Synthesis, spectroscopic, chemical reactivity, topology analysis and molecular docking study of ethyl 5-hydroxy-2-thioxo-4-(p-tolyl)-6-(trifluoromethyl)hexahydropyrimidine-5-carboxylate.

The organofluorine hexahydropyrimidine derivatives are used in the drug discovery due to its steric nature to hydrogen and its extreme electronegativity. The Ethyl 5-hydroxy-2-thioxo-4-(p-tolyl)-6-(trifluoromethyl)hexahydropyrimidine-5-carboxylate (ETP5C) compound was synthesized and characterized by NMR (13C and 1H), FT-IR and UV-Vis spectroscopic techniques for experimentally and theoretically and elemental analyses, mass spectra also investigated. The most stable structure of synthesized molecule was studied by PES analysis in gas and liquid medium. The structural parameters such as bond length and bond angle of the title molecule have been obtained by DFT/B3LYP/6-311++G (d,p) set and compared with the structurally related experimental data of the compounds. The π-to-π* transition of the ETP5C molecule is identified using UV-Vis absorption spectral analysis. In addition, the chemical stability and reactivity are investigated using HOMO-LUMO analysis. The minimal HOMO-LUMO energy gap (4.6255 eV) clearly explains that the ETP5C molecule is more reactive for receptors. The nucleophilic and electrophilic regions such as active sites have been shown by MEP, ELF, LOL and Fukui functions. The second order optical effect has been explained by NLO analysis. The docking was performed with antineoplastic proteins that exhibit against the development of tumor cells.

Metaheuristic Optimization-Driven Novel Deep Learning Approach for Brain Tumor Segmentation.

Brain tumor has the foremost distinguished etiology of high morality. Neoplasm, a categorization of brain tumors, is very operative in distinguishing and determining the tumor's exact location in the brain. Magnetic resonance imaging (MRI) is an efficient noninvasive technique for the anatomical examination of brain tumors. Growth tissues have a distinguishable look in MRI pictures in order that they are unit-wide used for brain tumor feature extraction. The existing research algorithms for brain tumors have some limitations such as different qualities, low sensitivity, and diagnosing the tumor at its stages. In this particular piece of research, an innovative method of optimization known as the procedure for lightning attachment algorithm (PLA) is used, and for the purpose of classification, a CNN model known as DenseNet-169 is applied. PLA was used in order to optimize the growth, and a network model known as the DenseNet-169 model was utilized in order to extract the various growth-optimization choices. First, the MR images of the brain were preprocessed to remove any outliers. Next, the Dense Net-169 CNN model was used to extract network choices from the MR images. In addition, it is used to execute the function of a classifier in order to identify the growth as either an aberrant growth or a traditional growth. In addition, the publicly benchmarked datasets that are widely utilized have validated the algorithmic rule that was granted. The planned system demonstrates the satisfactory accuracy in getting ready to on the dataset and outperforms many of the notable current techniques.

Simultaneous Raman microspectroscopy and fluorescence imaging of bone mineralization in living zebrafish larvae.

Confocal Raman microspectroscopy and fluorescence imaging are two well-established methods providing functional insight into the extracellular matrix and into living cells and tissues, respectively, down to single molecule detection. In living tissues, however, cells and extracellular matrix coexist and interact. To acquire information on this cell-matrix interaction, we developed a technique for colocalized, correlative multispectral tissue analysis by implementing high-sensitivity, wide-field fluorescence imaging on a confocal Raman microscope. As a proof of principle, we study early stages of bone formation in the zebrafish (Danio rerio) larvae because the zebrafish has emerged as a model organism to study vertebrate development. The newly formed bones were stained using a calcium fluorescent marker and the maturation process was imaged and chemically characterized in vivo. Results obtained from early stages of mineral deposition in the zebrafish fin bone unequivocally show the presence of hydrogen phosphate containing mineral phases in addition to the carbonated apatite mineral. The approach developed here opens significant opportunities in molecular imaging of metabolic activities, intracellular sensing, and trafficking as well as in vivo exploration of cell-tissue interfaces under (patho-)physiological conditions.

