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Summary: Background: Low rates of postnatal retention in HIV care and viral suppression have been reported in women living with HIV (WLWH) despite viral suppression at delivery. At the same time, postpartum follow-up is of crucial importance in light of the increasing support offered in many resource-rich countries including Switzerland to WLWH choosing to breastfeed their infant, if optimal scenario criteria are met. Methods: We longitudinally investigated retention in HIV care, viral suppression, and infant follow-up in a prospective multicentre HIV cohort study of WLWH in the optimal scenario who had a live birth between January 2000 and December 2018. Risk factors for adverse outcomes in the first year postpartum were assessed using logistic and proportional hazard models. Findings: Overall, WLWH were retained in HIV care for at least six months after 94.2% of the deliveries (694/737). Late start of combination antiretroviral therapy (cART) during the third trimester was found to be the main risk factor for failure of retention in HIV care (crude odds ratio [OR] 3.91; 95% confidence interval [CI], 1.50–10.22; p = 0.005). Among mothers on cART until at least one year after delivery, 4.4% (26/591) experienced viral failure, with illicit drugs use being the most important risk factor (hazard ratio [HR], 13.2; 95% CI, 2.35–73.6; p = 0.003). The main risk factors for not following the recommendations regarding infant follow-up was maternal depression (OR, 3.52; 95% CI, 1.18–10.52; p = 0.024). Interpretation: Although the results are reassuring, several modifiable risk factors for adverse postpartum outcome, such as late treatment initiation and depression, were identified. These factors should be addressed in HIV care of all WLWH, especially those opting to breastfeed in resource-rich countries. Funding: This study has been financed within the framework of the Swiss HIV Cohort Study, supported by the Swiss National Science Foundation (grant #201369), by SHCS project 850 and by the SHCS research foundation.

MitoNEET is a mitochondrial [2Fe-2S]-containing protein known for its involvement in cellular metabolism, iron regulation, and oxidative stress. The protein has been associated with diseases ranging from diabetes to Parkinson's disease, prompting the development of compounds designed to target mitoNEET selectively. Unfortunately, drug development is limited due to a lack of mechanistic understanding of how mitoNEET integrates into pathophysiological processes, and biological compounds that govern mitoNEET function are still ill-defined. We demonstrate an oxygen-dependent reaction with biological thiols catalyzed by mitoNEET. Specifically, we observed that mitoNEET converts L-cysteine to cystine. Finally, we showed that reduced glutathione (L-GSH) regulates the reactivity of two lipid-derived biomarkers of oxidative stress, 4-HNE and 4-ONE, towards mitoNEET. We found that exposure to L-GSH before treatment with either of the electrophilic aldehydes prevents the formation of a covalently linked mitoNEET dimer. Meanwhile, adding L-GSH after electrophile treatment recovers mitoNEET from the 4-HNE induced modification but not from the modification induced by 4-ONE. These results indicate a possible role for mitoNEET in thiol-mediated oxidative stress and may facilitate the development of drugs designed to modulate mitoNEET activity to improve pathophysiological states.

