[Show abstract][Hide abstract] ABSTRACT: Stroke, broadly subdivided into ischemic and hemorrhagic subtypes, is a serious health-care problem worldwide. Previous studies have suggested ischemic and hemorrhagic stroke could present different functional recovery patterns. However, little attention has been given to this neurobiological finding. Coincidently, astrocyte morphology could be related to improved sensorimotor recovery after skilled reaching training and modulated by physical exercise and environmental enrichment. Therefore, it is possible that astrocyte morphology might be linked to differential recovery patterns between ischemic and hemorrhagic stroke. Thus, we decided to compare long-term GFAP-positive astrocyte morphology after ischemic (IS, n=5), hemorrhagic (HS, n=5) and sham (S, n=5) stroke groups (induced by endothelin-1, collagenase type IV-S and salina, respectively). Our results showed ischemic and hemorrhagic stroke subtypes induced similar long-term GFAP-positive astrocyte plasticity (P>0.05) for all evaluated measures (regional and cellular optical density; astrocytic primary processes ramification and length; density of GFAP positive astrocytes) in perilesional sensorimotor cortex and striatum. These interesting negative results discourage similar studies focused on long-term plasticity of GFAP-positive astrocyte morphology and recovery comparison of stroke subtypes.
Behavioural Brain Research 10/2014; · 3.39 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Tongue movements are critical for speech, swallowing, and respiration; and tongue dysfunction could lead to dysarthria, dysphagia, and obstructive sleep apnea, respectively. Our current understanding of the contributions of specific tongue muscles (TOs) to precise movement patterns is limited. Likewise, there is still little information regarding the orientation of histologic muscle fibers of the tongue in humans, especially between men and women. Thus, the aim of this study was to compare the histologic organization in the tongue of men and women. Ten tongues were studied in human specimens obtained from necropsies (five men and five women). The muscles were analyzed using histology, and the morphometric parameters were measured using Image Pro-Plus Software (Image Pro-Plus 6.0; Media Cybernetics, Silver Spring, MD). Slices were obtained from the anterior, median, and posterior parts of the tongue. We classified and estimated the percentages of transverse (T), oblique (O), and longitudinal (L) fibers in the tongue. To quantify the percentage of fibers in each category in the tongue, the shape coefficient (Shape Z) was estimated. Statistical differences were found between the orientation of the muscle fibers of men and women only for the middle region of the tongue. The middle region of the tongue in women compared with men has a smaller difference in the variation of the percentage of fibers T (P = 0.0004), O (P = 0.0006), and L (P = 0.0013). These morphologic findings are probably related to physiological differences.
[Show abstract][Hide abstract] ABSTRACT: Exercise training has neuroprotective effects whereas myocardial infarction (MI) and heart failure (HF) can cause neuronal death and reactive gliosis in the whole amygdala. The posterodorsal medial amygdala (MePD) is involved with cardiovascular reflexes and the central control of sympathetic/parasympathetic responses. Our aim was to study the effects of prior exercise training and of MI-induced HF on the neuronal and glial densities and the glial fibrillary acidic protein-immunoreactivity (GFAP-ir) in the MePD of adult male rats. Animals (n= 5/group) were: control, sedentary submitted to a sham MI (Sed Sham), sedentary submitted to MI/HF (Sed HF), trained on a treadmill and submitted to a sham MI (T Sham) or trained on a treadmill and submitted to MI/HF (T HF). The number of neurons and glial cells in the MePD was estimated using the optical fractionator and the GFAP-ir was quantified by optical densitometry. In the respective groups, treadmill training improved physical performance and MI damaged near 40% of the left ventricle. There was a hemispheric lateralization effect on the density of neurons (higher in the right MePD), but no significant difference in either the neuronal or the glial densities due to experimental condition. Regional GFAP-ir results revealed that the Sed HF group had a higher expression in the left MePD compared to the control and the Sed Sham rats (p⟨0.01). The present data did not evidence the effects of training or MI/HF in the MePD cellular density, but indicate a possible local restructuring of astrocytic cytoskeleton after MI/HF in rats.
