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1.
J Pediatr ; 271: 114056, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38615943

ABSTRACT

OBJECTIVE: To evaluate the prevalence, trends, and factors associated with psychotropic medication use and polypharmacy among children and adolescents initiating intensive behavioral therapy for severe challenging behavior over a 10-year period. STUDY DESIGN: In this retrospective observational study, we examined data from caregiver interviews and patient medical records on the number and types of psychotropic medications prescribed to patients initiating intensive behavioral therapy between January 1, 2013, and December 31, 2022. Trends in medication use and polypharmacy across the 10-year period were analyzed using regression analysis, while differences in demographics and clinical factors for patients with use and polypharmacy were analyzed using nonparametric statistical analysis with odds ratios presented for significant factors. RESULTS: Data from all 302 pediatric patients initiating intensive behavioral therapy across the 10-year period were analyzed. Among all patients and all years, 83.8% were taking at least 1 psychotropic medication and 68.2% experienced polypharmacy. There were no changes in the prevalence of use, mean number of medications taken, or polypharmacy across the 10-year period. Patients diagnosed with attention-deficit/hyperactivity disorder or anxiety disorder, as well as those exhibiting self-injurious behavior had higher use of psychotropic medication and polypharmacy and were taking more medications overall. CONCLUSIONS: Psychotropic medication use and polypharmacy were extremely high for children and adolescents with severe challenging behavior, but use and polypharmacy did not change over the 10-year period of data collection. Further research is needed to establish the generality of these findings to other regions of the US.


Subject(s)
Behavior Therapy , Polypharmacy , Psychotropic Drugs , Humans , Female , Male , Child , Psychotropic Drugs/therapeutic use , Retrospective Studies , Adolescent , Behavior Therapy/methods , Problem Behavior , Child, Preschool , Attention Deficit Disorder with Hyperactivity/drug therapy
2.
Med Care ; 62(1): 60-66, 2024 Jan 01.
Article in English | MEDLINE | ID: mdl-37962423

ABSTRACT

BACKGROUND: International Classification of Diseases, 10th revision Z codes capture social needs related to health care encounters and may identify elevated risk of acute care use. OBJECTIVES: To examine associations between Z code assignment and subsequent acute care use and explore associations between social need category and acute care use. RESEARCH DESIGN: Retrospective cohort study. SUBJECTS: Adults continuously enrolled in a commercial or Medicare Advantage plan for ≥15 months (12-month baseline, 3-48 month follow-up). OUTCOMES: All-cause emergency department (ED) visits and inpatient admissions during study follow-up. RESULTS: There were 352,280 patients with any assigned Z codes and 704,560 sampled controls with no Z codes. Among patients with commercial plans, Z code assignment was associated with a 26% higher rate of ED visits [adjusted incidence rate ratio (aIRR) 1.26, 95% CI: 1.25-1.27] and 42% higher rate of inpatient admissions (aIRR 1.42, 95% CI: 1.39-1.44) during follow-up. Among patients with Medicare Advantage plans, Z code assignment was associated with 42% (aIRR 1.42, 95% CI: 1.40-1.43) and 28% (aIRR 1.28, 95% CI: 1.26-1.30) higher rates of ED visits and inpatient admissions, respectively. Within the Z code group, relative to community/social codes, socioeconomic Z codes were associated with higher rates of inpatient admissions (commercial: aIRR 1.10, 95% CI: 1.06-1.14; Medicare Advantage: aIRR 1.24, 95% CI 1.20-1.27), and environmental Z codes were associated with lower rates of both primary outcomes. CONCLUSIONS: Z code assignment was independently associated with higher subsequent emergency and inpatient utilization. Findings suggest Z codes' potential utility for risk prediction and efforts targeting avoidable utilization.


Subject(s)
Inpatients , Medicare Part C , Adult , Humans , United States , Aged , Retrospective Studies , International Classification of Diseases , Hospitalization , Emergency Service, Hospital
3.
J Immunol ; 209(5): 991-1000, 2022 09 01.
Article in English | MEDLINE | ID: mdl-36130126

ABSTRACT

Akt-1 and Akt-2 are the major isoforms of the serine/threonine Akt family that play a key role in controlling immune responses. However, the involvement of Akt-1 and Akt-2 isoforms in antifungal innate immunity is completely unknown. In this study, we show that Akt2 -/-, but not Akt1 -/-, mice are protected from lethal Candida albicans infection. Loss of Akt-2 facilitates the recruitment of neutrophils and macrophages to the spleen and increases reactive oxygen species expression in these cells. Treating C57BL/6 mice with a specific inhibitor for Akt-2, but not Akt-1, provides protection from lethal C. albicans infection. Our data demonstrate that Akt-2 inhibits antifungal innate immunity by hampering neutrophil and macrophage recruitment to spleens and suppressing oxidative burst, myeloperoxidase activity, and NETosis. We thus describe a novel role for Akt-2 in the regulation of antifungal innate immunity and unveil Akt-2 as a potential target for the treatment of fungal sepsis.


