Abstract Purpose Depression commonly accompanies diabetes, resulting in reduced adherence to medications and increased risk for morbidity and mortality. The objective of this study was to examine ...whether a simple, brief integrated approach to depression and type 2 diabetes mellitus (type 2 diabetes) treatment improved adherence to oral hypoglycemic agents and antidepressant medications, glycemic control, and depression among primary care patients. Methods We undertook a randomized controlled trial conducted from April 2010 through April 2011 of 180 patients prescribed pharmacotherapy for type 2 diabetes and depression in primary care. Patients were randomly assigned to an integrated care intervention or usual care. Integrated care managers collaborated with physicians to offer education and guideline-based treatment recommendations and to monitor adherence and clinical status. Adherence was assessed using the Medication Event Monitoring System (MEMS). We used glycated hemoglobin (HbA1c ) assays to measure glycemic control and the 9-item Patient Health Questionnaire (PHQ-9) to assess depression. Results Intervention and usual care groups did not differ statistically on baseline measures. Patients who received the intervention were more likely to achieve HbA1c levels of less than 7% (intervention 60.9% vs usual care 35.7%; P <.001) and remission of depression (PHQ-9 score of less than 5: intervention 58.7% vs usual care 30.7%; P <.001) in comparison with patients in the usual care group at 12 weeks. Conclusions A randomized controlled trial of a simple, brief intervention integrating treatment of type 2 diabetes and depression was successful in improving outcomes in primary care. An integrated approach to depression and type 2 diabetes treatment may facilitate its deployment in real-world practices with competing demands for limited resources.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
The aim of this study was to assess potential candidate gene regions and corresponding universal primer pairs as secondary DNA barcodes for the fungal kingdom, additional to ITS rDNA as primary ...barcode. Amplification efficiencies of 14 (partially) universal primer pairs targeting eight
genetic markers were tested across > 1 500 species (1 931 strains or specimens) and the outcomes of almost twenty thousand (19 577) polymerase chain reactions were evaluated. We tested several well-known primer pairs that amplify: i) sections of the nuclear ribosomal RNA gene large subunit
(D1-D2 domains of 26/28S); ii) the complete internal transcribed spacer region (ITS1/2); iii) partial β-tubulin II (TUB2); iv) γ-actin (ACT); v) translation elongation factor 1-α (TEF1α); and vi) the second largest subunit of RNA-polymerase
II (partial RPB2, section 5-6). Their PCR efficiencies were compared with novel candidate primers corresponding to: i) the fungal-specific translation elongation factor 3 (TEF3); ii) a small ribosomal protein necessary for t-RNA docking; iii) the 60S L10 (L1) RP;
iv) DNA topoisomerase I (TOPI); v) phosphoglycerate kinase (PGK); vi) hypothetical protein LNS2; and vii) alternative sections of TEF1α. Results showed that several gene sections are accessible to universal primers (or primers universal for phyla) yielding
a single PCR-product. Barcode gap and multi-dimensional scaling analyses revealed that some of the tested candidate markers have universal properties providing adequate infra- and inter-specific variation that make them attractive barcodes for species identification. Among these gene sections,
a novel high fidelity primer pair for TEF1α, already widely used as a phylogenetic marker in mycology, has potential as a supplementary DNA barcode with superior resolution to ITS. Both TOPI and PGK show promise for the Ascomycota, while TOPI and LNS2
are attractive for the Pucciniomycotina, for which universal primers for ribosomal subunits often fail.
Summary Tumours respond differently to immunotherapies compared with chemotherapeutic drugs, raising questions about the assessment of changes in tumour burden—a mainstay of evaluation of cancer ...therapeutics that provides key information about objective response and disease progression. A consensus guideline—iRECIST—was developed by the RECIST working group for the use of modified Response Evaluation Criteria in Solid Tumours (RECIST version 1.1) in cancer immunotherapy trials, to ensure consistent design and data collection, facilitate the ongoing collection of trial data, and ultimate validation of the guideline. This guideline describes a standard approach to solid tumour measurements and definitions for objective change in tumour size for use in trials in which an immunotherapy is used. Additionally, it defines the minimum datapoints required from future trials and those currently in development to facilitate the compilation of a data warehouse to use to later validate iRECIST. An unprecedented number of trials have been done, initiated, or are planned to test new immune modulators for cancer therapy using a variety of modified response criteria. This guideline will allow consistent conduct, interpretation, and analysis of trials of immunotherapies.
