Putative cell-type-specific multiregional mode in posterior parietal cortex during coordinated visual behavior.

In the reach and saccade regions of the posterior parietal cortex (PPC), multiregional communication depends on the timing of neuronal activity with respect to beta-frequency (10-30 Hz) local field potential (LFP) activity, termed dual coherence. Neural coherence is believed to reflect neural excitability, whereby spiking tends to occur at a particular phase of LFP activity, but the mechanisms of multiregional dual coherence remain unknown. Here, we investigate dual coherence in the PPC of non-human primates performing eye-hand movements. We computationally model dual coherence in terms of multiregional neural excitability and show that one latent component, a multiregional mode, reflects shared excitability across distributed PPC populations. Analyzing the power in the multiregional mode with respect to different putative cell types reveals significant modulations with the spiking of putative pyramidal neurons and not inhibitory interneurons. These results suggest a specific role for pyramidal neurons in dual coherence supporting multiregional communication in PPC.

High prevalence of periodontitis in children and adolescents with type 2 diabetes.

BACKGROUND: The aim of the present study was to determine the prevalence of periodontitis in children and adolescents with type 2 diabetes, and if poor glycemic control is associated with increasing prevalence of the disease. METHODS: This is a cross-sectional study involving children and adolescents with type 2 diabetes. A questionnaire related to oral health care history and oral health behaviors was administered to each participant and they then underwent a full-mouth oral evaluation. In addition, clinical and metabolic parameters were extracted from the clinical chart. RESULTS: One hundred and twenty one children and adolescents (8-17 years, 11 months) participated. Overall, 45.5% presented some degree of periodontitis, with 10 (8.3%) mild, 36 (29.8%) moderate, and nine (7.4%) severe. The periodontitis group (PD-group) had higher mean gingival and plaque indexes, periodontal probing depth, and clinical attachment loss than the group without periodontitis (NoPD-group) (p<0.05). A statistically significant relationship between the prevalence of periodontitis and glycosylated hemoglobin (HbA1c) was verified in the bivariate (odds ratio [OR] 1.31 [95% CI, 1.13-1.53], p = 0.001) and multivariate (OR, 1.29 [95% CI, 1.03-1.61], p = 0.03) analysis. For the adjustment variables, associations were verified for duration of diabetes, age, body mass index z-score, lack of running water, insulin use, and acanthosis nigricans. CONCLUSIONS: Children and adolescents with type 2 diabetes presented high rates of periodontitis comparable with that seen in previous studies in youth with diabetes. Uncontrolled HbA1c influences prevalence of periodontal disease. The lack of matched control group and radiographs are limitations of the study. Comprehensive periodontal examination is essential for children and adolescents with type 2 diabetes to prevent, identify, and treat periodontitis early.

Excitatory/Inhibitory Responses Shape Coherent Neuronal Dynamics Driven by Optogenetic Stimulation in the Primate Brain.

Coherent neuronal dynamics play an important role in complex cognitive functions. Optogenetic stimulation promises to provide new ways to test the functional significance of coherent neural activity. However, the mechanisms by which optogenetic stimulation drives coherent dynamics remain unclear, especially in the nonhuman primate brain. Here, we perform computational modeling and experiments to study the mechanisms of optogenetic-stimulation-driven coherent neuronal dynamics in three male nonhuman primates. Neural responses arise from stimulation-evoked, temporally dynamic excitatory (E) and inhibitory (I) activity. Spiking activity is more likely to occur during E/I imbalances. Thus the relative difference in the driven E and I responses precisely controls spike timing by forming a brief time interval of increased spiking likelihood. Experimental results agree with parameter-dependent predictions from the computational models. These results demonstrate that optogenetic stimulation driven coherent neuronal dynamics are governed by the temporal properties of E/I activity. Transient imbalances in excitatory and inhibitory activity may provide a general mechanism for generating coherent neuronal dynamics without the need for an oscillatory generator.SIGNIFICANCE STATEMENT We examine how coherent neuronal dynamics arise from optogenetic stimulation in the primate brain. Using computational models and experiments, we demonstrate that coherent spiking and local field potential activity is generated by stimulation-evoked responses of excitatory and inhibitory activity in networks, extending the growing literature on neuronal dynamics. These responses create brief time intervals of increased spiking tendency and are consistent with previous observations in the literature that balanced excitation and inhibition controls spike timing, suggesting that optogenetic-stimulation-driven coherence may arise from intrinsic E/I balance. Most importantly, our results are obtained in nonhuman primates and thus will play a leading role in driving the use of causal manipulations with optogenetic tools to study higher cognitive functions in the primate brain.

