Ivermectin-Loaded Mesoporous Silica and Polymeric Nanocapsules: Impact on Drug Loading, In Vitro Solubility Enhancement, and Release Performance.

Ivermectin (IVM), a widely used drug for parasitic infections, faces formulation and application challenges due to its poor water solubility and limited bioavailability. Pondering the impact of IVM's high partition coefficient value (log P) on its drug release performance, it is relevant to explore whether IVM nanoencapsulation in organic or inorganic nanoparticles would afford comparable enhanced aqueous solubility. To date, the use of inorganic nanoparticles remains an unexplored approach for delivering IVM. Therefore, here we loaded IVM in mesoporous silica particles (IVM-MCM), as inorganic nanomaterial, and in well-known poly(ε-caprolactone) nanocapsules (IVM-NC). IVM-MCM had a well-organized hexagonal mesoporous structure, reduced surface area, and high drug loading of 10% w/w. IVM-NC had a nanometric mean size (196 nm), high encapsulation efficiency (100%), physicochemical stability as an aqueous dispersion, and drug loading of 0.1% w/w. Despite differing characteristics, both nanoencapsulated forms enhance IVM's aqueous intrinsic solubility compared to a crystalline IVM: after 72 h, IVM-MCM and IVM-NC achieve 72% and 78% releases through a dialysis bag, whereas crystalline IVM dispersion achieves only 40% drug diffusion. These results show distinct controlled release profiles, where IVM-NC provides a deeper sustained controlled release over the whole experiment compared to the inorganic nanomaterial (IVM-MCM). Discussing differences, including drug loading and release kinetics, is crucial for optimizing IVM's therapeutic performance. The study design, combined with administration route plans and safety considerations for humans and animals, may expedite the rational optimization of IVM nanoformulations for swift clinical translation.

Flow cytometry immunophenotyping of healthy platelets and hospitalized patients with suspected platelet dysfunction: Challenges for establishing a cutoff value.

INTRODUCTION AND OBJECTIVE: Flow Cytometry (FC) is one of the techniques, which allows the identification and characterization of platelets. The detection of absent or reduced expression of the glycoproteins is the main objective of this technique. Abnormalities of glycoproteins lead to hemorrhagic syndromes. Among the main diseases, the Bernard-Soulier syndrome (BSS) and Glanzmann thrombasthenia (GT) stand out. We aimed to show a FC-based platelet assessment test for diagnostic use, which measures the expression of markers in normal patients, and evaluate these markers in patients with platelet disorders. METHODS: We examined a control group of 41 healthy adults to establish reference values and assess the variability of the relative expression of platelet markers and subsequently compared these findings to those of 30 patients with suspected platelet dysfunctions. We determined the mean fluorescent intensity (MFI) of the expressed parameters by FC using CD41, CD42a, CD42b and CD61 and SSC/FSC platelet-gated cells. RESULTS: We determined our baseline panel of markers and compared them to suspected platelet dysfunctions. Patients with suspected BSS presented increased levels of the MFI for the GPIIIa (CD61) and GPIIb (CD41). They showed significantly reduced levels of the GPIb (CD42b) and GPIX (CD42a). Patients with suspected GT showed normal expression of the GPIX (CD42a), increased expression of the GPIb (CD42b) and reduced levels of the GPIIIa (CD61). In this case, with reduced levels of only one marker, the GPIIb (CD41), values showed normal expression. CONCLUSIONS: We describe the FC assay to support the diagnosis of different platelet disorders. Our study made it possible to implement a technique that brought benefits to care.

Environmental enrichment affects behavioral and pharmacological response to antidepressants in CF1 mice.

It has been described that environmental enrichment (EE) exerts beneficial effects on cognitive and emotional performances, dendritic branching, synaptic density, neurogenesis and modulation of neurotrophic systems and neurotransmitters in rodents. However, the influence of EE on pharmacological and behavioral responses in animal models of psychiatric disorders has not been fully established. In this context, the aim of this study was to evaluate the influence of exposure to EE on mice behavior in the open field test (OFT) and forced swimming tests (FST), as well as the response to antidepressant drugs (fluoxetine 30 mg/kg and bupropion 30 mg/kg, p.o.). CF1 mice were exposed to an enriched housing condition at different developmental stages: from mating to postnatal day (PND) 55 (lifelong enrichment), from mating to PND21 (perinatal enrichment) and from PND21 to PND55 (post-weaning enrichment). At PND58 the male offspring were evaluated in the OFT and FST. BDNF gene expression in the hippocampus was determined through qPCR. Mice exposed to perinatal enrichment remained longer in the peripheral zone of the OFT and performed fewer grooming than mice housed under standard condition, and these effects were independent of drug treatment. Post-weaning and lifelong enrichment increased grooming behavior. Bupropion reduced grooming in all groups except in perinatal enriched. In turn, fluoxetine decreased grooming only in post-weaning enriched group. None of the enriched housing conditions altered the immobility time in the FST, which indicates that EE had no antidepressant-like effect. However, all enriched housing conditions abolished the anti-immobility effect of bupropion. None of the EE protocols affected BDNF hippocampal expression. The main conclusion is that mice behavior in the OFT is sensitive to alterations in the housing environment and depends on the developmental stage of exposure. Bupropion and fluoxetine yielded divergent responses depending on the housing condition, which suggests that EE modulates monoaminergic neurotransmission pathways.

