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A indústria mineral tem compromissos permanentes e inadiáveis com a sustentabilidade. O setor representa um rico campo de análise sobre o encontro entre as racionalidades econômica e ambiental. Justamente pela magnitude das escalas em que as mineradoras atuam e de seus impactos socioambientais, e por operarem sob pesadas pressões que incidem no mercado global de commodities, importa compreender essa evolução recente no setor. Em paralelo, é imperativo construir indicadores para monitorar a sustentabilidade em regiões que abrigam grandes minas. Este artigo discute os diversos aspectos do desenvolvimento sustentável e analisa as categorias propostas de indicadores de sustentabilidade na mineração, com base em literatura recente. A partir daí, propõe um conjunto de indicadores de sustentabilidade para a mineração industrial, nos eixos ambiental, econômico e social, com aderência a regiões tropicais, entre as quais a Província Mineral de Carajás, localizada na região sudeste do estado do Pará (Amazônia, Brasil).

A Estrada de Ferro Carajás (EFC), de 900km, escoa os minérios do sudeste do Pará ao porto de São Luís, no Maranhão. As comunidades lindeiras têm maus indicadores sociais e carências de políticas públicas. Para conhecer a rede institucional desse território, foi entrevistada uma amostra de 17 líderes de associações comunitárias e instituições parceiras. A rede mostrou-se esparsa, com poucos elos de alta centralidade e reduzidos fluxos de fontes externas até as comunidades locais, limitando sua capacidade de articulação coletiva e de desenvolvimento. Daí, possivelmente, a eclosão de conflitos como forma de expressão. O fortalecimento de uma rede densa e diversa por parte de stakeholders locais poderá transformar o caráter de “redes de resistência” contra impactos adversos, para “redes de colaboração” no desenvolvimento sustentável.

Inborn metabolic errors (IME) and cortical developmental malformations are uncommon etiologies of neonatal seizures, however they may represent treatable causes of refractory epilepsy and for this reason must be considered as possible etiological factors. This case report aims to demonstrate the importance of neuroimaging studies in one patient with neonatal seizures, even when there are clues pointing to a metabolic disorder. CASE REPORT: A previously healthy 14 day-old child started presenting reiterated focal motor seizures (FMS) which evolved to status epilepticus. Exams showed high serum levels of ammonia and no other abnormalities. A metabolic investigation was conducted with normal results. During follow-up, the patient presented developmental delay and left side hemiparesia. Seizures remained controlled with anti-epileptic drugs for four months, followed by relapse with repetitive FMS on the left side. Temporary improvement was obtained with anti-epileptic drug adjustment. At the age of 6 months, during a new episode of status epilepticus, high ammonia levels were detected. Other metabolic exams remained normal. The child was referred to a video-electroencephalographic monitoring and continuous epileptiform discharges were recorded over the right parasagittal and midline regions, with predominance over the posterior quadrant. A new neuroimaging study was performed and displayed a malformation of cortical development. Our case illustrates that because newborns are prone to present metabolic disarrangement, an unbalance such as hyperammonemia may be a consequence of acute events and conduct to a misdiagnosis of IME.

Estudamos seis pacientes com acidúria glutárica tipo I, em quatro famílias. Observamos variações intensas na apresentação clínica, mesmo entre elementos da mesma família. Três pacientes evoluiram sem alterações até o início das anomalias neurológicas, que se manifestaram como encefalite-símile, no primeiro ano de vida. Uma criança apresentou atraso precoce do desenvolvimento, sem episódios agudos de descompensação. Dois pacientes não têm alteração cognitiva; um deles apresenta leve tremor associado a quadro coreoatetóide desde o primeiro ano de vida, enquanto o outro teve apenas duas crises convulsivas afebris quando lactente. Três crianças apresentam distonia como sequela, não sendo capazes de sentar ou firmar a cabeça. Os seis pacientes apresentam macrocrania e a neles tomografia computatorizada de crânio demonstra aumento dos espaços liquóricos em regiões fronto-temporais. O estudo dos ácidos orgânicos urinários dos pacientes demonstra elevação dos níveis do ácido glutárico.

Abstract Background Heterokont algae, together with cryptophytes, haptophytes and some alveolates, possess red-algal derived plastids. The chromalveolate hypothesis proposes that the red-algal derived plastids of all four groups have a monophyletic origin resulting from a single secondary endosymbiotic event. However, due to incongruence between nuclear and plastid phylogenies, this controversial hypothesis remains under debate. Large-scale genomic analyses have shown to be a powerful tool for phylogenetic reconstruction but insufficient sequence data have been available for red-algal derived plastid genomes. Results The chloroplast genomes of two brown algae, Ectocarpus siliculosus and Fucus vesiculosus, have been fully sequenced. These species represent two distinct orders of the Phaeophyceae, which is a major group within the heterokont lineage. The sizes of the circular plastid genomes are 139,954 and 124,986 base pairs, respectively, the size difference being due principally to the presence of longer inverted repeat and intergenic regions in E. siliculosus. Gene contents of the two plastids are similar with 139-148 protein-coding genes, 28-31 tRNA genes, and 3 ribosomal RNA genes. The two genomes also exhibit very similar rearrangements compared to other sequenced plastid genomes. The tRNA-Leu gene of E. siliculosus lacks an intron, in contrast to the F. vesiculosus and other heterokont plastid homologues, suggesting its recent loss in the Ectocarpales. Most of the brown algal plastid genes are shared with other red-algal derived plastid genomes, but a few are absent from raphidophyte or diatom plastid genomes. One of these regions is most similar to an apicomplexan nuclear sequence. The phylogenetic relationship between heterokonts, cryptophytes and haptophytes (collectively referred to as chromists) plastids was investigated using several datasets of concatenated proteins from two cyanobacterial genomes and 18 plastid genomes, including most of the available red algal and chromist plastid genomes. Conclusion The phylogenetic studies using concatenated plastid proteins still do not resolve the question of the monophyly of all chromist plastids. However, these results support both the monophyly of heterokont plastids and that of cryptophyte and haptophyte plastids, in agreement with nuclear phylogenies.

Abstract Background Occupational and chronic exposure to solvents and metals is considered a possible risk factor for Parkinson's disease and essential tremor. While manufacturing dental prostheses, dental technicians are exposed to numerous chemicals that contain toxins known to affect the central nervous system, such as solvents (which contain n-hexane in particular) and metals (which contain mercury, iron, chromium, cobalt and nickel). Methods We performed an epidemiological and clinical study on all 27 dental technicians working in a school for dental technicians. We asked all the technicians to fill in a self-administered questionnaire on extrapyramidal symptoms, and the General Health Questionnaire (GHQ), a self-administered screening instrument, to detect any psychiatric disorders. Moreover, we invited all 27 dental technicians to undergo a neurological examination and provide a detailed occupational history in our clinic. Results Of the 14 subjects who underwent the neurological examination, four had postural tremor and one had a diagnosis of Parkinson's disease. Conclusion We found a high prevalence of extrapyramidal signs and symptoms in this group of male dental technicians working in a state technical high school in Rome. We believe that this finding may be due to the presence of toxins in the dental technician's work.

