Differential physiological changes following internet exposure in higher and lower problematic internet users

Problematic internet use (PIU) has been suggested as in need of further research with a view to being included as a disorder in future Diagnostic and Statistical Manual (DSM) of the American Psychiatric Association, but lack of knowledge about the impact of internet cessation on physiological function remains a major gap in knowledge and a barrier to PIU classification. One hundred and forty-four participants were assessed for physiological (blood pressure and heart rate) and psychological (mood and state anxiety) function before and after an internet session. Individuals also completed a psychometric examination relating to their usage of the internet, as well as their levels of depression and trait anxiety. Individuals who identified themselves as having PIU displayed increases in heart rate and systolic blood pressure, as well as reduced mood and increased state of anxiety, following cessation of internet session. There were no such changes in individuals with no self-reported PIU. These changes were independent of levels of depression and trait anxiety. These changes after cessation of internet use are similar to those seen in individuals who have ceased using sedative or opiate drugs, and suggest PIU deserves further investigation and serious consideration as a disorder

Home-based palliative approach for people with severe multiple sclerosis and their carers: Study protocol for a randomized controlled trial

Background: Preliminary evidence suggests that palliative care may be useful for people with severe multiple sclerosis (MS). The aim of this study is to determine the effectiveness of a home-based palliative approach (HPA) for people with severe MS and their carers. Methods/design: This is a single-blind randomized controlled trial with a nested qualitative study. Seventy-five severe MS-carer dyads are being randomized (at three centers, one in each area of Italy) to HPA or usual care (UC) in a 2:1 ratio. Each center has a specially trained team consisting of four professionals (physician, nurse, psychologist, social worker). The team makes a comprehensive assessment of the needs of the dyads. HPA content is then agreed on, discussed with the patient's caring physician, and delivered over six months. The intervention is not intended to replace existing services. At later visits, the team checks the HPA delivery and reviews/modifies it as necessary. Discussion: The results of our study will show whether the HPA is feasible and beneficial to people with severe MS and their carers living in the three Italian geographic areas. The nested qualitative study will add to the understanding of the strengths and limitations of the intervention

Rationale and design of an independent randomised controlled trial evaluating the effectiveness of aripiprazole or haloperidol in combination with clozapine for treatment-resistant schizophrenia

<p>Abstract</p> <p>Background</p> <p>One third to two thirds of people with schizophrenia have persistent psychotic symptoms despite clozapine treatment. Under real-world circumstances, the need to provide effective therapeutic interventions to patients who do not have an optimal response to clozapine has been cited as the most common reason for simultaneously prescribing a second antipsychotic drug in combination treatment strategies. In a clinical area where the pressing need of providing therapeutic answers has progressively increased the occurrence of antipsychotic polypharmacy, despite the lack of robust evidence of its efficacy, we sought to implement a pre-planned protocol where two alternative therapeutic answers are systematically provided and evaluated within the context of a pragmatic, multicentre, independent randomised study.</p> <p>Methods/Design</p> <p>The principal clinical question to be answered by the present project is the relative efficacy and tolerability of combination treatment with clozapine plus aripiprazole compared with combination treatment with clozapine plus haloperidol in patients with an incomplete response to treatment with clozapine over an appropriate period of time. This project is a prospective, multicentre, randomized, parallel-group, superiority trial that follow patients over a period of 12 months. Withdrawal from allocated treatment within 3 months is the primary outcome.</p> <p>Discussion</p> <p>The implementation of the protocol presented here shows that it is possible to create a network of community psychiatric services that accept the idea of using their everyday clinical practice to produce randomised knowledge. The employed pragmatic attitude allowed to randomly allocate more than 100 individuals, which means that this study is the largest antipsychotic combination trial conducted so far in Western countries. We expect that the current project, by generating evidence on whether it is clinically useful to combine clozapine with aripiprazole rather than with haloperidol, provides physicians with a solid evidence base to be directly applied in the routine care of patients with schizophrenia.</p> <p>Trial Registration</p> <p><b>Clincaltrials.gov Identifier</b>: NCT00395915</p

Genome-wide Analyses Identify KIF5A as a Novel ALS Gene

To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.Peer reviewe

Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology

A cross-ancestry genome-wide association meta-analysis of amyotrophic lateral sclerosis (ALS) including 29,612 patients with ALS and 122,656 controls identifies 15 risk loci with distinct genetic architectures and neuron-specific biology. Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a lifetime risk of one in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry genome-wide association study (GWAS) including 29,612 patients with ALS and 122,656 controls, which identified 15 risk loci. When combined with 8,953 individuals with whole-genome sequencing (6,538 patients, 2,415 controls) and a large cortex-derived expression quantitative trait locus (eQTL) dataset (MetaBrain), analyses revealed locus-specific genetic architectures in which we prioritized genes either through rare variants, short tandem repeats or regulatory effects. ALS-associated risk loci were shared with multiple traits within the neurodegenerative spectrum but with distinct enrichment patterns across brain regions and cell types. Of the environmental and lifestyle risk factors obtained from the literature, Mendelian randomization analyses indicated a causal role for high cholesterol levels. The combination of all ALS-associated signals reveals a role for perturbations in vesicle-mediated transport and autophagy and provides evidence for cell-autonomous disease initiation in glutamatergic neurons

