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In healthy eyes, the tear film lipid layer (TFLL) is considered to act as an evaporation resistant barrier, which prevents eyes from drying. Seeking to understand the mechanisms behind the evaporation resistance of the TFLL, we studied mixtures of lipid layer wax esters and O-acyl-omega-hydroxy fatty acids. Analyzing their self-assembly and biophysical properties led to new discoveries concerning the structure and function of the TFLL. We discovered how these lipids self-assemble at the air-water interface and form an efficient antievaporative barrier, demonstrating for the first time how the interaction of different tear film lipid species can improve the evaporation resistance compared with individual lipid classes on their own. These results provide a potential mechanism for the evaporation resistance of the lipid layer. In addition, the results serve as a base for the future development of improved dry eye treatments and other applications where the evaporation of water represents a significant challenge.

Halogenation can be utilized for the purposes of labeling and molecular imaging, providing a means to, e.g., follow drug distribution in an organism through positron emission tomography (PET) or study the molecular recognition events unfolding by nuclear magnetic resonance (NMR) spectroscopy. For cancer therapeutics, where often highly toxic substances are employed, it is of importance to be able to track the distribution of the drugs and their metabolites in order to ensure minimal side effects. Labeling should ideally have a negligible disruptive effect on the efficacy of a given drug. Using a combination of NMR spectroscopy and cytotoxicity assays, we identify a site susceptible to halogenation in monomethyl auristatin F (MMAF), a widely used cytotoxic agent in the antibody-drug conjugate (ADC) family of cancer drugs, and study the effects of fluorination and chlorination on the physiological solution structure of the auristatins and their cytotoxicity. We find that the cytotoxicity of the parent drug is retained, while the conformational equilibrium is shifted significantly toward the biologically active trans isomer, simultaneously decreasing the concentration of the inactive and potentially disruptive cis isomer by up to 50%. Our results may serve as a base for the future assembly of a multifunctional toolkit for the assessment of linker technologies and exploring bystander effects from the warhead perspective in auristatin-derived ADCs.

Glucose- and sodium-dependent glucose transporters (GLUTs and SGLTs) play vital roles in human biology. Of the 14 GLUTs and 12 SGLTs, the GLUT1 transporter has gained the most widespread recognition because GLUT1 is overexpressed in several cancers and is a clinically valid therapeutic target. We have been pursuing a GLUT1-targeting approach in boron neutron capture therapy (BNCT). Here, we report on surprising findings encountered with a set of 6-deoxy-6-thio-carboranyl d-glucoconjugates. In more detail, we show that even subtle structural changes in the carborane cluster, and the linker, may significantly reduce the delivery capacity of GLUT1-based boron carriers. In addition to providing new insights on the substrate specificity of this important transporter, we reach a fresh perspective on the boundaries within which a GLUT1-targeting approach in BNCT can be further refined.

Purpose of the study: Explore perceptions, expectations and challenges following a telerehabilitation programme using augmented reality glasses (ARG) in patients with idiopathic pulmonary fibrosis (IPF), chronic obstructive pulmonary disease (COPD) or recently diagnosed myocardial infarction (MI). Materials and Methods: A qualitative approach was employed to track perspectives from a range of patients with chronic lung and/or heart diseases. COPD, IPF and MI outpatients from Denmark and Finland were invited to participate. Data were collected through focus group and semi-structured in-depth interviews. Qualitative analysis was performed using standard thematic analytical approaches. A topic guide was used to explore experiences and perceptions of the ARG telerehabilitation device among participants. Results: Thirteen patients (4 MI, 2 IPF and 7 COPD), 3 women and 10 men aged 56 to 75 years (mean age 63.3 years) were allocated into one focus group (9 patients) and 4 interviews (4 patients). Twelve patients reported the added value of ARG and suggested constructive changes such as the adjustable screen/brightness, robust head fixation for exercise performance, easy to navigate interface and supported feedback based on exercise performance. Conclusion: Patients with chronic heart or lung diseases described the added value in an ARG telerehabilitation programme. Improvements for a future version of the ARG were suggested.IMPLICATIONS FOR REHABILITATION Patients with chronic pulmonary and heart diseases have difficulties to change behaviour to a more active and healthy lifestyle, offers from the health sector to participate in rehabilitation programmes at the hospital are feasible and improves quality of life and exercise capacity. Not all the patients are capable of participating in such rehabilitation programmes due to frailty and long distance to the hospital. Telerehabilitation seems to be a potential treatment to cope with the needs expressed above. Patient involvement in the development of a telerehabilitation solution to empower chronic pulmonary and heart patients to train, ensures a positive contribution to the design of the expected augmented reality software and hardware envisioned solution for telerehabilitation. The development of a user-centered telerehabilitation platform responding to the preferences of patients with chronic disease will remove barriers that limit use and compliance and improve empowerment in future research projects.

