Young Type Research Articles

Determinants of Knowledge, Attitudes, and Practices among Young Adults Type 2 Diabetes Patients in Selected Tertiary Hospitals in Shandong Province, China

Objective: The purpose of this study is to understand the current situation of knowledge, attitude, and practice of self-management in young patients with type 2 diabetes mellitus (T2DM) and to explore the relationship between general conditions (personal, social, and environment, clinical factors) and their knowledge, attitude, and practices (KAP) of diabetes self-management, This aims to provide patients with high-quality nursing care management and services, as well as to provide relevant recommendations for effective self-management. Methods: This study is a descriptive correlational study that used the purposive sampling method to investigate 359 patients with T2DM aged 18–25 years in four designated tertiary hospitals in Shandong Province. Results: Knowledge of self-management was correlated with sex, age, education level, occupation and work situation, monthly household income, medical payment method, family and friend support, frequency of diabetes health education, and diabetes complications. The attitude subscale was correlated with sex, age, education level, work situation, and family and friend support. The practice subscale was associated with age, education level, work situation, family and friend support, frequency of diabetes health education, and HbA1c values. Conclusion: Young adults aged 18–25 with T2DM have positive attitudes towards diabetes self-management, but there are still deficiencies in knowledge acquisition and behavioral practice. The KAP of self-management of diabetes is influenced by personal factors such as sex, age, and education level, and socio-environmental factors such as family income and family or friends’ social support. Additionally, clinical factors such as complications and HbA1c values significantly impacted the patient’s disease self-management ability.

Diabetic kidney disease screening status and related factors: a cross-sectional study of patients with type 2 diabetes in six provinces in China

ObjectiveTo understand the awareness and practice of diabetic kidney disease (DKD) or nephropathy screening among community-based patients with type 2 diabetes in six provinces and cities in China, and to analyse the related factors affecting screening practices.MethodsFrom December 2021 to March 2022, a cross-sectional survey was conducted using a structured questionnaire in 6230 patients with type 2 diabetes aged 18 years and older. The content of the questionnaire includes three parts: the general situation of diabetic patients (gender, age, ethnicity, marriage, education, occupation, etc.), DKD screening practices, and the evaluation of DKD screening services.Results89.70% of the patients had their fasting blood glucose measured every six months, 21.12% of the patients had their glycosylated hemoglobin measured every six months, and only 13.11% and 9.34% of the patients had a urine protein-creatinine ratio test and estimated glomerular filtration rate test every 12 months. The proportions of glycosylated hemoglobin, urine protein-creatinine ratio, and estimated glomerular filtration rate were relatively high in young, northern, highly educated, and long-duration type 2 diabetic patients.ConclusionThe results of this survey found that the proportion of urine protein-creatinine ratio testing, estimated glomerular filtration rate testing, and glycosylated hemoglobin testing in Chinese patients with type 2 diabetes was very low. Patients with type 2 diabetes in rural areas, southern areas, with low education level, and short course of disease have lower detection rates for DKD, and hence lower rates of prevention and treatment.

Effect of mutation at c.493T>C locus of transcription factor HNF1α gene on its protein level.

Hepatocyte nuclear factor 1α (HNF1α) is a transcription factor that is crucial for the regulation to maintain the function of pancreatic β-cell, hepatic lipid metabolism, and other processes. Mature-onset diabetes of the young type 3 is a monogenic form of diabetes caused by HNF1α mutations. Although several mutation sites have been reported, the specific mechanisms remain unclear, such hot-spot mutation as the P291fsinsC mutation and the P112L mutation and so on. In preliminary studies, we discovered one MODY3 patient carrying a mutation at the c.493T>C locus of the HNF1α gene. In this study, we analyzed the pathogenic of the mutation sites by using the Mutation Surveyor software and constructed the eukaryotic expression plasmids of the wild-type and mutant type of HNF1α to detect variations in the expression levels and stability of HNF1α protein by using Western blot. The analyses of the Mutation Surveyor software showed that the c.493T>C site mutation may be pathogenic gene and the results of Western blot showed that both the amount and stability of HNF1α protein expressed by the mutation type plasmid were reduced significantly compared to those by the wild type plasmid (P<0.05). This study suggests that the c.493T>C (p.Trp165Arg) mutation dramatically impacts HNF1α expression, which might be responsible for the development of the disease and offers fresh perspectives for the following in-depth exploration of MODY3's molecular pathogenic process.

