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Background Presence in the neonatal intensive care unit (NICU) is a vital step for caregivers initiating involvement, such as skin-to-skin contact, holding or singing/reading to their newborn. Little is known about caregiver presence and involvement in Canadian NICU's context by caregiver type (mother, father, other), and the association between maternal presence and key maternal and newborn characteristics. Purpose The primary objective was to examine the presence and involvement of family caregivers in the NICU. The secondary objective was to examine the relationship between maternal presence and maternal and newborn characteristics. Design and methods A prospective observational cohort study in an open bay setting of an Eastern Canadian NICU. Presence (physically present at the newborn's bedside) and involvement (e.g., skin-to-skin, singing/reading) were tracked daily by families in the NICU until discharge. Demographic information was also collected. Results Participants included 142 mothers and their newborns. Mothers were present 8.7 h/day, fathers were present 4.1 h/day, and other caregivers were present 1.8 h/day in the NICU in the first 34 days. Mothers were involved in care activities 50% of the time they were present in the NICU, whereas fathers and other caregivers were spending 20% and 6% of their time respectively. Regression identified maternal age, distance to home, parity, birthweight, and length of stay to be statistically significant variables related to maternal presence. Conclusions There is variation in presence and involvement by caregiver type. Targeted interventions to maintain and increase mothers, fathers and other caregivers' presence and involvement in care throughout their stay in the NICU are recommended.

Genome sequencing (GS) studies involving healthy children can advance scientific knowledge of genetic variation. Little research has examined primary care providers’ views on using GS in this context. This study explored primary care provider perspectives on the use of GS in research and the care of healthy children. We conducted semi-structured interviews with 16 providers discussing their views on GS research and receiving results. Interviews were analyzed by thematic analysis and constant comparison. Participants were family physicians (11/16) and primary care pediatricians (5/16) in practice for >10 years (11/16). Participants valued GS in healthy children for research purposes; however, opinions diverged on using the results in primary care. Proponents valued using results for surveillance and prevention in healthy children. Skeptics questioned the clinical utility of results and the appropriateness of applying research data in primary care. Both groups shared concerns over opportunistic screening, validity, and interpretation of results, increased health system costs and inequities, and genetic discrimination. Primary care providers were ambivalent about the appropriateness and utility of GS in the care of healthy children. Providers feel unprepared and unsure of their obligations in disclosing these results. Providers do not feel they are equipped with the necessary resources and training to support their patients in using GS results in their care.

Objective To evaluate the relationship between the timing of infant cereal introduction between 4 and 6 months of age and growth and dietary intake in later childhood. Study design A longitudinal cohort study was conducted among healthy children 0-10 years of age participating in The Applied Research Group for Kids cohort study between June 2008 and August 2019 in Toronto, Canada. Results Of 8943 children included, the mean (SD) age of infant cereal introduction was 5.7 (2.1) months. In the primary analysis, children who were introduced to infant cereal at 4 vs 6 months had 0.17 greater body mass index z score (95% CI 0.06-0.28; P = .002) and greater odds of obesity (OR 1.82; 95% CI 1.18-2.80; P = .006) at 10 years of age. In the secondary analysis, children who were introduced to infant cereal at 4 vs 6 months had 0.09 greater height-for-age z score (95% CI 0.04-0.15; P = .002) at 1 year of age, an association that was not observed at 5 or 10 years of age. Children who were introduced to infant cereal at 4 vs 6 months had greater nutrition risk which was primarily determined by a less-favorable eating behavior score at 18 months to 5 years of age (0.18 units higher; 95% CI 0.07-0.29; P = .001). Conclusions Introduction of infant cereal at 4 vs 6 months was associated with greater body mass index z score, greater odds of obesity, similar height-for-age z score, and less favorable eating behavior. These findings support recommendations for introducing solid food around 6 months of age.

