A comprehensive characterization of 3D printable poly ether ketone ketone.

The current work focuses on the comprehensive characterization of a 3D printable biomaterial, polyether ketone ketone (PEKK). The PEKK granules are first characterized and then utilized for extrusion of the PEKK filaments. The extruded PEKK filaments are characterized for crystallinity, quality, and printability, wherein they exhibit amorphous nature, good quality, and appropriate printability. Utilizing the filaments, the samples are printed with the appropriate printing parameters, which are further characterized for layer adhesion, voids, and crystallinity, wherein they showed seamless layer adhesion, improper beads consolidation, and the amorphous nature. The as printed samples are further annealed at different temperatures (200 and 250 °C). The scanning electron microscopy (SEM) of the annealed samples (A-200 and A-250) revealed better void consolidation, while the X-ray diffraction (XRD) revealed better crystallinity compared to the un-annealed sample. The printed samples are also investigated for dynamic mechanical analysis (DMA), shape memory, and tensile properties. The storage moduli of the annealed samples are observed to be better than the un-annealed sample. The annealed samples exhibited better shape memory properties: shape fixity and shape recovery ratio of A-200 and A-250 samples, 90.28 and 90.75%, and 99.16 and 94.73%, respectively, compared to the un-annealed samples. The highest shape fixity ratio and the shape recovery ratio are noted for A-250 (90.75%) and A-200 (∼ 100%). The A-200 and A-250 samples showed enhanced tensile modulus and strength, 4.16 and 49.67%, and 36.61 and 35.06%, respectively compared to the un-annealed sample. The highest modulus is noted for A-250, while the strength is comparable (36.61 and 35.06%) for A-200 and A-250.

A radiologist's guide to median sternotomy.

Median sternotomy is widely recognised as the primary incision technique in cardiac surgery. This surgical procedure involves dividing the sternum to gain access to the heart and lungs, making it invaluable in correcting congenital heart defects. Furthermore, it is frequently employed in adult patients, particularly during coronary artery bypass graft (CABG) procedures. In this imaging review, we present a comprehensive overview of the pre-procedural assessment and various post-sternotomy complications encountered within our clinical experience at a tertiary cardiothoracic centre. The focus of this review is to outline the imaging features associated with mediastinal adhesions and establish the minimal safe distance between the sternum and common mediastinal structures when considering re-sternotomy. By providing visual examples, we aim to facilitate a better understanding of these key concepts. Moreover, we delve into a detailed discussion of a spectrum of postoperative complications that may arise following median sternotomy including those related to metalwork (sternal wire fracture), bone (sternal dehiscence, non-union and osteomyelitis), and soft tissue (abscess, haematoma).

HLA class II immunogenic mutation burden predicts response to immune checkpoint blockade.

BACKGROUND: Whereas human leukocyte antigen (HLA) class I mutation-associated neoantigen burden has been linked with response to immune checkpoint blockade (ICB), the role of HLA class II-restricted neoantigens in clinical responses to ICB is less studied. We used computational approaches to assess HLA class II immunogenic mutation (IMM) burden in patients with melanoma and lung cancer treated with ICB. PATIENTS AND METHODS: We analyzed whole-exome sequence data from four cohorts of ICB-treated patients with melanoma (n = 110) and non-small-cell lung cancer (NSCLC) (n = 123). MHCnuggets, a neural network-based model, was applied to estimate HLA class II IMM burdens and cellular fractions of IMMs were calculated to assess mutation clonality. We evaluated the combined impact of HLA class II germline genetic variation and class II IMM burden on clinical outcomes. Correlations between HLA class II IMM burden and density of tumor-infiltrating lymphocytes were computed from expression data. RESULTS: Responding tumors harbored a significantly higher HLA class II IMM burden for both melanoma and NSCLC (P ≤ 9.6e-3). HLA class II IMM burden was correlated with longer survival, particularly in the NSCLC cohort and in the context of low intratumoral IMM heterogeneity (P < 0.001). HLA class I and II IMM landscapes were largely distinct suggesting a complementary role for class II IMMs in tumor rejection. A higher HLA class II IMM burden was associated with CD4+ T-cell infiltration and programmed death-ligand 1 expression. Transcriptomic analyses revealed an inflamed tumor microenvironment for tumors harboring a high HLA class II IMM burden. CONCLUSIONS: HLA class II IMM burden identified patients with NSCLC and melanoma that attained longer survival after ICB treatment. Our findings suggest that HLA class II IMMs may impact responses to ICB in a manner that is distinct and complementary to HLA class I-mediated responses.

