Pediatric Urology Providers' Perceptions and Attitudes on Transitional Urologic Care in a Single-Payer Healthcare System.

INTRODUCTION: Advances in healthcare have improved outcomes for pediatric patients with congenital neuro-urological conditions, highlighting the need for an effective transition from pediatric to adult care. This study investigates Canada's transitional urologic care within its single-payer healthcare system, focusing on the active members of Pediatric Urologists of Canada's (PUC) practices, perceptions, and attitudes towards transitional urologic care. METHODS: A survey was distributed to 35 Pediatric Urologists of Canada (PUC) members from July 2023 to January 2024, which collected data on transitional care practices and available Transitional Urology (TU) clinics. It also focused on a service overview, covering aspects such as the responder's geographic and institutional affiliations, clinical practice characteristics involving transitional care, perceived challenges, and strategies for care enhancement. RESULTS: Nationwide engagement emphasized a commitment to improving transitional care, with a significant proportion of respondents (64%) having over 10 years of practice, reflecting substantial experience in addressing transitional care challenges. The survey identified 4 dedicated transitional care clinics, 3 of which are active, pointing to concerted efforts towards specialized service provision. The major challenges identified include the lack of adult transitional care initiatives and governmental support. Recommendations for improvement should focus on standardizing transition protocols and boosting patient education. The survey also underscored the necessity of protocolized care for Spina Bifida-Neurogenic Bladder and complex urogenital conditions. CONCLUSION: This study highlights the active efforts and existing challenges within Canada's transitional urologic care system, particularly emphasizing operational transitional care clinics as a crucial step forward in catering to transitioning patients' needs.

Potential effects of the discharge of wastewater treatment plant (WWTP) effluents in benthic communities: evidence from three distinct WWTP systems.

Wastewater treatment plant (WWTP) effluents can be sources of environmental contamination. In this study, we aimed to understand whether effluents of three different WWTPs may have ecological effects in riverine recipient ecosystems. To achieve this, we assessed benthic phytobenthos and macroinvertebrate communities at three different locations relative to the effluent discharge: immediately upstream, immediately downstream and 500-m downstream the effluent discharge. Two approaches were employed: the ecological status classification as defined in the Water Framework Directive (WFD) based on biological indicators; constrained multivariate analysis to disentangle the environmental drivers (physicochemical variables and contaminants, namely metals, polycyclic aromatic hydrocarbons, pharmaceuticals, and personal care products) of ecological changes across the study sites. The results showed inconsistencies between the WFD approach and the multivariate approach, as well as between the responses of macroinvertebrates and diatoms. The WWTP effluents impacted benthic communities in a single case: macroinvertebrates were negatively affected by one of the WWTP effluents, likely by the transported pharmaceuticals (other stressors are essentially homogeneous among sites). Given the findings and the scarcity of consistent evidence on ecological impacts that WWTP effluents may have in recipient ecosystems, further research is needed towards more sustainable regulation and linked environmental protection measures.

Knowledge about cervical cancer in young Portuguese women: a cross-sectional study.

Introduction: Health literacy is crucial to adherence to medical interventions in therapeutics, prevention, and diagnosis. The basis for literacy is knowledge. To accomplish the goals for the elimination of cervical cancer, one of the most prevalent and preventable cancers, we must understand the determinants of non-adherence and address them specifically to ensure patients' active participation. Aim: To determine women's knowledge regarding the manifestations of cervical cancer and its prevention. Materials and methods: We conducted a cross-sectional study in an urban population from northern Portugal. Women aged 18 to 30 years were randomly assigned to answer the Cervical Cancer Awareness Measure questionnaire, including questions of knowledge about the causes and symptoms of cervical cancer, prospecting for individual and social-related determinants. Results: The total number of participants was 270, with a mean age of 24.7 years. Knowledge about symptoms scored 5.4 ± 2.6, with a maximum of 12 points, and knowledge about the causes scored 5.7 ± 1.9, with a maximum of 11 points. The correlation between both was 0.334. High education, high socio-economic status, self-perception of one's capacity to recognize symptoms, and knowledge about the HPV vaccine were associated with better knowledge. Discussion: Portuguese women present low knowledge about cervical cancer, potentially affecting their health through exposure to risk situations and non-adherence to routine screening.

