The article aims to find potential biomarker for the detection of tubular damage in pediatric neurogenic bladder (NB) by investigating urinary levels of liver-type fatty acid-binding protein (uL-FABP). This prospective analysis was conducted on two groups: 42 children with NB and 18 healthy children. The uL-FABP concentrations were measured using ELISA methods. The children’s medical charts were analyzed to determine age, sex, anthropometric measurements, activity assessment using Hoffer’s scale and renal function parameters. The results revealed that the uL-FABP/creatinine ratio was higher in the studied group compared with the reference group. A significant positive correlation between uL-FABP and proteinuria was found. Children with a history of vesicoureteral reflux (VUR) tended to have elevated uL-FABP. In conclusion, uL-FABP may be considered a potential tubular damage biomarker in children with NB. Proteinuria and history of VUR may be the factors influencing uL-FABP.

Background: Estrogen homeostasis is crucial for bladder function, and estrogen deprivation resulting from ovarian removal or ovarian dysfunction may lead to various bladder dysfunctions. However, the specific mechanisms are not fully understood. Methods: We simulated estrogen deprivation using a rat ovariectomy model and supplemented estrogen through subcutaneous injections. The metabolic characteristics of bladder tissue were analyzed using non-targeted metabolomics, followed by bioinformatics analysis to preliminarily reveal the association between estrogen deprivation and bladder function. Results: We successfully established a rat model with estrogen deprivation and, through multivariate analysis and validation, identified several promising biomarkers represented by 3, 5-tetradecadiencarnitine, lysoPC (15:0), and cortisol. Furthermore, we explored estrogen deprivation-related metabolic changes in the bladder primarily characterized by amino acid metabolism imbalance. Conclusions: This study, for the first time, depicted the metabolic profile of bladder resulting from estrogen deprivation, providing an important experimental basis for future research on bladder dysfunctions caused by estrogen deprivation.

Bladder cancer (BC) diagnosis is reliant on cystoscopy, an invasive procedure associated with urinary tract infections. This has sparked interest in identifying non-invasive biomarkers in body fluids such as blood and urine. A source of biomarkers in these biofluids are extracellular vesicles (EVs), nanosized vesicles that contain a wide array of molecular cargo, including small non-coding RNA such as microRNA and transfer RNA-derived fragments (tRF). Here we performed small-RNA next-generation sequencing for urine EVs, serum EVs and serum supernatant from 41 patients with non-muscle invasive BC (27 stage Ta, 14 stage T1) and 15 non-cancer patients (NCP) with benign cystoscopy findings. Serum and urine samples were collected before transurethral resection of bladder tumors (TUR-b) and at routine postsurgery check-ups. Expression levels of tRFs in presurgery samples were compared to those at postsurgery check-ups and to NCPs. To strengthen the reliability of our results, samples from 10 patients with stage T1 disease were resequenced. When comparing tRF expression in urine EVs between BC patients with stage T1 disease and NCPs, 14 differentially expressed tRFs (DEtRFs) were identified. In serum supernatant, six DEtRFs were identified among stage T1 patients when comparing presurgery to postsurgery samples, and four DEtRFs were found when comparing presurgery samples to NCPs. By performing a blast search, we found that sequences of DEtRFs aligned with genomic sequences pertaining to processes relevant to cancer development, such as enhancers, regulatory elements and CpG islands. Our findings display a number of tRFs that may hold potential as biomarkers for the diagnosis and recurrence-free survival of BC.

One of the most common complications of neurogenic bladder secondary to spinal cord injury (SCI) is urinary incontinence, possibly related to bladder-emptying methods and changes in quality of life. This study aimed to identify the occurrence of this complication in adults with SCI and analyze its relationship with bladder-emptying methods, satisfaction, and lifestyle. This is a quantitative, exploratory, cross-sectional study. The variables were collected using the Bowel and Bladder Treatment Index during a telephone interview with 290 participants from February to November 2021. According to the results, 70% of the participants were male and 74.1% performed clean intermediate catheterization (CIC) as the main bladder-emptying method. Moreover, 55.6% were considered incontinent in the last year. Emptying by normal urination and bladder reflex triggering had a statistically significant relationship with urinary incontinence. A statistical association was observed between all the variables of satisfaction and lifestyle with urinary incontinence. Although CIC reduced urine leakage, a considerable number of participants still presented with frequent urine leakage. Urinary incontinence negatively altered satisfaction with the bladder-emptying method, effectiveness of bladder management, quality of life, and personal and social relationships.

Urinary tract diseases are common in cats, and often require surgical reconstruction. Here, to explore the possibility of urinary tract reconstruction in cats using in-vivo tissue architecture (iBTA), biosheets fabricated using iBTA technology were implanted into the feline bladder and the regeneration process was histologically evaluated. The biosheets were prepared by embedding molds into the dorsal subcutaneous pouches of six cats for 2 months. A section of the bladder wall was removed, and the biosheets were sutured to the excision site. After 1 and 3 months of implantation, the biosheets were harvested and evaluated histologically. Implantable biosheets were formed with a success rate of 67%. There were no major complications following implantation, including tissue rejection, severe inflammation, or infection. Urinary incontinence was also not observed. Histological evaluation revealed the bladder lumen was almost entirely covered by urothelium after 1 month, with myofibroblast infiltration into the biosheets. After 3 months, the urothelium became multilayered, and mature myocytes and nerve fibers were observed at the implantation site. In conclusion, this study showed that tissue reconstruction using iBTA can be applied to cats, and that biosheets have the potential to be useful in both the structural and functional regeneration of the feline urinary tract.

Background: Despite a range of available treatments, there is a remaining unmet need for patients with severe post-partum hemorrhage (sPPH). Objective: This manuscript evaluated efficacy and safety of recombinant activated factor VIIa (rFVIIa) in sPPH management. Methods: An open-label, multi-center, randomized controlled trial (RCT; NCT00370877) and four observational studies (OS; OS-1 [NCT04723979], OS-2, OS-3 and OS-4) were analyzed regarding efficacy (need for subsequent invasive procedures, including uterine compression sutures, uterine or iliac artery ligation, arterial embolization or hysterectomy) and safety (incidence of thromboembolic events [TE] and maternal mortality) of rFVIIa for sPPH. The RCT, and OS-1 and OS-2, included a control group of women who did not receive rFVIIa (with propensity score-matching used in OS-1 and OS-2), whereas OS-3 and OS-4 provided descriptive data for rFVIIa exposed women only. Results: A total of 446 women exposed to rFVIIa and 1,717 non-exposed controls were included. In the RCT, fewer rFVIIa exposed women (50% [21/42]) had an invasive procedure versus non-exposed women (91% [38/42]; odds ratio 0.11, 95% confidence interval 0.03–0.35). In OS-1, more rFVIIa exposed women (58% [22/38]) had an invasive procedure versus non-exposed women (35% [13.3/38]; odds ratio 2.46, 95% confidence interval 1.06–5.99). In OS-2, 17% (3/18) of rFVIIa exposed women and 32% (5.6/17.8) of non-exposed women had an invasive procedure (odds ratio 0.33, 95% confidence interval 0.03–1.75). Across all included women, TEs occurred in 1.5% (0.2% arterial and 1.2% venous) of rFVIIa exposed women and 1.6% (0.2% arterial and 1.4% venous) of non-exposed women with available data. Conclusions: The positive treatment effect of rFVIIa in the RCT was not confirmed in the OS. However, the safety analysis did not show any increased incidence of TEs with rFVIIa treatment.

Dengue virus an arbovirus is endemic in an area that comprise almost half of the world's population, contrary to past beliefs that dengue virus differentiate from other neuroinvasive arbovirus due to its lack of neurological invasion and disease related neurological complications excluding hemorrhagic and thromboembolic , the body of evidence have grown to demonstrate a series of neurological manifestations linked to dengue virus with possible mechanisms involving direct virus invasion of the nervous system or immune mediated complications. In this review we provide a wide approach to this neglect but not so rare manifestations of a very common disease.

Introduction: Hypertension is a serious public health problem in Morocco. The objective of this pilot study was to estimate the salt intake of Moroccan adults by measuring 24-hour urinary sodium excretion. Methods: 132 participants were recruited from the central region of Morocco. Sodium, potassium and creatinine levels were measured using the 24-hour urine samples. Additional data included anthropometric measurements and socio-demographic questionnaire. Results: The daily sodium, potassium and creatinine excretions were 2779.1±1334.9 mg, 1350.0±642.8 mg and 820.3 ± 381.2 mg, respectively. Data analysis revealed that 71.2% of the participants had a daily sodium intake more than 2000 mg (5g of salt) recommended by the WHO. The mean of potassium excretion was 1350.0±642.8 mg /day, this average was lower than 3.51g per day recommended by the WHO. Conclusion: Public health measures to reduce sodium and increase potassium consumption in order to decrease the population’s risk of high blood pressure and heart disease are recommended.

(1) Background: Although diagnostic criteria for massive hemorrhage with organ dysfunction such as disseminated intravascular coagulation associated with delivery have been empirically established based on clinical findings, strict logic has yet to be used to establish numerical criteria. (2) Methods: A dataset of 107 deliveries with ≥2,000 g of blood loss, among 13,368 deliveries from nine national perinatal centers in Japan between 2020 and 2023 was obtained. Twenty-three patients had fibrinogen levels <170 mg/dl, which is the initiation of coagulation system failure per our previous reports. Three of these patients had hematuria. We used six machine learning methods to identify the borderline criteria dividing the fibrinogen/fibrin/fibrinogen degradation product (FDP) planes, using 15 coagulation fibrinolytic factors. (3) Results: The boundaries of hematuria development on a two-dimensional plane of fibrinogen and FDP were obtained. If the FDP–fibrinogen/3–60 (mg/dl) value is positive, this indicates hematuria; otherwise, the case is non-hematuria, as demonstrated by the support vector machine method that seemed the most appropriate. (4) Conclusions: The borderline criterion dividing the fibrinogen/FDP plane for patients with hematuria that could be considered organ dysfunction in massive hemorrhage during delivery was obtained using artificial intelligence, and this method seemed to be useful.

Subarachnoid hemorrhage (SAH) is most commonly seen in patients over 55 years of age and often results in a loss of many productive years. SAH has a high mortality rate, and sur-vivors often suffer from early and secondary brain injuries. Understanding the pathophysiology of the SAH is crucial to identifying potential therapeutic agents. One promising target for diagno-sis and prognosis of SAH is circulating microRNAs, which regulate gene expression and are in-volved in various physiological and pathological processes. In this review, we discuss the poten-tial of microRNAs as a target for diagnosis, treatment, and prognosis in SAH.

The overwhelming majority of bladder cancers are transitional cell carcinomas. Albeit mostly monotonous, carcinomas in the bladder may occasionally display a broad spectrum of histological features that should be recognized by pathologists because some of them represent a diagnostic problem and/or lead prognostic implications. Sometimes these features are focal in the context of conventional transitional cell carcinomas, but some others are generalized across the tumor making its recognition a challenge. For practical purposes, the review distributes the morphologic spectrum of changes in architectural and cytological. So, nested and large nested, micropapillary, myxoid stroma, small tubules and adenoma nephrogenic-like, microcystic, verrucous, and diffuse lymphoepithelioma-like, on one hand, and plasmacytoid, signet ring, basaloid-squamous, yolk-sac, trophoblastic, rhabdoid, lipid/lipoblastic, giant, clear, eosinophilic (oncocytoid), and sarcomatoid, on the other, are revisited. Key histological and immunohistochemical features useful in the differential diagnosis are mentioned. In selected cases, molecular data associated with the diagnosis, prognosis, and/or treatment are also included.

Intracranial hemorrhage is a serious medical problem that requires rapid and often intensive medical care. Identifying the location and type of any hemorrhage present is a critical step in the treatment of the patient. Diagnosis requires an urgent procedure, and the detection of hemorrhage is a difficult and time-consuming process for human experts. In this paper, we propose methods based on EfficientDet’s deep-learning technology that can be applied to the diagnosis of hemorrhages and thus become a decision-support system. Our proposal is two-fold. On the one hand, the proposed technique classifies slices of computed tomography scans for the presence hemorrhage or its lack, achieving 92.7% accuracy and 0.978 ROC-AUC. On the other hand, our methodology provides visual explanations of the classification chosen using the Grad-CAM methodology.

Chemoradiation-based bladder preservation therapy (BPT) is currently a curative option for non-metastatic muscle-invasive bladder cancer (MIBC) patients at favorable risk or an alternative to radical cystectomy (RC) for those who are unfit for RC. In BPT, only patients who achieve complete response (CR) after chemoradiation have favorable prognosis and quality of life with preserved functional bladder. Thus, predicting CR and favorable prognosis is important for optimal patient selection for BPT. We reviewed biomarkers for predicting clinical outcomes of chemoradiation-based BPT. Biomarkers studied were categorized into those related to apoptosis, cell proliferation, receptor tyrosine kinases, DNA damage response genes, hypoxia, molecular subtype, and others. Among these biomarkers, Ki-67 labeling index (Ki-67 LI) and meiotic recombination 11 may be used for selecting BPT or RC. Ki-67 LI and erythroblastic leukemia viral oncogene homolog 2 (erbB2) may be used for predicting both chemoradiation response and prognosis of patients on BPT. Concurrent use of trastuzumab and a combination of carbogen and nicotinamide can overcome chemoradiation resistance conferred by erbB2 overexpression and tumor hypoxia. Further studies are needed to confirm the practical utility of these biomarkers for progress on biomarker-directed personalized management of MIBC patients.

Most neurodegenerative diseases, including Alzheimer's disease, ischemic stroke, subarachnoid hemorrhage, and intracerebral hemorrhage are associated with inflammation. Tumor necrosis factor (TNF) is a pleiotropic pro-inflammatory cytokine that regulates cerebral infarction in stroke pathology, and its action is influenced by the bioavailability of its membrane-bound receptors, TNFR1 and TNFR2, and microglial activation. During the initial onset of these diseases, the soluble variant of the cytokine presents with prolonged and excessive activation of TNFR1, resulting in cell death and long-term neurological impairments. Therapeutic interventions for neurodegenerative diseases have targeted TNF to limit the onset of neuroinflammation. First-generation therapeutics have been demonstrated to inhibit membrane-bound TNF to TNFR2 receptor binding, resulting in severe side effects such as infections and cancer. As such, second-generation drugs, including XPro1595, have been developed to selectively inhibit soluble TNF and impede the effects of TNFR1 while still allowing for TNFR2 activation. Early results in murine TBI models demonstrate reduced glial reactivity by 50%, reduced dendritic degeneration by 30%, increased plasticity by 15%, and improved functional outcomes by 20% post-TBI. This scoping review of TNF receptors in various neurodegenerative diseases seeks to evaluate current and future therapeutic strategies as well as highlight potential strategies to eliminate confounding variables present in the current literature.

Keywords: FTY720, self-assembled nanoparticles, intracerebral hemorrhage, neuroprotection

Bladder cancer (BC) possesses distinct molecular profiles that influence progression depending on its biological nature and delivered treatment intensity. Muscle-invasive BC (MIBC) and non-MIBC (NMIBC) demonstrate great intrinsic heterogeneity regarding different prognoses, survival, progression, and treatment outcomes. Transurethral resection of bladder tumor (TURBT) is the standard of care in treating NMIBC and serves both diagnostic and therapeutic purposes, despite the prevalent recurrence and progression among many patients. In particular, flat urothelial car-cinoma in situ and urothelial carcinoma with lamina propria invasion are the major precursors of MIBC. A new‐generation photosensitizer, 5‐Aminolevulinic acid (5-ALA), demonstrates high tumor specificity by illuminating the tumor lesion with a specific wavelength of light to produce fluorescence, and has been studied for photodynamic diagnosis to detect precise tumor areas by TURBT. Additionally, it has been applied for treatment by producing its cytotoxic reactive oxygen species, as well as screening for urological carcinomas by excreting porphyrin in the blood and urine. Moreover, 5-ALA may contribute to screening before and after TURBT in NMIBC. Here, we summarize the updated evidence and ongoing research on photodynamic technology for NMIBC, providing insight into the potential for improving patient outcomes.

