Intrinsic Frontolimbic Connectivity and Mood Symptoms in Young Adult Cannabis Users.

Objective: The endocannbinoid system and cannabis exposure has been implicated in emotional processing. The current study examined whether regular cannabis users demonstrated abnormal intrinsic (a.k.a. resting state) frontolimbic connectivity compared to non-users. A secondary aim examined the relationship between cannabis group connectivity differences and self-reported mood and affect symptoms. Method: Participants included 79 cannabis-using and 80 non-using control emerging adults (ages of 18-30), balanced for gender, reading ability, and age. Standard multiple regressions were used to predict if cannabis group status was associated with frontolimbic connectivity after controlling for site, past month alcohol and nicotine use, and days of abstinence from cannabis. Results: After controlling for research site, past month alcohol and nicotine use, and days of abstinence from cannabis, cannabis users demonstrated significantly greater connectivity between left rACC and the following: right rACC (p = 0.001; corrected p = 0.05; f 2 = 0.55), left amygdala (p = 0.03; corrected p = 0.47; f 2 = 0.17), and left insula (p = 0.03; corrected p = 0.47; f 2 = 0.16). Among cannabis users, greater bilateral rACC connectivity was significantly associated with greater subthreshold depressive symptoms (p = 0.02). Conclusions: Cannabis using young adults demonstrated greater connectivity within frontolimbic regions compared to controls. In cannabis users, greater bilateral rACC intrinsic connectivity was associated with greater levels of subthreshold depression symptoms. Current findings suggest that regular cannabis use during adolescence is associated with abnormal frontolimbic connectivity, especially in cognitive control and emotion regulation regions

Baseline characteristics and patient reported outcome data of patients prescribed etanercept: web-based and telephone evaluation

<p>Background: The anti-TNF inhibitor, etanercept is administered as a once or twice weekly subcutaneous injection for the treatment of rheumatoid arthritis, psoriasis, ankylosing spondylitis, psoriatic arthritis and juvenile idiopathic arthritis (JIA). Limited data from the patients' perspective are available on the use of biologics in the treatment of these chronic conditions and this evaluation was designed to collect data from patients who had been prescribed etanercept for the first time. This manuscript describes the self-reported baseline characteristics and health-related quality of life of patients prior to treatment. Follow-up data will be reported separately.</p> <p>Methods: Patients throughout the United Kingdom prescribed etanercept were invited to participate in an evaluation of their condition and treatment using a data collection tool consisting of a web-based system supplemented by telephone reporting (PROBE). Outcome measures reported at baseline included demographic data, the condition being treated, previous treatment with biologic agents and current and previous medications. Questions modified from standard, validated quality of life questionnaires such as EQ-5D were incorporated and patients made a global assessment of the severity of their own illness using the CGI-S scale.</p> <p>Results: A total of 344 patients/carers/parents participated in the evaluation at baseline, 290 (84%) by online questionnaire and 54 (16%) by telephone. Overall, the study population had a mean age of 53 years, was predominantly female (62%) and 20% had been previously treated with a biologic agent. A total of 191 (56%) patients were receiving treatment with etanercept for rheumatoid arthritis, 44 (13%) for psoriatic arthritis, 43 (13%) for ankylosing spondylitis, 35 (10%) for psoriasis, 9 (3%) for known juvenile idiopathic arthritis (JIA) and 22 (6%) for another condition/patient unsure/missing response. All patients were prescribed the 50 mg weekly dose of etanercept except for 1 patient with JIA (40 mg) dose and 2 patients with psoriasis (100 mg). Thirty-eight percent of patients with rheumatoid arthritis were not receiving treatment with methotrexate.</p> <p>Conclusions: The baseline characteristics and health-related quality of life of first time users of etanercept can be adequately described using self-reported patient data collected using an online questionnaire with a telephone option (PROBE).</p&gt

Prevention Across the Spectrum: a randomized controlled trial of three programs to reduce risk factors for both eating disorders and obesity

