Internet addiction and related clinical problems: a study on italian young adults

The considerable prominence of internet addiction (IA) in adolescence is at least partly explained by the limited knowledge thus far available on this complex phenomenon. In discussing IA, it is necessary to be aware that this is a construct for which there is still no clear definition in the literature. Nonetheless, its important clinical implications, as emerging in recent years, justify the lively interest of researchers in this new form of behavioral addiction. Over the years, studies have associated IA with numerous clinical problems. However, fewer studies have investigated what factors might mediate the relationship between IA and the different problems associated with it. Ours is one such study. The Italian version of the SCL-90 and the IAT were administered to a sample of almost 800 adolescents aged between 16 and 22 years. We found the presence of a significant association between IA and two variables: somatization (\u3b2 = 7.80; p < 0.001) and obsessive-compulsive symptoms (\u3b2 = 2.18; p < 0.05). In line with our hypothesis, the results showed that somatization predicted the relationship between obsessive-compulsive symptoms and IA (\u3b2 = -2.75; t = -3.55; p < 0.001), explaining 24.5% of its variance (\u394R2 = 1.2%; F = 12.78; p < 0.01). In addition, simple slopes analyses revealed that, on reaching clinical significance (+1 SD), somatization showed higher moderation effects in the relationship between obsessive-compulsive symptoms and IA (\u3b2 = 6.13; t = 7.83; p < 0.001). These results appear to be of great interest due to the absence of similar evidence in the literature, and may open the way for further research in the IA field. Although the absence of studies in the literature does not allow us to offer an exhaustive explanation of these results, our study supports current addiction theories which emphasize the important function performed by the enteroceptive system, alongside the more cited reflexive and impulsive systems

Innate Lymphoid Cells: Expression of PD-1 and Other Checkpoints in Normal and Pathological Conditions

Innate lymphoid cells (ILCs) belong to a family of immune cells. Recently, ILCs have been classified into five different groups that mirror the function of adaptive T cell subsets counterparts. In particular, NK cells mirror CD8+ cytotoxic T cells while ILC1, ILC2, ILC3, and Lymphoid tissue inducer (LTi)-like cells reflect the function of CD4+T helper (Th) cells (Th1, Th2, and Th17 respectively). ILCs are involved in innate host defenses against pathogens and tumors, in lymphoid organogenesis, and in tissue remodeling/repair. In recent years, important molecular inducible checkpoints (PD-1, TIM3, and TIGIT) were shown to control/inactivate different immune cell types. The expression of many of these receptors has been detected on NK cells and subsets of tissue-resident ILCs in both physiological and pathological conditions, including cancer. In particular, it has been demonstrated that the interaction between PD-1+ immune cells and PD-L1/PD-L2+ tumor cells may compromise the anti-tumor effector function leading to tumor immune escape. However, while the effector function of NK cells in tumor is well-established, limited information exists on the other ILC subsets. We will summarize what is known to date on the expression and function of these checkpoint receptors on NK cells and ILCs, with a particular focus on the recent data that reveal an essential contribution of the blockade of PD-1 and TIGIT on NK cells to the immunotherapy of cancer. A better information regarding the presence and the function of different ILCs and of the inhibitory checkpoints in pathological conditions may offer important clues for the development of new immune therapeutic strategies

Human natural killer cells and other innate lymphoid cells in cancer: Friends or foes?

Innate lymphoid cells (ILC) including NK cells (cytotoxic) and the recently identified "helper" ILC1, ILC2 and ILC3, play an important role in innate defenses against pathogens. Notably, they mirror analogous T cell subsets, regarding the pattern of cytokine produced, while the timing of their intervention is few hours vs days required for T cell-mediated adaptive responses. On the other hand, the effectiveness of ILC in anti-tumor defenses is controversial. The relevance of NK cells in the control of tumor growth and metastasis has been well documented and they have been exploited in the therapy of high risk leukemia in the haploidentical hematopoietic stem cell transplantation setting. In contrast, the actual involvement of helper ILCs remains contradictory. Thus, while certain functional capabilities of ILC1 and ILC3 may favor anti-tumor responses, other functions could rather favor tumor growth, neo-angiogenesis, epithelial-mesenchymal transition and metastasis. In addition, ILC2, by secreting type-2 cytokines, are thought to induce a prevalent pro-tumorigenic effect. Finally, the function of both NK cells and helper ILCs may be inhibited by the tumor microenvironment, thus adding further complexity to the interplay between ILC and tumors