Betulinic Acid-Brosimine B Hybrid Compound Has a Synergistic Effect with Imatinib in Chronic Myeloid Leukemia Cell Line, Modulating Apoptosis and Autophagy.

Chronic myeloid leukemia (CML) is a myeloproliferative disease characterized by the formation of the BCR-ABL (breakpoint cluster region-Abelson) oncoprotein. As many patients display therapeutic resistance, the development of new drugs based on semisynthetic products represents a new potential therapeutic approach for treating the disease. In this study, we investigated the cytotoxic activity, possible mechanism of action of a hybrid compound of betulinic acid (BA) and brosimine B in CML cell lines that are sensitive (K-562) and resistant (K-562R) to imatinib, in addition to evaluating lower doses of imatinib in combination with the hybrid compound. The effects of the compound, and its combination with imatinib, on apoptosis, cell cycle, autophagy and oxidative stress were determined. The compound was cytotoxic in K-562 (23.57 ± 2.87 µM) and K-562R (25.80 ± 3.21 µM) cells, and a synergistic effect was observed when it was associated with imatinib. Apoptosis was mediated by the caspase 3 and 9 intrinsic pathway, and cell cycle evaluation showed arrest at G0/G1. In addition, the hybrid compound increased the production of reactive oxygen species and induced autophagy by increasing LC3II and Beclin-1 mRNA levels. Results suggest that this hybrid compound causes the death of both imatinib-sensitive and -resistant cell lines and may hold potential as a new anticancer treatment against CML.

Comparison of Nonsequencing Techniques for Identification of NPM1 Mutations and Associated Blast Morphology in Patients With Acute Myeloid Leukemia.

CONTEXT.­: Nucleophosmin 1 (NPM1) mutations affect 20% to 30% of all acute myeloid leukemia (AML) patients; several methods are employed to analyze NPM1 mutations, each of them with its advantages and limitations. OBJECTIVE.­: To compare 3 nonsequencing protocols capable of detecting the main NPM1 mutations and to evaluate nuclear morphometric analysis (NMA) as an alternative to cuplike blast detection. DESIGN.­: We selected multiparameter flow cytometry (MFC), amplification refractory mutation system-polymerase chain reaction (ARMS-PCR), and a quantitative PCR (qPCR) kit to identify NPM1 mutations in AML patients at diagnosis. We also evaluated the presence of cuplike blasts and assessed nuclear morphometry using NMA. RESULTS.­: MFC appears as a screening method for NPM1 mutations because of its lower specificity. ARMS-PCR demonstrated specificity similar to that of the qPCR kit, although it was more laborious. qPCR testing, conversely, is relatively fast and easy to standardize. Of these methods, qPCR was the only one capable of identifying the type of NPM1 mutation. With regard to morphology, NMA could be used as an alternative for the evaluation of cuplike blasts in AML smears. CONCLUSIONS.­: qPCR appears to be the best option to identify NPM1 mutations, with ARMS-PCR representing a cheaper alternative. MFC may be used as a screening method, in which results falling within and above the gray zone should be confirmed by molecular testing.

Kinetics and mineralization fraction of organic matter from sewage sludge mixed with soil under controlled laboratory conditions.

The objective of this work was to evaluate the kinetics and mineralization fraction of organic matter from sewage sludge mixed with the soil under controlled laboratory conditions. For this, organic material samples accumulated in layers 0-5 cm, 5-10 cm and 10-15 cm in relation to the surface of a vertical flow constructed wetland system (VF-CW) used for treatment of septic tank sludge, in addition to samples of dewatered sludge from a septic tank and a UASB reactor and non-dewatered sludge from an anaerobic digester were mixed with material collected from the surface layer of a Red Yellow Argisol at rates equivalent to the applications, via organic residues, of 300 and 600 kg ha-1 year-1 of total nitrogen. It was found that the two-phase kinetic equation fit better to the mineralization data of labile and recalcitrant organic carbon. For the lowest nitrogen application rate in the mixtures, the mineralization fractions of the total organic carbon were higher than 73%, while at the highest dose there was a reduction in the mineralization of organic matter by 17% and 63%, respectively in samples collected in layer 10-15 cm from the VF-CW and in the septic tank sludge dewatered in the drying bed.

A three-dimensional microenvironment alters CD73 expression in cervical cancer.

Stem-like cells (CSCs) have a tumour-initiating capacity and play critical role in tumour metastasis, relapse and resistance to therapy. The ectoenzyme CD73, encoded by the NT5E gene, which catalyses the hydrolysis of AMP into adenosine, has been associated to an immunosuppressive tumour microenvironment, tumour cell adhesion and migration. Therefore, we investigated the expression and activity of CD73 in sphere-forming cells from cervical cancer in comparison to monolayer cells in vitro. In addition, in silico analysis was performed to determine the expression of CD73 and other members of purinergic signalling in CSC-like population derived from different tumour types in comparison to monolayer cells. CD73 protein expression levels and functionality in SiHa cells were analysed by flow cytometry and enzymatic assay, respectively. In silico investigation was performed through the analysis of seven datasets from different tumour types using GEO database. In vitro analysis showed a decreased CD73 protein expression and enzymatic activity in cervical spheres, when compared to monolayers. In addition, when sphere-derived cells are re-plated as monolayer culture, the CD73 expression and activity are restored. Supporting the in vitro results, in silico analysis showed that three-dimensional spheres derived from cervical, thyroid and breast cancer presented decreased expression of CD73, when compared to their adherent counterparts. The decreased expression of CD73 in sphere-derived cells or CSC-enriched population reinforce its important role in cell adhesion, tumour spreading ability and metastasis, suggesting CD73 as potential target to be further investigated in cervical cancer.

