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Objectives Early treatment of individuals at risk of developing rheumatoid arthritis (RA-risk) in the preclinical phase has the potential to positively impact both patients and society by preventing disease onset and improving patients’ quality of life. The PRAIRI study was a randomised, double-blind, placebo-controlled trial with the B-cell depleting agent rituximab (RTX), which resulted in a significant delay of arthritis development of up to 12 months in seropositive RA-risk individuals. Here, we report our findings on patient-reported outcomes (PROs) in this study population.Methods Seventy-eight RA-risk individuals were treated with one single dose of either placebo (PBO) or 1000 mg RTX plus 100 mg methylprednisolone (MP) and anti-histamines, regardless of treatment allocation, as co-medication. Data on quality of life were collected at baseline and 1, 4, 6, 12 and 24 months using established PRO questionnaires (visual analogue scale (VAS) pain, health assessment questionnaire disability index (HAQ-DI) score, EuroQol five dimension (EQ-5D) and both physical and mental component score of the 36-item short-form heath survey (SF-36)).Results No significant changes in quality of life over a 2 year follow-up were observed in at-risk individuals treated with RTX compared to PBO given the PRO scores at 24 months (mean difference±SEM: HAQ score=0.07±0.16; EQ-5D=−0.02±0.05; VAS pain=11.11±7.40). Furthermore, no significant effect of treatment on perceived arthritis severity at the time of clinically manifest disease (arthritis) was found.Conclusion One single dose of RTX plus MP administered to RA-risk individuals does not have a meaningful and measurable positive effect on PROs after 2 years of follow-up and/or perceived disease severity at the time of arthritis development.Trial registration number Trial registered at EU Clinical Trial Register, EudraCT Number: 2009-010955-29 (https://www.clinicaltrialsregister.eu/ctr-search/search?query=Prevention+of+RA+by+B+cell+directed+therapy).

Objective To evaluate the long-term sustainability of response to the Janus kinase inhibitor upadacitinib among patients with rheumatoid arthritis and an inadequate response or intolerance to biological disease-modifying antirheumatic drugs (bDMARD-IR) in the SELECT-BEYOND phase 3 trial.Methods Patients on background conventional synthetic DMARDs (csDMARDs) were treated once daily with upadacitinib 15 mg or placebo. Patients who completed the week 24 visit could enter a long-term extension of up to 5 years. The sustainability of response was assessed based on achievement of Clinical Disease Activity Index (CDAI), Simplified Disease Activity Index (SDAI) and Disease Activity Score 28-joint count using C-reactive protein (DAS28 (CRP)) targets and evaluated up to week 260 in all patients receiving the approved upadacitinib 15 mg dose, including those randomised to upadacitinib 15 mg and those who switched from placebo to upadacitinib 15 mg at week 12.Results In this bDMARD-IR population, 45% (n=104/229) and 79% (n=172/219) of patients treated with upadacitinib 15 mg plus background csDMARD(s) achieved CDAI remission or CDAI low disease activity (LDA) at any point during the 5-year study, respectively. Of those who achieved CDAI remission/LDA, 25%/43% maintained their initial response through 240 weeks of follow-up after first achieving response. Most patients who lost remission or LDA were able to recapture that response by the cut-off date. Similar overall results were observed for SDAI and DAS28 (CRP). No strong predictors of response were identified.Conclusions Over three-quarters of bDMARD-IR patients achieved CDAI LDA with upadacitinib, and almost half of those maintained LDA through 240 weeks of follow-up. Remission was achieved by nearly half of all patients and maintained in approximately a quarter of those achieving remission.Trial registration number NCT02706847.

Objective This report from the NORD-STAR (Nordic Rheumatic Diseases Strategy Trials and Registries) trial aimed to determine if obesity is associated with response to conventional and biological antirheumatic treatment in early rheumatoid arthritis (RA).Methods This report included 793 participants with untreated early RA from the randomised, longitudinal NORD-STAR trial, all of whom had their body mass index (BMI) assessed at baseline. Obesity was defined as BMI ≥30 kg/m2. All participants were randomised 1:1:1:1 to one of four treatment arms: active conventional treatment, certolizumab-pegol, abatacept and tocilizumab. Clinical and laboratory measurements were performed at baseline and at 8, 12, 24 and 48-week follow-up. The primary endpoint for this report was response to treatment based on Clinical Disease Activity Index (CDAI) and Simple Disease Activity Index (SDAI) remission and Disease Activity Score with 28 joints using C-reactive protein (DAS28-CRP)

