Characterization of Maltese pottery of the Late Neolithic, Bronze Age and Punic Period by neutron activation analysis

A set of 41 samples from Tas-Silg, Malta, has been analysed by neutron activation. It contained nine ware groups formed by visual examination covering the Late Neolithic, Bronze Age and Punic Periods (c. 3000–218 BC). Despite this diversity and long time range, seven of these ware groups, including the ‘Thermi Ware’, all have a similar chemical composition and, therefore, have been made from the same clay. This points most probably to a local origin. One group from the Punic Period, containing only Bricky Red cooking ware, is chemically separate and represents a second distinct pattern probably assignable to a local production. Five amphora sherds also from the Punic Period, and consisting of a micaceous fabric, all have different chemical characteristics and are probably imports from overseas production sites of unknown location.peer-reviewe

Mechanically induced chondrogenesis of human bone marrow derived stem cells

Bone marrow derived mesenchymal stem cells (MSCs) have been shown to offer great promise in regenerating defects of the musculoskeletal system. Beside growth factors, mechanical load is known to regulate the phenotypic fate decision in these cells. So far, a number of studies have shown beneficial effects of load on chondrogenesis of MSCs. However, the proper mechanical input still remains unknown. This study aimed to compare the chondrogenic response of compression and shear on MSC differentiation, while varying the cell number on the upper-surface of the construct in the absence of exogenous chondrogenic stimuli. In this set of experiments, human MSCs will be seeded into fibrinpolyurethane (PU) composite scaffolds. Human bone marrow derived MSCs were seeded into three-dimensional PU scaffolds (4 x 8 mm) at a cell density of 4 x 106 per scaffold. Constructs were cultured in Dulbecco’s modified Eagle’s Medium (DMEM) with no exogenous transforming growth factor-β (TGF-β). Scaffolds were exposed to 15 loading cycles over 3 weeks, thereby assigned to 4 groups: Group A was exposed to compression and shear 4 milions MSC cells seeded into the scaffold. Group B was the free-swelling 4 milions MSC cells seeded into the scaffold (unloaded) control. Group C was exposed to compression and shear 3.6 milions MSC cells seeded into the scaffold plus 400 thousands MSC cells seeded on the top. Group D was the free-swelling 3.6 milions MSC cells seeded into the scaffold plus 400 thousands MSC cells seeded on the top (unloaded) control. Measurements included DNA, glucosaminoglycan (GAG), Elisa analysis, histology, himmunohistochemistry and mechanical competence. In addition, mRNA expression of chondrogenic markers (collagen type-II (Col 2), Aggrecan (AGG), osteogenic markers (collagen type-I (Col 1), alkaline phosphatase (ALP) and hypertrophic markers (collagen type-X (Col 10)) were assessed. Mechanical load and shear led to an increase in all the chondrogenic genes investigated with the greatest effect in group C. On mRNA level, AGG and Col 2 were upregulated to a greater extend in loaded groups compared to no loaded groups. This was reflected in the histological analysis, where only the group C showed a matrix rich in glucosaminoglycan staining. These results highlight that Group C was exposed to compression and shear 3.6 milions MSC cells seeded into the scaffold plus 400 thousands MSC cells seeded on the top demonstrated to mechanically induce in vitro chondrogenesis of MSCs. This is important knowledge for the repair of musculoskeletal disorders, whereby the same cell type (MSC) can induce bone repair as well as cartilage repair depending on the mechanical cues. Furthermore, this insight provides valuable information to optimise rehabilitation procedures to be used after implantation of MSCs for cartilage repair

M48U1 and Tenofovir combination synergistically inhibits HIV infection in activated PBMCs and human cervicovaginal histocultures

Microbicides are considered a promising strategy for preventing human immunodeficiency virus (HIV-1) transmission and disease. In this report, we first analyzed the antiviral activity of the miniCD4 M48U1 peptide formulated in hydroxyethylcellulose (HEC) hydrogel in activated peripheral blood mononuclear cells (PBMCs) infected with R5-and X4-Tropic HIV-1 strains. The results demonstrate that M48U1 prevented infection by several HIV-1 strains including laboratory strains, and HIV-1 subtype B and C strains isolated from the activated PBMCs of patients. M48U1 also inhibited infection by two HIV-1 transmitted/founder infectious molecular clones (pREJO.c/2864 and pTHRO.c/2626). In addition, M48U1 was administered in association with tenofovir, and these two antiretroviral drugs synergistically inhibited HIV-1 infection. In the next series of experiments, we tested M48U1 alone or in combination with tenofovir in HEC hydrogel with an organ-like structure mimicking human cervicovaginal tissue. We demonstrated a strong antiviral effect in absence of significant tissue toxicity. Together, these results indicate that co-Treatment with M48U1 plus tenofovir is an effective antiviral strategy that may be used as a new topical microbicide to prevent HIV-1 transmission