Extremely long-range, high-temperature Josephson coupling across a half-metallic ferromagnet.

The Josephson effect results from the coupling of two superconductors across a spacer such as an insulator, a normal metal or a ferromagnet to yield a phase coherent quantum state. However, in junctions with ferromagnetic spacers, very long-range Josephson effects have remained elusive. Here we demonstrate extremely long-range (micrometric) high-temperature (tens of kelvins) Josephson coupling across the half-metallic manganite La0.7Sr0.3MnO3 combined with the superconducting cuprate YBa2Cu3O7. These planar junctions, in addition to large critical currents, display the hallmarks of Josephson physics, such as critical current oscillations driven by magnetic flux quantization and quantum phase locking effects under microwave excitation (Shapiro steps). The latter display an anomalous doubling of the Josephson frequency predicted by several theories. In addition to its fundamental interest, the marriage between high-temperature, dissipationless quantum coherent transport and full spin polarization brings opportunities for the practical realization of superconducting spintronics, and opens new perspectives for quantum computing.

Morphological and genetic variation in populations of Sitana/ marudhamneydhal/ and the validity of Sitana attenboroughii/.

Dewlap morphology and body ratios are two of the main morphological characters used in delimiting Sitana spp. It becomes a statistical limitation when small samples are used in species descriptions, as outliers can be picked to be described as a distinct species. Genetic data has been used to support the distinctness of a species in Sitana. However, species with shallow genetic divergence becomes a problem if not thoroughly examined. We examine and report our findings on morphological and genetic differences in two populations of Sitana marudhamneydhal and one population of S. attenboroughii. The shallow genetic divergence and overlapping morphology shows that Sitana attenboroughii is a junior synonym of Sitana marudhamneydhal.

Mycobacterium tuberculosis CysA2 is a dual sulfurtransferase with activity against thiosulfate and 3-mercaptopyruvate and interacts with mammalian cells.

Cyanide is a toxic compound that is converted to the non-toxic thiocyanate by a rhodanese enzyme. Rhodaneses belong to the family of transferases (sulfurtransferases), which are largely studied. The sulfur donor defines the subfamily of these enzymes as thiosulfate:cyanide sulfurtransferases or rhodaneses (TSTs) or 3-mercaptopyruvate sulfurtransfeases (MSTs). In Mycobacterium tuberculosis, the causative agent of tuberculosis, the gene Rv0815c encodes the protein CysA2, a putative uncharacterized thiosulfate:cyanide sulfurtransferase that belongs to the essential sulfur assimilation pathway in the bacillus and is secreted during infection. In this work, we characterized the functional and structural properties of CysA2 and its kinetic parameters. The recombinant CysA2 is a α/ß protein with two rhodanese-like domains that maintains the functional motifs and a catalytic cysteine. Sulfurtransferase activity was determined using thiosulfate and 3-mercaptopyruvate as sulfur donors. The assays showed Km values of 2.89 mM and 7.02 mM for thiosulfate and 3-mercaptopyruvate, respectively, indicating the protein has dual activity as TST and MST. Immunological assays revealed that CysA2 interacted with pulmonary cells, and it was capable to activate macrophages and dendritic cells, indicating the stimulation of the immune response, which is important for its use as an antigen for vaccine development and immunodiagnostic.

The development of pulmonary aspergillosis and its histologic, clinical, and radiologic manifestations.

Pulmonary syndromes following exposure to Aspergillus sp. have a variety of clinical and radiological manifestations. The radiological manifestations mirror the pathophysiological response to Aspergillus sp., which is linked closely to the patient's immune status. The plethora of terms in the literature can be confusing and their application with relevance to radiological imaging may subsequently result in inadequate or non-specific classification. In this review, we aim to provide a simplified and up-to-date approach to the recognition of the imaging manifestations of pulmonary aspergillosis, using correlation with histopathological and clinical descriptors. This will enable the radiologist to utilise the imaging findings to instigate clinically useful and appropriate management for those patients at risk of significant morbidity and mortality.

An experimental assessment on the performance of different lubrication techniques in grinding of Inconel 751.

