International Neurourology Journal Research Articles

A Discussion Between Past and Present Editor-in-Chief of the International Neurourology Journal: Three Decades of History.

The International Neurourology Journal (Int Neurourol J, INJ) is a quarterly international journal that publishes high-quality research papers that provide the most significant and promising achievements in the fields of clinical neurourology and fundamental science. Specifically, fundamental science includes the most influential research papers from all fields of science and technology, revolutionizing what physicians and researchers practicing the art of neurourology worldwide know. Thus, we welcome valuable basic research articles to introduce cutting-edge translational research of fundamental sciences to clinical neurourology. In the editorials, urologists will present their perspectives on these articles. The original mission statement of the INJ was published on October 12, 1997. INJ provides authors a fast review of their work and makes a decision in an average of 3 to 4 weeks of receiving submissions. If accepted, articles are posted online in fully citable form. Supplementary issues will be published interim to quarterlies, as necessary, to fully allow berth to accept and publish relevant articles. Science Citation Index Expanded (SCIE, Web of Science), Scopus, PubMed, PubMed Central, KoreaMed, KoMCI, WPRIM, WorldWideScience.org, DOI/Crossref, EBSCO, Google Scholar.

Basic Research as the Top Priority for INJ.

This year marks the 20th anniversary of the International Neurourology Journal (INJ). I am truly honored to be working as the fifth Editor-in-Chief of this journal. Those of you who are old enough to remember the original journal written in Korean have seen many changes over the last 7 years. In 2010, the journal’s language was changed from Korean to English and from 2012, the journal was selected to be indexed in Thompson Reuters’ Science Citation Index Expanded accessed via the Web of Science. The journal has also changed in size from a quarterly publication to being published 6 times a year including 2 supplementary issues. In 2010, around 40 articles were published; this has now risen to 78 articles in 2016. The impact factor of the journal continues to rise (1.344 in 2015) due to the hard work and cooperation of a talented group of professionals that includes our editorial board with a range of editorial specialists in all areas of neurourology, a dedicated editorial office staff, credible academic partners, and the busy professionals who volunteer their time as peer reviewers for INJ.

Neurourological Application of Neurogenesis and Inflammation and Pain Mechanisms of Rocuronium Bromide

In the present issue of the International Neurourology Journal, 2 interesting topics were included. One is “Current opinion on the role of neurogenesis in the therapeutic strategies for Alzheimer disease, Parkinson disease, and ischemic stroke; considering neuronal voiding function” [1] and the other is “Rocuronium bromide inhibits inflammation and pain by suppressing nitric oxide production and enhancing prostaglandin E2 synthesis in endothelial cells” [2].

New Horizon for Neurourological Research.

Acquiring basic laboratory techniques is contributory to further elucidate the pathogenesis of various conditions. Development of new diagnostic methods and therapeutic modalities will provide new possibilities in medical treatments. Urological complications should not only be accessed in the perspective of urology, instead, urology related disorders should also be considered in relation with prominent cerebral functions. International Neurourology Journal (INJ) has tried to encompass broader topics of the research articles in view of the roles of brain to the urological disorders. In order to accentuate the role of INJ, we have recruited valuable articles in this issue. Present issue includes following supportive contents to apprehend the urological disorders. Neuroinflammation was suggested as the pathogenic factor inducing various psychiatric disorders by degenerating normal neurons through activation of microglia and up-regulation of pro-inflammatory cytokines. Peripheral immune cells were proposed as the alternative therapeutic strategy for neuro-urological diseases. Variations of apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1) D148E have been proposed as the genetic contribution of bladder cancers, and then the authors suggested that increased secretory activity of APE1/Ref-1 D148E might contribute to the increased APE1/Ref-1 in urine or blood. Main advantages and limitations of 3-dimensional visualization for macromolecules were discussed in this issue to enhance clinical diagnosis. As the new diagnostic technique, Lab-on-a-Chip device was introduced for the rapid molecular diagnoses of pathogens, particularly focusing on the detection of foodborne pathogens. Present issue demonstrated that postnatal treadmill exercise of off-spring ameliorated prenatal stress-induced anxiety symptoms. Treadmill exercise also potentiated the therapeutic effect of transplantation of bone marrow stromal cells on traumatic brain injury. Lastly, the possibility of extracellular matrix was proposed as a new therapeutic modality for tissue damage via spontaneous network formation, as an ideal scaffold. As briefly described above, diverse articles comprising from new experimental skills to novel therapeutic approaches are included in this issue. We would like to acknowledge gratitude to the authors for the valuable articles submitted to the special issue of INJ. The efforts of INJ to identify the urinary disorders in relation with cerebral functions will be continued. These attempts will precipitate to expedite the comprehension and treatment of the urological disorders.

