Background: Cyproheptadine (CY) is an antihistaminic agent that is commonly used for symptom reli... more Background: Cyproheptadine (CY) is an antihistaminic agent that is commonly used for symptom relief in skin conditions. The most common pattern of cutaneous drug eruption in children is the exanthematous type, with the penicillin family often cited. CY is also an antiserotoninergic agent with the side effect of appetite stimulation and has been used in children with poor feeding and poor weight gain. The Case: We report a case of a 31-month-old male patient seen in the outpatient setting with a diffuse morbilliform rash after use of amoxicillin for right otitis media. The patient was a post-operative congenital heart disease (CHD) patient, actively being treated with CY for feeding difficulties and low weight often seen in the CHD population. Amoxicillin was discontinued, while CY was continued. The patient did not encounter any pruritic symptoms during morbilliform rash, while weight gain of 3.1 kg occurred over a 9 months period, increasing patient from the 10th to 41st percentile...
2 Rowe SP, Gorin MA, Allaf ME et al. PET imaging of prostate-specific membrane antigen in prostat... more 2 Rowe SP, Gorin MA, Allaf ME et al. PET imaging of prostate-specific membrane antigen in prostate cancer: current state of the art and future challenges. Prostate Cancer Prostatic Dis 2016; 19: 223-30 3 Albisinni S, Artigas C, Aoun F et al. Clinical impact of 68 Ga-prostatespecific membrane antigen (PSMA) positron emission tomography/ computed tomography (PET/CT) in patients with prostate cancer with rising prostate-specific antigen after treatment with curative intent: preliminary analysis of a multidisciplinary approach. BJU Int 2017; 120: 197-203 4 van Leeuwen PJ, Stricker P, Hruby G et al. 68 Ga-PSMA has a high detection rate of prostate cancer recurrence outside the prostatic fossa in patients being considered for salvage radiation treatment.
Motor-vehicle crashes are a leading cause of death among children in the United States, and almos... more Motor-vehicle crashes are a leading cause of death among children in the United States, and almost one-fourth of all trips by school-aged children are trips to and from school. This study sought to determine how children (5-18years) travel to and from school and, among those living ≤1mile of school, to explore the role of school bus service eligibility on school travel mode. We used national 2012 survey data to determine prevalence of usual school travel mode, stratified by distance from school. For those living ≤1mile of school, multivariable regression was conducted to assess the association between bus service eligibility and walking or bicycling. Almost half (46.6%) of all children rode in passenger vehicles (PV) to school and 41.8% did so for the trip home. Results were similar among those living ≤1mile (48.1%, PV to school; 41.3%, PV to home). Among those living ≤1mile, 21.9% and 28.4% of children walked or bicycled to and from school, respectively. Ineligibility for school bus service was strongly associated with walking or bicycling to school [adjusted prevalence ratio (aPR: 5.36; p<0.001)] and from school (aPR: 5.36; p<0.001). Regardless of distance from school, passenger vehicles were a common mode of travel. For children who live close to school, the role that school bus service eligibility plays in walking or bicycling deserves further consideration. Given the large proportion of children who use passenger vehicles for school travel, effective interventions can be adopted to increase proper child restraint and seat belt use and reduce crash risks among teen drivers. Better understanding of conditions under which bus service is offered to children who live close to school could inform efforts to improve pedestrian and bicyclist safety for school travel.
Few studies have focused on the bacterial species associated with the deterioration of the dental... more Few studies have focused on the bacterial species associated with the deterioration of the dental and gingival health of children with congenital heart defects (CHD). The aims of this study were (1) to examine the dental plaque of children with CHD in order to quantify bacterial load and altered bacterial composition compared with children without CHD; and (2) to investigate the correlation between the level of caries and gingivitis and dental biofilm bacteria among those children. In this cross-sectional study, participants were children (3-12 years) recruited in Khartoum State, Sudan. A total of 80 CHD cases from the Ahmed Gasim Cardiac Centre and 80 healthy controls from randomly selected schools and kindergartens were included. Participants underwent clinical oral examinations for caries (decayed, missing, and filled teeth indices [DMFT] for primary dentition, and DMFT for permanent dentition), and gingivitis (simplified gingival index [GI]). Pooled dental biofilm samples were o...
