Integrated regulation of PIKK-mediated stress responses by AAA+ proteins RUVBL1 and RUVBL2

Proteins of the phosphatidylinositol 3-kinase-related protein kinase (PIKK) family are activated by various cellular stresses, including DNA damage, premature termination codon and nutritional status, and induce appropriate cellular responses. The importance of PIKK functions in the maintenance of genome integrity, accurate gene expression and the proper control of cell growth/proliferation is established. Recently, ATPase associated diverse cellular activities (AAA+) proteins RUVBL1 and RUVBL2 (RUVBL1/2) have been shown to be common regulators of PIKKs. The RUVBL1/2 complex regulates PIKK-mediated stress responses through physical interactions with PIKKs and by controlling PIKK mRNA levels. In this review, the functions of PIKKs in stress responses are outlined and the physiological significance of the integrated regulation of PIKKs by the RUVBL1/2 complex is presented. We also discuss a putative “PIKK regulatory chaperone complex” including other PIKK regulators, Hsp90 and the Tel2 complex

A sense of embodiment is reflected in people's signature size

BACKGROUND: The size of a person's signature may reveal implicit information about how the self is perceived although this has not been closely examined. METHODS/RESULTS: We conducted three experiments to test whether increases in signature size can be induced. Specifically, the aim of these experiments was to test whether changes in signature size reflect a person's current implicit sense of embodiment. Experiment 1 showed that an implicit affect task (positive subliminal evaluative conditioning) led to increases in signature size relative to an affectively neutral task, showing that implicit affective cues alter signature size. Experiments 2 and 3 demonstrated increases in signature size following experiential self-focus on sensory and affective stimuli relative to both conceptual self-focus and external (non-self-focus) in both healthy participants and patients with anorexia nervosa, a disorder associated with self-evaluation and a sense of disembodiment. In all three experiments, increases in signature size were unrelated to changes in self-reported mood and larger than manipulation unrelated variations. CONCLUSIONS: Together, these findings suggest that a person's sense of embodiment is reflected in their signature size

Decision-to-incision times and maternal and infant outcomes.

Journal ArticleOBJECTIVE: To measure decision-to-incision intervals and related maternal and neonatal outcomes in a cohort of women undergoing emergency cesarean deliveries at multiple university-based hospitals comprising the National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. METHODS: All women undergoing a primary cesarean delivery at a Network center during a 2-year time span were prospectively ascertained. Emergency procedures were defined as those performed for umbilical cord prolapse, placental abruption, placenta previa with hemorrhage, nonreassuring fetal heart rate pattern, or uterine rupture. Detailed information regarding maternal and neonatal outcomes, including the interval from the decision time to perform cesarean delivery to the actual skin incision, was collected. RESULTS: Of the 11,481 primary cesarean deliveries, 2,808 were performed for an emergency indication. Of these, 1,814 (65%) began within 30 minutes of the decision to operate. Maternal complication rates, including endometritis, wound infection, and operative injury, were not related to the decision-to-incision interval. Measures of newborn compromise including umbilical artery pH less than 7 and intubation in the delivery room were significantly greater when the cesarean delivery was commenced within 30 minutes, likely attesting to the need for expedited delivery. Of the infants with indications for an emergency cesarean delivery who were delivered more than 30 minutes after the decision to operate, 95% did not experience a measure of newborn compromise. CONCLUSION: Approximately one third of primary cesarean deliveries performed for emergency indications are commenced more than 30 minutes after the decision to operate, and the majority were for nonreassuring heart rate tracings. In these cases, adverse neonatal outcomes were not increased. LEVEL OF EVIDENCE: II-2

The differential effects of core stabilization exercise regime and conventional physiotherapy regime on postural control parameters during perturbation in patients with movement and control impairment chronic low back pain