Subject(s)
Candida albicans , Candidiasis , Proto-Oncogene Proteins c-akt/metabolism , Animals , Antifungal Agents , Mice , Mice, Inbred C57BL , Neutrophils , Peroxidase/metabolism , Reactive Oxygen Species/metabolism , Serine/metabolism , Threonine/metabolism
4.
J Chem Ecol ; 2024 Aug 12.
Article in English | MEDLINE | ID: mdl-39133432

ABSTRACT

Odontothrips loti (Haliday) (Thysanoptera: Thripidae) is one of the most serious pests on alfalfa, causing direct damage by feeding and indirect damage by transmitting plant viruses. This damage causes significant loss in alfalfa production. Semiochemicals offer opportunities to develop new approaches to thrips management. In this study, behavioral responses of female and male adults of O. loti to headspace volatiles from live female and male conspecifics were tested in a Y-tube olfactometer. The results showed that both male and female adults of O. loti were attracted to the odors released by conspecific males but not those released by females. Headspace volatiles released by female and male adults were collected using headspace solid-phase microextraction (HS-SPME). The active compound in the volatiles was identified by gas chromatography-mass spectrometry (GC-MS). The analysis showed that there was one major compound, (R)-lavandulyl (R)-2-methylbutanoate. The attractive activity of the synthetic aggregation pheromone compound was tested under laboratory and field conditions. In an olfactometer, both male and female adults showed significant preference for synthetic (R)-lavandulyl (R)-2-methylbutanoate at certain doses. Lures with synthetic (R)-lavandulyl (R)-2-methylbutanoate significantly increased the trap catches of sticky white traps at doses of 40-80 µg in the field. This study confirmed the production of aggregation pheromone by O. loti male adults and identified its active compound as (R)-lavandulyl (R)-2-methylbutanoate, providing a basis for population monitoring and mass trapping of this pest.

5.
BMC Public Health ; 24(1): 2699, 2024 Oct 03.
Article in English | MEDLINE | ID: mdl-39363167

ABSTRACT

BACKGROUND: Tourette syndrome (TS) is a neurodevelopmental disorder. The prevalence of TS in 2016-2017 has been reported; however, little is known about the current prevalence and trend in children and adolescents with TS. This study aimed to estimate the prevalence and trend of Tourette syndrome (TS) among US children and adolescents aged 0-17 years from 2016 to 2022. METHODS: We analyzed data from a nationally representative sample of 278,472 children and adolescents aged 0-17 years who participated in the 2016-2022 National Survey of Children's Health (NSCH), a nationwide, population-based, cross-sectional survey of US children and adolescents. TS was defined as the affirmative response in the questionnaire completed by a parent or guardian. RESULTS: Among the 278,472 children and adolescents enrolled, 754 had been diagnosed with TS, with an overall prevalence of 0.23% in all children and adolescents aged 0-17 years. The weighted prevalence by age group was lower than 0.01% in children aged 0-2 years, 0.05% in children aged 3-5 years, 0.28% in children aged 6-11 years, and 0.38% in adolescents aged 12-17 years. There were significant sex and racial/ethnic differences in the overall prevalence of diagnosed TS (i.e., 0.35% in boys and 0.11% in girls, 0.22% in Hispanics, 0.28% in non-Hispanic whites and 0.16% in non-Hispanic blacks). There was no significant change in the estimated prevalence of TS from 2016 to 2022. CONCLUSION: Based on nationally representative data, this study found that the national prevalence of TS among the US children and adolescents differed by sex and race/ethnicity but remained stable from 2016 to 2022.


Subject(s)
Tourette Syndrome , Humans , Tourette Syndrome/epidemiology , Adolescent , United States/epidemiology , Child , Male , Female , Prevalence , Child, Preschool , Cross-Sectional Studies , Infant , Infant, Newborn , Health Surveys
6.
J Gen Intern Med ; 38(16): 3541-3548, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37731136

ABSTRACT

BACKGROUND: In 2021, the U.S. Preventive Services Task Force (USPSTF) recommended screening for prediabetes and diabetes among adults aged 35-70 years with overweight or obesity. Studying dysglycemia screening in federally qualified health centers (FQHCs) that serve vulnerable patient populations is needed to understand health equity implications of this recommendation. OBJECTIVE: To investigate screening practices among FQHC patients who would be eligible according to the 2021 USPSTF recommendation. DESIGN: Retrospective cohort study analyzing electronic health records from a national network of 282 FQHC sites. PARTICIPANTS: We included 183,329 patients without prior evidence of prediabetes or diabetes, who had ≥ 1 office visit from 2018-2020. MAIN MEASURES: Screening eligibility was based on age and measured body mass index (BMI). The primary outcome, screening completion, was ascertained using hemoglobin A1c or fasting plasma glucose results from 2018-2020. KEY RESULTS: Among 89,543 patients who would be eligible according to the 2021 USPSTF recommendation, 53,263 (59.5%) were screened. Those who completed screening had higher BMI values than patients who did not (33.0 ± 6.7 kg/m2 vs. 31.9 ± 6.2 kg/m2, p < 0.001). Adults aged 50-64 years had greater odds of screening completion relative to younger patients (OR 1.13, 95% CI: 1.10-1.17). Patients from racial and ethnic minority groups, as well as those without health insurance, were more likely to complete screening than White patients and insured patients, respectively. Clinical risk factors for diabetes were also associated with dysglycemia screening. Among patients who completed screening, 23,588 (44.3%) had values consistent with prediabetes or diabetes. CONCLUSIONS: Over half of FQHC patients who would be eligible according to the 2021 USPSTF recommendation were screened. Screening completion was higher among middle-aged patients, those with greater BMI values, as well as vulnerable groups with a high risk of developing diabetes. Future research should examine adoption of the 2021 USPSTF screening recommendation and its impact on health equity.


