Biological Rhythms Generated by a Single Activator-Repressor Loop with Inhomogeneity and Diffusion.

Common models of circadian rhythms are typically constructed as compartmental reactions of well-mixed biochemicals, incorporating a negative-feedback loop consisting of several intermediate reaction steps essentially required to produce oscillations. Spatial transport of each reactant is often represented as an extra compartmental reaction step. Contrary to this traditional understanding, in this Letter we demonstrate that a single activation-repression biochemical reaction pair is sufficient to generate sustained oscillations if the sites of both reactions are spatially separated and molecular transport is mediated by diffusion. Our proposed scenario represents the simplest configuration in terms of the participating chemical reactions and offers a conceptual basis for understanding biological oscillations and inspiring in vitro assays aimed at constructing minimal clocks.

Bacillus licheniformis M2-7 Decreases Ochratoxin A Concentrations in Coffee Beans During Storage.

Microbial contamination of coffee beans arises from various factors such as harvesting, handling, and storage practices, during which ochratoxin A (OTA)-producing fungi develop and proliferate. The presence of elevated concentrations of OTA poses a serious health risk to coffee consumers. Therefore, the implementation of a post-harvest treatment involving the use of bacteria known to antagonize OTA-producing fungi constitutes a safe alternative for reducing or eliminating the toxin's concentration in coffee beans. In this study, coffee beans (Coffea arabica L.) were inoculated with Bacillus licheniformis M2-7, after which we monitored fungal growth, in vitro antagonism, and OTA concentration. Our findings demonstrated that coffee beans inoculated with this bacterial strain exhibited a significant decrease in fungal populations belonging to the genera Aspergillus and Penicillium, which are known to produce OTA. Moreover, strain M2-7 decreased the growth rates of these fungi from 67.8% to 95.5% (P < 0.05). Similarly, inoculation with B. licheniformis strain M2-7 effectively reduced the OTA concentration from 24.35 ± 1.61 to 5.52 ± 1.69 µg/kg (P < 0.05) in stored coffee beans. These findings suggest that B. licheniformis M2-7 holds promise as a potential post-harvest treatment for coffee beans in storage, as it effectively inhibits the proliferation of OTA-producing fungi and lowers the toxin's concentration.

Can We Predict Prostate Cancer Metastasis Based on Biomarkers? Where Are We Now?

The incidence of prostate cancer (PC) has risen annually. PC mortality is explained by the metastatic disease (mPC). There is an intermediate scenario in which patients have non-mPC but have initiated a metastatic cascade through epithelial-mesenchymal transition. There is indeed a need for more and better tools to predict which patients will progress in the future to non-localized clinical disease or already have micrometastatic disease and, therefore, will clinically progress after primary treatment. Biomarkers for the prediction of mPC are still under development; there are few studies and not much evidence of their usefulness. This review is focused on tissue-based genomic biomarkers (TBGB) for the prediction of metastatic disease. We develop four main research questions that we attempt to answer according to the current evidence. Why is it important to predict metastatic disease? Which tests are available to predict metastatic disease? What impact should there be on clinical guidelines and clinical practice in predicting metastatic disease? What are the current prostate cancer treatments? The importance of predicting metastasis is fundamental given that, once metastasis is diagnosed, quality of life (QoL) and survival drop dramatically. There is still a need and space for more cost-effective TBGB tests that predict mPC disease.

[Prognostic factors in patients with upper urinary tract urothelial carcinoma undergoing nephro-ureterectomy]. / Tabaquismo y tumores mayores de 2 centímetros son predictores de mortalidad en pacientes sometidos a nefro-ureterectomías por carcinoma de urotelio alto.

