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Diabetes mellitus remains a major public health problem throughout the United States with over $300 billion spent in total cost of care annually. In addition to being a leading cost of kidney failure, diabetes causes a host of secondary hyperglycemic-related complications including gastroparesis and orthostatic hypotension. While pancreas transplantation has been established as an effective treatment for diabetes, providing long-term normoglycemia in recipients, the secondary complications of diabetes mellitus persist complicating the post-operative course of an otherwise successful pancreas transplantation. This review describes the mechanism and impact of diabetic gastroparesis and orthostatic hypotension in the post-operative course of pancreas transplant patients and analyzes the various treatment modalities, based on current data and extensive experience at our institution, to treat these respective complications. While gastroparesis and orthostatic hypotension remain challenging post-operative conditions, the establishment of institutional protocols and step-up treatment algorithms can help define more effective therapies.Genome haploidization involves sequential loss of cohesin from chromosome arms and centromeres during two meiotic divisions. At centromeres, cohesin's Rec8 subunit is protected from separase cleavage at meiosis I and then deprotected to allow its cleavage at meiosis II. Protection of centromeric cohesin by shugoshin-PP2A seems evolutionarily conserved. However, deprotection has been proposed to rely on spindle forces separating the Rec8 protector from cohesin at metaphase II in mammalian oocytes and on APC/C-dependent destruction of the protector at anaphase II in yeast. Here, we have activated APC/C in the absence of sister kinetochore biorientation at meiosis II in yeast and mouse oocytes, and find that bipolar spindle forces are dispensable for sister centromere separation in both systems. Furthermore, we show that at least in yeast, protection of Rec8 by shugoshin and inhibition of separase by securin are both required for the stability of centromeric cohesin at metaphase II. Our data imply that related mechanisms preserve the integrity of dyad chromosomes during the short metaphase II of yeast and the prolonged metaphase II arrest of mammalian oocytes.We evaluated the effect of phytic acid on matrix metalloproteinase (MMP)- or cysteine cathepsin (CC)-mediated dentin degradation. Demineralized dentin beams were divided into five groups (n = 12) and treated with 1%, 2%, or 3% phytic acid or with 37% phosphoric acid. Untreated demineralized beams served as controls. After incubation for 1 or 3 wk, dry mass loss was determined and aliquots of incubation media were analysed for cross-linked telopeptide of type I collagen (ICTP) fragments for MMP-mediated and c-terminal telopeptide of type I collagen (CTX) for cathepsin-k-mediated degradation. The direct effect of phytic acid was evaluated using MMP activity assay. Data were analysed using repeated-measures anova. ICTP releases with 1% and 2% phytic acid treatment were statistically significantly lower than those following phosphoric acid treatment at 3 wk. The CTX release for phytic acid-treated beams at 3 wk was not significantly different from that of untreated control beams, but it was significantly lower than that of phosphoric acid-treated beams. Their MMP activities at 3 wk were not significantly different from those of the controls but they were significantly lower than those seen for phosphoric acid-treated beams. Compared to phosphoric acid, phytic acid treatment resulted in a reduced dentinal host-derived endogenous enzymatic activity and collagen degradation.Partitioning of the genome in meiosis occurs through two highly specialized cell divisions, named meiosis I and meiosis II. Step-wise cohesin removal is required for chromosome segregation in meiosis I, and sister chromatid segregation in meiosis II. In meiosis I, mono-oriented sister kinetochores appear as fused together when examined by high-resolution confocal microscopy, whereas they are clearly separated in meiosis II, when attachments are bipolar. It has been proposed that bipolar tension applied by the spindle is responsible for the physical separation of sister kinetochores, removal of cohesin protection, and chromatid separation in meiosis II. We show here that this is not the case, and initial separation of sister kinetochores occurs already in anaphase I independently of bipolar spindle forces applied on sister kinetochores, in mouse oocytes. This kinetochore individualization depends on separase cleavage activity. Crucially, without kinetochore individualization in meiosis I, bivalents when present in meiosis II oocytes separate into chromosomes and not sister chromatids. This shows that whether centromeric cohesin is removed or not is determined by the kinetochore structure prior to meiosis II.
Vaccine hesitancy poses serious challenges for achieving coverage for population immunity. It is necessary to achieve high COVID-19 vaccination acceptance rates and medical students' coverage as future health care providers. The study aimed to explore the level of COVID-19 vaccine hesitancy and determine the factors and barriers that may affect vaccination decision-making.
