Clinical Correlates of Social Affect in Early Infancy: Implications for Early Identification of Autism Spectrum Disorder

Earlier intervention for infants and toddlers with autism spectrum disorder (ASD) enhances developmental gains (Rogers, et al. 2012) and necessitates ascertainment of early, reliable indicators of ASD. Diminished social attention and positive social affect have been among the leading hypothesized risk factors for ASD in the prelinguistic period, between 6-12 months of age, however research has resulted in mixed findings for the predictive value of social engagement in 6-9-month-old infants for the development of ASD. If abnormalities in infant social affect contribute to the early phenotypic expression of ASD, it is important to determine whether diminished social affect is a unique construct associated exclusively with social impairments or if it is, alternatively, an expression of normal variation in individual development better explained by temperamental style. The current study sought to enhance the understanding of social development in early infancy by investigating individual differences in social engagement during face-to-face dyadic interactions. Expression of positive social affect during a structured dyadic parent-infant interaction was measured for 33 typically developing 6-8-month old infants. This measure was then correlated with concurrent clinical measures of social-communication, vocal production, autism symptomology, and temperament. Results revealed a positive association between positive social affect and the receptive language component of social-communication. No significant relations were observed between positive social affect, vocal production, autism symptomology, or temperament. These results suggest that infant positive social during interaction with a caregiver is a reflection of some elements of social-communicative ability for 6-8 month old infants, but not temperamental style. Further research is needed to understand how diminished positive social affect in early infancy may impact later developmental outcomes. Implications for early identification of ASD and relevant intervention strategies are discussed

Meiotic drive adaptive testes enlargement during early development in the stalk-eyed fly

The sex ratio (SR) X-linked meiotic drive system in stalk-eyed flies destroys Y-bearing sperm. Unlike other SR systems, drive males do not suffer fertility loss. They have greatly enlarged testes which compensate for gamete killing. We predicted that enlarged testes arise from extended development with resources re-allocated from the accessory glands, as these tend to be smaller in drive males. To test this, we tracked the growth of the testes and accessory glands of wild-type and drive males over 5–6 weeks post-eclosion before males attained sexual maturity. Neither of the original predictions is supported by these data. Instead, we found that the drive male testes were enlarged at eclosion, reflecting a greater allocation of resources to the testes during pupation. Testes grow at a higher rate during early adult development in drive males, but there was no evidence that this retards the growth of the accessory glands. Further experiments are proposed to investigate whether smaller accessory glands only arise in drive males post-copulation or when flies are subjected to nutritional stress. Our experimental findings support the idea that enlarged testes in drive males arise as an adaptive allocation of resources to traits that enhance male reproductive success

Active Shooter Preparedness Among Dental Hygiene Students

Purpose: Active shooter incidents (ASIs) occurring in dental hygiene academic settings present unique challenges and research examining institutional preparation of dental hygiene students for such incidents is lacking. The purpose of this pilot project was to examine the perceived preparedness, confidence, and awareness of dental hygiene students regarding ASIs. Methods: A validated 24-item electronic survey was distributed to dental hygiene students (n=68) at one institution to measure their preparedness, confidence, and awareness regarding ASIs. Descriptive statistics and Pearson correlations were used for data analysis. Results: Fifty-seven dental hygiene students completed the survey for a response rate of 84%. Many participants felt slightly prepared (n=26, 45.6%) or not prepared (n=15, 26.3%) to respond to an ASI in the classroom. Most were slightly confident (n=26, 45.6%) or not confident (n=16, 26.3%) in helping to control the classroom during an ASI. Over half (n=32, 56.1%) were not certain if their institution provided active shooter trainings and were not certain if drills occurred (n=25,43.8%). Perceived preparedness was positively correlated with confidence in helping to control an ASI in the classroom (r(56)=.616, p=.000). Positive correlations were also identified with perceived preparedness to respond in a lab or clinic with the assumption that ASIs are taken seriously at their institution (r(56)=.375, p=.004). Conclusion: A general lack of preparedness and confidence for responding to ASIs may exist among dental hygiene students along with a lack of awareness regarding trainings and drills. Educational institutions should implement best practices for preparing dental hygiene students for ASIs

Mucosal Infections and Invasive Potential of Nonencapsulated <i>Streptococcus pneumoniae</i> Are Enhanced by Oligopeptide Binding Proteins AliC and AliD.