Histology and histopathology 05/2014; · 2.24 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Lesions with great loss of skin and extensive burns are usually treated with heterologous skin grafts, which may lead rejection. Cell therapy with mesenchymal stem cells is arising as a new proposal to accelerate the healing process. We tested a new therapy consisting of sodium carboxymethylcellulose (CMC) as a biomaterial, in combination with adipose-derived stem cells (ADSCs), to treat skin lesions in an in vivo rat model. This biomaterial did not affect membrane viability and induced a small and transient genotoxicity, only at the highest concentration tested (40 mg/mL). In a rat wound model, CMC at 10 mg/mL associated with ADSCs increased the rate of cell proliferation of the granulation tissue and epithelium thickness when compared to untreated lesions (Sham), but did not increase collagen fibers nor alter the overall speed of wound closure. Taken together, the results show that the CMC is capable to allow the growth of ADSCs and is safe for this biological application up to the concentration of 20 mg/mL. These findings suggest that CMC is a promising biomaterial to be used in cell therapy.
PLoS ONE 01/2014; 9(5):e96241. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Oral squamous cell carcinoma (OSCC) is a public health problem. The hamster buccal pouch model is ideal for analyzing the development of OSCC. This research analysed the effects of sunitinib (tyrosine kinase inhibitor) in precancerous lesions induced by 7,12-dimethylbenz(a)anthracene (DMBA) in this model. Thirty-four male hamsters, divided into six groups: control-C (n = 7), acetone-A (n = 12), carbamide peroxide-CP (n = 5 ), acetone and CP-A+CP (n = 8), 1% DMBA in acetone and CP-DA+CP (n = 6), and 1% DMBA in acetone and CP and 4-week treatment with sunitinib-DA+CP+S (n = 7). The aspects evaluated were anatomopathological features (peribuccal area, paws, nose, and fur), histological sections of the hamster buccal pouches (qualitatively analyzed), epithelium thickness, and the rete ridge density (estimated). Sunitinib was unable to attenuate the decrease in weight gain induced by DMBA; no increase in volume was detected in the pouch and/or ulceration, observed in 43% of the animals in the DA+CP group. DA+CP groups presented a significant increase in rete ridge density compared to the control groups (P < 0.01) which was reverted by sunitinib in the DA+CP+S group. Sunitinib seems to have important benefits in early stage carcinogenesis and may be useful in chemoprevention.
[Show abstract][Hide abstract] ABSTRACT: It has been recently shown that enriched environment led to a significant benefit in learning and retention of visual-spatial memory, being able to reverse the cognitive impairment generated by undernourishment and recurrent seizures. We investigated the hippocampal morphological effects of recurrent seizures and undernourishment early in life in Wistar rats and the possible benefits produced by the enriched environment in these conditions. The morphological parameters stereologically evaluated were hippocampal volume, thickness of pyramidal stratum of the CA1 subfield and neuronal and glial densities in the same subfield. Male Wistar rats were divided into eight groups including nourished, nourished+enriched environment, nourished+recurrent seizures, nourished+recurrent seizures+enriched environment, undernourished, undernourished+enriched environment, undernourished+recurrent seizures and undernourished+recurrent seizures+ enriched environment. Undernourishement model consisted in nutritional deprivation regimen from post-natal day 2 (P2) to P15. From P8 to P10, recurrent seizures group were induced by flurothyl three times per day. Enriched environment groups were exposed between P21 and P51. Our main findings were: 1- Animals submitted to the enriched environment showed an increased hippocampal volume; 2- Enriched environment promotes increases in the thickness of the pyramidal layer in hippocampal CA1 subfield in animals nourished and undernourished with recurrent seizures; 3- Undernourishment during early development decreased neuronal density in CA1 and CA3 subfields. Our findings show that these three conditions induces important changes in hippocampal morphology, the most deleterious changes are induced by undernourishment and recurrent seizures, while more beneficial morphological changes are produced by enriched environment.
