RESUMEN
BACKGROUND: Biliary tract cancer (BTC) is a highly heterogeneous aggressive tumor, and advanced patients have poor prognosis. This work aimed to evaluate the efficacy and safety of camrelizumab combined with chemotherapy in treating advanced BTC, and to explore predictive biomarkers for distinguishing effective population. METHODS: 183 advanced BTC patients admitted from September 2018 to September 2021 were retrospectively selected. 93 patients were treated with camrelizumab combined with chemotherapy (C+C group) and 90 patients were treated with chemotherapy alone (C group). Objective response rate (ORR), disease control rate (DCR), median progression-free survival (mPFS), and median overall survival (mOS) were analyzed between two groups. Peripheral blood lymphocyte subsets were assessed by flow cytometry pre- and post-treatment. RESULTS: The mPFS (6.9 months) and mOS (12.1 months) in the C+C group were significantly longer than those in the C group, which were 5.2 months and 9.8 months respectively (HR 0.46, 95% CI 0.38-0.54, p=0.017; HR 0.39, 95% CI 0.32-0.47, p=0.033). The percentage of Total T, CD4+T, natural killer (NK) cells, lymphocyte, and CD4+/CD8+ cell ratios were significantly increased in effective patients after C+C treatment, but didn't increase in progressive disease (PD) patients. Higher percentage of Total T, CD4+T, and higher CD4+/CD8+ cell ratios post-treatment were associated with longer OS. CONCLUSIONS: Camrelizumab combining chemotherapy significantly prolonged the mPFS and mOS of advanced BTC patients. Immunotherapy may improve the immune status of advanced patients, and immunotherapy efficacy might be predicted based on the peripheral blood lymphocyte subsets.
RESUMEN
PURPOSE: The rat cervicitis model was established with 20% phenol glue to explore the therapeutic effect of Kangfuxiaomi shuan II on rat cervicitis and its mechanism. METHODS: After modeling, the rats were treated with Shuangzuotai suppository (37.84 mg/kg), Kangfuxiaoyan shuan (205.6 mg/kg) and Kangfuxiaomi shuan II (40, 80, 160 mg/kg). The histopathological changes and injury degree of cervix in rats were evaluated by vulvar inflammation score and organ index. The therapeutic effect of Kangfuxiaomi shuan II on cervicitis was evaluated by detecting the levels of copper-protein (CP), C-reactive protein (CRP), Rat interleukin 6 (IL-6), superoxide dismutase (SOD) and malondialdehyde (MDA) in serum and epidermal growth factor (EGF), cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in cervical tissue. RESULTS: Compared with the model group, the vulvar inflammation score and cervical index of rats in other groups decreased significantly (P<0.01). Kangfuxiaomi shuan II could significantly reduce the levels of CP, CRP, and MDA in serum of rats with cervicitis, and significantly increase the activity of SOD in serum of rats with cervicitis (P<0.01). The levels of EGF and iNOS in cervical tissue of rats also increased in different degrees, while the level of COX-2 decreased significantly (P<0.01), which significantly improved the pathological degree of vulvar inflammation in rats with cervicitis. CONCLUSIONS: Kangfuxiaomi shuan II has a certain therapeutic effect on cervicitis in rats, and its mechanism may be related to the regulation of inflammatory cytokine network and immunity.
Asunto(s)
Cervicitis Uterina , Animales , Ciclooxigenasa 2/metabolismo , Femenino , Malondialdehído , Óxido Nítrico Sintasa de Tipo II/metabolismo , Ratas , Superóxido Dismutasa/metabolismo , Cervicitis Uterina/tratamiento farmacológicoRESUMEN
Preexploitation shark baselines and the history of human impact on coral reef-associated shark communities in the Caribbean are tpoorly understood. We recovered shark dermal denticles from mid-Holocene (â¼7 ky ago) and modern reef sediments in Bocas del Toro, Caribbean Panama, to reconstruct an empirical shark baseline before major human impact and to quantify how much the modern shark community in the region had shifted from this historical reference point. We found that denticle accumulation rates, a proxy for shark abundance, declined by 71% since the mid-Holocene. All denticle morphotypes, which reflect shark community composition, experienced significant losses, but those morphotypes found on fast-swimming, pelagic sharks (e.g., families Carcharhinidae and Sphyrnidae) declined the most. An analysis of historical records suggested that the steepest decline in shark abundance occurred in the late 20th century, coinciding with the advent of a targeted shark fishery in Panama. Although the disproportionate loss of denticles characterizing pelagic sharks was consistent with overfishing, the large reduction in denticles characterizing demersal species with low commercial value (i.e., the nurse shark Ginglymostoma cirratum) indicated that other stressors could have exacerbated these declines. We demonstrate that the denticle record can reveal changes in shark communities over long ecological timescales, helping to contextualize contemporary abundances and inform shark management and ecology.
