Cytotoxic screening and antibacterial activity of Withaferin A.

Cancer and bacterial infections are among the leading causes of death worldwide. Plant-derived bioactive compounds constitute promising alternatives for development of new therapeutics. This study aimed at evaluating the biological activity of Withaferin A using 6 tumor cell lines: A549 (lung cancer), U87MG (glioblastoma), SH-SY5Y (neuroblastoma), B16-F10 (mouse melanoma), HeLa (uterine colon cancer) and K562 (chronic myeloid leukemia). In addition, 17 other standard bacterial strains and several multidrug resistant bacteria (MDR) clinical isolates were examined. Cell viability was assessed using the following assays: MTT, neutral red, and dsDNA PicoGreen®. Further, oxidative stress was measured by quantification of reactive oxygen species (ROS) production. The activity against bacteria was determined by the minimum inhibitory concentration (MIC), minimum bacterial concentration (CBM) and antibiofilm activity in the production of strains. Withaferin A was effective, as evidenced by its cytotoxic activity in tumor cell lines, enhanced ROS production in tumor cells and bactericidal and antibiofilm activity. Data demonstrated that Withaferin A may be therapeutically considered as an antitumor and antibacterial agent.

Triangle Singularity as the Origin of the a_{1}(1420).

The COMPASS Collaboration experiment recently discovered a new isovector resonancelike signal with axial-vector quantum numbers, the a_{1}(1420), decaying to f_{0}(980)π. With a mass too close to and a width smaller than the axial-vector ground state a_{1}(1260), it was immediately interpreted as a new light exotic meson, similar to the X, Y, Z states in the hidden-charm sector. We show that a resonancelike signal fully matching the experimental data is produced by the decay of the a_{1}(1260) resonance into K^{*}(→Kπ)K[over ¯] and subsequent rescattering through a triangle singularity into the coupled f_{0}(980)π channel. The amplitude for this process is calculated using a new approach based on dispersion relations. The triangle-singularity model is fitted to the partial-wave data of the COMPASS experiment. Despite having fewer parameters, this fit shows a slightly better quality than the one using a resonance hypothesis and thus eliminates the need for an additional resonance in order to describe the data. We thereby demonstrate for the first time in the light-meson sector that a resonancelike structure in the experimental data can be described by rescattering through a triangle singularity, providing evidence for a genuine three-body effect.

Directed, Elliptic, and Higher Order Flow Harmonics of Protons, Deuterons, and Tritons in Au+Au Collisions at sqrt[s_{NN}]=2.4 GeV.

Flow coefficients v_{n} of the orders n=1-6 are measured with the High-Acceptance DiElectron Spectrometer (HADES) at GSI for protons, deuterons, and tritons as a function of centrality, transverse momentum, and rapidity in Au+Au collisions at sqrt[s_{NN}]=2.4 GeV. Combining the information from the flow coefficients of all orders allows us to construct for the first time, at collision energies of a few GeV, a multidifferential picture of the angular emission pattern of these particles. It reflects the complicated interplay between the effect of the central fireball pressure on the emission of particles and their subsequent interaction with spectator matter. The high precision information on higher order flow coefficients is a major step forward in constraining the equation of state of dense baryonic matter.

Use of synthetic cartilage implant (Cartiva®) for degeneration of the first and second metatarsophalangeal joint: what is the current evidence?

Polyvinyl alcohol hydrogel implants (also known as Synthetic Cartilage Implant or Cartiva® have been described in the treatment of degeneration of the first and second metatarsophalangeal joint (MTPJ). We reviewed literature to report characteristics of devices on the market and investigate their efficacy and safety. Following the PRISMA checklist, the Medline and Scopus databases were searched, including studies reporting use of Cartiva® for treating joint degeneration of the first and second MPTJ. Studies were searched for surgical technique, postoperative protocol, clinical scores, complications and reoperations. We found that, although some studies suggest that the use of Synthetic Cartilage Implant (Cartiva® is effective in the treatment of hallux rigidus in providing symptoms relief without sacrifice of joint motion, the redundancy of cohorts reported in studies and the frequency of conflict of interest reported by authors weaken the strength of evidence available and warrant further studies. Regarding the treatment of the second MTPJ ailments, no recommendation can be formulated to date due to the lack of primary studies.

