3d printing and testing of rose thorns or limpet teeth inspired anchor device for tendon tissue repair

Purposes. Advancements in medical technology have enabled medical specialists to resolve significant problems concerning tendon injuries. However, despite the latest improvements, surgical tendon repair remains challenging. This study aims to explore the capabilities of the current state-of-the-art technologies for implantable devices. Methods. After performing extensive patent landscaping and literature review, an anchored tissue fixation device was deemed the most suitable candidate. This design was firstly investigated numerically, realizing a Finite Element Model of the device anchored to two swine tendons stumps, to simulate its application on a severed tendon. Two different hook designs, both bio-inspired, were tested while retaining the same device geometry and anchoring strategy. Then, the applicability of a 3D-printed prototype was tested on swine tendons. Finally, the device-tendon stumps ensemble was subjected to uniaxial tensile tests. Results. The results show that the investigated device enables a better load distribution during the immobilized limb period in comparison to standard suture-based approaches, yet it still presents several design flaws. Conclusions. The current implantable solutions do not ensure an optimal result in terms of strength recovery. This and other weak points of the currently available proposals will serve as a starting point for future works on bio-inspired implantable devices for tendon repair

Decreasing Prevalence of the Full Metabolic Syndrome but a Persistently High Prevalence of Dyslipidemia among Adult Arabs

A decade has passed since metabolic syndrome (MetS) was documented to be highly prevalent in the kingdom of Saudi Arabia. No follow-up epidemiologic study was done. This study aims to fill this gap. In this cross-sectional, observational study, a total of 2850 randomly selected Saudi adults aged 18–55 years were recruited. Subjects' information was generated from a database of more than 10,000 Saudi citizens from the existing Biomarkers Screening in Riyadh Program (RIYADH Cohort), Saudi Arabia. Anthropometrics included body mass index (BMI), blood pressure, as well as waist and hip circumferences. Fasting blood glucose and lipid profile were determined using routine laboratory procedures. The definition of ATP-III (NHANES III) was used for the diagnosis of the full MetS. The overall prevalence of complete MetS was 35.3% [Confidence-Interval (CI) 33.5–37.01]. Age-adjusted prevalence according to the European standard population is 37.0%. Low HDL-cholesterol was the most prevalent of all MetS risk factors, affecting 88.6% (CI 87.5–89.7) and hypertriglyceridemia the second most prevalent, affecting 34% (CI 32.3–35.7) of the subjects. The prevalence of the full MetS decreased from previous estimates but remains high, while dyslipidemia remains extremely high, affecting almost 90% of middle-aged Arabs. Screening for dyslipidemia among Saudi adults is warranted, especially among those most at risk. Scientific inquiry into the molecular causes of these manifestations should be pursued as a first step in the discovery of etiologic therapies

Synthesis and Anti-Mycobacterium tuberculosis Activity of Imidazo[2,1-b][1,3]oxazine Derivatives against Multidrug-Resistant Strains

The emergence of multidrug-resistant strains of M. tuberculosis has raised concerns due to the greater difficulties in patient treatment and higher mortality rates. Herein, we revisited the 2-nitro-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine scaffold and identified potent new carbamate derivatives having MIC90 values of 0.18–1.63 μM against Mtb H37Rv. Compounds 47–49, 51–53, and 55 exhibited remarkable activity against a panel of clinical isolates, displaying MIC90 values below 0.5 μM. In Mtb-infected macrophages, several compounds demonstrated a 1-log greater reduction in mycobacterial burden than rifampicin and pretomanid. The compounds tested did not exhibit significant cytotoxicity against three cell lines or any toxicity to Galleria mellonella. Furthermore, the imidazo[2,1-b][1,3]oxazine derivatives did not show substantial activity against other bacteria or fungi. Finally, molecular docking studies revealed that the new compounds could interact with the deazaflavin-dependent nitroreductase (Ddn) in a similar manner to pretomanid. Collectively, our findings highlight the chemical universe of imidazo[2,1-b][1,3]oxazines and their promising potential against MDR-TB

Expression of PROKR1 and PROKR2 in Human Enteric Neural Precursor Cells and Identification of Sequence Variants Suggest a Role in HSCR

