Genetics of white color and iridophoroma in "Lemon Frost" leopard geckos.

The squamates (lizards and snakes) are close relatives of birds and mammals, with more than 10,000 described species that display extensive variation in a number of important biological traits, including coloration, venom production, and regeneration. Due to a lack of genomic tools, few genetic studies in squamates have been carried out. The leopard gecko, Eublepharis macularius, is a popular companion animal, and displays a variety of coloration patterns. We took advantage of a large breeding colony and used linkage analysis, synteny, and homozygosity mapping to investigate a spontaneous semi-dominant mutation, "Lemon Frost", that produces white coloration and causes skin tumors (iridophoroma). We localized the mutation to a single locus which contains a strong candidate gene, SPINT1, a tumor suppressor implicated in human skin cutaneous melanoma (SKCM) and over-proliferation of epithelial cells in mice and zebrafish. Our work establishes the leopard gecko as a tractable genetic system and suggests that a tumor suppressor in melanocytes in humans can also suppress tumor development in iridophores in lizards.

Effects of Motor Control Exercises in Patients With Chronic Nonspecific Low Back Pain: A Systematic Review and Meta-Analysis.

OBJECTIVE: The primary objective of this systematic review is to assess whether motor control exercises consisting of the methodology described by Richardson and Hodges improve the pain and disability of patients with nonspecific low back pain. DESIGN: Systematic review and a meta-analysis. SETTING: A literature review was conducted using PubMed, PEDro, Scielo, CINAHL, Web of Science, Dialnet, Scopus, and MEDLINE from inception to November 2021. PATIENTS: Patients with chronic nonspecific low back pain. INTERVENTIONS: Randomized controlled trials assessing motor control exercises versus inactive control, placebo or minimal intervention, and other exercises. MAIN OUTCOME MEASURES: Pain intensity, disability, and physical activity were considered as primary outcomes. RESULTS: Eighteen studies with 1356 patients were finally included in the systematic review, of which only 13 randomized clinical trials could be meta-analyzed. Statistically significant results were found in favor of the motor control group for the comparison with other exercises in disability at postintervention term (Mean Difference, 95% Confidence Interval [CI], -3.13 [-5.87 to -0.38], P = 0.03); for the comparison with inactive control, placebo, or minimal intervention in pain at postintervention term (MD, 95% CI, -18.10 [-30.79 to -5.41], P = 0.008); and for comparison with general exercises (MD, 95% CI, -12.70 [-20.80 to -4.60], P = 0.002). CONCLUSIONS: Moderate-quality evidence regarding the effectiveness of motor control exercises to reduce pain intensity and disability exists, but the reduction should be interpreted with caution.

Efficacy of e-Health Interventions in Patients with Chronic Low-Back Pain: A Systematic Review with Meta-Analysis.

Introduction: Low-back pain (LBP) is the leading cause of disability worldwide. Around 75-84% of the world's population will experience LBP at some point, establishing it as a major global health problem. e-Health is the remote delivery of therapeutic services, clinical information, and medical care, and may prove a very useful approach to tackle this pathology. Objectives: To evaluate the efficacy of e-health-based interventions in improving the symptoms of chronic LBP. Methods: A systematic review with meta-analysis was performed in PubMed, Web of Science, and PEDro until January 2022 through the assessment of methodological quality of systematic reviews (AMSTAR). Studies were included in which e-health interventions were used as experimental treatment compared to physical therapy to determine changes in back-specific functional status and pain in patients with chronic LBP. Two reviewers examined the sources individually, calculated the risk of bias, and extracted the data (PROSPERO number CRD42022306130). The effect size was calculated using the standardized mean difference (SMD) and its confidence interval (95% CI). Results: A total of 9 randomized controlled trials with 3,180 participants were included. The results of the findings showed an effect of e-health compared to other physical therapy on short-term (SMD = -0.59, 95% CI: -1.77 to 0.59) and intermediate short-term (SMD = -0.40, 95% CI: -0.91 to 0.11) pain intensity and back-specific functional status in the short term (SMD = -0.20, 95% CI: -0.81 to 0.41) and intermediate short term (SMD = -0.30, 95% CI: -0.74 to 0.14). The effect of e-health compared to minimal intervention on short-term intermediate pain intensity (SMD = -0.64, 95% CI: -1.72 to 0.45) and short-term intermediate back-specific functional status (SMD = -0.39, 95% CI: -0.87 to 0.09). Conclusions: e-Health interventions based on self-maintenance and education are as effective on pain and back-specific functional status as other face-to-face or home-based interventions in patients with chronic LBP, with moderate scientific evidence.

