethnographic data was used to characterize tourist-oriented micro-neighborhoods and guide the selection of n=40 pharmacies in n=4 cities in Northern Mexico. In each pharmacy, samples of "oxycodone", "Xanax", and "Adderall" were sought as single pills, during English-language encounters, after which detailed ethnographic accounts were recorded. We employed immunoassay-based testing strips to check each pill for the presence of fentanyls, benzodiazepines, amphetamines, and methamphetamines. We used Fourier-Transform Infrared Spectroscopy to further characterize drug contents., Results: Of n=40 pharmacies, one or more of the requested controlled substances could be obtained with no prescription (as single pills or in bottles) at 28 (70.0%) and as single pills at 19 (47.5%). Counterfeit pills were obtained at 11 pharmacies (27.5%). Of n=45 samples sold as one-off controlled substances, 18 were counterfeit. 7 of 11 (63.6%) samples sold as "Adderall" contained methamphetamine, 8 of 27 (29.6%) samples sold as "Oxycodone" contained fentanyl, and 3 "Oxycodone" samples contained heroin. Pharmacies providing counterfeit drugs were uniformly located in tourist-serving micro-neighborhoods, and generally featured English-language advertisements for erectile dysfunction medications and "painkillers". Pharmacy employees occasionally expressed concern about overdose risk and provided harm reduction guidance., Discussion: The availability of fentanyl-, heroin-, and methamphetamine-based counterfeit medications in tourist-oriented independent pharmacies in Northern Mexico represents a public health risk, and occurs in the context of 1) the normalization of medical tourism as a response to rising unaffordability of healthcare in the US, 2) plummeting rates of opioid prescription in the US, affecting both chronic pain patients and the availability of legitimate pharmaceuticals on the unregulated market, 3) the rise of fentanyl-based counterfeit opioids as a key driver of the fourth, and deadliest-to-date, wave of the opioid crisis. It was not possible to distinguish counterfeit medications based on appearance of pills or geography of pharmacies, because identically-appearing authentic and counterfeit versions were often sold in close geographic proximity. Nevertheless, people who consume drugs may be more trusting of controlled substances purchased directly from pharmacies. Due to Mexico's limited opioid overdose surveillance infrastructure, the current death rate from these substances remains unknown., Competing Interests: Declaration of Competing Interest Authors declare to disclosures or competing interests., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Relevant reviews highlight the association between dysfunctional mitochondria and inflammation, but few studies address the contribution of mitochondria and mitochondria-endoplasmic reticulum (ER) contact sites (MERCs) to cellular homeostasis and inflammatory signaling. The present review outlines the important role of mitochondria in cellular homeostasis and how dysfunctional mitochondrion can release and misplace mitochondrial components (cardiolipin, mitochondrial DNA (mtDNA), and mitochondrial formylated peptides) through multiple mechanisms. These components can act as damage-associated molecular patterns (DAMPs) and induce an inflammatory response via pattern recognition receptors (PRRs). Accumulation of damaged ROS-generating mitochondria, accompanied by the release of mitochondrial DAMPs, can activate PRRs such as the NLRP3 inflammasome, TLR9, cGAS/STING, and ZBP1. This process would explain the chronic inflammation that is observed in autoimmune diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), type I diabetes (T1D), and Sjögren's syndrome. This review also provides a comprehensive overview of the importance of MERCs to mitochondrial function and morphology, cellular homeostasis, and the inflammatory response. MERCs play an important role in calcium homeostasis by mediating the transfer of calcium from the ER to the mitochondria and thereby facilitating the production of ATP. They also contribute to the synthesis and transfer of phospholipids, protein folding in the ER, mitochondrial fission, mitochondrial fusion, initiation of autophagosome formation, regulation of cell death/survival signaling, and regulation of immune responses. Therefore, alterations within MERCs could increase inflammatory signaling, modulate ER stress responses, cell homeostasis, and ultimately, the cell fate. This study shows severe ultrastructural alterations of mitochondria in salivary gland cells from Sjögren's syndrome patients for the first time, which could trigger alterations in cellular bioenergetics. This finding could explain symptoms such as fatigue and malfunction of the salivary glands in Sjögren's syndrome patients, which would contribute to the chronic inflammatory pathology of the disease. However, this is only a first step in solving this complex puzzle, and several other important factors such as changes in mitochondrial morphology, functionality, and their important contacts with other organelles require further in-depth study. Future work should focus on detecting the key milestones that are related to inflammation in patients with autoimmune diseases, such as Sjögren´s syndrome., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Dietary misreporting is the main limitation of dietary assessments and has been associated with BMI during youth. However there are no prior studies assessing misreporting and cardiometabolic risks (CMRs) in adolescence., Objectives: To examine the associations between dietary misreporting and CMR factors in adolescents and to assess the potential bias in the association between CMR and energy intake (EI) driven by dietary misreporting., Methods: Two 24-hour dietary recalls were obtained from 1512 European adolescents (54.8% girls) aged 12.5-17.5 years. Physical activity was measured by accelerometry. Cut-offs suggested by Huang were applied to identify misreporters. Height, waist circumference (WC), the sum of 4 skinfold thicknesses, diastolic blood pressure (DBP), systolic blood pressure (SBP), and cardiorespiratory fitness (CRF) measurements were taken and serum triglycerides and total-/high-density lipoprotein cholesterol ratio were analyzed. A sex- and age-specific clustered CMR score (n = 364) was computed. Associations were investigated by multilevel regression analyses adjusting for age, sex, center, socioeconomic status, and physical activity., Results: Underreporting (24.8% adolescents) was significantly (P < 0.05) associated with a higher WC, waist-to-height ratio (WHeR), and sum of skinfold thickness, whereas overreporting (23.4% adolescents) was significantly associated with a lower WC, WHeR, sum of skinfold thickness, and SBP. Associations between CMR factors and EI were significantly affected by misreporting, considering various approaches. Significant, positive associations became inverse after adjusting for misreporting for WC and WHeR. The opposite was true for the sum of skinfold thickness, SBP, and CMR score. The associations between EI and DBP and CRF did not remain significant after adjusting for misreporting., Conclusions: CMR factors differed among misreporting groups, and both abdominal and total fat mass indicators were more strongly associated with all forms of misreporting than was BMI. Moreover, misreporting seems to bias EI and CMR associations in adolescents. Therefore, energy misreporting should be taken into account when examining diet-CMR associations., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Background: Interstitial lung abnormalities (ILA) and interstitial lung disease (ILD) are seen in up to 60% of individuals with rheumatoid arthritis (RA), some of which will progress to have a significant impact on morbidity and mortality rates. Better characterization of progressive interstitial changes and identification of risk factors that are associated with progression may enable earlier intervention and improved outcomes., Research Question: What are baseline characteristics associated with RA-ILD progression?, Study Design and Methods: We performed a retrospective study in which all clinically indicated CT chest scans in adult individuals with RA from 2014 to 2016 were evaluated for interstitial changes, and the data were further subdivided into ILA and ILD based on clinical record review. Progression was determined visually and subsequently semiquantified., Results: Those individuals with a spectrum of interstitial changes (64 of 293) were older male smokers and less likely to be receiving biologics/small molecule disease-modifying antirheumatic drugs. Of 44% of the individuals with ILA, 46% had had chest CT scans performed for nonpulmonary indications. Of the 56 individuals with ILA/ILD with sequential CT scans, 38% had evidence of radiologic progression over 4.4 years; 29% of of individuals with ILA progressed. Risk factors for progressive ILA/ILD included a subpleural distribution and higher baseline involvement., Interpretation: Of 293 individuals with RA with clinically indicated CT scans, interstitial changes were observed in 22%, one-half of whom had had a respiratory complaint at the time of imaging; radiologic progression was seen in 38%. Of individuals with progressive ILA, one-half had had baseline CT scans performed for nonpulmonary indications. Subpleural distribution and higher baseline ILA/ILD extent were risk factors associated with progression. Prospective longitudinal studies of RA-ILA are necessary., (Copyright © 2020 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Skin-to-skin contact (SCC) at birth has a positive impact on breastfeeding indicators and physiological stabilization at birth. On the other hand, globally and in Colombia, morbidity and mortality have increased in intermediate- and low-risk infants. The aim of the study was to assess the effect of immediate skin-to-skin contact, compared to separation at birth, on the risk of hospitalization of intermediate- and low-risk infants prior to discharge from the maternity ward., Methodology: A retrospective cohort study of newborn who underwent a SCC compared to habitual management was conducted. Intermediate- and low-risk neonates with spontaneous neonatal adaptation and cardiorespiratory stability at birth were included. Main outcome measure was hospital admission prior to the discharge from the maternity ward., Result: A total of 816 infants were included, 672 (82.3%) in the skin-to-skin contact group and 144 (17.6%) in the habitual management group. The main causes of hospital admission were jaundice and feeding/sucking related issues. Significantly lower admission to the neonatal unit was found for infants in the contact group compared to infants who did not receive skin-to-skin contact (13.8% vs. 26.4%; OR 0.46, 95% CI 0.29-0.71, p = 0.001)., Conclusion: Skin-to-skin contact in newborns of intermediate and low risk has protective effects on the risk of hospital admission within the first few hours of life. SSC is proposed as a prevention strategy in second-level care scenarios., Competing Interests: Declaration of competing interest None., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: Surgical site infections (SSIs) complicate 1% to 9% of elective spine surgeries. Previously identified risk factors include diabetes mellitus type 2, obesity, and chronic kidney disease. We sought to determine whether the use of postoperative surgical site drains is associated with deep SSIs., Methods: We retrospectively identified patients operated for deep SSIs after surgery for degenerative spine pathologies between July 2016 and December 2018. Patients were excluded if the reason for operation was other than deep SSI or if their primary operation was for infection or tumor. Using their index procedure and the electronic medical record, patients were matched to controls based on age, surgical invasiveness, International Classification of Diseases, Tenth Revision, Clinical Modification code, race, and sex. Our main outcome of interest was whether drain retention time, total output, or daily output differed significantly between cases and controls., Results: We identified 38 patients who met inclusion criteria. Infected patients had a higher body mass index (34.2 vs. 29.9 kg/m 2 ; P = 0.001), higher odds of having diabetes mellitus type 2 (55.3% vs. 18.4%; P = 0.002), longer drain retention time (5.5 vs. 3.5 days; P = 0.02), and longer inpatient stay (9.5 vs. 4.3 days; P = 0.005). Multivariable logistic regression demonstrated that even after controlling for the other risk factors, drain retention time independently predicted postoperative surgical site infection (odds ratio: 1.36; P = 0.02)., Conclusions: Prolonged surgical drain retention correlates with risk of deep SSI after surgery for degenerative spine disease independent of surgical invasiveness, diabetes mellitus type 2 status, and total drain output. Our data suggest early postoperative drain removal may potentially decrease the risk of SSI and shorten duration of hospital stay., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Stroke thrombolysis with alteplase is currently recommended 0-4·5 h after stroke onset. We aimed to determine whether perfusion imaging can identify patients with salvageable brain tissue with symptoms 4·5 h or more from stroke onset or with symptoms on waking who might benefit from thrombolysis., Methods: In this systematic review and meta-analysis of individual patient data, we searched PubMed for randomised trials published in English between Jan 1, 2006, and March 1, 2019. We also reviewed the reference list of a previous systematic review of thrombolysis and searched ClinicalTrials.gov for interventional studies of ischaemic stroke. Studies of alteplase versus placebo in patients (aged ≥18 years) with ischaemic stroke treated more than 4·5 h after onset, or with wake-up stroke, who were imaged with perfusion-diffusion MRI or CT perfusion were eligible for inclusion. The primary outcome was excellent functional outcome (modified Rankin Scale [mRS] score 0-1) at 3 months, adjusted for baseline age and clinical severity. Safety outcomes were death and symptomatic intracerebral haemorrhage. We calculated odds ratios, adjusted for baseline age and National Institutes of Health Stroke Scale score, using mixed-effects logistic regression models. This study is registered with PROSPERO, number CRD42019128036., Findings: We identified three trials that met eligibility criteria: EXTEND, ECASS4-EXTEND, and EPITHET. Of the 414 patients included in the three trials, 213 (51%) were assigned to receive alteplase and 201 (49%) were assigned to receive placebo. Overall, 211 patients in the alteplase group and 199 patients in the placebo group had mRS assessment data at 3 months and thus were included in the analysis of the primary outcome. 76 (36%) of 211 patients in the alteplase group and 58 (29%) of 199 patients in the placebo group had achieved excellent functional outcome at 3 months (adjusted odds ratio [OR] 1·86, 95% CI 1·15-2·99, p=0·011). Symptomatic intracerebral haemorrhage was more common in the alteplase group than the placebo group (ten [5%] of 213 patients vs one [<1%] of 201 patients in the placebo group; adjusted OR 9·7, 95% CI 1·23-76·55, p=0·031). 29 (14%) of 213 patients in the alteplase group and 18 (9%) of 201 patients in the placebo group died (adjusted OR 1·55, 0·81-2·96, p=0·66)., Interpretation: Patients with ischaemic stroke 4·5-9 h from stroke onset or wake-up stroke with salvageable brain tissue who were treated with alteplase achieved better functional outcomes than did patients given placebo. The rate of symptomatic intracerebral haemorrhage was higher with alteplase, but this increase did not negate the overall net benefit of thrombolysis., Funding: None., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background and Aims: Statin pretreatment (SP) is associated with improved outcomes in acute ischemic stroke (AIS) patients. Collateral circulation status and final infarct volume (FIV) are independent predictors of functional outcome in AIS., Methods: We sought to evaluate the association of SP with collateral circulation and FIV in AIS patients. We used a random-effects model for all the analyses, and pooled standardized mean differences (SMDs) and odds ratios (OR) on the FIV and collateral status according to SP history, respectively., Results: We identified 9 eligible studies (1186 AIS patients). History of SP was associated with lower FIV (SMD = 0.25, 95%CI: 0.07-0.42, p = 0.005) compared to negative history of SP. A trend towards good collateral scores was observed in the SP group (OR = 1.45; 95% CI, 0.92-2.29, p = 0.11). Subgroup analysis demonstrated reduced FIV among atherosclerotic stroke patients with history of SP (SMD = 0.49; 95% CI, 0.19-0.80, p = 0.001)., Conclusions: SP appears to be associated with decreased FIV, especially in atherosclerotic AIS., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Bacterial cellulose (BC) was produced by Komagataeibacter medellinensis using Hestrin and Schramm modified medium in the presence of alternative energy sources (AES), such as ethanol and acetic acid, to explore the effect of AES on the characteristics and properties of the resulting BC. In this study, the physicochemical and structural characteristics of the obtained BC were determined using Fourier-transform infrared spectroscopy, X-ray diffraction spectrometry, thermogravimetric analysis, and mechanical testing analysis. Ethanol and acetic acid (at 0.1 wt%) were proven to improve the BC yield by K. medellinensis by 279% and 222%, respectively. However, the crystallinity index (%), the degree of polymerization, and maximum rate of degradation temperatures decreased by 9.2%, 36%, and 4.96%, respectively, by the addition of ethanol and by 7.2%, 27%, and 4.21%, respectively, by the addition of acetic acid. The significance of this work, lies on the fact that there is not any report about how BC properties change when substances like ethanol or acetic acid are added to culture medium, and which is the mechanism that provokes those changes, that in our case we could demonstrate the relationship of a higher BC production rate (provoked by ethanol and acetic acid adding) and changes in BC properties., (Copyright © 2018 Elsevier B.V. All rights reserved.)