In healthy eyes, the tear film lipid layer (TFLL) is considered to act as an evaporation resistant barrier, which prevents eyes from drying. Seeking to understand the mechanisms behind the evaporation resistance of the TFLL, we studied mixtures of lipid layer wax esters and

The aim of this study was to assess what properties of the pseudostationary phases in electrokinetic capillary chromatography affect the interactions between monomethyl auristatin E (MMAE) and hydrophilically modified structural analogues thereof with various lipophilic phases. MMAE is a widely used cytotoxic agent in antibody–drug conjugates (ADC), which are used as selective biopharmaceutical drugs in the treatment of cancers. MMAE and its derivatives are highly lipophilic, yet they fail to interact with biomimicking phosphatidylcholine–phosphatidylserine liposomes. To reveal what properties affect the interaction of the auristatin derivatives with cell plasma membrane-mimicking vesicles, capillary electrokinetic chromatography was used with four different types of micellar and vesicular pseudostationary phases: pure vesicles, mixed vesicles, mixed micelles, and pure micelles. Vesicular phases were composed of pure phospholipids [dimyristoylphosphatidylcholine (DMPC) and dilauroylphosphatidylcholine (DLPC)] and phospholipid–surfactant mixtures [sodium dodecyl sulfate, (SDS) with DMPC and DLPC] while the micellar phases comprised pure surfactant (SDS) and surfactant–phospholipid mixtures (SDS–DMPC and SDS–DLPC). In addition, differential scanning calorimetry and dynamic light scattering were used to monitor the aggregate composition. Our data shows that the interaction between hydrophobic auristatin derivatives and hydrophobic pseudostationary phases critically depends on the type, size, and hydrogen bonding capability of the pseudostationary phases.

The tear film lipid layer (TFLL) is important to the maintenance of ocular surface health. Surprisingly, information on the individual roles of the myriad of unique lipids found therein is limited. The most abundant lipid species are the wax esters (WE) and cholesteryl esters (CE), and, especially their branched analogs. The isolation of these lipid species from the TFLL has proved to be tedious, and as a result, insights on their biophysical profiles and role in the TFLL is currently lacking. Herein, we circumvent these issues by a total synthesis of the most abundant iso-methyl branched WEs and CEs found in the TFLL. Through a detailed characterization of the biophysical properties, by the use of Langmuir monolayer and wide-angle X-ray scattering techniques, we demonstrate that chain branching alters the behavior of these lipid species on multiple levels. Taken together, our results fill an important knowledge gap concerning the structure and function of the TFLL on the whole.

