A patient-centered comparative effectiveness research study of culturally appropriate options for diabetes self-management.

This project compared the effectiveness of two evidence-based models of culturally competent diabetes health promotion: The Diabetes Self-Management Support Empowerment Model (DSMS), and The Chronic Care Model (CCM). Our primary outcome was improvement in patient capacity for diabetes self-management as measured by the Diabetes Knowledge Questionnaire (DKQ) and the Patient Activation Measure (PAM). Our secondary outcome was patient success at diabetes self-management as measured by improvement in A1c, depression sores using the PHQ-9, and Body Mass Index (BMI). We also gathered data on the cultural competence of the program using the Consumer Assessment of Healthcare Providers and Systems Cultural Competence Set (CAHPS-CC). We compared patient outcomes in two existing sites in Albuquerque, New Mexico that serve a large population of Latino diabetes patients from low-income households. Participants were enrolled as dyads-a patient participant (n=226) and a social support participant (n=226). Outcomes over time and by program were analyzed using longitudinal linear mixed modeling, adjusted for patient participant demographic characteristics and other potential confounding covariates. Secondary outcomes were also adjusted for potential confounders. Interactions with both time and program helped to assess outcomes. This study did not find a difference between the two sites with respect to the primary outcome measures and only one of the three secondary outcomes showed differential results. The main difference between programs was that depression decreased more for CCM than for DSMS. An exploratory, subgroup analysis revealed that at CCM, patient participants with a very high A1c (>10) demonstrated a clinically meaningful decrease. However, given the higher cultural competence rating for the CCM, statistically significant improvement in depression, and the importance of social support to the patients, results suggest that a culturally and contextually situated diabetes self-management and education program design may deliver benefit for patients, especially for patients with higher A1c levels.

Association Between Patient Factors and the Effectiveness of Wearable Trackers at Increasing the Number of Steps per Day Among Adults With Cardiometabolic Conditions: Meta-analysis of Individual Patient Data From Randomized Controlled Trials.

BACKGROUND: Current evidence supports the use of wearable trackers by people with cardiometabolic conditions. However, as the health benefits are small and confounded by heterogeneity, there remains uncertainty as to which patient groups are most helped by wearable trackers. OBJECTIVE: This study examined the effects of wearable trackers in patients with cardiometabolic conditions to identify subgroups of patients who most benefited and to understand interventional differences. METHODS: We obtained individual participant data from randomized controlled trials of wearable trackers that were conducted before December 2020 and measured steps per day as the primary outcome in participants with cardiometabolic conditions including diabetes, overweight or obesity, and cardiovascular disease. We used statistical models to account for clustering of participants within trials and heterogeneity across trials to estimate mean differences with the 95% CI. RESULTS: Individual participant data were obtained from 9 of 25 eligible randomized controlled trials, which included 1481 of 3178 (47%) total participants. The wearable trackers revealed that over the median duration of 12 weeks, steps per day increased by 1656 (95% CI 918-2395), a significant change. Greater increases in steps per day from interventions using wearable trackers were observed in men (interaction coefficient -668, 95% CI -1157 to -180), patients in age categories over 50 years (50-59 years: interaction coefficient 1175, 95% CI 377-1973; 60-69 years: interaction coefficient 981, 95% CI 222-1740; 70-90 years: interaction coefficient 1060, 95% CI 200-1920), White patients (interaction coefficient 995, 95% CI 360-1631), and patients with fewer comorbidities (interaction coefficient -517, 95% CI -1188 to -11) compared to women, those aged below 50, non-White patients, and patients with multimorbidity. In terms of interventional differences, only face-to-face delivery of the tracker impacted the effectiveness of the interventions by increasing steps per day. CONCLUSIONS: In patients with cardiometabolic conditions, interventions using wearable trackers to improve steps per day mostly benefited older White men without multimorbidity. TRIAL REGISTRATION: PROSPERO CRD42019143012; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=143012.

Evidence-based practice strategies for faculty professional development in clinical translational research at Institutional Development Award (IDeA) state institutions in the Mountain West.

