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.

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.

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.

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%).

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.

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.

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.

Silver colloidal nanoparticles: effect on matrix composition and structure of Candida albicans and Candida glabrata biofilms.

AIM: The aim of this study was to assess the effect of different silver nanoparticles (SN) concentrations on the matrix composition and structure of Candida albicans and Candida glabrata biofilms. METHODS AND RESULTS: Candida biofilms were developed in 6-well microtiter plates during 48 h. After, these biofilms were exposed to 13.5 or 54 µg SN ml(-1) for 24 h. Then, extracellular matrices were extracted from biofilms and analysed chemically in terms of proteins, carbohydrates and DNA. To investigate the biofilm structure, scanning electron microscopy (SEM) and epifluorescence microscopy were used. SN interfered with the matrix composition of Candida biofilms tested in terms of protein, carbohydrate and DNA, except for the protein content of C. albicans biofilm. By SEM, Candida biofilms treated with SN revealed structural differences, when compared with the control groups. Further, SN showed a trend of agglomeration within the biofilms. Epifluorescence microscopy images suggest that SN induced damage on cell walls of the Candida isolates tested. CONCLUSIONS: In general, irrespective of concentration, SN affected the matrix composition and structure of Candida biofilms and these findings may be related to the mechanisms of biocide action of SN. SIGNIFICANCE AND IMPACT OF THE STUDY: This study reveals new insights about the behaviour of SN when in contact with Candida biofilms. SN may contribute to the development of therapies to prevent or control Candida infections.

Achieving the Great Lakes Initiative mercury limits in oil refinery effluent.

To meet the stringent Great Lakes Initiative (GLI) wastewater discharge mercury (Hg) limit of 1.3 ppt (ng/L), mercury removal technologies need to be identified and investigated. The goals of this study were to (1) identify and assess available wastewater treatment technologies for mercury removal from an oil refinery wastewater; and (2) conduct bench-scale tests to provide comparable, transparent, and uniform results to assess their performance at low mercury concentrations. The study found that many tested technologies were able to achieve the GLI mercury target concentration at the bench-scale, albeit with different efficiencies and engineering implications. These results demonstrate that at this scale there is no fundamental physical or chemical barrier to achieving < 1.3 ng Hg/L in the tested wastewater. The study also found that some technologies were effective on particulate mercury whereas others were effective on dissolved mercury. One emerging treatment technology was found to be effective on both particulate and dissolved mercury. Three mercury-removal technologies--ultrafiltration (particulate mercury), adsorption (dissolved mercury), and an emerging reactive filtration technology (particulate and dissolved mercury)--are recommended for further study. This research offers treatment alternatives for different forms of mercury in an oil refinery wastewater, which might be applicable to other types of mercury-containing wastewater.

Meeting world's most stringent Hg criterion: a pilot-study for the treatment of oil refinery wastewater using an ultrafiltration membrane process.

A membrane ultrafiltration (UF) technology was tested using an oil refinery's end-of-pipe effluent to demonstrate the proof of concept, i.e. can the Great Lakes Initiative criterion of less than 1.3 ppt be consistently met at the pilot-scale, and to provide the data necessary for preliminary full-scale process design. This study presents the successful pilot test conducted with continuous but varying feed conditions over a protracted period. The UF membrane process consistently provided a constant permeate quality at all tested operating conditions, virtually independent of the feed water characteristics and the feed Hg concentration (0.5-22.7 ppt). The treatment target of less than 1.3 ppt of Hg was met and exceeded for all tested conditions during the pilot study. Turbidity measurements were <0.5 NTU (with a MDL of 0.5 NTU) 85% of the time and <0.16 NTU 95% of the time when analyzed on-line. The TMP values were below the specification of (negative) 7-12 psi at all tested conditions during the pilot-study. Weekly maintenance cleans and monthly clean in place (CIP) events were very effective in consistently restoring the membrane permeability during the pilot-study.

Insights into Candida tropicalis nosocomial infections and virulence factors.

Candida tropicalis is considered the first or the second non-Candida albicans Candida (NCAC) species most frequently isolated from candidosis, mainly in patients admitted in intensive care units (ICUs), especially with cancer, requiring prolonged catheterization, or receiving broad-spectrum antibiotics. The proportion of candiduria and candidemia caused by C. tropicalis varies widely with geographical area and patient group. Actually, in certain countries, C. tropicalis is more prevalent, even compared with C. albicans or other NCAC species. Although prophylactic treatments with fluconazole cause a decrease in the frequency of candidosis caused by C. tropicalis, it is increasingly showing a moderate level of fluconazole resistance. The propensity of C. tropicalis for dissemination and the high mortality associated with its infections might be strongly related to the potential of virulence factors exhibited by this species, such as adhesion to different host surfaces, biofilm formation, infection and dissemination, and enzymes secretion. Therefore, the aim of this review is to outline the present knowledge on all the above-mentioned C. tropicalis virulence traits.

