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Enzymatic nanoreactors were obtained by galactose-1-phosphate uridylyl-transferase (GALT) encapsulation into plant virus capsids by a molecular self-assembly strategy. The aim of this work was to produce virus-like nanoparticles containing GALT for an enzyme-replacement therapy for classic galactosemia. The encapsulation efficiency and the catalytic constants of bio-nanoreactors were determined by using different GALT and virus coat protein ratios. The substrate affinity of nanoreactors was slightly lower than that of the free enzyme; the activity rate was 16 % of the GALT free enzyme. The enzymatic nanoreactors without functionalization were internalized into different cell lines including fibroblast and kidney cells, but especially into hepatocytes. The enzymatic nanoreactors are an innovative enzyme preparation with potential use for the treatment of classic galactosemia., (© 2021 Wiley-VCH GmbH.)

A series of functionalized quinoline-based aromatic oligoamide foldamers were prepared in their two enantiomeric forms, comprising an enantiopure terminal camphanyl chiral inducer, which governed the adjacent (P-/M-) helical-handedness. Hierarchical chirality transfer was further investigated in chromophore-appended variants via a range of electronic and vibrational spectroscopic techniques, including circularly polarized luminescence, vibrational circular dichroism and fluorescence. Intense total and polarized photoluminescence (up to Φ lum =0.39, g lum =1.5×10 -3 ) was observed in the visible region from these modular multicomponent architectures and a significant influence of positional isomerism was evidenced. The optimal position of a fluorophore substituent on the quinoline hexamers was determined as being position 2 over position 6, as stronger chiroptical features were systematically observed with the 2-positioned derivatives., (© 2021 Wiley-VCH GmbH.)

Osteosarcoma is a bone cancer considered rare to humans, but common in dogs. Dogs and humans share genetic homology and environmental risk factors. Improving the treatment of osteosarcoma in dogs could also be relevant to improve procedures in humans. Traditional treatments of osteosarcoma involve surgery and chemotherapy. Such treatments are commonly aggressive and not possible for many patients. Electrochemotherapy emerges as a minimally invasive, effective, and safe treatment alternative. Electrochemotherapy combines applications of high-intensity electric fields during short periods with anti-cancer drugs to improve its medicine cytotoxicity. Analyzing the electric field distribution, as well as electric current density, are essential to electrochemotherapy success. This paper brings the first case of a canine osteosarcoma treatment performed with bleomycin and electrochemotherapy. We performed in silico studies with finite element method software to observe the electric field distribution. In silico experiments help to verify possibilities and limitations of treating bone destruction and macro or micro tumor infiltrations around the primary tumor mass. Results show that both needle or plate electrodes are feasible to remove the tumor even with invasion into the bone. Plate electrodes perform well in treating micro infiltrations when associated with conductive gel and direct contact between electrode and bone (without soft tissues). Needle electrodes are effective in treating tumor infiltration on external cortical bone. Multiple applications are needed to cover all cranium layers with sufficient electric field intensity. Electrochemotherapy protocol with needle or plate electrodes does not present sufficient electric current density capable of affecting brain tissue, even in cases of bone destruction., (© 2020 International Center for Artificial Organs and Transplantation and Wiley Periodicals LLC.)

Morphological characteristics and source of adipose tissue as well as adipokines may increase cardiometabolic risk. This study aimed to explore whether adipose tissue characteristics may impact metabolic and atherogenic risks. Subcutaneous Adipose Tissue (SAT), Visceral Adipose Tissue (VAT) and peripheral blood were obtained from obese patients submitted to bariatric surgery. Adipose tissue (morphometry), plasma adiponectin, TNF-α, resistin (multiplexing) and biochemical chemistry were analyzed; as well as endothelial dysfunction (Flow Mediated Dilation, FMD) and atherogenesis (Carotid Intima Media Thickness, CIMT). Subgroups divided by adipocyte size and source were compared; as well as correlation and multivariate analysis. Sixty patients 36.6% males, aged 44 years-old, BMI 46.7 kg/m 2 were included. SAT's adipocytes showed a lower range of size expandability than VAT's adipocytes. Independent from their source, larger adipocytes were associated with higher glucose, lower adiponectin and higher CIMT. Particularly, larger adipocytes from SAT were associated with higher blood pressure, lower insulin and HDL-cholesterol; and showed positive correlation with glucose, Hb A1c , systolic/diastolic values, and negatively correlated with insulin and adiponectin. VAT's larger adipocytes particularly associated with lower resistin and lower FMD values. Gender and Diabetes Mellitus significantly impacted the relation of adipocyte size/source with the metabolic and atherogenic risk. Multivariable analysis suggested hypertension-resistin-Hb A1c interactions associated with SAT's larger adipocytes; whereas potential insulin-adiponectin associations were observed for VAT's larger adipocytes. Adipocyte morphology and source are differentially related with cardiometabolic and atherogenic risk in population with obesity, which are potentially affected by gender and Diabetes Mellitus.

In recent years, the increase in antimicrobial resistance (AMR) has been recognized as a real threat to human and animal health. It is a problem that has been given the highest priority, uniting nations in the fight against its causes and effects. Among the actions that have been implemented are: clinical and microbiological surveillance, promotion of rational and controlled use of antibiotics, AMR stewardship programs in hospitals, development of tools for rapid diagnosis of infectious diseases to establish prompt and adequate treatment, and radically improving vaccination strategies. The current COVID-19 pandemic has placed disproportionate demands on the healthcare infrastructure and economy worldwide, which will negatively impact on the availability of materials as well as the technical capacity for diagnosis, patient care, and treatment of both COVID-19 and non-COVID-19 patients. Disruptions to production and distribution chains will hamper the availability and usage of antibiotics, also interrupting several of the activities that have been implemented thus far to combat AMR, including detailed laboratory monitoring and reinforced vaccination programs. Here, we discuss the main aspects that should be considered with regard to AMR, that may be affected by the pandemic and propose some actions to counter them., (Copyright © 2020 IMSS. Published by Elsevier Inc. All rights reserved.)

The one-pot cascade reaction of naturally occurring enzymes is exciting for highly selective complex reaction and biodegradable approaches. Tamoxifen is the main drug against breast cancer for decades and induces an anticancerous effect upon metabolic activation by cytochrome P450 (CYP450). Herein, bi-enzymatic nanoreactors (NRs) are developed as a multimodality platform for smart action against breast tumors. CYP BM3 of Bacillus magaterium (CYP) is co-confined with glucose oxidase (GOx) where GOx produces H 2 O 2 in the presence of glucose that elicits the CYP-mediated transformation of tamoxifen. The scintillating and mesoporous LaF 3 :Tb as nanocarrier showed advantages like a wide range of pore size and positive surface charge for efficient loading of enzyme couple, while the smallest pores were available for substrate/product diffusion. The obtained NRs were camouflaged with human serum albumin (HSA) to overcome premature enzyme leaching and provide active stealth properties. The nanocomposite was characterized for physicochemical properties and glucose-mediated sequential catalysis. The in vitro studies demonstrated the cell internalization of NRs in both ER+ and triple-negative breast cancer cell lines and showed significant cytotoxicity. The developed NRs not only improve the outcomes of endocrine therapy in ER+ cells but also synergistically act with oxidation therapy for enhanced therapeutic effect. Importantly, inhibition of triple-negative cells was also achieved. Thus, the development of the new multimodal nanomedicine of the present work should afford new tools towards the theranosis of breast cancer with minimized adverse effects., 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 © 2020 Elsevier Inc. All rights reserved.)

