Wolbachia in the flesh: symbiont intensities in germ-line and somatic tissues challenge the conventional view of Wolbachia transmission routes

Symbionts can substantially affect the evolution and ecology of their hosts. The investigation of the tissue-specific distribution of symbionts (tissue tropism) can provide important insight into host-symbiont interactions. Among other things, it can help to discern the importance of specific transmission routes and potential phenotypic effects. The intracellular bacterial symbiont Wolbachia has been described as the greatest ever panzootic, due to the wide array of arthropods that it infects. Being primarily vertically transmitted, it is expected that the transmission of Wolbachia would be enhanced by focusing infection in the reproductive tissues. In social insect hosts, this tropism would logically extend to reproductive rather than sterile castes, since the latter constitute a dead-end for vertically transmission. Here, we show that Wolbachia are not focused on reproductive tissues of eusocial insects, and that non-reproductive tissues of queens and workers of the ant Acromyrmex echinatior, harbour substantial infections. In particular, the comparatively high intensities of Wolbachia in the haemolymph, fat body, and faeces, suggest potential for horizontal transmission via parasitoids and the faecal-oral route, or a role for Wolbachia modulating the immune response of this host. It may be that somatic tissues and castes are not the evolutionary dead-end for Wolbachia that is commonly thought

Speech Spectrum's Correlation with Speakers' Eysenck Personality Traits

The current study explored the correlation between speakers' Eysenck personality traits and speech spectrum parameters. Forty-six subjects completed the Eysenck Personality Questionnaire. They were instructed to verbally answer the questions shown on a computer screen and their responses were recorded by the computer. Spectrum parameters of /sh/ and /i/ were analyzed by Praat voice software. Formant frequencies of the consonant /sh/ in lying responses were significantly lower than that in truthful responses, whereas no difference existed on the vowel /i/ speech spectrum. The second formant bandwidth of the consonant /sh/ speech spectrum was significantly correlated with the personality traits of Psychoticism, Extraversion, and Neuroticism, and the correlation differed between truthful and lying responses, whereas the first formant frequency of the vowel /i/ speech spectrum was negatively correlated with Neuroticism in both response types. The results suggest that personality characteristics may be conveyed through the human voice, although the extent to which these effects are due to physiological differences in the organs associated with speech or to a general Pygmalion effect is yet unknown

BIM mediates synergistic killing of B-cell acute lymphoblastic leukemia cells by BCL-2 and MEK inhibitors

B-cell acute lymphoblastic leukemia (B-ALL) is an aggressive hematological disease that kills ~50% of adult patients. With the exception of some BCR-ABL1(+) patients who benefit from tyrosine kinase inhibitors, there are no effective targeted therapies for adult B-ALL patients and chemotherapy remains first-line therapy despite adverse side effects and poor efficacy. We show that, although the MEK/ERK pathway is activated in B-ALL cells driven by different oncogenes, MEK inhibition does not suppress B-ALL cell growth. However, MEK inhibition synergized with BCL-2/BCL-XL family inhibitors to suppress proliferation and induce apoptosis in B-ALL cells. We show that this synergism is mediated by the pro-apoptotic factor BIM, which is dephosphorylated as a result of MEK inhibition, allowing it to bind to and neutralize MCL-1, thereby enhancing BCL-2/BCL-XL inhibitor-induced cell death. This cooperative effect is observed in B-ALL cells driven by a range of genetic abnormalities and therefore has significant therapeutic potential

Measuring changes in self-concept: a qualitative evaluation of outcome questionnaires in people having acupuncture for their chronic health problems

BACKGROUND: Changes in self-concept are an important potential outcome for many interventions for people with long-term conditions. This study sought to identify and evaluate outcome questionnaires suitable for quantifying changes in self-concept in people with long-term conditions, in the context of treatment with acupuncture and Chinese medicine. METHODS: A literature search was followed by an evaluation of three questionnaires: The Wellbeing Questionnaire W-BQ12, the Patient Enablement Instrument (PEI), and the Arizona Integrative Outcome Scale (AIOS). A convenience sample of 23 people completed the questionnaires on two occasions and were interviewed about their experience and their questionnaire responses. All acupuncturists were interviewed. RESULTS: Changes in self-concept were common and emerged over time. The three questionnaires had different strengths and weaknesses in relation to measuring changes in self-concept. The generic AIOS had face validity and was sensitive to changes in self-concept over time, but it lacked specificity. The PEI was sensitive and specific in measuring these changes but had lower acceptability. The sensitivity of the W-BQ12 was affected by initial high scores (ceiling effect) and a shorter timescale but was acceptable and is suitable for repeated administration. The PEI and W-BQ12 questionnaires worked well in combination. CONCLUSION: Changes in self-concept are important outcomes of complex interventions for people with long-term illness and their measurement requires carefully evaluated tools and long-term follow-up. The literature review and the analysis of the strengths and weaknesses of the questionnaires is a resource for other researchers. The W-BQ12 and the PEI both proved useful for this population and a larger quantitative study is planned