Origin of Urgency Symptom in Underactive Bladder: Commentary on "Underactive Bladder: Clinical Features, Urodynamic Parameters, and Treatment" (Int Neurourol J 2015;19:185-9).

To the editor: In the previous issue of International Neurourology Journal, Nathan Hoag and Johan Gani reported clinical features of underactive bladder (UAB) in their cohort [1]. The most common urinary symptom among identified UAB patients was urgency (63.3%), followed by weak stream (61.0%). Discussing this unexpected finding, the authors only commented that “an appropriate symptom-based definition will prove challenging to describe” for defining UAB. Urinary urgency is definitely the predominant symptom of overactive bladder. Of course, a patient with urgency does not always have overactive bladder. As the authors reported, it is quite possible that a patient with urgency will prove to have UAB in actual practice. The origin of urgency symptoms in UAB patients may be attributed to three possible explanations. The first candidate is definitely concomitant detrusor overactivity. This condition is traditionally termed detrusor hyperreflexia with impaired contractility (DHIC). DHIC seems to be the most probable and attractive explanation for urgency in UAB. However, only 24.1% of patients in the cohort proved to have DHIC, which could not explain all cases. As the next candidate, urinary tract infection (UTI) could be associated with urgency in UAB patients. Recurrent UTI was reported in 25.3% of patients in the cohort, which possibly affected reports of subjective urinary symptoms. Bacteriuria proved to be associated with urinary urgency, especially in elderly women [2]. The last candidate may be deranged bladder sensation, which is often combined with UAB [3]. In patients with diabetes, a sensory deficit precedes bladder motor problems in the development of UAB [4]. These patients often recognize bladder fullness as a vague pressure in the lower abdomen rather than a true initial voiding sensation. With the resulting increased bladder volume, this recognition tends to come too late to allow enough time for actual voiding. The short time interval between first recognition and actual voiding may cause patients to report urgency symptoms. Urgency symptoms in UAB may well occur, and originate from diverse causes including DHIC, UTI, or a sensory deficit. The old axiom that “the bladder is an unreliable witness” seems to be also true in the case of UAB [5]. Differential diagnosis may give us a clue to management. In cases of urgency associated with UTI, antibiotics should be considered first. Anticholinergics may be helpful to decrease urgency with DHIC, but not with a sensory deficit. The clinical implication of UAB subclassification by sensory component warrants further research.

Interleukin-33 as a Potential Therapeutic Target for Interstitial Cystitis: New Perspectives on Mast Cell Regulation.

There are many problems still unresolved by modern medicine. In the field of voiding disorders, interstitial cystitis (IC) remains a representative disease yet to be conquered. The exact pathophysiologic mechanism of IC is not understood. Although several hypotheses have been proposed, including leaky epithelium, mast cell activation, and neurogenic inflammation, no theory has been clearly established yet [1]. IC may have multiple causes and may represent a final common reaction of the bladder to multifactorial etiology. Most researchers believe that the mast cell plays a key role in the common pathophysiology of IC. Despite many efforts to clarify the etiology of IC, our knowledge is insufficient for useful insights into effective treatments [2]. The current therapeutic goal is the improvement of quality of life, and not curative treatment. It is believed that histamine, which is secreted from mast cells, causes specific symptoms of IC such as pain, hyperemia, and fibrosis. Therefore, antihistamine treatment to adjust mast cell activation is considered a scientifically robust and rational therapy for IC. However, results using antihistamines in clinical practice were disappointing. Sufficient evidence does not exist to conclusively state that antihistamines effectively regulate the activation of mast cells in the bladder [3]. In this issue of the International Neurourology Journal, we have published an article reviewing new perspectives on mast cell regulation [4]. It was confirmed in other organs that interleukin (IL) 33 can modulate allergic inflammation. IL-33 is closely related to mast cell activation, which is considered the core of IC pathogenesis. Therefore, it may be possible to regulate mast cell activation by inhibiting IL-33. Promising results have been reported in a number of studies. However, because the reaction of the anti–IL-33 could vary in different organs, we have many challenges to overcome before systemic administration of anti–IL-33 as a therapeutic agent can be implemented. Nevertheless, this is valuable work as it presents a potential therapeutic target for an incurable disease yet unconquered by modern medicine. The most important message of this review for urologists is included in the last sentence of conclusion: “co-operative research among allergologists and urologists could yield more meaningful conclusions about the pathophysiologic mechanism and treatment strategies for interstitial cystitis” [4].