Subject(s)
Diabetes Mellitus , Prediabetic State , Adult , Middle Aged , Humans , Prediabetic State/diagnosis , Prediabetic State/epidemiology , Ethnicity , Retrospective Studies , Minority Groups , Diabetes Mellitus/diagnosis , Diabetes Mellitus/epidemiology , Mass Screening/methods
7.
Ann Fam Med ; 21(Suppl 2): S68-S74, 2023 02.
Article in English | MEDLINE | ID: mdl-36849484

ABSTRACT

PURPOSE: Integrating social care into clinical care requires substantial resources. Use of existing data through a geographic information system (GIS) has the potential to support efficient and effective integration of social care into clinical settings. We conducted a scoping literature review characterizing its use in primary care settings to identify and address social risk factors. METHODS: In December 2018, we searched 2 databases and extracted structured data for eligible articles that (1) described the use of GIS in clinical settings to identify and/or intervene on social risks, (2) were published between December 2013 and December 2018, and (3) were based in the United States. Additional studies were identified by examining references. RESULTS: Of the 5,574 articles included for review, 18 met study eligibility criteria: 14 (78%) were descriptive studies, 3 (17%) tested an intervention, and 1 (6%) was a theoretical report. All studies used GIS to identify social risks (increase awareness); 3 studies (17%) described interventions to address social risks, primarily by identifying relevant community resources and aligning clinical services to patients' needs. CONCLUSIONS: Most studies describe associations between GIS and population health outcomes; however, there is a paucity of literature regarding GIS use to identify and address social risk factors in clinical settings. GIS technology may assist health systems seeking to address population health outcomes through alignment and advocacy; its current application in clinical care delivery is infrequent and largely limited to referring patients to local community resources.


Subject(s)
Social Support , Technology , Humans , Databases, Factual
8.
J Am Pharm Assoc (2003) ; 63(3): 769-777, 2023.
Article in English | MEDLINE | ID: mdl-36682933

ABSTRACT

INTRODUCTION: Type 2 diabetes mellitus (T2DM) and comorbid conditions require patients to take complex medication regimens. Greater regimen complexity has been associated with poorer T2DM management; however, the relationship between overall regimen complexity and glycemic control is unclear. OBJECTIVES: Our objectives were: (1) to examine associations between regimen complexity (with the Medication Regimen Complexity Index [MRCI]) and glycemic control (A1C), and (2) to compare overall MRCI with other measures of regimen complexity (overall and diabetes-specific medication count) and diabetes-specific MRCI. METHODS: This was a secondary data analysis of cross-sectional data from a parent trial. Participants were patients with T2DM taking at least 3 chronic medications followed in safety net clinics in the Chicago area. The MRCI measures complexity based on dosing frequency, route of administration, and special instructions for prescribed medications. MRCI scores were created for overall regimens and diabetes-specific medications. Sociodemographics and outpatient visit utilization were included in models as covariates. Linear regression was used to examine the associations between variables of interest and hemoglobin A1C. RESULTS: Participants (N = 432) had a mean age of 56.9 years, most were female (66.0%), and Hispanic or Latino (73.3%). Regimen complexity was high based on overall medications (mean = 6.6 medications, SD: 3.09) and MRCI (mean = 21.4, SD: 11.3). Higher diabetes-specific MRCI was associated with higher A1C in bivariate and multivariable models. In multivariable models, overall MRCI greater than 14, fewer outpatient health care visits, male gender, and absence of health insurance were independently associated with higher A1C. The variance in A1C explained by MRCI was higher compared to medication count for overall and diabetes-specific regimen complexity. CONCLUSIONS: More complex regimens are associated with worse A1C and measuring complexity with MRCI may have advantages. Deprescribing, increasing insurance coverage, and promoting engagement in health care may improve A1C among underserved populations with complex regimens.


