Explore the vast range of titles available.

For the purpose of withstanding very high radiation doses, silicon pixel sensors with a 3D electrode geometry are being developed. Detectors of this kind are highly interesting for harch radiation environments such as expected in the High Luminosity LHC, but also for space physics and medical applications. In this paper, prototype sensors developed at SINTEF are presented and results from tests in a pion beam at CERN are given. These tests shows that these 3D sensors perform as expected with full efficiency at bias voltages between 5 and 15V.

The large-scale adoption of occupational exoskeletons (OEs) will only happen if clear evidence of effectiveness of the devices is available. Performing product-specific field validation studies would allow the stakeholders and decision-makers (e.g., employers, ergonomists, health, and safety departments) to assess OEs’ effectiveness in their specific work contexts and with experienced workers, who could further provide useful insights on practical issues related to exoskeleton daily use. This paper reviews present-day scientific methods for assessing the effectiveness of OEs in laboratory and field studies, and presents the vision of the authors on a roadmap that could lead to large-scale adoption of this technology. The analysis of the state-of-the-art shows methodological differences between laboratory and field studies. While the former are more extensively reported in scientific papers, they exhibit limited generalizability of the findings to real-world scenarios. On the contrary, field studies are limited in sample sizes and frequently focused only on subjective metrics. We propose a roadmap to promote large-scale knowledge-based adoption of OEs. It details that the analysis of the costs and benefits of this technology should be communicated to all stakeholders to facilitate informed decision making, so that each stakeholder can develop their specific role regarding this innovation. Large-scale field studies can help identify and monitor the possible side-effects related to exoskeleton use in real work situations, as well as provide a comprehensive scientific knowledge base to support the revision of ergonomics risk-assessment methods, safety standards and regulations, and the definition of guidelines and practices for the selection and use of OEs.

The Irpinia Fault, also known as the Monte Marzano Fault System, located in the Southern Apennines (Italy), is one of the most seismically active structures in the Mediterranean. It is the source of the 1980, Ms 6.9, multi-segment rupture earthquake that caused significant damage and nearly 3,000 casualties. Paleoseismological surveys indicate that this structure has generated at least four Mw ~ 7 surface-rupturing earthquakes in the past 2 ka. This paper presents a comprehensive, high-resolution geophysical investigation focused on the southernmost fault segment of the Monte Marzano Fault System, i.e., the Pantano-Ripa Rossa Fault, outcropping within the Pantano di San Gregorio Magno intramontane basin. The project, named TEst Site IRpinia fAult (TESIRA), was supported by the University of Napoli Federico II to study the near-surface structure of this intra-basin fault splay that repeatedly ruptured co-seismically in the past thousands of years. Our imaging approach included 2D and 3D electrical and seismic surveys, gravimetry, 3D FullWaver electrical tomography, drone-borne GPR and magnetic surveys, and CO 2 soil flux assessment across the surface rupture. This multidisciplinary investigation improved our understanding of the basin shallow structure, providing an image of a rather complex subsurface fault and basin geometry. Seismic data suggest that fault activity at the Pantano segment of MMFS is characterized by a near-surface cumulative displacement greater than previous estimations, calling into question earlier assumptions about the timing of its activation. Despite some challenges with our drone-mounted survey equipment, the integrated dataset provides a comprehensive and reliable image of the subsurface structure. This work demonstrates the utility of developing an integrated approach at high-resolution geophysical imaging and interpretation of fault zones with weak morphological expressions.

Huntington’s disease is caused by a pathologically long (>35) CAG repeat located in the first exon of the Huntingtin gene (HTT). While pathologically expanded CAG repeats are the focus of extensive investigations, non-pathogenic CAG tracts in protein-coding genes are less well characterized. Here, we investigated the function and evolution of the physiological CAG tract in the HTT gene. We show that the poly-glutamine (polyQ) tract encoded by CAGs in the huntingtin protein (HTT) is under purifying selection and subjected to stronger selective pressures than CAG-encoded polyQ tracts in other proteins. For natural selection to operate, the polyQ must perform a function. By combining genome-edited mouse embryonic stem cells and cell assays, we show that small variations in HTT polyQ lengths significantly correlate with cells’ neurogenic potential and with changes in the gene transcription network governing neuronal function. We conclude that during evolution natural selection promotes the conservation and purity of the CAG-encoded polyQ tract and that small increases in its physiological length influence neural functions of HTT. We propose that these changes in HTT polyQ length contribute to evolutionary fitness including potentially to the development of a more complex nervous system.

