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To evaluate the neurovascular bundle preservation grades during robotic-assisted radical prostatectomy and compared to the trifecta combined outcome (oncologic control, continence, and sexual function) twelve months after the surgery.Cohort of patients who underwent nerve-sparing robotic-assisted radical prostatectomy had the neurovascular bundle preservation retrospectively graded from 0 to 8 according to the Hopkins subjective visual classification. Patients then were divided into two groups, according to the median of nerve-sparing grading: those with score six or high and those with score less than six. Main outcome was the trifecta combined outcome and secondary outcomes was the individual trifecta criteria (prospective analysis). A secondary analysis with groups divided according to pre-operatory SHIM score was made.One hundred robotic-assisted nerve-sparing radical prostatectomy were performed, of which 83 were included. There were 53 patients with grading greater than or equal to six (group 1) and 30 patients less than six (group 2). 66.6% patients (35/53) in group 1 had a trifecta combined outcome of compared to 33.3% (10/30) in group 2 (p = 0.017). Individually, the erectile function was higher in group 1 (73.6%) compared to group 2 (46.7%) (p = 0.014). Both the results of the combined endpoint trifecta and erection were also maintained in the group with preoperative SHIM ≥ 17.The grading of preservation of the neurovascular bundle in radical prostatectomy is related to a better combined trifecta outcome one year after surgery.

The establishment of giardiasis, a disease caused by the protozoan parasite Giardia lamblia, starts with the adhesion of trophozoites to the surface of host intestinal epithelial cells. Trophozoites then replicate and colonize the gastrointestinal tract, eliciting multiple biological responses in their hosts. The interactions between the host organism and parasite can be evaluated by a variety of in vivo and in vitro means. Proper detection and treatment of giardiasis require a thorough understanding of the molecular mechanisms of the disease course from the onset of infection through establishment of chronic disease. This article reviews a collection of recent studies to provide an overview of the advances that have been made over the past 5 years (2015–2020) in establishing a stronger understanding of the molecular basis of Giardia-host interactions, with a particular emphasis on the use of in vitro techniques. The outcome of pathogen-host association produced several effector mechanisms critical to parasite survival/replication and to control of infection by the host. These included differential gene expression, regulation of the intestinal barrier function (expression/location of tight junction proteins, mucus turnover, cell apoptosis), and alterations of GIT microbial community. Understanding of giardiasis has progressed rapidly through the use of in vitro means of experimentation during the period from 2015 to 2020. The discovery of new molecular networks in Giardia-host interactions from both perspectives contributed to a more comprehensive understanding of giardiasis.

To present a large series ears with tympanic membrane perforations (TMP), to describe their characteristics, and to propose a new classification system based on the pathogenesis of TMP. This cross-sectional study was conducted at a tertiary university hospital with 1003 ears (792 consecutive patients with TMP in at least 1 ear). Otoendoscopy and audiometry were performed. Perforation measurements and their locations were digitally assessed. TMP with no suggestive signs of previous retraction were classified as Group 1, and those with possible previous retraction were classified as Group 2. Signs of retraction previous to the TMP, symptom length, perforation size and location, status of the contralateral ear, and hearing status were compared. Group 1 comprised 63.5% of the included ears. Compared to Group 2, Group 1 presented a higher rate of central perforations (99% vs. 53%), a shorter duration of symptoms, smaller perforations (mean area: 18.5% vs. 41.4%), a higher rate of perforations in the anterior quadrants, better hearing levels (mean tritonal gap: 23.9 dB vs. 29.2 dB), and a lower rate of abnormal contralateral ears (28% vs. 66%). The classification of TMP into two groups based on signs of previous retractions is feasible and indicates two different levels of disease severity. While the group without previous signs of retraction comprises ears with more limited disease, membranes with previous retraction seem to show more severe disease and, consequently, a less functional middle ear.