[Hyper- or normobaric oxygen therapy to treat migraine and cluster headache pain. Cochrane review]. / Hyper- bzw. normobare Sauerstofftherapie zur Behandlung von Migräne und Clusterkopfschmerzen. Cochrane Review.

BACKGROUND: The aim of this systematic review was to assess the benefits and harms of supplemental oxygen (HBOT/NBOT) for treating and preventing migraine and cluster headaches. MATERIAL AND METHODS: All randomized trials comparing the effect of supplemental oxygen on migraine or cluster headache with those that exclude supplemental oxygen were included in this review. The systematic search included all relevant sources according to the paradigms of the Cochrane Collaboration. Data were analyzed with RevMan 4.2. RESULTS: Nine trials involving 201 participants satisfied the inclusion criteria. HBOT was effective in relieving an acute migraine and seemed to be sufficient in the treatment of an acute cluster attack. NBOT was effective in terminating acute cluster headache compared to sham treatment, but not in comparison to sublingual ergotamine. There was no evidence for any prophylactic effects. Serious adverse effects were not noted in the trials investigated. CONCLUSIONS: There is some evidence that HBOT is effective for termination of acute migraine. NBOT was similarly effective in cluster headache, however with sparse data. Because of costs and poor availability HBOT cannot be regarded as a routine therapy. Further indications in the case of treatment failure using standard therapy need to be defined based on data of future clinical trials.

Causes and timing of death in patients with ARDS.

BACKGROUND: Since the early 1980s, case fatality of patients with ARDS has decreased, and explanations are unclear. DESIGN AND METHODS: Using identical definitions of ARDS and organ failure, we analyzed consecutive cohorts of patients meeting syndrome criteria at our institution in 1982 (n = 46), 1990 (n = 112), 1994 (n = 99), and 1998 (n = 205) to determine causes and timing of death. RESULTS: Overall case fatality has decreased from 68% in 1981-1982 to a low of 29% in 1996, plateauing since the mid-1990s (p = 0.001 for trend). Sepsis syndrome with multiple organ failure remains the most common cause of death (30 to 50%), while respiratory failure causes a small percentage (13 to 19%) of deaths. The distribution of causes of death has not changed over time. There was no change in the timing of death during the study periods: 26 to 44% of deaths occurred early (< 72 h after ARDS onset), and 56 to 74% occurred late (> 72 h after ARDS onset). However, the increased survival over the past 2 decades is entirely accounted for by patients who present with trauma and other risk factors for their ARDS, while survival for those patients whose risk factor is sepsis has not changed. Additionally, withdrawal of life support in these patients is now occurring at our institution significantly more frequently than in the past, and median time until death has decreased in patients who have support withdrawn. CONCLUSIONS: While these results do not explain the overall case fatality decline in ARDS, they do indicate that sepsis syndrome remains the leading cause of death and suggest that future therapies to improve survival be targeted at reducing the complications of sepsis.

Micronutrient concentrations in patients with malignant disease: effect of the inflammatory response.

BACKGROUND: Micronutrient deficiencies may occur in patients with malignancy due to a variety of possible causes, including unbalanced dietary intake and adverse effects of treatment. In addition, many patients show signs of a chronic inflammatory response, which can affect circulating concentrations of certain vitamins and trace elements. Our aim was to examine the effect of the inflammatory response, as determined by plasma C-reactive protein (CRP) concentrations, on a range of micronutrients in patients with malignancy. METHODS: Blood samples were collected from 50 patients with various malignancies for the measurement of vitamins A, E, C and B(1), the trace elements copper, zinc, selenium and manganese and the inflammatory marker CRP. Vitamin A was measured as retinol and vitamin E as alpha-tocopherol. Vitamin C measurement included both ascorbic acid and dehydroascorbic acid. The vitamins were assayed by high-performance liquid chromatography and the trace elements by atomic-absorption spectroscopy. RESULTS: Concentrations of zinc and selenium below their respective reference ranges and copper and manganese above their respective reference ranges were commonly found in the cancer group. However, none of these elements showed any significant correlation with CRP (P >0.01). Reduced levels of vitamin A, C and B(1) were commonly found in the cancer group. Vitamins A and C showed a significant negative correlation with CRP (r(s)=-0.66, P <0.0001 and r(s)=-0.53, P = 0.0005, respectively). Vitamin E showed no correlation with CRP. CONCLUSION: The inflammatory response is a major consideration in the interpretation of vitamin A and C concentrations in patients with malignancy.

