Unexpected Variation of the Codeine/Morphine Ratio Following Fatal Heroin Overdose

Postmortem samples from 14 cases of suspected heroin overdose were subjected to a preliminary systematic toxicological analysis in order to highlight the presence of unknown exogenous compounds (e.g., drugs of abuse, alcohol) that may have played a role in the mechanism of death. This analysis unveiled histories of poly-drug use in seven of the cases under investigation. Moreover, the concentrations of morphine and codeine in the brain were also investigated, and the results were compared with the data obtained from the blood specimens. The concentration of morphine in blood ranged from 33 to 688 ng/mL, while the concentration of codeine ranged from 0 to 193 ng/mL. However, in the brain, the concentration of morphine was found to be between 85 and 396 ng/g, while the levels of codeine ranged from 11 to 160 ng/g. The codeine/morphine ratio in the blood ranged from 0.043 to 0.619; however, in the brain, the same ratio was found to be between 0.129 and 0.552. In most cases, a significantly higher codeine/morphine ratio was found in the brain, suggesting the accumulation of codeine in brain tissue due its high lipophilicity as compared with morphine

Metagenomic analysis through the extended Burrows-Wheeler transform

Background: The development of Next Generation Sequencing (NGS) has had a major impact on the study of genetic sequences. Among problems that researchers in the field have to face, one of the most challenging is the taxonomic classification of metagenomic reads, i.e., identifying the microorganisms that are present in a sample collected directly from the environment. The analysis of environmental samples (metagenomes) are particularly important to figure out the microbial composition of different ecosystems and it is used in a wide variety of fields: for instance, metagenomic studies in agriculture can help understanding the interactions between plants and microbes, or in ecology, they can provide valuable insights into the functions of environmental communities. Results: In this paper, we describe a new lightweight alignment-free and assembly-free framework for metagenomic classification that compares each unknown sequence in the sample to a collection of known genomes. We take advantage of the combinatorial properties of an extension of the Burrows-Wheeler transform, and we sequentially scan the required data structures, so that we can analyze unknown sequences of large collections using little internal memory. The tool LiME (Lightweight Metagenomics via eBWT) is available at https://github.com/veronicaguerrini/LiME. Conclusions: In order to assess the reliability of our approach, we run several experiments on NGS data from two simulated metagenomes among those provided in benchmarking analysis and on a real metagenome from the Human Microbiome Project. The experiment results on the simulated data show that LiME is competitive with the widely used taxonomic classifiers. It achieves high levels of precision and specificity - e.g. 99.9% of the positive control reads are correctly assigned and the percentage of classified reads of the negative control is less than 0.01% - while keeping a high sensitivity. On the real metagenome, we show that LiME is able to deliver classification results comparable to that of MagicBlast. Overall, the experiments confirm the effectiveness of our method and its high accuracy even in negative control samples

Slicings of parallelogram polyominoes: Catalan, schröder, baxter, and other sequences

We provide a new succession rule (i.e. generating tree) associated with Schröder numbers, that interpolates between the known succession rules for Catalan and Baxter numbers. We define Schröder and Baxter generalizations of parallelogram polyominoes, called slicings, which grow according to these succession rules. In passing, we also exhibit Schröder subclasses of Baxter classes, namely a Schröder subset of triples of non-intersecting lattice paths, a new Schröder subset of Baxter permutations, and a new Schröder subset of mosaic floorplans. Finally, we define two families of subclasses of Baxter slicings: the m-skinny slicings and the m-rowrestricted slicings, for m ∈ N. Using functional equations and the kernel method, their generating functions are computed in some special cases, and we conjecture that they are algebraic for any m

Comparison between Eight-Axis Articulated Robot and Five-Axis CNC Gantry Laser Metal Deposition Machines for Fabricating Large Components

