Evaluating the Efficacy of Eravacycline and Omadacycline against Extensively Drug-Resistant Acinetobacter baumannii Patient Isolates.

For decades, the spread of multidrug-resistant (MDR) Acinetobacter baumannii has been rampant in critically ill, hospitalized patients. Traditional antibiotic therapies against this pathogen have been failing, leading to rising concerns over management options for patients. Two new antibiotics, eravacycline and omadacycline, were introduced to the market and have shown promising results in the treatment of Gram-negative infections. Since these drugs are newly available, there is limited in vitro data about their effectiveness against MDR A. baumannii or even susceptible strains. Here, we examined the effectiveness of 22 standard-of-care antibiotics, eravacycline, and omadacycline against susceptible and extensively drug-resistant (XDR) A. baumannii patient isolates from Cooper University Hospital. Furthermore, we examined selected combinations of eravacycline or omadacycline with other antibiotics against an XDR strain. We demonstrated that this collection of strains is largely resistant to monotherapies of carbapenems, fluoroquinolones, folate pathway antagonists, cephalosporins, and most tetracyclines. While clinical breakpoint data are not available for eravacycline or omadacycline, based on minimum inhibitory concentrations, eravacycline was highly effective against these strains. The aminoglycoside amikacin alone and in combination with eravacycline or omadacycline yielded the most promising results. Our comprehensive characterization offers direction in the treatment of this deadly infection in hospitalized patients.

Cranial helminths of Mustela vison Schreber, 1777 in Spain.

A survey was carried out to investigate the presence of cranial helminths in 337 American minks (Mustela vison) from Spain. This information was obtained partly in order to evaluate potential conservation problems and sanitary risks to the congeneric European mink (Mustela lutreola), one of the most endangered carnivores in the world. Skulls and rectal faeces of each specimen were simultaneously analysed. Troglotrema acutum and Skrjabingylus nasicola were found in 5.6% of the M. vison analysed. No cranial lesions were seen in any of the examined skulls. The finding of both helminths in Spanish free-living M. vison specimens enlarges their natural definitive host spectrum in Western Europe. One relatively important focus of T. acutum in M. vison was detected (30.4%) in the Spanish Alava province while S. nasicola was found to be very infrequent. The suitability of both analytical methods was assessed in order to know to what degree coprological analysis reflects the real prevalence of cranial helminths in this host. It is possible to conclude that coprological analysis can be used instead of necropsies to analyse the possible incidence of pathogenic cranial helminths in mustelids. This aspect is very important and useful when trying to analyse the helminthological status of endangered species such as the native mink (M. lutreola) particularly in areas where both congeneric species are present and strict competition occurs.

Bcl-xL promotes metastasis of breast cancer cells by induction of cytokines resistance.

Metastasis is a highly complex process involving the survival of tumor cells, both in the blood stream and within specific organs. Cell-death and survival are determined by a number of gene products from an expanding family of the Bcl-2 gene, either promoting or preventing apoptosis. Furthermore, the survival of tumor cells may favor the accumulation of additional genetic alterations causing further growth and invasive opportunities which may lead to metastasis. To examine whether the prevention of cell-death influences the metastatic behavior, we transfected a human breast cancer cell line MDA-MB-435 with the Bcl-xL cDNA and then studied metastatic ability of the selected clones in vivo. Our results show that Bcl-xL-clones had a decreased tumor growth latency and an increased metastatic ability. Apoptosis-resistance to cytokines was induced in 435 cells by Bcl-xL-expression with minor modifications in their proliferation rates. These cells also showed diminished adhesion to extracellular matrix proteins and a survival advantage in suspension over 435/Neo cells. Moreover, to determine survival in blood stream and in cells lodged in the lungs, we injected 435/Bcl-xL and 435/Neo cells at 1:3 proportion i.v., and animals were killed at intervals of 15' to 16 h after injection. Tumor cells were recovered from the lungs and Southern-blot analysis revealed the presence of exogenous Bcl-xL cDNA. These results showed that 435/Bcl-xL cells had a survival advantage in circulation over 435/Neo cells. This advantage in vivo was attributable to Bcl-xL expression. We conclude that Bcl-xL expression in breast cancer cells can increase metastatic activity. This advantage could be created by inducing resistance to apoptosis against cytokines, increasing cell survival in circulation, and enhancing anchorage-independent growth.

Brain maturation estimation using neural classifier.

