Improved LINE-1 Detection through Pattern Matching by Increasing Probe Length.

Long Interspersed Element-1 (LINE-1 or L1) is an autonomous transposable element that accounts for 17% of the human genome. Strong correlations between abnormal L1 expression and diseases, particularly cancer, have been documented by numerous studies. L1PD (LINE-1 Pattern Detection) had been previously created to detect L1s by using a fixed pre-determined set of 50-mer probes and a pattern-matching algorithm. L1PD uses a novel seed-and-pattern-match strategy as opposed to the well-known seed-and-extend strategy employed by other tools. This study discusses an improved version of L1PD that shows how increasing the size of the k-mer probes from 50 to 75 or to 100 yields better results, as evidenced by experiments showing higher precision and recall when compared to the 50-mers. The probe-generation process was updated and the corresponding software is now shared so that users may generate probes for other reference genomes (with certain limitations). Additionally, L1PD was applied to other non-human genomes, such as dogs, horses, and cows, to further validate the pattern-matching strategy. The improved version of L1PD proves to be an efficient and promising approach for L1 detection.

Wildfire smoke knows no borders: Differential vulnerability to smoke effects on cardio-respiratory health in the San Diego-Tijuana region.

Exposure to fine particles in wildfire smoke is deleterious for human health and can increase cases of cardio-respiratory illnesses and related hospitalizations. Neighborhood-level risk factors can increase susceptibility to environmental hazards, such as air pollution from smoke, and the same exposure can lead to different health effects across populations. While the San Diego-Tijuana border can be exposed to the same wildfire smoke event, socio-demographic differences may drive differential effects on population health. We used the October 2007 wildfires, one the most devastating wildfire events in Southern California that brought smoke to the entire region, as a natural experiment to understand the differential effect of wildfire smoke on both sides of the border. We applied synthetic control methods to evaluate the effects of wildfire smoke on cardio-respiratory hospitalizations in the Municipality of Tijuana and San Diego County separately. During the study period (October 11th- October 26th, 2007), 2009 hospital admissions for cardio-respiratory diseases occurred in San Diego County while 37 hospital admissions were reported in the Municipality of Tijuana. The number of cases in Tijuana was much lower than San Diego, and a precise effect of wildfire smoke was detected in San Diego but not in Tijuana. However, social drivers can increase susceptibility to environmental hazards; the poverty rate in Tijuana is more than three times that of San Diego. Socio-demographics are important in modulating the effects of wildfire smoke and can be potentially useful in developing a concerted regional effort to protect populations on both sides of the border from the adverse health effects of wildfire smoke.

Microplastic abundance in feces of lagomorphs in relation to urbanization.

The presence of microplastics (MPs) in marine environments has been extensively documented. However, studies of terrestrial species are scarce. Fecal samples (105) of lagomorphs were collected at sites with different levels of urbanization in the Baja California Chaparral and analyzed to quantify and characterize MPs found in the feces. The lagomorph species recorded in the study area are the desert cottontail rabbit (Sylvilagus audubonii), brush rabbit (Sylvilagus bachmani), and black-tailed jackrabbit (Lepus californicus), which play important roles in the food web of the chaparral ecosystem. Microplastics were identified using attenuated total reflectance Fourier transform infrared spectroscopy. Microplastics were detected in 49 % of the samples, with fibers being the dominant shape found (72 %). Most (75 %) of the MPs were <1 mm in size, with a mean length of 0.93 ± 0.99 mm (median 0.60 mm, range 0.02 - <5 mm). Polyamide was the dominant polymer (54 %), indicating that MPs are likely derived from textiles; polyethylene was also abundant (27 %). A difference was also observed in the abundance of MPs in feces from sites with different levels of urbanization, with the highest abundance in feces from the urban sites.

Lung Models to Evaluate Silver Nanoparticles' Toxicity and Their Impact on Human Health.