Implantable Bladder Sensors for Long-term Monitoring of Bladder Volume.

Voiding diaries, also called frequency volume charts, are an essential instrument to explore the voiding status of patients with lower urinary tract symptoms (LUTS) and incontinence [1]. Patients record micturition times, voided volume with or without other factors including fluid intake, incontinence, urgency, and urge incontinence over a period of days. This task is associated with patient burden, and increased recording periods decrease patient compliance [2]. Although several electronic voiding diaries have recently been developed and applied to decrease patient burden, the problem persists. Small sensors implanted in the bladder to automatically record pressure and volume and times of voiding may offer a new option for assessment and treatment of LUTS and incontinence. Several studies have described the development of implantable bladder sensors to monitor real-time functional changes [3,4]. In this issue of International Neurourology Journal, Dakurah et al. [5] introduce several types of implantable bladder sensors and discuss specific issues regarding hermeticity, biocompatibility, telemetry, drift, power transfer, and compatibility with medical imaging tools such as computed tomography and magnetic resonance imaging. Although an unmet clinical need might enable medical device development, we clinicians should understand from an engineering viewpoint the possible improvements and emerging trends in the design of implantable bladder sensors that may overcome the current issues [6].

Application of Oncology Research to Resolve a Problem in Neurourology

The urinary bladder is a spherical organ composed of smooth muscle with a unique contractile property. On voiding cystourethrograms usually observed in our clinic, 300–400 mL of fluid in the full bladder completely disappears after voiding. This is possible due to shortening of the outer circumference of the bladder by more than 70%. If the smooth muscle of the bladder wall were to be replaced by skeletal muscle under the same influence of central and peripheral nervous systems, only about 30% length change would be possible, resulting in significant residual urine [1]. This suggests that cellular signaling and regulatory networks in the detrusor muscle greatly influence the change in bladder contractility in several clinically important conditions such as overactive bladder or benign prostatic hyperplasia. However, information on this topic is unclear, and another target having a central role in contractility control will need to be added. A live cell is similar to a rechargeable battery [2]. Energy released from adenosine triphosphate (ATP) or adenosine diphosphate hydrolysis is used to supply energy for cellular processes. The discharging cellular batteries are continuously recharged by catabolism through dynamic feedback mechanisms that monitor intracellular energy levels. Adenosine monophosphate (AMP)-activated protein kinase (AMPK) fulfills this role, and this activity is regulated allosterically by the ratio of AMP and ATP [2,3]. Although it is best known for its role as a key sensor of cellular energy in almost all eukaryotes, AMPK, as shown recently, regulates almost all cellular functions, including cell growth and proliferation, and mitochondrial homeostasis [2,4], and has some interconnections to signaling pathways involved in cancer biology and contractility changes [5,6]. Furthermore, recent discoveries in AMPK research may offer some important insights into neurourology, suggesting a regulatory role of AMPK in detrusor contractility control, similar to its role in the heart [6]. The role of AMPK in the bladder, particularly regarding functional aspects such as contractility control, has not yet been investigated in detail [7], although some progress has been made in bladder cancer research [8,9]. In this issue of International Neurourology Journal, Kim [9] summarizes recent findings on the relationship between AMPK and bladder cancer that will provide basic information necessary for the development of research in contractility change in bladder function.

