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1.
MMWR Morb Mortal Wkly Rep ; 73(12): 265-270, 2024 Mar 28.
Article in English | MEDLINE | ID: mdl-38547024

ABSTRACT

After 27 years of declining U.S. tuberculosis (TB) case counts, the number of TB cases declined considerably in 2020, coinciding with the COVID-19 pandemic. For this analysis, TB case counts were obtained from the National TB Surveillance System. U.S. Census Bureau population estimates were used to calculate rates overall, by jurisdiction, birth origin, race and ethnicity, and age group. Since 2020, TB case counts and rates have increased each year. During 2023, a total of 9,615 TB cases were provisionally reported by the 50 U.S. states and the District of Columbia (DC), representing an increase of 1,295 cases (16%) as compared with 2022. The rate in 2023 (2.9 per 100,000 persons) also increased compared with that in 2022 (2.5). Forty states and DC reported increases in 2023 in both case counts and rates. National case counts increased among all age groups and among both U.S.-born and non-U.S.-born persons. Although TB incidence in the United States is among the lowest in the world and most U.S. residents are at minimal risk, TB continues to cause substantial global morbidity and mortality. This postpandemic increase in U.S. cases highlights the importance of continuing to engage communities with higher TB rates and their medical providers in TB elimination efforts and strengthening the capacity in public health programs to carry out critical disease control and prevention strategies.


Subject(s)
Population Surveillance , Tuberculosis , Humans , United States/epidemiology , Pandemics , Morbidity , Tuberculosis/prevention & control , District of Columbia
2.
Emerg Infect Dis ; 29(10): 2016-2023, 2023 10.
Article in English | MEDLINE | ID: mdl-37647628

ABSTRACT

Little is known about co-occurring tuberculosis (TB) and COVID-19 in low TB incidence settings. We obtained a cross-section of 333 persons in the United States co-diagnosed with TB and COVID-19 within 180 days and compared them to 4,433 persons with TB only in 2020 and 18,898 persons with TB during 2017‒2019. Across both comparison groups, a higher proportion of persons with TB-COVID-19 were Hispanic, were long-term care facility residents, and had diabetes. When adjusted for age, underlying conditions, and TB severity, COVID-19 co-infection was not statistically associated with death compared with TB infection only in 2020 (adjusted prevalence ratio 1.0 [95% CI 0.8‒1.4]). Among TB-COVID-19 patients, death was associated with a shorter interval between TB and COVID-19 diagnoses, older age, and being immunocompromised (non-HIV). TB-COVID-19 deaths in the United States appear to be concentrated in subgroups sharing characteristics known to increase risk for death from either disease alone.


Subject(s)
COVID-19 , Tuberculosis , Humans , COVID-19/mortality , Cross-Sectional Studies , Tuberculosis/mortality , United States/epidemiology
3.
MMWR Morb Mortal Wkly Rep ; 72(12): 297-303, 2023 Mar 24.
Article in English | MEDLINE | ID: mdl-36952282

ABSTRACT

Incidence of reported tuberculosis (TB) decreased gradually in the United States during 1993-2019, reaching 2.7 cases per 100,000 persons in 2019. Incidence substantially declined in 2020 to 2.2, coinciding with the COVID-19 pandemic (1). Proposed explanations for the decline include delayed or missed TB diagnoses, changes in migration and travel, and mortality among persons susceptible to TB reactivation (1). Disparities (e.g., by race and ethnicity) in TB incidence have been described (2). During 2021, TB incidence partially rebounded (to 2.4) but remained substantially below that during prepandemic years, raising concerns about ongoing delayed diagnoses (1). During 2022, the 50 U.S. states and the District of Columbia (DC) provisionally reported 8,300 TB cases to the National Tuberculosis Surveillance System. TB incidence was calculated using midyear population estimates and stratified by birth origin and by race and ethnicity. During 2022, TB incidence increased slightly to 2.5 although it remained lower than during prepandemic years.* Compared with that in 2021, TB epidemiology in 2022 was characterized by more cases among non-U.S.-born persons newly arrived in the United States; higher TB incidence among non-Hispanic American Indian or Alaska Native (AI/AN) and non-Hispanic Native Hawaiian or other Pacific Islander (NH/OPI) persons and persons aged ≤4 and 15-24 years; and slightly lower incidence among persons aged ≥65 years. TB incidence appears to be returning to prepandemic levels. TB disparities persist; addressing these disparities requires timely TB diagnosis and treatment to interrupt transmission and prevention of TB through treatment of latent TB infection (LTBI).


