A review of the current evidence of fruit phenolic compounds as potential antimicrobials against pathogenic bacteria.

Fruits are among the main natural sources of phenolic compounds (PC). These compounds exert important antioxidant properties primarily associated with the presence of hydroxyl groups in their molecular structure. Additionally, the antibacterial effects of fruit phenolic-rich extracts or individual PC commonly found in fruits have been an emerging research focus in recent years. This review discusses by first time the available literature regarding the inhibitory effects of fruit PC on pathogenic bacteria, including not only their direct effects on bacterial growth and survival, but also their effects on virulence factors and antibiotic resistance, as well as the possible mechanism underlying these inhibitory properties. The results of the retrieved studies show overall that the antibacterial effects of fruit PC vary with the target bacteria, type of PC and length of exposure to these compounds. The type of solvent and procedures used for extraction and fruit cultivar also seem to influence the antibacterial effects of phenolic-rich fruit extracts. Fruit PC have shown wide-spectrum antibacterial properties besides being effective antibiotic resistance modifying agents in pathogenic bacteria and these effects have shown to be associated with interruption of efflux pump expression/function. Furthermore, fruit PC can cause down regulation of a variety of genes associated with virulence features in pathogenic bacteria. Results of available studies indicate the depolarization and alteration of membrane fluidity as mechanisms underlying the inhibition of pathogenic bacteria by fruit PC. These data reveal fruit PC have potential antimicrobial properties, which should be rationally exploited in solutions to control pathogenic bacteria.

Intraspecific and interspecific variation in thermotolerance and photoacclimation in Symbiodinium dinoflagellates.

Light and temperature are major drivers in the ecology and biogeography of symbiotic dinoflagellates living in corals and other cnidarians. We examined variations in physiology among 11 strains comprising five species of clade A Symbiodinium We grew cultures at 26°C (control) and 32°C (high temperature) over a duration of 18 days while measuring growth and photochemical efficiency (Fv /Fm ). Responses to thermal stress ranged from susceptible to tolerant across species and strains. Most strains exhibited a decrease in cell densities and Fv /Fm when grown at 32°C. Tolerance to high temperature (T32) was calculated for all strains, ranging from 0 (unable to survive at high temperature) to 1 (able survive at high temperature). There was substantial variation in thermotolerance across species and among strains. One strain had a T32 close to 1, indicating that growth was not reduced at 32°C for only this one strain. To evaluate the combined effect of temperature and light on physiological stress, we selected three strains with different levels of thermotolerance (tolerant, intermediate and susceptible) and grew them under five different light intensities (65, 80, 100, 240 and 443 µmol quanta m-2 s-1) at 26 and 32°C. High irradiance exacerbated the effect of high temperature, particularly in strains from thermally sensitive species. This work further supports the recognition that broad physiological differences exist not only among species within Symbiodinium clades, but also among strains within species demonstrating that thermotolerance varies widely between species and among strains within species.

Tomographic diffractive microscopy with agile illuminations for imaging targets in a noisy background.

Tomographic diffractive microscopy is a marker-free optical digital imaging technique in which three-dimensional samples are reconstructed from a set of holograms recorded under different angles of incidence. We show experimentally that, by processing the holograms with singular value decomposition, it is possible to image objects in a noisy background that are invisible with classical wide-field microscopy and conventional tomographic reconstruction procedure. The targets can be further characterized with a selective quantitative inversion.

Scoping review of the recommendations and guidance for improving the quality of rare disease registries.

BACKGROUND: Rare disease registries (RDRs) are valuable tools for improving clinical care and advancing research. However, they often vary qualitatively, structurally, and operationally in ways that can determine their potential utility as a source of evidence to support decision-making regarding the approval and funding of new treatments for rare diseases. OBJECTIVES: The goal of this research project was to review the literature on rare disease registries and identify best practices to improve the quality of RDRs. METHODS: In this scoping review, we searched MEDLINE and EMBASE as well as the websites of regulatory bodies and health technology assessment agencies from 2010 to April 2023 for literature offering guidance or recommendations to ensure, improve, or maintain quality RDRs. RESULTS: The search yielded 1,175 unique references, of which 64 met the inclusion criteria. The characteristics of RDRs deemed to be relevant to their quality align with three main domains and several sub-domains considered to be best practices for quality RDRs: (1) governance (registry purpose and description; governance structure; stakeholder engagement; sustainability; ethics/legal/privacy; data governance; documentation; and training and support); (2) data (standardized disease classification; common data elements; data dictionary; data collection; data quality and assurance; and data analysis and reporting); and (3) information technology (IT) infrastructure (physical and virtual infrastructure; and software infrastructure guided by FAIR principles (Findability; Accessibility; Interoperability; and Reusability). CONCLUSIONS: Although RDRs face numerous challenges due to their small and dispersed populations, RDRs can generate quality data to support healthcare decision-making through the use of standards and principles on strong governance, quality data practices, and IT infrastructure.