A viable allele of Mcm4 causes chromosome instability and mammary adenocarcinomas in mice.

Mcm4 (minichromosome maintenance-deficient 4 homolog) encodes a subunit of the MCM2-7 complex (also known as MCM2-MCM7), the replication licensing factor and presumptive replicative helicase. Here, we report that the mouse chromosome instability mutation Chaos3 (chromosome aberrations occurring spontaneously 3), isolated in a forward genetic screen, is a viable allele of Mcm4. Mcm4(Chaos3) encodes a change in an evolutionarily invariant amino acid (F345I), producing an apparently destabilized MCM4. Saccharomyces cerevisiae strains that we engineered to contain a corresponding allele (resulting in an F391I change) showed a classical minichromosome loss phenotype. Whereas homozygosity for a disrupted Mcm4 allele (Mcm4(-)) caused preimplantation lethality, Mcm(Chaos3/-) embryos died late in gestation, indicating that Mcm4(Chaos3) is hypomorphic. Mutant embryonic fibroblasts were highly susceptible to chromosome breaks induced by the DNA replication inhibitor aphidicolin. Most notably, >80% of Mcm4(Chaos3/Chaos3) females succumbed to mammary adenocarcinomas with a mean latency of 12 months. These findings suggest that hypomorphic alleles of the genes encoding the subunits of the MCM2-7 complex may increase breast cancer risk.

Anti-HIV small-molecule binding in the peptide subpocket of the CXCR4:CVX15 crystal structure.

The CXC chemokine receptor 4 (CXCR4) is involved in chemotaxis and serves as a coreceptor for T-tropic HIV-1 viral entry, thus making this receptor an attractive drug target. Recently, crystal structures of CXCR4 were reported as complexes with the small molecule IT1t and the CVX15 peptide. Follow-up efforts to model different antagonists into the small molecule CXCR4:IT1t crystal structure did not generate poses consistent with either the X-ray crystal structure or site-directed mutagenesis (SDM). Here, we compare the binding pockets of the two CXCR4 crystal structures, revealing differences in helices IV, V, VI, and VII, with major differences for the His203 residue buried in the binding pocket. The small molecule antagonist AMD11070 was docked into both CXCR4 crystal structures. An AMD11070 pose identified from the CXCR4:CVX15 model presented interactions with Asp171, Glu288, Trp94, and Asp97, consistent with published SDM data, thus suggesting it is the bioactive pose. A CXCR4 receptor model was optimized around this pose of AMD11070, and the resulting model correlated HIV-1 inhibition with MM-GBSA docking scores for a congeneric AMD11070-like series. Subsequent NAMFIS NMR results successfully linked the proposed binding pose to an independent experimental structure. These results strongly suggest that not all small molecules will bind to CXCR4 in a similar manner as IT1t. Instead, the CXCR4:CVX15 crystal structure may provide a binding locus for small organic molecules that is more suitable than the secondary IT1t site. This work is expected to provide modeling insights useful for future CXCR4 antagonist and X4-tropic HIV-1 based drug design efforts.

Effects of monopolar pulsed-capacitive dielectric radiofrequency diathermy in patients with chronic low back pain: a randomised clinical trial.

