The Gß-like protein Bcgbl1 regulates development and pathogenicity of the gray mold Botrytis cinerea via modulating two MAP kinase signaling pathways.

The fungal Gß-like protein has been reported to be involved in a variety of biological processes, such as mycelial growth, differentiation, conidiation, stress responses and infection. However, molecular mechanisms of the Gß-like protein in regulating fungal development and pathogenicity are largely unknown. Here, we show that the Gß-like protein gene Bcgbl1 in the gray mold fungus Botrytis cinerea plays a pivotal role in development and pathogenicity by regulating the mitogen-activated protein (MAP) kinases signaling pathways. The Bcgbl1 deletion mutants were defective in mycelial growth, sclerotial formation, conidiation, macroconidial morphogenesis, plant adhesion, and formation of infection cushions and appressorium-like structures, resulting in a complete loss of pathogenicity. Bcgbl1 interacted with BcSte50, the adapter protein of the cascade of MAP kinase (MAPK). Bcgbl1 mutants had reduced phosphorylation levels of two MAPKs, namely Bmp1 and Bmp3, thereby reducing infection. However, deletion of Bcgbl1 did not affect the intracellular cAMP level, and exogenous cAMP could not restore the defects. Moreover, Bcgbl1 mutants exhibited defects in cell wall integrity and oxidative stress tolerance. Transcriptional profiling revealed that Bcgbl1 plays a global role in regulation of gene expression upon hydrophobic surface induction. We further uncovered that three target genes encoding the hydrophobic surface binding proteins (HsbAs) contributed to the adhesion and virulence of B. cinerea. Overall, these findings suggest that Bcgbl1 had multiple functions and provided new insights for deciphering the Bcgbl1-mediated network for regulating development and pathogenicity of B. cinerea.

Sirt5-mediated lysine desuccinylation regulates oxidative stress adaptation in Magnaporthe oryzae during host intracellular infection.

Plant pathogenic fungi elaborate numerous detoxification strategies to suppress host reactive oxygen species (ROS), but their coordination is not well-understood. Here, we show that Sirt5-mediated protein desuccinylation in Magnaporthe oryzae is central to host ROS detoxification. SIRT5 encodes a desuccinylase important for virulence via adaptation to host oxidative stress. Quantitative proteomics analysis identified a large number of succinylated proteins targeted by Sirt5, most of which were mitochondrial proteins involved in oxidative phosphorylation, TCA cycle, and fatty acid oxidation. Deletion of SIRT5 resulted in hypersuccinylation of detoxification-related enzymes, and significant reduction in NADPH : NADP+ and GSH : GSSG ratios, disrupting redox balance and impeding invasive growth. Sirt5 desuccinylated thioredoxin Trx2 and glutathione peroxidase Hyr1 to activate their enzyme activity, likely by affecting proper folding. Altogether, this work demonstrates the importance of Sirt5-mediated desuccinylation in controlling fungal process required for detoxifying host ROS during M. oryzae infection.

The evolution of preexisting primary immune thrombocytopenia after COVID-19 onset: A nationally representative, prospective, multicentre, observational study.

The symptoms in patients with primary immune thrombocytopenia (ITP) after COVID-19 onset remain largely unclear. The aim of this study was to describe the platelet count fluctuations in ITP patients following the diagnosis of COVID-19. A prospective multicentre observational study was conducted from December 15th, 2022, to January 31st, 2023 in 39 general hospitals across China. Patients with preexisting primary ITP who were newly diagnosed with COVID-19 were enrolled. A total of 1216 ITP patients with newly-diagnosed COVID-19 were enrolled. 375 (30.8%) patients experienced ITP exacerbation within eight weeks after the diagnosis of COVID-19, and most exacerbation (266/375, 70.9%) developed in the first two weeks. Immunosuppressive therapy for ITP and severe/critical COVID-19 infection were independent variables associated with ITP exacerbation. Overall the platelet count had a transient increasing trend, and the platelet peak value occurred at two weeks after COVID-19 infection. Then, the platelet count decreased to the baseline level in the following weeks. The platelet count had a transient increasing trend in ITP patients following the diagnosis of COVID-19. ITP exacerbation only occurred in less than one-third of ITP patients. Nonimmunosuppressive therapy may have an advantage to prevent ITP exacerbation during COVID-19.

