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Background: Various surgical techniques have been devised for the surgical cosmetic enhancement of female outer genitalia. The selection of an optimal method should be based on satisfaction rates and safety; however, comprehensive, contemporary systematic assessment of these factors has been limited in the literature., Objectives: Our aim was to conduct a comprehensive systematic review and meta-analysis to evaluate the overall satisfaction rates and risk factors associated with various labiaplasty techniques and tools., Methods: The authors performed a systematic literature search in 3 medical databases: PubMed, Elsevier, and Cochrane (Central) with the closing date of October 2023. Original articles with quantitative satisfaction rates and frequencies of the most common complications (hematoma, dehiscence, swelling, bleeding, and infection) were included., Results: Systematic search provided a total of 3954 records. After selection and review of the articles, 86 eligible, peer-reviewed studies were identified, of which 53 provided quantitative data. High overall satisfaction rate was found for all methods (proportion [prop] 94%; confidence interval [CI] 93%-95%), with highest satisfaction for deepithelialization (prop 97%; CI, 85%-99%). Complications were generally rare, with elevated incidences for some techniques (wedge resection: dehiscence, prop, 8%, CI 5%-13%; and composite reduction: swelling, prop 13%, CI 2%-54%). Scalpel technique had significantly higher incidence of complications than laser, namely for bleeding, swelling, and hematoma., Conclusions: Labiaplasty can be considered a generally effective approach to outer female genitalia beautification, with low associated risks. Surgeons must tailor their approach to the patients' needs and anatomy to achieve maximal satisfaction, given the differences in the frequency of complications for each method., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Aesthetic Society.)

Objective: This systematic review and meta-analysis compared the accuracy of intraoral scanners and spectrophotometers in determining tooth shade., Materials and Methods: An electronic search of five databases (PubMed, Scopus, Embase, Web of Science, CENTRAL) was conducted on October 19, 2023. A total of 163 studies were identified from the databases, of which 23 articles were eligible for inclusion. In vivo and in vitro quasi-experimental studies were included. After data extraction, a quantitative analysis was performed to determine the accuracy of the intraoral scanner in subgroups using four outcomes: trueness and precision with different measurement locations. A random-effects model was used to pool effect sizes. The pooled proportion with a 95% confidence interval (CI) was used for the effect size measure., Results: Eleven articles were included in the meta-analysis. Trueness with the intraoral scanner was between 0.28 (CI: 0.09-0.60) and 0.38 (CI: 0.24-0.53). Repeatability was between 0.81 (CI: 0.64-0.91) and 0.85 (CI: 0.74-0.92). Trueness showed low, and precision had moderate certainty of evidence., Conclusion: The trueness of shade matching with intraoral scanners is low compared to spectrophotometers, although the precision is considered high and is similar to spectrophotometers., Clinical Significance: Shade determination with intraoral scanners is not recommended., (© 2024 The Author(s). Journal of Esthetic and Restorative Dentistry published by Wiley Periodicals LLC.)

Background/objectives: Autoimmune pancreatitis (AIP) is a diagnosis-challenging disease that often mimics pancreatic malignancy. Pancreatic resection is considered to be a curative treatment for pancreatic ductal adenocarcinoma (PDAC). This meta-analysis aims to study the incidence of AIP in patients who have undergone pancreatic resection for clinical manifestation of cancer., Methods: A comprehensive search was conducted in three databases, PubMed, Embase and the Cochrane Library, using the terms 'autoimmune pancreatitis' and 'pancreatic resection' and supplemented by manual checks of reference lists in all retrieved articles., Results: Ten articles were included in the final analysis. 8917 pancreatic resections were performed because of a clinical suspicion of pancreatic cancer. AIP accounted for 140 cases (1.6%). Type 1 AIP comprised the majority of cases, representing 94% (132 cases), while type 2 AIP made up the remaining 6% (eight cases) after further classification. AIP accounted for almost 26% of all cases of benign diseases involving unnecessary surgery and was overrepresented in males in 70% of cases compared to 30% in females. The mean age for AIP patients was 59 years. Serum CA 19 - 9 levels were elevated in 23 out of 47 (49%) AIP patients, where higher levels were detected more frequently in patients with type 1 AIP (51%, 22 out of 43) than in those with type 2 AIP (25%, 1 out of 4). The sensitivity of IgG4 levels in type 1 AIP was low (43%, 21/49 patients)., Conclusion: Even with modern diagnostic methods, distinguishing between AIP and PDAC can still be challenging, thus potentially resulting in unnecessary surgical procedures in some cases. Serum CA 19 - 9 levels are not useful in distinguishing between AIP and PDAC. Work must thus be done to improve diagnostic methods and avoid unnecessary complicated surgery., (© 2024. The Author(s).)

Fluid resuscitation during diabetic ketoacidosis (DKA) is most frequently performed with 0.9% saline despite its high chloride and sodium concentration. Balanced Electrolyte Solutions (BES) may prove a more physiological alternative, but convincing evidence is missing. We aimed to compare the efficacy of 0.9% saline to BES in DKA management. MEDLINE, Cochrane Library, and Embase databases were searched for relevant studies using predefined keywords (from inception to 27 November 2021). Relevant studies were those in which 0.9% saline (Saline-group) was compared to BES (BES-group) in adults admitted with DKA. Two reviewers independently extracted data and assessed the risk of bias. The primary outcome was time to DKA resolution (defined by each study individually), while the main secondary outcomes were changes in laboratory values, duration of insulin infusion, and mortality. We included seven randomized controlled trials and three observational studies with 1006 participants. The primary outcome was reported for 316 patients, and we found that BES resolves DKA faster than 0.9% saline with a mean difference (MD) of -5.36 [95% CI: -10.46, -0.26] hours. Post-resuscitation chloride (MD: -4.26 [-6.97, -1.54] mmoL/L) and sodium (MD: -1.38 [-2.14, -0.62] mmoL/L) levels were significantly lower. In contrast, levels of post-resuscitation bicarbonate (MD: 1.82 [0.75, 2.89] mmoL/L) were significantly elevated in the BES-group compared to the Saline-group. There was no statistically significant difference between the groups regarding the duration of parenteral insulin administration (MD: 0.16 [-3.03, 3.35] hours) or mortality (OR: -0.67 [0.12, 3.68]). Studies showed some concern or a high risk of bias, and the level of evidence for most outcomes was low. This meta-analysis indicates that the use of BES resolves DKA faster than 0.9% saline. Therefore, DKA guidelines should consider BES instead of 0.9% saline as the first choice during fluid resuscitation., (© 2024 The Author(s). Diabetes/Metabolism Research and Reviews published by John Wiley & Sons Ltd.)

