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Beyond the many structural obstacles to obtaining abortion care in the United States, abortion stigma is a forceful impediment to accessing timely services and an injurious feature of the experience for some people who have abortions (Sorhaindo & Lavelanet, 2022). This study utilized a qualitative methodology to explore the experiences of 830 abortion fund applicants in the Rocky Mountain Region to better understand the unique barriers they face in accessing care, the role that stigma plays in influencing applications for abortion fund support, and inform strategies to expand support infrastructure for those facing isolation and hostility in their pursuit of care. For the applicants in this study, stigma was frequently cited as an impetus for seeking abortion fund support and a burdensome aspect of the experience itself. Stigma—whether internalized, perceived, enacted, or structural—prevented many applicants from seeking material or emotional support from their social networks and spurred the dissolution of interpersonal relationships—with far-reaching emotional and material consequences. The results suggest that abortion funds go far beyond merely providing material support, also acting as an antidote to the harms associated with abortion stigma by promoting feelings of interconnectedness and mutuality among applicants. While accounts of stigma were pervasive in the applications, so, too, were the myriad strategies of resistance that applicants called upon to challenge stigmatizing narratives and position their choice to have an abortion as both moral and necessary.

We report a case of simultaneous transcatheter aortic valve replacement and endovascular aneurysm repair. Our aim was to advocate the role of local and regional anesthesia as a key contributor in maintaining hemodynamic stability and avoiding abrupt blood pressure change. Endovascular combined procedures are gaining popularity for their numerous advantages. Nevertheless, they carry significant risks for their hemodynamic implications. It is imperative to acknowledge the modifications occurring after each correction and act accordingly. Different anesthesia approaches can dramatically influence hemodynamics; among all, we found local and regional anesthesia would better serve this objective.

Background and aimsWith the advent and implementation of high-sensitivity cardiac troponin assays, differentiation of patients with distinct types of myocardial injuries, including acute thrombotic myocardial infarction (TMI), acute non-thrombotic myocardial injury (nTMi), and chronic coronary atherosclerotic disease (cCAD), is of pressing clinical importance. Thermal liquid biopsy (TLB) emerges as a valuable diagnostic tool, relying on identifying thermally induced conformational changes of biomolecules in blood plasma. While TLB has proven useful in detecting and monitoring several cancers and autoimmune diseases, its application in cardiovascular diseases remains unexplored. In this proof-of-concept study, we sought to determine and characterize TLB profiles in patients with TMI, nTMi, and cCAD at multiple acute-phase time points (T 0 h, T 2 h, T 4 h, T 24 h, T 48 h) as well as a follow-up time point (Tfu) when the patient was in a stable state.MethodsTLB profiles were collected for 115 patients (60 with TMI, 35 with nTMi, and 20 with cCAD) who underwent coronary angiography at the event presentation and had subsequent follow-up. Medical history, physical, electrocardiographic, histological, biochemical, and angiographic data were gathered through medical records, standardized patient interviews, and core laboratory measurements.ResultsDistinctive signatures were noted in the median TLB profiles across the three patient types. TLB profiles for TMI and nTMi patients exhibited gradual changes from T0 to Tfu, with significant differences during the acute and quiescent phases. During the quiescent phase, all three patient types demonstrated similar TLB signatures. An unsupervised clustering analysis revealed a unique TLB signature for the patients with TMI. TLB metrics generated from specific features of TLB profiles were tested for differences between patient groups. The first moment temperature (TFM) metric distinguished all three groups at time of presentation (T0). In addition, 13 other TLB-derived metrics were shown to have distinct distributions between patients with TMI and those with cCAD.ConclusionOur findings demonstrated the use of TLB as a sensitive and data-rich technique to be explored in cardiovascular diseases, thus providing valuable insight into acute myocardial injury events.

De los cuatro enclaves que integraron el proyecto colonizador español de la costa patagónica, solo el Fuerte San José y el Puesto de la Fuente -Península Valdés, provincia de Chubut- fueron destruidos y abandonados como consecuencia de un supuesto ataque indígena en 1810. Hasta el día de hoy, las causas de este evento permanecen imprecisas y, a lo largo del tiempo, se han sugerido distintas explicaciones. En base a los avances realizados en los últimos años, el objetivo del presente trabajo es discutir este último malón en términos de su complejidad a partir de la confrontación crítica de distintas fuentes escritas primarias, presentando evidencia inédita hasta el momento. Los resultados generados permiten formular la hipótesis en la que pobladores del fuerte tuvieron algún grado de participación en el ataque. La intervención directa de estos últimos podría tener implicancias en términos del correlato arqueológico y bioarqueológico de la confrontación.

Melanoma is the fifth most common cancer in the United States and the deadliest of all skin cancers. Even with recent advancements in treatment, there is still a 13% two-year recurrence rate, with approximately 30% of recurrences being distant metastases. Identifying patients at high risk for recurrence or advanced disease is critical for optimal clinical decision-making. Currently, there is substantial variability in the selection of screening tests and imaging, with most modalities characterized by relatively low accuracy. In the current study, we built upon a preliminary examination of differential scanning calorimetry (DSC) in the melanoma setting to examine its utility for diagnostic and prognostic assessment. Using regression analysis, we found that selected DSC profile (thermogram) parameters were useful for differentiation between melanoma patients and healthy controls, with more complex models distinguishing melanoma patients with no evidence of disease from patients with active disease. Thermogram features contributing to the third principal component (PC3) were useful for differentiation between controls and melanoma patients, and Cox proportional hazards regression analysis indicated that PC3 was useful for predicting the overall survival of active melanoma patients. With the further development and optimization of the classification method, DSC could complement current diagnostic strategies to improve screening, diagnosis, and prognosis of melanoma patients.

Both viral infection and vaccination affect the antibody repertoire of a person. Here, we demonstrate that the analysis of serum antibodies generates information not only on the virus type that caused the infection but also on the specific virus variant. We developed a rapid multiplex assay providing a fingerprint of serum antibodies against five different SARS-CoV-2 variants based on a microarray of virus antigens immobilized on the surface of a label-free reflectometric biosensor. We analyzed serum from the plasma of convalescent subjects and vaccinated volunteers and extracted individual antibody profiles of both total immunoglobulin Ig and IgA fractions. We found that Ig level profiles were strongly correlated with the specific variant of infection or vaccination and that vaccinated subjects displayed a larger quantity of total Ig and a lower fraction of IgA relative to the population of convalescent unvaccinated subjects.

BackgroundProper evaluation of therapeutic responses in Chagas disease is hampered by the prolonged persistence of antibodies to Trypanosoma cruzi measured by conventional serological tests and by the lack of sensitivity of parasitological tests. Previous studies indicated that tGPI-mucins, an α-Gal (α-d-Galp(1→3)-β-d-Galp(1→4)-d-GlcNAc)-rich fraction obtained from T. cruzi trypomastigotes surface coat, elicit a strong and protective antibody response in infected individuals, which disappears soon after successful treatment. The cost and technical difficulties associated with tGPI-mucins preparation, however, preclude its routine implementation in clinical settings.Methods/principle findingsWe herein developed a neoglycoprotein consisting of a BSA scaffold decorated with several units of a synthetic α-Gal antigenic surrogate (α-d-Galp(1→3)-β-d-Galp(1→4)-β-d-Glcp). Serological responses to this reagent, termed NGP-Tri, were monitored by means of an in-house enzyme-linked immunosorbent assay (α-Gal-ELISA) in a cohort of 82 T. cruzi-infected and Benznidazole- or Nifurtimox-treated children (3 days to 16 years-old). This cohort was split into 3 groups based on the age of patients at the time of treatment initiation: Group 1 comprised 24 babies (3 days to 5 months-old; median = 26 days-old), Group 2 comprised 31 children (7 months to 3 years-old; median = 1.0-year-old) and Group 3 comprised 26 patients (3 to 16 years-old; median = 8.4 years-old). A second, control cohort (Group 4) included 39 non-infected infants (3 days to 5 months-old; median = 31 days-old) born to T. cruzi-infected mothers. Despite its suboptimal seroprevalence (58.4%), α-Gal-ELISA yielded shorter median time values of negativization (23 months [IC 95% 7 to 36 months] vs 60 months [IC 95% 15 to 83 months]; p = 0.0016) and higher rate of patient negative seroconversion (89.2% vs 43.2%, p < 0.005) as compared to conventional serological methods. The same effect was verified for every Group, when analyzed separately. Most remarkably, 14 out of 24 (58.3%) patients from Group 3 achieved negative seroconversion for α-Gal-ELISA while none of them were able to negativize for conventional serology. Detailed analysis of patients showing unconventional serological responses suggested that, in addition to providing a novel tool to shorten follow-up periods after chemotherapy, the α-Gal-ELISA may assist in other diagnostic needs in pediatric Chagas disease.Conclusions/significanceThe tools evaluated here provide the cornerstone for the development of an efficacious, reliable, and straightforward post-therapeutic marker for pediatric Chagas disease.

