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Focuses on the impact of receding groundwater levels and atmospheric deposition on biodiversity of Dutch forests. Increase of drought tolerant species in the forests; Adverse effects of desiccation; Disruption of nutrient balance of trees.

Studies have been carried out in two fully stocked, fast growing Douglas-fir plantations of the Dutch ACIFORN project in three consecutive years, to obtain information on fine root densities (Olsthoorn 1991). For the present paper, data collected in early summer 1987 were used to study the relation of fine root density and proximity to the nearest tree or the dominant tree. A large number of samples (37 in onesite and 55 in another) was collected in a small plot (10 x 11 m). Two distances were measured at each sampling point: the distance to the nearest tree and the distance to the tree with a dominant crown above that point. There was large variability in fine root density in the samples. Tests with different regression models showed a distinct rooting pattern for one of the two locations. It is concluded that systematic errors in the assessment of fine root density can arise when sampling points are chosen at a constant distance from trees. For Douglas-fir, this systematic error could have been an overestimation of the fine root density by up to 10%. These systematic errors can be avoided easily, using a stratified random design or a random sampling design. When trees are spaced irregularly, a grid sampling design is also appropriate. [ABSTRACT FROM AUTHOR]

Objective: This study's purpose was to determine if the learning environment impacts student anxiety in a dental hygiene program by evaluating the two main learning environments: the dental clinic and the traditional classroom. This study also examined educational tasks and their association with anxiety in each learning environment., Methods: A web-based survey was conducted using a convenience sample of dental hygiene students enrolled in a two or four year CODA-accredited dental hygiene program in the United States. The Beck Anxiety Inventory was used to determine each participant's anxiety levels in both learning environments. Data analysis included descriptive statistics, correlation, and an analysis of variance., Results: According to the Beck Anxiety Inventory scoring, dental hygiene students experience a moderate level of anxiety when learning in the dental clinic and a low level of anxiety when learning in the classroom. Nervousness was the most reported anxiety symptom in both the dental clinic and the traditional classroom. Test results from the Spearman correlation show that all dental clinic and classroom educational tasks have a significant correlation (p < 0.01) to a student's anxiety level. Anxiety reported by students did not statistically differ by the year in which they were in the dental hygiene program., Conclusion: Findings suggest anxiety does exist at a moderate level in dental hygiene students. The dental clinic learning environment is associated with greater anxiety among dental hygiene students. Results from this study will be beneficial in understanding how to facilitate student success in a dental hygiene program., (© 2024 The Author(s). Journal of Dental Education published by Wiley Periodicals LLC on behalf of American Dental Education Association.)