Nonencapsulated &lt;i&gt;Streptococcus pneumoniae&lt;/i&gt; (NESp) is an emerging human pathogen that colonizes the nasopharynx and is associated with noninvasive diseases such as otitis media (OM), conjunctivitis, and nonbacteremic pneumonia. Since capsule expression was previously thought to be necessary for establishment of invasive pneumococcal disease (IPD), serotype-specific polysaccharide capsules are targeted by currently licensed pneumococcal vaccines. Yet, NESp expressing oligopeptide binding proteins AliC and AliD have been isolated during IPD. Thus, we hypothesize AliC and AliD are major NESp virulence determinants that facilitate persistence and development of IPD. Our study reveals that NESp expressing AliC and AliD have intensified virulence compared to isogenic mutants. Specifically, we demonstrate AliC and AliD enhance murine nasopharyngeal colonization and pulmonary infection and are required for OM in a chinchilla model. Furthermore, AliC and AliD increase pneumococcal survival in chinchilla whole blood and aid in resistance to killing by human leukocytes. Comparative proteome analysis revealed significant alterations in protein levels when AliC and AliD were absent. Virulence-associated proteins, including a pneumococcal surface protein C variant (CbpAC), were significantly downregulated, while starvation response indicators were upregulated in the double mutant relative to wild-type levels. We also reveal that differentially expressed CbpAC was essential for NESp adherence to epithelial cells, virulence during OM, reduction of C3b deposition on the NESp surface, and binding to nonspecific IgA. Altogether, the rise in NESp prevalence urges the need to understand how NESp establishes disease and persists in a host. This study highlights the roles of AliC, AliD, and CbpAC in the pathogenesis of NESp. &lt;b&gt;IMPORTANCE&lt;/b&gt; Despite the effective, widespread use of licensed pneumococcal vaccines over many decades, pneumococcal infections remain a worldwide burden resulting in high morbidity and mortality. NESp subpopulations are rapidly rising in the wake of capsule-targeted vaccine strategies, yet there is very little knowledge on NESp pathogenic potential and virulence mechanisms. Although NESp lacks a protective capsule, NESp lineages expressing AliC and AliD have been associated with systemic infections. Furthermore, higher antibiotic resistance rates and transformation efficiencies associated with emerging NESp threaten treatment strategies needed to control pneumococcal infections and transmission. Elucidating how NESp survives within a host and establishes disease is necessary for development of broadened pneumococcal prevention methods. Our study identifies virulence determinants and host survival mechanisms employed by NESp with a high pathogenic potential. Moreover, our study also identifies virulence determinants shared by NESp and encapsulated strains that may serve as broad prevention and therapeutic targets

Surface proteins and pneumolysin of encapsulated and nonencapsulated Streptococcus pneumoniae mediate virulence in a chinchilla model of otitis media

