IGF-II promotes neuroprotection and neuroplasticity recovery in a long-lasting model of oxidative damage induced by glucocorticoids

Insulin-like growth factor-II (IGF-II) is a naturally occurring hormone that exerts neurotrophic and neuroprotective properties in a wide range of neurodegenerative diseases and ageing. Accumulating evidence suggests that the effects of IGF-II in the brain may be explained by its binding to the specific transmembrane receptor, IGFII/M6P receptor (IGF-IIR). However, relatively little is known regarding the role of IGF-II through IGF-IIR in neuroprotection. Here, using adult cortical neuronal cultures, we investigated whether IGF-II exhibits long-term antioxidant effects and neuroprotection at the synaptic level after oxidative damage induced by high and transient levels of corticosterone (CORT). Furthermore, the involvement of the IGF-IIR was also studied to elucidate its role in the neuroprotective actions of IGF-II. We found that neurons treated with IGF-II after CORT incubation showed reduced oxidative stress damage and recovered antioxidant status (normalized total antioxidant status, lipid hydroperoxides and NAD(P) H:quinone oxidoreductase activity). Similar results were obtained when mitochondria function was analysed (cytochrome c oxidase activity, mitochondrial membrane potential and subcellular mitochondrial distribution). Furthermore, neuronal impairment and degeneration were also assessed (synaptophysin and PSD-95 expression, presynaptic function and FluoroJade B® stain). IGF-II was also able to recover the long-lasting neuronal cell damage. Finally, the effects of IGF-II were not blocked by an IGF-IR antagonist, suggesting the involvement of IGF-IIR. Altogether these results suggest that, in or model, IGF-II through IGF-IIR is able to revert the oxidative damage induced by CORT. In accordance with the neuroprotective role of the IGF-II/IGF-IIR reported in our study, pharmacotherapy approaches targeting this pathway may be useful for the treatment of diseases associated with cognitive deficits (i.e., neurodegenerative disorders, depression, etc.)

High resting energy expenditure, less fat-free mass, and less muscle strength in HIV-infected children: a matched, cross-sectional study

Background and aimsMany improvements have been made in the treatment of human immunodeficiency virus (HIV) in pediatric patients; however, challenges remain in terms of achieving normal growth, body composition, and metabolism during treatment, etc. Current nutritional recommendations are based on studies performed in adults, with limited data on the HIV-infected pediatric population. Therefore, this study aimed to compare the resting energy expenditure (REE) of asymptomatic HIV-infected pediatric patients with healthy counterparts and to compare body composition, dietary intake, and physical activity between the two groups.MethodsThis was a cross-sectional study of asymptomatic HIV-infected children who were receiving antiretroviral therapy; the infected group was compared with the uninfected group, matched by age (± 6 months), sex, and body mass index (± 0.5 z-score). Participants were recruited between 2021 and 2022, as outpatients. In both groups, REE was determined by indirect calorimetry and body composition by bioelectrical impedance analysis and hand strength, measured using a hydraulic hand dynamometer.ResultsSeventy-eight participants were enrolled, where n = 39 HIV-infected children and n = 39 controls, with a mean age of 11.6 ± 3.4 years old. REE was significantly higher in the HIV group (1254.4 ± 334.7 kcal/day vs. 1124.7 ± 321 kcal/day, p = 0.013) than in the control group. Fat-free mass (FFM) was lower in the HIV group (28.2 ± 10.5 kg vs. 32 ± 11.2 kg, p = 0.001); this trend continued when the index skeletal muscle was evaluated (7.2 ± 1.2 vs. 7.6 ± 1.5, p = 0.04). The strength of the dominant hand was also lower in the HIV group (12 (8–18) kg vs. 20 (10.5–26) kg, p < 0.0001).ConclusionsChildren with asymptomatic HIV infection have higher REE than their uninfected peers. They also present decreased FFM, skeletal muscle mass index, and muscle strength. These parameters should be considered during nutritional assessment in this population to have a favorable impact on nutritional status and growth

Search for a vector-like quark T′ → tH via the diphoton decay mode of the Higgs boson in proton-proton collisions at s \sqrt{s} = 13 TeV

