European Association of Urology Guidelines on Urological Infections: Summary of the 2024 Guidelines.

BACKGROUND AND OBJECTIVE: Urological infections significantly impact the wellbeing and quality of life of individuals owing to their widespread occurrence and diverse clinical manifestations. The objective of the guidelines panel was to provide evidence-based guidance on the diagnosis, treatment, and prevention of urinary tract infections (UTIs) and male accessory-gland infections, while addressing crucial public health aspects related to infection control and antimicrobial stewardship. METHODS: For the 2024 guidelines on urological infections, new and relevant evidence was identified, collated, and appraised via a structured assessment of the literature. Databases searched included Medline, EMBASE, and the Cochrane Libraries. Recommendations within the guidelines were developed by the panel to prioritise clinically important care decisions. The strength of each recommendation was determined according to a balance between desirable and undesirable consequences of alternative management strategies, the quality of the evidence (including the certainty of estimates), and the nature and variability of patient values and preferences. KEY FINDINGS AND LIMITATIONS: Key recommendations emphasise the importance of a thorough medical history and physical examination for patients with urological infections. The guidelines stress the role of antimicrobial stewardship to combat the rising threat of antimicrobial resistance, providing recommendations for antibiotic selection, dosing, and duration on the basis of the latest evidence. CONCLUSIONS AND CLINICAL IMPLICATIONS: This overview of the 2024 EAU guidelines offers valuable insights into managing urological infections and are designed for effective integration into clinical practice. PATIENT SUMMARY: The European Association of Urology has issued an updated guideline on urological infections. The guidelines provide recommendations for diagnosis, treatment, and prevention, with a particular focus on minimising antibiotic use because of the increasing global threat of antimicrobial resistance.

Uncommon life history and winter spawning of common carp (Cyprinus carpio) in a natural thermal spring, under temperate climate.

Common carp female generally matures at age 4-5 years old and spawns between April and July under the temperate climate. Contrary to a range of 0-28 °C of temperate freshwaters, the water temperature of Lake Hévíz (Hungary, Central Europe), the largest natural bathable thermal lake in the world, varies between 26 and 35 °C seasonally. The specific environmental conditions (continuously warm water and its individual chemical composition, special nutrient base, lack of natural lakeside spawning substrate compared to usual spawning grounds, continuous high human disturbance, etc.) suggest that the carp population here may also differ in reproductive characteristics from their counterparts in surrounding waters. Our findings suggest that the self-sustaining dwarf common carp population of Lake Hévíz matures 2 to 4 years earlier (at the age of one) and spawns 1 to 3 months before (between February and April, at 27-30 °C water temperature) than carp typically do in the temperate zone (16-20 °C). Successful winter spawning was verified by rearing larvae from the collected eggs and in situ induced propagation.

Salivary miR-31-5p, miR-345-3p, and miR-424-3p Are Reliable Biomarkers in Patients with Oral Squamous Cell Carcinoma.

If not detected early, oral squamous cell carcinoma (OSCC) has very poor prognosis, emphasizing the need for reliable early diagnostics. Saliva is considered a promising surrogate biosample for OSCC detection, because it comes into contact with many cells of the tumor mass, providing a comprehensive sampling of tumor-specific biomolecules. Although several protein- and RNA-based salivary biomarkers have been proposed for the detection of OSCC, the results of the studies show large differences. Our goal was to clarify which salivary microRNAs (miRNA) show reliably high expression in the saliva of OSCC patients, to be used as cancer-specific biomarkers, and potentially as early diagnostic biomarkers. Based on a detailed literature search, we selected six miRNAs commonly overexpressed in OSCC, and analyzed their expression in saliva samples of cancer patients and controls by real-time quantitative PCR. Our results suggest that miR-345 and miR-31-5p are consistently upregulated salivary biomarkers for OSCC, and a three-miRNA panel of miR-345, miR-31-5p, and miR-424-3p can distinguish cancer and control patients with high sensitivity.

