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Aims: Fifteen years ago, we published an article in Social Science and Medicine seeking to resolve the contentious debate between advocates of two very different frameworks for understanding and addressing the mental health needs of conflict-affected populations. The two approaches, which we labelled trauma-focused and psychosocial , reflect deeply held beliefs about the causes and nature of distress in war-affected communities. Drawing on the burgeoning literature on armed conflict and mental health, the reports of mental health and psychosocial support (MHPSS) staff in the field, and on research on the psychology and psychophysiology of stress, we proposed an integrative model that drew on the strengths of both frameworks and underscored their essential complementarity. Our model includes two primary pathways by which armed conflict impacts mental health: directly, through exposure to war-related violence and loss, and indirectly, through the harsh conditions of everyday life caused or exacerbated by armed conflict. The mediated model we proposed draws attention to the effects of stressors both past (prior exposure to war-related violence and loss) and present (ongoing conflict, daily stressors), at all levels of the social ecology; for that reason, we have termed it an ecological model for understanding the mental health needs of conflict-affected populations., Methods: In the ensuing 15 years, the model has been rigorously tested in diverse populations and has found robust support. In this paper, we first summarize the development and key tenets of the model and briefly review recent empirical support for it. We then discuss the implications of an ecological framework for interventions aimed at strengthening mental health in conflict-affected populations., Results: We present preliminary evidence suggesting there has been a gradual shift towards more ecological (i.e., multilevel, multimodal) programming in MHPSS interventions, along the lines suggested by our model as well as other conceptually related frameworks, particularly public health., Conclusions: We reflect on several gaps in the model, most notably the absence of adverse childhood experiences. We suggest the importance of examining early adversity as both a direct influence on mental health and as a potential moderator of the impact of potentially traumatic war-related experiences of violence and loss.

Background: War and violence have a serious negative impact on the wellbeing and mental health of many children. Caregivers play an important role in mitigating or exacerbating this impact., Objective: This study evaluates the impact of the nine session Caregiver Support Intervention on improving children's wellbeing and examines putative mediators of changes in children's psychosocial wellbeing., Participants and Setting: 240 female caregivers were randomly allocated (1:1) to the CSI or a waitlist control comparison condition. The study was implemented in Lebanon, in an area characterized by high levels of poverty and a high number of the Syrian refugees., Methods: A parallel group Randomized Controlled Trial reporting on caregiver-reported child-level wellbeing. We used a combination of the Kid- and Kiddy-KINDL (parent version) for index children ages three to 12. Putative mediators of the CSI on children's psychosocial wellbeing included harsh parenting, caregiver psychological distress, caregiver wellbeing. Measurements were conducted at baseline, post-intervention and 3-months follow-up., Results: We demonstrated a statistically significant change in caregiver reported children's psychosocial wellbeing at post-intervention (Mdiff =4.39, 95 % CI = 1.12, 7.65, p < 0.01, d = 0.28) but not at follow-up (Mdiff = -0.97, 95 % CI = -4.27, 2.32, p > 0.05). The proportion of the total effect of the CSI intervention on child psychosocial wellbeing mediated by caregiver distress, caregiver wellbeing and harsh parenting was 77 %., Conclusion: The CSI holds potential for down-stream short-term effect on improving children's psychosocial wellbeing, beyond the previously reported positive caregiver outcomes. This effect was not sustained three months post intervention. The study confirms caregiver wellbeing and parenting support as dual pathways mediating child psychosocial wellbeing. Prospective trial registration: ISRCTN22321773., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Aims: When the Interagency Standing Committee (IASC) adopted the composite term mental health and psychosocial support (MHPSS) and published its guidelines for MHPSS in emergency settings in 2007, it aimed to build consensus and strengthen coordination among relevant humanitarian actors. The term MHPSS offered an inclusive tent by welcoming the different terminologies, explanatory models and intervention methods of diverse actors across several humanitarian sectors (e.g., health, protection, education, nutrition). Since its introduction, the term has become well-established within the global humanitarian system. However, it has also been critiqued for papering over substantive differences in the intervention priorities and conceptual frameworks that inform the wide range of interventions described as MHPSS. Our aims are to clarify those conceptual frameworks, to argue for their essential complementarity and to illustrate the perils of failing to adequately consider the causal models and theories of change that underlie our interventions., Methods: We describe the historical backdrop against which the term MHPSS and the IASC guidelines were developed, as well as their impact on improving relations and coordination among different aid sectors. We consider the conceptual fuzziness in the field of MHPSS and the lack of clear articulation of the different conceptual frameworks that guide interventions. We describe the explanatory models and intervention approaches of two primary frameworks within MHPSS, which we label clinical and social-environmental. Using the examples of intimate partner violence and compromised parenting in humanitarian settings, we illustrate the complementarity of these two frameworks, as well as the challenges that can arise when either framework is inappropriately applied., Results: Clinical interventions prioritise the role of intrapersonal variables, biological and/or psychological, as mediators of change in the treatment of distress. Social-environmental interventions emphasise the role of social determinants of distress and target factors in the social and material environments in order to lower distress and increase resilience in the face of adversity. Both approaches play a critical role in humanitarian settings; however, the rationale for adopting one or the other approach is commonly insufficiently articulated and should be based on a thorough assessment of causal processes at multiple levels of the social ecology., Conclusions: Greater attention to the 'why' of our intervention choices and more explicit articulation of the causal models and theories of change that underlie those decisions (i.e., the 'how'), may strengthen intervention effects and minimise the risk of applying the inappropriate framework and actions to a particular problem.

The Pioneer and Voyager spacecraft made close-up measurements of Saturn's ionosphere and upper atmosphere in the 1970s and 1980s that suggested a chemical interaction between the rings and atmosphere. Exploring this interaction provides information on ring composition and the influence on Saturn's atmosphere from infalling material. The Cassini Ion Neutral Mass Spectrometer sampled in situ the region between the D ring and Saturn during the spacecraft's Grand Finale phase. We used these measurements to characterize the atmospheric structure and material influx from the rings. The atmospheric He/H 2 ratio is 10 to 16%. Volatile compounds from the rings (methane; carbon monoxide and/or molecular nitrogen), as well as larger organic-bearing grains, are flowing inward at a rate of 4800 to 45,000 kilograms per second., (Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Background: Gastric emptying is a complex physiological process regulating the division of a meal into smaller partitions for the small intestine. Disrupted gastric emptying contributes to digestive disease, yet current measures may not reflect different mechanisms by which the process can be altered., Methods: We have developed high temporal resolution solid and liquid gastric emptying breath tests in mice using [ 13 C]-octanoic acid and off axis- integrated cavity output spectroscopy (OA-ICOS). Stretched gamma variate and 2-component stretched gamma variate models fit measured breath excretion data., Key Results: These assays detect acceleration and delay using pharmacological (7.5 mg/kg atropine) or physiological (nutrients, cold exposure stress, diabetes) manipulations and remain stable over time. High temporal resolution resolved complex excretion curves with 2 components, which was more prevalent in mice with delayed gastric emptying following streptozotocin-induced diabetes. There were differences in the gastric emptying of Balb/c vs C57Bl6 mice, with slower gastric emptying and a greater occurrence of two-phase gastric emptying curves in the latter strain. Gastric emptying of C57Bl6 could be accelerated by halving the meal size, but with no effect on the occurrence of two-phase gastric emptying curves. A greater proportion of two-phase gastric emptying was induced in Balb/c mice with the administration of PYY (8-80 nmol) 60 min following meal ingestion., Conclusions and Inferences: Collectively, these results demonstrate the utility of high temporal resolution gastric emptying assays. Two-phase gastric emptying is more prevalent than previously reported, likely involves intestinal feedback, but contributes little to the overall rate of gastric emptying., (© 2018 John Wiley & Sons Ltd.)

