CCDC86 is a novel Ki-67-interacting protein important for cell division.

The chromosome periphery is a network of proteins and RNAs that coats the outer surface of mitotic chromosomes. Despite the identification of new components, the functions of this complex compartment are poorly characterised. In this study, we identified a novel chromosome periphery-associated protein, CCDC86 (also known as cyclon). Using a combination of RNA interference, microscopy and biochemistry, we studied the functions of CCDC86 in mitosis. CCDC86 depletion resulted in partial disorganisation of the chromosome periphery with alterations in the localisation of Ki-67 (also known as MKI67) and nucleolin (NCL), and the formation of abnormal cytoplasmic aggregates. Furthermore, CCDC86-depleted cells displayed errors in chromosome alignment, altered spindle length and increased apoptosis. These results suggest that, within the chromosome periphery, different subcomplexes that include CCDC86, nucleolin and B23 (nucleophosmin or NPM1) are required for mitotic spindle regulation and correct kinetochore-microtubule attachments, thus contributing to chromosome segregation in mitosis. Moreover, we identified CCDC86 as a MYCN-regulated gene, the expression levels of which represent a powerful marker for prognostic outcomes in neuroblastoma.

Chromosome clustering in mitosis by the nuclear protein Ki-67.

Ki-67 is highly expressed in proliferating cells, a characteristic that made the protein a very important proliferation marker widely used in the clinic. However, the molecular functions and properties of Ki-67 remained quite obscure for a long time. Only recently important discoveries have shed some light on its function and shown that Ki-67 has a major role in the formation of mitotic chromosome periphery compartment, it is associated with protein phosphatase one (PP1) and regulates chromatin function in interphase and mitosis. In this review, we discuss the role of Ki-67 during cell division. Specifically, we focus on the importance of Ki-67 in chromosome individualisation at mitotic entry (prometaphase) and its contribution to chromosome clustering and nuclear remodelling during mitotic exit.

Erectile and Ejaculatory Dysfunction Associated with Use of Psychotropic Drugs: A Systematic Review.

BACKGROUND: Sexual dysfunction may be a side effect of treatment with antipsychotics, antidepressants, and other psychotropic drugs. AIM: To review the evidence concerning male sexual dysfunctions in patients taking psychotropic drugs to provide specific information to nonpsychiatric physicians for the management of these dysfunctions. METHODS: A systematic search of Medline and Embase databases was performed up to October 15th, 2020. We included randomized controlled trials comparing the effects of psychotropic drugs versus placebo or versus another drug of the same class, for at least 5 weeks. OUTCOMES: We considered studies whose male population could be evaluated separately from the female population and with a separate analysis of the different phases of the male sex cycle. RESULTS: We included 41 studies in the final review. There was a significant association between sexual dysfunction and antidepressant drug therapy, compared to placebo (decreased libido OR 1.89, 95% CI:1.40 to 2.56, 22 series, 11 trials, 7706 participants; erectile dysfunction OR = 2.28, 95% CI: 1.31 to 3.97; 11 trials, 3008 participants; ejaculatory dysfunction OR = 7.31, 95% CI: 4.38 to 12.20,19 trials, 3973 participants). When the effects of selective serotonin reuptake inhibitors (SSRIs) were evaluated separately from those of serotonin/norepinephrine reuptake inhibitors (SNRIs), the use of SNRIs but not that of SSRIs was characterized by significantly higher odds of erectile dysfunction compared to placebo. Only limited data were found regarding the effects of antipsychotics on the phases of the male sexual cycle, as it was shown that aripiprazole and risperidone showed lower and higher odds for erectile or ejaculatory dysfunction, respectively, compared to other atypical antipsychotics. CLINICAL IMPLICATIONS: Treatment of male sexual dysfunction in patients taking psychotropics requires a basic knowledge of the different drugs that affect sexual function with different mechanisms. STRENGTHS & LIMITATIONS: The effects of psychotropic drugs on erectile function and ejaculation were evaluated separately. The great variability of the mechanisms of action makes it difficult to make comparisons between the effects of the different classes of psychotropic drugs. CONCLUSIONS: Administration of antipsychotics affects male sexual function with different mechanisms, although the increase in prolactin values associated with the administration of first-generation antipsychotics and some atypical, such as risperidone, seems to play a primary role in determining male sexual dysfunction. Most antidepressants cause decreased libido, ejaculatory and erectile dysfunction, however the administration of SNRIs appears to be possibly associated with a specific risk of erectile dysfunction. Trinchieri M, Trinchieri M, Perletti G, et al. Erectile and Ejaculatory Dysfunction Associated with Use of Psychotropic Drugs: A Systematic Review. J Sex Med 2021;18:1354-1363.

