Investigation of the Effect of Peptide p5 Targeting CDK5-p25 Hyperactivity on Munc18-1 (P67) Regulating Neuronal Exocytosis Using Molecular Simulations.

Munc18-1 is an SM (sec1/munc-like) family protein involved in vesicle fusion and neuronal exocytosis. Munc18-1 is known to regulate the exocytosis process by binding with closed- and open-state conformations of Syntaxin1, a protein belonging to the SNARE family established to be central to the exocytosis process. Our previous work studied peptide p5 as a promising drug candidate for CDK5-p25 complex, an Alzheimer's disease (AD) pathological target. Experimental in vivo and in vitro studies suggest that Munc18-1 promotes p5 to selectively inhibit the CDK5-p25 complex without affecting the endogenous CDK5 activity, a characteristic of remarkable therapeutic implications. In this paper, we identify several binding modes of p5 with Munc18-1 that could potentially affect the Munc18-1 binding with SNARE proteins and lead to off-target effects on neuronal communication using molecular dynamics simulations. Recent studies indicate that disruption of Munc18-1 function not only disrupts neurotransmitter release but also results in neurodegeneration, exhibiting clinical resemblance to other neurodegenerative conditions such as AD, causing diagnostic and treatment challenges. We characterize such interactions between p5 and Munc18-1, define the corresponding pharmacophores, and provide guidance for the in vitro validation of our findings to improve therapeutic efficacy and safety of p5.

Affective disorders, weight change, and patient engagement in a rural behavioral weight loss trial.

BACKGROUND: Adults in rural areas have a higher prevalence of obesity and some mental health conditions. The degree to which mental health influences weight loss among rural residents remains unclear. This study evaluated changes in body weight, physical activity, diet, and program engagement outcomes in a cohort of participants with vs. without an affective disorder in a behavioral weight loss trial. METHODS: A sample of 1407 adults with obesity were recruited from rural U.S. primary care practices to participate in a weight loss trial. In this secondary analysis, participants were stratified by those with vs. without an affective disorder at baseline. Mixed models were used to estimate changes in outcomes over 24 months. RESULTS: One-third of participants (n = 468) had an affective disorder. After covariate adjustment, both groups experienced significant weight loss over 24 months, but weight loss was significantly less among those with an affective disorder at all follow-up times (all p's < 0.001; 24-month weight loss -2.7 ±â€¯0.4 vs. -4.8 ±â€¯0.3 kg). Compared to those without an affective disorder, participants with an affective disorder also had significantly less improvement in physical activity and fruit/vegetable consumption, lower attendance at weight loss sessions, and less engagement in setting weight loss goals and strategies. CONCLUSION: Participants with an affective disorder lost less body weight and less improvement in lifestyle measures over 24 months. These trends paralleled reduced engagement in critical intervention activities such as weight loss session attendance. Future interventions should consider additional methods to minimize disengagement in adults with underlying affective disorders.

Effect of Behavioral Therapy With In-Clinic or Telephone Group Visits vs In-Clinic Individual Visits on Weight Loss Among Patients With Obesity in Rural Clinical Practice: A Randomized Clinical Trial.

