Spontaneous bilayer wrapping of virus particles by a phospholipid Langmuir monolayer.

We report here the spontaneous formation of lipid-bilayer-wrapped virus particles, following the injection of "naked" virus particles into the subphase of a Langmuir trough with a liquid monolayer of lipids at its air-water interface. The virus particles are those of the well-studied cowpea chlorotic mottle virus, CCMV, which are negatively charged at the pH 6 of the subphase; the lipids are a 9:1 mix of neutral DMPC and cationic CTAB molecules. Before adding CCMV particles to the subphase we establish the mixed lipid monolayer in its liquid-expanded state at a fixed pressure (17.5 mN/m) and average area-per-molecule of (41Å2). Keeping the total area fixed, the surface pressure is observed to decrease at about 15 h after adding the virus particles in the subphase; by 37 h it has dropped to zero, corresponding to essentially all the lipid molecules having been removed from the air-water interface. By collecting particles from the subphase and measuring their sizes by atomic force microscopy, we show that the virus particles have been wrapped by lipid bilayers (or by two lipid bilayers). These results can be understood in terms of thermal fluctuations and electrostatic interactions driving the wrapping of the anionic virus particles by the cationic lipids. Spontaneous acquisition by a virus particle of, first, a hydrophobic lipid monolayer envelope and, then, a hydrophilic lipid bilayer envelope, as it interacts from the subphase with an oppositely charged Langmuir monolayer.

Evaluation of stress response in black-tailed prairie dogs (Cynomys ludovicianus) in arid regions from colonies in Chihuahua Mexico.

Among all the regulatory homeostatic networks in vertebrates, the activation of the hypothalamic-pituitaryadrenal axis during the stress response, has gained considerable attention, and the measurement of fecal glucocorticoids (FGC) has become an invaluable tool to assess adrenocortical activity related to stressful events in wild and captive animals. However, the use of FGC requires the validation of measurement techniques and the proper selection of the specific hormone according to the study species. The main objective of this study was to identify the dominant glucocorticoid (GC) hormone in the stress response of black-tailed prairie dogs (Cynomys ludovicianus) in an arid grassland of Chihuahua, Mexico. A capture stress challenge in the field was developed to determine if the levels of glucocorticoids (cortisol and corticosterone) both in serum and fecal samples could be attributed to stress in Cynomys ludovicianus. The samples were analysed with the technique of liquid phase radioimmunoassay , and this study showed that both cortisol and corticosterone are present at measurable levels in serum and fecal samples of black-tailed prairie dogs. We found that both GCs were present in similar concentrations in serum, however, corticosterone concentration in fecal samples was higher than cortisol. Likewise, biochemical validations performed in this study to test the assay reached acceptable levels of reliability. Therefore, we confirm that fecal analysis can be implemented as a method to measure stress responses in wild prairie dogs.

Tetrathyridia in an endemic lizard from Chile: molecular evidence for South America.

Mesocestoides is a controversial tapeworm with significant lack of data related to systematics and life cycles. This helminth has an indirect life cycle with vertebrates, mostly carnivorous mammals, as definitive hosts. Theoretically, a coprophagous arthropod would be the first intermediate host, and herptiles, mammals, and birds, which prey on these insects, would represent the second intermediate hosts. However, recent evidence suggests that this life cycle would require only two hosts, with no arthropods involved. In the Neotropics, although there are records of mammals and reptiles as hosts for Mescocestoides, no molecular analyses have been performed. This work aimed to record an additional intermediate host and molecularly characterize the isolated larvae. Thus, 18 braided tree iguanas (Liolaemus platei) from Northern Chile were collected and dissected during 2019. One lizard was parasitized by three morphotypes of larvae compatible with tetrathyridia of Mescocestoides. To achieve its specific identity, a molecular approach was performed: 18S rRNA and 12S rRNA loci were amplified through cPCR. The inferred phylogenies confirmed the morphological diagnosis and stated that all morphotypes were conspecifics. The sequences for both loci formed a monophyletic clade with high nodal support, representing a sister taxon to Mescocestoides clade C. This study represents the first molecular characterization of any taxon of Mescocestoides from the Neotropics. Future surveys from potential definitive hosts would help to elucidate its life cycle. Furthermore, an integrative taxonomic approach is required in additional studies from the Neotropical region, which would contribute to a better understanding of the evolutionary relationships of this genus.

Use of Investigator 24plex GO! To analyse allele frequencies of 21 autosomal STRs in the population of Veracruz state, Mexico.

