S-nitrosylation of NF-kB p65 inhibits TSH-induced Na+/I- symporter expression

Nitric oxide (NO) is a ubiquitous signaling molecule involved in a wide variety of cellular physiological processes. In thyroid cells, NO-synthase III-endogenously produced NO reduces thyrotropin (TSH)-stimulated thyroid specific gene expression, suggesting a potential autocrine role of NO in modulating thyroid function. Further studies indicate that NO induces thyroid dedifferentiation, as NO donors repress TSH-stimulated I- uptake. Here, we investigated the molecular mechanism underlying the NO inhibited Na+/I- Symporter (NIS)-mediated I- uptake in thyroid cells. We showed that NO donors reduce I- uptake in a concentration-dependent manner, which correlates with decreased NIS protein expression. NO-reduced I- uptake results from transcriptional repression of NIS gene rather than post-translational modifications reducing functional NIS expression at the plasma membrane. We observed that NO donors repress TSH-induced NIS gene expression by reducing the transcriptional activity of the NF-κB subunit p65. NO-promoted p65 S-nitrosylation reduces p65-mediated transactivation of the NIS promoter in response to TSH stimulation. Overall, our data are consistent with the notion that NO plays a role as an inhibitory signal to counterbalance TSH-stimulated NF-κB activation, thus modulating thyroid hormone biosynthesis.Fil: Nicola, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Peyret, Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Nazar, Magalí. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Bioquímica Clínica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Romero, Jorge Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; ArgentinaFil: Lucero, Ariel Maximiliano. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Montesinos, Maria del Mar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Bocco, Jose Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Pellizas, Claudia Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Masini, Ana María. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Bioquímica Clínica; Argentin

The global burden of cancer attributable to risk factors, 2010-19 : a systematic analysis for the Global Burden of Disease Study 2019

Background Understanding the magnitude of cancer burden attributable to potentially modifiable risk factors is crucial for development of effective prevention and mitigation strategies. We analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 to inform cancer control planning efforts globally. Methods The GBD 2019 comparative risk assessment framework was used to estimate cancer burden attributable to behavioural, environmental and occupational, and metabolic risk factors. A total of 82 risk-outcome pairs were included on the basis of the World Cancer Research Fund criteria. Estimated cancer deaths and disability-adjusted life-years (DALYs) in 2019 and change in these measures between 2010 and 2019 are presented. Findings Globally, in 2019, the risk factors included in this analysis accounted for 4.45 million (95% uncertainty interval 4.01-4.94) deaths and 105 million (95.0-116) DALYs for both sexes combined, representing 44.4% (41.3-48.4) of all cancer deaths and 42.0% (39.1-45.6) of all DALYs. There were 2.88 million (2.60-3.18) risk-attributable cancer deaths in males (50.6% [47.8-54.1] of all male cancer deaths) and 1.58 million (1.36-1.84) risk-attributable cancer deaths in females (36.3% [32.5-41.3] of all female cancer deaths). The leading risk factors at the most detailed level globally for risk-attributable cancer deaths and DALYs in 2019 for both sexes combined were smoking, followed by alcohol use and high BMI. Risk-attributable cancer burden varied by world region and Socio-demographic Index (SDI), with smoking, unsafe sex, and alcohol use being the three leading risk factors for risk-attributable cancer DALYs in low SDI locations in 2019, whereas DALYs in high SDI locations mirrored the top three global risk factor rankings. From 2010 to 2019, global risk-attributable cancer deaths increased by 20.4% (12.6-28.4) and DALYs by 16.8% (8.8-25.0), with the greatest percentage increase in metabolic risks (34.7% [27.9-42.8] and 33.3% [25.8-42.0]). Interpretation The leading risk factors contributing to global cancer burden in 2019 were behavioural, whereas metabolic risk factors saw the largest increases between 2010 and 2019. Reducing exposure to these modifiable risk factors would decrease cancer mortality and DALY rates worldwide, and policies should be tailored appropriately to local cancer risk factor burden. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.Peer reviewe

Anestesia neuroaxial en trabajo de parto y cesárea en pacientes con antecedentes de mielomeningocele operado