Subject(s)
Diabetes Mellitus, Type 2 , Female , Humans , Male , Middle Aged , Cross-Sectional Studies , Diabetes Mellitus, Type 2/drug therapy , Glycated Hemoglobin , Glycemic Control , Pharmaceutical Preparations , Retrospective Studies
9.
JAMA ; 330(4): 359-367, 2023 07 25.
Article in English | MEDLINE | ID: mdl-37490084

ABSTRACT

Importance: Poor prepregnancy cardiovascular health (CVH) and adverse pregnancy outcomes (APOs) are key risk factors for subsequent cardiovascular disease (CVD) in birthing adults. The postpartum visit offers an opportunity to promote CVH among at-risk individuals. Objective: To determine prevalence, predictors, and trends in self-reported CVH counseling during the postpartum visit. Design, Setting, and Participants: Serial, cross-sectional analysis of data from 2016-2020 from the Pregnancy Risk Assessment Monitoring System (PRAMS), a nationally representative, population-based survey. The primary analysis included individuals who attended a postpartum visit 4 to 6 weeks after delivery with available data on receipt of CVH counseling, self-reported prepregnancy CVD risk factors (obesity, diabetes, and hypertension), and APOs (gestational diabetes, hypertensive disorders of pregnancy, and preterm birth) (N = 167 705 [weighted N = 8 714 459]). Exposures: Total number of CVD risk factors (0, 1, or ≥2 prepregnancy risk factors or APOs). Main Outcomes and Measures: Annual, age-adjusted prevalence of self-reported postpartum CVH counseling per 100 individuals, defined as receipt of counseling for healthy eating, exercise, and losing weight gained during pregnancy, was calculated overall and by number of CVD risk factors. Average annual percent change (APC) assessed trends in CVH counseling from 2016 through 2020. Data were pooled to calculate rate ratios (RRs) for counseling that compared individuals with and without CVD risk factors after adjustment for age, education, postpartum insurance, and delivery year. Results: From 2016 through 2020, prevalence of self-reported postpartum CVH counseling declined from 56.2 to 52.8 per 100 individuals among those with no CVD risk factors (APC, -1.4% [95% CI, -1.8% to -1.0%/y]), from 58.5 to 57.3 per 100 individuals among those with 1 risk factor (APC, -0.7% [95% CI, -1.3% to -0.1%/y]), and from 61.9 to 59.8 per 100 individuals among those with 2 or more risk factors (APC, -0.8% [95% CI, -1.3% to -0.3%/y]). Reporting receipt of counseling was modestly higher among individuals with 1 risk factor (RR, 1.05 [95% CI, 1.04 to 1.07]) and with 2 or more risk factors (RR, 1.11 [95% CI, 1.09 to 1.13]) compared with those who had no risk factors. Conclusions and Relevance: Approximately 60% of individuals with CVD risk factors or APOs reported receiving CVH counseling at their postpartum visit. Prevalence of reporting CVH counseling decreased modestly over 5 years.


Subject(s)
Counseling , Heart Disease Risk Factors , Pregnancy Complications, Cardiovascular , Adult , Female , Humans , Infant, Newborn , Pregnancy , Cardiovascular System , Cross-Sectional Studies , Hypertension/epidemiology , Parturition , Postpartum Period , Premature Birth/epidemiology , Counseling/trends , Pregnancy Complications, Cardiovascular/epidemiology , Pregnancy Complications, Cardiovascular/therapy , United States/epidemiology , Risk , Prevalence , Pregnancy Complications/epidemiology , Pregnancy Outcome/epidemiology
10.
Int J Mol Sci ; 25(1)2023 Dec 28.
Article in English | MEDLINE | ID: mdl-38203602

ABSTRACT

Up to 50% of patients with severe congenital heart disease (CHD) develop life-altering neurodevelopmental disability (NDD). It has been presumed that NDD arises in CHD cases because of hypoxia before, during, or after cardiac surgery. Recent studies detected an enrichment in de novo mutations in CHD and NDD, as well as significant overlap between CHD and NDD candidate genes. However, there is limited evidence demonstrating that genes causing CHD can produce NDD independent of hypoxia. A patient with hypoplastic left heart syndrome and gross motor delay presented with a de novo mutation in SMC5. Modeling mutation of smc5 in Xenopus tropicalis embryos resulted in reduced heart size, decreased brain length, and disrupted pax6 patterning. To evaluate the cardiac development, we induced the conditional knockout (cKO) of Smc5 in mouse cardiomyocytes, which led to the depletion of mature cardiomyocytes and abnormal contractility. To test a role for Smc5 specifically in the brain, we induced cKO in the mouse central nervous system, which resulted in decreased brain volume, and diminished connectivity between areas related to motor function but did not affect vascular or brain ventricular volume. We propose that genetic factors, rather than hypoxia alone, can contribute when NDD and CHD cases occur concurrently.


Subject(s)
Heart Defects, Congenital , Humans , Animals , Mice , Heart Defects, Congenital/genetics , Brain , Heart Ventricles , Hypoxia , Myocytes, Cardiac , Xenopus , Chromosomal Proteins, Non-Histone , Cell Cycle Proteins/genetics , Xenopus Proteins
11.
Histopathology ; 81(2): 215-227, 2022 Aug.
Article in English | MEDLINE | ID: mdl-35543076

