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The inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), are chronic inflammatory disorders of the intestine. The prevalence in the United States is greater than 200 cases per 100,000, with the total number of IBD patients between 1 and 1.5 million. CD may affect all parts of the gastrointestinal tract, from mouth to anus, but most commonly involves the distal part of the small intestine or ileum, and colon. UC results in colonic inflammation that can affect the rectum only, or can progress proximally to involve part of or the entire colon. Clinical symptoms include diarrhea, abdominal pain, gastrointestinal bleeding, and weight loss. A serious long-term complication of chronic inflammation is the development of colorectal cancer. A genetic basis for IBD had long been recognized based on the increased familial risk. However, significant discordance for CD in twins, and a much less robust phenotypic concordance for UC, suggested additional factors play a role in disease pathogenesis, including environmental factors. In the past several years, progress in understanding the molecular basis of IBD has accelerated, beginning with the generation of animal models of colitis and progressing to the identification of specific genetic markers from candidate gene, gene linkage, and genome-wide association analyses. Genetic studies have also resulted in the recognition of the importance of environmental factors, particularly the crucial role of the gut microbiota in CD and UC. Altered immune responses to the normal intestinal flora are key factors in IBD pathogenesis. In this research topic, the genetic basis of IBD, the genetic and cellular alterations associated with colitis-associated colon cancer, and the emerging role of the intestinal microbiota and other environmental factors will be reviewed.

Background Neuromyelitis optica (NMO), an autoimmune inflammatory disease of the central nervous system, is often associated with retinal abnormalities including thinning of the retinal nerve fiber layer and microcystic changes. Here, we demonstrate that passive transfer of an anti-aquaporin-4 autoantibody (AQP4-IgG) produces primary retinal pathology. Methods AQP4-IgG was delivered to adult rat retinas by intravitreal injection. Rat retinas and retinal explant cultures were assessed by immunofluorescence. Results Immunofluorescence showed AQP4-IgG deposition on retinal Müller cells, with greatly reduced AQP4 expression and increased glial fibrillary acidic protein by 5 days. There was mild retinal inflammation with microglial activation but little leukocyte infiltration and loss of retinal ganglion cells by 30 days with thinning of the ganglion cell complex. Interestingly, the loss of AQP4 was complement independent as seen in cobra venom factor-treated rats and in normal rats administered a mutated AQP4-IgG lacking complement effector function. Exposure of ex vivo retinal cultures to AQP4-IgG produced a marked reduction in AQP4 expression by 24 h, which was largely prevented by inhibitors of endocytosis or lysosomal acidification. Conclusions Passive transfer of AQP4-IgG results in primary, complement-independent retinal pathology, which might contribute to retinal abnormalities seen in NMO patients.

Background Retinal optical coherence tomography (OCT) is a clinical and research tool in multiple sclerosis, where it has shown significant retinal nerve fiber (RNFL) and ganglion cell (RGC) layer thinning, while postmortem studies have reported RGC loss. Although retinal pathology in experimental autoimmune encephalomyelitis (EAE) has been described, comparative OCT studies among EAE models are scarce. Furthermore, the best practices for the implementation of OCT in the EAE lab, especially with afoveate animals like rodents, remain undefined. We aimed to describe the dynamics of retinal injury in different mouse EAE models and outline the optimal experimental conditions, scan protocols, and analysis methods, comparing these to histology to confirm the pathological underpinnings. Methods Using spectral-domain OCT, we analyzed the test-retest and the inter-rater reliability of volume, peripapillary, and combined horizontal and vertical line scans. We then monitored the thickness of the retinal layers in different EAE models: in wild-type (WT) C57Bl/6J mice immunized with myelin oligodendrocyte glycoprotein peptide (MOG 35–55 ) or with bovine myelin basic protein (MBP), in TCR 2D2 mice immunized with MOG 35–55 , and in SJL/J mice immunized with myelin proteolipid lipoprotein (PLP 139–151 ). Strain-matched control mice were sham-immunized. RGC density was counted on retinal flatmounts at the end of each experiment. Results Volume scans centered on the optic disc showed the best reliability. Retinal changes during EAE were localized in the inner retinal layers (IRLs, the combination of the RNFL and the ganglion cell plus the inner plexiform layers). In WT, MOG 35–55 EAE, progressive thinning of IRL started rapidly after EAE onset, with 1/3 of total loss occurring during the initial 2 months. IRL thinning was associated with the degree of RGC loss and the severity of EAE. Sham-immunized SJL/J mice showed progressive IRL atrophy, which was accentuated in PLP-immunized mice. MOG 35–55 -immunized TCR 2D2 mice showed severe EAE and retinal thinning. MBP immunization led to very mild disease without significant retinopathy. Conclusions Retinal neuroaxonal damage develops quickly during EAE. Changes in retinal thickness mirror neuronal loss and clinical severity. Monitoring of the IRL thickness after immunization against MOG 35–55 in C57Bl/6J mice seems the most convenient model to study retinal neurodegeneration in EAE.

