Search

Outbreaks of coronavirus infectious disease 2019 (COVID-19) in meat processing plants and media reports of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection on foods have raised concerns of a public health risk from contaminated foods. We used herpes simplex virus 1, a non-Biosafety Level 3 (non-BSL3) enveloped virus, as a surrogate to develop and validate methods before assessing the survival of infectious SARS-CoV-2 on foods. Several food types, including chicken, seafood, and produce, were held at 4 °C and assessed for infectious virus survival (herpes simplex virus 1 (HSV-1) and SARS-CoV-2) at 0 h, 1 h, and 24 h post-inoculation (hpi) by plaque assay. At all three time points, recovery of SARS-CoV-2 was similar from chicken, salmon, shrimp, and spinach, ranging from 3.4 to 4.3 log PFU/mL. However, initial (0 h) virus recovery from apples and mushrooms was significantly lower than that from poultry and seafood, and infectious virus decreased over time, with recovery from mushrooms becoming undetectable by 24 hpi. Comparing infectious virus titers with viral genome copies confirmed that PCR-based tests only indicate presence of viral nucleic acid, which does not necessarily correlate with the quantity of infectious virus. The survival and high recovery of SARS-CoV-2 on certain foods highlight the importance of safe food handling practices in mitigating any public health concerns related to potentially contaminated foods.

Objective: Burst spinal cord stimulation (B-SCS) has been shown to reduce neuronal firing in the anterior cingulate cortex through selective modulation of the medial pain pathway tract. This pain pathway communicates the affective component of pain processing. The purpose of this study was to assess the effect of B-SCS on psychosocial functioning and its influence on pain and quality of life., Materials and Methods: Eligible patients with chronic, intractable pain of the trunk, and/or lower limbs were enrolled. After a successful trial period, subjects received a permanent implant and returned for follow-up at 6- and 12-months., Results: In total, 269 patients were enrolled at 22 centers. Trial success rate was 90%. Significant improvements in pain, physical, mental, and emotional functioning were observed from baseline to the 6- and 12-month follow-up (p < 0.001). Overall, patients had improved quality of life, became more active, and the negative impact of pain on daily life was decreasing. At one year, 81% of subjects were satisfied or very satisfied with their therapy. Subjects showing significant improvements on mental health outcomes reported enhanced pain relief and quality of life scores compared with subjects with continued impaired mental health at follow-up. At one year, 89% of subjects who were taking opioids at baseline decreased or stayed at the same level of opioid use; 19% stopped taking any opioids. No unanticipated adverse events have been reported., Conclusions: One-year outcomes after B-SCS show improvements across all evaluated psychological measures with the largest impact observed on catastrophizing and depression (the affective component of pain processing). These pain-related beliefs and behaviors, and not pain intensity, have been shown to put patients at greatest risk of a poor prognosis and quality of life., (© 2020 The Authors. Neuromodulation: Technology at the Neural Interface published by Wiley Periodicals LLC. on behalf of International Neuromodulation Society.)

Background: Pharmacokinetic studies and therapeutic drug monitoring of anticoagulants require a simple, rapid, and reliable analytical method for monitoring plasma concentrations. The aims of the current work were to develop and validate a liquid chromatography/tandem mass spectrometry method for the simultaneous determination of 3 direct oral anticoagulants (dabigatran, rivaroxaban, and apixaban) in human plasma that is suitable for pharmacokinetic studies and routine therapeutic drug monitoring in busy hospital laboratories., Methods: This method included a hydrolysis step to account for the active acylglucuronide metabolites of dabigatran that demonstrate an equivalent anticoagulant effect as dabigatran. After hydrolysis, a simple one-step protein precipitation was used for sample preparation. Total dabigatran (the sum of free dabigatran and the contribution from dabigatran acylglucuronides), rivaroxaban, and apixaban, and their corresponding isotopically labeled internal standards were resolved on a C18(2) column. All compounds were detected using electrospray ionization liquid chromatography/tandem mass spectrometry in the positive mode., Results: For all 3 anticoagulants, standard curves were linear over the concentration range of 1.0-1000 mcg/L (r > 0.99), bias was < ±10%, and intraday and interday coefficients of variation (imprecision) were <10%. The limit of quantification was 1.0 mcg/L. For all 3 anticoagulants and corresponding isotopically labeled internal standards, the absolute recoveries were similar and consistent, with mean values of 93%-102%. No significant matrix effects were observed., Conclusions: This method is simple, rapid, robust, and reliable and can be used to analyze the plasma concentrations of the drugs in patients on dabigatran or rivaroxaban therapy.