Intraoperative blood salvage (IBS) with autologous blood transfusion is controversial in liver transplantation (LT) for hepatocellular carcinoma (HCC). This study evaluated the role of IBS usage in LT for HCC. In a retrospective cohort study at a single center from 2002 to 2018, the outcomes of LT surgery for HCC were analyzed. Overall survival and disease-free survival of patients who received IBS were compared with those who did not receive IBS. Cancer recurrence, length of hospital stay, post-transplant complications, and blood loss also were evaluated. The primary aim of this study was to evaluate overall mid-term and long-term survival (4 and 6 years, respectively). Of the total 163 patients who underwent LT for HCC in the study period, 156 had complete demographic and clinical data and were included in the study. IBS was used in 122 and not used in 34 patients. Ninety-five (60.9%) patients were men, and the mean patient age was 58.5 ± 7.6 years. The overall 1-year, 5-year, and 7-year survival in the IBS group was 84.2%, 67.7%, and 56.8% vs. 85.3%, 67.5%, and 67.5% in the non-IBS group (p = 0.77). The 1-year, 5-year, and 7-year disease-free survival in the IBS group was 81.6%, 66.5%, and 55.4% vs. 85.3%, 64.1%, and 64.1% in the non-IBS group (p = 0.74). For patients without complete HCC necrosis (n = 121), the 1-year, 5-year, and 7-year overall survival rates for those who received IBS (n = 95) were 86.2%, 67.7%, and 49.6% vs. 84.6%, 70.0%, and 70.0% for 26 patients without IBS (p = 0.857). For the same patients, the 1-year, 5-year, and 7-year disease-free survival in the IBS group was 84.0%, 66.8%, and 64.0% vs. 88.0%, 72.8%, and 72.8% in the non-IBS group (p = 0.690). IBS does not appear to be associated with worse outcomes in patients undergoing LT for HCC, even in the presence of viable HCC in the explant. There seems to be no reason to contraindicate the use of IBS in LT for HCC.

Mutations in the RNA-binding protein (RBP) FUS have been genetically associated with the motoneuron disease amyotrophic lateral sclerosis (ALS). Using both human induced pluripotent stem cells and mouse models, we found that FUS-ALS causative mutations affect the activity of two relevant RBPs with important roles in neuronal RNA metabolism: HuD/ELAVL4 and FMRP. Mechanistically, mutant FUS leads to upregulation of HuD protein levels through competition with FMRP for HuD mRNA 3’UTR binding. In turn, increased HuD levels overly stabilize the transcript levels of its targets, NRN1 and GAP43. As a consequence, mutant FUS motoneurons show increased axon branching and growth upon injury, which could be rescued by dampening NRN1 levels. Since similar phenotypes have been previously described in SOD1 and TDP-43 mutant models, increased axonal growth and branching might represent broad early events in the pathogenesis of ALS., Maria Giovanna Garone et al. use iPSC and mouse models to evaluate a mechanistic link between aberrant axonal phenotypes in ALS and the alteration of a cross-regulatory circuitry involving three RNA binding proteins: FUS, HuD and FMRP. Their results suggest NRN1 as a potential therapeutic target for ALS and provide further insight into the pathogenesis of this critical disorder.

Fragile X syndrome (FXS) is a neurodevelopmental disorder, characterized by intellectual disability and sensory deficits, caused by epigenetic silencing of the FMR1 gene and subsequent loss of its protein product, fragile X mental retardation protein (FMRP). Delays in synaptic and neuronal development in the cortex have been reported in FXS mouse models; however, the main goal of translating lab research into pharmacological treatments in clinical trials has been so far largely unsuccessful, leaving FXS a still incurable disease. Here, we generated 2D and 3D in vitro human FXS model systems based on isogenic FMR1 knock-out mutant and wild-type human induced pluripotent stem cell (hiPSC) lines. Phenotypical and functional characterization of cortical neurons derived from FMRP-deficient hiPSCs display altered gene expression and impaired differentiation when compared with the healthy counterpart. FXS cortical cultures show an increased number of GFAP positive cells, likely astrocytes, increased spontaneous network activity, and depolarizing GABAergic transmission. Cortical brain organoid models show an increased number of glial cells, and bigger organoid size. Our findings demonstrate that FMRP is required to correctly support neuronal and glial cell proliferation, and to set the correct excitation/inhibition ratio in human brain development.

