Heme oxygenase-1 deficiency alters erythroblastic Island formation, steady-state erythropoiesis and red blood cell lifespan in mice

Heme oxygenase-1 is critical for iron recycling during red blood cell turnover, whereas its impact on steady-state erythropoiesis and red blood cell lifespan is not known. We show here that in 8- to 14-week old mice, heme oxygenase- 1 deficiency adversely affects steady-state erythropoiesis in the bone marrow. This is manifested by a decrease in Ter-119+-erythroid cells, abnormal adhesion molecule expression on macrophages and erythroid cells, and a greatly diminished ability to form erythroblastic islands. Compared with wild-type animals, red blood cell size and hemoglobin content are decreased, while the number of circulating red blood cells is increased in heme oxygenase-1 deficient mice, overall leading to microcytic anemia. Heme oxygenase-1 deficiency increases oxidative stress in circulating red blood cells and greatly decreases the frequency of macrophages expressing the phosphatidylserine receptor Tim4 in bone marrow, spleen and liver. Heme oxygenase-1 deficiency increases spleen weight and Ter119+-erythroid cells in the spleen, although α4β1-integrin expression by these cells and splenic macrophages positive for vascular cell adhesion molecule 1 are both decreased. Red blood cell lifespan is prolonged in heme oxygenase-1 deficient mice compared with wild-type mice. Our findings suggest that while macrophages and relevant receptors required for red blood cell formation and removal are substantially depleted in heme oxygenase- 1 deficient mice, the extent of anemia in these mice may be ameliorated by the prolonged lifespan of their oxidatively stressed erythrocytes

Associations of psychological wellbeing with COVID-19 hospitalization and mortality in adults aged 50 years or older from 25 European countries and Israel

BackgroundLower psychological wellbeing is associated with poor outcomes in a variety of diseases and healthy populations. However, no study has investigated whether psychological wellbeing is associated with the outcomes of COVID-19. This study aimed to determine whether individuals with lower psychological wellbeing are more at risk for poor outcomes of COVID-19.MethodsData were from the Survey of Health, Aging, and Retirement in Europe (SHARE) in 2017 and SHARE's two COVID-19 surveys in June–September 2020 and June–August 2021. Psychological wellbeing was measured using the CASP-12 scale in 2017. The associations of the CASP-12 score with COVID-19 hospitalization and mortality were assessed using logistic models adjusted for age, sex, body mass index, smoking, physical activity, household income, education level, and chronic conditions. Sensitivity analyses were performed by imputing missing data or excluding cases whose diagnosis of COVID-19 was solely based on symptoms. A confirmatory analysis was conducted using data from the English Longitudinal Study of Aging (ELSA). Data analysis took place in October 2022.ResultsIn total, 3,886 individuals of 50 years of age or older with COVID-19 were included from 25 European countries and Israel, with 580 hospitalized (14.9%) and 100 deaths (2.6%). Compared with individuals in tertile 3 (highest) of the CASP-12 score, the adjusted odds ratios (ORs) of COVID-19 hospitalization were 1.81 (95% CI, 1.41–2.31) for those in tertile 1 (lowest) and 1.37 (95% CI, 1.07–1.75) for those in tertile 2. As for COVID-19 mortality, the adjusted ORs were 2.05 (95% CI, 1.12–3.77) for tertile 1 and 1.78 (95% CI, 0.98–3.23) for tertile 2, compared with tertile 3. The results were relatively robust to missing data or the exclusion of cases solely based on symptoms. This inverse association of the CASP-12 score with COVID-19 hospitalization risk was also observed in ELSA.ConclusionThis study shows that lower psychological wellbeing is independently associated with increased risks of COVID-19 hospitalization and mortality in European adults aged 50 years or older. Further study is needed to validate these associations in recent and future waves of the COVID-19 pandemic and other populations

Impact of cardiac arrest centers on the survival of patients with nontraumatic out‐of‐hospital cardiac arrest : a systematic review and meta‐analysis

