Specimen self‐collection and HPV DNA screening in a pilot study of 100,242 women

Since cervical cancer remains common in Mexico despite an established cytology screening program, the Ministry of Health recently introduced pilot front‐line HPV testing into the Mexican cervical cancer screening program (CCSP). Here, we present the key field performance metrics of this population‐based study. High‐risk HPV DNA (hrHPV) testing was conducted on self‐collected vaginal specimens from 100,242 women aged 25–75 years residing in Morelos State. All hrHPV positive women and a random sample of 3.2% (n = 2,864) of hrHPV negative participants were referred for colposcopic examination. The main disease endpoint of interest was cervical intraepithelial neoplasia grade 2 or higher (CIN2+). We calculated relative risk, positive predictive value and negative predictive value adjusted for screening test verification bias. The overall prevalence of hrHPV was 10.8% (95%CI 10.6–11.0). Women positive for hrHPV had a relative risk of 15.7 for histologically detectable CIN2+. The adjusted positive predictive value of the hrHPV test was 2.4% (95%CI 2.1–2.7); whereas the adjusted negative predictive value was 99.8% (95%CI 99.8–99.9). These findings suggest that large‐scale vaginal hrHPV testing in a middle‐income country can identify women at greater risk of advanced cervical abnormalities in a programmatically meaningful way but care is warranted to ensure that disease not detectable at colposcopy is kept to a minimum. PASS shows areas that need improvement and sets the stage for wider use of hrHPV screening of self‐collected vaginal specimens in Mexico.     

Origin of New Lineages by Recombination and Mutation in Avian Infectious Bronchitis Virus from South America

The gammacoronavirus avian infectious bronchitis virus (IBV) is a highly contagious respiratory pathogen of primary economic importance to the global poultry industry. Two IBV lineages (GI-11 and GI-16) have been widely circulating for decades in South America. GI-11 is endemic to South America, and the GI-16 is globally distributed. We obtained full-length IBV genomes from Argentine and Uruguayan farms using Illumina sequencing. Genomes of the GI-11 and GI-16 lineages from Argentina and Uruguay differ in part of the spike coding region. The remaining genome regions are similar to the Chinese and Italian strains of the GI-16 lineage that emerged in Asia or Europe in the 1970s. Our findings support that the indigenous GI-11 strains recombine extensively with the invasive GI-16 strains. During the recombination process, GI-11 acquired most of the sequences of the GI-16, retaining the original S1 sequence. GI-11 strains with recombinant genomes are circulating forms that underwent further local evolution. The current IBV scenario in South America includes the GI-16 lineage, recombinant GI-11 strains sharing high similarity with GI-16 outside S1, and Brazilian GI-11 strains with a divergent genomic background. There is also sporadic recombinant in the GI-11 and GI-16 lineages among vaccine and field strains. Our findings exemplified the ability of IBV to generate emergent lineage by using the S gene in different genomic backgrounds. This unique example of recombinational microevolution underscores the genomic plasticity of IBV in South America.     

Effects of L-Citrulline Supplementation on Endothelial Function and Blood Pressure in Hypertensive Postmenopausal Women

Aging and menopause are associated with decreased nitric oxide bioavailability due to reduced L-arginine (L-ARG) levels contributing to endothelial dysfunction (ED). ED precedes arterial stiffness and hypertension development, a major risk factor for cardiovascular disease. This study investigated the effects of L-citrulline (L-CIT) on endothelial function, aortic stiffness, and resting brachial and aortic blood pressures (BP) in hypertensive postmenopausal women. Twenty-five postmenopausal women were randomized to 4 weeks of L-CIT (10 g) or placebo (PL). Serum L-ARG, brachial artery flow-mediated dilation (FMD), aortic stiffness (carotid-femoral pulse wave velocity, cfPWV), and resting brachial and aortic BP were assessed at 0 and 4 weeks. L-CIT supplementation increased L-ARG levels (Δ13 ± 2 vs. Δ−2 ± 2 µmol/L, p < 0.01) and FMD (Δ1.4 ± 2.0% vs. Δ−0.5 ± 1.7%, p = 0.03) compared to PL. Resting aortic diastolic BP (Δ−2 ± 4 vs. Δ2 ± 5 mmHg, p = 0.01) and mean arterial pressure (Δ−2 ± 4 vs. Δ2 ± 6 mmHg, p = 0.04) were significantly decreased after 4 weeks of L-CIT compared to PL. Although not statistically significant (p = 0.07), cfPWV decreased after L-CIT supplementation by ~0.66 m/s. These findings suggest that L-CIT supplementation improves endothelial function and aortic BP via increased L-ARG availability.     

Synthesis and purification of the aflatoxin B1-lysine adduct

This work reports the chemical synthesis of aflatoxin B₁ (AFB₁)-lysine based on procedures available in the literature, but using lysine without a protection group in the α-amine group. AFB₁-exo-8,9-epoxide was obtained by epoxidation of AFB₁ with chloroperoxybenzoic acid in dichloromethane and phosphate buffer. Purification and identification of the AFB₁-lysine were conducted by liquid chromatography (LC), and its structure was confirmed by LC with mass spectrometer and diode-array detection. The preparation of AFB₁-lysine using lysine without a protection group in the α-amine group was completed in 24?h, being a practical modification of available methods that can be reproduced in analytical laboratories.     