For many years, researchers in the field of autoimmunity have focused on the role of the immune components in the etiopathogenesis of autoimmune diseases. However, some studies have demonstrated the importance of target tissues in their pathogenesis and the breach of immune tolerance. The immune system as well as target tissue cells (plasmatic, β-pancreatic, fibroblast-like synoviocytes, thyroid follicular and epithelial cells of the lachrymal glands, salivary glands, intestine, bronchioles and renal tubules) share the characteristic of secretory cells with an extended endoplasmic reticulum (ER). The function of these cells depends considerably on a normal ER function and calcium homeostasis, so they can produce and secrete their main components, which include glycoproteins involved in antigenic presentation such as major histocompatibility complex (MHC) class I and II. All these proteins are synthesized and modified in the ER, and for this reason disturbances in the normal functions of this organelle such as protein folding, protein quality control, calcium homeostasis and redox balance, promote accumulation of unfolded or misfolded proteins, a condition known as ER stress. Autoimmune diseases are characterized by inflammation, which has been associated with an ER stress condition. Interestingly, patients with these diseases contain circulating auto-antibodies against chaperone proteins (such as Calnexin and GRP94), thus affecting the folding and assembly of MHC class I and II glycoproteins and their loading with peptide. The main purpose of this article is to review the involvement of the protein quality control and unfolded protein response (UPR) in the ER protein homeostasis (proteostasis) and their alterations in autoimmune diseases. In addition, we describe the interaction between ER stress and inflammation and evidences are shown of how autoimmune diseases are associated with an ER stress condition, with a special emphasis on the second most prevalent autoimmune rheumatic disease, Sjögren's syndrome., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Parkinson's disease (PD) is a degenerative disorder characterized by several motor symptoms including shaking, rigidity, slow movement and difficult walking, which has been associated to the death of nigro-striatal dopaminergic neurons. >90% of PD patients also present olfactory dysfunction. Although the molecular mechanisms responsible for this disease are not clear, hereditary PD is linked to mutations in specific genes, including the PTEN-induced putative kinase 1 (PINK1). In this work we provide for the first time a thorough temporal description of the behavioral effects induced by a mutation in the PINK1 gene in adult Drosophila, a previously described animal model for PD. Our data suggests that the motor deficits associated to PD are fully revealed only by the third week of age. However, olfactory dysfunction is detected as early as the first week of age. We also provide immunofluorescence and neurochemical data that let us propose for the first time the idea that compensatory changes occur in this Drosophila model for PD. These compensatory changes are associated to specific components of the dopaminergic system: the biosynthetic enzymes, Tyrosine hydroxylase and Dopa decarboxylase, and the Dopamine transporter, a plasma membrane protein involved in maintaining dopamine extracellular levels at physiologically relevant levels. Thus, our behavioral, immunofluorescence and neurochemical data help define for the first time presymptomatic and symptomatic phases in this PD animal model, and that compensatory changes occur in the dopaminergic neurons in the presymptomatic stage., (Copyright © 2017 Elsevier B.V. All rights reserved.)