Using a robust series of 2511 patients followed for a median time of 9.0 yr, Stewart-Merrill et a... more Using a robust series of 2511 patients followed for a median time of 9.0 yr, Stewart-Merrill et al proposed a novel approach that enables a tailored follow-up strategy following surgical resection of clinically localized renal cell carcinoma (RCC). By means of competing risk models incorporating age, Charlson comorbidity index (CCI), pathologic tumor stage, and recurrence location (abdomen, chest, bone, other), the authors determined the points in time at which the patient's risk of dying from a non-RCC cause exceeded that of recurrence. They found considerable variability in those time points. Among patients with pT1Nx-0 disease who had CCI <1, for example, the risk of non-RCC death began to exceed that of abdominal recurrence at 7 yr for patients aged 50-59 yr, at 2.5 yr for patients aged 60-69 yr, and at 6 mo for patients aged !80 yr. The authors concluded that their competing risks model allows for better prediction and offers an individualized surveillance strategy based on the patient's health status and cancer characteristics. This risk-adapted approach offers the advantage of forgoing unnecessary follow-up when not needed and prolonging it when necessary but not recommended by current guidelines.
Angiogenesis is critical for tumor growth and survival and involves interactions between cancer a... more Angiogenesis is critical for tumor growth and survival and involves interactions between cancer and endothelial cells. Prostate-specific membrane antigen (PSMA/FOLH1) is expressed in the neovasculature of several types of cancer. However, the study of neovascular PSMA expression has been impeded as human umbilical vein endothelial cell (HUVEC) cultures are PSMA-negative and both tumor xenografts and patient-derived xenograft (PDX) models are not known to express PSMA in their vasculature. Therefore, PSMA expression was examined in HUVECs, in vitro and in vivo, and we tested the hypothesis that cancer cell-HUVEC crosstalk could induce the expression of PSMA in HUVECs. Interestingly, conditioned media from several cancer cell lines induced PSMA expression in HUVECs, in vitro, and these lines induced PSMA, in vivo, in a HUVEC co-implantation mouse model. Furthermore, HUVECs in which PSMA expression was induced were able to internalize J591, a monoclonal antibody (mAb) that recognizes a...
In 2010, the Deepwater Horizon (DWH) oil spill adversely impacted many communities along the Gulf... more In 2010, the Deepwater Horizon (DWH) oil spill adversely impacted many communities along the Gulf of Mexico. Effects on Gulf waters, marshes, aquatic life, and fisheries were evident in the following days, months, and years. Through studying affected communities' perceptions regarding the DWH accident, we aim to identify behavioral changes, understand public information sources, and inform dissemination strategies that improve communications from regulatory agencies. Over a three-year period (2012-2015), residents (n = 192) from 7 coastal parishes in southeast Louisiana were surveyed about their perceptions and behaviors before, during, and after the DWH accident. Self-reported consumption of local seafood decreased significantly (50%) during the DWH oil spill but returned to pre-event reported levels by 2015. However, negative seafood quality perceptions remain and have not returned to what were generally positive pre-event levels. Over 30% of study participants trust relatives...
Objective: Uncontrolled host defense mechanisms can significantly impede tissue engineering, rege... more Objective: Uncontrolled host defense mechanisms can significantly impede tissue engineering, regeneration and reconstruction of oral and craniofacial tissues. The anti-inflammatory and pro-resolving actions of lipoxins and resolvins have already been documented in several preclinical models of inflammatory diseases including periodontal disease. The aim of this study was to evaluate the potential of Novel Pro-Resolving-Medicines (NPRMs) containing a lipoxin A4 (LXA4) analog in periodontal regeneration. Method: PMN-derived NPRMs were developed to deliver the LXA4-analog to the site of surgery for the purpose of controlling inflammation and promoting tissue and bone growth. A mini-pig-model of chronic periodontitis was surgically created and progressed into chronic periodontal infrabony defects using wire ligatures. Sites (n=16) were treated with reflection of mucoperiosteal flaps, debridement of the periodontal defect and placement of 1) control, 2) NPRM, 3) LXA4 analog and 4) NPRM+L...
