Cascading effects of composts and cover crops on soil chemistry, bacterial communities and the survival of foodborne pathogens.

AIMS: Recent foodborne disease outbreaks have caused farmers to re-evaluate their practices. In particular, concern that soil amendments could introduce foodborne pathogens onto farms and promote their survival in soils has led farmers to reduce or eliminate the application of animal-based composts. However, organic amendments (such as composts and cover crops) could bolster food safety by increasing soil microbial diversity and activity, which can act as competitors or antagonists and reduce pathogen survival. METHODS AND RESULTS: Leveraging a study of a 27-year experiment comparing organic and conventional soil management, we evaluate the impacts of composted poultry litter and cover crops on soil chemistry, bacterial communities and survival of Salmonella enterica and Listeria monocytogenes. We found that bacterial community composition strongly affected pathogen survival in soils. Specifically, organic soils managed with cover crops and composts hosted more macronutrients and bacterial communities that were better able to suppress Salmonella and Listeria. For example, after incubating soils for 10 days at 20°C, soils without composts retained fourfold to fivefold more Salmonella compared to compost-amended soils. However, treatment effects dissipated as bacterial communities converged over the growing season. CONCLUSIONS: Our results suggest that composts and cover crops may be used to build healthy soils without increasing foodborne pathogen survival. SIGNIFICANCE AND IMPACT OF THE STUDY: Our work suggests that animal-based composts do not promote pathogen survival and may even promote bacterial communities that suppress pathogens. Critically, proper composting techniques are known to reduce pathogen populations in biological soil amendments of animal origin, which can reduce the risks of introducing pathogens to farm fields in soil amendments. Thus, animal-based composts and cover crops may be a safe alternative to conventional fertilizers, both because of the known benefits of composts for soil health and because it may be possible to apply amendments in such a way that food-safety risks are mitigated rather than exacerbated.

The reaction of O+(4S) ions with H2, HD, and D2 at low temperatures: Experimental study of the isotope effect.

The reactions of the O+ ions in the 4S electronic ground state with D2 and HD were studied in a cryogenic 22-pole radio-frequency ion trap in the temperature range of 15 K-300 K. The obtained reaction rate coefficients for both reactions are, considering the experimental errors, nearly independent of temperature and close to the values of the corresponding Langevin collisional reaction rate coefficients. The obtained branching ratios for the production of OH+ and OD+ in the reaction of O+(4S) with HD do not change significantly with temperature and are consistent with the results obtained at higher collisional energies by other groups. Particular attention was given to ensure that the O+ ions in the trap are in the ground electronic state.

Patterns of emergency ambulance use, 2009-13: a comparison of older people living in Residential Aged Care Facilities and the Community.

OBJECTIVE: to examine demand for emergency ambulances by older people. DESIGN: retrospective cohort study using secondary analysis of routinely collected clinical and administrative data from Ambulance Victoria, and population data from the Australian Bureau of Statistics and the Australian Institute of Health and Welfare. SETTING: Victoria, Australia. PARTICIPANTS: people aged 65 years and over, living in Residential Aged Care Facilities (RACF) and the community, attended by emergency ambulance paramedics, 2009-13. MAIN OUTCOME MEASURES: rates of emergency ambulance attendance. RESULTS: older people living in RACF experienced high rates of emergency ambulance attendance, up to four times those for age- and sex-matched people living in the community. Rates remained constant during the study period equating to a consistent, 1.45% average annual increase in absolute demand. Rates peak among the 80-84-year group where the number of attendances equates to greater than one for every RACF-dwelling person each year. Increased demand was associated with winter months, increasing age and being male. CONCLUSION: these data provide strong evidence of high rates of emergency ambulance use by people aged 65 years and over living in RACF. These results demonstrate a clear relationship between increased rate of ambulance use among this vulnerable group of older Australians and residence, sex, age and season. Overall, absolute demand continues to increase each year adding to strain on health resources. Additional research is needed to elucidate individual characteristics, illness and health system contributors to ambulance use to inform strategies to appropriately reduce demand.

