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The Diokno-Lapides Essay Contest was originally established in 1984 as the Jack Lapides Essay Contest on Urodynamic and Neurourology Research. Developed by Ananias Diokno to honor his mentor, Jack Lapides at the University of Michigan, it was funded by a grant from Marion Laboratories. The contest recognizes individuals doing outstanding work in neurourology and has been awarded yearly since 1985. Renamed the Diokno-Lapides Essay Contest in 2014, it has generated significant papers and discoveries in neurourology. Spanning 40 years, winners and other participants have attested to the contest's influence on their careers and its opportunities for networking and mentorship across the global urology community., (© 2023. The Author(s).)

Background: Alzheimer's disease (AD) is the most common form of dementia, accounting for 80% of all cases. Mild cognitive impairment (MCI) is a transitional state between normal aging and AD. Early detection is crucial, as irreversible brain damage occurs before symptoms manifest., Objective: This study aimed to identify potential biomarkers for early detection of AD by analyzing urinary cytokine concentrations. We investigated 37 cytokines in AD, MCI, and cognitively normal individuals (NC), assessing their associations with AD development., Methods: Urinary cytokine concentrations were measured in AD ( n  = 25), MCI ( n  = 25), and NC ( n  = 26) patients. IL6ST and MMP-2 levels were compared between AD and NC, while TNFRSF8, IL6ST, and IL-19 were assessed in AD versus MCI. Diagnostic models distinguished AD from NC, and in-silico analysis explored molecular mechanisms related to AD., Results: Significant perturbations in IL6ST and MMP-2 concentrations were observed in AD urine compared to NC, suggesting their potential as biomarkers. TNFRSF8, IL6ST, and IL-19 differed significantly between AD and MCI, implicating them in disease progression. Diagnostic models exhibited promising performance (AUC: 0.59-0.79, sensitivity: 0.72-0.80, specificity: 0.56-0.78) in distinguishing AD from NC. In-silico analysis revealed molecular insights, including relevant non-coding RNAs, microRNAs, and transcription factors., Conclusion: This study establishes significant associations between urinary cytokine concentrations and AD and MCI. IL6ST, MMP-2, TNFRSF8, IL6ST, and IL-19 emerge as potential biomarkers for early detection of AD. In-silico analysis enhances understanding of molecular mechanisms in AD. Further validation and exploration of these biomarkers in larger cohorts are warranted to assess their clinical utility., Competing Interests: The authors have no conflict of interest to report., (© 2023 – The authors. Published by IOS Press.)

Background: There are multiple methods to quantitatively assess limb lymphedema, but quantitative methods to assess external lymphedema in persons with head-and-neck lymphedema are quite limited. Quantification in this difficult condition currently uses multiple time-consuming head, face, and neck metric measurements, the accuracy of which is unclear. Thus, there is an important need for a new approach that is sufficiently convenient yet accurate to quantify head-and-neck lymphedema. The approach adopted was to use tissue dielectric constant (TDC) measurements that depend on tissue water, at neck and a submental area, and normalize these to TDC values at the forearm as a way to develop subject-independent indices. Methods and Results: TDC was measured in 60 self-reported healthy nonlymphedematous adults (34 female, 18-81 years, 18.5-45.7 Kg/m 2 ) at two neck sites and one arm site bilaterally and at a submental area. Neck-to-arm-index (NAI) and submental-to-arm-index (SAI) ratios were calculated. TDC values (mean ± standard deviation [SD]) for neck, submental, and arm were, respectively, 37.4 ± 6.9, 35.9 ± 7.7, and 30.1 ± 4.6. Mean NAI and SAI values were 1.253 ± 0.222 and 1.214 ± 0.296 respectively. Head-and-neck lymphedema thresholds calculated as mean + 2.5 SD were for NAI and SAI 1.80 and 1.95, respectively. Conclusions: An approach to help quantify and track head-and-neck lymphedema using TDC neck and/or submental values normalized to a person's forearm TDC values indicates threshold values between 1.80 and 1.95. These ratios, denoted as NAI and SAI, are suggested for use to detect and track changes in lymphedema status based on a patient's changing indices associated with lymphedema treatment.