Digitalization techniques, such as photogrammetry (PG), are attracting the interest of experts in the cultural heritage field, as they enable the creation of three-dimensional virtual replicas of historical artifacts with 2D digital images. Indeed, PG allows for acquiring data regarding the overall appearance of an artifact, its geometry, and its texture. Furthermore, among several image-based techniques exploited for the conservation of works of art, multispectral imaging (MSI) finds great application in the study of the materials of historical items, taking advantage of the different responses of materials when exposed to specific wavelengths. Despite their great usefulness, PG and MSI are often used as separate tools. Integrating radiometric and geometrical data can notably expand the information carried by a 3D model. Therefore, this paper presents a novel research methodology that enables the acquisition of multispectral 3D models, combining the outcomes of PG and MSI (Visible (VIS), Ultraviolet-induced Visible Luminescence (UVL), Ultraviolet-Reflected (UVR), and Ultraviolet-Reflected False Color (UVR-FC) imaging) in a single coordinate system, using an affordable tunable set-up and open-source software. The approach has been employed for the study of two wooden artifacts from the Museo Egizio di Torino to investigate the materials present on the surface and provide information that could support the design of suitable conservation treatments.

BackgroundTrypanosoma cruzi, the agent of Chagas disease, displays a highly structured population, with multiple strains that can be grouped into 6-7 evolutionary lineages showing variable eco-epidemiological traits and likely also distinct disease-associated features. Previous works have shown that antibody responses to 'isoforms' of the polymorphic parasite antigen TSSA enable robust and sensitive identification of the infecting strain with near lineage-level resolution. To optimize the serotyping performance of this molecule, we herein used a combination of immunosignaturing approaches based on peptide microarrays and serum samples from Chagas disease patients to establish a deep linear B-cell epitope profiling of TSSA.Methods/principle findingsOur assays revealed variations in the seroprevalence of TSSA isoforms among Chagas disease populations from different settings, hence strongly supporting the differential distribution of parasite lineages in domestic cycles across the Americas. Alanine scanning mutagenesis and the use of peptides of different lengths allowed us to identify key residues involved in antibody pairing and the presence of three discrete B-cell linear epitopes in TSSAII, the isoform with highest seroprevalence in human infections. Comprehensive screening of parasite genomic repositories led to the discovery of 9 novel T. cruzi TSSA variants and one TSSA sequence from the phylogenetically related bat parasite T. cruzi marinkellei. Further residue permutation analyses enabled the identification of diagnostically relevant or non-relevant substitutions among TSSA natural polymorphisms. Interestingly, T. cruzi marinkellei TSSA displayed specific serorecognition by one chronic Chagas disease patient from Colombia, which warrant further investigations on the diagnostic impact of such atypical TSSA.Conclusions/significanceOverall, our findings shed new light into TSSA evolution, epitope landscape and modes of recognition by Chagas disease patients; and have practical implications for the design and/or evaluation of T. cruzi serotyping strategies.

The research in the field of optical biosensors is continuously expanding, thanks both to the introduction of brand new technologies and the ingenious use of established methods. A new awareness on the potential societal impact of this research has arisen as a consequence of the Covid-19 pandemic. The availability of a new generation of analytical tools enabling a more accurate understanding of bio-molecular processes or the development of distributed diagnostic devices with improved performance is now in greater demand and more clearly envisioned, but not yet achieved. In this review, we focus on emerging innovation opportunities conveyed by label-free optical biosensors. We review the most recent innovations in label-free optical biosensor technology in consideration of their competitive potential in selected application areas. The operational simplicity implicit to label-free detection can be exploited in novel rapid and compact devices for distributed diagnostic applications. The adaptability to any molecular recognition or conformational process facilitates the integration of DNA nanostructures carrying novel functions. The high sensitivity to nanoscale objects stimulates the development of ultrasensitive systems down to digital detection of single molecular binding events enhanced by nanoparticles and direct enumeration of bio-nanoparticles like viruses.

“Desafíos Educativos Reales” (DER) es una asignatura de la Licenciatura en Ciencias de la Educación de una universidad de Buenos Aires, Argentina. Apoyándose en el Aprendizaje Basado en Proyectos, el Pensamiento de Diseño, el Aprendizaje Cooperativo y la Metacognición como pilares pedagógico-didácticos, la asignatura propone que los estudiantes investiguen una problemática educativa auténtica actual, y luego diseñen y comuniquen una propuesta innovadora y viable para resolverla. En 2020, el confinamiento social obligatorio por la pandemia por COVID-19 nos presentó el desafío de migrar el dictado de DER a la modalidad virtual. En este artículo relatamos y reflexionamos sobre esta experiencia, tomando como fuentes de información las producciones de los estudiantes y diversos materiales que utilizamos para la enseñanza. Describimos las principales transformaciones necesarias en la virtualidad, analizando sus oportunidades y limitaciones. Nuestro análisis muestra que la utilización intensiva de diversidad de herramientas digitales potenció aspectos clave de la asignatura, como el acompañamiento docente y el trabajo colaborativo de los estudiantes, y favoreció la disponibilidad de evidencias para la metacognición. También promovió el diseño de soluciones que, adaptadas al contexto remoto, incorporaron lo digital como elemento central. En contrapartida, la imposibilidad de realizar trabajo de campo presencial fue la mayor limitación. Considerando que, más allá de la emergencia sanitaria, la educación virtual y/o híbrida se ha instalado como alternativa educativa, esta experiencia invita a repensar las prácticas de enseñanza universitaria, atendiendo al valor de la tecnología para enriquecer la educación remota, e identificando aquello irremplazable que aporta la presencialidad.

School: The fragile construction of self in remote educational mediation. Nursey school and kindergarten in Sicily ------- Abstract --- The situation experienced during the period of Covid-19 was characterized by the zeroing of sociality on the one hand and the need to rebuild one's identity on the other. For the youngest children, already struggling to manage their emotions, it was a complex process that involved fatigue in the effort. Some questions emerge: how did the children manage their own space, often shared with all the other family members? What did this period of lockdown mean for their social and emotional growth? Ethnographic research is still ongoing, full of answers but even more of questions Keywords: Covid-19, dad, technologies in teaching, school community

