bluuebunny/crossref_metadata_2025 huggingface dataset:
Functional variation among mesenchymal stem cells derived from different tissue sources
Authors: Yi Ning , Zeng Qiao , Zheng Chunbing , Li Shiping , Lv Bo , Wang Cheng , Li Chanyi , Jiang Wenjiao , Liu Yun , Yang Yuan , Yan Tenglong , Xue Jinfeng , Xue Zhigang
Published: June 2024

Background

Mesenchymal stem cells (MSCs) are increasingly recognized for their regenerative potential. However, their clinical application is hindered by their inherent variability, which is influenced by various factors, such as the tissue source, culture conditions, and passage number.

Methods

MSCs were sourced from clinically relevant tissues, including adipose tissue-derived MSCs (ADMSCs, n = 2), chorionic villi-derived MSCs (CMMSCs, n = 2), amniotic membrane-derived MSCs (AMMSCs, n = 3), and umbilical cord-derived MSCs (UCMSCs, n = 3). Passages included the umbilical cord at P0 (UCMSCP0, n = 2), P3 (UCMSCP3, n = 2), and P5 (UCMSCP5, n = 2) as well as the umbilical cord at P5 cultured under low-oxygen conditions (UCMSCP5L, n = 2).

Results

We observed that MSCs from different tissue origins clustered into six distinct functional subpopulations, each with varying proportions. Notably, ADMSCs exhibited a higher proportion of subpopulations associated with vascular regeneration, suggesting that they are beneficial for applications in vascular regeneration. Additionally, CMMSCs had a high proportion of subpopulations associated with reproductive processes. UCMSCP5 and UCMSCP5L had higher proportions of subpopulations related to female reproductive function than those for earlier passages. Furthermore, UCMSCP5L, cultured under low-oxygen (hypoxic) conditions, had a high proportion of subpopulations associated with pro-angiogenic characteristics, with implications for optimizing vascular regeneration.

Conclusions

This study revealed variation in the distribution of MSC subpopulations among different tissue sources, passages, and culture conditions, including differences in functions related to vascular and reproductive system regeneration. These findings hold promise for personalized regenerative medicine and may lead to more effective clinical treatments across a spectrum of medical conditions.
ULK2 suppresses ovarian cancer cell migration and invasion by elevating IGFBP3
Authors: Chen Xiaoxi , Shao Changxiang , Liu Jing , Sun Huizhen , Yao Bingyi , Ma Chengbin , Xu Han , Zhu Weipei
Published: June 2024

Background

Ovarian cancer is an aggressive malignancy with high mortality known for its considerable metastatic potential. This study aimed to explore the expression and functional role of Unc-51 like autophagy activating kinase 2 (ULK2) in the progression of ovarian cancer.

Methods

ULK2 expression patterns in ovarian cancer tissues as well as benign tumor control samples obtained from our institution were evaluated using immunohistochemistry. Cell counting kit 8 and Transwell assays were applied to assess the effects of ULK2 overexpression on cell proliferation, migration and invasion, respectively. RNA sequencing was performed to explore potential mechanisms of action of ULK2 beyond its classical autophagy modulation.

Results

Our experiments showed significant downregulation of ULK2 in ovarian cancer tissues. Importantly, low expression of ULK2 was markedly correlated with decreased overall survival. In vitro functional studies further demonstrated that overexpression of ULK2 significantly suppressed tumor cell proliferation, migration, and invasion. RNA sequencing analysis revealed a potential regulatory role of ULK2 in the insulin signaling pathway through upregulation of insulin-like growth factor binding protein-3 (IGFBP3) in ovarian cancer cells.

Conclusions

In summary, the collective data indicated that ULK2 acted as a tumor suppressor in ovarian cancer by upregulating the expression of IGFBP3. Our study underscores the potential utility of ULK2 as a valuable prognostic marker for ovarian cancer.
Food addiction and the physical and mental health status of adults with overweight and obesity
Authors: Zielińska Magdalena , Łuszczki Edyta , Szymańska Anna , Dereń Katarzyna
Published: June 2024

Background

Overweight and obesity now affect more than a third of the world’s population. They are strongly associated with somatic diseases, in particular increasing the risk of many metabolic and cardiovascular diseases, but also with mental disorders. In particular, there is a strong association between obesity and depression. As a result, more attention is paid to the neurobiological, behavioural, and psychological mechanisms involved in eating. One of these is food addiction (FA). Research comparing lifestyle elements, physical and mental health problems of excess body weight and individuals with FA is limited and has focused on younger people, mainly students. There is also a lack of studies that relate actual metabolic parameters to FA. To better understand the problem of FA also in older adults, it is important to understand the specific relationships between these variables.

Methods

A cross-sectional survey was conducted with 172 adults with overweight and obesity (82% female) aged 23–85 years. The mean age of all subjects was M = 59.97 years (SD = 11.93), the mean BMI was M = 32.05 kg/m2 (SD = 4.84), and the mean body fat was M = 39.12% (SD = 6.48). The following questionnaires were used: Food Frequency Questionnaire-6 (FFQ-6), Global Physical Activity Questionnaire (GPAQ), Three Factor Eating Questionnaire-R18 (TFEQ-R18), Yale Food Addiction Scale 2. 0 (YFAS 2.0), Zung Self-Rating Depression Scale (SDS). Body composition, anthropometry, fasting glucose, lipid profile, and blood pressure were measured.