Nanomaterials (NMs) solve specific problems with remarkable results in several industrial and scientific areas. Among NMs, silver nanoparticles (AgNPs) have been extensively employed as drug carriers, medical diagnostics, energy harvesting devices, sensors, lubricants, and bioremediation. Notably, they have shown excellent antimicrobial, anticancer, and antiviral properties in the biomedical field. The literature analysis shows a selective cytotoxic effect on cancer cells compared to healthy cells, making its potential application in cancer treatment evident, increasing the need to study the potential risk of their use to environmental and human health. A large battery of toxicity models, both in vitro and in vivo, have been established to predict the harmful effects of incorporating AgNPs in these numerous areas or those produced due to involuntary exposure. However, these models often report contradictory results due to their lack of standardization, generating controversy and slowing the advances in nanotoxicology research, fundamentally by generalizing the biological response produced by the AgNP formulations. This review summarizes the last ten years' reports concerning AgNPs' toxicity in cellular respiratory system models (e.g., mono-culture models, co-cultures, 3D cultures, ex vivo and in vivo). In turn, more complex cellular models represent in a better way the physical and chemical barriers of the body; however, results should be used carefully so as not to be misleading. The main objective of this work is to highlight current models with the highest physiological relevance, identifying the opportunity areas of lung nanotoxicology and contributing to the establishment and strengthening of specific regulations regarding health and the environment.

Comparative genomics of Acinetobacter baumannii and therapeutic bacteriophages from a patient undergoing phage therapy.

In 2016, a 68-year-old patient with a disseminated multidrug-resistant Acinetobacter baumannii infection was successfully treated using lytic bacteriophages. Here we report the genomes of the nine phages used for treatment and three strains of A. baumannii isolated prior to and during treatment. The phages used in the initial treatment are related, T4-like myophages. Analysis of 19 A. baumannii isolates collected before and during phage treatment shows that resistance to the T4-like phages appeared two days following the start of treatment. We generate complete genomic sequences for three A. baumannii strains (TP1, TP2 and TP3) collected before and during treatment, supporting a clonal relationship. Furthermore, we use strain TP1 to select for increased resistance to five of the phages in vitro, and identify mutations that are also found in phage-insensitive isolates TP2 and TP3 (which evolved in vivo during phage treatment). These results support that in vitro investigations can produce results that are relevant to the in vivo environment.

Polyphosphazene-Based Nanocarriers for the Release of Camptothecin and Epirubicin.

The design and study of efficient polymer-based drug delivery systems for the controlled release of anticancer drugs is one of the pillars of nanomedicine. The fight against metastatic and invasive cancers demands therapeutic candidates with increased and selective toxicity towards malignant cells, long-term activity and reduced side effects. In this sense, polyphosphazene nanocarriers were synthesized for the sustained release of the anticancer drugs camptothecin (CPT) and epirubicin (EPI). Linear poly(dichloro)phosphazene was modified with lipophilic tocopherol or testosterone glycinate, with antioxidant and antitumor activity, and with hydrophilic Jeffamine M1000 to obtain different polyphosphazene nanocarriers. It allowed us to encapsulate the lipophilic CPT and the more hydrophilic EPI. The encapsulation process was carried out via solvent exchange/precipitation, attaining a 9.2-13.6 wt% of CPT and 0.3-2.4 wt% of EPI. CPT-loaded polyphosphazenes formed 140-200 nm aggregates in simulated body physiological conditions (PBS, pH 7.4), resulting in an 80-100-fold increase of CPT solubility. EPI-loaded polyphosphazenes formed 250 nm aggregates in an aqueous medium. CPT and EPI release (PBS, pH 7.4, 37 °C) was monitored for 202 h, being almost linear during the first 8 h. The slow release of testosterone and tocopherol was also sustained for 150 h in PBS (pH 7.4 and 6.0) at 37 °C. The co-delivery of testosterone or tocopherol and the anticancer drugs from the nanocarriers was expected. Cells of the human breast cancer cell line MCF-7 demonstrated good uptake of anticancer-drug-loaded nanocarriers after 6 h. Similarly, MCF-7 spheroids showed good uptake of the anticancer-drug-loaded aggregates after 72 h. Almost all anticancer-drug-loaded polyphosphazenes exhibited similar or superior toxicity against MCF-7 cells and spheroids when compared to raw anticancer drugs. Additionally, cell-cycle arrest in the G2/M phase was increased in response to the drug-loaded nanocarriers. Almost no toxicity of anticancer-drug-loaded aggregates against primary human lung fibroblasts was observed. Furthermore, the aggregates displayed no hemolytic activity, which is in contrast to the parent anticancer drugs. Consequently, synthesized polyphosphazene-based nanocarriers might be potential nanomedicines for chemotherapy.