Early childhood development: impact of national human development, family poverty, parenting practices and access to early childhood education.

BACKGROUND: This study was to describe and quantify the relationships among family poverty, parents' caregiving practices, access to education and the development of children living in low- and middle-income countries (LAMIC). METHODS: We conducted a secondary analysis of data collected in UNICEF's Multiple Indicator Cluster Surveys (MICS). Early childhood development was assessed in four domains: language-cognitive, physical, socio-emotional and approaches to learning. Countries were classified into three groups on the basis of the Human Development Index (HDI). RESULTS: Overall, data from 97 731 children aged 36 to 59 months from 35 LAMIC were included in the after analyses. The mean child development scale score was 4.93 out of a maximum score of 10 (95%CI 4.90 to 4.97) in low-HDI countries and 7.08 (95%CI 7.05 to 7.12) in high-HDI countries. Family poverty was associated with lower child development scores in all countries. The total indirect effect of family poverty on child development score via attending early childhood education, care for the child at home and use of harsh punishments at home was -0.13 SD (77.8% of the total effect) in low-HDI countries, -0.09 SD (23.8% of the total effect) in medium-HDI countries and -0.02 SD (6.9% of the total effect) in high-HDI countries. CONCLUSIONS: Children in the most disadvantaged position in their societies and children living in low-HDI countries are at the greatest risk of failing to reach their developmental potential. Optimizing care for child development at home is essential to reduce the adverse effects of poverty on children's early development and subsequent life.

Common mental disorders among women, social circumstances and toddler growth in rural Vietnam: a population-based prospective study.

BACKGROUND: Common mental disorders (CMD) and adverse social circumstances are widespread among mothers of infants and toddlers in resource-constrained settings. These can undermine early childhood development through compromised caregiving and insufficient access to essential resources. The aim was to examine the effect of maternal CMD and social adversity in the post-partum year on toddler's length-for-age index in a rural low-income setting. METHODS: A population-based prospective cohort study of women in Ha Nam province, Vietnam who completed baseline assessments in either late pregnancy or 4-6 weeks post partum and were followed up, with their toddlers, 15 months later. CMD were assessed at both points by psychiatrist-administered Structured Clinical Interviews for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Diagnoses. Anthropometric indices were calculated from toddler's age, sex, weight and length using World Health Organization Child Growth Standards. Social adversities were assessed by study-specific questions and locally validated psychometric instruments. The hypothesized model of factors governing toddler's length-for-age Z score (LAZ) was tested using path analysis. RESULTS: In total, 211/234 (90.1%) mother-toddler pairs provided complete data. Baseline prevalence of CMD among women was 33.6% and follow-up was 18.5%. The mean LAZ among toddlers was -1.03 and stunting prevalence (LAZ < -2) was 15.6%. Maternal CMD at baseline were indirectly related to toddler LAZ via maternal CMD at follow-up (regression coefficient = -0.05, 95% CI -0.11 to -0.01). Maternal CMD at follow-up was associated significantly with toddler LAZ (regression coefficient = -0.15, 95% CI -0.28 to -0.05). Poorer quality of marital relationship, mothers' experiences of childhood abuse and <30 days dedicated post-partum care were associated indirectly with lower toddler LAZ via maternal CMD. CONCLUSIONS: Maternal post-natal CMD are associated with child growth measured by LAZ in this resource-constrained setting. Social adversities affect child growth indirectly through increasing the risk of maternal CMD. Interventions to reduce stunting in low-income settings may need to address maternal CMD and social adversities in order to improve impact.

A Cadaveric Study of the Carpal Tunnel and Anatomical Variations of the Median Nerve in Vietnamese Adults: Implications for Single Portal Endoscopic Carpal Tunnel Release.