Urinary side effects of psychotropic drugs: A systematic review and metanalysis.

OBJECTIVE: To evaluate the effects of psychotropic drugs on bladder function. MATERIALS AND METHODS: A systematic review was carried out by searching PubMed and Embase databases for randomized controlled trials enrolling patients treated with psychotropic drugs with available information on treatment-related urinary disorders. RESULTS: A total of 52 studies was selected. In antidepressant therapy, bladder voiding symptoms, rather than storage symptoms, were more frequently observed. Pooled analysis demonstrated a higher odds ratio (OR) of voiding  disorders in comparison with placebo (OR: 3.30; confidence interval [CI]: 1.90-5.72; 7856 participants; p < 0.001). Odds for voiding dysfunction was higher for tricyclic antidepressants and for Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs) when compared to Selective Serotonin Reuptake Inhibitors (SSRIs). Treatment with antipsychotics was associated with heterogeneous urinary disorders  including emptying and storage disorders. OR for incontinence in patients with dementia taking  antipsychotics was higher than placebo (OR: 4.09; CI: 1.71-9.79, p = 0.002) with no difference between different atypical antipsychotics. Rate of voiding disorders was not different between conventional and atypical antipsychotics (OR: 1.64; CI: 0.79-3.39, p = 0.19), although quetiapine showed higher odds to cause voiding dysfunction than other atypical antipsychotics (OR: 2.14; CI: 1.41-3.26; p > 0.001). CONCLUSIONS: In patients taking tricyclic antidepressants or SNRIs, bladder voiding disorders, could be the side effects of therapy rather than symptoms of a urological disease. Patients treated with these drugs should be actively monitored for the appearance of urinary symptoms. Antipsychotic treatment is associated with various urinary side effects requiring a tailored approach.

Sexuality, Sexual Orientation and Chronic Prostatitis.

Chronic prostatitis (CP) is a common health condition in men. Albeight obvious, a relationship between microbial induced prostatic inflammation and sexual function has not been as thoroughly investigated. Aiming to investigate possible associations between sexuality/sexual orientation and chronic bacterial prostatitis, we retrospectively evaluated 1783 visits (2009-2019) owing to investigation of prostatitis-like symptoms and routine follow up. A total of 389 patients, provided information regarding sexual orientation and sexuality. The mean age was 45,5 years. According their report, 92.28% were heterosexual, 6.16% homosexual and 1.54% bisexual. Regarding sexuality, 26,6% reported multiple sexual partnerships while 73,4% reported single sexual partnerships. There was a statistically significant association between chronic bacterial prostatitis as initial diagnosis and having multiple sexual partnerships. In contrast, the association between CBP and sexual orientation was not statistically significant Similarly, no significant association between any therapy outcome and having multiple sexual partners was established. Our findings suggest a connection between sexual practices and the onset of CBP which should be further investigated in order to reach to scientific conclusions.

Lithogenic Potential of Ureaplasma in Chronic Prostatitis.