Subject(s)
COVID-19 , Tuberculosis , United States/epidemiology , Humans , Pandemics , COVID-19/epidemiology , Tuberculosis/prevention & control , Ethnicity , District of Columbia , Incidence
4.
MMWR Morb Mortal Wkly Rep ; 71(12): 441-446, 2022 Mar 25.
Article in English | MEDLINE | ID: mdl-35324877

ABSTRACT

During 1993-2019, the incidence of tuberculosis (TB) in the United States decreased steadily; however, during the later years of that period the annual rate of decline slowed (1) until 2020 when a substantial decline (19.9%) was observed. This sharp decrease in TB incidence might have been related to multiple factors coinciding with the COVID-19 pandemic, including delayed or missed TB diagnoses or a true reduction in TB incidence related to pandemic mitigation efforts and changes in immigration and travel (2). During 2021, a total of 7,860 TB cases were provisionally reported to CDC's National Tuberculosis Surveillance System (NTSS) by the 50 U.S. states and the District of Columbia (DC). National incidence of reported TB (cases per 100,000 persons) rose 9.4% during 2021 (2.37) compared with that in 2020 (2.16) but remained 12.6% lower than the rate during 2019 (2.71).* During 2021, TB incidence increased among both U.S.-born and non-U.S.-born persons. The increased TB incidence observed during 2021 compared with 2020 might be partially explained by delayed diagnosis of cases in persons with symptom onset during 2020; however, the continued, substantial reduction from prepandemic levels raises concern for ongoing underdiagnosis. TB control and prevention services, including early diagnosis and complete treatment of TB and latent TB infection, should be maintained and TB awareness promoted to achieve elimination in the United States.


Subject(s)
Tuberculosis/epidemiology , COVID-19 , Humans , Incidence , United States/epidemiology
5.
MMWR Morb Mortal Wkly Rep ; 70(12): 409-414, 2021 Mar 26.
Article in English | MEDLINE | ID: mdl-33764959

ABSTRACT

Tuberculosis (TB) disease incidence has decreased steadily since 1993 (1), a result of decades of work by local TB programs to detect, treat, and prevent TB disease and transmission. During 2020, a total of 7,163 TB cases were provisionally reported to CDC's National Tuberculosis Surveillance System (NTSS) by the 50 U.S. states and the District of Columbia (DC), a relative reduction of 20%, compared with the number of cases reported during 2019.* TB incidence per 100,000 persons was 2.2 during 2020, compared with 2.7 during 2019. Since 2010, TB incidence has decreased by an average of 2%-3% annually (1). Pandemic mitigation efforts and reduced travel might have contributed to the reported decrease. The magnitude and breadth of the decrease suggest potentially missed or delayed TB diagnoses. Health care providers should consider TB disease when evaluating patients with signs and symptoms consistent with TB (e.g., cough of >2 weeks in duration, unintentional weight loss, and hemoptysis), especially when diagnostic tests are negative for SARS-CoV-2, the virus that causes COVID-19. In addition, members of the public should be encouraged to follow up with their health care providers for any respiratory illness that persists or returns after initial treatment. The steep, unexpected decline in TB cases raises concerns of missed cases, and further work is in progress to better understand factors associated with the decline.


Subject(s)
Population Surveillance , Tuberculosis/epidemiology , Adolescent , Adult , Aged , COVID-19 , Centers for Disease Control and Prevention, U.S. , Child , Child, Preschool , Emigrants and Immigrants/statistics & numerical data , Ethnicity/statistics & numerical data , Humans , Incidence , Middle Aged , Racial Groups/statistics & numerical data , Tuberculosis/ethnology , United States/epidemiology , Young Adult
6.
Genes Dev ; 27(13): 1447-61, 2013 Jul 01.
Article in English | MEDLINE | ID: mdl-23824538

ABSTRACT

Macroautophagy (autophagy hereafter) degrades and recycles proteins and organelles to support metabolism and survival in starvation. Oncogenic Ras up-regulates autophagy, and Ras-transformed cell lines require autophagy for mitochondrial function, stress survival, and engrafted tumor growth. Here, the essential autophagy gene autophagy-related-7 (atg7) was deleted concurrently with K-ras(G12D) activation in mouse models for non-small-cell lung cancer (NSCLC). atg7-deficient tumors accumulated dysfunctional mitochondria and prematurely induced p53 and proliferative arrest, which reduced tumor burden that was partly relieved by p53 deletion. atg7 loss altered tumor fate from adenomas and carcinomas to oncocytomas-rare, predominantly benign tumors characterized by the accumulation of defective mitochondria. Surprisingly, lipid accumulation occurred in atg7-deficient tumors only when p53 was deleted. atg7- and p53-deficient tumor-derived cell lines (TDCLs) had compromised starvation survival and formed lipidic cysts instead of tumors, suggesting defective utilization of lipid stores. atg7 deficiency reduced fatty acid oxidation (FAO) and increased sensitivity to FAO inhibition, indicating that with p53 loss, Ras-driven tumors require autophagy for mitochondrial function and lipid catabolism. Thus, autophagy is required for carcinoma fate, and autophagy defects may be a molecular basis for the occurrence of oncocytomas. Moreover, cancers require autophagy for distinct roles in metabolism that are oncogene- and tumor suppressor gene-specific.