Boron neutron capture therapy (BNCT) is a noninvasive binary therapeutic modality applicable to the treatment of cancers. While BNCT offers a tumor-targeting selectivity that is difficult to match by other means, the last obstacles preventing the full harness of this potential come in the form of the suboptimal boron delivery strategies presently used in the clinics. To address these challenges, we have developed delivery agents that target the glucose transporter GLUT1. Here, we present the chemical synthesis of a number of

This review is the counterpart of a 2018 Chemical Reviews article that examined the mechanisms of chemical glycosylation in the absence of stereodirecting participation. Attention is now turned to a critical review of the evidence in support of stereodirecting participation in glycosylation reactions by esters from either the vicinal or more remote positions. As participation by esters is often accompanied by ester migration, the mechanism(s) of migration are also reviewed. Esters are central to the entire review, which accordingly opens with an overview of their structure and their influence on the conformations of six-membered rings. Next the structure and relative energetics of dioxacarbeniun ions are covered with emphasis on the influence of ring size. The existing kinetic evidence for participation is then presented followed an overview of the various intermediates either isolated or characterized spectroscopically. The evidence supporting participation from remote or distal positions is critically examined and alternative hypotheses for the stereodirecting effect of such esters is presented. The mechanisms of ester migration are first examined from the perspective of glycosylation reactions, and then more broadly in the context of partially acylated polyols.

Soft nanoparticles are interesting materials due to their size, deformability, and ability to host guest molecules. Surface properties play an essential role in determining the fate of the particles in biological medium, and coating of the nanoparticles (and polymers) with carbohydrates has been found to be an efficient strategy for increasing their biocompatibility and fine-tuning other important properties such as aqueous solubility. In this work, soft nanogels of poly(N-vinylcaprolactam), PNVCL, were surface-functionalized with different glucose and maltose ligands, and the colloidal properties of the gels were analyzed. The PNVCL nanogels were first prepared via semibatch precipitation polymerization, where a comonomer, propargyl acrylate (PA), was added after preparticle formation. The aim was to synthesize “clickable” nanogels with alkyne groups on their surfaces. The nanogels were then functionalized with two separate azido-glucosides and azido-maltosides (containing different linkers) through a copper-catalyzed azide–alkyne cycloaddition (CuAAc) click reaction. The glucose and maltose bearing nanogels were thermoresponsive and shrank upon heating. Compared to the PNVCL–PA nanogel, the carbohydrate bearing ones were larger, more hydrophilic, had volume phase transitions at higher temperatures, and were more stable against salt-induced precipitation. In addition to investigating the colloidal properties of the nanogels, the carbohydrate recognition was addressed by studying the interactions with a model lectin, concanavalin A (Con A). The binding efficiency was not affected by the temperature, which indicates that the carbohydrate moieties are located on the gel surfaces, and are capable of interacting with other biomolecules independent of temperature. Thus, the synthesis produces nanogels, which have surface functions capable of biorelevant interactions and a thermoresponsive structure. These types of particles can be used for drug delivery.

Dry eye syndrome (DES) is a prevalent disease in which the tear film homeostasis is compromised. One of the main causes of DES is thought to be an alteration in the composition of the outermost layer of the tear film, the tear film lipid layer (TFLL), resulting in an increased evaporation of water from the tear film and subsequent drying of the ocular surface. Recent studies have suggested that the specific TFLL lipids, namely, O-aryl-omega-hydroxy fatty acids (OAHFAs) and diesters (DiEs), may play a role in the development of DES. However, their specific connection to DES has remained largely unknown until now because of the lack of information on their biophysical properties and their role in the TFLL. Herein, we have addressed this issue by studying the biophysical properties and evaporation resistance of a library containing 10 synthetic analogues of TFLL OAHFAs and DiEs. Our results show how the variations of chain length and polar groups affect the phase behavior of these lipids at the tear film surface. In addition, the results revealed that the OAHFAs exhibiting a liquid-expanded to solid phase transition formed films with high evaporation resistance, whereas the DiEs were found to have no evaporation resistance. Altogether, our results shed new light on the role of the OAHFAs and DiEs in the TFLL and their connection to DES, suggesting that OAHFAs are likely a key lipid class in maintaining the TFLL evaporation resistance.