Background Intrahepatic cholestasis of pregnancy (ICP) is the most common liver disorder of pregnancy. It occurs when bile flow from the liver is obstructed, causing bile acid to accumulate. ICP usually presents with itching that lasts for the remainder of pregnancy. Untreated ICP has been shown to increase the incidence of adverse outcomes for the baby, including respiratory distress, meconium aspiration, neonatal intensive care unit hospitalization, and stillbirth. The probability of these events increases when bile acid levels are greater than 40 mmol/L. The current standard of care for ICP patients is a combination of ursodeoxycholic acid by mouth and early delivery, as the risk of stillbirth due to ICP increases in the last weeks of pregnancy. ICP has been linked to preeclampsia and gestational diabetes; studies have shown that the occurrence of both diseases is greater when the baby is male. The purpose of this study was to investigate if the occurrence, timing of diagnosis, peak bile acid levels, or severity of itching is dependent on the baby's sex in mothers who had ICP. Methods An online question-set (survey) was offered to women who had had ICP and were members of three different online support groups. Results A total of 1,502 women responded for a total of 2,289 documented ICP pregnancies, in which there were 1,059 female babies and 1,230 male babies. Based on chi-square analysis of differences in frequencies, no difference was found between pregnancies with male versus female babies regarding the occurrence, timing of diagnosis, peak bile acid levels, or severity of itching in the evaluated population. However, surprisingly, the findings revealed that first-trimester diagnosis of ICP was made in 5.6% of the pregnancies, and there were 30 (1.8%) cases of ICP diagnosed in the absence of itching. Conclusions The findings suggest that the baby's sex does not impact the occurrence, timing of diagnosis, peak bile acid levels, or itch severity in ICP. The findings that 5.6% of the ICP pregnancies in the present study were diagnosed in the first trimester and 1.8% were diagnosed without the presence of itching reinforce the need to investigate these less common presentations. More studies are needed to determine if these findings are consistent across other populations., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Bartolone et al.)

Purpose: Given that more cancers are being diagnosed earlier and that treatment of cancer is improving, health issues of cancer survivors are becoming more common and apparent. Pelvic radiation therapy for the treatment of gynecological cancers can lead to long-term collateral damage to the bladder, a condition termed radiation cystitis (RC). Late sequelae may take many years to develop and include incontinence and pain as well as hematuria. RC is a rare but potentially life-threatening condition for which there are few management and treatment options., Methods: There are limited data in the literature regarding the effects of radiation on the bladder after gynecological cancer therapy and we hereby review the literature on cancer survivorship issues of pelvic radiation for gynecology literature., Results: Treatment options are available for patients with radiation-induced hemorrhagic cystitis. However, most treatments are risky or only effective for a short timeframe and no therapy is currently available to reverse the disease progress. Furthermore, no standardized guidelines exist describing preferred management options. Common therapies include hyperbaric oxygen therapy, clot evacuation, fulguration, intravesical instillation of astringent agents, and surgery. Novel developing strategies include Botulinum Toxin injections and liposomal-tacrolimus instillations. These treatments and strategies are discussed., Conclusions: In this review, we will present current and advanced therapeutic strategies for RC to help cancer survivors deal with long-term bladder health issues.

Background: This study examined the hypothesis that 26S proteasome dysfunction in human end-stage heart failure is associated with decreased docking of the 19S regulatory particle to the 20S proteasome. Previous studies have demonstrated that 26S proteasome activity is diminished in human end-stage heart failure associated with oxidation of the 19S regulatory particle Rpt5 subunit. Docking of the 19S regulatory particle to the 20S proteasome requires functional Rpt subunit ATPase activity and phosphorylation of the α-type subunits., Methods and Results: An enriched proteasome fraction was prepared from 7 human nonfailing and 10 failing heart explants. Native gel electrophoresis assessed docking of 19S to 20S proteasome revealing 3 proteasome populations (20S, 26S, and 30S proteasomes). In failing hearts, 30S proteasomes were significantly lower (P=0.048) by 37% suggesting diminished docking. Mass spectrometry-based phosphopeptide analysis demonstrated that the relative ratio of phosphorylated:non phosphorylated α7 subunit (serine250) of the 20S proteasome was significantly less (P=0.011) by almost 80% in failing hearts. Rpt ATPase activity was determined in the enriched fraction and after immunoprecipitation with an Rpt6 antibody. ATPase activity (ρmol PO4/μg protein per hour) of the total fraction was lowered from 291±97 to 194±27 and in the immunoprecipitated fraction from 42±12 to 3±2 (P=0.005) in failing hearts., Conclusions: These studies suggest that diminished 26S activity in failing human hearts may be related to impaired docking of the 19S to the 20S as a result of decreased Rpt subunit ATPase activity and α7 subunit phosphorylation.