INTRODUCTION: The role of Ureaplasma spp. (UPs) in the pathogenesis of chronic prostatitis is debated. The lithogenic potential of UPs could be a risk factor for the development of chronic prostatitis. METHODS: A total of 143 patients with identification of UPs were retrospectively selected from a database including patients with prostatitis-like symptoms who were studied according to the same protocol including clinical, microbiological and microscopic evaluation, and transrectal prostate ultrasound. A control group of patients with negative UPs was considered including 393 with chronic bacterial prostatitis (CBP), 42 patients with Chlamydia trachomatis (CT), and 781 patients with chronic pelvic pain syndrome. UPs and Mycoplasma hominis (MH) were identified using a semiquantitative assay. RESULTS: Calcifications were observed more frequently in patients with UPs (64%) than in patients with CBP without UPs (39%), CT infection (37%), and chronic pelvic pain syndrome (29%) (p < 0.0001). UPs were isolated in VB1 alone in 35 patients (urethral UPs), in expressed prostatic secretion (EPS) or post-massage urine (VB3) or sperm in 77 patients (prostatic UPs) and associated with other pathogens in 31 patients (associated UPs). Calcifications were more frequent in prostatic UPs (71%) and associated UPs (73%) than in urethral UPs (34%). Mean NIH-CPSI scores were not significantly different between groups, although mean WBC counts of sperm of patients with urethral UPs were significantly lower than in patients with prostatic UPs (p = 0.000) and associated UPs (p = 0.002). CONCLUSIONS: UPs identification in the urogenital fluids is related to higher rates of prostate calcifications. The ability of UPs to promote the formation of calcifications could be related to the chronicization of prostate infection. In particular, the presence of UPs in VB3/EPS/sperm is associated with higher rates of calcifications and high WBC sperm counts, suggesting a partial or full causative role of UPs in the pathogenesis of this disease.

Levofloxacin for NIH Category II Chronic Bacterial Prostatitis: A Real-Life Study.

BACKGROUND: Mounting worldwide resistance trends make the use of fluoroquinolone (FQ) antibacterial agents increasingly difficult. This is felt more acutely in the case of urogenital infections, which are mainly caused by Gram-negative pathogens. For years, levofloxacin and other FQs have been the first-line drugs for treating National Institutes of Health (NIH) category II chronic bacteria prostatitis (CBP). Eradication rates achieved by levofloxacin in the frame of randomized trials vary greatly, ranging between 71 and 86%. OBJECTIVES: This was a retrospective observational study to investigate the efficacy of levofloxacin against CBP in a real-life setting (urological outpatient wards). METHODS: A database including the clinical records of >2,500 CBP patients was reviewed. Patients were selected based on strict inclusion criteria. They were treated for 4 weeks with 500 mg levofloxacin per day, alone or combined with other antibacterials. Besides standard urological procedures including the 4-glass test for pathogen isolation, international symptom questionnaires (the NIH Chronic Prostatitis Symptom Index [NIH-CPSI] and International Prostate Symptom Score [IPSS]) were administered. RESULTS: Pathogen eradication was achieved in 79% of the cases treated with levofloxacin as a single agent and 87.8% of patients who received a combination of levofloxacin and azithromycin. The 11% increase in the eradication rate in the latter group is statistically significant. In addition, the levofloxacin-azithromycin combination caused a significant decrease in prostate volume and significantly increased the bladder-voided volume. IPSS and NIH-CPSI values and the urinary peak flow rate decreased to a similar extent in both treatment groups. No adverse effects were reported by patients belonging to either treatment group. CONCLUSION: Levofloxacin retained its therapeutic efficacy in patients assessed in a real-life setting, and high eradication rates were attained when it was administered as a single agent. A combination of an FQ with azithromycin induced a significant improvement of eradication rates. This strategy may be an interesting option in both first-referral and relapsing cases, although caution should be exercised when patients are at risk of developing arrhythmias, tendinitis, or other adverse effects.

Multidisciplinary approach to prostatitis.