BACKGROUND: Upper urinary tract urothelial carcinoma (UTUC) represents 5-10% of urothelial carcinomas. It is managed with nephroureterectomy (NUR); however, kidney-sparing techniques are growingly used. AIM: To report the results of a 20-year series of NUR conducted in an academic center. PATIENTS AND METHODS: Review of clinical and pathological characteristics of patients undergoing NUR between 1999 and 2020. Patients were followed for 63 months. Global survival curves (OS) and mortality predictors were established through Cox regression. RESULTS: We included 90 patients with a median age of 68 years undergoing NUR, of whom 68 (75%) had a pelvic tumor and 22 (25%) had a proximal ureteral tumor. A laparoscopic NUR was performed in 60 patients (66%). Thirty-three patients (37%) had tumors confined to the urothelium (pTa), penetrating the lamina propria (pT1) or carcinoma in situ (CIS), 10 patients (11%) had a tumor spreading to the muscle layer (pT2) and 47 (52%) had a tumor spreading to nearby organs (pT3 / T4). Average tumor size was 3.69 cm, nodal disease (pN) was present 12 patients (13%). Twelve patients (13%) received adjuvant chemotherapy. A higher mortality was observed among smokers (Hazard ratio (HR) 8.79, 95% confidence intervals (CI) 1.5-49.0, p = 0.01), patients with tumors classfied as pT≥ 2 (HR 1.09, 95% CI 0.01-1.0, p = 0.04) and those with tumors larger than 2 cm (HR 14.79, CI 95% 1.5-272, p = 0.01). CONCLUSIONS: Smoking patients, those with invasive tumors (T2-T4) and greater than 2 cm have higher mortality. Therefore, they should not be candidates for conservative management.

[Vena cava thrombectomy in kidney cancer. Report of 32 nephrectomies]. / Nefrectomía radical con trombectomía de vena cava: 20 años de cirugías por tumor renal.

BACKGROUND: Vena cava (VC) involvement in kidney tumors occurs in 4 to 10% of cases, and is associated with a higher mortality. Nephrectomy with thrombectomy of the VC, performed by a multidisciplinary team, improves survival. AIM: To report a series of consecutive nephrectomies with caval thrombectomy performed in an academic center. PATIENTS AND METHODS: We report 32 patients with cT3b and 3c renal tumors, who underwent radical nephrectomy with VC thrombectomy between 2001 and 2021. A descriptive analysis of clinical, surgical and pathological variables was performed. Overall survival (OS) and cancer-specific survival (CSS) was calculated using Kaplan-Meier curves. RESULTS: The mean tumor size was 9.7 cm. According to Mayo classification 3/32 (9%) patients had a type I thrombus, 10/32 (31%) had a type II thrombus, 8/32 (25%) had a type III thrombus, and 5/32 (16%) had a type IV thrombus. The mean bleeding was 2000 cc. There was one intraoperative death. Nineteen percent of patients had complications >= 3 according to Clavien-Dindo classification. Reoperations occurred in 9%. Pre and postoperative creatinine levels were 1.17 and 1.91 mg/dl respectively (p < 0.01). Pre and postoperative Hematocrit levels were 47.9 and 31% respectively (p = 0.02). Sixty six percent of tumors were clear cell renal cancer, 9% were papillary and 3% were chromophobic. Mean OS was 10 months. Two-year SCE was 40%. CONCLUSIONS: Our results are similar to those reported elsewhere. Despite being an unusual pathology, the surgical technique has been improving, thanks to the multidisciplinary work of urologists and surgeons.

Protective role of intravesical BCG in COVID-19 severity.

OBJECTIVES: To establish the role of BCG instillations in the incidence and mortality of COVID-19. PATIENTS AND METHODS: NMIBC patients in instillations with BCG (induction or maintenance) during 2019/2020 were included, establishing a COVID-19 group (with a diagnosis according to the national registry) and a control group (NO-COVID). The cumulative incidence (cases/total patients) and the case fatality rate (deaths/cases) were established, and compared with the national statistics for the same age group. T-test was used for continuous variables and Fisher's exact test for categorical variables. RESULTS: 175 patients were included. Eleven patients presented CIS (11/175, 6.3%), 84/175 (48.0%) Ta and 68/175 (38.9%) T1. Average number of instillations = 13.25 ± 7.4. One hundred sixty-seven patients (95.4%) had complete induction. Forty-three patients (cumulative incidence 24.6%) were diagnosed with COVID-19. There is no difference between COVID-19 and NO-COVID group in age, gender or proportion of maintenance completed. COVID-19 group fatality rate = 1/43 (2.3%). Accumulated Chilean incidence 70-79 years = 6.3%. Chilean fatality rate 70-79 years = 14%. CONCLUSIONS: According to our results, patients with NMIBC submitted to instillations with BCG have a lower case-fatality rate than the national registry of patients between 70 and 79 years (2.3% vs. 14%, respectively). Intravesical BCG could decrease the mortality due to COVID-19, so instillation schemes should not be suspended in a pandemic.

