Tumor-associated and immunochemotherapy-dependent long-term alterations of the peripheral blood NK cell compartment in DLBCL patients

Natural Killer (NK) cells are a key component of tumor immunosurveillance and thus play an important role in rituximab-dependent killing of lymphoma cells via an antibody-dependent cellular cytotoxicity (ADCC) mechanism. We evaluated the phenotypic and functional assets of peripheral blood NK cell subsets in 32 newly-diagnosed diffuse large B-cell lymphoma (DLBCL) patients and in 27 healthy controls. We further monitored long-term modifications of patient NK cells for up to 12 months after rituximab-based immunochemotherapy. At diagnosis, patients showed a higher percentage of CD56dim and CD16C NK cells, and a higher frequency of GrzBC cells in CD56dim, CD56bright, and CD16C NK cell subsets than healthy controls. Conversely, DLBCL NK cell killing and interferon g (IFNg) production capability were comparable to those derived from healthy subjects. Notably, NK cells from refractory/relapsed patients exhibited a lower “natural” cytotoxicity. A marked and prolonged therapy-induced reduction of both “natural” and CD16- dependent NK cytotoxic activities was accompanied by the down-modulation of CD16 and NKG2D activating receptors, particularly in the CD56dim subset. However, reduced NK cell killing was not associated with defective lytic granule content or IFNg production capability. This study firstly describes tumor-associated and therapy-induced alterations of the systemic NK cell compartment in DLBCL patients. As these alterations may negatively impact rituximab-based therapy efficacy, our work may provide useful information for improving immunochemotherapeutic strategies

Randomised clinical trial: efficacy of a new synbiotic formulation containing Lactobacillus paracasei B21060 plus arabinogalactan and xilooligosaccharides in children with acute diarrhoea.

BACKGROUND: Acute diarrhoea is a frequent problem in children with heavy economic burden for families and society. AIM: To test the efficacy of a new synbiotic formulation containing Lactobacillus paracasei B21060, arabinogalactan and xilooligosaccharides in children with acute diarrhoea. METHODS: Double-blind, randomised, placebo-controlled trial, including children (age 3-36 m) with acute diarrhoea who were allocated to placebo or synbiotic group. Major outcome was resolution rate of diarrhoea at 72 h. Total duration of diarrhoea, daily stool outputs, stool consistency, working days lost by parents, adjunctive medications, and hospitalisation were also assessed. RESULTS: We enrolled 55 children in placebo group and 52 in synbiotic group. The two groups were similar for demographic and clinical characteristics. Resolution rate of diarrhoea at 72 h was significantly higher in synbiotic group (67%) compared to placebo group (40%, P = 0.005). Children in synbiotic group showed a significant reduction in the duration of diarrhoea (90.5 h, 78.1-102.9 vs. 109.8 h, 96.0-123.5, P = 0.040), daily stool outputs (3.3, 2.8-3.8 vs. 2.4, 1.9-2.8, P = 0.005) and stool consistency (1.3, 0.9-1.6 vs. 0.6, 0.4-0.9, P = 0.002) compared to placebo group (data expressed as mean, 95% CI). Rate of parents that missed at least one working day (41.8% vs. 15.4%, P = 0.003), rate of children that needed adjunctive medications (25.5% vs. 5.8%, P = 0.005) or hospitalisation (10.9% vs. 0%, P = 0.014) after the first 72 h of treatment, were reduced in synbiotic group. CONCLUSION: The synbiotic formulation studied is effective in children with acute diarrhoea. Australian New Zealand Clinical Trials Registry (ACTRN12611000641998)

Geodetic model of the 2016 Central Italy earthquake sequence inferred from InSAR and GPS data

We investigate a large geodetic data set of interferometric synthetic aperture radar (InSAR)and GPS measurements to determine the source parameters for the three main shocks of the 2016Central Italy earthquake sequence on 24 August and 26 and 30 October (Mw6.1, 5.9, and 6.5,respectively). Our preferred model is consistent with the activation of four main coseismic asperitiesbelonging to the SW dipping normal fault system associated with the Mount Gorzano-Mount Vettore-Mount Bove alignment. Additional slip, equivalent to aMw~ 6.1–6.2 earthquake, on a secondary (1) NEdipping antithetic fault and/or (2) on a WNW dipping low-angle fault in the hanging wall of the mainsystem is required to better reproduce the complex deformation pattern associated with the greatestseismic event (theMw6.5 earthquake). The recognition of ancillary faults involved in the sequencesuggests a complex interaction in the activated crustal volume between the main normal faults and thesecondary structures and a partitioning of strain releas

Preventive Effect of Cow's Milk Fermented with Lactobacillus paracasei CBA L74 on Common Infectious Diseases in Children: A Multicenter Randomized Controlled Trial

Background: Fermented foods have been proposed to prevent common infectious diseases (CIDs) in children attending day care or preschool

Scalable software framework for real-time data processing in the railway environment

Background: Ticks are obligate haematophagous ectoparasites of vertebrates and frequently parasitize avian species that can carry them across continents during their long-distance migrations. Ticks may have detrimental effects on the health state of their avian hosts, which can be either directly caused by blood-draining or mediated by microbial pathogens transmitted during the blood meal. Indeed, ticks host complex microbial communities, including bacterial pathogens and symbionts. Midichloria bacteria (Rickettsiales) are widespread tick endosymbionts that can be transmitted to vertebrate hosts during the tick bite, inducing an antibody response. Their actual role as infectious/pathogenic agents is, however, unclear. Methods: We screened for Midichloria DNA African ticks and blood samples collected from trans-Saharan migratory songbirds at their arrival in Europe during spring migration. Results: Tick infestation rate was 5.7%, with most ticks belonging to the Hyalomma marginatum species complex. Over 90% of Hyalomma ticks harboured DNA of Midichloria bacteria belonging to the monophylum associated with ticks. Midichloria DNA was detected in 43% of blood samples of avian hosts. Tick-infested adult birds were significantly more likely to test positive to the presence of Midichloria DNA than non-infested adults and second-year individuals, suggesting a long-term persistence of these bacteria within avian hosts. Tick parasitism was associated with a significantly delayed timing of spring migration of avian hosts but had no significant effects on body condition, whereas blood Midichloria DNA presence negatively affected fat deposits of tick-infested avian hosts. Conclusions: Our results show that ticks effectively transfer Midichloria bacteria to avian hosts, supporting the hypothesis that they are infectious to vertebrates. Bird infection likely enhances the horizontal spread of these bacteria across haematophagous ectoparasite populations. Moreover, we showed that Midichloria and tick parasitism have detrimental non-independent effects on avian host health during migration, highlighting the complexity of interactions involving ticks, their vertebrate hosts, and tick-borne bacteria

High prevalence of Trichomonas gallinae in wild columbids across western and southern Europe

Avian trichomonosis is known as a widespread disease in columbids and passerines, and recent findings have highlighted the pathogenic character of some lineages found in wild birds. Trichomonosis can affect wild bird populations including endangered species, as has been shown for Mauritian pink pigeons Nesoenas mayeri in Mauritius and suggested for European turtle doves Streptopelia turtur in the UK. However, the disease trichomonosis is caused only by pathogenic lineages of the parasite Trichomonas gallinae. Therefore, understanding the prevalence and distribution of both potentially pathogenic and non-pathogenic T. gallinae lineages in turtle doves and other columbids across Europe is relevant to estimate the potential impact of the disease on a continental scale