Effect of dietary fat level on carcass traits and flesh quality of European Sea Bass (Dicentrarchus labrax) from mariculture

The study aimed at evaluating the effect of the reduction of dietary fat on juvenile European sea bass nutritional value and quality traits. Fish were reared in floating cages (Trieste Gulf, Italy) from July (11) to October (10). Two isoproteic diets were compared: LF (low fat, EE = 19.4%) vs. HF (high fat, EE = 24.6%). No significantly different growth performance was observed. LF diet-fed fish were characterized by the reduction of celomatic fat (not edible fraction) and by the increase in dressing percentage. The tested dietary fat level also affected both fillet and epiaxial white muscle proximate composition, resulting in a significantly lower fillet lipid concentration in LF diet-fed fish. Dietary treatment influenced cooked fillet colour and texture probably as a consequence of the different intramuscular fat deposition. Fillet from HF-fed fish, in fact, presented higher lightness (L*) value and lower instrumental strengthness

Effect of unsaturated fatty acid supplementation on performance and milk fatty acid profile in dairy cows fed a high fibre diet.

The influence of unsaturated fatty acid (UFA) supplement on productive performance, physiochemical properties and fatty acid (FA) profile of milk, was investigated in lactating dairy cows fed with high fibre diets. According to a cross-over design, twelve cows were assigned to two experimental settings characterized by different FA profiles. Cows received a high fibre diet (~42% NDF on DM basis) supplemented with soybean based mixtures with these FA compositions: 92.0% of saturated FA (SFA), 2.8% of monounsaturated FA (MUFA) and 5.2% of polyunsaturated FA (PUFA) in the control diet (C-diet); 19.1% of SFA, 20.9% of MUFA and 60.0% of PUFA in the experimental diet (E-diet). The E-diet did not affect dry matter intake nor milk yield. Milk composition and coagulation traits resulted similar between treatments, except for the lactose level, which was lower in the E-diet (5.0 vs 4.8%; P<0.05) and the freezing point (-0.546 vs -0.535 °C; P<0.05). As respects the milk FA profile, the E-diet significantly increased the percentage of UFA because of their greater amount in the ration; however the "transfer" of UFA in milk was limited by the high level of FA biohydrogenation (BH) at the ruminal level. UFA showed low values of carry over in milk (67.5 vs 39.7%; P<0.001) due to the saturation process; on the contrary SFA had a threefold increment (124 vs 323%; P<0.001), mostly due to a peak in the production of stearic acid. In this study, the percentage of CLA in milk (0.50 vs 0.62%; P<0.05) was quite low for both diets, if compared with other studies, and this was probably due to a low vaccenic acid supply at duodenal level

Lecithin: a by-product of biodiesel production and a source of choline for dairy cows

The aim of the present study was to compare the effects of soy lecithins (L), a by-product of the biodiesel production process, and choline chloride microencapsulated with hydrogenated vegetable oils (C) on dry matter intake, milk yield, milk quality traits, milk choline and haematological profile of dairy cows. A total of 12 mid-lactating Holstein Friesian cows were assigned to one of two experimental groups and fed according to cross-over design (2 diets x 2 periods). Diets were isoenergetic, isofibrous and isonitrogenous and had the same content of choline. Dry matter intake was not affected by the diet, but L led to lower milk choline (P<0.05) and to a significantly higher milk yield (P<0.05), although the 3.5% fat-corrected milk (FCM) did not change owing to the higher content of fat in the milk of the C-diet group (P<0.01). The remaining milk components were unaffected by the supplements, except for the milk urea, which was lower in the L-diet group (P<0.01), reflecting a more effective use of degradable proteins by the micro-organisms present in the rumen. With regard to the haematological profile, L led to lower urea (P<0.001) and to higher values of glucose (P<0.01) and non-esterified fatty acids (NEFA)/Cholesterol ratio (P< 0.05), but all of the values fell within the physiological range of lactating dairy cows. Results indicated that soy lecithins can be used as an available and cost-effective source of choline in mid-lactating dairy cows

Rebound effects of NCX3 pharmacological inhibition: A novel strategy to accelerate myelin formation in oligodendrocytes.