Biomarkers in urinary tract infections - which ones are suitable for diagnostics and follow-up?

Introduction: Urinary tract infections (UTIs) are one of the most common infections worldwide. Under special circumstances, clinicians must rely on laboratory findings, which might have a weak predicting value, misguiding the practitioners and leading to incorrect diagnosis and overuse of antibiotics. Therefore, there is an urgent need for reliable biomarkers in UTIs. Methods: We performed a literature search for biomarkers used in UTIs from January 1999 until May 2020. We used "urinary tract infection" and "biomarker" as the main key words in the PubMed, Medline and Cochrane databases. After peer review, we excluded the duplicates and identified the suitable articles, from which we collected the data and divided the available biomarkers into 5 groups: i) conventional markers; ii) promising, thoroughly studied biomarkers; iii) promising biomarkers that need further studies; iv) biomarkers of unknown significance; v) controversial, not useful markers. Results: We found 131 articles, mostly from the paediatric population. Neutrophil gelatinase-associated lipocalin (NGAL) and interleukins (IL) have a leading role in diagnosing and differentiating UTIs based on a lot of observational, comparative trials. Heparin Binding Protein (HBP), Lactoferrin (LF), Heat-Shock Protein-70 (HSP-70), Human Defensin-5 (HD-5), Lipopolysaccharide Binding Protein (LBP) and mass spectrometry studies are promising, but confirming data are lacking. The measurable components of the innate immune system and local host cell response could be appropriate biomarkers, but their significance is currently unknown. Conclusions: Conventional biomarkers for UTIs have low specificity. The use of urinary NGAL and interleukins could improve the sensitivity and specificity of laboratory diagnosis of UTIs.

Salivary IL-6 mRNA is a Robust Biomarker in Oral Squamous Cell Carcinoma.

Salivary IL-6 mRNA was previously identified as a promising biomarker of oral squamous cell carcinoma (OSCC). We performed a multi-center investigation covering all geographic areas of Hungary. Saliva from 95 patients with OSCC and 80 controls, all Caucasian, were collected together with demographic and clinicopathological data. Salivary IL-6 mRNA was quantified by real-time quantitative PCR. Salivary IL-6 protein concentration was measured by enzyme-linked immune-sorbent assay. IL-6 protein expression in tumor samples was investigated by immunohistochemistry. Normalized salivary IL-6 mRNA expression values were significantly higher (p < 0.001) in patients with OSCC (mean ± SE: 3.301 ± 0.885) vs. controls (mean ± SE: 0.037 ± 0.012). Differences remained significant regardless of tumor stage and grade. AUC of the ROC curve was 0.9379 (p < 0.001; 95% confidence interval: 0.8973-0.9795; sensitivity: 0.945; specificity: 0.819). Salivary IL-6 protein levels were significantly higher (p < 0.001) in patients (mean ± SE: 70.98 ± 14.06 pg/mL), than in controls (mean ± SE: 12.45 ± 3.29). Specificity and sensitivity of IL-6 protein were less favorable than that of IL-6 mRNA. Salivary IL-6 mRNA expression was significantly associated with age and dental status. IL-6 manifestation was detected in tumor cells and tumor-infiltrating leukocytes, suggesting the presence of a paracrine loop of stimulation. Salivary IL-6 mRNA is one of the best performing and clinically relevant biomarkers of OSCC.

Development of an antibody control system using phage display.

While chromatin immunoprecipitation has become a widely-used method in the field of transcription regulation studies, serious limitations connected to the complexity and relatively little standardization of the method serve as obstacles for its use in clinical research. In this paper we introduce a method for developing bacteriophage-based controls for the better standardization of the chromatin immunoprecipitation reactions. Random phage display libraries were selected with ChIP-grade antibodies for several rounds and individual monoclonal phages were isolated. These monoclonal phages can be propagated, characterized, capillary sequenced and if needed later cloned from in-silico data. Using such control tools allows for a better characterization of the immunoprecipitation stage needed for further clinical research in the field of chromatin-immunoprecipitation-based studies.

