Multivalent interaction and selectivities in selectin binding of functionalized gold colloids decorated with carbohydrate mimetics

Colloidal gold particles with functionalized organic shells were applied as novel selectin binders. The ligand shell was terminated with different monocyclic carbohydrate mimetics as simplified analogs of the sLe(x) unit found in biological selectin ligands. The multivalent presentation of the sulfated selectin binding epitopes on the gold particles led to extremely high binding affinities towards L- and P-selectin and IC(50) values in the subnanomolar range. Depending on the ring size of the sulfated carbohydrate mimetic, its substitution pattern and its configuration, different selectivities for either L-selectin or P-selectin were obtained. These selectivities were not found for gold particles with simple acyclic sulfated alcohols, diols and triols in the ligand shell. In addition, the influence of the particle size and the thickness of the hydrophobic organic shell were systematically investigated

An exploration of the impact of celebrity on the HIV/AIDS pandemic

The framework we present in this article separates into three generations the celebrity/personality involvement in the AIDS movement that has been steadily building momentum over the past 25 years. We analyze the celebrification of HIV/AIDS and the role of the media in the process. We contend the relationship between celebrity, the public and HIV/AIDS is multipurpose: celebrities maintain a positive public presence between projects while allowing themselves and their supporting fans to feel good about taking on and affecting a meaningful cause. Celebrities are vehicles and embodiments of concern that act as proxies for their various audiences. And this is their power–celebrities are embodiments of their audiences. The awareness that celebrities have brought to the HIV/AIDS epidemic has resulted in better treatment for victims and increased government support for medical research, and yet has also distracted the public’s attention from the scope of the epidemic. It is the third generation of celebrities who are refocusing efforts on worldwide prevention and a cure for HIV/AIDS

Alteration of Lung Physiology with the Administration of Convalescent Plasma in ARDS Patients Intubated with COVID-19 Pneumonia

**Background:** It remains unknown to what degree lung physiology is altered by administration of convalescent plasma in patients intubated with ARDS due to COVID-19 pneumonia. Although no longer clinically used as treatment for COVID-19, convalescent plasma therapy could be deployed again should new virus threats emerge in the future. **Aim:** To evaluate changes in ventilator physiologic variables in response to convalescent plasma transfusion using a retrospective, observational, case control study of intubated patients with COVID-19 pneumonia. **Methods:** Patients who were receiving mechanical ventilation due to COVID-19 at the time of administration of convalescent plasma therapy (CPT) were matched to control patients who did not receive convalescent plasma. Ventilatory data such as compliance, positive end-expiratory pressure (PEEP), FiO~2~ administered, PaO~2~/FiO~2~ ratio, and tidal volume were collected pre and post administration. Panel-level random-effects linear regression models were used to assess the mean difference and interactions between CPT and cases vs controls over time. **Results:** 12 patients received CPT while intubated and were matched to 35 intubated control patients who did not receive CPT. In total, 857 separate measurements of static compliance were obtained over time. No significant difference in static compliance was seen after CPT. In cases, adjusted mean static compliance was 30.8 (95% CI (23.3, 38.4))mL/cm H~2~O before CPT and 28.2 (95% CI (20.7,35.6)) mL/cm H~2~O afterwards. Controls adjusted mean static compliance was 33.9 (95% CI (29.5, 38.4)) mL/cm H~2~O before versus 32.2 (95% CI (27.9, 36.5)) mL/cm H~2~O afterwards. Variables that had small but statistically significant differences pre vs post CPT among cases and controls were systolic and diastolic blood pressure, FiO~2~, heart rate, applied PEEP, and respiratory rate. **Conclusion:** While some statistically significant physiologic effects were seen with CPT in mechanically ventilated patients, these were deemed to be small and clinically insignificant. This is consistent with prior research on less acutely ill COVID-19 patients

The eyeless mouse mutation (ey1) removes an alternative start codon from the Rx/rax homeobox gene