We consider the lifetime of a T cell clonotype, the set of T cells with the same T cell receptor, from its thymic origin to its extinction in a multiclonal repertoire. Using published estimates of total cell numbers and thymic production rates, we calculate the mean number of cells per TCR clonotype, and the total number of clonotypes, in mice and humans. When there is little peripheral division, as in a mouse, the number of cells per clonotype is small and governed by the number of cells with identical TCR that exit the thymus. In humans, peripheral division is important and a clonotype may survive for decades, during which it expands to comprise many cells. We therefore devise and analyse a computational model of homeostasis of a multiclonal population. Each T cell in the model competes for self pMHC stimuli, cells of any one clonotype only recognising a small fraction of the many subsets of stimuli. A constant mean total number of cells is maintained by a balance between cell division and death, and a stable number of clonotypes by a balance between thymic production of new clonotypes and extinction of existing ones. The number of distinct clonotypes in a human body may be smaller than the total number of naive T cells by only one order of magnitude., (Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The southern tip of South America and Antarctica are particularly interesting due to many genera and also species currently sharing between both areas. The genus Nacella (Patellogastropoda: Nacellidae) is distributed in different regions of South America and Antarctica living preferentially on rocks and boulders and grazing on algae, diatoms and bacterial films. We described the transcriptomes of three Nacella species, Nacella concinna (Strebel, 1908), inhabiting the Antarctic Peninsula; Nacella magallanica (Gmelin, 1791), from Patagonia and Nacella clypeater (Lesson, 1831), from central Chile. In total, we obtained over 20,000 contigs with an average length of 583bp. Homologous protein coding genes (PCGs) for mitochondrial genome of the three species were characterized and a database of molecular markers was also generated. This study represents the first publicly available report on pyrosequencing data for patellogastropod species, and provides an important comparative resource for studies in ecophysiology and evolutionary adaptation in marine invertebrate species., (Copyright © 2014 Elsevier B.V. All rights reserved.)