The application of emulsion for combined heat extraction and lubrication requires continuous monitoring of the quality of emulsion to sustain a desired grinding environment; this is applicable to other grinding fluids as well. Thus to sustain a controlled grinding environment, it is necessary to adopt an effectively lubricated wheel-work interface. The current study was undertaken to assess experimentally the ​ effects of different grinding environments such as dry, minimum quantity lubrication (MQL) and Cryo-MQL on performance, such as grinding force, temperature, surface roughness and chip morphology on Inconel 751, a higher heat resistance material posing thermal problems and wheel loading. The results show that grinding with the combination of both liquid nitrogen (LN2) and MQL lowers temperature, cutting forces, and surface roughness as compared with MQL and dry grinding. Specific cutting energy is widely used as an inverse measure of process efficiency in machining. It is found from the results that specific cutting energy of Cryo-MQL assisted grinding is 50-65% lower than conventional dry grinding. The grindability of Inconel 751 superalloy can be enhanced with Cryo-MQL condition.

Sublingual immunization with the phosphate-binding-protein (PstS) reduces oral colonization by Streptococcus mutans.

Bacterial ATP-binding cassette (ABC) transporters play a crucial role in the physiology and pathogenicity of different bacterial species. Components of ABC transporters have also been tested as target antigens for the development of vaccines against different bacterial species, such as those belonging to the Streptococcus genus. Streptococcus mutans is the etiological agent of dental caries, and previous studies have demonstrated that deletion of the gene encoding PstS, the substrate-binding component of the phosphate uptake system (Pst), reduced the adherence of the bacteria to abiotic surfaces. In the current study, we generated a recombinant form of the S. mutans PstS protein (rPstS) with preserved structural features, and we evaluated the induction of antibody responses in mice after sublingual mucosal immunization with a formulation containing the recombinant protein and an adjuvant derived from the heat-labile toxin from enterotoxigenic Escherichia coli strains. Mice immunized with rPstS exhibited systemic and secreted antibody responses, measured by the number of immunoglobulin A-secreting cells in draining lymph nodes. Serum antibodies raised in mice immunized with rPstS interfered with the adhesion of bacteria to the oral cavity of naive mice challenged with S. mutans. Similarly, mice actively immunized with rPstS were partially protected from oral colonization after challenge with the S. mutans NG8 strain. Therefore, our results indicate that S. mutans PstS is a potential target antigen capable of inducing specific and protective antibody responses after sublingual administration. Overall, these observations raise interesting perspectives for the development of vaccines to prevent dental caries.

[INDICATORS OF QUALITY OF ENDOSCOPY DEPARTMENTS (CABINET) ACTIVITIES].

The article presents the possible indicators of quality of endoscopy departments (cabinet) activities, developed on the basis of the experience of foreign colleagues using information resource: PubMed, Cochrane Library, MDConsult, DynaMed, Google Schola and search engine TRIP Database www.tripdatabase.com, existing regulations as well as their own experience.

Effect of substrate interface on the magnetism of supported iron nanoparticles.

In situ X-ray photo-emission electron microscopy is used to investigate the magnetic properties of iron nanoparticles deposited on different single crystalline substrates, including Si(001), Cu(001), W(110), and NiO(001). We find that, in our room temperature experiments, Fe nanoparticles deposited on Si(001) and Cu(001) show both superparamagnetic and magnetically stable (blocked) ferromagnetic states, while Fe nanoparticles deposited on W(110) and NiO(001) show only superparamagnetic behaviour. The dependence of the magnetic behaviour of the Fe nanoparticles on the contact surface is ascribed to the different interfacial bonding energies, higher for W and NiO, and to a possible relaxation of point defects within the core of the nanoparticles on these substrates, that have been suggested to stabilise the ferromagnetic state at room temperature when deposited on more inert surfaces such as Si and Cu.

Prognostic implication of the loss of TGFBR2 expression in oral carcinoma.