Abstract Background Apoptosis has recently been proposed to contribute to the pathogenesis of emphysema. Methods In order to establish if cell fate plays a role even in end-stage disease we studied 16 lungs (9 smoking-associated and 7 α1antitrypsin (AAT)-deficiency emphysema) from patients who had undergone lung transplantations. Six unused donor lungs served as controls. Apoptosis was evaluated by TUNEL analysis, single-stranded DNA laddering, electron microscopy and cell proliferation by an immunohistochemical method (MIB1). The role of the transforming growth factor (TGF)-β1 pathway was also investigated and correlated with epithelial cell turnover and with the severity of inflammatory cell infiltrate. Results The apoptotic index (AI) was significantly higher in emphysematous lungs compared to the control group (p ≤ 0.01), particularly if only lungs with AAT-deficiency emphysema were considered (p ≤ 0.01 vs p = 0.09). The proliferation index was similar in patients and controls (1.9 ± 2.2 vs 1.7 ± 1.1). An increased number of T lymphocytes was observed in AAT-deficiency lungs than smoking-related cases (p ≤ 0.05). TGF-β1 expression in the alveolar wall was higher in patients with smoking-associated emphysema than in cases with AAT-deficiency emphysema (p ≤ 0.05). A positive correlation between TGF-βRII and AI was observed only in the control group (p ≤ 0.005, r2 = 0.8). A negative correlation was found between the TGF-β pathway (particularly TGF-βRII) and T lymphocytes infiltrate in smoking-related cases (p ≤ 0.05, r2 = 0.99) Conclusion Our findings suggest that apoptosis of alveolar epithelial cells plays an important role even in end-stage emphysema particularly in AAT-deficiency disease. The TGFβ-1 pathway does not seem to directly influence epithelial turnover in end-stage disease. Inflammatory cytokine different from TGF-β1 may differently orchestrate cell fate in AAT and smoking-related emphysema types.

Background/objectives: The unique properties of iron oxide nanoparticles have attracted significant interest within the biomedical community, particularly for magnetic hyperthermia applications. Various synthesis methods have been developed to optimize these nanoparticles., Methods: In this study, we employed a powdered coconut water (PCW)-assisted sol-gel method to produce magnetite nanoparticles for the first time. A comprehensive analysis of the thermal (differential thermal analysis and thermogravimetry), structural (X-ray diffraction), morphological (scanning electron microscopy with energy dispersive spectroscopy), magnetic (vibrating sample magnetometer and hyperthermia), and biological (cytotoxicity essays) properties was conducted to assess their potential for magnetic hyperthermia., Results: Samples heat-treated at 700 °C and 400 °C (washed powder) for 4 h under argon presented only magnetite in their composition. The micrometer-sized particles exhibited ferrimagnetic behavior, with saturation magnetization values of 37, 76, and 10 emu/g and specific absorption rates (SAR) of 27.1, 19.9, and 14.1 W/g, respectively, for treatments at 350 °C (48 h), 700 °C (4 h), and 400 °C (washed powder, 4 h) under an argon atmosphere. Biological tests showed no cytotoxicity below 10 mg/mL., Conclusions: The findings highlight the potential of PCW-assisted synthesis as a sustainable and efficient strategy for producing pure magnetite, with powder washing preceding the heat treatment enabling the attainment of this phase at lower temperatures. Nevertheless, the micrometer-scale dimensions is observed in the morphological analysis limit their suitability for biomedical applications.

An increasing number of projects require the precise knowledge and control of thermal conditions within the study system and their temporal evolution. This is particularly critical for equipment such as laboratory ovens and microbiological incubators, which are essential in various fields of chemistry and microbiology areas. These devices allow and facilitate the execution of experimental work in controlled environments, leading to reproducible experiments. This work presents a methodology for assembling and calibrating a highly accessible and low-cost data logger equipped with multiple temperature sensors. The final calibrated dispositive is straightforward to construct and allows the simultaneous and independent temperature measurement from multiple positions within the same system, which is then applied to the study, characterization, control, and monitoring of the internal thermal behavior of a laboratory oven dedicated to microbiological agents' cultivation. This approach ensures, through a robust methodology, a precise characterization by quantitative methods that allows objective decision making in the management and control of the temperature inside the system. Additionally, the device is suitable for extension and application in diverse research environments by modifying the sensor calibration to achieve a desired temperature range or number of measurement units, representing a potential work tool for laboratory systems.

Cancer is a major worldwide public health problem. Although there have already been astonishing advances in cancer diagnosis and treatment, the scientific community continues to make huge efforts to develop new methods to treat cancer. The main objective of this work is to prepare, using a green sol-gel method with coconut water powder (CWP), a new nanocomposite with a mixture of Gd 3 Fe 5 O 12 and ZnFe 2 O 4 , which has never been synthesized previously. Therefore, we carried out a structural (DTA-TG and X-ray diffraction), morphological (SEM), and magnetic (VSM and hyperthermia) characterization of the prepared samples. The prepared nanocomposite denoted a saturation magnetization of 11.56 emu/g at room temperature with a ferromagnetic behavior and with a specific absorption rate (SAR) value of 0.5 ± 0.2 (W/g). Regarding cytotoxicity, for concentrations < 10 mg/mL, it does not appear to be toxic. Although the obtained results were interesting, the high particle size was identified as a problem for the use of this nanocomposite.

Purpose: Limited data exist regarding the surgical outcomes of acute colonic pseudo-obstruction (ACPO), commonly referred to as Ogilvie syndrome, in modern clinical practice. The prevailing belief is that surgery should be avoided due to previously reported high mortality rates. We aimed to describe the surgical results of ACPO treated within our institution., Methods: Our prospectively maintained colorectal surgery registry was queried for patients diagnosed with ACPO, who underwent surgery between 2009 and 2022. Postoperative complications were graded according to Clavien-Dindo (CD) classification. The primary outcome was postoperative mortality., Results: A total of 32 patients who underwent surgery for ACPO were identified. Overall, nonoperative therapy was initially administered to 21 patients (65.6%). The surgeries performed included total abdominal colectomy (15, 43.1%), ascending colectomy with end ileostomy (8, 25%), transverse colostomy (5, 15.6%), ileostomy and transverse colostomy (3, 9.4%), and Hartmann's operation (1, 3.1%). Severe postoperative complications (CD grade 3 or 4) occurred in five patients (15.6%). No recurrence of ACPO was observed and no patient required reoperation. The average postoperative length of stay was 14.5 days, 30-day mortality was 6.3% (n = 2), and 90-day mortality was 15.6% (n = 5) due to complications of underlying comorbidities., Conclusions: Surgical treatment was effective for patients with ACPO refractory to medical therapy or presenting with acute complications. Although postoperative complications were frequent, both the 30- and 90-day mortality rates were lower than previously documented in the literature. Further investigations are warranted to determine the optimal surgical strategy, which may involve total or segmental colectomy, or diversion alone without resection., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Cancer is one of the leading causes of death worldwide. Conventional treatments such as surgery, chemotherapy, and radiotherapy have limitations and severe side effects. Magnetic hyperthermia (MH) is an alternative method that can be used alone or in conjunction with chemotherapy or radiotherapy to treat cancer. Cobalt ferrite particles were synthesized using an innovative biogenic sol-gel method with powder of coconut water (PCW). The obtained powders were subjected to heat treatments between 500 °C and 1100 °C. Subsequently, they were characterized by thermal, structural, magnetic, and cytotoxic analyses to assess their suitability for MH applications. Through X-ray diffraction and Raman spectroscopy, it was possible to confirm the presence of the pure phase of CoFe 2 O 4 in the sample treated at 1100 °C, exhibiting a saturation magnetization of 84 emu/g at 300 K and an average grain size of 542 nm. Furthermore, the sample treated at 1100 °C showed a specific absorption rate (SAR) of 3.91 W/g, and at concentrations equal to or below 5 mg/mL, is non-cytotoxic, being the most suitable for biomedical applications.

