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Background The modern wound dressing is produced to absorb fluid and protect against external contamination. The choice of which wound dressing to apply after surgery is usually based on local tradition. There are various impervious dressings on the market. Even if the wound is sterile before application, there will be subsequent recolonisation of skin microbiota. Previous studies suggest that a high bacterial load on the skin hampers wound healing and might be a risk for SSI.Aim The aim was to compare bacterial recolonisation on the shoulder under three different wound dressings, 48 h after sterile preparation of the skin as in preparation for surgery.Method In 25 healthy volunteers, a standard pre-surgical skin disinfection for a deltopectoral incision was made on the left shoulder with 0.5% chlorhexidine solution in 70% ethanol. Three different wound dressings were then placed on the shoulder, and 48 h later the skin beneath each dressing was swabbed, subsequently cultured and bacterial density analysed using viable count.Results The bacterial recolonisation under air-dry (gauze) dressing was significantly lower (p= .0001) compared to semipermeable and occlusive wound dressings.Conclusion Choosing a less permeable wound dressing may lead to an increased bacterial load on the skin during the first 48 h after surgery.

Rey, E, Kalén, A, Lorenzo-Martínez, M, López-Del Campo, R, Nevado-Garrosa, F, and Lago-Peñas, C. Elite soccer players do not cover less distance in the second half of the matches when game interruptions are considered. J Strength Cond Res38(4): 709–713, 2024—This study aimed to analyze quantitative differences in the physical demands of male elite soccer players between the first and second halves during official matches, accounting for effective playing time (the duration of play after subtracting the game interruptions) and playing positions. A total of 4,249 individual match observations of 412 outfield players competing in the Spanish first division league (LaLiga) were undertaken during the 2018–2019 season, using a computerized tracking system (TRACAB, Chyronhego, New York, NY). The players were classified into 5 positional roles: central defenders (CD), external defenders (ED), central midfielders (CM), external midfielders (EM), and forwards (F). The main results showed that in contrast to those observed when total playing time was considered, independent of playing position, there were no significant differences on high-speed running (HSR) (5.5 ± 2.4 vs. 5.5 ± 2.4 m·min−1) and sprint (5.3 ± 3.3 vs. 5.4 ± 3.3 m·min−1) distances between the first and second halves in professional soccer players when the effective playing time was considered. However, differences in match running performance at HSR and sprint distances between the first and second halves were dependent on players' playing position. Whereas ED and EM maintained HSR and sprint efforts during the second half, CD and CM significantly increased (p< 0.001) the distance covered at sprint during the second period of the match. Contrarily, F were unable to maintain their HSR (6.2 ± 2.3 vs. 5.9 ± 3.3 m·min−1) and sprint (7.0 ± 3.5 vs. 6.5 ± 3.4 m·min−1) match running performances during the second half. Such findings demonstrate that total playing time could overestimate fatigue-induced performance declines. Thus, effective playing time and playing position should be taken into account when interpreting the match running performance of professional soccer players.

ABSTRACTPurpose: The aim of this study was to examine the association between the time spent in possession by teams and the match-running performance in elite soccer matches.Methods: Match performance data were collected from players in Spanish LaLiga(8,468 individual match observations of 412 outfield players) using a multiple-camera computerised tracking system. A k-means cluster analyses classified teams depending on time spent in possession of the ball: very high-percentage ball possession teams (VHPBPT), high-percentage ball possession teams (HPBPT), low-percentage ball possession teams (LPBPT) and very low-percentage ball possession teams (VLPBPT).Results: Overall, physical indicators were highly associated with ball possession. Distances covered in VHPBPT were lower than HPBPT, LPBPT and VLPBPT, especially at low and medium speed. Position-specific changes were also evident for physical profiles. Attackers (central midfielders, external midfielders and forwards) in VHPBPT covered fewer meters per minute at any speed than their counterparts in HPBPT, LPBPT or VLPBPT. However, defenders (Central defenders and External defenders) in VLPBPT covered lower distances.Conclusion: These findings may have a great deal of practical implications and may help coaches to better understand match-running variations according to ball possession strategies and could be used to develop a model for predicting the physical activity profile in competition.

This study aimed to evaluate the test–retest reliability of soccer skill tests belonging to the F-MARC test battery. To avoid bias during talent identification and development, coaches and scouts should be using reliable tests for assessing soccer-specific skills in young male players. Fifty-two U-14 outfield male soccer players performed F-MARC soccer skill tests on two occasions, separated by 7 days. After familiarization, we administered two trial sessions of five skill tests: speed dribbling, juggling, shooting, passing, and heading. We assessed absolute reliability by expressing the standard error of measurement as a coefficient of variation with 95% limits of agreement, and we assessed relative reliability with the intraclass correlation coefficient and with Pearson’s correlation (r). The results demonstrated satisfactory relative and absolute reliability for speed dribbling, right foot juggling, short passing, shooting a dead ball right, shooting from a pass, heading in front, and heading right. However, reliability values for left foot juggling, chest-head-foot juggling, head-left-foot-right foot-chest-head juggling, long pass, and shooting a dead ball left tests were not strong enough to suggest their usage by coaches in training or sport scientists in research.

