The medieval bronze doors of San Zeno, Verona: combining material analyses and art history.

The bronze doors of the Basilica of San Zeno in Verona, Italy, are a special case in art history research. They were made by several workshops during the twelfth century: stylistically, two to three workshops were assumed to produce the metal parts of the door. However, it is still unclear when exactly and if this interpretation can be supported by the chemical composition of the metal. In this research we aimed to verify the art history interpretation by identifying the alloy composition of each individual metal plate. The composition of the supporting wooden structures are discussed. A portable ED-XRF instrument and optical microscopes were used to analyse and document the doors non-invasively. The doors were also photographed to produce high resolution orthophotos and 3D models. We can confirm that the metal parts of the doors were made of leaded tin-bronze as well as leaded brass and mounted on a wooden structure mainly made of spruce and oak wood. Chemically, two/three different groups of alloys have been identified, which can be associated with two or three different workshops, and which largely correspond to the stylistic interpretation. Supplementary Information: The online version contains supplementary material available at 10.1186/s40494-024-01143-2.

Circulating myomiRNAs as biomarkers in patients with Cushing's syndrome.

PURPOSE: Impairment of skeletal muscle mass and strength affects 40-70% of patients with active Cushing's syndrome (CS). Glucocorticoid excess sustains muscle atrophy and weakness, while muscle-specific microRNAs (myomiRs) level changes were associated with muscle organization and function perturbation. The aim of the current study is to explore changes in circulating myomiRs in CS patients compared to healthy controls and their involvement in IGFI/PI3K/Akt/mTOR pathway regulation in skeletal muscle. METHODS: C2C12, mouse myocytes, were exposed to hydrocortisone (HC), and atrophy-related gene expression was investigated by RT-qPCR, WB and IF to assess HC-mediated atrophic signalling. miRNAs were evaluated in HC-treated C2C12 by PCR Arrays. MyomiRs significantly overexpressed in C2C12 were investigated in 37 CS patients and 24 healthy controls serum by RT-qPCR. The anti-anabolic role of circulating miRNAs significantly upregulated in CS patients was explored in C2C12 by investigating the IGFI/PI3K/Akt/mTOR pathway regulation. RESULTS: HC induced higher expression of atrophy-related genes, miR-133a-3p, miR-122-5p and miR-200b-3p in C2C12 compared to untreated cells. Conversely, the anabolic IGFI/PI3K/Akt/mTOR signalling was reduced and this effect was mediated by miR-133a-3p. In CS patients miR-133a-3p and miR-200b-3p revealed higher circulating levels (p < 0.0001, respectively) compared to controls. ROC curves for miR-133a-3p (AUC 0.823, p < 0.0001) and miR-200b-3p (AUC 0.850, p < 0.0001) demonstrated that both myomiRs represent potential biomarkers to discriminate between CS and healthy subjects. Pearson's correlation analysis revealed that circulating levels of miR-133a-3p are directly correlated with 24 h urinary-free cortisol level (r = 0.468, p = 0.004) in CS patients. CONCLUSIONS: HC induces atrophic signals by miR-133a-3p overexpression in mouse myocytes and humans. Circulating miR-133a-3p is promising biomarkers of hypercortisolism.

Storage and Learning Phase Transitions in the Random-Features Hopfield Model.

The Hopfield model is a paradigmatic model of neural networks that has been analyzed for many decades in the statistical physics, neuroscience, and machine learning communities. Inspired by the manifold hypothesis in machine learning, we propose and investigate a generalization of the standard setting that we name random-features Hopfield model. Here, P binary patterns of length N are generated by applying to Gaussian vectors sampled in a latent space of dimension D a random projection followed by a nonlinearity. Using the replica method from statistical physics, we derive the phase diagram of the model in the limit P,N,D→∞ with fixed ratios α=P/N and α_{D}=D/N. Besides the usual retrieval phase, where the patterns can be dynamically recovered from some initial corruption, we uncover a new phase where the features characterizing the projection can be recovered instead. We call this phenomena the learning phase transition, as the features are not explicitly given to the model but rather are inferred from the patterns in an unsupervised fashion.

Excitonic absorption and defect-related emission in three-dimensional MoS2 pyramids.

