Effect of long-acting injectable antipsychotics on hospitalizations and global functioning in schizophrenia: a naturalistic mirror-image study

BACKGROUND: Partial adherence to antipsychotics is the most common cause of relapses and rehospitalization in patients with schizophrenia (SZ), leading to higher health care costs and psychosocial disability. The use of long-acting injectable (LAI) antipsychotics may improve therapeutic continuity and adherence to treatment. OBJECTIVE: To assess the effectiveness of switching from oral antipsychotics (OAs) to long-acting antipsychotics. METHODS: This 1-year mirror-image study evaluated the effect of switching from OAs to LAIs on the reduction of psychiatric hospitalizations and the improvement of global functioning in patients with schizophrenia. Differences in outcomes between second-generation (SGA) LAIs and first-generation (FGA) LAIs were also analyzed. RESULTS: In all, 166 patients were included: 32.5% treated by FGA-LAIs and 67.5% by SGA-LAIs. There was an overall reduction of 71% in the average number of hospital admissions and an overall improvement of 29.3% in the Global Assessment of Functioning (GAF) score between the previous 12 months and the 12 months following the switching to LAIs. Patients who switched to SGA-LAIs had no significant differences in hospitalization occurrences but a significant improvement in GAF scores when compared with patients who switched to FGA-LAIs. CONCLUSION: Our results suggest that using LAIs could be the most adequate treatment choice for SZ patients with a high risk of relapse and low adherence rate. Patients with poorer social functioning may be ideal candidates for SGA-LAIs treatment. Our findings may be of particular interest from a clinical and health care management perspective

Involvement of the Soluble Urokinase Receptor in Chondrosarcoma Cell Mobilization

High levels of urokinase receptor (uPAR) in tissue and serum of patients with chondrosarcoma correlate with poor prognosis. First, we analyzed the uPAR levels in tissues and plasma of five patients affected by chondrosarcoma. Interestingly, very high levels of uPAR and its soluble forms (SuPAR) were found on tumor cell surfaces and plasma, respectively, of two patients with lung metastases. Therefore, to investigate the role of SuPAR in chondrosaromas, we generated a primary cell culture from a chondrosarcoma tissue overexpressing uPAR on cell surfaces. We found that chondrosarcoma-like primary culture cells release a large amount of SuPAR in the medium. In vitro, SuPAR elicits chondrosarcoma cell migration likely through its uPAR88-92 sequence, since the DII88-183 or DIIDIIR88-284 uPAR domains retain motogen effect whereas DI1-87 or DIII184-284 domains, both lacking the uPAR88-92 sequence, are ineffective. Chondrosarcoma cells cross matrigel in response to SuPAR, and their invasion capability is abrogated by RERF peptide which inhibits uPAR88-92 signalling. These findings assign a role to uPAR in mobilizing chondrosarcoma cells and suggest that RERF peptide may be regarded as a prototype to generate new therapeutics for the chondrosarcoma treatment

Gluten deprivation: What nutritional changes are found during the first year in newly diagnosed coeliac children?