Objectives: Transcutaneous posterior tibial nerve stimulation (TC-PTNS) is a validated option for lower urinary tract symptoms (LUTS) management, with a short-term success rate of around 60% and few adverse events. Our goal was to report the efficacy and safety results of TC-PTNS using the newly issued device TENSI+ for LUTS management., Patients and Methods: A multicenter, retrospective study was conducted in 7 urology departments in France. All patients treated with TC-PTNS for LUTS using the TENSI+ device between September 2021 and February 2022 were included. All patients received supervised at-home training by a specialized nurse. All patients were asked to do daily, 20minutes sessions of TC-PTNS. Patient demographics, history, initial symptoms and previous treatment were collected at inclusion. A follow-up visit was scheduled at 3 months. Efficacy was evaluated through treatment persistence at 3 months and PGI-I (Patient Global Impression of Improvement) score. Adverse events were recorded., Results: One hundred and three patients (86 women and 17 men) were included. All patients had overactive bladder symptoms, 64 suffered from urgency incontinence, and 24 had associated voiding symptoms. Eighteen patients had neurogenic background, and 30 previously received anticholinergics. After a median follow-up of 12 [10-21]weeks, 70 patients were still using the device (68%). PGI-I score reflected an improvement in 70.9% and was 1, 2 and 3 in 28, 26 and 19 patients respectively, while 24 were unchanged and 6 were worse. No clinical baseline parameter was predictive of success. Adverse events included pain at stimulation site (two cases) and pelvic pain (two patients), which rapidly resolved after treatment interruption., Conclusions: TC-PTNS with TENSI+ device is an effective option for LUTS management, with results that seem similar to other TC-PTNS approaches. Adverse events were mild and reversible after treatment interruption., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Introduction: Multidisciplinary team meetings (MTMs) in the field of pelvic floor diseases in women tend to generalize, as they are required as mandatory before mid-urethral sling implantation or sacrocolpopexy by recent decrees published by the French health authorities. However, access to these meetings is variable in the French territory. The goal of the present study was to describe the existence and the settings of these kinds of meetings in France., Materiel and Methods: An on-line survey was conducted between June and July 2020 (stage 1) then between November 2021 and January 2022 (stage 2). A 15-item questionnaire was sent to all members of the Association française d'urologie (AFU). A descriptive analysis was conducted., Results: Three hundred and twenty-two completed questionnaires were sent back during stage 1 and 158 during stage 2. Early 2022, 61.3% of respondents had access to a pelviperineology MTM, with important difference according to geographical areas. Main activity of MTMs was case discussion of complex situations (68% of meetings). At the end of 2021, 22% of the respondents declared willing to stop partially or totally their pelviperineology activity, given the new regulations set in place by the authorities., Conclusion: Despite being absolutely mandatory in current clinical practice, MTMs in pelvic floor disease have spread slowly. MTMs implementation was still insufficient in 2022, and variable on the French territory. Some urologists declare having no access to such resources and about 1 out of 5 were considering to voluntary stop of decrease significantly their activity in this difficult context., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Background and Objectives: successful interventions to prevent cerebrovascular disease and stroke require early identification of persons at risk before clinical manifestation of disease. The literature remains to be sparse on accessible plasma-based biomarkers for monitoring brain health and cerebrovascular disease in advanced age. We assessed the predictive value of biological age (BA) as an early indicator for cerebrovascular disease and risk of first-ever intracerebral hemorrhage (ICH) and cerebral infarction (CI) in advanced age and compared these relationships with chronological age (CA) and commonly used biomarkers including tau and Aβ40 and Aβ42., Methods: The study included Individuals who consented for blood draw and follow-up. We computed biological age using structural equation modelling. The criteria for the biomarkers included their representability of the various body systems; their availability in the Rotterdam study and their pre-hypothesized reflection of aging in other populations. The algorithm integrates biomarkers that represent six body systems involved in overall cerebrovascular health including metabolic function, cardiac function, lung function, kidney function, liver function, immunity, and inflammation. Time to event analysis was conducted using Cox-regression models. Prediction analysis was conducted using Harrel's C and Area under the receiver operating characteristic curve., Results: The sample included a total of 1699 individuals at baseline followed up over a median of 11 years. During a period of 15, 780 and 16, 172 person-years, a total of 17 first-ever intracerebral hemorrhage and 83 cerebral infarction cases occurred. In time-to-event analysis, BA showed higher magnitude of associations with ICH compared to CA (HR BA-ICH: 2.30, 95% CI: 1.20, 4.30; HR CA-ICH: 1.40, 95% CI: 0.76, 2.53) and higher precision with CI (HR BA-CI: 1.30, 95% CI: 1.01,1.75; HR CA-CI: 1.90, 95% CI: 1.48, 2.66). BA outperformed CA for prediction of ICH (AUC: 0.68 vs 0.53; Harrel's C: 0.72 vs 0.53) and for CI (AUC:0.63 vs 0.62; Harrel's C: 0.68 vs 0.67)., Conclusions: Biological aging (delta biological aging) based on integrated physiology biomarkers provides a novel tool for monitoring and identification of persons at highest risk of cerebrovascular disease in advanced age with varying degrees of precision and magnitude for stroke subtypes. These variations are likely related to differences in pathophysiology of intracerebral hemorrhage and cerebral infarction. Wider validation and applicability require extension of these findings in other comparable samples and in clinical settings., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