Streptococcus pneumoniae infections result in a range of human diseases and are responsible for almost one million deaths annually. Pneumococcal disease is mediated in part through surface structures and an anti-phagocytic capsule. Recent studies have shown that nonencapsulated Streptococcus pneumoniae (NESp) make up a significant portion of the pneumococcal population and are able to cause disease. NESp lack some common surface proteins expressed by encapsulated pneumococci, but express surface proteins unique to NESp. A chinchilla model of otitis media (OM) was used to determine the effect various pneumococcal mutations have on pathogenesis in both NESp and encapsulated pneumococci. Epithelial cell adhesion and invasion assays were used to examine the effects in relation to deletion of intrinsic genes or expression of novel genes. A mouse model of colonization was also utilized for comparison of various pneumococcal mutants. It was determined that pneumococcal surface protein K (PspK) and pneumolysin (Ply) affect NESp middle ear pathogenesis, but only PspK affected epithelial cell adhesion. Experiments in an OM model were done with encapsulated strains testing the importance of native virulence factors and treatment of OM. First, a triple deletion of the common virulence factors PspA, PspC, and Ply, (ΔPAC), from an encapsulated background abolished virulence in an OM model while a PspC mutant had detectable, but reduced amounts of recoverable bacteria compared to wildtype. Next, treatment of OM was effective when starting antibiotic treatment within 24 hrs with resolution by 48 hrs post treatment. Expression of NESp-specific virulence factor PspK in an encapsulated strain has not been previously studied, and we showed significantly increased adhesion and invasion of human epithelial cells by pneumococci. Murine colonization was not significantly increased when an encapsulated strain expressed PspK, but colonization was increased when a capsule mutant expressed PspK. The ability of PspK expression to increase colonization in a capsule mutant despite no increase in adhesion can be attributed to other functions of PspK, such as sIgA binding or immune modulation. OM is a substantial economic burden, thus a better understanding of both encapsulated pneumococcal pathogenesis and the emerging pathogen NESp is necessary for effective prevention and treatment

Synergistic roles of climate warming and human occupation in Patagonian megafaunal extinctions during the Last Deglaciation

The causes of Late Pleistocene megafaunal extinctions (60,000 to 11,650 years ago, hereafter 60 to 11.65 ka) remain contentious, with major phases coinciding with both human arrival and climate change around the world. The Americas provide a unique opportunity to disentangle these factors as human colonization took place over a narrow time frame (~15 to 14.6 ka) but during contrasting temperature trends across each continent. Unfortunately, limited data sets in South America have so far precluded detailed comparison. We analyze genetic and radiocarbon data from 89 and 71 Patagonian megafaunal bones, respectively, more than doubling the high-quality Pleistocene megafaunal radiocarbon data sets from the region.We identify a narrowmegafaunal extinction phase 12,280 ± 110 years ago, some 1 to 3 thousand years after initial human presence in the area. Although humans arrived immediately prior to a cold phase, the Antarctic Cold Reversal stadial, megafaunal extinctions did not occur until the stadial finished and the subsequent warming phase commenced some 1 to 3 thousand years later. The increased resolution provided by the Patagonian material reveals that the sequence of climate and extinction events in North and South America were temporally inverted, but in both cases, megafaunal extinctions did not occur until human presence and climate warming coincided. Overall, metapopulation processes involving subpopulation connectivity on a continental scale appear to have been critical for megafaunal species survival of both climate change and human impacts.Fil: Metcalf, Jessica L.. University of Adelaide; Australia. State University of Colorado Boulder; Estados UnidosFil: Turney, Chris. University of New South Wales; AustraliaFil: Barnett, Ross. University of Oxford; Reino Unido. Universidad de Copenhagen; DinamarcaFil: Martin, Fabiana. Universidad de Magallanes. Instituto de la Patagonia. Centro de Estudios del Hombre Austral; ChileFil: Bray, Sarah C.. University of Adelaide; Australia. University of South Australia; AustraliaFil: Vilstrup, Julia T.. Universidad de Copenhagen; DinamarcaFil: Orlando, Ludovic. Universidad de Copenhagen; DinamarcaFil: Salas-Gismondi, Rodolfo. Université de Montpellier. Institut des Sciences de l’Evolution; Francia. Universidad Nacional Mayor de San Marcos; PerúFil: Loponte, Daniel Marcelo. Secretaría de Cultura de la Nación. Dirección Nacional de Cultura y Museos. Instituto Nacional de Antropología y Pensamiento Latinoamericano; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Medina, Matias Eduardo. Centro de Estudios Históricos ; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: de Nigris, Mariana Eleonor. Secretaría de Cultura de la Nación. Dirección Nacional de Cultura y Museos. Instituto Nacional de Antropología y Pensamiento Latinoamericano; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Civalero, Maria Teresa. Secretaría de Cultura de la Nación. Dirección Nacional de Cultura y Museos. Instituto Nacional de Antropología y Pensamiento Latinoamericano; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Fernández, Pablo Marcelo. Secretaría de Cultura de la Nación. Dirección Nacional de Cultura y Museos. Instituto Nacional de Antropología y Pensamiento Latinoamericano; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Gasco, Alejandra Valeria. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Exactas y Naturales. Laboratorio de Paleoecología Humana; ArgentinaFil: Duran, Victor Alberto. Universidad Nacional de Cuyo. Facultad de Ciencias Exactas y Naturales. Laboratorio de Paleoecología Humana; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Seymour, Kevin L.. Royal Ontario Museum. Department of Natural History; CanadáFil: Otaola, Clara. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Saavedra 15. Instituto Multidisciplinario de Historia y Ciencias Humanas; ArgentinaFil: Gil, Adolfo Fabian. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Museo de Historia Natural de San Rafael - Ianigla | Provincia de Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Museo de Historia Natural de San Rafael - Ianigla | Universidad Nacional de Cuyo. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Museo de Historia Natural de San Rafael - Ianigla; ArgentinaFil: Paunero, Rafael. Universidad Nacional de La Plata; ArgentinaFil: Prevosti, Francisco Juan. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Regional de Investigaciones Científicas y Transferencia Tecnológica de La Rioja. - Universidad Nacional de La Rioja. Centro Regional de Investigaciones Científicas y Transferencia Tecnológica de La Rioja. - Universidad Nacional de Catamarca. Centro Regional de Investigaciones Científicas y Transferencia Tecnológica de La Rioja. - Secretaría de Industria y Minería. Servicio Geológico Minero Argentino. Centro Regional de Investigaciones Científicas y Transferencia Tecnológica de La Rioja. - Provincia de La Rioja. Centro Regional de Investigaciones Científicas y Transferencia Tecnológica de La Rioja; ArgentinaFil: Bradshaw, Corey J. A.. University of Adelaide; AustraliaFil: Wheeler, Jane C.. Instituto de Investigación y Desarrollo de Camélidos Sudamericanos; PerúFil: Borrero, Luis Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Saavedra 15. Instituto Multidisciplinario de Historia y Ciencias Humanas; ArgentinaFil: Austin, Jeremy J.. University of Adelaide; AustraliaFil: Cooper, Alan. University of Adelaide; Australia. University of Oxford; Reino Unid