We analyse a mathematical model of the peripheral CD4(+) T cell population, based on a quorum-sensing mechanism, by which an optimum number of regulatory T cells can be established and maintained. We divide the population of a single T cell receptor specificity into four pools: naive, IL-2 producing, IL-2 non-producing, and regulatory CD4(+) T cells. Proliferation, death and differentiation of cells are introduced as transition probabilities of a stochastic Markov model, with the assumption that the amount of IL-2 available to CD4(+) T cells is proportional to the size of the population of IL-2 producing CD4(+) T cells. We explore the population dynamics both in the absence and in the presence of specific antigen. We study the establishment of the peripheral CD4(+) T cell pool from thymic output in the absence of antigen, and its return to homeostasis after an immune challenge, by steady state analysis of the deterministic approximation. The number of regulatory T cells at steady state is greater in the presence of antigen than in its absence. We also consider the stochastic dynamics of the model after an immune challenge, in particular the behaviour leading to ultimate extinction of the IL-2 producing and regulatory T cell populations., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

The purpose of this study was to investigate the influence of dietary potassium on the sodium effect on blood pressure (BP) in the general population and the adherence of current recommendations for sodium and potassium intake. An overnight (12-hour) urine sample was collected in a population-based study to investigate cardiovascular risk. A sub-sample of 1285 subjects (age range, 25-64 years) free from any medication interfering with BP or potassium excretion was studied. Of the participants, 86.0% consumed over 6 g of salt/day and 87.7% less than the recommended intake of potassium (4.7 g). Potassium excretion and the sodium to potassium ratio were significantly related to systolic and diastolic BP only in subjects consuming more than 6 g/day of salt. Subjects in the highest sodium to potassium ratio quartile (surrogate of unhealthy diet) presented 8 mm Hg and 7 mm Hg higher values of systolic and diastolic BP, respectively, when compared with the first quartile, while individuals in the fourth quartile of urinary potassium excretion (healthier diet) showed 6 mm Hg and 4 mm Hg lower systolic and diastolic BP, respectively, compared with the first quartile. Our data indicate that when people have an increased intake of potassium, high intake of sodium is not associated with higher BP., (Copyright © 2014 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.)