Introduction: Single-portal endoscopic carpal tunnel release using modified Agee technique is widely used in Vietnam. Yet information on the anatomy of the target space of Vietnamese people regarding this technique is scarce. We aimed to characterise the anatomical landmarks and variations of the carpal tunnel to propose a safer surgery. Materials and methods: All twenty hands of ten fresh frozen, unembalmed cadavers of Vietnamese adults were included. Dissection was performed after the vertical line, Kaplan's cardinal line and the distal wrist crease were drawn. The transverse carpal ligament (TCL), ulnar neurovascular bundle and superficial palmar arch were exposed. Measurements were made using Mitutoyo calliper. The variants of the median nerve and in the course of the thenar motor branch were recorded. Results: The median distances from the TCL distal margin to the distal wrist crease and superficial palmar arch were 31.2mm and 12.7mm, respectively. The ulnar neurovascular bundle was located 5.7mm and 4.4mm ulnar to the vertical line at the level of the TCL proximal margin and at the level of the TCL distal margin, respectively. The thenar motor branch of the median nerve was extra-ligamentous in 19 hands and preligamentous in 1 hand. Conclusion: If endoscopic portal is made along the distal wrist crease, blade assembly should not be inserted beyond the 35mm mark on its scale. Instruments should be aimed toward the radial border of the patient's ring finger. Surgeons should be aware of the preligamentous course of the thenar motor branch although this variant type is rare.

Structure-based discovery of interleukin-33 inhibitors: a pharmacophore modelling, molecular docking, and molecular dynamics simulation approach.

Interleukin (IL)-33 is a new cytokine of the IL-1 family that is related to several inflammatory and autoimmune diseases. IL-33 binds to its ST2 receptor and leads to biological responses thereof. Currently, no drugs have been approved for the treatment of IL-33 related diseases. The aim of this study was to search for small molecules that inhibit the protein-protein interaction between IL-33 and ST2. A virtual screening was first performed to identify potential molecules that can bind IL-33. By analysing the interactions between key residues in the complex of IL-33/ST2, two pharmacophore hypotheses were then generated based on the 'mimicry' and 'pair-rule' principles. From a database of 62,074 compounds, 60 molecules satisfying the pharmacophore models were identified and docked to IL-33. Among 35 compounds successfully docked into the protein, 9 potential ligands in complex with IL-33 were selected for further analysis by molecular dynamics simulations. Based on the stability of the complexes and the interactions of each ligand with the key residues of IL-33, two compounds DB00158 and DB00642 were identified as the most potential inhibitors that can be further investigated as promising novel IL-33 inhibitory drugs.

Inheritance of proliferative breast disease in breast cancer kindreds.

Previous studies have emphasized that genetic susceptibility to breast cancer is rare and is expressed primarily as premenopausal breast cancer, bilateral breast cancer, or both. Proliferative breast disease (PBD) is a significant risk factor for the development of breast cancer and appears to be a precursor lesion. PBD and breast cancer were studied in 103 women from 20 kindreds that were selected for the presence of two first degree relatives with breast cancer and in 31 control women. Physical examination, screening mammography, and four-quadrant fine-needle breast aspirates were performed. Cytologic analysis of breast aspirates revealed PBD in 35% of clinically normal female first degree relatives of breast cancer cases and in 13% of controls. Genetic analysis suggests that genetic susceptibility causes both PBD and breast cancer in these kindreds. This study supports the hypothesis that this susceptibility is responsible for a considerable portion of breast cancer, including unilateral and postmenopausal breast cancer.

Peramivir binding affinity with influenza A neuraminidase and research on its mutations using an induced-fit docking approach.