MoS2 micro-pyramids have demonstrated interesting properties in the fields of photonics and non-linear optics. In this work, we show the excitonic absorption and cathodoluminescence (CL) emission of MoS2 micro-pyramids grown by chemical vapor deposition (CVD) on SiO2 substrates. The excitonic absorption was obtained at room and cryogenic temperatures by taking advantage of the cathodoluminescence emission of the SiO2 substrate. We detected the CL emission related to defect intra-gap states, localized at the pyramid edges and with an enhanced intensity at the pyramid basal vertices. The photoluminescence and absorption analysis provided the Stokes shift of both the A and B excitons in the MoS2 pyramids. This analysis provides new insights into the optical functionality of MoS2 pyramids. This method can be applied to other 3D structures within the 2D materials family.

Lesiones de potencial maligno incierto (B3): nuestra experiencia en el Instituto Alexander Fleming / Lesions of uncertain malignant potential (B3): Our experience at the Alexander Fleming Institute

Objetivo: Revisar la correlación radiopatológica de las lesiones de potencial maligno incierto (B3) de nuestra institución, evaluar la conducta y establecer el porcentaje de subestimación en relación a las lesiones tratadas quirúrgicamente. Material y método: Estudio retrospectivo de la base de datos de procedimientos intervencionistas efectuados en el servicio de diagnóstico por imágenes del Instituto Alexander Fleming entre mayo de 2016 y diciembre de 2019 inclusive. Se incluyeron las pacientes con resultado histológico en la biopsia percutánea de uno o más de los siguientes diagnósticos: atipia epitelial plana (AEP), cicatriz radiada/lesión esclerosante compleja (CR), hiperplasia ductal atípica (HDA), neoplasia lobular clásica (NL), lesión papilar (LP) o tumor phyllodes (TP). Resultados: De 67 pacientes analizadas, el 43.3% se manifestaron en los estudios por imágenes con nódulos y en un 37.3% con microcalcificaciones agrupadas. La LP fue la lesión B3 más frecuente en un 44.8% seguido por la AEP en un 16.4%. El 98.5% de las pacientes presentó adecuada concordancia radiopatológica. Fueron sometidas a cirugía 48 pacientes, las 19 pacientes restantes continuaron con seguimiento clínico radiológico. La anatomía patológica de la pieza quirúrgica reflejó que en un 33.3% hubo subestimación en relación a la biopsia; en más de la mitad de los casos correspondieron a CDIS. Conclusiones: El porcentaje de subestimación con resultado final de CDIS o CDI de bajo grado se encontró dentro de los parámetros hallados en la literatura. Si bien logramos reducir la tasa de cirugías al 71% de pacientes con lesiones B3, una adecuada selección para efectuar exéresis con aguja por sistema de vacío podría reducir aún más el número de cirugías innecesarias y probablemente la tasa de subestimación.

Objective: To review the radiopathological correlation of lesions of uncertain malignant potential (B3) diagnosed in our institution, as well as to evaluate the therapeutic conduct and to establish the percentage of underestimation of the excised lesions. Material and method: This work consists of a retrospective study of the database which in- cludes the interventional procedures performed in the Imaging Department of the Alexander Fleming Institute between May 2016 and December 2019. Patients with a histological outcome in the percutaneous biopsy of one or more of the following diagnosis were included: flat epithelial atypia (FEA), radial scar (RS) /complex sclerosing lesion (CSL), atypical ductal hyperplasia (ADH), classic lobular neo- plasia (LN), papillary lesión (PL) or phyllodes tumor (PT). Results: Out of the 67 analyzed patients, 43.3% were perceived as nodules at imaging examinations and 37.3% as grouped microcalcifications. Papillary lesion was the most frequently diagnosed B3 lesion (44.8%), followed by flat epithelial atypia (16.4%). 98.5% of patients presented an accurate imaging-pathology concordance. 48 patients underwent surgery and the remaining 19 patients continued with clinical and radiological follow-up. The histopathology of the surgical specimen reflected that in 33.3% of the cases there was an underestimation in relation to the percutaneous biopsy; in over half of these cases they corresponded with DCIS. Conclusions: The percentage of underestimation with final diagnosis of DCIS or low grade IDC coincided with the parameters found in current literature. Even though we were able to reduce the surgical rate to 71% of patients with B3 lesions, a proper selection of cases which could be candidates for vacuum assisted excisional biopsy could further reduce the number of unnecessary surgeries and probably the un- derestimation rate as well.

