Diet adaptation in dog reflects spread of prehistoric agriculture.

Adaptations allowing dogs to thrive on a diet rich in starch, including a significant AMY2B copy number gain, constituted a crucial step in the evolution of the dog from the wolf. It is however not clear whether this change was associated with the initial domestication, or represents a secondary shift related to the subsequent development of agriculture. Previous efforts to study this process were based on geographically limited data sets and low-resolution methods, and it is therefore not known to what extent the diet adaptations are universal among dogs and whether there are regional differences associated with alternative human subsistence strategies. Here we use droplet PCR to investigate worldwide AMY2B copy number diversity among indigenous as well as breed dogs and wolves to elucidate how a change in dog diet was associated with the domestication process and subsequent shifts in human subsistence. We find that AMY2B copy numbers are bimodally distributed with high copy numbers (median 2nAMY2B=11) in a majority of dogs but no, or few, duplications (median 2nAMY2B=3) in a small group of dogs originating mostly in Australia and the Arctic. We show that this pattern correlates geographically to the spread of prehistoric agriculture and conclude that the diet change may not have been associated with initial domestication but rather the subsequent development and spread of agriculture to most, but not all regions of the globe.

Gender differences in cadmium and cotinine levels in prepubertal children.

Susceptibility to environmental stressors has been described for fetal and early childhood development. However, the possible susceptibility of the prepubertal period, characterized by the orchestration of the organism towards sexual maturation and adulthood has been poorly investigated and exposure data are scarce. In the current study levels of cadmium (Cd), cotinine and creatinine in urine were analyzed in a subsample 216 children from 12 European countries within the DEMOCOPHES project. The children were divided into six age-sex groups: boys (6-8 years, 9-10 years and 11 years old), and girls (6-7 years, 8-9 years, 10-11 years). The number of subjects per group was between 23 and 53. The cut off values were set at 0.1 µg/L for Cd, and 0.8 µg/L for cotinine defined according to the highest limit of quantification. The levels of Cd and cotinine were adjusted for creatinine level. In the total subsample group, the median level of Cd was 0.180 µg/L (range 0.10-0.69 µg/L), and for cotinine the median wet weight value was 1.50 µg/L (range 0.80-39.91 µg/L). There was no significant difference in creatinine and cotinine levels between genders and age groups. There was a significant correlation between levels of cadmium and creatinine in all children of both genders. This shows that even at such low levels the possible effect of cadmium on kidney function was present and measurable. An increase in Cd levels was evident with age. Cadmium levels were significantly different between 6-7 year old girls, 11 year old boys and 10-11 year old girls. As there was a balanced distribution in the number of subjects from countries included in the study, bias due to data clustering was not probable. The impact of low Cd levels on kidney function and gender differences in Cd levels needs further investigation.

Specialized psychosocial treatment plus treatment as usual (TAU) versus TAU for patients with cannabis use disorder and psychosis: the CapOpus randomized trial.

BACKGROUND: Cannabis abuse in psychotic patients is associated with rehospitalizations, reduced adherence and increased symptom severity. Previous psychosocial interventions have been ineffective in cannabis use, possibly because of low sample sizes and short interventions. We investigated whether adding CapOpus to treatment as usual (TAU) reduces cannabis use in patients with cannabis use disorder and psychosis. Method A total of 103 patients with psychosis and cannabis use disorder were centrally randomized to 6 months of CapOpus plus TAU (n = 52) or TAU (n = 51). CapOpus consisted mainly of motivational interviewing and cognitive behaviour therapy (CBT). TAU was targeted primarily at the psychotic disorder. The primary outcome was self-reported days with cannabis use in the preceding month. RESULTS: Pre-randomization cannabis use frequency was 14.9 [95% confidence interval (CI) 12.7-17.1] days/month. Post-treatment, the ratio of days/month with cannabis use in CapOpus versus TAU was 0.76 (95% CI 0.38-1.50) (p = 0.42), and 0.80 (95% CI 0.21-3.10) (p = 0.75) at the 4-month follow-up. From 46.4 (95% CI 36.4-56.3) monthly joints pre-randomization, consumption fell to 27.3 (95% CI 12.6-41.9) joints in CapOpus and 48.2 (95% CI 31.8-64.6) in TAU (p = 0.06). Follow-up amounts were 28.4 (95% CI 13.5-43.2) and 41.6 (95% CI 25.2-58.0) joints (p = 0.23). Several subgroup analyses suggested benefits of CapOpus. CONCLUSIONS: CapOpus did not reduce the frequency, but possibly the amount, of cannabis use. This is similar to the findings of previous trials in this population. Implementation of CapOpus-type interventions is thus not warranted at present but subgroup analyses call for further trials.