ABSTRACT

AIMS: Recurrent alterations involving receptor tyrosine or cytoplasmic kinase genes have been described in soft-tissue neoplasms such as infantile fibrosarcoma (IFS) and inflammatory myofibroblastic tumour (IMT). Recent trials and regulatory approvals for targeted inhibitors against the kinase domains of these oncoproteins have allowed for increased use of targeted therapies. We aimed to characterize the histologic features of paediatric mesenchymal neoplasms with kinase alterations treated with targeted inhibitors. METHODS AND RESULTS: Eight patients with tyrosine kinase-altered mesenchymal neoplasms with pre- and posttreatment samples were identified. Tumours occurred in five females and three males with a median age at presentation of 6.5 years. Tumour sites were bone/somatic soft-tissue (n = 5) and viscera (n = 3). Pretreatment diagnoses were: IMT (n = 3), epithelioid inflammatory myofibroblastic sarcoma (n = 1), and descriptive diagnoses (n = 4) such as "kinase-driven spindle cell tumor." Fusions identified were ETV6::NTRK3 (n = 2), TPM3::NTRK1, SEPT7::BRAF, TFG::ROS1, KLC1::ALK, RANBP2::ALK, and MAP4::RAF1. Patients were treated with larotrectinib (n = 3), ALK or ALK/ROS1 inhibitors (n = 3), and MEK inhibitors (n = 2). Posttreatment tumours exhibited a striking decrease in cellularity (7/8) and the presence of collagenous stroma (7/8) with extensive glassy hyalinization (5/8). In two cases, abundant coarse or psammomatous calcifications were seen and in one case prominent perivascular hyalinization was noted. Residual viable tumour was seen in 3/8 cases (<5% in one case, and >75% in 2/8 cases). CONCLUSION: Mesenchymal neoplasms with tyrosine kinase alterations treated with targeted inhibitors show a pathologic response, which includes decreased cellularity and stromal hyalinization. The presence of these features may be helpful in assessing tumour response after targeted therapy.


Subject(s)
Granuloma, Plasma Cell , Sarcoma , Anaplastic Lymphoma Kinase/genetics , Child , Female , Humans , Male , Protein Kinase Inhibitors/therapeutic use , Protein-Tyrosine Kinases/genetics , Proto-Oncogene Proteins/genetics , Receptor Protein-Tyrosine Kinases/genetics , Sarcoma/drug therapy , Sarcoma/genetics , Sarcoma/pathology
12.
BMC Geriatr ; 22(1): 97, 2022 02 03.
Article in English | MEDLINE | ID: mdl-35114955

ABSTRACT

BACKGROUND: Antidiabetic medications (ADM), especially sulfonylureas (SFU) and basal insulin (BI), are associated with increased risk of hypoglycemia, which is especially concerning among older adults in poor health. The objective of this study was to investigate prescribing patterns of ADM in older adults according to their health status. METHODS: This case control study analyzed administrative claims between 2013 and 2017 from a large national payer. The study population was derived from a nationwide database of 84,720 U.S. adults aged ≥65, who were enrolled in Medicare Advantage health insurance plans. Participants had type 2 diabetes on metformin monotherapy, and started a second-line ADM during the study period. The exposure was a binary variable for health status, with poor health defined by end-stage medical conditions, dementia, or residence in a long-term nursing facility. The outcome was a variable identifying which second-line ADM class was started, categorized as SFU, BI, or other (i.e. all other ADM classes combined). RESULTS: Over half of participants (54%) received SFU as initial second-line ADM, 14% received BI, and 32% received another ADM. In multivariable models, the odds of filling SFU or BI was higher for participants in poor health than those in good or intermediate health [OR 1.13 (95% CI 1.05-1.21) and OR 2.34 (95% CI 2.14-2.55), respectively]. SFU and BI were also more commonly filled by older adults with poor glycemic control. CONCLUSIONS: Despite clinical consensus to use caution prescribing SFU and BI among older adults in poor health, these medications remain frequently used in this particularly vulnerable population.


Subject(s)
Diabetes Mellitus, Type 2 , Medicare Part C , Metformin , Aged , Case-Control Studies , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/epidemiology , Humans , Hypoglycemic Agents/adverse effects , Metformin/adverse effects , United States
13.
J Biol Chem ; 295(48): 16239-16250, 2020 11 27.
Article in English | MEDLINE | ID: mdl-32913128

ABSTRACT

The calcium-calmodulin-dependent protein kinase kinase-2 (CaMKK2) is a key regulator of cellular and whole-body energy metabolism. It is known to be activated by increases in intracellular Ca2+, but the mechanisms by which it is inactivated are less clear. CaMKK2 inhibition protects against prostate cancer, hepatocellular carcinoma, and metabolic derangements induced by a high-fat diet; therefore, elucidating the intracellular mechanisms that inactivate CaMKK2 has important therapeutic implications. Here we show that stimulation of cAMP-dependent protein kinase A (PKA) signaling in cells inactivates CaMKK2 by phosphorylation of three conserved serine residues. PKA-dependent phosphorylation of Ser495 directly impairs calcium-calmodulin activation, whereas phosphorylation of Ser100 and Ser511 mediate recruitment of 14-3-3 adaptor proteins that hold CaMKK2 in the inactivated state by preventing dephosphorylation of phospho-Ser495 We also report the crystal structure of 14-3-3ζ bound to a synthetic diphosphorylated peptide that reveals how the canonical (Ser511) and noncanonical (Ser100) 14-3-3 consensus sites on CaMKK2 cooperate to bind 14-3-3 proteins. Our findings provide detailed molecular insights into how cAMP-PKA signaling inactivates CaMKK2 and reveals a pathway to inhibit CaMKK2 with potential for treating human diseases.