Adipose tissue rearrangement in cancer cachexia: The involvement of ß3-adrenergic receptor associated pathways.

Cancer-associated cachexia (CAC) is a complex multiple organ syndrome that significantly contributes to reduced quality of life and increased mortality among many cancer patients. Its multifactorial nature makes its early diagnosis and effective therapeutic interventions challenging. Adipose tissue is particularly impacted by cachexia, typically through increased lipolysis, browning and thermogenesis, mainly at the onset of the disease. These processes lead to depletion of fat mass and contribute to the dysfunction of other organs. The ß-adrenergic signalling pathways are classical players in the regulation of adipose tissue metabolism. They are activated upon sympathetic stimulation inducing lipolysis, browning and thermogenesis, therefore contributing to energy expenditure. Despite accumulating evidence suggesting that ß3-adrenergic receptor stimulation may be crucial to the adipose tissue remodelling during cachexia, the literature remains controversial. Moreover, there is limited knowledge regarding sexual dimorphism of adipose tissue in the context of cachexia. This review paper aims to present the current knowledge regarding adipose tissue wasting during CAC, with a specific focus on the role of the ß3-adrenergic receptor, placing it as a potential therapeutic target against cachexia.

Development of a loop-mediated isothermal amplification assay for the rapid detection of Styphnolobium japonicum (L.) Schott as an adulterant of Ginkgo biloba (L.).

BACKGROUND: Species adulteration is a concern in herbal products, especially when plant substitutes of lower economic value replace valuable botanicals. Styphnolobium japonicum is well known as a potential adulterant of Ginkgo biloba, which is one of the most demanded medicinal plants due to its wide use in pharmaceuticals, food supplements, and traditional medicine. Despite bearing some resemblance to ginkgo's flavonol composition, S. japonicum lacks many of G. biloba's desired therapeutic properties. To prevent adulteration practices, it is crucial to implement rigorous quality control measures, including fast and simple diagnostic tools that can be used on-field. PURPOSE: This study aims to develop for the first time a species-specific loop-mediated isothermal amplification (LAMP) method for the fast identification of S. japonicum in ginkgo-containing products. METHODS: A set of four specific primers (SjF3, SjB3, SjFIP, and SjBIP) and loop primers (SjLF and SjLB) were designed for a LAMP based assay using the 5.8S partial sequence and the internal transcribed spacer 2 of nuclear ribosomal DNA of S. japonicum. RESULTS: The successful amplification of the LAMP assay was inspected through visual detection, with the highest intensity recorded at the optimal conditions set at 68 °C for 40 min. The primers showed high specificity and were able to accurately discriminate S. japonicum from G. biloba and 49 other species of medicinal plants. Furthermore, the proposed LAMP assay proved to be fast, selective, and highly sensitive, as demonstrated by the absolute and relative limits of detection, which were reached at 0.5 pg for S. japonicum DNA and 0.01 % S. japonicum in G. biloba, respectively. CONCLUSIONS: This novel approach allows easy identification and discrimination of S. japonicum as a potential adulterant of G. biloba, thus being a useful tool for quality control. Compared to chromatographic or PCR-based methods, the assay proved to be fast, sensitive and did not require expensive equipment, thus offering the possibly usage in field analysis.

Should a Refluxing Internal Diversion Be Considered a Temporizing Procedure? Extended Follow-Up and Outcomes After Side-to-Side Ureterovesicostomy for Primary Obstructive Megaureter in Young Children.