The modern clinical research on prostatitis started with the work of Stamey and coworkers who developed the basic principles we are still using. They established the segmented culture technique for localizing the infections in the males to the urethra, the bladder, or the prostate and to differentiate the main categories of prostatitis. Such categories with slight modifications are still used according to the NIH classification: acute bacterial prostatitis, chronic bacterial prostatitis, Chronic Pelvic Pain Syndrome (CPPS) and asymptomatic prostatitis. Prostatic inflammation is considered an important factor in influencing both prostatic growth and progression of symptoms of benign prostatic hyperplasia and prostatitis. Chronic inflammation/neuroinflammation is a result of a deregulated acute phase response of the innate immune system affecting surrounding neural tissue at molecular, structural and functional levels. Clinical observations suggest that chronic inflammation correlates with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and benign prostatic hyperplasia (BPH) and an history of clinical chronic prostatitis significantly increases the odds for prostate cancer. The NIHNIDDK classification based on the use of the microbiological 4- glasses localization test or simplified 2-glasses test, is currently accepted worldwide. The UPOINT system identifies groups of clinicians with homogeneous clinical presentation and is used to recognize phenotypes to be submitted to specific treatments. The UPOINTS algorithm implemented the original UPOINT adding to the urinary domains (U), psycho-social (P), organspecific (O), infection (I), neurological (N), muscle tension and tenderness (T) a further domain related to sexuality (S). In fact sexual dysfunction (erectile, ejaculatory, libido loss) has been described in 46-92% of cases with a high impact on the quality of life of patients with CP/CPPS. Prostatic ultrasound represents the most popular imaging test in the work-up of either acute and chronic prostatitis although no specific hypo-hyperechoic pattern has been clearly associated with chronic bacterial prostatitis and CPPS. Use of a digital-processing software to calculate the extension of prostatic calcification area at ultrasound demonstrated a higher percentage of prostatic calcification in patients with chronic bacterial prostatitis. Multiparametric Magnetic Resonance Imaging (mpMRI) is the current state-of-the art imaging modality in the assessment of patients with prostate cancer although a variety of benign conditions, including inflammation, may mimic prostate cancer and act as confounding factors in the discrimination between neoplastic and non-neoplastic lesions. Bacteria can infect prostate gland by: ascending the urethra, reflux of urine into the prostatic ducts, direct inoculation of bacteria through inserted biopsy needles or hematogenous seeding. Enterobacteriaceae are the predominant pathogens in acute and chronic bacterial prostatitis, but an increasing role of Enterococci has been reported. Many strains of these uropathogens exhibit the ability to form biofilm and multidrug- resistance. Sexually Transmitted Infections (STI) agents, in particular Chlamydia trachomatis and Mycoplasma genitalium, have been also considered as causative pathogens of chronic bacterial prostatitis. On the contrary the effective role in genital diseases of other "genital mycoplasmas" is still a much debated issue. Sexually Transmitted Infections agents should be investigated by molecular methods in both patient and sexual partner. "Next generation" investigations, such as cytokine analysis, cytological typing of immune cells could help stratifying the immune response. Epigenetic dysregulation of inflammatory factors should be investigated according to systemic and compartment-specific signals. The search for biomarkers should also include evaluation of hormonal pathways, as measurement of estrogen levels in semen. Antimicrobials are the first line agents for the treatment of bacterial prostatitis. The success of antimicrobial treatment depends on the antibacterial activity and the pharmacokinetic characteristics of the drug which must reach high concentrations in prostate secretion and prostate tissue. Acute bacterial prostatitis can be a serious infection with a potential risk for urosepsis For iInitial treatment of severely ill patients, intravenous administration of high doses of bactericidal antimicrobials, such as broad-spectrum penicillins, third-generation cephalosporins or fluoroquinolones, is recommended in combination with an aminoglycoside. Use of piperacillin-tazobactam and meropenem is justified in presence of multiresistant gramnegative pathogens. The antibiotic treatment of chronic prostatitis is currently based on the use of fluoroquinolones that, given for 2 to 4 weeks, cured about 70% of men with chronic bacterial prostatitis. For the treatment of Chlamydial prostatitis macrolides were shown to be more effective than fluoroquinolones, whereas no differences were observed in microbiological and clinical efficacy between macrolides and tetracyclines for the treatment of infections caused by intracellular pathogens. Aminoglycosides and fosfomycin could be considered as a therapeutic alternative for the treatment of quinolone resistant prostatitis. Use of alpha-blockers in CP/CPPS patients with urinary symptoms and analgesics +/- non steroidal anti-inflammatory drugs (NSAID), in presence of pain demonstrated a reduction of symptoms reduction and an improvement of quality of life, although long term use of NSAID is limited by side effect profile. However, the multimodal therapeutic regimen by contemporary use of alphablockers, antibiotics and anti-inflammatory showed a better control of prostatitis symptoms than single drug treatment. Novel therapeutic substances for the treatment of pain, such as the cannabinoid anandamide would be highly interesting to test. An alternative for the treatment of chronic prostatitis/chronic pelvic pain syndrome is phytotherapy, as primary therapy or in association with other drugs. Quercetin, pollen extract, extract of Serenoa repens and other mixtures of herbal extracts showed a positive effect on symptoms and quality of life without side effects. The association of CP/CPPS with alterations of intestinal function has been described. Diet has its effects on inflammation by regulation of the composition of intestinal flora and direct action on the intestinal cells (sterile inflammation). Intestinal bacteria (microbiota) interacts with food influencing the metabolic, immune and inflammatory response of the organism. The intestinal microbiota has protective function against pathogenic bacteria, metabolic function by synthesis of vitamins, decomposition of bile acids and production of trophic factors (butyrate), and modulation of the intestinal immune system. The alteration of the microbiota is called "dysbiosis" causing invasive intestinal diseases pathologies (leaky gut syndrome and food intolerances, irritable bowel syndrome or chronic inflammatory bowel diseases) and correlating with numerous systemic diseases including acute and chronic prostatitis. Administration of live probiotics bacteria can be used to regulate the balance if intestinal flora. Sessions of hydrocolontherapy can represent an integration to this therapeutic approach. Finally, microbiological examination of sexual partners can offer supplementary information for treatment.