Subject(s)
14-3-3 Proteins/metabolism , Calcium-Calmodulin-Dependent Protein Kinase Kinase/metabolism , Cyclic AMP-Dependent Protein Kinases/metabolism , Signal Transduction , 14-3-3 Proteins/genetics , Animals , COS Cells , Calcium-Calmodulin-Dependent Protein Kinase Kinase/genetics , Cell Line, Tumor , Chlorocebus aethiops , Cyclic AMP-Dependent Protein Kinases/genetics , Enzyme Activation , Humans
14.
Cardiovasc Diabetol ; 20(1): 66, 2021 03 22.
Article in English | MEDLINE | ID: mdl-33752676

ABSTRACT

BACKGROUND: Given the rising prevalence of dysglycemia and disparities in heart failure (HF) burden, we determined race- and sex-specific lifetime risk of HF across the spectrum of fasting plasma glucose (FPG). METHODS: Individual-level data from adults without baseline HF was pooled from 6 population-based cohorts. Modified Kaplan-Meier analysis, Cox models adjusted for the competing risk of death, and Irwin's restricted mean were used to estimate the lifetime risk, adjusted hazard ratio (aHR), and years lived free from HF in middle-aged (40-59 years) and older (60-79 years) adults with FPG < 100 mg/dL, prediabetes (FPG 100-125 mg/dL) and diabetes (FPG ≥ 126 mg/dL or on antihyperglycemic agents) across race-sex groups. RESULTS: In 40,117 participants with 638,910 person-years of follow-up, 4846 cases of incident HF occurred. The lifetime risk of HF was significantly higher among middle-aged White adults and Black women with prediabetes (range: 6.1% [95% CI 4.8%, 7.4%] to 10.8% [95% CI 8.3%, 13.4%]) compared with normoglycemic adults (range: 3.5% [95% CI 3.0%, 4.1%] to 6.5% [95% CI 4.9%, 8.1%]). Middle-aged Black women with diabetes had the highest lifetime risk (32.4% [95% CI 26.0%, 38.7%]) and aHR (4.0 [95% CI 3.0, 5.4]) for HF across race-sex groups. Middle-aged adults with prediabetes and diabetes lived on average 0.9-1.6 and 4.1-6.0 fewer years free from HF, respectively. Findings were similar in older adults except older Black women with prediabetes did not have a higher lifetime risk of HF. CONCLUSIONS: Prediabetes was associated with higher lifetime risk of HF in middle-aged White adults and Black women, with the association attenuating in older Black women. Black women with diabetes had the highest lifetime risk of HF compared with other race-sex groups.


Subject(s)
Black or African American , Blood Glucose/metabolism , Diabetes Mellitus/blood , Fasting/blood , Heart Failure/ethnology , Prediabetic State/blood , White People , Adult , Aged , Biomarkers/blood , Blood Glucose/drug effects , Diabetes Mellitus/drug therapy , Diabetes Mellitus/ethnology , Diabetes Mellitus/mortality , Female , Heart Failure/mortality , Humans , Hypoglycemic Agents/therapeutic use , Incidence , Male , Middle Aged , Prediabetic State/drug therapy , Prediabetic State/ethnology , Prediabetic State/mortality , Race Factors , Risk Assessment , Risk Factors , Sex Factors , Time Factors
15.
JAMA ; 326(7): 660-669, 2021 08 17.
Article in English | MEDLINE | ID: mdl-34402831

