Rubinstein-Taybi syndrome with scoliosis

<p>Abstract</p> <p>Study Design</p> <p>Case report.</p> <p>Objective</p> <p>The authors present the case of a 14-year-old boy with Rubinstein-Taybi syndrome (RSTS) presenting scoliosis.</p> <p>Summary of Background Data</p> <p>There have been no reports on surgery for RSTS presenting scoliosis.</p> <p>Methods</p> <p>The patient was referred to our hospital for evaluation of a progressive spinal curvature. A standing anteroposterior spine radiograph at presentation to our hospital revealed an 84-degree right thoracic curve from T6 to T12, along with a 63-degree left lumbar compensatory curve from T12 to L4. We planned a two-staged surgery and decided to fuse from T4 to L4. The first operation was front-back surgery because of the rigidity of the right thoracic curve. The second operation of lumbar anterior discectomy and fusion was arranged 9 months after the first surgery to prevent the crankshaft phenomenon due to his natural course of adolescent growth. To avoid respiratory complications, the patient was put on a respirator in the ICU for several days after both surgeries.</p> <p>Results</p> <p>Full-length spine radiographs after the first surgery revealed no instrumentation failure and showed that the right thoracic curve was corrected to 31 degrees and the left lumbar curve was corrected to 34 degrees. No postoperative complications occurred after both surgeries.</p> <p>Conclusions</p> <p>We succeeded in treating the patient without complications. Full-length spine standing radiographs at one year after the second operation demonstrated a stable bony arthrodesis with no loss of initial correction.</p

H_2 emission arises outside photodissociation regions in ultra-luminous infrared galaxies

Ultra-luminous infrared galaxies are among the most luminous objects in the local universe and are thought to be powered by intense star formation. It has been shown that in these objects the rotational spectral lines of molecular hydrogen observed at mid-infrared wavelengths are not affected by dust obscuration, leaving unresolved the source of excitation of this emission. Here I report an analysis of archival Spitzer Space Telescope data on ultra-luminous infrared galaxies and demonstrate that star formation regions are buried inside optically thick clouds of gas and dust, so that dust obscuration affects star-formation indicators but not molecular hydrogen. I thereby establish that the emission of H_2 is not co-spatial with the buried starburst activity and originates outside the obscured regions. This is rather surprising in light of the standard view that H_2 emission is directly associated with star-formation activity. Instead, I propose that H_2 emission in these objects traces shocks in the surrounding material, which are in turn excited by interactions with nearby galaxies, and that powerful large-scale shocks cooling by means of H_2 emission may be much more common than previously thought. In the early universe, a boost in H_2 emission by this process may speed up the cooling of matter as it collapsed to form the first stars and galaxies and would make these first structures more readily observable.Comment: Main text and supplemental information, 21 pages including 6 figures, 2 table

HIV vaccine: it may take two to tango, but no party time yet

A press conference on Thursday September 24 in Bangkok, Thailand, released data that an experimental vaccine provided mild protection against HIV-1 infection. This is the first positive signal of any degree of vaccine efficacy in humans, more than a quarter-century after scientists discovered the virus that causes AIDS. The research was conducted by a team including Thai researchers, the U.S. Army and the U.S. National Institutes of Health. The RV144 Phase III clinical trial, which began in 2003, had been disparaged by many critics as a waste of time and money because each of the two components had been shown to produce no benefit as individual vaccines and because the scientific rationales behind the immunogens were just wrong. It was nevertheless speculated that using them together in the prime-boost scenario could be more effective, with the aim to induce heightened CD4+ cellular immune responses against the viral Envelope protein. This optimism seems to have been validated. In fact, this would not be the first time that the discovery of an effective vaccine relied as much on serendipity as opposed to scientific rationale. On the other hand, many questions remain about the RV144 trial, and these issues will be addressed in this editorial

Predictive validity of the CriSTAL tool for short-term mortality in older people presenting at Emergency Departments: a prospective study

