Pumping liquid metal at high temperatures up to 1,673 kelvin.

Heat is fundamental to power generation and many industrial processes, and is most useful at high temperatures because it can be converted more efficiently to other types of energy. However, efficient transportation, storage and conversion of heat at extreme temperatures (more than about 1,300 kelvin) is impractical for many applications. Liquid metals can be very effective media for transferring heat at high temperatures, but liquid-metal pumping has been limited by the corrosion of metal infrastructures. Here we demonstrate a ceramic, mechanical pump that can be used to continuously circulate liquid tin at temperatures of around 1,473-1,673 kelvin. Our approach to liquid-metal pumping is enabled by the use of ceramics for the mechanical and sealing components, but owing to the brittle nature of ceramics their use requires careful engineering. Our set-up enables effective heat transfer using a liquid at previously unattainable temperatures, and could be used for thermal storage and transport, electric power production, and chemical or materials processing.

Role of heterotrophic nitrifiers and aerobic denitrifiers in simultaneous nitrification and denitrification process: a nonconventional nitrogen removal pathway in wastewater treatment.

Bacterial species capable of performing both nitrification and denitrification in a single vessel under similar conditions have gained significance in the wastewater treatment scenario considering their unique character of performing the above reactions under heterotrophic and aerobic conditions respectively. Such a novel strategy often referred to as simultaneous nitrification and denitrification (SND) has a tremendous potential in dealing with various wastewaters having low C : N content, considering that the process needs very little or no external carbon source and oxygen supply thus adding to its cost-effective and environmentally friendly nature. Though like other micro-organisms, heterotrophic nitrifiers and aerobic denitrifiers convert inorganic or organic nitrogen-containing substances into harmless dinitrogen gas in the wastewater, their ecophysiological role in the global nitrogen cycle is still not fully understood. Attempts to highlight the role played by the heterotrophic nitrifiers and aerobic denitrifiers in dealing with nitrogen pollution under various environmental operating conditions will help in developing a mechanistic understanding of the SND process to address the issues faced by the traditional methods of aerobic autotrophic nitrification-anaerobic heterotrophic denitrification.

[Endovascular aneurysm repair (EVAR) : Complication management]. / Endovaskuläre Aneurysmaversorgung (EVAR) : Komplikationsmanagement.

A variety of complications may be experienced during or after endovascular repair (EVAR) of abdominal aortic aneurysms (AAA). Acute procedure-related complications include injury to the access vessels, improper endograft placement, ischaemic and systemic complications as well as the postimplantation syndrome. Femoral pseudoaneurysms, endograft migration, kinking or occlusion, endoleaks and endograft infection are complications that have been observed at follow-up. Meticulous patient selection and preprocedural work-up can reduce the incidence of these complications. The majority of the complications, acute as well those at follow-up, can be dealt with endoluminally. It is of essence, however, that a wide variety of catheters, guidewires, stents, stent-grafts and embolics are readily available in the repertoire of the interventionalist. In a small number of patients with endograft occlusion or infection or with bleeding complications/pseudoaneurysms of the access vessels, open surgical intervention may become necessary. To obtain optimal results, close interdisciplinary co-operation, especially between the interventionist, the vascular surgeon and the anaesthetist is mandatory.

Comparative Evaluation of N-Butyl Cyanoacrylate and Silk Sutures on Healing of Periodontal Flaps: A Clinico Histological Evaluation.

Background The periodontal flap is one of the most frequently employed procedures. Closure of reflected flap is important step in flap surgery. Black silk sutures are most often used material in routine surgical procedures. These suture materials demand more time and effort and expertise from the surgeon. Tissue adhesives have been developed as alternatives to overcome these problems such as cyanoacrylates. Objective The present study is an attempt to compare effectiveness of the black silk suture with cyanoacrylate adhesives in closing reflected periodontal flap. Method Thirty systemically healthy patients who underwent bilateral flap surgery were given 3-0 black silk sutures on one side and N-butyl cyanoacrylate adhesive on the other side to close a surgical incision. All the participants in the study were recalled on the seventh, 21st, 42nd day. Participants were evaluated for healing and plaque accumulation by assessing the gingival index, plaque index, wound healing index. Biopsy specimens were obtained on seventh and 42nd postoperative day. Result The amount of inflammation was less during the first week of healing when cyanoacrylate was compared with silk. However, over a period of 21 days to 42 days, the sites treated with both the materials showed similar healing patterns without any significant difference in the evaluated parameter. Conclusion The result of the study showed that the use of cyanoacrylate for the closure of periodontal flaps results in better initial post-operative healing as compared to closure with silk suture and that this method of closure can be advocated in a routine surgical periodontal practice.