Bladder squamous cell carcinoma in a pregnant woman: case report and review of the literature.

BACKGROUND: Bladder tumors in pregnancy are extremely rare. No more than 50 cases have been published to date, including all histologic variants, and only three cases of bladder squamous cell carcinoma have been described. CASE PRESENTATION: We present a clinical case of a 31-year-old woman with bladder squamous cell carcinoma in the second trimester of pregnancy. After a C-section at 30 weeks, we performed radical cystectomy with extended bilateral lymphadenectomy, hysterectomy and right oophorectomy. The Studer neobladder technique was performed for urinary tract reconstruction. Definitive pathology showed invasive bladder squamous cell carcinoma, Grade 2, with microscopic infiltration of the perivesical fat, negative margins, and 3/28 lymph nodes with carcinoma (pT3aN2M0). The patient underwent 18 months of surveillance after radical cystectomy, without recurrence by PET-CT. CONCLUSIONS: Bladder cancer in pregnant women is extremely rare but must be considered in those with recurrent gross hematuria and/or recurrent urinary tract infection. To our knowledge, this case involves the longest recurrence-free survival of a pregnant woman with squamous cell bladder cancer published thus far.

Interdisciplinary Online Hackathons as an Approach to Combat the COVID-19 Pandemic: Case Study.

BACKGROUND: The COVID-19 outbreak has affected the lives of millions of people by causing a dramatic impact on many health care systems and the global economy. This devastating pandemic has brought together communities across the globe to work on this issue in an unprecedented manner. OBJECTIVE: This case study describes the steps and methods employed in the conduction of a remote online health hackathon centered on challenges posed by the COVID-19 pandemic. It aims to deliver a clear implementation road map for other organizations to follow. METHODS: This 4-day hackathon was conducted in April 2020, based on six COVID-19-related challenges defined by frontline clinicians and researchers from various disciplines. An online survey was structured to assess: (1) individual experience satisfaction, (2) level of interprofessional skills exchange, (3) maturity of the projects realized, and (4) overall quality of the event. At the end of the event, participants were invited to take part in an online survey with 17 (+5 optional) items, including multiple-choice and open-ended questions that assessed their experience regarding the remote nature of the event and their individual project, interprofessional skills exchange, and their confidence in working on a digital health project before and after the hackathon. Mentors, who guided the participants through the event, also provided feedback to the organizers through an online survey. RESULTS: A total of 48 participants and 52 mentors based in 8 different countries participated and developed 14 projects. A total of 75 mentorship video sessions were held. Participants reported increased confidence in starting a digital health venture or a research project after successfully participating in the hackathon, and stated that they were likely to continue working on their projects. Of the participants who provided feedback, 60% (n=18) would not have started their project without this particular hackathon and indicated that the hackathon encouraged and enabled them to progress faster, for example, by building interdisciplinary teams, gaining new insights and feedback provided by their mentors, and creating a functional prototype. CONCLUSIONS: This study provides insights into how online hackathons can contribute to solving the challenges and effects of a pandemic in several regions of the world. The online format fosters team diversity, increases cross-regional collaboration, and can be executed much faster and at lower costs compared to in-person events. Results on preparation, organization, and evaluation of this online hackathon are useful for other institutions and initiatives that are willing to introduce similar event formats in the fight against COVID-19.

Catalyzing sustainable fisheries management through behavior change interventions.