Importance: Rural populations have a higher prevalence of obesity and poor access to weight loss programs. Effective models for treating obesity in rural clinical practice are needed. Objective: To compare the Medicare Intensive Behavioral Therapy for Obesity fee-for-service model with 2 alternatives: in-clinic group visits based on a patient-centered medical home model and telephone-based group visits based on a disease management model. Design, Setting, and Participants: Cluster randomized trial conducted in 36 primary care practices in the rural Midwestern US. Inclusion criteria included age 20 to 75 years and body mass index of 30 to 45. Participants were enrolled from February 2016 to October 2017. Final follow-up occurred in December 2019. Interventions: All participants received a lifestyle intervention focused on diet, physical activity, and behavior change strategies. In the fee-for-service intervention (n = 473), practice-employed clinicians provided 15-minute in-clinic individual visits at a frequency similar to that reimbursed by Medicare (weekly for 1 month, biweekly for 5 months, and monthly thereafter). In the in-clinic group intervention (n = 468), practice-employed clinicians delivered group visits that were weekly for 3 months, biweekly for 3 months, and monthly thereafter. In the telephone group intervention (n = 466), patients received the same intervention as the in-clinic group intervention, but sessions were delivered remotely via conference calls by centralized staff. Main Outcomes and Measures: The primary outcome was weight change at 24 months. A minimum clinically important difference was defined as 2.75 kg. Results: Among 1407 participants (mean age, 54.7 [SD, 11.8] years; baseline body mass index, 36.7 [SD, 4.0]; 1081 [77%] women), 1220 (87%) completed the trial. Mean weight loss at 24 months was -4.4 kg (95% CI, -5.5 to -3.4 kg) in the in-clinic group intervention, -3.9 kg (95% CI, -5.0 to -2.9 kg) in the telephone group intervention, and -2.6 kg (95% CI, -3.6 to -1.5 kg) in the in-clinic individual intervention. Compared with the in-clinic individual intervention, the mean difference in weight change was -1.9 kg (97.5% CI, -3.5 to -0.2 kg; P = .01) for the in-clinic group intervention and -1.4 kg (97.5% CI, -3.0 to 0.3 kg; P = .06) for the telephone group intervention. Conclusions and Relevance: Among patients with obesity in rural primary care clinics, in-clinic group visits but not telephone-based group visits, compared with in-clinic individual visits, resulted in statistically significantly greater weight loss at 24 months. However, the differences were small in magnitude and of uncertain clinical importance. Trial Registration: ClinicalTrials.gov Identifier: NCT02456636.

"Knee-To-Knee" Position for Minor Procedures in Infants and Toddlers- Dentists Attitudes.

OBJECTIVE: The objective of this survey was to assess attitudes of pediatric dentists in Israel toward using "knee-to-knee" positioning for dental examinations and for minor procedures in infants and toddlers. STUDY DESIGN: An anonymous questionnaire was distributed among specialists in pediatric dentistry. Eleven questions accessed demographic data, professional experience and attitudes toward the use of the "knee-to-knee" position. RESULTS: Of 68 respondents, 66 (97%) reported using "knee-to-knee" positioning for dental checkups. In addition, 52 (76%) reported performing other procedures in the "knee-to-knee" position. Fluoride application and oral hygiene instructions are the most common procedures performed in the "knee-to-knee" position. CONCLUSIONS: "Knee-to-knee" positioning was found very convenient for dental examinations and other simple procedures in very young children.

Hypoglycaemia represents a clinically significant manifestation of PIK3CA- and CCND2-associated segmental overgrowth.

The PI3K-AKT signalling cascade has a highly conserved role in a variety of processes including cell growth and glucose homoeostasis. Variants affecting this pathway can lead to one of several segmental overgrowth disorders. These conditions are genetically heterogeneous and require tailored, multidisciplinary involvement throughout life. Hypoglycaemia is common in other overgrowth syndromes but has been described only sporadically in association with PIK3CA and CCND2 variants. We report a cohort of 6 children with megalencephaly-capillary malformation (MCAP) and megalencephaly-polydactyly-polymicrogyria-hydrocephalus (MPPH) syndromes who developed clinically significant hypoglycaemia. Based on our findings, we suggest that segmental overgrowth patients should be screened for low blood glucose levels during childhood and there should be early specialist endocrine review in any children who develop hypoglycaemia.

The Role of HIPAA Omnibus Rules in Reducing the Frequency of Medical Data Breaches: Insights From an Empirical Study.

