Introduction
Three generations of antipsychotics, all of which are based on the dopaminergic hypothesis of schizophrenia, are available for clinical use. Still, more than 66% of the patients ...diagnosed with schizophrenia spectrum disorders (SSD) could not achieve remission. Also, the glutamatergic hypothesis of schizophrenia is supported by translational models of this disease, even if the antipsychotics derived from this conceptual framework are not yet available on the market. However, the need for new pathogenesis models for schizophrenia and new generations of antipsychotics is acute, therefore, an exploration of the antipsychotics in the pipeline could be helpful in understanding the current stage of research in schizophrenia.
Objectives
To assess the evidence supporting the potential benefits of new antipsychotics in the pipeline.
Methods
A literature review was performed through the main electronic databases PubMed, Cochrane, Clarivate/Web Of Science, and EMBASE) and clinical trials repositories (US National Library of Medicine and World Health Organization Clinical Trials Registry Platform) using the search paradigm “antipsychotics” AND “schizophrenia” AND “non-dopaminergic” AND “non-glutamatergic”. All papers published between January 2010 and September 2022 were included.
Results
Xanomeline/trospium (xanomeline is a muscarinic M1/M4 receptor agonist at the central nervous system, while trospium limits its peripheral effects) was efficient for schizophrenia in one phase III clinical trial. Pimavanserin (a selective 5HT2A inverse agonist and antagonist) was efficient in improving negative symptoms of schizophrenia in a phase II trial. Roluperidone (a 5HT2A and σ2 receptor antagonist) has been associated with favorable results in phase III clinical trials, mainly on negative symptoms of schizophrenia. SEP-363856 is a TAAR-1 agonist and 5HT1A agonist, currently explored in phase III clinical trials for schizophrenia. MK-8189 is a phosphodiesterase 10A inhibitor, investigated in phase III clinical trials for schizophrenia.
Conclusions
Based on the retrieved data in the literature, multiple mechanisms, other than glutamatergic and dopaminergic pathways, are currently being investigated, and many of the antipsychotics based on these mechanisms are in the advanced stage of research. This is important not only for the clinical need to find more efficient and tolerable drugs for patients with schizophrenia but also because they may shed new light on the pathogenesis of this disease.
Disclosure of Interest
None Declared
Introduction: Diverse musculo-skeletal pathology can be treated conservatively by different types of injections and in most cases, results are significantly better if the existing inflammatory fluid ...is aspirated prior to injection of medication solutions. The present study analyses an original technique which uses infusion therapy accessories to create two types of closed sterile double syringe systems, and compares the benefits of using such a system in aspiration/injection procedures to classic aspiration injection technique that implies changing and connecting multiple syringes to the same needle, thus increasing the risk for septic complications. The aim of the present study is to minimize therapeutic risk of iatrogenic septic complications during aspiration/injection procedures. Methods: 1024 patients underwent aspiration/injection procedures in our clinic using the double syringe system between 2015 and 2020. During the early stages of the study, the second type of assembly was rendered impractical so the study continued with analyzing a single type of double syringe system using a three way infusion therapy device which is readily available, and allows the assembly of a closed sterile system with a single, two-step procedure technique. Iatrogenic local septic complications were followed by means of a six week clinical follow-up evaluation with additional investigations only if necessary. Results: In 1024 procedures we report 0% incidence of iatrogenic septic complications, or other types of complications and recommend this technique in a vast array of rheumatic, orthopedic or traumatic conditions that require aspiration/injection procedures. Discussion: The double syringe system is practical, easy to use, it completely eliminates the risk of iatrogenic infection due to manipulation errors, and significantly simplifies the technique for sonography guided aspiration/injection procedures for musculo- skeletal pathology. Keywords: musculo-skeletal injections, aspiration/injection technique, double syringe system, iatrogenic infection, rheumatology, joint pathology
