In-Depth Characterization of Layer 5 Output Neurons of the Primary Somatosensory Cortex Innervating the Mouse Dorsal Spinal Cord.

Neuronal circuits of the spinal dorsal horn integrate sensory information from the periphery with inhibitory and facilitating input from higher central nervous system areas. Most previous work focused on projections descending from the hindbrain. Less is known about inputs descending from the cerebral cortex. Here, we identified cholecystokinin (CCK) positive layer 5 pyramidal neurons of the primary somatosensory cortex (CCK + S1-corticospinal tract [CST] neurons) as a major source of input to the spinal dorsal horn. We combined intersectional genetics and virus-mediated gene transfer to characterize CCK+ S1-CST neurons and to define their presynaptic input and postsynaptic target neurons. We found that S1-CST neurons constitute a heterogeneous population that can be subdivided into distinct molecular subgroups. Rabies-based retrograde tracing revealed monosynaptic input from layer 2/3 pyramidal neurons, from parvalbumin positive cortical interneurons, and from thalamic relay neurons in the ventral posterolateral nucleus. Wheat germ agglutinin-based anterograde tracing identified postsynaptic target neurons in dorsal horn laminae III and IV. About 60% of these neurons were inhibitory and about 60% of all spinal target neurons expressed the transcription factor c-Maf. The heterogeneous nature of both S1-CST neurons and their spinal targets suggest complex roles in the fine-tuning of sensory processing.

Exercise training increases skeletal muscle mitochondrial volume density by enlargement of existing mitochondria and not de novo biogenesis.

AIMS: (i) To determine whether exercise-induced increases in muscle mitochondrial volume density (MitoVD ) are related to enlargement of existing mitochondria or de novo biogenesis and (ii) to establish whether measures of mitochondrial-specific enzymatic activities are valid biomarkers for exercise-induced increases in MitoVD . METHOD: Skeletal muscle samples were collected from 21 healthy males prior to and following 6 weeks of endurance training. Transmission electron microscopy was used for the estimation of mitochondrial densities and profiles. Biochemical assays, western blotting and high-resolution respirometry were applied to detect changes in specific mitochondrial functions. RESULT: MitoVD increased with 55 ± 9% (P < 0.001), whereas the number of mitochondrial profiles per area of skeletal muscle remained unchanged following training. Citrate synthase activity (CS) increased (44 ± 12%, P < 0.001); however, there were no functional changes in oxidative phosphorylation capacity (OXPHOS, CI+IIP ) or cytochrome c oxidase (COX) activity. Correlations were found between MitoVD and CS (P = 0.01; r = 0.58), OXPHOS, CI+CIIP (P = 0.01; R = 0.58) and COX (P = 0.02; R = 0.52) before training; after training, a correlation was found between MitoVD and CS activity only (P = 0.04; R = 0.49). Intrinsic respiratory capacities decreased (P < 0.05) with training when respiration was normalized to MitoVD. This was not the case when normalized to CS activity although the percentage change was comparable. CONCLUSIONS: MitoVD was increased by inducing mitochondrial enlargement rather than de novo biogenesis. CS activity may be appropriate to track training-induced changes in MitoVD.

Evidence for enzootic circulation of Rift Valley fever virus among livestock in Cameroon.

Rift Valley fever virus (RVFV) is an arthropod-borne pathogen, causing serious epidemics in Africa and the Arabian Peninsula. In Cameroon serological data indicate the presence of RVFV, but active circulation of RVFV, causing clinical infections has not been proven yet. For this purpose we carried out a serological and molecular study on a total of 1953 randomly selected serum samples of small ruminants and cattle, which were collected in years 2013 and 2014 in Cameroon. In a first step, sera were screened serologically using a variety of assay formats to reveal RVFV specific antibodies. At the second stage, seropositive specimen were assessed for acute RVFV infections via IgM-specific ELISA and quantitative real-time RT-PCR. Our data show a significant difference in the antibody prevalence in cattle (13.5% [95% confidence interval: 11.4-15.7]) and small ruminants (3.4% [95% confidence interval: 2.3-4.7]), with indications for annual fluctuations and significant regional differences of seropositivity. One small ruminant and three bovines were eventually found to be positive in IgM ELISA and indications for viremia were found in one bovine by RVFV genome detection using quantitative real-time RT-PCR. The results of this study therefore corroborate the presence of acute RVFV-infection and its circulation in Cameroon.

Rift Valley fever virus infections in Egyptian cattle and their prevention.

