Search

Purpose: Radiation therapy is an independent risk factor for adverse sequelae to the oral cavity and dentition in childhood cancer survivors. However, dental toxicities after radiation therapy often are underreported and there are minimal published data on disturbances in tooth development after proton beam therapy (PBT). We present the long-term clinical and radiographic dental findings 8 years after treatment completion for a patient treated with PBT and chemotherapy for rhabdomyosarcoma. Materials and Methods: Clinical follow-up data of patients treated with PBT within the Proton Overseas Programme (POP) is stored in a National Database and curated by a dedicated outcomes unit at the Christie NHS PBT center. This case report was identified from the extraction and analysis of data for pediatric head and neck cancer patients in this database for a service evaluation project. Results: The permanent dentition in this patient aged 3.5 years at the time of treatment was severely affected with abnormal dental development first observed 3.5 years after treatment completion. PBT delivered mean doses of 30 Gy(RBE = 1.1) to the maxilla and 25.9 Gy(RBE = 1.1) to the mandible. Conclusion: Significant dental development abnormalities occurred in this pediatric patient, despite doses in areas being lower than the proposed thresholds in the literature. Improved descriptions of dental toxicities and routine contouring of the maxilla and mandible are needed to correlate dosimetric data. The dose to teeth should be kept as low as reasonably possible in younger patients until the dose thresholds for dental toxicities are known.

The use of antioxidants could thus prove an effective medication to prevent or facilitate recovery from oxidative stress-induced sensorineural hearing loss (SNHL). One promising strategy to prevent SNHL is developing probucol (PB)-based nanoparticles using encapsulation technology and administering them to the inner ear via the established intratympanic route. The preclinical, clinical and epidemiological studies support that PB is a proven antioxidant that could effectively prevent oxidative stress in different study models. Such findings suggest its applicability in preventing oxidative stress within the inner ear and its associated neural cells. However, several hurdles, such as overcoming the blood-labyrinth barrier, ensuring sustained release, minimising systemic side effects and optimising targeted delivery in the intricate inner ear structures, must be overcome to efficiently deliver PB to the inner ear. This review explores the background and pathogenesis of hearing loss, the potential of PB in treating oxidative stress and its cellular mechanisms, and the obstacles linked to inner ear drug delivery for effectively introducing PB to the inner ear. [ABSTRACT FROM AUTHOR]

Background / Aim: Metformin is widely used in type 2 diabetes and exhibits many positive biological effects on pancreatic b-cells and muscle cells, such as supporting insulin release by b-cells and glucose uptake by muscle cells and reducing oxidative stress, particularly due to diabetes-associated hyperglycaemia. Interestingly, for type 1 diabetes, transplantation of healthy b-cells has been proposed as a novel way to replace insulin therapy. Recently, bile acid-formulations containing transplantable b-cells showed best stability. Hence, this study aimed to explore the effects of metformin-bile acid formulations in b-cell encapsulation and on the biological activities of b-cells and muscle-cells. Methods: Two sets of biological effects were examined, using metformin-bile acid formulations, on encapsulated b-cells and on muscle cells exposed to the formulations. Results: Various encapsulated b-cell formulations' cell viability, insulin levels, cellular oxidative stress, cellular inflammatory profile and bioenergetics at the normoand hyperglycaemic states showed differing results based upon the metformin concentration and the inclusion or absence of bile acid. Similar effects were observed with muscle cells. Low ratios of metformin and bile acids showed best biological effects, suggesting a formulation dependent result. The formulations' positive effects were more profound at the hyperglycaemic state suggesting efficient cell protective effects. Conclusion: Overall, metformin had positive impacts on the cells in a concentration-dependent manner, with the addition of chenodeoxycholic acid further improving results.

There are sex differences in vulnerability and resilience to the stressors of aging and subsequent age-related cognitive decline. Cellular senescence occurs as a response to damaging or stress-inducing stimuli. The response includes a state of irreversible growth arrest, the development of a senescence- associated secretory phenotype, and the release of pro-inflammatory cytokines associated with aging and age-related diseases. Senolytics are compounds designed to eliminate senescent cells. Our recent work indicates that senolytic treatment preserves cognitive function in aging male F344 rats. The current study examined the effect of senolytic treatment on cognitive function in aging female rats. Female F344 rats (12 months) were treated with dasatinib (1.2 mg/kg) + quercetin (12 mg/kg) or ABT-263 (12 mg/kg) or vehicle for 7 months. Examination of the estrus cycle indicated that females had undergone estropause during treatment. Senolytic treatment may have increased sex differences in behavioral stress responsivity, particularly for the initial training on the cued version of the watermaze. However, pre-training on the cue task reduced stress responsivity for subsequent spatial training and all groups learned the spatial discrimination. In contrast to preserved memory observed in senolytic-treated males, all older females exhibited impaired episodic memory relative to young (6-month) females. We suggest that the senolytic treatment may not have been able to compensate for the loss of estradiol, which can act on aging mechanisms for anxiety and memory independent of cellular senescence. [ABSTRACT FROM AUTHOR]

African swine fever (ASF) is a devastating disease of domestic pigs that has spread across the globe since its introduction into Georgia in 2007. The etiological agent is a large double-stranded DNA virus with a genome of 170 to 180 kb in length depending on the isolate. Much of the differences in genome length between isolates are due to variations in the copy number of five different multigene families that are encoded in repetitive regions that are towards the termini of the covalently closed ends of the genome. Molecular epidemiology of African swine fever virus (ASFV) is primarily based on Sanger sequencing of a few conserved and variable regions, but due to the stability of the dsDNA genome changes in the variable regions occur relatively slowly. Observations in Europe and Asia have shown that changes in other genetic loci can occur and that this could be useful in molecular tracking. ASFV has been circulating in Western Africa for at least forty years. It is therefore reasonable to assume that changes may have accumulated in regions of the genome other than the standard targets over the years. At present only one full genome sequence is available for an isolate from Western Africa, that of a highly virulent isolate collected from Benin during an outbreak in 1997. In Cameroon, ASFV was first reported in 1981 and outbreaks have been reported to the present day and is considered endemic. Here we report three full genome sequences from Cameroon isolates of 1982, 1994 and 2018 outbreaks and identify novel single nucleotide polymorphisms and insertion-deletions that may prove useful for molecular epidemiology studies in Western Africa and beyond. [ABSTRACT FROM AUTHOR]

Doxorubicin (Dox), a widely used treatment for cancer, can result in chemotherapy‐induced cognitive impairments (chemobrain). Chemobrain is associated with inflammation and oxidative stress similar to aging. As such, Dox treatment has also been used as a model of aging. However, it is unclear if Dox induces brain changes similar to that observed during aging since Dox does not readily enter the brain. Rather, the mechanism for chemobrain likely involves the induction of peripheral cellular senescence and the release of senescence‐associated secretory phenotype (SASP) factors and these SASP factors can enter the brain to disrupt cognition. We examined the effect of Dox on peripheral and brain markers of aging and cognition. In addition, we employed the senolytic, ABT‐263, which also has limited access to the brain. The results indicate that plasma SASP factors enter the brain, activating microglia, increasing oxidative stress, and altering gene transcription. In turn, the synaptic function required for memory was reduced in response to altered redox signaling. ABT‐263 prevented or limited most of the Dox‐induced effects. The results emphasize a link between cognitive decline and the release of SASP factors from peripheral senescent cells and indicate some differences as well as similarities between advanced age and Dox treatment. [ABSTRACT FROM AUTHOR]