Neonatal hemophagocytic lymphohistiocytosis: A meta-analysis of 205 cases.

BACKGROUND: Neonatal hemophagocytic lymphohistiocytosis (nHLH), defined as HLH that presents in the first month of life, is clinically devastating. There have been few large descriptive studies of nHLH. OBJECTIVES: The objective of this study was to perform a meta-analysis of published cases of nHLH. METHODS: A comprehensive literature database search was performed. Cases of HLH were eligible for inclusion if clinical analysis was performed at age ≤30 days. Up to 70 variables were extracted from each case. RESULTS: A total of 544 studies were assessed for eligibility, and 205 cases of nHLH from 142 articles were included. The median age of symptom onset was day of life 3 (interquartile range [IQR]: 0-11, n = 141). Median age at diagnosis was day of life 15 (IQR: 6-27, n = 87). Causes of HLH included familial HLH (48%, n = 99/205), infection (26%, n = 53/205), unknown (17%, n = 35/205), macrophage activation syndrome/rheumatologic (2.9%, n = 4/205), primary immune deficiency (2.0%, n = 5/205), inborn errors of metabolism (2.4%, n = 5/205), and malignancy (2.0%, n = 4/205). Fever was absent in 19% (n = 28/147) of all neonates and 39% (n = 15/38) of preterm neonates. Bicytopenia was absent in 26% (n = 47/183) of patients. Central nervous system (CNS) manifestations were reported in 63% of cases (n = 64/102). Liver injury (68%, n = 91/134) and/or liver failure (24%, n = 32/134) were common. Flow cytometry was performed in 22% (n = 45/205) of cases. Many patients (63%, n = 121/193) died within the period of reporting. Discernable values for HLH diagnostic criteria were reported between 30% and 83% of the time. CONCLUSIONS: Evaluation of nHLH requires rapid testing for a wide range of differential diagnoses. HLH diagnostic criteria such as fever and bicytopenia may not occur as frequently in the neonatal population as in older pediatric populations. Neurologic and hepatic manifestations frequently occur in the neonatal population. Current reports of nHLH suggest a high mortality rate. Future publications containing data on nHLH should improve reporting quality by reporting all clinically relevant data.

Camera-Robot Calibration for the da Vinci® Robotic Surgery System.

The development of autonomous or semi-autonomous surgical robots stands to improve the performance of existing teleoperated equipment, but requires fine hand-eye calibration between the free-moving endoscopic camera and patient-side manipulator arms (PSMs). A novel method of solving this problem for the da Vinci® robotic surgical system and kinematically similar systems is presented. First, a series of image-processing and optical-tracking operations are performed to compute the coordinate transformation between the endoscopic camera view frame and an optical-tracking marker permanently affixed to the camera body. Then, the kinematic properties of the PSM are exploited to compute the coordinate transformation between the kinematic base frame of the PSM and an optical marker permanently affixed thereto. Using these transformations, it is then possible to compute the spatial relationship between the PSM and the endoscopic camera using only one tracker snapshot of the two markers. The effectiveness of this calibration is demonstrated by successfully guiding the PSM end effector to points of interest identified through the camera. Additional tests on a surgical task, namely grasping a surgical needle, are also performed to validate the proposed method. The resulting visually-guided robot positioning accuracy is better than the earlier hand-eye calibration results reported in the literature for the da Vinci® system, while supporting intraoperative update of the calibration and requiring only devices that are already commonly used in the surgical environment.

Fully-automated, high-throughput micro-computed tomography analysis of body composition enables therapeutic efficacy monitoring in preclinical models.

