Cold photo-carving of halogen-bonded co-crystals of a dye and a volatile co-former using visible light.

The formation of co-crystals by the assembly of molecules with complementary molecular recognition functionalities is a popular strategy to design or improve a range of solid-state properties, including those relevant for pharmaceuticals, photo- or thermoresponsive materials and organic electronics. Here, we report halogen-bonded co-crystals of a fluorinated azobenzene derivative with a volatile component-either dioxane or pyrazine-that can be cut, carved or engraved with low-power visible light. This cold photo-carving process is enabled by the co-crystallization of a light-absorbing azo dye with a volatile component, which gives rise to materials that can be selectively disassembled with micrometre precision using low-power, non-burning laser irradiation or a commercial confocal microscope. The ability to shape co-crystals in three dimensions using laser powers of 0.5-20 mW-substantially lower than those used for metals, ceramics or polymers-is rationalized by photo-carving that targets the disruption of weak supramolecular interactions, rather than the covalent bonds or ionic structures targeted by conventional laser beam or focused ion beam machining processes.

Thermo-, photo-, and mechano-responsive liquid crystal networks enable tunable photonic crystals.

Tunable photonic crystals exhibiting optical properties that respond reversibly to external stimuli have been developed using liquid crystal networks (LCNs) and liquid crystal elastomers (LCEs). These tunable photonic crystals possess an inverse opal structure and are photo-responsive, but circumvent the usual requirement to contain dye molecules in the structure that often limit their applicability and cause optical degradation. Herein, we report tunable photonic crystal films that reversibly tune the reflection peak wavelength under thermo-, photo- and mechano-stimuli, through bilayering a stimuli-responsive LCN including azobenzene units with a colourless inverse opal film composed of non-responsive, flexible durable polymers. By mechanically deforming the azobenzene containing LCN via various stimuli, the reflection peak wavelength from the bilayered film assembly could be shifted on demand. We confirm that the reflection peak shift occurs due to the deformation of the stimuli-responsive layer propagating towards and into the inverse opal layer to change its shape in response, and this shift behaviour is repeatable without optical degradation.

Computer-aided combined movement examination of the lumbar spine and manual therapy implications: Case report.

Combined movement examination (CME) of the lumbar spine has been recommended for clinical examination as it confers information about mechanical pain patterns. However, little quantitative study has been undertaken to validate its use in manual therapy practice. This study used computer aided CME to develop a normal reference range, and to guide provisional diagnosis and management. Two cases were assessed, before and after manual therapy using CME, a pain Visual Analogue Scale, the Roland Morris Low Back Pain and Disability Questionnaire and the Short Form (SF-12) Health Survey. Diagnosis and management were guided by comparing each CME pattern with the age and gender matched reference range. Self-reports data and CME total change scores were markedly improved for both cases, particularly for the most painful and restricted CME directions. This report describes how computer-aided CME and a normal reference range may be used objectively to inform a diagnosis and as an outcome measure in cases of mechanical LBP. Future investigations of cases with specific lumbar pathologies are required to validate this concept.

Blockade of inhibitors of apoptosis (IAPs) in combination with tumor-targeted delivery of tumor necrosis factor-α leads to synergistic antitumor activity.

In the current study, we examined whether the combination of tumor vasculature-targeted gene therapy with adeno-associated virus bacteriophage-tumor necrosis factor-α (AAVP-TNF-α) and/or the orally administered LCL161, an antagonist of inhibitors of apoptosis proteins (IAPs), enhanced antitumor efficacy without systemic toxicity. M21 human melanoma xenografts were grown subcutaneously in nude mice. Mice were treated according to one of four treatment regimens: AAVP-TNF-α alone (AAVP-TNF-α plus sodium acetate-acetic acid (NaAc) buffer) via tail vein injection; LCL161 alone (phosphate-buffered saline (PBS) plus LCL161) via oral gavage; AAVP-TNF-α plus LCL161; and PBS plus NaAc Buffer as a control group. Tumor volume, survival and toxicity were analyzed. AAVP trafficking and TNF-α production in vivo were detected on days 7 and 21 by real-time PCR, enzyme-linked immunosorbent assay and immunofluorescence. The levels of apoptosis and activation of caspases were assessed on days 7 and 21 by TUNEL (terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling) and immunofluorescence assays. Our results showed that the combination of AAVP-TNF-α and LCL161 significantly inhibited tumor growth and prolonged survival in mice with melanoma xenografts. The combination of AAVP-TNF-α and LCL161 was also significantly more effective than either agent alone, showing a synergistic effect without systemic toxicity.

