Production of Inactivated Influenza H5N1 Vaccines from MDCK Cells in Serum-Free Medium

BACKGROUND: Highly pathogenic influenza viruses pose a constant threat which could lead to a global pandemic. Vaccination remains the principal measure to reduce morbidity and mortality from such pandemics. The availability and surging demand for pandemic vaccines needs to be addressed in the preparedness plans. This study presents an improved high-yield manufacturing process for the inactivated influenza H5N1 vaccines using Madin-Darby canine kidney (MDCK) cells grown in a serum-free (SF) medium microcarrier cell culture system. PRINCIPAL FINDING: The current study has evaluated the performance of cell adaptation switched from serum-containing (SC) medium to several commercial SF media. The selected SF medium was further evaluated in various bioreactor culture systems for process scale-up evaluation. No significant difference was found in the cell growth in different sizes of bioreactors studied. In the 7.5 L bioreactor runs, the cell concentration reached to 2.3 × 10(6) cells/mL after 5 days. The maximum virus titers of 1024 Hemagglutinin (HA) units/50 µL and 7.1 ± 0.3 × 10(8) pfu/mL were obtained after 3 days infection. The concentration of HA antigen as determined by SRID was found to be 14.1 µg/mL which was higher than those obtained from the SC medium. A mouse immunogenicity study showed that the formalin-inactivated purified SF vaccine candidate formulated with alum adjuvant could induce protective level of virus neutralization titers similar to those obtained from the SC medium. In addition, the H5N1 viruses produced from either SC or SF media showed the same antigenic reactivity with the NIBRG14 standard antisera. CONCLUSIONS: The advantages of this SF cell-based manufacturing process could reduce the animal serum contamination, the cost and lot-to-lot variation of SC medium production. This study provides useful information to manufacturers that are planning to use SF medium for cell-based influenza vaccine production

Cesarean and Vbac Rates Among Immigrant vs. Native-Born Women: A Retrospective Observational Study From Taiwan Cesarean Delivery and Vbac Among Immigrant Women in Taiwan

Background Cultural and ethnic roots impact women\u27s fertility and delivery preferences This study investigated whether the likelihood of cesarean delivery, primary cesarean, and vaginal delivery after cesarean (VBAC) varies by maternal national origin. Methods We conducted a nation-wide, population-based, observational study using secondary data from Taiwan. De-identified data were obtained on all 392,246 singleton live births (≥500 g; ≥20 weeks) born to native-born Taiwanese, Vietnamese and mainland Chinese-born mothers between January 1 2006 and December 31 2007 from Taiwan\u27s nation-wide birth certificate data. Our analytic samples consisted of the following: for overall cesarean likelihood 392,246 births, primary cesarean 336,766 (excluding repeat cesarean and VBAC), and VBAC 55,480 births (excluding primary cesarean and vaginal births without previous cesarean). Our main outcome measures were the odds of cesarean delivery, primary cesarean delivery and VBAC for Vietnamese and Chinese immigrant mothers relative to Taiwanese mothers, using multiple regression analyses to adjust for maternal and neonatal characteristics, paternal age, institutional setting, and major obstetric complications. Results Unadjusted overall cesarean, primary cesarean, and VBAC rates were 33.9%, 23.0% and 4.0% for Taiwanese, 27.6%, 20.1% and 5.0% for mainland Chinese, and 19.3%, 13.9 and 6.1% for Vietnamese respectively. Adjusted for confounders, Vietnamese mothers were less likely than native-born Taiwanese to have overall and primary cesarean delivery (OR = 0.59 and 0.58 respectively), followed by Chinese mothers (both ORs = 0.90 relative to native-born Taiwanese). Vietnamese mothers were most likely to have successful VBAC (OR = 1.58), followed by Chinese mothers (OR = 1.25). Conclusion Immigrant Vietnamese and Chinese mothers have lower odds of cesarean and higher VBAC odds than native-born Taiwanese, consistent with lower cesarean rates prevailing in their home countries (Vietnam 10.1%; mainland China 20% - 50% rural and urban respectively)

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

The effects of bi-functional anti-adhesion scaffolds on flexor tendon healing in a rabbit model

10.1002/jbm.b.3407710672605-261

Decreases in smoking prevalence in Asian communities served by the Racial and Ethnic Approaches to Community Health (REACH) project.

ObjectivesWe examined trends in smoking prevalence from 2002 through 2006 in 4 Asian communities served by the Racial and Ethnic Approaches to Community Health (REACH) intervention.MethodsAnnual survey data from 2002 through 2006 were gathered in 4 REACH Asian communities. Trends in the age-standardized prevalence of current smoking for men in 2 Vietnamese communities, 1 Cambodian community, and 1 Asian American/Pacific Islander (API) community were examined and compared with nationwide US and state-specific data from the Behavioral Risk Factor Surveillance System.ResultsPrevalence of current smoking decreased dramatically among men in REACH communities. The reduction rate was significantly greater than that observed in the general US or API male population, and it was greater than reduction rates observed in the states in which REACH communities were located. There was little change in the quit ratio of men at the state and national levels, but there was a significant increase in quit ratios in the REACH communities, indicating increases in the proportions of smokers who had quit smoking.ConclusionsSmoking prevalence decreased in Asian communities served by the REACH project, and these decreases were larger than nationwide decreases in smoking prevalence observed for the same period. However, disparities in smoking prevalence remain a concern among Cambodian men and non-English-speaking Vietnamese men; these subgroups continue to smoke at a higher rate than do men nationwide