Results

A total of 22.7% of participants with overweight and obesity had symptoms of depression according to the SDS, and 18.6% met the criteria for FA according to YFAS 2.0. FA was statistically significantly more common among people up to 50 years. BMI, body fat mass, diastolic blood pressure and sedentary behaviour were statistically significantly higher in people with FA symptoms. Those who were sedentary for 301–450 min per day were significantly more likely to have depressive symptoms, and those who were sedentary for more than 450 min per day were significantly more likely to have FA symptoms.

Conclusions

Our findings complement the current literature on FA, particularly in older adults and metabolic parameters, and suggest further research directions. Although our cross-sectional study design does not allow causal interpretations, increasing physical activity appears to be particularly important in the management of people with overweight or obesity and FA. This may be even more important than for people with depression alone, but future research is needed to explore these relationships further.
A review of predator exclusion fencing to create mainland islands in Hawaiʻi
Authors: Young Lindsay , VanderWerf Eric
Published: June 2024

Background

Invasive species are the primary threat to island ecosystems globally and are responsible for approximately two-thirds of all island species extinctions in the past 400 years. Non-native mammals—primarily rats, cats, mongooses, goats, sheep, and pigs—have had devastating impacts on at-risk species and are major factors in population declines and extinctions in Hawaiʻi. With the development of fencing technology that can exclude all mammalian predators, the focus for some locations in Hawaiʻi shifted from predator control to local eradication.

Methods

This article describes all existing and planned full predator exclusion fences in Hawaiʻi by documenting the size and design of each fence, the outcomes the predator eradications, maintenance issues at each fence, and the resulting native species responses.

Results

Twelve predator exclusion fences were constructed in the Hawaiian Islands from 2011–2023 and six more were planned or under construction; all were for the protection of native seabirds and waterbirds. Fences ranged in length from 304–4,877 m and enclosed 1.2–640 ha. One-third of the 18 fences were peninsula-style with open ends; the remaining two-thirds of the fences were complete enclosures. The purpose of twelve of the fences (67%) was to protect existing bird populations, and six (33%) were initiated for mitigation required under the U.S. Endangered Species Act. Of the six mitigation fences, 83% were for the social attraction of seabirds and one fence was for translocation of seabirds; none of the mitigation fences protected existing bird populations. Rats and mice were present in every predator exclusion fence site; mice were eradicated from five of six sites (83%) where they were targeted and rats (three species) were eradicated from eight of 11 sites (72%). Mongoose, cats, pigs, and deer were eradicated from every site where they were targeted. Predator incursions occurred in every fence. Rat and mouse incursions were in many cases chronic or complete reinvasions, but cat and mongoose incursions were occasional and depended on fence type (i.e., enclosed vs. peninsula). The advent of predator exclusion fencing has resulted in great gains for protecting existing seabirds and waterbirds, which demonstrated dramatic increases in reproductive success and colony growth. With threats from invasive species expected to increase in the future, predator exclusion fencing will become an increasingly important tool in protecting island species.
Serum Magnesium Levels and Lipid Profile in Patients with Epileptic Seizures: A Cross-sectional Study
Authors: Agrawal Monika , Sharma Shalu , Goyal Astha , Shinde Sarita A
Published: June 2024

Introduction: Recurrent seizures of cerebral origin with episodes of sensory, motor, or autonomic expression, with or without loss of consciousness, are typical symptoms of epilepsy, a chronic neurological condition. As a voltage-dependent calcium channel antagonist, magnesium inhibits calcium ion release, which reduces neuronal excitability in hypomagnesemia. It is well recognised that the most frequently prescribed Antiepileptic Drugs (AEDs), namely carbamazepine, phenytoin, and phenobarbital, have adverse effects on lipid profiles. Aim: To compare the levels of serum magnesium and serum lipid profiles in patients with epileptic seizures and healthy controls. Materials and Methods: The present cross-sectional study included 50 clinically diagnosed patients with epileptic seizures, aged between 18-60 years, and 50 age and sexmatched healthy controls visiting the Department of Neurology, Mahatma Gandhi Medical College (MGMC), Jaipur, Rajasthan, India from October 2019 to March 2020. A 5 mL venous blood sample was collected for biochemical investigations such as serum magnesium, serum Total Cholesterol (TC), serum Triglycerides (TG), serum High Density Lipoprotein cholesterol (HDL-C), serum Low Density Lipoprotein cholesterol (LDL-C), and serum Very Low Density Lipoprotein cholesterol (VLDL-C) and assayed. Student’s t-test was applied, and a p-value of <0.05 was considered statistically significant. Results: In the present study, epileptic cases (n=50) included 35 male patients and 15 female patients with a mean age of 36.1±15.56 years, and healthy controls (n=50) included 37 male patients and 13 female patients with a mean age of 38.26±8.54 years. When compared to healthy controls, patients with epileptic seizures had lower serum magnesium levels with mean values of 4.18±1.22 and 2.12±1.00, respectively (p-value ≤0.001). Patients with epileptic seizures had higher values of the serum lipid profile, i.e., serum TG, TC, low-density lipoprotein cholesterol, and very low-density lipoprotein cholesterol than healthy controls with a p-value ≤0.001, which is statistically significant. On the contrary, serum HDL-C levels in epileptic patients (43.68±7.37 mg/dL) are lower than healthy controls (49.69±5.73 mg/dL). Conclusion: Correcting the serum magnesium levels in people with epileptic seizures may help reduce the intensity of the seizures.
Adverse Event Profile and Compliance of Docetaxel with Radiation in Cisplatin-Ineligible Patients of Locally Advanced Head and Neck Squamous Cell Carcinoma: A Research Protocol
Authors: Kaushik Himanshi , Dongre Amol
Published: June 2024

