Ex vivo normothermic perfusion (EVNP) is a novel method of preservation that restores circulation and allows an organ to regain function prior to transplantation. The aim of this study was to assess ...the effects of EVNP in kidneys from marginal donors. Eighteen kidneys from extended criteria donors (ECD) underwent a period of EVNP immediately before transplantation. Kidneys were perfused with a plasma free red‐cell based solution at a mean temperature of 34.6°C. The outcome of these kidneys was compared to a control group of 47 ECD kidneys that underwent static cold storage (CS). The mean donor age was 61 ± 1 years in the EVNP and 62 ± 6 years in the CS group (p = 0.520). EVNP kidneys were perfused for an average of 63 ± 16 min and all were transplanted successfully. The delayed graft function rate (DGF), defined as the requirement for dialysis within the first 7 days was 1/18 patients (5.6%) in the EVNP group versus 17/47 (36.2%) in the CS group (p = 0.014). There was no difference in graft or patient survival at 12 months (p = 0.510, 1.000). This first series of EVNP in renal transplantation demonstrates that this technique is both feasible and safe. Our preliminary data suggests that EVNP offers promise as a new technique of kidney preservation.
This study reports early promising results from a pilot experience with ex vivo normothermic kidney perfusion using extended criteria donor kidneys.
•Starch fine structures were measured by size-exclusion chromatography.•Amylopectin chain-length distribution was fitted in a biosynthesis model.•Hardness and stickiness of cooked rice grains were ...tested by texture analyzer.•Statistical correlation found between structural characteristics and rice texture.
Statistically and causally meaningful relationships are established between starch molecular structure (the molecular distribution of branched starch and the chain length distribution of debranched starch) and texture (hardness and stickiness) of cooked rice grains. The amounts of amylose chains with degree of polymerization (DP) 100–20,000, and of long amylopectin chains, positively correlated with hardness, while amylopectin chains with DP<70 and amylose molecular size both showed negative correlations with hardness (p<0.05). There was also a significant negative correlation between stickiness and the amounts of long amylopectin chains (p<0.01). For rices with similar amylose content, the amount of amylose chains with DP 1000–2000 positively correlated with hardness while size negatively correlated with hardness (p<0.05). This indicates for the first time that, regardless of amylose content, rice varieties with smaller amylose molecular sizes and with higher proportions of long amylose chains have a harder texture after cooking.
Frontotemporal lobar degeneration is a neurodegenerative disorder affecting over 50,000 people in the United States alone. The most common pathological subtype of FTLD is the presence of ...ubiquitinated TAR DNA binding protein 43 (TDP-43) accumulations in frontal and temporal brain regions at autopsy. While some cases of FTLD-TDP can be attributed to the inheritance of disease-causing mutations, the majority of cases arise with no known genetic cause. In 2010, the first genome-wide association study was conducted in patients with FTLD-TDP to determine potential genetic risk factors for this homogenous subgroup of dementia patients, leading to the identification of the
TMEM106B
locus on chromosome 7. In this manuscript, we review the initial discovery and replication studies describing
TMEM106B
variants as disease risk factors and modifiers in TDP-43 proteinopathies, such as FTLD-TDP caused by progranulin (
GRN
) or chromosome 9 open reading frame 72 (
C9orf72
) mutations, as well as Alzheimer’s disease and hippocampal sclerosis. We further summarize what is currently known about the previously uncharacterized TMEM106B protein and its role as a potential regulator of lysosomal function, and we discuss how modifying TMEM106B levels might uncover promising therapeutic strategies for individuals suffering from TDP-43 proteinopathy.
Several families have been reported with autosomal-dominant frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS), genetically linked to chromosome 9p21. Here, we report an expansion ...of a noncoding GGGGCC hexanucleotide repeat in the gene C9ORF72 that is strongly associated with disease in a large FTD/ALS kindred, previously reported to be conclusively linked to chromosome 9p. This same repeat expansion was identified in the majority of our families with a combined FTD/ALS phenotype and TDP-43-based pathology. Analysis of extended clinical series found the C9ORF72 repeat expansion to be the most common genetic abnormality in both familial FTD (11.7%) and familial ALS (23.5%). The repeat expansion leads to the loss of one alternatively spliced C9ORF72 transcript and to formation of nuclear RNA foci, suggesting multiple disease mechanisms. Our findings indicate that repeat expansion in C9ORF72 is a major cause of both FTD and ALS.
► Noncoding repeat expansion in C9ORF72 causes FTD and ALS linked to chromosome 9p ► C9ORF72 repeat expansion forms nuclear RNA foci in brain and spinal cord ► Repeat expansion results in loss of one alternatively spliced C9ORF72 transcript ► Repeat expansion in C9ORF72 is a major cause of both FTD and ALS
Abstract
Many classrooms in higher education still rely on a transformative approach to teaching where students attend lectures and earn course grades through examination. In the modern age, ...traditional lectures are argued by some as obsolete and do not address the learning needs of today's students. An emerging pedagogical approach is the concept of the flipped classroom. The flipped classroom can simply be described as students viewing asynchronous video lectures on their own and then engaging in active learning during scheduled class times. In this study, we examined the flipped classroom teaching environment on student learning gains in an Introduction to Equine Science course. Students (n = 130) were asked to view 7.5 h of recorded lectures divided into 8 learning modules, take online quizzes to enforce lecture viewing, take 3 in-class exams, and prepare to participate in active learning during scheduled class times. Active learning approaches included individual activities, paired activities, informal small groups, and large group activities. When compared to students in the traditional lecture format in earlier years, students in the flipped format scored higher on all 3 exams (P < 0.05), with both formats taught by the same instructor. Analysis of ACT scores demonstrated no intellectual capacity differences between the student populations. To evaluate any gains in critical thinking, flipped format students were asked to take the Cornell Critical Thinking Exam (version X). Scores improved from the pretest (50.8 ± 0.57) to the posttest (54.4 ± 0.58; P < 0.01). In the flipped course, no correlations were found with student performance and interactions with online content. Students were asked in class to evaluate their experiences based on a 5-point Likert scale: 1 (strongly disagree) to 5 (strongly agree). The flipped classroom was ranked as an enjoyable learning experience with a mean of 4.4 ± 0.10, while students responded positively to other pointed questions. In formal course evaluations, flipped format students ranked the following higher (P < 0.05): instructor availability to assist students; encouragement of independent, creative, and critical thinking; and amount learned. Overall, the flipped classroom proved to be a positive learning experience for students. As the classroom continues to modernize, pedagogical approaches such as the flipped classroom should be considered for many lecture-style courses taught in the animal sciences.