Objective Evidence indicates reduced treatment effectiveness of TNFi in women with axial spondyloarthritis (axSpA) compared with men. We aimed to investigate sex differences in treatment response and retention rates over 24 months of follow-up in axSpA patients initiating their first TNFi.Methods Data from axSpA patients initiating a TNFi in 1 of 15 registries within EuroSpA collaboration were pooled. We investigated the association of sex with treatment response using logistic regression. The primary outcome was clinically important improvement (CII) at 6 months according to Ankylosing Spondylitis Disease Activity Score with C-reactive protein (CRP) (≥1.1 decrease). We adjusted for age, country and TNFi start year. A secondary outcome was retention rates over 24 months of follow-up assessed by Kaplan-Meier estimator.Results In total, 6451 axSpA patients with data on CII were assessed for treatment response; 2538 (39%) were women and 3913 (61%) were men. Women presented at baseline with lower CRP levels but had higher scores on patient-reported outcome measures. At 6 months, 53% of the women and 66% of the men had CII. Women had a lower relative risk of CII compared with men (0.81; 95% CI 0.77 to 0.84). This sex difference was similar in adjusted analysis (0.85; 95% CI 0.82 to 0.88). Retention rates were evaluated in 27 702 patients. The TNFi 6/12/24 months retention rates were significantly lower among women (79%/66%/53%) than men (88%/79%/69%).Conclusion Treatment response and retention rates are lower among women with axSpA initiating their first TNFi. Sex differences in treatment effectiveness were present regardless of the outcome measure used for treatment response, and differences in retention rates transpired early and increased as time progressed.

Abstract Elite middle distance runners present as a unique population in which to explore biomechanical phenomena in relation to running speed, as their training and racing spans a broad spectrum of paces. However, there have been no comprehensive investigations of running mechanics across speeds within this population. Here, we used the spring-mass model of running to explore global mechanical behavior across speeds in these runners. Ten elite-level 1500 m and mile runners (mean 1500 m best: 3:37.3 ± 3.6 s; mile: 3:54.6 ± 3.9 s) and ten highly trained 1500 m and mile runners (mean 1500 m best: 4:07.6 ± 3.7 s; mile: 4:27.4 ± 4.1 s) ran on a treadmill at 10 speeds where temporal measures were recorded. Spatiotemporal and spring-mass characteristics and their corresponding variation were calculated within and across speeds. All spatiotemporal measures changed with speed in both groups, but the changes were less substantial in the elites. The elite runners ran with greater approximated vertical forces (+ 0.16 BW) and steeper impact angles (+ 3.1°) across speeds. Moreover, the elites ran with greater leg and vertical stiffnesses (+ 2.1 kN/m and + 3.6 kN/m) across speeds. Neither group changed leg stiffness with increasing speeds, but both groups increased vertical stiffness (1.6 kN/m per km/h), and the elite runners more so (further + 0.4 kN/m per km/h). The elite runners also demonstrated lower variability in their spatiotemporal behavior across speeds. Together, these findings suggested that elite middle distance runners may have distinct global mechanical patterns across running speeds, where they behave as stiffer, less variable spring-mass systems compared to highly trained, but sub-elite counterparts.

BackgroundThe Onduo virtual care program for people with type 2 diabetes (T2D) includes a mobile app, remote lifestyle coaching, connected devices, and telemedicine consultations with endocrinologists for medication management and prescription of real-time continuous glucose monitoring (RT-CGM) devices. In a previously described 4-month prospective study of this program, adults with T2D and baseline glycated hemoglobin (HbA1c) ≥8.0% to ≤12.0% experienced a mean HbA1c decrease of 1.6% with no significant increase in hypoglycemia. ObjectiveThe objective of this analysis was to evaluate medication optimization and management in the 4-month prospective T2D study. MethodsStudy participants received at least 1 telemedicine consultation with an Onduo endocrinologist for diabetes medication management and used RT-CGM intermittently to guide therapy and dosing. Medication changes were analyzed. ResultsOf 55 participants, 48 (87%) had a medication change consisting of a dose change, addition, or discontinuation. Of these, 15 (31%) participants had a net increase in number of diabetes medication classes from baseline. Mean time to first medication change for these participants was 36 days. The percentage of participants taking a glucagon-like peptide-1 receptor agonist increased from 25% (12/48) to 56% (n=27), while the percentages of participants taking a sulfonylurea or dipeptidyl peptidase 4 inhibitor decreased from 56% (n=27) to 33% (n=16) and 17% (n=8) to 6% (n=3), respectively. Prescriptions of other antidiabetic medication classes including insulin did not change significantly. ConclusionsThe Onduo virtual care program can play an important role in providing timely access to guideline-based diabetes management medications and technologies for people with T2D. Trial RegistrationClinicalTrials.gov NCT03865381; https://clinicaltrials.gov/ct2/show/NCT03865381