BACKGROUND: Mexican population databases for autosomal STRs are scarce, and no previous studies have been performed with the Qiagen Investigator 24plex GO! AIM: To analyse the frequency of 21 autosomal short tandem repeat (STR) loci and forensic parameters in individuals from Veracruz state, Mexico. SUBJECTS AND METHODS: A total of 234 unrelated individuals were analysed with the Investigator 24plex GO! Kit, which includes the following autosomal STRs: TH01, D3S1358, vWA, D21S11, TPOX, D1S1656, D12S391, SE33, D10S1248, D22S1045, D19S433, D8S133879, D2S1338, D2S441, D18S51, FGA, D16S539, CSF1PO, D13S317, D5S818, and D7S820. Allele frequencies, forensic parameters, and relationships with neighbouring Mexican populations were estimated. RESULTS: The STRs analysed were in Hardy-Weinberg Equilibrium (HWE). The combined matching probability and combined PE were 1.5266 E-24 and 0.999999988711, respectively. The D18S51 and SE33 loci presented the highest Ho (0.8974 and 0.8932) and PE (0.7902 and 0.7815), respectively. The highest PIC (0.9337) and PD (0.9894) values corresponded to SE33. Conversely, D22S1045 had the lowest PIC and PE (0.5533 and 0.3546, respectively). A population cluster among southern Mexican populations, which included non-differentiation between Guerrero and Veracruz states was detected. CONCLUSION: The forensic efficacy of the 21 STRs analysed by the Investigator 24plex GO! Kit was evaluated in the Veracruz state. Moreover, new population clusters that have not yet been described and are related to geographic regions were identified, and these are in agreement with previously reported ancestral differences.

Effect of cadmium on the viability on monolayer cultures of synoviocytes, chondrocytes, and Hoffa: A preliminary study.

Osteoarthritis (OA) is the gradual loss of articular cartilage and involves several tissues, such as the synovial membrane, meniscus, ligaments, and adipose tissue known as Hoffa fat pad. There are largely unexplored factors that lead to OA development, such as the impact of exposure to heavy metals like cadmium (Cd) on the viability of cells in the knee joint tissue. The objective of this report was to identify the cell type with the highest susceptibility to Cd toxicity with respect to cell viability and death. Our findings showed that a concentration as low as 3 µM cadmium chloride for 12 h affects the viability of synovial cells, and a concentration of 10 µM affects Hoffa cells. Our results suggest that Cd can affect the viability of synovial and chondral cells primarily. In contrast, Hoffa cells were less susceptible, likely because Cd favors the production of pro-inflammatory cytokines before triggering their death as part of its damage mechanism at the articular level.

Body weight changes after adjuvant chemotherapy of patients with breast cancer: results of a Mexican cohort study.

Weight gain is observed in breast cancer patients receiving chemotherapy and is a well-known complication. Several factors that contributing to weight gain have been identified. However, there is a lack of information about factors associated with weight changes following adjuvant chemotherapy. A retrospective cohort of 200 pre- and post-menopausal Mexican patients treated for breast cancer was made. Anthropometric variables were measured before/after treatment. Biomarkers, cellular differentiation and chemotherapy were similar between groups. Weight gain occurred in 85.6% of pre-menopausal and 72.6% of post-menopausal women (p = .03). At the end of chemotherapy, weight and body mass index (BMI) did not differ significantly between pre-menopausal (69.3 ± 12.6 kg; 26.6 ± 4.8 kg/m2 ) and post-menopausal women (69.5 ± 10.9 kg; 27.3 ± 4.4 kg/m2 ) (p = .91 and 0.34). Dexamethasone doses were higher in pre-menopausal (85.7 ± 39.1 g) than post-menopausal patients (79.2 ± 22.5 g; p = .13). Weight loss was observed in 9.2% of pre-menopausal and 20.2% of post-menopausal patients (p = .04). A multivariate analysis revealed that age (OR = 2.7; 95% CI = 1.26-5.79; p = .01), menopausal status (OR = 2.29; 95% CI = 1.09-4.80; p = .03), dexamethasone dosage (OR = 2.1; 95% CI = 1.04-4.23; p = .03) and daily caloric intake (OR = 2.3; 95% CI = 1.12-5.10; p = .02) were independent variables that inducted weight gain. Pre- and post-menopausal women gained weight, but more pre-menopausal patients showed gain. An effort should be made to administer lower steroid doses to reduce weight gain.

Frequency distribution of interleukin-10 haplotypes (-1082 A>G, -819 C>T, and -592 C>A) in a Mexican population.

