Purpose: Cardiovascular disease (CVD) is one of the leading causes of death, accounting for one-third of all deaths worldwide. Patients with CVD are three times more likely to complain of sexual dysfunction than healthy people. Causes of sexual dysfunction in patients with CVD include physical/mental changes and drug side effects. The prevalence of sexual dysfunction in patients with CVD has been estimated to be up to 89%. Ordinary treatments such as pharmacotherapy cannot effectively reduce sexual problems. Therefore, sexual rehabilitation has a broad spectrum, including exercise therapy such as pelvic floor muscle treatment, appropriate counseling, a multidisciplinary approach, and partner rehabilitation. In this study, systematic review and meta-analysis was performed to investigate the effect of sexual rehabilitation on sexual problems in patients with CVD. Materials and Methods: Comprehensive literature searches were conducted using MEDLINE, Cochrane Library electronic database, and EMBASE through June 2022. Questionnaire scores at the end point as outcomes of the study were recorded as were standardized mean difference (SMD) with their 95% confidence intervals (CIs). Meta-regression analysis was conducted for each moderator. We performed a risk of bias evaluation for included studies using the RoB 2 tool. Results: The overall SMD in the meta-analysis for sexual rehabilitation versus no-sexual rehabilitation was 0.430 (95% CI, 0.226–0.633). There was a statistical difference between groups. SMD changes were 0.674 (95% CI, 0.308–1.039) at one month and 0.320 (95% CI, 0.074–0.565) at six months. The regression analysis with all variables (number of patients, study duration, and questionnaire types) revealed no significance. Conclusions This study indicates that sexual rehabilitation is an effective method with high therapeutic potential for sexual dysfunction of patients with CVD. However, for clinical application, well-designed studies with many patients should be conducted in the future and the standardization of rehabilitation protocols is required.

Purpose: To detect elements governing the pathogenesis of diabetic cystopathy (DC), mRNA sequencing was carried out for bladder tissues from normal rats and those with induced diabetes mellitus (DM). This research therefore offers possible underlying molecular pathways for the advancement of DC in relation to differential mRNA expression, together with visceral functional and architectural alterations noted in individuals with this condition. Methods: An intraperitoneal injection of streptozotocin (STZ) was utilized to provoke DM in male Sprague-Dawley rats. Dysregulation and significant variations between normal rats and those with induced DM were then identified by a fold change of ≥ 1.5 with a false discovery rate P < 0.05. Hierarchical clustering/heat map and Gene Ontology/DAVID reference sources were generated. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and protein-protein interaction analysis were then performed. Results: The diabetic rodent group exhibited a greater residual urine volume (4.0 ± 0.4 mL) than their control counterparts (0.7 ± 0.2 mL, P < 0.01) at 12 weeks after diagnosis of diabetes. Expression analysis revealed 16 upregulated and 4 downregulated genes in STZDM bladder samples. A notable increase in expression was seen in PTHLH, TNFAIP6, PRC1, MAPK10, LOC686120, CASQ2, ACTG2, PDLIM3, FCHSD1, DBN1, NKD2, PDLIM7, ATF4, RBPMS2, ITGB1 and HSPB8. A notable decrease in expression was seen in SREBLF1, PBGFR1, PBLD1 and CELF1. Major genetic themes associated with mRNA upregulation and downregulation ware identified via Gene Ontology analysis and KEGG pathways. Protein to protein interaction analysis detected PDLIM3, PDLIM7, ITGB1, ACTG2 as core high frequency nodes within the network. Conclusions Changes in mRNA expression together with biological process and pathways that contribute to the etiologies underlying visceral impairment of the bladder in DM are evident. Our strategy is promising for recognizing mRNAs exclusive to the bladder in DM that might offer useful targets for diagnosis and treatment.