Variants of uncertain significance (VUS) are frequently reclassified but recontacting patients with updated results poses significant resource challenges. We aimed to characterize public and patient preferences for being recontacted with updated results. A discrete choice experiment (DCE) was administered to representative samples of the Canadian public and cancer patients. DCE attributes were uncertainty, cost, recontact modality, choice of results, and actionability. DCE data were analyzed using a mixed logit model and by calculating willingness to pay (WTP) for types of recontact. Qualitative interviews exploring recontact preferences were analyzed thematically. DCE response rate was 60% (n = 1003, 50% cancer patient participants). 31 participants were interviewed (11 cancer patients). Interviews revealed that participants expected to be recontacted. Quantitatively, preferences for how to be recontacted varied based on certainty of results. For certain results, WTP was highest for being recontacted by a doctor with updates ($1075, 95% CI: $845, $1305) and for contacting a doctor to request updates ($1038, 95% CI: $820, $1256). For VUS results, WTP was highest for an online database ($1735, 95% CI: $1224, $2247) and for contacting a doctor ($1705, 95% CI: $1102, $2307). Qualitative data revealed that preferences for provider-mediated recontact were influenced by trust in healthcare providers. Preferences for a database were influenced by lack of trust in providers and desire for control. Patients and public participants support an online database (e.g. patient portal) to recontact for VUS, improving feasibility, and provider-mediated recontact for certain results, consistent with usual care.

Physical aggression (PA) is important to regulate as early as the preschool years in order to ensure healthy development of children. This study aims to determine the prevalence and characteristics of PA in children of immigrant and non-immigrant mothers. Secondary data analysis was conducted using the nationwide 2010 Survey for Young Canadians, limited to children 4-9 years of age. Bivariate and multivariable logistic regression was performed, with the outcome, PA, and covariates including maternal, child, household and neighbourhood characteristics. Twenty percent of children of non-immigrant mothers and 16% of children of immigrant mothers reported PA. The only common characteristic of PA between children of non-immigrant (Adj OR 1.44, 95% CI 1.09-1.89) and immigrant mothers (Adj OR 2.08, 95% CI 1.07-4.03) was viewing violent movies/shows. The characteristics of PA differ between children of immigrant versus non-immigrant mothers therefore healthcare providers, policy makers, and researchers should be mindful to address PA in these two groups separately, and find ways to tailor current recommended coping strategies and teach children alternative ways to solve problems based on their needs.

Aims Advances in arthroscopic techniques for rotator cuff repair have made the mini-open approach less popular. However, the mini-open approach remains an important technique for repair for many surgeons. The aims of this study were to compare the integrity of the repair, the function of the shoulder and satisfaction post-operatively using these two techniques in patients aged > 50 years. Patients and Methods We identified 22 patients treated with mini-open and 128 patients treated with arthroscopic rotator cuff repair of July 2007 and June 2011. The mean follow-up was two years (1 to 5). Outcome was assessed using the American Shoulder and Elbow Surgeons (ASES) and Simple Shoulder Test (SST) scores, and satisfaction. The integrity of the repair was assessed using ultrasonography. A power analysis ensured sufficient enrolment. Results There was no statistically significant difference between the age, function, satisfaction, or pain scores (p > 0.05) of the two groups. The integrity of the repair and the mean SST scores were significantly better in the mini-open group (91% of mini-open repairs were intact versus 60% of arthroscopic repairs, p = 0.023; mean SST score 10.9 (standard deviation (sd) 1.3) in the mini-open group; 8.9 (sd 3.5) in arthroscopic group; p = 0.003). The ASES scores were also higher in the mini-open group (mean ASES score 91.0 (sd 10.5) in mini-open group; mean 82.70 (sd 19.8) in the arthroscopic group; p = 0.048). Conclusion The integrity of the repair and function of the shoulder were better after a mini-open repair than after arthroscopic repair of a rotator cuff tear in these patients. The functional difference did not translate into a difference in satisfaction. Mini-open rotator cuff repair remains a useful technique despite advances in arthroscopy. Cite this article: Bone Joint J 2017;99-B:245–9.

Noninvasive fat reduction is claimed by many device manufacturers, but proof of efficacy has been difficult to establish. This prospective study was designed to measure the reduction of fat thickness and actual volume reduction in 20 female patients treated with an external radiofrequency (RF) device. This device combines RF heat, suction coupled vacuum, and oscillating electrical pulses that induce adipocyte death over time. Patients underwent pre- and post-treatment and intercurrent measurements of weight, body mass index, ultrasonic transcutaneous fat thickness, and 2D and 3D Vectra photography with independent calculation of circumferential and volumetric change. Mean transcutaneous ultrasound thickness at reproducible points was 2.78 cm; at 1-month post-treatment, the mean fat thickness was 1.71 cm. At 3-month post-treatment, the mean fat thickness reduction was 39.6%. Vectra circumference measurements were taken at 10-mm intervals, with postural and breathing cycle control. Independent analysis of serial measurements from + 60 to - 70 mm showed mean abdominal circumference measurement of 2.3 cm. Mean abdominal volume loss was 202.4 and 428.5 cc at 1- and 3-month post-treatment, respectively. Scanning electron microscopy confirmed that permanent cell destruction was caused by irreversible electroporation. Pyroptosis appears to be the mechanism of action.

