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La mortalité néonatale est élevée en Côte d’Ivoire. L’objectif était d’évaluer les structures sanitaires publiques prenant en charge le nouveau-né dans la commune de Yopougon Abidjan, en Côte d’Ivoire. Nous avons effectué une étude prospective à visée descriptive portant sur l’analyse des types, des locaux, du personnel, du matériel des structures sanitaires disposant d’une maternité. Les structures ont été évaluées selon les normes françaises et ivoiriennes. Cette étude s’est déroulée de septembre à octobre 2013. La commune de Yopougon comporte 19 structures sanitaires publiques disposant d’une maternité. Elle est composée de 17 établissements sanitaires de premier contact (ESPC), 1 hôpital général (HG) et 1 centre hospitalier universitaire (CHU). Le ratio population/structures sanitaires était loin de la norme. Le CHU était classé en niveau IIa selon les normes françaises de niveau de maternité, une seule structure sanitaire publique disposait d’un service d’hospitalisation néonatale. Le personnel des ESPC et de l’HG était insuffisant, composé de 2,4 % de pédiatres, de 3,4 % de gynéco-obstétriciens, de 43 % de sages-femmes et de 29,4 % d’aides-soignantes selon les normes françaises et ivoiriennes. Il n’y avait pas de source à oxygène dans 68,4 % des structures sanitaires, 94,7 % n’avaient pas d’insufflateur manuel, et 26,3 % n’avaient pas d’aspirateur électrique, rendant les gestes de réanimation néonatale difficilement envisageables. L’évaluation des structures sanitaires publiques de la commune de Yopougon montre des insuffisances au niveau des locaux, du personnel et du matériel, rendant difficile la prise en charge du nouveau-né. Neonatal mortality is high in the Ivory Coast. The objective was to evaluate the public health facilities available for caring for neonates in the Yopougon- Abidjan commune in the Ivory Coast. We have carried out a prospective descriptive study, based on an analysis of the types, buildings, staff and equipment in the healthcare facilities that have a maternity department. The facilities were evaluated according to both French and Ivory Coast standards. This study was conducted between September and October 2013. The Yopougon commune has 19 public healthcare facilities that have a maternity department. These include 17 initial contact healthcare facilities (ICHF), 1 general hospital (GH) and 1 university hospital centre (UHC). The ratio of people to healthcare facility was far from the norm. The UHC was classified as a level IIa according to French maternity standards, as the only public healthcare facility to have a neonatal admissions department. The staffing levels at the ICHF and the GH were inadequate, comprising 2.4% paediatricians, 3.4% gynaecologists and obstetricians, 43% midwives and 29.4% healthcare assistants, based on French and Ivory Coast standards. There were no sources of oxygen in 68.4% of the healthcare facilities, 94.7% did not have a manual resuscitator and 26.3% did not have an electrical suction pump, making neonatal resuscitation procedures barely possible. The evaluation of the public health facilities in the Yopougon commune shows that there are inadequacies in terms of the premises, staffing and equipment, making caring for neonates very difficult.

Although clinical reports have highlighted association of the deacetylase sirtuin1 (SIRT1) gene with anxiety, its exact role in the pathogenesis of anxiety disorders remains unclear. The present study was designed to explore whether and how SIRT1 in the mouse bed nucleus of the stria terminalis (BNST), a key limbic hub region, regulates anxiety. In a chronic stress model to induce anxiety in male mice, we used site- and cell-type-specific in vivo and in vitro manipulations, protein analysis, electrophysiological and behavioral analysis, in vivo MiniScope calcium imaging and mass spectroscopy, to characterize possible mechanism underlying a novel anxiolytic role for SIRT1 in the BNST. Specifically, decreased SIRT1 in parallel with increased corticotropin-releasing factor (CRF) expression was found in the BNST of anxiety model mice, whereas pharmacological activation or local overexpression of SIRT1 in the BNST reversed chronic stress-induced anxiety-like behaviors, downregulated CRF upregulation, and normalized CRF neuronal hyperactivity. Mechanistically, SIRT1 enhanced glucocorticoid receptor (GR)-mediated CRF transcriptional repression through directly interacting with and deacetylating the GR co-chaperone FKBP5 to induce its dissociation from the GR, ultimately downregulating CRF. Together, this study unravels an important cellular and molecular mechanism highlighting an anxiolytic role for SIRT1 in the mouse BNST, which may open up new therapeutic avenues for treating stress-related anxiety disorders.