How far has the international neurourology journal progressed since its transformation into an english language journal?

PurposeThe publisher of the International Neurourology Journal changed the text to English in 2010 to promote the journal as an international publication. Four years later, what has happened to this journal? This paper will use citation indicators to describe the degree of internationalization.MethodsCitation indicators such as impact factors, total citations from Web of Science, Science Journal Rankings (SJR), cites per documents (2 years), and Hirsch indexes (h-indexes) from Web of Science, digital object identifier (DOI)/CrossRef, ScimagoJR, or Scopus were calculated. In addition, the native countries of the authors and researchers citing the journal in Web of Science were analyzed.ResultsImpact factors in 2012 and 2013 were 0.645 and 0.857, respectively. Total citations in 2011, 2012, and 2013 from Web of Science were 15, 51, and 99, respectively, and the SJRs in 2011 and 2012 were 0.220 and 0.390, respectively. The h-indexes from DOI/CrossRef, Scopus, and Web of Science were 7, 8, and 6, respectively. Out of 153 unsolicited published papers, 27 (17.6%) were from outside of Korea. The researchers citing the journal in Web of Science and Scopus were primarily from the United States, Korea, China, the United Kingdom, and France. Funding agencies supported 39 of 101 original articles (38.6%).ConclusionsAfter changing the text to the English language, the citation indicators show that the International Neurourology Journal has been elevated to an international journal. Although the nationality of authors varies from year to year, the increase in the number of manuscripts from international authors is obvious.

Let's Pay Attention to the Average.

Before advancing in every step of development in medicine, researchers may experience a period of agony. However, once that painful step is overcome, progress to the next step is possible. Thanks to such agony, new research products, theories, and technologies are produced, that can be applied in the medical field after undergoing peer-reviews. During these stages of conquest and progress, academic journals play the role of locomotives, carrying new information to intelligent readers. Our journal, the International Neurourology Journal (INJ), has changed its format to mandatory written English, and has attempted to become more globalized over the last 3 years. In the next 3 years, our journal aims to be a forum for discussion and communication between readers and researchers. What should we strive for? First, as researchers, we should not engage in time-consuming competition for acceptance of submitted journal articles. In addition, we should increase the global competitiveness of domestic journals, such as our journal. Competition between domestic researchers in foreign journals is time-consuming, as it uses our material for overseas benefits. In order to improve the quality of our journal, we need to conduct high-level discussions between the majority of members who have average knowledge, and we need to increase international competitiveness through the effort of our editors and staff. In order to make use of excellent related areas, an integrated academic journal should play the role of linking such areas. Following epoch-making medical questions and projects, new technology and successes produced by medical star researchers have always followed. The concept of hygiene, antibiotics, anesthesia, vaccination, the discovery of the structure of DNA, and evidence-based medicine are examples. In the climb to academic excellence, overseas academic journals that have shared groundbreaking medical progress have faced the problem of what to do after reaching the summit. In general, most journals return to their average standard after reaching the top. However, some journals chose to differentiate themselves from their previous level, by choosing selected pieces of work that move the journal in the editors' desired direction. These efforts make their journals distinct, and enable the journals to perform the role of leading and guiding researchers. What will the future be like? Our journal will fuse work that is unfamiliar to the majority of average researchers with peer-review evaluation, in order to create new knowledge. In the age of information, those who create knowledge rule society. Therefore, the gap between information poor and rich readers will increase. However, medical opinions and results should not be monopolized by a selected few. The stages of growth of a journal are in the following order: accumulation of funds to establish an on-line submission system, unification of language into English, and invitation of high quality journal articles that can increase the citation index. After that, the journal should attain an increase in the Science Citation Index (SCI) ranking. The INJ is the only one of its kind in Asia that specializes in this particular field. The 2013 impact factor shows that the journal improved itself by 85% is acknowledgeable. In addition, the research-funded thesis and dissertation numbers are high, and such trends show that the number of foreigners contributing to the journal is on the rise. In this issue [1], to have an opportunity to look back on some of our work, we have replaced the review article with an original article from our collection of special issues. In our fields of study, many of our colleagues and readers are acknowledging that having a unique style of manuscripts published in our journal is increasingly important. It is now imperative that we make advancements, not solely by using the SCI citation index alone, but through other channels as well. Our journal is at this point of progress. In order to gain global competition for submission, we editors should ponder over how to accurately evaluate submitted manuscripts in order to achieve this goal.

