Antineuropathic and Antinociceptive Drugs Combination in Patients with Chronic Low Back Pain: A Systematic Review

Purpose. Chronic low back pain (LBP) is often characterized by both nociceptive and neuropathic components. While various monotherapies have been reported of only limited efficacy, combining drugs with different mechanisms of action and targets appears a rational approach. Aim of this systematic review is to assess the efficacy and safety of different combined pharmacological treatments, compared to monotherapy or placebo, for the pharmacological treatment of chronic LBP. Methods. Published papers, written or abstracted in English from 1990 through 2011, comparing combined pharmacological treatments of chronic LBP to monotherapy or placebo were reviewed. Results. Six articles met the inclusion criteria. Pregabalin combined with celecoxib or opioids was shown to be more effective than either monotherapy. Oxycodone-paracetamol versus previous treatments and tramadol-paracetamol versus placebo were also reported as effective, while morphine-nortriptyline did not show any benefit over any single agent. Conclusions. In spite of theoretical advantages of combined pharmacological treatments of chronic LBP, clinical studies are remarkably few. Available data show that combined therapy, including antinociceptive and antineuropathic agents is more effective than monotherapy, with similar side effects

Analysis of bovine intramammary bacteriome, resistome and of the bacterial transmission within dairy herds

Mastitis is the most important and costly disease in dairy cows worldwide. Bovine intramammary infection (IMI) caused by pathogenic bacteria is common and well understood but very little is known about the bacteria and their resistome present in the mammary gland (= intramammary resistome, IR) of healthy and untreated cows whose milk is regularly delivered for human consumption. The aim that our research project wanted to: i) describe the bacteriome of healthy cows means all the bacteria that we can isolate from the milk of healthy cow, ii) describe the resistome means the antibiotic resistance correlated with the bacteriome isolated with the use of phenotypic and genomic methods iii) comparison of the bacteriome and resistome with the environmental isolates. Healthy, untreated cows of nine dairy herds from the Swiss Canton Tessin were analyzed three times within one year to identify the most abundant species of the intramammary bacteriome of healthy animals. Aseptically collected milk samples were cultured and bacteria identified using MALDI-TOF mass spectrometry. To describe the intramammary resistome, 350 strains of the predominant species were selected and subjected to short-read based whole genome sequencing (WGS) combined with phenotypic analyses and antibiotic resistance gene profiling. Both chromosomes and mobile genetic elements were examined for antibiotic resistance genes (ARGs) using in-house and online software tools. ARGs were then associated with phenotypic antibiotic resistance profiling data from minimum inhibitory concentration assays. Furthermore, the phylogeny of the two main species isolated Staphylococcus xylosus (S. xylosus) and Mammaliicoccus sciuri (M. sciuri) was assessed using 70 housekeeping genes and the maximum likelihood approach (PhyML). Additionally statistical analyses were carried out. Of 256 cows (1024 single quarters) analyzed, 96% were bacteriologically positive and 80% of the quarters were positive for at least one bacterial species. 84.5% of the quarters were healthy with somatic cell counts (SCC) < 200’000 cells/ml, whereas 15.5% of the quarters showed a subclinical mastitis (SCC ≥ 200’000 cells/ml). The 1288 isolates were assigned to 104 different bacterial species including 24 predominant species. Staphylococcaceae were most prevalent (14 different species; 73.5% bacteria-positive quarters) with S. xylosus and M. sciuri accounting for 41.5% of the strains. Our study demonstrates that Staphylococcaceae could be consider part of the healthy milk bacteriome. Furthermore, the different farm-specific patterns of the bacteriome are associated with the use of different bedding in the herd. The non-aureus staphylococci and mammalicocci (NASM) have been regarded as minor mastitis pathogens being the most abundantly observed bacteria in mastitis milk samples. Based on our study, however, their function needs to be reconsidered. We could assume that different subtypes of NASM may colonize