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Aim: This Study Aimed to Assess the Intention to Have a Third Child among Millennial Parents (25–40 years old) with Two Children in a City in Eastern China and to Explore the Influencing Factors Related to Fertility Intention. Design: A cross‐sectional design study. Methods: A convenience sampling method was used to enrol participants of childbearing age who visited two tertiary hospitals in Hang zhou, a city in eastern China, from June 2021 to March 2022. We conducted a face‐to‐face questionnaire survey with 520 participants and calculated the prevalence of intention‐related factors. Multivariate logistic regression was used to analyse the independent influencing factors of fertility intention. Results: In total, 105 (20.2%) participants had the intention to have a third child. The results showed that 'employment status', 'age', 'reasons for wanting a third child', the considered 'biggest barrier to having a third child', 'views on the three‐child policy', 'desired free services', 'supporting work policies' and 'assistance policies' were significant independent influencing factors of intention to have a third child (p‐value < 0.05). The intention of the participants 'over 30 years old' was 2.466 times that of those '30 years old and under', and 'older age/personal health status' was considered the 'biggest barrier to having a third child'. Regarding policy and social reasons, the participants who need 'medical assistance' policy negatively affect the intention to have a third child (OR = 0.453, 95% CI = 0.247–0.830). Implications for Healthcare/Nursing: Nursing plays an important role in health promotion. Nurses can help couples make wise decisions about fertility by providing professional consultation, education, evaluation and support. They can also provide corresponding nursing and guidance to improve couples' health quality and overall reproductive success. Conclusions: The general level of intention to have a third child of Millennial parents with two children is still low. The participants who are 'housewives/househusbands', 'over 30 years old', and satisfied with the state of 'medical assistance' have higher fertility intentions. Patient or Public Contribution: It is particularly meaningful for the policymakers to improve the social support system and raise universal awareness to encourage childbirth. [ABSTRACT FROM AUTHOR]

Aim: To translate and culturally adapt the FRAIL scale into Spanish and perform a preliminary test of diagnostic accuracy in patients admitted to intensive care units. Design: Cross‐sectional diagnostic study. Methods: Five intensive care units (ICU) in Spain were participated. Stage 1: Three native Spanish‐speaking bilingual translators familiar with the field of critical care translated the scale from English into Spanish. Stage 2: Three native English‐speaking bilingual translators familiar with critical care medicine. Stage 3: Authors of the original scale compared the English original and back‐translated versions of the scale. Stage 4: Five nurses with more than 5 years of ICU experience and five critical care physicians assessed the comprehension and relevance of each of the items of the Spanish version in 30 patients of 3 different age ranges (<50, 50–65 and >65 years). Results: The FRAIL scale was translated and adapted cross‐culturally for patients admitted to intensive care units in Spain. The process consisted of four stages: translation, back translation, comparison and pilot test. There was good correspondence between the original scale and the Spanish version in 100% of the items. The participating patients assessed the relevance (content validity) and comprehensibility (face validity) of each of the items of the first Spanish version. The relevance of some of the items scored low when the scale was used in patients younger than 65 years. Conclusions: We have cross‐culturally adapted the FRAIL scale, originally in English, to Spanish for its use in the critical care medical setting in Spanish‐speaking countries. Implications for Professionals: Physicians and nurses can apply the new scale to all patients admitted to the intensive care units. Nursing care can be adapted according to frailty, trying to reduce the side effects of admission to these units for the most fragile patients. Reporting Method: The manuscript's authors have adhered to the EQUATOR guidelines, using the COSMIN reporting guideline for studies on the measurement properties of patient‐reported outcome measures. Patient or Public Contribution: In a pilot clinical study, we applied the first version of the FRAIL‐Spain scale to intensive care unit (ICU) patients. Five nurses with more than 5 years of ICU experience and five critical care physicians assessed the relevance (content validity) and comprehensibility (face validity) of the five items of the first Spanish version. Relevance was assessed using a 4‐point Likert scale ranging from 1 (no relevance) to 4 (high relevance), and comprehensibility was assessed as poor, acceptable or good. Each health professional applied the scale to three patients (total number of patients = 30) of three different age ranges (<50, 50–65 and >65 years) and recorded the time of application of the scale to each patient. Although the frailty scales were initially created by geriatricians to be applied to the elders, there is little experience with their application in critically ill patients of any age. Therefore, more information is needed to determine the relevance of using this scale in critical care patients. In this pilot study, we considered that nurses and critical care physicians should evaluate frailty using this adapted scale in adult patients admitted to the Intensive Care Units. [ABSTRACT FROM AUTHOR]

Background: Reported risk of bleeding complications after central catheter access in patients with thrombocytopenia is highly variable. Current guidelines recommend routine prophylactic platelet (PLT) transfusion before central venous catheter placement in patients with severe thrombocytopenia. Nevertheless, the strength of such recommendations is weak and supported by observational studies including few patients with very low PLT counts (<20 × 109/L). This study aims to assess the risk of bleeding complications related to using or not using prophylactic PLT transfusion before ultrasound‐guided central venous access in patients with very low PLT counts. Methods: This was a retrospective cohort study of patients with very low PLT counts (<20 × 109/L) subjected to ultrasound‐guided central venous catheterization between January 2011 and November 2019 in a university hospital. Bleeding complications were graded according to the Common Terminology Criteria for Adverse Events. A multivariate logistic regression was conducted to assess the risk of major and minor bleeding complications comparing patients who did or did not receive prophylactic PLT transfusion for the procedure. Multiple imputation by chained equations was used to handle missing data. A two‐tailed p < 0.05 was considered statistically significant. Results: Among 221 patients with very low PLT counts, 72 received prophylactic PLT transfusions while 149 did not. Baseline characteristics were similar between transfused and nontransfused patients. No major bleeding events were identified, while minor bleeding events were recognized in 35.7% of patients. Multivariate logistic regression analysis showed no significant differences in bleeding complications between patients who received prophylactic PLT transfusions and those who did not (odds ratio 0.83, 95% confidence interval 0.45–1.55, p = 0.567). Additional complete case and sensitivity analyses yielded results similar to those of the main analysis. Conclusions: In this single‐center retrospective cohort study of ultrasound‐guided central venous access in patients with very low PLT counts, no major bleeding was identified, and prophylactic PLT transfusions did not significantly decrease minor bleeding events. [ABSTRACT FROM AUTHOR]

Improving the dietary quality of women and children is essential to reduce all forms of malnutrition. In this study, we assessed seasonal child and maternal dietary diversity and consumption of animal‐source foods (ASF), using 1,236 observations from combined data collected among 167 mother–child dyads in rural Timor‐Leste. We used generalized linear and logistic mixed‐effects models to examine the dietary differentials of mothers and children in two agricultural livelihood zones and across the seasons, as well as to identify household and agroecological characteristics associated with children's dietary quality in relation to their mothers'. We found dietary quality to be marginally better in coastal than in mid‐altitude zones. However, women's diets were strikingly poor, and their intake of ASF was lower than among children. Mothers exhibited preferential allocation patterns of specific ASF, dairy products and eggs, to children. The intake of ASF was predicted by seasonality. Flesh foods and red meat were much more likely to be consumed during the dry season, when cultural ceremonies are often performed. We found a positive and strongly significant association between children's dietary indicators—dietary diversity score, minimum dietary diversity and ASF consumption, and those of their mothers'. Maternal dietary quality and educational attainment, more so than agroecological characteristics, were explanatory factors of children's diet. Our study highlights that addressing the dietary quality of children in Timor‐Leste would benefit from improving women's diets through better access to nutritious foods and to secondary education. [ABSTRACT FROM AUTHOR]

To assess the vitamin D status in healthy 6‐month‐old infants, as well as vitamin D supplementation and feeding patterns in Guangzhou, China, serum 25‐hydroxyvitamin D (25OHD) concentrations of 202 infants were measured at birth (cord blood) and at 6 months of age in Guangzhou, China. Questionnaires acquiring demographic characteristics, maternal and infantile vitamin D supplementation during pregnancy and first 6 months after birth, and feeding patterns during the first 6 months were completed by participating mothers. Physical examinations and blood sampling were carried out among infants at 6 months of age. The majority of infants (93.6%) were supplemented with vitamin D during the first 6 months of life on a voluntary basis. The M ± SD of cord serum 25OHD concentration was 46.2 ± 16.4 nmol/L, whereas the M ± SD of 25OHD concentration at 6 months was 82.9 ± 24.9 nmol/L. Serum 25OHD concentrations <30 nmol/L were seen in 34 (16.8%) infants at birth but only one (0.5%) at 6 months. Only 11 (5.4%) infants had concentrations >75 nmol/L at birth, whereas the majority of infants (n = 131, 64.9%) had concentrations >75 nmol/L at 6 months. The main predictors of 25OHD levels at 6 months included season, vitamin D supplementation, parental education level, and feeding patterns. To conclude, serum 25OHD concentrations were low at birth in a southern Chinese population, and infantile supplementation is an effective way to improve 25OHD status. Exclusively breastfed infants might need greater vitamin D supplementation, and individualized vitamin D supplementation plans might be needed. [ABSTRACT FROM AUTHOR]