Silver nanoparticles: influence of stabilizing agent and diameter on antifungal activity against Candida albicans and Candida glabrata biofilms.

AIM: The purpose of this work was to evaluate the size-dependent antifungal activity of different silver nanoparticles (SN) colloidal suspensions against Candida albicans and Candida glabrata mature biofilms. METHODS AND RESULTS: The research presented herein used SN of three different average sizes (5, 10 and 60 nm), which were synthesized by the reduction of silver nitrate through sodium citrate and which were stabilized with ammonia or polyvinylpyrrolidone. Minimal inhibitory concentration (MIC) assays were performed using the microdilution methodology. The antibiofilm activity of SN was determined by total biomass quantification (by crystal violet staining) and colony forming units enumeration. MIC results showed that all SN colloidal suspensions were fungicidal against the tested strains at very low concentrations (0·4-3·3 µg ml(-1) ). With regard to biomass quantification, SN colloidal suspensions were very effective only against C. glabrata biofilms, achieving biomass reductions around 90% at a silver concentration of 108 µg ml(-1) . In general, all SN suspensions promoted significant log(10) reduction of the mean number of cultivable biofilm cells after exposure to silver concentrations at or higher than 108 µg ml(-1) . Moreover, the results showed that the particle size and the type of stabilizing agent used did not interfere in the antifungal activity of SN against Candida biofilms. CONCLUSIONS: This study suggests that SN have antifungal therapeutic potential, but further studies are still required namely regarding formulation and delivery means. SIGNIFICANCE AND IMPACT OF THE STUDY: SN may contribute to the development of new strategies for the improvement of oral health and quality of life particularly of the complete denture wearers.

A congenital tympanic membrane cholesteatoma (CTMC) in the adult: a case report.

OBJECTIVE: We present an additional very rare case of a congenital tympanic membrane cholesteatoma (CTMC) in the adult. METHOD: Case report and literature review of CTMC. CASE REPORT: A 54-year old man was referred to us by his primary care physician who noted a white mass on the right tympanic membrane without prior history of otorrhea, tympanic perforations or previous otologic procedures. The pearl was about 5 mm diameter, centered on the umbo of a normal tympanic membrane (TM). The audiogram and the tympanogram was absolutely normal. CT confirmed a soft round shape tissue mass, located in the centre of the TM near umbo. The mass protruded both in the auditory canal and in the middle ear space, touching the malleus extremity, without any relationship with medial wall of the cavum tympani. A surgical excision was performed using a "minimal" retroauricolar transcanalar approach: the CTMC was located into the thickness of the TM, between epidermic and mucous layers. The ossicular chain was preserved intact. A partial myringoplasty (underlay technique) using a temporalis fascia graft was necessary. Histopathology confirmed a cystic cholesteatoma. After two months and one year follow-up, otoendoscopy showed a well-healed TM with a preserved normal audiogram and tympanogram. DISCUSSION: This exceptional (probably the first reported) case showed the possible localization of the CC in the TM, also in the adult. Criteria for classification of a TM cholesteatoma as congenital and possible pathogenetic mechanisms are discussed.

Improving data quality on low level mercury wastewater analysis.

In order to compare treatability test results evaluating low-level mercury (Hg) removal from oil refinery wastewater, improvements in Hg analytical methods were conducted at two US EPA certified analytical labs. The revisions in the analytical protocols improved Hg recoveries and hence enabled more reliable data interpretation and comparison for the specific wastewater tested. Nevertheless, significant differences between results from the two laboratories were identified in a split-sample experiment.

Comparative evaluation of As, Se and V removal technologies for the treatment of oil refinery wastewater.

In this study, a broad range of readily deployable metal removal technologies were tested on a US refinery's wastewater to determine vanadium, arsenic and selenium removal performance. The bench-scale treatability studies were designed and performed so that test conditions could be as uniform as possible given the different mechanisms of action and engineering applications of each technology. The experimental data show that both ferric precipitation and reactive filtration were able to remove As, Se and V more efficiently from the wastewater than other tested technologies. Additionally, granular ferric hydroxide (GFH) adsorption was also effective in both V and As removal. Although the thiol-SAMMS adsorbent was developed for mercury removal, it also demonstrated appreciable selenium removal. None of the tested membrane filtration technologies showed any significant metals removal. This was attributed to the dissolved form of the metals as well as the wastewater's fouling characteristics.