Luminescent lanthanide downconversion nanoparticles (DCNPs) provide a combination of high luminescence intensity, sharp emission peaks with narrow bandwidth and a large Stokes' shift, leading to high-performance biomedical applications mainly for imaging. The purpose of this study is to present a nanotoxicological study of DCNPs Y 2 O 3 codoped with Eu 3+ and functionalized with folic acid (FA). These assessments include cytotoxicity, genotoxicity, hemocompatibility, and in vitro inflammatory studies. We demonstrated by flow cytometry and confocal microscope the internalization of FA-DCNPs in breast cancer and melanoma cells. They were synthesized by sol-gel method and coated with a thin silica shell to make them biocompatible; also they were functionalized with amino groups and FA ligands that bind to the folate receptors (FR) located on the surface of the cancer cells studied. This functionalization enables the DCNPs to be internalized into the cancer cells via endocytosis by the conjugation FA-FR. The DCNPs were characterized with transmission electron microscope, Fourier transform infrared spectroscopy and photoluminescence. The nanotoxicological assessments demonstrated that both nanoparticles (bare and functionalized) are no cytotoxic and no genotoxic at the tested concentrations (0.01-20 μg/mL) in three cell lines (breast, skin cancer, and osteoblasts). Also they are hemocompatible and do not exert nitric oxide production in vitro by macrophages. The FA-DCNPs were clearly localized into the cell cytoplasm with bright red luminescence. Thus, herein we present a complete nanotoxicological study of FA-DCNPs Y 2 O 3 codoped with Eu 3+ and we conclude that these nanoparticles are biocompatible and can be further used for cancer cells bioimaging., (© 2020 Wiley Periodicals, Inc.)

Background: The current study was performed to identify factors that are present at the time of breast cancer (BC) diagnosis that are associated with a higher rate of central nervous system metastasis (CNSm)., Methods: The authors analyzed a database of patients with a confirmed diagnosis of BC who were referred for a neuro-oncology consultation at the National Cancer Institute in Mexico City, Mexico, from June 2009 to June 2017. Information was collected prospectively and included demographic, pathologic, and clinical data at the time of diagnosis of BC. Bivariate and multivariate logistic regression models were built to estimate the associations between the development of CNSm and the time after BC diagnosis., Results: Among 970 patients with BC, 263 (27%) were diagnosed with CNSm. The median time from BC diagnosis to the development of CNSm was 33 months (interquartile range, 15-76 months). After multivariate analysis, age <50 years at the time of BC diagnosis (odds ratio [OR], 2.5; 95% confidence interval [95% CI], 1.8-3.5 [P < .0001]), human epidermal growth factor receptor 2 (HER2)-positive status (HER2+) (OR, 3.6; 95% CI, 2.1-6.1 [P < .0001]), luminal B/HER2+ subtype (OR, 3.1; 95% CI, 1.9-5.3 [P < .001]), triple-negative subtype(OR, 2.4; 95% CI, 1.5-4 [P = .001]), and Karnofsky performance status ≤70 (OR, 6.6; 95% CI, 4.5-9.6 [P < .0001]) were associated with a higher frequency of CNSm. Brain parenchyma was the most common site of CNSm. The median overall survival after a diagnosis of CNSm was 12.2 months (95% CI, 9.3-15.1 months)., Conclusions: CNSm is not uncommon among patients with BC, particularly in those with neurologic symptoms who require neuro-oncology evaluation and are aged <50 years at the time of diagnosis, have HER2+ or triple-negative subtypes, have a poor Karnofsky performance status, and/or have ≥2 non-CNS metastases., (© 2020 American Cancer Society.)

Skin burns and ulcers are considered hard-to-heal wounds due to their high infection risk. For this reason, designing new options for wound dressings is a growing need. The objective of this work is to investigate the properties of poly (ε-caprolactone)/poly (vinyl-pyrrolidone) (PCL/PVP) microfibers produced via electrospinning along with sorbents loaded with Argovit™ silver nanoparticles (Ag-Si/Al 2 O 3 ) as constituent components for composite wound dressings. The physicochemical properties of the fibers and sorbents were characterized using scanning electron microscopy (SEM), differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR) and inductively coupled plasma optical emission spectroscopy (ICP-OES). The mechanical properties of the fibers were also evaluated. The results of this work showed that the tested fibrous scaffolds have melting temperatures suitable for wound dressings design (58-60 °C). In addition, they demonstrated to be stable even after seven days in physiological solution, showing no macroscopic damage due to PVP release at the microscopic scale. Pelletized sorbents with the higher particle size demonstrated to have the best water uptake capabilities. Both, fibers and sorbents showed antimicrobial activity against Gram-negative bacteria Pseudomona aeruginosa and Escherichia coli, Gram-positive Staphylococcus aureus and the fungus Candida albicans . The best physicochemical properties were obtained with a scaffold produced with a PCL/PVP ratio of 85:15, this polymeric scaffold demonstrated the most antimicrobial activity without affecting the cell viability of human fibroblast. Pelletized Ag/Si-Al 2 O 3 -3 sorbent possessed the best water uptake capability and the higher antimicrobial activity, over time between all the sorbents tested. The combination of PCL/PVP 85:15 microfibers with the chosen Ag/Si-Al 2 O 3 -3 sorbent will be used in the following work for creation of wound dressings possessing exudate retention, biocompatibility and antimicrobial activity., Competing Interests: The authors declare no conflict of interest.

Background: The use of antimicrobials and myeloablative chemotherapy regimens has promoted multiresistant microorganisms to emerge as nosocomial pathogens, such as vancomycin-resistant Enterococcus faecium (VREfm). We described a polyclonal outbreak of bloodstream infection caused by Efm in a hemato-oncological ward in Mexico. Our aim was to describe the clonal complex (CC) of the Efm strains isolated in the outbreak in comparison with commensal and environmental isolates. Methodology: Sixty Efm clinical, environmental, and commensal strains were included. We constructed a cladogram and a phylogenetic tree using Vitek and Multilocus sequence typing data, respectively. Results: We reported 20 new sequence types (ST), among which 17/43 clinical isolates belonged to CC17. The predominant ST in the clinical strains were ST757, ST1304, ST412, and ST770. Neither environmental nor commensal isolates belonged to CC17. The phylogeny of our collection shows that the majority of the clinical isolates were different from the environmental and commensal isolates, and only a small group of clinical isolates was closely related with environmental and commensal isolates. The cladogram revealed a similar segregation to that of the phylogeny. Conclusions: We found a high diversity among clinical, environmental, and commensal strains in a group of samples in a single hospital. Highest diversity was found between commensal and environmental isolates.

Multimaterial mechanisms are seen throughout natural organisms across all length scales. The different materials in their bodies, from rigid, structural materials to soft, elastic materials, enable mobility in complex environments. As robots leave the lab and begin to move in real environments, including a range of materials in 3D robotics mechanisms can help robots handle uncertainty and lessen control requirements. For the smallest robots, soft materials combined with rigid materials can facilitate large motions in compact spaces due to the increased compliance. However, integrating various material components in 3D at the microscale is a challenge. We present an approach for 3D microscale multimaterial fabrication using two-photon polymerization. Two materials with three orders of magnitude difference in Young's moduli are printed in consecutive cycles. Integrating a soft elastic material that is capable of more than 200% strain along with a rigid material has enabled the formation of hybrid elements, strongly adhered together, with layer accuracy below 3-μm resolution. We demonstrate a multilink multimaterial mechanism showing large deformation, and a 3D-printed 2-mm wingspan flapping wing mechanism, showing rapid prototyping of complex designs. This fabrication strategy can be extended to other materials, thus enhancing the functionality and complexity of small-scale robots.