CSF biomarkers, including total-tau, neurofilament light chain (NfL) and amyloid-β, are increasingly being used to define and stage Alzheimer's disease. These biomarkers can be measured more quickly and less invasively in plasma and may provide important information for early diagnosis of Alzheimer's disease. We used stored plasma samples and clinical data obtained from 4444 non-demented participants in the Rotterdam study at baseline (between 2002 and 2005) and during follow-up until January 2016. Plasma concentrations of total-tau, NfL, amyloid-β40 and amyloid-β42 were measured using the Simoa NF-light® and N3PA assays. Associations between biomarker plasma levels and incident all-cause and Alzheimer's disease dementia during follow-up were assessed using Cox proportional-hazard regression models adjusted for age, sex, education, cardiovascular risk factors and APOE ε4 status. Moreover, biomarker plasma levels and rates of change over time of participants who developed Alzheimer's disease dementia during follow-up were compared with age and sex-matched dementia-free control subjects. During up to 14 years follow-up, 549 participants developed dementia, including 374 cases with Alzheimer's disease dementia. A log2 higher baseline amyloid-β42 plasma level was associated with a lower risk of developing all-cause or Alzheimer's disease dementia, adjusted hazard ratio (HR) 0.61 [95% confidence interval (CI), 0.47-0.78; P < 0.0001] and 0.59 (95% CI, 0.43-0.79; P = 0.0006), respectively. Conversely, a log2 higher baseline plasma NfL level was associated with a higher risk of all-cause dementia [adjusted HR 1.59 (95% CI, 1.38-1.83); P < 0.0001] or Alzheimer's disease [adjusted HR 1.50 (95% CI, 1.26-1.78); P < 0.0001]. Combining the lowest quartile group of amyloid-β42 with the highest of NfL resulted in a stronger association with all-cause dementia [adjusted HR 9.5 (95% CI, 2.3-40.4); P < 0.002] and with Alzheimer's disease [adjusted HR 15.7 (95% CI, 2.1-117.4); P < 0.0001], compared to the highest quartile group of amyloid-β42 and lowest of NfL. Total-tau and amyloid-β40 levels were not associated with all-cause or Alzheimer's disease dementia risk. Trajectory analyses of biomarkers revealed that mean NfL plasma levels increased 3.4 times faster in participants who developed Alzheimer's disease compared to those who remained dementia-free (P < 0.0001), plasma values for cases diverged from controls 9.6 years before Alzheimer's disease diagnosis. Amyloid-β42 levels began to decrease in Alzheimer's disease cases a few years before diagnosis, although the decline did not reach significance compared to dementia-free participants. In conclusion, our study shows that low amyloid-β42 and high NfL plasma levels are each independently and in combination strongly associated with risk of all-cause and Alzheimer's disease dementia. These data indicate that plasma NfL and amyloid-β42 levels can be used to assess the risk of developing dementia in a non-demented population. Plasma NfL levels, although not specific, may also be useful in monitoring progression of Alzheimer's disease dementia., (© The Author(s) (2020). Published by Oxford University Press on behalf of the Guarantors of Brain.)

MicroRNAs (miRNAs) are non-coding RNA molecules that regulate gene expression. Extensive research has explored the role of miRNAs in the risk for type 2 diabetes (T2D) and coronary heart disease (CHD) using single-omics data, but much less by leveraging population-based omics data. Here we aimed to conduct a multi-omics analysis to identify miRNAs associated with cardiometabolic risk factors and diseases. First, we used publicly available summary statistics from large-scale genome-wide association studies to find genetic variants in miRNA-related sequences associated with various cardiometabolic traits, including lipid and obesity-related traits, glycemic indices, blood pressure, and disease prevalence of T2D and CHD. Then, we used DNA methylation and miRNA expression data from participants of the Rotterdam Study to further investigate the link between associated miRNAs and cardiometabolic traits. After correcting for multiple testing, 180 genetic variants annotated to 67 independent miRNAs were associated with the studied traits. Alterations in DNA methylation levels of CpG sites annotated to 38 of these miRNAs were associated with the same trait(s). Moreover, we found that plasma expression levels of 8 of the 67 identified miRNAs were also associated with the same trait. Integrating the results of different omics data showed miR-10b-5p, miR-148a-3p, miR-125b-5p, and miR-100-5p to be strongly linked to lipid traits. Collectively, our multi-omics analysis revealed multiple miRNAs that could be considered as potential biomarkers for early diagnosis and progression of cardiometabolic diseases., (Copyright © 2020 Mens, Maas, Klap, Weverling, Klatser, Brakenhoff, van Meurs, Uitterlinden, Ikram, Kavousi and Ghanbari.)

