Current oral hygiene and recreational behavioral trends in HIV disease.

OBJECTIVE: HIV disease is evolving with more HIV+ persons experiencing a high quality of life with well-controlled viremia. We recently enrolled a large cohort of HIV+ and clinically relevant HIV- persons for oral microbiome analyses that included a questionnaire related to oral hygiene and recreational behaviors. Here, the questionnaire responses were analyzed for behavioral trends within the cohort, together with trends over time by comparison to a previous geographically centered HIV+ cohort. METHODS: Data were collected by questionnaire at baseline visits as cross-sectional assessments. Multivariable analyses were conducted for associations of HIV status as well as age, race, and sex, on oral hygiene/recreational behaviors. RESULTS: HIV+ subjects had reduced brushing frequency, but increased incidence of past cleanings and frequency of dry mouth, compared to the HIV- subjects. Within the entire cohort, positive associations were identified between age and several oral hygiene practices, and between age, race, and sex for several recreational behaviors. In comparison to the historical cohort, the contemporary HIV+ cohort participated in fewer high-risk behaviors, but with similar trends for smoking and oral hygiene practices. CONCLUSION: HIV status had little association with oral hygiene and recreational behaviors despite several differences in age, race, and sex. Behavioral trends over time support a higher quality of life in people currently living with HIV.

Synthesis of gold decorated silica nanoparticles and their photothermal properties.

Silica-Gold Nanostructures (SGNs), composed of a silica core decorated by gold nanoparticles, have the photothermal capacity to transform near-infrared (NIR) wavelengths into heat. This work presents a simple, efficient, and replicable method of synthesis of SGNs and their characterization by: (1) transmission electron microscopy to obtain micrographs of the particles and their corresponding diameter distribution; (2) diffraction patterns showing the amorphous atomic arraignment of the silica and the crystalline atomic arrangement of the gold nanoparticles; (3) zeta potential confirming the stability of the SGNs in a colloidal solution; and (4) thermal images displaying the capacity of SGNs to convert NIR irradiation into heat and their respective increment in temperature. SGNs were synthesized over silica cores with diameters of 63, 83, and 132 nm and decorated with a partial gold shell. They were heated with a coherent light intensity of 340 mW/cm2 with a wavelength of 852 nm. This wavelength is within the range of the optical window of the human body; therefore, SGNs may be used for the photothermal ablation of tumors with no damage to the tissue. The heating of different dimensions of SGNs took 6-8 min of NIR radiation, and their cooling, once the laser was turned off, was in the order of 2-3 min. It was found that SGNs, with a core diameter of 132 nm, have a notable photothermal capacity. That enables them to increase the temperature of their surroundings by 4.4 ºC. This increment in temperature is sufficient to induce cellular necrosis, which makes SGNs a good option for photothermal treatments.

Antitumor activity of copper(II) complexes with Schiff bases derived from N'-tosylbenzene-1,2-diamine.

The electrochemical oxidation of anodic metal copper in a solution of the ligands N-[(5-tert-butyl-2-hydroxyphenyl)methylidine]-N'-tosylbenzene-1,2-diamine [H2L1] and N-[(3,5-di-tert-butyl-2-hydroxyphenyl)methylidine]-N'-tosylbenzene-1,2-diamine, [H2L2] afforded homoleptic [CuL] compounds or solvate [CuLS] complexes. The addition to the electrochemical cell of coligands (L') such as 2,2'-bipyridine (2-bpy), 4,4'-bipyridine(4-bpy) or 1,10-phenanthroline (phen) allowed the synthesis, in one step, of heteroleptic [CuLL'] compounds, namely [CuL1(H2O)] (1), [CuL1(2,2'-bpy)]⋅CH3CN (2), [CuL1(phen)]·H2O (3), [Cu2L12(4,4'-bpy)] (4), [CuL2(CH3OH)] (5), [CuL2(2,2'-bpy)] (6), [CuL2(phen)] (7) and [Cu2L22(4,4'-bpy)] (8). The crystal structures of both ligands, H2L1, H2L2, and those of the complexes (2), (4), (5), (6) and (7) have been determined by X-ray diffraction techniques. Coordination polyhedron around metal atom is square planar for [CuL2(CH3OH)] (5) and [Cu2L12(4,4'-bpy)] (4) and square pyramid for the other complexes with additional chelating ligands. The cytotoxic activity of this new series of copper(II) complexes against the SH-SY5Y neuroblastoma cell line and U87-MG and U373-MG glioblastoma cell lines has been investigated. Most of the test compounds showed higher activity than cisplatin in the three cell lines. Among this series, compound [CuL1(phen)] (3) displayed the highest activity with IC50 equal to 1.77 µM on SH-SY5Y whereas compound [Cu2L12(4.4'-bpy)] (4) resulted the most potent compounds on U87 MG and U373 MG glioblastoma cell lines. Studies on the cytotoxic activity of these derivatives suggest that these compounds induce cell death by a mechanism other than apoptosis.