Purpose: Ischemia of the bladder can occur if neovascular formation cannot keep pace with hypoxia induced by chronic bladder outlet obstruction (BOO). The aim of this study was to examine changes in angiogenesis growth factor expression generated by chronic BOO in a rat model of underactive bladder. Methods: Twenty female Sprague-Dawley rats aged 6 weeks were assigned to 4 groups (5 rats per group). Group 1 was the control. Group 2 underwent sham surgery. The rats in groups 3 and 4 underwent BOO and were followed up for 1 week and 8 weeks. Cystometry was carried out together with bladder tissue analysis at 1 week and 8 weeks postoperatively. Real-time polymerase chain reaction (PCR) assays were conducted to determine the expression level of angiogenesis-related growth factors. A hypoxia signaling pathway PCR array was additionally carried out. Results: The group that underwent BOO for 8 weeks showed abnormal bladder function, with a diminished intercontraction interval, decreased maximal voiding pressure, and higher volume of residual urine (P<0.05). Hypoxia-inducible factor-1 alpha expression was elevated in this group. The expression levels of vascular endothelial growth factor (VEGF) and VEGF receptor messenger RNA (mRNA) in the BOO group were comparable to those in the control group. However, angiotensin/tie receptor mRNA expression levels increased at 1 week after BOO, but decreased at 8 weeks after BOO. In animals that underwent BOO, fewer blood vessels exhibited positive immunofluorescent staining for von Willebrand factor. Alterations were also seen in the hypoxia signaling pathway PCR array. Conclusions In a rat model of underactive bladder caused by surgical BOO, reduced angiopoietin expression was demonstrated. This observation might underlie visceral ischemia and fibrosis associated with the procedure. The findings of this study might offer an improved understanding of the disease processes underlying BOO and facilitate selection of the appropriate time to repair the organ in this condition.

Purpose: Men with diabetes mellitus (DM) often present with severe erectile dysfunction (ED). This ED is less responsive to current pharmacological therapies. If we know the upregulated or downregulated genes of diabetic ED, we can inhibit or enhance the expression of such genes through RNA or gene overexpression. Methods: To investigate gene changes associated with ED in type 1 DM, we examined the alterations of gene expression in the cavernosum of streptozotocin-induced diabetic rats. Specifically, we considered 11,636 genes (9,623 upregulated and 2,013 downregulated) to be differentially expressed in the diabetic rat cavernosum group (n=4) compared to the control group (n=4). The analysis of differentially expressed genes using the gene ontology (GO) classification indicated that the following were enriched: downregulated genes such as cell cycle, extracellular matrix, glycosylphosphatidylinositol-anchor biosynthesis and upregulated genes such as calcium signaling, neurotrophin signaling, apoptosis, arginine and proline metabolism, gap junction, transforming growth factor-β signaling, tight junction, vascular smooth muscle contraction, and vascular endothelial growth factor (VEGF) signaling. We examined a more than 2-fold upregulated or downregulated change in expression, using real time polymerase chain reaction. Analysis of differentially expressed genes, using the GO classification, indicated the enrichment Results: Of the 41,105 genes initially considered, statistical filtering of the array analysis showed 9,623 upregulated genes and 2,013 downregulated genes with at least 2-fold changes in expression (P<0.05). With Bonferroni correction, SLC2A9 (solute carrier family 2 member 9), LRRC20 (leucine rick repeat containing 20), PLK1 (polo like kinase 1), and AATK (apoptosis-associated tyrosine kinase) were all 2-fold changed genes. Conclusions This study broadens the scope of candidate genes that may be relevant to the pathophysiology of diabetic ED. In particular, their enhancement or inhibition could represent a novel treatment for diabetic ED.