In recent years, puberty suppression by means of gonadotropin-releasing hormone analogs has become accepted in clinical management of adolescents who have gender dysphoria (GD). The current study is ...the first longer-term longitudinal evaluation of the effectiveness of this approach.
A total of 55 young transgender adults (22 transwomen and 33 transmen) who had received puberty suppression during adolescence were assessed 3 times: before the start of puberty suppression (mean age, 13.6 years), when cross-sex hormones were introduced (mean age, 16.7 years), and at least 1 year after gender reassignment surgery (mean age, 20.7 years). Psychological functioning (GD, body image, global functioning, depression, anxiety, emotional and behavioral problems) and objective (social and educational/professional functioning) and subjective (quality of life, satisfaction with life and happiness) well-being were investigated.
After gender reassignment, in young adulthood, the GD was alleviated and psychological functioning had steadily improved. Well-being was similar to or better than same-age young adults from the general population. Improvements in psychological functioning were positively correlated with postsurgical subjective well-being.
A clinical protocol of a multidisciplinary team with mental health professionals, physicians, and surgeons, including puberty suppression, followed by cross-sex hormones and gender reassignment surgery, provides gender dysphoric youth who seek gender reassignment from early puberty on, the opportunity to develop into well-functioning young adults.
Highlights • Neoadjuvant radiotherapy is administered only for rectal cancer. • There is a lack of robust evidence for adjuvant chemotherapy in rectal cancer. • Rectal and colon cancer harbor a ...different composition of potential drug targets. • Rectal and colon cancer differ in their metastatic patterns. • Metastatic rectal and colon cancer are commonly treated alike.
Recent research in nitrogen exchange with the atmosphere has separated research communities according to N form. The integrated perspective needed to quantify the net effect of N on greenhouse-gas ...balance is being addressed by the NitroEurope Integrated Project (NEU). Recent advances have depended on improved methodologies, while ongoing challenges include gas–aerosol interactions, organic nitrogen and N
2 fluxes. The NEU strategy applies a 3-tier Flux Network together with a Manipulation Network of global-change experiments, linked by common protocols to facilitate model application. Substantial progress has been made in modelling N fluxes, especially for N
2O, NO and bi-directional NH
3 exchange. Landscape analysis represents an emerging challenge to address the spatial interactions between farms, fields, ecosystems, catchments and air dispersion/deposition. European up-scaling of N fluxes is highly uncertain and a key priority is for better data on agricultural practices. Finally, attention is needed to develop N flux verification procedures to assess compliance with international protocols.
Current N research is separated by form; the challenge is to link N components, scales and issues.
Dual-specificity tyrosine-(Y)-phosphorylation-regulated kinase 1 A (DYRK1A) maps to the Down syndrome critical region; copy number increase of this gene is thought to have a major role in the ...neurocognitive deficits associated with Trisomy 21. Truncation of DYRK1A in patients with developmental delay (DD) and autism spectrum disorder (ASD) suggests a different pathology associated with loss-of-function mutations. To understand the phenotypic spectrum associated with DYRK1A mutations, we resequenced the gene in 7162 ASD/DD patients (2446 previously reported) and 2169 unaffected siblings and performed a detailed phenotypic assessment on nine patients. Comparison of our data and published cases with 8696 controls identified a significant enrichment of DYRK1A truncating mutations (P=0.00851) and an excess of de novo mutations (P=2.53 × 10(-10)) among ASD/intellectual disability (ID) patients. Phenotypic comparison of all novel (n=5) and recontacted (n=3) cases with previous case reports, including larger CNV and translocation events (n=7), identified a syndromal disorder among the 15 patients. It was characterized by ID, ASD, microcephaly, intrauterine growth retardation, febrile seizures in infancy, impaired speech, stereotypic behavior, hypertonia and a specific facial gestalt. We conclude that mutations in DYRK1A define a syndromic form of ASD and ID with neurodevelopmental defects consistent with murine and Drosophila knockout models.
