Same-day discharge for pediatric Nuss procedure; an analysis of the NSQIP-pediatric database from 2017-2022.

Purpose: Limited data exists evaluating same-day discharge for pediatric Nuss procedure; most being single-center studies. Our analysis, using the NSQIP-P registry, aimed to assess if same-day discharge for the Nuss procedure influenced post-operative outcomes.

Methods: The NSQIP-P database (2017-2022) identified patients who underwent the Nuss procedure.

Trends and outcomes in pediatric laparoscopic appendectomy: a NSQIP-P analysis of same-day discharge and readmission rates.

Purpose: Practice patterns of same-day discharge for pediatric laparoscopic appendectomy for non-perforated appendicitis are not well-analyzed. Our aim is to evaluate current practice patterns and outcomes of same-day discharge for these patients.

Methods: NSQIP-P retrospective registry identified patients (2017-2021) who underwent laparoscopic appendectomy for non-perforated appendicitis.

Oxytocin Analogues for the Oral Treatment of Abdominal Pain.

Abdominal pain presents an onerous reality for millions of people affected by gastrointestinal disorders such as irritable bowel syndrome (IBS) and inflammatory bowel diseases (IBD). The oxytocin receptor (OTR) has emerged as a new analgesic drug target with OTR expression upregulated on colon-innervating nociceptors in chronic visceral hypersensitivity states, accessible via luminal delivery. However, the low gastrointestinal stability of OTR's endogenous peptide ligand oxytocin (OT) is a bottleneck for therapeutic development.

Operative Timing for Elective Thoracoscopic Lobectomy for CPAM and Sequestration: A NSQIP-Pediatric Analysis 2017-2021.

Background: There is limited literature on optimal timing for elective thoracoscopic lobectomy for congenital pulmonary airway malformations (CPAM) and sequestration. Using NSQIP-P, we aim to assess optimal operative timing for elective thoracoscopic lobectomy for CPAM and sequestration.

Methods: Data from the NSQIP-Pediatric registry was used to evaluate elective thoracoscopic lobectomy patients from 2017 to 2021 diagnosed with congenital pulmonary airway malformation or sequestration.

Same-Day Discharge for Elective Pediatric Laparoscopic Gastrostomy Tube Insertion is Safe and Increasing in Frequency; A NSQIP Pediatric Retrospective Review 2017 to 2021.

Background: There is limited literature reviewing same-day discharge for elective pediatric gastrostomy tube placement. Our aim was to assess the outcomes and national trends of same-day discharge following elective pediatric laparoscopic gastrostomy.

Methods: ACS NSQIP-P registry data from 2017 to 2021 was used to evaluate elective pediatric laparoscopic gastrostomy patients who presented from home and discharged home with a diagnosis of failure to thrive, feeding difficulty or dysphagia.

Sequence-specific targeting of intrinsically disordered protein regions.

A general approach to design proteins that bind tightly and specifically to intrinsically disordered regions (IDRs) of proteins and flexible peptides would have wide application in biological research, therapeutics, and diagnosis. However, the lack of defined structures and the high variability in sequence and conformational preferences has complicated such efforts. We sought to develop a method combining biophysical principles with deep learning to readily generate binders for any disordered sequence.

Crypt and Villus Enterochromaffin Cells are Distinct Stress Sensors in the Gut.

The crypt-villus structure of the small intestine serves as an essential protective barrier, with its integrity monitored by the gut's sensory system. Enterochromaffin (EC) cells, which are rare sensory epithelial cells that release serotonin (5-HT), surveil the mucosal environment and signal both within and outside the gut. However, it remains unclear whether EC cells in intestinal crypts and villi respond to different stimuli and elicit distinct responses.

Comparative localization of colorectal sensory afferent central projections in the mouse spinal cord dorsal horn and caudal medulla dorsal vagal complex.

The distal colon and rectum (colorectum) are innervated by spinal and vagal afferent pathways. The central circuits into which vagal and spinal afferents relay colorectal nociceptive information remain to be comparatively assessed. To address this, regional colorectal retrograde tracing and colorectal distension (CRD)-evoked neuronal activation were used to compare the circuits within the dorsal vagal complex (DVC) and dorsal horn (thoracolumbar [TL] and lumbosacral [LS] spinal levels) into which vagal and spinal colorectal afferents project.

Validation for Abbreviated Hospital Stay in Pediatric Patients with Solid Organ Injury.

Background: In 2000, the American Pediatric Surgical Association (APSA) published guidelines for the management of pediatric solid organ injury, recommending a hospital length of stay (LOS) of grade of injury plus 1 day. Since the publication of these guidelines, several studies have suggested that it is safe to discharge patients sooner based upon hemodynamic and clinical factors. The results of several of these studies have been confounded by the existence of other injuries.

Peripheral and central neuroplasticity in a mouse model of endometriosis.

Chronic pelvic pain (CPP) is the most debilitating symptom of gynaecological disorders such as endometriosis. However, it remains unclear how sensory neurons from pelvic organs affected by endometriosis, such as the female reproductive tract, detect and transmit nociceptive events and how these signals are processed within the central nervous system (CNS). Using a previously characterized mouse model of endometriosis, we investigated whether the increased pain sensitivity occurring in endometriosis could be attributed to (i) changes in mechanosensory properties of sensory afferents innervating the reproductive tract, (ii) alterations in sensory input from reproductive organs to the spinal cord or (iii) neuroinflammation and sensitization of spinal neural circuits.

Gut enterochromaffin cells drive visceral pain and anxiety.