The Planktonic Core Microbiome and Core Functions in the Cattle Rumen by Next Generation Sequencing.

The cow rumen harbors a great variety of diverse microbes, which form a complex, organized community. Understanding the behavior of this multifarious network is crucial in improving ruminant nutrient use efficiency. The aim of this study was to expand our knowledge by examining 10 Holstein dairy cow rumen fluid fraction whole metagenome and transcriptome datasets. DNA and mRNA sequence data, generated by Ion Torrent, was subjected to quality control and filtering before analysis for core elements. The taxonomic core microbiome consisted of 48 genera belonging to Bacteria (47) and Archaea (1). The genus Prevotella predominated the planktonic core community. Core functional groups were identified using co-occurrence analysis and resulted in 587 genes, from which 62 could be assigned to metabolic functions. Although this was a minimal functional core, it revealed key enzymes participating in various metabolic processes. A diverse and rich collection of enzymes involved in carbohydrate metabolism and other functions were identified. Transcripts coding for enzymes active in methanogenesis made up 1% of the core functions. The genera associated with the core enzyme functions were also identified. Linking genera to functions showed that the main metabolic pathways are primarily provided by Bacteria and several genera may serve as a "back-up" team for the central functions. The key actors in most essential metabolic routes belong to the genus Prevotella. Confirming earlier studies, the genus Methanobrevibacter carries out the overwhelming majority of rumen methanogenesis and therefore methane emission mitigation seems conceivable via targeting the hydrogenotrophic methanogenesis.

Oral Health May Affect the Performance of mRNA-Based Saliva Biomarkers for Oral Squamous Cell Cancer.

Oral squamous cell carcinoma (OSCC) has a dismal 50% five-year survival rate, emphasizing the need to develop reliable and sensitive tools for early diagnosis. In this study we evaluated the performance of 7 previously identified, potential mRNA biomarkers of OSCC in saliva samples of Hungarian patients. Expression of the putative OSCC biomarkers (DUSP1, OAZ1, H3F3A, IL1B, IL8, SAT and S100P), 2 biomarkers of inflammation (IL6 and TNFα) and 8 putative normalizing genes was quantified from each sample using real-time quantitative PCR. In contrast with previous studies, the expression pattern of the 7 mRNA biomarkers was similar between OSCC patients and age-matched control patients in the Hungarian patient population. On the other hand, 5 of the 7 mRNA biomarkers were present at significantly higher levels in saliva samples of OSCC patients when compared to young control patients. The best biomarker combination could distinguish only the OSCC vs. young control patients, but not the OSCC vs. age-matched control patients. In conclusion, the significant differences between our results and previous studies, and the clinical characteristics of the patients suggest that inflammatory processes in the oral cavity may affect the performance of the 7 putative salivary mRNA biomarkers. Lastly, since IL6 mRNA was quantifiable in the majority of OSCC cases, but only in a few control samples, salivary IL6 mRNA may be utilized as part of a biomarker combination to detect OSCC.

Efficacy of intensive hand physical therapy in patients with systemic sclerosis.

OBJECTIVES: To evaluate the efficacy of a three-week period of complex and intensive hand physical therapy on hand function in patients with systemic sclerosis (SSc). METHODS: Thirty-one patients with SSc were treated. Hand stretching exercises, ergotherapy supplemented with thermal and mud baths, whirlpool therapy and soft tissue massage were daily used during a three-week period. The control SSc group (n=22) received similar management for their large joints leaving out their hands. The primary outcomes of this study were the Health Assessment Questionnaire (HAQ) and the Disabilities of the Arm, Shoulder and Hand (DASH). Hand Anatomic Index (HAI), Cochin Hand Function (CHFT) and clinical characteristics were also assessed before starting the therapy and six months afterwards. RESULTS: Six months after the investigation period, only the group receiving hand physical therapy showed improvement in HAQ and DASH scores compared to the baseline values (p<0.05). The improvement in median HAQ value (25%-75% quartiles) reached the clinical meaningful rate (baseline 1.125/0.625-1.625/ versus 0.75/0.25-1.5/ at six months). Visual analogue scales of global pain (p<0.01) and Raynaud's phenomenon (p<0.05) also had better results than at baseline. HAI, gripping strength and CHFT also showed some improvement, but did not reach the significance level of change by the end of the six-month observation period. CONCLUSIONS: The complex physical therapy caused favourable changes in both the HAQ and the DASH indicating that this particular program had some long-term beneficial effect on hand function in patients with SSc.