Human urinary bladder cancer has similar development that invasive urothelial cancer that happens spontaneously in dogs. Then, research of these malignant tumors associated with the advances of new treatment drive to the specific fight of the urothelial tumor cell, is highly valuably related to efficiency and reduction of side effects of treatments, even extrapolating to humans. Thus, a review of the most important aspects on new advances on canine bladder cancer was achieved. Many forms of therapies are being reported; one of them, of highly promising feature is the treatment with immunomodulators. The resemblance between spontaneous urothelial cancer in canines and urinary bladder cancer in humans makes this canine tumor relevant animal model to research and advances of treatment that may be more efficient in management of tumor with less unfavorable effects. Immunomodulators exhibit important outcomes when used in the therapy of bladder cancer in dogs. Nanomaterials that are possible carriers of some kinds of drugs to the target tumor significantly raise the efficiently of the therapy. Therefore, the advancement of immunomodulator combined with nanoparticles can disrupt the therapy of bladder cancer in dogs and thereafter in humans.

Carbapenem antibiotics are the drug of choice for treating multidrug-resistant bacterial infections. Metallo-beta-lactamases (MBLs) are carbapenemase capable of hydrolyzing nearly all therapeutically available beta-lactam antibiotics. Consequently, a need to assess the frequency and phenotypic resistance phenomena of two MBL genes in diarrheal and urinary tract infections (UTIs). Samples were collected through a cross-sectional study, with MBLs genes detected via PCR. Two hundred twenty eight diarrheal bacteria were isolated from 240 samples. The most predominant pathogens were Escherichia coli (32%) and Klebsiella spp. (7%). Phenotypic resistance to amoxicillin-clavulanic acid, aztreonam, cefuroxime, cefixime, cefepime, imipenem, meropenem, gentamicin, netilmicin, and amikacin was 50.4%, 65.6%, 66.8%, 80.5%, 54.4%, 41.6%, 25.7%, 41.2%, 37.2%, and 42.9%, respectively.  Total 142 UTI pathogens were obtained from 150 urine samples, with Klebsiella spp. (39%) and Escherichia coli (24%) are the major pathogens. Phenotypic resistance to amoxycillin-clavulanic acid, aztreonam, cefuroxime, cefixime, cefepime, imipenem, meropenem, gentamicin, netilmicin, and amikacin was 93.7%, 75.0%, 91.5%, 93.7%, 88.0%, 72.5%, 13.6%, 44.4%, 71.1%, and 43%, respectively.  Twenty four diarrheal isolates carried either blaNDM-1 or blaVIM genes; the overall MBL gene prevalence was 10.5%. Thirty six UTI pathogens carried either blaNDM-1 or blaVIM genes (25.4%). Seven isolates carried both blaNDM-1 and blaVIM genes.  MBL genes exhibited a strong association with phenotypic carbapenem and other beta-lactam antibiotic resistance. Resistance to carbapenems requires active surveillance and stewardship.

Objective: Urinary catheters are known cause of urinary morbidities. The longer the catheter is retained, the greater the risk for contamination and infection. An increasing body of literature suggests routine practice of catheterization and retaining it for 24 hours does not add any procedural advantage. Thus, we sought to study outcomes in relation to early vs. delayed removal of urinary catheters following cesarean section. Methods: We randomly assigned 116 patients into early and delayed removal of urinary catheter groups. In the early group, catheter was removed immediately after the procedure and in the delayed removal group, catheter was removed 24 hours later. Clinical outcomes were measured in terms of significant bacteriuria 72 hours postop, voiding difficulties, urinary retention, mobilization time, length of hospital stay, and patient satisfaction. Results: Study revealed higher incidence of bacteriuria in the delayed removal group (32.8% vs. 15.5%, P = 0.030). Urinary frequency was also higher (34.6% Vs. 8.6%, P=0.001). However, there were no difference between the two groups in other urinary complaints including dysuria and urgency (P = 0.103 & P = 0.087). Urinary retention was more frequent in the early group, but difference was not significant (P = 0.080). Patients with immediate removal of the urinary catheter had early ambulation and early discharge from hospital (P = 0.001 and P = 0.040) and were generally satisfied with the procedure (P= 0.010). Conclusion: Our study showed that immediate removal of urinary catheter was associated with lower urinary complications, shorter length of hospitalization and associated cost.

(1) Background: Intravesical Chemotherapy is standard of care in intermediate risk non-muscle-invasive bladder cancer (NMIBC). Different agents are used across the world based on availability, cost and practice patterns. Epirubicin (EPI), one of these agents is used by many centers over many decades. However, its true differential efficacy compared to other agents and its tolerability is still poorly reported. We aimed to assess the differential efficacy and safety of intravesical EPI in NMIBC patients. (2) Methods: A systematic search of PUBMED, Webofscience, clinicaltrials.gov, and Google Scholar databases was performed on December 31, 2023. We reviewed 28 studies that included patients treated EPI after TURBT (transurethral resection of bladder tumors) for NMIBC and who compared oncological outcomes such as recurrence and progression to other adjuvant treatment such as Mitomycin C (MMC), Gemcitabine (GEM) and BCG. Further, we looked at the safety profile of EPI at room temperature under hyperthermia intravesically and at the oncological outcomes when administrated with hyperthermia; (3) Results: When compared to other chemotherapeutics (MMC/GEM), EPI seemed to be equally effective; however, EPI seems less effective in preventing disease management recurrence compared to BCG intravesical. The most common adverse events of EPI include cystitis, dysuria, and pollakiuria. (4) Conclusions: EPI exhibits similar oncological performances to Gemcitabine and Mitomycin C currently used for adjuvant therapy in NMIBC. Novel delivery mechanisms such as hyperthermia are promising newcomers.

BackgroundIntracranial hemorrhage (ICH) in pregnancy, estimated at 1 in 10,000 cases, presents significant diagnostic challenges prenatally despite advanced imaging techniques such as ultrasound (US) and MRI. Detecting ICH is crucial for pregnancy management and future treatment decisions aimed at improving fetal survival and reducing brain damage. This report presents the diagnosis and outcomes of two cases of prenatal ICH.Cases presentationThe first case involves a 30-year-old pregnant woman with irregular prenatal care diagnosed with ICH at 32 weeks of gestation via US and MRI. She chose to continue the pregnancy, delivering a 3160g male infant at 36 weeks via cesarean section. Following NICU care including resuscitation and ventriculoperitoneal shunt placement, the infant was discharged. Subsequent examinations showed a reduction in ventricle size. In the second case, a 27-year-old woman taking acenocoumarol for a mechanical heart valve developed fetal subdural hemorrhage detected by US and MRI. She opted to terminate the pregnancy, resulting in a stillborn male infant weighing 1530g.ConclusionFetal ICH presents with varying severity and prognostic implications, diagnosed and graded using US. Fetal cranial MRI may help clarify the etiology. Management remains controversial, with termination of pregnancy potentially warranted in severe cases due to poor prognosis. Further research is needed to refine management and improve outcomes in fetal ICH.

1. Background and Objective: Spontaneous Intracranial Hemorrhage (ICH) is a catastrophic medical condition associated with significant morbidity and mortality. As the accumulation of unbound iron following ICH contributes to secondary brain injury, deferoxamine, an approved chelation drug, has become the center of attention. At the same time, its therapeutic remains a matter of dispute. This double-blinded Randomized Controlled Trial (RCT) aims to investigate the therapeutic potential of deferoxamine in neurological and radiological aspects. 2. Methods and Materials: The study enrolled 42 participants diagnosed with spontaneous ICH and confirmed by CT scan, randomly assigning them to either the deferoxamine treatment group or the placebo control group. While the control group received the routine treatment plus a placebo, the treatment group received routine treatment conjugated with 7.5 mg/kg of deferoxamine per hour intravenously over the first three days. The study compared hematoma and edema volume, GCS score, and mortality rates between the two groups. Our study employed rigorous randomization and blinding procedures to ensure unbiased results. 3. Results: There was a significant (p<0.05) improvement in patients' GCS up until the fourth day, but no significant difference was noted afterward. In addition, the volume of both edema and hematoma was significantly lower in the intervention group, as well as the length of stay, intubation requirement, and mortality. 4. Discussion: Deferoxamine administration can, at least in a short timeframe, improve neurological and radiological parameters.

Stress urinary incontinence (SUI) influences the quality of life of women. The research applied ICIQ LUTS qol (The International Consultation Incontinence Questionnaire Lower Urinary Tract Symptoms quality of life) as a tool to measure the quality of life (QOL) of patients with stage 1 SUI in many areas. 140 perimenopausal women who participated in a urodynamic test at Department of Gynecology, Endocrinology and Gynecologic Oncology, Pomeranian Medical University, Police, Poland in the years 2013-2015 were enrolled in the study. Patients were divided into two groups: A and B. Two questionnaires were applied: the author’s original questionnaire and the standardized ICIQ LUTS qol. Gymnastic plans were recommended 4 times per week for the period of 3 months. The plan for group A included the exercises of pelvic floor muscles (PFM) with the simultaneous tension of the transverse abdominal muscle (TrA) and for group B included the exercises of PMF without TrA. The evaluation of the quality of life of patients with stage 1 SUI with the use of ICIQ LUTS qol among patients from groups A and B after therapy showed a significant improvement in most areas. More impact is observed in the physiotherapy of both PFM with TrA.

Abstract We aim to describe the diagnosis and surgical management of urinary tract endometriosis (UTE). We detail current diagnostic tools including advanced transvaginal ultrasound, magnetic resonance imaging, and surgical diagnostic tools such as cystourethroscopy. While discussing surgical treatment options, we emphasize the importance of an interdisciplinary team, for complex cases that involve the urinary tract. While bladder DE is more straightforward in its surgical treatment, ureteral DE requires a high level of surgical skill. Specialists should be aware of the important entity of UTE due to the serious health implications for women. When UTE exists, it is important to work within a interdisciplinary radiological and surgical team.

Introduction: Intraventricular Hemorrhage (IVH) is a devastating condition mostly in preterm infants at < 30 weeks GA with large morbidities and mortality usually in the first 72 hours after birth. Prevention seems to be the only way to completely deal with this problem. The IVH prevention in this age group has been studied and includes some strategies such as prenatal corticosteroids, cesarean delivery, careful extraction among others, but still, it has an unacceptably high incidence in this population. A protocol with the name Drive to Zero IVH Prevention Project that was presented in one of EpicLatino conferences some years ago. As with any quality improvement in practices, we adapted this project to our unit. Objective: To compare the IVH incidence in our unit after the protocol implementation with and historic cohort from the same unit and with all other units un the epilactino network. Material and method: In October 2017 we begun to implement a neuro protection protocol. For this analysis we include every patient born <30 weeks of GA, inborn or outborn but less than 2 days old, that survived at least three days and had a neuroimaging preformed. We include cases until July 2022, and we use the EpicLatino, a Latin-American database, from 2018 to 2020 excluding our own unit for comparison as well as an historical cohort from our unit from 2010-2017. The protocol consists of: Minimal manipulation, low volume ventilation, one routine fiscal exam a day, neutral head position, one blood pressure measured per shift, no keel stick measurements, continuous dim light and low noise level, minimal touch, no vasoactive therapy except in extreme cases, temperature and humidity at 80%, catheters, when possible, fluid restriction followed with diuresis, no PDA therapy or Echo if possible and routine therapy with hydrocortisone, erythropoietin, caffeine, parenteral nutrition, and trophic feeding. e performed a univariate analysis for IVH and groups and a logistic regression model with variables that had statistical significance in the univariate analysis. Results: The study group included 64 cases, the historic cohort 123 and the EpicLatino 1029. Demographic characteristics were similar with few statistically significant differences. We found four grade 1-2 and six grade 3-4 IVH in the study group (some caused by very traumatic delivery with multiples hematomas in head, body, and extremities), all significantly lower that the other two groups. The logistic regression model confirmed the independent statistically significant result in the study group. Conclusion: The hemorrhage during delivery must be prevented by the obstetric team. Afterwards, a set of interventions like very gentle handling with minimal manipulation and unnecessary strict lab managing seams to decrease the incidence of IVH.

Sarcopenia, the degenerative and systemic loss of skeletal muscle mass, indicates patient frailty and impaired physical function. Sarcopenia can be caused by multiple factors, including advanced age, lack of exercise, poor nutritional status, inflammatory diseases, endocrine diseases, and malignancies. Recently, growing evidence has indicated the importance of sarcopenia in the management of patients with various cancers. Sarcopenia is associated with not only higher rates of treatment-related complications but also worse prognosis in cancer-bearing patients. In this article, we conducted a systematic literature review regarding the significance of sarcopenia as a prognostic biomarker of bladder cancer. We also reviewed recent studies focusing on the prognostic role of changes in skeletal muscle mass during the course of treatment in bladder cancer patients.

Urinary infections are very prevalent in pregnant women and are a cause for great concern con-sidering the negative impacts they can have on both, the mother and the baby. The objectives were characterize urinary infections associated with pregnant women, study the most prevalent strains in urinary infections in pregnant women and analyze the antibiogram of the most prevalent strains in infections in pregnant women. A retrospective observational study was carried out on all posi-tive urine cultures from pregnant women between January 2018 and December 2022 at a Hospital Center in the Center of Portugal, totaling 201 samples. Data were collected with computer support, including age, origin, previous antibiotic therapy, catheterization, isolated bacteria and tested an-tibiotic therapy. The majority of pregnant women were in the third trimester of pregnancy and came from the External Consultation. The most identified bacteria was Escherichia coli, followed by Streptococcus agalactiae. Regarding the interaction with antibiotics, Escherichia coli showed total sensitivity to one antibiotic, while Streptococcus agalactiae showed sensitivity to four anti-biotics in 2022. This work contributes to the knowledge of urinary infections in pregnant women in the center of the country, being a contribution to the continued improvement of the care provided

Urinary tract infections (UTIs) remain one of the most important problems of modern urology and medicine. Infections bring great discomfort and significantly reduce the quality of life. UTIs rank second after respiratory tract infections in outpatients. The most common pathogen of UTI are E.coli. The study of the etiology of UTI has great clinical and epidemiological importance in routine practice. Objective: To assess the etiological significance of pathogens in the occurrence of urinary tract infections in the Karaganda region of Kazakhstan. Methods: A total of 2378 patients presenting UTIs were enrolled and each provided a urine sample. The study was carried out in the Clinical Microbiology Laboratory MediTEC-NS between 2 January and 29 December 2018. Identification of isolated microorganisms was carried out on a WalkAway 96 Plus microbiological analyzer, Microscan model manufactured by Beckman Coulter (USA). Statistical Analysis was performed using the STATISTICA-6 package. Results: Out of 2378 patients a total of 1177 (49,5%) urine samples tested positive by culture test. From these samples, 1356 strains of microorganisms were isolated, of which 84.79% were monoculture and 21% were of a mixed culture. Gram-positive bacteria 690 (50, 88%), Gram-negative bacteria 630 (46, 46%), and Candida 36 (2.65%) were identified. Gram-negative rods were represented by Enterobacterales 557 (88.41%) and non-fermenting bacteria 73 (11.59%). In the Enterobacterales group included Escherichia coli 371 (66.61%) of which 108 (29,1%) ESBL strains. The next etiologically significant uropathogens were Klebsiella- 99 (17, 77%), Enterobacter-36 (6,46%) and Proteus-32 (8,09). K.pneumoniae prevailed in comparison with other Klebsiella spp. ESBL producing was 34 (57, 6%) out of 59 K.pneumoniae isolates. Gram-negative non-fermenting rod were represented by Acinetobacter spp-34 (46.57%) and Pseudomonas spp 31 (42.47%). Of 34 Acinetobacter spp. isolates 22 (64.7%) were identified as Acinetobacter lwoffii. Among the gram-positive pathogens of UTI, Staphylococcus spp prevailed - 411 (59.57%), followed by Enterococcus spp 197 (28.55%) and Streptococcus spp 81 (11.73%). Coagulase-negative staphylococci 381 (92,7%) isolates out of total 411 staphylococcal isolates. Staphylococcus epidermidis 245 (59,61%) and Staphylococcus haemolyticus 81 (21,17%) were the most frequent isolated coagulase-negative staphylococci. Of 411 staphylococcal isolates, 182 (44.28%) were MRS Conclusion: We found that UTIs among our study population were predominantly caused by ten opportunistic pathogens. The most common uropathogens with a frequency of 66.9% were E. coli- 30.53%, S. epidermidis -20.16%, and Enterococcus spp. -16.21%. Frequently isolated pathogens included Klebsiella, S. haemolyticus spp., and Streptococcus spp. which amounted to 21.98%. The distribution within the patient group was equable and ranged from 6,67% to 8,15%. Etiologically significant pathogens included Enterobacter spp., Proteus spp., Acinetobacter spp., Pseudomonas spp. These bacteria accounted for 11.11%. The distribution within the group was again equable and ranged within 2,55% to 2,96%.