The Mountain West Clinical Translational Research - Infrastructure Network (MW CTR-IN), established in 2013, is a research network of 13 university partners located among seven Institutional Development Award (IDeA) states targeting health disparities. This is an enormous undertaking because of the size of the infrastructure network (encompassing a third of the US landmass and spanning four time zones in predominantly rural and underserved areas, with populations that have major health disparities issues). In this paper, we apply the barriers, strategies, and metrics to an adapted educational conceptual model by Fink (2013). Applying this model, we used four tailored approaches across this regional infrastructure network to: (1) assess individual faculty specific needs, (2) reach out and engage with faculty, (3) provide customized services to meet the situational needs of faculty, and (4) utilize a "closed communication feedback loop" between Professional Development (PD) core and MW CTR-IN faculty within the context of their home institutional environment. Summary statement results from participating faculty show that these approaches were positive. Grounded in best educational practice approaches, we have an opportunity to refine and build from this sound foundation with implications for future use in other CTR-IN networks and institutions in the IDeA states.

The associations between COVID-19 diagnosis, type 1 diabetes, and the risk of diabetic ketoacidosis: A nationwide cohort from the US using the Cerner Real-World Data.

OBJECTIVE: To assess the risk of new-onset type 1 diabetes mellitus (T1D) diagnosis following COVID-19 diagnosis and the impact of COVID-19 diagnosis on the risk of diabetic ketoacidosis (DKA) in patients with prior T1D diagnosis. RESEARCH DESIGN AND METHODS: Retrospective data consisting of 27,292,879 patients from the Cerner Real-World Data were used. Odds ratios, overall and stratified by demographic predictors, were calculated to assess associations between COVID-19 and T1D. Odds ratios from multivariable logistic regression models, adjusted for demographic and clinical predictors, were calculated to assess adjusted associations between COVID-19 and DKA. Multiple imputation with multivariate imputation by chained equations (MICE) was used to account for missing data. RESULTS: The odds of developing new-onset T1D significantly increased in patients with COVID-19 diagnosis (OR: 1.42, 95% CI: 1.38, 1.46) compared to those without COVID-19. Risk varied by demographic groups, with the largest risk among pediatric patients ages 0-1 years (OR: 6.84, 95% CI: 2.75, 17.02) American Indian/Alaskan Natives (OR: 2.30, 95% CI: 1.86, 2.82), Asian or Pacific Islanders (OR: 2.01, 95% CI: 1.61, 2.53), older adult patients ages 51-65 years (OR: 1.77, 95% CI: 1.66, 1.88), those living in the Northeast (OR: 1.71, 95% CI: 1.61, 1.81), those living in the West (OR: 1.65, 95% CI: 1.56, 1.74), and Black patients (OR: 1.59, 95% CI: 1.47, 1.71). Among patients with diagnosed T1D at baseline (n = 55,359), 26.7% (n = 14,759) were diagnosed with COVID-19 over the study period. The odds of developing DKA for those with COVID-19 were significantly higher (OR 2.26, 95% CI: 2.04, 2.50) than those without COVID-19, and the largest risk was among patients with higher Elixhauser Comorbidity Index. CONCLUSIONS: COVID-19 diagnosis is associated with significantly increased risk of new-onset T1D, and American Indian/Alaskan Native, Asian/Pacific Islander, and Black populations are disproportionately at risk. In patients with pre-existing T1D, the risk of developing DKA is significantly increased following COVID-19 diagnosis.

Preoperative vitamin D deficiency is associated with increased risk of postoperative hypocalcemia after total thyroidectomy.

