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Background: We evaluated a strategy to shorten the time from admission to surgery in patients with proximal femur fractures on chronic antiplatelet therapy. We reported a 12-month follow-up on complications and quality of life (QoL)., Methods: Multicentre, open-label, randomized, parallel clinical trial. Patients were randomized to either early platelet function-guided surgery (experimental group) or delayed surgery (control group). Medical and surgical complications and QoL (EQ-5D-5L questionnaire) were assessed during the hospital stay, and after hospital discharge at 30 days, and 6 and 12 months., Results: From 156 randomized patients, 143 patients underwent surgery. The mean age was 85.5 (7.8) years and 68.0% were female. After hospital discharge, 5.7% of patients had surgical wound complications and 55.9% had medical complications, with 42.7% having serious adverse events. QoL improved significantly after surgery, with the best scores at the six-month follow-up. The overall mortality was 32.2%. There were no differences between early and delayed surgery groups in any assessed outcomes., Conclusion: It seems safe to reduce the time of surgery under neuraxial anaesthesia in patients with hip fractures on chronic antiplatelet therapy by platelet function testing. QoL in particular improves in the first six months after surgery.

Stresses associated with changes in diet or environmental disturbances are common situations that fish encounter during their lifetime. The stability and ease of measuring microRNAs (miRNAs) present in biological fluids make these molecules particularly interesting biomarkers for non-lethal assessment of stress in animals. Rainbow trout were exposed for four weeks to abiotic stress (moderate hypoxia) and/or nutritional stress (a high-carbohydrate/low-protein diet). Blood plasma and epidermal mucus were sampled at the end of the experiment, and miRNAs were assessed using small RNA sequencing. We identified four miRNAs (miR-122-5p, miR-184-3p, miR-192-5p and miR-194a-5p) and three miRNAs (miR-210-3p, miR-153a-3p and miR-218c-5p) that accumulated in response to stress in blood plasma and epidermal mucus, respectively. In particular, the abundance of miR-210-3p, a hypoxamiR in mammals, increased strongly in the epidermal mucus of rainbow trout subjected to moderate hypoxia, and can thus be considered a relevant biomarker of hypoxic stress in trout. We explored the contribution of 22 tissues/organs to the abundance of circulating miRNAs (c-miRNAs) in blood plasma and epidermal mucus influenced by the treatments. Some miRNAs were tissue-specific, while others were distributed among several tissues. Some c-miRNAs (e.g., miR-210-3p, miR184-3p) showed similar variations in both tissues and fluids, while others showed an inverse trend (e.g., miR-122-5p) or no apparent relationship (e.g. miR-192-5p, miR-194a-5p. Overall, these results demonstrate that c-miRNAs can be used as non-lethal biomarkers to study stress in fish. In particular, the upregulation of miR-210-3p in epidermal mucus induced by hypoxia demonstrates the potential of using epidermal mucus as a matrix for identifying non-invasive biomarkers of stress. This study provides information about the tissue sources of c-miRNAs and highlights the potential difficulty in relating variations in miRNA abundance in biological fluids to that in tissues., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Reproductive performances, and the factors affecting them, are of major importance especially for farmed fish in the context of the development of a sustainable aquaculture. Dietary maternal lipids have been identified as a major factor affecting reproductive performances. Nevertheless, the consequences of carbohydrates have been little studied while plant-derived carbohydrates could be increasingly used in broodstock diets. To explore this issue, 2-year-old female trout were fed either a control diet that contains no carbohydrate and a high protein content (65.7%) or a diet formulated with plant-derived carbohydrates containing 32.5% carbohydrate and 42.9% protein ('HC diet') for an entire reproductive cycle. The reproductive performances, the quality of the unfertilized eggs and the development of the progeny were carefully monitored. Although the one year HC nutrition had not impaired female growth nor spawns quality, such nutrition had increased the variability of eggs size within spawns (+ 34.0%). Moreover, the eggs produced had a modified fatty acid profile, including a significant reduction in EPA content (- 22.9%) and a significant increase in the AA/EPA ratio (+ 33.3%). The progeny were impacted by such alterations as their survival rates were significantly reduced. A lower plant-derived carbohydrate inclusion (20%) should be considered in aquafeed for female broodstock in trout., (© 2022. The Author(s).)

Physical enrichment is known to improve living conditions of fish held in farming systems and has been shown to promote behavioral plasticity in captive fish. However, the brain's regulatory-mechanism systems underlying its behavioral effects remain poorly studied. The present study investigated the impact of a three-month exposure to an enriched environment (EE vs. barren environment, BE) on the modulation of brain function in rainbow trout ( Oncorhynchus mykiss ) juveniles. Using high-throughput RT-qPCR, we assessed mRNA genes related to brain function in several areas of the trout brain. These included markers of cerebral activity and plasticity, neurogenesis, synaptogenesis, or selected neurotransmitters pathways (dopamine, glutamate, GABA, and serotonin). Overall, the fish from EE displayed a series of differentially expressed genes (neurotrophic, neurogenesis, and synaptogenesis markers) essentially localized in the telencephalon, which could underpin the beneficial effects of complexifying the environment on fish brain plasticity. In addition, EE significantly affected blood plasma c-miRNA signatures, as revealed by the upregulation of four c-miRNAs (miR-200b/c-3p, miR-203a-3p, miR-205-1a-5p, miR-218a-5p) in fish blood plasma after 185 days of EE exposure. Overall, we concluded that complexifying the environment through the addition of physical structures that stimulate and encourage fish to explore promotes the trout's brain function in farming conditions.

Background: The broodstock diet, and in particular the lipid and fatty acid composition of the diet, is known to play a key role in reproductive efficiency and survival of the progeny in fish. A major problem when replacing both fish meal and fish oil by plant sources is the lack of n-3 long chain polyunsaturated fatty acids, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). To address this problem, we studied the effect of the plant-based diet supplemented with Schizochytrium sp. microalgae, source of DHA, compared to a conventional commercial diet rich in fish meal and fish oil on reproductive performance and egg quality and the consequences on progeny, in female rainbow trout broodstock., Results: The results demonstrated that DHA-rich microalgae supplementation in a plant-based diet allowed for the maintenance of reproductive performance and egg quality comparable to a conventional commercial feed rich in fish meal and fish oil and led to an increased significant fry survival after resorption. Moreover, when females were fed a plant-based diet supplemented with micro-algae, the 4-month-old progenies showed a significant higher growth when they were challenged with a similar diet as broodstock during 1 month. We provide evidence for metabolic programming in which the maternal dietary induced significant protracted effects on lipid metabolism of progeny., Conclusions: The present study demonstrates that supplementation of a plant-based diet with DHA-rich microalgae can be an effective alternative to fish meal and fish oil in rainbow trout broodstock aquafeed., (© 2022. The Author(s).)

The aim of this study was to examine the effect of trial-by-trial corrective feedback in a go-no-go task for children. A sample of 40 preschool students, divided into 4- and 5-year-olds, participated in the study, as well as a group of 20 university students. All the groups performed the task in a counterbalanced design of blocks with and without corrective feedback. Reaction time and accuracy rate were measured as dependent variables. Moreover, reaction time was also analyzed through an ex-Gaussian fit. Children were slightly more accurate and slower under the presence of corrective feedback, suggesting a more conservative pattern. University students were faster, but corrective feedback did not reach the statistical level. Regarding reaction time components, a reduction of the distribution tails, depicted by the τ parameter, was found for both groups under the corrective feedback condition. This suggests that parameterization of reaction time can be considered as a strategy for a more detailed analysis to examine the effect of corrective feedback, even at early ages. In this way, corrective feedback depicted beneficial effects in the τ parameter at early ages, suggesting its use in basic cognitive tasks based on go-no-go but not for older groups.

