MATURITY onset diabetes of the young, GRANULE cells, INSULIN, STEM cells, and INTRACELLULAR calcium
Mutations in HNF1A cause Maturity Onset Diabetes of the Young (HNF1A-MODY). To understand mechanisms of β-cell dysfunction, we generated stem cell-derived pancreatic endocrine cells with hypomorphic mutations in HNF1A. HNF1A-deficient β-cells display impaired basal and glucose stimulated-insulin secretion, reduced intracellular calcium levels in association with a reduction in CACNA1A expression, and accumulation of abnormal insulin granules in association with SYT13 down-regulation. Knockout of CACNA1A and SYT13 reproduce the relevant phenotypes. In HNF1A deficient β-cells, glibenclamide, a sulfonylurea drug used in the treatment of HNF1A-MODY patients, increases intracellular calcium, and restores insulin secretion. While insulin secretion defects are constitutive in β-cells null for HNF1A, β-cells heterozygous for hypomorphic HNF1A (R200Q) mutations lose the ability to secrete insulin gradually; this phenotype is prevented by correction of the mutation. Our studies illuminate the molecular basis for the efficacy of treatment of HNF1A-MODY with sulfonylureas, and suggest promise for the use of cell therapies. hPSCs model of Maturity Onset Diabetes of the Young caused by mutations in the transcription factor HNF1A (HNF1A-MODY), regulates the expression of genes required for the formation of dense-core insulin granules and calcium-dependent insulin secretion, demonstrating a basis to treat HNF1A-MODY patients with sulfonylureas. [ABSTRACT FROM AUTHOR]
Chang, Amy, Chiang, Teresa PY., Kim, Jake D., Mitchell, Jonathan, Alejo, Jennifer L., Jefferis, Alexa A., Avery, Robin K., Tobian, Aaron A. R., Levan, Macey L., Warren, Daniel S., Garonzik‐Wang, Jacqueline M., Massie, Allan B., Segev, Dorry L., and Werbel, William A.
COVID-19 vaccines, TRANSPLANTATION of organs, tissues, etc., VACCINES, and IMMUNE response
Fewer than 45% of solid organ transplant recipients (SOTRs) mount a detectable antispike antibody level after two doses of mRNA SARS-CoV-2 vaccination (D2).1 Various vaccination strategies, including mixing platforms, have been proposed, but there is no consensus on the optimal vaccination sequence to improve immunogenicity.2,3 Although using similar technology, the mRNA-1273 vaccine has been associated with higher peak antibody responses than the use of BNT162b2 in immunosuppressed populations, potentially related to a higher vaccine antigen dose.3,4 We therefore studied whether the use of mRNA-1273 versus BNT162b2 as a third primary vaccine dose (D3) might generate a more robust antibody response in SOTR who remained seronegative after two doses of BNT162b2. Improved humoral immunogenicity with mRNA-1273 versus BNT162b2 as third vaccine dose among solid organ transplant recipients seronegative after two BNT162b2 doses METHODS From our national observational study, approved by the Johns Hopkins Institutional Review Board (IRB00248540),4 we included adult SOTRs who tested seronegative after two doses of BNT162b2 and received either a D3-BNT162b2 or D3-mRNA-1273. [Extracted from the article]
Chang, Amy, Mitchell, Jonathan, Alejo, Jennifer L., Chiang, Teresa P.Y., Abedon, Aura T, Kim, Jake D., Avery, Robin K., Tobian, Aaron A.R., Levan, Macey L., Warren, Daniel S., Garonzik‐Wang, Jacqueline M., Massie, Allan B., Segev, Dorry L., and Werbel, William A.
MOTHERS, PARENT attitudes, SOCIAL norms, AGE distribution, CROSS-sectional method, INTERNET, FATHERS, SEX distribution, PARENTING, ALCOHOL drinking, DESCRIPTIVE statistics, PARENT-child relationships, and PARENTS
Aims This study aimed to examine perceived social norms, the effect of parental drinking on these norms, alcohol use in front of children, and how norms and consumption vary based on child age and gender of the parent. Methods A cross-sectional online panel survey was undertaken with n = 1000 Australian adults (including 670 parents) aged 18–59 years. The survey assessed: alcohol consumption in front of children; normative attitudes towards drinking in the presence of children; and perceived social norms. Results Overall, 33.9% of parents reported drinking a glass of alcohol each day or a couple of times a week, 18.2% reported getting slightly drunk and 7.8% indicated getting visibly drunk each day or a couple of times a week with their children present. In total, 37.5% reported drinking in front of their children at least weekly. Fathers were more likely to drink in front of children than mothers. Most parents deemed drinking small amounts of alcohol in front of children as acceptable but did not accept drunkenness. Respondents were less concerned about a father drinking one or two drinks in front of their children than a mother. Social expectations were not related to child age, but norms related to others' perceived behaviour were. Conclusions Many parents, particularly fathers consume alcohol in front of their children. There is a need to target health promotion strategies to adults and parents consuming in excess of health guidelines, and to the many parents who are consuming alcohol at higher levels in front of their children. [ABSTRACT FROM AUTHOR]
Florvil, Tiffany N., Glover, Kaiama L., Joseph-Gabriel, Annette K., Marino, Katherine M., Mitchell, Robin, Mogoué, Jacqueline-Bethel, and Pinto, Samantha
Signs: Journal of Women in Culture & Society. Summer2022, Vol. 47 Issue 4, p1013-1040. 28p.