Influence of shrub willow buffers strategically integrated in an Illinois corn-soybean field on soil health and microbial community composition.

Soil serves many important ecological functions and is an integral part of our existence as a society. However, concerns for soil health are growing globally, in part due to the negative impacts of agricultural management on soil resources. The production of perennial bioenergy crops on marginal land in row-crop production systems is one solution that could improve land-use efficiency and address the sustainability of cropland management. Because the relationship between crop management and the environment is complex, more research is needed to evaluate the potential benefits perennial bioenergy crop production has on soil health, as well as other ecosystem services. In this study, shrub willow buffers were strategically integrated into a corn-soybean cropping system with the main objective of reducing nitrate-N leaching from grain crop production while producing biomass for bioenergy. Two buffer systems (defined by landscape positions) were included for comparison, one on marginal land with exposure to nitrate-N leaching from upslope grain (southern plots) and one on fertile soils with less nitrate-N leaching potential (northern plots). Evaluation of soil (chemistry, bulk density, microbial community) and shrub willow vegetation properties (fine roots, leaf litter decomposition, and nutrient uptake dynamics), showed that landscape position plays an important role in (1) the dynamics of soil chemical properties, (2) shrub willow's influence and productivity, and (3) the provision of additional ecosystem services such as reductions in nitrous oxide emissions and nitrate-N leaching. In addition, the combination of crop type and landscape position (N-grain, N-willow, S-grain, and S-willow) influenced the species composition of the soil microbial community, resulting in unique and identifiable communities. These results highlight the potential application of shrub willow buffers for ecosystem service provision and support of ecosystem processes; however, understanding the relationship between the microbial community, crop type, and landscape is important for understanding the sustainability of the design.

Native state of natural proteins optimizes local entropy.

The differing ability of polypeptide conformations to act as the native state of proteins has long been rationalized in terms of differing kinetic accessibility or thermodynamic stability. Building on the successful applications of physical concepts and sampling algorithms recently introduced in the study of disordered systems, in particular artificial neural networks, we quantitatively explore how well a quantity known as the local entropy describes the native state of model proteins. In lattice models and all-atom representations of proteins, we are able to efficiently sample high local entropy states and to provide a proof of concept of enhanced stability and folding rate. Our methods are based on simple and general statistical-mechanics arguments, and thus we expect that they are of very general use.

Uso y prescripción de cannabis medicinal por reumatólogos en Argentina / Use and prescription of medical cannabis by rheumatologists in Argentina

El uso y prescripción del cannabis y sus derivados en Reumatología está aún en discusión. La ley de cannabis fue sancionada hace casi 3 años, aunque la reglamentación recién está comenzando. El objetivo de este estudio fue conocer la forma en que el reumatólogo se posiciona frente al uso de cannabis en el marco de su práctica médica. A través de una encuesta realizada durante el Congreso Argentino de Reumatología 2019 se recabó la opinión de 314 médicos que respondieron preguntas acerca del uso, recomendaciones y posturas respecto a la indicación y uso de cannabinoides en su práctica diaria. El 78,3% (246) conocían la existencia de una ley nacional. El 51,6% (162) se mostró en desacuerdo con el uso de cannabinoides en sus pacientes, mientras que el 36,6% (115) respondió estar de acuerdo, el 3,2% (10) refirió estar muy de acuerdo, y 8,6% (27) estaba muy en desacuerdo. Para pacientes con enfermedades reumáticas autoinmunes, el 94,6% (297) refirió que nunca indica cannabinoides, el 4,1% (13) que los indican pocas veces, y el 1,3% (4) algunas veces. Para las enfermedades reumáticas degenerativas, el 90,4% (284) nunca indica cannabinoides, el 6,7% (21) lo hace pocas veces, y el 2,9% (9) lo hace algunas veces. Para la fibromialgia, el 84,4% (265) nunca indica cannabinoides, el 8,3% (26) los indica pocas veces, el 6,4% (20) los indica algunas veces. El principal obstáculo para la prescripción (permitido más de una respuesta) fue no disponer de la suficiente información científica para prescribir (50,3%, 158), el 47,5% (149) contestó que no conoce los componentes de la preparación, el 47,1% (148) no conoce las dosis o la posología, el 41,4% (130) no le resultan confiables los productores, el 38,9% (122) respondió que no le convencen los estudios clínicos en la especialidad. No hubo diferencias significativas entre las variables edad, género, años en la especialidad o lugar de ejercicio y las respuestas descriptas. Conclusión: El uso de cannabis en Reumatología de acuerdo a los especialistas que ejercen en Argentina requiere de un mayor sustento científico y farmacéutico para poder prescribirlo en un marco seguro.

