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

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

Functional Analysis of Hsp70 Inhibitors

<div><p>The molecular chaperones of the Hsp70 family have been recognized as targets for anti-cancer therapy. Since several paralogs of Hsp70 proteins exist in cytosol, endoplasmic reticulum and mitochondria, we investigated which isoform needs to be down-regulated for reducing viability of cancer cells. For two recently identified small molecule inhibitors, VER-155008 and 2-phenylethynesulfonamide (PES), which are proposed to target different sites in Hsp70s, we analyzed the molecular mode of action in vitro. We found that for significant reduction of viability of cancer cells simultaneous knockdown of heat-inducible Hsp70 (HSPA1) and constitutive Hsc70 (HSPA8) is necessary. The compound VER-155008, which binds to the nucleotide binding site of Hsp70, arrests the nucleotide binding domain (NBD) in a half-open conformation and thereby acts as ATP-competitive inhibitor that prevents allosteric control between NBD and substrate binding domain (SBD). Compound PES interacts with the SBD of Hsp70 in an unspecific, detergent-like fashion, under the conditions tested. None of the two inhibitors investigated was isoform-specific.</p></div