Many crowd analysis methods rely on optical flow techniques to estimate the main moving directions. In this work, we propose a crowd flow filtering approach for calibrated cameras that can be coupled to any generic optical flow method. It projects the input optical flow to the world coordinate system, performs a local motion analysis exploring a Social Forces Model and then projects the filtered flow back onto the image plane. The method was tested on publicly available datasets involving crowded scenarios used in conjunction with different optical flow methods, and results indicate that the proposed filtering method provides coherent crowd flows when coupled to the tested methods.

The objective of this is to verify whether the hearing impairment caused by posterior epitympanic differed from that caused by posterior mesotympanic cholesteatomas by a cross-sectional study. We evaluated 264 ears of patients with cholesteatoma, who had not been subjected to ear surgery. Otoendoscopy and pure-tone audiometry were performed. Analyzed route involved in cholesteatoma formation: posterior epitympanic or posterior mesotympanic, air-bone gaps at 512-4000 Hz and pure-tone averages. The mean age of the patients enrolled in this study was 33.8 years, and 51.8 % of them was male. Posterior epitympanic cholesteatoma was found in 50.4 % of the study population. When the air-bone gaps were compared, the mesotympanic group had greater thresholds at 500, 2000 Hz, and a greater pure-tone average (P = 0.003, P = 0.03, and P = 0.02, respectively). Posterior mesotympanic cholesteatoma showed greater air-bone gaps thresholds at the speech frequencies than posterior epitympanic cholesteatoma did. Moreover, the two growth patterns were very similar with regard to all other audiometric parameters analyzed in this study.

According to the current criteria, the diagnosis of early allograft dysfunction usually cannot be established before the end of the first week after liver transplantation. Thus, early predictive tests for detecting allograft dysfunction are still warranted to prevent allograft failure. This study was undertaken to assess the role of low serum factor V activity as an early prognostic factor (postoperative day 2) after liver transplantation.A retrospective review of all consecutive adult patients who underwent first orthotopic whole-graft liver transplant at our institution between March 2002 and June 2011 was undertaken. Primary endpoint was graft failure within 90 days after transplantation.Of all 105 patients analyzed in this study, 39 (37.1 %) were female and 66 (62.9 %) were male. Mean age was 52.7 ± 11.7 years, and median follow-up period was 2474 ± 164 days. There were overall 33 (31.4 %) deaths, 13 of those occurring on the first 90 post-transplant days. Multivariate analysis demonstrated that serum factor V lower than 41.5 % and female gender had a negative impact not only on allograft failure/death within 90 days after transplantation (RR = 5.30, CI = 1.40-20.2, p = 0.015 and RR = 5.23, CI = 1.53-21.33, p = 0.008) but also on overall mortality. For prediction of allograft failure/death occurring during the first 3 months, serum factor V level of 41.5 % or lower exhibited a specificity of 87.9 %, a sensitivity of 42.9 %, an accuracy of 81.9 %, a positive predictive value of 35.3 %, and a negative predictive value of 90.9 %.Assessment of serum factor V levels on postoperative day 2 might be a promising prognostic tool for early prediction of inferior outcomes after liver transplantation.