One of the most successful bioconjugation strategies to date is the copper(I)-catalyzed cycloaddition reaction (CuAAC), however, the typically applied reaction conditions have been found to degrade sensitive biomolecules. Herein, we present a water soluble copper chelator which can be utilized to protect biomolecules from copper induced degradation.

Antibody–drug conjugates (ADCs) are promising alternatives to naked antibodies for selective drug-delivery applications and treatment of diseases such as cancer. Construction of ADCs relies upon site-selective, efficient and mild conjugation technologies. The choice of a chemical linker is especially important, as it affects the overall properties of the ADC. We envisioned that hydrophilic bifunctional chemical linkers based on carbohydrates would be a useful class of derivatization agents for the construction of linker–drug conjugates and ADCs. Herein we describe the synthesis of carbohydrate-based derivatization agents, glycolinker–drug conjugates featuring the tubulin inhibitor monomethyl auristatin E and an ADC based on an anti-EGFR antibody. In addition, an initial in vitro cytotoxicity evaluation of the individual components and the ADC is provided against EGFR-positive cancer cells.

Many different glycoconjugates, including saponins (e.g., hellebrin) and anthracyclines (e.g., doxorubicin), are known to display cytotoxic activities. In recent work, we have developed synthetic protocols for the synthesis of various glycoconjugates, focusing on glycosylation methods for different classes of biomolecules. Simultaneously a number of saponins and anthracyclines have been generated. In this note, the cytotoxic activities of these synthesized compounds are briefly addressed.

A method for the glycosylation of anthracyclines featuring benzoylated imidate donors has been developed and utilized in the synthesis of glycosylated 4-deoxy-ε-rhodomycinone derivatives. Due to its high efficiency, regioselectivity, stereoselectivity, and operational simplicity, the method should prove valuable to researchers working with glycosylation of tetracyclic compounds.

Hellebrin and transvaalin are two naturally occurring saponins with biological activity. In the present paper, we describe a high yielding route to the synthesis and coupling of their shared glycone, scillabiose, to a model steroid. A convergent coupling strategy utilizing a scillabiose-based glycosyl donor was devised for the glycosylation. This convergent approach is appealing due to its high efficiency and simple deprotection procedure and may find further use in total synthesis of naturally occurring saponins and related compounds sharing the same glycone. Due to the widespread occurrence of this glycone in nature, the complete NMR spectroscopic characterization of all compounds prepared herein is provided as reference material. In addition, glycosylations were performed with the monosaccharide constituents of scillabiose, thereby providing a limited series of glycosylated steroids for potential future evaluation of the effects of the glycone on the overall biological activity.

Glycosylated steroids, such as cardenolides and saponins, are widely distributed in nature and have been shown to possess various types of biological activities. In the present study, carbohydrate donors were evaluated for the glycosylation of steroids; the results show that benzoylated imidate donors were superior in terms of efficiency and operational simplicity. These donors were then applied to the synthesis of a limited library of estradiol-based glycosteroid mimics containing a modified D-ring. The deprotected molecules contained three types of variations in the steroid backbone and four types of variations in the sugar moiety. The synthesized structures will be screened for biological activity and for their potential use in drug delivery systems.

Fully acetylated D- and L-α-mannosylacetaldehydes have been prepared and used as substrates to produce the corresponding cyanohydrins or cyanohydrin acetates with (2S) or (2R) configuration, respectively, at the cyanohydrin moiety. The (R)-oxynitrilase-catalysed synthesis and lipase-catalysed diastereomeric kinetic and dynamic kinetic resolutions were investigated. Sequential catalysis with almond meal [an economic source of (R)-oxynitrilase] and Burkholderia cepacia lipase was shown to be a straightforward method that yielded the four diastereomeric target cyanohydrins, the absolute configurations of which were confirmed by 1 H NMR analysis.

