A Bayesian Method for Exposure Prevalence Comparison During Foodborne Disease Outbreak Investigations.

CDC and health departments investigate foodborne disease outbreaks to identify a source. To generate and test hypotheses about vehicles, investigators typically compare exposure prevalence among case-patients with the general population using a one-sample binomial test. We propose a Bayesian alternative that also accounts for uncertainty in the estimate of exposure prevalence in the reference population. We compared exposure prevalence in a 2020 outbreak of Escherichia coli O157:H7 illnesses linked to leafy greens with 2018-2019 FoodNet Population Survey estimates. We ran prospective simulations using our Bayesian approach at three time points during the investigation. The posterior probability that leafy green consumption prevalence was higher than the general population prevalence increased as additional case-patients were interviewed. Probabilities were >0.70 for multiple leafy green items 2 weeks before the exact binomial p-value was statistically significant. A Bayesian approach to assessing exposure prevalence among cases could be superior to the one-sample binomial test typically used during foodborne outbreak investigations.

Modified Alar Base Reduction: A Novel Technique.

BACKGROUND: Alar base reduction (ABR) surgery is one of the rhinoplasty techniques used to reduce alar flaring, nasal base width, or both. It is crucial for rhinoplasty surgeons to understand and analyze the type of nasal base deformity to achieve satisfactory results and avoid complications. OBJECTIVES: The objective of this study is to describe a novel technique of ABR that addresses alar flaring while avoiding violation of the nostril marginal rim. METHODS: This prospective cohort study included patients with alar flaring who underwent rhinoplasty or septorhinoplasty with ABR using our modified technique. Demographic data, clinical history, aesthetic concerns, and preoperative and postoperative photographs were collected for each patient. The surgical outcome was assessed using subjective scar evaluation scores at 3 and 6 months, the Stony Brook Scar Evaluation Scale at 6 months, and an overall appearance satisfaction score. RESULTS: A total of 8 patients were included in the study. Subjectively, the majority of patients (75%) reported satisfactory scar appearance at the 6-month follow-up. The mean Stony Brook score was 4.7 (SD=0.74). Nostril symmetry was achieved in all patients. Seventy-five percent of the participants expressed satisfaction with the overall appearance. CONCLUSIONS: Our modified ABR technique demonstrates promising results in correcting alar flaring while achieving nostril symmetry with an acceptable scar. Further studies with a larger sample size are needed to evaluate the feasibility of the technique and compare it to other classical techniques. LEVEL OF EVIDENCE: Level IV.

Description of Novel Technique for Managing Insufficient Nasal Skin Volume.

A short nose is a common esthetic problem faced by facial plastic surgeons. Rhinoplasty of the short nose has been recognized as a complex procedure to perform for achieving satisfactory results. The authors presented 4 cases of short nose in 4 Saudi men who underwent rhinoplasty using septal extension graft and closure the skin with secondary intention as an option to control skin tension after graft placement and to increase nose skin volume to prevent skin retraction, which may occur postoperatively during the healing process. Furthermore, the authors have also discussed the surgical outcomes of these 4 cases and overall satisfaction. Finally, the authors reviewed the literature to identify published papers on correcting the short nose technique.

The role of protected areas co-management in enhancing resistance and resilience of deciduous forest ecosystem to extreme climatic events in Bangladesh.

