Follicular thyroid carcinoma: Differences in clinical relevance between minimally invasive and widely invasive tumors

Evidence on the biological behavior and clinical courses of minimally invasive and widely invasive follicular thyroid carcinoma (MI-FTC, WI-FTC) is still debatable. The current study was conducted to identify differences between MI and WI tumors and those prognostic parameters influencing late outcome such as local recurrence and survival

From mining wastes to mineral sources - investigating the REE-bearing occurrences in the Arburèse District (SW Sardinia)

In recent years, the search for possible sources of REE minerals in Europe involved numerous old mine areas with high volumes of mining wastes that may offer significant amounts of Critical Raw Materials (CRMs). In some cases, strong evidence of CRMs anomalous concentrations arises from environmental characterization of wastes, so that an interesting problem is that of finding their sources, i.e., the original CRMs - rich mineral phases in the residual ore. An excellent example is provided by the Arburèse district of SW Sardinia, for about 150 years a major Pb-Zn source in Italy, now an area under study for remediation of its severe environmental problems, including >10 Mt of waste deposits. The district exploited a large system (>10 km) of low-temperature polymetallic veins hosted in Lower Paleozoic siliciclastic rocks belonging to the Variscan Nappe zone, arranged in two main geometrical trends relative to the late Variscan Arbus pluton: “peripheral” and “intersecting”. Recent investigations in the Montevecchio mine area discovered high Zn (up to 2.65 wt.%) and Pb (1.23 wt.%) grades in stratified tailing materials belonging to the Sanna old processing plant. Remarkably, ICP-MS analyses on the same materials revealed total REE+ Y contents attaining about 600 ppm. XRD studies confirmed a tailing composition essentially made of gangue minerals (quartz, siderite and micas) with goethite, baryte and traces of Zn carbonates and Pb sulfates. Chondrite-normalized REE patterns are coherent with the hydrothermal character of the source: however, both the REE mineralogical host(s) in tailings and in the Montevecchio ore are still undetermined. In the search of REE-bearing phases in the ores, some relevant insights are provided by studies on the southern branch of the Arburèse system, where the veins of “peripheral” system are hosted in late Ordovician-Silurian sedimentary sequences. In this part of the district the polymetallic veins assume the character of five-elements (Ni-Co-As-Bi-Ag) veins, with a rich Ni-Co-Fe arsenide – quartz association (1) overprinted by a Zn-Pb-Cu sulfide – siderite – quartz association (2), very similar to that dominating in Montevecchio. Investigations in the Pira Inferida mine sector highlighted the presence of LREE fluorocarbonates (synchysite-Ce and bastnaesite-Ce) and phosphates (monazite) associated with rutile and apatite. LREE minerals have been detected by SEM-EDS as tiny crystals in the quartz-sericitic gangue of the Montevecchio-type (2) mineral association. The same minerals are found in millimetric aggregates in the oxide zone of the veins, sporadically reported by mineral collectors in other mine sites of the same system. Overall, these occurrences, similar to those found in other low-temperature vein systems of Sardinia (e.g., Silius vein system), appear reliable mineral REE sources for Montevecchio mine wastes; they may be therefore used as proxies for REE exploration and assessment in the district

MF59®-Adjuvanted H5N1 Vaccine Induces Immunologic Memory and Heterotypic Antibody Responses in Non-Elderly and Elderly Adults

Pathogenic avian influenza virus (H5N1) has the potential to cause a major global pandemic in humans. Safe and effective vaccines that induce immunologic memory and broad heterotypic response are needed.Healthy adults aged 18-60 and > 60 years (n = 313 and n = 173, respectively) were randomized (1:1) to receive two primary and one booster injection of 7.5 microg or 15 microg doses of a subunit MF59-adjuvanted H5N1 (A/Vietnam/1194/2004) (clade 1) vaccine. Safety was monitored until 6 months after booster. Immunogenicity was assessed by hemagglutination inhibition (HI), single radial hemolysis (SRH) and microneutralization assays (MN). Mild injection-site pain was the most common adverse reaction. No serious adverse events relating to the vaccine were reported. The humoral immune responses to 7.5 microg and 15 microg doses were comparable. The rates for seroprotection (HI>40; SRH>25 mm(2); MN > or = 40) after the primary vaccination ranged 72-87%. Six months after primary vaccination with the 7.5 microg dose, 18% and 21% of non-elderly and elderly adults were seroprotected; rates increased to 90% and 84%, respectively, after the booster vaccination. In the 15 microg group, seroprotection rates among non-elderly and elderly adults increased from 25% and 62% after primary vaccination to 92% and 88% after booster vaccination, respectively. A heterologous immune response to the H5N1/turkey/Turkey/05 strain was elicited after second and booster vaccinations.Both formulations of MF59-adjuvanted influenza H5N1 vaccine were well tolerated. The European Union requirement for licensure for pre-pandemic vaccines was met by the lower dose tested. The presence of cross-reactive antibodies to a clade 2 heterologous strain demonstrates that this vaccine may be appropriate for pre-pandemic programs.(ClinicalTrials.gov) NCT00311480