Policy Points: Frequent data breaches in the US health care system undermine the privacy of millions of patients every year-a large number of which happen among business associates of the health care providers that continue to gain unprecedented access to patients' data as the US health care system becomes digitally integrated. Implementation of the HIPAA Omnibus Rules in 2013 has led to a significant decrease in the number of privacy breach incidents among business associates. CONTEXT: Frequent data breaches in the US health care system undermine the privacy of millions of patients every year. A large number of such breaches happens among business associates of the health care providers that continue to gain unprecedented access to patients' data as the US health care system becomes digitally integrated. The Omnibus Rules of the Health Insurance Portability and Accountability Act (HIPAA), which were enacted in 2013, significantly increased the regulatory oversight and privacy protection requirements of business associates. The objective of this study is to empirically examine the effects of this shift in policy on the frequency of medical privacy breaches among business associates in the US health care system. The findings of this research shed light on how regulatory efforts can protect patients' privacy. METHODS: Using publicly available data on breach incidents between October 2009 and August 2017 as reported by the Office for Civil Rights (OCR), we conducted an interrupted time-series analysis and a difference-in-differences analysis to examine the immediate and long-term effects of implementation of HIPAA omnibus rules on the frequency of medical privacy breaches. FINDINGS: We show that implementation of the omnibus rules led to a significant reduction in the number of breaches among business associates and prevented 180 privacy breaches from happening, which could have affected nearly 18 million Americans. CONCLUSIONS: Implementation of HIPAA omnibus rules may have been a successful federal policy in enhancing privacy protection efforts and reducing the number of breach incidents in the US health care system.

Modeling, validation and verification of three-dimensional cell-scaffold contacts from terabyte-sized images.

BACKGROUND: Cell-scaffold contact measurements are derived from pairs of co-registered volumetric fluorescent confocal laser scanning microscopy (CLSM) images (z-stacks) of stained cells and three types of scaffolds (i.e., spun coat, large microfiber, and medium microfiber). Our analysis of the acquired terabyte-sized collection is motivated by the need to understand the nature of the shape dimensionality (1D vs 2D vs 3D) of cell-scaffold interactions relevant to tissue engineers that grow cells on biomaterial scaffolds. RESULTS: We designed five statistical and three geometrical contact models, and then down-selected them to one from each category using a validation approach based on physically orthogonal measurements to CLSM. The two selected models were applied to 414 z-stacks with three scaffold types and all contact results were visually verified. A planar geometrical model for the spun coat scaffold type was validated from atomic force microscopy images by computing surface roughness of 52.35 nm ±31.76 nm which was 2 to 8 times smaller than the CLSM resolution. A cylindrical model for fiber scaffolds was validated from multi-view 2D scanning electron microscopy (SEM) images. The fiber scaffold segmentation error was assessed by comparing fiber diameters from SEM and CLSM to be between 0.46% to 3.8% of the SEM reference values. For contact verification, we constructed a web-based visual verification system with 414 pairs of images with cells and their segmentation results, and with 4968 movies with animated cell, scaffold, and contact overlays. Based on visual verification by three experts, we report the accuracy of cell segmentation to be 96.4% with 94.3% precision, and the accuracy of cell-scaffold contact for a statistical model to be 62.6% with 76.7% precision and for a geometrical model to be 93.5% with 87.6% precision. CONCLUSIONS: The novelty of our approach lies in (1) representing cell-scaffold contact sites with statistical intensity and geometrical shape models, (2) designing a methodology for validating 3D geometrical contact models and (3) devising a mechanism for visual verification of hundreds of 3D measurements. The raw and processed data are publicly available from https://isg.nist.gov/deepzoomweb/data/ together with the web -based verification system.

Medication Adherence Does Not Explain Black-White Differences in Cardiometabolic Risk Factor Control among Insured Patients with Diabetes.

