Skeletal muscle overexpression of sAnk1.5 in transgenic mice does not predispose to type 2 diabetes.

Genome-wide association studies (GWAS) and cis-expression quantitative trait locus (cis-eQTL) analyses indicated an association of the rs508419 single nucleotide polymorphism (SNP) with type 2 diabetes (T2D). rs508419 is localized in the muscle-specific internal promoter (P2) of the ANK1 gene, which drives the expression of the sAnk1.5 isoform. Functional studies showed that the rs508419 C/C variant results in increased transcriptional activity of the P2 promoter, leading to higher levels of sAnk1.5 mRNA and protein in skeletal muscle biopsies of individuals carrying the C/C genotype. To investigate whether sAnk1.5 overexpression in skeletal muscle might predispose to T2D development, we generated transgenic mice (TgsAnk1.5/+) in which the sAnk1.5 coding sequence was selectively overexpressed in skeletal muscle tissue. TgsAnk1.5/+ mice expressed up to 50% as much sAnk1.5 protein as wild-type (WT) muscles, mirroring the difference reported between individuals with the C/C or T/T genotype at rs508419. However, fasting glucose levels, glucose tolerance, insulin levels and insulin response in TgsAnk1.5/+ mice did not differ from those of age-matched WT mice monitored over a 12-month period. Even when fed a high-fat diet, TgsAnk1.5/+ mice only presented increased caloric intake, but glucose disposal, insulin tolerance and weight gain were comparable to those of WT mice fed a similar diet. Altogether, these data indicate that sAnk1.5 overexpression in skeletal muscle does not predispose mice to T2D susceptibility.

Three-dimensional facial swelling evaluation of piezo-electric vs conventional drilling bur surgery of impacted lower third molar: a randomized clinical trial.

BACKGROUND: Among the post-surgical complications of lower wisdom teeth surgery, swelling is considered by patients one of the most impairing, with both social and biological influences and impacting patients' quality of life. Aim of the study was to evaluate the swelling following the osteotomy when performed with drilling burs versus piezo-electric instruments in the mandibular impacted third molar extraction, using a facial reconstruction software. MATERIALS AND METHODS: A randomized, split-mouth, single-blind study was conducted on patients, ranging between 18 and 40 years of age, requiring lower third molars extraction and referred at the Oral Surgery Unit of the School of Dentistry of the University of Messina. Twenty-two patients were recruited during an 8 months period according to the following criteria: good general health conditions; bilateral, symmetrical, impacted third molars; no use of medication that would influence or alter wound healing; no temporomandibular joint disorder history; no smoking. All patients underwent bilateral surgical removal. For each patient, a facial scan was obtained prior to the surgical procedures. The two extractions were conducted performing, in a randomized way, osteotomy with rotatory burs or use of piezo surgical instruments. Facial scans were repeated at 3 and 7 days after the surgical procedures. Volumetric differences were calculated via superimposition using a dedicated software. The data obtained were processed using paired t-test. RESULTS: The results obtained from our study showed no significant differences between two groups regarding post-operative swelling. To the best of our knowledge, this study represents the first experience of using an objective method that can be reproducible on the collection of patients' clinical parameters. CONCLUSIONS: The 3D digital analysis, in the evaluation of facial swelling, is a technique of simple application, objective, reproducible, reliable, decreasing the variables of error. Based on these data, it is possible to conclude that piezo surgery is a safe way for performing the osteotomies during third molar surgery. However, regarding the post-operative swelling, it does not show an advantage over classical rotary instruments. TRIAL REGISTRATION: Registered on ClinicalTrials.gov (ID: NCT05488028, on 04/08/2022). Approved by Ethical Committee of Messina: (ID 01-2020, on 27/04/2020).

Crossing N=28 Toward the Neutron Drip Line: First Measurement of Half-Lives at FRIB.

New half-lives for exotic isotopes approaching the neutron drip-line in the vicinity of N∼28 for Z=12-15 were measured at the Facility for Rare Isotope Beams (FRIB) with the FRIB decay station initiator. The first experimental results are compared to the latest quasiparticle random phase approximation and shell-model calculations. Overall, the measured half-lives are consistent with the available theoretical descriptions and suggest a well-developed region of deformation below ^{48}Ca in the N=28 isotones. The erosion of the Z=14 subshell closure in Si is experimentally confirmed at N=28, and a reduction in the ^{38}Mg half-life is observed as compared with its isotopic neighbors, which does not seem to be predicted well based on the decay energy and deformation trends. This highlights the need for both additional data in this very exotic region, and for more advanced theoretical efforts.

