Adjuvant Botulinum Toxin Type A on the Management of Giant Hiatal Hernia: A Case Report.

The management of giant hiatal hernias (HHs) remains challenging and is associated with a high risk of recurrence. Currently, several strategies are used to reduce recurrence, and a newly proposed trend is the administration of adjuvant botulinum toxin type A (BTX), a procedure already performed in complex ventral hernias. Here, we present a case of a 63-year-old man with a giant paraesophageal HH type IV containing the entire stomach and transverse colon with loss of domain, who underwent adjuvant BTX and subsequently laparoscopic hiatoplasty with a biological mesh with partial fundoplication.

Telomere length is an epigenetic trait - Implications for the use of telomerase-deficient organisms to model human disease.

Telomere length, unlike most genetic traits, is epigenetic, in the sense that it is not fully coded by the genome. Telomeres vary in length and randomly assort to the progeny leaving some individuals with longer and others with shorter telomeres. Telomerase activity counteracts this by extending telomeres in the germline and during embryogenesis but sizeable variances remain in telomere length.

Lead to hit ruthenium-cyclopentadienyl anticancer compounds: Cytotoxicity against breast cancer cells, metabolic stability and metabolite profiling.

The successful choice of hit compounds during drug development programs involves the integration of structure-activity relationship (SAR) studies with pharmacokinetic determinations, including metabolic stability assays and metabolite profiling. A panel of nine ruthenium-cyclopentadienyl (RuCp) compounds with the general formula [Ru(η-CHR)(PPh)(bipyR')] (with R = H, CHO, CHOH; R' = H, CH, CHOH, CHBiotin) has been tested against hormone-dependent MCF-7 and triple negative MDA-MB-231 breast cancer cells. In general, all compounds showed important cytotoxicity against both cancer cell lines and were able to inhibit the formation of MDA-MB-231 colonies in a dose-dependent manner, while showing selectivity for cancer cells over normal fibroblasts.

A p21-GFP zebrafish model of senescence for rapid testing of senolytics in vivo.

Senescence drives the onset and severity of multiple ageing-associated diseases and frailty. As a result, there has been an increased interest in mechanistic studies and in the search for compounds targeting senescent cells, known as senolytics. Mammalian models are commonly used to test senolytics and generate functional and toxicity data at the level of organs and systems, yet this is expensive and time consuming.

A subset of gut leukocytes has telomerase-dependent "hyper-long" telomeres and require telomerase for function in zebrafish.

Background: Telomerase, the enzyme capable of elongating telomeres, is usually restricted in human somatic cells, which contributes to progressive telomere shortening with cell-division and ageing. T and B-cells cells are somatic cells that can break this rule and can modulate telomerase expression in a homeostatic manner. Whereas it seems intuitive that an immune cell type that depends on regular proliferation outbursts for function may have evolved to modulate telomerase expression it is less obvious why others may also do so, as has been suggested for macrophages and neutrophils in some chronic inflammation disease settings.

Müller Glia maintain their regenerative potential despite degeneration in the aged zebrafish retina.

Ageing is a significant risk factor for degeneration of the retina. Müller glia cells (MG) are key for neuronal regeneration, so harnessing the regenerative capacity of MG in the retina offers great promise for the treatment of age-associated blinding conditions. Yet, the impact of ageing on MG regenerative capacity is unclear.

Resident Immunity in Tissue Repair and Maintenance: The Zebrafish Model Coming of Age.

The zebrafish has emerged as an exciting vertebrate model to study different aspects of immune system development, particularly due to its transparent embryonic development, the availability of multiple fluorescent reporter lines, efficient genetic tools and live imaging capabilities. However, the study of immunity in zebrafish has largely been limited to early larval stages due to an incomplete knowledge of the full repertoire of immune cells and their specific markers, in particular, a lack of cell surface antibodies to detect and isolate such cells in living tissues. Here we focus on tissue resident or associated immunity beyond development, in the adult zebrafish.

The Zebrafish as an Emerging Model to Study DNA Damage in Aging, Cancer and Other Diseases.