The Human-Specific and Smooth Muscle Cell-Enriched LncRNA SMILR Promotes Proliferation by Regulating Mitotic CENPF mRNA and Drives Cell-Cycle Progression Which Can Be Targeted to Limit Vascular Remodeling.

RATIONALE: In response to blood vessel wall injury, aberrant proliferation of vascular smooth muscle cells (SMCs) causes pathological remodeling. However, the controlling mechanisms are not completely understood. OBJECTIVE: We recently showed that the human long noncoding RNA, SMILR, promotes vascular SMCs proliferation by a hitherto unknown mechanism. Here, we assess the therapeutic potential of SMILR inhibition and detail the molecular mechanism of action. METHODS AND RESULTS: We used deep RNA-sequencing of human saphenous vein SMCs stimulated with IL (interleukin)-1α and PDGF (platelet-derived growth factor)-BB with SMILR knockdown (siRNA) or overexpression (lentivirus), to identify SMILR-regulated genes. This revealed a SMILR-dependent network essential for cell cycle progression. In particular, we found using the fluorescent ubiquitination-based cell cycle indicator viral system that SMILR regulates the late mitotic phase of the cell cycle and cytokinesis with SMILR knockdown resulting in ≈10% increase in binucleated cells. SMILR pulldowns further revealed its potential molecular mechanism, which involves an interaction with the mRNA of the late mitotic protein CENPF (centromere protein F) and the regulatory Staufen1 RNA-binding protein. SMILR and this downstream axis were also found to be activated in the human ex vivo vein graft pathological model and in primary human coronary artery SMCs and atherosclerotic plaques obtained at carotid endarterectomy. Finally, to assess the therapeutic potential of SMILR, we used a novel siRNA approach in the ex vivo vein graft model (within the 30 minutes clinical time frame that would occur between harvest and implant) to assess the reduction of proliferation by EdU incorporation. SMILR knockdown led to a marked decrease in proliferation from ≈29% in controls to ≈5% with SMILR depletion. CONCLUSIONS: Collectively, we demonstrate that SMILR is a critical mediator of vascular SMC proliferation via direct regulation of mitotic progression. Our data further reveal a potential SMILR-targeting intervention to limit atherogenesis and adverse vascular remodeling

