Behavior-driven arc expression is reduced in all ventral hippocampal subfields compared to CA1, CA3, and dentate gyrus in rat dorsal hippocampus.

Anatomical connectivity and lesion studies reveal distinct functional heterogeneity along the dorsal-ventral axis of the hippocampus. The immediate early gene Arc is known to be involved in neural plasticity and memory and can be used as a marker for cell activity that occurs, for example, when hippocampal place cells fire. We report here, that Arc is expressed in a greater proportion of cells in dorsal CA1, CA3, and dentate gyrus (DG), following spatial behavioral experiences compared to ventral hippocampal subregions (dorsal CA1 = 33%; ventral CA1 = 13%; dorsal CA3 = 23%; ventral CA3 = 8%; and dorsal DG = 2.5%; ventral DG = 1.2%). The technique used here to obtain estimates of numbers of behavior-driven cells across the dorsal-ventral axis, however, corresponds quite well with samples from available single unit recording studies. Several explanations for the two- to-threefold reduction in spatial behavior-driven cell activity in the ventral hippocampus can be offered. These include anatomical connectivity differences, differential gain of the self-motion signals that appear to alter the scale of place fields and the proportion of active cells, and possibly variations in the neuronal responses to non-spatial information within the hippocampus along its dorso-ventral axis.

Nonuniform allocation of hippocampal neurons to place fields across all hippocampal subfields.

The mechanisms governing how the hippocampus selects neurons to exhibit place fields are not well understood. A default assumption in some previous studies was the uniform random draw with replacement (URDWR) model, which, theoretically, maximizes spatial "pattern separation", and predicts a Poisson distribution of the numbers of place fields expressed by a given cell per unit area. The actual distribution of mean firing rates exhibited by a population of hippocampal neurons, however, is approximately exponential or log-normal in a given environment and these rates are somewhat correlated across multiple places, at least under some conditions. The advantage of neural activity-dependent immediate-early gene (IEG) analysis, as a proxy for electrophysiological recording, is the ability to obtain much larger samples of cells, even those whose activity is so sparse that they are overlooked in recording studies. Thus, a more accurate representation of the activation statistics can potentially be achieved. Some previous IEG studies that examined behavior-driven IEG expression in CA1 appear to support URDWR. There was, however, in some of the same studies, an under-recruitment of dentate gyrus granule cells, indicating a highly skewed excitability distribution, which is inconsistent with URDWR. Although it was suggested that this skewness might be related to increased excitability of recently generated granule cells, we show here that CA1, CA3, and subiculum also exhibit cumulative under-recruitment of neurons. Thus, a highly skewed excitability distribution is a general principle common to all major hippocampal subfields. Finally, a more detailed analysis of the frequency distributions of IEG intranuclear transcription foci suggests that a large fraction of hippocampal neurons is virtually silent, even during sleep. Whether the skewing of the excitability distribution is cell-intrinsic or a network phenomenon, and the degree to which this excitability is fixed or possibly time-varying are open questions for future studies. © 2016 Wiley Periodicals, Inc.

A founder mutation p.H701P identified as a major cause of SPG7 in Norway.

BACKGROUND AND PURPOSE: SPG7 is one of the most common forms of autosomal recessive hereditary spastic paraplegia. The phenotype has been shown to be heterogeneous, varying from a complex spastic ataxia to pure spastic paraplegia or pure ataxia. The aim of this study was to clinically and genetically characterize patients with SPG7 in Norway. METHODS: Six Norwegian families with a clinical diagnosis of hereditary spastic paraplegia were diagnosed with SPG7 through Sanger sequencing and whole-exome sequencing. Haplotypes were established to identify a possible founder mutation. All patients were thoroughly examined and the clinical and molecular findings are described. RESULTS: The core phenotype was spastic paraparesis with ataxia, bladder disturbances and progressive external ophthalmoplegia. The variant p.H701P was identified in homozygous state in one family and in compound heterozygous state in three families. Haplotype analysis of seven surrounding single nucleotide polymorphisms supports that this variant resides on a founder haplotype. Four of the families were compound heterozygous for the previously well-described p.A510V variant. CONCLUSION: SPG7 is a common subgroup of hereditary spinocerebellar disorders in Norway. The broad phenotype in the Norwegian SPG7 population illustrates the challenges with the traditional dichotomous classification of hereditary spinocerebellar disorders into hereditary spastic paraplegia or hereditary ataxia. A Norwegian founder mutation p.H701P was identified in four out of six families, making it a major cause of SPG7 in Norway.

