Spatial displacement sensitivity of X- and Y-cells in the dorsal lateral geniculate nucleus of the cat

The sensitivity of X- and Y-cells in the dorsal lateral geniculate nucleus of the cat to small, temporally modulated displacements of grating stimuli was measured at 0.175, 0.25, 0.50, 1.00, and 2.00 c/deg. For every cell, two threshold measures were determined: first, a contrast threshold with a counterphase grating and then a displacement threshold with a grating matched in spatial frequency, but whose contrast was 2.5 times the threshold value. The results showed that displacement thresholds of both X- and Y-cells decreased with increasing spatial frequency. At low spatial frequencies, mean displacement thresholds of X- and Y-cells were similar, but at intermediate spatial frequencies, Y-cell thresholds were lower than X. X-cell displacement thresholds were lower than Y only at the highest spatial frequency tested. Consistent with previous reports, contrast thresholds also varied with spatial frequency for both X- and Y-cells. The local luminance differences produced by the contrast threshold and displacement threshold stimuli for the two classes of cells were compared. Across all spatial frequencies, the change in position of the gratings at displacement threshold produced smaller luminance differences than the counterphase gratings at contrast threshold. This enhanced sensitivity of X- and Y-cells to a local luminance changes produced by grating displacement was related to the high spatial contrast of the grating and not to the displacement per se.     

The Wisconsin Epidemiologic Study of Diabetic Retinopathy. VII. Diabetic nonproliferative retinal lesions

The prevalences of hard exudates, soft exudates, intraretinal microvascular abnormalities (IRMAs), and venous beading and their relationships to demographic and other characteristics were examined in a population-based study in southern Wisconsin. For participants whose age at diagnosis was less than 30 years and who were taking insulin (N = 996), hard exudates were found in 24.2%, soft exudates in 15.3%, IRMAs in 16.5%, and venous beading in 7.0% of the population. For participants whose age at diagnosis was 30 years or older and who were taking insulin (N = 674), hard exudates were found in 28.3%, soft exudates in 15.5%, IRMAs in 8.8%, and venous beading in 3.2%. For older-onset persons not taking insulin (N = 696), hard exudates were found in 9.4%, soft exudates in 5.4%, IRMAs in 2.6%, and venous beading in 0.9% of the population. The severities of the lesions were found to be consistently associated with longer duration of diabetes in younger-onset persons and the presence of proteinuria in older-onset persons.     

Sputum changes associated with therapy for endobronchial exacerbation in cystic fibrosis

We sought to define objective indicators of the resolution of Pseudomonas aeruginosa endobronchial infection in patients with cystic fibrosis. We prospectively studied 75 patients admitted for treatment of a pulmonary exacerbation and quantitated sputum bacterial density, DNA content, and the concentration of albumin and total protein in sputum, and compared these values with clinical evaluation. Eleven of the 75 patients had systemic signs, fever, and leukocytosis, which we arbitrarily defined as due to endobronchial infection. At the end of hospitalization, these 11 patients were afebrile, had peripheral leukocyte counts in the normal range, and were judged improved. Sputum P. aeruginosa density, DNA content, and total protein content on admission were similar in the two illness groups. Hospitalization and parenteral antibiotic administration for an average of 14.6 days were associated with improved pulmonary function in all 75 subjects (P values for forced vital capacity, forced expiratory volume at 1 second, and peak expiratory flow rate were all less than 0.001). With improvement, there was a decrease in sputum P. aeruginosa density (mean of both groups decreased from 10(7.80) CFU/g on admission to 10(5.96) CFU/g; P less than 0.001), and a decreased DNA concentration (overall mean 4.73 +/- 4.75 on admission to 2.76 +/- 2.49 mg/g; P less than 0.002). The decrease in sputum total protein concentration for both groups was not significant (overall mean 60.5 +/- 48.4 to 43.9 +/- 38.2 mg/g; P = 0.06). Sputum albumin concentrations did not change in either group. We conclude that in cystic fibrosis subjects with a pulmonary exacerbation, bacterial density, sputum DNA and protein content decrease with hospitalization and parenteral antibiotic therapy. At the end of treatment, these indices of sputum infection and inflammation correlate with improved pulmonary function and clinical improvement. These changes are independent of the presence or absence of fever on admission.     

Gender differences in sexual and injection risk behavior among active young injection drug users in San Francisco (the UFO study)

Female injection drug users (IDUs) represent a large proportion of persons infected with HIV in the United States, and women who inject drugs have a high incidence of hepatitis B virus (HBV) and hepatitis C virus (HCV) injection. Therefore, it is important to understand the role of gender in injection risk behavior and the transmission of blood-borne virus. In 2000–2002, 844 young (<30 years old) IDUs were surveyed in San Francisco. We compared self-reported risk behavior between 584 males and 260 female participants from cross-sectional baseline data. We used logistic regression to determine whether demographic, structural, and relationship variables explained increased needle borrowing, drug preparation equipment sharing, and being injected by another IDU among females compared to males. Females were significantly younger than males and were more likely to engage in needle borrowing, ancillary equipment sharing, and being injected by someone else. Females were more likely than males to report recent sexual intercourse and to have IDU sex partners. Females and males were not different with respect to education, race/ethnicity, or housing status. In logistic regression models for borrowing a used needle and sharing drug preparation equipment, increased risk in females was explained by having an injection partner who was also a sexual partner. Injecting risk was greater in the young female compared to male IDUs despite equivalent frequency of injecting. Overlapping sexual and injection partnerships were a key factor in explaining increased injection risk in females. Females were more likely to be injected by another IDU even after adjusting for years injecting, being in a relationship with another IDU, and other potential confounders. Interventions to reduce sexual and injection practices that put women at risk of contracting hepatitis and HIV are needed.     

COVID-19 therapeutics: Challenges and directions for the future

The emergence of SARS-CoV-2 triggering the COVID-19 pandemic ranks as arguably the greatest medical emergency of the last century. COVID-19 has highlighted health disparities both within and between countries and will leave a lasting impact on global society. Nonetheless, substantial investment in life sciences over recent decades has facilitated a rapid scientific response with innovations in viral characterization, testing, and sequencing. Perhaps most remarkably, this permitted the development of highly effective vaccines, which are being distributed globally at unprecedented speed. In contrast, drug treatments for the established disease have delivered limited benefits so far. Innovative and rapid approaches in the design and execution of large-scale clinical trials and repurposing of existing drugs have saved many lives; however, many more remain at risk. In this review we describe challenges and unmet needs, discuss existing therapeutics, and address future opportunities. Consideration is given to factors that have hindered drug development in order to support planning for the next pandemic challenge and to allow rapid and cost-effective development of new therapeutics with equitable delivery.     

Ethylcholine mustard aziridinium ion (AF64A) impairs cholinergic neuromuscular transmission in the guinea-pig ileum and urinary bladder, and cholinergic neuromodulation in the enteric nervous system of the guinea-pig distal colon

AF64A was examined for its ability to impair cholinergic neurotransmission in the autonomic nervous system. In the guinea-pig ileum AF64A impaired cholinergic neuromuscular transmission. In the guinea-pig urinary bladder AF64A selectivity impaired the cholinergic but not the purinergic component of neuromuscular transmission. In the guinea-pig colon circular muscle AF64A impaired cholinergic neuromodulation of the inhibitory transmission but not the inhibitory transmission itself. The nature of impairment of cholinergic transmission by AF64A is discussed.