Abstract Background Chemoprevention of colorectal neoplasia with aspirin and statins is under-investigated in Black patients. Since Black patients suffer disproportionately from colon cancer incidence and mortality compared to other populations, we investigated the utility of aspirin and statin in reducing advanced adenomatous polyp (AAP) risk in Black patients. Methods We carried out a retrospective cohort study of screening colonoscopies performed at a large urban academic center from 1/1/2011 through 12/31/2019. We analyzed self-identified Black patients with > 1 colonoscopy and no personal history of either inflammatory bowel disease or colon cancer syndromes. Our primary endpoint was first AAP development after index colonoscopy among Black patients taking both aspirin and a statin compared to those taking one or neither medication. We used multivariate logistic regression modeling to investigate our outcomes. Results We found data on chemoprophylaxis use in 560 patients. The mean observation period between index colonoscopy and AAP identification was 4 years. AAP developed in 106/560 (19%) of our cohort. We found no difference in AAP risk among Black patients taking both chemoprevention medications compared to partial or no chemoprophylaxis (20% vs 18% respectively, p = 0.49). This finding remained after adjusting for age, body mass index, and tobacco use (odds ratio 1.04, 95% CI 0.65–1.67; p = 0.87). Conclusions Short-term aspirin-statin chemoprevention did not reduce the risk of AAP development in our cohort of Black patients. Larger and long-term prospective investigations are needed to investigate the utility of chemoprophylaxis in this population. Trial Registration: Not applicable.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes the coronavirus disease 2019 (COVID-19), ranging from asymptomatic conditions to severe/fatal lung injury and multi-organ failure. Growing evidence shows that the nasopharyngeal microbiota composition may predict the severity of respiratory infections and may play a role in the protection from viral entry and the regulation of the immune response to the infection. In the present study, we have characterized the nasopharyngeal bacterial microbiota (BNM) composition and have performed factor analysis in a group of 54 asymptomatic/paucisymptomatic subjects who tested positive for nasopharyngeal swab SARS-CoV-2 RNA and/or showed anti-RBD-IgG positive serology at the enrolment. We investigated whether BNM was associated with SARS-CoV-2 RNA positivity and serum anti-RBD-IgG antibody development/maintenance 20–28 weeks after the enrolment. Shannon’s entropy α-diversity index [odds ratio (OR) = 5.75, p = 0.0107] and the BNM Factor1 (OR = 2.64, p = 0.0370) were positively associated with serum anti-RBD-IgG antibody maintenance. The present results suggest that BNM composition may influence the immunological memory against SARS-CoV-2 infections. To the best of our knowledge, this is the first study investigating the link between BNM and specific IgG antibody maintenance. Further studies are needed to unveil the mechanisms through which the BNM influences the adaptive immune response against viral infections.

Introducción: la información sobre las causas de muerte es de gran importancia tanto para los países como para las instituciones sanitarias, en la medida en que contribuye a la evaluación y el seguimiento del estado de salud de la población y a la planificación de intervenciones sanitarias. El objetivo del estudio fue evaluar la proporción de causas de muerte mal definidas e imprecisas y su relación con el día de la semana y período lectivo de médicos residentes en el Hospital Italiano de Buenos Aires (HIBA) durante 2020. Métodos: se realizó un estudio analítico de corte transversal a partir de certificados médicos de defunción de pacientes fallecidos en el ámbito intrahospitalario, evaluando las causas de muerte mal definidas (términos médicos que no aportan información desde el punto de vista clínico y epidemiológico) y las imprecisas (no resultan lo suficientemente específicas como para identificar entidades nosológicas que permitan establecer acciones de prevención y control). Resultados: se analizaron 1030 certificados de defunción, con una proporción de certificados con causa básica de muerte mal definida del 2,3% (n =24), mientras que en el 17,4% (n =180) fue imprecisa. No se hallaron diferencias entre la proporción de causas básicas mal definidas y las imprecisas según el día de la semana o período lectivo. Al extender el análisis a todas las causas (básicas, mediatas e inmediatas), la proporción de causas mal definidas fue del 1,6% (n =40) y la de imprecisas del 51% (n =1212). Conclusiones: los resultados definen al HIBA como un centro de mediana calidad estadística en el registro de causas de muerte. Se concluye que es necesario mejorarla, para lo que resulta de interés la creación de un plan de capacitación y entrenamiento de los médicos en el grado y el posgrado.

Abstract Background Biliary decompression can reduce symptoms and improve quality of life in patients with malignant biliary obstruction. Endoscopically placed stents have become the standard of care for biliary drainage with the aim of improving hepatic function, relieving jaundice, and reducing adverse effects of obstruction. The purpose of this study was to evaluate the performance characteristics of a newly-designed, uncovered metal biliary stent for the palliation of malignant biliary obstruction. Methods This post-market, prospective study included patients with biliary obstruction due to a malignant neoplasm treated with a single-type, commercially available uncovered self-expanding metal stent (SEMS). Stents were placed as clinically indicated for palliation of jaundice and to potentially facilitate neo-adjuvant chemotherapy. The main outcome measure was freedom from recurrent biliary obstruction (within the stent) requiring re-intervention within 1, 3, and 6 months of stent insertion. Secondary outcome measures included device-related adverse events and technical success of stent deployment. Results SEMS were placed in 113 patients (73 men; mean age, 69); a single stent was inserted in 106 patients, and 2 stents were placed in 7 patients. Forty-eight patients survived and/or completed the 6 month study protocol. Freedom from symptomatic recurrent biliary obstruction requiring re-intervention was achieved in 108 of 113 patients (95.6, 95%CI = 90.0–98.6%) at study exit for each patient. Per interval analysis yielded the absence of recurrent biliary obstruction in 99.0% of patients at 1 month (n = 99; 95%CI = 97.0–100%), 96.6% of patients at 3 months (n = 77; 95%CI = 92.7–100%), and 93.3% of patients at 6 months (n = 48; 95%CI = 86.8–99.9%). In total, only 5 patients (4.4%) were considered failures of the primary endpoint. Most of these failures (4/5) were due to stent occlusion from tumor ingrowth or overgrowth. Overall technical success rate of stent deployment was 99.2%. There were 2 cases of stent-related adverse events (1.8%). There were no cases of post-procedure stent migration, stent-related perforation, or stent-related deaths. Conclusions This newly designed and marketed biliary SEMS system appears to be effective at relieving biliary obstruction and preventing re-intervention within 6 months of insertion in the overwhelming majority of patients. The device has an excellent safety profile, and associated high technical success rate during deployment. Trial registration The study was registered on clinicaltrials.gov on 14 October 2013 and the study registration number is NCT01962168 . University of Massachusetts Medical School did not participate in the study.

Developing neurons undergo dramatic morphological changes to appropriately migrate and extend axons to make synaptic connections. The microtubule cytoskeleton, made of α/β-tubulin dimers, drives neurite outgrowth, promotes neuronal growth cone responses, and facilitates intracellular transport of critical cargoes during neurodevelopment. TUBA1A constitutes the majority of α-tubulin in the developing brain and mutations to TUBA1A in humans cause severe brain malformations accompanied by varying neurological defects, collectively termed tubulinopathies. Studies of TUBA1A function in mammalian cells have been limited by the presence of multiple genes encoding highly similar tubulin proteins, which leads to α-tubulin antibody promiscuity and makes genetic manipulation challenging. Here, we test mutant tubulin levels and assembly activity and analyze the impact of TUBA1A reduction on growth cone composition, neurite extension, and commissural axon architecture during brain development. We present a novel tagging method for studying and manipulating TUBA1A in cells without impairing tubulin function. Using this tool, we show that a TUBA1A loss-of-function mutation TUBA1AN102D (TUBA1AND), reduces TUBA1A protein levels and prevents incorporation of TUBA1A into microtubule polymers. Reduced Tuba1a α-tubulin in heterozygous Tuba1aND/+ mice leads to grossly normal brain formation except a significant impact on axon extension and impaired formation of forebrain commissures. Neurons with reduced Tuba1a as a result of the Tuba1aND mutation exhibit slower neuron outgrowth compared to controls. Neurons deficient in Tuba1a failed to localize microtubule associated protein-1b (Map1b) to the developing growth cone, likely impacting stabilization of microtubules. Overall, we show that reduced Tuba1a is sufficient to support neuronal migration and cortex development but not commissure formation, and provide mechanistic insight as to how TUBA1A tunes microtubule function to support neurodevelopment.

