Hybrid Methacrylated Gelatin and Hyaluronic Acid Hydrogel Scaffolds. Preparation and Systematic Characterization for Prospective Tissue Engineering Applications.

Hyaluronic acid (HA) and gelatin (Gel) are major components of the extracellular matrix of different tissues, and thus are largely appealing for the construction of hybrid hydrogels to combine the favorable characteristics of each biopolymer, such as the gel adhesiveness of Gel and the better mechanical strength of HA, respectively. However, despite previous studies conducted so far, the relationship between composition and scaffold structure and physico-chemical properties has not been completely and systematically established. In this work, pure and hybrid hydrogels of methacroyl-modified HA (HAMA) and Gel (GelMA) were prepared by UV photopolymerization and an extensive characterization was done to elucidate such correlations. Methacrylation degrees of ca. 40% and 11% for GelMA and HAMA, respectively, were obtained, which allows to improve the hydrogels' mechanical properties. Hybrid GelMA/HAMA hydrogels were stiffer, with elastic modulus up to ca. 30 kPa, and porous (up to 91%) compared with pure GelMA ones at similar GelMA concentrations thanks to the interaction between HAMA and GelMA chains in the polymeric matrix. The progressive presence of HAMA gave rise to scaffolds with more disorganized, stiffer, and less porous structures owing to the net increase of mass in the hydrogel compositions. HAMA also made hybrid hydrogels more swellable and resistant to collagenase biodegradation. Hence, the suitable choice of polymeric composition allows to regulate the hydrogels´ physical properties to look for the most optimal characteristics required for the intended tissue engineering application.

Hydrogeochemical baseline in a human-altered landscape of the central Pacific coast of Costa Rica.

Groundwater pollution in tropical and human-altered coastal landscapes is receiving novel attention due to decreasing in annual recharge as a consequence of recurrent droughts and overexploitation, whereby saline intrusion, point and diffuse source contamination, and water conflicts are common denominators. This study presents a detailed groundwater evaluation in a coastal aquifer within the central Pacific coast of Costa Rica. Three sampling campaigns including major ions, heavy metals, and fecal coliform analyses were conducted between July 2013 and March 2014 across 17 wells within the alluvial and fissured units of the Jacó aquifer. The groundwater system is classified as mixed HCO3--Ca2+-Mg2+ type. Coliforms presence was found in two wells, nearby Mona Creek headwaters and near the coastal line. Heavy metal concentrations were below quantification limits in most of the wells; however, chromium concentrations up to 6.56 µg/L were quantified within the coastal line and central portion of the alluvial aquifer in 20 out of the 48 samples. The spatial distribution of major ions (K+, Na+, Ca2+, Mg2+, Cl-, SO42-, and HCO3-) exhibited an increasing trend towards the central portion of the alluvial aquifer, which may be potentially associated with the large unregulated urban expansion, invoking a need of a continuous water quality monitoring program in this touristic hot spot. This study provides useful information for other similar coastal aquifers in Central America, whereby increasing population growth and unregulated touristic, industrial, and agricultural activities are posing a truly challenge to ensure water security and sustainability parallel to the economic development in a changing climate.

Impulsive Source of the 2017 MW=7.3 Ezgeleh, Iran, Earthquake.

On 12 November 2017, a M W=7.3 earthquake struck near the Iranian town of Ezgeleh, at the Iran-Iraq border. This event was located within the Zagros fold and thrust belt which delimits the continental collision between the Arabian and Eurasian Plates. Despite a high seismic risk, the seismogenic behavior of the complex network of active faults is not well documented in this area due to the long recurrence interval of large earthquakes. In this study, we jointly invert interferometric synthetic aperture radar and near-field strong motions to infer a kinematic slip model of the rupture. The incorporation of these near-field observations enables a fine resolution of the kinematic rupture process. It reveals an impulsive seismic source with a strong southward rupture directivity, consistent with significant damage south of the epicenter. We also show that the slip direction does not match plate convergence, implying that some of the accumulated strain must be partitioned onto other faults.

Pharmacokinetic variations of nimesulide in mongrel dogs according to age.