BACKGROUND: The ability to non-invasively measure body composition in mouse models of obesity and obesity-related disorders is essential for elucidating mechanisms of metabolic regulation and monitoring the effects of novel treatments. These studies aimed to develop a fully automated, high-throughput micro-computed tomography (micro-CT)-based image analysis technique for longitudinal quantitation of adipose, non-adipose and lean tissue as well as bone and demonstrate utility for assessing the effects of two distinct treatments. METHODS: An initial validation study was performed in diet-induced obesity (DIO) and control mice on a vivaCT 75 micro-CT system. Subsequently, four groups of DIO mice were imaged pre- and post-treatment with an experimental agonistic antibody specific for anti-fibroblast growth factor receptor 1 (anti-FGFR1, R1MAb1), control immunoglobulin G antibody, a known anorectic antiobesity drug (rimonabant, SR141716), or solvent control. The body composition analysis technique was then ported to a faster micro-CT system (CT120) to markedly increase throughput as well as to evaluate the use of micro-CT image intensity for hepatic lipid content in DIO and control mice. Ex vivo chemical analysis and colorimetric analysis of the liver triglycerides were performed as the standard metrics for correlation with body composition and hepatic lipid status, respectively. RESULTS: Micro-CT-based body composition measures correlate with ex vivo chemical analysis metrics and enable distinction between DIO and control mice. R1MAb1 and rimonabant have differing effects on body composition as assessed by micro-CT. High-throughput body composition imaging is possible using a modified CT120 system. Micro-CT also provides a non-invasive assessment of hepatic lipid content. CONCLUSIONS: This work describes, validates and demonstrates utility of a fully automated image analysis technique to quantify in vivo micro-CT-derived measures of adipose, non-adipose and lean tissue, as well as bone. These body composition metrics highly correlate with standard ex vivo chemical analysis and enable longitudinal evaluation of body composition and therapeutic efficacy monitoring.

Fitness valleys constrain HIV-1's adaptation to its secondary chemokine coreceptor.

Fitness valleys, in which mutations at different loci are singly deleterious but jointly beneficial, arise because of reciprocal sign epistasis. Recent theoretical work provides analytical approximations of times to cross fitness valleys via three mechanisms: sequential fixation, stochastic tunnelling and recombination. These times depend critically on the effective population size (N(e)). Human immunodeficiency virus type 1 (HIV-1) encounters fitness valleys in adapting to its secondary cell-surface chemokine coreceptor, CXCR4. Adaptation to CXCR4 tends to occur late in infection and only in about 50% of patients and is associated with disease progression. It has been hypothesized that the need to cross fitness valleys may explain the delayed and inconsistent adaptation to CXCR4. We have identified four fitness valleys from a previous study of fitness epistasis in adaptation to CXCR4 and use estimates of the within-patient variance N(e) for different patient treatment statuses and infection stages (conditions) to estimate times to cross the valleys. These valleys may be crossed predominantly by stochastic tunnelling, although mean crossing times are consistently longer than the durations of the conditions for which they are calculated. These results were confirmed with stochastic simulation. Simulations show that crossing times for a given condition are highly variable and that for each condition there is a low probability of crossing each valley. These findings support the hypothesis that fitness valleys constrain the adaptation of HIV-1 to CXCR4. This study provides the first detailed analysis of the evolutionary dynamics associated with empirical fitness valleys.

A study of a pre-operative intervention in patients with diabetes undergoing cardiac surgery.