Gyrate atrophy of the choroid and retina: Update on diagnosis and treatment.

Gyrate atrophy of the choroid and retina (GACR) is a rare autosomal recessive disease characterised by elevated plasma ornithine levels due to deficiency of the enzyme ornithine aminotransferase (OAT). The accumulation of this amino acid in plasma leads to the development of patches of chorioretinal atrophy in the peripheral retina extending into the macular area. Patients usually present with night blindness followed by constriction of the visual field and, finally, decreased central vision and blindness. The disease is diagnosed by the presence of the characteristic clinical picture, the presence of hyperornithinaemia in plasma and the detection of mutations in the OAT enzyme gene. There is currently no effective gene therapy and the most common therapeutic intervention mainly involves dietary modifications with arginine restriction. This article aims to summarise the pathogenesis, clinical and diagnostic findings and treatment options in patients with GACR.

Proximal balloon-guided catheter with flow inversion vs. distal filter protection during the carotid stent placement, a seven years experience in a Colombian reference center.

BACKGROUND AND PURPOSE: The carotid stent placement as a therapeutic option for carotid stenosis has been increasing among years; therefore, studies are required to evaluate the security and efficacy of its materials. The purpose of this study was to evaluate the distal filter and the proximal balloon-guided catheter with flow inversion as protection devices during carotid angioplasty and stenting. METHODS: This is a retrospective, observational study of patients diagnosed with carotid stenosis treated with angioplasty between January 1, 2014, and June 30, 2020; we analyzed a radiology service database to compare the distal filter and the proximal balloon-guided catheter as protection devices during angioplasty. RESULTS: One hundred seventy-five angioplasties were performed, the distal filter was the most prevalent embolic protection device used (66%), patients baseline characteristics did not differ between groups with different embolic protection devices, except for history of dyslipidemia (p < 0.000). As well, we did not find any significant differences between the groups in the device related complications, intervention time (p = 0.140), unrelated complications (p = 0.693) and functional independence at 90 days (p = 0.096). CONCLUSIONS: In our study the proximal balloon-guided catheter and the distal filter protection device as protection devices during the carotid stenting didn't show significant differences regarding complications related to the system.

Characterization of mechanical properties of a hollow cylinder with zero group velocity Lamb modes.

Hollow cylinders used in the industry must be regularly inspected. Elastic guided waves, similar to Lamb modes in a plate, can propagate in the axial direction or around the circumference. They are sensitive to geometrical and mechanical parameters of the cylindrical shell. The objective of this paper is to show that zero group velocity (ZGV) Lamb modes can be used to bring out anisotropy and to measure elastic constants of the material. This study provides experimental and numerical investigations on a Zirconium alloy tube extensively used by the nuclear industry in reactor core components. A non-contact method, based on laser ultrasound techniques and ZGV Lamb modes, demonstrates that the difference observed between axial and circumferential guided waves cannot be explained by an isotropic model. Then, a transverse isotropic model is used for the Zircaloy tube. Four of the five elastic constants are directly extracted from ZGV resonance frequencies. The last one is deduced from the measured dispersion spectra. With this complete set of constants, a good agreement is obtained between theoretical and experimental dispersion curves for both axially and circumferentially propagating guided waves.

Real-time 3D imaging with Fourier-domain algorithms and matrix arrays applied to non-destructive testing.

Real-time 3D ultrasound imaging with matrix arrays remains a challenge in Non-Destructive Testing (NDT) due to the time-consuming reconstruction algorithms based on delay-and-sum operations. Other algorithms operating in the Fourier domain have lower algorithmic complexities and therefore higher frame rates at the cost of more storage space, which may limit the number of reconstruction points. In this paper, we present an implementation for real-time 3D imaging of the Total Focusing Method (TFM) and the Plane Wave Imaging (PWI), as well as of their Fourier-domain counterparts, referred to as k-TFM and k-PWI. For both types of acquisition, the Fourier-domain algorithms are used to increase frame rates, and they are compared to the time-domain TFM and PWI in terms of image quality, frame rates and memory requirements. In order to greatly reduce their memory requirements, a new implementation of k-TFM and k-PWI is proposed. The four imaging methods are then evaluated by imaging in real time a block of stainless steel containing a 3D network of spherical porosities produced by additive layer manufacturing using a powder bed laser fusion process.

