Mutations in the 23S rRNA gene are associated with clarithromycin resistance in Helicobacter pylori isolates in Brazil

BACKGROUND: Resistance of Helicobacter pylori to clarithromycin has been associated with A2142G and A2143G point mutations in the 23S rRNA gene. Thus, the purpose of the present study was to determine the prevalence of each mutation in 52 clarithromycin-resistant H. pylori strains and to characterize the influence each type of mutation on the MIC. METHODS: The MIC for clarithromycin was determined by the agar dilution method, and the point mutations of H. pylori were detected by PCR followed by restriction fragment length polymorphism. RESULTS: Clarithromycin MICs ranged from 2 to >256 microgram ml(-1 )among the 52 strains included in this study. Both the A2142G and the A2143G mutations were present in 94.2% of clarithromycin-resistant H. pylori strains examined. A relationship was observed between the presence of the A2142G mutation and the highest MIC values (p = 0.01). CONCLUSION: In an H. pylori-infected population, the A2142G mutation may incur to a greater probability of treatment failure if clarithromycin is used

Preclinical Efficacy of Cabazitaxel Loaded Poly (2-alkyl cyanoacrylate) Nanoparticle Variants

\ua9 2024 Valsalakumari et al. This work is published and licensed by Dove Medical Press Limited.Background: Biodegradable poly(alkyl cyanoacrylate) (PACA) nanoparticles (NPs) are receiving increasing attention in anti-cancer nanomedicine development not only for targeted cancer chemotherapy, but also for modulation of the tumor microenvironment. We previously reported promising results with cabazitaxel (CBZ) loaded poly(2-ethylbutyl cyanoacrylate) NPs (PEBCA-CBZ NPs) in a patient derived xenograft (PDX) model of triple-negative breast cancer, and this was associated with a decrease in M2 macrophages. The present study aims at comparing two endotoxin-free PACA NP variants (PEBCA and poly(2-ethylhexyl cyanoacrylate); PEHCA), loaded with CBZ and test whether conjugation with folate would improve their effect. Methods: Cytotoxicity assays and cellular uptake of NPs by flow cytometry were performed in different breast cancer cells. Biodistribution and efficacy studies were performed in PDX models of breast cancer. Tumor associated immune cells were analyzed by multiparametric flow cytometry. Results: In vitro studies showed similar NP-induced cytotoxicity patterns despite difference in early NP internalization. On intravenous injection, the liver cleared the majority of NPs. Efficacy studies in the HBCx39 PDX model demonstrated an enhanced effect of drug-loaded PEBCA variants compared with free drug and PEHCA NPs. Furthermore, the folate conjugated PEBCA variant did not show any enhanced effects compared with the unconjugated counterpart which might be due to unfavorable orientation of folate on the NPs. Finally, analyses of the immune cell populations in tumors revealed that treatment with drug loaded PEBCA variants affected the myeloid cells, especially macrophages, contributing to an inflammatory, immune activated tumor microenvironment. Conclusion: We report for the first time, comparative efficacy of PEBCA and PEHCA NP variants in triple negative breast cancer models and show that CBZ-loaded PEBCA NPs exhibit a combined effect on tumor cells and on the tumor associated myeloid compartment, which may boost the anti-tumor response

Gate-tunable black phosphorus spin valve with nanosecond spin lifetimes

Two-dimensional materials offer new opportunities for both fundamental science and technological applications, by exploiting the electron spin. While graphene is very promising for spin communication due to its extraordinary electron mobility, the lack of a band gap restricts its prospects for semiconducting spin devices such as spin diodes and bipolar spin transistors. The recent emergence of 2D semiconductors could help overcome this basic challenge. In this letter we report the first important step towards making 2D semiconductor spin devices. We have fabricated a spin valve based on ultra-thin (5 nm) semiconducting black phosphorus (bP), and established fundamental spin properties of this spin channel material which supports all electrical spin injection, transport, precession and detection up to room temperature (RT). Inserting a few layers of boron nitride between the ferromagnetic electrodes and bP alleviates the notorious conductivity mismatch problem and allows efficient electrical spin injection into an n-type bP. In the non-local spin valve geometry we measure Hanle spin precession and observe spin relaxation times as high as 4 ns, with spin relaxation lengths exceeding 6 um. Our experimental results are in a very good agreement with first-principles calculations and demonstrate that Elliott-Yafet spin relaxation mechanism is dominant. We also demonstrate that spin transport in ultra-thin bP depends strongly on the charge carrier concentration, and can be manipulated by the electric field effect

Hyaluronidase of Bloodsucking Insects and Its Enhancing Effect on Leishmania Infection in Mice

Hyaluronidases are enzymes degrading the extracellular matrix of vertebrates. Bloodsucking insects use them to cleave the skin of the host, enlarge the feeding lesion and acquire the blood meal. In addition, resulting fragments of extracellular matrix modulate local immune response of the host, which may positively affect transmission of vector-borne diseases, including leishmaniasis. Leishmaniases are diseases with a wide spectrum of clinical forms, from a relatively mild cutaneous affection to life-threatening visceral disease. Their causative agents, protozoans of the genus Leishmania, are transmitted by phlebotomine sand flies. Sand fly saliva was described to enhance Leishmania infection, but the information about molecules responsible for this exacerbating effect is still very limited. In the present work we demonstrated hyaluronidase activity in salivary glands of various Diptera and in fleas. In addition, we showed that hyaluronidase exacerbates Leishmania lesions in mice and propose that salivary hyaluronidase may facilitate the spread of other vector-borne microorganisms

Anatomical and procedural features associated with aortic root rupture during balloon-expandable transcatheter aortic valve replacement

Aortic root rupture is a major concern with balloon-expandable transcatheter aortic valve replacement (TAVR). We sought to identify predictors of aortic root rupture during balloon-expandable TAVR by using multidetector computed tomography

Precise measurement of the W-boson mass with the CDF II detector

We have measured the W-boson mass MW using data corresponding to 2.2/fb of integrated luminosity collected in proton-antiproton collisions at 1.96 TeV with the CDF II detector at the Fermilab Tevatron collider. Samples consisting of 470126 W->enu candidates and 624708 W->munu candidates yield the measurement MW = 80387 +- 12 (stat) +- 15 (syst) = 80387 +- 19 MeV. This is the most precise measurement of the W-boson mass to date and significantly exceeds the precision of all previous measurements combined