Introduction: Urinary tract infections (UTIs) remain one of the most important problems of modern urology and medicine. Infections bring great discomfort and significantly reduce the quality of life. UTIs rank second after respiratory tract infections in outpatients. The most common pathogen of UTI are E.coli. The study of the etiology of UTI has great clinical and epidemiological importance in routine practice.Objective: To assess the etiological significance of pathogens in the occurrence of urinary tract infections in the Karaganda region of Kazakhstan.Methods: A total of 2378 patients presenting UTIs were enrolled and each provided a urine sample. The study was carried out in the Clinical Microbiology Laboratory MediTEC-NS between 2 January and 29 December 2018. Identification of isolated microorganisms was carried out on a WalkAway 96 Plus microbiological analyzer, Microscan model manufactured by Beckman Coulter (USA). Statistical Analysis was performed using the STATISTICA-6 package.Results: Out of 2378 patients a total of 1177 (49,5%) urine samples tested positive by culture test. From these samples, 1356 strains of microorganisms were isolated, of which 84.79% were monoculture and 21% were of a mixed culture. Gram-positive bacteria 690 (50, 88%), Gram-negative bacteria 630 (46, 46%), and Candida 36 (2.65%) were identified. Gram-negative rods were represented by Enterobacterales 557 (88.41%) and non-fermenting bacteria 73 (11.59%). In the Enterobacterales group included Escherichia coli 371 (66.61%) of which 108 (29,1%) ESBL strains. The next etiologically significant uropathogens were Klebsiella- 99 (17, 77%), Enterobacter-36 (6,46%) and Proteus-32 (8,09). K.pneumoniae prevailed in comparison with other Klebsiella spp. ESBL producing was 34 (57, 6%) out of 59 K.pneumoniae isolates. Gram-negative non-fermenting rod were represented by Acinetobacter spp-34 (46.57%) and Pseudomonas spp 31 (42.47%). Of 34 Acinetobacter spp. isolates 22 (64.7%) were identified as Acinetobacter lwoffii. Among the gram-positive pathogens of UTI, Staphylococcus spp prevailed - 411 (59.57%), followed by Enterococcus spp 197 (28.55%) and Streptococcus spp 81 (11.73%). Coagulase-negative staphylococci 381 (92,7%) isolates out of total 411 staphylococcal isolates. Staphylococcus epidermidis 245 (59,61%) and Staphylococcus haemolyticus 81 (21,17%) were the most frequent isolated coagulase-negative staphylococci. Of 411 staphylococcal isolates, 182 (44.28%) were MRSConclusion: We found that UTIs among our study population were predominantly caused by ten opportunistic pathogens. The most common uropathogens with a frequency of 66.9% were E. coli- 30.53%, S. epidermidis -20.16%, and Enterococcus spp. -16.21%. Frequently isolated pathogens included Klebsiella, S. haemolyticus spp., and Streptococcus spp. which amounted to 21.98%. The distribution within the patient group was equable and ranged from 6,67% to 8,15%. Etiologically significant pathogens included Enterobacter spp., Proteus spp., Acinetobacter spp., Pseudomonas spp. These bacteria accounted for 11.11%. The distribution within the group was again equable and ranged within 2,55% to 2,96%.

Abstract Introduction: Urinary tract infections (UTIs) remain one of the most important problems of modern urology and medicine. Infections bring great discomfort and significantly reduce the quality of life. UTIs rank second after respiratory tract infections in outpatients. The most common pathogen of UTI are E.coli. The study of the etiology of UTI has great clinical and epidemiological importance in routine practice. Objective: To assess the etiological significance of pathogens in the occurrence of urinary tract infections in the Karaganda region of Kazakhstan. Methods: A total of 2378 patients presenting UTIs were enrolled and each provided a urine sample. The study was carried out in the Clinical Microbiology Laboratory MediTEC-NS between 2 January and 29 December 2018. Identification of isolated microorganisms was carried out on a WalkAway 96 Plus microbiological analyzer, Microscan model manufactured by Beckman Coulter (USA). Statistical Analysis was performed using the STATISTICA-6 package. Results: Out of 2378 patients a total of 1177 (49,5%) urine samples tested positive by culture test. From these samples, 1356 strains of microorganisms were isolated, of which 84.79% were monoculture and 21% were of a mixed culture. Gram-positive bacteria 690 (50, 88%), Gram-negative bacteria 630 (46, 46%), and Candida 36 (2.65%) were identified. Gram-negative rods were represented by Enterobacterales 557 (88.41%) and non-fermenting bacteria 73 (11.59%). In the Enterobacterales group included Escherichia coli 371 (66.61%) of which 108 (29,1%) ESBL strains. The next etiologically significant uropathogens were Klebsiella- 99 (17, 77%), Enterobacter-36 (6,46%) and Proteus-32 (8,09). K.pneumoniae prevailed in comparison with other Klebsiella spp. ESBL producing was 34 (57, 6%) out of 59 K.pneumoniae isolates. Gram-negative non-fermenting rod were represented by Acinetobacter spp-34 (46.57%) and Pseudomonas spp 31 (42.47%). Of 34 Acinetobacter spp. isolates 22 (64.7%) were identified as Acinetobacter lwoffii. Among the gram-positive pathogens of UTI, Staphylococcus spp prevailed - 411 (59.57%), followed by Enterococcus spp 197 (28.55%) and Streptococcus spp 81 (11.73%). Coagulase-negative staphylococci 381 (92,7%) isolates out of total 411 staphylococcal isolates. Staphylococcus epidermidis 245 (59,61%) and Staphylococcus haemolyticus 81 (21,17%) were the most frequent isolated coagulase-negative staphylococci. Of 411 staphylococcal isolates, 182 (44.28%) were MRS Conclusion: We found that UTIs among our study population were predominantly caused by ten opportunistic pathogens. The most common uropathogens with a frequency of 66.9% were E. coli- 30.53%, S. epidermidis -20.16%, and Enterococcus spp. -16.21%. Frequently isolated pathogens included Klebsiella, S. haemolyticus spp., and Streptococcus spp. which amounted to 21.98%. The distribution within the patient group was equable and ranged from 6,67% to 8,15%. Etiologically significant pathogens included Enterobacter spp., Proteus spp., Acinetobacter spp., Pseudomonas spp. These bacteria accounted for 11.11%. The distribution within the group was again equable and ranged within 2,55% to 2,96%.

Urinary tract infections are a major cause of morbidity and mortality in Mozambique. They are sometimes treated empirically with nitrofurantoin. However, little is known about this antibiotic’s performance and bacterial resistance in the country. This study analyzed the results of nitrofurantoin sensitivity tests requested in the Central Hospital of Maputo during 2012 and 2013. As result, 181 samples were tested and most cases (66.9%) showed absolute sensitivity but there were considerable cases of resistance (29.8%). Morganella morganii was the only bacteria presenting no absolute or intermediate resistance. The sensitivity was also high in the case of Escherichia coli (90%) and Gram-negative bacteria (66.7%). Serratia marcescens was mostly resistant (64.3%). The remaining bacteria showed inconclusive results. Thus they shall be subjected to a sensitivity test before prescription. Factors such as seasonality, patients’ sex and urine transparency did not seem to be reliable indicators of microbial resistance in the urine. Yet, a longer time span (over 5 years) might be sufficient for the sensitivity profile to change.

We present a case of a 47-year-old male who died unexpectedly from acute pulmonary hemorrhage 555 days after completing the BNT162b2 (Pfizer) COVID-19 vaccination primary series. Before death, he exhibited symptoms of a mild respiratory infection. Despite a healthy medical history and no medication use, the patient’s condition rapidly deteriorated and he experienced severe respiratory distress, followed by cardiopulmonary arrest with evidence of profuse pulmonary bleeding. Autopsy findings revealed massive lung congestion without embolism, normal heart size, moderate coronary atherosclerosis without myocardial infarction, and no evidence of other hemorrhagic events. The patient tested negative for COVID-19 and other respiratory pathogens at autopsy. Despite these findings, the medical examiner determined the cause of death was attributed to atherosclerotic and hypertensive cardiovascular disease, without considering the recent pulmonary hemorrhage and unremarkable medical history. Investigation into the vaccine batch indicated a higher-than-average number of serious adverse events, including fatalities. The patient's BNT162b2 batch was among the top 2.8% for reported deaths. Moreover, the autopsy failed to investigate potential contributions from the vaccine, such as the presence of the Spike protein or related antibodies. The evidence suggests that the pulmonary hemorrhage, exacerbated by a viral infection, was the immediate cause of death, with the COVID-19 vaccine potentially playing a role in the development of cardiopulmonary pathology and hemorrhage. We propose autopsy protocols for COVID-19 vaccine recipients to better investigate vaccine-related pathologies among those with one or more prior injections.

Managing severe bleeding, particularly in soft tissues and visceral injuries, remains a significant challenge in trauma and surgical care. Traditional hemostatic methods often fall short in wet and dynamic environments. This study addresses the critical issue of severe bleeding in soft tissues, proposing an innovative solution using a Polyethylene Glycol (PEG)-based hydrogel combined with zinc oxide (ZnO). The developed hydrogel forms a dual-network structure through amide bonds and metal ion chelation, resulting in enhanced mechanical properties and adhesion strength. The hydrogel, exhibiting excellent biocompatibility, is designed to release zinc ions, promoting coagulation and accelerating hemostasis. Comprehensive characterization, including gelation time, rheological properties, microstructure analysis, and swelling behavior, demon-strates the superior performance of the PEG/ZnO hydrogel compared to traditional PEG hydro-gels. Mechanical tests confirm increased compression strength and adhesive properties, crucial for withstanding tissue dynamics. In vitro assessments reveal excellent biocompatibility and en-hanced procoagulant ability attributed to ZnO. Moreover, in vivo experiments using rat liver and tail bleeding models demonstrate the remarkable hemostatic performance of the PEG/ZnO hy-drogel, showcasing its potential for acute bleeding treatment in both visceral and peripheral sce-narios.

Background: Bladder cancer (BC) development is highly related to immune cell infiltration and inflammation. This study aimed to construct a new classification of bladder cancer (BC) molecular subtypes based on immune cells-associated CpG sites. Methods: The genes of 28 types of immune cells were obtained from previous studies. Then methylation sites corresponding to immune cells-associated genes were acquired. Differentially methylation sites (DMSs) were identified between normal samples and bladder cancer samples. Unsupervised clustering analysis of differentially methylation sites was performed to divide into several subtypes. Then the potential mechanism of different subtypes was exploded. Result: Bladder cancer patients were divided into three groups. Cluster 3 (methylation-L) subtype had the best prognosis. Cluster 1 (methylation-M) had the worst prognosis. The distribution of immune cells, level expression of checkpoints, stromal score, immune score, ESTIMATEScore, tumor purity, APC_co_inhibition, APC_co_stimulation, HLA, MHC_class_I, Type_I_IFN_Reponse, and Type_II_IFN_Reponse were significant difference among three subgroups. The distribution of genomic alterations was different among them. Conclusion: The classification was accurate and stable. BC patients could be divided into three subtypes based on the immune cells-associated CpG sites. Specific biological signaling pathways, immune mechanisms, and genomic alterations were various among three subgroups. High level immune infiltration was a correlation with high level methylation. The lower RNAss score was associated with higher immune infiltration and higher level expression of CD274.

Metal exposure has been associated with a wide range of adverse birth outcomes and oxidative stress is a leading hypothesis of the mechanism of action of metal toxicity. We assessed the relationship between maternal exposure to essential and non-essential metals and metalloids in pregnancy and oxidative stress markers, and sought to identify windows of vulnerability and effect modification by fetal sex. In our analysis of 215 women from the PROTECT birth cohort study, we measured 14 essential and non-essential metals in urine samples at three time points during pregnancy. The oxidative stress marker 8-iso-prostaglandin F2α (8-iso-PGF2α) and its metabolite 2,3-dinor-5,6-dihydro-15-15-F2t-IsoP, as well as prostaglandin F2α (PGF2α), were also measured in the same urine samples. Using linear mixed models, we examined the main effects of metals on markers of oxidative stress as well as the visit-specific and fetal sex-specific effects. After adjustment for covariates, we found that a few urinary metal concentrations, most notably cesium (Cs) and copper (Cu), were associated with higher 8-iso-PGF2α with effect estimates ranging from 7.3 to 14.9 % for each interquartile range, increase in the metal concentration. The effect estimates were generally in the same direction at the three visits and a few were significant only among women carrying a male fetus. Our data show that higher urinary metal concentrations were associated with elevated biomarkers of oxidative stress. Our results also indicate a potential vulnerability of women carrying a male fetus.

To assess if SARS-CoV-2 infection induces changes in the urinary volatilomic fingerprint able to be used in the non-invasive COVID-19 diagnosis and management, urine samples of SARS-CoV-2 infected patients (62), recovered COVID-19 patients (30), and non-infected individuals (41) were analysed using solid-phase microextraction technique in headspace mode, combined with gas chromatography hyphenated with mass spectrometry (HS-SPME/GC-MS). In total, 101 volatile organic metabolites (VOMs) from 13 chemical families were identified, being terpenes, phenolic compounds, norisoprenoids, and ketones the most represented groups. Overall, a decrease in the levels of terpenes and phenolic compounds was observed in the control group, whereas norisoprenoids and ketones showed a significant increase. In turn, a remarkable increase was noticed in norisoprenoids and ketones and a milder increase in alcohols, furanic, and sulfur compounds in the recovery group than in the COVID-19 group. Multivariate statistical analysis identified sets of VOMs with the potential to constitute volatile signatures for COVID-19 development and progression. These signatures are composed of D-carvone, 3-methoxy-5-(trifluoromethyl)aniline (MTA), 1,1,6-trimethyl-dihydronaphthalene (TDN), 2-heptanone, and 2,5,5,8a-tetramethyl-1,2,3,5,6,7,8,8-octahydro-1-naphthalenyl ester acetate (TONEA) for COVID-19 infection and nonanoic acid, α-terpinene, β-damascenone, α-isophorone, and trans-furan linalool for patients recovering from the disease. This study provides evidence that changes in the urinary volatilomic profile triggered by SARS-CoV-2 infection constitute a promising and valuable screening and/or diagnostic and management tool for COVID-19 in clinical environment.