Accelerated Alzheimer-type phenotype in transgenic mice carrying both mutant amyloid precursor protein and presenilin 1 transgenes.

Genetic causes of Alzheimer's disease (AD) include mutations in the amyloid precursor protein (APP), presenilin 1 (PS1), and presenilin 2 (PS2) genes. The mutant APP(K670N,M671L) transgenic line, Tg2576, shows markedly elevated amyloid beta-protein (A beta) levels at an early age and, by 9-12 months, develops extracellular AD-type A beta deposits in the cortex and hippocampus. Mutant PS1 transgenic mice do not show abnormal pathology, but do display subtly elevated levels of the highly amyloidogenic 42- or 43-amino acid peptide A beta42(43). Here we demonstrate that the doubly transgenic progeny from a cross between line Tg2576 and a mutant PS1M146L transgenic line develop large numbers of fibrillar A beta deposits in cerebral cortex and hippocampus far earlier than their singly transgenic Tg2576 littermates. In the period preceding overt A beta deposition, the doubly transgenic mice show a selective 41% increase in A beta42(43) in their brains. Thus, the development of AD-like pathology is substantially enhanced when a PS1 mutation, which causes a modest increase in A beta42(43), is introduced into Tg2576-derived mice. Remarkably, both doubly and singly transgenic mice showed reduced spontaneous alternation performance in a "Y" maze before substantial A beta deposition was apparent. This suggests that some aspects of the behavioral phenotype in these mice may be related to an event that precedes plaque formation.

Edge resonance and zero group velocity Lamb modes in a free elastic plate.

The local resonances of a free isotropic elastic plate are investigated using laser ultrasonic techniques. Experimental results are interpreted in terms of zero group velocity Lamb modes and edge mode. At a distance from the edge larger than the plate thickness a sharp resonance is observed at the frequency where the group velocity of the first symmetrical Lamb mode vanishes. Close to the edge of the plate, the resonance due to the edge mode dominates. Both zero group velocity and edge resonances appear at the theoretically predicted frequencies. These frequencies do not vary with the distance from the edge of the plate and the transition between the two modes of vibration, at about the plate thickness, is abrupt. Using a laser excitation on the edge, the amplitude profile of the normal displacement at the edge resonance frequency was determined.

Adaptive projection method applied to three-dimensional ultrasonic focusing and steering through the ribs.

An adaptive projection method for ultrasonic focusing through the rib cage, with minimal energy deposition on the ribs, was evaluated experimentally in 3D geometry. Adaptive projection is based on decomposition of the time-reversal operator (DORT method) and projection on the "noise" subspace. It is shown that 3D implementation of this method is straightforward, and not more time-consuming than 2D. Comparisons are made between adaptive projection, spherical focusing, and a previously proposed time-reversal focusing method, by measuring pressure fields in the focal plane and rib region using the three methods. The ratio of the specific absorption rate at the focus over the one at the ribs was found to be increased by a factor of up to eight, versus spherical emission. Beam steering out of geometric focus was also investigated. For all configurations projecting steered emissions were found to deposit less energy on the ribs than steering time-reversed emissions: thus the non-invasive method presented here is more efficient than state-of-the-art invasive techniques. In fact, this method could be used for real-time treatment, because a single acquisition of back-scattered echoes from the ribs is enough to treat a large volume around the focus, thanks to real time projection of the steered beams.

[Surgical planes of the head and neck]. / Planos quirúrgicos en cabeza y cuello.

The surgical plane is a plane of dissection that can be used to excise a tumor while preserving most of the neurovascular structures. The majority of skin tumors are situated on the head and neck, and dermatologic surgeons should therefore have detailed knowledge of the surgical anatomy of this region. Fear of damaging important structures may result in insufficient efficacy of the surgical treatment, with consequent risk of persistence or recurrence of the tumor. Knowledge of the superficial musculoaponeurotic system and its relationship to key neurovascular structures enables the operation to be planned and will help us to locate the appropriate plane and minimize postoperative complications. The objective of this article is to review the key anatomical features defining suitable planes of dissection in the head and neck, the use of which will ensure survival of flaps and grafts.

Ultrasonic focusing through the ribs using the DORT method.

