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Objective Unilateral hypoglossal nerve stimulation (HGNS) to treat obstructive sleep apnea involves implantation of a pulse generator, a respiratory sensing lead, and a stimulation lead. Complications may arise related to all components. Previous studies have presented the overall incidence of reported adverse events. The objective of this study was to provide an updated report of complications from the Food and Drug Administration's Manufacturer and User Facility Device Experience (MAUDE) database, with a focus on the respiratory sensing lead, and propose a care algorithm with two cases of sensing lead migration. Study Design Retrospective cross‐sectional study, case report. Setting Tertiary care center. Methods The MAUDE database was queried for events related to the HGNS respiratory sensing lead from January 1, 2000, to December 1, 2022. Primary outcomes were respiratory lead migration resulting in pneumothorax or need for revision surgery/explantation. Results In total, 151 out of 765 HGNS adverse events were related to the respiratory sensing lead, and of those, 75 were related to lead migration. There were seven events related to migration of the sensing lead into the pleural space, of which six cases underwent revision surgery (<1% of adverse events reported related to HGNS). Two cases noted pneumothorax due to sensing lead migration. We report two cases of sensing lead migration at our institution. Migration was demonstrated with serial imaging. These cases highlight the potential need for preoperative or intraoperative chest tube placement, based on the extent of migration, complications, and complexity. Conclusion Migration of the respiratory sensing lead is a rare event with multidisciplinary surgical planning considerations.

Children and adolescents with haematological malignancies (PedHM) are characterized by a severe loss of exercise ability during cancer treatment, lasting throughout their lives once healed and impacting their social inclusion prospects. The investigation of the effect of a precision-based exercise program on the connections between systems of the body in PedHM patients is the new frontier in clinical exercise physiology. This study is aimed at evaluating the effects of 11 weeks (3 times weekly) of combined training (cardiorespiratory, resistance, balance and flexibility) on the exercise intolerance in PedHM patients. Two-hundred twenty-six PedHM patients were recruited (47% F). High or medium frequency participation (HAd and MAd) was considered when a participant joined; > 65% or between 30% and < 64% of training sessions, respectively. The “up and down stairs'' test (TUDS), “6 min walking” test (6MWT), the “5 Repetition Maximum strength” leg extension and arm lateral raise test (5RM-LE and 5RM-ALR), flexibility (stand and reach), and balance (stabilometry), were performed and evaluated before and after training. The TUDS, the 5RM-LE and 5RM-ALR, and the flexibility exercises showed an increase in HAd and MAd groups ( P  <  0.05 ), while the 6MWT and balance tests showed improvement only in HAd group ( P  <  0.0001 ). These results support the ever-growing theory that, in the case of the treatment of PedHM, ‘exercise is medicine’ and it has the potential to increase the patient’s chances of social inclusion.

ProNGF, the precursor of mature nerve growth factor (NGF), is the most abundant form of NGF in the brain. ProNGF and mature NGF differ significantly in their receptor interaction properties and in their bioactivity. ProNGF increases markedly in the cortex of Alzheimer’s disease (AD) brains and proNGF\\NGF imbalance has been postulated to play a role in neurodegeneration. However, a direct proof for a causal link between increased proNGF and AD neurodegeneration is lacking. In order to evaluate the consequences of increased levels of proNGF in the postnatal brain, transgenic mice expressing a furin cleavage-resistant form of proNGF, under the control of the neuron-specific mouse Thy1.2 promoter, were derived and characterized. Different transgenic lines displayed a phenotypic gradient of neurodegenerative severity features. We focused the analysis on the two lines TgproNGF#3 and TgproNGF#72, which shared learning and memory impairments in behavioral tests, cholinergic deficit and increased A β -peptide immunoreactivity. In addition, TgproNGF#3 mice developed A β oligomer immunoreactivity, as well as late diffuse astrocytosis. Both TgproNGF lines also display electrophysiological alterations related to spontaneous epileptic-like events. The results provide direct evidence that alterations in the proNGF/NGF balance in the adult brain can be an upstream driver of neurodegeneration, contributing to a circular loop linking alterations of proNGF/NGF equilibrium to excitatory/inhibitory synaptic imbalance and amyloid precursor protein (APP) dysmetabolism.