Chronological age alone is not a sufficient measure of the true physiological state of the body. The aims of the present study were to: (1) quantify biological age based on a physiological biomarker composite model; (2) and evaluate its association with death and age-related disease onset in the setting of an elderly population. Using structural equation modeling we computed biological age for 1699 individuals recruited from the first and second waves of the Rotterdam study. The algorithm included nine physiological parameters (c-reactive protein, creatinine, albumin, total cholesterol, cytomegalovirus optical density, urea nitrogen, alkaline phosphatase, forced expiratory volume and systolic blood pressure). We assessed the association between biological age, all-cause mortality, all-cause morbidity and specific age-related diseases over a median follow-up of 11 years. Biological age, compared to chronological age or the traditional biomarkers of age-related diseases, showed a stronger association with all-cause mortality (HR 1.15 vs. 1.13 and 1.10), all-cause morbidity (HR 1.06 vs. 1.05 and 1.03), stroke (HR 1.17 vs. 1.08 and 1.04), cancer (HR 1.07 vs. 1.04 and 1.02) and diabetes mellitus (HR 1.12 vs. 1.01 and 0.98). Individuals who were biologically younger exhibited a healthier life-style as reflected in their lower BMI (P < 0.001) and lower incidence of stroke (P < 0.001), cancer (P < 0.01) and diabetes mellitus (P = 0.02). Collectively, our findings suggest that biological age based on the biomarker composite model of nine physiological parameters is a useful construct to assess individuals 65 years and older at increased risk for specific age-related diseases.

Background and Objective: To evaluate risk factors and complications of retroperitoneoscopic procedures of upper urinary tract and adrenal gland., Methods: From 1994 to 2016, 1,000 retroperitoneal laparoscopies were performed - 476 nephrectomies, 201 adrenalectomies, 103 partial nephrectomies, 91 pyeloplasties, 70 nephro-ureterectomies, and 59 miscellaneous surgeries (diverticulectomy). Data collection was prospective. We analyzed age, body mass index (BMI), American Society of Anesthesiologists (ASA) score, operative time, blood loss, hospitalization stay and complications. Risks factors were explored with univariate and multivariate analysis., Results: The mean BMI was 25 and median ASA 2. The mean operative time was 136 mn, mean blood loss 149 mL. There were 49 conversions. Of the patients, 41 required re-interventions, predominantly due to urinary fistula or post-operative bleeding. Post-operatively, 145 complications were recorded. In multivariate analysis, partial nephrectomies (OR 2.12, p = 0.031, 95% CI [1.07-4.22]) and pyeloplasties (OR 1.97, p = 0.02, 95% CI [1.11-3.48]) were significantly more at risk of complication than nephrectomies. An ASA score of 3 was also a significant risk factor of complications (OR 2.3, p = 0.014, 95% CI [1.17-4.47]) and an increased BMI carried a higher risk of conversion. There was no significant difference of conversion or complication rates between the first and last 500 patients., Conclusions: Upper urinary tract and adrenal surgeries can be performed by retroperitoneal laparoscopy. This surgical technic is safe and reproducible. The choice of the technic must be oriented by ASA, BMI and the type of surgery., (© 2019 S. Karger AG, Basel.)