Exercise intolerance is an important impairment in patients with SMA, but little is known about the mechanisms underlying this symptom. To investigate if reduced motor unit and capillary recruitment capacity in patients with SMA contribute to exercise intolerance. Adolescent and adult patients with SMA types 3 and 4 (n = 15) and age- and gender matched controls (n = 15) performed a maximal upper body exercise test. We applied respiratory gas analyses, non-invasive surface electromyography (sEMG) and continuous wave near-infrared spectroscopy (CW-NIRS) to study oxygen consumption, arm muscle motor unit- and capillary recruitment, respectively. Maximal exercise duration was twofold lower (p < 0.001) and work of breathing and ventilation was 1.6- and 1.8-fold higher (p < 0.05) in patients compared to controls, respectively. Regarding motor unit recruitment, we found higher normalized RMS amplitude onset values of sEMG signals from all muscles and the increase in normalized RMS amplitudes was similar in the m. triceps brachii, m. brachioradialisand m. flexor digitorumin SMA compared to controls. Median frequency, onset values were similar in patients and controls. We found a similar decrease in median frequencies of sEMG recordings from the m. biceps brachii, a diminished decrease from the m. brachioradialisand m. flexor digitorum,but a larger decrease from the m. triceps brachii. With respect to capillary recruitment, CW-NIRS recordings in m. biceps brachiirevealed dynamics that were both qualitatively and quantitatively similar in patients and controls. We found no evidence for the contribution of motor unit and capillary recruitment capacity of the upper arm muscles in adolescent and adult patients with SMA types 3 and 4 as primary limiting factors to premature fatigue during execution of a maximal arm-cycling task.

AbstractNeighbours have been found to influence each other’s behaviour (contagion effect). However, little is known about the influence on sport club membership. This while increasing interest has risen for the social role of sport clubs. Sport clubs could bring people from different backgrounds together. A mixed composition is a key element in this social role. Individual characteristics are strong predictors of sport club membership. Western high educated men are more likely to be members. In contrast to people with a non-Western migration background. The neighbourhood is a more fixed meeting place, which provides unique opportunities for people from different backgrounds to interact. This study aims to gain more insight into the influence of neighbours on sport club membership. This research looks especially at the composition of neighbour’s migration background, since they tend to be more or less likely to be members and therefore could encourage of inhibit each other. A population database including the only registry data of all Dutch inhabitants was merged with data of 11 sport unions. The results show a cross-level effect of neighbours on sport club membership. We find a contagion effect of neighbours’ migration background; having a larger proportion of neighbours with a migration background from a non-Western country reduces the odds, as expected. However, this contagion effect was not found for people with a Moroccan or Turkish background.

Worldwide usage of plywood, the original engineered wood panel, has continued to grow, However, North American plywood production and consumption has finally stabilized (2012–2016) after steadily declining since the 1987 peak. The decline was particularly sharp from 2007 to 2009 during the years of the Great Recession.

Context:Since the discovery of its central role in reproduction, our functional neuroanatomical knowledge of the hypothalamic kisspeptin system is predominantly based on animal studies. Although sex differences in kisspeptin expression have been shown in humans in adulthood, the developmental origin of this sex difference is unknown.Objectives:Our objectives were to determine the following: 1) when during development the sex difference in kisspeptin expression in the infundibular nucleus would emerge and 2) whether this sex difference is related to sexual orientation or transsexuality.Design and Setting:Postmortem hypothalamic tissues were collected by The Netherlands Brain Bank, and sections were stained for kisspeptin by immunohistochemistry.Patients:Hypothalami of 43 control subjects were categorized into three periods: infant/prepubertal (six girls, seven boys), adult (11 women, seven men), and elderly (six aged women, six aged men). Eight male-to-female (MTF) transsexuals, three HIV+heterosexual men, and five HIV+homosexual men were also analyzed.Main Outcome Measure:We estimated the total number of kisspeptin-immunoreactive neurons within the infundibular nucleus.Results:Quantitative analysis confirmed that the human infundibular kisspeptin system exhibits a female-dominant sex difference. The number of kisspeptin neurons is significantly greater in the infant/prepubertal and elderly periods compared with the adult period. Finally, in MTF transsexuals, but not homosexual men, a female-typical kisspeptin expression was observed.Conclusions:These findings suggest that infundibular kisspeptin neurons are sensitive to circulating sex steroid hormones throughout life and that the sex reversal observed in MTF transsexuals might reflect, at least partially, an atypical brain sexual differentiation.