One of the world's crucial areas for crude oil exploration and extraction is the southern Gulf of Mexico, where Terminos Lagoon (TL) is located. Sediments from the TL region were used to assess the spatial patterns, origins, and ecotoxicological risks associated with 16 priority polycyclic aromatic hydrocarbons (PAHs; 3.1-248.9 ng⸳g -1 dry weight basis, dw) and trace metals (Ni = 11.0-104.0 mg⸳kg -1 ; V = 2.0-35.0 mg⸳kg -1 dw) linked to anthropogenic activities. Although origin indices based on PAHs and metals concentrations indicate no crude oil pollution in the region, sources of pyrogenic PAHs were identified. A chemometric approach demonstrated associations between organic matter and PAHs, and that metal accumulation depends mostly by the input of lithogenic materials. Ecotoxicological risk estimations showed a higher risk of possible adverse effects in sites near swamps and mangrove zones, highlighting the need of future monitoring. This study provides a reference for policymakers to conserve Mexico's largest coastal lagoon and other oil-impacted coastal areas worldwide., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Leishmaniasis and Chagas disease are parasitic infections that affect millions of people worldwide, producing thousands of deaths per year. The current treatments against these pathologies are not totally effective and produce some side effects in the patients. Acrylonitrile derivatives are a group of compounds that have shown activity against these two diseases. In this work, four novels synthetic acrylonitriles were evaluated against the intracellular form and extracellular forms of L. amazonensis and T. cruzi. The compounds 2 and 3 demonstrate to have good selectivity indexes against both parasites, specifically the compound 3 against the amastigote form (SI = 6 against L. amazonensis and SI = 7.4 against T. cruzi). In addition, the parasites treated with these two compounds demonstrate to produce a programmed cell death, since they were positive for the events studied related to this type of death, including chromatin condensation, accumulation of reactive oxygen species and alteration of the mitochondrial membrane potential. In conclusion, this work confirms that acrylonitriles is a source of possible new compounds against kinetoplastids, however, more studies are needed to corroborate this activity., Competing Interests: Conflict of interest The authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: To compare the ophthalmic artery Doppler peak systolic velocity ratio (OA PSV-ratio) and soluble fms-like tyrosine kinase-1/placental growth factor ratio (sFlt-1/PlGF ratio) in predicting adverse maternal and perinatal outcomes in women presenting with new onset hypertension., Study Design: Prospective cohort study in a specialist hypertension clinic, within a tertiary referral centre., Main Outcome Measures: Comparison between the OA PSV-ratio and sFlt-1/PlGF ratio in predicting delivery within one week from presentation and adverse maternal and perinatal outcomes e.g. severe hypertension, neonatal unit admission, small for gestational age., Results: Women who delivered within one week, compared to those who did not, had a higher OA PSV-ratio (0.82 vs 0.71, p < 0.01) and sFlt-1/PlGF ratio (93.3 vs 40.5, p = 0.08). Independent predictors of the OA PSV-ratio included mean arterial pressure and maternal weight and predictors of the sFlt-1/PlGF ratio included diastolic blood pressure and use of antihypertensive medications. Prediction of adverse outcomes with both ratios were similar and only modest e.g. AUROC for predicting delivery within one week for OA PSV-ratio was 0.57 (95% CI 0.47-0.67) and for sFlt-1/PlGF ratio was 0.61 (95% CI 0.52-0.70) (p = 0.53)., Conclusions: In women presenting with new onset hypertension, the OA PSV-ratio and sFlt-1/PlGF ratio have similar and modest performance in predicting adverse outcomes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Postcardiotomy venoarterial extracorporeal membrane oxygenation (VA ECMO) is characterized by discrepancies between weaning and survival-to-discharge rates. This study analyzes the differences between postcardiotomy VA ECMO patients who survived, died on ECMO, or died after ECMO weaning. Causes of death and variables associated with mortality at different time points are investigated., Methods: The retrospective, multicenter, observational Postcardiotomy Extracorporeal Life Support Study (PELS) includes adults requiring postcardiotomy VA ECMO between 2000 and 2020. Variables associated with on-ECMO mortality and postweaning mortality were modeled using mixed Cox proportional hazards, including random effects for center and year., Results: In 2058 patients (men, 59%; median age, 65 years; interquartile range [IQR], 55-72 years), weaning rate was 62.7%, and survival to discharge was 39.6%. Patients who died (n = 1244) included 754 on-ECMO deaths (36.6%; median support time, 79 hours; IQR, 24-192 hours), and 476 postweaning deaths (23.1%; median support time, 146 hours; IQR, 96-235.5 hours). Multiorgan (n = 431 of 1158 [37.2%]) and persistent heart failure (n = 423 of 1158 [36.5%]) were the main causes of death, followed by bleeding (n = 56 of 754 [7.4%]) for on-ECMO mortality and sepsis (n = 61 of 401 [15.4%]) for postweaning mortality. On-ECMO death was associated with emergency surgery, preoperative cardiac arrest, cardiogenic shock, right ventricular failure, cardiopulmonary bypass time, and ECMO implantation timing. Diabetes, postoperative bleeding, cardiac arrest, bowel ischemia, acute kidney injury, and septic shock were associated with postweaning mortality., Conclusions: A discrepancy exists between weaning and discharge rate in postcardiotomy ECMO. Deaths occurred during ECMO support in 36.6% of patients, mostly associated with unstable preoperative hemodynamics. Another 23.1% of patients died after weaning in association with severe complications. This underscores the importance of postweaning care for postcardiotomy VA ECMO patients., (Copyright © 2023 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Obesity is an important health problem in cardiac surgery and among patients requiring postcardiotomy venoarterial extracorporeal membrane oxygenation (V-A ECMO). Still, whether these patients are at risk for unfavorable outcomes after postcardiotomy V-A ECMO remains unclear. The current study evaluated the association between body mass index (BMI) and in-hospital outcomes in this setting., Methods: The Post-cardiotomy Extracorporeal Life Support (PELS-1) study is an international, multicenter study. Patients requiring postcardiotomy V-A ECMO in 36 centers from 16 countries between 2000 and 2020 were included. Patients were divided in 6 BMI categories (underweight, normal weight, overweight, class I, class II, and class III obesity) according to international recommendations. Primary outcome was in-hospital mortality, and secondary outcomes included major adverse events. Mixed logistic regression models were applied to evaluate associations between BMI and mortality., Results: The study cohort included 2046 patients (median age, 65 years; 838 women [41.0%]). In-hospital mortality was 60.3%, without statistically significant differences among BMI classes for in-hospital mortality (P = .225) or major adverse events (P = .126). The crude association between BMI and in-hospital mortality was not statistically significant after adjustment for comorbidities and intraoperative variables (class I: odds ratio [OR], 1.21; 95% CI, 0.88-1.65; class II: OR, 1.45; 95% CI, 0.86-2.45; class III: OR, 1.43; 95% CI, 0.62-3.33), which was confirmed in multiple sensitivity analyses., Conclusions: BMI is not associated to in-hospital outcomes after adjustment for confounders in patients undergoing postcardiotomy V-A ECMO. Therefore, BMI itself should not be incorporated in the risk stratification for postcardiotomy V-A ECMO., (Copyright © 2023 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Atherosclerosis is an inflammatory disease that involves antibody immune responses. Progression of hyperlipidemia can lead to atherosclerosis and subsequently cardiovascular diseases with high mortality. Additional lipid-lowering therapies other than statins are currently being studied, such as monoclonal antibodies. In this contemporary review, we examine the various monoclonal antibody therapies targeted toward atherosclerotic disease., (Published by Elsevier Inc.)