FDA Regulation of Neurological and Physical Medicine Devices: Access to Safe and Effective Neurotechnologies for All Americans.

The United States Food and Drug Administration (FDA) ensures that patients in the U.S. have access to safe and effective medical devices. The Division of Neurological and Physical Medicine Devices reviews medical technologies that interface with the nervous system. This article addresses how to navigate the FDA's regulatory landscape to successfully bring medical devices to patients.

Breastfeeding Initiation Associated With Reduced Incidence of Diabetes in Mothers and Offspring.

OBJECTIVE: To examine associations between breastfeeding initiation and subsequent diabetes among First Nations (indigenous people in Canada who are not Métis or Inuit) and non-First Nations mothers and their offspring with and without gestational diabetes mellitus (GDM). METHODS: This retrospective database study included 334,553 deliveries (1987-2011) in Manitoba with up to 24 years of follow-up for diabetes using population-based databases. Information of breastfeeding initiation before hospital discharge was obtained from hospital abstracts recorded by nurses in postpartum wards. Cox proportional hazard models were applied to examine the association between breastfeeding initiation and risk of diabetes in mothers and their offspring. RESULTS: Breastfeeding initiation was recorded in 83% of non-First Nations mothers and 56% of First Nations mothers (P<.001). Breastfeeding initiation was associated with a reduced risk of incident (later developed) diabetes in non-First Nations mothers without GDM (hazard ratio [HR] 0.73 [or -27% of risk], 95% confidence interval [CI] 0.68-0.79), non-First Nations mothers with GDM (HR 0.78 or -22% of risk, CI 0.69-0.89), First Nations mothers without GDM (HR 0.89 or -11% of risk, CI 0.81-0.98), and First Nations mothers with GDM (HR 0.82 or -18% of risk, CI 0.73-0.92) with 24 years of follow-up or less. With 24 years of follow-up or less, breastfeeding initiation was associated with a 17% lower risk of youth-onset type 2 diabetes in offspring (HR 0.83, CI 0.69-0.99, P=.038). The association between breastfeeding initiation and subsequent diabetes in mothers and offspring was independent of family income, rural residence, First Nations status, GDM, parity, gestational hypertension, and age of the mother. CONCLUSION: Breastfeeding initiation is associated with a reduced risk of diabetes among women and their offspring in Manitoba. The results suggest that breastfeeding might be a potentially modifiable factor to reduce the risk of diabetes in both First Nations and non-First Nations women and children.

Exposure to Gestational Diabetes Mellitus: Impact on the Development of Early-Onset Type 2 Diabetes in Canadian First Nations and Non-First Nations Offspring.

OBJECTIVE: Type 2 diabetes is increasing in children worldwide, with Canadian First Nations (FN) children disproportionally affected. The prevalence of gestational diabetes mellitus (GDM) also is increasing. The objective of this study was to evaluate the impact of GDM exposure in utero and FN status on the subsequent risk of type 2 diabetes in offspring in the first 30 years of life. RESEARCH DESIGN AND METHODS: In this population-based historical prospective cohort study, we used administrative databases linked to a clinical database to explore the independent association and interaction between GDM and FN status on the subsequent development of type 2 diabetes in offspring. RESULTS: Among 321,008 births with a median follow-up of 15.1 years, both maternal GDM and FN status were independently associated with subsequent risk of type 2 diabetes in offspring in the first 30 years of life (hazard ratio 3.03 [95% CI 2.44-3.76; P < 0.0001] vs. 4.86 [95% CI 4.08-5.79; P < 0.0001], respectively). No interaction between GDM and FN status on type 2 diabetes risk was observed. FN status had a stronger impact on the development of type 2 diabetes in offspring than GDM. CONCLUSIONS: GDM is an important modifiable risk factor for type 2 diabetes, and its prevention may reduce the prevalence of subsequent type 2 diabetes in offspring. This study adds unique and rigorous evidence to the global public health debate about the impact of GDM on the long-term health of offspring.

The Metabolic Phenotype of Youth Onset Type 2 Diabetes: The Role of Pregestational Diabetes Exposure and the Hepatic Nuclear Factor 1Alpha G319S Polymorphism.