The use and prescription of cannabis and its derivatives in Rheumatology is still under discussion. The cannabis law was enacted near 3 years ago, although the regulation is just beginning. The objective of this study was to know how rheumatologists positions themselves about the use of cannabis in the framework of his medical practice. Through a survey conducted during the 2019 Argentine Congress of Rheumatology, 314 doctors answered questions about the use, recommendations and opinions regarding the indication and use of cannabinoids in their daily practice. 78.3% (246) knew of the existence of a national law. 51.6% (162) disagreed with the use of cannabinoids by their patients, while 36.6% (115) agreed, 3.2% (10) reported to strongly agree, and 8.6% (27) strongly disagreed. For patients with autoimmune rheumatic diseases, 94.6% (297) reported that they never prescribed cannabinoids, 4.1% (13) prescribed them rarely, and 1.3% (4) sometimes. For degenerative rheumatic diseases, 90.4% (284) never prescribed cannabinoids, 6.7% (21) did it rarely, and 2.9% (9) did so sometimes. For fibromyalgia, 84.4% (265) never prescribed cannabinoids, 8.3% (26) prescribed them rarely, 6.4% (20) sometimes. The main obstacle to prescribing (more than one answer allowed) was not having enough scientific information (50.3%, 158), 47.5% (149) were uncertain about the cannabis preparation, 47.1% (148) had no knowledge about doses or posology, 41.4% (130) didn´t trust the producers, 38.9% (122) were no convince by the trials in the field. There were no significant differences between the variables age, gender, years in the specialty or workplace and the responses described. Conclusion: According to specialists in Argentina, the use of cannabis in rheumatology requires more scientific and pharmaceutical data to prescribe cannabinoids in a safer framework.

Disección axilar dirigida: Nuestra experiencia con el uso de suspensión de carbón activado / Target axillary dissection: Our experience with the use of charcoal suspension

Objetivo: Determinar la tasa de identificación intra operatoria por el médico cirujano de los ganglios marcados con suspensión de carbón activado previo a la neoadyuvancia. El objetivo secundario es determinar la concordancia entre los ganglios linfáticos marcados con carbón y aquellos considerados ganglios centinelas. Material y método: Es un estudio retrospectivo desde el año 2016 hasta el año 2020. Se incluyeron 27 pacientes con cáncer de mama en estadios T1 - T3 que realizaron quimioterapia neoadyuvante y con axila con estadio N1 y N2. Los ganglios axilares biopsiados con resultado positivo fueron marcados con suspensión de carbón activado, posteriormente las pacientes realizaron quimioterapia neoadyuvante. Se evaluó la tasa de detección y concordancia del ganglio marcado con el ganglio centinela durante el procedimiento quirúrgico. Resultados: Del total de pacientes en 20 casos se realizó efectivamente la identificación por inspección visual de la suspensión de carbón activado en la cavidad axilar durante la cirugía. La tasa de detección fue del 74%. Del total de 20 pacientes en los cuales se identificó carbón visualmente en el acto quirúrgico, 16 se sometieron a biopsia de ganglio centinela. En 81% de los casos hubo una coincidencia entre el ganglio marcado con carbón y el ganglio centinela. Conclusión: En nuestro trabajo la tasa de detección intraoperatoria de los ganglios marcados con carbón está en concordancia con lo publicado en la literatura. Esto catapulta a este método de marcación como una alternativa factible para realizar una disección axilar dirigida asegurándole al médico cirujano la resección de una ganglio positivo de inicio para su análisis anatomopatológico de respuesta. Hemos comprobado que la marcación con carbón no interfiere con la técnica estándar utilizada para la biopsia de ganglio centinela sino que su uso en conjunto mejora la técnica dignóstica.