PURPOSE: We describe long-term outcomes, including UTIs and need for reimplantation, after ureterovesicostomy (UV) as a lasting surgical procedure for children with primary obstructive megaureter (POM). MATERIALS AND METHODS: Children referred to our institution between 2016 and 2023 who underwent refluxing UV were analyzed. POM was defined as hydroureteronephrosis with distal ureteral dilatation > 7 mm and a negative workup for other etiologies of hydronephrosis. We assessed for surgical outcomes, complications, rate of UTI, and improvement in upper tract dilatation. Statistical analyses assessed for change in hydronephrosis metrics over follow-up. RESULTS: Among 183 patients diagnosed with POM, 47 (24%) underwent UV. Median age of presentation, surgery, and follow-up was 2, 9, and 43 months, respectively. A total of 7 patients developed 30-day complications: Clavien-Dindo grade 1 in 2 (transient urinary retention) and grade 2 in 5 (UTIs). During monitoring 14 (30%) developed UTIs and 7 (15%) required ureteral reimplant or UV takedown. After surgery there was a significant decrease in the proportion of patients with high-grade hydronephrosis, anteroposterior renal pelvis diameter, and maximum ureteral dilatation. CONCLUSIONS: Refluxing UV is a safe alternative to cutaneous diversion in POM. Most patients had improvement in upper tract dilatation with an acceptable short-term complication rate and need for reoperation (in comparison to routine later reimplantation). Our experience suggests that monitoring alone after UV is feasible, and that selective subsequent reconstruction is a reasonable strategy.

Advancing Precision Medicine: A Review of Innovative In Silico Approaches for Drug Development, Clinical Pharmacology and Personalized Healthcare.

The landscape of medical treatments is undergoing a transformative shift. Precision medicine has ushered in a revolutionary era in healthcare by individualizing diagnostics and treatments according to each patient's uniquely evolving health status. This groundbreaking method of tailoring disease prevention and treatment considers individual variations in genes, environments, and lifestyles. The goal of precision medicine is to target the "five rights": the right patient, the right drug, the right time, the right dose, and the right route. In this pursuit, in silico techniques have emerged as an anchor, driving precision medicine forward and making this a realistic and promising avenue for personalized therapies. With the advancements in high-throughput DNA sequencing technologies, genomic data, including genetic variants and their interactions with each other and the environment, can be incorporated into clinical decision-making. Pharmacometrics, gathering pharmacokinetic (PK) and pharmacodynamic (PD) data, and mathematical models further contribute to drug optimization, drug behavior prediction, and drug-drug interaction identification. Digital health, wearables, and computational tools offer continuous monitoring and real-time data collection, enabling treatment adjustments. Furthermore, the incorporation of extensive datasets in computational tools, such as electronic health records (EHRs) and omics data, is also another pathway to acquire meaningful information in this field. Although they are fairly new, machine learning (ML) algorithms and artificial intelligence (AI) techniques are also resources researchers use to analyze big data and develop predictive models. This review explores the interplay of these multiple in silico approaches in advancing precision medicine and fostering individual healthcare. Despite intrinsic challenges, such as ethical considerations, data protection, and the need for more comprehensive research, this marks a new era of patient-centered healthcare. Innovative in silico techniques hold the potential to reshape the future of medicine for generations to come.

Structural characterization of the ACDC domain from ApiAP2 proteins of the malaria parasite.

The Apicomplexan AP2 (ApiAP2) proteins are the best characterized family of DNA-binding proteins in the malaria parasite. Apart from the AP2 DNA-binding domain, there is little sequence similarity between ApiAP2 proteins and no other functional domains have been extensively characterized. One protein domain, which is present in a subset of the ApiAP2 proteins, is the conserved AP2-coincident domain mostly at the C-terminus (ACDC domain). Here we solved for the first time the crystal structure of the ACDC domain from two distinct Plasmodium falciparum ApiAP2 proteins and one orthologue from P. vivax , revealing a non-canonical four-helix bundle. Despite little sequence conservation between the ACDC domains from the two proteins, the structures are remarkably similar and do not resemble that of any other known protein domains. Due to their unique protein architecture and lack of homologues in the human genome, we performed in silico docking calculations against a library of known antimalarial compounds and we identified a small molecule that can potentially bind to any Apicomplexan ACDC domain within a pocket highly conserved amongst ApiAP2 proteins. Inhibitors based on this compound would disrupt the function of the ACDC domain and thus of the ApiAP2 proteins containing it, providing a new therapeutic window for targeting the malaria parasite and other Apicomplexans.