Natural and Semisynthetic Pentacyclic Triterpenes for Chronic Myeloid Leukemia Therapy: Reality, Challenges and Perspectives.

Chronic myeloid leukemia (CML) is a neoplasm characterized by BCR-ABL1, an oncoprotein with vital role in leukemogenesis. Its inhibition by tyrosine kinase inhibitors represents the main choice of treatment. However, therapeutic failure is worrying given the lack of pharmacological options. Pentacyclic triterpenes are phytochemicals with outstanding antitumoral properties and have also been explored as a basis for the design of potential leads. In this review, we have gathered and discuss data regarding both natural and semisynthetic pentacyclic triterpenes applied to CML cell treatment. We found consistent evidence that the class of pentacyclic triterpenes in general exerts promising pro-apoptotic and antiproliferative activities in sensitive and resistant CML cells, and thus represents a rich source for drug development. We also analyze the predicted drug-like properties of the molecules, discuss the structural changes with biological implications and show the great opportunities this class represents, as well as the perspectives they provide on drug discovery for CML treatment.

Monte Carlo Simulations of the GE Signa PET/MR for Different Radioisotopes.

NEMA characterization of PET systems is generally based on 18F because it is the most relevant radioisotope for the clinical use of PET. 18F has a half-life of 109.7 min and decays into stable 18O via ß+ emission with a probability of over 96% and a maximum positron energy of 0.633 MeV. Other commercially available PET radioisotopes, such as 82Rb and 68Ga have more complex decay schemes with a variety of prompt gammas, which can directly fall into the energy window and induce false coincidence detections by the PET scanner. METHODS: Aim of this work was three-fold: (A) Develop a GATE model of the GE Signa PET/MR to perform realistic and relevant Monte Carlo simulations (B) Validate this model with published sensitivity and Noise Equivalent Count Rate (NECR) data for 18F and 68Ga (C) Use the validated GATE-model to predict the system performance for other PET isotopes including 11C, 15O, 13N, 82Rb, and 68Ga and to evaluate the effect of a 3T magnetic field on the positron range. RESULTS: Simulated sensitivity and NECR tests performed with the GATE-model for different radioisotopes were in line with literature values. Simulated sensitivities for 18F and 68Ga were 21.2 and 19.0/kBq, respectively, for the center position and 21.1 and 19.0 cps/kBq, respectively, for the 10 cm off-center position compared to the corresponding measured values of 21.8 and 20.0 cps/kBq for the center position and 21.1 and 19.6 cps/kBq for the 10 cm off-center position. In terms of NECR, the simulated peak NECR was 216.8 kcps at 17.40 kBq/ml for 18F and 207.1 kcps at 20.10 kBq/ml for 68Ga compared to the measured peak NECR of 216.8 kcps at 18.60 kBq/ml and 205.6 kcps at 20.40 kBq/ml for18F and 68Ga, respectively. For 11C, 13N, and 15O, results confirmed a peak NECR similar to 18F with the effective activity concentration scaled by the inverse of the positron fraction. For 82Rb, and 68Ga, the peak NECR was lower than for 18F while the corresponding activity concentrations were higher. For the higher energy positron emitters, the positron range was confirmed to be tissue-dependent with a reduction of the positron range by a factor of 3 to 4 in the plane perpendicular to the magnetic field and an increased positron range along the direction of the magnetic field. CONCLUSION: Monte-Carlo simulations were used to predict sensitivity and NECR performance of GE Signa PET/MR for 18F, 15O, 13N, 11C, 82Rb, and 68Ga radioisotopes and were in line with literature data. Simulations confirmed that sensitivity and NECR were influenced by the particular decay scheme of each isotope. As expected, the positron range decreased in the direction perpendicular to the 3T magnetic field. However, this will be only partially improving the resolution properties of a clinical PET/MR system due to the limiting spatial resolution of the PET detector.

The role of pain and disability changes after physiotherapy treatment on global perception of improvement in patients with chronic low back pain.

BACKGROUND: The effectiveness of physiotherapy in patients with chronic low back pain is usually measured through changes in pain and disability domains. However, recent research has suggested that these two domains are not sufficient to capture all the physiotherapy benefits when patients' perspective is considered. OBJECTIVE: The aim of this study was to investigate the role of pain and disability changes in explaining the global perception of improvement in patients with chronic low back pain undergoing physiotherapy. DESIGN: Prospective cohort study. METHODS: The study was conducted on183 patients who were referred to physiotherapy treatment due to low back pain lasting more than 12 weeks. Sociodemographic and clinical characteristics were measured at baseline, together with pain intensity and disability. Eight (post-intervention) and twelve weeks later, global perception of improvement was measured together with pain and disability. The Pearson correlation coefficient and linear regression models were used for analyses. RESULTS: Of the 183 participants included, 144 completed the 12-weeks follow-up. Significant and moderate correlation was found between pain and disability changes and the global perception of improvement after intervention and at the 12-weeks follow-up. Pain and disability changes explained 20.7%-36.3% of the variance in the global perception of improvement. CONCLUSIONS: Pain and disability changes are related and contributed to explaining a partial proportion of variance in the global perception of improvement. The findings suggest that these domains are not sufficient to explain and measure all of the benefits of physiotherapy when patients' global perception of improvement is considered.