Thermal ablation induced by high intensity focused ultrasound has produced promising clinical results to treat hepatocarcinoma and other liver tumors. However skin burns have been reported due to the high absorption of ultrasonic energy by the ribs. This study proposes a method to produce an acoustic field focusing on a chosen target while sparing the ribs using the decomposition of the time-reversal operator (DORT method). The idea is to apply an excitation weight vector to the transducers array which is orthogonal to the subspace of emissions focusing on the ribs. A linear array of transducers has been used to measure the set of singular vectors associated with a chest phantom, made of three human ribs immersed in water, and to produce the desired acoustic fields. The resulting propagating fields have been measured both in the focal plane and in the plane of the ribs using a needle hydrophone. The ratio of the energies absorbed at the focal point and on the ribs has been enhanced up to 100-fold, as demonstrated by the measured specific absorption rates.

Familial Alzheimer's disease-linked presenilin 1 variants elevate Abeta1-42/1-40 ratio in vitro and in vivo.

Mutations in the presenilin 1 (PS1) and presenilin 2 genes cosegregate with the majority of early-onset familial Alzheimer's disease (FAD) pedigrees. We now document that the Abeta1-42(43)/Abeta1-40 ratio in the conditioned media of independent N2a cell lines expressing three FAD-linked PS1 variants is uniformly elevated relative to cells expressing similar levels of wild-type PS1. Similarly, the Abeta1-42(43)/Abeta1-40 ratio is elevated in the brains of young transgenic animals coexpressing a chimeric amyloid precursor protein (APP) and an FAD-linked PS1 variant compared with brains of transgenic mice expressing APP alone or transgenic mice coexpressing wild-type human PS1 and APP. These studies provide compelling support for the view that one mechanism by which these mutant PS1 cause AD is by increasing the extracellular concentration of Abeta peptides terminating at 42(43), species that foster Abeta deposition.

Vimentin isoform expression in the human retina characterized with the monoclonal antibody 3CB2.

The antigen recognized by the monoclonal antibody 3CB2 (3CB2-Ag and 3CB2 mAb) is expressed by radial glia and astrocytes in the developing and adult vertebrate central nervous system (CNS) of vertebrates as well as in neural stem cells. Here we identified the 3CB2-Ag as vimentin by proteomic analysis of human glial cell line U-87 extracts (derived from a malignant astrocytoma). Indeed, the 3CB2 mAb recognized three vimentin isoforms in glial cell lines. In the human retina, 3CB2-Ag was expressed in Müller cells, astrocytes, some blood vessels, and cells in the horizontal cell layer, as determined by immunoprecipitation and immunofluorescence. Three populations of astrocytes were distinguishable by double-labeling immunohistochemistry: vimentin+/GFAP+, vimentin-/GFAP+, and vimentin+/GFAP-. Hence, we conclude that 1) the 3CB2-Ag is vimentin; 2) vimentin isoforms are differentially expressed in normal and transformed astrocytes; 3) human retinal astrocytes display molecular heterogeneity; and 4) the 3CB2 mAb is a valuable tool to study vimentin expression and its function in the human retina.

Thymidine-phosphorothioate oligonucleotides induce activation and apoptosis of CLL cells independently of CpG motifs or BCL-2 gene interference.

We compared antisense phosphorothioate oligonucleotides (PS-ODN) that target BCL-2 such as Genasense (G3139-PS), with other PS-ODN or phosphodiester-ODN (PO-ODN) in their relative capacity to induce apoptosis of chronic lymphocytic leukemia (CLL) B cells in vitro. Surprisingly, we found that thymidine-containing PS-ODN, but not PO-ODN, induced activation and apoptosis of CLL cells independent of BCL-2 antisense sequence or CpG motifs. All tested thimidine-containing PS-ODN, irrespective of their primary sequences, reduced the expression of Bcl-2 protein and increased the levels of the proapoptotic molecules p53, Bid, Bax in CLL cells. Apoptosis induced by thymidine-containing PS-ODN was preceded by cellular activation, could be blocked by the tyrosine-kinase inhibitor imatinib mesylate (Gleevec), and was dependent on ABL kinase. We conclude that thymidine-containing PS-ODN can activate CLL cells and induce apoptosis via a mechanism that is independent of BCL-2 gene interference or CpG motifs.

Daratumumab, Elotuzumab, and the Development of Therapeutic Monoclonal Antibodies in Multiple Myeloma.