Background Cancer is a mosaic of tumor cell subpopulations, where only a minority is responsible for disease recurrence and cancer invasiveness. We focused on one of the most aggressive circulating tumor cells (CTCs) which, from the primitive tumor, spreads to the central nervous system (CNS), evaluating the expression of prognostic and putative cancer stem cell markers in breast cancer (BC) leptomeningeal metastasis (LM). Methods Flow cytometry immunophenotypic analysis of cerebrospinal fluid (CSF) samples (4.5 ml) was performed in 13 consecutive cases of BCLM. Syndecan-1 (CD138), MUC-1 (CD227) CD45, CD34, and the putative cancer stem cell markers CD15, CD24, CD44, and CD133 surface expression were evaluated on CSF floating tumor cells. The tumor-associated leukocyte population was also characterized. Results Despite a low absolute cell number (8 cell/μl, range 1–86), the flow cytometry characterization was successfully conducted in all the samples. Syndecan-1 and MUC-1 overexpression was documented on BC cells in all the samples analyzed; CD44, CD24, CD15, and CD133 in 77%, 75%, 70%, and 45% of cases, respectively. A strong syndecan-1 and MUC-1 expression was also documented by immunohistochemistry on primary breast cancer tissues, performed in four patients. The CSF tumor population was flanked by T lymphocytes, with a different immunophenotype between the CSF and peripheral blood samples (P ≤ 0.02). Conclusions Flow cytometry can be successfully employed for solid tumor LM characterization even in CSF samples with low cell count. This in vivo study documents that CSF floating BC cells overexpress prognostic and putative cancer stem cell biomarkers related to tumor invasiveness, potentially representing a molecular target for circulating tumor cell detection and LM treatment monitoring, as well as a primary target for innovative treatment strategies. The T lymphocyte infiltration, documented in all CSF samples, suggests a possible involvement of the CNS lymphatic system in both lymphoid and cancer cell migration into and out of the meninges, supporting the extension of a new form of cellular immunotherapy to LM. Due to the small number of cases, validation on large cohorts of patients are warranted to confirm these findings and to evaluate the impact and value of these results for diagnosis and management of LM. Electronic supplementary material The online version of this article (doi:10.1186/s13058-017-0827-4) contains supplementary material, which is available to authorized users.

Glycerol represents an important metabolite for the control of lipid accumulation and hepatic gluconeogenesis. We investigated whether hepatic expression and functionality of aquaporin-9 (AQP9), a channel mediating glycerol influx into hepatocytes, is impaired in non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH) in the context of insulin resistance.Liver biopsies were obtained from 66 morbid obese patients undergoing bariatric surgery (66% women, mean body mass index (BMI) 46.1±1.0 kg m(-2)) with available liver echography and pathology analysis of the biopsies in this cross-sectional study. Subjects were classified according to normoglycemia (NG), impaired glucose tolerance (IGT) or type 2 diabetes (T2D). Hepatic expression of AQP9 was analyzed by real-time PCR, western blotting and immunohistochemistry, while glycerol permeability (P(gly)) was measured by stopped-flow light scattering.AQP9 was the most abundantly (P0.0001) expressed aquaglyceroporin in human liver (AQP9AQP3AQP7AQP10). Obese patients with T2D showed increased plasma glycerol as well as lower P(gly) and hepatic AQP9 expression. The prevalence of NAFLD and NASH in T2D patients was 100 and 65%, respectively. Interestingly, AQP9 expression was decreased in patients with NAFLD and NASH as compared with those without hepatosteatosis, in direct relation to the degree of steatosis and lobular inflammation, being further reduced in insulin-resistant individuals. The association of AQP9 with insulin sensitivity was independent of BMI and age. Consistent with these data, fasting insulin and C-reactive protein contributed independently to 33.1% of the hepatic AQP9 mRNA expression variance after controlling for the effects of age and BMI.AQP9 downregulation together with the subsequent reduction in hepatic glycerol permeability in insulin-resistant states emerges as a compensatory mechanism whereby the liver counteracts further triacylglycerol accumulation within its parenchyma as well as reduces hepatic gluconeogenesis in patients with NAFLD.

This paper presents an approach for object tracking based on multiple disjoint patches. Initially, the target is subdivided into a set of rectangular patches, and each patch is represented parametrically by the mean vector and covariance matrix computed from a set of feature vectors that represent each pixel of the target. Each patch is tracked independently based on the Bhattacharyya distance, and the displacement of the whole template is obtained using a Weighted Vector Median Filter (WVMF), which reduces the influence of incoherently tracked patches. To smooth the obtained trajectory and also cope with short-term total occlusions, a predicted displacement vector based on the motion of the target in the previous frames is also used, and an updating scheme is applied to deal with appearance changes of the template. Experimental results indicate that the proposed scheme is robust to partial and short-time total occlusions, presenting a good compromise between accuracy and execution time when compared to other approaches.

