Temporal trends in thyroid-stimulating hormone and live birth rate in subclinical hypothyroid patients in a recurrent pregnancy loss population.

OBJECTIVES: The purpose of this study was to explore if thyroperoxidase antibody positivity impacts thyroid stimulating hormone levels during pregnancies following the index visit and how live birth rate is impacted when treated subclinical hypothyroidism is treated with levothyroxine or not. STUDY DESIGN: A retrospective chart review of 1443 recurrent pregnancy loss patients from BC Women's Hospital recurrent pregnancy loss clinic was conducted. Thyroid stimulating hormone in pregnancies after the index visit across thyroperoxidase antibody status was analyzed using mixed-effects linear regression. Live birth rate in patients with subclinical hypothyroidism (thyroid stimulating hormone 2.5-10 mIU/L) with levothyroxine treatment was compared to those without relative to euthyroid patients using logistic regression. RESULTS AND CONCLUSIONS: There was no significant difference in patient demographics including age, body mass index, or number of previous live births or pregnancy losses between groups. The distribution of recurrent pregnancy loss causes between groups revealed no difference in proportion of patients with anti-phospholipid antibody syndrome, hereditary thrombophilia, hyperprolactinemia, or anatomic causes. There was no significant change in thyroid stimulating hormone across thyroperoxidase antibody or treatment status (p = 0.24) for up to four subsequent pregnancies. An increased live birth rate in subclinical hypothyroidism when treated with levothyroxine relative to untreated (OR = 2.25, p < 0.001) was seen. Thyroid stimulating hormone values do not change over time following the index visit for up to 4 subsequent pregnancies irrespective of the thyroxperoxidase antibody status. An increase in live birth rate was found in patients with borderline subclinical hypothyroidism when treated with levothyroxine.

Risk Prediction for Delayed Allograft Function: Analysis of the Deterioration of Kidney Allograft Function (DeKAF) Study Data.

BACKGROUND: Delayed graft function (DGF) of a kidney transplant results in increased cost and complexity of management. For clinical care or a DGF trial, it would be ideal to accurately predict individual DGF risk and provide preemptive treatment. A calculator developed by Irish et al has been useful for predicting population but not individual risk. METHODS: We analyzed the Irish calculator (IC) in the DeKAF prospective cohort (incidence of DGF = 20.4%) and investigated potential improvements. RESULTS: We found that the predictive performance of the calculator in those meeting Irish inclusion criteria was comparable with that reported by Irish et al. For cohorts excluded by Irish: (a) in pump-perfused kidneys, the IC overestimated DGF risk; (b) in simultaneous pancreas kidney transplants, the DGF risk was exceptionally low. For all 3 cohorts, there was considerable overlap in IC scores between those with and those without DGF. Using a modified definition of DGF-excluding those with single dialysis in the first 24 h posttransplant-we found that the calculator had similar performance as with the traditional DGF definition. Studying whether DGF prediction could be improved, we found that recipient cardiovascular disease was strongly associated with DGF even after accounting for IC-predicted risk. CONCLUSIONS: The IC can be a useful population guide for predicting DGF in the population for which it was intended but has limited scope in expanded populations (SPK, pump) and for individual risk prediction. DGF risk prediction can be improved by inclusion of recipient cardiovascular disease.

Pharmacist dispensing of the abortion pill in Canada: Diffusion of Innovation meets integrated knowledge translation.