BACKGROUND: Among patients with diabetes, racial differences in cardiometabolic risk factor control are common. The extent to which differences in medication adherence contribute to such disparities is not known. We examined whether medication adherence, controlling for treatment intensification, could explain differences in risk factor control between black and white patients with diabetes. METHODS: We identified three cohorts of black and white patients treated with oral medications and who had poor risk factor control at baseline (2009): those with glycated hemoglobin (HbA1c) >8 % (n = 37,873), low-density lipoprotein cholesterol (LDL-C) >100 mg/dl (n = 27,954), and systolic blood pressure (SBP) >130 mm Hg (n = 63,641). Subjects included insured adults with diabetes who were receiving care in one of nine U.S. integrated health systems comprising the SUrveillance, PREvention, and ManagEment of Diabetes Mellitus (SUPREME-DM) consortium. Baseline and follow-up risk factor control, sociodemographic, and clinical characteristics were obtained from electronic health records. Pharmacy-dispensing data were used to estimate medication adherence (i.e., medication refill adherence [MRA]) and treatment intensification (i.e., dose increase or addition of new medication class) between baseline and follow-up. County-level income and educational attainment were estimated via geocoding. Logistic regression models were used to test the association between race and follow-up risk factor control. Models were specified with and without medication adherence to evaluate its role as a mediator. RESULTS: We observed poorer medication adherence among black patients than white patients (p < 0.01): 50.6 % of blacks versus 39.7 % of whites were not highly adherent (i.e., MRA <80 %) to HbA1c oral medication(s); 58.4 % of blacks and 46.7 % of whites were not highly adherent to lipid medication(s); and 33.4 % of blacks and 23.7 % of whites were not highly adherent to BP medication(s). Across all cardiometabolic risk factors, blacks were significantly less likely to achieve control (p < 0.01): 41.5 % of blacks and 45.8 % of whites achieved HbA1c <8 %; 52.6 % of blacks and 60.8 % of whites achieved LDL-C <100; and 45.7 % of blacks and 53.6 % of whites achieved SBP <130. Adjusting for medication adherence/treatment intensification did not alter these patterns or model fit statistics. CONCLUSIONS: Medication adherence failed to explain observed racial differences in the achievement of HbA1c, LDL-C, and SBP control among insured patients with diabetes.

Trends in diabetes incidence among 7 million insured adults, 2006-2011: the SUPREME-DM project.

An observational cohort analysis was conducted within the Surveillance, Prevention, and Management of Diabetes Mellitus (SUPREME-DM) DataLink, a consortium of 11 integrated health-care delivery systems with electronic health records in 10 US states. Among nearly 7 million adults aged 20 years or older, we estimated annual diabetes incidence per 1,000 persons overall and by age, sex, race/ethnicity, and body mass index. We identified 289,050 incident cases of diabetes. Age- and sex-adjusted population incidence was stable between 2006 and 2010, ranging from 10.3 per 1,000 adults (95% confidence interval (CI): 9.8, 10.7) to 11.3 per 1,000 adults (95% CI: 11.0, 11.7). Adjusted incidence was significantly higher in 2011 (11.5, 95% CI: 10.9, 12.0) than in the 2 years with the lowest incidence. A similar pattern was observed in most prespecified subgroups, but only the differences for persons who were not white were significant. In 2006, 56% of incident cases had a glycated hemoglobin (hemoglobin A1c) test as one of the pair of events identifying diabetes. By 2011, that number was 74%. In conclusion, overall diabetes incidence in this population did not significantly increase between 2006 and 2010, but increases in hemoglobin A1c testing may have contributed to rising diabetes incidence among nonwhites in 2011.

Incidence and factors associated with medication nonadherence in patients with mental illness: a cross-sectional study.