The purpose of this research was to investigate the possible variations to the pharmacokinetics of nimesulide by the effect of age using an animal model. An experimental, analytical, prospective and longitudinal study in five dogs, from birth to 730 days of age was carried out. Nimesulide blood levels were measured in different months; concentrations were determined by HPLC-UV. Pharmacokinetic parameters were calculated by using the WinNonlin software. There were statistically significant differences (p <0.05) in most of the pharmacokinetic parameters between study of 6 months against the other three studies in different ages. Changes in the pharmacokinetic parameters of nimesulide as a result of age, are determined by the growing and maturation of the animals. Resulting data suggest that nimesulide can be used safely as a long-term analgesic in dogs, but, the dosing regimens in humans should be different when administered at early age.

Cystatin B and HIV regulate the STAT-1 signaling circuit in HIV-infected and INF-ß-treated human macrophages.

Cystatin B is a cysteine protease inhibitor that induces HIV replication in monocyte-derived macrophages (MDM). This protein interacts with signal transducer and activator of transcription (STAT-1) factor and inhibits the interferon (IFN-ß) response in Vero cells by preventing STAT-1 translocation to the nucleus. Cystatin B also decreases the levels of tyrosine-phosphorylated STAT-1 (STAT-1PY). However, the mechanisms of cystatin B regulation on STAT-1 phosphorylation in MDM are unknown. We hypothesized that cystatin B inhibits IFN-ß antiviral responses and induces HIV replication in macrophage reservoirs through the inhibition of STAT-1 phosphorylation. Macrophages were transfected with cystatin B siRNA prior to interferon-ß treatment or infected with HIV-ADA to determine the effect of cystatin B modulation in STAT-1 localization and activation using immunofluorescence and proximity ligation assays. Cystatin B decreased STAT-1PY and its transportation to the nucleus, while HIV infection retained unphosphorylated STAT (USTAT-1) in the nucleus avoiding its exit to the cytoplasm for eventual phosphorylation. In IFN-ß-treated MDM, cystatin B inhibited the nuclear translocation of both, USTAT-1 and STAT-1PY. These results demonstrate that cystatin B interferes with the STAT-1 signaling and IFN-ß-antiviral responses perpetuating HIV in macrophage reservoirs.

Electroconvulsive therapy as a treatment for refractory neuropsychiatric lupus with catatonia: three case studies and literature review.

Neuropsychiatric disorders associated with systemic lupus erythematosus are very common. Treatment generally consists of glucocorticoids and immunosuppressive therapy; however, some cases are unresponsive. Electroconvulsive therapy (ECT) is a recognized treatment modality in psychiatry and is an option for refractory cases of neuropsychiatric lupus. This report describes three cases of neuropsychiatric lupus that improved with ECT after failure of antipsychotics and immunosuppressive therapy. All cases met DSM-5 criteria for catatonia (case 1: agitation, stereotypies, and grimacing; case 2: stupor, mutism, and grimacing; case 3: agitation, mutism, and stereotypies); therefore, ECT was indicated. This case series shows that ECT can be a therapeutic option in patients with neuropsychiatric lupus, especially when associated with catatonia and unresponsive to conventional treatment.

Collective optical Kerr effect exhibited by an integrated configuration of silicon quantum dots and gold nanoparticles embedded in ion-implanted silica.

The study of the third-order optical nonlinear response exhibited by a composite containing gold nanoparticles and silicon quantum dots nucleated by ion implantation in a high-purity silica matrix is presented. The nanocomposites were explored as an integrated configuration containing two different ion-implanted distributions. The time-resolved optical Kerr gate and z-scan techniques were conducted using 80 fs pulses at a 825 nm wavelength; while the nanosecond response was investigated by a vectorial two-wave mixing method at 532 nm with 1 ns pulses. An ultrafast purely electronic nonlinearity was associated to the optical Kerr effect for the femtosecond experiments, while a thermal effect was identified as the main mechanism responsible for the nonlinear optical refraction induced by nanosecond pulses. Comparative experimental tests for examining the contribution of the Au and Si distributions to the total third-order optical response were carried out. We consider that the additional defects generated by consecutive ion irradiations in the preparation of ion-implanted samples do not notably modify the off-resonance electronic optical nonlinearities; but they do result in an important change for near-resonant nanosecond third-order optical phenomena exhibited by the closely spaced nanoparticle distributions.