BACKGROUND: Since Canadian drug regulatory approval of mifepristone for medical abortion in 2015 and its market availability in January 2017, the role of pharmacists in abortion provision has changed rapidly. We sought to identify the factors that influenced the initiation and provision of medical abortion from the perspectives of Canadian pharmacists, bridging two frameworks - Diffusion of Innovation in Health Service Organizations and integrated knowledge translation. METHODS: We conducted one-on-one semi-structured interviews with pharmacists residing in Canada who intended to stock and dispense mifepristone within the first year of availability. Our data collection, analysis, and interpretation were guided by reflexive thematic analysis and supported by an integrated knowledge translation partnership with pharmacy stakeholders. RESULTS: We completed interviews with 24 participants from across Canada: 33% had stocked and 21% had dispensed mifepristone. We found that pharmacists were willing and able to integrate medical abortion care into their practice and that those who had initiated practice were satisfied with their dispensing experience. Our analysis indicated that several key Diffusion of Innovation constructs impacted the uptake of mifepristone, including: innovation (relative advantage, complexity and compatibility, technical support), system readiness (innovation-system fit, dedicated time, resources), diffusion and dissemination (expert opinion, boundary spanners, champions, social networks, peer opinions), implementation (external collaboration), and linkage. Participants' experiences suggest that integrated knowledge translation facilitated evidence-based changes to mifepristone dispensing restrictions, and communication of those changes to front line pharmacists. CONCLUSIONS: We illustrate how Diffusion of Innovation and integrated knowledge translation may work together as complimentary frameworks for implementation science research. Unlike in the USA, UK, and other highly regulated settings globally, pharmacists in Canada are permitted to dispense mifepristone for medical abortion. We contribute to literature that shows that mifepristone dispensed outside of hospitals, clinics, and medical offices is safe and acceptable to both patients and prescribers. This finding is of particular importance to the current COVID-19 pandemic response and calls for continued and equitable access to abortion care in primary practice.

Perspectives Among Canadian Physicians on Factors Influencing Implementation of Mifepristone Medical Abortion: A National Qualitative Study.

PURPOSE: Access to family planning health services in Canada has been historically inadequate and inequitable. A potential solution appeared when Health Canada approved mifepristone, the gold standard for medical abortion, in July 2015. We sought to investigate the factors that influence successful initiation and ongoing provision of medical abortion services among Canadian health professionals and how these factors relate to abortion policies, systems, and service access throughout Canada. METHODS: We conducted 1-on-1 semistructured interviews with a national sample of abortion-providing and nonproviding physicians and health system stakeholders in Canadian health care settings. Our data collection, thematic analysis, and interpretation were guided by Diffusion of Innovation theory. RESULTS: We conducted interviews with 90 participants including rural practitioners and those with no previous abortion experience. In the course of our study, Health Canada removed mifepristone restrictions. Our results suggest that Health Canada's initial restrictions discouraged physicians from providing mifepristone and were inconsistent with provincial licensing standards, thereby limiting patient access. Once deregulated, remaining factors were primarily related to local and regional implementation processes. Participants held strong perceptions that mifepristone was the new standard of care for medical abortion in Canada and within the scope of primary care practice. CONCLUSION: Health Canada's removal of mifepristone restrictions facilitated the implementation of abortion care in the primary care setting. Our results are unique because Canada is the first country to facilitate provision of medical abortion in primary care via evidence-based deregulation of mifepristone.

Prevalence of thyroid autoimmunity and effect of levothyroxine treatment in a cohort of 1064 patients with recurrent pregnancy loss.

RESEARCH QUESTION: Does initiating levothyroxine treatment based on thyroid-stimulating hormone (TSH) >2.5 mIU/l or thyroid autoimmunity improve pregnancy continuation rates in recurrent pregnancy loss (RPL) patients? DESIGN: A retrospective cohort study of 1064 RPL patients, in which subjects were classified as either euthyroid (TSH 0.1 to ≤2.5 mIU/l), borderline-subclinical hypothyroid (borderline-SCH, TSH 2.5 to ≤4 mIU/l) or subclinical hypothyroid (SCH, TSH 4 to ≤10 mIU/l). For subjects with ≥2 pregnancy losses and a subsequent pregnancy with known outcome, a comparison was done of the pregnancy continuation rate past 10 weeks of treated and untreated borderline-SCH (n = 98) and untreated euthyroid (n = 279) subjects, and between subjects with positive (n = 18) and negative (n = 206) thyroid peroxidase (TPOAb tests) within the borderline-SCH and euthyroid groups. RESULTS: 72.7% were euthyroid (721/992), 19.4% (192/992) were borderline-SCH, and 5.4% (54/992) were subclinically hypothyroid (SCH). Of 401 women with a subsequent pregnancy of known outcome at 10 gestational weeks, 21% received treatment with levothyroxine. 57.7% of subjects had a TPOAb test, which was positive in 9.25% (37/400) in euthyroid, 16.5% (22/133) in borderline-SCH subjects and 35.3% (12/34) in SCH subjects. Treatment did not improve pregnancy continuation rates in borderline-SCH subjects (P = 0.392). There was no difference in pregnancy outcomes based on TPOAb status and treatment for borderline-SCH subjects (P = 0.4214), or based on TPOAb status for euthyroid subjects (P = 0.2668). CONCLUSIONS: Treatment of hypothyroidism in pregnancy should be initiated based on a TSH >4 mIU/l. Treatment initiation based on thyroid autoimmunity or a TSH >2.5 mIU/l may result in overtreatment.

