Successful treatment of Verona integron-encoded metallo-ß-lactamase-producing Klebsiella pneumoniae infection using the combination of ceftazidime/avibactam and aztreonam.

The case of a female who had an accident that caused an open fracture is reported. During hospitalisation, Verona integron-encoded metallo-ß-lactamase (VIM)-producing Klebsiella pneumoniae was isolated. Antimicrobial susceptibility testing revealed resistance to ß-lactam antibiotics, quinolones, trimethoprim/sulfamethoxazole, and susceptibility to tigecycline, colistin, fosfomycin and aminoglycosides. Synergistic activity of ceftazidime-avibactam and aztreonam was proved in vitro and a combined therapy with tigecycline was started. Combination with aminoglycosides was ruled out as it was not described in the literature and also in order to avoid side effects. Colistin was rejected because of its nephrotoxicity profile. The antibiotic treatment was assessed by a multidisciplinary team with a pharmacist who closely monitored adverse effects and interactions with other drugs. The total duration of this combination was 25 days, without any adverse events reported. Fourteen weeks after the accident the patient was discharged. After 2 months of follow-up neither relapses nor reinfections have been reported.

Bartonella henselae encephalopathy in a paediatric patient: A case report and treatment review.

WHAT IS KNOWN AND OBJECTIVES: Bartonella henselae is the etiologic agent of "cat scratch disease (CSD)". We describe a case of atypical CSD in a paediatric patient and include a review of the antibiotic treatment for this disease. CASE DESCRIPTION: A 2-year-old child, with convulsive status and loss of consciousness, was admitted to hospital. Several antiepileptics and antibiotics were prescribed due to suspected central nervous system infection. When serology revealed Bartonella henselae antibodies, targeted antibiotic therapy was initiated and symptoms improved. However, seizures reappeared days after finishing the treatment so antiepileptics and antibiotics were reintroduced. WHAT IS NEW AND CONCLUSION: A wide variety of antibiotic regimens have been used for the treatment of atypical CSD in paediatric patients. This report includes the case of a paediatric patient diagnosed with atypical CSD who presented neurological manifestations, and for which a regimen consisting of azithromycin and rifampin was employed to achieve recovery.

Dalbavancina combinada con linezolid en infección protésica de cadera / Dalbavancin combined with linezolid in prosthetic-hip infection

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Beyond the CNS: The many peripheral roles of APOE.

Apolipoprotein E (APOE) is a multifunctional protein synthesized and secreted by multiple mammalian tissues. Although hepatocytes contribute about 75% of the peripheral pool, APOE can also be expressed in adipose tissue, the kidney, and the adrenal glands, among other tissues. High levels of APOE production also occur in the brain, where it is primarily synthesized by glia, and peripheral and brain APOE pools are thought to be distinct. In humans, APOE is polymorphic, with three major alleles (ε2, ε3, and ε4). These allelic forms dramatically alter APOE structure and function. Historically, the vast majority of research on APOE has centered on the important role it plays in modulating risk for cardiovascular disease and Alzheimer's disease. However, the established effects of this pleiotropic protein extend well beyond these two critical health challenges, with demonstrated roles across a wide spectrum of biological conditions, including adipose tissue function and obesity, metabolic syndrome and diabetes, fertility and longevity, and immune function. While the spectrum of biological systems in which APOE plays a role seems implausibly wide at first glance, there are some potential unifying mechanisms that could tie these seemingly disparate disorders together. In the current review, we aim to concisely summarize a wide breadth of APOE-associated pathologies and to analyze the influence of APOE in the development of several distinct disorders in order to provide insight into potential shared mechanisms implied in these various pathophysiological processes.

Plausibility of a Neural Network Classifier-Based Neuroprosthesis for Depression Detection via Laughter Records.