Long-term control of renal blood flow: what is the role of the renal nerves?

We have developed a system for long-term continuous monitoring of cardiovascular parameters in rabbits living in their home cage to assess what role renal sympathetic nerve activity (RSNA) has in regulating renal blood flow (RBF) in daily life. Blood pressure, heart rate, locomotor activity, RSNA, and RBF were recorded continuously for 4 wk. Beginning 4-5 days after surgery a circadian rhythm, dependent on feeding time, was observed. When averaged over all days RBF to the innervated and denervated kidneys was not significantly different. However, control of RBF around these mean levels was dependent on the presence of the renal sympathetic nerves. In particular we observed episodic elevations in heart rate and other parameters associated with activity. In the denervated kidney, during these episodic elevations, the increase in renal resistance was closely related to the increase in arterial pressure. In the innervated kidney the renal resistance response was significantly more variable, indicating an interaction of the sympathetic nervous system. These results indicate that whereas overall levels of RSNA do not set the mean level of RBF the renal vasculature is sensitive to episodic increases in sympathetic nerve activity.

Stable sensor layers self-assembled onto surfaces using azobenzene-containing polyelectrolytes.

Polyelectrolytes functionalized with photoisomerizable azobenzene chromophores were multi-layered onto inorganic and metal surfaces, by the repeated adsorption from dilute aqueous solution, alternating between oppositely charged polymers. These layer-by-layer ionically self-assembled thin films were investigated for their suitability as sensor host materials with respect to the criteria of control over physical layer properties, versatility to different substrates and adsorption geometries, and stability of the formed layers to heat, solvent, and sonication. Layer thickness was found to be controllable between 5 A and 500 nm by varying the total number of layers deposited, from a single monolayer to 1000 layers. Control over individual layer thickness was achieved by varying the pH of the adsorption solutions. This multi-layer self-assembly was demonstrated to be suitable for a wide range of metal and inorganic substrates, and achievable with surfaces of high curvature (r = 50 nm), and confined geometry. The deposited layers exhibited good stability to desorption in a range of organic solvents, aqueous temperatures to 100 degrees C, and cleaning protocols such as sonication. The laser-induced geometric isomerization of the azobenzene chromophores was shown to be strongly dependent on aqueous solution properties, demonstrating an application as a hydroxide ion sensor in highly alkaline media.

Oxidative stress impairs cardiac chemoreflexes in diabetic rats.

We investigated the effects of diabetes mellitus and antioxidant treatment on the sensory and reflex function of cardiac chemosensory nerves in rats. Diabetes was induced by streptozotocin (STZ; 85 mg/kg ip). Subgroups of sham- and STZ-treated rats were chronically treated with an antioxidant, vitamin E (60 mg/kg per os daily, started 2 days before STZ). Animals were studied 6-8 wk after STZ injection. We measured renal sympathetic nerve activity (RSNA), mean arterial blood pressure (MABP), and cardiac vagal and sympathetic afferent activities in response to stimulation of chemosensitive sensory nerves in the heart by epicardial application of capsaicin (Caps) and bradykinin (BK). In cardiac sympathetic-denervated rats, Caps and BK (1-10.0 microg) evoked a vagal afferent mediated reflex depression of RSNA and MABP, which was significantly blunted in STZ-treated rats (P < 0.05). In vagal-denervated rats, Caps and BK (1-10.0 microg) evoked a sympathetic afferent-mediated reflex elevation of RSNA and MABP, which also was significantly blunted in STZ-treated rats (P < 0.05). Chronic vitamin E treatment effectively prevented these cardiac chemoreflex defects in STZ-treated rats without altering resting blood glucose or hemodynamics. STZ-treated rats with insulin replacement did not exhibit impaired cardiac chemoreflexes. In afferent studies, Caps and BK (0.1 g-10.0 microg) increased cardiac vagal and sympathetic afferent nerve activity in a dose-dependent manner in sham-treated rats. These responses were significantly blunted in STZ-treated rats. Vitamin E prevented the impairment of afferent discharge to chemical stimulation in STZ rats. The following were concluded: STZ-induced, insulin-dependent diabetes in rats extensively impairs the sensory and reflex properties of cardiac chemosensitive nerve endings, and these disturbances can be prevented by chronic treatment with vitamin E. These results suggest that oxidative stress plays an important role in the neuropathy of this autonomic reflex in diabetes.