ABSTRACTThe aim of this study was to examine how the introduction of the VAR system influenced the play in elite soccer. The sample consists of 1024 matches played in the Italian Serie A and the German Bundesliga league during the seasons before and after the implementation of the VAR system. The following variables were recorded for each match: Fouls, Goals, Offsides, Penalties, Playing time in the first half, Playing time in the second half, Total Playing time, Red cards and Yellow cards. Match statistics were retrieved from the website of “Whoscored” (www.whoscored.com). A generalized linear model and a pairwise z-tests were used to compare seasons before and after the implementation of the VAR. There was a decrease in the number of offsides, fouls and yellow cards after the implementation of the VAR. Meanwhile, there was an increase in the number of minutes added to the playing time in the first half and the full game, but not in the second half. These findings may help coaches, players and managers to better understand the effects of the VAR system on professional soccer and to identify strategies to improve refereeing during matches.

AbstractThis study aimed to discover if the number of previous senior and youth national team championships played relates to the team and player performance at the European basketball championships. The sample consisted of all national teams and their players participating in the 2011, 2013 and 2015 European Championships for men (teams n = 72; players n = 697) and women (teams n = 52, players = 520). The teams were classified into four groups based on their highest stage reached in the tournament. A k-means cluster was used to group the players as high, medium or low performers according to their efficiency rating. The number of previous senior and youth championships was compared between groups. Better performing teams and players had a higher number of previous senior championships. The competitive experience differentiates low performing players for both genders, but only distinguishes high from medium performing players for women. No differences in the number of youth championships were found. It appears to be critical to have a sufficient amount of accumulated senior competitive experience within the team to reach the semi-final phase both for men’s and women’s national teams.

AbstractThis research explores the influence of playing with different recovery times between matches on physical activity and technical performance. The sample was composed by 4496 professional players who participated in German professional league (Deutsche Fußball Liga – DFL) during the season 2011–2012. Data were collected using a semi-automatic optical tracking system (VISTRACK, by Impire Corp., Germany). Differences on work rate profiles of soccer players were analysed for the following variables: total distance covered, number of fast runs, number of sprints and percentage of successful passes. The main finding of this study suggests that the total distance covered, the number of fast runs and the number of sprints decreased in professional soccer players in microcycles with length of <4 days during the mid-season. Central defenders, external defenders and external midfielders covered less total distance in microcycles of <4 days, and this effect was more evident during the mid-season. During three-day microcycles in comparison to four-day cycles, central defenders and external defenders reduced the total distance covered. No differences were observed between teams according to the team quality and match location. Coaches should pay extra attention to adapt recovery strategy according to playing position and period of season.

Background: Foam rolling has been extensively investigated, showing benefits in performance and recovery. Recently, vibration has been added to foam rollers, with hypothesized advantages over conventional foam rollers. However, there is no systematic evidence in this regard. Objective: To carry out a systematic review and meta-analysis about the effects of vibration foam roller (VFR) on performance and recovery. Methods: A systematic search was conducted in PubMed/MEDLINE, Web of Science and SportDiscus according to the PRISMA guidelines. The outcomes included performance (jump, agility and strength) and recovery variables (blood flow, pain and fatigue) measured after an intervention with VFR. The methodological quality was assessed with the PEDro scale. A random-effects model was used to perform the meta-analysis. Results: Initially, 556 studies were found and after the eligibility criteria 10 studies were included in the systematic review and 9 in the meta-analysis. There was no significant effects on jump performance (SMD = 0.14 [95% CI − 0.022 to 0.307]; p= 0.101; I2= 1.08%) and no significant beneficial effects were reported on isokinetic strength (SMD = 0.16 [95% CI − 0.041 to 0.367]; p= 0.117; I2= 9.7%). Recovery appears to be enhanced after VFR interventions, but agility does not seem to increase after VFR interventions. Conclusion: This systematic review and meta-analysis suggest that VFR could have great potential for increasing jump performance, agility, strength and enhancing recovery. Further research is needed to confirm the effects of VFR on performance and recovery.

All blood capillaries consist of endothelial tubes surrounded by mural cells referred to as pericytes. The origin, recruitment, and function of the pericytes is poorly understood, but the importance of these cells is underscored by the severe cardiovascular defects in mice genetically devoid of factors regulating pericyte recruitment to embryonic vessels, and by the association between pericyte loss and microangiopathy in diabetes mellitus. A general problem in the study of pericytes is the shortage of markers for these cells. To identify new markers for pericytes, we have taken advantage of the platelet-derived growth factor (PDGF)-B knockout mouse model, in which developing blood vessels in the central nervous system are almost completely devoid of pericytes. Using cDNA microarrays, we analyzed the gene expression in PDGF-B null embryos in comparison with corresponding wild-type embryos and searched for down-regulated genes. The most down-regulated gene present on our microarray was RGS5, a member of the RGS family of GTPase-activating proteins for G proteins. In situhybridization identified RGS5 expression in brain pericytes, and in pericytes and vascular smooth muscle cells in certain other, but not all, locations. Absence of RGS5 expression in PDGF-B and PDGFRβ-null embryos correlated with pericyte loss in these mice. Residual RGS5 expression in rare pericytes suggested that RGS5 is a pericyte marker expressed independently of PDGF-B/Rβ signaling. With RGS5 as a proof-of-principle, our data demonstrate the usefulness of microarray analysis of mouse models for abnormal pericyte development in the identification of new pericyte-specific markers.