Prior single-institution studies suggest that preoperative vitamin D deficiency (VDD) is associated with postoperative hypocalcemia and a prolonged length of hospital stay following total thyroidectomy. In this study, we employ a multi-institutional, de-identified electronic health records database to address this issue. We hypothesize that total thyroidectomy patients with preoperative VDD will be at an increased associated risk of postoperative hypocalcemia and hospitalization. Using Cerner Health Facts, we identified 2447 patients who underwent total or subtotal thyroidectomy between 2008 and 2016 and who had a documented 25-hydroxyvitamin D concentration obtained within 12 months of the surgery date using International Classification of Diseases 9/10, Current Procedural Terminology and Healthcare Common Procedure Coding System codes. Data from 984 patients who underwent total thyroidectomy were analyzed. Analysis of variance models estimated the effect of VDD on postoperative numerical variables. Multiple logistic regression estimated the risk of postoperative hypocalcemia and hospital stay, adjusting for any imbalanced demographic variables and operative characteristics. On average, postoperative total calcium concentrations in the VDD group were lower by 0.3 mg/dL compared with that of the non-VDD group (p<0.01). The risk of postoperative hypocalcemia was 2.2 times higher in the VDD group compared with the non-VDD group (p<0.01). Although the length of hospital stay after thyroidectomy was longer in the VDD group compared with the non-VDD group (p=0.03), VDD is not an independent risk factor for prolonged hospitalization following thyroidectomy (p=0.13). VDD is associated with a higher risk of hypocalcemia following total thyroidectomy. Prethyroidectomy operative screening for VDD should be considered.

Diabetic Peripheral Neuropathy Risk Assessment using Digital Fundus Photographs and Machine Learning.

In this work, we demonstrate a novel approach to assessing the risk of Diabetic Peripheral Neuropathy (DPN) using only the retinal images of the patients. Our methodology consists of convolutional neural network feature extraction, dimensionality reduction and feature selection with random projections, combination of image features to case-level representations, and the training and testing of a support vector machine classifier. Using clinical diagnosis as ground truth for DPN, we achieve an overall accuracy of 89% on a held-out test set, with sensitivity reaching 78% and specificity reaching 95%.

AMPK is activated during lysosomal damage via a galectin-ubiquitin signal transduction system.

Lysosomal damage activates AMPK, a regulator of macroautophagy/autophagy and metabolism, and elicits a strong ubiquitination response. Here we show that the cytosolic lectin LGALS9 detects lysosomal membrane breach by binding to lumenal glycoepitopes, and directs both the ubiquitination response and AMPK activation. Proteomic analyses have revealed increased LGALS9 association with lysosomes, and concomitant changes in LGALS9 interactions with its newly identified partners that control ubiquitination-deubiquitination processes. An LGALS9-inetractor, deubiquitinase USP9X, dissociates from damaged lysosomes upon recognition of lumenal glycans by LGALS9. USP9X's departure from lysosomes promotes K63 ubiquitination and stimulation of MAP3K7/TAK1, an upstream kinase and activator of AMPK hitherto orphaned for a precise physiological function. Ubiquitin-activated MAP3K7/TAK1 controls AMPK specifically during lysosomal injury, caused by a spectrum of membrane-damaging or -permeabilizing agents, including silica crystals, the intracellular pathogen Mycobacterium tuberculosis, TNFSF10/TRAIL signaling, and the anti-diabetes drugs metformin. The LGALS9-ubiquitin system activating AMPK represents a novel signal transduction system contributing to various physiological outputs that are under the control of AMPK, including autophagy, MTOR, lysosomal maintenance and biogenesis, immunity, defense against microbes, and metabolic reprograming. ABBREVIATIONS: AMPK: AMP-activated protein kinase; APEX2: engineered ascorbate peroxidase 2; ATG13: autophagy related 13; ATG16L1: autophagy related 16 like 1; BMMs: bone marrow-derived macrophages; CAMKK2: calcium/calmodulin dependent protein kinase kinase 2; DUB: deubiquitinase; GPN: glycyl-L-phenylalanine 2-naphthylamide; LLOMe: L-leucyl-L-leucine methyl ester; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MAP3K7/TAK1: mitogen-activated protein kinase kinase kinase 7; MERIT: membrane repair, removal and replacement; MTOR: mechanistic target of rapamycin kinase; STK11/LKB1: serine/threonine kinase 11; TNFSF10/TRAIL: TNF superfamily member 10; USP9X: ubiquitin specific peptidase 9 X-linked.

AMPK, a Regulator of Metabolism and Autophagy, Is Activated by Lysosomal Damage via a Novel Galectin-Directed Ubiquitin Signal Transduction System.

