Developmental impact of glutamate transporter overexpression on dopaminergic neuron activity and stereotypic behavior.

Obsessive-compulsive disorder (OCD) is a disabling condition that often begins in childhood. Genetic studies in OCD have pointed to SLC1A1, which encodes the neuronal glutamate transporter EAAT3, with evidence suggesting that increased expression contributes to risk. In mice, midbrain Slc1a1 expression supports repetitive behavior in response to dopaminergic agonists, aligning with neuroimaging and pharmacologic challenge studies that have implicated the dopaminergic system in OCD. These findings suggest that Slc1a1 may contribute to compulsive behavior through altered dopaminergic transmission; however, this theory has not been mechanistically tested. To examine the developmental impact of Slc1a1 overexpression on compulsive-like behaviors, we, therefore, generated a novel mouse model to perform targeted, reversible overexpression of Slc1a1 in dopaminergic neurons. Mice with life-long overexpression of Slc1a1 showed a significant increase in amphetamine (AMPH)-induced stereotypy and hyperlocomotion. Single-unit recordings demonstrated that Slc1a1 overexpression was associated with increased firing of dopaminergic neurons. Furthermore, dLight1.1 fiber photometry showed that these behavioral abnormalities were associated with increased dorsal striatum dopamine release. In contrast, no impact of overexpression was observed on anxiety-like behaviors or SKF-38393-induced grooming. Importantly, overexpression solely in adulthood failed to recapitulate these behavioral phenotypes, suggesting that overexpression during development is necessary to generate AMPH-induced phenotypes. However, doxycycline-induced reversal of Slc1a1/EAAT3 overexpression in adulthood normalized both the increased dopaminergic firing and AMPH-induced responses. These data indicate that the pathologic effects of Slc1a1/EAAT3 overexpression on dopaminergic neurotransmission and AMPH-induced stereotyped behavior are developmentally mediated, and support normalization of EAAT3 activity as a potential treatment target for basal ganglia-mediated repetitive behaviors.

Increased circulating cytokine levels in African American women with obesity and elevated HbA1c.

PURPOSE: Obesity has emerged as one of the biggest health crisis and is the leading cause of death and disabilities around the world. BMI trends suggest that majority of the increase in T2D is resulting from the increased prevalence of obesity. In fact, 85.2% of people with T2D are overweight or obese. The highest prevalence for obesity is seen in non-Hispanic, African American women (56.6%). T2D is classified as an inflammatory disease because of elevated, circulating pro-inflammatory cytokines and acute-phase inflammatory proteins. This study was designed to determine how high HbA1c and serum glucose correlate with circulatory cytokine levels in obese, African American women. METHODS: We investigated cytokine/chemokine serum levels using a multiplex assay. Then we used Pairwise Pearson Correlation Test to determine the relationship between clinical metabolic parameters and cytokine/chemokine serum levels. RESULTS: The results indicated that participants with elevated HbA1c exhibited an up regulation of IL-3, IL-4, IL-7, TNF-α, IFN-α2 and CX3CL1 serum levels compared to participants with normal HbA1c. These cytokines were also correlated with several clinical metabolic parameters. CONCLUSIONS: The results suggest that IL-3, IL-4, IL-7, TNF-α, IFN-α2 and CX3CL1 serum levels may contribute to the development and onset of type 2 diabetes.

Review of Postoperative Delirium in Geriatric Patients After Hip Fracture Treatment.

Introduction: Postoperative delirium (POD) is a serious complication occurring in 4-53.3% of geriatric patients undergoing surgeries for hip fracture. Incidence of hip fractures is projected to grow 11.9% from 258,000 in 2010 to 289,000 in 2030 based on 1990 to 2010 data. As prevalence of hip fractures is projected to increase, POD is also anticipated to increase. Signficance: Postoperative delirium remains the most common complication of emergency hip fracture surgery leading to high morbidity and mortality rates despite significant research conducted regarding this topic. This study reviews literature from 1990 to 2021 regarding POD in geriatric hip fracture management. Results: Potentially modifiable and non-modifiable risk factors for developing POD include, but are not limited to, male gender, older age, multiple comorbidities, specific comorbidities (dementia, cognitive impairment, diabetes, vision impairment, and abnormal blood pressure), low BMI, preoperative malnutrition, low albumin, low hematocrit, blunted preoperative cytokines, emergency surgery, time to admission and surgery, preoperative medical treatment, polypharmacy, delirium-inducing medications, fever, anesthesia time, and sedation depth and type. Although the pathophysiology remains unclear, the leading theories suggest neurotransmitter imbalance, inflammation, and electrolyte or metabolic derangements as the underlying cause of POD. POD is associated with increased length of hospital stay, cost, morbidity, and mortality. Prevention and early recognition are key factors in managing POD. Methods to reduce POD include utilizing interdisciplinary teams, educational programs for healthcare professionals, reducing narcotic use, avoiding delirium-inducing medications, and multimodal pain control. Conclusion: While POD is a known complication after hip fracture surgery, further exploration in prevention is needed. Early identification of risk factors is imperative to prevent POD in geriatric patients. Early prevention will enhance delivery of health care both pre- and post-operatively leading to the best possible surgical outcome and better quality of life after hip fracture treatment.