Asunto(s)
Escamas de Animales , Arrecifes de Coral , Fósiles , Tiburones/fisiología , Escamas de Animales/citología , Escamas de Animales/fisiología , Animales , Región del Caribe , Conservación de los Recursos Naturales , Sedimentos Geológicos/química , Actividades Humanas , Humanos , Panamá , Tiburones/clasificación , Factores de TiempoRESUMEN
ABSTRACT Purpose: The rat cervicitis model was established with 20% phenol glue to explore the therapeutic effect of Kangfuxiaomi shuan II on rat cervicitis and its mechanism. Methods: After modeling, the rats were treated with Shuangzuotai suppository (37.84 mg/kg), Kangfuxiaoyan shuan (205.6 mg/kg) and Kangfuxiaomi shuan II (40, 80, 160 mg/kg). The histopathological changes and injury degree of cervix in rats were evaluated by vulvar inflammation score and organ index. The therapeutic effect of Kangfuxiaomi shuan II on cervicitis was evaluated by detecting the levels of copper-protein (CP), C-reactive protein (CRP), Rat interleukin 6 (IL-6), superoxide dismutase (SOD) and malondialdehyde (MDA) in serum and epidermal growth factor (EGF), cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in cervical tissue. Results: Compared with the model group, the vulvar inflammation score and cervical index of rats in other groups decreased significantly (P<0.01). Kangfuxiaomi shuan II could significantly reduce the levels of CP, CRP, and MDA in serum of rats with cervicitis, and significantly increase the activity of SOD in serum of rats with cervicitis (P<0.01). The levels of EGF and iNOS in cervical tissue of rats also increased in different degrees, while the level of COX-2 decreased significantly (P<0.01), which significantly improved the pathological degree of vulvar inflammation in rats with cervicitis. Conclusions: Kangfuxiaomi shuan II has a certain therapeutic effect on cervicitis in rats, and its mechanism may be related to the regulation of inflammatory cytokine network and immunity.
Asunto(s)
Animales , Femenino , Ratas , Cervicitis Uterina/tratamiento farmacológico , Superóxido Dismutasa/metabolismo , Ciclooxigenasa 2/metabolismo , Óxido Nítrico Sintasa de Tipo II/metabolismo , MalondialdehídoRESUMEN
Caribbean Acropora spp. corals have undergone a decline in cover since the second half of the twentieth century. Loss of these architecturally complex and fast-growing corals has resulted in significant, cascading changes to the character, diversity, and available eco-spaces of Caribbean reefs. Few thriving Acropora spp. populations exist today in the Caribbean and western North Atlantic seas, and our limited ability to access data from reefs assessed via long-term monitoring efforts means that reef scientists are challenged to determine resilience and longevity of existing Acropora spp. reefs. Here we used multiple dating methods to measure reef longevity and determine whether Coral Gardens Reef, Belize, is a refuge for Acropora cervicornis against the backdrop of wider Caribbean decline. We used a new genetic-aging technique to identify sample sites, and radiocarbon and high-precision uranium-thorium (U-Th) dating techniques to test whether one of the largest populations of extant A. cervicornis in the western Caribbean is newly established after the 1980s, or represents a longer-lived, stable population. We did so with respect for ethical sampling of a threatened species. Our data show corals ranging in age from 1910 (14C) or 1915 (230Th) to at least November 2019. While we cannot exclude the possibility of short gaps in the residence of A. cervicornis earlier in the record, the data show consistent and sustained living coral throughout the 1980s and up to at least 2019. We suggest that Coral Gardens has served as a refuge for A. cervicornis and that identifying other, similar sites may be critical to efforts to grow, preserve, conserve, and seed besieged Caribbean reefs.