Due to ongoing and projected climate change as well as increasing anthropogenic disturbances, the tropical deciduous forest has been experiencing a decline in its biomass and productivity. To mitigate this adverse effect, many tropical countries have adopted forest co-management engaging local communities. However, the effects of co-management on the resistance and resilience of forest ecosystems to extreme climatic events have rarely been tested. The present study investigates the effects of co-management on resistance and resilience to extreme climatic events in two major tropical deciduous forest protected areas of Bangladesh, namely Madhupur National Park (MNP) and Bhawal National Park (BNP), through remotely sensed satellite data. We used the Google Earth Engine platform to access the Landsat images from 1990 to 2020 for a comprehensive assessment of the forest cover condition under two major management regimes (i.e., traditional and co-management). We find that co-management slows down the rate of forest destruction, where the rate of forest destruction was 108 ha year-1 in MNP and 121 ha year-1 in BNP during the year 1990-2008 under traditional forest management system. Under the co-management regime, forest cover increased by 19 ha year-1 and 41 ha year-1 from 2009 to 2020 respectively in MNP and BNP. Our study finds a highly significant correlation between rainfall (p < 0.001) and forest health, although co-management had poor impacts on forest resistance and resilience in case of extreme climatic events, such as drought and heavy rainfall. We find, no significant impacts of co-management on resistance and resilience to drought in MNP, and on resistance and resilience to heavy rainfall in MNP and BNP. In BNP, the impacts of co-management on resistance (p < 0.05) and resilience (p < 0.01) of forest to drought were highly significant. Forest co-management although have the potentials to reduce the deforestation rate by mitigating anthropogenic disturbances, its capacity to tackle the adverse impact of climate change was limited in our study. An adaptive co-management model, therefore, is crucial for mainstreaming the adverse effect of climate change on the tropical deciduous forest to harness the maximum potential of community participation in forest resources management.

Universal Hepatitis B Vaccination in Adults Aged 19-59 Years: Updated Recommendations of the Advisory Committee on Immunization Practices - United States, 2022.

Hepatitis B (HepB) vaccines have demonstrated safety, immunogenicity, and efficacy during the past 4 decades (1,2). However, vaccination coverage among adults has been suboptimal, limiting further reduction in hepatitis B virus (HBV) infections in the United States. This Advisory Committee on Immunization Practices (ACIP) recommendation expands the indicated age range for universal HepB vaccination to now include adults aged 19-59 years. Removing the risk factor assessment previously recommended to determine vaccine eligibility in this adult age group (2) could increase vaccination coverage and decrease hepatitis B cases.

Fertilized graminoids intensify negative drought effects on grassland productivity.

Droughts can strongly affect grassland productivity and biodiversity, but responses differ widely. Nutrient availability may be a critical factor explaining this variation, but is often ignored in analyses of drought responses. Here, we used a standardized nutrient addition experiment covering 10 European grasslands to test if full-factorial nitrogen, phosphorus, and potassium addition affected plant community responses to inter-annual variation in drought stress and to the extreme summer drought of 2018 in Europe. We found that nutrient addition amplified detrimental drought effects on community aboveground biomass production. Drought effects also differed between functional groups, with a negative effect on graminoid but not forb biomass production. Our results imply that eutrophication in grasslands, which promotes dominance of drought-sensitive graminoids over forbs, amplifies detrimental drought effects. In terms of climate change adaptation, agricultural management would benefit from taking into account differential drought impacts on fertilized versus unfertilized grasslands, which differ in ecosystem services they provide to society.

Invader presence disrupts the stabilizing effect of species richness in plant community recovery after drought.

Higher biodiversity can stabilize the productivity and functioning of grassland communities when subjected to extreme climatic events. The positive biodiversity-stability relationship emerges via increased resistance and/or recovery to these events. However, invader presence might disrupt this diversity-stability relationship by altering biotic interactions. Investigating such disruptions is important given that invasion by non-native species and extreme climatic events are expected to increase in the future due to anthropogenic pressure. Here we present one of the first multisite invader × biodiversity × drought manipulation experiment to examine combined effects of biodiversity and invasion on drought resistance and recovery at three semi-natural grassland sites across Europe. The stability of biomass production to an extreme drought manipulation (100% rainfall reduction; BE: 88 days, BG: 85 days, DE: 76 days) was quantified in field mesocosms with a richness gradient of 1, 3, and 6 species and three invasion treatments (no invader, Lupinus polyphyllus, Senecio inaequidens). Our results suggest that biodiversity stabilized community productivity by increasing the ability of native species to recover from extreme drought events. However, invader presence turned the positive and stabilizing effects of diversity on native species recovery into a neutral relationship. This effect was independent of the two invader's own capacity to recover from an extreme drought event. In summary, we found that invader presence may disrupt how native community interactions lead to stability of ecosystems in response to extreme climatic events. Consequently, the interaction of three global change drivers, climate extremes, diversity decline, and invasive species, may exacerbate their effects on ecosystem functioning.