To understand how the brain processes sensory information to guide behavior, we must know how stimulus representations are transformed throughout the visual cortex. Here we report an open, ...large-scale physiological survey of activity in the awake mouse visual cortex: the Allen Brain Observatory Visual Coding dataset. This publicly available dataset includes the cortical activity of nearly 60,000 neurons from six visual areas, four layers, and 12 transgenic mouse lines in a total of 243 adult mice, in response to a systematic set of visual stimuli. We classify neurons on the basis of joint reliabilities to multiple stimuli and validate this functional classification with models of visual responses. While most classes are characterized by responses to specific subsets of the stimuli, the largest class is not reliably responsive to any of the stimuli and becomes progressively larger in higher visual areas. These classes reveal a functional organization wherein putative dorsal areas show specialization for visual motion signals.
Abstract The aim of the current study was to examine the effectiveness of a school-centered multicomponent PA intervention, called ‘Active Living’, on children's daily PA levels. A quasi-experimental ...design was used including 9 intervention schools and 9 matched control schools located in the Netherlands. The baseline measurement took place between March–June 2013, and follow-up measurements were conducted 12 months afterwards. Accelerometer (ActiGraph, GT3X +) data of 520 children aged 8–11 years were collected and supplemented with demographics and weather conditions data. Implementation magnitude of the interventions was measured by keeping logbooks on the number of implemented physical environmental interventions (PEIs) and social environmental interventions (SEIs). Multilevel multivariate linear regression analyses were used to study changes in sedentary behavior (SB), light physical activity (LPA) and moderate-to-vigorous physical activity (MVPA) between baseline and follow-up. Finally, effect sizes (ESs) were calculated using Cohen's d. No pooled effects on PA and SB were found between children exposed and not exposed to Active Living after 12 months. However, children attending Active Living schools that implemented larger numbers of both PEIs and SEIs engaged in 15 more minutes of LPA per weekday at follow-up than children in the control condition (ES = 0.41; p < .05). Moreover, children attending these schools spent less time in SB at follow-up (ES = 0.33), although this effect was non-significant. No significant effects were found on MVPA. A school-centered multicomponent PA intervention holds the potential to activate children, but a comprehensive set of intervention elements with a sufficient magnitude is necessary to achieve at least moderate effect sizes.
OBJECTIVE—Because late vein graft failure is caused by intimal hyperplasia (IH) and accelerated atherosclerosis, and these processes are thought to be inflammation driven, influx of monocytes is one ...of the first phenomena seen in IH, we would like to provide direct evidence for a role of the MCP-1 pathway in the development of vein graft disease.
METHODS AND RESULTS—MCP-1 expression is demonstrated in various stages of vein graft disease in a murine model in which venous interpositions are placed in the carotid arteries of hypercholesterolemic ApoE3Leiden mice and in cultured human saphenous vein (HSV) segments in which IH occurs. The functional involvement of MCP-1 in vein graft remodeling is demonstrated by blocking the MCP-1 receptor CCR-2 using 7ND-MCP-1. 7ND-MCP1 gene transfer resulted in 51% reduction in IH in the mouse model, when compared with controls. In HSV cultures neointima formation was inhibited by 53%. In addition, we demonstrate a direct inhibitory effect of 7ND-MCP-1 on the proliferation of smooth muscle cell (SMC) in HSV cultures and in SMC cell cultures.
CONCLUSION—These data, for the first time, prove that MCP-1 has a pivotal role in vein graft thickening due to intimal hyperplasia and accelerated atherosclerosis.
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