Asunto(s)
Antozoos/fisiología , Conservación de los Recursos Naturales , Arrecifes de Coral , Refugio de Fauna , Animales , Belice , Región del Caribe , Especies en Peligro de Extinción , Dinámica PoblacionalRESUMEN
Many Caribbean coral reefs are heavily degraded, yet their pre-human, natural states are often assumed or estimated using space-for-time substitution approaches. Here we use an 11-hectare suite of fossilised mid-Holocene (7.2-5.6 ka) fringing reefs in Caribbean Panama to define natural variation in hard coral community structure before human-impact to provide context to the states of the same reefs today. We collected bulk samples from four trenches dug into the mid-Holocene fossil reef and surficial bulk samples from 2-10 m depths on five adjacent modern reefs extending over 5 km. Analysis of the abundances of coral taxa in fossil bulk samples define the Historical Range of Variation (HRV) in community structure of the reefs. When compared to the community structure of adjacent modern reefs, we find that most coral communities today fall outside the HRV, identifying them as novel ecosystems and corroborating the well-documented transition from acroporid-dominated Caribbean reefs to reefs dominated by stress-tolerant taxa (Porites and Agaricia). We find one modern reef, however, whose community composition remains within the HRV showing that it has not transitioned to a novel state. Reef-matrix cores extracted from this reef reveal that the coral community has remained in this state for over 800 years, suggesting long-term stability and resistance to the region-wide shift to novel states. Without these data to provide historical context, this potentially robust and stable reef would be overlooked since it does not fulfil expectations of what a Caribbean coral reef should look like in the absence of humans. This example illustrates how defining past variation using the fossil record can improve our understanding of modern degradation and guide conservation.
Asunto(s)
Antozoos/fisiología , Conservación de los Recursos Naturales , Ecosistema , Animales , Región del Caribe , Fósiles , Humanos , Factores de TiempoRESUMEN
OBJECTIVE: To characterize the dosing and safety of off-label caffeine citrate in a contemporary cohort of extremely premature infants. STUDY DESIGN: We used electronic health records (2010-2013) from 4 neonatal intensive care units to identify infants of ≤28 weeks of gestational age exposed to caffeine citrate. Safety outcomes included death, bronchopulmonary dysplasia, necrotizing enterocolitis, spontaneous intestinal perforation, intraventricular hemorrhage, patent ductus arteriosus ligation, seizures, and arrhythmias. We used multivariable logistic regression to evaluate the association of caffeine citrate exposure with clinical events. RESULTS: Of 410 infants with a median (IQR) gestational age of 26 (24-27) weeks, 95% received caffeine citrate for >0 days. Infants received a median (IQR) daily dose of 8 (5-10) mg/kg/day. Incidences of clinical events on day of caffeine citrate exposure were death 2%, patent ductus arteriosus ligation 12%, and medical and surgical necrotizing enterocolitis 5% and 4%, respectively. Bronchopulmonary dysplasia occurred in 37% of infants and was not associated with caffeine dose. Increased caffeine citrate dose was associated with lower odds of patent ductus arteriosus ligation and necrotizing enterocolitis. CONCLUSIONS: Caffeine citrate was used in extremely premature infants at younger gestation, at higher doses, and for longer durations than recommended on the drug label. Increased caffeine citrate exposure, dose, or therapy duration was not associated with increased risk of necrotizing enterocolitis.
Asunto(s)
Apnea/tratamiento farmacológico , Cafeína/administración & dosificación , Cafeína/efectos adversos , Citratos/administración & dosificación , Citratos/efectos adversos , Enfermedades del Prematuro/tratamiento farmacológico , Uso Fuera de lo Indicado , Displasia Broncopulmonar/complicaciones , Hemorragia Cerebral/complicaciones , Conducto Arterioso Permeable/complicaciones , Registros Electrónicos de Salud , Enterocolitis Necrotizante/complicaciones , Femenino , Edad Gestacional , Humanos , Recien Nacido Extremadamente Prematuro , Recién Nacido de Bajo Peso , Recién Nacido , Recien Nacido Prematuro , Unidades de Cuidado Intensivo Neonatal , Cuidado Intensivo Neonatal , Masculino , Análisis Multivariante , Resultado del TratamientoRESUMEN
The western corn rootworm (WCR) Diabrotica virgifera virgifera causes substantial damage in corn. Genetically modified (GM) plants expressing some Bacillus thuringiensis (Bt) insecticidal Cry proteins efficiently controlled this pest. However, changes in WCR susceptibility to these Bt traits have evolved and identification of insecticidal proteins with different modes of action against WCR is necessary. We show here for the first time that Cyt1Aa from Bt exhibits toxicity against WCR besides to the dipteran Aedes aegypti larvae. Cyt1Aa is a pore-forming toxin that shows no cross-resistance with mosquitocidal Cry toxins. We characterized different mutations in helix α-A from Cyt1Aa. Two mutants (A61C and A59C) exhibited reduced or absent hemolytic activity but retained toxicity to A. aegypti larvae, suggesting that insecticidal and hemolytic activities of Cyt1Aa are independent activities. These mutants were still able to form oligomers in synthetic lipid vesicles and to synergize Cry11Aa toxicity. Remarkably, mutant A61C showed a five-fold increase insecticidal activity against mosquito and almost 11-fold higher activity against WCR. Cyt1Aa A61C mutant was as potent in killing WCR that were selected for resistance to mCry3A as it was against unselected WCR indicating that this toxin could be a useful resistance management option in the control of WCR.