Mechanism of pulmonary immunosuppression: extrapulmonary burn injury suppresses bacterial endotoxin-induced pulmonary neutrophil recruitment and neutrophil extracellular trap (NET) formation.

Pulmonary immunosuppression often occurs after burn injury (BI). However, the reasons for BI-induced pulmonary immunosuppression are not clearly understood. Neutrophil recruitment and neutrophil extracellular trap (NET) formation (NETosis) are important components of a robust pulmonary immune response, and we hypothesized that pulmonary inflammation and NETosis are defective after BI. To test this hypothesis, we established a mouse model with intranasal LPS instillation in the presence or absence of BI (15% of body surface burn) and determined the degree of immune cell infiltration, NETosis, and the cytokine levels in the airways and blood on d 2. Presence of LPS recruited monocytes and large numbers of neutrophils to the airways and induced NETosis (citrullinated histone H3, DNA, myeloperoxidase). By contrast, BI significantly reduced LPS-mediated leukocyte recruitment and NETosis. This BI-induced immunosuppression is attributable to the reduction of chemokine (C-C motif) ligand (CCL) 2 (monocyte chemoattractant protein 1) and CCL3 (macrophage inflammatory protein 1α). BI also suppressed LPS-induced increase in IL-17A, IL-17C, and IL-17E/IL-25 levels in the airways. Therefore, BI-mediated reduction in leukocyte recruitment and NETosis in the lungs are attributable to these cytokines. Regulating the levels of some of these key cytokines represents a potential therapeutic option for mitigating BI-mediated pulmonary immunosuppression.-Sakuma, M., Khan, M. A. S., Yasuhara, S., Martyn, J. A., Palaniyar, N. Mechanism of pulmonary immunosuppression: extrapulmonary burn injury suppresses bacterial endotoxin-induced pulmonary neutrophil recruitment and neutrophil extracellular trap (NET) formation.

Mortgage Discrimination and Racial/Ethnic Concentration Are Associated with Same-Race/Ethnicity Partnering among People Who Inject Drugs in 19 US Cities.

Racial/ethnic homophily in sexual partnerships (partners share the same race/ethnicity) has been associated with racial/ethnic disparities in HIV. Structural racism may partly determine racial/ethnic homophily in sexual partnerships. This study estimated associations of racial/ethnic concentration and mortgage discrimination against Black and Latino residents with racial/ethnic homophily in sexual partnerships among 7847 people who inject drugs (PWID) recruited from 19 US cities to participate in CDC's National HIV Behavioral Surveillance. Racial/ethnic concentration was defined by two measures that respectively compared ZIP code-level concentrations of Black residents to White residents and Latino residents to White residents, using the Index of Concentration at the Extremes. Mortgage discrimination was defined by two measures that respectively compared county-level mortgage loan denial among Black applicants to White applicants and mortgage loan denial among Latino applicants to White applicants, with similar characteristics (e.g., income, loan amount). Multilevel logistic regression models were used to estimate associations. Interactions of race/ethnicity with measures of racial/ethnic concentration and mortgage discrimination were added to the final multivariable model and decomposed into race/ethnicity-specific estimates. In the final multivariable model, among Black PWID, living in ZIP codes with higher concentrations of Black vs. White residents and counties with higher mortgage discrimination against Black residents was associated with higher odds of homophily. Living in counties with higher mortgage discrimination against Latino residents was associated with lower odds of homophily among Black PWID. Among Latino PWID, living in ZIP codes with higher concentrations of Latino vs. White residents and counties with higher mortgage discrimination against Latino residents was associated with higher odds of homophily. Living in counties with higher mortgage discrimination against Black residents was associated with lower odds of homophily among Latino PWID. Among White PWID, living in ZIP codes with higher concentrations of Black or Latino residents vs. White residents was associated with lower odds of homophily, but living in counties with higher mortgage discrimination against Black residents was associated with higher odds of homophily. Racial/ethnic segregation may partly drive same race/ethnicity sexual partnering among PWID. Future empirical evidence linking these associations directly or indirectly (via place-level mediators) to HIV/STI transmission will determine how eliminating discriminatory housing policies impact HIV/STI transmission.

