The Future of Neurocritical Care Research: Proceedings and Recommendations from the Fifth Neurocritical Care Research Network Conference.

The Fifth Neurocritical Care Research Network (NCRN) Conference held in Boca Raton, Florida, in September of 2018 was devoted to challenging the current status quo and examining the role of the Neurocritical Care Society (NCS) in driving the science and research of neurocritical care. The aim of this in-person meeting was to set the agenda for the NCS's Neurocritical Care Research Central, which is the overall research arm of the society. Prior to the meeting, all 103 participants received educational content (book and seminar) on the 'Blue Ocean Strategy®,' a concept from the business world which aims to identify undiscovered and uncontested market space, and to brainstorm innovative ideas and methods with which to address current challenges in neurocritical care research. Three five-member working groups met at least four times by teleconference prior to the in-person meeting to prepare answers to a set of questions using the Blue Ocean Strategy concept as a platform. At the Fifth NCRN Conference, these groups presented to a five-member jury and all attendees for open discussion. The jury then developed a set of recommendations for NCS to consider in order to move neurocritical care research forward. We have summarized the topics discussed at the conference and put forward recommendations for the future direction of the NCRN and neurocritical care research in general.

Effect of human albumin on TCD vasospasm, DCI, and cerebral infarction in subarachnoid hemorrhage: the ALISAH study.

BACKGROUND AND PURPOSE: The neuroprotective effects of human albumin have been studied in animal models of stroke and in humans with various intracranial disorders. We investigated the effect of 25 % human albumin (ALB) on mean cerebral blood flow velocities (MCBFV), delayed cerebral ischemia (DCI), and cerebral infarction. METHODS: We studied patients from the Albumin in Subarachnoid Hemorrhage (ALISAH) pilot clinical trial. We collected data on MCBFV as measured by transcranial Doppler ultrasound (TCD), incidence of DCI, and cerebral infarctions on head computed tomography (CT) scan at 90 days. RESULTS: TCD showed vasospasm in 75 % (n = 15), 55 % (n = 11), and 29 % (n = 2) of subjects in dosage tiers 1, 2, and 3, respectively. DCI was present in 20 % (n = 4), 15 % (n = 3), and 14 % (n = 1) of subjects in dosage tiers 1, 2, and 3, respectively. Cerebral infarctions were seen in 45 % (5 of 9), 27 % (3 of 18), and 25 % (1 of 4) of subjects who had follow-up head CT scans in dosage tiers 1, 2, and 3, respectively. CONCLUSIONS: Higher dosages of ALB were associated with a lower incidence of TCD vasospasm, DCI, and cerebral infarction at 90 days in a dose-dependent manner.

Circulus arteriosus cerebri: a study of variation in the fetal and adult human brains of south Indians.

The Circle of Willis or Circulus Arteriosus Cerebri and its branches are subject to many variations. The Circle of Willis with a classical description is very rare. The constituent arteries forming the circle vary greatly in size in different individuals and on two sides in the same subject. Study by dissection or by angiographic methods by several workers has shown that deviations from the normal pattern occur in a very high proportion of cases. There are differing views regarding the variations in the circle. Thus, this study was done to compare our findings with the others. In the present study, each artery taking part in the circle has been described in relation to the length, size and its origin separately and the findings have been compared.

p53 expression in oral cancer: observations of a South Indian study.

Oral cancers constitute a significant proportion of hospital admissions among cancer patients in India. The aim of this study was to elucidate the role of tumour suppressor gene p53 in the pathogenesis of oral squamous cell carcinoma by immunohistochemistry. Though extensive studies on p53 alterations in oral cancers have been done in Western countries and some Asian countries, only a few studies have emerged from India, especially the Southern states. This study would therefore be helpful in providing an Indian perspective, with particular reference to South Indian states. A total of 110 cases of oral squamous cell carcinoma, 35 dysplastic lesions, 15 hyperplastic lesions, and 50 samples of normal mucosa were assessed for p53 expression. Out of 110 cases of oral carcinoma, 40 (36%) were p53 positive. Among 35 cases of dysplastic lesions studied, 6 (17%) showed p53 positive staining. None of the hyperplastic lesions and normal oral lesions showed any evidence of p53 positivity. However, in 9 out of 40 (23%) cases of positive infiltrating squamous cell carcinomas, the adjacent or overlying non-tumourous epithelium demonstrated focal areas of p53 positive staining in the basal and parabasal layers of the epithelium. In addition, in 7 out of 110 (6%) cases, cytoplasmic staining was observed. In these samples, nuclei were not stained. Our results indicate that p53 over-expression may be involved in only a certain proportion of oral carcinomas. The fact that 6% of the dysplastic lesions were p53 positive, and adjacent non-tumourous epithelium of 23% infiltrating squamous cell carcinomas showed positive staining for p53 in the progenitor compartment of the epithelium indicates that p53 immunoreactivity could be used to detect early tumours as well.