Introduction: Concomitant chemoradiation with cisplatin is standard treatment for non-metastatic head and neck cancers, but often limited by toxicities, especially deranged renal function and hearing complications. This leads to limited cycles of cisplatin due to challenges in administration and is not suitable for patients with poor renal function and hearing issues. Need of the study: Not enough data is available for patients who are not suitable for cisplatin administration along with radiation either due to sensitivity to cisplatin or the adverse effects mentioned earlier. Docetaxel has been recently observed to benefit such patients in overall response outcome including Disease Free Survival (DFS) and Overall Survival (OS) when administered concurrently with radiation. Improved clinical response with minimal toxicity to normal tissue is seen with docetaxel, as it is a phase-specific agent. Therefore, this would be a good alternative to Cisplatin in patients with deranged kidney function and sensorineural hearing loss. Aim: To estimate the adverse event profile and compliance of docetaxel with radiation. Methodology: This prospective observational study will be conducted in the department of Medical Oncology and Radiation Oncology at Sidharth Gupta Memorial Cancer Hospital, Datta Meghe Institute of Medical Sciences, Sawangi (M), Wardha, Maharashtra, India, starting from May 2024 to May 2025. Patients with pathologically confirmed non-metastatic Head and Neck Squamous Cell Carcinoma (HNSCC), who are planned for Concurrent Chemoradiation (CCRT) but not suitable for cisplatin, will receive concurrent weekly docetaxel at a dose of 15 mg/sqm. Radiotherapy (RT) will be delivered according to the institutional protocol, daily dose of 200 cGy for five days a week will be given. Continuous monitoring during treatment will include weekly clinical evaluations, regular blood tests (haemoglobin, blood counts, renal functions), and grading of adverse events (CTCAE v5 criteria). Treatment response will be assessed via clinical evaluation and CECT scans (RECIST v1.1). Statistical analysis will be performed using Statistical Package for Social Sciences (SPSS) version 26.0 and will involve analysis of categorical variables with Chi-square and Fisher-exact tests, and continuous variables with unpaired t-tests and Analysis of Variance (ANOVA). Time to event analysis will be done using the Kaplan-Meier method with p-value <0.05 considered significant.
Influencing Drivers of Agricultural Production Technology of Rice in Burundi
Authors: W.M. Ndayitwayeko , D. Mpawenimana , J. Bigirimana
Published: June 2024

The adoption of agricultural technologies has become the key to limiting imports and meeting Burundi's rice food needs. This is because rice production is generally low in the country due to the ever-increasing population. This study identified the constraints of rice production, assessed the rate and identified the determinants of the adoption of the rutete rice variety. Primary data was collected using the well-structured questionnaire from 524 rice farmers who were selected using a simple random sampling in the study area. Data analysis was performed using Kendall's tau coefficient for constraints, probit for adoption rate and Heckman's sample selection model for determinants. According to the results, the insufficiency or delay in the supply of fertilizers, the problem of water availability and the problem of access to agricultural credit are the major constraints of rice production. They also show that 29% of respondents have adopted the rutete rice variety. Furthermore, the results show that sex, level of education, planted area, access to extension services, membership in an association and possession of a mobile phone are the determinants of the adoption of the variety of rice rutete. It is therefore recommended that farmers in the study area be encouraged to adopt the rutete rice variety. We also recommend that the government subsidize agricultural inputs and put in place a policy of loosen the tax burden to the microfinance so that the cost of access agricultural credit for rice farmers is lowered. This will prompt an increase of production. Rice farmers who are not members in the farmer-associations should be sensitized to participate.
The Relationship between Academic Mindset and Academic Performance: A Case of Gedu College of Business Studies, Bhutan
Authors: Wangmo Sonam , Wangpo Kinga
Published: June 2024

Aims: This study attempted to assess how students’ academic mindset influences their academic performance and secondly, whether academic mindset differ across demographic variables like gender. Four academic mindset factors were examined by the researchers.
Study Design: A quantitative research design with a descriptive study was used in this study.  
Place and Duration of Study: The study was conducted in Bhutan for a period of one year.
Methodology: A total of 314 students from Gedu College of Business studies of Bhutan participated in the study using an online structured questionnaire developed by the researchers and shared through Google Forms. Simple random sampling technique was employed to draw the samples from the given population. The results were analyzed and presented using regression analysis and independent T-Test.
Results: According to the findings, there is a positive relationship between variables of academic mindset such as self-efficacy and growth mindset with academic performance. Secondly, in terms of gender, there is difference in terms of view on the self-efficacy variable. 
Conclusion: The key recommendations of the study is for intervention from academic institutions to help students develop a growth mindset and also improve the self-efficacy of the students to draw better academic results.
Study of Management Practices of Bacteremia in a Referral Service in Dakar, Senegal (2018–2022)
Authors: Thioub Daouda , Sokoba Zénab Malika , Mbaye Khardiata Diallo , Lakhe Ndèye Aissatou , Badiane Aboubakar Sidikh , Fall Ndèye Maguette , Ka Daye , Cisse Viviane Marie Pierre , Seydi Moussa
Published: June 2024