Abstract The Na+/Ca2+ exchanger NCX3 is an important regulator of sodium and calcium homeostasis in oligodendrocyte lineage. To date, no information is available on the effects resulting from prolonged exposure to NCX3 blockers and subsequent drug washout in oligodendroglia. Here, we investigated, by means of biochemical, morphological and functional analyses, the pharmacological effects of the NCX3 inhibitor, the 5–amino‐N‐butyl‐2–(4–ethoxyphenoxy)-benzamide hydrochloride (BED), on NCXs expression and activity, as well as intracellular [Na+]i and [Ca2+]i levels, during treatment and following drug washout both in human MO3.13 oligodendrocytes and rat primary oligodendrocyte precursor cells (OPCs). BED exposure antagonized NCX activity, induced OPCs proliferation and [Na+]i accumulation. By contrast, 2 days of BED washout after 4 days of treatment significantly upregulated low molecular weight NCX3 proteins, reversed NCX activity, and increased intracellular [Ca2+]i. This BED-free effect was accompanied by an upregulation of NCX3 expression in oligodendrocyte processes and accelerated expression of myelin markers in rat primary oligodendrocytes. Collectively, our findings show that the pharmacological inhibition of the NCX3 exchanger with BED blocker maybe followed by a rebound increase in NCX3 expression and reversal activity that accelerate myelin sheet formation in oligodendrocytes. In addition, they indicate that a particular attention should be paid to the use of NCX inhibitors for possible rebound effects, and suggest that further studies will be necessary to investigate whether selective pharmacological modulation of NCX3 exchanger may be exploited to benefit demyelination and remyelination in demyelinating diseases

Clinical effectiveness of hymenoptera venom immunotherapy

Treatment failure during venom immunotherapy (VIT) may be associated with a variety of risk factors. Our aim was to evaluate the association of baseline serum tryptase concentration (BTC) and of other parameters with the frequency of VIT failure during the maintenance phase. In this observational prospective multicenter study, we followed 357 patients with established honey bee or vespid venom allergy after the maintenance dose of VIT had been reached. In all patients, VIT effectiveness was either verified by sting challenge (n = 154) or patient self-reporting of the outcome of a field sting (n = 203). Data were collected on BTC, age, gender, preventive use of anti-allergic drugs (oral antihistamines and/or corticosteroids) right after a field sting, venom dose, antihypertensive medication, type of venom, side effects during VIT, severity of index sting reaction preceding VIT, and duration of VIT. Relative rates were calculated with generalized additive models. 22 patients (6.2%) developed generalized symptoms during sting challenge or after a field sting. A strong association between the frequency of VIT failure and BTC could be excluded. Due to wide confidence bands, however, weaker effects (odds ratios <3) of BTC were still possible, and were also suggested by a selective analysis of patients who had a sting challenge. The most important factor associated with VIT failure was a honey bee venom allergy. Preventive use of anti-allergic drugs may be associated with a higher protection rate. It is unlikely that an elevated BTC has a strong negative effect on the rate of treatment failures. The magnitude of the latter, however, may depend on the method of effectiveness assessment. Failure rate is higher in patients suffering from bee venom allergy

Novel compound heterozygous pathogenic variants in nucleotide-binding protein like protein (NUBPL) cause leukoencephalopathy with multi-systemic involvement.

NUBPL (Nucleotide-binding protein like) protein encodes a member of the Mrp/NBP35 ATP-binding proteins family, deemed to be involved in mammalian complex I (CI) assembly process. Exome sequencing of a patient presenting with infantile-onset hepatopathy, renal tubular acidosis, developmental delay, short stature, leukoencephalopathy with minimal cerebellar involvement and multiple OXPHOS deficiencies revealed the presence of two novel pathogenic compound heterozygous variants in NUBPL (p.Phe242Leu/p.Leu104Pro). We investigated patient's and control immortalised fibroblasts and demonstrated that both the peripheral and the membrane arms of complex I are undetectable in mutant NUBPL cells, resulting in virtually absent CI holocomplex and loss of enzyme activity. In addition, complex III stability was moderately affected as well. Lentiviral-mediated expression of the wild-type NUBPL cDNA rescued both CI and CIII assembly defects, confirming the pathogenicity of the variants. In conclusion, this is the first report describing a complex multisystemic disorder due to NUBPL defect. In addition, we confirmed the role of NUBPL in Complex I assembly associated with secondary effect on Complex III stability and we demonstrated a defect of mtDNA-related translation which suggests a potential additional role of NUBPL in mtDNA expression

Analysis on in vitro effect of lithium on telomere length in lymphoblastoid cell lines from bipolar disorder patients with different clinical response to long-term lithium treatment