Study Objectives: This systematic review aimed to examine the: (1) strength of associations between prenatal sleep (ie, duration, quality, and insomnia) and psychological health (ie, depression, anxiety, and stress); and (2) moderating influence of sociodemographic characteristics (ie, maternal age, gestational age/trimester, parity, marital and socioeconomic status [SES]), body mass index (BMI), and meeting sleep recommendations., Methods: A systematic search was conducted using PubMed, PsycINFO, Web of Science, and CINHAL to identify studies with at least one sleep measure and a psychological health outcome. Effect sizes (ES) were calculated by associations between individual components of sleep and psychological health (eg, sleep quality-depression)., Results: Reviewed studies (n = 32) included 14,648 participants and yielded 219 ES. ES for anxiety/stress were combined due to insufficient data to analyze individually. Average strengths of associations for sleep duration-depression (ES = .52) and sleep duration-anxiety/stress (ES = .48), sleep quality-depression (ES = .55) and sleep quality-anxiety/stress (ES = .58), and insomnia-depression (ES = .67) ranged from medium to large. Marital status, parity, BMI, and meeting sleep recommendations moderated sleep duration-depression and sleep duration-anxiety/stress. SES, gestational age/trimester, parity, and BMI moderated sleep quality-depression and sleep quality-anxiety/stress associations., Conclusions: Poor sleep quality and depression are prevalent during pregnancy and may negatively impact maternal and fetal outcomes. Moderating effects suggest that pregnant women of different BMI status and gestational age differ in their sleep habits and depression and anxiety/stress levels. Findings highlight the need to better understand the impact of these associations on maternal-fetal outcomes to inform interventions to improve sleep and psychological health., (© 2020 American Academy of Sleep Medicine.)

Aedes aegypti is the primary vector of dengue virus (DENV), and acquires this virus from a vertebrate host during blood feeding. Previous literature has shown that vertebrate blood factors such as complement protein C5a and low-density lipoprotein (LDL) influence DENV acquisition in the mosquito. Here, we show that extracellular vesicles in cell culture medium inhibit DENV infection in mosquito cells. Specifically, extracellular vesicles enter into mosquito cells and inhibit an early stage of infection. Extracellular vesicles had no effect on virus cell attachment or entry. Instead, extracellular vesicles restricted virus membrane fusion. Extracellular vesicles only inhibited DENV infection in mosquito cells and not vertebrate cells. These data highlight a novel virus-vector-host interaction that limits virus infection in mosquito cells by restricting virus membrane fusion., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Infant-mother behavioral synchrony is thought to scaffold the development of self-regulation in the first years of life. During this time, infants' and mothers' physiological regulation may contribute to dyadic synchrony and, in infants, dyadic synchrony may support infants' physiological regulation. Because the sympathetic nervous system (SNS) and parasympathetic nervous system (PNS) serve different regulatory functions, the current study aimed to elucidate relations between infants' and mothers' SNS and PNS functioning and dyadic behavioral synchrony. Skin conductance (SC; SNS index), respiratory sinus arrhythmia (RSA; PNS index), heart period (HP; index of joint SNS and PNS arousal), and behavioral synchrony were assessed in 6-month-old infants (N = 140) and their mothers during a mild social stressor, the Face-to-Face Still-Face paradigm (Tronick, Als, Adamson, Wise, & Brazelton, 1978). Synchrony was related to infants' and mothers' PNS and to mothers' broad autonomic arousal but not to SNS-specific arousal. Higher levels of behavioral synchrony were associated with lower infant RSA but with higher mother HP and RSA at baseline and in each Face-to-Face Still-Face paradigm episode. Therefore, lower RSA infants may have required more synchronous engagement with mothers to support regulation, while higher RSA, less aroused mothers may have been particularly well-attuned to infants' emotions. Findings suggest that each individual's physiological state may contribute to the behavioral functioning of the dyad. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

In a sample of 127 mother-infant dyads, this study examined the predictive significance of mothers' physiological and observed emotional responding within distressing and nondistressing caregiving contexts at 6 months for infant attachment assessed with Fraley and Spieker's (2003) dimensional approach and the categorical approach at 12 months. Findings revealed that a lesser degree of maternal respiratory sinus arrhythmia withdrawal and higher levels of maternal neutral (vs. positive) affect within distressing (vs. nondistressing) caregiving contexts were distinctive antecedents of avoidance versus resistance assessed dimensionally (but not categorically), independent of maternal sensitivity. Discussion focuses on the usefulness of examining mothers' physiological and affective responding, considering the caregiving context, and employing the dimensional approach to attachment in identifying unique antecedents of patterns of attachment insecurity., (© 2017 The Authors. Child Development © 2017 Society for Research in Child Development, Inc.)