Rift Valley fever virus (RVFV) causes consistently severe outbreaks with high public health impacts and economic losses in livestock in many African countries and has also been introduced to Saudi Arabia and Yemen. Egypt with its four large outbreaks in the last 40 years represents the northernmost endemic area of RVFV. The purpose of this study was to provide an insight into the current anti-RVFV antibody status in immunized as well as non-immunized dairy cattle from the Nile Delta of Egypt. During 2013-2015, a total of 4,167 dairy cattle from four governorates including Dakahlia, Damietta, Gharbia and Port Said were investigated. All cattle were born after 2007 and therewith after the last reported Egyptian RVFV outbreak in 2003. The samples derived from vaccinated animals from 26 different dairy farms as well as non-immunized cattle from 27 different smallholding flocks. All samples were examined following a three-part analysis including a commercially available competition ELISA, an in-house immunofluorescence assay and a virus neutralization test. Additionally, a subset of samples was analysed for acute infections using IgM ELISA and real-time reverse transcriptase PCR. The results indicated that the RVFV is still circulating in Egypt as about 10% of the non-immunized animals exhibited RVFV-specific antibodies. Surprisingly, the antibody prevalence in immunized animals was not significantly higher than that in non-vaccinated animals which points out the need for further evaluation of the vaccination programme. Due to the substantial role of livestock in the amplification and transmission of RVFV, further recurrent monitoring of the antibody prevalence in susceptible species is highly warranted.

Serological and genomic evidence of Rift Valley fever virus during inter-epidemic periods in Mauritania.

Rift Valley fever virus (RVFV) is an emerging pathogen of major concern throughout Africa and the Arabian Peninsula, affecting both livestock and humans. In the past recurrent epidemics were reported in Mauritania and studies focused on the analysis of samples from affected populations during acute outbreaks. To verify characteristics and presence of RVFV during non-epidemic periods we implemented a multi-stage serological and molecular analysis. Serum samples of small ruminants, cattle and camels were obtained from Mauritania during an inter-epidemic period in 2012-2013. This paper presents a comparative analysis of potential variations and shifts of antibody presence and the capability of inter-epidemic infections in Mauritanian livestock. We observed distinct serological differences between tested species (seroprevalence: small ruminants 3·8%, cattle 15·4%, camels 32·0%). In one single bovine from Nouakchott, a recent RVF infection could be identified by the simultaneous detection of IgM antibodies and viral RNA. This study indicates the occurrence of a low-level enzootic RVFV circulation in livestock in Mauritania. Moreover, results indicate that small ruminants can preferably act as sentinels for RVF surveillance.

Long wavelength multiphoton excitation is advantageous for intravital kidney imaging.

Intravital multiphoton microscopy is a powerful tool to study kidney physiology in living animals. However, certain technical issues have curbed its usage to date, including limited depth of tissue penetration and high background emission of endogenous signals. Most previous studies have used the excitation range 700­1000 nm. Since newer longer wavelength excitation lasers may provide solutions to these problems we constructed a microscope coupled to a laser tunable up to 1300 nm and optimized for kidney imaging. This set-up offers substantial advantages for intravital studies, especially when coupled with newly available far-red probes. First, the background at longer wavelengths is markedly reduced, thus increasing the signal to background ratio. Second, the depth of tissue penetration is significantly increased, enabling detailed imaging of previously inaccessible structures, such as deeper glomeruli. Third, using a combination of two- and three-photon excitation, multiple different fluorescent probes can be imaged simultaneously in the same animal, with clear spectral separation. Application of these techniques helped visualize pathological aspects of tubular cell function in a well-established model of acute kidney injury (maleate toxicity). Thus, utilizing long wavelength excitation offers substantial advantages for intravital kidney imaging, which together enhance the capabilities of this powerful and increasingly used research technique.

Integrin inhibition promotes atypical anoikis in glioma cells.