BACKGROUND: Coronary heart disease is common in Type 2 diabetes and often requires cardiac surgery. However poorer outcomes have been reported including increased rates of post-operative infection and prolonged hospital stay. AIM: The aim of the study was to determine the feasibility and acceptability of a specialist consultation model (pre-operative medical and educational intervention) for type 2 diabetes in the cardiac surgery setting. METHODS: Twenty four patients were assigned usual care or to the intervention group. The intervention group were assessed by a diabetes clinical nurse consultant, dietitian, and endocrinologist during a pre-operative visit. Specific diabetes questionnaires were administered, education was delivered, and protocol-driven changes to the medical regimen were instituted. Length of stay, incidence of post-operative complications, and number of post-operative inpatient review endocrinology visits required were recorded. RESULTS: Twenty four patients with a pre-operative HbA(1c) greater than 6.5% (48 mmol/mol) were studied (17 males and 7 females). In the usual care group (n = 15), HbA(1c) pre-operatively was 7.2% (55.2 mmol/mol) compared to 10.1% (86.9 mmol/mol) in the intervention group (n = 9). Six weeks post-operatively HbA(1c) fell significantly in the intervention group by 1.9% (to 8.2% [66.1 mmol/mol]) compared to a reduction of 1.2% (to 7.0% [53 mmol/mol]) in the usual care group (p < 0.05). No significant differences were observed in length of stay in intensive care or in total hospital stay between the groups: length of ICU stay 54 h for intervention versus 47 h for usual care, total hospital stay (mean 8 days for both); or in rates of post-operative infection. Differences were seen between in the diabetes questionnaires: in the Problem Areas in Diabetes questionnaire and in the Diabetes Treatment Satisfaction Questionnaire (p = 0.048). CONCLUSION: This small pilot feasibility study suggests there is potential benefit in the acute optimisation of diabetes treatment before elective cardiac surgery.

The effects of a novel inhibitor of tumor necrosis factor (TNF) alpha on prepulse inhibition and microglial activation in two distinct rodent models of schizophrenia.

Increased neuroinflammation has been shown in individuals diagnosed with schizophrenia (SCHZ). This study evaluated a novel immune modulator (PD2024) that targets the pro-inflammatory cytokine tumor necrosis factor-alpha (TNFα) to alleviate sensorimotor gating deficits and microglial activation employing two different rodent models of SCHZ. In Experiment 1, rats were neonatally treated with saline or the dopamine D2-like agonist quinpirole (NQ; 1 mg/kg) from postnatal day (P) 1-21 which produces increases of dopamine D2 receptor sensitivity throughout the animal's lifetime. In Experiment 2, rats were neonatally treated with saline or the immune system stimulant polyinosinic:polycytidylic acid (Poly I:C) from P5-7. Neonatal Poly I:C treatment mimics immune system activation associated with SCHZ. In both experiments, rats were raised to P30 and administered a control diet or a novel TNFα inhibitor PD2024 (10 mg/kg) in the diet from P30 until P67. At P45-46 and from P60-67, animals were behaviorally tested on auditory sensorimotor gating as measured through prepulse inhibition (PPI). NQ or Poly I:C treatment resulted in PPI deficits, and PD2024 treatment alleviated PPI deficits in both models. Results also revealed that increased hippocampal and prefrontal cortex microglial activation produced by neonatal Poly I:C was significantly reduced to control levels by PD2024. In addition, a separate group of animals neonatally treated with saline or Poly I:C from P5-7 demonstrated increased TNFα protein levels in the hippocampus but not prefrontal cortex, verifying increased TNFα in the brain produced by Poly I:C. Results from this study suggests that that brain TNFα is a viable pharmacological target to treat the neuroinflammation known to be associated with SCHZ.

A randomised controlled trial of energetic activity for depression in young people (READY): a multi-site feasibility trial protocol.