INTRODUCTION: The influence of exposure to diabetes in utero and the HNF-1α G319S polymorphism on the metabolic phenotype of youth with T2DM at diagnosis is unknown. The objective of this study is to describe the metabolic phenotype at diagnosis of youth with T2DM: a) by exposure to gestational or pregestational diabetes and b) by HNF-1α G319S genotype. METHODS: A cross-sectional retrospective chart review of youth with T2DM diagnosed between 2006 and 2011 seen at a single centre was performed. The primary variables of interest and selected clinical and biochemical characteristics at birth and at diagnosis of diabetes were extracted. Descriptive statistics and regression analyses were undertaken. RESULTS: One hundred eighty-four youth were included. Youth exposed to pregestational diabetes were younger at diagnosis (-1.26 years, p<0.001), had a shorter gestation (-1.73 weeks, p<0.001) and a lower waist z-score (-2.77, p<0.001) compared to those not exposed to diabetes in utero. Youth homozygous for the HNF-1α G319S polymorphism were younger (-1.77 years p<0.001), had a lower BMI z-score (-0.32, p=0.04), waist z-score (-1.91, p=0.04), HbA1c (-1.73%; 18.9 mmol/mol, p<0.01), triglycerides (-90.3 mg/dl; -1.02 mmol/L, p=0.04) and higher HDL-c (8.88 mg/dl; 0.23 mmol/L, p=0.001) compared to wild-type youth at diagnosis. Homozygote youth were less likely to have hypertension or acanthosis nigricans at diagnosis (OR 0.27, p=0.03; OR 0.32, p=0.04 respectively). CONCLUSION: Differences in the metabolic phenotype of subgroups of youth with T2DM suggest differences in the pathophysiology of diabetes. An understanding of specific phenotypes is necessary to plan and inform both prevention and intervention strategies.

Persistent Albuminuria in Children with Type 2 Diabetes: A Canadian Paediatric Surveillance Program Study.

OBJECTIVE: To determine the prevalence and the clinical features associated with persistent albuminuria in Canadian children aged <18 years with type 2 diabetes. STUDY DESIGN: This national prospective surveillance study involved a network of pediatricians and pediatric endocrinologists. Cases of persistent albuminuria in children with type 2 diabetes were reported during a 24-month period from 2010 to 2012. Persistent albuminuria was defined as an elevated albumin-to-creatinine ratio in a minimum of 2 out of 3 urine samples obtained at least 1 month apart over 3-6 months and confirmed with a first morning sample. Descriptive statistics were used to illustrate demographic and clinical features of the population. The prevalence of persistent albumuria was estimated using data from a previous national surveillence study of type 2 diabetes in children. RESULTS: Fifty cases were reported over the 24-month study period. The estimated prevalence of persistent albuminuria in children with type 2 diabetes in Canada was 5.1%. The median duration of diabetes at the time of diagnosis of albuminuria was 21 days (IQR, 0-241 days). Almost two-thirds (64%) were female, 80% were of Canadian First Nations heritage, and 76% were from Manitoba. Exposure to gestational or pregestational diabetes in utero occurred in 65%, and 48% had a family history of diabetes-related renal disease. Structural anomalies of the kidney were found in 37%. CONCLUSION: Persistent albuminuria occurs in youths with type 2 diabetes in the first year after diagnosis, demonstrates regional variation, and is associated with First Nations heritage and exposure to maternal diabetes during pregnancy.

Beating Diabetes Together: A Mixed-Methods Analysis of a Feasibility Study of Intensive Lifestyle Intervention for Youth with Type 2 Diabetes.

OBJECTIVES: The purpose of this study was to assess the feasibility and lived experiences of an intensive group-based lifestyle intervention for youth with type 2 diabetes (Beating Diabetes Together) (BDT). METHODS: The study included 12 Indigenous youth with type 2 diabetes (mean age, 14 years; n=9 girls); they participated in a 16-week pilot study of an intensive, group-based lifestyle intervention. We conducted a mixed-methods investigation of the cardiometabolic responses and lived experiences in the intervention. Of the 12 youth with cardiometabolic risk data, 5 youth and 2 mothers participated in semistructured interviews. Interview participants were purposely selected based on the frequency of attendance and availability. RESULTS: The intervention was well attended (>75% retention), and youth perceived significant benefits from participation. Thematic analysis of the interviews revealed 3 major themes. First, youth and parents described living with type 2 diabetes as being emotionally challenging. They described this experience as being isolating and connected to feelings of guilt and defeat. Second, youth and parents discussed benefits of participating in BDT. They shared the significance of positive relationships and experiences and how those have helped to manage their illness. Third, youth described the aspects that they most enjoyed at BDT. Peer support was an important determinant of physical activity, but they considered dietary changes to be individual behaviours. Glycemic control, blood pressure and anthropometric measures were not different following the intervention. CONCLUSIONS: Our findings support the importance of maintaining an inclusive environment and relationship building when designing strategies to promote behaviour modification for Indigenous youth living with type 2 diabetes.