Role of Platelet/Lymphocyte, Neutrophil/Lymphocyte, and Interleukin-37/Interleukin-17 Ratios in the Occurrence and Treatment of Rheumatoid Arthritis.

This study was designed to investigate the correlation of neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), and interleukin (IL)-37/IL-17 ratio with the incidence/treatment of rheumatoid arthritis (RA). Firstly, fifty-eight patients with RA treated at the first affiliated hospital of Xinjiang Medical University from January 2018 to January 2019 were selected as the RA group; forty-nine healthy volunteers were enrolled in the control group. RA patients were treated with disease-modifying anti-rheumatic drugs (DMARDs). Next, the NLR, PLR, IL-37, IL-17 and 28-joint disease activity score using erythrocyte sedimentation rate (DAS28-ESR) were deleted in two groups. Subsequently, Spearman correlation analysis was adopted for the correlations of various indicators before and after treatment in two groups. According to the analysis results, the levels of NLR, PLR, IL-37, and IL-17 before treatment in the RA group were higher than those in the control group (P < .05), but the difference in the IL-37/IL-17 level between the two groups was not significant (P > .05). After treatment, NLR, PLR, and IL-37/IL-17 levels were significantly reduced in RA patients (P < .05). NLR and PLR were significantly positively correlated with DAS28-ESR, ESR and C-reactive protein (CRP), of which represented the disease activity of RA. NLP was strongly correlated with IL-37/IL-17. Collectively, NLR, PLR, IL-37, and IL-17 are closely related to the occurrence of RA. In addition, NLR and IL-37/IL-17 are more suitable than PLR in reflecting the therapeutic effect. Therefore, IL-37/IL-17 can be considered as a new indicator for reflecting the treatment effectiveness of RA.

Tacrolimus prevents complement-mediated Nod-like receptor family pyrin domain containing 3 (NLRP3) inflammasome activation and pyroptosis of mesenchymal stem cells from immune thrombocytopenia.

The abnormal immunomodulatory functions of mesenchymal stem cells (MSCs) have been implicated in the development of immune thrombocytopenia (ITP). Recent studies have suggested important effects of complement on immune cell function. However, whether complement modulates bone marrow MSCs function in ITP is poorly defined. Tacrolimus has recently been applied to the treatment of autoimmune diseases. Here, we explored whether impaired ITP-MSCs could be targeted by tacrolimus. Our results showed that the Nod-like receptor family pyrin domain containing 3 (NLRP3) inflammasome was activated in ITP MSCs with complement deposition (MSCs-C+ ) and initiated caspase-1-dependent pyroptosis. Transcriptome sequencing results showed abnormal fatty acid metabolism in MSCs-C+ . Enhanced fatty acid ß-oxidation and reactive oxygen species production activated the NLRP3 inflammasome. Adipocytes derived from MSCs-C+ secreted less adiponectin. Adiponectin promoted the differentiation of megakaryocytes and inhibited the destruction of platelets. Tacrolimus inhibited NLRP3 inflammasome activation and MSCs-C+ pyroptosis in vitro and in vivo. Tacrolimus plus danazol elicited a higher sustained response than danazol monotherapy in corticosteroid-resistant patients with ITP. Our findings demonstrate that the activation of the NLRP3 inflammasome in ITP MSCs mediated by complement could be inhibited by tacrolimus, which might be a potential new therapy for ITP.

Plasma-Membrane-Localized Transporter NREET1 is Responsible for Rare Earth Element Uptake in Hyperaccumulator Dicranopteris linearis.

