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Inhibitory control is a main component of executive functions that relate to the ability to control prepotent responses and to resist interferences. Deficits in inhibitory control have been associated with numerous disorders, but exercise has become a promising approach to benefit this domain. This systematic review and meta-analysis aims to provide synthesized information and effect size calculations of the benefits of chronic exercise interventions on the inhibitory control of healthy children and adolescents. A systematic search of PubMed, PsycINFO, MEDLINE, ERIC, SPORTDiscus, and PsycArticles identified 4166 articles to be screened for eligibility. A total of 10 studies (3138 participants) met the inclusion criteria. A random-effects analysis model was performed in three variables: accuracy, reaction time and combined scores. The results showed a very small but statistically significant effect in accuracy (d = 0.14, 95% CI 0.01 to 0.27, P =.04), and two almost null effects (statistically non-significant), in the reaction time (d = 0.03, 95% CI -0.10 to 0.16, P =.62) and the combined scores (d = 0.06, 95% CI -0.03 to 0.15, P =.17). Despite the high number of studies that reported positive outcomes, this meta-analysis found only modest benefits in the inhibitory control of healthy children and adolescents after they participated in different chronic exercise interventions. The strict inclusion criteria of this study and the high variability in the designs of the exercise interventions included, among other reasons, might explain the obtained results.

Background The functional profile of cytomegalovirus (CMV)-specific CD8+ T cells that associate with protection from and control of CMV DNAemia in allogeneic stem cell transplant (allo-SCT) recipients remains incompletely characterized. Methods We enumerated pp65 and immediate early (IE)-1-specific CD8+ T cells expressing interferon-gamma, tumor necrosis factor-alpha, and CD107a, by flow cytometry in 94 patients at days +30 and +60 after allo-SCT. Results Fifty of 94 patients had CMV DNAemia within the first 100 days after transplant. CMV-specific CD8+ T-cell responses (of any functional type) were more likely to be detected in patients who did not display CMV DNAemia than in those who did (P = 0.04). Qualitatively, no major differences in the functional signature of CMV-specific CD8+ T cells were noted between patients who had or did not have CMV DNAemia. Patients displaying levels of polyfunctional CD8+ T cells at day +30 >0.30 cell/μL had a lower risk of CMV DNAemia (positive predictive value 76%, and negative predictive value 43%). Conclusion The presence of polyfunctional CD8+ T cells (either expressing CD107a or not) was associated with lower levels of CMV replication, and higher frequency of self-resolved episodes. The data reported further clarify the role of polyfunctional CD8+ T cells in control of CMV DNAemia in allo-SCT recipients.

The role of Natural killer (NK) cells in the control of cytomegalovirus (CMV) infection in allogeneic stem cell transplant recipients has not been precisely characterized. The current study is aimed at investigating the potential role of NK cells expressing the activating receptor NKG2C in affording protection against the development of CMV DNAemia in patients exhibiting detectable CMV-specific CD8+ T-cell responses early following transplantation. A total of 61 nonconsecutive patients were included in the study. Peripheral levels of CD56brightCD16−/low and CD56dimCD16+ NKG2C+ NK cells and CMV pp65/IE-1-specific IFN-γ-producing CD8+ T-cells were enumerated by flow cytometry at days +30 and +60 after transplant. Neither the absolute number of NKG2C+ NK cells, nor that of CD56brightCD16−/low and CD56dimCD16+ NKG2C+ NK-cell subsets at day 30 differed significantly between patients with or without subsequent CMV DNAemia. No significant correlation was found between levels of both NKG2C+ NK-cell populations and the peak CMV DNA load within subsequent episodes of CMV DNAemia. The data indicate that enumeration of NKG2C+ NK cells early after transplant is unlikely to be helpful in identifying those patients at highest risk of developing CMV DNAemia. Moreover, the data do not support a direct implication of NKG2C+ NK cells in preventing the development of CMV DNAemia. J. Med. Virol. 87:1601–1607, 2015. © 2015 Wiley Periodicals, Inc.

Single nucleotide polymorphisms (SNPs) in genes involved in the activation or regulation of innate and adaptive immune responses may modulate the susceptibility to and the natural history of certain chronic viral infections. The current study aimed to investigate whether donor and recipient SNPs in the chemokine receptor 5 (rs1800023), monocyte chemoattractant protein 1 (rs13900), interleukin-10 (rs1878672), and Toll-like receptor 9 (rs352140) genes would exert any influence on the rate of incidence and features of CMV DNAemia in the allogeneic stem cell transplantation setting. This was a retrospective observational multicenter study. The cohort consisted of 102 non-consecutive allogeneic stem cell transplant recipients. SNP genotyping was performed by allele-specific real-time PCR. CMV surveillance was performed by the pp65 antigenemia assay/and or by real-time PCR. Seventy-three patients developed CMV DNAemia within the first 100 days after transplantation (71.5%). Neither donor nor recipient SNPs were associated significantly with the rate of incidence of active CMV infection, nor with the need for pre-emptive antiviral therapy. Both the duration of CMV DNAemia and the plasma CMV DNA peak load during episodes were significantly higher in patients harboring the donor (but not the recipient) chemokine receptor 5 A/A genotype, than in their A/G and G/G counterparts (P = 0.022 and P = 0.045, respectively). The data reported suggest that SNPs in chemokine receptor 5 may influence the dynamics of CMV infection in the Allo-SCT setting. J. Med. Virol. 87:248–255, 2015. © 2014 Wiley Periodicals, Inc.