Assessment of combined movements of the lumbar spine in asymptomatic and low back pain subjects using a three-dimensional electromagnetic tracking system.

Combined movement examination (CME) is used by physiotherapists to assess and treat patients with low back pain (LBP). However, this method has not been subjected to quantitative assessment. The purpose of this study was to discover if CME of the lumbar spine could be measured with acceptable intra-examiner reliability and to make a preliminary investigation of the effect of LBP on the results of CME. Combined movement examination of the human thoracolumbar spine was measured using a three-dimensional electromagnetic goniometer (3SPACE Fastrak Polhemus, Colchester, Vermont, USA). 1. Intra-examiner reliability of CME was evaluated using a test-retest design; examination was repeated in 23 subjects without LBP and 16 with LBP. 2. A sample of 31 subjects without LBP and 23 subjects with LBP underwent CME, which involved measuring right and left sideflexion in the flexed, neutral and extended position. Pearson's r and the intraclass correlation coefficient for all variables ranged from 0.79 to 0.93 (P < 0.05). A MANOVA test (P < 0.05), comparing the combined effects of the two variables for each position, was used to test for a difference between the positions attained by the subjects with LBP and those without. Generally LBP subjects showed smaller ranges of movement than those without LBP. Each position was recorded as a degree of rotation around the x-axis (flexion/extension) and around the y-axis (left and right sideflexion). CME can be carried out with acceptable intra-examiner reliability; preliminary evidence is presented concerning the effectiveness of CME in identifying reduced spinal movement in LBP subjects.

Sympathoinhibitory effects of atrial natriuretic peptide in rats with heart failure.

BACKGROUND: It has been suggested that a blunted sympathoinhibitory response to atrial natriuretic peptide (ANP) may contribute to the elevation of sympathetic activity seen in heart failure. METHODS AND RESULTS: Experiments were performed in anesthetized rats 6 to 9 weeks after coronary ligation to induce heart failure. Responses to intravenous injections of ANP (4 microg/kg) did not differ between the sham-operated (n = 11) and heart-failure (n = 7) rats. Before sinoaortic denervation, ANP decreased mean arterial pressure (MAP) by 8 mm Hg in both the heart-failure and sham rats, renal sympathetic nerve activity (RSNA) by 9% to 10% in both groups, and heart rate (HR) by 12 to 13 beats/min in both groups. After baroreceptor denervation, ANP decreased MAP by approximately 22 mm Hg, RSNA by 14%, and HR by 16 beats/min in both the heart-failure and sham rats. After vagotomy, there was no longer a significant decrease in RSNA or HR in response to ANP. CONCLUSION: The sympathoinhibitory effects of ANP are maintained in heart failure. This suggests that the elevated sympathetic activity observed in heart failure cannot be attributed to a blunting of the response to ANP.

The intrinsic rate response of the isolated right atrium of the rat, Rattus norvegicus.