Subject(s)
Adenoma, Oxyphilic/physiopathology , Autophagy , Carcinoma, Non-Small-Cell Lung/physiopathology , Genes, ras/physiology , Lipid Metabolism , Lung Neoplasms/physiopathology , Animals , Cell Line, Tumor , Gene Deletion , Gene Expression Regulation, Neoplastic , Genes, p53/genetics , Homeostasis , Longevity/genetics , Mice , Mitochondria/pathology , Tumor Cells, Cultured
7.
MMWR Morb Mortal Wkly Rep ; 69(11): 286-289, 2020 Mar 20.
Article in English | MEDLINE | ID: mdl-32191684

ABSTRACT

Since 1989, the United States has pursued a goal of eliminating tuberculosis (TB) through a strategy of rapidly identifying and treating cases and evaluating exposed contacts to limit secondary cases resulting from recent TB transmission (1). This strategy has been highly effective in reducing U.S. TB incidence (2), but the pace of decline has significantly slowed in recent years (2.2% average annual decline during 2012-2017 compared with 6.7% during 2007-2012) (3). For this report, provisional 2019 data reported to CDC's National Tuberculosis Surveillance System were analyzed to determine TB incidence overall and for selected subpopulations and these results were compared with those from previous years. During 2019, a total of 8,920 new cases were provisionally reported in the United States, representing a 1.1% decrease from 2018.* TB incidence decreased to 2.7 cases per 100,000 persons, a 1.6% decrease from 2018. Non-U.S.-born persons had a TB rate 15.5 times greater than the rate among U.S.-born persons. The U.S. TB case count and rate are the lowest ever reported, but the pace of decline remains slow. In recent years, approximately 80% of U.S. TB cases have been attributed to reactivation of latent TB infection (LTBI) acquired years in the past, often outside the United States (2). An expanded TB elimination strategy for this new decade should leverage existing health care resources, including primary care providers, to identify and treat persons with LTBI, without diverting public health resources from the continued need to limit TB transmission within the United States. Partnerships with health care providers, including private providers, are essential for this strategy's success.


Subject(s)
Disease Eradication , Population Surveillance , Tuberculosis/epidemiology , Tuberculosis/prevention & control , Adult , Centers for Disease Control and Prevention, U.S. , Emigrants and Immigrants/statistics & numerical data , Ethnicity/statistics & numerical data , Goals , Humans , Incidence , Tuberculosis/ethnology , United States/epidemiology
8.
MMWR Morb Mortal Wkly Rep ; 69(39): 1410-1415, 2020 Oct 02.
Article in English | MEDLINE | ID: mdl-33001869

ABSTRACT

Approximately 56 million school-aged children (aged 5-17 years) resumed education in the United States in fall 2020.* Analysis of demographic characteristics, underlying conditions, clinical outcomes, and trends in weekly coronavirus disease 2019 (COVID-19) incidence during March 1-September 19, 2020 among 277,285 laboratory-confirmed cases in school-aged children in the United States might inform decisions about in-person learning and the timing and scaling of community mitigation measures. During May-September 2020, average weekly incidence (cases per 100,000 children) among adolescents aged 12-17 years (37.4) was approximately twice that of children aged 5-11 years (19.0). In addition, among school-aged children, COVID-19 indicators peaked during July 2020: weekly percentage of positive SARS-CoV-2 test results increased from 10% on May 31 to 14% on July 5; SARS-CoV-2 test volume increased from 100,081 tests on May 31 to 322,227 on July 12, and COVID-19 incidence increased from 13.8 per 100,000 on May 31 to 37.9 on July 19. During July and August, test volume and incidence decreased then plateaued; incidence decreased further during early September and might be increasing. Percentage of positive test results decreased during August and plateaued during September. Underlying conditions were more common among school-aged children with severe outcomes related to COVID-19: among school-aged children who were hospitalized, admitted to an intensive care unit (ICU), or who died, 16%, 27%, and 28%, respectively, had at least one underlying medical condition. Schools and communities can implement multiple, concurrent mitigation strategies and tailor communications to promote mitigation strategies to prevent COVID-19 spread. These results can provide a baseline for monitoring trends and evaluating mitigation strategies.


