Search

Introduction: High grade, non-muscle invasive bladder cancer (NMIBC) is usually treated with intravesical Bacillus Calmette-Guérin. Chemohyperthermia therapy (CHT) may be a novel alternative therapy for the treatment of NMIBC., Objective: To evaluate the recurrence-free survival (RFS) of patients treated with CHT using the Combat bladder recirculation system (BRS) for NMIBC., Methods: This was a prospective multi-institutional study of 1,028 consecutive patients with NMIBC undergoing CHT between 2012 and 2020. A total of 835 patients were treated with CHT with Mitomycin C (MMC). Disease was confirmed on transurethral resection of bladder tumor (TURBT) prior to starting CHT. Follow-up included cystoscopy and subsequent TURBT if recurrence/progression was suspected. The primary endpoint was RFS. Secondary endpoints were progression-free survival (PFS) and adverse events from CHT., Results and Limitations: Median follow up was 22.4 months (Interquartile range (IQR): 12.8 -35.8). Median age was 70.4 years (IQR: 62.1 -78.6). A total of 557 (66.7%), 172 (20.6) and 74 (8.9%) of patients were classified to BCG naïve, BCG unresponsive and BCG failure, respectively. The RFS at 12 months and 24 months for BCG naïve was 87.6% (95% CI 85.0% - 90.4%) and 75.0% (95% CI 71.3% - 78.8%), respectively. The RFS at 12 months and 24 months for BCG unresponsive cohort was 78.1% (95% CI 72.0% - 84.7%) and 57.4% (95% CI 49.7% - 66.3%), respectively. The RFS at 24 months for the BCG unresponsive cohort for CIS with/without papillary disease and papillary only disease were 43.6% (95% CI 31.4% -60.4%) and 64.5% (95% CI 55.4% - 75.1%), respectively. Minor adverse events occurred in 216 (25.6%) patients and severe events occurred in 17 (2.0%) patients., Conclusions: CHT with MMC using the Combat BRS is effective in the medium term and has a favorable adverse event profile., Competing Interests: Daniel A. González-Padilla has received payment for trial collaboration from Combat Medical. Félix Guerrero Ramos is a consultant and speaker for Combat Medical. Wei Shen Tan is a consultant to Combat Medical. Joan Palou Redorta is an Editorial Board member of this journal, but was not involved in the peer-review process nor had access to any information regarding its peer-review. Wei Phin Tan, Ana Plata Bello, Carlos Garcia Alvarez, Cajetan Nzeh, Jose Manuel de la Morena, Ignacio Gonzalez Valcarcel de Torres, Kees Hendricksen, Francisco Javier Díaz Goizueta, Fernandez J. Del Alamo, Francesco Chiancone, Paolo Fedelini, Massimiliano Poggio, Francesco Porpiglia, Victoria C. Gonzalo Rodríguez, Javier Montero Torres, Daniel Wilby, Richard Robinson, Alejandro Sousa-Escandón, Juan León Mata, Jose L. Pontones Moreno, Francisco Delgado Molina, Miguel A. Adriazola Semino, Andrew Townsley Stemberger and Jesús Calleja-Escudero declare no conflicts of interest., (© 2022 – The authors. Published by IOS Press.)

Caloric restriction (CR) prolongs life span, yet the mechanisms by which it does so remain poorly understood. Under CR, mice self-impose chronic cycles of 2-hour feeding and 22-hour fasting, raising the question of if it is calories, fasting, or time of day that is the cause of this increased life span. We show here that 30% CR was sufficient to extend the life span by 10%; however, a daily fasting interval and circadian alignment of feeding acted together to extend life span by 35% in male C57BL/6J mice. These effects were independent of body weight. Aging induced widespread increases in gene expression associated with inflammation and decreases in the expression of genes encoding components of metabolic pathways in liver from ad libitum-fed mice. CR at night ameliorated these aging-related changes. Our results show that circadian interventions promote longevity and provide a perspective to further explore mechanisms of aging.