Los desórdenes del desarrollo del tubo neural son el segundo mayor grupo de malformaciones congénitas conocidas y con una incidencia de 1/1000 nacidos vivos. El meningomielocele es una de las malformaciones más frecuentes. Se define como una falla en el cierre del tubo neural con herniación de meninges y elementos neurales. El embarazo en estas pacientes es complicado por las deformidades físicas y complicaciones neurológicas secundarias, pudiendo dificultar la técnica anestésica neuroaxial en el trabajo de parto y operación cesárea. Existen escasos reportes de pacientes con meningomielocele en trabajo de parto y analgesia neuroaxial. Presentamos una revisión de esta patología y las técnicas anestésicas utilizadas en el trabajo de parto y operación cesárea de pacientes con antecedente de meningomielocele, basados en un caso clínico del cual participamos

Sternal torsion in pectus excavatum is related to cardiac compression and chest malformation indexes

Background/purpose: The role of sternal torsion (ST) in patients with pectus excavatum (PEX) is unknown. We evaluated the relationship between ST and both chest malformation and cardiac compression (CC) indexes. Methods: We included consecutive patients with PEX who underwent chest computed tomography and cardiac magnetic resonance (CMR) to define surgical candidacy. Malformation indexes included the Haller index (HI), correction index (CI), and ST. CC and the tricuspid to mitral annulus width ratio were evaluated using CMR. Results: One-hundred and sixteen patients were included, with a mean HI of 5.8 ± 3.6 and a mean CI of 35.8 ± 18.0%. ST was significantly related to malformation indexes, being patients with absence of ST those showing the lowest HI (p = 0.048) and CI (p = 0.002). Right-sided ST was significantly related to the CC classification (p = 0.0001), and the tricuspid/mitral annulus width ratio was significantly lower among these patients (absence 0.98 ± 0.15, left-sided 0.91 ± 0.10, right-sided 0.80 ± 0.15, p < 0.0001). A significant inverse relationship between ST degrees and the tricuspid/mitral ratio was also identified (r = -0.47, p < 0.0001). Conclusions: We identified a significant relationship between ST and both chest malformation and CC indexes; the absence of ST being identified as a marker of an overall more benign phenotype.Fil: Capunay, Carlos. No especifíca;Fil: Martínez Ferro, Marcelo. No especifíca;Fil: Carrascosa, Patricia. No especifíca;Fil: Bellia Munzon, Gaston. No especifíca;Fil: Deviggiano, Alejandro. No especifíca;Fil: Nazar, Maximiliano. No especifíca;Fil: Martinez, Jorge Luis. No especifíca;Fil: Rodriguez Granillo, Gaston Alfredo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas; Argentin

Impact of pectus excavatum on cardiac morphology and function according to the site of maximum compression: effect of physical exertion and respiratory cycle

Aims: Previous studies have demonstrated diverse cardiac manifestations in patients with pectus excavatum (PEX), although mostly addressing morphological or physiological impact as separate findings. Using multimodality imaging, we evaluated the impact of PEX on cardiac morphology and function according to the site of maximum compression, and the effect of exertion and breathing. Methods and results: All patients underwent chest computed tomography, cardiac magnetic resonance (CMR), and stress echocardiography (echo) in order to establish surgical candidacy. We evaluated diastolic function and trans-tricuspid gradient during stress (echo); and systolic function and respiratory-related septal wall motion abnormalities (CMR). Patients were classified according to the site of cardiac compression as type 0 (without cardiac compression); type 1 (right ventricle); and type 2 [right ventricle and atrioventricular (AV) groove]. Fifty-nine patients underwent multimodality imaging, with a mean age of 19.5 ± 5.9 years. Compared with a sex and age matched control group, peak exercise capacity was lower in patients with PEX (8.4 ± 2.0 METs vs. 15.1 ± 4.6 METs, P < 0.0001). At stress, significant differences were found between groups regarding left ventricular E/A (P = 0.004) and e/a ratio (P = 0.005), right ventricular E/A ratio (P = 0.03), and trans-tricuspid gradient (P = 0.001). At CMR, only 9 (15%) patients with PEX had normal septal motion, whereas 17 (29%) had septal flattening during inspiration. Septal motion abnormalities were significantly related to the cardiac compression classification (P < 0.0001). Conclusions: The present study demonstrated that patients with PEX, particularly those with compression affecting the right ventricle and AV groove, manifest diverse cardiac abnormalities that are mostly related to exertion, inspiration, and diastolic function.Fil: Rodriguez Granillo, Gaston Alfredo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Alberto C. Taquini de Investigaciones en Medicina Traslacional - Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas "Prof. Dr. Alberto C. Taquini". Instituto Alberto C. Taquini de Investigaciones en Medicina Traslacional; ArgentinaFil: Raggio, Ignacio M.. No especifíca;Fil: Deviggiano, Alejandro. No especifíca;Fil: Bellia Munzon, Gastón. No especifíca;Fil: Capunay, Carlos. No especifíca;Fil: Nazar, Maximiliano. No especifíca;Fil: Martinez, Jorge Luis. No especifíca;Fil: Carrascosa, Patricia. No especifíca;Fil: Martínez Ferro, Marcelo. No especifíca