Current guidelines recommend the assessment of at least 12 lymph nodes for rectal cancer staging. Preoperative chemoradiotherapy may affect lymph node yield in this malignancy. This study investigated the impact of neoadjuvant chemoradiotherapy on the number of lymph nodes retrieved from rectal cancer patients.An analysis of 162 rectal cancer patients who underwent curative surgery between 2005 and 2010. Seventy-one patients with stage II or III tumors received preoperative chemoradiotherapy. Using multivariate analysis, we assessed the correlation between clinicopathologic variables and number of retrieved lymph nodes. We also evaluated the association between survival and number of lymph nodes obtained.On multivariate analysis, preoperative chemoradiotherapy was the only variable to independently affect the number of lymph nodes obtained. The mean number of lymph nodes was 14.2 in patients treated with preoperative chemoradiotherapy and 19.4 in those not treated (P 0.001). In the chemoradiotherapy group, 29.6 % of patients had fewer than 12 lymph nodes obtained compared with 9.9 % in the primary surgery group (P = 0.003). After chemoradiation, the number of retrieved lymph nodes was inversely correlated with tumor regression grade. Results showed that 5-year overall and disease-free survival were similar whether the patient had 12 or more nodes retrieved or not.Preoperative chemoradiotherapy reduces the lymph node yield in rectal cancer. The number of retrieved lymph nodes is affected by degree of histopathologic response of the tumor to chemoradiation. Thus, number of lymph nodes should not be used as a surrogate for oncologic adequacy of resection after neoadjuvant chemoradiotherapy for rectal cancer.

The aim of this study was to determine the effects of the synthetic auxin 3,5,6-trichloro-2-pirydiloxyacetic acid (3,5,6-TPA) on photosynthetic activity, photosynthate transport to the fruit, and fruitlet abscission to further explain the physiological basis of auxin-mediated citrus fruit thinning. Applying 15 mg l(-1) 3,5,6-TPA to trees during the fruit cell division stage significantly increased fruitlet abscission of Clementine mandarin. On treated trees, abnormal foliar development and photosynthetic damage were observed at the same time as 3,5,6-TPA reduced fruitlet growth rate. Briefly, treatment reduced chlorophyll and carotenoid concentrations and modified chlorophyll a fluorescence parameters, that is, reduced the quantum yield (Dcurrency signPSII) of the noncyclic electron transport rate, diminished the capacity to reduce the quinone pool (photochemical quenching; q(p)), and increased nonphotochemical quenching (q (N)), thereby preventing the dissipation of excess excitation energy. In addition, the net photosynthetic flux (mu mol CO2 m(-2) s(-1)) and leaf photosynthate content decreased in treated trees. As a result, the 3,5,6-TPA treatment significantly reduced the photosynthate accumulation in fruit from day 3 to day 8 after treatment, thus reducing fruitlet growth rate. Hence, treated fruitlets significantly increased ethylene production and abscised. Twenty days after treatment, chlorophyll a fluorescence parameters and fruitlet growth rate were reestablished. Accordingly, the thinning effect of 3,5,6-TPA may be due to a temporarily induced photosynthetic disorder that leads to reduction in photosynthate production and fruitlet uptake that temporarily slows its growth, triggering ethylene production and fruitlet abscission. Afterward, the remaining treated fruit overcame this effect, increased growth rate, and reached a larger size than control fruit.