Integrins regulate cellular adhesion and transmit signals important for cell survival, proliferation and motility. They are expressed by glioma cells and may contribute to their malignant phenotype. Integrin inhibition may therefore represent a promising therapeutic strategy. GL-261 and SMA-560 glioma cells grown under standard conditions uniformly detached and formed large cell clusters after integrin gene silencing or pharmacological inhibition using EMD-121974, a synthetic Arg-Gly-Asp-motif peptide, or GLPG0187, a nonpeptidic integrin inhibitor. After 120 h, the clusters induced by integrin inhibition decayed and cells died. In contrast, when cells were cultured under stem cell (sphere) conditions, no disaggregation became apparent upon integrin inhibition, and cell death was not observed. As poly-HEMA-mediated detachment had similar effects on cell viability as integrin inhibition, we postulated that cell death may result from detachment alone, which was confirmed using various permissive and nonpermissive substrates. No surrogate markers of apoptosis were detected and electron microscopy confirmed that necrosis represents the dominant morphology of detachment-induced cell death. In addition, integrin inhibition resulted in the induction of autophagy that represents a survival signal. When integrins were inhibited in nonsphere glioma cells, the TGF-ß pathway was strongly impaired, whereas no such effect was observed in glioma cells cultured under sphere conditions. Cell death induced by integrin inhibition was rescued by the addition of recombinant transforming growth factor-ß (TGF-ß) and accelerated by exposure to the TGF-ß receptor inhibitor, SD-208. In summary, cell death following integrin inhibition is detachment mediated, represents an atypical form of anoikis involving necrosis as well as autophagy, and is modulated by TGF-ß pathway activity.

Indigenous West Nile virus infections in horses in Albania.

Serum samples collected from 167 equines of 12 districts in Albania were tested for West Nile virus-specific antibodies by enzyme-linked immunosorbent assay and virus neutralization assay, using WNV lineage 1 and 2. In addition, 95 bird serum samples from Albania and 29 horse samples from Kosovo were tested in ELISA. An overall seroprevalence rate of 22% was found in horses from Albania, whereas no specific antibodies were found in the equine samples from Kosovo and the bird samples. This is the first report indicating WNV infections in animals in Albania, and the first reported seroprevalence study conducted for Kosovo. These results provide evidence for widespread infections of WNV in Albania.

Monitoring of West Nile virus infections in Germany.

West Nile virus (WNV) is a flavivirus that is maintained in an enzootic cycle between ornithophilic mosquitoes, mainly of the Culex genus, and certain wild bird species. Other bird species like ravens, jays and raptors are highly susceptible to the infection and may develop deadly encephalitis, while further species of birds are only going through subclinical infection. The objective of this study was to continue in years 2009-2011 the serological and molecular surveillance in wild birds in Germany (see Vector Borne Zoonotic Dis. 10, 639) and to expand these investigations for the first time also to sera from domestic poultry and horses collected between 2005 and 2009. All three cohorts function as indicators for the endemic circulation of WNV. The presence of WNV-specific antibodies was detected in all samples by virus neutralization test (VNT), indirect immunofluorescence test (IFT) and/or enzyme-linked immunosorbent assay (ELISA). The presence of WNV genomes was monitored in relevant sera using two qRT-PCRs that amplify lineage 1 and 2 strains. A total of 364 migratory and resident wild bird serum samples (with emphasis on Passeriformes and Falconiformes) as well as 1119 serum samples from domestic poultry and 1282 sera from horses were analysed. With the exception of one hooded crow, antibody carriers were exclusively found in migratory birds, but not in resident birds/domestic poultry or in local horses. Crows are facultative, short-distance winter migrants in Germany. WNV-specific nucleic acids could not be demonstrated in any of the samples. According to these data, there is no convincing evidence for indigenous WNV infections in equines and in wild/domestic birds in Germany. However, since a few years, WNV infections are endemic in other European countries such as Austria, Hungary, Greece and Italy, a state-of-the-art surveillance system for the detection of incursions of WNV into Germany deems mandatory.

Pathogenesis of classical and atypical BSE in cattle.

It is known from earlier studies that the pathogenesis of BSE in cattle differs considerably from the TSE pathogenesis in sheep, where the lymphoreticular system (LRS) is majorly involved in the transport and propagation of the agent. In cattle, the BSE agent has only been detected in the Peyer's patches of the distal ileum and in the tonsils, which have both been identified as the portal of entry for the agent after oral uptake. It was shown that as opposed to most other animal species, in cattle the BSE agent amplifies almost exclusively in the central and peripheral nervous system. However, there is growing evidence for a centrifugal spread from the central nervous system into the periphery at the late stage of the disease. Moreover, there are only very limited data available concerning the pathogenesis of both atypical BSE forms, H type and L type BSE, as compared to classical BSE. In this manuscript we summarize the most recent data that we generated on the classical BSE pathogenesis after an oral challenge study that was performed with 56 cattle. Preliminary results on the pathogenesis of both atypical BSE forms are also presented, based on an intracranial challenge of cattle with German isolates of both atypical BSE forms.