Interleukin 10 (IL-10) is an immunoregulatory cytokine with multiple roles in the immune system. Three single nucleotide polymorphisms at positions -1082 (A>G), -819 (C>T), and -592 (C>A) in the promoter region of the IL10 gene are believed to be associated with different inflammatory, infectious, and autoimmune diseases. These polymorphisms exhibit a strong linkage disequilibrium (LD) and form three principal haplotypes (GCC, ACC, and ATA). The GCC and ATA haplotypes have been associated with high and low levels of IL-10 production, respectively. The aim of this study was to establish the allele and haplotype frequencies of the IL10 polymorphisms in Mestizos from western Mexico. SNPs were analyzed in 340 healthy unrelated Mestizos from western Mexico by polymerase chain reaction-restriction fragment length polymorphism. The studied population presented significant differences, in the distribution of IL10 polymorphisms, from the Asian, African, and European populations. We also observed a strong LD within -1082 A>G, -819 C>T, and -592 C>A (100% pc = 7.735 x 10-18). The haplotypes ACC (45.4%), ATA (22.0%), GTA (14.9%), and GCC (13.9%) were most frequently observed in this population. The haplotype frequencies, however, differed from those reported previously in Mestizos from central Mexico, Asians, Africans, and European Caucasians, suggesting a differential gene flow in the Mexican Mestizo population. This could account for the genetic variability between Mexicans and populations of other ethnicities. The study of these polymorphisms and their haplotypes could help in expanding our knowledge to design future disease-risk studies on the western Mexican population.

First Report of Root Rot of Watermelon Caused by Ceratobasidium sp. in Sonora, Mexico.

Watermelon is one of the major crops grown in Mexico and represents 4% of the total cultivated area with fruits in this country. In 2013, Sonora State was ranked second in the production of watermelon at a national level. Fungal and oomycete diseases are among the main biotic factors affecting watermelon production, particularly those caused by species of the genera Fusarium, Phytophthora, Pythium, and Rhizoctonia. During the spring of 2013, wilting or death symptoms were confirmed in approximately 50% of ungrafted watermelon plants grown in four sampled fields along the coast of Hermosillo and Guaymas Valley in Sonora, Mexico. On both roots and stems of infected plants, localized lesions were found that were 0.2 to 2.0 cm long, reddish brown, and slightly sunken on the stem base. In some cases, the discolorations encompassed nearly 90% of the root system. One-centimeter pieces from the edge of lesions on stems and roots were superficially disinfected with 1% sodium hypochlorite, then rinsed with sterile distilled water, placed onto petri dishes containing potato dextrose agar (PDA), and incubated at 25°C for 3 days. Fungal colonies were white initially, then turned brown, and septate hyphae were 3.7 to 4.3 µm in diameter and branched at right angles with a constriction at the origin of the branch point. These characteristics are typical of the genus Rhizoctonia. Binucleate cells from five isolates were observed using a lactophenol aniline blue solution stain, according to Ceratobasidium morphological descriptions. Mycelia from five isolates grown on PDA was used for DNA extraction. The rDNA-ITS region was amplified using PCR with the universal fungal primers ITS1 and ITS4 (3). The purified products were separately sequenced in both directions using the same primer pair. The sequences obtained were 99% similar to those of Ceratobasidium sp. AG-F and AG-Fa isolates (accessions KC193238.1 on Tagetes erecta, HQ168370.1 on Musa spp., and JX913821.1 on soy-rice-weeds, respectively) from GenBank (2,4). The pathogenicity of the fungus was tested under growth chamber conditions. Sets of seven healthy watermelon seedlings of the Sugar red variety were inoculated with five isolates of Ceratobasidium. Three disks (8 mm in diameter) of mycelia grown on PDA were placed around the roots of each plantlet. The pots were maintained at 27 ± 0.1°C for 14 days with a photoperiod of 12 h. Seven uninoculated seedlings were used as a control. Initial symptoms showing water-soaked lesions developed on all inoculated seedlings within 6 to 7 days, while typical disease symptoms appeared after 10 to 14 days after inoculation. Seedlings without inoculum were free from infection. The fungus was re-isolated from the inoculated seedlings on PDA, and identified as Ceratobasidium sp., confirmed using morphological characteristics. A similar disease has been reported recently in Italy and Arizona (1); however, this report is the first description of a Ceratobasidium sp. causing root rot of watermelon in Sonora, Mexico. Agricultural areas where the study was carried represent 90% of the total area cultivated with watermelon in this state, so it is necessary to evaluate the impact of this pathogen in the crop. References: (1) C. Nischwitz et al. APS joint meeting, 2013. (2) A. Saroj et al. Plant Dis. 97:1251, 2013. (3) T. J. White et al. PCR Protocols: A Guide to Methods and Applications. Academic Press, San Diego, CA, 1990. (4) J. Yin et al. Plant Dis. 95:490, 2011.