Wrapping and dispersion of multiwalled carbon nanotubes improves electrical conductivity of protein–nanotube composite biomaterials

Composites of extracellular matrix proteins reinforced with carbon nanotubes have the potential to be used as conductive biopolymers in a variety of biomaterial applications. In this study, the effect of functionalization and polymer wrapping on the dispersion of multiwalled carbon nanotubes (MWCNT) in aqueous media was examined. Carboxylated MWCNT were wrapped in either Pluronic ® F127 or gelatin. Raman spectroscopy and X‐ray photoelectron spectroscopy showed that covalent functionalization of the pristine nanotubes disrupted the carbon lattice and added carboxyl groups. Polymer and gelatin wrapping resulted in increased surface adsorbed oxygen and nitrogen, respectively. Wrapping also markedly increased the stability of MWCNT suspensions in water as measured by settling time and zeta potential, with Pluronic ® ‐wrapped nanotubes showing the greatest effect. Treated MWCNT were used to make 3D collagen–fibrin–MWCNT composite materials. Carboxylated MWCNT resulted in a decrease in construct impedance by an order of magnitude, and wrapping with Pluronic ® resulted in a further order of magnitude decrease. Functionalization and wrapping also were associated with maintenance of fibroblast function within protein–MWCNT materials. These data show that increased dispersion of nanotubes in protein–MWCNT composites leads to higher conductivity and improved cytocompatibility. Understanding how nanotubes interact with biological systems is important in enabling the development of new biomedical technologies. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 101A:231–238, 2013.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/94526/1/34310_ftp.pd

Water solubility enhancement of pyrazolo[3,4-d]pyrimidine derivatives via miniaturized polymer-drug microarrays

A miniaturized assay was optimized to evaluate the enhanced apparent water solubility of pyrazolo[3,4-d]pyrimidine derivatives used extensively as anticancer drug scaffolds. The applied amount of drugs used in the reported strategy ranged from 5-10 μg per formulation which were dispensed by an inkjet 2D printer directly into a 96-well plate. The selected polymer/drug formulations with high water solubility demonstrated improved cytotoxicity against a human lung adenocarcinoma cancer cell line (A549) compared to the free drugs. We attribute the enhanced efficacy to the improved apparent-solubility of the drug molecules achieved via this methodology. This novel miniaturized method showed promising results in terms of water solubility improvement of the highly hydrophobic pyrazolo[3,4-d]pyrimidine derivatives, requiring only a few μg of each drug per tested polymeric formulation. In addition, the reported experimental evidence may facilitate identification of suitable polymers for combination with drug leading to investigations on biological properties or mechanisms of action in a single formulation

Prognostic role of endocarditis in isolated tricuspid valve surgery. A propensity-weighted study

Objectives The role of the underlying etiology in isolated tricuspid valve surgery has not been investigated extensively in current literature. Aim of this study was to analyse outcomes of patients undergoing surgery due to endocarditis compared to other pathologies. Methods The SURTRI study is a multicenter study enrolling adult patients who underwent isolated tricuspid valve surgery (n = 406, 55 ± 16 y.o.; 56% female) at 13 international sites. Propensity weighted analysis was performed to compare groups (IE group n = 107 vs Not-IE group n = 299). Results No difference was found regarding the 30-day mortality (Group IE: 2.8% vs Group Not-IE = 6.8%; OR = 0.45) and major adverse events. Weighted cumulative incidence of cardiac death was significantly higher for patients with endocarditis (p = 0.01). The composite endpoint of cardiac death and reoperation at 6 years was reduced in the Group IE (63.2 ± 6.8% vs 78.9 ± 3.1%; p = 0.022). Repair strategy resulted in an increased late survival even in IE cases. Conclusions Data from SURTRI study report acceptable 30-day results but significantly reduced late survival in the setting of endocarditis of the tricuspid valve. Multi-disciplinary approach, repair strategy and earlier treatment may improve outcomes. © 2022 The Author