Effective qPCR methodology to quantify the expression of virulence genes in Aeromonas salmonicida subsp. salmonicida.

AIMS: This study aimed to select and validate different methodological strategies to quantify the expression of the virulence genes ascC and ascV by qPCR in Aeromonas salmonicida subsp. salmonicida (Aer. salmonicida). METHODS AND RESULTS: Using the geNorm, Normfinder and BestKeeper algorithms, reference genes for the qPCR were selected based on their in vitro expression stabilities in three Aer. salmonicida strains. Gene amplification efficiency was calculated by Real-time PCR Miner and LinReg PCR programmes, which have not been used previously in the analysis of bacterial gene expression. The expression of the ascC and ascV virulence genes in a virulent Aer. salmonicida strain was evaluated by three quantification models, including single (least or most stable) or three most stable reference genes, combined with constant or specific gene amplification efficiency. The most stable reference genes were gyrB, proC and rpoC, while rpoD and fabD were the least stable. Quantification models showed different expression patterns. CONCLUSIONS: The optimal strategy to quantify mRNA expression was to use a combination of the three algorithms and the quantification model including the three most stable reference genes. Real-time PCR Miner or LinReg PCR were valuable tools to estimate amplification efficiency. SIGNIFICANCE AND IMPACT OF THE STUDY: The methods used in this study gave more reliable expression data using qPCR than previously published methods. The quantification and expression dynamics of virulence genes will contribute to a better understanding of how Aer. salmonicida interacts with its host and the environment, and therefore to the prevention of epizootics due to this pathogen.

A unified perspective on the nature of bonding in pairwise interatomic interactions.

Different classes of ground electronic state pairwise interatomic interactions are referenced to a single canonical potential using explicit transformations. These approaches have been applied to diatomic molecules N2, CO, H2(+), H2, HF, LiH, Mg2, Ca2, O2, the argon dimer, and one-dimensional cuts through multidimensional potentials of OC-HBr, OC-HF, OC-HCCH, OC-HCN, OC-HCl, OC-HI, OC-BrCl, and OC-Cl2 using accurate semiempirically determined interatomic Rydberg-Klein-Rees (RKR) and morphed intermolecular potentials. Different bonding categories are represented in these systems, which vary from van der Waals, halogen bonding, and hydrogen bonding to strongly bound covalent molecules with binding energies covering 3 orders of magnitude from 84.5 to 89,600.6 cm(-1) in ground state dissociation energies. Such approaches were then utilized to give a unified perspective on the nature of bonding in the whole range of diatomic and intermolecular interactions investigated.

Evaluation of Water Sanitation Health Education Programme: Working with the Knowledge of the Basic Sanitation Services in a Developing Community in Rural Haiti after the 2010 Earthquake.

OBJECTIVE: The aim of this study is to measure the knowledge regarding the new sanitation water system being implemented in Dessources, a rural community in the municipality of Croix-des-Bouquets in Haiti after a two-year intervention programme. DESIGN AND METHODS: A cross-sectional epidemiologic design was used to measure the knowledge of the people in the community using a semi-structured questionnaire. Data collection followed a face-to-face interview process in all houses of the community. The instrument content validity was performed by a panel of experts followed by Cronbach's alpha test to establish the reliability of knowledge scale. In addition, association measures were done using Stata 11.0 statistical package. RESULTS: Content validity test were performed with minimum changes and an alpha of 0.74 was obtained for the scale. Response rate was 65.57% (41/60 houses); non-participants were only those who did not meet the inclusion criteria. Most of the participants (77.5%) were 21-49 years old and 85% had been living in the community for more than 20 years. Bivariate analysis showed that the people of Dessources had adequate knowledge. Significant differences, however, were found among the zones that are not in use of the new sanitary systems and among families with more than seven members per house. CONCLUSIONS: Differences found can be explained based on the Rogers theoretical diffusion of innovation model. The evaluation shows that people of Dessources in Haiti have a high knowledge regarding the new water sanitation system and provided evidence of an adequate health education programme intervention.

Brachytherapy versus radical hysterectomy after external beam chemoradiation with gemcitabine plus cisplatin: a randomized, phase III study in IB2-IIB cervical cancer patients.