Microarray hybridization has rapidly evolved as an important tool for genomic studies and studies of gene regulation at the transcriptome level. Expression profiles from homogenous samples such as yeast and mammalian cell cultures are currently extending our understanding of biology, whereas analyses of multicellular organisms are more difficult because of tissue complexity. The combination of laser microdissection, RNA amplification, and microarray hybridization has the potential to provide expression profiles from selected populations of cells in vivo. In this article, we present and evaluate an experimental procedure for global gene expression analysis of slender embryonic structures using laser microbeam microdissection and laser pressure catapulting. As a proof of principle, expression profiles from 1000 cells in the mouse embryonic (E9.5) dorsal aorta were generated and compared with profiles for captured mesenchymal cells located one cell diameter further away from the aortic lumen. A number of genes were overexpressed in the aorta, including 11 previously known markers for blood vessels. Among the blood vessel markers were endoglin, tie-2, PDGFB,and integrin-β1, that are important regulators of blood vessel formation. This demonstrates that microarray analysis of laser microbeam micro-dissected cells is sufficiently sensitive for identifying genes with regulative functions.

Transplants of fetal midbrain raphe neurons into the adult brain have been shown to promote recovery of complex behavioral deficits in several experimental models, but the mechanisms underlying these effects are only partially understood. In the present study, we have used a well-characterized model system to ascertain whether midbrain raphe graft can display behaviorally relevant changes in transmitter release and/or metabolism. Fetal mesencephalic raphe neurons were grafted unilaterally into the hippocampus previously deprived of its innate serotonergic innervation by intraventricular injections of 5,7-dihydroxytryptamine. The contralateral hippocampus remained as a nongrafted, lesioned control. Microdialysis probes were implanted in the hippocampus 5–7 months postgrafting. Under baseline conditions, extracellular levels of serotonin were similar to normal in the grafted hippocampi, but undetectable on the contralateral, nongrafted side. Levels of the serotonin metabolite, 5-hydroxyindoleacetic acid (5-HIAA), were markedly higher than normal in the grafted hippocampi, but dramatically reduced on the contralateral nongrafted side. Handling stimulation (gentle stroking of a rat's fur and tail for 15 min) induced a 64% increase in serotonin output in the intact rats and a small but significant 12% increase in the grafted animals. Nonnoxious tail-pinch (15 min) enhanced serotonin release by 86% in the intact rats and 28% in the grafted ones. Extracellular 5-HIAA levels remained unchanged during both handling and tail-pinch in both the intact and the grafted rats. Forced immobilization of the rats for 15 min induced a transient 124% increase in extracellular serotonin levels in the intact rats and a significant 19% increase in the grafted animals, whereas swimming in temperate water (25–30°C; 15 min) induced no detectable changes in serotonin output in any of the groups. 5-HIAA levels remained unchanged during forced immobilization, but were significantly reduced during the swimming session in both the intact (−38%) and grafted (−15%) animals. The present results indicate that median raphe grafts can become functionally integrated in the denervated host hippocampus and respond by altered indole output when the animal is exposed to different types of environmental challenges.

Development of a vascular system involves the assembly of two principal cell types - endothelial cells and vascular smooth muscle cells/pericytes (vSMC/PC) - into many different types of blood vessels. Most, if not all, vessels begin as endothelial tubes that subsequently acquire a vSMC/PC coating. We have previously shown that PDGF-B is critically involved in the recruitment of pericytes to brain capillaries and to the kidney glomerular capillary tuft. Here, we used desmin and alpha-smooth muscle actin (ASMA) as markers to analyze vSMC/PC development in PDGF-B-/- and PDGFR-beta-/- embryos. Both mutants showed a site-specific reduction of desmin-positive pericytes and ASMA-positive vSMC. We found that endothelial expression of PDGF-B was restricted to immature capillary endothelial cells and to the endothelium of growing arteries. BrdU labeling showed that PDGFR-beta-positive vSMC/PC progenitors normally proliferate at sites of endothelial PDGF-B expression. In PDGF-B-/- embryos, limb arterial vSMC showed a reduced BrdU-labeling index. This suggests a role of PDGF-B in vSMC/PC cell proliferation during vascular growth. Two modes of vSMC recruitment to newly formed vessels have previously been suggested: (1) de novo formation of vSMC by induction of undifferentiated perivascular mesenchymal cells, and (2) co-migration of vSMC from a preexisting pool of vSMC. Our data support both modes of vSMC/PC development and lead to a model in which PDGFR-beta-positive vSMC/PC progenitors initially form around certain vessels by PDGF-B-independent induction. Subsequent angiogenic sprouting and vessel enlargement involves PDGF-B-dependent vSMC/PC progenitor co-migration and proliferation, and/or PDGF-B-independent new induction of vSMC/PC, depending on tissue context.