Evidence of a Near-Threshold Resonance in

A narrow near-threshold proton-emitting resonance (E_{x}=11.4 MeV, J^{π}=1/2^{+}, and Γ_{p}=4.4 keV) was directly observed in ^{11}B via proton resonance scattering. This resonance was previously inferred in the ß-delayed proton emission of the neutron halo nucleus ^{11}Be. The good agreement between both experimental results serves as a ground to confirm the existence of such exotic decay and the particular behavior of weakly bound nuclei coupled to the continuum. R-matrix analysis shows a sizable partial decay width for both, proton and α (Γ_{α}=11 keV) emission channels.

A novel neurocognitive approach for placebo analgesia in neurocognitive disorders.

Neural correlates of placebo analgesia (PA) in patients with neurocognitive disorders have not yet been elucidated. The present study aimed to evaluate how and to what extent executive (dys)functions of the medial prefrontal cortex (MPFC) may be related to PA. To this end, twenty-three subjects complaining of different cognitive deficits (from mild cognitive impairment likely due to Alzheimer's disease to mild AD) were recruited. PA was investigated by a well-known experimental venipuncture pain paradigm (open versus hidden [O-H] application of lidocaine). Patients also underwent a comprehensive neuropsychological evaluation and a functional magnetic resonance imaging (fMRI) GO/No-GO task for eliciting selective activation of the MPFC. Selected neuropsychological variables were correlated to the OH-PA paradigm. The association between the fMRI response on the "No-GO" versus "GO" contrast and PA was investigated over the whole-brain by regression analysis. We showed the existence of a relationship between a lower PA and MPFC dysfunctions through the neuropsychological and fMRI assessment. A separate voxel-based morphometry (VBM) analysis controlled for possible influence of grey matter (GM) volume reduction on both fMRI results and PA. fMRI results were not directly affected by, and therefore independent of, disease-specific GM atrophy, which was indeed located more anteriorly within the rostral anterior cingulate and inversely correlated with PA. Our findings shed new light on the underestimated contribution of executive (dys)functions mediated by the MPFC (response-inhibition, self-monitoring and set-shifting abilities) in PA pathogenesis, with a special purely (i.e. independently from brain structural alterations) functional role played by the MCC. Results are discussed in terms of possible clinical relevance in the management of patients with neurocognitive disorders.

Prevalence and phenotype of the c.1529C>T SPG7 variant in adult-onset cerebellar ataxia in Italy.

BACKGROUND AND PURPOSE: Hereditary ataxias are heterogeneous groups of neurodegenerative disorders, characterized by cerebellar syndromes associated with dysarthria, oculomotor and corticospinal signs, neuropathy and cognitive impairment. Recent reports have suggested mutations in the SPG7 gene, causing the most common form of autosomal recessive spastic paraplegia (MIM#607259), as a main cause of ataxias. The majority of described patients were homozygotes or compound heterozygotes for the c.1529C>T (p.Ala510Val) change. We screened a cohort of 895 Italian patients with ataxia for p.Ala510Val in order to define the prevalence and genotype-phenotype correlation of this variant. METHODS: We set up a rapid assay for c.1529C>T using restriction enzyme analysis after polymerase chain reaction amplification. We confirmed the diagnosis with Sanger sequencing. RESULTS: We identified eight homozygotes and 13 compound heterozygotes, including two novel variants affecting splicing. Mutated patients showed a pure cerebellar ataxia at onset, evolving in mild spastic ataxia (alternatively) associated with dysarthria (~80% of patients), urinary urgency (~30%) and pyramidal signs (~70%). Comparing homozygotes and compound heterozygotes, we noted a difference in age at onset and Scale for the Assessment and Rating of Ataxia score between the two groups, supporting an earlier and more severe phenotype in compound heterozygotes versus homozygotes. CONCLUSIONS: The SPG7 c.1529C>T (p.Ala510Val) mutants accounted for 2.3% of cerebellar ataxia cases in Italy, suggesting that this variant should be considered as a priority test in the presence of late-onset pure ataxia. Moreover, the heterozygous/homozygous genotype appeared to predict the onset of clinical manifestation and disease progression.

Recent advances in the molecular genetics of frontotemporal lobar degeneration.