BACKGROUND: The aim of the present study was to demonstrate that radical hysterectomy (RH) leads to improved survival outcomes in FIGO stage IB2-IIB cervical cancer when compared with standard brachytherapy (BCT) after identical external beam chemoradiation (EBRT-CT). PATIENTS AND METHODS: EBRT-CT treatment consisted of six courses of cisplatin at 40 mg/m² and gemcitabine at 125 mg/m² per week concurrent with 50.4 Gy of radiation. In the BCT arm, EBRT-CT was followed by BCT to reach a point A dose of 85 Gy, whereas in the experimental arm, a type III RH with bilateral pelvic lymph node dissection and para-aortic lymph node sampling (RH) was carried out within 4-6 weeks after EBRT-CT. RESULTS: Between May 2004 and June 2009, 211 patients were enrolled (BCT, 100 and RH, 111). At a median follow-up time of 36 months (3-80), progression-free survival (PFS) and overall survival (OS) rates were similar in both the arms. PFS rates were 74.8% and 71.7% in the BCT and RH arms [HR 0.6516 (95% confidence interval (CI) 0.3504-1.2116)], P = 0.186. OS rates were 76.3% in the BCT versus 74.5% in the surgical arm [HR 0.6981 (95% CI 0.3106-1.3439)], P = 0.236. No differences were observed in the pattern of local and systemic failures. CONCLUSIONS: This study failed to demonstrate that RH after EBRT-CT is superior to standard BCT.

[Prevention, diagnosis and treatment of bleeding in cardiac surgery]. / Prevención, diagnóstico y tratamiento de la hemorragia en cirugía cardiaca.

Patients undergoing cardiac surgery are at high risk of bleeding and transfusion. This risk has increased in recent years and is associated with increased morbidity and mortality. Moreover, despite being one of the most common complications associated with this surgery, there remains a large variability in its management between institutions. Implementation of algorithms for coagulation management has been shown to reduce transfusion requirements and therefore it seems essential to establish protocols that include preventive measures, effective mechanisms for diagnosis and treatment algorithms. On the other hand, the emergence of new drugs and the use of point of care coagulation monitoring systems, is changing our diagnostic and therapeutic options. This paper reviews several aspects related to the causes, diagnosis and treatment of bleeding associated with cardiac surgery and presents an algorithm for its management.

[Psychometric validation of a guideline for classifying the medical complexity of children and adolescents with special health care needs]. / Validación psicométrica de Pauta de Clasificación de Complejidad Médica de niños, niñas y adolescentes con Necesidades Especiales de Atención en Salud.

Children and youth with special health care needs (CYSHCN) present an intensive use of health services resources and demand a high level of coordination between these services, communities, and families. SOCHIPE, along with other experts, generated a Complexity Classification Guideline to allocate resources according to the need of the cases through the Health Care Network. OBJECTIVE: To perform a construct validation of the Complexity Classification Guideline. SUBJECTS AND METHOD: With a sample of 488 CYSHNC to whom the Classification Guideline was applied, an instrument reliability analysis was performed, in addition to an exploratory and confirmatory factor analysis. RESULTS: The Classification Guideline obtained a standardized Cronbach's Alpha of 0.87; however, the RMSEA, TLI, and CFI model fit statistics were lower than expected. The MI coefficient suggested the elimination of 9 items, from which a summary Guideline of 11 items and three dimensions was generated that presented an RMSEA of 0.60; TLI of 0.970, and CFI of 0.977. CONCLUSION: The study allows us to have a Summarized Complexity Classification Guideline for CYSHNC, with good psychometric properties, quick application, and easy interpretation, for application in the public health network.

Tai chi as an adjunctive therapy for individuals who plateau after vestibular rehabilitation.

