Tissue engineered vascular grafts transform into autologous neovessels capable of native function and growth

Background Tissue-engineered vascular grafts (TEVGs) have the potential to advance the surgical management of infants and children requiring congenital heart surgery by creating functional vascular conduits with growth capacity. Methods Herein, we used an integrative computational-experimental approach to elucidate the natural history of neovessel formation in a large animal preclinical model; combining an in vitro accelerated degradation study with mechanical testing, large animal implantation studies with in vivo imaging and histology, and data-informed computational growth and remodeling models. Results Our findings demonstrate that the structural integrity of the polymeric scaffold is lost over the first 26 weeks in vivo, while polymeric fragments persist for up to 52 weeks. Our models predict that early neotissue accumulation is driven primarily by inflammatory processes in response to the implanted polymeric scaffold, but that turnover becomes progressively mechano-mediated as the scaffold degrades. Using a lamb model, we confirm that early neotissue formation results primarily from the foreign body reaction induced by the scaffold, resulting in an early period of dynamic remodeling characterized by transient TEVG narrowing. As the scaffold degrades, mechano-mediated neotissue remodeling becomes dominant around 26 weeks. After the scaffold degrades completely, the resulting neovessel undergoes growth and remodeling that mimicks native vessel behavior, including biological growth capacity, further supported by fluid–structure interaction simulations providing detailed hemodynamic and wall stress information. Conclusions These findings provide insights into TEVG remodeling, and have important implications for clinical use and future development of TEVGs for children with congenital heart disease.

Listeria monocytogenes Sublethal Injury and Viable-but-Nonculturable State Induced by Acidic Conditions and Disinfectants

Sublethally injured and VBNC cells may evade detection, resulting in underestimation of a food product’s microbial load. Under favorable conditions, cells may regain their growth capacity and acquire new resistant characteristics, posing a major threat for public health.

The Price of Surviving on Adrenaline: Developmental Programming Responses to Chronic Fetal Hypercatecholaminemia Contribute to Poor Muscle Growth Capacity and Metabolic Dysfunction in IUGR-Born Offspring

Maternofetal stress induces fetal programming that restricts skeletal muscle growth capacity and metabolic function, resulting in intrauterine growth restriction (IUGR) of the fetus. This thrifty phenotype aids fetal survival but also yields reduced muscle mass and metabolic dysfunction after birth. Consequently, IUGR-born individuals are at greater lifelong risk for metabolic disorders that reduce quality of life. In livestock, IUGR-born animals exhibit poor growth efficiency and body composition, making these animals more costly and less valuable. Specifically, IUGR-associated programming causes a greater propensity for fat deposition and a reduced capacity for muscle accretion. This, combined with metabolic inefficiency, means that these animals produce less lean meat from greater feed input, require more time on feed to reach market weight, and produce carcasses that are of less quality. Despite the health and economic implications of IUGR pathologies in humans and food animals, knowledge regarding their specific underlying mechanisms is lacking. However, recent data indicate that adaptive programing of adrenergic sensitivity in multiple tissues is a contributing factor in a number of IUGR pathologies including reduced muscle mass, peripheral insulin resistance, and impaired glucose metabolism. This review highlights the findings that support the role for adrenergic programming and how it relates to the lifelong consequences of IUGR, as well as how dysfunctional adrenergic signaling pathways might be effective targets for improving outcomes in IUGR-born offspring.

Genome-wide chromatin accessibility analyses provide a map for enhancing optic nerve regeneration

Retinal Ganglion Cells (RGCs) lose their ability to grow axons during development. Adult RGCs thus fail to regenerate their axons after injury, leading to vision loss. To uncover mechanisms that promote regeneration of RGC axons, we identified transcription factors (TF) and open chromatin regions that are enriched in rat embryonic RGCs (high axon growth capacity) compared to postnatal RGCs (low axon growth capacity). We found that developmental stage-specific gene expression changes correlated with changes in promoter chromatin accessibility. Binding motifs for TFs such as CREB, CTCF, JUN and YY1 were enriched in the regions of the chromatin that were more accessible in embryonic RGCs. Proteomic analysis of purified rat RGC nuclei confirmed the expression of TFs with potential role in axon growth such as CREB, CTCF, YY1, and JUND. The CREB/ATF binding motif was widespread at the open chromatin region of known pro-regenerative TFs, supporting a role of CREB in regulating axon regeneration. Consistently, overexpression of CREB fused to the VP64 transactivation domain in mouse RGCs promoted axon regeneration after optic nerve injury. Our study provides a map of the chromatin accessibility during RGC development and highlights that TF associated with developmental axon growth can stimulate axon regeneration in mature RGC.