What Does Your PROMIS Score Mean? Improving the Utility of Patient-Reported Outcomes at the Point of Care.

STUDY DESIGN: Prospective cohort. OBJECTIVES: Patient-Reported Outcome Measurement Information System (PROMIS) has been validated for lumbar spine. Use of patient-reported outcome (PRO) measures can improve clinical decision making and health literacy at the point of care. Use of PROMIS, however, has been limited in part because clinicians and patients lack plain language understanding of the meaning of scores and it remains unclear how best to use them at the point of care. The purpose was to develop plain language descriptions to apply to PROMIS Physical Function (PF) and Pain Interference (PI) scores and to assess patient understanding and preferences in presentation of their individualized PRO information. METHODS: Retrospective analysis of prospectively collected PROMIS PF v1.2 and PI v1.1 for patients presenting to a tertiary spine center for back/lower extremity complaints was performed. Patients with missing scores, standard error >0.32, and assessments with <4 or >12 questions were excluded. Scores were categorized into score groups, specifically PROMIS PF groups were: <18, 20 ± 2, 25 ± 2, 30 ± 2, 35 ± 2, 40 ± 2, 45 ± 2, 50 ± 2, 55 ± 2, 60 ± 2, and >62; and PROMIS PI groups were: <48, 50 ± 2, 55 ± 2, 60 ± 2, 65 ± 2, 70 ± 2, 75 ± 2, 80 ± 2, and >82. Representative questions and answers from the PROMIS PI and PROMIS PF were selected for each score group, where questions with <25 assessments or representing <15% of assessments were excluded. Two fellowship-trained spine surgeons further trimmed the questions to create a streamlined clinical tool using a consensus process. Plain language descriptions for PROMIS PF were then used in a prospective assessment of 100 consecutive patients. Patient preference for consuming the score data was recorded and analyzed. RESULTS: In total, 12 712 assessments/5524 unique patients were included for PF and 14 823 assessments/6582 unique patients for PI. More than 90% of assessments were completed in 4 questions. The number of assessments and patients per scoring group were normally distributed. The mean PF score was 37.2 ± 8.2 and the mean PI was 63.3 ± 7.4. Plain language descriptions and compact clinical tool was were generated. Prospectively 100 consecutive patients were surveyed for their preference in receiving their T-score versus plain language description versus graphical presentation. A total of 78% of patients found receiving personalized PRO data helpful, while only 1% found this specifically not helpful. Overall, 80% of patients found either graphical or plain language more helpful than T-score alone, and half of these preferred plain language and graphical descriptions together. In total, 89% of patients found the plain language descriptions to be accurate. CONCLUSIONS: Patients at the point of care are interested in receiving the results of their PRO measures. Plain language descriptions of PROMIS scores enhance patient understanding of PROMIS numerical scores. Patients preferred plain language and/or graphical representation rather than a numerical score alone. While PROs are commonly used for assessing outcomes in research, use at point of care is a growing interest and this study clarifies how they might be utilized in physician-patient communication.

Serum miR-17 levels are downregulated in obese, African American women with elevated HbA1c.

PURPOSE: Type 2 diabetes is heterogeneous disease characterized by several conditions including hyperglycemia. It is estimated that over 350 million people worldwide are suffering from type 2 diabetes and this number is expected to rise. According to the CDC, African Americans were observed to have a 40% higher incidence of diabetes compared to European Americans. Epigenetic modulating mechanisms such as microRNAs (miRNAs), have recently been established as a massive regulatory machine in metabolic syndrome, obesity and type 2 diabetes. In the present study, we aimed to investigate the serum levels of circulating miRNA 17 (miR-17) of obese, African American women with elevated HbA1c. METHODS: We investigated miR-17 serum levels using qPCR. Then we used Pairwise Pearson Correlation Test to determine the relationship between clinical metabolic parameters and miR-17 serum levels. RESULTS: The results indicated that participants with elevated HbA1c exhibited a down regulation of serum miR-17 levels compared to participants with normal HbA1c. MiR-17 was also correlated with serum calcium in participants with normal HbA1c. CONCLUSIONS: The results suggest that serum miR-17 is involved in the regulation of glucose and calcium homeostasis, which may contribute to the development of type 2 diabetes.

