To compare the incidence of anterior capsular tears after femtosecond laser-assisted cataract surgery (FLACS) versus phacoemulsification cataract surgery (PCS) and to assess the ultrastructural ...features of anterior capsulotomy specimens (FLACS and PCS) using electron microscopy.
Prospective, multicenter, comparative cohort case series.
Consecutive patients undergoing FLACS or PCS.
A prospective cohort study of all patients (n = 1626) undergoing FLACS or PCS by 2 surgeons from centers A and B was undertaken to compare the incidence of anterior capsule tears. Anterior lens capsules were collected by 4 surgeons from centers A, B, C, and D using 3 different commercially available femtosecond platforms, each with latest version upgrades. Lens capsule tissue was prepared for scanning electron microscopy (SEM) using a total of 10 samples for patients undergoing PCS, and 40 samples for patients undergoing FLACS.
Incidence of anterior capsule tear and comparative ultrastructural features of capsular samples from both PCS and FLACS cases.
There was a significantly increased rate of anterior capsule tears in the FLACS group (15/804 1.87%) when compared with the PCS group (1/822 0.12%; P = 0.0002, Fisher exact test). In 7 cases, the anterior capsule tear extended to the posterior capsule. Because all cases had occurred in complete capsulotomy, the integrity of the anterior capsule was questioned in the FLACS group. Subsequent SEM sampling showed irregularity at the capsule margin, as well as multiple apparently misplaced laser pits in normal parts of the tissue. Aberrant pits were approximately 2 to 4 μm apart and occurred at a range of 10 to 100 μm radially from the capsule edge.
Laser anterior capsulotomy integrity seems to be compromised by postage-stamp perforations and additional aberrant pulses, possibly because of fixational eye movements. This can lead to an increased rate of anterior capsule tears, and extra care should be taken during surgery after femtosecond laser pretreatment has been performed. A learning curve may account for some of the increased complication rate with FLACS. However, the SEM features raise safety concerns for capsular integrity after FLACS and warrant further investigation.
Hypercapnia occurs when the partial pressure of carbon dioxide (CO
) in the blood exceeds 45 mmHg. Hypercapnia is associated with several lung pathologies and is transcriptionally linked to ...suppression of immune and inflammatory signalling through poorly understood mechanisms. Here we propose Orphan Nuclear Receptor Family 4A (NR4A) family members NR4A2 and NR4A3 as potential transcriptional regulators of the cellular response to hypercapnia in monocytes. Using a THP-1 monocyte model, we investigated the sensitivity of NR4A family members to CO
and the impact of depleting NR4A2 and NR4A3 on the monocyte response to buffered hypercapnia (10% CO
) using RNA-sequencing. We observed that NR4A2 and NR4A3 are CO
-sensitive transcription factors and that depletion of NR4A2 and NR4A3 led to reduced CO
-sensitivity of mitochondrial and heat shock protein (Hsp)-related genes, respectively. Several CO
-sensitive genes were, however, refractory to depletion of NR4A2 and NR4A3, indicating that NR4As regulate certain elements of the cellular response to buffered hypercapnia but that other transcription factors also contribute. Bioinformatic analysis of conserved CO
-sensitive genes implicated several novel putative CO
-sensitive transcription factors, of which the ETS Proto-Oncogene 1 Transcription Factor (ETS-1) was validated to show increased nuclear expression in buffered hypercapnia. These data give significant insights into the understanding of immune responses in patients experiencing hypercapnia.