Influenza A virus (IAV) has caused epidemic infections worldwide, with many strains resistant to inhibitors of a surface protein, neuraminidase (NA), due to point mutations on its structure. A novel NA inhibitor named peramivir was recently approved, but no exhaustive computational research regarding its binding affinity with wild-type and mutant NA has been conducted. In this study, a thorough investigation of IAV-NA PDB entries of 9 subtypes is described, providing a list of residues constituting the protein-ligand binding sites. The results of induced-fit docking approach point out key residues of wild-type NA participating in hydrogen bonds and/or ionic interactions with peramivir, among which Arg 368 is responsible for a peramivir-NA ionic interaction. Mutations on this residue greatly reduced the binding affinity of peramivir with NA, with 3 mutations R378Q, R378K and R378L (NA6) capable of deteriorating the docking performance of peramivir by over 50%. 200 compounds from 6-scaffolds were docked into these 3 mutant versions, revealing 18 compounds giving the most promising results. Among them, CMC-2012-7-1527-56 (benzoic acid scaffold, IC50 = 32 nM in inhibitory assays with IAV) is deemed the most potential inhibitor of mutant NA resisting both peramivir and zanamivir, and should be further investigated.

An inhibitory interaction of human cortical responses to stimuli preferentially exciting Adelta or C fibers.

Finely myelinated (type Adelta) and unmyelinated (type C) fibers are the major afferent inputs to spinothalamic tract neurons mediating sensory and reflex responses to noxious and thermal stimuli. These two fiber types differ in their sensory and biophysical properties, raising questions about the interaction of their supraspinal responses. Therefore, we investigated the interaction of cortical responses to stimuli that preferentially excite these fibers in human subjects using evoked potential recordings in a paired conditioning stimulation (CS) and test stimulation (TS) paradigm. There were two experiments, one with Adelta as CS and C as TS (Adelta-C) and another with these stimuli reversed (C-Adelta). We used intra-epidermal electrical pulses applied to the dorsal left hand at 2x and 1x pinprick threshold (pp) for the preferential stimulation of Adelta fibers and 37-50 degrees C contact heat pulses applied to the left or right thenar and left hypothenar eminences for the preferential stimulation of C fibers. We found that the cortical response to preferential Adelta or C fiber stimulation was attenuated whenever either cortical response preceded the other. Standardized values of peak and integrated amplitudes were <1 in all pairing conditions and in all subjects in both experiments. The suppressive effect varied in magnitude with the intensity of the conditioning stimulus in both Adelta-C and C-Adelta experiments. Furthermore, intra-segmental interaction was differentially effective for Adelta conditioning (peak amplitude, P<0.008; analysis of variance). Our experiments provide the first neurophysiological evidence for a somatotopically distributed, mutually suppressive interaction between cortical responses to preferentially activated Adelta and C afferents in humans. This suppressive interaction of cortical responses suggests contrasting and possibly mutually exclusive sensorimotor functions mediated through the Adelta and C fiber afferent channels.

Transient receptor potential melastatin 4 channel is required for rat dental pulp stem cell proliferation and survival.

OBJECTIVES: Investigate the role of the transient receptor potential melastatin 4 (TRPM4) channel in rat dental pulp stem cell (DPSC) proliferation and survival. MATERIALS AND METHODS: Immunofluorescence and FACS analysis were used to detect the stem cell marker CD90. Alizarin Red S and Oil Red O staining were used to identify osteoblast and adipocyte differentiation, respectively. To characterize TRPM4, patch-clamp recordings were obtained from single cells in the whole-cell configuration mode. The significance of TRPM4 for proliferation and survival was examined with 9-phenanthrol, a TRPM4 inhibitor during a 96-hour period of culture. Real-time Ca2+ imaging analysis with Fura-2AM was used to investigate the impact of TRPM4 on intracellular Ca2+ signals. RESULTS: DPSCs were CD90-positive and differentiated into osteoblasts. Patch-clamp recordings revealed currents typical of TRPM4 that were Ca2+ -activated, voltage-dependent and Na+ -conducting. Inhibition of TRPM4 resulted in a significant reduction in the cell population after a 96-hr period of culture and transformed the biphasic pattern of intracellular Ca2+ signalling into sustained oscillations. CONCLUSIONS: Rat DPSCs have stem cell characteristics and functional TRPM4 channels that are required for proliferation and survival. These data suggest that the shape and frequency of intracellular Ca2+ signals may mediate stem cell proliferation and survival.

A large kindred with 17q-linked breast and ovarian cancer: genetic, phenotypic, and genealogical analysis.