Small-scale fisheries are an important livelihood and primary protein source for coastal communities in many of the poorest regions in the world, yet many are overfished and thus require effective and scalable management solutions. Positive ecological and socioeconomic responses to management typically lag behind immediate costs borne by fishers from fishing pressure reductions necessary for fisheries recovery. These short-term costs challenge the long-term success of these interventions. However, social marketing may increase perceptions of management benefits before ecological and socioeconomic benefits are fully realized, driving new social norms and ultimately long-term sustainable behavior change. By conducting underwater visual surveys to quantify ecological conditions and by conducting household surveys with community members to quantify their perceptions of management support and socioeconomic conditions, we assessed the impact of a standardized small-scale fisheries management intervention that was implemented across 41 sites in Brazil, Indonesia, and the Philippines. The intervention combines TURF reserves (community-based territorial use rights for fishing coupled with no-take marine reserves) with locally tailored social-marketing behavior change campaigns. Leveraging data across 22 indicators and 4 survey types, along with data from 3 control sites, we found that ecological and socioeconomic impacts varied and that communities supported the intervention and were already changing their fishing practices. These results suggest that communities were developing new social norms and fishing more sustainably before long-term ecological and socioeconomic benefits of fisheries management materialized.

Catalización del Manejo de Pesquerías Sustentables por medio de Intervenciones de Cambio de Comportamiento Resumen Las pesquerías a pequeña escala son un sustento importante y la principal fuente de proteína para las comunidades costeras en muchas de las regiones más pobres del mundo, sin embargo, muchas sufren de sobrepesca y por lo tanto requieren soluciones de manejo efectivas y escalables. Las respuestas ecológicas y socioeconómicas positivas al manejo generalmente se retrasan con respecto a los costos inmediatos asumidos por los pescadores a partir de las reducciones de la presión ocasionada por la pesca necesarias para la recuperación de la pesquería. Estos costos a corto plazo son un reto para el éxito a largo plazo de las intervenciones. Sin embargo, la mercadotecnia social puede incrementar las percepciones de los beneficios del manejo antes de que se conozcan por completo los beneficios ecológicos y socioeconómicos, lo que genera nuevas normas sociales y finalmente un cambio en el comportamiento a largo plazo. Realizamos censos submarinos visuales para cuantificar las condiciones ecológicas y censos domésticos a los miembros de la comunidad para cuantificar sus percepciones del apoyo al manejo y de las condiciones socioeconómicas. Con esto, evaluamos el impacto de la intervención de manejo para pesquerías estandarizadas a pequeña escala que fue implementada en 41 sitios de Brasil, Indonesia y las Filipinas. La intervención combina las reservas TURF (derechos de uso de pesca territorial basados en la comunidad acoplados con reservas marinas con restricción de pesca) con campañas de mercadotecnia social para el cambio de comportamiento ajustadas al contexto local. Con la movilización de datos a lo largo de 22 indicadores y cuatro tipos de censos, junto con los datos de tres sitios de control, encontramos que los impactos ecológicos y socioeconómicos variaron y que las comunidades apoyaban la intervención y ya se encontraban cambiando sus prácticas de pesca. Estos resultados sugieren que las comunidades ya estaban desarrollando nuevas normas sociales y pescando de manera más sustentable antes de que los beneficios ecológicos y socioeconómicos a largo plazo del manejo de las pesquerías se materializaran.

Hackathons as Stepping Stones in Health Care Innovation: Case Study With Systematic Recommendations.