Objetive: The aim of this study was to determine the rate of identification of activated charcoal suspension during surgery in positive lymph nodes before neadjuvant chemotherapy. The secondary objetive is to determine the rate of concordance between the marked lymph nodes and the sentinel lymph nodes. Material and method: A retrospective study that goes from the year 2016 - 2020. It includes 27 patients with breast cancer (T1 - T3) and positive lymph nodes (N1 - N2). Patients with biopsy - confirmed nodal metatases were marked with activated charcoal suspension in the sampled node. After this procedure patients underwent neoadjuvant chemotherapy and axillary surgery. The rate of detection and the concordance of the marked lymph node with the sentinel lymph nodes was calculated. Results: Of the 27 patients enrolled in this study in 20, the marked node was detected during surgery. The detection rate was of 74%. Of these 20 patientes, 16 had sentinel node biopsy. There was an 81% rate of concordance between the sentinel lymph node and the tattooed lymph node. Conclusions: In our study, the detection rate of marked lymph node is concordant with the numbers publised by other studies. This shows that axillary lymph node tattooing with activated charcoal suspension is a viable, low cost and precise method when performing targeted axillary dissection. We identified that the tattooing procedure does not affect the standard sentinel node biopsy, in fact, when used together it improves its diagnostic performance.

The treatment with pasireotide in Cushing's disease: effect of long-term treatment on clinical picture and metabolic profile and management of adverse events in the experience of a single center.

PURPOSES: Pasireotide is the first medical therapy officially approved for adult patients with Cushing's disease (CD) experiencing failure of pituitary surgery or not candidates for surgery. The current study aimed at investigating pasireotide effects on clinical picture and metabolic profile in patients enrolled in the phase III CSOM230B2305 trial at Naples center. In addition, the current study focused on safety issues encountered during the study, detailing the management of the different adverse events associated with the treatment with pasireotide in Naples center. METHODS: Fourteen patients entered the study; eight patients, receiving pasireotide for at least 6 months, were considered for the efficacy analysis, whereas the entire cohort of 14 patients was considered for the safety analysis. RESULTS: Full or partial disease control was obtained in 85.7% of patients, according to a "per-protocol" methodology analysis, and in 42.9% of patients, according to an "intention-to-treat" methodology analysis, after 12 months of treatment. A relevant improvement in clinical signs and symptoms, mainly in facial rubor, supraclavicular fat pad, bruising, hirsutism, and muscle strength was observed; body weight, body mass index, and waist circumference significantly reduced, and a slight non-significant reduction was observed in the prevalence of visceral obesity, hypercholesterolemia, and hypertriglyceridemia. Deterioration of glucose metabolism represented the most common adverse event, occurring in 71.4% of patients, and requiring a dietary regimen as first step, metformin therapy and/or long-acting insulin as second step, and short-acting insulin, as third step; no patients discontinued treatment for hyperglycaemia. Additional adverse events of interest were nausea (21.4%), and vomiting (14.3%), spontaneously resolved in few weeks or some months, except in one patient unsuccessfully treated with metoclopramide and ondansetron, and diarrhoea (14.3%), improved with loperamide treatment. Millimetric gallstones and biliary sludge (7.1%) were managed with ursodeoxycholic acid, inducing lithiasis and biliary sludge resolution, whereas hypocortisolism-related adverse events (7.1%) were resolved with a reduction in the pasireotide dose. CONCLUSIONS: The current study on a limited series of patients contributes to confirm that pasireotide may be considered a valid option for treatment of patients with CD, although it requires an appropriate management of adverse events, especially hyperglycaemia.

FATAL cryptococcal meningitis in a child with hyper-immunoglobulin M syndrome, with an emphasis on the agent.

