Conservative and disruptive modes of adolescent change in human brain functional connectivity

Adolescent changes in human brain function are not entirely understood. Here, we used multiecho functional MRI (fMRI) to measure developmental change in functional connectivity (FC) of resting-state oscillations between pairs of 330 cortical regions and 16 subcortical regions in 298 healthy adolescents scanned 520 times. Participants were aged 14 to 26 y and were scanned on 1 to 3 occasions at least 6 mo apart. We found 2 distinct modes of age-related change in FC: “conservative” and “disruptive.” Conservative development was characteristic of primary cortex, which was strongly connected at 14 y and became even more connected in the period from 14 to 26 y. Disruptive development was characteristic of association cortex and subcortical regions, where connectivity was remodeled: connections that were weak at 14 y became stronger during adolescence, and connections that were strong at 14 y became weaker. These modes of development were quantified using the maturational index (MI), estimated as Spearman’s correlation between edgewise baseline FC (at 14 y, FC14) and adolescent change in FC (ΔFC14−26), at each region. Disruptive systems (with negative MI) were activated by social cognition and autobiographical memory tasks in prior fMRI data and significantly colocated with prior maps of aerobic glycolysis (AG), AG-related gene expression, postnatal cortical surface expansion, and adolescent shrinkage of cortical thickness. The presence of these 2 modes of development was robust to numerous sensitivity analyses. We conclude that human brain organization is disrupted during adolescence by remodeling of FC between association cortical and subcortical areas

Complementary and alternative medical therapy utilization by people with chronic fatiguing illnesses in the United States

<p>Abstract</p> <p>Background</p> <p>Chronic fatiguing illnesses, including chronic fatigue syndrome (CFS), pose a diagnostic and therapeutic challenge. Previous clinical reports addressed the utilization of health care provided to patients with CFS by a variety of practitioners with other than allopathic training, but did not examine the spectrum of complementary and alternative medicine (CAM) therapies used. This study was designed to measure CAM therapy use by persons with fatiguing illnesses in the United States population.</p> <p>Methods</p> <p>During a random-digit dialing survey to estimate the prevalence of CFS-like illness in urban and rural populations from different geographic regions of the United States, we queried the utilization of CAM including manipulation or body-based therapies, alternative medical systems, mind-body, biologically-based, and energy modalities.</p> <p>Results</p> <p>Four hundred forty fatigued and 444 non-fatigued persons from 2,728 households completed screening. Fatigued subjects included 53 persons with prolonged fatigue, 338 with chronic fatigue, and 49 with CFS-like illness. Mind-body therapy (primarily personal prayer and prayer by others) was the most frequently used CAM across all groups. Among women, there was a significant trend of increasing overall CAM use across all subgroups (p-trend = 0.003). All categories of CAM use were associated with significantly poorer physical health scores, and all but one (alternative medicine systems) were associated with significantly poorer mental health scores. People with CFS-like illness were significantly more likely to use body-based therapy (chiropractic and massage) than non-fatigued participants (OR = 2.52, CI = 1.32, 4.82). Use of body-based therapies increased significantly in a linear trend across subgroups of non-fatigued, prolonged fatigued, chronic fatigued, and CFS-like subjects (p-trend = 0.002). People with chronic fatigue were also significantly more likely to use body-based therapy (OR = 1.52, CI = 1.07, 2.16) and mind-body (excluding prayer) therapy than non-fatigued participants (OR = 1.73, CI = 1.20 – 2.48).</p> <p>Conclusion</p> <p>Utilization of CAM was common in fatiguing illnesses, and was largely accounted for by the presence of underlying conditions and poor physical and mental health. Compared to non-fatigued persons, those with CFS-like illness or chronic fatigue were most likely to use body-based and mind-body therapies. These observations have important implications for provider education programs and development of intervention strategies for CFS.</p

Tissue Specific Profiling of Females of Schistosoma japonicum by Integrated Laser Microdissection Microscopy and Microarray Analysis

Schistosomes are parasitic worms responsible for important human diseases in tropical and developing nations. There is urgent need to develop new drugs and vaccines to augment current treatments for this disease. In recent years, concerted efforts by many laboratories have led to extensive genetic sequencing of the parasites, and the publication of genome sequence for two agents of schistosomiasis appears imminent. This genetic information has revealed many molecules expressed by the schistosome parasites for which no functional information is available. This lack of information extends to ignorance of where in the complex multicellular schistosome parasites the genes are expressed. We integrated two molecular and cellular techniques to address these knowledge gaps. We used laser microdissection microscopy to dissect small but highly important tissues involved in nutrition and reproduction from sections of female Schistosoma japonicum. From these dissected tissues we then used a broad molecular biology method to identify the multiple genes active in these tissues. Our approach has allowed us to formulate the basis of a “gene atlas” for schistosome parasites, defining the expression repertoire of specific tissues. The better understanding of the roles of tissues in parasite biology, especially in development, reproduction and interactions with its human hosts, should promote future investigations into pathogenesis and control of these significant parasites

