Chronic lymphocytic leukemia (CLL) can be immunosuppressive in humans and mice, and CLL cells share multiple phenotypic markers with regulatory B cells that are competent to produce interleukin ...(IL)-10 (B10 cells). To identify functional links between CLL cells and regulatory B10 cells, the phenotypes and abilities of leukemia cells from 93 patients with overt CLL to express IL-10 were assessed. CD5(+) CLL cells purified from 90% of the patients were IL-10-competent and secreted IL-10 following appropriate ex vivo stimulation. Serum IL-10 levels were also significantly elevated in CLL patients. IL-10-competent cell frequencies were higher among CLLs with IgV(H) mutations, and correlated positively with TCL1 expression. In the TCL1-transgenic (TCL1-Tg) mouse model of CLL, IL-10-competent B cells with the cell surface phenotype of B10 cells expanded significantly with age, preceding the development of overt, CLL-like leukemia. Malignant CLL cells in TCL1-Tg mice also shared immunoregulatory functions with mouse and human B10 cells. Serum IL-10 levels varied in TCL1-Tg mice, but in vivo low-dose lipopolysaccharide treatment induced IL-10 expression in CLL cells and high levels of serum IL-10. Thus, malignant IL-10-competent CLL cells exhibit regulatory functions comparable to normal B10 cells that may contribute to the immunosuppression observed in patients and TCL1-Tg mice.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Background
Celiac disease (CD) is a chronic gluten‐sensitive enteropathy. Life‐long gluten‐free diet (GFD) is the only therapeutic option; however, it may contribute to the consumption of an ...unbalanced diet. The present study aimed to evaluate the dietary intake of CD affected children on a GFD and compare it with non‐celiac children and with Italian nutritional intakes recommendations, as well as evaluate the contribution of commercially available gluten‐free products (GFPs).
Methods
Eighteen celiac children, median age 7.6 years, median GFD duration 4.2 years, and 18 non‐celiac controls, were enrolled in a cross‐sectional age‐matched study. Dietary intakes of both groups were collected using a food frequency questionnaire and a 24‐hour dietary recall. Nutritional intakes were compared between the group and controls and with Italian dietary reference values. The contribution of GFPs to energy and macronutrient intakes was evaluated.
Results
Median energy intake was significantly higher in CD patients than in controls (8961.8 and 5761.0 kJ day−1; P < 0.001). CD subjects showed higher carbohydrate intakes and lower fat intakes compared to controls. Protein‐derived energy did not differ. By contrast to control subjects, energy derived from carbohydrate intakes in CD children met the Italian recommendations. Both children groups showed higher protein and fat intakes than recommended in Italy. GFPs consumption accounted for 36.3% of daily total energy intake.
Conclusions
Intakes of simple sugars, fats and protein exceeded the National recommendations for health. Children with CD had significantly higher energy intakes than controls, although body mass index was comparable across the groups. Lack of nutritional information for GFPs prevented complete dietary analysis of subfractions of fat and micronutrient intakes. This aspect need to be addressed if studies in this field are to be meaningful in the future.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Purpose
COVID-19 disease may result in a severe multisystem inflammatory syndrome in children (MIS-C), which in turn may alter thyroid function (TF). We assessed TF in MIS-C, evaluating its impact on ...disease severity.
Methods
We retrospectively considered children admitted with MIS-C to a single pediatric hospital in Milan (November 2019–January 2021). Non-thyroidal illness syndrome (NTIS) was defined as any abnormality in TF tests (FT3, FT4, TSH) in the presence of critical illness and absence of a pre-existing hormonal abnormality. We devised a disease severity score by combining severity scores for each organ involved. Glucose and lipid profiles were also considered. A principal component analysis (PCA) was performed, to characterize the mutual association patterns between TF and disease severity.
Results
Of 26 (19 M/7F) patients, median age 10.7 (IQR 5.8–13.3) years, 23 (88.4%) presented with NTIS. A low FT3 level was noted in 15/23 (65.3%), while the other subjects had varying combinations of hormone abnormalities (8/23, 34.7%). Mutually correlated variables related to organ damage and inflammation were represented in the first dimension (PC1) of the PCA. FT3, FT4 and total cholesterol were positively correlated and characterized the second axis (PC2). The third axis (PC3) was characterized by the association of triglycerides, TyG index and HDL cholesterol. TF appeared to be related to lipemic and peripheral insulin resistance profiles. A possible association between catabolic components and severity score was also noted.