Quantitative analysis of tissues and organs can reveal large-scale patterning as well as the impa... more Quantitative analysis of tissues and organs can reveal large-scale patterning as well as the impact of perturbations and aging on biological architecture. Here we develop tools for imaging of single cells in intact organs and computational approaches to assess spatial relationships in 3D. In the mouse ovary, we use nuclear volume of the oocyte to read out quiescence or growth of oocyte-somatic cell units known as follicles. This in-ovary quantification of non-growing follicle dynamics from neonate to adult fits a mathematical function, which corroborates the model of fixed oocyte reserve. Mapping approaches show that radial organization of folliculogenesis established in the newborn ovary is preserved through adulthood. By contrast, inter-follicle clustering increases during aging with different dynamics depending on size. These broadly applicable tools can reveal high dimensional phenotypes and age-related architectural changes in other organs. In the adult mouse pancreas, we find ...
Objectives: The aim of this work was to investigate the activation of NFATc1 (transcription facto... more Objectives: The aim of this work was to investigate the activation of NFATc1 (transcription factor activated in the calcium-calcineurin pathway) in osteoblast-like cells (Saos-2) after exposure to Portland cement (PC). Upon activation by the phosphatase calcineurin, NFATc1 translocates to the nucleus. PC-based endodontic materials have attracted attention recently, because they are able to support bone cell growth and to restore normal mineralization rate in bone defects. However, information on the cellular and molecular responses triggered by PC, mainly calcium signaling, is incomplete. Methods: We determined the dose-response of Saos-2 to PC elute by MTT assay. We next determined NFATc1 subcellular localization in Saos-2 exposed to PC (10mg/mL; 1, 3, 6 and 72h) or PC plus a calcineurin inhibitor (FK506) by confocal microscopy and western blotting analysis. The relative intracellular calcium increase was determined with fluorescent calcium-indicator (Fluo-4 Direct). The expression...
ÐWhen cupric and zinc ions existed at relatively high concentrations (100 ppm each) in the aqueou... more ÐWhen cupric and zinc ions existed at relatively high concentrations (100 ppm each) in the aqueous media, a Na±alginate solution can be directly dispensed into the aqueous media (initial pH: 2.6±5.4) circulating in a loop¯uidized-bed reactor to produce spherical alginate gels in situ that contain both Cu and Zn. An extended Langmuir model for two adsorbates competing for the same type of binding sites was tested against batch absorption data obtained with these gels. Conditional binding stability constants for Cu±alginate and Zn±alginate and binding capacity of the alginate were obtained from the proposed model for each initial pH. Selectivity calculated as the ratio of the stability constant of Cu±alginate to that of Zn±alginate was found to be about 10.
Objective: Bioengineering strategies focus on delivering scaffold materials and growth factors to... more Objective: Bioengineering strategies focus on delivering scaffold materials and growth factors to modulate cellular and tissue responses. However, early innate immune events, such as coagulation and local inflammation, that are crucial for healing have not been the target of therapeutic strategies. The goal of this investigation was to evaluate the potential of nano-proresolving medicines (NPRMs) containing a lipoxin A4 (LXA4) analog that promotes resolution of inflammation for periodontal tissue regeneration. Method: A mini-pig-model of chronic periodontitis was surgically created with a wire ligature. PMN-derived microparticles were isolated and characterized for Annexin 1 expression and ability to activate resolution. Each pig with previously created chronic periodontal infrabony defects was treated with reflection of full thickness mucoperiosteal flaps, complete debridement of the periodontal defect, placement of 1) control, 2) NPRM, 3) LXA4 analog and 4) NPRM+ LXA4analog and wo...