Synthesis, characterization and the first crystal structure of the Zn(II) complex of 4,6-O-ethylidine-N-(2-hydroxybenzylidene)-beta-D-glucopyranosylamine.

4,6-O-Ethylidine-N-(2-hydroxybenzylidene)-beta-D-glucopyranosylamine (H(3)L(1)) and N-(5-bromo-2-hydroxybenzylidene-4,6-O-ethylidine-beta-D-glucopyranosylamine (H(3)L(2)) molecules possessing a single bond C-1 single bond N double bond C(H) single bond moiety for metal-ion binding were synthesized by condensing the 4,6-O-ethylidene-beta-D-glucopyranosylamine with salicylaldehyde or 5-bromosalicylaldehyde. Complexes of these ligands with Zn(II) were isolated and characterized using elemental analysis, FTIR, UV-Vis absorption, NMR spectroscopic and FAB mass spectrometric techniques. The structure of the Zn(II) complex derived from H(3)L(1) was established for the first time by a single-crystal X-ray diffraction study. The anomeric nature of the saccharide moiety was established based on (1)H NMR studies and was confirmed by the crystal structure. Further, the structure and binding aspects of the ligand, and the coordination features of this in its Zn(II) complex were derived from the corresponding crystal structure.

Interaction of metal ions with N-glycosylamines: isolation and characterization of the products of 4,6-O-benzylidene-N-(o-carboxyphenyl)-beta-D-glucopyranosylamine with different metal ions.

Metal-ion complexes of Li(+), Na(+), K(+), Mg(2+), Ca(2+), Ba(2+), Pb(2+), Cd(2+), Hg(2+) with 4,6-O-benzylidene-N-(o-carboxyphenyl)-beta-D-glucopyranosylamine were synthesized and isolated as solid products and characterized by analytical means as well as by spectral techniques, such as, 1H and 13C NMR, FTIR, absorption, FAB mass spectrometry, optical rotation and CD. While the alkali metal ions formed ML type of complexes, the other metal ions formed ML(2) type complexes. Molecular weights of the complexes of Li(+), Na(+) and K(+) were established based on the molecular-ion peaks in the FAB mass spectra. The saccharide portion remains in the beta-anomeric form even after the complexation. The spectral data, as well as the trends observed in the chemical shifts, indicate the interaction preferences between this glycosyl amine and different metal ions, and further reveal certain structural features of the complexes.

Synthesis, characterisation and crystal structures of Schiff bases from the reaction of 4,6-O-ethylidene-beta-D-glucopyranosylamine with substituted salicylaldehydes.

Multiple chemical modifications were carried out on D-glucose to result in the corresponding Schiff bases. Such modifications performed on D-glucose not only helped in increasing the solubility of the products in nonaqueous solvents, but also restricted the anomerisation of the saccharide moiety in solution. NMR study of the products revealed the presence of the beta-anomeric form of the saccharide moiety in Me(2)SO solution. All the compounds were characterised by analytical and spectral methods. The literature is devoid of any crystal structures of saccharide-Schiff base combinations of the type reported in this paper. The crystal structures of these molecules exhibited a tridentate, ONO binding core. These studies further revealed that the compounds in the solid state were in the beta-D-pyranose form with the (4)C(1) chair conformation. The compounds exhibited interesting lattice structures assisted through weak interactions of the type O-H...O and C-H...O. The lattice structure of one of these compounds exhibited channels filled with chloroform molecules.

Synthesis and characterisation of N-glycosyl amines from the reaction between 4,6-O-benzylidene-D-glucopyranose and substituted aromatic amines and also between 2-(o-aminophenyl)benzimidazole and pentoses or hexoses.

Twelve N-glycosyl amines were synthesised using 4,6-O-benzylidene-D-glucopyranose and different substituted aromatic amines, including some diamines that resulted in bis-glycosyl amines. Another set of six N-glycosyl amines was synthesised using different hexoses and pentoses and 2-(o-aminophenyl)benzimidazole. All compounds were isolated as solid products and purified, their elemental compositions were established, and these were characterised by NMR (1H and 13C), UV-Vis, and FTIR spectroscopy, by FAB mass spectrometry (molecular-ion peaks gave molecular weights), and by their optical rotations. While the protected saccharide, 4,6-O-benzylidene-D-glucopyranose, exists as a mixture of beta and alpha anomers in solution, the corresponding N-glycosyl amines were of only the beta anomeric form as determined by NMR and FTIR spectroscopy. On the other hand, N-glycosyl amines synthesised from 2-(o-aminophenyl)benzimidazole prefer the alpha anomeric form, and in two cases a mixture of both the beta and the alpha anomers were observed. The trends observed in the chemical shifts were compared among different products.