Subject(s)
Coronavirus Infections/epidemiology , Coronavirus Infections/therapy , Pneumonia, Viral/epidemiology , Pneumonia, Viral/therapy , Adolescent , COVID-19 , COVID-19 Testing , Child , Child, Preschool , Chronic Disease/epidemiology , Clinical Laboratory Techniques/statistics & numerical data , Coronavirus Infections/diagnosis , Coronavirus Infections/mortality , Female , Hospitalization/statistics & numerical data , Humans , Incidence , Male , Pandemics , Pneumonia, Viral/mortality , Treatment Outcome , United States/epidemiology
9.
MMWR Morb Mortal Wkly Rep ; 67(11): 317-323, 2018 Mar 23.
Article in English | MEDLINE | ID: mdl-29565838

ABSTRACT

In 2017, a total of 9,093 new cases of tuberculosis (TB) were provisionally* reported in the United States, representing an incidence rate of 2.8 cases per 100,000 population. The case count decreased by 1.8% from 2016 to 2017, and the rate declined by 2.5% over the same period. These decreases are consistent with the slight decline in TB seen over the past several years (1). This report summarizes provisional TB surveillance data reported to CDC's National Tuberculosis Surveillance System for 2017 and in the last decade. The rate of TB among non-U.S.-born persons in 2017 was 15 times the rate among U.S.-born persons. Among non-U.S.-born persons, the highest TB rate among all racial/ethnic groups was among Asians (27.0 per 100,000 persons), followed by non-Hispanic blacks (blacks; 22.0). Among U.S.-born persons, most TB cases were reported among blacks (37.1%), followed by non-Hispanic whites (whites; 29.5%). Previous studies have shown that the majority of TB cases in the United States are attributed to reactivation of latent TB infection (LTBI) (2). Ongoing efforts to prevent TB transmission and disease in the United States remain important to continued progress toward TB elimination. Testing and treatment of populations most at risk for TB disease and LTBI, including persons born in countries with high TB prevalence and persons in high-risk congregate settings (3), are major components of this effort.


Subject(s)
Population Surveillance , Tuberculosis/epidemiology , Emigrants and Immigrants/statistics & numerical data , Ethnicity/statistics & numerical data , Humans , Incidence , Racial Groups/statistics & numerical data , Tuberculosis/ethnology , United States/epidemiology
10.
MMWR Morb Mortal Wkly Rep ; 66(11): 289-294, 2017 Mar 24.
Article in English | MEDLINE | ID: mdl-28333908

ABSTRACT

In 2016, a total of 9,287 new tuberculosis (TB) cases were reported in the United States; this provisional* count represents the lowest number of U.S. TB cases on record and a 2.7% decrease from 2015 (1). The 2016 TB incidence of 2.9 cases per 100,000 persons represents a slight decrease compared with 2015 (-3.4%) (Figure). However, epidemiologic modeling demonstrates that if similar slow rates of decline continue, the goal of U.S. TB elimination will not be reached during this century (2). Although current programs to identify and treat active TB disease must be maintained and strengthened, increased measures to identify and treat latent TB infection (LTBI) among populations at high risk are also needed to accelerate progress toward TB elimination.


Subject(s)
Population Surveillance , Tuberculosis/epidemiology , Disease Eradication , Emigrants and Immigrants/statistics & numerical data , Ethnicity/statistics & numerical data , Humans , Incidence , Racial Groups/statistics & numerical data , Risk Factors , Tuberculosis/ethnology , Tuberculosis/prevention & control , United States/epidemiology
11.
MMWR Morb Mortal Wkly Rep ; 65(11): 273-8, 2016 Mar 25.
Article in English | MEDLINE | ID: mdl-27010173

ABSTRACT

After 2 decades of progress toward tuberculosis (TB) elimination with annual decreases of ≥0.2 cases per 100,000 persons (1), TB incidence in the United States remained approximately 3.0 cases per 100,000 persons during 2013-2015. Preliminary data reported to the National Tuberculosis Surveillance System indicate that TB incidence among foreign-born persons in the United States (15.1 cases per 100,000) has remained approximately 13 times the incidence among U.S.-born persons (1.2 cases per 100,000). Resuming progress toward TB elimination in the United States will require intensification of efforts both in the United States and globally, including increasing U.S. efforts to detect and treat latent TB infection, strengthening systems to interrupt TB transmission in the United States and globally, accelerating reductions in TB globally, particularly in the countries of origin for most U.S.