The impact of prostate artery embolization (PAE) on the the physical history and pathophysiology of benign prostatic hyperplasia (BPH).

AIM: Prostate artery embolization (PAE) is a non invasive modality for the treatment of benign prostate hypertrophy (BPH) related lower urinary tract symptoms (LUTS). As a relatively new procedure, data determining the clinical success is somehow scarce. In the present article we examine the current clinical outcome measures in order to identify the most accurate. RESULTS: Current imaging outcome measures are consistent with clinical ones only in the group of patients with adenomatous- dominant BPH while are inconsistent in patients with small sized adenomas. CONCLUSIONS: Additional studies and/or evaluation tools are needed in order to provide accurate evaluation of clinical success in the subgroup of patients with non- adenomatous-dominant BPH while they may inspire new options and novel techniques for both BPH treatment and treatment-follow up.

Resistance of uropathogens to antibacterial agents: Emerging threats, trends and treatments.

Urinary tract infections are among the most common infectious diseases in humans. Today, resistance to nearly all antimicrobial classes is dramatically growing, and extremely drug-resistant or even pan-drug resistant pathogens are increasingly isolated around the world. It is foreseen that in the next decades the world will be facing a major medical emergency generated by the rapid spread of pathogens carrying resistance determinants of unprecedented power. Carbapenemase-producing Enterobacteriaceae, multidrug- resistant Enterococci and fluoroquinolone resistance determinants in both Gram-negative and Gram-positive uropathogens are among the greatest emergencies. In this article, the major emerging threats of particular interest to urologists are reviewed, worldwide resistance trends are illustrated, and novel and older - but still active - recommended drugs are summarized.

A rubber tube in the bladder as a complication of autoerotic stimulation of the urethra.

Self-insertion of foreign bodies in the urethra is most commonly associated with sexual or erotic arousal of adolescents with mental health disorders. Rarely it may practiced by healthy adults for masturbation. Migration of foreign bodies used for the abovementioned purpose from the urethra to adjacent organs is a relatively uncommon urologic problem that may cause serious complications which arose tardive. Presentation includes a variety of acute or chronic symptoms that depend of the underlying complications. The method of extraction depends on the shape, size and nature of the object and should be tailored according to the condition of the patient. In the present article we present a case of a rubber tube inserted to the urethra for erotic arousal purposes which migrated to the bladder during masturbation.