To date, there have been no objective measurements of subcutaneous volume loss following treatments with a noninvasive radiofrequency (RF)-based device. Twenty female patients were treated with a suction-coupled bipolar RF device using external RF energy combined with pulsed electromagnetic RF energy for subcutaneous fat reduction. Parameters followed included weight, Vectra measurements of abdominal circumference and torso volume, and high-definition ultrasound measurements of fat thickness. Measurements were taken before treatment and three times following treatment. Analysis of the measured parameters showed that mean circumference reduction of 2.30 cm was noted at three months post-treatment. Independent volumetric analysis showed a mean subcutaneous volume reduction of 428 cc three months following RF treatment. High-resolution ultrasound fat thickness was reduced by a mean of 39.6% three months following the final BodyFX treatment. Independent and paired-sample t-tests showed a p value of < 0.05. Repeated measures of analysis of covariance (ANCOVA) adjusted for differences in age, as well as height and weight (proxy for body mass index) to minimize individual differences and control for extraneous variables that may affect the pre- and post-treatment results were analyzed. No confounding variables were found. All analyses were conducted using IBM SPSS 21.0.

Objective To describe obstetrical and neonatal outcomes including neonatal abstinence syndrome (NAS) in a Canadian cohort of methadone-maintained pregnant women. Methods We conducted a retrospective chart review at three integrated care programs in Vancouver, Toronto, and Montreal. Pregnant women on methadone maintenance treatment (MMT) who attended for care between 1997 and 2009 were included in this multisite study. Maternal and neonatal outcomes in each of the three contributing centres were compared. Results A total of 94 pregnant methadone-maintained women were included in the final analysis: 36 from Toronto, 36 from Vancouver, and 22 from Montreal. Maternal demographics showed inter-site differences in ethnicity and marital status. Obstetrical complications were not frequent; the most frequent was antenatal hemorrhage, which occurred in 14% of the total cohort. The incidence of premature labour was significantly higher in Vancouver and Montreal than in Toronto. The mean gestational age at delivery for the entire cohort was 38weeks; mean birth weight was 2856 grams. The average length of hospital stay for babies with NAS was 19days, with 27% of neonates requiring pharmacological treatment for NAS. Approximately 60% of neonates were discharged from hospital to the care of their mother. Conclusion Integrated care programs resulted in satisfactory obstetrical and neonatal outcomes for pregnant women on MMT. Policies promoting maternal–newborn contact, rooming-in, and breastfeeding may help to decrease the severity of NAS and the need for pharmacological treatment of NAS. We strongly recommend the development of similar programs across Canada to address gaps in services.

Background Positive-interaction parenting early in childhood is encouraged due to its association with behavioural development later in life. The objective of this study was to examine if the level of positive-interaction parenting style differs among teen, optimal age, and advanced age mothers in Canada, and to identify the characteristics associated with positive-interaction parenting style separately for each age group. Methods This was a cross-sectional secondary analysis of the National Longitudinal Survey of Children and Youth. First-time mothers with children 0–23 months were grouped into: teen (15–19 years, N = 53,409), optimal age (20–34 years, N = 790,960), and advanced age (35 years and older, N = 106,536). The outcome was positive-interaction parenting style (Parenting Practices Scale); maternal socio-demographics, health, social, and child characteristics were considered for backward stepwise multiple linear regression modeling, stratified for each of the age groups. Results Teen, optimal age, and advanced age mothers reported similar levels of positive- interaction parenting style. Covariates differed across the three age groups. Among optimal age mothers, being an ever-landed immigrant, childcare use, and being devoted to religion were found to decrease positive-interaction parenting style, whereas, higher education was found to increase positive-interaction parenting style. Teen mothers were not found to have any characteristics uniquely associated with positive-interaction parenting. Among advanced age mothers, social support was uniquely associated with an increase in positive-interaction parenting. Very good/excellent health was found to be positively associated with parenting in teens but negatively associated with parenting in advanced age mothers. Conclusion Characteristics associated with positive-interaction parenting varied among the three age groups. Findings may have public health implications through information dissemination to first-time mothers, clinicians, researchers, and public health facilities.