AMPK is a central regulator of metabolism and autophagy. Here we show how lysosomal damage activates AMPK. This occurs via a hitherto unrecognized signal transduction system whereby cytoplasmic sentinel lectins detect membrane damage leading to ubiquitination responses. Absence of Galectin 9 (Gal9) or loss of its capacity to recognize lumenal glycans exposed during lysosomal membrane damage abrogate such ubiquitination responses. Proteomic analyses with APEX2-Gal9 have revealed global changes within the Gal9 interactome during lysosomal damage. Gal9 association with lysosomal glycoproteins increases whereas interactions with a newly identified Gal9 partner, deubiquitinase USP9X, diminishes upon lysosomal injury. In response to damage, Gal9 displaces USP9X from complexes with TAK1 and promotes K63 ubiquitination of TAK1 thus activating AMPK on damaged lysosomes. This triggers autophagy and contributes to autophagic control of membrane-damaging microbe Mycobacterium tuberculosis. Thus, galectin and ubiquitin systems converge to activate AMPK and autophagy during endomembrane homeostasis.

Hypothyroidism, Sex, and Age Predict Future Thromboembolic Events Among Younger People.

PURPOSE: Aberrant thyroid function causes dysregulated metabolic homeostasis. Literature has demonstrated hypercoagulability in hypothyroidism, suggesting a risk for thromboembolic events (TEE). We hypothesize that individuals with hypothyroidism will experience more clinically-diagnosed TEE than euthyroid individuals. METHODS: De-identified patient data from the University of New Mexico Health Sciences Center were retrieved using thyrotropin (TSH; thyroid-stimulating hormone) for case-finding from 2005 to 2007 and ICD billing codes to identify TEE during the follow-up period of 10 to 12 years. Diagnoses affecting coagulation were excluded and 12 109 unique enrollees were categorized according to TSH concentration as Hyperthyroid (n = 510), Euthyroid (n = 9867), Subclinical Hypothyroid (n = 1405), or Overtly Hypothyroid (n = 327). Analysis with multiple logistic regression provided the odds of TEE while adjusting for covariates. RESULTS: There were 228 TEEs in the cohort over 5.1 ±â€…4.3 years of follow-up. Risk of TEE varied significantly across study groups while adjusting for sex, race/ethnicity, levothyroxine, oral contraceptive therapy, and visit status (outpatient vs non-outpatient), and this risk was modified by age. Overt Hypothyroidism conferred a significantly higher risk of TEE than Euthyroidism below age 35, and Hyperthyroidism conferred an increased risk for TEE at age 20. Analysis also demonstrated a higher age-controlled risk for a subsequent TEE in men compared with women (odds ratio [OR] = 1.36; 95% confidence interval [CI], 1.02-1.81). Subanalysis of smoking status (n = 5068, 86 TEE) demonstrated that smokers have 2.21-fold higher odds of TEE relative to nonsmokers (95% CI, 1.41-3.45). CONCLUSIONS: In this retrospective cohort study, Overt Hypothyroidism conferred increased risk of TEE over the next decade for individuals younger than 35 years of age, as compared with Euthyroidism.

Characterizing health researcher barriers to sharing results with study participants.

INTRODUCTION: Research participants want to receive results from studies in which they participate. However, health researchers rarely share the results of their studies beyond scientific publication. Little is known about the barriers researchers face in returning study results to participants. METHODS: Using a mixed-methods design, health researchers (N = 414) from more than 40 US universities were asked about barriers to providing results to participants. Respondents were recruited from universities with Clinical and Translational Science Award programs and Prevention Research Centers. RESULTS: Respondents reported the percent of their research where they experienced each of the four barriers to disseminating results to participants: logistical/methodological, financial, systems, and regulatory. A fifth barrier, investigator capacity, emerged from data analysis. Training for research faculty and staff, promotion and tenure incentives, and funding agencies supporting dissemination of results to participants were solutions offered to overcoming barriers. CONCLUSIONS: Study findings add to literature on research dissemination by documenting health researchers' perceived barriers to sharing study results with participants. Implications for policy and practice suggest that additional resources and training could help reduce dissemination barriers and increase the return of results to participants.

Autophagy, Inflammation, and Metabolism (AIM) Center in its second year.