the mammary gland whereas other subtypes may cause minor mastitis. Phenotypic and genomic antimicrobial resistance (AMR) was bacterium-specific whereby resistance to clindamycin and oxacillin was most frequently observed (40% and 30%). In contrast, AMR to penicillin, although massively used for mastitis treatment during last decades, was rarely observed. The phenotypic findings, not in all the cases, could be linked to chromosomal or plasmid-borne ARGs, demonstrating a lack in understanding the mechanisms that lead to the observed phenotypic AMRs in the isolated bacteria. For some species/AMR, the observed phenotypic AMR could be explained. This is true for M. sciuri and its resistance to clindamycin (salA gene) as well as S. xylosus, M. sciuri and a few other bacteria in the case of tetracycline. For all of them, a small plasmid was found carrying the tetK or another tetracycline ARG. The presence of tetracycline AMR was herd dependent and was observed in various isolates of the same farm indicating a possible horizontal gene transfer among the different bacteria on the same farm, particularly among S. xylosus and M. sciuri. The phylogenetic studies involved S. xylosus and M. sciuri; these bacteria were the most abundant isolated and were collected from both milk and environmental samples. M. sciuri was found predominantly in environmental samples (particularly straw bedding and teat liners before milking). Differently, the S. xylosus strains were mostly isolated from milk samples. Based on these results we could conclude that S. xylosus is mainly udder adapted whereas the habitat of M. sciuri is more environmentally related. Detailed phylogenetic analyses for M. sciuri revealed two main clades whereby the smaller one included the M. sciuri type strain. Typically, the strains forming this clade were almost exclusively isolated from bedding, milk, and teats, whereas those of the other clade were isolated from milk, teats, and liners, but hardly from bedding. These results suggest that M. sciuri circulates clade dependently more among environment and mammary gland (type strain clade) whereas M. sciuri of the other clade circulates more among mammary gland and milking equipment. These findings are confirmed by genotype analysis, inferring MLST, demonstrating that the distribution of the sequence types (STs) between milk and environment revealed only a few common STs. Interestingly, M. sciuri showed a remarkable variability at the STs level with the consequence that a number of different STs were observed on the same farm. In the case of S. xylosus, three main clades were observed. As in M. sciuri, the phylogenetic distances within each clade were very small showing that the taxa/strains evolved minimally and that they are genetically very similar. For all three clades, the taxa were largely milk associated whereas environmental taxa were hardly observed. These findings indicate that S. xylosus circulates primarily among mammary glands and the taxa found in the environment are more the result of a contamination by milk. As a conclusion, the research project demonstrates that bacteria, particularly NASM, are very common in the mammary gland of healthy cows, a fact that needs to be considered when interpreting bacteriological results obtained from clinical milk samples. Furthermore, AMR in NASM is uncommon, also against penicillin, although it has been massively used for mastitis treatment during last decades. Unfortunately, AMR in these bacteria remains largely unexplained by genomic analyses. Furthermore, AMR against antibiotics used in human medicine is rare. Finally, phylogenetic studies demonstrate that M. sciuri and S. xylosus formed only a few major clades and within each clade the strains were genetically very similar; for M. sciuri the habitat was clade dependent. It is essential to get more knowledge about the bacteriome of the mammary glands of healthy and diseased cows to understand the microbiota, hinder pathogens to gain a foothold and, in the long term, prevent the development and spread of resistances. WGS represents an important tool for detecting ARGs but still needs to be associated with phenotypic analysis and with gene and/or protein expression analyses. Screening for new genes associated with AMR and an increase of the ARG databases will be essential, especially for the One Health concept

Применение имплантатов с антибактериальным покрытием в ортопедии и травматологии: современное состояние проблемы