ABSTRACT

Importance: Gestational diabetes is associated with adverse maternal and offspring outcomes. Objective: To determine whether rates of gestational diabetes among individuals at first live birth changed from 2011 to 2019 and how these rates differ by race and ethnicity in the US. Design, Setting, and Participants: Serial cross-sectional analysis using National Center for Health Statistics data for 12 610 235 individuals aged 15 to 44 years with singleton first live births from 2011 to 2019 in the US. Exposures: Gestational diabetes data stratified by the following race and ethnicity groups: Hispanic/Latina (including Central and South American, Cuban, Mexican, and Puerto Rican); non-Hispanic Asian/Pacific Islander (including Asian Indian, Chinese, Filipina, Japanese, Korean, and Vietnamese); non-Hispanic Black; and non-Hispanic White. Main Outcomes and Measures: The primary outcomes were age-standardized rates of gestational diabetes (per 1000 live births) and respective mean annual percent change and rate ratios (RRs) of gestational diabetes in non-Hispanic Asian/Pacific Islander (overall and in subgroups), non-Hispanic Black, and Hispanic/Latina (overall and in subgroups) individuals relative to non-Hispanic White individuals (referent group). Results: Among the 12 610 235 included individuals (mean [SD] age, 26.3 [5.8] years), the overall age-standardized gestational diabetes rate significantly increased from 47.6 (95% CI, 47.1-48.0) to 63.5 (95% CI, 63.1-64.0) per 1000 live births from 2011 to 2019, a mean annual percent change of 3.7% (95% CI, 2.8%-4.6%) per year. Of the 12 610 235 participants, 21% were Hispanic/Latina (2019 gestational diabetes rate, 66.6 [95% CI, 65.6-67.7]; RR, 1.15 [95% CI, 1.13-1.18]), 8% were non-Hispanic Asian/Pacific Islander (2019 gestational diabetes rate, 102.7 [95% CI, 100.7-104.7]; RR, 1.78 [95% CI, 1.74-1.82]), 14% were non-Hispanic Black (2019 gestational diabetes rate, 55.7 [95% CI, 54.5-57.0]; RR, 0.97 [95% CI, 0.94-0.99]), and 56% were non-Hispanic White (2019 gestational diabetes rate, 57.7 [95% CI, 57.2-58.3]; referent group). Gestational diabetes rates were highest in Asian Indian participants (2019 gestational diabetes rate, 129.1 [95% CI, 100.7-104.7]; RR, 2.24 [95% CI, 2.15-2.33]). Among Hispanic/Latina participants, gestational diabetes rates were highest among Puerto Rican individuals (2019 gestational diabetes rate, 75.8 [95% CI, 71.8-79.9]; RR, 1.31 [95% CI, 1.24-1.39]). Gestational diabetes rates increased among all race and ethnicity subgroups and across all age groups. Conclusions and Relevance: Among individuals with a singleton first live birth in the US from 2011 to 2019, rates of gestational diabetes increased across all racial and ethnic subgroups. Differences in absolute gestational diabetes rates were observed across race and ethnicity subgroups.


Subject(s)
Diabetes, Gestational/ethnology , Adult , Cross-Sectional Studies , Female , Humans , Live Birth , Parity , Pregnancy , United States/epidemiology
16.
Res Pract Persons Severe Disabl ; 46(1): 53-60, 2021 Mar.
Article in English | MEDLINE | ID: mdl-37609517

ABSTRACT

In this article, we provide a case example of how telehealth can be used by care providers in their homes to access empirically validated procedures such as functional communication training. As shown in the case example, complex assessment and intervention procedures were implemented successfully by care providers in their homes while receiving real-time coaching by behavior analysts who were located in a hospital in a different city. This case example is representative of the results we obtained thus far; substantial improvements in challenging and adaptive behavior occurred. Given these results obtained to date with telehealth, in terms of both outcomes of interventions and rated acceptability of the procedures by care providers, further and more widespread application of telehealth is warranted.

17.
Am J Physiol Heart Circ Physiol ; 319(2): H331-H340, 2020 08 01.
Article in English | MEDLINE | ID: mdl-32589444

ABSTRACT

Mechanisms that contribute to myocardial fibrosis, particularly in response to left ventricular pressure overload (LVPO), remain poorly defined. To test the hypothesis that a myocardial-specific profile of secreted factors is produced in response to PO, levels of 44 factors implicated in immune cell recruitment and function were assessed in a murine model of cardiac hypertrophy and compared with levels produced in a model of pulmonary fibrosis (PF). Mice subjected to PO were assessed at 1 and 4 wk. Protein from plasma, LV, lungs, and kidneys were analyzed by specific protein array analysis in parallel with protein from mice subjected to silica-instilled PF. Of the 44 factors assessed, 13 proteins were elevated in 1-wk PO myocardium, whereas 18 proteins were found increased in fibrotic lung. Eight of those increased in 1-wk LVPO were not found to be increased in fibrotic lungs (CCL-11, CCL-12, CCL-17, CCL-19, CCL-21, CCL-22, IL-16, and VEGF). Additionally, six factors were increased in plasma of 1-wk LVPO in the absence of increases in myocardial levels. In contrast, in mice with PF, no factors were found increased in plasma that were not elevated in lung tissue. Of those factors increased at 1 wk, only TIMP-1 remained elevated at 4 wk of LVPO. Immunohistochemistry of myocardial vasculature at 1 and 4 wk revealed similar amounts of total vasculature; however, evidence of activated endothelium was observed at 1 wk and, to a lesser extent, at 4 wk LVPO. In conclusion, PO myocardium generated a unique signature of cytokine expression versus that of fibrotic lung.NEW & NOTEWORTHY Myocardial fibrosis and the resultant increases in myocardial stiffness represent pivotal consequences of chronic pressure overload (PO). In this study, cytokine profiles produced in a murine model of cardiac fibrosis induced by PO were compared with those produced in response to silica-induced lung fibrosis. A unique profile of cardiac tissue-specific and plasma-derived factors generated in response to PO are reported.