Metastasis of melanoma in non-sentinel nodes in patients with metastatic sentinel node. Can we avoid complementary lymphadenectomy?

BACKGROUND: Lymph mapping with sentinel node biopsy is the standard procedure for lymph node staging in patients with cutaneous melanoma with a tumor thickness of 1 mm or greater. Patients who have metastases in sentinel node must undergo complementary lymphadenectomy; however, it has not been shown to improve survival. OBJECTIVE: To know the prevalence in our setting of metastases in the product of complementary lymphadenectomy in patients with metastatic sentinel node. METHOD: Evaluation of a descriptive, retrospective, observational and analytical cohort of patients with metastatic sentinel node submitted to lymphadenectomy. Multivariate analysis of tumor thickness, neural invasion, location, sentinel node number, serum DHL level, lymph nodes dissected and extracapsular spread. RESULTS: 67 patients, 35 women and 32 men with a mean of 66 years, 22% had metastases in lymph nodes from complementary lymphadenectomy, 19% of them with extracapsular spread; no relationship with the Breslow level. Extracapsular spread in the sentinel node, lymphadenectomy time, and perineural invasion in the primary tumor were prognostic factors for non-sentinel node metastasis. CONCLUSIONS: In this series, 22% of the patients with a sentinel node-positive have metastases in the non-sentinel nodes, 19% of them with extracapsular spread, which justifies complementary lymphadenectomy.

ANTECEDENTES: El mapeo linfático con biopsia del ganglio centinela es el procedimiento estándar de estadificación ganglionar en pacientes con melanoma cutáneo con grosor tumoral de 1 mm o mayor. Los pacientes que tienen metástasis en él deben ser sometidos a linfadenectomía complementaria; sin embargo, esta no ha mostrado mejorar la superviviencia. OBJETIVO: Conocer la prevalencia en nuestro medio de metástasis en el producto de linfadenectomía complementaria en pacientes con ganglio centinela metastásico. MÉTODO: Evaluación de una cohorte descriptiva, retrospectiva, observacional y analítica de pacientes con ganglio centinela metastásico sometidos a linfadenectomía, con análisis multivariado de grosor tumoral, invasión neural, localización, número de ganglios centinela, concentración sérica de deshidrogenasa láctica, ganglios disecados en linfadenectomía y ruptura capsular. RESULTADOS: Hubo 67 pacientes (35 mujeres y 32 hombres), con una media de 66 años de edad, en el 22% hubo metástasis en ganglios de linfadenectomía complementaria y en el 19% ruptura capsular; sin relación con el nivel de Breslow. La ruptura capsular en el ganglio centinela, el tiempo de linfadenectomía y la invasión perineural fueron factores pronóstico de metástasis en ganglios no centinela. CONCLUSIONES: En esta serie, el 22% de los pacientes tuvieron metástasis en ganglios no centinela, el 19% de ellos con ruptura capsular, lo cual justifica la linfadenectomía complementaria.

Multifunctional PLA/Gelatin Bionanocomposites for Tailored Drug Delivery Systems.