The specificity of monoclonal antibodies represents a potential therapeutic advantage, but their ... more The specificity of monoclonal antibodies represents a potential therapeutic advantage, but their use as single agents in oncology has proven limited to date. The development of antibody-drug conjugates (ADCs) takes advantage of the specificity of the monoclonal antibody and potent cytotoxic effect of chemotherapy, leading to enhanced cytotoxicity in target cells and limiting toxicity to normal tissue. Microtubules represent a validated oncologic target in a range of tumor types, with a number of anti-microtubule targeting cytotoxic drugs approved for cancer use. The systemic use of potent microtubule-binding agents is limited by their effects in normal cells, which leads to toxicity including myelosuppression and peripheral neuropathy. Linking these agents to monoclonal antibodies may limit toxicity to normal tissues and increase drug concentration in target tissues, also allowing the use of more potent agents which would be too toxic to administer in their unbound form. Two such ADCs have been approved for clinical use and many others are in development. Here we review the characteristics of each of the ADC components that have led to efficacious therapies and discuss some of the tubulin inhibitor-based ADCs in development for cancer therapy.
Absolute risk estimation is a preferred approach for assessing fracture risk and treatment decisi... more Absolute risk estimation is a preferred approach for assessing fracture risk and treatment decision making. This study aimed to evaluate and validate the predictive performance of the Garvan Fracture Risk Calculator in a Norwegian cohort. The analysis included 1637 women and 1355 aged 60+ years from the Tromsø study. All incident fragility fractures between 2001 and 2009 were registered. The predicted probabilities of non-vertebral osteoporotic and hip fractures were determined using models with and without BMD. The discrimination and calibration of the models were assessed. Reclassification analysis was used to compare the models performance. The incidence of osteoporotic and hip fracture was 31.5 and 8.6 per 1000 population in women, respectively; in men the corresponding incidence was 12.2 and 5.1. The predicted 5-year and 10-year probability of fractures was consistently higher in the fracture group than the non-fracture group for all models. The 10-year predicted probabilities ...
Fat mass, which is a major component of body weight, is directly related to bone mineral density ... more Fat mass, which is a major component of body weight, is directly related to bone mineral density and reduced fracture risk. It is not known whether abdominal fat is associated with hip fracture. The present study was designed to examine the association between abdominal fat and hip fracture in women and men aged 60+ years. This was a nested case-control study with one fracture case being matched with two controls of the same age. In women 63 cases were matched with 126 controls, and in men 26 cases were matched with 52 controls. Hip fracture was confirmed by X-ray and personal interview. Other measurements included weight, height, body mass index (BMI), abdominal fat, and femoral neck bone density (FNBMD). Conditional logistic regression model was used to analyse data. The odds ratio of hip fracture risk associated with each 10% lower abdominal fat was 1.5 (95% CI, 1.1 to 2.1) in women and 1.2 (95% CI, 0.7 to 2.0) in men. However after adjusting for FNBMD or body weight, the abdomin...
rm's idiosyncratic cost, its exporting sta- tus, and the volatilities of its domestic and ex... more rm's idiosyncratic cost, its exporting sta- tus, and the volatilities of its domestic and export sales. In prior models of trade, production costs for domestic and exports were linear and thus additively separable. We introduce a nonlinear cost function in order to link the domestic and export sales of a rm. This theoretical contribution has two new implications for the ex- porting
The selectivity of the kelp alginate gel for copper compared to cobalt was investigated. When cop... more The selectivity of the kelp alginate gel for copper compared to cobalt was investigated. When copper and cobalt existed at relatively high concentrations (100 ppm each), Na-alginate solution was directly dispensed into the mixed solution circulating in a loop fluidized bed reactor to produce Cu/Co-alginate gels in situ. Two extended Langmuir models were derived and tested against experimental data in this work: Model 1 was a general Langmuir model for two absorbates competing for the same type of binding site. Model 2 was based on the "egg-box" model for gelation of sodium alginate in the presence of divalent metal ions with the assumption that each metal ion would bind two carboxyl groups on neighboring uronate residues that formed the "site". It was found that Model 1 data better and parameters obtained from Model 1 were used to predict the amount of Na-alginate needed to "polish" a cobalt solution containing a trace amount of copper.
