bluuebunny/crossref_metadata_2025 huggingface dataset:
Correlation between obesity and serum 25-hydroxyvitamin D levels in patients with type 2 diabetes
Authors: HE Yuli
Published: April 2024

[Objective] The paper analyzes the correlation of vitamin D level with obesity degree and serum 25-hydroxyvitamin D level in patients with type 2 diabetes mellitus (T2DM) through clinical case studies, which can provide clinical guidance for obese T2DM patients' weight control to lower their risk of developing metabolic illnesses. [Methods] A total of 249 patients with T2DM were chosen from among those hospitalized at Lanzhou University's First Hospital between April and September of 2023. The serum 25-hydroxyvitamin D level, body fat rate, fasting blood glucose, and fasting insulin of the subjects were detected, and 198 T2DM patients with low serum 25-hydroxyvitamin D levels were selected as the observation group. 51 T2DM patients with normal serum 25-hydroxyvitamin D levels were selected as the control group, and the correlation between type 2 diabetes mellitus and vitamin D levels and obesity was analyzed. [Results] Obesity and serum vitamin D insufficiency are associated with type 2 diabetes. Both vitamin D deficiency and obesity eventually lead to T2D, endocrine disorders, and other common diseases. [Conclusions] Low plasma 25-hydroxyvitamin D (25[OH]D) concentration and high BMI are correlated with an increased risk of diabetes.
Complications of tattoo removal
Authors:   Dr Derm Bőrgyógyászati Anti-Aging Központ, Esztétikai Lézer és Plasztikai Sebészet, Budapest, Varju Gábor
Published: April 2024

Non-laser and laser methods of tattoo removal are described in the publication. The complications of incorrect intervention in tattoo artist studios and beauty salons are illustrated with clinical photos. The complication of laser and chemical treatment performed by a layman, causing a significant aesthetic problem in two cases is presented. The challenges that arise during the restoration are demonstrated. The publication draws attention to the difference in power density between Q-switched lasers and other types of lasers, and to the risks of tattoo removal procedures, such as permanent scars, allergic reactions or perforation of the retina (FTMH), with complete loss of vision in case of unqualified personnel.
Treatment of the tear trough deformity with hyaluronic acid – the optimal result
Authors:   Dermart Bőrgyógyászati Magánrendelés Budapest, Pónyai Katinka , Baranyai Fanni , Czirbesz Kata , Haller Ákos
Published: April 2024

Volume replacement of the tear trough deformity by hyaluronic acid is one of the most popular procedures in aesthetic patients. However, the inadequate indication, choice of material or technique, the irrational expectations and over-treatment may lead to unwanted complications and dissatisfaction of the patients. Moreover, they induce protracted corrective procedures. The object of our article is to make the aesthetic doctor’s job easier by providing important knowledge of do’s and don’ts before, during and after this type of procedure
Curta-metragem na sala de aula: multiletramento e sequência didática
Authors: Vasconcelos Francisco Fábio Pinheiro de , Silva Eliene Ramos da
Published: April 2024

Este livro tem como foco o aprimoramento da competência leitora dos estudantes através da linguagem verbo-audiovisual por meio das narrativas fílmicas do gênero curta-metragem.
The Australian blood lime described and named: Citrus × sykesii Mabb. (Rutaceae-Aurantioideae-Aurantieae)
Authors: Mabberley David John
Published: April 2024

The Australian blood lime of commerce is formally described and named Citrus × sykesii Mabb., hybrida nova.
First Report of Alaria spp. in Domestic Feline in Southern Brazil
Authors: Ferraz Alexsander , Ongaratto Renata Fontes , Capella Gabriela de Almeida , Santos Rodrigo Leite dos , Braga Ana Carolina Aquino , Reichow Ana Clara Dornelles , Santos Victória da Porciúncula dos , Bierhals Eduarda Santos , Moreira Tiago Felipe Barbosa , Nizoli Leandro Quintana
Published: April 2024

Alaria spp. are trematodes that have a heteroxenous life cycle, requiring two intermediate hosts and several paratenic and definitive hosts. Alaria alata is considered a potential cause of disease in humans and is included among several emerging zoonotic parasites. It is the etiological agent of alariosis, which is associated with the consumption of raw or undercooked meat from intermediate (snails, frogs) or paratenic (mainly game) hosts of the parasite. This work aimed to report the first case of alariosis in a domestic feline in southern Brazil. The patient in this report was an adult male feline of no defined breed, who a few days after being adopted, began to present loose stools, which progressed to diarrhea, and some episodes of vomiting were also reported. The definitive diagnosis was obtained from coproparasitological examination, using the Hoffman, Pons, and Janer technique (spontaneous sedimentation), where Alaria spp. eggs were observed. Following the diagnosis, treatment with praziquantel (20mg/kg) was instituted for two consecutive days, as well as supportive therapy. At the end of the treatment, a new coproparasitological examination was carried out, which confirmed the effectiveness of the treatment. This report suggests, the importance of researching and reporting cases involving the trematode Alaria spp. becomes evident, as it represents not only a health problem for domestic animals but also a public health problem due to its zoonotic potential.
Plant-Based Insecticides for Control of Aedes aegypti, Sitophilus zeamais and Nasutitermes corniger: A Review and Bibliometric Analysis
Authors: Santos Lucas Gabriel Pita dos , Costa Beatriz de Aquino Marques da , Almeida Welton Aaron de , Silva Talyta Naldeska da , Coutinho Gabriel da Silva , Napoleão Thiago Henrique , Porto Tatiana Souza , Pontual Emmanuel Viana
Published: April 2024