Recurrent IgA Nephropathy or Subclinical Chronic Humoral Rejection With Predominance of Plasma Cells: A Case Report.

Both antibody-mediated rejection and recurrence of kidney disease are major causes of allograft loss. A possible strategy to address the former is donor-specific antibody (DSA) monitoring. In this patient with IgA nephropathy, DSA detection triggered biopsy 10 years after transplant despite preserved graft function and normal urinary examination. Biopsy showed mild glomerulitis, mild capillaritis, and transplant glomerulopathy with no C4d peritubular capillary staining, along with IgA-dominant mesangial immunofluorescence staining. Interstitial inflammation had a notable predominance of plasma cells, a finding that has been variably attributed to rejection and worse prognosis. Immunosuppression was optimized with the working diagnosis of recurrent IgA nephropathy and/or chronic active humoral rejection with predominance of plasma cells, with favorable response at follow-up. This case illustrates the conflicting role of DSA monitoring and allograft biopsy to optimize immunosuppression management. Despite imperfect correlation with each other and clinical outcomes, they are key to tailor therapy. In the future, characterization of the role of plasma cell infiltrates in rejection might further enable prognosis and treatment individualization.

Establishment of Diagnostic Reference Levels in Portuguese Interventional Radiology departments.

PURPOSE: To establish Portuguese Diagnostic Reference Levels (DRLs), for six body fluoroscopy guided interventional procedures (FGIP). METHOD: A retrospective study was conducted in five interventional departments most representative of Interventional Radiology (IR) practice. Dose values, in terms of air kerma area product (PKA in Gy.cm2), air kerma at the patient entrance reference point (Ka,r in mGy), and exposure parameters (fluoroscopy time (FT) and number of cine runs) were collected. Examinations were selected per procedure (at least 20), according to the antero-posterior and lateral diameter mean value (±5 cm), measured on previous Computed Tomography (CT) examinations. RESULTS: Data of 489 body FGIP show a large variation on dose values per procedure and per department. National DRLs in terms of PKA were 20.2 Gy.cm2 for Percutaneous transhepatic biliary drainage (PTBD), 98.2 Gy.cm2 for Bronchial artery embolisation (BAE), 247.7 Gy.cm2 for Transarterial chemoembolisation (TACE), 331.6 Gy.cm2 for Inferior epigastric arteries embolisation (IEAE), 312.0 Gy.cm2 for Transjugular intrahepatic portosystemic shunt (TIPS) and 19.3 Gy.cm2 for Endovascular treatment of femoral popliteal arteries (ETFPA). CONCLUSIONS: This is the first study reporting Interventional Radiology DRLs in Portugal and we propose preliminary national estimates for the six more common body FGIP. The results of this study will be presented and discussed with all Portuguese IR departments, to promote procedures optimisation.

Amitriptyline ecotoxicity in Danio rerio (Hamilton, 1822) embryos - similar toxicity profile in the presence of nanoplastics.

Interaction of nanoplastics (NPls) with other environmental contaminants could affect their uptake by the organisms and their toxicity. Thus, the present study aims to investigate the polystyrene NPls (44 nm) interaction with the antidepressant amitriptyline (AMI) and its toxicity to Danio rerio embryos. A similar toxicological profile for NPls + AMI exposure was found for most of the evaluated endpoints, comparing with AMI single exposure, showing that the presence of NPls did not modulate the AMI toxicity. However, the behavioral assessment showed a different pattern with hypoactivity for the NPls + AMI exposure (NPls - hyperactivity; AMI - no effect). Interaction effects between NPls and AMI were also found in the protein contents (antagonism) and in the total glutathione content (synergism). This study highlights the complexity and unpredictability of NPls interaction with pharmaceuticals, important for an accurate environmental risk assessment and for the developing of effective strategies and interventions against plastic pollution.