<p>Abstract</p> <p>Background</p> <p>The purpose of the present study was to examine the differential effect of core stability exercise training and conventional physiotherapy regime on altered postural control parameters in patients with chronic low back pain (CLBP). As heterogeneity in CLBP population moderates the effect of intervention on outcomes, in this study, interventions approaches were used based on sub-groups of CLBP.</p> <p>Methods</p> <p>This was an allocation concealed, blinded, sequential and pragmatic control trial. Three groups of participants were investigated during postural perturbations: 1) CLBP patients with movement impairment (n = 15, MI group) randomized to conventional physiotherapy regime 2) fifteen CLBP patients with control impairment randomized to core stability group (CI group) and 3) fifteen healthy controls (HC).</p> <p>Results</p> <p>The MI group did not show any significant changes in postural control parameters after the intervention period however they improved significantly in disability scores and fear avoidance belief questionnaire work score (P < 0.05). The CI group showed significant improvements in Fx, Fz, and My variables (p < 0.013, p < 0.006, and p < 0.002 respectively with larger effect sizes: Hedges's g > 0.8) after 8 weeks of core stability exercises for the adjusted p values. Postural control parameters of HC group were analyzed independently with pre and post postural control parameters of CI and MI group. This revealed the significant improvements in postural control parameters in CI group compared to MI group indicating the specific adaptation to the core stability exercises in CI group. Though the disability scores were reduced significantly in CI and MI groups (p < 0.001), the post intervention scores between groups were not found significant (p < 0.288). Twenty percentage absolute risk reduction in flare-up rates during intervention was found in CI group (95% CI: 0.69-0.98).</p> <p>Conclusions</p> <p>In this study core stability exercise group demonstrated significant improvements after intervention in ground reaction forces (Fz, Mz; g > 0.8) indicating changes in load transfer patterns during perturbation similar to HC group.</p> <p>Trial registration</p> <p>UTRN095032158-06012009423714</p

Captive-bred Atlantic salmon released into the wild have fewer offspring than wild-bred fish and decrease population productivity

The release of captive-bred animals into the wild is commonly practised to restore or supplement wild populations but comes with a suite of ecological and genetic consequences. Vast numbers of hatchery-reared fish are released annually, ostensibly to restore/enhance wild populations or provide greater angling returns. While previous studies have shown that captive-bred fish perform poorly in the wild relative to wild-bred conspecifics, few have measured individual lifetime reproductive success (LRS) and how this affects population productivity. Here, we analyse data on Atlantic salmon from an intensely studied catchment into which varying numbers of captive-bred fish have escaped/been released and potentially bred over several decades. Using a molecular pedigree, we demonstrate that, on average, the LRS of captive-bred individuals was only 36% that of wild-bred individuals. A significant LRS difference remained after excluding individuals that left no surviving offspring, some of which might have simply failed to spawn, consistent with transgenerational effects on offspring survival. The annual productivity of the mixed population (wild-bred plus captive-bred) was lower in years where captive-bred fish comprised a greater fraction of potential spawners. These results bolster previous empirical and theoretical findings that intentional stocking, or non-intentional escapees, threaten, rather than enhance, recipient natural populations

Characteristics of chronic non-specific musculoskeletal pain in children and adolescents attending a rheumatology outpatients clinic: a cross-sectional study

Background: Chronic non-specific musculoskeletal pain (CNSMSP) may develop in childhood and adolescence, leading to disability and reduced quality of life that continues into adulthood. The purpose of the study was to build a biopsychosocial profile of children and adolescents with CNSMSP. Methods: CNSMSP subjects (n = 30, 18 females, age 7-18) were compared with age matched pain free controls across a number of biopsychosocial domains. Results: In the psychosocial domain CNSMSP subjects had increased levels of anxiety and depression, and had more somatic pain complaints. In the lifestyle domain CNSMSP subjects had lower physical activity levels, but no difference in television or computer use compared to pain free subjects. Physically, CNSMSP subjects tended to sit with a more slumped spinal posture, had reduced back muscle endurance, increased presence of joint hypermobility and poorer gross motor skills. Conclusion: These findings support the notion that CNSMSP is a multidimensional biopsychosocial disorder. Further research is needed to increase understanding of how the psychosocial, lifestyle and physical factors develop and interact in CNSMSP

A multicentre evaluation and expert recommendations of use of the newly developed BioFire Joint Infection polymerase chain reaction panel.