Background The enteric nervous system (ENS) is entirely derived from neural crest and its normal development is regulated by specific molecular pathways. Failure in complete ENS formation results in aganglionic gut conditions such as Hirschsprung's disease (HSCR). Recently, PROKR1 expression has been demonstrated in mouse enteric neural crest derived cells and Prok-1 was shown to work coordinately with GDNF in the development of the ENS. Principal Findings In the present report, ENS progenitors were isolated and characterized from the ganglionic gut from children diagnosed with and without HSCR, and the expression of prokineticin receptors was examined. Immunocytochemical analysis of neurosphere-forming cells demonstrated that both PROKR1 and PROKR2 were present in human enteric neural crest cells. In addition, we also performed a mutational analysis of PROKR1, PROKR2, PROK1 and PROK2 genes in a cohort of HSCR patients, evaluating them for the first time as susceptibility genes for the disease. Several missense variants were detected, most of them affecting highly conserved amino acid residues of the protein and located in functional domains of both receptors, which suggests a possible deleterious effect in their biological function. Conclusions Our results suggest that not only PROKR1, but also PROKR2 might mediate a complementary signalling to the RET/GFRα1/GDNF pathway supporting proliferation/survival and differentiation of precursor cells during ENS development. These findings, together with the detection of sequence variants in PROKR1, PROK1 and PROKR2 genes associated to HSCR and, in some cases in combination with RET or GDNF mutations, provide the first evidence to consider them as susceptibility genes for HSCR.This work was supported by Fondo de Investigación Sanitaria, Spain (PI070080, PI1001290 and PI071315 for the E-Rare project), Consejería de Innovación Ciencia y Empresa de la Junta de Andalucía (CTS 2590) and Consejería de Salud de la Junta de Andalucía (PI0249-2008). The CIBER de Enfermedades Raras is an initiative of the ISCIII. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewe

Sialic Acid Glycobiology Unveils Trypanosoma cruzi Trypomastigote Membrane Physiology.

Trypanosoma cruzi, the flagellate protozoan agent of Chagas disease or American trypanosomiasis, is unable to synthesize sialic acids de novo. Mucins and trans-sialidase (TS) are substrate and enzyme, respectively, of the glycobiological system that scavenges sialic acid from the host in a crucial interplay for T. cruzi life cycle. The acquisition of the sialyl residue allows the parasite to avoid lysis by serum factors and to interact with the host cell. A major drawback to studying the sialylation kinetics and turnover of the trypomastigote glycoconjugates is the difficulty to identify and follow the recently acquired sialyl residues. To tackle this issue, we followed an unnatural sugar approach as bioorthogonal chemical reporters, where the use of azidosialyl residues allowed identifying the acquired sugar. Advanced microscopy techniques, together with biochemical methods, were used to study the trypomastigote membrane from its glycobiological perspective. Main sialyl acceptors were identified as mucins by biochemical procedures and protein markers. Together with determining their shedding and turnover rates, we also report that several membrane proteins, including TS and its substrates, both glycosylphosphatidylinositol-anchored proteins, are separately distributed on parasite surface and contained in different and highly stable membrane microdomains. Notably, labeling for α(1,3)Galactosyl residues only partially colocalize with sialylated mucins, indicating that two species of glycosylated mucins do exist, which are segregated at the parasite surface. Moreover, sialylated mucins were included in lipid-raft-domains, whereas TS molecules are not. The location of the surface-anchored TS resulted too far off as to be capable to sialylate mucins, a role played by the shed TS instead. Phosphatidylinositol-phospholipase-C activity is actually not present in trypomastigotes. Therefore, shedding of TS occurs via microvesicles instead of as a fully soluble form

Optimization of the lead probe neutron detector.

