1,995 research outputs found
Climate Change and Childhood Respiratory Health: A Call to Action for Paediatricians
Climate change (CC) is one of the main contributors to health emergencies worldwide. CC appears to be closely interrelated with air pollution, as some pollutants like carbon dioxide (CO2), nitrogen oxides (NOx) and black carbon are naturally occurring greenhouse gases. Air pollution may enhance the allergenicity of some plants and, also, has an adverse effect on respiratory health. Children are a uniquely vulnerable group that suffers disproportionately from CC burden. The increasing global warming related to CC has a big impact on plants' lifecycles, with earlier and longer pollen seasons, as well as higher pollen production, putting children affected by asthma and allergic rhinitis at risk for exacerbations. Extreme weather events may play a role too, not only in the exacerbations of allergic respiratory diseases but, also, in favouring respiratory infections. Even though paediatricians are already seeing the impacts of CC on their patients, their knowledge about CC-related health outcomes with specific regards to children's respiratory health is incomplete. This advocates for paediatricians' increased awareness and a better understanding of the CC impact on children's respiratory health. Having a special responsibility for children, paediatricians should actively be involved in policies aimed to protect the next generation from CC-related adverse health effects. Hence, there is an urgent need for them to take action and successfully educate families about CC issues. This paper aims at reviewing the evidence of CC-related environmental factors such as temperature, humidity, rainfall and extreme events on respiratory allergic diseases and respiratory infections in children and proposing specific actionable items for paediatricians to deal with CC-related health issues in their clinical practice
Genetic profiling of autoinflammatory disorders in patients with periodic fever: a prospective study
Periodic fever syndromes (PFS) are an emerging group of autoinflammatory disorders. Clinical overlap exists and multiple genetic analyses may be needed to assist diagnosis. We evaluated the diagnostic value of a 5-gene sequencing panel (5GP) in patients with undiagnosed PFS
The Substructure Hierarchy in Dark Matter Haloes
We present a new algorithm for identifying the substructure within simulated
dark matter haloes. The method is an extension of that proposed by Tormen et
al. (2004) and Giocoli et al. (2008a), which identifies a subhalo as a group of
self-bound particles that prior to being accreted by the main progenitor of the
host halo belonged to one and the same progenitor halo (hereafter satellite).
However, this definition does not account for the fact that these satellite
haloes themselves may also have substructure, which thus gives rise to
sub-subhaloes, etc. Our new algorithm identifies substructures at all levels of
this hierarchy, and we use it to determine the mass function of all
substructure (counting sub-haloes, sub-subhaloes, etc.). On average, haloes
which formed more recently tend to have a larger mass fraction in substructure
and to be less concentrated than average haloes of the same mass. We provide
quantitative fits to these correlations. Even though our algorithm is very
different from that of Gao et al. (2004), we too find that the subhalo mass
function per unit mass at redshift z = 0 is universal. This universality
extends to any redshift only if one accounts for the fact that host haloes of a
given mass are less concentrated at higher redshifts, and concentration and
substructure abundance are anti-correlated. This universality allows a simple
parametrization of the subhalo mass function integrated over all host halo
masses, at any given time. We provide analytic fits to this function which
should be useful in halo model analyses which equate galaxies with halo
substructure when interpreting clustering in large sky surveys. Finally, we
discuss systematic differences in the subhalo mass function that arise from
different definitions of (host) halo mass.Comment: 18 pages, 24 figures, accepted for publication on MNRA
Genetic profiling of auto-inflammatory disorders in patients with periodic fever: a prospective study
Prognostic and Predictive Role of Body Composition in Metastatic Neuroendocrine Tumor Patients Treated with Everolimus: A Real-World Data Analysis
Neuroendocrine tumors (NETs) are rare neoplasms frequently characterized by an up- regulation of the mammalian rapamycin targeting (mTOR) pathway resulting in uncontrolled cell proliferation. The mTOR pathway is also involved in skeletal muscle protein synthesis and in adipose tissue metabolism. Everolimus inhibits the mTOR pathway, resulting in blockade of cell growth and tumor progression. The aim of this study is to investigate the role of body composition in- dexes in patients with metastatic NETs treated with everolimus. The study population included 30 patients with well-differentiated (G1-G2), metastatic NETs treated with everolimus at the IRCCS Romagnolo Institute for the Study of Tumors (IRST) âDino Amadoriâ, Meldola (FC), Italy. The body composition indexes (skeletal muscle index [SMI] and adipose tissue indexes) were assessed by measuring on a computed tomography (CT) scan the cross-sectional area at L3 at baseline and at the first radiological assessment after the start of treatment. The body mass index (BMI) was assessed at baseline. The median progression-free survival (PFS) was 8.9 months (95% confidence interval [CI]: 3.4â13.7 months). The PFS stratified by tertiles was 3.2 months (95% CI: 0.9â10.1 months) in patients with low SMI (tertile 1), 14.2 months (95% CI: 2.3 months-not estimable [NE]) in patients with intermediate SMI (tertile 2), and 9.1 months (95% CI: 2.7 months-NE) in patients with high SMI (tertile 3) (p = 0.039). Similarly, the other body composition indexes also showed a statistically significant difference in the three groups on the basis of tertiles. The median PFS was 3.2 months (95% CI: 0.9â6.7 months) in underweight patients (BMI 18.49 kg/m2) and 10.1 months (95% CI: 3.7â28.4 months) in normal-weight patients (p = 0.011). There were no significant differences in terms of overall survival. The study showed a correlation between PFS and the body composition indexes in patients with NETs treated with everolimus, underlining the role of adipose and muscle tissue in these patients
Impact of safety-related dose reductions or discontinuations on sustained virologic response in HCV-infected patients: Results from the GUARD-C Cohort
BACKGROUND:
Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD) and their impact on sustained virologic response (SVR) in patients receiving peginterferon alfa/ribavirin in routine practice.
