Effect of pH and ions on the electronic structure of saccharin

The sodium salt of saccharin is biologically more active as a urothelial cell mitogen in vivo, when fed to male rats, than are the potassium or calcium salts or the acid form, despite similar concentrations of saccharin excreted in the urine. The differences in bladder-mitogenic activity between sodium saccharin and the other salts of saccharin may be the result of known differences in the ionic composition of the urine of rats receiving these various forms of saccharin. These changes in the rat urine following administration of the different salts of saccharin could be responsible for the observed mitogenic responses to oral saccharin; alternatively the differences in the ionic composition of the urine could result in changes in the electronic structure of the saccharin molecule itself, allowing it to be more active in certain ionic environments. Since the pKa of saccharin is 1.8, essentially all of the saccharin in urine (pH greater than 5) will exist in the ionized form. We have used 17O, 15N, 13C and two-dimensional nuclear magnetic resonance (NMR) spectroscopy to explore the electronic structure of the saccharin molecule in aqueous solution. By observing the NMR spectra of the saccharinate ion in the presence of varying concentrations of hydrogen, potassium, sodium, calcium, magnesium, bicarbonate and urate, we have demonstrated that at physiological levels none of these ions significantly alters the electronic structure of the saccharin molecule. Hence the differences in the mitogenic response to the different saccharin salts cannot be explained by alterations in the structure of the saccharin molecule.     

Human papillomavirus infection and cervical disease in human immunodeficiency virus-1-infected women

OBJECTIVE: To report on the natural history of high-risk human papillomavirus (HPV) infection and cervical disease in human immunodeficiency virus (HIV)-1-infected women living in Cape Town, South Africa. METHODS: This was a prospective study of 400 untreated, HIV-1-infected women who underwent high-risk HPV DNA testing, cytology, colposcopy, histology, and CD4 count testing every 6 months for 36 months. Human immunodeficiency virus viral loads and HPV type distribution were determined at entry and after 18 months. RESULTS: Sixty-eight percent of the women were high-risk HPV DNA positive at entry, 35% had a cytologic diagnosis of low-grade squamous intraepithelial lesion (LSIL), and 13% had high-grade squamous intraepithelial lesion (HSIL). There were no cancers. Abnormal cytology and high-risk HPV positivity were strongly correlated with low CD4 counts and high HIV viral loads. The most prevalent types of HPV were HPV-16, -52, -53, -35, and -18. Incident high-risk HPV infection occurred in 22%, and of those infected with high-risk HPV, 94% of infections persisted over an 18-month period, and 6% cleared their infections. Cytologic progression to SIL from normal/atypical squamous cells of undetermined significance cytology occurred in 17% of cases, but only 4% of cases of LSIL progressed to HSIL. CONCLUSION: There is a high level of high-risk HPV infection in HIV-1 infected women, but progression to HSIL over 36 months occurred in the minority of cases. We recommend an initial colposcopy for an abnormal test, and if no high-grade lesion is identified, triennial screening would be appropriate. Human papillomavirus type 16 was the commonest, and HPV-18 was the fifth commonest, suggesting that vaccination against these two types would have a significant effect. LEVEL OF EVIDENCE: II.     

Evaluation of a Wastewater-Based Epidemiological Approach to Estimate the Prevalence of SARS-CoV-2 Infections and the Detection of Viral Variants in Disparate Oregon Communities at City and Neighborhood Scales