Glycosaminoglycans (GAGs) with unique structures from marine animals show intriguing pharmacological activities and negligible biological risks, providing more options for us to explore safer agents. Swim bladder is a tonic food and folk medicine, and its GAGs show good anticoag-ulant activity. In this study, two GAGs SJG-1.0 and GMG-1.0 have been extracted and isolated from the swim bladder of Sphyraena jello and Gadus morhua. The physicochemical properties, pre-cise structural characteristics, and anticoagulant activities of these GAGs were determined. The analysis results of the SJG-1.0 and GMG-1.0 showed that they were chondroitin sulfate (CS)/dermatan sulfate (DS) hybrid chains with molecular weights of 109.32 kDa and 123.13 kDa, respectively. They were mainly composed of the repeating disaccharide unit of -{IdoA-α1,3-GalNAc4S-β1,4-}- (DS-A). The DS-B disaccharide unit of -{IdoA2S-α1,3-GalNAc4S-β1,4-}- also existed in both SJG-1.0 and GMG-1.0. SJG-1.0 had a higher proportion of CS-O disaccharide unit -{-GlcA-β1,3-GalNAc-β1,4-}-, while GMG-1.0 contained higher proportion of CS-E disaccha-ride unit -{-GlcA-β1,3-GalNAc4S6S-β1,4-}-. The disaccharide compositions of the GAGs varied in a species-specific manner. Anticoagulant activity assay revealed that both SJG-1.0 and GMG-1.0 had potent anticoagulant activity, which can significantly prolong activated partial thrombosis time. GMG-1.0 also can prolong the thrombin time. SJG-1.0 showed no intrinsic tenase inhibition ac-tivity, while GMG-1.0 can obviously inhibit intrinsic tenase with EC50 of 58 nM. Their significantly different anticoagulant activities may be due to their different disaccharide structural units and proportions. These findings suggested that the swim bladder CS/DS hybrid chains with well-defined structure may be safer anticoagulants with low bleeding risk.

This study entailed the design and analysis of a 400 m-class underwater glider operated by a bladder-type buoyancy engine. The underwater glider was designed for high-speed movement with a maximum velocity of 2 knots. The shape of the hull was designed to reduce water resistance using the Myring hull profile equation. The reliability was verified by performing simulations using resistance coefficients. The relationship between the control value of the ballast discharged from the buoyancy engine and the glider's speed according to the path angle was analyzed. Further, the relationship between the optimal glide angle and the design control value of the ballast was derived, and the optimal glider speed was estimated accordingly. Based on the analysis results, a bladder-type buoyancy engine was developed, and the maximum speed of the tested underwater glider was measured via sea trials.

Background. TRPA1-related drugs alter sensation, particularly in conditions of inflammation. To further characterize the role of these drugs in bladder sensation, the TRPA1 agonist cinnamaldehyde (CMA) and oral true cinnamon spice were examined in preclinical models of bladder pain. Methods. Female, adult rats with and without acute zymosan-induced cystitis, were anesthetized and visceromotor (VMR) and cystometric responses to urinary bladder distension (UBD) determined following either the intravesical administration of CMA/vehicle solutions or the oral administration of true cinnamon/vehicle. ELISA measures of bladder TRPA1 content were also determined. Results. Acute cystitis resulted in increases in bladder TRPA1 content and produced an increased vigor of the VMRs to UBD and a lowering of micturition volume thresholds for activation of a micturition response. Intravesical CMA produced a robust inhibition of VMRs to UBD in rats with cystitis, but not in those without. Micturition volume thresholds were lowered by CMA in rats without cystitis, but had no additional effect in rats with cystitis. Oral cinnamon also produced a robust inhibition of VMRs to UBD in rats with cystitis and a mild augmentation of VMRs to UBD in rats without cystitis. Conclusions. A potentially analgesic effect of the spice, true cinnamon, in the treatment of the pain of acute cystitis was suggested by these preclinical studies. Human studies are indicated.

Hematoma caused by rupture of a pseudoaneurysm in the middle meningeal artery (MMA) after trauma usually present with epidural hematoma. Intracerebral hemorrhage (ICH) is extremely rare. We reviewed ICH due to rupture of MMA pseudoaneurysm. We found that in cases of acute ICH, a pseudoaneurysm was attached to the outer surface of the dura mater and associated with dura tear. In patients with acute ICH, intraoperative rupture of pseudoaneurysm developed just after bone flap removal. In cases of delayed ICH, pseudoaneurysms adhered to the inner surface of the dura mater. In patients with delayed ICH, intraoperative rupture of pseudoaneurysm developed during dura opening and hematoma removal. In situations of dura tear after trauma, rupture of pseudoaneurysms might lead to ICH via a dura tear. Pseudoaneurysms that develop in the MMA after trauma may exert pressure on and result in the thinning of the dura mater. In this case, pseudoaneurysms will adhere to the inner surface of the dura mater after several days or weeks. ICH might develop through both acute and delayed mechanisms following development of pseudoaneurysms in the MMA. Clinicians should pay attention to the timing of such ruptures during operations for both acute and delayed ICH.

(Background) the aim was to determine related factors to recurrent vitreous hemorrhage (RVH) in a sample of proliferative diabetic retinopathy (PDR) patients. (Methods) A retrospective, review-based study. We studied 183 eyes from 121 type 2 diabetes patients with PDR. We recorded diabetes duration, history of hypertension, retinal photocoagulation status, the posterior vitreous status, the mean HbA1c, mean hemoglobin, the renal function, and the systemic complications related to diabetes. We also recorded the use of ranibizumab prior to vitrectomy and the following surgical variables: the application of segmentation and diathermy on fibrovascular proliferative tissue, the use of silicone oil, and the occurrence of surgical complications, to study which independent variables were significantly related to the presence of RVH. (Results) Duration of diabetes (P= 0.028), hemoglobin (P=0.02), status of the posterior vitreous (P=0.03), retinal photocoagulation (P=0.002) and use of segmentation surgery technique (P=0.003) have significant link to the presence of RVH. In addition, patients with diabetic polyneuropathy, myocardial infarction and ischemia in lower limbs had more vitreous hemorrhage events (p&lt;0.001). (Conclusions) Patients with PDR and with longer diabetes duration, anemia, attached posterior vitreous, deficient retinal photocoagulation, and previously cardiovascular events, were more prone to RVH.

Men are more likely to develop cancer than women. In fact, male predominance is one of the most consistent cancer epidemiology findings. Additionally, men have a poorer prognosis and an increased risk of secondary malignancies compared to women. These differences have been investigated in order to better understand cancer and to better treat both men and women. In this review, we discuss factors that may cause this gender difference, focusing on urothelial bladder cancer (UBC) pathogenesis. We consider physiological factors that may cause higher male cancer rates, including differences in X chromosome gene expression. We discuss how androgens may promote bladder cancer development directly by stimulating bladder urothelium and indirectly by suppressing immunity. We are particularly interested in natural killer (NK) cells because they are important, but often overlooked anti-cancer lymphocytes.

Background: Atherosclerosis is a progressive disease that results from a combination of endothelial dysfunction and inflammatory arterial wall disorder. Stenosis of the carotid artery caused by atherosclerotic plaques is responsible for approximately 10-20% of strokes and transient ischemic attacks, and the low-grade intraplaque inflammation interferes with lesion stability and progression. Methods: In this cohort study, initially, 119 patients were enrolled who underwent carotid endarterectomy. Of these, 67 cases with active perilesional inflammatory infiltrate were chosen for further immunohistochemical examination. The CD68+ infiltrate, iNOS2+, Arg1, and CD31 expressions were quantified around the lipid core by digital morphometry. These results were correlated with the presence of morphological changes leading to plaque instability: ulceration, thrombosis, intraplaque hemorrhage, the presence of the lipid core, calcification, and neovascularization. Results: Patients with a stronger macrophage CD68+ infiltrate were associated with intraplaque hemorrhage (p=0.003). In 12 cases with dominant iNOS2 positivity, the occurrence of atherothrombosis was significantly more frequent (p=0.046). Plaque neovascularization, characterized by CD31+, was correlated with atherothrombosis (p=0.02). Conclusion: The intensity of macrophage infiltration correlates with intraplaque hemorrhage, and the presence of pro-inflammatory iNOS2+ macrophages is associated with atherothrombosis in endarterectomized carotid plaques. Neovascularization also has potential thrombotic capacity.

Aim: Exposure to polycyclic aromatic hydrocarbons (PAHs) has been in the past associated with adverse effects on human health among which belong also respiratory diseases. Our study is focused on the evaluation of PAH exposure by measuring the concentrations of their monohydroxylated metabolites (OH-PAHs) in urine and comparing their concentrations with the incidence of respiratory diseases in 2-year-old children from two locations of the Czech Republic – a control locality Ceske Budejovice and a previously highly contaminated mining district Most. Methods: The total number of 248 participants were sampled for urine samples that were analysed for the presence of 11 OH-PAHs using liquid-liquid extraction with ethyl acetate and clean-up employing dispersive solid phase extraction with a sorbent Z-Sep. Separation, identification and quantification of the target compounds was achieved by ultra-high performance liquid chromatography coupled to tandem mass spectrometry. The incidence of respiratory diseases was evaluated according to the questionnaires provided by the paediatricians. Results and discussion: The concentrations of measured OH-PAHs were higher in the urine samples collected from 2-year-old children living in Most compared to 2-year-old children from Ceske Budejovice. The same trend was observed also when the urine samples were analysed when these children were studied as newborns in our previous study. From all of the monitored respiratory diseases, only influenza due to unidentified influenza virus showed a difference between tested locations where the 2-year-old children living in Most were more frequently diagnosed with this disease. Conclusion: Even though the air pollution and lifestyle in both cities is very similar, we have observed higher incidence of respiratory diseases as well as higher concentration of OH-PAHs in urine of the 2-year-old children from Most. Therefore, we hypothesize that the population living in this previously highly contaminated location (in 1970s and 1980s) can carry some long-term health burden.

Background: Increase of collagen I (COL I)/COL III ratio enhances vessel wall stiffness and renders vessels less resistant to blood flow and pressure changes. We hypothesized that COL I/COL III ratio is increased in the brain arteriovenous malformations (bAVMs), which is associated with bAVM hemorrhage. Method: Surgically resected human bAVM samples and mouse bAVMs induced in three transgenic mouse lines with activin receptor-like kinase 1 or endoglin deletion in the endothelial cells or in the brain focally. Colony-stimulating factor receptor inhibitor was used to transiently deplete microglia. COL I and COL III levels, hemorrhage, and gene expression in bAVMs were analyzed. Results: The COL I and COL III levels and the COL I/COL III ratio were higher on human and mouse bAVMs than controls, which was associated with bAVM hemorrhage. Col I and Col III mRNAs were also increased in mouse bAVMs. The degree of microhemorrhage in mouse bAVMs was positively correlated with Col I/Col III ratios. Transient depletion of microglia reduced Col I/Col III ratio and microhemorrhage in mouse bAVMs. Conclusion: COL I/COL III ratio are increased in bAVM vessels, which is associated with bAVM hemorrhage. Depletion of microglia reduces Col I/Col III ratio and hemorrhage in mice bAVMs.

The underlying mechanisms of secondary neuronal damage following intracerebellar hemorrhage are not yet clear. We aimed to study the possible mechanisms in the mediation of secondary neuronal damage following intracerebellar hemorrhage. ICbH was induced by collagenase type VII-S into mice in 2 phases (n=24/phase): 12 in control group, 12 in day 1 group, 12 in day 3 group and another 12 in day 7 group. All mice underwent locomotor assessment and subsequently sacrificed on day 1, day 3 and day 7 respectively. Cerebellum from phase one and phase two were taken to study morphological, immunohistochemistry and oxidative stress respectively. Mice behavior disturbed following ICbH at day 3 and y 7 as compared with control. Besides, NO increased-on day 1 post induction and suppressed on day 3 and 7. Expressions of SOD, CAT, nNOS, GPX1 and COX-2 were significantly raised on day 3. Morphological studies of the perihaematoma region and tissue showed neuronal damage occurred from day 1 onwards, peaked on day 3 and continued day 7. NO and expression of genes be correlating with morphological changes. Briefly, NO and oxidative stress has an important role in the cascade of secondary neuronal damage of the perihematomal region of ICbH.

Postpartum hemorrhage is a complication during the puerperium that requires serious management, because it risks on threatening the mother's death. Currently, postpartum hemorrhage is still the main cause of maternal morbidity and mortality in the world. There is a need for a fast, precise and comprehensive handling effort involving all elements, such as the entire health team including doctors-nurses and families. The form of nursing intervention in postpartum hemorrhage patients can be in the form of nursing treatment or collaboration. The purpose of this review literature is to identify nursing treatment and nursing collaboration in postpartum hemorrhage patients as an effort to prevent maternal death. The writing method uses literature reviews by summarizing 10 articles publicated in 2019, 2020 and 2021 in 4 search data bases including Sciencedirect, Scopus, Proquest and Thompson. The review guidelines used are based on Prisma and the Joanna Briggs Institutute. The level of eligibility is identified through the title, abstract, research methodology and full text. The results of the reviews found are presented in a narrative form. The results of the review study found that there were 10 articles on postpartum hemorrhage management measures both in the effort of snoring treatment and collaboration including: optimizing the competence of service providers based on E_Learning , foot reflexology since the 4th stage of labor, 800 mcg sublingual Misoprostol, the use of the Digital Postpartum Hemorrhage Management Device ( DPHMD), bilateral-contralateral cervical clamps, suction tube uterine tampons, bilateral hypogastric artery (BHAL), evaluation of Shock Index, Carbetocin drugs and administration of Tranexamic acid 1 gram IV within 10 minutes of vaginal delivery. The conclusion of this review literature is that nursing treatment and nursing collaboration are proven to have a positive impact as an effort to prevent death in postpartum hemorrhage patients.

Introduction: Multiple sclerosis (MS) is a demyelinating, chronic, inflammatory and autoimmune disease of the central nervous system (CNS) with axonal degeneration, presenting a progressive and variable course. MS patients usually have complications, such as bladder dysfunction, presence of urinary symptoms and Urinary Tract infection (UTI), which is one of the three most common non-neurological complications in MS patients. Objective: Analyze the most diverse aspects of UTI in MS patients, focusing on risk factors, prevalence, hospitalization and mortality rates of UTIs in this group. Methods: A non-systematic review of articles published on PubMed in the last 10 years with the search terms "Urinary Tract Infection" AND "Multiple Sclerosis". Discussion: MS patients have a high UTI prevalence, mainly due to the occurrence of urinary disorders in these patients. The most common symptoms of UTI in MS patients are urinary urgency, polyuria, nocturia, urinary retention, and incontinence. Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae were the most found organisms and treatment is based on antibiotic therapy. Moreover, UTIs can precipitate outbreaks, worsen the disease, causing more damage and a severe neurological condition deterioration. Therefore, UTIs in this group are associated with a high hospitalizations rate and a high mortality rate. Conclusion: UTI represents a great risk and concern in MS patients. The high prevalence, hospitalization rate and mortality rate of UTI in MS is worrying, such as the cause-consequence relationship between UTIs and the use of corticosteroids in outbreaks. Therefore, it is important to be aware of a UTI in this group to make early diagnoses, adequate management, and new infections prevention. Thus, further studies are needed to thoroughly analyze each nuance of this important comorbidity for MS patients.

Introduction: We investigated the potential effect of smoking on pathological staging in clinically low-risk patients. Material-Methods: Data of 59 patients who were diagnosed with a bladder tumor for the first time and had a single lesion radiologically and endoscopically smaller than 3 cm were investigated, retrospectively. A total of 33 patients who currently smoke or smoked were classified as ever smokers group and 26 patients who did not ever smoke were classified as never smokers group. Pathological diagnoses of the patients in both groups were compared. Results: A total of 9 patients (27.3%) in ever smokers group and 18 patients (69.2%) in never smokers group had Ta disease (p<0.05). Morover, 19 patients (57.6%) in ever smokers group and 5 patients (19.2%) in never smokers group had T1 disease (p<0.05). The number of patients with low grade (LG) tumor were 8 (24.2%) and 19 (73.1%) in ever smoking and never smoking groups, respectively (p<0.05). The number of patients with high grade (HG) tumor were 25 (75.8%) and 7 (26.9%) in ever smoking and never smoking groups, respectively (p<0.05). Ta HG was detected in 9 (27.3%) patients in ever smoking group. In contrast, no patients in never smoking group had Ta HG disease (p<0.05). The number of patients with T1 HG was 17 (51.5%) in ever smoking group and 2 (7.69%) in never smoking group (p<0.05). Conclusion:Smoking seems to associate with pathologically worse stage and grade in patients with primary, single, < 3cm bladder cancer.