The non-surgical treatments are being required to reconstruct damaged tissue, prioritizing our body's natural healing process. Thus, the use of bioactive materials such as bioactive glass has been studied to support the repair and restoration of hard and soft tissue. Thus, in this work Bioglass 45S5 was developed, adding 1 and 2%mol of SrO or MgO and the physical and biological properties were evaluated. The addition of MgO and SrO at the studied concentrations promoted the slight increase in non-bridging oxygens number, observed through the temperature shift in phase transitions to lower values compared to Bioglass 45S5. The insertion of the ions also showed a positive effect on Saos-2 cell viability, decreasing the cytotoxic of Bioglass 45S5. Besides the Ca/P ratio on the pellets surface demonstrating no evidence of higher reactivity between Bioglass 45S5 and Bioglass with Sr and Mg, micrographs show that at 24 h the Ca/P rich layer is denser than in Bioglass 45S5 after the contact with simulated body fluid. The samples with Sr and Mg show a higher antibacterial effect compared to Bioglass 45S5. The addition of the studied ions may benefit the biological response of Bioglass 45S5 in dental applications as scaffolds or coatings.

La 0.67 Ca 0.2 Ba 0.13 Fe 1- x Ti x O 3 samples ( x = 0 and 0.03) were synthesized by the auto-combustion method. Analysis of XRD diffractograms revealed that these compounds crystallize in the cubic system with the space group Pm 3̄ m . The dielectric properties have been studied in the 10 2 -10 6 frequency range and the 120-280 K temperature range. Analysis of AC conductivity shows that the conduction mechanisms are of polaronic origin and that they are co-dominated by the NSPT and OLPT models. The monotonic increase in conductivity with increasing temperature results from the reduction of defect centers and the increase in charge carrier mobility. Such variation is consistent with impedance variation at different frequencies and temperatures indicating semiconductor behavior. Nyquist diagrams are characterized by the appearance of semi-circular arcs. These spectra are modeled in terms of equivalent electrical circuits confirming the contribution of grains ( R g //CPE g ) and grain boundaries ( R gb //CPE gb ). The dielectric analysis showed an evolution of the dielectric constant in accordance with Koop's theory and the phenomenological model of Maxwell-Wagner. The low conductivity and the high values of the real permittivity at low frequency make our compounds potential candidates for energy storage and applications for electronic devices and microwaves., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (This journal is © The Royal Society of Chemistry.)

Biofilm-related implant infections pose a substantial threat to patients, leading to inflammation in the surrounding tissue, and often resulting in implant loss and the necessity for additional surgeries. Overcoming this implantology challenge is crucial to ensure the success and durability of implants. This study shows the development of antibacterial materials for implant coatings by incorporating copper into 45S5 Bioglass ® . By combining the regenerative properties of Bioglass ® with the antimicrobial effects of copper, this material has the potential to prevent infections, enhance osseointegration and improve the long-term success of implants. Bioglasses modified with various concentrations of CuO (from 0 to 8 mol%) were prepared with the melt-quenching technique. Structural analysis using Raman and FTIR spectroscopies did not reveal significant alterations in the bioglasses structure with the addition of Cu. The antibacterial activity of the samples was assessed against Gram-positive and Gram-negative bacteria, and the results demonstrated significant inhibition of bacterial growth for the bioglass with 0.5 mol% of CuO. Cell viability studies indicated that the samples modified with up to 4 mol% of CuO maintained good cytocompatibility with the Saos-2 cell line at extract concentrations up to 25 mg/mL. Furthermore, the bioactivity assessment demonstrated the formation of a calcium phosphate (CaP)-rich layer on the surfaces of all bioglasses within 24 h. Our findings show that the inclusion of copper in the bioglass offers a significant enhancement in its potential as a coating material for implants, resulting in notable advancements in both antibacterial efficacy and osteointegration properties.

Implantology is crucial for restoring aesthetics and masticatory function in oral rehabilitation. Despite its advantages, certain issues, such as bacterial infection, may still arise that hinder osseointegration and result in implant rejection. This work aims to address these challenges by developing a biomaterial for dental implant coating based on 45S5 Bioglass ® modified by zirconium insertion. The structural characterization of the glasses, by XRD, showed that the introduction of zirconium in the Bioglass network at a concentration higher than 2 mol% promotes phase separation, with crystal phase formation. Impedance spectroscopy was used, in the frequency range of 10 2 -10 6 Hz and the temperature range of 200-400 K, to investigate the electrical properties of these Bioglasses, due to their ability to store electrical charges and therefore enhance the osseointegration capacity. The electrical study showed that the presence of crystal phases, in the glass ceramic with 8 mol% of zirconium, led to a significant increase in conductivity. In terms of biological properties, the Bioglasses exhibited an antibacterial effect against Gram-positive and Gram-negative bacteria and did not show cytotoxicity for the Saos-2 cell line at extract concentrations up to 25 mg/mL. Furthermore, the results of the bioactivity test revealed that within 24 h, a CaP-rich layer began to form on the surface of all the samples. According to our results, the incorporation of 2 mol% of ZrO 2 into the Bioglass significantly improves its potential as a coating material for dental implants, enhancing both its antibacterial and osteointegration properties.

Ferrite compounds have recently attracted significant interest because of their multifunctional properties. This work investigates the optical, magnetic, and dielectric properties of a LiMn 0.5 Fe 2 O 4 ferrite prepared by a solid-state reaction. Raman spectroscopy analysis substantiated the presence of the 5 active modes representing the vibration of the oxygen anion at both tetrahedral and octahedral sites. The direct optical band gap was estimated to be 3.51 eV, which indicates the semiconductor behavior of the compound. A theoretical modulation of the hysteresis loop was done to confirm the dominance of the ferromagnetic contribution over the antiferromagnetic one. Furthermore, the dielectric permittivity result indicated a colossal value of the order of 10 3 . The dielectric losses are characterized by the Giuntini law to extract the relaxation process, which is hidden by the DC-conductivity process. Our results indicate the potential of LiMn 0.5 Fe 2 O 4 for applications in multifunctional devices., Competing Interests: The authors declare that there are no competing interests regarding the publication of this paper., (This journal is © The Royal Society of Chemistry.)

Purpose: Colorectal cancer patients are commonly considered a single entity in outcomes studies. This is particularly true for quality of life (QOL) studies. This study aims to compare oncologic and QOL outcomes between right colon, left colon, and rectal cancer in patients operated on in a single high-volume institution., Methods: A prospectively maintained database was queried to identify patients with pathological stages I-III colorectal adenocarcinoma electively operated on with curative intent between 2000 and 2010. Patient characteristics, perioperative and oncologic outcomes, and QOL were compared according to cancer location., Results: Two-thousand sixty-five (606 right colon cancer [RCC], 366 left colon cancer [LCC], and 1093 rectal cancer [RC]) patients met the inclusion criteria. LCC had better overall survival (OS) and disease-free survival (DFS) in the non-adjusted analysis (p < 0.001) and better OS in multivariate analysis adjusted by age, gender, ASA, chemotherapy, and pathological stage (p = 0.024). Although RCC had worse OS and DFS in non-adjusted survival analysis than LCC and RC, when adjusted for the factors above, RCC had better survival outcomes than RC, but not LCC. COX regression analysis showed age (p < 0.001), gender (p = 0.016), ASA (p < 0.001), pathological stage (p < 0.001), adjuvant chemotherapy (p = 0.043), and cancer location (p = 0.024) were independently associated with OS. Age (p < 0.001), gender (p = 0.030), ASA (p = 0.004), and pathological stage (p < 0.001) were independently associated with DFS. Patients with RC reported more sexual dysfunction and work restrictions than colon cancers (p = 0.015 and p < 0.001, respectively)., Conclusion: In an adjusted multivariate analysis, colon cancers demonstrated better survival outcomes when compared to rectal cancers., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

