Fitness effects of new mutations in Chlamydomonas reinhardtii across two stress gradients

Most spontaneous mutations affecting fitness are likely to be deleterious, but the strength of selection acting on them might be impacted by environmental stress. Such stress‐dependent selection could expose hidden genetic variation, which in turn might increase the adaptive potential of stressed populations. On the other hand, this variation might represent a genetic load and thus lead to population extinction under stress. Previous studies to determine the link between stress and mutational effects on fitness, however, have produced inconsistent results. Here, we determined the net change in fitness in 29 genotypes of the green algae Chlamydomonas reinhardtii that accumulated mutations in the near absence of selection for approximately 1000 generations across two stress gradients, increasing NaCl and decreasing phosphate. We found mutational effects to be magnified under extremely stressful conditions, but such effects were specific both to the type of stress and to the genetic background. The detection of stress‐dependent fitness effects of mutations depended on accurately scaling relative fitness measures by generation times, thus offering an explanation for the inconsistencies among previous studies

An evaluation of the effectiveness of PROMPT therapy in improving speech production accuracy in six children with cerebral palsy

This study evaluates perceptual changes in speech production accuracy in six children (3 – 11 years) with moderate-to-severe speech impairment associated with cerebral palsy before, during, and after participation in a motor-speech intervention program (Prompts for Restructuring Oral Muscular Phonetic Targets). An A1BCA2 single subject research design was implemented. Subsequent to the baseline phase (phase A1), phase B targeted each participant’s first intervention priority on the PROMPT motor-speech hierarchy. Phase C then targeted one level higher. Weekly speech probes were administered, containing trained and untrained words at the two levels of intervention, plus an additional level that served as a control goal. The speech probes were analysed for motor-speech-movement-parameters and perceptual accuracy. Analysis of the speech probe data showed all participants recorded a statistically significant change. Between phases A1 – B and B – C 6/6 and 4/6participants, respectively, recorded a statistically significant increase in performance level on the motor speech movement patterns targeted during the training of that intervention. The preliminary data presented in this study make a contribution to providing evidence that supports the use of a treatment approach aligned with dynamic systems theory to improve the motor-speech movement patterns and speech production accuracy in children with cerebral palsy

Poly-substance use and antisocial personality traits at admission predict cumulative retention in a buprenorphine programme with mandatory work and high compliance profile

Background: Continuous abstinence and retention in treatment for alcohol and drug use disorders are central challenges for the treatment providers. The literature has failed to show consistent, strong predictors of retention. Predictors and treatment structure may differ across treatment modalities. In this study the structure was reinforced by the addition of supervised urine samples three times a week and mandatory daily work/structured education activities as a prerequisite of inclusion in the program. Methods: Of 128 patients consecutively admitted to buprenorphine maintenance treatment five patients dropped out within the first week. Of the remaining 123 demographic data and psychiatric assessment were used to predict involuntary discharge from treatment and corresponding cumulative abstinence probability. All subjects were administered the Structured Clinical Interview for DSM-IV-TR, and the Symptom Checklist 90 (SCL-90), the Alcohol Use Disorder Identification Test (AUDIT), the Swedish universities Scales of Personality (SSP) and the Sense of Coherence Scale (SOC), all self-report measures. Some measures were repeated every third month in addition to interviews. Results: Of 123 patients admitted, 86 (70%) remained in treatment after six months and 61 (50%) remained in treatment after 12 months. Of those discharged involuntarily, 34/62 individuals were readmitted after a suspension period of three months. Younger age at intake, poly-substance abuse at intake (number of drugs in urine), and number of conduct disorder criteria on the SCID Screen were independently associated with an increased risk of involuntary discharge. There were no significant differences between dropouts and completers on SCL-90, SSP, SOC or AUDIT. Conclusion: Of the patients admitted to the programme 50% stayed for the first 12 months with continuous abstinence and daily work. Poly-substance use before intake into treatment, high levels of conduct disorder on SCID screen and younger age at intake had a negative impact on retention and abstinence

Polypharmacy among anabolic-androgenic steroid users: A descriptive metasynthesis

Background: As far as we are aware, no previous systematic review and synthesis of the qualitative/descriptive literature on polypharmacy in anabolic-androgenic steroid(s) (AAS) users has been published. Method: We systematically reviewed and synthesized qualitative/descriptive literature gathered from searches in electronic databases and by inspecting reference lists of relevant literature to investigate AAS users' polypharmacy. We adhered to the recommendations of the UK Economic and Social Research Council's qualitative research synthesis manual and the PRISMA guidelines. Results: A total of 50 studies published between 1985 and 2014 were included in the analysis. Studies originated from 10 countries although most originated from United States (n = 22), followed by Sweden (n = 7), England only (n = 5), and the United Kingdom (n = 4). It was evident that prior to their debut, AAS users often used other licit and illicit substances. The main ancillary/supplementary substances used were alcohol, and cannabis/cannabinoids followed by cocaine, growth hormone, and human chorionic gonadotropin (hCG), amphetamine/meth, clenbuterol, ephedra/ephedrine, insulin, and thyroxine. Other popular substance classes were analgesics/opioids, dietary/nutritional supplements, and diuretics. Our classification of the various substances used by AAS users resulted in 13 main groups. These non-AAS substances were used mainly to enhance the effects of AAS, combat the side effects of AAS, and for recreational or relaxation purposes, as well as sexual enhancement. Conclusions: Our findings corroborate previous suggestions of associations between AAS use and the use of other licit and illicit substances. Efforts must be intensified to combat the debilitating effects of AAS-associated polypharmacy

Effect of a myosin regulatory light chain mutation K104E on actin-myosin interactions

Familial hypertrophic cardiomyopathy (FHC) is the most common cause of sudden cardiac death in young individuals. Molecular mechanisms underlying this disorder are largely unknown; this study aims at revealing how disruptions in actin-myosin interactions can play a role in this disorder. Cross-bridge (XB) kinetics and the degree of order were examined in contracting myofibrils from the ex vivo left ventricles of transgenic (Tg) mice expressing FHC regulatory light chain (RLC) mutation K104E. Because the degree of order and the kinetics are best studied when an individual XB makes a significant contribution to the overall signal, the number of observed XBs in an ex vivo ventricle was minimized to ∼20. Autofluorescence and photobleaching were minimized by labeling the myosin lever arm with a relatively long-lived red-emitting dye containing a chromophore system encapsulated in a cyclic macromolecule. Mutated XBs were significantly better ordered during steady-state contraction and during rigor, but the mutation had no effect on the degree of order in relaxed myofibrils. The K104E mutation increased the rate of XB binding to thin filaments and the rate of execution of the power stroke. The stopped-flow experiments revealed a significantly faster observed dissociation rate in Tg-K104E vs. Tg-wild-type (WT) myosin and a smaller second-order ATP-binding rate for the K104E compared with WT myosin. Collectively, our data indicate that the mutation-induced changes in the interaction of myosin with actin during the contraction-relaxation cycle may contribute to altered contractility and the development of FHC