Background: Circulating miRNAs (c-miRNAs) are found in most, if not all, biological fluids and are becoming well-established non-invasive biomarkers of many human pathologies. However, their features in non-pathological contexts and whether their expression profiles reflect normal life history events have received little attention, especially in non-mammalian species. The aim of the present study was to investigate the potential of c-miRNAs to serve as biomarkers of reproductive and metabolic states in fish., Results: The blood plasma was sampled throughout the reproductive cycle of female rainbow trout subjected to two different feeding regimes that triggered contrasting metabolic states. In addition, ovarian fluid was sampled at ovulation, and all samples were subjected to small RNA-seq analysis, leading to the establishment of a comprehensive miRNA repertoire (i.e., miRNAome) and enabling subsequent comparative analyses to a panel of RNA-seq libraries from a wide variety of tissues and organs. We showed that biological fluid miRNAomes are complex and encompass a high proportion of the overall rainbow trout miRNAome. While sharing a high proportion of common miRNAs, the blood plasma and ovarian fluid miRNAomes exhibited strong fluid-specific signatures. We further revealed that the blood plasma miRNAome significantly changed depending on metabolic and reproductive states. We subsequently identified three evolutionarily conserved muscle-specific miRNAs or myomiRs (miR-1-1/2-3p, miR-133a-1/2-3p, and miR-206-3p) that accumulated in the blood plasma in response to high feeding rates, making these myomiRs strong candidate biomarkers of active myogenesis. We also identified miR-202-5p as a candidate biomarker for reproductive success that could be used to predict ovulation and/or egg quality., Conclusions: Together, these promising results reveal the high potential of c-miRNAs, including evolutionarily conserved myomiRs, as physiologically relevant biomarker candidates and pave the way for the use of c-miRNAs for non-invasive phenotyping in various fish species., (© 2021. The Author(s).)

Vascularized composite allografts contain various tissue components and possess relative antigenicity, eliciting different degrees of alloimmune responses. To investigate the strategies for achieving facial allograft tolerance, we established a mouse hemiface transplant model, including the skin, muscle, mandible, mucosa, and vessels. However, the immunomodulatory effects of the mandible on facial allografts remain unclear. To understand the effects of the mandible on facial allograft survival, we compared the diversities of different facial allograft-elicited alloimmunity between a facial osteomyocutaneous allograft (OMC), including skin, muscle, oral mucosa, and vessels, and especially the mandible, and a myocutaneous allograft (MC) including the skin, muscle, oral mucosa, and vessels, but not the mandible. The different facial allografts of a BALB/c donor were transplanted into a heterotopic neck defect on fully major histocompatibility complex-mismatched C57BL/6 mice. The allogeneic OMC (Allo-OMC) group exhibited significant prolongation of facial allograft survival compared to the allogeneic MC group, both in the presence and absence of FK506 immunosuppressive drugs. With the use of FK506 monotherapy (2 mg/kg) for 21 days, the allo-OMC group, including the mandible, showed prolongation of facial allograft survival of up to 65 days, whereas the myocutaneous allograft, without the mandible, only survived for 34 days. The Allo-OMC group also displayed decreased lymphocyte infiltration into the facial allograft. Both groups showed similar percentages of B cells, T cells, natural killer cells, macrophages, and dendritic cells in the blood, spleen, and lymph nodes. However, a decrease in pro-inflammatory T helper 1 cells and an increase in anti-inflammatory regulatory T cells were observed in the blood and lymph nodes of the Allo-OMC group. Significantly increased percentages of donor immune cells were also observed in three lymphoid organs of the Allo-OMC group, suggesting mixed chimerism induction. These results indicated that the mandible has the potential to induce anti-inflammatory effects and mixed chimerism for prolonging facial allograft survival. The immunomodulatory understanding of the mandible could contribute to reducing the use of immunosuppressive regimens in clinical face allotransplantation including the mandible.

Objectives: Postpyloric enteral feeding tubes (PPTs) are often placed endoscopically. This carries cost and capacity implications for hospitals with additional strain on endoscopy units during the SARS-CoV-2 pandemic. The Kangaroo Feeding Tube with IRIS Technology (IRIS) uses optical visualization to guide bedside placement, obviating the need for endoscopy. We describe a case series of bedside postpyloric enteral feeding tube placement using the IRIS tube., Methods: This was a prospective, single-center case series over 12 mo. Conscious and sedated adult participants were included. Exclusion criteria were altered anatomy and need for endoscopy for other indications. IRIS placement was confirmed by contrast radiograph., Results: Twenty attempts were made in 19 participants (13 women). The primary indication was intolerance of gastric feeding. The overall success rate was 75%. In sedated participants, 5 (83%) of 6 tubes were successful in 5 participants. In conscious participants, 10 (71%) of 14 tubes were successful in 14 participants. Placement failure in conscious participants was due to intolerance of the camera tip during nasal passage. The median procedure time was 13.5 min. In all cases, correct position as deemed by the operator was confirmed with contrast radiograph. No complications were observed., Conclusions: To our knowledge, this is the largest single series of bedside postpyloric enteral feeding tube placement using the IRIS tube to date. The success rate and safety profile reported here, together with the potential benefits (reduced feeding delays, costs, and need for endoscopy) suggest that further, large-scale studies are warranted., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Assessing female fish reproductive success requires a thorough evaluation of egg characteristics, including egg number, size, and variability as well as egg developmental potential through the monitoring of embryo survival after fertilization. While embryonic success relies, at least in part, on paternal contribution, some parameters are strictly related to egg characteristics, one of the main ones being the viability of the egg when released into the water at spawning. It is however not necessarily possible, at least in salmonid fish that lay nontransparent eggs, to separate the different causes of egg/embryo failure. In this context, our aim was (i) to develop a simple and rapid system to capture images of rainbow trout eggs combined with computerized processing of these images to perform a fully automatic individual characterization of egg features including number and size (ii) to estimate unfertilized egg viability through the monitoring of the percentage of eggs that will not survive to water hydration. To evaluate the VisEgg system, unfertilized eggs (approximatively 400 eggs per batch) originating from 105 different females were hydrated in water. After 24 h, a picture of the eggs was obtained using a dedicated shooting system consisting of a light source and a digital single-lens reflex (SLR) camera. An image processing algorithm was developed to allow the automatic detection and separation of the eggs and to perform automatic measurements of egg number and individual egg size. The presence of white egg was used as an indirect measure of egg integrity, the "whitening" being the result of water entry into the egg through the vitelline membrane. These white eggs were therefore considered nonviable, as a result of their lack of physical integrity. Fertilization assays were performed in parallel using a subsample of the same egg batch. Embryonic development was monitored and hatching rate was calculated. A significant correlation between white egg percentage after hydration and hatching rate was observed (Spearman coefficient = -0.557, p < 0.001), in consistency with the fact that nonviable egg will not allow successful embryonic development. In contrast, the percentage of eggs that do not successfully hatch includes egg/embryo failures of different nature including reduced egg viability. Using the VisEgg, we were able to quantify the lack of viability of the eggs separately from the different other events that may occur during fertilization and incubation. the VisEgg is a convenient and reliable tool to obtain individual measures on trout eggs. It can be used to assess not only egg size and egg number but also unfertilized egg viability before fertilization.

Land-use alteration and climate seasonality have profound effects on bee species diversity by influencing the availability of nesting and floral resources. Here, using twelve sites embedded in an agriculture-forest mosaic in the tropical highlands of Guatemala, we investigated the relative effects of climate seasonality and landscape heterogeneity on bee and floral-resource community structure and on their mutualistic network architecture. We found that climate seasonality affected bee diversity, which was higher in the wet season and associated positively with the availability of floral resources across both seasons. Bee community composition also differed between seasons and it was mainly driven by floral-resource richness and the proportion of agricultural, semi-natural and forest cover. In addition to the effects on bee diversity, climate seasonality also affected flower-bee visitation networks. We documented higher relative (null model corrected) nestedness in the dry season compared to the wet season. Niche partitioning as a result of competition for scarce resources in the dry season could be the process driving the differences in the network structure between seasons. Furthermore, relative nestedness was consistently smaller than zero, and relative modularity and specialization were consistently larger than zero in both seasons, suggesting the existence of isolated groups of interacting partners in all our flower-bee visitation networks. Our results highlight the effect of climatic seasonality and the importance of preserving local floral resources and natural heterogeneous habitats for the conservation of bee communities and their pollination services in tropical highlands.