A cross-sectional study was carried out among medical students in Tanta and Kafrelsheikh Universities, Egypt. Data collection was done via an online questionnaire during January 2021 from 2133 students.
The majority of the participant students (90.5%) perceived the importance of the COVID-19 vaccine, 46% had vaccination hesitancy, and an equal percentage (6%) either definitely accepted or refused the vaccine. Most of the students had concerns regarding the vaccine's adverse effects (96.8%) and ineffectiveness (93.2%). The most confirmed barriers of COVID-19 vaccination were deficient data regarding the vaccine's adverse effects (potential 74.17% and unknown 56.31%) and insufficient information regarding the vaccine itself (72.76%).
The government, health authority decision-makers, medical experts, and universities in Egypt need to work together and make efforts to reduce hesitancy and raise awareness about vaccinations, consequently improving the acceptance of COVID-19 vaccines.
The government, health authority decision-makers, medical experts, and universities in Egypt need to work together and make efforts to reduce hesitancy and raise awareness about vaccinations, consequently improving the acceptance of COVID-19 vaccines.Animal models of invasive fungal infections have been developed and are applied in a huge number of different animal species for a number of research purposes, for example, the study of pathogenesis, defense mechanisms, and therapeutic strategies. From the different models, which in most cases are based on the same fungal species and often the same strain, as in spontaneous human infections, fundamental results and knowledge of the diagnosis, progression, prophylaxis, and therapy have been achieved. However, in all models, one should be critical with respect to mimicking the disease entity of humans, which is often the focus of the research. In many of the models for instance, the time course is different to the one of humans, and in others, the propensity for localization and containment in specific organs does not parallel the situation in humans. Nevertheless, many animal models of invasive mycoses have proven valuable in a number of research areas. With regard to new generations of anti-mycotic drugs, the models play an essential role in demonstrating antifungal activity, as well as in demonstrating the absence of toxic side effects, a critical step which cannot be accomplished by in vitro studies.
To propose a method for voxel-wise estimation of cell radii and volume fractions of two cell populations when they coexist in the same MR voxel using the combination of diffusion-weighted MRI and microstructural modeling.
Microstructure models were investigated using diffusion data simulated with the matrix method for a range of microstructures mimicking tumor tissue with two cell populations, using acquisition parameters available on preclinical scanners. The effect of noise was investigated for a subset of these microstructures. The accuracy and precision of the estimated radii and volume fractions for large and small cells
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for voxel-wise estimation of cell radii and volume fractions of two cell populations when they coexist in the same MR voxel. IACS-13909 solubility dmso The ability to reliably characterize tissue with two cell populations opens exciting avenues of potential applications in both tumor diagnosis and treatment monitoring.The present research investigated whether learning that an outgroup humanizes the ingroup (i.e., meta-humanization) enhances how people react to intergroup prosocial behaviours and their willingness to engage in intergroup contact. In three experiments conducted in two cultural contexts (Kosovo and North Macedonia; n = 601), we manipulated meta-humanization by informing participants that their ingroup is perceived to be as human as the outgroup by outgroup members. We compare this meta-humanization condition with a meta-dehumanization condition in which the participant's ingroup is perceived to be less human than the outgroup (Experiments 1 and 3), a meta-liking condition in which the participant's ingroup is liked as much as the outgroup (Experiment 2), and a control condition (Experiments 1 and 2). Overall, results showed that participants in the meta-humanization condition attributed more empathy and prosocial motives to a potential outgroup helper and were more willing to accept outgroup help and engage in future intergroup contact than participants in the other conditions. In addition, positive perceptions of the outgroup helper mediated the effect of meta-humanization on willingness to accept outgroup help and engage in intergroup contact. We discuss the theoretical and practical implications of these findings for intergroup relations and reconciliation efforts.
Sociocultural theories hold that family and peer weight-related teasing increases the risk for unhealthy weight control behaviors (UWCBs) by negatively impacting body image. Although much cross-sectional support exists for these pathways, longitudinal data are lacking. This study tested the longitudinal relationships among peer and family teasing (occurrence and perceived impact) in early adolescence, body satisfaction in late adolescence, and UWCBs in young adulthood among a racially/ethnically and socioeconomically diverse population.
Data were drawn from three waves of Project EAT over a 15-year period (Eating and Activity in Teens and Young Adults), and included responses from 1,902 young adults (57% female).
Among female participants, a mediated indirect pathway emerged with family weight-related teasing predicting increased engagement in UWCBs in early adulthood via poorer body image in late adolescence. In contrast, peer teasing did not predict body image or UWCBs. Among boys, the mediated indirect pathways were not significant.