International journal of developmental neuroscience: the official journal of the International Society for Developmental Neuroscience 12/2013; · 2.03 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This study is a morphologic description of the recurrent laryngeal nerve (RLN) and of the number and size of motor units (MUs) in the thyroarytenoid (TA) muscle bilaterally of a human fetus aged 25 weeks. A quantitative analysis of RLN and MUs is presented to investigate similarities with equivalent structures in adults. In the fetus used in our study, the morphologic organization of the RLN was similar to that commonly described in the adult RLN. Moreover, as is observed in adult TA, the TA of the analyzed fetus, particularly the right TA, showed MUs typical of muscles with great motor accuracy. These results may be used to increase our knowledge of the features of the voice in adults and newborns.
Journal of voice : official journal of the Voice Foundation. 10/2013;
[Show abstract][Hide abstract] ABSTRACT: The g-ratio (estimated by dividing the axon diameter by the myelinated fiber diameter) can be useful to the evaluation of the relationship between nerve conduction velocity and fiber morphology during peripheral nerve regeneration. However, there is little detailed information about the g-ratio of the human recurrent laryngeal nerve (RLN), especially between men and women. The objective of this study was to investigate the g-ratio of the RLN by quantifying histomorphometric data (axon diameter and myelinated fiber diameter) in the RLN of men and women. The RLN was bilaterally studied in human specimens obtained from necropsies (seven men and seven women). The nerves were analyzed using histology, and the morphometric parameters were measured using Image Pro-Plus Software (Image Pro-Plus 6.0; Media Cybernetics, Silver Spring, MD, USA). When compared with the RLN of the women, the parameters of the RLN of the men are significantly larger, as shown by the axon diameter (19.0 %) (P = 0.0001), myelinated fiber diameter (7.1 %) (P = 0.0497), and g-ratio (12.5 %) (P = 0.0005). Our findings demonstrated that there are morphological asymmetries between the g-ratio (degree of the myelination) of the masculine and feminine RLN. These morphological findings are probably related to physiological differences.
Archives of Oto-Rhino-Laryngology 09/2013; · 1.61 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objective: The present study evaluated HLA-G gene polymorphisms in patients with aggressive periodontitis (AP), chronic periodontitis (CP) and healthy controls.
Methods: The insertion/deletion (ins/del) polymorphism of 14 bp and a single nucleotide polymorphism (SNP) C>G on the position +3142 of the 3’ untranslated region (UTR) of the gene were analyzed in AP (n=24), CP (n=62) patients and healthy control (n=47).
Results: It was observed a significant deviation from Hardy–Weinberg expectations in the CP group, considering the 14 bp ins/del, but not in the others groups. No significant deviations were observed in patients and control groups considering the +3142 C>G SNP. In the CP group it was observed a significantly increased frequency of homozygotes for the 14 bp del allele as compared to controls. The CP group presented a higher frequency of the del allele, which was marginally not significant. Concerning this polymorphism, no significant differences were observed between the AP and healthy control groups. No significant differences were observed among patients and controls when considering the +3142 C>G SNP frequencies. An increased frequency of the del/G haplotype in CP patients and a decreased frequency of the ins/G haplotype with no statistical significance.
Conclusion: No differences were found among patients (CP and AG) and controls when considering the +3142 C>G SNP haplotypes frequencies, but a significant increased frequency of homozygotes for the 14 bp del allele was observed in CP patients compared to healthy controls, suggesting a susceptibility role of this polymorphism in the pathogenesis of this condition.
IADR/AADR/CADR General Session and Exhibition 2013; 03/2013
[Show abstract][Hide abstract] ABSTRACT: This study investigated the sexual dimorphism in the recurrent laryngeal nerve (RLN) and thyroarytenoid (TA) muscle, which control the vocal fold. The RLN and TA were bilaterally studied in human specimens obtained from necropsies (seven men and seven women). Analysis of the morphometric parameters showed that the RLN of the men were significantly larger, as shown by the intraperineural area (42.5%) (P=0.006), total number of fibers (38.0%) (P=0.0002), axonal area (34.3%) (P=0.0001), axonal diameter (19.0%) (P=0.0001), and the area of the nerve occupied by myelinated fibers (34.9%) (P=0.001). By contrast, in women, our results showed that the area of the RLN occupied by endoneurial connective tissue was larger (5.7%) (P=0.001). Estimation of the fiber area and shape coefficient showed that the histologic organization of TA is similar in men and women. These results may contribute toward enhancing our understanding about the voice neurobiology.
