Between March and April 2020, Cyprus and Greece health authorities enforced three escalated levels of public health interventions to control the COVID-19 pandemic. We quantified compliance of 108 ...asthmatic schoolchildren (53 from Cyprus, 55 from Greece, mean age 9.7 years) from both countries to intervention levels, using wearable sensors to continuously track personal location and physical activity. Changes in 'fraction time spent at home' and 'total steps/day' were assessed with a mixed-effects model adjusting for confounders. We observed significant mean increases in 'fraction time spent at home' in Cyprus and Greece, during each intervention level by 41.4% and 14.3% (level 1), 48.7% and 23.1% (level 2) and 45.2% and 32.0% (level 3), respectively. Physical activity in Cyprus and Greece demonstrated significant mean decreases by - 2,531 and - 1,191 (level 1), - 3,638 and - 2,337 (level 2) and - 3,644 and - 1,961 (level 3) total steps/day, respectively. Significant independent effects of weekends and age were found on 'fraction time spent at home'. Similarly, weekends, age, humidity and gender had an independent effect on physical activity. We suggest that wearable technology provides objective, continuous, real-time location and activity data making possible to inform in a timely manner public health officials on compliance to various tiers of public health interventions during a pandemic.
Sepsis is a dysregulated host response to infection related to devastating outcomes. Recently, interest has been shifted towards apoptotic and antiapoptotic pathobiology. Apoptosis is executed ...through the activation of caspases regulated by a number of antiapoptotic proteins, such as survivin. The survivin and caspases' responses to sepsis have not yet been elucidated. This is a multicenter prospective observational study concerning patients with sepsis (n = 107) compared to patients with traumatic systemic inflammatory response syndrome (SIRS) (n = 75) and to healthy controls (n = 89). The expression of survivin was quantified through real-time quantitative polymerase chain reaction for the different survivin splice variants (wild type-WT, ΔEx3, 2B, 3B) in peripheral blood leukocytes. The apoptotic or antiapoptotic tendency was specified by measuring survivin-WT, caspase-3, and -9 serum protein concentrations through enzyme-linked immunosorbent assay. The survivin-WT, -2B, -ΔΕx3 mRNA, survivin protein, and caspases showed an escalated increase in SIRS and sepsis, whereas survivin-3B was repressed in sepsis (p < 0.05). Survivin correlated with IL-8 and caspase-9 (p < 0.01). For discriminating sepsis, caspase-9 achieved the best receiver operating characteristic curve (AUROC) of 0.95. In predicting mortality, caspase-9 and survivin protein achieved an AUROC of 0.70. In conclusion, specific apoptotic and antiapoptotic pathways might represent attractive targets for future research in sepsis.
Individuals with type 1 diabetes (T1D) are at increased risk of infections from vaccine-preventable diseases. This study focuses on compliance of T1D patients to the recommended vaccination schedule, ...vaccination of their close contacts for influenza and on factors potentially contributing to vaccination program deviations.
The study population comprised children, adolescents and adults with T1D under follow-up at the Department of Pediatrics University Hospital and the Diabetic Center General Hospital, Heraklion, Crete-Greece. Data were extracted, following informed consent, from individual's vaccination booklet, medical files and telephone interview. Vaccination records, demographic parameters, glycemic control and influenza vaccination of close contacts were assessed.
The study included 258 participants (111 children/adolescents, 147 adults). Vaccination coverage for influenza was 76.7% for children, 64.4% for adults, for PCV 90.9% for children, but only 10.8% for the 23-valent, for hepatitis B 99% for children and 78.2% for adults. Youngsters were vaccinated against Hib 91.9%, meningococcus C 98.2%, measles-mumps-rubella 90.3%, chickenpox 86.4%, hepatitis A 76.5% and HPV 42.5%. Less than 65% of all individuals were fully vaccinated for diphtheria-tetanus-pertussis and meningococcus ACWY. Approximately 50% of the 605 close contacts were not vaccinated against influenza. Individuals with better glycemic status seemed to adhere to the recommended schedule and had a better vaccinated family environment.