New plates with polyaxial locking system and PSI technique in medial open wedge high tibial osteotomy: preliminary results.

Medial open-wedge (MOW) high tibial osteotomy (HTO) is proven treatment option, indicated in medial unicompartimental knee osteoarthritis (OA) and in varus OA. New devices and techniques were developed in last years, such as Activemotion plates with polyaxial locking system (Dualtec System®, NewClip-Technics) and PSI technique. We describe outcomes and rate of complications in patients treated with Activemotion plates and PSI technique. From January 2019 to August 2019 a sample of 77 cases (72 NCT plates, 5 PSI technique) was observed, evaluating the rate of complications and the return to activity. The rate of complications is 2.6% and the mean time to return to activity is 10 weeks. MOW HTO with Activemotion plate has showed good results with a low rate of complications. About PSI technique, the preliminary results are excellent, but we need to increase the sample.

Foot and ankle measurements on cone beam weightbearing computed tomography.

Over the last years, an increased number of studies have reported the use of cone beam weightbearing computed tomography (WBCT) in the assessment of foot and ankle pathology. This new technology has enabled to overcome the limits inherently related to two-dimensional radiographs (superimposition bias, operator-related bias, rotation bias) and to obtain images reproducing the bones and joints anatomy during physiological standing with a low radiation dose. We performed a review of the current literature to summarize the evidence about the use of 2D or 3D measurements on WBCT images in various foot and ankle conditions. Our aims were to describe measurements proposed so far and to report data on reliability and validity from primary authors.

Blood loss and transfusion rate in patients undergoing two-stage exchange in infected total knee arthroplasty.

Two-stage exchange in infected total knee arthroplasty is a reliable technique, but it has a high rate of blood loss. The study aims to compare the pre-operative and post-operative haemoglobin levels, the rate of transfusion, and the blood loss in two-stage exchange. From July 2018 to July 2019, eighteen patients underwent two-stage exchange of their infected total knee arthroplasty. Local and systemic tranexamic acid was administered in both surgical stages. Calculated blood loss was 2246 mL (range 1528 - 2850) in the first stage and 2388 mL (1873 - 2829) during reimplantation, respectively. The corresponding transfusion rate was 55 % and 67%, respectively. With the numbers available, these differences were not significant. In conclusion, this study shows that the blood loss and transfusion rate are similar during the two stages of exchange knee arthroplasty for infection.

Prevention and treatment of peri-prosthetic joint infection using surgical wound irrigation.

Over the past decade, the incidence of revision arthroplasty due to infection has increased substantially, often resulting in multiple surgical interventions with variable success rates and poor clinical outcome. Intraoperative wound irrigation has been proposed to reduce bacterial bioburden and contamination, but currently there is no widely accepted recommendation for the use of topical antiseptics, whether as separate molecules or as a mixed solution. We reviewed studies regarding the use of intraoperative topical antiseptics, their security profile and efficacy in preventing and treating infections of orthopedic implants and introduced a possible combination that may prove valuable in the future.

Severe obstructive sleep apnea is associated with circulating microRNAs related to heart failure, myocardial ischemia, and cancer proliferation.

PURPOSE: Obstructive sleep apnea (OSA) is associated with multiple comorbid conditions including cardiovascular diseases and cancer. There is a growing interest in exploring biomarkers to understand the related mechanisms and improve the risk stratification of OSA. Circulating microRNAs (miRNAs) are single noncoding strands of nearly 22 nucleotides that posttranscriptionally regulate target gene expression. Our aim was to identify miRNA profiles associated with OSA. METHODS: We studied 48 male subjects, mostly Caucasian (63%) and overweight, divided by polysomnography into the no OSA control group (n = 6), mild OSA group (n = 12), moderate OSA group (n = 15), and severe OSA group (n = 15). The study groups were matched for age, body mass index (BMI), and body fat composition. miRNA profiles were measured from peripheral whole blood using two steps: (1) microarray analysis comprising more than 2500 miRNAs in a subsample of 12 subjects (three from each group); and (2) validation phase using real-time quantitative polymerase chain reaction (RTqPCR). RESULTS: The microarray assessment identified 21 differentially expressed miRNAs among the groups. The RT-qPCR assessment showed that miR-1254 and miR-320e presented a gradual increase in expression parallel to OSA severity. Linear regression analysis showed that severe OSA was independently associated with miR-1254 (ß = 68.4; EP = 29.8; p = 0.02) and miR-320e (ß = 76.1; EP = 31.3; p = 0.02). CONCLUSION: Severe OSA is independently associated with miRNAs that are involved in heart failure (miR-1254), myocardial ischemia/reperfusion (miR-320e), and cell proliferation in some cancer types (miR-1254 and miR-320e). Future investigations addressing whether these miRs may provide prognostic information in OSA are needed.