Background: As citizens, patients and family members are participating in numerous and expanding roles in health system organizations, attention has turned to evaluating these efforts. The context‐specific nature of engagement requires evaluation tools to be carefully designed for optimal use. We sought to address this need by assessing the appropriateness and feasibility of a generic tool across a range of health system organizations, engagement activities and patient groups. Methods: We used a mixed‐methods implementation research design to study the implementation of an engagement evaluation tool in seven health system organizations in Ontario, Canada focusing on two key implementation outcome variables: appropriateness and feasibility. Data were collected through respondent feedback questions (binary and open‐ended) at the end of the tool's three questionnaires as well as interviews and debriefing discussions with engagement professionals and patient partners from collaborating organizations. Results: The three questionnaires comprising the evaluation tool were collectively administered 29 times to 405 respondents yielding a 52% response rate (90% and 53% of respondents respectively assessed the survey's appropriateness and feasibility [quantitatively or qualitatively]). The questionnaires' basic properties were rated highly by all respondents. Concrete suggestions were provided for improving the appropriateness and feasibility of the questionnaires (or components within) for different engagement activity and organization types, and for enhancing the timing of implementation. Discussion and Conclusions: Our study findings offer guidance for health system organizations and evaluators to support the optimal use of engagement evaluation tools across a variety of health system settings, engagement activities and respondent groups. [ABSTRACT FROM AUTHOR]

Abstract: Maternal undernutrition and mortality remain high in several African countries. Key nutrition and health interventions improve maternal and birth outcomes. Evidence is scarce on how to strengthen health systems to ensure pregnant women and newborns are reached with these interventions. We conducted three quasi‐experimental nonrandomized Community Based Maternal and Neonatal Health and Nutrition projects in regions of Ethiopia, Senegal, and Kenya to demonstrate how proven nutrition interventions could be integrated into health programs to improve knowledge and practices during pregnancy, birth, and postpartum. We evaluated impact on knowledge and practices related to maternal and neonatal care using logistic regression and repeated‐measures models with districts as a fixed variable and adjusted for covariates. Combined country analyses show significant positive effects of the intervention on women receiving first antenatal care visit (ANC) during first trimester (OR = 1.44; p < .001), those consuming any iron and folic acid supplement during their latest pregnancy (OR = 1.60; p = .005), those whose <6 months infants were exclusively breastfed (OR = 2.01; p=.003), those whose delivery was facility based (OR = 1.48; p=.031), and those whose postnatal care was facility based (OR = 2.15; p<.001). There was no significant differences between intervention and control groups regarding one or more and four or more ANC visits, women consuming iron and folic acid for ≥90 days, and early initiation of breastfeeding. We conclude that integrating proven nutrition interventions into health programs at community level improved components of access to and use of ANC, delivery services, and postnatal care by women in three African countries. [ABSTRACT FROM AUTHOR]

Maternal capabilities-qualities of mothers that enable them to leverage skills and resources into child health-hold potential influence over mother's adoption of child caring practices, including infant and young child feeding. We developed a survey ( n = 195) that assessed the associations of 4 dimensions of maternal capabilities (social support, psychological health, decision making, and empowerment) with mothers' infant and young child feeding practices and children's nutritional status in Uganda. Maternal responses were converted to categorical subscales and an overall index. Scale reliability coefficients were moderate to strong (α range = 0.49 to 0.80). Mothers with higher social support scores were more likely to feed children according to the minimum meal frequency (odds ratio [OR] [95% confidence interval (CI)] = 1.38 [1.10, 1.73]), dietary diversity (OR [95% CI] = 1.56 [1.15, 2.11]), iron rich foods, (OR [95% CI] = 1.47 [1.14, 1.89]), and minimally acceptable diet (OR [95% CI] = 1.55 [1.10, 2.21]) indicators. Empowerment was associated with a greater likelihood of feeding a minimally diverse and acceptable diet. The maternal capabilities index was significantly associated with feeding the minimum number of times per day (OR [95% CI] = 1.29 [1.03, 1.63]), dietary diversity (OR [95% CI] = 1.44 [1.06, 1.94]), and minimally acceptable diet (OR [95% CI] = 1.43 [1.01, 2.01]). Mothers with higher psychological satisfaction were more likely to have a stunted child (OR [95% CI] = 1.31 [1.06, 1.63]). No other associations between the capabilities scales and child growth were significant. Strengthening social support for mothers and expanding overall maternal capabilities hold potential for addressing important underlying determinants of child feeding in the Ugandan context. [ABSTRACT FROM AUTHOR]

Premastication of infant food by caregivers is common in Laos. Premastication is hypothesized to have both positive and negative implications for children, but the net effect of premastication on child health and nutrition is largely unknown because of a lack of research. This study quantitatively describes premastication in 5 provinces of Laos and examines the associations between premastication and the length of young children. We analyzed cross-sectional data from the Laos 2015 Food and Nutrition Security Survey to characterize premastication among children under 2 years of age ( n = 1,661) and to test associations between premastication and child length-for-age z-score. We explored associations using multilevel mixed effects linear regression. Among children 0-23 months, 27.2% of mothers reported giving premasticated food in the past week. Receipt of premasticated food was inversely associated with length-for-age z-score after controlling for potential confounders (child's age, ethno-linguistic group, wealth, and parity) among children 6-13 months (β −0.36, CI [−0.68, −0.04]) and among children 14-23 months (β −0.43, CI [−0.81, −0.05]). For breastfed children 0-5 months who received complementary food, the coefficient was similar, but the association was not statistically significant (β −0.42, CI [−1.2, 0.37]). Premastication is a common feeding practice for children 0-23 months of age, and many infants consume premasticated food on a daily basis. There was a negative relationship between premastication and child length. However, given the cross-sectional nature of this study and potential unmeasured confounding factors, reverse causality or confounding cannot be ruled out. Longitudinal studies are needed to develop recommendations on premastication. [ABSTRACT FROM AUTHOR]

Vitamin B6 is important in fetal development, but little is known of the vitamin B6 status of pregnant women and newborns in North America and potential modifying factors. This prospective study determined maternal and cord plasma concentrations of pyridoxal 5′ phosphate (PLP; an indicator of vitamin B6 status) in a convenience sample of 368 Canadian pregnant women and their newborns. The association of maternal intake of vitamin B6 and fetal genetic variants with cord plasma PLP and homocysteine concentrations was also examined. Dietary and supplemental intakes of vitamin B6 were assessed in early and mid to late pregnancy. PLP concentrations were measured in maternal plasma in early pregnancy and at delivery, and in cord plasma. Six fetal variants of the MTHFR and CβS genes were assessed for their association with cord plasma PLP and homocysteine concentrations. Geometric mean (95% CI) PLP concentrations were 107 (98, 116) nmol/L in early pregnancy and 58 (53, 62) nmol/L at delivery, respectively, and 296 (275, 319) nmol/L in cord blood ( p < .0001). During early pregnancy and at delivery, 3.6% and 5.5% of women had plasma PLP concentrations <20 nmol/L, respectively. Ninety eight percent of the women with supplemental B6 intake of at least the recommended dietary allowance had PLP concentrations >20 nmol/L. Fetal genetic variants were not associated with cord PLP and homocysteine concentrations. Vitamin B6 deficiency is uncommon in a cohort of Canadian pregnant women due largely to prevalent vitamin B6 supplement use. [ABSTRACT FROM AUTHOR]

Gestational vitamin D insufficiency is related with increased risks of various diseases and poor health outcomes later in life. Telomere length at birth or early in life is known to be a predictor of individual health. Both vitamin D and telomere length are related with various health conditions, and vitamin D concentrations are associated with leukocyte telomere lengths in women. We investigated the association between maternal vitamin D concentrations and newborn leukocyte telomere lengths. This cross-sectional study included 106 healthy pregnant women without adverse obstetric outcomes and their offspring. We examined the maternal age, weight before pregnancy, health behaviours, and nutritional intakes, along with each newborn's sex and birthweight, and we measured maternal height, telomere length, total white blood cell count, and glycosylated haemoglobin as covariates. Pearson's correlation coefficients were calculated to evaluate the relationship between the baseline variables and newborn leukocyte telomere lengths. To confirm that there was an independent association between newborn leukocyte telomere lengths and maternal vitamin D concentrations, we performed a stepwise multiple linear regression analysis. Newborn leukocyte telomere lengths correlated positively with maternal leukocyte telomere lengths ( r = .76, p < .01), maternal 25-hydroxyvitamin D concentrations ( r = .72, p < .01), maternal energy intakes ( r = .22, p = .03), and newborn body weights ( r = .51, p < .01). In the multivariate model, newborn leukocyte telomere lengths were associated with maternal vitamin D concentrations (β = .33, p < .01). These findings suggest that the maternal vitamin D concentration during pregnancy may be a significant determinant of the offspring's telomere length. [ABSTRACT FROM AUTHOR]

Home fortification of complementary foods (CFs) with multiple micronutrient powders (MNPs) is being scaled up in various countries, but little is known about the prevailing complementary feeding practices and the type and nutrient gaps to be filled with MNPs. The present study evaluated the complementary feeding practices of young children and simulated the risk of inadequate and excessive intakes associated with home fortification with MNPs. We have assessed the sociodemographic status, anthropometry, and complementary feeding practices of young children ( N = 122) in Mecha district, rural Ethiopia. Using a 2-day, quantitative 24-hr recall, usual intakes of energy, protein, iron, zinc, and calcium were estimated. The risks of inadequate and excessive iron and zinc intakes with or without home fortification scenarios were assessed. The simulations considered intakes from CFs assuming average breast milk contributions and additional nutrients provided by the MNPs. Stunting was highly prevalent (50%) and was associated with a lower dietary diversity ( P = .009) and nutrient intakes from the CFs. Median energy, zinc, and calcium intakes were below the estimated needs from CFs; protein needs were met. Median dietary iron intake appeared adequate, but 76%, 95% CI [68%, 84%], of children had inadequate intake (assuming low bioavailability), whereas another 8%, 95% CI: [3%, 13%], had excessive intakes. Simulation of daily and alternative day's fortification with MNP decreased the prevalence of inadequate iron and zinc intake but significantly increased the risk of excessive intakes that remained unacceptably high for iron (>2.5%). Untargeted MNP interventions may lead to excessive intakes, even in settings where poor complementary feeding practices are prevalent. [ABSTRACT FROM AUTHOR]