Lymphoepithelioma-like carcinoma of the bladder: A case report.

type of low differentiated carcinoma of the nasopharyngeal region characterized by marked infiltration of lymphocytes in the area involved by tumor. However, carcinomas with this peculiar morphologic feature have been also described in various anatomic locations and they are generally designated «lymphoepithelioma-like carcinomas¼. Those of the urinary bladder are uncommon as they account of 0.4%-1.3% of all bladder carcinomas. They may coexist with the conventional urothelial carcinoma. Given their rarity, there is poor information regarding their behaviour. Here we present a new case of lymphoepithelioma-like carcinoma in the bladder and we discuss its characteristics and prognosis.

Treatment of urethral strictures with balloon dilation: A forgotten tale.

Urethral stricture is a common condition that can lead to serious complications such as urinary infections and renal insufficiency secondary to urinary retention. Treatment options include catheterization and dilation, urethroplasty and endoscopic internal urethrotomy as well. Although treatment option depends on the type, length and aetiology of stricture, the choice can be influenced to varying degrees by the simplicity of the method, the preferences of the patient the available accoutrements and the patient health condition. Both urethroplasty and endoscopic internal urethrotomy require anaesthesia and thus are not suitable for many elder and unfit for surgical treatment patients. On the other hand, dilations are easy to perform in every day clinical practice however they have been associated with iatrogenic urethral trauma. In contrast, balloon dilation under vision dilates by radial application of forces against the stricture, avoiding the potentially shearing forces associated with sequential rigid dilation. Since it reduces the possibility of an iatrogenic urethral trauma and the subsequent spongiofibrosis may lead into improved therapeutic outcomes. In this report we describe a technique for the treatment of urethral strictures with balloon dilation in elder and unfit for surgical treatment patients.

Cell Cycle-Specific Protein Phosphatase 1 (PP1) Substrates Identification Using Genetically Modified Cell Lines.

The identification of protein phosphatase 1 (PP1) holoenzyme substrates has proven to be a challenging task. PP1 can form different holoenzyme complexes with a variety of regulatory subunits, and many of those are cell cycle regulated. Although several methods have been used to identify PP1 substrates, their cell cycle specificity is still an unmet need. Here, we present a new strategy to investigate PP1 substrates throughout the cell cycle using clustered regularly interspersed short palindromic repeats (CRISPR)-Cas9 genome editing and generate cell lines with endogenously tagged PP1 regulatory subunit (regulatory interactor of protein phosphatase one, RIPPO). RIPPOs are tagged with the auxin-inducible degron (AID) or ascorbate peroxidase 2 (APEX2) modules, and PP1 substrate identification is conducted by SILAC proteomic-based approaches. Proteins in close proximity to RIPPOs are first identified through mass spectrometry (MS) analyses using the APEX2 system; then a list of differentially phosphorylated proteins upon RIPPOs rapid degradation (achieved via the AID system) is compiled via SILAC phospho-mass spectrometry. The "in silico" overlap between the two proteomes will be enriched for PP1 putative substrates. Several methods including fluorescence resonance energy transfer (FRET), proximity ligation assays (PLA), and in vitro assays can be used as substrate validations approaches.

Transradial Prostatic Artery Embolization as a Salvage Procedure in a Patient With Severe Deformities and Refractory Hematuria of Prostatic Origin.

Benign prostatic hyperplasia is a common condition causing urinary symptoms in older men. It can sometimes lead to hematuria of prostatic origin, due to increased vascularity of the enlarged gland. If this type of hematuria is severe and refractory to conservative measures, it can be life-threatening. Prostatic artery embolization (PAE) serves as a minimally invasive alternative to traditional surgical interventions, particularly in patients with comorbidities and contraindications to surgery. We present a case of a 79-year-old male with refractory hematuria of prostatic origin (RHPO), multiple comorbidities, and significant deformities of the left upper and both lower limbs. The patient was treated with PAE via the right radial artery, a less common approach in interventional radiology. The procedure was successful and led to a complete resolution of hematuria, with no complications. This report highlights the importance of adapting treatment for complex patients and shows that PAE can be safe and effective in such cases.