Black Carbon (BC) is an important component of household air pollution (HAP) in low- and middle- income countries (LMICs), but levels and drivers of exposure are poorly understood. As part of the Prospective Urban and Rural Epidemiological (PURE) study, we analyzed 48-hour BC measurements for 1187 individual and 2242 household samples from 88 communities in 8 LMICs (Bangladesh, Chile, China, Colombia, India, Pakistan, Tanzania, and Zimbabwe). Light absorbance (10 -5  m -1 ) of collected PM 2.5 filters, a proxy for BC concentrations, was calculated via an image-based reflectance method. Surveys of household/personal characteristics and behaviors were collected after monitoring. The geometric mean (GM) of personal and household BC measures was 2.4 (3.3) and 3.5 (3.9)·10 -5  m -1 , respectively. The correlation between BC and PM 2.5 was r = 0.76 for personal and r = 0.82 for household measures. A gradient of increasing BC concentrations was observed for cooking fuels: BC increased 53% (95%CI: 30, 79) for coal, 142% (95%CI: 117, 169) for wood, and 190% (95%CI: 149, 238) for other biomass, compared to gas. Each hour of cooking was associated with an increase in household (5%, 95%CI: 3, 7) and personal (5%, 95%CI: 2, 8) BC; having a window in the kitchen was associated with a decrease in household (-38%, 95%CI: -45, -30) and personal (-31%, 95%CI: -44, -15) BC; and cooking on a mud stove, compared to a clean stove, was associated with an increase in household (125%, 95%CI: 96, 160) and personal (117%, 95%CI: 71, 117) BC. Male participants only had slightly lower personal BC (-0.6%, 95%CI: -1, 0.0) compared to females. In multivariate models, we were able to explain 46-60% of household BC variation and 33-54% of personal BC variation. These data and models provide new information on exposure to BC in LMICs, which can be incorporated into future exposure assessments, health research, and policy surrounding HAP and BC., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2021. Published by Elsevier B.V.)

Carbapenem-resistant Klebsiella pneumoniae is a critical priority pathogen according to the World Health Organization's classification. Effluents of municipal wastewater treatment plants (EWWTP) may be a route for K. pneumoniae dissemination. Herein, the inactivation of this microorganism in simulated EWWTP by the photo-electro-oxidation (PEO) and photo-electro-Fenton (PEF) processes was evaluated. Firstly, the disinfecting ability and action pathways of these processes were established. PEO achieved faster K. pneumoniae inactivation (6 log units in 75 min of treatment) than the PEF process (6 log units in 105 min of treatment). PEO completely inactivated K. pneumoniae due to the simultaneous action of UVA light, electrogenerated H 2 O 2, and anodic oxidation pathways. The slower inactivation of K. pneumoniae when using PEF was related to interfering screen effects of iron oxides on light penetration and the diffusion of the bacteria to the anode. However, both PEO and PEF avoided the recovery and regrowth of treated bacteria (with no detectable increase in the bacteria concentration after 24 h of incubation). In addition to the bacteria evolution, the effect of treatment processes on the resistance gene was examined. Despite inactivation of K. pneumoniae by PEF was slower than by PEO, the former process induced a stronger degrading action on the gene, conferring the resistance to carbapenems (PEF had a Ct value of 24.92 cycles after 105 min of treatment, while PEO presented a Ct of 19.97 cycles after 75 min). The results of this research indicate that electrochemical processes such as PEO and PEF are highly effective at dealing with resistant K. pneumoniae in the EWWTP matrix., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Spinal cord glioblastoma is a rare disease, with an aggressive course and a poor prognosis. We describe magnetic resonance imaging (MRI) findings, in 3 adult cases of biopsy-confirmed glioblastoma. Conventional MRI findings were unclear with regard to the differential diagnosis between this rare tumor and other more common spinal cord lesions, including less aggressive tumors such as ependymoma or pilocytic astrocytoma, abscesses or tumefactive demyelinating lesions. After reasonable exclusion of infectious/inflammatory conditions, a final diagnosis of glioblastoma was established based on histopathological analysis. The cases reported reflect the difficulty of early radiological diagnosis of spinal cord glioblastoma, and indicate the need to perform a biopsy once inflammatory-infectious conditions are excluded with appropriate laboratory tests., (© 2020 Published by Elsevier Inc. on behalf of University of Washington.)