Correlated Chained Gaussian Processes for Datasets With Multiple Annotators.

The labeling process within a supervised learning task is usually carried out by an expert, which provides the ground truth (gold standard) for each sample. However, in many real-world applications, we typically have access to annotations provided by crowds holding different and unknown expertise levels. Learning from crowds (LFC) intends to configure machine learning paradigms in the presence of multilabelers, residing on two key assumptions: the labeler's performance does not depend on the input space, and independence among the annotators is imposed. Here, we propose the correlated chained Gaussian processes from the multiple annotators (CCGPMA) approach, which models each annotator's performance as a function of the input space and exploits the correlations among experts. Experimental results associated with classification and regression tasks show that our CCGPMA performs better modeling of the labelers' behavior, indicating that it consistently outperforms other state-of-the-art LFC approaches.

Neuronal Ceroid Lipofuscinosis Type 6 (CLN6) clinical findings and molecular diagnosis: Costa Rica's experience.

BACKGROUND: Commonly known as Batten disease, the neuronal ceroid lipofuscinoses (NCLs) are a genetically heterogeneous group of rare pediatric lysosomal storage disorders characterized by the intracellular accumulation of autofluorescent material (known as lipofuscin), progressive neurodegeneration, and neurological symptoms. In 2002, a disease-causing NCL mutation in the CLN6 gene was identified (c.214G > T) in the Costa Rican population, but the frequency of this mutation among local Batten disease patients remains incompletely characterized, as do clinical and demographic attributes for this rare patient population. OBJECTIVE: To describe the main sociodemographic and clinical characteristics of patients with a clinical diagnosis for Batten Disease treated at the National Children's Hospital in Costa Rica and to characterize via molecular testing their causative mutations. METHODS: DNA extracted from buccal swabs was used for CLN6 gene sequencing. Participants' sociodemographic and clinical characteristics were also obtained from their medical records. RESULTS: Nine patients with a clinical diagnosis of Batten disease were identified. Genetic sequencing determined the presence of the previously described Costa Rican homozygous mutation in 8 of 9 cases. One patient did not have mutations in the CLN6 gene. In all cases where the Costa Rican CLN6 mutation was present, it was accompanied by a substitution in intron 2. Patients were born in 4 of the 7 Costa Rican provinces, with an average onset of symptoms close to 4 years of age. No parental consanguinity was present in pedigrees. Initial clinical manifestations varied between patients but generally included: gait disturbances, language problems, visual impairment, seizures and psychomotor regression. Cortical and cerebellar atrophy was a constant finding when neuroimaging was performed. Seizure medication was a common element of treatment regimens. CONCLUSIONS: This investigation supports that the previously characterized c.214G > T mutation is the most common causative NCL mutation in the Costa Rican population. This mutation is geographically widespread among Costa Rican NCL patients and yields a clinical presentation similar to that observed for CLN6 NCL patients in other geographies.

Impact of Cadmium Mediated by Tobacco Use in Musculoskeletal Diseases.

Tobacco use has a negative impact on health due to its relationship with the development of high-mortality diseases, such as pulmonary cancer. However, the effect of cadmium (Cd), present in tobacco smoke, on the development of joint diseases has been scarcely studied. The objective of this review is to discuss the evidence regarding the mechanisms by which Cd exposure, through tobacco smoke, may lead to the development of osteoarthritis (OA), osteoporosis (OP), and rheumatoid arthritis (RA). There's evidence suggesting a string association between moderate to severe OA development and tobacco use, and that a higher blood concentration of Cd can trigger oxidative stress (OS) and inflammation, favoring cartilage loss. At the bone level, the Cd that is inhaled through tobacco smoke affects bone mineral density, resulting in OP mediated by a decrease in the antioxidant enzymes, which favors the bone resorption process. In RA, tobacco use promotes the citrullination process through Cd exposure and increases OS and inflammation. Understanding how tobacco use can increase the damage at the articular level mediated by a toxic metal, i.e., Cd, is important. Finally, we propose prevention, control, and treatment strategies for frequently disabling diseases, such as OA, OP, and RA to reduce its prevalence in the population.