Early research on the mental health of civilians displaced by armed conflict focused primarily on the direct effects of exposure to war-related violence and loss. Largely overlooked in this war exposure model were the powerful effects of ongoing stressors related to the experience of displacement itself. An ecological model of refugee distress is proposed, drawing on research demonstrating that mental health among refugees and asylum seekers stems not only from prior war exposure, but also from a host of ongoing stressors in their social ecology, or displacement-related stressors. Implications of this model for addressing the mental health and psychosocial needs of refugees and other displaced populations are considered.

Axons are living systems that display highly dynamic changes in stiffness, viscosity, and internal stress. However, the mechanistic origin of these phenomenological properties remains elusive. Here we establish a computational mechanics model that interprets cellular-level characteristics as emergent properties from molecular-level events. We create an axon model of discrete microtubules, which are connected to neighboring microtubules via discrete crosslinking mechanisms that obey a set of simple rules. We explore two types of mechanisms: passive and active crosslinking. Our passive and active simulations suggest that the stiffness and viscosity of the axon increase linearly with the crosslink density, and that both are highly sensitive to the crosslink detachment and reattachment times. Our model explains how active crosslinking with dynein motors generates internal stresses and actively drives axon elongation. We anticipate that our model will allow us to probe a wide variety of molecular phenomena-both in isolation and in interaction-to explore emergent cellular-level features under physiological and pathological conditions.

The Sample Analysis at Mars (SAM) instrument on board the Mars Science Laboratory Curiosity rover is designed to conduct inorganic and organic chemical analyses of the atmosphere and the surface regolith and rocks to help evaluate the past and present habitability potential of Mars at Gale Crater. Central to this task is the development of an inventory of any organic molecules present to elucidate processes associated with their origin, diagenesis, concentration, and long-term preservation. This will guide the future search for biosignatures. Here we report the definitive identification of chlorobenzene (150-300 parts per billion by weight (ppbw)) and C 2 to C 4 dichloroalkanes (up to 70 ppbw) with the SAM gas chromatograph mass spectrometer (GCMS) and detection of chlorobenzene in the direct evolved gas analysis (EGA) mode, in multiple portions of the fines from the Cumberland drill hole in the Sheepbed mudstone at Yellowknife Bay. When combined with GCMS and EGA data from multiple scooped and drilled samples, blank runs, and supporting laboratory analog studies, the elevated levels of chlorobenzene and the dichloroalkanes cannot be solely explained by instrument background sources known to be present in SAM. We conclude that these chlorinated hydrocarbons are the reaction products of Martian chlorine and organic carbon derived from Martian sources (e.g., igneous, hydrothermal, atmospheric, or biological) or exogenous sources such as meteorites, comets, or interplanetary dust particles., Key Points: First in situ evidence of nonterrestrial organics in Martian surface sediments Chlorinated hydrocarbons identified in the Sheepbed mudstone by SAM Organics preserved in sample exposed to ionizing radiation and oxidative condition.

H2O, CO2, SO2, O2, H2, H2S, HCl, chlorinated hydrocarbons, NO, and other trace gases were evolved during pyrolysis of two mudstone samples acquired by the Curiosity rover at Yellowknife Bay within Gale crater, Mars. H2O/OH-bearing phases included 2:1 phyllosilicate(s), bassanite, akaganeite, and amorphous materials. Thermal decomposition of carbonates and combustion of organic materials are candidate sources for the CO2. Concurrent evolution of O2 and chlorinated hydrocarbons suggests the presence of oxychlorine phase(s). Sulfides are likely sources for sulfur-bearing species. Higher abundances of chlorinated hydrocarbons in the mudstone compared with Rocknest windblown materials previously analyzed by Curiosity suggest that indigenous martian or meteoritic organic carbon sources may be preserved in the mudstone; however, the carbon source for the chlorinated hydrocarbons is not definitively of martian origin.

Objective: This case series examines the feasibility, specificity, and preliminary effectiveness of NeuroGame Therapy (NGT) for improving wrist control in four children with cerebral palsy (CP). NGT uses surface electromyographic (sEMG) signals routed through motivating computer games to improve motor control., Methods: Primary outcomes of NGT included feasibility (hours of play) and specificity (changes in sEMG activity during game play). Secondary outcomes included changes in co-contraction, range of motion, segmental alignment, and spontaneous upper extremity function following intervention., Results: Participants completed a mean of 8.8 hours of NGT over 5-6 weeks. Participants demonstrated dramatic improvement of the sEMG activity during game play. Several participants also showed improvements in range of motion, co-contraction, and spontaneous upper extremity function following NGT., Conclusion: This case series provides evidence for the feasibility, specificity, and effectiveness of NGT. Future studies will pair NGT with functional practice to improve transfer of learning to daily activities.

Samples from the Rocknest aeolian deposit were heated to ~835°C under helium flow and evolved gases analyzed by Curiosity's Sample Analysis at Mars instrument suite. H2O, SO2, CO2, and O2 were the major gases released. Water abundance (1.5 to 3 weight percent) and release temperature suggest that H2O is bound within an amorphous component of the sample. Decomposition of fine-grained Fe or Mg carbonate is the likely source of much of the evolved CO2. Evolved O2 is coincident with the release of Cl, suggesting that oxygen is produced from thermal decomposition of an oxychloride compound. Elevated δD values are consistent with recent atmospheric exchange. Carbon isotopes indicate multiple carbon sources in the fines. Several simple organic compounds were detected, but they are not definitively martian in origin.