Monopolar capacitive diathermy is a physiotherapy technique that uses high-frequency currents to generate heat in deep tissues. This heat can have several therapeutic effects, especially in the treatment of chronic low back pain (CLBP), however, until now there is little evidence of this type of diathermy. The purpose was to evaluate the efficacy of a pulsed monopolar dielectric radiofrequency diathermy (PRF)-capacitive type versus simulated treatment on symptomatology of patients with CLBP. A single-blind randomised controlled trial was conducted. Sixty patients with CLBP were randomly assigned to a PRF-capacitive or a simulated treatment group. All participants received 3 sessions per week for 3 weeks. Disability, pain intensity, movement phobia, lumbar anteflexion, quality of life, and sleep quality were assessed at baseline, after treatment, and at two months. The application of 9 sessions of PRF-capacitive showed significant improvements compared to simulated therapy during the entire follow-up for disability (F = 26.99, p < 0.001), pain intensity (F = 0.550, p < 0.001), the quality of life components of physical function (F = 0.780, p < 0.001), social function (F = 0.780, p < 0.001) and mental health (F = 0.858, p = 0.003) and for sleep duration (F = 0.863, p = 0.004).

Cellular Internalization and Toxicity of Chitosan Nanoparticles Loaded with Nobiletin in Eukaryotic Cell Models (Saccharomyces cerevisiae and Candida albicans).

This study involved the synthesis and characterization of chitosan nanoparticles loaded with nobiletin (CNpN) and assessed their toxicity and cellular internalization in eukaryotic cell models (Saccharomyces cerevisiae and Candida albicans). Nanoparticles were prepared via the nanoprecipitation method and physicochemically characterized to determine their hydrodynamic diameter using dynamic light scattering (DLS), their surface charge through ζ-potential measurements, and their chemical structure via Fourier-transform infrared spectroscopy (FTIR). The hydrodynamic diameter and ζ-potential of chitosan nanoparticles (CNp) and CNpN were found to be 288.74 ± 2.37 nm and 596.60 ± 35.49 nm, and 34.51 ± 0.66 mV and 37.73 ± 0.19 mV, respectively. The scanning electron microscopy (SEM) images displayed a particle size of approximately 346 ± 69 nm, with notable sphericity for CNpN. FTIR analysis provided evidence of potential imine bonding between chitosan and nobiletin. Membrane integrity damage could be observed in both S. cerevisiae and C. albicans yeast stained with propidium iodide, demonstrating membrane integrity damage caused by CNp and CNpN, where higher concentration treatments inhibited the development of yeast cells. These findings suggest a selective therapeutic potential of CNpN, which could be promising for the development of antifungal and anticancer therapies. This study contributes to understanding the interaction between nanoparticles and eukaryotic cells, offering insights for future biomedical applications.

Transmitted Drug Resistance and HIV Diversity Among Adolescents Newly Diagnosed With HIV in Spain.

BACKGROUND: Virologic characterization of newly HIV-diagnosed adolescents could help to improve their specific needs. The objective was to describe the transmitted drug resistance mutations (TDR) and its transmission by clusters in this population in Spain. METHODS: TDR to retrotranscriptase and protease inhibitors included in the WHO TDR list 2009 implemented in the Calibrated Population Resistance tool v8.0 (Stanford) were studied in HIV pol sequences from all HIV-diagnosed adolescents (12-19-year-old) enrolled during 2004-2019 period in the Spanish pediatric and adult (CoRISpe-CoRIS) cohorts. The found TDR were compared with the provided by the Stanford algorithm v9.0 2021. HIV-1 variants and transmission clusters were also studied. RESULTS: Among 410 HIV-1 adolescents diagnosed, 141 (34.4%) had available ART-naive sequences. They were mostly male (81.6%), Spanish (55.3%) and with behavioral risk (92.2%), mainly male-to-male sexual contact (63.1%). TDR prevalence was significantly higher by Stanford versus WHO list (18.4% vs. 7.1%; P = 0.004). The most prevalent TDR by the WHO list was K103N (3.6%) and by Stanford E138A (6.6%), both at retrotranscriptase. E138A, related to rilpivirine/etravirine resistance, was absent in the WHO list. One in 4 adolescents carried HIV-1 non-B variants. We described 5 transmission clusters, and 2 carried TDR mutations. CONCLUSIONS: Our data suggest a high TDR prevalence in adolescents with a new HIV diagnosis in Spain, similar to adults, 2 active TDR transmission clusters, and the need for the WHO TDR list update. These findings could have implications for the options of the recently available rilpivirine-related long-acting treatment and in first-line regimen election.

