Activity

Relapse of neonatal meningitis is most commonly caused by Escherichia coli. Management to prevent relapse varies and evidence is limited. We present four cases of relapsing neonatal E. coli meningitis in Denmark in 2016-2017 and review the current literature on this subject. During the primary episodes, our patients received cephalosporin for 3 weeks and gentamicin for the first 3 days. The only identified risk factor was delayed CSF sterilization in three of four cases and no repeated lumbar puncture. Relapse occurred after 2-28 days; one case with ventriculitis and one with empyema. Relapses were treated for 6-14 weeks with monotherapy. No children had an underlying disease predisposing to E. coli meningitis. There is generally a trend towards reducing invasive procedures, e.g., lumbar puncture and the length of intravenous antibiotics in pediatric infectious diseases, but our cases highlight a condition where the opposite might be needed.Breast cancer is the most common cancer in women, but its incidence can only be partially explained through established risk factors. Our aim was to use metabolomics to identify novel risk factors for breast cancer and to validate recently reported metabolite-breast cancer findings. We measured levels of 1275 metabolites in prediagnostic serum in a nested case-control study of 782 postmenopausal breast cancer cases and 782 matched controls. Metabolomics analysis was performed by Metabolon Inc using ultra-performance liquid chromatography and a Q-Exactive high resolution/accurate mass spectrometer. Controls were matched by birth date, date of blood draw, and race/ethnicity. Odds ratios (ORs) and 95% confidence intervals (CIs) of breast cancer at the 90th versus 10th percentile (modeled on a continuous basis) of metabolite levels were estimated using conditional logistic regression, with adjustment for age. Twenty-four metabolites were significantly associated with breast cancer risk at a false discovery rate less then 0.20. For the nine metabolites positively associated with risk, the ORs ranged from 1.75 (95% CI 1.29-2.36) to 1.45 (95% CI 1.13-1.85), and for the 15 metabolites inversely associated with risk, ORs ranged from 0.59 (95% CI 0.43-0.79) to 0.69 (95% CI 0.55-0.87). These metabolites largely comprised carnitines, glycerolipids, and sex steroid metabolites. Associations for three sex steroid metabolites validated findings from recent studies and the remainder were novel. These findings contribute to growing data on metabolite-breast cancer associations by confirming prior findings and identifying novel leads for future validation efforts.In the fish genus Hoplias, two major general groups can be found, one of which is formed by the “common trahiras” (Hoplias malabaricus group) and the other by the “giant trahiras” (Hoplias lacerdae group, in addition to Hoplias aimara), which usually comprises specimens of larger body size. Previous investigations from the giant trahiras group recovered 2n = 50 meta/submetacentric chromosomes and no sex chromosome differentiation, indicating a probable conservative pattern for their karyotype organization. Here, we conducted comparative cytogenetic studies in six giant trahiras species, two of them for the first time. AZD1656 mouse We employed standard and advanced molecular cytogenetics procedures, including comparative genomic hybridization (CGH), as well as genomic assessments of diversity levels and phylogenetic relationships among them. The results strongly suggest that the giant trahiras have a particular and differentiated evolutionary pathway inside the Hoplias genus. While these species share the same 2n and karyotypes, their congeneric species of the H. malabaricus group show a notable chromosomal diversity in number, morphology, and sex chromosome systems. However, at the same time, significant changes were characterized at their inner chromosomal level, as well as in their genetic diversity, highlighting their current relationships resulting from different evolutionary histories.Despite recent advances in first-line treatment for small-cell lung cancer (SCLC), durable responses remain rare. The DNA repair enzyme poly-(ADP)-ribose polymerase (PARP) was identified as a therapeutic target in SCLC using unbiased preclinical screens and confirmed in human and mouse models. Early trials of PARP inhibitors, either alone or in combination with chemotherapy, showed promising but limited responses, suggesting that selecting patient subsets and treatment combinations will prove critical to further clinical development. Expression of SLFN11 and other components of the DNA damage response (DDR) pathway appears to select for improved responses. Combining PARP inhibitors with agents that damage DNA and inhibit DDR appears particularly effective in preclinical and early trial data, as well as strategies that enhance antitumor immunity downstream of DNA damage. A robust understanding of the mechanisms of DDR in SCLC, which exhibits intrinsic replication stress, will improve selection of agents and predictive biomarkers. The most effective combinations will target multiple nodes in the DNA damage/DDR/immune activation cascade to minimize toxicity from synthetic lethality.Despite the well-known favorable chemical and mechanical properties of titanium-based materials for orthopedic and dental applications, poor osseointegration of the implants, bacteria adhesion, and excessive inflammatory response from the host remain major problems to be solved. Here, the antioxidant and anti-inflammatory enzyme-like abilities of ceria (CeOx) were coupled to the advantageous features of titanium nanotubes (TiNTs). Cost-effective and fast methods, such as electrochemical anodization and drop casting, were used to build active surfaces with enhanced bioactivity. Surface composition, electrochemical response, and in vitro ability to induce hydroxyapatite (HA) precipitation were evaluated. The amount of cerium in the coating did not significantly affect wettability, yet a growing ability to induce early HA precipitation from simulated body fluid (SBF) was observed as the oxide content at the surface increased. The presence of 4%wt CeOx was also able to stimulate rapid HA maturation in a (poorly) crystalline form, indicating an interesting potential to induce rapid in vivo osseointegration process.