Conclusions
A low FT3 level is common among MIS-C. TF may be useful to define the impact of MIS-C on children’s health and help delineate long term follow-up management and prognosis.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Complement plays an important role in the immunotherapeutic action of the anti-CD20 mAb rituximab, and therefore we investigated whether complement might be the limiting factor in rituximab therapy. ...Our in vitro studies indicate that at high cell densities, binding of rituximab to human CD20(+) cells leads to loss of complement activity and consumption of component C2. Infusion of rituximab in chronic lymphocytic leukemia patients also depletes complement; sera of treated patients have reduced capacity to C3b opsonize and kill CD20(+) cells unless supplemented with normal serum or component C2. Initiation of rituximab infusion in chronic lymphocytic leukemia patients leads to rapid clearance of CD20(+) cells. However, substantial numbers of B cells, with significantly reduced levels of CD20, return to the bloodstream immediately after rituximab infusion. In addition, a mAb specific for the Fc region of rituximab does not bind to these recirculating cells, suggesting that the rituximab-opsonized cells were temporarily sequestered by the mononuclear phagocytic system, and then released back into the circulation after the rituximab-CD20 complexes were removed by phagocytic cells. Western blots provide additional evidence for this escape mechanism that appears to occur as a consequence of CD20 loss. Treatment paradigms to prevent this escape, such as use of engineered or alternative anti-CD20 mAbs, may allow for more effective immunotherapy of chronic lymphocytic leukemia.
Abstract Background and aim Studies of adults and children with celiac disease (CD) performed mostly in tertiary care centers have reported an increased risk of overweight during gluten-free diet ...(GFD). We measured body mass index (BMI) of CD children followed by family pediatricians in order to estimate prevalence of underweight and overweight at diagnosis and to describe BMI changes during GFD. Methods and Results We compared 150 CD children (age range 2–16 yrs) under GFD from a median (IQR) time of 4.4 (4.2) years with 288 healthy children matched for gender and age. We also evaluated retrospectively BMI changes between CD diagnosis and the current evaluation. The median (IQR) BMI of CD patients was significantly lower than that of controls −0.38 (1.46) vs. 0.09 (1.18) SDS, p < 0.0001, Italian reference data. Using the International Obesity Task Force classifications, CD children were less frequently overweight or obese (12% vs. 23.3%, p = 0.014) and more frequently underweight (16% vs. 4.5%, p < 0.001) than controls. During GFD, there was a marked decrease of number of underweight subjects (13 vs. 27) and a minimal increase of number of overweight subjects (9 vs. 6) ( p < 0.001). Conclusions The frequency of overweight and obesity at diagnosis of CD and during GFD in children followed by family pediatricians is substantially lower than that reported in tertiary care centers. On the other hand, the high frequency of underweight at diagnosis confirms the need of careful personalized nutritional management.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Posttraumatic stress disorder (PTSD) has been linked to a wide array of risky and health-compromising behaviors, including risky sexual behavior (RSB). Cross-sectional studies reveal positive ...associations between emotion dysregulation and both PTSD and RSB. This study extended that work by exploring whether intermediate levels of emotion dysregulation across multiple dimensions account for the relation between baseline PTSD symptoms and RSB (i.e., number of vaginal sex partners, number of instances of condomless sex, and number of instances of risky/impulsive sex) 16 months later. Participants were 447 trauma-exposed young adult women from the community (60.0% White;
M
age = 21.80 years) who completed five assessments (separated by 4-month increments) over a 16-month period. Baseline PTSD symptoms were significantly positively associated with all emotion dysregulation dimensions at 8 months and the number of instances of risky/impulsive sex at 16 months. Further, results revealed significant indirect effects of baseline PTSD symptoms on (1) 16-month vaginal sex partners through both the nonacceptance of negative emotions and difficulties controlling impulsive behaviors when distressed at 8-month and (2) 16-month risky/impulsive sex through difficulties engaging in goal-directed behaviors when distressed at 8 months. Results provide support for the mediating roles of nonacceptance of negative emotions and difficulties controlling behaviors when distressed in the relation between PTSD symptoms and later RSB.
A subset of research exploring the long-term impact of child sexual abuse (CSA) has examined the adult interpersonal functioning of female survivors. The present review discusses empirical findings ...and critical methodological issues related to this important but often overlooked aspect of adult adjustment. Though characterized by several methodological limitations, this literature, as a whole, suggests that early sexual abuse represents a risk factor for a range of interpersonal dysfunction among female survivors, including problems with intimate partner relations, disturbed sexual functioning, and difficulties in the parental role. Suggested methodological improvements for future research include new approaches to the measurement of CSA and interpersonal variables, the need for comprehensive assessment of significant third variables, and the use of more representative sampling strategies.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Abstract This study used meta-analysis to examine the relationship between childhood exposure to domestic violence and children's internalizing, externalizing, and trauma symptoms. Results from 60 ...reviewed studies revealed mean weighted effect size d -values of .48 and .47 for the relationship between exposure to domestic violence and childhood internalizing and externalizing symptoms, respectively, indicating moderate effects. A larger mean weighted effect size d -value of 1.54 was obtained for the relationship between exposure to domestic violence and childhood trauma symptoms, though this figure was based on only six studies. Moderator analyses for gender showed that the relationship between exposure to domestic violence and externalizing symptoms was significantly stronger for boys than for girls. Further analyses examining age, age by gender, and recruitment setting variables revealed no significant effects. Descriptive information obtained from this meta-analytic review suggests that more recent research within this area is beginning to address some of the significant methodological limitations of past research. Recommendations for future research in the area are discussed.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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