Septic arthritis is a serious condition with significant morbidity and mortality, routinely diagnosed using culture. The FDA has recently approved the rapid molecular BioFire® Joint Infection Panel (BJIP) for synovial fluid. We aimed to evaluate the BJIP compared to culture and its potential use in patient management. A multicentre retrospective evaluation of BJIP was conducted in the UK and Ireland. Positive percent agreement (PPA) and negative percent agreement (NPA) were calculated between the BJIP and routine culture. A multidisciplinary team (MDT) discussion addressing the optimal or potential case use of the assay practice was facilitated. Three hundred ninety-nine surplus synovial fluid samples (~ 70% from native joints) from eight centres were processed using BJIP in addition to routine culture. An increased yield of positive results was detected using BJIP compared to routine culture (98 vs 83), giving an overall PPA of 91.6% and overall NPA of 93% for the BJIP compared to culture results. The BJIP detected resistant markers and additional organisms that could influence antibiotic choices including Neisseria gonorrhoeae and Kingella kingae. The MDT agreed that the assay could be used, in addition to standard methods, in adult and children patients with specialist advice use based on local needs. Rapid results from BJIP were assessed as having potential clinical impact on patient management. Organisms not included in the panel may be clinically significant and may limit the value of this test for PJI

Dry weather induces outbreaks of human West Nile virus infections

<p>Abstract</p> <p>Background</p> <p>Since its first occurrence in the New York City area during 1999, West Nile virus (WNV) has spread rapidly across North America and has become a major public health concern in North America. By 2002, WNV was reported in 40 states and the District of Columbia with 4,156 human and 14,539 equine cases of infection. Mississippi had the highest human incidence rate of WNV during the 2002 epidemic in the United States. Epidemics of WNV can impose enormous impacts on local economies. Therefore, it is advantageous to predict human WNV risks for cost-effective controls of the disease and optimal allocations of limited resources. Understanding relationships between precipitation and WNV transmission is crucial for predicting the risk of the human WNV disease outbreaks under predicted global climate change scenarios.</p> <p>Methods</p> <p>We analyzed data on the human WNV incidences in the 82 counties of Mississippi in 2002, using standard morbidity ratio (SMR) and Bayesian hierarchical models, to determine relationships between precipitation and human WNV risks. We also entertained spatial autocorrelations of human WNV risks with conditional autocorrelative (CAR) models, implemented in WinBUGS 1.4.3.</p> <p>Results</p> <p>We observed an inverse relationship between county-level human WNV incidence risk and total annual rainfall during the previous year. Parameters representing spatial heterogeneity in the risk of human exposure to WNV improved model fit. Annual precipitation of the previous year was a predictor of spatial variation of WNV risk.</p> <p>Conclusions</p> <p>Our results have broad implications for risk assessment of WNV and forecasting WNV outbreaks. Assessing risk of vector-born infectious diseases will require understanding of complex ecological relationships. Based on the climatologically characteristic drought occurrence in the past and on climate model predictions for climate change and potentially greater drought occurrence in the future, we suggest that the frequency and relative risk of WNV outbreaks could increase.</p

A candidate probiotic with unfavourable effects in subjects with irritable bowel syndrome: a randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>Some probiotics have shown efficacy for patients with irritable bowel syndrome (IBS). <it>Lactobacillus (L.) plantarum </it>MF1298 was found to have the best <it>in vitro </it>probiotic properties of 22 strains of lactobacilli. The aim of this study was to investigate the symptomatic effect of <it>L. plantarum </it>MF1298 in subjects with IBS. Primary outcome was treatment preference and secondary outcomes were number of weeks with satisfactory relief of symptoms and IBS sum score.</p> <p>Methods</p> <p>The design was a randomised double blind placebo-controlled crossover trial. 16 subjects with IBS underwent two three-week periods of daily intake of one capsule of 10¹⁰CFU <it>L. plantarum </it>MF 1298 or placebo separated by a four-week washout period.</p> <p>Results</p> <p>Thirteen participants (81%; 95% CI 57% to 93%; <it>P </it>= 0.012) preferred placebo to <it>L. plantarum </it>MF1298 treatment. The mean (SD) number of weeks with satisfactory relief of symptoms in the periods with <it>L. plantarum </it>MF1298 and placebo were 0.50 (0.89) and 1.44 (1.26), respectively (<it>P </it>= 0.006). IBS sum score was 6.44 (1.81) in the period with <it>L. plantarum </it>MF1298 treatment compared with 5.35 (1.77) in the period with placebo (<it>P </it>= 0.010). With a clinically significant difference in the IBS sum score of 2 in disfavour of active treatment, the number needed to harm was 3.7, 95% CI 2.3 to 10.9.</p> <p>Conclusions</p> <p>This trial shows for the first time an unfavourable effect on symptoms in subjects with IBS after intake of a potential probiotic.</p> <p>The trial registration number</p> <p>Clinical trials NCT00355810.</p