Evidence shows that tobacco smoking interacts with development of rheumatic diseases. Increase in white cells count (leukocytosis) is frequently present, and in smokers, it is considered a biomarker of cardiovascular risk. Aim of the study is to evaluate this biomarker in smokers with rheumatic diagnosis. We carried out an observational study on 115 rheumatic outpatients (26 men and 89 women) divided into two groups according to their smoking habit: one composed of 56 smokers, the other of 59 not smokers. Diagnosis and common routinary clinical parameters were collected. In the total sample, smokers were 48.69%. Most common diagnosis was osteoarthritis (OA) (40.87% of the total); smokers in OA women were 36.11%, smokers in OA men were 54.55%. Second most common diagnosis was rheumatoid arthritis (RA) (23.48% of the total); smokers in RA women were 40.91%; smokers in RA men were 80%. OA smokers showed a significant increase (P < 0.05) in white cells count when compared with OA not smokers. Between RA smokers and not smokers, any clinical difference was found. RA subjects following regular pharmacological treatment in the last 2 months were 84.61%. OA patients treated with drugs in the last 2 months were only 22.2%. Results seem to confirm that smoking habit may influence the development as well as gender distribution of rheumatic diseases. They show also that in absence of pharmacological treatment in smokers affected by OA leukocytosis (biomarker of cardiovascular risk) is observed.

Background: Ischemic colitis is an uncommon complication in patients with systemic lupus erythematosus but may be precipitated by colonoscopy., Case Report: A 43-year-old female with systemic lupus erythematosus under treatment with immunosuppressive drugs and prednisone was submitted to colonoscopy because of a change in bowel habit. Apart from the presence of a small metaplastic polyp, colonoscopy showed only a few erythematosus areas in the sigma and left colon. Four hours after colonoscopy, the patient developed lower colic abdominal pain and mucous diarrhea followed by rectal bleeding from ischemic colitis. The patient was successfully treated with fluids, spasmolytic drugs, sodic heparin, antibiotics and enteral feeding., Conclusions: Awareness of the risk of this potential complication, secondary to colonoscopy, in patients with connective tissue disorders may lead to a prompt diagnosis and effective treatment, with a successful outcome.

The aim of the present study was to detect entheseal abnormalities by means of ultrasonography (US) in patients with psoriasis. We evaluated 24 patients with psoriasis who underwent clinical and ultrasonographic examination of both lower limbs at the calcaneal insertions of the Achilles tendons and at the flexor and extensor tendons of all fingers of the hand. Fourteen patients with psoriatic arthritis were used as controls. US was performed using a real-time scanner (ATL SDI 3000) with a 5-12 MHz linear array transducer. Longitudinal and transverse scans of the talocrural joints, Achilles tendons and both the flexor and extensor tendons of the fingers of both hands were obtained at rest and during active and passive movements. On clinical examination no entheseal site was abnormal, but on US examination 33% of patients showed abnormalities. In particular, six psoriasis patients (25%) who were asymptomatic showed effusion around the extensor tendon of the first digit of the left hand and around the extensor tendon of the third and fourth digits of both hands; two patients (8.3%) showed a hypoechoic nodular formation of the flexor tendon sheath of the left hand. We conclude that entheseal abnormalities not detected at clinical examination were present in 33% of patients with psoriasis who underwent US examination. Therefore, we suggest the routine use of ultrasonography in the early diagnosis and in treatment and follow-up of patients with tendon enthesopathy, since these factors may have implications for therapy.