BACKGROUND: Mutation of a specific, but as yet unidentified, gene BRCA1 on chromosome 17q results in increased susceptibility to breast and ovarian cancer. It is important to know the effects of this gene in terms of the age-specific risks of these cancers and the potential interaction of this gene with other known risk factors. PURPOSE: We performed detailed studies on a large multigenerational family, in which there is known 17q-linked breast and ovarian cancer, in order to characterize the effects of the BRCA1 mutation on development of breast and ovarian cancer. METHODS: Data from the Utah Population Database were used to identify a family (identified as K2082) with a cluster of premenopausal breast cancer and ovarian cancer at any age. Blood samples from 195 members of the family were obtained and these individuals were genotyped for a series of four chromosome 17q polymorphic markers. Information on reproductive history, cancer incidence and treatment, and lifestyle factors was collected on 72 women in the family by questionnaire or through contact with living relatives. RESULTS: Odds in favor of linkage of breast and ovarian cancer in this family to the BRCA1 region of chromosome 17q are greater than 10(8) to 1. The estimated risks for breast or ovarian cancer because of the BRCA1 mutation in this family are 40% by age 50 years and 90% by age 70. No differences between affected and unaffected older BRCA1 gene carriers were observed for a number of known epidemiologic risk factors for these cancers. The gender of the parent from whom the mutant BRCA1 allele was inherited was significantly associated with phenotypic expression (P = .04). A recombinant which places BRCA1 distal to the marker Mfd191 was observed. CONCLUSIONS: Women with the BRCA1 mutation are at increased risk of developing breast and ovarian cancer. In our study population, the mutation appears to confer a lower risk of cancer at younger ages than found in previous studies. Continued interaction with family K2082 will be useful in longitudinal follow-up studies and in studies of the psychosocial implications of providing DNA diagnosis of BRCA1.

Machine learning-, rule- and pharmacophore-based classification on the inhibition of P-glycoprotein and NorA.

The efflux pumps P-glycoprotein (P-gp) in humans and NorA in Staphylococcus aureus are of great interest for medicinal chemists because of their important roles in multidrug resistance (MDR). The high polyspecificity as well as the unavailability of high-resolution X-ray crystal structures of these transmembrane proteins lead us to combining ligand-based approaches, which in the case of this study were machine learning, perceptual mapping and pharmacophore modelling. For P-gp inhibitory activity, individual models were developed using different machine learning algorithms and subsequently combined into an ensemble model which showed a good discrimination between inhibitors and noninhibitors (acctrain-diverse = 84%; accinternal-test = 92% and accexternal-test = 100%). For ligand promiscuity between P-gp and NorA, perceptual maps and pharmacophore models were generated for the detection of rules and features. Based on these in silico tools, hit compounds for reversing MDR were discovered from the in-house and DrugBank databases through virtual screening in an attempt to restore drug sensitivity in cancer cells and bacteria.

Investigation of Fucoidan-Oleic Acid Conjugate for Delivery of Curcumin and Paclitaxel.

Nanoparticles for a specific delivery are likely to be designed for cancer therapeutic effectiveness and improvement. In this study, a fucoidan-oleic acid conjugate was prepared and investigated in terms of loading capacity for poorly water-soluble anti-cancer drugs to maximize effectiveness of the treatment. Fucoidan was used as a hydrophilic portion of an amphiphilic structure for improving cancer therapeutic effects. Paclitaxel and curcumin were chosen as other model drugs loaded in the conjugates. The results showed that self-assembled nanoparticles with different sizes and morphologies could be prepared with two different concentrations of oleic acid as hydrophobic portion. Moreover, loading efficiency and release patterns of these drugs were mainly dependent on the hydrophobic interaction between drugs and oleic acid. It was also revealed that fucoidan and curcumin were released higher at pH 4.5 than at the physiological condition (pH 7.4), thus, facilitating the delivery and maximizing effects of the anticancer agents on cancer cells. On the contrary, paclitaxel from fucoidan nanoparticles was released faster at pH 7.4. The exploration of fucoidan-oleic acid conjugate could be considered as promising nanomedicines for cancer therapeutics.