BACKGROUND: Until recently, developing health technologies was time-consuming and expensive, and often involved patients, doctors, and other health care professionals only as passive recipients of the end product. So far, users have been minimally involved in the ideation and creation stages of digital health technologies. In order to best address users' unmet needs, a transdisciplinary and user-led approach, involving cocreation and direct user feedback, is required. In this context, hackathon events have become increasingly popular in generating enthusiasm for user-centered innovation. OBJECTIVE: This case study describes preparatory steps and the performance of a health hackathon directly involving patients and health care professionals at all stages. Feasibility and outcomes were assessed, leading to the development of systematic recommendations for future hackathons as a vehicle for bottom-up innovation in health care. METHODS: A 2-day hackathon was conducted in February 2017 in Berlin, Germany. Data were collected through a field study. Collected field notes were subsequently discussed in 15 informal meetings among the research team. Experiences of conducting two further hackathons in December 2017 and November 2018 were included. RESULTS: In total, 30 participants took part, with 63% (19/30) of participants between 25 and 34 years of age, 30% (9/30) between 35 and 44 years of age, and 7% (2/30) younger than 25 years of age. A total of 43% (13/30) of the participants were female. The participation rate of medical experts, including patients and health care professionals, was 30% (9/30). Five multidisciplinary teams were formed and each tackled a specific health care problem. All presented projects were apps: a chatbot for skin cancer recognition, an augmented reality exposure-based therapy (eg, for arachnophobia), an app for medical neighborhood connectivity, a doctor appointment platform, and a self-care app for people suffering from depression. Patients and health care professionals initiated all of the projects. Conducting the hackathon resulted in significant growth of the digital health community of Berlin and was followed up by larger hackathons. Systematic recommendations for conducting cost-efficient hackathons (n≤30) were developed, including aspects of community building, stakeholder engagement, mentoring, themes, announcements, follow-up, and timing for each step. CONCLUSIONS: This study shows that hackathons are effective in bringing innovation to health care and are more cost- and time-efficient and potentially more sustainable than traditional medical device and digital product development. Our systematic recommendations can be useful to other individuals and organizations that want to establish user-led innovation in academic hospitals by conducting transdisciplinary hackathons.

[Small renal masses. Analysis of 152 cases]. / Masas renales pequeñas: predictores de malignidad en una serie de 10 años.

BACKGROUND: Small renal masses (SRM) are defined as complex organ-confined solid or cystic lesions < 4 cm. Up to 20% of these can be benign. A conservative management with active surveillance can be done in some patients. However, it is difficult to identify patients with a higher risk of malignancy. AIM: To characterize the clinical, radiological and histopathological aspects of patients with SRM, analyzing predictive factors for tumor aggressiveness. MATERIAL AND METHODS: Retrospective analysis of a cohort of patients undergoing partial or total nephrectomy for renal tumors between 2006 and 2016. All tumors of 4 cm or less were included. Four histological groups were defined: benign, favorable, intermediate and unfavorable. Two categories of risk were also defined: low and high. Preoperative clinical and radiological variables of these patients were analyzed. RESULTS: Data of 152 patients were analyzed. Six percent had a benign histology, and the majority was of intermediate risk (74%). According to histological type, clear cell carcinoma was the most common type (74%). Three percent were benign angiomyolipomas. No malignancy predictive variable was identified. CONCLUSIONS: In these patients, the percentage of benign SRM was low. No variable that could predict the presence of a benign or malignant lesion in the definitive biopsy was identified.

Sample size estimation for heterogeneous growth curve models with attrition.

In this study, two approaches were employed to calculate how large the sample size needs to be in order to achieve a desired statistical power to detect a significant group-by-time interaction in longitudinal intervention studies-a power analysis method, based on derived formulas using ordinary least squares estimates, and an empirical method, based on restricted maximum likelihood estimates. The performance of both procedures was examined under four different scenarios: (a) complete data with homogeneous variances, (b) incomplete data with homogeneous variances, (c) complete data with heterogeneous variances, and (d) incomplete data with heterogeneous variances. Several interesting findings emerged from this research. First, in the presence of heterogeneity, larger sample sizes are required in order to attain a desired nominal power. The second interesting finding is that, when there is attrition, the sample size requirements can be quite large. However, when attrition is anticipated, derived formulas enable the power to be calculated on the basis of the final number of subjects that are expected to complete the study. The third major finding is that the direct mathematical formulas allow the user to rigorously determine the sample size required to achieve a specified power level. Therefore, when data can be assumed to be missing at random, the solution presented can be adopted, given that Monte Carlo studies have indicated that it is very satisfactory. We illustrate the proposed method using real data from two previously published datasets.