OBJECTIVE: This study aimed to evaluate the effectiveness of tai chi on balance in patients with improved but persistent dizziness and imbalance following completion of traditional vestibular rehabilitation therapy. METHOD: Patients who completed vestibular rehabilitation therapy with persistent imbalance were prospectively enrolled in a tai chi programme comprising eight weekly classes. Balance was assessed before the first and after the eighth session using the Dynamic Gait Index, Activities-Specific Balance Confidence scale and Dizziness Handicap Inventory. RESULTS: A total of 37 participants (34 females, 3 males) completed the programme with balance testing. Mean age was 76.8 years (range, 56-91 years). Mean Dynamic Gait Index significantly increased after completion of tai chi (p < 0.00001). Mean Activities-Specific Balance Confidence scale score increased from 63.6 to 67.9 per cent (p = 0.046). A subset (n = 18) of patients completed a Dizziness Handicap Inventory without significant post-therapeutic change (p = 0.62). Most (36 of 37; 97.3 per cent) patients demonstrated post-therapy improvement on one or more assessments. CONCLUSION: Tai chi is a viable adjunct to improve balance in patients who complete a vestibular rehabilitation therapy programme.

Inhibition of interferon response by cystatin B: implication in HIV replication of macrophage reservoirs.

Cystatin B and signal transducer and activator of transcription-1 (STAT-1) phosphorylation have recently been shown to increase human immunodeficiency virus-1 (HIV-1) replication in monocyte-derived macrophages (MDM), but the molecular pathways by which they do are unknown. We hypothesized that cystatin B inhibits the interferon (IFN) response and regulates STAT-1 phosphorylation by interacting with additional proteins. To test if cystatin B inhibits the IFN-ß response, we performed luciferase reporter gene assays in Vero cells, which are IFN deficient. Interferon-stimulated response element (ISRE)-driven expression of firefly luciferase was significantly inhibited in Vero cells transfected with a cystatin B expression vector compared to cells transfected with an empty vector. To determine whether cystatin B interacts with other key players regulating STAT-1 phosphorylation and HIV-1 replication, cystatin B was immunoprecipitated from HIV-1-infected MDM. The protein complex was analyzed by liquid chromatography tandem mass spectrometry. Protein interactions with cystatin B were verified by Western blots and immunofluorescence with confocal imaging. Our findings confirmed that cystatin B interacts with pyruvate kinase M2 isoform, a protein previously associated cocaine enhancement of HIV-1 replication, and major vault protein (MVP), an IFN-responsive protein that interferes with JAK/STAT signals. Western blot studies confirmed the interaction with pyruvate kinase M2 isoform and MVP. Immunofluorescence studies of HIV-1-infected MDM showed that upregulated MVP colocalized with STAT-1. To our knowledge, the current study is the first to demonstrate the coexpression of cystatin B, STAT-1, MVP, and pyruvate kinase M2 isoform with HIV-1 replication in MDM and thus suggests novel targets for HIV-1 restriction in macrophages, the principal reservoirs for HIV-1 in the central nervous system.

Role of Rhizobium endoglucanase CelC2 in cellulose biosynthesis and biofilm formation on plant roots and abiotic surfaces.

BACKGROUND: The synthesis of cellulose is among the most important but poorly understood biochemical processes, especially in bacteria, due to its complexity and high degree of regulation. In this study, we analyzed both the production of cellulose by all known members of the Rhizobiaceae and the diversity of Rhizobium celABC operon predicted to be involved in cellulose biosynthesis. We also investigated the involvement in cellulose production and biofilm formation of celC gene encoding an endoglucanase (CelC2) that is required for canonical symbiotic root hair infection by Rhizobium leguminosarum bv. trifolii. RESULTS: ANU843 celC mutants lacking (ANU843ΔC2) or overproducing cellulase (ANU843C2+) produced greatly increased or reduced amounts of external cellulose micro fibrils, respectively. Calcofluor-stained cellulose micro fibrils were considerably longer when formed by ANU843ΔC2 bacteria rather than by the wild-type strain, in correlation with a significant increase in their flocculation in batch culture. In contrast, neither calcofluor-stained extracellular micro fibrils nor flocculation was detectable in ANU843C2+ cells. To clarify the role of cellulose synthesis in Rhizobium cell aggregation and attachment, we analyzed the ability of these mutants to produce biofilms on different surfaces. Alteration of wild-type CelC2 levels resulted in a reduced ability of bacteria to form biofilms both in abiotic surfaces and in planta. CONCLUSIONS: Our results support a key role of the CelC2 cellulase in cellulose biosynthesis by modulating the length of the cellulose fibrils that mediate firm adhesion among Rhizobium bacteria leading to biofilm formation. Rhizobium cellulose is an essential component of the biofilm polysaccharidic matrix architecture and either an excess or a defect of this "building material" seem to collapse the biofilm structure. These results position cellulose hydrolytic enzymes as excellent anti-biofilm candidates.