Evaluation of the brain-penetrant microtubule-stabilizing agent, dictyostatin, in the PS19 tau transgenic mouse model of tauopathy

Neurodegenerative disorders referred to as tauopathies, which includes Alzheimer's disease (AD), are characterized by insoluble deposits of the tau protein within neuron cell bodies and dendritic processes in the brain. Tau is normally associated with microtubules (MTs) in axons, where it provides MT stabilization and may modulate axonal transport. However, tau becomes hyperphosphorylated and dissociates from MTs in tauopathies, with evidence of reduced MT stability and defective axonal transport. This has led to the hypothesis that MT-stabilizing drugs may have potential for the treatment of tauopathies. Prior studies demonstrated that the brain-penetrant MT-stabilizing drug, epothilone D, had salutary effects in transgenic (Tg) mouse models of tauopathy, improving MT density and axonal transport, while reducing axonal dystrophy. Moreover, epothilone D enhanced cognitive performance and decreased hippocampal neuron loss, with evidence of reduced tau pathology. To date, epothilone D has been the only non-peptide small molecule MT-stabilizing agent to be evaluated in Tg tau mice. Herein, we demonstrate the efficacy of another small molecule brain-penetrant MT-stabilizing agent, dictyostatin, in the PS19 tau Tg mouse model. Although dictyostatin was poorly tolerated at once-weekly doses of 1 mg/kg or 0.3 mg/kg, likely due to gastrointestinal (GI) complications, a dictyostatin dose of 0.1 mg/kg was better tolerated, such that the majority of 6-month old PS19 mice, which harbor a moderate level of brain tau pathology, completed a 3-month dosing study without evidence of significant body weight loss. Importantly, as previously observed with epothilone D, the dictyostatin-treated PS19 mice displayed improved MT density and reduced axonal dystrophy, with a reduction of tau pathology and a trend toward increased hippocampal neuron survival relative to vehicle-treated PS19 mice. Thus, despite evidence of dose-limiting peripheral side effects, the observed positive brain outcomes in dictyostatin-treated aged PS19 mice reinforces the concept that MT-stabilizing compounds have significant potential for the treatment of tauopathies

Simultaneous bilateral hip replacement reveals superior outcome and fewer complications than two-stage procedures: a prospective study including 1819 patients and 5801 follow-ups from a total joint replacement registry

<p>Abstract</p> <p>Background</p> <p>Total joint replacements represent a considerable part of day-to-day orthopaedic routine and a substantial proportion of patients undergoing unilateral total hip arthroplasty require a contralateral treatment after the first operation. This report compares complications and functional outcome of simultaneous versus early and delayed two-stage bilateral THA over a five-year follow-up period.</p> <p>Methods</p> <p>The study is a post hoc analysis of prospectively collected data in the framework of the European IDES hip registry. The database query resulted in 1819 patients with 5801 follow-ups treated with bilateral THA between 1965 and 2002. According to the timing of the two operations the sample was divided into three groups: I) 247 patients with simultaneous bilateral THA, II) 737 patients with two-stage bilateral THA within six months, III) 835 patients with two-stage bilateral THA between six months and five years.</p> <p>Results</p> <p>Whereas postoperative hip pain and flexion did not differ between the groups, the best walking capacity was observed in group I and the worst in group III. The rate of intraoperative complications in the first group was comparable to that of the second. The frequency of postoperative local and systemic complication in group I was the lowest of the three groups. The highest rate of complications was observed in group III.</p> <p>Conclusions</p> <p>From the point of view of possible intra- and postoperative complications, one-stage bilateral THA is equally safe or safer than two-stage interventions. Additionally, from an outcome perspective the one-stage procedure can be considered to be advantageous.</p

Excellent Adherence to Antiretrovirals in HIV+ Zambian Children Is Compromised by Disrupted Routine, HIV Nondisclosure, and Paradoxical Income Effects

INTRODUCTION: A better understanding of pediatric antiretroviral therapy (ART) adherence in sub-Saharan Africa is necessary to develop interventions to sustain high levels of adherence. METHODOLOGY/PRINCIPAL FINDINGS: Adherence among 96 HIV-infected Zambian children (median age 6, interquartile range [IQR] 2,9) initiating fixed-dose combination ART was measured prospectively (median 23 months; IQR 20,26) with caregiver report, clinic and unannounced home-based pill counts, and medication event monitoring systems (MEMS). HIV-1 RNA was determined at 48 weeks. Child and caregiver characteristics, socio-demographic status, and treatment-related factors were assessed as predictors of adherence. Median adherence was 97.4% (IQR 96.1,98.4%) by visual analog scale, 94.8% (IQR 86,100%) by caregiver-reported last missed dose, 96.9% (IQR 94.5,98.2%) by clinic pill count, 93.4% (IQR 90.2,96.7%) by unannounced home-based pill count, and 94.8% (IQR 87.8,97.7%) by MEMS. At 48 weeks, 72.6% of children had HIV-1 RNA <50 copies/ml. Agreement among adherence measures was poor; only MEMS was significantly associated with viral suppression (p = 0.013). Predictors of poor adherence included changing residence, school attendance, lack of HIV disclosure to children aged nine to 15 years, and increasing household income. CONCLUSIONS/SIGNIFICANCE: Adherence among children taking fixed-dose combination ART in sub-Saharan Africa is high and sustained over two years. However, certain groups are at risk for treatment failure, including children with disrupted routines, no knowledge of their HIV diagnosis among older children, and relatively high household income, possibly reflecting greater social support in the setting of greater poverty

