Purpose:
Takayasu arteritis is a large-vessel vasculitis in women of childbearing age that affects large vessels including the aorta and its main branches. Inflammation of arteries can produce ...lesions that lead to occlusion, stenosis, or aneurysms which can lead to complications. If signs of organ dysfunction are present, vascular intervention may be necessary.
Case Report:
In this article, we present a case of Takayasu arteritis with high-grade stenosis of all the great vessels of the thoracic aorta treated with drug-coated balloon (DCB) angioplasty and stenting requiring multiple follow-up interventions over a 1-year follow-up.
Conclusion:
The DCB angioplasty is a potential endovascular treatment for thoracic great artery stenosis in Takayasu arteritis that could be further explored.
This study examines the association between changes in mental health before and during the COVID-19 pandemic and COVID-19 mortality across geographic areas and by race/ethnicity. A cross-sectional ...survey was conducted in Los Angeles County between April and May 2021. The study used the Patient Health Questionnaire-2 to assess major depression risk. Participants' home ZIP codes were classified into low, middle, and high COVID-19 mortality impacted areas (CMIA). While there were existing mental health disparities due to differences in demographics and social determinants of health across CMIA in 2018, the pandemic exacerbated the disparities, especially for residents living in high CMIA. Non-White residents in high CMIA reported the largest deterioration in mental health. Differences in mental health by CMIA persisted after controlling for resident characteristics. Living in an area with higher COVID-19 mortality rates may have been associated with worse mental health, with Non-White residents reporting worse mental health outcomes in the high mortality area.
► Glucocerebrosidase gene mutations are a risk factor for Parkinson’s disease. ► Glucocerebrosidase inhibition causes mitochondrial dysfunction & oxidative stress. ► These changes parallel important ...pathogenetic of Parkinson’s disease.
Mutations of the gene for glucocerebrosidase 1 (GBA) cause Gaucher disease (GD), an autosomal recessive lysosomal storage disorder. Individuals with homozygous or heterozygous (carrier) mutations of GBA have a significantly increased risk for the development of Parkinson’s disease (PD), with clinical and pathological features that mirror the sporadic disease. The mechanisms whereby GBA mutations induce dopaminergic cell death and Lewy body formation are unknown. There is evidence of mitochondrial dysfunction and oxidative stress in PD and so we have investigated the impact of glucocerebrosidase (GCase) inhibition on these parameters to determine if there may be a relationship of GBA loss-of-function mutations to the known pathogenetic pathways in PD. We have used exposure to a specific inhibitor (conduritol-β-epoxide, CβE) of GCase activity in a human dopaminergic cell line to identify the biochemical abnormalities that follow GCase inhibition. We show that GCase inhibition leads to decreased ADP phosphorylation, reduced mitochondrial membrane potential and increased free radical formation and damage, together with accumulation of alpha-synuclein. Taken together, inhibition of GCase by CβE induces abnormalities in mitochondrial function and oxidative stress in our cell culture model. We suggest that GBA mutations and reduced GCase activity may increase the risk for PD by inducing these same abnormalities in PD brain.
Wilson’s disease is a rare genetic condition that affects copper metabolism, resulting in tissue copper accumulation and resultant organ damage. We report a case of a young woman who presents with ...Wilson’s disease complicated by hemolysis, impaired hepatic function, coagulopathy, and acute kidney injury. She was treated with plasmapheresis as a bridge to a liver transplant. Her mental state, renal function, and bilirubin level improved after starting plasmapheresis. She successfully underwent a liver transplant and remained stable post-liver transplant. We share our experience on the use of plasmapheresis in treating Wilson’s disease.