Insect pests can transmit diseases or affect the economy and their uncontrolled growth is intensified by human activity, which has affected ecosystems and interfered with trophic chains. Aedes aegypti L. transmits dengue, chikungunya, zika and yellow fever, while Sitophilus zeamais Motsch is a stored grain pest, and Nasutitermes corniger Motsch attacks trees and urban buildings. This work provides a review of the state of art and current trends, as well as a bibliometric analysis on the insecticidal activity of plant-based products against Ae. aegypti, S. zeamais and N. corniger. The review of literature data showed that plant insecticides comprise secondary metabolites and proteins that can impair the viability of embryos, larvae, pupae, and adults, as well as fertility and oviposition or feeding behavior of insects. Also, they tend to be more biodegradable and less harmful to non-target organisms compared to synthetic insecticides. The bibliometric analysis revealed the concentration of publications in tropical regions worldwide, where there is a strong occurrence of diseases transmitted by Ae. aegypti. These reports were far more numerous than those on N. corniger and S. zeamais. Furthermore, the synthesis of metallic nanoparticles from plant products has strongly emerged as a current trend.
The Impact of Rainfall on Oil Palm Production: A Case Study in Berau Regency, East Borneo, Indonesia
Authors: Anwar Rusli , Rahman Arief
Published: April 2024

This study examines the impact of rainfall on oil palm growth and productivity in the Berau region of East Borneo, Indonesia. The research utilized qualitative and quantitative field studies, employing correlation and regression analysis. The study focused on the oil palm plantation area as its subject. Data was collected from a plantation in the Berau region of East Borneo. The plantation has homogeneous plant age (same planting year, 2009) and homogeneous progeny (Scofindo variety) and is included in the company's core plantation. The observation parameters included rainfall, rainy days, fresh fruit bunches, and plant productivity. It was found that rainfall and rainy days have an impact on oil palm productivity. The regression results indicate a positive correlation between rainfall and oil palm productivity, with a correlation coefficient of 0.025109171. However, rainy days have a negative effect on oil palm productivity, with a correlation coefficient of -0.036778304, despite being positively correlated with rainfall. The correlation coefficient of 0.768386269 indicates a direct impact on reducing oil palm productivity. Rainfall indirectly affects oil palm productivity by influencing temperature, humidity, intensity, and length of daily irradiation. These factors directly affect the productivity of oil palm plants.
Barium Titanate Nanoparticles Exhibit Cytocompatibility in Cultured Bovine Fibroblasts: A Model for Dermal Exposure
Authors: Onorato Geovana de Carvalho , Amaral Danielle Luciana Aurora Soares do , Oliveira Luiz Fernando Cappa de , Brandao Humberto de Mello , Munk Michele
Published: April 2024

The emergence of barium titanate nanoparticles (BaTiO3 NPs) represents an advancement in various fields such as technology, health, and agribusiness. However, increased production heightens the risk of their dispersion into the environment, thereby raising concerns about potential exposure to animals and humans, including the risk of dermal exposure. This study explores the chemical-physical properties of BaTiO3 NPs and their cytocompatibility using a bovine fibroblast cell model. The size and Zeta potential of the NPs were analyzed using scanning electron microscopy and dynamic light scattering technique. Raman spectroscopy was used to characterize the composition of the BaTiO3 NPs. Bovine fibroblasts were exposed in vitro to NPs (0.1 to 100 µg mL-1) for 24 hours to evaluate the cytocompatibility using the Thiazolyl Blue Tetrazolium Bromide assay and Trypan Blue exclusion test. The data were evaluated by analysis of variance and the means compared by the Tukey test. Scanning electron microscopy revealed that BaTiO3 NPs measured approximately 100 nm. Dynamic light scattering analysis indicated a hydrodynamic size of 149.27 nm with a polydispersion index of 0.37, and the Zeta potential was -13mV. Raman spectroscopy analysis highlighted the cubic phase of BaTiO3 NPs. Cytotoxicity tests demonstrated that BaTiO3 NPs did not affect cell viability, with 10 µg mL-1 resulting in enhanced cell proliferation. Overall, these findings underscore the non-toxic characteristics of BaTiO3 NPs in fibroblast cells, positioning them as promising and cytocompatible nanomaterials.
Knowledge Gap and Safe Use of Pesticides by Vegetable Growers of Bihar, India
Authors: Kumari Rashmi , Panda Chandan Kumar , Paswan Anil
Published: April 2024

In this study, knowledge about pesticides and their safe use among vegetable growers of Purnea district was discussed. Data were collected from vegetable growers of Purnea district of Bihar. From the district, one block was purposively chosen. Three villages from one block, comprising of 50 respondents each were randomly chosen. The sample size was 150 vegetable growers. Frequency, percent, weighted mean and rank were used to analyze the data. It was found that majority of the respondents lack knowledge about banned pesticides and label on pesticide products. Finding discloses that there was lack of knowledge about proper disposal of pesticide and lack of knowledge about using protective clothing. Farmers’ age, educational level, experience has positive effects on safe use of pesticides in vegetable cultivation. Under such condition, there is need of extension agents in establishing rapport with farmers on regular basis can help in enhancing knowledge level about safe use of pesticides among vegetable growers.
Effect of Soil and Foliar Application of Humic Acid on Nutrient Uptake, Grain and Straw Yield of Black Gram (Vigna mungo L.) under Inceptisols
Authors: Vinod Shendare Dinesh , Ramrao Hanwate Gautam , Madhukar Khade Pradip , Vyankatrao Kale Swati , Prakashrao Thakare Shreyash
Published: April 2024