The NIH-funded center for autophagy research named Autophagy, Inflammation, and Metabolism (AIM) Center of Biomedical Research Excellence, located at the University of New Mexico Health Science Center is now completing its second year as a working center with a mission to promote autophagy research locally, nationally, and internationally. The center has thus far supported a cadre of 6 junior faculty (mentored PIs; mPIs) at a near-R01 level of funding. Two mPIs have graduated by obtaining their independent R01 funding and 3 of the remaining 4 have won significant funding from NIH in the form of R21 and R56 awards. The first year and a half of setting up the center has been punctuated by completion of renovations and acquisition and upgrades for equipment supporting autophagy, inflammation and metabolism studies. The scientific cores usage, and the growth of new studies is promoted through pilot grants and several types of enablement initiatives. The intent to cultivate AIM as a scholarly hub for autophagy and related studies is manifested in its Vibrant Campus Initiative, and the Tuesday AIM Seminar series, as well as by hosting a major scientific event, the 2019 AIM symposium, with nearly one third of the faculty from the International Council of Affiliate Members being present and leading sessions, giving talks, and conducting workshop activities. These and other events are often videostreamed for a worldwide scientific audience, and information about events at AIM and elsewhere are disseminated on Twitter and can be followed on the AIM web site. AIM intends to invigorate research on overlapping areas between autophagy, inflammation and metabolism with a number of new initiatives to promote metabolomic research. With the turnover of mPIs as they obtain their independent funding, new junior faculty are recruited and appointed as mPIs. All these activities are in keeping with AIM's intention to enable the next generation of autophagy researchers and help anchor, disseminate, and convey the depth and excitement of the autophagy field.

Health researchers' experiences, perceptions and barriers related to sharing study results with participants.

BACKGROUND: Although research participants are generally interested in receiving results from studies in which they participate, health researchers rarely communicate study findings to participants. The present study was designed to provide opportunity for a broad group of health researchers to describe their experiences and concerns related to sharing results (i.e. aggregate study findings) with research participants. METHODS: We used a mixed-methods concurrent triangulation design, relying on an online survey to capture health researchers' experiences, perceptions and barriers related to sharing study results with participants. Respondents were health researchers who conduct research that includes the consent of human subjects and hold a current appointment at an accredited academic medical institution within the United States. For quantitative data, the analytic strategy focused on item-level descriptive analyses. For the qualitative data, analyses focused on a priori themes and emergent subthemes. RESULTS: Respondents were 414 researchers from 44 academic medical institutions; 64.5% reported that results should always be shared with participants, yet 60.8% of respondents could identify studies in which they had a leadership role where results were not shared. Emergent subthemes from researchers' reasons why results should be shared included participant ownership of findings and benefits of results sharing to science. Reasons for not sharing included concerns related to participants' health literacy and participants' lack of desire for results. Across all respondents who described barriers to results sharing, the majority described logistical barriers. CONCLUSIONS: Study findings contribute to the literature by documenting researchers' perspectives and experiences about sharing results with research participants, which can inform efforts to improve results sharing. Most respondents indicated that health research results should always be shared with participants, although the extent to which many respondents described barriers to results sharing as well as reported reasons not to share results suggests difficulties with a one-size-fits-all approach to improving results sharing.

Efficacy of equine-assisted psychotherapy in veterans with posttraumatic stress disorder.