Author version made available in accordance with publisher copyright policy.Background: A randomized-controlled trial (RCT) of 3 school-based programs and a no intervention control group was conducted to evaluate their efficacy in reducing eating disorder and obesity risk factors. Methods: N = 1,316 Grade 7 and 8 girls and boys (M age = 13.21 years) across three Australian states were randomly allocated to: Media Smart; Life Smart; Helping, Encouraging, Listening and Protecting Peers Initiative (HELPP) or control (usual school class). Risk factors were measured at baseline, post-program (5-weeks later), and 6- and 12-month follow-up. Results: Media Smart girls had half the rate of onset of clinically significant concerns about shape and weight than control girls at 12-month follow-up. Media Smart and HELPP girls reported significantly lower weight and shape concern than Life Smart girls at 12-month follow-up. Media Smart and control girls scored significantly lower than HELPP girls on eating concerns and perceived pressure at 6-month follow-up. Media Smart and HELPP boys experienced significant benefit on media internalization compared to control boys and these were sustained at 12-month follow-up in Media Smart boys. A group x time effect found Media Smart participants reported more physical activity than control and HELPP participants at 6-month follow-up, while a main effect for group found Media Smart participants reported less screen time than controls. Conclusions: Media Smart was the only program to show benefit on both disordered eating and obesity risk factors. Whilst further investigations are indicated, this study suggests that this program is a promising approach to reducing risk factors for both problems

Distinct Contributions of Eroding and Depositional Profiles to Land-Atmosphere CO2 Exchange in Two Contrasting Forests

This work is licensed under a Creative Commons Attribution 4.0 International License.Lateral movements of soil organic C (SOC) influence Earth's C budgets by transporting organic C across landscapes and by modifying soil-profile fluxes of CO2. We extended a previously presented model (Soil Organic C Erosion Replacement and Oxidation, SOrCERO) and present SOrCERODe, a model with which we can project how erosion and subsequent deposition of eroded material can modify biosphere-atmosphere CO2 fluxes in watersheds. The model permits the user to quantify the degree to which eroding and depositional profiles experience a change in SOC oxidation and production as formerly deep horizons become increasingly shallow, and as depositional profiles are buried. To investigate the relative importance of erosion rate, evolving SOC depth distributions, and mineralization reactivity on modeled soil C fluxes, we examine two forests exhibiting distinct depth distributions of SOC content and reactivity, hydrologic regimes and land use. Model projections suggest that, at decadal to centennial timescales: (1) the quantity of SOC moving across a landscape depends on erosion rate and the degree to which SOC production and oxidation at the eroding profile are modified as deeper horizons become shallower, and determines the degree to which depositional profile SOC fluxes are modified; (2) erosional setting C sink strength increases with erosion rate, with some sink effects reaching more than 40% of original profile SOC content after 100 y of a relatively high erosion rate (i.e., 1 mm y−1); (3) even large amounts of deposited SOC may not promote a large depositional profile C sink even with large gains in autochthonous SOC post-deposition if oxidation of buried SOC is not limited; and (4) when modeled depositional settings receive a disproportionately large amount of SOC, simulations of strong C sink scenarios mimic observations of modest preservation of buried SOC and large SOC gains in surficial horizons, suggesting that C sink scenarios have merit in these forests. Our analyses illuminate the importance of cross-landscape linkages between upland and depositional environments for watershed-scale biosphere-atmosphere C fluxes, and emphasize the need for accurate representations and observations of time-varying depth distributions of SOC reactivity across evolving watersheds if we seek accurate projections of ecosystem C balances

Conditional disruption of interactions between Gαi2 and regulator of G protein signaling (RGS) proteins protects the heart from ischemic injury