Context:Glucagon-like peptide-1 (GLP-1) and GLP-1 receptor agonist treatment in type 2 diabetes (T2DM) reduce blood glucose and food intake. It has been suggested that these effects are partly mediated through central GLP-1 receptors (GLP-1Rs). The rodent and nonhuman primate hypothalamus show clear GLP-1R expression. However, a detailed description of GLP-1R expression in the human hypothalamus is lacking, and it is unknown whether this expression is altered in T2DM patients.Objective:The objective of the study was to investigate the GLP-1R distribution in the human postmortem hypothalamus and to determine whether hypothalamic GLP-1R expression is altered in T2DM patients.Design:We investigated the distribution of GLP-1R expression throughout the human hypothalamus by means of in situ hybridization. We also performed quantifications of GLP-1R mRNA expression in two hypothalamic nuclei (ie, the paraventricular nucleus [PVN] and infundibular nucleus [IFN]), comparing patients with T2DM and control subjects.Results:We found that GLP-1R mRNA was expressed in a number of hypothalamic nuclei including the PVN and the IFN, both involved in the regulation of energy metabolism. We observed sporadic colocalization of the GLP-1R in the IFN with the orgexigenic neuropeptide Y, agouti-related peptide, or proopiomelanocortin transcripts. Comparison of GLP-1R mRNA in the PVN and IFN between T2DM patients and control subjects revealed a decreased expression in T2DM patients.Conclusions:Our studies show that GLP-1R is widely expressed throughout the human hypothalamus. The decreased expression of GLP-1R in the PVN and IFN of T2DM patients may be related to the dysregulation of feeding behavior and glucose homeostasis in T2DM.

To study whether sleep and circadian rhythm disturbances in patients with Huntington's disease (HD) arise from dysfunction of the body's master clock, the hypothalamic suprachiasmatic nucleus.

Patients with critical limb ischaemia (CLI) are usually elderly and suffer from several co-morbidities. The goal of surveillance after both endovascular and surgical revascularization for CLI is not only the protection of re-established distal perfusion and sustained ambulation but also the reduction of systemic atherothrombotic risk and mortality by ensuring continued best medical care. However, preferred format and rhythm of structured follow-up programs have remained controversial, mainly because of lack of compelling evidence. This review aims to summarize and to appraise available information critically. Thereby, it underlines the importance of systematic surveillance after both surgical and endovascular revascularization for CLI. Recent European guidelines are considered and areas of uncertainty are highlighted and discussed. According to currently available literature and recent guidelines, the early duplex scan is justified in all patients undergoing endovascular or surgical distal revascularization for CLI. There is no best level evidence supporting continued long term duplex surveillance of revascularizations with normal findings at early duplex scan, whereas those patients with abnormal early duplex scan or high risk revacularization are likely to benefit from continued duplex surveillance. Regular clinical follow-up is suggested and clinical deterioration should trigger duplex scanning to ensure revascularization patency.

Surface EMG comprises a variety of widely applied experimental tools in basic neuroscience, biomechanics and exercise physiology, but also in applied disciplines like clinical neuro-physiology, ergonomics and sports sciences. To increase the usefulness of surface EMG, we contributed to the introduction and application of a spatiotemporal variant of the usual single channel surface EMG techniques, called high-density surface EMG (HD-sEMG). In the present paper, we first discuss the background of the HD-sEMG technique and basic principles of recording and analysis. In a second part, we illustrate the usefulness of the technique on the basis of studies in which the analysis of HD-sEMG at a motor unit level is at hand. It concerns a precise analysis of the activity of the facial musculature that leads to a map of muscle fibre directions and the positions of motor endplate zones. Two other applications refer to neuromuscular pathology, being motor unit number estimation and the quantification of spontaneous motor unit activity, known as fasciculations.