BackgroundPsoriatic arthritis (PsA) patients are often affected by numerous comorbidities. However, contrasting results have been reported with regard to the respiratory involvement in PsA patients. The aim of this study was to evaluate the presence of subclinical airway inflammation in non-smoking PsA patients compared to patients with only psoriasis using the fraction of exhaled nitric oxide (FeNO) as an indirect marker of airway inflammation.MethodsThe study included 164 non-smoking psoriatic patients (Psoriasis Area of Severity Index or PASI score > 10): 82 with and 82 without PsA, who underwent FeNO tests at different flow rates (30, 50, 100, 200 mL/s). PsA patients were evaluated with Disease Activity in PSoriatic Arthritis Score (DAPSA). Both study groups were compared in terms of FeNO values and its association with the PASI score. The correlations between the variables were evaluated by means of Pearson’s coefficient.ResultsPatient with PsA had higher levels of FeNO than those with psoriasis but without arthritis (at 30 mL/s, 71.09 ± 18.40 ppb vs 66.88 ± 19.12 ppb (NS); at 50 mL/s, 36.61 ± 9.30 ppb vs 30.88 ± 9.73 ppb (p < 0.001); at 100 mL/s, 19.09 ± 4.66 ppb vs 16.63 ± 4.90 ppb (p < 0.001); and at 200 mL/s, 10.88 ± 2.53 ppb vs 9.43 ± 2.55 ppb (p < 0.001), respectively). PASI score correlated to FeNO only in psoriatic patients without arthritis. However, CASPAR index correlated with FeNO (FeNO30: r = 0.81, p < 0.001; FeNO50: r = 0.84, p < 0.001; FeNO100: r = 0.71, p < 0.001; FeNO200: r = 0.58, p < 0.001). DAPSA was also correlated with FeNO to all flows (FeNO30: r = 0.43, p < 0.001; FeNO50: r = 0.33, p < 0.001; FeNO100: r = 0.34, p < 0.001; FeNO200: r = 0.25, p < 0.001).ConclusionsPsA patients seem to have more commonly subclinical airway inflammation than those with only psoriasis. Further studies are needed to replicate these findings.Key Points• Fraction of exhaled nitric oxide (FeNO) is a useful device to detect and monitor airway inflammation not only in asthma but also in systemic inflammatory diseases such as psoriatic arthritis and psoriasis.• Clinicians should be aware to check respiratory diseases in patients with psoriatic arthritis.

Canine vector-borne diseases (CVBDs) are caused by a range of pathogens transmitted to dogs by arthropods. The present study investigates Ehrlichia canis , Anaplasma spp., Borrelia burgdorferi sensu lato, and Dirofilaria immitis seroprevalences in hunting dogs from southern Italy. Dogs (no. 1335) were tested using a commercial in-clinic enzyme-linked immunosorbent assay kit. Odds ratios (ORs) were calculated by logistic regression analysis to identify risk factors. Overall, 138/1335 dogs (10.3%) were seroreactive to at least one CVBD pathogen. E. canis , Anaplasma spp., B. burgdorferi s.l., and D. immitis seroprevalences were 7.6, 4.4, 0.3, and 0.2%, respectively. E. canis and Anaplasma spp. co-exposures were found in 30 dogs (2.2%), compared with Anaplasma spp . and B. burgdorferi s.l. co-exposures in 2 dogs (0.1%). Adult age was a risk factor for E. canis (OR 2.35) seroreactivity whereas hunting fur-bearing animals for E. canis (OR 4.75) and Anaplasma spp. (OR 1.87), respectively. The historical presence of tick infestation was identified as a risk factor for positivity to E. canis (OR 2.08) and Anaplasma spp. (OR 2.15). Finally, larger dog pack size was significantly associated with E. canis (OR 1.85) and Anaplasma spp. (OR 2.42) exposures. The results of the present survey indicated that hunting dog populations are at relative risk of CVBDs in southern Italy. Further studies are needed to evaluate the role of hunting dogs in the epidemiology of vector-borne organisms due to sharing common environments with wild, sympatric animal populations.