Late Graft Loss After Kidney Transplantation: Is "Death With Function" Really Death With a Functioning Allograft?

BACKGROUND: About half of late kidney allograft losses are attributed to death with function (DWF), a poorly characterized outcome. An ongoing question is whether DWF is a consequence of chronic allograft dysfunction. Using the prospective Long-term Deterioration of Kidney Allograft Function study database, we sought to better define the impact, phenotype, and clinical course of DWF in the current era. METHODS: Three thousand five hundred eighty-seven kidney recipients with functional grafts at 90 days post-transplant were followed prospectively for a median of 5.2 years. RESULTS: Characteristics at transplantation in those with DWF (N = 350, 9.8%) differed from those who otherwise lost their grafts (death-censored graft failure [DC-GF], N = 295, 8.2%) or maintained function (N = 2942, 82.0%); DWF patients were older, sicker, and had been on dialysis longer, with more preexisting cardiovascular disease, whereas DC-GF patients experienced more early rejection, more acute rejection after 90 days, and a clinically significant decrease in kidney function before graft failure. In contrast, the clinical course after transplantation in DWF patients did not differ before death from those who maintained function throughout. CONCLUSIONS: DWF and DC-GF in kidney transplant recipients represent differing clinical phenotypes occurring in distinct patient populations. Reducing the impact of DWF requires better definition of causes and clinical course and then trials of therapies to improve outcomes. Composite endpoints in clinical trials that group DWF and DC-GF together may obscure important clinical findings.

A Group Randomized Intervention Trial Increases Participation in the School Breakfast Program in 16 Rural High Schools in Minnesota.

BACKGROUND: Breakfast consumption is associated with better diet quality and healthier weights, yet many adolescents miss breakfast. Nationally, 17.1% of students participate in the School Breakfast Program (SBP). Only 10% of high school students participate. OBJECTIVE: Our aim was to evaluate an environmental intervention to increase SBP participation in high schools. DESIGN: A group randomized trial was carried out from 2012 to 2015. PARTICIPANTS/SETTING: Ninth- and 10th-grade students enrolled in 16 rural schools in Minnesota (median 387 students) were randomized to intervention or control condition. INTERVENTION: A school-based intervention that included two key components was implemented over a 12-month period. One component focused on increasing SBP participation by increasing student access to school breakfast through changes in school breakfast service practices (eg, serving breakfast from a grab-n-go cart in the atrium; expanding breakfast service times). The other component focused on promoting school breakfast through student-directed marketing campaigns. MAIN OUTCOME MEASURE: Change in school-level participation in the SBP was assessed between baseline (among ninth and tenth graders) and follow-up (among tenth and eleventh graders). School meal and attendance records were used to assess change in school-level participation rates in the SBP. STATISTICAL ANALYSES: The Wilcoxon test was used for analysis of difference in change in mean SBP participation rate by experimental group. RESULTS: The median change in SBP participation rate between baseline and follow-up was 3% (interquartile range=13.5%) among the eight schools in the intervention group and 0.5% (interquartile range=0.7%) among the eight schools in the control group. This difference in change between groups was statistically significant (Wilcoxon test, P=0.03). The intervention effect increased throughout the intervention period, with change in mean SBP participation rate by the end of the school year reaching 10.3% (95% CI 3.0 to 17.6). However, among the intervention schools, the change in mean SBP participation rates was highly variable (range=-0.8% to 24.8%). CONCLUSIONS: Interventions designed to improve access to the SBP by reducing environmental and social barriers have potential to increase participation among high school students.

Long-term follow-up of the DeKAF cross-sectional cohort study.