Mindfulness-based stress reduction and mindfulness-based cognitive therapy: a systematic review of randomized controlled trials.

UNLABELLED: Fjorback LO, Arendt M, Ørnbøl E, Fink P, Walach H. Mindfulness-Based Stress Reduction and Mindfulness-Based Cognitive Therapy - a systematic review of randomized controlled trials. OBJECTIVE: To systematically review the evidence for MBSR and MBCT. METHOD: Systematic searches of Medline, PsycInfo and Embase were performed in October 2010. MBSR, MBCT and Mindfulness Meditation were key words. Only randomized controlled trials (RCT) using the standard MBSR/MBCT programme with a minimum of 33 participants were included. RESULTS: The search produced 72 articles, of which 21 were included. MBSR improved mental health in 11 studies compared to wait list control or treatment as usual (TAU) and was as efficacious as active control group in three studies. MBCT reduced the risk of depressive relapse in two studies compared to TAU and was equally efficacious to TAU or an active control group in two studies. Overall, studies showed medium effect sizes. Among other limitations are lack of active control group and long-term follow-up in several studies. CONCLUSION: Evidence supports that MBSR improves mental health and MBCT prevents depressive relapse. Future RCTs should apply optimal design including active treatment for comparison, properly trained instructors and at least one-year follow-up. Future research should primarily tackle the question of whether mindfulness itself is a decisive ingredient by controlling against other active control conditions or true treatments.

The human and canine TERT promoters function equivalently in human and canine cells.

Telomerase targeted cancer gene therapy is being exploited for treatment of human cancer. The high incidence and many comparative aspects of human and canine cancer and the compliance and dedication of dog owners to treat cancer makes the canine pet population a good clinical model for investigating and developing new cancer therapeutics. Here, we report that the human telomerase promoter operates in canine cells, suggesting that human telomerase promoter-driven cancer therapy can be used to treat cancer in canines. Therefore, the canine pet population can act as a clinical model for new drug development based on telomerase therapeutics.

Oncolytic gene therapy for canine cancers: teaching old dog viruses new tricks.

The use of viruses to treat cancer has been studied for decades. With the advancement of molecular biology, viruses have been modified and genetically engineered to optimize their ability to target cancer cells. Canine viruses, such as distemper virus and adenovirus, are being exploited for the treatment of canine cancer as the dog has proven to be a good comparative model for human cancer research and proof of concept investigations. In this review, we introduce the concept of oncolytic viruses and describe some of the preliminary attempts to use oncolytic viruses for the treatment of canine cancer.

A randomized study of massed three-week cognitive behavioural therapy schedule for panic disorder.

OBJECTIVE: To compare the efficacy of massed vs. spaced group cognitive behavioural therapy (CBT) for patients with panic disorder with or without agoraphobia (PD). METHOD: Thirty-nine PD patients were randomly assigned to massed group CBT (daily 4-h sessions in week 1, two 2-h sessions in week 2 and one 2-h session in week 3) or traditional spaced weekly group CBT (13 consecutive, weekly 2-h sessions). The content and number of hours in the two treatment schedules were identical. Outcome was assessed after treatment, and at 3, 6 and 18 months of follow-up. RESULTS: Both treatment groups achieved significant improvement on all measures with large pre- to post-treatment and pre-treatment to follow-up effect sizes. No between-group differences were registered. Adherence and patient satisfaction did not differ between groups. CONCLUSION: The massed, 3-week group CBT schedule proved to be effective and feasible for PD patients with outcomes comparable with that of standard, spaced group CBT.

Multipoint recognition of basic proteins at a membrane model.

Cell surface recognition achieves high efficiency and specificity because of its polyvalent nature. A biomimetic model has been designed, which consists of a stearic acid monolayer with embedded calixarene tetraphosphonate receptor molecules. This system is able to distinguish between proteins of varying pI at nanomolar concentrations.

Optimization of a synthetic arginine receptor. Systematic tuning of noncovalent interactions.

