The superposed electric field effect on the charge transport and polaron formation in molecular crystals.

We study the polaron formation and its mobility in a one-dimensional molecular crystal subjected to superposed static and harmonic electric fields. Such molecular chain exhibits intermolecular vibrational degrees of freedom, which makes the carrier-lattice interaction an important parameter of the system. By exploring field settings in which the preferential transport occurs, we show the existence of different small polaron formations, including those that travel close to the sound velocity or that are stationary by self-trapping. Electric fields magnitudes and carrier-lattice coupling have also been analyzed, which allowed to show a phase diagram that describes the existing regimes. In addition to thresholds between the mobile and stationary polaron regimes, this phase diagram unveils an unusual aspect: a metastable polaron formation.

Beneficial Effects of Soluble Guanylyl Cyclase Stimulation and Activation in Sickle Cell Disease Are Amplified by Hydroxyurea: In Vitro and In Vivo Studies.

The complex pathophysiology of sickle cell anemia (SCA) involves intravascular hemolytic processes and recurrent vaso-occlusion, driven by chronic vascular inflammation, which result in the disease's severe clinical complications, including recurrent painful vaso-occlusive episodes. Hydroxyurea, the only drug frequently used for SCA therapy, is a cytostatic agent, although it appears to exert nitric oxide/soluble guanylyl cyclase (sGC) modulating activity. As new drugs that can complement or replace the use of hydroxyurea are sought to further reduce vaso-occlusive episode frequency in SCA, we investigated the effects of the sGC agonists BAY 60-2770 (sGC activator) and BAY 41-2272 (sGC stimulator) in the presence or absence of hydroxyurea on SCA vaso-occlusive mechanisms and cell recruitment both ex vivo and in vivo. These agents significantly reduced stimulated human SCA neutrophil adhesive properties ex vivo in association with the inhibition of surface ß2-integrin activation. A single administration of BAY 60-2770 or BAY 41-2272 decreased tumor necrosis factor cytokine-induced leukocyte recruitment in a mouse model of SCA vaso-occlusion. Importantly, the in vivo actions of both agonists were significantly potentiated by the coadministration of hydroxyurea. Erythroid cell fetal hemoglobin (HbF) elevation is also a major goal for SCA therapy. BAY 41-2272 but not BAY 60-2770 at the concentrations employed significantly induced γ-globin gene transcription in association with HbF production in cultured erythroleukemic cells. In conclusion, sGC agonist drugs could represent a promising approach as therapy for SCA, for use either as stand-alone treatments or in combination with hydroxyurea. SIGNIFICANCE STATEMENT: This preclinical study demonstrates that stimulators and activators of sGC are potent inhibitors of the adhesion and recruitment of leukocytes from humans and in mice with sickle cell anemia (SCA) and may represent a promising approach for diminishing vaso-occlusive episode frequency in SCA. Hydroxyurea, a drug already frequently used for treating SCA, was found to potentiate the beneficial effects of sGC agonists in in vivo studies, implying that these classes of compounds could be used alone or in combination therapy.

Photocatalytic degradation of swine wastewater on aqueous TiO2 suspensions: optimization and modeling via Box-Behnken design.

Heterogeneous photocatalysis is a promising technology to treat many industrial wastewaters. To date, this potential has not been proven with wastewaters from agricultural origins, such as swine wastewater. In this work, the photocatalytic degradation of swine wastewater was studied by applying a response surface methodology based on the Box-Behnken design. The interactive effects of the variation of factors such as photocatalyst dosage (X1), wastewater concentration (X2), and irradiation time (X3) were analyzed to identify the optimal operating conditions for COD reduction. A second-order polynomial accurately represented organics degradation with a high adjusted R-squared (0.9666). The main effects of factor X2 and the quadratic effects of factors X2 and X3 were the most significant for COD reduction. The optimal conditions for COD degradation were 1.16 g L-1 for photocatalyst dosage, 1.68% for wastewater concentration, and irradiation time of 9.2 h. These results have been validated in a confirmation experiment and COD removal reached 91.7% (98.1 % predicted). Based on the Langmuir-Hinshelwood model, the reaction rate constant was 3.9×10-3 min-1. Besides, FTIR analysis indicated that Aeroxide® TiO2 reusability may be possible, especially for low wastewater concentrations. Heterogeneous photocatalysis can be applied as a technology for the integrated treatment of industrial wastewaters resulting from swine production.

Evaluation of the risk of diabetic peripheral neuropathy: Design and validation of the NeuDiaCan nursing screening procedure. / Valoración del riesgo de neuropatía periférica diabética: diseño y validación del procedimiento para cribado enfermero NeuDiaCan.