Utilizing Electronic Laboratory Reporting Data to Assess the Burden of Hepatitis C in Arizona.

CONTEXT: Hepatitis C virus (HCV) infections must be reported to public health departments in Arizona; however, Arizona Department of Health Services has not had the resources to conduct comprehensive HCV surveillance since 2008 and thus monitoring HCV is difficult. Cases were traditionally reported via mail, fax, or telephone; however, beginning in 2009, clinical laboratories could report HCV results through electronic laboratory reporting (ELR). OBJECTIVE: To assess completeness of ELR in capturing HCV case reports and its utility for HCV surveillance and describing the current burden of HCV. DESIGN: Two components of study: (1) HCV reporting from all sources for 2 months in 2015 was de-duplicated at the patient level and cross-matched with the 1998-2008 database and 2009-2015 ELR data to identify cases newly reported during the 2-month period and calculate the proportion reported through ELR. (2) HCV ELR results during 2009-2015 were similarly de-duplicated and compared with the 1998-2008 database to identify newly reported cases. SETTING: Hepatitis C virus patients reported to Arizona Department of Health Services. PARTICIPANTS: Hepatitis C virus case patients reported during 1998-2008 and through ELR during 2009-2015. Hepatitis C virus patients through paper reports for January and June 2015. MAIN OUTCOME MEASURES: (1) Using 2 months of all HCV reporting in 2015 to examine the proportion of cases captured by ELR and the differences in the type of reports captured by ELR and non-ELR sources only. (2) Compared sex, birth year, viral load, and genotype from ELR-only data to other surveillance data. RESULTS: Electronic laboratory reporting accounted for 1260 (64%) HCV cases newly reported during the 2 months, with 698 (36%) newly identified from non-ELR sources only. Based on these findings, an estimated 11 534 HCV cases were newly reported in 2015 (172 cases per 100 000 population). During 2009-2015, a substantial amount (23%) of newly reported cases were among persons born after 1978. CONCLUSIONS: Utilizing ELR data alone can provide meaningful HCV surveillance and offers a less resource-intensive means to describe HCV burden and identify trends in newly reported cases. An assessment like this one can provide a tool for HCV monitoring in other jurisdictions that lack resources for HCV surveillance as more laboratories transition to ELR.

GTS-21 attenuates loss of body mass, muscle mass, and function in rats having systemic inflammation with and without disuse atrophy.

Muscle changes of critical illness are attributed to systemic inflammatory responses and disuse atrophy. GTS-21 (3-(2,4-dimethoxy-benzylidene)anabaseine), also known as DMBX-A) is a synthetic derivative of the natural product anabaseine that acts as an agonist at α7-acetylcholine receptors (α7nAChRs). Hypothesis tested was that modulation of inflammation by agonist GTS-21 (10 mg/kg b.i.d. intraperitoneally) will attenuate body weight (BW) and muscle changes. Systemic sham inflammation was produced in 125 rats by Cornyebacterium parvum (C.p.) or saline injection on days 0/4/8. Seventy-four rats had one immobilized-limb producing disuse atrophy. GTS-21 effects on BW, tibialis muscle mass (TMM), and function were assessed on day 12. Systemically, methemoglobin levels increased 26-fold with C.p. (p < 0.001) and decreased significantly (p < 0.033) with GTS-21. Control BW increased (+ 30 ± 9 g, mean ± SD) at day 12, but decreased with C.p. and superimposed disuse (p = 0.005). GTS-21 attenuated BW loss in C.p. (p = 0.005). Compared to controls, TMM decreased with C.p. (0.43 ± 0.06 g to 0.26 ± 0.03 g) and with superimposed disuse (0.18 ± 0.04 g); GTS-21 ameliorated TMM loss to 0.32 ± 0.04 (no disuse, p = 0.028) and to 0.22 ± 0.03 (with disuse, p = 0.004). Tetanic tensions decreased with C.p. or disuse and GTS-21 attenuated tension decrease in animals with disuse (p = 0.006) and in animals with C.p. and disuse (p = 0.029). C.p.-induced 11-fold increased muscle α7nAChR expression was decreased by > 60% with GTS-21 treatment. In conclusion, GTS-21 modulates systemic inflammation, evidenced by both decreased methemoglobin levels and decrease of α7nAChR expression, and mitigates inflammation-mediated loss of BW, TMM, fiber size, and function.