Distribution and phylogeny of Brachyspira spp. in human intestinal spirochetosis revealed by FISH and 16S rRNA-gene analysis.

During six years as German National Consultant Laboratory for Spirochetes we investigated 149 intestinal biopsies from 91 patients, which were histopathologically diagnosed with human intestinal spirochetosis (HIS), using fluorescence in situ hybridization (FISH) combined with 16S rRNA gene PCR and sequencing. Aim of this study was to complement histopathological findings with FISH and PCR for definite diagnosis and species identification of the causative pathogens. HIS is characterized by colonization of the colonic mucosa of the human distal intestinal tract by Brachyspira spp. Microbiological diagnosis of HIS is not performed, because of the fastidious nature and slow growth of Brachyspira spp. in culture. In clinical practice, diagnosis of HIS relies solely on histopathology without differentiation of the spirochetes. We used a previously described FISH probe to detect and identify Brachyspira spp. in histological gut biopsies. FISH allowed rapid visualization and identification of Brachyspira spp. in 77 patients. In most cases, the bright FISH signal already allowed rapid localization of Brachyspira spp. at 400× magnification. By sequencing, 53 cases could be assigned to the B. aalborgi lineage including "B. ibaraki" and "B. hominis", and 23 cases to B. pilosicoli. One case showed mixed colonization. The cases reported here reaffirm all major HIS Brachyspira spp. clusters already described. However, the phylogenetic diversity seems to be even greater than previously reported. In 14 cases, we could not confirm HIS by either FISH or PCR, but found colonization of the epithelium by rods and cocci, indicating misdiagnosis by histopathology. FISH in combination with molecular identification by 16S rRNA gene sequencing has proved to be a valuable addition to histopathology. It provides definite diagnosis of HIS and allows insights into phylogeny and distribution of Brachyspira spp. HIS should be considered as a differential diagnosis in diarrhea of unknown origin, particularly in patients from risk groups (e.g. patients with colonic adenomas, inflammatory polyps, inflammatory bowel disease or HIV infection and in men who have sex with men).

Fluorescence in situ hybridization for the identification of Treponema pallidum in tissue sections.

Syphilis is often called the great imitator because of its frequent atypical clinical manifestations that make the disease difficult to recognize. Because Treponema pallidum subsp. pallidum, the infectious agent of syphilis, is yet uncultivated in vitro, diagnosis is usually made using serology; however, in cases where serology is inconclusive or in patients with immunosuppression where these tests may be difficult to interpret, the availability of a molecular tool for direct diagnosis may be of pivotal importance. Here we present a fluorescence in situ hybridization (FISH) assay that simultaneously identifies and analyzes spatial distribution of T. pallidum in histological tissue sections. For this assay the species-specific FISH probe TPALL targeting the 16S rRNA of T. pallidum was designed in silico and evaluated using T. pallidum infected rabbit testicular tissue and a panel of non-syphilis spirochetes as positive and negative controls, respectively, before application to samples from four syphilis-patients. In a HIV positive patient, FISH showed the presence of T. pallidum in inguinal lymph node tissue. In a patient not suspected to suffer from syphilis but underwent surgery for phimosis, numerous T. pallidum cells were found in preputial tissue. In two cases with oral involvement, FISH was able to differentiate T. pallidum from oral treponemes and showed infection of the oral mucosa and tonsils, respectively. The TPALL FISH probe is now readily available for in situ identification of T. pallidum in selected clinical samples as well as T. pallidum research applications and animal models.

Effects of Modeling the Heterogeneity on Inferences Drawn from Multilevel Designs.