Arterial stiffness estimated by pulse wave velocity (PWV) is an independent predictor of cardiovascular morbidity and mortality. Although recommended by the current guidelines, clinical applicability ...of this parameter is difficult, due to differences between the various techniques used to measure it and to biological variability. Our aim was to compare PWV assessed by 3 different commercially available systems. 100 subjects (51 ± 16 years, 45 men) were evaluated using the 3 methods: an oscillometric technique (Arteriograph, PWV-A); a piezo-electric method (Complior, PWV-C); and an high-resolution ultrasound technique implemented with an Echo-tracking system (Aloka, PWV-E). Conventional biological markers were measured. Correlations of PWV measured by the 3 methods were poor (
r
= 0.39,
r
= 0.39, and
r
= 0.31 for PWV-A vs. PWV-C, PWV-A vs. PWV-E, and PWV-C vs. PWV-E, respectively, all
p
< 0.05). By Bland–Altman analysis, mean difference (±SD) of PWV-A vs. PWV-C was −1.9 ± 2.0 m/s, of PWV-A vs. PWV-E −3.6 ± 1.9 m/s, and of PWV-C vs. PWV-E −2.7 ± 1.9 m/s, with a wide coefficient of variation (22.3, 25.7, and 25.7 %, respectively). As expected, PWV-A, PWV-C, and PWV-E correlated with other arterial stiffness parameters, such as intima-media thickness (
r
= 0.22,
r
= 0.22, and
r
= 0.36, respectively),
E
p
(
r
= 0.37,
r
= 0.26, and
r
= 0.94, respectively), and augmentation index measured by Arteriograph method (
r
= 0.66,
r
= 0.35, and
r
= 0.26, respectively); all
p
< 0.05. Assessment of PWV is markedly dependent on the technique used to measure it, related to various methods for measuring traveled distance of the arterial wave. Our results suggest the urgent need to establish reference values of PWV for each of these techniques, separately, to be used in routine clinical practice.
Abstract
The scope of this review article is to offer a general view of the recent advances in the plasma electrolytic oxidation of Mg and Mg alloys with emphasis of the Plasma Electrolytic Oxidation ...(PEO) processing parameters used to obtain key surface properties for medical and engineering applications. The paper presents the different dependencies of the PEO process, first of all depending on the composition of the substrate, the electrolyte used, the applied electrical regime, as well as the way of their interaction, with direct implications on the properties designed to satisfy concrete applications for magnesium alloys. Magnesium-deformable alloys are of particular interest for the manufacture of parts for the for medical and engineering applications and industry due to the possibility of obtaining a more homogeneous structure and better mechanical properties, compared to cast parts. Also, magnesium alloys find its place to a broad range of aerospace, electronics, commercial and sport-related applications. In general, the interactions of the substrate / electrolyte combination with the electrical regime are complex and still the subject of ample research. Because, unlike other electrolytic surface treatment methods, PEO results in the formation of high-strength ohmic layers, they affect, especially in the case of current-controlled regimes, the extent to which the predefined electrical pulse is projected correctly in the setting experimental data.
We designed novel 4′-modified 2′-deoxy-2′-fluorouridine (2′-F U) analogues with the aim to improve nuclease resistance and potency of therapeutic siRNAs by introducing 4′-C-methoxy (4′-OMe) as the ...alpha (C4′α) or beta (C4′β) epimers. The C4′α epimer was synthesized by a stereoselective route in six steps; however, both α and β epimers could be obtained by a nonstereoselective approach starting from 2′-F U. 1H NMR analysis and computational investigation of the α-epimer revealed that the 4′-OMe imparts a conformational bias toward the North-East sugar pucker, due to intramolecular hydrogen bonding and hyperconjugation effects. The α-epimer generally conceded similar thermal stability as unmodified nucleotides, whereas the β-epimer led to significant destabilization. Both 4′-OMe epimers conferred increased nuclease resistance, which can be explained by the close proximity between 4′-OMe substituent and the vicinal 5′- and 3′-phosphate group, as seen in the X-ray crystal structure of modified RNA. siRNAs containing several C4′α-epimer monomers in the sense or antisense strands triggered RNAi-mediated gene silencing with efficiencies comparable to that of 2′-F U.