Testing for coccidioidomycosis in emergency departments in Arizona.

Testing practices for coccidioidomycosis in the emergency department are poorly understood. We described characteristics of patients tested for coccidioidomycosis in emergency departments in Arizona and examined coccidioidomycosis testing among community-acquired pneumonia (CAP) patients. Emergency department visit records for patients tested for coccidioidomycosis and CAP patients were extracted from the Arizona hospital discharge database. In sum, 2.8% of CAP patients were tested for coccidioidomycosis. The proportion of patients tested varied substantially by healthcare facility and provider.

Strategies to Improve Start Time in the Operating Theatre: a Systematic Review.

Operating theatres represent a significant cost burden for healthcare providers around the world. Theatre start time is widely acknowledged as an important target for efficiency savings. However, there is uncertainty surrounding the effectiveness of strategies to improve start time, and questions regarding the barriers to their implementation. We conducted a systematic review of bibliographic databases to identify primary research papers assessing the effect of interventions on theatre start time. Two hundred and nine papers were found from electronic literature search with 14 being included in the final review. Financial incentives, educational approaches, system-based techniques, communication, the 'golden patient' initiative and 'the productive operating theatre' scheme have all been shown to improve start time. However, questions remain over which is the most effective, the longevity of their effects and whether the results can be extrapolated beyond the context in which they were studied. We summarise the key approaches reported in the literature and identify areas for future research. This is of use to clinicians and hospital managers seeking to improve efficiency and achieve cost savings.

Species richness effects on grassland recovery from drought depend on community productivity in a multisite experiment.

Biodiversity can buffer ecosystem functioning against extreme climatic events, but few experiments have explicitly tested this. Here, we present the first multisite biodiversity × drought manipulation experiment to examine drought resistance and recovery at five temperate and Mediterranean grassland sites. Aboveground biomass production declined by 30% due to experimental drought (standardised local extremity by rainfall exclusion for 72-98 consecutive days). Species richness did not affect resistance but promoted recovery. Recovery was only positively affected by species richness in low-productive communities, with most diverse communities even showing overcompensation. This positive diversity effect could be linked to asynchrony of species responses. Our results suggest that a more context-dependent view considering the nature of the climatic disturbance as well as the productivity of the studied system will help identify under which circumstances biodiversity promotes drought resistance or recovery. Stability of biomass production can generally be expected to decrease with biodiversity loss and climate change.

Whole-Exome Sequencing Analyses of Inflammatory Bowel Disease-Associated Colorectal Cancers.