Late recurrence of cervical cancer: a report of 16 cases.

PURPOSE: To analyze the clinical characteristics and outcome of cervical cancer patients presenting late recurrence. MATERIALS AND METHODS: The medical records of 16 patients who were treated between 1974 and 1999 at the Institution and whose cancer recurred after a five-year disease-free interval were reviewed. RESULTS: Mean time from initial therapy to recurrence was 162.5 months (60-360 mean). Smear abnormalities, atypical genital bleeding, abdominal and lumbar pain, and respiratory findings were the most common symptoms and signs associated with late recurrence. Fourteen patients were diagnosed by physical examination. Three of the six patients with local recurrence who were re-irradiated developed a vesico-vaginal fistula. At a median follow-up time of 12.5 months (4-38 mean), 12 patients were alive and the median survival time was 30 months. CONCLUSIONS: Cervical cancer patients surviving free of disease after the fifth year post-treatment are still at risk for relapse and in most of them, the recurrence is suspected by clinical examination alone.

Hemispheric resource availability influences face perception: a multiple resource approach to social perception.

Two experiments tested the hypothesis that social perception recruits distinct limited-capacity processing resources that are distinguished by the cerebral hemispheres. To test this hypothesis, social perception efficiency was assessed after relevant hemispheric processing resources were depleted. In Experiment 1 prime faces were unilaterally presented for 30 ms, after which centrally presented target faces were categorised by sex. In Experiment 2 prime faces were unilaterally presented for 80 ms after which centrally presented target faces were categorised by fame. Results showed that sex categorisation was slower after primes were presented in the right versus left visual field, and that fame categorisation was slower after familiar primes were presented in the left versus right visual field. The results support a multiple resource account of social perception in which the availability of resources distributed across the cerebral hemispheres influences social perception.

Polymerization of aniline hydrochloride in reverse of microemulsion by batch and semicontinuous process using ionic and nonionic surfactants.

The polymerization of aniline hydrochloride by inverse microemulsion in a batch process and the semicontinuous process was studied as a function of the surfactant ionic and nonionic. Polymerizations were carried out at 60°C for 4 h with a yield polymer of circa 67 and 27% wt. for ionic and nonionic surfactants. The conductivity of synthesized polyaniline by the semicontinuous process is higher up to three orders of magnitude than that of the batch process for both surfactants. The calculating degree of oxidation by UV-Vis showed the relative intensities of the quinoid to benzenoid unit around one. The morphology was determined by Scanning Electron Microscopy (SEM) and observed that the formation of the different morphologies is due to the self-assembly behavior of surfactant. The diameter z-average particle size (Dz) was studied by Transmission Electron Microscopy (TEM), which determined that the diameter particle in a semicontinuous state is larger than the one produced in a batch; this is due to the control of monomer addition in the system. These findings suggest that the polymerization process and the type of surfactant influence the properties of polyaniline.

Ultrafast nonlinear optical response of photoconductive ZnO films with fluorine nanoparticles.

The absorptive and refractive third order nonlinear optical properties exhibited by a ZnO thin solid film with fluorine nanoparticles were studied with picosecond and femtosecond pulses using different techniques. We were able to evaluate the photoconductivity of the material and the quenching of the induced birefringence observed in the presence of two-photon absorption. The samples were prepared by a chemical spray deposition technique. In order to investigate the different contributions of the third order nonlinearities of the film, we analyzed the vectorial self-diffraction effect and the optical Kerr transmittance observed in the sample. A dominantly absorptive nonlinearity was measured at a 532 nm wavelength with 50 ps pulses, while nonlinear refraction was found to be negligible in this regime. On the other side, a pure electronic refractive third order nonlinearity without the contribution of nonlinear absorption was detected at 830 nm with 80 fs pulse duration. A quasi-instantaneous optical response and a strong enhancement in the ultrafast nonlinear refraction with the inhibition of the picosecond two-photon absorption mechanism were measured for the case of the femtosecond excitation.