Following a fatal case of Cryptococcus neoformans meningitis in a child with X-linked hyper-immunoglobulin M syndrome (XHIGM), we evaluated the fungal isolate in an experimental infection in a mouse model with respect to microbiology, epidemiology, virulence and response to therapy. The minimum inhibitory concentrations for antifungals in the susceptibility test were 0.5mg/L for amphotericin B, 4.0mg/L for fluconazole and 0.12mg/L for voriconazole. Evaluation of pathogenicity by means of an experimental infection in BALB/c mice showed that fungus isolated from the blood and cerebrospinal fluid of the child was able to disseminate, reaching the spleen, lungs and brain, where it caused significant macroscopic alterations in the size and texture of each organ. Treatment of infected mice with amphotericin B reduced the fungal load in the spleen and lungs, but not in the brain.

Multi-electrode sequential versus single electrode stimulation to elicit the stapedial reflex during cochlear implantation: Correlation with maximum comfort level.

OBJECTIVES: To assess whether electrical stimulation sequentially delivered through 4 electrodes located in different cochlear areas may elicit the stapedial reflex at lower levels compared to single electrode stimulation and to correlate the sequentially obtained values with the maximum comfort level (C-level). PATIENTS AND METHODS: A retrospective study was performed on 35 post-verbal adult patients (age 19-80 years) consecutively implanted in 2 cochlear implant centers, evaluating the level of stimulation (pulse width) necessary to electrically evoke the stapedial reflex with two different stimulation modalities: single electrode versus sequential 4 electrode stimulation. Threshold values were compared with C-level obtained at activation. RESULTS: The average differences of pulse width and C-level were significantly smaller (P<0.0001) when the stapedial reflex was obtained with the sequential stimulation modality and reached statistical significance for every single electrode (P<0.0001). CONCLUSIONS: Stapedial reflex thresholds obtained with sequential stimulation through 4 different electrodes significantly correlate to the C-level obtained at the first setting and may be helpful in defining the upper limit of the dynamic field during initial CI mapping.

Neurophysiological changes after cognitive-motor tasks in Parkinson's disease patients with deep brain stimulation.

Chronic deep brain stimulation (CDBS) is a surgical treatment that reduces the cardinal signs of Parkinson's disease (PD). Although CDBS has been in use for a long time, very little has been reported on its supposed effects on cognition, particularly in relation to implants in the subthalamic nucleus. The results of the rare studies that do exist are controversial, and in many cases the studies have several design flaws. The present study compared cortical activation during three tasks (action execution, action observation and motor imagery) in PD patients with and without subthalamic implants. The study sample consisted of 36 volunteers, divided into three groups: healthy controls, PD patients with CDBS of the subthalamic nucleus, and PD patients without CDBS. Through a quantitative electroencephalogram assessment, absolute beta power was examined to observe the interaction between group and cognitive motor tasks. The electrodes at sites Fp1, Fp2, F7, F8, F3, Fz and F4, located in the prefrontal and frontal regions, were analyzed and a Group x Task interaction (p < 0.05) was observed for all of them. These findings suggest that CDBS of the subthalamic nucleus is efficient in reducing some of the effects of PD in these study tasks. At the same time, the dysfunctions found in several cortical areas, characteristic of PD, limited the effects of the CDBS. The results of this study suggest that CDBS of the subthalamic nucleus can modulate cognitive-motor aspects of PD.

Maxillary Sinus Floor Augmentation Using an Equine-Derived Graft Material: Preliminary Results in 17 Patients.

OBJECTIVE: Sinus floor elevation with lateral approach is probably the most frequently performed reconstructive procedure to rehabilitate posterior maxilla when a bone deficiency is present. Different graft materials have been proposed and tested, often with high clinical performances and predictable results. Histological analysis is required when evaluating new materials. We investigated human biopsies retrieved after sinus floor elevation procedure by histomorphometric evaluation to test the performance of an equine-derived bone grafting material. STUDY DESIGN: Seventeen consecutive patients were enrolled and sinus lift surgeries were performed using an equine bone graft. Six months after surgery, at implant placement, bone samples were collected. Histomorphometry analysis was carried out on decalcified samples. RESULTS: All surgeries were uneventful and no additional grafting was required prior to implant insertion. Forty percent of new bone formation was detected, which represented the most abundant tissue retrieved, followed by the residual graft material (33%) and fibrous tissue (27%). A significant reduction in particles size demonstrates a remodeling activity of the graft material. CONCLUSION: Within the limitations of this study, this equine-derived bone graft proved to be an effective material to induce new bone formation in the sinus floor elevation procedure.