Avaliação do perfil de mulheres atendidas em centros de referência em saúde de Porto Alegre/RS e relação de alterações citológicas detectadas no exame citopatológico e a presença do HPV / Profile evaluation of women that attended reference health centers in Porto Alegre/RS and the relationship between cytological alterations detected in cytopathological examination and presence of HPV / Evaluación del perfil de las mujeres atendidas en los centros de referencia de salud de Porto Alegre / RS y la relación de las alteraciones citológicas detectadas en el examen citopatológico con la presencia de VPH

Justificativas e Objetivos: Câncer de colo de útero é considerado um problema de saúde pública mundial. Seu diagnóstico é realizado através do exame citopatológico (EC) e seu desenvolvimento relacionado à infecção pelo papilomavírus humano (HPV). Este estudo objetiva avaliar o perfil de mulheres atendidas em centros de referência em saúde de Porto Alegre, Rio Grande do Sul, assim como a relação de alterações observadas ao EC com presença do HPV. Métodos: Estudo transversal realizado em mulheres atendidas em unidades básicas de saúde e um ambulatório de referência de hospital público terciário, no período de julho de 2014 a janeiro de 2017. Coletaram-se amostras representativas da endo/ectocérvice para realização do EC e investigadas quanto à presença molecular do HPV. Resultados: Foram analisadas 169 mulheres com idade média entre 31 e 40 anos, das quais 125 (74%) informaram que a sexarca ocorreu na faixa de 15-20 anos e 37,9% relatou ter tido de três a cinco parceiros sexuais. Em relação ao EC, 71 (42%) apresentaram resultado negativo para lesão intraepitelial ou malignidade e 98 (58%) alguma anormalidade de células escamosas: 20 (11,8%) atipias; 22 (13%) lesão intraepitelial escamosa de baixo grau e 56 (32,6%) lesão intraepitelial de alto grau (HSIL). Cinquenta (29,6%) apresentaram positividade para HPV, destas 56,4% foram diagnosticadas com HSIL (p<0,01). Conclusão: Os resultados revelam alta frequência de HPV em amostras com alterações citopatológicas, em mulheres jovens e com grau de exposição ao HPV, reforçando a importância do papel da sua identificação precoce na investigação da carcinogênese cervical.(AU)

Background and Objectives: Cervical cancer is considered a worldwide public health problem. Its diagnosis is made through cytopathological examination and its development related to human papillomavirus (HPV) infection. This study aims to evaluate the profile of women treated at reference health centers in Porto Alegre, Rio Grande do Sul, as well as the relation of changes observed to cytopathological examination with the presence of HPV. Methods: This is a cross-sectional study carried out in women treated at basic health units and a referral clinic of a public tertiary hospital, from July 2014 to January 2017. Representative samples of the endo/ectocervix were collected to perform the cytopathological examination and investigated for the molecular presence of HPV. Results: 169 women with mean age between 31 and 40 years were analyzed, of whom 125 (74%) reported that the onset of sexual activity occurred in the 15-20 years age group, and 37.9% reported having had three to five sexual partners. In relation to cytopathological examination, 71 (42%) had a negative result for intraepithelial lesion or malignancy and 98 (58%) some squamous cell abnormality: 20 (11.8%) atypical; 22 (13%) low-grade squamous intraepithelial lesion and 56 (32.6%) high-grade intraepithelial lesion (HSIL). Fifty (29.6%) were positive for HPV, of which 56.4% were diagnosed with HSIL (p < 0.01). Conclusion: The results reveal a high frequency of HPV in samples with cytopathological changes, in young women and with a degree of exposure to HPV, reinforcing the importance of the role of its early identification in the investigation of cervical carcinogenesis.(AU)