Effects of Intranasal Dantrolene Nanoparticles on Brain Concentration and Behavior in PS19 Tau Transgenic Mice.

Repurposing dantrolene to treat Alzheimer's disease has been shown to be effective in amyloid transgenic mouse models but has not been examined in a model of tauopathy. The effects of a nanoparticle intranasal formulation, the Eagle Research Formulation of Ryanodex (ERFR), in young adult and aged wild type and PS19 tau transgenic mice was investigated. The bioavailability of intranasal ERFR was measured in 2 and 9-11-month-old C57BL/6J mice. Blood and brain samples were collected 20 minutes after a single ERFR dose, and the plasma and brain concentrations were analyzed. Baseline behavior was assessed in untreated PS19 tau transgenic mice at 6 and 9 months of age. PS19 mice were treated with intranasal ERFR, with or without acrolein (to potentiate cognitive dysfunction), for 3 months, beginning at 2 months of age. Animal behavior was examined, including cognition (cued and contextual fear conditioning, y-maze), motor function (rotarod), and olfaction (buried food test). The dantrolene concentration in the blood and brain decreased with age, with the decrease greater in the blood resulting in a higher brain to blood concentration ratio. The behavioral assays showed no significant changes in cognition, olfaction, or motor function in the PS19 mice compared to controls after chronic treatment with intranasal ERFR, even with acrolein. Our studies suggest the intranasal administration of ERFR has higher concentrations in the brain than the blood in aged mice and has no serious systemic side effects with chronic use in PS19 mice.

Generation and characterization of an induced pluripotent stem cell (iPSC) line SDQLCHi063-A from peripheral blood mononuclear cells of a patient with Maturity-onset diabetes of the young type 2 carrying GCK exon 1 deletion

Maturity-onset diabetes of the young type 2 (MODY2) is an autosomal dominant disorder caused by mutations in the GCK gene. It is characterized by a non-progressive slight increase in glycosylated hemoglobin (HbA1c), and mildly raised fasting glucose. Here, we generated an induced pluripotent stem cell line SDQLCHi063-A from a five-year-old boy with MODY2 carrying exon 1 deletion of the GCK gene (OMIM*138079). The iPSC line carries original gene mutation, expresses pluripotency markers, has normal karyotype and differentiated spontaneously in the three germ layers.

Metabolic control level and glucose variability in adolescents with type 1 diabetes during low and high-intensity exercise.

The main purpose of this study was to characterize the determinants of metabolic changes in young type 1 diabetes (T1DM) and to determine glycemic variability during low and high-intensity exercise. 20 young male T1DM patients were divided into two subgroups characterized by levels of glycated hemoglobin (HbA1c): HbA1c<7.3% (better HbA1c subgroup, n=10) and with levels HbA1c>7.3% (worse HbA1c subgroup, n=10). All participants performed a maximal oxygen uptake test and two efforts of various intensities (45 minutes of aerobic exercise and 30 minutes of mixed aerobic-anaerobic intensity exercise). Continuous glucose monitors (CGM) were used to control the glucose concentration. Changes in biomarkers describing the metabolic response were similar in both groups. A comparison of applied efforts exhibited that maximal capacity effort resulted in the highest values of blood glucose (BG) at the end (150.9-160.6 mg/dl) and 1 hour after the exercise (140.2-161.3 mg/dl). BG concentration before, during, 1 hour, and 24 hours after each exercise was insignificantly higher in the worse Hb1Ac group. HbA1c levels are insufficient to confirm whether the applied effort is performed in acceptable glycemic values. The CGM monitors allow for precise control of BG variations and accurate planning of physical activity by adjusting the insulin and carbohydrate consumption dose.