The global burden of cancer attributable to risk factors, 2010-19: a systematic analysis for the Global Burden of Disease Study 2019

Background Understanding the magnitude of cancer burden attributable to potentially modifiable risk factors is crucial for development of effective prevention and mitigation strategies. We analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 to inform cancer control planning efforts globally. Methods The GBD 2019 comparative risk assessment framework was used to estimate cancer burden attributable to behavioural, environmental and occupational, and metabolic risk factors. A total of 82 risk-outcome pairs were included on the basis of the World Cancer Research Fund criteria. Estimated cancer deaths and disability-adjusted life-years (DALYs) in 2019 and change in these measures between 2010 and 2019 are presented. Findings Globally, in 2019, the risk factors included in this analysis accounted for 4.45 million (95% uncertainty interval 4.01-4.94) deaths and 105 million (95.0-116) DALYs for both sexes combined, representing 44.4% (41.3-48.4) of all cancer deaths and 42.0% (39.1-45.6) of all DALYs. There were 2.88 million (2.60-3.18) risk-attributable cancer deaths in males (50.6% 47.8-54.1] of all male cancer deaths) and 1.58 million (1.36-1.84) risk-attributable cancer deaths in females (36.3% 32.5-41.3] of all female cancer deaths). The leading risk factors at the most detailed level globally for risk-attributable cancer deaths and DALYs in 2019 for both sexes combined were smoking, followed by alcohol use and high BMI. Risk-attributable cancer burden varied by world region and Socio-demographic Index (SDI), with smoking, unsafe sex, and alcohol use being the three leading risk factors for risk-attributable cancer DALYs in low SDI locations in 2019, whereas DALYs in high SDI locations mirrored the top three global risk factor rankings. From 2010 to 2019, global risk-attributable cancer deaths increased by 20.4% (12.6-28.4) and DALYs by 16.8% (8.8-25.0), with the greatest percentage increase in metabolic risks (34.7% 27.9-42.8] and 33.3% 25.8-42.0]). Interpretation The leading risk factors contributing to global cancer burden in 2019 were behavioural, whereas metabolic risk factors saw the largest increases between 2010 and 2019. Reducing exposure to these modifiable risk factors would decrease cancer mortality and DALY rates worldwide, and policies should be tailored appropriately to local cancer risk factor burden. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license

Observation of medium-induced yield enhancement and acoplanarity broadening of low-pTp_\mathrm{T} jets from measurements in pp and central Pb−-Pb collisions at sNN=5.02\sqrt{s_{\rm NN}}=5.02 TeV