Introduction: The purpose of the study was to determine the preventable trauma-related death rate (PDR) at Komfo Anokye Teaching Hospital in Kumasi, Ghana three years after initiation of an Emergency Medicine (EM) residency Method: This was a retrospective, cross-sectional study. A multidisciplinary panel of physicians completed a structured implicit review of clinical data for trauma patients who died during the period 2011 to 2012. The panel judged the preventability of each death and the nature of inappropriate care. Categories were definitely preventable (DP), possibly preventable (PP), and not preventable (NP). Results: 1) The total number of cases was forty-five; 36 cases had adequate data for review. Subjects were predominately male; road traffic injury (RTI) was the leading mechanism of injury. Four cases (11.1%) were DP, 14 cases (38.9%) were PP and 18 (50%) were NP. Hemorrhage was the leading cause of death (39%). Among DP/PP deaths there were 37 instances of inappropriate care. Delay in surgical intervention was the predominate event (50%). 2) The PDR for this study was 50% (0.95 CI, 33.7%–66.3%) Conclusion: Fifty percent of trauma deaths were DP/PP. Multiple episodes of varying types of inappropriate care occurred. More efficient surgical evaluation and appropriate treatment of hemorrhage could reduce trauma morality. Large amounts of missing and incomplete clinical data suggest considerable selection bias. A major implication of this study is the importance of having a robust, prospective trauma registry to collect clinical information to increase the number of cases for review. Keywords: Emergency medicine Ghana, Trauma care, Tertiary care Ghana, Structured panel review, Trauma-related death

Non-Hispanic (NH) Black, American Indian/Alaska Native (Indigenous), and NH-White men have the highest colorectal cancer (CRC) mortality rates among all other racial/ethnic groups. Contributing factors are multifaceted, yet no studies have examined the psychometric properties of a comprehensive survey examining potential masculinity barriers to CRC screening behaviors among these populations. This study assessed the psychometric properties of our Masculinity Barriers to Medical Care (MBMC) Scale among NH-Black, Indigenous, and NH-White men who completed our web-based MBMC, Psychosocial Factors, and CRC Screening Uptake & Intention Survey. We conducted exploratory factor analysis on a sample of 254 men and multivariate analysis of variance (MANOVA) on a separate sample of 637 men nationally representative by age and state of residence. After psychometric assessment, the MBMC scale was reduced from 24 to 18 items and from six to four subscales. NH-Black men’s mean scores were lowest on three of four subscales (Being Strong, Negative and Positive Attitudes) and highest on the Acknowledging Emotions subscale. Compared with both Indigenous and NH-White men, NH-Black men had significantly lower Negative Attitudes subscale scores and significantly higher scores on the Acknowledging Emotions subscale. Compared with both Indigenous and NH-Black men, NH-White men had significantly higher Being Strong and Positive Attitudes subscales scores. This study expands on previous research indicating that, among racialized populations of men, endorsement of traditional masculine ideologies influences engagement in preventive health behaviors. Our scale can be tailored to assess attitudes to screening for other cancers and diseases that disproportionately burden medically underserved populations.

We summarised four pivotal Randomised Controlled Trials (RCTs) with antirheumatic drugs on the secondary prevention of cardiovascular events. The favourable effects of canakinumab and colchicine confirm (low-grade) inflammation as an independent risk factor for cardiovascular events. While colchicine might be the first drug in the clinic, we expect that this is only the first in a future series of anti-inflammatory drugs used in secondary prevention of cardiovascular events.