Quality of life in young patients with acute type a aortic dissection in China: comparison with Marfan syndrome and non-Marfan syndrome

BackgroundThere is a paucity of Chinese studies evaluating the quality of life (QoL) in young acute type A aortic dissection (AAAD) patients with Marfan syndrome.MethodsYoung adult AAAD patients (younger than 45 years old) underwent surgical treatment at our institution from January 2017 to December 2020 were consecutive enrolled. The hospital survivors completed 1 year of follow up. Patients were divided into two groups according to the presence or absence of Marfan syndrome (MFS). A 1:1 propensity score matching (PSM) with a caliper 0.2 was conducted to balance potential bias in baseline. The follow-up data were analyzed primarily for change in quality of life and anxiety status.ResultsAfter PSM, 32 comparable pairs were matched. The baseline data were comparable and postoperative complications were similar between groups. In terms of SF-36 scale, the role physical, bodily pain, role emotional and mental health subscales were no significantly improved in MFS patients over time. At 1 year after discharged, the subscale of mental health and bodily pain were significantly lower in the MFS group than in the non-MFS group. In terms of HADS assessments, the level of anxiety in MFS patients was significantly higher than in non-MFS patients at 1 year after discharged.ConclusionsThe QoL in young AAAD patients with MFS is lower than those without MFS after surgery. This may be associated with the uncontrollable persistent chronic pain and the uncertainty and concerns for the disease’s progression.

The first case of hyperosmolar diabetic ketoacidosis in a patient diagnosed with MODY 5 (maturity-onset diabetes of the young type 5) and 17q12 microdeletion syndrome.

The first case of hyperosmolar diabetic ketoacidosis in a patient diagnosed with MODY 5 (maturity-onset diabetes of the young type 5) and 17q12 microdeletion syndrome.

Assessment of pathogenicity and functional characterization of APPL1 gene mutations in diabetic patients.

Adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 1 (APPL1) plays a crucial role in regulating insulin signaling and glucose metabolism. Mutations in the APPL1 gene have been associated with the development of maturity-onset diabetes of the young type 14 (MODY14). Currently, only two mutations [c.1655T>A (p.Leu552*) and c.281G>A p.(Asp94Asn)] have been identified in association with this disease. Given the limited understanding of MODY14, it is imperative to identify additional cases and carry out comprehensive research on MODY14 and APPL1 mutations. To assess the pathogenicity of APPL1 gene mutations in diabetic patients and to characterize the functional role of the APPL1 domain. Patients exhibiting clinical signs and a medical history suggestive of MODY were screened for the study. Whole exome sequencing was performed on the patients as well as their family members. The pathogenicity of the identified APPL1 variants was predicted on the basis of bioinformatics analysis. In addition, the pathogenicity of the novel APPL1 variant was preliminarily evaluated through in vitro functional experiments. Finally, the impact of these variants on APPL1 protein expression and the insulin pathway were assessed, and the potential mechanism underlying the interaction between the APPL1 protein and the insulin receptor was further explored. A total of five novel mutations were identified, including four missense mutations (Asp632Tyr, Arg633His, Arg532Gln, and Ile642Met) and one intronic mutation (1153-16A>T). Pathogenicity prediction analysis revealed that the Arg532Gln was pathogenic across all predictions. The Asp632Tyr and Arg633His variants also had pathogenicity based on MutationTaster. In addition, multiple alignment of amino acid sequences showed that the Arg532Gln, Asp632Tyr, and Arg633His variants were conserved across different species. Moreover, in in vitro functional experiments, both the c.1894G>T (at Asp632Tyr) and c.1595G>A (at Arg532Gln) mutations were found to downregulate the expression of APPL1 on both protein and mRNA levels, indicating their pathogenic nature. Therefore, based on the patient's clinical and family history, combined with the results from bioinformatics analysis and functional experiment, the c.1894G>T (at Asp632Tyr) and c.1595G>A (at Arg532Gln) mutations were classified as pathogenic mutations. Importantly, all these mutations were located within the phosphotyrosine-binding domain of APPL1, which plays a critical role in the insulin sensitization effect. This study provided new insights into the pathogenicity of APPL1 gene mutations in diabetes and revealed a potential target for the diagnosis and treatment of the disease.