Neurological Disorders in Takotsubo Syndrome: Clinical Phenotypes and Outcomes

Background: Neurological disorders as a risk factor for Takotsubo syndrome (TTS) are not well characterized. The aim of the study was to evaluate TTS-associated neurological phenotypes and outcome. Methods and results: Patients with TTS enrolled in the international multicenter GEIST (German Italian Spanish Takotsubo) registry were analyzed. Prevalence, clinical characteristics, and short- and long-term outcomes of patients with TTS were recorded. A subgroup analysis of the 5 most represented neurological disorders was performed. In total, 400 (17%) of 2301 patients had neurological disorders. The most represented neurological conditions were previous cerebrovascular events (39%), followed by neurodegenerative disorders (30.7%), migraine (10%), epilepsy (9.5%), and brain tumors (5%). During hospitalization, patients with neurological disorders had longer in-hospital stay (8 [interquartile range, 5-12] versus 6 [interquartile range, 5-9] days; P<0.01) and more often experienced in-hospital complications (27% versus 16%; P=0.01) mainly driven by cardiogenic shock and in-hospital death (12% versus 7.6% and 6.5% versus 2.8%, respectively; both P<0.01). Survival analysis showed a higher mortality rate in neurological patients both at 60 days and long-term (8.8% versus 3.4% and 23.5% versus 10.1%, respectively; both P<0.01). Neurological disorder was an independent predictor of both the 60-day and long-term mortality rate (odds ratio, 1.78 [95% CI, 1.07-2.97]; P=0.02; hazard ratio, 1.72 [95% CI, 1.33-2.22]; both P<0.001). Patients with neurodegenerative disorders had the worst prognosis among the neurological disease subgroups, whereas patients with TTS with migraine had a favorable prognosis (long-term mortality rates, 29.2% and 9.7%, respectively). Conclusions: Neurological disorders identify a high-risk TTS subgroup for enhanced short- and long-term mortality rate. Careful recognition of neurological disorders and phenotype is therefore needed

Milk oligosaccharides: a review

Milk oligosaccharides (OSs) confer unique health benefits to the neonate. Although human digestive enzymes cannot degrade these sugars, they support specific commensal microbes and act as decoys to prevent the adhesion of pathogenic micro-organisms to gastrointestinal cells. The limited availability of human milk oligosaccharides (HMOs) impedes research into these molecules and their potential applications in functional food formulations. Recent studies show that complex OSs with fucose and N-acetyl neuraminic acid (key structural elements of HMO bioactivity) also exist in caprine milk, suggesting a potential source of bioactive milk OSs suitable as a functional food ingredient

Treatment of CoQ10 Deficient Fibroblasts with Ubiquinone, CoQ Analogs, and Vitamin C: Time- and Compound-Dependent Effects

Background: Coenzyme Q(10) (CoQ(10)) and its analogs are used therapeutically by virtue of their functions as electron carriers, antioxidant compounds, or both. However, published studies suggest that different ubiquinone analogs may produce divergent effects on oxidative phosphorylation and oxidative stress.Methodology/Principal Findings: To test these concepts, we have evaluated the effects of CoQ(10), coenzyme Q(2) (CoQ(2)), idebenone, and vitamin C on bioenergetics and oxidative stress in human skin fibroblasts with primary CoQ(10) deficiency. A final concentration of 5 mu M of each compound was chosen to approximate the plasma concentration of CoQ(10) of patients treated with oral ubiquinone. CoQ(10) supplementation for one week but not for 24 hours doubled ATP levels and ATP/ADP ratio in CoQ(10) deficient fibroblasts therein normalizing the bioenergetics status of the cells. Other compounds did not affect cellular bioenergetics. In COQ2 mutant fibroblasts, increased superoxide anion production and oxidative stress-induced cell death were normalized by all supplements.Conclusions/Significance: These results indicate that: 1) pharmacokinetics of CoQ(10) in reaching the mitochondrial respiratory chain is delayed; 2) short-tail ubiquinone analogs cannot replace CoQ(10) in the mitochondrial respiratory chain under conditions of CoQ(10) deficiency; and 3) oxidative stress and cell death can be counteracted by administration of lipophilic or hydrophilic antioxidants. The results of our in vitro experiments suggest that primary CoQ(10) deficiencies should be treated with CoQ(10) supplementation but not with short-tail ubiquinone analogs, such as idebenone or CoQ(2). Complementary administration of antioxidants with high bioavailability should be considered if oxidative stress is present

A vision for science education in Malta : the national curriculum framework 2011 : consultation document 2011

The current document was prepared by a working group of science and science education experts set up in November 2008 by Prof Grace Grima, Director General for Quality and Standards. The brief was to analyse the current situation of science education in Malta and to suggest a way forward that adequately addresses current as well as future national needs in the area.peer-reviewe