Nerve growth factor (NGF) antagonism has long been proposed as a chronic pain treatment. In 2010, the FDA suspended clinical trials using tanezumab, a humanized monoclonal anti-NGF antibody, to treat osteoarthritis due to worsening joint damage in 16 patients. Increased physical activity in the absence of acute pain which normally prevents self-harm was purported as a potential cause. Such an adverse effect is consistent with an extension of tanezumab's primary mechanism of action by decreasing pain sensitivity below baseline levels. In animal inflammatory pain models, NGF antagonism decreases intraepidermal nerve fiber (IENF) density and attenuates increases in expression of nociception-related proteins, such as calcitonin gene-related peptide (CGRP) and substance P (SP). Little is known of the effects of NGF antagonism in noninflamed animals and the hypoalgesia that ensues. In the current study, we immunized rats with NGF or cytochrome C (cytC) and examined (1) nocifensive behaviors with thermal latencies, mechanical thresholds, the hot plate test, and the tail flick test, (2) IENF density, and (3) expression of CGRP, SP, voltage-gated sodium channel 1.8 (Nav1.8), and glutaminase in subpopulations of dorsal root ganglion (DRG) neurons separated by size and isolectin B4 (IB4) labeling. Rats with high anti-NGF titers had delayed responses on the hot plate test but no other behavioral abnormalities. Delayed hot plate responses correlated with lower IENF density. CGRP and SP expression was decreased principally in medium (400-800 μm(2)) and small neurons (<400 μm(2)), respectively, regardless of IB4 labeling. Expression of Nav1.8 was only decreased in small and medium IB4 negative neurons. NGF immunization appears to result in a more profound antagonism of NGF than tanezumab therapy, but we hypothesize that decreases in IENF density and nociception-related protein expression are potential mechanisms for tanezumab-induced hypoalgesia., (Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.)

There is clear evidence to support the use of pre-operative concurrent chemo-radiotherapy (CRT) in locally advanced rectal cancer. In the UK, most patients are selected for treatment if the resection margin is predicted to be involved. The selection criteria used includes primary tumours that threaten the resection margins on high-resolution pelvic MRI and low tumours requiring abdominoperineal excision. There is no consensus, however, to guide the treatment of patients who present with advanced rectal disease and synchronous, potentially resectable, metastatic disease. This case illustrates the potential risk of omitting radiation following a good response to neoadjuvant systemic chemotherapy.

Evidence of relaxation has appeared, for the first time, in the extremely high-beta, steady-state field-reversed configuration plasma states driven by rotating magnetic fields (RMF) in the translation, confinement, and sustainment experiment. The plasma self-organizes into a near-force-free state in the vicinity of the magnetic axis, with significant improvement in confinement. Associated with this change in magnetic topology is the appearance of an axial RMF component; this would, in turn, generate a current drive in the poloidal direction, thus sustaining the magnetic helicity. A newly developed two-dimensional "equilibrium-lite" model is employed to analyze the magnetic properties of the final high-confinement state, and shows a large q and a significant magnetic shear in the core.

An extremely high-beta (over 85%) self-organized field-reversed configuration (FRC) with a spherical-torus- (ST-)like core is produced in the translation, confinement, and sustainment experiment by highly super-Alfvénic translation of a spheromaklike plasmoid. Substantial flux conversion from toroidal into poloidal occurs during the capture process, resulting in the ST-like core. This plasma state exhibits a remarkable stabilizing property for the ubiquitous centrifugally driven interchange modes present in theta-pinch formed FRCs. This is explained, for the first time, by a simple model taking into account magnetic shear and centrifugal effects. The FRC-ST configuration has up to 4 times improvement in flux confinement times over the scaling of conventional theta-pinch formed FRCs and, thus, a significant improvement in the resistivity and transport.

Interchange modes have been a key limiting instability for many magnetic confinement fusion configurations. In previous studies intended to deal with these ubiquitous instabilities, complex, transport enhancing, minimum-B producing coils were added to the otherwise simple linear mirror plasma. Possible solutions for returning to a simple symmetric mirror configuration, such as ponderomotive fields, are weak and difficult to apply. A new method is demonstrated here for the first time, utilizing rotating magnetic fields that are simple to apply and highly effective. A simple and easily comprehensible theory has also been developed to explain the remarkable stabilizing properties. Although this work has been performed on field reversed configurations, it should have a wide application to other confinement schemes, and could become a cornerstone for high-beta plasma stability.

Information processing in the inferior colliculus depends on interactions between ascending pathways and intrinsic circuitry, both of which exist within a functional tonotopic organization. To determine how local projections of neurons in the inferior colliculus are related to tonotopy, we placed a small iontophoretic injection of biodextran amine at a physiologically characterized location in the inferior colliculus. We then used electrophysiological recording to place a grid of small deposits of Chicago Sky Blue throughout the same frequency range to specify an isofrequency contour. Using three-dimensional computer reconstructions, we analyzed patterns of transport relative to the physiologically determined isofrequency contour to quantify the extent of the intrinsic connection lamina in all three dimensions. We also performed a quantitative analysis of the numbers of cells in different regions relative to the biodextran amine injection. Biodextran amine-labeled fibers were mainly located dorsomedial to the injection site, confined within the isofrequency contour, but biodextran amine-labeled cells were mainly located ventrolateral to the injection site. When we counted numbers of labeled cells classified by morphological type, we found that both elongate and multipolar cells were labeled within the isofrequency contour. Because the dendrites of multipolar cells typically extend outside the isofrequency lamina, it is likely that they receive input from other isofrequency contours and relay it to more dorsomedial portions of their specific isofrequency contour, along with the frequency-specific projections of the elongate cells. Within a given isofrequency contour, there is a consistent organization in which intrinsic connections ascend from the ventrolateral portion to more dorsomedial points along the contour, forming a cascaded system of intrinsic feedforward connections that seem ideally suited to provide the delay lines necessary to produce several forms of selectivity for temporal patterns in inferior colliculus neurons.

A number of studies have implicated the interactions of the excitatory amino acid L-glutamate (Glu) with its ionotropic and metabotropic receptors as important components of the mechanism underlying the dopaminergic neurotoxicity of 1-methyl-4-phenylpyridinium [MPP(+)]. Furthermore, microdialysis experiments have demonstrated that perfusion of relatively high concentrations of MPP(+) into the rat striatum evoke a delayed, massive release of Glu. Interestingly, perfusion of MPP(+) also mediates a similar release of glutathione (GSH). Together, these observations raise the possibility that the rise of extracellular Glu mediated by MPP(+) may be the result of hydrolysis of released GSH by gamma-glutamyl transpeptidase (gamma-GT). In the present investigation it is demonstrated that perfusions of solutions of 0.7 and 1.3 mM MPP(+) dissolved in artificial cerebrospinal fluid into the rat striatum evoke neurotoxic damage to dopaminergic terminals, assessed by both a two-day test/challenge procedure and tyrosine hydroxylase immunoreactivity, but without the release of Glu. Perfusions of 2.5 mM MPP(+) cause more extensive dopaminergic neurotoxicity and a dose-dependent release of Glu. However, neither this release of Glu nor MPP(+)-induced dopaminergic neurotoxicity are blocked by the irreversible gamma-GT inhibitor acivicin. Together, these observations indicate that a rise of extracellular levels of Glu is not essential for the dopaminergic neurotoxicity of MPP(+). Furthermore, the rise of extracellular Glu caused by perfusion of 2.5 mM MPP(+) is not the result of the gamma-GT-mediated hydrolysis of released GSH. It is possible that the rise of extracellular levels of Glu, L-aspartate, L-glycine and L-taurine evoked by perfusions of 2.5 mM MPP(+) into the rat striatum may reflect, at least in part, the release of these amino acids from astrocytes.

