Tuning Catalyst Selectivity for Ammonia vs Hydrogen: An Investigation into the Coprecipitation of Mo and Fe Sulfides.

Iron sulfides are key materials in metalloprotein catalysis. One interesting aspect of iron sulfides in biology is the incorporation of secondary metals, for example, Mo, in nitrogenase. These secondary metals may provide vital clues as to how these enzymes first emerged in nature. In this work, we examined the materials resulting from the coprecipitation of molybdenum with iron sulfides using X-ray absorption spectroscopy (XAS). The materials were tested as catalysts, and direct reductants using nitrite (NO2-) and protons (H+) as test substrates. It was found that Mo will coprecipitate with iron as sulfides, however, in distinct ways depending on the stoichiometric ratios of Mo, Fe, and HS-. It was observed that the selectivity of reduction products depends on the amount of molybdenum, with the presence of approximately at 10% Mo optimizing ammonium/ammonia (NH4+/NH3) production from NO2- and minimizing competitive hydrogen (H2) formation from protons (H+) with a secondary reductant.

Localization Techniques for Non-Palpable Breast Lesions: Current Status, Knowledge Gaps, and Rationale for the MELODY Study (EUBREAST-4/iBRA-NET, NCT 05559411).

BACKGROUND: Surgical excision of a non-palpable breast lesion requires a localization step. Among available techniques, wire-guided localization (WGL) is most commonly used. Other techniques (radioactive, magnetic, radar or radiofrequency-based, and intraoperative ultrasound) have been developed in the last two decades with the aim of improving outcomes and logistics. METHODS: We performed a systematic review on localization techniques for non-palpable breast cancer. RESULTS: For most techniques, oncological outcomes such as lesion identification and clear margin rate seem either comparable with or better than for WGL, but evidence is limited to small cohort studies for some of the devices. Intraoperative ultrasound is associated with significantly higher negative margin rates in meta-analyses of randomized clinical trials (RCTs). Radioactive techniques were studied in several RCTs and are non-inferior to WGL. Smaller studies show higher patient preference towards wire-free localization, but little is known about surgeons' and radiologists' attitudes towards these techniques. CONCLUSIONS: Large studies with an additional focus on patient, surgeon, and radiologist preference are necessary. This review aims to present the rationale for the MELODY (NCT05559411) study and to enable standardization of outcome measures for future studies.

Focused investigations to expedite cancer diagnosis among patients with lymphadenopathy in a tuberculosis and HIV-endemic region.

PURPOSE: In tuberculosis (TB)-endemic areas, lymphadenopathy is frequently due to TB adenitis, but lymphoma and cancers are important differential diagnoses and critical to diagnose at the earliest opportunity. Key obstacles to lymphoma diagnosis include empiric TB treatment and difficulty accessing a biopsy. We report on a specialized clinic utilizing high-yield investigations for patients with lymphadenopathy. METHODS: This prospective interventional study investigated the utility of a core biopsy and the Xpert MTB/RIF Ultra (Ultra) on fine-needle aspirate (FNA) and tissue in a newly established lymph node biopsy clinic over 4 years. Electronic referral facilitated patient assessment within a week. Hematology fellows without specialist surgical or radiological expertise performed the biopsy on the first visit. RESULTS: In 277 patients, including 43% people with HIV, TB was the most frequent diagnosis (34%), followed by lymphoma (27%) and other cancers (17%). Patients were seen a median of 5 days [interquartile range (IQR) 2-8.5 days] from referral. Core biopsy provided sufficient tissue for diagnosis in 96% of patients with lymphoma (72/75) and 94% of patients with cancer (44/47). FNA Ultra had a sensitivity of 73.9% [34/46; 95% confidence interval (CI) 58.9-85.7], and tissue Ultra 73% (46/63; 95% CI 60.3-83.4). There were six false-positive Ultra tests, highlighting the value of histology to either support TB or make an alternative diagnosis. CONCLUSION: Core biopsies collected under the conditions described are safe and sensitive and can yield a rapid diagnosis. Combining Ultra and a core biopsy can accurately diagnose TB and cancer. This clinic provides an implementation model for resource-constrained and TB-endemic areas.