The simple arginine binder 1 could be optimized by strengthening pi-cation as well as electrostatic interactions. Electron-donating or -withdrawing substituents in the 5-position provide experimental evidence for pi-cation interactions, because binding energies increase by up to 0.6 kcal/mol due to a single benzene-guanidinium interaction. Even more effective is the introduction of a third phosphonate functionality at the correct distance, so that the guanidinium cation is recognized by optimal electrostatic and hydrogen bond interactions. Monte Carlo simulations and NOESY experiments confirm the expected complex geometries. The optimized host molecule 8 binds arginine half an order of magnitude more efficiently than the parent molecule.

Effectiveness of psychological debriefing.

OBJECTIVE: To identify literature concerning the effectiveness of psychological debriefing (PD) and analyse results according to different criteria of success and different uses of the intervention format. METHOD: Literature search was made in databases PubMed, PsycInfo and Psychlit. Twenty-five studies were selected for a thorough description. Forty-two studies provided additional information. RESULTS: Results indicate that, in general, debriefing does not prevent psychiatric disorders or mitigate the effects of traumatic stress, even though people generally find the intervention helpful in the process of recovering from traumatic stress. The intervention holds potential as a screening procedure, and there may be economic arguments for continued use. When used with adherence to traditional descriptions of treatment group, events, group format, leadership and time spent, a preventive effect emerges. No tendency according to timing was found. CONCLUSION: Current uses of PD are problematic. The concept needs to be redefined, and the scope of application must be revised. The objectives for use need to be clarified.

Impact of aorto-coronary graft markers on subsequent graft patency: a retrospective review.

The use of aorto-coronary graft markers has not been standard, presumably due to concern about possible adverse effects on subsequent graft patency. Our goal was to determine if there was any increased risk of graft occlusion in patients who received circumferential graft markers at the time of their coronary artery bypass (CAB) surgery. A retrospective review of angiograms was performed for patients with prior CAB. Cohorts with and without graft markers were compared. A total of 405 "unmarked" and 311 "marked" grafts were identified in 335 patients meeting inclusion criteria. Patency is reported in divisions of elapsed time since CAB. Overall patency in the "marked" group (71.1%) was significantly higher than in the "unmarked" group (58.0%, P < 0.001). In this retrospective population, there was no increased risk of graft occlusion in patients who received circumferential graft markers at the time of CAB surgery as compared to those patients who did not.

Internal forces and moments in transpedicular spine instrumentation. The effect of pedicle screw angle and transfixation--the 4R-4bar linkage concept.

The three-dimensional components of force and moment within the plates and screws of a bilevel transpedicular spine implant construct subjected to different physiological loads were determined by experimental and finite element methods. The effect of pedicle screw angle and transfixation were studied. Untransfixed 0 degrees pedicle-to-pedicle (P-P) angle constructs with limited screw-bone torsional resistance are unstable 4R-4bar linkages. They will not resist lateral load or (when not in a rectangular position) axial load until the spinal column load shares. Untransfixed constructs with (0 degrees less than P-P angle less than 60 degrees) are structures. However, as P-P angle approaches 0 degrees, the structure becomes more flexible (unstable) and some internal force and moment components exponentially increase (starting at approximately a 30 degrees P-P angle). Transfixation eliminated the linkage instability and associated exponential increase in internal loads. These observations apply to all bilevel systems that allow no relative joint motion between pedicle screw and longitudinal member. If relative motion does exist, other types of linkage instability can occur.

A modular spinal rod linkage system to provide rotational stability.

The effect of cross linkage on the in vitro stability of paired Harrington distraction rods was studied in an unstable fracture model using calf spine segments. Cross linkage used in conjunction with sublaminar wires significantly improved torsional stability, improved lateral bending stability, and had no adverse affect on stability for axial, forward flexion, or extension loading compared to rods alone, rods with bridges, and wired rods.

In vitro stimulation of T-cell rosette formation by antiserum to thymus factor in Hodgkin's disease.

Patients with Hodgkin's disease manifest decreased percentage of E rosette-forming (T) lymphocytes in the peripheral blood. We have investigated thymosine-like factor in peripheral blood lymphocytes in these patients by immunofluorescence method. Some of lymphocytes showed the excess of thymosine-like factor. The addition of antiserum to thymus factor increased percentage of E rosette-forming (T) lymphocytes in the peripheral blood in Hodgkin's disease.