BACKGROUND: Posttraumatic stress disorder (PTSD) is a common and debilitating disorder among war veterans. Although complementary and alternative therapies are gaining acceptance in the treatment of PTSD, the efficacy of animal-based therapies in this disorder is unknown. The goal of equine-assisted psychotherapy (EAP) is to improve the social, emotional, and/or cognitive functions of individuals with PTSD. OBJECTIVE: This study aims to explore the effects of EAP on PTSD symptoms. We hypothesized that veterans with PTSD who participate in a standardized EAP program for 1 h per week for 6 weeks would experience decreased PTSD symptoms and would demonstrate increased resilience as compared with individuals who do not receive EAP intervention. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: We conducted a sequentially assigned, two-arm parallel group trial comparing 6 weeks of EAP with standard, previously established, ongoing PTSD therapy. Therapy was conducted at a community EAP facility in conjunction with an academic University Hospital. Twenty adult veterans with symptomatic PTSD completed the study. Ten adult veterans with previously diagnosed PTSD were assigned to EAP and received directed interaction with trained horses for one hour a week in groups of 3 or 4 individuals, while also continuing their previously established therapies. A certified therapist supervised the sessions, and a professional horse handler was also present. Results were compared with those from 10 adult veterans who only received their standard previously established PTSD care as prescribed by their provider. MAIN OUTCOME MEASURES: Changes in salivary cortisol, scores for the PTSD Check List-Military Version (PCL-M) and the Connor-Davidson Resilience Scale (CD-RISC) after 6 weeks of study were measured. RESULTS: Of the 20 enrolled patients, 10 served in Afghanistan, 5 served in Iraq, and 3 served in Vietnam. Subjects were (47 ±â€¯14) years old, were predominantly male, and had a body mass index of (29 ±â€¯7) kg/m2. They had (9.2 ±â€¯6.1) years of military service and carried 66% ±â€¯37% service-connected disability. PCL-M scores declined significantly in both groups and CD-RISC scores increased significantly in the EAP group. There was no difference between the groups with respect to the magnitude of change. CONCLUSION: As compared to the control group, a 6-week EAP program did not produce a statistically significant difference with respect to PCL-M and CD-RISC scores, or salivary cortisol. However, our results suggest that EAP may work as well as standard therapy with respect to these parameters. This study supports further inquiry into EAP as a potentially efficacious alternative for veterans suffering from PTSD. TRIAL REGISTRATION: ClinicalTrials.gov NCT #03039361.

A Perplexing Case of Pituitary Apoplexy Masquerading as Recurrent Meningitis.

In this article, we present an exceptional case of pituitary apoplexy in which a patient presented with meningeal symptoms of headache, stiff neck, and nausea rather than the classical findings of ophthalmoplegia and/or vision loss. The patient has had 2 similar presentations with cerebrospinal fluid showing neutrophilic pleocytosis, as well as a computed tomography scan showing a prominent pituitary gland. On current presentation, the patient's vital signs were stable and the physical examination was remarkable for nuchal rigidity. Magnetic resonance imaging of the head revealed an expansile pituitary gland lesion measuring 2.0 × 1.7 × 1.5 cm with upward displacement of the overlying optic chiasm. Cerebrospinal fluid showed neutrophilic pleocytosis, low glucose, high protein content, and negative bacterial and fungal cultures. Surgical decompression subsequently revealed findings consistent with pituitary apoplexy. This is the first known case in which a patient had recurrent episodes of meningitis due to pituitary apoplexy in the absence of a clinical deterioration. Early identification of apoplexy masquerading as meningitis will allow early surgical intervention, if necessary, to prevent complications, recurrence, and morbidity. As such, the presence of sterile meningitis in patients with a known pituitary adenoma should be considered for prompt surgical evaluation.

Adipose mTORC1 Suppresses Prostaglandin Signaling and Beige Adipogenesis via the CRTC2-COX-2 Pathway.

Beige adipocytes are present in white adipose tissue (WAT) and have thermogenic capacity to orchestrate substantial energy metabolism and counteract obesity. However, adipocyte-derived signals that act on progenitor cells to control beige adipogenesis remain poorly defined. Here, we show that adipose-specific depletion of Raptor, a key component of mTORC1, promoted beige adipogenesis through prostaglandins (PGs) synthesized by cyclooxygenase-2 (COX-2). Moreover, Raptor-deficient mice were resistant to diet-induced obesity and COX-2 downregulation. Mechanistically, mTORC1 suppressed COX-2 by phosphorylation of CREB-regulated transcription coactivator 2 (CRTC2) and subsequent dissociation of CREB to cox-2 promoter in adipocytes. PG treatment stimulated PKA and promoted differentiation of progenitor cells to beige adipocytes in culture. Ultimately, we show that pharmacological inhibition or suppression of COX-2 attenuated mTORC1 inhibition-induced thermogenic gene expression in inguinal WAT in vivo and in vitro. Our study identifies adipocyte-derived PGs as key regulators of white adipocyte browning, which occurs through mTORC1 and CRTC2.