A convenient semi-synthesis of ( 8R , 8 ′ R )-matairesinol 4,4′-di- O -β- d -glucopyranoside (MDG), found in the stems of Trachelospermum asiaticum var. intermedium , is described starting from the readily available starting materials d -glucose and hydroxymatairesinol. By this approach the synthesis of MDG can be accomplished in six steps with an overall yield of 28%. In addition, the first complete NMR-spectroscopic characterization of MDG was accomplished by the combination of standard NMR techniques and spectral simulations performed with the PERCH NMR simulation software.

β-(1→2)-Linked oligomannosides constitute an important class of carbohydrate structures located on the cell surface of several Candida species, including C. albicans. As a result of the immunostimulating properties of such compounds, the upscaling of their synthesis is relevant. In this paper, a highly stereoselective synthesis of β-(1→2)-linked oligomannosides was performed by further development of and modifications to the methodologies described earlier in the literature. In addition to the synthesis of fully deprotected β-(1→2)-linked mannobiose and mannotriose, some preliminary modifications to the oligosaccharide core, resulting in close analogues with biological potential, are presented. The fully deprotected products form potential targets for screening against C. albicans and may also result in new model structures for vaccine development.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

Several studies have implicated (1→2)-linked mannans as biologically relevant compounds. Recently, there has been a growing interest in the synthesis of multivalent carbohydrate assemblies due to their ability to target multiple receptors simultaneously. In the present work, a protective group strategy, based on the methodology originally developed by Crich, has been utilized for the homodimerization of olefinic carbohydrates, allowing a highly diastereoselective synthesis of some divalent structures. Furthermore, it is shown that divalent donors may undergo coupling reactions without losses in stereoselectivity or efficiency. The strategies described may potentially be applied to the synthesis of diverse neoglycoconjugates and oligosaccharides.

The European Space Agency's Soil Moisture and Ocean Salinity satellite comprises a single payload instrument known as the Microwave Interferometric Radiometer with Aperture Synthesis (MIRAS) coupled to a PROTEUS platform. MIRAS synthesizes a large aperture from a reasonably sized 2-D array of passive microwave radiometers. By using interferometric techniques, the required coverage and spatial resolution can be achieved without the need for a large antenna. This paper describes the MIRAS instrument, its observation modes, the imaging geometry, and data products.

A rapid, simple, and efficient deprotection procedure for the deprotection of benzyl- and/or benzylidene protected carbohydrates is described utilizing a continuous flow hydrogenation reactor. The method tolerates both acid- and base sensitive functional groups. The high efficiency, simple work-up, and short reaction time should make this method appealing to researchers working in the fields of carbohydrate chemistry and total synthesis.

Immunostimulatory properties of synthetic structures mimicking the β-(1→2)-linked mannans ofCandida albicanswere evaluatedin vitro. Contrary to earlier observations, tumor necrosis factor (TNF) production was not detected after stimulation with mannotetraose in mouse macrophages. Divalent disaccharide 1,4-bis(α-d-mannopyranosyloxy)butane induced TNF and some molecules induced low levels of gamma interferon (IFN-γ) in human peripheral blood mononuclear cells (PBMC).

This paper describes the RETE (Research on Electrodynamic Tether Effects) experiment mounted on board the TSS (Tethered-Satellite System) satellite which was deployed on a cable from the space Shuttle Atlantis during the TSS mission flown in August 1992. The experiment layout and its modes of operation are described in detail. To give an idea of RETE capabilities and actual performance during the mission, samples of measurements are also presented.