Vaccination coverage for T1D individuals was sufficient regarding the majority of routine childhood vaccines, but less for adolescence and group-specific vaccines. Their family contacts were not sufficiently vaccinated for influenza. Targeted interventions are required in order to increase vaccination rates.
Critical illness constitutes a serious derangement of metabolism. The aim of our study was to compare acute phase metabolic patterns in children with sepsis (S) or severe sepsis/septic shock (SS) to ...those with severe traumatic brain injury (TBI) and healthy controls (C) and to evaluate their relations to neutrophil, lymphocyte and monocyte expressions of CD64 and CD11b.
Sixty children were enrolled in the study. Forty-five children with systemic inflammatory response syndrome (SIRS) were classified into three groups: TBI (n = 15), S (n = 15), and SS (n = 15). C consisted of 15 non- SIRS patients undergoing screening tests for minor elective surgery. Blood samples were collected within 6 hours after admission for flow cytometry of neutrophil, lymphocyte and monocyte expression of CD64 and CD11b (n = 60). Procalcitonin (PCT), C-reactive protein (CRP), glucose, triglycerides (TG), total cholesterol (TC), high (HDL) or low-density-lipoproteins (LDL) were also determined in all groups, and repeated on day 2 and 3 in the 3 SIRS groups (n = 150).
CRP, PCT and TG (p < 0.01) were significantly increased in S and SS compared to TBI and C; glucose did not differ among critically ill groups. Significantly lower were the levels of TC, LDL, and HDL in septic groups compared to C and to moderate changes in TBI (p < 0.0001) but only LDL differed between S and SS (p < 0.02). Among septic patients, PCT levels declined significantly (p < 0.02) with time, followed by parallel decrease of HDL (p < 0.03) and increase of TG (p < 0.02) in the SS group. Neutrophil CD64 (nCD64) expression was higher in patients with SS (81.2%) and S (78.8%) as compared to those with TBI (5.5%) or C (0.9%, p < 0.0001). nCD64 was positively related with CRP, PCT, glucose, and TG (p < 0.01) and negatively with TC, LDL, and HDL (p < 0.0001), but not with severity of illness, hematologic indices, length of stay or mechanical ventilation duration.
In sepsis, the early stress-metabolic pattern is characterized by a high (nCD64, glucose, TG) - low (TC, HDL, LDL) combination in contrast to the moderate pattern of TBI in which only glucose increases combined with a moderate cholesterol - lipoprotein decrease. These early metabolic patterns persist the first 3 days of acute illness and are associated with the acute phase CD64 expression on neutrophils.
Increased morbidity/mortality due to vaccine preventable diseases (VPD) is encountered in type 2 diabetes (T2D) people. Aim of this study was to assess their vaccination coverage and describe trends ...possibly affecting compliance.
Information on vaccination coverage was retrieved from either documents or interview provided by patients, and/or their vaccination record card at a specialized outpatient diabetes center. The selection of the patients was arbitrary.
An increasing vaccination rate for influenza was observed from 2018 to 2020 among 372 participants. The vaccination coverage for
was 67.2% (PCV13), 20.4% (PPSV23), 26.3% for herpes zoster in individuals ≥60 years, 1.9% for tetanus-diphtheria-pertussis and 1.1% for hepatitis B. A 10.2% of participants were found to be unvaccinated. Vaccination uptake for influenza and PCV13 was related to age, ≥3 comorbidities and long-term follow-up. T2D individuals consecutively vaccinated for influenza were 3.78 times more likely to be also vaccinated with PCV13.
Vaccination rates of patients with T2D show an increasing trend, especially for influenza and
, although the one for
was low. Older people seem more prone to vaccination, the one for herpes zoster was low with infected patients remaining unvaccinated while significantly low coverage was observed for other VPDs. The findings are important to improve effectiveness of preventative services.