Subject(s)
Cytokines/blood , Hypertrophy, Left Ventricular/metabolism , Inflammation Mediators/blood , Lung/metabolism , Myocardium/metabolism , Pulmonary Fibrosis/metabolism , Ventricular Function, Left , Ventricular Remodeling , Animals , Disease Models, Animal , Female , Fibrosis , Hypertrophy, Left Ventricular/pathology , Hypertrophy, Left Ventricular/physiopathology , Lung/pathology , Male , Mice, Inbred C57BL , Myocardium/pathology , Pulmonary Fibrosis/pathology , Pulmonary Fibrosis/physiopathology
18.
Curr Diab Rep ; 20(3): 9, 2020 02 20.
Article in English | MEDLINE | ID: mdl-32080770

ABSTRACT

PURPOSE OF REVIEW: Type 2 diabetes is common, burdensome, and preventable. Landmark trials such as the Diabetes Prevention Program (DPP) demonstrated that resource-intensive lifestyle support interventions resulting in modest weight loss via healthy diet changes and physical activity can lower the rate of diabetes development by 58%. We performed a review of efforts to translate and implement DPP-like programs throughout the USA to identify challenges and opportunities for improvement. RECENT FINDINGS: For more than a decade, multiple stakeholders have worked to translate evidence-based principles of diabetes prevention to reach 84 million Americans with prediabetes. DPP-like programs have been delivered by over 1500 organizations, reaching almost 300,000 people, but this number represents less than 1% of the target population. Research has uncovered large gaps in efforts to diagnose, raise awareness, and provide access to DPP-like programs for adults with prediabetes, requiring further stakeholder engagement and coordination to resolve. Efforts to address prevailing gaps in diabetes prevention must address distinct and sometimes conflicting priorities and concerns of stakeholders. Our review recommends several areas of further research and action to improve type 2 diabetes prevention on a population scale.


Subject(s)
Diabetes Mellitus, Type 2/prevention & control , Prediabetic State/prevention & control , Adult , Exercise , Health Promotion , Humans , Life Style , Program Evaluation , Public Health , United States , Weight Loss
19.
Curr Diab Rep ; 20(2): 8, 2020 02 06.
Article in English | MEDLINE | ID: mdl-32030514

ABSTRACT

PURPOSE OF REVIEW: Community health centers (CHCs) provide care to millions of vulnerable patients in the USA, including a disproportionate number with diabetes. Policies affecting diabetes management in CHCs therefore have broad implications for clinical practice and patient outcomes nationwide. We describe prior policies that have influenced diabetes management in CHCs, discuss current policies and programs, as well as present emerging innovations and future directions for diabetes care in this setting. RECENT FINDINGS: Domains for current diabetes policies and programs in CHCs include coverage requirements, quality reporting and incentives, prescription discounts, healthy behavior incentives, and team-based care. Policies in these areas affect the management of diabetes at multiple levels, from organizations that support CHCs to individual health centers, and the providers and patients based there. Several domains of interrelated policies and programs impact CHC diabetes management at multiple levels. Stakeholders' understanding of these policies and programs may identify opportunities to improve diabetes care.


Subject(s)
Community Health Centers , Diabetes Mellitus/therapy , Health Policy , Disease Management , Humans , Quality of Health Care , Social Determinants of Health , Telemedicine
20.
J Paediatr Child Health ; 56(4): 636-641, 2020 Apr.
Article in English | MEDLINE | ID: mdl-31821679

ABSTRACT

AIM: This study describes an Australian cohort of paediatric Buruli ulcer (BU) patients and compares them with adult BU patients. METHODS: Analysis of a prospective cohort of all BU cases managed at Barwon Health, Victoria, from 1 January 1998 to 31 May 2018 was performed. Children were defined as ≤15 years of age. RESULTS: A total of 565 patients were included: 52 (9.2%) children, 289 (51.2%) adults aged 16-64 years and 224 (39.6%) adults aged ≥65 years. Among children, half were female and the median age was 8.0 years (interquartile range 4.8-12.3 years). Six (11.5%) cases were diagnosed from 2001 to 2006, 14 (26.9%) from 2007 to 2012 and 32 (61.5%) from 2013 to 2018. Compared to adults, children had a significantly higher proportion of non-ulcerative lesions (32.7%, P < 0.001) and a higher proportion of severe lesions (26.9%, P < 0.01). The median duration of symptoms prior to diagnosis was shorter for children compared with adults aged 16-64 years (42 vs. 56 days, P = 0.04). Children were significantly less likely to experience antibiotic complications (6.1%) compared with adults (20.6%, P < 0.001), but had a significantly higher rate of paradoxical reactions (38.8%) compared with adults aged 16-64 (19.2%) (P < 0.001). Paradoxical reactions in children occurred significantly earlier than in adults (median 17 vs. 56 days, P < 0.01). Cure rates were similarly high for children compared to adults treated with antibiotics alone or with antibiotics and surgery. CONCLUSIONS: Paediatric BU cases in Australia are increasing and represent an important but stable proportion of Australian BU cohorts. Compared with adults, there are significant differences in clinical presentation and treatment outcomes.


Subject(s)
Buruli Ulcer , Mycobacterium ulcerans , Adolescent , Adult , Aged , Anti-Bacterial Agents/therapeutic use , Buruli Ulcer/diagnosis , Buruli Ulcer/drug therapy , Buruli Ulcer/epidemiology , Child , Child, Preschool , Female , Humans , Male , Middle Aged , Prospective Studies , Victoria/epidemiology , Young Adult
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