Background: Various studies have shown that infants under the age of 6 months are especially vulnerable for complications due to influenza. Currently there are no vaccines licensed for use in this age group. Vaccination of pregnant women during the last trimester, recommended by the WHO as protective measure for this vulnerable female population, may provide protection of newborns at this early age. Although it has been observed that maternal vaccination can passively transfer protection, maternal antibodies could possibly also interfere with subsequent active vaccination of the offspring., Methods: Using a mouse model, we evaluated in depth the ability of maternal influenza vaccination to protect offspring and the effect of maternal immunization on the subsequent influenza vaccination of the offspring. By varying the regimen of maternal immunization we explored the impact of different levels of maternal antibodies on the longevity of these antibodies in their progeny. We subsequently assessed to what extent maternal antibodies can mediate direct protection against influenza in their offspring, and whether these antibodies interfere with protection induced by active vaccination of the offspring., Results: The number of immunizations of pregnant mice correlates to the level and longevity of maternal antibodies in the offspring. When these antibodies are present at time of influenza challenge they protect offspring against lethal influenza challenge, even in the absence of detectable HAI titers. Moreover, no detectable interference of passively-transferred maternal antibodies on the subsequent vaccination of the offspring was observed., Conclusion: In the absence of a licensed influenza vaccine for young children, vaccination of pregnant women is a promising measure to provide protection of young infants against severe influenza infection.

Penile cancer is a rare malignancy, which can be a source of devastating psychosexual distress because of its implication on sexual function and self-image. Current penile staging relies on invasive techniques and is often inaccurate. The authors review the promising biomarkers currently under investigation and their application to the staging and prognosis of penile cancer. Further development of such biomarkers provides the potential of improved clinical management of this disease., (Published by Elsevier Inc.)

Purpose: For many years it was believed that higher total testosterone contributed to prostate cancer and caused rapid cancer growth. International guidelines consider that adequate data are not available to determine whether there is additional risk of prostate cancer from testosterone replacement. Numerous studies with multiple designs and contradictory conclusions have investigated the relationship between total testosterone and prostate cancer development. To establish current knowledge in this field we reviewed the literature on total testosterone and the subsequent risk of prostate cancer as well as the safety of exogenous testosterone administration in patients with a history of prostate cancer., Materials and Methods: We searched the literature to identify articles from 1994 to 2014 related to the relationship between total testosterone and prostate cancer. Emphasis was given to prospective studies, series with observational data and randomized, controlled trials. Case reports were excluded. Articles on testosterone replacement safety were selected by patient population (under active surveillance or with a prostate cancer history). We organized our results according to the relationship between total testosterone and prostate cancer, including 1) the possible link between low total testosterone and prostate cancer, 2) the effect of high levels and 3) the absence of any link. Finally, we summarized studies of the risk of exogenous testosterone administration in patients already diagnosed with prostate cancer, treated or on active surveillance., Results: We selected 45 articles of the relationship between total testosterone and prostate cancer, of which 18 and 17 showed a relationship to low and high total testosterone, respectively, and 10 showed no relation. Total testosterone was defined according to the definition in each article. Contradictory findings have been reported, largely due to the disparate methodologies used in many studies. Most studies did not adhere to professional society guidelines on total testosterone measurements. One of 18 series of low total testosterone and prostate cancer adhered to published guidelines while none of 17 showing a relationship of high total testosterone to prostate cancer and only 1 of 10 that identified no relationship between total testosterone and prostate cancer adhered to measurements recommended in the guidelines. In 11 studies the risk of exogenous testosterone was examined in patients with a prostate cancer history. Many studies were limited by small cohort size and brief followup. However, overall this literature suggests that the risk of exogenous testosterone replacement in patients with prostate cancer appears to be small., Conclusions: The relationship between total testosterone and prostate cancer has been an area of interest among physicians for decades. Conflicting results have been reported on the relationship between total testosterone and subsequent prostate cancer. Much of this controversy appears to be based on conflicting study designs, definitions and methodologies. To date no prospective study with sufficient power has been published to unequivocally resolve the issue. The preponderance of studies of the safety of exogenous testosterone in men with a prostate cancer history suggests that there is little if any risk. However, because the risk has not proved to be zero, the most prudent course is to follow such men with regular prostate specific antigen measurements and digital rectal examinations., (Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Objectives: To evaluate baseline renal dysfunction among patients undergoing urological oncological surgery and its impact on early postoperative outcomes., Methods: Between 2005 and 2011, patients who underwent minimally-invasive or open radical prostatectomy, partial nephrectomy and radical nephrectomy, or open radical cystectomy, respectively, were identified in the National Surgical Quality Improvement Program dataset. Preoperative kidney function was assessed using estimated glomerular filtration rate and staged according to National Kidney Foundation definitions. Multivariable logistic regression was used to model the association between preoperative renal function and the risk of 30-day mortality and major complications. Furthermore the impact of chronic kidney disease on operation time and length of hospital stay was assessed., Results: Overall, 13,168 patients underwent radical prostatectomy (65.4%), partial nephrectomy (10.7%) and radical nephrectomy (16.1%) and radical cystectomy (7.8%), respectively; 50.1% of evaluable patients had reduced kidney function (chronic kidney disease II), and a further 12.6, 0.7 and 0.9% were respectively classified into chronic kidney disease stages III, IV, and V. Chronic kidney disease was an independent predictor of 30-day major postoperative complications (chronic kidney disease III: odds ratio 1.61, P < 0.001; chronic kidney disease IV: odds ratio 2.24, P = 0.01), of transfusions (chronic kidney disease III: odds ratio 2.14, P < 0001), of prolonged length of stay (chronic kidney disease III: odds ratio 2.61, P < 0.001; chronic kidney disease IV: odds ratio 3.37, P < 0.001; and chronic kidney disease V: odds ratio 1.68; P = 0.03) and of 30-day mortality (chronic kidney disease III: odds ratio 4.15, P = 0.01; chronic kidney disease IV: odds ratio 10.10, P = 0.003; and chronic kidney disease V: odds ratio 17.07, P < 0.001) compared with patients with no kidney disease., Conclusions: Renal dysfunction might be underrecognized in patients undergoing urological cancer surgery. Chronic kidney disease stages III, IV and V are independent predictors for poor 30-day postoperative outcomes., (© 2014 The Japanese Urological Association.)