Quantitative electroencephalographic (EEG) signal analysis has revealed itself as an important diagnostic tool in the last few years. Through the use of signal processing techniques, new quantitative representations of EEG data are obtained. To automate the diagnosis, a problem of supervised classification must be solved on these. Artificial Neural Networks provide an alternative to more traditional classifier systems for this task. The objective of this paper is to perform a comparison between several classifiers in a particular problem, the brain maturation prediction. The data preprocessing/feature extraction process and the methodology for making the comparison are described. Performance of the methods is evaluated in terms of estimated percentage of correctly classified subjects.

Red foxes (Vulpes vulpes) are a natural intermediate host of Neospora caninum.

The present study was undertaken to determine if red foxes are natural intermediate and/or definitive host for Neospora caninum and to study the importance of infection of N. caninum in this species in North-eastern Spain. Faecal samples and brain tissues were obtained from 122 foxes from 21 rural areas of Catalonia. Faeces collected were examined for parasite eggs and coccidian oocysts using sucrose flotation. For PCR-based diagnosis of N. caninum in brain tissues, the specific genomic Nc5 region was selected as the target sequence for DNA amplification. To control for PCR failure and facilitate identification of truly negative samples, the competitor pNc5C molecule was added to all negative samples in a second round of PCR reactions. Of the 122 foxes analysed, 13 (10.7%) were positive by PCR for N. caninum. Signal intensities of all positive samples were relatively weak with the exception of one sample from a 3-month male animal, that also showed the highest repeatability. No differences were observed by sex, age or area of sampling analysis. Detection of stages of N. caninum in brain from naturally infected red foxes demonstrated that red foxes are a natural intermediate host for N. caninum. Faecal samples were analysed for the presence of N. caninum oocysts, however, no oocysts compatible with N. caninum were found. A widespread latent infection of red foxes in North-eastern Spain found in the present study indicates that red foxes could have a very important role in the epidemiology of neosporosis in our area.

Aleutian mink disease parvovirus in wild riparian carnivores in Spain.

Serious declines in populations of native European mink (Mustela lutreola) have occurred in Europe. One responsible factor may be infectious diseases introduced by exotic American mink (Mustela vison). In order to investigate a possible role for Aleutian mink disease parvovirus (ADV), we surveyed native riparian carnivores and feral American mink. When serum samples from 12 free-ranging European and 16 feral American mink were tested, antibodies to ADV were detected from three of nine European mink. ADV DNA was detected by polymerase chain reaction in whole cell DNA from four of seven carcasses; two American mink, one European mink and a Eurasian otter (Lutra lutra). Lesions typical of Aleutian disease were present in one of the American mink. A portion of the ADV VP2 capsid gene was sequenced and the results suggested that two sequence types of ADV were circulating in Spain, and that the Spanish ADVs differed from other described isolates from North America and Europe. Future conservation and restoration efforts should include measures to avoid introduction or spread of ADV infection to native animals.

[The combined application of visual evoked potentials and the quantified electroencephalogram improve discrimination of cerebral maturity]. / La aplicación conjunta del potencial evocado visual y el electroencefalograma cuantificado mejora la discriminación de la maduración cerebral.

INTRODUCTION AND OBJECTIVE: The aim of this job is to evaluate brain maturation by means of Electroencephalogram (EEG) and Visual Evoked Potentials stimulated with flash (VEP-flash) quantitative analysis techniques. MATERIAL AND METHODS: The transversal study is made on a sample of 96 subjects in which EEG and VEP-flash, first isolated and then joining both, are analyzed. The selection of spectral parameters was done taking care of all the subjects were selected in the sense of maximizing brain maturation discrimination. Multivariate analysis techniques for classifying subjects were used. EEG and VEP-flash variables were selected with the linear discriminant analysis. In the EEG case the variables take into account, as a reference, either the median of the power spectrum or either the time instant in which the spectral power in every band reaches its maximum value. In the joined EEG-VEP-flash the VEP variables which give more information were related with the slopes and distances between the basic peaks of the evoked response (N1, P1 and N2) and age. For brain maturation evaluation the variables in the occipital channels are sufficient, being those of the right hemisphere the most diagnostic significative ones. CONCLUSION: The joined use of EEG and VEP-flash means an improvement in the maturative level discrimination regarding to the isolated consideration of any of them. Variables obtained from the EEG-VEP-flash are enough for brain maturation evaluation.

[A study of cerebral maturity by means of quantitative analysis of the electroencephalogram]. / Estudio de la maduración cerebral mediante el análisis cuantitativo del electroencefalograma.