Mitochondrial superoxide (O2−) production is implicated in aging, neurodegenerative disease, and most recently epilepsy. Yet the specific contribution of neuronal O2− to these phenomena is unclear. Here, we selectively deleted superoxide dismutase-2 (SOD2) in neuronal basic helix-loop-helix transcription factor (NEX)-expressing cells restricting deletion to a subset of excitatory principle neurons primarily in the forebrain (cortex and hippocampus). This resulted in nSOD2 KO mice that lived into adulthood (2–3 months) with epilepsy, selective loss of neurons, metabolic rewiring and a marked mitohormetic gene response. Surprisingly, expression of an astrocytic gene, glial fibrillary acidic protein (GFAP) was significantly increased relative to WT. Further studies in rat primary neuron-glial cultures showed that increased mitochondrial O2−, specifically in neurons, was sufficient to upregulate GFAP. These results suggest that neuron-specific mitochondrial O2− is sufficient to drive a complex and catastrophic epileptic phenotype and highlights the ability of SOD2 to act in a cell-nonautonomous manner to influence an astrocytic response.

Pure perovskite Ba0.90Ca0.10TiO3 ceramics, with a relative density of between 79 and 98% and grain sizes larger than 1 µm, were prepared by solid-state reaction. The dielectric and electrocaloric properties were investigated and discussed considering the density and grain size of the samples. Room temperature impedance measurements show good dielectric properties for all ceramics with relative permittivity between 800 and 1100 and losses of sat = 7.2 µC/cm2 to Psat = 16 µC/cm2). The largest electrocaloric effect was 1.67 K for ceramic with GS = 3 µm at 363 K and electrocaloric responsivity (ζ) was 0.56 K mm/kV. These values are larger than in the case of other similar materials; thus, Ba0.90Ca0.10TiO3 ceramics with a density larger than 90% and grain sizes of a few µms are suitable materials for electrocaloric devices.

Background: The combination of surgery, bacterial spread-out, and artificial cardiopulmonary bypass surfaces results in a release of key inflammatory mediators leading to an overshooting systemic hyper-inflammatory condition frequently associated with compromised hemodynamics and organ dysfunction. A promising approach could be extracorporeal blood purification therapies in combination with IgM enriched immunoglobulin. This approach might perform a balanced control of both hyper and hypo-inflammatory phases as an immune-modulating intervention. Methods: We performed a retrospective observational study of patients with proven infection after cardiac surgery between January 2020 and December 2021. Patients were divided into two groups: (1) the first group (Control Group) followed a standard care approach as recommended by the Surviving Sepsis Campaign Guidelines; The second group (Active Group) underwent extracorporeal blood purification therapy (EBPT) in combination with intravenous administration of IgM enriched immunoglobulin 5 mL/kg die for at least three consecutive days, in conjunction with the standard approach (SSC Guidelines). In addition, ventriculo-arterial (V/A) coupling, Interleukin 6 (IL-6), Endotoxin Activity Assay (EAA), Procalcitonin, White Blood Cells (WBC) counts, Sequential Organ Failure Assessment (SOFA) Score and Inotropic Score were assessed in both two groups at different time points. Results: Fifty-four patients were recruited; 25 were in the Control Group, while 29 participants were in the Active Group. SOFA score significantly improved from baseline [12 (9–16)] until at T3 [8 (3–13)] in the active group; it was associated with a median EAA reduction from 1.03 (0.39–1.20) at T0 to 0.41 (0.2–0.9) at T3 in the active group compared with control group 0.70 (0.50–1.00) at T0 to 0.70 (0.50–1.00) at T3 (p < 0.001). V/A coupling tended to be lower in patients of the active arm ranging from 1.9 (1.2–2.7) at T0 to 0.8 (0.8–2.2) at T3 than in those of the control arm ranging from 2.1 (1.4–2.2) at T0 to 1.75 (1.45–2.1) at T3 (p = 0.099). The hemodynamic improvement over time was associated with evident but no significant decrease in inotropic score in the active group compared with the control group. Changes in EAA value from T0 to T4 were directly and significantly related (r = 0.39, p = 0.006) to those of V/A coupling. Conclusions: EBPT, in combination with IgM enriched immunoglobulin, was associated with a mitigated postoperative response of key cytokines with a significant decrease in IL-6, Procalcitonin, and EAA and was associated with improvement of clinical and metabolic parameters.

Abstract Background Dysregulation in calcium (Ca2+) signaling is a hallmark of chronic lymphocytic leukemia (CLL). While the role of the B cell receptor (BCR) Ca2+ pathway has been associated with disease progression, the importance of the newly described constitutive Ca2+ entry (CE) pathway is less clear. In addition, we hypothesized that these differences reflect modifications of the CE pathway and Ca2+ actors such as Orai1, transient receptor potential canonical (TRPC) 1, and stromal interaction molecule 1 (STIM1), the latter being the focus of this study. Methods An extensive analysis of the Ca2+ entry (CE) pathway in CLL B cells was performed including constitutive Ca2+ entry, basal Ca2+ levels, and store operated Ca2+ entry (SOCE) activated following B cell receptor engagement or using Thapsigargin. The molecular characterization of the calcium channels Orai1 and TRPC1 and to their partner STIM1 was performed by flow cytometry and/or Western blotting. Specific siRNAs for Orai1, TRPC1 and STIM1 plus the Orai1 channel blocker Synta66 were used. CLL B cell viability was tested in the presence of an anti-STIM1 monoclonal antibody (mAb, clone GOK) coupled or not with an anti-CD20 mAb, rituximab. The Cox regression model was used to determine the optimal threshold and to stratify patients. Results Seeking to explore the CE pathway, we found in untreated CLL patients that an abnormal CE pathway was (i) highly associated with the disease outcome; (ii) positively correlated with basal Ca2+ concentrations; (iii) independent from the BCR-PLCγ2-InsP3R (SOCE) Ca2+ signaling pathway; (iv) supported by Orai1 and TRPC1 channels; (v) regulated by the pool of STIM1 located in the plasma membrane (STIM1PM); and (vi) blocked when using a mAb targeting STIM1PM. Next, we further established an association between an elevated expression of STIM1PM and clinical outcome. In addition, combining an anti-STIM1 mAb with rituximab significantly reduced in vitro CLL B cell viability within the high STIM1PM CLL subgroup. Conclusions These data establish the critical role of a newly discovered BCR independent Ca2+ entry in CLL evolution, provide new insights into CLL pathophysiology, and support innovative therapeutic perspectives such as targeting STIM1 located at the plasma membrane.

Abstract Background The comparison of fingerprints by expert latent print examiners generally involves repeating a process in which the examiner selects a small area of distinctive features in one print (a target group), and searches for it in the other print. In order to isolate this key element of fingerprint comparison, we use eye-tracking data to describe the behavior of latent fingerprint examiners on a narrowly defined “find the target” task. Participants were shown a fingerprint image with a target group indicated and asked to find the corresponding area of ridge detail in a second impression of the same finger and state when they found the target location. Target groups were presented on latent and plain exemplar fingerprint images, and as small areas cropped from the plain exemplars, to assess how image quality and the lack of surrounding visual context affected task performance and eye behavior. One hundred and seventeen participants completed a total of 675 trials. Results The presence or absence of context notably affected the areas viewed and time spent in comparison; differences between latent and plain exemplar tasks were much less significant. In virtually all trials, examiners repeatedly looked back and forth between the images, suggesting constraints on the capacity of visual working memory. On most trials where context was provided, examiners looked immediately at the corresponding location: with context, median time to find the corresponding location was less than 0.3 s (second fixation); however, without context, median time was 1.9 s (five fixations). A few trials resulted in errors in which the examiner did not find the correct target location. Basic gaze measures of overt behaviors, such as speed, areas visited, and back-and-forth behavior, were used in conjunction with the known target area to infer the underlying cognitive state of the examiner. Conclusions Visual context has a significant effect on the eye behavior of latent print examiners. Localization errors suggest how errors may occur in real comparisons: examiners sometimes compare an incorrect but similar target group and do not continue to search for a better candidate target group. The analytic methods and predictive models developed here can be used to describe the more complex behavior involved in actual fingerprint comparisons.