Collaboration and Outside-the-Box Thinking to Overcome Training-Related Challenges for Including Patient Stakeholders as Data Collectors in a Patient-Engaged Research Project.

Including patient stakeholders as active members of the research team is essential to a patient-engaged research design. To hire community-based research staff for a study comparing the effectiveness of diabetes self-management programs for Latinos, we had to provide phlebotomy training which was not allowed under the fiscal guidelines of our funders. By collaborating with partners at the Clinical and Translational Science Center, we were not only able to find a creative solution and provide phlebotomy training to our research staff but the process of creating the training also contributed to improved infrastructure for patient-engaged research at our institution.

Autophagy, Inflammation, and Metabolism (AIM) Center of Biomedical Research Excellence: supporting the next generation of autophagy researchers and fostering international collaborations.

Recently, NIH has funded a center for autophagy research named the Autophagy, Inflammation, and Metabolism (AIM) Center of Biomedical Research Excellence, located at the University of New Mexico Health Science Center (UNM HSC), with aspirations to promote autophagy research locally, nationally, and internationally. The center has 3 major missions: (i) to support junior faculty in their endeavors to develop investigations in this area and obtain independent funding; (ii) to develop and provide technological platforms to advance autophagy research with emphasis on cellular approaches for high quality reproducible research; and (iii) to foster international collaborations through the formation of an International Council of Affiliate Members and through hosting national and international workshops and symposia. Scientifically, the AIM center is focused on autophagy and its intersections with other processes, with emphasis on both fundamental discoveries and applied translational research.

Learning and memory performance following acute intranasal insulin administration in abstinent smokers.

The highest incidence of relapse to smoking occurs within the first 2 weeks of a cessation attempt. In addition to enhanced nicotine craving, this phase of smoking cessation is also marked by learning and memory dysfunction. Many smokers are not able to overcome these symptoms, and they relapse to smoking shortly after trying to quit. In two clinical studies, we evaluated intranasal insulin for efficacy in improving learning and memory function during nicotine withdrawal. Our first study was a crossover evaluation (N = 19) following 20 hr of smoking abstinence. Study 2 was a parallel design study (N = 50) following 16 hr of abstinence. Intranasal insulin (60 IU) dose was administered in both studies and cognitive function was measured using California Verbal Learning Test-II. Intranasal insulin did not improve learning over the 5 verbal learning trials. In addition, intranasal insulin did not improve either short- or long-delay recall in either study. In summary, the one-time administration of intranasal insulin does not improve verbal learning and memory in smokers. Whether longer administration schedules may be of benefit should be evaluated in future studies.

What is the Role of Race and Ethnicity in the Development Of Thionamide-Induced Neutropenia?

Thionamides are anti-thyroid drugs (ATD) used to treat autonomous thyrotoxicosis. Although efficacious, these medications carry a risk of neutropenia or agranulocytosis. Some risk factors for ATD-induced neutropenia have been identified, including dose, age, and female sex, but the role of race and ethnicity has not been well studied. We hypothesize that there will be no effect of race or ethnicity on the change in Absolute Neutrophil Count (ANC) following initiation of ATD therapy. Data from the Electronic Medical Record at UNM HSC were obtained using a standard database query. Inclusion criteria were the prescription of an ATD, an ANC recorded within 30 days of initiating ATD therapy (Pre-ATD), and an ANC recorded 75 - 365 days after starting an ANC (Post-ATD). Patients taking other agents known to cause neutropenia were excluded. Racial and ethnic groups were assigned as follows: Hispanic, Non-Hispanic White, Native American, Black/African American, and Asian/Pacific Islander. Post-ATD ANC was defined as the nadir ANC after ATD initiation. "Delta ANC" was defined as ((Post-ATD ANC) - (Pre-ATD ANC)). ANOVA analysis with Bonferroni-adjusted post-hoc testing and multiple regression were performed to examine differences in the mean changes in ANC across ethnic groups. One hundred and twenty-three adult patients met inclusion and exclusion criteria and were included in the analysis. The Native American group showed a significantly greater Post-ATD ANC and Delta-ANC as compared to the other groups (p<0.001). In this cohort of New Mexicans with thyrotoxicosis, Native American race was protective against thionamide-induced neutropenia.