PD-1 in human NK cells: evidence of cytoplasmic mRNA and protein expression

Under physiological conditions, PD-1/PD-L1 interactions regulate unwanted over-reactions of immune cells and contribute to maintain peripheral tolerance. However, in tumor microenvironment, this interaction may greatly compromise the immune-mediated anti-tumor activity. PD-1 + NK cells have been detected in high percentage in peripheral blood and ascitic fluid of ovarian carcinoma patients. To acquire information on PD-1 expression and physiology in human NK cells, we analyzed whether PD-1 mRNA and protein are present in resting, surface PD-1 12 , NK cells from healthy donors. Both different splicing isoforms of PD-1 mRNA and a cytoplasmic pool of PD-1 protein were detected. Similar results were obtained also from both in vitro-activated and tumor-associated NK cells. PD-1 mRNA and protein were higher in CD56 dim than in CD56 bright NK cells. Confocal microscopy analyses revealed that PD-1 protein is present in virtually all NK cells analyzed. The present findings are compatible with a rapid surface expression of PD-1 in NK cells in response to appropriate, still undefined, stimuli

Bottom current-controlled quaternary sedimentation at the foot of the Malta Escarpment (Ionian Basin, Mediterranean)

A better understanding of the evolution of bottom current circulation and associated deposits is significant for many applications including paleoclimatology and geological hazard. Besides the large contourite drifts, bottom currents may generate fields of large sediment waves that, depending on their height and velocity of migration, may pose severe risk for infrastructures. Conversely, the time span of their paleoceanographic record is generally relatively short. We use bathymetry data, sub-bottom and seismic reflection profiles and legacy oceanographic data to analyze the sediment waves occurring in a deep environment (from 2400 to 3800 m water depth at the foot of the Malta Escarpment in the Mediterranean Sea) to understand their evolution in time, their significance for paleoceanography, and their relation to present day hydrographic conditions. In the absence of direct stratigraphic information, we use the information from nearby studies and from ODP Site 964 and DSDP Site 374 to constrain the age of the sedimentary successions. We discover that these waves (about 2.5 km in wavelength, 50 m in height, with crest sub-perpendicular to the continental slope trend) have been steadily growing and migrating northward since about 500 ka, although an irregular growth and unsteady migration is distinguishable since about 1800 ka. The waves are generated by predominantly alongslope southward flowing bottom currents compatible with modern hydraulic conditions (mean flow speed of ~5 cm s−1, peaks of 15 cm s−1). The rate of crest migration (~ 2.0–3.2 mm a−1) and the average sedimentation rate (0.64–0.69 mm a−1) are unusually high for deep sea environments away from turbidity currents paths. We infer that the steady development of sediment waves is produced by a drastic increase in sediment input to the Ionian Basin resulting from the tectonic uplift in NE Sicily and Calabria and the onset of a relatively steady, low energy bottom current regime following the Mid-Pleistocene Transition. We attempt to extract information on orbital cyclicity preserved in the seismic record from the power spectra of virtual seismic traces from the well preserved succession of 5 visually discernible, regularly spaced sub-units consisting of alternation of high-amplitude and low-reflectivity packages within the last 500 ka. Peaks in the power spectra can be identified around orbital obliquity and precession periodicities, while eccentricity appears not to be recorded. We discuss the results of seismic cyclicity analysis relative to uncertainties of stratigraphic and petrophysical constraints. The sediment waves along the foot of the Malta escarpment are an excellent candidate for the extraction of a long, continuous and high resolution sedimentary record of the paleo circulation changes and climate cycles in the Mediterranean Sea since about 500 ka.peer-reviewe

Human Innate Lymphoid Cells: Their Functional and Cellular Interactions in Decidua

Innate lymphoid cells (ILC) are developmentally related cell subsets that play a major role in innate defenses against pathogens, in lymphoid organogenesis and in tissue remodeling. The best characterized ILC are natural killer (NK) cells. They are detectable in decidua in the early phases of pregnancy. During the first trimester, NK cells represent up to 50% of decidua lymphocytes. Differently from peripheral blood (PB) NK cells, decidual NK (dNK) cells are poorly cytolytic, and, instead of IFNγ, they release cytokines/chemokines that induce neo-angiogenesis, tissue remodeling, and placentation. dNK interact with resident myeloid cells and participate in the induction of regulatory T cells that play a pivotal role in maintaining an efficient fetal–maternal tolerance. dNK cells may originate from CD34+ precursor cells present in situ and/or from immature NK cells already present in endometrial tissue and/or from PB NK cells migrated to decidua. In addition to NK cells, also ILC3 are present in human decidua during the first trimester. Decidual ILC3 include both natural cytotoxic receptor (NCR)+ and NCR− cells, producing respectively IL-8/IL-22/GM-CSF and TNF/IL-17. NCR+ILC3 have been shown to establish physical and functional interactions with neutrophils that, in turn, produce factors that are crucial for pregnancy induction/maintenance and for promoting the early inflammatory phase, a fundamental process for a successful pregnancy. While NCR+ILC3 display a stable phenotype, most of NCR−ILC3 may acquire phenotypic and functional features of NCR+ILC3. In conclusion, both NK cells and ILC3 are present in human decidua and may establish functional interactions with immune and myeloid cells playing an important role both in innate defenses and in tissue building/remodeling/placentation during the early pregnancy. It is conceivable that altered numbers or function of these cells may play a role in pregnancy failure

Critical COVID-19 Patients Through First, Second And Third Wave: Retrospective Observational Study Comparing Outcomes In ICU.