This article uses Monte Carlo techniques to examine the effect of heterogeneity of variance in multilevel analyses in terms of relative bias, coverage probability, and root mean square error (RMSE). For all simulated data sets, the parameters were estimated using the restricted maximum-likelihood (REML) method both assuming homogeneity and incorporating heterogeneity into multilevel models. We find that (a) the estimates for the fixed parameters are unbiased, but the associated standard errors are frequently biased when heterogeneity is ignored; by contrast, the standard errors of the fixed effects are almost always accurate when heterogeneity is considered; (b) the estimates for the random parameters are slightly overestimated; (c) both the homogeneous and heterogeneous models produce standard errors of the variance component estimates that are underestimated; however, taking heterogeneity into account, the REML-estimations give correct estimates of the standard errors at the lowest level and lead to less underestimated standard errors at the highest level; and (d) from the RMSE point of view, REML accounting for heterogeneity outperforms REML assuming homogeneity; a considerable improvement has been particularly detected for the fixed parameters. Based on this, we conclude that the solution presented can be uniformly adopted. We illustrate the process using a real dataset.

Association of RNASEL and 8q24 variants with the presence and aggressiveness of hereditary and sporadic prostate cancer in a Hispanic population.

To study the association between the polymorphisms Arg462Gln and Asp541Glu from the RNASEL gene (1q25), and the polymorphisms rs620861, rs1447295, rs6983267, rs7837328 from the chromosome 8q24 with the risk of presenting prostate cancer (PCa) and its clinical characteristics in a Hispanic (Chilean) population. The study was performed on 21 control patients and 83 patients diagnosed with PCa. Polymorphisms were analysed from blood samples through real-time PCR by using TaqMan probes, and the genetic analysis was performed with the SNPStats program. Also, a comparison was performed between clinical characteristics of PCa and the presence of the different polymorphism genotypes by using the Minitab software. There was a significant association between the genotype G/G from the polymorphism rs6983267 with an overall increased risk of PCa, in patients both with or without family history of PCa (OR = 4.47, 95% CI = 1.05-18.94, P = 0.034 and OR = 3.57, 95% CI = 0.96-13.35, P = 0.037, respectively). Regarding clinical parameters, patients carrying the genotype C/C from the polymorphism Asp541Glu had significantly higher prostate-specific antigen (PSA) levels than patients carrying the other genotypes (P = 0.034). Moreover, patients with the genotype G/G of rs6983267 had higher PSA levels (P = 0.024). The polymorphism rs6983267 from region 3 of the chromosome 8q24 appears to be a prominent risk factor for PCa and a biomarker for cancer aggressiveness in the group of patients who presented higher levels of PSA at the time of diagnosis.

Low free testosterone levels predict disease reclassification in men with prostate cancer undergoing active surveillance.

OBJECTIVE: To determine whether total testosterone and free testosterone levels predict disease reclassification in a cohort of men with prostate cancer (PCa) on active surveillance (AS). PATIENTS AND METHODS: Total testosterone and free testosterone concentrations were determined at the time the men began the AS protocol. Statistical analysis was performed using Student's t-test and a chi-squared test to compare groups. Odds ratios (ORs) with 95% confidence intervals (CIs) were obtained using univariate logistic regression. Receiver-operator characteristic curves were generated to determine the investigated testosterone thresholds. Kaplan-Meier curves were used to estimate time to disease reclassification. A Cox proportional hazard regression model was used for multivariate analysis. RESULTS: A total of 154 men were included in the AS cohort, of whom 54 (35%) progressed to active treatment. Men who had disease reclassification had significantly lower free testosterone levels than those who were not reclassified (0.75 vs 1.02 ng/dL, P = 0.03). Men with free testosterone levels <0.45 ng/dL had a higher rate of disease reclassification than patients with free testosterone levels ≥0.45 (P = 0.032). Free testosterone levels <0.45 ng/dL were associated with a several-fold increase in the risk of disease reclassification (OR 4.3, 95% CI 1.25-14.73). Multivariate analysis showed that free testosterone and family history of PCa were independent predictors of disease reclassification. CONCLUSIONS: Free testosterone levels were lower in men with PCa who had reclassification during AS. Men with moderately severe reductions in free testosterone level are at increased risk of disease reclassification.

Usefulness of Tissue Biomarkers versus Prostate-Specific Membrane Antigen-Positron Emission Tomography for Prostate Cancer Biochemical Recurrence after Radical Prostatectomy.