The present work explores the diagnostic performance for depression of neural network classifiers analyzing the sound structures of laughter as registered from clinical patients and healthy controls. The main methodological novelty of this work is that simple sound variables of laughter are used as inputs, instead of electrophysiological signals or local field potentials (LFPs) or spoken language utterances, which are the usual protocols up-to-date. In the present study, involving 934 laughs from 30 patients and 20 controls, four different neural networks models were tested for sensitivity analysis, and were additionally trained for depression detection. Some elementary sound variables were extracted from the records: timing, fundamental frequency mean, first three formants, average power, and the Shannon-Wiener entropy. In the results obtained, two of the neural networks show a diagnostic discrimination capability of 93.02 and 91.15% respectively, while the third and fourth ones have an 87.96 and 82.40% percentage of success. Remarkably, entropy turns out to be a fundamental variable to distinguish between patients and controls, and this is a significant factor which becomes essential to understand the deep neurocognitive relationships between laughter and depression. In biomedical terms, our neural network classifier-based neuroprosthesis opens up the possibility of applying the same methodology to other mental-health and neuropsychiatric pathologies. Indeed, exploring the application of laughter in the early detection and prognosis of Alzheimer and Parkinson would represent an enticing possibility, both from the biomedical and the computational points of view.

Fundamental, Quantitative Traits of the "Sociotype".

In whatever domain of life, from cells to organisms to societies, communicative exchanges underlie the formation and maintenance, and decay, of the emerging collective structures. It can be clearly seen in the human social world. The different classes of social bonds in a complex society revolve around, and are intimately related with, the communicative relationships that every individual entertains-essentially via face-to-face conversation. In the present work we have investigated the fundamental metrics of both social bonds and communicative exchanges along the development of the "sociotype" construct. It is a new approach developed by the authors within the genotype-phenotype-sociotype conceptual triad. The sociotype means the relative constancy, or better the similar fabric, of the social world in which each individual life is developed. In order to ascertain the metrics of the fundamental quantitative traits inherent in the sociotype, a fieldwork involving a total of 1475 individuals (68.59% female, and 49.79 mean age, SD = 21.47) was carried out. The four relational realms of family, friends, work/study, and acquaintances were investigated. The overall results about conversation time (an average of 220 min/day), and about the number of social bonds (an average of 98), differ from previous assumptions, such as Dunbar's number or Killworth's number. Other results about gender, age, and use of social media and Internet contribute to highlight significant differences among the different social segments, and particularly the diminished "sociotype" of the elderly. Finally, it is curious that a non-Gaussian distribution has been obtained for the specific population allotment of these metrics, and intriguingly the Planckian distribution equation (PDE) appears to be a most cogent fit.

The Dietary Antioxidant Piceatannol Inhibits Adipogenesis of Human Adipose Mesenchymal Stem Cells and Limits Glucose Transport and Lipogenic Activities in Adipocytes.

Phenolic compounds are among the most investigated herbal remedies, as is especially the case for resveratrol. Many reports have shown its anti-aging properties and the ability to reduce obesity and diabetes induced by high-fat diet in mice. However, such beneficial effects hardly translate from animal models to humans. The scientific community has therefore tested whether other plant phenolic compounds may surpass the effects of resveratrol. In this regard, it has been reported that piceatannol reproduces in rodents the anti-obesity actions of its parent polyphenol. However, the capacity of piceatannol to inhibit adipocyte differentiation in humans has not been characterized so far. Here, we investigated whether piceatannol was antiadipogenic and antilipogenic in human preadipocytes. Human mesenchymal stem cells (hMSC), isolated from adipose tissues of lean and obese individuals, were differentiated into mature adipocytes with or without piceatannol, and their functions were explored. Fifty µM of piceatannol deeply limited synthesis/accumulation of lipids in both murine and hMSC-derived adipocytes. Interestingly, this phenomenon occurred irrespective of being added at the earlier or later stages of adipocyte differentiation. Moreover, piceatannol lowered glucose transport into adipocytes and decreased the expression of key elements of the lipogenic pathway (PPARγ, FAS, and GLUT4). Thus, the confirmation of the antiadipogenic properties of piceatanol in vitro warrants the realization of clinical studies for the application of this compound in the treatment of the metabolic complications associated with obesity.

How prokaryotes 'encode' their environment: Systemic tools for organizing the information flow.

An important issue related to code biology concerns the cell's informational relationships with the environment. As an open self-producing system, a great variety of inputs and outputs are necessary for the living cell, not only consisting of matter and energy but also involving information flows. The analysis here of the simplest cells will involve two basic aspects. On the one side, the molecular apparatuses of the prokaryotic signaling system, with all its variety of environmental signals and component pathways (which have been called 1-2-3 Component Systems), including the role of a few second messengers which have been pointed out in bacteria too. And in the other side, the gene transcription system as depending not only on signaling inputs but also on a diversity of factors. Amidst the continuum of energy, matter, and information flows, there seems to be evidence for signaling codes, mostly established around the arrangement of life-cycle stages, in large metabolic changes, or in the relationships with conspecifics (quorum sensing) and within microbial ecosystems. Additionally, and considering the complexity growth of signaling systems from prokaryotes to eukaryotes, four avenues or "roots" for the advancement of such complexity would come out. A comparative will be established in between the signaling strategies and organization of both kinds of cellular systems. Finally, a new characterization of "informational architectures" will be proposed in order to explain the coding spectrum of both prokaryotic and eukaryotic signaling systems. Among other evolutionary aspects, cellular strategies for the construction of novel functional codes via the intermixing of informational architectures could be related to the persistence of retro-elements with obvious viral ancestry.