Background: Neoadjuvant therapy is an essential modality for reducing the clinical stage of esophageal cancer; however, the superiority of neoadjuvant chemotherapy (nCT) or neoadjuvant chemoradiotherapy (nCRT) is unclear. Therefore, a discussion of these two modalities is necessary., Aim: To investigate the benefits and complications of neoadjuvant modalities., Methods: To address this concern, predefined criteria were established using the PICO protocol. Two independent authors performed comprehensive searches using predetermined keywords. Statistical analyses were performed to identify significant differences between groups. Potential publication bias was visualized using funnel plots. The quality of the data was evaluated using the Risk of Bias Tool 2 (RoB2) and the GRADE approach., Results: Ten articles, including 1928 patients, were included for the analysis. Significant difference was detected in pathological complete response (pCR) [ P < 0.001; odds ratio (OR): 0.27; 95%CI: 0.16-0.46], 30-d mortality ( P = 0.015; OR: 0.4; 95%CI: 0.22-0.71) favoring the nCRT, and renal failure ( P = 0.039; OR: 1.04; 95%CI: 0.66-1.64) favoring the nCT. No significant differences were observed in terms of survival, local or distal recurrence, or other clinical or surgical complications. The result of RoB2 was moderate, and that of the GRADE approach was low or very low in almost all cases., Conclusion: Although nCRT may have a higher pCR rate, it does not translate to greater long-term survival. Moreover, nCRT is associated with higher 30-d mortality, although the specific cause for postoperative complications could not be identified. In the case of nCT, toxic side effects are suspected, which can reduce the quality of life. Given the quality of available studies, further randomized trials are required., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Purpose: The purpose of this study was to assess the ability of pretreatment PET parameters and peripheral blood biomarkers to predict progression-free survival (PFS) and overall survival (OS) in NSCLC patients treated with ICIT., Methods: We prospectively included 87 patients in this study who underwent pre-treatment [ 18 F]-FDG PET/CT. Organ-specific and total metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were measured using a semiautomatic software. Sites of organ involvement (SOI) were assessed by PET/CT. The log-rank test and Cox-regression analysis were used to assess associations between clinical, laboratory, and imaging parameters with PFS and OS. Time dependent ROC were calculated and model performance was evaluated in terms of its clinical utility., Results: MTV increased with the number of SOI and was correlated with neutrophil and lymphocyte cell count (Spearman's rho = 0.27 or 0.32; p =.02 or 0.003; respectively). Even after adjustment for known risk factors, such as PD-1 expression and neutrophil cell count, the MTV and the number of SOI were independent risk factors for progression (per 100 cm 3 ; adjusted hazard ratio [aHR]: 1.13; 95% confidence interval [95%CI]: 1.01-1.28; p =.04; single SOI vs. ≥ 4 SOI: aHR: 2.26, 95%CI: 1.04-4.94; p =.04). MTV and the number of SOI were independent risk factors for overall survival (per 100 cm 3 aHR: 1.11, 95%CI: 1.01-1.23; p =.03; single SOI vs. ≥ 4 SOI: aHR: 4.54, 95%CI: 1.64-12.58; p =.04). The combination of MTV and the number of SOI improved the risk stratification for PFS and OS (log-rank test p <.001; C-index: 0.64 and 0.67)., Conclusion: The MTV and the number of SOI are simple imaging markers that provide complementary information to facilitate risk stratification in NSCLC patients scheduled for ICIT., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Helmut Prosch reports financial support was provided by MSD. Helmut Prosch reports financial support was provided by Roche. Helmut Prosch reports was provided by AstraZeneca Pharmaceuticals LP. Helmut Prosch reports was provided by Bristol Myers Squibb Co. Helmut Prosch reports financial support was provided by Christian Doppler Laboratories. Lucian Beer reports financial support was provided by Christian Doppler Laboratories., (Copyright © 2023. Published by Elsevier B.V.)

Introduction: There has been a drastic increase in the reported number of people seeking help for gender dysphoria in many countries over the last two decades. Yet, our knowledge of gender dysphoria and related outcomes is restricted due to the lack of high-quality studies employing comprehensive approaches. This longitudinal study aims to enhance our knowledge of gender dysphoria; different aspects will be scrutinised, focusing primarily on the psychosocial and mental health outcomes, prognostic markers and, secondarily, on the underlying mechanisms for its origin., Methods and Analysis: The Swedish Gender Dysphoria Study is an ongoing multicentre longitudinal cohort study with 501 registered participants with gender dysphoria who are 15 years old or older. Participants at different phases of their clinical evaluation process can enter the study, and the expected follow-up duration is three years. The study also includes a comparison group of 458 age- and county-matched individuals without gender dysphoria. Data on the core outcomes of the study, which are gender incongruence and experienced gender dysphoria, body satisfaction and satisfaction with gender-affirming treatments, as well as other relevant outcomes, including mental health, social functioning and life satisfaction, are collected via web surveys. Two different research visits, before and after starting on gender-affirming hormonal treatment (if applicable), are planned to collect respective biological and cognitive measures. Data analysis will be performed using appropriate biostatistical methods. A power analysis showed that the current sample size is big enough to analyse continuous and categorical outcomes, and participant recruitment will continue until December 2022., Ethics and Dissemination: The ethical permission for this study was obtained from the Local Ethical Review Board in Uppsala, Sweden. Results of the study will be presented at national and international conferences and published in peer-reviewed journals. Dissemination will also be implemented through the Swedish Gender Dysphoria Study network in Sweden., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Nowadays, the solution to many practical problems relies on machine learning tools. However, compiling the appropriate training data set for real-world classification problems is challenging because collecting the right amount of data for each class is often difficult or even impossible. In such cases, we can easily face the problem of imbalanced learning. There are many methods in the literature for solving the imbalanced learning problem, so it has become a serious question how to compare the performance of the imbalanced learning methods. Inadequate validation techniques can provide misleading results (e.g., due to data shift), which leads to the development of methods designed for imbalanced data sets, such as stratified cross-validation (SCV) and distribution optimally balanced SCV (DOB-SCV). Previous studies have shown that higher classification performance scores ( AUC ) can be achieved on imbalanced data sets using DOB-SCV instead of SCV. We investigated the effect of the oversamplers on this difference. The study was conducted on 420 data sets, involving several sampling methods and the DTree, kNN, SVM, and MLP classifiers. We point out that DOB-SCV often provides a little higher F 1 and AUC values for classification combined with sampling. However, the results also prove that the selection of the sampler-classifier pair is more important for the classification performance than the choice between the DOB-SCV and the SCV techniques.

In the last 15 years, the segmentation of vessels in retinal images has become an intensively researched problem in medical imaging, with hundreds of algorithms published. One of the de facto benchmarking data sets of vessel segmentation techniques is the DRIVE data set. Since DRIVE contains a predefined split of training and test images, the published performance results of the various segmentation techniques should provide a reliable ranking of the algorithms. Including more than 100 papers in the study, we performed a detailed numerical analysis of the coherence of the published performance scores. We found inconsistencies in the reported scores related to the use of the field of view (FoV), which has a significant impact on the performance scores. We attempted to eliminate the biases using numerical techniques to provide a more realistic picture of the state of the art. Based on the results, we have formulated several findings, most notably: despite the well-defined test set of DRIVE, most rankings in published papers are based on non-comparable figures; in contrast to the near-perfect accuracy scores reported in the literature, the highest accuracy score achieved to date is 0.9582 in the FoV region, which is 1% higher than that of human annotators. The methods we have developed for identifying and eliminating the evaluation biases can be easily applied to other domains where similar problems may arise., 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 © 2021 Elsevier B.V. All rights reserved.)

Objectives: Although spontaneous breathing trials (SBTs) are standard of care to extubation readiness, no tool exists that optimises prediction and standardises assessment. In this study, we evaluated the feasibility and clinical impressions of Extubation Advisor (EA), a comprehensive clinical extubation decision support (CDS) tool., Design: Phase I mixed-methods observational study., Setting: Two Canadian intensive care units (ICUs)., Participants: We included patients on mechanical ventilation for ≥24 hours and clinicians (respiratory therapists and intensivists) responsible for extubation decisions., Interventions: Components included a predictive model assessment, feasibility evaluation, questionnaires and interviews with clinicians., Results: We enrolled 117 patients, totalling 151 SBTs and 80 extubations. The incidence of extubation failure was 11% in low-risk patients and 21% in high-risk patients stratified by the predictive model; 38% failed extubation when both the model and clinical impression were at high risk. The tool was well rated: 94% and 75% rated the data entry and EA report as average or better, respectively. Interviews (n=15) revealed favourable impressions regarding its user interface and functionality, but unexpectedly, also concerns regarding EA's potential impact on respiratory therapists' job security., Conclusions: EA implementation was feasible, and users perceived it to have potential to support extubation decision-making. This study helps to understand bedside implementation of CDS tools in a multidisciplinary ICU., Trial Registration Number: NCT02988167., Competing Interests: Competing interests: AJES is the Founder and Board Chair of Therapeutic Monitoring Systems (TMS); TMS is developing and commercialising waveform-based variability-derived clinical decision support tools in order to improve care for patients at risk for or with existing critical illness. Both AJES and CLH are co-inventors on patents related to physiological waveform assessment and variability analysis. All remaining authors have disclosed that they do not have any potential conflicts of interest., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The so-called sports consumption models are looking for the factors that influence the sports spending of households. This paper aims to examine the Hungarian, Polish and German households' sports expenditures which can be an important indicator of physical activity and sporty lifestyle., Methods: Surveying of households in three countries (Hungary, Poland and Germany) has been conducted with a self-designed questionnaire. We have used descriptive and bivariate non-parametric and parametric statistical methods: (1) χ 2 test, Mann-Whitney test and Kruskal-Wallis test for checking the relationship between sociodemographic and physical activity variables and (2) independent sample t-test and ANOVA for checking the differences in sports expenditures., Results: Our research concluded that men, especially previous athletes, exercise more than women and those who have no history as registered athletes. The choice of sports venues is obviously different between the countries in the sample. Members of the study population spend the most on sports services while they spend the least on sports equipment. German households have the highest spending rates compared to the other two countries., Conclusions: Results are in line with our previous research findings and with other literatures. The difference in preferences of sports venues could have the reason of different supply of sports clubs or the different living standards too. It needs further researches to clear it. Material wealth, income level and sport socialisation can be a determining factor regarding the level of sports spending.