Abstract
There is uncertainty regarding carotenoid intake recommendations, because positive and negative health effects have been found or are correlated with carotenoid intake and tissue levels ...(including blood, adipose tissue, and the macula), depending on the type of study (epidemiological vs intervention), the dose (physiological vs supraphysiological) and the matrix (foods vs supplements, isolated or used in combination). All these factors, combined with interindividual response variations (eg, depending on age, sex, disease state, genetic makeup), make the relationship between carotenoid intake and their blood/tissue concentrations often unclear and highly variable. Although blood total carotenoid concentrations <1000 nmol/L have been related to increased chronic disease risk, no dietary reference intakes (DRIs) exist. Although high total plasma/serum carotenoid concentrations of up to 7500 nmol/L are achievable after supplementation, a plateauing effect for higher doses and prolonged intake is apparent. In this review and position paper, the current knowledge on carotenoids in serum/plasma and tissues and their relationship to dietary intake and health status is summarized with the aim of proposing suggestions for a “normal,” safe, and desirable range of concentrations that presumably are beneficial for health. Existing recommendations are likewise evaluated and practical dietary suggestions are included.
The nuclear receptor sub-family 4 group A (NR4A) family are early response genes that encode proteins that are activated in several tissues/cells in response to a variety of stressors. The NR4A ...family comprises
,
and
of which
and
are under researched and less understood, particularly in the context of immune cells. NR4A expression is associated with multiple diseases e.g. arthritis and atherosclerosis and the development of NR4A-targetting molecules as therapeutics is a current focus in this research field. Here, we use a combination of RNA-sequencing coupled with strategic bioinformatic analysis to investigate the down-stream effects of
and
in monocytes and dissect their common and distinct signalling roles. Our data reveals that
and
depletion has a robust and broad-reaching effect on transcription in both the unstimulated state and in the presence of LPS. Interestingly, many of the genes affected were present in both the unstimulated and stimulated states revealing a previously unappreciated role for the NR4As in unstimulated cells. Strategic clustering and bioinformatic analysis identified both distinct and common transcriptional roles for
and
in monocytes.
notably was linked by both bioinformatic clustering analysis and transcription factor interactome analysis to pathways associated with antigen presentation and regulation of MHC genes.
in contrast was more closely linked to pathways associated with viral response. Functional studies further support our data analysis pointing towards preferential/selective roles for
in the regulation of antigen processing with common roles for
and
evident with respect to cell migration. Taken together this study provides novel mechanistic insights into the role of the enigmatic nuclear receptors NR4A2 and NR4A3 in monocytes.
CO2 is produced during aerobic respiration. Normally, levels of CO2 in the blood are tightly regulated but pCO2 can rise (hypercapnia, pCO2 > 45 mmHg) in patients with lung diseases, for example, ...chronic obstructive pulmonary disease (COPD). Hypercapnia is a risk factor in COPD but may be of benefit in the context of destructive inflammation. The effects of CO2 per se, on transcription, independent of pH change are poorly understood and warrant further investigation. Here we elucidate the influence of hypercapnia on monocytes and macrophages through integration of state‐of‐the‐art RNA‐sequencing, metabolic and metabolomic approaches. THP‐1 monocytes and interleukin 4–polarized primary murine macrophages were exposed to 5% CO2 versus 10% CO2 for up to 24 h in pH‐buffered conditions. In hypercapnia, we identified around 370 differentially expressed genes (DEGs) under basal and about 1889 DEGs under lipopolysaccharide‐stimulated conditions in monocytes. Transcripts relating to both mitochondrial and nuclear‐encoded gene expression were enhanced in hypercapnia in basal and lipopolysaccharide‐stimulated cells. Mitochondrial DNA content was not enhanced, but acylcarnitine species and genes associated with fatty acid metabolism were increased in hypercapnia. Primary macrophages exposed to hypercapnia also increased activation of genes associated with fatty acid metabolism and reduced activation of genes associated with glycolysis. Thus, hypercapnia elicits metabolic shifts in lipid metabolism in monocytes and macrophages under pH‐buffered conditions. These data indicate that CO2 is an important modulator of monocyte transcription that can influence immunometabolic signaling in immune cells in hypercapnia. These immunometabolic insights may be of benefit in the treatment of patients experiencing hypercapnia.
This study investigates the effect of elevated CO2 (hypercapnia) on monocyte and macrophage transcription. Our data suggest that CO2 is a cellular stressor that shifts the immunometabolic phenotype of monocytes and macrophages toward increased fatty acid metabolism.
