Catechins as a Potential Dietary Supplementation in Prevention of Comorbidities Linked with Down Syndrome

Plant-derived polyphenols flavonoids are increasingly being recognized for their medicinal potential. These bioactive compounds derived from plants are gaining more interest in ameliorating adverse health risks because of their low toxicity and few side effects. Among them, therapeutic approaches demonstrated the efficacy of catechins, a major group of flavonoids, in reverting several aspects of Down syndrome, the most common genomic disorder that causes intellectual disability. Down syndrome is characterized by increased incidence of developing Alzheimer’s disease, obesity, and subsequent metabolic disorders. In this focused review, we examine the main effects of catechins on comorbidities linked with Down syndrome. We also provide evidence of catechin effects on DYRK1A, a dosage-sensitive gene encoding a protein kinase involved in brain defects and metabolic disease associated with Down syndrome.     

Impact of G-CSF Prophylaxis on Chemotherapy Dose-Intensity,Link Between Dose-Intensity and Survival in Patients with Metastatic Pancreatic Adenocarcinoma

BackgroundIn metastatic pancreatic adenocarcinoma, few data are available on the use of granulocyte-colony stimulating factor (G-CSF) prophylaxis and its impact on dose-intensity (DI), or the link between DI and progression-free survival (PFS). This study assessed the impact of G-CSF prophylaxis on the DI received by patients and the relationship between full DI and PFS according to chemotherapy regimens.Patients and MethodsPatients from three first-line randomized phase II clinical trials were included in this retrospective cohort. G-CSF prophylaxis groups were identified and balanced according to baseline characteristics using a propensity score. Patients were classified into 2 treatment groups (FOLFIRINOX vs FOLFIRI/nab-paclitaxel (NAB)). DI was a binary variable (full/reduced). Adverse events were defined using NCI-CTCAE v4.0.ResultsOf the 498 patients, 154 (31%) were in “prophylaxis” group; 179 (36%) were treated by FOLFIRINOX and 319 (64%) by FOLFIRI/NAB. In FOLFIRINOX group, G-CSF prophylaxis was significantly associated with a higher rate of full DI (OR, 5.07; 95% CI, 1.52-16.90; P < .01) while in FOLFIRI/NAB group, it was significantly associated with a lower rate of full DI (OR, 0.23; 95% CI, 0.06-0.83; P = .03). Full DI was associated with a non-significant increase in PFS (FOLFIRINOX group: HR 0.83; 95% CI, 0.59-1.16; P = .27; FOLFIRI/NAB group: HR 0.84; 95% CI, 0.63-1.11; P = .22).ConclusionGranulocyte-colony stimulating factor prophylaxis was associated with a higher rate of full DI with FOLFIRINOX. Full DI was associated with a non-significant increase in PFS. These results need to be confirmed prospectively.     

Lung Transplant Recipients Immunogenicity after Heterologous ChAdOx1 nCoV-19—BNT162b2 mRNA Vaccination

(1) Background: High immunosuppressive regimen in lung transplant recipients (LTRs) hampers the immune response to vaccination. We prospectively investigated the immunogenicity of heterologous ChAdOx1 nCoV-19-BNT162b2 mRNA vaccination in an LTR cohort. (2) Methods: Forty-nine COVID-19 naïve LTRs received a two-dose regimen ChAdOx1 nCoV-19 vaccine. A subset of 32 patients received a booster dose of BNT162b2 mRNA vaccine 18 weeks after the second dose. (3) Results: Two-doses of ChAdOx1 nCoV-19 induced poor immunogenicity with 7.2% seropositivity at day 180 and low neutralizing capacities. The BNT162b2 mRNA vaccine induced significant increases in IgG titers with means of 197.8 binding antibody units per milliliter (BAU/mL) (95% CI 0–491.4) and neutralizing antibodies, with means of 76.6 AU/mL (95% CI 0–159.6). At day 238, 32.2% of LTRs seroconverted after the booster dose. Seroneutralization capacities against Delta and Omicron variants were found in only 13 and 9 LTRs, respectively. Mycophenolate mofetil and high-dose corticosteroids were associated with a weak serological response. (4) Conclusions: The immunogenicity of a two-dose ChAdOx1 nCoV-19 vaccine regimen was very poor in LTRs, but was significantly enhanced after the booster dose in one-third of LTRs. In immunocompromised individuals, the administration of a fourth dose may be considered to increase the immune response against SARS-CoV-2.     