Prioritizing management actions for invasive non-native plants through expert-based knowledge and species distribution models

Given the high number of non-native plants that are being introduced worldwide and the time required to process formal pest risk analyses, a framework for the prioritization of management actions is urgently required. We therefore propose a framework for a replicable and standardized prioritization for management actions (eradication, control and monitoring) of invasive non-native plants, combining expert knowledge, current and future climatic suitability estimated by species distribution models (SDMs), clustering and ordination techniques. Based on expert consultation and using Italy as case study, invasive non-native plant species were selected and three categories of management actions were identified: eradication, control and containment, and monitoring. Finally, two further classes of priorities were proposed for each of the management actions: “high” and “low” priority. Overall, SDMs highlighted a high and very high suitability for Continental and Mediterranean bioregions for most invasive plants. Cluster analysis revealed three distinct clusters with varying levels of suitability for the Italian bioregions. Cluster 1 exhibited a higher suitability across all Italian bioregions, whereas non-native plants grouped in Cluster 2 predominantly featured high suitability in Mediterranean areas. Finally, Cluster 3 showed the lowest suitability values. Two ordination analysis highlighted the variability in bioclimatic suitability for each non-native plant within each cluster, as well as their current distribution pattern. Lastly, a third ordination, integrating bioclimatic suitability and spatial patterns, has allowed the differentiation of management actions for each non-native plant at both national and bioregional scales. Specifically, seven non-native plants were earmarked for eradication action, six for monitoring action, while the remaining species were deemed suitable for control and containment. Our results and the methodology proposed meet the demand for replicable new early warning tools; that is to predict the location of new outbreaks, to establish priorities for eradication, control and containment, and to monitor invasive non-native species

Control of neoclassical tearing modes by Sawtooth control

The onset of a neoclassical tearing mode (NTM) depends on the existence of a large enough seed island. It is shown in the Joint European Torus that NTMs can be readily destabilized by long-period sawteeth, such as obtained by sawtooth stabilization from ion-cyclotron heating or current drive. This has important implications for burning plasma scenarios, as alpha particles strongly stabilize the sawteeth. It is also shown that, by adding heating and current drive just outside the inversion radius, sawteeth are destabilized, resulting in shorter sawtooth periods and larger beta values being obtained without NTMs

Apotopes and the biliary specificity of primary biliary cirrhosis

Primary biliary cirrhosis (PBC) is characterized by antimitochondrial antibodies (AMAs), directed to the E2 component of the pyruvate dehydrogenase complex (PDC-E2). Notwithstanding the presence of mitochondria in virtually all nucleated cells, the destruction in PBC is limited to small intrahepatic bile ducts. The reasons for this tissue specificity remain unknown, although biliary epithelia cells (BECs) uniquely preserve the PDC-E2 epitope following apoptosis. Notably, PBC recurs in an allogeneic transplanted liver, suggesting generic rather than host PBC-specific susceptibility of BEC. We used cultured human intrahepatic BECs (HIBECs) and other well-characterized cell lines, including, HeLa, CaCo-2 cells, and nontransformed human keratinocytes and bronchial epithelial cells, to determine the integrity and specific localization of PDC-E2 during induced apoptosis. All cell lines, both before and after apoptosis, were tested with sera from patients with PBC (n = 30), other autoimmune liver and rheumatic diseases (n = 20), and healthy individuals (n = 20) as well as with a mouse monoclonal antibody against PDC-E2 and AMA with an immunoglobulin A isotype. PDC-E2 was found to localize unmodified within apoptotic blebs of HIBECs, but not within blebs of various other cell lineages studied. The fact that AMA-containing sera reacted with PDC-E2 on apoptotic BECs without a requirement for permeabilization suggests that the autoantigen is accessible to the immune system during apoptosis. Conclusion: Our data indicate that the tissue (cholangiocyte) specificity of the autoimmune injury in PBC is a consequence of the unique characteristics of HIBECs during apoptosis and can be explained by exposure to the immune system of intact immunoreactive PDC-E2 within apoptotic blebs

The impact of COVID-19 on kidney transplant recipients in pre-vaccination and delta strain era: a systematic review and meta-analysis