The role of natural killer (NK) cells in affording protection against human cytomegalovirus (CMV) in allogeneic stem cell transplant recipients is largely unknown. The current study was aimed at determining whether NKG2C+ NK cells confer protection from CMV DNAemia early following transplantation in patients lacking mono and polyfunctional CMV pp65 and IE-1-specific CD4+ and CD8+ T-cell responses, as measured by flow cytometry for intracellular cytokine staining. Fourteen out of the 36 patients included in this study developed CMV DNAemia between days +30 and +60 after transplant. Three patients did so after day +60. Peripheral blood levels of CD56(bright) CD16(-/low) and CD56(dim) CD16+ NKG2C+ NK cells measured at day +30 and at day +60 in patients who had or had not subsequent CMV DNAemia did not differ significantly. In addition, no significant correlation was found between CD56(bright) CD16(-/low) (σ = -0.229; P = 0.39) and CD56(dim) CD16+ (σ = -0.285; P = 0.28) NKG2C+ NK-cell levels and initial plasma CMV DNA loads. In summary, the data presented do not support a direct implication of NKG2C+ NK cells in preventing the development of CMV DNAemia or modulating the magnitude of CMV replication at early stages during episodes of CMV DNAemia in allogeneic stem cell transplant patients with unreconstituted CMV-specific T-cell responses.

The coexistence of skin-limited Langerhans cell histiocytosis (LCH) and Rosai-Dorfman disease (RDD) is an exceptional finding. The association of lymphomas and histiocytosis is also infrequent. We report the case of a 68-year-old man which presented an exceptional association of cutaneous LCH and RDD and splenic marginal zone lymphoma. He was stable for few years. Suddenly, the patient was admitted into Hematology Department with a remarkable enlargement of spleen and liver without enlargement of lymphadenopathies or skin lesions flare. He died 24 h later despite treatment with systemic chemotherapy combined with prednisone. Pre-mortem biopsy showed infiltration with histiocytic sarcoma. We think that a transdifferentiation phenomenon could explain our case, although we could not show a clonal relationship between the cutaneous and the liver diseases. We also want to pay attention to the fact that a fast transformation to a more aggressive disease can occur long time after the presentation of the first lesion, a problem that stresses the importance of performing a close and permanent follow-up of these patients.

Immune mechanisms involved in control of cytomegalovirus (CMV) infection in the allogeneic stem cell transplantation setting have not been fully disclosed. CMV pp65 and IE-1-specific CD8(+) T cells expressing IFN-γ, TNF-α, and CD107a, alone or in combination, and NKG2C(+) NK cells were prospectively enumerated during 13 episodes of CMV DNAemia. The expansion of monofunctional and polyfunctional CD8(+) T cells was associated with CMV DNAemia clearance. The size and functional diversity of the expanding CD8(+) T-cell population was greater in self-resolved episodes than in episodes treated with antivirals. These differences were related to the magnitude of expansion of cognate antigen IFN-γ CD4(+) T cells. The resolution of CMV DNAemia was associated frequently with a marked expansion of both CD56(dim) /CD16(+) NK cells and NKG2C(+) CD56(bright) /CD16(-) NK cells. The data lend support to the role of polyfunctional CD8(+) T cells in controlling CMV replication in the allogeneic stem cell transplantation setting, and suggest that NKG2C(+) NK cells may be involved critically in the resolution of CMV DNAemia episodes.

Summary. Thrombosis is a rare complication in patients with congenital clotting factor deficiencies. In most cases, it is related to inherited procoagulant factors, use of central venous catheters or administration of coagulation factor concentrates. There are only a few case reports about thrombotic events during treatment with fresh frozen plasma (FFP). We report the case of a patient with homozygous inherited factor V deficiency, who developed a pulmonary embolism at a time of treatment with methylene blue treated FFP (MBFFP). The patient had only two other factors predisposing to thrombosis and both were acquired: obesity and bed rest. He started anticoagulant treatment with low molecular weight heparin (LMWH) while the deficient factors were replaced with MBFFP. After 8 days of treatment the patient developed a severe respiratory insufficiency. Pulmonary haemorrhage was considered among the differential diagnosis and LMWH was stopped. An inferior vena cava filter was placed without any further thrombotic complications. To our knowledge, there are no reports about patients with clotting factor deficiencies who developed a thrombotic event during treatment with MBFFP.