BACKGROUND: Prevalence of depression is increasing in young people, and there is a need to develop and evaluate behavioural interventions which may provide benefits equal to or greater than talking therapies or pharmacological alternatives. Exercise could be beneficial for young people living with depression, but robust, large-scale trials of effectiveness and the impact of exercise intensity are lacking. This study aims to test whether a randomised controlled trial (RCT) of an intervention targeting young people living with depression is feasible by determining whether it is possible to recruit and retain young people, develop and deliver the intervention as planned, and evaluate training and delivery. METHODS: The design is a three-arm cluster randomised controlled feasibility trial with embedded process evaluation. Participants will be help-seeking young people, aged 13-17 years experiencing mild to moderate low mood or depression, referred from three counties in England. The intervention will be delivered by registered exercise professionals, supported by mental health support workers, twice a week for 12 weeks. The three arms will be high-intensity exercise, low-intensity exercise, and a social activity control. All arms will receive a 'healthy living' behaviour change session prior to each exercise session and the two exercise groups are energy matched. The outcomes are referral, recruitment, and retention rates; attendance at exercise sessions; adherence to and ability to reach intensity during exercise sessions; proportions of missing data; adverse events, all measured at baseline, 3, and 6 months; resource use; and reach and representativeness. DISCUSSION: UK National Health Service (NHS) policy is to provide young people with advice about using exercise to help depression but there is no evidence-based exercise intervention to either complement or as an alternative to medication or talking therapies. UK National Institute for Health and Care Excellence (NICE) guidelines suggest that exercise can be an effective treatment, but the evidence base is relatively weak. This feasibility trial will provide evidence about whether it is feasible to recruit and retain young people to a full RCT to assess the effectiveness and cost-effectiveness of an exercise intervention for depression. TRIAL REGISTRATION: ISRCTN, ISRCTN66452702 . Registered 9 April 2020.

The plant cytoskeleton-cell-wall continuum.

Two of the most challenging mysteries of morphogenesis are how cells receive positional information from neighbouring cells and how receipt of this information triggers events that initiate cell differentiation. The concept that the cytoskeleton and éxocellular matrix' (ECM) form an interactive scaffold for perception and transduction of positional information is relatively new. Research is beginning to indicate that a continuous cytoskeleton-ECM scaffold may be a feature of all eukaryotic cells and that many of the molecules participating in this structure may be shared by plants, fungi and animals.

Regulation of nerve growth factor receptor gene expression in sympathetic neurons during development.

We used quantitative reverse transcription (RT)/PCR to study the regulation of p75 mRNA and trkA mRNA expression in the developing sympathetic neurons of the mouse superior cervical sympathetic ganglion (SCG) in vivo and in vitro. At E13, the SCG contains proliferating cells that express many features of differentiated neurons. These immature neurons survived in culture without NGF, and NGF did not induce c-fos expression. Low levels of p75 and trkA mRNAs were expressed at this stage in vivo. There was no significant increase in the level of either trkA mRNA or p75 mRNA in E13 control cultures up to 72 h in vitro, and neither NGF nor depolarizing levels of K+ ions (40 mM KC1) affected the expression of trkA mRNA. In E14 cultures, NGF induced c-fos expression in 10-15% of the neurons and enhanced the survival of a similar percentage of neurons. The proportion of neurons responding to NGF increased with age, reaching 90% in E18 cultures. The in vivo level of trkA mRNA increased markedly from E14 onward, but in contrast to sensory neurons (in which p75 and trkA mRNA levels increase in parallel), the level of trkA mRNA initially increased far more rapidly than that of p75 mRNA. After E17, the level of p75 mRNA increased rapidly and approached that of trkA mRNA postnatally, but at no stage did this exceed the level of trkA mRNA. In E14 cultures, the level of trkA mRNA increased in the absence of neurotrophins or 40 mM KC1. The level of p75 mRNA in E14 cultures was enhanced by NGF but was unaffected by 40 mM KC1. Our findings show that NGF receptor expression during the earliest stages of sympathetic neuron development is not affected by depolarization but indicate that by an early developmental stage (between E13 and E14 in vivo), sympathetic neurons become specified to upregulate trkA mRNA in culture independently of added factors. In addition, our findings reveal several distinctive features of p75 mRNA and trkA mRNA expression in sympathetic neurons compared with sensory neurons and provide a plausible explanation for previously observed differences in the effects of a p75 null mutation on the response of sensory and sympathetic neurons during embryonic and postnatal development.

Ectopic trkA expression mediates a NGF survival response in NGF-independent sensory neurons but not in parasympathetic neurons.