BLACK feminism, HISTORY of feminism, FEMINISM, BLACK feminists, WORLD history, CONVERSATION, and RACISM
This roundtable stems from a Zoom event, "New Directions in Feminism and Global Race Studies (a Book Conversation)" with authors Tiffany N. Florvil, Kaiama L. Glover, Annette K. Joseph-Gabriel, Katherine M. Marino, Robin Mitchell, and Jacqueline-Bethel Tchouta Mougoué, hosted by Samantha Pinto. These scholars discussed their recently published books, which expand how we think about transnational feminism and global Black feminisms in the Americas, the Caribbean, Africa, and Europe. The lightly edited transcript of the conversation explores how putting Black women at the center of histories of global feminisms and race studies transforms these fields and the questions that are usually asked. The authors also discussed navigating research challenges and confronting racism in the sources and in the archives. The conversation underscores the importance of intellectual community, as well as the relevance and urgency of Black feminist scholarship today. [ABSTRACT FROM AUTHOR]
Kraatz, Elizabeth, von Spiegel, Jacqueline, Sayers, Robin, and Brady, Anna C.
Theory Into Practice. Jul2022, p1-13. 13p. 1 Chart.
Controversial topics may be uncomfortable for teachers to include in their in-class discussions. However, there are considerable cognitive and social-emotional benefits to engagement in controversial conversations, or classroom discussion about controversial topics. It is critical that teachers support students in respectful discussion to help them develop skills such as problem solving, critical thinking, and the ability to consider issues from multiple perspectives. These skills can enable students to meet larger educational goals such as engaged citizenship. The goal of this article is to highlight the benefits of controversial conversations in the classroom and describe teaching approaches that facilitate effective controversial conversations. First, we identify important factors for teachers’ consideration in supporting effective and beneficial controversial conversations. Second, we provide examples of topics of conversations that may be appropriate for students of varying ages. Third, we review how the structure of conversation, scaffolding, classroom context, relationships, and students’ individual differences can shape controversial conversations. [ABSTRACT FROM AUTHOR]
Dioverti, M Veronica, Gaston, David C, Morris, C Paul, Huff, Carol Ann, Jain, Tania, Jones, Richard, Anders, Viki, Lederman, Howard, Saunders, Jacqueline, Mostafa, Heba H, and Avery, Robin K
Open Forum Infectious Diseases. Jun2022, Vol. 9 Issue 6, p1-5. 5p.
COVID-19, SARS-CoV-2, and REMDESIVIR
Profoundly B-cell-depleted patients can have prolonged severe acute respiratory syndrome coronavirus 2 infections with evidence of active viral replication, due to inability to mount an adequate humoral response to clear the virus. We present 3 B-cell-depleted patients with prolonged coronavirus disease 2019 infection who were successfully treated with a combination of casirivimab/imdevimab and remdesivir. [ABSTRACT FROM AUTHOR]
SOFT robotics, LYMPHEDEMA, SLEEVES, AIR pressure, MICROFLUIDICS, VALVES, MICROFLUIDIC devices, and DRAINAGE
A proof of concept of a novel air microfluidics-enabled soft robotic sleeve to enable lymphedema treatment is presented. Compression sleeves represent the current, suboptimal standard of care, and stationary pumps assist with lymph drainage; however, effective systems that are truly wearable while performing daily activities are very scarce. This problematic trade-off between performance and wearability requires a new solution, which is addressed by an innovative microfluidic device. Its novelty lies in the use of light, small, and inexpensive air microfluidic chips (35 × 20 × 5 mm3 in size) that bring three major advantages compared to their traditional counterparts. First, each chip is designed with 16 fluidic channels with a cross-sectional area varying from 0.04 to 1 mm2, providing sequential inflation and uniform deflation capability to eight air bladders, thereby producing intentional gradient compression to the arm to facilitate lymph fluid circulation. The design is derived from the fundamentals of microfluidics, in particular, hydraulic resistance and paths of least resistance. Second, the air microfluidic chip enables miniaturization of at least eight bulky energy-consuming valves to two miniature solenoid valves for control increasing wearability. Third, the air microfluidic chip has no moving parts, which reduces the noise and energy needed. The cost, simplicity, and scale-up potential of developing methods for making the system are also detailed. The sequential inflation, uniform deflation, and pressure gradient are demonstrated, and the resulted compression and internal air bladder pressure were evaluated. This air microfluidics-enabled sleeve presents tremendous potential toward future improvements in self-care lymphedema management. [ABSTRACT FROM AUTHOR]
Lim, Jacqueline, Pavalagantharajah, Sureka, Verschoor, Chris P, Lentz, Eric, Loeb, Mark, Levine, Mitchell, Smieja, Marek, Mbuagbaw, Lawrence, Kalina, Dale, Tarride, Jean-Eric, O'Shea, Tim, Cvetkovic, Anna, van Gaalen, Sarah, Findlater, Aidan Reid, Lennox, Robin, Bassim, Carol, Lokker, Cynthia, and Alvarez, Elizabeth
PLoS ONE. 4/20/2022, Vol. 17 Issue 4, p1-12. 12p.