Two cases of acute severe flaccid myelitis associated with enterovirus D68 infection in children, Norway, autumn 2014.

Enterovirus D68 (EV-D68), phylogenetic clade B was identified in nasopharyngeal specimens of two cases of severe acute flaccid myelitis. The cases were six and five years-old and occurred in September and November 2014. EV-D68 is increasingly associated with acute flaccid myelitis in children, most cases being reported in the United States. Awareness of this possible neurological complication of enterovirus D68 infection is needed.

IMPETUS Stroke: Assessment of hospital infrastructure and workflow for implementation of uniform stroke care pathway in India.

BACKGROUND: India accounts for 13.3% of global disability-adjusted life years (DALYs) lost due to stroke with a relatively younger age of onset compared to the Western population. In India's public healthcare system, many stroke patients seek care at tertiary-level government-funded medical colleges where an optimal level of stroke care is expected. However, there are no studies from India that have assessed the quality of stroke care, including infrastructure, imaging facilities, or the availability of stroke care units in medical colleges. AIM: This study aimed to understand the existing protocols and management of acute stroke care across 22 medical colleges in India, as part of the baseline assessment of the ongoing IMPETUS stroke study. METHODS: A semi-structured quantitative pre-tested questionnaire, developed based on review of literature and expert discussion, was mailed to 22 participating sites of the IMPETUS stroke study. The questionnaire assessed comprehensively all components of stroke care, including human resources, emergency system, in-hospital care, and secondary prevention. A descriptive analysis of their status was undertaken. RESULTS: In the emergency services, limited stroke helpline numbers, 3/22 (14%); prenotification system, 5/22 (23%); and stroke-trained physicians were available, 6/22 (27%). One-third of hospitals did not have on-call neurologists. Although non-contrast computed tomography (NCCT) was always available, 39% of hospitals were not doing computed tomography (CT) angiography and 13/22 (59%) were not doing magnetic resonance imaging (MRI) after routine working hours. Intravenous thrombolysis was being done in 20/22 (91%) hospitals, but 36% of hospitals did not provide it free of cost. Endovascular therapy was available only in 6/22 (27%) hospitals. The study highlighted the scarcity of multidisciplinary stroke teams, 8/22 (36%), and stroke units, 7/22 (32%). Lifesaving surgeries like hematoma evacuation, 11/22 (50%), and decompressive craniectomy, 9/22 (41%), were performed in limited numbers. The availability of occupational therapists, speech therapists, and cognitive rehabilitation was minimal. CONCLUSION: This study highlighted the current status of acute stroke management in publicly funded tertiary care hospitals. Lack of prenotification, limited number of stroke-trained physicians and neurosurgeons, relatively lesser provision of free thrombolytic agents, limited stroke units, and lack of rehabilitation services are areas needing urgent attention by policymakers and creation of sustainable education models for uniform stroke care by medical professionals across the country.

The effect of vildagliptin relative to sulphonylureas in Muslim patients with type 2 diabetes fasting during Ramadan: the VIRTUE study.