Subject(s)
Population Surveillance , Tuberculosis/epidemiology , Emigration and Immigration/statistics & numerical data , Humans , Incidence , United States/epidemiology
12.
Breast Cancer Res Treat ; 151(1): 57-73, 2015 May.
Article in English | MEDLINE | ID: mdl-25859923

ABSTRACT

Metabotropic glutamate receptor 1 (mGluR1/Grm1) is a member of the G-protein-coupled receptor superfamily, which was once thought to only participate in synaptic transmission and neuronal excitability, but has more recently been implicated in non-neuronal tissue functions. We previously described the oncogenic properties of Grm1 in cultured melanocytes in vitro and in spontaneous melanoma development with 100 % penetrance in vivo. Aberrant mGluR1 expression was detected in 60-80 % of human melanoma cell lines and biopsy samples. As most human cancers are of epithelial origin, we utilized immortalized mouse mammary epithelial cells (iMMECs) as a model system to study the transformative properties of Grm1. We introduced Grm1 into iMMECs and isolated several stable mGluR1-expressing clones. Phenotypic alterations in mammary acinar architecture were assessed using three-dimensional morphogenesis assays. We found that mGluR1-expressing iMMECs exhibited delayed lumen formation in association with decreased central acinar cell death, disrupted cell polarity, and a dramatic increase in the activation of the mitogen-activated protein kinase pathway. Orthotopic implantation of mGluR1-expressing iMMEC clones into mammary fat pads of immunodeficient nude mice resulted in mammary tumor formation in vivo. Persistent mGluR1 expression was required for the maintenance of the tumorigenic phenotypes in vitro and in vivo, as demonstrated by an inducible Grm1-silencing RNA system. Furthermore, mGluR1 was found be expressed in human breast cancer cell lines and breast tumor biopsies. Elevated levels of extracellular glutamate were observed in mGluR1-expressing breast cancer cell lines and concurrent treatment of MCF7 xenografts with glutamate release inhibitor, riluzole, and an AKT inhibitor led to suppression of tumor progression. Our results are likely relevant to human breast cancer, highlighting a putative role of mGluR1 in the pathophysiology of breast cancer and the potential of mGluR1 as a novel therapeutic target.


Subject(s)
Breast Neoplasms/genetics , Cell Proliferation/genetics , Cell Transformation, Neoplastic/genetics , Receptors, Metabotropic Glutamate/genetics , Animals , Apoptosis/genetics , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Female , Gene Expression Regulation, Neoplastic/drug effects , Heterocyclic Compounds, 3-Ring/administration & dosage , Humans , MCF-7 Cells , Mammary Glands, Animal/drug effects , Mammary Glands, Animal/pathology , Mice , Receptors, Metabotropic Glutamate/biosynthesis , Riluzole/administration & dosage , Xenograft Model Antitumor Assays
13.
MMWR Morb Mortal Wkly Rep ; 64(10): 265-9, 2015 Mar 20.
Article in English | MEDLINE | ID: mdl-25789741

ABSTRACT

In 2014, a total of 9,412 new tuberculosis (TB) cases were reported in the United States, with an incidence rate of 3.0* cases per 100,000 persons, a decrease of 2.2% from 2013. Although overall numbers of TB cases and rates continue to decline, the percentage decrease in rate is the smallest decrease in over a decade (1). This report summarizes provisional TB surveillance data reported to CDC's National Tuberculosis Surveillance System for 2014. TB cases and rates decreased among U.S.-born persons, and although the case rate also decreased among foreign-born persons, there was an increase in total number of cases among foreign-born persons. The rate among foreign-born persons in the United States in 2014 was 13.4 times higher than among U.S.-born persons. Racial/ethnic minorities continue to be disproportionately affected by TB within the United States. Asians continue to be the racial/ethnic group with the largest number of TB cases. Compared with non-Hispanic whites, the TB rate among Asians was 28.5 times higher, whereas rates among non-Hispanic blacks and Hispanics were each eight times higher. Four states (California, Texas, New York, and Florida), representing approximately one third of the U.S. population, accounted for half of all TB cases reported in 2014. Continued progress toward TB elimination in the United States will require focused TB control efforts among populations and in geographic areas with disproportionate burdens of TB.