Background: Pharmacokinetic studies and therapeutic drug monitoring of antibiotics require a simple, rapid, and reliable analytical method for monitoring the concentrations in plasma, including unbound concentrations for highly protein-bound drugs. The aim of the current work was to develop and validate a liquid chromatography-tandem mass spectrometry method for the simultaneous determination of total and unbound concentrations of 3 widely used β-lactam antibiotics (cefalexin, cefazolin, and flucloxacillin) and the often coadministered drug probenecid in human plasma, suitable for pharmacokinetic studies and for routine use in ordinary, busy hospital laboratories., Methods: Unbound drug was separated from bound drug by ultrafiltration. A simple 1-step protein precipitation was used for sample preparation. Cefalexin, cefazolin, flucloxacillin, probenecid, and their corresponding isotopically labeled internal standards were then resolved on a C18 (2) column. All the compounds were detected using electrospray ionization in the positive mode., Results: Standard curves were linear for all compounds over the concentration range of 0.2-100 mg/L (r > 0.99) for total drug in plasma and 0.01-10 mg/L (r > 0.99) for unbound drug in plasma ultrafiltrate. For both total and unbound drugs, bias was <±10%, and intra- and interday coefficients of variation (imprecision) were <10%. The limit of quantification was 0.2 mg/L for total plasma concentrations and 0.01 mg/L for plasma ultrafiltrate concentrations of all drugs., Conclusions: The method has proven to be simple, rapid, robust, and reliable and is currently being used in clinical pharmacokinetic studies and in the routine clinical service to enhance the effective use of the β-lactam antibiotics.