Background: Cyproheptadine (CY) is an antihistaminic agent that is commonly used for symptom reli... more Background: Cyproheptadine (CY) is an antihistaminic agent that is commonly used for symptom relief in skin conditions. The most common pattern of cutaneous drug eruption in children is the exanthematous type, with the penicillin family often cited. CY is also an antiserotoninergic agent with the side effect of appetite stimulation and has been used in children with poor feeding and poor weight gain. The Case: We report a case of a 31-month-old male patient seen in the outpatient setting with a diffuse morbilliform rash after use of amoxicillin for right otitis media. The patient was a post-operative congenital heart disease (CHD) patient, actively being treated with CY for feeding difficulties and low weight often seen in the CHD population. Amoxicillin was discontinued, while CY was continued. The patient did not encounter any pruritic symptoms during morbilliform rash, while weight gain of 3.1 kg occurred over a 9 months period, increasing patient from the 10th to 41st percentile...
2 Rowe SP, Gorin MA, Allaf ME et al. PET imaging of prostate-specific membrane antigen in prostat... more 2 Rowe SP, Gorin MA, Allaf ME et al. PET imaging of prostate-specific membrane antigen in prostate cancer: current state of the art and future challenges. Prostate Cancer Prostatic Dis 2016; 19: 223-30 3 Albisinni S, Artigas C, Aoun F et al. Clinical impact of 68 Ga-prostatespecific membrane antigen (PSMA) positron emission tomography/ computed tomography (PET/CT) in patients with prostate cancer with rising prostate-specific antigen after treatment with curative intent: preliminary analysis of a multidisciplinary approach. BJU Int 2017; 120: 197-203 4 van Leeuwen PJ, Stricker P, Hruby G et al. 68 Ga-PSMA has a high detection rate of prostate cancer recurrence outside the prostatic fossa in patients being considered for salvage radiation treatment.
Motor-vehicle crashes are a leading cause of death among children in the United States, and almos... more Motor-vehicle crashes are a leading cause of death among children in the United States, and almost one-fourth of all trips by school-aged children are trips to and from school. This study sought to determine how children (5-18years) travel to and from school and, among those living ≤1mile of school, to explore the role of school bus service eligibility on school travel mode. We used national 2012 survey data to determine prevalence of usual school travel mode, stratified by distance from school. For those living ≤1mile of school, multivariable regression was conducted to assess the association between bus service eligibility and walking or bicycling. Almost half (46.6%) of all children rode in passenger vehicles (PV) to school and 41.8% did so for the trip home. Results were similar among those living ≤1mile (48.1%, PV to school; 41.3%, PV to home). Among those living ≤1mile, 21.9% and 28.4% of children walked or bicycled to and from school, respectively. Ineligibility for school bus service was strongly associated with walking or bicycling to school [adjusted prevalence ratio (aPR: 5.36; p&lt;0.001)] and from school (aPR: 5.36; p&lt;0.001). Regardless of distance from school, passenger vehicles were a common mode of travel. For children who live close to school, the role that school bus service eligibility plays in walking or bicycling deserves further consideration. Given the large proportion of children who use passenger vehicles for school travel, effective interventions can be adopted to increase proper child restraint and seat belt use and reduce crash risks among teen drivers. Better understanding of conditions under which bus service is offered to children who live close to school could inform efforts to improve pedestrian and bicyclist safety for school travel.
Few studies have focused on the bacterial species associated with the deterioration of the dental... more Few studies have focused on the bacterial species associated with the deterioration of the dental and gingival health of children with congenital heart defects (CHD). The aims of this study were (1) to examine the dental plaque of children with CHD in order to quantify bacterial load and altered bacterial composition compared with children without CHD; and (2) to investigate the correlation between the level of caries and gingivitis and dental biofilm bacteria among those children. In this cross-sectional study, participants were children (3-12 years) recruited in Khartoum State, Sudan. A total of 80 CHD cases from the Ahmed Gasim Cardiac Centre and 80 healthy controls from randomly selected schools and kindergartens were included. Participants underwent clinical oral examinations for caries (decayed, missing, and filled teeth indices [DMFT] for primary dentition, and DMFT for permanent dentition), and gingivitis (simplified gingival index [GI]). Pooled dental biofilm samples were o...