Abstract Background Regulator of G protein signaling (RGS) proteins suppress G protein coupled receptor signaling by catalyzing the hydrolysis of Gα-bound guanine nucleotide triphosphate. Transgenic mice in which RGS-mediated regulation of Gαi2 is lost (RGS insensitive Gαi2 G184S) exhibit beneficial (protection against ischemic injury) and detrimental (enhanced fibrosis) cardiac phenotypes. This mouse model has revealed the physiological significance of RGS/Gαi2 interactions. Previous studies of the Gαi2 G184S mutation used mice that express this mutant protein throughout their lives. Thus, it is unclear whether these phenotypes result from chronic or acute Gαi2 G184S expression. We addressed this issue by developing mice that conditionally express Gαi2 G184S. Methods Mice that conditionally express RGS insensitive Gαi2 G184S were generated using a floxed minigene strategy. Conditional expression of Gαi2 G184S was characterized by reverse transcription polymerase chain reaction and by enhancement of agonist-induced inhibition of cAMP production in isolated cardiac fibroblasts. The impact of conditional RGS insensitive Gαi2 G184S expression on ischemic injury was assessed by measuring contractile recovery and infarct sizes in isolated hearts subjected to 30 min ischemia and 2 hours reperfusion. Results We demonstrate tamoxifen-dependent expression of Gαi2 G184S, enhanced inhibition of cAMP production, and cardioprotection from ischemic injury in hearts conditionally expressing Gαi2 G184S. Thus the cardioprotective phenotype previously reported in mice expressing Gαi2 G184S does not require embryonic or chronic Gαi2 G184S expression. Rather, cardioprotection occurs following acute (days rather than months) expression of Gαi2 G184S. Conclusions These data suggest that RGS proteins might provide new therapeutic targets to protect the heart from ischemic injury. We anticipate that this model will be valuable for understanding the time course (chronic versus acute) and mechanisms of other phenotypic changes that occur following disruption of interactions between Gαi2 and RGS proteins.http://deepblue.lib.umich.edu/bitstream/2027.42/109553/1/40360_2014_Article_315.pd

How perfectionism and ineffectiveness influence growth of eating disorder risk in young adolescent girls

© 2015. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/. Author version available following 24 month embargo from date of publication (Feb 3 2015) in accordance with publisher copyright policy.Objective: While perfectionism is widely considered to influence risk for eating disorders, results of longitudinal studies are mixed. The goal of the current study was to investigate a more complex model of how baseline perfectionism (both high personal standards and self-critical evaluative concerns) might influence change in risk status for eating disorders in young adolescent girls, through its influence on ineffectiveness. Method: The study was conducted with 926 girls (mean age of 13 years), and involved three waves of data (baseline, 6- and 12-month follow-up). Latent growth curve modeling, incorporating the average rate at which risk changed over time, the intercept (initial status) of ineffectiveness, and baseline perfectionism, was used to explore longitudinal mediation. Results: Personal standards was not supported as contributing to risk but results indicated that the higher mean scores on ineffectiveness over the three waves mediated the relationship between higher baseline self-critical evaluative concerns and both measures of eating disorder risk. The relationship between concern over mistakes and change in risk was small and negative. Discussion: These results suggest the usefulness of interventions related to self-criticism and ineffectiveness for decreasing risk for developing an eating disorder in young adolescent girls

Acute Renal Replacement Therapy in Children with Diarrhea-Associated Hemolytic Uremic Syndrome: A Single Center 16 Years of Experience

Acute kidney injury (AKI) is becoming more prevalent among hospitalized children, its etiologies are shifting, and new treatment modalities are evolving; however, diarrhea-associated hemolytic uremic syndrome (D+HUS) remains the most common primary disease causing AKI in young children. Little has been published about acute renal replacement therapy (ARRT) and its challenges in this population. We describe our single center's experience managing 134 pediatric patients with D+HUS out of whom 58 (43%) required ARRT over the past 16 years. In our cohort, all but one patient were started on peritoneal dialysis (PD). Most patients, 47 (81%), received acute PD on a pediatric inpatient ward. The most common recorded complications in our cohort were peritoneal fluid leaks 13 (22%), peritonitis 11 (20%), and catheter malfunction 5 (9%). Nine patients (16%) needed surgical revision of their PD catheters. There were no bleeding events related to PD despite a mean platelets count of 40.9 (±23.5) × 103/mm3 and rare use of platelets infusions. Despite its methodological limitations, this paper adds to the limited body of evidence supporting the use of acute PD as the primary ARRT modality in children with D+HUS

A Randomized, Controlled Trial of In-Home Drinking Water Intervention to Reduce Gastrointestinal Illness