The Toronto nomogram: A Bayesian meta-regression derived prenatal ultrasound index to predict lower urinary tract obstruction and prune belly syndrome.

INTRODUCTION: A nomogram for predicting the diagnosis of lower urinary tract obstruction (LUTO) based on an antenatal ultrasound index generated from a Bayesian Meta-regression analysis has been in development and noted with superior diagnostic accuracy compared to the keyhole sign (KHS). We aim to assess the accuracy of the nomogram in expanded diagnostic utilization to predict LUTO. METHODOLOGY: The validation of the nomogram for expanded diagnostic utilization was based on data from a prospective institutional antenatal clinic database between January 2020 and June 2022. Diagnostic accuracy indices were determined for confirmed postnatal diagnosis of LUTO or prune belly syndrome (PBS). Receiver operating characteristics (ROC) curves were generated to compare the area under the curve (AUC) of the nomogram versus KHS. RESULTS: Based on 84 male fetuses with antenatal ultrasound of moderate-severe hydronephrosis (PUV n = 15, PBS n = 4), the KHS had 26.3% (95%CI 9.1-51.2) sensitivity and 100% (95%CI 94.4%-100%) specificity, with 14 false-negatives. The nomogram showed a 84.2 (95%CI 60.4%-96.6%) sensitivity and 95.4 (95%CI 87.1%-99%) specificity with three false-positives. The nomogram also had a superior AUC compared to KHS (0.98 vs. 0.63). CONCLUSION: The nomogram can be used as a valuable tool to trigger further postnatal screening and provide individualized risk assessments to families during prenatal counseling.

A report on a survey among Portuguese Association of Interventional Cardiology associates regarding ionizing radiation protection practices in national interventional cath-labs.

INTRODUCTION AND OBJECTIVES: Concerns surrounding the consequences of ionizing radiation (IR) have increased in interventional cardiology (IC). Despite this, the ever-growing complexity of diseases as well as procedures can lead to greater exposure to radiation. The aim of this survey, led by Portuguese Association of Interventional Cardiology (APIC), was to evaluate the level of awareness and current practices on IR protection among its members. METHODS: An online survey was emailed to all APIC members, between August and November 2021. The questionnaire consisted of 50 questions focusing on knowledge and measures of IR protection in the catheterization laboratory. Results were analyzed using descriptive statistics. RESULTS: From a response rate of 46.9%, the study obtained a total sample of 159 responses (156 selected for analysis). Most survey respondents (66.0%) were unaware of the radiation exposure category, and only 60.4% reported systematically using a dosimeter. A large majority (90.4%) employed techniques to minimize exposure to radiation. All participants used personal protective equipment, despite eyewear protection only being used frequently by 49.2% of main operators. Ceiling suspended shields and table protectors were often used. Only two-thirds were familiar with the legally established limit on radiation doses for workers or the dose that should trigger patient follow-up. Most of the survey respondents had a non-certified training in IR procedures and only 32.0% had attended their yearly occupational health consultation. CONCLUSIONS: Safety methods and protective equipment are largely adopted among interventional cardiologists, who have shown some IR awareness. Despite this, there is room for improvement, especially concerning the use of eyewear protection, monitoring, and certification.

[A Cognitive Behavioural-Based Intervention in Reducing Test Anxiety in High School Students: A Pilot Cluster Randomized Controlled Trial]. / Intervenção de Base Cognitivo-Comportamental na Redução da Ansiedade Perante os Testes em Alunos do Ensino Secundário: Estudo Piloto Aleatorizado e Controlado Por Clusters.