The lead probe neutron detector was originally designed by Spencer and Jacobs in 1965. The detector is based on lead activation due to the following neutron scattering reactions: {sup 207}Pb(n, n'){sup 207m}Pb and {sup 208}Pb(n, 2n){sup 207m}Pb. Delayed gammas from the metastable state of {sup 207m}Pb are counted using a plastic scintillator. The half-life of {sup 207m}Pb is 0.8 seconds. In the work reported here, MCNP was used to optimize the efficiency of the lead probe by suitably modifying the original geometry. A prototype detector was then built and tested. A 'layer cake' design was investigated in which thin (< 5 mm) layers of lead were sandwiched between thicker ({approx} 1 - 2 cm) layers of scintillator. An optimized 'layer cake' design had Figures of Merit (derived from the code) which were a factor of 3 greater than the original lead probe for DD neutrons, and a factor of 4 greater for DT neutrons, while containing 30% less lead. A smaller scale, 'proof of principle' prototype was built by Bechtel/Nevada to verify the code results. Its response to DD neutrons was measured using the DD dense plasma focus at Texas A&M and it conformed to the predicted performance. A voltage and discriminator sweep was performed to determine optimum sensitivity settings. It was determined that a calibration operating point could be obtained using a {sup 133}Ba 'bolt' as is the case with the original lead probe

Extragalactic Radio Continuum Surveys and the Transformation of Radio Astronomy

Next-generation radio surveys are about to transform radio astronomy by discovering and studying tens of millions of previously unknown radio sources. These surveys will provide new insights to understand the evolution of galaxies, measuring the evolution of the cosmic star formation rate, and rivalling traditional techniques in the measurement of fundamental cosmological parameters. By observing a new volume of observational parameter space, they are also likely to discover unexpected new phenomena. This review traces the evolution of extragalactic radio continuum surveys from the earliest days of radio astronomy to the present, and identifies the challenges that must be overcome to achieve this transformational change.Comment: To be published in Nature Astronomy 18 Sept 201

Significant and variable linear polarization during the prompt optical flash of GRB 160625B.

Newly formed black holes of stellar mass launch collimated outflows (jets) of ionized matter that approach the speed of light. These outflows power prompt, brief and intense flashes of γ-rays known as γ-ray bursts (GRBs), followed by longer-lived afterglow radiation that is detected across the electromagnetic spectrum. Measuring the polarization of the observed GRB radiation provides a direct probe of the magnetic fields in the collimated jets. Rapid-response polarimetric observations of newly discovered bursts have probed the initial afterglow phase, and show that, minutes after the prompt emission has ended, the degree of linear polarization can be as high as 30 per cent-consistent with the idea that a stable, globally ordered magnetic field permeates the jet at large distances from the central source. By contrast, optical and γ-ray observations during the prompt phase have led to discordant and often controversial results, and no definitive conclusions have been reached regarding the origin of the prompt radiation or the configuration of the magnetic field. Here we report the detection of substantial (8.3 ± 0.8 per cent from our most conservative simulation), variable linear polarization of a prompt optical flash that accompanied the extremely energetic and long-lived prompt γ-ray emission from GRB 160625B. Our measurements probe the structure of the magnetic field at an early stage of the jet, closer to its central black hole, and show that the prompt phase is produced via fast-cooling synchrotron radiation in a large-scale magnetic field that is advected from the black hole and distorted by dissipation processes within the jet

Neutron scattering effects on fusion ion temperature measurements.

To support the nuclear fusion program at Sandia National Laboratories (SNL), a consistent and verifiable method to determine fusion ion temperatures needs to be developed. Since the fusion temperature directly affects the width in the spread of neutron energies produced, a measurement of the neutron energy width can yield the fusion temperature. Traditionally, the spread in neutron energies is measured by using time-of-flight to convert a spread in neutron energies at the source to a spread in time at detector. One potential obstacle to using this technique at the Z facility at SNL is the need to shield the neutron detectors from the intense bremsstrahlung produced. The shielding consists of eight inches of lead and the concern is that neutrons will scatter in the lead, artificially broaden the neutron pulse width and lead to an erroneous measurement. To address this issue, experiments were performed at the University of Rochester's Laboratory for Laser Energetics, which demonstrated that a reliable ion temperature measurement can be achieved behind eight inches of lead shielding. To further expand upon this finding, Monte Carlo N-Particle eXtended (MCNPX) was used to simulate the experimental geometric conditions and perform the neutron transport. MCNPX was able to confidently estimate results observed at the University of Rochester