Sjögren's syndrome (SS) is a chronic autoimmune disease of undefined etiology. Patients with this syndrome suffer from severe alterations in both the quality and quantity of saliva and tears, due to impaired function of the relevant exocrine glands. Prevalent symptoms experienced by SS-patients include a persistent dry mouth sensation (xerostomia) and dry eyes (keratoconjunctivitis sicca). Water content of saliva depends of acetylcholine levels, glandular innervation, M3R signaling, calcium tunneling and water release, among other factors. However, unstimulated salivary flow correlates only poorly with symptoms of mouth dryness, raising the question as to which other components of saliva may be involved in mouth dryness experienced by SS-patients? Salivary mucins are glycoproteins characterized by the presence of large oligosaccharide side chains attached to the protein backbone. These molecules are key saliva components that are required to sequester water and thereby moisturize, as well as lubricate the oral mucosa. In the labial salivary glands of SS patients, morphological and functional alterations are detectable that affect the maturation and trafficking of salivary mucins. In this review, we will focus the discussion on these aspects of reduced salivary flow and decreased quality of salivary mucins, since they are likely to be responsible for xerostomia in SS-patients., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Objective: To determine the prevalence of metabolic syndrome and related factors in bank employees in the city of Vitória/ES, Brazil., Methods: This was a cross-sectional study that included 521 working men and women >20 years of age. Sociodemographic, lifestyle, anthropometric, biochemical, and hemodynamic characteristics were collected. Metabolic syndrome was diagnosed using the criteria of the National Cholesterol Education Program-ATPIII and the International Diabetes Federation. A logistic regression model was used to calculate the crude and adjusted OR of the variables, and the statistical level of significance was set at 5.0%., Results: We identified 86 (17.2%) and 113 (22.6%) subjects with metabolic syndrome according to the criteria of the National Cholesterol Education Program-ATPIII and the International Diabetes Federation, respectively. The risk of developing metabolic syndrome was higher in individuals with a high school education (OR 2.6 [CI(95%), 1.1-6.1]). In overweight and obese subjects, the risks were also higher (OR 12.6 [CI(95%), 4.8-33.2, p = 0.000] and OR 43.7% [CI(95%), 16.1-118.9, p = 0.000], respectively)., Conclusion: A large number of bank employees have metabolic syndrome, which can be associated with an increased risk of developing cardiovascular disease. Individuals who had college degrees had a higher prevalence of metabolic syndrome; this finding can be explained by the high rates of overweight and obesity found in subjects with college and graduate school educations.

It is now well appreciated that population structure can have a major impact on disease dynamics, outbreak sizes and epidemic thresholds. Indeed, on some networks, epidemics occur only for sufficiently high transmissibility, whereas in others (e.g. scale-free networks), no such threshold effect exists. While the effects of variability in connectivity are relatively well known, the effects of clustering in the population on disease dynamics are still debated. We develop a simple and intuitive model for calculating the reproductive number R(0) on clustered networks with arbitrary degree distribution. The model clearly shows that in general, clustering impedes epidemic spread; however, its effects are usually small and/or coupled with other topological properties of the network. The model is generalized to take into account degree-dependent transmissibility (e.g., relevant for disease vectors). The model is also used to easily rederive a known result concerning the formation of the giant component., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

T-cell activation in lymph nodes relies on encounters with antigen (Ag)-bearing dendritic cells (DCs) but the number of DCs required to initiate an immune response is unknown. Here we have used a combination of flow cytometry, 2-photon imaging, and computational modeling to quantify the probability of T cell-DC encounters. We calculated that the chance for a T cell residing 24 hours in a murine popliteal lymph nodes to interact with a DC was 8%, 58%, and 99% in the presence of 10, 100, and 1000 Ag-bearing DCs, respectively. Our results reveal the existence of a threshold in DC numbers below which T-cell responses fail to be elicited for probabilistic reasons. In mice and probably humans, we estimate that a minimum of 85 DCs are required to initiate a T-cell response when starting from precursor frequency of 10(-6). Our results have implications for the rational design of DC-based vaccines.