OBJECTIVE A quality improvement study to assess catheter-associated urinary tract infection (CAUTI) rate post-implementation of a bladder catheter with integrated active drain line urine clearance and automated intra-abdominal pressure monitoring in a burn intensive care unit (ICU). DESIGN Eight-year retrospective before and after study (2015–2022). SETTING A single American Burn Association verified Burn Center with fourteen inpatient beds. PATIENTS Patients meeting criteria for admission to a Burn Center METHODS Retrospective cohort study following the implementation of a novel urine output monitoring system with integrated drain line and urine clearance. Data from a 48-month (from January 2015-December 2018) historical control (period 1) were compared to data from a 28-month (from January 2020 to April 2022) post-implementation period (period 2). Pre- and post-implementation CAUTI event incidences were compared. Charts were reviewed to characterize the patients. RESULTS A total of 42 CAUTIs in 2243 patients were identified using the National Health and Safety Network (NHSN) definition during the analyzed period. There were 40 CAUTI events in period 1 and two CAUTIs in period 2. The incidence of CAUTI events pre-implementation was 0.030 (mean of 10 CAUTI events per year) compared to 0.002 (mean of 1 CAUTI event per year) post-implementation of an automatic drain line clearing UO monitoring system showing a significant reduction in CAUTI events (P<0.01, risk ratio novel vs. gravity bladder catheter 0.071, 95% confidence interval: 0.017-0.294). CONCLUSIONS CAUTIs were reduced in the period following the implementation of a novel urinary catheter system with an integrated active drain line and urine clearance in burn patients.

The purpose of this review is to present the current knowledge about the diagnostic and treatment options in bladder cancer (BCa) patients with clinically positive lymph nodes (cN+). In this review compaction of CT and MRI performance in preoperative prediction of lymph node invasion (LNI) in BCa patients was presented, along with other diagnostic methods. Most scientific societies do not distinguish cN+ patients in their guidelines, recommendations concern muscle-invasive bladder cancer (MIBC) and differ between associations. Currently, the standard treatment of patients with MIBC is radical cystectomy (RC) with bilateral pelvic lymph node dis-section (PLND). The template of PLND and its therapeutic value remain debatable. Moreover, most guidelines recommend neoadjuvant chemotherapy (NAC). However, there is still lack of definitive evidence of the superiority of neoadjuvant chemotherapy over adjuvant chemotherapy. Nevertheless, the curative treatment that provides the best long-term survival in cN+ patients is a multimodal approach with a combination of chemotherapy and RC. Recent studies demonstrate the growing importance of immunotherapy. Special attention should be paid to cN+ BCa patients as the oncological outcomes are significantly worse for this group.

Lower urinary tract dysfunction is clinically important because it may cause urinary tract infections, mainly due to accumulation of residual urine, and adversely affect renal function. In addition, it may cause urinary incontinence, strongly affecting the child’s quality of life. The function of the lower urinary tract is closely associated with function of the bowel because constipation is commonly present with bladder dysfunction. The interplay between the lower urinary tract and bowel function, coupled with common conditions such as detrusor overactivity and voiding dysfunction, requires a nuanced diagnostic approach. Detrusor overactivity, a benign but socially harmful condition, is the principal cause of daytime urinary incontinence in childhood. It needs to be differentiated from more serious conditions such as neurogenic bladder dysfunction or urethral obstruction. Voiding dysfunction, a habitual sphincter contraction during voiding, is common in children with detrusor overactivity, may be selflimiting but may also result in residual urine and urinary tract infections. It may resemble, in severe cases, the neurogenic bladder dysfunction, most often caused by spinal dysraphism which very often leads to recurrent urinary tract infections and high intravesical pressures, jeopardizing renal function. Voiding diary is crucial in the initial evaluation of lower urinary tract function in children.

(1) Background: Urinary tract infections (UTIs) are an important cause of perinatal and maternal morbidity and mortality. The aim of this study was to describe and compare the main pregnancy outcomes among pregnant patients with complicated and uncomplicated UTIs; (2) Methods: This retrospective study included 183 pregnant patients who were evaluated for uncomplicated UTIs and urosepsis in the Urology Department of ‘C.I. Parhon’ University Hospital, and who were followed up at a tertiary maternity hospital- ‘Cuza-voda’ from Romania between January 2014 and October 2023. The control group (183 patients) was randomly selected from the patient’s cohort who gave birth in the same time frame at the maternity hospital without urinary pathology. Clinical and paraclinical data was examined. Descriptive statistics and a conditional logistic regression model were used to analyze our data. (3) Results: Our results indicated that patients with urosepsis had increased risk of premature rupture of membranes (aOR: 5.59, 95%CI: 2.02- 15.40, p&lt; 0.001) and preterm birth (aOR: 2.47, 95%CI: 1.15- 5.33, p= 0.02). We could not demonstrate a statistically significant association between intrauterine growth restriction and preeclampsia with the studied urological pathologies. (4) Conclusions: Careful UTIs screening during pregnancy is needed for preventing maternal-fetal complications.

Ecdysterone is a phytosteroid widely discussed for its various pharmacological, growth-promoting and anabolic effects mediated by activation of estrogen receptor beta (ERbeta). Performance-enhancement in sports was demonstrated recently, and ecdysterone was consequently included in the Monitoring Program to detect potential patterns of misuse in sport. Only few studies on the pharmacokinetics of ecdysterone in humans have been reported so far. In this study, post-administration urines in twelve volunteers (single dose of 50 mg of ecdysterone) were analyzed using dilute-and-inject liquid chromatography-tandem mass spectrometry. Identification and quantitation of ecdysterone and of two metabolites, 14-deoxy ecdysterone and 14-deoxy poststerone was achieved. Ecdysterone was the most abundant analyte present in post-administration urines, detected for more than 2 days with a maximum concentration (Cmax) in the 2.8-8.5 h urines (Cmax = 4.4-30.0 µg/mL). The metabolites 14-deoxy ecdysterone and 14-deoxy poststerone were detected later reaching the maximum concentrations at 8.5-39.5 h (Cmax = 0.1-6.0 µg/mL) and 23.3-41.3 h (Cmax = 0.1-1.5 µg/mL), respectively. Cumulative urinary excretion yielded average values of 18%, 2.3% and 1.5% for ecdysterone, 14-deoxy ecdysterone and 14-deoxy poststerone, respectively. Ecdysterone and 14-deoxy ecdysterone were excreted following first order kinetics with half-lives calculated with three hours, while pharmacokinetics of 14-deoxy poststerone needs further evaluation.

Human papillomavirus (HPV) infections, primarily transmitted through sexual contact, have been linked to various cancers, including cervical, penile, anal, oropharynx, breast, and prostate cancers. This study presents a unique case of concurrent high-risk HPV35, HPV45, and HPV59 infections in both prostate and bladder cancer tissues from a single patient, representing the first documented instance worldwide with identical HPV types detected in two adjacent organs of the same individual. Employing a multiplex-PCR approach, gel electrophoresis, and Sanger sequencing, we confirmed the presence of these high-risk HPV types. Additionally, Western blot analysis using an HPV E7 antibody demonstrated the active expression of HPV oncoproteins in both cancer types. This discovery underscores the potential for HPV intra-organ transmission and necessitates further exploration of alternative transmission routes. The implications of our results offer new insights into the complex dynamics of HPV transmission in cancer pathogenesis.

Background: The study aimed to explore the association between the prognostic nutrition index (PNI) and in-hospital complication and mortality in patients with spontaneous intracerebral hemorrhage (ICH). Methods: We conducted a retrospective analysis using data from the Changhua Christian Hospital Clinical Research Database (CCHRD) between January 2015 and December 2022. 2402 patients were included, with the median PNI value set at 42.77. The restricted cubic spline model, Kaplan-Meier and ROC analysis for overall survival were used to evaluate the association of PNI with medical complications and mortality. Propensity score matching (PSM) analysis was performed to balance these clinical variables between groups, which could reduce potential bias to some extent. Results: PNI was significantly associated with in-hospital complications and 28-day and 90-day mortality in multivariate analysis. The main finding of our study is that a low PNI score at admission was independently associated with a poor ICH outcome. The Kaplan-Meier curves revealed higher survival rates in the high PNI group. PNI demonstrated sensitivity to predict medical complications and mortality based on ROC analysis. Conclusions Our study suggests that PNI could serve as a valuable marker for predicting medical complications and mortality in patients with spontaneous ICH.

Background: Micro-RNAs (miRNA) are emerging as biomarkers in the detection and prognosis of cancers due to their inherent stability and resilience. Methods: To summarize evidence regarding urinary miRNA (umiRNAs) role in the detection, prognosis and therapeutic management of urological cancers, we performed a systematic review of the most important scientific databases using the following keywords: (urinary mir-na)AND(prostate cancer); (urinary mirna)AND(bladder cancer); (urinary mirna)AND(renal cancer); (urinary mirna)AND(testicular cancer); (urinary mirna)AND(urothelial cancer). Results: Of all, 1364 articles were initially selected. Only original studies in the English language on human specimens were considered for inclusion in our systematic review. Thus, a convenient sample of 60 original articles was identified. Urinary miRNA (UmiRNAs) are downregulated in prostate cancers and may serve as potential non-invasive molecular biomarkers. Several umiR-NAs have been identified as diagnostic biomarkers of urothelial carcinoma and bladder cancer (BCa), allowing to discriminate malignant from non-malignant forms of haematuria. UmiRNAs could serve as therapeutic targets or recurrence markers of non-muscle invasive BCa and could predict the aggressivity and prognosis of muscle-invasive BCa. In renal cell carcinoma, miRNAs have been identified as predictors of tumour detection, aggressiveness, and progression to metastasis. Conclusion: umiRNAs could play an important role in the diagnosis, prognosis, and therapy of urological cancers.

Urethral prolapse (UP) is a rare condition in which the distal urethral mucosa protrudes circularly from the external urethral meatus. Urethral prolapse is seen in two age groups: prepubertal girls and postmenopausal women. The fact that it is seen in older women shows that it may be acquired. Causes of acquired UP include weakening of smooth muscle layers secondary to estrogen deficiency, chronic cough, chronic constipation, trauma, recurrent urinary tract infections, pelvic radiotherapy, and sexual abuse. The priority in treatment is conservative management, such as manual reduction, sitz baths, topical estrogen creams, and antibiotics. The general consensus is to switch to surgical treatment in patients who do not benefit from a conservative approach. In this case report, we describe the surgical treatment of a 56-year-old postmenopausal female patient with necrotic UP who presented with urinary retention.

Abstract Background: Alcohol consumption is linked to urinary sodium excretion and both of these traits are linked to hypertension and cardiovascular diseases (CVDs). The interplay between alcohol consumption and sodium on hypertension, and cardiovascular diseases (CVDs) is not well-described. Here, we used genetically predicted alcohol consumption and explored relationships between alcohol consumption, urinary sodium, hypertension, and CVDs. Methods: We performed a comparative analysis among 295,189 participants from the prospective cohort of the UK Biobank (baseline data collected between 2006 and 2010). We created a genetic risk score (GRS) using 105 published genetic variants in Europeans that were associated with alcohol consumption. We explored relationships between GRS, alcohol consumption, urinary sodium, blood pressure traits, and incident CVD. We used linear, logistic regression and Cox proportional hazards (PH) models in our analysis. Results: Our analyses supported an interaction effect between alcohol GRS and urinary sodium on hypertension (P interaction =0.03) and CVD (P interaction =0.03). In presence of high urinary sodium excretion, alcohol GRS increases blood pressure in a more enhanced fashion. Conclusions: Our results show that decrease in urinary sodium excretion offsets the risk posed by genetic risk of alcohol consumption.

Background and Objectives: Angioembolization has emerged as an effective therapeutic approach for pelvic hemorrhages; however, its exact effect size remains uncertain. Therefore, we conducted this systematic review and meta-analysis to investigate the effect size of embolization-related pelvic complications after nonselective angioembolization compared to that after selective angioembolization in patients with pelvic injury accompanying hemorrhage. Materials and Methods Relevant articles were collected by searching the PubMed, EMBASE, and Cochrane databases until June 24, 2023. Meta-analyses were conducted using odds ratios (ORs) for binary outcomes. Quality assessment was conducted using the risk of bias tool in non-randomized studies of interventions. Results: Five studies examining 357 patients were included in the meta-analysis. Embolization-related pelvic complications did not significantly differ between patients with nonselective and selective angioembolization (OR 1.581, 95% confidence interval [CI] 0.592 to 4.225, I2 = 0%). However, in-hospital mortality was more likely to be higher in the nonselective group (OR 2.232, 95% CI 1.014 to 4.913, I2 = 0%) than in the selective group. In the quality assessment, two studies were found to have a moderate risk of bias, whereas two studies exhibited a serious risk of bias. Conclusions: Despite the favorable outcomes observed with nonselective angioembolization concerning embolization-related pelvic complications, determining the exact effect sizes was limited owing to the significant risk of bias and heterogeneity. Nonetheless, the low incidence of ischemic pelvic complications appears to be a promising result.

Treatment of bladder cancer remains a critical unmet need and requires advanced approaches, particularly the development of local drug delivery systems. The physiology of the urinary bladder causes the main difficulties in the local treatment of bladder cancer: regular voiding prevents the maintenance of optimal concentration of the instilled drugs, while poor permeability of the urothelium limits the penetration of the drugs into the bladder wall. Therefore, much research effort is spent to overcome these hurdles, thereby improving the efficacy of available therapies. The explosive development of nanotechnology, polymer science and related fields has contributed to the emergence of a number of nanostructured vehicles (nano- and micro scale) applicable for intravesical drug delivery. Moreover, the engineering approach has facilitated the design of several macro-sized depot systems (centimeter scale) capable of remaining in the bladder for weeks and months. In this article, the main rationales and strategies for improved intravesical delivery are reviewed. Here, we focused on analysis of colloidal nano- and micro-sized drug carriers, and indwelling macro-scale devices which were evaluated for applicability in local therapy of bladder cancer in vivo.

Background: Biomarker development, improvement, and clinical implementation in the context of kidney disease has been a central focus of biomedical research for decades. To this point, only serum creatinine and urinary albumin excretion are well accepted biomarkers in kidney disease. With their known blind spot in early stages of kidney impairment and diagnostic limitations there is a need for better and more specific biomarkers. With the rise of large-scale analysis of thousands of peptides in serum or urine samples using mass spectrometry techniques hopes for biomarker development were high. Advances in proteomic research have led to the discovery of an increasing amount of potential proteomic biomarkers and identification of candidate biomarkers for clinical implementation in the context of kidney disease management. In this review we focus on urinary peptide and especially peptidomic biomarkers emerging from recent research and underline the role of those with the highest potential for clinical implementation. Methods: The Web of Science database (all databases) was searched on October 17th, 2020, using the search terms “marker*” OR biomarker* AND “renal disease” OR “kidney disease” AND “proteome*” OR “peptid*” AND “urin*”. English, full-text original articles on humans published within the last 5 years were included which were cited at least 5 times per year. Studies based on animal models, renal transplant studies, metabolite studies, studies on miRNA and studies on exosomal vesicles were excluded focusing on urinary peptide biomarkers. Results: The described search led to the identification of 3668 articles and application of inclusion and exclusion criteria as well as abstract and consecutive full-text analysis of 3 independent authors to a final number of 62 studies for this manuscript. The 62 manuscripts encompassed 8 established single peptide biomarkers and several proteomic classifiers including CKD273 and IgAN237. Discussion: This review provides a summary of recent evidence on single peptide urinary biomarkers in CKD while emphasizing the increasing role of proteomic biomarker research with new research on established and new proteomic biomarkers. Lessons learned from the last 5 years in this review might encourage future studies hopefully resulting in routine clinical applicability of new biomarkers.

