RESUMO
Traumatic brain injury (TBI) results in activated microglia. Activated microglia can be measured in vivo by using positron emission topography (PET) ligand peripheral benzodiazepine receptor standardized uptake values (PBR28suv). Cell based therapies have utilized autologous bone marrow mononuclear cells (BMMNCs) to attenuate activated microglia after TBI. This study aims to utilize in vivo PBR28suv to assess the efficacy of BMMNCs therapy after TBI. Seventy-two hours after CCI injury, BMMNCs were harvested from the tibia and injected via tail-vein at 74 h after injury at a concentration of 2 million cells per kilogram of body weight. There were three groups of rats: Sham, CCI-alone and CCI-BMMNCs (AUTO). One hundred twenty days after injury, rodents were imaged with PBR28 and their cognitive behavior assessed utilizing the Morris Water Maze. Subsequent ex vivo analysis included brain volume and immunohistochemistry. BMMNCs therapy attenuated PBR28suv in comparison to CCI alone and it improved spatial learning as measured by the Morris Water Maze. Ex vivo analysis demonstrated preservation of brain volume, a decrease in amoeboid-shaped microglia in the dentate gyrus and an increase in the ratio of ramified to amoeboid microglia in the thalamus. PBR28suv is a viable option to measure efficacy of BMMNCs therapy after TBI.
Assuntos
Lesões Encefálicas Traumáticas , Microglia , Animais , Ratos , Medula Óssea , Elétrons , Lesões Encefálicas Traumáticas/diagnóstico por imagem , Lesões Encefálicas Traumáticas/terapia , Tomografia por Emissão de PósitronsRESUMO
BACKGROUND: A number of modifiable risk factors have been designated as being causally related to cancer development. We aimed to estimate the percentage of incident cancer cases diagnosed in persons aged ≥25 years in Texas in 2015, overall and by race/ethnicity, that were attributable to these modifiable risk factors. METHODS: We calculated population attributable fractions (PAFs) for cancers attributable to thirteen modifiable risk factors using prevalence data from the Texas Behavioral Risk Factor Surveillance System and the National Health and Nutrition Examination Survey, as well as relative risks estimates from prior studies and cancer incidence data from the Texas Cancer Registry. RESULTS: Overall, 32.3% of all incident cancers (N = 33,416) in 2015 were attributable to modifiable risk factors. Men (35.1%) had a numerically higher overall PAF than women (29.5%). Tobacco smoking caused the highest proportion of cancers (18.4%), followed by overweight and obesity (6.6%) and excess alcohol consumption (2.9%). Non-Hispanic Blacks had a numerically higher overall PAF (36.8%) than non-Hispanic Whites (31.9%) and Hispanics (31.7%). Further, non-Hispanic Blacks had the highest combined PAFs for 85% of cancer sites analyzed, including lung/bronchus and mouth/pharynx/larynx. CONCLUSION: Modifiable risk factors cause about one third of cancers in Texas. Non-Hispanic Blacks are especially affected by an excessive preventable cancer burden.
Assuntos
Etnicidade , Neoplasias , Feminino , Humanos , Incidência , Masculino , Neoplasias/epidemiologia , Neoplasias/etiologia , Inquéritos Nutricionais , Prevalência , Fatores de Risco , Texas/epidemiologiaRESUMO
OBJECTIVES: Tobacco smoking is classified as carcinogenic to humans (International Agency for Research on Cancer Group 1). We aimed to estimate the percentage and number of incident cancer cases diagnosed in Texas in 2015 that were attributable to tobacco smoking, and we examined differences in the proportions of smoking-attributable cancers between the major racial/ethnic subgroups of the population. METHODS: We calculated population-attributable fractions for cancers attributable to tobacco smoking using prevalence data from the Texas Behavioral Risk Factor Surveillance System and relative risks associated with smoking status from pooled analyses of cohort studies or meta-analyses. Cancer incidence data were collected from the Texas Cancer Registry. RESULTS: We estimated that 19,000 excess cancer cases or 18.4% of all cancers diagnosed in 2015 in Texans aged ≥ 25 years were caused by tobacco smoking. Males had a higher overall proportion of cancers attributable to tobacco smoking than females (male, 23.3%, 11,993 excess cases; female, 13.5%, 7,006 cases). Approximately 20% of cancer cases in non-Hispanic Whites and non-Hispanic Blacks were attributable to tobacco smoking compared to 12.8% among Hispanics. CONCLUSIONS: Despite ongoing public health campaigns combatting tobacco use, this preventable behavior still contributes significantly to cancer incidence in Texas. Racial/ethnic differences in smoking prevalence and smoking-attributable cancer incidence should be considered when designing cancer prevention programs.