OBJECTIVE: To design and validate a nursing screening procedure for diabetic peripheral neuropathy in primary care. METHODS: The study was carried out in three phases. 1)Construction of an item bank to form the procedure with an exit score describing the patient's clinical situation. 2)Test and reduction of the initial tentative procedure on a sample of 50 patients using community nurse consultations, eliminating the components with low inter-intra nurse reliability. 3)Validation of the version of the procedure obtained in the previous step on a sample of 106 patients. Calculation of validity and reliability by eliminating components with low criterion validity with respect to the results of the diagnostic electromyography used as a reference standard. Cut-off points were estimated for the use of the procedure as a screening tool, predictive values, performance, internal consistency and inter-nurse reliability. RESULTS: The initial tentative procedure consisted of 12 components that were reduced to 10. In the process of validation of this second version the procedure was simplified again, eventually comprising 6 components, with a cut-off point of 2.5 in its output scale, the point at which it reaches adequate values of sensitivity and negative predictors to be used as a screening instrument. For this cut-off point the inter-intra nurse reliability, criterion validity and predictive validity reached acceptable values. CONCLUSIONS: NeuDiaCan as a nursing screening procedure for diabetic peripheral neuropathy in primary care is valid, reliable and easy to use.

Socio-environmental profile of child and adolescents sensitized by house dust mite in northeast of Brazil.

INTRODUCTION: The association regarding the atopic sensitization to mite aeroallergens and the socio-environmental features is still inconsistent. OBJECTIVES: We analyzed the role played by socioeconomic and environmental factors in the prevalence of sensitization to house dust mite (HDM) allergens, and associated with the risk of developing asthma symptoms. PATIENTS AND METHODS: This is a case-control study conducted with 108 patients, aged 1-17. We inquired about family habits, socioeconomic and environmental features. We applied the International Study of Asthma and Allergies in Childhood questionnaire. RESULTS: We observed patients sensitized to all HDM tested, Derp (42%), Derf (37%) and Blot (33%). Middle family income (OR: 2.74; CI95%: 1.127-6.684), exposure to dog (OR: 3.758, CI95%: 1.127-6.684) and artificial climatization (OR: 4.319, CI95%: 1.398-13.348) were associated with sensitization to Derp. We also observed protective factors, such as sharing of dormitories, washing cycle for bedspreads and the presence of basic sanitation. An increased risk of sensitization to Derf was associated with Blot sensitization (OR: 3.172, CI95%: 1.083-9.292) and presence of mold on the walls (OR: 3.095, CI95%: 1.063-9.008). A protective factor was dormitory sharing. For sensitization to Blot, we observed an increase in the risk associated with Derp sensitization (OR: 3.462, CI95%: 1.191-10.061) and exposure to dog (OR: 3.255, CI95%: 0.987-10.736). In addition, sensitization to Blot increases the risk of developing asthma symptoms (OR: 2.732, CI95%: 0.981-7.606). CONCLUSION: Our data show distinct sociodemographic and environmental relations that lead to HDM sensitization and increased probability of development of allergic diseases.

The Grieving Nursing Diagnoses in the Primary Healthcare Setting.

PURPOSE: To estimate the prevalence of Grieving, risk for Complicated Grieving, and Complicated Grieving in the primary care setting. METHODS: Retrospective epidemiological study, analyzing data from electronic health records (EHR). FINDINGS: A total of 84% of the 9,063 records had diagnostic labels without defining characteristics, related factors, or risk factors. A larger frequency of complicated grieving was found in deceased mourners. CONCLUSIONS: The grieving epidemiology opens new chances for the research using data from EHR. PRACTICE IMPLICATIONS: The adequacy of the records is essential to develop a profile of the patient at risk of complications after the loss. This research is an important step to build an epidemiological basis for nursing diagnosis of grieving in the primary health care setting.

Antigenic response to CT-P13 and infliximab originator in inflammatory bowel disease patients shows similar epitope recognition.