Self-Assembled Silk Fibroin-Based Aggregates for Delivery of Camptothecin.

A water-soluble hydrolysate of silk fibroin (SF) (~30 kDa) was esterified with tocopherol, ergocalciferol, and testosterone to form SF aggregates for the controlled delivery of the anticancer drug camptothecin (CPT). Elemental analysis and 1H NMR spectroscopy showed a degree of substitution (DS) on SF of 0.4 to 3.8 mol %. Yields of 58 to 71% on vitamins- and testosterone-grafted SF conjugates were achieved. CPT was efficiently incorporated into the lipophilic core of SF aggregates using a dialysis-precipitation method, achieving drug contents of 6.3-8.5 wt %. FTIR spectra and DSC thermograms showed that tocopherol- and testosterone-grafted SF conjugates predominantly adopted a ß-sheet conformation. After the esterification of tyrosine residues on SF chains with the vitamin or testosterone, the hydrodynamic diameters almost doubled or tripled that of SF. The zeta potential values after esterification increased to about -30 mV, which favors the stability of aggregates in aqueous medium. Controlled and almost quantitative release of CPT was achieved after 6 days in PBS at 37 °C, with almost linear release during the first 8 h. MCF-7 cancer cells exhibited good uptake of CPT-loaded SF aggregates after 6 h, causing cell death and cell cycle arrest in the G2/M phase. Substantial uptake of the CPT-loaded aggregates into MCF-7 spheroids was shown after 3 days. Furthermore, all CPT-loaded SF aggregates demonstrated superior toxicity to MCF-7 spheroids compared with parent CPT. Blank SF aggregates induced no hemolysis at pH 6.2 and 7.4, while CPT-loaded SF aggregates provoked hemolysis at pH 6.2 but not at pH 7.4. In contrast, parent CPT caused hemolysis at both pH tested. Therefore, CPT-loaded SF aggregates are promising candidates for chemotherapy.

Enfermedad de Caroli: a propósito de un caso / Carolis disease: report of one case

Resumen La enfermedad de Caroli es una rara patología caracterizada por la existencia de dilataciones saculares segmentarias del árbol biliar intrahepático, que, por lo general, afectan a todo el parénquima hepático, aunque es poco frecuente el compromiso biliar extrahepático. Presentamos el caso de un varón que ingresó con un cuadro clínico de 45 días de evolución, consistente en ictericia colestásica, baja ponderal y prurito. La colangiorresonancia informó múltiples dilataciones saculares en las vías biliares intrahepáticas.

Abstract Caroli disease is a condition characterized by cystic dilatation of the intrahepatic biliary tree that usually affects the entire liver parenchyma, although extrahepatic biliary involvement is rare. The following is the case of a male patient who was admitted due to cholestatic jaundice, low weight, and pruritus for 45 days. Magnetic resonance cholangiopancreatography reported multiple cystic dilatations in the intrahepatic bile ducts.

Polyphosphazene-based nanocarriers for the release of agrochemicals and potential anticancer drugs.