The term frontotemporal lobar degeneration (FTLD) describes a spectrum of neurodegenerative disorders associated with deposition of misfolded proteins in the frontal and temporal lobes. Up to 40% of FTLD patients reports a family history of neurodegeneration, and approximately 1/3 of familial cases shows an autosomal dominant pattern of inheritance of the phenotype. Over the past two decades, several causative and susceptibility genes for FTLD have been discovered, supporting the notion that genetic factors are important contributors to the disease processes. Genetic variants in three genes, MAPT, GRN and C9orf72, account for about half of familial FTLD cases. In addition, rare defects in the CHMP2B, VCP, TARDBP, SQSTM1, FUS, UBQLN, OPTN, TREM2, CHCHD10 and TBK1 genes have been described. Additional genes are expected to be found in near future. The purpose of this review is to describe recent advances in the molecular genetics of the FTLD spectrum and to discuss implications for genetic counseling.

Blackbody emission from light interacting with an effective moving dispersive medium.

Intense laser pulses excite a nonlinear polarization response that may create an effective flowing medium and, under appropriate conditions, a blocking horizon for light. Here, we analyze in detail the interaction of light with such laser-induced flowing media, fully accounting for the medium dispersion properties. An analytical model based on a first Born approximation is found to be in excellent agreement with numerical simulations based on Maxwell's equations and shows that when a blocking horizon is formed, the stimulated medium scatters light with a blackbody emission spectrum. Based on these results, diamond is proposed as a promising candidate medium for future studies of Hawking emission from artificial, dispersive horizons.

Soliton-induced relativistic-scattering and amplification.

Solitons are of fundamental importance in photonics due to applications in optical data transmission and also as a tool for investigating novel phenomena ranging from light generation at new frequencies and wave-trapping to rogue waves. Solitons are also moving scatterers: they generate refractive index perturbations moving at the speed of light. Here we found that such perturbations scatter light in an unusual way: they amplify light by the mixing of positive and negative frequencies, as we describe using a first Born approximation and numerical simulations. The simplest scenario in which these effects may be observed is within the initial stages of optical soliton propagation: a steep shock front develops that may efficiently scatter a second, weaker probe pulse into relatively intense positive and negative frequency modes with amplification at the expense of the soliton. Our results show a novel all-optical amplification scheme that relies on soliton induced scattering.

Cavitation dynamics and directional microbubble ejection induced by intense femtosecond laser pulses in liquids.

We study cavitation dynamics when focusing ring-shaped femtosecond laser beams in water. This focusing geometry reduces detrimental nonlinear beam distortions and enhances energy deposition within the medium, localized at the focal spot. We observe remarkable postcollapse dynamics of elongated cavitation bubbles with high-speed ejection of microbubbles out of the laser focal region. Bubbles are ejected along the laser axis in both directions (away and towards the laser). The initial shape of the cavitation bubble is also seen to either enhance or completely suppress jet formation during collapse. In the absence of jetting, microbubble ejection occurs orthogonal to the laser propagation axis.

Negative-frequency resonant radiation.

Optical solitons or solitonlike states shed light to blueshifted frequencies through a resonant emission process. We predict a mechanism by which a second propagating mode is generated. This mode, called negative resonant radiation, originates from the coupling of the soliton mode to the negative-frequency branch of the dispersion relation. Measurements in both bulk media and photonic-crystal fibers confirm our predictions.

Generation of broadly tunable sub-30-fs infrared pulses by four-wave optical parametric amplification.

We report on the generation of sub-30-fs near-IR light pulses by means of broadband four-wave parametric amplification in fused silica. This is achieved by frequency downconversion of visible broadband pulses provided by a commercial blue-pumped beta-barium borate crystal-based noncollinear optical parametric amplifier. The proposed method produces the IR idler pulses with energy up to ∼20 µJ and tunable in wavelength from 1 to 1.5 µm. The shortest pulse duration is 17.6 fs, measured at 1.2 µm.

Space-time focusing of Bessel-like pulses.

We report on a space-time compression technique allowing for complete and independent control of the longitudinal dynamics and of the transverse pulse localization by means of spatial beam shaping. We experimentally observe both strong temporal compression and high transverse localization, of the order of a few wavelengths, along free-space propagation.

Worldwide distribution of PSEN1 Met146Leu mutation: a large variability for a founder mutation.