The "sociotype" construct: Gauging the structure and dynamics of human sociality.

Exploring the pertinence of a "sociotype" construct, established along the conceptual chain genotype-phenotype-sociotype, is the essential purpose of the present paper. Further, by following the sociotype's conceptual guidelines, a new psychometric indicator has been developed in order to gauge the level of social interaction around each individual-the sociotype questionnaire (SOCQ). A first version of this questionnaire has been elaborated by gathering data about the different classes of social bonds (family, friends, acquaintances, and work/study colleagues) in general population and about the dynamic update of these bonds via face-to-face conversation and other modes of interaction. A specific fieldwork was undertaken, involving 1,075 participants, all of them Spanish adults (with diverse social and regional backgrounds). The data obtained were analyzed by means of the correlational method with an analytical cross-sectional design: the number of factors and the consistency and reliability of the resulting scales were evaluated and correlated. The new sociotype indicator resulting from that fieldwork, in spite of its limitations, seems to be valid and reliable, as well as closely associated with widely used metrics of loneliness and psychological distress. It is interesting that the construct noticeably varies throughout the life course and circumstances of individuals, based on their gender and age, and adjusting to the different situations of social networking. This is the first study, to the best of our knowledge, which has tried to reach both a theoretical and an operational formulation of the sociotype construct, by establishing an ad hoc psychometric questionnaire. We think that the information provided by this operational definition opens a new direction of work that could be useful to guide the development and evaluation of programs aimed at improving and strengthening social networking in people at risk, especially for the elderly.

Use of negative pressure wound therapy after infection and flap dehiscence in radical vulvectomy: A case report.

INTRODUCTION: Vulvar cancer has a lower incidence in high income countries, but is rising, in part, due to the high life expectancy in these societies. Radical vulvectomy is still the standard treatment in initial stages. Wound dehiscence contitututes one of the most common postoperative complications. PRESENTATION OF CASE: A 76year old patient with a squamous cell carcinoma of the vulva, FIGO staged, IIIb is presented. Radical vulvectomy and bilateral inguinal lymph node dissection with lotus petal flaps reconstruction are performed as the first treatment. Wound infection and dehiscence of lotus petal flaps was seen postoperatively. Initial management consisted in antibiotics administration and removing necrotic tissue from surgical wound. After this initial treatment, negative wound pressure therapy was applied for 37days with good results. DISCUSSION: Wound dehiscence in radical vulvectomy remains the most frequent complication in the treatment of vulvar cancer. The treatment of this complications is still challenging for most gynecologic oncologist surgeons. CONCLUSION: The utilization of the negative wound pressure therapy could contribute to reduce hospitalization and the direct and indirect costs of these complications.

Treatment and follow-up in an asymptomatic malignant struma ovarii: A case report.

INTRODUCTION: Struma ovarii is a rare ovarian tumor, representing 0.5-1% of all ovarian tumors and 2-5% of ovarian teratomas. It is defined as an ovarian teratoma composed mostly of thyroid tissue. The symptoms are nonspecific, and the imaging studies can help in characterize the mass; however, the definitive diagnosis is usually given by the Pathologist. Classically, the treatment is the surgical resection of the ovarian mass, however there is no consensus regarding the follow-up. PRESENTATION OF CASE: An asymptomatic malignant struma ovarii in a 43 year-old patient is presented. The diagnosis was postoperatively following a laparoscopic adnexectomy due to an apparently benign ovarian teratoma. The histopathology results revealed a mature ovarian cystic teratoma with papillary carcinoma with immunohistochemical characteristics suggesting a thyroid origin. Seeing that there was no thyroid affectation or metastatic disease, we decided a conservative management. A yearly follow-up with CT scan and tumor markers was performed. The endocrinologist also performed annual controls with thyroid ultrasound and serum tests. The patient has remained asymptomatic during these last four years. DISCUSSION: There is little evidence in literature on the conservative management in cases with evidence of malignancy. If fertility preservation is desired, an unilateral oophorectomy could be performed, along with levels of serum thyroglobulin as a marker of relapse. Other authors claim for aggressive ovarian cancer surgery followed by a total thyroidectomy. There is still no established management for struma ovarii patients and the choice for a conservative or radical approach depends only on the professional decision.