El objetivo de este trabajo es presentar el plano arqueológico del sitio Fuerte San José (Península Valdés, Chubut), integrando los análisis de documentación histórica y cartográfica con los resultados de las tres campañas arqueológicas realizadas al sitio. La fragmentación y ambigüedad de la información histórica, así como la baja obstrusividad del registro arqueológico, promovieron que las investigaciones en el Fuerte San José se centren en examinar cómo se organizó el espacio y se habitó dicho asentamiento colonial. En tanto esta condición lo vuelve un caso atípico y complejo en el marco de las investigaciones en arqueología histórica, presentamos en este trabajo el diseño metodológico para abordar la estructuración y uso del espacio donde se habría emplazado el fuerte colonial, atendiendo a los procesos de formación que afectan al sitio, sus consecuencias para el registro arqueológico y la preservación del patrimonio local.

Abstract Background Clinical assays for the assessment of the human epidermal growth factor receptor-2 (HER2) status in breast cancer include immunohistochemistry (IHC) and in situ hybridization (ISH), both of which have limitations. Recent studies have suggested that a more quantitative approach to the measurement of HER2 protein expression may improve specificity in selecting patients for HER-2 targeted therapy. In the current study, we have used HER2 expression in breast cancer cell lines and clinical samples as a model to explore the potential utility of a novel immunodetection technique, using streptavidin coated Phosphor Integrated Dot fluorescent nanoparticles (PID), which can be quantitatively measured using computer analysis. Methods The expression of HER2 protein in cell lines was evaluated with antibody-binding capacity using fluorescence-activated cell sorting (FACS) for comparison with PID measurements to test for correlations with existing quantitative protein analysis methodologies. Various other analytic validation tests were also performed, including accuracy, precision, sensitivity, robustness and reproducibility. A methods comparison study investigated correlations between PID versus IHC and ISH in clinical samples. Lastly, we measured HER2 protein expression using PID in the pretreatment biopsies from 34 HER2-positive carcinomas that had undergone neoadjuvant trastuzumab-based chemotherapy. Results In the analytic validation, PID HER2 measurements showed a strong linear correlation with FACS analysis in breast cell lines, and demonstrated significant correlations with all aspects of precision, sensitivity, robustness and reproducibility. PID also showed strong correlations with conventional HER2 testing methodologies (IHC and ISH). In the neoadjuvant study, patients with a pathologic complete response (pCR) had a significantly higher PID score compared with patients who did not achieve a pCR (p = 0.011), and was significantly correlated to residual cancer burden (RCB) class (p = 0.026, R2 = 0.9975). Conclusions Analytic testing of PID showed that it may be a viable testing methodology that could offer advantages over other experimental or conventional biomarker diagnostic methodologies. Our data also suggests that PID quantitation of HER2 protein may offer an improvement over conventional HER2 testing in the selection of patients who will be the most likely to benefit from HER2-targeted therapy. Further studies with a larger cohort are warranted.

Background: The literature has shown a significant association between traumatic experiences and eating psychopathology, showing a greater symptomatology in patients with trauma history. Less is known about the associations between trauma and cognitive schemas, and personality traits and the differences between childhood and adulthood trauma experiences. Thus, this paper aims to assess the clinical and psychological characteristics of eating disorder (ED) patients, looking for differences between patients without a history of trauma and patients with trauma experiences, as well as at possible differences between exposure in childhood, adulthood, or repeated events. Another aim of the paper is to evaluate the possible mediation role of cognitive schemas and personality traits in the relationship between early trauma and eating psychopathology.Methods: From January to November 2020, 115 consecutive inpatients admitted for a specific multidisciplinary ED treatment in a dedicated Unit were evaluated for trauma, differentiating between trauma occurring in childhood and adulthood. The subjects were evaluated for early maladaptive schemas (EMS), personality traits, trauma symptomatology, quality of life, and specific psychopathologies linked to EDs. Mediation analyses between childhood and adulthood trauma and eating psychopathology were performed, with EMS and personality traits as mediators.Results: Patients with a history of trauma showed higher physical and psychological symptomatology scores, with a more impaired clinical profile in patients with both childhood and adulthood trauma exposure. The mediation analysis showed a specific mediator role for the “disconnection and rejection (DR)” EMS factor in the relationship between childhood trauma (cT) and eating psychopathology.Conclusion: Trauma experiences are associated with more severe clinical symptomatology in EDs and may need a specific assessment in patients with failed outpatient standard treatments. Specific cognitive schemas linked to DR domain should be evaluated in treatments for ED patients with history of trauma due to the mediation role between trauma and eating psychopathology. The need for outcome studies about treatment approaches for ED patients with history of trauma is discussed.

Objectives In Italy, the pandemic of COVID-19 resulted in congestion of hospitals and laboratories and probably determined an underestimation of the number of infected subjects, as the molecular diagnosis of SARS-CoV-2 infection was mainly performed on hospitalised patients. Therefore, limited data are available about the number of asymptomatic/paucisymptomatic subjects in the general population across time. To understand SARS-CoV-2 infection in the general population, we have developed a cross-sectional study (the ‘UNIversity against CORoNavirus study’) to investigate infection trends in asymptomatic/paucisymptomatic subjects in Milan (Italy), between March and June 2020.Participants The study population included 2023 subjects asymptomatic at the enrolment.Primary outcome measures A nasal mid-turbinate swab for the detection of SARS-CoV-2 RNA and blood specimen for testing serum antibodies (immunoglobulin M (IgM) and IgG) were collected.Results Subjects showing positivity for the SARS-CoV-2 RNA and/or for anti-SARS-CoV-2 Ig is 237 (11.7%). Only 1.2% (n=25) of the total population had a positive nasal swab for SARS-CoV-2 and the large majority (21/25) of them were observed in March. A total of 226 subjects (11%) had IgM (n=19; 0.9%), IgG (n=155; 7.7%) or both (n=52; 2.6%) against SARS-CoV-2. Subjects with a present or past SARS-CoV-2 infection did not differ from other subjects as regards the number of cohabiting family members, travels, fever and upper and lower respiratory infection episodes.Conclusions Results from the present study support the hypothesis that the actual spread of the virus in Lombardy was underestimated in the official records. However, as it is not known how long Ig persist, numbers should be taken cautiously.

In this work we report for the first time a mathematical approach to model the behaviour of a single oleosome (oil body) within a seed cellular environment. To describe the behaviour of the oleosome membrane, we adopted a dynamical continuum model based on the principle of the virtual work where the intrinsic energy of the lipid membrane is assumed to obey the Canham–Helfrich model with the rheology of the viscous interface governed by the Boussinesq–Scriven law. To show the suitability of this approach to study the mechanical behaviour of oleosomes, we present some numerical simulations of a single oleosome deformation occurring under in vivo and ex vivo conditions. This work aims to show how the mathematical and computational modelling allows studying the impact of otherwise hard-to-measure physical quantities in this field of biological applications.

Latent fingerprint examiners sometimes come to different conclusions when comparing fingerprints, and eye-gaze behavior may help explain these outcomes. missed identifications (missed IDs) are inconclusive, exclusion, or No Value determinations reached when the consensus of other examiners is an identification. To determine the relation between examiner behavior and missed IDs, we collected eye-gaze data from 121 latent print examiners as they completed a total 1444 difficult (latent-exemplar) comparisons. We extracted metrics from the gaze data that serve as proxies for underlying perceptual and cognitive capacities. We used these metrics to characterize potential mechanisms of missed IDs: Cursory Comparison and Mislocalization. We find that missed IDs are associated with shorter comparison times, fewer regions visited, and fewer attempted correspondences between the compared images. Latent print comparisons resulting in erroneous exclusions (a subset of missed IDs) are also more likely to have fixations in different regions and less accurate correspondence attempts than those comparisons resulting in identifications. We also use our derived metrics to describe one atypical examiner who made six erroneous identifications, four of which were on comparisons intended to be straightforward exclusions. The present work helps identify the degree to which missed IDs can be explained using eye-gaze behavior, and the extent to which missed IDs depend on cognitive and decision-making factors outside the domain of eye-tracking methodologies.