This study primarily focuses on the assessment of dentistry students' improvement of manual skills resulting from their participation in courses. We aimed to prove that systematic manual skills development significantly improves dexterity. We hypothesized that the dexterity training regimen improves manual dexterity demonstrated by the HAM-Man (Hamburg Assessment Test for Medicine-Manual Dexterity) test scores and CGM (cerebellar grey matter) growth. Thirty volunteers were randomly divided into two equal groups (study and control). Firstly, volunteers were examined by the HAM-Man test and baseline MRI scans. Afterwards, a manual skills development course was launched for the "study group". Secondly, all the manual skills of the students were evaluated longitudinally, by the HAM-Man test. Simultaneously, the follow-up MRI scans were taken to observe morphologic changes in the cerebellum. The Wilcoxon signed-rank test and Student Paired t-test were used for statistical analyses. Value p < 0.05 was considered significant. After the training, significant growth of CGM as well as improvement on manual skill assessment tests, were found in the study group. Training courses are suitable for preparing students with low levels of dexterity for performing demanding tasks. The improvement is demonstrable by a wire bending test and by bilateral CGM enlargement as well.

Background: Despite curative intent resection in patients with non-small cell lung cancer (NSCLC), recurrence leading to mortality remains too common. Melatonin has shown promise for the treatment of patients with lung cancer; however, its effect following cancer resection has not been studied. We evaluated if melatonin taken after complete resection reduces lung cancer recurrence and mortality, or impacts quality of life (QOL), symptomatology or immune function., Methods: Participants received melatonin (20 mg) or placebo nightly for one year following surgical resection of primary NSCLC. The primary outcome was two-year disease-free survival (DFS). Secondary outcomes included five-year DFS, adverse events, QOL, fatigue, sleep, depression, anxiety, pain, and biomarkers assessing for immune function/inflammation. This study is registered at https://clinicaltrials.gov NCT00668707., Findings: 709 patients across eight centres were randomized to melatonin ( n  = 356) versus placebo ( n  = 353). At two years, melatonin showed a relative risk of 1·01 (95% CI 0·83-1·22), p  = 0·94 for DFS. At five years, melatonin showed a hazard ratio of 0·97 (95% CI 0·86-1·09), p  = 0·84 for DFS. When stratified by cancer stage (I/II and III/IV), a hazard reduction of 25% (HR 0·75, 95% CI 0·61-0·92, p  = 0·005) in five-year DFS was seen for participants in the treatment arm with advanced cancer (stage III/IV). No meaningful differences were seen in any other outcomes., Interpretation: Adjuvant melatonin following resection of NSCLC does not affect DFS for patients with resected early stage NSCLC, yet may increase DFS in patients with late stage disease. Further study is needed to confirm this positive result. No beneficial effects were seen in QOL, symptoms, or immune function., Funding: This study was funded by the Lotte and John Hecht Memorial Foundation and the Gateway for Cancer Research Foundation., Competing Interests: Dr. Villeneuve reports ‘other’ from Minogue Medical, outside the submitted work. All other authors have no conflicts of interest to disclose., (© 2021 The Authors.)

The Transgender Congruence Scale (TCS) is a non-binary tool used in Sweden for gender dysphoria (GD) assessment; however, its Swedish version has not been validated. To investigate the psychometric properties of the TCS, its capacity to distinguish individuals with GD and its concurrent validity compared to other scales. Patients with GD (n = 135) and controls (n = 443) filled in a questionnaire containing sociodemographic questions, the TCS, the Utrecht Gender Dysphoria Scale (UGDS), and the Gender Identity/Gender Dysphoria Questionnaire for Adolescents and Adults (GIDYQ-AA). TCS had good discriminatory validity and internal consistency. Patients with GD, stratified by birth-assigned sex, had lower TCS scores compared to controls. Confirmatory factor analysis (CFA) supported the two-factor model of the TCS. Multiple-group CFA suggested measurement invariance between birth-assigned sexes and configural invariance between patients with GD and controls. Area under the ROC curve for birth-assigned males was 0.991 and for females 0.994. A TCS mean value of three provided sensitivity 94.3% and 95.1% as well as specificity 98.6% and 98% for aM and aF, respectively. The TCS was significantly correlated to UGDS and GIDYQ-AA. The TCS may be a valuable tool in the clinical assessment of individuals with GD.

Tumor dissemination and recurrence is attributed to highly resistant cancer stem cells (CSCs) which may constitute a fraction of circulating tumor cells (CTCs). Small cell lung cancer (SCLC) constitutes a suitable model to investigate the relation of CTCs and CSCs due to rapid tumor spread and a high number of CTCs. Expansion of five SCLC CTC lines (BHGc7, 10, 16, 26 and UHGc5) in vitro at our institution allowed for the analysis of CSC markers and cytotoxicity of the CSC-selective drugs salinomycin and niclosamide against CTC single cell suspensions or CTC spheroids/ tumorospheres (TOS). Salinomycin exerted dose-dependent cytotoxicity against the SCLC lines but, with exception of BHGc7 TOS, there was no markedly enhanced activity against TOS. Similarly, niclosamide exhibits high activity against BHGc7 TOS and UHGc5 TOS but not against the other CTC spheroids. High expression of the CSC marker CD133 was restricted to three SCLC tumor lines and the BHGc10 CTC line. All SCLC CTCs are CD24-positive but lack expression of CD44 and ABCG2 in contrast to the SCLC tumor lines which show a phenotype more similar to that of CSCs. The stem cell marker SOX2 was found in all CTC lines and SCLC GLC14/16, whereas elevated expression of Oct-3/4 and Nanog was restricted to BHGc26 and UHGc5. In conclusion, the SCLC CTCs established from patients with relapsed disease lack a typical CSC phenotype in respect to chemosensitivity to CSC-selective drugs, surface markers, expression of pluripotent stem cell and transcription factors.

Innovative tools are essential for advancing malaria control and depend on an understanding of molecular mechanisms governing transmission of malaria parasites by Anopheles mosquitoes. CRISPR/Cas9-based gene disruption is a powerful method to uncover underlying biology of vector-pathogen interactions and can itself form the basis of mosquito control strategies. However, embryo injection methods used to genetically manipulate mosquitoes (especially Anopheles ) are difficult and inefficient, particularly for non-specialist laboratories. Here, we adapted the ReMOT Control ( Re ceptor- m ediated O vary T ransduction of C argo) technique to deliver Cas9 ribonucleoprotein complex to adult mosquito ovaries, generating targeted and heritable mutations in the malaria vector Anopheles stephensi without injecting embryos. In Anopheles , ReMOT Control gene editing was as efficient as standard embryo injections. The application of ReMOT Control to Anopheles opens the power of CRISPR/Cas9 methods to malaria laboratories that lack the equipment or expertise to perform embryo injections and establishes the flexibility of ReMOT Control for diverse mosquito species., (Copyright © 2020 Macias et al.)