In this work we synthesized the multifunctional (La 0.8 Ca 0.2 ) 0.4 Bi 0.6 FeO 3 material using a sol-gel process. Structural and morphologic investigations reveal a Pnma perovskite structure at room temperature with spherical and polygonal nanoparticles. A detailed study of the temperature dependence of the dielectric and electrical properties of the studied material proves a typical FE-PE transition with a colossal value of real permittivity at 350 K that allows the use of this material in energy storage devices. Thus, the investigation of the frequency dependence of the ac conductivity proves a correlated barrier hopping (CBH) conduction mechanism to be dominant in the temperature ranges of 150-170 K; the two observed Jonscher's power law exponents, s 1 and s 2 between 180 K and 270 K correspond to the observed dispersions in the ac conductivity spectra in this temperature region, unlike in the temperature range of 250-320 K, the small polaron tunnel (NSPT) was considered the appropriate conduction model., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Despite an increase in screening colonoscopy, with the objective to decrease the incidence of colorectal cancer, a third of patients will present with an obstructing cancer. Malignant large bowel obstructions (MLBO) pose a challenging workup and treatment paradigm where an oncologic primary tumor resection must be balanced with relieving the obstruction, functional outcomes, palliation, and consideration for adjuvant therapy. A thorough work up with cross-sectional imaging and medical optimization should be attempted; however, patients may present in extremis and require emergent intervention. The onset of MLBO can be insidious, but result in electrolyte derangements, perforation, small bowel obstruction, hemorrhage, and ischemia. Self-expandable metallic stents have been used as palliation or as a bridge to surgery and have allowed for minimally invasive surgical options as well as a decrease in stoma rates. Patients with signs of colon ischemia or perforation require emergent surgery, which is associated with an increase in stoma formation, morbidity, mortality, and a decrease in overall survival., Competing Interests: Conflict of Interest None declared., (Thieme. All rights reserved.)

La 1-2 x Ba x Bi x FeO 3 (0.00 ≤ x ≤ 0.20) nanoparticles were prepared by the auto-combustion method using glycine as a combustion fuel. X-ray diffractometry (XRD) measurements confirmed the orthorhombic structure of the synthesized compounds with the Pnma space group as a principal majority phase and showed the presence of a very minor secondary phase when x > 0.1. The nanosize criterion of the prepared compounds was confirmed from the crystallite size values calculated using the Williamson-Hall formalism. The relaxation process has been studied by the frequency dependence of the imaginary parts of impedance and modulus ( Z '' and M '') which satisfied the Arrhenius law. Nyquist plots allowed us to obtain an adequate equivalent circuit involving the grains and grain boundary contributions. The activation energies calculated from Z '', M '' and the resistance of both contributions deduced from the Nyquist plots are found to be very similar. The conduction mechanism has been analyzed using the temperature dependence of the exponent Jonscher's power law parameter which confirms the NSPT conduction mechanism type for all compounds with an enhancement of the binding energy of the charge carrier ( W H ) with the substitution., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

This work involves the synthesis and study of physical properties of the La 0.8 Ca 0.1 Pb 0.1 Fe 0.975 Mg 0.025 O 3 compound, which has been characterized by various experimental techniques, such as X-ray diffraction, SEM and complex impedance spectroscopy. The structural study showed that the La 0.8 Ca 0.1 Pb 0.1 Fe 0.975 Mg 0.025 O 3 compound crystallized in the orthorhombic structure with the Pnma space group. The particle size and the surface morphology of this compound have been analysed using SEM. The particle size was found to be around 120 nm and we confirmed that one particle contains more than one crystallite. Importantly, the studied compound presented a giant dielectric permittivity ( ε ' of around 9 × 10 4 at high temperature and low frequencies). An equivalent electric circuit has been deduced from the Nyquist plots of the complex impedance parts ( Z '' vs. Z ') to correctly describe the electrical behavior of the La 0.8 Ca 0.1 Pb 0.1 Fe 0.975 Mg 0.025 O 3 compound. The chosen circuit consists of two cells mounted in series corresponding to the grain and grain boundary contributions. The electrode contribution has been detected from the frequency dependence of the imaginary part of modulus where the activation energy of each constitution has been calculated. The relaxation process and the electrical conductivity are attributed to the same type of charge carriers characterized by similar values of the activation energy determined from loss factor tangent (tg( δ )), the imaginary part of the permittivity and the modulus spectrum., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

The physical properties of the cubic and ferrimagnetic spinel ferrite LiFe 5 O 8 has made it an attractive material for electronic and medical applications. In this work, LiFe 5 O 8 nanosized crystallites were synthesized by a novel and eco-friendly sol-gel process, by using powder coconut water as a mediated reaction medium. The dried powders were heat-treated (HT) at temperatures between 400 and 1000 °C, and their structure, morphology, electrical and magnetic characteristics, cytotoxicity, and magnetic hyperthermia assays were performed. The heat treatment of the LiFe 5 O 8 powder tunes the crystallite sizes between 50 nm and 200 nm. When increasing the temperature of the HT, secondary phases start to form. The dielectric analysis revealed, at 300 K and 10 kHz, an increase of ε' (≈10 up to ≈14) with a tanδ almost constant (≈0.3) with the increase of the HT temperature. The cytotoxicity results reveal, for concentrations below 2.5 mg/mL, that all samples have a non-cytotoxicity property. The sample heat-treated at 1000 °C, which revealed hysteresis and magnetic saturation of 73 emu g -1 at 300 K, showed a heating profile adequate for magnetic hyperthermia applications, showing the potential for biomedical applications.

The hexaferrite Ba 1- x Sr x Fe 12 O 19 compounds with x = 0, 0.5 and 1 were synthesized by the autocombustion method. X-ray diffraction (XRD), Raman spectroscopy and transmission electron microscopy (TEM) were used for structural and morphological studies., Competing Interests: There are no conflicts of interest to declare., (This journal is © The Royal Society of Chemistry.)

(La 0.8 Ca 0.2 ) 1- x Bi x FeO 3 ( x = 0.00, 0.05, 0.10, 0.15 and 0.20) (LCBFO) multiferroic compounds have been prepared by the sol-gel method and calcined at 800 °C. X-ray diffraction results have shown that all samples crystallise in the orthorhombic structure with the Pnma space group. Electrical and dielectric characterizations of the synthesized materials have been performed using complex impedance spectroscopy techniques in the frequency range from 100 Hz to 1 MHz and in a temperature range from 170 to 300 K. The ac-conductivity spectra have been analysed using Jonscher's power law σ ( ω ) = σ dc + Aω s , where the power law exponent ( s ) increases with the temperature. The imaginary part of the complex impedance ( Z '') was found to be frequency dependent and shows relaxation peaks that move towards higher frequencies with the increase of the temperature. The relaxation activation energy deduced from the Z '' vs. frequency plots was similar to the conduction activation energy obtained from the conductivity. Hence, the relaxation process and the conduction mechanism may be attributed to the same type of charge carriers. The Nyquist plots ( Z '' vs. Z ') at different temperatures revealed the appearance of two semi-circular arcs corresponding to grain and grain boundary contributions., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