The synthesis and characterisation of novel polyphosphazene nanocarriers, based on hydrophilic polyalkylene oxide Jeffamine M1000 and hydrophobic steroids with a glycinate linker for pH-controlled release of diosgenin and two brassinosteroids (DI31 and S7) with agrochemical and potential anticancer activity, is hereby described. Polyphosphazenes carrying approximately 17 wt% of DI31 or S7 self-assembled in water to form 120-150 nm nanoaggregates, which showed an excellent plant growth effect on radish cotyledons due to sustained delivery of approximately 30% of the agrochemicals after 4 days. Cytotoxic evaluation showed that all polymers carrying steroids and Jeffamine M1000 resulted in strong to moderate toxicity to MCF-7 cancer cells and were non-toxic to primary human lung fibroblast cells at 0.1 to 0.025 mg mL-1. Thus, DI31 and S7 bearing polymers applied at 10-4 to 10-6 mg mL-1 for delivery of recommended DI31 or S7 quantities to crops should be harmless to humans. Particularly, DI31 and S7 bearing polymers with strong cytotoxicity on MCF-7 and non-toxicity on primary human lung fibroblasts, good cell uptake after 6 hours, proper hydrodynamic sizes between 100 and 200 nm, and slow sustained release of cytotoxic drugs (DI31, S7) in acidic conditions might potentiate their accumulation in cancer tissues with good antitumour effects and minor side effects. These results demonstrated that preparation of brassinosteroid bearing polymers is a promising strategy for the preparation of better agrochemicals with reduced pollutant impact on sustainable agriculture and potential anticancer formulations based on analogues of brassinosteroids.

Successful Treatment of Antibiotic-resistant, Poly-microbial Bone Infection With Bacteriophages and Antibiotics Combination.

A patient with a trauma-related left tibial infection associated with extensively drug-resistant Acinetobacter baumannii and multidrug-resistant Klebsiella pneumoniae was treated with bacteriophages and antibiotics. There was rapid tissue healing and positive culture eradication. As a result, the patient's leg did not have to be amputated and he is undergoing rehabilitation.

Testosterone- and vitamin-grafted cellulose ethers for sustained release of camptothecin.

Camptothecin (CPT), a potent anticancer drug with known antiviral activity, is halted of clinical use. Few drug delivery systems of CPT are approved for therapy. Hereby, we propose the encapsulation of hydrophobic CPT in the inner core of cellulose nanoaggregates for sustained release with retaining of antiproliferative activity. Cellulose conjugates were synthesized by esterification of methyl cellulose, hydroxyethyl cellulose and (hydroxypropyl)methyl cellulose with testosterone, ergocalciferol and dl-α-tocopherol hemisuccinates. The degree of substitution attained ranged from 0.004 to 0.025 and no depolymerization was observed by size exclusion chromatography. ATR-FTIR and NMR spectroscopies confirmed grafting of testosterone and vitamins to celluloses. According to dynamic light scattering, it resulted in their self-assembly in aqueous medium as stable and slightly negatively charged nanoaggregates of 213 to 731 nm. Nanoaggregates formation was also assessed using transmission electron and atomic force microscopies. CPT was encapsulated in the cellulose nanoaggregates, achieving a content of 1.7-13.0 wt %. Sustained release of camptothecin over 150 h was observed in simulated physiological conditions. CPT-loaded cellulose nanoparticles appeared to be possible candidates for chemotherapy, according to observed cytotoxicity against MCF-7 cancer cells.

Novel Brassinosteroid-Modified Polyethylene Glycol Micelles for Controlled Release of Agrochemicals.

Two synthetic analogues of brassinosteroids (DI31 and S7) exhibit good plant growth enhancer activity. However, their hydrophobicity and quick metabolism in plants have limited their application and benefits in agriculture. Our objective was to prepare novel brassinosteroid-modified polyethylene glycol (PEG) micelles to achieve controlled release with extended stability while retaining agrochemical activity. Spectroscopic studies confirmed quantitative disubstitution of studied PEGs with the brassinosteroids, while elemental analysis assessed purity of the synthesized conjugates. Conjugates were also characterized by X-ray diffraction and thermal analysis. Dynamic and static light scattering showed stable and homogeneous approximately spherical micelles with average hydrodynamic diameters of 22-120 nm and almost neutral ζ potential. Spherical 30-140 nm micelles were observed by electron microscopy. Sustained in vitro releases at pH 5.5 were extended up to 96 h. Prepared PEG micelles showed good agrochemical activity in the radish seed bioassay and no cytotoxicity to the human microvascular endothelial cell line in the MTS test.