Using a robust series of 2511 patients followed for a median time of 9.0 yr, Stewart-Merrill et a... more Using a robust series of 2511 patients followed for a median time of 9.0 yr, Stewart-Merrill et al proposed a novel approach that enables a tailored follow-up strategy following surgical resection of clinically localized renal cell carcinoma (RCC). By means of competing risk models incorporating age, Charlson comorbidity index (CCI), pathologic tumor stage, and recurrence location (abdomen, chest, bone, other), the authors determined the points in time at which the patient's risk of dying from a non-RCC cause exceeded that of recurrence. They found considerable variability in those time points. Among patients with pT1Nx-0 disease who had CCI <1, for example, the risk of non-RCC death began to exceed that of abdominal recurrence at 7 yr for patients aged 50-59 yr, at 2.5 yr for patients aged 60-69 yr, and at 6 mo for patients aged !80 yr. The authors concluded that their competing risks model allows for better prediction and offers an individualized surveillance strategy based on the patient's health status and cancer characteristics. This risk-adapted approach offers the advantage of forgoing unnecessary follow-up when not needed and prolonging it when necessary but not recommended by current guidelines.
Angiogenesis is critical for tumor growth and survival and involves interactions between cancer a... more Angiogenesis is critical for tumor growth and survival and involves interactions between cancer and endothelial cells. Prostate-specific membrane antigen (PSMA/FOLH1) is expressed in the neovasculature of several types of cancer. However, the study of neovascular PSMA expression has been impeded as human umbilical vein endothelial cell (HUVEC) cultures are PSMA-negative and both tumor xenografts and patient-derived xenograft (PDX) models are not known to express PSMA in their vasculature. Therefore, PSMA expression was examined in HUVECs, in vitro and in vivo, and we tested the hypothesis that cancer cell-HUVEC crosstalk could induce the expression of PSMA in HUVECs. Interestingly, conditioned media from several cancer cell lines induced PSMA expression in HUVECs, in vitro, and these lines induced PSMA, in vivo, in a HUVEC co-implantation mouse model. Furthermore, HUVECs in which PSMA expression was induced were able to internalize J591, a monoclonal antibody (mAb) that recognizes a...
In 2010, the Deepwater Horizon (DWH) oil spill adversely impacted many communities along the Gulf... more In 2010, the Deepwater Horizon (DWH) oil spill adversely impacted many communities along the Gulf of Mexico. Effects on Gulf waters, marshes, aquatic life, and fisheries were evident in the following days, months, and years. Through studying affected communities' perceptions regarding the DWH accident, we aim to identify behavioral changes, understand public information sources, and inform dissemination strategies that improve communications from regulatory agencies. Over a three-year period (2012-2015), residents (n = 192) from 7 coastal parishes in southeast Louisiana were surveyed about their perceptions and behaviors before, during, and after the DWH accident. Self-reported consumption of local seafood decreased significantly (50%) during the DWH oil spill but returned to pre-event reported levels by 2015. However, negative seafood quality perceptions remain and have not returned to what were generally positive pre-event levels. Over 30% of study participants trust relatives...
Objective: Uncontrolled host defense mechanisms can significantly impede tissue engineering, rege... more Objective: Uncontrolled host defense mechanisms can significantly impede tissue engineering, regeneration and reconstruction of oral and craniofacial tissues. The anti-inflammatory and pro-resolving actions of lipoxins and resolvins have already been documented in several preclinical models of inflammatory diseases including periodontal disease. The aim of this study was to evaluate the potential of Novel Pro-Resolving-Medicines (NPRMs) containing a lipoxin A4 (LXA4) analog in periodontal regeneration. Method: PMN-derived NPRMs were developed to deliver the LXA4-analog to the site of surgery for the purpose of controlling inflammation and promoting tissue and bone growth. A mini-pig-model of chronic periodontitis was surgically created and progressed into chronic periodontal infrabony defects using wire ligatures. Sites (n=16) were treated with reflection of mucoperiosteal flaps, debridement of the periodontal defect and placement of 1) control, 2) NPRM, 3) LXA4 analog and 4) NPRM+L...