Crude oil and its derivatives are still the primary source of energy for humankind. However, during its transportation and treatment, spills of this resource can occur in aquatic environments. Nile tilapia is one of the most globally widespread fish species. This species is even found in brackish water due to its tolerance to salinity and pollution. In this study, the performance of brain cells (mitochondrial membrane potential [ΔΨm], calcium [Ca 2+ ] and O 2 and H 2 O 2 levels) exposed to crude oil was assessed. In addition, fatty acid metabolism (cholesterol concentration and fatty acid synthase [FAS], acyl CoA-oxidase [AOX] and catalase [CAT] activities) in the brain, heart, liver and intestine of Nile tilapia exposed to the water-accommodated fraction (WAF) of 0.01, 0.1 or 1 g/L Maya crude oil (MCO) for 96 h were evaluated. After exposure, in brain cells, there were only increases in ROS and slight reductions in ΔΨm. Exposure to WAF of MCO induced and increased the levels of cholesterol and altered FAS and AOX activities in all examined tissues. The brain is the most susceptible organ to alterations in the activity of fatty acid metabolic enzymes and cholesterol levels relative to the heart, liver and intestine. The correlation between inhibition of the activity of CAT and AOX suggests a possible reduction in the proliferation and size of peroxisomes. Most biomarkers were significantly altered in the brains of Nile tilapia exposed to the WAF containing 1 g/L MCO in comparison to the control., Competing Interests: Declaration of competing interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Crude oil (CO) is a super mixture of chemical compounds whose toxic effects are reported in fish species according to international guidelines. In the current study a proteomic analysis of oxidized proteins (ox) was performed on the brain and liver of Nile tilapia exposed to WAF obtained from relevant environmental loads (0.01, 0.1 and 1.0 g/L) of Maya CO. Results have shown that oxidation of specific proteins was a newly discovered organ-dependent process able to disrupt key functions in Nile tilapia. In control fish, enzymes involved on aerobic metabolism (liver aldehyde dehydrogenase and brain dihydrofolate reductase) and liver tryptophan--tRNA ligase were oxidized. In WAF-treated liver specimens, fructose-bisphosphate aldolase (FBA), β-galactosidase (β-GAL) and dipeptidyl peptidase 9 (DPP-9) were detected in oxidized form. oxDPP-9 could be favorable by reducing the risk associated with altered glucose metabolism, the opposite effects elicited by oxFBA and oxβ-GAL. oxTrypsin showed a clear adverse effect by reducing probably the hepatocyte capacity to achieve proteolysis of oxidized proteins as well as for performing the proper digestive function. Additionally, enzyme implicated in purine metabolism adenosine (deaminase) was oxidized. Cerebral enzymes of mitochondrial respiratory chain complex (COX IV, COX5B), of glycosphingolipid biosynthesis (β-N-acetylhexosaminidase), involved in catecholamines degradation (catechol O-methyltransferase), and microtubule cytoskeleton (stathmin) were oxidized in WAF-treated specimens. This response suggests, in the brain, an adverse scenario for the mitochondrial respiration process and for ATP provision as for ischemia/reoxygenation challenges. Proteomic analysis of oxidized proteins is a promising tool for monitoring environmental quality influenced by hydrocarbons dissolved in water., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Diatoms play key roles in primary production and carbon fixation at a global scale and in some cases these species live on marine ecosystems impacted by crude oil (CO) spills. Halamphora oceanica, a new diatom species from the Southwest of the Gulf of Mexico was isolated and cultured in the laboratory and was exposed to water accommodated fraction (WAF) of different Maya CO loads at 0.01, 0.1, 1 and 10g/L by 96h. A battery of biomarkers involved in oxidative stress (O 2 •, H 2 O 2 , TBARS, ROOH, RC=O, SOD, CAT, GPx), biotransformation and conjugation (total CYP450 activity and GST) moreover fatty acid (FA) metabolism (FA levels, fatty-acid synthase and acyl-CoA oxidase) were measured. Obtained results suggest that increases of PAHs in the medium (below to EC 50 ) acts as external forces able to turn-on regulatory mechanisms on H. oceanica involved in both, on the PAHs uptake and changing its aerobic metabolism to anaerobic metabolism. However, the growth of this microalgae species evaluated as chlorophyll "a" and pheophytin levels increased as the WAF concentration indicating that PAHs and other hydrosoluble hydrocarbons were used as carbon and energy sources by unidentified enzymes not evaluated