Association Between Soluble Cell Adhesion Molecules (sP-Selectin, sE-Selectin, and sICAM-1) and Antibodies Against the Antigens of Proteus mirabilis in Rheumatoid Arthritis Patients.

Objective The purpose of this study was to examine the association between the serum concentration of soluble cell adhesion molecules (CAMs) and antibodies against antigens of Proteus mirabilis (P. mirabilis) in rheumatoid arthritis (RA) patients, taking into consideration the implication of P. mirabilis in the etiopathogenesis of RA. Methods The serum levels of soluble P-selectin (sP-selectin), soluble E-selectin (sE-selectin), and soluble intercellular adhesion molecule-1 (sICAM-1) were determined by sandwich enzyme-linked immunosorbent assay (ELISA) in 59 RA patients and 36 healthy controls. Using the same ELISA method, the serum levels of class-specific antibodies against hemolysin (HpmB), urease C (UreC), and urease F (UreF) enzymes of P. mirabilis were also measured.  Results In this study, increased levels of sP-selectin and sICAM-1 were observed in RA patients, while the levels of sE-selectin were increased in comparison with healthy controls but did not present a statistically significant difference. Moreover, increased levels of antibodies against HpmB, UreC, and UreF of P. mirabilis were found. Additionally, it was observed that the sE-selectin levels presented a significant correlation with IgG antibodies against the UreF antigen (there is no corresponding antigen in human tissue) in all the RA patients. A statistically significant correlation was observed between levels of soluble CAMs and antibodies against P. mirabilis in the different subgroups. Conclusion The observed correlation between soluble CAMs and antibodies against antigens of P. mirabilis, specifically in the subgroup of biologic therapy, indicates that P. mirabilis exists and provokes refractory in the treatment of RA.

Psychological and sexological assessment of patients with chronic prostatitis.

PURPOSE: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is characterized by a multiform clinical presentation requiring a differentiated treatment based on different phenotypes including the psychosocial and sexual domains. The aim of this study was assessing the complex correlations between somatic, psychological, and sexual symptoms of CP/CPPS patients. MATERIALS AND METHODS: We performed a cross-sectional study on patients attending a Prostatitis Clinic. Patients were administered the following questionnaires: National Institutes of Health- Chronic Prostatitis Symptom Index (NIH-CPSI), International Prostate Symptom Score (IPSS), International Index of Erectile Function (IIEF), Premature Ejaculation Diagnostic Tool (PEDT), Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder 7-item (GAD-7), Oxford Happiness Questionnaire (OHQ), and Temperament Evaluation of Memphis, Pisa, Paris and San Diego Autoquestionnaire (TEMPS-A). RESULTS: Linear regression analyses show highly significant correlations between scores of the NIH-CPSI and the scores of the GAD-7, PHQ-9 and OHQ psychometric questionnaires. IPSS scores correlate significantly with the psychometric scores only when a non-parametric analysis is performed. IIEF and PEDT sexual function scores did not correlate with any of the psychometric tests. NIH-CPSI scores correlate positively with most of the TEMPS-A profiles but the hyperthymic profile correlated negatively with the total and QoL NIH-CPSI and with PEDT scores. CONCLUSIONS: Scores measuring anxiety, depression, and psychological well-being in patients with CP/CPPS are strictly correlated with prostatitis-like symptoms although they are poorly correlated with symptoms of prostatism, as measured by IPSS, and not correlated with scores of sexual dysfunctions, as measured by IIEF and PEDT. A hyperthymic temperament may increase resilience against the disease.

Ki-67 is necessary during DNA replication for fork protection and genome stability.

