Alternatives for the treatment of schistosomiasis: physico-chemical characterization of an inclusion complex between praziquantel and hydroxypropyl-β-cyclodextrin

O praziquantel (PZQ) é o fármaco de escolha no tratamento da esquistossomose. Porém, ele apresenta baixa solubilidade aquosa, o que pode limitar a sua biodisponibilidade no organismo. Para contornar estas características foi feita a inclusão da molécula do PZQ em hidroxipropil-beta-ciclodextrina (HP-β-CD). Desta forma, o objetivo deste trabalho foi preparar e caracterizar o complexo de inclusão PZQ/HP-β-CD. Estudos morfológicos, espectroscópicos e de calorimetria diferencial de varredura, demonstraram os primeiros indícios da interação hóspede/hospedeiro. Analisando a cinética de incorporação da molécula de PZQ na cavidade da HP-β-CD, pode-se determinar a constante cinética, além do tempo para equilíbrio do sistema. Utilizando-se isoterma de solubilidade foi possível observar que a interação com HP-β-CD aumentou a solubilidade aquosa do PZQ em 2,4 vezes. Ensaios de citotoxicidade in vitro, utilizando fibroblastos, demonstraram não haver indícios de toxicidade para estas células, nas concentrações testadas. Os resultados indicam que há um potencial favorável da aplicação deste fármaco na forma complexada em HP-β-CD.Colegio de Farmacéuticos de la Provincia de Buenos Aire

A Multi-Center Study to Evaluate the Performance of Phage Amplified Biologically Assay for Detecting TB in Sputum in the Pulmonary TB Patients

Objective: To evaluate the performance of phage amplified biologically assay (PhaB) for detecting tuberculosis (TB) in sputum in the pulmonary tuberculosis (PTB) patients. Methods: Shanghai Tuberculosis Key Laboratory of Shanghai Pulmonary Hospital participated in the project in collaboration with the laboratories of six hospitals and a total of 1660 eligible participants (1351 PTB patients and 309 non-TB patients) were included in the study. The sputum samples from the participants were detected by smear microscopy, PhaB, and Löwenstein-Jensen (L-J) culture method, respectively. Results: The overall sensitivity of PhaB were higher than that of L-J culture and smear microscopy (p,0.05). The sensitivity of PhaB for detecting smear-negative specimens was obviously higher than that of L-J culture (p,0.05). Compared with L-J culture, the overall sensitivity, specificity, PPV, NPV, ACC and Kappa value of PhaB were 98.4 (95 % Cl: 96.9–99.3), 71.6 (95% Cl: 68.4–74.6), 67.7, 98.7, 81.7 % and 0.643, respectively. The detection median time of PhaB only needed 48 hours, which was significantly less than that (31 days) of L-J culture method. Conclusion: PhaB method is a rapid and sensitive method for detecting TB in sputum in PTB patients; especially for th

Non-Agonistic Bivalent Antibodies That Promote c-MET Degradation and Inhibit Tumor Growth and Others Specific for Tumor Related c-MET

The c-MET receptor has a function in many human cancers and is a proven therapeutic target. Generating antagonistic or therapeutic monoclonal antibodies (mAbs) targeting c-MET has been difficult because bivalent, intact anti-Met antibodies frequently display agonistic activity, necessitating the use of monovalent antibody fragments for therapy. By using a novel strategy that included immunizing with cells expressing c-MET, we obtained a range of mAbs. These c-MET mAbs were tested for binding specificity and anti-tumor activity using a range of cell-based techniques and in silico modeling. The LMH 80 antibody bound an epitope, contained in the small cysteine-rich domain of c-MET (amino acids 519–561), that was preferentially exposed on the c-MET precursor. Since the c-MET precursor is only expressed on the surface of cancer cells and not normal cells, this antibody is potentially tumor specific. An interesting subset of our antibodies displayed profound activities on c-MET internalization and degradation. LMH 87, an antibody binding the loop connecting strands 3d and 4a of the 7-bladed β-propeller domain of c-MET, displayed no intrinsic agonistic activity but promoted receptor internalization and degradation. LMH 87 inhibited HGF/SF-induced migration of SK-OV-3 ovarian carcinoma cells, the proliferation of A549 lung cancer cells and the growth of human U87MG glioma cells in a mouse xenograft model. These results indicate that c-MET antibodies targeting epitopes controlling receptor internalization and degradation provide new ways of controlling c-MET expression and activity and may enable the therapeutic targeting of c-MET by intact, bivalent antibodies

Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine

[This corrects the article DOI: 10.1186/s13054-016-1208-6.]

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Heranças familiares: entre os genes e os afetos

Sabe-se que o câncer de mama é uma patologia que afeta um número considerável de mulheres e levanta diversos questionamentos entre os profissionais da saúde. A história familiar é considerada um fator de risco e os profissionais das diversas áreas da saúde apontam-na como fator decisivo na determinação de aspectos relativos ao processo de adoecimento. Entretanto, a história familiar é abordada de maneiras distintas pelos diferentes profissionais, de acordo com o enfoque tomado. O presente artigo propõe uma leitura global da história familiar considerando as diversas "heranças" que atravessam e constituem o sujeito. A partir da análise de instrumentos como o heredograma e o genograma, observa-se que, enquanto o saber médico se ocupa de uma história familiar que está previamente determinada por fatores genéticos e, portanto, pouco acessível à intervenções preventivas, o saber psicológico busca o que há de particular na história familiar do sujeito e na maneira como este se insere na trama das relações que compõem essa história. Desse modo, abre-se a possibilidade de re-significar essa história e de encontrar uma outra via que não a do adoecer. Propicia-se, a partir daí, um espaço de discussão onde saberes e práticas interdisciplinares possam se complementar na perspectiva de uma integralidade na prevenção e promoção da saúde.It is known that breast cancer is a pathology that affects a considerable number of women and gives rise to many interrogations amongst health professionals . Family history is considered a risk factor and professionals from all health branches point it as a decisive factor in determining multiple aspects related to sickness processes. However, family history is approached in different ways by different professionals, according to the focus that is given. The present article proposes a global view of the family history by taking into account the multiple "heritages" that cross and constitute the subject. From the analysis of instruments as the drawing of human pedigrees and genogram it is observed that, whereas medical cknowledge is engaged in a family history that is previously determined by genetic factors, and consequently, very little accessible to preventive interventions, psychological cknowledge seeks the particularities of subject's family history and the manners through which the subject inserts himself on the relations that compose his history. Doing so, it is possible to give new significations to family history and to open another way that is not to become ill. It is also provided, from that point, a space of discussion where interdisciplinary cknowledges and practices may complement each other in a perspective of integrality in the prevention and the promotion of human health

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency–Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research