Dictyostelium, a microbial model for brain disease.

BACKGROUND: Most neurodegenerative diseases are associated with mitochondrial dysfunction. In humans, mutations in mitochondrial genes result in a range of phenotypic outcomes which do not correlate well with the underlying genetic cause. Other neurodegenerative diseases are caused by mutations that affect the function and trafficking of lysosomes, endosomes and autophagosomes. Many of the complexities of these human diseases can be avoided by studying them in the simple eukaryotic model Dictyostelium discoideum. SCOPE OF REVIEW: This review describes research using Dictyostelium to study cytopathological pathways underlying a variety of neurodegenerative diseases including mitochondrial, lysosomal and vesicle trafficking disorders. MAJOR CONCLUSIONS: Generalised mitochondrial respiratory deficiencies in Dictyostelium produce a consistent pattern of defective phenotypes that are caused by chronic activation of a cellular energy sensor AMPK (AMP-activated protein kinase) and not ATP deficiency per se. Surprisingly, when individual subunits of Complex I are knocked out, both AMPK-dependent and AMPK-independent, subunit-specific phenotypes are observed. Many nonmitochondrial proteins associated with neurological disorders have homologues in Dictyostelium and are associated with the function and trafficking of lysosomes and endosomes. Conversely, some genes associated with neurodegenerative disorders do not have homologues in Dictyostelium and this provides a unique avenue for studying these mutated proteins in the absence of endogeneous protein. GENERAL SIGNIFICANCE: Using the Dictyostelium model we have gained insights into the sublethal cytopathological pathways whose dysregulation contributes to phenotypic outcomes in neurodegenerative disease. This work is beginning to distinguish correlation, cause and effect in the complex network of cross talk between the various organelles involved. This article is part of a Special Issue entitled Frontiers of Mitochondrial Research.

Risk of cancer incidence before the age of 15 years after exposure to ionising radiation from computed tomography: results from a German cohort study.

The aim of this cohort study was to assess the risk of developing cancer, specifically leukaemia, tumours of the central nervous system and lymphoma, before the age of 15 years in children previously exposed to computed tomography (CT) in Germany. Data for children with at least one CT between 1980 and 2010 were abstracted from 20 hospitals. Cancer cases occurring between 1980 and 2010 were identified by stochastic linkage with the German Childhood Cancer Registry (GCCR). For all cases and a sample of non-cases, radiology reports were reviewed to assess the underlying medical conditions at time of the CT. Cases were only included if diagnosis occurred at least 2 years after the first CT and no signs of cancer were recorded in the radiology reports. Standardised incidence ratios (SIR) using incidence rates from the general population were estimated. The cohort included information on 71,073 CT examinations in 44,584 children contributing 161,407 person-years at risk with 46 cases initially identified through linkage with the GCCR. Seven cases had to be excluded due to signs possibly suggestive of cancer at the time of first CT. Overall, more cancer cases were observed (O) than expected (E), but this was mainly driven by unexpected and possibly biased results for lymphomas. For leukaemia, the SIR (SIR = O/E) was 1.72 (95 % CI 0.89-3.01, O = 12), and for CNS tumours, the SIR was 1.35 (95 % CI 0.54-2.78, O = 7). Despite careful examination of the medical information, confounding by indication or reverse causation cannot be ruled out completely and may explain parts of the excess. Furthermore, the CT exposure may have been underestimated as only data from the participating clinics were available. This should be taken into account when interpreting risk estimates.

[The simultaneous appearance of three uncommon tumours]. / Synchrones Auftreten dreier seltener Tumoren.