Development of a vascular system involves the assembly of two principal cell types – endothelial cells and vascular smooth muscle cells/pericytes (vSMC/PC) – into many different types of blood vessels. Most, if not all, vessels begin as endothelial tubes that subsequently acquire a vSMC/PC coating. We have previously shown that PDGF-B is critically involved in the recruitment of pericytes to brain capillaries and to the kidney glomerular capillary tuft. Here, we used desmin and α-smooth muscle actin (ASMA) as markers to analyze vSMC/PC development in PDGF-B−/− and PDGFR-β−/− embryos. Both mutants showed a site-specific reduction of desmin-positive pericytes and ASMA-positive vSMC. We found that endothelial expression of PDGF-B was restricted to immature capillary endothelial cells and to the endothelium of growing arteries. BrdU labeling showed that PDGFR-β-positive vSMC/PC progenitors normally proliferate at sites of endothelial PDGF-B expression. In PDGF-B−/− embryos, limb arterial vSMC showed a reduced BrdU-labeling index. This suggests a role of PDGF-B in vSMC/PC cell proliferation during vascular growth. Two modes of vSMC recruitment to newly formed vessels have previously been suggested: (1) de novo formation of vSMC by induction of undifferentiated perivascular mesenchymal cells, and (2) co-migration of vSMC from a preexisting pool of vSMC. Our data support both modes of vSMC/PC development and lead to a model in which PDGFR-β-positive vSMC/PC progenitors initially form around certain vessels by PDGF-B-independent induction. Subsequent angiogenic sprouting and vessel enlargement involves PDGF-B-dependent vSMC/PC progenitor co-migration and proliferation, and/or PDGF-B-independent new induction of vSMC/PC, depending on tissue context.

Hippocampal extracellular levels of noradrenaline (NA) were monitored with the microdialysis technique during electrical stimulation of the lateral habenula (LHb) in halothane anaesthetized rats. The steady state NA level was 20.8±4.6 fmole/15 min of perfusion (mean ± SEM). Electrical stimulation of the LHb for 15 min (15 Hz, 0.5 mA) induced an immediate 228±48% increase in hippocampal NA release, compared to the pre-stimulation baseline (p<0.05). A second stimulation 90 min later induced a similar increase. The effect of LHb stimulation was completely abolished by a knife cut transecting the dorsal NA bundle either immediately rostral to the locus coeruleus or at the level of the parafascicular nucleus. This suggests that the effect was dependent on nerve impulses flow in the coeruleo-hippocampal NA neurons, and was not mediated, e.g., by a local spread of electricity into the hippocampus. Since the LHb has previously been shown to be a powerful activator of the mesencephalic raphe nuclei we tested whether the effect was mediated via the serotonergic system. However, the effect of LHb stimulation on hippocampal NA release persisted after 5,7-di-hydroxytryptamine treatment and after complete radiofrequency lesions of the dorsal and central superior raphe nuclei. The present data suggest that electrical stimulation of the LHb can increase hippocampal NA release through an activation of the locus coeruleus, and that this effect is not dependent on the mesencephalic raphe nuclei. The results support the role of the LHb as a link for limbic and striatal forebrain activation of brain stem monoaminergic systems.

The anatomical organization of projections from the medial septal nucleus (MS), and the vertical (VDB) and horizontal limb (HDB) of the diagonal band of Broca to the dorsal raphe nucleus (NRD) and the central superior raphe nucleus (RCS) of the rat were studied by anterograde [3H]-leucine, and True Blue and Fluoro Gold fluorescent retrograde tracing. Projections from the MS were found to enter the basal mesencephalon at the rostro-medial aspect of the pontine nuclei, curve dorsally and terminate throughout the RCS and in the caudal portion of the NRD. Fibers from the VDB were found to enter these raphe nuclei by two separate routes; some fibers reached the basal mesencephalon, curved dorsally and terminated in the RCS and NRD. Other fibers entered the pedunculopontine nucleus, curved medially and reached the NRD. Presumed terminal labelling was found overlaying the RCS and NRD throughout their rostro-caudal extensions. The brain stem projections from HDB entered the mesencephalon by the same routes as those from VDB, but the labelling over RCS was sparse, and the NRD labelling was preferentially distributed to the rostral portion of the nucleus. The present data indicate a crude topographic organization of the projections from the septal region to the NRD and RCS. In general, the distribution of presumed terminal labelling appeared to be more closely associated with the distribution of NRD and RCS 5-HT immunoreactive cell bodies, than with the cytoarchitectonically defined extensions of these raphe nuclei. By sequential evaluation of the distribution of retrogradely labelled and acetylcholine esterase-stained cells on the same section, and by selective tracing with radiolabelled choline, it appears that the vast majority, if not all, of the neurons in MS and diagonal band which project to the rostral raphe are non-cholinergic.

