Activity of oxantel pamoate monotherapy and combination chemotherapy against Trichuris muris and hookworms : revival of an old drug

BACKGROUND: It is widely recognized that only a handful of drugs are available against soil-transmitted helminthiasis, all of which are characterized by a low efficacy against Trichuris trichiura, when administered as single doses. The re-evaluation of old, forgotten drugs is a promising strategy to identify alternative anthelminthic drug candidates or drug combinations. METHODOLOGY: We studied the activity of the veterinary drug oxantel pamoate against Trichuris muris, Ancylostoma ceylanicum and Necator americanus in vitro and in vivo. In addition, the dose-effect of oxantel pamoate combined with albendazole, mebendazole, levamisole, pyrantel pamoate and ivermectin was studied against T. muris in vitro and additive or synergistic combinations were followed up in vivo. PRINCIPAL FINDINGS: We calculated an ED50 of 4.7 mg/kg for oxantel pamoate against T. muris in mice. Combinations of oxantel pamoate with pyrantel pamoate behaved antagonistically in vitro (combination index (CI) = 2.53). Oxantel pamoate combined with levamisole, albendazole or ivermectin using ratios based on their ED50s revealed antagonistic effects in vivo (CI = 1.27, 1.90 and 1.27, respectively). A highly synergistic effect (CI = 0.15) was observed when oxantel pamoate-mebendazole was administered to T. muris-infected mice. Oxantel pamoate (10 mg/kg) lacked activity against Ancylostoma ceylanicum and Necator americanus in vivo. CONCLUSIONSIGNIFICANCE: Our study confirms the excellent trichuricidal properties of oxantel pamoate. Since the drug lacks activity against hookworms it is necessary to combine oxantel pamoate with a partner drug with anti-hookworm properties. Synergistic effects were observed for oxantel pamoate-mebendazole, hence this combination should be studied in more detail. Since, of the standard drugs, albendazole has the highest efficacy against hookworms, additional investigations on the combination effect of oxantel pamoate-albendazole should be launche

Activity of tribendimidine and praziquantel combination therapy against the liver fluke Opisthorchis viverrini in vitro and in vivo

Opisthorchiasis, caused by the liver fluke Opisthorchis viverrini, a food-borne trematode, is an important public health problem; however, only a single drug, praziquantel is available. We investigated tribendimidine-praziquantel combinations against O. viverrini in vitro and in vivo. The IC50 values of 0.16μg/ml and 0.05μg/ml were determined for praziquantel and tribendimidine, respectively, against adult O. viverrini in vitro. When O. viverrini was exposed to both drugs simultaneously (using a drug ratio based on the IC50 (1:3.2)) a synergistic effect was calculated (combination index (CI) at the IC50=0.7). A similar result was observed when drug addition in vitro was spaced by the respective half-lives of the drugs (a CI of 0.78 at the IC50 for tribendimidine followed by praziquantel and a CI of 0.47 at the IC50 for praziquantel followed by tribendimidine). In vivo median-effect dose (ED50) values of 191mg/kg and 147mg/kg were calculated for praziquantel and tribendimidine, respectively. Low to moderate worm burden reductions (38-62%) were observed in O. viverrini infected hamsters when both drugs were administered simultaneously or on subsequent days, pointing to antagonistic effects in vivo. Further studies are necessary to understand the striking differences between the in vitro and in vivo observations using combinations of praziquantel and tribendimidine on O. viverrin

Economic and Environmental Assessment of Biomass Power Plants in Southern Italy

In 2019, Europe adopted the New Green Deal as a strategic plan to become a competitive, resource-efficient, and driven economy by reducing its gas emissions and carbon footprint. Due the COVID-19 pandemic, this strategic plan was recently updated to expedite the green transition of European industries. Therefore, the present paper deals with the problem of deciding an appropriate size for a biomass plant that directly produces electric energy by means of two different conversion processes: combustion and gasification. After an initial estimation of the energy potential in western Sicily, GIS data of biomass growth were used to identify the appropriate size for the power plants under investigation. The economic feasibility of biomass utilization was evaluated over a capacity range of 10 to 30 MW, considering total capital investments, revenues from energy sales, and total operating costs. Moreover, the effect of variations on incentive prices was analyzed by means of a sensitivity analysis. Comparing the different plant solutions considered, the environmental sustainability was also analyzed using the life cycle assessment (LCA) approach. The results showed that the combustion solution had a higher profitability and a lower environmental impact for each plant size. The obtained results also demonstrated that providing power from residual biomass in small agricultural communities would significantly reduce their environmental impacts while improving the economic feasibility of their waste management practices

Data Integration for Open Data on the Web

In this lecture we will discuss and introduce challenges of integrating openly available Web data and how to solve them. Firstly, while we will address this topic from the viewpoint of Semantic Web research, not all data is readily available as RDF or Linked Data, so we will give an introduction to different data formats prevalent on the Web, namely, standard formats for publishing and exchanging tabular, tree-shaped, and graph data. Secondly, not all Open Data is really completely open, so we will discuss and address issues around licences, terms of usage associated with Open Data, as well as documentation of data provenance. Thirdly, we will discuss issues connected with (meta-)data quality issues associated with Open Data on the Web and how Semantic Web techniques and vocabularies can be used to describe and remedy them. Fourth, we will address issues about searchability and integration of Open Data and discuss in how far semantic search can help to overcome these. We close with briefly summarizing further issues not covered explicitly herein, such as multi-linguality, temporal aspects (archiving, evolution, temporal querying), as well as how/whether OWL and RDFS reasoning on top of integrated open data could be help