Despite curative-intent local therapy, approximately 27% to 53% of prostate cancer (PCa) patients experience prostate-specific antigen (PSA) recurrence, known as biochemical recurrence (BCR). BCR significantly raises the risk of PCa-related morbidity and mortality, yet there is no consensus on optimal management. Prostate-specific membrane antigen-positron emission tomography (PSMA PET) has emerged as highly sensitive imaging, distinguishing local recurrences from distant metastases, crucially influencing treatment decisions. Genomic biomarkers such as Decipher, Prolaris, and Oncotype DX contribute to refining recurrence risk profiles, guiding decisions on intensifying adjuvant therapies, like radiotherapy and androgen deprivation therapy (ADT). This review assesses PSMA PET and biomarker utility in post-radical prostatectomy BCR scenarios, highlighting their impact on clinical decision-making. Despite their promising roles, the routine integration of biomarkers is limited by availability and cost, requiring further evidence. PSMA PET remains indispensable for restaging and treatment evaluation in these patients. Integrating biomarkers and PSMA PET promises to optimize personalized management strategies for BCR, though more comprehensive consensus-building studies are needed to define their standardized utility in clinical practice.

Validation and analysis of the metric properties of the Leadership Virtues Questionnaire in work and organizational psychologists and individuals who perform leadership functions in Chile.

The literature on leadership and personal competencies exhibits limitations in terms of construct definition, behavior specifications and valid theory-based measuring strategies. An explanatory design with latent variables and the statistical software SAS 9.4 were used for the validation and adaptation to Spanish of the Leadership Virtues Questionnaire applied to work and organizational psychologists and people who exercise leadership functions in Chile. The levels of agreement between judges for the adaptation to the Spanish language and the confirmatory factor analysis of first order with four dimensions shows insufficient statistical indices for the absolute, comparative and parsimonious adjustments. However, a second-order confirmatory factor analysis with two dimensions presents a satisfactory fit for the item, model, and parameter matrices. The measurement of Virtuous Leadership would provide relevant inputs for further evaluation and training based on ethical competencies aimed at improving management, which would, in turn, allow for its treatment as an independent variable to generate an ethical organizational culture.

Intensity-modulated radiotherapy versus radical prostatectomy in patients with localized prostate cancer: long-term follow-up.

BACKGROUND: The objective of this work was to assess the overall survival, cause-specific survival and biochemical failure-free survival of a contemporary cohort of patients with localized prostate cancer (PCa) treated with intensity-modulated radiation therapy (IMRT) or radical prostatectomy (RP). METHODS: We did a retrospective cohort study of our institution's registry of patients undergoing either IMRT or RP between January 1999 and March 2010, and assessed Prostate Specific Antigen (PSA), age at diagnosis, Gleason score, and digital rectal examination. Two groups were separated according to RP or IMRT treatment and these groups were in turn divided into risk groups according to the D'Amico classification. Overall survival (OS), cause-specific survival (CSS), mortality from other causes (MOC), and biochemical disease-free survival (BDFS) were assessed. RESULTS: Twelve-hundred patients were included: 993 in the RP group and 207 in the IMRT group.The IMRT group had older age, PSA at diagnosis and a significantly higher percentage of cancer on the needle biopsy (p <0.001). Of the 207 patients who underwent IMRT, 54% presented comorbidities. Median follow-up was 91.7 months for the RP group and 76 months for the IMRT group. The OS at 5 and 7 was 96.2, and 93.7 for the RP group respectively and 88.4, and 83.1 for the IMRT group respectively (p <0.001). There were no significant differences in the CSS in relation to treatment received among the low- and high-risk groups, while in the intermediate-risk group, patients who underwent to RP had a higher CSS than patients who underwent IMRT (99.6% vs 94.1%, p=0.003). The IMRT group had a significantly better BDFS than the RP group (86.4% vs. 74.3%, respectively, p=0.016). CONCLUSIONS: Patients treated with RP were significantly younger and had a better prognosis than patients treated using IMRT, and according to our results, RP had better outcomes in terms of OS while IMRT had greater MOC. Treatment modality did not affect the CSS.