The second-generation ALK tyrosine kinase inhibitor brigatinib has recently been approved in the European Union for use after crizotinib treatment in patients with EML4-ALK-rearranged lung cancer. In the current study, brigatinib was investigated as second-line or later-line treatment in 35 patients who had developed resistance to crizotinib, ceritinib, or alectinib. Most patients (68.6%) received brigatinib as second or third line (range: second to 12th line). In the total cohort, complete and partial responses were obtained for 9.1 and 75.8%, respectively. Overall median progression-free survival was 9.9 months, whereas the largest treatment cohort (brigatinib after crizotinib failure) showed a median progression-free survival of 8.4 months. Fifty-four percent of patients with baseline brain metastases responded to brigatinib treatment. Brigatinib was highly effective after crizotinib and ceritinib failure. Six patients had received alectinib as monotherapy, second-line, or third line before brigatinib; of these, four experienced partial responses and two progressed responses. Brigatinib treatment was well tolerated.

The next generation of Intelligent Transportation Systems (ITS) will strongly rely on a high level of detail and coverage in traffic data acquisition. Beyond aggregated traffic parameters like the flux, mean speed, and density used in macroscopic traffic analysis, a continuous location estimation of individual vehicles on a microscopic scale will be required. On the infrastructure side, several sensor techniques exist today that are able to record the data of individual vehicles at a cross-section, such as static radar detectors, laser scanners, or computer vision systems. In order to record the position data of individual vehicles over longer sections, the use of multiple sensors along the road with suitable synchronization and data fusion methods could be adopted. This paper presents appropriate methods considering realistic scale and accuracy conditions of the original data acquisition. Datasets consisting of a timestamp and a speed for each individual vehicle are used as input data. As a first step, a closed formulation for a sensor offset estimation algorithm with simultaneous vehicle registration is presented. Based on this initial step, the datasets are fused to reconstruct microscopic traffic data using quintic Beziér curves. With the derived trajectories, the dependency of the results on the accuracy of the individual sensors is thoroughly investigated. This method enhances the usability of common cross-section-based sensors by enabling the deriving of non-linear vehicle trajectories without the necessity of precise prior synchronization.

Purpose: The aim of this study was to compare the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, the immune RECIST (iRECIST) criteria, and the Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST) 1.0 in patients with advanced non-small cell lung cancer treated with programmed cell death protein 1 (PD-1)/programmed cell death protein 1 ligand (PD-L1) inhibitors., Methods: This prospective study of 42 patients treated with a PD-1/PD-L1 inhibitor was approved by our institutional review board, and all patients gave written, informed consent. Tumor burden dynamics were assessed on F-FDG PET/CT before and after treatment initiation. Immunotherapeutic responses were evaluated according to RECIST 1.1, iRECIST, and PERCIST 1.0 for the dichotomous groups, responders versus nonresponders. Cohen κ and Wilcoxon signed rank tests were used to evaluate concordance among these criteria. We assessed progression-free survival and overall survival using the Kaplan-Meier estimator., Results: The RECIST 1.1 and PERCIST 1.0 response classifications were discordant in 6 patients (14.2%; κ = 0.581). RECIST 1.1 and iRECIST were discordant in 2 patients, who evidenced pseudoprogression after treatment initiation. Median progression-free survival, as well as overall survival, was significantly longer for responders compared with nonresponders for all criteria (P < 0.001), with no significant difference between the 3 criteria (P > 0.05)., Conclusions: RECIST 1.1 and PERCIST 1.0 show only moderate agreement, but both can predict treatment response to PD-1/PD-L1 inhibitor therapy. In case of pseudoprogression, metabolic tumor activity may help to correctly classify treatment response.

Background: Use of complementary therapies is high among people with cancer despite research gaps. The Thoracic Peri-Operative Integrative Surgical Care Evaluation (POISE) Trial will evaluate the impact of an integrative care intervention delivered by naturopathic doctors (NDs) in conjunction with usual care for patients undergoing surgery for lung, gastric, and esophageal cancer., Objectives: To describe the multistep, multidisciplinary process of defining the integrative care intervention to be used in the Thoracic POISE trial using a principle-based approach that is pragmatic, holistic, safe, feasible, evidence driven, and consensus based., Methods: An Intervention Development Committee (IDC) made up of a multidisciplinary team of health care providers (NDs, surgeons, oncologists, nurses, dietitians, physiotherapists, pharmacists, and psychologists), researchers, and patients was established to oversee the process. Potential intervention components were identified through a clinical practice survey and expert opinion. Systematic literature reviews were conducted and scores assigned based on the following criteria: usage, safety, goals, feasibility/scalability, and evidence. The IDC selected an intervention to be piloted that consists of a standard palette including core and optional components. Safety, known risks, and interactions with pharmaceuticals were evaluated using industry and professional monographs, a scoping literature review, and consultations with hospital pharmacists., Results: The clinical practice survey and expert opinion identified 28 components for consideration. Following literature reviews, scoring, consensus from the IDC, and safety and interaction considerations, an intervention palette consisting of core and optional components was defined. The intervention options vary based on the patient's phase of treatment and symptom-specific needs. The intervention includes supplements, physical recommendations (exercise), nutritional counseling, and psychological support (audio scripts)., Conclusion: Through a multistep, multidisciplinary process an integrative care intervention was developed for the Thoracic POISE trial. The intervention will be piloted in a single-arm feasibility study, followed by a single-center randomized controlled trial (RCT), and finally a multicenter RCT.

Transposons are a class of selfish DNA elements that can mobilize within a genome. If mobilization is accompanied by an increase in copy number (replicative transposition), the transposon may sweep through a population until it is fixed in all of its interbreeding members. This introgression has been proposed as the basis for drive systems to move genes with desirable phenotypes into target species. One such application would be to use them to move a gene conferring resistance to malaria parasites throughout a population of vector mosquitos. We assessed the feasibility of using the piggyBac transposon as a gene-drive mechanism to distribute anti-malarial transgenes in populations of the malaria vector, Anopheles stephensi. We designed synthetic gene constructs that express the piggyBac transposase in the female germline using the control DNA of the An. stephensi nanos orthologous gene linked to marker genes to monitor inheritance. Two remobilization events were observed with a frequency of one every 23 generations, a rate far below what would be useful to drive anti-pathogen transgenes into wild mosquito populations. We discuss the possibility of optimizing this system and the impetus to do so., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)

In [1], the following support information should have been included in the first footnote.

Genetic engineering technologies can be used both to create transgenic mosquitoes carrying antipathogen effector genes targeting human malaria parasites and to generate gene-drive systems capable of introgressing the genes throughout wild vector populations. We developed a highly effective autonomous Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-associated protein 9 (Cas9)-mediated gene-drive system in the Asian malaria vector Anopheles stephensi, adapted from the mutagenic chain reaction (MCR). This specific system results in progeny of males and females derived from transgenic males exhibiting a high frequency of germ-line gene conversion consistent with homology-directed repair (HDR). This system copies an ∼ 17-kb construct from its site of insertion to its homologous chromosome in a faithful, site-specific manner. Dual anti-Plasmodium falciparum effector genes, a marker gene, and the autonomous gene-drive components are introgressed into ∼ 99.5% of the progeny following outcrosses of transgenic lines to wild-type mosquitoes. The effector genes remain transcriptionally inducible upon blood feeding. In contrast to the efficient conversion in individuals expressing Cas9 only in the germ line, males and females derived from transgenic females, which are expected to have drive component molecules in the egg, produce progeny with a high frequency of mutations in the targeted genome sequence, resulting in near-Mendelian inheritance ratios of the transgene. Such mutant alleles result presumably from nonhomologous end-joining (NHEJ) events before the segregation of somatic and germ-line lineages early in development. These data support the design of this system to be active strictly within the germ line. Strains based on this technology could sustain control and elimination as part of the malaria eradication agenda.