L’esame radiologico del Lap-Band nel trattamento della grave obesità

Lo scopo di questo lavoro è quello di stabilire il ruolo della radio - logia nel controllo dei pazienti sottoposti ad intervento di bendaggio gastrico per il trattamento della obesità patologica e di valutare i dif - ferenti tipi di complicanze che ne possono derivare. Sono stati esaminati 43 pazienti prima e dopo intervento di ben - daggio gastrico. In tutti i pazienti l’esame radiologico ha permesso di valutare il posizionamento del dispositivo, le dimensioni della camera gastrica e dello stoma. In alcuni casi è stato possibile modificare il calibro dello stoma sotto controllo fluoroscopico. Il 74,4% dei pazienti ha ottenuto un adeguato calo ponderale in assenza di complicanze. Nel 16,2% il risultato è stato insoddisfacente e gli esami radiologici hanno mostrato la presenza di differenti tipi di complicanze. Nel 9,3% dei pazienti non è stato ottenuto un calo ponderale soddisfacente, nonostante gli esami radiologici non abbiano individuato alcuna complicanza. La radiologia è fondamentale nella valutazione dei pazienti sot - toposti a questo tipo di intervento e nella individuazione delle possi - bili complicanze

Preoperative locoregional staging of rectal carcinoma: comparison of MR, TRUS and Multislice CT. Personal experience.

The aim of this study was to measure the sensitivity and clinical indications of Magnetic Resonance (MR) as compared to Transrectal Ultrasonography (TRUS) and spiral Computed Tomography (CT) in the preoperative staging and evaluation of rectal carcinoma. Twenty patients with histologically proven rectal carcinoma were examined with phased-array coil MRI. We used T1 and T2, spin-echo, turbo-spin-echo, flash2D sequences with and without fat suppression; FOV 180-280; 4-6 mm slice thickness; i.v. Gadolinium. The MR images were compared with TRUS, spiral CT and with the final histological diagnosis. MR showed a 92.3% sensitivity for rectal wall infiltration vs. 100% of TRUS and 75% of CT. The sensitivity for lymph node metastases was 76.4% vs. 72.2% for TRUS and 88% for CT. Locoregional staging of rectal cancer by MRI shows a high sensitivity and is also feasible in stenosing or proximal rectal lesions. TRUS, despite its limitations, is still the most sensitive method for the evaluation of wall infiltration. CT was less sensitive than the other two The sensitivity of MR and CT for lymph node metastases is comparable, but the former is more specific

Effects of natural compounds on the oxidative balance in pediatric acute lymphoblastic leukemia.

Most of the recently developed anticancer drugs induce apoptotic cell death in tumor cells through up-regulating the intracellular ROS levels. New evidence suggests the promising role of curcumin, a yellow-gold color phytochemical turmeric, isolated from root of the Curcuma longa, and of graviola, (Annona muricata), a tropical plant belonging to family Annonaceae, known for its medicinal uses, in the treatment of cancer1-2. In our study we analyzed the effects on proliferation and apoptosis in ALL and Jurkat cell line of graviola and curcumin, alone and in combination with various chemotherapeutic agents (Daunorubicin, L-Asparaginase, Metotrexate, Vincristine and Desametazone). The proliferation, apoptosis, cell cycle and ROS production, before and after treatment with a ROS inhibitor, were investigated. Cell fragmentation was observed in Time lapse Imaging. Results: Our preliminary data showed an inhibition of proliferation and an apoptosis induction after 20µg/mL both of curcumin and graviola treatment for 24h. The combined treatment of curcumin respectively with Daunorubicin, L-ASPA, Vincristine and Desametazone showed a significant shift from early to late apoptosis after 24h, using the lowest effective concentration of drugs, compared to the higher dose of drugs alone: the average apoptotic increase was 49 ± 6.3% (p<0.05). Confocal analysis confirmed the internalization of curcumin in Jurkat cells, leading to cytoplasmic and partly nuclear fragmentation, especially when combined with vincristine. Curcumin treatment increased intracellular ROS levels, thus inducing apoptosis in leukemia cells. This selective activity could be attributed to the different redox states between healthy cells and leukemic cells. Curcumin has been described as an inducer of apoptosis and cell cycle arrest via regulating multiple cancer signaling pathways. The molecular insight onto curcumin-mediated anticancer property in leukemia suppression remains to be elucidated. 1.Larasati YA et al. Sci Rep 2018, 8(1):2039 2.Deep G et al. Sci Rep 2016,6:2313

Role of rMnSOD as cytotoxic agent and chemotherapy enhancer in paediatric acute lymphoblastic leukemia B cells.

The promising results about the oncotoxic action of a new molecule ( rMnSOD) on cultured acute lymphoblastic leukemia B cells from pediatric patients are describe