International audienceThe ALICE Collaboration reports the measurement of semi-inclusive distributions of charged-particle jets recoiling from a high transverse momentum (high $p_{\rm T}$) hadron trigger in proton$-$proton and central Pb$-$Pb collisions at $\sqrt{s_{\rm NN}} = 5.02$ TeV. A data-driven statistical method is used to mitigate the large uncorrelated background in central Pb$-$Pb collisions. Recoil jet distributions are reported for jet resolution parameter $R=0.2$, 0.4, and 0.5 in the range $7 < p_{\rm T,jet} < 140$ GeV$/c$ and trigger$-$recoil jet azimuthal separation $\pi/2 < \Delta\varphi < \pi$. The measurements exhibit a marked medium-induced jet yield enhancement at low $p_{\rm T}$ and at large azimuthal deviation from $\Delta\varphi\sim\pi$. The enhancement is characterized by its dependence on $\Delta\varphi$, which has a slope that differs from zero by 4.7$\sigma$. Comparisons to model calculations incorporating different formulations of jet quenching are reported. These comparisons indicate that the observed yield enhancement arises from the response of the QGP medium to jet propagation

Probing the Chiral Magnetic Wave with charge-dependent flow measurements in Pb-Pb collisions at the LHC

International audienceThe Chiral Magnetic Wave (CMW) phenomenon is essential to provide insights into the strong interaction in QCD, the properties of the quark-gluon plasma, and the topological characteristics of the early universe, offering a deeper understanding of fundamental physics in high-energy collisions. Measurements of the charge-dependent anisotropic flow coefficients are studied in Pb-Pb collisions at center-of-mass energy per nucleon-nucleon collision $\sqrt{s_{\mathrm{NN}}}=$ 5.02 TeV to probe the CMW. In particular, the slope of the normalized difference in elliptic ($v_{2}$) and triangular ($v_{3}$) flow coefficients of positively and negatively charged particles as a function of their event-wise normalized number difference, is reported for inclusive and identified particles. The slope $r_{3}^{\rm Norm}$ is found to be larger than zero and to have a magnitude similar to $r_{2}^{\rm Norm}$, thus pointing to a large background contribution for these measurements. Furthermore, $r_{2}^{\rm Norm}$ can be described by a blast wave model calculation that incorporates local charge conservation. In addition, using the event shape engineering technique yields a fraction of CMW ($f_{\rm CMW}$) contribution to this measurement which is compatible with zero. This measurement provides the very first upper limit for $f_{\rm CMW}$, and in the 10-60% centrality interval it is found to be 26% (38%) at 95% (99.7%) confidence level

Charged-particle production as a function of the relative transverse activity classifier in pp, p−-Pb, and Pb−-Pb collisions at the LHC

International audienceMeasurements of charged-particle production in pp, p$-$Pb, and Pb$-$Pb collisions in the toward, away, and transverse regions with the ALICE detector are discussed. These regions are defined event-by-event relative to the azimuthal direction of the charged trigger particle, which is the reconstructed particle with the largest transverse momentum ($p_{\mathrm{T}}^{\rm trig}$) in the range $8<p_{\mathrm{T}}^{\rm trig}<15$ GeV$/c$. The toward and away regions contain the primary and recoil jets, respectively; both regions are accompanied by the underlying event (UE). In contrast, the transverse region perpendicular to the direction of the trigger particle is dominated by the so-called UE dynamics, and includes also contributions from initial- and final-state radiation. The relative transverse activity classifier, $R_{\mathrm{T}}=N_{\mathrm{ch}}^{\mathrm{T}}/\langle N_{\mathrm{ch}}^{\mathrm{T}}\rangle$, is used to group events according to their UE activity, where $N_{\mathrm{ch}}^{\mathrm{T}}$ is the charged-particle multiplicity per event in the transverse region and $\langle N_{\mathrm{ch}}^{\mathrm{T}}\rangle$ is the mean value over the whole analysed sample. The energy dependence of the $R_{\mathrm{T}}$ distributions in pp collisions at $\sqrt{s}=2.76$, 5.02, 7, and 13 TeV is reported, exploring the Koba-Nielsen-Olesen (KNO) scaling properties of the multiplicity distributions. The first measurements of charged-particle $p_{\rm T}$ spectra as a function of $R_{\mathrm{T}}$ in the three azimuthal regions in pp, p$-$Pb, and Pb$-$Pb collisions at $\sqrt{s_{\rm NN}}=5.02$ TeV are also reported. Data are compared with predictions obtained from the event generators PYTHIA 8 and EPOS LHC. This set of measurements is expected to contribute to the understanding of the origin of collective-like effects in small collision systems (pp and p$-$Pb)