Secretory breast carcinoma with metastatic sentinel lymph node

BACKGROUND: Secretory mammary carcinoma is a rare breast neoplasia originally described in children but sometimes also found in adults. It presents a more favourable outcome than more common histological types of breast carcinoma; published literature in fact reports only a few cases with axillary lymph node metastases and only four cases with distant metastases. CLINICAL PRESENTATION: In this paper we report a rare case of secretory breast carcinoma with axillary lymph node metastases in a 33-year-old woman. To our knowledge, this is the first case of secretory carcinoma involving biopsy of the sentinel lymph node and investigation of the e-cadherin expression. We found positivity for e-cadherin, which would support the hypothesis that this type of tumour is a variant of the infiltrating ductal carcinoma. CONCLUSION: After a careful analysis of reported data, we have come to the conclusion that the treatment of choice for patients with secretory breast carcinoma should be conservative surgery with sentinel lymph node biopsy, followed by accurate follow-up. We are of the opinion that while post-operative radiotherapy is indicated in adult patients who have undergone quadrantectomy, it should not be used in children. Although several cases of secretory carcinoma have been treated with adjuvant chemotherapy, there are still no reliable data regarding the real value of such a choice

Two cases of monomicrobial intraabdominal abscesses due to KPC - 3 Klebsiella pneumoniae ST258 clone

<p>Abstract</p> <p>Background</p> <p>Knowledge of the etiology of pyogenic liver and pancreatic abscesses is an important factor in determining the success of combined surgical and antibiotic treatment. Literature shows geographical variations in the prevalence and distribution of causative organisms, and the spread of <it>Klebsiella pneumoniae </it>carbapenemase-producing bacteria is an emerging cause of abdominal infections.</p> <p>Case presentation</p> <p>We herein describe two cases of intra-abdominal abscesses due to monomicrobial infection by <it>Klebsiella pneumoniae </it>Sequence Type 258 producing <it>K. pneumoniae </it>carbapenemase 3 (KPC-Kp). In case 1, a 50-year-old HIV-negative Italian woman with chronic pancreatitis showed infection of a pancreatic pseudocystic lesion caused by KPC-Kp. In case 2, a 64-year-old HIV- negative Italian woman with pancreatic neoplasm and liver metastases developed a liver abscess due to KPC after surgery. Both women were admitted to our hospital but to different surgical units. The clonal relationship between the two isolates was investigated by pulsed-field gel electrophoresis (PFGE). In case 2, the patient was already colonized at admission and inter-hospital transmission of the pathogen was presumed. A long-term combination regimen of colistin with tigecycline and percutaneous drainage resulted in full recovery and clearance of the multidrug-resistant (MDR) pathogen.</p> <p>Conclusions</p> <p>Timely microbiological diagnosis, the combined use of new and old antibiotics and radiological intervention appeared to be valuable in managing these serious conditions. The emergence and dissemination of MDR organisms is posing an increasing challenge for physicians to develop new therapeutic strategies and control and prevention frameworks.</p

An Algorithm for Earthquakes Clustering based on Maximum Likelihood

In this paper we propose a clustering technique set up to separate and find out the two main components of seismicity: the background seismicity and the triggered one. We suppose that a seismic catalogue is the realization of a non homogeneous space-time Poisson clustered process, with a different parametrization for the intensity function of the Poisson-type component and of the clustered (triggered) component. The method here proposed assigns each earthquake to the cluster of earthquakes, or to the set of independent events, according to the increment to the likelihood function, computed using the conditional intensity function estimated by maximum likelihood methods and iteratively changing the assignment of the events; after a change of partition, MLE of parameters are estimated again and the process is iterated until there is no more improvement in the likelihood

From lab to industry: Scaling up green geopolymeric mortars manufacturing towards circular economy

Construction is nowadays considered an extremely energy intensive industry and one of the main sources of environmental pollution in the world. Therefore, the research and the development of novel energy-saving manufacturing processes and sustainable construction materials is more than ever urgent and challenging. This paper aims at identifying the industrial process for the production of novel geopolymers to be used as a greener substitute for cement, especially the Portland one, widely used for structural applications to significantly reduce the environmental impact of the construction industry. Here, the materials sustainability and the manufacturing process are improved by valorising and reusing wastes, deriving from the pulp-paper industry, as raw materials. This industry generates a great quantity of wastes that represent a real concern both for their environmental impact and cost of disposal. The new industrial process was evaluated after scaling up the laboratory procedure to an industrial dimension. Consequently, each small-scale process was deeply analysed (raw materials involved and processes) and transposed into a massive-production. The most relevant processes that show an elevated environmental impact were identified and the energy consumption of the whole process has been assessed resulting, for the analysed geopolymeric product, an embodied energy of 645 MJ/ton, being about one sixth of the OPC. Moreover, a preliminary economic analysis has been conducted in terms of raw materials involved in the proposed industrial process revealing a decreasing cost per ton increasing the waste recycling. All considered, the main conclusions are that the industrial scale up of the proposed geopolymeric product, assessed for the first time in literature along with the related proposed considerations, could be highly competitive to the Portland production involving greener processes with a much lower energy consumption and a greater financial saving by improving the wastes quantity