Featured Application: Laser metal deposition of large axisymmetric components. Laser metal deposition (LMD) is an additive manufacturing (AM) process capable of producing large components for the aerospace and oil and gas industries. This is achieved by mounting the deposition head on a motion system, such as an articulated robot or a gantry computer numerical control (CNC) machine, which can scan large volumes. Articulated robots are more flexible and less expensive than CNC machines, which on the other hand, are more accurate. This study compares two LMD systems with different motion architectures (i.e., an eight-axis articulated robot and a five-axis CNC gantry machine) in producing a large gas turbine axisymmetric component. The same process parameters were applied to both machines. The deposited components show no significant differences in geometry, indicating that the different performances in terms of accuracy of the two machines do not influence the outcome. The findings indicate that LMD can consistently produce large-scale axisymmetric metal components with both types of equipment. For such an application, the user has the option of using an articulated robot when flexibility and cost are essential, such as in a research context, or a CNC machine where ease of programming and process standardization are important elements, such as in an industrial environment

Enhancing productivity and efficiency in conventional laser metal deposition process for Inconel 718 - part I: the effects of the process parameters

The sustainable energy transition has spurred the development of technologies that minimize material and energy waste, such as additive manufacturing (AM). Laser metal deposition (LMD) is a promising AM technique, but its complexity and limited automation hinder its implementation in production chains. To enhance productivity, the high deposition rate LMD (HDR-LMD) technology has been developed, requiring advanced equipment and powerful laser sources. In contrast, the conventional LMD (C-LMD) process is simpler and less expensive to implement. This study aims to optimize the productivity and efficiency of C-LMD by adjusting laser power, scan speed, powder feed rate, and standoff distance on Inconel 718 single tracks. An innovative approach eliminates the need for cutting specimens to evaluate single tracks, allowing comprehensive geometric and performance characterization with limited operator involvement, making the analysis quicker and more robust. An extensive experimental campaign was conducted to examine the influence of process parameters on track geometry, productivity, and efficiency. A multi-objective optimization procedure identified parameter combinations maximizing productivity while maintaining high efficiency and desirable clad shape. The study attained deposition rates ranging from 700 to 800 g/h, with powder catchment efficiency ranging between 75 and 90%. These results were achieved using parameters including 1775 W of laser power, scan speeds ranging from 960 to 1140 mm/min, powder feed rates between 810 and 1080 g/h, and standoff distance of 9 mm. The study also clearly indicated that further potential for improving C-LMD process performance may be possible. The findings gathered in this paper are the base for the further optimization presented in the second part of the work, which is focused on multi-pass multi-layer and reaches deposition rates of 1500 g/h, promoting the implementation of C-LMD process at industrial level

Enhancing productivity and efficiency in conventional laser metal deposition process for Inconel 718 – Part II: advancing the process performance

This paper is the second part of a work focused on optimizing the performance of conventional Laser Metal Deposition (C-LMD) process for Inconel 718 (IN718). In Part I, through an extensive experimental campaign on single tracks, the interplay between process parameters and their impact on the deposition rate, powder catchment efficiency, and clad geometry is examined. The parameters investigated include laser power, scan speed, powder feed rate, and standoff distance. By systematically adjusting these parameters, the aim is to identify optimal conditions that maximize productivity while maintaining a favorable clad shape for multi-pass multi-layer depositions. Part II starts from the findings and results of Part I by continuing the optimization on thick wall structures. These are utilized to assess the effect of 3D geometrical process parameters, specifically hatch spacing and Z-step, on process performance and stability. Based on the findings, further optimization procedure is presented, pushing the boundaries of the C-LMD process for IN718. By fine-tuning the process parameters, the capability of the C-LMD process to deposit fully dense IN718 with a productivity of 1500 g/h and a powder catchment efficiency of 70% is demonstrated. These results highlight the potential of C-LMD as a viable manufacturing technique for efficiently fabricating large components. Overall, this study contributes to a deeper understanding of the relationship between process parameters and performance in C-LMD for IN718. The insights gained from this research can guide the development of efficient and cost-effective LMD strategies, facilitating the practical implementation of this process in various industries

Tonic-clonic seizures as a possible complication for cerebrospinal fluid leakage after intradural spinal surgery, a case report