In this study, our central focus is to investigate the magnetocaloric characteristics of a La 1- x □ x MnO 3 ( x = 0.1, 0.2 and 0.3) series prepared by a sol-gel technique published in Prog. Mater. Sci. , 93 , 2018, 112-232. The crystallographic study revealed that our compounds crystallize in a rhombohedral structure with R 3̄ c . Ferromagnetic (FM) and paramagnetic (PM) characters were detected from the variation in magnetization as a function of magnetic fields at different temperatures. The second order transition was verified from the Arrott plots ( M 2 vs. ( μ 0 H / M )), where the slopes have a positive value. In order to verify the second order, we traced the variation of magnetization vs. temperature at different magnetic fields for x = 0.2. This revealed a ferromagnetic (FM)-paramagnetic (PM) transition when temperature increases. Relying on the indirect method while using the Maxwell formula, we determined the variation in the entropy (-Δ S M ) as a function of temperature for different magnetic fields for the three samples. We note that all the studied systems stand as good candidates for magnetic refrigeration with relative cooling power (RCP) values of around 131.4, 83.38 and 57.26 J kg -1 with magnetic fields below 2 T, respectively. Subsequently, the magnetocaloric effect was investigated by a phenomenological model for x = 0.2. The extracted data confirm that this phenomenological model is appropriate for the prediction of magnetocaloric properties. The study also demonstrated that this La 0.8 □ 0.2 MnO 3 system exhibits a universal behaviour., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Background: Controversial data exists in the current literature in regard to the use of neoadjuvant chemoradiation (nCRT) in patients with clinical T3N0 (cT3N0) rectal cancers, specifically based on location and relation to peritoneal reflection. We aimed to analyze the impact of nCRT on oncologic outcomes among cT3N0 rectal cancers, depending on the tumor height from anal verge (AV)., Methods: A retrospective analysis of patients with cT3N0 rectal cancers was included from a query of a prospectively maintained rectal cancer database from 1980 to 2016. Patients were divided into 3 groups based on the tumor height: low (1-5 cm from AV), mid (6-10 cm from AV), and upper (11-15 cm from AV). Patients were stratified by use of nCRT., Main Outcomes: 5-year overall survival (OS), disease-free survival (DFS), cancer-specific survival (CSS), and local recurrence (LR) using Kaplan-Meier curves., Results: Five hundred ninety-two patients were included. Overall, 364 (61.4%) patients received nCRT and 228 (38.6%) patients did not. There were 251 (43%) patients with low, 302 (51%) with mid, and 39 (7%) with upper rectal cancer. Patients with low and mid rectal cancers received nCRT more frequently than those with upper rectal cancers (68.5% and 61.2% vs 43.6%, p = 0.007). The 5-year OS was 78% and 63%, DFS-88% and 73%, LR-1% and 8% in nCRT followed by resection vs. surgery alone (p < 0.001). In regard to cancer location after nCRT compared with surgery alone, low and mid cancers had better OS, DFS, and CSS, compared with upper ones., Conclusion: nCRT prolongs survival among patients with rectal cancer below 10 cm from AV; however, it has no effect on 5-year oncologic survival of patients with upper rectal cancer located below peritoneal reflection.

The coupling between electric, magnetic and elastic features in multiferroic materials is an emerging field in materials science, with important applications on alternative solid-state cooling technologies, energy harvesting and sensors/actuators. In this direction, we developed a thorough investigation of a multiferroic composite, comprising magnetocaloric/magnetostrictive Gd[Formula: see text]Si[Formula: see text]Ge[Formula: see text] microparticles blended into a piezo- and pyroelectric poly(vinylidene) fluoride (PVDF) matrix. Using a simple solvent casting technique, the formation and stabilization of PVDF electroactive phases are improved when the filler content increases from 2 to 12 weight fraction (wt.%). This effect greatly contributes to the magnetoelectric (ME) coupling, with the ME coefficient [Formula: see text] increasing from 0.3 V/cm.Oe to 2.2 V/cm.Oe, by increasing the amount of magnetic material. In addition, magnetic measurements revealed that the ME-coupling has influenced the magnetocaloric effect via a contribution from the electroactive polymer and hence leading to a multicaloric effect. These results contribute to the development of multifunctional systems for novel technologies.

Anal cancer is a heterogeneous and rare disease process that accounts for ∼1.5% of all gastrointestinal tract malignancies. The perianal skin plays host to a variety of different premalignant and malignant lesions, all with variable histology, treatment options, and prognosis. Anal cancers in general are notorious for having a delayed or missed diagnosis leading to treatment delays and may have an impact on survival. This delay is in part due to the nonspecific symptomatology and also improper physical examination of the sensitive and anatomically complex perianal region and anal canal. This article examines the various types of perianal cancers and their precursor lesions and will explore treatment options as well as outcomes and prognosis.

Aims: Episodes of acute heart failure (AHF) unfavourably affect multiple organs, which may have an adverse impact on the outcomes. We investigated the prevalence and clinical consequences of abnormal liver function tests (LFTs) in AHF patients enrolled in the PROTECT study., Methods and Results: The LFTs comprised serial assessment of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and albumin at baseline and during follow-up (daily until discharge, on days 7 and 14). The prevalence of abnormal LFTs (above upper limit of normal for AST and ALT or below lower limit of normal for albumin) was: at baseline AST 20%, ALT 12%, albumin 40%; and at day 14: AST 15%, ALT 9%, albumin 26%. Abnormal LFTs at baseline were associated with a higher risk of in-hospital death with odds ratios [95% confidence interval (CI)] of 3.5 (1.7-7.3) for AST, 3.9 (1.8-8.4) for ALT, and 2.8 (1.3-5.9) for albumin (all P < 0.01). Abnormal baseline and discharge LFTs had an unfavourable impact on 180-day mortality with hazard ratios (95% CI) for baseline AST, ALT, and albumin of 1.3 (1.0-1.7), 1.1 (1.0-1.2), 1.4 (1.1-1.8), respectively, and 1.5 (1.1-2.0), 1.5 (1.0-2.2), and 1.6 (1.2-2.1), for discharge AST, ALT, albumin, respectively (all P < 0.05). Analysis of LFTs trajectories (calculated as changes in LFTs over time) revealed that increasing AST and ALT on day 3 as well as decreasing albumin on day 4 were independent prognosticators of 180-day outcome (all P < 0.05)., Conclusions: Abnormal LFTs are frequent in AHF at baseline and during hospital stay and predict worse outcomes. Whether this association is causal and what are the underlying mechanisms involved require further study., (© 2016 The Authors. European Journal of Heart Failure © 2016 European Society of Cardiology.)

Background: Both diuretic response and hemoconcentration are indicators of decongestion and have individually been found to predict rehospitalization after admission for acute heart failure (HF). This study examines the value of combining diuretic response and hemoconcentration to better predict patients at low risk for rehospitalization after admission for acute HF., Methods and Results: Diuretic response (defined as weight change per 40 mg of furosemide on day 4 after admission) and hemoconcentration (change in hemoglobin at discharge or day 7) were tested both individually and combined to predict the risk of HF and cardiovascular rehospitalization 60 days after hospitalization for acute HF. Analyses were performed in 1180 patients enrolled in the Placebo-Controlled Randomized Study of the Selective Adenosine Receptor Antagonist Rolofylline for Patients Hospitalized With Acute Decompensated Heart Failure and Volume Overload to Assess Treatment Effect on Congestion and Renal Function (PROTECT) trial and validated in 1776 patients enrolled in the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study With Tolvaptan (EVEREST) trial. Poor diuretic response was associated with low systolic blood pressure, high blood urea nitrogen, and history of coronary revascularization in both data sets (all P<0.05). Hemoconcentration was mainly associated with better renal function (P<0.05). Patients who displayed both favorable diuretic response and hemoconcentration had a markedly lower risk of rehospitalization for HF in PROTECT (multivariable HR, 0.41; 95% CI, 0.24 to 0.70; P<0.001) compared with all other patients. This finding was confirmed in EVEREST (multivariable HR, 0.52; 95% CI, 0.33 to 0.82; P=0.004) for patients with favorable diuretic response and hemoconcentration compared with all other patients., Conclusions: Combining 2 indicators of decongestion, hemoconcentration and diuretic response improves risk prediction for early rehospitalization after an admission for acute HF and may provide clinicians with an easily accessible tool to identify low-risk patients., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifiers: NCT00354458 and NCT00071331., (© 2016 American Heart Association, Inc.)