A 70-year-old woman presented with nasal obstruction and pain projecting onto the left cheek. The face seemed asymmetric including exophthalmus on the right side. Nasal endoscopic inspection revealed a sarcomatous tumor located on the middle turbinate. The CT showed that the tumor filled the left maxillary sinus completely and had eroded the maxillary bone. In addition, a round, sharply defined intraorbital neoplasm on the right side was identified in the contrast-enhanced MRI. Histological examination of the extirpated intraorbital tumour showed a neurilemmoma. A tissue biopsy of the intranasal tumour falsely suggested an intestinal adenocarcinoma. Multiple neoplasms suspicious of disseminated lung metastases were detected in the CT of the thorax. One round lesion removed by thoracoscopy revealed a carcinoid. The intranasal tumour was excised completely and the histology proved beyond doubt an inverted papilloma.

Modification of physicochemical properties of chitosan to improve its pharmaceutical and agrochemical potential applications.

Chitosan has received much more attention as a functional biopolymer with applications in pharmaceuticals, agricultural, drug delivery systems and cosmetics. The objectives of present investigation were to carry out modification of chitosan for enhancement of aqueous solubility, which will impart increased solubility and dissolution rate of poorly soluble drug itraconazole (ITZ) and also evaluate the modified chitosan for soyabean seed germination studies. The modification of chitosan was accomplished through the antisolvent precipitation method; employing five carboxylic acids. The resulting products were assessed for changes in molecular weight, degree of deacetylation, solubility and solid state characterization. Subsequently, the modified chitosan was complexed with itraconazole using the co-grinding technique. The prepared formulations were evaluated for solubility, FTIR (Fourier-transform infrared spectroscopy), PXRD (Powder X-ray diffraction), in-vitro dissolution studies. Furthermore the effect of modified chitosan has been evaluated on soybean seed germination. Results demonstrated that, modified chitosan improves self and solubility of itraconazole by six folds. As there was increased degree of deacetylation of chitosan leads to improvement in solubility. The results of FTIR showed the slight shifting of peaks in co-grind formulations of itraconazole. Formulations showed reduction in crystallinity of drug which leads to enhancement in dissolution rate as compared to pure itraconazole. Retention of property of seed germination was observed with modified chitosan at optimum concentration of 3 % w/v, with benefit of enhanced aqueous solubility of chitosan. This positive result paves the way for the advancement of pharmaceutical and agrochemical products employing derivatives of chitosan.

[Diagnosis of and therapy for hepatocellular carcinoma]. / Diagnostik und Therapie des hepatozellulären Karzinoms.

The interdisciplinary guidelines at the S3 level on the diagnosis of and therapy for hepatocellular carcinoma (HCC) constitute an evidence- and consensus-based instrument that is aimed at improving the diagnosis of and therapy for HCC since these are very challenging tasks. The purpose of the guidelines is to offer the patient (with suspected or confirmed HCC) adequate, scientifically based and up-to-date procedures in diagnosis, therapy and rehabilitation. This holds not only for locally limited or focally advanced disease but also for the existence of recurrences or distant metastases. Besides making a contribution to an appropriate health-care service, the guidelines should also provide the foundation for an individually adapted, high-quality therapy. The explanatory background texts should also enable non-specialist but responsible colleagues to give sound advice to their patients concerning specialist procedures, side effects and results. In the medium and long-term this should reduce the morbidity and mortality of patients with HCC and improve their quality of life.

Concomitant pulmonary disease is common among patients with extrapulmonary TB.

BACKGROUND: Microbiologic screening of extrapulmonary TB (EPTB) patients could inform recommendations for aerosol precautions and close contact prophylaxis. However, this is currently not routinely recommended in India. Therefore, we estimated the proportion of Indian patients with EPTB with microbiologic evidence of pulmonary TB (PTB).METHODS: We characterized baseline clinical, radiological and sputum microbiologic data of 885 adult and pediatric TB patients in Chennai and Pune, India, between March 2014 and November 2018.RESULTS: Of 277 patients with EPTB, enhanced screening led to the identification of 124 (45%) with concomitant PTB, including 53 (19%) who reported a cough >2 weeks; 158 (63%) had an abnormal CXR and 51 (19%) had a positive sputum for TB. Of 70 participants with a normal CXR and without any cough, 14 (20%) had a positive sputum for TB. Overall, the incremental yield of enhanced screening of patients with EPTB to identify concomitant PTB disease was 14% (95% CI 12-16).CONCLUSIONS: A high proportion of patients classified as EPTB in India have concomitant PTB. Our results support the need for improved symptom and CXR screening, and recommends routine sputum TB microbiology screening of all Indian patients with EPTB.