Rare earth elements (REEs) are critical for numerous modern technologies, and demand is increasing globally; however, production steps are resource-intensive and environmentally damaging. Some plant species are able to hyperaccumulate REEs, and understanding the biology behind this phenomenon could play a pivotal role in developing more environmentally friendly REE recovery technologies. Here, we identified a REE transporter NRAMP REE Transporter 1 (NREET1) from the REE hyperaccumulator fern Dicranopteris linearis. Although NREET1 belongs to the natural resistance-associated macrophage protein (NRAMP) family, it shares a low similarity with other NRAMP members. When expressed in yeast, NREET1 exhibited REE transport capacity, but it could not transport divalent metals, such as zinc, nickel, manganese, or iron. NREET1 is mainly expressed in D. linearis roots and predominantly localized in the plasma membrane. Expression studies in Arabidopsis thaliana revealed that NREET1 functions as a transporter mediating REE uptake and transfer from root cell walls into the cytoplasm. Moreover, NREET1 has a higher affinity for transporting light REEs compared to heavy REEs, which is consistent to the preferential enrichment of light REEs in field-grown D. linearis. We therefore conclude that NREET1 may play an important role in the uptake and consequently hyperaccumulation of REEs in D. linearis. These findings lay the foundation for the use of synthetic biology techniques to design and produce sustainable, plant-based REE recovery systems.

Can the parkland grading scale predict the difficulty of laparoscopic cholecystectomy? A new approach to validation.

BACKGROUND: The Parkland Grading Scale (PGS) is an intraoperative grading scale to stratify gallbladder disease severity during laparoscopic cholecystectomy (LC). We evaluated the usefulness of the PGS in predicting the difficulty levels of LC procedures using a novel approach. METHODS: A total of 261 patients diagnosed with cholelithiasis and cholecystitis who underwent LC were assessed. The PGS and the surgical difficulty grading system were used to evaluate surgical procedures by reviewing the operation videos. Clinical baseline characteristics and post-treatment outcomes were also recorded. Differences between the five PGS grades in terms of surgical difficulty scores were analyzed using the Jonckheere-Terpstra test. The relationship between PGS grades and surgical difficulty scores was assessed using Spearman's Rank correlation. Finally, the linear trends between morbidity scores and PGS grades were evaluated using the Mantel-Haenszel test. RESULTS: There was a significant difference in the surgical difficulty scores for the five PGS grades (p < 0.001). In pairwise comparison, each grade (1-5) was significantly different from the others (p < 0.05) in terms of surgical difficulty, except Grade 2 vs. 3 (p = 0.07) and Grade 3 vs. 4 (p = 0.08). There was a significant correlation between PGS grades and surgical difficulty scores (rs = 0.681, p < 0.001). There was also a significant linear association between morbidity and PGS grades (p < 0.001). Spearman's R value was 0.176 (p = 0.004). CONCLUSION: The PGS can accurately assess the surgical difficulty level of LC. The precision and conciseness of the PGS make it suitable for use in future research.

Increased difficulty and complications of delayed laparoscopic cholecystectomy following percutaneous transhepatic gallbladder drainage in acute cholecystitis: a retrospective study.

BACKGROUND: Percutaneous transhepatic gallbladder drainage (PTGBD) is a relatively less invasive alternative treatment to cholecystostomy. However, the influence of the difficulty of delayed laparoscopic cholecystectomy (DLC) after PTGBD on clinical outcomes remains unknown. This study aimed to evaluate the clinical effects of DLC following PTGBD. METHODS: The clinical data of 113 patients diagnosed with moderate (grade II) acute cholecystitis according to the 2018 Tokyo Guidelines in the acute phase and who underwent DLC in our hospital from January 2018 to February 2022 were retrospectively collected and separated into two groups according to whether they received PTGBD treatment in the acute stage. The PTGBD group comprised 27 cases, and the no-PTGBD group included 86 cases. The TG18 difficulty score was used to evaluate every surgical procedure in the cases by reviewing the surgical videos. The clinical baseline characteristics and post-treatment outcomes were also evaluated. RESULTS: Both groups showed significant differences in length of postoperative stay, blood loss, operation time, and difficulty score. The PTGBD group showed a significantly longer postoperative stay and operation time, more blood loss, and a much higher difficulty score than the no-PTGBD group. Conversion rates did not differ. The morbidity rate in the PTGBD group was statistically higher. CONCLUSIONS: PTGBD is an efficient way to relieve the symptoms of acute cholecystitis. However, it may increase the difficulty and complications of DLC.