Aim: A gluten-free diet (GFD) can expose children to excessive calories and fat intake. The study is intended to verify whether and how food intake, laboratory parameters, and growth are modified by a year of GFD. Methods: In 79 CD (coeliac disease) children (mean age 7.9 \ub1 3.8 years, 52 females, 27 males) diagnosed over 24 months, 24-h food diaries, food-frequency patterns, anthropometric and laboratory parameters (mainly blood sugar, insulin, lipid profile, and homocysteine) were prospectively collected before and during the first year of GFD. Nutrient intakes were compared over time and with recommendations. They were also used as regressors to explain the levels and changes of metabolic and growth variables. p-values < 0.05 were considered statistically significant. Results: Average macronutrient intake did not change during the year. Caloric intake remained below 90% (p 64 0.0001) and protein intake above 200% (p 64 0.0001) of recommendations. Lipid intake was stable at 34% of overall energy intake. Unsaturated fats increased (less omega-6 and more omega-3 with a ratio improvement from 13.3 \ub1 5.5 to 8.8 \ub1 3.1) and so did fibers, while folate decreased. The children who experienced a containment in their caloric intake during the year, presented a slower catch-up growth. Some differences were found across gender and age groups. In particular, adolescents consumed less calories, and females more omega-3. Fiber and simple sugar intakes emerged as implicated in lipid profile shift: fibers negatively with triglycerides (TG) (p = 0.033), simple sugars negatively with high-density lipoprotein (HDL) (p = 0.056) and positively with TG (p = 0.004). Waist-to-height ratio was positively associated with homocysteine (p = 0.018) and Homeostasis Model Assessment (p = 0.001), negatively with fibers (p = 0.004). Conclusion: In the short run, GFD is nutritionally very similar to any diet with gluten, with some improvements in unsaturated fats and fiber intake. Along with simple sugars containment, this may offer CD patients the opportunity for a fresh start. Caloric intakes may shift and should be monitored, especially in adolescents

Impact of pe_pgrs33 gene polymorphisms on mycobacterium tuberculosis infection and pathogenesis

PE_PGRS33 is a surface-exposed protein of Mycobacterium tuberculosis (Mtb) which exerts its role in macrophages entry and immunomodulation. In this study, we aimed to investigate the polymorphisms in the pe_pgrs33 gene of Mtb clinical isolates and evaluate their impact on protein functions. We sequenced pe_pgrs33 in a collection of 135 clinical strains, genotyped by 15-loci MIRU-VNTR and spoligotyping and belonging to the Mtb complex (MTBC). Overall, an association between pe_pgrs33 alleles and MTBC genotypes was observed and a dN/dS ratio of 0.64 was obtained, suggesting that a purifying selective pressure is acting on pe_pgrs33 against deleterious SNPs. Among a total of 19 pe_pgrs33 alleles identified in this study, 5 were cloned and used to complement the pe_pgrs33 knock-out mutant strain of Mtb H37Rv (Mtb\uce\u9433) to assess the functional impact of the respective polymorphisms in in vitro infections of primary macrophages. In human monocyte-derived macrophages (MDMs) infection, large in-frame and frameshift mutations were unable to restore the phenotype of Mtb H37Rv, impairing the cell entry capacity of Mtb, but neither its intracellular replication rate nor its immunomodulatory properties. In vivo studies performed in the murine model of tuberculosis (TB) demonstrated that the Mtb\uce\u9433 mutant strain was not impaired in the ability to infect and replicate in the lung tissue compared to the parental strain. Interestingly, Mtb\uce\u9433 showed an enhanced virulence during the chronic steps of infection compared to Mtb H37Rv. Similarly, the complementation of Mtb\uce\u9433 with a frameshift allele also resulted in a Mtb strain capable of causing a surprisingly enhanced tissue damage in murine lungs, during the chronic steps of infection. Together, these results further support the role of PE_PGRS33 in the pathogenesis and virulence of Mtb

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

How future surgery will benefit from SARS-COV-2-related measures: a SPIGC survey conveying the perspective of Italian surgeons