The gallbladder normally lies within a fossa on the visceral surface of the liver. The primary purpose of this study was to determine whether the volume of this fossa was reduced after cholecystectomy. Livers were obtained from embalmed cadavers of 19 females and 15 males with a mean age of 84.1 ± 10.8 yrs. The presence of a gallbladder was assessed, the volume of the irregularly-shaped gallbladder fossa determined from a mold of the fossa, and the dimensions of each fossa were estimated. The mean volume of gallbladder fossae from livers with gallbladders (n = 26; 13 females and 13 males) was 31.01 ± 17.82 ml, which was significantly greater than fossae in livers without gallbladders (n = 8, 6 females, 2 males) which was 8.75 ± 4.72 ml (P

Background: There are concerns that the use of antibiotics before, during or immediately after pregnancy may have adverse effects on the neonatal gut microbiome and adversely affect the development of the infant immune system, leading to the development of childhood allergy, asthma, atopic disease and obesity. Methods: In this narrative review, we have explored a number of hypotheses, including the “Barker hypothesis”, the “hygiene hypothesis”, the link between inflammation and metabolic disease, and the influence of the neonatal gut microbiota on the development of the immune system in infants. Results: We found evidence to link the use of antibiotics before, during or immediately after pregnancy with an increased risk of childhood allergy, asthma, atopy and obesity. Conclusions: Although we found robust evidence to link antibiotic use in pregnancy with obesity and an “allergic triad” of asthma, eczema and hay fever, care must be taken when interpreting the findings because of the lack of adjustment for confounding variables in published studies. These may be (i) whether or not the mother had the same outcome variable (for example, asthma) as the infant, for which the mother may have received the antibiotics; (ii) the indication, timing or number of antibiotic courses given; (iii) the use of broad-spectrum or narrow-range antibiotics; (iv) the dose-dependent nature of the effector; and (v) the class of antibiotics used.

Abstract The emerging technique termed functional identification of target by expression proteomics (FITExP) has been shown to identify the key protein targets of anti-cancer drugs. Here, we use this approach to elucidate the proteins involved in the mechanism of action of two ruthenium(II)-based anti-cancer compounds, RAPTA-T and RAPTA-EA in breast cancer cells, revealing significant differences in the proteins upregulated. RAPTA-T causes upregulation of multiple proteins suggesting a broad mechanism of action involving suppression of both metastasis and tumorigenicity. RAPTA-EA bearing a GST inhibiting ethacrynic acid moiety, causes upregulation of mainly oxidative stress related proteins. The approach used in this work could be applied to the prediction of effective drug combinations to test in cancer chemotherapy clinical trials.

Field trials were conducted in July–August and October 2012 to quantify the inactivation rate of Escherichia coli O157:H7 when mixed with fecal slurry and applied to romaine lettuce leaves. Lettuce was grown under commercial conditions in Salinas Valley, California. One-half milliliter of rabbit, chicken, or pig fecal slurry, containing an average of 4.05 × 107 CFU E. coli O157:H7 (C0), was inoculated onto the upper (adaxial) surface of a lower leaf on 288 heads of lettuce per trial immediately following a 2.5 h irrigation event. To estimate the bacterial inactivation rate as a function of time, fecal matrix, irrigation and seasonal climate effects, sets of lettuce heads (n = 28) were sampled each day over 10 days and the concentration of E. coli O157:H7 (Ct) determined. E. coli O157:H7 was detected on 100% of heads during the 10-day duration, with concentrations ranging from ≤340 MPN/head (∼5-log reduction) to >3.45 × 1012 MPN/head (∼5-log growth). Relative to C0, on day 10 (Ct = 12) we observed an overall 2.6-log and 3.2-log mean reduction of E. coli O157:H7 in July and October, respectively. However, we observed relative maximum concentrations due to bacterial growth on day 6 (maximum Ct = 8) apparently stimulated by foliar irrigation on day 5. From this maximum there was a mean 5.3-log and 5.1-log reduction by day 10 (Ct = 12) for the July and October trials, respectively. This study provides insight into the inactivation and growth kinetics of E. coli O157:H7 on romaine lettuce leaves under natural field conditions. This study provides evidence that harvesting within 24 h post irrigation has the potential to increase the concentration of E. coli O157:H7 contamination, if present on heads of romaine lettuce; foliar irrigation can temporarily stimulate substantial regrowth of E. coli O157:H7.