RC-3095, a synthetic gastrin-releasing peptide (GRP) antagonist, has been identified as a candidate compound for the treatment of tumor necrosis factor (TNF)-dependent chronic inflammatory conditions.The aim of this study was to evaluate the effects of RC-3095 in a rat model of ulcerative colitis.Ninety Wistar rats were included in the study. Colitis was induced by a single intracolonic application of acetic acid. Rats were divided into three groups of treatment: subcutaneous RC-3095, intracolonic mesalazine, and subcutaneous dexamethasone. Additionally, there was a fourth group of animals submitted to induction of colitis without receiving any form of treatment, and a fifth group in which no colitis was induced. Seventy-two hours after instillation of acetic acid, the animals were killed and the following parameters were assessed: morphological score of damage, histological score of colonic inflammation, and immunohistochemical expression of TNF-alpha and interleukin (IL)-1beta.RC-3095 was the only treatment to significantly reduce macroscopic and microscopic scores of inflammation as compared with the animals from the non-treated colitis group. RC-3095 also significantly reduced the colonic expression of TNF-alpha, but not the expression of IL-1beta.RC-3095 reduced the colitis severity in a well-established experimental model of IBD. The anti-inflammatory activity of this compound was associated with a reduction in the colonic expression of TNF-alpha. These results suggest that interference with GRP pathway might represent a potential new strategy for the treatment of ulcerative colitis that deserves further investigational studies.

The quantification of angiogenesis and metalloproteinases may be useful in cholesteatoma behavior assessment as markers of its aggressiveness. The objective of this study is to compare markers CD31, MMP2 and MMP9 in pediatric and adult patients. This study is based on cross-sectional studies of pediatric (or=18 years old) and adult groups (or=19 years old). Samples of 120 cholesteatomas were fixed in 10% formol, prepared on five slides of each sample through habitual histological techniques, and number of blood vessels (CD31), marking with MMP2 and MMP9, number of matrix cells and thickness at perimatrix cell were observed. Data were analyzed through SPSS using Spearman and Mann-Whitney coefficients. Cholesteatomas were equally distributed: 60 in pediatric patients (11.77 +/- 3.57 years); 60 in adult patients (38.29 +/- 14.51 years). When correlating the number of blood vessels and metalloproteinases with perimatrix thickness, we obtained the following values: pediatric CD31, 7 (4-11); adult CD31, 4 (0-10) (P = 0.044); pediatric cytoplasmatic MMP2, 1 (0-3); adult cytoplasmatic MMP2, 0 (0-1) (P = 0.006); pediatric nuclear MMP2, 0 (0-1); adult nuclear MMP2, 0 (0-1) (P = 0.056); pediatric MMP9, 2 (0-4); adult MMP9, 0 (0-4) (P = 0.049). In conclusion, pediatric cholesteatomas present a more exacerbated inflammatory degree, produce more metalloproteinases, factors that, when combined, could characterize pediatric cholesteatomas as more aggressive than adult cholesteatomas.

Endoscopic injection of filler agents into the esophagogastric junction has been developed to augment the antireflux barrier and decrease gastroesophageal reflux (GER). However, evidence of efficacy is lacking and serious complications have been reported in humans. The aim of this study was to assess whether endoscopic implantation of polymethylmethacrylate augments the antireflux barrier in a porcine model for GER. Large White pigs underwent esophageal manometry, gastric yield pressure (GYP), and gastric yield volume (GYV) measurements and implantation of PMMA in the distal esophagus under general anesthesia. After follow-up of 28 days, esophageal manometry and gastric yield measurements were repeated and animals sacrificed. Implantation of PMMA was performed in 18 animals, and 14 animals survived 28 days. There was a significant increase in GYP (10.7 mmHg versus 8.1 mmHg; p = 0.017) and GYV (997 ml versus 393 ml; p