Justificación y objetivos: El cáncer de cuello uterino se considera un problema de salud pública en todo el mundo. Su diagnóstico se realiza mediante el examen citopatológico (EC), y su desarrollo está relacionado con la infección por el virus del papiloma humano (VPH). Este estudio objetivó evaluar el perfil de mujeres atendidas en los centros de referencia en salud de Porto Alegre, Rio Grande do Sul (Brasil), así como la relación de las alteraciones observadas en el EC con la presencia del VPH. Métodos: Estudio transversal realizado en las mujeres atendidas por unidades de atención primaria y por una clínica ambulatoria de referencia del hospital público terciario en la ciudad de Porto Alegre, en el período de julio de 2014 a enero de 2017. Se recolectaron muestras representativas de endo/ectocérvice para realizar la CE, las cuales se clasificaron según el sistema Bethesda y se investigaron la presencia molecular del VPH. Resultados: Analizamos 169 mujeres con promedio de edad entre 31 y 40 años, de las cuales 125 (74%) informaron que el sexarche ocurrió en el rango de 15-20 años. La mayoría (37,9%) informó haber tenido de 3 a 5 parejas sexuales; y el 37,3% estaban usando anticonceptivos orales. Con respecto a la EC, 71 (42%) se clasificaron como negativos para lesión intraepitelial o malignidad; y el 98 (58%) tenían alguna anormalidad de células escamosas: 20 (11,8%) de atipias; 22 (13,0%) lesión intraepitelial escamosa de bajo grado y 56 (32,6%) lesión intraepitelial de alto grado (HSIL). La frecuencia de positividad del VPH encontrada fue de 50 (29,6%), de estas un 56,4% fueron diagnosticadas con HSIL (p<0,01). Conclusiones: Estos resultados revelan una alta frecuencia de VPH en muestras con alteraciones citopatológicas presentes en mujeres jóvenes con cierto grado de exposición al VPH, lo que refuerza la importancia de identificarse tempranamente en el análisis de la carcinogénesis cervical.(AU)

Imatinib mesylate affects extracellular ATP catabolism and expression of NTPDases in a chronic myeloid leukemia cell line.

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm, characterized by the occurrence of the t(9;22)(q34;q11) translocation. First-line therapy for CML consists of treatment with imatinib mesylate, which selectively inhibits the BCR-ABL protein by competing for its ATP-binding site. Adenine nucleotide signaling is modulated by the ectonucleotidases and this pathway is related to tumorigenic processes. Considering the relationship between ATP and cancer, we aimed to evaluate the influence of imatinib mesylate on the expressions and functions of the NTPDase and ecto-5'-nucleotidase (CD73) enzymes in imatinib-sensitive and -resistant K-562 cell lines. mRNA analysis showed that K-562 cells express all ENTPDs and NT5E. However, when treated with imatinib mesylate for 24 h, the expression of ENTPD1, -2, -3 and -5 increased, leading to a higher nucleotides hydrolysis rate. HPLC analysis identified increased ATP degradation in cells after 24 h of treatment, with consequent ADP and AMP formation, corroborating the increase in gene and protein expression of ectonucleotidases as observed in previous results. On the other hand, we observed that imatinib-resistant K-562 cells presented a decrease in nucleotide hydrolysis and expressions of ENTPD1 and -5. These results suggest an involvement of imatinib in modulating ectonucleotidases in CML that will need further investigation. Since these ectonucleotidases have important catalytic activities in the tumor microenvironment, their modulation in CML cells may represent an important therapeutic approach to regulate levels of extracellular adenine nucleotides.

Impact of fast-track management on adult cardiac surgery: clinical and hospital outcomes. / Impacto do fast track em cirurgia cardíaca de adultos: desfechos clínicos e hospitalares.

OBJECTIVE: To compare the impact of two fast-track strategies regarding the extubation time and removal of invasive mechanical ventilation in adults after cardiac surgery on clinical and hospital outcomes. METHODS: This was a retrospective cohort study with patients undergoing cardiac surgery. Patients were classified according to the extubation time as the Control Group (extubated 6 hours after admission to the intensive care unit, with a maximum mechanical ventilation time of 18 hours), Group 1 (extubated in the operating room after surgery) and Group 2 (extubated within 6 hours after admission to the intensive care unit). The primary outcomes analyzed were vital capacity on the first postoperative day, length of hospital stay, and length of stay in the intensive care unit. The secondary outcomes were reintubation, hospital-acquired pneumonia, sepsis, and death. RESULTS: For the 223 patients evaluated, the vital capacity was lower in Groups 1 and 2 compared to the Control (p = 0.000 and p = 0.046, respectively). The length of stay in the intensive care unit was significantly lower in Groups 1 and 2 compared to the Control (p = 0.009 and p = 0.000, respectively), whereas the length of hospital stay was lower in Group 1 compared to the Control (p = 0.014). There was an association between extubation in the operating room (Group 1) with reintubation (p = 0.025) and postoperative complications (p = 0.038). CONCLUSION: Patients undergoing fast-track management with extubation within 6 hours had shorter stays in the intensive care unit without increasing postoperative complications and death. Patients extubated in the operating room had a shorter hospital stay and a shorter stay in the intensive care unit but showed an increase in the frequency of reintubation and postoperative complications.