AIMS: To assess, in a real-world setting, the effect of vildagliptin compared with sulphonylurea (SU) treatment on hypoglycaemia in Muslim patients with type 2 diabetes mellitus (T2DM) fasting during Ramadan. METHODS: This multinational, non-interventional study, conducted in Asia and the Middle East, included Muslim adult patients with T2DM who received treatment with vildagliptin or SU as add-on to metformin or monotherapy. During a ~16-week observation period, data were collected up to 6 weeks before and 6 weeks after Ramadan fasting. The primary study objective was to compare the proportion of patients with ≥ 1 hypoglycaemic event (HE) during fasting. RESULTS: Of > 1300 patients enrolled in the study, 684 were treated with vildagliptin and 631 with SUs. Significantly fewer patients experienced ≥ 1 HE with vildagliptin compared with those receiving SUs (5.4% vs. 19.8%, respectively; p < 0.001); no vildagliptin-treated patients reported a grade 2 HE, vs. 4 SU-treated patients (p = 0.053). Mean HbA1c changes from baseline were vildagliptin: -0.24%, SUs: +0.02% (p < 0.001). Mean body weight reductions from baseline were vildagliptin: -0.76 kg, SUs: -0.13 kg (p < 0.001). A higher proportion of SU-treated patients experienced adverse events (AEs) compared with vildagliptin (22.8% vs. 10.2%). This difference was driven by hypoglycaemia as the most common AE. CONCLUSIONS: In this real-world study of fasting Muslim patients with T2DM, vildagliptin was associated with significantly fewer hypoglycaemic episodes compared with SU therapy. This outcome is particularly meaningful when viewed in the context of good glycaemic and weight control observed in vildagliptin-treated patients. Vildagliptin was well tolerated in this patient population.

Scientific advisory on nocturnal hypoglycemia in insulin-treated patients with diabetes: Recommendations from Indian experts.

INTRODUCTION: Insulin is one of the commonly prescribed glucose lowering agents in diabetes. Hypoglycemia is the most common complication, and severe hypoglycemia is the most serious complication of insulin therapy. Almost half of all severe hypoglycemia episodes (HEs) occur at night. However, patients are often unaware of their nocturnal hypoglycaemia (NH) risk. Additionally, both healthcare professionals and patients find it difficult to manage NH. The purpose of this expert group meeting is to improve NH awareness and provide guidance for the physicians to recognize and manage NH. METHOD: The panel of experts in an e-board deliberated extensively upon the available literature and guidelines on hypoglycemia and NH discussed the consensus on definition, detection, reporting, monitoring, treatment, and optimization of therapy in NH. RESULT: & Conclusion: Though there are many guidelines on the management of HEs in patients with diabetes, very few touch the topic of NH. This scientific advisory on management of NH in insulin treated patients with diabetes is formulated to address this gap in understanding regarding management of NH. The experts provide recommendations for the nocturnal window, defining NH based on blood glucose values, recognition, prevention and management of NH.

Evaluating the Impact of Nitrogen Application on Growth and Productivity of Maize Under Control Conditions.

Climatic conditions significantly affect the maize productivity. Among abiotic factors, nitrogen (N) fertilizer and temperature are the two important factors which dominantly affect the maize (Zea mays L.) production during the early crop growth stages. Two experiments were conducted to determine the impact of N fertilizer and temperature on the maize growth and yield. In the first experiment, the maize hybrids were screened for their sensitivity to temperature variations. The screening was based on the growth performance of the hybrids under three temperatures (T 1 = ambient open-air temperature, T 2 = 1°C higher than the ambient temperature, and T 3 = 1°C lower than the ambient temperature) range. The results showed that an increase in temperature was resulted less 50% emergence and mean emergence (4.1 and 6.3 days, respectively), while emergence energy and full emergence were higher (25.4 and 75.2%, respectively) under the higher temperature exposure. The results showed that Syngenta 7720 and Muqabla S 25W87 were temperature tolerant and sensitive maize hybrids, respectively. The second experiment was carried out to study the response of the two selected maize hybrids (Syngenta 7720 and Muqabla S 25W87) to four N fertilizer applications. The results revealed that the maximum N use efficiency (19.5 kg kg-1) was achieved in maize hybrids with low N application (75 kg N ha-1 equivalent to 1.13 g N plant-1). However, the maximum maize grain yield (86.4 g plant-1), dry weight (203 g plant-1), and grain protein content (15.0%) were observed in maize hybrids that were grown with the application of 300 kg N ha-1 (equivalent to 4.52 g N plant-1). Therefore, it is recommended that the application of 300 kg N ha-1 to temperature tolerant maize hybrid may be considered best agricultural management practices for obtaining optimum maize grain yield under present changing climate.