Interaction of saccharides with rare earth metal ions: synthesis and characterisation of Pr(III)- and Nd(III)-saccharide complexes.

A number of complexes are synthesised with Pr(III) and Nd(III) employing the mono- and disaccharides, D-glucose, D-galactose, D-mannose, D-arabinose, D-ribose, D-xylose, maltose and lactose. The complexes are characterised by various spectral and analytical techniques, and based on these data, appropriate structures were assigned for all complexes.

Lanthanide-saccharide chemistry: synthesis and characterisation of Ce(III)-saccharide complexes.

A series of nine Ce(III) complexes has been synthesised with seven different monosaccharides (D-glucose, D-fructose, D-galactose, D-mannose, L-sorbose, D-ribose and D-xylose) and two different disaccharides (D-maltose and L-lactose), and these have been characterised with various analytical, spectral, magnetic and electrochemical techniques. The NMR studies have highlighted some interesting features about the metal-ion-binding pattern of the saccharides. Some additional coordination has been proposed along with the chelating groups in the saccharide molecules, based on the shifts in 13C NMR spectra. On the other hand, solution absorption studies and solid-state magnetic susceptibilities have indicated the contribution from the d-character to the spectral features to some extent.

Reducing agents mitigate protein synthesis inhibition mediated by vanadate and vanadyl compounds in reticulocyte lysates.

Recently, we synthesized and characterized vanadyl saccharides to evaluate the effects of various vanadate and vanadyl complexes, which differ in their oxidation states on various biomacromolecules and cellular activities (1, 2). Here, we report that both vanadate (+V oxidation state) and different vanadyl species (+IV oxidation state) such as vanadyl D-glucose, vanadyl diascorbate, and vanadyl sulfate, impair the formation of polysomes and inhibit the initiation of protein synthesis in hemin-supplemented rabbit reticulocyte lysates. Vanadate inhibits protein synthesis more severely than vanadyl species and is consistent with the idea that vanadate is reduced to vanadyl state intracellularly. The inhibition of protein synthesis caused by low concentrations (10-20 microM) of vanadate and vanadyl species is effectively mitigated by reducing agents such as dithiothreitol, reduced glutathione (GSH), or reduced pyridine dinucleotide. A significant decrease in the protein synthesis inhibition in vanadate-treated lysates by GSH suggests that the mechanism of protein synthesis inhibition by vanadate is different than the action of other oxidants such as heavy metal ions and oxidized glutathione. This suggestion is also consistent with the findings that vanadium compounds do not stimulate phosphorylation of the alpha (alpha) subunit of initiation factor 2 (eIF2) or decrease the guanine nucleotide exchange activity of eIF2B, which is required to exchange GDP for GTP in eIF2.GDP binary complex. The reduction of vanadate to vanadyl state and the subsequent complex formation of vanadyl species with the endogenous reducing compounds or with the -SH groups of certain proteins may be the cause for protein synthesis inhibition in lysates.

Transition-metal saccharide chemistry and biology: saccharide complexes of Cu(II) and their effect on in vivo metallothionein synthesis in mice.

Monosaccharide (D-Glc, D-Fru, D-Gal, D-Xyl, D-Rib) and disaccharide (Mal) complexes of Cu(II) were synthesized from two different precursors, viz. [NEt4]2 [CuCl2Br2] and CuCl2.2H2O, in nonaqueous media, and isolated in the solid state. The complexes were found to be primarily dimeric and trimeric and water soluble. These were characterized by diffuse reflectance, aqueous solution absorption, CD, FTIR, magnetic susceptibility, EPR, EXAFS, XANES, and elemental analysis. Aqueous solution stability in the pH range 4-8 was studied by cyclic voltammetry and absorption spectroscopy. The effect of subcutaneously injected Cu-Fru, Cu-Xyl, and Cu-Rib complexes on the in vivo metallothionein synthesis in mice was found to be significant in liver, but not in brain, in accordance with the observed copper accumulation in these tissues.

Transition metal saccharide chemistry and biology: synthesis, characterization, electrochemistry and EPR studies of oxovanadium (IV) complexes of saccharides and their derivatives and in vitro interaction of some of these with ribonuclease and deoxyribonuclease.