Chitosan Based Self-Assembled Nanoparticles in Drug Delivery.

Chitosan is a cationic polysaccharide that is usually obtained by alkaline deacetylation of chitin poly(N-acetylglucosamine). It is biocompatible, biodegradable, mucoadhesive, and non-toxic. These excellent biological properties make chitosan a good candidate for a platform in developing drug delivery systems having improved biodistribution, increased specificity and sensitivity, and reduced pharmacological toxicity. In particular, chitosan nanoparticles are found to be appropriate for non-invasive routes of drug administration: oral, nasal, pulmonary and ocular routes. These applications are facilitated by the absorption-enhancing effect of chitosan. Many procedures for obtaining chitosan nanoparticles have been proposed. Particularly, the introduction of hydrophobic moieties into chitosan molecules by grafting to generate a hydrophobic-hydrophilic balance promoting self-assembly is a current and appealing approach. The grafting agent can be a hydrophobic moiety forming micelles that can entrap lipophilic drugs or it can be the drug itself. Another suitable way to generate self-assembled chitosan nanoparticles is through the formation of polyelectrolyte complexes with polyanions. This paper reviews the main approaches for preparing chitosan nanoparticles by self-assembly through both procedures, and illustrates the state of the art of their application in drug delivery.

Traffic pollutants measured inside vehicles waiting in line at a major US-Mexico Port of Entry.

At US-Mexico border Ports of Entry, vehicles idle for long times waiting to cross northbound into the US. Long wait times at the border have mainly been studied as an economic issue, however, exposures to emissions from idling vehicles can also present an exposure risk. Here we present the first data on in-vehicle exposures to driver and passengers crossing the US-Mexico border at the San Ysidro, California Port of Entry (SYPOE). Participants were recruited who regularly commuted across the border in either direction and told to drive a scripted route between two border universities, one in the US and one in Mexico. Instruments were placed in participants' cars prior to commute to monitor-1-minute average levels of the traffic pollutants ultrafine particles (UFP), black carbon (BC) and carbon monoxide (CO) in the breathing zone of drivers and passengers. Location was determined by a GPS monitor. Results reported here are for 68 northbound participant trips. The highest median levels of in-vehicle UFP were recorded during the wait to cross at the SYPOE (median 29,692particles/cm3) significantly higher than the portion of the commute in the US (median 20,508particles/cm3) though not that portion in Mexico (median 22, 191particles/cm3). In-vehicle BC levels at the border were significantly lower than in other parts of the commute. Our results indicate that waiting in line at the SYPOE contributes a median 62.5% (range 15.5%-86.0%) of a cross-border commuter's exposure to UFP and a median 44.5% (range (10.6-79.7%) of exposure to BC inside the vehicle while traveling in the northbound direction. Reducing border wait time can significantly reduce in-vehicle exposures to toxic air pollutants such as UFP and BC, and these preventable exposures can be considered an environmental justice issue.

Development and Use of Personalized Bacteriophage-Based Therapeutic Cocktails To Treat a Patient with a Disseminated Resistant Acinetobacter baumannii Infection.

Widespread antibiotic use in clinical medicine and the livestock industry has contributed to the global spread of multidrug-resistant (MDR) bacterial pathogens, including Acinetobacter baumannii We report on a method used to produce a personalized bacteriophage-based therapeutic treatment for a 68-year-old diabetic patient with necrotizing pancreatitis complicated by an MDR A. baumannii infection. Despite multiple antibiotic courses and efforts at percutaneous drainage of a pancreatic pseudocyst, the patient deteriorated over a 4-month period. In the absence of effective antibiotics, two laboratories identified nine different bacteriophages with lytic activity for an A. baumannii isolate from the patient. Administration of these bacteriophages intravenously and percutaneously into the abscess cavities was associated with reversal of the patient's downward clinical trajectory, clearance of the A. baumannii infection, and a return to health. The outcome of this case suggests that the methods described here for the production of bacteriophage therapeutics could be applied to similar cases and that more concerted efforts to investigate the use of therapeutic bacteriophages for MDR bacterial infections are warranted.

