Peripheral Mechanisms Underlying Bacillus Calmette-Guerin-Induced Lower Urinary Tract Symptoms (LUTS).

Non-muscle invasive bladder cancer (NMIBC) accounts for approximately 70-75% of all bladder cancer cases. The standard treatment for high-risk NMIBC involves transurethral tumour resection followed by intravesical Bacillus Calmette-Guerin (BCG) immunotherapy. While BCG immunotherapy is both safe and effective, it frequently leads to the development of lower urinary tract symptoms (LUTS) such as urinary urgency, frequency, dysuria, and pelvic discomfort.

BCG induced lower urinary tract symptoms during treatment for NMIBC-Mechanisms and management strategies.

Non-muscle invasive bladder cancer (NMIBC) accounts for ~70-75% of total bladder cancer tumors and requires effective early intervention to avert progression. The cornerstone of high-risk NMIBC treatment involves trans-urethral resection of the tumor followed by intravesical Bacillus Calmette-Guerin (BCG) immunotherapy. However, BCG therapy is commonly accompanied by significant lower urinary tract symptoms (LUTS) including urinary urgency, urinary frequency, dysuria, and pelvic pain which can undermine treatment adherence and clinical outcomes.

Beyond the urothelium: Interplay between autonomic nervous system and bladder inflammation in urinary tract infection, bladder pain syndrome with interstitial cystitis and neurogenic lower urinary tract dysfunction in spinal cord injury-ICI-RS 2023.

Introduction: Inflammation and neuronal hypersensitivity are reactive protective mechanisms after urothelial injury. In lower urinary tract dysfunctions (LUTD), such as urinary tract infection (UTI), bladder pain syndrome with interstitial cystitis (BPS/IC) and neurogenic LUTD after spinal cord injury (SCI), chronic inflammation can develop. It is unclear how the protective reactionary inflammation escalates into chronic disease in some patients.

Animal models of interstitial cystitis/bladder pain syndrome.

Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS) is a chronic disorder characterized by pelvic and/or bladder pain, along with lower urinary tract symptoms that have a significant impact on an individual's quality of life. The diverse range of symptoms and underlying causes in IC/BPS patients pose a significant challenge for effective disease management and the development of new and effective treatments. To facilitate the development of innovative therapies for IC/BPS, numerous preclinical animal models have been developed, each focusing on distinct pathophysiological components such as localized urothelial permeability or inflammation, psychological stress, autoimmunity, and central sensitization.

Post-hepatectomy liver failure: A timeline centered review.

Background: Post-hepatectomy liver failure (PHLF) is a leading cause of postoperative mortality after liver surgery. Due to its significant impact, it is imperative to understand the risk stratification and preventative strategies for PHLF. The main objective of this review is to highlight the role of these strategies in a timeline centered way around curative resection.

An ordered, self-assembled nanocomposite with efficient electronic and ionic transport.

Mixed conductors-materials that can efficiently conduct both ionic and electronic species-are an important class of functional solids. Here we demonstrate an organic nanocomposite that spontaneously forms when mixing an organic semiconductor with an ionic liquid and exhibits efficient room-temperature mixed conduction. We use a polymer known to form a semicrystalline microstructure to template ion intercalation into the side-chain domains of the crystallites, which leaves electronic transport pathways intact.

The diverse functions of the DEG/ENaC family: linking genetic and physiological insights.

The DEG/ENaC family of ion channels was defined based on the sequence similarity between degenerins (DEG) from the nematode Caenorhabditis elegans and subunits of the mammalian epithelial sodium channel (ENaC), and also includes a diverse array of non-voltage-gated cation channels from across animal phyla, including the mammalian acid-sensing ion channels (ASICs) and Drosophila pickpockets. ENaCs and ASICs have wide ranging medical importance; for example, ENaCs play an important role in respiratory and renal function, and ASICs in ischaemia and inflammatory pain, as well as being implicated in memory and learning. Electrophysiological approaches, both in vitro and in vivo, have played an essential role in establishing the physiological properties of this diverse family, identifying an array of modulators and implicating them in an extensive range of cellular functions, including mechanosensation, acid sensation and synaptic modulation.