The DeKAF study was developed to better understand the causes of late allograft loss. Preliminary findings from the DeKAF cross-sectional cohort (with follow-up < 20 months) have been published. Herein, we present long-term outcomes in those recipients (mean follow-up ± SD, 6.6 ± 0.7 years). Eligibility included being transplanted prior to October 1, 2005; serum creatinine ≤ 2.0 mg/dL on January 1, 2006; and subsequently developing new-onset graft dysfunction leading to a biopsy. Mean time from transplant to biopsy was 7.5 ± 6.1 years. Histologic findings and DSA were studied in relation to postbiopsy outcomes. Long-term follow-up confirms and expands the preliminary results of each of 3 studies: (1) increasing inflammation in area of atrophy (irrespective of inflammation in nonscarred areas [Banff i]) was associated with increasingly worse postbiopsy death-censored graft survival; (2) hierarchical analysis based on Banff scores defined clusters (entities) that differed in long-term death-censored graft survival; and (3) C4d-/DSA- recipients had significantly better (and C4d+/DSA+ worse) death-censored graft survival than other groups. C4d+/DSA- and C4d-/DSA+ had similar intermediate death-censored graft survival. Clinical and histologic findings at the time of new-onset graft dysfunction define high- vs low-risk groups for long-term death-censored graft survival, even years posttransplant. These findings can help differentiate groups for potential intervention studies.

Phylogeny with introgression in Habronattus jumping spiders (Araneae: Salticidae).

BACKGROUND: Habronattus is a diverse clade of jumping spiders with complex courtship displays and repeated evolution of Y chromosomes. A well-resolved species phylogeny would provide an important framework to study these traits, but has not yet been achieved, in part because the few genes available in past studies gave conflicting signals. Such discordant gene trees could be the result of incomplete lineage sorting (ILS) in recently diverged parts of the phylogeny, but there are indications that introgression could be a source of conflict. RESULTS: To infer Habronattus phylogeny and investigate the cause of gene tree discordance, we assembled transcriptomes for 34 Habronattus species and 2 outgroups. The concatenated 2.41 Mb of nuclear data (1877 loci) resolved phylogeny by Maximum Likelihood (ML) with high bootstrap support (95-100%) at most nodes, with some uncertainty surrounding the relationships of H. icenoglei, H. cambridgei, H. oregonensis, and Pellenes canadensis. Species tree analyses by ASTRAL and SVDQuartets gave almost completely congruent results. Several nodes in the ML phylogeny from 12.33 kb of mitochondrial data are incongruent with the nuclear phylogeny and indicate possible mitochondrial introgression: the internal relationships of the americanus and the coecatus groups, the relationship between the altanus, decorus, banksi, and americanus group, and between H. clypeatus and the coecatus group. To determine the relative contributions of ILS and introgression, we analyzed gene tree discordance for nuclear loci longer than 1 kb using Bayesian Concordance Analysis (BCA) for the americanus group (679 loci) and the VCCR clade (viridipes/clypeatus/coecatus/roberti groups) (517 loci) and found signals of introgression in both. Finally, we tested specifically for introgression in the concatenated nuclear matrix with Patterson's D statistics and DFOIL. We found nuclear introgression resulting in substantial admixture between americanus group species, between H. roberti and the clypeatus group, and between the clypeatus and coecatus groups. CONCLUSIONS: Our results indicate that the phylogenetic history of Habronattus is predominantly a diverging tree, but that hybridization may have been common between phylogenetically distant species, especially in subgroups with complex courtship displays.

Altering the School Breakfast Environment Reduces Barriers to School Breakfast Participation Among Diverse Rural Youth.

BACKGROUND: The purpose is to determine if altering school breakfast policies and the school breakfast environment will positively impact adolescent beliefs of the barriers and benefits of eating breakfast. METHODS: There were 904 adolescents from 16 rural high schools, Minnesota, in the BreakFAST Study who reported eating breakfast fewer than 4 times per week at baseline. Schools were randomized to intervention (N = 8 schools) or delayed intervention (N = 8) condition. The intervention lasted 1 school year. Students completed an online survey of beliefs of barriers and benefits to eating breakfast at baseline and follow-up. Summative scales were created. Bivariate and multivariate linear regression, accounting for clustering by school, was performed using SAS. Sex interaction was tested. Models tested the effect of the intervention on change in summative scales from baseline to follow -up. RESULTS: Participants were 54% female, 69.1% white, 36.6% eligible for free or reduced-price meals (FRM) and 13.1% of families received public assistance. The change in reported barriers was significantly different in intervention versus control schools (Net difference = 1.0, p = .03). There was no intervention effect of perceived benefits. CONCLUSIONS: A school-based policy and environmental change intervention can successfully reduce perceived barriers to eating school breakfast.

