The <em>MUC2 </em>Gene Product: Polymerisation and Post-Secretory Organisation—Current Models

\ua9 2024 by the authors.MUC2 mucin, the primary gel-forming component of intestinal mucus, is well researched and a model of polymerisation and post-secretory organisation has been published previously. Recently, several significant developments have been made which either introduce new ideas or challenge previous theories. New ideas include an overhaul of the MUC2 C-terminal globular structure which is proposed to harbour several previously unobserved domains, and include a site for an extra intermolecular disulphide bridge dimer between the cysteine 4379 of adjacent MUC2 C-termini. MUC2 polymers are also now thought to be secreted attached to the epithelial surface of goblet cells in the small intestine and removed following secretion via a metalloprotease meprin β-mediated cleavage of the von Willebrand D2 domain of the N-terminus. It remains unclear whether MUC2 forms intermolecular dimers, trimers, or both, at the N-termini during polymerisation, with several articles supporting either trimer or dimer formation. The presence of a firm inner mucus layer in the small intestine is similarly unclear. Considering this recent research, this review proposes an update to the previous model of MUC2 polymerisation and secretion, considers conflicting theories and data, and highlights the importance of this research to the understanding of MUC2 mucus layers in health and disease

Otologic opioid usage and pain control in the postoperative period

Introduction: Patients’ unused prescription opioids can be diverted and increase the overall opioid burden on society. Therefore, otolaryngologists can reduce opioid influx by minimizing excess tablets in opioid prescriptions. We hypothesize that otology patients at TJUH receive more opioid tablets than needed to effectively manage postoperative pain. Methods: Patients ages ≥18 years old who received otologic surgery at TJUH were included in this prospective observational study between November 2019 and August 2020. Patients were provided a survey for recording pain on postoperative days 0, 1, 3, and 7 and the amount of remaining opioids from their prescription. Opioid amounts were converted to morphine milligram equivalents (MME) for analysis. Mean and standard deviation were calculated for pain scores, MME prescribed, and MME used. A multivariate regression model was used to predict increased MME usage for selected indicators. Results: Ninety-one patients completed the study. Collectively, forty-seven percent of MME were unused, while seventy percent of MME were unused in patients receiving a transcanal incision (n=28/91). Pain scores and MME utilization differed significantly between transcanal and postauricular cohorts (p=0.002). Additionally, patients with a postauricular incision had 60% more opioid usage (p\u3c0.001). Low pain scores and high proportions of unused MME in stapedectomy and transcanal tympanoplasty indicate that postoperative pain in these procedures may be managed with reduced opioid prescriptions and/or NSAIDs. Discussion: A significant amount of opioids were unused in this study. Patients with postauricular incisions had significantly increased opioid utilization than patients with transcanal incisions. These results support the hypothesis that otologic patients are overprescribed postoperative opioids. Otologists may be able to manage postoperative pain with reduced opioid prescriptions, multimodal analgesia, and increased patient education. This can be leveraged as a point of intervention in the opioid epidemic to reduce excess opioids in the community

Plastid evolution: gene transfer and the maintenance of 'stolen' organelles

Many heterotrophic organisms sequester plastids from prey algae and temporarily utilize their photosynthetic capacity. A recent article in BMC Genomics reveals that the dinoflagellate Dinophysis acuminata has acquired photosynthesis-related genes by horizontal gene transfer, which might explain its ability to retain 'stolen' plastids for extended periods of time

Association between proton pump inhibitor therapy and clostridium difficile infection: a contemporary systematic review and meta-analysis.

Abstract Introduction Emerging epidemiological evidence suggests that proton pump inhibitor (PPI) acid-suppression therapy is associated with an increased risk of Clostridium difficile infection (CDI). Methods Ovid MEDLINE, EMBASE, ISI Web of Science, and Scopus were searched from 1990 to January 2012 for analytical studies that reported an adjusted effect estimate of the association between PPI use and CDI. We performed random-effect meta-analyses. We used the GRADE framework to interpret the findings. Results We identified 47 eligible citations (37 case-control and 14 cohort studies) with corresponding 51 effect estimates. The pooled OR was 1.65, 95% CI (1.47, 1.85), I2 = 89.9%, with evidence of publication bias suggested by a contour funnel plot. A novel regression based method was used to adjust for publication bias and resulted in an adjusted pooled OR of 1.51 (95% CI, 1.26–1.83). In a speculative analysis that assumes that this association is based on causality, and based on published baseline CDI incidence, the risk of CDI would be very low in the general population taking PPIs with an estimated NNH of 3925 at 1 year. Conclusions In this rigorously conducted systemic review and meta-analysis, we found very low quality evidence (GRADE class) for an association between PPI use and CDI that does not support a cause-effect relationship

Variants in Hormone Biosynthesis Genes and Risk of Endometrial Cancer.