Premixed flours for infant porridge are increasingly produced and sold in developing countries to complement continued breastfeeding. Such complementary food (CF) products have known efficacy against malnutrition in children from 6 to 24 months of age, but ingredient ratios and production processes may vary. This study provides the first systematic measurement of their actual nutrient composition. We purchased samples of 108 premixed CF products in 22 low- and middle-income countries, and commissioned blind laboratory measurement of each product's macronutrients and micronutrients. We compared measured contents to nutrient claims on their packaging and to CF standards from the Codex Alimentarius, the Super Cereal Plus product used in nutrition assistance programs, and the Lutter and Dewey (2003) recommendations, as well as our own modeled nutrient requirements for a healthy breastfed child. Actual densities are significantly different from nutrient claims for protein ( p = .013) and fat ( p = .000). Only 15% of samples met two of the three benchmarks for fat, 32% met the most stringent protein standard, while only 22% met them for iron, and 21% for zinc. The median healthy child consuming breast milk plus enough of these solid foods to meet energy needs would experience deficits of zinc at 6 months, iron at 6 and 9 months, and dietary fat from 12 months of age. In summary, premixed CF products can provide adequate nutrient density but usually do not, revealing the need and opportunity for independent monitoring and quality assurance to help grain millers making premixed foods maintain uniform ingredient ratios and production practices. [ABSTRACT FROM AUTHOR]

Objective Transcription factor p63, of the p53 family, regulates cell proliferation, survival, and apoptosis in various cells and tissues. This study was undertaken to examine the expression and roles of p63 transcript variants in the mouse growth plate and articular chondrocytes. Methods For in vivo analyses, we generated Cre-mediated TAp63α-transgenic and TAp63γ-transgenic mice. To induce tissue-specific overexpression or deletion in chondrocytes, chondroprogenitor cells, or early limb bud mesenchymal cells, we used Col2a1-Cre, Sox9-Cre, and Prx1-Cre mice, respectively. We analyzed osteoarthritis (OA) development with aging or surgically induced instability in Prx1-Cre;p63fl/fl (P-conditional knockout) mice. Results Among major variants, TAp63α and TAp63γ are highly expressed in mouse primary costal and articular chondrocytes. The p63 protein was predominantly localized in the hypertrophic zone of the embryonic limb cartilage, and in the middle zone of articular cartilage. No obvious change was observed in skeletal growth of TAp63α-transgenic mice, Sox9-Cre;p63fl/fl, or P-conditional knockout mice, while that of TAp63γ-transgenic mice was impaired due to ectopic apoptosis and the resulting decreased number of chondrocytes. Expression of proapoptotic genes including bax, noxa, puma, and fas was increased in TAp63γ-transgenic mouse chondrocytes, and their transcription was probably sustained by p53 in p63-conditional knockout mouse chondrocytes because both proteins were coexpressed in the growth plate. In contrast, p53 was expressed in the superficial zone of articular cartilage, differently from p63. Notably, P-conditional knockout mice showed significant resistance to OA development, with suppression of chondrocyte apoptosis in the aging and surgical models. Conclusion We demonstrated regulation of chondrocyte survival in articular cartilage by p63. [ABSTRACT FROM AUTHOR]

Objective The American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR) have defined remission using Boolean- or index-based criteria (i.e., a Simplified Disease Activity Index [SDAI] score of ≤3.3). We undertook this study to compare definitions of remission to inform choice of end points for future rheumatoid arthritis (RA) clinical trials, and we also included in our comparison the remission criterion of a score of ≤2.8 on the Clinical Disease Activity Index (CDAI). Methods We performed post hoc analyses on clinical remission rates using data from 2 infliximab trials (the ASPIRE [Active-Controlled Study of Patients Receiving Infliximab for the Treatment of Rheumatoid Arthritis of Early Onset] and ATTRACT [Anti-Tumor Necrosis Factor Trial in Rheumatoid Arthritis with Concomitant Therapy] trials) and 1 golimumab trial (the GO-FORWARD trial). We investigated stringency of the different remission definitions, their power to discriminate between active drug and comparator, and aspects of their internal and external validity. We also investigated population determinants of discriminatory power for a particular remission end point. Results In patients with early RA (the ASPIRE trial), ACR/EULAR Boolean, CDAI, and SDAI remission rates at 6-7 months were 4-6% for methotrexate (MTX) alone versus 11-14% for infliximab plus MTX. In patients with MTX-refractory active RA (the ATTRACT and GO-FORWARD trials), remission rates were ≤1% for comparator (add-on of placebo) versus 4-6% for add-on of infliximab in the ATTRACT trial and ≤3% for comparator (add-on of placebo) versus 11-13% for add-on of golimumab in the GO-FORWARD trial. Existing remission cut points of different measures were generally comparable, with the Boolean criteria being somewhat more stringent than the SDAI and CDAI criteria. Remission rates were similar across definitions, as was average statistical power (CDAI, 55.6%; Boolean, 59.9%; SDAI, 62.6%). Conclusion Remission is an ambitious primary end point for RA clinical trials, to be reserved for selected scenarios based on power considerations. The ACR/EULAR definitions are interchangeable, with slightly higher stringency of Boolean criteria over index-based criteria. [ABSTRACT FROM AUTHOR]

Objective Coronary artery disease (CAD) in the general population is characterized by an increased frequency of particular susceptibility single-nucleotide polymorphisms (SNPs). Because the frequency of CAD is increased among patients with rheumatoid arthritis (RA), we sought to determine whether the frequency of these SNPs is increased in RA patients with CAD, hypothesizing that RA could enhance CAD risk by acting through established genetic pathways predisposing to CAD. Methods Coronary artery calcification (CAC) as detected by computed tomography was used as a measure of CAD in 561 patients with RA. One hundred SNPs associated with CAD in the general population were genotyped or imputed, and their relationship to CAC was established through multiple regression analysis for individual SNPs and a genetic risk score representing their cumulative effect. Results Ninety-one CAD-related SNPs were genotyped successfully; of these, 81 exhibited no association with CAC (Agatston units) or different CAC categorizations, either individually or collectively, in the genetic risk score. Only rs579459 ( ABO) and rs17676451 ( HAL) had a consistent positive association between genotype and CAC, with a significant increase in the frequency of the effect allele in both homozygous and heterozygous genotype distributions. Five were variably negatively associated. Furthermore, a positive association between the Disease Activity Score in 28 joints and CAC was observed, and after adjustment for traditional cardiovascular risk factors, it was not modified by correcting for the CAD-related SNP genetic risk score. Conclusion The increased risk of CAC in patients with RA does not appear to operate primarily through established genetically regulated atherogenic mechanisms that are preponderant in the general population. [ABSTRACT FROM AUTHOR]

Objective Cytosolic DNA sensors detect microbial DNA and promote type I interferon (IFN) and proinflammatory cytokine production through the adaptor stimulator of IFN genes (STING) to resolve infection. Endogenous DNA also engages the STING pathway, contributing to autoimmune disease. This study sought to identify the role of STING in regulating bone formation and to define the bone phenotype and its pathophysiologic mechanisms in arthritic mice double deficient in DNase II and IFN-α/β/ω receptor (IFNAR) (DNase II−/−/IFNAR−/− double-knockout [DKO] mice) compared with controls. Methods Bone parameters were evaluated by micro-computed tomography and histomorphometry in DKO mice in comparison with mice triple deficient in STING, DNase II, and IFNAR and control mice. Cell culture techniques were employed to determine the parameters of osteoclast and osteoblast differentiation and function. NanoString and Affymetrix array analyses were performed to identify factors promoting ectopic bone formation. Results Despite the expression of proinflammatory cytokines that would be expected to induce bone loss in the skeleton of DKO mice, the results, paradoxically, demonstrated an accumulation of bone in the long bones and spleens, sites of erythropoiesis and robust DNA accrual. In addition, factors promoting osteoblast recruitment and function were induced. Deficiency of STING significantly inhibited bone accrual. Conclusion These data reveal a novel role for cytosolic DNA sensor pathways in bone in the setting of autoimmune disease. The results demonstrate the requirement of an intact STING pathway for bone formation in this model, a finding that may have relevance to autoimmune diseases in which DNA plays a pathogenic role. Identification of pathways linking innate immunity and bone could reveal novel targets for the treatment of bone abnormalities in human autoimmune diseases. [ABSTRACT FROM AUTHOR]

Objective Human endogenous retroviruses (HERVs) are remnants of past retroviral infections in the human genome and have been implicated in different aspects of human biology. The aim of this study was to identify HERVs that are associated with the pathogenesis of rheumatic diseases such as systemic lupus erythematosus (SLE). Methods The study subjects included 45 female patients with SLE and 50 healthy controls matched for geographic area, age, and sex. Real-time reverse transcription-polymerase chain reaction analysis was used to examine the transcription levels of 11 genes with coding capacity for complete envelope (Env) protein in these individuals. In this way, 1 HERV locus was identified as a potential modulator of autoimmunity. The env gene encoded by this HERV locus was cloned and examined for the ability to express a functional protein with immunosuppressive potential. Results Expression of the env59 gene was negatively correlated with pathogenetic factors of human autoimmune rheumatic diseases, including such factors as the levels of interleukin-6 (IL-6) and Toll-like receptor 7. This gene was capable of encoding a fully functional Env glycoprotein that was found to contain a domain, the immunosuppressive (ISU) domain, that, when evaluated ex vivo in patients with SLE and those with rheumatoid arthritis as well as in animal models, showed strong antiinflammatory activity, including the ability to lower IL-6 levels. Conclusion The env59 gene has been adapted by the immune system as a control mechanism in autoimmunity. The peptides derived from the ISU domain contained in the Env59 protein may be useful as potentially new biologic treatments in rheumatic diseases such as SLE. [ABSTRACT FROM AUTHOR]