Co-targeting myelin inhibitors and CSPGs markedly enhances regeneration of GDNF-stimulated, but not conditioning-lesioned, sensory axons into the spinal cord

A major barrier to intraspinal regeneration after dorsal root (DR) injury is the DR entry zone (DREZ), the CNS/PNS interface. DR axons stop regenerating at the DREZ, even if regenerative capacity is increased by a nerve conditioning lesion. This potent blockade has long been attributed to myelin-associated inhibitors and CSPGs, but incomplete lesions and conflicting reports have prevented conclusive agreement. Here we evaluated DR regeneration in mice, using novel strategies to facilitate complete lesions and analyses, selective tracing of proprioceptive and mechanoreceptive axons, and the first simultaneous targeting of Nogo/Reticulon-4, MAG, OMgp, CSPGs and GDNF. Co-eliminating myelin inhibitors and CSPGs elicited regeneration of only a few conditioning-lesioned DR axons across the DREZ. Their absence, however, markedly and synergistically enhanced regeneration of GDNF-stimulated axons, highlighting the importance of sufficiently elevating intrinsic growth capacity. We also conclude that myelin inhibitors and CSPGs are not the primary mechanism stopping axons at the DREZ.

Genome-wide chromatin accessibility analyses provide a map for enhancing optic nerve regeneration

Retinal Ganglion Cells (RGCs) lose their ability to grow axons during development. Adult RGCs thus fail to regenerate their axons after injury, leading to vision loss. To uncover mechanisms that promote RGC axon regeneration, we identified transcription factors (TF) and chromatin accessible sites enriched in embryonic RGCs (high axon growth capacity) compared to postnatal RGC (low axon growth capacity). Developmental stage-specific gene expression changes correlated with changes in promoter chromatin accessibility. Binding motifs for TFs such as CREB, CTCF, JUN and YY1 were enriched in the differentially opened regions of the chromatin in embryonic RGCs and proteomic analysis confirmed their expression in RGC nuclei. The CREB/ATF binding motif was widespread at the open chromatin region of known pro-regenerative TFs, supporting a role of CREB in regulating axon growth. Consistently, overexpression of CREB fused to the VP64 transactivation domain in RGCs promoted axon regeneration after optic nerve injury. Our study provides a map of the chromatin accessibility during RGC development and highlights that TF associated with developmental axon growth can stimulate axon regeneration in mature RGC.

Radiotherapy for large recurrent ameloblastoma of the mandible previously treated by surgery: A case report

Ameloblastoma is a benign odontogenic tumor. It is locally invasive and unlimited growth capacity, with a propensity for recurrence if not entirely excised. The therapeutic challenge in this type of tumors is to have an adequate resection with a wide margin of normal tissue but also a functional and aesthetically acceptable reconstruction of the residual defect. The role of radiotherapy is currently demonstrated in inoperable cases. We are reporting a case of a 45 years-old male patient with large ameloblastoma of the mandible recurrent 10 years after surgical resection. The patient benefited from exclusive radiotherapy at a dose of 60 Gy.

Financial performance analysis of GIC Re

Purpose This study aims to analyse the following: first, the financial performance of General Insurance Re (GIC Re) using performance ratios (PRs); second, the uniformity of different financial performance indicators of GIC Re; third, the internal growth capacity of GIC Re; and finally, the likelihood of GIC Re going into financial distress. Design/methodology/approach As a sample, GIC Re, the lion shareholder in Indian Reinsurance Industry has been considered in the present study. All the necessary data have been extracted from the secondary sources over a time period of 16 years. The financial performance of GIC Re is assessed using five standard ratios, and the uniformity of different financial performance indicators of GIC Re has been examined using Kendall’s Coefficient of Concordance (W). To assess the internal growth capacity of GIC Re internal growth rate has been used, and the likelihood of GIC Re going into financial distress is analysed using multivariate discriminant approach, namely, modified Altman’s Z-score model and logit analysis technique, namely, Ohlson’s O-score model. Findings The results exhibit that financial performance of GIC Re is somewhat satisfactory over a few considerable areas. However, no notable degree of uniformity has been observed amongst the varied financial performance indicators, namely, performance ratio, expense ratio, return on assets, risk retention ratio and combined ratio of GIC Re. The results also reveal GIC Re is lacking ability of growing internally. Moreover, there remains a significant possibility of GIC Re going into financial distress in the near future and so. Originality/value This study is one of the first empirical research studies in India that examines the financial performance of GIC Re from different perspectives.