High-beta plasmoids can survive the violent dynamics of supersonic reflection off mirror structures, producing a stable high-beta field-reversed configuration (FRC). This shows both the robustness of FRCs and their tendency to assume a preferred plasma state, possibly conforming to a relaxation principle. The key observations are (1) approximate preservation of the magnetic helicity, (2) substantial conversion from toroidal to poloidal magnetic flux, (3) substantial toroidal flow, and (4) a high-beta quiescent final state. These results are from the Translation, Confinement, and Sustainment experiment where a disorganized plasmoid is injected at super-Alfvenic speed into a confinement chamber. After successive reflections from end mirrors, the plasmoid settled into a near-FRC state with high beta and low toroidal magnetic field. The flux conversion and helicity preservation are inferred by an interpretive model.

In the United States today, the use of tobacco has become an entrenched part of teenage culture. The present study used the 1997 Youth Risk Behavior Survey (YRBS), which collected data from a nationally representative sample of 16,262 students in public and private high schools, to compare the tobacco use patterns of athletes and nonathletes. The independent variable, athletic participation, differentiated between moderately involved (1 or 2 teams) and highly involved (3 or more teams) athletes. Frequency of cigarette and cigar smoking and smokeless tobacco use served as the operational measure of tobacco use. Age, race/ethnicity, parental education, and residence were controlled. Logistic regression was used to calculate odds ratios for female and male athletes and nonathletes for each of the tobacco use variables. It was found that both male and female athletes were less likely to have ever smoked regularly, the effect being stronger for more highly involved athletes of both genders. Cigar smoking was unrelated to athlete status. Both female and male athletes were more likely to have used smokeless tobacco, the effect being stronger for more highly involved athletes of both genders. The findings are discussed in terms of access to health information, performance considerations, social status factors, the salience of an athletic identity, and the influence of the athletic subculture on its members.

Effective pain management in the terminally ill patient requires an understanding of pain control strategies. Ongoing assessment of pain is crucial and can be accomplished using various forms and scales. It is also important to determine if the pain is nociceptive (somatic or visceral pain) or neuropathic (continuous dysesthesias or chronic lancinating or paroxysmal pain). Nociceptive pain can usually be controlled with nonsteroidal antiinflammatory drugs or corticosteroids, whereas neuropathic pain responds to tricyclic antidepressants or anticonvulsants. Relief of breakthrough pain requires the administration of an immediate-release analgesic medication. If a significant amount of medication for breakthrough pain is already being given, the baseline dose of sustained-release analgesic medication should be increased. If pain does not respond to one analgesic medication, physicians should use an equianalgesic dose chart when changing the medication or route of administration. Opioid rotation can be used if pain can no longer be controlled on a specific regimen. The impact of unresolved psychosocial or spiritual issues on pain management may need to be addressed.

A new method for the separation of denatured alpha-, beta- and kappa- caseins by hydrophobic interaction chromatography (HIC) is proposed. The method is based on an easy solubilization of commercial and real samples by 4.0 M guanidine thiocyanate (GdmSCN) and elution on a TSK-Gel(R) Phenyl-5PW column (TosoHaas) in the presence of 8.0 M urea in the mobile phase. The procedure, applied to commercial caseins and to real, raw samples (whole milk powder and fat-free yoghurt) is not expensive, it requires common high performance liquid chromatography (HPLC) instrumentation and allows the separation of caseins also in the presence of whey proteins. Quantitative results on the analysis of alpha-, beta- and kappa-caseins in real samples are also reported.

Electrical stimulation of vagal afferents or cardiopulmonary sympathetic afferent fibers excites C(1)--C(2) spinal neurons. The purposes of this study were to compare the responses of superficial (depth <0.35 mm) and deeper C(1)--C(2) spinal neurons to noxious chemical stimulation of cardiac afferents and determine the relative contribution of vagal and sympathetic afferent pathways for transmission of noxious cardiac afferent input to C(1)--C(2) neurons. Extracellular potentials of single C(1)--C(2) neurons were recorded in pentobarbital anesthetized and paralyzed male rats. A catheter was placed in the pericardial sac to administer a mixture of algogenic chemicals (0.2 ml) that contained adenosine (10(-3) M), bradykinin, histamine, serotonin, and prostaglandin E(2) (10(-5) M each). Intrapericardial chemicals changed the activity of 20/106 (19%) C(1)--C(2) spinal neurons in the superficial laminae, whereas 76/147 (52%) deeper neurons responded to cardiac noxious input (P < 0.01). Of 96 neurons responsive to cardiac inputs, 48 (50%) were excited (E), 41 (43%) were inhibited (I), and 7 were excited/inhibited (E-I) by intrapericardial chemicals. E or I neurons responsive to intrapericardial chemicals were subdivided into two groups: short-lasting (SL) and long-lasting (LL) response patterns. In superficial gray matter, excitatory responses to cardiac inputs were more likely to be LL-E than SL-E neurons. Mechanical stimulation of the somatic field from the head, neck, and shoulder areas excited 85 of 95 (89%) C(1)--C(2) spinal neurons that responded to intrapericardial chemicals; 31 neurons were classified as wide dynamic range, 49 were high threshold, 5 responded only to joint movement, and no neuron was classified as low threshold. For superficial neurons, 53% had small somatic fields and 21% had bilateral fields. In contrast, 31% of the deeper neurons had small somatic fields and 46% had bilateral fields. Ipsilateral cervical vagotomy interrupted cardiac noxious input to 8/30 (6 E, 2 I) neurons; sequential transection of the contralateral cervical vagus nerve (bilateral vagotomy) eliminated the responses to intrapericardial chemicals in 4/22 (3 E, 1 I) neurons. Spinal transection at C(6)--C(7) segments to interrupt effects of sympathetic afferent input abolished responses to cardiac input in 10/10 (7 E, 3 I) neurons that still responded after bilateral vagotomy. Results of this study support the concept that C(1)-C(2) superficial and deeper spinal neurons play a role in integrating cardiac noxious inputs that travel in both the cervical vagal and/or thoracic sympathetic afferent nerves.

Backbone dynamics of homodimeric apo-S100B were studied by (15)N nuclear magnetic resonance relaxation at 9.4 and 14.1 T. Longitudinal relaxation (T(1)), transverse relaxation (T(2)), and the (15)N-[(1)H] NOE were measured for 80 of 91 backbone amide groups. Internal motional parameters were determined from the relaxation data using the model-free formalism while accounting for diffusion anisotropy. Rotational diffusion of the symmetric homodimer has moderate but statistically significant prolate axial anisotropy (D( parallel)/D( perpendicular) = 1.15 +/- 0.02), a global correlation time of tau(m) = 7.80 +/- 0.03 ns, and a unique axis in the plane normal to the molecular symmetry axis. Of 29 residues at the dimer interface (helices 1 and 4), only one has measurable internal motion (Q71), and the order parameters of the remaining 28 were the highest in the protein (S(2) = 0.80 to 0.91). Order parameters in the typical EF hand calcium-binding loop (S(2) = 0.73 to 0.87) were slightly lower than in the pseudo-EF hand (S(2) = 0.75 to 0.89), and effective internal correlation times, tau(e), distinct from global tumbling, were detected in the calcium-binding loops. Helix 3, which undergoes a large, calcium-induced conformational change necessary for target-protein binding, does not show evidence of interchanging between the apo and Ca(2+)-bound orientations in the absence of calcium but has rapid motion in several residues throughout the helix (S(2) = 0.78 to 0.88; 10 < or = tau(e) < or = 30 ps). The lowest order parameters were found in the C-terminal tail (S(2) = 0.62 to 0.83). Large values for chemical exchange also occur in this loop and in regions nearby in space to the highly mobile C-terminal loop, consistent with exchange broadening effects observed.