Experimental challenge of cattle with German atypical bovine spongiform encephalopathy (BSE) isolates.

For almost two decades after the discovery of the first bovine spongiform encephalopathy (BSE) case, it was generally accepted that only one BSE strain existed globally. However, in 2004, two novel BSE forms (L-type and H-type) were separately identified in two different European Member States, forms that differed from the classical (C-type) form by their biochemical properties and by the pattern of PrP(Sc) deposition as determined by immunohistochemistry (IHC). 60 atypical BSE cases have been identified worldwide as of November 2010, including one H- and one L-type BSE case each in Germany. However, it was not known whether the biological properties (pathogenesis and agent distribution, as well as transmissibility to other species) of these novel forms were the same as in classical BSE cases. Eleven calves were thus challenged intracranially, five with the German H-type and six with German L-type BSE cases. The experimental design and the clinical studies, followed by laboratory testing, are described in this manuscript.

[Prevalence and incidence of dementia in Germany--a study based on data from the public sick funds in 2002]. / Prävalenz und Inzidenz von Demenz in Deutschland--Eine Studie auf Basis von Daten der gesetzlichen Krankenversicherungen von 2002.

So far all calculations of the number of demented people are based on rates from meta-analyses, mean rates of meta-analyses or spatial analyses. This article presents age- and gender-specific prevalence and incidence rates of dementia that are based on a large sample of the German Sick Funds (Stichprobendaten von Versicherten der gesetzlichen Krankenversicherung (GKV)) with 2.3 million people from the year 2002. Prevalence rates increase from 0.8% and 0.6% for 60-64 year old men and women to 30% and 43% for men and women aged 100 or older, respectively. Incidence rates increase from 0.18 and 0.14 cases per 100 person-years for 60-64-year old men and women to 9.9 and 10.9 for over 95 year old men and women, respectively. Our results confirm rates from earlier studies on the basis of meta-analyses. Regional differences show for the first time that higher prevalence rates exist for East German women and men above age 85. In 2007 about 1.07 million moderately or severely demented people live in Germany of which about 244 000 are incident cases when we extrapolate our rates to the population of this year.

Mycoplasma suis invades porcine erythrocytes.

Mycoplasma suis belongs to the hemotrophic mycoplasma group and causes infectious anemia in pigs. According to the present state of knowledge, this organism adheres to the surface of erythrocytes but does not invade them. We found a novel M. suis isolate that caused severe anemia in pigs with a fatal disease course. Interestingly, only marginal numbers of the bacteria were visible on and between the erythrocytes in acridine orange-stained blood smears for acutely diseased pigs, whereas very high loads of M. suis were detected in the same blood samples by quantitative PCR. These findings indicated that M. suis is capable of invading erythrocytes. By use of fluorescent labeling of M. suis and examination by confocal laser scanning microscopy, as well as scanning and transmission electron microscopy, we proved that the localization of M. suis was intracellular. This organism invades erythrocytes in an endocytosis-like process and is initially surrounded by two membranes, and it was also found floating freely in the cytoplasm. In conclusion, we were able to prove for the first time that a member of the hemotrophic mycoplasma group is able to invade the erythrocytes of its host. Such colonization should protect the bacterial cells from the host's immune response and hamper antibiotic treatment. In addition, an intracellular life cycle may explain the chronic nature of hemotrophic mycoplasma infections and should serve as the foundation for novel strategies in hemotrophic mycoplasma research (e.g., treatment or prophylaxis).

Characterization of a 320-kb region containing the HEXA gene on bovine chromosome 10 and analysis of its association with BSE susceptibility.

Bovine spongiform encephalopathy (BSE) belongs to a group of neurodegenerative diseases known as transmissible prion diseases. Recently, variants in the promoter region of the prion protein (PRNP) gene have been shown to have a considerable effect on the susceptibility to BSE. However, a previous genome scan revealed other putative BSE-susceptibility loci. Here, we analysed such a region on BTA10, which contains the functional candidate gene HEXA. Three hundred and twenty kilobases that, besides HEXA, also contain ARIH1, BRUNOL6 and PARP6 were characterized and screened for polymorphisms. Genotyping of 38 SNPs in Holstein-Friesian animals from the UK (350 diseased and 270 controls) revealed two intronic SNPs that were associated with BSE incidence, with experiment-wise P-values of 3.5 x 10(-3) and 7.7 x 10(-3) respectively. Both SNPs were in strong linkage disequilibrium and the rare alleles had a protective effect. These alleles were contained in a haplotype dubbed 'UK-protective' that was significantly overrepresented in the controls with a permuted P-value of 2 x 10(-3). An association study in German Holstein animals (73 diseased and 627 controls) revealed an opposite effect of the 'UK-protective' haplotype in this population, i.e. it was overrepresented in the diseased animals, although not significant after correction for multiple testing. These findings indicate a causal variant for BSE susceptibility on BTA10 in linkage disequilibrium with the markers studied. Candidate gene analyses of the surrounding region and additional association studies will help to clarify the origin of the protective effects and to identify causal variants for BSE susceptibility on BTA10.