Background and Aims: Two thirds of patients with an abdominal aortic aneurysm (AAA) have relevant coronary artery disease (CAD). AAAs are prevalent in up to 16% of smokers with CAD. General screening of AAA is controversial. Aim was to assess the potential of finding AAA prior to rupture among patients with known CAD. Main endpoint was whether AAA could have been found during follow-up by sonography or at other time of cardiovascular evaluation.Material and Methods: Retrospective study. 213 consecutive, formerly unknown emergently operated AAAs, treated emergently for symptoms (n = 91) or rupture (n = 122) (rAAA) between January 1998 and June 2005. Patient charts were analysed and primary care physicians contacted.Results: At presentation, mean age was 71 (+/–9) years, twenty (9%) were female. AAA had a mean diameter of 7.6 cm. Two thirds (143) were clinically obese (BMI 27 +/–5). 137 (64%) were active smokers, 32 (15%) had diabetes, 151 (71%) were hypertensive, and 80 (38%) received statin treatment. CAD had been diagnosed in 95 (45%) 9 years earlier and followed up. Thirty-five (16%) had had myocardial infarction. Echocardiography had been performed in 52 (24%). Thirty day mortality after open surgery was 25 (21%).Conclusion: All patients with rAAA had been seen by a GP or cardiologist within a year prior to presentation. The cost effectiveness of selective AAA screening should be evaluated in a larger study.

Representations of different body parts or muscles in the human primary motor cortex overlap extensively. At the effector level, most muscles are surrounded by and overlap with several neighbours as well. This hampers the assessment of excitability in individual muscles with transcranial magnetic stimulation (TMS), even if so-called “focal” stimulating coils are used. Here we used a novel mapping paradigm based on high-density surface electromyography (HD-sEMG) to investigate the spatial selectivity of TMS in the forearm musculature. In addition, we tested the hypothesis that selective stimulation can be improved by a voluntary background contraction of the target muscle. We mapped and compared the topographies of motor evoked potential (MEP) amplitudes during rest and during background contractions of two forearm muscles (extensor carpi radialis and extensor digitorum communis). The MEP topographies were also compared to the amplitude topography of voluntary EMG. The results indicate that under many conditions a large proportion of the MEP activity recorded at the surface originated from the target muscle's neighbours. There was a systematic relationship between TMS intensity and the topographic distribution of MEP responses during voluntary contraction. With increasing stimulus intensity, the MEP topography deviated increasingly more from the topography of voluntary EMG. We conclude that when standard EMG montages are used, the recorded MEPs are not necessarily evoked in the target muscle alone. Stimulation during a voluntary background contraction of the target muscle may enhance the selectivity of TMS. It however remains essential to use stimulus intensities as low as possible, to minimize the contribution of surrounding non-target muscles to the MEP.

In amyotrophic lateral sclerosis (ALS), the origin of fasciculations is disputed. We hypothesized that the discharge pattern of fasciculation potentials (FPs) would be different for FPs arising in the motor axon or in the spinal motor neuron.

In this review, we summarize and discuss recent studies on structural plasticity changes, particularly apoptosis, in the mammalian hippocampus in relation to stress and depression. Apoptosis continues to occur, yet with very low numbers, in the adult hippocampal dentate gyrus (DG) of various species. Stress and steroid exposure modulate the rate of apoptosis in the DG. Contrary to earlier studies, the impact of chronic stress on structural parameters of the hippocampus like cell number and volume, is rather modest, and requires prolonged and severe stress exposure before only small reductions ( &lt; 10 %) become detectable. This does not exclude other structural parameters, like synaptic terminal structure, or dendritic arborization from being significantly altered in critical hippocampal subregions like the DG and/or CA3. Neither does it imply that the functional implications of the changes after stress are also modest. Of interest, most of the structural plasticity changes appear transient and are generally reversible after appropiate recovery periods, or following cessation or blockade of the stress or corticosteroid exposure. The temporary slowing down of both apoptosis and adult proliferation, i.e. the DG turnover, after chronic stress will affect the overall composition, average age and identity of DG cells, and will have considerable consequences for the connectivity, input and properties of the hippocampal circuit and thus for memory function. Modulation of apoptosis and neurogenesis, by drugs interfering with stress components like MR and/or GR, and/or mediators of the cell death cascade, may therefore provide important drug targets for the modulation of mood and memory.

