Demographic and clinical characteristics associated with glomerular filtration rates in living kidney donors

Due to the shortage of organs, living donor acceptance criteria are becoming less stringent. An accurate determination of the glomerular filtration rate (GFR) is critical in the evaluation of living kidney donors and a value exceeding 80 ml/min per 1.73 m2 is usually considered suitable. To improve strategies for kidney donor screening, an understanding of factors that affect GFR is needed. Here we studied the relationships between donor GFR measured by 125I-iothalamate clearances (mGFR) and age, gender, race, and decade of care in living kidney donors evaluated at the Cleveland Clinic from 1972 to 2005. We report the normal reference ranges for 1057 prospective donors (56% female, 11% African American). Females had slightly higher mGFR than males after adjustment for body surface area, but there were no differences due to race. The lower limit of normal for donors (5th percentile) was less than 80 ml/min per 1.73 m2 for females over age 45 and for males over age 40. We found a significant doubling in the rate of GFR decline in donors over age 45 as compared to younger donors. The age of the donors and body mass index increased over time, but their mGFR, adjusted for body surface area, significantly declined by 1.49±0.61 ml/min per 1.73 m2 per decade of testing. Our study shows that age and gender are important factors determining normal GFR in living kidney donors

Reptilian Heart Development And The Molecular Basis Of Cardiac Chamber Evolution

The emergence of terrestrial life witnessed the need for more sophisticated circulatory systems. This has evolved in birds, mammals and crocodilians into complete septation of the heart into left and right sides, allowing separate pulmonary and systemic circulatory systems, a key requirement for the evolution of endothermy(1-3). However, the evolution of the amniote heart is poorly understood. Reptilian hearts have been the subject of debate in the context of the evolution of cardiac septation: do they possess a single ventricular chamber or two incompletely septated ventricles(4-7)? Here we examine heart development in the red-eared slider turtle, Trachemys scripta elegans (a chelonian), and the green anole, Anolis carolinensis (a squamate), focusing on gene expression in the developing ventricles. Both reptiles initially form a ventricular chamber that homogenously expresses the T-box transcription factor gene Tbx5. In contrast, in birds and mammals, Tbx5 is restricted to left ventricle precursors(8,9). In later stages, Tbx5 expression in the turtle (but not anole) heart is gradually restricted to a distinct left ventricle, forming a left-right gradient. This suggests that Tbx5 expression was refined during evolution to pattern the ventricles. In support of this hypothesis, we show that loss of Tbx5 in the mouse ventricle results in a single chamber lacking distinct identity, indicating a requirement for Tbx5 in septation. Importantly, misexpression of Tbx5 throughout the developing myocardium to mimic the reptilian expression pattern also results in a single mispatterned ventricular chamber lacking septation. Thus ventricular septation is established by a steep and correctly positioned Tbx5 gradient. Our findings provide a molecular mechanism for the evolution of the amniote ventricle, and support the concept that altered expression of developmental regulators is a key mechanism of vertebrate evolution

Antibody-Directed Effector Cell Therapy of Tumors: Analysis and Optimization Using a Physiologically Based Pharmacokinetic Model

The failure of the cellular immune response to stop solid tumor growth has been the subject of much research. Although the mechanisms for tumor evasion of immune response are poorly understood, one viable explanation is that tumor-killing lymphocytes cannot reach the tumor cells in sufficient quantity to keep the tumor in check. Recently, the use of bifunctional antibodies (BFAs) has been proposed as a way to direct immune cells to the tumor: one arm of the antibody is specific for a known tumor-associated antigen and the other for a lymphocyte marker such as CD3. Injecting this BFA should presumably result in cross-linking of lymphocytes (either endogenous or adoptively transferred) with tumor cells, thereby enhancing therapy. Results from such an approach, however, are often disappointing — frequently there is no benefit gained by using the BFA. We have analyzed the retargeting of endogenous effector cells by BFA using a physiologically based whole-body pharmacokinetic model that accounts for interactions between all relevant species in the various organs and tumor. Our results suggest that the design of the BFA is critical and the binding constants of the antigen and lymphocyte binding epitopes need to be optimized for successful therapy

Education in the Anthropocene: assessing planetary health science standards in the USA

The environmental crises defining the Anthropocene demand ubiquitous mitigation efforts, met with collective support. Yet, disengagement and disbelief surrounding planetary health threats are pervasive, especially in the USA. This scepticism may be influenced by inadequate education addressing the scope and urgency of the planetary health crisis. We analysed current K-12 science standards related to planetary health throughout the USA, assessing their quality and potential predictors of variation. While planetary health education varies widely across the USA with respect to the presence and depth of terms, most science standards neglected to convey these concepts with a sense of urgency. Furthermore, state/territory dominant political party and primary gross domestic product (GDP) contributor were each predictive of the quality of planetary health education. We propose that a nation-wide science standard could fully address the urgency of the planetary health crisis and prevent political bias from influencing the breadth and depth of concepts covered.Open access articleThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

[Conocimiento básico asociado al fatalismo generado por el COVID-19 en estudiantes de medicina de Bolivia]

El objetivo fue determinar si el conocimiento básico está asociado al fatalismo que fue generado por el COVID-19 en estudiantes de medicina de Bolivia. Estudio transversal analítico, generado a través de una encuesta virtual, con escalas validadas para medir el conocimiento y el fatalismo ante la posibilidad de enfermarse por COVID-19, esto en 4 facultades de medicina de Bolivia. Se obtuvo resultados descriptivos y analíticos de dicha asociación, ajustado por otras variables. En el análisis multivariado se encontró que hubo un mayor nivel de conocimiento conforme aumentaba el año académico (3er año p=0,012, 4to año p=0,031, 5to año p=0,001 y el internado p=0,013; todos a comparación del 1er año), en cambio, hubo más conocimiento entre los estudiantes que fueron menos fatalistas (RPa: 0,76; IC95%: 0,68-0,85%; valor p<0,001) y entre los que estudiaban en algunas universidades (UNIFRANZ p<0,001 y UNITEPC p<0,001, ambas a comparación de la UMSS); ajustados por el sexo y la edad de los encuestados. En conclusión, el que los estudiantes hayan tenido percepciones fatalistas se asoció de forma inversa al conocimiento que tuvieron respecto a la enfermedad; además, hubo asociación según el año de estudios y la universidad donde estudiaba

An Emerging Population: Kidney Transplant Candidates Who Are Placed on the Waiting List after Liver, Heart, and Lung Transplantation

Background and objectives: ESRD has an adverse impact on patients who have had previous nonrenal solid-organ transplants (NRTxs; liver, heart, lung) and may be referred for a kidney transplant (KTx)