Predicting cardiovascular risk in England and Wales: prospective derivation and validation of QRISK2

Objective To develop and validate version two of the QRISK cardiovascular disease risk algorithm (QRISK2) to provide accurate estimates of cardiovascular risk in patients from different ethnic groups in England and Wales and to compare its performance with the modified version of Framingham score recommended by the National Institute for Health and Clinical Excellence (NICE).Design Prospective open cohort study with routinely collected data from general practice, 1 January 1993 to 31 March 2008.Setting 531 practices in England and Wales contributing to the national QRESEARCH database.Participants 2.3 million patients aged 35-74 (over 16 million person years) with 140 000 cardiovascular events. Overall population (derivation and validation cohorts) comprised 2.22 million people who were white or whose ethnic group was not recorded, 22 013 south Asian, 11 595 black African, 10 402 black Caribbean, and 19 792 from Chinese or other Asian or other ethnic groups.Main outcome measures First (incident) diagnosis of cardiovascular disease (coronary heart disease, stroke, and transient ischaemic attack) recorded in general practice records or linked Office for National Statistics death certificates. Risk factors included self assigned ethnicity, age, sex, smoking status, systolic blood pressure, ratio of total serum cholesterol:high density lipoprotein cholesterol, body mass index, family history of coronary heart disease in first degree relative under 60 years, Townsend deprivation score, treated hypertension, type 2 diabetes, renal disease, atrial fibrillation, and rheumatoid arthritis.Results The validation statistics indicated that QRISK2 had improved discrimination and calibration compared with the modified Framingham score. The QRISK2 algorithm explained 43% of the variation in women and 38% in men compared with 39% and 35%, respectively, by the modified Framingham score. Of the 112 156 patients classified as high risk (that is, ≥20% risk over 10 years) by the modified Framingham score, 46 094 (41.1%) would be reclassified at low risk with QRISK2. The 10 year observed risk among these reclassified patients was 16.6% (95% confidence interval 16.1% to 17.0%)—that is, below the 20% treatment threshold. Of the 78 024 patients classified at high risk on QRISK2, 11 962 (15.3%) would be reclassified at low risk by the modified Framingham score. The 10 year observed risk among these patients was 23.3% (22.2% to 24.4%)—that is, above the 20% threshold. In the validation cohort, the annual incidence rate of cardiovascular events among those with a QRISK2 score of ≥20% was 30.6 per 1000 person years (29.8 to 31.5) for women and 32.5 per 1000 person years (31.9 to 33.1) for men. The corresponding figures for the modified Framingham equation were 25.7 per 1000 person years (25.0 to 26.3) for women and 26.4 (26.0 to 26.8) for men). At the 20% threshold, the population identified by QRISK2 was at higher risk of a CV event than the population identified by the Framingham score.Conclusions Incorporating ethnicity, deprivation, and other clinical conditions into the QRISK2 algorithm for risk of cardiovascular disease improves the accuracy of identification of those at high risk in a nationally representative population. At the 20% threshold, QRISK2 is likely to be a more efficient and equitable tool for treatment decisions for the primary prevention of cardiovascular disease. As the validation was performed in a similar population to the population from which the algorithm was derived, it potentially has a “home advantage.” Further validation in other populations is therefore advised.     

Determination of individual cell Michaelis-Menten constants.

BACKGROUND: A novel methodology for the measurement and analysis of apparent K(M) (Michaelis-Menten constant) and V(MAX) values of individual cells is suggested. It is based on a mathematical model that considers substrate influx into the cell, its intracellular enzymatic hydrolysis, and the product efflux. The mathematical formulation was approximated linearly in order to analyze intracellular substrate conversion characteristics via Michaelis-Menten theory. METHODS: Utilizing static cytometry, the time dependence of the fluorescence intensity [FI(t)] emitted from prelocalized and defined FDA stained cells was recorded. This required frequent periodical measurements of the same cells, which are sequentially exposed to various fluorogenic substrate concentrations. RESULTS: Model simulations correlated with experimental results. Differences in distributions of individual K(M) and V(MAX) values of cells incubated with and without PHA were evident. Average K(M) and V(MAX) values of PHA-stimulated cells increased by 99% and 540%, respectively. CONCLUSIONS: This study may provide a tool for assessing intracellular enzymatic activity in individual intact cells under defined physiologic conditions. This may open new vistas in various areas, giving answers to critical questions arising in the field of cell and developmental biology, immunology, oncology, and pharmacology.     