We have investigated the role of trkA, the tyrosine kinase NGF receptor, in mediating the survival response of embryonic neurons to NGF. Embryonic trigeminal mesencephalic (TMN) neurons, which normally survive in the presence of brain-derived neurotrophic factor (BDNF) but not NGF, become NGF-responsive when microinjected with an expression vector containing trkA cDNA. In contrast, microinjection of ciliary neurotrophic factor (CNTF)-dependent embryonic ciliary neurons with the same construct does not result in the acquisition of NGF responsiveness by these neurons despite de novo expression of trkA mRNA and protein. The failure of trkA to result in an NGF-promoted survival response in ciliary neurons is not due to absence of the low-affinity NGF receptor, p75, in these neurons. Quantitative RT/PCR and immunocytochemistry showed that TMN and ciliary neurons both express p75 mRNA and protein. These findings not only provide the first direct experimental demonstration of trkA mediating a physiological response in an appropriate cell type, namely NGF-promoted survival of embryonic neurons, but indicate that not all neurons are able to respond to a trkA-mediated signal transduction event.

Cytokine-induced nuclear factor kappa B activation promotes the survival of developing neurons.

Ciliary neurotrophic factor (CNTF), leukemia inhibitory factor (LIF), cardiotrophin-1 (CT-1), and interleukin 6 (IL-6) comprise a group of structurally related cytokines that promote the survival of subsets of neurons in the developing peripheral nervous system, but the signaling pathways activated by these cytokines that prevent neuronal apoptosis are unclear. Here, we show that these cytokines activate NF-kappaB in cytokine-dependent developing sensory neurons. Preventing NF-kappaB activation with a super-repressor IkappaB-alpha protein markedly reduces the number of neurons that survive in the presence of cytokines, but has no effect on the survival response of the same neurons to brain-derived neurotrophic factors (BDNF), an unrelated neurotrophic factor that binds to a different class of receptors. Cytokine-dependent sensory neurons cultured from embryos that lack p65, a transcriptionally active subunit of NF-kappaB, have a markedly impaired ability to survive in response to cytokines, but respond normally to BDNF. There is increased apoptosis of cytokine- dependent neurons in p65(-/)- embryos in vivo, resulting in a reduction in the total number of these neurons compared with their numbers in wild-type embryos. These results demonstrate that NF-kappaB plays a key role in mediating the survival response of developing neurons to cytokines.

Complications following removal of oesophageal foreign bodies: a retrospective review of 349 cases.

AIM: To determine the incidence and types of complications associated with oesophageal foreign body (FB) removal in dogs, as well as to evaluate potential risk factors for the development of complications. METHODS: Clinical records were searched within Animal Emergency Service and Veterinary Specialist Services databases between July 2001 and March 2017. Data were collected regarding signalment, FB type, method of removal, medical management and complications. Follow-up records from the referring veterinarian were then obtained by either phone call or email. RESULTS: A total of 349 FB cases were reviewed. The majority of FBs were bones (77.4%), with Staffordshire Bull Terriers (12.3%) and West Highland White Terriers (9.8%) the most common breeds seen. Complications at the time of FB removal occurred in 20 cases (5.9%), with 14 cases of perforation. Persistent gastrointestinal signs were reported in 4.7% of cases within the initial 72-h period following FB removal and 11.9% cases outside this time period. Respiratory signs such as dyspnoea and coughing were also reported in 8 cases (2.3%), all of which occurred within 72 h after FB removal. Follow-up of at least 1 month was available in 151 cases. Delayed complications occurred in 11 cases (7.3%), with stricture occurring in 4 cases (2.6%); 16 animals were either euthanased (n = 14) or died (n = 2) post-FB removal, resulting in a case fatality rate of 4.6%. CONCLUSION: Use of antacid medications and FB type did not have a statistically significant relationship with complications following FB removal.

Gait analysis in French bulldogs with and without vertebral kyphosis.