Hippocampal granule cells opt for early retirement.

Increased excitability and plasticity of adult-generated hippocampal granule cells during a critical period suggests that they may "orthogonalize" memories according to time. One version of this "temporal tag" hypothesis suggests that young granule cells are particularly responsive during a specific time period after their genesis, allowing them to play a significant role in sculpting CA3 representations, after which they become much less responsive to any input. An alternative possibility is that the granule cells active during their window of increased plasticity, and excitability become selectively tuned to events that occurred during that time and participate in later reinstatement of those experiences, to the exclusion of other cells. To discriminate between these possibilities, rats were exposed to different environments at different times over many weeks, and cell activation was subsequently assessed during a single session in which all environments were revisited. Dispersing the initial experiences in time did not lead to the increase in total recruitment at reinstatement time predicted by the selective tuning hypothesis. The data indicate that, during a given time frame, only a very small number of granule cells participate in many experiences, with most not participating significantly in any. Based on these and previous data, the small excitable population of granule cells probably correspond to the most recently generated cells. It appears that, rather than contributing to the recollection of long past events, most granule cells, possibly 90-95%, are effectively "retired." If granule cells indeed sculpt CA3 representations (which remains to be shown), then a possible consequence of having a new set of granule cells participate when old memories are reinstated is that new representations of these experiences might be generated in CA3. Whatever the case, the present data may be interpreted to undermine the standard "orthogonalizer" theory of the role of the dentate gyrus in memory.

Unravelling the utility of modern sulfonylureas from cardiovascular outcome trials and landmark trials: expert opinion from an international panel.

AIM: The primary objective of this review is to develop practice-based expert group opinions on the cardiovascular (CV) safety and utility of modern sulfonylureas (SUs) in cardiovascular outcome trials (CVOTs). BACKGROUND: The United States Food and Drug Administration issued new guidance to the pharmaceutical industry in 2008 regarding the development of new antihyperglycemic drugs. The guidance expanded the scope for the approval of novel antihyperglycemic drugs by mandating CVOTs for safety. A few long-term CVOTs on dipeptidyl peptidase 4 inhibitors, glucagon-like peptide 1 receptor agonists, and sodium-glucose cotransporter 2 inhibitors have been completed, while others are ongoing. SUs, which constitute one of the key antihyperglycemic agents used for the management of type 2 diabetes mellitus (T2DM), have been used as comparator agents in several CVOTs. However, the need for CVOTs on modern SUs remains debatable. In this context, a multinational group of endocrinologists convened for a meeting and discussed the need for CVOTs of modern SUs to evaluate their utility in the management of patients with T2DM. At the meeting, CVOTs of modern SUs conducted to date and the hypotheses derived from the results of these trials were discussed. REVIEW RESULTS: The expert group analyzed the key trials emphasizing the CV safety of modern SUs and also reviewed the results of various CVOTs in which modern SUs were used as comparators. Based on literature evidence and individual clinical insights, the expert group opined that modern SUs are cardiosafe and that since they have been used as comparators in other CVOTs, CVOTs of SUs are not required. CONCLUSION: Modern SUs can be considered a cardiosafe option for the management of patients with diabetes mellitus and CV disease; thus CVOTs among individuals with T2DM are not required.

Non-alcoholic fatty liver disease (NAFLD)--the hepatic component of metabolic syndrome.