The amino acid taurine serves many functions in the nervous system serving as inhibitory neurotransmitter/neuromodulator, neurotrophin, antioxidant, and osmolyte. Taurine levels are increased following brain injury and glucocorticoid administration. Thus, the purpose of this study was to examine spinal taurine concentrations following spinal cord injury (SCI) and methylprednisolone (MP) treatment of SCI. A total of 44 adult male Sprague-Dawley rats were divided into control and lesion groups. Control rats received a T6 vertebral laminectomy while lesioned rats received a laminectomy followed by complete spinal transection. Half of the animals in each group received MP intravenously following sham-operation or SCI. Rats survived for 7 or 30 days and concentrations of taurine in spinal gray and white matter, in spinal segments both near and distant from the injury epicenter, were resolved by HPLC analysis. Taurine levels were increased 7 and 30 days following transection in spinal segments immediately adjacent to the lesion and were further elevated by MP treatment. No increases were seen in far rostral/caudal segments, and MP treatment alone had no effect on spinal taurine levels. These findings demonstrate that spinal injury results in increased taurine concentrations in spinal segments undergoing the greatest degree of cellular reactivity and tissue reorganization and that MP therapy potentiates these increases. These findings are significant in that they further characterize the effects of acute MP therapy in spinal tissue. Since taurine is thought to be involved in neuroprotection and/or regeneration following injury, the potentiation of taurine levels by MP treatment may relate to its therapeutic properties.

The glial enzyme glutamine synthetase (GS) is critical for central nervous system catabolism of glutamate and glutamine production. Upregulation of GS is a hallmark of reactive astrocytosis, although such induction following spinal cord injury (SCI) has not been reported. This study's purpose was to determine if GS activity is increased following SCI. Experimental rats received a complete spinal transection at the T5 segment and control rats received a laminectomy only. GS activities were determined using an enzymatic microassay. Glutamine levels were resolved in semi-adjacent sections. At 7 days following SCI, GS activity increased an average of 170-190% in white matter and 15-25% in gray matter immediately adjacent to the transection, and 70-90% in white matter and 40-45% in gray matter from cervical and lumbar enlargements. Correlative increases in glutamine were observed also. These findings further characterize the astrocytic response to SCI, which may contribute to altered glutamine metabolism in injured spinal tissue.

The use of drops in chemical analysis methodology and instrumentation has a deeply rooted past in the area of electrochemistry through the evolution of the dropping mercury electrode (DME). This history has also been deeply rooted in the field of surface science due to the inextricable connection between surface tension forces and drop formation. While the use of the DME is well established, the evolution of drop-based analytical measurements using aqueous and/or organic drops is a rapidly emerging and diverse field, encompassing several interdisciplinary areas of science: surface science and interfacial surface tension phenomena, spectroscopic detection, analytical instrumentation hyphenation, liquid membrane separation, reagent chemistry, electrochemistry, and so on. This review of 112 references covers various aspects of drop-based analytical measurements involving aqueous and/or organic drops. The review is divided into four sections, although the classification of a particular reference into a given section can sometimes be argued. The first section considers the use of drops as a detector component. The second section deals with fundamental studies that probe drop-related chemical and physical phenomena that are relevant to current and future developments in analytical chemistry. The next section covers recent advances in the area of microfluidic sample handling and instrumentation hyphenation. The final section reports upon emerging technologies aimed toward drop-based chemical analyzers that incorporate a number of steps in a chemical analysis: microextraction, preconcentration, reagent chemistry, microfluidic handling, and detection.

The number of persons 65 years of age and older continues to increase dramatically in the United States. Comprehensive health maintenance screening of this population is becoming an important task for primary care physicians. As outlined by the U.S. Preventive Services Task Force, assessment categories unique to elderly patients include sensory perception and injury prevention. Geriatric patients are at higher risk of falling for a number of reasons, including postural hypotension, balance or gait impairment, polypharmacy (more than three prescription medications) and use of sedative-hypnotic medications. Interventional areas that are common to other age groups but have special implications for older patients include immunizations, diet and exercise, and sexuality. Cognitive ability and mental health issues should also be evaluated within the context of the individual patient's social situation-not by screening all patients but by being alert to the occurrence of any change in mental function. Using an organized approach to the varied aspects of geriatric health, primary care physicians can improve the care that they provide for their older patients.

Myosin II and V are important for the generation and segregation of subcellular compartments. We observed that vesicular myosin II and V were associated with the protein scaffolding of a common subset of vesicles by density sedimentation, electron microscopy, and immunofluorescence. Solubilization of either myosin II or V was caused by polyphosphates with the following efficacy at 10 mM: for myosin II ATP-Mg(2+) = ATP = AMP-PNP (5'-adenylyl imidodiphosphate) > pyrophosphate = tripolyphosphate > tetrapolyphosphate = ADP > cAMP = Mg(2+); and for myosin V pyrophosphate = tripolyphosphate > ATP-Mg(2+) = ATP = AMP-PNP > ADP = tetrapolyphosphate > cAMP = Mg(2+). Consequently, we suggest solubilization was not an effect of phosphorylation, hydrolysis, or disassociation of myosin from actin filaments. Scatchard analysis of myosin V binding to stripped dense vesicles showed saturable binding with a K(m) of 10 nM. Analysis of native vesicles indicates that these sites are fully occupied. Together, these data show there are over 100 myosin Vs/vesicle (100-nm radius). We propose that polyphosphate anions bind to myosin II and V and induce a conformational change that disrupts binding to a receptor.

The Centers for Disease Control and Prevention updated its guidelines for the treatment of sexually transmitted diseases. The guidelines include the following information: recommendations for hepatitis A immunization and expanded indications for hepatitis B vaccination; updated diagnostic criteria for pelvic inflammatory disease and parenteral treatment regimens; information on two additional antiviral agents for the treatment of genital herpes; a recommendation for use of a single 1-g dose of azithromycin (Zithromax) to treat urethritis and chlamydial cervicitis; information on the use of quinolones in the treatment of gonococcal infections; information on podofilox and imiquimod, which are both patient-applied medications, in the treatment of noncervical human papillomavirus infection; updated guidelines for the prevention and detection of congenital syphilis; and information on how to prevent the spread of sexually transmitted diseases by educating patients about the importance of changing their sexual behaviors. To have a significant impact on the current rate of transmission of sexually transmitted diseases, family physicians should develop a plan to integrate the guidelines into their practices.