Background A negative birth experience has been shown to have a significant impact on the well-being and future choices of mothers. The objective of this study was to assess the prevalence of, and identify the risk factors associated with a negative birth experience for women in Canada. Methods The study was based on secondary data analysis of the Maternity Experiences Survey (MES), a Canadian population database administered to 6,421 Canadian women in 2006. The examined outcome - negative birth experience – was derived from mothers’ self-report of overall labour and birth experience. Independent variables were maternal demographics, health characteristics, pregnancy-related characteristics, and birth characteristics. Multivariable logistic regression analysis was performed to determine the significant predictors of negative birth experience. Adjusted Odds Ratios (AOR) and 95 % Confidence Intervals (CI) are reported. Results Negative birth experience was reported among 9.3 % of women. The main significant predictors of a negative birth experience included older age (AOR 2.29, 95 % CI, 1.03–5.07), violence experienced in the past two years (AOR, 1.62, 95 % CI, 1.21–2.18), poor self-perceived health (adjusted OR, 1.95, 95 % CI, 1.36–2.80), prenatal classes attended (adjusted OR, 1.36, 95 % CI, 1.06–1.76), unintended pregnancy (adjusted OR, 1.30, 95 % CI, 1.03–1.63), caesarean birth (AOR, 1.65, 95 % CI, 1.32–2.06), and neonate admission to intensive care (AOR, 1.40, 95 % CI, 1.08–1.82). Conclusion Significant predictors of a negative labour and birth experience were identified through this study, a first in the Canadian context. These findings suggest future research directions and provide a basis for the design and evaluation of maternal health policy and prevention programs.

Histidine decarboxylase (HDC) catalyzes the formation of histamine from histidine. Histamine has various effects in physiological and pathological reactions, such as inflammation, cell growth, and neuro-transmission. We investigated the role of hypoxia-inducible factor (HIF)-1 on hypoxia-induced HDC expression in human mast cell line, HMC-1 cells and mouse bone marrow-derived mast cells (BMMCs). Hypoxia significantly increased histamine production. HDC expression and activity were induced by hypoxia. Additionally, when cells were transfected with a native form of HIF-1alpha, hypoxia could induce higher HDC expression than in the nontransfected cell. HIF-1 binding activity for HDC 5' flanking region (HFR) was similar to that for the hypoxia-responsive element. Using HDC promoter deletion analysis, we also demonstrated that HFR was regulated by HIF-1 activation. In addition, depletion of HIF-1alpha prevents hypoxic induction of HDC in BMMCs. In conclusion, these results demonstrate that hypoxia induces HDC expression by transcriptional mechanisms dependent upon HIF-1.

Background Unintended pregnancies (mistimed or unwanted during the time of conception) can result in adverse outcomes both to the mother and to her newborn. Further research on identifying the characteristics of unintended pregnant women who are at risk is warranted. The present study aims to examine the prevalence and predictors of unintended pregnancy among Canadian women. Methods The analysis was based on the 2006 Maternity Experiences Survey targeting women who were at least 15 years of age and who had a singleton live birth, between February 15, 2006 to May 15, 2006 in the Canadian provinces and November 1, 2005 to February 1, 2006 for women in the Canadian territories. The primary outcome was the mother’s pregnancy intention, where unintended pregnancy was defined as women who wanted to become pregnant later or not at all. Sociodemographic, maternal and pregnancy related variables were considered for a multivariable logistic regression. Results Adjusted Odds Ratios (OR) and 95 % Confidence Intervals (95 % CI) were reported. Overall, the prevalence of unintended pregnancy among Canadian women was 27 %. The odds of experiencing an unintended pregnancy were statistically significantly increased if the mother was: under 20 years of age, immigrated to Canada, had an equivalent of a high school education or less, no partner, experienced violence or abuse and had 1 or more previous pregnancies. Additionally, mothers who reported smoking, drinking alcohol and using drugs prior to becoming pregnant, were all associated with an increased likelihood of experiencing an unintended pregnancy. Conclusion The study findings constitute the basis for future research into these associations to aid in developing effective policy changes and interventions to minimize the odds of experiencing an unintended pregnancy and its associated consequences.

