Monoclonal Antibody Production Via Fluidized Bioreactor Technology

Monoclonal antibodies (mAbs) are biologically identical antibodies created by homogenous immune cells originating from the same parent cell. MAbs target a specific epitope of an antigen on a cell’s surface, allowing it to neutralize the antigen. This unique characteristic has made them a key tool in the biopharmaceutical industry for the production of therapeutic drugs. One of these drugs is Rituxan® (rituximab), a mAb drug for the treatment of various cancers and autoimmune diseases. Currently, most mAb products are grown via cell suspension technology in stirred tank bioreactors. However, we have found that by using an integrated bioprocessing model, including conventional cell suspension culture tanks and fluidized bioreactor technology, overall product yield per day is increased by about 7-fold for the production of Rituxan®. Additionally, an economic analysis shows the fluidized bioreactor process is more profitable. Furthermore, though it requires a higher initial investment than the stirred tank process, the differential present worth of the fluidized bioreactor process in comparison to the stirred tank process is $13 billion. Overall, for the production of Rituxan®, the use of fluidized bioreactor technology is a more productive and lucrative process than the conventional stirred tank process

A dominant allele of arabidopsis pectin-binding wall-associated kinase induces a stress response suppressed by MPK6 but not MPK3 mutations

The plant cell wall is composed of a matrix of cellulose fibers, flexible pectin polymers, and an array of assorted carbohydrates and proteins. The receptor-like Wall-Associated Kinases (WAKs) of Arabidopsis bind pectin in the wall, and are necessary both for cell expansion during development and for a response to pathogens and wounding. Mitogen Activated Protein Kinases (MPKs) form a major signaling link between cell surface receptors and both transcriptional and enzyme regulation in eukaryotes, and Arabidopsis MPK6 and MPK3 indeed have important roles in development and the response to stress and pathogens. A dominant allele of WAK2 requires kinase activity and activates a stress response that includes an increased ROS accumulation and the up-regulation of numerous genes involved in pathogen resistance, wounding, and cell wall biogenesis. This dominant allele requires a functional pectin binding and kinase domain, indicating that it is engaged in a WAK signaling pathway. A null mutant of the major plasma membrane ROS-producing enzyme complex, rbohd/f does not suppress the WAK2cTAP-induced phenotype. A mpk6, but not a mpk3, null allele is able to suppress the effects of this dominant WAK2 mutation, thus distinguishing MPK3 and MPK6, whose activity previously was thought to be redundant. Pectin activation of gene expression is abated in a wak2-null, but is tempered by the WAK-dominant allele that induces elevated basal stress-related transcript levels. The results suggest a mechanism in which changes to the cell wall can lead to a large change in cellular responses and help to explain how pathogens and wounding can have general effects on growth. The Author 2011. Published by the Molecular Plant Shanghai Editorial Office in association with Oxford University Press on behalf of CSPB and IPPE, SIBS, CAS.2011 © The Author 2011. Published by the Molecular Plant Shanghai Editorial Office in association with Oxford University Press on behalf of CSPB and IPPE, SIBS, CAS

MFA11 (MFA 2011)

Catalogue of a culminating student exhibition held at the Mildred Lane Kemper Art Museum, May 6-Aug. 1, 2011. Content includes Introduction / Buzz Spector -- Patricia Olynyk -- Marshall N. Klimasewiski -- John Talbott Allen -- Meghan Bean -- Shira Berkowitz / Maggie Stanley Majors -- Darrick Byers, Bryce Olen Robinson -- Jisun Choi -- Zlatko Ćosić -- James R. Daniels -- Kara Daving -- Andrea Degener -- Kristin Fleischmann / Randi Shapiro -- William Frank / Lawrence Ypil -- Nicholas Kania -- Katherine McCullough -- Jordan McGirk / Aditi Machado -- Zachary Miller -- Esther Murphy / Maggie Stanley Majors -- Kathryn Neale -- Christopher Ottinger / Melissa Olson -- Maia Palmer -- Nicole Petrescu / Melissa Olson -- Lauren Pressler / Randi Shapiro -- Whitney Sage / Aliya A. Reich -- Donna Smith.https://openscholarship.wustl.edu/books/1005/thumbnail.jp

Randomized trial of achieving healthy lifestyles in psychiatric rehabilitation: the ACHIEVE trial

<p>Abstract</p> <p>Background</p> <p>Overweight and obesity are highly prevalent among persons with serious mental illness. These conditions likely contribute to premature cardiovascular disease and a 20 to 30 percent shortened life expectancy in this vulnerable population. Persons with serious mental illness need effective, appropriately tailored behavioral interventions to achieve and maintain weight loss. Psychiatric rehabilitation day programs provide logical intervention settings because mental health consumers often attend regularly and exercise can take place on-site. This paper describes the Randomized Trial of Achieving Healthy Lifestyles in Psychiatric Rehabilitation (ACHIEVE). The goal of the study is to determine the effectiveness of a behavioral weight loss intervention among persons with serious mental illness that attend psychiatric rehabilitation programs. Participants randomized to the intervention arm of the study are hypothesized to have greater weight loss than the control group.</p> <p>Methods/Design</p> <p>A targeted 320 men and women with serious mental illness and overweight or obesity (body mass index ≥ 25.0 kg/m²) will be recruited from 10 psychiatric rehabilitation programs across Maryland. The core design is a randomized, two-arm, parallel, multi-site clinical trial to compare the effectiveness of an 18-month behavioral weight loss intervention to usual care. Active intervention participants receive weight management sessions and physical activity classes on-site led by study interventionists. The intervention incorporates cognitive adaptations for persons with serious mental illness attending psychiatric rehabilitation programs. The initial intensive intervention period is six months, followed by a twelve-month maintenance period in which trained rehabilitation program staff assume responsibility for delivering parts of the intervention. Primary outcomes are weight loss at six and 18 months.</p> <p>Discussion</p> <p>Evidence-based approaches to the high burden of obesity and cardiovascular disease risk in person with serious mental illness are urgently needed. The ACHIEVE Trial is tailored to persons with serious mental illness in community settings. This multi-site randomized clinical trial will provide a rigorous evaluation of a practical behavioral intervention designed to accomplish and sustain weight loss in persons with serious mental illness.</p> <p>Trial Registration</p> <p>Clinical Trials.gov NCT00902694</p