First, a novel technique for calibration of a dynamic surface tension detector (DSTD) is described. The DSTD measures the differential pressure as a function of time across the liquid-air interface of growing drops that repeatedly form and detach at the end of a capillary tip. The calibration technique utilizes the ratio of pressure signals acquired from the drop growth of two separate solutions, i.e. a standard solution and a corresponding mobile phase, such as water, both of which have a known surface tension. Once calibrated, the dynamic surface tension of an analyte is obtained from the ratio of the pressure signals from the analyte solution to that of the mobile phase solution. Thus, this calibration technique eliminates the need to optically image the radius of the expanding drop of liquid. Accurate dynamic surface tension determinations were achieved for aqueous sodium dodecyl sulfate (SDS) solutions over a concentration range of 0.5-5.4 mM. The measured surface tensions for these SDS solutions range from 70.3 to 46.8 dyne/cm and were in excellent agreement with the literature. A precision of 0.2 dyne/cm (1 S.D.) was routinely obtained. Second, the DSTD with this calibration technique was combined with flow injection analysis (FIA) for the study of model protein solutions and polymer solutions. The kinetic surface tension behavior of aqueous bovine serum albumin (BSA) solutions as a function of concentration and flow rate is presented. Evaluation of the dynamic surface tension data illustrates that a protein such as BSA initially exhibits kinetically-hindered surface tension lowering, i.e. a time dependence, as BSA interacts with the liquid-air interface of an expanding drop. FIA/DSTD is then shown to be an effective tool for the rapid study of kinetically-hindered surfactant mixtures. It was found that mixtures of SDS and the polymeric surfactant Brij(R)-35 (lauryl polyoxyethylene ether with an average molecular weight of 1200 g/mol) result in essentially an additive lowering of the surface tension. Mixtures of polyethylene glycol (PEG), with an average molecular weight of 1470 g/mol, and Brij(R)-35, however, result in a competitive (non-additive) surface tension with the Brij(R)-35 dominating the response.

We have shown that stimulation of cardiopulmonary sympathetic afferent fibers activates relays in upper cervical segments to suppress activity of lumbosacral spinal cells. The purpose of this study was to determine if chemical excitation (glutamate) of upper cervical cell bodies changes the spontaneous activity and evoked responses of lumbosacral spinal cells to colorectal distension (CRD). Extracellular potentials were recorded in pentobarbital-anesthetized male rats. CRD (80 mmHg) was produced by inflating a balloon inserted in the descending colon and rectum. A total of 135 cells in the lumbosacral segments (L(6)-S(2)) were activated by CRD. Seventy-five percent (95/126) of tested cells received convergent somatic input from the scrotum, perianal region, hindlimb, and tail; 99/135 (73%) cells were excited or excited/inhibited by CRD; and 36 (27%) cells were inhibited or inhibited/excited by CRD. A glutamate (1 M) pledget placed on the surface of C(1)-C(2) segments decreased spontaneous activity and excitatory CRD responses of 33/56 cells and increased spontaneous activity of 13/19 cells inhibited by CRD. Glutamate applied to C(6)-C(7) segments decreased activity of 10/18 cells excited by CRD, and 9 of these also were inhibited by glutamate at C(1)-C(2) segments. Glutamate at C(6)-C(7) increased activity of 4/6 cells inhibited by CRD and excited by glutamate at C(1)-C(2) segments. After transection at rostral C(1) segment, glutamate at C(1)-C(2) still reduced excitatory responses of 7/10 cells. Further, inhibitory effects of C(6)-C(7) glutamate on excitatory responses to CRD still occurred after rostral C(1) transection but were abolished after a rostral C(6) transection in 4/4 cells. These data showed that C(1)-C(2) cells activated with glutamate primarily produced inhibition of evoked responses to visceral stimulation of lumbosacral spinal cells. Inhibition resulting from activation of cells in C(6)-C(7) segments required connections in the upper cervical segments. These results provide evidence that upper cervical cells integrate information that modulates activity of distant spinal neurons responding to visceral input.

Intraocular co-grafts of rat fetal spinal cord and dorsal root ganglia were used to examine the enhanced survival, growth, and differentiation of sensory neurons by nerve growth factor. E14 lumbar spinal segments were implanted into the anterior eye chamber of capsaicin-pretreated rats. Two weeks later, an E14 dorsal root ganglion was implanted beside the spinal cord graft. Nerve growth factor or vehicle was injected weekly for 4 weeks into the anterior eye chamber. Co-grafts were examined weekly and, at 6 weeks, processed for calcitonin gene-related peptide (CGRP) immunofluorescence. No differences in overall size were determined for the grafts. Co-grafts treated with nerve growth factor contained many more CGRP neurons (19.4 cells/20 microm) that were significantly larger (mean 764 microm2) than neurons from control co-grafts (8.6 cells/20 microm; mean 373 microm2). In co-grafts treated with nerve growth factor, CGRP-immunoreactive fibers were extensive in the dorsal root ganglion, adjacent iris, and spinal cord compared to control co-grafts. A few CGRP-positive motoneurons were observed in the spinal cord, but no differences in number or size of motoneurons were found. The current report demonstrates that spinal cord and dorsal root ganglia can be co-grafted in oculo for long periods of time. Many dorsal root ganglion neurons survive and send peripheral processes into the iris and central processes into the spinal cord under the influence of exogenous nerve growth factor. The intraocular graft paradigm can be of use to further examine the role of neurotrophic factors in regulating or modulating dorsal root ganglion and spinal cord neurons.

Outpatient detoxification of patients with alcohol or other drug addiction is being increasingly undertaken. This type of management is appropriate for patients in stage I or stage II of withdrawal who have no significant comorbid conditions and have a support person willing to monitor their progress. Adequate dosages of appropriate substitute medications are important for successful detoxification. In addition, comorbid psychiatric, personality and medical disorders must be managed, and social and environmental concerns need to be addressed. By providing supportive, nonjudgmental, yet assertive care, the family physician can facilitate the best possible chance for a patient's successful recovery.

Purpose: To determine whether high school athletic participation among adolescents in Western New York was associated with reduced rates of sexual behavior and pregnancy involvement., Methods: A secondary analysis of data from the Family and Adolescent Study, a longitudinal study of a random sample of adolescents (ages 13-16 years) from 699 families living in households in Western New York. A general population sample was obtained with characteristics closely matching the census distributions in the area. Interview and survey methods provided data on athletic participation, frequency of sexual relations during the past year, and risk for pregnancy. Bivariate correlations were used to examine relationships among athletic participation, demographic and control variables, and measures of sexual behavior and pregnancy rates. Next, path analyses were done in order to test for hypothesized relationships between athletic participation, sexual behavior, and pregnancy involvement while controlling for age, race, income, family cohesion, and non-athletic forms of extracurricular activity. Variables that were significantly associated with sexual behavior and/or pregnancy involvement were presented for both sexes within the resulting multivariate models., Results: Lower income and higher rates of sexual activity were associated with higher rates of pregnancy involvement for both sexes. Family cohesion was associated with lower sexual activity rates for both sexes. For girls, athletic participation was directly related to reduced frequency of sexual behavior and, indirectly, to pregnancy risk. Male athletes did not exhibit lower rates of sexual behavior and involvement with pregnancy than male non-athletes. Boys who participated in the arts, however, did report lower rates of sexual behavior and, indirectly, less involvement with pregnancy., Conclusions: Female adolescents who participated in sports were less likely than their non-athletic peers to engage in sexual activity and/or report a pregnancy. Among male adolescents, athletic participation was unrelated to sexual behavior and pregnancy involvement. Teen pregnancy prevention efforts for girls should consider utilizing sport as a strategic tool.