Aims: Our aim was to identify circulating microRNAs (miRNAs) associated with acute heart failure (AHF)., Methods and Results: Plasma miRNA profiling included 137 patients with AHF from 3 different cohorts, 20 with chronic heart failure (CHF), 8 with acute exacerbation of COPD, and 41 healthy controls. Levels of circulating miRNAs were measured using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Plasma levels of miRNAs in patients with AHF were decreased compared with CHF patients or healthy subjects, whereas no significant changes were observed between acute COPD patients and controls. Fifteen miRNAs found in the discovery phase to differ most significantly between healthy controls and patients with AHF were further investigated in an extended cohort of 100 AHF patients at admission and a separate cohort of 18 AHF patients at different time points. Out of these 15 miRNAs, 12 could be confirmed in an additional AHF validation cohort and 7 passed the Bonferroni correction threshold (miR-18a-5p, miR-26b-5p, miR-27a-3p, miR-30e-5p, miR-106a-5p, miR-199a-3p, and miR-652-3p, all P < 0.00005). A further drop in miRNA levels within 48 h after AHF admission was associated with an increased risk of 180-day mortality in a subset of the identified miRNAs., Conclusions: Declining levels of circulating miRNAs were associated with increasing acuity of heart failure. Early in-hospital decreasing miRNA levels were predictive for mortality in a subset of miRNAs in patients with AHF. The discovered miRNA panel may serve as a launch-pad for molecular pathway studies to identify new pharmacological targets and miRNA-based therapies., (© 2015 The Authors European Journal of Heart Failure © 2015 European Society of Cardiology.)

Aim: The clinical value of single biomarkers at single time-points to predict outcomes in patients with acute heart failure (AHF) is limited. We performed a multimarker, multi-time-point analysis of biomarkers for the prediction of post-discharge clinical outcomes in high-risk AHF patients., Methods and Results: A set of 48 circulating biomarkers were measured in the PROTECT trial which enrolled 2033 patients with AHF. Associations between baseline levels of biomarkers and outcomes (30-day all-cause mortality, 30-day death or rehospitalization for renal/cardiovascular causes and 180-day all-cause mortality) were evaluated. Prognostic accuracies of baseline, days 2 or 3, 7, and 14 biomarker measurements were estimated and compared utilizing a time-dependent area under the curve (AUC) analysis. Forty-four biomarkers were significantly associated with outcomes, but 42 had limited prognostic value (C-index < 0.70). However, multimarker models combining best-performing biomarkers from different clusters had a much stronger prognostic value. Combining blood urea nitrogen (BUN), chloride, interleukin (IL)-6, cTnI, sST-2 and VEGFR-1 into a clinical model yielded a 11% increase in C-index to 0.84 and 0.78 for 30-day and 180-day all-cause mortality, respectively, and cNRI of 0.86 95% CI [0.55-1.11] and 0.76 95% CI [0.57-0.87]. Prognostic gain was modest for the 30-day death/rehospitalization for cardiovascular or renal causes endpoint. Comparative time-dependent AUC analysis indicated that late measurements provided superior accuracy for the prediction of all-cause mortality over 180 days, with few exceptions including BUN and galectin-3. However, the predictive value of most biomarkers showed a diminishing pattern over time irrespective of moment of measurement., Conclusions: Multimarker models significantly improve risk prediction. Subsequent measurements, beyond admission, are needed for majority of biomarkers to maximize prognostic value over time, particularly in the long term., (© 2015 The Authors European Journal of Heart Failure © 2015 European Society of Cardiology.)

Purpose: Perianal Paget's disease is a rare intraepithelial adenocarcinoma of the perianal skin and the second most common localization of extramammary Paget's disease. This study was designed to evaluate long-term outcomes in patients with perianal Paget's disease., Methods: We identified patients who were treated for perianal Paget's disease between 1981 and 2013. Patient demographics, family history, associated malignancies, treatments, histopathological features, need for re-operations, and long-term outcomes were documented., Results: Our study cohort consisted of 15 male and 10 female patients with a median age of 67 (40-83) years. Four patients had concurrent anorectal adenocarcinoma (two anal canal, two rectal) when perianal Paget's disease was diagnosed. Index operations performed were wide local excision (14 patients), local excision (five patients), abdominoperineal resection (four patients), and radiotherapy (two patients). Five patients developed invasive carcinoma (three anal canal, one vulvar, one perianal squamous cell carcinoma) during a median follow-up time of 60 (3-299) months. Thirteen patients were re-operated. Fifteen patients had a reconstructive procedure following excision. Overall survival was similar between the patients who were treated with wide local excision and local excision regardless of surgical margin status at index excision (P = 0.75)., Conclusions: Since there is a risk for developing invasive carcinoma in the anal canal and perineum in patients with perianal Paget's disease, close follow-up is needed after R0 or R1 excision. Physicians should be aware of the risk of cancers associated with perianal Paget's disease and should rule out them during management.

Objective: In patients with diabetes mellitus, metformin treatment is associated with reduced mortality and attenuation of cardiovascular risk. As a subanalysis of the Glycometabolic Intervention as adjunct to Primary Coronary Intervention in ST Elevation Myocardial Infarction (GIPS-III) study, we evaluated whether metformin treatment in patients with ST-segment elevation myocardial infarction (STEMI) without diabetes improves the cardiovascular risk profile., Methods: A total of 379 patients, without known diabetes, presenting with STEMI were randomly allocated to receive metformin 500 mg twice daily or placebo for 4 months., Results: After 4 months, the cardiovascular risk profile of patients receiving metformin (n=172) was improved compared with placebo (n=174); glycated hemoglobin (5.83% (95% CI 5.79% to 5.87%) vs 5.89% (95% CI 5.85% to 5.92%); 40.2 mmol/mol (95% CI 39.8 to 40.6) vs 40.9 mmol/mol (40.4 to 41.2), p=0.049); total cholesterol (3.85 mmol/L (95% CI 3.73 to 3.97) vs 4.02 mmol/L (95% CI 3.90 to 4.14), p=0.045); low-density lipoprotein cholesterol (2.10 mmol/L (95% CI 1.99 to 2.20) vs 2.3 mmol/L (95% CI 2.20 to 2.40), p=0.007); body weight (83.8 kg (95% CI 83.0 to 84.7) vs 85.2 kg (95% CI 84.4 to 86.1), p=0.024); body mass index (26.8 kg/m(2) (95% CI 26.5 to 27.0) vs 27.2 kg/m(2) (95% CI 27.0 to 27.5), p=0.014). Levels of fasting glucose, postchallenge glucose, insulin, high-density lipoprotein cholesterol, and blood pressure were similar in both groups., Conclusions: Among patients with STEMI without diabetes, treatment with metformin for 4 months resulted in a modest improvement of the cardiovascular risk profile compared with placebo., Trial Register Number: NCT01217307.

We present the construction of a continuous, daily (09:00 UTC), station-based (Azores-Iceland) North Atlantic Oscillation (NAO) Index back to 1871 which is extended back to 1850 with additional daily mean data. The constructed index more than doubles the length of previously existing, widely available, daily NAO time series. The index is created using entirely observational sea-level pressure (SLP) data from Iceland and 73.5% of observational SLP data from the Azores - the remainder being filled in via reanalysis (Twentieth Century Reanalysis Project and European Mean Sea Level Pressure) SLP data. Icelandic data are taken from the Southwest Iceland pressure series. We construct and document a new Ponta Delgada SLP time series based on recently digitized and newly available data that extend back to 1872. The Ponta Delgada time series is created by splicing together several fractured records (from Ponta Delgada, Lajes, and Santa Maria) and filling in the major gaps (pre-1872, 1888-1905, and 1940-1941) and occasional days (145) with reanalysis data. Further homogeneity corrections are applied to the Azores record, and the daily (09:00 UTC) NAO index is then calculated. The resulting index, with its extended temporal length and daily resolution, is the first reconstruction of daily NAO back into the 19th Century and therefore is useful for researchers across multiple disciplines.