Background It has been suggested that bipolar disorder (BD) is associated with clinical and biological features of accelerated aging. In our previous studies, we showed that long-term lithium treatment was correlated with longer leukocyte telomere length (LTL) in BD patients. A recent study explored the role of TL in BD using patients-derived lymphoblastoid cell lines (LCLs), showing that baseline TL was shorter in BD compared to controls and that lithium in vitro increased TL but only in BD. Here, we used the same cell system (LCLs) to explore if a 7-day treatment protocol with lithium chloride (LiCl) 1 mM was able to highlight differences in TL between BD patients clinically responders (Li-R; n = 15) or non-responders (Li-NR; n = 15) to lithium, and if BD differed from non-psychiatric controls (HC; n = 15). Results There was no difference in TL between BD patients and HC. Moreover, LiCl did not influence TL in the overall sample, and there was no difference between diagnostic or clinical response groups. Likewise, LiCl did not affect TL in neural precursor cells from healthy donors. Conclusions Our findings suggest that a 7-day lithium treatment protocol and the use of LCLs might not represent a suitable approach to deepen our understanding on the role of altered telomere dynamics in BD as previously suggested by studies in vivo

Identification of protein-protein interactions of human HtrA1.

The human heat shock protein HtrA1, a member of the HtrA family of serine proteases, is a evolutionarily highly conserved factor which displays a widespread pattern of expression. The yeast two-hybrid technique was employed to identify new cellular proteins physically interacting with HtrA1, and thus potential targets of this serine protease. An enzymatically inactive HtrA1 point mutant, HtrA1-S328A, was generated and used as bait in a yeast two-hybrid system. Fifty-two plasmids were isolated from primary positive yeast clones. Subsequent sequencing and BLAST analysis revealed cDNAs encoding for 13 different proteins. These putative binding partners of HtrA1 appeared to be a) components of extracellular matrix; b) factors related to signal pathways, and c) unknown proteins. Among the 13 positive clones identified and reported here, it is worth of note that the interaction of HtrA1 with tubulin and collagen (extracellular matrix proteins) and with tuberin (cytoplasmic protein) is confirmed by other studies, and this further supports previous findings in which HtrA1 can be found active as an intracytoplasmic protein or as secreted protein as well

Neuronal LRP4 regulates synapse formation in the developing CNS

The low-density lipoprotein receptor-related protein 4 (LRP4) is essential in muscle fibers for the establishment of the neuromuscular junction. Here, we show that LRP4 is also expressed by embryonic cortical and hippocampal neurons, and that downregulation of LRP4 in these neurons causes a reduction in density of synapses and number of primary dendrites. Accordingly, overexpression of LRP4 in cultured neurons had the opposite effect inducing more but shorter primary dendrites with an increased number of spines. Transsynaptic tracing mediated by rabies virus revealed a reduced number of neurons presynaptic to the cortical neurons in which LRP4 was knocked down. Moreover, neuron-specific knockdown of LRP4 by in utero electroporation of LRP4 miRNA in vivo also resulted in neurons with fewer primary dendrites and a lower density of spines in the developing cortex and hippocampus. Collectively, our results demonstrate an essential and novel role of neuronal LRP4 in dendritic development and synaptogenesis in the CNS

Digital Twins for Health: Opportunities, Barriers and a Path Forward

The concept of precision medicine involves tailoring medical interventions to each patient’s specific needs, considering factors such as their genetic makeup, lifestyle, environment and response to therapies. The emergence of digital twin (DT) technology is anticipated to enable such customization. The healthcare field is, thus, increasingly exploring the use of digital twins (DTs), benefiting from successful proof of concept demonstrated in various industries. If their full potential is realized, DTs have the capability to revolutionize connected care and reshape the management of lifestyle, health, wellness and chronic diseases in the future. However, the realization of DTs’ full potential in healthcare is currently impeded by technical, regulatory and ethical challenges. In this chapter, we map the current applications of DTs in healthcare, with a primary focus on precision medicine. We also explore their potential applications in clinical trial design and hospital operations. We identify the key enablers of DTs in healthcare and discuss the opportunities and barriers that foster or hinder their larger and faster diffusion. By providing a comprehensive view of the current landscape, opportunities and challenges, we aim to contribute to DTs’ ongoing development and help policymakers facilitate the growth of DTs’ application in healthcare