Bio-mechanical effects of femoral neck system versus cannulated screws on treating young patients with Pauwels type III femoral neck fractures: a finite element analysis

IntroductionAs a novel internal fixation for femoral neck fractures, the femoral neck system has some advantages for young Pauwels type III femoral neck fractures without clear biomechanical effects and mechanisms. Thus, the objection of the study is to realize the biomechanical effects and mechanism of FNS cannulated screws on treating young patients with Pauwels type III femoral neck fractures compared to cannulated screws which are commonly used for femoral neck fractures by finite element analysis.MethodsFirstly, the model of young Pauwels type III femoral neck fractures, femoral neck system (FNS), and three cannulated screws (CS) arranged in an inverted triangle were established, and the internal fixations were set up to fix young Pauwels type III femoral neck fractures. Under 2100 N load, the finite element was performed, and the deformation, peak von Mises stress (VMS), and contact at fracture segments were recorded to analyze the biomechanical effects and mechanism of FNS and three-CS fixing young Pauwels type III femoral neck fractures.ResultsCompared to three-CS, the deformation of the whole model, internal fixation, and fracture segments after FNS fixation were lower, and the peak VMS of the whole model and the internal fixation after FNS were higher with lower peak VMS of the distal femur and the fracture segments. With a sticking contact status, the contact pressure at fracture segments after FNS fixation was lower than that of three-CS.ConclusionsFNS can provide better mechanical effects for young patients with Pauwels type III femoral neck fractures, which may be the mechanical mechanism of the clinical effects of FNS on femoral neck fracture. Although there is high stress on FNS, it is still an effective and safe internal fixation for young patients with Pauwels type III femoral neck fractures.

EZH2 inhibitors promote β-like cell regeneration in young and adult type 1 diabetes donors

β-cells are a type of endocrine cell found in pancreatic islets that synthesize, store and release insulin. In type 1 diabetes (T1D), T-cells of the immune system selectively destroy the insulin-producing β-cells. Destruction of these cells leads to a lifelong dependence on exogenous insulin administration for survival. Consequently, there is an urgent need to identify novel therapies that stimulate β-cell growth and induce β-cell function. We and others have shown that pancreatic ductal progenitor cells are a promising source for regenerating β-cells for T1D owing to their inherent differentiation capacity. Default transcriptional suppression is refractory to exocrine reaction and tightly controls the regenerative potential by the EZH2 methyltransferase. In the present study, we show that transient stimulation of exocrine cells, derived from juvenile and adult T1D donors to the FDA-approved EZH2 inhibitors GSK126 and Tazemetostat (Taz) influence a phenotypic shift towards a β-like cell identity. The transition from repressed to permissive chromatin states are dependent on bivalent H3K27me3 and H3K4me3 chromatin modification. Targeting EZH2 is fundamental to β-cell regenerative potential. Reprogrammed pancreatic ductal cells exhibit insulin production and secretion in response to a physiological glucose challenge ex vivo. These pre-clinical studies underscore the potential of small molecule inhibitors as novel modulators of ductal progenitor differentiation and a promising new approach for the restoration of β-like cell function.

Soluble epoxide hydrolase gene deletion ameliorates retinal and ophthalmic arterial senescesome

Aims/Purpose: Neurovascular dysfunction in glaucoma is exacerbated by aging. We recently deciphered the crucial role of the cytochrome P450 (CYP) metabolic pathway in the retina (R) and ophthalmic artery (OA). Vasoactive CYP metabolites are hydrolysed by soluble epoxide hydrolase (sEH), thereby diminishing their protective effects. Hence, sEH has emerged as a novel inhibitory target. This study defined the neuro‐vasculoprotective molecular signatures of Ephx2 gene deletion (KO) that impinge senescence in the neural R and OA.Methods: Retinae and OA were isolated from young (3–5 months) and old (12–24 months) male wild type (WT) and KO mice. Samples were pooled (n = 5 mice/group/replicate) to yield 4 biological replicates per group and subjected to label‐free mass spectrometry‐based proteomics and in‐silico bioinformatics analyses.Results: A total of 3706 retinal and 644 OA proteins were identified. Aging profoundly affected the R and OA proteome of WT mice, as demonstrated by the differential expressions of 183 and 111 proteins, respectively. The key changes attributed to age‐related R cellular dysfunction and DNA damage were reflected in the inactivation of NAD+ (p = 9.1 × 10−4) and sirtuin (p = 6.2 × 10−3) signalling pathways. Remarkably, KO had a major influence on the regulation of R proteins involved in bioenergetics reprogramming via mitochondrial homeostasis in young mice, which was shown by the activation of oxidative phosphorylation (p = 1.3 × 10−6) and inhibition of mitochondrial dysfunction (p = 3.4 × 10−3), both of which corresponded to upstream involvement of UQCC3 (p = 7.3 × 10−7). A translation regulator, LARP1, which regulates cell proliferation and protein synthesis, was highly activated in the aged KO retina (p = 10 × 10−16) compared to aged WT (p = 3.1 × 10−5). In the OA, vascular remodelling processes observed in the aged WT mice, primarily compromised microtubule dynamics (3.6 × 10−8) and cell–cell contact (3.7 × 10−6), were significantly attenuated in the KO. Noteworthy, KO significantly mitigated proteome changes attributed to inflammatory response in the OA of both young and aged mice.Conclusions: In gist, the Ephx2 gene deletion significantly ameliorated detrimental senescesome in ocular neurovascular tissues. The potential use of sEH inhibitors for glaucoma needs further investigation.