Three- and four-class classification models for P-glycoprotein inhibitors using counter-propagation neural networks.

P-glycoprotein (P-gp) is an ATP binding cassette (ABC) transporter that helps to protect several certain human organs from xenobiotic exposure. This efflux pump is also responsible for multi-drug resistance (MDR), an issue of the chemotherapy approach in the fight against cancer. Therefore, the discovery of P-gp inhibitors is considered one of the most popular strategies to reverse MDR in tumour cells and to improve therapeutic efficacy of commonly used cytotoxic drugs. Until now, several generations of P-gp inhibitors have been developed but they have largely failed in preclinical and clinical studies due to lack of selectivity, poor solubility and severe pharmacokinetic interactions. In this study, three models (SION, SIO, SIN) to classify specific 'true' P-gp inhibitors as well as three other models (CPBN, CPB1, CPN) to distinguish between P-gp inhibitors, CYP 3A inhibitors and co-inhibitors of these proteins with rather high accuracy values for the test set and the external set were generated based on counter-propagation neural networks (CPG-NN). Such three and four-class classification models helped provide more information about the bioactivities of compounds not only on one target (P-gp), but also on a combination of multiple targets (P-gp, CYP 3A).

A comparative magnetoencephalographic study of cortical activations evoked by noxious and innocuous somatosensory stimulations.

We recorded somatosensory-evoked magnetic fields and potentials produced by painful intra-epidermal stimulation (ES) and non-painful transcutaneous electrical stimulation (TS) applied to the left hand in 12 healthy volunteers to compare cortical responses to noxious and innocuous somatosensory stimulations. Our results revealed that cortical processing following noxious and innocuous stimulations was strikingly similar except that the former was delayed approximately 60 ms relative to the latter, which was well explained by a difference in peripheral conduction velocity mediating noxious (Adelta fiber) and innocuous (Abeta fiber) inputs. The first cortical activity evoked by both ES and TS was in the primary somatosensory cortex (SI) in the hemisphere contralateral to the stimulated side. The following activities were in the bilateral secondary somatosensory cortex (SII), insular cortex, cingulate cortex, anterior medial temporal area and ipsilateral SI. The source locations did not differ between the two stimulus modalities except that the dipole for insular activity following ES was located more anterior to that following TS. Both ES and TS evoked vertex potentials consisting of a negativity followed by a positivity at a latency of 202 and 304 ms, and 134 and 243 ms, respectively. The time course of the vertex potential corresponded to that of the activity of the medial temporal area. Our results suggested that cortical processing was similar between noxious and innocuous stimulation in SI and SII, but different in insular cortex. Our data also implied that activities in the amygdala/hippocampal formation represented common effects of noxious and tactile stimulations.

Cerebral activation by the signals ascending through unmyelinated C-fibers in humans: a magnetoencephalographic study.

Cerebral processing of first pain, associated with A delta-fibers, has been studied intensively, but the cerebral processing associated with unmyelinated C-fibers, relating to second pain, remains to be investigated. This is the first study to clarify the primary cortical processing of second pain by magnetoencephalography, through the selective activation of C-fibers, by the stimulation of a tiny area of skin with a CO2 laser. In the hemisphere contralateral to the side stimulated, a one-source generator in the upper bank of the Sylvian fissure (secondary somatosensory cortex, SII) or two-source generators in SII and the hand area of the primary somatosensory cortex (SI) were the optimal configurations for the first component 1M. The onset and peak latency of the two sources in SI and SII were not significantly different. In the hemisphere ipsilateral to the stimulation, only one source was estimated in SII, and its peak latency was significantly (approximately 18 ms on average) longer than that of the SII source in the contralateral hemisphere. From our findings we suggest that parallel activation of SI and SII contralateral to the stimulation represents the first step in the cortical processing of C-fiber-related activities, probably related to second pain.