Controlling the surface charge of simple viruses.

The vast majority of plant viruses are unenveloped, i.e., they lack a lipid bilayer that is characteristic of most animal viruses. The interactions between plant viruses, and between viruses and surfaces, properties that are essential for understanding their infectivity and to their use as bionanomaterials, are largely controlled by their surface charge, which depends on pH and ionic strength. They may also depend on the charge of their contents, i.e., of their genes or-in the instance of virus-like particles-encapsidated cargo such as nucleic acid molecules, nanoparticles or drugs. In the case of enveloped viruses, the surface charge of the capsid is equally important for controlling its interaction with the lipid bilayer that it acquires and loses upon leaving and entering host cells. We have previously investigated the charge on the unenveloped plant virus Cowpea Chlorotic Mottle Virus (CCMV) by measurements of its electrophoretic mobility. Here we examine the electrophoretic properties of a structurally and genetically closely related bromovirus, Brome Mosaic Virus (BMV), of its capsid protein, and of its empty viral shells, as functions of pH and ionic strength, and compare them with those of CCMV. From measurements of both solution and gel electrophoretic mobilities (EMs) we find that the isoelectric point (pI) of BMV (5.2) is significantly higher than that of CCMV (3.7), that virion EMs are essentially the same as those of the corresponding empty capsids, and that the same is true for the pIs of the virions and of their cleaved protein subunits. We discuss these results in terms of current theories of charged colloidal particles and relate them to biological processes and the role of surface charge in the design of new classes of drug and gene delivery systems.

[Neurological complications associated with extracorporeal membrane oxygenation (ECMO) therapy in adult patients. A study of a case series]. / Complicaciones neurológicas asociadas al tratamiento con oxigenación por membrana extracorpórea (ECMO) en pacientes adultos. Estudio de una serie de casos.

INTRODUCTION: ECMO is an advanced technique of ventilatory and circulatory support. However, it can be associated with neurological complications. The proposal is to describe the clinical characteristics and neurological complications profile in patients under ECMO support. PATIENTS AND METHODS: To descriptive a case series study. A descriptive and retrospective analysis and a bivariate analysis were performed in order to compare the main clinical variables of interest. RESULTS: 136 adults undergoing ECMO with an average age of 51 years (17-78) were evaluated. Neurological complications were observed in 51 patients (37.5%), corresponding to stroke 22 (16.17%), hypoxic encephalopathy 13 (9.5 %), cerebral hemorrhage (HIC) in 12 (8.8%) and subarachnoid hemorrhage (HSA) in 4 patients (2.9%). Seven (13.7%) of patients with neurological complications had seizures. Neurological complications occurred in 23.53% in venovenous ECMO and in 76.47% with veno-arterial ECMO (p = 0.86). The overall mortality was 51.47% (70/136) for all patients in ECMO and 64.7% (33/51) for the population with neurological complications. The mortality in stroke was 54.5% (12/22), 91.6% (11/12) in HIC and 100% (4) in HSA (p = 0.03). Mortality was higher in veno-arterial ECMO (77.14%) versus venous-venous ECMO (22.86% of total), (p = 0.015). CONCLUSIONS: ECMO is a useful therapeutic tool in cases of high clinical severity. In our study, we identified a high rate of neurological complications that contribute to associated morbidity and mortality. Early neuroimaging studies in these cases could allow early detection of these complications.

TITLE: Complicaciones neurológicas asociadas al tratamiento con oxigenación por membrana extracorpórea (ECMO) en pacientes adultos. Estudio de una serie de casos.Introducción. La ECMO es una técnica avanzada de soporte ventilatorio y circulatorio. Sin embargo, puede asociarse a complicaciones neurológicas. Se propone describir las características clínicas y el perfil de las complicaciones neurológicas en pacientes sometidos a ECMO. Pacientes y métodos. Estudio descriptivo retrospectivo de una serie de casos. Se realizó un análisis descriptivo y un análisis bivariado con la finalidad de comparar las principales variables clínicas de interés. Resultados. Se evaluó a 136 adultos sometidos a ECMO con edad promedio de 51 años (17-78). Las complicaciones neurológicas se presentaron en 51 pacientes (37,5%), de los cuales correspondieron a ictus 22 (16,17%); a encefalopatía hipóxica, 13 (9,5%); a hemorragia intracerebral (HIC), 12 (8,8%), y a hemorragia subaracnoidea (HSA), cuatro (2,9%). Siete (13,7%) de los pacientes con complicaciones neurológicas presentaron crisis epilépticas. Las complicaciones neurológicas se presentaron en 12 pacientes (23,53%) con la ECMO venovenosa y en 39 (76,47%) con la ECMO venoarterial (p = 0,86). La mortalidad global fue del 51,47% (70/136 pacientes) y del 64,7% (33/51) para la población con complicaciones neurológicas. La mortalidad en el ictus fue del 54,5% (12/22), del 91,6% (11/12) en la HIC y del 100% (4/4) en la HSA (p = 0,03). La mortalidad en la ECMO venoarterial fue del 77,14%, frente al 22,86% de la de la ECMO venovenosa (p = 0,015). Conclusiones. La ECMO es una herramienta terapéutica útil en casos de elevada gravedad clínica. En nuestro estudio, identificamos una elevada tasa de complicaciones neurológicas que contribuyen a la morbimortalidad asociada. La realización temprana de estudios de neuroimagen en estos casos podría permitir una detección temprana de estas complicaciones.