AIMS: To study the prevalence of NAFLD in those patients attending the routine health checkup and to establish a relationship between NAFLD and metabolic syndrome. PATIENTS AND METHODS: All patients attending the health check-up had their blood pressure, height and weight, waist circumference measurements, blood sugars, lipid levels and ultrasound abdomen done. The prevalence of NAFLD among these subjects was determined and the presence of risk factors for metabolic disease in each individual was analysed. A relationship between NAFLD and metabolic syndrome was then established. RESULTS: Of the 1003 people 225 (22.6%) had NAFLD with higher prevalence among males 164/565 (29%) than among females 61/438 (13.9%). In the NAFLD group normal body mass index (BMI) was present in only 49/225 (20%) of the subjects while 119/225 (52.8%) were overweight and 56/225 (24.8%) were obese. Though liver enzymes were normal the mean AST among cases was 37.41 +/- 14.50 and 33.93 +/- 14.15 among controls and the mean ALT was 38.74 +/- 17.96 among cases and 31.62 +/- 13.49 among controls. Prevalence of metabolic syndrome was 106/225 (47%) among cases and 179/778 (23%) among controls. CONCLUSION: A diagnosis of fatty liver on ultrasound in an asymptomatic person should alert us of metabolic syndrome and its progression to cardiovascular disease. NAFLD may be considered as the hepatic component of metabolic syndrome.

Developing indicators for evaluation of age-friendly communities in Canada: process and results. / Élaboration d'indicateurs pour l'évaluation des collectivités-amies des aînés au Canada : démarche et résultats.

INTRODUCTION: In 2006, the World Health Organization launched the Global Age-Friendly Cities Project to support active aging. Canada has a large number of age-friendly initiatives; however, little is known about the effectiveness and outcomes of age-friendly community (AFC) initiatives. In addition, stakeholders report that they lack the capacity and tools to develop and conduct evaluations of their AFC initiatives. In order to address these gaps, the Public Health Agency of Canada developed indicators to support the evaluation of AFC initiatives relevant to a wide range of Canadian communities. These indicators meet the varied needs of communities, but are not designed to evaluate collective impact or enable crosscommunity comparisons. METHODS: An evidence-based, iterative consultation approach was used to develop indicators for AFCs. This involved a literature review and an environmental scan. Two rounds of key expert and stakeholder consultations were conducted to rate potential indicators according to their importance, actionability and feasibility. A final list of indicators and potential measures were developed based on results from these consultations, as well as key policy considerations. RESULTS: Thirty-nine indicators emerged across eight AFC domains plus four indicators related to long-term health and social outcomes. All meet the intended purpose of evaluating AFC initiatives at the community level. A user-friendly guide is available to support and share this work. CONCLUSION: The AFC indicators can help communities evaluate age-friendly initiatives, which is the final step in completing a cycle of the Pan-Canadian AFC milestones. Communities are encouraged to use the evaluation results to improve their AFC initiatives, thereby benefiting a broad range of Canadians.

INTRODUCTION: En 2006, l'Organisation mondiale de la Santé (OMS) a lancé le projet mondial « Villes-amies des aînés ¼ afin de favoriser un vieillissement actif. Si un grand nombre d'initiatives « amies des aînés ¼ ont été mises en oeuvre au Canada, on dispose de peu d'information sur l'efficacité et les résultats des initiatives des collectivités-amies des aînés (CAA). En outre, les intervenants affirment qu'ils n'ont pas la capacité et les outils nécessaires pour élaborer et réaliser des évaluations relatives à leurs initiatives de CAA. Afin de pallier ces lacunes, l'Agence de la santé publique du Canada a mis au point des indicateurs pour l'évaluation des initiatives de CAA dans de nombreuses collectivités canadiennes. Ces indicateurs, destinés à répondre aux différents besoins des collectivités, ne sont pas conçus pour faire l'évaluation de répercussions collectives ou pour rendre possible une comparaison entre collectivités. MÉTHODOLOGIE: Une démarche de consultation itérative fondée sur des données probantes a été employée pour l'élaboration d'indicateurs relatifs aux CAA. Elle a nécessité une revue de la littérature et une analyse du contexte. Deux rondes de consultation auprès d'experts et d'intervenants clés ont été menées, ce qui a permis de classer les indicateurs potentiels en fonction de leur importance, de leur capacité à être mis en pratique et de leur faisabilité. Une liste définitive d'indicateurs et de mesures potentielles a ensuite été mise au point, en fonction des résultats de ces consultations et de considérations clés relatives aux politiques. RÉSULTATS: Trente-neuf indicateurs répartis en huit domaines relevant des CAA et quatre indicateurs relevant des résultats liés à la santé et aux conditions sociales à long terme ont été sélectionnés. Tous sont conformes à l'objectif énoncé, à savoir l'évaluation des initiatives de CAA à l'échelon local. Un guide convivial est disponible pour soutenir et diffuser ce travail. CONCLUSION: Les indicateurs de CAA sont susceptibles d'aider les collectivités à procéder à l'évaluation de leurs initiatives amies des aînés, ce qui constitue la dernière étape du cycle des jalons pancanadiens des CAA. Les collectivités sont en effet encouragées à améliorer leurs initiatives amies des aînés à partir de l'évaluation de leurs résultats, afin d'en faire profiter un large éventail de Canadiens.