Differential Functional Constraints Cause Strain-Level Endemism in Polynucleobacter Populations.

The adaptation of bacterial lineages to local environmental conditions creates the potential for broader genotypic diversity within a species, which can enable a species to dominate across ecological gradients because of niche flexibility. The genus Polynucleobacter maintains both free-living and symbiotic ecotypes and maintains an apparently ubiquitous distribution in freshwater ecosystems. Subspecies-level resolution supplemented with metagenome-derived genotype analysis revealed that differential functional constraints, not geographic distance, produce and maintain strain-level genetic conservation in Polynucleobacter populations across three geographically proximal riverine environments. Genes associated with cofactor biosynthesis and one-carbon metabolism showed habitat specificity, and protein-coding genes of unknown function and membrane transport proteins were under positive selection across each habitat. Characterized by different median ratios of nonsynonymous to synonymous evolutionary changes (dN/dS ratios) and a limited but statistically significant negative correlation between the dN/dS ratio and codon usage bias between habitats, the free-living and core genotypes were observed to be evolving under strong purifying selection pressure. Highlighting the potential role of genetic adaptation to the local environment, the two-component system protein-coding genes were highly stable (dN/dS ratio, < 0.03). These results suggest that despite the impact of the habitat on genetic diversity, and hence niche partition, strong environmental selection pressure maintains a conserved core genome for Polynucleobacter populations. IMPORTANCE Understanding the biological factors influencing habitat-wide genetic endemism is important for explaining observed biogeographic patterns. Polynucleobacter is a genus of bacteria that seems to have found a way to colonize myriad freshwater ecosystems and by doing so has become one of the most abundant bacteria in these environments. We sequenced metagenomes from locations across the Chicago River system and assembled Polynucleobacter genomes from different sites and compared how the nucleotide composition, gene codon usage, and the ratio of synonymous (codes for the same amino acid) to nonsynonymous (codes for a different amino acid) mutations varied across these population genomes at each site. The environmental pressures at each site drove purifying selection for functional traits that maintained a streamlined core genome across the Chicago River Polynucleobacter population while allowing for site-specific genomic adaptation. These adaptations enable Polynucleobacter to become dominant across different riverine environmental gradients.

An Integrated Landscape Designed for Commodity and Bioenergy Crops for a Tile-Drained Agricultural Watershed.

Locating bioenergy crops on strategically selected subfield areas of marginal interest for commodity agriculture can increase environmental sustainability. Location and choice of bioenergy crops should improve environmental benefits with minimal disruption of current food production systems. We identified subfield soils of a tile-drained agricultural watershed as marginal if they had areas of low crop productivity index (CPI), were susceptible to nitrate-nitrogen (NO-N) leaching, or were susceptible to at least two other forms of environmental degradation (marginal areas). In the test watershed (Indian Creek watershed, IL) with annual precipitation of 852 mm, 3% of soils were CPI areas and 22% were marginal areas. The Soil and Water Assessment Tool was used to forecast the impact of growing switchgrass ( L.), willow ( spp.), and big bluestem ( Vitman) in these subfield areas on annual grain yields, NO-N and sediment exports, and water yield. Simulated conversion of CPI areas from current land use to bioenergy crops had no significant ( 0.05) impact on grain production and reduced NO-N and sediment exports by 5.0 to 6.0% and 3.0%, respectively. Conversion of marginal areas from current land use to switchgrass forecasted the production of 34,000 t of biomass and reductions in NO-N (26.0%) and sediment (33.0%) exports. Alternatively, conversion of marginal areas from current land use to willow forecasted similar reductions as switchgrass for sediment but significantly ( 0.01) lower reductions in annual NO-N export (18.0 vs. 26.0%).

Tongue coating frequency and its colonization by yeasts in chronic kidney disease patients.