Summary: The eyeless inbred mouse strain ZRDCT has long served as a spontaneous model for human anophthalmia and the evolutionary reduction of eyes that has occurred in some naturally blind mammals. ZRDCT mice have orbits but lack eyes and optic tracts and have hypothalamic abnormalities. Segregation data suggest that a small number of interacting genes are responsible, including at least one major recessive locus, ey1 . Although predicted since the 1940s, these loci were never identified. We mapped ey1 to chromosome 18 using an F2 genome scan and there found a Met10→Leu mutation in Rx/rax , a homeobox gene that is expressed in the anterior headfold, developing retina, pineal, and hypothalamus and is translated via a leaky scanning mechanism. The mutation affects a conserved AUG codon that functions as an alternative translation initiation site and consequently reduces the abundance of Rx protein. In contrast to a targeted Rx null allele, which causes anophthalmia, central nervous system defects, and neonatal death, the hypomorphic M10L allele is fully viable. genesis 31:43–53, 2001. © 2001 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/35266/1/10003_ftp.pd

Stimulated monocyte IL-6 secretion predicts survival of patients with head and neck squamous cell carcinoma

<p>Abstract</p> <p>Background</p> <p>This study was performed in order to determine whether monocyte <it>in vitro </it>function is associated with presence, stage and prognosis of head and neck squamous cell carcinoma (HNSCC) disease.</p> <p>Methods</p> <p>Prospective study describing outcome, after at least five years observation, of patients treated for HNSCC disease in relation to their monocyte function. Sixty-five patients with newly diagnosed HNSCC and eighteen control patients were studied. Monocyte responsiveness was assessed by measuring levels of monocyte <it>in vitro </it>interleukin (IL)-6 and monocyte chemotactic peptide (MCP)-1 secretion after 24 hours of endotoxin stimulation in cultures supplied either with 20% autologous serum (AS) or serum free medium (SFM). Survival, and if relevant, cause of death, was determined at least 5 years following primary diagnosis.</p> <p>Results</p> <p>All patients, as a group, had higher <it>in vitro </it>monocyte responsiveness in terms of IL-6 (AS) (<it>t </it>= 2.03; <it>p </it>< 0.05) and MCP-1 (SFM) (<it>t </it>= 2.49; <it>p </it>< 0.05) compared to controls. Increased <it>in vitro </it>monocyte IL-6 endotoxin responsiveness under the SFM condition was associated with decreased survival rate (Hazard ratio (HR) = 2.27; Confidence interval (CI) = 1.05–4.88; <it>p </it>< 0.05). The predictive value of monocyte responsiveness, as measured by IL-6, was also retained when adjusted for age, gender and disease stage of patients (HR = 2.67; CI = 1.03–6.92; <it>p </it>< 0.05). With respect to MCP-1, low endotoxin-stimulated responsiveness (AS), analysed by Kaplan-Meier method, predicted decreased survival (χ = 4.0; <it>p </it>< 0.05).</p> <p>Conclusion</p> <p>In HNSCC patients, changed monocyte <it>in vitro </it>response to endotoxin, as measured by increased IL-6 (SFM) and decreased MCP-1 (AS) responsiveness, are negative prognostic factors.</p

Aortic valve infective endocarditis due to Streptococcus pyogenes : A case report

Group A Streptococcus is a common cause of pharyngitis, scarlet fever, glomerulonephritis, and various skin infections. However, there have only been a few reports of Group A Streptococcus (GAS) associated with infective endocarditis. We present a case of a 31-year-old male who presented to the hospital with a few days of weakness and myalgias after recently receiving treatment with azithromycin for GAS pharyngitis as an outpatient. The patient was admitted to the intensive care unit in septic shock from Group A beta-hemolytic Streptococcus bacteremia and acute hypoxic respiratory failure. He was found to have new severe aortic insufficiency from infective endocarditis. He underwent urgent partial aortic valve annuloplasty reconstruction and incision and drainage of root abscess with intraoperative cultures growing gram positive cocci consistent with GAS. The majority of cases of infective endocarditis are caused by Staphylococcus aureus, virdians group Streptococci and Streptococcus gallolyticus, while Streptococcus pneumoniae and Streptococcus pyogenes have the lowest prevalence of infective endocarditis. Penicillin remains the first line treatment for GAS pharyngitis. However, in cases of severe penicillin allergy, macrolides should be avoided given the increasing rate of macrolide resistance GAS strains. This case emphasizes the importance of using beta-lactams as first line therapy for GAS pharyngitis to avoid harmful complications and infection recurrence