BACKGROUND: In spite of the progress made in the treatment of psychiatric disorders during the last few decades, nonadherence continues to be a frequent phenomenon, often associated with potentially severe clinical consequences and increased health-care costs. There are numerous factors associated with medication nonadherence in patients with mental illness. The aim of the study was to determine the incidence and factors associated with medication nonadherence among psychiatric outpatients. MATERIALS AND METHODS: A cross-sectional study was carried out in the outpatient psychiatric department of an Indian tertiary care private hospital over a period of 1 year. Patients aged 18 years and above who presented with mental illness as diagnosed by the International Classification of Diseases (ICD)-10 and who were receiving at least one psychotropic medication for at least 1 month were included in the study. Medication adherence was assessed using the Medication Adherence Rating Scale (MARS). RESULTS: Of the 400 patients, 172 (43%) were nonadherent to their prescribed medications. There is a statistically significant association between the education (P = 0.001), number of drugs (P = 0.002), family income (P = 0.013), and nonadherence. Among the 172 patients, 33.5 % were nonadherent to their therapy due to patient-related factors followed by drug-related factors (32%) and disease-related factors (31%). CONCLUSION: The overall incidence of medication nonadherence in patients with mental illness was 43%. Numerous factors contributed to medication nonadherence. Strategies need to be developed and implemented to enhance medication adherence, and thereby achieve a better therapeutic outcome in patients with mental illness.

The ACCURE-trial: the effect of appendectomy on the clinical course of ulcerative colitis, a randomised international multicenter trial (NTR2883) and the ACCURE-UK trial: a randomised external pilot trial (ISRCTN56523019).

BACKGROUND: Over the past 20 years evidence has accumulated confirming the immunomodulatory role of the appendix in ulcerative colitis (UC). This led to the idea that appendectomy might alter the clinical course of established UC. The objective of this body of research is to evaluate the short-term and medium-term efficacy of appendectomy to maintain remission in patients with UC, and to establish the acceptability and cost-effectiveness of the intervention compared to standard treatment. METHODS/DESIGN: These paired phase III multicenter prospective randomised studies will include patients over 18 years of age with an established diagnosis of ulcerative colitis and a disease relapse within 12 months prior to randomisation. Patients need to have been medically treated until complete clinical (Mayo score <3) and endoscopic (Mayo score 0 or 1) remission. Patients will then be randomised 1:1 to a control group (maintenance 5-ASA treatment, no appendectomy) or elective laparoscopic appendectomy plus maintenance treatment. The primary outcome measure is the one year cumulative UC relapse rate - defined both clinically and endoscopically as a total Mayo-score ≥5 with endoscopic subscore of 2 or 3. Secondary outcomes that will be assessed include the number of relapses per patient at 12 months, the time to first relapse, health related quality of life and treatment costs, and number of colectomies in each arm. DISCUSSION: The ACCURE and ACCURE-UK trials will provide evidence on the role and acceptability of appendectomy in the treatment of ulcerative colitis and the effects of appendectomy on the disease course. TRIAL REGISTRATION: NTR2883 ; ISRCTN56523019.

Levels of Stress among General Practitioners, Students and Specialists In Pediatric Dentistry during Dental Treatment.

OBJECTIVE: To assess self-reported stress during the performance of different procedures in pediatric dentistry, according to the professional experience of the dentists. STUDY DESIGN: During the years 2010 to 2011, an anonymous survey was administered by means of an internet link, and by distribution at professional meetings of dentists . RESULTS: No statistically significant differences in stress were reported for maxilla and mandibular procedures. Placement of a rubber dam was rated as the most stressful procedure among dental students. For general practitioners and specialists, injection of local anesthesia to an anxious child was the most stressful procedure, regardless of age, sex, or years of professional experience. A negative correlation was found between years of experience and level of stress for all the procedures surveyed, but not for the use of nitrous oxide. No differences were found between male and female dentists in stress scores for any of the procedures. CONCLUSION: Higher rates of stress during operative procedures were reported among dental students than among experienced dentists. Anxiety of the pediatric patients, but not the location of the procedure: maxillary or mandibular, affected the dentists' reported level of stress.

Intensification of antihyperglycemic therapy among patients with incident diabetes: a Surveillance Prevention and Management of Diabetes Mellitus (SUPREME-DM) study.