Children have type 2 diabetes too: an historical perspective.

Prior to 1985, type 2 diabetes was a disease of adults. Simultaneously with the global epidemic of childhood obesity, type 2 diabetes has increased in children. Initially, the presentation of small case series of type 2 diabetes in children was met with skepticism. As the number and size of the case series grew and the first long-term outcomes of end-stage complications in young adults appeared in the literature, the international community took notice with guarded interest. Type 2 diabetes disproportionately affects the children of specific ethnic groups and from disadvantaged socioeconomic environments, especially Indigenous populations. The past decade has seen unprecedented intense global interest in the etiology, treatment, and prevention of type 2 diabetes in children.

Maternal diabetes mellitus and congenital anomalies of the kidney and urinary tract (CAKUT) in the child.

BACKGROUND: Congenital anomalies of the kidney and urinary tract (CAKUT) are the primary cause of chronic kidney disease in children. The relevance of timing of diabetes mellitus (DM) exposure on risk of CAKUT in exposed children is unknown. STUDY DESIGN: Population-based nested case-control study. SETTING & PARTICIPANTS: Infants born between fiscal years 1996/1997 and 2009/2010 in Manitoba, Canada, identified using administrative data housed at the Manitoba Centre for Health Policy. PREDICTORS: Pregestational (including first 20 weeks' gestation) and gestational (>20 weeks) DM and relevant confounders (maternal age; renin-angiotensin-aldosterone system inhibitor use; low socioeconomic status; alcohol, illicit drug, and smoking use during pregnancy; region of residence; and size for gestational age [surrogate of glycemic control]). OUTCOME: CAKUT identified by International Classification of Diseases codes. RESULTS: 945 case patients with CAKUT and 4,725 controls (matched for gestational age, sex, and birth year) were identified. Maternal pregestational DM occurred in 39 (4.1%) of the CAKUT group and 111 (2.3%) controls (P = 0.002), whereas gestational DM occurred in 40 (4.2%) of the CAKUT group and 157 (3.3%) controls (P = 0.2). In the conditional multivariable logistic regression model, pregestational DM was associated with CAKUT (OR, 1.67; 95% CI, 1.14-2.46), whereas gestational DM was not (OR, 1.29; 95% CI, 0.90-1.85). Both large (LGA) and small for gestational age (SGA) also were associated significantly with CAKUT (LGA: OR, 1.34 [95% CI, 1.11-1.63]; SGA: OR, 1.59 [95% CI, 1.26-2.01]). LIMITATIONS: Lack of data for maternal glycemic control and body mass index. CONCLUSIONS: This study suggests that DM in the first 20 weeks of pregnancy is associated with CAKUT in exposed infants. The association between CAKUT and LGA suggests that poor glycemic control increases risk. Screening and intervention studies in women of childbearing age with DM are warranted to determine whether the risk of chronic kidney disease in children can be modified.

Interprofessional education using simulation of an overnight inpatient ward shift.

In healthcare it is rare for professionals to practice together before they practice together. Nightmare Night Care is an annual interprofessional voluntary event for health sciences students in nursing, medicine and pharmacy to come together for a simulated hospital overnight ward shift. The purpose of this study was to investigate the interprofessional knowledge, skills and attitudes the students learn from this experience. Students responded to surveys before (n = 45) and after the event (n = 11) regarding their understanding of the goals of interprofessional education (IPE), roles and responsibilities of other professions, and what they learned from this event. Responses demonstrated that students are eager to learn in interprofessional settings and that IPE events may aid in building understanding and communication between professions. IPE events are an opportunity to allow students to learn about each other; however, they must occur frequently, and must include an orientation on role clarification if they are to have an effect on changing preconceived stereotypes of the other professions.

The Improving Renal Complications in Adolescents With Type 2 Diabetes Through the REsearch (iCARE) Cohort Study: rationale and Protocol.