Ifosfamide metabolites CAA, 4-OH-Ifo and Ifo-mustard reduce apical phosphate transport by changing NaPi-IIa in OK cells.

Renal Fanconi syndrome occurs in about 1-5% of all children treated with Ifosfamide (Ifo) and impairment of renal phosphate reabsorption in about 20-30% of them. Pathophysiological mechanisms of Ifo-induced nephropathy are ill defined. The aim has been to investigate whether Ifo metabolites affect the type IIa sodium-dependent phosphate transporter (NaPi-IIa) in viable opossum kidney cells. Ifo did not influence viability of cells or NaPi-IIa-mediated transport up to 1 mM/24 h. Incubation of confluent cells with chloroacetaldehyde (CAA) and 4-hydroperoxyIfosfamide (4-OH-Ifo) led to cell death by necrosis in a concentration-dependent manner. At low concentrations (50-100 microM/24 h), cell viability was normal but apical phosphate transport, NaPi-IIa protein, and -mRNA expression were significantly reduced. Coincubation with sodium-2-mercaptoethanesulfonate (MESNA) prevented the inhibitory action of CAA but not of 4-OH-Ifo; DiMESNA had no effect. Incubation with Ifosfamide-mustard (Ifo-mustard) did alter cell viability at concentrations above 500 microM/24 h. At lower concentrations (50-100 microM/24 h), it led to significant reduction in phosphate transport, NaPi-IIa protein, and mRNA expression. MESNA did not block these effects. The effect of Ifo-mustard was due to internalization of NaPi-IIa. Cyclophosphamide-mustard (CyP-mustard) did not have any influence on cell survival up to 1000 microM, but the inhibitory effect on phosphate transport and on NaPi-IIa protein was the same as found after Ifo-mustard. In conclusion, CAA, 4-OH-Ifo, and Ifo- and CyP-mustard are able to inhibit sodium-dependent phosphate cotransport in viable opossum kidney cells. The Ifo-mustard effect took place via internalization and reduction of de novo synthesis of NaPi-IIa. Therefore, it is possible that Ifo-mustard plays an important role in pathogenesis of Ifo-induced nephropathy.

Impact of carbon dioxide versus air pneumoperitoneum on peritoneal cell migration and cell fate.

BACKGROUND: Postoperative systemic immune function is suppressed after open abdominal surgery, as compared with that after minimally invasive abdominal surgery. As a first line of defense, peritoneal macrophages (PMo) and polymorphonuclear neutrophil granulocytes (PMNs) are of primary importance in protecting the body from microorganisms. Previous studies have shown changes in these cell populations over time after open versus laparoscopic surgery. This study aimed to investigate the dynamics of cell recruitment and clearance of peritoneal cells. METHODS: Female NMRI mice (33 +/- 2 g) were randomly assigned to carbon dioxide (CO2) or air insufflation. Intravasal cells with phagocytic capabilities were selectively stained by intravenous injection of the fluorescent dye PKH26 24 h before surgery. Gas was insufflated into the peritoneal cavity through a catheter, and the pneumoperitoneum was maintained for 30 min. Peritoneal lavage was performed 1, 3, 8, or 24 h after surgery. Apoptotic cells were assessed by flow cytometry using a general caspase substrate. RESULTS: The total peritoneal cell count did not differ between groups. The PKH26-positive PMo level was significantly increased after CO2, as compared with air, at 1 h and 24 h. The ratio of apoptotic PMo did not differ between the groups. In the peritoneal lavage, polymorphonuclear leukocytes (PMNs) were tripled in the air group, as compared with the CO2 group, whereas the ratio of apoptotic PMNs was significantly decreased. There was a higher fraction of PKH26-positive PMNs after air exposure, as compared with that after CO2. CONCLUSIONS: Air exposure triggered a higher transmigration rate of PMNs from the blood compartment into the peritoneal cavity and decreased PMN apoptosis, as compared with CO2. The lower proportion of PKH26-positive peritoneal macrophages in the air group might have been attributable to a higher inflammatory stimulation than in the CO2 group, leading to increased emigration of PMo to draining lymph nodes. All the findings underscore a complex cell-specific regulation of cell recruitment and clearance in the peritoneal compartment.