Molecular helices based on self-organized aromatic oligoamide foldamers have been designed and prepared in their two enantiomeric forms in order to probe their second-order nonlinear chiroptical properties in solution. The quinoline oligoamides were rationally functionalized by electron-donating and electron-withdrawing groups to afford a gradual increase of the electronic polarization of the helical architectures. Their hyper-Rayleigh scattering (HRS) responses in solution were accordingly assessed, using either linearly polarized or circularly polarized incident light. Both methods allowed us to observe nonlinear optical activity that was quantified, for the first time for molecular systems, through circular differential scattering intensity ratios. The hyper-Rayleigh optical activity study reveals important charge-transfer differences within the aromatic oligomers, depending on the helix handedness and on the extent of electronic polarization induced by the appended substituents. The origin of the enantiomeric difference is discussed considering both achiral and chiral contributions. Overall, using aromatic oligoamide foldamers as a chiral model, we demonstrate the capabilities of HRS as a complementary chiroptical method, ideally suited for the analysis of various chiral molecular and supramolecular systems in solution. The reliability and chiral discrimination sensitivity of the method can be further improved through dynamic measurements using standard polarization modulation and heterodyning techniques.

Objective: To establish the current situation of antimicrobial resistance and antibiotic consumption in Mexican hospitals., Materials and Methods: Antimicrobial susceptibility data from blood and urine isolates were collected. Defined daily dose (DDD) of antibiotic consumption/100 occupied beds (OBD) was calculated., Results: Study period: 2016 and 2017. Of 4 382 blood isolates, E. coli and K. pneumoniae were most frequently reported, with antimicrobial resistance >30% for most drugs tested, only for carbapenems and amikacin resistance were <20%. A. baumannii had antimicrobial resistance >20% to all drugs. Resistance to oxacillin in S. aureus was 20%. From 12 151 urine isolates, 90% corresponded to E. coli; resistance to ciprofloxacin, cephalosporins and trimethoprim/sulfamethoxazole was >50%, with good susceptibility to nitrofurantoin, amikacin and carbapenems. Global median antimicrobial consumption was 57.2 DDD/100 OB., Conclusions: s. This report shows a high antimicrobial resistance level in Gram-negative bacilli and provides an insight into the seriousness of the problem of antibiotic consumption., Competing Interests: Declaration of conflict of interests. The authors declare that they have no conflict of interests.

Introduction: Vertigo is a common condition occurring in the general population and is usually self-limited. Reports studying vertigo in patients with brain metastasis (BM), are scarce. Therefore, the aim of this study was to analyze if the presence of vertigo in cancer patients is associated with the presence of BM., Methods: This study was conducted in a cancer referral center, where patients with confirmed systemic cancer sent for a neuro-oncologic consultation from May 2012 to March 2018 were included for review., Results: Of 3220 patients, 723 were diagnosed with BM, and 204 had vertigo. Of these patients, 22.5% of those who had vertigo were diagnosed to have BM and 6% of those with BM had vertigo as an initial symptom (odds ratio [OR] 0.9; p = 0.9). An additional symptom was present in 104 patients with vertigo. Bivariate regression analysis disclosed a higher risk of having BM in patients with vertigo accompanied by headache (OR18.6; p < 0.0001), ataxia (OR12.1; p < 0.0001), seizures (OR10.9; p = 0.04), visual symptoms (OR10.4; p < 0.0001), speech impairment (OR6.3; p = 0.01), altered mental status (OR7.4; p < 0.0001), and focal weakness (OR7.4; p = 0.001), or focal sensitive complaint (OR6.9; p = 0.003). Vertigo with headache or ataxia remained statistically significant after multivariate analysis., Conclusion: In this cohort, a higher risk of having BM was associated with the presence of vertigo coexistent with headache, ataxia, seizures, visual symptoms, speech impairment, altered mental status, focal weakness, or focal sensitive complaint. On the basis of these results, these accompanying symptoms must be considered as red flags in patients with systemic cancer., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Eighty-three wild and domestic carnivores of nine species from Janos Biosphere Reserve (JBR), Mexico, were tested by serologic and molecular assays to determine exposure and infection rates of carnivore protoparvovirus 1. Overall, 50.8% (33/65) of the wild carnivores and 100% (18/18) of the domestic dogs tested were seropositive for Canine protoparvovirus 1 (CPV), while 23% (15/65) of the wild carnivores and 22.2% (4/18) of the domestic dogs were PCR positive for CPV. Phylogenetic analysis confirmed circulation of CVP-2 with residues 426 Asn (CPV2a = 1/19) and 426 Glu (CPV-2c = 18/19) among carnivores in JBR. The prevalence of both PCR positivity and antibodies to CPV varied significantly among wild host species. Of the six identified haplotypes, three were unique to kit foxes (Vulpes macrotis) (the species with higher haplotype richness) and two to striped skunks (Mephitis mephitis). The remaining haplotype was shared among all carnivore species including dogs suggesting non-host specificity and bidirectional and continuous viral transmission cycle in the JBR. The phylogenetic similarity of CPV strains from dogs and wild carnivores and the higher prevalence of CPV in wild carnivores captured near towns relative to those captured far from towns suggest that dogs might be an important source of CPV infection for wild carnivores in the JBR. We provide evidence that cross-species transmission occurs at the domestic-wildlife interface in JBR.

Quinoline oligoamide foldamers appended with non-chiral fluorophores and derivatized with a camphanyl chiral inducer display strong chiroptical properties at tunable wavelengths as proved by CD and CPL spectroscopies. Induced CPL activity with high luminescence dissymmetry factors was observed in the visible range at wavelengths specific to the fluorophores.

Rationale: Posterior reversible encephalopathy syndrome (PRES) has been associated with the use of several medications, including chemotherapeutic agents., Patient Concerns: A 65-year-old woman was diagnosed with adenocarcinoma of the ovary, after sixth-line treatment with topotecan, at the beginning of the fourth cycle, she was admitted to the emergency room for presenting tonic-clonic seizures, visual disturbance, and hypertension. A 66-year-old woman was diagnosed with bilateral breast cancer; due to disease progression, treatment with paclitaxel and gemcitabine was started, 1 month after the last dose of chemotherapy, she was admitted to the emergency room for suffering severe headache, altered mental status, tonic-clonic seizures, and hypertension. A 60-year-old patient diagnosed with breast cancer on the left side, underwent second-line chemotherapy with gemcitabine, carboplatin, and bevacizumab, and 1 month after the last dose of chemotherapy, she was also admitted to the emergency room due to altered mental status, vomiting, tonic-clonic seizures, and hypertension., Diagnosis: They were diagnosed as PRES based on physical examination, laboratory findings, and imaging techniques that revealed diffuse lesions and edema within the parieto-occipital regions., Interventions: They received support treatment with blood pressure (BP) control, seizures were controlled with a single anti-epileptic agent, and chemotherapeutic agents from the onset of PRES to its resolution were discontinued., Outcomes: All these patients improved after medical treatment was started., Lessons: Medical personnel and therapeutic establishments need to be made aware about this chemotherapy-induced neurologic complication.

The present study describes the discovery of a singular sedimentary structure corresponding to an ichnite that was excavated at the paleo-archaeological site Pilauco (Osorno, Chile). The trace fossil is associated with megafauna bones, plant material and unifacial lithic tools. Here we present a detailed analysis of the Pilauco ichnite and associated sedimentary structures, as well as new radiocarbon data. The ichnological analysis confidently assigns the trace to the ichnospecies Hominipes modernus-a hominoid footprint usually related to Homo sapiens. Some particular characteristics of the Pilauco trace include an elongated distal hallux, lateral digit impressions obliterated by the collapsed sediment, and sediment lumps inside and around the trace. In order to evaluate the origin of the ichnite, trackmaking experiments are performed on re-hydrated fossil bed sediments. The results demonstrate that a human agent could easily generate a footprint morphology equivalent to the sedimentary structure when walking on a saturated substrate. Based on the evidence, we conclude that the trackmaker might well have been a bare-footed adult human. This finding, along with the presence of lithic artifacts in the same sedimentary levels, might represent further evidence for a pre-Clovis South American colonization of northern Patagonia, as originally proposed for the nearby Monte Verde site., Competing Interests: The authors have declared that no competing interests exist.