The elementary excitations of vibration in solids are phonons. But in liquids phonons are extremely short lived and marginalized. In this Letter through classical and ab initio molecular dynamics ...simulations of the liquid state of various metallic systems we show that different excitations, the local configurational excitations in the atomic connectivity network, are the elementary excitations in high temperature metallic liquids. We also demonstrate that the competition between the configurational excitations and phonons determines the so-called crossover phenomenon in liquids. These discoveries open the way to the explanation of various complex phenomena in liquids, such as fragility and the rapid increase in viscosity toward the glass transition, in terms of these excitations.
The rapid cell turnover of the intestinal epithelium is achieved from small numbers of stem cells located in the base of glandular crypts. These stem cells have been variously described as rapidly ...cycling or quiescent. A functional arrangement of stem cells that reconciles both of these behaviours has so far been difficult to obtain. Alternative explanations for quiescent cells have been that they act as a parallel or reserve population that replace rapidly cycling stem cells periodically or after injury; their exact nature remains unknown. Here we show mouse intestinal quiescent cells to be precursors that are committed to mature into differentiated secretory cells of the Paneth and enteroendocrine lineage. However, crucially we find that after intestinal injury they are capable of extensive proliferation and can give rise to clones comprising the main epithelial cell types. Thus, quiescent cells can be recalled to the stem-cell state. These findings establish quiescent cells as an effective clonogenic reserve and provide a motivation for investigating their role in pathologies such as colorectal cancers and intestinal inflammation.
Lineage-tracing approaches, widely used to characterize stem cell populations, rely on the specificity and stability of individual markers for accurate results. We present a method in which genetic ...labeling in the intestinal epithelium is acquired as a mutation-induced clonal mark during DNA replication. By determining the rate of mutation in vivo and combining this data with the known neutral-drift dynamics that describe intestinal stem cell replacement, we quantify the number of functional stem cells in crypts and adenomas. Contrary to previous reports, we find that significantly lower numbers of “working” stem cells are present in the intestinal epithelium (five to seven per crypt) and in adenomas (nine per gland), and that those stem cells are also replaced at a significantly lower rate. These findings suggest that the bulk of tumor stem cell divisions serve only to replace stem cell loss, with rare clonal victors driving gland repopulation and tumor growth.
•Replication-dependent clonal label applied to infer stem cell dynamics•Stem cell numbers and replacement rates are lower than previous estimates•Stem cell dynamics are unchanging with age•Low stem cell numbers but high replacement rates follow oncogenic transformation
A replication-dependent clonal-label approach reveals significantly lower than expected numbers of “working” stem cells in the intestinal epithelium and in adenomas and slower rates of stem cell replacement.
Background
A significant proportion of donation after circulatory death (DCD) kidneys are declined for transplantation because of concerns over their quality. Ex vivo normothermic machine perfusion ...(NMP) provides a unique opportunity to assess the quality of a kidney and determine its suitability for transplantation.
Methods
In phase 1 of this study, declined human DCD kidneys underwent NMP assessment for 60 min. Kidneys were graded 1–5 using a quality assessment score (QAS) based on macroscopic perfusion, renal blood flow and urine output during NMP. In phase 2 of the study, declined DCD kidneys were assessed by NMP with an intention to transplant them.
Results
In phase 1, 18 of 42 DCD kidneys were declined owing to poor in situ perfusion. After NMP, 28 kidneys had a QAS of 1–3, and were considered suitable for transplantation. In phase 2, ten of 55 declined DCD kidneys underwent assessment by NMP. Eight kidneys had been declined because of poor in situ flushing in the donor and five of these were transplanted successfully. Four of the five kidneys had initial graft function.
Conclusion
NMP technology can be used to increase the number of DCD kidney transplants by assessing their quality before transplantation.
Increases available kidneys
The transtheoretical model and the stages of change are often used to adapt treatment to the individual client. The aims of this study were to review the stages of change and popular measures of ...change readiness in psychotherapy and to conduct a meta‐analysis of the relation between readiness measures and psychotherapy outcomes. We report data from 76 studies, encompassing 25,917 patients. Moderate‐sized effects (d = 0.41) were found for the association among multiple disorders, including substance and alcohol use, eating disorders, and mood disorders. Outcomes were a function of the pretreatment stage of change; that is, the farther a patient along the stages, the better the treatment outcomes. This review added 37 studies to the data reported in 2010, further strengthening the link between readiness and therapy outcomes. The article concludes with limitations of the research, diversity considerations, and therapeutic practices for stage matching in psychotherapy specifically and behavioral health more generally.
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