BACKGROUND & AIMS: A long duration of inflammatory bowel disease (IBD) increases the risk for colorectal cancer. Mutation analysis of limited numbers of genes has indicated that colorectal tumors that develop in patients with IBD differ from those of patients without IBD. We performed whole-exome sequencing analyses to characterize the genetic landscape of these tumors. METHODS: We collected colorectal tumor and non-neoplastic tissues from 31 patients with IBD and colorectal cancer (15 with ulcerative colitis, 14 with Crohn's disease, and 2 with indeterminate colitis) and performed whole-exome sequencing analyses of the microdissected tumor and matched nontumor tissues. We identified somatic alterations by comparing matched specimens. The prevalence of mutations in sporadic colorectal tumors was obtained from previously published exome-sequencing studies. RESULTS: Two specimens had somatic mutations in the DNA proofreading or mismatch repair genes POLE, MLH1, and MSH6 and the tumor cells had a hypermutable phenotype. The remaining tumors had, on average, 71 alterations per sample. TP53 was the most commonly mutated gene, with prevalence similar to that of sporadic colorectal tumors (63% of cases). However, tumors from the patients with IBD had a different mutation spectrum. APC and KRAS were mutated at significantly lower rates in tumors from patients with IBD than in sporadic colorectal tumors (13% and 20% of cases, respectively). Several genes were mutated more frequently or uniquely in tumors from patients with IBD, including SOX9 and EP300 (which encode proteins in the WNT pathway), NRG1 (which encodes an ERBB ligand), and IL16 (which encodes a cytokine). Our study also revealed recurrent mutations in components of the Rho and Rac GTPase network, indicating a role for noncanonical WNT signaling in development of colorectal tumors in patients with IBD. CONCLUSIONS: Colorectal tumors that develop in patients with IBD have distinct genetic features from sporadic colorectal tumors. These findings could be used to develop disease-specific markers for diagnosis and treatment of patients with IBD and colorectal cancer.

Plant responses to climatic extremes: within-species variation equals among-species variation.

Within-species and among-species differences in growth responses to a changing climate have been well documented, yet the relative magnitude of within-species vs. among-species variation has remained largely unexplored. This missing comparison impedes our ability to make general predictions of biodiversity change and to project future species distributions using models. We present a direct comparison of among- versus within-species variation in response to three of the main stresses anticipated with climate change: drought, warming, and frost. Two earlier experiments had experimentally induced (i) summer drought and (ii) spring frost for four common European grass species and their ecotypes from across Europe. To supplement existing data, a third experiment was carried out, to compare variation among species from different functional groups to within-species variation. Here, we simulated (iii) winter warming plus frost for four grasses, two nonleguminous, and two leguminous forbs, in addition to eleven European ecotypes of the widespread grass Arrhenatherum elatius. For each experiment, we measured: (i) C/N ratio and biomass, (ii) chlorophyll content and biomass, and (iii) plant greenness, root (15) N uptake, and live and dead tissue mass. Using coefficients of variation (CVs) for each experiment and response parameter, a total of 156 within- vs. among-species comparisons were conducted, comparing within-species variation in each of four species with among-species variation for each seed origin (five countries). Of the six significant differences, within-species CVs were higher than among-species CVs in four cases. Partitioning of variance within each treatment in two of the three experiments showed that within-species variability (ecotypes) could explain an additional 9% of response variation after accounting for the among-species variation. Our observation that within-species variation was generally as high as among-species variation emphasizes the importance of including both within- and among-species variability in ecological theory (e.g., the insurance hypothesis) and for practical applications (e.g., biodiversity conservation).

Clinical management of proliferative vitreoretinopathy: an update.

BACKGROUND: Proliferative vitreoretinopathy (PVR) remains the most significant obstacle to successful retinal reattachment surgery. Preclinical studies continue to add insights into the complex molecular events leading to PVR development, helping to identify new targets for potential prophylactic or therapeutic agents. This article reviews the recent evidence supporting surgical and medical treatments for PVR. METHODS: PUBMED was used for literature search. Clinical studies regarding surgical management of PVR from January 1, 2000 to August 1, 2014 were included. Clinical studies regarding medical management of PVR from January 1, 2000 to August 1, 2014 were included if the design of study was a randomized controlled trial. RESULTS: Many recent studies have evaluated surgical and medical strategies for the treatment and prevention of PVR. Newer vitreoretinal surgery technology (23- and 25-gauge vitrectomy) and tamponade agents (heavy silicone oils) have been studied. Medical therapies evaluated include antiinflammatory agents, low molecular weight heparin, 5-fluorouracil, 13-cis-retinoic acid, and daunorubicin, amongst others. CONCLUSION: Surgical management with pars plana vitrectomy, with or without scleral buckle or inferior retinectomy, remains an effective treatment for PVR-related detachments. Consensus regarding a preferred surgical strategy remains controversial. Many medical therapies have been studied but fail to demonstrate a statistically significant benefit in clinical trials. Further studies to clarify the efficacy of available and novel treatment options are warranted.

