A Feasibility Study of High-Entropy Alloy Coating Deposition by Detonation Spraying Combined with Laser Melting

In this work, a new two-stage approach to the deposition of high-entropy alloy coatings is proposed. At the first stage, a composite precursor coating is formed by detonation spraying of the metal powder mixtures. At the second stage, the precursor coating is re-melted by a laser, and the formation of multi-component solid solution phases can be expected upon solidification. The feasibility of the proposed approach was validated using three different mixtures of Fe, Ni, Cu, Co and Al powders. It was shown that detonation spraying allows forming composite coatings with a uniform distribution of the lamellae of different metals. The results of the structural analysis of the laser-treated coatings suggest that complete alloying occurred in the melt and face-centered cubic solid solutions formed in the coatings upon cooling.     

Transmission of Diverse Variants of Strawberry Viruses Is Governed by a Vector Species

Advances in high-throughput sequencing methods have boosted the discovery of multistrain viral infections in diverse plant systems. This phenomenon appears to be pervasive for certain viral species. However, our knowledge of the transmission aspects leading to the establishment of such mixed infections is limited. Recently, we reported a mixed infection of a single strawberry plant with strawberry mottle virus (SMoV), strawberry crinkle virus (SCV) and strawberry virus 1 (StrV-1). While SCV and StrV-1 are represented by two and three molecular variants, respectively, SmoV has three different RNA1 and RNA2 segments. In this study, we focus on virus acquisition by individual adult aphids of the Aphis gossypii, Aphis forbesi and Chaetosiphon fragaefolii species. Single-aphid transmission trials are performed under experimental conditions. Both different viruses and individual virus strains show varying performances in single aphid acquisition. The obtained data suggests that numerous individual transmission events lead to the establishment of multistrain infections. These data will be important for the development of epidemiological models in plant virology.     

The Antifungal Itraconazole Is a Potent Inhibitor of Chikungunya Virus Replication

Chikungunya virus (CHIKV) is the causative agent of chikungunya fever, a disabling disease that can cause long-term severe arthritis. Since the last large CHIKV outbreak in 2015, the reemergence of the virus represents a serious public health concern. The morbidity associated with viral infection emphasizes the need for the development of specific anti-CHIKV drugs. Herein, we describe the development and characterization of a CHIKV reporter replicon cell line and its use in replicon-based screenings. We tested 960 compounds from MMV/DNDi Open Box libraries and identified four candidates with interesting antiviral activities, which were confirmed in viral infection assays employing CHIKV-nanoluc and BHK-21 cells. The most noteworthy compound identified was itraconazole (ITZ), an orally available, safe, and cheap antifungal, that showed high selectivity indexes of >312 and >294 in both replicon-based and viral infection assays, respectively. The antiviral activity of this molecule has been described against positive-sense single stranded RNA viruses (+ssRNA) and was related to cholesterol metabolism that could affect the formation of the replication organelles. Although its precise mechanism of action against CHIKV still needs to be elucidated, our results demonstrate that ITZ is a potent inhibitor of the viral replication that could be repurposed as a broad-spectrum antiviral.     

Pregnancy outcome after gestational exposure to the new macrolides: a prospective multi-center observational study

Objectives

To determine whether the use of the new macrolides (azithromycin, clarithromycin, roxithromycin) during the first trimester of pregnancy is associated with an increased risk of major malformations.

Study design

In a prospective multi-center study, pregnancy outcome was compared between pregnant women exposed to one of the new macrolides during the first trimester of pregnancy and two comparison groups one exposed to other antibiotics and the other to other non-teratogenic medications. All women enrolled in the study called one of the three participating teratogen information services (TIS). Group 1 macrolides (n = 161), group 2 other antibiotics (n = 213) and group 3 non-teratogens (n = 740).

Results

A total of 161 women exposed to the new macrolides (118 were exposed in the first trimester of pregnancy) and 953 from a comparison groups were followed up. The rate of major malformations in the study group was 4.1% compared to 2.1% in the other antibiotics exposed group (OR = 1.41, 95% CI 0.47–4.23) and 3.0% in the non-teratogens exposed group. The rate of elective terminations of pregnancy was significantly higher in the exposed group in compare to both comparison groups.

Conclusion

Our study, although relatively small sized, suggests that the use of the new macrolides during the first trimester of pregnancy does not represent an increased risk for congenital malformations strong enough for an induced abortion after such an exposure. Elective terminations of pregnancy because of early exposure to these medications should be reconsidered.     