Anger is a central characteristic of negative affect and is relatively stable from infancy onward. Absolute levels of anger typically peak in early childhood and diminish as children become socialized and better able to regulate emotions. From infancy to school age, however, there are also individual differences in rank-order levels of anger. For example, although decreasing in absolute levels, some children may stay the same and others may increase in rank order relative to their peers. Although change in rank order of anger over time may provide unique insight into children's social development, little is known concerning variations in developmental patterns of anger from a rank-order perspective and how these patterns are related to children's behavioral adjustment. The current study ( N = 361) used group-based trajectory analysis and identified 6 distinct patterns of parent-reported child anger by rank across 9 months to 7 years: low-stable rank, average-stable rank, average-decreasing rank, average-increasing rank, high-decreasing rank, and high-stable rank. Most children (65.1%) were in low- to average-rank groups. However, 28.2% and 6.7% of the children were in average-increasing and high-stable groups, respectively. Children in the high-stable group showed elevated levels of externalizing and internalizing problems at age 8 compared to children in the average-stable, average-decreasing, and high-decreasing groups. These findings help to clarify different patterns of anger development across childhood and how they may relate to later problem behaviors. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Retrospective studies suggest 1 in 4 girls and 1 in 6 boys will experience sexual abuse before 18 years of age, resulting in future morbidity. Successful interventions exist, however, victims are reluctant to disclose. Screening for childhood sexual abuse (CSA) may provide an opportunity to overcome this barrier, yet no current model for universal CSA screening exists. We sought to understand the perspective of key stakeholders on CSA screening through qualitative research. Eight focus groups of 7-10 participants each (n=62) were conducted from April-September 2016. Stakeholders included school nurses, school teachers, counselors and administrators, pediatric providers, and parents. The interview guide focused on reporting suspected CSA and impressions of a CSA screening tool. Sessions were audiotaped and transcribed. Researchers used qualitative content analysis to develop conceptual categories that related to CSA screening and reporting. Two research team members independently open-coded 20% of the data for interrater reliability (kappa=0.98) prior to completing the coding process. Three major categories emerged to inform CSA screening. First, early screening (e.g. kindergarten) was preferred. Confidentiality was a concern, specifically privacy in the school-setting. As CSA perpetrators are often known to the child, parental presence in the medical office was also a concern. Finally, refinement of the screening process was discussed starting with routine education on safe touch and defining "normal." Rather than direct questioning, consistent and repeated offering of opportunities to disclose CSA and identification of a trusted adult were suggested. Next steps should involve partnering with evidence-based CSA prevention programs to incorporate and evaluate the aforementioned elements., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Obesity is an established risk factor for periprosthetic joint infections after total knee arthroplasty (TKA). In obese patients, a larger dose of prophylactic vancomycin based on actual body weight is required to reach therapeutic concentrations. It is unclear how tissue concentrations are affected when intraosseous regional administration (IORA) is used in this population. This study compared tissue concentrations of low-dose vancomycin via IORA vs actual body weight-adjusted systemic intravenous (IV) dose in primary TKA., Methods: Twenty-two patients with a body mass index (BMI) >35 undergoing TKA were randomized into 2 groups. The IV group received 15 mg/kg (maximum of 2 g) of systemic IV vancomycin and the IORA group received 500 mg vancomycin into the tibia. Subcutaneous fat and bone samples were taken at regular intervals. Tissue antibiotic concentrations were measured using liquid chromatography coupled with tandem mass spectrometry. A blood sample was taken 1 to 2 hours after tourniquet deflation to measure systemic concentration., Results: The mean BMI was 41.1 in the IORA group and 40.1 in the IV systemic group. The overall mean tissue concentration in subcutaneous fat was 39.3 μg/g in the IORA group and 4.4 μg/g in the IV systemic group (P < .01). Mean tissue concentrations in bones were 34.4 μg/g in the IORA group and 6.1 μg/g in the IV systemic group (P < .01)., Conclusion: Low-dose IORA was effective in the high-BMI population group, providing tissue concentrations of vancomycin 5-9 times higher than systemic administration. IORA optimizes timing of vancomycin administration and provides high tissue antibiotic concentrations during TKA in this high-risk patient group., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: Spinal cord stimulation (SCS) for chronic intractable pain is typically delivered in pulses, classically programmed between approximately 20 and 100 Hz. Though some recent studies suggest that better pain relief is obtained, with only 10 kHz stimulation, other studies show that single-therapy trials do not always lead to permanent implantation. We evaluated SCS outcomes in subjects given trials with multiple waveforms who did not experience satisfactory trial relief with 10 kHz stimulation only., Methods: In this multicenter, open-label, real-world, observational study conducted in the United States, subjects reporting <50% pain relief with 10 kHz stimulation (i.e., failed the screening trial) received a stimulator capable of delivering multiple waveforms and/or field shapes. Pain relief and patient device preference data were collected., Results: Twenty-two subjects were analyzed. Of the 16 who failed the 10 kHz trial and had numerical rating scale, visual analog scale, or percent pain relief scores available, 63% (n = 10) reported ≥50% relief with multiple waveform SCS. Additionally, 80% of subjects with ≥50% relief using multiple waveform SCS had experienced no relief with 10 kHz SCS. Among all subjects, 68% preferred multiple waveform SCS, none preferred 10 kHz SCS, and 32% had no preference., Discussion: Subjects with failed SCS trials at 10 kHz experienced ≥50% relief after switching to a multiple waveform system. These results suggest that providing multiple waveforms during trials may overcome limitations of providing only 10 kHz stimulation. Thus, chronic pain's variable nature across patients and over time lends itself to variable treatment options., (© 2018 International Neuromodulation Society.)

The 22-amino acid (flg22) pathogen-associated molecular pattern from the flagellin of Xanthomonas citri subsp. citri has been shown to induce defense responses correlated with citrus canker resistance. Here, flg22 of 'Candidatus Liberibacter asiaticus', the putative causal agent of Huanglongbing (HLB), elicited differential defense responses that were weaker than those from Xcc-flg22, between those of the HLB-tolerant mandarin cultivar Sun Chu Sha and susceptible grapefruit cultivar Duncan. Transcriptomics was used to compare the effect of CLas-flg22 and Xcc-flg22 between the citrus genotypes and identified 86 genes induced only by CLas-flg22 in the tolerant mandarin. Expression of 16 selected genes was validated, by reverse transcription-quantitative polymerase chain reaction, and was evaluated in citrus during 'Ca. L. asiaticus' infection. Differential expression of a number of genes occurred between tolerant and susceptible citrus infected with 'Ca. L. asiaticus', suggesting their involvement in HLB tolerance. In addition, several genes were similarly regulated by CLas-flg22 and 'Ca. L. asiaticus' treatments, while others were oppositely regulated in the tolerant mandarin, suggesting similarity and interplay between CLas-flg22 and 'Ca. L. asiaticus'-triggered defenses. Genes identified are valuable in furthering the study of HLB tolerance mechanisms and, potentially, for screening for HLB-tolerant citrus using CLas-flg22 as a pathogen proxy.