Objective: 24.1% of COVID-19 cases reported in Spain from the start of the COVID-19 alert until 29 May 2020 were in healthcare workers. The aim was to describe the demographic, clinical and epidemiological characteristics of Primary Care professionals notified for suspected or contact COVID-19 and to know the factors associated with the severity of the disease. This will allow the development of risk prevention strategies in Primary Care professionals., Methods: We included all Primary Care professionals of the Territorial Management of Barcelona (GTBCN) notified as suspicion or contact with COVID-19 between March 15 and June 15, 2020. Demographic, clinical and epidemiological variables of the professionals and episodes reported were collected, as well as possible risk factors associated with severity. Descriptive and logistic regression analysis were performed., Results: 1,511 episodes corresponding to 1,427 professionals (31.3% of the GTBCN staff) were reported. 76.4% were women, with a mean age of 45.32 years. Of the professionals reported, 28.5% presented COVID-19 in some episode, and of these 18.2% presented severe symptomatology. Risk factors associated with severity were: respiratory pathology (OR: 2.54, 95%CI: 1.16-5.56) and neoplasia (OR: 4.48, 95%CI: 1.38-14.55)., Conclusions: The proportion of professionals notified due to suspicion or contact with COVID-19 is similar to that observed in other studies, being mostly concentrated in the care categories of primary care teams. The factors associated with symptom severity were previous respiratory disease and neoplasia.

Dietary restriction (DR) decreases body weight, improves health, and extends lifespan. DR can be achieved by controlling how much and/or when food is provided, as well as by adjusting nutritional composition. Because these factors are often combined during DR, it is unclear which are necessary for beneficial effects. Several drugs have been utilized that target nutrient-sensing gene pathways, many of which change expression throughout the day, suggesting that the timing of drug administration is critical. Here, we discuss how dietary and pharmacological interventions promote a healthy lifespan by influencing energy intake and circadian rhythms.

Low birth weight (LBW) is a global problem that annually affects nearly 20 million children, 96% of these in developing countries. According to the WHO, the poorest and the ethnic minorities are the groups most affected by this indicator. A cross-sectional study of the database of all newborns officially registered in Colombia in 2008-2014 was done. While dichotomizing the mestizo population and ethnic minorities (Afro-descendants, indigenous, ROM), normal and low birth weight was used as the dependent variable and ethnicity as the explanatory variable. Other variables of the parents and the newborns were used as covariates. To assess associations, bivariate and multivariate logistic regression analyses were performed. The incidence of LBW among newborns registered in Colombia fluctuated at around 9%. Among the ethnic minorities, the probability of LBW, adjusted for other variables, was significantly higher (OR 1.07, 95% CI 1.05-1.08) than among mestizos. A significantly higher risk of LBW to newborns in the ethnic minorities' group, and those with unfavorable socioeconomic conditions, was found.

Cultivation of the phytopathogenic fungus Botrytis cinerea using sublethal amounts of copper sulfate yielded a cryptic sesquiterpenoids family, which displayed the basic chemical structure of (+)-4-epi-eremophil-9-ene. The biosynthesis pathway was established, and the route involved the likely transformation of the diphosphate of farnesyl (FDP), to give a cis -fused eudesmane cation, through ( S )-hedycaryol, finally yielding the (+)-4-epi-eremophil-9-enol derivatives. An expression study of genes that code for the sesquiterpene cyclases (STC), including the recently reported gene Bcstc7 present in the B. cinerea genome, was performed in order to establish the STC involved in this biosynthesis. The results showed a higher expression level for the Bcstc7 gene with respect to the other stc1-5 genes in both wild-type strains, B05.10 and Botrytis cinerea UCA992. Deletion of the Bcstc7 gene eliminated (+)-4-epi-eremophilenol biosynthesis, which could be re-established by complementing the null mutant with the Bcstc7 gene. Chemical analysis suggested that STC7 is the principal enzyme responsible for the key step of cyclization of FDP to eremophil-9-en-11-ols. Furthermore, a thorough study of the two wild-types and the complemented mutant revealed four new eremophilenol derivatives whose structures are reported here.