Experiments were performed on rat right atria maintained at 37 degrees C in oxygenated Krebs-Henseleit solution, at a baseline diastolic transmural pressure of 2 mmHg. A step increment in right atrial pressure caused an increase in atrial rate which reached a steady value after 2-3 min (rate response). An 8-mmHg increase in atrial pressure caused an 8% increase in atrial rate (n = 9, P < 0.01). When the atrial rate was reduced by carbamylcholine, the rate response was augmented. After a 34% reduction in atrial rate, an 8-mmHg increase in atrial pressure increased atrial rate by 51% (n = 7, P < 0.01). When atrial rate was elevated 71% by isoprenaline, the rate response was reversed (atrial rate decreased 3% following an 8-mmHg increase in atrial pressure; n = 7, P < 0.01). In another series of experiments, atrial rate was adjusted to a wide range of values by exposure to carbamylcholine and isoprenaline, first applied singly, and then in combination. At any given atrial rate, the rate response was always larger when both agonists were present; this difference was greatest when atrial rate was near the control untreated value.

Three-dimensional measurement of lumbar spine kinematics for fast bowlers in cricket.

OBJECTIVE: To determine whether the three-dimensional (3-D) lumbar spine kinematics for the mixed fast bowling technique differed to those of the side-on and front-on fast bowling techniques. BACKGROUND: It has been previously shown that bowlers who utilise a mixed bowling technique are more likely to show lumbar spine pathology than those who bowl with either the side-on or front-on techniques. METHODS: An electromagnetic device (3-Space(R)Fastrak(TM)) operating at 120 Hz captured range of motion and 3-D lumbar spine kinematics during the delivery stride of 20 young high performance subjects. The trajectory of shoulder and pelvic girdle markers were simultaneously captured and these data were used to classify bowlers into either a side-on, front-on or mixed technique group. RESULTS: No significant differences (P<0.004) existed between the side-on/front-on and mixed groups for 12 selected variables derived from the lumbar spine kinematic data. However, an examination of effect sizes revealed evidence that the mixed group showed: a greater amount of left lateral bend and an extended lumbar spine at front foot impact; a body position further from a neutral orientation at lease; and a greater range of motion and angular velocity of the trunk in the lateral bending and flexion/extension axes. CONCLUSIONS: Selected lumbar range of motion and velocity measures tended to be higher for mixed bowlers than side-on/front-on bowlers. RELEVANCE: Overuse injuries to fast bowlers in bricket are common. To better understand the mechanics of injury it is necessary to understand the 3-D rotations of the lumbar spine during this activity.

Release kinetics of fluphenazine from biodegradable microspheres.

Fluphenazine-loaded microspheres were prepared using biodegradable lactide and lactide-co-glycolide polymers. Sustained release of fluphenazine was achieved with fluphenazine loadings of up to 30 per cent in both the lactide and lactide-co-glycolide polymers. Fluphenazine release from microspheres was found to increase with increasing drug loading and was most rapid from the poly-L-lactide-co-glycolide microspheres. The release profiles showed a 'lag' period followed by an accelerating release phase and in some cases a decay period, i.e. the release profiles were sigmoidal and fitted the Prout-Tomkins equation (Prout and Tompkins 1944). Consequently it was considered that polymer degradation, the primary rate-determining step controlling drug release, occurred by a mechanism involving propagation of active sites, drug release reflecting the spread of this degradation throughout the polymer.

The needs of prisoners' wives: a challenge for the mental health professions.

This research assessed the needs of prisoners' wives in six areas (information, finances, relationships with friends, family relationships, grief, and relationships with children) and determined if stage of separation or previous experience with the correctional system affected those needs. High levels of need were found in each area. Women in the initial stage of separation had significantly greater need for information than women in the pre-reunion stage, but prior experience with the correctional system did not predict needs. Results suggest giving more information to the women at the time of their husbands' trials and the formation of self-help groups.

The social network in marijuana-using groups.

Three ongoing marijuana-using groups were studied in their natural environments. Group characteristics and the relationship of each member to individuals within the group were assessed, in addition to the members' primary social roles outside the group. The relationship of sociometric data to user characteristics was determined. The social and drug histories of the three groups were highly similar. Despite high levels of drug use, the most frequent reason for group participation was friendship, and diverse social activities occurred in the group. Social resources outside the group were minimal, whereas enduring, positive relationships characterized each group. Popularity was related to frequency of group participation, but not to extent of drug use. The function of marijuana-using groups in fulfilling interpersonal needs is discussed.