PURPOSE: Antihyperglycemic medication intensification practices among patients with incident diabetes are incompletely understood. We characterized the first intensification the year after oral antihyperglycemic medication initiation among incident diabetes patients. METHODS: This retrospective cohort study across 11 US health systems included adults identified with incident diabetes between 2005 and 2009 who started oral antihyperglycemic monotherapy or combination therapy within 6 months after diabetes identification. We determined intensification, defined as increased index medication dosage, addition of another oral medication, or switch to/addition of insulin 31-365 days after initial antihyperglycemic dispensing. Cox regression was used to assess intensification for patient, temporal, and system covariates, adjusting for glycosylated hemoglobin (HbA1c) as a time-dependent variable. RESULTS: Among 41,233 patients, 33.5% and 45.3% had treatment intensified within 6 and 12 months, respectively. This first intensification was most often with increased index medication dosage (78%), least often with insulin (<1%). HbA1c% was strongly associated with intensification (adjusted hazard ratios [HR] 1.59, 3.62, 4.44, and 5.52 for HbA1c 6.5% to <7%, 7% to <7.5%, 7.5 to <8%, and ≥8%, respectively, all P < 0.001, compared with HbA1c < 6.5%). In patients initially on monotherapy, age modified the HbA1c effect: at HbA1c < 7%, the HR differed little between middle-aged and older patients; at HbA1c ≥ 7%, the HR decreased with older age (e.g., age 40-49 years and HbA1c ≥ 8%: HR 8.14; age ≥ 80 years and HbA1c ≥ 8%: HR 4.44; compared with age ≥ 80 years and HbA1c < 6.5%). Within 1 year, 84.3% achieved HbA1c < 8%; 65.1% achieved HbA1c < 7%. CONCLUSIONS: Clinicians appear to be applying treatment intensification guidelines and individualizing therapy by considering patient age, achieving glycemic control among most incident diabetes patients.

Development and validation of a real time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) assay for investigation of wild poliovirus type 1-South Asian (SOAS) strain reintroduced into Israel, 2013 to 2014.

In February 2013, wild poliovirus type 1 (WPV1) was reintroduced into southern Israel and resulted in continuous silent circulation in the highly immune population. As a part of the public health emergency response, a novel real time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) assay was developed, to allow for the sensitive and specific detection of the circulatingWPV1-South Asian (SOAS) strain. Specific primers and probes derived from the VP-1 region were designed, based on sequenced sewage isolates, and used to simultaneously amplify this WPV1-SOAS sequence together with bacteriophage MS-2 as internal control. High titre WPV1-SOAS stock virus was used for assay optimisation and 50 processed sewage samples collected from southern Israel and tested by reference culture based methods were used for analytical validation of the assay's performance. The limit of detection of the multiplex qRT-PCR (SOAS/MS-2) assay was 0.1 plaque-forming unit (pfu)/reaction (20 pfu/mL) for WPV1-SOAS RNA with 100% sensitivity, specificity, positive and negative predictive values when compared to the culture based method. The turnaround time was rapid, providing results for environmental samples within 24 to 48 hours from completion of sewage processing, instead of five to seven days by culture-based analysis. Direct sewage testing by qRT-PCR assay proved to be a useful tool for rapid detection and environmental surveillance of WPV1-SOAS circulating strain during emergency response. Application of the approach for detection of WPV1-SOAS in stool samples obtained during acute flaccid paralysis (AFP) surveillance or field surveys should be further evaluated.

Intensified environmental surveillance supporting the response to wild poliovirus type 1 silent circulation in Israel, 2013.