The Conformity to Masculine Norms Inventory (CMNI) is a widely used multidimensional scale. Studies using the CMNI most often report only total scale scores, which are predominantly associated with negative outcomes. Various studies since the CMNI’s inception in 2003 using subscales have reported both positive and negative outcomes. The current content analysis examined studies ( N = 17) correlating the 11 subscales with 63 criterion variables across 7 categories. Most findings were consistent with past research using total scale scores that reported negative outcomes. For example, conformity to masculine norms has been inversely related to help-seeking and positively correlated with concerning health variables, such as substance use. Nonetheless, past reliance on total scores has obscured the complexity of associations with the CMNI in that 30% of the findings in the present study reflected positive outcomes, particularly for health promotion. Subscales differed in their relationships with various outcomes: for one subscale they were predominantly positive, but six others were mostly negative. The situational and contextual implications of conformity to masculine norms and their relationships to positive and negative outcomes are discussed.

This study characterizes the clinical and morphofunctional effects of a 5α-reductase inhibitor on steroid hormone receptors in normal human prostate tissue, as potential mediators of the clinical effects of dutasteride. This work was a prospective, double-blind, and randomized study that evaluated 49 men aged between 45 and 70 years, with no alterations in a digital rectal examination and prostate-specific antigen measurements between 2.5 and 4.0 ng/mL. These patients underwent prostate biopsy guided by transretal ultrasound with prostate neoplasia being ruled out, and the patients were divided into two groups, with one group receiving dutasteride ( n = 25) and one group receiving a placebo ( n = 24). The patients were clinically assessed each quarter, and at the end of 12 months they underwent new laboratory tests, prostate rebiopsy, and histopathological, immunohistochemical and clinical analyses. The estrogen receptor-beta (ERβ) and androgen receptor immunoreactivities were higher, and the proliferation/apoptotic ratio was significantly lower with predominance of the apoptotic process, followed by a significant reduction in the prostate volume and the total serum prostate-specific antigen levels in the dutasteride group when compared with the placebo group, with a clear supremacy of ERβ. There were no significant variations in the serum estrogen and testosterone levels, in the body mass index, or in the ERα immunoreactivities in the dutasteride and placebo groups. The results demonstrated the importance of the ERβ pathway in the activation mechanisms of apoptosis, exerting a protective effect in the normal prostate, indicating that this receptor might be an important mediator of the clinical effects of dutasteride.

OBJECTIVES:To investigate the safety of ofatumumab retreatment in rheumatoid arthritis. METHODS:Patients with active rheumatoid arthritis participating in two phase III trials (OFA110635 and OFA110634) and a phase II extension trial (OFA111752) received individualised open-label ofatumumab retreatment (700 mg X 2 intravenous infusions two weeks apart) ≥24 weeks following the first course and ≥16 weeks following further courses. Retreatment required evidence of clinical response followed by disease relapse. These studies were prematurely terminated by the sponsor to refocus development on subcutaneous delivery. Due to differences in study designs and populations, data are summarised separately for each study. RESULTS:483 patients (243, 148 and 92 in OFA110635, OFA110634 and OFA111752 respectively) received up to 7 treatment courses of intravenous ofatumumab; cumulative duration of exposure was 463, 182 and 175 patient-years, respectively. Mean time between courses was 17-47 weeks. Ofatumumab induced a profound depletion of peripheral B-lymphocytes. Retreated patients derived benefit based on improvement in DAS28. Adverse events were reported for 93% (226/243), 91% (134/148) and 76% (70/92), serious adverse events for 18% (44/243), 20% (30/148) and 12% (11/92) and serious infections for 3% (8/243), 5% (7/148) and 1% (1/92) of patients in OFA110635, OFA110634 and OFA111752, respectively. The most common adverse events were infusion-related reactions during the first infusion of the first course (48-79%); serious infusion-related reactions were rare (

Pottery is a mainstay of archaeological analysis worldwide. Often, high proportions of the pottery recovered from a given site are decorated in some manner. In northern Iroquoia, late pre-contact pottery and early contact decoration commonly occur on collars-thick bands of clay that encircle a pot and extend several centimeters down from the lip. These decorations constitute signals that conveyed information about a pot's user(s). In southern Ontario the period A.D. 1350 to 1650 witnessed substantial changes in socio-political and settlement systems that included population movement, coalescence of formerly separate communities into large villages and towns, waxing and waning of regional strife, the formation of nations, and finally the development of three confederacies that each occupied distinct, constricted areas. Social network analysis demonstrates that signaling practices changed to reflect these regional patterns. Networks become more consolidated through time ultimately resulting in a "small world" network with small degrees of separation between sites reflecting the integration of communities within and between the three confederacies.