International neurourology journal: get ready for the readers' quest.

Solving the mystery of the bladder involves both basic and clinical research, much of it utilizing rapidly advancing modern technologies and theories. The best form of clinical research is always built upon a solid foundation of cutting-edge basic research; our journal aims to apply knowledge and discovery gained from the basic science to medical practice in a timely and efficient way. Our journal accepts basic researches not only in urology but also from immunology, rheumatology, cardiology, and other fields that can help solve the mystery of the bladder. Basic science across a wide range of clinical fields have a tendency toward compartmentalization, resulting in limited or delayed access for clinicians to potentially translatable watershed developments in science and technology. Thus, we welcome valuable basic research articles outside the scope of urology, thereby introducing the result to urology as soon as possible. In the editorials, urologists will present their perspectives on these articles [1,2]. Recently, the International Neurourology Journal was selected for coverage in the Thomson Reuters products: Science Citation Index Expanded, online at the Web of Science. Our journal will be processed electronically for the coverage, starting from the first issue of volume 16, 2012. We are ready to foster the solutions to unraveling the secrets of the bladder, tailored to the new format of translational research, based on the effective and unbiased international communication.

Neurourology transforms the drug development experience.

Continuous efforts are being made to develop new drugs or dietary supplements from natural products. These efforts are important in improving the outcomes of many intractable diseases. In an article published in this issue of the International Neurourology Journal, the antiapoptotic effect of berberine against ischemic brain injury in gerbils has been reported [1]. The authors suggest that this antiapoptotic effect might be mediated through the inhibition of reactive astrogliosis and microglia activation. Berberine is a type of isoquinoline alkaloid extracted from the root of Coptis japonica, the bark of Phellodendron amurense, and the root of Berberis vulgaris. Currently, the major clinical indications of berberine include bacterial diarrhea, intestinal parasite infections, and ocular trachoma infections. The diverse effects of berberine on tumors, diabetes mellitus, cardiovascular deregulation, immunology disorders, and neurodegenerative diseases have been studied [2,3,4,5]. Berberine has been shown to suppress the growth of bladder cancer and has been proposed as a novel chemotherapeutic agent [6]. Pretreatment with berberine elicited a protective effect against hypoxia/reoxygenation-induced apoptosis in human renal proximal tubular cells [7]. Berberine was suggested as a possible agent to improve neurogenic bladder in diabetic rats as well [8]. The effects of berberine on urological disorders have also been reported. Functional studies on the diverse mechanisms of berberine will be helpful for the treatment of stroke-associated neurourological diseases.

How to make the most of big data in the era of complexity.

In this issue of International Neurourology Journal, we have a review article of 'Big Data Analysis Using Modern Statistical and Machine Learning Methods in Medicine' [1]. The primary objective of this article is to examine clinical data, gene-gene and gene-environment interactions using statistical approaches. The paper is divided into clinical data, gene expression data, single nucleotide polymorphism (SNP) data, and epigenetic data, and it concludes with the basics of Bayesian networks (BNs). Typically, clinical data is analyzed using either linear or logistic regressions. Linear regression is a statistical method for modeling the relationship between a dependent variable and one or more explanatory variables while logistic regression is widely used in outcome variables that has two outcomes. Nowadays, these clinical data has been extended to include genomic and environmental data. Recent genome studies have discovered significant associations between complex diseases and SNPs. In conjunction with clinical data, SNP-SNP interactions play role in understanding the development of complex diseases. Algorithms that use different search mechanisms, different ranking criterion, and/or that are geared toward specific situations have been developed. One of the modern statistical models that enable us to combine these clinical, genomic, and environmental data, is BN. BN is a directed acyclic graph in which each node represents a variable and each arc represents a relationship. In BN, each arc is interpreted as a direct influence between a parent node and a child node. BN have basic sub-networks, i.e., converging, diverging, and serial, that provide ways to express causal interactions in more intuitive ways. BN model has been widely used to learn predictive models from data. BNs can model causality based on researcher's knowledge, data or both. It is also feasible to use two or more of the previous models in order to reduce errors while obtaining better results. With ever growing data in medicine, we should be also aware of recent trend in statistical analyses to get better understanding of such data. In return we will obtain more comprehensive knowledge on pathophysiology and better idea on how to establish treatment strategies of complex diseases.