Deciphering mechanisms of oocyte development in the fish ovary still remain challenging, and a comprehensive overview of this process at the level of the organ is still needed. The recent development of optical tissue clearing methods has tremendously boosted the three-dimensional (3D) imaging of large size biological samples that are naturally opaque. However, no attempt of clearing on fish ovary that accumulates extremely high concentration of lipids within oocytes has been reported to date. To face with this ovarian-specific challenge, we combined two existing clearing methods, the nontoxic solvent-based ethyl cinnamate (ECi) method for efficient clearing and the Clear Unobstructed Brain Imaging Cocktails and Computational (CUBIC) method to enhance lipid removal and reduce nonspecific staining. The methyl green fluorescent dye was used to stain nuclei and delineate the follicular structures that include oocytes. Using this procedure (named CUBIC-ECi [C-ECi]), ovaries of both medaka and trout could be imaged in 3D and follicles analyzed. To our knowledge, this is the first procedure elaborated for clearing and imaging fish ovary in 3D. The C-ECi method thus provides an interesting tool for getting precise quantitative data on follicular content in fish ovary and promises to be useful for further developmental and morphological studies., (© The Author(s) 2020. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The auto-fluorescent coenzymes reduced nicotinamide dinucleotide (NADH) and oxidized flavin adenine dinucleotide (FAD) allow label-free detection of cellular metabolism. The optical redox ratio, which is traditionally computed as the ratio of NADH and FAD intensities, allows quantification of cell redox state. In addition to multiple formulations of the optical redox ratio from NADH and FAD intensity measurements, a fluorescence lifetime redox ratio (FLIRR) based on the fractions of protein-bound NADH and FAD was developed to overcome the limitations of experimental factors that influence fluorescence intensity measurements. In this paper, we compare fluorescence-intensity computations of the optical redox ratio with the fluorescence lifetime redox ratio for quiescent and activated T cells. Fluorescence lifetime images of NAD(P)H and FAD of T cells were acquired with a two-photon fluorescence lifetime microscope. Metabolic perturbation experiments, including inhibition of glycolysis, oxidative phosphorylation, glutaminolysis, and fatty acid synthesis revealed differences between the intensity and lifetime redox ratios. Statistical analysis reveals that the FLIRR has a lower standard deviation and skewness (two-tail T-test, P value = 0.05) than the intensity redox ratio. Correlation analysis revealed a weak relationship between FLIRR and intensity redox ratio for individual cells, with a stronger correlation identified for activated T cells (Linear regression, R-value = 0.450) than quiescent T cells (R-value = 0.172). Altogether, the results demonstrate that while both the fluorescence lifetime and intensity redox ratios resolve metabolic perturbations in T cells, the endpoints are influenced by different metabolic processes., Competing Interests: The authors declare no conflicts of interest., (© 2020 Optical Society of America under the terms of the OSA Open Access Publishing Agreement.)

Tau protein accumulation is a common denominator of major dementias, but this process is inhomogeneous, even when triggered by the same germline mutation. We considered stochastic misfolding of human tau conformers followed by templated conversion of native monomers as an underlying mechanism and derived sensitive conformational assays to test this concept. Assessments of brains from aged TgTau P301L transgenic mice revealed a prodromal state and three distinct signatures for misfolded tau. Frontotemporal lobar degeneration (FTLD)-MAPT-P301L patients with different clinical phenotypes also displayed three signatures, two resembling those found in TgTau P301L mice. As physicochemical and cell bioassays confirmed diverse tau strains in the mouse and human brain series, we conclude that evolution of diverse tau conformers is intrinsic to the pathogenesis of this uni-allelic form of tauopathy. In turn, effective therapeutic interventions in FTLD will need to address evolving repertoires of misfolded tau species rather than singular, static molecular targets.

Introduction: While no consensus on the optimal salvage treatment exists, only 3% of these patients will get salvage radical prostatectomies due to the assumed technical challenges of this procedure., Objectives: Our goal is to analyze the perioperative, oncologic and functional outcomes of patients undergoing salvage robotic-assisted radical prostatectomy (sRARP) after primary treatment failure., Materials and Methods: Data were prospectively collected and retrospectively reviewed from a combined database of more than 14,800 patients who had undergone RARP. We identified 96 patients who underwent sRARP after RT or ablative techniques. Primary cancer characteristics, surgical data, pathology results, perioperative complications, oncologic and functional outcomes were analyzed., Results: Sixty-eight patients (70.8%) received some source of RT as a primary treatment. The remaining 28 patients: 18 (18.75%) received cryotherapy, seven (7.92%) HIFU, one electroporation, one microwave and one Tookad. complication was seen in 25 (26%) patients (21 minor and 4 major complications). Anastomotic leak was the most common complication, found in 14 (14.6%) of the cases. No rectal injuries occurred. Fourteen (15%) patients had a biochemical failure after a median follow-up of 14 (IQR 5-24) months. Fifty-five (57.3%) of them self-reported to be pad-free at 12 months. Seventeen (55%) of 31 pre-operative potent patients (SHIM score > 21), were potent with or without the use of PDE5i at 12 months., Conclusions: sRARP is a feasible alternative for PCa recurrence. Technically the procedure is challenging and should be performed by experienced PCa surgeons. Major complications are uncommon. Continence and potency recovery is possible, but at lower rates than for non-salvage patients.

Background: In immunologic research, mice have advantages over other animals, such as low costs, easy handling, suitable life cycle, and adequate laboratory resources. However, vascularized composite allotransplantation surgery using mice is not popular, partly because of technical difficulties and high mortality rates. The authors' goal was to demonstrate a face transplantation model in mice that includes skin, mandible, and oral mucosa., Methods: The authors developed a new syngeneic face transplantation model composed of skin, mandible, teeth, and oral mucosa in C57BL/6 mice. The following assessment included measuring the length of the right incisor on the transplanted mandibles, computed tomographic scan in one mouse for mandibular structure evaluation, and histologic examination of different tissue samples in another mouse for viability evaluation., Results: The authors performed five consecutive transplantations. The donor vessels were the common carotid artery (approximately equal to 0.4 mm) and the anterior facial vein (approximately equal to 0.2 mm), and the recipients were the common carotid artery and the posterior facial vein (approximately equal to 0.4 mm). The mean operative time was 80 minutes for the donor and 123 minutes for the recipient. There were neither flap failures nor animal deaths. The follow-up was 6 months. The right incisor of the transplant grew at different rates in all cases. Histologic samples showed viability in all tissues, including mandibular bone marrow. Computed tomography demonstrated normal structure of the transplanted bone., Conclusion: The authors' syngeneic partial face transplantation model in mice, which included skin, oral mucosa, and mandible with teeth, should be useful for future face allotransplantation research, as the myriad of tissues it provides, of different immunomodulatory functions, is similar to that in the clinical scenario.