Background: Focal cartilage lesions in the knee joint have limited capacity to heal. Current animal experiments show that incisions of the deep zone of a cartilage allograft allow acceptable integration for the graft., Questions/purposes: We performed this clinical study to determine (1) if the multiply incised cartilage graft is surgically applicable for focal cartilage lesions, (2) whether this allograft has a potential to integrate to the repair site, and (3) if patients show clinical improvement., Patients and Methods: Seven patients with 8 chondral lesions were enrolled into the study. Symptomatic lesions between 2 and 8 cm(2) were accepted. Additional injuries were allowed but were addressed simultaneously. Grafts were tailored to match and the deep zone of the cartilage was multiply incised to augment the basal integration before securing in place. Rigorous postoperative physiotherapy followed. At 12 and 24 months the patients' satisfaction were measured and serial magnetic resonance imaging (MRI) was performed in 6 patients., Results: Following the implantations no adverse reaction occurred. MRI evaluation postoperatively showed the graft in place in 5 out of 6 patients. In 1 patient, MRI suggested partial delamination at 1 year and graft degeneration at 2 years. Short Form-36 health survey and the Lysholm knee score demonstrated a significant improvement in the first year; however, by 2 years there was a noticeable drop in the scores. Conclusions. Multiply incised pure chondral allograft used for cartilage repair appears to be a relatively safe method. Further studies are necessary to assess its potential in cartilage repair before its clinical use.

Background: Myelofibrosis (MF) is characterized by accumulation of stromal cells and extracellular matrix. Progression of fibrosis is an important clinical issue and monitoring is required for new therapeutic approaches. Currently, the quantification is based on semiquantitative evaluation of reticulin silver stained slides. We recently reported that platelet derived growth factor receptor beta (PDGFRβ) expression in fibroblasts is a useful marker of stromal activation. PDGFRβ expression based scores represent significant differences in different MF grade which provides optimal source of quantification. In this study, slide-based measurements were performed to support correlations of PDGFRβ expression with MF grade., Methods: Scanned image tiles from 79 bone marrow samples (BM) with different MF grades were evaluated for PDGFRβ-related IHC parameters. Following the determination of immunopositive (brown component) and total area (region of interest) of the BM, PDGFRβ related image parameters were defined and evaluated in comparison with the classical reticulin based grading., Results: Eight PDGFRβ expression related image parameters showed excellent correlation with the MF grade (correlation coefficient ranging between 0.79 and 0.83) and with PDGFRβ score (0.76-0.87). Despite the significant sample heterogeneity, the parameters showed significant differences between fibrotic and nonfibrotic cases and between mild and advanced fibrosis. Distribution of values within a particular specimen emphasizes the heterogeneity of bone marrow involvement which may cause difficulties in semiquantitative methods., Conclusions: Our results clearly demonstrated the correlation between MF and PDGFRβ expression considering all relevant areas in BM samples. This method provides good basis for follow-up comparison of the fibrotic samples., (© 2014 Clinical Cytometry Society.)

Introduction: Prolonged ventilation and failed extubation are associated with increased harm and cost. The added value of heart and respiratory rate variability (HRV and RRV) during spontaneous breathing trials (SBTs) to predict extubation failure remains unknown., Methods: We enrolled 721 patients in a multicenter (12 sites), prospective, observational study, evaluating clinical estimates of risk of extubation failure, physiologic measures recorded during SBTs, HRV and RRV recorded before and during the last SBT prior to extubation, and extubation outcomes. We excluded 287 patients because of protocol or technical violations, or poor data quality. Measures of variability (97 HRV, 82 RRV) were calculated from electrocardiogram and capnography waveforms followed by automated cleaning and variability analysis using Continuous Individualized Multiorgan Variability Analysis (CIMVA™) software. Repeated randomized subsampling with training, validation, and testing were used to derive and compare predictive models., Results: Of 434 patients with high-quality data, 51 (12%) failed extubation. Two HRV and eight RRV measures showed statistically significant association with extubation failure (P <0.0041, 5% false discovery rate). An ensemble average of five univariate logistic regression models using RRV during SBT, yielding a probability of extubation failure (called WAVE score), demonstrated optimal predictive capacity. With repeated random subsampling and testing, the model showed mean receiver operating characteristic area under the curve (ROC AUC) of 0.69, higher than heart rate (0.51), rapid shallow breathing index (RBSI; 0.61) and respiratory rate (0.63). After deriving a WAVE model based on all data, training-set performance demonstrated that the model increased its predictive power when applied to patients conventionally considered high risk: a WAVE score >0.5 in patients with RSBI >105 and perceived high risk of failure yielded a fold increase in risk of extubation failure of 3.0 (95% confidence interval (CI) 1.2 to 5.2) and 3.5 (95% CI 1.9 to 5.4), respectively., Conclusions: Altered HRV and RRV (during the SBT prior to extubation) are significantly associated with extubation failure. A predictive model using RRV during the last SBT provided optimal accuracy of prediction in all patients, with improved accuracy when combined with clinical impression or RSBI. This model requires a validation cohort to evaluate accuracy and generalizability., Trial Registration: ClinicalTrials.gov NCT01237886. Registered 13 October 2010.

Background: Myelofibrosis (MF) is characterized by accumulation of stromal cells and extracellular matrix. Progression of fibrosis is an important clinical issue and monitoring is required for new therapeutic approaches. Currently the quantification is based on semi-quantitative evaluation of reticulin silver stained slides. We recently reported that platelet derived growth factor receptor beta (PDGFRβ) expression in fibroblasts is a useful marker of stromal activation. PDGFRβ expression based scores represent significant differences in different myelofibrosis grade which provides optimal source of quantification. In this study slide based measurements were performed in order to support correlations of PDGFRβ expression with MF grade. Methods: Scanned image tiles from 79 bone marrow samples (BM) with different myelofibrosis grades were evaluated for PDGFRβ-related IHC parameters. Following the determination of immunopositive (brown component) and total area (region of interest) of the BM, PDGFRβ related image parameters were defined and evaluated in comparison to the classical reticulin based grading. Results: Eight PDGFRβ expression related image parameters showed excellent correlation with the MF grade (correlation coefficient ranging between 0.79 and 0.83) and with PDGFRβ score (0.76-0.87). Despite the significant sample heterogeneity the parameters showed significant differences between fibrotic and non-fibrotic cases and between mild and advanced fibrosis. Distribution of values within a particular specimen emphasizes the heterogeneity of bone marrow involvement which may cause difficulties in semi-quantitative methods. Conclusions: Our results clearly demonstrated the correlation between myelofibrosis and PDGFRβ expression considering all relevant areas in BM samples. This method provides good basis for follow-up comparison of the fibrotic samples. © 2014 Clinical Cytometry Society., (Copyright © 2014 Clinical Cytometry Society.)

A 68-year-old nonsmoking male patient with thin gingival biotype presented for treatment of mobile mandibular left premolars. Extraction of teeth and immediate dental implant placement has been suggested. To prevent vestibular gingival recession and insure tissue stability by increasing thickness of marginal gingiva, acellular dermal matrix allograft was applied using the coronally advanced modified tunnelling technique. Six months later premolars were extracted, immediately replaced with implants and temporary crowns. After another four months, definitive gold ceramic crowns were cemented on prefabricated titanium abutments. Due to the altered gingival biotype and application of the platform switching phenomenon no vertical bone resorption and gingival recession was recorded at 6, 12 and 24 month follow-up with a well acceptable esthetic appearance.