In this work we report the ongoing characterization of the Sos Enattos former mine (Sardinia, Italy), one of the two candidate sites for the Einstein Telescope (ET), the European third-generation underground interferometric detector of Gravitational Waves. The Sos Enattos site lies on a crystalline basement, made of rocks with good geomechanical properties, characterized by negligible groundwater. In addition, the site has a very low seismic background noise due to the absence of active tectonics involving Sardinia. Finally, the area has a low population density, resulting in a reduced anthropic noise even at the ground level. This location was already studied in 2012-2014 as a promising site for an underground detector. More recently, in March 2019, we deployed a new network of surface and underground seismometers at the site, that is currently monitoring the local seismic noise. Most of the energy carried by the seismic waves is due to the microseisms below 1 Hz, showing a significant correlation with the waves of the west Mediterranean sea. Above 1 Hz the seismic noise in the underground levels of the mine approaches the Peterson's low noise model. Exploiting mine blasting works into the former mine, we were also able to perform active seismic measurements to evaluate the seismic waves propagation across the area. In conclusion we also give a first assessment about the acoustic and magnetic noise in this underground site.

Third-generation gravitational wave observatories will extend the lower frequency limit of the observation band toward 2 Hz, where new sources of gravitational waves, in particular intermediate-mass black holes (IMBH), will be detected. In this frequency region, seismic noise will play an important role, mainly through the so-called Newtonian noise, i.e., the gravity-mediated coupling between ground motion and test mass displacements. The signal lifetime of such sources in the detector is of the order of tens of seconds. In order to determine whether a candidate site to host the Einstein Telescope observatory is particularly suitable to observe such sources, it is necessary to estimate the probability distributions that, in the characteristic time scale of the signal, the sensitivity of the detector is not perturbed by Newtonian noise. In this paper, a first analysis is presented, focused on the Sos Enattos site (Sardinia, Italy), a candidate to host the Einstein Telescope. Starting from a long data set of seismic noise, this distribution is evaluated considering both the presently designed triangular ET configuration and also the classical ”L” configuration.

The stir bar sorptive extraction (SBSE) technique was used to determine volatile constituents in two peach cultivars, one yellow-fleshed (cv. Spring Lady) and one white-fleshed (cv. Regina Bianca). For both cultivars four distinct experimental samples were considered, each formed by fruits obtained with four different cultivation practices. In order to investigate the effects of cold storage on the volatile profile, on all peach experimental samples changes in aroma compounds after 1 and 2 weeks of storage at 1°C, plus 1 day at ambient temperature, were monitored; moreover, only on the four experimental samples from cv. Regina Bianca, the effect of a prestorage hot water treatment (46°C for 25 min) was also evaluated. On the isolate obtained by SBSE, 24 compounds were identified and quantified by GC-MS: saturated and unsaturated lactones, aldehydes, C 13 norisoprenoids, monoterpenes, alcohols and esters. The profile of the white-fleshed cultivar was characterised by a higher level of C 13 norisoprenoids, and, in particular, of 8,9-dehydrotheaspirone. In all experimental samples after 1 week of storage, plus 1 day at ambient temperature, a marked increase (on average by 89%) in total lactones was observed. This increase was due to a noticeable accumulation of saturated lactones with longer side chains (γ- and δ-decalactone) and unsaturated lactones (( Z )-dec-7-en-5-olide and γ-jasmolactone). Peaches analysed after 2 weeks of storage showed total lactone levels close to those detected in the samples at harvest, suggesting that increasing storage times reduced fruit ability to accumulate these character impact compounds of peach aroma. A similar effect of cold storage, although less marked, was also observed on C 13 norisoprenoid fraction, but only on cv. Regina Bianca. On the other hand, we did not find univocal effects of cold storage on C 6 aldehydes, whereas linalool, detected only in samples of cv. Spring Lady at harvest, disappeared quickly during the first days of storage. In samples of cv. Regina Bianca peaches subjected to hot water treatment, after 1 week of storage, lactone level was significantly reduced in comparison with untreated fruits, denoting a possible inhibition effect on lactone accumulation and on aroma development.