Background: Live surgery events (LSEs) have become one of the most attended activities at surgical meetings and provide a unique opportunity for the audience to observe the decision-making process used by skilled and experienced surgeons in real time. However, there is an ongoing discussion on whether patients treated during LSE are at higher risk of complications., Objective: To examine LSE outcomes for robot-assisted radical prostatectomy (RARP) and establish patient safety and efficacy., Design, Setting, and Participants: From January 2008 to April 2016, >9000 patients underwent RARP at our institution, performed by a single surgeon. From this group, 36 patients underwent live RARP surgery (LS group) transmitted via video link from our institution to an external congress. A control group was obtained from our database to compare outcomes between the LS group and patients undergoing RARP under regular circumstances. The data were prospectively collected in a customized database and retrospectively analyzed., Intervention: All patients underwent RARP performed by a single surgeon at our institution., Outcome Measurements and Statistical Analysis: Postoperative outcomes were compared between the LS (n=36) and the control (n=108) groups using Student's t test and analysis of variance for continuous variables, and a two-tailed Fisher's exact test for categorical variables. Statistical significance was set at p<0.05., Results and Limitations: There were no significant differences in baseline characteristics (age, body mass index, comorbidities, preoperative Gleason score, Sexual Health Inventory for Men score and American Urological Association symptom score) between the groups. The median console time was shorter for the LS group (73min, interquartile range [IQR] 70-79) than for the control group (78min, IQR 75-87; p=0.0371). No major complications were reported in either group, and only four minor complications were observed in the control group (p=0.2415). After median follow-up of 31 mo (IQR 18-50), only one patient (2.77%) in the LS group experienced biochemical recurrence, compared to four (3.71%) in the control group (p=0.7927). There was no significant difference in continence rates between the LS and control groups (97.22% vs 93.52%; p=0.7768). No differences in potency rate were evident by the end of the follow-up period (LS 69.44%, control group 70.37%; p=0.8432). The retrospective nature, the lack of randomization, and the single-institution experience are limitations of the study., Conclusions: In this series of live transmitted RARPs, perioperative results (oncological and functional outcomes and complications) were similar to those found in daily practice. After careful patient selection, LSEs are safe with minimal patient morbidity in the hands of an experienced surgeon working with a familiar surgical team. Further evaluation of the results from other surgeons at other centers is necessary., Patient Summary: We investigated the safety of surgeries broadcast live from our institution. We found that outcomes were similar to those for patients undergoing surgery under regular circumstances in terms of the rate of complications and oncological and functional outcomes. We conclude that live transmitted surgery is safe in well-selected patients in the hands of an experienced surgeon., (Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

The aetiology of behavioural and psychological symptoms of dementia (BPSD) is defined by a diversity of factors, and recent studies suggest that premorbid personality could be a risk factor for BPSD. This study aimed to review studies on the relationship between premorbid personality and BPSD. Studies were identified using PsycInfo, MedLine, and PubMed. The searches combined terms for premorbid personality, dementia and BPSD. Ten studies have been included in this review. Eight out of ten studies show a relationship between premorbid personality and BPSD. Neuroticism is associated with behavioural disturbances and anxiety. Extraversion is associated with wandering. Low agreeableness is associated with affective disturbance and aggression-related behaviours and high agreeableness is associated with wandering. The studies found no congruent results for openness and conscientiousness. In conclusion, premorbid personality may increase the risk of developing BPSD during the course of the disease. Even so, the relationship between personality and BPSD is complex due to multifactorial aetiology., (Copyright © 2018 SEGG. Publicado por Elsevier España, S.L.U. All rights reserved.)

Objectives: The fact that more and more people suffer from dementia makes it very important to know the different risk factors to prevent their appearance. The objective of this article is to study personality disorder as a possible risk factor for the onset of an insane process, and to relate personality disorders of Cluster B and dementia., Methodology: A systematic review and meta-analysis was carried out with scientific literature published up to 2015., Results: Twelve of the articles that we found met the specified criteria of selection and quality and study the relationship between a personality disorder and the emergence of a dementia. Although with the studies made so far it can't be concluded that the first one is a risk factor for the second one, it has been noted, thanks to neuroimaging techniques, that patients with Cluster B personality disorders develop alterations in brain structures (in the prefrontal, temporal and parietal cortex, as well as an alteration in the NAA levels and the grey matter levels) and which are also involved in a demented process., Conclusions: Definitely, the patients with medical record of the borderline or narcissistic personality disorder present more alterations in the brain structures mentioned, such that presenting these types of personality disorders could increase the risk of developing dementia in the future.

Objective: To show the feasibility, oncological and functional outcomes of neurovascular bundle (NVB) preservation during salvage robot-assisted radical prostatectomy (RARP)., Patients and Methods: In the present institutional review board-approved retrospective analysis, between January 2008 and March 2016, 80 patients underwent salvage RARP, performed by a single surgeon (V.P), because of local recurrence after primary treatment. These patients were categorized into two groups depending on the degree of nerve-sparing (NS) performed: a good-NS group (≥50% of NVB preservation) and a poor-NS group (<50% of NVB preservation). A standard transperitoneal six-port technique, using the DaVinci Surgical System (Intuitive Surgical, Sunnyvale, CA, USA), was performed, and either an anterograde or a retrograde approach was used for NVB preservation. Validated questionnaires were used preoperatively (Sexual Health Inventory for Men [SHIM] and American Urological Association scores). Potency after salvage RARP was defined as the ability to achieve a successful erection with penetration >50% of the time, while full continence after salvage RARPwas defined as 0 pads used. The Kaplan-Meier method was used for survival and predictive estimations, and regression models were used to identify the predictors of potency, continence and biochemical failure (BCF)., Results: The potency rate at 12 months was higher in the good-NS group (25.6% vs 4.3%; P = 0.036) regardless of previous SHIM score, and good NS tended to be predictive of potency after salvage RARP (P = 0.065). The full continence rate at 12 months and BCF rate were similar in the two groups, and non-radiation primary treatment was the only predictor of continence at 12 months after salvage RARP (P = 0.033)., Conclusions: Our data support the feasibility and safety of NVB preservation for salvage RARP conducted in select patients in a high-volume institution and the subsequent better recovery of adequate erections for intercourse., (© 2018 The Authors BJU International © 2018 BJU International Published by John Wiley & Sons Ltd.)

Using enteroscopes with therapeutic capacity to explore the small intestine entails certain limitations, including long exploration times, patient discomfort, the need for sedation, a high percentage of incomplete explorations and a long learning curve. This article describes the advances and setbacks encountered in designing the new Endoworm enteroscopy system, a semi-autonomous device consisting of a control unit and three cavities that inflate and deflate in such a way that the bowel retracts over the endoscope. The system can be adapted to any commercial enteroscope. Endoworm was tested in different intestine models: a polymethyl methacrylate rigid tube, an in vitro polyester urethane model, an ex vivo pig model and an in vivo animal model. The general behavior of the prototype was evaluated by experienced medical personnel. The mean distance covered through the lumen was measured in each cycle. The system was found to have excellent performance in the rigid tube and in the in vitro model. The ex vivo tests showed that the behavior depended largely on the mechanical properties of the lumen, while the in vivo experiments suggest that the device will require further modifications to improve its performance.

This work presents a systematic approach to study the conservation of genes between fruit flies and mammals. We have listed 971 Drosophila genes involved in female reproduction at the ovarian level and systematically looked for orthologs in the Ciona, zebrafish, coelacanth, lizard, chicken, and mouse. Depending on the species, the percentage of these Drosophila genes with at least one ortholog varies between 69% and 78%. In comparison, only 42% of all the Drosophila genes have an ortholog in the mouse genome (P < 0.0001), suggesting a dramatically higher evolutionary conservation of ovarian genes. The 177 Drosophila genes that have no ortholog in mice and other vertebrates correspond to genes that are involved in mechanisms of oogenesis that are specific to the fruit fly or the insects. Among 759 genes with at least one ortholog in the zebrafish, 73 have an expression enriched in the ovary in this species (RNA-seq data). Among 760 genes that have at least one ortholog in the mouse; 76 and 11 orthologs are reported to be preferentially and exclusively expressed in the mouse ovary, respectively (based on the UniGene expressed sequence tag database). Several of them are already known to play a key role in murine oogenesis and/or to be enriched in the mouse/zebrafish oocyte, whereas others have remained unreported. We have investigated, by RNA-seq and real-time quantitative PCR, the exclusive ovarian expression of 10 genes in fish and mammals. Overall, we have found several novel candidates potentially involved in mammalian oogenesis by an evolutionary approach and using the fruit fly as an animal model.