Background There is limited research focusing on adolescent women who intended to become pregnant, as majority of research examines unintended adolescent pregnancies. The objective was to examine the prevalence and characteristics of Canadian adolescent women who intended to become pregnant. Methods The analysis was based on the national 2006 Maternity Experiences Survey consisting of women who had a singleton live birth. The sample was restricted to adolescent women between 15 to 19 years of age. The main outcome of this study was the adolescent woman’s pregnancy intention. A variety of sociodemographic, maternal, and pregnancy related factors were examined using a multivariable logistic regression. Adjusted odds ratios (OR) and 95 % confidence intervals (CI) were reported for all variables. Results The sample size was 290, weighted to represent 2224 adolescent women. Based on the adjusted model, the odds of experiencing an intended pregnancy were increased if the adolescent woman was between 18–19 years old (OR 2.62, 95 % CI 1.05, 6.57), had a partner (OR 2.37, 95 % CI 1.12, 4.99), experienced no violence/abuse (OR 3.08, 95 % CI 1.38, 6.86), and consumed no alcohol before pregnancy (OR 3.17, 95 % CI 1.56, 6.45). Additionally, adolescent women who reported drug use prior to pregnancy were more likely to have an intended pregnancy (OR 0.39, 95 % CI 0.16, 0.95). Conclusion The findings from this study can be used as the basis for future research to investigate the characteristics and needs represented by this group of adolescents and to aid in the development of effective policies and programs.

The positive effects of physical activity on the well-being of older adults have been well documented. Tai chi is a suitable form of physical activity, with known physical and psychological benefits for older adults.The objective of the current study was to compare the effects of participation in a 16-wk tai chi program on the functional fitness of older adults with and without previous tai chi experience.The research team designed a prospective cohort study. Participants who had practiced tai chi previously for ≥1 y at baseline were classified as experienced; all others were considered inexperienced.The study took place at 2 community centers in 2 locations in the Greater Toronto area of Ontario, Canada.Participants were residents of the 2 communities.Participants were instructed to attend two 1-h sessions of Yang-style tai chi per wk.Data on functional fitness- strength, endurance, speed, and flexibility-were collected at baseline and after completion of the tai chi program.Of the 143 participants who completed the study, 20.5% were classified as experienced. Experienced participants had significantly higher ratings on functional fitness tests at baseline compared with the inexperienced group. At the end of the study, inexperienced participants had experienced significant improvements in all measures of functional fitness, although experienced participants had shown significant improvements only in measures of endurance and speed.Tai chi appears to be an optimal mode of physical activity for older adults regardless of previous experience with tai chi.

A pocket guide on management of substance use during pregnancy was developed by a group of Canadian care providers. One hundred and fifteen family medicine residents in 6 Canadian teaching sites were randomized to receive either the pocket guide or a paper summary on similar clinical topics, based on UpToDate, a comprehensive Web-based resource. At baseline, both groups completed a survey containing questions on beliefs, attitudes, experience, and training on pregnancy and substance use. Participants then answered 28 multiple choice questions about substance use in pregnancy, using either the pocket guide or UpToDate. Finally participants were asked to rate ease of use for the 2 resources. The results showed that the pocket guide group had higher knowledge scores than the UpToDate group overall and at each study site (61.27% vs. 42.86%, P < .001). The residents found the pocket guide easier to use than UpToDate (mean = 2.73 vs. 4.36, P < .001), and were more likely to want to use it again (96% for pocket card, 78% for UpToDate, P = .005). It is concluded that the pocket guide is a practical source of clinical information at point of care, particularly for “orphan” subjects such as substance use in pregnancy.