A series of bionanocomposites composed of shark gelatin hydrogels and PLA nanoparticles featuring different nanostructures were designed to generate multifunctional drug delivery systems with tailored release rates required for personalized treatment approaches. The global conception of the systems was considered from the desired customization of the drug release while featuring the viscoelastic properties needed for their ease of storage and posterior local administration as well as their biocompatibility and cell growth capability for the successful administration at the biomolecular level. The hydrogel matrix offers the support to develop a direct thermal method to convert the typical kinetic trapped nanostructures afforded by the formulation method whilst avoiding the detrimental nanoparticle agglomeration that diminishes their therapeutic effect. The nanoparticles generated were successfully formulated with two different antitumoral compounds (doxorubicin and dasatinib) possessing different structures to prove the loading versatility of the drug delivery system. The bionanocomposites were characterized by several techniques (SEM, DLS, RAMAN, DSC, SAXS/WAXS and rheology) as well as their reversible sol-gel transition upon thermal treatment that occurs during the drug delivery system preparation and the thermal annealing step. In addition, the local applicability of the drug delivery system was assessed by the so-called "syringe test" to validate both the storage capability and its flow properties at simulated physiological conditions. Finally, the drug release profiles of the doxorubicin from both the PLA nanoparticles or the bionanocomposites were analyzed and correlated to the nanostructure of the drug delivery system.

Elevated Cytokine Levels in Plasma of Patients with SARS-CoV-2 Do Not Contribute to Pulmonary Microvascular Endothelial Permeability.

The vascular endothelial injury occurs in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, but the mechanisms are poorly understood. We sought to determine the frequency and type of cytokine elevations and their relationship to endothelial injury induced by plasma from patients with SARS-CoV-2 versus controls. Plasma from eight consecutively enrolled patients hospitalized with acute SARS-CoV-2 infection was compared to controls. Endothelial cell (EC) barrier integrity was evaluated using ECIS (electric cell-substrate impedance sensing) on human lung microvascular EC. Plasma from all SARS-CoV-2 but none from controls decreased transendothelial resistance to a greater degree than that produced by tumor necrosis factor-alpha (TNF-α), the positive control for the assay. Thrombin, angiopoietin 2 (Ang2), and vascular endothelial growth factor (VEGF), complement factor C3a and C5a, and spike protein increased endothelial permeability, but to a lesser extent and a shorter duration when compared to SARS-CoV-2 plasma. Analysis of Ang2, VEGF, and 15 cytokines measured in plasma revealed striking patient-to-patient variability within the SARS-CoV-2 patients. Pretreatment with thrombin inhibitors, single, or combinations of neutralizing antibodies against cytokines, Ca3 and C5a receptor antagonists, or with ACE2 antibody failed to lessen the SARS-CoV-2 plasma-induced EC permeability. The EC barrier destructive effects of plasma from patients with SARS-CoV-2 were susceptible to heat inactivation. Plasma from patients hospitalized with acute SARS-CoV-2 infection uniformly disrupts lung microvascular integrity. No predicted single, or set of, cytokine(s) accounted for the enhanced vascular permeability, although the factor(s) were heat-labile. A still unidentified but potent circulating factor(s) appears to cause the EC disruption in SARS-CoV-2 infected patients. IMPORTANCE Lung vascular endothelial injury in SARS-CoV-2 patients is one of the most important causes of morbidity and mortality and has been linked to more severe complications including acute respiratory distress syndrome (ARDS) and subsequent death due to multiorgan failure. We have demonstrated that in eight consecutive patients with SARS-CoV-2, who were not selected for evidence of endothelial injury, the diluted plasma-induced intense lung microvascular damage, in vitro. Known endothelial barrier-disruptive agents and proposed mediators of increased endothelial permeability in SARS-CoV-2, induced changes in permeability that were smaller in magnitude and shorter in duration than plasma from patients with SARS-CoV-2. The effect on endothelial cell permeability of plasma from patients with SARS-CoV-2 was heat-labile. The main plasma factor that causes the increased endothelial permeability remains to be identified. Our study provides a possible approach for future studies to understand the underlying mechanisms leading to vascular injury in SARS-CoV-2 infections.

Effect of HIV/HAART and Other Clinical Variables on the Oral Mycobiome Using Multivariate Analyses.