The T-type calcium channel Ca V 3.2 regulates bladder afferent responses to mechanical stimuli.

The bladder wall is innervated by a complex network of afferent nerves that detect bladder stretch during filling. Sensory signals, generated in response to distension, are relayed to the spinal cord and brain to evoke physiological and painful sensations and regulate urine storage and voiding. Hyperexcitability of these sensory pathways is a key component in the development of chronic bladder hypersensitivity disorders including interstitial cystitis/bladder pain syndrome and overactive bladder syndrome.

Cloud-based fusion imaging improves operative metrics during fenestrated endovascular aneurysm repair.

Objective: Endovascular treatment of complex aortic pathology has been associated with increases in procedural-related metrics, including the operative time and radiation exposure. Three-dimensional fusion imaging technology has decreased the radiation dose and iodinated contrast use during endovascular aneurysm repair. The aim of the present study was to report our institutional experience with the use of a cloud-based fusion imaging platform during fenestrated endovascular aneurysm repair (FEVAR).

Urinary Tract Infection in Overactive Bladder: An Update on Pathophysiological Mechanisms.

Overactive bladder (OAB) is a clinical syndrome defined by urinary urgency, increased daytime urinary frequency and/or nocturia, with or without urinary incontinence, that affects approximately 11% of the western population. OAB is accepted as an idiopathic disorder, and is charactersied clinically in the absence of other organic diseases, including urinary tract infection. Despite this, a growing body of research provides evidence that a significant proportion of OAB patients have active bladder infection.

TGR5 agonists induce peripheral and central hypersensitivity to bladder distension.

The mechanisms underlying chronic bladder conditions such as interstitial cystitis/bladder pain syndrome (IC/BPS) and overactive bladder syndrome (OAB) are incompletely understood. However, targeting specific receptors mediating neuronal sensitivity to specific stimuli is an emerging treatment strategy. Recently, irritant-sensing receptors including the bile acid receptor TGR5, have been identified within the viscera and are thought to play a key role in neuronal hypersensitivity.

A syngeneic inoculation mouse model of endometriosis that develops multiple comorbid visceral and cutaneous pain like behaviours.

Endometriosis is a chronic and debilitating condition, commonly characterised by chronic pelvic pain (CPP) and infertility. Chronic pelvic pain can be experienced across multiple pelvic organs, with comorbidities commonly effecting the bowel, bladder, and vagina. Despite research efforts into endometriosis pathophysiology, little is known about how endometriosis induces CPP, and as such, therapeutic interventions are lacking.

Guanylate cyclase-C agonists as peripherally acting treatments of chronic visceral pain.

Irritable bowel syndrome (IBS) is a chronic gastrointestinal disorder characterized by abdominal pain and altered bowel habit that affects ~11% of the global population. Over the past decade, preclinical and clinical studies have revealed a variety of novel mechanisms relating to the visceral analgesic effects of guanylate cyclase-C (GC-C) agonists. Here we discuss the mechanisms by which GC-C agonists target the GC-C/cyclic guanosine-3',5'-monophosphate (cGMP) pathway, resulting in visceral analgesia as well as clinically relevant relief of abdominal pain and other sensations in IBS patients.

The value of liquid biopsy in the diagnosis and staging of hepatocellular carcinoma: a systematic review.

Background: Blood-borne tumour markers in the form of circulating tumour cells (CTCs) are of intense research interest in the diagnostic and prognostic work-up of hepatocellular carcinoma (HCC).

Methods: This is a meta-analysis. Using a PICO strategy, adults with HCC was the population, with the individual CTCs as the intervention and comparators.

A mouse model of endometriosis that displays vaginal, colon, cutaneous, and bladder sensory comorbidities.