It is generally accepted that adjacent guanine residues in DNA are the primary target for platinum antitumor drugs and that differences in the conformations of the Pt-DNA adducts can play a role in their antitumor activity. In this study, we investigated the effect of the carrier ligand cis-1,3-diaminocyclohexane (cis-1,3-DACH) upon formation, stability, and stereochemistry of the (cis-1,3-DACH)PtG2 and (cis-1,3-DACH)Pt(d(GpG)) adducts (G = 9-EthlyGuanine, guanosine, 5′- and 3′-guanosine monophosphate; d(GpG) = deoxyguanosil(3′-5′)deoxyguanosine). A peculiar feature of the cis-1,3-DACH carrier ligand is the steric bulk of the diamine, which is asymmetric with respect to the Pt-coordination plane. The (cis-1,3-DACH)Pt(5′GMP)2 and (cis-1,3-DACH)Pt(3′GMP)2 adducts show preference for the ΛHT and ∆HT conformations, respectively (HT stands for Head-to-Tail). Moreover, the increased intensity of the circular dichroism signals in the cis-1,3-DACH derivatives with respect to the analogous cis-(NH3)2 species could be a consequence of the greater bite angle of the cis-1,3-DACH carrier ligand with respect to cis-(NH3)2. Finally, the (cis-1,3-DACH)Pt(d(GpG)) adduct is present in two isomeric forms, each one giving a pair of H8 resonances linked by a NOE cross peak. The two isomers were formed in comparable amounts and had a dominance of the HH conformer but with some contribution of the ΔHT conformer which is related to the HH conformer by having the 3′-G base flipped with respect to the 5′-G residue.

Fasting during the month of Ramadan consists of alternate abstinence and re-feeding periods (circadian or intermittent fasting). Nothing is currently known on the impact of this kind of fasting on psoriasis. A sample of 108 moderate-to-severe plaque psoriasis patients (aged 42.84 ± 13.61 years, 62 males, 46 females) volunteered to take part in the study. A significant decrease in the “Psoriasis Area and Severity Index” (PASI) score after the Ramadan fasting (mean difference = −0.89 ± 1.21, p < 0.0001) was found. At the multivariate regression, the use of cyclosporine (p = 0.0003), interleukin-17 or IL-17 blockers (p < 0.0001), and tumor necrosis factor or TNF blockers (p = 0.0107) was independently associated with a low PASI score, while the use of apremilast (p = 0.0009), and phototherapy (p = 0.0015) was associated with a high PASI score before the Ramadan fasting. Similarly, the consumption of cyclosporine (p < 0.0001), IL-17 blockers (p < 0.0001), mammalian target of rapamycin or mTOR inhibitors (p = 0.0081), and TNF blockers (p = 0.0017) predicted a low PASI score after the Ramadan fasting. By contrast, narrow band ultraviolet light B or NB-UVB (p = 0.0015) was associated with a high PASI score after Ramadan fasting. Disease duration (p = 0.0078), use of apremilast (p = 0.0005), and of mTOR inhibitors (p = 0.0034) were independent predictors of the reduction in the PASI score after the Ramadan fasting. These findings reflect the influence of dieting strategy, the biological clock, and circadian rhythm on the treatment of plaque psoriasis.

Two new Pt(II)-pyrophosphato complexes containing the carrier ligands cis-1,3-diaminocyclohexane (cis-1,3-DACH) and trans-1,2-diamine-4-cyclohexene (1,2-DACHEX), variants of the 1R,2R-diaminocyclohexane ligand present in the clinically used Pt-drug oxaliplatin, have been synthesized with the aim of developing new potential antitumor drugs with high bone tropism. The complexes are more stable at physiological pH than in acid conditions, with Na2[Pt(pyrophosphato)(cis-1,3-DACH)] (1) slightly more stable than [Pt(dihydrogenpyrophosphato)(1,2-DACHEX)] (2). The greater reactivity at acidic pH ensures a greater efficacy at the tumor site. Preliminary NMR studies indicate that 1 and 2 react slowly with 5’-GMP (used as a model of nucleic acids), releasing the pyrophosphate ligand and affording the bis 5’-GMP adduct. In vitro cytotoxicity assays performed against a panel of four human cancer cell lines have shown that both compounds are more active than oxaliplatin. Flow cytometry studies on HCT116 cells showed that the pyrophosphato compounds with the non-classical 1,3- and 1,4-diaminocyclohexane ligands (1 and 4) are the most capable to induce cells’ death by apoptosis and necrosis.