Low molecular weight, water-soluble saccharide complexes of oxovanadium(IV) have been synthesized and characterized by analytical, spectroscopic and electrochemical techniques. All the complexes were found to be mononuclear, possessing the VO2+ moiety. These are shown to be hydrolytically and oxidatively stable over a wide range of pH (1-12) and have been extensively characterized by absorption and EPR spectroscopy and by electrochemistry. Several correlations have been drawn from the data generated. Some of these complexes have been demonstrated to possess in vitro RNase inhibition activity with no effect on DNase. This suggests that these molecules closely mimic the substrate portion of the RNase-catalysed RNA hydrolysis and can act as transition-state analogues to RNase.

One electron reduction of vanadate(V) to oxovanadium(IV) by low-molecular-weight biocomponents like saccharides and ascorbic acid: effect of oxovanadium(IV) complexes on pUC18 DNA and on lipid peroxidation in isolated rat hepatocytes.

One electron reduction of vanadate(V) to vanadyl(IV) occurs in the presence of biocomponents, such as, saccharide s and L-ascorbic acid under physiological conditions. The vanadyl(IV) complexes thus generated have been demonstrated to introduce nicks in pUC18 DNA in the absence or in the presence of hydrogen peroxide and also exhibit lipid peroxidation in isolated rat hepatocytes. Thus the reducing and complexing abilities of these molecules may help in understanding the in vivo reduction and the resultant toxicity to cells incubated with vanadate(V).

Metal-saccharide chemistry and biology: saccharide complexes of zinc and their effect on metallothionein synthesis in mice.

Monosaccharide (D-Fru, D-Gal, D-Glc, D-Xyl, and D-Rib) and disaccharide (Mal) complexes of Zn2+ were synthesized using different precursors and isolated in the solid state. These were found to be anionic with a Zn-to-saccharide ratio of 1:1 and 2:1 for monosaccharide and disaccharide complexes, respectively. Electrochemical behaviour in aqueous solution was studied by extensive cyclic voltammetric studies in the pH range 3.7-10.3. The effect of subcutaneously injected Zn-D-Fru, Zn-D-Gal and Zn-D-Glc complexes on the metallothionein synthesis in mice was found to be significant in the liver, but not in the brain.

In vitro reduction of Cr(VI) by low molecular weight biomimetic components: a comparative study using UV-Vis spectroscopy.

Chromium(VI) reduction has been carried out by a variety of molecules of cellular and soil importance, such as thiol containing ones, ascorbic acid, saccharides and their derivatives, and nucleotides and their components using absorption spectroscopy. Based on the absorption data, the reductive abilities of these molecules have been obtained and the trend has been found to be ascorbic acid > thiols >> saccharides > nucleotides.

In vitro reducing abilities towards chromate of various hydroxy-containing compounds, including saccharides and their derivatives.

The reduction of potassium chromate has been carried out with a variety of OH-containing compounds as reductants, which include pentoses, polyols, glycols, and sugar derivatives. The corresponding reactions were followed using UV-vis and EPR spectroscopies and electrochemistry. The progress of the chromate reduction reactions has been monitored by measuring UV-vis and EPR spectra as a function of time. The observed pseudo first-order reaction rate constants are derived based on the changes in the intensities of the Cr(VI), Cr(V), and Cr(III) signals. Cyclic voltammograms of the simple reductants and their final Cr(III) products formed from the reactions of chromate have also been measured. The reductive abilities of all these reductants have been derived from the spectral data and are discussed on a comparative basis. Based on the results, the aspects that makes a particular reductant more efficient has been addressed. The results obtained from UV-vis, EPR, and cyclic voltammetry are found to be mutually dependent and exhibit among themselves a linear correlation, suggesting that both the reducing and complexing nature of these molecules play important roles in the chromate reduction.

Implementation of nutrition care service development plan at Banning Memorial Hospital: a case study.

Health care service markets in general and hospital care service markets in particular are characterized by many competitive developments. Hence, hospital marketing managers are forced to respond to these emerging competitive pressures. However, in formulating appropriate marketing management strategies, hospital managers need to have detailed knowledge about consumers and their behaviors in the marketplace. This paper focuses on the Nutrition Care division of the Department of Nutrition Service at a hospital and its venture into new service development. This case study is intended to emphasize the significance of acquiring adequate knowledge of customers in the health care services industry. It particularly emphasizes the critical role that this type of information concerning customer behavior plays in the development and implementation of an appropriate business expansion strategy. Furthermore, the aim of this case study is to help the reader to relate the acquired marketing information to the problem at hand, and make the appropriate marketing management decision.