Oral squamous cell carcinoma (OSCC) is a disease that strikes many worldwide, accounting for more than 145,000 deaths annually. This study examined the role of Transforming Growth Factor Beta (TGFß) signalling alterations in oral carcinogenesis and also its influence on the disease prognosis. In presented study, we evaluated the protein-level alterations of core TGFß signalling members in 20 potentially malignant oral disorders (PMDs) - leukoplakia and submucous fibrosis and 87 oral cancer samples by western blotting. Further, we analysed the association between these alterations and prognosis of oral carcinoma. For statistical analyses, univariate test like Student's 't'-test to compare expression level of various genes and logrank test has been used to compare the Kaplan-Meier survival curves. The multivariate model such as Cox's proportional hazard regression was used to verify the independent influence of each variable on the survival endpoints. A gradual decrease in the expression of TGFß signalling members like SMAD2, SMAD4, TGFBR1 and TGFBR2 have been noted from normal to PMD in oral cancers. The bio-activeforms, SMAD2/3 also showed a similar trend. SMAD3 protein was downregulated significantly in the PMD stage itself. Thus an inverse correlation was observed between expression of TGFß members and oral cancer progression.Furthermore, oral cancer patients showing TGFBR2 downregulation exhibited poor disease-free survival (p=0.005) and poor overall survival (p=0.012).Thus, assessing the TGFBR2 protein levels can serve as one of the prognostic marker for oral cancer.

The evolving role of MDCT in the assessment of patients with chronic obstructive pulmonary disease.

The purpose of this article is to educate the reader in the value a radiologist can offer in the multidetector (MD) CT assessment of patients with chronic obstructive pulmonary disease (COPD). MDCT can identify patients in whom treatments such as lung volume reduction surgery or newer endobronchial therapies may be of benefit. We will also discuss important and under-recognised associated cardiorespiratory disease, which may be incidentally identified.

Prognostic implication of the loss of TGFBR2 expression in oral carcinoma.

Oral squamous cell carcinoma (OSCC) is a disease that strikes many worldwide, accounting for more than 145,000 deaths annually. This study examined the role of Transforming Growth Factor Beta (TGFß) signalling alterations in oral carcinogenesis and also its influence on the disease prognosis. In presented study, we evaluated the protein-level alterations of core TGFß signalling members in 20 potentially malignant oral disorders (PMDs) - leukoplakia and submucous fibrosis and 87 oral cancer samples by western blotting. Further, we analysed the association between these alterations and prognosis of oral carcinoma. For statistical analyses, univariate test like Student's 't'-test to compare expression level of various genes and logrank test has been used to compare the Kaplan-Meier survival curves. The multivariate model such as Cox's proportional hazard regression was used to verify the independent influence of each variable on the survival endpoints. A gradual decrease in the expression of TGFß signalling members like SMAD2, SMAD4, TGFBR1 and TGFBR2 have been noted from normal to PMD in oral cancers. The bio-activeforms, SMAD2/3 also showed a similar trend. SMAD3 protein was downregulated significantly in the PMD stage itself. Thus an inverse correlation was observed between expression of TGFß members and oral cancer progression.Furthermore, oral cancer patients showing TGFBR2 downregulation exhibited poor disease-free survival (p=0.005) and poor overall survival (p=0.012).Thus, assessing the TGFBR2 protein levels can serve as one of the prognostic marker for oral cancer.

Micafungin twice weekly as antifungal prophylaxis in paediatric patients at high risk for invasive fungal disease.

BACKGROUND: Current guidelines recommend antifungal prophylaxis for children at high risk for invasive fungal disease (IFD), but the use of polyenes and triazoles may not be feasible in some patients due to toxicities and drug-drug interactions. Micafungin is well tolerated, with intravenous daily dosing being the current standard. Recent reports indicate safety and efficacy of intermittent dosing of micafungin. METHODS: We analysed safety, efficacy and micafungin serum concentrations of children at high risk for IFD receiving prophylactic micafungin between 3 and 4 mg/kg twice weekly. All children were intolerant or had contraindications to polyenes and triazoles. RESULTS: A total of 21 children (median age = 9 years) at high risk for IFD were included in the analysis. No significant clinical adverse event occurred, and end of treatment values of parameters of renal and hepatic function in serum were not different from baseline. Proven or probable breakthrough IFD did not occur in any of the patients. In 9 out of 11 patients in whom plasma micafungin concentrations were assessed, the first trough concentration exceeded 150 ng/mL, a concentration proposed to be effective for prophylaxis. CONCLUSIONS: Our data indicate that micafungin administered twice weekly at a dosage of 3-4 mg/kg of bodyweight could be a convenient, safe and efficient alternative for antifungal prophylaxis in children at high risk for IFD.

Multidetector CT of pulmonary cavitation: filling in the holes.