A search for the electroweak production of a vector-like quark T′, decaying to a top quark and a Higgs boson is presented. The search is based on a sample of proton-proton collision events recorded at the LHC at = 13 TeV, corresponding to an integrated luminosity of 138 fb−1. This is the first T′ search that exploits the Higgs boson decay to a pair of photons. For narrow isospin singlet T′ states with masses up to 1.1 TeV, the excellent diphoton invariant mass resolution of 1–2% results in an increased sensitivity compared to previous searches based on the same production mechanism. The electroweak production of a T′ quark with mass up to 960 GeV is excluded at 95% confidence level, assuming a coupling strength κT = 0.25 and a relative decay width Γ/MT′ < 5%

Search for new physics in multijet events with at least one photon and large missing transverse momentum in proton-proton collisions at 13 TeV

A search for new physics in final states consisting of at least one photon, multiple jets, and large missing transverse momentum is presented, using proton-proton collision events at a center-of-mass energy of 13 TeV. The data correspond to an integrated luminosity of 137 fb−1, recorded by the CMS experiment at the CERN LHC from 2016 to 2018. The events are divided into mutually exclusive bins characterized by the missing transverse momentum, the number of jets, the number of b-tagged jets, and jets consistent with the presence of hadronically decaying W, Z, or Higgs bosons. The observed data are found to be consistent with the prediction from standard model processes. The results are interpreted in the context of simplified models of pair production of supersymmetric particles via strong and electroweak interactions. Depending on the details of the signal models, gluinos and squarks of masses up to 2.35 and 1.43 TeV, respectively, and electroweakinos of masses up to 1.23 TeV are excluded at 95% confidence level

Observation of the Rare Decay of the η Meson to Four Muons

A search for the rare η→μ+μ−μ+μ− double-Dalitz decay is performed using a sample of proton-proton collisions, collected by the CMS experiment at the CERN LHC with high-rate muon triggers during 2017 and 2018 and corresponding to an integrated luminosity of 101  fb−1. A signal having a statistical significance well in excess of 5 standard deviations is observed. Using the η→μ+μ− decay as normalization, the branching fraction B(η→μ+μ−μ+μ−)=[5.0±0.8(stat)±0.7(syst)±0.7(B2μ)]×10−9 is measured, where the last term is the uncertainty in the normalization channel branching fraction. This work achieves an improved precision of over 5 orders of magnitude compared to previous results, leading to the first measurement of this branching fraction, which is found to agree with theoretical predictions

Measurement of the Higgs boson inclusive and differential fiducial production cross sections in the diphoton decay channel with pp collisions at s \sqrt{s} = 13 TeV

The measurements of the inclusive and differential fiducial cross sections of the Higgs boson decaying to a pair of photons are presented. The analysis is performed using proton-proton collisions data recorded with the CMS detector at the LHC at a centre-of-mass energy of 13 TeV and corresponding to an integrated luminosity of 137 fb$^{−1}$. The inclusive fiducial cross section is measured to be $σ_{fid}$=73.4$^{+5.4}_{−5.3}$(stat)$^{+2.4}_{−2.2}$(syst) fb, in agreement with the standard model expectation of 75.4 ± 4.1 fb. The measurements are also performed in fiducial regions targeting different production modes and as function of several observables describing the diphoton system, the number of additional jets present in the event, and other kinematic observables. Two double differential measurements are performed. No significant deviations from the standard model expectations are observed

Search for Higgs Boson Decay to a Charm Quark-Antiquark Pair in Proton-Proton Collisions at √s = 13 TeV

A search for the standard model Higgs boson decaying to a charm quark-antiquark pair, H→c¯c, produced in association with a leptonically decaying V (W or Z) boson is presented. The search is performed with proton-proton collisions at √s=13  TeV collected by the CMS experiment, corresponding to an integrated luminosity of 138  fb−1. Novel charm jet identification and analysis methods using machine learning techniques are employed. The analysis is validated by searching for Z→c¯c in VZ events, leading to its first observation at a hadron collider with a significance of 5.7 standard deviations. The observed (expected) upper limit on σ(VH)B(H→c¯c) is 0.94 (0.50+0.22−0.15)pb at 95% confidence level (C.L.), corresponding to 14 (7.6+3.4−2.3) times the standard model prediction. For the Higgs-charm Yukawa coupling modifier, κc, the observed (expected) 95% C.L. interval is 1.1<|κc|<5.5 (|κc|<3.4), the most stringent constraint to date