Objective: An increasing number of proteins appear to be involved in thyroid hormone feedback action at the level of the anterior pituitary, but the cell types expressing these proteins are largely unknown. The aim of the present study was to identify cell types in the human anterior pituitary that express type II and type III deiodinase (D2 and D3), the recently described thyroid hormone transporter (MCT8) and thyroid hormone receptor (TR) isoforms by means of double-labeling immunocytochemistry.Results: We found TR isoforms to be expressed most prominently in gonadotropes and – although to a lesser extent – in thyrotropes, corticotropes, lactotropes and somatotropes. D3 staining showed a distribution pattern that was remarkably similar. By contrast, D2 immunoreactivity was observed exclusively in folliculostellate (FS) cells showing coexpression with human leukocyte antigen (HLA), a marker of major histocompatibility complex (MHC)-class II. MCT8 immunostaining was present in FS cells without HLA coexpression.Conclusions: From these results, we propose a novel neuroanatomical model for thyroid hormone feedback on the human pituitary, with a central role for FS cells in thyroid hormone activation, which thus play an important role in the suppression of TSH secretion by circulating thyroxine (T4).

OBJECTIVE: An increasing number of proteins appear to be involved in thyroid hormone feedback action at the level of the anterior pituitary, but the cell types expressing these proteins are largely unknown. The aim of the present study was to identify cell types in the human anterior pituitary that express type II and type III deiodinase (D2 and D3), the recently described thyroid hormone transporter (MCT8) and thyroid hormone receptor (TR) isoforms by means of double-labeling immunocytochemistry. RESULTS: We found TR isoforms to be expressed most prominently in gonadotropes and – although to a lesser extent – in thyrotropes, corticotropes, lactotropes and somatotropes. D3 staining showed a distribution pattern that was remarkably similar. By contrast, D2 immunoreactivity was observed exclusively in folliculostellate (FS) cells showing coexpression with human leukocyte antigen (HLA), a marker of major histocompatibility complex (MHC)-class II. MCT8 immunostaining was present in FS cells without HLA coexpression. CONCLUSIONS: From these results, we propose a novel neuroanatomical model for thyroid hormone feedback on the human pituitary, with a central role for FS cells in thyroid hormone activation, which thus play an important role in the suppression of TSH secretion by circulating thyroxine (T4).

Oestrogens may modulate the activity of the hypothalamic–pituitary–adrenal (HPA) axis. The present study was to investigate whether the activity of the HPA axis in mood disorders might be directly modulated by oestrogens via oestrogen receptors (ORs) in the corticotropin-releasing hormone (CRH) neurons of the human hypothalamic paraventricular nucleus (PVN). Brains of 13 subjects ranging in age between 45 and 79 years suffering from major depression/major depressive disorder (eight cases) or bipolar disorder (five cases) and of 13 controls, matched for sex, age, brain weight, post-mortem delay, fixation time and season and clock time at death, were studied with double-label immunocytochemistry. The total number of CRH-immunoreactive (IR) neurons, CRH neurons that colocalized ORα in the neuronal nucleus and the number of only nuclear ORα-containing neurons in the PVN were measured using an image analysis system. In addition, the volume of the PVN delineated on the basis of CRH neurons was determined. It was found that the total number of CRH-IR neurons in patients with mood disorders was nearly 1.7 times higher than in controls (P = 0.034). A novel finding was that the total number of CRH-IR neurons and the number of CRH-nuclear ORα double-staining neurons in the PVN were strongly correlated both in controls and in patients with mood disorders (P < 0.001 and P = 0.022, respectively). The ratio of the CRH-nuclear-ORα double-staining neurons to the total CRH-IR neurons in patients with mood disorders was similar to that in the controls (P = 0.448). The volume of the sub-region of the PVN that was delineated on the basis of CRH neurons was significantly larger in patients with mood disorders than in controls (P = 0.022). Another novel finding was the large population of extra-hypothalamic CRH neurons that was found in the thalamus. In summary, oestrogens may directly influence CRH neurons in the human PVN. The increased numbers of neurons expressing CRH in mood disorders is accompanied by increased ORα colocalization in the nucleus of these neurons. These changes seem to be trait- rather than state-related.