in the current study. Our hypothesis was also corroborated by IBRv2. In the current study, we suppose the change from aerobic to anaerobic metabolism as a strategy for Halamphora oceanica survival exposed to petroleum hydrocarbons., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Health care-associated meningitis and ventriculitis (HCAMV) occurs in adults with intracranial hemorrhage (ICH) and is associated with high rates of morbidity and mortality, but the prognostic impact of this infectious complication in a controlled matched study of ICH is unknown., Methods: We conducted a case-control study of adult patients with ICH and HCAMV at a large tertiary care hospital in Houston, Texas, from 2003 to 2016. Cases were defined as patients with ICH and HCAMV as documented by a positive cerebrospinal fluid culture. Controls were defined as patients with ICH without evidence of HCAMV. An adverse clinical outcome was defined as a Glasgow Outcome Scale score of ≤4., Results: This study included 120 patients with ICH; 40 patients also had HCAMV, whereas 80 patients had ICH with no evidence of HCAMV. Cases and controls were appropriately matched by age, Glasgow Coma Scale score, and Acute Physiology and Chronic Health Evaluation II score (P > 0.05). Patients with ICH and meningitis had more comorbidities, higher rates of abnormal neurologic examination, hypoglycorrhachia, and elevated cerebrospinal fluid lactate levels (P < 0.05). Adverse clinical outcomes were greater in patients with HCAMV and ICH than in patients with ICH alone (83% vs. 30%; P < 0.001). On logistic regression analysis, independent risk factors associated with an adverse outcome were HCAMV and mechanical ventilation (P < 0.05)., Conclusions: HCAMV has a significant prognostic impact in adults with ICH., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Vertical profiles of deep-water fluorescence determined by the chlorophyll sensor, polycyclic aromatic hydrocarbons, biomarkers, and other miscellaneous parameters measured in the southern Gulf of Mexico are reported. In the course of the survey, unexpected deep fluorescences were recorded (>1100m depth) in half of the 40 stations studied, a novel finding in this area of the Gulf. Currently, the deep-water fluorescence phenomenon is not completely understood, however we observe linear correlation between the fluorescence intensity and chlorophyll-α concentrations and coincidence of higher number of hydrocarbonoclastic bacteria in samples collected precisely in the deep-water fluorescence. This information is particularly interesting in relation to the Deepwater Horizon oil spill in 2010, in view that the aftermaths of the spill can be observed till today as oil plumes trapped in deep water layers that may disturb the natural water ecosystem., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Viral central nervous system (CNS) infections are typically characterized by a cerebrospinal fluid (CSF) lymphocytic pleocytosis. A CSF neutrophilic pleocytosis presentation has been described, but its prognostic and clinical significance is unknown. The objectives of this study were to (1) compare the clinical and laboratory characteristics of viral CNS infections with a CSF neutrophilic pleocytosis to those with a lymphocytic pleocytosis, and (2) evaluate factors associated with an adverse clinical outcome., Methods: A retrospective study of patients with confirmed viral CNS infections was conducted. The patients were divided into those with CSF neutrophilic pleocytosis and those with CSF lymphocytic pleocytosis. Clinical findings and outcomes were compared between the two groups., Results: Of the 182 patients included in the study, 45 (24.7%) had CSF neutrophilic pleocytosis. Enterovirus infections were the cause of 64% of neutrophil-predominant CSF and 33% of lymphocyte-predominant CSF (p<0.001), while herpes infections were the cause of 46% of lymphocytic pleocytosis and 20% of neutrophilic pleocytosis (p=0.003). Moreover, neutrophilic pleocytosis was seen more commonly in younger patients (p=0.001), patients with respiratory symptoms (p=0.04), and patients with higher CSF white cell counts (p=0.004). Twenty-nine patients had an adverse clinical outcome (15.9%); the only predictor independently associated with an adverse clinical outcome on multivariable logistic regression analysis was an encephalitis presentation (p=0.01)., Conclusions: The results of a study exploring the association between CSF neutrophilic pleocytosis and clinical and prognostic significance are presented here. This study suggests that CSF neutrophilic pleocytosis is not associated with higher adverse clinical outcomes., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)