INTRODUCTION: School-age test anxiety is an important risk factor for school performance. Notwithstanding, few studies seek to identify which strategies are effective in improving test anxiety. The aim of this study was to assess whether a cognitive-behavioural intervention for high school students could significantly reduce test anxiety. MATERIAL AND METHODS: Two-arm, cluster-randomized controlled, unblinded, parallel, trial. Participants were 10th grade students from Alves Martins High School in Viseu, Portugal. Students were randomized at class level to receive a cognitive-behavioural-based intervention combined with mindfulness, psychoeducation, and relaxation techniques, or to a control group with no intervention. Participants' anxiety levels were measured using the Test Anxiety Questionnaire. The analysis of the effect of the intervention was carried out on an intention-to-treat basis at the class level, using multilevel mixed effects models and Bayesian modelling. RESULTS: The intervention had a significant effect in reducing test anxiety (d = 0.81, 95% CI 0.45;1.17, Bayes factor = 31.3). Male gender was an independent risk factor for smaller reductions in anxiety levels. The intervention was more effective in reducing the worry component of test anxiety (d = 0.76, 95% CI 0.41;1.11, Bayes factor = 19.9) than the emotionality component (d = 0.63, 95% CI 0.31;0.95, Bayes factor = 6.6). CONCLUSION: A cognitive-behavioural intervention specifically designed to reduce test anxiety, using a combination of mindfulness, psychoeducation and relaxation techniques, was effective in reducing test anxiety levels. TRIAL REGISTRATION: Retrospectively registered on clinicaltrials.gov (NCT05481099) in 08/01/2022.

Introdução: A ansiedade face aos testes é um importante fator condicionante da performance escolar. Contudo, são escassos os estudos que procuram identificar quais as estratégias eficazes na sua melhoria. Este estudo teve como objetivo testar a eficácia de uma intervenção cognitivo-comportamental na redução da ansiedade face aos testes em alunos do ensino secundário. Material e Métodos: Estudo experimental, aleatorizado por clusters (turmas), controlado, sem ocultação, com dois grupos paralelos, com alunos do 10.º ano da Escola Secundária Alves Martins em Viseu, Portugal. Os alunos foram aleatorizados ao nível da turma para receber uma combinação de técnicas cognitivas e comportamentais, de mindfulness, psicoeducação e técnicas de relaxamento, ou para um grupo controlo sem intervenção. Os níveis de ansiedade dos participantes foram medidos através do Questionário de Ansiedade face aos Testes. A análise do efeito da intervenção foi realizada na base de intenção de tratar ao nível da turma recorrendo a modelos de efeitos mistos multinível e modelação bayesiana. Resultados: A intervenção teve um efeito significativo na redução da ansiedade face aos testes (d = 0,81, IC 95% 0,45;1,17, fator de Bayes = 31,3). Pertencer ao sexo masculino revelou-se um fator de risco independente para uma menor redução nos níveis de ansiedade. O efeito da intervenção foi mais pronunciado na redução da preocupação face aos testes (d = 0,76, IC 95% 0,41;1,11, fator de Bayes = 19,9) quando comparado com a emocionalidade (d = 0,63, IC 95% 0,31;0,95, fator de Bayes = 6,6). Conclusão: Uma intervenção especificamente desenhada para reduzir a ansiedade face aos testes, usando uma combinação de técnicas cognitivas e comportamentais de mindfulness, psicoeducação e técnicas de relaxamento, foi eficaz na redução dos níveis de ansiedade. Registo do Estudo: Estudo registado a posteriori (registo retrospetivo) em ClinicalTrials.gov com o número NCT05481099 em 01/08/2022.

The urological evaluation and management of neurogenic bladder in children and adolescents-what every pediatric nephrologist needs to know.