Strong Absorption of Hadrons with Hidden and Open Strangeness in Nuclear Matter.

We present the first observation of K^{-} and ϕ absorption within nuclear matter by means of π^{-}-induced reactions on C and W targets at an incident beam momentum of 1.7 GeV/c studied with HADES at SIS18/GSI. The double ratio (K^{-}/K^{+})_{W}/(K^{-}/K^{+})_{C} is found to be 0.319±0.009(stat)_{-0.012}^{+0.014}(syst) indicating a larger absorption of K^{-} in heavier targets as compared to lighter ones. The measured ϕ/K^{-} ratios in π^{-}+C and π^{-}+W reactions within the HADES acceptance are found to be equal to 0.55±0.04(stat)_{-0.07}^{+0.06}(syst) and to 0.63±0.06(stat)_{-0.11}^{+0.11}(syst), respectively. The similar ratios measured in the two different reactions demonstrate for the first time experimentally that the dynamics of the ϕ meson in nuclear medium is strongly coupled to the K^{-} dynamics. The large difference in the ϕ production off C and W nuclei is discussed in terms of a strong ϕN in-medium coupling. These results are relevant for the description of heavy-ion collisions and the structure of neutron stars.

Self-assembled materials and supramolecular chemistry within microfluidic environments: from common thermodynamic states to non-equilibrium structures.

Self-assembly is a crucial component in the bottom-up fabrication of hierarchical supramolecular structures and advanced functional materials. Control has traditionally relied on the use of encoded building blocks bearing suitable moieties for recognition and interaction, with targeting of the thermodynamic equilibrium state. On the other hand, nature leverages the control of reaction-diffusion processes to create hierarchically organized materials with surprisingly complex biological functions. Indeed, under non-equilibrium conditions (kinetic control), the spatio-temporal command of chemical gradients and reactant mixing during self-assembly (the creation of non-uniform chemical environments for example) can strongly affect the outcome of the self-assembly process. This directly enables a precise control over material properties and functions. In this tutorial review, we show how the unique physical conditions offered by microfluidic technologies can be advantageously used to control the self-assembly of materials and of supramolecular aggregates in solution, making possible the isolation of intermediate states and unprecedented non-equilibrium structures, as well as the emergence of novel functions. Selected examples from the literature will be used to confirm that microfluidic devices are an invaluable toolbox technology for unveiling, understanding and steering self-assembly pathways to desired structures, properties and functions, as well as advanced processing tools for device fabrication and integration.

A role for astrocytes in cerebellar deficits in frataxin deficiency: Protection by insulin-like growth factor I.

Inherited neurodegenerative diseases such as Friedreich's ataxia (FRDA), produced by deficiency of the mitochondrial chaperone frataxin (Fxn), shows specific neurological deficits involving different subset of neurons even though deficiency of Fxn is ubiquitous. Because astrocytes are involved in neurodegeneration, we analyzed whether they are also affected by frataxin deficiency and contribute to the disease. We also tested whether insulin-like growth factor I (IGF-I), that has proven effective in increasing frataxin levels both in neurons and in astrocytes, also exerts in vivo protective actions. Using the GFAP promoter expressed by multipotential stem cells during development and mostly by astrocytes in the adult, we ablated Fxn in a time-dependent manner in mice (FGKO mice) and found severe ataxia and early death when Fxn was eliminated during development, but not when deleted in the adult. Analysis of underlying mechanisms revealed that Fxn deficiency elicited growth and survival impairments in developing cerebellar astrocytes, whereas forebrain astrocytes grew normally. A similar time-dependent effect of frataxin deficiency in astrocytes was observed in a fly model. In addition, treatment of FGKO mice with IGF-I improved their motor performance, reduced cerebellar atrophy, and increased survival. These observations indicate that a greater vulnerability of developing cerebellar astrocytes to Fxn deficiency may contribute to cerebellar deficits in this inherited disease. Our data also confirm a therapeutic benefit of IGF-I in early FRDA deficiency.