Objective To assess the efficacy and safety of anifrolumab, a type I interferon (IFN) receptor antagonist, in a phase IIb, randomized, double-blind, placebo-controlled study of adults with moderate-to-severe systemic lupus erythematosus (SLE). Methods Patients (n = 305) were randomized to receive intravenous anifrolumab (300 mg or 1,000 mg) or placebo, in addition to standard therapy, every 4 weeks for 48 weeks. Randomization was stratified by SLE Disease Activity Index 2000 score (<10 or ≥10), oral corticosteroid dosage (<10 or ≥10 mg/day), and type I IFN gene signature test status (high or low) based on a 4-gene expression assay. The primary end point was the percentage of patients achieving an SLE Responder Index (SRI[4]) response at week 24 with sustained reduction of oral corticosteroids (<10 mg/day and less than or equal to the dose at week 1 from week 12 through 24). Other end points (including SRI[4], British Isles Lupus Assessment Group [BILAG]-based Composite Lupus Assessment [BICLA], modified SRI[6], and major clinical response) were assessed at week 52. The primary end point was analyzed in the modified intent-to-treat (ITT) population and type I IFN-high subpopulation. The study result was considered positive if the primary end point was met in either of the 2 study populations. The Type I error rate was controlled at 0.10 (2-sided), within each of the 2 study populations for the primary end point analysis. Results The primary end point was met by more patients treated with anifrolumab (34.3% of 99 for 300 mg and 28.8% of 104 for 1,000 mg) than placebo (17.6% of 102) ( P = 0.014 for 300 mg and P = 0.063 for 1,000 mg, versus placebo), with greater effect size in patients with a high IFN signature at baseline (13.2% in placebo-treated patients versus 36.0% [ P = 0.004] and 28.2% [ P = 0.029]) in patients treated with anifrolumab 300 mg and 1,000 mg, respectively. At week 52, patients treated with anifrolumab achieved greater responses in SRI(4) (40.2% versus 62.6% [ P < 0.001] and 53.8% [ P = 0.043] with placebo, anifrolumab 300 mg, and anifrolumab 1,000 mg, respectively), BICLA (25.7% versus 53.5% [ P < 0.001] and 41.2% [ P = 0.018], respectively), modified SRI(6) (28.4% versus 49.5% [ P = 0.002] and 44.7% [ P = 0.015], respectively), major clinical response (BILAG 2004 C or better in all organ domains from week 24 through week 52) (6.9% versus 19.2% [ P = 0.012] and 17.3% [ P = 0.025], respectively), and several other global and organ-specific end points. Herpes zoster was more frequent in the anifrolumab-treated patients (2.0% with placebo treatment versus 5.1% and 9.5% with anifrolumab 300 mg and 1,000 mg, respectively), as were cases reported as influenza (2.0% versus 6.1% and 7.6%, respectively), in the anifrolumab treatment groups. Incidence of serious adverse events was similar between groups (18.8% versus 16.2% and 17.1%, respectively). Conclusion Anifrolumab substantially reduced disease activity compared with placebo across multiple clinical end points in the patients with moderate-to-severe SLE. [ABSTRACT FROM AUTHOR]

Objective Systemic lupus erythematosus (SLE) is a debilitating autoimmune disease affecting multiple organs in the body, but therapeutic options are still very limited and often come with adverse effects. Increasing evidence has underlined an important role of the Toll-like receptor 7 (TLR-7)/TLR-9/interleukin-1 receptor-associated kinase 1 (IRAK-1)/interferon regulatory factor 7 (IRF-7) pathway in the development and progression of SLE. Notably, the prolyl isomerase Pin1 is an essential regulator of IRAK-1 in TLR-7/TLR-9 signaling, but its role in SLE is unknown. We undertook this study to determine whether Pin1 is activated and plays any role in the development and treatment of SLE. Methods Activation of Pin1 and TLR-7/TLR-9/IRAK-1/IRF-7 signaling was determined in various cell types among peripheral blood mononuclear cells from healthy controls and SLE patients. The effects of Pin1 and TLR signaling on SLE development were determined using validated Pin1 short hairpin RNA (shRNA), Pin1 genetic knockout, and the small-molecule Pin1 inhibitor all- trans-retinoic acid (ATRA) in immune cells and in several strains of lupus-prone mice. Results We found abnormal activation of Pin1 and its downstream targets IRAK-1 and IRF-7 in SLE patients. Furthermore, inhibition of Pin1 using either validated Pin1 shRNA or ATRA blocked TLR-7-induced activation of IRAK-1 and IRF-7 in SLE patient-derived immune cells. Moreover, in multiple lupus-prone animals, both Pin1 knockout and ATRA strikingly attenuated the expression of autoimmunity, including skin lesions, lymphadenopathy, splenomegaly, glomerulonephritis, proteinuria, and production of anti-double-stranded DNA antibodies and CD4−CD8− T cells, and also prolonged overall survival in MRL/ lpr and B6. lpr mice. Conclusion Pin1 plays a critical role in the development of SLE, and Pin1-targeted therapy offers a promising new strategy for treating SLE. [ABSTRACT FROM AUTHOR]

Objective The disease process in rheumatoid arthritis (RA) starts years before the clinical diagnosis is made, and elevated levels of disease-specific autoantibodies can be detected during this period. Early responses to known or novel autoantigens likely drive the eventual production of pathogenic autoimmunity. Importantly, the presence of disease-specific autoantibodies can identify individuals who are at high risk of developing RA but who do not currently have arthritis. The goal of the current study was to characterize plasmablasts from individuals at risk of developing RA. Methods We investigated antibody-secreting plasmablasts derived from a well-characterized cohort of individuals who were at risk of developing RA, based on RA-related serum autoantibody positivity, as compared to patients with early (<1 year) seropositive RA as well as healthy control subjects. The plasmablast antibody repertoires of at-risk subjects were analyzed using DNA barcode-based methods with paired heavy- and light-chain gene sequencing. Cells were single-cell sorted, the cell- and plate-specific DNA barcodes were sequentially added, and next-generation sequencing was performed. Results Total plasmablast levels were similar in the antibody-positive (1%) and control (0.4-1.6%) groups. However, increased frequencies of IgA+ versus IgG+ plasmablasts were observed in the antibody-positive group (39% IgA+ and 37% IgG+) as compared to other groups (1-9% IgA+ and 71-87% IgG+). Paired antibody sequences from antibody-positive subjects revealed cross-isotype clonal families and similar sequence characteristics in the IgA and IgG plasmablast repertoires. Antibody-positive individuals also demonstrated elevated serum levels of IgA isotype anti-cyclic citrullinated peptide 3 antibodies. Conclusion The IgA plasmablast dominance in these antibody-positive individuals suggests that a subset of RA-related autoantibodies may arise from mucosal immune responses and may be involved in early disease pathogenesis in individuals who are at risk of developing RA. [ABSTRACT FROM AUTHOR]

Objective To determine the effect of alendronate (ALN) and teriparatide on trabecular bone score (TBS) in patients with glucocorticoid-induced osteoporosis. Methods Patients with chronic glucocorticoid therapy-induced osteoporosis (median 7.5 mg/day prednisone equivalent for ≥90 days) were randomized to receive oral ALN 10 mg/day (n = 214) or subcutaneous teriparatide 20 μg/day (n = 214) for 36 months; 118 patients in the ALN group and 123 patients in the teriparatide group completed treatment. Dual x-ray absorptiometry (DXA) results for 53 patients receiving ALN and 56 patients receiving teriparatide who had DXA scans with adequate resolution to perform TBS analysis and completed 36 months of therapy were blindly analyzed for TBS at baseline and 3, 6, 12, 18, 24, and 36 months. Results In teriparatide-treated patients, TBS was significantly increased at 18 months compared to baseline, and by 36 months had increased 3.7% ( P < 0.05). In ALN-treated patients, there was not a significant change in TBS compared to baseline at any time point. Changes in lumbar spine bone mineral density (BMD) measured by DXA in the subgroup with TBS data were similar to BMD results in the overall study population. At 36 months, increases in lumbar spine BMD were 5.5% and 10.3% in patients treated with ALN and teriparatide, respectively. Conclusion In patients with glucocorticoid-induced osteoporosis, both ALN and teriparatide increased lumbar spine BMD. However, trabecular bone score significantly increased with teriparatide but did not significantly change with ALN. The pathogenesis of glucocorticoid-induced osteoporosis is predominantly reduced bone formation. TBS may represent a sensitive measure to discriminate treatment effects of an anabolic versus an antiresorptive drug in glucocorticoid-induced osteoporosis. [ABSTRACT FROM AUTHOR]