An emergency response was triggered by recovery of wild poliovirus type 1 (WPV1) of the South Asia (SOAS) lineage from sewage in southern Israel in April 2013 during routine environmental surveillance. Public health risk assessment necessitated intensification of environmental surveillance in order to facilitate countrywide monitoring of WPV1-SOAS circulation. This involved increasing sampling frequency and broadening the geographical area, for better coverage of the population at risk, as well as modifying sewage testing algorithms to accommodate a newly developed WPV1-SOAS-specific quantitative real-time RT-PCR assay for screening of RNA extracted directly from sewage concentrates, in addition to standard virus isolation. Intensified surveillance in 74 sites across Israel between 1 February and 31 August 2013 documented a sustained high viral load of WPV1-SOAS in sewage samples from six Bedouin settlements and two cities with Jewish and Arab populations in the South district. Lower viral loads and intermittent detection were documented in sampling sites representing 14 mixed communities in three of the five health districts in central and northern Israel. Environmental surveillance plays a fundamental role in routine monitoring of WPV circulation in polio-free countries. The rapid assay specific for the circulating strain facilitated implementation of intensified surveillance and informed the public health response and decision-making.

Oral hygiene habits, dental home, and toothbrushing among immigrant and native low socioeconomic class populations.

UNLABELLED: About 45,000 people immigrated to Israel from Ethiopia over the last 30 years. The purpose of this study was to compare oral hygiene habits in preschool children from low socioeconomic neighborhoods offspring of immigrants from Ethiopia to offspring of native Israelis. METHOD: Parents of children attending 21 nursery schools were asked to respond anonymously to 7 questions about their children's visits to a dentist and toothbrushing habits. RESULTS: Parents of 719 children (382 Ethiopian and 337 native Israeli) responded. Of children aged 49-82 months, 15% offspring of Ethiopian and 25% of native Israelis were reported to have visited a dentist; and 45% and 65%, respectively, to brush their teeth at least once daily. More than 90% of children of both populations were reported to have toothbrushes. Of children aged 18-48 months, 28% of Ethiopian and 65% of native Israelis were reported to brush their teeth at least once daily. CONCLUSION: After more than 20 years residence in a new country, the dental home of an immigrant population was significantly different from that of the native population, of the same low socioeconomic neighborhoods. Discrepancies in parental responses highlight the importance of addressing information bias.

[Esthetic restorations of primary anterior teeth].

Esthetic treatment of primary teeth is one of the greatest challenges to pediatric dentists. A variety of restorative options using full coverage are available for anterior primary teeth. In the last half century the emphasis on treatment of severely decayed primary teeth shifted from extraction to restoration. In the past, restorations consisted of placement of stainless steel crowns on severely decayed teeth. However, they are esthetically unacceptable today. Over the last decade parents expect a higher esthetic standard for their children's primary teeth. Thus, the restoration should provide esthetic appearance and durability in addition to restoring function. The purpose of this review is to describe the types of full coverage options for anterior primary teeth currently available.

Weight change and mental health status in a behavioral weight loss trial.

BACKGROUND: Obesity, depression, and anxiety often co-occur, but research on weight change and mental health status is limited. This analysis examined how the mental component score (MCS-12) from the Short Form health survey changed over 24 months in weight loss trial participants with vs. without treatment seeking for affective symptoms (TxASx) and by weight change quintiles. METHODS: Participants with complete data (n = 1163) were analyzed from enrollees in a cluster-randomized, behavioral weight loss trial in rural U.S. Midwestern primary care practices. Participants received a lifestyle intervention with different delivery models, including in-clinic individual, in-clinic group, or telephone group counseling visits. Participants were stratified by baseline TxASx status and 24-month weight change quintiles. Mixed models were used to estimate MCS-12 scores. RESULTS: There was a significant group-by-time interaction at the 24-month follow-up. The largest 0-24 month increase in MCS-12 scores (+5.3 points [12 %]) was observed in participants with TxASx who lost the most weight during the trial, while the largest decrease in MCS-12 scores (-1.8 points [-3 %]) was observed in participants without TxASx who gained the most weight (p < 0.001). LIMITATIONS: Notable limitations included self-reported mental health, the observational analytical design, and a largely homogenous source population, as well as the possibility of reverse causation biasing some findings. CONCLUSIONS: Mental health status generally improved, particularly among participants with TxASx who experienced significant weight loss. Those without TxASx who gained weight, however, had a decline in mental health status over 24 months. Replication of these findings is warranted.