Self-assembled hyaluronic acid nanoparticles for controlled release of agrochemicals and diosgenin.

Commercial sodium hyaluronate (HA) and synthetic hydrazide-modified HA were functionalized with diosgenin and two agrochemicals (brassinosteroids DI31 and S7) with degree of substitution ranging from 5.6 to 13.1%. The HA-steroid conjugates were studied with FTIR, 1H NMR and differential scanning calorimetry. Dynamic light scattering revealed self-assembly of the HA-steroid conjugates into stable negatively charged nanoparticles of around 159nm-441nm in water, which after drying appeared as 140nm-370nm spherically shaped nanoparticles according to transmission electron microscopy. These nanoparticles exhibited almost constant release rates of steroids for the first 8h, demonstrating sustained steroids delivery for 72h in acidic medium. The nanoparticles formed from HA-steroid conjugates were not cytotoxic to human microvascular endothelial cells (HMVEC), while the HA- brassinosteroid nanoparticles showed in vitro agrochemical activity that was superior to the activity observed for the parent brassinosteroids DI31 and S7 at 10-5 to 10-7mgmL-1.

Census of Cnidaria (Medusozoa) and Ctenophora from South American marine waters.

We have compiled available records in the literature for medusozoan cnidarians and ctenophores of South America. New records of species are also included. Each entry (i.e., identified species or still as yet not determined species referred to as "sp." in the literature) includes a synonymy list for South America, taxonomical remarks, notes on habit, and information on geographical occurrence. We have listed 800 unique determined species, in 958 morphotype entries: 5 cubozoans, 905 hydrozoans, 25 scyphozoans, 3 staurozoans, and 20 ctenophores. Concerning nomenclatural and taxonomical decisions, two authors of this census (Miranda, T.P. & Marques, A.C.) propose Podocoryna quitus as a nomen novum for the junior homonym Hydractinia reticulata (Fraser, 1938a); Euphysa monotentaculata Zamponi, 1983b as a new junior synonym of Euphysa aurata Forbes, 1848; and Plumularia spiralis Milstein, 1976 as a new junior synonym of Plumularia setacea (Linnaeus, 1758). Finally, we also reassign Plumularia oligopyxis Kirchenpauer, 1876 as Kirchenpaueria oligopyxis (Kirchenpauer, 1876) and Sertularella margaritacea Allman, 1885 as Symplectoscyphus margaritaceus (Allman, 1885).

Characterization of novel Staphylococcus aureus lytic phage and defining their combinatorial virulence using the OmniLog® system.

Skin and soft tissue infections (SSTI) caused by methicillin resistant Staphylococcus aureus (MRSA) are difficult to treat. Bacteriophage (phage) represent a potential alternate treatment for antibiotic resistant bacterial infections. In this study, 7 novel phage with broad lytic activity for S. aureus were isolated and identified. Screening of a diverse collection of 170 clinical isolates by efficiency of plating (EOP) assays shows that the novel phage are virulent and effectively prevent growth of 70-91% of MRSA and methicillin sensitive S. aureus (MSSA) isolates. Phage K, which was previously identified as having lytic activity on S. aureus was tested on the S. aureus collection and shown to prevent growth of 82% of the isolates. These novel phage group were examined by electron microscopy, the results of which indicate that the phage belong to the Myoviridae family of viruses. The novel phage group requires ß-N-acetyl glucosamine (GlcNac) moieties on cell wall teichoic acids for infection. The phage were distinct from, but closely related to, phage K as characterized by restriction endonuclease analysis. Furthermore, growth rate analysis via OmniLog® microplate assay indicates that a combination of phage K, with phage SA0420ᶲ1, SA0456ᶲ1 or SA0482ᶲ1 have a synergistic phage-mediated lytic effect on MRSA and suppress formation of phage resistance. These results indicate that a broad spectrum lytic phage mixture can suppress the emergence of resistant bacterial populations and hence have great potential for combating S. aureus wound infections.