There is, I think, something ethereal about i —the square root of minus one. I remember first hearing about it at school. It seemed an odd beast at that time—an intruder hovering on the edge of reality.

Usually familiarity dulls this sense of the bizarre, but in the case of i it was the reverse: over the years the sense of its surreal nature intensified. It seemed that it was impossible to write mathematics that described the real world in …

I and i

ポリープ状脈絡膜血管症におけるpachychoroid neovasculopathyの遺伝的・臨床的特徴

Epidemic Obesity and the Metabolic Syndrome

Diabetic retinopathy (DR), a sight-threatening neurovasculopathy, is the leading cause of irreversible blindness in the developed world. DR arises as the result of prolonged hyperglycemia and is characterized by leaky retinal vasculature, retinal ischemia, retinal inflammation, angiogenesis, and neovascularization. The number of DR patients is growing with an increase in the elderly population, and therapeutic approaches are limited, therefore, new therapies to prevent retinal injury and enhance repair are a critical unmet need. Besides vascular endothelial growth factor (VEGF)-induced vascular proliferation, several other mechanisms are important in the pathogenesis of diabetic retinopathy, including vascular inflammation. Thus, combining anti-VEGF therapy with other new therapies targeting these pathophysiological pathways of DR may further optimize treatment outcomes. Technological advancements have allowed for high-throughput proteomic studies examining biofluids such as aqueous humor, vitreous humor, tear, and serum. Many DR biomarkers have been identified, especially proteins involved in retinal inflammatory processes. This review attempts to summarize the proteomic biomarkers of DR-associated retinal inflammation identified over the last several years.

https://www.mdpi.com/1422-0067/20/19/4755/pdf

Proteomic Biomarkers of Retinal Inflammation in Diabetic Retinopathy.

Background
Postoperative vitreous cavity haemorrhage (POVCH) is a significant complication following vitrectomy for proliferative diabetic retinopathy (PDR). It delays visual recovery and can make further treatment difficult if the view of the fundus is significantly obscured. A number of interventions to reduce the incidence of POVCH have been proposed, including the perioperative use of anti-vascular endothelial growth factor (anti-VEGF). Anti-VEGFs reduce vascular proliferation and the vascularity of neovascular tissue, which is often the source of bleeding following vitrectomy.

Objectives
This updated review aimed to summarise the effects of anti-VEGF use to reduce the occurrence of POVCH after vitrectomy surgery for PDR.

Search methods
We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (2015, Issue 4), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to May 2015), PubMed (January 1966 to May 2015), EMBASE (January 1980 to May 2015), Latin American and Caribbean Health Sciences (LILACS) (January 1982 to May 2015), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov), and the the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 26 May 2015.

Selection criteria
We included all randomised controlled trials (RCTs) and quasi-RCTs that looked at the use of anti-VEGFs and the incidence of POVCH in people undergoing vitrectomy for PDR.

Data collection and analysis
Both review authors independently assessed and extracted the data. We used standard methodological procedures expected by Cochrane.

The primary outcomes of the review were the incidence of early and late POVCH following perioperative anti-VEGF administration. Secondary outcomes included best-corrected visual acuity at six months following surgery, the incidence of vitreous cavity washout or revision vitrectomy at six months, adverse effects of intervention (cataract, iris rubeosis and rubeotic glaucoma, retinal detachment, increased inflammation and systemic side effects), quality of life measures performed at least six months following vitrectomy, and density of POVCH.

Main results
The current review included 12 RCTs that looked at the pre- or intraoperative use of intravitreal bevacizumab to prevent postoperative vitreous haemorrhage during pars plana vitrectomy for complications of PDR. The studies were conducted in a variety of countries (three from Iran, two from Italy, two from Egypt, and the remaining from South Korea, USA, Mexico, Pakistan, and Japan). The inclusion criteria for entry into the studies were standard complications of proliferative retinopathy: non-clearing vitreous haemorrhage, tractional retinal detachment involving the macula, or combined tractional rhegmatogenous detachment. The included studies randomised a total of 654 eyes. The average age of the participants was 54 years.

We identified methodological issues in all included studies. Risk of bias was highest for masking of participants and investigators (four studies were an 'open label' design), and a number of studies were unclear when describing randomisation methods and sequence allocation.

Participants receiving intravitreal bevacizumab in addition to pars plana vitrectomy were less likely to experience early POVCH (grade 2) compared to people undergoing pars plana vitrectomy alone (risk ratio (RR) 0.28, 95% confidence interval (CI) 0.08 to 0.96, 2 studies, 144 eyes, high-quality evidence). This corresponds to an absolute effect of 130 fewer people (95% CI 167 fewer to 7 fewer) with early POVCH per 1000 people when treated with intravitreal bevacizumab. We saw similar results for all grades of POVCH (RR 0.35, 95% CI 0.23 to 0.53, 9 studies, 512 eyes) and when excluding cases where assessment of outcome was impossible due to presence of silicone oil (RR 0.34, 95% CI 0.19 to 0.60, 6 studies, 302 eyes).