Achiral Au(I) Cyclic Trinuclear Complexes with High-Efficiency Circularly Polarized Near-Infrared TADF.

Realizing high photoluminescence quantum yield (PLQY) in the near-infrared (NIR) region is challenging and valuable for luminescent material, especially for thermally activated delay fluorescence (TADF) material. In this work, we report two achiral cyclic trinuclear Au(I) complexes, Au3 (4-Clpyrazolate)3 and Au3 (4-Brpyrazolate)3 (denoted as Cl-Au and Br-Au), obtained through the reaction of 4-chloro-1H-pyrazole and 4-bromo-1H-pyrazole with Au(I) salts, respectively. Both Cl-Au and Br-Au exhibit TADF with high PLQY (>70 %) in the NIR I (700-900 nm) (λmax = 720 nm) region, exceeding other NIR-TADF emitters in the solid state. Photophysical experiments and theoretical calculations confirmed the efficient NIR-TADF properties of Cl-Au and Br-Au were attributed to the small energy gap ΔE(S1-T2) (S = singlet, T = triplet) and the large spin-orbital coupling induced by ligand-to-metal-metal charge transfer of molecular aggregations. In addition, both complexes crystallize in the achiral Pna21 space group (mm2 point group) and are circularly polarized light (CPL) active with maxima luminescent dissymmetry factor |glum | of 3.4 × 10-3 (Cl-Au) and 2.7 × 10-3 (Br-Au) for their crystalline powder samples, respectively. By using Cl-Au as the emitting ink, 3D-printed luminescent logos are fabricated, which own anti-counterfeiting functions due to its CPL behavior dependent on the crystallinity.

MTA1-mediated RNA m6 A modification regulates autophagy and is required for infection of the rice blast fungus.

In eukaryotes, N6 -methyladenosine (m6 A) is abundant on mRNA, and plays key roles in the regulation of RNA function. However, the roles and regulatory mechanisms of m6 A in phytopathogenic fungi are still largely unknown. Combined with biochemical analysis, MeRIP-seq and RNA-seq methods, as well as biological analysis, we showed that Magnaporthe oryzae MTA1 gene is an orthologue of human METTL4, which is involved in m6 A modification and plays a critical role in autophagy for fungal infection. The Δmta1 mutant showed reduced virulence due to blockage of appressorial penetration and invasive growth. Moreover, the autophagy process was severely disordered in the mutant. MeRIP-seq identified 659 hypomethylated m6 A peaks covering 595 mRNAs in Δmta1 appressoria, 114 m6 A peaks was negatively related to mRNA abundance, including several ATG gene transcripts. Typically, the mRNA abundance of MoATG8 was also increased in the single m6 A site mutant ∆atg8/MoATG8A982C , leading to an autophagy disorder. Our findings reveal the functional importance of the m6 A methylation in infection of M. oryzae and provide novel insight into the regulatory mechanisms of plant pathogenic fungi.

The impact of COVID-19 pandemic on the treatment of acute appendicitis in China.

OBJECTIVE: This research aims to analyze the impact of the novel coronavirus pandemic on the hospital visits of patients with acute appendicitis. METHODS: The retrospective analysis was designed to look at the treatment of acute appendicitis in the Department of General Surgery in Beijing Jishuitan Hospital before and during the COVID-19 pandemic (2019-2020). Data was analyzed by the numbers of patients, sex, age, onset time, fever or not, laboratory examination, imaging test, and treatment. And we analyzed the differences between the "pre-COVID group" and "during-COVID group". RESULTS: Compared with the year 2019, the number of acute appendicitis patients has diminished substantially during the COVID-19 pandemic (2020), but the number elevated with the control of the pandemic. Even if we did not find the differences of the treatment before and during the pandemic (P = 0.932), the onset time to emergency was significantly longer (P < 0.001), and more patients had showed fever (P < 0.001) during the COVID-19 pandemic. And the total number of white blood cells and C reactive protein level were significantly higher in 2020 than those in 2019 (P = 0.006, 0.003). And the same result was found in patients with appendiceal fecalith (P = 0.047). CONCLUSION: During the pandemic of the new coronavirus pneumonia, the number of patients with acute appendix treatment dropped significantly, mainly because it took longer than before, and the condition was more severe. It can be seen that the new coronary pneumonia has a great impact on the patients' medical treatment behavior, and the active prevention and treatment of the new coronavirus pneumonia is currently an important and urgent issue.