Gastrointestinal (GI) discomfort is a hallmark of most gut disorders and represents an important component of chronic visceral pain. For the growing population afflicted by irritable bowel syndrome, GI hypersensitivity and pain persist long after tissue injury has resolved. Irritable bowel syndrome also exhibits a strong sex bias, afflicting women three times more than men.

The voltage-gated sodium channel Na1.7 underlies endometriosis-associated chronic pelvic pain.

Chronic pelvic pain (CPP) is the primary symptom of endometriosis patients, but adequate treatments are lacking. Modulation of ion channels expressed by sensory nerves innervating the viscera has shown promise for the treatment of irritable bowel syndrome and overactive bladder. However, similar approaches for endometriosis-associated CPP remain underdeveloped.

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.

Targeting the endocannabinoid system for the treatment of abdominal pain in irritable bowel syndrome.

The management of visceral pain in patients with disorders of gut-brain interaction, notably irritable bowel syndrome, presents a considerable clinical challenge, with few available treatment options. Patients are increasingly using cannabis and cannabinoids to control abdominal pain. Cannabis acts on receptors of the endocannabinoid system, an endogenous system of lipid mediators that regulates gastrointestinal function and pain processing pathways in health and disease.

Disengaging spinal afferent nerve communication with the brain in live mice.

Our understanding of how abdominal organs (like the gut) communicate with the brain, via sensory nerves, has been limited by a lack of techniques to selectively activate or inhibit populations of spinal primary afferent neurons within dorsal root ganglia (DRG), of live animals. We report a survival surgery technique in mice, where select DRG are surgically removed (unilaterally or bilaterally), without interfering with other sensory or motor nerves. Using this approach, pain responses evoked by rectal distension were abolished by bilateral lumbosacral L5-S1 DRG removal, but not thoracolumbar T13-L1 DRG removal.

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.

Clodronate Treatment Prevents Vaginal Hypersensitivity in a Mouse Model of Vestibulodynia.

Introduction: Improved understanding of vestibulodynia pathophysiology is required to develop appropriately targeted treatments. Established features include vulvovaginal hyperinnervation, increased nociceptive signalling and hypersensitivity. Emerging evidence indicates macrophage-neuron signalling contributes to chronic pain pathophysiology.

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.

Orai1- and Orai2-, but not Orai3-mediated I is regulated by intracellular pH.

Three Orai (Orai1, Orai2, and Orai3) and two stromal interaction molecule (STIM1 and STIM2) mammalian protein homologues constitute major components of the store-operated Ca entry mechanism. When co-expressed with STIM1, Orai1, Orai2 and Orai3 form highly selective Ca channels with properties of Ca release-activated Ca (CRAC) channels. Despite the high level of homology between Orai proteins, CRAC channels formed by different Orai isoforms have distinctive properties, particularly with regards to Ca -dependent inactivation, inhibition/potentiation by 2-aminoethyl diphenylborinate and sensitivity to reactive oxygen species.

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.

Shine a light: Under-ice light and its ecological implications in a changing Arctic Ocean.

The Arctic marine ecosystem is shaped by the seasonality of the solar cycle, spanning from 24-h light at the sea surface in summer to 24-h darkness in winter. The amount of light available for under-ice ecosystems is the result of different physical and biological processes that affect its path through atmosphere, snow, sea ice and water. In this article, we review the present state of knowledge of the abiotic (clouds, sea ice, snow, suspended matter) and biotic (sea ice algae and phytoplankton) controls on the underwater light field.

Pharmacological Inhibition of the Voltage-Gated Sodium Channel Na1.7 Alleviates Chronic Visceral Pain in a Rodent Model of Irritable Bowel Syndrome.

The human nociceptor-specific voltage-gated sodium channel 1.7 (hNa1.7) is critical for sensing various types of somatic pain, but it appears not to play a primary role in acute visceral pain.

Design of a Stable Cyclic Peptide Analgesic Derived from Sunflower Seeds that Targets the κ-Opioid Receptor for the Treatment of Chronic Abdominal Pain.

The rising opioid crisis has become a worldwide societal and public health burden, resulting from the abuse of prescription opioids. Targeting the κ-opioid receptor (KOR) in the periphery has emerged as a powerful approach to develop novel pain medications without central side effects. Inspired by the traditional use of sunflower () preparations for analgesic purposes, we developed novel stabilized KOR ligands (termed as helianorphins) by incorporating different dynorphin A sequence fragments into a cyclic sunflower peptide scaffold.

Pruritogenic mechanisms and gut sensation: putting the "irritant" into irritable bowel syndrome.

Chronic abdominal pain is a common clinical condition experienced by patients with irritable bowel syndrome (IBS). A general lack of suitable treatment options for the management of visceral pain is the major contributing factor to the debilitating nature of the disease. Understanding the underlying causes of chronic visceral pain is pivotal to identifying new effective therapies for IBS.

Olorinab (APD371), a peripherally acting, highly selective, full agonist of the cannabinoid receptor 2, reduces colitis-induced acute and chronic visceral hypersensitivity in rodents.

Abdominal pain is a key symptom of inflammatory bowel disease and irritable bowel syndrome, for which there are inadequate therapeutic options. We tested whether olorinab-a highly selective, full agonist of the cannabinoid receptor 2 (CB2)-reduced visceral hypersensitivity in models of colitis and chronic visceral hypersensitivity (CVH). In rodents, colitis was induced by intrarectal administration of nitrobenzene sulfonic acid derivatives.