Palpable breast lumps: An age-based approach to evaluation and diagnosis.

A palpable breast lump is a common presentation of breast disease to a general practitioner. Fortunately, investigation of most of these lumps will lead to a benign diagnosis. It is essential to have a clear and systematic approach when investigating a palpable breast lump to avoid over investigation with the resultant increase in healthcare cost and anxiety. This article will discuss an approach to evaluating and diagnosing a palpable breast lump in the primary care setting.

Palpable breast lumps an age-based approach to evaluation and diagnosis

A palpable breast lump is a common presentation of breast disease to a general practitioner. Fortunately, investigation of most of these lumps will lead to a benign diagnosis. It is essential to have a clear and systematic approach when investigating a palpable breast lump to avoid over investigation with the resultant increase in healthcare cost and anxiety. This article will discuss an approach to evaluating and diagnosing a palpable breast lump in the primary care setting

Correction to: Diagnostic accuracy of the Xpert MTB/Rif Ultra for tuberculosis adenitis.

After publication of the original article [1], we were notified that there is a mistake in the article note.

Diagnostic accuracy of the Xpert MTB/Rif Ultra for tuberculosis adenitis.

BACKGROUND: The WHO recently recommended the new Xpert MTB/RIF Ultra assay (Ultra) instead of the Xpert MTB/RIF assay because Ultra has improved sensitivity. We report the diagnostic accuracy of Ultra for tuberculous adenitis in a tuberculosis and HIV endemic setting. METHODS: We obtained fine-needle aspirates (FNA) and lymph node tissue by core-needle biopsy in adult patients with peripheral lymphadenopathy of >20 mm. Ultra and mycobacterial culture were performed on FNA and tissue specimens, with histological examination of tissue specimens. We assessed the diagnostic accuracy of Ultra against a composite reference standard of 'definite tuberculosis' (microbiological criteria) or 'probable tuberculosis' (histological and clinical criteria). RESULTS: We prospectively evaluated 99 participants of whom 50 were HIV positive: 21 had 'definite tuberculosis', 15 'probable tuberculosis' and 63 did not have tuberculosis (of whom 38% had lymphoma and 19% disseminated malignancy). Using the composite reference standard the Ultra sensitivity on FNA was 70% (95% CI 51-85; 21 of 30), and on tissue was 67% (45-84; 16/24) these were far superior to the detection of acid-fast bacilli on an FNA (26%; 7/27); AFB on tissue (33%; 8/24); or tissue culture (39%; 9/23). The detection of granulomas on histology had high senstivity (83%) but the lowest specficity. When compared with culture the Ultra on FNA had a sensitvity of 78% (40-97; 7/9) and tissue 90% (55-100; 9/10). CONCLUSIONS: Ultra performed on FNA or tissue of a lymph node had good sensitivity and high specificity. Ultra had a higher yield than culture and has the advantage of being a rapid test. Ultra on FNA would be an appropriate initial investigation for lymphadenopathy in tuberculosis endemic areas followed by a core biopsy for histopathology with a repeat Ultra on tissue if granulomas are present.

An autologous dendritic cell vaccine polarizes a Th-1 response which is tumoricidal to patient-derived breast cancer cells.