Background The role of cardiac arrest centers (CACs) in out‐of‐hospital cardiac arrest care systems is continuously evolving. Interpretation of existing literature is limited by heterogeneity in CAC characteristics and types of patients transported to CACs. This study assesses the impact of CACs on survival in out‐of‐hospital cardiac arrest according to varying definitions of CAC and prespecified subgroups. Methods and Results Electronic databases were searched from inception to March 9, 2021 for relevant studies. Centers were considered CACs if self‐declared by study authors and capable of relevant interventions. Main outcomes were survival and neurologically favorable survival at hospital discharge or 30 days. Meta‐analyses were performed for adjusted odds ratio (aOR) and crude odds ratios. Thirty‐six studies were analyzed. Survival with favorable neurological outcome significantly improved with treatment at CACs (aOR, 1.85 [95% CI, 1.52–2.26]), even when including high‐volume centers (aOR, 1.50 [95% CI, 1.18–1.91]) or including improved‐care centers (aOR, 2.13 [95% CI, 1.75–2.59]) as CACs. Survival significantly increased with treatment at CACs (aOR, 1.92 [95% CI, 1.59–2.32]), even when including high‐volume centers (aOR, 1.74 [95% CI, 1.38–2.18]) or when including improved‐care centers (aOR, 1.97 [95% CI, 1.71–2.26]) as CACs. The treatment effect was more pronounced among patients with shockable rhythm ( P =0.006) and without prehospital return of spontaneous circulation ( P =0.005). Conclusions were robust to sensitivity analyses, with no publication bias detected. Conclusions Care at CACs was associated with improved survival and neurological outcomes for patients with nontraumatic out‐of‐hospital cardiac arrest regardless of varying CAC definitions. Patients with shockable rhythms and those without prehospital return of spontaneous circulation benefited more from CACs. Evidence for bypassing hospitals or interhospital transfer remains inconclusive

The Erythroblastic Island: A new look at the erythroid niche

Globally, an estimated 25% of the global population suffer from anaemia. Despite extensive research over the past decade on red blood cell production (erythropoiesis), the mechanisms of erythropoiesis are not fully elucidated. The microenvironment in the bone marrow in which red blood cell progenitors proliferate and differentiate, known as the erythroid niche, is termed as the erythroblastic islands (EBIs). Despite the discovery of the EBIs was more than 50 years ago, the role of these erythroid niches in regulating erythropoiesis remains poorly understood. The aim of this study was to understand how EBIs regulate erythropoiesis, with the first goal of defining the erythroid niche at the morphological level. This study employed old-school techniques such as assessing the expression of surface antigens at a single antigen resolution using immunogold-labelling visualisation combined with a high-resolution scanning electron microscope. The emerging field of volumetric electron microscopy technology not only dissects the subcellular components of the erythroid niche, but also the intercellular communication from a morphological perspective such as a distal pinez interaction. Three-dimensional reconstruction of 250 serial micrographs provided novel insights of the erythroid niche with a 3-dimensional perspective, including inter-organelle interactions. State-of-the-art multi-spectral flow cytometric analyses enabled assessment of erythroid mitochondrial dynamics. Utilising classical MitoTracker dyes and novel synthetic fluorescent probes, a new intercellular process in the EBIs was also observed with rapid live cell imaging and high-resolution confocal imaging. This study also led to the proposal of a synaptic interaction in the EBIs driven by a pro-inflammatory cytokine, interferon gamma. Collectively, this study bridges the current technology available to understanding the erythroid niche and provides insights in which the erythroid niche can regulate erythropoiesis

Hold, delete, suppress : a study of press censorship in occupied Japan

During the Military Occupation of Japan by the United States from 1945-1952, all forms of media and expression were subject to a strict censorship regime carried out by Allied GHQ. Despite having arrived with a mission to democratise Japan, the US felt the need to suppress speech and communication that was potentially harmful to the overall success of the Occupation. Fearful of the Japanese press’s power to influence public opinion, Occupation authorities sought to control the press by introducing codes of behaviour and drawing boundaries of acceptable discourse. This paper uses the experiences of the Japanese press and the content of newspaper articles that were censored by Occupation authorities as a lens through which to view the growing fears of the US throughout the Occupation. In doing so, this paper wishes to challenge the widely-held notion that Occupation censorship was a tool of power and control over the occupied Japanese. As evidenced by the ways in which various Japanese newspapers engaged with the censorship apparatus, the use of censorship created arenas for the press to contest GHQ’s authority; ultimately signifying the limits of the Americans’ powers as an occupying force.Bachelor of Arts in Histor