The current photodynamic therapy (PDT) is majorly hindered by the shallow penetration depth and oxygen dependency, limiting its application to deep-seated solid hypoxic tumors. Thus, it is meaningful to develop efficient X-ray mediated PDT system capable of generating reactive oxygen species (ROS) under both the normoxic and hypoxic conditions. Herein, we report the synthesis and characterization of nanocomposite, YAG:Pr@ZnO@PpIX with an amalgamation of UV-emitting Y 2.99 Pr 0.01 Al 5 O 12 (YAG:Pr) nanoscintillator, and zinc oxide (ZnO) and protoporphyrin IX (PpIX) as photosensitizers. YAG:Pr surface was coated with a ZnO layer (∼10 nm) by atomic layer deposition, and then PpIX was covalently conjugated via a linker to give YAG:Pr@ZnO@PpIX. The photo- and cathodoluminescence analyses gave the evidences of efficient energy transfer from YAG:Pr to ZnO at ∼320 nm, and YAG:Pr@ZnO to PpIX at Soret region (350-450 nm). The nanohybrid was able to produce both, Type I and Type II ROS upon direct and indirect photoactivation with UV 365nm and UV 290nm , respectively. In vitro cytotoxicity of non-activated YAG:Pr@ZnO@PpIX in mouse melanoma cells revealed low toxicity, which significantly enhanced upon photoactivation with UV 365nm indicating the photokilling property of the nanohybrid. Overall, our preliminary studies successfully demonstrate the potential of YAG:Pr@ZnO@PpIX to overcome the limited penetration and oxygen-dependency of traditional PDT., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objectives: One third of infrainguinal vein bypasses may fail within the first 1.5 years. Pro- and anti-inflammatory mechanisms are thought to be involved in these graft stenoses and occlusions. In previous studies, low levels of anti-phosphorylcholine IgM (anti-PC IgM, an innate anti-inflammatory IgM) have been associated with increased cardiovascular events. In this study, the peri-operative dynamics of anti-PC IgM levels were established during leg bypass surgery, and associations assessed between anti-PC IgM levels and primary graft patency., Design and Methods: This was a prospective, observational cohort study of infrainguinal autogenous vein bypass for peripheral arterial occlusive disease involving four university affiliated hospitals. Plasma cytokine and anti-PC IgM levels were measured pre- and post-operatively. The outcome of interest was loss of primary graft patency because of occlusion or intervention for graft stenosis., Results: One hundred and forty-two consecutive patients were enrolled: mean age 66 (46-91); 91% white race and male; 72.5% critical limb ischaemia (Fontaine III or IV). Median pre-operative anti-PC IgM levels were 49 units/mL (IQR 32.3-107.7, mean 89.8 + 101 sd). During follow up of an average of 1.8 years (1 month-7.4 years), 50 (35.2%) grafts lost primary patency. Pre-operative levels of interleukin 6 or C-reactive protein did not predict graft failure. Patients with pre-operative anti-PC IgM values in the lowest quartile had a twofold increased risk of graft failure (multivariable Cox proportional hazard, p = .03, HR 2.11, 95% CI 1.09-4.07), even after accounting for the other significant factors of conduit diameter, distal anastomosis, smoking, and the severity of leg ischaemia., Conclusions: Low levels of anti-PC IgM are associated with vein bypass graft failure. This biological mediator may be a useful marker to identify patients at higher risk, and offers the potential for novel, directed therapies for vascular inflammation and its consequences., (Copyright © 2018 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.)

Electronic pacemakers can treat electrical conduction disorders in hearts; however, they are invasive, bulky, and linked to increased incidence of infection at the tissue-device interface. Thus, researchers have looked to other more biocompatible methods for cardiac pacing or resynchronization, such as femtosecond infrared light pulsing, optogenetics, and polymer-based cardiac patches integrated with metal electrodes. Here we develop a biocompatible nongenetic approach for the optical modulation of cardiac cells and tissues. We demonstrate that a polymer-silicon nanowire composite mesh can be used to convert fast moving, low-radiance optical inputs into stimulatory signals in target cardiac cells. Our method allows for the stimulation of the cultured cardiomyocytes or ex vivo heart to beat at a higher target frequency., Competing Interests: The authors declare no conflict of interest.

Weight Cycling (WC) is a prevalent behavior associated with adverse cardiovascular (CV) health. However, a 2010 review on the effects of WC and blood pressure (BP) determined that there was not enough evidence to draw definitive conclusions. Central BP is the principal predictor of CV risk compared to peripheral BP. The influence that WC may have specifically on central BP is unknown. Cross-sectional observation of self-reported history of WC on measures of CV health was undertaken. Seventy-five women completed a Weight and Lifestyle Inventory questionnaire, which is considered a reliable index of WC ( r  = 0.87, p  < 0.001). Measures of visceral fat, BP, arterial stiffness, and VO 2 peak were taken. Regression equations were used to assess primary predictors of these outcomes. Seventy-five middle aged (39 ± 11 years), obese (32 ± 7 kg/m 2 ), and relatively unfit (24 ± 8 ml·kg -1 min -1 ) women completed the study. Visceral fat was the strongest predictor of brachial systolic blood pressure (SBP; r 2  = 0.283), brachial diastolic blood pressure (DBP; r 2  = 0.176), central SBP ( r 2  = 0.375), and augmentation index (AIx; r 2  = 0.535, all p  < 0.001). VO 2 peak was the strongest predictor of central DBP ( r 2  = 0.062, p  = 0.036) and augmentation pressure (AP; r 2  = 0.491, p  < 0.001). Weight cycling index was associated with visceral fat ( r  = 0.521, p  < 0.001). Visceral fat was a mediator between WC and central SBP (confidence interval [CI] = 0.0053-0.0602), AP (CI = 0.0507-0.4915), AIx (CI = 0.0025-0.0699), and carotid-femoral pulse wave velocity (CI = 0.0115-0.1227; all p  < 0.05). WC may increase visceral fat accumulation, which was associated with increased central SBP and measures of arterial stiffness., Competing Interests: No competing financial interests exist.

