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.

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.

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.

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.

Atrial masses on multidetector computed tomography.

Incidental atrial filling defect on multidetector computed tomography (MDCT) is an important radiological finding, as irrespective of its nature, it may nevertheless be of considerable importance for correct diagnostic workup. MDCT is not the first-line imaging technique of choice for characterization of intra-atrial masses, but is a commonly performed examination and hence offers the opportunity to pick up hitherto unsuspected atrial lesions. This review highlights key CT imaging features that help to differentiate normal variants and artefacts from a true abnormality, distinguish benign from malignant intra-atrial tumours, and characterize non-neoplastic atrial masses.

Fibrous dysplasia--a 13-year retrospective radiographic analysis in a south Indian population.

OBJECTIVE: The aim of this study was to examine the clinical and radiographic presentation of fibrous dysplasia through a 13-year retrospective study in patients who reported to the outpatient unit of Government Dental College, Trivandrum. METHODS: The clinical file records and radiographs of the patients who reported to the outpatient clinic in the Department of Oral Medicine and Radiology were retrospectively reviewed for histopathologically diagnosed fibrous dysplasia. A detailed analysis of the clinical and radiographic features of the 24 cases retrieved was carried out. RESULTS: The male-to-female ratio of incidence was approximately 1:1. Most of the patients were in the second or third decade of life. Almost all the patients presented with a complaint of swelling on the side of the face. The mandible was more frequently involved than the maxilla. The most common radiographic pattern observed was the "ground-glass" appearance. Most of the patients exhibited expansion of the involved bone and loss of lamina dura of associated teeth. CONCLUSION: The awareness of protean features of fibrous dysplasia evident through this study is essential in the accurate diagnosis and proper treatment planning of such lesions.

Multi-technique imaging of sarcoidosis.

Sarcoidosis is a multisystem granulomatous disorder of unknown aetiology. The diagnosis is suggested on the basis of wide ranging clinical and radiological manifestations, and is supported by the histological demonstration of non-caseating granulomas in affected tissues. This review highlights the multisystem radiological features of the disease across a variety of imaging methods including multidetector computed tomography (CT), magnetic resonance imaging (MRI) as well as functional radionuclide techniques, particularly 2-[(18)F]-fluoro-2-deoxy-d-glucose (FDG) positron emission tomography/computed tomography (PET/CT). It is important for the radiologist to be aware of the varied radiological manifestations of sarcoidosis in order to recognize and suggest the diagnosis in the appropriate clinical setting.

Impact of the introduction of integrated PET-CT into the preoperative staging pathway of patients with potentially operable oesophageal carcinoma.

AIM: To retrospectively evaluate the role of integrated positron emission tomography computed tomography (PET-CT) in oesophageal carcinoma staging, in predicting prognosis and its influence on surgical management. MATERIALS AND METHODS: Twenty-five consecutive patients with potentially operable, biopsy-proven oesophageal malignancy who undergoing PET-CT from September 2004 to April 2007 were included in this study. Chi-square and Fisher's exact tests were used to compare the accuracy of N staging with PET-CT and CT/endoscopic ultrasound (EUS) using postoperative loco-regional nodal histology as the reference standard. The prognostic value of primary tumour maximum standardized uptake value (SUVmax) was derived using logistic regression. RESULTS: Seventeen men and eight women with a mean age of 62 years were studied. All tumours showed abnormal 2-[(18)F]-fluoro-2-deoxy-d-glucose (FDG) uptake. Fifteen patients underwent surgical resection. There was high concordance between N staging at CT/EUS (14/15) and final histology. PET-CT N staging was discordant with final nodal histology in over half of the patients (8/15). PET-CT detected occult metastases in three patients (12%) that were not identified on CT and new synchronous tumours in two patients (8%). Patient management was altered in 10 patients (40%) as a direct result of PET-CT. No statistically significant association was observed between SUVmax and clinical outcome (p=0.65). CONCLUSION: Integrated PET-CT has a significant incremental value over conventional staging investigations mainly in the detection of distant metastases and synchronous tumours and frequently impacts on patient management.

Production of the refolded oligopeptide-binding protein (OppA) encoded by the citrus pathogen Xanthomonas axonopodis pv. citri

The oligopeptide-binding protein, OppA, binds and ushers oligopeptide substrates to the membrane-associated oligopeptide permease (Opp), a multi-component ABC-type transporter involved in the uptake of oligopeptides expressed by several bacterial species. In the present study, we report the cloning, purification, refolding and conformational analysis of a recombinant OppA protein derived from Xanthomonas axonopodis pv. citri (X. citri), the etiological agent of citrus canker. The oppA gene was expressed in Escherichia coli BL21 (DE3) strain under optimized inducing conditions and the recombinant protein remained largely insoluble. Solubilization was achieved following refolding of the denatured protein. Circular dichroism analysis indicated that the recombinant OppA protein preserved conformational features of orthologs expressed by other bacterial species. The refolded recombinant OppA represents a useful tool for structural and functional analyses of the X. citri protein.

Structural model and ligand interactions of the Xanthomonas axonopodis pv. citri oligopeptide-binding protein

The oligopeptide-binding protein, OppA, ushers oligopeptide substrates to the membrane-associated oligopeptide permease (Opp), a multi-component ABC-type transporter involved in the uptake of oligopeptides by several bacterial species. In the present study, we report a structural model and an oligopeptide docking analysis of the OppA protein expressed by Xanthomonas axonopodis pv. citri (X. citri), the etiological agent of citrus canker. The X. citri OppA structural model showed a conserved three-dimensional structure, irrespective of the low amino acid identities with previously defined structures of Bacillus subtilis and Salmonella typhimurium orthologs. Oligopeptide docking analysis carried out with the proposed model indicated that the X. citri OppA preferentially binds tri- and tetrapeptides. The present study represents the first structural analysis of an OppA ortholog expressed by a phytopathogen and contributes to the understanding of the physiology and nutritional strategies of X. citri.

The use of the Zontik cava filter for temporary implantation to the inferior vena cava.

The authors review the potential for the use of the Zontik retrievable cava filter (CF) for temporary implantation. In the course of their observations, the CF was to be received by 68 patients for the time needed for the treatment of floating thrombi in the inferior vena cava and its tributaries using thrombectomy, thrombolysis or anticoagulants. In 10 patients, the CF was implanted in view of the risk of pulmonary thromboembolism (PTE) during and after obstetric-gynecological and orthopedic operations carried out in the presence of deep venous thrombosis of the lower limbs. After elimination of the risk of PTE the CF was retrieved in 38 (48.7%) patients over the period 2 to 64 days; 4 patients declined filter retrieval; in 3 patients, the procedure ended in failure. In view of the risk of PTE the CF, was left for permanent implantation in 33 patients. Of these, in 8 patients it was left due to embolism to the filter and in 8 patients due to its thrombosis. One patient developed PTE which prompted CF retrieval on the second day following implantation. Thirty patients were examined over the period 12 to 62 months after CF retrieval. No signs of PTF were detected, the inferior vena cava was patent. Based on their own experience the authors investigate the conditions required for temporary implantation of the CF and the indications for its use, factors providing for the minimal risk of the recurrence of venous thrombosis and PTF after filter retrieval, and the possibilities of a broader practical use of the technique. They believe that temporary implantation of the CF is the most prospective trend in endovascular prevention of PTE.