Characteristics of ocular findings of patients with neuronal intranuclear inclusion disease.

PURPOSE: This study aimed to explore the ocular characteristics of neuronal intranuclear inclusion disease (NIID), caused by GGC repeat expansion in the NOTCH2NLC gene, combined with the systemic clinical manifestations, and propose early diagnostic features of NIID. METHODS: Six patients (12 eyes) were enrolled in this study. In vivo corneal confocal microscopy (IVCCM), fundus photography, fundus autofluorescence (FAF) imaging, optical coherence tomography (OCT), full-field electroretinography (ERG), and electromyography were performed. RESULTS: The average corneal nerve fiber density (CNFD) was 6.83 ± 4.96 number/mm2, and the corneal nerve fiber length (CNFL) was 6.76 ± 1.96 mm/mm2. The nerves were looser and more curved in affected individuals. Dendritic cells were observed in patients with NIID. Chorioretinal atrophy, hyper-AF spots, and outer retinal abnormalities were observed during FAF imaging and OCT examinations. In full-field ERGs, the amplitudes of the a-wave and b-wave reduced or extinguished over time. The compound muscle action potential and motor nerve conduction velocity of the left common peroneal nerve decreased substantially. CONCLUSION: The findings of IVCCM and retinal changes should be included in the diagnostic criteria for NIID. Corneal confocal characteristics may precede the systemic neurological manifestations and provide a clinical basis for the early treatment and staging of the disease. ClincalTrials.gov. Identifier: ChiCTR21000500227.

Optical coherence tomography angiography for the detection and evaluation of ptic disc neovascularization: a retrospective, observational study.

BACKGROUND: To assess and characterize neovascularization of the optic disc (NVD) using optical coherence tomography angiography (OCTA) and different OCTA-based methods. METHODS: This retrospective, observational study included patients who were suspected of having early PDR with no presence of clinically apparent neovascularization (NV) bur were clinically diagnosed with proliferative diabetic retinopathy (PDR), or severe NPDR. Patients underwent standard clinical examinations and OCTA imaging using a 6 × 6 montage scan. Two trained graders identified NVD using different imaging systems (ultra-widefield-colour fundus photography (UWF-CFP), OCT, OCTA and fluorescein angiography (FA)). Moreover, morphological classification of NVD was performed. The detection and morphological classification of NVD by different OCTA-based methods (B-scan OCTA, En-face OCTA, VRI Angio and VRI Structure) were compared. RESULTS: A total of 169 eyes (126 eyes with PDR and 43 eyes with severe NPDR) of 123 participants were included in this study. The detection rate of NVD was 34.91% by UWF-CFP compared with 59.76% by OCT, 59.76% by OCTA, and 62.72% by FA. After excluding 2 cases with epiretinal membranes, the NVD diagnosis detected by OCT was used as the standard. Among 99 eyes diagnosed with NVD by OCT, B-scan OCTA detected NVD with a sensitivity of 97.98%, which was higher than that by en face OCTA (80.81%), VRI Angio (65.66%), and VRI Structure (61.62%) (all P < 0.05). According to its characteristics on OCTA, NVD was divided into four types (12 cases of type I, 6 cases of type II, 39 cases of type III, and 42 cases of type IV). For type I, B-scan OCTA exhibited a higher diagnostic sensitivity than other methods (P < 0.05). For types II and IV, there were no statistically significant differences in the sensitivity of various methods between the two groups (P > 0.05). CONCLUSION: OCTA and different OCTA-based methods are significant to the diagnosis of NVD, and the diagnostic accuracy of different detection methods may be related to different types of NVD.