HIV/HCV prevention among people who inject drugs (PWID) is of key public health importance. We aimed to assess the impact of COVID-19 and associated response measures on HIV/HCV prevention services ...and socio-economic status of PWID in high-HIV-risk sites. Sites with recent (2011–2019) HIV outbreaks among PWID in Europe North America and Israel, that had been previously identified, were contacted early May 2020. Out of 17 sites invited to participate, 13 accepted. Semi-structured qualitative site reports were prepared covering data from March to May 2020, analyzed/coded and confirmed with a structured questionnaire, in which all sites explicitly responded to all 103 issues reported in the qualitative reports. Opioid maintenance treatment, needle/syringe programs and antiretroviral treatment /hepatitis C treatment continued, but with important reductions and operational changes. Increases in overdoses, widespread difficulties with food and hygiene needs, disruptions in drug supply, and increased homelessness were reported. Service programs rapidly reformed long established, and politically entrenched, restrictive service delivery policies. Future epidemic control measures should include mitigation of negative side-effects on service provision and socio-economic determinants in PWID.
This paper presents a simple and effective bottom-up approach to design novel biohybrids based on biomimetic membranes and carbon nanotubes. Multilamellar and unilamellar lipid vesicles loaded with ...two antioxidants (quercetin and chlorophyll a) were obtained by thin film hydration method and have been used to prepare two types of biohybrid systems by addition of carbon nanotubes to these liposome suspensions. Chlorophyll a inserted into biomimetic membranes was used as a spectral marker to detect the changes occurred in the artificial lipid bilayers. The obtained carbon-based biohybrids exhibited antioxidant and antimicrobial properties and also a good physical stability.
Hysterectomy is one of the most important surgeries in gynecology and requires a lot of care and skill. In this study we attempt to make a comparison between laparoscopic hysterectomy, robotic ...assisted hysterectomy and abdominal hysterectomy for treatment of uterine pathology.
We conducted a study comparing 29 patients who were treated by robotic assisted laparoscopic hysterectomy in Cisanello Hospital, Pisa, Italy, 30 patients who were treated by laparoscopy in General Surgery Clinic, Craiova and 30 patients who were treated by abdominal hysterectomy in General Surgery Clinic, Craiova.
Comparing the surgeries, it was noticed that the operative time of a robotic assisted interventions is the largest, 183.9 minutes. Even if the duration was greater, the time needed to perform vaginal suture was lower, 17.75 minutes to 22.79 minutes by classic laparoscopic approach. In terms of blood loss we concluded that intraoperative blood loss was lowest during a robotic surgery, 199.3 ml versus 285 ml in the laparoscopic group and 417 ml in the laparotomic group.
Robotic assisted laparoscopic hysterectomy is a feasible method that can be used very successfully to treat patients diagnosed with benign uterine pathology.
This study investigates new developments of thermal catalytic pyrolysis using transition metals (Fe2+, Fe3+) supported on ZSM-5 zeolites applied to a feedstock originated from the food court areas ...which can be considered representative for Municipal Solid Waste(MSW).The catalytic pyrolysis runs were performed using a two-stage process configuration: thermal pyrolysis conducted at 500 °C followed by catalytic cracking of vapors. The vapor catalytic upgrading was done ex-situ by using three types of catalysts HZSM5, Fe2+HZSM5, and Fe3+HZSM5 at 300, 350, and 400 °C. The structural features inherent of the ZSM-5 zeolites and associated properties (e.g. very regular microporosity, stability, ion exchange capacity) during pyrolytic processes, as well as the ability to accommodate chemical modification via isomorphic substitution of the tetrahedral atoms in the crystal network in presence of transition metals, make them unique catalysts scavengers. This new route can be applied to target the pyrolytic process for Food Court Waste (FCW) selective conversion and obtaining valuable intermediaries for different industries. The addition of catalysts was shown to enhance FCW decomposition at lower temperatures. The most important result observed in the pyrolysis process was obtained over Fe2+ZSM- 5 which was found to be the most efficient catalyst for waste minimization leading to high bio-oil conversion (∼40 wt% at 350 °C). The catalytic pyrolysis process of FCW provides resources for specific transformations, in target raw materials, products additives or co-formulants for biofuel manufacture or upgrading.
Display omitted
•Ex-situ catalytic pyrolysis of waste mixture into co-formulants for new performance of biodiesel.•New catalytic pyrolysis using transition metals (Fe2+, Fe3+) supported on ZSM-5.•Fe2+ZSM- 5 which was found to be the most efficient catalyst for waste minimization leading to high bio-oil conversion.•Producing levoglucosan, furfural, methylcyclopropane, 3-Methyl-1,2-cyclopentanedione.
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