Isometric contractions and force-frequency relationships (FFR) were assessed in isolated ventricular preparations of 3- and 4-day chick embryos (EM) and posthatched (PH) chicks. Pacing protocols for the FFR assessment were applied in normal buffer, buffer with 50% and 25% of normal Na+ concentration, and in buffer with ryanodine. PH myocardium showed greater peak force and more prominent FFR than EM. 50% low Na+ superfusion induced positive inotropic effect and increase in the FFR in PH and EM. 25% low Na+ superfusion induced negative inotropic effect and suppressed FFR more prominent in EM. Ryanodine more suppressed FFR in PH myocardium. The observed age-dependent differences substantiate the fact that Na-Ca exchange plays a leading role in the FFR regulation in early embryonic myocardium and sarcoplasmic reticulum plays a leading role in PH myocardium.

Physiological studies indicate that neurons in the upper cervical spinal cord have descending projections to the lumbosacral spinal cord and mediate inhibition of dorsal horn neurons activated from afferent input. In the present study, retrograde tracing techniques were used to examine the distribution of propriospinal neurons in C1-C2 spinal segments that project to lumbosacral spinal segments. Fluorogold or horseradish peroxidase were injected unilaterally or bilaterally into the L5-S1 spinal segments. After 2-4 days, rats were perfused with fixative and C1-C2 spinal segments were processed for retrograde labeling. Numerous neurons were found in the C1-C2 segments. In unilaterally and bilaterally injected rats, retrogradely labeled neurons were located on both the ipsilateral and contralateral sides. Retrogradely labeled neurons were located in the following locations: lateral cervical and spinal nuclei, nucleus proprius, ventral horn and the central gray region (area X). These studies demonstrate a descending projection from C1-C2 segments to the lower lumbar and sacral spinal cord. We hypothesize that many of these C1-C2 propriospinal neurons are important in modulating responses of spinal neurons at lower segmental levels to various peripheral stimuli.

Members of arrestin/beta-arrestin protein family are thought to participate in agonist-mediated desensitization of G-protein-coupled receptors, including rhodopsin and beta2-adrenergic receptor. Unlike in human and cow, splice variants of this protein family in rat have not been studied extensively, and there has been no report on their existence at protein level. Hence, a previous report by others on the localization of both beta-arrestin-1 and -2 in a wide range of innervated rat tissues could imply their broad receptor specificity. In this report we show the presence of two alternatively spliced forms of beta-arrestin-1 in several rat tissues using both reverse transcription-polymerase chain reaction and Western immunoblot. Splicing of beta-arrestin-1 pre-mRNA appears to be subject to differential regulation between the rat CNS and peripheral tissues. In contrast, we detected no splice variants of beta-arrestin-2 in rat. A comparison of the genomic DNA sequences of bovine and rat beta-arrestin-2, where the splicing of bovine beta-arrestin-2 mRNA has been reported, revealed a high degree of homology in their organization of exons and introns as well as certain differences that might be responsible for the different processing of beta-arrestin-2 mRNA in the two species. Our two-dimensional isoelectric focusing gels using rat spinal cord and heart tissues demonstrate isoelectric heterogeneity of rat beta-arrestin-1, suggesting that beta-arrestin-1 is subject to post-translational modification unlike beta-arrestin-2.

The descending serotonergic system provides a powerful inhibitory input to the dorsal horn of the spinal cord. Little is known about the chemical identity of the spinal neurons that the serotonergic system innervates, although spinal enkephalinergic neurons are likely candidates. This study investigated the apposition of serotonin-immunoreactive varicosities onto enkephalin- and neurotensin-immunoreactive neurons in the rat lumbosacral spinal cord. Using a double immunofluorescence technique, serotonin-immunoreactive varicosities were observed to abut the soma or proximal dendrites of [Met]enkephalin- and neurotensin-immunoreactive neurons. Nearly 75% of all [Met]enkephalin- and neurotensin-immunoreactive neurons were apposed by serotonin-immunoreactive varicosities in the marginal zone and dorsal gray commissure. In substantia gelatinosa, approximately half of the [Met]enkephalin- and neurotensin-immunoreactive neurons were juxtaposed by serotonin-immunoreactive varicosities. [Met]enkephalin-immunoreactive neurons also were bordered by serotonin-immunoreactive varicosities in the nucleus proprius (65%) and sacral parasympathetic nucleus (75%). The results of this study suggest that the descending serotonergic system mediates nociception via probable contacts with intrinsic enkephalin and neurotensin spinal systems. The mode of action of spinal serotonin on enkephalin and neurotensin neurons may be through "volume" transmission vs synaptic or "wiring" transmission.

Using multivariate analysis of covariance to test hypotheses about the effects of sports and sexual behavior on a sample of 611 Western New York adolescents, this study concludes that athletic participation and gender interact to influence adolescent sexual outcomes. Female athletes report significantly lower rates of sexual activity than female nonathletes; male athletes report slightly (though not significantly) higher rates than male nonathletes. The gender-specific effect of sports on sexual behavior remains, net of the impacts of race, age, socioeconomic status, quality of family relations, and participation in other extracurricular activities. This paper introduces cultural resource theory to explain how athletic participation influences both traditional cultural scripts and exchange resources, which, in turn, condition the sexual bargaining process and its outcomes for adolescents.

Retrograde, transneuronal tracing with Bartha's strain of pseudorabies virus was used in rats to identify spinal cord, brainstem and hypothalamic loci of uterine-related neurons that could function in the regulation of uterine activity. Based on the premise that estrogen might influence such uterine-related neurons, the existence of estrogen receptors in neurons in these same loci was examined. Viral injections were made into the uterine cervix, body and cervical end of the uterine horns, and the rats allowed to survive for four to six days. After four days, mainly the spinal cord, medulla and pons contained virus-infected neurons. After longer survival times, progressively higher levels of the neuraxis contained viral-labeled neurons, so that by six days hypothalamic uterine-related neurons were identified. First-order virus-infected neurons were visualized by immunohistochemistry in the pelvic paracervical parasympathetic ganglia and in inferior mesenteric sympathetic ganglia. Preganglionic and putative interneurons were labeled in the lumbosacral spinal cord and thoracic spinal cord mainly in the lateral horn area (sacral parasympathetic nucleus and intermediolateral nucleus), lateral aspect of the dorsal horn, intermediate gray, lamina X and dorsal gray commissural area. In the brainstem, labeling was most evident and consistent in the nucleus tractus solitarius, ventrolateral medulla, raphe magnus and pallidus nuclei, parapyramidal area, A5 cell group, Barrington's nucleus of the pons and periaqueductal gray of the midbrain. In the hypothalamus, virus-infected neurons were most marked in the paraventricular nucleus, with fewer in the medial preoptic area and ventromedial hypothalamic nucleus. Estrogen receptor-immunoreactive neurons were most often present among the virus-labeled uterine-related neurons of the spinal cord, nucleus tractus solitarius, ventrolateral medulla, periaqueductal gray, medial preoptic area and ventromedial hypothalamic nucleus. These results identify a multisynaptic pathway of neurons whose eventual output is involved in uterine functions, whose distribution is similar to that revealed by pseudorabies virus tracing from other visceral organs, and which are often mixed among estrogen-responsive neurons.