Background and study aims The coronavirus disease 2019 (COVID-19), and measures taken to mitigate its impact, have profoundly affected the clinical care of gastroenterology patients and the work of endoscopy units. We aimed to describe the clinical care delivered by gastroenterologists and the type of procedures performed during the early to peak period of the pandemic. Methods Endoscopy leaders in the New York region were invited to participate in an electronic survey describing operations and clinical service. Surveys were distributed on April 7, 2020 and responses were collected over the following week. A follow-up survey was distributed on April 20, 2020. Participants were asked to report procedure volumes and patient characteristics, as well protocols for staffing and testing for COVID-19. Results Eleven large academic endoscopy units in the New York City region responded to the survey, representing every major hospital system. COVID patients occupied an average of 54.5 % (18 – 84 %) of hospital beds at the time of survey completion, with 14.5 % (2 %-23 %) of COVID patients requiring intensive care. Endoscopy procedure volume and the number of physicians performing procedures declined by 90 % (66 %-98 %) and 84.5 % (50 %-97 %) respectively following introduction of restricted practice. During this period the most common procedures were EGDs (7.9/unit/week; 88 % for bleeding; the remainder for foreign body and feeding tube placement); ERCPs (5/unit/week; for cholangitis in 67 % and obstructive jaundice in 20 %); Colonoscopies (4/unit/week for bleeding in 77 % or colitis in 23 %) and least common were EUS (3/unit/week for tumor biopsies). Of the sites, 44 % performed pre-procedure COVID testing and the proportion of COVID-positive patients undergoing procedures was 4.6 % in the first 2 weeks and up to 19.6 % in the subsequent 2 weeks. The majority of COVID-positive patients undergoing procedures underwent EGD (30.6 % COVID +) and ERCP (10.2 % COVID +). Conclusions COVID-19 has profoundly impacted the operation of endoscopy units in the New York region. Our data show the impact of a restricted emergency practice on endoscopy volumes and the proportion of expected COVID positive cases during the peak time of the pandemic.

Abstract Background Valve-in-valve transcatheter aortic valve implantation for degenerated aortic bioprostheses is an effective option for patients at high risk for redo surgery, even if it may be burdened by complications more common in specific settings, such as, coronary artery obstruction. Case presentation We present the case of a Caucasic 84-year-old woman with degeneration of a previously implanted aortic Mitroflow bioprosthesis. She underwent a valve-in-valve transcatheter aortic valve implantation with a CoreValve® bioprosthesis. End-procedure coronary angiography demonstrated maintained perfusion of both coronary arteries. However, few hours later, she experienced sudden cardiac death. An autopsy showed that Mitroflow prosthesis leaflets were higher than the left main coronary ostium, and no other possible cause for the sudden death. Fatality was thus ascribed to left main coronary ostium obstruction due to apposition of the Mitroflow leaflet pushed upward by the late expansion of CoreValve®. Conclusions Coronary artery obstruction is a frequently fatal complication which usually presents just after valve implantation, but, as reported in our case, it may also have a delayed presentation. Accurate patient’s selection and intraoperative preventive measures can reduce this eventuality.

In this paper we will report on the importance of 3D documentation as a tool for study and communication in Cultural Heritage, with particular reference to the experience grown up at Centro Conservazione e Restauro La Venaria Reale (in the text: CCR La Venaria Reale) and to its application on Egyptian artefacts. We will focus on the purpose-built virtual viewer, set up in order to solve specific operational needs of the working group. We will consider for that significant case studies for innovation that 3D technology has brought in terms of streamlining processes and sharing results. We will also focus on technical advantages obtained by the realization of a 3D model of the remains of a 22nd dynasty cartonnage, found by the Italian Archaeological Mission at the area of the Temple of Millions of Years of Amenhotep II (Luxor, West bank, Egypt), and on the benefit in using 3D documentation on archaeological excavations.

Abstract Background The optimal approach to the drainage of malignant obstruction at the liver hilum remains uncertain. We aim to compare percutaneous transhepatic biliary drainage (PTBD) to endoscopic retrograde cholangiography (ERC) as the first intervention in patients with cholestasis due to suspected malignant hilar obstruction (MHO). Methods The INTERCPT trial is a multi-center, comparative effectiveness, randomized, superiority trial of PTBD vs. ERC for decompression of suspected MHO. One hundred and eighty-four eligible patients across medical centers in the United States, who provide informed consent, will be randomly assigned in 1:1 fashion via a web-based electronic randomization system to either ERC or PTBD as the initial drainage and, if indicated, diagnostic procedure. All subsequent clinical interventions, including crossover to the alternative procedure, will be dictated by treating physicians per usual clinical care. Enrolled subjects will be assessed for successful biliary drainage (primary outcome measure), adequate tissue diagnosis, adverse events, the need for additional procedures, hospitalizations, and oncological outcomes over a 6-month follow-up period. Subjects, treating clinicians and outcome assessors will not be blinded. Discussion The INTERCPT trial is designed to determine whether PTBD or ERC is the better initial approach when managing a patient with suspected MHO, a common clinical dilemma that has never been investigated in a randomized trial. Trial registration ClinicalTrials.gov, Identifier: NCT03172832. Registered on 1 June 2017.

The physical–chemical properties of the surface of DNA microarrays and biosensors play a fundamental role in their performance, affecting the signal’s amplitude and the strength and kinetics of binding. We studied how the interaction parameters vary for hybridization of complementary 23-mer DNA, when the probe strands are immobilized on different copolymers, which coat the surface of an optical, label-free biosensor. Copolymers of N, N-dimethylacrylamide bringing either a different type or density of sites for covalent immobilization of DNA probes, or different backbone charges, were used to functionalize the surface of a Reflective Phantom Interface multispot biosensor made of a glass prism with a silicon dioxide antireflective layer. By analyzing the kinetic hybridization curves at different probe surface densities and target concentrations in solution, we found that all the tested coatings displayed a common association kinetics of about 9 × 104 M−1·s−1 at small probe density, decreasing by one order of magnitude close to the surface saturation of probes. In contrast, both the yield of hybridization and the dissociation kinetics, and hence the equilibrium constant, depend on the type of copolymer coating. Nearly doubled signal amplitudes, although equilibrium dissociation constant was as large as 4 nM, were obtained by immobilizing the probe via click chemistry, whereas amine-based immobilization combined with passivation with diamine carrying positive charges granted much slower dissociation kinetics, yielding an equilibrium dissociation constant as low as 0.5 nM. These results offer quantitative criteria for an optimal selection of surface copolymer coatings, depending on the application.

Diagnostic physical methods are increasingly applied to Cultural Heritage both for scientific investigations and conservation purposes. In particular, the X-ray imaging techniques of computed tomography (CT) and digital radiography (DR) are non-destructive investigation methods to study an object, being able to give information on its inner structure. In this paper, we present the results of the X-ray imaging study on an ancient Egyptian statuette (Late Period 722–30 BCE) belonging to the collection of Museo Egizio in Torino and representing an Egyptian goddess called Taweret, carved on wood and gilded with some colored details. Since few specific studies have been focused on materials and techniques used in Ancient Egypt for gilding, a detailed investigation was started in order to verify the technical features of the decoration in this sculpture. Specifically, DR and CT analyses have been performed at the Centro Conservazione e Restauro “La Venaria Reale” (CCR), with a new high resolution flat-panel detector, that allowed us to perform tomographic analysis reaching a final resolution better than the one achievable with the previous apparatus operating in the CCR.