Advances in molecular biology, microfluidics, and laboratory automation continue to expand the accessibility and applicability of these methods beyond the confines of conventional, centralized laboratory facilities and into point of use roles in clinical, military, forensic, and field-deployed applications. As a result, there is a growing need to adapt the unit operations of molecular biology (e.g., aliquoting, centrifuging, mixing, and thermal cycling) to compact, portable, low-power, and automation-ready formats. Here we present one such adaptation, the rotary zone thermal cycler (RZTC), a novel wheel-based device capable of cycling up to four different fixed-temperature blocks into contact with a stationary 4-microliter capillary-bound sample to realize 1-3 second transitions with steady state heater power of less than 10 W. We demonstrate the utility of the RZTC for DNA amplification as part of a highly integrated rotary zone PCR (rzPCR) system that uses low-volume valves and syringe-based fluid handling to automate sample loading and unloading, thermal cycling, and between-run cleaning functionalities in a compact, modular form factor. In addition to characterizing the performance of the RZTC and the efficacy of different online cleaning protocols, we present preliminary results for rapid single-plex PCR, multiplex short tandem repeat (STR) amplification, and second strand cDNA synthesis.

This study was designed to replicate the study of Levant, Wimer, and Williams (2011), which reported complex relationships between masculinity and health behaviors using a more diverse sample and updated measures. A sample of 589 college and community-dwelling men responded to an online survey consisting of five scales. Levant et al.’s (2011) study was partially replicated—some masculinity constructs were identified as protective buffers for some health behaviors and others as risk factors. The vast majority of the findings that were replicated were risk factors, suggesting that traditional masculinity is more of risk than a buffer, and occurred in the analyses involving Avoiding Anger and Stress and Avoiding Substance Use subscales, suggesting that these health behaviors are most closely associated with masculinity. The results are discussed in terms of limitations, suggestions for future research, and implications for health care practice.

Low-carbon biofuel sources are being developed and evaluated in the United States and Europe to partially offset petroleum transport fuels. Current and potential biofuel production systems were evaluated from a long-term continuous no-tillage corn (Zea mays L.) and switchgrass (Panicum virgatum L.) field trial under differing harvest strategies and nitrogen (N) fertilizer intensities to determine overall environmental sustainability. Corn and switchgrass grown for bioenergy resulted in near-term net greenhouse gas (GHG) reductions of -29 to -396 grams of CO2 equivalent emissions per megajoule of ethanol per year as a result of direct soil carbon sequestration and from the adoption of integrated biofuel conversion pathways. Management practices in switchgrass and corn resulted in large variation in petroleum offset potential. Switchgrass, using best management practices produced 3919±117 liters of ethanol per hectare and had 74±2.2 gigajoules of petroleum offsets per hectare which was similar to intensified corn systems (grain and 50% residue harvest under optimal N rates). Co-locating and integrating cellulosic biorefineries with existing dry mill corn grain ethanol facilities improved net energy yields (GJ ha-1) of corn grain ethanol by >70%. A multi-feedstock, landscape approach coupled with an integrated biorefinery would be a viable option to meet growing renewable transportation fuel demands while improving the energy efficiency of first generation biofuels.