Factors related with symptom duration until diagnosis and treatment of symptomatic colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) survival depends mostly on stage at the time of diagnosis. However, symptom duration at diagnosis or treatment have also been considered as predictors of stage and survival. This study was designed to: 1) establish the distinct time-symptom duration intervals; 2) identify factors associated with symptom duration until diagnosis and treatment. METHODS: This is a cross-sectional study of all incident cases of symptomatic CRC during 2006-2009 (795 incident cases) in 5 Spanish regions. Data were obtained from patients' interviews and reviews of primary care and hospital clinical records. MEASUREMENTS: CRC symptoms, symptom perception, trust in the general practitioner (GP), primary care and hospital examinations/visits before diagnosis, type of referral and tumor characteristics at diagnosis. Symptom Diagnosis Interval (SDI) was calculated as time from first CRC symptoms to date of diagnosis. Symptom Treatment Interval (STI) was defined as time from first CRC symptoms until start of treatment. Nonparametric tests were used to compare SDI and STI according to different variables. RESULTS: Symptom to diagnosis interval for CRC was 128 days and symptom treatment interval was 155. No statistically significant differences were observed between colon and rectum cancers. Women experienced longer intervals than men. Symptom presentation such as vomiting or abdominal pain and the presence of obstruction led to shorter diagnostic or treatment intervals. Time elapsed was also shorter in those patients that perceived their first symptom/s as serious, disclosed it to their acquaintances, contacted emergencies services or had trust in their GPs. Primary care and hospital doctor examinations and investigations appeared to be related to time elapsed to diagnosis or treatment. CONCLUSIONS: Results show that gender, symptom perception and help-seeking behaviour are the main patient factors related to interval duration. Health service performance also has a very important role in symptom to diagnosis and treatment interval. If time to diagnosis is to be reduced, interventions and guidelines must be developed to ensure appropriate examination and diagnosis during both primary and hospital care.

The Efficacy of Strength Exercises for Reducing the Symptoms of Menopause: A Systematic Review.

BACKGROUND: The aim of this systematic review was to determine whether strength exercises improve the symptoms of menopause and to provide an update on the most recent scientific evidence on the type and regimen of exercise that help reduce the symptoms. METHODS: An electronic search of scientific databases was performed from 2015 to 2022. Randomized clinical trials that analyzed the effects of strength exercises versus other types of interventions, considering all the outcome measures of interest, were included in this review. RESULTS: We found 5964 potential articles. After applying the selection criteria, we selected 12 of the articles. The studies compared strength exercises versus other therapies or compared strength exercises versus no intervention in one of the groups. The results showed improvements in the strength of the legs and pelvic floor, physical activity, bone density, metabolic and hormonal changes, heart rate and blood pressure and a change in hot flashes. CONCLUSIONS: There is evidence that strength exercises can be beneficial for improving strength, physical activity, bone density and hormonal and metabolic levels. In terms of the appropriate type of strength training, the evidence is still unclear given that the same benefits are achieved by various types of exercises.

Factors related to bladder catheterization in older patients and its possible association with prognosis: results of the EDEN-30 study. / Factores relacionados con la práctica de sondaje vesical en urgencias en pacientes ancianos y su relación con el pronóstico: resultados del estudio EDEN-30.

