Validation of the IBD-Control Questionnaire across different sociodemographic and clinical subgroups: secondary analysis of a nationwide electronic survey.

Background: The IBD-Control Questionnaire is a simple, generic measure of patient-perceived disease control used increasingly in clinical practice and research. We aimed to address knowledge gaps in its psychometric performance, to ensure that it can be used with confidence in a variety of contexts.

Methods: We analysed 7341 responses to the IBD Registry COVID-19 survey, sent to 40 911 patients who completed an online self-assessment tool during the pandemic.

CGRP, Amylin, Immunology, and Headache Medicine.

Background: Calcitonin gene-related peptide (CGRP) therapeutics introduce new excitement and possibly yet to be determined distressing discords in the field of Headache Medicine. Growth in knowledge of CGRP in the pathophysiology of migraine introduced CGRP antagonism to headache treatment. Potential adverse effects on the other circulatory and neurovascular diseases have been foremost concerns.

Antigens and Antibodies in Disease With Specifics About CGRP Immunology.

Growth in knowledge about calcitonin gene-related peptide (CGRP) in the pathophysiology of migraine brought CGRP antagonism to headache medicine. Failures in development of small molecule CGRP receptor antagonists and increasing knowledge and use of monoclonal antibodies (mAbs) in medicine led to the breakthrough development of large molecule anti-CGRP mAbs: eptinezumab, erenumab, fremanezumab, and galcanezumab. This specifics about CGRP immunology aims to outline: (1) knowledge needed for CGRP antagonism and (2) developmental issues of specific CGRP antagonists for provider use.

Adenocarcinoma in a Koff Urinary Ileal Diversion.

The use of an ileal conduit as a means of treatment for bladder cancer or dysfunction is widely used and understood. However, long term surveillance of that conduit has not been strongly established and set forth as a means of screening. We present a 76yo female with a history of neurogenic bladder secondary to paraplegia who underwent the formation of a "Koff" pouch as a conduit.

The TGF-β pathway mediates doxorubicin effects on cardiac endothelial cells.

Elevated ALK4/5 ligands including TGF-β and activins have been linked to cardiovascular remodeling and heart failure. Doxorubicin (Dox) is commonly used as a model of cardiomyopathy, a condition that often precedes cardiovascular remodeling and heart failure. In 7-8-week-old C57Bl/6 male mice treated with Dox we found decreased capillary density, increased levels of ALK4/5 ligand and Smad2/3 transcripts, and increased expression of Smad2/3 transcriptional targets.

CDP7657, an anti-CD40L antibody lacking an Fc domain, inhibits CD40L-dependent immune responses without thrombotic complications: an in vivo study.

Introduction: CD40 ligand (CD40L) blockade has demonstrated efficacy in experimental autoimmune models. However, clinical trials of hu5c8, an anti-human CD40L IgG1 antibody, in systemic lupus erythematosus (SLE) were halted due to an increased incidence of thrombotic events. This study evaluated CDP7657, a high affinity PEGylated monovalent Fab' anti-CD40L antibody fragment, to assess whether an Fc-deficient molecule retains efficacy while avoiding the increased risk of thrombotic events observed with hu5c8.

Tobacco, Nicotine, and Headache.

Background: Migraineurs variably attribute the cause of their headache to tobacco exposure, whereas tobacco is often stated to cause headache-related disability worldwide. Given tobacco's physiological and emotional addictiveness and migraine's substantial economic impact, improved functionality can be difficult for those with migraine exposed to tobacco products. Environmental tobacco exposure in indoor spaces and workplaces is associated with exacerbation of headache.

Variable Holocene deformation above a shallow subduction zone extremely close to the trench.

Histories of vertical crustal motions at convergent margins offer fundamental insights into the relationship between interplate slip and permanent deformation. Moreover, past abrupt motions are proxies for potential tsunamigenic earthquakes and benefit hazard assessment. Well-dated records are required to understand the relationship between past earthquakes and Holocene vertical deformation.

ERK-dependent phosphorylation of HSF1 mediates chemotherapeutic resistance to benzimidazole carbamates in colorectal cancer cells.

Drugs containing the benzimidazole carbamate scaffold include anthelmintic and antifungal agents, and they are now also recognized as having potential applications in the treatment of colorectal and other cancers. These agents act by binding to β-tubulin, and in doing so they disrupt microtubules, arrest cell division, and promote apoptotic cell death in malignant cells. We have evaluated several commercially available benzimidazole carbamates for cytotoxic activity in colorectal cancer cells.

Anti-BDCA2 monoclonal antibody inhibits plasmacytoid dendritic cell activation through Fc-dependent and Fc-independent mechanisms.

Type I interferons (IFN-I) are implicated in the pathogenesis of systemic lupus erythematosus (SLE). In SLE, immune complexes bind to the CD32a (FcγRIIa) receptor on the surface of plasmacytoid dendritic cells (pDCs) and stimulate the secretion of IFN-I from pDCs. BDCA2 is a pDC-specific receptor that, when engaged, inhibits the production of IFN-I in human pDCs.