Occurrence of mycotoxins in talkan: a cereal-based food traditional for Turkic population.

The consumption of cereal contaminated with mycotoxins poses a serious health risk for humans and animals. The present work aims to evaluate the presence of mycotoxins in talkan, a cereal-based food commonly consumed by the Turkic population. The presence of mycotoxins was investigated in a total of 50 samples obtained from Kazakhstan. After a preliminary screening using various ELISA kits, mycotoxins were confirmed and quantified by HPLC-MS/MS method. More than 28% of the samples were positive for at least one mycotoxin. The calculated probably daily intake for adults and children was 20% above the tolerable daily intake for aflatoxin B1 and deoxynivalenol, while it was above 100% for zearalenone, indicating a high risk for the Kazakh population. A total of 12 samples exhibited concentrations above the European maximum level for ochratoxin A, zearalenone and deoxynivalenol, however, these values were within the limits established by the Russia-Kazakhstan-Belarus Customs Union (TR CU 015/2011).

The autoimmunity-associated gene RGS1 affects the frequency of T follicular helper cells.

RGS1 (regulator of G-protein signaling 1) has been associated with multiple autoimmune disorders including type I diabetes. RGS1 desensitizes the chemokine receptors CCR7 and CXCR4 that are critical to the localization of T and B cells in lymphoid organs. To explore how RGS1 variation contributes to autoimmunity, we generated Rgs1 knockdown (KD) mice in the nonobese diabetic (NOD) model for type I diabetes. We found that Rgs1 KD increased the size of germinal centers, but decreased the frequency of T follicular helper (TFH) cells. We show that loss of Rgs1 in T cells had both a T cell-intrinsic effect on migration and TFH cell frequency, and an indirect effect on B-cell migration and germinal center formation. Notably, several recent publications described an increase in circulating TFH cells in patients with type I diabetes, suggesting this cell population is involved in pathogenesis. Though Rgs1 KD was insufficient to alter diabetes frequency in the NOD model, our findings raise the possibility that RGS1 plays a role in autoimmunity owing to its function in TFH cells. This mechanistic link, although speculative at this time, would lend support to the notion that TFH cells are key participants in autoimmunity and could explain the association of RGS1 with several immune-mediated diseases.

Nonclassicality Criteria in Multiport Interferometry.

Interference lies at the heart of the behavior of classical and quantum light. It is thus crucial to understand the boundaries between which interference patterns can be explained by a classical electromagnetic description of light and which, on the other hand, can only be understood with a proper quantum mechanical approach. While the case of two-mode interference has received a lot of attention, the multimode case has not yet been fully explored. Here we study a general scenario of intensity interferometry: we derive a bound on the average correlations between pairs of output intensities for the classical wavelike model of light, and we show how it can be violated in a quantum framework. As a consequence, this violation acts as a nonclassicality witness, able to detect the presence of sources with sub-Poissonian photon-number statistics. We also develop a criterion that can certify the impossibility of dividing a given interferometer into two independent subblocks.

Pathogen and Particle Associations in Wastewater: Significance and Implications for Treatment and Disinfection Processes.

Disinfection guidelines exist for pathogen inactivation in potable water and recycled water, but wastewater with high numbers of particles can be more difficult to disinfect, making compliance with the guidelines problematic. Disinfection guidelines specify that drinking water with turbidity ≥1 Nephelometric Turbidity Units (NTU) is not suitable for disinfection and therefore not fit for purpose. Treated wastewater typically has higher concentrations of particles (1-10NTU for secondary treated effluent). Two processes widely used for disinfecting wastewater are chlorination and ultraviolet radiation. In both cases, particles in wastewater can interfere with disinfection and can significantly increase treatment costs by increasing operational expenditure (chemical demand, power consumption) or infrastructure costs by requiring additional treatment processes to achieve the required levels of pathogen inactivation. Many microorganisms (viruses, bacteria, protozoans) associate with particles, which can allow them to survive disinfection processes and cause a health hazard. Improved understanding of this association will enable development of cost-effective treatment, which will become increasingly important as indirect and direct potable reuse of wastewater becomes more widespread in both developed and developing countries. This review provides an overview of wastewater and associated treatment processes, the pathogens in wastewater, the nature of particles in wastewater and how they interact with pathogens, and how particles can impact disinfection processes.