Quantitative analysis of tissues and organs can reveal large-scale patterning as well as the impa... more Quantitative analysis of tissues and organs can reveal large-scale patterning as well as the impact of perturbations and aging on biological architecture. Here we develop tools for imaging of single cells in intact organs and computational approaches to assess spatial relationships in 3D. In the mouse ovary, we use nuclear volume of the oocyte to read out quiescence or growth of oocyte-somatic cell units known as follicles. This in-ovary quantification of non-growing follicle dynamics from neonate to adult fits a mathematical function, which corroborates the model of fixed oocyte reserve. Mapping approaches show that radial organization of folliculogenesis established in the newborn ovary is preserved through adulthood. By contrast, inter-follicle clustering increases during aging with different dynamics depending on size. These broadly applicable tools can reveal high dimensional phenotypes and age-related architectural changes in other organs. In the adult mouse pancreas, we find ...
Objectives: The aim of this work was to investigate the activation of NFATc1 (transcription facto... more Objectives: The aim of this work was to investigate the activation of NFATc1 (transcription factor activated in the calcium-calcineurin pathway) in osteoblast-like cells (Saos-2) after exposure to Portland cement (PC). Upon activation by the phosphatase calcineurin, NFATc1 translocates to the nucleus. PC-based endodontic materials have attracted attention recently, because they are able to support bone cell growth and to restore normal mineralization rate in bone defects. However, information on the cellular and molecular responses triggered by PC, mainly calcium signaling, is incomplete. Methods: We determined the dose-response of Saos-2 to PC elute by MTT assay. We next determined NFATc1 subcellular localization in Saos-2 exposed to PC (10mg/mL; 1, 3, 6 and 72h) or PC plus a calcineurin inhibitor (FK506) by confocal microscopy and western blotting analysis. The relative intracellular calcium increase was determined with fluorescent calcium-indicator (Fluo-4 Direct). The expression...
ÐWhen cupric and zinc ions existed at relatively high concentrations (100 ppm each) in the aqueou... more ÐWhen cupric and zinc ions existed at relatively high concentrations (100 ppm each) in the aqueous media, a Na±alginate solution can be directly dispensed into the aqueous media (initial pH: 2.6±5.4) circulating in a loop¯uidized-bed reactor to produce spherical alginate gels in situ that contain both Cu and Zn. An extended Langmuir model for two adsorbates competing for the same type of binding sites was tested against batch absorption data obtained with these gels. Conditional binding stability constants for Cu±alginate and Zn±alginate and binding capacity of the alginate were obtained from the proposed model for each initial pH. Selectivity calculated as the ratio of the stability constant of Cu±alginate to that of Zn±alginate was found to be about 10.
Objective: Bioengineering strategies focus on delivering scaffold materials and growth factors to... more Objective: Bioengineering strategies focus on delivering scaffold materials and growth factors to modulate cellular and tissue responses. However, early innate immune events, such as coagulation and local inflammation, that are crucial for healing have not been the target of therapeutic strategies. The goal of this investigation was to evaluate the potential of nano-proresolving medicines (NPRMs) containing a lipoxin A4 (LXA4) analog that promotes resolution of inflammation for periodontal tissue regeneration. Method: A mini-pig-model of chronic periodontitis was surgically created with a wire ligature. PMN-derived microparticles were isolated and characterized for Annexin 1 expression and ability to activate resolution. Each pig with previously created chronic periodontal infrabony defects was treated with reflection of full thickness mucoperiosteal flaps, complete debridement of the periodontal defect, placement of 1) control, 2) NPRM, 3) LXA4 analog and 4) NPRM+ LXA4analog and wo...