Subject(s)
Population Surveillance , Tuberculosis/epidemiology , Black or African American/statistics & numerical data , Asian/statistics & numerical data , Hispanic or Latino/statistics & numerical data , Humans , Incidence , Tuberculosis/ethnology , United States/epidemiology , White People/statistics & numerical data
14.
Nature ; 461(7263): 495-500, 2009 Sep 24.
Article in English | MEDLINE | ID: mdl-19741607

ABSTRACT

In epithelial tissues, the lineage relationship between normal progenitor cells and cell type(s) of origin for cancer has been poorly understood. Here we show that a known regulator of prostate epithelial differentiation, the homeobox gene Nkx3-1, marks a stem cell population that functions during prostate regeneration. Genetic lineage-marking demonstrates that rare luminal cells that express Nkx3-1 in the absence of testicular androgens (castration-resistant Nkx3-1-expressing cells, CARNs) are bipotential and can self-renew in vivo, and single-cell transplantation assays show that CARNs can reconstitute prostate ducts in renal grafts. Functional assays of Nkx3-1 mutant mice in serial prostate regeneration suggest that Nkx3-1 is required for stem cell maintenance. Furthermore, targeted deletion of the Pten tumour suppressor gene in CARNs results in rapid carcinoma formation after androgen-mediated regeneration. These observations indicate that CARNs represent a new luminal stem cell population that is an efficient target for oncogenic transformation in prostate cancer.


Subject(s)
Cell Lineage , Epithelial Cells/pathology , Neoplastic Stem Cells/pathology , Prostatic Neoplasms/pathology , Androgens/deficiency , Androgens/metabolism , Animals , Castration , Cell Differentiation , Cell Division , Cell Transformation, Neoplastic , Epithelial Cells/metabolism , Epithelial Cells/transplantation , Gene Expression Regulation , Homeodomain Proteins/genetics , Homeodomain Proteins/metabolism , Kidney , Male , Mice , Mice, Inbred C57BL , Mice, Nude , Neoplastic Stem Cells/metabolism , Neoplastic Stem Cells/transplantation , PTEN Phosphohydrolase/deficiency , PTEN Phosphohydrolase/genetics , Prostatic Neoplasms/genetics , Prostatic Neoplasms/metabolism , Regeneration , Transcription Factors/genetics , Transcription Factors/metabolism
15.
Development ; 138(18): 3885-95, 2011 Sep.
Article in English | MEDLINE | ID: mdl-21862554

ABSTRACT

The signaling pathway for Nodal, a ligand of the TGFß superfamily, plays a central role in regulating the differentiation and/or maintenance of stem cell types that can be derived from the peri-implantation mouse embryo. Extra-embryonic endoderm stem (XEN) cells resemble the primitive endoderm of the blastocyst, which normally gives rise to the parietal and the visceral endoderm in vivo, but XEN cells do not contribute efficiently to the visceral endoderm in chimeric embryos. We have found that XEN cells treated with Nodal or Cripto (Tdgf1), an EGF-CFC co-receptor for Nodal, display upregulation of markers for visceral endoderm as well as anterior visceral endoderm (AVE), and can contribute to visceral endoderm and AVE in chimeric embryos. In culture, XEN cells do not express Cripto, but do express the related EGF-CFC co-receptor Cryptic (Cfc1), and require Cryptic for Nodal signaling. Notably, the response to Nodal is inhibited by the Alk4/Alk5/Alk7 inhibitor SB431542, but the response to Cripto is unaffected, suggesting that the activity of Cripto is at least partially independent of type I receptor kinase activity. Gene set enrichment analysis of genome-wide expression signatures generated from XEN cells under these treatment conditions confirmed the differing responses of Nodal- and Cripto-treated XEN cells to SB431542. Our findings define distinct pathways for Nodal and Cripto in the differentiation of visceral endoderm and AVE from XEN cells and provide new insights into the specification of these cell types in vivo.


Subject(s)
Cell Differentiation/genetics , Embryonic Stem Cells/physiology , Endoderm/cytology , Endoderm/physiology , Epidermal Growth Factor/physiology , Membrane Glycoproteins/physiology , Neoplasm Proteins/physiology , Nodal Protein/physiology , Animals , Cell Differentiation/drug effects , Cell Line , Embryo, Mammalian , Embryonic Stem Cells/drug effects , Embryonic Stem Cells/metabolism , Endoderm/drug effects , Endoderm/metabolism , Epidermal Growth Factor/genetics , Epidermal Growth Factor/metabolism , Epidermal Growth Factor/pharmacology , Extraembryonic Membranes/cytology , Extraembryonic Membranes/physiology , Female , Gene Expression Profiling , Membrane Glycoproteins/genetics , Membrane Glycoproteins/metabolism , Membrane Glycoproteins/pharmacology , Mice , Mice, Inbred ICR , Mice, Transgenic , Microarray Analysis , Neoplasm Proteins/genetics , Neoplasm Proteins/metabolism , Neoplasm Proteins/pharmacology , Nodal Protein/genetics , Nodal Protein/metabolism , Nodal Protein/pharmacology , Pregnancy , Signal Transduction/drug effects , Signal Transduction/genetics
16.
MMWR Morb Mortal Wkly Rep ; 63(11): 229-33, 2014 Mar 21.
Article in English | MEDLINE | ID: mdl-24647398