Foraging behaviour of Scymnus coccivora Ayyar against cotton mealybug Phenacoccus solenopsis Tinsley

Predation is one of the significant biotic mortality factors reducing the insect pest population as functional response and the numerical response of the predator are the key factor regulating the population dynamics of predator prey species. This study is aimed to evaluate the functional response of all the developmental stages of Scymnus coccivora Ayyar (Coleoptera: Coccinellidae) against the different densities of cotton mealybug, Phenacoccus solenopsis (Tinsley) (Hemiptera: Pseudococcidae) and the numerical response of female predator. Experiments were carried out in controlled environment laboratory conditions at 25 ± 1 °C temperature, 60 ± 5% relative humidity and photoperiod of 16 h. Number of eggs consumed, number of eggs laid and the Efficiency of Conversion of Ingested food (ECI) were recorded daily. Results from the study revealed that all the developmental stages of S. coccivora exhibited a Type II response. Different parameters such as attack rate (a’), handling time (T_h) and the maximum rate of predation were estimated using Roger’s random attack equation and Holling Disc equation in which Rogers random attack equation was found best fit. Female has shown the highest attack rate (a’) followed by IV^th instar grub, male, III^rd, II^nd and I^st instar grub. With low handling time, IV^th instar grub has shown maximum predation rate of 76.40 per day followed by female (75.86), male (58.79), III^rd (22.84), II^nd (19.65) and I^st instar grub (15.39). The numerical response increase was curvilinearly related to different prey densities with the highest number of eggs (11.8 ± 3.44) produced at highest prey density (160). The Efficiency of Conversion of Ingested food (ECI) was highest (64.49 ± 8.03) at prey density of 10. Understanding the factors that lead to variation in functional response of predator in natural population will advance our understanding of the effects of predation on individual and the effectiveness of coccinellid predators as biocontrol agent against cotton mealybug.     

Arabidopsis phospholipase D alpha 1-derived phosphatidic acid regulates microtubule organization and cell development under microtubule-interacting drugs treatment

Journal of Plant Research - Phospholipase D (PLD) and its product phosphatidic acid (PA) are emerging as essential regulators of cytoskeleton organization in plants. However, the underlying...     

Extracellular Matrix in Neural Plasticity and Regeneration

The extracellular matrix (ECM) is a fundamental component of biological tissues. The ECM in the central nervous system (CNS) is unique in both composition and function. Functions such as learning, memory, synaptogenesis, and plasticity are regulated by numerous ECM molecules. The neural ECM acts as a non-specific physical barrier that modulates neuronal plasticity and axon regeneration. There are two specialized types of ECM in the CNS, diffuse perisynaptic ECM and condensed ECM, which selectively surround the perikaryon and initial part of dendritic trees in subtypes of neurons, forming perineuronal nets. This review presents the current knowledge about the role of important neuronal ECM molecules in maintaining the basic functions of a neuron, including electrogenesis and the ability to form neural circuits. The review mainly focuses on the role of ECM components that participate in the control of key events such as cell survival, axonal growth, and synaptic remodeling. Particular attention is drawn to the numerous molecular partners of the main ECM components. These regulatory molecules are integrated into the cell membrane or disposed into the matrix itself in solid or soluble form. The interaction of the main matrix components with molecular partners seems essential in molecular mechanisms controlling neuronal functions. Special attention is paid to the chondroitin sulfate proteoglycan 4, type 1 transmembrane protein, neural-glial antigen 2 (NG2/CSPG4), whose cleaved extracellular domain is such a molecular partner that it not only acts directly on neural and vascular cells, but also exerts its influence indirectly by binding to resident ECM molecules.