Measuring TB drug levels in the hair in adults and children to monitor drug exposure and outcomes.

INTRODUCTION: Testing for anti-TB drugs in small hair samples may serve as a non-invasive tool to measure cumulative drug exposure and/or adherence, as these determine treatment success. We aimed to assess how well hair assays of TB drugs predict TB treatment outcomes.METHODS: A small thatch of hair, ~30 strands, was cut from the occipital region in adults and children from a prospective TB cohort in India. Isoniazid (INH), acetyl-INH and pyrazinamide (PZA) were extracted from the hair samples and quantified using liquid-chromatography-tandem mass spectrometry. The relationship between drug concentrations in hair and time to unfavourable outcomes was assessed using Cox-proportional hazards regression models.RESULTS: A two-fold increase in hair acetyl-INH concentrations in the 264 participants in our cohort with hair assays for TB drugs indicated a lower hazard of unfavourable TB treatment outcomes (aHR 0.67, 95%CI 0.44-1.02) and TB treatment failure (aHR 0.65, 95%CI 0.42-1.01). Higher summed concentrations (a summed measure of INH and acetyl-INH) indicated a lower hazard of treatment failure (aHR 0.69, 95%CI 0.45-1.05)CONCLUSION: Hair levels of INH and its metabolite may predict TB treatment outcomes, indicating the potential utility of this measure to assess and optimise TB treatment outcomes.

[Peripheral vascular disease of iliac and femoro-popliteal arteries: state-of-the-art endoluminal revascularization]. / Arterielle Verschlusskrankheit der Becken- und Oberschenkelarterien: State-of-the-art-Rekanalisation.

Endoluminal therapy is indicated in lower extremity ischaemia with Fontaine grades IIb, III and IV. In the presence of significant limitations, interventions are carried out even in grade IIa claudicants. In addition to the TASC A and B lesions, TASC C and D lesions are increasingly being treated endoluminally as well. Presently, technical success rates of revascularization procedures are above 90% in the iliac vessels and between 79% and 95% in the femoro-popliteal segments. Concentric, non-calcified iliac stenoses are primarily treated with balloon angioplasty (PTA) followed by optional stenting when necessary. For occlusions and heavily calcified lesions, primary stenting is recommended. Primary PTA is the mainstay of treatment in femoro-popliteal vessels with stents being used as a "bail-out" option in case of suboptimal PTA. However, initial reports proving the superiority of primary stenting over PTA with optional stenting have already appeared. Results of PTA with drug-coated balloons for prevention of early restenosis are promising. In the near future, primary PTA with optional stenting in the femoro-popliteal segments may give way to drug-coated balloon angioplasty or primary stenting.

Assessment of the Xpert assay among adult pulmonary tuberculosis suspects with and without diabetes mellitus.

SETTING: Pune and Pimpri-Chinchwad Municipal Corporation area, Maharashtra State, India.OBJECTIVE: To assess the sensitivity and specificity of the Xpert® MTB/RIF assay among adults with suspected pulmonary tuberculosis (PTB) and with or without diabetes (DM).DESIGN: As part of a prospective cohort study, we screened 2359 adults presumed to have PTB with no history of TB. All individuals underwent testing for two sputum smears, culture, Xpert, glycated haemoglobin and fasting blood sugar. We calculated sensitivity and specificity of Xpert by comparing it with TB sputum culture result as a gold standard.RESULTS: Among screened individuals, 483 (20%) were diagnosed with DM and 1153 (49%) with pre-DM; 723 (31%) had no DM. Overall sensitivity of Xpert was 96% (95%CI 95-97) and specificity was 91% (95%CI 89-93). Xpert sensitivity was significantly higher among DM group (98%) than in the 'No DM' (95%; P < 0.01) and pre-DM (96%; P < 0.05) groups. Among sputum smear-negative individuals, Xpert sensitivity was higher in the DM group than in the No DM (92% vs. 82%; P = 0.054) and pre-DM group (92% vs. 82%; P = 0.037).CONCLUSION: High sensitivity and specificity of Xpert underscores the need for its rapid scale up for the early detection of TB in settings with a high dual burden of TB and DM.

