Up to date, tissue regeneration of large bone defects is a clinical challenge under exhaustive study. Nowadays, the most common clinical solutions concerning bone regeneration involve systems based ...on human or bovine tissues, which suffer from drawbacks like antigenicity, complex processing, low osteoinductivity, rapid resorption and minimal acceleration of tissue regeneration. This work thus addresses the development of nanofibrous synthetic scaffolds of polycaprolactone (PCL) - a long-term degradation polyester - compounded with hydroxyapatite (HA) and variable concentrations of ZnO as alternative solutions for accelerated bone tissue regeneration in applications requiring mid- and long-term resorption. In vitro cell response of human fetal osteoblasts as well as antibacterial activity against Staphylococcus aureus of PCL:HA:ZnO and PCL:ZnO scaffolds were here evaluated. Furthermore, the effect of ZnO nanostructures at different concentrations on in vitro degradation of PCL electrospun scaffolds was analyzed. The results proved that higher concentrations ZnO may induce early mineralization, as indicated by high alkaline phosphatase activity levels, cell proliferation assays and positive Alizarin-Red-S-stained calcium deposits. Moreover, all PCL:ZnO scaffolds particularly showed antibacterial activity against S. aureus which may be attributed to release of Zn2+ ions. Additionally, results here obtained showed a variable PCL degradation rate as a function of ZnO concentration. Therefore, this work suggests that our PCL:ZnO scaffolds may be promising and competitive short-, mid- and long-term resorption systems against current clinical solutions for bone tissue regeneration.
•We synthesized electrospun PCL scaffolds compounded with ZnO nanostructures and hydroxyapatite•We evaluated in vitro the effect of the content of ZnO nanostructures on osteoblasts and S. aureus.•We evaluated the in vitro degradation of our scaffolds in function of ZnO content•We demonstrated in vitro mineralization of our scaffolds as well as a significant antibacterial efficacy against S. aureus•We proved the acceleration and regulation of the degradation rate of our scaffolds by compounding with ZnO nanostructures.
Aim
To examine the incidence of with first‐episode psychosis (FEP) in the Integrated Department of Mental Health and Pathological Addictions in Ferrara, Italy, and to examine the association between ...the Duration of Untreated Psychosis (DUP) and the clinical course.
Methods
Participants recruited in 2013–2019 were assessed with the Health of the Nation Outcome Scale (HoNOS) every 6 months for 24 months. Hierarchical growth models analysed changes of global severity (HoNOS total scores) and symptom dimensions. Regression modelled factors associated with remission (HoNOS < 8) and clinical improvement (<12).
Results
The incidence of FEP was 21.5 (95%CI: 21.2–21.9) cases per 100 000 person year. Among participants (n = 86, mean age 23, 76% males), baseline HoNOS scores were higher for those with a longer DUP. More than half subjects reached clinical remission (61.6%) or improvement (82.6%), while very few (2.3%) were re‐hospitalized. HoNOS total scores decayed with a mixed linear/quadratic trend, with a slower decay among migrants. A longer DUP was associated with reduced improvements of positive symptoms and lower likelihood of clinical improvement (OR: 0.84; 95%CI: 0.73–0.96).
Conclusions
Patients from the FEP program of Ferrara reached good clinical outcomes. Nonetheless, individuals with a longer DUP may need additional clinical attention. Systematic monitoring of clinical outcomes may be an optimal strategy to improve the outcomes of FEP in the real world.
Lecithin:cholesterol acyltransferase (LCAT) is the enzyme responsible for cholesterol esterification in plasma. Mutations in the LCAT gene leads to two rare disorders, familial LCAT deficiency and ...fish-eye disease, both characterized by severe hypoalphalipoproteinemia associated with several lipoprotein abnormalities. No specific treatment is presently available for genetic LCAT deficiency. In the present study, recombinant human LCAT was expressed and tested for its ability to correct the lipoprotein profile in LCAT deficient plasma. The results show that rhLCAT efficiently reduces the amount of unesterified cholesterol (−30%) and promotes the production of plasma cholesteryl esters (+210%) in LCAT deficient plasma. rhLCAT induces a marked increase in HDL-C levels (+89%) and induces the maturation of small preβ-HDL into alpha-migrating particles. Moreover, the abnormal phospholipid-rich particles migrating in the LDL region were converted in normally sized LDL.
•Human rLCAT was produced in HEK cells and proved to be active.•rhLCAT promotes the formation of cholesteryl esters in FLD plasma.•rhLCAT induces the maturation of discoidal preβ-HDL in FLD plasma.•rhLCAT normalizes the VLDL/LDL profile in FLD plasma.
Background: Major depressive disorder (MDD) is prevalent and disabling among older adults. Standing on its tolerability profile, vortioxetine might be a promising alternative to selective serotonin ...reuptake inhibitors (SSRIs) in such a vulnerable population. Methods: We conducted a randomised, assessor- and statistician-blinded, superiority trial including older adults with MDD. The study was conducted between 02/02/2019 and 02/22/2023 in 11 Italian Psychiatric Services. Participants were randomised to vortioxetine or one of the SSRIs, selected according to common practice. Treatment discontinuation due to adverse events after six months was the primary outcome, for which we aimed to detect a 12% difference in favour of vortioxetine. The study was registered in the online repository clinicaltrials.gov (NCT03779789). Findings: The intention-to-treat population included 179 individuals randomised to vortioxetine and 178 to SSRIs. Mean age was 73.7 years (standard deviation 6.1), and 264 participants (69%) were female. Of those on vortioxetine, 78 (44%) discontinued the treatment due to adverse events at six months, compared to 59 (33%) of those on SSRIs (odds ratio 1.56; 95% confidence interval 1.01–2.39). Adjusted and per-protocol analyses confirmed point estimates in favour of SSRIs, but without a significant difference. With the exception of the unadjusted survival analysis showing SSRIs to outperform vortioxetine, secondary outcomes provided results consistent with a lack of substantial safety and tolerability differences between the two arms. Overall, no significant differences emerged in terms of response rates, depressive symptoms and quality of life, while SSRIs outperformed vortioxetine in terms of cognitive performance. Interpretation: As opposed to what was previously hypothesised, vortioxetine did not show a better tolerability profile compared to SSRIs in older adults with MDD in this study. Additionally, hypothetical advantages of vortioxetine on depression-related cognitive symptoms might be questioned. The study's statistical power and highly pragmatic design allow for generalisability to real-world practice. Funding: The study was funded by the Italian Medicines Agency within the “2016 Call for Independent Drug Research”.