Introduction: bacteremia remains a public health problem worldwide. Unfortunately, none of the studies carried out on this subject in our context has looked at how bacteremia is managed. We therefore undertook this study to assess the management practices of bacteremia at the infectious and Tropical diseases department.
Methods: this was a retrospective and descriptive study based on the analysis of records of patients hospitalized at Infectious and Tropical diseases department of Fann national university hospital in Dakar, Senegal. This study covered a five-year period, extending from January 1st 2018, to December 31 2022.
Results: During our study period, 213 patients were enrolled. The sex ratio was 1.13. The average age was 45.6 ± 17.5 years. Most patients (63.4%) had at least one comorbidity. Thirty-two percent (32%) had a history of recent hospitalization, and 25% had received recent antibiotic therapy. During the study period, 231 bacterial strains were isolated. Gram-positive cocci accounted for 68%, and Gram-negative bacilli for 32%. The main bacteria isolated were Staphylococcus aureus (30.3%). Empiric antibiotic therapy had been initiated in 81% of patients. Following antibiotic susceptibility testing, 61% of patients had their antibiotic therapy readjusted. In 61% of cases, the therapeutic protocol was deemed unsuitable, in line with the recommendations of Senegal's national antibiotic guide and international recommendations.
Conclusion: Bacteremias are common infections with significant morbidity and mortality that require a thorough understanding to improve management strategies and reduce AMR. In our context of low-income countries, following treatment guidelines is key to reducing AMR.
Influence of Tillage Methods, Farmyard Manure and Potassium Rates on Soil Moisture and Relationship with Cassava Root Yields in Kagera, Tanzania
Authors: Merumba Mgeta Steven , Semoka Johnson Mashambo , Semu Ernest , Msanya Balthazar Michael , Blandes Joyce Siima
Published: June 2024

Field experimental trial was established in Biharamulo, Bukoba and Missenyi districts, Tanzania in two consecutive (2018/19 and 2019/20) cropping seasons, aimed at determining the effects of tillage methods, farmyard manure (FYM) and potassium rates on soil moisture conservation and the relationship between soil moisture and cassava root yield using the split-plot design with three replications. Treatments: Tillage methods (flat tillage, open ridging and tie ridging) as the main plots and; the fertilizer rates [farmyard manure alone at 4 MT ha-1 or FYM alone at 8 MT ha-1, nitrogen (40 kg N ha-1) + phosphorus (30 kg P ha-1) + potassium at 40, 80 or 120 kg K ha-1 and the combination of FYM at 4 or 8 MT ha-1 + potassium at 40, 80 or 120 kg K ha-1] and the control as the sub-plots were arranged in Randomized Complete Block Designed (RCBD). Farmyard manure was applied at planting and inorganic fertilizers were applied in two splits. Soil moisture was monitored starting from one week after the last rain event at an interval of two weeks up to the first rain event of the following season. Soil moisture samples (0 - 30 cm) were collected from the rows and ridges using a soil auger, placed in cores, weighed, oven-dried at 105 oC and reweighed after 24 hours to constant weight. The soil moisture content (%) in each soil sample was determined gravimetrically. Cassava root yields were recorded from each treatment during harvesting. The results indicated that the use of ridges conserved significantly (P < .001) more soil moisture (24 - 58%) than the use of flat tillage (7 - 27%) in both cropping seasons. The use of tie ridges conserved significantly (P ≤ .01) more soil moisture (11 - 58%) than the use of open ridges (10 - 57%) in the medium and high rainfall areas as opposed to the low rainfall area, which both conserved similar soil moisture. There was a significant (P < .001) difference in soil moisture conservation between the control and fertilizer types and rates. The use of FYM conserved significantly (P < .001) more soil moistures (16.54 - 63.48%) than the combined use of inorganic N, P and K fertilizer rates (12.27 - 53.60%). The use of FYM at 8 MT ha-1 conserved significantly (P < .001) more soil moisture (19.94 - 62.16%) than FYM at 4 MT ha-1 (16.80 - 58.33%). However, there was no significant (P = .33) different in soil moisture conservation between the combined use of inorganic N, P and K fertilizers and; the control. Results from regression analysis indicated significant (P < .001) association between soil moisture conservation and changes in cassava root yields. Thus, planting cassava on ridges, concurrently with the application of FYM at 8 MT ha-1 is recommended for adequate soil moisture conservation and increasing cassava root yield.
Understanding Heat Stress and Tolerance Mechanisms in Wheat (Triticum aestivum L.): A Comprehensive Review
Authors: Maity Souvik , Shrivastav Shiv Prakash
Published: June 2024