Background: Positive correlations have been reported between wastewater SARS-CoV-2 concentrations and a community’s burden of infection, disease or both. However, previous studies mostly compared wastewater to clinical case counts or nonrepresentative convenience samples, limiting their quantitative potential.Objectives: This study examined whether wastewater SARS-CoV-2 concentrations could provide better estimations for SARS-CoV-2 community prevalence than reported cases of COVID-19. In addition, this study tested whether wastewater-based epidemiology methods could identify neighborhood-level COVID-19 hotspots and SARS-CoV-2 variants.Methods: Community SARS-CoV-2 prevalence was estimated from eight randomized door-to-door nasal swab sampling events in six Oregon communities of disparate size, location, and demography over a 10-month period. Simultaneously, wastewater SARS-CoV-2 concentrations were quantified at each community’s wastewater treatment plant and from 22 Newport, Oregon, neighborhoods. SARS-CoV-2 RNA was sequenced from all positive wastewater and nasal swab samples. Clinically reported case counts were obtained from the Oregon Health Authority.Results: Estimated community SARS-CoV-2 prevalence ranged from 8 to 1,687/10,000 persons. Community wastewater SARS-CoV-2 concentrations ranged from 2.9 to 5.1log10 gene copies per liter. Wastewater SARS-CoV-2 concentrations were more highly correlated (Pearson’s r=0.96; R2=0.91) with community prevalence than were clinically reported cases of COVID-19 (Pearson’s r=0.85; R2=0.73). Monte Carlo simulations indicated that wastewater SARS-CoV-2 concentrations were significantly better than clinically reported cases at estimating prevalence (p<0.05). In addition, wastewater analyses determined neighborhood-level COVID-19 hot spots and identified SARS-CoV-2 variants (B.1 and B.1.399) at the neighborhood and city scales.Discussion: The greater reliability of wastewater SARS-CoV-2 concentrations over clinically reported case counts was likely due to systematic biases that affect reported case counts, including variations in access to testing and underreporting of asymptomatic cases. With these advantages, combined with scalability and low costs, wastewater-based epidemiology can be a key component in public health surveillance of COVID-19 and other communicable infections. https://doi.org/10.1289/{"type":"entrez-protein","attrs":{"text":"EHP10289","term_id":"372009674","term_text":"EHP10289"}}EHP10289     

Recovery of T cell subsets after autologous bone marrow transplantation is mainly due to proliferation of mature T cells in the graft

In 22 patients with malignancies, treated with high-dose chemoradiotherapy and autologous bone marrow transplantation (BMT), peripheral blood T cell subsets and functions were studied. In ten cytomegalovirus (CMV)-negative patients, CD4+ and CD8+ T cells (representing T cells of the helper/inducer phenotype and T cells of the suppressor/cytotoxic phenotype, respectively), recovered slowly and simultaneously. In 12 CMV-positive patients, however, CD8+ T cells recovered more rapidly than CD4+ T cells and rose to increased counts. No T cells with an immature phenotype (CD1+, OKT6+) were observed. Lymphocyte stimulation by herpes simplex virus infected fibroblasts (and by CMV-infected fibroblasts in CMV-positive patients) in contrast remained high and even increased after BMT in both groups. These data indicate that T cell recovery after autologous BMT is mainly due to proliferation of mature T cells present in the BM graft and not to generation of new T cells from T cell precursors.     

Successful intra-arterial thrombolytic therapy for a right middle cerebral artery stroke in a 2-year-old supported by a ventricular assist device

Embolic stroke is a common complication in patients on ventricular assist devices in both adults and children. The reported incidence of strokes in children supported by VAD's varies from 7 to 38%. The rapid increase in recent years in the availability of both adult and pediatric VADs will likely add to the overall prevalence of strokes in patients being bridged to heart transplant. Strokes in this population can be lethal as they frequently necessitate withdrawal of the extracorporeal device support and withdrawal from the organ transplant waiting list. We present a case of a fully anti-coagulated 29-month-old supported on a Berlin EXCOR LVAD (Berlin, Germany) with embolic stroke which was treated successfully with direct thrombolysis with recombinant tissue plasminogen activator. This is the first report which uses intra-arterial thrombolytics while on a ventricular assist device in a pediatric patient.     

Reproducibility of the cervical range of motion (CROM) device for individuals with sub-acute whiplash associated disorders

Purpose  

The objective of this study was to evaluate the reproducibility of the cervical range of motion device when measuring both active and passive range of motion in a group of individuals with sub-acute Whiplash Associated Disorders (WAD).     

Unresolved priapism secondary to tamsulosin

Tamsulosin is the most potent adrenergic alpha-1 antagonist used for the treatment of benign prostatic hyperplasia. Priapism has been reported rarely in patients taking Prazosin, Doxazosin and Terazosin. We describe an otherwise healthy man with recurrent and then persistent unresolved priapism after the use of tamsulosin. Initial treatment consisted of aspiration and intracavernosal irrigation of iced saline and vasoconstrictive agent, but in vain. We then performed Winters procedure but that too failed and the priapism persisted. Health-care professionals should inform all patients taking such medications about rare but possible serious adverse effects.