HIV protease inhibitors have been shown to exert antiangiogenic and antitumor actions independently from their antiretroviral effect. Based on these studies, HIV-seronegative patients with classic ...Kaposi's sarcoma were treated with indinavir and followed for clinical evolution, drug pharmacokinetics and Kaposi's sarcoma biomarkers. A favorable clinical course was associated with high drug plasma levels, reduced production of basic fibroblast growth factor, lower numbers of circulating endothelial cells, and a decrease in antibody titers against human herpesvirus 8.
To identify the phenotypic variations in 6 related individuals affected by a novel mutation in the retinal degeneration slow/peripherin gene.
Ten family members underwent ophthalmologic assessment ...with slit-lamp biomicroscopy, dilated fundus examination, fundus photography, autofluorescence imaging and electrophysiological tests. Genomic DNA was extracted from blood samples of all family members (n = 15) using the standard salting-out procedure.
The novel C165R mutation was identified in 8 individuals. Of these 8 patients, only 6 gave consent to the clinical study. They had a retinal disease characterized by an adulthood onset of symptoms, and their best corrected visual acuity was between 20/50 and 20/20. Fundus examination showed that 3 patients had typical fundus flavimaculatus: 1 had butterfly-shaped pattern dystrophy and 2 had incipient retinal changes.
We identified a novel mutation of the retinal degeneration slow/peripherin gene in a family affected by different patterns of retinal dystrophy. This is the first report of an association of fundus flavimaculatus with butterfly-shaped pattern dystrophy.
Introducción: previamente se ha demostrado que los pacientes diabéticos poseen una incidencia aumentada de patologías micro y macrovasculares. En la exploración de posibles determinantes aparece como ...candidato atractivo el gen de la enzima convertidora de angiotensina (ECA) el cual presenta de acuerdo al polimorfismo InDel existente, un aumento de la concentración enzimática en sangre asociado a enfermedades vasculares. Objetivo: se plantearon como objetivos establecer la prevalencia del polimorfismo del gen de la ECA, en pacientes diabéticos y comparar las frecuencias con las halladas para la población general de manera de revelar si existe asociación del locus con la diabetes mellitus. Material y método: la población estudiada consistió en 131 individuos con diagnóstico certero de diabetes según criterios de la American Diabetes Association. Se hallaron las frecuencias génicas y genotípicas del polimorfismo InDel del gen de la ECA mediante la técnica de reacción en cadena de la polimerasa (PCR). Resultados: no se encontraron diferencias significativas en la prevalencia del marcador estudiado entre diabéticos y la población general. Las frecuencias génicas halladas en diabéticos fueron 0,435 para alelo I y 0,565 para alelo D versus 0,440 alelo I y 0,560 alelo D en la población general. Discusión: en suma, este marcador es un factor de riesgo que no está asociado a la diabetes en sí misma, sino que la relación entre este gen y las complicaciones vasculares serían las mismas para diabéticos que para la población general.
BACKGROUNDIota-Carrageenan (I-C) is a sulfate polysaccharide synthesized by red algae, with demonstrated antiviral activity and clinical efficacy as nasal spray in the treatment of common cold. In ...vitro, I-C inhibits SARS-CoV-2 infection in cell culture.RESEARCH QUESTIONCan a nasal spray with Iota-Carrageenan be useful in the prophylaxis of COVID-19 in health care workers managing patients with COVID-19 disease?STUDY DESIGN AND METHODSThis is a pilot pragmatic multicenter, randomized, double-blind, placebo-controlled study assessing the use of a nasal spray containing I-C in the prophylaxis of COVID-19 in hospital personnel dedicated to care of COVID-19 patients. Clinically healthy physicians, nurses, kinesiologists and other health care providers managing patients hospitalized for COVID-19 were assigned in a 1:1 ratio to receive four daily doses of I-C spray or placebo for 21 days. The primary end point was clinical COVID-19, as confirmed by reverse transcriptase polymerase chain reaction testing, over a period of 21 days. The trial is registered at ClinicalTrials.gov (NCT04521322).RESULTSA total of 394 individuals were randomly assigned to receive I-C or placebo. Both treatment groups had similar baseline characteristics. The incidence of COVID-19 differs significantly between subjects receiving the nasal spray with I-C (2 of 196 1.0%) and those receiving placebo (10 of 198 5.0%). Relative risk reduction: 79.8% (95% CI 5.3 to 95.4; p=0.03). Absolute risk reduction: 4% (95% CI 0.6 to 7.4).INTERPRETATIONIn this pilot study a nasal spray with I-C showed significant efficacy in preventing COVID-19 in health care workers managing patients with COVID-19 disease.CLINICAL TRIALS REGISTRATIONNCT04521322.
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