Ten-year mortality, disease progression, and treatment-related side effects in men with localised prostate cancer from the ProtecT randomised controlled trial according to treatment received

Background The ProtecT trial reported intention-to-treat analysis of men with localised prostate cancer randomly allocated to active monitoring (AM), radical prostatectomy, and external beam radiotherapy. Objective To report outcomes according to treatment received in men in randomised and treatment choice cohorts. Design, setting, and participants This study focuses on secondary care. Men with clinically localised prostate cancer at one of nine UK centres were invited to participate in the treatment trial comparing AM, radical prostatectomy, and radiotherapy. Intervention Two cohorts included 1643 men who agreed to be randomised and 997 who declined randomisation and chose treatment. Outcome measurements and statistical analysis Analysis was carried out to assess mortality, metastasis and progression and health-related quality of life impacts on urinary, bowel, and sexual function using patient-reported outcome measures. Analysis was based on comparisons between groups defined by treatment received for both randomised and treatment choice cohorts in turn, with pooled estimates of intervention effect obtained using meta-analysis. Differences were estimated with adjustment for known prognostic factors using propensity scores. Results and limitations According to treatment received, more men receiving AM died of PCa (AM 1.85%, surgery 0.67%, radiotherapy 0.73%), whilst this difference remained consistent with chance in the randomised cohort (p = 0.08); stronger evidence was found in the exploratory analyses (randomised plus choice cohort) when AM was compared with the combined radical treatment group (p = 0.003). There was also strong evidence that metastasis (AM 5.6%, surgery 2.4%, radiotherapy 2.7%) and disease progression (AM 20.35%, surgery 5.87%, radiotherapy 6.62%) were more common in the AM group. Compared with AM, there were higher risks of sexual dysfunction (95% at 6 mo) and urinary incontinence (55% at 6 mo) after surgery, and of sexual dysfunction (88% at 6 mo) and bowel dysfunction (5% at 6 mo) after radiotherapy. The key limitations are the potential for bias when comparing groups defined by treatment received and changes in the protocol for AM during the lengthy follow-up required in trials of screen-detected PCa. Conclusions Analyses according to treatment received showed increased rates of disease-related events and lower rates of patient-reported harms in men managed by AM compared with men managed by radical treatment, and stronger evidence of greater PCa mortality in the AM group. Patient summary More than 95 out of every 100 men with low or intermediate risk localised prostate cancer do not die of prostate cancer within 10 yr, irrespective of whether treatment is by means of monitoring, surgery, or radiotherapy. Side effects on sexual and bladder function are better after active monitoring, but the risks of spreading of prostate cancer are more common

Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity.

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant

Children’s and adolescents’ rising animal-source food intakes in 1990–2018 were impacted by age, region, parental education and urbanicity

Animal-source foods (ASF) provide nutrition for children and adolescents’ physical and cognitive development. Here, we use data from the Global Dietary Database and Bayesian hierarchical models to quantify global, regional and national ASF intakes between 1990 and 2018 by age group across 185 countries, representing 93% of the world’s child population. Mean ASF intake was 1.9 servings per day, representing 16% of children consuming at least three daily servings. Intake was similar between boys and girls, but higher among urban children with educated parents. Consumption varied by age from 0.6 at <1 year to 2.5 servings per day at 15–19 years. Between 1990 and 2018, mean ASF intake increased by 0.5 servings per week, with increases in all regions except sub-Saharan Africa. In 2018, total ASF consumption was highest in Russia, Brazil, Mexico and Turkey, and lowest in Uganda, India, Kenya and Bangladesh. These findings can inform policy to address malnutrition through targeted ASF consumption programmes.publishedVersio