Genetic polymorphisms in vasoactive genes and preeclampsia: a meta-analysis

There are controversies in reports on the association of polymorphisms in endothelial nitric oxide synthase, angiotensinogen, angiotensin receptor type 1 and angiotensin-converting enzyme genes with an increased risk of developing preeclampsia. We performed a systematic search of published case-control studies through the PubMed database up to January 2006, and report the results of a meta-analysis of polymorphisms investigated in more than five studies: Glu298Asp in eNOS gene (9 analyses involving 1055 patients and 1788 controls), Met235Thr in AGT gene (13 analyses involving 1128 patients and 2278 controls), and intron 16 insertion-deletion polymorphism in ACE gene (10 analyses involving 1121 patients and 1361 controls). Statistically significant associations with preeclampsia were identified for the Met235Thr/AGT polymorphism: OR 1.65 (95% CI 1.19, 2.29) if the polymorphism is considered under the dominant genetic model, and OR 1.54 (95% CI 1.12, 2.11) under the recessive model. For insertion-deletion/ACE polymorphism, statistical significance was demonstrated when the polymorphism was considered under the recessive model: OR 1.51 (95% CI 1.17, 1.94). No single polymorphism was identified as having a major effect.     

Molecular characteristics of rifampin and isoniazid resistant Mycobacterium tuberculosis strains from Beijing, China

Background China is one of the high burden countries of Mycobacterium tuberculosis （TB） infection globally, with high incidence and mortality. We studied the molecular characteristics of rifampin （RIF） and isoniazid （INH） resistant Mycobacterium tuberculosis strains from Beijing, China, in order to find out the genetic marker for rapid detection of specific drug resistance. Methods Forty pansusceptible and 81 resistant strains of Mycobacterium tuberculosis isolated from Beijing, China during 2002-2005 were analyzed. The modified rifampin oligonucleotide （RIFO） assay based on reverse line blot hybridization was used to detect mutations in the 81 bp hot-spot region of rpoB gene, which is associated with RIF resistance. The INH resistance associated genes, regulatory region mab-inhA （-15C/T） and structural gene katG S315T were detected by reverse line blot hybridization and PCR-restriction fragment length polymorphism （RFLP） method respectively. All the strains were typed by spoligotying and the Beijing genotype was further subdivided by NTF locus analysis. The distribution of drug resistance associated mutations in the above genes was compared in these groups. Results Sixty-five （91.5%） of 71 RIF resistant and 52 （92.9%） of 56 multidrug-resistant （MDR, i.e. resistant to at least RIF and INH） strains were found to harbor mutations in the rpoB hot-spot region. No mutation was detected in RIF sensitive strains. The specificity and sensitivity of the modified RIFO assay were 100% and 91.5%, respectively, katG315 AGC〉ACC and inhA-15C〉T mutations were found in 40 （60.6%） and 10 （15.2%） of 66 INH resistant strains, respectively; 7.6% of INH-resistant strains had mutations in both of these genes. Therefore, a combined use of both katG315 and inhA-15 identified 68.2% of INH-resistant strains. The Beijing genotype accounted for 91.7% of total strains and was further subdivided into ＂modern＂ （76.6%） and ＂ancestral＂ （23.4%） group. There is no significant difference between ＂ancestral＂ and ＂modern＂ group in prevalance of drug resistance-associated gene mutations. Conclusions The hot-spot region of rpoB gene can be used as genetic marker for detection of RIF resistant strains; a combined use of both katG315 and inhA-15 can improve the detection rate of I NH resistant strains; the Beijing genotype is prevalent in Beijing, China; the modified RIFO assay can be a practical tool for rapid detection of RIF resistant and MDR isolates in the routine diagnostic work.     

High S100B Levels Predict Antidepressant Response in Patients With Major Depression Even When Considering Inflammatory and Metabolic Markers

BackgroundThe relationship between antidepressant response and glial, inflammatory, and metabolic markers is poorly understood in depression. This study assessed the ability of biological markers to predict antidepressant response in major depressive disorder (MDD).MethodsWe included 31 MDD outpatients treated with escitalopram or sertraline for 8 consecutive weeks. The Montgomery-Åsberg Depression Rating Scale (MADRS) was administered at baseline and at week 4 and 8 of treatment. Concomitantly, blood samples were collected for the determination of serum S100B, C-reactive protein (CRP), and high-density lipoprotein cholesterol (HDL)-C levels. Treatment response was defined as ≥50% improvement in the MADRS score from baseline to either week 4 or 8. Variables associated with treatment response were included in a linear regression model as predictors of treatment response.ResultsTwenty-seven patients (87%) completed 8 weeks of treatment; 74% and 63% were responders at week 4 and 8, respectively. High S100B and low HDL-C levels at baseline were associated with better treatment response at both time points. Low CRP levels were correlated with better response at week 4. Multivariate analysis showed that high baseline S100B levels and low baseline HDL-C levels were good predictors of treatment response at week 4 (R^2 =0.457, P = .001), while S100B was at week 8 (R² = 0.239, P = .011). Importantly, baseline S100B and HDL-C levels were not associated with depression severity and did not change over time with clinical improvement.ConclusionsSerum S100B levels appear to be a useful biomarker of antidepressant response in MDD even when considering inflammatory and metabolic markers.