The oral microbiome is considered an important factor in health and disease. We recently reported significant effects of HIV and several other clinical variables on the oral bacterial communities in a large cohort of HIV-positive and -negative individuals. The purpose of the present study was to similarly analyze the oral mycobiome in the same cohort. To identify fungi, the internal transcribed spacer 2 (ITS2) of the fungal rRNA genes was sequenced using oral rinse samples from 149 HIV-positive and 88 HIV-negative subjects that had previously undergone bacterial amplicon sequencing. Quantitative PCR was performed for total fungal content and total bacterial content. Interestingly, samples often showed predominance of a single fungal species with four major clusters predominated by Candida albicans, Candida dubliniensis, Malassezia restricta, or Saccharomyces cerevisiae Quantitative PCR analysis showed the Candida-dominated sample clusters had significantly higher total fungal abundance than the Malassezia or Saccharomyces species. Of the 25 clinical variables evaluated for potential influences on the oral mycobiome, significant effects were associated with caries status, geographical site of sampling, sex, HIV under highly active antiretroviral therapy (HAART), and missing teeth, in rank order of statistical significance. Investigating specific interactions between fungi and bacteria in the samples often showed Candida species positively correlated with Firmicutes or Actinobacteria and negatively correlated with Fusobacteria, Proteobacteria, and Bacteroidetes Our data suggest that the oral mycobiome, while diverse, is often dominated by a limited number of species per individual; is affected by several clinical variables, including HIV positivity and HAART; and shows genera-specific associations with bacterial groups.IMPORTANCE The oral microbiome is likely a key element of homeostasis in the oral cavity. With >600 bacterial species and >160 fungal species comprising the oral microbiome, influences on its composition can have an impact on both local and systemic health. We recently reported significant effects of HIV and several other clinical variables on the oral bacterial community in a large cohort of HIV-positive and -negative subjects. We describe here a comprehensive analysis of the oral mycobiome in the same cohort. Similar to the bacterial community, HIV under highly active antiretroviral therapy (HAART) had a significant impact on the mycobiome composition, but with less impact compared to other clinical variables. Additionally, unlike the oral bacterial microbiome, the oral mycobiome is often dominated by a single species with 4 major clusters of fungal communities. Together, these results suggest the oral mycobiome has distinct properties compared with the oral bacterial community, although both are equally impacted by HIV.

Perioperative Considerations in Urgent Surgical Care of Suspected and Confirmed COVID-19 Orthopaedic Patients: Operating Room Protocols and Recommendations in the Current COVID-19 Pandemic.

By April 7, 2020, severe acute respiratory syndrome coronavirus 2 was responsible for 1,383,436 confirmed cases of Coronavirus disease 2019 (COVID-19), involving 209 countries around the world; 378,881 cases have been confirmed in the United States. During this pandemic, the urgent surgical requirements will not stop. As an example, the most recent Centers of Disease Control and Prevention reports estimate that there are 2.8 million trauma patients hospitalized in the United States. These data illustrate an increase in the likelihood of encountering urgent surgical patients with either clinically suspected or confirmed COVID-19 in the near future. Preparation for a pandemic involves considering the different levels in the hierarchy of controls and the different phases of the pandemic. Apart from the fact that this pandemic certainly involves many important health, economic, and community ramifications, it also requires several initiatives to mandate what measures are most appropriate to prepare for mitigating the occupational risks. This article provides evidence-based recommendations and measures for the appropriate personal protective equipment for different clinical and surgical activities in various settings. To reduce the occupational risk in treating suspected or confirmed COVID-19 urgent orthopaedic patients, recommended precautions and preventive actions (triage area, emergency department consultation room, induction room, operating room, and recovery room) are reviewed.

Coumarin-grafted blue-emitting fluorescent alginate as a potentially valuable tool for biomedical applications.