© 2018, The Author(s). Abstract: To determine the validity of the Australian clinical prediction tool Criteria for Screening and Triaging to Appropriate aLternative care (CRISTAL) based on objective clinical criteria to accurately identify risk of death within 3 months of admission among older patients. Methods: Prospective study of ≥ 65 year-olds presenting at emergency departments in five Australian (Aus) and four Danish (DK) hospitals. Logistic regression analysis was used to model factors for death prediction; Sensitivity, specificity, area under the ROC curve and calibration with bootstrapping techniques were used to describe predictive accuracy. Results: 2493 patients, with median age 78–80 years (DK–Aus). The deceased had significantly higher mean CriSTAL with Australian mean of 8.1 (95% CI 7.7–8.6 vs. 5.8 95% CI 5.6–5.9) and Danish mean 7.1 (95% CI 6.6–7.5 vs. 5.5 95% CI 5.4–5.6). The model with Fried Frailty score was optimal for the Australian cohort but prediction with the Clinical Frailty Scale (CFS) was also good (AUROC 0.825 and 0.81, respectively). Values for the Danish cohort were AUROC 0.764 with Fried and 0.794 using CFS. The most significant independent predictors of short-term death in both cohorts were advanced malignancy, frailty, male gender and advanced age. CriSTAL’s accuracy was only modest for in-hospital death prediction in either setting. Conclusions: The modified CriSTAL tool (with CFS instead of Fried’s frailty instrument) has good discriminant power to improve prognostic certainty of short-term mortality for ED physicians in both health systems. This shows promise in enhancing clinician’s confidence in initiating earlier end-of-life discussions

Disruption of Ant-Aphid Mutualism in Canopy Enhances the Abundance of Beetles on the Forest Floor

Ant-aphid mutualism is known to play a key role in the structure of the arthropod community in the tree canopy, but its possible ecological effects for the forest floor are unknown. We hypothesized that aphids in the canopy can increase the abundance of ants on the forest floor, thus intensifying the impacts of ants on other arthropods on the forest floor. We tested this hypothesis in a deciduous temperate forest in Beijing, China. We excluded the aphid-tending ants Lasius fuliginosus from the canopy using plots of varying sizes, and monitored the change in the abundance of ants and other arthropods on the forest floor in the treated and control plots. We also surveyed the abundance of ants and other arthropods on the forest floor to explore the relationships between ants and other arthropods in the field. Through a three-year experimental study, we found that the exclusion of ants from the canopy significantly decreased the abundance of ants on the forest floor, but increased the abundance of beetles, although the effect was only significant in the large ant-exclusion plot (80*60 m). The field survey showed that the abundance of both beetles and spiders was negatively related to the abundance of ants. These results suggest that aphids located in the tree canopy have indirect negative effects on beetles by enhancing the ant abundance on the forest floor. Considering that most of the beetles in our study are important predators, the ant-aphid mutualism can have further trophic cascading effects on the forest floor food web

Polymorphisms in Toll-Like Receptors 2, 4, and 9 Are Highly Associated with Hearing Loss in Survivors of Bacterial Meningitis

Genetic variation in innate immune response genes contributes to inter-individual differences in disease manifestation and degree of complications upon infection. We recently described an association of single nucleotide polymorphisms (SNPs) in TLR9 with susceptibility to meningococcal meningitis (MM). In this study, we investigate the association of SNPs in multiple pathogen recognition and immune response genes with clinical features that determine severity and outcome (especially hearing loss) of childhood MM and pneumococcal meningitis (PM). Eleven SNPs in seven genes (TLR2, TLR4, TLR9, NOD1, NOD2, CASP1, and TRAIL) were genotyped in 393 survivors of childhood bacterial meningitis (BM) (327 MM patients and 66 PM patients). Genotype distributions of single SNPs and combination of SNPs were compared between thirteen clinical characteristics associated with severity of BM. After correction for multiple testing, TLR4+896 mutant alleles were highly associated with post-meningitis hearing loss, especially MM (p  = 0.001, OR 4.0 for BM, p  = 0.0004, OR 6.2 for MM). In a multigene analysis, combined carriership of the TLR2+2477 wild type (WT) with TLR4+896 mutant alleles increases the risk of hearing loss (p<0.0001, OR 5.7 in BM and p  = 0.0001, OR 7.6 in MM). Carriage of one or both mutant alleles in TLR4+896 and TLR9 -1237 increases the risk for hearing loss (p  = 0.0006, OR 4.1 in BM). SNPs in immune response genes contribute to differences in clinical severity and outcome of BM. The TLR system seems to play an important role in the immune response to BM and subsequent neuronal damage as well as in cochlear inflammation. Genetic markers may be used for identification of high-risk patients by creating prediction rules for post-meningitis hearing loss and other sequelae, and provide more insight in the complex immune response in the CNS possibly resulting in new therapeutic interventions