Black gram is a type of legume that is widely cultivated and consumed in various parts of the world. It is believed to have originated in the Indian subcontinent and is one of the oldest cultivated legumes in the world. The field experiment was carried out to during kharif season of the year 2022 at departmental farm of Soil Science and Agricultural Chemistry, College of Agriculture, Latur. The experiment was laid out in randomized block design with three replications and eight treatments viz., T1 (RDF), T2 (RDF + Foliar application of humic acid @ 0.2 % at 20 & 35 DAS), T3 (RDF + soil application of humic acid @ 10 kg ha-1), T4 (RDF + soil application of humic acid @ 15 kg ha-1), T5 (RDF + soil application of humic acid @ 20 kg ha-1), T6 (T3 + foliar application of humic acid @ 0.2% at 20 & 35 DAS), T7 (T4 + foliar application of humic acid @ 0.2% at 20 & 35 DAS), T8 (T5 + foliar application of humic acid @ 0.2% at 20 & 35 DAS). The field study indicated that the nutrient uptake and content  and grain and straw yield of black gram crop were significantly influenced due to soil and foliar application of humic acid and RDF. The uptake of N, P and K  were recorded at harvest. Significant and maximum uptake of  N, P and K were noticed with application of treatment T8 (RDF + soil application of humic acid @ 20 kg ha-1+ foliar application of humic acid @ 0.2% at 20 and 35 DAS), whereas the T1 (RDF) showed least values. grain and straw yield significantly affected due to T8 (RDF + soil application of humic acid @ 20 kg ha-1 + foliar application of humic acid @ 0.2% at 20 and 35 DAS) and the lowest grain and straw yield were recorded in T1 (RDF). Thus, it can be concluded that the soil and foliar application of humic acid increase the nutrient uptake and grain and straw yield. The significantly superior result recorded by treatment T8 (RDF + soil application of humic acid @ 20 kg ha-1 + foliar application of humic acid @ 0.2% at 20 and 35 DAS) next to this treatment T7 (RDF + soil application of humic acid @ 10 kg ha-1 + foliar application of humic acid @ 0.2% at 20 and 35 DAS) was best option. The significant increase in grain and straw yield of black gram was due to application of RDF with soil and foliar application of humic acid which mitigates scarcity, increased absorption effectively and increased photosynthetic activity which leads to higher grain and straw yield.
Uniform Estimates on Length of Programs and Computing Algorithmic Complexities for Quantitative Information Measures
Authors: Verma Rohit Kumar , Laxmi M. Bhagya
Published: April 2024

Shannon entropy and Kolmogorov complexity are two conceptually distinct information metrics since the latter is based on probability distributions while the former is based on program size. All recursive probability distributions, however, are known to have an expected Up to a constant that solely depends on the distribution, the Kolmogorov complexity value is equal to its Shannon entropy. We investigate if a comparable correlation exists between Renyi and Havrda- Charvat Entropy entropies order α, indicating that it is consistent solely with Renyi and Havrda- Charvat entropies of order 1.
Kolmogorov noted that the characteristics of Shannon entropy and algorithmic complexity are comparable. We examine a single facet of this resemblance. Specifically, linear inequalities that hold true for Shannon entropy and for Kolmogorov complexity. As it happens, the following are true: (1) all linear inequalities that hold true for Shannon entropy and vice versa for Kolmogorov complexity; (2) all linear inequalities that hold true for ranks of finite subsets of linear spaces for Shannon entropy; and (3) the reverse is untrue.
Influence of Phosphorus and Sulphur Levels on Economics and Yield of Safflower (Carthamus tinctorius L.) under the Eastern Zone of UP, India
Authors: Singh Ravin , Sanodiya Lalit Kumar , Kumar Ravendra , Singh Shaurya
Published: April 2024

The present study highlights the influence of Phosphorus and Sulphur Levels on Economics and Yield of Safflower (Carthamus tinctorius L.): A Field Experiment yield of Safflower (Carthamus tinctorius L)". var. "ISF-764" was tested at Crop Research Farm during Rabi 2021–23. Ministry of Agriculture Sciences and technology United University, Prayagraj in the U.P. Safflower (Carthamus tinctorius L.) India ranks second in terms of planted area after food crops and is the world's fourth-largest producer of oilseeds in terms of output. The soil of the experimental plot had a sandy loam texture, was almost pH-neutral (7.5), had low organic carbon content (0.50%), and was readily available. N (228.59 kg/ha), available P (29.80 kg/ha) and available K (125.21 kg/ha). The experiment was laid out in randomized block design with nine treatments consists three level of S 20,30,40 kg/ha and three level of P 30,40,50 kg/ha with control (Farmer practice) were replicated thrice. Results obtained that higher plant height (173.33 cm), Number of branches (19.27), dry weight (117.89 g/day), yield attributes and yield viz., seed yield (2.20 t/ha), stover yield (2.98 t/ha) and Hi (42.44 %) were recorded with the application of 40 kg/ha S + 50 kg/ha P, economics viz. however, higher gross return (113804.07 INR/ha), net return (77799.97 INR/ha) and B:C ratio (2.16) was observed when 40 kg/ha S and 50 kg/ha P were applied. Application of 40 kg/ha S with 50 kg/ha P was therefore more productive and financially viable. It is concluded that treatment T9 with application of S 40 kg/ha + P 50 kg/ha was found to be the best that recorded highest plant height, number of capitulam / plant , dry weight (g), panicle length, number of panicles, number of grains per panicle, seed yield, straw yield, test weight and harvest index.
Application of Airborne Magnetic Data to Assess the Structures that Favour Gold Mineralization within Southern Parts of Katsina State, Nigeria
Authors: A. F. Akpaneno, , M. D Tawey,
Published: April 2024