COMMUNICABLE diseases, INFECTIOUS arthritis, HOSPITAL patients, CELLULITIS, DRUG abuse, DRUGS, and FISHER exact test
Injection drug use poses a public health challenge. Clinical experience indicates that people who inject drugs (PWID) are hospitalized frequently for infectious diseases, but little is known about outcomes when admitted. Charts were identified from local hospitals between 2013–2018 using consultation lists and hospital record searches. Included individuals injected drugs in the past six months and presented with infection. Charts were accessed using the hospital information system, undergoing primary and secondary reviews using Research Electronic Data Capture (REDCap). The Wilcoxon rank-sum test was used for comparisons between outcome categories. Categorical data were summarized as count and frequency, and compared using Fisher's exact test. Of 240 individuals, 33% were admitted to the intensive care unit, 36% underwent surgery, 12% left against medical advice (AMA), and 9% died. Infectious diagnoses included bacteremia (31%), abscess (29%), endocarditis (29%), cellulitis (20%), sepsis (10%), osteomyelitis (9%), septic arthritis (8%), pneumonia (7%), discitis (2%), meningitis/encephalitis (2%), or other (7%). Sixty-six percent had stable housing and 60% had a family physician. Fifty-four percent of patient-initiated discharges were seen in the emergency department within 30 days and 29% were readmitted. PWID are at risk for infections. Understanding their healthcare trajectory is essential to improve their care. [ABSTRACT FROM AUTHOR]
Chiang, Teresa PY, Alejo, Jennifer L., Mitchell, Jonathan, Kim, Jake D., Abedon, Aura T., Karaba, Andrew H., Thomas, Letitia, Levan, Macey L., Garonzik‐Wang, Jacqueline M., Avery, Robin K., Pekosz, Andrew, Clarke, William A., Warren, Daniel S., Tobian, Aaron A. R., Massie, Allan B., Segev, Dorry L., and Werbel, William A.
American Journal of Transplantation. Apr2022, p1. 7p. 3 Charts.
Heterologous vaccination (“mixing platforms”) for the third (D3) dose of SARS‐CoV‐2 vaccine is a potential strategy to improve antibody responses in solid organ transplant recipients (SOTRs), but data are mixed regarding potential differential immunogenicity. We assessed for differences in immunogenicity and tolerability of homologous (BNT162b2 or mRNA‐1273; D3‐mRNA) versus heterologous (Ad.26.COV2.S; D3‐JJ) D3 among 377 SARS‐CoV‐2‐infection naïve SOTRs who remained seronegative after two mRNA vaccines. We measured anti‐spike titers and used weighted Poisson regression to evaluate seroconversion and development of high‐titers, comparing D3‐JJ to D3‐mRNA, at 1‐, 3‐, and 6 month post‐D3. 1‐month post‐D3, seroconversion (63% vs. 52%, p = .3) and development of high‐titers (29% vs. 25%, p = .7) were comparable between D3‐JJ and D3‐mRNA recipients. 3 month post‐D3, D3‐JJ recipients were 1.4‐fold more likely to seroconvert (80% vs. 57%, weighted incidence‐rate‐ratio: wIRR = 1.101.401.77, p = .006) but not more likely to develop high‐titers (27% vs. 22%, wIRR = 0.440.921.93, p = .8). 6 month post‐D3, D3‐JJ recipients were 1.41‐fold more likely to seroconvert (88% vs. 59%, wIRR = 1.04 1.411.93, p = .029) and 2.63‐fold more likely to develop high‐titers (59% vs. 21%, wIRR = 1.382.635.00, p = .003). There was no differential signal in alloimmune events or reactogenicity between platforms. SOTRs without antibody response after two mRNA vaccines may derive benefit from heterologous Ad.26.COV2.S D3. [ABSTRACT FROM AUTHOR]