Objective Emerging evidence supports a crucial role of myeloid-derived suppressor cells (MDSCs) in the regulation of autoimmune diseases. However, their role in systemic lupus erythematosus (SLE) remains unknown. This study sought to address the role of MDSCs in the pathogenesis of SLE. Methods MDSCs from (NZB × NZW)F1 lupus-prone mice were assessed for phenotype by flow cytometry, and the function of MDSCs was analyzed by in vitro T cell proliferation assay and real-time quantitative polymerase chain reaction. Extracellular trap (ET) formation was evaluated by immunofluorescence and confocal microscopy. The production of reactive oxygen species (ROS) by Ly-6G+ cells was determined by fluorescence-activated cell sorting analysis. Results Expansion of MDSCs was impaired and the function of MDSCs was defective in the lymphoid organs of (NZB × NZW)F1 lupus-prone mice with established disease, in which involvement of predominantly the granulocytic MDSC (G-MDSC) cell subset was observed. More specifically, the results showed that increased elimination of G-MDSCs, driven by the inflammatory milieu of lupus, could be attributed to ET formation, and that cytokines, such as interferon-α (IFNα), IFNγ, and interleukin-6, play a role in this process. Induction of ET release by G-MDSCs was mediated by the production of ROS, since inhibition of ROS generation significantly reduced ET release. Conclusion Collectively, the results of this study reveal that elimination of a crucial regulatory immune cell subset is a feature of the SLE microenvironment. These findings provide new insights into the pathogenetic mechanisms of the disease. [ABSTRACT FROM AUTHOR]

Integrating the perspectives of psychological contract and sex differences, this study examines how organizational decision to reduce labour costs influences employees' perceived psychological contract breach and their commitment to their organizations. Using two experiments, we found three-way interaction effects among the decision to reduce labour costs, employee sex, and the managerial control over the decision. The decision of labour costs reduction leads to stronger feelings of psychological contract breach for females when the decision is in low than in high levels of managerial control, but the same decision leads to stronger psychological contract breach for males when the decision is in high than in low levels of managerial control. Furthermore, the indirect effect of labour costs reduction on employees' organizational commitment through psychological contract breach is also contingent upon the interaction between employee sex and managerial control. Our findings expand the literature of psychological contract and shed light on timely practical issues of management's decisions regarding labour costs reduction. Practitioner points Labour costs reductions in economic downturns lead to different responses from employees, and managers are advised to plan their actions bearing in mind such differences., Management in crisis or difficulties calls for more delicate considerations of employees' psychological feelings towards the organization., Nuanced empirical evidence informs us about the different needs and responses of a diverse group of employees and how their responses contradict. [ABSTRACT FROM AUTHOR]

The article presents the study that explores on the use of haematopoietic stem cell transplantation (SCT) in the treatment of Fanconi anemia (FA) patients in Canada and the U.S. The topics discussed include the attributes of FA, the factors that influenced the decision making of FA patients and family members on SCT, and the benefits and probable risks of SCT.

Quantitative analyses of the macronutrient content of eight popular commercial 'ready-to-feed' baby meals for 6-9-month old infants in the UK market have been undertaken in order to ascertain their nutritional suitability in relation to the total daily dietary intake as well as nutritional profiling of the products. The chemical analyses conducted included Kjeldhal for protein, acid hydrolysis and extraction for fat, phenol sulphuric acid for carbohydrate and Association of Official Analytical Chemists 985.29 for fibre. The only difference found between different varieties (meat- and vegetable-based) was with respect to the protein content ( P = 0.04) per 100 g of food. The experimentally determined concentrations of macronutrients (g/100 kcal) were compared with the declared values provided by the manufacturers on the product labels and, despite some variations, the values obtained comply with regulatory requirements ( Commission Directive 2006/125/ EC). The total daily intake of fat (27.0 g per day) - based on the menu composed from commercial complementary food - is suggested to exceed the daily recommended values for fat (31%), if the intake of snacks and desserts are incorporated. These findings imply that the formulation of recipes, based on a standard commercial menu, is an important consideration in relation to the nutritional quality of the diet of infants. [ABSTRACT FROM AUTHOR]

Objective To define and characterize the progression of the spontaneous autoimmune disease that develops in mice in the absence of the leukocyte adhesion receptor P-selectin glycoprotein ligand 1 (PSGL-1). Methods Skin-resident immune cells from PSGL-1-deficient mice and C57BL/6 control mice of different ages were isolated and analyzed by flow cytometry. Biochemical parameters were analyzed in mouse serum and urine, and the presence of serum autoantibodies was investigated. Skin and internal organs were extracted, and their structure was analyzed histologically. Results Skin-resident innate and adaptive immune cells from PSGL-1−/− mice had a proinflammatory phenotype with an imbalanced T effector cell:Treg cell ratio. Sera from PSGL-1−/− mice had circulating autoantibodies commonly detected in connective tissue-related human autoimmune diseases. Biochemical and histologic analysis of skin and internal organs revealed skin fibrosis and structural and functional abnormalities in the lungs and kidneys. Furthermore, PSGL-1−/− mice exhibited vascular alterations, showing loss of dermal vessels, small vessel medial layer remodeling in the lungs and kidneys, and ischemic processes in the kidney that promote renal infarcts. Conclusion Our study demonstrates that immune system overactivation due to PSGL-1 deficiency triggers an autoimmune syndrome with characteristics similar to systemic sclerosis, including skin fibrosis, vascular alterations, and systemic organ involvement. These results suggest that PSGL-1 expression contributes to the maintenance of the homeostasis of the immune system and could act as a barrier for autoimmunity in mice. [ABSTRACT FROM AUTHOR]

Objective To determine interrelationships between the expression of long intergenic (noncoding) RNA-p21 (lincRNA-p21), NF-κB activity, and responses to methotrexate (MTX) in rheumatoid arthritis (RA) by analyzing patient blood samples and cell culture models. Methods Expression levels of long noncoding RNA and messenger RNA (mRNA) were determined by quantitative reverse transcription-polymerase chain reaction. Western blotting and flow cytometry were used to quantify levels of intracellular proteins. Intracellular NF-κB activity was determined using an NF-κB luciferase reporter plasmid. Results Patients with RA expressed reduced basal levels of lincRNA-p21 and increased basal levels of phosphorylated p65 (RelA), a marker of NF-κB activation. Patients with RA who were not treated with MTX expressed lower levels of lincRNA-p21 and higher levels of phosphorylated p65 compared with RA patients treated with low-dose MTX. In cell culture using primary cells and transformed cell lines, MTX induced lincRNA-p21 through a DNA-dependent protein kinase catalytic subunit (DNA PKcs)-dependent mechanism. Deficiencies in the levels of PRKDC mRNA in patients with RA were also corrected by MTX in vivo. Furthermore, MTX reduced NF-κB activity in tumor necrosis factor α-treated cells through a DNA PKcs-dependent mechanism via induction of lincRNA-p21. Finally, we observed that depressed levels of TP53 and lincRNA-p21 increased NF-κB activity in cell lines. Decreased levels of lincRNA-p21 did not alter NFKB1 or RELA transcripts; rather, lincRNA-p21 physically bound to RELA mRNA. Conclusion Our findings support a model whereby depressed levels of lincRNA-p21 in RA contribute to increased NF-κB activity. MTX decreases basal levels of NF-κB activity by increasing lincRNA-p21 levels through a DNA PKcs-dependent mechanism. [ABSTRACT FROM AUTHOR]

Objective Rituximab (RTX), an anti-CD20 monoclonal antibody, is highly effective in the treatment of several autoimmune diseases. The mechanism by which RTX treatment improves rheumatoid arthritis and antineutrophil cytoplasmic antibody-associated vasculitis is not easily related to B cell depletion alone. Prior studies have shown that RTX mediates a rapid stripping of CD20 and CD19 from the human B cell through a process known as trogocytosis. The aim of the present study was to investigate whether changes in B cell phenotype resulting from trogocytosis would diminish the ability of B cells to promote autoimmune disease. Methods Human peripheral blood mononuclear cells were cultured with RTX under conditions that permitted trogocytosis. Changes in B cell phenotype and cytokine production were measured in the basal state and under conditions of activation with interleukin-4 (IL-4)/anti-CD40. The effects of RTX were characterized in terms of a requirement for interaction with the Fcγ receptor (FcγR) and other Fc-dependent interactions. Results Trogocytosis induced a marked loss of surface CD19, IgD, CD40, and B cell-activating factor receptor, but did not alter induction of CD86 expression on purified B cells following IL-4/anti-CD40 treatment. Unexpectedly, RTX-dependent trogocytosis of normal human B cells in vitro led to a rapid up-regulation of IL-6 production, with no effect on the production of tumor necrosis factor α, IL-1β, interferon-γ, or IL-10. This effect was Fc-dependent and required the presence of an FcγR-bearing cell. Moreover, this effect involved the release of preformed intracellular IL-6 protein, as well as marked increases in IL-6 messenger RNA levels. Conclusion RTX-mediated trogocytosis of B cells in vitro results in acute production and release of IL-6. The nature of this effect and how it is related to the acute infusion reactions seen with RTX administration remain to be determined. [ABSTRACT FROM AUTHOR]

Objective Colony-stimulating factor 1 receptor (CSF-1R) essentially modulates monocyte proliferation, migration, and activation, which are considered important for the pathogenesis of rheumatoid arthritis (RA). We undertook this study to determine CSF-1R expression in human RA as well as the efficacy of a specific anti-CSF-1R monoclonal antibody (AFS98) in 2 different animal models of RA. Methods CSF-1R expression was examined in blood, synovium, and bone samples from RA patients, osteoarthritis (OA) patients, and healthy subjects. The efficacy of AFS98 was examined by clinical assessment, histology, and bone histomorphometry in collagen-induced arthritis (CIA) and serum-transfer arthritis. Results CSF-1R expression was increased in the synovium of RA patients compared to OA patients and healthy controls in fibroblast-like synoviocytes, follicular dendritic cells, macrophages, and osteoclasts. Circulating RA monocytes and neutrophils but not lymphocytes were CSF-1R+. In mice, blockade of CSF-1R abrogated cartilage damage, bone erosion, and systemic bone loss, and this was associated with the depletion of osteoclasts in both models. While blockade of CSF-1R did not affect inflammation in passive serum-transfer arthritis, it significantly reduced inflammation in CIA, and this was associated with the absence of synovial macrophages and reduced splenic CD11b+Gr-1− monocytes. Conclusion CSF-1R was broadly expressed in human RA. Blockade of CSF-1R protected against bone and cartilage destruction in both mouse models and also showed significant antiinflammatory effects in the CIA model. These data provide evidence for CSF-1R as a therapeutic target in RA. [ABSTRACT FROM AUTHOR]