INTRODUCTION AND OBJECTIVE: The objective of this study is to evaluate cerebral maturity by means of quantitative analysis techniques applied to the electroencephalogram (EEG). MATERIAL AND METHODS: A transversal study of cerebral maturity was carried out in 403 persons who had undergone an EEG. A previous pilot study had been carried out of 103 persons. A series of spectral parameters of the EEG were selected so that all those studied were in the most similar conditions possible. Different frequency bands were analyzed choosing the one with best discrimination of the maturity aspect. Classification of the different levels of cerebral maturity was done with the help of multivariant analysis. The value of the median of the frequencies and the spectrum of relative potencies at the moment when a frequency band is at a maximum are the parameters which evolve best with age and best discriminate maturity Spectral analysis allows selection of the frequency bands most suitable to the problem. Working with two frequency bands is sufficient to evaluate cerebral maturity. RESULTS: The variables obtained in the occipital channels were sufficient for evaluation of cerebral maturity. Those of the right hemisphere were more significant for diagnosis. The occipital channels are the most relevant in the study of cerebral maturity. CONCLUSIONS: The neuronal network is the most efficient classifier for classification of different groups of maturity The next most efficient method is by quadratic discriminant analysis. Consideration of the variables, taking into account the factors of stability and regularity of the EEG signals improves discrimination with respect to the average of those recorded during the entire procedure.

[Neurinoma of the 8th nerve]. / Neurinoma del VIII par.

Before an acoustic neuroma case, with a buds evolution, coincident with influenza, actually the most significant explorations are revised, a protocol is proposed, and discussing the convenience to repeat specific explorations after a year when the first explorations have been iniciativelly negatives; being insinuated the possibility that some virus infections could act as a stimulus in the speed of neuromas growth.

Phosphinic platinum complexes with 8-thiotheophylline derivatives: synthesis, characterization, and antiproliferative activity.

The platinum mixed-phosphine complexes (SP-4,2)-[PtCl(8-MTT)(PPh3)(PTA)] (2) and cis-[Pt(8-MTT)2(PPh3)(PTA)] (3) (MTTH2 = 8-(methylthio)theophylline, PTA = 1,3,5-triaza-7-phosphaadamantane) have been prepared from the precursor cis-[PtCl2(PPh3)(PTA)] (1), which has been fully characterized by X-ray diffraction determination. Antiproliferative activity tests indicated that the presence of one lipophilic PPh3 and one hydrophilic PTA makes 1-3 more active than the analogues bearing two PPh3 or two PTA. The reactivity of cis-[PtCl2(PPh3)2], cis-[PtCl2(PTA)2], and cis-[PtCl2(PPh3)(PTA)] with the bis(thiopurines) bis(S-8-thiotheophylline)methane (MBTTH2), 1,2-bis(S-8-thiotheophylline)ethane (EBTTH2), and 1,3-bis(S-8-thiotheophylline)propane (PBTTH2) has also been investigated. New binuclear complexes have been prepared and identified by spectroscopic techniques and their antiproliferative activities on T2 and SKOV3 cell lines evaluated.

Expression of death-related genes and their relationship to loss of apoptosis in T1 ductal breast carcinomas.

Expression of the death-related proteins (DRPs) Bcl-2, Bax, Bcl-x and Bak that regulate cell survival and death was examined using immuno-histochemical methods in a group of 142 T1 (<2 cm) ductal breast carcinomas. Immunostaining results were correlated with loss of apoptosis and clinicopathological parameters such as histological grade (HG) and lymph node involvement. Expression of anti-apoptotic proteins Bcl-2 and Bcl-x was found in 57.0% and 62.75% of tumors, respectively. Bcl-2 expression, but not Bcl-x expression, was related to loss of apoptosis. Expression of the apoptotic proteins Bax and Bak was present in 58% of Bcl-2-negative tumors and associated significantly with an increase in apoptosis. Expression of these DRPs was associated significantly with the HG of the tumors: Bcl-2 and Bak expression was predominant in HG I/II tumors, whereas expression of Bcl-xL and Bax was commonly observed in HG III tumors, as occurs for p53 over-expression. Our results suggest that the loss or gain of apoptosis is regulated tightly in T1 breast carcinomas through the expression of different effectors along with tumor cell differentiation.

Microsatellite instability is associated with the loss of apoptosis in ductal breast carcinomas.