This study focuses on the detection and identification of DNA and antibodies to Ehrlichia spp. in samples of blood bank donors in Costa Rica using molecular and serological techniques. Presence of Ehrlichia canis was determined in 10 (3.6%) out of 280 blood samples using polymerase chain reaction (PCR) targeting the ehrlichial dsb conserved gene. Analysis of the ehrlichial trp36 polymorphic gene in these 10 samples revealed substantial polymorphism among the E. canis genotypes, including divergent tandem repeat sequences. Nucleotide sequences of dsb and trp36 amplicons revealed a novel genotype of E. canis in blood bank donors from Costa Rica. Indirect immunofluorescence assay (IFA) detected antibodies in 35 (35%) of 100 serum samples evaluated. Thirty samples showed low endpoint titers (64-256) to E. canis, whereas five sera yielded high endpoint titers (1024-8192); these five samples were also E. canis-PCR positive. These findings represent the first report of the presence of E. canis in humans in Central America., (Copyright © 2016 Elsevier GmbH. All rights reserved.)

Background & Aims: Hepatitis C (HCV) is a leading cause of morbidity and mortality in people who live with HIV. In many countries, access to direct acting antiviral agents to treat HCV is restricted to individuals with advanced liver disease (METAVIR stage F3 or F4). Our goal was to estimate the long term impact of deferring HCV treatment for men who have sex with men (MSM) who are coinfected with HIV and often have multiple risk factors for liver disease progression., Methods: We developed an individual-based model of liver disease progression in HIV/HCV coinfected MSM. We estimated liver-related morbidity and mortality as well as the median time spent with replicating HCV infection when individuals were treated in liver fibrosis stages F0, F1, F2, F3 or F4 on the METAVIR scale., Results: The percentage of individuals who died of liver-related complications was 2% if treatment was initiated in F0 or F1. It increased to 3% if treatment was deferred until F2, 7% if it was deferred until F3 and 22% if deferred until F4. The median time individuals spent with replicating HCV increased from 5years if treatment was initiated in F2 to almost 15years if it was deferred until F4., Conclusions: Deferring HCV therapy until advanced liver fibrosis is established could increase liver-related morbidity and mortality in HIV/HCV coinfected individuals, and substantially prolong the time individuals spend with a replicating HCV infection., (Copyright © 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background: Tuberculosis (TB) is the leading cause of death in South Africa. The burden of disease varies by age, with peaks in TB notification rates in the HIV-negative population at ages 0-5, 20-24, and 45-49 years. There is little variation between age groups in the rates in the HIV-positive population. The drivers of this age pattern remain unknown., Methods: We developed an age-structured simulation model of Mycobacterium tuberculosis (Mtb) transmission in Cape Town, South Africa. We considered five states of TB progression: susceptible, infected (latent TB), active TB, treated TB, and treatment default. Latently infected individuals could be re-infected; a previous Mtb infection slowed progression to active disease. We further considered three states of HIV progression: HIV negative, HIV positive, on antiretroviral therapy. To parameterize the model, we analysed treatment outcomes from the Cape Town electronic TB register, social mixing patterns from a Cape Town community and used literature estimates for other parameters. To investigate the main drivers behind the age patterns, we conducted sensitivity analyses on all parameters related to the age structure., Results: The model replicated the age patterns in HIV-negative TB notification rates of Cape Town in 2009. Simulated TB notification rate in HIV-negative patients was 1000/100,000 person-years (pyrs) in children aged <5 years and decreased to 51/100,000 in children 5-15 years. The peak in early adulthood occurred at 25-29 years (463/100,000 pyrs). After a subsequent decline, simulated TB notification rates gradually increased from the age of 30 years. Sensitivity analyses showed that the dip after the early adult peak was due to the protective effect of latent TB and that retreatment TB was mainly responsible for the rise in TB notification rates from the age of 30 years., Conclusion: The protective effect of a first latent infection on subsequent infections and the faster progression in previously treated patients are the key determinants of the age-structure of TB notification rates in Cape Town., (Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.)