Critical periods for the effects of alcohol exposure on learning in rats.

Critical periods for alcohol-induced deficits in spatial navigation and passive avoidance learning were investigated with a rat model of fetal alcohol syndrome. Rats were exposed to alcohol prenatally (Gestational Days 1-10 or 11-22) or postnatally (Postnatal Days 2-10) or throughout all 3 periods. Offspring were tested in either a spatial navigation or an avoidance task as juveniles or adults. As juveniles, the combined exposure group took longer to learn the spatial navigation task compared with all other groups. This effect was not seen in adults. Passive avoidance performance was not affected. These results suggest that long-term exposure to alcohol during development has adverse effects on spatial learning. The lack of differences in the short-term exposure groups implies that there may not be 1 critical period of alcohol exposure, but that the adverse effects of alcohol during development may be cumulative on some behaviors.

Plasticity of postganglionic sympathetic neurons in the rat superior cervical ganglion after axotomy.

The neuropeptides galanin (GAL) and vasoactive intestinal polypeptide (VIP) are upregulated in spinal and vagal sensory as well as in cranial motor neurons after axonal transection. In this study an increase of both peptides is demonstrated in axotomized principal ganglionic neurons (PGN) of the rat sympathetic superior cervical ganglion by use of double-labeling immunofluorescence. Compared to control ganglia that do not contain more than 1% GAL- or VIP-positive cells, about 26% of all PGN exhibit GAL immunoreactivity by day 1 after transection of the major postganglionic branches. The proportion of immunoreactive neurons reaches its maximum after 30 days (40%) and decreases to about 27% within the second month after axotomy. The percentage of VIP-positive neurons is much lower than for GAL: 2% of the PGN exhibit VIP immunoreactivity at day 1 and about 7% are observed 30 and 60 days after axotomy. In order to further characterize newly GAL- and VIP-positive PGN, their cell diameters were determined 12 days after axotomy. Compared to the mean overall neuron diameter of 24.8 microns, GAL-immunoreactive neurons are predominantly of small and intermediate size (22.2 microns), whereas VIP occurs mainly in larger neurons (26.1 microns). Besides cell bodies, many intraganglionic nerve fibers stain positive for GAL or VIP, particularly at day 6. Most likely, these fibers represent axons, as indicated by the absence of MAP2, a cytoskeletal protein found in neuronal somata and dendrites. They establish direct membrane contacts with postganglionic perikarya, as revealed by pre-embedding immuno-electron microscopy. Some cell bodies and fibers contain both peptides. Colocalization of GAL or VIP with tyrosine hydroxylase (TH), the rate-limiting enzyme of catecholamine synthesis, reveals a reduced immunoreactivity for TH in intensely GAL- or VIP-positive cells, and vice versa at day 6. However, no difference in staining intensity for VIP or GAL, and TH, is observed after 30 and 60 days. Possible implications of GAL and VIP for peripheral nerve regeneration and their regulation by target-derived factors are discussed.

Comparison of compound and cross-modal training on postoperative visual relearning of visual decorticate rats.

The effects of postoperative bimodal compound conditioning and cross-modal transfer of learning on behavior were compared by training rats prior to visual decortication to avoid shock with visual intensity cues. On Postop Day 6, rats were given avoidance training in one of three cue conditions: auditory intensity cues (cross-modal), paired auditory and visual cues (compound conditioning), or no cues (no-training control). On Postop Day 7 rats in the no-training control and the cross-modal transfer conditions were retrained with the visual discrimination while rats in the compound conditioning group were either retrained with the visual intensity cue or trained with the auditory intensity cue. Postoperative cross-modal transfer training enhanced visual relearning whereas bimodal compound conditioning interfered with relearning. However, compound conditioning facilitated subsequent auditory discrimination learning. These results support the notion of an injury-induced neurological bias that is increased after bimodal compound conditioning and reduced after cross-modal training. Potential implications for neurological rehabilitation are also discussed.