The objective of this study is to determine if the use of dehydrated human amnion/chorion membrane (dHACM) allograft wrapped around the NVB during a robotic-assisted radical prostatectomy (RARP) accelerates the return to potency. 940 patients with preoperative SHIM >20 underwent RARP with some degree of bilateral NS. Of these, 235 patients underwent RARP, with bilateral placement of dHACM graft around the NVBs. They were matched in a 1:3 proportion with a similar group of patients (n = 705) who did not receive the allograft (control group or group 2). Minimum follow-up was 12 months. Postoperative outcomes were analyzed between propensity-matched dHACM graft (group 1) and non-graft groups (group 2). Kaplan-Meier survival curves were compared across techniques using the log-rank test. There were no significant demographic differences between the two groups. Potency was defined as the ability to achieve and maintain satisfactory erections firm enough for sexual intercourse, with or without the use of PDE-5 inhibitors. The mean time to potency was significantly lower in group 1 (2.37 months) versus group 2 (3.94 months) (p < 0.0001). The potency recovery rates were superior for group 1 at all early time points measured except at 12 months. The time to potency was significantly shorter in the dHACM group with full NS, 2.19 ± 1.84 versus 2.78 ± 2.70 mo. in the non-dHACM with full NS (p = 0.029). In the dHACM group with partial NS, the mean time to potency was 3.05 ± 2.32 versus 3.92 ± 3.42 mo. in the non-dHACM with partial NS (p = 0.021). Patients who received the dHACM wrap around the NVB after RARP accelerates the return to potency when compared to a similar control group without the use of the allograft. We also demonstrated that this faster return to potency occurs regardless of the degree of the NS preservation. Younger patients (<55 years of age) had the highest overall advantage if they received the graft. Our results indicate that dHACM placement at the site of the prostatic NVB does not increase the risk of BCR after RARP, neither in the presence of PSM, extra-prostatic disease (≥pT3) nor high Gleason score (Gleason ≥8).

Robotic radical prostatectomy (RARP) is well established as a safe and effective treatment for prostate cancer. According to published studies, patients undergoing RARP are at increased risk of being diagnosed with an inguinal hernia after RARP and are four times more likely to have an inguinal hernia repair (IHR) following RARP. Several studies have demonstrated the effectiveness and safety of IHR during RARP. Overall, it has been observed that IHR adds on average, 12-15 min in total surgical time and there were no significant differences between RARP with or without IHR with respect to postoperative complications. This study analyzes a large series of patients undergoing RARP (1100) and compares them to a group that underwent RARP with IHR (39). Between December 2008 and January 2015, 1139 patients underwent RARP at Florida Hospital in Celebration, FL. Of the total patients, 39 underwent concomitant IHR. All procedures were performed by the same surgeons (urologist and general surgeon), using the same techniques of RARP and TAPP inguinal hernia repair. After 30 days, the differences were evaluated between groups regarding surgical time, EBL and postoperative complications. The average age of patients undergoing the procedure was 61.65 years. The mean procedure time was approximately 120 min (min), with an additional period of 68 min for IHR (mean = 188; p = 0.0001). There was a significant difference in BMI between the groups, 28.3 kg/m 2 for patients undergoing RARP and 26.8 kg/m 2 for those who underwent RARP and IHR (p = 0.028). The EBL averaged 110.87 mL, with no significant difference between groups (p = 0371). There was no significant association between clinical stage of the patient and the type of procedure performed (p = 12:35). There was no significant difference in the presence of comorbidities and the operation preformed. There were 61 events recorded postoperatively, 57 (5.2%) among patients who underwent only RARP and 4 (10.26%) among those who had both. Taken together, the small amounts of complications in both groups prevent statistical significance. This study compared two groups of patients undergoing RARP: those with IHR and those without. Our study demonstrated an increase in surgical time; however, there was no increase in postoperative complications. From the data presented, we suggest that the performance of both procedures concomitantly is feasible and safe.

Traumatic peripheral nerve neurotmesis occurs frequently and functional recovery is often slow and impaired. Induced pluripotent stem cells (iPSCs) have shown much promise in recent years due to its regenerative properties similar to that of embryonic stem cells. However, the potential of iPSCs in promoting the functional recovery of a transected peripheral nerve is largely unknown. This study is the first to investigate in vivo effects of episomal iPSCs (EiPSCs) on peripheral nerve regeneration in a murine sciatic nerve transection model. Episomal iPSCs refer to iPSCs that are generated via Oct3/4-Klf4-Sox2 plasmid reprogramming instead of the conventional viral insertion techniques. It represents a relatively safer form of iPSC production without permanent transgene integration which may raise questions regarding risks of genomic mutation. A minimal number of EiPSCs were added directly to the transected nerve. Functional recovery of the EiPSC group was significantly improved compared to the negative control group when assessed via serial five-toe spread measurement and gait analysis of ankle angles. EiPSC promotion of nerve regeneration was also evident on stereographic analysis of axon density, myelin thickness, and axonal cross-sectional surface area. Most importantly, the results observed in EiPSCs are similar to that of the embryonic stem cell group. A roughly ten-fold increase in neurotrophin-3 levels was seen in EiPSCs which could have contributed to peripheral nerve regeneration and recovery. No abnormal masses or adverse effects were noted with EiPSC administration after one year of follow-up. We have hence shown that functional recovery of the transected peripheral nerve can be improved with the use of EiPSC therapy, which holds promise for the future of nerve regeneration., Competing Interests: The authors have declared that no competing interests exist.

Background: Biofloc technology (BFT), a rearing method with little or no water exchange, is gaining popularity in aquaculture. In the water column, such systems develop conglomerates of microbes, algae and protozoa, together with detritus and dead organic particles. The intensive microbial community presents in these systems can be used as a pond water quality treatment system, and the microbial protein can serve as a feed additive. The current problem with BFT is the difficulty of controlling its bacterial community composition for both optimal water quality and optimal shrimp health. The main objective of the present study was to investigate microbial diversity of samples obtained from different culture environments (Biofloc technology and clear seawater) as well as from the intestines of shrimp reared in both environments through high-throughput sequencing technology., Results: Analyses of the bacterial community identified in water from BFT and "clear seawater" (CW) systems (control) containing the shrimp Litopenaeus stylirostris revealed large differences in the frequency distribution of operational taxonomic units (OTUs). Four out of the five most dominant bacterial communities were different in both culture methods. Bacteria found in great abundance in BFT have two principal characteristics: the need for an organic substrate or nitrogen sources to grow and the capacity to attach to surfaces and co-aggregate. A correlation was found between bacteria groups and physicochemical and biological parameters measured in rearing tanks. Moreover, rearing-water bacterial communities influenced the microbiota of shrimp. Indeed, the biofloc environment modified the shrimp intestine microbiota, as the low level (27 %) of similarity between intestinal bacterial communities from the two treatments., Conclusion: This study provides the first information describing the complex biofloc microbial community, which can help to understand the environment-microbiota-host relationship in this rearing system.

This study compares the antioxidant and antimicrobial transcriptional expression of blue shrimps reared according to two different systems, BioFloc Technology (BFT) and Clear sea Water (CW) and their differential responses when facing an experimental sublethal hydrogen peroxide stress. After 30 days of rearing, juvenile shrimps were exposed to H2O2 stress at a concentration of 30 ppm during 6 h. The oxidative stress caused by H2O2 was examined in the digestive glands of the shrimp, in which antioxidant enzyme (AOE) and antimicrobial peptide (AMP) gene expression were analysed by quantitative real-time PCR. Results showed that rearing conditions did not affect the expression of genes encoding AOEs or AMPs. However, H2O2 stress induced a differential response in expression between shrimps from the two rearing treatments (BFT and CW). Comparative analysis of the expression profiles indicates that catalase transcripts were significantly upregulated by H2O2 stress for BFT shrimps while no change was observed for CW shrimps. In contrast, H2O2 caused down-regulation of superoxide dismutase and glutathione transferase transcripts and of the three AMP transcripts studied (penaeidin 2 and 3, and crustin) for CW shrimps, while no effect was observed on BFT shrimp transcript levels. These results suggested that BFT shrimps maintained antioxidant and AMP responses after stress and therefore can effectively protect their cells against oxidative stress, while CW shrimp immune competence seems to decrease after stress., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Miniaturization of the steam engine to the microscale is hampered by severe technical challenges. Microscale mechanical motion is typically actuated with other mechanisms ranging from electrostatic interaction, thermal expansion, and piezoelectricity to more exotic types including shape memory, electrochemical reaction, and thermal responsivity of polymers. These mechanisms typically offer either large-amplitude or high-speed actuation, but not both. In this work we demonstrate the working principle of a microscale solid engine (μSE) based on the phase transition of VO2 at 68 °C with large transformation strain (up to 2%), analogous to the steam engine invoking large volume change in a liquid-vapor phase transition. Compared to polycrystal thin films, single-crystal VO2 nanobeam-based bimorphs deliver higher performance of actuation both with high amplitude (greater than bimorph length) and at high speed (greater than 4 kHz in air and greater than 60 Hz in water). The energy efficiency of the devices is calculated to be equivalent to thermoelectrics with figure of merit ZT = 2 at the working temperatures, and much higher than other bimorph actuators. The bimorph μSE can be easily scaled down to the nanoscale, and operates with high stability in near-room-temperature, ambient, or aqueous conditions. On the basis of the μSE, we demonstrate a macroscopic smart composite of VO2 bimorphs embedded in a polymer, producing high-amplitude actuation at the millimeter scale.