Hereditary diffuse leukoencephalopathy with spheroids (HDLS) was first identified among a Swedish kindred with 17 cases. The average age of onset was 36 years. Autopsy in four cases revealed the presence of axonal spheroids. The causative gene is unknown.We performed genealogical and longitudinal observations of the original kindred. Forty members were examined, five telephone-interviewed, and one of the original HDLS cases from 1984 was neuropathologically examined. The clinical course was documented. The cerebrospinal fluid (CSF) findings of two recently affected cases were examined, and one of those autopsied.Of those examined, two developed HDLS during our survey and 38 were healthy. Those interviewed by telephone were healthy. One had symptoms suggestive of HDLS in 1984, but autopsy during our survey showed no spheroids. This patient, two relatives healthy at our examination and one without symptoms at telephone interview had HDLS diagnoses in the 1984 report. Thus, four HDLS diagnoses were unconfirmed. The number of identified patients amounts to 15 among 75 individuals in four generations, including two recent cases who demonstrated a subacute multisystem encephalopathy in Case 1 and an insidious course in Case 2. CSF showed signs of neurodegeneration without inflammation, and autopsy verified HDLS in Case 1.Some HDLS cases were misdiagnosed with unspecified psychiatric diagnoses in affected relatives from the original 1984 publication. However, HDLS is an encephalopathy dominated by a frontal lobe syndrome with an inexorably progressive and fatal course, where the different symptomatology in two recent cases confirmed the existence of acute and chronic variants.

The clinical value in neuropediatrics of [99mTc]HM-PAO brain single photon emission computed tomography was preliminary evaluated by the consecutive investigation of 79 children. Planned epilepsy surgery was the most common indication for the investigation. In 56 children investigated because of epilepsy, SPECT yielded relevant information in 79% of cases examined. The corresponding figures for magnetic resonance imaging and CT were 49% of 35 and 36% of 56 cases, respectively. All 22 children with an epileptic focus, ascertained by freedom from seizures after removal of the area or by consistent neurophysiological and neuroradiological findings, also had abnormal perfusion in the relevant area. Twenty-three children were examined because of neurological signs and symptoms other than epilepsy. SPECT findings were useful for elucidating neonatal brain impairments. Hypoperfused areas in the brain of asphyxiated infants and in posthemorrhagic hydrocephalus corresponded to neuroradiological and autopsy findings. SPECT was found to be an excellent tool when analysing cerebrovascular accidents. In cases with signs and symptoms of a diffuse severe encephalopathy, SPECT did not clarify the etiology but provided information on the distribution of the lesions and probable underlying pathophysiological mechanisms.

Changes in concentration of high energy phosphates and pH were studied during rest, exercise and subsequent recovery in the anterior tibial muscle of 10 patients with late effects of poliomyelitis and 10 age- and sex-matched healthy volunteers using 31P MRS. The exercise was dynamic and isometric, and the force levels were individually adapted to each subject and stepwise increased. In general, there were no differences in metabolite changes between the groups, except for lower Pi and Pi/PCr for the volunteers during the recovery phase, also reflected by shorter recovery half-time for Pi. The interindividual variation was much higher for the patient group. Some of the patients showed deviating results probably because of differences in muscle fibre type.

The LindqvistMalmgren's system was used to describe the outcome of organic psychiatric disorders (OPDs) after aneurysmal subarachnoid hemorrhage (aSAH) and their associations with age, bleeding severity, and pre-existing arterial hypertension (preAH).OPDs were diagnosed at 3, 6, and 12 months after aSAH in a prospective cohort study (n=63). Reaction level (RLS85), World Federation of Neurological Surgeons Committee SAH scale (WFNS), Fisher, and hydrocephalus grades were assessed at admission.At 3/6/12 months, 60/49/38% had an Astheno-emotional disorder (AED), 4/5/5% had emotional-motivational blunting disorder (EMD) and 19/19/16% had Korsakoffs amnestic disorder (KAD). AED was associated with preAH, whereas EMD/KAD, but not AED, was associated with a higher mean age, worse median RLS85 levels, WFNS grades, and Fisher grades.OPDs were diagnosed in 59% of the patients at 12 months after aSAH. AED, the most common OPD, had the highest recovery rate and was associated with preAH. Use of organic psychiatric diagnoses for evaluation of outcome after aSAH and other brain injuries is encouraged.