Objectives: Hypoglycorrhachia (cerebrospinal fluid (CSF) glucose <45 mg/dl) has been identified as a prognostic factor in patients with meningitis. The differential diagnosis of hypoglycorrhachia and its clinical significance was analyzed in the present study., Methods: This was a retrospective study of 620 adult patients with community-acquired meningitis (CSF white blood cell count >5 × 10(6) cells/l and absence of a CSF shunt or recent neurosurgical procedure (<1 month)) at eight Memorial Hermann hospitals in Houston, Texas, from January 2005 to December 2010. An adverse clinical outcome was defined as a Glasgow outcome scale score of ≤ 4., Results: Out of 620 patients with meningitis, 116 (19%) had hypoglycorrhachia. Etiologies of hypoglycorrhachia were idiopathic (n=40), bacterial (n=27), cryptococcal (n=26), viral (n=15), and tuberculous (n=4). Patients with hypoglycorrhachia were more likely to be immunosuppressed, have a history of intravenous drug use, and present with a vesicular or petechial rash, nausea or vomiting, nuchal rigidity, sinusitis/otitis, abnormal mental status, and focal neurological deficits compared to those patients without hypoglycorrhachia (p<0.05). Additionally, patients in the hypoglycorrhachia group had significantly higher rates of positive CSF and blood cultures, urgent treatable conditions, and abnormal cranial imaging (p<0.05). Furthermore, patients with hypoglycorrhachia had more adverse clinical outcomes (26/116 (22.4%) vs. 45/504 (8.9%); p<0.001)., Conclusion: Hypoglycorrhachia has significant clinical and prognostic value in the evaluation of adult patients with community-acquired meningitis., (Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Metabolomics research, like other disciplines utilizing high-throughput technologies, generates a large amount of data for every sample. Although handling this data is a challenge and one of the biggest bottlenecks of the metabolomics workflow, it is also the clue to accomplish valuable results. This work has been designed to supply methodological data mining guidelines, describing systematically the steps to be followed in metabolomics data exploration. Instrumental raw data refinement in the pre-processing step and assessment of the statistical assumptions in pre-treatment directly affect the results of subsequent univariate and multivariate analyses. A study of aging in a healthy population was selected to represent this data mining process. Multivariate analysis of variance and linear regression methods were used to analyze the metabolic changes underlying aging. Selection of both multivariate methods aims to illustrate the treatment of age from two rather different perspectives, as a categorical variable and a continuous variable., Biological Significance: Metabolomics is a discipline involving the analysis of a large amount of data to gather relevant information. Researchers in this field have to overcome the challenges of complex data processing and statistical analysis issues. A wide range of tasks has to be executed, from the minimization of batch-to-batch/systematic variations in pre-processing, to the application of common data analysis techniques relying on statistical assumptions. In this work, a real-data metabolic profiling research on aging was used to illustrate the proposed workflow and suggest a set of guidelines for analyzing metabolomics data. This article is part of a Special Issue entitled: HUPO 2014., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Aim: It is established that axillary dissection (AD) can be safely avoided in breast cancer patients with a negative sentinel node (SN). In the present study we assessed whether the rate of axillary disease was sufficiently low on long term follow-up to consolidate the policy of AD avoidance., Methods: We retrospectively analysed data on 5262 consecutive primary breast cancer patients with clinically negative axilla and negative SN, treated from 1996 to 2006, who did not receive AD. We used univariate and multivariate analyses to assess the influence of patient and tumour characteristics on first events and survival. The primary endpoint was the development of axillary disease as first event., Results: After a median follow-up of 7.0 years (interquartile range 5.4-8.9 years) survival for the series was high (91.3%; 95% CI 90.3-92.3 at 10 years) and only 91 (1.7%) patients developed axillary disease as first event. Axillary disease was significantly more frequent in patients with the following characteristics: <35 years at diagnosis, tumour >1 cm, multifocality/multicentricity, G3, ductal histotype, Ki67 ≥ 30%, peritumoral vascular invasion, luminal B-like subtype, HER2 positivity, mastectomy, and not receiving radiotherapy., Conclusion: Long-term follow-up of our large series confirms that axillary metastasis is infrequent when AD is omitted in SN-negative breast cancer patients, and has low impact on overall survival., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Mycobacterium tuberculosis isolates with identical IS6110 restriction fragment length polymorphism (RFLP) patterns are considered to be clonally related. The presence of IS6110 in the dnaA-dnaN intergenic region, one preferential locus for the integration of IS6110, was evaluated in 125 M. tuberculosis isolates. Five isolates had IS6110 inserted in this region, and two consisted of a mix of isogenic strains that putatively have evolved during a single infection. Strains from the same isolate had identical spoligo and mycobacterial interspersed repetitive unit-variable-number tandem repeat profiles, but had slight variations in IS6110 RFLP patterns, due to the presence of IS6110 in the dnaA-dnaN intergenic region. Duplication of the dnaA-dnaN intergenic region was found in one isogenic strain.

Muscle contraction involves the interaction of the myosin heads of the thick filaments with actin subunits of the thin filaments. Relaxation occurs when this interaction is blocked by molecular switches on these filaments. In many muscles, myosin-linked regulation involves phosphorylation of the myosin regulatory light chains (RLCs). Electron microscopy of vertebrate smooth muscle myosin molecules (regulated by phosphorylation) has provided insight into the relaxed structure, revealing that myosin is switched off by intramolecular interactions between its two heads, the free head and the blocked head. Three-dimensional reconstruction of frozen-hydrated specimens revealed that this asymmetric head interaction is also present in native thick filaments of tarantula striated muscle. Our goal in this study was to elucidate the structural features of the tarantula filament involved in phosphorylation-based regulation. A new reconstruction revealed intra- and intermolecular myosin interactions in addition to those seen previously. To help interpret the interactions, we sequenced the tarantula RLC and fitted an atomic model of the myosin head that included the predicted RLC atomic structure and an S2 (subfragment 2) crystal structure to the reconstruction. The fitting suggests one intramolecular interaction, between the cardiomyopathy loop of the free head and its own S2, and two intermolecular interactions, between the cardiac loop of the free head and the essential light chain of the blocked head and between the Leu305-Gln327 interaction loop of the free head and the N-terminal fragment of the RLC of the blocked head. These interactions, added to those previously described, would help switch off the thick filament. Molecular dynamics simulations suggest how phosphorylation could increase the helical content of the RLC N-terminus, weakening these interactions, thus releasing both heads and activating the thick filament.