Assuntos
Etnicidade/estatística & dados numéricos , Neoplasias/etnologia , Grupos Raciais/estatística & dados numéricos , Fumar Tabaco/etnologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Disparidades nos Níveis de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/etiologia , Neoplasias/prevenção & controle , Sistema de Registros , Fatores de Risco , Texas/epidemiologia , Fumar Tabaco/efeitos adversos , Adulto JovemRESUMO
We estimated the percentage and number of all incident cancer cases diagnosed in Texas in 2015 that were attributable to inadequate diet and examined for racial/ethnic differences. We calculated population attributable fractions for cancers with a causal relationship with red and processed meat consumption, insufficient fiber intake, and insufficient calcium intake, using prevalence estimates from the National Health and Nutrition Examination Survey and relative risk estimates from the World Cancer Research Fund/American Institute for Cancer Research 2018 Third Expert Report. Overall, 3.3% of all new cancers (3,428 cases) diagnosed in Texas in 2015 were attributable to inadequate diet. More diet-associated cancers were diagnosed in men (3.8%) than women (2.9%). Insufficient fiber intake (1.2%) contributed more cancers than processed meat consumption (1.0%), insufficient calcium intake (0.8%), and red meat consumption (0.4%). Non-Hispanic Blacks (4.4%) had a higher proportion of cancers attributable to inadequate diet than Hispanics (3.7%) and non-Hispanic Whites (3.1%). Considering only colorectal cancers, inadequate diet caused 39.6% of cases in non-Hispanic Blacks, compared to 33.6% in non-Hispanic Whites and 33.4% in Hispanics. Inadequate diet serves as an important but preventable source of cancer. In general, and for minority populations specifically, cancer prevention programs should continue to advocate for universal compliance with recommended dietary guidelines.
RESUMO
Traumatic brain injury (TBI) is a chronic, life threatening injury for which few effective interventions are available. Evidence in animal models suggests un-checked immune activation may contribute to the pathophysiology. Changes in regional density of active brain microglia can be quantified in vivo with positron emission topography (PET) with the relatively selective radiotracer, peripheral benzodiazepine receptor 28 (11 C-PBR28). Phenotypic assessment (activated vs resting) can subsequently be assessed (ex vivo) using morphological techniques. To elucidate the mechanistic contribution of immune cells in due to TBI, we employed a hybrid approach involving both in vivo (11 C-PBR28 PET) and ex vivo (morphology) to elucidate the role of immune cells in a controlled cortical impact (CCI), a rodent model for TBI. Density of activated brain microglia/macrophages was quantified 120 hours after injury using the standardized uptake value (SUV) approach. Ex vivo morphological analysis from specific brain regions using IBA-1 antibodies differentiated ramified (resting) from amoeboid (activated) immune cells. Additional immunostaining of PBRs facilitated co-localization of PBRs with IBA-1 staining to further validate PET data. Injured animals displayed greater PBR28suv when compared to sham animals. Immunohistochemistry demonstrated elevated density of amoeboid microglia/macrophages in the ipsilateral dentate gyrus, corpus callosum, thalami and injury penumbra of injured animals compared to sham animals. PBR co-stained with amoeboid microglia/macrophages in the injury penumbra and not with astrocytes. These data suggest the technologies evaluated may serve as bio-signatures of neuroinflammation following severe brain injury in small animals, potentially enabling in vivo tracking of neuroinflammation following TBI and cellular-based therapies.