Light sheet optical microscopy on strontium aluminate nanoparticles (SrAl 2 O 4 NPs)1 codoped with Eu 2+ and Dy 3+ was used for cancer cell tagging and tracking. The nanoparticles were synthesized by urea-assisted combustion with optimized percentage values of the 2 codoping rare-earth ions for cell viability and for lower cytotoxic effects. The optical properties of these materials showed an excitation wide range of wavelengths (λ exc = 254-460 nm), a broad emission band (λ em = 475-575 nm) with the maximum centered wavelength at 525 nm and a half lifetime within the seconds regime. The feasibility to measure the nanoparticle luminescence under the selective plane illumination configuration was studied by immersing the nanoparticles in 1% Agarose. The potential applicability of the synthesized nanophosphors for cancer cell tagging was demonstrated by using in vitro experiments with human breast adenocarcinoma MCF-7 cells. A single MCF-7 cell observed by the use of light sheet microscopy with UV excitation. The cell has been bio-labeled with FA-SrAl 2 0 4 : Eu 2+ , Dy 3+ NPs and 4',6-diamidino-2-phenylindole, dihydrochloride for nucleus identification., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: Thymoma is the most common mediastinal tumor, representing <1% of all cancers. It is usually associated with paraneoplastic disorders, mainly myasthenia gravis (MG). The aim of the present study was to describe patients with thymoma and the differences between those with MG and those without it., Methods: A retrospective 10-year database of the patients with thymoma treated at a single cancer referral hospital (National Institute of Cancer, Mexico City), was analyzed., Results: Sixty-four files from patients with thymoma were analyzed, 18 of them had MG. The symptoms that occurred most frequently in patients with MG were ptosis, diplopia, appendicular weakness, dysphonia and dysphagia. The most frequent Myasthenia Gravis Foundation of America (MGFA) stage was IIIb followed by stage I. Almost all the patients with MG had positive Acetylcholine Receptor antibodies (P<0.001), with not specified antibodies in four patients. The median overall survival showed a trend to be higher among the patients with MG, but there were no significant differences., Conclusions: In patients with thymoma MG manifests with different clinical and autoimmune traits, but not survival differences. A larger multi-centric study should be encouraged to evaluate the prognostic implications of having MG in patients with thymoma., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Cerebral Cavernomas (CC) are vascular malformations located in the Central Nervous System (CNS) characterized by endothelium-lined vascular channels without parenchyma between them, whose main risk is hemorrhage. The aim of this study is to report adult cancer patients that developed CC after radiotherapy (RT) to the CNS during oncological surveillance., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Plant rhizobacteria have been successfully used as biocontrol agents against fungal phytopathogens. However, their potential to control two important avocado diseases, namely Fusarium dieback (FD) and Phytophthora root rot (PRR), has been poorly studied. FD is an emerging disease triggered by fungi associated with two ambrosia beetle species (Euwallacea fornicatus species complex), while PRR is caused by Phytophthora cinnamomi, a soil-borne oomycete. In the present work, the antifungal activity of bacteria isolated from avocado rhizosphere was tested in dual culture assays against Fusarium euwallaceae, Graphium euwallaceae and Graphium sp., causal agents of FD, and against P. cinnamomi. In 2015, rhizosphere soil samples of FD infested and non-infested avocado trees were collected from a commercial avocado orchard in Escondido, California. In an initial screening, 72 of the 168 assessed bacterial isolates reduced mycelial growth of F. euwallaceae by up to 46%. Eight bacterial isolates showing inhibition percentages larger than 40% were then selected for further antagonism assays against the other fungal pathogens. Five bacterial isolates, determined by 16S rDNA sequencing to belong to the Bacillus subtilis/Bacillus amyloliquefaciens species complex, successfully inhibited the mycelial growth of both Graphium species by up to 30%. The same isolates and an additional isolate identified as Bacillus mycoides, inhibited the growth of P. cinnamomi by up to 25%. This is the first report of avocado rhizobacteria with antifungal activity against pathogens responsible for FD and PRR in avocado.

Purpose: The aim of this study was to determine the prevalence of physical inactivity and its associated factors in adult patients admitted to hospital for noncardiac surgery., Design: Cross-sectional study., Methods: Five hundred able-bodied patients (age ≥45 years) admitted to hospital, also participants in the VISION study, were recruited before noncardiac surgery. The physical activity level (PAL) was assessed with the International Physical of Activity Questionnaire. Logistic regression analysis was conducted to determine the associations between a number of predetermined factors and physical inactivity., Findings: Overall, 59.8% were inactive. Factors associated with inactivity included age, assistance with activities of daily living, and insulin-dependent diabetes., Conclusion: A substantial number of patients scheduled for noncardiac surgery are inactive. Elderly patients, those needing assistance, and those with long-lasting diabetes may benefit from PAL assessment before surgery., Clinical Relevance: Healthcare providers should identify PALs and monitor for known risk factors to prepare patients for surgical procedures.

Introduction: Peripheral and central blood pressures are parameters of arterial stiffness and important cardiovascular risk markers. Today, there are non-invasive methods that measure these pressures., Aim: To validate the non-invasive oscillometric method, compared with invasive pressure measurements obtained by cardiac catheterization., Methods: An open, prospective cohort clinical study in 100 patients, 64 ± 11 years old. The measurement of peripheral and central blood pressures obtained using the Arteriograph ® system oscillometric method, (TensioMed, Budapest-Hungary, Ltd.) was validated in an adult population undergoing simultaneous, contralateral left cardiac catheterization (gold standard) using the radial technique, evaluating the correlation and agreement between the two methods. This study fulfils the latest standardized protocol for central blood pressure validation published by ARTERY Society., Results: The pressures obtained with the Arteriograph ® show a high correlation with the pressures measured using the gold standard. Overall, the intraclass correlation coefficient for brachial pressures was 0.80 (p < 0.001), and 0.91 (p < 0.001) for central pressures. The good agreement between the two methods was demonstrated equally by the Bland-Altman method and independent linear regressions for each variable., Conclusions: The oscillometric noninvasive method employed is easy to use and valid for estimating hemodynamic variables such as central and peripheral arterial pressure, having good agreement and conformity with the gold standard in a different type of patients and conditions. This technique can help optimize cardiovascular assessment in primary and secondary prevention, enhance treatment in selected patients and it could be an important element for future cardiovascular prevention.

Background: Tamoxifen is the standard endocrine therapy for breast cancers, which require metabolic activation by cytochrome P450 enzymes (CYP). However, the lower and variable concentrations of CYP activity at the tumor remain major bottlenecks for the efficient treatment, causing severe side-effects. Combination nanotherapy has gained much recent attention for cancer treatment as it reduces the drug-associated toxicity without affecting the therapeutic response., Results: Here we show the modular design of P22 bacteriophage virus-like particles for nanoscale integration of virus-driven enzyme prodrug therapy and photodynamic therapy. These virus capsids carrying CYP activity at the core are decorated with photosensitizer and targeting moiety at the surface for effective combinatory treatment. The estradiol-functionalized nanoparticles are recognized and internalized into ER+ breast tumor cells increasing the intracellular CYP activity and showing the ability to produce reactive oxygen species (ROS) upon UV 365 nm irradiation. The generated ROS in synergy with enzymatic activity drastically enhanced the tamoxifen sensitivity in vitro, strongly inhibiting tumor cells., Conclusions: This work clearly demonstrated that the targeted combinatory treatment using multifunctional biocatalytic P22 represents the effective nanotherapeutics for ER+ breast cancer.

Understanding the mechanisms responsible for phenotypic diversification, and the associated underlying constraints and ecological factors represents a central issue in evolutionary biology. Mammals present a wide variety of sizes and shapes, and are characterized by a high number of morphological convergences that are hypothesized to reflect similar environmental pressures. Extinct South American notoungulates evolved in isolation from northern mammalian faunas in highly disparate environments. They present a wide array of skeletal phenotypes and convergences, such as ever-growing dentition. Here, we focused on the origins of the rostral diversity of notoungulates by quantifying the shape of 26 genera using three-dimensional geometric morphometric analysis. We tested the influence of allometry and phylogeny on rostral shape and evaluated rates of evolutionary change in the different clades. We found strong allometric and phylogenetic signals concerning the rostral shape of notoungulates. Despite convergent forms, we observed a diffuse diversification of rostral shape, with no significant evidence of influence by large-scaled environmental variation. This contrasts with the increase in dental crown height that occurred in four late-diverging families in response to similar environmental pressures. These results illustrate the importance of considering both biological components and evolutionary rates to better understand some aspects of phenotypic diversity., Competing Interests: We have no competing interests.