Journal of voice: official journal of the Voice Foundation 02/2013; · 0.95 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Stroke causes disability and mortality worldwide and is divided into ischemic and hemorrhagic subtypes. Although clinical trials suggest distinct recovery profiles for ischemic and hemorrhagic events, this is not conclusive due to stroke heterogeneity. The aim of this study was to produce similar brain damage, using experimental models of ischemic (IS) and hemorrhagic (HS) stroke and evaluate the motor spontaneous recovery profile. We used 31 Wistar rats divided into the following groups: Sham (n=7), ischemic (IS) (n=12) or hemorrhagic (HS) (n=12). Brain ischemia or hemorrhage was induced by endotelin-1 (ET-1) and collagenase type IV-S (collagenase) microinjections, respectively. All groups were evaluated in the open field, cylinder and ladder walk behavioral tests at distinct time points as from baseline to 30 days post-surgery (30 PS). Histological and morphometric analyses were used to assess the volume of lost tissue and lesion length. Present results reveal that both forms of experimental stroke had a comparable long-term pattern of damage, since no differences were found in volume of tissue lost or lesion size 30 days after surgery. However, behavioral data showed that hemorrhagic rats were less impaired at skilled walking than ischemic ones at 15 and 30 days post-surgery. We suggest that experimentally comparable stroke design is useful because it reduces heterogeneity and facilitates the assessment of neurobiological differences related to stroke subtypes; and that spontaneous skilled walking recovery differs between experimental ischemic and hemorrhagic insults.
Behavioural brain research 02/2013; 244C:82-89. · 3.22 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Physical exercise has an important influence on brain plasticity, which affects the neuron-glia interaction. Astrocytes are susceptible to plasticity, and induce and stabilize synapses, regulate the concentration of various molecules, and support neuronal energy metabolism. The aim of our study was to investigate whether physical exercise is capable of altering the morphology, density and expression of glial fibrillary acidic protein (GFAP) in astrocytes from the CA1 region of rat hippocampus. Thirteen male rats were divided in two groups: sedentary (n = 6) and exercise (n = 7). The animals in the exercise group were submitted to a protocol of daily physical exercise on a treadmill for four consecutive weeks. GFAP immunoreactivity was evaluated using optical densitometry and the morphological analyses were an adaptation of Sholl's concentric circles method. Our results show that physical exercise is capable of increasing the density of GFAP-positive astrocytes as well as the regional and cellular GFAP expression. In addition, physical exercise altered astrocytic morphology as shown by the increase observed in the degree of ramification in the lateral quadrants and in the length of the longest astrocytic processes in the central quadrants. Our data demonstrate important changes in astrocytes promoted by physical exercise, supporting the idea that these cells are involved in regulating neural activity and plasticity.
Brain Structure and Function 01/2013; · 7.84 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Extra-pyramidal symptoms (EPS) such as akinesia, dystonia, gait alteration and tremors are observed when dopamine D2-receptors are blocked by pharmacological agents such as haloperidol. These alterations produce a Parkinson disease-like state (PLS). Physical exercise has been proven to improve gait and locomotor symptoms in Parkinson´s disease; we sought to elucidate the effects of physical exercise on PLS induced by chronic administration of haloperidol in rats. We used 48 rats distributed into four groups: Control, Exercise, Haloperidol, and Hal+ Exe. All the animals received a daily injection of saline or haloperidol for 30 days, and the exercise groups underwent a daily 30-minute exercise protocol for 20 days. The animals were subjected to the ink-paw test, bar test and open-field test throughout the training period. The haloperidol-induced akinesia increased throughout the days of injections, but exercise was shown to alleviate it. The assessment showed shortened stride length and increased stance width with the use of haloperidol, which were significantly alleviated by exercise. These results indicate that exercise could be an interesting approach towards reducing unwanted EPS caused by haloperidol.