Tissue engineering of cartilage using poly-epsilon-caprolactone nanofiber scaffolds seeded in vivo with periosteal cells.

OBJECTIVE: To determine the potential of periosteal cells to infiltrate poly-epsilon-caprolactone (PCL) nanofiber scaffolds in vivo and subsequently produce cartilage in vitro. DESIGN: PCL nanofiber scaffolds, with or without chitosan-coating were implanted under periosteum in 6-month-old rabbits. Transforming growth factor-beta1 (TGF-beta1) or vehicle was injected into each implant site. After 1, 3, 5 or 7 days, scaffolds were removed, separated from the periosteum, and the scaffolds and periosteum were cultured separately for 6 weeks under chondrogenic conditions. Sulfated glycosaminoglycan (GAG), type II collagen, DNA content, cartilage yield, and calcium deposition were then analyzed. RESULTS: Cell infiltration was observed in all scaffolds. Cartilage formation in the uncoated scaffolds increased with duration of implantation (maximum at 7 days). Cells in the uncoated scaffolds implanted for 7 days produced significantly higher levels of both GAG [560 (95% confidence interval (CI), 107-1013) vs 228 (95% CI, 177-278) microg GAG/microg DNA] and cartilage yield [9% (95% CI, 3-14%) vs 0.02% (95% CI, 0-0.22%)] compared to chitosan-coated scaffolds (P=0.006 or less). There was no significant difference in GAG content or cartilage yield between the TGF-beta1-injected and vehicle-injected scaffolds. However, significantly more mineral deposition was detected in TGF-beta1-injected scaffolds compared to vehicle-injected scaffolds (P<0.0001). Cartilage yield from the periosteum, moreover, was significantly increased by subperiosteal TGF-beta1 injections (P<0.001). However, this response was reduced when chitosan-coated scaffolds were implanted. CONCLUSIONS: This study demonstrates that it is possible to seed PCL nanofiber scaffolds with periosteal cells in vivo and subsequently produce engineered cartilage in vitro.

Pretreatment of periosteum with TGF-beta1 in situ enhances the quality of osteochondral tissue regenerated from transplanted periosteal grafts in adult rabbits.

OBJECTIVE: To compare the efficacy of in situ transforming growth factor-beta1 (TGF-beta1)-pretreated periosteum to untreated periosteum for regeneration of osteochondral tissue in rabbits. METHODS: In the pretreatment group, 12 month-old New Zealand white rabbits received subperiosteal injections of 200 ng of TGF-beta1 percutaneously in the medial side of the proximal tibia, 7 days prior to surgery. Control rabbits received no treatment prior surgery. Osteochondral transverse defects measuring 5mm proximal to distal and spanning the entire width of the patellar groove were created and repaired with untreated or TGF-beta1-pretreated periosteal grafts. Post-operatively the rabbits resumed normal cage activity for 6 weeks. RESULTS: Complete filling of the defects with regenerated tissue was observed in both the TGF-beta1-pretreated and control groups with reformation of the original contours of the patellar groove. The total histological score (modified O'Driscoll) in the TGF-beta1-pretreated group, 20 (95% Confidence Interval (CI), 19-21), was significantly higher (P=0.0001) than the control group, 18 (16-19). The most notable improvements were in structural integrity and subchondral bone regeneration. No significant differences in glycosaminoglycan or type II collagen content, or equilibrium modulus were found between the surgical groups. The cambium of the periosteum regenerated at the graft harvest site was significantly thicker (P=0.0065) in the TGF-beta1-pretreated rabbits, 121 microm (94-149), compared to controls, 74 microm (52-96), after 6 weeks. CONCLUSIONS: This study demonstrates that in situ pretreatment of periosteum with TGF-beta1 improves osteochondral tissue regeneration at 6-weeks post-op compared to untreated periosteum in 12 month-old rabbits.