Gamma-aminobutyric acid (GABA)-releasing polymer matrices were implanted bilaterally, immediately dorsal to the substantia nigra, in rats previously kindled in the amygdala. Two days after implantation, rats with GABA-releasing matrices exhibited only focal limbic seizures in response to electrical stimulation, whereas animals with control matrices devoid of GABA had generalized convulsions. GABA release from the polymer matrices was high during the first days after implantation, as demonstrated both in vitro and, using microdialysis, in vivo. The anticonvulsant effect was no longer observed at 7 and 14 days at which time GABA release was found to be low. In a parallel experiment, polymer matrices containing noradrenaline (NA) were implanted bilaterally into the hippocampus of rats with extensive forebrain NA depletion induced by an intra-ventricular 6-hydroxydopamine injection. No effect on the development of hippocampal kindling was observed, despite extracellular NA levels exceeding those of rats with intrahippocampal locus coeruleus grafts that have previously been shown to retard kindling rate. The results indicate that GABA-releasing implants located in the substantia nigra region can suppress seizure generalization in epilepsy, even in the absence of synapse formation and integration with the host brain. In contrast, the failure of NA-releasing polymer matrices to retard the development of seizures in NA-depleted rats suggests that such an effect can only be exerted by grafts acting through a well-regulated, synaptic release of NA.

Patients with heterozygous familial hypercholesterolemia (n = 12) were treated either with pravastatin, a specific inhibitor of HMG-CoA reductase, or cholestyramine, followed by a period of combined treatment with both drugs. Initially, these patients had increased serum levels of low density lipoprotein (LDL) cholesterol (8.77 +/- 0.48 mmol/l; SEM), lathosterol (5.32 +/- 0.60 mg/l), and ubiquinone (0.76 +/- 0.09 mg/l), while the serum dolichol concentration was in the normal range. Cholestyramine treatment (n = 6) decreased the levels of LDL cholesterol (-32%) and increased lathosterol (+125%), but did not change dolichol or ubiquinone levels in a significant manner. Pravastatin treatment (n = 6) decreased LDL cholesterol (-27%), lathosterol (-46%), and ubiquinone (-29%). In this case, the amount of dolichol in serum also showed a small but statistically insignificant decrease (-16%) after 12 weeks of treatment. Combined treatment with cholestyramine and pravastatin (n = 6) resulted in changes that were similar to, but less pronounced than, those observed during pravastatin treatment alone. In no case was the ratio between ubiquinone and LDL cholesterol reduced. Possible effects on hepatic cholesterol, ubiquinone, and dolichol concentrations were studied in untreated (n = 2), cholestyramine-treated (n = 2), and pravastatin-treated (n = 4) gallstone patients and no consistent changes could be observed. The results indicate that treatment with pravastatin in familial hypercholesterolemia decreases serum ubiquinone levels in proportion to the reduction in LDL cholesterol.

The origins of the dopaminergic innervation of the rat dorsal raphe nucleus (NRD) have been investigated using a combination of fluorescent retrograde tracing and fluorescence histochemistry. Stereotaxic microinjections of True Blue were placed in the central, caudal and lateral portions of the NRD, and after 6–12 days survival the brains were processed for fluorescence histochemical detection of catecholamines. Retrogradely labeled neurons were searched for in the diencephalic A11 and A13 dopaminergic cell groups, substantia nigra, ventral tegmental area (VTA) and the linear, central superior and dorsal raphe nuclei. The various NRD injections consistently resulted in retrograde labeling of a small number of catecholamine-containing, presumed dopaminergic cell bodies, confined mainly to three regions: the VTA, the linear and central superior raphe nuclei and the NRD itself. The present findings indicate that not only dopaminergic neurons in the VTA but also the system of catecholamine-containing cells, extending dorsally and caudally from the VTA within the midline raphe area, project to the NRD. Although often similar in size, shape and distribution to the catecholaminergic neurons the majority of retrogradely labeled cells in these regions were, however, found to be non-catecholaminergic.

The activity of intrahippocampal transplants of cholinergic neurons was monitored by microdialysis in awake, freely moving rats. Fetal septal-diagonal band tissue was implanted into rats with a complete transection of the fimbria-fornix cholinergic pathway either as a cell suspension injected into the hippocampus or as a solid graft implanted in the lesion cavity. The grafts restored baseline acetylcholine release in the graft-reinnervated hippocampus to normal or supranormal levels. The graft-derived acetylcholine release was dependent on intact axonal impulse flow, and it was markedly increased during behavioral activation by sensory stimulation or by electrical stimulation of the lateral habenula. The results demonstrate that the septal grafts, despite their ectopic location, can become functionally integrated with the host brain and that the activity of the transplanted cholinergic neurons can be modulated from the host brain during ongoing behavior. Anatomical observations, using immunohistochemistry and retrograde tracing, indicate that direct or indirect brainstem afferents to the graft could mediate this functional integration. Host afferent control of the graft may thus play a role in the recovery of lesion-induced functional deficits seen with these types of transplants.