Background: In primary TKA, prophylaxis with low-dose vancomycin through intraosseous regional administration (IORA) achieves tissue concentrations six to 10 times higher than systemic administration and was shown to provide more effective prophylaxis in an animal model. However, in revision TKA, the presence of a tibial implant may compromise IORA injection, and tourniquet deflation during a prolonged procedure may lower tissue concentrations., Questions/purposes: (1) Does low-dose IORA reliably provide equal or higher tissue concentrations of vancomycin compared with systemic IV administration in revision TKA? (2) Are tissue concentrations of vancomycin after IORA maintained for the duration of the revision TKA despite a period of tourniquet deflation? (3) Is there any difference in early postoperative (< 6 weeks) complications between IORA and systemic IV administration in revision TKA?, Methods: Twenty patients undergoing aseptic revision TKA were randomized to two groups. The IV group received 1 g systemic IV prophylactic vancomycin. The IORA group received 500 mg vancomycin as a bolus injection into a tibial intraosseous cannula below an inflated thigh tourniquet before skin incision. In all patients receiving IORA, intraosseous tibial injection was technically possible despite the presence of a tibial implant. Mean procedure length was 3.5 hours in both groups. Mean initial tourniquet inflation was 1.5 hours with a second inflation for a mean of 35 minutes during cementation. During the procedure, subcutaneous fat and bone samples were taken at regular intervals. Tissue vancomycin concentrations were measured using high-performance liquid chromatography., Results: Overall geometric mean tissue concentration of vancomycin in fat samples was 3.7 μg/g (95% confidence interval [CI], 2.6-5.2) in the IV group versus 49.3 μg/g in the IORA group (95% CI, 33.2-73.4; ratio between means 13.5; 95% CI, 8.2-22.0; p < 0.001); mean tissue concentrations in femoral bone were 6.4 μg/g (95% CI, 4.5-9.2) in the IV group versus 77.1 μg/g (95% CI, 42.4-140) in the IORA group (ratio between means 12.0; 95% CI, 6.2-23.2; p < 0.001). Vancomycin concentrations in the final subcutaneous fat sample taken before closure were 5.3 times higher in the IORA group versus the IV group (mean ± SD, 18.2 ± 11.6 μg/g IORA versus 3.6 ± 2.5 μg/g; p < 0.001). The intraarticular concentration of vancomycin on postoperative Day 1 drain samples was not different between the two groups with the numbers available (mean 4.6 μg/L in the IV group versus 6.6 μg/g in the IORA group; mean difference 2.0 μg/g; 95% CI, 6.2-23.2; p = 0.08)., Conclusions: IORA administration of vancomycin in patients undergoing revision TKA resulted in tissue concentrations of vancomycin five to 20 times higher than systemic IV administration despite the lower dose. High tissue concentrations were maintained throughout the procedure despite a period of tourniquet deflation. These preliminary results justify prospective cohort studies, which might focus on broader safety endpoints in more diverse patient populations. We believe that these studies should evaluate patients undergoing revision TKA in particular, because the risk of infection is greater than in patients undergoing primary TKA., Level of Evidence: Level I, therapeutic study.

Purpose: Marital dissatisfaction and conflict often increase for couples after the birth of a child and are evident in fewer positive family interactions and more negative family interactions. Because exercise is known to increase positive emotions and decrease negative emotions, the current study examined the extent to which higher levels of mothers' exercise during the postpartum period were related to more positive and fewer negative emotion-expressive behaviors with their infants' fathers., Method: Mothers' (N = 46; M = 8 months postpartum) positive and negative expressive behaviors were coded during couples' discussions of current conflict and positive family experiences. Mothers self-reported their leisure-time exercise behavior., Results: First-time mothers and mothers with higher levels of leisure-time exercise behavior displayed higher levels of positive expressive behaviors during couples' discussions., Conclusions: Exercise may be associated with increased positive emotion and, in turn, can have great potential to improve family relationships during the postpartum period when marital stress normatively increases, particularly for mothers with more than 1 child. Future longitudinal studies are needed to understand exercise patterns across the postpartum period to identify the most effective timing and optimal level of exercise that lead to more positive expressive behaviors.