A novel blue-emitting fluorescent alginate derivative has been successfully synthesised in a simple two-reaction step procedure, using an aqueous conjugation strategy that involved carbodiimide coupling followed by an alkyne-azide "click" reaction. The modified alginate maintained the characteristic ability to form mechanically stable hydrogels by ionic crosslinking. The fluorescent properties of the developed biomaterial were investigated both in solution and hydrogel states, revealing that grafting of the coumarin fluorophore to alginate greatly enhanced its fluorescent properties. Importantly, hydrogels maintained around 80% of their initial fluorescence upon long periods of incubation under physiologic conditions. The fluorescent alginate hydrogels showed to be biocompatible in vitro, supporting the viability, metabolic activity and proliferation of mammary epithelial cells and, more importantly, their morphogenesis into spheroids and polarized acini-like structures. These hydrogels were further applied in the establishment of cell-in-gel microarrays for high-throughput screening of cell behaviour in three-dimensional (3D) matrices, being essential for spotting optimization and analysis. Collectively, our results highlight the potential of coumarin-grafted blue-emitting fluorescent alginate as a valuable tool for biomedical applications where hydrogel tracing is required.

Significant effect of HIV/HAART on oral microbiota using multivariate analysis.

Persons infected with HIV are particularly vulnerable to a variety of oral microbial diseases. Although various study designs and detection approaches have been used to compare the oral microbiota of HIV-negative and HIV-positive persons, both with and without highly active antiretroviral therapy (HAART), methods have varied, and results have not been consistent or conclusive. The purpose of the present study was to compare the oral bacterial community composition in HIV-positive persons under HAART to an HIV-negative group using 16S rRNA gene sequence analysis. Extensive clinical data was collected, and efforts were made to balance the groups on clinical variables to minimize confounding. Multivariate analysis was used to assess the independent contribution of HIV status. Eighty-nine HIV-negative participants and 252 HIV-positive participants under HAART were sampled. The independent effect of HIV under HAART on the oral microbiome was statistically significant, but smaller than the effect of gingivitis, periodontal disease, smoking, caries, and other clinical variables. In conclusion, a multivariate comparison of a large sample of persons with HIV under HAART to an HIV-negative control group showed a complex set of clinical features that influenced oral bacterial community composition, including the presence of HIV under HAART.

Cervical metastasis of squamous cell carcinoma of the head and neck. Therapeutic options.

INTRODUCTION: Patients with bulky metastases of squamous cell carcinoma of the head and neck represent a challenge for the therapeutic decision; balance between oncological control and complications should be achieved. The therapeutic sequence has no impact on survival but sequelae. OBJECTIVE: We analyze the oncological results in patients with bulky metastases on the neck treated with induction chemotherapy and with up-front neck dissection. METHOD: Retrospective analysis of patients undergoing treatment for cervical lymph node metastasis of squamous cell carcinoma; The therapeutic sequence was decided based on volume, resectability, site, and size of the primary and general condition of the patient. Overall survival was calculated based on human papilloma virus (HPV) status. RESULTS: There were 30 patients, 22 men and eight women with a mean age of 57 years, 10 N3 and 20 N2. In 13 the HPV was positive, in 5 negative and in 12 the determination was not made. Seven patients were treated with initial chemotherapy, and 23 underwent neck dissection; the 5-year survival was 25%, and the prognosis was better in the positive HPV. CONCLUSION: The treatment of cervical metastasis depends on the possibility of resection. We should favor the initial surgery. The HPV is a factor of good prognosis.

INTRODUCCIÓN: Los pacientes con metástasis voluminosas de carcinoma epidermoide de cabeza y cuello representan un reto para la decisión terapéutica; se debe lograr un equilibrio entre el control oncológico y las complicaciones. La secuencia terapéutica no tiene impacto en la supervivencia, pero sí en las secuelas. OBJETIVO: Conocer los resultados oncológicos de pacientes con metástasis en el cuello tratados con cirugía inicial y con quimioterapia de inducción. MÉTODO: Análisis retrospectivo de pacientes sometidos a tratamiento por metástasis ganglionares cervicales de carcinoma epidermoide. La secuencia terapéutica se decidió basándose en el volumen, la resecabilidad, el sitio y el tamaño del tumor primario, y el estado general del paciente. Se calculó la supervivencia global y según el estado de portador o no del virus del papiloma humano (VPH). RESULTADOS: Se incluyeron 30 pacientes, 22 hombres y 8 mujeres, con una media de edad de 57 años. En cuanto al estadio, 10 eran N3 y 20 eran N2. En 13 el VPH fue positivo, en 5 fue negativo y en 12 no se efectuó la determinación. Siete pacientes fueron tratados con quimioterapia inicial y 23 fueron sometidos a disección de cuello. La supervivencia a 5 años fue del 25% y el pronóstico fue mejor en los VPH positivos. CONCLUSIÓN: El tratamiento de las metástasis cervicales depende de su resecabilidad. Hay que favorecer la cirugía inicial. El VPH es un factor de buen pronóstico.