OBJECTIVES: The aims of this study in the Emergency Department and Elder Needs (EDEN) series were to explore associations between clinical variables on arrival at the ED (baseline) and the insertion of a bladder catheter, and the relation between catheterization and deterioration to a more complex or serious clinical state. MATERIAL AND METHODS: Included were all patients aged 65 years or older attended during 1 week in 52 Spanish EDs. Patients were grouped according to whether a bladder catheter was or was not inserted in the ED. We used multivariable logistical regression to explore associations between catheterization and patient age, sex, 10 comorbidities, 7 baseline status variables, and 6 clinical variables. Progression was considered serious or complex if the patient died or required hospitalization, a prolonged hospital stay, or discharge to a care facility. We also explored the association between age and catheterization using adjusted restricted cubic spline (RCS) curves with a cutoff value of 65 years. RESULTS: Participating hospitals enrolled 24 573 patients; bladder catheters were inserted in 976 (4%). Of these, 44.3% were discharged from the ED. Fifteen of the 24 variables were independently associated with bladder catheterization. Factors with the strongest associations according to odds ratios (ORs) were impaired consciousness (OR, 2.50; 95% CI, 1.90-3.30), dehydration (OR, 2.24; 95% CI, 1.85-2.72), and male sex (OR, 2.12; 95% CI, 1.84- 2.44). Age 80 years or older was also associated with bladder catheterization (OR, 1.17; 95% CI, 1.01-1.358). The adjusted RCS curves showed a progressive linear increase in the probability of catheterization with age. The increase was constant in men and stabilized after the age of 85 years in women (P-interaction .001). Bladder catheterization was associated with hospitalization (OR, 2.31; 95% CI, 1.99-2.68), intensive care unit admission (OR, 4.64; 95% CI, 3.04-7.09), prolonged stay in the ED for discharged patients (OR, 2.28; 95% CI, 1.75-2.96), in-hospital death (OR, 1.99; 95% CI, 1.54-2.57), and 30-day death (OR, 1.66; 95% CI, 1.33-2.08). No associations were found between catheterization and prolonged hospital stay (OR, 1.11; 95% CI, 0.92-1.34) or need for a care facility on discharge (OR, 1.50; 95% CI, 0.98-2.29). CONCLUSION: Certain patient characteristics and baseline clinical conditions are associated with bladder catheterization in patients of advanced age. The main factors were decreased consciousness, dehydration, and male sex. Even after adjustment for related factors, catheterization is independently associated with progression to more complex or serious clinical states.

OBJETIVO: Estudiar las variables de estado basal y de situación clínica a la llegada a urgencias relacionadas con la práctica de sondaje vesical (SV) en pacientes mayores, y si el SV está asociado a una evolución más compleja o grave. METODO: Se incluyeron todos los pacientes de edad 65 años atendidos durante una semana en 52 servicios de urgencias (SU) españoles, que fueron clasificados en función de si se practicó o no SV en el SU. Se investigó la relación de SV con edad, sexo, 10 variables de comorbilidad, 7 de estado basal y 6 de situación clínica mediante un modelo de regresión logística multivariable. Se consideró la evolución como grave o compleja si existió necesidad de hospitalización, estancia prolongada, necesidad de residencia al alta o muerte. La relación entre edad y SV se exploró también mediante curvas spline cúbicas restringidas (SCR) ajustadas, tomando la edad de 65 años como referencia. RESULTADOS: Se incluyeron 24.573 pacientes, de los que 976 (4%) recibieron SV. De éstos, el 44,3% fueron dados de alta desde urgencias. De las 25 variables exploradas, 15 se relacionaron independientemente con el SV, y las más manifiestas fueron disminución de consciencia (OR = 2,50, IC 95% = 1,90-3,30), deshidratación (OR = 2,24, IC 95% = 1,85-2,72) y sexo masculino (OR = 2,12, IC 95% = 1,84-2,44). La edad 80 años también se asoció a SV (OR = 1,17, IC 95% = 1,01-1,358), y las curvas SCR ajustadas mostraron un incremento progresivo y lineal de la probabilidad de SV con la edad, constante en hombres y que se estabilizaba a partir de los 85 años en mujeres (p interacción 0,001). El SV se asoció a necesidad de hospitalización (OR = 2,31, IC 95% = 1,99-2,68), hospitalización en intensivos (OR = 4,64, IC 95% = 3,04-7,09), estancia prolongada en urgencias en los pacientes dados de alta (OR = 2,28, IC 95% = 1,75-2,96) y mortalidad intrahospitalaria (OR = 1,99, IC 95% = 1,54-2,57) y a 30 días (OR=1,66, IC 95% = 1,33-2,08), pero no con hospitalización prolongada (OR = 1,11, IC 95% = 0,92-1,34) ni con necesidad de residencia al alta (OR = 1,50, IC 95% = 0,98-2,29). CONCLUSIONES: Determinadas características del paciente mayor y de su estado clínico se asocian con realizar un SV en urgencias, entre las que destacan la disminución de consciencia, la deshidratación y el sexo masculino. Aun teniendo en cuenta los factores asociados a SV en urgencias, este procedimiento se asocia independientemente con evoluciones más complejas o graves.