The relationship between cerebrovascular disease and an insertion/deletion (I/D) polymorphism in the angiotensin-converting enzyme (ACE) gene is still being debated. The frequency of the DD genotype of the ACE gene was significantly higher in subjects with than those without cerebral infarction in Japan. The aim of the present study was to assess the relationship between ACE gene polymorphism and the development of cerebral infarction in a population from Korea. We examined its possible role as a risk factor in patients with cerebral infarction. The association between ACE gene polymorphism and cerebral infarction was examined in 106 patients with cerebral infarction and 498 controls without cerebral infarction. Frequencies of the genotypes and alleles of the ACE gene were investigated. The ACE genotype was analyzed by the polymerase chain reaction (PCR). The frequency of D allele was 37.7% in patients and 39.1% in controls (chi2 = 0.128, p = 0.720). The frequencies of the genotypes of the ACE gene were II: 39.6%, ID: 45.3%, and DD: 15.1% in patients, and II: 37.1%, ID: 47.6%, and DD: 15.3% in controls (chi2 = 0.127, p = 0.721). There was no significant difference in the frequency of the DD genotype of the ACE gene, and we did not find any association between ACE polymorphism and cerebral infarction. These results indicate that ACE polymorphism is not a risk factor for the development of cerebral infarction in a Korean population.

Women seeking consultation for the surgical relief of symptoms associated with breast hypertrophy have been the focus of many studies. In contrast, little is known about those women with breast hypertrophy who do not seek symptomatic relief. The purpose of this study was to describe the health burden of breast hypertrophy by using a set of validated questionnaires and to compare women with breast hypertrophy who seek surgical treatment with those who do not. In addition, this latter group was compared with a group of control women without breast hypertrophy. Women seeking consultation for surgery were recruited from 14 plastic-surgery practices. Control subjects were recruited by advertisements in primary-care offices and newspapers. Women were asked to complete a self-report questionnaire that included the European Quality of Life (EuroQol) questionnaire, McGill Pain Questionnaire, Multidimensional Body Self Relations Questionnaire (MBSRQ), the Short Form-36 (SF-36) questionnaire, and questions regarding breast-related symptoms, comorbidities, and bra size. Descriptive statistics were compiled for three groups of women: (1) hypertrophy patients seeking surgical care, (2) hypertrophy control subjects (those whose reported bra-cup size was a D or larger), and (3) normal control subjects (those whose reported bra-cup size was an A, B, or C). The multiple linear regression method was used to compare the health burdens across groups while adjusting for other variables. Two hundred ninety-one women seeking surgical care and 195 control subjects were enrolled in the study. The 184 control subjects with bra-cup information available were further separated into 88 hypertrophy control subjects and 96 normal control subjects. In the control group, bra-cup size was correlated with health-burden measures, whereas in the surgical candidates, it was not. When scores were compared across the three groups, significant differences were found in all health-burden measures. The surgical candidates scored more poorly on the EuroQol utility, McGill pain rating index, MBSRQ appearance evaluation, physical component scale of the SF-36, and on breast symptoms than did the two control groups. In addition, the hypertrophy control subjects scored more poorly than the normal control subjects. With multiple linear regression analysis incorporating important potential confounders, the poorer scores in the surgical candidates remained statistically significant. It was concluded that breast hypertrophy in those seeking surgical care and those not seeking surgery has a significant impact on women's quality of life as measured by validated and widely used self-report instruments including the EuroQol, MBSRQ, McGill Pain Questionnaire, and the SF-36. Likewise, a new assessment instrument for breast-related symptoms also demonstrated greater symptomatology in women with breast hypertrophy.

Prodigiosin (PDG) was previously reported to be a T cell-specific immunosuppressant. Here we describe the mechanism of action of PDG in T cells and the effect of PDG on autoimmune diseases. PDG selectively suppresses concanavalin A (Con A)-induced T cell proliferation, but has little effect on lipopolysaccharide-induced proliferation of B cells and nitric oxide production of macrophages. Although PDG does not block interleukin (IL)-2 production, it efficiently inhibits interleukin-2 receptor alpha-chain (IL-2Ralpha) expression, and this results in a disruption of the IL-2/IL-2R signaling pathway, on which a great part of the regulation of T cell activation depends. PDG blocks T cell differentiation into effector helper T cells secreting interferon-gamma and IL-4 as well as into effector cytotoxic T lymphocytes expressing perforin, which is at least in part resulting from inhibition of the IL-2/IL-2R signaling. PDG indirectly blocks signal transducer and activator of transcription activation by inhibiting cytokine signalings in Con A-activated T cells, although it does not inhibit the activation of nuclear factor-kappaB, nuclear factor of activated T cells, and activator protein-1. As direct evidence of immunosuppression in vivo, we show that PDG markedly reduced blood glucose levels and cellular infiltration into the pancreatic islets in nonobese diabetic mice, and that it also delays the onset of collagen-induced arthritis in DBA/1 mice. In conclusion, our results demonstrate that PDG has a unique mode of action, namely, that it blocks T cell activation by inhibiting primarily IL-2Ralpha expression in the IL-2/IL-2R signaling, and show that this compound represents a promising immunosuppressant candidate for the treatment of autoimmune diseases.