Introduction Ectopic sinonasal teeth are uncommon. The classic approach to removal of such foreign bodies was the Caldwell-Luc. In recent years however, endoscopic approaches have become increasingly utilized. Despite this, there is a dearth of literature and consensus regarding the endoscopic removal of ectopic sinonasal teeth. As such, we conducted a systematic review on all cases of endoscopic removal of ectopic sinonasal teeth in the literature. With an understanding of the literature, clinical and technical decision making for patients with this pathology may be elucidated. Methods Systematic review of the Ovid Medline, EMBASE Classic and Pubmed databases were conducted using PRISMA guidelines. Results Our search identified 100 articles. Final inclusion consisted of 23 studies with a total of 27 patient cases. The majority of the patients included were male (70.4%) with a mean age of 27.06 years. Patients presented with a multitude of symptoms, with nasal obstruction (48.14%), rhinorrhea (22.2%), facial pain (22.2%) and epistaxis (22.2%) being most common. Surgeons mostly reported using a 0° endoscope (22.2%) and performing a maxillary antrostomy/uncinectomy (37%) and simple extraction under general anesthetic (41%). Conclusions This systematic review analyzed important epidemiological, clinical and technical information regarding patients with endoscopic removal of sinonasal ectopic teeth. Further research is needed to promote implementation of such data into clinical practice.

Aquaporin-4 (AQP4)-specific T cells are expanded in neuromyelitis optica (NMO) patients and exhibit Th17 polarization. However, their pathogenic role in CNS autoimmune inflammatory disease is unclear. Although multiple AQP4 T-cell epitopes have been identified in WT C57BL/6 mice, we observed that neither immunization with those determinants nor transfer of donor T cells targeting them caused CNS autoimmune disease in recipient mice. In contrast, robust proliferation was observed following immunization of AQP4-deficient (AQP4−/−) mice with AQP4 peptide (p) 135–153 or p201–220, peptides predicted to contain I-Ab–restricted T-cell epitopes but not identified in WT mice. In comparison with WT mice, AQP4−/− mice used unique T-cell receptor repertoires for recognition of these two AQP4 epitopes. Donor T cells specific for either determinant from AQP4−/−, but not WT, mice induced paralysis in recipient WT and B-cell–deficient mice. AQP4-specific Th17-polarized cells induced more severe disease than Th1-polarized cells. Clinical signs were associated with opticospinal infiltrates of T cells and monocytes. Fluorescent-labeled donor T cells were detected in CNS lesions. Visual system involvement was evident by changes in optical coherence tomography. Fine mapping of AQP4 p201–220 and p135–153 epitopes identified peptides within p201–220 but not p135–153, which induced clinical disease in 40% of WT mice by direct immunization. Our results provide a foundation to evaluate how AQP4-specific T cells contribute to AQP4-targeted CNS autoimmunity (ATCA) and suggest that pathogenic AQP4-specific T-cell responses are normally restrained by central tolerance, which may be relevant to understanding development of AQP4-reactive T cells in NMO.

Background Although optic neuritis (ON) is a defining feature of neuromyelitis optica (NMO), appropriate animal models of NMO ON are lacking. Most NMO patients are seropositive for immunoglobulin G autoantibodies (NMO-IgG) against the astrocyte water channel aquaporin-4 (AQP4). Methods Several approaches were tested to develop a robust, passive-transfer mouse model of NMO ON, including NMO-IgG and complement delivery by: (i) retrobulbar infusion; (ii) intravitreal injection; (iii) a single intracranial injection near the optic chiasm; and (iv) 3-days continuous intracranial infusion near the optic chiasm. Results Little ON or retinal pathology was seen using approaches (i) to (iii) . Using approach (iv), however, optic nerves showed characteristic NMO pathology, with loss of AQP4 and glial fibrillary acidic protein immunoreactivity, granulocyte and macrophage infiltration, deposition of activated complement, demyelination and axonal injury. Even more extensive pathology was created in mice lacking complement inhibitor protein CD59, or using a genetically modified NMO-IgG with enhanced complement effector function, including significant loss of retinal ganglion cells. In control studies, optic nerve pathology was absent in treated AQP4-deficient mice, or in wild-type mice receiving control (non-NMO) IgG and complement. Conclusion Passive transfer of NMO-IgG and complement by continuous infusion near the optic chiasm in mice is sufficient to produce ON with characteristic NMO pathology. The mouse model of NMO ON should be useful in further studies of NMO pathogenesis mechanisms and therapeutics.