Chemoocclusion vs chemoperfusion for treatment of advanced hepatocellular carcinoma: a randomised trial.

AIMS: Transarterial chemoembolization (TACE) can be associated with considerable toxicity and treatment-associated mortality. Transient transarterial chemoocclusion (TACO) using degradable starch microspheres (DSM) has been proposed as a potentially safer alternative while maintaining anti-tumour efficiency. In a randomised phase II trial TACO was compared to transarterial chemoperfusion without DSM (TACP). METHODS: Seventy-four patients with advanced HCC were randomised to two treatment arms: (i) TACO (600-1200 mg DSM) and (ii) TACP. In both arms regional chemotherapy consisted of cisplatin (100 mg/m2) and doxorubicin (60 mg/m2). Both arms were corresponding in terms of age, gender, liver performance state, and tumour-stage. A maximum of six treatment cycles was applied in monthly intervals. Follow-up was performed in terms of tumour response, time to progression, survival and quality of life. RESULTS: Tumour response rates did not differ significantly between the two treatment arms, however, there was a tendency towards higher response rates in the TACO arm (TACO vs TACP): partial response: 26 vs 9%, stable disease: 41 vs 55%, progressive disease: 33 vs 36%. Time to tumour progression (32 vs 27 weeks), and overall survival (60 vs 69 weeks) were not significantly different. Grade 4 adverse events were rare in both arms and treatment-associated mortality was not observed. In addition, there was no significant difference in terms of quality of life under therapy (EORTC). CONCLUSION: TACO with DSM did not improve response or survival significantly compared to TACP in advanced non-resectable HCC.

Inhibition of granulocyte-macrophage colony-stimulating factor (GM-CSF) activity by suramin and suramin analogues is correlated to interaction with the GM-CSF nucleotide-binding site.

Suramin and suramin analogues strongly inhibit both nucleotide interaction with the nucleotide-binding site of granulocyte-macrophage colony-stimulating factor (GM-CSF) and bioactivity of the molecule as assessed by competition photoaffinity labeling and cell proliferation assay, respectively. The half-maximal inhibition of cell proliferation by suramin occurs at 68 +/- 2.5 microM; three suramin analogues achieved comparable activity. The degree of competitive inhibition of nucleotide-binding by these compounds and the inhibition of GM-CSF bioactivity are correlated such that the compounds show similar rank-order by both of these methods. The strong interaction of suramin and related compounds with the nucleotide-binding site may mimic nucleotide-mediated inhibition of GM-CSF bioactivity and may be an important mechanism by which suramin acts as a pharmacological anti-growth factor agent.

Site-specific photobiotinylation of immunoglobulins, fragments and light chain dimers.

Herein we report a new method to rapidly photoinsert biotin into a specific and highly conserved site on the Ig structure using a mild photochemical activation step. This site resides in the Fv fragment and involves invariant residues which provide base stacking interactions to the purine ring of ATP (Rajagopalan et al. (1996) Proc. Natl. Acad. Sci. USA 93, 6019-6024). Biotin was coupled to either the phosphate or the ribose of the 8-azidopurine nucleotide or nucleoside photoaffinity probe and shown to insert into the affinity site efficiently. Several monoclonal and polyclonal antibodies, as well as enzymatic and recombinant antibody fragments and light chain dimers were photoaffinity biotinylated and used in ELISA, FACS and Western blots. The selectivity of this site-specific biotinylation method also allows for biotinylation of antibodies in culture supernatants and immune sera without prior purification. Because the biotinylation takes place under physiological conditions and within a short time period, photobiotinylation would be the preferred method for antibodies which are easily damaged by classical non-site specific random biotinylation chemistry.

The novel silatecan 7-tert-butyldimethylsilyl-10-hydroxycamptothecin displays high lipophilicity, improved human blood stability, and potent anticancer activity.

