Genetic control of cadmium tolerance in Drosophila melanogaster.

Files from a transgenic line of Drosophila melanogaster with two copies of the metallothionein allele Mtn3 were more tolerant to cadmium than strains with only one copy of the gene. However, flies with the Mtn3 allele were as tolerant as flies with the Mtn3 allele, despite the level of expression of Mtn3 being three times higher than of Mtn3. We propose that the substitution of Lys-40 (in Mtn3) for Glu-40 (in Mtn1) accounts for a reduction in binding affinity of Mtn1, which offsets the increased expression levels

Kidney transplantation with presymptomatic COVID-19–positive surgeon

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Local structural studies of Ba1−x_{1-x}Kx_xFe2_2As2_2 using atomic pair distribution function analysis

Systematic local structural studies of Ba$_{1-x}$K$_x$Fe$_2$As$_2$ system are undertaken at room temperature using atomic pair distribution function (PDF) analysis. The local structure of the Ba$_{1-x}$K$_x$Fe$_2$As$_2$ is found to be well described by the long-range structure extracted from the diffraction experiments, but with anisotropic atomic vibrations of the constituent atoms ($U_{11}$ = $U_{22} \ne U_{33}$). The crystal unit cell parameters, the FeAs$_4$ tetrahedral angle and the pnictogen height above the Fe-plane are seen to show systematic evolution with K doping, underlining the importance of the structural changes, in addition to the charge doping, in determining the properties of Ba$_{1-x}$K$_x$Fe$_2$As$_2$

Gastroresistant capsular device prepared by injection molding

In the present work, the possibility of manufacturing by injection molding (IM) a gastro-resistant capsular device based on hydroxypropyl methyl cellulose acetate succinate (HPMCAS) was investigated. By performing as an enteric soluble container, such a device may provide a basis for the development of advantageous alternatives to coated dosage forms. Preliminarily, the processability of the selected thermoplastic polymer was evaluated, and the need for a plasticizer (polyethylene glycol 1500) in order to counterbalance the glassy nature of the molded items was assessed. However, some critical issues related to the physical/mechanical stability (shrinkage and warpage) and opening time of the device after the pH change were highlighted. Accordingly, an in-depth formulation study was carried out taking into account differing release modifiers potentially useful for enhancing the dissolution/disintegration rate of the capsular device at intestinal pH values. Capsule prototypes with thickness of 600 and 900 \u3bcm containing Kollicoat\uae IR and/or Explotab\uae CLV could be manufactured, and a promising performance was achieved with appropriate gastric resistance in pH 1.2 medium and break-up in pH 6.8 within 1 h. These results would support the design of a dedicated mold for the development of a scalable manufacturing process

Evaluation of Hot-Melt Extrusion and Injection Molding for Continuous Manufacturing of Immediate-Release Tablets

The exploitation of hot-melt extrusion and injection molding for the manufacturing of immediate-release (IR) tablets was preliminarily investigated in view of their special suitability for continuous manufacturing, which represents a current goal of pharmaceutical production because of its possible advantages in terms of improved sustainability. Tablet-forming agents were initially screened based on processability by single-screw extruder and micromolding machine as well as disintegration/dissolution behavior of extruded/molded prototypes. Various polymers, such as low-viscosity hydroxypropylcellulose, polyvinyl alcohol, polyvinyl alcohol-polyethylene glycol graft copolymer, various sodium starch glycolate grades (e.g., Explotab\uae CLV) that could be processed with no need for technological aids, except for a plasticizer, were identified. Furthermore, the feasibility of both extruded and molded IR tablets from low-viscosity hydroxypropylcellulose or Explotab\uae CLV was assessed. Explotab\uae CLV, in particular, showed thermoplastic properties and a very good aptitude as a tablet-forming agent, starting from which disintegrating tablets were successfully obtained by either techniques. Prototypes containing a poorly soluble model drug (furosemide), based on both a simple formulation (Explotab\uae CLV and water/glycerol as plasticizers) and formulations including dissolution/disintegration adjuvants (soluble and effervescent excipients) were shown to fulfill the USP 37 dissolution requirements for furosemide tablets

The perceived ability of gastroenterologists, hepatologists and surgeons can bias medical decision making

Medical errors are a troubling issue and physicians should be careful to scrutinize their own decisions, remaining open to the possibility that they may be wrong. Even so, doctors may still be overconfident. A survey was here conducted to test how medical experience and self-confidence can affect physicians working in the specific clinical area. Potential participants were contacted through personalized emails and invited to contribute to the survey. The \u201crisk-intelligence\u201d test consists of 50 statements about general knowledge in which participants were asked to indicate how likely they thought that each statement was true or false. The risk-intelligence quotient (RQ), a measure of self-confidence, varies between 0 and 100. The higher the RQ score, the better the confidence in personal knowledge. To allow for a representation of 1000 physicians, the sample size was calculated as 278 respondents. A total of 1334 individual emails were sent to reach 278 respondents. A control group of 198 medical students were also invited, of them, 54 responded to the survey. The mean RQ (SD)of physicians was 61.1 (11.4) and that of students was 52.6 (9.9). Assuming age as indicator of knowledge, it was observed that physicians 6434 years had a mean RQ of 59.1 (10.1); those of 35\u201342 years had 61.0 (11.0); in those of 43\u201351 years increased to 62.9 (12.2); reached a plateau of 63.0 (11.5) between 52\u201359 years and decreased to 59.6 (12.1) in respondents 6560 years (r2:0.992). Doctors overestimate smaller probabilities and under-estimate higher probabilities. Specialists in gastroenterology and hepato-biliary diseases suffer from some degree of self-confidence bias, potentially leading to medical errors. Approaches aimed at ameliorating the self-judgment should be promoted more widely in medical education