Elucidating the Roles of Fenton Reactants in Drug-Treated Cells using a Selective Rhodamine-Thiophenol Fluorogenic Sensor

While Fenton chemistry has long been known to play a role in inducing cellular stress, there has been recent renewed interest in understanding its roles in health and disease. Here we describe a fluorogenic probe, RTFt1, which applies both chelation and recognition strategies to sense the Fenton reactants, Fe(II) and H2O2. RTFt1 undergoes a 200-fold increase in red fluorescence emission in the presence of both Fe(II) and H2O2. After confirming the suitability of this new probe in cellular models, we demon-strated its utility in sensing the Fenton chemistry that accompanies ferroptosis and cisplatin-induced cytotoxicity. We found that levels of the Fenton reactants increased when cells were treated with cisplatin or co-treated with cisplatin and tubastatin A. This points to a role for Fenton chemistry in the cytotoxic effects of these treatments. We expect that RTFt1 will be able to provide a deeper understanding of Fenton reactants more broadly in biological systems

Can flow cytometric measurements of reactive oxygen species levels determine minimal inhibitory concentrations and antibiotic susceptibility testing for Acinetobacter baumannii?

Current antimicrobial susceptibility testing (AST) requires 16-24 hours, delaying initiation of appropriate antibiotics. Hence, there is a need for rapid AST. This study aims to develop and evaluate the feasibility of a rapid flow cytometric AST assay to determine minimum inhibitory concentration (MIC) for carbapenem-resistant Acinetobacter baumannii (CRAB). Antibiotic exposure causes increased intracellular reactive oxygen species (ROS) in bacteria. We hypothesized that ROS can be used as a marker to determine MIC. We assessed three CRAB clinical isolates across fifteen antibiotics at various concentrations in a customized 96-well microtiter plate. The antibiotics assessed include amikacin, beta-lactams (ampicillin/sulbactam, aztreonam, cefepime, ceftolozane/tazobactam, doripenem, imipenem, meropenem, and piperacillin/tazobactam), levofloxacin, polymyxin B, rifampicin, trimethoprim/sulfamethoxazole, and tetracyclines (tigecycline and minocycline). These clinical CRAB isolates were assessed for ROS after antibiotic treatment. Increased ROS levels indicated by increased RedoxSensorTM Green (RSG) fluorescence intensity was assessed using flow cytometry (FCM). MIC was set as the lowest antibiotic concentration that gives a ≥1.5-fold increase in mode RSG fluorescence intensity (MICRSG). Accuracy of MICRSG was determined by comparing against microtiter broth dilution method performed under CLSI guidelines. ROS was deemed accurate in determining the MICs for β-lactams (83.3% accuracy) and trimethoprim/sulfamethoxazole (100% accuracy). In contrast, ROS is less accurate in determining MICs for levofloxacin (33.3% accuracy), rifampicin (0% accuracy), amikacin (33.3% accuracy), and tetracyclines (33.3% accuracy). Collectively, this study described an FCM-AST assay to determine antibiotic susceptibility of CRAB isolates within 5 hours, reducing turnaround time up to 19 hours

A super-resolution CMOS image sensor for bio-microfluidic imaging

A super-resolution CMOS image sensor is introduced in this paper for bio-microfluidic imaging. Compared to the traditional scientific CCD or CMOS image sensor, our design achieves the balance between high-sensitivity and high-resolution from system design perspective with the use of single-frame super-resolution. Moreover, the column-parallel image sensor architecture with correlated-double-sampling is deployed for high-speed and low-noise readout. The chip is designed in standard 0.18μm CMOS mixed-signal process with area of 2.5mm×5.0mm, 128×128 pixel-array and speed of 1750 frames/s. The resolution is improved by 4X by on-chip super-resolution algorithm while large pixel (10μm×10μm) is employed in image sensor for high-sensitivity.Accepted versio

Studies of the labile lead pool using a rhodamine-based fluorescent probe

Lead is a heavy metal which has long been known to have toxic effects on the body. However, much remains to be learnt about the labile lead pool and cellular uptake of lead. We report here RPb1 that undergoes a 100-fold increase in fluorescence emission in the presence of Pb2+, and which can be applied to study the labile lead pool within cells. We demonstrate the capacity of RPb1 for investigating labile lead pool in DLD-1 cells and changes in labile lead during differentiation of K562 cells