Abstract Background aims Age-related changes that could affect the biologic features of mesenchymal stromal cells (MSC), such as a decrease in proliferation and osteoblast differentiation capacity ...and an increase of senescence markers and apoptosis, have been reported recently. The aim of this study was the evaluation of age-related characteristics and the correlation of age with the functional properties of MSC. Methods The doubling time (DT), colony-forming unit–fibroblast (CFU-F) colonies and surface antigen expression of MSC isolated from bone marrow (BM) of children (C-MSC) were compared with those from adults (A-MSC). The expression of Oct-4 and Nanog transcripts and the relative telomere length were evaluated in both groups. Results DT values were lower in C-MSC compared with A-MSC, and a higher CFU-F count was observed in children. However, the expression of Oct-4 and Nanog did not differ between C-MSC and A-MSC and was not correlated with the proliferative capacity. The telomere length was significantly higher in C-MSC compared with A-MSC. Conclusions These data suggest that children's BM-derived MSC could be a more advantageous source of these cells for tissue engineering and cell therapy.
Oxidative stress is considered pivotal in the pathophysiology of sepsis. Oxidants modulate heat shock proteins (Hsp), interleukins (IL), and cell death pathways, including apoptosis. This multicenter ...prospective observational study was designed to ascertain whether an oxidant/antioxidant imbalance is an independent sepsis discriminator and mortality predictor in intensive care unit (ICU) patients with sepsis (
= 145), compared to non-infectious critically ill patients (
= 112) and healthy individuals (
= 89). Serum total oxidative status (TOS) and total antioxidant capacity (TAC) were measured by photometric testing. IL-6, -8, -10, -27, Hsp72/90 (ELISA), and selected antioxidant biomolecules (Ζn, glutathione) were correlated with apoptotic mediators (caspase-3, capsase-9) and the central anti-apoptotic survivin protein (ELISA, real-time PCR). A wide scattering of TOS, TAC, and TOS/TAC in all three groups was demonstrated. Septic patients had an elevated TOS/TAC, compared to non-infectious critically ill patients and healthy individuals (
= 0.001). TOS/TAC was associated with severity scores, procalcitonin, IL-6, -10, -27, IFN-γ, Hsp72, Hsp90, survivin protein, and survivin isoforms -2B, -ΔΕx3, -WT (
< 0.001). In a propensity probability (age-sex-adjusted) logistic regression model, only sepsis was independently associated with TOS/TAC (Exp(B) 25.4,
< 0.001). The AUC
(0.96 (95% CI = 0.93-0.99)) was higher than AUC
(z = 20,
< 0.001) or AUC
(z = 3.1,
= 0.002) in distinguishing sepsis. TOS/TAC, TOS, survivin isoforms -WT and -2B, Hsp90, IL-6, survivin protein, and repressed TAC were strong predictors of mortality (
< 0.01). Oxidant/antioxidant status is impaired in septic compared to critically ill patients with trauma or surgery and is related to anti-apoptotic, inflammatory, and innate immunity alterations. The unpredicted TOS/TAC imbalance might be related to undefined phenotypes in patients and healthy individuals.
Increased levels of asparagine synthetase (ASNS), an enzyme producing intracellular asparagine, have been implicated in the development of asparaginase resistance. The aim of this study was to assess ...ASNS mRNA and protein expression in bone marrow cell populations of children with acute lymphoblastic leukemia (ALL). Bone marrow mononuclear cells at diagnosis, day 33 of treatment, and after completion of chemotherapy were isolated and studied. ASNS mRNA expression was assessed by real-time PCR, and protein levels by Western blot. Our results indicate that MSC ASNS mRNA expression is upregulated in ALL samples compared to controls. ASNS expression of mesenchymal stromal cells (MSC) was found to be 2.3 times higher than that of blasts at diagnosis of ALL. We also observed that the values of the ASNS mRNA of MSC seem to reach a peak at diagnosis, and tend to decline with treatment. No correlation was found between the ASNS mRNA and protein levels. Chemotherapy does not exert any effect on the protein expression. Variability of asparaginase-induced effect may be attributable to factors involved in the interaction of hematopoietic cells with their microenvironment.