High miR-21 expression from FFPE tissues is associated with poor survival and response to adjuvant chemotherapy in colon cancer.

Colon cancer (CC) is a leading cause of cancer mortality. Novel biomarkers are needed to identify CC patients at high risk of recurrence and those who may benefit from therapeutic intervention. The aim of this study is to investigate if miR-21 expression from RNA isolated from formalin-fixed paraffin-embedded (FFPE) tissue sections is associated with prognosis and therapeutic outcome for patients with CC. The expression of miR-21 was measured by quantitative reverse transcriptase-polymerase chain reaction in a Japanese cohort (stage I-IV, n = 156) and a German cohort (stage II, n = 145). High miR-21 expression in tumors was associated with poor survival in both the stage II/III Japanese (p = 0.0008) and stage II German (p = 0.047) cohorts. These associations were independent of other clinical covariates in multivariable models. Receipt of adjuvant chemotherapy was not beneficial in patients with high miR-21 in either cohort. In the Japanese cohort, high miR-21 expression was significantly associated with poor therapeutic outcome (p = 0.0001) and adjuvant therapy was associated with improved survival in patients with low miR-21 (p = 0.001). These results suggest that miR-21 is a promising biomarker to identify patients with poor prognosis and can be accurately measured in FFPE tissues. The expression of miR-21 may also identify patients who will benefit from adjuvant chemotherapy.

Immobilization with atrophy induces de novo expression of neuronal nicotinic α7 acetylcholine receptors in muscle contributing to neurotransmission.

BACKGROUND: Mature acetylcholine receptor (AChR) isoform normally mediates muscle contraction. The hypothesis that α7AChRs up-regulate during immobilization and contribute to neurotransmission was tested pharmacologically using specific blockers to mature (waglerin-1), immature (αA-OIVA), and α7AChRs (methyllycaconitine), and nonspecific muscle AChR antagonist, α-bungarotoxin. METHODS: Mice were immobilized; contralateral limbs were controls. Fourteen days later, anesthetized mice were mechanically ventilated. Nerve-stimulated tibialis muscle contractions on both sides were recorded, and blockers enumerated above sequentially administered via jugular vein. Data are mean ± standard error. RESULTS: Immobilization (N = 7) induced tibialis muscle atrophy (40.6 ± 2.8 vs. 52.1 ± 2.0 mg; P < 0.01) and decrease of twitch tension (34.8 ± 1.1 vs. 42.9 ± 1.5 g; P < 0.01). Waglerin-1 (0.3 ± 0.05 µg/g) significantly (P = 0.001; N = 9) depressed twitch tension on contralateral (≥97%) versus immobilized side (approximately 45%). Additional waglerin-1 (total dose 1.06 ± 0.12 µg/g or approximately 15.0 × ED50 in normals) could not depress twitch of 80% or greater on immobilized side. Immature AChR blocker, αA-OIVA (17.0 ± 0.25 µg/g) did not change tension bilaterally. Administration of α-bungarotoxin (N = 4) or methyllycaconitine (N = 3) caused 96% or greater suppression of the remaining twitch tension on immobilized side. Methyllycaconitine, administered first (N = 3), caused equipotent inhibition by waglerin-1 on both sides. Protein expression of α7AChRs was significantly (N = 3; P < 0.01) increased on the immobilized side. CONCLUSIONS: Ineffectiveness of waglerin-1 suggests that the twitch tension during immobilization is maintained by receptors other than mature AChRs. Because αA-OIVA caused no neuromuscular changes, it can be concluded that immature AChRs contribute minimally to neurotransmission. During immobilization approximately 20% of twitch tension is maintained by up-regulation of α-bungarotoxin- and methyllycaconitine-sensitive α7AChRs.