OBJETIVO: Comparar o impacto de duas estratégias de fast track quanto ao momento de extubação e retirada da ventilação mecânica invasiva de adultos no pós-operatório cardíaco em desfechos clínicos e hospitalares. MÉTODOS: Estudo de coorte retrospectivo com pacientes submetidos à cirurgia cardíaca. Os pacientes foram classificados de acordo com o tempo de extubação em Grupo Controle (extubados após 6 horas de admissão na unidade de terapia intensiva, com tempo máximo de ventilação mecânica de 18 horas), Grupo 1 (extubados em sala de operação após término da cirurgia) e Grupo 2 (extubados em até 6 horas pós-admissão na unidade de terapia intensiva). Os desfechos primários analisados foram: capacidade vital no primeiro dia de pós-operatório, tempo de internamento hospitalar e na unidade de terapia intensiva. Os desfechos secundários foram reintubação, pneumonia adquirida no hospital, sepse e óbito. RESULTADOS: Para os 223 pacientes avaliados, a capacidade vital foi menor nos Grupos 1 e 2 comparados ao Controle (p = 0,000 e p = 0,046, respectivamente). Os dias de internamento em unidade de terapia intensiva foram significativamente menores nos Grupos 1 e 2 quando comparados ao Controle (p = 0,009 e p = 0,000, respectivamente), já os dias de internamento hospitalar foram menores no Grupo 1 quando comparado ao Controle (p = 0,014). Houve associação entre a extubação na sala de operação (Grupo 1) com reintubação (p = 0,025) e complicações pós-cirúrgicas (p=0,038). CONCLUSÃO: Pacientes submetidos ao fast track com extubação em até 6 horas apresentaram menor tempo de internamento em unidade de terapia intensiva sem aumentar complicações pós-cirúrgicas e óbito. Pacientes extubados em sala de operação tiveram menor tempo de internamento hospitalar e em unidade de terapia intensiva, mas apresentaram aumento na frequência de reintubação e complicações pós-cirúrgicas.

Impacto do fast track em cirurgia cardíaca de adultos: desfechos clínicos e hospitalares / Impact of fast-track management on adult cardiac surgery: clinical and hospital outcomes

RESUMO Objetivo: Comparar o impacto de duas estratégias de fast track quanto ao momento de extubação e retirada da ventilação mecânica invasiva de adultos no pós-operatório cardíaco em desfechos clínicos e hospitalares. Métodos: Estudo de coorte retrospectivo com pacientes submetidos à cirurgia cardíaca. Os pacientes foram classificados de acordo com o tempo de extubação em Grupo Controle (extubados após 6 horas de admissão na unidade de terapia intensiva, com tempo máximo de ventilação mecânica de 18 horas), Grupo 1 (extubados em sala de operação após término da cirurgia) e Grupo 2 (extubados em até 6 horas pós-admissão na unidade de terapia intensiva). Os desfechos primários analisados foram: capacidade vital no primeiro dia de pós-operatório, tempo de internamento hospitalar e na unidade de terapia intensiva. Os desfechos secundários foram reintubação, pneumonia adquirida no hospital, sepse e óbito. Resultados: Para os 223 pacientes avaliados, a capacidade vital foi menor nos Grupos 1 e 2 comparados ao Controle (p = 0,000 e p = 0,046, respectivamente). Os dias de internamento em unidade de terapia intensiva foram significativamente menores nos Grupos 1 e 2 quando comparados ao Controle (p = 0,009 e p = 0,000, respectivamente), já os dias de internamento hospitalar foram menores no Grupo 1 quando comparado ao Controle (p = 0,014). Houve associação entre a extubação na sala de operação (Grupo 1) com reintubação (p = 0,025) e complicações pós-cirúrgicas (p=0,038). Conclusão: Pacientes submetidos ao fast track com extubação em até 6 horas apresentaram menor tempo de internamento em unidade de terapia intensiva sem aumentar complicações pós-cirúrgicas e óbito. Pacientes extubados em sala de operação tiveram menor tempo de internamento hospitalar e em unidade de terapia intensiva, mas apresentaram aumento na frequência de reintubação e complicações pós-cirúrgicas.

ABSTRACT Objective: To compare the impact of two fast-track strategies regarding the extubation time and removal of invasive mechanical ventilation in adults after cardiac surgery on clinical and hospital outcomes. Methods: This was a retrospective cohort study with patients undergoing cardiac surgery. Patients were classified according to the extubation time as the Control Group (extubated 6 hours after admission to the intensive care unit, with a maximum mechanical ventilation time of 18 hours), Group 1 (extubated in the operating room after surgery) and Group 2 (extubated within 6 hours after admission to the intensive care unit). The primary outcomes analyzed were vital capacity on the first postoperative day, length of hospital stay, and length of stay in the intensive care unit. The secondary outcomes were reintubation, hospital-acquired pneumonia, sepsis, and death. Results: For the 223 patients evaluated, the vital capacity was lower in Groups 1 and 2 compared to the Control (p = 0.000 and p = 0.046, respectively). The length of stay in the intensive care unit was significantly lower in Groups 1 and 2 compared to the Control (p = 0.009 and p = 0.000, respectively), whereas the length of hospital stay was lower in Group 1 compared to the Control (p = 0.014). There was an association between extubation in the operating room (Group 1) with reintubation (p = 0.025) and postoperative complications (p = 0.038). Conclusion: Patients undergoing fast-track management with extubation within 6 hours had shorter stays in the intensive care unit without increasing postoperative complications and death. Patients extubated in the operating room had a shorter hospital stay and a shorter stay in the intensive care unit but showed an increase in the frequency of reintubation and postoperative complications.

Chemistry and Pharmacology of the Kazakh Crataegus Almaatensis Pojark: An Asian Herbal Medicine.