Asunto(s)
Bacillus thuringiensis , Proteínas Bacterianas , Escarabajos/crecimiento & desarrollo , Endotoxinas , Proteínas Hemolisinas , Mutación Missense , Control Biológico de Vectores , Animales , Bacillus thuringiensis/genética , Bacillus thuringiensis/metabolismo , Toxinas de Bacillus thuringiensis , Proteínas Bacterianas/genética , Proteínas Bacterianas/toxicidad , Endotoxinas/genética , Endotoxinas/toxicidad , Proteínas Hemolisinas/genética , Proteínas Hemolisinas/toxicidad , Insecticidas/toxicidadRESUMEN
Local adaptation is a critical evolutionary process that allows plants to grow better in their local compared to non-native habitat and results in species-wide geographic patterns of adaptive genetic variation. For forest tree species with a long generation time, this spatial genetic heterogeneity can shape the ability of trees to respond to rapid climate change. Here, we identify genomic variation that may confer local environmental adaptations and then predict the extent of adaptive mismatch under future climate as a tool for forest restoration or management of the widely distributed high-elevation oak species Quercus rugosa in Mexico. Using genotyping by sequencing, we identified 5,354 single nucleotide polymorphisms (SNPs) genotyped from 103 individuals across 17 sites in the Trans-Mexican Volcanic Belt, and, after controlling for neutral genetic structure, we detected 74 F ST outlier SNPs and 97 SNPs associated with climate variation. Then, we deployed a nonlinear multivariate model, Gradient Forests, to map turnover in allele frequencies along environmental gradients and predict areas most sensitive to climate change. We found that spatial patterns of genetic variation were most strongly associated with precipitation seasonality and geographic distance. We identified regions of contemporary genetic and climatic similarities and predicted regions where future populations of Q. rugosa might be at risk due to high expected rate of climate change. Our findings provide preliminary details for future management strategies of Q. rugosa in Mexico and also illustrate how a landscape genomic approach can provide a useful tool for conservation and resource management strategies.
RESUMEN
Anthocyanins are naturally occurring flavonoids derived from the phenylpropanoid pathway. There is increasing evidence of the preventative and protective roles of anthocyanins against a broad range of pathologies, including different cancer types and metabolic diseases. However, most of the fresh produce available to consumers typically contains only small amounts of anthocyanins, mostly limited to the epidermis of plant organs. Therefore, transgenic and non-transgenic approaches have been proposed to enhance the levels of this phytonutrient in vegetables, fruits, and cereals. Here, were review the current literature on the anthocyanin biosynthesis pathway in model and crop species, including the structural and regulatory genes involved in the differential pigmentation patterns of plant structures. Furthermore, we explore the genetic regulation of anthocyanin biosynthesis and the reasons why it is strongly repressed in specific cell types, in order to create more efficient breeding strategies to boost the biosynthesis and accumulation of anthocyanins in fresh fruits and vegetables.