Breast cancer remains one of the leading causes of cancer-associated death worldwide. Conventional treatment is associated with substantial toxicity and suboptimal efficacy. We, therefore, developed and evaluated the in vitro efficacy of an autologous dendritic cell (DC) vaccine to treat breast cancer. We recruited 12 female patients with stage 1, 2, or 3 breast cancer and matured their DCs with autologous tumour-specific lysate, a toll-like receptor (TLR)-3 and 7/8 agonist, and an interferon-containing cocktail. The efficacy of the vaccine was evaluated by its ability to elicit a cytotoxic T-lymphocyte response to autologous breast cancer cells in vitro. Matured DCs (≥ 60% upregulation of CD80, CD86, CD83, and CCR7) produced high levels of the Th1 effector cytokine, IL12-p70 (1.2 ng/ml; p < 0.0001), compared to DCs pulsed with tumour lysate, or matured with an interferon-containing cocktail alone. We further showed that matured DCs enhance antigen-specific CD8 + T-cell responses to HER-2 (4.5%; p < 0.005) and MUC-1 (19%; p < 0.05) tetramers. The mature DCs could elicit a robust and dose-dependent antigen-specific cytotoxic T-lymphocyte response (65%) which was tumoricidal to autologous breast cancer cells in vitro compared to T-lymphocytes that were primed with autologous lysate loaded-DCs (p < 0.005). Lastly, we showed that the mature DCs post-cryopreservation maintained high viability, maintained their mature phenotype, and remained free of endotoxins or mycoplasma. We have developed a DC vaccine that is cytotoxic to autologous breast cancer cells in vitro. The tools and technology generated here will now be applied to a phase I/IIa clinical trial.

Debundling, Dispersion, and Stability of Multiwalled Carbon Nanotubes Driven by Molecularly Designed Electron Acceptors.

Carbon nanotubes (CNTs) have attracted significant attention because of their outstanding physical and chemical properties, and yet, their high natural tendency to form bundles, ropes, or aggregates, as a consequence of their strong π-π interactions, limits their solvent processing and further applications. Efficient processing solvents, mostly amide-based, that partially compensate for these strong inter-CNT π-π interactions have been widely reported. However, the yield of debundled/dispersed CNTs and the stability of subsequent dispersions in these solvents remain key challenges. Moreover, there are major concerns related to the large-scale use of conventional solvents, as they are fossil fuel based and intrinsically highly toxic, hence the need to identify environmentally friendly and safer alternatives. Herein, we address these challenges by using a ternary system composed of multiwalled CNTs (MWCNTs), tailored electron-deficient acceptors, and an organic solvent. Not only do the electron-deficient acceptors interrupt the inter-CNTs π-π interactions, thereby enabling the subsequent debundling and dispersion of MWCNTs aggregates in the solvent, they also act as stabilizers, after dispersion, by inhibiting inter-CNT π-π interactions and re-agglomeration. The use of electron acceptors increases the yield by a factor of 165 in N-methyl 2-pyrrolidone, improves the long-term stability of the debundled and dispersed MWCNTs, and reduces the energy input to only 30 min of mild bath sonication, compared with prolonged high-energy sonication reported in the literature. We also report for the first time, the use in MWCNT processing of a "green" biosolvent, dihydrolevoglucosenone, as an environmentally friendly and nontoxic alternative to the more conventional amide-based solvents.

Defects regulating of graphene ink for electrochemical determination of ascorbic acid, dopamine and uric acid.

A simple water immersing treatment has been established for regulating the electrocatalytic activity of commercial graphene ink. This process enables to remove additives in graphene ink and consequently expose the surface defects. A graphene ink coated glass has been fabricated as an example platform for simultaneous determination of ascorbic acid (AA), dopamine (DA), and uric acid (UA). Cyclic voltammetry studied indicated electrocatalytic reaction can be initiated after the additives leaching during the water immersing treatment. Under optimal conditions, the linear calibration curves were achieved in the range of 50-1000, 3-140, and 0.5-150µM, with detection limits of 17.8, 1.44 and 0.29µM for AA, DA, and UA, respectively. This work demonstrated that the removal of additives of the graphene ink after film coating could be applied as a simple and cost-effective electrochemical platform for sensing application.

The Oxidation of Peroxide by Disordered Metal Oxides: A Measurement of Thermodynamic Stability "By Proxy".

It is often noted that disordered materials have different chemical properties to their more "ordered" cousins. Quantifying these effects in terms of thermodynamics is challenging in part because disordered materials can be difficult to characterise and are frequently relatively unstable. During the course of our experiments to understand the effects of disorder in catalysts for water oxidation we observed that many disordered manganese and cobalt oxide water oxidation catalysts directly oxidised peroxide in contrast to their more ordered analogues which catalysed its disproportionation, that is, MnO2 +2 H+ +H2 O2 →Mn2+ +2 H2 O+O2 (oxidation) versus H2 O2 →H2 O+ 1 / 2 O2 (disproportionation). By measuring the efficiency for one reaction over the other as a function of pH, we were able to quantify the relative stability of materials in two series of metal oxides and thereby quantify their relative thermodynamic stability, "by proxy". We found that for the series of catalysts investigated the disorder made the materials stronger chemical oxidants and worse catalysts for the disproportionation of peroxide.