Toll-like receptor 9 polymorphisms are associated with severity variables in a cohort of meningococcal meningitis survivors

BACKGROUND: Genetic variation in immune response genes is associated with susceptibility and severity of infectious diseases. Toll-like receptor (TLR) 9 polymorphisms are associated with susceptibility to develop meningococcal meningitis (MM). The aim of this study is to compare genotype distributions of two TLR9 polymorphisms between clinical severity variables in MM survivors. METHODS: We used DNA samples of a cohort of 390 children who survived MM. Next, we determined the genotype frequencies of TLR9 -1237 and TLR9 +2848 polymorphisms and compared these between thirteen clinical variables associated with prognostic factors predicting adverse outcome of bacterial meningitis in children. RESULTS: The TLR9 -1237 TC and CC genotypes were associated with a decreased incidence of a positive blood culture for Neisseria (N.) meningitidis (p = 0.014, odds ratio (OR) 0.5. 95% confidence interval (CI) 0.3 – 0.9). The TLR9 +2848 AA mutant was associated with a decreased incidence of a positive blood culture for N. meningitidis (p = 0.017, OR 0.6, 95% CI 0.3 – 0.9). Cerebrospinal fluid (CSF) leukocytes per μL were higher in patients carrying the TLR9 -1237 TC or CC genotypes compared to carriers of the TT wild type (WT) (p = 0.024, medians: 2117, interquartile range (IQR) 4987 versus 955, IQR 3938). CSF blood/glucose ratios were lower in TLR9 -1237 TC or CC carriers than in carriers of the TT WT (p = 0.017, medians: 0.20, IQR 0.4 versus 0.35, IQR 0.5). CSF leukocytes/μL were higher in patients carrying the TLR9 +2848 AA mutant compared to carriers of GG or GA (p = 0.0067, medians: 1907, IQR 5221 versus 891, IQR 3952). CONCLUSIONS: We identified TLR9 genotypes associated with protection against meningococcemia and enhanced local inflammatory responses inside the central nervous system, important steps in MM pathogenesis and defense

Large-scale associations between the leukocyte transcriptome and BOLD responses to speech differ in autism early language outcome subtypes.

Heterogeneity in early language development in autism spectrum disorder (ASD) is clinically important and may reflect neurobiologically distinct subtypes. Here, we identified a large-scale association between multiple coordinated blood leukocyte gene coexpression modules and the multivariate functional neuroimaging (fMRI) response to speech. Gene coexpression modules associated with the multivariate fMRI response to speech were different for all pairwise comparisons between typically developing toddlers and toddlers with ASD and poor versus good early language outcome. Associated coexpression modules were enriched in genes that are broadly expressed in the brain and many other tissues. These coexpression modules were also enriched in ASD-associated, prenatal, human-specific, and language-relevant genes. This work highlights distinctive neurobiology in ASD subtypes with different early language outcomes that is present well before such outcomes are known. Associations between neuroimaging measures and gene expression levels in blood leukocytes may offer a unique in vivo window into identifying brain-relevant molecular mechanisms in ASD

Genome-wide association study of male sexual orientation

Family and twin studies suggest that genes play a role in male sexual orientation. We conducted a genome-wide association study (GWAS) of male sexual orientation on a primarily European ancestry sample of 1,077 homosexual men and 1,231 heterosexual men using Affymetrix single nucleotide polymorphism (SNP) arrays. We identified several SNPs with p < 10 -5 , including regions of multiple supporting SNPs on chromosomes 13 (minimum p = 7.5 × 10 -7 ) and 14 (p = 4.7 × 10 -7 ). The genes nearest to these peaks have functions plausibly relevant to the development of sexual orientation. On chromosome 13, SLITRK6 is a neurodevelopmental gene mostly expressed in the diencephalon, which contains a region previously reported as differing in size in men by sexual orientation. On chromosome 14, TSHR genetic variants in intron 1 could conceivably help explain past findings relating familial atypical thyroid function and male homosexuality. Furthermore, skewed X chromosome inactivation has been found in the thyroid condition, Graves' disease, as well as in mothers of homosexual men. On pericentromeric chromosome 8 within our previously reported linkage peak, we found support (p = 4.1 × 10 -3 ) for a SNP association previously reported (rs77013977, p = 7.1 × 10 -8 ), with the combined analysis yielding p = 6.7 × 10 -9 , i.e., a genome-wide significant association