Xanthomonas citri ssp. citri (X. citri), causal agent of citrus canker, uses transcription activator-like effectors (TALEs) as major pathogenicity factors. TALEs, which are delivered into plant cells through the type III secretion system (T3SS), interact with effector binding elements (EBEs) in host genomes to activate the expression of downstream susceptibility genes to promote disease. Predictably, TALEs bind EBEs in host promoters via known combinations of TALE amino acids to DNA bases, known as the TALE code. We introduced 14 EBEs, matching distinct X. citri TALEs, into the promoter of the pepper Bs3 gene (ProBs3 1EBE ), and fused this engineered promoter with multiple EBEs (ProBs3 14EBE ) to either the β-glucuronidase (GUS) reporter gene or the coding sequence (cds) of the pepper gene, Bs3. TALE-induced expression of the Bs3 cds in citrus leaves resulted in no visible hypersensitive response (HR). Therefore, we utilized a different approach in which ProBs3 1EBE and ProBs3 14EBE were fused to the Xanthomonas gene, avrGf1, which encodes a bacterial effector that elicits an HR in grapefruit and sweet orange. We demonstrated, in transient assays, that activation of ProBs3 14EBE by X. citri TALEs is T3SS dependent, and that the expression of AvrGf1 triggers HR and correlates with reduced bacterial growth. We further demonstrated that all tested virulent X. citri strains from diverse geographical locations activate ProBs3 14EBE . TALEs are essential for the virulence of X. citri strains and, because the engineered promoter traps are activated by multiple TALEs, this concept has the potential to confer broad-spectrum, durable resistance to citrus canker in stably transformed plants., (© 2016 BSPP AND JOHN WILEY & SONS LTD.)

Background: In citrus the transition from juvenility to mature phase is marked by the capability of a tree to flower and fruit consistently. The long period of juvenility in citrus severely impedes the use of genetic based strategies to improve fruit quality, disease resistance, and responses to abiotic environmental factors. One of the genes whose expression signals flower development in many plant species is FLOWERING LOCUS T (FT)., Results: In this study, gene expression levels of flowering genes CiFT1, CiFT2 and CiFT3 were determined using reverse-transcription quantitative real-time PCR in citrus trees over a 1 year period in Florida. Distinct genotypes of citrus trees of different ages were used. In mature trees of pummelo (Citrus grandis Osbeck) and 'Pineapple' sweet orange (Citrus sinensis (L.) Osbeck) the expression of all three CiFT genes was coordinated and significantly higher in April, after flowering was over, regardless of whether they were in the greenhouse or in the field. Interestingly, immature 'Pineapple' seedlings showed significantly high levels of CiFT3 expression in April and June, while CiFT1 and CiFT2 were highest in June, and hence their expression induction was not simultaneous as in mature plants., Conclusions: In mature citrus trees the induction of CiFTs expression in leaves occurs at the end of spring and after flowering has taken place suggesting it is not associated with dormancy interruption and further flower bud development but is probably involved with shoot apex differentiation and flower bud determination. CiFTs were also seasonally induced in immature seedlings, indicating that additional factors must be suppressing flowering induction and their expression has other functions.

Children exposed to parent conflict may be at risk for emotional and behavioral disorders by becoming sensitized to conflict cues in their environments. This study explored possible precursors to negative child outcomes associated with parent conflict by examining the relation between parent conflict and infants' (N = 36; 23-42 weeks; 44% female) behavioral sensitivity to general sensory stimuli (e.g., loud noises, physical touch). To determine whether infants' characteristic autonomic arousal and regulation moderated this association, infant baseline skin conductance (SC) and respiratory sinus arrhythmia (RSA) were measured. Parents reported levels of parent conflict, and mothers reported infants' behavioral sensory sensitivity. The association between parent conflict and lower threshold for sensory sensitivity was strongest for infants with higher physiological arousal (higher SC) and lesser capacity for physiological regulation (lower RSA). Children may become more sensitive to environmental stimuli as a function of parent conflict during infancy, though this appears to depend on characteristic physiological arousal and regulation., (© 2017 Wiley Periodicals, Inc.)