The Nigerian schist belts are endowed with gold mineralisation and to delineate the geological structures that favour gold mineralisation, the airborne magnetic data that cover the study area was employed. Also, the residual magnetic anomaly data of the research area was reduced to the Equator (RTE) followed by the application of the centre for exploration targeting (CET) plug-in and three source edge mapping techniques; analytic signal (AS), first vertical derivative (FVD) and the horizontal gradient magnitude (HGM), for structural delineation and subsequently the structural density map of the area was produced. Structural density varies from 0.186 km/km2 low to 0.93 km/km2 high. Portions within the study area with high structural densities are Bakori in the southwest, Shanono in the northeast, Gwarzo situated directly south of Shanono, north and south of Karaye, the border between Kafur and Rogo in the south, all within the schist. Since structures are conduits for the migration of mineralisation fluids, areas with high structural densities will be viable for gold mineralisation. Also, comparing the structural density map of the area to the analytic signal map of the area has revealed the high structural density portions to coincide with the high analytic signal zones. This implies that structures within these portions are responsible for the migration of mineralization fluid into these environments.
Principles and Applications of Agroecology: A Review
Authors: Dushyant . , Sharma Krashanakant , Roy Shalini , Rooma Km. , Mahan Nisha , Kumar Praveen , Kumar Manish , Singh Sudhir Kumar , Kumar Brijesh , Hussain Arshad , Sujal .
Published: April 2024

Agroecology is a holistic approach to agriculture that combines ecological principles with farming systems. Its primary goal is to create sustainable, resilient, and productive agricultural ecosystems. In this review, we will explore the fundamental ideas and various applications of agroecology. We will delve into the biological components of agricultural landscapes, focusing on natural pest control, biodiversity, and nutrient cycling. Furthermore, we will showcase successful case studies from different regions, demonstrating how agroecology benefits smallholder farmers, food security, and climate resilience. However, we will also address obstacles to its widespread adoption, such as technological and regulatory challenges. Additionally, we will examine the environmental impacts of agroecology compared to traditional agriculture, emphasizing how it promotes soil health, conserves biodiversity, and mitigates climate change. Taking into account its social and economic aspects, we will underscore the importance of preserving indigenous knowledge while highlighting the economic feasibility of agroecology and its empowering effects on local communities. The review will conclude by emphasizing the need for scalable techniques, improved research, and supportive policies to fully integrate agroecology into mainstream agricultural practices, thereby creating a resilient and sustainable agricultural environment. We will also propose potential pathways towards achieving this goal.
Unveiling Urban Canines: Leveraging Single-sight and Sight–resight Survey for Street Dog Population Estimation and Enhanced Rabies Surveillance in Metropolitan City of Bruhat Bengaluru Mahanagara Palike, Karnataka, India
Authors: R. Raaga , K. P. Suresh , Hemadri Divakar , Gulati Baldev Raj , T. Chandraiah , Chandrashekar Balaji , K. P. Ravi Kumar , S. M. Manjunath Shinde. , Isloor Shrikrishna , G. K. Asha , K. L. Rudresh Kumar , R. Balaji
Published: April 2024

Aim: The aim of the study is to estimate Bengaluru's street dog population and evaluate the effectiveness of interventions for population control and public health, particularly in rabies control. It also aims to develop a blueprint for responsible urban management that prioritizes compassion and safety for both humans and street dogs.
Study Design and Methodology: The study utilizes the Bruhat Bengaluru Mahanagara Palike (BBMP) Street Dog Survey to estimate the street dog population in Bengaluru. It employs Single-Sight and Sight–Resight methods with Lincoln–Petersen's Formula and Chapman’s Correction for estimation. The population is categorized into zones to provide nuanced insights, guiding targeted interventions based on gender, age composition, and neutering status. During the initial six days, a single-sight survey was conducted by a pair of surveyors traveling on a 2-wheeler down every road in an allocated zone, photographing and recording details of dogs observed. Subsequently, on the following six days, all dogs sighted during the initial survey period were documented, regardless of whether they were previously recorded.
Results: The study estimates Bengaluru's street dog population at approximately 279335. It indicates a significant 10% reduction in the street dog population since 2019 which had estimated it at 309898, suggesting effective interventions. There is also a commendable 20% increase in neutering rates from an estimated 51.16% in 2019 to 71.85% in the present study, highlighting the importance of ongoing efforts in population control and public health, particularly in rabies control.
Conclusion: The reduction in the street dog population is deemed pivotal for curtailing disease transmission and ensuring public safety. The study positions itself to develop a blueprint for responsible urban management, prioritizing compassion and safety for both humans and street dogs. By exemplifying the effectiveness of evidence-driven policies and collective action, the aim is to pave the way for sustainable urban management practices that foster harmonious coexistence between communities and street dogs. Through continued collaboration and informed decision-making, the study suggests striving towards creating a safer and more compassionate environment for all inhabitants of Bengaluru.
Highly Diastereo‐ and Enantioselective Direct Aldol Reactions Promoted by Water‐Compatible Organocatalysts Bearing Central and Axial Chiral Elements
Authors: Peng Fang‐Zhi , Shao Zhi‐Hui , Pu Xue‐Wei , Zhang Hong‐Bin
Published: August 2008