Storm surges generated by tropical cyclones have been considered a primary process for building coarse‐sand beach ridges along the north‐eastern Queensland coast, Australia. This interpretation has ...led to the development of palaeotempestology based on the beach ridges. To better identify the sedimentary processes responsible for these ridges, a high‐resolution chronostratigraphic analysis of a series of ridges was carried out at Cowley Beach, Queensland, a meso‐tidal beach system with a >3 m tide range. Optically stimulated luminescence ages indicate that 10 ridges accreted seaward over the last 2500 to 2700 years. The ridge crests sit +3·5 to 5·1 m above Australian Height Datum (ca mean sea‐level). A ground‐penetrating radar profile shows two distinct radar facies, both of which are dissected by truncation surfaces. Hummocky structures in the upper facies indicate that the nucleus of the beach ridge forms as a berm at +2·5 m Australian Height Datum, equivalent to the fair‐weather swash limit during high tide. The lower facies comprises a sequence of seaward‐dipping reflections. Beach progradation thus occurs via fair‐weather‐wave accretion of sand, with erosion by storm waves resulting in a sporadic sedimentary record. The ridge deposits above the fair‐weather swash limit are primarily composed of coarse and medium sands with pumice gravels and are largely emplaced during surge events. Inundation of the ridges is more likely to occur in relation to a cyclone passing during high tide. The ridges may also include an aeolian component as cyclonic winds can transport beach sand inland, especially during low tide, and some layers above +2·5 m Australian Height Datum are finer than aeolian ripples found on the backshore. Coarse‐sand ridges at Cowley Beach are thus products of fair‐weather swash and cyclone inundation modulated by tides. Knowledge of this composite depositional process can better inform the development of robust palaeoenvironmental reconstructions from the ridges.
The effect of light on a model colloidal beverage system containing whey protein, lutein, and limonene was investigated. Changes in volatile chemistry were evaluated under accelerated conditions (12 ...h, 25 °C) at selected wavelengths regions (395, 463, 516, 567, and 610 nm absorbance maxima) using a photochemical reactor. The most damaging wavelengths to lutein stability were UV (200–400 nm) and 463 nm wavelengths. Hexanal formation was highest in the control beverage when exposed to full spectrum light and UV (200–400 nm) wavelengths. Hexanal also was formed in the lutein-fortified beverage under full spectrum light and UV (200–400 nm) wavelengths but to a significantly lesser degree. Limonene degraded significantly under all treatment conditions, with most degradation occurring during full spectrum light exposure. Lutein fortification did not completely protect limonene from degradation.
Key ecological features (KEFs) are elements of Australia’s Commonwealth marine environment considered to be important for biodiversity or ecosystem function, yet many KEFs are poorly researched, ...which can impede effective decision-making about future development and conservation. This study investigates a KEF positioned over the Last Glacial Maximum (LGM) shoreline on the northwest shelf of Australia (known as the ‘Ancient Coastline at ~125m depth contour’; AC125). Seafloor bathymetry, sedimentology and benthic habitats were characterised within five study areas using multibeam sonar, sediment samples and towed video imagery. Direct evidence for the existence of a palaeoshoreline formed during the LGM was not found, however candidate areas to find palaeoshoreline material at or just below the modern seabed were discovered. Approximately 98% of the seabed surveyed was comprised of unconsolidated soft sediment habitat (mud/sand/silt) supporting negligible epibenthic biota. The prevalence of soft sediment suggests that post-glacial sediments have infilled parts of the palaeoshoreline, with cross-shelf, probably tidal currents in the northern section of the study area responsible for some of the sediment mobilisation and southern study areas more influenced by oceanic conditions. Within study areas, total biotic cover ranged from 0.02% to 1.07%. Of the biota encountered, most comprised filter feeder organisms (including gorgonians, sponges, and whip corals) whose distribution was associated with pockets of consolidated hard substrate. Benthic community composition varied with both study area and position in relation to the predicted AC125. In general, consolidated substrate was proportionally higher in water shallower than the AC125 compared to on the AC125 or deeper than the AC125. Spatially continuous maps of predicted benthic habitat classes (pre-determined benthic communities) in each study area were developed to characterise biodiversity. Spatial modelling corroborated depth and large-scale structural complexity of the seafloor as surrogates for predicting likely habitat class. This study provides an important assessment of the AC125 and shows that if a distinct coastline exists in the areas we surveyed, it is now largely buried and as such does not provide a unique hard substrate habitat. However, much work remains to fully locate and map the ancient coastline within the vast region of the AC125 and additional surveys in shallow waters adjacent to the AC125 may identify whether some sections lie outside the currently defined KEF.