Pulmonary cavitation causes significant morbidity and mortality. Early diagnosis of the presence and aetiology of a cavity is therefore crucial in order to avoid further demise in both the localized pulmonary and systemic disorders that may manifest with pulmonary cavity formation. Multidetector CT has become the principal diagnostic technique for detecting pulmonary cavitation and its complications. This review provides an overview of the aetiologies and their imaging findings using this technique. Combining a literature review with case illustration, a synopsis of the different imaging features and constellations is provided, which may suggest a particular cause and aid the differentiation from diseases with similar findings.

Methylphenidate and desipramine combined treatment improves PTSD symptomatology in a rat model.

Antidepressant medication constitutes the first line pharmacological treatment for posttraumatic stress disorder (PTSD), however, because many patients display no beneficial drug effects it has been suggested that combinations of antidepressants with additional drugs may be necessary. The defining symptoms of PTSD include re-experiencing, avoidance and hyperarousal. In addition, PTSD patients were shown to become easily distracted and often suffer from poor concentration together with indications of comorbidity with attention-deficit hyperactivity disorder (ADHD). Methylphenidate (MPH) is the most common and effective drug treatment for ADHD, thus we aimed to investigate the effects of MPH treatment, by itself or in combination with the antidepressants fluoxetine (FLU) or desipramine (DES). We modified an animal model of PTSD by exposing rats to chronic stress and evaluating the subsequent development of behavioral PTSD-like symptoms, as well as the effects on proinflammatory cytokines, which were implicated in PTSD. We report that while FLU or DES had a beneficial effect on avoidance and hyperarousal symptoms, MPH improved all three symptoms. Moreover, the combination of MPH with DES produced the most dramatic beneficial effects. Serum levels of interleukin-1ß (IL-1ß) and IL-6 were elevated in the PTSD-like group compared with the control group, and were decreased by MPH, FLU, DES or the combination drug treatments, with the combination of DES+MPH producing the most complete rescue of the inflammatory response. Considering the versatile symptoms of PTSD, our results suggest a new combined treatment for PTSD comprising the antidepressant DES and the psychostimulant MPH.

In situ magnetic and electronic investigation of the early stage oxidation of Fe nanoparticles using X-ray photo-emission electron microscopy.

We present an in situ experimental investigation of the magnetic and electronic properties of individual iron nanoparticles with sizes ranging from 8 to 22 nm as a function of oxygen exposure (0-80 L), using X-ray photoemission electron microscopy. The X-ray absorption spectroscopy results show that, irrespective of size and magnetic state, the early stages of the Fe nanoparticle oxidation occur through the initial formation of a non-magnetic FeO-like layer, followed by a progressive transformation of the latter to Fe3O4. At 80 L, the metallic iron core and the outer Fe3O4 shell are separated by a thin FeO layer. Our data suggest that the outer Fe3O4 layer has either a magnetic order that significantly differs from the respective bulk or that the FeO-like layer is responsible for a magnetic decoupling between the Fe3O4 shell and the iron core. Moreover, we find that the recently observed blocked magnetic state in the pure metallic iron nanoparticles persists upon oxygen exposure, demonstrating that the enhanced magnetic energy barriers do not originate from the free surface of the nanoparticles.

Mesenchymal stromal cells in the antimicrobial host response of hematopoietic stem cell recipients with graft-versus-host disease--friends or foes?

Mesenchymal stromal cells (MSCs) are multipotent cells, which exhibit broad immunosuppressive activities. Moreover, they may be administered irrespectively of human leukocyte antigen (HLA) compatibility, without inducing life-threatening immunological reactions, as they express no HLA class II and limited HLA class I antigens under resting conditions. These characteristics have made MSC an appealing candidate for cell therapy after hematopoietic stem cell transplantation (HSCT), for example, for treatment of graft-versus-host disease (GvHD) or for graft rejection prevention/treatment in allogeneic HSCT recipients. Unfortunately, information regarding the effect of MSC infusion on the host response to infectious agents is scarce, and study results on infectious complications in patients receiving MSC are conflicting. The present review focuses on the available data from in vitro studies and animal models regarding the interaction of MSC with bacterial, viral and fungal pathogens. In a clinical part, we present the current information on infectious complications in allogeneic HSCT recipients who had received MSCs as prophylaxis or treatment of GvHD disease.