BACKGROUND: The proliferation antigen Ki-67 has been widely used in clinical settings for cancer staging for many years, but investigations on its biological functions have lagged. Recently, Ki-67 has been shown to regulate both the composition of the chromosome periphery and chromosome behaviour in mitosis as well as to play a role in heterochromatin organisation and gene transcription. However, how the different roles for Ki-67 across the cell cycle are regulated and coordinated remain poorly understood. The progress towards understanding Ki-67 function have been limited by the tools available to deplete the protein, coupled to its abundance and fluctuation during the cell cycle. RESULTS: Here, we use a doxycycline-inducible E3 ligase together with an auxin-inducible degron tag to achieve a rapid, acute and homogeneous degradation of Ki-67 in HCT116 cells. This system, coupled with APEX2 proteomics and phospho-proteomics approaches, allows us to show that Ki-67 plays a role during DNA replication. In its absence, DNA replication is severely delayed, the replication machinery is unloaded, causing DNA damage that is not sensed by the canonical pathways and dependent on HUWE1 ligase. This leads to defects in replication and sister chromatids cohesion, but it also triggers an interferon response mediated by the cGAS/STING pathway in all the cell lines tested. CONCLUSIONS: We unveil a new function of Ki-67 in DNA replication and genome maintenance that is independent of its previously known role in mitosis and gene regulation.

Serenoa repens extract additionally to quinolones in the treatment of chronic bacterial prostatitis. The preliminary results of a long term observational study.

INTRODUCTION: Chronic prostatitis displays a variety of symptoms (mainly local pain exhibiting variability in origin and intensity). The purpose of this article is to briefly present the preliminary results of our study examining the role of phytotherapeutic agents in the treatment of chronic prostatitis patients. MATERIALS AND METHODS: The study included in total fifty-six consecutive patients who visited the outpatient department. Subjects were randomized into two groups. Subjects in the first group (28 patients) received prulifloxacin 600 mg for 15 days, while subjects in the second group (28 patients) received prulifloxacin 600 mg for 15 days and Serenoa repens extract for 8 weeks. The response was tested using laboratory and clinical criteria. RESULTS: We found statistically significant differences between the two groups regarding pain regression and no statistically significant regarding bacterial eradication. Moreover however while sexual dysfunction improvement was equally achieved in both groups, improvement of urinary symptoms was more evident in the 2nd group especially after the completion of the antibiotic treatment. CONCLUSIONS: Serenoa repens extract for 8 weeks seems to improve prostatitis related pain. Further randomized, placebo-controlled studies are needed to substantiate safer conclusions.

Percutaneous thrombin injection under contrast-enhanced ultrasound guidance to control active extravasation not associated with pseudoaneurysm.

The technique of percutaneous thrombin injection (PTI) under contrast-enhanced ultrasound (CEUS) guidance for control of acute hemorrhage-active extravasation not associated with pseudoaneurysm is demonstrated in three cases: 1) Massive spontaneous retroperitoneal hematoma in a patient with multiple comorbidities. Contrast-enhanced computed tomography (CT) showed extensive active extravasation, which was only partially controlled by transarterial embolization. CEUS was performed in the angiography suite. Contrary to unenhanced US and colour Doppler US (CDUS), CEUS confirmed persistent extravasation; CEUS-guided PTI was performed immediately thereafter. 2) Large rectus sheath hematoma in a patient on anticoagulant therapy. Contrast-enhanced CT and unenhanced US/CD could not definitely diagnose extravasation. CEUS clearly showed extravasation and was used for guidance of PTI. 3) Chest wall hematoma complicating central venous catheter placement in a patient with coronavirus on anticoagulant therapy. CDUS was inconclusive. CEUS was performed at the bedside, clearly showed active extravasation, and was used for guidance of PTI. In all three cases, post-PTI CEUS confirmed the absence of residual enhancement of the hematomas, and the hemodynamic status of the patients improved. PTI appears to be effective in selected cases of hematomas associated with active extravasation. In this context, CEUS may be the most suitable modality for guidance and for an immediate evaluation of the treatment effect.