Introduction: Leishmaniasis is a zoonotic disease which is caused by protozoan parasites of the genus Leishmania . Canids are the most important reservoir of the parasites; however, limited data are available on the species of Leishmania prevalent in these animals and their impact on human health. The objective of this study was to estimate the seroprevalence of leishmaniasis in dogs from an inter-Andean region of Colombia during July 2016-July 2017, and to describe the clinical and histopathological features of the disease., Material and Methods: A total of 155 dogs were subjected to clinical examination and a serological test for detection of antibodies against Leishmania . Necropsy was carried out on positive animals and tissue samples were processed by routine histopathology., Results: Altogether 19 dogs were positive in the serological test, establishing a 12% seroprevalence of Leishmania . Clinical examination and necropsy revealed exfoliative and ulcerative dermatitis with haemorrhagic borders on the ears, head, nose, and legs. Histopathology revealed severe multifocal dermatitis with abundant Leishmania amastigotes within the cytoplasm of phagocytic cells, depletion of lymphocytes in lymphoid tissues, interstitial pneumonia, and interstitial nephritis. Tissue samples were positive for Leishmania by PCR., Conclusion: The macro- and microscopic changes correlated with the presence of Leishmania as established by serological test and PCR., Competing Interests: Conflict of Interest Conflict of Interests Statement: The authors declare that there is no conflict of interests regarding the publication of this article., (© 2020 Y. Picón et al. published by Sciendo.)

Severe (grades IV and V) vesicoureteral reflux (VUR) is a risk factor for acute pyelonephritis, renal scars, and renal failure. This study evaluates albumin and N-acetylglucosaminidase (NAG) urinary excretion, and renal concentrating ability as screening tools to select patients for voiding cystourethrogram (VCUG). Children (111 M, 52 F) aged 10.97 ± 21.17 months (mean + SD), diagnosed with UTI, and who had undergone renal ultrasound and a VCUG, underwent a desmopressin test and had albumin/creatinine and NAG/creatinine urinary excretion measured. Urine osmolality was significantly lower in 27 children with severe VUR (375.3 ± 171.8 mOsm/kg; mean + SD) compared to 100 patients with normal VCUG (611.5 ± 175.8 mOsm/kg), p < 0.001, and to 36 patients with VUR grades I to III (636.2 ± 180.2 mOsm/kg), p < 0.001. NAG/creatinine ratio was significantly elevated in 20 children with severe VUR (26.4 (28.3) U/g); median and interquartile range compared to 67 children with normal VCUG (10.8 (17.9) U/g), p = 0.003, and to 20 patients with VUR grades I to III (7.6 (21.1) U/g), p = 0.009.Conclusions: Urinary osmolality is significantly decreased and urinary excretion of NAG is significantly increased in patients with severe VUR. These tests could select patients for VCUG to assess for severe VUR. What is Known: • Severe vesicoureteral reflux (SVUR) may contribute to renal damage. Severe vesicoureteral reflux is diagnosed by voiding cystourethrogram and represents about 10% of all patients with VUR. Currently, there are no reliable tests used prior to VCUG to help on the decision of obtaining a VCUG to diagnose SVUR. What is New: • This study shows that renal tubular markers (concentrating ability and N-acetylglucosaminidase (NAG) excretion) are useful tests prior to voiding cystourethrogram to screen for severe vesicoureteral reflux. • This study suggests the use of renal concentrating ability and urinary N-acetylglucosaminidase (NAG) excretion to screen for severe vesicoureteral reflux before requesting a voiding cystourethrogram.

While abscisic acid (ABA) is known as a hormone produced by plants through the carotenoid pathway, a small number of phytopathogenic fungi are also able to produce this sesquiterpene but they use a distinct pathway that starts with the cyclization of farnesyl diphosphate (FPP) into 2Z,4E-α-ionylideneethane which is then subjected to several oxidation steps. To identify the sesquiterpene cyclase (STC) responsible for the biosynthesis of ABA in fungi, we conducted a genomic approach in Botrytis cinerea. The genome of the ABA-overproducing strain ATCC58025 was fully sequenced and five STC-coding genes were identified. Among them, Bcstc5 exhibits an expression profile concomitant with ABA production. Gene inactivation, complementation and chemical analysis demonstrated that BcStc5/BcAba5 is the key enzyme responsible for the key step of ABA biosynthesis in fungi. Unlike what is observed for most of the fungal secondary metabolism genes, the key enzyme-coding gene Bcstc5/Bcaba5 is not clustered with the other biosynthetic genes, i.e., Bcaba1 to Bcaba4 that are responsible for the oxidative transformation of 2Z,4E-α-ionylideneethane. Finally, our study revealed that the presence of the Bcaba genes among Botrytis species is rare and that the majority of them do not possess the ability to produce ABA., (© 2018 Society for Applied Microbiology and John Wiley & Sons Ltd.)