The effect of pre- or intraoperative intravitreal bevacizumab on the incidence of late postoperative haemorrhage was uncertain (RR 0.72, 95% CI 0.30 to 1.72, 3 studies, 196 eyes, low-quality evidence). The absolute effect was 55 fewer people (95% CI 138 fewer to 143 more) with late POVCH per 1000 people when treated with intravitreal bevacizumab. This outcome was rarer and was only reported in a few studies. We are currently unable to provide an estimate of the effect of intravitreal bevacizumab on postoperative visual acuity due to significant study heterogeneity.

No local or systemic complications of intravitreal bevacizumab were reported by the RCTs. The risk of postoperative retinal detachment was lower in the participants treated with pre- or intraoperative bevacizumab (RR 0.46, 95% CI 0.19 to 1.08, 7 studies, 372 participants, low-quality evidence); the absolute effect was 49 fewer people (95% CI:73 fewer to 8 more) with postoperative retinal detachment per 1000 people when treated with intravitreal bevacizumab.

Authors' conclusions
The use of pre- or intraoperative bevacizumab lowers the incidence of early POVCH. The reported complications from its use appear to be low. Futher randomised studies that look at other anti-VEGF medications are ongoing and will strengthen the current review findings, giving both surgeons and patients evidence to guide treatment choices in the management of proliferative retinopathy.

/pdf/anti-vascular-endothelial-growth-factor-for-prevention-of-22o61y6jgs.pdf

Anti-vascular endothelial growth factor for prevention of postoperative vitreous cavity haemorrhage after vitrectomy for proliferative diabetic retinopathy.

Cardiovascular diseases are one of the most common causes of death in both developing and developed countries worldwide. Even though there have been improvements in primary prevention, the prevalence of cardiovascular diseases continues to increase in recent years. Hence, it is crucial to both investigate the molecular pathophysiology of cardiovascular diseases in-depth and find novel biomarkers regarding the early and proper prevention and diagnosis of these diseases. MicroRNAs, or miRNAs, are endogenous, conserved, single-stranded non-coding RNAs of 21-25 nucleotides in length. miRNAs have important roles in various cellular events such as embryogenesis, proliferation, vasculogenesis, apoptosis, cell growth, differentiation, and tumorigenesis. They also have potential roles in the cardiovascular system, including angiogenesis, cardiac cell contractility, control of lipid metabolism, plaque formation, the arrangement of cardiac rhythm, and cardiac cell growth. Circulating miRNAs are promising novel biomarkers for purposes of the diagnosis and prognosis of cardiovascular diseases. Cell or tissue specificity, stability in serum or plasma, resistance to degradative factors such as freeze-thaw cycles or enzymes in the blood, and fast-release kinetics, provide the potential for miRNAs to be surrogate markers for the early and accurate diagnosis of disease and for predicting middle- or long-term prognosis. Moreover, it may be a logical approach to combine miRNAs with traditional biomarkers to improve risk stratification and long-term prognosis. In addition to their efficacy in both diagnosis and prognosis, miRNA-based therapeutics may be beneficial for treating cardiovascular diseases using novel platforms and computational tools and in combination with traditional methods of analysis. microRNAs are promising, novel therapeutic agents, which can affect multiple genes using different signaling pathways. miRNAs therapeutic modulation techniques have been used in the settings of atherosclerosis, acute myocardial infarction, restenosis, vascular remodeling, arrhythmias, hypertrophy and fibrosis, angiogenesis and cardiogenesis, aortic aneurysm, pulmonary hypertension, and ischemic injury. This review presents detailed information about miRNAs regarding structure and biogenesis, stages of synthesis and functions, expression profiles in serum/plasma of living organisms, diagnostic and prognostic potential as novel biomarkers, and therapeutic applications in various diseases.

/pdf/microrna-and-cardiovascular-diseases-3lamu2mlx1.pdf

MicroRNA and Cardiovascular Diseases

Mitral valve prolapse (MVP) has been long known for causing susceptibility for ventricular arrhythmogen- esis, and this risk was evaluated by various methods, mostly by using QT interval related measurements on surface electrocardiogram. T wave peak to end (Tp-e) interval is a relatively new marker for ventricular arrhythmogenesis and repolarization heterogeneity. Prolongation of this interval represents a period of potential vulnerability to re-en- trant ventricular arrhythmias. However, there is no information available assessing the Tp-e interval and related cal- culations in patients with MVP. The aim of this study was to assess ventricular repolarization in patients with MVP by using QT, corrected QT (QTc) and Tp-e interval, Tp-e/QT ratio, and Tp-e/QTc ratio. Electrocardiogram of consecutive 72 patients, who were followed by outpatient clinic because of mitral valve prolapse, were obtained and scanned. Electrocardiograms of age and sex matched 60 healthy control individuals were also gained for comparison. QT, QTc, Tp-e/QT and Tp-e/QTc were calculated. Baseline characteristics were similar in both groups. QT (405.1±64.3 vs. 362.1±39.1; p<0.001), QTc (457.6±44.4 vs. 428.3±44.7; p<0.001), Tp-e (100.2±22.1 vs. 74.6±10.2; p<0.001) and Tp-e/QT (0.24 vs. 0.20; p<0.001) and Tp-e/QTc (0.21 vs. 0.17; p<0.001) were significantly worse in MVP group. Our study revealed that Tp-e interval and Tp-e/QT ratio were increased in MVP patients. Tp-e interval and Tp-e/QT ratio might be a useful marker of cardiovascular morbidity and mortality due to ventricular arrhythmias in patients with MVP.