The antimicrobial property of chlorhexidine is believed to be associated with its interaction of bacterium membrane, which calls for research on the identification of membranes sites capable of drug binding. In this study, we investigated the interaction of chlorhexidine digluconate, a known agent with bactericidal and bacteriostatic activities employed in the treatment of periodontal diseases, with bacteria cell model systems by using Langmuir monolayers. The insertion of the drug caused the surface pressure-area isotherms for a mixed protein-lipid monolayer to be shifted to higher lipid molecular areas, which was the first indication of the action of chlorhexidine in the membrane model. Surface infrared spectroscopy pointed to intrinsic interactions of the drug with the hydrophobic part of the lipid, leading to a disruption of the lipid organization at the interface. Also, the secondary structure of the polypeptide model employed in this work has been changed, as a consequence of the drug interactions. Such change in the lipid-protein models could be confirmed when the membrane was transferred to glass ionomer cement as a solid support, which can be considered a model for dental surfaces. Therefore, chlorhexidine interacts with lipid and protein moieties supposed to be present in lipid membranes. This may have important implication in understanding how the drug acts on specific sites of the bacteria membrane., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Although neuroimaging is useful in differentiating ischemic (IS) from hemorrhagic (ICH) stroke in the Emergency Department, a wide-available rapid biochemical test would add advantages in the pre-hospital triage and management of stroke patients. Our aim was to examine the predictive value of a panel of blood-borne biomarkers to differentiate IS from ICH. Admission blood samples obtained within 24h from stroke symptoms onset were tested by ELISA for CRP, D-dimer, sRAGE, MMP9, S100B, BNP, NT-3, caspase-3, chimerin-II, secretagogin, cerebellin and NPY. The complete protocol was achieved in 915 patients (776 IS, 139 ICH). Among blood samples obtained <6 h from symptoms onset (n=337), S100B levels were increased in ICH (107.58 vs 58.70 pg/mL; p<0.001) whereas sRAGE levels were decreased (0.77 vs 1.02 ng/mL; p=0.009) as compared to IS. In this subset of patients S100B (OR 3.97 95% CI 1.82-8.68; p=0.001) and sRAGE (OR 0.22 95% CI 0.10-0.52; p<0.001) were independently associated with ICH. A regression tree was created by CART method showing good classification ability (AUC=0.762). Similar results were found for samples obtained within 3 h. In conclusion, a combination of biomarkers including those of the S100B/RAGE pathway seems promising to achieve a rapid biochemical diagnosis of IS versus ICH in the first hours from symptoms onset. This article is part of a Special Issue entitled: Translational Proteomics., (Copyright © 2012. Published by Elsevier B.V.)

The α₂-adrenergic system is involved in pain processing and inflammation-induced sensitization. α₂-adrenoceptor agonists induce analgesia, and this effect is greater when administered in combination with other analgesics. In the present study, we assessed a possible enhancement of antinociception combining the α₂-adrenoceptor agonist medetomidine with subeffective doses of NCX701 (nitroparacetamol). The effects of the drugs were studied in spinal cord neuronal responses from adult male Wistar rats with carrageenan-induced inflammation, using the recording of single motor unit technique. The experiments showed that the i.v. administration of medetomidine and NCX701 induced a more potent and effective antinociceptive effect than medetomidine when given alone (ID₅₀: 0.47±0.1 vs. 1.1±0.1 μg/kg) or in the presence of paracetamol, in naturally-evoked nociceptive responses. In addition, the duration of antinociception was significantly longer (P<0.001, 100 min after administration). The use of low doses of NCX701 and α₂-adrenoceptor agonists might open new perspectives in the treatment of inflammatory pain., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Response surface methodology (RSM) was used for the determination of optimum extraction parameters to reach maximum lipid extraction yield with yeast. Total lipids were extracted from oleaginous yeast (Rhodotorula glutinis) using pressurized liquid extraction (PLE). The effects of extraction parameters on lipid extraction yield were studied by employing a second-order central composite design. The optimal condition was obtained as three cycles of 15 min at 100°C with a ratio of 144 g of hydromatrix per 100 g of dry cell weight. Different analysis methods were used to compare the optimized PLE method with two conventional methods (Soxhlet and modification of Bligh and Dyer methods) under efficiency, selectivity and reproducibility criteria thanks to gravimetric analysis, GC with flame ionization detector, High Performance Liquid Chromatography linked to Evaporative Light Scattering Detector (HPLC-ELSD) and thin-layer chromatographic analysis. For each sample, the lipid extraction yield with optimized PLE was higher than those obtained with referenced methods (Soxhlet and Bligh and Dyer methods with, respectively, a recovery of 78% and 85% compared to PLE method). Moreover, the use of PLE led to major advantages such as an analysis time reduction by a factor of 10 and solvent quantity reduction by 70%, compared with traditional extraction methods., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Differentiation of epithelial cells is required to define tissue architecture and appropriate function of these cells is associated with a specific pattern of gene expression. DNA methylation, post-translational modification of histones and chromatin remodeling are nuclear mechanisms implicated in epigenetic control of gene expression. All factors relevant to tissue differentiation, including cell adhesion and shape, extracellular stimuli and transcriptional control, modulate gene expression and, thus, some of them are likely to impact on nuclear mechanisms of epigenetic control. The epithelial cells of salivary glands from Sjögren's syndrome patients display alterations in cell adhesion and shape. In this review, we summarize how these alterations are thought to lead to chromatin remodeling and, in doing so, bring about changes in transcriptional patterns. Additionally, we discuss how mechanotransduction in cells with impaired structural organization is implicated in modifying gene expression in these patients., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Recognition of antigens by the adaptive immune system relies on a highly diverse T cell receptor repertoire. The mechanism that maintains this diversity is based on competition for survival stimuli; these stimuli depend upon weak recognition of self-antigens by the T cell antigen receptor. We study the dynamics of diversity maintenance as a stochastic competition process between a pair of T cell clonotypes that are similar in terms of the self-antigens they recognise. We formulate a bivariate continuous-time Markov process for the numbers of T cells belonging to the two clonotypes. We prove that the ultimate fate of both clonotypes is extinction and provide a bound on mean extinction times. We focus on the case where the two clonotypes exhibit negligible competition with other T cell clonotypes in the repertoire, since this case provides an upper bound on the mean extinction times. As the two clonotypes become more similar in terms of the self-antigens they recognise, one clonotype quickly becomes extinct in a process resembling classical competitive exclusion. We study the limiting probability distribution for the bivariate process, conditioned on non-extinction of both clonotypes. Finally, we derive deterministic equations for the number of cells belonging to each clonotype as well as a linear Fokker-Planck equation for the fluctuations about the deterministic stable steady state., (Copyright 2010 Elsevier Ltd. All rights reserved.)