Background: Various genetic and environmental factors are involved in urolithiasis. The 2 most common metabolic abnormalities are the increase in urinary calcium and low urinary citrate excretion. The ratio calculated between the concentrations of both substances is a good risk marker for the formation of calcium stones., Objectives: To determine whether the risk of urinary calcium stone formation changes throughout the day in the same patient., Methods: We studied 56 children (23V, 33M) to check if they had prelithiasis. Calcium, citrate, and creatinine concentrations were determined in two urine samples collected one before dinner and the other in the morning. It was collected if they had ultrasound stones and if there was a history of urolithiasis in first and/or second degree relatives., Results: In 25 patients (44.6%), renal ultrasound was positive for lithiasis (stones [n=9] and microlithiasis [n=16]). Forty of the 56 families (71.4%) had a history of urolithiasis. The percentage of abnormal urinary calcium (28.6%) concentrations and an abnormal calcium/citrate ratio (69.6%) was higher in the first urine of the day. The calcium/citrate ratio was the only studied parameter that was related to a family history of urolithiasis. There were no differences in urinary parameters between patients with and without ultrasound-confirmed kidney stones., Conclusions: Urinary concentrations of calcium and the calcium/citrate ratio vary throughout the day. Urine produced at night has a higher risk of urinary calcium stone formation., (Copyright © 2017 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.)

Filamentous (F-) actin is an integral part of the cytoskeleton allowing for cell growth, intracellular motility, and cytokinesis of eukaryotic cells. Its assembly from G-actin monomers and its disassembly are tightly regulated processes involving a number of actin-binding proteins (ABPs) such as F-actin nucleators and cross-linking proteins. F-actin capping protein (CP) is an alpha/beta heterodimer known from yeast and higher eukaryotes to bind to the fast growing ends of the actin filaments stabilizing them. In this study, we identified the orthologs of the two CP subunits, named BcCPA1 and BcCPB1, in the plant pathogenic fungus Botrytis cinerea and showed that the two proteins physically interact in a yeast two-hybrid approach. GFP-BcCPA1 fusion proteins were functional and localized to the assumed sites of F-actin accumulation, i.e. to the hyphal tips and the sites of actin ring formation. Deletion of bccpa1 had a profound effect on hyphal growth, morphogenesis, and virulence indicating the importance of F-actin capping for an intact actin cytoskeleton. As polarized growth - unlike septum formation - is impaired in the mutants, it can be concluded that the organization and/or localization of actin patches and cables are disturbed rather than the functionality of the actin rings., (Copyright © 2016 British Mycological Society. Published by Elsevier Ltd. All rights reserved.)

The sequencing of the genomes of the B05.10 and T4 strains of the fungus Botrytis cinerea revealed an abundance of novel biosynthetic gene clusters, the majority of which were unexpected on the basis of the previous analyses of the fermentation of these and closely related species. By systematic alteration of easy accessible cultivation parameters, using chemical induction with copper sulfate, we have found a cryptic sesquiterpenoid family with new structures related to eremophil-9-ene, which had the basic structure of the sesquiterpene (+)-5-epiaristolochene ((+)-4-epieremophil-9-ene). An expression study of the sesquiterpene cyclase genes present in the Botrytis cinerea genome, under culture conditions, is reported. In general, a 3 day delay and a higher BcSTC genes expression were observed when copper (5 ppm) was fed to the fermentation broth. In addition, to the observed effect on the BcBOT2 (BcSTC1) gene, involved in the biosynthesis of the botrydial toxin, a higher expression level for BcSTC3 and BcSTC4 was observed with respect to the control in the strain B05.10. Interestingly, under copper conditions, the BcSTC4 gene was the most expressed gene in the Botrytis cinerea UCA992 strain. In vitro evaluation of the biological role of these metabolites indicates that they contributed to the conidial development in B. cinerea and appear to be involved in self-regulation of the production of asexual spores. Furthermore, they promoted the formation of complex appressoria or infection cushions.