VEGF induces proliferation of endothelial cells, stimulates angiogenesis, and increases vascular permeability in many organs. Nevertheless, we have only limited information about its role on gingival hemodynamics, especially in venules. Therefor the aim of this study was to assess the acute circulatory effects of VEGF on rat gingival venules by means of the following protocol. Wister rats (n=63) were devided into five study groups after anesthesia; each animal received 10 microl of experimental solution dripped onto the lower interincisal gingiva. The groups included: 1) saline control (after the experiment, gingiva was excised for VEGF receptor 2 [VEGFR2] immunohistochemistry); 2) VEGF (0.1, 1, 10, or 50 microg/ml); 3) VEGF2 receptor antagonist 5-((7-benzyloxyquinazolin-4-yl)amino)-4-fluoro-2-methyl-phenol-hydrochloride (ZM323881; 20 microg/ml); 4) ZM323881 (20 microg/ml) followed by VEGF application (50 microg/ml after 15 minutes); and 5) VEGF (10 microg/ml), these rats were premedicated with nitric oxide (NO) synthase blocker (NG-nitro-L-arginine-methyl-ester [L-NAME]; 1 mg/ml in drinking water) for 1 week before the experiment. Changes in gingival superficial venule diameter were measured by vital microscopy prior to and 1, 5, 15, 30, and 60 minutes after the administration of the experimental solutions. According to our findings, VEGF dose-dependently increased the venular diameter compared to saline. ZM323881 alone did not cause any alteration. Premedication with ZM323881 or L-NAME decreased the dilatory effects of VEGF. Occassionally moderate VEGFR2 immunohistochemical labeling was observed in the wall components of the venules. Concluding our results we can say, that there is no remarkable VEGF production under physiologic circumstances in rat gingiva, but VEGF is able to increase gingival blood flow through the activation of VEGF2 receptors and consequent NO release.

Background: Transgenic mosquito strains are being developed to contribute to the control of dengue and malaria transmission. One approach uses genetic manipulation to confer conditional, female-specific dominant lethality phenotypes. Engineering of a female-specific flightless phenotype provides a sexing mechanism essential for male-only mosquito, release approaches that result in population suppression of target vector species., Methods: An approach that uses a female-specific gene promoter and antibiotic-repressible lethal factor to produce a sex-specific flightless phenotype was adapted to the human malaria vector, Anopheles stephensi. Transposon- and site-specific recombination-mediated technologies were used to generate a number of transgenic An. stephensi lines that when combined through mating produced the phenotype of flight-inhibited females and flight-capable males., Results: The data shown here demonstrate the successful engineering of a female-specific flightless phenotype in a malaria vector. The flightless phenotype was repressible by the addition of tetracycline to the larval diet. This conditional phenotype allows the rearing of the strains under routine laboratory conditions. The minimal level of tetracycline that rescues the flightless phenotype is higher than that found as an environmental contaminant in circumstances where there is intensive use of antibiotics., Conclusions: These studies support the further development of flightless female technology for applications in malaria control programmes that target the vectors.

The epidemiology of chronic obstructive pulmonary disease (COPD) in critically ill patients is largely unknown. The aims of the study were: 1) to determine whether COPD, either as the cause of intensive care unit (ICU) admission or as a comorbid condition, is an independent risk factor for increased morbidity and mortality; and 2) to investigate time trends in proportion and outcome of acute respiratory failure in patients with COPD admitted to ICUs. Prospectively recorded data from 194 453 adults consecutively admitted to 87 Austrian ICUs over a period of 11 years (1998-2008) were retrospectively analysed. COPD was present in 8.6% of all patients. The risk-adjusted mortality of patients with COPD was higher than in patients without COPD. The presence of COPD was an independent risk factor for increased mortality and was associated with prolonged mechanical ventilation and prolonged weaning. During the course of the 11 years, the proportion of acute respiratory failure due to COPD increased by about two-thirds, and the use of noninvasive ventilation within the COPD cohort more than doubled. Simultaneously, the risk-adjusted mortality of patients with COPD improved. In critically ill patients, the presence of COPD is increasing and is an independent risk factor for mortality and morbidity.

Purpose: Changes in electrolyte homeostasis are important causes of acid-base disorders. While the effects of chloride are well studied, only little is known of the potential contributions of sodium to metabolic acid-base state. Thus, we investigated the effects of intensive care unit (ICU)-acquired hypernatremia on acid-base state., Methods: We included critically ill patients who developed hypernatremia, defined as a serum sodium concentration exceeding 149 mmol/L, after ICU admission in this retrospective study. Data on electrolyte and acid-base state in all included patients were gathered in order to analyze the effects of hypernatremia on metabolic acid-base state by use of the physical-chemical approach., Results: A total of 51 patients were included in the study. The time of rising serum sodium and hypernatremia was accompanied by metabolic alkalosis. A transient increase in total base excess (standard base excess from 0.1 to 5.5 mmol/L) paralleled by a transient increase in the base excess due to sodium (base excess sodium from 0.7 to 4.1 mmol/L) could be observed. The other determinants of metabolic acid-base state remained stable. The increase in base excess was accompanied by a slight increase in overall pH (from 7.392 to 7.429, standard base excess from 0.1 to 5.5 mmol/L)., Conclusions: Hypernatremia is accompanied by metabolic alkalosis and an increase in pH. Given the high prevalence of hypernatremia, especially in critically ill patients, hypernatremic alkalosis should be part of the differential diagnosis of metabolic acid-base disorders.

Purpose: To determine patient satisfaction and preference for implant-supported mandibular overdentures (IOD) retained with ball or Locator attachments. In addition, peri-implant conditions and prosthodontic maintenance efforts for the final attachments were evaluated after 1 year of function., Material and Methods: In this crossover clinical trial, 20 edentulous patients were recruited to receive two mandibular implants in the canine region and were provided with implant-retained mandibular overdentures and new complete maxillary dentures. Implant-retained mandibular overdentures were stabilized with either ball attachments or Locator attachments, in random order. After 3 months of function, the attachments in the existing denture were changed. Questionnaires on satisfaction/complaints with the prostheses were administered at baseline (with the old dentures) and after 3 months of function with each attachment, thus providing for an intraindividual comparison. The decision for the final attachment chosen was based on the patient's preference. For the definitive attachment, peri-implant conditions (peri-implant marginal bone resorption, pocket depth, and Plaque Index, Gingival Index, and Bleeding Index) as well as prosthodontic maintenance efforts and satisfaction score were evaluated after an insertion period of 1 year., Results: Nineteen (95%) patients completed the study (1 dropout). Patient satisfaction improved significantly (P<.05) from baseline (old dentures) to the new prostheses retained with each of the two attachment types for all domains of satisfaction. However, there were no differences between ball or Locator attachment for any items of satisfaction evaluated and neither attachment had a significant patient preference. No differences for peri-implant parameters or for patient satisfaction were noted between the definitive attachments (ball, n=10; Locator, n=9) after 1 year. Although the overall incidence rate of prosthodontic maintenance did not significantly differ between both retention modalities, the Locator attachment required more postinsertion aftercare (activation of retention) than the ball anchors.

Abutment manipulation, namely repeated screwing and unscrewing may have an affect on the final marginal bone level, consequently, soft tissue position around endosseous implants. In order to maintain the crestal bone level constant and avoid the apical recession of gingiva final abutment (Direct Abutment, Astra Tech) has been connected to submerged OsseoSpeed 4.5 dental implant (Astra Tech) in position of tooth 14, immediately after second surgical exposure. Following a healing period of three weeks, impression was taken using closed tray system and plastic impression pic-up for laboratory manufacturing of zirconium crown restoration. The functional and aesthetic result of the reconstruction was highly met patient is the satisfaction. The maintenance of marginal bone level and the excellent health of the peri-implant tissues, as registered at 6-month recall, may support the benefit of the idea of final abutment insertion immediately after one-, or two-stage surgery.