Pharmacology Biochemistry and Behavior 01/2013; · 2.82 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Glutaric aciduria type I (GA-I) is characterized by accumulation of glutaric acid (GA) and neurological symptoms, such as cognitive impairment. Although this disease is related to oxidative stress and inflammation, it is not known whether these processes facilitate the memory impairment. Our objective was to investigate the performance of rat pups chronically injected with GA and lipopolysaccharide (LPS) in spatial memory test, antioxidant defenses, cytokines levels, Na+, K+-ATPase activity, and hippocampal volume. We also evaluated the effect of N-acetylcysteine (NAC) on theses markers.
Rat pups were injected with GA (5umol g of body weight-1, subcutaneously; twice per day; from 5th to 28th day of life), and were supplemented with NAC (150mg/kg/day; intragastric gavage; for the same period). LPS (2mg/kg; E.coli 055 B5) or vehicle (saline 0.9%) was injected intraperitoneally, once per day, from 25th to 28th day of life. Oxidative stress and inflammatory biomarkers as well as hippocampal volume were assessed.
GA caused spatial learning deficit in the Barnes maze and LPS potentiated this effect. GA and LPS increased TNF-α and IL-1β levels. The co-administration of these compounds potentiated the increase of IL-1β levels but not TNF-α levels in the hippocampus. GA and LPS increased TBARS (thiobarbituric acid-reactive substance) content, reduced antioxidant defenses and inhibited Na+, K+-ATPase activity. GA and LPS co-administration did not have additive effect on oxidative stress markers and Na+, K+ pump. The hippocampal volume did not change after GA or LPS administration. NAC protected against impairment of spatial learning and increase of cytokines levels. NAC Also protected against inhibition of Na+,K+-ATPase activity and oxidative markers.
These results suggest that inflammatory and oxidative markers may underlie at least in part of the neuropathology of GA-I in this model. Thus, NAC could represent a possible adjuvant therapy in treatment of children with GA-I.
PLoS ONE 01/2013; 8(10):e78332. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVE: We studied transplants of bone marrow mononuclear cells (BMMC) by lumbar puncture (LP) in a severe model of spinal cord injury (SCI) using clip compression.METHODS: BMMCs or saline solution were transplanted by LP 48 hours and 9 days post injury. Motor function was evaluated by BBB scale, histological analysis by Nissl technique and the verification of cell migration by PCR analysis.RESULTS: The BBB had significantly improved in rats treated with BMMCs by LP compared with controls (p<0.001). The histological analysis did not showed difference in the lesional area between the groups. The PCR analysis was able to found BMMCs in the injury site. CONCLUSIONS: two BMMC transplants by LP improved motor function in a severe model of SCI and BMMC was found in the injury site.
[Show abstract][Hide abstract] ABSTRACT: This study is the first detailed qualitative morphologic description of the vocal fold and its associated structures (false vocal fold, larynx ventricle, epithelium, mucous glands, blood vessels, and vocal ligament) of a human fetus aged 25 weeks. In addition, a quantitative analysis of thyroarytenoid (TA) muscle fiber orientation is presented to investigate similarities with adult TA. Histologic cross sections from the vocal fold and the anterior, middle, and posterior regions of the TA muscle were examined bilaterally, and both qualitative and quantitative analyses show that the vocal fold and most of the associated structures are completely established in the studied sample.
Journal of voice: official journal of the Voice Foundation 11/2012; · 0.95 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Abstract Objective. The present study evaluated the Th1/Th2 cytokine profile in plasma from healthy controls and different types of periodontitis patients. Materials and methods. The concentration of IL-2, IL-4, IL-5, IL-10, TNF-α and IFN-γ was determined in healthy controls (n = 18) and patients with chronic (n = 19) and aggressive periodontitis (n = 19) using a flow cytometric multiplex immunoassay. Means and standard deviations were calculated and compared using Kruskal-Wallis test. Spearman rho coefficient was used to correlate cytokines in the studied groups. Results. Although there was no significant difference in the concentration of cytokines between groups, there was a tendency to lower levels of IL-5 and IL-10 in the aggressive periodontitis group. Stronger correlations were observed between IL-2/IL-4 and IL-2/IL-10 in healthy controls (0.938 and 0.669, respectively) compared with chronic (0.746 and 0.532) and aggressive periodontitis groups (0.395 and 0.266). When compared to healthy (0.812) and chronic periodontitis (0.845) groups, the correlation of IL-4/IL-5 was weaker in the aggressive group (0.459). Conclusion. No difference between systemic levels of Th1/Th2 was observed. In aggressive periodontitis patients, nevertheless, a trend towards low levels of Th2 cytokines could suggest a contribution to the development of such an exacerbated manifestation of this disease.
