The path from trigeminal asymmetry to cognitive impairment: a behavioral and molecular study

Trigeminal input exerts acute and chronic effects on the brain, modulating cognitive functions. Here, new data from humans and animals suggest that these effects are caused by trigeminal influences on the Locus Coeruleus (LC). In humans subjects clenching with masseter asymmetric activity, occlusal correction improved cognition, alongside with reductions in pupil size and anisocoria, proxies of LC activity and asymmetry, respectively. Notably, reductions in pupil size at rest on the hypertonic side predicted cognitive improvements. In adult rats, a distal unilateral section of the trigeminal mandibular branch reduced, on the contralateral side, the expression of c-Fos (brainstem) and BDNF (brainstem, hippocampus, frontal cortex). This counterintuitive finding can be explained by the following model: teeth contact perception loss on the lesioned side results in an increased occlusal effort, which enhances afferent inputs from muscle spindles and posterior periodontal receptors, spared by the distal lesion. Such effort leads to a reduced engagement of the intact side, with a corresponding reduction in the afferent inputs to the LC and in c-Fos and BDNF gene expression. In conclusion, acute effects of malocclusion on performance seem mediated by the LC, which could also contribute to the chronic trophic dysfunction induced by loss of trigeminal input

First measurement of the K−n →Λπ−non-resonant transition amplitude below threshold

We present the analysis of K−absorption processes on He4 leading to Λπ−final states, measured with the KLOE spectrometer at the DAΦNE e+e−collider and extract, for the first time, the modulus of the non-resonant K−n →Λπ−direct production amplitude about 33 MeV below the K‾N threshold. This analysis also allows to disentangle the K−nuclear absorption at-rest from the in-flight capture, for K−momenta of about 120 MeV. The data are interpreted with the help of a phenomenological model, and the modulus of the non-resonant K−n →Λπ−amplitude for K−absorption at-rest is found to be |AK−n→Λπ−|=(0.334±0.018stat−0.058+0.034syst)fm

Role of serum-free light chain assay for defining response and progression in immunoglobulin secretory multiple myeloma

The International Myeloma Working Group (IMWG) guidelines recommend using electrophoresis and immunofixation to define response and progressive disease (PD) in immunoglobulin (Ig) secretory multiple myeloma (Ig-MM), whereas the role of serum-free light chain (sFLC) is controversial. We retrospectively analyzed the value of adding sFLC assays in the definition of response and PD according to IMWG criteria in 339 Ig-MM patients treated with a first-line novel agent-based therapy (median follow-up 54 months). sFLC PD was defined according to conventional criteria plus increased sFLC levels, or sFLC escape (sFLCe); progression/sFLCe-free survival (ePFS) was the time from the start of treatment to the date of first PD or sFLCe, or death; overall survival after PD/sFLCe (OS after Pe) was the time from first PD or sFLCe to the date of death. 148 (44%) patients achieved a complete response and 198 (60%) a normal sFLC ratio (sFLCR). sFLCR normalization was an independent prognostic factor for extended PFS (HR = 0.46, p = 0.001) and OS (HR = 0.47, p = 0.006) by multivariable analysis. 175 (52%) patients experienced PD according to the IMWG criteria, whereas 180 (53%) experienced PD or sFLCe. Overall, a sFLCe was observed in 31 (9%) patients. Median PFS and ePFS were both equal to 36 (95% CI = 32–42, and 32–40, respectively) months. sFLC PD adversely affected the OS after Pe compared to PD with increasing monoclonal Ig only (HR = 0.52, p = 0.012). Our results support the inclusion of the sFLC assay for defining response and PD in Ig-MM

Search for dark Higgsstrahlung in e+ e- -> mu+ mu- and missing energy events with the KLOE experiment

We searched for evidence of a Higgsstrahlung process in a secluded sector, leading to a final state with a dark photon U and a dark Higgs boson h', with the KLOE detector at DAFNE. We investigated the case of h' lighter than U, with U decaying into a muon pair and h' producing a missing energy signature. We found no evidence of the process and set upper limits to its parameters in the range 2m_mu<m_U<1000 MeV, m_h'<m_U.Comment: 16 pages, 7 figures, submitted to Physics Letters

Limit on the production of a new vector boson in e+e−→Uγ\mathrm{e^+ e^-}\rightarrow {\rm U}\gamma, U→π+π−\rightarrow \pi^+\pi^- with the KLOE experiment