Hypertension and Associated Risk Factors among Children with Intellectual Disability: A Cross-Sectional Study

To investigate the prevalence of hypertension and associated risk factors in Chinese children with intellectual disability, a cross-sectional study was conducted in a sample of 558 children with intellectual disability aged 6–18 years in Hong Kong, and 452 (81.0%) with valid data were included in the data analysis. Blood pressure was measured according to a standard protocol. Hypertension was defined using the age-, gender-, and height-specific classification criteria recommended by the 2018 Chinese Guidelines for Children. Multivariate and hierarchical logistic regression was fitted to examine the associations of hypertension with potential risk factors. Overall, 31.4% of the participants were classified as having hypertension. Obese children were more likely to develop hypertension than non-obese children (adjusted OR = 2.77, 95% CI: 1.28, 5.99, p = 0.010). A paternal education of college or above and a paternal occupation of clerks, sales representatives, and workers were also associated with an increased risk of hypertension. The prevalence of hypertension is high among Chinese children with intellectual disability. Obesity was the strongest risk factor. Further longitudinal studies are warranted to confirm our findings. Nevertheless, preventions against obesity are promising to receive doubled benefits in reducing both obesity and hypertension, given its strong relationship with hypertension in this special population.     

Immune-mediated neurological syndromes in SARS-CoV-2-infected patients

Journal of Neurology - Evidence of immune-mediated neurological syndromes associated with the severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection is limited. We therefore...     

Manufacturing of a Magnetic Composite Flexible Filament and Optimization of a 3D Printed Wideband Electromagnetic Multilayer Absorber in X-Ku Frequency Bands

With the multiplication of electronic devices in our daily life, there is a need for tailored wideband electromagnetic (EM) absorbers that could be conformed on any type of surface-like antennas for interference attenuation or military vehicles for stealth applications. In this study, a wideband flexible flat electromagnetic absorber compatible with additive manufacturing has been studied in the X-Ku frequency bands. A multilayer structure has been optimized using a genetic algorithm (GA), adapting the restrictions of additive manufacturing and exploiting the EM properties of loaded and non-loaded filaments, of which the elaboration is described. After optimization, a bi-material multilayer absorber with a thickness of 4.1 mm has been designed to provide a reflectivity below −12 dB between 8 and 18 GHz. Finally, the designed multilayer structure was 3D-printed and measured in an anechoic chamber, achieving −11.8 dB between 7 and 18 GHz. Thus, the development of dedicated materials has demonstrated the strong potential of additive technologies for the manufacturing of thin wideband flexible EM absorbers.     

Flow cytometry thresholds of myeloperoxidase detection to discriminate between acute lymphoblastic or myeloblastic leukaemia

The World Health Organization 2008 Classification emphasizes myeloperoxidase (MPO) detection as sufficient for assigning a blast population to the myeloid lineage. Published MPO positivity thresholds are 10% for flow cytometry (FCM) but 3% for cytochemistry. Here we re‐evaluated the FCM‐MPO threshold by comparing retrospectively 128 acute lymphoblastic leukaemias and 75 acute myeloid leukaemias without maturation, all assessed by benzidine‐based cytochemistry. A 13% threshold was found to be relevant using an isotype control as background‐reference (sensitivity 95·1%, specificity 91·7%). Residual normal lymphocytes proved to be an advantageous alternative reference, a threshold of 28% yielding improved 97·4% sensitivity and 96·1% specificity.     