Host immune response is known to contribute to the progression of periodontitis, and alveolar bone destruction in periodontitis is associated with enhanced osteoclast activity. Therefore, we evaluated the roles of activated lymphocyte subsets in osteoclastogenesis. Osteoclast precursors were co-cultured with activated lymphocytes (B, CD4(+) T, CD8(+) T) in the presence of either macrophage colony-stimulating factor (M-CSF) alone or M-CSF plus soluble receptor activator of NF-kappaB ligand (sRANKL), and subsequent differentiation into active osteoclasts was evaluated by a resorption assay. The activated B and CD4(+) cells, but not CD8(+) T cells, induced osteoclast differentiation in the presence of M-CSF alone. In the presence of M-CSF and sRANKL, B cells induced the formation of small but highly active osteoclasts and increased resorption, while CD8(+) T cells profoundly suppressed osteoclastogenesis. Co-culture using an insert well or supernatant suggested that both B and CD8(+) T cells acted on osteoclasts mostly via soluble proteins. Activated B cells expressed many osteoclastogenic factors including RANKL, TNF-alpha, IL-6, MIP-1alpha, and MCP-3. CD8(+) T cells expressed a substantial amount of osteoprotegerin (OPG) along with RANKL. However, blocking antibody to OPG did not reverse the suppression by CD8(+) T cells, suggesting that other factor(s) are involved. Taken together, activated B cells promoted osteoclastogenesis, while CD8(+) T cells inhibited the osteoclast formation via direct interaction. The results imply the importance of lymphocyte subpopulations in the development of periodontitis.

At arterial phase gadolinium-enhanced magnetic resonance (MR) angiography, artifactual stenosis of the subclavian artery is sometimes seen adjacent to the subclavian vein on the side of the contrast material injection. Experiments in phantoms and in 19 patients showed increased artifact with longer echo time and higher concentration of injected contrast material. An effective method to substantially decrease this susceptibility artifact was threefold dilution of gadopentetate dimeglumine and use of a short echo time (1 msec).

The mi locus encodes a member of the basic-helix-loop-helix-leucine zipper (bHLH-Zip) protein family of transcription factors (hereafter called MITF). We reported that expression of the mouse mast cell protease 5 (MMCP-5) and MMCP-6 genes were deficient in cultured mast cells (CMC) derived from mutant mice of mi/mi genotype. Despite the reduced expression of both MMCP-5 and MMCP-6, their regulation mechanisms were different. Because MMCP-5 is a chymase and MMCP-6 a tryptase, there was a possibility that the difference in regulation mechanisms was associated with their different characteristics as proteases. We compared the regulation mechanisms of another chymase, MMCP-4, with those of MMCP-5 and MMCP-6. The expression of the MMCP-4 gene was also deficient in mi/mi CMC. The overexpression of the normal (+) MITF but not of mi-MITF normalized the poor expression of the MMCP-4 gene in mi/mi CMC, indicating the involvement of +-MITF in transactivation of the MMCP-4 gene. Although MMCP-4 is chymase as MMCP-5, the regulation of MMCP-4 expression was more similar to MMCP-6 than to MMCP-5. We also showed the deficient expression of granzyme B and cathepsin G genes in mi/mi CMC. Genes encoding granzyme B, cathepsin G, MMCP-4, and MMCP-5 are located on chromosome 14. Because all these genes showed deficient expression in mi/mi CMC, there is a possibility that MITF might regulate the expression of these genes through a locus control region.