Fungal prosthetic joint infection (PJI) is rare, with Candida species being the most frequently reported pathogen in the medical literature. The risk of relapse following delayed reimplantation ...arthroplasty for candidal PJI is unknown. We describe 4 new cases and summarize 6 previously reported cases of candidal PJI treated with delayed reimplantation arthroplasty. Ninety percent of the patients received antifungal therapy. Eight patients received amphotericin B either alone or in combination with other antifungals. One patient received fluconazole alone. The median duration of time from resection arthroplasty to reimplantation for total hip and total knee arthroplasties was 8.6 and 2.3 months, respectively. Eight patients did not have relapse of candidal PJI following delayed reimplantation arthroplasty after a median duration of follow-up of 50.7 months (range, 2-73 months). Candidal PJI can be successfully treated with delayed reimplantation arthroplasty after receipt appropriate antifungal therapy.
We previously identified that the concentration of zeaxanthin in some commercially available carotenoid supplements did not agree with the product's label claim. The conclusion of this previous work ...was that more quality assurance was needed to guarantee concordance between actual and declared concentrations of these nutrients i.e., lutein (L) zeaxanthin (Z) and
-zeaxanthin (MZ) in commercially available supplements. Since this publication, we performed further analyses using different commercially available macular carotenoid supplements. Three capsules from one batch of eight products were analysed at two different time points. The results have been alarming. All of the powder filled products (
= 3) analysed failed to comply with their label claim (L: 19-74%; Z: 57-73%; MZ: 83-97%); however, the oil filled soft gel products (
= 5) met or were above their label claim (L: 98-122%; Z: 117-162%; MZ: 97-319%). We also identified that the carotenoid content of the oil filled capsules were stable over time (e.g., L average percentage change: -1.7%), but the powder filled supplements degraded over time (e.g., L average percentage change: -17.2%). These data are consistent with our previous work, and emphasize the importance of using carotenoid interventions in oil based formulas rather than powder filled formulas.
Humoral and cell-mediated immune responses are important in protection against measles. Non-response to vaccination has been associated with specific HLA-DR and HLA-DQ alleles; however, little is ...known about the relative importance of these alleles in the cellular immune response induced by measles virus vaccine. To investigate the role of HLA-DR/DQ class II restriction, a small pilot study was conducted. Lymphoproliferation assays using class II DR and DQ-specific monoclonal antibodies (MoAb) were performed at one week and two weeks post immunization with MMRII vaccine. The mean stimulation index (SI) was 4.4 and 5.3 at one and two weeks with reductions in SI of 47.6% and 70.2%, respectively, following the addition of DR-specific MoAb (p<0.001). These results clearly show that a significant proportion of the cell-mediated immune response to measles virus vaccine, as measured by SI, is HLA-DR restricted.
The macular carotenoids (i.e., lutein (L), zeaxanthin (Z) and
-zeaxanthin (MZ)) exhibit anti-inflammatory, antioxidant and optical properties that are believed to support human health and function. ...Studying the accumulation and distribution of these nutrients in tissues and organs, in addition to the eye, is an important step in understanding how these nutrients might support global human function and health (e.g., heart and brain). Chicken is an appropriate animal model with which to study the accumulation of these carotenoids in organs, as the relevant transport molecules and carotenoid binding proteins for L, Z and MZ are present in both humans and chickens. In this experiment, a sample of 3 chickens that were supplemented with L and MZ diacetate (active group) and a sample of 3 chickens that received a standard diet (control group) were analysed. Both groups were analysed for L, Z and MZ concentrations in the brain, eyes, heart, lung, duodenum/pancreas, jejunum/ileum, kidney and breast tissue. L, Z and MZ were identified in all the organs/tissues analysed from the active group. L and Z were identified in all of the organs/tissues analysed from the control group; while, MZ was identified in the eyes of these animals only. The discovery that MZ is accumulated in the tissues and organs of chickens supplemented with this carotenoid is important, given that it is known that a combination of L, Z and MZ exhibits superior antioxidant capacity when compared to any of these carotenoids in isolation.
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