Chronic otitis media is generally associated with some degree of hearing loss, which is often the patient’s chief complaint. This hearing loss is usually conductive, resulting from tympanic membrane rupture and/or changes in the ossicular chain due to fixation or erosion caused by the chronic inflammatory process. When cholesteatoma or granulation tissue is present in the middle ear cleft, the degree of ossicular destruction is even greater. An issue that has recently gained attention is additional sensorineural hearing loss due to chronic otitis media. While the conductive loss can be minimized through surgery, sensorineural hearing loss constitutes a permanent after effect, attenuated only through the use of a hearing aid. However, a few groups have reported a decrease in sensorineural function in these patients as well. This survey study performed at a referral center evaluates the occurrence of sensorineural hearing loss in ambulatory patients with this disease. We reviewed the files of patients with unilateral chronic otitis media. One hundred and fifty patients met the inclusion criteria: normal otoscopy and normal hearing in the contralateral ear. Main outcome measure: bone-conduction threshold averages were calculated for frequencies of 500, 1,000, 2,000, 3,000 and 4,000 Hz, with comparison between the normal ear and the ear with chronic otitis media. Thresholds were examined separately for each frequency. The bone-conduction threshold averages for the normal side were lower than those for the ear with chronic otitis media. The threshold shift was statistically significant for each frequency (P < 0.0001, Student’s t test). There were differences between the groups when analyzed for age (500 and 1,000 Hz) or the presence of cholesteatoma (1,000 Hz). This study shows that chronic otitis media is associated with a decrease in cochlear function.

This paper introduces a new model for block-based image inpainting in the wavelet domain. The proposed technique separates the inpainting process into two different and important steps, both using the energy of wavelet coefficients. First, the model explores wavelet detail coefficients to estimate the image gradient vector, weighting each vector with the energy of wavelet coefficients. Such information is then used to determine which block belonging to the inpainting region should be filled first. After that, an adapted method for texture synthesis in the wavelet domain is applied in order to successfully fill this block. These two steps are applied successively, until the inpainting region is completely filled. Experimental results indicate that the proposed algorithm can fill large inpainting regions with good visual quality, presenting results comparable to or better than other competitive approaches for image inpainting.

This work describes a model for understanding people motion in video sequences using Voronoi diagrams, focusing on group detection and classification. We use the position of each individual as a site for the Voronoi diagram at each frame, and determine the temporal evolution of some sociological and psychological parameters, such as distance to neighbors and personal spaces. These parameters are used to compute individual characteristics (such as perceived personal space and comfort levels), that are analyzed to detect the formation of groups and their classification as voluntary or involuntary. Experimental results based on videos obtained from real life as well as from a crowd simulator were analyzed and discussed.

Survival of children with acute lymphoblastic leukaemia (ALL) has increased considerably in recent years and data on the spontaneous growth and final height of these children are conflicting. Therefore, we analysed the longitudinal growth and final height in 52 survivors (33 females, 19 males) of childhood ALL. These children were diagnosed and treated in a single institution, all remained in first remission and were submitted to cranial irradiation with either 2400 or 1800 cGy. None of the patients received testicular or spinal irradiation. Median age at diagnosis was 4.2 (range 1.3–9.6) years in the first group (2400 cGy) and 3.9 (0.8–10.5) years in the second (1800 cGy). Standing height was measured at diagnosis, at the end of treatment (median 3.1 years after diagnosis), 6, 12, 24 months after the end of treatment, and finally at the completion of growth. In girls a significant decrease of mean height standard deviation score (SDS) during treatment and a catch up in growth after the end of therapy was followed by a second period of reduced growth. Mean final height SDS was significantly lower than the value at diagnosis in both groups of girls, but only in males treated with 2400 cGy. Mean overall loss in height SDS from diagnosis to final heigth was higher in females (−1.24) than in males (−0.40) (P=0.009). Females 4 years. An unchanged or improved final height was evident in 8 cases, the other 44 cases showed a final height decrease between −0.1 and −2 SDS in 36 and >-2 SDS in 8, 6 of whom were females 4 years. Only females treated at a younger age showed a final height lower than midparental height (−5.7±1.8 cm,P