The specificity of monoclonal antibodies represents a potential therapeutic advantage, but their ... more The specificity of monoclonal antibodies represents a potential therapeutic advantage, but their use as single agents in oncology has proven limited to date. The development of antibody-drug conjugates (ADCs) takes advantage of the specificity of the monoclonal antibody and potent cytotoxic effect of chemotherapy, leading to enhanced cytotoxicity in target cells and limiting toxicity to normal tissue. Microtubules represent a validated oncologic target in a range of tumor types, with a number of anti-microtubule targeting cytotoxic drugs approved for cancer use. The systemic use of potent microtubule-binding agents is limited by their effects in normal cells, which leads to toxicity including myelosuppression and peripheral neuropathy. Linking these agents to monoclonal antibodies may limit toxicity to normal tissues and increase drug concentration in target tissues, also allowing the use of more potent agents which would be too toxic to administer in their unbound form. Two such ADCs have been approved for clinical use and many others are in development. Here we review the characteristics of each of the ADC components that have led to efficacious therapies and discuss some of the tubulin inhibitor-based ADCs in development for cancer therapy.
Absolute risk estimation is a preferred approach for assessing fracture risk and treatment decisi... more Absolute risk estimation is a preferred approach for assessing fracture risk and treatment decision making. This study aimed to evaluate and validate the predictive performance of the Garvan Fracture Risk Calculator in a Norwegian cohort. The analysis included 1637 women and 1355 aged 60+ years from the Tromsø study. All incident fragility fractures between 2001 and 2009 were registered. The predicted probabilities of non-vertebral osteoporotic and hip fractures were determined using models with and without BMD. The discrimination and calibration of the models were assessed. Reclassification analysis was used to compare the models performance. The incidence of osteoporotic and hip fracture was 31.5 and 8.6 per 1000 population in women, respectively; in men the corresponding incidence was 12.2 and 5.1. The predicted 5-year and 10-year probability of fractures was consistently higher in the fracture group than the non-fracture group for all models. The 10-year predicted probabilities ...
Fat mass, which is a major component of body weight, is directly related to bone mineral density ... more Fat mass, which is a major component of body weight, is directly related to bone mineral density and reduced fracture risk. It is not known whether abdominal fat is associated with hip fracture. The present study was designed to examine the association between abdominal fat and hip fracture in women and men aged 60+ years. This was a nested case-control study with one fracture case being matched with two controls of the same age. In women 63 cases were matched with 126 controls, and in men 26 cases were matched with 52 controls. Hip fracture was confirmed by X-ray and personal interview. Other measurements included weight, height, body mass index (BMI), abdominal fat, and femoral neck bone density (FNBMD). Conditional logistic regression model was used to analyse data. The odds ratio of hip fracture risk associated with each 10% lower abdominal fat was 1.5 (95% CI, 1.1 to 2.1) in women and 1.2 (95% CI, 0.7 to 2.0) in men. However after adjusting for FNBMD or body weight, the abdomin...
rm's idiosyncratic cost, its exporting sta- tus, and the volatilities of its domestic and ex... more rm's idiosyncratic cost, its exporting sta- tus, and the volatilities of its domestic and export sales. In prior models of trade, production costs for domestic and exports were linear and thus additively separable. We introduce a nonlinear cost function in order to link the domestic and export sales of a rm. This theoretical contribution has two new implications for the ex- porting
The selectivity of the kelp alginate gel for copper compared to cobalt was investigated. When cop... more The selectivity of the kelp alginate gel for copper compared to cobalt was investigated. When copper and cobalt existed at relatively high concentrations (100 ppm each), Na-alginate solution was directly dispensed into the mixed solution circulating in a loop fluidized bed reactor to produce Cu/Co-alginate gels in situ. Two extended Langmuir models were derived and tested against experimental data in this work: Model 1 was a general Langmuir model for two absorbates competing for the same type of binding site. Model 2 was based on the "egg-box" model for gelation of sodium alginate in the presence of divalent metal ions with the assumption that each metal ion would bind two carboxyl groups on neighboring uronate residues that formed the "site". It was found that Model 1 data better and parameters obtained from Model 1 were used to predict the amount of Na-alginate needed to "polish" a cobalt solution containing a trace amount of copper.
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Papers by Daniel Nguyen