The recent interest in a light gauge boson in the framework of an extra U(1) symmetry motivates searches in the mass range below 1 GeV. We present a search for such a particle, the dark photon, in ${\rm e^+ e^-}\rightarrow {\rm U}\gamma$, U$\rightarrow \pi^+\pi^-$ based on 28 million $\mathrm{e^+ e^-} \rightarrow \pi^+ \pi^-\gamma$ events collected at DA$\Phi$NE by the KLOE experiment. The $\pi^+ \pi^-$ production by initial-state radiation compensates for a loss of sensitivity of previous KLOE ${\rm U} \rightarrow \mathrm{e^+ e^-}$, $\mu^+\mu^-$ searches due to the small branching ratios in the $\rho-\omega$ resonance region. We found no evidence for a signal and set a limit at 90\% CL on the mixing strength between the photon and the dark photon, $\varepsilon^2$, in the U mass range between $527$ and $987$~MeV. Above 700 MeV this new limit is more stringent than previous ones.Comment: 6 pages, 9 figures, 1 table, submitted to Phys. Lett.

Measurement of the ϕ→π0e+e−\phi \to \pi^0 e^+e^- transition form factor with the KLOE detector

A measurement of the vector to pseudoscalar conversion decay $\phi \to \pi^0 e^+e^-$ with the KLOE experiment is presented. A sample of $\sim 9500$ signal events was selected from a data set of 1.7 fb$^{-1}$ of $e^+e^-$ collisions at $\sqrt{s} \sim m_{\phi}$ collected at the DA$\Phi$NE $e^+e^-$ collider. These events were used to obtain the first measurement of the transition form factor $| F_{\phi \pi^0}(q^2) |$ and a new measurement of the branching ratio of the decay: $\rm{BR}\,(\phi \to \pi^0 e^+e^-) = (\,1.35 \pm 0.05^{\,\,+0.05}_{\,\,-0.10}\,) \times 10 ^{-5}$. The result improves significantly on previous measurements and is in agreement with theoretical predictions.Comment: 13 pages, 4 figures; matches published versio

Defining the genomic signature of the parous breast.

ABSTRACT: BACKGROUND: It is accepted that a woman's lifetime risk of developing breast cancer after menopause is reduced by early full term pregnancy and multiparity. This phenomenon is thought to be associated with the development and differentiation of the breast during pregnancy. METHODS: In order to understand the underlying molecular mechanisms of pregnancy induced breast cancer protection, we profiled and compared the transcriptomes of normal breast tissue biopsies from 71 parous (P) and 42 nulliparous (NP) healthy postmenopausal women using Affymetrix Human Genome U133 Plus 2.0 arrays. To validate the results, we performed real time PCR and immunohistochemistry. RESULTS: We identified 305 differentially expressed probesets (208 distinct genes). Of these, 267 probesets were up- and 38 down-regulated in parous breast samples; bioinformatics analysis using gene ontology enrichment revealed that up-regulated genes in the parous breast represented biological processes involving differentiation and development, anchoring of epithelial cells to the basement membrane, hemidesmosome and cell-substrate junction assembly, mRNA and RNA metabolic processes and RNA splicing machinery. The down-regulated genes represented biological processes that comprised cell proliferation, regulation of IGF-like growth factor receptor signaling, somatic stem cell maintenance, muscle cell differentiation and apoptosis. CONCLUSIONS: This study suggests that the differentiation of the breast imprints a genomic signature that is centered in the mRNA processing reactome. These findings indicate that pregnancy may induce a safeguard mechanism at post-transcriptional level that maintains the fidelity of the transcriptional process

Precision measurement of the η→π+π−π0\eta\to\pi^+\pi^-\pi^0 Dalitz plot distribution with the KLOE detector

Using $1.6$ fb$^{-1}$ of $e^+ e^-\to\phi\to\eta\gamma$ data collected with the KLOE detector at DA$\Phi$NE, the Dalitz plot distribution for the $\eta \to \pi^+ \pi^- \pi^0$ decay is studied with the world's largest sample of $\sim 4.7 \cdot 10^6$ events. The Dalitz plot density is parametrized as a polynomial expansion up to cubic terms in the normalized dimensionless variables $X$ and $Y$. The experiment is sensitive to all charge conjugation conserving terms of the expansion, including a $gX^2Y$ term. The statistical uncertainty of all parameters is improved by a factor two with respect to earlier measurements.Comment: 11 pages, 9 figures, supplement: an ascii tabl