Wheat (Triticum aestivum L.), a vital cereal crop in the Poaceae family, plays a crucial role in global agriculture. It contributes approximately 30% of the world's grain production and constitutes half of the grain traded internationally. Serving as a staple food in over 40 countries, wheat provides essential calories to 85% of the global population and protein to 82%. With the global population expected to reach 9.1 billion by 2050, the Food and Agriculture Organization (FAO) projects that nearly one billion additional tons of cereal will be needed annually to meet increasing demand. Enhancing wheat productivity and production is thus essential. Wheat is cultivated in tropical and subtropical regions, where it faces various abiotic stresses that significantly impact yield, with heat and drought being the most critical challenges. Global climate models predict a potential increase in mean ambient temperature by up to 6°C by the end of the century. Wheat is highly sensitive to heat stress; even a 1°C rise in temperature can reduce global wheat production by 6%. Heat stress affects wheat's physiological, biological, and biochemical processes, including seed germination, grain filling duration, grain number, Rubisco enzyme activity, photosynthetic capacity, assimilate translocation rate, leaf senescence, chlorophyll content, and overall yield. To combat heat stress, wheat has developed diverse tolerance mechanisms. These include the induction of heat shock proteins (HSPs) that assist in proper protein folding and the activation of an antioxidative defense system to detoxify reactive oxygen species (ROS). Traits like Stay Green (SG), chlorophyll fluorescence, and canopy temperature are closely linked to heat tolerance. Understanding and improving these mechanisms are imperative to sustain and enhance wheat production to meet future food demands amidst global climate changes. This review provides a comprehensive analysis of the effects of heat stress on wheat morphology, physiology, and biochemistry. It also discusses the mechanisms of heat tolerance, emphasizing the importance of developing crop varieties capable of withstanding future climatic conditions. Understanding these mechanisms at physiological, biochemical, and morphological levels is crucial for ensuring future food security.
Transformation of Phosphorus Fractions in Various Soil Types of Kerala: An Incubation Study
Authors: John Asha Grace , M. R. Reshma , V. I. Beena , C. Santhosh , M. Sajitha Vijayan
Published: June 2024

Aims: Research study was undertaken to examine the dynamic changes and transformations of applied phosphorus (P) in soil, spanning a comprehensive period of 75 days, to understand its interactions and potential impact on nutrient availability.
Study Design: Factorial CRD.
Place and Duration of Study: Department of Soil Science and Agricultural Chemistry, Vellanikkara, Thrissur, between September 2023 and December 2023.
Methodology: Soil samples collected from three different agroecological units (AEU) of Kerala varying in physicochemical properties were selected for the study Plastic containers filled with 300g of processed soil were treated with four levels of phosphorus as KH2PO4, with three replications for each treatment. The experiment was laid under factorial completely randomized design (CRD). On 15th, 45th and 75th day, each treatment combinations were analysed for pH, Electrical conductivity (EC), Available P (Av. P) and different fractions of phosphorus viz. Saloid-bound P (SB-P), Aluminum phosphate (Al-P), Iron phosphate (Fe-P), Reductant soluble phosphate (RS-P), Calcium phosphate (Ca-P) and Organic P (OP).
Results: Soil types had significant influence on pH, electrical conductivity, available phosphorus and various phosphorus fractions. The levels of phosphorus had significant influence on pH, EC, Av. P and phosphorus fractions except RS-P. Incubation period had significant effect on EC, Av. P and all phosphorus fractions but did not influence pH. The interaction among soil type, phosphorus levels and incubation period did not have significant influence on pH, available P and RS-P. Formation of Fe-P and Al-P was found highest on 15th day.
Conclusion: EC, SB-P, OP was found to be highest on 75th day of incubation due to the slow dissolution, desorption as well as immobilisation and mineralisation reactions in the soil. The rapid precipitation of available phosphorus as Fe and Al phosphates reduces the likelihood of RS-P formation. Due to slow diffusion of P into sesquioxide, the highest value of RS-P was recorded on 75th day of incubation. It was also notable that RS-P was not influenced by the level of P. Ca-P formation was found lowest in Kuttanad soil due to ultra-acidic condition.
The NCTC 2544 IL‐18 Assay for the In Vitro Identification of Contact Allergens
Authors: Galbiati Valentina , Corsini Emanuela
Published: November 2012

Assessment of allergenic potency of low‐molecular‐weight compounds is generally performed using animal models, such as the murine Local Lymph Node Assay (LLNA) and the Guinea Pig Maximization Test (GMT). Progress in understanding the mechanism of skin sensitization, including effects on the production of cytokines by different cell types within the skin, provides the opportunity to develop in vitro tests as an alternative to in vivo sensitization testing. This unit will describe a method for differentiating contact allergens from low‐molecular‐weight respiratory allergens and irritants, based on the selective induction of intracellular interleukin 18 (IL‐18) in the human keratinocyte cell line NCTC 2544. Similar results could also be obtained using primary human keratinocytes or other human keratinocyte cell lines, e.g., HaCaT, HPKII, etc. IL‐18 was chosen because this cytokine has been demonstrated to favor Th‐1‐type immune responses by enhancing the secretion of pro‐inflammatory mediators such as TNF‐α, IL‐8, and IFN‐γ, and to play a key proximal role in the induction of allergic contact dermatitis. Curr. Protoc. Toxicol. 54:20.8.1‐20.8.18. © 2012 by John Wiley & Sons, Inc.
Membrane Vesicle ABC Transporter Assays for Drug Safety Assessment
Authors: van Staden Carlo J. , Morgan Ryan E. , Ramachandran Bharath , Chen Yuan , Lee Paul H. , Hamadeh Hisham K.
Published: November 2012