Introduction: Bacillus Calmette-Guerin (BCG) instillations are the recommended treatment for non-muscle invasive bladder cancer but high recurrence and progression rates remain after treatment. Despite patients risk stratification, BCG effectiveness remains unpredictable. A close, invasive and expensive follow up is mandatory. To improve or even replace this heavy surveillance in this high risk population, validated biomarkers were developed., Materials and Methods: To identify the useful tools for the urologist in monitoring bladder cancer patients, we reviewed the literature focusing on plasma and urinary biomarkers of BCG-therapy outcome. Articles dated from 1988 to 2013 including specific keywords (urinary bladder neoplasm, biological markers, intravesical administration, recurrence) were examined and relevant papers were selected., Results: Before treatment initiation, genetic polymorphisms of multiple agents (cytokines, matrix-metalloproteinases) were found to become very useful to tailor therapy and monitoring. Those biomarkers belong to personalized medicine which is a topic of great interest today, but still need to be validated in cohorts from different ethnicities. During instillations, cytokines (IL-2, IL-8, IL-6/IL-10) were reported to be reliable to determine treatment response and efficacy. Further studies are needed to confirm results and standardize thresholds. After treatment, UroVysion, the FDA-approved fluorescence in situ hybridization (FISH), appeared to be the most robust marker of all the clinical parameters reviewed; but is not yet validated for BCG-treated patients., Conclusions: No recommendations for everyday practice can be established today, but a combination of several markers and clinicopathological characteristics may be the future. As bladder cancer diagnosis and management are evolving, practicing urologists should be aware of and utilize bladder cancer markers in clinical practice.