The Lower Rio Grande Valley (LRGV) is located on U.S.-Mexican border with a population that is 90% Hispanic [1]. Comprised of Hidalgo, Cameron, Starr and Willacy counties, this region has the highest poverty rate and one of the highest incidences of Type 2 diabetes in the United States [2-4]. Previous studies demonstrated a high prevalence of Human Herpes Virus 8 (HHV8) in the LRGV [5-7]. HHV8 infection has been causally linked to Kaposi Sarcoma (KS) [8]. Here, we retrospectively examine the incidence of KS in the LRGV in a set of HIV-negative Hispanic patients. Strikingly, the incidence of KS was higher in LRGV women compared to the Texas state average (nearly four-fold higher in McAllen-Edinburg-Pharr Metro Statistical Area). This unique profile aligns with the increased HHV8 prevalence in the LRGV, suggesting that HHV8 contributes to a high incidence of HIV-negative KS on the U.S.-Mexican border in Texas., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objective: To determine the frequency of successful aging (SA) and its relationship with frailty in an elderly population., Material and Methods: An analytical cross-sectional study of subjects ≥60 years of age seen as outpatients in a general hospital. Successful aging was defined as scores of ≥ 90 in the Barthel index and ≤ 2 in the Pfeiffer test. Frailty was determined using the Fried criteria., Results: The study included 400 subjects (272 women and 128 men), with a mean age of 71.6±8.2 years. The SA frequency was 40.4%. frail status was statistically higher in non-successful aging subjects than in SA subjects (161.7 versus 7.9%; P<.001). Women were more frequently frail, while being a pensioner/retired and married were associated less frequently with frailty., Conclusions: Successful aging is associated with a lower level of frailty., (Copyright © 2017 SEGG. Publicado por Elsevier España, S.L.U. All rights reserved.)

Objective: This study aimed to evaluate the role of 3 Tesla magnetic resonance imaging in predicting tongue tumour thickness via direct and reconstructed measures, and their correlations with corresponding histological measures, nodal metastasis and extracapsular spread., Methods: A prospective study was conducted of 25 patients with histologically proven squamous cell carcinoma of the tongue and pre-operative 3 Tesla magnetic resonance imaging from 2009 to 2012., Results: Correlations between 3 Tesla magnetic resonance imaging and histological measures of tongue tumour thickness were assessed using the Pearson correlation coefficient: r values were 0.84 (p < 0.0001) and 0.81 (p < 0.0001) for direct and reconstructed measurements, respectively. For magnetic resonance imaging, direct measures of tumour thickness (mean ± standard deviation, 18.2 ± 7.3 mm) did not significantly differ from the reconstructed measures (mean ± standard deviation, 17.9 ± 7.2 mm; r = 0.879). Moreover, 3 Tesla magnetic resonance imaging had 83 per cent sensitivity, 82 per cent specificity, 82 per cent accuracy and a 90 per cent negative predictive value for detecting cervical lymph node metastasis., Conclusion: In this cohort, 3 Tesla magnetic resonance imaging measures of tumour thickness correlated highly with the corresponding histological measures. Further, 3 Tesla magnetic resonance imaging was an effective method of detecting malignant adenopathy with extracapsular spread.

The wide application of silver nanoparticles (AgNPs) has pointed out the need to evaluate their potential risk and toxic effects on human health. Herein, the cytotoxic effects of Argovit™ AgNPs were evaluated on eight cancer cell lines. Further cytotoxic studies were performed in gynecological cancer cell lines from cervical (HeLa) and breast (MDA-MB-231 and MCF7) cancer. In both cases, the half maximal inhibitory concentration (IC 50 ) of AgNPs produced the formation of reactive oxygen species (ROS) after 24 h of incubation, but it was not statistically significant compared with untreated cells. However, HeLa, MDA-MB-231, and MCF7 cells treated with the maximal IC of AgNPs induced the formation of ROS either at 12 or 24 h of incubation. Genotoxicity achieved by comet assay in HeLa, MDA-MB-231, and MCF7 cells revealed that exposure to IC 50 of AgNPs does not induced noticeable DNA damage in the cells. However, the IC of AgNPs provoked severe DNA damage after 12 and 24 h of exposure. We conclude that, Argovit (polyvinylpyrrolidone-coated AgNPs) induce a cytotoxic effect in a time and dose-dependent manner in all the eight cancer cell lines tested. Nevertheless, the genotoxic effect is mainly restricted by the concentration effect. The results contribute to explore new therapeutic applications of AgNPs for malignances in murine models and to study in deep the cytotoxic and genotoxic effects of AgNPs in healthy cells at the surrounding tissue of the neoplasia.

Currently, nanomaterials are more frequently in our daily life, specifically in biomedicine, electronics, food, textiles and catalysis just to name a few. Although nanomaterials provide many benefits, recently their toxicity profiles have begun to be explored. In this work, the toxic effects of silver nanoparticles (35nm-average diameter and Polyvinyl-Pyrrolidone-coated) on biological systems of different levels of complexity was assessed in a comprehensive and comparatively way, through a variety of viability and toxicological assays. The studied organisms included viruses, bacteria, microalgae, fungi, animal and human cells (including cancer cell lines). It was found that biological systems of different taxonomical groups are inhibited at concentrations of silver nanoparticles within the same order of magnitude. Thus, the toxicity of nanomaterials on biological/living systems, constrained by their complexity, e.g. taxonomic groups, resulted contrary to the expected. The fact that cells and virus are inhibited with a concentration of silver nanoparticles within the same order of magnitude could be explained considering that silver nanoparticles affects very primitive cellular mechanisms by interacting with fundamental structures for cells and virus alike., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Most of the drugs used in chemotherapy should be activated by a transformation catalyzed by cytochrome P450 (CYP) enzymes. In this work, bacteriophage P22 virus-like particles (VLPs) containing CYP activity, immunologically inert and functionalized in order to be recognized by human cervix carcinoma cells and human breast adenocarcinoma cells were designed. The CYP was encapsulated inside the virus capsid obtained from the bacteriophage P22. CYP and coat protein were both heterologously expressed in E. coli. The VLPs with enzymatic activity were covered with polyethylene glycol that was functionalized in its distal end with folic acid in order to be recognized by folate receptors exhibited on tumor cells. The capacity of biocatalytic VLPs to be recognized and internalized into tumor cells is demonstrated. The VLP-treated cells showed enhanced capacity for the transformation of the pro-drug tamoxifen, which resulted in an increase of the cell sensitivity to this oncological drug. In this work, the potential use of biocatalytic VLPs vehicles as a delivery system of medical relevant enzymes is clearly demonstrated. In addition to cancer treatment, this technology also offers an interesting platform as nano-bioreactors for intracellular delivery of enzymatic activity for other diseases originated by the lack of enzymatic activity., (Copyright © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Cancer is still a growing public health problem, especially breast cancer that is one of the most important cancers in women. Chemotherapy, even though a successful treatment, is accompanied by severe side effects. Moreover, most of the drugs used for chemotherapy are administered as prodrugs and need to be transformed to the active form by cytochromes P450 (CYPs). In addition, increasing numbers of cancer tissues show lower CYP activity than the surrounding healthy tissues in which prodrugs are preferentially activated causing cytotoxicity. Here, the design of a functionalized cytochrome P450 bioconjugate is reported as nanovehicle for the enzyme direct delivery to the tumor tissue in order to improve the local drug activation. MCF-7 breast cancer cells are treated with CYP-polyethylene glycol bioconjugate functionalized folic acid, where it activates the prodrug tamoxifen and significantly reduces the dose of tamoxifen needed to kill the tumor cells. The CYP bioconjugate covered with polyethylene glycol shows no immunogenic activity. The advantages of increasing the site-specific CYP activity in tumor tissues are discussed., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: Enterococcus faecium causes bloodstream infection (BSI) in patients with hematologic malignancies (HMs). We studied the clinical features and outcomes of patients with HM with vancomycin-sensitive E faecium (VSE) and vancomycin-resistant E faecium (VRE) BSI and determined the genetic relatedness of isolates and circumstances associated with the upsurge of E faecium BSI., Methods: Case-control study of patients with HM and E faecium-positive blood culture from January 2008-December 2012; cases were patients with VRE and controls were VSE isolates. The strains were tested for Van genes by polymerase chain reaction amplification and we performed pulsed-field gel electrophoresis to determine genetic relatedness., Results: Fifty-eight episodes of E faecium BSI occurred: 35 sensitive and 23 resistant to vancomycin. Mortality was 46% and 57%, attributable 17% and 40%, respectively. Early stage HM was associated with VSE (P = .044), whereas an episode of BSI within the 3 months before the event (P = .039), prophylactic antibiotics (P = .013), and vancomycin therapy during the previous 3 months (P = .001) was associated with VRE. The VanA gene was identified in 97% of isolates studied. E faecium isolates were not clonal., Conclusions: E faecium BSI was associated with high mortality. This outbreak of VRE was not clonal; it was associated with antibiotic-use pressure and highly myelosuppressive chemotherapy., (Copyright © 2017 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