Background and Aims: The role of diet in the aetiology of metabolic syndrome (MetS) is not well understood. The aim of the present study was to evaluate the relationship between adherence to the Mediterranean diet (MedDiet) and MetS., Methods and Results: A cross-sectional study was conducted with 808 high cardiovascular risk participants of the Reus PREDIMED Centre. MetS was defined by the updated National Cholesterol and Education Program Adult Treatment Panel III criteria. An inverse association between quartiles of adherence to the MedDiet (14-point score) and the prevalence of MetS (P for trend<0.001) was observed. After adjusting for age, sex, total energy intake, smoking status and physical activity, participants with the highest score of adherence to the MedDiet (>/=9 points) had the lowest odds ratio of having MetS (OR [95% CI] of 0.44 [0.27-0.70]) compared to those in the lowest quartile. Participants with the highest MedDiet adherence had 47 and 54% lower odds of having low HDL-c and hypertriglyceridemia MetS criteria, respectively, than those in the lowest quartile. Some components of the MedDiet, such as olive oil, legumes and red wine were associated with lower prevalence of MetS., Conclusion: Higher adherence to a Mediterranean diet is associated with a significantly lower odds ratio of having MetS in a population with a high risk of cardiovascular disease.

The reliability of the immune response to pathogenic challenge depends critically on the size and diversity of the T cell repertoire. We study naïve T cell repertoire diversity maintenance by a stochastic model that incorporates the concept of competition between T cells for survival stimuli emanating from self-antigen presenting cells (APCs). In the mean field approximation we show that clonotype extinction is certain and compute mean extinction times. We introduce the concept of mean niche overlap and show that clones with a mean niche overlap greater than one have a short repertoire lifespan. This selection differential induces minimal recognition commonality between T cell receptors (TCRs) resulting in a diverse T cell repertoire.

Photopolymerized sol-gel monolithic columns for use in capillary electrochromatography were prepared in 125 microm i.d. polyacrylate-coated fused-silica capillaries. The polyacrylate-coating, unlike the polyimide one, is transparent to the radiation used (approximately 370 nm), and thus, no coating removal is necessary. This is a very important particularity since intrinsic capillary column characteristics, such as flexibility and mechanical resistance, are unchanged. A mixture containing metacryloxypropyltrimethoxysilane (MPTMS) as the polymeric precursor, hydrochloric acid as the catalyst, toluene as the porogen and bis(2,4,6-trimethylbenzoyl)-phenylphosphine oxide (Irgacure 819) as the photoinitiator was irradiated at 370 nm for 20 min inside the capillaries to prepare the columns through sol-gel approach. The versatility and viability of the use of polyacrilate as a new capillary external coating were shown through preparation of two columns under different conditions, which were tested in electrochromatography for separation of standard mixture containing thiourea (marker compound), propylbenzene, phenanthrene and pyrene.

We propose a new mathematical model of erythropoiesis that takes a positive feedback of erythrocytes on progenitor apoptosis into account, and incorporates a negative feedback of erythrocytes on progenitor self-renewal. The resulting model is a system of age-structured equations that reduces to a system of delay differential equations where the delays account for progenitor compartment duration and cell cycle length. We compare this model with experimental data on an induced-anemia in mice that exhibit damped oscillations of the hematocrit before it returns to equilibrium. When we assume no self-renewal of progenitors, we obtain an inaccurate fitting of the model with experimental data. Adding self-renewal in the progenitor compartment gives better approximations, with the main features of experimental data correctly fitted. Our results indicate the importance of progenitor self-renewal in the modelling of erythropoiesis. Moreover, the model makes testable predictions on the lifespan of erythrocytes confronted to a severe anemia, and on the progenitors behavior.

Background: Carotid angioplasty and stenting (CAS) with cerebral embolic protection is a safe alternative to carotid endarterectomy in high-risk patients. Among the various systems proposed for cerebral protection, transcervical CAS avoids crossing the lesion without protection and eliminates the complications associated with transfemoral access. This study analyzes our experience and the results obtained with a transcervical stenting technique for carotid revascularization., Methods: From January 2005 to June 2006, 62 CAS were performed in our center in high-risk patients with >70% stenosis (38.7% had a previous neurologic event and 61.3% were asymptomatic). The indications for CAS were severe heart disease (45.1%), severe pulmonary disease (6.4%), paralysis of the contralateral laryngeal nerve (6.4%), recurrent stenosis (3.2%), and high carotid lesion (1.6%). Twenty-one patients were >80 years old. A complete neurologic examination was performed by a stroke neurologist in all patients before and after stenting. The protection system used was carotid flow reversal by transcervical access. Transcranial Doppler monitoring was done during the procedure in 35 patients. We analyzed technical success, the presence of high-intensity transient signals during the procedure, neurologic morbidity and mortality at 30 days and 6 months, and stent patency at 6 months (range, 1 to 18 months). Technical success was 96.8%. Perioperative high-intensity transient signals were observed in two patients (5.7%). In the immediate postoperative period, one patient had a transient ischemic attack of the anterior cerebral artery and another had a stroke, with contralateral hemiplegia. At 48 hours after discharge, a third patient returned to the hospital with a severe cerebral hemorrhage that required surgical drainage; hence, neurologic morbidity was 4.9%. There were no deaths at 6 months. Among the total, 98.4% of the stents remained patent, two showed restenosis of 50% to 70%, and one restenosis of >70%. No patients presented a neurologic event during the follow-up., Conclusions: Transcervical carotid artery stenting with flow reversal cerebral protection is a relatively simple, safe technique that avoids instrumentation of the aortic arch and crossing the target lesion without protection. It is less expensive than techniques requiring a filter device and provides excellent outcome with an acceptable incidence of complications.