A Mycoses Study Group International Prospective Study of Phaeohyphomycosis: An Analysis of 99 Proven/Probable Cases.

BACKGROUND: Phaeohyphomycosis is infection caused by dematiaceous, or darkly pigmented, fungi. The spectrum of disease is broad, and optimal therapy remains poorly defined. The Mycoses Study Group established an international case registry of patients with proven/probable phaeohyphomycosis with the goal of improving the recognition and management of these infections. METHODS: Patients from 18 sites in 3 countries were enrolled from 2009-2015. Cases were categorized as local superficial, local deep (pulmonary, sinus, osteoarticular infections), and disseminated infections. End points were clinical response (partial and complete) and all-cause mortality at 30 days and end of follow-up. RESULTS: Of 99 patients, 32 had local superficial infection, 41 had local deep infection, and 26 had disseminated infection. The most common risk factors were corticosteroids, solid organ transplantation, malignancy, and diabetes. Cultures were positive in 98% of cases. All-cause mortality was 16% at 30 days and 33% at end of follow-up, and 18 of 26 (69%) with dissemination died. Itraconazole was most commonly used for local infections, and voriconazole was used for more severe infections, often in combination with terbinafine or amphotericin B. CONCLUSIONS: Phaeohyphomycosis is an increasingly recognized infection. Culture remains the most frequently used diagnostic method. Triazoles are currently the drugs of choice, often combined with other agents. Further studies are needed to develop optimal therapies for disseminated infections.

Surgical prophylaxis with gram-negative activity for reduction of surgical site infections after microvascular reconstruction for head and neck cancer.

BACKGROUND: The purpose of this study was to determine the incidence of and risk factors for surgical site infections in microvascular reconstruction for patients with head and neck cancer. METHODS: One hundred seventeen patients with head and neck cancer undergoing microvascular reconstruction received postoperative surgical infection prophylaxis and were followed for 30 days. Surgical infection prophylaxis was categorized by empiric spectrum of activity. Risk factors for surgical site infection development and cumulative incidence of surgical site infections were characterized. RESULTS: Thirty-seven patients developed surgical site infection (cumulative surgical site infection incidence of 31.6%). Risk factors identified in logistic regression include alcohol use (odds ratio [OR] = 2.704; 95% confidence interval [CI] = 1.029-7.106), increased surgical duration (OR = 1.403; 95% CI = 1.185-1.661), American Society of Anesthesiologists (ASA) class IV (OR = 3.075; 95% CI = 1.000-9.459), and lack of postoperative gram-negative coverage (OR = 15.139; 95% CI = 3.083-74.347). CONCLUSION: Alcohol use, longer surgical duration, and lack of gram-negative postoperative prophylactic coverage are modifiable risk factors for surgical site infection development. © 2016 Wiley Periodicals, Inc. Head Neck 38: First-1454, 2016.

Isavuconazole Treatment of Cryptococcosis and Dimorphic Mycoses.