Cancer is a disease of the elderly, and old age is its largest risk factor. With age, DNA damage accumulates continuously, increasing the chance of malignant transformation. The zebrafish has emerged as an important vertebrate model to study these processes.

Generation of Gellan Gum-Based Adipose-Like Microtissues.

Adipose tissue is involved in many physiological processes. Therefore, the need for adipose tissue-like analogues either for soft tissue reconstruction or as in vitro testing platforms is undeniable. In this work, we explored the natural features of gellan gum (GG) to recreate injectable stable adipose-like microtissues.

How to Catch a Smurf? - Ageing and Beyond… Assessment of Intestinal Permeability in Multiple Model Organisms.

The Smurf Assay (SA) was initially developed in the model organism where a dramatic increase of intestinal permeability has been shown to occur during aging (Rera , 2011). We have since validated the protocol in multiple other model organisms (Dambroise , 2016) and have utilized the assay to further our understanding of aging (Tricoire and Rera, 2015; Rera , 2018). The SA has now also been used by other labs to assess intestinal barrier permeability (Clark , 2015; Katzenberger , 2015; Barekat , 2016; Chakrabarti , 2016; Gelino , 2016).

Correction: Telomerase Is Required for Zebrafish Lifespan.

[This corrects the article DOI: 10.1371/journal.pgen.

Interventions for age-related diseases: Shifting the paradigm.

Over 60% of people aged over 65 are affected by multiple morbidities, which are more difficult to treat, generate increased healthcare costs and lead to poor quality of life compared to individual diseases. With the number of older people steadily increasing this presents a societal challenge. Age is the major risk factor for age-related diseases and recent research developments have led to the proposal that pharmacological interventions targeting common mechanisms of ageing may be able to delay the onset of multimorbidity.

Short Telomeres in Key Tissues Initiate Local and Systemic Aging in Zebrafish.

Telomeres shorten with each cell division and telomere dysfunction is a recognized hallmark of aging. Tissue proliferation is expected to dictate the rate at which telomeres shorten. We set out to test whether proliferative tissues age faster than non-proliferative due to telomere shortening during zebrafish aging.

Telomerase is required for zebrafish lifespan.

Telomerase activity is restricted in humans. Consequentially, telomeres shorten in most cells throughout our lives. Telomere dysfunction in vertebrates has been primarily studied in inbred mice strains with very long telomeres that fail to deplete telomeric repeats during their lifetime.

Consequences of telomere shortening during lifespan.

Telomerase expression is restricted in human cells and so telomeres shorten throughout our lives, providing a tumour suppressor mechanism that limits cell proliferation. As a trade-off, continuous telomere erosion results in replicative senescence and contributes to ageing. Recently, telomerase therapies were proposed as a valid approach to rescue degenerative phenotypes caused by telomere dysfunction.

IL-7 induces rapid clathrin-mediated internalization and JAK3-dependent degradation of IL-7Ralpha in T cells.

Interleukin-7 (IL-7) is an essential cytokine for T-cell development and homeostasis. It is well established that IL-7 promotes the transcriptional down-regulation of IL7RA, leading to decreased IL-7Ralpha surface expression. However, it is currently unknown whether IL-7 regulates the intracellular trafficking and early turnover of its receptor on ligand binding.

Centrifugal elutriation as a means of cell cycle phase separation and synchronisation.

The ability to purify cells in specific phases of the cell cycle in sufficient quantities for biochemical analysis or to obtain a "synchronized" population of living cells enriched in a particular phase is of great value for studying a wide range of cell cycle processes. Transformed tumour cell lines, such as DT40, can be arrested and released from specific points in the cell cycle using drugs which inhibit DNA or protein synthesis or interfere with mitotic spindle function, however such drugs are frequently toxic and may themselves perturb the cell cycle process or phenomenon under study. Centrifugal elutriation provides a means of separating an unperturbed culture of living cells into highly enriched G1-, S-, and G2/ M-phase fractions.