We investigated the risk associated with variants in three genes involved in estrogen biosynthesis, CYP11A1, CYP17A1, and CYP19A1, in the population-based case-control study of Estrogen, Diet, Genetics, and Endometrial Cancer. This study was conducted in New Jersey in 2001-2006 with 417 cases and 402 controls. For CYP11A1, there was no association between the number of [TTTTA]( n ) repeats (D15S520) and risk. For CYP17A1, risk was somewhat lower among women with the C/C genotype at T-34C (rs743572) (adjusted OR = 0.65, 95% CI 0.41-1.02). For CYP19A1, risk was lower among women homozygous for the 3-bp deletion (rs11575899) in exon 4 (adjusted OR = 0.44, 95% CI 0.26-0.76), while the number of [TTTA]( n ) repeats was not significantly related to risk: the adjusted OR for n = 7/7 repeats versus n \u3e 7/\u3e7 repeats was 0.81 (95% CI 0.54-1.23). In stratified analyses, results for CYP19A1 were stronger among women with higher (\u3e or =27.4) body mass index: for the homozygous deletion, OR = 0.30 (95% CI 0.15-0.62); for the n = 7/7 genotype, OR = 0.49 (95% CI 0.26-0.93). The interaction between the n = 7/7 genotype and BMI was statistically significant (p = 0.01). The insertion/deletion variant in CYP19A1 appears to be related to risk of endometrial cancer; risk associated with variants in this gene may vary according to BMI

Early response to antibiotic treatment in European patients hospitalized with complicated skin and soft tissue infections: analysis of the REACH study

Background: The treatment of complicated skin and soft tissue infections (cSSTI) is challenging and many patients do not receive adequate first-line therapy. REACH (REtrospective Study to Assess the Clinical Management of Patients With Moderate-to-Severe cSSTI or Community-Acquired Pneumonia in the Hospital Setting) was a retrospective observational study of cSSTI patients in real-life settings in European hospitals. In this analysis, we review characteristics and outcomes of patients with an early response (<= 72 hours) compared with those without an early response to treatment. We also compare the results according to two differing definitions of early response, one of which (Definition 1) requires resolution of fever within 72 hours, in line with previous US FDA guidelines. Methods: Patients were adults hospitalized with cSSTIs 2010-2011 and requiring treatment with intravenous antibiotics. Clinical management, clinical outcomes and healthcare resource use were assessed using a descriptive analysis approach. Results: The analysis set included 600 patients, of which 363 showed early response with Definition 1 and 417 with Definition 2. Initial treatment modification was frequent, and highest in patients without early response (48.1% with Definition 1). Patients without early response were more likely to have diabetes than those with early response (31.6% vs. 22.9%,respectively) and to suffer from more severe disease (e.g. skin necrosis: 14.8% and 7.7%,respectively), to be infected with difficult-to-treat microorganisms and to have recurrent infections. Furthermore, patients without early response had a higher rate of adverse clinical outcomes (e.g. septic shock) and higher use of healthcare resources. The results obtained with the two definitions for early response were largely similar. Conclusions: This study highlights the significance of early evaluation of patients in hospitals, in potentially preventing prolonged use of inappropriate or ineffective antibacterial therapy

Women's experiences of ovulation testing: A qualitative analysis

© 2015 Jones et al.Background: The introduction of home digital ovulation tests (OTs) has provided a simple solution for women wishing to optimise the timing of intercourse when trying to conceive. However, despite this, very little is understood about women's experiences of using these tests. Methods: We carried out qualitative, semi-structured telephone interviews with women who were seeking to conceive (not actively undergoing clinical investigation/fertility treatment) from the general UK population. The interviews were conducted following participation in a randomised controlled trial (RCT) in which participants were either provided with digital home OTs to assist in timing intercourse (n = 18) or advised to have intercourse every 2-3 days (n = 18). The interviews were digitally recorded, transcribed and then analysed using Framework analysis to identify the themes. Results: Data saturation was reached after 36 interviews. The use of the OT appeared to elicit 10 key themes, which could be described within the context of three overarching issues: 1) a positive impact (understanding the menstrual cycle, confirming when ovulating, emotional support, improving the relationship), 2) a negative impact (changing sex life and relationship with their partner, the emotional consequences of prolonged use, questions and uncertainty about what their results mean for them) and 3) the experiences of trying to conceive in general (use of clinical guidance and emotional experience). Conclusions: Overall, the use of home OTs were found to affect women's thoughts and feelings in multiple ways during attempts to conceive. Although some women reported a range of negative experiences when using OTs, they also reported similar negative experiences when trying to conceive without using the tests. However, there were many positive themes associated with OT use, including an increased understanding of the menstrual cycle, confirmation of ovulation timing and providing a source of help and support when trying to conceive. Overall, when women are trying to conceive, ensuring they have access to high-quality information, including use of OT, may be of benefit to help address some of the questions and uncertainties that were raised by the participants in this study. Trial registration number: NCT01084304