BACKGROUND: Youth-onset type 2 diabetes is associated with a high burden of renal complications, culminating with end stage kidney disease in early adulthood. The establishment of relevant bioclinical determinants of albuminuria and ultimately progression of chronic kidney disease in youth is critically important to facilitate patient risk stratification and aid in the development of treatment targets and tailored prevention strategies. In response to the important gaps in knowledge, we created a prospective cohort study of youth with type 2 diabetes titled the Improving Renal Complications in Adolescents with Type 2 Diabetes through the REsearch (iCARE) Study. METHODS: iCARE is a prospective observational cohort study of individuals with type 2 diabetes diagnosed prior to 18 years of age; the recruitment target was 400 patients. Phase 1 entailed a detailed phenotypic assessment of youth, including anthropometrics, biochemistry, 24-hour ambulatory blood pressure monitoring, overnight urine collections for albumin excretion, renal ultrasound and iohexol-derived glomerular filtration rate. Phase 2 of the study is an evaluation of psychological factors, including hair-derived cortisol; validated questionnaires for perceived stress, distress and resiliency; and a detailed evaluation of systemic and urine inflammatory biomarkers. Annual follow up is planned to assess temporal associations between clinical risk factors and renal outcomes, including progression of albuminuria. CONCLUSION: This study will provide novel insight into the risk factors for albuminuria and progression of chronic kidney disease in youth with type 2 diabetes. New knowledge generated by this study will inform clinical care, and the infrastructure developed will provide a framework for future intervention studies.

Effects of lifestyle intervention on dietary intake, physical activity level, and gestational weight gain in pregnant women with different pre-pregnancy Body Mass Index in a randomized control trial.

BACKGROUND: The objectives of this study were to assess the efficacy of lifestyle intervention on gestational weight gain in pregnant women with normal and above normal body mass index (BMI) in a randomized controlled trial. METHODS: A total of 116 pregnant women (<20 weeks of pregnancy) without diabetes were enrolled and 113 pregnant women completed the program. Participants were randomized into intervention and control groups. Women in the intervention group received weekly trainer-led group exercise sessions, instructed home exercise for 3-5-times/week during 20-36 weeks of gestation, and dietary counseling twice during pregnancy. Participants in the control group did not receive the intervention. All participants completed a physical activity questionnaire and a 3-day food record at enrolment and 2 months after enrolment. RESULTS: The participants in the intervention group with normal pre-pregnancy BMI (≤24.9 kg/M2, n = 30) had lower gestational weight gain (GWG), offspring birth weight and excessive gestational weight gain (EGWG) on pregnancy weight gain compared to the control group (n = 27, p < 0.05). Those weight related-changes were not detected between the intervention (n = 27) and control group (n = 29) in the above normal pre-pregnancy BMI participants. Intervention reduced total calorie, total fat, saturated fat and cholesterol intake were detected in women with normal or above normal pre-pregnancy BMI compared to the control group (p < 0.05 or 0.01). Increased physical activity and reduced carbohydrate intake were detected in women with normal (p < 0.05), but not above normal, pre-pregnancy BMI at 2 months after the onset of the intervention compared to the control group. CONCLUSION: The results of the present study demonstrated that the lifestyle intervention program decreased EGWG, GWG, offspring birth weight in pregnant women with normal, but not above normal, pre-pregnancy BMI, which was associated with increased physical activity and decreased carbohydrate intake. TRIAL REGISTRATION: NCT00486629.

Elements and enablers for interprofessional education clinical placements in diabetes teams.

OBJECTIVE: The purpose of this review is to describe the elements and enablers for interprofessional education (IPE) clinical placements in diabetes teams. METHODS: We describe the development of an IPE clinical placement for health professional students in a diabetes team and share the lessons learned over 6 years, from 2008 to 2013. The 6 collaborative practice competencies of the Canadian Interprofessional Health Collaborative and the requirements for Accreditation of Interprofessional Health Professional Education opportunities guided the development of an IPE clinical placement in a diabetes team. RESULTS: A formal IPE clinical placement in diabetes teams requires attention to the site and diabetes team-specific elements and enablers for IPE. That includes students and preceptors from 2 or more health professions, a formal curriculum on collaborative care, adequate IPE resources and strong institutional support for a culture of collaborative care and integration of students in diabetes teams. CONCLUSIONS: Diabetes teams can provide a valuable IPE opportunity for health professional students, recognizing that there are challenges that must be addressed in organizational structure of clinical placements in diabetes teams. Studies of the effectiveness of IPE in diabetes teams on collaboration competencies in future diabetes healthcare professionals and long-term patient outcomes are needed.