ABSTRACT

In 2013, a total of 9,588 new tuberculosis (TB) cases were reported in the United States, with an incidence rate of 3.0 cases per 100,000 population, a decrease of 4.2% from 2012. This report summarizes provisional TB surveillance data reported to CDC in 2013. Although case counts and incidence rates continue to decline, certain populations are disproportionately affected. The TB incidence rate among foreign-born persons in 2013 was approximately 13 times greater than the incidence rate among U.S.-born persons, and the proportion of TB cases occurring in foreign-born persons continues to increase, reaching 64.6% in 2013. Racial/ethnic disparities in TB incidence persist, with TB rates among non-Hispanic Asians almost 26 times greater than among non-Hispanic whites. Four states (California, Texas, New York, and Florida), home to approximately one third of the U.S. population, accounted for approximately half the TB cases reported in 2013. The proportion of TB cases occurring in these four states increased from 49.9% in 2012 to 51.3% in 2013. Continued progress toward TB elimination in the United States will require focused TB control efforts among populations and in geographic areas with disproportionate burdens of TB.


Subject(s)
Health Status Disparities , Population Surveillance , Tuberculosis/epidemiology , Black or African American/statistics & numerical data , Asian/statistics & numerical data , Hispanic or Latino/statistics & numerical data , Humans , Incidence , Tuberculosis/ethnology , United States/epidemiology , White People/statistics & numerical data
17.
Dev Dyn ; 242(10): 1160-71, 2013 Oct.
Article in English | MEDLINE | ID: mdl-23813564

ABSTRACT

BACKGROUND: The formation of the prostate gland requires reciprocal interactions between the epithelial and mesenchymal components of the embryonic urogenital sinus. However, the identity of the signaling factors that mediate these interactions is largely unknown. RESULTS: Our studies show that expression of the prostate-specific transcription factor Nkx3.1 is regulated by the canonical Wnt signaling pathway. Using mice carrying a targeted lacZ knock-in allele of Nkx3.1, we find that Nkx3.1 is expressed in all epithelial cells of ductal buds during prostate organogenesis. Addition of Wnt inhibitors to urogenital sinus explant culture greatly reduces prostate budding and inhibits Nkx3.1 expression as well as differentiation of luminal epithelial cells. Analyses of a TCF/Lef:H2B-GFP transgene reporter show that canonical Wnt signaling activity is found in urogenital mesenchyme but not urogenital sinus epithelium before prostate formation, and is later observed in the mesenchyme and epithelium of prostate ductal tips. Furthermore, TCF/Lef:H2B-GFP reporter activity is reduced in epithelial cells of Nkx3.1 null neonatal prostates, suggesting that Nkx3.1 functions to maintain canonical Wnt signaling activity in developing prostate bud tips. CONCLUSIONS: We propose that activated canonical Wnt signals and Nkx3.1 function in a positive feedback loop to regulate prostate bud growth and luminal epithelial differentiation.


Subject(s)
Epithelial Cells/metabolism , Gene Expression Regulation, Developmental/physiology , Homeodomain Proteins/biosynthesis , Organogenesis/physiology , Prostate/embryology , Transcription Factors/biosynthesis , Wnt Signaling Pathway/physiology , Animals , Epithelial Cells/cytology , Homeodomain Proteins/genetics , Male , Mice , Mice, Transgenic , Prostate/cytology , Transcription Factors/genetics , Wnt Proteins/genetics , Wnt Proteins/metabolism
18.
Mo Med ; 111(3): 202-6, 2014.
Article in English | MEDLINE | ID: mdl-25011341

ABSTRACT

Tourette Syndrome (TS) is recognized as a more common neurodevelopmental disorder than once thought. In this article we present an update on TS including the DSM-5 revised criteria, new findings in the genetics of TS, treatment advances such as new medications for tics and the use of new tools including Cognitive Behavioral Intervention for Tics (CBIT). We also explore supportive services for the ongoing care of patients using nursing education and family therapy.