     

Floral polymorphism in common primrose (Primula vulgaris Huds., Primulaceae) of the Northeastern Black Sea coast

The common primrose (Primula vulgaris, Primulaceae) has several color morphs. Two of them, traditionally treated as subspecies, vulgaris with white and yellow flowers, and polymorphic sibthorpii with the predominance of dark (anthocyanin-containing) flowers, often occur at the same places along the eastern Black Sea coast, stretching over 250?km between Novorossiysk and Pitsunda. Seventy-one primrose populations were sampled on almost every 10-km interval of this line. We found a significant trend of increase in the proportion of dark flowers in the populations from northwest to southeast, with an abrupt (60?km) transitional zone. Within this zone, we found significant spatial trends correlated with altitude and distance from seashore. No reliable morphological differences between color forms were found. The observed large-scale geographical structure may be a joint result of the recent contact of previously isolated color morphs, heterogeneity of pollinator preferences, and genetic drift.     

Ultrastructure of spermiogenesis and mature spermatozoon of Anonchotaenia globata (von Linstow, 1879) (Cestoda,Cyclophyllidea, Paruterinidae)

Yoneva, A., Georgieva, K., Mizinska, Y., Nikolov, P. N., Georgiev, B. B. and Stoitsova, S. R. 2010. Ultrastructure of spermiogenesis and mature spermatozoon of Anonchotaenia globata (von Linstow, 1879) (Cestoda, Cyclophyllidea, Paruterinidae). — Acta Zoologica (Stockholm) 91 : 184–192 The ultrastructure of spermiogenesis and of the spermatozoon of a species of the family Paruterinidae is described for the first time. The spermiogenesis of Anonchotaenia globata starts with the formation of a differentiation zone with two centrioles associated with thin striated roots. One of the centrioles gives rise to a free flagellum followed by a slight flagellar rotation and a proximodistal fusion of the flagellum with the cytoplasmic protrusion. This pattern corresponds to Type III spermiogenesis in cestodes. The spermatozoon consists of five distinct regions. The anterior extremity possesses an apical cone and a single helically coiled crested body. The cortical microtubules are spirally arranged. The axoneme is surrounded by a periaxonemal sheath and a thin layer of cytoplasm filled with electron‐dense granules in Regions I–V. The periaxonemal sheath is connected with the peripheral microtubules by transverse intracytoplasmic walls in Regions III and IV. The nucleus is spirally coiled around the axoneme. Anonchotaenia globata differs from Dilepididae (where paruterinids have previously been classified) in the type of spermiogenesis, the lack of glycogen inclusions and the presence of intracytoplasmic walls. The pattern of spermiogenesis is similar to that in Metadilepididae and Taeniidae, which are considered phylogenetically close to Paruterinidae.     

Proceedings from the Melanoma Research Foundation Mucosal Melanoma Meeting (December 16, 2022, New York,USA)

Mucosal melanoma remains a rare cancer with high mortality and a paucity of therapeutic options. This is due in significant part to its low incidence leading to limited patient access to expert care and downstream clinical/basic science data for research interrogation. Clinical challenges such as delayed and at times inaccurate diagnoses, and lack of consensus tumor staging have added to the suboptimal outcomes for these patients. Clinical trials, while promising, have been difficult to activate and accrue. While individual institutions and investigators have attempted to seek solutions to such problems, international, national, and local partnership may provide the keys to more efficient and innovative paths forward. Furthermore, a mucosal melanoma coalition would provide a potential network for patients and caregivers to seek expert opinion and advice. The Melanoma Research Foundation Mucosal Melanoma Meeting (December 16, 2022, New York, USA) highlighted the current clinical challenges faced by patients, providers, and scientists, identified current and future clinical trial investigations in this rare disease space, and aimed to increase national and international collaboration among the mucosal melanoma community in an effort to improve patient outcomes. The included proceedings highlight the clinical challenges of mucosal melanoma, global clinical trial experience, basic science advances in mucosal melanoma, and future directions, including the creation of shared rare tumor registries and enhanced collaborations.