Recent advances in gastrointestinal oncology - updates and insights from the 2009 annual meeting of the American Society of Clinical Oncology

We have reviewed the pivotal presentations related to gastrointestinal malignancies from 2009 annual meeting of the American Society of Clinical Oncology with the theme of "personalizing cancer care". We have discussed the scientific findings and the impact on practice guidelines and ongoing clinical trials. Adding trastuzumab to chemotherapy improved the survival of patients with advanced gastric cancer overexpressing human epidermal growth factor receptor 2. Gemcitabine plus cisplatin has become a new standard for first-line treatment of advanced biliary cancer. Octreotide LAR significantly lengthened median time to tumor progression compared with placebo in patients with metastatic neuroendocrine tumors of the midgut. Addition of oxaliplatin to fluoropyrimidines for preoperative chemoradiotherapy in patients with stage II or III rectal cancer did not improve local tumor response but increased toxicities. Bevacizumab did not provide additional benefit to chemotherapy in adjuvant chemotherapy for stage II or III colon cancer. In patients with resected stage II colon cancer, recurrence score estimated by multigene RT-PCR assay has been shown to provide additional risk stratification. In stage IV colorectal cancer, data have supported the routine use of prophylactic skin treatment in patients receiving antibody against epidermal growth factor receptor, and the use of upfront chemotherapy as initial management in patients with synchronous metastasis without obstruction or bleeding from the primary site

Ribosome-Dependent ATPase Interacts with Conserved Membrane Protein in Escherichia coli to Modulate Protein Synthesis and Oxidative Phosphorylation

Elongation factor RbbA is required for ATP-dependent deacyl-tRNA release presumably after each peptide bond formation; however, there is no information about the cellular role. Proteomic analysis in Escherichia coli revealed that RbbA reciprocally co-purified with a conserved inner membrane protein of unknown function, YhjD. Both proteins are also physically associated with the 30S ribosome and with members of the lipopolysaccharide transport machinery. Genome-wide genetic screens of rbbA and yhjD deletion mutants revealed aggravating genetic interactions with mutants deficient in the electron transport chain. Cells lacking both rbbA and yhjD exhibited reduced cell division, respiration and global protein synthesis as well as increased sensitivity to antibiotics targeting the ETC and the accuracy of protein synthesis. Our results suggest that RbbA appears to function together with YhjD as part of a regulatory network that impacts bacterial oxidative phosphorylation and translation efficiency

Galectin-1 Is Part of Human Trophoblast Invasion Machinery - A Functional Study In Vitro

Interactions of glycoconjugates with endogenous galectins, have been long proposed to participate in several reproductive processes including implantation. In human placenta gal-1, gal-3, gal-8, and gal-13 proteins are known to be present. Each of them has been proposed to play multiple functions, but so far no clear picture has emerged. We hypothesized that gal-1 participates in trophoblast invasion, and conducted Matrigel invasion assay using isolated cytotrophoblast from first trimester placenta and HTR-8/SVneo cell line to test it.<0.001) by Ox-gal-1 at 1 µg/ml. Both sets of results confirmed involvement of gal-1 in trophoblast invasion. Galectin profile of isolated cytotrophoblast and HTR-8/SVneo cells was established using RT-PCR and real-time PCR and found to consist of gal-1, gal-3 and gal-8 for both cell types. Only gal-1 was located at the trophoblast cell membrane, as determined by FACS analysis, which is consistent with the results of the functional tests.These findings qualify gal-1 as a member of human trophoblast cell invasion machinery

Atomoxetine Enhances Connectivity of Prefrontal Networks in Parkinson's Disease.