Neuronal cell death, nerve growth factor and neurotrophic models: 50 years on.

Viktor Hamburger has just died at the age of 100. It is 50 years since he and Rita Levi-Montalcini laid the foundations for the study of naturally occurring cell death and of neurotrophic factors in the nervous system. In a period of less than 10 years, from 1949 to 1958, Hamburger and Levi-Montalcini made the following seminal discoveries: that neuron cell death occurs in dorsal root ganglia, sympathetic ganglia and the cervical column of motoneurons; that the predictions arising from this observation, namely that survival is dependent on the supply of a trophic factor, could be substantiated by studying the effects of a sarcoma on the proliferation of ganglionic processes both in vivo and in vitro; and that the proliferation of these processes could be used as an assay system to isolate the factor. This work provides a short review mostly of the early history of this subject in the context of the Hamburger/Levi-Montalcini paradigm. This acts as an introduction to a consideration of models that have been proposed to account for how the different sources of growth factors provide for the survival of neurons during development. It is suggested that what has been called the 'social-control' model provides the most parsimonious quantitative description of the contribution of trophic factors to neuronal survival, a concept for which we are in debt to Viktor Hamburger and Rita Levi-Montalcini.

Host specificity of Trypanosoma (Herpetosoma) species: evidence that bank voles (Clethrionomys glareolus) carry only one T. (H.) evotomys 18S rRNA genotype but wood mice (Apodemus sylvaticus) carry at least two polyphyletic parasites.

The strongest evidence for host specificity of mammalian trypanosomes comes from parasites of the subgenus Trypanosoma (Herpetosoma). Laboratory studies have shown that T. (Herpetosoma) species will not infect an alternative host. However, this has not been demonstrated in wild populations. We screened 560 bank voles (Clethrionomys glareolus) and 148 wood mice (Apodemus sylvaticus) for trypanosomes by PCR amplification of the 18S rRNA gene. In total, 109 (19%) bank voles and 12 (8%) wood mice were infected. A HaeIII restriction site was discovered that could be used to discriminate between T. (H.) evotomys of the bank vole and T. (H.) grosi of the wood mouse. All the parasites in the bank voles were identified as T. (Herpetosoma) evotomys by RFLP-PCR. Out of the 12 wood mouse infections 10 were due to T. grosi. Two of the wood mice were infected with parasites with a novel genotype that was most similar to those of T. evotomys and T. microti of voles. Fifty-six fleas collected from the rodents were also screened for trypanosomes; 9 were infected with T. evotomys and 1 with T. grosi. One of the fleas infected with T. evotomys was collected from a wood mouse.

Variation in quantal secretion at different release sites along developing and mature motor terminal branches.

The secretion of a quantum by groups of release sites (me) along the length of nerve terminal branches has been studied with extracellular electrodes at mature and juvenile toad neuromuscular junctions. The position of the recording sites with respect to the terminal branches was determined following zinc-iodide staining of terminals. me declined with distance from the last myelin segment along individual terminal branches: in a [Ca]o of 0.35 mM, me declined by 80% over a distance of 60 micron along mature terminal branches. Simultaneous recording of secretion from adjacent groups of release sites with two extracellular electrodes confirmed that secretion of a quantum at release sites declines with the distance of the sites from the last myelin segment. The secretion of a quantum by groups of release sites along juvenile terminal branches also declines with distance from the last myelin segment: me is always largest for the first release sites to be laid down. The facilitated secretion of quanta at sites with low me is larger than those with high me; as a consequence, all sites secrete similar numbers of quanta at the end of a short high-frequency train.

Homograft replacement of aortic valve and ascending aorta in a patient with non-specific giant cell aortitis.

A case of giant cell aortitis causing ascending aortic aneurysm associated with aortic regurgitation is reported. The aneurysm was excised and the aortic valve replaced using a fresh homograft. The patient has been followed up for three and a half years. There is good evidence of correction of the haemodynamic lesion and no evidence of further arteritis or aneurysmal formation. The pathological and clinical problem of this disease are discussed.