In obese women, 1) to assess whether lower gestational weight gain (GWG) during pregnancy in the lifestyle intervention group of a randomized controlled trial (RCT) resulted in differences in offspring anthropometrics and body composition, and 2) to compare offspring outcomes to a reference group of children born to women with a normal Body Mass Index (BMI).The LiPO (Lifestyle in Pregnancy and Offspring) study was an offspring follow-up of a RCT with 360 obese pregnant women with a lifestyle intervention during pregnancy including dietary advice, coaching and exercise. The trial was completed by 301 women who were eligible for follow-up. In addition, to the children from the RCT, a group of children born to women with a normal BMI were included as a reference group. At 2.8 (range 2.5-3.2) years, anthropometrics were measured in 157 children of the RCT mothers and in 97 reference group children with Body Mass Index (BMI) Z-score as a primary outcome. Body composition was estimated by Dual Energy X-ray (DEXA) in 123 successful scans out of 147 (84%).No differences between randomized groups were seen in mean (95% C.I.) BMI Z-score (intervention group 0.06 [-0.17; 0.29] vs. controls -0.18 [-0.43; 0.05]), in the percentage of overweight or obese children (10.9% vs. 6.7%), in other anthropometrics, or in body composition values by DEXA. Outcomes between children from the RCT and the reference group children were not significantly different.The RCT with lifestyle intervention in obese pregnant women did not result in any detectable effect on offspring anthropometrics or body composition by DEXA at 2.8 years of age. This may reflect the limited difference in GWG between intervention and control groups. Offspring of obese mothers from the RCT were comparable to offspring of mothers with a normal BMI.

The present study examined whether previous findings linking masculinity constructs and health behaviors applied to a relatively recent health risk behavior for men, the consumption of energy drinks. In addition, it also examined whether self-identifying as a jock and being a member of a fraternity would moderate the relationships between masculinity constructs and energy drink consumption. A total of 589 men completed measures of three masculinity constructs (endorsement of traditional masculinity ideology, conformity to masculine norms, and gender role conflict), energy drink consumption, jock identity, and fraternity membership, in addition to a demographic questionnaire. Age, endorsement of traditional masculinity ideology, and conforming to the masculine norms of risk taking and primacy of work were identified to be significant predictors of energy drink consumption. Furthermore, jock identity moderated the relationship between the endorsement of traditional masculinity ideology and energy drink consumption whereas fraternity membership moderated the relationship between conforming to the masculine norm of violence and energy drink consumption. Limitations, implications, and potential future directions are discussed.

Next-generation sequencing (NGS) is emerging as a powerful tool for elucidating genetic information for a wide range of applications. Unfortunately, the surging popularity of NGS has not yet been accompanied by an improvement in automated techniques for preparing formatted sequencing libraries. To address this challenge, we have developed a prototype microfluidic system for preparing sequencer-ready DNA libraries for analysis by Illumina sequencing. Our system combines droplet-based digital microfluidic (DMF) sample handling with peripheral modules to create a fully-integrated, sample-in library-out platform. In this report, we use our automated system to prepare NGS libraries from samples of human and bacterial genomic DNA. E. coli libraries prepared on-device from 5 ng of total DNA yielded excellent sequence coverage over the entire bacterial genome, with >99% alignment to the reference genome, even genome coverage, and good quality scores. Furthermore, we produced a de novo assembly on a previously unsequenced multi-drug resistant Klebsiella pneumoniae strain BAA-2146 (KpnNDM). The new method described here is fast, robust, scalable, and automated. Our device for library preparation will assist in the integration of NGS technology into a wide variety of laboratories, including small research laboratories and clinical laboratories.

An important feature of addiction is the high drug craving that may promote the continuation of consumption. Environmental stimuli classically conditioned to drug-intake have a strong motivational power for addicts and can elicit craving. However, addicts differ in the attitudes towards their own consumption behavior: some are content with drug taking (consonant users) whereas others are discontent (dissonant users). Such differences may be important for clinical practice because the experience of dissonance might enhance the likelihood to consider treatment. This fMRI study investigated in smokers whether these different attitudes influence subjective and neural responses to smoking stimuli. Based on self-characterization, smokers were divided into consonant and dissonant smokers. These two groups were presented smoking stimuli and neutral stimuli. Former studies have suggested differences in the impact of smoking stimuli depending on the temporal stage of the smoking ritual they are associated with. Therefore, we used stimuli associated with the beginning (BEGIN-smoking-stimuli) and stimuli associated with the terminal stage (END-smoking-stimuli) of the smoking ritual as distinct stimulus categories. Stimulus ratings did not differ between both groups. Brain data showed that BEGIN-smoking-stimuli led to enhanced mesolimbic responses (amygdala, hippocampus, insula) in dissonant compared to consonant smokers. In response to END-smoking-stimuli, dissonant smokers showed reduced mesocortical responses (orbitofrontal cortex, subcallosal cortex) compared to consonant smokers. These results suggest that smoking stimuli with a high incentive value (BEGIN-smoking-stimuli) are more appetitive for dissonant than consonant smokers at least on the neural level. To the contrary, smoking stimuli with low incentive value (END-smoking-stimuli) seem to be less appetitive for dissonant smokers than consonant smokers. These differences might be one reason why dissonant smokers experience difficulties in translating their attitudes into an actual behavior change.