Late graft failure after kidney transplantation as the consequence of late versus early events.

Beyond the first posttransplant year, 3% of kidney transplants fail annually. In a prospective, multicenter cohort study, we tested the relative impact of early versus late events on risk of long-term death-censored graft failure (DCGF). In grafts surviving at least 90 days, early events (acute rejection [AR] and delayed graft function [DGF] before day 90) were recorded; serum creatinine (Cr) at day 90 was defined as baseline. Thereafter, a 25% rise in serum Cr or new-onset proteinuria triggered graft biopsy (index biopsy, IBx), allowing comparison of risk of DCGF associated with early events (AR, DGF, baseline serum Cr >2.0 mg/dL) to that associated with later events (IBx). Among 3678 patients followed for 4.7 ± 1.9 years, 753 (20%) had IBx at a median of 15.3 months posttransplant. Early AR (HR = 1.77, P < .001) and elevated Cr at Day 90 (HR = 2.56, P < .0001) were associated with increased risk of DCGF; however, later-onset dysfunction requiring IBx had far greater impact (HR = 13.8, P < .0001). At 90 days, neither clinical characteristics nor early events distinguished those who subsequently did or did not undergo IBx or suffer DCGF. To improve long-term kidney allograft survival, management paradigms should promote prompt diagnosis and treatment of both early and later events.

Increasing Social Support for Breakfast: Project BreakFAST.

High school students in the United States are known to be frequent skippers of breakfast. Social support is one key element needed to encourage adolescents to consume school breakfast. This article presents an analysis of the influence of a school policy and environment change intervention on the social support of adolescents to eat breakfast. METHOD: The intervention included school policy changes in 16 schools randomized to intervention and delayed-intervention conditions, in order to allow quick and easy access to breakfast as well as to allow breakfast consumption in classrooms and hallways; a School Breakfast Program marketing campaign to address normative and attitudinal beliefs; and increasing social support and role modeling to encourage breakfast eating. The participants in the study completed an online survey at baseline and again postintervention. RESULTS: The final analysis included only students who completed the relevant survey (n = 904) items on both the baseline and follow-up surveys. The students in the intervention group showed a higher level of social support post intervention than the control group with a significant adjusted p of .02. Most of the overall social support change was explained by a change in the "other kids at my school" and "other school staff" categories. CONCLUSIONS: The BreakFAST study shows the benefits of school staff and kids other than friends supporting a behavior change to include breakfast consumption in adolescents.

Barriers, Benefits, and Behaviors Related to Breakfast Consumption Among Rural Adolescents.

BACKGROUND: We sought to determine if perceived barriers, benefits, and modifiable behaviors support or interfere with breakfast consumption in a racially and economically diverse rural high school population. METHODS: The participants were 832 Minnesota adolescents from 16 rural high schools. We used baseline data from a group randomized trial aimed at increasing school breakfast participation through policy and environmental-level school changes. Students completed an online survey asking about demographics, breakfast eating behaviors, and the barriers and benefits of eating as it relates to school performance. Bivariate and multivariate logistic regression, accounting for clustering by school, was performed using SAS. Each scale was modeled independently. RESULTS: Participants were 9th and 10th grade students, 36% free/reduced-price lunch (FRL), 30% non-White, and 55% female. Breakfast skippers compared to nonbreakfast skippers reported fewer school related benefits and beliefs and more barriers to eating breakfast (p < .01). Adjusted models revealed students reported more positive beliefs (OR = 0.78, 95% CI = 0.73-0.83), more benefits (OR = 0.95, 95% CI = 0.93-0.97) and fewer barriers (OR = 0.85, 95% CI = 0.82-0.87) and were less likely to skip breakfast. CONCLUSIONS: Future intervention research should focus on alleviating barriers and enhancing education around the school related benefits of eating breakfast.

Prevalence of cardiovascular risk factors across six African Immigrant Groups in Minnesota.