Background: Hypoxia damages the bladder wall and contributes to the initiation of bladder dysfunction. The change of hypoxia is not well known in impaired bladder contractility caused by long-term bladder outlet obstruction (BOO). We aimed to find out whether hypoxia of bladder tissue is present and what signaling mechanisms are involved in the decompensated bladder in BOO. Methods: Twenty 6-week-old female Sprague-Dawley rats were divided into 2 groups, 10 rats each: group 1, sham operation; group 2, BOO for 8 weeks. Eight weeks after the onset of BOO, we did cystometric evaluation and processed polymerase chain reaction (PCR) array for hypoxia pathway using bladder tissues. The PCR array consists of 84 genes known to be involved in the hypoxic response, cell differentiation, and metabolism. We did quantitative PCR (qPCR) and immunohistochemical staining of bladder tissue for hypoxia. Results: Eight genes were at least 2-fold upregulated and 3 genes were at least 2-fold downregulated in BOO group, compared with the sham operation group. The up-regulated genes (fold change) belonging to the hypoxia-inducible factor (HIF) 1 interactor included Cdkn2a (11.0), and the down-regulated genes belonging to HIF and co-transcription factors included Hif3a (−39.6) and Per1 (−5.1) by BOO. Genes influenced each other by means of TGFβ1, TNF, and TP53. Conclusion Hypoxia genes were increased in impaired contractility because of long-term BOO. The gene expression profiles could explain the molecular mechanisms of hypoxia in impaired contractility because of long-term BOO.

Purpose: Raised cerebral titers of acetylcholine have notable links with storage symptomatology related to lower urinary tract symptoms. The hippocampus contributes to the normal control of continence in the majority of instances (circuit 3). Owing to synaptic connections with other nerve cells, acetylcholine affects the micturition pathway via the liberation of additional cerebral neurotransmitters. Despite the fact that cerebral serotonin is a key inhibitor of reflex bladder muscle contractions, the influence of acetylcholine on its liberation is poorly delineated. The current research was conducted in order to explore the role of acetylcholine in serotonin liberation from sections of rat hippocampus in order to improve the comprehension of the relationship between cholinergic and serotonergic neurons. Methods: Hippocampal sections from 6 mature male Sprague-Dawley rats were equilibrated over a 30-minute period in standard incubation medium so as to facilitate [3H]5-hydroxytryptamine (5-HT) uptake. The cerebral neurotransmitter, acetylcholine, was applied to the sections. Aliquots of drained medium solution were utilized in order to quantify the radioactivity associated with [3H]5-HT liberation; any alterations in this parameter were noted. Results: When judged against the controls, [3H]5-HT liberation from the hippocampal sections remained unaltered following the administration of acetylcholine, implying that this agent has no inhibitory action on this process. Conclusions Serotonin liberation from murine hippocampal sections is unaffected by acetylcholine. It is postulated that the bladder micturition reflex responds to acetylcholine through its immediate cholinergic activity rather than by its influence on serotonin release. These pathways are a promising target for the design of de novo therapeutic agents.

Purpose: The lower urinary tract is believed to be centrally regulated with the involvement of a range of neurotransmitters. The parasympathetic excitatory input to the urinary bladder is suppressed when the serotonergic system is activated, and thereby voiding is blocked. In healthy people, continence is usually underpinned by hippocampal formation (circuit 3). In order to advance knowledge of how serotoninergic neurons and additional nerve fibers were correlated, the purpose of the present work was to research how the discharge of serotonin from hippocampal slices was affected by different neurotransmitters in rat models. Methods: The adopted procedure involved administration of the central neurotransmitters acetylcholine, norepinephrine, dopamine, N-methyl-D-aspartate (NMDA), gamma-aminobutyric acid (GABA), glycine, and neuropeptide Y as well as monitoring of the alterations in the discharge of [3H]5-hydroxytryptamine (5-HT). Furthermore, to determine whether the effect of the neurotransmitters was influenced by interneuron, tetrodotoxin was also employed. Results: Acetylcholine (10-5M) did not alter [3H]5-HT discharge, whereas more 5-HT was discharged from the hippocampal slices of rats under stimulation by norepinephrine (10-5M) as well as dopamine (10-5M) and tetrodotoxin (10-6M) did not inhibit the discharge. By contrast, tetrodotoxin inhibited the discharge of [3H]5-HT that was exacerbated by NMDA (10-4M). Meanwhile, compared to control, GABA (10-5M), glycine (10-5M), or neuropeptide Y (10-6M) did not alter the [³H]5-HT discharge. Conclusions From the research findings, it can be concluded that 5-HT discharge from rat hippocampus is enhanced by norepinephrine and dopamine through direct effect on the 5-HT neuronal terminal. By contrast, 5-HT discharge is intensified by NMDA by activating interneurons.