Unlabelled: Peptides containing the Arg-Gly-Asp (RGD) sequence have high affinity for αvβ3 integrin receptors overexpressed in tumor cells. The objective of this research was to determine the biodistribution and estimate the radiation dose from (68)Ga-DOTA-E-[c(RGDfK)]2 using whole-body PET scans in humans., Methods: Five healthy volunteers (2 women, 3 men; mean age ± SD, 37.2 ± 15.6 y; range, 28-65 y; mean weight, 79.2 ± 21.0 kg; range, 64-115 kg) were included. After intravenous injection of the tracer (198.3 ± 3.3 MBq), 3 successive whole-body (vertex to mid thigh) PET/CT scans at 3 time points (30, 60, and 120 min) were obtained on a 16-slice PET/CT scanner. The subjects did not void the bladder until the entire series of images was completed. Low-dose CT without contrast agent was used for anatomic localization and attenuation correction. OLINDA/EXM software was applied to calculate human radiation doses using the reference adult model., Results: The highest uptake was in the urinary bladder, followed by the liver, kidneys, and spleen, in descending order. The critical organ was the urinary bladder wall. The mean effective doses (all subjects, men and women) were 34.1 ± 4.9, 31.0 ± 2.4, and 20.9 ± 5.2 μSv/MBq for the no-voiding, 2.5-h-voiding, and 1-h-voiding models, respectively., Conclusion: Of particular interest in this research was the visualization of the choroid plexus and ventricular system, which seems to be a characteristic of RGD-dimeric peptides. Measured absorbed doses and effective doses are comparable to other previously reported RGD-based radiopharmaceuticals labeled with (68)Ga and (18)F. Therefore, (68)Ga-DOTA-E-[c(RGDfK)]2 can safely be used for imaging integrin αVβ3 expression., (© 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)

Wines can be modified by microorganisms during the ageing process, by producing off-flavours like volatile phenols (VP), leading to their deterioration, with great economic losses. The development of methods to recover wines affected by unwanted VP became an important target. Molecular imprinted polymers (MIPs) are synthetic materials with artificially-generated recognition sites for selective extraction of organic compounds from different matrices. In this work, two MIPs to remove unwanted VP from wines were developed and their effects were evaluated. Volatile compounds were determined by GC-FID and GC-IT/MS and phenolic compounds (non-coloured and anthocyanins) by HPLC-DAD. The treatment with MIP-4EG and MIP-4EP significantly reduced the content of 4-ethylguaiacol and 4-ethylphenol, respectively. Nevertheless, the changes observed in wine non-coloured and coloured phenolics and sensorial analysis indicate that their specificity and selectivity regarding off-flavours still needs to be improved.

Introduction: Eight Giardia duodenalis genotypes (A-H) have been described to date. Genotypes A and B have been isolated from humans and a wide range of mammals; however, genotypes C-H have shown greater host specificity., Objective: Identifying G. duodenalis genotypes from cysts in faeces obtained from children attending the Instituto Colombiano de Bienestar Familiar (ICBF) day care centres and from dogs in Ibagué by PCR-RFLP targeting both the b -giardin and glutamate dehydrogenase genes., Materials and Methods: Cysts from G. duodenalis positive samples were concentrated, DNA was extracted and the b -giardin and glutamate dehydrogenase genes were analysed by PCR-RFLP. The MHOM/CO/04/G40 strain was used as positive control (this was obtained from the Grupo de Parasitología at the Instituto Nacional de Salud )., Results: Of the total human samples, 11/23 (48%) were genotyped as A and 12/23 (52%) as B; PCR-RFLP revealed that four canine samples were genotypes C and D, these being host-specific., Conclusions: Only genotypes associated with human infection (AII, BIII and BIV) were found in the children and host-specific genotypes were observed in canines (C and D). No interaction could be established between animal and human transmission cycles due to the small canine sample size and as the former did not come into contact with children attending ICBF day-care centres.