Herein, we performed a meta-analysis of published clinical outcomes of corona virus disease 2019 (COVID-19) in hospitalized kidney transplant recipients. A systematic database search was conducted between December 1, 2019 and April 20, 2020. We analyzed 48 studies comprising 3137 kidney transplant recipients with COVID-19. Fever (77%), cough (65%), dyspnea (48%), and gastrointestinal symptoms (28%) were predominant on hospital admission. The most common comorbidities were hypertension (83%), diabetes mellitus (34%), and cardiac disease (23%). The pooled prevalence of acute respiratory distress syndrome and acute kidney injury were 58% and 48%, respectively. Invasive ventilation and dialysis were required in 24% and 22% patients, respectively. In-hospital mortality rate was as high as 21%, and increased to over 50% for patients in intensive care unit (ICU) or requiring invasive ventilation. Risk of mortality in patients with acute respiratory distress syndrome (ARDS), on mechanical ventilation, and ICU admission was increased: OR = 19.59, OR = 3.80, and OR = 13.39, respectively. Mortality risk in the elderly was OR = 3.90; however, no such association was observed in terms of time since transplantation and gender. Fever, cough, dyspnea, and gastrointestinal symptoms were common on admission for COVID-19 in kidney transplant patients. Mortality was as high as 20% and increased to over 50% in patients in ICU and required invasive ventilation

Dolichol: A Component of the Cellular Antioxidant Machinery

Dolichol, an end product of the mevalonate pathway, has been proposed a biomarker of aging, but its biological role, not to mention its catabolism, has not been fully understood. UV-B radiation was used to induce oxidative stress in isolated rat hepatocytes by the collagenase method. Effects on dolichol, phospholipids-bound polyunsaturated fatty acids (PL PUFA) and known lipid soluble antioxidants [coenzyme Q (CoQ) and α-tocopherol] were studied. The increase in oxidative stress was detected by a probe sensitive to reactive oxygen species (ROS). Peroxidation of lipids was assessed by measuring the release of thiobarbituric acid reactive substances (TBARS). Dolichol, CoQ and α-tocopherol were assessed by high-pressure liquid chromatography (HPLC), PL PUFA by gas-liquid chromatography (GC). UV-B radiation caused an immediate increase in ROS as well as lipid peroxidation and a simultaneous decrease in the levels of dolichol and lipid soluble antioxidants. Decrease in dolichol paralleled changes in CoQ levels and was smaller than that in α-tocopherol. The addition of mevinolin, a competitive inhibitor of the enzyme 3-hydroxy-3-methylglutaryl CoA reductase (HMG-CoAR), magnified the loss of dolichol and was associated with an increase in TBARS production. Changes in PL PUFA were minor. These findings highlight that oxidative stress has very early and similar effects on dolichol and lipid soluble antioxidants. Lower levels of dolichol are associated with enhanced peroxidation of lipids, which suggest that dolichol may have a protective role in the antioxidant machinery of cell membranes and perhaps be a key to understanding some adverse effects of statin therapy

An Efficient Vector System to Modify Cells Genetically

The transfer of foreign genes into mammalian cells has been essential for understanding the functions of genes and mechanisms of genetic diseases, for the production of coding proteins and for gene therapy applications. Currently, the identification and selection of cells that have received transferred genetic material can be accomplished by methods, including drug selection, reporter enzyme detection and GFP imaging. These methods may confer antibiotic resistance, or be disruptive, or require special equipment. In this study, we labeled genetically modified cells with a cell surface biotinylation tag by co-transfecting cells with BirA, a biotin ligase. The modified cells can be quickly isolated for downstream applications using a simple streptavidin bead method. This system can also be used to screen cells expressing two sets of genes from separate vectors

Source control in emergency general surgery: WSES, GAIS, SIS-E, SIS-A guidelines

Intra-abdominal infections (IAI) are among the most common global healthcare challenges and they are usually precipitated by disruption to the gastrointestinal (GI) tract. Their successful management typically requires intensive resource utilization, and despite the best therapies, morbidity and mortality remain high. One of the main issues required to appropriately treat IAI that differs from the other etiologies of sepsis is the frequent requirement to provide physical source control. Fortunately, dramatic advances have been made in this aspect of treatment. Historically, source control was left to surgeons only. With new technologies non-surgical less invasive interventional procedures have been introduced. Alternatively, in addition to formal surgery open abdomen techniques have long been proposed as aiding source control in severe intra-abdominal sepsis. It is ironic that while a lack or even delay regarding source control clearly associates with death, it is a concept that remains poorly described. For example, no conclusive definition of source control technique or even adequacy has been universally accepted. Practically, source control involves a complex definition encompassing several factors including the causative event, source of infection bacteria, local bacterial flora, patient condition, and his/her eventual comorbidities. With greater understanding of the systemic pathobiology of sepsis and the profound implications of the human microbiome, adequate source control is no longer only a surgical issue but one that requires a multidisciplinary, multimodality approach. Thus, while any breach in the GI tract must be controlled, source control should also attempt to control the generation and propagation of the systemic biomediators and dysbiotic influences on the microbiome that perpetuate multi-system organ failure and death. Given these increased complexities, the present paper represents the current opinions and recommendations for future research of the World Society of Emergency Surgery, of the Global Alliance for Infections in Surgery of Surgical Infection Society Europe and Surgical Infection Society America regarding the concepts and operational adequacy of source control in intra-abdominal infections