AIM: To test the cross-immunogenicity of anti-CT-P13 IBD patients' sera to CT-P13/infliximab originator and the comparative antigenicity evoked by CT-P13/infliximab originator sera. METHODS: Sera of patients with IBD with measurable anti-CT-P13 antibodies were tested for their cross-reactivity to 5 batches of infliximab originator and CT-P13. Anti-drug antibody positive sera from treated patients were used to compare antigenic epitopes. RESULTS: All 42 anti-CT-P13 and 37 anti-infliximab originator IBD sera were cross-reactive with infliximab originator and CT-P13 respectively. Concentration of anti-drug antibodies against infliximab originator or CT-P13 were strongly correlated both for IgG1 and IgG4 (P < 0.001). Anti-CT-P13 sera of patients with IBD (n = 32) exerted similar functional inhibition on CT-P13 or infliximab originator TNF binding capacity and showed reduced binding to CT-P13 in the presence of five different batches of CT-P13 and infliximab originator. Anti-CT-P13 and anti-infliximab originator IBD sera selectively enriched phage-peptides from the VH (CDR1 and CDR3) and VL domains (CDR2 and CDR3) of infliximab. Sera reactivity detected major infliximab epitopes in these regions of infliximab in 60%-79% of patients, and no significant differences were identified between CT-P13 and infliximab originator immunogenic sera. Minor epitopes were localised in framework regions of infliximab with reduced antibody reactivity shown, in 30%-50% of patients. Monoclonal antibodies derived from naïve individuals and ADA-positive IBD patients treated with CT-P13 provided comparable epitope specificity to five different batches of CT-P13 and infliximab originator. CONCLUSIONS: These results strongly support a similar antigenic profile for infliximab originator and CT-P13, and point toward a safe switching between the two drugs in anti-drug antibody negative patients.

Body fluid identification using a targeted mRNA massively parallel sequencing approach - results of a EUROFORGEN/EDNAP collaborative exercise.

In a previous study we presented an assay for targeted mRNA sequencing for the identification of human body fluids, optimised for the Illumina MiSeq/FGx MPS platform. This assay, together with an additional in-house designed assay for the Ion Torrent PGM/S5 platform, was the basis for a collaborative exercise within 17 EUROFORGEN and EDNAP laboratories, in order to test the efficacy of targeted mRNA sequencing to identify body fluids. The task was to analyse the supplied dried body fluid stains and, optionally, participants' own bona fide or mock casework samples of human origin, according to specified protocols. The provided primer pools for the Illumina MiSeq/FGx and the Ion Torrent PGM/S5 platforms included 33 and 29 body fluid specific targets, respectively, to identify blood, saliva, semen, vaginal secretion, menstrual blood and skin. The results demonstrated moderate to high count values in the body fluid or tissue of interest with little to no counts in non-target body fluids. There was some inter-laboratory variability in read counts, but overall the results of the laboratories were comparable in that highly expressed markers showed high read counts and less expressed markers showed lower counts. We performed a partial least squares (PLS) analysis on the data, where blood, menstrual blood, saliva and semen markers and samples clustered well. The results of this collaborative mRNA massively parallel sequencing (MPS) exercise support targeted mRNA sequencing as a reliable body fluid identification method that could be added to the repertoire of forensic MPS panels.

A GHEP-ISFG collaborative study on the genetic variation of 38 autosomal indels for human identification in different continental populations.

A collaborative effort was carried out by the Spanish and Portuguese Speaking Working Group of the International Society for Forensic Genetics (GHEP-ISFG) to promote knowledge exchange between associate laboratories interested in the implementation of indel-based methodologies and build allele frequency databases of 38 indels for forensic applications. These databases include populations from different countries that are relevant for identification and kinship investigations undertaken by the participating laboratories. Before compiling population data, participants were asked to type the 38 indels in blind samples from annual GHEP-ISFG proficiency tests, using an amplification protocol previously described. Only laboratories that reported correct results contributed with population data to this study. A total of 5839 samples were genotyped from 45 different populations from Africa, America, East Asia, Europe and Middle East. Population differentiation analysis showed significant differences between most populations studied from Africa and America, as well as between two Asian populations from China and East Timor. Low FST values were detected among most European populations. Overall diversities and parameters of forensic efficiency were high in populations from all continents.

Abnormal mortality of octopus after a storm water event: Accumulated lead and lead isotopes as fingerprints.

Octopus vulgaris is a sedentary organism that inhabits coastal waters being exposed to anthropogenic compounds. Lead concentration in coastal environments reflects many processes and activities namely weathering, industrial and domestic discharges, and atmospheric deposition. Since lead isotopic composition is little affected by kinetic processes occurring between source and sink, its signature has been used to identify different Pb sources. After a short-term heavy rainfall, hundreds of octopus appeared dead in two Portuguese coastal areas. Histopathology and Pb levels and its stable isotopes were determined in tissues, such as digestive gland, of stranded octopus and compared to alive specimens, sediments and runoff material from the same areas. Histology results showed severe damage in stranded octopus tissues suggesting that death was probably associated to multiple organ failure linked to hypertrophy and exudates input. In addition, Pb in stranded specimens reach concentrations up to one order of magnitude above the levels reported for alive octopus. Pb isotopic signatures in stranded organisms were closer to runoff material pointing to a similar origin of Pb. In summary, the results in this study showed that a short-term runoff event might change abruptly the salinity leading to the disruption of the osmoregulation function of octopus and consequently leading to its death. The analyses of stable isotopic Pb signature in octopus tissues corroborate these results and points to a change in the Pb source due to runoff after the storm water event. Pb stable isotopes in octopus proved to be an adequate tool to confirm the cause of death and linking it to the environment conditions.