Asunto(s)
Antocianinas/biosíntesis , Frutas/metabolismo , Regulación de la Expresión Génica de las Plantas/genética , Plantas/metabolismo , Verduras/metabolismo , Antocianinas/química , Antocianinas/genética , Cruzamiento , Frutas/química , Plantas/química , Verduras/químicaRESUMEN
OBJECTIVE: To assess appropriate pantoprazole dosing for obese children, we conducted a prospective pharmacokinetics (PK) investigation of pantoprazole in obese children, a patient population that is traditionally excluded from clinical trials. STUDY DESIGN: A total of 41 obese children (6-17 years of age), genotyped for CYP2C19 variants *2, *3, *4, and *17, received a single oral dose of pantoprazole, ~1.2 mg/kg lean body weight (LBW), with LBW calculated via a validated formula. Ten post-dose pantoprazole plasma concentrations were measured, and PK variables generated via noncompartmental methods (WinNonlin). Linear and nonlinear regression analyses and analyses of variance were used to explore obesity, age, and CYP2C19 genotype contribution to pantoprazole PK. PK variables of interest were compared with historic nonobese peers treated with pantoprazole. RESULTS: Independent of genotype, when normalized to dose per kg total body weight, pantoprazole apparent clearance and apparent volume of distribution were significantly lower (P < .05) and systemic exposure significantly higher (P < .01) in obese vs nonobese children. When normalized per kg LBW, these differences were not evident in children ≥12 years of age and markedly reduced in children <12 years of age. CONCLUSIONS: LBW dosing of pantoprazole led to pantoprazole PK similar to nonobese peers. Additional factors, other than body size (eg, age-related changes in CYP2C19 activity), appear to affect pantoprazole PK in children <12 years of age. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02186652.
Asunto(s)
Reflujo Gastroesofágico/tratamiento farmacológico , Pantoprazol/farmacocinética , Obesidad Infantil/tratamiento farmacológico , Inhibidores de la Bomba de Protones/farmacocinética , Administración Oral , Adolescente , Área Bajo la Curva , Peso Corporal , Niño , Citocromo P-450 CYP2C19/genética , Cálculo de Dosificación de Drogas , Femenino , Reflujo Gastroesofágico/complicaciones , Genotipo , Humanos , Masculino , Pantoprazol/administración & dosificación , Obesidad Infantil/complicaciones , Obesidad Infantil/genética , Estudios Prospectivos , Inhibidores de la Bomba de Protones/administración & dosificaciónRESUMEN
PURPOSE:: To investigate the mechanisms by which PD98059 and LY294002 interfere with the abnormal deposition of extracellular matrix regulated by connective tissue growth factor (CTGF) of rat pulmonary artery smooth muscle cells (PASMCs). METHODS:: Rat PASMCs were cultured and separated into a control group. Real-time fluorescence quantitative PCR was performed to detect the expression of collagen III and fibronectin mRNA. Immunohistochemistry and western blot analyses were performed to detect the expression of collagen III protein. RESULTS:: The expression of collagen III and fibronectin mRNA was greater in PASMCs stimulated with CTGF for 48 h, than in the control group. After 72h of stimulation, the expression of collagen III protein in the PASMCs was greater than in the control. The equivalent gene and protein expression of the CPL group were much more significant. CONCLUSIONS:: CTGF can stimulate the gene expression of collagen III and fibronectin in PASMCs, which may be one of the factors that promote pulmonary vascular remodeling (PVR) under the conditions of pulmonary arterial hypertension (PAH). PD98059 and LY294002 can inhibit the ERK1/2 and PI3K/PKB signaling pathways, respectively, thus interfering with the biological effects of CTGF. This may be a new way to reduce PAH-PVR.
Asunto(s)
Cromonas/farmacología , Colágeno Tipo III/metabolismo , Factor de Crecimiento del Tejido Conjuntivo/farmacología , Fibronectinas/metabolismo , Flavonoides/farmacología , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Morfolinas/farmacología , Miocitos del Músculo Liso/efectos de los fármacos , Fosfatidilinositol 3-Quinasas/efectos de los fármacos , Inhibidores de Proteínas Quinasas/farmacología , Proteínas Proto-Oncogénicas c-akt/efectos de los fármacos , Arteria Pulmonar/efectos de los fármacos , Animales , Células Cultivadas , Colágeno Tipo III/genética , Factor de Crecimiento del Tejido Conjuntivo/metabolismo , Fibronectinas/genética , Expresión Génica/efectos de los fármacos , Regulación de la Expresión Génica , Masculino , Modelos Animales , Miocitos del Músculo Liso/citología , Miocitos del Músculo Liso/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Arteria Pulmonar/citología , Arteria Pulmonar/metabolismo , Ratas Sprague-DawleyRESUMEN