Cognitive impairment is common in Parkinson's disease (PD), but often not improved by dopaminergic treatment. New treatment strategies targeting other neurotransmitter deficits are therefore of growing interest. Imaging the brain at rest ('task-free') provides the opportunity to examine the impact of a candidate drug on many of the brain networks that underpin cognition, while minimizing task-related performance confounds. We test this approach using atomoxetine, a selective noradrenaline reuptake inhibitor that modulates the prefrontal cortical activity and can facilitate some executive functions and response inhibition. Thirty-three patients with idiopathic PD underwent task-free fMRI. Patients were scanned twice in a double-blind, placebo-controlled crossover design, following either placebo or 40-mg oral atomoxetine. Seventy-six controls were scanned once without medication to provide normative data. Seed-based correlation analyses were used to measure changes in functional connectivity, with the right inferior frontal gyrus (IFG) a critical region for executive function. Patients on placebo had reduced connectivity relative to controls from right IFG to dorsal anterior cingulate cortex and to left IFG and dorsolateral prefrontal cortex. Atomoxetine increased connectivity from the right IFG to the dorsal anterior cingulate. In addition, the atomoxetine-induced change in connectivity from right IFG to dorsolateral prefrontal cortex was proportional to the change in verbal fluency, a simple index of executive function. The results support the hypothesis that atomoxetine may restore prefrontal networks related to executive functions. We suggest that task-free imaging can support translational pharmacological studies of new drug therapies and provide evidence for engagement of the relevant neurocognitive systems.This work was funded by the Wellcome trust (103838), Parkinson’s UK, National Institute for Health Research’s Cambridge Biomedical Research Centre and the Medical Research Council (MC_US_A060_0016 and RG62761) and the James F McDonnell Foundation (21st century science initiative on Understanding Human Cognition). The BCNI is supported by a joint award from the Wellcome Trust and Medical Research Council.This is the final version of the article. It first appeared from Nature Publishing Group via http://dx.doi.org/10.1038/npp.2016.1

Computerized clinical decision support systems for therapeutic drug monitoring and dosing: A decision-maker-researcher partnership systematic review

<p>Abstract</p> <p>Background</p> <p>Some drugs have a narrow therapeutic range and require monitoring and dose adjustments to optimize their efficacy and safety. Computerized clinical decision support systems (CCDSSs) may improve the net benefit of these drugs. The objective of this review was to determine if CCDSSs improve processes of care or patient outcomes for therapeutic drug monitoring and dosing.</p> <p>Methods</p> <p>We conducted a decision-maker-researcher partnership systematic review. Studies from our previous review were included, and new studies were sought until January 2010 in MEDLINE, EMBASE, Evidence-Based Medicine Reviews, and Inspec databases. Randomized controlled trials assessing the effect of a CCDSS on process of care or patient outcomes were selected by pairs of independent reviewers. A study was considered to have a positive effect (<it>i.e.</it>, CCDSS showed improvement) if at least 50% of the relevant study outcomes were statistically significantly positive.</p> <p>Results</p> <p>Thirty-three randomized controlled trials were identified, assessing the effect of a CCDSS on management of vitamin K antagonists (14), insulin (6), theophylline/aminophylline (4), aminoglycosides (3), digoxin (2), lidocaine (1), or as part of a multifaceted approach (3). Cluster randomization was rarely used (18%) and CCDSSs were usually stand-alone systems (76%) primarily used by physicians (85%). Overall, 18 of 30 studies (60%) showed an improvement in the process of care and 4 of 19 (21%) an improvement in patient outcomes. All evaluable studies assessing insulin dosing for glycaemic control showed an improvement. In meta-analysis, CCDSSs for vitamin K antagonist dosing significantly improved time in therapeutic range.</p> <p>Conclusions</p> <p>CCDSSs have potential for improving process of care for therapeutic drug monitoring and dosing, specifically insulin and vitamin K antagonist dosing. However, studies were small and generally of modest quality, and effects on patient outcomes were uncertain, with no convincing benefit in the largest studies. At present, no firm recommendation for specific systems can be given. More potent CCDSSs need to be developed and should be evaluated by independent researchers using cluster randomization and primarily assess patient outcomes related to drug efficacy and safety.</p

Constraints on models of the Higgs boson with exotic spin and parity using decays to bottom-antibottom quarks in the full CDF data set

A search for particles with the same mass and couplings as those of the standard model Higgs boson but different spin and parity quantum numbers is presented. We test two specific alternative Higgs boson hypotheses: a pseudoscalar Higgs boson with spin-parity JP=0- and a gravitonlike Higgs boson with JP=2+, assuming for both a mass of 125GeV/c2. We search for these exotic states produced in association with a vector boson and decaying into a bottom-antibottom quark pair. The vector boson is reconstructed through its decay into an electron or muon pair, or an electron or muon and a neutrino, or it is inferred from an imbalance in total transverse momentum. We use expected kinematic differences between events containing exotic Higgs bosons and those containing standard model Higgs bosons. The data were collected by the CDF experiment at the Tevatron proton-antiproton collider, operating at a center-of-mass energy of s=1.96TeV, and correspond to an integrated luminosity of 9.45fb-1. We exclude deviations from the predictions of the standard model with a Higgs boson of mass 125GeV/c2 at the level of 5 standard deviations, assuming signal strengths for exotic boson production equal to the prediction for the standard model Higgs boson, and set upper limits of approximately 30% relative to the standard model rate on the possible rate of production of each exotic state