High Modulus Biodegradable Polyurethanes for Vascular Stents: Evaluation of Accelerated in vitro Degradation and Cell Viability of Degradation Products.

We have recently reported the mechanical properties and hydrolytic degradation behavior of a series of NovoSorb™ biodegradable polyurethanes (PUs) prepared by varying the hard segment (HS) weight percentage from 60 to 100. In this study, the in vitro degradation behavior of these PUs with and without extracellular matrix (ECM) coating was investigated under accelerated hydrolytic degradation (phosphate buffer saline; PBS/70°C) conditions. The mass loss at different time intervals and the effect of aqueous degradation products on the viability and growth of human umbilical vein endothelial cells (HUVEC) were examined. The results showed that PUs with HS 80% and below completely disintegrated leaving no visual polymer residue at 18 weeks and the degradation medium turned acidic due to the accumulation of products from the soft segment (SS) degradation. As expected the PU with the lowest HS was the fastest to degrade. The accumulated degradation products, when tested undiluted, showed viability of about 40% for HUVEC cells. However, the viability was over 80% when the solution was diluted to 50% and below. The growth of HUVEC cells is similar to but not identical to that observed with tissue culture polystyrene standard (TCPS). The results from this in vitro study suggested that the PUs in the series degraded primarily due to the SS degradation and the cell viability of the accumulated acidic degradation products showed poor viability to HUVEC cells when tested undiluted, however particles released to the degradation medium showed cell viability over 80%.

Marinobacter salarius sp. nov. and Marinobacter similis sp. nov., isolated from sea water.

Two non-pigmented, motile, Gram-negative marine bacteria designated R9SW1T and A3d10T were isolated from sea water samples collected from Chazhma Bay, Gulf of Peter the Great, Sea of Japan, Pacific Ocean, Russia and St. Kilda Beach, Port Phillip Bay, the Tasman Sea, Pacific Ocean, respectively. Both organisms were found to grow between 4 °C and 40 °C, between pH 6 to 9, and are moderately halophilic, tolerating up to 20% (w/v) NaCl. Both strains were found to be able to degrade Tween 40 and 80, but only strain R9SW1T was found to be able to degrade starch. The major fatty acids were characteristic for the genus Marinobacter including C16:0, C16:1ω7c, C18:1ω9c and C18:1ω7c. The G+C content of the DNA for strains R9SW1T and A3d10T were determined to be 57.1 mol% and 57.6 mol%, respectively. The two new strains share 97.6% of their 16S rRNA gene sequences, with 82.3% similarity in the average nucleotide identity (ANI), 19.8% similarity in the in silico genome-to-genome distance (GGD), 68.1% similarity in the average amino acid identity (AAI) of all conserved protein-coding genes, and 31 of the Karlin's genomic signature dissimilarity. A phylogenetic analysis showed that R9SW1T clusters with M. algicola DG893T sharing 99.40%, and A3d10T clusters with M. sediminum R65T sharing 99.53% of 16S rRNA gene sequence similarities. The results of the genomic and polyphasic taxonomic study, including genomic, genetic, phenotypic, chemotaxonomic and phylogenetic analyses based on the 16S rRNA, gyrB and rpoD gene sequence similarities, the analysis of the protein profiles generated using MALDI-TOF mass spectrometry, and DNA-DNA relatedness data, indicated that strains R9SW1T and A3d10(T) represent two novel species of the genus Marinobacter. The names Marinobacter salarius sp. nov., with the type strain R9SW1(T) ( =  LMG 27497(T)  =  JCM 19399(T)  =  CIP 110588(T)  =  KMM 7502(T)) and Marinobacter similis sp. nov., with the type strain A3d10(T) ( =  JCM 19398(T)  =  CIP 110589(T)  =  KMM 7501T), are proposed.