We present the clinical results of laser assisted in situ keratomileusis (LASIK) to correct myopia of more than -10.00 diopters (D).Eighteen eyes are included in this study. Pre-operative spherical equivalent was -16.40 D, range from -10.50 to -21.50 D. Hinge corneal cap techniques were used with automated microkeratome (Steinway, USA). The thickness of the flap was 130 microns. The stromal bed was ablated with the OmniMed II excimer laser, using the standard MKM program (Summit Technology, Inc., Waltham, MA). The ablation zone was between 4.2 and 5.0 mm.At 6 months postoperatively, the mean spherical equivalent was +0.14 D with a range of +3.50 to -2.00 D. A result within 2.00 D of the desired correction was achieved in 93% of eyes, while a result within 1.00 D was achieved in 47%. Uncorrected visual acuity was improved in all cases. One eye lost greater than two lines of pre-operative best corrected vision due to macular hemorrhage.These data show that the LASIK procedure appears to be effective for correcting high myopia.

The ability of putative Ca(2+)-ATPase inhibitor of endoplasmic reticulum (ER), thapsigargin (TG), to induce nitric oxide (NO) synthesis in murine peritoneal macrophages was examined. TG alone had small effect on NO synthesis, whereas TG in combination with LPS markedly increased NO synthesis in a dose dependent manner. This increase in NO synthesis was reflected as increased amount of inducible NO synthase (iNOS) mRNA by Northern blotting. In addition, the ability of TG on NO synthesis could be mimicked by another chemically unrelated inhibitor of Ca(2+)-ATPase, 2,5-DI-(t-butyl)-1, 4-benzohydroquinone (tBuBHQ). Adding EGTA, a calcium chelator, to the incubation medium significantly reduced the ability of macrophages to induce NO synthesis in response to the optimal stimulation of TG or TG plus LPS. These results therefore demonstrate that intracellular Ca2+ pool depletion is linked to the induction of NO synthesis in murine peritoneal macrophages and further suggest that it is also related with interferon-gamma (IFN-gamma)-induced signaling.

Background Postpartum depression (PPD) is a mood disorder that affects 10–20 percent of women, and can begin any time during first year after delivery lasting for months. Social support may decrease risk of depression during pregnancy for women. However, literature shows that the amount of social support received during and after pregnancy is different for teen mothers and adult mothers. This study examined the effects of social support received during and after pregnancy on PPD among Canadian women and identified if the relationship was different for teen mothers compared to adult mothers. Methods The study was based on secondary analysis of the Maternity Experiences Survey. A total of 6,421 women with singleton live births, aged 15 years and older were analyzed. Teen mothers were identified as 15–19 years old and adult mothers were identified as 20 years and older. The main outcome of the study was PPD, which was evaluated using the Edinburg Postnatal Depression Scale. The main independent variable was social support received during pregnancy and after birth. Logistic regression was computed to assess the relationship between social support and PPD after adjusting for confounding variables and age as an interaction term. Adjusted Odds Ratios and 95% Confidence Intervals were reported. Results PPD was experienced by 14.0% among teen mothers and 7.2% among adult mothers (p

Background Tai Chi practice has some fitness, wellness, and general cognitive effects in older adults. However, benefits of Tai Chi on specific mental-attentional executive processes have not been investigated previously. We studied older Canadian adults of Chinese and non-Chinese origin and from low socioeconomic areas. Methods Sixty-four adults (51–87 years old) took part in a 16-week Tai Chi program. There were two groups: Chinese-background (n = 35) and Non-Chinese-background (n = 29). They received four mental-attention executive tasks before and after the 16-week period. These tasks measured visuospatial reasoning, mental-attentional activation (working memory), attentional inhibition, and balance between these attention factors (field-dependence-independence). Results Chinese participants showed significant gain on Figural Intersections Task (mental-attentional capacity), Antisaccade (attentional inhibition), and Matrix Reasoning (fluid intelligence measure). Both groups evidenced gain on the Water Level Task (attentional balance). Conclusions These gains suggest that Tai Chi can improve mental-attentional vigilance and executive control, when practitioners are sufficiently motivated to pursue this practice, and apply themselves (as our Chinese participants seem to have done). We found that Tai Chi enhanced mental attentional executives in the Chinese sample. The largely negative results with Non-Chinese participants might be explained by less strong motivation and by the relatively short Tai Chi practice period, which contrasts with the prior familiarity with Tai Chi of the Chinese participants.