Current prophylactic and hygienic measures notwithstanding, implant-related infection remains among leading reasons for failure in orthopaedics and trauma surgery, resulting in extremely high social and economic costs. Various antibacterial coating technologies have been proven safe and effective both in preclinical and in clinical settings and able to reduce post-surgical infections up to 90%, depending on the type of the coating and on the experimental setup. In spite of this findings, the widespread use of these technologies is still limited by several factors. After reviewing the latest evidence on currently available antibacterial coatings, an algorithm is proposed to calculate the impact of the delayed introduction of these technologies in the clinical practice. When applied to joint arthroplasties, our calculator shows that each year of delay to implement an antibacterial coating, able to reduce post-surgical infection by 80% at a final user’s cost price of €600, causes an estimated 35 200 new cases of periprosthetic joint infection in Europe and additional annual hospital costs of approximately €440 million. Faster and more affordable regulatory pathways for antibacterial coating technologies and an adequate reimbursement policy for their clinical use appear a feasible solution to mitigate the impact of implant-related infections and may benefit patients, healthcare systems, and related research.All patients provided written informed consent.Competing interests: the authors declare that there are no competing interests.Несмотря на современные достижения профилактики и гигиены, имплант-ассоциированная инфекция остается одной из основных причин несостоятельных результатов ортопедических и травматологических вмешательств, что приводит к чрезвычайно высоким социальным и экономическим издержкам. Различные технологии антибактериального покрытия имплантатов зарекомендовали себя как безопасное и эффективное решение проблемы инфицирования в процессе как доклинических исследований, так и в клинической практике, что способствует снижению частоты послеоперационной инфекции до 90% в зависимости от типа покрытия и условий использования. Несмотря на такие выводы, широкое внедрение подобных технологий по-прежнему ограничено несколькими факторами. Изучив наиболее актуальные данные по доступным антибактериальным покрытиям, авторы предлагают алгоритм для расчета влияния несвоевременного внедрения таких технологий в клиническую практику. Применение предлагаемого калькулятора к операциям по эндопротезированию суставов демонстрирует, что каждый год отсрочки внедрения антибактериальных покрытий, который позволил бы снизить частоту послеоперационной инфекции на 80% при стоимости для конечного пользователя в размере 600 евро, приведет примерно к 35 200 новых случаев возникновения перипротезной инфекции в странах Европы и к дополнительным ежегодным госпитальным расходам в размере около 440 млн евро. Ускоренные и более доступные с точки зрения затрат процессы нормативного регулирования в отношении технологий антибактериального покрытия имплантатов, а также адекватная политика возмещения расходов по клиническому использованию таких технологий представляются возможным решением для снижения частоты имплант-ассоциированной инфекции, улучшения качества лечения пациентов, снижения нагрузки на систему здравоохранения и для стимулирования научных изысканий

Heat Transfer across the Free Surface of a Thermocapillary Liquid Bridge

The heat transfer across the free surface of a millimetric thermocapillary liquid bridge is investigated for two dimensional axisymmetric flows, computed by Newton–Raphson iteration. The coupled multiphase flow in the silicone-oil liquid bridge and in the ambient gas (air) is considered for Marangoni and Prandtl numbers of interest for typical space experiments. Based on the space-resolved heat flux of the two-phase flow for a wide range of parameters, we derive a model for the heat flux in form of Newton’s heat transfer law for a surrogate single phase flow, in which a space-dependent Biot function is considered. A parametric study for a 2 St silicone-oil liquid bridge is conducted for 150 configurations to derive a reliable fit of the Biot function for a wide range of Reynolds numbers and aspect ratios. An explicit form of the parametric fit is provided which takes into account the hot- and cold-wall boundary layers in the liquid

Two-bands effect on the superconducting fluctuating diamagnetism in MgB&#8322

The field dependence of the magnetization above the transition temperature Tc in MgB&#8322; is shown to evidence a diamagnetic contribution consistent with superconducting fluctuations reflecting both the &#963; and &#960; bands. In particular, the upturn field Hup in the magnetization curve, related to the incipient effect of the magnetic field in quenching the fluctuating pairs, displays a double structure, in correspondence to two correlation lengths. The experimental findings are satisfactorily described by the extension to the diamagnetism of a recent theory for paraconductivity, in the framework of a zero-dimensional model for the fluctuating superconducting droplets above Tc

Particle accumulation in high‐Prandtl‐number liquid bridges

Particle accumulation in high‐Prandtl‐number (Pr = 68) thermocapillary liquid bridges is studied numerically. Randomly distributed small rigid non‐interacting spherical particles are found to cluster in particle accumulation structures. The accumulation is found to be caused by a finite‐particle‐size effect when the particles move close to the impermeable flow boundaries. The extra drag force experienced by a particle near the boundaries creates a dissipation in the dynamical system describing the particle motion. This causes particles to be attracted to regions in or near Kolmogorov‐Arnold‐Moser tori of the unperturbed flow field.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153263/1/pamm201900058.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/153263/2/pamm201900058_am.pd