Purpose: To investigate the mechanisms by which PD98059 and LY294002 interfere with the abnormal deposition of extracellular matrix regulated by connective tissue growth factor (CTGF) of rat pulmonary artery smooth muscle cells (PASMCs). Methods: Rat PASMCs were cultured and separated into a control group. Real-time fluorescence quantitative PCR was performed to detect the expression of collagen III and fibronectin mRNA. Immunohistochemistry and western blot analyses were performed to detect the expression of collagen III protein. Results: The expression of collagen III and fibronectin mRNA was greater in PASMCs stimulated with CTGF for 48 h, than in the control group. After 72h of stimulation, the expression of collagen III protein in the PASMCs was greater than in the control. The equivalent gene and protein expression of the CPL group were much more significant. Conclusions: CTGF can stimulate the gene expression of collagen III and fibronectin in PASMCs, which may be one of the factors that promote pulmonary vascular remodeling (PVR) under the conditions of pulmonary arterial hypertension (PAH). PD98059 and LY294002 can inhibit the ERK1/2 and PI3K/PKB signaling pathways, respectively, thus interfering with the biological effects of CTGF. This may be a new way to reduce PAH-PVR.(AU)
Asunto(s)
Animales , Ratas , Regulación de la Expresión Génica/genética , Músculo Liso Vascular , Factor de Crecimiento del Tejido Conjuntivo , Ratas/anatomía & histología , Ratas/genéticaRESUMEN
Abstract Purpose: To investigate the mechanisms by which PD98059 and LY294002 interfere with the abnormal deposition of extracellular matrix regulated by connective tissue growth factor (CTGF) of rat pulmonary artery smooth muscle cells (PASMCs). Methods: Rat PASMCs were cultured and separated into a control group. Real-time fluorescence quantitative PCR was performed to detect the expression of collagen III and fibronectin mRNA. Immunohistochemistry and western blot analyses were performed to detect the expression of collagen III protein. Results: The expression of collagen III and fibronectin mRNA was greater in PASMCs stimulated with CTGF for 48 h, than in the control group. After 72h of stimulation, the expression of collagen III protein in the PASMCs was greater than in the control. The equivalent gene and protein expression of the CPL group were much more significant. Conclusions: CTGF can stimulate the gene expression of collagen III and fibronectin in PASMCs, which may be one of the factors that promote pulmonary vascular remodeling (PVR) under the conditions of pulmonary arterial hypertension (PAH). PD98059 and LY294002 can inhibit the ERK1/2 and PI3K/PKB signaling pathways, respectively, thus interfering with the biological effects of CTGF. This may be a new way to reduce PAH-PVR.
Asunto(s)
Animales , Masculino , Flavonoides/farmacología , Cromonas/farmacología , Fibronectinas/metabolismo , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Colágeno Tipo III/metabolismo , Factor de Crecimiento del Tejido Conjuntivo/farmacología , Arteria Pulmonar/citología , Expresión Génica/efectos de los fármacos , Células Cultivadas , Regulación de la Expresión Génica , Fibronectinas/genética , Ratas Sprague-Dawley , Fosfatidilinositol 3-Quinasas/metabolismo , Modelos Animales , Colágeno Tipo III/genética , Miocitos del Músculo Liso/citología , Miocitos del Músculo Liso/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Factor de Crecimiento del Tejido Conjuntivo/metabolismoRESUMEN
As the frequency and intensity of coral mortality events increase under climate change, understanding how declines in coral cover may affect the bioerosion of reef frameworks is of increasing importance. Here, we explore decadal-scale rates of bioerosion of the framework building coral Orbicella annularis by grazing parrotfish following the 1997/1998 El Niño-related mass mortality event at Long Cay, Belize. Using high-precision U-Th dating and CT scan analysis, we quantified in situ rates of external bioerosion over a 13-year period (1998-2011). Based upon the error-weighted average U-Th age of dead O. annularis skeletons, we estimate the average external bioerosion between 1998 and 2011 as 0.92 ± 0.55 cm depth. Empirical observations of herbivore foraging, and a nonlinear numerical response of parrotfish to an increase in food availability, were used to create a model of external bioerosion at Long Cay. Model estimates of external bioerosion were in close agreement with U-Th estimates (0.85 ± 0.09 cm). The model was then used to quantify how rates of external bioerosion changed across a gradient of coral mortality (i.e., from few corals experiencing mortality following coral bleaching to complete mortality). Our results indicate that external bioerosion is remarkably robust to declines in coral cover, with no significant relationship predicted between the rate of external bioerosion and the proportion of O. annularis that died in the 1998 bleaching event. The outcome was robust because the reduction in grazing intensity that follows coral mortality was compensated for by a positive numerical response of parrotfish to an increase in food availability. Our model estimates further indicate that for an O. annularis-dominated reef to maintain a positive state of reef accretion, a necessity for sustained ecosystem function, live cover of O. annularis must not drop below a ~5-10% threshold of cover.