Levin discusses the right to a jury trial and a remedy for assembly-line justice. The right to trial by jury was enshrined in the Magna Carta, where it was described as \"the principal bulwark of our liberties.\" Of course, America's founders memorialized it in the Sixth Amendment, which has analogs in all state constitutions. Yet today, trial by jury is a rarity, with fewer than 3 percent of federal criminal cases ending in jury trial, and similar data in states. The problem is that growing evidence suggests many of the pleas are instead a function of the outsized leverage prosecutors exert in our justice system. Fortunately, there are many changes in policies and practices that can help mitigate the trial penalty without bringing to a halt the wheels of justice that are so copiously greased by plea bargaining.

Objective Noise in operating rooms (OR) can have negative effects on both patients and surgical care workers. Noise can also impact surgical performance, team communication, and patient outcomes. Such implications of noise have been studied in orthopedics, neurosurgery, and urology. High noise levels have also been demonstrated in Otolaryngology-Head and Neck Surgery (OHNS) procedures. Despite this, no previous study has amalgamated the data on noise across all OHNS ORs to determine how much noise is present during OHNS surgeries. This study aims to review all the literature on noise associated with OHNS ORs and procedures. Methods Ovid Medline, EMBASE Classic, Pubmed, SCOPUS and Cochrane databases were searched following PRISMA guidelines. Data was collected on noise measurement location and surgery type. Descriptive results and statistical analysis were completed using Stata. Results This search identified 2914 articles. Final inclusion consisted of 22 studies. The majority of articles analyzed noise level exposures during mastoid surgery (18/22, 82%). The maximum noise level across all OHNS ORs and OHNS cadaver studies were 95.5 a-weighted decibels (dBA) and 106.6 c-weighted decibels (dBC), respectively ( P  = 0.2068). The mean noise level across all studies was significantly higher in OHNS cadaver labs (96.9 dBA) compared to OHNS ORs (70.1 dBA) ( P  = 0.0038). When analyzed together, the mean noise levels were 84.9 dBA. Conclusions This systematic review demonstrates that noise exposure in OHNS surgery exceeds safety thresholds. Further research is needed to understand how noise may affect team communication, surgical performance and patient outcomes in OHNS ORs. Graphical abstract

Objective Patients are increasingly turning to the Internet as a source of healthcare information. Given that neck dissection is a common procedure within the field of Otolaryngology ‐ Head and Neck Surgery, the aim of this study was to evaluate the quality and readability of online patient education materials on neck dissection. Methods A Google search was performed using the term “neck dissection.” The first 10 pages of a Google search using the term “neck dissection” were analyzed. The DISCERN instrument was used to assess quality of information. Readability was calculated using the Flesch‐Reading Ease, Flesch‐Kincaid Grade Level, Gunning‐Fog Index, Coleman‐Liau Index, and Simple Measure of Gobbledygook Index. Results Thirty‐one online patient education materials were included. Fifty‐five percent (n = 17) of results originated from academic institutions or hospitals. The mean Flesch‐Reading Ease score was 61.2 ± 11.9. Fifty‐two percent (n = 16) of patient education materials had Flesch‐Reading Ease scores above the recommended score of 65. The average reading grade level was 10.5 ± 2.1. The average total DISCERN score was 43.6 ± 10.1. Only 26% of patient education materials (PEMs) had DISCERN scores corresponding to a “good quality” rating. There was a significant positive correlation between DISCERN scores and both Flesch‐Reading Ease scores and average reading grade level. Conclusions The majority of patient education materials were written above the recommended sixth‐grade reading level and the quality of online information pertaining to neck dissections was found to be suboptimal. This research highlights the need for patient education materials regarding neck dissection that are high quality and easily understandable by patients.

Background Head and neck cancer during pregnancy is uncommon. Specifically, laryngeal cancer in pregnancy has only been previously reported 10 times. HPV p16+ supraglottic cancer during pregnancy has never been described in the literature prior to this case report. This case is important to report to understand the most effective and safe diagnostic, treatment and follow-up options available for pregnant patients with laryngeal cancer. Case presentation This report describes a case of a 33-year-old patient who was 24 weeks pregnant presenting with dysphonia and odynophagia. After laryngeal biopsy and MRI she was diagnosed with T3N1M0, stage three p16+ squamous cell carcinoma of the supraglottis. After inter-disciplinary consultation as well as extensive patient discussion, an awake tracheostomy, PEG tube placement and then elective C-section at 28 weeks’ gestation was completed. This was followed by chemoradiotherapy. The patient has remained free from disease with a healthy child at four years post-treatment. Conclusion Supraglottic cancer during pregnancy is rare with only four previous cases reported in the literature. This case report elucidates the importance of including multiple specialities as well as patient preference in the decision-making process regarding treatment for patients with supraglottic cancer during pregnancy. Furthermore, diagnostic and treatment guidelines for pregnant patients with head and neck cancers should be established to promote the best possible oncological, obstetrical and neonatal care.