Neurogenic bladder (NGB) is an encompassing term that includes multiple causes of bladder dysfunction linked to a congenital or acquired neurological condition that adversely impacts the innervation of the lower urinary tract. Multiple static or progressive conditions can be associated with NGB in pediatric and adolescent patients. Currently, spinal dysraphism (i.e., spina bifida) is one of the most common etiologies, which occurs in 3-4 per 10,000 live births in developed nations. Abnormal bladder dynamics can lead to kidney damage secondary to high pressures or recurrent infections, as well as urinary incontinence. The current management paradigm centers on a proactive approach to preserving kidney function and achieving continence through behavioral, pharmacological, and surgical means. This educational review highlights the key components of urological management to maximize collaboration with pediatric nephrologists.

Trends in Management of Fetuses with Suspected Lower Urinary Tract Obstruction (LUTO): A High-Risk Fetal and Pediatric Center Experience in a Universal-Access-to-Care System.

INTRODUCTION: Neonates with lower urinary tract obstruction (LUTO) experience high morbidity and mortality associated with the development of chronic kidney disease. The prenatal detection rate for LUTO is less than 50%, with late or missed diagnosis leading to delayed management and long-term sequelae in the remainder. We aimed to explore the trends in prenatal detection and management at a high-risk fetal center and determine if similar trends of postnatal presentations were noted for the same period. METHODS: Prenatal and postnatal LUTO databases from a tertiary fetal center and its associated pediatric center between 2009 and 2021 were reviewed, capturing maternal age, gestational age (GA) at diagnosis, and rates of termination of pregnancy (TOP). Time series analysis using autocorrelation was performed to investigate time trend changes for prenatally suspected and postnatally confirmed LUTO cases. RESULTS: A total of 161 fetuses with prenatally suspected LUTO were identified, including 78 terminations. No significant time trend was found when evaluating the correlation between time periods, prenatal suspicion, and postnatal confirmation of LUTO cases (Durbin-Watson [DW] = 1.99, p = 0.3641 and DW = 2.86, p = 0.9113, respectively). GA at referral was 20.0 weeks (interquartile range [IQR] 12, 35) and 22.0 weeks (IQR 13, 37) for TOP and continued pregnancies (p < 0.0001). GA at initial ultrasound was earlier in terminated fetuses compared to continued (20.0 [IQR 12, 35] weeks vs. 22.5 [IQR 13, 39] weeks, p < 0.0001). While prenatal LUTO suspicion remained consistently higher than postnatal presentations, the rates of postnatal presentations and terminations remained stable during the study years (p = 0.7913 and 0.2338), as were GA at TOP and maternal age at diagnosis (p = 0.1710 and 0.1921). CONCLUSION: This study demonstrated that more severe cases of LUTO are referred earlier and are more likely to undergo TOP. No significant trend was detected between time and prenatally suspected or postnatally confirmed LUTO, highlighting the need for further studies to better delineate factors that can increase prenatal detection.

DNA-Targeted Complexes of Tc and Re for Biomedical Applications.

Due to their favorable chemical features, Re and Tc complexes have been widely used for the development of new therapeutic agents and imaging probes to solve problems of biomedical relevance. This review provides an update of the most relevant research efforts towards the development of novel cancer theranostic agents using Re and Tc-based compounds interacting with specific DNA structures. This includes a variety of homometallic complexes, namely those containing M(CO)3 (M=Re, Tc) moieties, that exhibit different modes of interaction with DNA, such as covalent binding, intercalation, groove binding or G-quadruplex DNA binding. Additionally, heterometallic complexes, designed to potentiate synergistic effects of different metal centers to improve DNA-targeting, cytotoxicity and fluorescence properties, are also reviewed. Particular attention is also given to 99m Tc- and 188 Re-labeled oligonucleotides that have been widely explored to develop imaging and therapeutic radiopharmaceuticals through the in vivo hybridization with a specific complementary DNA or RNA target sequence to provide useful molecular tools in precision medicine for cancer diagnosis and treatment. Finally, the need for further improvement of DNA-targeted Re and Tc-based compounds as potential therapeutic and diagnostic agents is highlighted, and future directions are discussed.