The Measurement of Intra-abdominal Pressure in Awake Rat Cystometry

The history of animal cystometry revolves around the desire for specification of the lower urinary tract functions as a dynamic reservoir. However, in animal models, the functional significance of intra-abdominal pressure (IAP) in urodynamics have not been well-studied. The measurement of IAP and its interpretation are essential for evaluating the bladder functions. In addition, the IAP is a key physiological parameter in an animal experimental model of voiding dysfunction. In this issue of International Neurourology Journal, Lee and Yoon [1] provides an overview of the significance of the IAP in an awake-animal cystometry. There are two key roles of the IAP in an awake-animal cystometry model as shown below:

Desiring the Painless Urodynamic Study

Advances in technology and gains in modern medicine are intertwined. Development of medicine through comprehensive application of advanced technology is a principal condition for their mutual progress. However, they also serve as an important limiting factor to each other. The clearly established need for improved medicine cannot be satisfied by the limitation in technology. For example, current urodynamic study is limited by catheterization for measuring bladder-related pressures [1], although urologists consider it indispensable. If a future technique to measure pressures with advanced images alone were available without direct connection to the bladder space, the urodynamic study would be considerably more successful as a diagnostic procedure for voiding dysfunction. However, since such a technique is lacking now, an implantable medical device is needed for this study as an intermediate technique between present and future techniques. Research in this area has already begun [2]; however, more sophistication is needed in the future. Biomedical engineering can be defined as the comprehensive and advanced application of engineering principles and design concepts based on the clinician’s need for healthcare improvement. The medical doctor is a practical user, and can more ac curately predict the outcomes of using the newly developed medical device for the human body. However, the doctor’s need should be realistic given the abilities of the current technology. Therefore, the exact situation for using a specific technique should be determined. In this issue of International Neurourology Journal, Joung [3] explains the status of development of implantable medical devices from the viewpoint of an engineer.

Lab-on-a-chip for Urology

In an effort to make a diagnosis of diseases, to assess the treatment outcomes and to evaluate the prognosis, many investigators are currently dedicating themselves to identifying disease markers more easily through a minimally-invasive method using human samples. This has eventually improved the results of critical analysis of individual steps of the various methods. Nevertheless, much scientific attention has been focused on the methodology rather than on the development of devices. Still, samples or specimens are prepared in a test tube or a petri dish although they can be processed in large volumes irrespective of the technique. With the exceptions of some biomarkers and micromanipulation, there are no technological advancements leading to the widespread use in the field of urology. However, more so than changes in a procedure or methodology as technical advancements have had a great effect on the clinical application. In this issue of International Neurourology Journal, Lee [1] introduces the concept of the technology, which is based on the microfluidic system. As the state-of-the-art technology, the Lab-on-a-chip is based on the miniaturization of laboratory apparatus, and it is a technology that has been gaining increasing interest. It is not just a methodology, and it focuses on the development of technology. In other words, it aims to construct a totally-integrated, disposable microfluidic system that is operated by a single mode. Moreover, it generates pressure that can be applied on-site with an enhanced portability and disposability and that can be operated more simply and rapidly for making medical, surgical and clinical diagnoses. Compared with the application of the lab-on-a-chip in other clinical specialties, the application of this technology in the field of urology remains unnoticeable, although it is presumed to be applicable for diagnosing urinary tract infection or for performing in vitro fertilization [2,3]. Of course, it is evident that there are many obstacles in integrating and making a clinical application of it. It would therefore be mandatory to develop reliable methods for directing flow through a network of channels. In the field of neurourology, uro-oncology, and nephrology, urine is treated as valuable human samples. Many investigators have great interest in identifying disease makers with the use of human urine samples and in enabling the clinical application of such methods. To date, however, no studies have reported the successful results. This leads to the speculation that we would achieve great things if we make an effort to understand the current state-of-the-art system and then to apply it to the diagnosis of urologic diseases. Thus, it will be established as a novel innovative technology. Keeping pace with the current trends, the review article of this issue will provide a high-level understanding of micro- and nanotechnologies, novel research areas that are making a rapid progress.