Above and below-ground growth, accumulated dry matter and nitrogen remobilization of wheat (Triticum aestivum) genotypes grown in PVC tubes under well- and deficit-watered conditions.

The continuing decline in water resources under the ever-changing climate compels us to re-orient our focus to a more sustainable practice. This study investigates the performance of Triticum aestivum wheat genotypes viz. HD-2967, HD-3086, HD-3249, DBW-187, and HD-3226 under well- and deficit-watered conditions for their root-traits, biomass and nitrogen accumulation and remobilization, and water use efficiencies, grown in PVC-tubes. The genotypes HD-2967, HD-3086, HD-3249, DBW-187, and HD-3226 under well-watered (WW) resulted in 36, 35, 38, 33, and 42% more grain yield compared to deficit-watered (DW). Among the genotypes, HD-3249 had the highest grain yield under both well- and deficit-watered conditions. Compared to DW, the WW had 28%, 30%, and 28% greater root length, biomass, and root length density at flowering {102 days (d), Z61}, while among the genotypes, HD-3249 had relatively greater root-traits. At flowering (Z61) and maturity (132 d, Z89), genotypes under WW accumulated 30-46% and 30-53%, respectively greater shoot biomass over the DW. Furthermore, the shoot biomass remobilised for HD-2967, HD-3086, HD-3249, DBW-187, and HD-3226 under the WW was 32, 37, 39, 35, and 35% greater than the DW. The nitrogen partitioning to different plant parts at flowering (Z61) and maturity (Z89) was significantly greater with the WW than with DW. The total nitrogen- remobilized and contribution to grain-N under the WW was 55, 58, 52, 53, 58% and 9, 19, 15, 17, 17% greater than the DW for the genotypes HD-2967, HD-3086, HD-3249, DBW-187, and HD-3226. The irrigation water use efficiency (WUE) at flowering (Z61) was more under the deficit-watered, but the biomass and grain total WUE was improved with the well-watered condition. Hence, it is apparent that proper scheduling of irrigation and N applications, along with the adoption of a genotype suited to a particular environment, will result in better WUE and grain yields, along with better utilization of scarce resources.

Construction of a multisite DataLink using electronic health records for the identification, surveillance, prevention, and management of diabetes mellitus: the SUPREME-DM project.

INTRODUCTION: Electronic health record (EHR) data enhance opportunities for conducting surveillance of diabetes. The objective of this study was to identify the number of people with diabetes from a diabetes DataLink developed as part of the SUPREME-DM (SUrveillance, PREvention, and ManagEment of Diabetes Mellitus) project, a consortium of 11 integrated health systems that use comprehensive EHR data for research. METHODS: We identified all members of 11 health care systems who had any enrollment from January 2005 through December 2009. For these members, we searched inpatient and outpatient diagnosis codes, laboratory test results, and pharmaceutical dispensings from January 2000 through December 2009 to create indicator variables that could potentially identify a person with diabetes. Using this information, we estimated the number of people with diabetes and among them, the number of incident cases, defined as indication of diabetes after at least 2 years of continuous health system enrollment. RESULTS: The 11 health systems contributed 15,765,529 unique members, of whom 1,085,947 (6.9%) met 1 or more study criteria for diabetes. The nonstandardized proportion meeting study criteria for diabetes ranged from 4.2% to 12.4% across sites. Most members with diabetes (88%) met multiple criteria. Of the members with diabetes, 428,349 (39.4%) were incident cases. CONCLUSION: The SUPREME-DM DataLink is a unique resource that provides an opportunity to conduct comparative effectiveness research, epidemiologic surveillance including longitudinal analyses, and population-based care management studies of people with diabetes. It also provides a useful data source for pragmatic clinical trials of prevention or treatment interventions.