OBJECTIVE: Large kindreds segregating familial Alzheimer disease (FAD) offer the opportunity of studying clinical variability as observed for presenilin 1 (PSEN1) mutations. Two early-onset FAD (EOFAD) Calabrian families with PSEN1 Met146Leu (ATG/CTG) mutation constitute a unique population descending from a remote common ancestor. Recently, several other EOFAD families with the same mutation have been described worldwide. METHODS: We searched for a common founder of the PSEN1 Met146Leu mutation in families with different geographic origins by genealogic and molecular analyses. We also investigated the phenotypic variability at onset in a group of 50 patients (mean age at onset 40.0 +/- 4.8 years) by clinical, neuropsychological, and molecular methodologies. RESULTS: EOFAD Met146Leu families from around the world resulted to be related and constitute a single kindred originating from Southern Italy before the 17th century. Phenotypic variability at onset is broad: 4 different clinical presentations may be recognized, 2 classic for AD (memory deficits and spatial and temporal disorientation), whereas the others are expressions of frontal impairment. The apathetic and dysexecutive subgroups could be related to orbital-medial prefrontal cortex and dorsolateral prefrontal cortex dysfunction. CONCLUSIONS: Genealogic and molecular findings provided evidence that the PSEN1 Met146Leu families from around the world analyzed in this study are related and represent a single kindred originating from Southern Italy. The marked phenotypic variability might reflect early involvement by the pathologic process of different cortical areas. Although the clinical phenotype is quite variable, the neuropathologic and biochemical characteristics of the lesions account for neurodegenerative processes unmistakably of Alzheimer nature.

Hawking radiation from ultrashort laser pulse filaments.

Event horizons of astrophysical black holes and gravitational analogues have been predicted to excite the quantum vacuum and give rise to the emission of quanta, known as Hawking radiation. We experimentally create such a gravitational analogue using ultrashort laser pulse filaments and our measurements demonstrate a spontaneous emission of photons that confirms theoretical predictions.

Association of the C677T polymorphism in the MTHFR gene with migraine: a meta-analysis.

There are conflicting data concerning the association between migraine and C677T polymorphism of the MTHFR gene. The C677T polymorphism reduces enzymatic capability by 50% and causes hyperhomocysteinaemia. We performed a meta-analysis of all published studies investigating the association between the MTHFR gene and migraine. Pooled odds ratios (OR) were estimated using random (RE) and fixed effects (FE) models. Among the overall 2961 migraineurs there was no significant difference compared with controls. Only in migraine with aura was the TT genotype associated with a higher risk of disease compared with the CC genotype [FE OR 1.30, 95% confidence interval (CI) 1.06, 1.58; RE OR 1.66, 95% CI 1.06, 2.59]. In the same subgroup a significant difference was observed in the comparison between TT and CT + CC genotypes (FE OR 1.32, 95% CI 1.10, 1.59; RE OR 1.63, 95% CI 1.10, 2.43). This study provides evidence for an association of the MTHFR gene only in migraine with aura.

Linear X-wave generation by means of cross-phase modulation in Kerr media.

We exploit cross-phase modulation by a strong driving pulse onto a weaker probe pulse at a different wavelength to induce the formation of an X wave possessing the typical nondispersive and nondiffractive propagation properties.

Finite-energy, accelerating Bessel pulses.

We numerically investigate the possibility to generate freely accelerating or decelerating pulses. In particular it is shown that acceleration along the propagation direction z may be obtained by a purely spatial modulation of an input Gaussian pulse in the form of finite-energy Bessel pulses with a cone angle that varies along the radial coordinate.We discuss simple practical implementations of such accelerating Bessel beams.

Generation and amplification of pulsed Bessel beams by seeding an optical parametric amplifier.

By using two very different seed pulses we demonstrate that the spatiotemporal gain properties of a chi(2) optical parametric amplifier can be exploited as an efficient conical reshaping mechanism leading to the generation and amplification of a pulsed Bessel beam.

Interleukin 6 gene polymorphisms are not associated with aneurysmal subarachnoid haemorrhage in an Italian population.

OBJECTIVE: Several lines of evidence indicate a role for inflammatory processes in the development of cerebral aneurysms. Recently, polymorphisms in the promoter region of the interleukin 6 (IL6) gene were shown to be associated with intracranial aneurysmal disease. The purpose of this study was to verify the association of two functionally active polymorphisms (-174 G>C and -572 G>C) in the promoter region of the IL6 gene with the risk and clinical features of aneurysmal subarachnoid haemorrhage (SAH) in an Italian population. METHODS: A total of 179 consecutive aneurysmal SAH patients and 156 healthy controls were involved in the study. Cases and controls were genotyped for the -174 G