On Fourier integral transforms for qq-Fibonacci and qq-Lucas polynomials

We study in detail two families of $q$-Fibonacci polynomials and $q$-Lucas polynomials, which are defined by non-conventional three-term recurrences. They were recently introduced by Cigler and have been then employed by Cigler and Zeng to construct novel $q$-extensions of classical Hermite polynomials. We show that both of these $q$-polynomial families exhibit simple transformation properties with respect to the classical Fourier integral transform

Effects of Heavy Metals on Drosophila Larvae and a Metallothionein cDNA

Drosophila melanogaster larvae reared on food containing radioactive cadmium retained over 80% of it, mostly in the intestinal epithelium. The majority of this radioactivity was associated with a soluble protein of less than 10,000 molecular weight. Synthesis of this cadmium-binding protein was induced by the metal as demonstrated by incorporation of radioactive cysteine. Most copper ingested by larvae was also found to associate with a low molecular weight, inducible protein, but some of it was found in an insoluble fraction. Zinc was unable to, or very inefficient at, binding or inducing the synthesis of a similar protein. A D. melanogaster cDNA clone was isolated based on its more intense hybridization to copies of RNA sequences from copper-fed larvae than from control larvae. This clone showed strong hybridization to mouse metallothionein-I cDNA at reduced stringency. Its nucleotide sequence includes an open-reading segment which codes for a 40-amino acid protein; this protein was identified as metallothionein based on its similarity to the amino-terminal portion of mammalian and crab metalloproteins. The ten cysteine residues present occur in five pairs of near-vicinal cysteines (Cys-X-Cys). This cDNA sequence hybridized to a 400-nucleotide polyadenylated RNA whose presence in the cells of the alimentary canal of larvae was stimulated by ingestion of cadmium or copper; in other tissues this RNA was present at much lower levels. Mercury, silver, and zinc induced metallothionein to a lesser extent. Whether (any of) the protein(s) discussed above correspond(s) to that coded by this RNA sequence has not yet been determined.ImagesFIGURE 2.FIGURE 6.FIGURE 9

Normothermic and hypothermic oxygenated perfusion for donation after circulatory death in kidney transplantation: Do we pay higher risk of severe infection after transplantation?: A case report

Background: Normothermic and hypothermic oxygenated perfusion for donation after circulatory death in kidney transplantation are becoming popular in Italy, with the purpose of reducing the risk of primary non function and delayed graft function due to the prolonged warm ischemia time. Potential complications related to these procedures are currently under investigation and are continuously emerging with the increasing experience. Post-operative infections - in particular graft arteritis - are a rare complication but determine high risk of mortality and of graft loss. The acute onset of the arterial complications makes it very difficult to find an effective treatment, and early diagnosis is crucial for saving both patient and graft. Prevention of such infections in this particular setting are advisable. Case presentation: We present a patient with an acute arterial rupture after transplantation of a DCD graft treated in-vivo hypothermic oxygenated perfusion. The cause was a severe arteritis of the renal artery caused by Candida krusei and Pseudomonas aeruginosa. We discussed our treatment and we compared it to the other reported series. Conclusion: Fungal infections in DCD transplant may be treacherous and strategies to prevent them should be advocated

Molecular basis of anti-inflammatory action of platelet rich plasma on human chondrocytes : mechanisms of NF-kB inhibition via HGF

Loss of articular cartilage through injury or disease presents major clinical challenges also because cartilage has very poor regenerative capacity, giving rise to the development of biological approaches. As autologous blood product, platelet-rich plasma (PRP) provides a promising alternative to surgery by promoting safe and natural healing. Here we tested the possibility that PRP might be effective as an anti-inflammatory agent, providing an attractive basis for regeneration of articular cartilage, and two principal observations were done. First, activated PRP in chondrocytes reduced the transactivating activity of NF-kB, critical regulator of the inflammatory process, and decreased the expression of COX2 and CXCR4 target genes. By analyzing a panel of cytokines with different biological significance, in activated PRP we observed increases in hepatocyte growth factor (HGF), interleukin-4 and tumor necrosis factor-alpha (TNF-alpha). HGF and TNF-alpha, by disrupting NF-kB-transactivating activity, were important for the anti-inflammatory function of activated PRP. The key molecular mechanisms involved in PRP-inhibitory effects on NF-kB activity were for HGF the enhanced cellular IkBalpha expression, that contributed to NF-kB-p65 subunit retention in the cytosol and nucleo-cytoplasmic shuttling, and for TNF-alpha the p50/50 DNA-binding causing inhibition of target-gene expression. Second, activated PRP in U937-monocytic cells reduced chemotaxis by inhibiting chemokine transactivation and CXCR4-receptor expression, thus possibly controlling local inflammation in cartilage. In conclusion, activated PRP is a promising biological therapeutic agent, as a scaffold in micro-invasive articular cartilage regeneration, not only for its content of proliferative/differentiative growth factors, but also for the presence of anti-inflammatory agents including HGF