Improving the school food environment: results from a pilot study in middle schools.

Our objective for this study was to examine the feasibility of instituting environmental changes during a 6-week pilot in school foodservice programs, with long-term goals of improving dietary quality and preventing obesity and type 2 diabetes in youth. Participants included students and staff from six middle schools in three states. Formative assessment with students and school staff was conducted in the spring of 2003 to inform the development of school foodservice policy changes. Thirteen potential policy goals were delineated. These formed the basis for the environmental change pilot intervention implemented during the winter/spring of 2004. Questionnaires were used to assess the extent to which the 13 foodservice goals were achieved. Success was defined as achieving 75% of goals not met at baseline. Daily data were collected on goal achievement using the schools' daily food production and sales records. Qualitative data were also collected after the pilot study to obtain feedback from students and staff. Formative research with staff and students identified potential environmental changes. Most schools made substantial changes in the National School Lunch Program meal and snack bar/a la carte offerings. Vending goals were least likely to be achieved. Only one school did not meet the 75% goal achievement objective. Based on the objective data as well as qualitative feedback from student focus groups and interviews with students and school staff, healthful school foodservice changes in the cafeteria and snack bar can be implemented and were acceptable to the staff and students. Implementing longer-term and more ambitious changes and assessing cost issues and the potential enduring impact of these changes on student dietary change and disease risk reduction merits investigation.

Changing our future: obesity and the metabolic syndrome in children and adolescents.

Obesity, or overweight, in childhood is a major risk factor for the metabolic syndrome in adolescence, as the prevalence in US children tripled between 1970 and 2000. An increase in the metabolic syndrome in youth has followed this increase. In population-based studies, the prevalence of the syndrome ranged from 3.6% to 4.2%. In smaller studies with many overweight youth, the prevalence was 28.7% to 39.7% in those who were overweight and 49.7% in those who were severely obese. Overweight children are likely to have hyperinsulinemia, high-density lipoprotein cholesterol, high triglycerides, and hypertension, which are components of the metabolic syndrome. Nurses have an important role in screening for these metabolic syndrome components. Screening is especially important in boys and girls who are overweight and in girls with early menarche. A problem when screening children and adolescents is determining normative values, but guidelines are available. Prevention and management of the metabolic syndrome are not specific to the syndrome, but rather should be focused on the underlying problem of overweight and related problems that comprise the syndrome. We must use all avenues available to us, including influencing public and school policies, and pay close attention to overweight and metabolic syndrome components in our clinical practice, whether with children or adults. Preventing and managing the metabolic syndrome should be a family matter, and the necessary lifestyle changes will benefit the entire family.

Assessment of public health risks associated with atmospheric exposure to PM2.5 in Washington, DC, USA.

In this research, we investigated the public health risks associated with atmospheric exposure to PM2.5 for different subpopulations (black, white, Hispanic, youth, adults, and elderly) in the Washington, DC area. Washington, DC has long been considered a non-healthy place to live according to the American Lung Association due to its poor air quality. This recognition clearly includes the negative PM-related human health effects within the region. Specifically, DC fine particulate matter (PM2.5) [or particulate matter with an aerodynamic diameter less than 2.5 microm] poses notable health risks to subpopulations having an annual mean value of 16.70 microg/m(3) during the years 1999-2004, exceeding the EPA National Ambient Air Quality Standard (NAAQS) of 15 microg/m(3). Incessant exposure to significant levels of PM has previously been linked to deleterious health effects, such as heart and lung diseases. The environmental quality and public health statistics of Washington, DC indicate the need for higher-resolution measurements of emissions, both spatially and temporally, and increased analysis of PM-related health effects. Our findings show that there are significant risks of ward-specific pediatric asthma emergency room visits (ERV). Results also illustrate lifetime excess lung cancer risks, exceeding the 1 x 10(-6) threshold for the measured levels of particulate matter and heavy metals (chromium and arsenic) on behalf of numerous subpopulations in the DC selected wards.