Solid grafts of autologous superior cervical ganglia (SCG) or fetal locus coeruleus (LC) were implanted unilaterally into a fimbria-fornix lesion cavity adjacent to the hippocampal formation after a 6-hydroxydopamine lesion of the intrinsic noradrenergic system. Twelve to 15 months after transplantation, one microdialysis probe was implanted in the dorsal hippocampus ipsilateral to the graft, and extracellular levels of noradrenaline (NA) were monitored during the application of pharmacological or behavioral stimuli. Age-matched intact and lesion-only animals served as controls. Morphological examination of the grafts was performed on sections processed for dopamine-β-hydroxylase (DBH) immunohistochemistry. In the lesion-only controls, the hippocampus was totally devoid of DBH-immunoreactive fibers and hippocampal levels of NA were generally undetectable. Although both SCG and LC grafts gave rise to an extensive DBH-immunoreactive fiber ingrowth in the ipsilateral hippocampus, baseline NA release was strikingly different in the two graft groups, being markedly lower than normal in the SCG-grafted rats (3.5 ± 0.1 fmol/30 μl) and significantly higher than normal in the LC-grafted rats (44.5 ± 12.3 fmol/30 μl). The response to potassium-induced depolarization (100 mMKCl in the perfusion fluid), neuronal uptake blockade (5 μMdesipramine), and sodium-channel blockade (1 μMTTX) was similar to normal in both graft groups. Exposure of the animals to mild (handling) or severe (immobilization) stressful stimuli significantly enhanced NA release in the intact controls, whereas no clear-cut effect could be detected in either graft group. Electrical stimulation of the medial septum, applied in an attempt to activate possible afferents to the grafts from the host septum, did not enhance NA release in any of the groups. The results show that grafts of both central and peripheral noradrenergic neurons can provide a source of steady-state NA release in the denervated hippocampus, but that the spontaneous activity of the grafted ganglionic neurons is very low compared to that of the LC neurons, probably due to the absence of a functional preganglionic input to the grafted SCG neurons. Although extracellular NA recovered from both the SCG- and the LC-grafted hippocampi is likely to derive from impulse-dependent neuronal release, it was largely unaffected by physiological stimuli applied to the host.

In 3002 patients with a femoral intracapsular neck fracture occurring during a 3-year period in the Stockholm area, 79 per cent were admitted from home and the remainder from different types of institutions. The mortality among these fracture patients was higher than in the general population. Patients admitted from institutions had a three to four times higher mortality rate than those coming from home. After 6 years, 54 per cent of the patients admitted from home were still alive compared with only 16 per cent of those admitted from institutions.

Kidney glomerulus mesangial cells fail to develop in mice carrying targeted null mutations in the platelet-derived growth factor (PDGF)-B or PDGF-Rbeta genes. We have examined the pattern of expression of these genes and smooth muscle markers during kidney development, to address the possible mechanisms underlying the mutant phenotypes. In wild-type embryos, PDGF-B was expressed in vascular endothelial cells, particularly in capillary endothelial cells in the developing glomeruli, whereas PDGF-Rbeta was found in perivascular mesenchymal cells in the developing renal cortex. In the course of glomerular development, small groups of PDGF-Rbeta and desmin-expressing cells collected in the 'S'-shaped and early cup-shaped vesicles, and at later stages such cells were found in the glomerular mesangium. In PDGF-B or -Rbeta null embryos, some PDGF-Rbeta/desmin or desmin-positive cells, respectively, were seen in early cup-shaped vesicles, but fewer than in the wild type, and further development of the mesangium failed. In mouse chimeras composed of PDGF-Rbeta +/+ and -/- cells, the Rbeta-/- cells failed to populate the glomerular mesangium. Our results show that while the mesangial cell lineage is specified independently of PDGF-B/Rbeta, these molecules provide critical permissive signals in mesangial cell development. We propose a model in which mesangial cells originate from PDGF-Rbeta-positive progenitors surrounding the developing glomerular afferent and efferent arterioles, and are co-recruited in response to PDGF-B during angiogenic formation of the glomerular capillary tuft.

Kidney glomerulus mesangial cells fail to develop in mice carrying targeted null mutations in the platelet-derived growth factor (PDGF)-B or PDGF-Rβ genes. We have examined the pattern of expression of these genes and smooth muscle markers during kidney development, to address the possible mechanisms underlying the mutant phenotypes. In wild-type embryos, PDGF-B was expressed in vascular endothelial cells, particularly in capillary endothelial cells in the developing glomeruli, whereas PDGF-Rβ was found in perivascular mesenchymal cells in the developing renal cortex. In the course of glomerular development, small groups of PDGF-Rβ and desmin-expressing cells collected in the ‘S’-shaped and early cup-shaped vesicles, and at later stages such cells were found in the glomerular mesangium. In PDGF-B or -Rβ null embryos, some PDGF-Rβ/desmin or desmin-positive cells, respectively, were seen in early cup-shaped vesicles, but fewer than in the wild type, and further development of the mesangium failed. In mouse chimeras composed of PDGF-Rβ +/+ and −/− cells, the Rβ−/− cells failed to populate the glomerular mesangium. Our results show that while the mesangial cell lineage is specified independently of PDGF-B/Rβ, these molecules provide critical permissive signals in mesangial cell development. We propose a model in which mesangial cells originate from PDGF-Rβ-positive progenitors surrounding the developing glomerular afferent and efferent arterioles, and are co-recruited in response to PDGF-B during angiogenic formation of the glomerular capillary tuft.