Physicochemical characterization of solid lipid nanoparticles (SLNs) prepared by a novel microemulsion technique.

HYPOTHESIS: Solid lipid nanoparticles (SLNs) produced by conventional microemulsion techniques using thermal heat have specific limitations (e.g. high polydispersity, instability and low encapsulation). Replacing thermal heat with microwave heat may produce SLNs which overcome some of these limitations. EXPERIMENTS: Stearic acid-based SLNs prepared with Tween® 20 as the emulsifier were chosen as the optimum formulation to encapsulate and potentially deliver the antibacterial drug tetracycline. All formulations were characterized for their particle size, zeta potential, encapsulation efficiency, loading capacity, thermal and X-ray diffraction analyses. Short-term stability and in vitro drug studies were also performed. FINDINGS: Microwave heating helps to overcome several disadvantages associated with thermal heating (nonuniform, inefficient and slow) and results in improved particle characteristics. There is thus the potential for new opportunities in the development of colloidal carriers. The particle sizes of microwave-produced SLNs were in the desired nanometer range (200-250 nm) with both lower size and lower polydispersity than the conventional SLNs. We take this as an indication of improved stability; however zeta potential measurements were not different, indicating similar stability. True stability testing (visual observation with time) did show that the microwave-induced SLNs were found to be more stable, particularly when refrigerated. The microwave-produced SLNs also demonstrated improved encapsulation efficiency and loading capacity. Thermal and diffraction analysis confirmed a lowered crystallinity of stearic acid with successful incorporation of tetracycline into the SLNs. In vitro release studies indicated that, after an initial burst release, SLNs could provide prolonged release of tetracycline. The presence of tetracycline and non-toxicity of carriers towards microbes was confirmed by antimicrobial susceptibility tests.

Properties and in vitro evaluation of high modulus biodegradable polyurethanes for applications in cardiovascular stents.

This study examined the suitability of a family of biodegradable polyurethanes (PUs) NovoSorb developed for the vascular stent application. These segmented PUs are formulated to be biodegradable using degradable polyester and PU blocks. A series of PUs comprising different hard segment weight percentage ranging from 60 to 100 were investigated. The mechanical properties of the PUs were evaluated before and after gamma sterilization to assess their suitability for vascular implants. The real-time (PBS/37°C/pH 7.4) hydrolytic degradation studies were carried out under sterile conditions and PU glass transition temperature, molecular weight, and mass loss at 3, 6, and 9 months were determined. The viability and growth of Human Umbilical Vein Endothelial Cells (HUVEC) on PU surfaces were determined to assess the effect of PU degradation. The effect of coating of extracellular matrix (ECM) components on cell viability was also investigated. The study showed that the PUs possess excellent mechanical properties exhibiting high tensile strength (41-56 MPa) and tensile modulus (897-1496 MPa). The PU films maintained mechanical strength during the early phase of the degradation but lost strength at latter stages. The unmodified polymer surface of each PU promotes endothelial cell growth and proliferation, with a HUVEC retention rate of >70%.

Identification of traditional medicinal plant extracts with novel anti-influenza activity.

The emergence of drug resistant variants of the influenza virus has led to a need to identify novel and effective antiviral agents. As an alternative to synthetic drugs, the consolidation of empirical knowledge with ethnopharmacological evidence of medicinal plants offers a novel platform for the development of antiviral drugs. The aim of this study was to identify plant extracts with proven activity against the influenza virus. Extracts of fifty medicinal plants, originating from the tropical rainforests of Borneo used as herbal medicines by traditional healers to treat flu-like symptoms, were tested against the H1N1 and H3N1 subtypes of the virus. In the initial phase, in vitro micro-inhibition assays along with cytotoxicity screening were performed on MDCK cells. Most plant extracts were found to be minimally cytotoxic, indicating that the compounds linked to an ethnomedical framework were relatively innocuous, and eleven crude extracts exhibited viral inhibition against both the strains. All extracts inhibited the enzymatic activity of viral neuraminidase and four extracts were also shown to act through the hemagglutination inhibition (HI) pathway. Moreover, the samples that acted through both HI and neuraminidase inhibition (NI) evidenced more than 90% reduction in virus adsorption and penetration, thereby indicating potent action in the early stages of viral replication. Concurrent studies involving Receptor Destroying Enzyme treatments of HI extracts indicated the presence of sialic acid-like component(s) that could be responsible for hemagglutination inhibition. The manifestation of both modes of viral inhibition in a single extract suggests that there may be a synergistic effect implicating more than one active component. Overall, our results provide substantive support for the use of Borneo traditional plants as promising sources of novel anti-influenza drug candidates. Furthermore, the pathways involving inhibition of hemagglutination could be a solution to the global occurrence of viral strains resistant to neuraminidase drugs.