Protection Against Type 1 Diabetes Upon Coxsackievirus B4 Infection and iNKT-Cell Stimulation: Role of Suppressive Macrophages

Invariant natural killer T (iNKT) cells belong to the innate immune system and exercise a dual role as potent regulators of autoimmunity and participate in responses against different pathogens. They have been shown to prevent type 1 diabetes development and to promote antiviral responses. Many studies in the implication of environmental factors on the etiology of type 1 diabetes have suggested a link between enteroviral infections and the development of this disease. This study of the pancreatropic enterovirus Coxsackievirus B4 (CVB4) shows that although infection accelerated type 1 diabetes development in a subset of proinsulin 2–deficient NOD mice, the activation of iNKT cells by a specific agonist, α-galactosylceramide, at the time of infection inhibited the disease. Diabetes development was associated with the infiltration of pancreatic islets by inflammatory macrophages, producing high levels of interleukin (IL)-1β, IL-6, and tumor necrosis factor-α and activation of anti-islet T cells. On the contrary, macrophages infiltrating the islets after CVB4 infection and iNKT-cell stimulation expressed a number of suppressive enzymes, among which indoleamine 2,3-dioxygenase was sufficient to inhibit anti-islet T-cell response and to prevent diabetes. This study highlights the critical interaction between virus and the immune system in the acceleration or prevention of type 1 diabetes.Type 1 diabetes is characterized by the destruction of pancreatic islet β-cells by autoreactive CD4 and CD8 T cells, leading to low insulin production and incapacity to regulate blood glucose levels (1). Despite numerous studies, the etiology of type 1 diabetes remains elusive. Besides genetics (2–4), environmental factors such as viral infections have been suggested as triggers of type 1 diabetes (5–7). Most striking of these infections are the type B Coxsackieviruses belonging to the enterovirus genus whose genome and anti-Coxsackievirus antibodies were detected more frequently in the blood of recently diagnosed patients compared with healthy controls (8,9). Besides, enteroviral RNA or enteroviral particles were directly detected in the pancreas of type 1 diabetic patients, whereas they were undetectable in the pancreas of healthy donors (9,10). In a mouse model of type 1 diabetes, Serreze et al. (11) showed that diabetes can develop rapidly after Coxsackievirus B4 (CVB4) infection if mice had an advanced age and sufficient insulitis. Others have reported that inefficient islet β-cell response, viral dose, and replication rate as well as a lack of islet neogenesis could also promote accelerated diabetes development after CVB4 infection (12–14).Natural killer T (NKT) cells are CD1d-restricted, nonconventional T cells recognizing self and exogenous glycolipids. Most NKT cells express an invariant T-cell receptor α chain, Vα14-Jα18 (Vα14) in mice and Vα24-Jα18 in humans, and are named invariant NKT (iNKT) cells. They can promptly secrete copious amounts of interferon-γ (IFN-γ) and interleukin (IL)-4 and provide maturation signals to dendritic cells (DCs) and lymphocytes, thereby contributing to both innate and acquired immunity (15,16). iNKT cells are potent regulatory cells that can inhibit autoimmunity and promote immune responses against pathogens (1,17). Diabetes can be prevented in NOD mice by increasing iNKT cell numbers and by iNKT-cell stimulation with exogenous ligands such as α-galactosylceramide (αGalCer) (15,18,19). NOD mice protected from diabetes by iNKT cells have weak T helper 1 anti-islet β-cell responses (20). Indeed, iNKT cells can impair the differentiation of anti-islet CD4 and CD8 T cells, which become hyporesponsive or anergic (21). Contrary to their suppressive role in type 1 diabetes, iNKT cells can enhance immune responses to pathogens such as parasites, bacteria, and viruses (22,23).Our previous studies conducted in a murine model of type 1 diabetes with lymphocytic choriomeningitis virus infection revealed that iNKT cells could promote systemic antiviral CD8 T-cell responses while inhibiting deleterious anti-islet T-cell responses, thereby preventing type 1 diabetes (24,25). In the present study, we investigated the role of iNKT cells after CVB4 infection, revealing that diabetes development following CVB4 infection is associated with the infiltration of inflammatory macrophages into the pancreatic islets with subsequent activation of anti-islet T cells. However, the activation of iNKT cells during CVB4 infection results in the infiltration of suppressive macrophages into pancreatic islets. Indoleamine 2,3-dioxygenase (IDO) expressed by these macrophages was critical for the inhibition of diabetes development.