The importance of perivascular–endothelial cell interactions during blood vessel development is discussed in the light of recent findings in plateletderived growth factorB, plateletderived growth factor receptorβ, angiopoietin1 and tie2 knockout mice, which all show deficient development of perivascular cells. The initial formation of networks of endothelial tubes (vasculogenesis) does not seem to depend on the perivascular cells but subsequent vessel remodeling relies on mesenchymal–endothelial shortrange signaling. Based on findings in plateletderived growth factor and plateletderived growth factor receptor knockout mice, a general model for the role of plateletderived growth factors in smooth muscle development is proposed. Curr Opin Lipidol 9:407–411. © 1998 Lippincott Williams & Wilkins

The semi-invasive technique for electrical stimulation of bone healing developed by Brighton et al. (1977) was used in 23 patients with nonunited fractures of the tibia (14 cases), humerus (4 cases), scaphoid, femur and fibula as well as one failed arthrodesis of the ankle. The fractures were clinically not healed and not operated on within a minimum of 6 months. The mean period from fracture to treatment was 18 months. Electrical stimulation led to solid bone healing in 10 cases. Two deep infections occurred during the treatment. Of 13 cases that did not unite, a great range of motion in the nonunion area was an obvious cause of failure in seven cases. The results in this series cannot compete with those of bone graft surgery for nonunions.

Large additions of O2 during the pretreatment of modified or industrial kraft pulp with NO2 under conditions which favored an autocatalytic generation of NO2 from produced and added HNO3 led to a decreased viscosity after a subsequent oxygen bleaching, If the comparison was made at high kappa numbers. The difference was less apparent when the oxygen bleaching was extended. The yield of pulp at a given kappa number was reduced by large O2 additions. An Increased yield of nitric acid contributed to these effects.Hydrogen cyanide and ammonia were produced during the pretreatment in reactions between lignin and generated nitrogen oxides. Addition of O2 led to decreased yields of these products.

In a randomized double-blind study involving 42 postmenopausal women with a displaced Colles' fracture, we investigated whether piroxicam, a nonsteroid anti-inflammatory drug, can reduce posttraumatic osteopenia and improve the rate of recovery. In an earlier study [3] we found a bone-sparing effect caused by piroxicam after external fixation of the rabbit hindleg. The patients were treated with a below-elbow paster slab for 4 weeks after the reduction. The bone mineral content of the forearm bones was measured with a single-photon absorptiometer 8 weeks after the fracture. There was a mean 7% bone mineral decrease in the radius and 5% in the ulna among the patients treated with piroxicam versus 10% in the radius and 7% in the ulna in the placebo group. However, this difference was not significant. Piroxicam did not decrease the rate of fracture healing. The patients who received piroxicam had significantly less pain during plaster treatment, but there was no difference in the rate of functional recovery between the groups.

Gamma-aminobutyric acid (GABA)-releasing polymer matrices were implanted bilaterally, immediately dorsal to the substantia nigra, in rats previously kindled in the amygdala. Two days after implantation, rats with GABA-releasing matrices exhibited only focal limbic seizures in response to electrical stimulation, whereas animals with control matrices devoid of GABA had generalized convulsions. GABA release from the polymer matrices was high during the first days after implantation, as demonstrated both in vitro and, using microdialysis, in vivo. The anticonvulsant effect was no longer observed at 7 and 14 days at which time GABA release was found to be low. In a parallel experiment, polymer matrices containing noradrenaline (NA) were implanted bilaterally into the hippocampus of rats with extensive forebrain NA depletion induced by an intraventricular 6-hydroxydopamine injection. No effect on the development of hippocampal kindling was observed, despite extracellular NA levels exceeding those of rats with intrahippocampal locus coeruleus grafts that have previously been shown to retard kindling rate. The results indicate that GABA-releasing implants located in the substantia nigra region can suppress seizure generalization in epilepsy, even in the absence of synapse formation and integration with the host brain. In contrast, the failure of NA-releasing polymer matrices to retard the development of seizures in NA-depleted rats suggests that such an effect can only be exerted by grafts acting through a well-regulated, synaptic release of NA.