Pathology in Practice.

In collaboration with the American College of Veterinary Pathologists.

HIV Transmembrane Glycoprotein Conserved Domains and Genetic Markers Across HIV-1 and HIV-2 Variants.

HIV envelope transmembrane glycoproteins gp41 (HIV-1) and gp36 (HIV-2) present high variability and play a key role in the HIV-host cell membrane's fusion, as a target for human broadly neutralizing antibodies (bnAbs) and drugs. Thus, a better knowledge of amino acid (aa) conservation across structural domains and HIV variants can help to identify conserved targets to direct new therapeutic and diagnostic strategies. All available gp41/gp36 nucleotide sequences were downloaded from Los Alamos National Laboratory (LANL) HIV Sequence Database, selecting 17,078 sequences ascribed to HIV-1 and HIV-2 variants with ≥3 sequences. After aligning and translating into aa with MEGAv6.0, an in-house bioinformatics program (EpiMolBio) was used to identify the most conserved aa and the aa changes that were specific for each variant (V-markers) vs. HXB2/BEN (HIV-1/HIV-2) reference sequence. We analyzed the presence of specific aa changes among V-markers affecting infectivity, gp41 structure, function, or resistance to the enfuvirtide viral fusion inhibitor (T-20). We also inferred the consensus sequences per HIV variant, describing in each HIV-1 group (M, N, O, P) the conservation level along the complete gp41 per structural domain and locating in each binding site the anti-gp41 human Abs (bnAbs and non bnAbs) described in LANL. We found 38.3/59.7% highly conserved aa present in ≥90% of the 16,803/275 gp41/gp36 sequences ascribed to 105/3 HIV-1/HIV-2 variants, with 9/12.6% of them showing complete conservation across LANL sequences. The fusion peptide, its proximal region, the N-heptad repeat, and the membrane-proximal external region were the gp41 domains with ≥84% of conserved aa in the HIV-1 consensus sequence, the target of most Abs. No natural major resistance mutations to T-20 were observed. Our results show, for the first time, a complete conservation study of gp41/gp36 per variant in the largest panel of HIV variants analyzed to date, providing useful information for a more rational design of drugs, vaccines, and molecular detection tests targeting the HIV transmembrane glycoprotein.

Mechanical Behavior of Calcium Sulphate Modified with Citric Acid and with Added Carbon Fibers.

The study and subsequent analysis of the interaction of calcium sulfate with added citric acid and with two additional proportions of carbon fibers of different lengths has been based on the IMR and D Method for its realization. The purpose of this work is the study of the physical and mechanical behavior of the resulting material between the intimate mixture of calcium sulfate with additives and carbon fibers, justifying said work with a link to the Sustainable Development Goals (SDG) regarding the benefits that the Calcium sulfate has contributed to civil society since times dating back to ancient Egypt. We find ourselves with a material of which the energy used in its manufacture is far from that required by steel or cement, and construction with this new compound is in a much higher stage than construction with adobe. Therefore, this is a compound that can be developed for a wide variety of applications. The novelty of this study is the inclusion of polymeric fibers in a material used over the centuries to improve its mechanical properties. With these improvements we will be able to reduce thicknesses in manufacturing, which implies a reduction in manufacturing energy and weight structures in buildings, which should be studied and analyzed in the future. The kneading of calcium sulfate with long fibers at high percentages complicates not only the results, but also the manufacturing process. As representative results of the study, we can indicate that a composite material with high mechanical capacity has been achieved, with maximum values of flexural strength of 8.12 N/mm2 and compression strength of 17.58 N/mm2.

Relationship between the Antifungal Activity of Chitosan-Capsaicin Nanoparticles and the Oxidative Stress Response on Aspergillus parasiticus.