COVID-19 negatively affected surgical activity, but the potential benefits resulting from adopted measures remain unclear. The aim of this study was to evaluate the change in surgical activity and potential benefit from COVID-19 measures in perspective of Italian surgeons on behalf of SPIGC. A nationwide online survey on surgical practice before, during, and after COVID-19 pandemic was conducted in March-April 2022 (NCT:05323851). Effects of COVID-19 hospital-related measures on surgical patients' management and personal professional development across surgical specialties were explored. Data on demographics, pre-operative/peri-operative/post-operative management, and professional development were collected. Outcomes were matched with the corresponding volume. Four hundred and seventy-three respondents were included in final analysis across 14 surgical specialties. Since SARS-CoV-2 pandemic, application of telematic consultations (4.1% vs. 21.6%; p &lt; 0.0001) and diagnostic evaluations (16.4% vs. 42.2%; p &lt; 0.0001) increased. Elective surgical activities significantly reduced and surgeons opted more frequently for conservative management with a possible indication for elective (26.3% vs. 35.7%; p &lt; 0.0001) or urgent (20.4% vs. 38.5%; p &lt; 0.0001) surgery. All new COVID-related measures are perceived to be maintained in the future. Surgeons' personal education online increased from 12.6% (pre-COVID) to 86.6% (post-COVID; p &lt; 0.0001). Online educational activities are considered a beneficial effect from COVID pandemic (56.4%). COVID-19 had a great impact on surgical specialties, with significant reduction of operation volume. However, some forced changes turned out to be benefits. Isolation measures pushed the use of telemedicine and telemetric devices for outpatient practice and favored communication for educational purposes and surgeon-patient/family communication. From the Italian surgeons' perspective, COVID-related measures will continue to influence future surgical clinical practice

Ant Colony Optimization for Tree-Searching based Synthesis of Monopulse Array Antenna

The design of simple feed networks is of great interest in synthesizing monopulse radar array antennas in order to reduce the complexity of the antenna architecture, the costs as well as the occupied physical space (e.g., on aircrafts). Sub-arraying techniques have been proposed to properly address such a task. In this letter, starting from the formulation of the sub-arraying problem in terms of a combinatorial one, the final compromise solution is obtained by looking for the minimum cost path inside a binary tree graph through an Ant Colony Optimizer. This paper is a postprint of a paper submitted to and accepted for publication in Electronics Letters and is subject to Institution of Engineering and Technology Copyright. The copy of record is available at IET Digital Library

A Full Scale Test Rig to Characterize Pneumatic Tyre Mechanical Behaviour

In this paper an experimental test rig aimed to characterize mechanical properties of a pneumatic tyre, together with some results, is presented. The objective is to determine tyre mechanical characteristics useful to physically model its behaviour; in particular: the normal interaction characteristic, the radial stiffness, the total stiffness and the longitudinal hysteretic cycles. To this aim two different kind of tests have been executed: radial and longitudinal. In the radial test the load is statically applied to the tyre, along the vertical direction, by means of an hydraulic press and it is measured together with the consequent radial deformation, so allowing the estimation of the tyre normal interaction characteristic and of its radial stiffness. Different radial tests can be conducted for an assigned tyre varying the inflation pressure. The longitudinal tests are conducted applying, under an assigned constant vertical load, a variable horizontal strain to the tyre by means of a linear actuator, two profile rail guides and a system to transfer the horizontal motion to the contact patch of the tyre, opportunely placed on a moving steel plate placed on the two linear guide rails. During the tests the horizontal load and the resulting deformations are measured and acquired so allowing the estimation of tyre total stiffness and of its longitudinal hysteretic cycles. Longitudinal tests can be conducted varying the assigned vertical load, the horizontal displacement law in terms of frequency and amplitude, the tyre inflation pressure. All the different types of rim can be mounted on the test rig thanks to a universal quick flange

Analysis of gear rattle by means of a wavelet-based signal processing procedure

In the paper a wavelet-based signals processing technique for the experimental detection of the gear rattle produced by the teeth impacts in lightly loaded gears is proposed. The Discrete Wavelet Transform is used to decompose the signal of the angular relative motion of an helical gear pair, and the wavelet decomposition details are adopted to analyze the dynamic behavior under rattle condition. In particular the procedure permits to evaluate the quality of the impacts between the teeth, discriminating between the two different sides of teeth contacts when there is a double-sided rattle condition. This technique enables, moreover, to define new indices for metrics of gear rattle especially useful in order to conduct comparisons for different operative conditions. Some examples of application of the proposed technique are reported in the paper adopting experimental signals acquired by two high resolution incremental encoders on a specific gear pair test rig. The experimental investigations regard comparative analyses with respect to the speed fluctuations amplitude, the rattle frequency and the lubricatio