Purpose: Prostate cancer (PCa) incidence is affected by aging phenomenon and performance of screening test. In United States, PCa incidence is affected by period effect of U.S. Preventive Services Task Force (USPSTF) recommendation. However, no study has reported the effect of USPSTF recommendation or aging phenomenon on PCa incidence in South Korea. Thus, the objective of this study was to investigate effects of age, period, and birth cohort on PCa incidence using age-period-cohort analysis. Materials and Methods: Annual report of cancer statistics between 2003 and 2013 from National Health Insurance Service (NHIS) in South Korea for the number of PCa patients and Korean Statistical Information Service (KOSIS) data between 2003 and 2013 from national statistics in South Korea for the number of Korean male population were used. Age-period-cohort models were used to investigate effects of age, period, and birth cohort on PCa incidence. Results: Overall PCa incidence in South Korea was increased 8.8% in annual percentage (95% confidential interval, 6.5 to 11.2; p < 0.001). It showed an increasing pattern from 2003 to 2011 but a decreasing pattern from 2011 to 2013. Age increased the risk of PCa incidence. However, the speed of increase was slower with increasing age. PCa incidence was increased 1.4 times in 2008 compared to that in 2003 or 2013. Regarding cohort effect, the risk of PCa incidence started to increase from 1958 cohort. Conclusion PCa incidence was affected by period of specific year. There was a positive cohort effect on PCa incidence associated with age structural change.

PURPOSE: Radical prostatectomy (RP) is one of main treatments for prostate cancer (Pca). The prevalence of Pca has been decreasing in recent reports. However, no study has reported trends in Pca prevalence or RP rate according to age structural changes. The objective of this study was to investigate trends in Pca prevalence and frequency of RP according to age structural change. MATERIALS AND METHODS: We evaluated trends in Pca prevalence and RP rate using National Health Insurance Data from 2005 to 2015. Relationships for Pca prevalence and RP rate with age structural change were also determined. Primary outcomes included trends in Pca prevalence and RP rates according to age groups, comparing those before and after 2011. RESULTS: Pca prevalence tended to increase before 2011 and decreased after 2011 in persons in the 60-years age group. RP rate increased pattern before 2011 and decreased after 2011 in age groups of 50s, 60s, and over 70s. Pca prevalence and age structural change showed a significantly positive relationship in all age groups, except for the age group under 40 years. RP rate and age structural change also showed a significantly positive relationship in all age groups. CONCLUSION: Age structural change can affect the decreasing trend in Pca prevalence and RP rate in South Korea. Future studies are needed to validate this result.
Humans ; Korea ; National Health Programs ; Passive Cutaneous Anaphylaxis ; Prevalence ; Prostate ; Prostatectomy ; Prostatic Neoplasms

Bronchial provocation tests are of value in the evaluation of airway hyperresponsiveness. Nonspecific bronchial challenge (methacholine, mannitol, exercise, etc.) is used when the symptoms, physical examination, and measurements of pulmonary function are unremarkable in the diagnosis of asthma, when a patient is suspected of having occupational asthma or exercise-induced bronchoconstriction (EIB), and when a screening test for asthma or EIB is required for some occupational groups in whom bronchospasm would pose an unacceptable hazard. Methacholine inhalation challenge is most widely used pharmacologic challenge and highly sensitive. For appropriate interpretation of the results of methacholine provocation, it is important to perform the test with the standardized protocol and to recognize that inhalation methods significantly influence the sensitivity of the procedure. Indirect challenges (e.g., mannitol and exercise) correlate with airway inflammation and are more specific but less sensitive for asthma. Indirect provocation tests are used to confirm asthma, to differentiate asthma from other airway diseases, and to evaluate EIB.
Asthma ; Asthma, Occupational ; Bronchial Provocation Tests ; Bronchial Spasm ; Bronchoconstriction ; Diagnosis ; Exercise Test ; Humans ; Inflammation ; Inhalation ; Mannitol ; Mass Screening ; Methacholine Chloride ; Occupational Groups ; Physical Examination