Antibody Profiles According to Mild or Severe SARS-CoV-2 Infection,Atlanta, Georgia,USA, 2020

Among patients with coronavirus disease (COVID-19), IgM levels increased early after symptom onset for those with mild and severe disease, but IgG levels increased early only in those with severe disease. A similar pattern was observed in a separate serosurveillance cohort. Mild COVID-19 should be investigated separately from severe COVID-19.     

Flavonoids from Iris songarica and their antioxidant and estrogenic activity

A new dihydroflavonol, songaricol ( 1) and seven known flavonoids, ayamenin A ( 2), irisflavone A ( 3), 5,7-dihydroxy-2',6-dimethoxyisoflavone ( 4), irilin B ( 5), 5,3'-dihydroxy-7,8,2'-trimethoxyisoflavone ( 6) and irisoid A ( 7) were isolated from rhizome and roots of IRIS SONGARICA. Structure elucidation of 1 was achieved through extensive NMR and circular dichroism techniques. Compounds 1, 5 and 7 showed antioxidant activity in HL-60 cells (IC50 values of 21, 11 and 3.8 microg/mL), whereas 2, 5 and the previously isolated irisone B were able to show estrogenic response (EC50 values of 305.5, 159.7 and 322.0 microg/mL) in yeast cells expressing human estrogen receptor (ER-alpha).     

Risk assessments for the insect repellents DEET and picaridin

For the use of topical insect repellents, DEET and picaridin, human health risk assessments were conducted for various population subgroups. Acute, subchronic, and chronic dermal exposures were examined. No-observed-effect-levels (NOELs) of 200, 300, and 100mg/kg body weight (BW) were used as endpoints for DEET for acute, subchronic, and chronic exposures, respectively. For picaridin, a NOEL of 2000 mg/kg BW/day for acute exposure and a NOEL of 200 mg/kg BW/day for subchronic and chronic exposures were used. Daily exposures to several population subgroups were estimated. Risks were characterized using the Margin of Exposure (MOE) method (NOEL divided by the estimated exposure), whereby estimated MOEs were compared to an MOE of 100. Estimates of daily exposures ranged from 2 to 59 mg/kg BW/day for DEET and 2 to 22 mg/kg BW/day for picaridin. Children had the lowest MOEs. However, none of the estimated exposures exceeded NOELs for either repellent. At 40% DEET for acute exposure, children < or = 12 years had MOEs below 100. For subchronic and chronic exposures children at > or = 25% DEET and at 15% picaridin had MOEs below 100. Therefore, we found no significant toxicological risks from typical usage of these topical insect repellents.     

Renal fibrosis due to multiple cisplatin treatment is exacerbated by kinin B1 receptor antagonism

Cisplatin is a widely used chemotherapeutic drug, but its side effects are a major limiting factor. Nephrotoxicity occurs in one third of patients undergoing cisplatin treatment. The acute tubular injury caused by cisplatin often leads to a defective repair process, which translates into chronic renal disorders. In this way, cisplatin affects tubular cells, and maladaptive tubules regeneration will ultimately result in tubulointerstitial fibrosis. Kinins are well known for being important peptides in the regulation of inflammatory stimuli, and kinin B1 receptor deficiency and antagonism have been shown to be beneficial against acute cisplatin nephrotoxicity. This study aimed to analyze the effects of kinin B1 receptor deletion and antagonism against repeated cisplatin-induced chronic renal dysfunction and fibrosis. Both the deletion and the antagonism of B1 receptor exacerbated cisplatin-induced chronic renal dysfunction. Moreover, the inhibition of B1 receptor increased tubular injury and tubulointerstitial fibrosis after repeated treatment with cisplatin. The balance between M1/M2 macrophage polarization plays an important role in renal fibrosis. Kinin B1 receptor antagonism had no impact on M1 markers when compared to cisplatin. However, YM1, an M2 marker and an important molecule for the wound healing process, was decreased in mice treated with kinin B1 receptor antagonist, compared to cisplatin alone. Endothelin-1 levels were also increased in mice with B1 receptor inhibition. This study showed that kinin B1 receptor inhibition exacerbated cisplatin-induced chronic renal dysfunction and fibrosis, associated with reduced YM1 M2 marker expression, thus possibly affecting the wound healing process.     

A thermally responsive biopolymer conjugated to an acid-sensitive derivative of paclitaxel stabilizes microtubules, arrests cell cycle, and induces apoptosis

Poor aqueous solubility limits the therapeutic index of paclitaxel as an anti-cancer drug. Synthesis of soluble prodrugs of paclitaxel, or conjugation of the drug to macromolecular carriers have been reported to increase its water-solubility. Macromolecular drug carriers have an added advantage of targeting the drug to the tumor site due to the abnormal tumor blood and lymphatic vasculature. This study describes a thermally responsive macromolecular carrier, elastin-like polypeptide (ELP) for the delivery of paclitaxel. Paclitaxel was bound to ELP by conjugation with the 6-maleimidocaproyl hydrazone derivative of paclitaxel, an acid-sensitive paclitaxel prodrug, for the potential treatment of breast cancer. Focused hyperthermia above a specific transition temperature at the site of a tumor causes ELP to aggregate and accumulate, thereby increasing the local concentration of the drug cargo. The paclitaxel prodrug described here bears an acid-sensitive linker that is cleavable at the lysosomal/endosomal pH, which allows a controlled intracellular release of the drug. The ELP-delivered paclitaxel in the presence of hyperthermia inhibits MCF-7 cell proliferation by stabilizing the microtubule structures, arresting the cells at the G2/M stage, and inducing apoptosis in a manner similar to conventional paclitaxel. It also inhibits proliferation of a paclitaxel resistant MCF-7 cell line. These data provide an in vitro proof of concept for the use of ELP as a delivery vehicle of paclitaxel.     

Economic evaluation of multiplex ligation-dependent probe amplification and karyotyping in prenatal diagnosis: a cost-minimization analysis

Purpose  

To assess the cost-effectiveness of Multiplex Ligation-dependent Probe Amplification (MLPA, P095 kit) compared to karyotyping.