Many immune-based intestinal disorders, such as ulcerative colitis and Crohn's disease, as well as other illnesses, may have the intestines as an initial cause or aggravator in the development of diseases, even apparently not correlating directly to the intestine. Diabetes, obesity, multiple sclerosis, depression, and anxiety are examples of other illnesses discussed in the literature. In parallel, importance of the gut microbiota in intestinal homeostasis and immunologic conflict between tolerance towards commensal microorganisms and combat of pathogens is well known. Recent researches show that the immune system, when altered by the gut microbiota, influences the state in which these diseases are presented in the patient directly and indirectly. At the present moment, a considerable number of investigations about this subject have been performed and published. However, due to difficulties on correlating information, several speculations and hypotheses are generated. Thus, the present review aims at bringing together how these interactions work-gut microbiota, immune system, and their influence in the neuroimmune system.

Rectovaginal fistula is a disastrous complication of Crohn's disease (CD) that is exceedingly difficult to treat. It is a disabling condition that negatively impacts a women's quality of life. Successful management is possible only after accurate and complete assessment of the entire gastrointestinal tract has been performed. Current treatment algorithms range from observation to medical management to the need for surgical intervention. A wide variety of success rates have been reported for all management options. The choice of surgical repair methods depends on various fistula and patient characteristics. Before treatment is undertaken, establishing reasonable goals and expectations of therapy is essential for both the patient and surgeon. This article aims to highlight the various surgical techniques and their outcomes for repair of CD associated rectovaginal fistula.

Aim: Diminished diuretic response is common in patients with acute heart failure, although a clinically useful definition is lacking. Our aim was to investigate a practical, workable metric for diuretic response, examine associated patient characteristics and relationships with outcome., Methods and Results: We examined diuretic response (defined as Δ weight kg/40 mg furosemide) in 1745 hospitalized acute heart failure patients from the PROTECT trial. Day 4 response was used to allow maximum differentiation in responsiveness and tailoring of diuretic doses to clinical response, following sensitivity analyses. We investigated predictors of diuretic response and relationships with outcome. The median diuretic response was -0.38 (-0.80 to -0.13) kg/40 mg furosemide. Poor diuretic response was independently associated with low systolic blood pressure, high blood urea nitrogen, diabetes, and atherosclerotic disease (all P < 0.05). Worse diuretic response independently predicted 180-day mortality (HR: 1.42; 95% CI: 1.11-1.81, P = 0.005), 60-day death or renal or cardiovascular rehospitalization (HR: 1.34; 95% CI: 1.14-1.59, P < 0.001) and 60-day HF rehospitalization (HR: 1.57; 95% CI: 1.24-2.01, P < 0.001) in multivariable models. The proposed metric-weight loss indexed to diuretic dose-better captures a dose-response relationship. Model diagnostics showed diuretic response provided essentially the same or slightly better prognostic information compared with its individual components (weight loss and diuretic dose) in this population, while providing a less biased, more easily interpreted signal., Conclusions: Worse diuretic response was associated with more advanced heart failure, renal impairment, diabetes, atherosclerotic disease and in-hospital worsening heart failure, and predicts mortality and heart failure rehospitalization in this post hoc, hypothesis-generating study., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.)

The binding protein (BiP) has been demonstrated to participate in innate immunity and attenuate endoplasmic reticulum- and osmotic stress-induced cell death. Here, we employed transgenic plants with manipulated levels of BiP to assess whether BiP also controlled developmental and hypersensitive programmed cell death (PCD). Under normal conditions, the BiP-induced transcriptome revealed a robust down-regulation of developmental PCD genes and an up-regulation of the genes involved in hypersensitive PCD triggered by nonhost-pathogen interactions. Accordingly, the BiP-overexpressing line displayed delayed leaf senescence under normal conditions and accelerated hypersensitive response triggered by Pseudomonas syringae pv tomato in soybean (Glycine max) and tobacco (Nicotiana tabacum), as monitored by measuring hallmarks of PCD in plants. The BiP-mediated delay of leaf senescence correlated with the attenuation of N-rich protein (NRP)-mediated cell death signaling and the inhibition of the senescence-associated activation of the unfolded protein response (UPR). By contrast, under biological activation of salicylic acid (SA) signaling and hypersensitive PCD, BiP overexpression further induced NRP-mediated cell death signaling and antagonistically inhibited the UPR. Thus, the SA-mediated induction of NRP cell death signaling occurs via a pathway distinct from UPR. Our data indicate that during the hypersensitive PCD, BiP positively regulates the NRP cell death signaling through a yet undefined mechanism that is activated by SA signaling and related to ER functioning. By contrast, BiP's negative regulation of leaf senescence may be linked to its capacity to attenuate the UPR activation and NRP cell death signaling. Therefore, BiP can function either as a negative or positive modulator of PCD events.

Aims: Chronic kidney disease (CKD) and worsening renal function (WRF) have been associated with poor outcome in heart failure (HF)., Methods and Results: Articles were identified by literature search of MEDLINE (from inception to 1 July 2012) and Cochrane. We included studies on HF patients and mortality risk with CKD and/or WRF. In a secondary analysis, we selected studies investigating predictors of WRF. We retrieved 57 studies (1,076,104 patients) that investigated CKD and 28 studies (49,890 patients) that investigated WRF. The prevalence of CKD was 32% and associated with all-cause mortality: odds ratio (OR) 2.34, 95% confidence interval (CI) 2.20-2.50, P < 0.001). Worsening renal function was present in 23% and associated with unfavourable outcome (OR 1.81, 95% CI 1.55-2.12, P < 0.001). In multivariate analysis, moderate renal impairment: hazard ratio (HR) 1.59, 95% CI 1.49-1.69, P < 0.001, severe renal impairment, HR 2.17, 95% CI 1.95-2.40, P < 0.001, and WRF, HR 1.95, 95% CI 1.45-2.62, P < 0.001 were all independent predictors of mortality. Across studies, baseline CKD, history of hypertension and diabetes, age, and diuretic use were significant predictors for the occurrence of WRF., Conclusion: Across all subgroups of patients with HF, CKD, and WRF are prevalent and associated with a strongly increased mortality risk, especially CKD. Specific conditions may predict the occurrence of WRF and thereby poor prognosis.