Introduction: We analysed a large sample of children diagnosed with urinary tract malformations and/or infections and calculated diagnostic efficiency and quality indexes for five different functional markers, with the goal of testing which is the most sensitive for detecting a loss of renal parenchyma., Patients and Method: Ours was a cross-sectional retrospective study in which the clinical histories of 179 paediatric patients (91 male and 88 female) were evaluated. In 102 of these patients (57%), a scintigraphy revealed loss of parenchyma. The most commonly observed morphological type of damage was renal scarring. All patients had undergone at least one desmopressin urine concentration test. We also analysed albumin/creatinine and N-acetyl-glucosaminidase (NAG)/creatinine ratios, glomerular filtration rate (GFR), and urine volume., Results: By distributing patients according to normal/abnormal scintigraphy, we observed statistically significant differences between the two groups in maximum urine osmolality and GFR. Urine volume was elevated in 31.3% of cases (sensitivity: 37.9%; specificity: 81.8%) and 24% had a defect in renal concentrating ability (sensitivity: 30.4%; specificity: 84.8%). Urinary albumin excretion was high in 12.2% of patients, and 7.2% had a high NAG/creatinine ratio. GFR was low in only 5.7% of patients. These last two markers were the least sensitive but most specific for detecting a loss of renal parenchyma (100%)., Conclusions: In our study, the most sensitive functional tests for detecting the loss of renal parenchyma were the two that take into account the ability of the kidney to manage water, i.e. urine volume and maximum urine osmolality. These two tests had specificity >80%. However, the maximum specificity was obtained by the NAG/creatinine ratio and GFR, which were, conversely, the least sensitive tests. A normal GFR does not necessarily show normal renal function.

Objectives: In this paper we describe the history of lithiasis and the development of its treatment. We discuss the steps that led to the birth of endoscopic surgery and extracorporeal shockwave lithotripsy., Methods: We reviewed books and writings of History of Urology and Endourology., Results/conclusions: To know a little of the history and treatment of lithiasis, the contributions of Spanish urologists, as well as the instruments that made it possible.

Objectives: The objective of this work is to analyze the treatment of staghorn calculi at our Department of Urology. We have to know the recent development of endoscopic surgery (percutaneous renal surgery) and external shock wave lithotripsy., Methods: We reviewed the surgical management of staghorn calculi during the period between 1987 and 2004., Results: Percutaneous renal surgery was performed successfully in 24.1% of the cases. Persisting residual fragments appeared in 75.9% and were treated by ESWL or second endoscopic surgery., Conclusions: Percutaneous renal surgery may be considered the technique of choice to treat staghorn calculi. Endoscopic surgery has good results and little complications with low morbidity. In other cases the treatment is combined therapy, percutaneous renal surgery and ESWL.

Objectives: The goal of this work is to evaluate the usefulness of NMP22 BladderChek in the diagnosis and follow-up of bladder cancer, comparing it with cystoscopy and urine cytology., Methods: Group 1: 109 asymptomatic patients on follow up for bladder cancer underwent cystoscopy, cytology and NMP22 BladderChek. Group 2:15 patients with history of hematuria underwent cystoscopy and NMP22 BladderChek., Results: Group 1: 9 patients had tumor relapse. Sensitivity was 25% for NMP22 test, 50% for citology and 100% for cystoscopy Specificity was 91.1%, 94.1% and 95% respectively. Group 2: 12 patients had bladder cancer. The sensitivity was of 83.3% for NMP22 BladderChek and 100% for cystoscopy. The specificity was of 100% for NMP22 BladderChek and 66.7% for cystoscopy., Conclusions: The low sensitivity of NMP22 Bladder-Chek invalidates it as alternative method to cystoscopy in the follow-up of bladder cancer. But it can be recommended for screening in patients without history of bladder cancer but with an increased risk (smokers, patients with dysuria and hematuria).

Objectives: To show the beginning of spinal and epidural anesthesia in our country and the contributions of Spanish urologists., Methods: We reviewed books and writings of History of Medicine, Urology and Anesthesia and Doctoral thesis about spinal and epidural anesthesia., Results: In the 20th century, surgeons also gave the anesthetic drugs to the patients. Spinal and epidural anesthesia were used for the first time in 1900. A lot of Spanish urologists like F Rusca Doménech, J.M. Batrina, M. Barragán Bonet, R. Lozano Monzón, L. Guedea Calvo, Gil Vernet, Fidel Pagés Miravé, V Sagarra Lascurain, Gómez Ulla, etc, did research, writings in scientific journals and Doctoral thesis about anesthesia.