Mesenchymal stromal cells (MSCs) have a supportive role in hematopoiesis and as components of the bone marrow (BM) microenvironment may present alterations during acute lymphoblastic leukemia (ALL) ...and be affected by chemotherapeutic agents. We examined the biological and functional characteristics of MSCs in ALL diagnosis and treatment and their effect on MSC qualitative properties.
Immunophenotypic characterization, evaluation of clonogenicity, and proliferative capacity were measured. Apoptotic features, cell-cycle analysis, and stromal cell-derived factor 1α and angiopoietin-1 levels in MSC supernatant at diagnosis and in different phases of treatment were assessed. Chemotherapy was administered according to the Berlin-Frankfurt-Munster-2000 protocol. BM samples from children with solid tumors without BM involvement were used as the control group.
The morphology, the immunophenotypic profile, and the apoptotic characteristics of the MSCs were not affected by leukemia. The secretion of factors involved in the trafficking of hematopoietic cells in the BM seems to be upregulated at diagnosis in comparison to the treatment phases. MSCs are influenced by the disease in terms of their functional characteristics such as clonogenicity and proliferation rate. These effects cease as soon as treatment is initiated. Chemotherapy does not seem to exert any effect on any of the MSC features examined.
MSCs from children with ALL are affected by their interaction with the leukemic environment, but this phenomenon ceases upon treatment initiation, while no effect is observed by chemotherapy itself.
To examine whether the septic profiles of heat shock protein 72, heat shock protein 90α, resistin, adiponectin, oxygen consumption, CO2 production, energy expenditure, and metabolic pattern, along ...with illness severity, nutritional, and inflammatory indices, differ between adult and pediatric patients compared with systemic inflammatory response syndrome and healthy controls. To evaluate whether these biomolecules may discriminate sepsis from systemic inflammatory response syndrome in adult and pediatric patients.
Prospective cohort study.
University ICU and PICU.
Seventy-eight adults (sepsis/23; systemic inflammatory response syndrome/23; healthy controls/33), 67 children (sepsis/18; systemic inflammatory response syndrome/23; controls/27), mechanically ventilated.
None.
Flow cytometry determined mean fluorescence intensity for monocyte or neutrophil heat shock protein expression. Resistin, adiponectin, and extracellular heat shock proteins were measured using enzyme-linked immunosorbent assay; energy expenditure by E-COVX (GE Healthcare). Genomic DNA was extracted with PureLink Genomic DNA kit (Invitrogen, Carlsbad, CA) to detect heat shock protein 72 single nucleotide polymorphisms. Similarly, in adult and pediatric patients, Acute Physiology and Chronic Evaluation-II/Acute Physiology and Pediatric Risk of Mortality-III, Simplified Acute Physiology Score-III, C-reactive protein, lactate, and resistin were higher and myocardial contractility, monocyte heat shock protein 72, oxygen consumption, CO2 production, energy expenditure, metabolic pattern, glucose, and albumin lower in sepsis compared with systemic inflammatory response syndrome or controls (p < 0.05). For discriminating sepsis from systemic inflammatory response syndrome, resistin, extracellular heat shock protein 90α, and lactate achieved a receiver operating characteristic curve greater than 0.80 in children and greater than 0.75 in adults (p < 0.05). In both, adults and children, genotype heat shock protein 72 analysis did not disclose any diagnosis or mortality group differences regarding either rs6457452 or rs1061581 haplotypes.
Sepsis presents with similar profiles in adult and pediatric patients, characterized by enhanced inflammatory hormonal response and by repressed innate immunity, metabolism, and myocardial contractility. These features early distinguish sepsis from systemic inflammatory response syndrome across all age groups.
PDF