The current study measured ion release among large-head metal-on-metal hip bearings. Twenty-six patients with a modular, Profemur® TL with A-Class® big femoral head total hip replacement were matched (gender, femoral size, BMI) with a group of 26 patients with the Conserve® Plus implant hip resurfacing. Compared with HR patients, THR patients had higher median serum cobalt ion levels at 6 months (3.26 vs 1.12 μg/L, P = .002) 1 year (4.51 vs 1.02, P = .002), and 2 years (3.77 vs 1.22, P<.001) following surgery. No differences in chromium ions were observed. Further research is required to determine the clinical significance of elevated serum cobalt ions., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Introduction: The effects of three different decontaminating solutions in clinical use for peri-implantitis therapy on the chemical structure and surface roughness of commercially pure (CP) Ti were investigated. A further aim was to survey the response of the biological environment to these changes, by examining the attachment and proliferation of human epithelial cells after treatment of the Ti surfaces with these solutions., Materials and Methods: CP (grade 4) machined titanium discs (CAMLOG Biotechnologies AG, Switzerland) were treated with 3% H2O2 (5 min), saturated citric acid (pH = 1; 1 min) or chlorhexidine gel (CHX, 5 min). The surface properties were followed through the use of X-ray photoelectron spectroscopy (XPS) and atomic force microscopy (AFM). The epithelial cell attachment and proliferation was examined by means of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and bicinchoninic acid (BCA) protein-content assays., Results: XPS showed an intact TiO2 layer on each sample and CHX was adsorbed by the surface, as C-O and/or C=O bond formation was revealed. AFM results gave no significant changes in the roughness after treating the surfaces with the cleaning solutions. While MTT and BCA assays did not show significant differences in epithelial cell attachments, the cell proliferation was significantly increased after H2O2 treatment as compared to CHX (not shown by BCA assays)., Conclusions: The applied decontaminating agents do not damage the Ti surface. H2O2 can be used effectively in decontaminating the implants affected by peri-implantitis, as the human epithelial cell growth was improved, in contrast with CHX.

Background: Renal function is a major predictor of vascular function and cardiovascular diseases. Little information exists about the effect of specific renal diseases on vascular function in chronic kidney diseases (CKD)., Methods: One hundred and twenty patients (60 with IgA nephropathy, IgAN, and 60 with polycystic kidney disease, PKD) with CKD stages 1-4 were studied and compared. Pulse-wave velocity was measured by the digital volume pulse (DVP) method and stiffness index (SI(DVP)) was derived., Results: All CKD (IgAN and PKD) patients had increased SI(DVP) compared to controls (10.39 vs. 8.87 ± 1.79 m/s, p = 0.008). PKD patients had increased SI(DVP) compared to IgAN and controls (11.14 ± 2.19, 9.66 ± 2.02 and 8.87 ± 1.79 m/s, respectively, p < 0.001). An inverse correlation was found between SI(DVP) and glomerular filtration rate in all CKD (IgAN and PKD) patients (p = 0.001) and in IgAN alone (p < 0.01), but not in PKD. With multivariate regression analysis, only age and 24-hour systolic blood pressure exerted independent effects on SI(DVP)., Conclusions: Compared to controls, arterial stiffness was increased in CKD patients. However, arterial stiffening was more pronounced in PKD than in IgAN, suggesting that vascular function is not similarly altered in etiologically different CKD groups. The fact that blood pressure was an independent risk factor underscores a therapeutic opportunity., (Copyright © 2011 S. Karger AG, Basel.)

Background: Although injury to the lateral femoral cutaneous nerve (LFCN) is a known complication of anterior approaches to the hip and pelvis, no study has quantified its' incidence in anterior arthroplasty procedures., Questions/purposes: We therefore defined the incidence, functional impact, and natural history of LFCN neuropraxia after an anterior approach for both hip resurfacing (HR) and primary total hip arthroplasty (THA)., Methods: We followed 132 patients who underwent an anterior hip approach (55 THA; 77 HR). We administered self-reported questionnaires for sensory deficits of LFCN, neuropathic pain score (DN4), visual analog scale, as well as SF-12, UCLA, and WOMAC scores at one year postoperatively. A subset of 60 patients (30 THA; 30 HR) was evaluated at two time intervals., Results: One hundred seven patients (81%) reported LFCN neuropraxia with a mean severity score of 2.32/10 and a mean DN4 score of 2.42/10. Hip resurfacing had a higher incidence of neuropraxia as compared with THA: 91% versus 67%, respectively. No functional limitations were reported on SF-12, WOMAC, or UCLA scores. Of the subset of 60 patients followed over an average of 12 months, 53 (88%) reported neuropraxia at the first followup interval with only three (6%) having complete resolution at second followup. Improvement in DN4 scores was observed over time: 3.6 versus 2.5, respectively., Conclusions: Although LFCN neuropraxia was a frequent complication after anterior approach THA, it did not lead to functional limitations in our patients. A decrease in symptoms occurred over time but only a small number of patients reported complete resolution., Level of Evidence: Level III, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.

The treatment of peri-implantitis, which causes tissue deterioration surrounding osseointegrated implants, involves surface decontamination and cleaning. However, chemical cleaning agents may alter the structure of implant surfaces. We investigated three such cleaning solutions. Commercially pure (grade 4) machined titanium discs (CAMLOG Biotechnologies AG, Switzerland) were treated with 3% H(2)O(2) (5 min), saturated citric acid (pH = 1) (1 min) or chlorhexidine gel (5 min), and their surface properties were examined by atomic force microscopy (AFM) and X-ray photoelectron spectroscopy (XPS). Human epithelial cell attachment (24-h observation) and proliferation (72-h observation) were investigated via dimethylthiazolyl-diphenyltetrazolium bromide (MTT) and bicinchoninic acid (BCA) protein content assays. AFM revealed no significant difference in roughness of the three treated surfaces. XPS confirmed the constant presence of typical surface elements and an intact TiO(2) layer on each surface. The XPS peaks after chlorhexidine gel treatment demonstrated C-O and/or C=O bond formation, due to chlorhexidine digluconate infiltrating the surface. MTT and BCA assays indicated similar epithelial cell attachments in the three groups; epithelial cell proliferation being significantly higher after H(2)O(2) than after chlorhexidine gel treatment (not shown by BCA assays). These agents do not harm the Ti surface. Cleaning with H(2)O(2) slightly enhances human epithelial cell growth, in contrast to chlorhexidine gel., ((c) 2010 Wiley Periodicals, Inc.)

Stutter products are a common artifact in the PCR amplification of frequently used genetic markers that contain mononucleotide simple sequence repeats. Despite the importance of accurate determination of nucleotide sequence and allele size, there has been little progress toward decreasing the formation of stutter products during PCR. In this study, we tested the effects of lowered extension temperatures, inclusion of co-solutes in PCR, PCR cycle number, and the use of different polymerases on sequence quality for a set of sequences containing mononucleotide A/T repeats of 10-17 bp. Our analyses showed that sequence quality of mononucleotide repeats

Vertigo is one of the most common symptom and complaint in the clinical practice. The differential diagnosis can only be attained by a careful interdisciplinary way of thinking and activity, given the fact that the vestibular, neurological and psychiatric disorders--considered as pathogenic factors--are being present simultaneously in triggering the symptoms, and there can be overlaps between the certain pathological processes. The author deals with the co-morbidity of the vertigo and the psychiatric symptoms--anxiety, panic-disorder--, pointing out the common neurobiological and neurophysiological factors in the background of the symptoms, emphasizing the importance of the SSRI-s in the restoration of the serotonerg dysfunction.

Unlabelled: Metal-on-metal hip resurfacing is offered as an alternative to traditional THA for the young and active adult with advanced osteoarthritis. However, patients undergoing hip resurfacing may be predisposed to persistent groin pain due to insufficient head/neck offset, an uncovered acetabular component, or both. We therefore determined the incidence of groin pain after metal-on-metal hip resurfacing, its impact on patient function, and possible risk factors contributing to groin pain. We evaluated 116 patients with a followup of at least 12 months after surgery (mean, 26 months; range, 12-61 months). The mean age was 48.8 years (range, 24.0-66.3 years), with 21 women (18%) and 95 men (82%). All patients were evaluated clinically and radiographically and had a Harris hip score, WOMAC, UCLA Activity Rating Scale, and the RAND-36 General Health measure; they were specifically asked if they experienced groin pain currently or since their surgery. Although all patients had functional improvements postoperatively, 21 of 116 of the patients (18%) reported groin pain; 12 of these (10% of the total) stated the pain limited their activities of daily living and 11 (10%) required medication for pain. Female patients were at greater risk of having groin pain. Of the patients with groin pain, three patients had muscle atrophy with a joint effusion on CT; one of these patients had revision surgery for the pain. Patients with metal-on-metal resurfacing may have a higher incidence of pain than those with conventional THA., Level of Evidence: Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.