Metastatic progression in ductal breast carcinomas are related to apoptosis in primary tumors. Frameshift mutations in a single-repeat sequence within the coding region (G)8 of the pro-apoptotic Bax gene have been related to microsatellite instability (MSI) and progression of some carcinomas and lymphomas. The aim of this study was to explore whether the extended lifespan of breast cancer cells can also be triggered by Bax mutation in ductal-breast carcinomas, and whether breast cancer cell MSI is related to the loss of apoptosis. For this purpose we studied frameshift mutations of a microsatellite (G)8 in the third exon of the Bax gene in a series of 105 ductal breast carcinomas, at T1 and T2-3 stages, 45 of which had lymph node metastasis. We analyzed MSI in five sequences of DNA isolated from normal and tumor tissue samples taken from 86 patients, and we explored the relationship between MSI and tumor apoptosis status. Bax mutation was not present in ductal breast carcinomas. MSI (two or more markers altered) was detected in 11.6% of tumors. Loss of apoptosis occurred in 80% (8/10) tumors with MSI, versus 17.8% of tumors without MSI (chi2 test, p = 0.0004), independently of Bax protein expression. We conclude that frameshift mutations of a microsatellite (G)8 of the Bax gene are not critical for the loss of apoptosis in breast cancer, and that loss of apoptosis may be a consequence of overexpression of anti-apoptotic protein Bcl-2 or Bcl-xL. Moreover, MSI in breast carcinomas might be the cause of loss of an apoptotic pathway that is not induced by frameshift mutations of a microsatellite (G)8 of the Bax gene.

Biologically active platinum complexes containing 8-thiotheophylline and 8-(methylthio)theophylline.

Complexes [Pt(mu-N,S-8-TT)(PPh(3))(2)](2) (1), [Pt(mu-S,N-8-TT)(PTA)(2)](2) (2), [Pt(8-TTH)(terpy)]BF(4) (3), cis-[PtCl(8-MTT)(PPh(3))(2)] (4), cis-[Pt(8-MTT)(2)(PPh(3))(2)] (5), cis-[Pt(8-MTT)(8-TTH)(PPh(3))(2)] (6), cis-[PtCl(8-MTT)(PTA)(2)] (7), cis-[Pt(8-MTT)(2)(PTA)(2)] (8), and trans-[Pt(8-MTT)(2)(py)(2)] (9) (8-TTH(2) = 8-thiotheophylline; 8-MTTH = 8-(methylthio)theophylline; PTA = 1,3,5-triaza-7-phosphaadamantane) are presented and studied by IR and multinuclear ((1)H, (31)P[(1)H]) NMR spectroscopy. The solid-state structure of 4 and 9 has been authenticated by X-ray crystallography. Growth inhibition of the cancer cells T2 and SKOV3 induced by the above new thiopurine platinum complexes has been investigated. The activity shown by complexes 4 and 9 was comparable with cisplatin on T2. Remarkably, 4 and 9 displayed also a valuable activity on cisplatin-resistant SKOV3 cancer cells.

Tools for acquisition, processing and knowledge-based diagnostic of the electroencephalogram and visual evoked potentials.

The objective of our research is to develop computer-based tools to automate the clinical evaluation of the electroencephalogram (EEG) and visual evoked potentials (VEP). This paper describes a set of solutions to support all the aspects regarding the standard procedures of the diagnosis in neurophysiology, including: (1) acquisition and real-time processing and compression of EEG and VEP signals, (2) real-time brain mapping of spectral powers, (3) classifier design, (4) automatic detection of morphologies through supervised neural networks. (5) signal analysis through fuzzy modelling, and (6) a knowledge based approach to classifier design.

Management of vasospasm in a neurosurgical center / Management of vasospasm in a neurosurgical center

Background: Cerebral vasospasm after subarachnoid hemorrhage remains a major source of morbidity and mortality. Various agents have come into vogue to deal with this complication but none has shown any absolute results. We conducted this study to asses the effectiveness of intracisternal lavage of papavarine both prophylactically and therapeutically in a simple cost effective way. Methods: This is a retrospective analysis of patients who were admitted at our institution between January 2002 and July 2003. Eighty five patients with anterior circulation aneurysmal bleed who underwent microsurgical clipping were divided into two groups. Group A: patients who received papavarine through a reservoir and Group B patients who did not receive papavarine. The location of aneurysm, timing of surgery , incidence and outcome of vasospasm were assessed in the patients in two comparable groups. Results: 13 por ciento of patients in Group A developed vasospasm whereas 38 por ciento of patients in Group B developed vasospasm. Symptoms of vasospasm reversed in all patients in Group A. There were 3 deaths in Group A but none where attributed to vasospasm. Four of seven deaths in Group B were attributed to consequence of vasospasm. Eleven patients who survived in Group B in spite of vasospasm had significant morbidity at the time of discharge. Conclusion: Intracisternal lavage with papavarine both prophylactically and theraputically can prevent and reverse vasospasm and this can be achieved by installing a simple reservoir. It is a cost effective and rapid bedside procedure for dealing with vasospasm