Effects of Red-Cell Storage Duration on Patients Undergoing Cardiac Surgery

Some observational studies have reported that transfusion of red-cell units that have been stored for more than 2 to 3 weeks is associated with serious, even fatal, adverse events. Patients undergoingcardiac surgery may be especially vulnerable to the adverse effects of transfusion

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

Glomangioma of Uncertain Malignant Potential: A Case Report

Glomus tumors are rare benign tumors which commonly affect the hand but are seldom seen extradigitally. Less commonly seen is the glomangioma, a variant of benign glomus tumor, and even rarer is the glomangiosarcoma, a malignant variant. Determining malignancy can be difficult and an intermediate diagnosis, glomus tumor of uncertain malignant potential, has been proposed. We present a case of a 56-year-old male with a recurrent forearm mass diagnosed as a glomangioma of uncertain malignant potential. Although the characteristics and behavior of malignant cases are still incompletely understood, it is important that a high index of suspicion be maintained when approaching these tumors, especially when large or recurrent. Glomangiomas should be included in the differential diagnosis when evaluating soft tissue masses in the forearm and should be evaluated for malignant features

Session 6: Economic Development, Revitalization, and Entrepreneurship

Moderator: Meghan McCullough. University of Mississippi, Center for Population Studies Intelligent Communities: Transitioning to the Digital Age / Roberto Gallardo. Mississippi State University Extension Service, Intelligent Community Institute With the digital age in full-swing and the digital divide becoming a real threat to community and economic development, the ability of communities to understand the challenges of the digital age is critical. A four module outreach program piloted by the Mississippi State University Extension Service helps rural communities transition to, plan for, and prosper in the digital age. The ultimate objective is to build inclusive and sustainable communities. A six-indicator framework developed by the worldwide Intelligent Community Forum is used to guide communities through this transition. Revitalizing Manufacturing in the Delta / Frank Hull. University of Mississippi and the Cass Business School (London) This paper profiles opportunities for growing jobs in the Delta by the propagation of principles for manufacturing excellence. Two decades ago, a survey of manufacturers in the MS Delta sponsored by MSU documented many excellent enterprises. Six of these manufacturers joined a forum to share and disseminate best practices in the region. This paper codifies best practices for manufacturing excellence and recommends strategies and tactics for expanding existing manufacturers and attracting new ones. The principles employed by these leading manufacturers are consistent with established sociological theories that are confirmed by case studies of each of the establishments. Each of the organizations built collaboration among diverse employees to achieve high levels of performance. The resulting solidarity blurred status distinctions based on race, gender, and ethnicity resulting in relatively high levels of social solidarity. This solidarity helped these manufacturers achieve high levels of productivity in specific measurable ways and innovate in ways large and small. Success stories are highlighted to illustrate winning practices that can help the Delta attract manufacturing jobs as the US economy continues to re-shore work that was sometimes recklessly outsourced to external nations. The Delta has succeeded in the past and can do so again. The Quapaw Canoe Company Success Story / John Ruskey. Quapaw Canoe Company This is an introduction to starting an outdoor recreation mission-oriented business in the Mississippi Delta. The presentation features a slide show focusing on real life lessons learned at Quapaw Canoe Company, est 1998, in Clarksdale, MS, with outpost bases in Helena, AR and Natchez, MS. Topics include dreaming your business, vision, mission statement, objectives, strategy, business models, and others appropriate to subject

A 5-Year Review of the Designated Leadership Positions of the American Society for Surgery of the Hand (ASSH)

Purpose: Despite near equal representation of women in medical schools since 2008, the percentage of women in surgical subspecialties has remained low. Hand surgery accounts for one of the highest percentages of women, at 19%. Ascension to leadership positions has not yet been fully studied among this group. Our study examined whether increased female representation translated to representation at different levels within the organization. Methods: The 2014 to 2018 membership rosters were obtained from the American Society for Surgery of the Hand (ASSH) and compared by gender. Leadership and volunteer committee positions were evaluated as published in the annual ASSH Committee Reference Book. Leadership positions were defined as appointment to committee chair or Council or acceptance to the Young Leaders Program. Rates of engagement were compared for each of the leadership activities. When available, the time for advancement through various leadership positions was also analyzed by gender. Results: Between 2014 and 2018, the percentage of female ASSH Active Members steadily increased from 11% to 14%. Engagement in early career activities such as committees and the Young Leaders Program also increased: committee positions from 16% to 17% and Young Leaders Program membership from 27% to 40% female representation across the same period. Relative to the overall number of eligible females in the society, women applied at a greater rate and achieved positions at an average of 2 years earlier than their male counterparts. Conclusions: There is a steady increase in the percentage of women within the ASSH. Female ASSH members applied for early career leadership positions at a higher rate and achieved these positions earlier than their male counterparts. This may indicate that future women leaders are appropriately supported in the organization. Clinical relevance: The ASSH has been committed to increasing gender and ethnic diversity. Early analysis demonstrates an increase in women surgeons’ participation in early career leadership activities within the society