How the living is in the world: An inquiry into the informational choreographies of life.

Understanding the nature of life has always been a fundamental objective of human knowledge. It is no wonder that biology, as the science of life, together with physics, has traditionally been the discipline that has generated the deepest philosophical and social repercussions. In our time, the major achievements in bioinformatics, systems biology, and "omic" fields (genomics, proteomics, metabolomics, etc.) have not only spurred a new biotechnological and biomedical 'postindustrial revolution', but they have also disclosed an intriguing molecular panorama of biological organization that invites us to reinterpret central themes of philosophy in the light of the new knowledge. Essential tenets of phenomenology may take an intriguing new turn when contemplated from these new biological perspectives: Does the living cell instantiate a unique biomolecular way of being in the world? How is life self-produced in continuous communication with the surrounding world? How can the incessant flows of mass, energy and information inherent of embodiment be coherently harnessed across billions of cellular individuals? In this paper, based on the latest developments in cellular signaling, we will discuss the dynamic intertwining between self-production and communication that characterizes life at the prokaryotic, eukaryotic, organismic, and social levels of organization. An in-depth analysis of the particular transcriptional responses of a bacterium (Escherichia coli K-12 strain), taking as a model system, will follow. It is the creation, transmission and reception of signals which, in all instances, provides guidance and orientation to the inner self-production activities of the living agent and connects it with the world. Transitions to new levels of organization are marked by the emergence of new forms of communication, embedded in the correspondingly augmented life-cycles of the more complex entities. As will be argued here, the ascending complexity of life is always information-based and recapitulates level after level, a successful "informational formula" for being in the world. The phenomenological basis for the naturalization of cognition has moved from the biological to a new scientific arena: informational. The philosophical notion of being-in-the-world (Dasein; Heidegger) is shown to be completely compatible with the latest advances in biology and information science.

Study of neuron survival on polypyrrole-embedded single-walled carbon nanotube substrates for long-term growth conditions.

Cultures of primary embryonic rat brain hippocampus neurons with supporting glia cells were carried out on different substrates containing polypyrrole (PPy) and/or single-walled carbon nanotubes (SWCNTs). Neuron adhesion, neurites and dendrites branching elongation, and development of neuron networks on substrates were followed by phase-contrast optical microscopy and quantified to state cell survival and proliferation. Suspensions of as-grown and purified SWCNTs were sprayed on a glass coverslips and PPy/SWCNTs were deposited by potentiodynamic electrochemical deposition. Cell neurotoxicity revealed by neuron death was very high for purified SWCNTs substrates in good agreement with [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] (MTT) test showing lower viability on SWCNTs containing substrates compared with PPy-substrates and control samples probably due to the metal content and the carboxylic groups introduced during the purification. It is interesting to highlight that neurons grown on PPy-substrates adhere developing neurites and branching dendrites earlier even than on control cultures. On subsequent days the neurons are able to adapt to nanotube substrates developing neuron networks for 14-day cultures with similar patterns of complexity for control, PPy and PPy/SWCNT substrates. PPy/SWCNT substrates show a lower impedance value at frequencies under 1 Hz. We have come to the conclusion that glia cells and PPy added to the culture medium and substrates respectively, improve in some degree nanotube biocompatibility, cell adhesion and hence cell viability.

On eukaryotic intelligence: signaling system's guidance in the evolution of multicellular organization.