Sentinel lymph node (SLN) biopsy is currently the method of choice to assess the nodal status of patients with cutaneous melanoma. It has largely replaced elective lymph node dissection, sparing patients with negative SLN the morbidity associated with a complete regional lymphadenectomy. However, experience with the SLN procedure in anal melanoma has been limited to a few reported cases, probably due to the rarity of this tumor. Anorectal melanoma (AM) accounts for 1% of all anorectal malignancies. Most patients are diagnosed with advanced disease and have poor 5-year survival (0–22%). Although surgery is the mainstay of treatment, there appears to be no difference in survival whether wide local excision (LE) or abdominoperineal resection is performed. Locoregional metastases are frequent and may involve both inguinal and pelvic lymph nodes [1]. In this letter, we report a case of AM that had an unexpectedly favorable clinical evolution. Our patient was an 89-year-old diabetic woman presenting with an anal lesion that she first noticed 8 months earlier. It was a non-pigmented nodule, 3 cm in diameter, located at the dentate line. Inguinal palpation was unremarkable. Biopsy of the lesion showed an undifferentiated tumor, but the immunohistochemical analysis was positive for S-100 protein and HMB-45, thus establishing the diagnosis of AM. Staging workup did not detect metastases. Considering the general condition of the patient, treatment by wide local excision of the tumor along with SLN biopsy was proposed. Twelve hours before surgery, Dextran 500 labeled with Technetium-99 m was injected into the parenchyma around the primary tumor. Subsequently, lymphoscintigraphy demonstrated a SLN (hot spot) in the right groin (Fig. 1). On the following day, patent blue dye was injected at the same sites around the tumor. The inguinal area was scanned with a gamma probe, and a 3-cm incision was made over the hot spot. During inguinal dissection, the blue color of the SLN served as a guide to its location. After removal of the SLN, excision of the AM was performed. Histopathology and immunohistochemistry of the surgical specimen confirmed AM with tumor-free resection margins. The SLN was diagnosed as positive for metastatic melanoma. The patient refused any additional treatment but remained free of disease after 52 months of follow-up. Although the SLN procedure has been successfully tested in other anal tumors, the investigation into the SLN in AM is currently limited to 6 cases [1–4]. Long-term survival was not documented in any of them. In our patient, we used the same SLN procedure we had previously investigated in cases of epidermoid carcinoma of the anal canal and rectal adenocarcinomas invading the dentate line [5, 6]. Our technique, which consisted of a combination of blue dye and radio-colloid, was effective in sampling a SLN from the left inguinal area. Moreover, it allowed the detection of metastatic deposits within the SLN, which D. C. Damin (&) M. A. Rosito Division of Coloproctology, Hospital de Clinicas de Porto Alegre (Sala 600) and Department of Surgery, Federal University of Rio Grande do Sul, Rua Ramiro Barcelos 2350, 90035 903 Porto Alegre, RS, Brazil e-mail: damin@terra.com.br

Glioblastoma multiforme (GBM) is a diffuse brain tumor characterized by high infiltration in the brain parenchyma rendering the tumor difficult to eradicate by neurosurgery. Efforts to identify molecular targets involved in the invasive behavior of GBM suggested ion channel inhibition as a promising therapeutic approach. To determine if the Ca 2+ -dependent K + channel KCa3.1 could represent a key element for GBM brain infiltration, human GL-15 cells were xenografted into the brain of SCID mice that were then treated with the specific KCa3.1 blocker TRAM-34 (1-((2-chlorophenyl) (diphenyl)methyl)-1H- pyrazole). After 5 weeks of treatment, immunofluorescence analyses of cerebral slices revealed reduced tumor infiltration and astrogliosis surrounding the tumor, compared with untreated mice. Significant reduction of tumor infiltration was also observed in the brain of mice transplanted with KCa3.1-silenced GL-15 cells, indicating a direct effect of TRAM-34 on GBM-expressed KCa3.1 channels. As KCa3.1 channels are also expressed on microglia, we investigated the effects of TRAM-34 on microglia activation in GL-15 transplanted mice and found a reduction of CD68 staining in treated mice. Similar results were observed in vitro where TRAM-34 reduced both phagocytosis and chemotactic activity of primary microglia exposed to GBM-conditioned medium. Taken together, these results indicate that KCa3.1 activity has an important role in GBM invasiveness in vivo and that its inhibition directly affects glioma cell migration and reduces astrocytosis and microglia activation in response to tumor-released factors. KCa3.1 channel inhibition therefore constitutes a potential novel therapeutic approach to reduce GBM spreading into the surrounding tissue. © 2013 Macmillan Publishers Limited All rights reserved.