We describe the rational design and synthesis of B- and A, B-ring-modified camptothecins. The key alpha-hydroxy-delta-lactone pharmacophore in 7-tert-butyldimethylsilyl-10-hydroxycamptothecin (DB-67, 14) displays superior stability in human blood when compared with clinically relevant camptothecin analogues. In human blood 14 displayed a t(1/2) of 130 min and a percent lactone at equilibrium value of 30%. The tert-butyldimethylsilyl group renders the new agent 25-times more lipophilic than camptothecin, and 14 is readily incorporated, as its active lactone form, into cellular and liposomal bilayers. In addition, the dual 7-alkylsilyl and 10-hydroxy substitution in 14 enhances drug stability in the presence of human serum albumin. Thus, the net lipophilicity and the altered human serum albumin interactions together function to promote the enhanced blood stability. In vitro cytotoxicity assays using multiple different cell lines derived from eight distinct tumor types indicate that 14 is of comparable potency to camptothecin and 10-hydroxycamptothecin, as well as the FDA-approved camptothecin analogues topotecan and CPT-11. In addition, cell-free cleavage assays reveal that 14 is highly active and forms more stable top1 cleavage complexes than camptothecin or SN-38. The impressive blood stability and cytotoxicity profiles for 14 strongly suggest that it is an excellent candidate for additional in vivo pharmacological and efficacy studies.

First experience and technical aspects of isolated liver perfusion for extensive liver metastasis.

BACKGROUND: New drugs and modalities for locoregional tumor treatment in recent years may offer new potential for isolated liver perfusion in patients with nonresectable liver tumors. The purpose of this study was to prove the feasibility of arterial isolated liver perfusion and to assess the tolerance of perfusion with high-dose tumor necrosis factor (TNF). METHODS: Twelve patients with extensive liver metastases previously treated unsuccessfully with systemic chemotherapy underwent isolated hyperthermic liver perfusion using a heart-lung machine. High doses of mitomycin were administered in the first six and a combination of TNF and melphalan in the last six patients. RESULTS: No operative death occurred and no direct postoperative liver failure was observed in any patient. In cases of variations of the arterial hepatic blood supply, the perfusion was done through the splenic artery or an angiography catheter. Histologic analysis of tumor biopsy specimens obtained on the first postoperative day revealed major tumor necrosis in 8 of 12 patients. CONCLUSIONS: Isolated arterial perfusion of the liver is a complex surgical procedure that is feasible in patients with anatomic variations of the hepatic artery. The remarkable histologic response to perfusion in several pretreated patients, especially after application of high-dose TNF and melphalan, suggests that this modality is very effective in tumor killing.

Photoaffinity labeling of rat liver microsomal steroid 5 alpha-reductase by 2-azido-NADP+.

Preincubation of female rat liver microsomal preparations with [2'-32P]2N3-NADP+ followed by photolysis with UV light (254 nm) and analysis by SDS-PAGE/autoradiography showed incorporation of 32P into at least 3 major protein bands in the molecular weight range of 14-97 Kd. Labeling of a 26 kD band, the apparent molecular weight of 5 alpha-reductase in liver microsomes, was accompanied by a loss of enzyme activity, consistent with its covalent modification. The inclusion of 20-fold excess NADP+ (100 microM) completely inhibited the incorporation of [2'-32P]2N3-NADP+ and preserved the enzyme activity, whereas excess NAD+ (100 microM) failed to protect 5 alpha-reductase (5 alpha R) activity. Similar results were obtained with the detergent-solubilized form of 5 alpha R. Polyethylene glycol (PEG) fractionation of detergent-solubilized preparations of 5 alpha R showed that all the 5 alpha R activity could be recovered in the 6.5% pellet with a 3-4-fold increase in the specific activity. photolysis of this fraction with [2'-32P]2N3-NADP+ resulted in approximately 2-fold increase in 32P labeling of the 5 alpha R band. Increasing photolysis time and concentration of the [2'-32P]2N3-NADP+ indicated that the half-life for photoincorporation and the apparent Kd were 1.0 min and 2 microM, respectively. These results suggest that 2N3-NADP+ is an effective probe of the NADP(H) binding site of 5 alpha R, and is a useful marker during purification of the enzyme.