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Abstract Based upon clinical observations and recent reports, we anticipated there would be an inverse dose–response relationship between the severe acute respiratory syndrome‐coronavirus 2 (SARS‐CoV‐2) viral load and the time‐to‐positivity after application of the nasal swab sample in two popular home coronavirus disease 2019 (COVID‐19) antigen tests, BinaxNOW COVID‐19 Antigen Self‐Test and Flowflex COVID‐19 Antigen Home Test, both of which are sensitive to the nucleocapsid protein (NP). The relationship among the concentration of NP, WA1, and Omicron XBB.1.5 viral strains and the time‐to‐positive result by visual assessment in the tests was examined. The correlation between reverse transcription‐polymerase chain reaction cycle threshold (Ct) values and time‐to‐positivity in clinical samples (training set) also was determined. Strong inverse correlations were obtained between the concentration of the NP, WA1, XBB.1.5, Ct values for dilutions of both WA1 and XBB.1.5, as well as Ct values from the clinical samples and time‐to‐positivity in both antigen tests. The correlation between the actual and predicted Ct values interpolated from the training set was high with both tests in a second set of clinical samples. These results, together with those of other investigations with similar tests, suggest that the time‐to‐positive visual result in most, if not all, lateral flow COVID‐19 antigen tests can be utilized to estimate SARS‐CoV‐2 viral concentrations.

Abstract Background The advent of direct-acting antivirals (DAAs)—a form of hepatitis C (HCV) treatment associated with shorter treatment course and greater efficacy—offers an unprecedented opportunity to eliminate HCV, but only if care delivery systems are developed to extend treatment to people who inject drugs (PWID). To support the design of a community-pharmacy program, we explored perspectives of PWID with chronic HCV with regard to barriers, motivators, preferences, and prior experiences related to HCV treatment and pharmacists. Methods We conducted semi-structured interviews with people living with HCV who reported active injection drug use. Participants were recruited from local community service and clinical organizations in the Seattle, Washington region, and focus groups and interviews were conducted in-person or via phone/video-conference. Rapid Assessment Process was used to analyze qualitative data. Dual coders used structured templates to summarize findings and engaged in iterative review to identify themes. Results Among the 40 participants, 65% were male, 52.5% were white, and 80% were not stably housed. On average, participants had been injecting drugs for 14 years and living with HCV for 6 years. Analyses revealed 3 themes: (1) limited knowledge regarding HCV and DAA treatments; (2) barriers/motivators for receiving treatment included fear of side effects, prior stigmatizing behaviors from physicians, and desire to protect relatives and the PWID community from HCV transmission; and (3) preferences for HCV care delivery, including a need for person-centered, low-barrier, and collaborative treatment integrated with other care (e.g. primary care and addiction treatment) for PWID. Participants were generally receptive to a community-pharmacy model for HCV treatment, but prior interactions with pharmacists were mixed and there were some concerns expressed that care delivered by pharmacists would not be equivalent to that of physicians. Conclusions Even in the direct-acting antivirals era, people who inject drugs still face major barriers to hepatitis C treatment which may be reduced by providing low-barrier points of access for care through pharmacists. Key recommendations for community-pharmacy design included providing care team training to reduce stigma and ensuring care team structures and culture target PWID-specific needs for education and engagement.

Diabetes mellitus may cause severe damage to retinal blood vessels. The central aim of this study was to test the hypothesis that sulodexide, a mixture of glycosaminoglycans, has a protective effect against hyperglycemia-induced endothelial dysfunction in the retina. Functional studies were performed in isolated porcine retinal arterioles. Vessels were cannulated and incubated with highly concentrated glucose solution (HG, 25 mM D-glucose) +/− sulodexide (50/5/0.5 μg/mL) or normally concentrated glucose solution (NG, 5.5 mM D-glucose) +/− sulodexide for two hours. Endothelium-dependent and endothelium-independent vasodilatation were measured by videomicroscopy. Reactive oxygen species (ROS) were quantified by dihydroethidium (DHE) fluorescence. Using high-pressure liquid chromatography (HPLC), the intrinsic antioxidant properties of sulodexide were investigated. Quantitative PCR was used to determine mRNA expression of regulatory, inflammatory, and redox genes in retinal arterioles, some of which were subsequently quantified at the protein level by immunofluorescence microscopy. Incubation of retinal arterioles with HG caused significant impairment of endothelium-dependent vasodilation, whereas endothelium-independent responses were not affected. In the HG group, ROS formation was markedly increased in the vascular wall. Strikingly, sulodexide had a protective effect against hyperglycemia-induced ROS formation in the vascular wall and had a concentration-dependent protective effect against endothelial dysfunction. Although sulodexide itself had only negligible antioxidant properties, it prevented hyperglycemia-induced overexpression of the pro-oxidant redox enzymes, NOX4 and NOX5. The data of the present study provide evidence that sulodexide has a protective effect against hyperglycemia-induced oxidative stress and endothelial dysfunction in porcine retinal arterioles, possibly by modulation of redox enzyme expression.