Two novel bifunctional primary amine catalysts 1 (RA,S,S) and 2 (RA,R,R), which bear both central and axial chiral elements, have been developed to promote highly diastereoselective and enantioselective aldol reactions of arylaldehydes with cyclic and acyclic ketones in the presence of water at room temperature. The catalyst 2 (RA,R,R) afforded the desired products with high levels of anti diastereoselectivity (up to 99:1) and enantioselectivity (up to 98%), showing that the two chiral elements of catalyst 2 (RA,R,R) are matched, and enhance the stereochemical control. In addition, the catalyst 2 (RA,R,R) was found to catalyze the direct aldol reaction of 4‐nitrobenzaldehyde with 2‐cyclohexanone under neat reaction conditions at room temperature with the high anti diastereoselectivity (98:2) and enantioselectivity (98%).
Positive association between SAT‐1 −1415T/C polymorphism and anxiety
Authors: Vaquero‐Lorenzo Concepción , Riaza Bermudo‐Soriano Carlos , Perez‐Rodriguez M. Mercedes , Diaz‐Hernandez Montserrat , López‐Castromán Jorge , Fernandez‐Piqueras Jose , Saiz‐Ruiz Jeronimo , Baca‐Garcia Enrique
Published: August 2008

Limbic glutamatergic neurotransmission plays a pivotal role in the pathogenesis of anxiety disorders. Polyamines modulate the activity of several ionotropic glutamate receptors and have been involved in the regulation of fear‐conditioning response. Spermidine/spermine N1‐acetyltransferase (SSAT‐1) is the main enzyme regulating polyamine catabolism. The aim of the present study was to examine the association between anxiety disorders and the −1415T/C (rs1960264) single nucleotide polymorphism (SNP) of the gene (SAT1) coding for SSAT‐1. A case–control design was used in order to compare the genotypes for the −1415T/C (rs1960264) SNP between anxiety patients (n = 218), other non‐anxiety psychiatric patients (n = 362), and healthy controls (n = 251). DSM‐IV diagnoses were provided using MINI 4.4. Genomic DNA was extracted from peripheral blood samples collected from participants. In males, there was a significant difference in the distribution of the two genotypes (T and C) for the SAT‐1 −1415T/C SNP between anxiety patients, non‐anxiety psychiatric controls, and healthy controls. The T genotype was significantly more frequent in males suffering from anxiety disorders than in male psychiatric controls and healthy controls. This is the first study linking polymorphic variants of genes involved in polyamine metabolism with anxiety disorders. © 2008 Wiley‐Liss, Inc.
Macrophage activation syndrome in patients with systemic juvenile idiopathic arthritis is associated with MUNC13‐4 polymorphisms
Authors: Zhang Kejian , Biroschak Jennifer , Glass David N. , Thompson Susan D. , Finkel Terri , Passo Murray H. , Binstadt Bryce A. , Filipovich Alexandra , Grom Alexei A.
Published: August 2008

Objective

Systemic juvenile idiopathic arthritis (JIA) is associated with macrophage activation syndrome. Macrophage activation syndrome bears a close resemblance to familial hemophagocytic lymphohistiocytosis (HLH). The development of familial HLH has been recently associated with mutations in MUNC13‐4. The purpose of this study was to assess for possible sequence alterations in MUNC13‐4 in patients with systemic JIA/macrophage activation syndrome.

Methods

The MUNC13‐4 sequence was analyzed in 18 unrelated patients with systemic JIA/macrophage activation syndrome, using 32 primer pair sets designed to amplify the 32 exons and at least 100 basepairs of the adjacent intronic regions. DNA samples obtained from 73 unrelated patients with systemic JIA and no history of macrophage activation syndrome and 229 unrelated healthy individuals were used as controls.

Results

The biallelic sequence variants in MUNC13‐4 reported in familial HLH were present in 2 of the 18 patients with JIA/macrophage activation syndrome. Further analysis of the MUNC13‐4 sequences revealed an identical combination of 12 single‐nucleotide polymorphisms (SNPs) in 9 of the remaining 16 patients with systemic JIA/macrophage activation syndrome (56%). Additional analysis suggested that these 12 SNPs (154[−19] g>a, 261[+26] c>g, 388[+81] g>a, 388[+122] c>t, 570[−60] t>g, 888 G>C, 1389[+36] g>a, 1992[+5] g>a, 2447[+144] c>t, 2599 A>G, 2830[+37] c>g, 3198 A>G) were inherited as an extended haplotype. In several patients, in addition to the described haplotype, there were other SNPs in the second allele of MUNC13‐4. Moreover, 1 patient had a complex mutation with 2 changes, 2542 A>C and 2943 G>C, in a cis configuration. The haplotype was present in only 27 (12%) of 229 healthy control subjects (χ2 = 23.5) and in 6 (8.2%) of 73 patients with systemic JIA and no history of macrophage activation syndrome.

Conclusion

The data suggest an association between MUNC13‐4 polymorphisms and macrophage activation syndrome in patients with systemic JIA.
The relationship between plasma microparticles and disease manifestations in patients with systemic sclerosis
Authors: Guiducci Serena , Distler Jörg H. W. , Jüngel Astrid , Huscher Dörte , Huber Lars C. , Michel Beat A. , Gay Renate E. , Pisetsky David S. , Gay Steffen , Matucci‐Cerinic Marco , Distler Oliver
Published: August 2008

Objective

Microparticles are small, membrane‐coated vesicles that can serve as novel signaling structures between cells. The aim of the present study was to analyze the profile of microparticles in the blood of patients with systemic sclerosis (SSc; scleroderma) and healthy controls.