The fungus Aspergillus parasiticus is a contaminant in agricultural crops and its eradication involves the indiscriminate use of harmful synthetic pesticides. In the search for antifungal agents of natural origin, chitosan (Q) and capsaicin (C) are coupled in the form of nanoparticles (Np), which can possess a direct application under specific conditions. Due to their small size, Np can cross through the cell wall, taking the cells into a pro-oxidant environment known as "oxidative stress", which presents when the reactive oxygen species (ROS) surpass the number of antioxidants in the cell. In the present investigation, nanoparticles of chitosan (Np Q) and nanoparticles of chitosan-capsaicin (Np QC) with an average diameter of 44.8 ± 20.6 nm and 111.1 ± 14.1 nm, respectively, were synthesized, and there was a zeta potential of + 25.6 ± 0.7 mV and + 26.8 ± 6.1 mV, respectively. The effect of the concentration of Np Q (A, B, C, and D), of Np QC (A, B, C, and D), and capsaicin in a solution (control) was evaluated on the viability of the spores, the accumulation of intracellular ROS, and the morphometric changes of A. parasiticus. Acute toxicity of the Np was determined utilizing bioassays with Artemia salina, and acute phytotoxicity was evaluated in lettuce seeds (Lactuca sativa). According to ROS results, capsaicin (control) did not induce oxidative stress in the cell; otherwise, it was observed to have an elevated (p < 0.05) accumulation of ROS when the concentration of Np Q increased. For both, Np Q and Np QC, an inverse physiological pattern relating spore viability and ROS accumulation in the fungus was found; the viability of spores decreased as the ROS accumulation increased. The spore viability of A. parasiticus diminished upon increasing the concentration of chitosan (0.3−0.4 mg/mL) in the Np, while the intracellular accumulation of ROS increased proportionally to the concentration of the nanomaterials in the treatments of Np Q and Np QC. On the other hand, Np QC presented a lower (p < 0.05) toxicological effect in comparison with Np Q, which indicates that the incorporation of bioactive compounds, such as capsaicin, into nanoparticles of chitosan is a strategy that permits the reduction of the toxicity associated with nanostructured materials.

Comparing an e-Health program vs home rehabilitation program in patients with non-specific low back pain: A study protocol randomized feasibility trial.

BACKGROUND: There is little evidence on the reliability of the web application-based rehabilitation systems to treat chronic low back pain (CLBP). METHODS: This protocol describes a double-blind, randomized controlled feasibility trial of an e-Health intervention developed to support the self-management of people with CLBP in primary care physiotherapy. Three Hospitals with primary care for outpatients will be the units of randomisation, in each Hospital the participants will be randomized to one of two groups, a pragmatic control group receiving either the usual home program based on electrostimulation and McKenzie Therapy and e-Health intervention. Patients are followed up at 2 and 6 months. The primary outcomes are (1) acceptability and demand of the intervention by GPs, physiotherapists and patients and (2) feasibility and optimal study design/methods for a definitive trial. Secondary outcomes will include analysis in the clinical outcomes of pain, disability, fear of movement, quality of life, isometric resistance of the trunk flexors, lumbar anteflexion and lumbar segmental range of motion. DISCUSSION: The specific e-Health programs to home could increase adherence to treatment, prevent stages of greater pain and disability, and improve the painful symptomatology. CONCLUSIONS: The e-Health programs could be an effective healthcare tool that can reach a large number of people living in rural or remote areas.

Antioxidant Effect of Nanoparticles Composed of Zein and Orange (Citrus sinensis) Extract Obtained by Ultrasound-Assisted Extraction.

In the present research, an orange extract (OE) was obtained and encapsulated in a zein matrix for its subsequent physicochemical characterization and evaluation of its antioxidant capacity. The OE consists of phenolic compounds and flavonoids extracted from orange peel (Citrus sinensis) by ultrasound-assisted extraction (UAE). The results obtained by dynamic light scattering (DLS) and scanning electron microscopy (SEM) indicated that zein nanoparticles with orange extract (NpZOE) presented a nanometric size and spherical shape, presenting a hydrodynamic diameter of 159.26 ± 5.96 nm. Furthermore, ζ-potential evolution and Fourier transform infrared spectroscopy (FTIR) techniques were used to evaluate the interaction between zein and OE. Regarding antioxidant activity, ABTS and DPPH assays indicated no significant differences at high concentrations of orange peel extract and NpZOE; however, NpZOE was more effective at low concentrations. Although this indicates that ultrasonication as an extraction method effectively obtains the phenolic compounds present in orange peels, the nanoprecipitation method under the conditions used allowed us to obtain particles in the nanometric range with positive ζ-potential. On the other hand, the antioxidant capacity analysis indicated a high antioxidant capacity of both OE and the NpZOE. This study presents the possibility of obtaining orange extracts by ultrasound and coupling them to zein-based nanoparticulate systems to be applied as biomedical materials functionalized with antioxidant substances of pharmaceutical utility.