Bacillus Calmette-Guérin (BCG) therapy for patients with non-muscle invasive bladder cancer (NMIBC) faces limitations in efficacy and significant side effects, aggravated by a recent global shortage. In this prospective clinical study, we report outcomes of sequential intravesical adminis-tration of gemcitabine and docetaxel (Gem/Doce) as the first-line treatment in BCG-naïve patients with high-risk NMIBC (HR NMIBC). From October 2019 until April 2022, we enrolled 52 patients and followed treatment protocol set by the University of Iowa. Follow-up assessments were con-ducted every 3 months. In this cohort, 25 (48.1%) patients were diagnosed with T1HG bladder cancer, 10 (19.2%) patients had carcinoma in situ (CIS), and 17 (32.7%) patients had a combination of CIS+T1HG. Median time to first recurrence in T1HG, CIS and T1HG+CIS groups was 11, 10.5 and 8.8 months, respectively. The recurrence-free survival was 98.1%, 94.2% and 80.8% at 6, 9 and 12 months, respectively. The rate of progression-free survival was 100%, 98.1% and 92.3% at 6, 9 and 12 months, respectively. We demonstrated the safety and efficacy of Gem/Doce therapy in BCG-naïve patients with HR NMIBC during a one-year follow-up. Further research with extended follow-up, as well as direct comparison of Gem/Doce and other anticancer agents, are essential.

This study introduces a compact Raman spectrometer with a 1064 nm excitation laser coupled with a fiber probe and an inexpensive motorized stage, offering a promising alternative to widely used Raman imaging instruments with 785 nm excitation lasers. The benefits of 1064 nm excitation for biomedical applications include further suppression of fluorescence background and deeper tissue penetration. The performance of the 1064 nm instrument in detecting cancer in human bladder resectates is demonstrated. Raman images with 1064 nm excitation were collected ex vivo from 10 human tumor and non-tumor bladder specimens and the results are compared to previously published Raman images with 785 nm excitation. K-Means cluster (KMC) analysis is used after pre-processing to identify Raman signatures of control, tumor, necrosis, and lipid-rich tissues. Hierarchical cluster analysis (HCA) groups the KMC centroids of all specimens as input. The tools for data processing and hyperspectral analysis were compiled in an open source Python library called SpectraMap (SpMap). In conclusion, the 1064 nm Raman system can differentiate between tumor and non-tumor bladder tissues in a similar way to 785 nm Raman spectroscopy. These findings hold promise for future clinical hyperspectral imaging.

Bladder cancer (BC) is the most common neoplasm of the urinary tract, which originates in the epithelium that covers the inner surface of the bladder. The molecular BC profile has led to the development of different classifications of non-muscle invasive bladder cancer (NMIBC) and muscle-invasive (MIBC). However, the genomic BC landscape profile of the Mexican population, including NMIBC and MIBC, is unknown. In this study, we aimed to identify somatic single nucleotide variants (SNVs) and copy number variations (CNVs) in Mexican patients with BC and their associations with clinical and pathological characteristics. We retrospectively evaluated 37 patients treated between 2012 and 2021 at the National Cancer Institute - Mexico (INCan). DNA samples were obtained from paraffin-embedded tumor tissues and ran exome sequencing. Strelka2 and Lancet packages were used to identify SNVs and insertions or deletions. FACETS was used to determine CNVs. We found a high frequency of mutations in TP53 and KMT2D, gains in 11q15.5 and 19p13.11-q12, and losses in 7q11.23. STAG2 mutations and 1q11.23 deletions were also associated with NMIBC and low histologic grade.

Urinary infections are defined as the presence of microorganisms in any part of the urinary system, with the exception of the distal urethra. The majority are uncomplicated infections, resolved on an outpatient basis, with empirical therapy. The objectives of this work were to study the sociodemographic characteristics of patients, analyze associated strains and examine the response of the main microorganisms to antibiotics. A retrospective observational study of all positive urine cultures between 2018 and 2022 was carried out in an Institution (8340 samples). Sociodemographic data were also collected. 61.3% were women, with an average age of 63.4 years, 43.2% from the Emergency Department. 13.5% were fitted, 56% of whom were women. 95.9% were not taking any antibiotics and among the individuals who were taking antibiotics, 50% were injected. Escherichia coli (53.5%) and Klebsiella pneumoniae (13,8%) are identified as the most prevalent strains. In the time periods analyzed, Escherichia coli decreased its resistance to 11 antibiotics and increased to 5 antibiotics, while Klebsiella pneumoniae decreased to 7 and increased to 7, with emphasis on the presence of 3 antibiotics with a resistance rate of 100 % to all Klebsiella pneumoniae strains identified in 2022.

Background Late-onset hypogonadism (LOH) is a condition caused by the decline of testosterone with aging, and is associated with various symptoms, including lower urinary tract symptoms (LUTS). Although some reports have shown that testosterone replacement treatment for LOH improved LUTS, no large study has revealed a correlation between LUTS and LOH. This study investigated the correlation between the severity of LOH and LUTS in Asian Japanese males of >40 years of age using a web-based questionnaire. Methods We asked a total of 2,000 Japanese male individuals to answer both the AMS and IPSS/QOL questionnaires using a web-based survey. Among these 2,000 individuals, 500 individuals were assigned to each of the following age groups: 40-49, 50-59, 60-69, and ≥70 years. LOH symptoms were assessed by AMS score as no/little (17-26 points), mild (27-36 points), moderate (37-49 points), and severe (≥50 points). To compare the risk of voiding and storage dysfunction according to the severity of AMS, voiding dysfunction was assessed by the sum of IPSS Q1, Q3, Q5, and Q6, while storage dysfunction was assessed by the sum of IPSS Q2, Q4, and Q7. Results The IPSS total score was positively correlated with the severity of AMS (shown as median [mean±SD]): no/little group, 2 (3.67±5.36); mild group, 6 (7.98±6.91); moderate group, 11 (12.49±8.63); and severe group, 16 (14.83±9.24) (p<0.0001). The prevalence of an IPSS total score of ≥8 in the AMS severity groups was as follows: no/little group, 13.3% (111 of 834); mild group, 38.3% (225 of 587); moderate group, 64.2% (244 of 380); severe group, 72.4% (144/199). The prevalence of nocturia in the AMS severity groups was as follows: no/little group, 19.8% (165 of 834); mild group, 31.5% (185 of 587); moderate group, 43.9% (167 of 380); and severe group, 50.8% (101 of 199). Conclusions Individuals with higher AMS values, which represents severe LOH symptoms, showed a higher risk of nocturia and LUTS.

Abstract Background: Small Cajal body-specific RNAs (scaRNAs) are a specific subset of small nucleolar RNAs (snoRNAs) that have recently been emerged as pivotal contributors in diverse physiological and pathological processes. However, their defined roles in carcinogenesis remain largely elusive. This study aims to explore the potential function and mechanism of SCARNA12 in bladder cancer (BLCA) and to provide a theoretical basis for further investigations into the biological functionalities of scaRNAs. Materials and Methods: TCGA, GEO and GTEx data sets were used to analyze the expression of SCARNA12 and its clinicopathological significance in BLCA. Quantitative real-time PCR (qPCR) and in situ hybridization were applied to validate the expression of SCARNA12 in both BLCA cell lines and tissues. RNA sequencing (RNA-seq) combined with bioinformatics analyses were conducted to reveal the changes of gene expression patterns and functional pathways in BLCA patients with different expression of SCARNA12 and T24 cell lines upon SCARNA12 knockdown. Single-cell mass cytometry (CyTOF) was then used to evaluate the tumor-related cell cluster affected by SCARNA12. Moreover, SCARNA12 was stably knocked down in T24 and UMUC3 cell lines by lentivirus-mediated CRISPR/Cas9 approach. The biological effects of SCARNA12 on the proliferation, clonogenic, migration, invasion, cell apoptosis, cell cycle and tumor growth were assessed by in vitro MTT, colony formation, wound healing, transwell, flow cytometry assays and in vivo nude mice xenograft models, respectively. Finally, chromatin isolation by RNA purification (ChIRP) experiment were further conducted to delineate the potential mechanisms of SCARNA12 in BLCA. Results: The expression of SCARNA12 was significantly up-regulated in both BLCA tissues and cell lines. RNA-seq data elucidated that SCARAN12 may play a potential role in cell adhesion and extracellular matrix (ECM) related signaling pathways. CyTOF results further showed that an ECM-related cell cluster with vimentin+, CD13+, CD44+, CD47+ was enriched in BLCA patients with high SCARNA12 expression. Additionally, SCARNA12 knockdown significantly inhibited the proliferation, colony formation, migration, and invasion abilities in T24 and UMUC3 cell lines. SCARNA12 knockdown prompted cell arrest in the G0/G1 and G2/M phase, and promoted the apoptosis in T24 and UMUC3 cell lines. Furthermore, SCARNA12 knockdown could suppress the in vivo tumor growth in nude mice. ChIRP experiment further suggested that SCARNA12 may combine transcription factors H2AFZ to modulate transcription program and then affect BLCA progression. Conclusion: Our study is the first to propose aberrant alteration of SCARNA12 and elucidate its potential oncogenic roles in BLCA via the modulation of ECM signaling. The interaction of SCARNA12 with the transcriptional factor H2AFZ emerges as a key contributor to the carcinogenesis and progression of BLCA. These findings suggest SCARNA12 may serve as a diagnostic biomarker and potential therapeutic target for the treatment of BLCA.

Chronic Kidney Disease (CKD) is a major public health concern with an increasing proportion of sufferers progressing to renal replacement therapy (RRT). Early identification of those at risk of disease progression could be key in improving outcomes. We hypothesise that urinary liver-type fatty acid binding protein (uL-FABP) may be a suitable biomarker for CKD progression and can add value to currently established biomarkers such as urinary protein to creatinine ratio (uPCR) 583 participants with CKD 1-5 (not receiving renal replacement therapy) entered a 2-yr prospective longitudinal study. UPCR and uL-FABP were measured at baseline and CKD progression was defined as either i) a decline in eGFR of >5ml/min/1.73m2 or an increase in serum creatinine by 10% at 1-yr or ii) a decline in eGFR of >6 ml/min/1.73m2, or an increase in serum creatinine by 20% at 2-yrs or iii) the initiation of RRT. A combined outcome of initiating RRT or death was also included. Approximately 40% of participants showed CKD progression. UL-FABP predicted CKD progression at both years 1 and 2 (OR 1.01, p<0.01). Sensitivity and specificity were comparable to those of uPCR (AUC 0.623 v 0.706) and heat map analysis suggested that uL-FABP in the absence of significant proteinuria can predict an increase in serum creatinine of 10% at 1yr and 20% at 2yr. The risk of the combined outcome of initiating RRT or death was 23% higher in those with high uL-FABP (p<0.01) independent of uPCR. UL-FABP appears to be a highly sensitive and specific biomarker of CKD progression. The use of this biomarker could enhance the risk stratification of CKD and its progression and should be assessed further.

This research used an experimental study design in which 60 subjects were randomly assigned to either an experimental (image e-book guidance) group or a control (text guidance) group after meeting the admission conditions and agreeing to participate in the study. It was proven that providing image e-book guidance before surgery significantly changed the behavior of patients and promoted relief of urinary catheter discomfort through self-efficacy to reduce urinary catheter pain after surgery. It was found that providing image e-book guidance can shorten the time for health education and provide patients with repeated medical education and familiarity with health guidance, which can help to address the important clinical service demand issue and the shortage of nursing staff.

Community pharmacists are involved in antimicrobial stewardship through self-care advice and delivering medications for uncomplicated infections. Objectives This mixed methods study aimed to identify opportunities to enhance the role of community pharmacists in the management of patients with suspected or confirmed urinary tract infection (UTI). Methods Data collection was through a service user survey (n=51) and pharmacist surveys and semi-structured interviews before (16 interviews, 22 questionnaires) and after (15 interviews, 16 questionnaires) trialling UTI leaflets designed to be shared with patients. Data were analysed inductively using thematic analysis and descriptive tabulation of quantitative data. Results Twenty-five percent (n=13/51) of service users with urinary symptoms sought help from a pharmacist first and 65% (n=33/51) were comfortable discussing their urinary symptoms with a pharmacist in a private space. Community pharmacists were confident as the first professional contact for service users with uncomplicated UTI (n=13/16, 81%), but indicated the lack of a specific patient referral pathway (n=16/16, 100%), the need for additional funding and staff (n=10/16, 62%), and the importance of developing prescription options for pharmacists (5/16, 31%). All community pharmacists reported playing a daily role in controlling antimicrobial resistance by educating service users about viral and bacterial infections and promoting a healthy lifestyle. Enhancing their role will need greater integrated working with general practices and more prescribers based in community pharmacy. Conclusion This study suggests that community pharmacists could play a greater role in the management of uncomplicated UTI. The current reconfiguration of primary care in England with primary care networks and integrated care systems could provide a real opportunity for this collaborative working with potential learning for international initiatives.

We use a system biology approach to translate the interaction of Bacillus Calmette-Gurin (BCG) + interleukin 2 (IL-2) for the treatment of bladder cancer into a mathematical model. The model is presented as a system of differential equations with the following variables: number of tumor cells, bacterial cells, immune cells, and cytokines involved in the tumor-immune response. This work investigates the delay effect induced by the proliferation of tumor antigen-specific effector cells after the immune system destroys BCG-infected urothelium cells following BCG and IL-2 immunotherapy in the treatment of bladder cancer. For the proposed model, three equilibrium states are found analytically. The stability of all equilibria is analyzed using the method of Lyapunov functionals construction and the method of linear matrix inequalities (LMIs).

Bladder cancer is one of the most common malignant diseases in the urinary system and a highly aggressive neoplasm. The prognosis is not favourable usually and its evolution for particular patients is very difficult to find out. In this paper we propose a dynamic mathematical model that describes the bladder tumor growth and the immune response evolution. This model is customized for a single patient, determining appropriate model parameter values via model calibration. Due to the uncertainty of the tumor evolution, using the calibrated model parameters, we predict the tumor size and the immune response evolution over the next few months assuming three different scenarios: favourable, neutral and unfavourable. In the former, the cancer disappears; in the second a 5mm tumor is expected around the middle of August 2018; in the worst scenario, a 5mm tumor is expected around the end of May 2018. The patient has been cited around June 15th, 2018, to check the tumor size, if it exists.

Little is known about the association between equol and bioavailable testosterone (BT) in adults. We examined the associations of urinary equol concentrations with serum total, bioavailable and free testosterone (FT), dehydroepiandrosterone sulfide (DHEAS), free androgen index (FAI) and sex hormone-binding globulin (SHBG) concentrations. This cross-sectional study included 1904 women aged 59.7 years. Urinary equol and serum sex hormone concentrations were measured. Overall, urinary equol tended to be inversely associated with bioactive forms of androgenic indices (BT, FT or FAI) but not with total testosterone (TT) or DHEAS. Urinary equol was also positively associated with SHBG. In multi-covariate-adjusted analyses stratified by menopausal status, graded and inverse associations between urinary equol and bioactive forms of androgenic indices (BT, FT and FAI) were observed in postmenopausal women (all p-trends <0.05), but not in premenopausal women. A significant positive association between urinary equol and SHBG was observed only in postmenopausal women. No significant associations were observed between urinary equol and TT or DHEAS in either group. A path analysis indicated that these associations of equol with androgens in postmenopausal women might be mediated by SHBG. Our findings indicated urinary equol exhibited graded and inverse associations with BT or FT but not TT in women.

Purpose: Carotid intraplaque hemorrhage (IPH) increases risk of territorial cerebral ischemic events, but different sequences or criteria have been used to diagnose or quantify carotid IPH. The purpose of this study was to compare manual segmentation and semi-automatic segmentation for quantification of carotid IPH on magnetization-prepared rapid acquisition with gradient-echo (MPRAGE) sequences. Methods: Forty patients with 16–79% carotid stenosis and IPH on MPRAGE sequences were reviewed by two trained radiologists with more than five years of specialized experience in carotid plaque characterization with carotid plaque MRI. Initially, the radiologists manually viewed the IPH based on the MPRAGE sequence. IPH volume was then measured by three different semi-automatic methods, with high signal intensity 150%, 175%, and 200%, respectively, above that of adjacent muscle on the MPRAGE sequence. Agreement on measurements between manual segmentation and semi-automatic segmentation was assessed using the intraclass correlation coefficient (ICC). Results: There was near-perfect agreement between manual segmentation and the 150% and 175% criteria for semi-automatic segmentation in quantification of IPH volume. The ICC of each semi-automatic segmentation were as follows: 150% criteria: 0.861, 175% criteria: 0.809, 200% criteria: 0.491. The ICC value of manual vs. 150% criteria and manual vs. 175% criteria were significantly better than the manual vs. 200% criteria (p < 0.001). Conclusions: The ICC of 150% and 175% criteria for semi-automatic segmentation are more reliable for quantification of IPH volume. Semi-automatic classification tools may be beneficial in large-scale multicenter studies by reducing image analysis time and avoiding bias between human reviewers.