There has been substantial progress in clinical outcomes for patients with multiple myeloma (MM). This encouraging trend derives in large part from the increasing number of effective therapeutic options and the ability because of this to achieve higher quality responses to treatment. The approval of both daratumumab and of elotuzumab in combination with lenalidomide and dexamethasone, in late 2015, was a notable achievement in the field, as daratumumab and elotuzumab represent the first monoclonal antibodies available for use in MM. Given their unique mechanisms of action and favorable side effect profiles, daratumumab and elotuzumab have considerable potential as therapeutic partners with agents in other drug classes and in different clinical settings ranging from newly diagnosed to relapsed disease. This review discusses the development of daratumumab and elotuzumab as well as other monoclonal antibodies currently being evaluated for use in MM.

Neonatal Treatment with a Pegylated Leptin Antagonist Induces Sexually Dimorphic Effects on Neurones and Glial Cells, and on Markers of Synaptic Plasticity in the Developing Rat Hippocampal Formation.

The present study aimed to better understand the role of the neonatal leptin surge, which peaks on postnatal day (PND)9-10, on the development of the hippocampal formation. Accordingly, male and female rats were administered with a pegylated leptin antagonist on PND9 and the expression of neurones, glial cells and diverse markers of synaptic plasticity was then analysed by immunohistochemistry in the hippocampal formation. Antagonism of the actions of leptin at this specific postnatal stage altered the number of glial fibrillary acidic protein positive cells, and also affected type 1 cannabinoid receptors, synaptophysin and brain-derived neurotrophic factor (BDNF), with the latter effect being sexually dimorphic. The results indicate that the physiological leptin surge occurring around PND 9-10 is critical for hippocampal formation development and that the dynamics of leptin activity might be different in males and females. The data obtained also suggest that some but not all the previously reported effects of maternal deprivation on hippocampal formation development (which markedly reduces leptin levels at PND 9-10) might be mediated by leptin deficiency in these animals.

Accumulation of beta-amyloid fibrils in pancreas of transgenic mice.

Some forms of familial Alzheimer's disease are caused by mutations in the amyloid beta protein precursor (beta APP), and there is excellent evidence that these mutations foster amyloid deposition by increasing secretion of total amyloid beta protein (A beta) or the highly amyloidogenic A beta 1-42 form. These observations provide a powerful rationale for developing an animal model of AD by generating transgenic mice in which cerebral amyloid deposition is induced by A beta overproduction. To produce substantial A beta in vivo, we generated mice expressing the transgene of signal peptide and 99 residues of carboxyl-terminal fragment (CTF) of beta APP under control of the cytomegalovirus enhancer/chicken beta-actin promoter. The transgenic mRNA was detected in many tissues of these mice, but the levels of transgenic mRNA, CTF, and A beta did not correlate well indicating that tissue-specific posttranslational processing may play an important role in determining the amount of A beta that accumulates in various tissues. A beta was detected biochemically in brain, kidney, and pancreas with the largest amount present in pancreas. In transgenic plasma, there was a marked accumulation of human A beta 1-40 and A beta 1-42(43) to levels over 30-times those observed in normal human plasma. Thus, the transgenic mice produce and secrete considerable A beta. Despite this increase in A beta secretion and the elevated A beta in brain, immunohistochemistry revealed no consistent cerebral A beta deposition. In pancreas, however, intracellular A beta deposits were detected immunohistochemically in acinar cells and interstitial macrophages, some of which showed severe degeneration. In addition, examination of these cells by immunoelectron microscopy revealed many putative amyloid fibrils (7-12 nm) that were stained by anti-A beta antibodies. Overall, our findings indicate that tissue-specific posttranslational processing may play a pivotal role in A beta production and amyloid fibril formation in vivo. By carefully analyzing the changes that occur in the transgenic mice described here as compared to the transgenic line that has recently been shown to form extracellular amyloid plaques in brain, it may be possible to gain considerable insight into the factors that determine the location and amount of A beta that accumulates as amyloid.

A Shigella flexneri invasion plasmid gene, ipgH, with homology to IS629 and sequences encoding bacterial sugar phosphate transport proteins.

Sequences representing the 2684 bp flanking the ipaH4.5 gene on the invasion plasmid of Shigella flexneri 5 indicate an unusual fusion gene, designated ipgH, in which the first 27 amino acids (aa) are identical to ORF2 of IS629. The aa sequence encoded by the remainder of ipgH bears significant homology to Escherichia coli and to Salmonella typhimurium GlpT and UhpT proteins and to the S. typhimurium PgtP protein, which are involved in the uptake of high-energy sugar phosphates from an external source.