Aims: The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula estimates glomerular filtration rate (GFR) better than the simplified Modification of Diet in Renal Disease (sMDRD) formula in numerous populations. It has not previously been validated in heart failure patients., Methods and Results: The GFR was measured in 120 patients with chronic systolic heart failure (CHF) using [(125)I]iothalamate clearance (GFR(IOTH)) and estimated using the sMDRD and CKD-EPI equations. Accuracy, bias, and prognostic performance were compared. Cockcroft-Gault, CKD-EPI serum cystatin C, and CKD-EPI creatinine-serum cystatin C equations were compared in secondary analyses. Mean age was 59 ± 12 years, 80% were male. Mean LVEF was 29 ± 10%. Mean GFR(IOTH) was 74 ± 27 mL/min/1.73 m(2), and mean estimated GFR was 66 ± 23 mL/min/1.73 m(2) (CKD-EPI) and 63 ± 21 mL/min/1.73m(2) (sMDRD). CKD-EPI showed less bias than sMDRD (-8 ± 15 vs. -11 ± 16 mL/min/1.73 m(2), P < 0.001). Both equations underestimate at higher and overestimate at lower GFR(IOTH). Eleven patients (9%) were accurately reclassified into lower CKD classes with CKD-EPI. Cockcroft-Gault showed lower bias (-3 ± 16 mL/min/1.73 m(2)) but worse precision and accuracy. Cystatin C-based estimation showed the lowest bias (-3 ± 14 mL/min/1.73 m(2)) and the best precision and accuracy. Prognostic value did not differ between all GFR estimates, Conclusion: The CKD-EPI equation more accurately estimates measured GFR than the sMDRD equation in CHF patients, with less bias and greater accuracy and precision. The prognostic power of all GFR assessments was equivalent. Based on better performance and equal risk prediction, we believe the CKI-EPI equation should be the preferred creatinine-based GFR estimation method in heart failure patients, particularly those with preserved or moderately impaired renal function., (First published online by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. © The Author 2013.)

Background: Traumatic cloaca due to severe obstetric injury is a disabling condition that results in debilitating fecal incontinence, sexual dysfunction, and psychosocial distress for the patients, and poses a complex and challenging clinical situation for the surgeon. The aim of this study is to describe our technique and functional outcomes for the surgical repair of traumatic cloacal deformities., Methods: Between 2000 and 2010, four women with traumatic cloacal deformities related to obstetric injury underwent repair by a single surgeon. In all patients, a systematic layered repair of the anovaginal structures was performed, including internal and external sphincteroplasties, without the implementation of tissue flaps or fecal diversion. Anorectal function before and after surgery as well as wound healing was evaluated. The patients presented 4.8 years after the obstetric injury. Mean preoperative Fecal Incontinence Severity Index was 34. All patients had complete disruption of the perineum, anal canal, distal vagina, and rectum, with a mean external sphincter defect of 151 degrees., Results: Postoperatively, there were no wound-related complications and complete healing occurred by the fourth week. Median long-term follow-up was 4.5 years. At long-term follow-up, mean postoperative Fecal Incontinence Severity Index score was zero and all patients reported complete absence of dyspareunia., Conclusions: A layered surgical repair of cloacal deformities after severe obstetrical injury is associated with excellent functional outcomes and cosmetic results. The need for fecal diversion or complex surgical flaps for wound closure is obviated in this small series., (© Springer-Verlag 2011)

Objective: The aim of this study was to examine the associations between coping and adjustment to chronic pain in a sample of patients from Portugal and to discuss the findings with respect to published findings from two studies using patients from the United States., Design: Two brief measures of pain coping were translated and administered with measures of physical and psychological functioning to a sample of Portuguese patients. Analyses examined the associations among the study variables and compared the results with published data from two patient samples from the United States., Participants: One hundred seventeen individuals with chronic musculoskeletal pain., Outcome Measures: Portuguese translations of brief versions of the Coping Strategies Questionnaire and Chronic Pain Coping Inventory and criterion measures of pain intensity, pain interference, and depression., Results: Statistically significant positive associations were found between measures of patient dysfunction and catastrophizing, praying/hoping, guarding, asking for assistance, and support seeking; and negative associations were found between the criterion measures and ignoring sensations, coping self-statements, and increasing behavioral activities. Mean differences between the Portuguese and US samples in the coping scales were found for nine of the 15 coping scales., Conclusions: The results support the reliability and validity of the translated Coping Strategies Questionnaire and Chronic Pain Coping Inventory and also indicate a number of similarities, but also some interesting differences, in the findings from the Portuguese vs US samples, suggesting that there may be cultural differences in how people cope with pain., (Wiley Periodicals, Inc.)

The ER-resident molecular chaperone BiP (binding protein) was overexpressed in soybean. When plants growing in soil were exposed to drought (by reducing or completely withholding watering) the wild-type lines showed a large decrease in leaf water potential and leaf wilting, but the leaves in the transgenic lines did not wilt and exhibited only a small decrease in water potential. During exposure to drought the stomata of the transgenic lines did not close as much as in the wild type, and the rates of photosynthesis and transpiration became less inhibited than in the wild type. These parameters of drought resistance in the BiP overexpressing lines were not associated with a higher level of the osmolytes proline, sucrose, and glucose. It was also not associated with the typical drought-induced increase in root dry weight. Rather, at the end of the drought period, the BiP overexpressing lines had a lower level of the osmolytes and root weight than the wild type. The mRNA abundance of several typical drought-induced genes [NAC2, a seed maturation protein (SMP), a glutathione-S-transferase (GST), antiquitin, and protein disulphide isomerase 3 (PDI-3)] increased in the drought-stressed wild-type plants. Compared with the wild type, the increase in mRNA abundance of these genes was less (in some genes much less) in the BiP overexpressing lines that were exposed to drought. The effect of drought on leaf senescence was investigated in soybean and tobacco. It had previously been reported that tobacco BiP overexpression or repression reduced or accentuated the effects of drought. BiP overexpressing tobacco and soybean showed delayed leaf senescence during drought. BiP antisense tobacco plants, conversely, showed advanced leaf senescence. It is concluded that BiP overexpression confers resistance to drought, through an as yet unknown mechanism that is related to ER functioning. The delay in leaf senescence by BiP overexpression might relate to the absence of the response to drought.

NRPs (N-rich proteins) were identified as targets of a novel adaptive pathway that integrates endoplasmic reticulum (ER) and osmotic stress signals based on coordinate regulation and synergistic up-regulation by tunicamycin and polyethylene glycol treatments. This integrated pathway diverges from the molecular chaperone-inducing branch of the unfolded protein response (UPR) in several ways. While UPR-specific targets were inversely regulated by ER and osmotic stresses, NRPs required both signals for full activation. Furthermore, BiP (binding protein) overexpression in soybean prevented activation of the UPR by ER stress inducers, but did not affect activation of NRPs. We also found that this integrated pathway transduces a PCD signal generated by ER and osmotic stresses that result in the appearance of markers associated with leaf senescence. Overexpression of NRPs in soybean protoplasts induced caspase-3-like activity and promoted extensive DNA fragmentation. Furthermore, transient expression of NRPs in planta caused leaf yellowing, chlorophyll loss, malondialdehyde production, ethylene evolution, and induction of the senescence marker gene CP1. This phenotype was alleviated by the cytokinin zeatin, a potent senescence inhibitor. Collectively, these results indicate that ER stress induces leaf senescence through activation of plant-specific NRPs via a novel branch of the ER stress response.

The title complex, [Cu(C(12)H(9)N(2)O)(C(2)H(3)O(2))(C(12)H(10)N(2)O)], is a neutral Cu(II) complex with a primary N(3)O(2) coordination sphere. The Cu centre coordinates to both a deprotonated and a neutral molecule of N-phenylpyridine-2-carboxamide and also to an acetate anion. The coordination around the metal centre is asymmetric, the deprotonated ligand providing two N donor atoms [Cu-N = 1.995 (2) and 2.013 (2) Angstrom] and the neutral ligand providing one N and one O donor atom to the coordination environment [Cu-N = 2.042 (2) Angstrom and Cu-O = 2.2557 (19) Angstrom], the fifth donor being an O atom of the acetate ion [Cu-O = 1.9534 (19) Angstrom]. The remaining O atom from the acetate ion can be considered as a weak donor atom [Cu-O = 2.789 (2) Angstrom], conferring to the Cu complex an asymmetric octahedral geometry. The crystal structure is stabilized by intermolecular N-H...O, C-H...O and C-H...pi interactions.