Summary Inhibitors of hydroxymethylglutaryl coenzyme A reductase are used clinically to decrease blood levels of low-density lipoprotein cholesterol in hypercholesterolemic patients. However, little is known about the possible effects of these inhibitors on dolichol and cholesterol synthesis. Oral administration of mevinolin to rats was found here to decrease dolichol, dolichyl-P and coenzyme Q levels in the heart and skeletal muscle and to increase the hepatic dolichol level while decreasing the coenzyme Q content in this same organ. The amounts of dolichyl-P decreased in heart and muscle and increased in brain. Intraperitoneal administration also affected the levels of these lipids. The concentrations of blood lipids were not modified in the same manner as tissue lipids. Analysis of individual enzyme activities and of incorporation of [3H]acetate into various lipids of liver and brain slices demonstrated that both up- and down-regulation of different proteins occur in various tissues, resulting in modifications in lipid synthesis. Hypercholesterolemic patients were found to have high blood coenzyme Q levels, which are decreased upon pravastatin treatment, although they are still above control values. It appears that these HMG-coenzyme A reductase inhibitors do not selectively lower cholesterol levels, but that they also modify the dolichol and coenzyme Q content and synthesis both in the liver and various other tissues.

The aim of this study was to investigate the predisposing factors, fracture location, treatment, and final outcome of femoral fractures after total hip arthroplasty (THA). From 1975 to 1983, 28 patients were seen with 29 fractures on the same side as the prosthesis. Most of the fractures were caused by minor trauma, and prior hip surgery was the most common predisposing factor. Two patients underwent early operation and six were treated with protected weight bearing. Twenty-one underwent initial skeletal traction, and 14 of these fractures united without further surgery. Six of the patients treated with initial skeletal traction were operated on early, mainly by osteosynthesis, due to poor fracture alignment. Three of these fractures united, but one subsequently required revision arthroplasty because of loosening of the femoral component. Two patients died and three had a permanent pseudarthrosis or a Girdlestone resection. Nineteen of the 21 fractures not operated on united and five of the eight operated united. The results indicate that when good fracture alignment is achieved with traction, union is not jeopardized by either the prosthesis or the cement.

A consecutive series of 64 halo-vest-treated unstable cervical spine injuries is described. We agree with earlier investigators on the advantages of halo-vest treatment. For several types of injuries affecting the cervical spine we prefer the halo-vest method, which has a low rate of technical failures and complications. The healing rate was found to be high. Hospitalization was very short with the halo-vest method.

The changing supply of warm Circumpolar Deep Water (CDW) to the West Antarctic continental shelf is responsible for the basal melting and thinning of the West Antarctic ice shelves that has occurred in recent decades. Here we assess the variability in CDW supply, and its drivers, from a multiyear mooring deployed in, and a regional ocean model spanning, the Getz‐Dotson Trough, Amundsen Sea. Between 2010 to 2015, the CDW within the trough underwent a pronounced cooling and freshening, associated with changes in thermohaline properties on isopycnals. Variability in the rate of CDW inflow is controlled by local wind forcing of a shelf break undercurrent, which determines the hydrographic properties of inflowing CDW via tilting of density surfaces above the continental slope. Local wind is coupled to the Amundsen Sea Low (ASL) low‐pressure system, which is modulated by large‐scale climatic modes via atmospheric teleconnections. For the period analyzed, a deeper ASL was associated with westward wind anomaly at the shelf break. Changes in the sea surface slope decelerated the shelf break undercurrent, resulting in less heat accessing the continental shelf and, consequently, a cooling of the Getz‐Dotson Trough. Therefore, the present work suggests that the fate of the West Antarctic ice shelves is closely tied to the future evolution of the ASL. The heat available for the melting of the ice shelves of the Amundsen Sea is supplied by the warm waters flooding the continental shelf. Here we show that the waters flowing into the Getz‐Dotson Trough underwent a pronounced cooling between 2010 and 2015, associated with a weakening of the bottom‐intensified currents within the trough. This process was controlled by changes of shelf break winds. A weakening of the eastward wind impacts the middepth undercurrent system above the continental slope, which controls the inflow of warm water via tilting of density surfaces above the slope. The local winds are modulated by the low‐pressure system located offshore of the Amundsen Sea, known as the Amundsen Sea Low. The Amundsen Sea circulation is controlled by this low‐pressure system, and changes in its configuration can impact the warmer waters flooding the West Antarctic continental shelf, with consequences for the melting of the region's ice shelves. Circumpolar Deep Water inflow to the Getz‐Dotson Trough, Amundsen Sea, is investigated with a multiyear mooringOn‐shelf heat content decreased between 2010 and 2015 in response to weaker Circumpolar Deep Water inflowGetz‐Dotson Trough cooling is driven by a westward wind anomaly at the shelf break, associated with a deeper Amundsen Sea Low

The bone mineral content of the radius and ulna was analyzed in 31 postmenopausal women with displaced Colles' fractures. Sixteen fractures were treated with a below-the-elbow plaster cast and 15 with primary external fixation. The bone mineral content of the forearm bones was measured with a photon absorptiometer 9 (6-24) months later. There was a mean 15 percent mineral decrease in the radius, but no difference between the two treatment groups. The decrease did not correlate with the age of the patient, nor was there any correlation with grip strength or range of wrist motion. The more severe fractures, according to the Frykman classification, had a more pronounced mineral loss than the simpler fractures.