Methods

The study population consisted of 37 patients with SSc and 15 healthy subjects of comparable sex and age. Microparticles were isolated from plasma by high‐speed differential centrifugation. Microparticles were stained with monoclonal antibodies against cell type–specific markers and were quantified by fluorescence‐activated cell sorting analyses.

Results

The total number of microparticles was strongly increased in patients with SSc compared with healthy controls (mean ± SEM 88.0 ± 4.8 × 105 microparticles/ml plasma versus 42.3 ± 9.4 × 105 microparticles/ml plasma; P < 0.001). Similarly, significant increases were found for microparticles derived from platelets, endothelial cells, monocytes, and T cells, reflecting the activation of these cells in SSc. Platelets were the most common source of microparticles in the blood of patients with SSc (66.9 ± 5.2% of all microparticles) and healthy donors, followed by microparticles derived from endothelial cells (8.8 ± 0.9% in SSc patients). The modified Rodnan skin thickness score (MRSS) was inversely correlated with the total number of microparticles. Furthermore, patients with cutaneous ulcers showed a significantly lower total number of microparticles. In multivariate analysis, an additive model of age, C‐reactive protein, MRSS, and subtype of disease accounted for 55% of the variability of the total microparticle count (r = 0.744).

Conclusion

The number of microparticles from different cellular sources is increased in the blood of SSc patients. Considering their role as important mediators of intercellular communication, microparticles could be a novel link between activated cellular compartments in the pathogenesis of SSc.
Increased expression of matrilin‐3 not only in osteoarthritic articular cartilage but also in cartilage‐forming tumors, and down‐regulation of SOX9 via epidermal growth factor domain 1–dependent signaling
Authors: Vincourt Jean‐Baptiste , Vignaud Jean‐Michel , Lionneton Frédéric , Sirveaux François , Kawaki Harumi , Marchal Sophie , Lomazzi Sandra , Plénat François , Guillemin François , Netter Patrick , Takigawa Masaharu , Mainard Didier , Magdalou Jacques
Published: August 2008

Objective

To identify regulators of the cartilaginous phenotype, on the basis of their differential expression in human conventional chondrogenic tumors compared with articular cartilage.

Methods

Differential proteomics analysis revealed matrilin‐3 (MATN3) as a candidate regulator of the cartilaginous phenotype. Its capacity to modulate gene expression was investigated in human HCS‐2/8 chondrosarcoma cells and transfected chondrocytes, using cell culture fractionation, reverse transcription–polymerase chain reaction, and Western blot analyses.

Results

Increased expression of the cartilage‐specific matrix protein MATN3 was specifically observed in enchondromas and conventional chondrosarcomas. A substantial fraction of MATN3 was found in cytoplasmic structures of tumor cells, as demonstrated by immunohistochemistry. Analyses of intracellular MATN3 revealed that it corresponded to an imperfectly maturated MATN3 polypeptide, both in HCS‐2/8 human chondrosarcoma cells and in transfected human chondrocytes. Moderately increased expression of MATN3 resulted in its intracellular retention. Antibody‐mediated blockade of soluble, extracellular MATN3 in HCS‐2/8 cell cultures resulted in increased expression of MATN3 and the chondrogenic transcription factor SOX9. Conversely, increased ectopic expression of MATN3 resulted in decreased expression of MATN3 and SOX9 in primary chondrocytes, while a mutant MATN3 lacking its first epidermal growth factor (EGF)–like domain failed to down‐regulate SOX9.

Conclusion

Aberrant expression and processing of MATN3 are hallmarks of conventional cartilaginous neoplasms. A particular step in the maturation of MATN3 limits its processing through the secretion machinery, resulting in its intracellular accumulation upon increased expression. Soluble, secreted MATN3, however, down‐regulates SOX9 at the messenger RNA and protein levels. The first EGF‐like domain of MATN3 is a critical determinant of its regulatory activity toward SOX9. These activities of MATN3 suggest that its increased expression in osteoarthritis might contribute to the degeneration of articular cartilage.
Promotion of articular cartilage matrix vesicle mineralization by type I collagen
Authors: Jubeck Brian , Gohr Claudia , Fahey Mark , Muth Emily , Matthews Michele , Mattson Eric , Hirschmugl Carol , Rosenthal Ann K.
Published: August 2008

Objective

Calcium pyrophosphate dihydrate (CPPD) and basic calcium phosphate (BCP) crystals occur in up to 60% of osteoarthritic joints and predict an increased severity of arthritis. Articular cartilage vesicles (ACVs) generate CPPD crystals in the presence of ATP and BCP crystals with added β‐glycerophosphate. While ACVs are present in normal articular cartilage, they mineralize primarily in cartilage from osteoarthritic joints. The aim of this study was to explore the hypothesis that ACV mineralization is regulated by components of the surrounding extracellular matrix.

Methods

Porcine ACVs were embedded in agarose gels containing type II and/or type I collagen and/or proteoglycans. Mineralization was measured as 45Ca accumulation stimulated by ATP or β‐glycerophosphate and reflects both nucleation and growth. Synthetic CPPD and BCP crystals were embedded in similar gels to isolate the effect of matrix components on crystal growth.