The host-parasite-vector relationship of Bartonella spp. system in wild carnivores and their fleas from northwestern Mexico was investigated. Sixty-six carnivores belonging to eight species were sampled, and 285 fleas belonging to three species were collected during spring (April-May) and fall (October-November) seasons. We detected Bartonella species in 7 carnivores (10.6%) and 27 fleas (9.5%) through either blood culture or PCR. Of the 27 Bartonella-positive fleas, twenty-two were Pulex simulans, three were Pulex irritans and one was Echidnophaga gallinacea. The gltA gene and ITS region sequences alignment revealed six and eight genetic variants of Bartonella spp., respectively. These variants were clustered into Bartonella rochalimae, Bartonella vinsonii subsp. berkhoffii and another genotype, which likely represents a novel species of Bartonella spp. Although experimental infection studies are required to prove the vector role of P. simulans, our results suggest that this flea may play an important role in the Bartonella transmission. The results indicated possible host-specific relationships between Bartonella genotypes and the families of the carnivores, but further studies are needed to verify this finding. The presence of zoonotic species of Bartonella spp. in wild carnivores raises the issue of their potential risk for humans in fragmented ecosystems.

White spot syndrome virus (WSSV) is highly lethal and contagious in shrimps; its outbreaks causes an economic crisis for aquaculture. Several attempts have been made to treat this disease; however, to date, there is no effective cure. Because of their antimicrobial activities, silver nanoparticles (AgNPs) are the most studied nanomaterial. Although the antiviral properties of AgNPs have been studied, their antiviral effect against viral infection in aquaculture has not been reported. The AgNPs tested herein are coated with polyvinylpyrrolidone (PVP) and possess multiple international certifications for their use in veterinary and human applications. The aim of this work was to evaluate the survival rate of juvenile white shrimps (Litopenaeus vannamei) after the intramuscular administration of AgNPs. For this, different concentrations of metallic AgNPs and PVP alone were injected into the organisms. After 96 h of administration, shrimp survival was more than 90% for all treatments. The oxygen consumption routine rate and total hemocyte count remained unaltered after AgNP injection, reflecting no stress caused. We evaluated whether AgNPs had an antiviral effect in shrimps infected with WSSV. The results revealed that the survival rate of WSSV-infected shrimps after AgNP administration was 80%, whereas the survival rate of untreated organisms was only 10% 96 h after infection. These results open up the possibility to explore the potential use of AgNPs as antiviral agents for the treatment of diseases in aquaculture organisms, particularly the WSSV in shrimp culture., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

More evidence is needed that links the diagnosis of different congenital heart diseases (CHD) identified after birth, with intermediate altitudes above sea level in geographically and ethnically diverse populations. Our aim was to estimate relative frequencies of CHD diagnosis by altitude and gender in the pediatric population of 12 cities in Colombia. This was a cross-sectional study based on the information collected between 2008 and 2013 in Colombia, during annual congenital heart disease (CHD) case detection campaigns in the post-natal period. All children underwent physical examination, pulse-oximetry, and echocardiography. The odds ratio (OR) was used as the summary statistic to assess associations with altitude in the relative frequency of CHD diagnosis. Data from 5900 children who attended the campaigns were evaluated (54.3 % male), out of which 3309 (56.1 %) were diagnosed with CHD. There were statistically significant differences in the relative distribution of the different CHD by city altitude and gender (p < 0.0001). When compared with sea level, altitudes between 1285 and 3000 m above sea level were associated with increased Patent Ductus Arteriosus (PDA) (ORmh 1.68, 95 % CI 1.34-2.09; p < 0.0001) and left ventricular outflow tract obstruction (LVOTO) diagnoses (ORmh 2.06, 95 % CI 1.63-2.61; p < 0.0001), while the opposite was true for right ventricular outflow tract (RVOTO) diagnosis (OR 0.60; 95 % CI 0.49-0.74, p < 0.0001). These associations were not modified by gender differences. In a geographically and ethnically diverse population, altitudes between 1285 and 3000 m above sea level carried an independent and clinically important excess diagnostic risk of PDA and of LVOTO, when compared to all other CHD.

Ecological factors such as habitat and food availability affect the social structure of bottlenose dolphins ( Tursiops spp.). Here, we describe the social structure of bottlenose dolphins ( T. truncatus ) in Golfo Dulce, Costa Rica, a semi-enclosed, fjord-like tropical embayment resembling a pelagic system. We also examine behaviour-linked social strategies by comparing social structure relative to behavioural state: feeding versus non-feeding. We analysed 333 sightings over 210 days from boat-based surveys. Despite the uniqueness of the area, the 47 analysed adults had a social structure similar to other populations: a well-differentiated fission-fusion society with sex-specific patterns of associations and aggression. These results indicate that differences in social structure relative to other populations were a matter of degree. Association strength of dyads was highly correlated across behavioural states, indicating constraints on social fluidity. Males displayed a marked difference in lagged association rate and females displayed a small difference in association homogeneity between states. We suggest this difference in population-wide social connections between behavioural states, particularly for males, was due to mating strategies, a pressure which is strongest during non-feeding behaviour and relaxed during feeding. This finding highlights the importance of considering behavioural state when examining individual bonds and the behavioural plasticity for which the bottlenose dolphin is well known.

In this study, luminescent upconversion nanoparticles (UCNPs) Y 2 O 3 and Gd 2 O 3 co-doped with Yb 3+ and Er 3+ were prepared by the sol-gel method (SG). These NPs are able to absorb near infrared photons and upconvert them into visible radiation with a direct application in bioimaging, as an important tool to diagnose and visualize cancer cells. The UCNPs were coated with a thin silica shell and functionalized with amino groups for further folic acid conjugation to allow their interaction with folate ligands on the cell surface. Their physical properties were analysed by Transmission Electron Microscopy (TEM), Fourier transform infrared spectroscopy (FTIR) and photoluminescence (PL) measurements. The PL results revealed excellent luminescence properties on all core-shell UCNPs. Cytotoxicity experiments with concentrations of bare and aminosilane coated/functionalized UCNPs between 0.001 μg/mL to 1 μg/mL were tested on two different cell lines from human cervix carcinoma (HeLa) and human colorectal adenocarcinoma (DLD-1) with a colorimetric assay based on the reduction of MTT reagent (methy-134-thiazolyltetrazolium). The assays show that some concentrations of bare UCNPs were cytotoxic for cervical adenocarcinoma cells (HeLa); however, for human colorectal adenocarcinoma all UCNPs are non-cytotoxic. After UCNPs functionalization with silica-aminosilane (APTES/TEOS), all of the nanoparticles tested were found to be non-cytotoxic for both cell lines. The UCNPs functionalized in this work can be further conjugated with specific ligands and used as biolabels for detection of cancer cells.