Abstract Background Cerebrospinal fluid leakage is a well-known spinal surgery complication, especially in adults population. Pseudomeningocele is its most common manifestation and it can bring to some conditions, such as intracranial hypotension, infections and wound healing complication. Epilepsy is not classically associated to CSF leakage. We described a case of a female patient who developed tonic-clonic seizures associated with a pseudomeningocele after a detethering surgery. Case description A 16 year old female was admitted to our department for surgical treatment of a tethered cord for a sacral lipoma. Her medical history was remarkable mental retardation with psychiatric disturbs and hypothyroidism. She underwent a surgical intervention for the detethering of conus and dura was closed by a suture and fibrin glue. During third postoperative day she started to suffer a severe occipital headache, followed by tonic-clonic seizures. During suture removal, a collection suspected for a pseudomeningocele was found and chemical and radiological exams confirmed the dubious. Despite a continuous bed rest, collection continued to form. So, we decided to perform a surgical revision and to close dural defect. After intervention, patient did not suffer postural headache anymore and after 3 and 6 months she was found in good health. Conclusion We described the importance of significant morbidity, i.e. that of tonic clonic seizures as a sign of an occult CSF leakage after spinal surgery. Here, hydrocephalus as a condition was present, the change in pressure of CSF can determine seizures as well as promote this complication. A pseudomeningocele is not a trivial complication

Molecular characterization of the meq gene of Marek\u2019s disease viruses detected in unvaccinated backyard chickens reveals the circulation of low- and high-virulence strains

Marek's disease (MD) is an important lymphoproliferative disease of chickens, caused by Gal lid alphaherpesvirus 2 (GaHV-2). Outbreaks are commonly reported in commercial flocks, but also in backyard chickens. Whereas the molecular characteristics of GaHV-2 strains from the commercial poultry sector have been reported, no recent data are available for the rural sector. To fill this gap, 19 GaHV-2 strains detected in 19 Italian backyard chicken flocks during suspected MD outbreaks were molecularly characterized through an analysis of the meq gene, the major GaHV-2 oncogene. The number of four consecutive prolines (PPPP) within the proline-rich repeats of the Meq transactivation domain, the proline content, and the presence of amino acid (aa) substitutions were determined. Phylogenetic analysis was performed using the Maximum Likelihood method. Sequence analysis revealed a heterogeneous population of GaHV-2 strains circulating in Italian backyard flocks. Seven strains, detected from birds affected by classical MD, showed a unique meq isoform of 418 aa with a very high number of PPPP motifs. Molecular and clinical features are suggestive of a low oncogenic potential of these strains. The remaining 12 strains, detected from flocks experiencing acute MD, transient paralysis, or sudden death, had shorter Meq protein isoforms (298 or 339 aa) with a lower number of PPPP motifs and point mutations interrupting PPPP. These features allow us to assert the high virulence of these strains. These findings reveal the circulation of low and high-virulence GaHV-2 strains in the Italian rural sector

A retrospective molecular study of select intestinal protozoa in healthy pet cats from Italy

The feline gut can harbour a number of protozoan parasites. Recent genetic studies have highlighted new epidemiological findings about species of Cryptosporidium, assemblages of Giardia duodenalis and Toxoplasma gondii. Furthermore, epidemiological studies suggest the occurrence of Tritrichomonas foetus in cats is on the increase worldwide. The prevalence of selected intestinal protozoa was determined by PCR using DNA previously extracted from the faeces of 146 privately owned healthy cats from Italy. Molecular genotyping on T gondii, G duodenalis and Cryptosporidium DNA was achieved. PCR assays were positive in 32 (22.9%) samples. Three animals (2.0%) were positive for T foetus and Cryptosporidium DNA, 15 specimens (10.3%) were positive for T gondii and 11 (7.5%) for G duodenalis. Co-infections were never observed. Results of the typing analysis allowed the identification of Cryptosporidium felis in all cases. The specimens positive for T gondii hinted at clonal genotype I (n = 7), genotype II (n = 1) and genotype III (n = 7). The G duodenalis isolates were referable to assemblages F (n = 9) and C (n = 2). In conclusion, the results obtained in this study add to the literature regarding the epidemiology of these parasites by confirming their presence in the faeces of healthy pet cats