The study objective was to compare temporal-spatial and kinetic gait variables in neurologically normal French bulldogs with and without vertebral kyphosis. French bulldogs presented to a dedicated brachycephalic clinic were prospectively enrolled. All dogs underwent general physical, orthopaedic, and neurological examination prior to study inclusion. The presence of vertebral kyphosis was evaluated by computed tomography and kyphosis was defined as a Cobb angle exceeding 10°. Gait variables were collected using a pressure-sensitive GAITRite walkway with GAITFour software and included measurement of total pressure index (TPI) defined as the sum of peak pressure values recorded from each activated sensor by a paw during mat contact. Fifteen French bulldogs with (n=8) and without kyphosis (n=7) were included. Cobb angle in kyphotic dogs ranged from 14.9° to 39.5°. Univariate analyses were initially performed to examine the association between kyphosis and 16 gait variables. When those variables found to be associated (P<0.2) were taken forward into multivariate generalised linear mixed models (accounting for dog, velocity and side), kyphosis had a significant effect upon TPI of the forelimbs and TPI symmetry ratio (P<0.05); however, the size of these effects was small. Although vertebral kyphosis is rarely associated with neurological deficits, it was associated with subtle alterations in kinetic gait variables (TPI forelimbs and TPI symmetry ratio). Further studies are needed to evaluate the clinical importance of altered gait variables in French bulldogs with kyphosis.

Expression of the NGF receptor gene in sensory neurons and their cutaneous targets prior to and during innervation.

We have studied the expression of NGF receptor (NGFR) mRNA in the mouse trigeminal system at closely staged intervals throughout development. The level of NGFR mRNA per neuron is at a constant low level before the earliest axons reach the target field and increases 5-fold to plateau shortly after the arrival of the last axons. NGFR mRNA expression in developing target skin is restricted to mesenchyme, precedes the arrival of the earliest axons, and increases throughout the phase of target field innervation. These findings suggest that NGFR expression on sensory neurons occurs at a low level prior to target field innervation and is up-regulated with this event, and they raise the possibility that NGFRs on mesenchymal cells restrict the distribution of NGF in the target field.

Multiple roles for hepatocyte growth factor in sympathetic neuron development.

We have studied the role of hepatocyte growth factor (HGF)/Met signaling in the development of sympathetic neuroblasts and neurons. Anti-HGF antibodies reduced the number of sympathetic neuroblasts that differentiated into neurons, but neither anti-HGF antibodies nor HGF affected neuroblast proliferation. Anti-HGF antibodies also reduced the survival of neuroblasts but not sympathetic neurons. HGF greatly enhanced the neurite outgrowth of NGF-dependent sympathetic neurons throughout development. These in vitro effects of anti-HGF antibodies and HGF were abolished by a disabling mutation of Met, the HGF receptor tyrosine kinase. The Met mutation also increased sympathetic neuroblast apoptosis in vivo. Because Met and HGF are expressed in sympathetic ganglia throughout development, it is possible that the multiple effects of HGF/Met signaling on sympathetic neuroblasts and neurons occur in part by an autocrine mechanism.

Cell-Wall Polysaccharides of Developing Flax Plants.

Flax (Linum usitatissimum L.) fibers originate from procambial cells of the protophloem and develop in cortical bundles that encircle the vascular cylinder. We determined the polysaccharide composition of the cell walls from various organs of the developing flax plant, from fiber-rich strips peeled from the stem, and from the xylem. Ammonium oxalate-soluble polysaccharides from all tissues contained 5-linked arabinans with low degrees of branching, rhamnogalacturonans, and polygalacturonic acid. The fiber-rich peels contained, in addition, substantial amounts of a buffer-soluble, 4-linked galactan branched at the 0-2 and 0-3 positions with nonreducing terminal-galactosyl units. The cross-linking glycans from all tissues were (fucogalacto)xyloglucan, typical of type-I cell walls, xylans containing (1->)-[beta]-D-xylosyl units branched exclusively at the xylosyl O-2 with t-(4-O-methyl)-glucosyluronic acid units, and (galacto)glucomannans. Tissues containing predominantly primary cell wall contained a larger proportion of xyloglucan. The xylem cells were composed of about 60% 4-xylans, 32% cellulose, and small amounts of pectin and the other cross-linking polysaccharides. The noncellulosic polysaccharides of flax exhibit an uncommonly low degree of branching compared to similar polysaccharides from other flowering plants. Although the relative abundance of the various noncellulosic polysaccharides varies widely among the different cell types, the linkage structure and degree of branching of several of the noncellulosic polysaccharides are invariant.