Purpose: The purpose of this study was to identify the prevalence of xerostomia and related factors among low-income older adults in South Korea., Study Design: A cross-sectional, population-based study., Methods: Using data from the Home Healthcare Service Project, a population-based interview survey with home healthcare service, a total of 9,840 adults 65 years of age and older were assessed for the presence of xerostomia in association with aspects of health lifestyles, chronic disease, oral conditions, and oral function., Results: Overall, 40% of participants reported experiencing xerostomia. Multivariate regression analysis indicated xerostomia was more likely to be reported by women having symptoms of gingival bleeding/pain, having difficulty swallowing liquid or chewing solid food, and having multiple chronic diseases. Interestingly, older adults who live alone and drink alcohol (two or more times per week) reported fewer problems with xerostomia., Conclusions: Increased focus on the detrimental health consequences of xerostomia would make treatment a higher priority. Improved assessment of at-risk populations, particularly among the elderly, could lead to earlier preventative interventions, lessening the negative impact on quality of life., Clinical Relevance: Health professionals along with the general public need increased knowledge about the detrimental effects of xerostomia on overall health. There is a need for earlier assessment and treatment to facilitate optimal health promotion and disease prevention., (© 2015 Sigma Theta Tau International.)

The ability of poly(ethylene glycol) (PEG) to protect enzymatic peroxidase activity was determined for horseradish peroxidase (HRP), versatile peroxidase (VP), commercial Coprinus peroxidase (BP), and chloroperoxidase (CPO). The operational stability measured as the total turnover number was determined for the four peroxidases. The presence of PEG significantly increased the operational stability of VP and HRP up to 123 and 195%, respectively, and dramatically increased the total turnover number of BP up to 597%. Chloroperoxidase was not protected by PEG, which may be due to the different oxidation mechanism, in which the oxidation is mediated by hypochlorous ion instead of free radicals as in the other peroxidases. The presence of PEG does not protect the enzyme when incubated only in the presence of H2O2 without reducing substrate. The catalytic constants (k cat) are insensitive to the presence of PEG, suggesting that the protection mechanism is not due to a competition between the PEG and the substrate as electron donors. On the other hand, PEG showed to have a significant antioxidant capacity. Thus, we conclude that the protection mechanism for peroxidases of PEG is based in its antioxidant capacity with which it is able scavenge or drain radicals that are harmful to the protein.

Background: The intracellular delivery of enzymes for therapeutic use has a promising future for the treatment of several diseases such as genetic disorders and cancer. Virus-like particles offer an interesting platform for enzymatic delivery to targeted cells because of their great cargo capacity and the enhancement of the biocatalyst stability towards several factors important in the practical application of these nanoparticles., Results: We have designed a nano-bioreactor based on the encapsulation of a cytochrome P450 (CYP) inside the capsid derived from the bacteriophage P22. An enhanced peroxigenase, CYPBM3, was selected as a model enzyme because of its potential in enzyme prodrug therapy. A total of 109 enzymes per capsid were encapsulated with a 70 % retention of activity for cytochromes with the correct incorporation of the heme cofactor. Upon encapsulation, the stability of the enzyme towards protease degradation and acidic pH was increased. Cytochrome P450 activity was delivered into Human cervix carcinoma cells via transfecting P22-CYP nanoparticles with lipofectamine., Conclusion: This work provides a clear demonstration of the potential of biocatalytic virus-like particles as medical relevant enzymatic delivery vehicles for clinical applications.

The mechanisms of industrial dye transformation by versatile peroxidase were elucidated. Purified versatile peroxidase from Bjerkandera adusta was able to decolorize different classes of dyes including azo and phthalocyanines, but unable to transform any of the anthraquinones tested. Kinetic constants for selected dyes were determined and the transformation products were analyzed by EPR spectroscopy and mass spectrometry. The EPR and MS analyses of the enzymatic decolorization products showed the cleavage of the azo bond in azo dyes and the total disruption of the phthalocyaninic ring in phthalocyanine dyes. The EPR analysis on two copper-containing dyes, reactive violet 5 (azo) and reactive blue 72 (phthalocyanine), showed that the transformation can or not break the metal-ion coordination bond according the dye nature. The role of the catalytic Trp172 in the dye transformation by a long-range electron transfer pathway was confirmed and the oxidation mechanisms are proposed and discussed.

Purpose: VEGFR2 tyrosine kinase inhibition (TKI) is a valuable treatment approach for patients with metastatic renal cell carcinoma (RCC). However, resistance to treatment is inevitable. Identification of novel targets could lead to better treatment for patients with TKI-naïve or -resistant RCC., Experimental Design: In this study, we performed transcriptome analysis of VEGFR TKI-resistant tumors in a murine model and discovered that the SPHK-S1P pathway is upregulated at the time of resistance. We tested sphingosine-1-phosphate (S1P) pathway inhibition using an anti-S1P mAb (sphingomab), in two mouse xenograft models of RCC, and assessed tumor SPHK expression and S1P plasma levels in patients with metastatic RCC., Results: Resistant tumors expressed several hypoxia-regulated genes. The SPHK1 pathway was among the most highly upregulated pathways that accompanied resistance to VEGFR TKI therapy. SPHK1 was expressed in human RCC, and the product of SPHK1 activity, S1P, was elevated in patients with metastatic RCC, suggesting that human RCC behavior could, in part, be due to overproduction of S1P. Sphingomab neutralization of extracellular S1P slowed tumor growth in both mouse models. Mice bearing tumors that had developed resistance to sunitinib treatment also exhibited tumor growth suppression with sphingomab. Sphingomab treatment led to a reduction in tumor blood flow as measured by MRI., Conclusions: Our findings suggest that S1P inhibition may be a novel therapeutic strategy in patients with treatment-naïve RCC and also in the setting of resistance to VEGFR TKI therapy., (©2015 American Association for Cancer Research.)

Tuberculosis is a disease caused by the Mycobacterium tuberculosis complex (MTb). In 2011, global mortality due to tuberculosis was 1·4 million individuals. The only available vaccine is the attenuated M. bovis [bacillus Calmette-Guérin (BCG)] strain, which confers variable protection against pulmonary tuberculosis. Some widely distributed non-tuberculous mycobacteria (NTM), such as M. avium and M. arupense, are also potential pathogens for humans. This work aimed to produce and characterize monoclonal antibodies against the M. bovis BCG Mexico strain of the MTb, M. avium subs. hominissuis and the M. arupense strain from NTM. Hybridomas were produced from splenocytes of BALB/c female mice immunized with radiation-inactivated mycobacteria, and the immunoglobulin (Ig)G2a antibody-producing clones with the highest antigenic recognition were selected. The selected clones, Mbv 2A10 for M. bovis BCG Mexico, Mav 3H1 for M. avium and Mar 2D10 for M. arupense, were used in further studies. Enzyme-linked immunosorbent assay (ELISA) and immune proteomics analyses characterized the clones as having the highest cross-reactivity with mycobacteria. Using mass spectrometry, a number of proteins recognized by the monoclonal antibody (mAb) clones were identified. These proteins had roles in metabolic processes, hypoxia, cell cycle and dormancy. In addition, a Clustal W and Immune Epitope Database (IEDB) in-silico analysis was performed in protein sequences that result in the conserved regions within probability epitopes that could be recognized for Mbv2A10 and Mav3H1 clones., (© 2014 British Society for Immunology.)