Position Paper from the Portuguese Association of Hospital Pharmacists for biosimilar therapeutic antibodies.

WHAT IS KNOWN AND OBJECTIVE: Biopharmaceuticals are an important class of drugs for the treatment of autoimmune/inflammatory and oncologic diseases. With patent expiries, biotechnological manufacturers can now develop biosimilar drugs. Due to timeliness of introducing new and more complex biosimilars, the Portuguese Association of Hospital Pharmacists gathered to develop a common positioning on the use of biosimilar monoclonal antibodies. MAIN ISSUES: The European pathway to biosimilar approval was developed to improve affordability and access to biological therapies, but it remains a work in progress because unresolved issues remain. Due to the present reality of biosimilar monoclonal antibodies, hospital pharmacists must play an important role in ensuring the safe, effective and cost-effective use of biosimilars in health systems; and educating healthcare administrators, providers, legislators, policymakers, payors and patients about these products. WHAT IS NEW AND CONCLUSION: The conclusions presented in this work focused on the proposal for optimal biosimilar prescription criteria, the preparation of original biologics and biosimilars in the pharmacy, the management and selection of suppliers, extrapolation issues, the specific role of pharmacovigilance and risk management for the optimal use of biosimilar monoclonal antibodies.

Influence of bioaccessibility of total mercury, methyl-mercury and selenium on the risk/benefit associated to the consumption of raw and cooked blue shark (Prionace glauca).

This study aimed to identify the benefit and risk associated with raw and cooked blue shark consumption taking into account the bioaccessibility of Se, Hg and MeHg, by using in vitro digestion method. Selenium, Hg and MeHg levels were higher in cooked samples, particularly in grilled blue shark. Whereas Se bioaccessibility was above 83% in grilled samples, Hg and MeHg bioaccessibility was lower in grilled samples with values near 50%. In addition, all Se-Health Beneficial Values were negative and the molar MeHg:Se ratios were higher than one. The risk-benefit assessment yielded a maximum consumption of one yearly meal for raw or cooked blue shark, thus emphasizing the need to recommend the consumption of a wider variety of seafood species in a balanced and healthy diet.

Detection of Toxoplasma gondii DNA in Brazilian oysters (Crassostrea rhizophorae).

The aim of this study was to detect evidence of Toxoplasma gondii using polymerase chain reaction (PCR)-based techniques in oysters (Crassostrea rhizophorae) obtained from the southern coastal region of Bahia, Brazil. A total of 624 oysters were collected, and the gills and digestive glands were dissected. Each tissue sample was separated into pools containing tissues (of the same type) from three animals, leading to a total of 416 experimental samples for analysis (208 samples each from the gills and digestive glands). Molecular analysis using PCR-based detection of the T. gondii AF 146527 repetitive fragment yielded negative results for all samples. However, when nested-PCR was used for detection of the T. gondii SAG-1 gene, 17 samples were positive, with the gills being the tissue with maximal detection of the parasite. These positive results were confirmed by sample sequencing. It is therefore suggested that C. rhizophorae oysters are capable of filtering and retaining T. gondii oocysts in their tissue. This represents a risk to public health because they are traditionally ingested in natura.

[Immune reconstitution inflammatory syndrome related with infliximab interruption in patient with Crohn's disease and active tuberculosis]. / Síndrome de reconstituição imune associado à interrupção do infliximab em doente com doença de Crohn e tuberculose activa.

Tumor necrosis factor alpha inhibitors are associated with an increased risk of active tuberculosis. However, its interruption in this setting may trigger a paradoxical response to tuberculosis treatment, as an immune reconstitution inflammatory syndrome. We present the case of a 36-year-old patient, with Crohn's disease, treated with infliximab for the last 8 years, who was admitted with miliary tuberculosis. A pan-susceptible Mycobacterium tuberculosis strain was isolated. Infliximab was interrupted and standard antituberculous therapy was started, as well as systemic corticotherapy, without any clinical or radiological improvement. After exclusion of other opportunistic infections and primary or acquired immunodeficiency, we considered the possibility of an immune reconstitution inflammatory syndrome triggered by infliximab interruption. Thus, infliximab was reintroduced after 2 months of antituberculous therapy and clinical and radiological improvement was observed.