Course of infection with the emergent pathogen Brucella microti in immunocompromised mice.

A new Brucella species, Brucella microti, has been isolated from wild rodents and found to be pathogenic in mice. The biological relevance of this new mouse pathogen is clear, as it allows us to study Brucella infection in a species-specific model. The course of infection in wild-type (wt) and immunodeficient mice that lack B (Jh), T and B (SCID), or T, B, and NK (SCID.Beige) cells was analyzed over 3 weeks. wt mice completely cleared bacteria from the liver and spleen after that time. However, SCID mice showed a much higher bacterial load in the spleen and liver than wt and Jh mice after 1 week and maintained the same level during the next 2 weeks. All mice tested survived for the 3 weeks. In contrast, the bacterial levels in mice that lacked NK cell activity progressively increased and these mice succumbed to infection after 16 to 18 days. Histopathology analysis of infected mice showed extensive areas of necrotic tissue and thrombosis in liver after 1 week in all infected SCID.Beige mice but were not seen in either SCID or wt animals. These processes were dramatically increased after 21 days, corresponding with the death of SCID.Beige animals. Our results indicate that T and/or B cells are required for the control of infection with the mouse pathogen Brucella microti in liver and spleen but that NK cells are crucial for survival in the absence of B and T cells. In addition, they suggest that controlled granuloma formation is critical to clear this type of infection in wt mice.

Dictyostatin flexibility bridges conformations in solution and in the ß-tubulin taxane binding site.

Dictyostatin (DCT, 1) is a complex, flexible polyketide macrolide that demonstrates potent microtubule-polymerization activity. Both a solution structure (2a) and a possible binding mode for DCT (Conf-1) have been proposed by earlier NMR experiments. In the present study, the conformational landscape of DCT in DMSO-d(6) and methanol-d(4) was explored using extensive force-field-based conformational searches combined with geometric parameters derived from solution NMR data. The results portray a diversity of conformations for dictyostatin that illustrates the molecule's flexibility and excludes the previously suggested dominant solution conformation 2a. One conformation present in DMSO-d(6) with a 7% population (Conf-2, 0.6 kcal/mol above the global minimum at 298°) also satisfies the TR-NOESY NMR parameters of Canales et al. that characterize the taxane binding-site interaction between DCT and assembled microtubules in water. Application of several docking methods (Glide, Autodock, and RosettaLigand) has identified a low-energy binding model of the DCT/ß-tubulin complex (Pose-2/Conf-2) that is gratifyingly compatible with the emerging DCT structure-activity data.

Role of FIP200 in cardiac and liver development and its regulation of TNFalpha and TSC-mTOR signaling pathways.

Focal adhesion kinase family interacting protein of 200 kD (FIP200) has been shown to regulate diverse cellular functions such as cell size, proliferation, and migration in vitro. However, the function of FIP200 in vivo has not been investigated. We show that targeted deletion of FIP200 in the mouse led to embryonic death at mid/late gestation associated with heart failure and liver degeneration. We found that FIP200 knockout (KO) embryos show reduced S6 kinase activation and cell size as a result of increased tuberous sclerosis complex function. Furthermore, FIP200 KO embryos exhibited significant apoptosis in heart and liver. Consistent with this, FIP200 KO mouse embryo fibroblasts and liver cells showed increased apoptosis and reduced c-Jun N-terminal kinase phosphorylation in response to tumor necrosis factor (TNF) alpha stimulation, which might be mediated by FIP200 interaction with apoptosis signal-regulating kinase 1 (ASK1) and TNF receptor-associated factor 2 (TRAF2), regulation of TRAF2-ASK1 interaction, and ASK1 phosphorylation. Together, our results reveal that FIP200 functions as a regulatory node to couple two important signaling pathways to regulate cell growth and survival during mouse embryogenesis.