To analyse the diagnostic and prognostic value of periventricular hyperintensity (PVH) and deep white matter hyperintensity (DWMH) magnetic resonance imaging (MRI) changes and their relation to symptoms and cerebrospinal fluid (CSF) markers of demyelination (sulphatide) and axonal degeneration [neurofilament triplet protein (NFL)] in a large series of patients with normal pressure hydrocephalus (NPH) and Binswanger disease (BD).PVH and DWMH were determined by a semi-automatic segmentation method on T2-weighted images in 29 patients with NPH and 17 patients with BD. CSF analyses, psychometric testing and quantification of balance, gait and continence were performed in all patients and also postoperatively in NPH patients.No MRI variable could identify NPH or BD patients. Abundant PVH and DWMH preoperatively correlated with improvement in gait, balance and psychometric performance after shunt surgery (P0.05). CSF sulphatide correlated positively with the amount of DWMH (P0.05) while NFL was correlated to both PVH and DWMH (P0.05). Abundant PVH correlated with poor psychometric performance while DWMH correlated with gait disturbance (P0.05). Postoperative reduction in PVH correlated with improvement in gait, balance and psychometric performance.In spite of a refined quantification method, NPH and BD patients exhibited similar MRI changes. MRI had a predictive value in NPH patients. DWMH might relate to demyelination and PVH to neuronal axonal dysfunction. NPH and BD share the major part of symptoms and MRI changes, indicating a common pathophysiological pattern, and we raise the question of how to treat BD patients.

Image selected in vivo spectroscopy (ISIS) is a volume selection method often used for in vivo (31)P MRS, since it is suitable for measurements of substances with short T(2). However, ISIS can suffer from significant signal contributions caused by T(1) smearing from regions outside the VOI. A computer model was developed to simulate this contamination. The simulation results for the ISIS experiment order implemented in our MR system (ISIS-0) were in agreement with results obtained from phantom measurements. A new extended ISIS experiment order (E-ISIS) was developed, consisting of four "optimal" ISIS experiment orders (ISIS-1 to ISIS-4) performed consecutively with dummy ISIS experiments in between. The simulation results show that contamination due to T(1) smearing is, effectively, eliminated with E-ISIS and is significantly lower than for ISIS-0 and ISIS-1. E-ISIS offers increased accuracy for quantitative and qualitative determination of substances studied using in vivo MRS. Hence, E-ISIS can be valuable for both clinical and research applications.

Anatomical and neurological correlates of visuospatial neglect were studied in 53 patients with a CT-documented right hemisphere stroke. Evidence of neglect at the acute stage poststroke was strongly related to large lesions involving the middle temporal gyrus and/or the temporo-parietal paraventricular white matter. Thus, out of 18 patients with evidence of visuospatial neglect at the acute stage, 12 showed a lesion in the middle temporal gyrus and/or the deep temporo-parietal white matter. Among the 35 patients that failed to show visuospatial neglect, only one patient had a lesion within these areas. Comparing those patients who recovered from neglect with those that did not, a high correlation was found between persisting neglect and a lesion involving the paraventricular white matter in the temporal lobe. On the basis of above findings, it was suggested that a simultaneous damage to the cortico-thalamic system for regulation of arousal and to the neural systems mediating visual orienting, is likely to be followed by persisting neglect symptoms.

Image quality in preimplant computerized tomography (CT) examinations made with different radiation doses (40 to 280 mAs) and scanning modes (standard and helical axial, 15-degree angled, and frontal) and in conventional spiral tomography (Scanora) was compared. Mandibular canal and alveolar bone crest visibility was evaluated in images from mandibular jaw segments. Visibility was unaffected by radiation dose in CT examinations except in frontal scanning, where a small actual difference was statistically significant. Differences among CT scanning modes and between CT and conventional spiral tomography were highly significant. Low-dose mandibular preimplant tomography can be performed with CT using lower-than-normal radiation doses or with conventional spiral tomography.