Expression of smoothelin in the normal and the overactive human bladder.

PURPOSE: We established the expression pattern of smoothelin, a marker protein for contractile smooth muscle cells, in the human detrusor and investigated its possible impact on bladder overactivity. MATERIALS AND METHODS: Detrusor samples of 13 overactive bladders (sensory urge and detrusor instability) were obtained before botulinum toxin injection and compared to those of 8 normally contractile, nonobstructed bladders obtained during radical cystectomy. Smoothelin mRNA expression patterns were investigated by Northern blot and variant specific reverse transcriptase-polymerase chain reaction as well as by quantitative reverse transcriptase-polymerase chain reaction on laser capture, microdissected smooth muscle. At the protein level smoothelin was investigated by standard and quantitative immunohistochemistry. RESULTS: The bladder muscularis expressed vascular and visceral smoothelin isoforms, and 2 of the known splice variants. In the smooth muscle of patients with detrusor instability and sensory urge a significant 2.4 and 2.2-fold increase, respectively, in smoothelin variant 1 mRNA was observed in comparison to that of normal controls. Analyses at the smoothelin protein level confirmed significant up-regulation in these bladder dysfunctions by a factor of 2.3 and 1.8, respectively. No significant difference in smoothelin expression was observed between detrusor instability and sensory urge. CONCLUSIONS: Increased expression of smoothelin in patients with detrusor instability and sensory urge implies that the etiology of these dysfunctions includes changes in myogenic parameters. In addition, our data support the new classification of the International Continence Society for overactive bladder proposing that sensory urge and detrusor instability represent a single clinical entity.

Strain typing of German transmissible spongiform encephalopathies field cases in small ruminants by biochemical methods.

Following the implementation of a large scale transmissible spongiform encephalopathies (TSE) surveillance programme of small ruminants, evidence for a natural transmission of bovine spongiform encephalopathy (BSE) to a French goat has been found. During the years 2002-2004, a massive TSE rapid testing programme on >250,000 small ruminants was carried out in Germany. In this national survey, 186 scrapie-affected sheep were found which originated from 78 flocks. The majority of these cases were of the classical TSE type (115 sheep belonging to 14 outbreaks). However, 71 cases coming from 64 flocks were of the novel atypical scrapie type. According to the regulation EU 999/2001, all TSE cases in small ruminants have to be examined by strain typing methods to explore any possibility of the existence of BSE cases in the field sheep population. Here we report on a biochemical typing strategy (termed FLI-test), which includes the determination of molecular masses, antibody binding affinities and glycosylation pattern of the TSE induced abnormal prion protein. Based on this typing approach none of the analysed German classical TSE outbreaks (total number of analysed sheep: 36) displayed biochemical features indicative for a BSE infection. However, in two cases distinct but BSE-unrelated PrP(Sc) types were found, which alludes to the existence of different scrapie strains in the German sheep population.

[International clinical recommendations on scar management]. / Internationale Klinische Empfehlungen zur Narbenbehandlung.

Many techniques for management of hypertrophic scars and keloids have been proven through extensive use, but few have been supported by prospective studies with adequate control groups. Several new therapies showed good results in small-scale trials, but these have not been repeated in larger trials with long-term follow-up. This article reports a qualitative overview of the available clinical literature by an international panel of experts using standard methods of appraisal. The article provides evidence- based recommendations on prevention and treatment of abnormal scarring and, where studies are insufficient, consensus on best practice. The recommendations focus on the management of hypertrophic scars and keloids, and are internationally applicable in a range of clinical situations. These recommendations support a move to a more evidence-based approach in scar management. This approach highlights a primary role for silicon gel sheeting and intralesional corticosteroids in the management of a wide variety of abnormal scars. The authors concluded that these are the only treatments for which sufficient evidence exists to make evidence-based recommendations. A number of other therapies that are in common use have achieved acceptance by the authors as standard practice. However, it is highly desirable that many standard practice and new emerging therapies undergo large-scale studies with long-term follow-up before being recommended conclusively as alternative therapies for scar management.