We investigated the serum levels of both receptor activator of nuclear factor kappaB ligand (RANKL) and its decoy receptor osteoprotegerin (OPG) in postmenopausal healthy women after a 1-yr therapy with genistein, (n = 30; 54 mg/d), hormone replacement therapy (n = 30; 1 mg/d 17beta-estradiol combined with norethisterone acetate) and placebo (n = 30). By comparison with placebo, the soluble RANKL (sRANKL)/OPG ratio was lower in the genistein group (-69 +/- 7%; P < 0.01 vs. placebo 81 +/- 24%) and in hormone replacement therapy-treated women (-11 +/- 2%; P < 0.01 vs. placebo). A positive correlation (r = 0.63; P < 0.01) was found between 1-yr percentage change in sRANKL/OPG ratio and 1-yr change in urinary deoxypyridinoline, a bone resorption marker. A negative correlation was observed between 1-yr percentage change in sRANKL/OPG ratio and 1-yr change in femoral neck bone mineral density (r = -0.7; P < 0.01). Our findings suggest that the sRANKL-OPG system may mediate the beneficial effects of genistein on bone remodeling in postmenopausal women.

Objective: To determine the frequency of osteoporosis in a large cohort of women with rheumatoid arthritis (RA) and to investigate the main determinants of bone mineral density (BMD) and risk factors for vertebral fractures in this population., Methods: We recruited 925 consecutive female patients with RA at 21 Rheumatology Centers in Italy. For each patient pre-registered demographic, disease, and treatment-related variables were collected. BMD was measured at lumbar spine and proximal femur by dual x-ray absorptiometry technique. Collected variables underwent a univariate and multivariate statistical procedure. Osteoporosis was defined as BMD > -2.5 T score., Results: The frequency of osteoporosis in the whole sample was 28.8% at lumbar spine and 36.2% at femoral neck and increased linearly from Steinbrocker's functional stage I to IV (p = 0.0001). Patients with spinal or femoral osteoporosis were significantly older (p = 0.0001), had a lower body mass index (BMI) (p < 0.02), a significantly longer disease duration (p < 0.02) and a significantly higher Health Assessment Questionnaire (HAQ) score (p = 0.0001). These differences were significant, even after adjusting for age. Steroid use was associated with significantly lower lumbar and femoral BMD (p = 0.0001) even after adjusting for the main confounding covariates. Analysis of lateral spine radiographs revealed 74 women with at least one vertebral fracture. These women had a significantly lower lumbar and femoral BMD (p = 0.0001). The generalized linear model showed that steroid use, menopause, BMI, age, and HAQ were all significant independent predictors of lumbar and femoral BMD. The logistic procedure showed that age (OR 1.05, 95% CI 1.03-1.07), HAQ (OR 1.3, 95% CI 1.07-1.7), menopause (OR 1.9, 95% CI 1.1-3.2), use of steroids (OR 1.5, 95% CI 1.07-2.1), and BMI (OR 0.8, 95% CI 0.8-0.9) were significantly associated with the risk for osteoporosis. The only variables associated with an increased risk for vertebral fracture were age (OR 1.04, 95% CI 1.01-1.08), HAQ (OR 1.7, 95% CI 1.08-2.09), and cumulative steroid intake (OR for 1 g of prednisone 1.03, 95% CI 1.006-1.07)., Conclusion: To prevent osteoporosis and its dramatic complications in RA the therapeutic challenge is to preserve functional capacity using the lowest possible dosage of corticosteroids.

Background: Systemic sclerosis (SSc) is a multisystemic disease characterized by proliferation and swelling of endothelial cells and other disorders. Raynaud's phenomenon (RP) is a disturbance, with unknown pathogenesis, that may be a precursor to SSc. The aim of this study was to investigate possible alterations in the haemostatic system and to examine whether there is a circadian variation in haemostatic variables at the initial stage of SSc., Methods: In 20 patients with RP (in all patients secondary to SSc) and in 10 controls the levels of thrombomodulin (TM), beta-thromboglobulin (beta-TG), D-dimer (DD), tissue-type plasminogen activator (t-PA) and plasminogen activator-inhibitor (PAI-1) were measured in venous plasma samples taken at 9.00 and 14.00., Results: Only TM levels were found to be higher in patients than in controls. Moreover the PAI-I levels, in the patient group, showed a significant circadian rhythm (with peak values at 9.00). No significant circadian variations for the other parameters were detected., Conclusions: These data seem to indicate that in patients with RP there is an endothelial damage reflected by a significant elevation of the TM plasma level and a circadian variation in plasma PAI-1, which was higher in the morning. This observation may be an area worth exploring for its importance potential in the knowledge of Raynaud's phenomenon.