BACKGROUND: Invasive fungal diseases (IFD) caused by Cryptococcus and dimorphic fungi are associated with significant morbidity and mortality. Isavuconazole (ISAV) is a novel, broad-spectrum, triazole antifungal agent (IV and by mouth [PO]) developed for the treatment of IFD. It displays potent activity in vitro against these pathogens and in this report we examine outcomes of patients with cryptococcosis or dimorphic fungal infections treated with ISAV. METHODS: The VITAL study was an open-label nonrandomized phase 3 trial conducted to evaluate the efficacy and safety of ISAV treatment in management of rare IFD. Patients received ISAV 200 mg 3 times daily for 2 days followed by 200 mg once-daily (IV or PO). Proven IFD and overall response at end of treatment (EOT) were determined by an independent, data-review committee. Mortality and safety were also assessed. RESULTS: Thirty-eight patients received ISAV for IFD caused by Cryptococcus spp. (n = 9), Paracoccidioides spp. (n = 10), Coccidioides spp. (n = 9), Histoplasma spp. (n = 7) and Blastomyces spp. (n = 3). The median length of therapy was 180 days (range 2-331 days). At EOT 24/38 (63%) patients exhibited a successful overall response. Furthermore, 8 of 38 (21%) had stable IFD at the end of therapy without progression of disease, and 6 (16%) patients had progressive IFD despite this antifungal therapy. Thirty-three (87%) patients experienced adverse events. CONCLUSIONS: ISAV was well tolerated and demonstrated clinical activity against these endemic fungi with a safety profile similar to that observed in larger studies, validating its broad-spectrum in vitro activity and suggesting it may be a valuable alternative to currently available agents. CLINICAL TRIALS REGISTRATION: NCT00634049.

Development and antimicrobial susceptibility studies of in vitro monomicrobial and polymicrobial biofilm models with Aspergillus fumigatus and Pseudomonas aeruginosa.

BACKGROUND: Mixed microbial infections of the respiratory tracts with P. aeruginosa and A. fumigatus capable of producing biofilms are commonly found in cystic fibrosis patients. The primary objective of this study was to develop an in vitro model for P. aeruginosa and A. fumigatus polymicrobial biofilm to study the efficacy of various antimicrobial drugs alone and in combinations against biofilm-embedded cells. Simultaneous static cocultures of P. aeruginosa and sporelings were used for the development of in vitro P. aeruginosa-A. fumigatus polymicrobial biofilm in SD broth in 24-well cell culture plates at 35°C, and the biofilm formation was monitored microscopically and spectrophotometrically. Using P. aeruginosa-A. fumigatus sporelings cocultures we examined the effects of various antimicrobial drugs alone and in combination against polymicrobial biofilm by CFU and tetrazolium reduction assays. RESULTS: In simultaneous static cocultures P. aeruginosa cells killed A. fumigatus conidia, whereas the bacterial cells showed no substantial fungicidal effect on sporelings grown for 12 h or longer at 35°C. Monospecies cultures of P. aeruginosa produced loosely adhered monomicrobial biofilm and addition of 10% bovine serum to the growth medium inhibited the formation of monomicrobial biofilm by P. aeruginosa whereas it produced tightly adhered polymicrobial biofilm in the presence of A. fumigatus mycelial growth. A. fumigatus produced firmly adherent monomicrobial and polymicrobial biofilms. A comparison of CFU and MTT assays showed that the latter is unsuitable for studying the effectiveness of antimicrobial treatment against polymicrobial biofilm. Tobramycin alone and in combination with posaconazole was highly effective against monomicrobial and polymicrobial biofilms of P. aeruginosa whereas cefepime alone and in combination with posaconazole showed excellent activity against monomicrobial biofilm of P. aeruginosa but was less effective against polymicrobial biofilm. Monomicrobial and polymicrobial biofilms of A. fumigatus showed similar susceptibility to posaconazole with and without the antibacterial drug. CONCLUSIONS: Simultaneous static coculture of A. fumigatus sporelings grown for 12 h or longer was superior to ungerminated conidia with P. aeruginosa for the development of A. fumigatus-P. aeruginosa biofilm. P. aeruginosa-A. fumigatus polymicrobial biofilm shows differential susceptibility to antimicrobial drugs whereas the susceptibility of A. fumigatus to antimicrobial drugs was unchanged.

Toxicity of spill-treating agents and oil to sea urchin embryos.

The aim of this study was to assess the joint toxicity of a Maya crude oil and four spill-treating agents (STAs) (CytoSol, Finasol OSR51, Agma OSD569 and OD4000). The acute toxicity of the binary mixtures of the water accommodated fractions (WAFs) obtained independently for the oil and each STA was assessed. The toxicity of the chemically enhanced WAF (CEWAF) of oil and Finasol OSR51 at several dispersant to oil ratios (1:2, 1:10 and 1:100) was also evaluated. The toxicity (EC50) obtained for the WAFs of the STAs was: CytoSol (15.1 mL/L)

Toxicity of binary mixtures of oil fractions to sea urchin embryos.