Germline pathogenic TP53 variants predispose individuals to a high lifetime risk of developing multiple cancers and are the hallmark feature of Li-Fraumeni syndrome (LFS). Our group has previously ...shown that LFS patients harbor shorter plasma cell-free DNA fragmentation; independent of cancer status. To understand the functional underpinning of cfDNA fragmentation in LFS, we conducted a fragmentomic analysis of 199 cfDNA samples from 82 TP53 mutation carriers and 30 healthy TP53-wildtype controls. We find that LFS individuals exhibit an increased prevalence of A/T nucleotides at fragment ends, dysregulated nucleosome positioning at p53 binding sites, and loci-specific changes in chromatin accessibility at development-associated transcription factor binding sites and at cancer-associated open chromatin regions. Machine learning classification resulted in robust differentiation between TP53 mutant versus wildtype cfDNA samples (AUC-ROC = 0.710–1.000) and intra-patient longitudinal analysis of ctDNA fragmentation signal enabled early cancer detection. These results suggest that cfDNA fragmentation may be a useful diagnostic tool in LFS patients and provides an important baseline for cancer early detection.Here, Wong et al investigate the cell-free DNA landscape of individuals with Li-Fraumeni syndrome (LFS), a cancer predisposition, and find altered composition compared to non-LFS individuals which can be used to detect and track cancer development.
Mutations of the gene for PTEN-induced kinase 1 (PINK1) are a cause of familial Parkinson's disease (PD). PINK1 protein has been localised to mitochondria and PINK1 gene knockout models exhibit ...abnormal mitochondrial function. The purpose of this study was to determine whether cells derived from PD patients with a range of PINK1 mutations demonstrate similar defects of mitochondrial function, whether the nature and severity of the abnormalities vary between mutations and correlate with clinical features.
We investigated mitochondrial bioenergetics in live fibroblasts from PINK1 mutation patients using single cell techniques. We found that fibroblasts from PINK1 mutation patients had significant defects of bioenergetics including reduced mitochondrial membrane potential, altered redox state, a respiratory deficiency that was determined by substrate availability, and enhanced sensitivity to calcium stimulation and associated mitochondrial permeability pore opening. There was an increase in the basal rate of free radical production in the mutant cells. The pattern and severity of abnormality varied between different mutations, and the less severe defects in these cells were associated with later age of onset of PD.
The results provide insight into the molecular pathology of PINK1 mutations in PD and also confirm the critical role of substrate availability in determining the biochemical phenotype--thereby offering the potential for novel therapeutic strategies to circumvent these abnormalities.
Thrombotic microangiopathies (TMA) are a rare group of life-threatening hematological conditions characterized by thrombocytopenia and microangiopathic hemolytic anemia. Although our understanding of ...the pathophysiology and the availability of diagnostic testing has improved for primary TMAs, such as thrombotic thrombocytopenic purpura, the pathophysiology underlying secondary TMAs, including drug-induced TMAs (DITMAs), remains less clear. In this case report, we present the unique case of a patient with a history of multiple myeloma that presented four months after the initiation of bortezomib therapy with a bortezomib-associated TMA that responded to therapeutic plasma exchange (TPE) with plasma replacement and eculizumab therapy. This case demonstrates the possible utility of TPE with plasma replacement and eculizumab therapy in DITMA patients that fail to respond following a trial of holding the suspected medication.
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