As part of our recent effort to attach well-defined molecular photocatalysts to solid-state surfaces, this present study investigates adsorption and photochemical properties of a tricarbonyl rhenium(I) compound, Re(bpy)(CO)3Cl (bpy = 2,2'-bipyridine), in hierarchical mesoporous ZSM-5. The molecular Re(I) catalyst, a Ru(bpy)3(2+) photosensitizer, and an amine-based electron donor were coadsorbed in the mesopores of the hierarchical ZSM-5 through simple liquid-phase adsorption. The functionalized ZSM-5 was then characterized with infrared and UV-visible spectroscopies and was tested in CO2 reduction photocatalysis at the gas-surface interface. In the mesoporous ZSM-5, CO2 molecules were adsorbed on the amine electron-donor molecules as bicarbonate, which would release CO2 upon light irradiation to react with the Re(I) catalyst. The formation of important reaction intermediates, particularly a Re-carboxylato species, was revealed with in situ Fourier transform infrared spectroscopy in combination with isotopic labeling. The experimental results indicate that hierarchical mesoporous zeolites are promising host materials for molecular photocatalysts and that zeolite mesopores are potential "reaction vessels" for CO2 reduction photocatalysis at the gas-solid interface.

We test for two critical phenomena in Amazonian ecosystems: self-organized criticality (SOC) and critical transitions. SOC is often presented in the complex systems literature as a general explanation for scale invariance in nature. In particular, this mechanism is claimed to underlie the macroscopic structure and dynamics of terrestrial ecosystems. These would be inextricably linked to the action of fire, which is conceived as an endogenous ecological process. We show that Amazonian savanna fires display the scale-invariant features characteristic of SOC but do not display SOC. The same is true in Amazonian rainforests subject to moderate drought. These findings prove that there are other causes of scale invariance in ecosystems. In contrast, we do find evidence of a critical transition to a megafire regime under extreme drought in rainforests; this phenomenon is likely to determine the time scale of a possible loss of Amazonian rainforest caused by climate change.

Introduction and Objectives: A study is made of the clinical repercussions of occult metastases-micrometastases (MMs+)-or isolated tumour cells (ITCs+) in the lymph nodes of patients with stage IIA and IIB colon adenocarcinoma initially considered as corresponding to N0., Material and Methods: A retrospective study of 39 patients with stage IIA and IIB (T3-T4 N0 M0) colon adenocarcinoma, subjected to similar surgical and adjuvant chemotherapy treatment, with long and careful follow-up (minimum: 5 years, mean: 81.7 months) was performed on their previously resected lymph nodes, with the aid of new histological and immunohistochemical (cytokeratin) sections, in order to detect MMs or ITCs. Disease-free survival (DFS) and global survival (GS) in the two groups (patients with MMs+ or ITCs+ vs. patients without MMs or ITCs) were compared at 5 years based on the corresponding Kaplan-Meier survival curves, with the Breslow test., Results: A total of 382 lymph nodes from the 39 patients (mean: 9.8; standard deviation: 6.09) were revised. MMs+ were detected in 2 cases and ITCs+ in 2 more cases on the Cytokeratin study. GS of the whole series at 5 years was 89.74% (35 patients alive) with a DFS at 5 years of 79.49% (31 patients free of disease), but the 2 cases with MMs+ were dead at 5 years, with high statistical differences between both groups (MMs+/MMs-) (p<0.0001). When comparing the group of MMs+/ITCs+ patients and the group of MM-/ITCs- patients, the DFS and GS times at 5 years were higher in the MMs-/ITCs- group (p=0.0692 and p=0.006 respectively)., Conclusions: Although the incidence of MMs+ or ITCs+ in the examined lymph nodes was low, the presence of MMs is related to a dramatic reduction in GS and DFS at 5 years. We encourage a detailed histological study of lymph nodes resected in patients with deep penetrating colon tumours in order to assure a pN0 status.

Sphingosine kinase has been recognized as an essential signaling molecule that mediates the intracellular conversion of sphingosine to sphingosine-1-phosphate. In mast cells, induction of sphingosine kinase and generation of sphingosine-1-phosphate have been linked to the initial rise in Ca(2+), released from internal stores, and to degranulation. These events either precede or are concomitant with the activation of phospholipase C-gamma and the generation of inositol trisphosphate. Here we show that sphingosine kinase type 1 (SPHK1) interacts directly with the tyrosine kinase Lyn and that this interaction leads to the recruitment of this lipid kinase to the high-affinity receptor for immunoglobulin E (FcepsilonRI). The interaction of SPHK1 with Lyn caused enhanced lipid and tyrosine kinase activity. After FcepsilonRI triggering, enhanced sphingosine kinase activity was associated with FcepsilonRI in sphingolipid-enriched rafts of mast cells. Bone marrow-derived mast cells from Lyn(-/)(-) mice, compared to syngeneic wild-type cells, were defective in the initial induction of SPHK1 activity, and the defect was overcome by retroviral Lyn expression. These findings position the activation of SPHK1 as an FcepsilonRI proximal event.

IgE plus antigen-stimulated mast cells degranulate, synthesize leukotrienes and secrete cytokines. According to the coalescence model this process is initiated in specific membrane compartments termed rafts. There, enhanced levels of glycosphingolipids and cholesterol stabilize the interaction of FcepsilonRI and Lyn, and thus facilitate the first steps of signal transduction. Enforced changes in raft architecture by cholesterol deprivation and exogenous application of glycosphingolipids influence these early events by loss of tyrosine kinase activity or receptor-independent signal initiation respectively. Here we show that exogenously added cholesterol accumulates in rafts and activates mast cells. An investigation of the signaling events reveals that in contrast to IgE plus antigen-mediated stimulation, cholesterol triggers p38 mitogen-activated protein kinase and preferentially induces expression of FosB. Consequently, a comparative large-scale microarray analysis demonstrates that a number of IgE plus antigen-induced immediate early genes (peak expression at 30 min after induction) are repressed by cholesterol. These changes further translate into altered expression levels and time kinetics of a number of early genes (peak expression at 2 h after stimulation). As the most prominent example for cholesterol-dependent genes, we identified PAI1 (plasminogen activator inhibitor 1), a protein regarded as a risk factor for atherosclerosis.