The assumption of additive toxicity for oil compounds is related to a narcotic mode of action. However, the joint toxicity of oil fractions has not been fully investigated. A fractionation of Maya crude oil into aliphatics, aromatics and polars was performed, fractions were dissolved in dimethyl sulfoxide (DMSO) and subsequently toxicity of single fractions and binary mixtures was assessed using the sea urchin embryo test. The descriptive ability of Concentration Addition (CA), Independent Action (IA) and modifications of both models for describing the joint toxicity of mixtures has also been evaluated. The hydrocarbon content extractable with dichloromethane of the fractions dissolved in DMSO was: 12.0 ± 1.8 mg mL(-1), 39.0 ± 0.5 mg mL(-1) and 20.5 ± 2.5 mg mL(-1) for aliphatics, aromatics and polars, respectively. The toxicity of the extracts in DMSO of the fractions as EC50 (µLL(-1)) was: aliphatics (165.8-242.3)

Effect of early metoprolol on infarct size in ST-segment-elevation myocardial infarction patients undergoing primary percutaneous coronary intervention: the Effect of Metoprolol in Cardioprotection During an Acute Myocardial Infarction (METOCARD-CNIC) trial.

BACKGROUND: The effect of ß-blockers on infarct size when used in conjunction with primary percutaneous coronary intervention is unknown. We hypothesize that metoprolol reduces infarct size when administered early (intravenously before reperfusion). METHODS AND RESULTS: Patients with Killip class II or less anterior ST-segment-elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention within 6 hours of symptoms onset were randomized to receive intravenous metoprolol (n=131) or not (control, n=139) before reperfusion. All patients without contraindications received oral metoprolol within 24 hours. The predefined primary end point was infarct size on magnetic resonance imaging performed 5 to 7 days after STEMI. Magnetic resonance imaging was performed in 220 patients (81%). Mean ± SD infarct size by magnetic resonance imaging was smaller after intravenous metoprolol compared with control (25.6 ± 15.3 versus 32.0 ± 22.2 g; adjusted difference, -6.52; 95% confidence interval, -11.39 to -1.78; P=0.012). In patients with pre-percutaneous coronary intervention Thrombolysis in Myocardial Infarction grade 0 to 1 flow, the adjusted treatment difference in infarct size was -8.13 (95% confidence interval, -13.10 to -3.16; P=0.0024). Infarct size estimated by peak and area under the curve creatine kinase release was measured in all study populations and was significantly reduced by intravenous metoprolol. Left ventricular ejection fraction was higher in the intravenous metoprolol group (adjusted difference, 2.67%; 95% confidence interval, 0.09-5.21; P=0.045). The composite of death, malignant ventricular arrhythmia, cardiogenic shock, atrioventricular block, and reinfarction at 24 hours in the intravenous metoprolol and control groups was 7.1% and 12.3%, respectively (P=0.21). CONCLUSIONS: In patients with anterior Killip class II or less ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention, early intravenous metoprolol before reperfusion reduced infarct size and increased left ventricular ejection fraction with no excess of adverse events during the first 24 hours after STEMI. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01311700. EUDRACT number: 2010-019939-35.

Inhibition kinetics of lipid oxidation of model foods by using antioxidant extract of fermented soybeans.

Fermentation by using Aspergillus oryzae has been reported to increase antioxidant activity of soybeans significantly. The effectiveness of the extract from fermented soybeans was studied in 3 model foods with different complexities, i.e., linoleic acid emulsion, sunflower oil emulsions and bulk sunflower oil. For the emulsion systems, oxidation at two different pH values (4.5 and 7) was also compared. A reparameterised logistic equation was used to describe and to predict the experimental data. In general, a good agreement between experimental trends and simulated data from the model was found. A crude antioxidant extract (5 mg/g) showed a comparable antioxidant activity to 0.26 mg/g of butylated hydroxytoluene (BHT) in the linoleic acid emulsions. The extract exhibited a better capability to retard primary products in the linoleic acid systems than the secondary products. The opposite effect was observed in the bulk sunflower oil and its emulsion systems.