Uranium (U) is a heavy metal used in military and industrial settings, with a large portion being mined from the Southwest region of the United States. Uranium has uses in energy and military weaponry, but the mining process has released U into soil and surface waters that may pose threats to human and environmental health. The majority of literature regarding U’s human health concern focuses on outcomes based on unintentional ingestion or inhalation, and limited data are available about its influence via cutaneous contact. Utilizing skin dermis cells, we evaluated U’s topical chemotoxicity. Employing soluble depleted uranium (DU) in the form of uranyl nitrate (UN), we hypothesized that in vitro exposure of UN will have cytotoxic effects on primary dermal fibroblasts by affecting cell viability and metabolic activity and, further, may delay wound healing aspects via altering cell proliferation and migration. Using environmentally relevant levels of U found in water (0.1 μM to 100 μM [UN]; 23.8–23,800 ppb [U]), we quantified cellular mitosis and migration through growth curves and in vitro scratch assays. Cells were exposed from 24 h to 144 h for a time-course evaluation of UN chemical toxicity. The effects of UN were observed at concentrations above and below the Environmental Protection Agency threshold for safe exposure limits. UN exposure resulted in a dose-dependent decrease in the viable cell count; however, it produced an increase in metabolism when corrected for the viable cells present. Furthermore, cellular proliferation, population doubling, and percent closure was hindered at levels ≥10 μM UN. Therefore, inadvertent exposure may exacerbate pre-existing skin diseases in at-risk demographics, and additionally, it may substantially interfere in cutaneous tissue repair processes.

Ciguatera fish poisoning (CFP) and neurotoxic shellfish poisoning syndromes are induced by the consumption of seafood contaminated by ciguatoxins and brevetoxins. Both toxins cause sensory symptoms such as paresthesia, cold dysesthesia and painful disorders. An intense pruritus, which may become chronic, occurs also in CFP. No curative treatment is available and the pathophysiology is not fully elucidated. Here we conducted single-cell calcium video-imaging experiments in sensory neurons from newborn rats to study in vitro the ability of Pacific-ciguatoxin-2 (P-CTX-2) and brevetoxin-1 (PbTx-1) to sensitize receptors and ion channels, (i.e., to increase the percentage of responding cells and/or the response amplitude to their pharmacological agonists). In addition, we studied the neurotrophin release in sensory neurons co-cultured with keratinocytes after exposure to P-CTX-2. Our results show that P-CTX-2 induced the sensitization of TRPA1, TRPV4, PAR2, MrgprC, MrgprA and TTX-r NaV channels in sensory neurons. P-CTX-2 increased the release of nerve growth factor and brain-derived neurotrophic factor in the co-culture supernatant, suggesting that those neurotrophins could contribute to the sensitization of the aforementioned receptors and channels. Our results suggest the potential role of sensitization of sensory receptors/ion channels in the induction or persistence of sensory disturbances in CFP syndrome.

Innovative technical solutions to realize optical biosensors with improved performance are continuously proposed. Progress in material fabrication enables developing novel substrates with enhanced optical responses. At the same time, the increased spectrum of available biomolecular tools, ranging from highly specific receptors to engineered bioconjugated polymers, facilitates the preparation of sensing surfaces with controlled functionality. What remains often unclear is to which extent this continuous innovation provides effective breakthroughs for specific applications. In this review, we address this challenging question for the class of label-free optical biosensors, which can provide a direct signal upon molecular binding without using secondary probes. Label-free biosensors have become a consolidated approach for the characterization and screening of molecular interactions in research laboratories. However, in the last decade, several examples of other applications with high potential impact have been proposed. We review the recent advances in label-free optical biosensing technology by focusing on the potential competitive advantage provided in selected emerging applications, grouped on the basis of the target type. In particular, direct and real-time detection allows the development of simpler, compact, and rapid analytical methods for different kinds of targets, from proteins to DNA and viruses. The lack of secondary interactions facilitates the binding of small-molecule targets and minimizes the perturbation in single-molecule detection. Moreover, the intrinsic versatility of label-free sensing makes it an ideal platform to be integrated with biomolecular machinery with innovative functionality, as in case of the molecular tools provided by DNA nanotechnology.

Mountain lakes provide some fundamental ecosystem services (i.e., water supply for drinking and energy production) and have an enormous aesthetic and conservation value. Ecological knowledge on mountain lakes, however, is still scarce and limited to a few geographical areas and mainly to abiotic features. To fill this gap, a limnological campaign was carried out on 19 lakes of the Mont Avic Natural Park (Aosta, Western Italian Alps). Bathymetric maps of the lakes are provided in this paper, as is data on the lakes’ physical properties, chemistry, nano- and pico-plankton, zooplankton, littoral macroinvertebrates, amphibians and introduced fish. The aim of this study was to create a reference database of ecological data for the development of new studies and conservation measures/actions. To this end, ecological data are discussed from both a limnological and a conservation perspective, allowing for the identification of major threats affecting the lakes in the protected area. Despite local threats which include water exploitation, organic pollution, and introduced fish, water quality was good. Lake biota can however be affected by such threats, in particular introduced fish (Salmonidae and Cyprinidae), representing a challenging conservation problem.

Background and study aims Fully covered self-expanding metal stents (FCSEMS) have been used to treat refractory pancreatic duct strictures. We aimed to evaluate the feasibility, safety, and efficacy of FCSEMS in chronic pancreatitis with refractory pancreatic duct strictures. Patients and methods This was a retrospective multicenter cases series of patients who underwent endoscopic retrograde cholangiopancreatography (ERCP) with FCSEMS placement in the main pancreatic duct (MPD) at five tertiary care centers between February 2010 and June 2016. Primary endpoints were technical success, clinical success, and procedure-related morbidity. Secondary endpoints were pain relief at the end of follow-up and resolution of the pancreatic stricture on ERCP. Results Thirty-three patients with previously drained stents, 76 % of whom were male, underwent ERCP with FCSEMS placement. Mean duration of follow-up was 14 months. All of the patients had prior therapy. The technical success rate for FCSEMS placement was 100 % (n = 33) and the clinical success rate was 93 % (was n = 31). Stents were removed after a median duration of 14.4 weeks. After stent removal, the diameter of the narrowest MPD stricture had increased significantly from 1 mm to 4.5 mm (P

Anthropogenic volatile organic compounds (AVOCs) represent the third largest contribution in gaseous emissions in the urban and peri-urban region of Santiago, the capital of Chile. Some of these compounds are toxic or mutagenic, cause serious damage to human health, and decrease plant growth and development. There is little international information related to atmospheric AVOCs in leaf content from trees exposed to specific sources of pollution, and to our knowledge, there is no research on this topic in Chile. The purpose of this work was to study the leaf content of AVOCs from the Organic Range of Gasoline (ORG: range 6–10 C) emitted by local traffic during the austral summer and spring seasons in leaves of two exotic tree species (Liriodendron tulipifera and Platanus × acerifolia). Leaf samples collected around 2 meters height above the ground were pulverized with a cryogenic mill and eleven chemical components were quantified (toluene, 1,2,4-trimethylbenzene (1,2,4-TMB), styrene, ethylbenzene, ortho, meta and para-xylenes, naphthalene, 1,3,5-trimethylbenzene (1,3,5-TMB), isopropylbenzene, and trichloroethene) using GC-MSD MSD. Benzene was detected but not quantified, because it was always under the quantification limit of the technique. Differences in concentrations were found for type of site exposure, season and tree species. The differences found in leaf content of AVOCs in P. × acerifolia exposed to vehicle traffic suggest that the concentration of these contaminants in leaves may be due to AVOC capturing. Considering the content of AVOCs in leaves and not in the whole individual tree, L. tulipifera presented a higher concentration of total AVOCs than P. × acerifolia for both seasons. The Prop-Equiv and OFP of L. tulipifera were very high in summer, being 13.6 and 14.8 times greater, respectively, than the corresponding values for P. × acerifolia.