In this study, we investigate the effect of manuka honey-impregnated dressings (MHID) on the healing of neuropathic diabetic foot ulcers (NDFU). A total of 63 Caucasians, type 2 diabetic patients followed up in the diabetic foot outpatient clinic comprised the study population. Patients were randomised in two groups as follows: group I patients were treated with MHID and group II patients were treated with conventional dressings (CD). The patients were followed up on a weekly basis for 16 weeks. Mean healing time was 31 ± 4 days in group I versus 43 ± 3 days in group II ( P < 0·05). In group I patients 78·13% of ulcers became sterile during the first week versus 35·5% in group II patients; the corresponding percentages for weeks 2, 4 and 6 were 15·62% versus 38·7%, 6·25% versus 12·9% and 0% versus 12·9% respectively. The percent of ulcers healed did not differ significantly between groups (97% for MHID and 90% for CD). MHID represent an effective treatment for NDFU leading to a significant reduction in the time of healing and rapid disinfection of ulcers. [ABSTRACT FROM AUTHOR]

Objective Rheumatoid arthritis (RA) is an inflammatory autoimmune disease characterized by severe joint erosion and systemic osteoporosis. Chronic T cell activation is a hallmark of RA, and agents that target the CD28 receptor on T cells, which is required for T cell activation, are being increasingly used as therapies for RA and other inflammatory diseases. Lymphocytes play complex roles in the regulation of the skeleton, and although activated T cells and B cells secrete cytokines that promote skeletal decline, under physiologic conditions lymphocytes also have key protective roles in the stabilization of skeletal mass. Consequently, disruption of T cell costimulation may have unforeseen consequences for physiologic bone turnover. This study was undertaken to investigate the impact of pharmacologic CD28 T cell costimulation blockade on physiologic bone turnover and structure. Methods C57BL6 mice were treated with CTLA-4Ig, a pharmacologic CD28 antagonist or with irrelevant control antibody (Ig), and serum biochemical markers of bone turnover were quantified by enzyme-linked immunosorbent assay. Bone mineral density and indices of bone structure were further measured by dual x-ray absorptiometry and micro-computed tomography, respectively, and static and dynamic indices of bone formation were quantified using bone histomorphometry. Results Pharmacologic disruption of CD28 T cell costimulation in mice significantly increased bone mass and enhanced indices of bone structure, a consequence of enhanced bone formation, concurrent with enhanced secretion of the bone anabolic factor Wnt-10b by T cells. Conclusion Inhibition of CD28 costimulation by CTLA-4Ig promotes T cell Wnt-10b production and bone formation and may represent a novel anabolic strategy for increasing bone mass in osteoporotic conditions. [ABSTRACT FROM AUTHOR]

Objective Rebamipide, a gastroprotective agent, has the ability to scavenge reactive oxygen radicals. Increased oxidative stress is implicated in the pathogenesis of rheumatoid arthritis (RA). We undertook this study to investigate the impact of rebamipide on the development of arthritis and the pathophysiologic mechanisms by which rebamipide attenuates arthritis severity in a murine model of RA. Methods Collagen-induced arthritis (CIA) was induced in DBA/1J mice. Anti-type II collagen antibody titers and interleukin-17 (IL-17) levels were determined using enzyme-linked immunosorbent assay. The expression of transcription factors was analyzed by immunostaining and Western blotting. Frequencies of IL-17-producing CD4+ T cells (Th17 cells) and CD4+CD25+FoxP3+ Treg cells were analyzed by flow cytometry. Results Rebamipide reduced the clinical arthritis score and severity of histologic inflammation and cartilage destruction in a dose-dependent manner. The joints isolated from rebamipide-treated mice with CIA showed decreased expression of nitrotyrosine, an oxidative stress marker. Rebamipide-treated mice showed lower circulating levels of type II collagen-specific IgG, IgG1, and IgG2a. Whereas the number of Th17 cells in spleens was decreased in rebamipide-treated mice with CIA, a significant increase in the number of Treg cells in spleens was observed. In vitro, rebamipide inhibited Th17 cell differentiation through STAT-3/retinoic acid receptor-related orphan nuclear receptor γt and reciprocally induced Treg cell differentiation through FoxP3. Rebamipide increased Nrf2 nuclear activities in murine CD4+ T cells and LBRM-33 murine T lymphoma cells. Heme oxygenase 1 (HO-1) expression in the spleens was markedly increased in rebamipide-treated mice. Conclusion The inhibitory effects of rebamipide on joint inflammation are associated with recovery from an imbalance between Th17 cells and Treg cells and with activation of an Nrf2/HO-1 antioxidant pathway. [ABSTRACT FROM AUTHOR]

Background Transtheoretical Model of change has been used successfully in promoting behaviour change. Objective To examine the relationships between health-related quality of life (HRQoL) scores with the stages of change of adequate physical activity and fruit and vegetables intake. Design This was a cross-sectional study conducted among employees of the main campus and Engineering campus of Universiti Sains Malaysia (USM) during October 2009 and March 2010. Main variables studied: Data on physical activity and fruit and vegetable intake was collected using the WHO STEPS instrument for chronic disease risk factors surveillance. The Short Form-12 health survey (SF-12) was used to gather information on participants' HRQoL. The current stages of change are measured using the measures developed by the Pro-Change Behaviour Systems Incorporation. Statistical analysis: One way ANOVA and its non-parametric equivalent Kruskal-Wallis were used to compare the differences between SF-12 scores with the stages of change. Results A total of 144 employees were included in this analysis. A large proportion of the participants reported inadequate fruits and vegetable intake (92.3%) and physical activity (84.6%). Mean physical and mental component scores of SF-12 were 50.39 (SD = 7.69) and 49.73 (SD = 8.64) respectively. Overall, there was no statistical significant difference in the SF-12 domains scores with regards to the stages of change for both the risk factors. Conclusions There were some evidence of positive relationship between stages of change of physical activity and fruit and vegetable intake with SF-12 scores. Further studies need to be conducted to confirm this association. [ABSTRACT FROM AUTHOR]

Objective Glycosphingolipids (GSLs) are ubiquitous membrane components that modulate transmembrane signaling and mediate cell-to-cell and cell-to-matrix interactions. GSL expression is decreased in the articular cartilage of humans with osteoarthritis (OA). This study was undertaken to determine the functional role of GSLs in cartilage metabolism related to OA pathogenesis in mice. Methods We generated mice with knockout of the chondrocyte-specific Ugcg gene, which encodes an initial enzyme of major GSL synthesis, using the Cre/loxP system (Col2- Ugcg−/− mice). In vivo OA and in vitro cartilage degradation models were used to evaluate the effect of GSLs on the cartilage degradation process. Results Although Col2- Ugcg−/− mice developed and grew normally, OA changes in these mice were dramatically enhanced with aging, through the overexpression of matrix metalloproteinase 13 and chondrocyte apoptosis, compared to their wild-type (WT) littermates. Col2- Ugcg−/− mice showed more severe instability-induced pathologic OA in vivo and interleukin-1α (IL-1α)-induced cartilage degradation in vitro. IL-1α stimulation of chondrocytes from WT mice significantly increased Ugcg messenger RNA expression and up-regulated GSL metabolism. Conclusion Our results indicate that GSL deficiency in mouse chondrocytes enhances the development of OA. However, this deficiency does not affect the development and organization of cartilage tissue in mice at a young age. These findings indicate that GSLs maintain cartilage molecular metabolism and prevent disease progression, although GSLs are not essential for chondrogenesis of progenitor and stem cells and cartilage development in young mice. GSL metabolism in the cartilage is a potential target for developing a novel treatment for OA. [ABSTRACT FROM AUTHOR]

Objective To determine the role of CCL21 and its receptor CCR7 in the pathogenesis of rheumatoid arthritis (RA). Methods Histologic studies were performed to compare the expression of CCR7 and CCL21 in RA synovial tissue. Next, the role of CCL21 and/or CCR7 in angiogenesis was examined using in vitro chemotaxis, tube formation, and in vivo Matrigel plug assays. Finally, the mechanism by which CCL21 mediates angiogenesis was determined by Western blot analysis and endothelial cell chemotaxis and tube formation assays. Results CCL21, but not CCL19, at concentrations present in the RA joint, induced human microvascular endothelial cell (HMVEC) migration that was mediated through CCR7 ligation. Suppression of the phosphatidylinositol 3-kinase pathway markedly reduced CCL21-induced HMVEC chemotaxis and tube formation; however, suppression of the ERK and JNK pathways had no effect on these processes. Neutralization of either CCL21 in RA synovial fluid or CCR7 in HMVECs significantly reduced the induction of HMVEC migration and/or tube formation by RA synovial fluid. We further demonstrated that CCL21 is angiogenic, by showing its ability to promote blood vessel growth in Matrigel plugs in vivo at concentrations that are present in RA joints. Conclusion Angiogenesis is dependent on endothelial cell activation, migration, and proliferation, and inhibition of angiogenesis may provide a novel therapeutic approach in RA. This study identified a novel function of CCL21 as a mediator of RA angiogenesis, supporting CCL21/CCR7 as a therapeutic target in RA. [ABSTRACT FROM AUTHOR]