A correction to this paper has been published: https://doi.org/10.1140/epjp/s13360-021-01561-2

WEB-2086 – an antagonist of platelet-activating factor receptor (PAFR) with known anti-inflammatory, antiangiogenic and antileukaemic properties – also proved to inhibit the proliferation in human solid tumour cell lines of different histology, and with much higher efficacy than in normal fibroblasts. A detailed analysis of WEB-2086 anticancer activity was then performed focusing on breast adenocarcinoma MCF-7 and MDA-MB-231 cells. WEB-2086-treated cells, either expressing (MCF-7) or unexpressing (MDA-MB-231) the oestrogen receptor (ER) α , underwent a dose-dependent growth arrest (IC 50 =0.65±0.09 and 0.41±0.07 m M , respectively) and accumulation in G 0 –G 1 phase. WEB-2086 also induced morphological and functional changes typical of mature mammary phenotype including (i) cell enlargement and massive neutral lipid deposition (best accomplished in MCF-7 cells); (ii) decrease in motility and active cathepsin D levels (mainly observed in highly invasive MDA-MB-231 cells). The expression of ER α was neither increased nor reactivated in treated MCF-7 or MDA-MB-231 cells, respectively. WEB-2086-induced differentiation in breast cancer cells involved the upregulation of PTEN, a key tumour suppressor protein opposing tumorigenesis, and was apparently independent of p53, PAFR, peripheral benzodiazepine receptor and ER α status. Overall, WEB-2086 can be proposed as an effective antiproliferative and differentiative agent with interesting translational opportunities to treat breast cancers in support to conventional chemotherapy.

Reduced glutathione (GSH) is present in millimolar concentrations in mammalian cells. It is involved in many cellular functions such as detoxification, amino acid transport, production of coenzymes, and the recycling of vitamins E and C. GSH acts as a redox buffer to preserve the reduced intracellular environment. Decreased glutathione levels have been found in numerous diseases such as cancer, viral infections, and immune dysfunctions. Many antioxidant molecules, such as GSH and N-acetylcysteine (NAC), have been demonstrated to inhibit in vitro and in vivo viral replication through different mechanisms of action. Accumulating evidence suggests that intracellular GSH levels in antigen-presenting cells such as macrophages, influence the Th1/Th2 cytokine response pattern, and more precisely, GSH depletion inhibits Th1-associated cytokine production and/or favours Th2 associated responses. It is known that GSH is not transported to most cells and tissues in a free form. Therefore, a number of different approaches have been developed in the last years to circumvent this problem. This review discusses the capacity of some new molecules with potent pro- GSH effects either to exert significant antiviral activity or to augment GSH intracellular content in macrophages to generate and maintain the appropriate Th1/Th2 balance. The observations reported herein show that pro-GSH molecules represent new therapeutic agents to treat antiviral infections and Th2-mediated diseases such as allergic disorders and AIDS.

Changes in antioxidants (ascorbic acid, phenolic compounds and carotenoids) and in taste-related compounds (sugars and organic acids) content were monitored in fresh-cut red sweet peppers (Capsicum annuum L., local ecotype “Peperone Cornetto di Pontecorvo”) during 9 days of cold storage. Pepper slices were placed in polystyrene trays, wrapped with a polyvinyl chloride film, and stored at 4 °C or at 8 °C; besides, to evaluate the effect of a prestorage hot water treatment, half of the slices were subjected to a dipping treatment in water at 53 °C for 4 min, before packaging and storage. During storage limited changes in O₂ and CO₂ concentrations were observed within all packages. Storage temperature strongly affected weight loss: at the end of the storage time it was <3 and >10% in fruits stored at 4 and 8 °C, respectively. Sugars (glucose and fructose) content showed a significant increase (+11%) only in fruits stored at 8 °C; this change was due to a concentration effect associated to water loss. A higher increase (+23 and +17% in fruits stored at 8 and 4 °C) was observed in organic acids (citric and malic) content. Minimal processing and storage produced only a quite limited degradation of ascorbic acid. Both hydroxycinnamic acid derivatives and flavonoids accumulated in fruits stored at 8 °C (and not heat treated), whereas at 4 °C phenolics accumulation appeared to be partially inhibited. All the main carotenoids (capsanthin, cucurbitaxanthin A, zeaxanthin, β-carotene and β-cryptoxanthin) markedly accumulated in fruits stored at 8 °C (not heat treated), and showed a general decrease at 4 °C. Hot water treatment did seem to affect organic acids metabolism, though it did not promote ascorbic acid degradation. In addition, it inhibited both phenolics and carotenoid accumulation in fruits stored at 8 °C.