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Vitamin D is a steroid hormone that is essential for bone mineral metabolism and it has several other effects in the body, including anti-cancer actions. Vitamin D causes a reduction in cell growth by interrupting the cell cycle. Moreover, the active form of vitamin D, i.e., 1,25-dihydroxyvitamin D, exerts various effects via its interaction with the vitamin D receptor on the innate and adaptive immune system, which could be relevant in the onset of tumors. Multiple myeloma is a treatable but incurable malignancy characterized by the growth of clonal plasma cells in protective niches in the bone marrow. In patients affected by multiple myeloma, vitamin D deficiency is commonly correlated with an advanced stage of the disease, greater risk of progression, the development of pathological fractures, and a worse prognosis. Changes in the vitamin D receptor often contribute to the occurrence and progress of deficiencies, which can be overcome by supplementation with vitamin D or analogues. However, in spite of the findings available in the literature, there is no clear standard of care and clinical practice varies. Further research is needed to better understand how vitamin D influences outcomes in patients with monoclonal gammopathies.
The application of circulating tumor DNA (ctDNA) has been studied for predicting recurrent disease after surgery and treatment response during systemic treatment. Metastasectomy can be curative for well-selected patients with metastatic colorectal cancer (mCRC). This prospective study investigated the ctDNA level before and after metastasectomy in patients with mCRC to explore its potential as a predictive biomarker.
We collected data on 98 metastasectomies for mCRC performed from March 2017 to February 2020. Somatic mutations in the primary and metastatic tumors were identified and tumor-informed ctDNAs were selected by ultra-deep targeted sequencing. Plasma samples were mandatorily collected before and 3-4 weeks after metastasectomy and serially, if patients agreed.
Data on 67 of 98 metastasectomies (58 patients) meeting the criteria were collected. ctDNA was detected in 9 (29%) of 31 cases treated with upfront metastasectomy and in 7 (19.4%) of 36 cases treated with metastasectomy after upfront chemo making after metastasectomy for mCRC using ctDNA, further studies for improving specific outcomes are needed.This paper investigates the potential of the enzymatic management of high pH in white juice and wine using a combination of enzymes-glucose oxidase coupled with catalase. Catazyme® 25 L, a commercially available blend of the two enzymes, was added at different doses (0.2 g/L, 0.6 g/L, and 1g/L) to white grape juice and various parameters (glucose, gluconic acid, pH) were monitored over 24 h of treatment. Treated wines were fermented to dryness without any difficulty and the wines were chemically and sensorially evaluated. At the highest dose (1 g/L), pH was reduced from 3.9 to 3.2, with 20.5 g of gluconic acid produced, while at the lowest dose (0.2 g/L), pH decreased from 4.0 to 3.5 and 8.8 g of gluconic acid was produced. Flash profiling indicated that treated wines were lighter in color than the control and were described using terms such as floral, fruit, citrus, and sour while the control wine was described as being fermented, medicinal, pungent, and oxidized. In conclusion, glucose oxidase coupled with catalase was shown to be effective at significantly reducing juice and wine pH in a short amount of time and with a positive impact on the organoleptic profiles of the treated wines.Açaí berry is a fruit from the tree commonly known as açaízeiro (Euterpe oleracea Mart.) originated from the Amazonian region and widely consumed in Brazil. There are several reports of the anti-inflammatory activity of its pulp and few data about the seed's potential in inflammation control. This work aimed to evaluate the effect of catechin-rich açaí extract on lipopolysaccharide (LPS)-stimulated RAW 264.7 cells and carrageenan-induced paw edema. The treatment with E. oleracea ethyl acetate extract (EO-ACET) was used in an in vitro model performed with macrophages stimulated by LPS, in which pro-inflammatory markers were evaluated, and in an in vivo model of acute inflammation, in which edema inhibition was evaluated. EO-ACET showed an absence of endotoxins, and did not display cytotoxic effects in RAW 264.7 cells. LPS-stimulated cells treated with EO-ACET displayed low levels of nitrite and interleukins (IL's), IL-1β, IL-6 and IL-12, when compared to untreated cells. EO-ACET treatment was able to inhibit carrageenan-induced paw edema at 500 and 1000 mg/kg, in which no acute inflammatory reaction or low mast cell counts were observed by histology at the site of inoculation of λ-carrageenan. These findings provide more evidence to support further studies with E. oleracea seeds for the treatment of inflammation.The blue bream Ballerus ballerus (L.) is one of two species of the Ballerus genus occurring in Europe. The biotechnology for its reproduction under controlled conditions needs to be developed to conserve its local populations. Therefore, a range of experiments were performed to obtain valuable gametes from blue bream following hormonal stimulation with carp pituitary homogenate (CPH), Ovopel and Ovaprim. CPH and Ovopel were injected twice and Ovaprim-once, under a pectoral fin. The spawners were inspected 12 h after the last injection, and the gametes were collected. Eggs were collected from spawning females and fertilized with sperm from three males. The smallest number of ovulating blue bream (four