BACKGROUND: Although African immigrants represent a large and growing segment of the U.S. population, there are little or no data available on the prevalence of cardiovascular disease (CVD) risk factors among this diverse population. This study compared the prevalence of self-reported CVD risk factors and health behaviors and examined the associations between immigration related characteristics and CVD risk factors and health behaviors across six African immigrants groups. METHODS: Data were from 996 African immigrants in the U.S., (37.9% Somalis; 26.8% Ethiopians; 14% Liberians; 8.5% Sudanese; 5.1% Kenyans and 7.8% others group) from a cross-sectional survey conducted in the Twin cities of Minnesota. Logistic regression models estimated the associations of demographic characteristics, and immigration-related factors (length of stay in the United states, English proficiency, income and health insurance) with prevalence of CVD risk factors (overweight/obese; hypertension and diabetes mellitus) and self-reported health behaviors (cigarette smoking, physical inactivity, conscious effort to exercise and eating a healthy diet). RESULTS: We found a relatively low self-reported prevalence of diabetes, hypertension, and smoking. However, significant differences were noted by country of origin. Using Somalis as our referent country of origin group, we found that Liberians and Kenyans were more likely to report having diabetes or hypertension. On all measures of health behaviors, Liberians were more likely to engage in more health protective behaviors than other individuals. CONCLUSIONS: Although African immigrants have different prevalence rates for CVD risk factors and health behaviors, there is a need to further explore the differences observed by country of emigration.

Development of three-dimensional shoulder kinematic and electromyographic exposure variation analysis methodology in violin musicians.

A total of 11 male and 19 female violinists performed 30-second random-ordered slow and fast musical repertoire while right shoulder three-dimensional kinematic, and upper trapezius and serratus anterior surface electromyography (EMG) data were summarised using exposure variation analysis (EVA), a bivariate distribution of work time spent at categories of signal amplitude, and duration spent at a fixed category of amplitude. Sixty-two per cent of intraclass correlation coefficients [1,1] for all kinematic and EMG variables exceeded 0.75, and 40% of standard error of the measurement results were below 5%, confirming EVA reliability. When fast repertoire was played, increases in odds ratios in short duration cells were seen in 23 of 24 possible instances, and decreases in longer duration cells were seen in 17 instances in all EVA arrays using multinomial logistic regression with random effects, confirming a shift towards shorter duration. A reliable technique to assess right shoulder kinematic and EMG exposure in violinists was identified. PRACTITIONER SUMMARY: A reliable method of measuring right shoulder motion and muscle activity exposure variation in violinists was developed which can be used to assess ergonomic risk in other occupations. Recently developed statistical methods enabled differentiation between fast and slow musical performance of standardised musical repertoire.

Transaxillary Nonendoscopic Subpectoral Augmentation Mammaplasty: A 10-Year Experience With Gel vs Saline in 2000 Patients-With Long-Term Patient Satisfaction Measured by the BREAST-Q.

BACKGROUND: Transaxillary augmentation mammaplasty (TAM) is an option for patients who wish to avoid a visible breast incision from breast augmentation (BA). OBJECTIVES: The authors compared TAM outcome data for gel and saline implants and evaluated patient satisfaction using the BREAST-Q patient-reported outcome measure (BQ). METHODS: In this 10-year retrospective, comparative, and cross-sectional study, the authors reviewed results of saline implants placed with TAM in a surgeon's practice during the final 5 years of the moratorium of the US Food and Drug Administration (phase 1) and compared them with results for gel and saline implants placed with TAM during the 5 years after the moratorium (phase 2). Outcomes were assessed for the entire BA study population (n = 2430 for primary BA; 4860 implants); 670 patients completed and returned the BQ, from which postoperative satisfaction was evaluated. RESULTS: BQ responses demonstrated a high rate of patient satisfaction, with outcomes comparable to those of other studies. The differences between the median BQ-assessed breast satisfaction and outcome satisfaction scores in the axillary and nonaxillary surgical groups were statistically significant, favoring axillary over nonaxillary. The difference in mean satisfaction scores was marginally significant between the 2 types of implants, favoring silicone gel. The incidence of surgical revision was 7.5% for the entire BA study population and 6.8% for the patients who underwent TAM. CONCLUSIONS: TAM produces long-term patient satisfaction as measured by the BQ. Complication rates are similar to those of other studies. In the present study, patients who underwent TAM and thus had hidden incisions were more satisfied than patients whose incisions were visible. LEVEL OF EVIDENCE: 3.