Future Challenges in Nocturia: Relevance to Voiding Clock?

Sleep is a naturally stereotypical behavioral state, characterized by reduced or absent consciousness and inactivity of all voluntary muscles. However, sleeping is not just an inactive state, but an essential activity for survival, such as for the repair and renewing of our bodies. The timing of the sleep cycle is controlled by a complex interaction between the circadian clock and a separate sleep-wake homeostatic process. This complex interaction is also affected by the aging process [1]. Even though the precise functions and mechanisms of sleep are only partially understood, recent evidence suggests that the primary mammalian circadian timing system, which is located in the suprachiasmatic nucleus (SCN) of the hypothalamus, resets itself every day in response to light signals. The SCN receives information from the eye and transfers it to the pineal gland, the endocrine gland that secrets melatonin, the hormone of darkness. Recent studies have found that melatonin has beneficial effects for the treatment of certain sleep disorders. Besides the SCN master clock, independent circadian clocks are also found in many organs, such as the esophagus, lung, liver, pancreas, spleen, thymus, skin, and kidney, which constitute the so-called peripheral oscillators [2,3]. The presence of a bladder clock and influence by a kidney clock remain to be elucidated. Nocturia is a common storage symptom with a significantly negative impact on health-related quality of life in aging people [4]. Because the average age of people in developed countries is increasing, it is expected that nocturia will become more common in the future, because the prevalence of nocturia increases with age. Although substantial efforts have been made to provide insights into the etiology of the disease and corresponding remedial actions, many unanswered questions remain about the bladder in terms of sleep. The article by Cho et al. [5] in this issue of the journal will be recognized as a valuable landmark that lays the foundation for future research to shed some light on the circadian control of voiding function and dysfunction via the molecular clockwork. Through the International Neurourology Journal, we also hope to foster and reinforce the dialogue between basic researchers and health care providers.

Learning From Heart Failure: How Will We Lead Bladder Failure Into the Future?

Bladder failure is a condition or a collection of symptoms in which the bladder is unable to evacuate the urine completely due to inadequate detrusor contraction [1]. This hidden condition that does not usually lead to complaints is common in the elderly, and its incidence increases inevitably with aging. Moreover, there is a lack of basic research into the underlying causes of this disease, along with a lack of unified terminology and related definitions and acceptable diagnostic criteria. The biggest burden to us, clinicians, is the necessity of requiring incapable elderly patients to perform painful clean intermittent catheterization several times a day. It is urgent that we restart by coming to a consensus on the terminology of this disease. In cases of heart failure, there seems to be no other currently used terminology for that condition, which might be the first important step towards the current achievements in treating heart failure. This may be the key to the possible differences in the academic content and achievements in the fields of heart failure and bladder failure. The term “bladder failure” still remains surrounded by ambiguity with a lack of accepted terminology [2]. In our opinion, the terminology for any disease should be simple and easily recognizable by the patients as well as physicians. Although “bladder failure” may give the impression of an all-or-nothing event, giving the condition a name may be the first step toward an expansion in the development of bladder failure research. The heart and bladder are harder-working organs than any others in the body, continuously pumping blood or urine out. The failure of these organs may have similar underlying mechanistic causes and pathogenesis. In this issue of International Neurourology Journal, Marquez et al. [3] introduces a close relationship between the heart and mitochondrial function in the regulation of cellular energetics and metabolism, and describes the beneficial effect of targeting mitochondrial biogenesis in failing hearts. Furthermore, although there are currently no pharmacologic agents that directly affect mitochondrial biogenesis in heart failure, this article shows current advances in the development of heart failure therapies, including mitochondrial biogenesis, mitochondrial oxidative stress, and mitochondrial pore transition proteins. A similar relationship between the bladder and mitochondrial function was described previously in a study of bladder failure [4,5]. However, researchers in the field of bladder failure seem to have much work to do in the future.