In this work, the analysis of a group of four fungicides (pyrimethanil, nuarimol, procymidone and cyprodinil) and one insecticide (pirimicarb) by micellar electrokinetic chromatography (MEKC) with UV detection using the on-line preconcentration strategy called reversed electrode polarity stacking mode (REPSM) is proposed. After optimisation, an adequate separation electrolyte for the separation and stacking of these pesticides was obtained which consisted of 100 mM borate, 60 mM sodium dodecyl sulphate (SDS), at pH 9.0 and 2% 2-propanol. The use of this running buffer together with the REPSM preconcentration method provided limits of detection (LODs) between 38.3 and 241 microg/L. In order to apply the developed methodology for the analysis of these pesticides in wine samples, several off-line preconcentration strategies (mainly, solid-phase extraction, SPE, and solid-phase microextraction, SPME) were tested. Although the use of a SPE procedure, optimized in this work for water samples, using Oasis HLB cartridges, provided mean recovery values between 79 and 100% for spiked water samples, it could not be applied to the extraction of these pesticides from wine samples due to high interference from the sample matrix. However, the use of a SPME procedure using polydimethylsiloxane/divynilbenzene (PDMS/DVB) fibers allowed the selective extraction of four of the five pesticides which could be perfectly determined. The final combination of the off-line SPME and on-line REPSM preconcentration strategies allowed obtaining LODs between 17.6 and 32.3 microg/L.

Viral quasispecies may possess a molecular memory of their past evolutionary history, imprinted on minority components of the mutant spectrum. Here we report experimental evidence and a theoretical model for memory in retroviral quasispecies in vivo. Apart from replicative memory associated with quasispecies dynamics, retroviruses may harbour a "cellular" or "anatomical" memory derived from their integrative cycle and the presence of viral reservoirs in body compartments. Three independent sets of data exemplify the two kinds of memory in human immunodeficiency virus type 1 (HIV-1). The data provide evidence of re-emergence of sequences that were hidden in cellular or anatomical compartments for extended periods of infection, and recovery of a quasispecies from pre-existing genomes. We develop a three-component model that incorporates the essential features of the quasispecies dynamics of retroviruses exposed to selective pressures. Significantly, a numerical study based on this model is in agreement with the experimental data, further supporting the existence of both replicative and reservoir memory in retroviral quasispecies.

The duration and fitness dependence of memory in viral quasispecies evolving in cell culture have been investigated using two genetic markers of foot-and-mouth disease virus (FMDV). In lineages of antigenic variant FMDV RED, which reverted to FMDV RGD, memory FMDV RED genomes were detected after 50 infectious cycles, and memory level was fitness dependent. In growth-competition experiments between a reference FMDV RGD and two different FMDV RED populations, a 7.6-fold higher fitness of the initial FMDV RED population resulted in 30 to 100-fold higher memory level. In lineages of low-fitness clones containing an elongated internal polyadenylate tract, revertants lacking excess adenylate residues became dominant by passage 20. However, genomes including a larger number of adenylate residues were detected as memory genomes after at least 150 infectious cycles. Thus, quasispecies memory can be durable and is fitness dependent, as predicted from the growth competition of two mutant forms of a genome. An understanding of factors influencing quasispecies memory levels and duration may have implications for the extended diagnosis of viruses based on the quantification of minority genomes., (Copyright 2002 Academic Press.)

Gastroaortic fistula following esophagogastrectomy is an uncommon and invariably fatal complication without urgent surgical intervention. We report 1 such case and review the world literature identifying 22 previous cases. It characteristically presents 2 to 3 weeks after esophagogastrectomy with an initial herald bleed, followed by a latent period with a mean duration of 10 hours (range: 30 minutes to 3 days) and final exsanguination. Only 1 patient in this series survived. Awareness is necessary to allow prompt diagnosis and treatment of this almost invariably lethal but curable condition.

High-flow pneumatically assisted electrospray (ESP) was applied to the characterization of triazine (atrazine, simazine, ametryne, cyanazine, deethylatrazine and deisopropylatrazine), phenylurea (chlortoluron++, isoproturon, diuron, linuron and diflubenzuron) and other priority herbicides (alachlor, metolachlor). In LC-ESP-MS the [M+Na]+ ion was used as the base peak in most cases, with the exception of chlorotriazines, which showed [M+H]+ as the base peak. When LC-TSP-MS was used, [M+H]+ was the base peak for many of the pesticides, with the exception of linuron and diflubenzuron, which showed [M+NH4]+ as the base peak. The ESP results were compared with those obtained with thermospray (TSP). LC-TSP-MS offered greater sensitivity for triazines than phenylurea herbicides, whereas the use of LC-ESP-MS offered an enhancement in sensitivity for phenylurea herbicides. As regards the fragmentation obtained using both techniques, ESP offered a considerable amount of structural information for the different chlorotriazines studied when the extraction voltage was increased from 20 to 40 V. Liquid-liquid extraction with dichloromethane was used for the trace enrichment of the different herbicides in estaurine water samples from the Elorn river (France). The presence of the different triazine metabolites, atrazine, simazine, metolachlor, isoproturon and diuron was confirmed by both LC-MS techniques.