The use of plasma membrane vesicles that overexpress the bile salt export pump (BSEP) or multidrug resistance−associated protein 2, 3, or 4 (MRP2‐4) with an in vitro vacuum filtration system offers a rapid and reliable means for screening drug candidates for their effects on transporter function in hepatocytes and thus their potential for causing drug‐induced liver injury (DILI). Comparison of transporter activity in the presence and absence of ATP allows for determination of a specific assay window for each transporter. This window is used to determine the degree to which each test compound inhibits transporter activity. This assay battery is helpful for prioritizing and rank‐ordering compounds within a chemical series with respect to each other and in the context of known inhibitors of transporter activity and/or liver injury. This model can be used to influence the drug development process at an early stage and provide rapid feedback regarding the selection of compounds for advancement to in vivo safety evaluations. A detailed protocol for the high‐throughput assessment of ABC transporter function is provided, including specific recommendations for curve‐fitting to help ensure consistent results. Curr. Protoc. Toxicol. 54:23.5.1‐23.5.24. © 2012 by John Wiley & Sons, Inc.
Association of herbal cannabis use with negative psychosocial parameters in patients with fibromyalgia
Authors: Ste‐Marie Peter A. , Fitzcharles Mary‐Ann , Gamsa Ann , Ware Mark A. , Shir Yoram
Published: November 2012

Objective

Patients with chronic pain, including fibromyalgia (FM), may seek treatments outside of mainstream medicine. Medicinal cannabinoids are popularly advocated for pain relief but with limited evidence for efficacy in FM. The extent of use of cannabinoids in FM is unknown.

Methods

We have documented the self‐reported prevalence of cannabinoid use in 457 patients with the diagnosis of FM and referred to a tertiary care pain center. We validated the diagnosis of FM and examined the associations of cannabinoid use in these patients.

Results

Cannabinoids were being used by 13% of all patients, of whom 80% used herbal cannabis (marijuana), 24% used prescription cannabinoids, and 3% used both herbal cannabis and prescription cannabinoids. One‐third of all men used cannabinoids. Current unstable mental illness (36% versus 23%; P = 0.002), opioid drug–seeking behavior (17% versus 4%; P = 0.002), and male sex (26% versus 7%; P = 0.0002) were all associated with herbal cannabis use. There was a trend for cannabinoid users to be unemployed and receiving disability payments. The diagnosis of FM was validated in 302 patients, with 155 assigned another primary diagnosis. When the FM group was analyzed separately, significant associations were lost, but trends remained.

Conclusion

Cannabinoids were used by 13% of patients referred with a diagnosis of FM. The association of herbal cannabis use with negative psychosocial parameters raises questions regarding the motive for this self‐medication practice. Although cannabinoids may offer some therapeutic effect, caution regarding any recommendation should be exercised pending clarification of general health and psychosocial problems, especially for those self‐medicating.
Taxonomy for systemic lupus erythematosus with onset before adulthood
Authors: Silva Clovis A. , Avcin Tadej , Brunner Hermine I.
Published: November 2012

Objective

To propose a common nomenclature to refer to individuals who fulfill the American College of Rheumatology classification criteria for systemic lupus erythematosus (SLE) during childhood or adolescence.

Methods

The medical literature was reviewed for studies conducted in the target population between 1960 and December 2011 to obtain information about the terms used to refer to such children and adolescents. We reviewed the threshold ages used and disease features considered to discriminate these individuals from patients with onset of SLE during adulthood. Furthermore, the nomenclature used in other chronic diseases with onset during both childhood and adulthood was assessed.

Results

There was an astonishing variability in the age cutoffs used to define SLE onset prior to adulthood, ranging from 14–21 years, but most studies used age 18 years. The principal synonyms in the medical literature were SLE without reference to the age at onset of disease, childhood‐onset SLE, juvenile SLE, and pediatric (or paediatric) SLE.

Conclusion

Based on the definition of childhood, in analogy with other complex chronic diseases commencing prior to adulthood, and given the current absence of definite genetic variations that discriminate adults from children, the term childhood‐onset SLE is proposed when referring to individuals with onset of SLE prior to age 18 years.
Obesity and reduction of the response rate to anti–tumor necrosis factor α in rheumatoid arthritis: An approach to a personalized medicine
Authors: Gremese Elisa , Carletto Antonio , Padovan Melissa , Atzeni Fabiola , Raffeiner Bernd , Giardina Anna Rita , Favalli Ennio Giulio , Erre Gian Luca , Gorla Roberto , Galeazzi Mauro , Foti Rosario , Cantini Fabrizio , Salvarani Carlo , Olivieri Ignazio , Lapadula Giovanni , Ferraccioli Gianfranco ,   for the Gruppo Italiano di Studio sulle Early Arthritis (GISEA)
Published: November 2012

Objective

Obesity is a mild, long‐lasting inflammatory disease and, as such, could increase the inflammatory burden of rheumatoid arthritis (RA). The study aim was to determine whether obesity represents a risk factor for a poor remission rate in RA patients requiring anti–tumor necrosis factor α (anti‐TNFα) therapy for progressive and active disease despite treatment with methotrexate or other disease‐modifying antirheumatic drugs.