Bladder cancer (BLCA) is the sixth most common type of cancer and has a dismal prognosis if diagnosed late. To identify treatment options for BLCA, we systematically evaluated data from the Broad Institute DepMap project. We found that urothelial BLCA cell lines are among the most sensitive to microtubule assembly inhibition by paclitaxel treatment. Strikingly, we unveiled that the top dependencies in BLCA cell lines include genes encoding proteins involved in microtubule assembly, thus highlighting the importance of microtubule network dynamics as a major vulnerability in human BLCA. In cancers, such as ovarian and breast, where paclitaxel is the golden standard of care, resistance to paclitaxel treatment has been linked to p53-inactivating mutations. To study the response of BLCA to microtubule assembly inhibition and its mechanistic link with the mutational status of p53 protein, we treated a collection of BLCA cell lines with a dose range of paclitaxel and performed a detailed characterization of the response. We herein discovered that BLCA cell lines are significantly sensitive to low concentrations of paclitaxel, independently of their p53 status. Paclitaxel induced a G2/M cell cycle arrest and growth inhibition, followed by robust activation of apoptosis. Most importantly, we revealed that paclitaxel triggered a robust DNA-damage response and apoptosis program without activating the p53 pathway. Integration of transcriptomics, epigenetic and dependency data demonstrated that the response of BLCA to paclitaxel is independent of p53 mutational signatures, but strongly depends on the expression of DNA-repair genes. Our work highlights urothelial BLCA as an exceptional candidate for paclitaxel treatment and paves the way for the rational use of a combination of paclitaxel and DNA-repair inhibitors as an effective, novel therapeutic strategy.

Indwelling urinary catheters are common in healthcare settings and can lead to catheter-associated urinary tract infection (CAUTI). Long-term catheterization causes polymicrobial colonization of the catheter and urine, for which the clinical significance is poorly understood. Through prospective assessment of catheter urine colonization, we identified Enterococcus faecalis and Proteus mirabilis as the most prevalent and persistent co-colonizers. Clinical isolates of both species successfully co-colonized in a murine model of CAUTI, and they were observed to co-localize on catheter biofilms during infection. We further demonstrate that P. mirabilis preferentially adheres to E. faecalis during biofilm formation, and that contact-dependent interactions between E. faecalis and P. mirabilis facilitate establishment of a robust biofilm architecture that enhances antimicrobial resistance for both species. E. faecalis may therefore act as a pioneer species on urinary catheters, establishing an ideal surface for persistent colonization by more traditional pathogens such as P. mirabilis.

Background: We aimed to investigate the effectiveness of postnatal ultrasonography in determining congenital anomalies of the kidney and urinary tract in term infants with or without a history of congenital anomalies of the kidney and urinary tract in the prenatal period. Methods: In this retrospective cohort study, the records of term infants aged between six weeks and three months undergoing urinary system ultrasonography during routine child care were examined. Results: Congenital anomalies of the kidney and urinary tract was determined in 121 (4.62%) of the 2620 cases included in the study. The most common anomaly was hydronephrosis (in 69.4% of the congenital anomalies of the kidney and urinary tract cases and 3.21% of all cases). Thirty-two of the 84 (38.1%) hydronephrosis cases detected by postnatal ultrasonography, three of the nine (33.3%) renal agenesis cases, four of the seven (57.1%) horseshoe kidneys cases, one of the four (25%) multicystic dysplastic kidney cases and two of the two (100%) duplex system cases could not be detected by prenatal ultrasonography. On the other hand, hydronephrosis was not detected at postnatal ultrasonography in 29 (1.1%) cases which detected mild or moderate hydronephrosis by prenatal ultrasonography scanning. Conclusions: In our study, it was observed that approximately one-third of the cases of hydronephrosis, unilateral renal agenesis, duplex system, horseshoe kidney, and ectopic kidney could not be detected at prenatal ultrasonography screening. We therefore believe that, in addition to prenatal ultrasonography screening, postnatal ultrasonography screening of all children for urinary tract anomalies would be beneficial.

Higher salt (sodium) intake has been associated with a higher blood pressure (BP). The association degree may be influenced by factors such as age, origin and dietary components. This study aimed to evaluate the 24-hours urinary sodium (Na) and potassium (K) excretion in normotensive and hypertensive Dominicans adults and estimate their salt intake. 163 volunteers (18-45, 46-80 years) participated in a cross-sectional study. 24-hours Na and K urinary excretion were measured using an ion selective electrode technique. Na and K urinary excretion (99.4±46.5 and 35.0±17.5 mmol/24h) did not correlated with BP, except in the normotensive group in which K correlated with SBP (0.249, p=0.019). Na and K excretion were similar for normo- and hypertensive subjects. Na-to-K molar ratio (3.1±1.3) was higher in younger subjects (p=0.040). Na-to-K ratio was associated with DBP in the total group (r=0.153, p=0.052), in the hypertensive group (r=0.395, p<0.001) and in the older group with SBP (0.350, p=0.002) and DBP (0.373, p<0.001). In the older group, Na-to-K ratio and DBP correlated after controlling for subjects with hypertension controlled by treatment (r=0.236, p=0.041). The Na-to-K ratio correlated, when salt intake was over 5g/d (52.2%), with SBP (rho=0.219, p=0.044) and DBP (rho=0.259, p=0.017). Determinants of BP were age-dependent and in younger subjects were: sex (SBP, beta: 14.02±2.87, p<0.001) and body mass index (BMI) (beta:-12.07±3.72, p=0.001, beta:9.44±2.87, p=0.001, for SBP and DBP, respectively) and, in the olders, the Na-to-K ratio, for SBP (beta:6.7±2.4, p=0.005) and DBP (beta:3.8±1.1, p<0.001). The mean Na and salt intakes (2.3 and 5.8 g/d) were slightly higher and K intake lower (1.4 g/d) than WHO recommendations.

Urinary tract infections in kidney transplant patients are a real challenge. We conducted a retrospective observational study, enrolling all kidney transplant patients hospitalized for urinary tract infection (UTI), with the objective to evaluate the epidemiology, clinical sta-tus, therapeutic management, and clinical outcome of kidney transplant patients hospi-talized for urinary tract infection in a university hospital. From our real-life experience, infection with multidrug-resistant germs was confirmed as a risk factor for the severe evolution of the infection and at the same time the re-evaluation of immunosuppressive therapy could be an important therapeutic strategy in the course of infection. Prompt ini-tiation of empiric antibiotic therapy upon initiation of microbiological investigations could potentially reduce the risk of severe infection progression.

Urinary extracellular vesicles (uEV) hold non-invasive RNA biomarkers for genitourinary tract diseases. However, missing knowledge about reference genes and effects of pre-analytical choices hinder biomarker studies. We aimed to assess how pre-analytical variables (urine storage temperature, isolation workflow) affect diabetic kidney disease (DKD) -linked miRNAs or kidney -linked miRNAs and mRNAs (kidney-RNAs) in uEV isolates and to discover stable reference mRNAs across diverse uEV datasets. We studied nine raw and normalized sequencing datasets including healthy controls and individuals with prostate cancer or type 1 diabetes with or without albuminuria. We focused on kidney-RNAs reviewing literature for DKD-linked miRNAs from kidney tissue, cell culture and uEV/urine experiments. RNAs were analyzed by expression heatmaps, hierarchical clustering and selecting stable mRNAs with normalized counts (>200) and minimal coefficient of variation. Kidney-RNAs were decreased after urine storage at -20°C vs -80°C. Isolation workflows captured kidney-RNAs with different efficiencies. Ultracentrifugation captured DKD -linked miRNAs that separated healthy and diabetic macroalbuminuria groups. Eleven mRNAs were stably expressed across the datasets. Hence, preanalytical choices had variable effects on kidney-RNAs – analyzing kidney-RNAs complemented global correlation, which could fade differences in some relevant RNAs. Replicating prior DKD-marker results and discovery of candidate reference mRNAs encourages further uEV biomarker studies.

Objective: The goal of the present study was to evaluate the treatment with Canephron® after the diagnosis of acute cystitis or urinary tract infection (UTI) with regards to the risk of a sporadic recurrent UTI, frequent recurrent UTIs, UTI associated sick leave, additional antibiotic prescriptions, and renal complications (pyelonephritis) compared to standard antibiotic treatment. Methods: This retrospective cohort study was based on data from the IMS® Disease Analyzer database (IQVIA), and included outpatients in Germany with at least one diagnosis of acute cystitis or UTI with a prescription of either Canephron® or standard antibiotics between January 2016 and June 2019 in general practitioner (GP), gynecologist, or urologist practices from which data were obtained. Multivariable regression models were used to investigate the association between Canephron® prescription and the amount of sporadic or frequent recurrent UTIs, as well as the duration of UTI associated sick leave, amount of additional antibiotic prescriptions, and cases of pyelonephritis. The effects of Canephron® were adjusted for age, sex, insurance status, and Charlson Comorbidity Score (CCI). Results: 2,320 Canephron® patients and 158,592 antibiotic patients were available for analysis. Compared to antibiotic prescription, Canephron® prescription was significantly associated with less sporadic recurrences of UTI infections 30-365 days after the index date (odds ratio [OR]: 0.66; 95% confidence interval [CI]: 0.58–0.72), as well as with less frequent recurrences of UTI infections (OR: 0.61; 95% CI: 0.49–0.88), and with minor additional antibiotic prescription within 31-365 days (OR: 0.57; 95% CI: 0.52-0.63). No significant differences were observed between the Canephron® and antibiotic cohorts with regard to the likelihood of sick leave (OR: 0.99; 95% CI: 0.86–1.14), new antibiotic prescription within 1-30 days (OR: 1.01; 95% CI: 0.87-1.16) and occurrences of pyelonephritis (Hazard Ratio (HR): 1.00; 95% CI: 0.67-1.48). Conclusion: These real world data show that Canephron® is an effective and safe symptomatic treatment for acute cystitis or UTI. It should be considered as an alternative treatment in particular also to strengthen antimicrobial stewardship strategies.

Objective: The aim of the study was to evaluate the influence of a suburethral sling implantation on the urge symptoms in patients suffering mixed urinary incontinence (MUI) with predominant stress component in case of. Material and methods: The study group was 220 woman with stress urinary incontinence (SUI), among them 35 women with stress-predominant MUI, treated primary with suburethral sling implantation. In 85.7% (N=30) TOT and in 14.3% (N=5) TVT was performed. The clinical symptoms and QOL were assesed before and after treatment using bladder diary and QOL questionnaire. Other additional treatment was also evaluated.Results: Subjective improvement of urge symptoms was observed in 97.1% of woman in the study group. ‘Wet OAB’ symptoms were reduced from 68.6% to 28.6% after sling procedure. Nocturia and pollakiuria were reduced from 45.7% to 11.4% and 8.6% respectively. Nocturia and pollakiuria de novo were observed in 2 (5.4%) and 1 (2.7%) patients respectively. After the sling procedure in 28.6 % (N=10) pharmacotherapy with solifenacin was administered for 2-4 months, in 8.6% (N=3) intravesical injection of botulinum toxin was performed due to persisting OAB symptoms.Conclusion: suburethral sling implantation in woman with stress- predominant MUI, although dedicated to treat SUI symptoms, seems to improve also the urge component of MUI.

Our previous study found that intravesical perfusion metformin has excellent inhibitory effects against bladder cancer (BC). However, this administration route allows the drug to be diluted and excreted in urine. Therefore, increasing the adhesion of metformin to the bladder mucosal layer may prolong the retention time and increase the pharmacological activity. It is well known that chitosan (Cs) has a strong adhesion to the bladder mucosal layer. Thus, this study established a novel for-mulation of metformin to enhance its antitumor activity by extending its retention time. In this research, we prepared Cs freeze-dried powder and investigated the effect of metformin-loaded chitosan hydrogels (MLCH) in vitro and in vivo. The results showed that MLCH had a strong in-hibitory effect against proliferation and colony formation in vitro. The reduction in BC weight and expression of tumour biomarkers in orthotopic mice showed the robust antitumor activity of MLCH via intravesical administration in vivo. The non-toxic profile of MLCH was observed as well, using histological examinations. Mechanistically, MLCH showed stronger functional activation of the AMPK/mTOR signalling pathway compared with metformin alone. These findings highlighted the potential of this novel formulation as an efficient candidate for managing BC via intravesical ad-ministration.

Carboxypeptidase A4 (CPA4) has shown the potential possibility as a biomarker in the early diagnosis for certain cancers. However, no previous research has linked CPA4 to therapeutic or prognostic significance in bladder cancer. Using data from The Cancer Genome Atlas (TCGA) database, we set out to determine the full extent of the link between CPA4 and BLCA. We further analyzed the interacting proteins of CPA4 and infiltrated immune cells via TIMER2，STRING and GEPIA2 databases. The expression of CPA4 in tumor and normal tissues was compared using the TCGA+GETx database. The connection between CPA44 expression and clinicopathologic characteristics and overall survival (OS) was investigated using multivariate methods and Kaplan-Meier survival curves. The potential functions and pathways were investigated via gene set enrichment analysis. Furthermore, we analyze the associations between CPA4 expression and infiltrated immune cells with their respective gene marker sets using the ssGSEA, TIMER2, and GEPIA2 databases. Compared to matching normal tissues, human CPA4 was found to be substantially expressed. We confirmed that overexpression of CPA4 is linked with shorter OS, DSF, PFI, and increased diagnostic potential using Kaplan-Meier and ROC analysis. The expression of CPA4 is related to T-bet, IL12RB2, CTLA4, and LAG3, among which T-bet and IL12RB2 are Th1 marker genes, while CTLA4 and LAG3 are related to T cell exhaustion, which may be used to guide the application of checkpoint blockade and the adoption of T cell transfer therapy.

The study aims to compare the efficacy and safety of bulking agents and single-incision slings in the treatment of urinary incontinence in 159 patients during a 29-month follow-up period. Of the 159 patients suffering from stress urinary incontinence, 64 were treated with bulking agents and 75 with a single incision sling. The ICIQ-UI-SF, PISQ-12, FSFI, FSDS, and PGI-I were used to assess efficiency and quality of life. In the 29-month follow-up, the bulking agents showed significantly increased efficacy and safety. Compared to the ones treated with a single-incision sling, the patients treated with bulking agents showed less and mild postoperative complications. Furthermore, at our follow-up there was no discernible difference in terms of effectiveness or quality of life between patients treated with bulking agents and those treated with single-incision slings

To examine the association of clinical, treatment, and dose parameters with late urinary toxicity after low-dose-rate brachytherapy (LDR-BT) for prostate cancer, we retrospectively studied patients with prostate cancer who underwent LDR-BT from January 2007 through December 2016. Urinary toxicity was assessed using the International Prostate Symptom Score (IPSS) and Overactive Bladder (OAB) Symptom Score (OABSS). Severe and moderate lower urinary tract symptoms (LUTS) were defined as IPSS ≥ 20 and ≥ 8, respectively; OAB was defined as a nocturnal frequency of ≥ 2 and a total OABSS of ≥ 3. In total, 203 patients (median age, 66 years) were included, with a mean follow-up of 8.4 years after treatment. The IPSS and OABSS worsened after 3 months of treatment; these scores improved to pretreatment levels after 18–36 months in most patients. Patients with a higher baseline IPSS and OABSS had a lower frequency of moderate and severe LUTS and OAB at 24 and 60 months, respectively. LUTS and OAB at 24 and 60 months were not correlated with the dosimetric factors of LDR-BT. Although the rate of long-term urinary toxicities assessed using IPSS and OABSS was low, the baseline scores were related to long-term function. Refining patient selection may further reduce long-term urinary toxicity.