The pentadecapeptide BPC 157 has been shown to have anti-inflammatory and wound healing effects on multiple target tissues and organs. The purpose of the present study was to investigate the effect of BPC 157 on inflammation and bone resorption in experimental periodontitis in rats. First the acute effect of BPC was tested on gingival blood flow by laser doppler flowmetry. Then periodontitis was produced by a silk ligature placed around the lower left first molar. Rats were treated with BPC 157 (once daily for 12 days) or vehicle. At day 13, the gingivomucosal tissues encircling the molars were removed on both sides. Inflammation was assessed by Evans blue plasma extravasation technique and by histology. Alveolar bone loss was analyzed by microCT. BPC 157 had no effect on gingivomucosal blood flow. Twelve day ligature caused a significantly increased Evans blue extravasation in the gingivomucosal tissue, histological signs of inflammation, and alveolar bone destruction. BPC 157 treatment significantly reduced both plasma extravasation, histological alterations and alveolar bone resorption. In conclusion, systemic application of BPC 157 does not alter blood circulation in healthy gingiva. Chronic application of the peptide has potent antiinflammatory effects on periodontal tissues in ligature induced periodontitis in rats. Taken together, this proof of concept study suggests that BPC 157 may represent a new peptide candidate in the treatment of periodontal disease.

Background: Endothelial cell proliferation, angiogenesis, and increased vascular permeability are among the effects of vascular endothelial growth factor (VEGF) in various organs. However, the effects of VEGF on gingival hemodynamics, especially on venules, have not been thoroughly investigated. This study investigated the acute circulatory effects of VEGF on rat gingival venules., Methods: Fifty-six anesthetized rats were divided into five study groups; each rat received 10 microl of experimental solution dripped onto the lower interincisal gingiva. The groups included: 1) saline control (after the experiment, gingiva was excised for VEGF receptor 2 [VEGFR2] immunohistochemistry); 2) VEGF (0.1, 1, 10, or 50 microg/ml); 3) VEGF2 receptor antagonist 5-((7-benzyloxyquinazolin-4-yl)amino)-4-fluoro-2-methyl-phenol-hydrochloride (ZM323881; 20 microg/ml); 4) ZM323881 (20 microg/ml) followed by VEGF application (50 microg/ml after 15 minutes); and 5) VEGF (10 microg/ml), these rats were premedicated with nitric oxide (NO) synthase blocker (N(G)-nitro-L-arginine-methyl-ester [L-NAME]; 1 mg/ml in drinking water) for 1 week before the experiment. Changes in gingival superficial venule diameter were measured by vital microscopy prior to and 1, 5, 15, 30, and 60 minutes after the administration of the experimental solutions., Results: VEGF dose-dependently increased the venular diameter compared to saline. ZM323881 alone did not cause any alteration. Premedication with ZM323881 or L-NAME decreased the dilatory effects of VEGF. VEGFR2 immunohistochemical labeling was observed in the wall of the venules., Conclusions: There is no remarkable VEGF production under physiologic circumstances in rat gingiva, but VEGF is able to increase gingival blood flow through the activation of VEGF2 receptors. Furthermore, NO release may contribute to VEGF's vasodilatory effect.

Fluoride is a reductive agent and may modify the oxide layer of titanium (Ti) in the transgingival region of dental implants. The low pH and the high fluoride concentration of prophylactic mouthwashes and gels (used in caries prevention) may play a role in this phenomenon. Our main goal was to examine whether changes on the surface structure of Ti caused by high fluoride concentration and acidic pH alter the adherence and the colonization of bacteria. Polished commercially pure Ti discs (CP grade 4, Camlog, Biotechnologies AG, Switzerland) were used in the study. Each sample was treated for 1 hour with one of the solutions: mouthwash containing 0.025% (250 ppm) fluoride, a gel containing 1.25% (12500 ppm) fluoride, and a solution of 1% NaF (3800 ppm fluoride), pH 4.5. The surface structure of the discs was analyzed by atomic force microscopy (AFM) and X-ray photoelectron spectroscopy (XPS). The colonization of Streptococcus mutans was studied by scanning electron microscope (SEM) after a 5-day incubation period. The roughness of the treated sample surfaces (Ra), as revealed by AFM measurements, increased 1.3 times for the gel and the mouthwash, and approximately seven folds for the 1% NaF solution, as compared to the control surface. The high fluoride concentration and acidic pH of the gel and the 1% NaF solution resulted in a strong corrosion and a modification of the composition of the Ti surface. The XPS spectra showed the formation of a fluoride containing complex (Na2TiF6) bound strongly to the surface. A correlation was revealed between the roughness of the surface and thickness and maturity of the S. mutans bacterial colonies developed on the modified Ti surface. High fluoride concentration and acidic pH increased the roughness of the Ti surface. Bacterial biofilm colonization on this rough surface proved to be more mature. The amount of bacteria was increased due to the changes in the surface caused by fluoride treatment. The present study indicates that high fluoride concentration in an acidic pH environment may affect the development of a healthy transgingival epithelial junction on the Ti surface. This work was supported by the SIMI-NAS Project of the 5th FWP of the European Commission (Growth Program, GRD3-2001-61801), the Hungarian Ministry of Economy and the EC (GVOP-3.2.1.-2004-04-0408/3.0), the Hungarian Ministry of Health (ETT, 434/2006), and the Hungarian Scientific Research Fund (OTKA F-68440).

High fluoride (F(-)) concentrations and acidic pH impair the corrosion resistance of titanium (Ti). Effects of F(-)-containing caries-preventive prophylactic rinses, and gels on Ti were investigated by X-ray photoelectron spectroscopy (XPS) and atomic force microscopy (AFM). Human epithelial cell attachment and proliferation were investigated by dimethylthiazol-diphenyl tetrazolium bromide (MTT) and protein content assays. Aqueous 1% NaF solution (3800 ppm F(-), pH 4.5) or high (12,500 ppm) F(-) content gel (pH 4.8) strongly corroded the surface and modified its composition. XPS revealed formation of a strongly bound F(-)-containing complex (Na(2)TiF(6)). AFM indicated an increase in roughness (R(a)) of the surfaces: 10-fold for the NaF solution and smaller for the gel or a mouthwash (250 ppm F(-), pH 4.4). MTT revealed that cell attachment was significantly increased by the gel, but was not disturbed by either the mouthwash or the NaF. Cell proliferation determined by MTT decreased significantly only for the NaF-treated samples; protein content assay experiments showed no such effect. This study indicates that epithelial cell culturing results can depend on the method used, and the adverse effects of a high F(-) concentration and low pH should be considered when prophylactic gels are applied by patients with Ti implants or other dental devices.

Peripheral and central vestibular syndromes are characterized by the combination of the four symptoms such as: vertigo, nystagmus, imbalance and nausea. Vertigo is the disturbance of the cortico-spatial orientation. Nystagmus is regarded as a secondary symptom caused by direction specific disequilibrium of the vestibulo-ocular reflex. Imbalance is caused by the abnormal activation of vestibulo-spinal pathways. Nausea is due to the activation of the medullary vomiting center. It is important that clinicians can establish an adequate diagnosis and differentiate vertigo and dizziness. The author--without the aim of completeness--discusses the types of vertigo caused by the most important disorders of the central nervous system, emphasizing the role of general practitioners in the diagnostic and therapeutic algorhytm.