Methods

Patients were identified from 15 outpatient clinics of university hospitals and hospitals in Italy taking part in the Gruppo Italiano di Studio sulle Early Arthritis network. Disease Activity Score in 28 joints (DAS28), body mass index (BMI; categorized as <25, 25–30, and >30 kg/m2), acute‐phase reactants, IgM rheumatoid factor, and anti–cyclic citrullinated peptide antibody values were collected. DAS28 remission was defined as a score of <2.6 lasting for at least 3 months.

Results

Six hundred forty‐one outpatients with longstanding RA receiving anti‐TNFα blockers (adalimumab, n = 260; etanercept, n = 227; infliximab, n = 154), recruited from 2006–2009 and monitored for at least 12 months, were analyzed. The mean ± SD DAS28 at baseline was 5.6 ± 1.4. A BMI of >30 kg/m2 was recorded in 66 (10.3%) of 641 RA patients. After 12 months of anti‐TNFα treatment, a DAS28 of <2.6 was noted in 15.2% of the obese subjects, in 30.4% of the patients with a BMI of 25–30 kg/m2, and in 32.9% of the patients with a BMI of <25 kg/m2 (P = 0.01). The lowest percentage of remission, which was statistically significant versus adalimumab and etanercept (P = 0.003), was observed with infliximab.

Conclusion

Obesity represents a risk factor for a poor remission rate in patients with longstanding RA treated with anti‐TNFα agents. A personalized treatment plan might be a possible solution.
Comparison of three methods for calculating the Bath Ankylosing Spondylitis Metrology Index in a randomized placebo‐controlled study
Authors: van der Heijde Désirée , Deodhar Atul , Inman Robert D. , Braun Jürgen , Hsu Ben , Mack Michael
Published: November 2012

Objective

To compare 3 methods for calculating the Bath Ankylosing Spondylitis Metrology Index (BASMI) score using patients who participated in the GO‐RAISE study.

Methods

Patients with active ankylosing spondylitis (AS) were randomly assigned in a 1:1.8:1.8 ratio to receive subcutaneous injections of placebo, golimumab 50 mg, or golimumab 100 mg every 4 weeks. Lumbar flexion, tragus‐to‐wall distance, lumbar side flexion, intermalleolar distance, and cervical rotation angle measurements at baseline, week 14, and week 24 were used to calculate the BASMI 2‐step (BASMI2), 10‐step (BASMI10), and linear (BASMIlin) scores.

Results

BASMI2 scores were generally lower than BASMI10 and BASMIlin scores, which were nearly identical. Median changes from baseline to week 14 in the combined golimumab group were similar to those in the placebo group when using the BASMI2 calculation method (0.00 versus 0.00; P = 0.288). The combined golimumab group showed significantly greater improvement from baseline to week 14 than the placebo group when using the BASMI10 (−0.20 versus 0.00; P = 0.018) and BASMIlin (−0.31 versus −0.07; P = 0.015) calculation methods, with the latter showing the greatest difference between golimumab and placebo. Guyatt's effect size was better for the BASMIlin and the BASMI10 versus the BASMI2 in the combined golimumab group at week 14 (0.58 and 0.53 versus 0.42, respectively) and week 24 (0.76 and 0.69 versus 0.61, respectively), despite the relatively short period to assess changes in spinal mobility.

Conclusion

The BASMIlin method was the most sensitive to changes in range of motion exhibited by patients with AS who received golimumab.
Dietary intake of vitamin D during adolescence and risk of adult‐onset systemic lupus erythematosus and rheumatoid arthritis
Authors: Hiraki Linda T. , Munger Kassandra L. , Costenbader Karen H. , Karlson Elizabeth W.
Published: November 2012

Objective

Vitamin D has immunomodulatory properties with potential etiologic implications for autoimmune diseases. The relevant exposure time during which vitamin D may influence disease risk is unknown. Our objective was to examine the relationship between reported vitamin D intake during adolescence and adult‐onset rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) incidence in prospective cohort studies of women, the Nurses' Health Study (NHS) and the Nurses' Health Study II (NHSII).

Methods

Food frequency questionnaires concerning high school diet completed by 73,629 NHS (1986) and 45,544 NHSII (1998) participants were used to calculate nutrient intakes during adolescence. Incident RA and SLE cases prior to 2006 (NHS) and 2007 (NHSII) were confirmed by medical record review. Cox proportional hazards models calculated relative risks and 95% confidence intervals of incident RA and SLE according to quintile cutoffs of vitamin D intake. Age‐ and calorie‐adjusted and multivariable‐adjusted (including sun exposure factors) analyses were completed. Random‐effects models were used to meta‐analyze estimates of association from the 2 cohorts.

Results

Incident RA was confirmed in 652 NHS and 148 NHSII participants and SLE was confirmed in 122 NHS and 54 NHSII participants over a mean followup time of 351 months (NHS) and 209 months (NHSII). Age‐ and calorie‐adjusted and multivariable‐adjusted models did not show significant associations between adolescent vitamin D intake and risk of adult‐onset RA or SLE.

Conclusion

We did not find associations between adolescent dietary vitamin D intake and adult RA or SLE risk among NHS and NHSII women, suggesting that other time periods during the life course should be studied.
Differences in physical activity patterns in patients with spondylarthritis
Authors: Haglund Emma , Bergman Stefan , Petersson Ingemar F. , Jacobsson Lennart T. H. , Strömbeck Britta , Bremander Ann
Published: November 2012

Objective

To study patient‐reported physical activity in patients with spondylarthritis (SpA) and possible differences in physical activity patterns between the SpA subtypes and sexes.