In China, a full fat soy powder mixed with multiple micronutrient powders ( Ying Yang Bao (YYB)) was developed, and the efficacy of YYB was shown in controlling anaemia and improving child growth and development. However, prior to 2008, there was no sustainable way to provide YYB to vulnerable populations, except through free distribution by the government. This study was to test the concept of public-private partnership (PPP) to deliver YYB and to evaluate the effectiveness of marketing YYB through PPP. Programme activities included development of a complementary food supplement (CFS) national standard, product concept test, product development and marketing, behavior change communication, monitoring and evaluation. Baseline and end-line surveys were used to evaluate product awareness, purchasing and the impacts of the project on anaemia and feeding practices. A Chinese CFS standard was approved. Caregivers and their 6- to-24-month-old children participated in the baseline ( n = 226) and the end-line survey ( n = 221). A concept test at the baseline survey showed that 78% of caregivers were willing to buy YYB at 0.1 USD. After developing the product and implementing the intervention for 8 months, 59.6% of surveyed caregivers purchased YYB. While not significant, the prevalence of anaemia was marginally lower at the end line (28.8%) than at the baseline (36.2%). For those purchasing YYB, the risk of anaemia was significantly reduced by 87% of odds ( P < 0.009). The end-line survey found that feeding practices had improved significantly following the intervention. An enabling policy and regulatory environment in which CFSs are defined and parameters for appropriate marketing are identified as a prerequisite for marketing YYB or other nutritious CFS. Public and private advocacy and marketing could successfully increase awareness of YYB and access and use through market channels. The YYB project may be effective for reducing anaemia and improving feeding practices. [ABSTRACT FROM AUTHOR]

Human immunodeficiency virus (HIV)-infected children generally show poor growth. Episodes of diarrhoea and pneumonia in HIV-infected children are thought to be more severe than in HIV-uninfected children. The objective of this study was to compare duration of hospitalization, appetite and nutritional status of HIV-infected children with that of uninfected children. A cross-sectional study was performed on children (2-24 months) admitted with diarrhoea or pneumonia to the university hospital. Children were tested for HIV, and the duration of hospitalization was noted for 189 children. Follow-up for blood analysis ( n = 154) and appetite measurement ( n = 48) was performed 4-8 weeks after discharge. Appetite was measured as ad libitum intake of a commercial infant cereal using highly standardized procedures. Hospitalization (in days) was significantly longer in HIV-infected children; among children admitted with diarrhoea (5.9 ± 1.9 vs. 3.8 ± 1.5) (mean ± standard deviation) and with pneumonia (9.0 ± 2.5 vs. 5.9 ± 1.9). Serum zinc, iron and transferrin concentrations, and haemoglobin levels were significantly lower in HIV-infected children compared with uninfected children. Appetites [amounts eaten (g) per kg body weight] of HIV-infected children were significantly poorer than those of HIV-uninfected children (18.6 ± 5.8 vs. 25.2 ± 7.4). The eating rates (g min) of HIV-infected children were also slower (17.6 ± 6.2 vs. 10.1 ± 3.7) Mean Z-scores for length-for-age were significantly lower among HIV-infected children compared with HIV-uninfected children. Weight-for-length Z-scores were not significantly different. In summary, HIV-infected children had a 55% longer duration of hospitalization and a 21% lower appetite. [ABSTRACT FROM AUTHOR]

Objectives: Rotating residents represent a significant proportion of housestaff in academic emergency departments (EDs), yet they rarely receive targeted didactic education during their emergency medicine (EM) rotations. The goals of this study were: 1) to determine the effectiveness of an online didactic curriculum in improving EM knowledge among rotating residents and 2) to assess rotating resident satisfaction with this curriculum. Methods: The authors created an online lecture series of six EM subject areas targeted to rotating residents called the Northwestern University Rotating Resident Curriculum (NURRC). All rotating residents at the study site were eligible, written consent was obtained, and the study was approved by the institutional review board. Consenting participants were pretested with a 42-question multiple-choice examination and then randomized to two groups: one with access to the NURRC during the first 2 weeks of the rotation (experimental) and one without (control). Halfway through the rotation, all participants were posttested with a different multiple-choice examination, and the controls were then granted NURRC access. The primary outcome was the difference between pretest and posttest scores (score delta). The t-test was used to compare mean scores, and a linear regression model was used to determine the association of NURRC access on score delta after adjustment for pretest type and resident type. A postintervention survey was administered at the end of the rotation to assess satisfaction with the NURRC and collect suggestions for improvement. Results: Fifty-four rotating residents were enrolled: 29 in the experimental group and 25 in the control group. There was no significant difference in pretest scores between the two groups. Mean score delta was 17.3% in the experimental group and 1.6% in the control group, an absolute difference of 15.7% (95% confidence interval [CI] = 10% to 22%). After adjustment for resident type and pretest type, the only variable positively associated with the primary outcome was NURRC access. Third-year and preliminary- year internal medicine (IM) residents demonstrated the greatest absolute improvement in score delta when granted NURRC access. Eighty percent of the participants responded to the satisfaction survey. Over 80% of the survey respondents approved of each component lecture and of the NURRC overall. Conclusions: After exposure to an online didactic curriculum, rotating residents demonstrated a significant increase in EM knowledge and reported a high level of satisfaction with the didactic program. [ABSTRACT FROM AUTHOR]

Sexually experienced women are at risk of cervical cancer, one of the most common female reproductive cancers. Nearly 20% of U.S. women aged 18-64 have a disability, and disability is associated with health care access; however, the relationship between disability and Pap smear receipt remains underexplored. Data on 20,907 women aged 21-64 from the 2000 and 2005 National Health Interview Surveys were used to investigate the relationship between disability and cervical cancer screening. Logistic regression analyses were conducted to assess the association between disability and both women's receipt of a Pap smear and their receipt of a doctor's recommendation for a Pap smear in the past year. Having a disability was negatively associated with Pap smear receipt (odds ratio, 0.6). Compared with women with no disabilities, those with mobility limitations and those with other types of limitations had reduced odds of having received a Pap smear (0.5-0.7). Disability was positively associated with having received a recommendation for a Pap smear (1.2); however, among women who had received a recommendation, those with disabilities had reduced odds of having received a Pap smear (0.5). Among women who had not received a Pap smear, 31% of those with disabilities and 13% of others cited cost or lack of insurance as the primary reason. The negative relationship between Pap smear receipt and multiple types of disability suggests barriers beyond the human-made physical features of the environment. Efforts to reduce inequalities in reproductive health care access should consider the needs of women with disabilities. [ABSTRACT FROM AUTHOR]

ACADEMIC EMERGENCY MEDICINE 2010; 17:940–950 © 2010 by the Society for Academic Emergency Medicine Objectives: The objectives of this study were to determine concordance of emergency department (ED) management of acute myocardial infarction (AMI) with guideline recommendations and to identify ED and patient characteristics predictive of higher guideline concordance. Methods: The authors conducted a chart review study of ED AMI care as part of the National Emergency Department Safety Study (NEDSS). Using a primary hospital discharge diagnosis of AMI (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM], codes 410.XX), a random sample of ED visits for AMI in 58 urban EDs across 20 U.S. states between 2003 and 2006 were identified. Concordance with American College of Cardiology/American Heart Association (ACC/AHA) guideline recommendations was evaluated using five individual quality measures and a composite concordance score. Concordance scores were calculated as the percentage of eligible patients who received guidelines-recommended care. These percentage scores were rescaled from 0 to 100, with 100 indicating perfect concordance. Results: The cohort consisted of 3,819 subjects; their median age was 65 years, and 62% were men. The mean (± standard deviation [SD]) ED composite concordance score was 61 ± 8), with a broad range of values (42 to 84). Except for aspirin use (mean concordance, 82), ED concordance scores were low (beta-blocker use, 56; timely electrocardiogram [ECG], 41; timely fibrinolytic therapy, 26; timely ED disposition for primary percutaneous coronary intervention [PCI] candidates, 43). In multivariable analyses, older age (beta-coefficient per 10-year increase, −1.5; 95% confidence interval [CI] = −2.4 to −0.5) and southern EDs (beta-coefficient, −5.2; 95% CI = −9.6 to −0.9) were associated with lower guideline concordance, whereas ST-segment elevation on initial ED ECG was associated with higher guideline concordance (beta-coefficient, 3.6; 95% CI = 1.5 to 5.7). Conclusions: Overall ED concordance with guideline-recommended processes of care was low to moderate. Emergency physicians should continue to work with other stakeholders in AMI care, such as emergency medical services (EMS) and cardiologists, to develop strategies to improve care processes. [ABSTRACT FROM AUTHOR]

This study evaluated the nutritional status of lactating women with regard to vitamins A and E and the relationship between dietary intake and concentrations in serum and milk. A longitudinal study was conducted with 43 women at a hospital in northeastern Brazil. Blood and milk samples and food intake recalls were obtained at three moments during the breastfeeding period. Retinol and alpha‐tocopherol were analysed by high‐performance liquid chromatography. Dietary inadequacy was analysed according to the estimated average requirement, with intrapersonal variation adjusted by the multiple source method. Food intake was classified by quartiles of consumption. Serum retinol was 1.65 μmol/L, with 5% of low concentrations (<0.7 μmol/L) at the first collection. Serum alpha‐tocopherol decreased from 30.18 to 25.49 μmol/L at the third collection (P = 0.008), with an increase in the percentage frequency of deficiency (<12 μmol/L). Both vitamins maintained stable concentrations in milk at the different collection times, and the overall dietary inadequacy of vitamins A and E was 58% and 100%, respectively. There was a correlation only between vitamin A intake and serum retinol (r = 0.403, P = 0.007), and higher retinol concentrations were found in women classified in the highest consumption quartile (P = 0.031). Over the course of lactation, there was a high degree of inadequacy in vitamin intake and a reduction in serum alpha‐tocopherol, whereas its concentrations in milk remained unchanged. Dietary intake of vitamin A has been shown to influence serum retinol, which underscores the importance of adequate nutrition and monitoring of vitamin deficiency during lactation. [ABSTRACT FROM AUTHOR]