Assuntos
Lesões Encefálicas Traumáticas/diagnóstico por imagem , Lesões Encefálicas Traumáticas/metabolismo , Modelos Animais de Doenças , Tomografia por Emissão de Pósitrons/métodos , Pirimidinas/metabolismo , Receptores de GABA-A/metabolismo , Animais , Masculino , Ratos , Ratos Sprague-Dawley , RoedoresRESUMO
OBJECTIVE: The International Agency for Research on Cancer has classified 13 infectious agents as carcinogenic or probably carcinogenic to humans. We aimed to estimate the percentage (ie, population-attributable fraction) and number of incident cancer cases in Texas in 2015 that were attributable to oncogenic infections, overall and by race/ethnicity. METHODS: We calculated population-attributable fractions for cancers attributable to human papillomavirus (HPV), Helicobacter pylori, hepatitis C virus (HCV), hepatitis B virus (HBV), and human herpesvirus 8 (HHV-8) infections using prevalence estimates from National Health and Nutrition Examination Survey laboratory data and relative risks associated with infection from previous epidemiological studies. The Texas Cancer Registry provided cancer incidence data. RESULTS: We estimated that 3603 excess cancer cases, or 3.5% of all cancers diagnosed in 2015, among adults aged ≥25 in Texas were attributable to oncogenic infections. Hispanic adults had the highest proportion of cancer cases attributable to infections (5.6%), followed by non-Hispanic Black (5.4%) and non-Hispanic White (2.3%) adults. HPV infection caused the highest proportion of all cancer cases (1.8%) compared with other oncogenic infections (HCV, 0.8%; H pylori, 0.5%; HBV, 0.3%; HHV-8, 0.1%). Hispanic adults had the highest proportions of all cancers caused by HPV infection (2.6%) and H pylori (1.1%), and non-Hispanic Black adults had the highest proportions of all cancers caused by HCV infection (1.7%), HBV infection (0.7%), and HHV-8 (0.3%). CONCLUSION: Preventable oncogenic infections contribute to cancer incidence in Texas and may affect racial/ethnic minority groups disproportionately. Infection control and prevention should be stressed as an important component of cancer prevention.
Assuntos
Etnicidade/estatística & dados numéricos , Infecções por Helicobacter/complicações , Grupos Minoritários/estatística & dados numéricos , Neoplasias/etnologia , Neoplasias/etiologia , Viroses/complicações , Adulto , Idoso , Feminino , Helicobacter pylori , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos Nutricionais , Texas/epidemiologiaRESUMO
BACKGROUND: According to the 2018 Third Expert Report from the World Cancer Research Fund/American Institute for Cancer Research, there is strong evidence that physical activity of all types and intensities protects against colon, endometrial and breast cancers. We aimed to estimate the percentage and number of incident cancer cases diagnosed in Texas in 2015 that were attributable to insufficient physical activity, and we examined for differences across racial/ethnic subgroups to reveal important causes of and potential avenues for reductions to cancer health disparities. METHODS: We calculated population attributable fractions for cancers attributable to insufficient physical activity using prevalence data from the Texas Behavioral Risk Factor Surveillance System and relative risk estimates associated with insufficient physical activity from prior studies. Cancer incidence data were gathered from the Texas Cancer Registry. RESULTS: Overall, approximately 2.0% of all new cancers or 2094 excess cancer cases diagnosed in 2015 in Texans aged ≥25 years were attributable to insufficient physical activity, with more cancers in women (3.2%) than in men (0.8%). Of all cancer sites, the highest population attributable fraction for insufficient physical activity was observed for endometrial cancers (21.7% compared with 12.7% for colon cancers, 10.9% for premenopausal breast cancers and 2.0% for postmenopausal breast cancers). Hispanics (2.6%) and non-Hispanic blacks (2.5%) had higher proportions of cancers attributable to insufficient physical activity than non-Hispanic whites (1.8%). CONCLUSIONS: Public health programmes should stress physical activity as a means of cancer prevention, especially among minority groups, who may have disproportionately higher percentages of cancers attributable to insufficient physical activity.