Evidence for environmental contamination in residential neighborhoods surrounding the defense depot of Memphis, Tennessee.

An interdisciplinary environmental assessment team from the Howard University Environmental Justice Partnership (HUEJP) conducted a site visit and assessment of the Defense Depot of Memphis, Tennessee in February of 2000. This depot was built in the late 1940's for storage of numerous chemicals and munitions. As the years progressed, many Memphis citizens have grown to believe that the activities and chemical stockpile located at this site have negatively affected the health environment of their residents. There is anecdotal evidence and documentation of numerous cancers and other illnesses in those local territories, and specifically, at the Memphis Depot site. Currently, this depot is closed and in remediation by the local government. Particularly, citizens of the Rozelle community have started a campaign to investigate any signs of exposure pathways to noted health risks. The HUEJP was contacted and asked to investigate the community concerns. Obliging to the request, we aimed to sample at three drainage sites and a residential site, talk to local citizens, and gain any additional information that would be helpful in relieving anxiety in the Rozelle community. Soil, sediment, and water samples were collected and analyzed for total organic carbon, inorganic anions, and heavy metals. These data show that for the four sites sampled, the highest concentrations of organic compounds and heavy metals were located either within a residential area or in an area with a direct transport pathway to the community. Atomic absorption analysis revealed detectable amounts of cadmium, lead and chromium metals at all sites with direct transport pathways into the residential community, with chromium concentrations being far in excess of the EPA standard limits.

Gender differences in preclinical markers of kidney injury in a rural north Carolina african-american cohort.

INTRODUCTION: The incidence rate of end-stage renal disease (ESRD) is highest among African-American (AA) males. The reason for this disparity in ESRD for AA males remains unclear, but it is well established that diabetes is the leading risk factor. Prediabetes may also be a risk for kidney disease since prediabetics have increased risk for cardiovascular disease and often do not receive drug interventions unless their hemoglobin A1c (A1c) level is above 6%. Perhaps, AA males are at greater risk because they often are untreated prediabetics and this predisposes them to renal injury. Therefore, we hypothesize that prediabetic AA males have higher albumin:creatinine ratio (ACr), a biomarker of renal injury, than their female counterparts. METHODS: Male and female AAs were recruited (53 females and 47 males; 45 ± 2 years old) from a rural northeastern region of NC. Blood and urine samples were collected for A1c and albumin measurements, respectively. Participants were stratified based on their A1c levels: non-diabetic: <5.7%, prediabetic: ≥5.7% but <6.5%, and diabetic: ≥6.5%. RESULTS: The proportion of males that are normal, prediabetic, and diabetic differed from that of females (p = 0.002). Interestingly, prediabetic men tended to be younger (41 ± 4 vs. 51 ± 3, respectively; p = 0.027) than prediabetic females (p = 0.027). A1c and ACr were not associated with blood pressure in males or females. AA males had a relative risk of 0.9, 2.5, and 1.4 for microalbuminuria for non-diabetic, prediabetic, and diabetic, respectively, compared to AA females. CONCLUSION: These results support our hypothesis that AA males may be predisposed to prediabetes kidney injury compared to their female counterpart. Thus, young AA males should be screened for biomarkers of kidney injury even if they have normal glucose and blood pressure levels.

Association of study characteristics with estimates of effect size in studies of ecstasy use.

Studies of the chronic effects of MDMA, or 'ecstasy', in humans have been largely inconsistent. We explored whether study-level characteristics are associated with the effect size estimate reported. We based our analyses on the recent systematic review by Rogers and colleagues, focusing on those meta-analyses within this report where there was a relatively large number of studies contributing to each individual meta-analysis. Linear regression was used to investigate the association between study level variables and effect size estimate, weighted by the inverse of the SE of the effect size estimate, with cluster correction for studies which contributed multiple estimates. This indicated an association between effect size estimate and both user group, with smaller estimates among studies recruiting former users compared with those recruiting current users, and control group, with smaller estimates among studies recruiting polydrug user controls compared with those recruiting drug-naïve controls. In addition, increasing year of publication was associated with reduced effect size estimate, and there was a trend level association with prevalence of ecstasy use, reflecting smaller estimates among studies conducted in countries with higher prevalence of ecstasy use. Our data suggest a number of study-level characteristics which appear to influence individual study effect size estimates. These should be considered when designing future studies, and also when interpreting the ecstasy literature as a whole.