Independence of firing correlates of anatomically proximate hippocampal pyramidal cells.

In neocortex, neighboring neurons frequently exhibit correlated encoding properties. There is conflicting evidence whether a similar phenomenon occurs in hippocampus. To assess this quantitatively, a comparison was made of the spatial and temporal firing correlations within and between local groups of hippocampal cells, spaced 350-1400 microm apart. No evidence of clustering was found in a sample of >3000 neurons. Moreover, cells active in two environments were uniformly interspersed at a scale of <100 microm, as assessed by the activity-induced gene Arc. Independence of encoding characteristics implies uncorrelated inputs, which could enhance the capacity of the hippocampus to store arbitrary associations.

Thrombomodulin overexpression to limit neointima formation.

BACKGROUND-These studies were initiated to confirm that high-level thrombomodulin overexpression is sufficient to limit neointima formation after mechanical overdilation injury. METHODS AND RESULTS-An adenoviral construct expressing thrombomodulin (Adv/RSV-THM) was created and functionally characterized in vitro and in vivo. The impact of local overexpression of thrombomodulin on neointima formation 28 days after mechanical overdilation injury was evaluated. New Zealand White rabbit common femoral arteries were treated with buffer, viral control, or Adv/RSV-THM and subjected to mechanical overdilation injury. The treated vessels (n=4 per treatment) were harvested after 28 days and evaluated to determine intima-to-media (I/M) ratios. Additional experiments were performed to determine early (7-day) changes in extracellular elastin and collagen content; local macrophage, T-cell, and neutrophil infiltration; and local thrombus formation as potential contributors to the observed impact on 28-day neointima formation. The construct significantly decreased neointima formation after mechanical dilation injury in this model. By histological analysis, buffer controls exhibited mean I/M ratios of 0.76+/-0.06%, whereas viral controls reached 0.77+/-0.08%; in contrast, Adv/RSV-THM reduced I/M ratios to 0.47+/-0.06%. Local inflammatory infiltrate decreased in the Adv/RSV-THM group relative to controls, whereas matrix remained relatively preserved. Rates of early thrombus formation also decreased in Adv/RSV-THM animals. CONCLUSIONS-This construct thus offers a viable technique for promoting a locally neointima-resistant small-caliber artery via decreased thrombus bulk, normal matrix preservation, and decreased local inflammation without the inflammatory damage that has limited many other adenoviral applications.

Designer insulins regimens in clinical practice--pilot multicenter Indian study.