Some new Young type inequalities

&lt;abstract&gt;&lt;p&gt;In this paper, we gave some generalized Young type inequalities due to Zuo and Li [J. Math. Inequal., 16 (2022), 1169-1178], and we also presented a new Young type inequality. As applications, we obtained some operator inequalities and matrix versions inequalities including the Hilbert-Schmidt norm and trace.&lt;/p&gt;&lt;/abstract&gt;

Some refinements of Young type inequalities

Some refinements of Young type inequalities

DNA methylation of promoter region inhibits galectin-1 expression in BMSCs of aged mice.

Senile osteoporosis increases fracture risks. Bone marrow stromal cells (BMSCs) are sensitive to aging. Deep insights into BMSCs aging are vital to elucidate the mechanisms underlying age-related bone loss. Recent advances showed that osteoporosis is associated with aberrant DNA methylation of many susceptible genes. Galectin-1 (Gal-1) has been proposed as a mediator of BMSCs functions. In our previous study, we showed that Gal-1 was downregulated in aged BMSCs and global deletion of Gal-1 in mice caused bone loss via impaired osteogenesis potential of BMSCs. Gal-1 promoter is featured by CpG islands. However, there are no reports concerning the DNA methylation status in Gal-1 promoter during osteoporosis. In the current study, we sought to investigate the role of DNA methylation in Gal-1 downregulation in aged BMSCs. The potential for anti-bone loss therapy based on modulating DNA methylation is explored. Our results showed that Dnmt3b-mediated Gal-1 promoter DNA hypermethylation plays an important role in Gal-1 downregulation in aged BMSCs, which inhibited β-catenin binding on Gal-1 promoter. Bone loss of aged mice was alleviated in response to in vivo deletion of Dnmt3b from BMSCs. Finally, when bone marrow of young wild-type (WT) mice or young Dnmt3bPrx1-Cre mice was transplanted into aged WT mice, Gal-1 level in serum and trabecular bone mass were elevated in recipient aged WT mice. Our study will benefit for deeper insights into the regulation mechanisms of Gal-1 expression in BMSCs during osteoporosis development, and for the discovery of new therapeutic targets for osteoporosis via modulating DNA methylation status.NEW & NOTEWORTHY There is Dnmt3b-mediated DNA methylation in Gal-1 promoter in aged bone marrow stromal cell (BMSC). DNA methylation causes Gal-1 downregulation and osteogenesis attenuation of aged BMSC. DNA methylation blocks β-catenin binding on Gal-1 promoter. Bone loss of aged mice is alleviated by in vivo deletion of Dnmt3b from BMSC.

Body mass index and characteristics of coronary plaque in younger patients with type 2 diabetes

Background and aimsThe association between the body mass index (BMI) and the characteristics of coronary plaque in younger type 2 diabetes (T2D) patients with coronary artery disease (CAD) remains to be elucidated. Methods and resultsA total of 138 consecutive younger (<65 years) T2D patients with CAD, who underwent optical coherence tomography imaging of the culprit lesion were included. The patients were classified into either the higher BMI group (n = 68) or the lower BMI group (n = 70) according to the median of BMI (25.9 kg/m2). The prevalence of thin-cap fibroatheroma (TCFA) (35.3 vs. 17.1 %, p = 0.015) was significantly higher in the higher BMI group than in the lower BMI group. The prevalence of TCFA was significantly higher in patients with higher BMI than in those with lower BMI among patients with hemoglobin A1c (HbA1c) ≥7.0 % (odds ratio [OR] 5.40, 95 % confidence interval [CI] 1.72–17.0, p = 0.003) although the significant difference was not observed among patients with HbA1c <7.0 % (OR 0.89, 95 % CI 0.25–3.13, p = 0.851). ConclusionHigher BMI was associated with a higher prevalence of TCFA in younger T2D patients with CAD, particularly in patients with HbA1c ≥ 7.0 %.