Introduction- The time-course of the COVID-19 pandemic was characterized by subsequent waves identified by peaks of Intensive Care Unit (ICU) admission rates. During these periods, progressive knowledge of the disease led to the development of specific therapeutic strategies. This retrospective study investigates whether this led to improvement in outcomes of COVID-19 patients admitted to ICU. Methods- Outcomes were evaluated in consecutive adult COVID19 patients admitted to our ICU, divided into three waves based on the admission period: the first wave from February 25th, 2020, to July 6th, 2020; the second wave from September 20th, 2020, to February 13th, 2021; the third wave from February 14th, 2021 to April 30th, 2021. Differences were assessed comparing outcomes and by using different multivariable Cox models adjusted for variables related to outcome. Further sensitivity analysis was performed in patients undergoing invasive mechanical ventilation. Results- Overall, 428 patients were included in the analysis: 102, 169 and 157 patients in the first, second and third wave. The ICU and in-hospital crude mortalities were lower by 7% and 10% in the third wave compared to the other 2 waves (p>0.05). A higher number of ICU and hospital free days at day 90 was found in the third wave when compared to the other 2 waves (p=0.001). Overall, 62.6% underwent invasive ventilation, with decreasing requirement during the waves (p=0.002). The adjusted Cox model showed no difference in the Hazard Ratio for mortality among the waves. In the propensity-matched analysis the hospital mortality rate was reduced by 11% in the third wave (p=0.044). Conclusions - With application of best practice as known by the time of the first three waves of the pandemic, our study failed to identify a significant improvement in mortality rate when comparing the different waves of the COVID-19 pandemic, notwithstanding, the sub-analyses showed a trend in mortality reduction in the third wave. Rather, our study identified a possible positive effect of dexamethasone on mortality rate reduction and the increased risk of death related to bacterial infections in the three waves

Killer Ig-Like Receptors (KIRs): Their Role in NK Cell Modulation and Developments Leading to Their Clinical Exploitation

Natural killer (NK) cells contribute to the first line of defense against viruses and to the control of tumor growth and metastasis spread. The discovery of HLA class I specific inhibitory receptors, primarily of killer Ig-like receptors (KIRs), and of activating receptors has been fundamental to unravel NK cell function and the molecular mechanisms of tumor cell killing. Stemmed from the seminal discoveries in early '90s, in which Alessandro Moretta was the major actor, an extraordinary amount of research on KIR specificity, genetics, polymorphism, and repertoire has followed. These basic notions on NK cells and their receptors have been successfully translated to clinical applications, primarily to the haploidentical hematopoietic stem cell transplantation to cure otherwise fatal leukemia in patients with no HLA compatible donors. The finding that NK cells may express the PD-1 inhibitory checkpoint, particularly in cancer patients, may allow understanding how anti-PD-1 therapy could function also in case of HLA class Ineg tumors, usually susceptible to NK-mediated killing. This, together with the synergy of therapeutic anti-checkpoint monoclonal antibodies, including those directed against NKG2A or KIRs, emerging in recent or ongoing studies, opened new solid perspectives in cancer therapy

MY Camelopardalis, a very massive merger progenitor

Context. The early-type binary MY Cam belongs to the young open cluster Alicante 1, embedded in Cam OB3. Aims. MY Cam consists of two early-O type main-sequence stars and shows a photometric modulation suggesting an orbital period slightly above one day. We intend to confirm this orbital period and derive orbital and stellar parameters. Methods. Timing analysis of a very exhaustive (4607 points) light curve indicates a period of 1.1754514 +- 0.0000015 d. High- resolution spectra and the cross-correlation technique implemented in the TODCOR program were used to derive radial velocities and obtain the corresponding radial velocity curves for MY Cam. Modelling with the stellar atmosphere code FASTWIND was used to obtain stellar parameters and create templates for cross-correlation. Stellar and orbital parameters were derived using the Wilson-Devinney code, such that a complete solution to the binary system could be described. Results. The determined masses of the primary and secondary stars in MY Cam are 37.7 +- 1.6 and 31.6 +- 1.4 Msol, respectively. The corresponding temperatures, derived from the model atmosphere fit, are 42 000 and 39 000 K, with the more massive component being hotter. Both stars are overfilling their Roche lobes, sharing a common envelope. Conclusions. MY Cam contains the most massive dwarf O-type stars found so far in an eclipsing binary. Both components are still on the main sequence, and probably not far from the zero-age main sequence. The system is a likely merger progenitor, owing to its very short period.Comment: 8 pages, 6 figures, photometric data available on-line, Astronomy and Astrophysics, 201