Preoperative diagnosis of THYR 3 versus follicular lesion: malignant postoperative ratio.

AIM: In the evaluation of nodular thyroid lesions, cytology is the main diagnostic instrument, associated with ultrasound examination. METHODS: We prospectively categorized into a dedicated database, 612 patients submitted to thyroidectomy from January 2009 to December 2011. We selected two groups of patients: the cases with "follicular lesions" and the cases classified as "THYR 3" using Bethesda Classification. RESULTS: Of 612 patients submitted to TT, in 68 cases, 8 males (M) and 60 females (F), we recorded a preoperative cytological diagnosis compatible with THYR 3 class. In 56 cases, 82.4% of the patients (5 M, 51 F), we performed a thyroidectomy with Conventional technique (CT) and in 12 cases, 12.6% of the patients (3M, 9F) with video-assisted technique (MIVAT). In 39 cases (57.1%) of the THYR 3 patients treated, a benign disease was found while in the other 29 cases (42.9%) a differentiated thyroid cancer (DTC) were found. In patients with nodules classified as "follicular proliferation", treated in the same period and by the same surgical team, we recorded 97 cases (79 F, 18 M). The patients were treated with TT in 72 cases, with MIVAT in 22 cases; in 3 cases we performed a HT with traditional technique. Adenomatous hyperplasia was found in 51; DTC was found in 21 cases and adenoma in 25 cases. The analysis of the incidence of benign versus malignant disease between the 2 groups showed a P<0.0001. CONCLUSION: In our experience, we recommend surgery, TT or HT, for THYR 3 nodules analyzed for the first time by FNAB with sonographic pattern suspicious for malignancy.

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.

Silver colloidal nanoparticles: antifungal effect against adhered cells and biofilms of Candida albicans and Candida glabrata.

The aim of this study was to evaluate the effect of silver nanoparticles (SN) against Candida albicans and Candida glabrata adhered cells and biofilms. SN (average diameter 5 nm) were synthesized by silver nitrate reduction with sodium citrate and stabilized with ammonia. Minimal inhibitory concentration (MIC) tests were performed for C. albicans (n = 2) and C. glabrata (n = 2) grown in suspension following the Clinical Laboratory Standards Institute microbroth dilution method. SN were applied to adhered cells (2 h) or biofilms (48 h) and after 24 h of contact their effect was assessed by enumeration of colony forming units (CFUs) and quantification of total biomass (by crystal violet staining). The MIC results showed that SN were fungicidal against all strains tested at very low concentrations (0.4-3.3 µg ml(-1)). Furthermore, SN were more effective in reducing biofilm biomass when applied to adhered cells (2 h) than to pre-formed biofilms (48 h), with the exception of C. glabrata ATCC, which in both cases showed a reduction ∼90%. Regarding cell viability, SN were highly effective on adhered C. glabrata and respective biofilms. On C. albicans the effect was not so evident but there was also a reduction in the number of viable biofilm cells. In summary, SN may have the potential to be an effective alternative to conventional antifungal agents for future therapies in Candida-associated denture stomatitis.

A novel framework to classify marginal land for sustainable biomass feedstock production.

To achieve food and energy security, sustainable bioenergy has become an important goal for many countries. The use of marginal lands to produce energy crops is one strategy for achieving this goal, but what is marginal land? Current definitions generally focus on a single criterion, primarily agroeconomic profitability. Herein, we present a framework that incorporates multiple criteria including profitability of current land use, soil health indicators (erosion, flooding, drainage, or high slopes), and environmental degradation resulting from contamination of surface water or groundwater resources. We tested this framework for classifying marginal land in the state of Nebraska and estimated the potential for using marginal land to produce biofuel crops. Our results indicate that approximately 1.6 million ha, or 4 million acres, of land (approximately 8% of total land area) could be classified as marginal on the basis of at least two criteria. Second-generation lignocellulosic bioenergy crops such as switchgrass ( Panicum virgatum L.), miscanthus (Miscanthus giganteus), native prairie grasses, and short-rotation woody crops could be grown on this land in redesigned landscapes that meet energy and environmental needs, without significant impacts on food or feed production. Calculating tradeoffs between the economics of redesigned landscapes and current practices at the field scale is the next step for determining functional designs for integrating biofuel feedstock production into current land management practices.