Synthesis and Preclinical Evaluation of PSMA-Targeted 111In-Radioconjugates Containing a Mitochondria-Tropic Triphenylphosphonium Carrier.

Nuclear DNA is the canonical target for biological damage induced by Auger electrons (AE) in the context of targeted radionuclide therapy (TRT) of cancer, but other subcellular components might also be relevant for this purpose, such as the energized mitochondria of tumor cells. Having this in mind, we have synthesized novel DOTA-based chelators carrying a prostate-specific membrane antigen (PSMA) inhibitor and a triphenyl phosphonium (TPP) group that were used to obtain dual-targeted 111In-radioconjugates ([111In]In-TPP-DOTAGA-PSMA and [111In]In-TPP-DOTAGA-G3-PSMA), aiming to promote a selective uptake of an AE-emitter radiometal (111In) by PSMA+ prostate cancer (PCa) cells and an enhanced accumulation in the mitochondria. These dual-targeted 111In-radiocomplexes are highly stable under physiological conditions and in cell culture media. The complexes showed relatively similar binding affinities toward the PSMA compared to the reference tracer [111In]In-PSMA-617, in line with their high cellular uptake and internalization in PSMA+ PCa cells. The complexes compromised cell survival in a dose-dependent manner and in the case of [111In]In-TPP-DOTAGA-G3-PSMA to a higher extent than observed for the single-targeted congener [111In]In-PSMA-617. µSPECT imaging studies in PSMA+ PCa xenografts showed that the TPP pharmacophore did not interfere with the excellent in vivo tumor uptake of the "golden standard" [111In]In-PSMA-617, although it led to a higher kidney retention. Such kidney retention does not necessarily compromise their usefulness as radiotherapeutics due to the short tissue range of the Auger/conversion electrons emitted by 111In. Overall, our results provide valuable insights into the potential use of mitochondrial targeting by PSMA-based radiocomplexes for efficient use of AE-emitting radionuclides in TRT, giving impetus to extend the studies to other AE-emitting trivalent radiometals (e.g., 161Tb or 165Er) and to further optimize the designed dual-targeting constructs.

Pathological Findings in Fetuses Terminated for Suspected Lower Urinary Tract Obstruction: Experience From a High-Risk Fetal Center in Canada.

PURPOSE: Pregnancies complicated by prenatally suspected lower urinary tract obstruction (LUTO) can be associated with high rates of terminations due to potentially poor outcomes. Herein, we assessed autopsy findings of fetuses terminated for suspected LUTO to evaluate the prenatal diagnostic accuracy and spectrum of underlying pathologies. MATERIALS AND METHODS: We performed a retrospective review of all pregnancies referred to a high-risk fetal center in a universal access to care health care system for suspected LUTO that opted for termination of pregnancy between 2009 and 2022. Ultrasound features, genetic investigations, placental findings, and distribution of postmortem diagnoses were assessed. RESULTS: Of a total of 190 pregnancies with suspected LUTO evaluated during the study period, 79 (42%) were terminated. We excluded 35 fetuses with incomplete data, resulting in 44 available for analysis. Pregnancies were terminated at a mean gestation of 22 ± 5 weeks. A LUTO diagnosis was confirmed in 37 (84.1%) fetuses (35 males, 2 females), and the remaining 7 showed other pathologies. Pulmonary hypoplasia was found in 62.2% (n = 23) and placental pathologies in 56.8% of confirmed LUTO compared to 33.4% and 71.4% in non-LUTO cases, respectively. Overall, a total of 31 fetuses underwent additional prenatal investigations with genetic anomalies detected only in fetuses with a confirmed LUTO diagnosis (13.6%). CONCLUSIONS: In our health care system, almost half of prenatally suspected LUTO pregnancies are terminated. The sonographic diagnostic accuracy for LUTO is reasonable at 84%. However, the remaining 16% still had significant pathologies. Genetic abnormalities are uncommon and rarely the trigger for pregnancy terminations.