Bendamustine plus rituximab is an effective first-line treatment in hairy cell leukemia variant: A report of three cases

Hairy cell leukemia variant (HCLv) is a chronic lymphoproliferative disorder classified as a provisional entity in the 2016 WHO Classification of Lymphoid Tumors. HCLv is characterized by unfavorable prognosis, low complete remission rates and limited disease control following classical hairy cell leukemia-based regimens. In this study, we report 3 cases of elderly patients with treatment-naive, TP53 un-mutated HCLv, who were effectively treated with four cycles of bendamustine plus rituximab. The regimen was completed in all the patients with acceptable toxicity. All patients achieved a complete clinical response with no evidence of residual disease at bone marrow biopsy and flow-cytometry examination. After a median follow-up of 19 months, the 3 subjects are still in complete remission. In this work, bendamustine plus rituximab proved to be an effective and feasible first-line treatment strategy for elderly patients with TP53 un-mutated HCLv

Turning Away From Averted Gazes: The Effect of Social Exclusion on Gaze Cueing

Past studies showed increased sensitivity to other people’s gaze after social exclusion. In the present research, across two studies, we tested whether social exclusion could affect the basic cognitive phenomenon of gaze-cueing effect, namely, the tendency to redirect visual attention to the same location that other people are looking at. To this purpose, participants were socially excluded or included using the Cyberball manipulation. In Study 1, after the manipulation, participants performed a gaze-cueing task in which an individual’s gaze, oriented rightward or leftward, preceded a peripheral target stimulus requiring a simple categorization response. The gaze direction could be congruent or incongruent with the location of the target. Results revealed a reduced gaze-cueing effect for socially excluded than for socially included participants. In Study 2, where human gazes were replaced by arrow cues, such an interaction between social exclusion and trial congruency disappeared, indicating a specific effect of social stimuli. We interpreted these findings with the notion that excluded participants can perceive an averted gaze as a further sign of social exclusion, thus showing a reduced gaze-cueing effect

Depression, obesity and their comorbidity during pregnancy : effects on the offspring's mental and physical health

Depression and obesity represent two of the most common complications during pregnancy and are associated with severe health risks for both the mother and the child. Although several studies have analysed the individual effects of depression or obesity on the mothers and their children, the effects associated with the co-occurrence of both disorders have so far been poorly investigated. The relationship between depression and obesity is very complex and it is still unclear whether maternal depression leads to obesity or vice versa. It is well known that the intrauterine environment plays an important role in mediating the effects of both depression and obesity in the mother on the fetal programming, increasing the child's risk to develop negative outcomes.Peer reviewe

The Conundrum of Specifying very low Wave Overtopping Discharges

The design of certain seawalls / breakwaters has often been required to achieve very low targetovertopping discharges when these structures protect vulnerable infrastructure or activities. Thebalance between economically viable protection and performance requirements is often difficult toachieve without good knowledge on low overtopping. The paucity of data in this space and the highuncertainties associated with existing methods, increase the challenge. The occurrence of a lownumber of overtopping waves has the consequence that any test results are substantially moreaffected by the inherent variation of random waves, therefore more uncertain. The physical model testresults presented hereafter were successful in obtaining low to very low overtopping discharge data.For low / very low overtopping, these test data present considerable scatter relative to the latestempirical prediction. A number of repetitions was performed for conditions giving very low overtoppingdischarges, which illustrated the inherent uncertainty associated with low overtopping

Cerebellar Transcranial Direct Current Stimulation (tDCS), Leaves Virtual Navigation Performance Unchanged

Spatial cognition is an umbrella term used to refer to the complex set of abilities necessary to encode, categorize, and use spatial information from the surrounding environment to move effectively and orient within it. Experimental studies indicate that the cerebellum belongs to the neural network involved in spatial cognition, although its exact role in this function remains unclear. Our aim was to investigate in a pilot study using a virtual reality navigation task in healthy subjects whether cerebellar transcranial direct current stimulation (tDCS), a non-invasive technique, influences spatial navigation. Forty healthy volunteers (24 women; age range = 20–42 years; years of education range 13–18) were recruited. The virtual reality spatial navigation task comprised two phases: encoding, in which participants actively navigated the environment and learned the spatial locations for one object, and retrieval, in which they retrieved the position of the object they had discovered and memorized in the previous encoding phase, starting from another starting point. Participants received tDCS stimulation (anodal or sham according to the experimental condition they were assigned to) for 20 min before beginning the retrieval phase. Our results showed that cerebellar tDCS left the accuracy of the three indexes used to measure effective navigational abilities unchanged. Hence, cerebellar tDCS had no influence on the retrieval phase for the spatial maps stored. Further studies, enrolling a larger sample and testing a different stimulation protocol, may give a greater insight into the role of the cerebellum in spatial navigation

BDNF Val66Met polymorphism and protein levels in Amniotic Fluid

Brain-Derived Neurotrophic Factor (BDNF) is a neurotrophin which plays survival- and growth-promoting activity in neuronal cells and it is involved in cellular plasticity mechanisms as it controls activity dependent synaptic transmission. A functional polymorphism (Val66Met) in the pro-region of BDNF, which affects the intracellular trafficking of proBDNF has been associated with memory and cognitive deficits as well as to an increased susceptibility for several psychiatric disorders especially those with a neurodevelopmental origin. To date, no study has evaluated the influence of the Val66Met polymorphism on BDNF levels in a peripheral system that may reflect fetal neurodevelopment. Therefore we investigated in amniotic fluids (AF) obtained from 139 healthy women during 15-17 week of pregnancy, BDNF protein levels in correlation with the Val66Met polymorphism