(1) Background: Alcohol abuse has a high impact on the mortality and morbidity related to a great number of diseases and is responsible for the development of alcoholic liver disease (ALD). It remains challenging to detect and evaluate its severity, which is crucial for prognosis. In this work, we studied if urinary EVs (uEVs) could serve in diagnose and evaluate cirrhosis in ALD. (2) Methods: uEVs characterization by cryo-electron microscopy (Cryo-EM), Nanoparticle Tracking Analysis (NTA) and Western blotting (WB) was performed in a cohort of 21 controls and 21 cirrhotic patients. Then, proteomics of urinary EVs (uEVs) was carried out in a second cohort of 6 controls and 8 patients in order to identify new putative biomarkers for cirrhosis in ALD. (3) Results: uEVs concentration, size and composition were altered in cirrhotic patients. A total of 1304 proteins were identified in uEVs, and 90 of them were found to be altered in cirrhotic patients. (4) Conclusions: uEVs could be considered as a tool and a supplier of new biomarkers for ALD, whose application would be especially relevant in chronic patients. Yet, further research is necessary to obtain more relevant result in clinical terms.

Background: Early identification and prevention of hypoxic ischemic encephalopathy (HIE) may reduce neonatal mortality and morbidity. Objective: We aimed to correlate between urinary Activin-A and MRI (conventional and Diffusion-weighted) and the severity of HIE in full-term neonates. Methods: Forty-five full-term neonates with HIE admitted to NICU and 15 normal neonates were enrolled into the study. The concentration of urinary Activin-A was determined using enzyme immunoassay kits and MRI were done. Correlations between urinary Activin-A and MRI with the degree of HIE were done. Results: Urinary Activin-A levels were significantly higher in neonates with HIE than controls (P<0.001). It was positively correlated with the clinical grading of HIE and a cutoff value of 0.08µg/l on day-1 after birth had a sensitivity of 98.6% and specificity of 97.1% for prediction of HIE. DW-MRI detected HIE with a high sensitivity (85%) compared to the low sensitivity of conventional MRI (35%). An ADC value of ≤ 0.8 was the best sensitivity-specificity cutoff point for detecting severe ischemic injury. DW-MRI imaging was positively correlated with Urinary Activin-A and both of them were positively correlated with the clinical grades of HIE (P < 0.001). Conclusions: DW-MRI imaging is correlated well with urinary Activin-A in full-term neonates with HIE and both of them are correlated with the degree of HIE. Early determination of urinary Activin-A combined with DW-MRI imaging can early detect HIE and its severity in full-term neonates with HIE.

Uropathogenic E. coli (UPEC) is the main etiologic agent of urinary tract infections (UTI) and possesses virulence and resistance determinants commonly harbored in mobilizable genetic elements such as plasmids or pathogenicity islands (PAI). UPEC belongs to the group of Ex-traintestinal pathogenic E. coli, however the existence of hybrid strains has been described; these possess both diarrheagenic (DEC) and extraintestinal (ExPEC) E. coli traits and are considered as "hypervirulent strains," which represents a significant health problem. This study aimed to de-termine the prevalence of UPEC PAI, ExPEC sequence types (ST), DEC genes, carbapenemase and extended-spectrum β-lactamase (ESBL) phenotypes, fluoroquinolones/aminoglycosides resistance genotypes and the presence of plasmids in 40 clinical isolates previously characterized as UPEC. A 72.5% of the isolates presented PAI, mainly PAI IV536 (53%). Sixty-five percent of the β-lactam-resistant isolates were positive for ESBL phenotype, and 100% of the car-bapenem-resistant isolates were carbapenemase producers. The most prevalent ESBL-associated gene was blaCTX-M-2 (60%), while among isolates resistant to fluoroquinolones and aminoglycosides the most frequent resistance gene was aac(6')Ib (93%). Plasmid bands were present in 57% of the isolates. Seventy percent belonged to the ST131 clonal group. The presence of molecular markers associated with DEC pathotypes was detected in 20 isolates; 60% were classified as hybrid pathotypes. These data suggest, in addition to an important pathogenic potential, the existence of hybrid pathotypes in clinical isolates of E. coli causing UTI in the Mexican population.

It was the aim of this study to compare the ratio of salbutamol and its major metabolite salbutamol-4’-O-sulfate as well as the quantity excreted renally after oral and inhalative administration. Additionally, the excretion pattern after application of racemic salbutamol opposed to the pure enantiomer levosalbutamol was evaluated. For quantitation of the sulfonated metabolite of salbutamol, reference material was synthesized and characterized by NMR and HRMS. Urine samples were analyzed by ultrahigh performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Salbutamol is mainly metabolized by sulfotransferase 1A3 (SULT1A3), which is most abundantly found in the jejunum. A high first pass effect occurs upon oral administration, which leads to a higher amount of salbutamol-4’-O-sulfate in urine compared to unchanged salbutamol excreted within the first hour post administration. Thus, when administered orally, the proportion of metabolite to total salbutamol was higher than for inhalative administration in the early urinary excretion. Levosalbutamol is the favored enantiomer of SULT1A3 and therefore metabolized at a higher rate whereas racemic salbutamol shows a reduced proportion between metabolite and parent compound. The amount of sulfoconjugate was found higher than that of the parent compound for all urine samples except for those excreted in the first hour after inhalative administration.

Combined radiation with hemorrhage (combined injury, CI), exacerbates hematopoietic acute radiation syndrome and mortality compared to radiation alone (RI). We evaluated the effects of RI or CI on blood cell depletion as a biomarker to differentiate the two. Male CD2F1 mice were exposed to 8.75 Gy γ- radiation (60Co). Within 2 h of RI, animals were bled under anesthesia 0% (RI) or 20% (CI) of total blood volume. Blood samples were collected at 4-5 h and days 1, 2, 3, 7, and 15 after RI. CI decreased WBC at 4-5 h and continued to decrease them until day 3; counts then stayed at the nadir up to day 15. CI decreased neutrophils, lymphocytes, monocytes, eosinophils and basophils more than RI on day 1 or day 2. CI decreased RBCs, hemoglobin and hematocrit on days 7 and 15 compared to RI, whereas Hemorrhage alone returned to the baseline on days 7 and 15. RBCs depleted after CI faster than post RI. Hemorrhage alone increased platelet counts on days 2, 3, and 7, which returned to the baseline on day 15. Our data suggest that WBC depletion may be a biomarker within 2 days post-CI and RBC depletion after 3 days post-CI.

Lower urinary tract dysfunction, such as incontinence or urinary retention, is one of the leading consequences of neurological diseases. This significantly impacts the quality of life for those affected, with implications extending not only to humans but also to clinical veterinary care. Having motor and sensory fibers, the pudendal nerve is an optimal candidate for neuromodulation therapies using bidirectional intraneural prostheses, paving the way towards the restoration of a more physiological urination cycle: bladder state can be detected from recorded neural signals, then an electrical current can be injected to the nerve based on the bladder real-time need. To develop such prostheses and investigate this novel approach, animal studies are still required since the morphology of the target nerve is fundamental to optimize the prosthesis design. This study aims to describe the porcine pudendal nerve as a model for neuromodulation studies aiming at restoring lower urinary tract dysfunction. Five male farm pigs were involved in the study. First, a surgical procedure to access the porcine pudendal nerve without muscle resection was developed. Then, an intraneural interface was implanted to confirm the presence of fibers innervating the external urethral sphincter by measuring its electromyographic activity. Finally, the morpho-physiology of the porcine pudendal nerve at the level of surgical exposure was described by using histological and immunohistochemical characterization. This analysis confirmed the nerve fasciculate nature and the presence of mixed fibers with a spatial and functional organization. These achievements pave the way for further pudendal neuromodulation studies by using a clinically relevant animal model with the potential for translating the findings into clinical applications.

Total Parenteral Nutrition (TPN), which uses intravenous administration of nutrients, minerals and vitamins, is essential in sustaining premature infants until they transition to enteral feeds. There is limited information on metabolomic differences between infants on TPN and enteral feeds. We performed untargeted global metabolomics on urine samples collected between 23-30 days of life from 314 infants born &lt;29 weeks gestational age from the TOLSURF and PROP cohorts. Principal component analysis across all metabolites showed a separation of infants solely on TPN as compared to infants who had transitioned to enteral feeds, indicating global metabolomic differences between infants based on feeding status. Among 913 metabolites that passed quality control filters, 609 varied in abundance between infants on TPN vs enteral feeds at p&lt;0.05. Of these, 88% were in the direction of higher abundance in the urine of infants on enteral feeds. In a subset of infants with longitudinal analysis, both concurrent and delayed changes in metabolite levels were observed with initiation of enteral feeds. Infants on enteral feeds had higher concentrations of essential amino acids, lipids, and vitamins, which are necessary for growth and development, suggesting a nutritional benefit of an enteral feeding regimen.

Background: The nutritional status of women during pregnancy can have a considerable effect on maternal and fetal health, and on perinatal outcome. The aim was to assess the changes occurring in dietary iodine intake, KI supplementation, and smoking habit, and the impact of these changes on the urinary iodine concentration (UIC) during pregnancy in a population of women in Catalonia (Spain). Methods: Between 2009-2011 an observational study including a cohort of women whose pregnancy was monitored in the publically-funded health system in a central region of Catalonia. Women received individual educational counseling imparted, a dietary questionnaire was completed, and a urine sample collected for iodine determination at each trimester visit. Results: 633 (67.9%) women answered the questionnaire at all 3 visits. The percentage of women with a desirable UIC (≥150μg/L) increased from the first to the second trimester and remained stable in the third (p<0.001). Analysis of the relationship between UIC≥150 μg/L and the women’s dietary habits showed that the percentage with UIC≥150 μg/L increased with greater consumption of milk, fresh vegetables, and fruit in the first trimester, and the same was true for iodized salt use in all three trimesters and iodine supplementation in all three. Conclusion: During pregnancy increased intake of milk, iodized salt, and iodine supplements was associated with an increase in the UIC.

Following spinal cord injury (SCI), pathological reflexes develop that result in altered bladder function and sphincter dis-coordination, with accompanying changes in the detrusor. Bladder chemodenervation is known to ablate the pathological reflexes, but the resultant effects on the bladder tissue are poorly defined. In a rodent model of contusion SCI, we examined the effect of early bladder chemodenervation with botulinum toxin A (BoNT-A) on bladder histopathology and collagen deposition. Adult female Long Evans rats were given a severe contusion SCI at spi-nal level T9. The SCI rats immediately underwent open laparotomy and received detrusor injec-tions of either BoNT-A (10 U/animal) or saline. At 8 weeks post injury, the bladders were col-lected, weighed, and examined histologically. BoNT-A injected bladders of SCI rats (SCI-BoNT-A) weighed significantly less than saline injected bladders of SCI rats (SCI-saline) (241 ± 25 mg vs. 183 ± 42 mg; p<0.05). Histological analyses showed that SCI resulted in significantly thicker bladder walls due to detrusor hypertrophy and fibrosis compared to bladders from uninjured animals (339 ± 89.0 m vs. 193 ± 47.9 m; p<0.0001). SCI-BoNT-A animals had significantly thinner bladder walls compared to SCI-saline animals (202 ± 55.4 m vs. 339 ± 89.0 m; p<0.0001). SCI-BoNT-A animals had collagen organization in the bladder walls similar to that of uninjured animals. Detrusor chemodenervation soon after SCI appears to preserve bladder tissue integrity, by reducing the development of detrusor fibrosis and hypertrophy associated with SCI.

Pulmonary complications are frequently observed in patients with ulcerative colitis (UC), with large airway disease being the most prevalent manifestation. In this case study, we explore the potential for Immunosuppressant, a monoclonal antibody, to induce pulmonary hemorrhage—a side effect not previously documented with its use. The subject, a young male in his twenties with a six-year history of UC, tragically died suddenly. Found in a pool of blood without external injuries, extensive post-mortem examinations were required to determine the cause of death. The patient had been on biologic therapy, receiving Immunosuppressant intermittently over the past two years, including an infusion five days prior to death. External examination revealed bloody, pinkish foamy material expelling from his nose and mouth. An autopsy supported an atypical presentation of UC, while histopathology confirmed diffuse pulmonary hemorrhage, marked by edema and emphysematous changes. Additionally, there was a notable lymphomonocytic infiltration around the arterial walls, and signs of bronchiolitis and focal pleural fibrosis were evident. We concluded that the cause of death was Diffuse Alveolar Hemorrhage (DAH), directly associated with the recent administration of Immunosuppressant. This finding underscores the need for vigilant pulmonary monitoring in patients treated with monoclonal antibodies to promptly identify and manage potential fatal adverse reactions.

Urinary tract infections (UTIs) caused by Klebsiella pneumoniae can lead to severe clinical complications and even death. An alternative treatment option for infected patients is using bacteriophages (phages). In the present study, we isolated phage KP-1 from sewage water using K. pneumoniae as a host. Whole genome analysis indicated that the genome was a double-stranded linear 176,096-bp long DNA molecule with 41.8% GC content and did not contain virulence or antibiotic resistance genes. The inactivation potential of phage KP-1 was assessed in broth at an MOI of 1 and 10, and a maximum inactivation of 4.9 and 5.4 log CFU/mL was observed after 9 h, respectively. The MOI of 10 efficacy was also assessed in urine to evaluate the phage’s performance in an acidic environment. A maximum inactivation of 3.8 log CFU/mL was observed after 9 h. The results indicate that phage KP-1 could be used to control UTIs caused by K. pneumoniae; however, further studies using phage cocktails to broader the phage’s spectrum of activity and phages in micro- or nanocarriers to avoid the negative effect of the low pH of the urine on phage viability, are necessary.

Mouse wild-derived strains (WDS) combine the advantages of classical laboratory stocks and wild animals, and thus appear as promising tools for diverse biomedical and evolutionary studies. We employed 18 WDS representing three non-synanthropic species (Mus spretus, M. spicilegus, and M. macedonicus) and three house mouse subspecies (M. musculus musculus, M. m. domesticus, M. m. castaneus) which are all important human commensals to explore whether the number of major urinary protein (MUP) genes and their final protein levels in the urine are correlated with the level of commensalism. Contrary to expectations, MUP copy number (CN) and protein excretion in the strains derived from M. m. castaneus, which is supposed to be the strongest commensal, were not significantly different from the non-commensal species. Regardless of an overall tendency for higher MUP amounts in taxa with higher CN, there is no significant correlation at the strain level. Our study thus suggests that the expansion of the Mup cluster, which appeared before the house mouse diversification, is unlikely to facilitate commensalism with humans in the three house mouse subspecies. Finally, we found considerable variation among con(sub)specific WDS, warning against generalisations of results based on a few strains.

Urinary tract infections (UTIs) are the second most common bacterial infection with high recurrence rates. A major causative agent of UTIs is uropathogenic Escherichia coli (UPEC), which can form persistent biofilms on urothelial surfaces and/or urinary catheters. Biofilms are inherently tolerant to antimicrobials, making them difficult to eradicate. Ciprofloxacin hybrids functionalised with nitroxides have previously shown enhanced biofilm eradication activity in vitro. Here, we evaluate a ciprofloxacin di-nitroxide hybrid (CDN11), previously reported to have antibiofilm activity against UPEC, as a potential UTI therapeutic in various infection models. We report potent CDN11 activity against mature biofilms formed by cystitis strain UTI89 inside polyethylene catheters. In infected human bladder cell monolayers, CDN11 afforded a 3-log reduction in UPEC colony forming units (CFU) compared to controls, including intracellular bacteria. Infected mouse bladders carrying biofilm-like intracellular UPEC reservoirs had reduced bacterial burdens following treatment with CDN11 ex vivo. Activity trends for CDN11 were comparable throughout all models, indicating that our testing pipeline was robust. New antimicrobial development is arduous and requires large investments of time and money. The pipeline described here could be readily used in testing new compounds, fast tracking the development of novel UTI therapeutics.