Growing skull fractures (GSF) are rare complications of head injury (HI) in childhood. This entity consists of a skull fracture with an underlying dural tear that courses with a progressive enlargement of the fracture to produce a cranial defect. The pathophysiology and some aspects of its management are still controversial. In this review we present 12 patients diagnosedd and treated for a GSF at our institution between 1980 and 2002. 11 patients were under the age of 3 years and one patient was 5 years old at the moment of HI. The most common cause of injury was a fall from height. In the initial plain x-rayfilms, 11 patients showed a diastatic skull fracture and one patient only had a linear fracture. At this time, CT scan showed cortical contussion underlying the fracture in every case. The mean time between injury and presentation of GSF was 11.6 weeks. Diagnosis was made by palpation of the cranial defect and confirmed with skull x-rayfilms. The most frecuent location of GSF was in the parietal region. Associated lesions like hydrocephalus, encephalomalacia, lepto-menigeal cysts, brain tissue herniation and ipsilateral ventricular dilatation, were found in the preoperative CT or MRI. All patients underwent a dural repair with pericranium or fascia lata. The cranial defect was covered with local calvarial bone fragments in every case. Only one patient needed a cranioplasty with titanium mesh. Every child with a skull fracture must be followed until the fracture heals. Patients under the age of 3 years with a diastatic fracture and a dural tear, demostrated by TC or MRI, are more prone to develop GSF. In these cases, early repair must be adviced in order to prevent progressive brain damage.

Background: The necessity of a qualitative screening has arisen from the fact that good technical quality is of fundamental importance for evaluating initial pneumoconiosis, for reducing inter- and intra-reader variability, for effective secondary prevention and for forensic medicine purposes., Objectives: The authors report experience in use of a method to evaluate the quality of chest radiographs performed in health surveillance programs for workers at risk for development of pneumoconiosis., Methods: 747 postero-anterior chest radiographs concerning employees of 21 ceramic factories in the Province of Viterbo were examined. A standardized pattern was created for this evaluation. The pattern considers the main factors that can influence the quality of chest radiographs and assigns points for each of them. That factors are: 1) reproduced image of the lung's vascular structure, chiefly in the peripheral portions; 2) reproduced image of heart border, aorta, diaphragm; 3) deep inspiration; 4) symmetric image of the chest; 5) position of the scapulae; 6) visualization of the costal-phrenic angles; 7) technical impairments., Results: The application of the method revealed that half of the chest radiographs examined had poor image quality for a suitable reading, in conformity with the ILO 1980 guidelines. The critical points are poor visualization of the lung's vascular structure due to overexposure or underexposure, technical impairments, non-correct scapulae position., Conclusions: The authors believe that the suggested method can be a useful instrument for self-testing the quality of chest radiographs performed in radiology centers and for the National Health Service to test the quality of chest radiographs performed in health surveillance programs.

The most common complications after CSF shunting to treat hydrocephalus are shunt infection and obstruction. Although ventriculoperitoneal (VP) diversion of the CSF using artificial shunt devices is an accepted method for the management of hydrocephalus, high rates of various complications have been reported, ranging from 24% to 47%. Among these, abdominal complications account for approximately 25%. The incidence of bowel perforation by shunt-catheter is known to be as low as 0.1-0.7%. We describe a case of migration af a peritoneal catheter through a congenital hernia of Morgagni.

The parasitic infection neurocysticercosis may give rise to a variety of psychiatric manifestations that resemble, but are different from, primary psychiatric disorders. The aim of this study was to determine if among individuals from a neurocysticercosis-endemic area of Colombia who apparently had a psychiatric manifestation with associated neurological finding ('cases'), some could have been infected with Taenia solium cysticerci. This case-control study was done in individuals hospitalized in two mental institutions. The control-1 individuals were those classified with primary psychiatric disease, and the control-2 group consisted of healthy, non-hospitalized individuals. A serological test for cysticercosis was positive in 5/96 (5.1%) cases, 4/153 (2.6%) psychiatric controls, and 5/246 (2%) healthy controls. The data analysis indicated a weak association between the cases and a positive serology for neurocysticercosis (odds ratio > 2; P > 0.05). The lower education level of the cases influenced this association.

Many of the resistance mechanisms of enterobacteria to antimicrobial agents are well understood; nevertheless several aspects remain unsolved, particularly with regard to prediction of clinical response. The resistance pattern observed in the antibiogram of a specific organism should be the sum of the natural resistance pattern, characteristic of the species, plus the acquired resistance. In enterobacteria the principal mechanism of resistance to beta lactams and aminoglycosides is enzyme production, Each enzyme recognizes one or more specific beta lactam or aminoglycoside, as a substrate. This translates as a specific resistance phenotype that allows one to infer the enzyme(s) implicated. Enzyme resistance is not, however, the only mechanism of resistance to these agents; often the pattern observed is multifactorial. Resistance to quinolones is due to point and sequence mutations which may be selected by initially active fluoroquinolones and cause a stepwise increase of resistance.

Calmodulin-binding sites on target proteins show considerable variation in primary sequence; hence compounds that block the access of calmodulin to these binding sites may be more selective than compounds that inactivate calmodulin. Suramin and its analogue NF307 inhibit the interaction of calmodulin with the ryanodine receptor. We have investigated whether inhibition of calmodulin binding to target proteins is a general property of these compounds. Suramin inhibited binding of [(125)I]calmodulin to porcine brain membranes and to sarcoplasmic reticulum from skeletal muscle (IC(50)=4.9+/-1.2 microM and 19.9+/-1.8 microM, respectively) and blocked the cross-linking of [(125)I]calmodulin to some, but not all, target proteins in brain membranes by [(125)I]calmodulin. Four calmodulin-binding proteins were purified [ryanodine receptor-1 (RyR1) from rabbit skeletal muscle, neuronal NO synthase (nNOS) from Sf9 cells, G-protein betagamma dimers (Gbetagamma) from porcine brain and a glutathione S-transferase-fusion protein comprising the C-terminal calmodulin-binding domain of the metabotropic glutamate receptor 7A (GST-CmGluR7A) from bacterial lysates]. Three of the proteins employed (Gbetagamma, GST-CmGluR7A and RyR1) display a comparable affinity for calmodulin (in the range of 50-70 nM). Nevertheless, suramin and NF307 only blocked the binding of Gbetagamma and RyR1 to calmodulin-Sepharose. In contrast, the association of GST-CmGluR7A and nNOS was not impaired, whereas excess calmodulin uniformly displaced all proteins from the matrix. Thus suramin and NF307 are prototypes of a new class of calmodulin antagonists that do not interact directly with calmodulin but with calmodulin-recognition sites. In addition, these compounds discriminate among calmodulin-binding motifs.

1. Nicotine and its main derivative. cotinine, are reported to have distinct central activities in mammals. In this study, the cotinine receptor was separated by biochemical procedures including radio receptor, affinity-chromatography, SDS-PAGE, and N-terminal sequencing assays. 2. Consistently, the results showed that distinctive cotinine receptors exist in different tissues of mammals. In rat brain, the affinity chromatography and [125I]cotinine receptor essays were used to isolate a 40-kDa protein (p40) with higher affinity for cotinine than alpha-bungarotoxin and nicotine. The N-terminus amino acid sequences of the p40 and its internal tryptic peptides showed no identity to recently described protein sequences, with the exception of homology to the human p205 synovial fluid protein. 3. These results, in agreement with other behavioral studies, are the first molecular evidence for distinctive nicotine and cotinine receptors in mammals.

Signaling by D(2)-dopamine receptors in neurons likely proceeds in the presence of Ca(2+) oscillations. We describe here the biochemical basis for a cross-talk between intracellular Ca(2+) and the D(2) receptor. By activation of calmodulin (CaM), Ca(2+) directly inhibits the D(2) receptor; this conclusion is based on the following observations: (i) The receptor contains a CaM-binding motif in the NH(2)-terminal end of the third loop, a domain involved in activating G(i/o). A peptide fragment encompassing this domain (D2N) bound dansylated CaM in a Ca(2+)-dependent manner (K(D) approximately 0.1 micrometer). (ii) Activation of purified Galpha(i1) by D2N, and D(2) receptor-promoted GTPgammaS (guanosine 5'-(3-O-thio)triphosphate) binding in membranes was suppressed by Ca(2+)/CaM (IC(50) approximately 0.1 micrometer). (iii) If Ca(2+) influx was elicited in D(2) receptor-expressing HEK293 cells, agonist-dependent inhibition of cAMP formation decreased. This effect was not seen with other G(i)-coupled receptors (A(1)-adenosine and Mel(1A)-melatonin receptor). (iv) The D(2) receptor was retained by immobilized CaM and radiolabeled CaM was co-immunoprecipitated with the receptor. Specifically, inhibition by CaM does not result from uncoupling the D(2) receptor from its cognate G protein(s); rather, CaM directly targets the D(2) receptor to block the receptor-operated G protein activation switch.