Clinical and genetic characteristics of maturity-onset diabetes of the young type 13: A systematic review of the literature.

Maturity-onset diabetes of the young type 13 (MODY13), a rare type of monogenic diabetes, is often misdiagnosed as type 1 or type 2 diabetes. To improve early diagnosis and precise treatment, we performed a systematic review and analysis of the literature about MODY13. PubMed, Cochrane, Embase, China National Knowledge Infrastructure (CNKI), Chinese BioMedical (CBM) Literature Database, and Wanfang Database were searched using the following search terms: "MODY13," "KCNJ11 maturity-onset diabetes of the young," "KCNJ11-MODY," "maturity-onset diabetes of the young type 13," and "neonatal diabetes mellitus KCNJ11." The demography, clinical characteristics, and gene mutations of patients were expressed with descriptive statistical methods. A total of 33 reports were included in this study, including 75 patients and 28 types of mutations. Thirty-six patients were male. The mean onset age was 25.20 ± 15.26 years. The averages of recorded body mass index, glycated hemoglobin (HbA1c), and fasting C-peptide were 23.45 ± 4.56kg/m2 , 10.07 ± 1.96%, and 0.31 ± 0.23nmol/L, respectively. Most of the mutation sites were located in the cytosolic region of N- and C-terminal domains of Kir6.2. Seven patients were reported to have diabetic chronic complications. MODY13 was diagnosed later than other types of MODY and was associated with low fasting C-peptide. Mutation sites of MODY13 were mostly concentrated in N- and C-terminal intracellular domains. The majority of KCNJ11 gene mutations causing MODY 13 were from G to A. The incidence rates of chronic complications were lower than type 1 and type 2 diabetes.

Study of the Soil Biome of a Young Intensive Type Apple Orchard

Study of the Soil Biome of a Young Intensive Type Apple Orchard

Maturity-onset diabetes of the young type 7 (MODY7) and mutation in the Krüppel-like transcription factor 11 (KLF11) gene.

Maturity-onset diabetes of the young type 7 (MODY7) and mutation in the Krüppel-like transcription factor 11 (KLF11) gene.

Complement factor H Y402H polymorphism results in diminishing CD4+ T cells and increasing C-reactive protein in plasma

Age-related macular degeneration (AMD) is a common cause of visual loss among the elderly. Genetic variants in the gene encoding complement factor H (CFH) have been identified as an AMD susceptibility gene, however, the mechanistic link is debated. Here, we investigated the link between the CFH Y402H genotype and low-grade inflammation. We recruited 153 healthy individuals, 84 participants with dry stages of AMD, and 148 participants with neovascular AMD. All participants were subjected to detailed retinal examination, and interview regarding comorbidities and lifestyle. Blood samples were analyzed for level of C-Reactive Protein (CRP), white blood cell differential count, and stained with fluorescent antibodies to differentiate CD4+ and CD8+ T cells. CFH Y402H genotyping was performed using an allele-specific polymerase chain reaction genotyping assay. Splenocytes from young and aged wild type and Cfh null mutant C57BL/6J mice were examined for CD4+ and CD8+ T cells. Healthy individuals with the CFH Y402H at-risk polymorphism HH had higher levels of CRP and lower proportions of CD4+ T cells compared to persons with the YH or YY polymorphism (P = 0.037, Chi-square). Healthy individuals with the HH polymorphism displayed lower proportions of CD4+ T cells with ageing (P < 0.01, one-way ANOVA), whereas both young and aged Cfh null mutant mice displayed lower proportions of CD4+ T cells (P < 0.001 and P < 0.05; unpaired t test). Participants with dry AMD and the HH polymorphism had similarly lower proportions of CD4+ T cells (P = 0.024, one-way ANOVA), but no difference in CRP-levels. In the neovascular stage of AMD, there was no difference in proportion of CD4+ cells or CRP levels according to genotype. The risk-associated CFH genotype is associated with an age-related decrease in proportion of CD4+ T cells and increased levels of CRP in healthy individuals. This indicates that decreased complement regulation results in extensive changes in innate and adaptive immune compartments that precede development of AMD.