In previous studies, transcutaneous electrical nerve stimulation (TENS) has been applied to patients with either Alzheimer’s disease (AD) or incipient dementia, resulting in an enhancement in memory and verbal fluency. Moreover, affective behavior was shown to improve. Based on the positive effects of TENS in AD, it was hypothesized that TENS would improve self-efficacy in nondemented elderly with mild cognitive impairment (MCI) who live in a residential home. Four outcome measures, that is, a Dutch translation of the General Self-Efficacy Scale (Algemene Competentie Schaal), the Groninger Activity Restriction Scale, the Philadelphia Geriatric Center Morale Scale, and the Geriatric Depression Scale, were administered. Overall, the results suggest that the experimental group showed a mild improvement in self-efficacy and mood. In contrast, the placebo group showed a considerable reduction in self-efficacy and an increase in depression. Limitations of the present study and suggestions for future research are discussed.

In this postmortem study, we investigated the relationship between multiple sclerosis (MS) lesions in the hypothalamus and the state of activity of corticotropin-releasing hormone (CRH)–producing neurons that control the hypothalamus-pituitary-adrenal (HPA) axis. A high incidence (15/16) of MS lesions was found in the hypothalamus, of which more than 50% was active, that is, contained activated macrophages. MS patients have increased numbers of CRH-immunoreactive neurons coexpressing vasopressin (CRH/VP neurons), a sign of chronic activation of CRH neurons and increased CRH mRNA expression. Active MS lesions correlated with a low number of hyperactive CRH/VP neurons. High human leukocyte antigen (HLA)-DR, -DP, -DQ expression, a measure for macrophage and microglial activation, correlated with low CRH mRNA expression. The nearer the HLA expression was situated to the CRH neurons, the stronger the inhibiting effect, suggesting that activated microglial cells or macrophages suppress these neurons. The more active MS lesions were present in the hypothalamus, the shorter was the disease duration until the moment of death, indicating an unfavorable course of the disease. Thus, MS patients have a chronically activated CRH system, but, in the subgroup of patients with active MS lesions in the hypothalamus, this activation is impaired and the disease course is worse.

In this postmortem study, we investigated the relationship between multiple sclerosis (MS) lesions in the hypothalamus and the state of activity of corticotropin‐releasing hormone (CRH)–producing neurons that control the hypothalamus‐pituitary‐adrenal (HPA) axis. A high incidence (15/16) of MS lesions was found in the hypothalamus, of which more than 50% was active, that is, contained activated macrophages. MS patients have increased numbers of CRH‐immunoreactive neurons coexpressing vasopressin (CRH/VP neurons), a sign of chronic activation of CRH neurons and increased CRH mRNA expression. Active MS lesions correlated with a low number of hyperactive CRH/VP neurons. High human leukocyte antigen (HLA)‐DR, ‐DP, ‐DQ expression, a measure for macrophage and microglial activation, correlated with low CRH mRNA expression. The nearer the HLA expression was situated to the CRH neurons, the stronger the inhibiting effect, suggesting that activated microglial cells or macrophages suppress these neurons. The more active MS lesions were present in the hypothalamus, the shorter was the disease duration until the moment of death, indicating an unfavorable course of the disease. Thus, MS patients have a chronically activated CRH system, but, in the subgroup of patients with active MS lesions in the hypothalamus, this activation is impaired and the disease course is worse.