BACKGROUND: Newer insulin analogues viz., premix insulin analogue (biphasic insulin aspart) and insulin glargine are now available in India. A multicenter all-India study was done to document the patient profile and responses to these analogues in routine clinical practice. METHODS: The study was conducted prospectively at 4 diabetes care clinics in different regions of India and collected data on the use of either of the two regimens A. Premix insulin analogue given twice-daily B. Basal-bolus analogue regimen (insulin aspart with every meal and insulin glargine once-a-day at bedtime). The centers collected all data at 3 time-points--baseline, 4 weeks later and end of 12 weeks. The study measures were FPG (fasting plasma glucose), PPPG (postprandial plasma glucose), HbA1c and insulin dose. FPG and PPPG were recorded at each of the three time points. HbA1c was recorded at baseline and end of study. Safety was assessed based on reported adverse drug reactions and occurrence of hypoglycaemias. RESULTS: Data of 145 patients was available for analysis (n=114 on premix insulin analogue and n=31 on basal-bolus analogue regimen). Baseline demography was comparable in the two groups. Both the regimens lowered all blood glucose parameters including HbA1c significantly as compared to baseline. However, the premix insulin analogue fared better than the basal-bolus regimen in lowering HbA1c (1.58 vs. 1.16% respectively; p<0.05). Also 41% more patients in the premix group could achieve target HbA1c of < 7% at the end of study. The mean insulin dose was lower with the premix analogue group at the end of 12 weeks. There was no significant difference between the two groups in terms of change in body weight. No major hypoglycaemias were reported and the percentage of patients experiencing a minor episode was lower with the premix analogue than the basal-bolus regimen both at 4 and 12 weeks (11.4 vs. 35.48%; 16.7 vs. 58.06% respectively). No adverse drug reactions were reported throughout the study. CONCLUSION: We conclude that both premix analogue administered twice a day and four times a day basal bolus regimen appear to be a convenient, safe and effective way of initiating insulin therapy in people with type-2 diabetes. The premix analogues achieves target better than the basal bolus regimen as has better compliance.

Localization of neurons expressing substance P and neurokinin B gene transcripts in the human hypothalamus and basal forebrain.

In situ hybridization histochemistry was used to map the distribution of neurons expressing the substance P (SP) or neurokinin B (NKB) genes in the human hypothalamus and basal forebrain. Hypothalami from five adult males were frozen in isopentane at -30 degrees C and serially sectioned at 20 jm thickness. Every 20th section was hybridized with [35S]-labeled, 48-base synthetic cDNA probes that were complementary to either SP or NKB mRNAs. Slides were dipped into nuclear emulsion for visualization of mRNAs at the single-cell level. The location of labeled neurons (greater than x 5 background) was mapped by using an image-combining computer microscope system. A distinct and complementary distribution pattern of SP and NKB neurons was observed in the human hypothalamus and basal forebrain. NKB was the predominant tachykinin in the rostral hypothalamus, whereas SP mRNA predominated in the posterior hypothalamus. Numerous NKB neurons were identified in the magnocellular basal forebrain, the bed nucleus of stria terminalis, and the anterior hypothalamic area. Scattered NKB neurons were present in the infundibular and paraventricular nuclei, paraolfactory gyrus, posterior hypothalamic area, lateral division of the medial mammillary nucleus, and amygdala. Numerous neurons expressing SP mRNAs were identified in the premammillary, supramammillary, and medial mammillary nuclei; the posterior hypothalamic area; and the corpus striatum. Scattered SP neurons were also observed in the preoptic area; the infundibular, intermediate, dorsomedial, and ventromedial nuclei; the infundibular stalk; the amygdala; the bed nucleus of stria terminalis; and the paraolfactory gyrus. These studies provide the first description of the location of neurons that express tachykinin gene transcripts in the human hypothalamus.

Signal dynamics in magnetic resonance imaging of the lung with hyperpolarized noble gases.

The nonequilibrium bulk magnetic moment of hyperpolarized (HP) noble gases generated by optical pumping has unique characteristics. Based on the Bloch equations, a model was developed describing the signal dynamics of HP gases used in magnetic resonance imaging (MRI) of the lung with special consideration to the breathing cycle. Experimental verification included extensive investigations with HP 3He and 129Xe during both inspiration and held breath in live guinea pigs. Radial acquisition was used to investigate the view variations with a temporal resolution of 5 ms. Agreement between theoretical predictions and in vivo results was excellent. Additionally, information about effects from noble gas diffusion and spin-lattice relaxation was obtained. In vivo results for T1 were 28.8 +/- 1.8 s for 3He and 31.3 +/- 1.8 s for 129Xe. Comparison with in vitro data indicated that relaxation in the pulmonary gas space is dominated by dipolar coupling with molecular oxygen. The results provide a quantitative basis for optimizing pulse sequence design in HP gas MRI of the lung.