Endometriosis is a painful inflammatory disorder affecting ~10% of women of reproductive age. Although chronic pelvic pain (CPP) remains the main symptom of endometriosis patients, adequate treatments for CPP are lacking. Animal models that recapitulate the features and symptoms experienced by women with endometriosis are essential for investigating the etiology of endometriosis, as well as developing new treatments.

Activation of MrgprA3 and MrgprC11 on Bladder-Innervating Afferents Induces Peripheral and Central Hypersensitivity to Bladder Distension.

Understanding the sensory mechanisms innervating the bladder is paramount to developing efficacious treatments for chronic bladder hypersensitivity conditions. The contribution of Mas-gene-related G protein-coupled receptors (Mrgpr) to bladder signaling is currently unknown. Using male and female mice, we show with single-cell RT-PCR that subpopulations of DRG neurons innervating the mouse bladder express (14%) and (38%), either individually or in combination, with high levels of coexpression with (81%-89%).

Incidence of allergen-specific and total immunoglobulin E positivity in children undergoing adenotonsillectomy.

Aim: To conduct a prospective, consecutive cohort study to evaluate the incidence of allergen-specific and total immunoglobulin E (IgE) in a paediatric population undergoing adenotonsillectomy for sleep-disordered breathing.

Methods: A total of 64 consecutive patients presenting for adenotonsillectomy at a single centre were recruited over a period of 3 months. All patients underwent adenotonsillectomy and had allergen-specific and total IgE serum testing at the time of anaesthesia induction.

Characterisation of soil micro-topography using a depth camera.

Soil surface roughness controls how water ponds on and flows over soil surfaces. It is a crucial parameter for erosion and runoff studies. Surface roughness has traditionally been measured using manual techniques that are simple but laborious.

Experimentally Induced Bladder Permeability Evokes Bladder Afferent Hypersensitivity in the Absence of Inflammation.

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic urological condition characterised by urinary urgency, frequency and pelvic pain, that significantly impacts the quality of life for ∼5% of women. Bladder sensation is coordinated by primary afferent sensory neurons that innervate the bladder wall, translating bladder stretch into signals that travel to the brain via the spinal cord. Whilst the pathophysiology of IC/BPS remains unknown, an increase in the permeability of the bladder urothelium has been proposed as an initiating cause.

Identification of a Quorum Sensing-Dependent Communication Pathway Mediating Bacteria-Gut-Brain Cross Talk.

Despite recently established contributions of the intestinal microbiome to human health and disease, our understanding of bacteria-host communication pathways with regard to the gut-brain axis remains limited. Here we provide evidence that intestinal neurons are able to "sense" bacteria independently of the host immune system. Using supernatants from cultures of the opportunistic pathogen (.

Pain in Endometriosis.

Endometriosis is a chronic and debilitating condition affecting ∼10% of women. Endometriosis is characterized by infertility and chronic pelvic pain, yet treatment options remain limited. In many respects this is related to an underlying lack of knowledge of the etiology and mechanisms contributing to endometriosis-induced pain.

A spider-venom peptide with multitarget activity on sodium and calcium channels alleviates chronic visceral pain in a model of irritable bowel syndrome.

Chronic pain is a serious debilitating condition that affects ∼20% of the world's population. Currently available drugs fail to produce effective pain relief in many patients and have dose-limiting side effects. Several voltage-gated sodium (NaV) and calcium (CaV) channels are implicated in the etiology of chronic pain, particularly NaV1.

Pharmacological modulation of voltage-gated sodium (NaV) channels alters nociception arising from the female reproductive tract.

Dyspareunia, also known as vaginal hyperalgesia, is a prevalent and debilitating symptom of gynaecological disorders such as endometriosis and vulvodynia. Despite this, the sensory pathways transmitting nociceptive information from female reproductive organs remain poorly characterised. As such, the development of specific treatments for pain associated with dyspareunia is currently lacking.