Updating the taxonomic toolbox: classification of Alteromonas spp. using multilocus phylogenetic analysis and MALDI-TOF mass spectrometry.

Bacteria of the genus Alteromonas are Gram-negative, strictly aerobic, motile, heterotrophic marine bacteria known for their versatile metabolic activities. Identification and classification of novel species belonging to the genus Alteromonas generally involves DNA-DNA hybridization (DDH) as distinct species often fail to be resolved at the 97 % threshold value of the 16S rRNA gene sequence similarity. In this study, the applicability of Multilocus Phylogenetic Analysis (MLPA) and Matrix-Assisted Laser Desorption Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF MS) for the differentiation of Alteromonas species has been evaluated. Phylogenetic analysis incorporating five house-keeping genes (dnaK, sucC, rpoB, gyrB, and rpoD) revealed a threshold value of 98.9 % that could be considered as the species cut-off value for the delineation of Alteromonas spp. MALDI-TOF MS data analysis reconfirmed the Alteromonas species clustering. MLPA and MALDI-TOF MS both generated data that were comparable to that of the 16S rRNA gene sequence analysis and may be considered as useful complementary techniques for the description of new Alteromonas species.

Collagen type I together with fibronectin provide a better support for endothelialization.

Endothelialization of vascular implants is limited by the inability of cells to retain adhesion when exposed to flow. Extracellular matrix proteins, including fibronectin and collagen, enhance cell adherence on materials. This study investigated the behaviour of Human Umbilical Vein Endothelial Cells (HUVEC) on extracellular matrix coated polystyrene. Collagen and fibronectin were coated as single and double layers to analyse differences in cell proliferation, morphology, and cell-protein interactions. Significantly higher endothelial cell proliferation and migration rates were observed on the collagen and collagen+fibronectin coating compared to the uncoated or fibronectin-coated sample. Immmunofluorescent microscopy showed evidence of extracellular matrix remodelling in the double, collagen+fibronectin coating. These results strongly suggest that a double coating of collagen+fibronectin provides a better support structure for endothelial cell growth and contributes to improve the ability of vascular implants to become and remain endothelialized.

Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus attachment patterns on glass surfaces with nanoscale roughness.

Attachment tendencies of Escherichia coli K12, Pseudomonas aeruginosa ATCC 9027, and Staphylococcus aureus CIP 68.5 onto glass surfaces of different degrees of nanometer-scale roughness have been studied. Contact-angle and surface-charge measurements, atomic force microscopy (AFM), scanning electron microscopy (SEM), and confocal laser scanning microscopy (CLSM) were employed to characterize substrata and bacterial surfaces. Modification of the glass surface resulted in nanometer-scale changes in the surface topography, whereas the physicochemical characteristics of the surfaces remained almost constant. AFM analysis indicated that the overall surface roughness parameters were reduced by 60-70%. SEM, CLSM, and AFM analysis clearly demonstrates that although E. coli, P. aeruginosa and S. aureus present significantly different patterns of attachment, all of the species exhibited a greater propensity for adhesion to the "nano-smooth" surface. The bacteria responded to the surface modification with a remarkable change in cellular metabolic activity, as shown by the characteristic cell morphologies, production of extracellular polymeric substances, and an increase in the number of bacterial cells undergoing attachment.