Results

After establishing baseline responsiveness of ACVs to ATP and β‐glycerophosphate in agarose gels, we examined the ability of ATP and β‐glycerophosphate to stimulate mineral formation in gels containing various matrix components. Type II collagen suppressed the ability of ATP to stimulate mineralization, while a combination of type II plus type I collagen increased the effect of ATP and β‐glycerophosphate on mineralization. Type I collagen affected ACV mineralization in a dose‐responsive manner. Neither type of collagen significantly affected crystal growth or levels of mineralization‐regulating enzymes. Proteoglycans suppressed mineral formation by ACVs in gels containing both type I and type II collagen.

Conclusion

Cartilage matrix changes that occur with osteoarthritis, such as increased quantities of type I collagen and reduced proteoglycan levels, may promote ACV mineralization.
Chronic arthritis aggravates vascular lesions in rabbits with atherosclerosis: A novel model of atherosclerosis associated with chronic inflammation
Authors: Largo Raquel , Sánchez‐Pernaute Olga , Marcos M. Esther , Moreno‐Rubio Juan , Aparicio César , Granado Rosario , Ortega Luis , Egido Jesús , Herrero‐Beaumont Gabriel
Published: August 2008

Objective

To determine whether systemic inflammation induced by chronic antigen‐induced arthritis (AIA) accelerates vascular lesions in rabbits with atherosclerosis.

Methods

Two models of atherosclerosis and chronic AIA were combined. Atherosclerosis was induced by coupling a hyperlipemic diet with an endothelial lesion at the femoral arteries, while chronic AIA was induced by ovalbumin injection. Markers in sera and peripheral blood mononuclear cells (PBMCs) as well as vessels and synovial membranes from the rabbits with the double phenotype (both chronic AIA and atherosclerosis) were compared with those from rabbits with each disease alone.

Results

Serum levels of interleukin‐6, C‐reactive protein, and prostaglandin E2 increased in rabbits with both chronic AIA and atherosclerosis as compared with healthy animals or animals with either chronic AIA alone or atherosclerosis alone. NF‐κB binding and CCL2 and cyclooxygenase 2 (COX‐2) expression were higher in PBMCs from rabbits with both chronic AIA and atherosclerosis than in PBMCs from healthy rabbits. The intima‐media thickness ratio of femoral arteries was equally increased in rabbits with atherosclerosis alone and in rabbits with both chronic AIA and atherosclerosis, but the latter group showed a higher level of macrophage infiltration. Femoral CCL2 and COX‐2 expression was increased in rabbits with both chronic AIA and atherosclerosis as compared with rabbits with atherosclerosis alone. In the aortas, vascular lesions were found in 27% of rabbits with atherosclerosis alone and in 60% of rabbits with both chronic AIA and atherosclerosis. Rabbits with both chronic AIA and atherosclerosis exhibited more severe synovitis and higher synovial expression of CCL2 than did rabbits with chronic AIA alone.

Conclusion

The onset of chronic AIA in animals with atherosclerosis resulted in the local and systemic up‐regulation of mediators of tissue inflammation and plaque instability associated with a higher incidence of aortic lesions. This model could represent a novel approach to the study of inflammation‐associated atherosclerosis.
Remission and rheumatoid arthritis: Data on patients receiving usual care in twenty‐four countries
Authors: Sokka Tuulikki , Hetland Merete Lund , Mäkinen Heidi , Kautiainen Hannu , Hørslev‐Petersen Kim , Luukkainen Reijo K. , Combe Bernard , Badsha Humeira , Drosos Alexandros A. , Devlin Joe , Ferraccioli Gianfranco , Morelli Alessia , Hoekstra Monique , Majdan Maria , Sadkiewicz Stefan , Belmonte Miguel , Holmqvist Ann‐Carin , Choy Ernest , Burmester Gerd R. , Tunc Recep , Dimić Aleksander , Nedović Jovan , Stanković Aleksandra , Bergman Martin , Toloza Sergio , Pincus Theodore ,   Questionnaires in Standard Monitoring of Patients With Rheumatoid Arthritis Group
Published: August 2008

Objective

To compare the performance of different definitions of remission in a large multinational cross‐sectional cohort of patients with rheumatoid arthritis (RA).

Methods

The Questionnaires in Standard Monitoring of Patients with RA (QUEST‐RA) database, which (as of January 2008) included 5,848 patients receiving usual care at 67 sites in 24 countries, was used for this study. Patients were clinically assessed by rheumatologists and completed a 4‐page self‐report questionnaire. The database was analyzed according to the following definitions of remission: American College of Rheumatology (ACR) definition, Disease Activity Score in 28 joints (DAS28), Clinical Disease Activity Index (CDAI), clinical remission assessed using 42 and 28 joints (Clin42 and Clin28), patient self‐report Routine Assessment of Patient Index Data 3 (RAPID3), and physician report of no disease activity (MD remission).

Results

The overall remission rate was lowest using the ACR definition of remission (8.6%), followed by the Clin42 (10.6%), Clin28 (12.6%), CDAI (13.8%), MD remission (14.2%), and RAPID3 (14.3%); the rate of remission was highest when remission was defined using the DAS28 (19.6%). The difference between the highest and lowest remission rates was ≥15% in 10 countries, 5–14% in 7 countries, and <5% in 7 countries (the latter of which had generally low remission rates [<5.5%]). Regardless of the definition of remission, male sex, higher education, shorter disease duration, smaller number of comorbidities, and regular exercise were statistically significantly associated with remission.