Objectives: To identify predictive factors of bladder recurrence after radical nephroureterectomy and to evaluate the impact of this event on oncological outcomes., Methods: We carried out a retrospective analysis of 237 patients treated with radical nephroureterectomy for urothelial carcinoma of the upper tract at our institution from 1998 to 2011. Univariable and multivariable models evaluated the prognostic factors of bladder recurrence, and its impact on recurrence-free survival and cancer-specific survival., Results: The median age was 69.3 years (interquartile range 60-76). With a median follow up of 44 months (interquartile range 24-79), bladder recurrence occurred in 85 patients (35.9%). A previous history of bladder cancer (P = 0.01) and the presence of concomitant carcinoma in situ (P = 0.005) remained independent predictors of bladder recurrence. The presence of bladder recurrence was not correlated with worse oncological outcomes in terms of disease recurrence (P = 0.075) and cancer-specific mortality (P = 0.06). However, the patients who experienced muscle-invasive bladder cancer recurrence had worse outcomes in terms of cancer-specific mortality (P = 0.01). Standard pathological features of aggressiveness, such as higher tumor stage (P = 0.05), higher grade (P = 0.01) and carcinoma in situ (P = 0.03), were independent predictors of muscle-invasive bladder cancer recurrence., Conclusions: Previous history of bladder cancer, tumor location and concomitant carcinoma in situ are independent predictors of bladder recurrence in patients undergoing radical nephroureterectomy. Bladder recurrence overall does not impact the oncological outcomes, but a muscle-invasive bladder recurrence is associated with a worse cancer-specific mortality. Standard pathological features of urothelial carcinoma of the upper tract aggressiveness (pT-stage, grade) are independent predictors of muscle-invasive bladder cancer recurrence., (© 2013 The Japanese Urological Association.)

The avian influenza H5 virus epizootic continues to cause zoonosis with human fatalities, highlighting the continued need for pandemic preparedness against this subtype. This study evaluated the tolerability and immunogenicity of a Matrix M™ adjuvanted virosomal H5N1 vaccine in a phase I clinical trial. Sixty healthy adults were vaccinated intramuscularly with two doses of influenza H5N1 (NIBRG-14) virosomal vaccine alone (30 μg haemagglutinin (HA)) or 1.5, 7.5 or 30 μg HA formulated with 50 μg Matrix M™ adjuvant. The antibody response was analysed by haemagglutination inhibition (HI), microneutralisation (MN) and single radial haemolysis (SRH) assays. The vaccine was well tolerated in all groups but injection site pain was more frequently observed in the Matrix M™ adjuvanted groups. The vaccine elicited homologous and heterologous H5N1-specific antibody responses and the Matrix M™ adjuvanted formulations met all the EU regulatory criteria. In conclusion, Matrix M™ adjuvant was well tolerated and augmented the antibody response allowing considerable dose sparing down to 1.5 μg HA., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

A vaccine that elicits both specific antibodies and IFN-gamma-producing T cells is required to protect against pre-erythrocytic malaria. Among the most promising approaches to induce such complex immunity are heterologous prime-boost vaccination regimens, in particular ones containing live viral vector. We have demonstrated previously that adenovectors serotype 35 (Ads35) encoding the circumsporozoite (CS) antigen or liver-stage antigen-1 (LSA-1) are highly effective in improving the T-cell responses induced by immunizations with protein-based vaccines in a heterologous prime-boost schedule. Here we evaluated the potential of a heterologous prime-boost vaccination that combines the Ad35.CS vector with the serologically distinct adenovector Ad5.CS, in rhesus macaques, after establishing the potency in mice. We show that the heterologous Ad35.CS/Ad5.CS prime-boost regimen elicits both antibody responses and robust IFN-gamma-producing CD8(+) T-cell responses against the CS antigen. Analysis of the quality of the antibody responses in rhesus macaques, using indirect immunofluorescence assay (IFA) with Plasmodium falciparum-coated slides, demonstrated that this heterologous prime-boost regimen elicits a high titer of antibodies that are able to bind to P. falciparum sporozoites. Level of the IFA response was superior to the response measured with sera of an adult human population living in endemic malaria region. In conclusion, the combination of Ad35.CS, a vaccine based on a rare serotype adenovirus, with Ad5.CS or possibly another adenovector of a distinct serotype, induces a complex immune response that is required for protection against malaria, and is thus a highly promising approach for pediatric vaccination.