The objective of this study was to assess plasma fatty acid (FA) patterns of 6‐month‐old South African infants and to determine their association with feeding practices, growth, and psychomotor development. Plasma total phospholipid FA composition (% of total FAs) of 6‐month‐old infants (n = 353) from a peri‐urban township was analysed, and principal component and factor analysis were performed to identify plasma FA patterns. Feeding practices, anthropometric measurements, and psychomotor development scores were determined. Four major plasma phospholipid FA patterns were identified: A plant‐based C18 FA, a high n‐6 long‐chain polyunsaturated fatty acids (LCPUFA), a C16:1 and long‐chain saturated fatty acid (SFA), and a high n‐3 and low n‐6 LCPUFA pattern. Formula feeding was associated with higher, whereas breastfeeding was associated with lower scores for the plant‐based C18 FA and C16:1 and long‐chain SFA patterns. On the other hand, breastfeeding, the consumption of cow's milk, and the consumption of semisolid foods were associated with higher scores, whereas formula feeding was associated with lower scores for the high n‐6 LCPUFA pattern. Breastfeeding and the consumption of semisolids were also associated with higher high n‐3 and low n‐6 LCPUFA pattern scores. The C16:1 and long‐chain SFA and high n‐3 and low n‐6 LCPUFA patterns were positively associated with psychomotor development scores. In 6‐month‐old South African infants, we identified distinct plasma FA patterns that presumably represent the FA quality of their diet and that are associated with psychomotor development. Our results suggest that breast milk is an important source of n‐6 LCPUFAs and formula‐fed infants may be at risk of inadequate LCPUFA intake. [ABSTRACT FROM AUTHOR]

Monitoring pregnancy weight can reduce excess gestational weight gain (GWG), and is recommended in clinical practice guidelines as part of routine care. This study aimed to evaluate the implementation of routine weight monitoring using a pregnancy weight gain chart (PWGC), and assess health care professionals (HCPs) and pregnant women's attitudes and practices around its use. A semiquantitative survey was conducted with a consecutive sample of antenatal women at 16 and 36 weeks gestation. Women were weighed, and a PWGC audit done at 36 weeks gestation to assess adherence to chart use and GWG. A cross‐sectional survey of antenatal HCPs at the Australian facility assessed staff attitudes and practices relating to weight monitoring and PWGC use. Of the 291 women surveyed, 68% reported being given a PWGC. Of the audited PWGCs (n = 258), 54% had less than three weights recorded, 36% had errors, and 3% were unused. All HCPs surveyed (n = 42) were aware of the PWGC, 63% reported using it to track GWG regularly and 26% believed it to be only the woman's responsibility (i.e., not the midwife's role) to complete it. Seventy‐six percent reported they needed more training in counselling pregnant women, and insufficient time was a main barrier to weighing and conversing with women. It is feasible to implement a PWGC into routine antenatal care. Clarity over women's and HCPs responsibility for monitoring GWG and completion of the PWGC is needed. Training on correct PWGC use and counselling and workforce engagement are required to overcome barriers and support healthy GWG. [ABSTRACT FROM AUTHOR]

Vitamin D deficiency has adverse health effects in young children. Our aims were to determine predictors of vitamin D status and then to use these factors to develop a practical tool to predict low 25(OH)D concentrations in preschool New Zealand children. A cross-sectional sample of 1329 children aged 2 to <5 years were enrolled from throughout New Zealand in late-winter to spring 2012. 25-Hydroxyvitamin D (25(OH)D) was measured on dried blood spot (DBS) samples collected using finger-prick sampling. Caregivers completed a questionnaire. Mean (SD) DBS 25(OH)D concentration was 52(19)nmol/L. 25(OH)D < 25 nmol/L was present in 86(7%), 25(OH)D < 50 nmol/L in 642(48%), 25(OH)D 50- < 75 nmol/L in 541(41%) and 25(OH)D > 75 nmol/L in 146(11%) of children. Factors independently associated with the risk of 25(OH)D < 25 nmol/L were female gender (OR 1.92,95%CI 1.17-3.14), other non-European ethnicities (not including Māori or Pacific) (3.51,1.89-6.50), had olive-dark skin colour (4.52,2.22-9.16), did not take vitamin D supplements (2.56,1.06-6.18), had mothers with less than secondary-school qualifications (5.00,2.44-10.21) and lived in more deprived households (1.27,1.06-1.53). Children who drank toddler milk (vitamin D fortified cow's milk formula marketed to young children) had a zero risk of 25(OH)D < 25 nmol/L. The predictive tool identified children at risk of 25(OH)D < 25 nmol/L with sensitivity 42%, specificity 97% and ROC area-under-curve 0.76(95%CI 0.67-0.86, p < 0.001). Predictors of low vitamin D status were consistent with those identified in previous studies of New Zealand children. The tool had insufficient predictive ability for use in clinical situations, and suggests a need to promote safe, inexpensive testing to determine vitamin D status in preschool children. [ABSTRACT FROM AUTHOR]

It is recommended that infants from the age of 12 months should be weaned from bottles. However, an overwhelming proportion of young children were still using bottle after the recommended age of bottle-weaning. This cross-sectional study examined the association between utensils for milk drinking and food group consumption, growth and socio-demographic characteristics among young children. Data from the Survey of Infant and Young Child Feeding in Hong Kong were analyzed for 649 children aged 18-48 months old. Dietary outcomes were obtained via 3-day dietary records, while utensils for milk drinking and socio-demographic characteristics were collected from a self-developed questionnaire. Length/height and weight of the children were measured by the nurses. Results showed that daily consumption of formula milk was significantly greater among bottle users or bottle plus cup users than non-bottle users ( p < 0.05). Exclusive bottle users had significantly lower intakes of meat and meat alternatives than bottle plus cup users for the 18 to 24-month group ( p = 0.001) and lower intakes of fruits than non-bottle users in the 48-month group ( p = 0.015). BMI z-score was significantly higher for exclusive bottle users than non-bottle users, even after adjusting for socio-economic factors and child's age ( p = 0.006). The results showed that the milk drinking utensil was associated with the amount of formula milk and food group consumption as well as BMI z-score. There is a need to actively discourage prolonged bottle use in order to help young children develop good dietary habits. © 2016 John Wiley & Sons Ltd [ABSTRACT FROM AUTHOR]

Common mental disorders, such as depression and anxiety, affect approximately 16% of pregnant women in low- and middle-income countries. Food insecurity (FI) has been shown to be associated with depressive symptoms. It has also been suggested that the association between FI and depressive symptoms is moderated by social support (SS); however, there is limited evidence of these associations among pregnant women living in low-income and middle-income countries. We studied the association between FI and depressive symptoms severity and assessed whether such an association varied among Ugandan pregnant women with low vs. high SS. Cross-sectional data were collected among 403 pregnant women in northern Uganda. SS was assessed using an eight-item version of the Duke-UNC functional SS scale. FI and depressive symptoms were assessed by, respectively, the individually focused FI scale and the Center for Epidemiologic Studies-Depression scale. Women were categorized into two SS groups, based on scoring < or ≥ to the median SS value. Multivariate linear regression models indicated an independent association between FI and depressive symptoms severity. The association between FI and depressive symptoms severity was moderated by SS i.e. was stronger among women in the low SS category (adjusted beta (95%CI): 0.91 (0.55; 1.27)) than for women belonging to the high SS group (0.53 (0.28; 0.78)) (adjusted p value for interaction = 0.026). There is need for longitudinal or interventional studies among pregnant women living in northern Uganda or similar contexts to examine the temporal sequence of the associations among food insecurity, depressive symptoms severity and social support. © 2016 John Wiley & Sons Ltd [ABSTRACT FROM AUTHOR]

Nipple pain and damage are commonly experienced by breastfeeding women and are associated with negative breastfeeding outcomes. Health care providers often recommend the application of lanolin to treat painful/damaged nipples, yet no randomized controlled trial has evaluated the effectiveness of lanolin on nipple pain and breastfeeding outcomes. The purpose of this study was to evaluate the effect of lanolin on nipple pain among breastfeeding women with damaged nipples. A randomized, single-blind, controlled trial was conducted at a tertiary care hospital in Hamilton, Ontario, Canada. Breastfeeding women ( N = 186) identified as having nipple pain/damage were randomized to apply lanolin (intervention group; n = 93) or to receive usual postpartum care (control group; n = 93). The primary outcome was nipple pain at 4 days post-randomization measured by the Numeric Rating Scale. Additional outcomes included nipple pain measured by the Short Form McGill Pain Questionnaire, breastfeeding duration/exclusivity, breastfeeding self-efficacy, and maternal satisfaction with lanolin treatment versus usual care. The results revealed no significant group differences in mean pain scores at 4 days post-randomization. Women in both groups experienced clinically relevant decreases in nipple pain by 7 days post-randomization. Significantly, more women in the lanolin group reported that they were satisfied with treatment compared with those receiving usual care. No significant group differences were found for other secondary outcomes. While more women were satisfied using lanolin, its application to sore/damaged nipples was ineffective for reducing nipple pain or improving breastfeeding outcomes. [ABSTRACT FROM AUTHOR]