Based on my research on the structuring of interethnic relations in the framework of the Spanish colonization of the Patagonian coast in the late 18th century, in this paper I will present information about the genealogy of Cacica María. I will offer arguments for not only her tehuelche origin, but about the ties that her family holds with the aforementioned colonial enclaves, especially with the settlement of Puerto Deseado (Santa Cruz province). In this regard, I am interested in incorporating both unpublished historical information as well as sources edited, although scarcely deepened in the bibliography consulted. Beyond the genealogy of the cacica, it also sought to contribute to knowledge about both intra and interethnic relations as well as the territories of southern tehuelches in the transition from the 18th to 19th centuries, marked by deep political and social changes.

BackgroundTrypanosoma cruzi, the agent of Chagas disease, is a protozoan parasite transmitted to humans by blood-sucking triatomine vectors. However, and despite its utmost biological and epidemiological relevance, T. cruzi development inside the digestive tract of the insect remains a poorly understood process.Methods/principle findingsHere we showed that Gp35/50 kDa mucins, the major surface glycoproteins from T. cruzi insect-dwelling forms, are involved in parasite attachment to the internal cuticle of the triatomine rectal ampoule, a critical step leading to its differentiation into mammal-infective forms. Experimental evidence supporting this conclusion could be summarized as follows: i) native and recombinant Gp35/50 kDa mucins directly interacted with hindgut tissues from Triatoma infestans, as assessed by indirect immunofluorescence assays; ii) transgenic epimastigotes over-expressing Gp35/50 kDa mucins on their surface coat exhibited improved attachment rates (~2-3 fold) to such tissues as compared to appropriate transgenic controls and/or wild-type counterparts; and iii) certain chemically synthesized compounds derived from Gp35/50 kDa mucins were able to specifically interfere with epimastigote attachment to the inner lining of T. infestans rectal ampoules in ex vivo binding assays, most likely by competing with or directly blocking insect receptor(s). A solvent-exposed peptide (smugS peptide) from the Gp35/50 kDa mucins protein scaffolds and a branched, Galf-containing trisaccharide (Galfβ1-4[Galpβ1-6]GlcNAcα) from their O-linked glycans were identified as main adhesion determinants for these molecules. Interestingly, exogenous addition of a synthetic Galfβ1-4[Galpβ1-6]GlcNAcα derivative or of oligosaccharides containing this structure impaired the attachment of Dm28c but not of CL Brener epimastigotes to triatomine hindgut tissues; which correlates with the presence of Galf residues on the Gp35/50 kDa mucins' O-glycans on the former but not the latter parasite clone.Conclusion/significanceThese results provide novel insights into the mechanisms underlying T. cruzi-triatomine interplay, and indicate that inter-strain variations in the O-glycosylation of Gp35/50 kDa mucins may lead to differences in parasite differentiation and hence, in parasite transmissibility to the mammalian host. Most importantly, our findings point to Gp35/50 kDa mucins and/or the Galf biosynthetic pathway, which is absent in mammals and insects, as appealing targets for the development of T. cruzi transmission-blocking strategies.

BACKGROUND:TolT was originally described as a Trypanosoma cruzi molecule that accumulated on the trypomastigote flagellum bearing similarity to bacterial TolA colicins receptors. Preliminary biochemical studies indicated that TolT resolved in SDS-PAGE as ~3-5 different bands with sizes between 34 and 45 kDa, and that this heterogeneity could be ascribed to differences in polypeptide glycosylation. However, the recurrent identification of TolT-deduced peptides, and variations thereof, in trypomastigote proteomic surveys suggested an intrinsic TolT complexity, and prompted us to undertake a thorough reassessment of this antigen. METHODS/PRINCIPLE FINDINGS:Genome mining exercises showed that TolT constitutes a larger-than-expected family of genes, with at least 12 polymorphic members in the T. cruzi CL Brener reference strain and homologs in different trypanosomes. According to structural features, TolT deduced proteins could be split into three robust groups, termed TolT-A, TolT-B, and TolT-C, all of them showing marginal sequence similarity to bacterial TolA proteins and canonical signatures of surface localization/membrane association, most of which were herein experimentally validated. Further biochemical and microscopy-based characterizations indicated that this grouping may have a functional correlate, as TolT-A, TolT-B and TolT-C molecules showed differences in their expression profile, sub-cellular distribution, post-translational modification(s) and antigenic structure. We finally used a recently developed fluorescence magnetic beads immunoassay to validate a recombinant protein spanning the central and mature region of a TolT-B deduced molecule for Chagas disease serodiagnosis. CONCLUSION/SIGNIFICANCE:This study unveiled an unexpected genetic and biochemical complexity within the TolT family, which could be exploited for the development of novel T. cruzi biomarkers with diagnostic/therapeutic applications.

Na medicina, para combater o câncer, são utilizados tratamentos como quimioterapia e radioterapia, formas comuns para matar as células cancerosas e limitar os danosas células saudáveis adjacentes. Entretanto, na presença de células tronco cancer´ıgenas pode ocorrer o chamado paradoxo do crescimento do tumor, isto é, ocorre o crescimento tumoral acelerado com o aumento da morte celular. Neste trabalho, apresentamos um modelo de autômatos celulares tridimensional para simular a evolução de um câncer em presença de células cancer´ıgenas e celulas-tronco cancer´ıgenas. Este modelo aqui apresentado mostra como uma simples abordagem matemática simula a ocorrência do paradoxo do crescimento tumoral, fornecendo uma poss´ıvel razão da causa do mesmo e mostrando assim, o paradoxo como uma situação esperada.

Red tides involving Karenia brevis expose humans to brevetoxins (PbTxs). Oral exposition triggers neurotoxic shellfish poisoning, whereas inhalation induces a respiratory syndrome and sensory disturbances. No curative treatment is available and the pathophysiology is not fully elucidated. Protease-activated receptor 2 (PAR2), cathepsin S (Cat-S) and substance P (SP) release are crucial mediators of the sensory effects of ciguatoxins (CTXs) which are PbTx analogs. This work explored the role of PAR2 and Cat-S in PbTx-1-induced sensory effects and deciphered the signaling pathway involved. We performed calcium imaging, PAR2 immunolocalization and SP release experiments in monocultured sensory neurons or co-cultured with keratinocytes treated with PbTx-1 or P-CTX-2. We demonstrated that PbTx-1-induced calcium increase and SP release involved Cat-S, PAR2 and transient receptor potential vanilloid 4 (TRPV4). The PbTx-1-induced signaling pathway included protein kinase A (PKA) and TRPV4, which are compatible with the PAR2 biased signaling induced by Cat-S. Internalization of PAR2 and protein kinase C (PKC), inositol triphosphate receptor and TRPV4 activation evoked by PbTx-1 are compatible with the PAR2 canonical signaling. Our results suggest that PbTx-1-induced sensory disturbances involve the PAR2-TRPV4 pathway. We identified PAR2, Cat-S, PKA, and PKC that are involved in TRPV4 sensitization induced by PbTx-1 in sensory neurons.

The data in this article supports the research paper entitled “Interexaminer variation of minutia markup on latent fingerprints” [1]. The data in this article describes the variability in minutia markup during both analysis of the latents and comparison between latents and exemplars. The data was collected in the “White Box Latent Print Examiner Study,” in which each of 170 volunteer latent print examiners provided detailed markup documenting their examinations of latent-exemplar pairs of prints randomly assigned from a pool of 320 pairs. Each examiner examined 22 latent-exemplar pairs; an average of 12 examiners marked each latent. Keywords: Biometrics, Latent fingerprint examination, Fingermark, ACE-V, Repeatability, Reproducibility

Primary hyperparathyroidism (PHPT) is a clinical condition characterized by overactive parathyroid gland secretion of parathyroid hormone with concurrent alteration of the phosphocalcemic metabolism. We present a literature review on primary hyperparathyroidism addressing key on clinical presentation, causes, medical and surgical treatment at the best of our knowledge. Based on this review we confirm the role of serum calcium and serum level examination, as well as we define the definitive treatment for PHPT being parathyroidectomy. In case of contraindication for surgery, medical treatment can play a relevant role.