UTP stimulates transmitter release and inhibits M-type K(+) channels in rat superior cervical ganglion neurons via G protein-coupled P2Y receptors. To investigate the underlying signaling mechanisms, we treated the neurons with either pertussis or cholera toxin; neither treatment altered the inhibition of M-type K(+) channels by 10 microM UTP. However, pertussis toxin reduced UTP-evoked [(3)H]noradrenaline release by 66%. UTP, UDP, ATP, and ADP caused accumulation of inositol trisphosphate in a pertussis toxin-insensitive manner. Pharmacological inhibition of inositol trisphosphate-induced Ca(2+) release (by inhibition of phospholipase C, of inositol trisphosphate receptors, and of the endoplasmic Ca(2+)-ATPase) prevented the UTP-dependent inhibition of M currents but failed to alter UTP-evoked [(3)H]noradrenaline release. Chelation of intracellular Ca(2+) by 1,2-bis(2-aminophenoxy)ethane-N, N,N',N'-tetraacetic acid also reduced the inhibition of M currents by UTP. In addition, all these manipulations attenuated the inhibition of M currents by bradykinin, but hardly affected the inhibitory action of oxotremorine M. These results demonstrate that UTP inhibits M-type K(+) channels via an inositol trisphosphate-dependent signaling cascade that is also used by bradykinin but not by muscarinic acetylcholine receptors. In contrast, the secretagogue action of UTP is largely independent of this signaling cascade but involves pertussis toxin-sensitive G proteins. Thus, UTP-sensitive P2Y receptors excite sympathetic neurons via at least two different signal transduction mechanisms.

Glutamatergic neurotransmission is controlled by presynaptic metabotropic glutamate receptors (mGluRs). A subdomain in the intracellular carboxyl-terminal tail of group III mGluRs binds calmodulin and heterotrimeric guanosine triphosphate-binding protein (G protein) betagamma subunits in a mutually exclusive manner. Mutations interfering with calmodulin binding and calmodulin antagonists inhibit G protein-mediated modulation of ionic currents by mGluR 7. Calmodulin antagonists also prevent inhibition of excitatory neurotransmission via presynaptic mGluRs. These results reveal a novel mechanism of presynaptic modulation in which Ca(2+)-calmodulin is required to release G protein betagamma subunits from the C-tail of group III mGluRs in order to mediate glutamatergic autoinhibition.

Heterotrimeric G proteins couple membrane-bound heptahelical receptors to their cellular effector systems (ion channels or enzymes generating a second messenger). In current pharmacotherapy, the input to G protein-regulated signalling is typically manipulated by targeting the receptor with appropriate agonists or antagonists and, to a lesser extent, by altering second messenger levels, most notably by inhibiting phosphodiesterases that hydrolyse cyclic nucleotides. When stimulated, G proteins undergo a cycle of activation and deactivation in which the alpha-subunits and the betagamma-dimers sequentially expose binding sites for their reaction partners (receptors, guanine nucleotides and effectors, as well as regulatory proteins). These domains can be blocked by inhibitors and this produces effects that cannot be achieved by receptor antagonists. Here, the structural and mechanistic information on G protein antagonists is summarized and an outline of the arguments supporting the hypothesis that G proteins per se are also potential drug targets is provided.

Objective: To determine the effect of various psychological and social factors--family function, social support, psychological malaise and social class--on frequency of attendance., Design: Study with cases and controls., Setting: Health Districts Girona-3 and La Bisbal., Participants: Criteria for inclusion: being older than 14, being on a list as a user, and having been seen at least once during the study period. The person over-attending is defined as someone attending 7 or more times in a year. The normal attender attends less than 7 times. The sample was 441 patients (209 cases and 232 controls)., Measurements and Main Results: The Smilkestein family Apgar and the DUKE-UNC social support questionnaires, and the Goldberg anxiety and depression scale, were administered. Social class was defined according to the job of the head of the family. Statistical analysis was undertaken in two steps: firstly, bivariate analysis; and second, multivariate. The social support and age variables were related to frequency of attendance: they explained 8.1% of it (through multiple regression). Depression increased by between 1.21 and 2.58 the risk of over-attending and explained 10.53% of the variability of over-attendance, in line with the logistical regression analysis., Conclusions: The psychological and social variables studied fail to explain most of the variability. We should demystify the importance of psychological and social factors in the use of health resources.

Laparoscopy-guided reversal of Hartmann's procedure was performed in eleven patients who had been treated surgically for inflammatory disease or cancer of the colon. Restoration of intestinal continuity was achieved in ten of them. There were no postoperative complications. The mean surgical time was 144 minutes and the mean duration of postoperative ileus was 48 hours (range: 30 to 60 hours). The mean hospital stay was 7 days. Our results suggest that laparoscopic reversal of Hartmann's procedure is safer than and as effective as open surgery.

Objective: To study the immediate and early postoperative results obtained in patients subjected to laparoscopic resection of colorectal cancer., Patients and Method: A prospective, observational cohort study was initiated in January 1993, involving 50 patients subjected to laparoscopic resection for colorectal adenocarcinoma (rectal amputation in 10 cases, lower rectal resection in 13, recto-sigmoidectomy in 18, and miscellaneous colectomies in 9 cases). Seventy-percent of the tumors were in IUCC stages II and III. Mean follow-up was 21 months., Results: Conversion to open surgery was required in 18 cases (36%). Intraoperative problems were limited to a single urethral lesion, while postoperative complications were recorded in 11 patients (22%), and were managed conservatively: a urinary fistula secondary to the aforementioned urethral lesion; subclinical dehiscence of the anastomosis (2 cases); phlebitis (1 case); infection of the surgical wound (4 cases), and urinary and pulmonary infection (1 case each). There were no differences between converted surgery (i.e., conventional laparotomy) and those operations completed endoscopically (with a final assisted or combined minilaparotomy) in terms of the length of the surgical resection piece, the length of the distal margin of the specimen or the number of lymph nodes. Global hospital stay ranged from 9-12 days, versus 5-7 in the group without complications. Global survival is 78% at 42 months, with a disease-free interval of 53% at this time., Conclusions: Laparoscopic colorectal resection presents an incidence of intra- and postoperative complications characteristic of major surgery, with no differences in surgical specimen size with respect to those operations converted to laparotomy. Global survival is similar to that reported in the literature for open surgery.

Suramin analogues uncouple two Gi/Go-coupled receptors, the D2 dopamine receptor in rat striatum and the A1 adenosine receptor in human cerebral cortex, with distinct structure-activity relations. This discrepancy may reflect true differences in the affinity of the analogues for specific receptor/G protein complexes or may be attributable to differences in species or in the tissue source used. We addressed this question by using human embryonic kidney 293 cells that stably express the human A1 and rat A1 receptor and the human D2 receptor. Suramin is 10-fold more potent than its didemethylated analogue NF037 in inhibiting the interaction between G proteins and the rat A1 or human A1 receptor; in contrast, both compounds are equipotent in uncoupling the D2 receptor. These differences are observed regardless of whether (1) inhibition of high affinity agonist binding to the receptors or (2) agonist-stimulated GTPgammaS binding is used as readout, (3) the receptors are allowed to interact with the G protein complement in human embryonic kidney 293 cell membranes, or (4) the receptors are forced to interact with a defined G protein alpha subunit (i.e., after reconstituting pertussis toxin-treated membranes with exogenous rGi alpha-1). The apparent affinity of suramin depends in a linear manner on receptor occupancy, which shows that suramin and the receptor compete for the G protein. Finally, the affinity of the receptors for rGi alpha-1 (human A1 > rat A1 > human D2) is inversely correlated with the potency of suramin in uncoupling ternary complexes formed by these receptors and thus determines the selectivity of the suramin analogues for specific receptor/G protein tandems.