Wide-field swept-source OCTA in the assessment of retinal microvasculature in early-stage diabetic retinopathy.

BACKGROUND: To perform a quantitative analysis of retinal microvasculature in patients with early-stage diabetic retinopathy (DR) using wide-field swept-source optical coherence tomography angiography (SS-OCTA).  METHODS: One hundred nineteen eyes of 119 patents (67 eyes with no DR and 52 eyes with mild-moderate nonproliferative diabetic retinopathy (NPDR)) were enrolled in this observational and cross-sectional cohort study, and an age-matched group consisting of 39 eyes of 39 non-diabetic subjects were set as the control. Each participant underwent a full ophthalmic examination, including wide-field SS-OCTA imaging. On OCTA scans (12 mm * 12 mm), the mean perfusion area (PA) and vessel density (VD) were independently measured in all 16 Early Treatment Diabetic Retinopathy Study (ETDRS) sectors. Linear regression analyses were conducted to evaluate the influences of PA. RESULTS: In the central ring, there were no significant differences in the average PA and VD among the groups. In the 3 mm radius, the PA and VD of the no DR and mild-moderate NPDR were significantly decreased compared with the control group in superior and inferior quadrants. In the wide-field scans (9 and 12 mm radius), there was no significant difference in average PA and VD between the groups in each sectors (p > 0.05). Regression analysis found that the effect of VD on PA was statistically different (b = 1.311, p < 0.001). CONCLUSION: Wide-field OCTA imaging is useful for evaluating peripheral capillary perfusion in eyes with early-stage DR. Decrease in PA and VD was greater in the S3 and I3 sectors, and reductions in PA and VD were uneven in wide-filed sectors (9 and 12 mm radius).

Decision-making changes for patients and medical personnel in the management of acute appendicitis during the COVID-19 pandemic.

BACKGROUND: Acute appendicitis is the most common cause of acute abdomen. During the pandemic, to contain the spread of COVID-19, there were some integral changes in the medical processes based on the pandemic prevention policy, especially regarding emergency surgery. This study was conducted to investigate whether this pandemic also impacted the decision-making for both patients and medical personnel along with the treatment outcomes. METHODS: Patients of age 18 years or older who were diagnosed clinically and radiologically with acute appendicitis between Jan 1, 2017, and Dec 31, 202,0 were reviewed. The data of 1991 cases were collected and used for this study. Two groups were formed, one group before and the other group after the outbreak. The gathered data included gender, age, appendiceal fecalith, outcomes of treatment, and long-term outcomes of non-operation (8 months follow-up). We also collected details of surgical cases from the above two groups. This data also included age, gender, appendiceal fecalith, fever, jaundice, length of onset before presenting to an emergency department (ED), anesthesia, surgery, white cell count, pathology, complications, and length of stay. We compared the above data respectively and analyzed the differences. RESULTS: Compared to the period before the outbreak, patient visits for acute appendicitis remarkably dropped (19.8%), but surgical cases showed no change (dropped by roughly 5%). There were significant differences (P < 0.05) in failure of non-operation(after the pandemic 8.31% vs. before pandemic 3.22%), interval appendectomy(after pandemic 6.29% vs. before pandemic 12.84%), recurrence(after pandemic 23.27% vs. before pandemic 14.46%), and outcomes of recurrence. There was a significant difference (P < 0.05) in anesthesia method, surgery way, and complications( before pandemic 4.15% vs. after pandemic9.89% P < 0.05) in patients who underwent the surgery. There was no statistical difference (P > 0.05) concerning age, gender, fever, jaundice, appendiceal fecalith, white cell count, and length of onset before presenting to the ED. CONCLUSION: The current pandemic prevention policy is very effective, but some decision-making processes of doctor-patient have changed in the context of COVID-19 pandemic, that further influenced some treatment outcomes and might lead to a potential economic burden. It is essential to address the undue concern of everyone and optimize the treatment process.

Iron status, fibroblast growth factor 23 and cardiovascular and kidney outcomes in chronic kidney disease.