METHODS:
A total of 3181 HCV-mono-infected treatment-naive patients were assigned to 24 or 48 weeks of peginterferon alfa/ribavirin by their physician. Patients were categorized by time-to-first sr-RD (Week 4/12). Detailed analyses of the impact of sr-RD on SVR24 (HCV RNA <50 IU/mL) were conducted in 951 Caucasian, noncirrhotic genotype (G)1 patients assigned to peginterferon alfa-2a/ribavirin for 48 weeks. The probability of SVR24 was identified by a baseline scoring system (range: 0-9 points) on which scores of 5 to 9 and <5 represent high and low probability of SVR24, respectively.
RESULTS:
SVR24 rates were 46.1% (754/1634), 77.1% (279/362), 68.0% (514/756), and 51.3% (203/396), respectively, in G1, 2, 3, and 4 patients. Overall, 16.9% and 21.8% patients experienced 651 sr-RD for peginterferon alfa and ribavirin, respectively. Among Caucasian noncirrhotic G1 patients: female sex, lower body mass index, pre-existing cardiovascular/pulmonary disease, and low hematological indices were prognostic factors of sr-RD; SVR24 was lower in patients with 651 vs. no sr-RD by Week 4 (37.9% vs. 54.4%; P = 0.0046) and Week 12 (41.7% vs. 55.3%; P = 0.0016); sr-RD by Week 4/12 significantly reduced SVR24 in patients with scores <5 but not 655.
CONCLUSIONS:
In conclusion, sr-RD to peginterferon alfa-2a/ribavirin significantly impacts on SVR24 rates in treatment-naive G1 noncirrhotic Caucasian patients. Baseline characteristics can help select patients with a high probability of SVR24 and a low probability of sr-RD with peginterferon alfa-2a/ribavirin
Association of mesenchymal stem cells with platelet rich plasma on the repair of critical calvarial defects in mice
Genetic determinants in a critical domain of ns5a correlate with hepatocellular carcinoma in cirrhotic patients infected with hcv genotype 1b
HCV is an important cause of hepatocellular carcinoma (HCC). HCV NS5A domainâ1 interacts with cellular proteins inducing proâoncogenic pathways. Thus, we explore genetic variations in NS5A domainâ1 and their association with HCC, by analyzing 188 NS5A sequences from HCV genotypeâ1b infected DAAânaĂŻve cirrhotic patients: 34 with HCC and 154 without HCC. Specific NS5A mutations significantly correlate with HCC: S3T (8.8% vs. 1.3%, p = 0.01), T122M (8.8% vs. 0.0%, p < 0.001), M133I (20.6% vs. 3.9%, p < 0.001), and Q181E (11.8% vs. 0.6%, p < 0.001). By multivariable analysis, the presence of >1 of them independently correlates with HCC (OR (95%CI): 21.8 (5.7â82.3); p < 0.001). Focusing on HCCâgroup, the presence of these mutations correlates with higher viremia (median (IQR): 5.7 (5.4â6.2) log IU/mL vs. 5.3 (4.4â5.6) log IU/mL, p = 0.02) and lower ALT (35 (30â71) vs. 83 (48â108) U/L, p = 0.004), suggesting a role in enhancing viral fitness without affecting necroinflammation. Notably, these mutations reside in NS5A regions known to interact with cellular proteins crucial for cellâcycle regulation (p53, p85âPIK3, and ÎČâ catenin), and introduce additional phosphorylation sites, a phenomenon known to ameliorate NS5A interaction with cellular proteins. Overall, these results provide a focus for further investigations on molecular bases of HCVâmediated oncogenesis. The role of these NS5A domainâ1 mutations in triggering proâoncogenic stimuli that can persist also despite achievement of sustained virological response deserves further investigation
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