RESUMO
BACKGROUND: The United States has large regional variation in primary prevention campaigns for skin cancer. We collected data from all 50 states to examine changes in melanoma incidence and performed age-period-cohort analyses to describe the simultaneous effects of age, period, and cohort on incidence rates. METHODS: Annual melanoma incidence rates for non-Hispanic whites from 2001 to 2015 were extracted from the US Cancer Statistics registry. Secular trends were examined overall and by sex and state. We used joinpoint regression to compute annual percent change and average annual percent change and corresponding 95% confidence intervals (CIs). We also analyzed incidence trends by 5-year age group and birth cohort using incidence rate ratios and age-period-cohort modeling. RESULTS: Melanoma incidence increased from 20.7 per 100 000 (95% CI = 20.5 to 20.9) in 2001 to 28.2 per 100 000 (95% CI = 28.0 to 28.5) in 2015, increasing by 3.90% (95% CI = 2.36% to 5.48%) annually between 2001 and 2005 and 1.68% (95% CI = 1.37% to 1.99%) annually from 2005 through 2015. The average annual percent change in melanoma incidence rates were similar for men (2.34%, 95% CI = 1.91 to 2.78) and women (2.25%, 95% CI = 1.60 to 2.91). Age-specific relative risk by birth cohort increased from circa 1921 to 1981 before decreasing. Compared with adults born circa 1956, those born circa 1991 had lower melanoma risk (incidence rate ratio = 0.85; 95% CI = 0.77 to 0.94). Geographic variation was observed; some states still have melanoma rates trending upwards in all birth cohorts. CONCLUSIONS: The continued increase in melanoma incidence among non-Hispanic whites, particularly in states where rates continue to rise among recent and current birth cohorts, underscores the need for increased public health campaigns aimed at reducing sun exposure.
Assuntos
Melanoma/epidemiologia , Neoplasias Cutâneas/epidemiologia , População Branca/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Incidência , Masculino , Melanoma/etnologia , Pessoa de Meia-Idade , Sistema de Registros , Neoplasias Cutâneas/etnologia , Estados Unidos/epidemiologia , Adulto JovemRESUMO
Alcohol consumption, especially at levels above 3 drinks/day, causes eight different types of cancer. We aimed to estimate the percentage and number of incident cancer cases diagnosed in Texas in 2015 that were attributable to alcohol consumption. We further examined for differences in these estimates across major population racial/ethnic subgroups. We calculated population-attributable fractions for cancers attributable to alcohol consumption using prevalence estimates of alcohol consumption from the Texas Behavioral Risk Factor Surveillance System and relative risks associated with alcohol consumption from the third World Cancer Research Fund/American Institute for Cancer Research expert report. Cancer incidence data were retrieved from the Texas Cancer Registry. We estimated 2.9% of all cancers or 2974 excess cancer cases diagnosed in 2015 in Texans aged ≥25 years were attributable to alcohol consumption. Non-Hispanic Blacks (2.2%) had the lowest proportion of alcohol-attributable cancers. Despite Hispanics having the highest percent of non-consumption of alcohol (65.3%, compared with 45.5% of non-Hispanic Whites), Hispanics had a slightly higher proportion of alcohol-attributable cancers than non-Hispanic Whites (3.0% and 2.7%, respectively). Alcohol consumption is an important target for intervention by public health programs aimed toward addressing cancer prevention. Differences in alcohol-attributable cancer burden among racial/ethnic subgroups should be acknowledged to provide appropriately tailored prevention recommendations.
Assuntos
Consumo de Bebidas Alcoólicas/epidemiologia , Etnicidade/estatística & dados numéricos , Neoplasias/epidemiologia , Grupos Raciais/estatística & dados numéricos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Consumo de Bebidas Alcoólicas/efeitos adversos , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Neoplasias/induzido quimicamente , Prevalência , Sistema de Registros , Fatores de Risco , Texas/epidemiologia , Adulto JovemRESUMO
BACKGROUND: CACNA1A variants have been described in several disorders that encompass a wide range of neurologic phenotypes, including hemiplegic migraine, ataxia, cognitive delay, and epilepsy. To date, ischemic stroke caused by a CACNA1A variant has only been reported once in the literature. METHODS: We describe a 4-year-old female with recurrent ischemic strokes beginning at 6 weeks of age, intractable epilepsy, and significant global developmental delay. Exome sequencing (ES) was completed for her evaluation. RESULTS: We found a novel de novo, likely pathogenic variant, p.Leu1692Gln in CACNA1A by ES. The substitution affects a leucine residue that is highly conserved in species from fish to primates. CONCLUSION: We present the second case of recurrent ischemic strokes in a patient with CACNA1A mutation. Our findings expand the phenotypic heterogeneity related to Cav 2.1 (P/Q-type) calcium channel dysfunction and suggest consideration of CACNA1A disorder in evaluation of pediatric strokes.