Subject(s)
Tourette Syndrome/epidemiology , Tourette Syndrome/therapy , Cognitive Behavioral Therapy , Comorbidity , Environmental Exposure , Family , Genetic Predisposition to Disease , Humans , Tourette Syndrome/genetics
19.
BMC Public Health ; 11: 846, 2011 Nov 07.
Article in English | MEDLINE | ID: mdl-22059421

ABSTRACT

BACKGROUND: Since 1953, through the cooperation of state and local health departments, the U.S. Centers for Disease Control and Prevention (CDC) has collected information on incident cases of tuberculosis (TB) disease in the United States. In 2009, TB case rates declined -11.4%, compared to an average annual -3.8% decline since 2000. The unexpectedly large decline raised concerns that TB cases may have gone unreported. To address the unexpected decline, we examined trends from multiple sources on TB treatment initiation, medication sales, and laboratory and genotyping data on culture-positive TB. METHODS: We analyzed 142,174 incident TB cases reported to the U. S. National Tuberculosis Surveillance System (NTSS) during January 1, 2000-December 31, 2009; TB control program data from 59 public health reporting areas; self-reported data from 50 CDC-funded public health laboratories; monthly electronic prescription claims for new TB therapy prescriptions; and complete genotyping results available for NTSS cases. Accounting for prior trends using regression and time-series analyses, we calculated the deviation between observed and expected TB cases in 2009 according to patient and clinical characteristics, and assessed at what point in time the deviation occurred. RESULTS: The overall deviation in TB cases in 2009 was -7.9%, with -994 fewer cases reported than expected (P < .001). We ruled out evidence of surveillance underreporting since declines were seen in states that used new software for case reporting in 2009 as well as states that did not, and we found no cases unreported to CDC in our examination of over 5400 individual line-listed reports in 11 areas. TB cases decreased substantially among both foreign-born and U.S.-born persons. The unexpected decline began in late 2008 or early 2009, and may have begun to reverse in late 2009. The decline was greater in terms of case counts among foreign-born than U.S.-born persons; among the foreign-born, the declines were greatest in terms of percentage deviation from expected among persons who had been in the United States less than 2 years. Among U.S.-born persons, the declines in percentage deviation from expected were greatest among homeless persons and substance users. Independent information systems (NTSS, TB prescription claims, and public health laboratories) reported similar patterns of declines. Genotyping data did not suggest sudden decreases in recent transmission. CONCLUSIONS: Our assessments show that the decline in reported TB was not an artifact of changes in surveillance methods; rather, similar declines were found through multiple data sources. While the steady decline of TB cases before 2009 suggests ongoing improvement in TB control, we were not able to identify any substantial change in TB control activities or TB transmission that would account for the abrupt decline in 2009. It is possible that other multiple causes coincident with economic recession in the United States, including decreased immigration and delayed access to medical care, could be related to TB declines. Our findings underscore important needs in addressing health disparities as we move towards TB elimination in the United States.


Subject(s)
Economic Recession/statistics & numerical data , Population Surveillance , Tuberculosis/epidemiology , Emigrants and Immigrants/statistics & numerical data , Humans , Incidence , United States/epidemiology
20.
Article in English | MEDLINE | ID: mdl-33381280

ABSTRACT

BACKGROUND: With the rapid development of new advanced molecular detection methods, identification of new genetic mutations conferring pathogen resistance to an ever-growing variety of antimicrobial substances will generate massive genomic datasets for public health and clinical laboratories. Keeping up with specialized standard coding for these immense datasets will be extremely challenging. This challenge prompted our effort to create a common molecular resistance Logical Observation Identifiers Names and Codes (LOINC) panel that can be used to report any identified antimicrobial resistance pattern. OBJECTIVE: To develop and utilize a common molecular resistance LOINC panel for molecular drug susceptibility testing (DST) data exchange in the U.S. National Tuberculosis Surveillance System using California Department of Public Health (CDPH) and New York State Department of Health as pilot sites. METHODS: We developed an interface and mapped incoming molecular DST data to the common molecular resistance LOINC panel using Health Level Seven (HL7) v2.5.1 Electronic Laboratory Reporting (ELR) message specifications through the Orion Health™ Rhapsody Integration Engine v6.3.1. RESULTS: Both pilot sites were able to process and upload/import the standardized HL7 v2.5.1 ELR messages into their respective systems; albeit CDPH identified areas for system improvements and has focused efforts to streamline the message importation process. Specifically, CDPH is enhancing their system to better capture parent-child elements and ensure that the data collected can be accessed seamlessly by the U.S. Centers for Disease Control and Prevention. DISCUSSION: The common molecular resistance LOINC panel is designed to be generalizable across other resistance genes and ideally also applicable to other disease domains. CONCLUSION: The study demonstrates that it is possible to exchange molecular DST data across the continuum of disparate healthcare information systems in integrated public health environments using the common molecular resistance LOINC panel.

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