Crataegus almaatensis, an endemic ornamental plant in Kazakhstan is used in popular medicine due to its cardiotonic properties. The most studied species of the same genus are commonly found in Europe, which shows the importance of having the Kazakh species validated via its chemical and pharmacological studies. High-speed countercurrent chromatography (HSCCC) operated under optimized conditions enabled an isolation of the three main compounds from the aqueous phase of the leaves ethanol extract, further identified by nuclear magnetic resonance (NMR), as quercetin 3-O-rhamnoside (quercitrin) (4.02% of the crude extract-CECa); quercetin 3-O-ß-galactoside (hyperoside) (1.82% of CECa); kaempferol 3-O-α-L-rhamnoside (afzelin) (0.94% of CECa). The CECa, the aqueous phase of the crude extract (APCa) together with the isolates were evaluated for their vascular (vascular reactivity in human internal mammary artery-HIMA), anti-nociceptive (formalin-induced liking response and hot plate) and anti-inflammatory (subcutaneous air-pouch model-SAP) activities. CECa at the concentrations of 0.014 and 0.14 mg/mL significantly increased the maximum contractility response of HIMA to noradrenaline. The APCa CR curve (0.007-0.7 mg/mL) showed an intrinsic relaxation effect of the HIMA. APCa at the dose of 100 mg/kg i.p. significantly decreased the total leukocyte count and the IL-1ß release in the SAP wash.

Diagnostic Accuracy of CD64 for Sepsis in Emergency Department.

INTRODUCTION: Sepsis is a systemic inflammatory response to suspected or confirmed infection. Clinical evaluations are essential for its early detection and treatment. Blood cultures may take as long as 2 days to yield a result and are not always reliable. However, recent studies have suggested that neutrophil CD64 expression may be a sensitive and specific alternative for the diagnosis of systemic infection. OBJECTIVE: The objective of the study was to analyze the difference in CD64 values between subjects with systemic inflammatory response syndrome (SIRS), suspected or confirmed sepsis, who meet diagnostic criteria for SIRS upon arriving at an emergency department. MATERIALS AND METHODS: This was a prospective observational cohort study, an accuracy study of CD64 prospectively evaluated. The sample consisted of 109 patients aged 18 years with criteria for SIRS on arrival to emergency department. CD64 expression was measured within 6 h of hospital admission and once again after 48 h. RESULTS: ROC curve analysis suggested that a cutoff of 1.45 for CD64 expression could diagnose sepsis with a sensitivity of 0.85, a specificity of 0.75, an accuracy of 82.08%, a positive predictive value of 0.96, a negative predictive value of 0.38 and a positive likelihood ratio of 3.33. The area under the curve was 0.83. CONCLUSION: CD64 seems to be a useful, sensitive, and specific biomarker in discriminating between SIRS and sepsis.

Aneurysm of the Fenestrated Basilar Artery: Case Report and Literature Review

Introduction Aneurysms of the vertebrobasilar junction are rare, but when present, they are often associated with fenestration of the basilar artery. Frequently, the endovascular treatment is the first choice due to the complex anatomy of the posterior fossa, which represents a challenge for the open surgical treatment alternative. Case Report A 47-year-old man was admitted to the emergency unit with headache, diplopia, neck pain and mental confusion. The neurological exam showed: score of 15 in the Glasgow coma scale (GCS), no motor or sensitivity deficit, palsy of the left sixth cranial nerve and Hunt-Hess grade III. The computed tomography (CT) scan showed subarachnoid hemorrhage (Fisher III) and hydrocephalus. The patient was submitted to ventricular-peritoneal shunt. A diagnostic arteriography was performed with 3D reconstruction, which showed evidence of fenestration of the basilar artery associated with aneurysm in the right vertebrobasilar portion. An aneurysm coil embolization was performed without complications. The patient was discharged 19 days later maintaining diplopia, with paralysis of the left sixth cranial nerve, but without any other complaints or neurological symptoms. Discussion Fenestration of the basilar artery occurs due to failure of fusion of the longitudinal neural arteries in the embryonic period, and it is associated with the formation of aneurysms. The endovascular treatment is the first choice and several techniques are described, including simple coiling, balloon remodeling, stent-assisted coiling, liquid embolic agents and flow diversion devices. The three-dimensional rotational angiography (3DRA) is an extremely helpful tool when planning the best treatment course. Conclusion Fenestrated basilar artery aneurysms are rare and complex vascular diseases and their treatment improved with the advent of the 3D angiography and the development of the endovascular techniques.

Introdução Aneurismas da junção vertebrobasilar são raros, mas quando presentes, geralmente estão associados à fenestração da artéria basilar. Frequentemente, o tratamento endovascular é a primeira opção devido à complexidade da anatomia da fossa posterior, o que representa um obstáculo para a alternativa de tratamento com cirurgia aberta. Relato de Caso Um homem de 47 anos de idade deu entrada na unidade de emergência com cefaleia, diplopia, dor no pescoço e desorientação. O exame neurológico mostrou: 15 pontos na escala de coma Glasgow (ECG), ausência de déficit motor ou de sensibilidade, paralisia do sexto nervo craniano I esquerdo, Hunt-Hess grau III. A tomografia computadorizada apresentou hemorragia subaracnoidea (Fisher grau III) e hidrocefalia. O paciente foi submetido a shunt ventricular-peritoneal. A arteriografia diagnóstica foi feita com reconstrução 3D, que comprovou fenestração da artéria basilar associada a aneurisma na porção vertebrobasilar direita. Realizamos embolização do aneurisma com molas, sem complicações. O paciente recebeu alta 19 dias depois, mantendo diplopia, paralisia do sexto nervo craniano esquerdo, sem outras complicações ou sintomas neurológicos. Discussão A fenestração da artéria basilar ocorre devido à falência da fusão das artérias neurais longitudinais no período embrionário e está associada à formação de aneurismas. O tratamento endovascular é a primeira opção e várias técnicas são descritas, incluindo simples embolização, remodelagem por balão, embolização assistida com stent, agentes embólicos líquidos e dispositivos de desvio de fluxo. Para planejar o melhor tratamento, angiografias rotacionais 3D são extremamente úteis. Conclusão Aneurismas de artéria basilar fenestrada são doenças vasculares raras e complexas, e seu tratamento foi aprimorado com o advento de angiografias 3D e desenvolvimento de técnicas endovasculares.