The objective of this study was to investigate tongue coating (TC) frequency and its colonization by yeasts in a group of chronic kidney disease (CKD) patients. Clinical examination of the oral mucosa of 33 CKD patients was performed to investigate oral and tongue lesions. TC was diagnosed according to its clinical characteristics. Stimulated saliva and TC samples were collected to verify the salivary flow, and determine yeast frequency, species and counts. TC was found in 18/33 of the patients (54.55 %) and was the most frequent oral lesion found. Of 18 patients with TC, 13 (72.22 %) presented positive cultures for yeasts on the tongue dorsum, and one (5.55 %) in the saliva only. Yeasts were significantly more frequent in the tongue dorsum when compared to the saliva (p = 0.0106). The most frequent yeast species found was C. albicans (55.55 %), while C. parapsilosis comprised 50 % of non-albicans Candida species. This study demonstrated high amounts of yeasts on the cultures from TC samples of CKD patients, strongly suggesting that TC is a clinical representation of a polymicrobial biofilm, which could serve as a gateway for disseminated infection in immunosuppressed patients undergoing frequent hospitalization.

Fusarium spp. is able to grow and invade healthy human nails as a single source of nutrients.

Onychomycosis caused by Fusarium spp. is emerging, but some factors associated with its development remain unclear, such as whether this genus is keratinolytic. The main aim of the present study was to evaluate the ability of Fusarium to use the human nail as a single source of nutrients. We also performed an epidemiological study and antifungal susceptibility testing of Fusarium spp. that were isolated from patients with onychomycosis. The epidemiological study showed that Fusarium species accounted for 12.4 % of onychomycosis cases, and it was the most common among nondermatophyte molds. The most frequent species identified were F. oxysporum (36.5 %), F. solani (31.8 %), and F. subglutinans (8.3 %). Fluconazole was not active against Fusarium spp., and the response to terbinafine varied according to species. Fusarium was able to grow in vitro without the addition of nutrients and invade healthy nails. Thus, we found that Fusarium uses keratin as a single source of nutrients, and the model proposed herein may be useful for future studies on the pathogenesis of onychomycosis.

Porphyrin conjugated SiC/SiOx nanowires for X-ray-excited photodynamic therapy.

The development of innovative nanosystems opens new perspectives for multidisciplinary applications at the frontier between materials science and nanomedicine. Here we present a novel hybrid nanosystem based on cytocompatible inorganic SiC/SiOx core/shell nanowires conjugated via click-chemistry procedures with an organic photosensitizer, a tetracarboxyphenyl porphyrin derivative. We show that this nanosystem is an efficient source of singlet oxygen for cell oxidative stress when irradiated with 6 MV X-Rays at low doses (0.4-2 Gy). The in-vitro clonogenic survival assay on lung adenocarcinoma cells shows that 12 days after irradiation at a dose of 2 Gy, the cell population is reduced by about 75% with respect to control cells. These results demonstrate that our approach is very efficient to enhance radiation therapy effects for cancer treatments.

Cytocompatibility and cellular internalization mechanisms of SiC/SiO2 nanowires.

First evidence of in vitro cytocompatibility of SiC/SiO2 core-shell nanowires is reported. Different internalization mechanisms by adenocarcinomic alveolar basal epithelial cells, monocytic cell line derived from an acute monocytic leukemia, breast cancer cells, and normal human dermal fibroblasts are shown. The internalization occurs mainly for macropinocytosis and sporadically by direct penetration in all cell models considered, whereas it occurred for phagocytosis only in monocytic leukemia cells. The cytocompatibility of the nanowires is proved by the analysis of cell proliferation, cell cycle progression, and oxidative stress on the cells treated with NWs as compared to controls. Reactive oxygen species generation was detected as an early event that then quickly run out with a rapid decrease only in adenocarcinomic alveolar basal epithelial and human dermal fibroblasts cells. In all the cell lines, the intracellular presence of NWs induce the same molecular events but to a different extent: peroxidation of membrane lipids and oxidation of proteins. The NWs do not elicit either midterm (72 h) or long-term (10 days) cytotoxic activity leading to irreversible cellular damages or death. Our results are important in view of a possible use of SiC/SiO2 core-shell structures acting as biomolecule-delivery vectors or intracellular electrodes.