Conclusion

The use of different definitions of RA remission leads to different results with regard to remission rates, with considerable variation among countries and between sexes. Reported remission rates in clinical trials and clinical studies have to be interpreted in light of the definition of remission that has been used.
Tibial subchondral trabecular volumetric bone density in medial knee joint osteoarthritis using peripheral quantitative computed tomography technology
Authors: Bennell Kim L. , Creaby Mark W. , Wrigley Tim V. , Hunter David J.
Published: August 2008

Objective

Knee osteoarthritis (OA) is an organ‐level failure of the joint involving pathologic changes in articular cartilage and bone. This cross‐sectional study compared apparent volumetric bone mineral density (vBMD) of proximal tibial subchondral trabecular bone in people with and without knee OA, using peripheral quantitative computed tomography (pQCT).

Methods

Seventy‐five individuals with mild or moderate medial compartment knee OA and 41 asymptomatic controls were recruited. Peripheral QCT was used to measure vBMD of trabecular bone beneath medial and lateral tibiofemoral compartments at levels of 2% and 4% of tibial length, distal to the tibial plateau.

Results

There was no significant difference in vBMD beneath the overall medial and lateral compartments between the 3 groups. However, in the affected medial compartment of those with moderate OA, lower vBMD was seen in the 2 posterior subregions compared with controls and those with mild knee OA, while higher vBMD was seen in the anteromedial subregion. Beneath the unaffected or lesser affected lateral compartment, significantly lower vBMD was seen at the 2% level in the anterior and lateral subregions of those with moderate disease. Volumetric BMD ratios showed relatively higher vBMD in the medial compartment compared with the lateral compartment, but these ratios were not influenced by disease status.

Conclusion

Subregional vBMD changes were evident beneath the medial and lateral compartments of those with moderate medial knee OA. Of import, the posterior subchondral trabecular regions of the medial tibial plateau have markedly lower vBMD.
Rho kinase–dependent CCL20 induced by dynamic compression of human chondrocytes
Authors: Haudenschild Dominik R. , Nguyen Bao , Chen Jianfen , D'Lima Darryl D. , Lotz Martin K.
Published: August 2008

Objective

Mechanical stimulation of cartilage affects tissue homeostasis and chondrocyte function. The chondrocyte phenotype is dependent on cell shape, which is largely determined by the actin cytoskeleton. Reorganization of the actin cytoskeleton results from Rho GTPase activation. The purpose of this study was to examine the roles of both actin and Rho in mechanotransduction in chondrocytes.

Methods

We embedded human articular chondrocytes in 2 × 6–mm agarose discs at 5 × 106 cells/ml and subjected the discs to unconfined dynamic compression at 0.5 Hz. By comparing samples with and without dynamic compression, we identified Rho activation according to the GTP‐bound active RhoA measured in cell lysates. We identified rearrangements in filamentous actin structures using fluorescence‐labeled phalloidin and confocal microscopy of fixed samples. We identified altered gene expression using TaqMan quantitative reverse transcription–polymerase chain reaction analysis. We tested for a requirement for Rho signaling by performing the dynamic compression in the presence of Rho kinase inhibitors.

Results

RhoA activation occurred within 5–10 minutes of dynamic compression. Rho kinase–dependent actin reorganization occurred within 20 minutes after application of dynamic compression and was apparent as “punctate” F‐actin structures that were visible under confocal microscopy. We identified early‐phase mechanoresponsive genes (CCL20 and inducible nitric oxide synthase) that were highly up‐regulated within 1 hour of dynamic compression in a Rho kinase–dependent and actin‐dependent manner.

Conclusion

Together, these results are the first demonstration that the Rho–Rho kinase pathway and actin cytoskeletal reorganization are required for changes in the expression of genes involved in human chondrocyte mechanotransduction.
The presentation and outcome of heart failure in patients with rheumatoid arthritis differs from that in the general population
Authors: Davis John M. , Roger Véronique L. , Crowson Cynthia S. , Kremers Hilal Maradit , Therneau Terry M. , Gabriel Sherine E.
Published: August 2008

Objective

To compare the clinical presentation, management, and outcome of heart failure in patients with rheumatoid arthritis (RA) compared with non‐RA patients.

Methods

We conducted a community‐based cohort study in the setting of Olmsted County, Minnesota, from 1979 to 2000. One hundred three patients with RA and 852 non‐RA patients with incident heart failure (physician diagnosed and Framingham criteria validated) were compared. Age‐ and sex‐adjusted rates/frequencies and multivariable logistic regression models were used to compare the clinical features and mortality of heart failure following its onset in the 2 groups of patients.

Results

The patients with RA were more often female and less frequently were obese, were hypertensive, or had ischemic heart disease. Patients with RA and heart failure had fewer typical symptoms and signs and were less likely to undergo echocardiography compared with non‐RA patients. After adjusting for differences, the patients with RA and heart failure were more likely to have preserved ejection fraction (≥50%). Mortality at 1 year following heart failure was higher in patients with RA compared with non‐RA patients (35% versus 19%; multivariable hazard ratio 1.89, 95% confidence interval 1.26–2.84).

Conclusion

Both the clinical presentation and the outcome of heart failure differ significantly between patients with and those without RA from the same population. Among patients with RA, the presentation of heart failure is more subtle, myocardial function is more likely preserved, while mortality from heart failure is significantly higher. These findings emphasize the importance of more vigilant screening of patients with RA for early signs of heart failure and may represent important insights into the biologic mechanisms underlying heart failure in RA.