https://www.ijcem.com/files/ijcem0000739.pdf

Original Article Assessment of ventricular repolarization inhomogeneity in patients with mitral valve prolapse: value of T wave peak to end interval

The purpose of this study was to evaluate the effect of blood pressure (BP) rhythm on the values of Tp-Te interval and Tp-Te/QT ratio in patients with metabolic syndrome. Seventy patients with newly diagnosed hypertension who fulfilled the metabolic syndrome criteria according to the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (NCEP/ATP-III) were evaluated with 24-hour blood pressure holter monitoring. According to blood pressure rhythm, 35 patients with dipper blood pressure pattern and 35 patients with non-dipper blood pressure pattern were enrolled as two groups in our study. QT, corrected QT (QTc), Tp-Te interval and Tp-Te/QT ratio were measured from the 12-lead electrocardiogram. These parameters were compared between the groups. The nocturnal systolic and diastolic blood pressures were significantly higher in non-dipper patients than the dipper group. Baseline characteristics and QT, QTc intervals were similar in both groups. Tp-Te (91±12.24 vs 74±9.96; p < 0.001), Tp-Te/QT (0.24±0.027 vs 0.20±0.025; p < 0.001) and Tp-Te/QTc (0.22±0.023 vs 0.18±0.023; p < 0.001) were significantly increased in non-dipper group. These findings suggest that Tp-Te interval, Tp-Te/QT ratio end Tp-Te/QTc ratio were prominently increased in non-dipper hypertensive patients than dippers with metabolic syndrome.

Effect of non-dipper and dipper blood pressure patterns on Tp-Te interval and Tp-Te/QT ratio in patients with metabolic syndrome.

We evaluated the effect of intravitreal bevacizumab (IVB) injection before pars plana vitrectomy (PPV) on intravitreal hemorrhage (VH) during and after vitrectomy for postoperative the first day and the first month in pseudophakic patients with proliferative diabetic retinopathy (PDR). This retrospective study was performed on 44 eyes of 44 patients who underwent vitrectomy for PDR. Patients were divided into PPV (n = 22 eyes) and PPV + IVB (n = 22 eyes) groups. Injection of bevacizumab (1.25 mg/0.05 mL) was performed 3 days before vitrectomy. Outcomes of visual acuity as well as intraoperative and postoperative VH were compared between the two groups. One month after surgery, visual acuity improved in PPV and PPV + IVB groups (P = 0.005, P = 0.006), respectively. There was no difference between the two groups in best corrected visual acuity at baseline and after vitrectomy (P = 0.71). Intraoperative bleeding into the vitreous was recorded in 14 (63.6%) cases in the PPV group and in 7 (31.8%) cases in the PPV + IVB group. The first month, intravitreal hemorrhage was recorded in six patients in the PPV group and in two patients in the PPV + IVB group (P = 0.03). The mean pre-postoperative central macular thickness was similar in both groups. Intravitreal injection of IVB before vitrectomy decreased the rate of VH at the time of surgery and at the first postoperative month in patients with PDR.

Effect of Bevacizumab Injection before Vitrectomy on Intravitreal Hemorrhage in Pseudophakic Patients with Proliferative Diabetic Retinopathy.

An increase in macular thickness due to fluid accumulation in the macula in patients with diabetes mellitus. Optical coherence tomography (OCT) has been shown to be highly reproducible in measuring macular thickness in normal individuals and diabetic patients. OCT can detect subtle changes of macular thickness. The aim of this study is to compare central macular thickness (CMT) of diabetic patients with type 2 diabetes without clinical retinopathy and normal controls, in order to assess possible increased macular thickness associated with diabetes mellitus.

/pdf/cental-macular-thickness-in-patients-with-type-2-diabetes-522js9ztlz.pdf

Mehmet Demir

Papers

MicroRNA and Cardiovascular Diseases

Original Article Assessment of ventricular repolarization inhomogeneity in patients with mitral valve prolapse: value of T wave peak to end interval

Effect of non-dipper and dipper blood pressure patterns on Tp-Te interval and Tp-Te/QT ratio in patients with metabolic syndrome.

Effect of Bevacizumab Injection before Vitrectomy on Intravitreal Hemorrhage in Pseudophakic Patients with Proliferative Diabetic Retinopathy.

Cental macular thickness in patients with type 2 diabetes mellitus without clinical retinopathy