Tumour necrosis factor (TNF), a cytokine mainly produced by macrophages, is associated with a broad spectrum of biological effects, mainly associated with the host defense against microbes. The TNF gene is located on chromosome six within the major histocompatibility complex (MHC). Rheumatoid arthritis (RA) is a systemic autoimmune disease where TNF plays a central role in its etiology and pathogenesis. Written medical evidence of RA can be traced at least as far back as the 17th century, while human paleopathological studies appear to show the presence of RA prior to this period. The fact that RA has experienced an increment both in severity and mortality could be explained by many causes, particularly the crucial role of the immune system. Single-nucleotide polymorphisms (SNPs) are the most common genetic variations and occur at a frequency of approximately 1 in 1000 bp throughout the genome. The -308 TNF SNP is a mutation that affects the promoter region of the TNF gene. It defines the TNF1 and TNF2 alleles, determining low and high levels of TNF expression, respectively. The presence of the TNF2 allele has also been linked to increased susceptibility to and severity in a variety of autoimmune and inflammatory disorders, including RA, systemic lupus erythematosus, and ankylosing spondylitis. Studies on the functional significance of -308 SNP have detected higher levels of TNF production by cells from TNF2-carrying individuals than cells from TNF1 individuals. This difference does not appear to be due to other genes lying within the MHC region. Since the presence of the TNF2 allele may increase the host's resistance to local infection, by increasing local production of TNF at the infection site, we may suggest that such a mutation has emerged as a selective advantage to carriers of the TNF2 allele. This hypothesis may prove itself by observing the high incidence of tuberculosis and other infectious processes in those patients treated with anti-TNF therapy. Since the human lifespan has increased, the persistence of the TNF2 allele at high frequency in the population now confers what appears to be a marked survival disadvantage. As a result of the disregulation of the immune system, the genetically-predisposed host expresses larger amounts of TNF, leading to chronic inflammatory processes and autoimmune diseases, currently more prevalent. We suggest that RA, a relatively new and increasingly frequent disease, is favored by the presence of the -308 TNF promoter polymorphism, responsible for increased TNF production.

Fibroblasts consist of heterogeneous subpopulations that have distinct roles in fibrotic responses. Previously we reported enhanced proliferation in response to fibrogenic growth factors and selective activation of latent transforming growth factor (TGF)-beta in fibroblasts lacking cell surface expression of Thy-1 glycoprotein, suggesting that Thy-1 modulates the fibrogenic potential of fibroblasts. Here we report that compared to controls Thy-1-/- C57BL/6 mice displayed more severe histopathological lung fibrosis, greater accumulation of lung collagen, and increased TGF-beta activation in the lungs 14 days after intratracheal bleomycin. The majority of cells demonstrating TGF-beta activation and myofibroblast differentiation in bleomycin-induced lesions were Thy-1-negative. Histological sections from patients with idiopathic pulmonary fibrosis demonstrated absent Thy-1 staining within fibroblastic foci. Normal lung fibroblasts, in both mice and humans, were predominantly Thy-1-positive. The fibrogenic cytokines interleukin-1 and tumor necrosis factor-alpha induced loss of fibroblast Thy-1 surface expression in vitro, which was associated with Thy-1 shedding, Smad phosphorylation, and myofibroblast differentiation. These results suggest that fibrogenic injury promotes loss of lung fibroblast Thy-1 expression, resulting in enhanced fibrogenesis.

A total of ten extracts from different parts of eight medicinal plants that are used in the treatment of gastrointestinal disorders, were evaluated to determine their spasmolytic action on in vitro isolated rat ileum. All extracts were less potent than papaverine, which was used as a positive control.

Eighty-eight samples of ground meat were randomly collected from retail stores in the metropolitan area of Monterrey, Mexico, and were analyzed for microbial contamination. Methods were those recommended by the Mexican regulation and/or the U.S. Food and Drug Administration. Over 75% of the samples contained > 10(5) total mesophilic microorganisms per g, and over 40% had >10(6) total coliforms per g. Fecal coliforms were present in most samples. Staphylococcus aureus was detected in 2.3% of the samples, Salmonella spp. in 11.4%, Listeria spp. in 62%, and L. monocytogenes in 16%. Escherichia coli was detected in 76% of samples, but none was serotype O157:H7. Shigella spp. was not found in any sample. Fusarium spp. and Mucor spp. were detected in 3.4% of the samples, and low levels of yeast in 93%. The microbiological quality of the ground meat analyzed was unsatisfactory, and the product could be an important cause of food poisoning.

We produced, selected and cloned hybridomas that secrete monoclonal antibodies against human apolipoprotein (apo) A-I. All of the antibodies corresponded to the IgG(1) subclass and were named 1C11, 2B4, 2C10, 7C5, 8A4 and 8A5. The antibodies were characterized by their reactivity with whole lipoproteins, apolipoproteins, synthetic peptides and fragments generated by cleavage of the apo A-I. Three of the monoclonal antibodies studied (2B4, 2C10 and 7C5) were similarly inhibited by an amino-terminal peptide (amino acid sequence 1-20) of apo A-I, whereas antibodies 1C11, 8A4 and 8A5 had no reaction. Other results show that monoclonal antibody 1C11 recognizes an epitope located between amino acids 135-148. We evaluated the monoclonal antibody 8A4 against different HDL subpopulations by competitive displacement analysis and it showed a similar reactivity with the HDL particles: LpA-I and LpA-I:A-II. This antibody was used to standardize a sandwich ELISA to quantitate LpA-I in plasma. We conclude that these monoclonal antibodies are relevant for the study of apo A-I epitope expression and for quantitating apo A-I containing lipoparticles.

The synthesis of new N3-arylciclohexanespiroimidazolidine-2,4-diones, N3-arylciclohexanespiroimidazolidine-2-tio-4-ones and the 4-hydroxy derivatives is described and their structures discussed on the basis of I.R. and 1H-N.R.M. data. The anthelmintic activity of these compounds was tested.