The correlation between sampling site and gene expression in the term human placenta.

Using oligonucleotide microarrays we recently identified a set of transcripts that were up-regulated in hypoxic human trophoblasts. To test the hypothesis that expression of hypoxia-related placental transcripts depends on sampling site we analyzed nine different sites from term human placentas (n=6), obtained after uncomplicated pregnancies. These sites spanned the placental center to the lateral border and the basal to the chorionic plate. Relative gene expression at each site, determined using quantitative PCR, was correlated with villous histology. The expression of vascular endothelial growth factor (VEGF) and connective tissue growth factor (CTGF), the cytoskeleton proteins lamininA3 and alpha-tubulin, and the signal transduction protein Rad was enhanced in the subchorionic lateral border compared to medial basal site (1.6-2.9 fold, p<0.05). In contrast, the expression of NDRG1, adipophilin and human placental lactogen was unchanged. Enhanced villous maturation, syncytial knots and fibrin deposits were more frequent in the subchorionic placental lateral border, and correlated with up-regulation of hypoxia-related transcripts (p<0.05). The association between sample site and expression level was not observed in placentas with marginal cord insertion. The expression of hypoxia-related genes in the term human placenta is dependent on sampling site within the placental disk, likely reflecting local differences in villous perfusion.

Reduced age-related plasticity of neurotrophin receptor expression in selected sympathetic neurons of the rat.

Selective vulnerability of particular groups of neurons is a characteristic of the aging nervous system. We have studied the role of neurotrophin (NT) signalling in this phenomenon using rat sympathetic (SCG) neurons projecting to cerebral blood vessels (CV) and iris which are, respectively, vulnerable to and protected from atrophic changes during old age. RT-PCR was used to examine NT expression in iris and CV in 3- and 24-month-old rats. NGF and NT3 expression in iris was substantially higher compared to CV; neither target showed any alterations with age. RT-PCR for the principal NT receptors, trkA and p75, in SCG showed increased message during early postnatal life. However, during mature adulthood and old age, trkA expression remained stable while p75 declined significantly over the same period. In situ hybridization was used to examine receptor expression in subpopulations of SCG neurons identified using retrograde tracing. Eighteen to 20 h following local treatment of iris and CV with NGF, NT3 or vehicle, expression of NT receptor protein and mRNA was higher in iris- compared with CV-projecting neurons from both young and old rats. NGF and NT3 treatment had no effect on NT receptor expression in CV-projecting neurons at either age. However, similar treatment up-regulated p75 and trkA expression in iris-projecting neurons from 3-month-old, but not 24-month-old, rats. We conclude that lifelong exposure to low levels of NTs combined with impaired plasticity of NT receptor expression are predictors of neuronal vulnerability to age-related atrophy.

Quantitative assessment of dietary adherence in patients with insulin-dependent diabetes mellitus.

Research on the education of diabetic patients in diet management suffers from lack of an adequate method for describing patients' dietary behavior. In this report, a method is proposed for the quantitative assessment of dietary adherence in patients with IDDM. The method relies on comparisons between individualized diet plans and actual consumption as reflected by 24-h diet recalls. Data are presented that suggest this method has reliability and validity. In a sample of 97 patients with IDDM, nearly two-thirds adhered to the number and timing of planned feedings, while only about 10% of patients adhered to planned exchanges, 90% of the time. The average patient added or deleted one exchange for every four exchanges in the diet plan.