Trials have provided conflicting estimates of the risk of gastrointestinal illness attributable to tap water. To estimate this risk in an Iowa community with a well-run water utility with microbiologically challenged source water, the authors of this 2000-2002 study randomly assigned blinded volunteers to use externally identical devices (active device: 227 households with 646 persons; sham device: 229 households with 650 persons) for 6 months (cycle A). Each group then switched to the opposite device for 6 months (cycle B). The active device contained a 1-microm absolute ceramic filter and used ultraviolet light. Episodes of highly credible gastrointestinal illness, a published measure of diarrhea, nausea, vomiting, and abdominal cramps, were recorded. Water usage was recorded with personal diaries and an electronic totalizer. The numbers of episodes in cycle A among the active and sham device groups were 707 and 672, respectively; in cycle B, the numbers of episodes were 516 and 476, respectively. In a log-linear generalized estimating equations model using intention-to-treat analysis, the relative rate of highly credible gastrointestinal illness (sham vs. active) for the entire trial was 0.98 (95% confidence interval: 0.86, 1.10). No reduction in gastrointestinal illness was detected after in-home use of a device designed to be highly effective in removing microorganisms from water

A study of changes in genetic and environmental influences on weight and shape concern across adolescence

The goal of the current study was to examine whether genetic and environmental influences on an important risk factor for disordered eating, weight and shape concern (WSC), remained stable over adolescence. This stability was assessed in two ways: whether new sources of latent variance were introduced over development, and whether the magnitude of variance contributing to the risk factor changed. We examined an 8-item WSC sub-scale derived from the Eating Disorder Examination using telephone interviews with female adolescents. From three waves of data collected from female-female same sex twin pairs from the Australian Twin Registry, a subset of the data (which included 351 pairs at Wave 1) was used to examine three age cohorts: 12-13, 13-15, and 14-16 years. The best fitting model contained genetic and environmental influences, both shared and non-shared. Biometric model fitting indicated that non-shared environmental influences were largely specific to each age cohort, and results suggested that latent shared environmental and genetic influences that were influential at 12-13 years continued to contribute to subsequent age cohorts, with independent sources of both emerging at ages 13-15. The magnitude of all three latent influences could be constrained to be the same across adolescence. Ages 13-15 was indicated as a time of risk for the development of high levels of WSC given that most specific environmental risk factors were significant at this time (e.g., peer teasing about weight, adverse life events), and indications of the emergence of new sources of latent genetic and environmental variance over this period.NHMRC Grants 324715 and 480420

Novel lactoferrin-conjugated gallium complex to treat Pseudomonas aeruginosa wound infection

Pseudomonas aeruginosa is one of the leading causes of opportunistic infections such as chronic wound infection that could lead to multiple organ failure and death. Gallium (Ga3+) ions are known to inhibit P. aeruginosa growth and biofilm formation but require carrier for localized controlled delivery. Lactoferrin (LTf), a two-lobed protein, can deliver Ga3+ at sites of infection. This study aimed to develop a Ga-LTf complex for the treatment of wound infection. The characterisation of the Ga-LTf complex was conducted using differential scanning calorimetry (DSC), Infra-Red (FTIR) and Inductive Coupled Plasma Optical Emission Spectrometry (ICP-OES). The antibacterial activity was assessed by agar disc diffusion, liquid broth and biofilm inhibition assays using the colony forming units (CFUs). The healing capacity and biocompatibility were evaluated using a P.aeruginosa infected wound in a rat model. DSC analyses showed thermal transition consistent with apo-lactoferrin; FTIR confirmed the complexation of gallium to lactoferrin. ICP-OES confirmed the controlled local delivery of Ga3+. Ga-LTf showed a 0.57 log10 CFUs reduction at 24 h compared with untreated control in planktonic liquid broth assay. Ga-LTf showed the highest antibiofilm activity with a 2.24 log10 CFUs reduction at 24 h. Furthermore, Ga-LTf complex is biocompatible without any adverse effect on brain, kidney, liver and spleen of rats tested in this study. Ga-LTf can be potentially promising novel therapeutic agent to treat pathogenic bacterial infections