CNN-based framework using spatial dropping for enhanced interpretation of neural activity in motor imagery classification.

Interpretation of brain activity responses using motor imagery (MI) paradigms is vital for medical diagnosis and monitoring. Assessed by machine learning techniques, identification of imagined actions is hindered by substantial intra- and inter-subject variability. Here, we develop an architecture of Convolutional Neural Networks (CNN) with an enhanced interpretation of the spatial brain neural patterns that mainly contribute to the classification of MI tasks. Two methods of 2D-feature extraction from EEG data are contrasted: Power Spectral Density and Continuous Wavelet Transform. For preserving the spatial interpretation of extracting EEG patterns, we project the multi-channel data using a topographic interpolation. Besides, we include a spatial dropping algorithm to remove the learned weights that reflect the localities not engaged with the elicited brain response. We evaluate two labeled scenarios of MI tasks: bi-class and three-class. Obtained results in an MI database show that the thresholding strategy combined with Continuous Wavelet Transform improves the accuracy and enhances the interpretability of CNN architecture, showing that the highest contribution clusters over the sensorimotor cortex with a differentiated behavior of rhythms [Formula: see text] and [Formula: see text].

Effect of cadmium on the concentration of essential metals in a human chondrocyte micromass culture.

BACKGROUND: An essential element imbalance in the joint might favor gradual degeneration of the articular cartilage. It has been reported that cadmium (Cd) plays an antagonistic role with regards to the presence of essential elements, such as zinc (Zn), iron (Fe), and manganese (Mn), which may favor the development of disabling diseases, like osteoarthritis (OA) and osteoporosis. METHODS: 3D cultures of human chondrocytes were phenotyped with the Western blot technique and structurally evaluated with histological staining. The samples were exposed to 1, 5, and 10 µM of CdCl2 for 12 h, with a non-exposed culture as control. The concentration of Cd, Fe, Mn, Zn, chromium (Cr), and nickel (Ni) was quantified through plasma mass spectrometry (ICP-MS). The data were analyzed with a Kruskal Wallis test, a Kendall's Tau test and Spearman's correlation coefficient with the Stata program, version 14. RESULTS: Our results suggest that Cd exposure affects the structure of micromass cultures and plays an antagonistic role on the concentration of essential metals, such as Zn, Ni, Fe, Mn, and Cr. CONCLUSION: Cd exposure may be a risk factor for developing joint diseases like OA, as it can interfere with cartilage absorption of other essential elements that maintain cartilage homeostasis.

Mycobacterium tuberculosis CysA2 is a dual sulfurtransferase with activity against thiosulfate and 3-mercaptopyruvate and interacts with mammalian cells.

Cyanide is a toxic compound that is converted to the non-toxic thiocyanate by a rhodanese enzyme. Rhodaneses belong to the family of transferases (sulfurtransferases), which are largely studied. The sulfur donor defines the subfamily of these enzymes as thiosulfate:cyanide sulfurtransferases or rhodaneses (TSTs) or 3-mercaptopyruvate sulfurtransfeases (MSTs). In Mycobacterium tuberculosis, the causative agent of tuberculosis, the gene Rv0815c encodes the protein CysA2, a putative uncharacterized thiosulfate:cyanide sulfurtransferase that belongs to the essential sulfur assimilation pathway in the bacillus and is secreted during infection. In this work, we characterized the functional and structural properties of CysA2 and its kinetic parameters. The recombinant CysA2 is a α/ß protein with two rhodanese-like domains that maintains the functional motifs and a catalytic cysteine. Sulfurtransferase activity was determined using thiosulfate and 3-mercaptopyruvate as sulfur donors. The assays showed Km values of 2.89 mM and 7.02 mM for thiosulfate and 3-mercaptopyruvate, respectively, indicating the protein has dual activity as TST and MST. Immunological assays revealed that CysA2 interacted with pulmonary cells, and it was capable to activate macrophages and dendritic cells, indicating the stimulation of the immune response, which is important for its use as an antigen for vaccine development and immunodiagnostic.

Toxicity of cadmium in musculoskeletal diseases.