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to evaluate the effects of treadmill training on nociceptive sensitivity and immunoreactivity to calcitonin gene-related peptide in the dorsal horn of the spinal cord of diabetic rats.
Male Wistar rats were divided into three groups: control, diabetic and trained diabetic. Treadmill training was performed for 8 weeks. The blood glucose concentrations and body weight were evaluated 48 h after diabetes induction and every 30 days thereafter. The nociceptive sensitivity was evaluated using the tail-flick apparatus. The animals were then transcardially perfused, and the spinal cords were post-fixed, cryoprotected and sectioned in a cryostat. Immunohistochemistry for calcitonin gene-related peptide analysis was performed on the dorsal horn of the spinal cord.
The nociceptive sensitivity analysis revealed that, compared with the control and trained diabetic animals, the latency to tail deflection on the apparatus was longer for the diabetic animals. Optical densitometry demonstrated decreased calcitonin gene-related peptide immunoreactivity in the dorsal horn of the spinal cord in diabetic animals, which was reversed by treadmill training.
We concluded that treadmill training can alleviate nociceptive hypoalgesia and reverse decreased calcitonin gene-related peptide immunoreactivity in the dorsal horn of the spinal cord of diabetic animals without pharmacological treatment.
Clinics (São Paulo, Brazil) 09/2012; 67(9):1087-91. · 1.59 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Following heart failure (HF), immune activation leads to an imbalance between pro-inflammatory and anti-inflammatory cytokines. Low-level laser therapy (LLLT) has been used as an anti-inflammatory treatment in several disease conditions. However, the effect of LLLT on the skeletal muscle of rats with HF remains unclear. The present report aimed to evaluate the influence of LLLT on the inflammatory profile of rats with HF. The left coronary artery was ligated to induce HF and a sham operation was performed in the control groups. Male Wistar rats (n = 49) were assigned to one of six groups: placebo sham rats (P-Sham; n = 8), LLLT at a dose of 3 J/cm(2) sham rats (3 J/cm(2)-Sham; n = 8), LLLT at a dose of 21 J/cm(2) sham rats (21 J/cm(2)-Sham; n = 8), placebo HF rats (P-HF; n = 9), LLLT at a dose of 3 J/cm(2) HF rats (3 J/cm(2)-HF; n = 8), and LLLT at a dose of 21 J/cm(2) HF rats (21 J/cm(2)-HF; n = 8). Four weeks after myocardial infarction or sham surgery, rats were subjected to LLLT (InGaAlP 660 nm, spot size 0.035 cm(2), output power 20 mW, power density 0.571 W/cm(2), energy density 3 or 21 J/cm(2), exposure time 5.25 s and 36.75 s) on the right gastrocnemius for 10 consecutive days. LLLT reduced plasma IL-6 levels (61.3 %; P < 0.01), TNF-α/IL-10 (61.0 %; P < 0.01) and IL-6/IL-10 ratios (77.3 %; P < 0.001) and increased IL-10 levels (103 %; P < 0.05) in the 21 J/cm(2)-HF group. Moreover, LLLT reduced the TNF-α (20.1 % and 21.3 %; both P < 0.05) and IL-6 levels (54.3 % and 37.8 %; P < 0.01 and P < 0.05, respectively) and the IL-6/IL-10 ratio (59.7 % and 42.2 %; P < 0.001 and P < 0.05, respectively) and increased IL-10 levels (81.0 % and 85.1 %; both P < 0.05) and the IL-10/TNF-α ratio (171.5 % and 119.8 %; P < 0.001 and P < 0.05, respectively) in the gastrocnemius in the 3 J/cm(2)-HF and 21 J/cm(2)-HF groups. LLLT showed systemic and skeletal muscle anti-inflammatory effects in rats with HF.
Lasers in Medical Science 08/2012; · 2.42 Impact Factor