Adenosine 2A receptor agonism: A single intrathecal administration attenuates motor paralysis in experimental autoimmune encephalopathy in rats.

A single intrathecal dose of adenosine 2A receptor (A2AR) agonist was previously reported to produce a multi-week reversal of allodynia in two different models of neuropathic pain in addition to downregulating glial activation markers in the spinal cord. We aimed to determine whether a single intrathecal administration of an A2AR agonist was able to attenuate motor symptoms induced by experimental autoimmune encephalopathy. Two A2AR agonists (CGS21680 and ATL313) significantly attenuated progression of motor symptoms following a single intrathecal administration at the onset of motor symptoms.

Heat shock factor 1 confers resistance to Hsp90 inhibitors through p62/SQSTM1 expression and promotion of autophagic flux.

Heat shock protein 90 (Hsp90) has an important role in many cancers. Biochemical inhibitors of Hsp90 are in advanced clinical development for the treatment of solid and hematological malignancies. At the cellular level, their efficacy is diminished by the fact that Hsp90 inhibition causes activation of heat shock factor 1 (HSF1).

Intrathecal injection of adenosine 2A receptor agonists reversed neuropathic allodynia through protein kinase (PK)A/PKC signaling.

A single intrathecal dose of adenosine 2A receptor (A2AR) agonist was previously reported to produce a multi-week reversal of allodynia in a chronic constriction injury (CCI) model of neuropathic pain. We aimed to determine if this long-term reversal was induced by A2AR agonism versus more generalized across adenosine receptor subtypes, and begin to explore the intracellular signaling cascades involved. In addition, we sought to identify whether the enduring effect could be extended to other models of neuropathic pain.

Episodic migraines in children: limited evidence on preventive pharmacological treatments.

The authors conducted a systematic literature review of preventive pharmacological treatments for episodic childhood migraines searching several databases through May 20, 2012. Episodic migraine prevention was examined in 24 publications of randomized controlled trials that enrolled 1578 children in 16 nonrandomized studies. Single randomized controlled trials provided low-strength evidence that propranolol would result in complete cessation of migraine attacks in 713 per 1000 children treated (95% confidence interval, 452-974); trazodone and nimodipine decreased migraine days, while topiramate, divalproex, and clonidine were no more effective than placebo in preventing migraines.

Preventive pharmacologic treatments for episodic migraine in adults.

Objectives: Systematic review of preventive pharmacologic treatments for community-dwelling adults with episodic migraine.

Data Sources: Electronic databases through May 20, 2012.

Eligibility Criteria: English-language randomized controlled trials (RCTs) of preventive drugs compared to placebo or active treatments examining rates of ≥50 % reduction in monthly migraine frequency or improvement in quality of life.

Systemic administration of an alpha-7 nicotinic acetylcholine agonist reverses neuropathic pain in male Sprague Dawley rats.

Unlabelled: Alpha-7 nicotinic acetylcholine receptor (α7 nAChR) agonists attenuate pain and inflammation in preclinical models. This study tested whether systemic delivery of an α7 nAChR agonist attenuates neuropathic pain and associated immune-mediated pro-inflammation. Hind paw response thresholds to mechanical stimuli in male Sprague Dawley rats were assessed before and after sciatic chronic constriction injury (CCI) or sham surgery.

Prior exposure to repeated morphine potentiates mechanical allodynia induced by peripheral inflammation and neuropathy.

Opioids, such as morphine, induce potent analgesia and are the gold standard for the treatment of acute pain. However, opioids also activate glia, inducing pro-inflammatory cytokine and chemokine production, which counter-regulates the analgesic properties of classical opioid receptor activation. It is not known how long these adverse pro-inflammatory effects last or whether prior morphine could sensitize the central nervous system (CNS) such that responses to a subsequent injury/inflammation would be exacerbated.

Sex and estradiol influence glial pro-inflammatory responses to lipopolysaccharide in rats.

There is a greater prevalence of neuroinflammatory diseases in females than males. Microglia, the major immunocompetent cells of the central nervous system, play a key role in neuroinflammation. We aimed to determine if inherent differences in toll-like receptor 4 mediated pro-inflammatory response in glia could possibly contribute to the skewed female prevalence of neuroinflammatory disorders.

Two separate synchronous primary genitourinary tumors.

A 54-year-old man presented to the office with gross painless hematuria, dysuria, and urinary frequency. He was diagnosed with renal cell carcinoma of the kidney and transitional cell carcinoma of the bladder. The article reviews the presentation, radiology, pathology, and intervention of an uncommon case of synchronous primary carcinomas, and aims to show the importance of continued clinical suspicion for multiple genitourinary primary neoplasms.

Predicting erectile dysfunction following surgical correction of Peyronie's disease without inflatable penile prosthesis placement: vascular assessment and preoperative risk factors.

Introduction: Surgical therapy remains the gold standard treatment for Peyronie's Disease (PD). Surgical options include plication, grafting, and placement of inflatable penile prosthesis (IPP). Postoperative erectile dysfunction (ED) is a potential complication for PD surgery without IPP.