Disordered iron and mineral homeostasis are interrelated complications of chronic kidney disease that may influence cardiovascular and kidney outcomes. In a prospective analysis of 3747 participants in the Chronic Renal Insufficiency Cohort Study, we investigated risks of mortality, heart failure, end-stage kidney disease (ESKD), and atherosclerotic cardiovascular disease according to iron status, and tested for mediation by C-terminal fibroblast growth factor 23 (FGF23), hemoglobin and parathyroid hormone. Study participants were agnostically categorized based on quartiles of transferrin saturation and ferritin as "Iron Replete" (27.1% of participants; referent group for all outcomes analyses), "Iron Deficiency" (11.1%), "Functional Iron Deficiency" (7.6%), "Mixed Iron Deficiency" (iron indices between the Iron Deficiency and Functional Iron Deficiency groups; 6.3%), "High Iron" (9.2%), or "Non-Classified" (the remaining 38.8% of participants). In multivariable-adjusted Cox models, Iron Deficiency independently associated with mortality (hazard ratio 1.28, 95% confidence interval 1.04-1.58) and heart failure (1.34, 1.05- 1.72). Mixed Iron Deficiency associated with mortality (1.61, 1.27-2.04) and ESKD (1.33, 1.02-1.73). High Iron associated with mortality (1.54, 1.24-1.91), heart failure (1.58, 1.21-2.05), and ESKD (1.41, 1.13-1.77). Functional Iron Deficiency did not significantly associate with any outcome, and no iron group significantly associated with atherosclerotic cardiovascular disease. Among the candidate mediators, FGF23 most significantly mediated the risks of mortality and heart failure conferred by Iron Deficiency. Thus, alterations in iron homeostasis associated with adverse cardiovascular and kidney outcomes in patients with chronic kidney disease.

Mineral bone disease in autosomal dominant polycystic kidney disease.

Mice with disruption of Pkd1 in osteoblasts demonstrate reduced bone mineral density, trabecular bone volume and cortical thickness. To date, the bone phenotype in adult patients with autosomal dominant polycystic kidney disease (ADPKD) with stage I and II chronic kidney disease has not been investigated. To examine this, we characterized biochemical markers of mineral metabolism, examined bone turnover and biology, and estimated risk of fracture in patients with ADPKD. Markers of mineral metabolism were measured in 944 patients with ADPKD and other causes of kidney disease. Histomorphometry and immunohistochemistry were compared on bone biopsies from 20 patients with ADPKD with a mean eGFR of 97 ml/min/1.73m2 and 17 healthy individuals. Furthermore, adults with end stage kidney disease (ESKD) initiating hemodialysis between 2002-2013 and estimated the risk of bone fracture associated with ADPKD as compared to other etiologies of kidney disease were examined. Intact fibroblast growth factor 23 was higher and total alkaline phosphatase lower in patients with compared to patients without ADPKD with chronic kidney disease. Compared to healthy individuals, patients with ADPKD demonstrated significantly lower osteoid volume/bone volume (0.61 vs. 1.21%) and bone formation rate/bone surface (0.012 vs. 0.026 µm3/µm2/day). ESKD due to ADPKD was not associated with a higher risk of fracture as compared to ESKD due to diabetes (age adjusted incidence rate ratio: 0.53 (95% confidence interval 0.31, 0.74) or compared to other etiologies of kidney disease. Thus, individuals with ADPKD have lower alkaline phosphatase, higher circulating intact fibroblast growth factor 23 and decreased bone formation rate. However, ADPKD is not associated with higher rates of bone fracture in ESKD.

Fibroblast Growth Factor 23 and Exercise Capacity in Heart Failure with Preserved Ejection Fraction.