Assessment of food safety using a new real-time PCR assay for detection and quantification of virulence factors of enterococci in food samples.

AIMS: Development of Taqman MGB real-time PCR (q-PCR) assays for the quantitative detection of virulence factor genes in pure culture and food samples with regard to food safety assessment. METHODS AND RESULTS: New Taqman primers and probes were designed for the ace, esp and gelE genes based on the determinants of virulence profiles of enterococcal strains from GenBank. The high specificity and accuracy of the Taqman probe assay was confirmed. The limit of detection for the different virulence genes was 102  CFU ml-1 or CFU g-1 for pure culture and meat samples, and 103  CFU g-1 for cheese samples. CONCLUSION: This method provides the specific and rapid detection and quantification of ace, esp and gelE genes compared to conventional PCR assays, thus allowing the rapid and direct safety assessment of Enterococcus genus in food samples. SIGNIFICANCE AND IMPACT OF THE STUDY: This study presents efficient methods that can be used directly on food products for the rapid quantification and tracing of virulence genes, regarding food safety assessment. Moreover, this is the first study to quantify these virulence factors using a specific Taqman q-PCR assay in food samples.

Development of a real-time PCR assay for direct detection and quantification of Bacillus sporothermodurans in ultra-high temperature milk.

In our study, a new and highly sensitive real-time PCR Taqman assay was developed for the direct and specific detection of Bacillus sporothermodurans in UHT milk. The target region was selected based on the 16S rRNA gene profiles of 11 B. sporothermodurans from GenBank. A standard curve was created using a reference strain of B. sporothermodurans, DSM 10599. A low limit of detection for B. sporothermodurans in UHT milk (10 cfu/mL) was obtained. Furthermore, a total of 110 UHT milk samples from several supermarkets were directly assessed to detect and quantify B. sporothermodurans using the real-time PCR Taqman developed. The B. sporothermodurans counts obtained were highly correlated with the microbial plate counts in the UHT milk samples. This is the first time that B. sporothermodurans has been quantified directly from UHT milk. This technique could be applicable as a routine tool for preventing the growth of these bacteria by allowing for the rapid screening of raw milk samples in dairy plants. As expected, the probability of bacterial growth in UHT milk packages increased with the B. sporothermodurans counts in the raw milk.

A study on toxic and essential elements in rice from the Republic of Kazakhstan: comparing the level of contamination in rice from the European Community.

Selected toxic elements (total As, Cd, Cr, Hg, Pb, Sr, U and V) and essential elements (Co, Cu, Fe, Mn and Zn) were analyzed using an inductively coupled plasma mass spectrometry (ICP-MS) in unpolished and milled rice collected from Kazakhstan and milled rice from Spain and Portugal to evaluate the potential health risk to the population. Arsenic species (arsenite, arsenate, arsenobetaine, dimethylarsinate and monomethilarsonate) were analyzed using HPLC-IC-MS. From 146 samples analyzed, none of them exceeded the maximum limit set by the European Legislation for Cd or Pb or values recommended by the Codex Alimentarius. Concentrations of Sr, U and V were below LOD and those of Hg, Pb, Co and Cr between

Experimental realization of a one-way quantum computer algorithm solving Simon's problem.

We report an experimental demonstration of a one-way implementation of a quantum algorithm solving Simon's problem-a black-box period-finding problem that has an exponential gap between the classical and quantum runtime. Using an all-optical setup and modifying the bases of single-qubit measurements on a five-qubit cluster state, key representative functions of the logical two-qubit version's black box can be queried and solved. To the best of our knowledge, this work represents the first experimental realization of the quantum algorithm solving Simon's problem. The experimental results are in excellent agreement with the theoretical model, demonstrating the successful performance of the algorithm. With a view to scaling up to larger numbers of qubits, we analyze the resource requirements for an n-qubit version. This work helps highlight how one-way quantum computing provides a practical route to experimentally investigating the quantum-classical gap in the query complexity model.