Bdnf-Nrf-2 crosstalk and emotional behavior are disrupted in a sex-dependent fashion in adolescent mice exposed to maternal stress or maternal obesity

Maternal obesity has been recognized as a stressor affecting the developing fetal brain, leading to long-term negative outcomes comparable to those resulting from maternal psychological stress, although the mechanisms have not been completely elucidated. In this study, we tested the hypothesis that adverse prenatal conditions as diverse as maternal stress and maternal obesity might affect emotional regulation and stress response in the offspring through common pathways, with a main focus on oxidative stress and neuroplasticity. We contrasted and compared adolescent male and female offspring in two mouse models of maternal psychophysical stress (restraint during pregnancy - PNS) and maternal obesity (high-fat diet before and during gestation - mHFD) by combining behavioral assays, evaluation of the hypothalamic-pituitary-adrenal (HPA) axis reactivity, immunohistochemistry and gene expression analysis of selected markers of neuronal function and neuroinflammation in the hippocampus, a key region involved in stress appraisal. Prenatal administration of the antioxidant N-acetyl-cysteine (NAC) was used as a strategy to protect fetal neurodevelopment from the negative effects of PNS and mHFD. Our findings show that these two stressors produce overlapping effects, reducing brain anti-oxidant defenses (Nrf-2) and leading to sex-dependent impairments of hippocampal Bdnf expression and alterations of the emotional behavior and HPA axis functionality. Prenatal NAC administration, by restoring the redox balance, was able to exert long-term protective effects on brain development, suggesting that the modulation of redox pathways might be an effective strategy to target common shared mechanisms between different adverse prenatal conditions

Thyrospheres from B-CPAP cell line with BRAF and TERT promoter mutations have different functional and molecular features than parental cells

Human thyroid cancer derived cell lines are widely used to study the mechanisms involved in thyroid carcinogenesis. However, there is limited availability of non-cross-contaminated cancer cell lines derived from papillary thyroid carcinoma (PTC), and the B-CPAP cell line is one of the few such lines. B-CPAP cells have been genetically and cytogenetically well-characterized, but details of their stemness features remain uncertain. Considering that this cell line is extensively used for in vitro studies on thyroid tumorigenesis, we broaden its functional and molecular profiles as well as the tumorigenic capacity. We used functional assays (sphere-forming capacity and efficiency), assessed self-renewal and propagation efficiency and tested in vivo tumorigenicity in Hsd:Athymic Nude-Foxn1nu mice. Expression of markers of stemness, differentiation, and epithelial-mesenchymal transition were estimated at RNA and protein levels in adherent parental cells and sphere-forming cells. Functional aspects and stemness features were compared with normal thyrocytes. Protein expression of xenograft tumors was evaluated by immunohistochemistry. B-CPAP sphere-forming cells were able to form thyrospheres theoretically indefinitely in an appropriate serum-free medium, reverting to the adherent parental cell phenotype when cultured in differentiation medium. Different expression of ALDH1-A1 and CD44 stemness markers and TTF-1 and CK19 differentiation markers allowed discrimination between isolated sphere-forming cells and adherent parental cells, indicating that sphere-forming cells retained stem-like features. In keeping with these observations, tumorigenicity assays confirmed that, relative to parental adherent cells, thyrospheres had enhanced capacity to initiate xenograft tumors. Thyrospheres from normal cell line retained very low functional capacity, as well as different stemness markers expression compared to tumor thyrospheres. Our findings may constitute a useful background to develop an in vitro model for assessing the origin and progression of papillary thyroid carcinoma bearing BRAFV600E and TERT promoter mutations

Autism and neurodevelopmental disorders: the Sars-Cov-2 pandemic implications

The Special Issue (SI) “Autism and Neurodevelopmental Disorders: The SARS-CoV-2 Pandemic Implications” is an interesting project that adopted a scientific point of view with important implications in clinical and practical fields [...

The Effect of Curcumin on Idiopathic Parkinson Disease: A Clinical and Skin Biopsy Study

There are currently no standardized therapies for Parkinson disease (PD). Curcumin shows anti-amyloidogenic properties in vitro and may be a promising treatment for PD. We evaluated the effects of curcumin supplementation on clinical scales and misfolded, phosphorylated α-synuclein (p-syn) accumulation in skin biopsies in 19 PD patients who received curcumin supplementation for 12 months and 14 PD patients to treated with curcumin. The patients underwent autonomic (COMPASS-31), motor (MDS-UPDRS and H&Y) and nonmotor (NMSS) questionnaires and skin biopsies to evaluate clinical involvement and p-syn load in skin nerves at the beginning and the end of study. Curcumin and curcuminoid levels were assayed in plasma and CSF. Supplemented patients showed detectable CSF curcuminoid levels that were lower than those in plasma. They showed a decrease of COMPASS-31 and NMSS scores, and a slight p-syn load decrease versus untreated patients who displayed a worsening of these parameters despite increased levodopa doses. Multiple regression models showed a significant effect of curcumin supplementation in decreasing the worsening of the clinical parameters and p-syn load at after curcumin treatment. These data suggest that curcumin can cross the blood-brain barrier, that it is effective in ameliorating clinical parameters and that it shows a tendency to decrease skin p-syn accumulation in PD patients