During multiple sclerosis (MS), an inflammatory demyelinating disease of the central nervous system (CNS), activation of the hypothalamo-pituitary-adrenal (HPA) axis is considered to modulate the immune system in such a way that the probability of recovery from a relapse is increased. In a series of postmortem studies we observed a significant activation of corticotropin releasing hormone (CRH) neurons and increased cortisol in the cerebrospinal fluid (CSF) of MS patients, indicating activation of the HPA axis in this disease. On the other hand, sepsis, while elevating cortisol in control subjects, did not associate with a further increase of cortisol in MS patients. Thus, the activated HPA-system in MS does not respond to an acute inflammatory stimulus. In order to investigate the role of chronic inflammation in the CNS in the activation of the HPA axis in MS, MS lesions in the hypothalamus were quantified and interleukin (IL)-6 levels in the CSF were determined. There was no difference in IL-6 levels between MS and control patients. A positive correlation was found between cortisol and IL-6 in control subjects with sepsis, but not in MS patients with sepsis or MS and control groups without sepsis. Thus, IL-6 in the CSF of MS patients is not the cause of the activation of the HPA system in MS. We found a remarkably high incidence (95 of the patients) of MS lesions in the hypothalamus, of which the majority (60) were active. The more active lesions were present in the hypothalamus, the shorter the disease duration to the moment of death, indicative of a worse disease course. Preliminary data show suppression of the activation of CRH neurons by active hypothalamic MS lesions. We propose that this suppression of CRH neurons by active hypothalamic MS lesions causes the concomitant unfavorable disease course via an inadequate cortisol response during relapses of MS.

A variety of Asp β-carboxy protecting groups, Hmb backbone protection and a range of Fmoc cleavage protocols have been employed in syntheses of the model hexapeptide H-VKDGYI-OH to investigate the aspartimide problem in more detail. The extent of formation of aspartimide and aspartimide-related by-products was determined by RP-HPLC. This study included three new Fmoc-Asp-OH derivatives: the β-(4-pyridyl-diphenylmethyl) and β-(9-phenyl-fluoren-9-yl) esters and also the orthoester Fmoc-β-(4-methyl-2,6,7-trioxabicyclo[2.2.2]-oct-1-yl)-alanine. 3-Methylpent-3-yl protection of the Asp side chain resulted in significant improvements with respect to aspartimide formation. Complete suppression was achieved using the combination OtBu side chain protection and Hmb backbone protection for the preceding Gly residue. Copyright © 2003 European Peptide Society and John Wiley & Sons, Ltd.

A variety of Asp β‐carboxy protecting groups, Hmb backbone protection and a range of Fmoc cleavage protocols have been employed in syntheses of the model hexapeptide H‐VKDGYI‐OH to investigate the aspartimide problem in more detail. The extent of formation of aspartimide and aspartimide‐related by‐products was determined by RP‐HPLC. This study included three new Fmoc‐Asp‐OH derivatives: the β‐(4‐pyridyl‐diphenylmethyl) and β‐(9‐phenyl‐fluoren‐9‐yl) esters and also the orthoester Fmoc‐β‐(4‐methyl‐2,6,7‐trioxabicyclo[2.2.2]‐oct‐1‐yl)‐alanine. 3‐Methylpent‐3‐yl protection of the Asp side chain resulted in significant improvements with respect to aspartimide formation. Complete suppression was achieved using the combination OtBu side chain protection and Hmb backbone protection for the preceding Gly residue. Copyright © 2003 European Peptide Society and John Wiley & Sons, Ltd.