Study of the removal mechanism of aquatic emergent pollutants by new bio-based chars.

This work is dedicated to study the potential application of char byproducts obtained in the gasification of rice husk (RG char) and rice husk blended with corn cob (RCG char) as removal agents of two emergent aquatic contaminants: tetracycline and caffeine. The chars presented high ash contents (59.5-81.5%), being their mineral content mainly composed of silicon (as silica) and potassium. The samples presented a strong basic character, which was related to its higher mineral oxides content. RCG char presented better textural properties with a higher apparent surface area (144 m2 g-1) and higher micropore content (V micro = 0.05 cm3 g-1). The alkaline character of both chars promoted high ecotoxicity levels on their aqueous eluates; however, the ecotoxic behaviour was eliminated after pH correction. Adsorption experiments showed that RG char presented higher uptake capacity for both tetracycline (12.9 mg g-1) and caffeine (8.0 mg g-1), indicating that textural properties did not play a major role in the adsorption process. For tetracycline, the underlying adsorption mechanism was complexation or ion exchange reactions with the mineral elements of chars. The higher affinity of RG char to caffeine was associated with the higher alkaline character presented by this char.

Differentiation of Candida albicans, Candida glabrata, and Candida krusei by FT-IR and chemometrics by CHROMagar™ Candida.

Pathogenic Candida species are detected in clinical infections. CHROMagar™ is a phenotypical method used to identify Candida species, although it has limitations, which indicates the need for more sensitive and specific techniques. Infrared Spectroscopy (FT-IR) is an analytical vibrational technique used to identify patterns of metabolic fingerprint of biological matrixes, particularly whole microbial cell systems as Candida sp. in association of classificatory chemometrics algorithms. On the other hand, Soft Independent Modeling by Class Analogy (SIMCA) is one of the typical algorithms still little employed in microbiological classification. This study demonstrates the applicability of the FT-IR-technique by specular reflectance associated with SIMCA to discriminate Candida species isolated from vaginal discharges and grown on CHROMagar™. The differences in spectra of C. albicans, C. glabrata and C. krusei were suitable for use in the discrimination of these species, which was observed by PCA. Then, a SIMCA model was constructed with standard samples of three species and using the spectral region of 1792-1561cm-1. All samples (n=48) were properly classified based on the chromogenic method using CHROMagar™ Candida. In total, 93.4% (n=45) of the samples were correctly and unambiguously classified (Class I). Two samples of C. albicans were classified correctly, though these could have been C. glabrata (Class II). Also, one C. glabrata sample could have been classified as C. krusei (Class II). Concerning these three samples, one triplicate of each was included in Class II and two in Class I. Therefore, FT-IR associated with SIMCA can be used to identify samples of C. albicans, C. glabrata, and C. krusei grown in CHROMagar™ Candida aiming to improve clinical applications of this technique.

Comparison of cyclophosphamide-thalidomide-dexamethasone to bortezomib-cyclophosphamide-dexamethasone as induction therapy for multiple myeloma patients in Brazil.

OBJECTIVE/BACKGROUND: Chemotherapy followed by autologous hematopoietic stem cell transplantation (HSCT) remains the standard treatment for multiple myeloma (MM). Thalidomide or bortezomib may be combined with cyclophosphamide and dexamethasone, in what are known as the CTD and VCD protocols, respectively. The objective of this study was to evaluate the clinical characteristics and response rates obtained with CTD and VCD, observing whether the inclusion of bortezomib to treat MM patients in Brazil increases therapeutic efficiency. METHODS: Forty-three MM patients treated with induction protocols CTD and VCD between January 2010 and March 2015 were included. The parameters analyzed were staging, frequency of comorbidities prior to treatment, response rates obtained at each induction cycle, progression-free survival, and overall survival of patients. RESULTS: Very good partial response and complete response obtained with the VCD protocol were superior, compared with the CTD treatment. The presence of comorbidities was similar in the two groups, except kidney failure, which prevailed in the VCD group. Also, 78.3% and 48.3% of patients treated with the VCD and CTD protocols underwent autologous HSCT, respectively. In patients given the VCD protocol, 45.5% had complete response before autologous HSCT. Among those given CTD, this number was only 7.1% (p=0.023). Disease progression after autologous HSCT did not differ between the two groups. CONCLUSION: VCD afforded better responses than the CTD protocol, and improved patient condition before autologous HSCT. However, more studies are necessary including more patients and addressing various clinical conditions, besides the analysis of cost-effectiveness of these treatments.