Communication with the environment is an essential characteristic of the living cell, even more when considering the origins and evolution of multicellularity. A number of changes and tinkering inventions were necessary in the evolutionary transition between prokaryotic and eukaryotic cells, which finally made possible the appearance of genuine multicellular organisms. In the study of this process, however, the transformations experimented by signaling systems themselves have been rarely object of analysis, obscured by other more conspicuous biological traits: incorporation of mitochondria, segregated nucleus, introns/exons, flagellum, membrane systems, etc. Herein a discussion of the main avenues of change from prokaryotic to eukaryotic signaling systems and a review of the signaling resources and strategies underlying multicellularity will be attempted. In the expansion of prokaryotic signaling systems, four main systemic resources were incorporated: molecular tools for detection of solutes, molecular tools for detection of solvent (Donnan effect), the apparatuses of cell-cycle control, and the combined system endocytosis/cytoskeleton. The multiple kinds of enlarged, mixed pathways that emerged made possible the eukaryotic revolution in morphological and physiological complexity. The massive incorporation of processing resources of electro-molecular nature, derived from the osmotic tools counteracting the Donnan effect, made also possible the organization of a computational tissue with huge information processing capabilities: the nervous system. In the central nervous systems of vertebrates, and particularly in humans, neurons have achieved both the highest level of molecular-signaling complexity and the highest degree of information-processing adaptability. Theoretically, it can be argued that there has been an accelerated pace of evolutionary change in eukaryotic signaling systems, beyond the other general novelties introduced by eukaryotic cells in their handling of DNA processes. Under signaling system's guidance, the whole processes of transcription, alternative splicing, mobile elements, and other elements of domain recombination have become closely intertwined and have propelled the differentiation capabilities of multicellular tissues and morphologies. An amazing variety of signaling and self-construction strategies have emerged out from the basic eukaryotic design of multicellular complexity, in millions and millions of new species evolved. This design can also be seen abstractly as a new kind of quasi-universal problem-solving 'engine' implemented at the biomolecular scale-providing the fundamentals of eukaryotic 'intelligence'. Analyzing in depth the problem-solving intelligence of eukaryotic cells would help to establish an integrative panorama of their information processing organization, and of their capability to handle the morphological and physiological complexity associated. Whether an informational updating of the venerable "cell theory" is feasible or not, becomes, at the time being - right in the middle of the massive data deluge/revolution from omic disciplines - a matter to careful consider.

Using living cells to transport therapeutic genes for cancer treatment.

One of the key problems in cancer gene therapy is the inefficient delivery of therapeutic transgenes to tumour sites, after the systemic injection of the viral vector. Hence, new vector discovery is extremely important for the improvement of gene therapy results. Previously, mammalian cells were proposed as new vector systems; however with recent advances in stem cell research this modality makes them more suitable candidates. Tumours are composed of both malignant and benign cells. As "benign" cell types are able to form blood vessels, and stroma, it has been hypothesised that exogenously administrated cells of a different kind would preferentially engraft at the stromal tumour site and could deliver cancer gene therapy vectors to tumours.

On prokaryotic intelligence: strategies for sensing the environment.

The adaptive relationship with the environment is a sine qua non condition for any intelligent system. Discussions on the nature of cellular intelligence, however, have not systematically pursued yet the question of whether there is a fundamental way of sensing the environment, which may characterize prokaryotic cells, or not. The molecular systems found in bacterial signaling are extremely diverse, ranging from very simple transcription regulators (single proteins comprising just two domains) to the multi-component, multi-pathway signaling cascades that regulate crucial stages of the cell cycle, such as sporulation, biofilm formation, dormancy, pathogenesis or flagellar biosynthesis. The combined complexity of the environment and of the cellular way of life is reflected as a whole in the aggregate of signaling elements: an interesting power-law relationship emerges in that regard. In a basic taxonomy of bacterial signaling systems, the first level of complexity corresponds to the simplest regulators, the "one-component systems" (OCSs), which are defined as proteins that contain known or predicted input and output domains but lack histidine kinase and receiver domains. They are evolutionary precursors of the "two-component systems" (TCSs), which include histidine protein-kinase receptors and an independent response regulator, and are considered as the central signaling paradigm within prokaryotic organisms. The addition of independent receptors begets further functional complexity: thus, "three-component systems" (ThCSs) should be applied to those two-component systems that incorporate an extra non-kinase receptor to activate the protein-kinase. Further, the combined information processing functions (cross-talk) and integrative dynamics that OCS, TCS and ThCS may achieve together in the prokaryotic cell have to be depicted, as well as the relationship of these informational functions with the life cycle organization and its checkpoints. Finally, the extent to which formal models would capture the ongoing relationship of the living cell with its medium has to be gauged, in the light of both the complexity of molecular recognition events and the impredicative nature of living systems.

Corcondancia electroencefálica: aplicación al diagnóstico en fibromialgia / No disponible

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