Methods

In 2009, a questionnaire including inquiries concerning physical activity was sent to patients with a SpA diagnosis (n = 3,711). The World Health Organization (WHO) global recommendations of physical activity for health requiring 150 minutes of moderate‐intensity physical activity (MI‐PA) or 75 minutes of vigorous‐intensity physical activity (VI‐PA) per week were used as recommended levels. Standardized risk ratios (RRs) were calculated by using physical activity data from the Swedish population. The association within the SpA group between sex, age, disease‐related variables, anxiety, and depression and meeting recommended levels of MI‐PA and VI‐PA (dependent variables) was studied with multivariate analysis.

Results

A total of 2,167 patients with SpA (48% men, mean ± SD age 55 ± 14 years) responded to the questionnaire. Sixty‐eight percent of the patients met the WHO recommendations, more frequently in women than in men (70% versus 66%). The recommendations were more often met in the SpA group (RR 1.09, 95% confidence interval [95% CI] 1.04–1.15) compared with the Swedish population. There was a tendency for young women to meet the WHO recommendations less often than the Swedish population (RR 0.94, 95% CI 0.63–1.25). Different factors were found to influence whether the patients were exercising with a moderate or vigorous intensity.

Conclusion

Seven of 10 patients with SpA met the WHO recommendations of physical activity for health, but we found sex and disease subtype differences. This information can be useful in clinical practice when coaching patients to have a healthier lifestyle.
Foot‐related health care use in patients with rheumatoid arthritis in an outpatient secondary care center for rheumatology and rehabilitation in The Netherlands: A cohort study with a maximum of fifteen years of followup
Authors: Marsman Anneke F. , Dahmen Rutger , Roorda Leo D. , van Schaardenburg Dirkjan , Dekker Joost , Britsemmer Karin , Knol Dirk L. , van der Leeden Marike
Published: November 2012

Objective

To describe foot‐related health care use over time in a cohort of rheumatoid arthritis (RA) patients in an outpatient secondary care center for rheumatology and rehabilitation in The Netherlands.

Methods

A total of 1,087 patients with recent‐onset RA from 1995 to September 2010 were included in the study. All foot‐related visits to the podiatrist, rehabilitation physician, orthopedic surgeon, and the multidisciplinary foot‐care clinic were registered and described. Logistic regression techniques for longitudinal data were used to analyze the course of foot‐related health care use.

Results

A total of 32.9% of patients visited a podiatrist in secondary care during the course of their disease. For most patients, a visit to the podiatrist took place during the first year after diagnosis. This was followed by a significant decrease in visits in the ensuing years. Nine percent of patients visited the rehabilitation physician with foot symptoms, with peak prevalences between year 10 and 11 and during year 14 of followup. The orthopedic surgeon was visited by 5.3% of patients with foot symptoms, with a significant increase in visits over time. The multidisciplinary foot‐care clinic was visited by 7.5% of patients. This was significantly associated with visits to the rehabilitation physician.

Conclusion

In an outpatient secondary care center in The Netherlands, RA patients with foot symptoms visited the podiatrist in an early stage of the disease. When foot symptoms worsened, patients visited the rehabilitation physician, who subsequently referred patients to the multidisciplinary foot‐care clinic for therapeutic footwear. The orthopedic surgeon was the final step in the management of foot symptoms.
Patient self‐report RADAI (Rheumatoid Arthritis Disease Activity Index) joint counts on an MDHAQ (Multidimensional Health Assessment Questionnaire) in usual care of consecutive patients with rheumatic diseases other than rheumatoid arthritis
Authors: Castrejón Isabel , Yazici Yusuf , Pincus Theodore
Published: November 2012

Objective

To analyze a patient self‐report joint count from the Rheumatoid Arthritis Disease Activity Index (RADAI) on a Multidimensional Health Assessment Questionnaire (MDHAQ) in a cohort of consecutive patients seen in usual rheumatology care with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), osteoarthritis (OA), psoriatic arthritis (PsA), and gout.

Methods

Each patient completed an MDHAQ, which included a RADAI, at each visit in one usual care setting. In order to include a physician measure, a random visit at which there was a recorded physician global estimate was selected for each of 465 patients (174 patients with RA, 75 with SLE, 113 with OA, 53 with PsA, and 50 patients with gout). The RADAI was analyzed for total scores (range 0–48), number of involved joint groups (range 0–16), and each specific joint group, and then compared in the 5 diagnostic groups to one another and to other MDHAQ measures and the Routine Assessment of Patient Index Data 3 (RAPID3).

Results

In patients with RA, SLE, OA, PsA, and gout, mean RADAI scores (range 0–48) were 12.4, 6.5, 10.1, 6.7, and 2.7, respectively. The mean numbers of involved joint groups (range 0–16) were 6.9, 3.8, 4.8, 4.5, and 1.7, respectively, and the median numbers were 6, 2, 4, 4, and 1, respectively. RADAI scores were correlated significantly with the physician global estimate, except in SLE, and at higher levels with the MDHAQ and RAPID3 scores in all diagnostic groups.

Conclusion

The RADAI self‐report joint counts can be used to record self‐report involvement of specific joints and joint groups in patients with SLE, OA, PsA, and gout, with minimal effort on the part of the rheumatologist.