The addition of sodium to nonionic contrast media has reduced the incidence of arrhythmias in animal models. The influence on cardiac function and safety of sodium addition to the nonionic contrast medium iohexol (Omnipaque) was studied in a randomized, double-blind trial in patients undergoing cardioangiography. Fifty-nine patients received iohexol 350 mg I/ml with NaCl 28 mmol/l and 58, iohexol only. ECG changes after contrast injections were evaluated with continuous computerized dynamic vectorcardiography (VCG). QRS-vector difference (QRS-vd), which reflects changes in the QRS-complex, was chosen as the main parameter. Both contrast media caused changes in the QRS-complex, but there was no significant difference between the two. No serious arrhythmias were observed. Both contrast media were well tolerated. No beneficial effects from enriching iohexol with sodium were found. VCG was found to be a valuable tool in the study of contrast medium-induced ECG changes.

β-(1→2)-linked oligomannosides, found in the cell wall of Candida albicans, are promising structures for the development of C. albicans vaccines. Considerable effort in recent years has been devoted to the synthesis of these carbohydrate structures. As a result, several successful synthetic methodologies based on linear approaches have emerged. Here, we demonstrate that a fully deprotected β-(1→2)-linked mannotetrasaccharide can also be conveniently constructed by the convergent direct coupling of two appropriately protected disaccharides. This improved approach offers several advantages over previously published methods. The number of steps needed to reach larger oligosaccharides is decreased, while high selectivity is retained when the crucial glycosylation step is performed with two disaccharides, herein providing β-(1→2)-mannotetraose in 4.2% overall yield over 16 steps starting from D-mannose. Additionally, the complete structural characterization of the products by NMR spectroscopy is reported. In the conformational study of the final product, 2D-NOESY was used in combination with spectral simulations performed using PERCH software. The experimental results obtained confirm the contorted α-helical structure predicted earlier for these oligosaccharides in solution. As a culmination of the conformational study, a model was constructed by molecular modeling using DFT, and the minimum energy conformation was found to be in full agreement with the experimental results. This is the first study to date where the conformation of a fully deprotected mannotetraose has been reported.

Surgery was performed in the maxillary sinus with restoration of the surgical defect in the anterior wall with a resutured bone-lid, in 12 patients with an average age of 45 years, the technique is described and evaluated clinically and radiographically (computed tomography). During the followup time of 1-4 years, the condition of the maxillary sinus was normalized. It is our opinion that the bone-lid technique for maxillary sinus surgery is useful, especially when good overview and access is necessary.

The cardiovascular and ventilatory effects of centrally and peripherally administered melatonin were examined in both normotensive rats (NTR) and in spontaneously hypertensive rats (SHR). In the experiments on anaesthetised NTR melatonin was administered intravenously at doses of 1, 10, and 100 mumol/kg, or intracerebroventricularly at doses of 0.01, 0.1, 1, and 10 mumol/kg. In the experiments on conscious SHR melatonin was administered orally at doses of approximately 2 mg per animal per day, or intracerebroventricularly at doses of 0.01, 0.1, 1, and 10 mumol/kg. Melatonin did not produce any significant cardiovascular or ventilatory effects in any of the experiments.

The need for repositioning of surface coils and patients in MR examinations of the cervical and thoracic spine prolongs examination time. A new receiver design is proposed which overcomes this problem. The device is composed of two actively decoupled receiver coils mounted on the frame of a Philadelphia collar. These coils may be used separately to image either the thoracic or cervical spine or together to produce larger field-of-view images of the combined region. Signal-to-noise ratios of the separate cervical and thoracic spine images are not degraded as a result of mounting the receivers together. The full cervical and thoracic region is shown to be imaged at a signal-to-noise ratio significantly higher than that afforded by the body coil. A retrospective review of our case load suggests that a time saving could be achieved in approximately 1/3 of spine examinations by using this coil.