The Properties of Lion Roars and Electron Dynamics in Mirror Mode Waves Observed by the Magnetospheric MultiScale Mission

Mirror mode waves are ubiquitous in the Earth's magnetosheath, in particular behind the quasi‐perpendicular shock. Embedded in these nonlinear structures, intense lion roars are often observed. Lion roars are characterized by whistler wave packets at a frequency ∼100 Hz, which are thought to be generated in the magnetic field minima. In this study, we make use of the high time resolution instruments on board the Magnetospheric MultiScale mission to investigate these waves and the associated electron dynamics in the quasi‐perpendicular magnetosheath on 22 January 2016. We show that despite a core electron parallel anisotropy, lion roars can be generated locally in the range 0.05–0.2fce by the perpendicular anisotropy of electrons in a particular energy range. We also show that intense lion roars can be observed up to higher frequencies due to the sharp nonlinear peaks of the signal, which appear as sharp spikes in the dynamic spectra. As a result, a high sampling rate is needed to estimate correctly their amplitude, and the latter might have been underestimated in previous studies using lower time resolution instruments. We also present for the first‐time 3‐D high time resolution electron velocity distribution functions in mirror modes. We demonstrate that the dynamics of electrons trapped in the mirror mode structures are consistent with the Kivelson and Southwood (1996) model. However, these electrons can also interact with the embedded lion roars: first signatures of electron quasi‐linear pitch angle diffusion and possible signatures of nonlinear interaction with high‐amplitude wave packets are presented. These processes can lead to electron untrapping from mirror modes

Pulmonary arterial medial smooth muscle thickness in sudden infant death syndrome: an analysis of subsets of 73 cases

Previous studies addressing pulmonary artery morphology have compared cases of sudden infant death syndrome (SIDS) to controls but none have compared demographic profiles, exposure to potentially hypoxic risk factors and other pathologic variables in SIDS cases grouped according to pulmonary artery medial smooth muscle thickness. Aims: To compare the relative medial thickness (RMT) in alveolar wall arteries (AW) in SIDS cases with that in age-matched controls and 2. Compare demographic, clinical, and pathologic characteristics among three subsets of SIDS cases based upon alveolar wall (AW) RMT. Retrospective morphometric planimetry of all muscularized arteries in standardized right apical lung sections in 73 SIDS cases divided into three groups based on increasing AW RMT as well as 19 controls age-matched to 19 of the SIDS cases. SIDS and age-matched control cases did not differ with respect to AW RMT or other demographic variables. The SIDS group with the thickest AW RMT had significantly more males and premature birth than the other groups, but the groups did not differ for known clinical risk factors that would potentially expose them to hypoxia. Pathologic variables, including pulmonary inflammation, gastric aspiration, intra-alveolar siderophages, cardiac valve circumferences, and heart and liver weights, were not different between groups. Age was not significantly correlated with RMT of alveolar wall and pre-acinar arteries but was significant at p = .018 for small intra-acinar arteries. The groups were different for RMT of small pre-acinar and intra-acinar arteries, which increased with increasing AW RMT. Statistical differences should not necessarily be equated with clinical importance, however future research incorporating more quantified historical data is recommended

Quantifying Age-Related Differences in Information Processing Behaviors When Viewing Prescription Drug Labels

Adverse drug events (ADEs) are a significant problem in health care. While effective warnings have the potential to reduce the prevalence of ADEs, little is known about how patients access and use prescription labeling. We investigated the effectiveness of prescription warning labels (PWLs, small, colorful stickers applied at the pharmacy) in conveying warning information to two groups of patients (young adults and those 50+). We evaluated the early stages of information processing by tracking eye movements while participants interacted with prescription vials that had PWLs affixed to them. We later tested participants’ recognition memory for the PWLs. During viewing, participants often failed to attend to the PWLs; this effect was more pronounced for older than younger participants. Older participants also performed worse on the subsequent memory test. However, when memory performance was conditionalized on whether or not the participant had fixated the PWL, these age-related differences in memory were no longer significant, suggesting that the difference in memory performance between groups was attributable to differences in attention rather than differences in memory encoding or recall. This is important because older adults are recognized to be at greater risk for ADEs. These data provide a compelling case that understanding consumers’ attentive behavior is crucial to developing an effective labeling standard for prescription drugs