The purpose of this study was to assess the functional outcomes of first-time cerebrovascular accident survivors 1 to 5 years after rehabilitation. Subjects (n=68) consisted of individuals discharged from a regional rehabilitation center between 1992 and 1996 with the diagnosis of first-time cerebrovascular accident. The Adult Functional Independence Measure (FIM), an on-site outcomes measurement tool, was used to assess subjects' admittance and discharge total FIM scores. The Adult Functional Independence Measure, a phone interview methodology, was used to assess individuals' functional levels from 1 through 5 years after discharge from rehabilitation. Motor (Rasch Motor) and cognitive (Rasch Cognitive) components of the FIM also were analyzed over time. Data pertaining to differences in function between genders, site of lesion, family support, and whether therapy was received after discharge were collected. Data were analyzed to determine changes in function over time. Significant increases in total FIM and motor and cognitive scores occurred between admittance and discharge and between discharge and 1 year after discharge. Although not significant, slight increases were noted in all three measures up to 3 years after discharge. From 3 to 5 years after discharge, a steady decline was noted. First-time cerebrovascular accident survivors who did not experience additional medical problems continued to improve during the first 3 years after discharge from a rehabilitation center. After this time, however, declines were noted in total FIM, Rasch Motor, and Rasch Cognitive scores.

The class III antiarrhythmic agent, azimilide, has been shown to inhibit dihydroalprenolol binding to the beta-adrenergic receptor of rat brain and heart in an in-vitro ligand-binding assay. Azimilide, was assessed for beta-adrenergic activity, either agonist or antagonist, in the isolated perfused guinea pig heart in comparison with class III reference agents and the class II agent, propranolol. Varying concentrations of compound (0.03-100 microM) were retrogradely perfused and the effects on corrected QT interval, baseline heart rate, and isoproterenol-stimulated heart rate were measured. Propranolol, dl-sotalol, azimilide, and d-sotalol inhibited isoproterenol-induced tachycardia with IC50 values (the concentration giving 50% inhibition of isoproterenol-stimulated heart rate) of 0.12, 1.4, 14.6, and 38.0 microM, respectively. Clofilium, dofetilide, and sematilide did not affect the action of isoproterenol. Dofetilide, clofilium, azimilide, sematilide, dl-sotalol, and d-sotalol increased the QTc interval approximately 20 ms at concentrations of 0.1, 0.3, 1.0, 3.0, 30.0, and 100.0 microM, respectively. The class III antiarrhythmic agents also slowed baseline heart rate and exhibited linear R-R and QT-interval relationships of similar slope. Azimilide's antagonism of isoproterenol in this isolated heart model may reflect a direct receptor interaction or a contribution from the bradycardic action of the compound, which distinguishes it from several other pure IKr-blocking class III antiarrhythmic agents.

Ganglion cysts are commonly seen in orthopedic and general practice. Compression of the common peroneal nerve by a ganglion cyst is rare in children; to the authors' knowledge, only five cases in patients younger than 18 years have been reported. A ganglion cyst was found in a 3-year-old child who was brought in for an evaluation of intoeing and was found subsequently to have a mass in the proximal aspect of the right leg. The literature is reviewed with attention to specific recommendations for the evaluation of soft tissue masses and the utility of imaging modalities.

Effects of electrically stimulating the left stellate ganglion to activate cardiopulmonary sympathetic afferent (CPSA) fibers were determined on C1-C3 dorsal horn neurons in anaesthetized rats. Fifty-two of 53 dorsal horn neurons affected by CPSA stimulation were excited and one neuron was inhibited. In 6 experiments, dorsal columns and ventrolateral funiculi were sequentially lesioned to determine neuronal pathways involved in CPSA activation of C1-C3 neurons. In 6 additional experiments, spinal transection at rostral C1 was used to determine the contribution of supraspinal relays. We concluded that CPSA input to C1-C3 segments travelled bilaterally in ventrolateral pathways, and that supraspinal relays were not required for CPSA excitation of C1-C3 neurons. These results suggest that neurons in C1-C3 segments might play an important role in processing visceral spinal afferent information.

A reliable serum assay that can discriminate between cardiac and skeletal muscle injury is not available for diagnostic use in laboratory animals. We tested and supported the hypotheses that serum cardiac troponin T (cTnT) was widely applicable in laboratory animals as a biomarker of cardiac injury arising from various causes; that it increased in proportion to severity of cardiac injury; and that it was more cardiospecific than creatine kinase (CK) or lactate dehydrogenase (LD) isozyme activities. In canine and rat models of myocardial infarction, cTnT concentration increased 1,000- to 10,000-fold and was highly correlated with infarct size within 3 h of injury. Serum CK and LD isozymes were substantially less effective biomarkers and, in contrast to cTnT, were ineffective markers in the presence of moderate skeletal muscle injury, with resulting serum CK activity > 5,000 U/L. Using these animal models, and mouse and ferret models, we also showed cTnT to be an effective biomarker in doxorubicin cardiotoxicosis, traumatic injury, ischemia, and cardiac puncture. Reference range serum concentrations for all species were at the detection limit of the assay, except those for mice, in which they were slightly increased, possibly because mice were used to generate assay monoclonal antibodies. We conclude that cTnT is a powerful biomarker in laboratory animals for the sensitive and specific detection of cardiac injury arising from various causes.

The presence of estrogen receptor protein and estrogen receptor messenger RNA was revealed in peripheral ganglionic neurons of the rat. The pelvic parasympathetic autonomic ganglion and lumbosacral dorsal root sensory ganglia were examined for estrogen receptor-containing neurons because they have known projections to the uterus and uterine cervix. The vagal nodose ganglia were studied for estrogen receptor-containing neurons because they are suspected sources of influence on the uterus. Immunohistochemistry. in situ hybridization histochemistry and retrograde tracing were utilized. Immunoreactivity for estrogen receptors was evident in the nuclei of a subpopulation of neurons in the pelvic ganglia, sixth lumbar and first sacral dorsal root ganglia and nodose ganglia. Some estrogen receptor-positive neurons also contained the retrograde tracer FluoroGold that previously had been injected into the uterus and uterine cervix. Estrogen receptor messenger RNA was also evident in a subpopulation of ganglionic neurons. These data suggest that a certain population of neurons in autonomic and sensory ganglia are capable of synthesizing estrogen receptors and these receptors can serve as binding sites for estrogen. Thus, certain aspects of the structure, function and neurochemistry of some autonomic and sensory neurons may be influenced by the sex steroid estrogen.