High-frequency, low-magnitude vibration enhances bone formation ostensibly by mimicking normal postural muscle activity. We tested this hypothesis by examining whether daily exposure to low-magnitude vibration (VIB) would maintain bone in a muscle disuse model with botulinum toxin type A (BTX). Female 16-18 wk old BALB/c mice (N = 36) were assigned to BTX-VIB, BTX-SHAM, VIB, or SHAM. BTX mice were injected with BTX (20 µL; 1 U/100 g body mass) into the left hindlimb posterior musculature. All mice were anaesthetized for 20 min/d, 5 d/wk, for 3 wk, and the left leg mounted to a holder. Through the holder, VIB mice received 45 Hz, ± 0.6 g sinusoidal acceleration without weight bearing. SHAM mice received no vibration. At baseline and 3 wk, muscle cross-sectional area (MCSA) and tibial bone properties (epiphysis, metaphysis and diaphysis) were assessed by in vivo micro-CT. Bone volume fraction in the metaphysis decreased 12 ± 9% and 7 ± 6% in BTX-VIB and BTX-SHAM, but increased in the VIB and SHAM. There were no differences in dynamic histomorphometry outcomes between BTX-VIB and BTX nor between VIB and SHAM. Thus, vibration did not prevent bone loss induced by a rapid decline in muscle activity nor produce an anabolic effect in normal mice. The daily loading duration was shorter than would be expected from postural muscle activity, and may have been insufficient to prevent bone loss. Based on the approach used in this study, vibration does not prevent bone loss in the absence of muscle activity induced by BTX.

Spinosad is a natural insecticide with desirable qualities, and it is widely used as an alternative to organophosphates for control of pests such as the melon fly, Bactrocera cucurbitae (Coquillett). To monitor the potential for development of resistance, information about the current levels of tolerance to spinosad in melon fly populations were established in this study. Spinosad tolerance bioassays were conducted using both topical applications and feeding methods on flies from field populations with extensive exposure to spinosad as well as from collections with little or no prior exposure. Increased levels of resistance were observed in flies from the field populations. Also, higher dosages were generally required to achieve specific levels of mortality using topical applications compared to the feeding method, but these levels were all lower than those used for many organophosphate-based food lures. Our information is important for maintaining effective programs for melon fly management using spinosad.

Changes in whole body energy levels are closely linked to alterations in body weight and bone mass. Here, we show that hypothalamic signals contribute to the regulation of bone mass in a manner consistent with the central perception of energy status. Mice lacking neuropeptide Y (NPY), a well-known orexigenic factor whose hypothalamic expression is increased in fasting, have significantly increased bone mass in association with enhanced osteoblast activity and elevated expression of bone osteogenic transcription factors, Runx2 and Osterix. In contrast, wild type and NPY knockout (NPY (-/-)) mice in which NPY is specifically over expressed in the hypothalamus (AAV-NPY+) show a significant reduction in bone mass despite developing an obese phenotype. The AAV-NPY+ induced loss of bone mass is consistent with models known to mimic the central effects of fasting, which also show increased hypothalamic NPY levels. Thus these data indicate that, in addition to well characterized responses to body mass, skeletal tissue also responds to the perception of nutritional status by the hypothalamus independently of body weight. In addition, the reduction in bone mass by AAV NPY+ administration does not completely correct the high bone mass phenotype of NPY (-/-) mice, indicating the possibility that peripheral NPY may also be an important regulator of bone mass. Indeed, we demonstrate the expression of NPY specifically in osteoblasts. In conclusion, these data identifies NPY as a critical integrator of bone homeostatic signals; increasing bone mass during times of obesity when hypothalamic NPY expression levels are low and reducing bone formation to conserve energy under 'starving' conditions, when hypothalamic NPY expression levels are high.