Maternal surfactant protein A influences the immunoprotective properties of milk in a murine model.

BACKGROUND: Maternal surfactant protein A (SP-A), a collectin with innate immune system function, is critical to newborn mouse survival preventing bacterial peritonitis associated with a nonhygienic environmental exposure. We hypothesized that SP-A improves newborn survival by optimizing milk immunoprotection. METHODS: Regional (lung) and systemic (milk and serum) immunologic responses to a novel antigen, 2,4-dintirophenyl keyhole limpet hemocyanin (DNP-KLH), and to a nonhygienic environment were evaluated in wild-type (WT) and SP-A null murine dams. Cross-fostering pups assessed the impact of milk on newborn survival. RESULTS: Maternal SP-A optimized antigen-specific milk secretory IgA (sIgA) production following the DNP-KLH exposure. Milk total and environment-specific sIgA production was not dependent on maternal SP-A in the nonhygienic exposure. At baseline, SP-A null milk contained physiologically meaningful increases in two proinflammatory cytokines compared with WT milk. The lack of SP-A plus the nonhygienic environmental exposure synergistically increased the number of proinflammatory cytokines contained in milk. Finally, the SP-A null genotype decreased pup survival during a nonhygienic environmental exposure. CONCLUSION: Maternal SP-A impacts milk sIgA and cytokine content, and is associated with improved newborn health.

Tacrolimus trough levels after month 3 as a predictor of acute rejection following kidney transplantation: a lesson learned from DeKAF Genomics.

Most calcineurin inhibitor (CNI)-based protocols reduce blood trough goals approximately 2-3 months post-transplant in clinically stable kidney transplant recipients. The CNI target trough level to prevent rejection, after reduction, is unknown. Using a multivariate Cox proportional hazards model, we determined the association of time-varying tacrolimus (TAC) trough levels with acute rejection (AR) occurring in the first 6 months post-transplant, but specifically we assessed this association after 3 months. A total of 1930 patients received TAC-based immunosuppression prior to AR in a prospective study. Of the 151 (7.8%) who developed AR, 47 developed AR after 3 months post-transplant. In an adjusted time-varying multivariate model, each 1 ng/ml decrease in TAC trough levels was associated with a 7.2% increased risk of AR [hazards ratio (HR) = 1.07, 95% confidence interval (CI) (1.01, 1.14) P = 0.03] in the first 6 months. There was an additional 23% increased risk of AR with each 1 ng/ml decrease in the TAC trough levels in months 3-6 [HR = 1.23, 95% CI (1.06, 1.43) P = 0.008]. In conclusion, lower TAC trough levels were significantly associated with increased risk of AR in the first 6 months post-transplant with additional risk of AR between months 3 and 6 post-transplant. The timing and practice of TAC dose reduction should be personalized based on the individual's risk factors.

Multiple origins of sex chromosome fusions correlated with chiasma localization in Habronattus jumping spiders (Araneae: Salticidae).

Entelegyne spiders rarely show fusions yielding neo-Y chromosomes, which M. J. D. White attributed to a constraint in spiders, namely their proximal chiasma localization acting to upset meiotic segregation in males with fusions. Of the 75 taxa of Habronattus and outgroups studied, 47 have X1 X2 0 sex chromosomes in males, 10 have X1 X2 Y, 15 have X1 X2 X3 Y, 2 have X0, and one has both X1 X2 0 and X1 X2 X3 Y. Chromosome numbers and behavior suggest neo-Ys formed by an autosome-X fusion to make X1 X2 Y, with a second fusion to an autosome to make X1 X2 X3 Y. Phylogeny shows at least 8-15 gains (or possibly some losses) of neo-Y (i.e., X-autosome fusions), a remarkable number for such a small clade. In contrast to the many X-autosome fusions, at most one autosome-autosome fusion is indicated. Origins of neo-Y are correlated significantly with distal localization of chiasmata, supporting White's hypothesis that evolution of neo-Y systems is facilitated by looser pairing (distal chiasmata) at meiosis. However, an alternative (or contributing) explanation for the correlation is that X-autosome fusions were selected to permit isolation of male-favored alleles to the neo-Y chromosome, aided by distal chiasmata limiting recombination. This intralocus sexual conflict hypothesis could explain both the many X-autosome fusions, and the stunning complexity of male Habronattus courtship displays.