females) was obtained from individuals stimulated with Ovaprim. There were six to nine ovulating females in the other groups, accounting for 60-90% of the females in the respective groups. The latency period was the shortest in the spawners stimulated with Ovopel. The fish in this group ovulated 14 h after the hormonal injection. Spawning was synchronized and all females spawned simultaneously. The highest average weight of eggs per fish (75.4 g) was obtained from the females stimulated with Ovopel, whereas the individuals stimulated with Ovaprim provided the smallest average amount of eggs (49.5 g). The study showed that blue bream spawners are not very sensitive to reproduction-related handling under controlled conditions.We investigate the effect of the intrinsic interlayers on the diffusion assisted bonding properties of the austenitic steel (stainless steel 316L) and ferric steels (Low-carbon steel Q345R) in a hot rolling process by molecular dynamics simulations and experiment. The introduction of an intrinsic interlayer (Cr or Ni) widens the diffusion region, leading to enhancement of bonding. The thickness of the diffusion region enlarges with an increase of temperature, with an enhancement factor of 195% and 108%, for Cr and Ni interlayer, respectively, at the temperature of 1800 K. Further diffusion analysis reveals the unsymmetrical diffusion near the interface. Our experimental investigation evidenced our computation discovery.Hospital staff are a priority target group in the European COVID-19 vaccination strategy. Measuring the extent of COVID-19 vaccination hesitancy and understanding the reasons behind it are essential to be able to tailor effective communication campaigns. Using the Health Belief Model (HBM) as a theoretical framework, a survey was conducted among staff members of a Belgian three-site hospital center between 6 and 20 January 2021. Multivariable logistic ordinal regression was performed to assess determinants of the attitude towards COVID-19 vaccination. Reasons for and against COVID-19 vaccination and the need for information were explored among hesitant staff members. Among the respondents (N = 1132), 58% and 4.9% said that they would certainly and certainly not get vaccinated, respectively; 37.1% were hesitant, with different degrees of certainty. A positive attitude towards COVID-19 vaccination was associated with being older, being a physician, being vaccinated against seasonal flu, and with several HBM factors (including perceived benefits and cues to actions). Among hesitant staff, concerns about potential side effects and the impression that the vaccine was developed too quickly were the main reasons against COVID-19 vaccination. The key factors in the decision process were data on vaccine efficacy and safety, and knowing that vaccination went well in others. PNT-737 These data are helpful to further tailor the communication campaign and ensure sufficient vaccination coverage among hospital staff.The current study systematically reviewed, summarized and meta-analyzed the clinical features of the vaccines in clinical trials to provide a better estimate of their efficacy, side effects and immunogenicity. All relevant publications were systematically searched and collected from major databases up to 12 March 2021. A total of 25 RCTs (123 datasets), 58,889 cases that received the COVID-19 vaccine and 46,638 controls who received placebo were included in the meta-analysis. In total, mRNA-based and adenovirus-vectored COVID-19 vaccines had 94.6% (95% CI 0.936-0.954) and 80.2% (95% CI 0.56-0.93) efficacy in phase II/III RCTs, respectively. Efficacy of the adenovirus-vectored vaccine after the first (97.6%; 95% CI 0.939-0.997) and second (98.2%; 95% CI 0.980-0.984) doses was the highest against receptor-binding domain (RBD) antigen after 3 weeks of injections. The mRNA-based vaccines had the highest level of side effects reported except for diarrhea and arthralgia. Aluminum-adjuvanted vaccines had the lowest systemic and local side effects between vaccines' adjuvant or without adjuvant, except for injection site redness. The adenovirus-vectored and mRNA-based vaccines for COVID-19 showed the highest efficacy after first and second doses, respectively. The mRNA-based vaccines had higher side effects. Remarkably few experienced extreme adverse effects and all stimulated robust immune responses.Corneal endothelial dystrophy is a relevant cause of vision loss and corneal transplantation worldwide. In the present study, we analyzed the effect of mesenchymal stem cell (MSC)-derived extracellular vesicles (MSC-EVs) in an in vitro model of corneal dystrophy, characterized by endoplasmic reticulum stress. The effects of MSC-EVs were compared with those of serum-derived EVs, reported to display a pro-angiogenic activity. MSC-EVs were able to induce a significant down-regulation of the large majority of endoplasmic reticulum stress-related genes in human corneal endothelial cells after exposure to serum deprivation and tunicamycin. In parallel, they upregulated the Akt pathway and limited caspase-3 activation and apoptosis. At variance, the effect of the serum EVs was mainly limited to Akt phosphorylation, with minimal or absent effects on endoplasmic reticulum stress modulation and apoptosis prevention. The effects of MSC-EVs were correlated to the transfer of numerous endoplasmic reticulum (ER)-stress targeting miRNAs to corneal endothelial cells. These data suggest a potential therapeutic effect of MSC-EVs for corneal endothelial endoplasmic reticulum stress, a major player in corneal endothelial dystrophy.
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