Impact of anticoagulation and antiplatelet therapy on dialysis catheter fibrin sheath formation

PURPOSEFibrin sheaths are a significant cause of dialysis catheter dysfunction. This study aimed to determine the role of anticoagulation, antiplatelet medications, and other factors in delaying fibrin sheath formation.METHODSAn institutional review board-approved retrospective review of all patients treated for tunneled dialysis catheter fibrin sheaths from January 2014 to January 2020 was undertaken. All catheters were symmetric tipped, 14.5 F in diameter, and placed via the internal jugular vein. Seventy patients with venographically confirmed fibrin sheaths that developed after de novo catheter placement were identified. Recurrent fibrin sheaths were excluded. The impact of anticoagulation and antiplatelet therapy, as well as statin therapy, catheter side (right or left), hematocrit, platelet count, prothrombin time (PT), and international normalized ratio (INR), on the time to fibrin sheath formation was determined.RESULTSPatients on anticoagulation had a longer median catheter implantation time of 109.2 days (interquartile range (IQR): 29.3-178.5 days) compared to 80.7 days (IQR: 28.0-168.6 days) among patients not on anticoagulation. Catheter dwell time among patients taking antiplatelet therapy was 86.0 days (IQR: 31.5-160.7 days) versus 74.4 days (IQR: 27.5-202.4 days) for patients not on antiplatelet medication. Patients taking statins versus those not taking statins had median catheter dwell times of 97.5 days (IQR: 27.5-138.5 days) and 62.4 days (IQR: 29.9-259.6 days), respectively. Time to fibrin sheath formation was not significantly associated with hematocrit (P  = .16), platelet count (0.12), PT (P  = .51), or INR (P  = .74).CONCLUSIONAnticoagulation has no significant benefit in delaying sheath formation in patients with tunneled dialysis catheters. Hematologic and coagulation parameters at the time of catheter placement were also not associated with catheter dwell time.

Main points

• Tunneled dialysis catheter dwell time was not significantly longer with anticoagulation, antiplatelet or statin therapy.
• There is no association between baseline coagulation profile and clinically significant fibrin sheath formation.

Tunneled dialysis catheters are frequently the initial access for patients requiring dialysis.^1,2 According to the United States Renal Data System, 80% of end-stage renal disease patients require a catheter when starting dialysis. At 90 days after the start of dialysis, 68.5% of patients are still reliant on catheters.³Fibrin sheaths are a significant cause of catheter dysfunction. Increased catheter infection risk and persistent bacteremia are also associated with fibrin sheaths.⁴ Studies have demonstrated fibrin sheaths can develop within 24 hours of catheter placement and may affect up to 47% of catheters.^5,6 When thrombolytic treatment fails, patients have to undergo additional procedures to exchange the catheter, disrupt the sheath, or strip the sheath, which contribute to patient morbidity.^7-10Prevention of fibrin sheath formation would be expected to have a beneficial impact on satisfactory dialysis maintenance. Placing patients on anticoagulation is a potential strategy that may decrease the risk for catheter dysfunction secondary to fibrin sheaths.¹¹ The aim of this study is to determine whether anticoagulation, antiplatelet medication, or other factors may influence the rate of fibrin sheath development in patients with tunneled dialysis catheters.     

Integration of ER protein quality control mechanisms defines β cell function and ER architecture

Three principal ER quality-control mechanisms, namely, the unfolded protein response, ER-associated degradation (ERAD), and ER-phagy are each important for the maintenance of ER homeostasis, yet how they are integrated to regulate ER homeostasis and organellar architecture in vivo is largely unclear. Here we report intricate crosstalk among the 3 pathways, centered around the SEL1L-HRD1 protein complex of ERAD, in the regulation of organellar organization in β cells. SEL1L-HRD1 ERAD deficiency in β cells triggers activation of autophagy, at least in part, via IRE1α (an endogenous ERAD substrate). In the absence of functional SEL1L-HRD1 ERAD, proinsulin is retained in the ER as high molecular weight conformers, which are subsequently cleared via ER-phagy. A combined loss of both SEL1L and autophagy in β cells leads to diabetes in mice shortly after weaning, with premature death by approximately 11 weeks of age, associated with marked ER retention of proinsulin and β cell loss. Using focused ion beam scanning electron microscopy powered by deep-learning automated image segmentation and 3D reconstruction, our data demonstrate a profound organellar restructuring with a massive expansion of ER volume and network in β cells lacking both SEL1L and autophagy. These data reveal at an unprecedented detail the intimate crosstalk among the 3 ER quality-control mechanisms in the dynamic regulation of organellar architecture and β cell function.     

Dealumination and Characterization of Natural Mordenite-Rich Tuffs

The present study evaluates the feasibility of partially dealuminated natural mordenite as a catalyst support by studying improvement in its textural properties. This is the first study that reports the dealumination of natural zeolite-based tuffs from Ecuador. For this purpose, mordenite-rich tuffs were obtained from deposits close to Guayaquil, Ecuador. The raw material was micronized in order to increase its surface, and treated with NH₄Cl. NH₄⁺ cation-exchanged samples were finally reacted with HCl_(aq) to complete the dealumination process. The partially dealuminated samples were characterized using techniques such as XRD, FT-IR, SEM-EDS, and identification of their textural properties. Dealumination with HCl_(aq) increased the Si/Al ratio up to 9 and kept the crystallographic structure of natural mordenite, as XRD results showed that the structure of mordenite was not altered after the dealumination process. On the other hand, textural properties such as surface area and microporosity were improved as compared to natural mordenite. In view of these results, the feasibility of using natural mordenite as a catalyst support is discussed in this study.