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is characterized by left ventricular hypertrophy and decreased exercise capacity. Fibroblast growth factor 23 (FGF23), a hormone involved in phosphate, vitamin D, and iron homeostasis, is linked to left ventricular hypertrophy and HF. We measured c-terminal FGF23 (cFGF23) and intact FGF23 (iFGF23) levels and examined their associations with exercise capacity in patients with HFpEF. METHODS AND RESULTS: Using multivariable linear regression and linear mixed models, we studied the associations of cFGF23 and iFGF23 with baseline and mean weekly change over 24 weeks in peak oxygen consumption and 6-minute walk distance in individuals enrolled in the Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in HFpEF trial. Our study population included 172 individuals with available plasma for cFGF23 and iFGF23 measurements. Median (25th-75th percentile) baseline cFGF23 and iFGF23 levels were 208.7 RU/mL (132.1-379.5 RU/mL) and 90.3 pg/mL (68.6-128.5 pg/mL), respectively. After adjustment for cardiovascular disease and hematologic and kidney parameters, higher cFGF23 was independently associated with a lower peak oxygen consumption at baseline. Higher iFGF23 was independently associated with shorter 6-minute walk distance at baseline. No significant associations were appreciated with the longitudinal outcomes. CONCLUSIONS: In patients with HFpEF, higher FGF23 levels are independently associated with decreased exercise capacity at baseline.

Natural course of myopic traction maculopathy and factors influencing progression and visual acuity.

BACKGROUND: To describe the natural course of myopic traction maculopathy (MTM) and determine predictive factors for its progression and visual prognosis. METHODS: This retrospective observational study included 113 MTM patients (113 eyes). Best-corrected visual acuity (BCVA) measurements and optical coherence tomography findings were recorded. RESULTS: Over a mean follow-up of 38.2 ± 11.1 months, 49 of 113 eyes (43.4 %) progressed. The progression rate of outer schisis prominently located in the fovea or posterior staphyloma was significantly higher than that of outer schisis prominently located in paravascular areas (P = 0.0011). MTM with partial posterior vitreous detachment during the follow-up progressed more rapidly than MTM without (P = 0.0447). Patients with older age (> 65 years), without domed-shaped macula and with defects in the ellipsoid zone (EZ) had worse BCVA at the last visit (P = 0.0416, P = 0.0494and P = 0.0130). Multiple linear regression analysis showed that BCVA and defects in the EZ at baseline were significantly associated with the final BCVA (P < 0.0001 and P = < 0.0001, respectively). CONCLUSIONS: MTM has a high possibility for progression. Outer schisis located predominantly in the fovea or posterior staphyloma or with partial posterior vitreous detachment exhibits rapid progression. The integrity of the EZ is related to visual prognosis.

Association of different Candida species with catheter-related candidemia, and the potential antifungal treatments against their adhesion properties and biofilm-forming capabilities.

BACKGROUND: To compare the adhesion properties and biofilm-forming capabilities of 27 Candida isolates obtained from catheter-related candidemia patients and to evaluate the inhibitory effects of antifungal agents on different Candida species. MATERIAL AND METHODS: Seven C. albicans, six C. parapsilosis, five C. guilliermondii, five C. tropicalis, and four C. glabrata clinical isolates were investigated. We quantified the adherence of these Candida species by flow cytometric method and evaluated the formation of biofilms by XTT reduction and crystal violet methods. Actions of micafungin (MF), fluconazole (FZ), and N-acetylcysteine (NAC) on the adhesion and biofilm formation of different Candida species were determined. RESULTS: Non-albicans Candida species were demonstrated to have stronger adhesion abilities compared with C. albicans. The biofilm-forming capabilities of different Candida species were varied considerably, and the degree of biofilm formation might be affected by different assay approaches. Interestingly, C. parapsilosis displayed the highest biofilm formation abilities, while C. glabrata exhibited the lowest total biomass and metabolic activity. Furthermore, the inhibitory activities of MF, FZ, and NAC on fungal adhesion and biofilm formation were evaluated, and the results indicated that MF could reduce the adhesion ability and biofilm metabolism more significantly (p < 0.05), and its antifungal activity was elevated in a dose-dependent manner. CONCLUSION: Non-albicans Candida species, especially C. guilliermondii, C. tropicalis, and C. parapsilosis, exhibited higher adhesion ability in catheter-related candidemia patients. However, these Candida species had varied biofilm-forming capabilities. MF tended to have stronger inhibitory effects against both adhesion and biofilm formation of different Candida species.