The present study reports the first systematic rostrocaudal distribution of estrogen receptor‐α immunoreactivity (ERα‐ir) in the human hypothalamus and its adjacent areas in young adults. Postmortem material taken from 10 subjects (five male and five female), between 20 and 39 years of age, was investigated. In addition, three age‐matched subjects with abnormal levels of estrogens were studied: a castrated, estrogen‐treated 50‐year‐old male‐to‐female transsexual (T1), a 31‐year‐old man with an estrogen‐producing tumor (S2), and an ovariectomized 46‐year‐old woman (S8). A strong sex difference, with more nuclear ERα‐ir in women, was observed rostrally in the diagonal band of Broca and caudally in the medial mamillary nucleus. Less robust sex differences were observed in other brain areas, with more intense nuclear ERα‐ir in men, e.g., in the sexually dimorphic nucleus of the medial preoptic area, paraventricular nucleus, and lateral hypothalamic area, whereas women had more nuclear ERα‐ir in the suprachiasmatic nucleus and ventromedial nucleus. No nuclear sex differences in ERα were found, e.g., in the central part of the bed nucleus of the stria terminalis. In addition to nuclear staining, ERα‐ir appeared to be sex‐dependently present in the cytoplasm of neurons and was observed in astrocytes, plexus choroideus, and other non‐neuronal cells. ERα‐ir in T1, S2, and S8 suggested that most of the observed sex differences in ERα‐ir are “activational” (e.g., ventromedial nucleus/medial mamillary nucleus) rather than “organizational.” Species similarities and differences in ERα‐ir distribution and possible functional implications are discussed. J. Comp. Neurol. 454:115–139, 2002. © 2002 Wiley‐Liss, Inc.

Background: Subtle cognitive and neurological impairments have been found in some workers exposed to organic solvents. Whether these effects occur at or below current legal limits for occupational exposure is controversial.
Aim: To determine whether occupational solvent exposure is associated with neuropsychological impairment and whether such risk is modified by polymorphisms in the genes for enzymes involved in detoxification.
Design: Retrospective case-control analysis.
Methods: We studied 78 former dockyard painters and 42 community controls. Individual respiratory and dermal exposures to solvents were estimated. Neuropsychological tests were administered, including paper and pencil tests, tests from the Neurobehavioural Evaluation System (NES2), together with a structured neurological examination and genotyping of polymorphic enzymes involved in detoxification: GSTM1, GSTT1, GSTP1, NAT1, NAT2, SOD1 and CYP1A1.
Results: While initial case-control analyses failed to identify any significant differences between symptomatic and asymptomatic painters, in regression analyses increasing solvent exposure was associated with increasing risk of cognitive impairment, after adjustment for IQ (or age, where appropriate), smoking and alcohol. There was also an association between exposure and reduction in grip strength. There was limited evidence of risk modification by some enzyme polymorphisms.
Discussion: This association between increasing intensity of solvent exposure and neuropsychological impairment may be important at current exposure levels in the UK.

By using quantitative immunohistochemical and in situ hybridization techniques, we studied corticotropin‐releasing hormone (CRH) ‐producing neurons of the hypothalamic paraventricular nucleus (PVN) in patients who suffered from primary hypertension and died due to acute cardiac failure. The control group consisted of individuals who had normal blood pressure and died of acute heart failure due to mechanical trauma. Both magno‐ and parvocellular populations of CRH neurons appeared to be more numerous in the PVN of hypertensive patients. Quantitative analysis showed approximately a twofold increase in the total number of CRH neurons and a more than fivefold increase in the amount of CRH mRNA in the hypertensive PVN compared with the control. It is suggested that synthesis of CRH in hypertensive PVN is enhanced. Increased activity of CRH‐producing neurons in the PVN of hypertensive patients is proposed not only to entail hyperactivity of the hypothalamo‐pituitary‐adrenal axis, but also of the sympathetic nervous system and, thus, to be involved in the pathogenesis of hypertension. J. Comp. Neurol. 443:321–331, 2002. © 2002 Wiley‐Liss, Inc.

This article gives an overview of what multichannel surface electromyography can teach us about a motor unit. Background information is given about the generation of surface electromyography in general and surface motor unit potentials in particular. Furthermore, we describe how surface motor unit potentials are related to several motor unit characteristics, such as size, location, neuromuscular junction position, fiber length, fiber type, and metabolic fiber properties. In addition, we show how the spatial characteristics of multichannel surface electromyography can be used to obtain single‐surface motor unit potentials. The possibilities, challenges, and problems are discussed. Finally, several examples of surface motor unit potential analyses are given. © 2002 Wiley Periodicals, Inc. Muscle Nerve Supplement 11: S92–S97, 2002