Evaluation of the Effect of Hévíz Mud in Patients with Hand Osteoarthritis: A Randomized, Controlled, Single-Blind Follow-Up Study.

BACKGROUND: Heat therapy is one of the most popular non-pharmacological treatments for osteoarthritis of the hand. OBJECTIVES: To investigate the therapeutic and chemical effects of Hévíz mud on patients with hand osteoarthritis. METHODS: We randomly assigned 47 patients with mild-to-moderate hand osteoarthritis to two groups. Patients in group 1 (n=23) received Hévíz mud applied directly to both hands, whereas patients in group 2 (n=24) also received mud to both hands, but nylon gloves separated the skin from the mud. Patients in both groups underwent five 20 minute treatment sessions per week for 3 weeks. The temperature of the mud was 42°C. Outcome measures were Visual Analogue Scale (VAS) scores, hand grip strength, the number of swollen and tender joints of the hand, the duration of morning joint stiffness, Health Assessment Questionnaire score, and EuroQoL Group 5-Dimension Self-Report Questionnaire score. The study parameters were evaluated at baseline, immediately after treatment, and after 16 weeks. RESULTS: Both groups showed improvement in nearly all assessed parameters at the end of treatment and at 16 weeks from the start of treatment. At the week 16 follow-up visit, the patient group directly treated with mud showed significantly better improvement in VAS for II and IV parameters and in swollen joint count in both hands compared to the nylon glove-mud group. CONCLUSIONS: Hévíz mud therapy significantly improved objective and subjective parameters in patients with hand osteoarthritis and had a beneficial effect on the patients' quality of life. Further studies are required to evaluate the chemical effects of the mud.

Herbicide-affected plant metabolism reduces virus propagation.

It has been previously shown that certain herbicides or plant extracts inhibited the viral infection. The goal of this study was to investigate the effect of Obuda pepper virus (ObPV) infection and herbicide or plant extract treatments on the photosynthetic processes of the host plants to get informations about the interactions of these factors. In Capsicum annuum-ObPV host-virus relations the virus infection slightly increased the activity of photosystem II (PSII), as it was supposed from fluorescence induction parameters. Chlorophyll content of leaves was also elevated probably due to virus-induced growth inhibition. The herbicide Stomp (active ingredient: pendimethalin) incorporated into the soil one week before planting (preplant treatment) together with virus infection even strengthened these effects in agreement with previous observations that this herbicide always did not prevent virus infection or reduce virus concentration in hosts. In ObPV-infected Nicotiana tabacum the structural changes showed similar tendency like in ObPV-infected C. annuum, but PSII efficiency did not significantly differ from that of the control. However, non-photochemical quenching (NPQ) increased because of the strongly decreasing CO2 fixation activity. Though simultaneous application of a water extract of Cirsium arvense shoot caused a little stronger inhibition of CO2 fixation, little loss in production was obtained due to significant reduction in virus concentration. In Solanum nigrum-ObPV relation the slightly increasing tendency of the values of actual PSII quantum efficiency could be related to the probably elevated ratio of reaction centre components (increased chlorophyll a/b ratio) in the thylakoids. Application of the herbicide Fusilade S (active ingredient: fluazifop-P-butyl) at 4-6 leaf stage as a post-emergence treatment practically prevented systemic virus infection and the virus-induced changes of photosynthesis are probably due to inhibiting the virus infection/replication process.