Epidemiological studies have reported that exposure to toxic metals like cadmium (Cd) may promote the development of musculoskeletal diseases, such as osteoporosis, rheumatoid arthritis (RA), and osteoarthritis (OA), among others. The objective of this review is to summarize the molecular mechanisms of inflammation and oxidative stress activated by Cd at the bone level, particularly in osteoporosis, RA, and OA. Cadmium can increase bone resorption, affect the activity of osteoclasts and calcium (Ca) absorption, and impair kidney function, which favors the development of osteoporosis. In the case of RA, Cd interferes with the activity of antioxidant proteins, like superoxide dismutase (SOD) and catalase (CAT). It also promotes an inflammatory state, inducing the process of citrullination, which affects the proteins of immune response. On the other hand, accumulation of Cd in the tissues and blood of smokers has been related to the development of some musculoskeletal diseases. Therefore, knowing the negative impact of Cd toxicity at the articular level can help understand the damage mechanisms it produces, leading to the development of such diseases.

[Comparison of the functional outcomes of patients with arthroscopic repair of massive rotator cuff ruptures alone or combined with acromioplasty or biceps tenotomy]. / Comparación de los resultados funcionales de los pacientes con reparación artroscópica de rupturas masivas del manguito rotador sola o combinada con acromioplastía y/o tenotomía del bíceps.

BACKGROUND: The rotator cuff injury it is one of the most common causes of pain and functional disability of the shoulder with an annual reported incidence of 4.5 million cases in the United States. It is one of the leading causes of pain of shoulder in patients older than 60 years. In Mexico, there are no reports of the incidence or the results of arthroscopic repair of massive rotator cuff lesions alone or combined with other procedures. OBJECTIVE: To evaluate the clinical evolution of patients post-surgery of arthroscopic rotator cuff massive injury repair AR-RCMI alone or in combination with other techniques. METHODS: Evaluation of records of patients with AR-RCMI post-surgery, comparing the results of the scales: simple shoulder test and VAS before and after surgery with a follow up of 2.6 years. The combined procedures were acromioplasty, tenotomy of biceps or both. RESULTS: 65 patients with diagnosis of massive injury; with an average age of 62.8 years (SD ± 9. 42), 27.7% were men and 72.3% women. The evaluation was conducted in four groups: arthroscopic repair (AR); arthroscopic repair + biceps tenotomy (AR + BT); arthroscopic repair + acromioplasty (AR + A) and arthroscopic repair + biceps tenotomy + acromioplasty (AR + BTA). All groups showed significant reduction in pain: AR (-44.1%, p = 0.0001), AR + A (-36.9%, p = 0.001), AR + BT (-36.3%, p = 0.0001), AR + BT + A (-38.5%, p = 0.0001). All groups had significant improvement in function with the SST scale.

ANTECEDENTES: La lesión del manguito rotador (LMR) es una de las causas más comunes de dolor y discapacidad funcional del hombro con una incidencia anual reportada de 4.5 millones de casos en Estados Unidos. La LMR es una de las principales causas de dolor de hombro en pacientes mayores de 60 años. En México, no existen reportes de la incidencia ni de los resultados de la reparación artroscópica de las lesiones masivas de manguito rotador sola o combinada con otros procedimientos. OBJETIVO: Evaluar la evolución clínica de los pacientes postoperados de reparación artroscópica de lesión masiva del manguito rotador (RA-LMMR), sola o combinada con otras técnicas. MÉTODOS: Evaluación de expedientes de pacientes postoperados de RA-LMMR en la que se compararon los resultados de las escalas: simple shoulder test y EVA antes y después de la cirugía a un seguimiento promedio de 2.6 años. Los procedimientos combinados fueron acromioplastía, tenotomía de bíceps o ambas. RESULTADOS: 65 pacientes con diagnóstico de lesión masiva con edad promedio de 62.8 años (DE ± 9.42), 27.7% fueron hombres y 72.3% mujeres. La evaluación se realizó en cuatro grupos: reparación artroscópica (RA), reparación artroscópica + tenotomía del bíceps (RA + TB), reparación artroscópica + acromioplastía (RA + A) y reparación artroscópica + tenotomía del bíceps + acromioplastía (RA + TBA). Todos los grupos mostraron disminución significativa del dolor: RA (-44.1%, p = 0.0001), RA + A (-36.9%, p = 0.001), RA + TB (-36.3%, p = 0.0001), RA + TB + A (-38.5%, p = 0.0001). De igual forma todos los grupos mostraron mejoría significativa de la función evaluada con la escala SST.