Soft robotics is an expanding area with multiple applications; however, building low-cost, soft, and flexible robots requires the development of sensors that can be directly integrated into the soft robotics fabrication process. Thus, the motivation for this work was the design of a low-cost fabrication process of flexible sensors that can detect touch and deformation. The fabrication process proposed uses a flexible polymer nanocomposite with permanent magnets strategically placed where the conductive electrodes should be. The nanocomposite is based on poly(dimethylsiloxane) (PDMS) and multi-walled carbon nanotubes (MWCNTs). The MWCNT contains ferromagnetic impurities remaining from the synthesis process, which can be used for magnetic manipulation. Several electrode geometries were successfully simulated and tested. The magnetic patterning was simulated, allowing the fabrication of conductive patterns within the composite. This fabrication process allowed the reduction of the electrical resistivity of the nanocomposites as compared to the composites with homogeneous MWCNT dispersion. It also allowed the fabrication of piezoresistive and triboelectric sensors at MWCNT concentration as low as 0.5 wt.%. The fabrication process proposed is flexible, allows the development of sensors for soft robotics, as well as monitoring large and unconventional areas, and may be adapted to different mould shapes and polymers at low cost.

Hot embossing is a small-scale, low-cost processing technology that can deliver products to the market in a short time. This microreplication technology is well established to produce polymeric components and has applications in several industrial sectors. The use of micropowder hot embossing in the production of metal components is an emerging and challenging process that, when compared to other typical technologies, brings some economic advantages in a volatile market with an increasing tendency to manufacture customized products. The main objective of this review is to analyze the potential of powder hot embossing and its developments in the production of metallic microparts/components. This technology requires four distinct steps: (1) production feedstock (preparation of mixtures), (2) hot embossing (shape forming), (3) debinding and (4) sintering. These steps are interrelated and influence the characteristics of the final metallic microparts. This study summarizes the approaches implemented for the use of different metallic powders and polymeric binder systems for the preparation of the feedstock, the mold materials and the critical conditions tested in the embossing step to produce green parts, and the production of the final parts through the application of debinding and sintering. Powder hot embossing is a viable replication technology that allows the production of new metallic microcomponents, contributing to the global scientific effort of miniaturizing manufacturing process, equipment and products. The merit of powder hot embossing for industrialization needs further development to assert itself in the market and compete with other micromanufacturing techniques.

Latently infecting viruses are an important class of virus that plays a key role in viral evolution and human health. Here we report a genome-scale forward-genetics screen for host-dependencies of the latently-infecting bacteriophage lambda. This screen identified 57 Escherichia coli (E. coli) genes--over half of which have not been previously associated with infection--that when knocked out inhibited lambda phage's ability to replicate. Our results demonstrate a highly integrated network between lambda and its host, in striking contrast to the results from a similar screen using the lytic-only infecting T7 virus. We then measured the growth of E. coli under normal and infected conditions, using wild-type and knockout strains deficient in one of the identified host genes, and found that genes from the same pathway often exhibited similar growth dynamics. This observation, combined with further computational and experimental analysis, led us to identify a previously unannotated gene, yneJ, as a novel regulator of lamB gene expression. A surprising result of this work was the identification of two highly conserved pathways involved in tRNA thiolation-one pathway is required for efficient lambda replication, while the other has anti-viral properties inhibiting lambda replication. Based on our data, it appears that 2-thiouridine modification of tRNAGlu, tRNAGln, and tRNALys is particularly important for the efficient production of infectious lambda phage particles.

We have analyzed the survival motor neuron gene (SMN1) dosage in 100 parents of children with homozygous SMN1 deletions. Of these parents, 96 (96%) demonstrated the expected one-copy SMN1 carrier genotype. However, four parents (4%) were observed to have a normal two-copy SMN1 dosage. The presence of two intact SMN1 genes in the parent of an affected child indicates either the occurrence of a de novo mutation event or a situation in which one chromosome has two copies of SMN1, whereas the other is null. We have separated individual chromosomes from two of these parents with two-copy SMN1 dosage by somatic cell hybridization and have employed a modified quantitative dosage assay to provide direct evidence that one parent is a two-copy/zero-copy SMN1 carrier, whereas the other parent had an affected child as the result of a de novo mutation. These findings are important for assessing the recurrence risk of parents of children with spinal muscular atrophy and for providing accurate family counseling. [ABSTRACT FROM AUTHOR]

No abstract available for this article. [ABSTRACT FROM PUBLISHER]