Parent conflict is related to attenuated infant vagal reactivity, suggesting less effective regulation. Because infants' self-regulation develops in the context of coregulation, the current study examined a novel measure, flexibility, purported to reflect dyadic reorganization in response to contextual demands. Flexibility was expected to mediate the relation between greater conflict and lesser vagal reactivity during the reunion episode of the Face-to-Face Still-Face (FFSF). Six-month-old infants' and their mothers' (N = 53) affective behaviors were observed during the FFSF and heart rate data were collected for infants. Flexibility was computed using state-space analysis of dyadic behaviors and measured variability in and movement among dyadic states. Conflict was related to lesser infant vagal reactivity in the reunion through lower flexibility, suggesting less effective recovery from social stress. Flexibility may capture aspects of coregulation affected by environmental stress and may be one mechanism by which conflict contributes to developing vagal regulation., (© 2017 Wiley Periodicals, Inc.)

Consistent with the gustatory-vagal hypothesis, vagal stimulation during breastfeeding may contribute to infants' physiological regulatory development independent of caregiving effects. This study examined whether breastfeeding predicted 6-month-old infants' (N = 151) and their mothers' vagal regulation during the face-to-face still-face (FFSF). Although breastfed and nonbreastfed infants showed expected vagal withdrawal during the Still-Face episode, only breastfed infants showed continued withdrawal during the reunion episode, suggesting greater physiological mobilization to repair the interaction. Breastfeeding mothers showed higher vagal tone than nonbreastfeeding mothers at baseline, suggesting greater capacity for regulation, and throughout the FFSF, suggesting calmer states. Breastfeeding effects were independent of maternal sensitivity. Findings suggest that infants' and mothers' physiological regulation may be shaped by breastfeeding independently of associated social factors., (© 2016 The Authors. Child Development © 2016 Society for Research in Child Development, Inc.)

This study investigated the interaction between children's parasympathetic functioning and maternal sensitive parenting behaviors during infancy and toddlerhood in the prediction of children's executive functions (EF) at the age of 5 years. Participants included 137 children and their mothers who were followed from the age of 3 months to 5 years. Children's cardiac activity was recorded at rest at multiple times from ages 3 to 36 months, and estimates of respiratory sinus arrhythmia (RSA; a measure of parasympathetic functioning) were calculated. Sensitive parenting was assessed during a mother-child play task at ages 6, 12, 24, and 36 months, and 5 years. Children completed age appropriate EF tasks at the age of 5 years. The link between sensitive parenting during toddlerhood (ages 24 and 36 months) and children's later EF was moderated by children's RSA such that this positive link was evident only among children who had low levels of baseline RSA, and not among those who had high levels of baseline RSA. These findings were obtained while controlling for concurrent sensitive parenting and maternal and child verbal abilities. Results from this study provide evidence for the significant role of biopsychosocial processes in early childhood in the development of EF., (Copyright © International Congress of Infant Studies (ICIS).)

This study examined the direct and interactive effects of infants' respiratory sinus arrhythmia (RSA) and maternal depressive symptoms (MDS) during the first 6 months of life in the prediction of children's sleep problems at age 18 months. Participants included 156 children and their mothers who were followed from 3 to 18 months of age. At ages 3 and 6 months, infants' cardiac activity was recorded at rest and during the still-face paradigm, a mother-child social challenge task, and estimates of infant baseline RSA (RSAB) and RSA withdrawal (RSAW) were calculated. Mothers reported about their depressive symptoms at 3, 6, and 18 months, and about infants' sleep problems at age 18 months. Less RSAW and higher levels of MDS predicted more sleep problems at age 18 months. Additionally, RSAB moderated the link between MDS and children's sleep problems such that MDS were related to more sleep problems only for infants with high levels of RSAB. Results illustrate the importance of RSA as both a direct predictor and a moderator of maternal influences in the prediction of early sleep problems., (© 2016 Wiley Periodicals, Inc.)

Achieving sustainable management of phosphorus (P) is crucial for both global food security and global environmental protection. In order to formulate informed policy measures to overcome existing barriers of achieving sustainable P management, there is need for a sound understanding of the nature and magnitude of P flow through various systems at different geographical and temporal scales. So far, there is a limited understanding on the nature and magnitude of P flow over multiple years at the regional scale. In this study, we have developed a novel substance flow analysis (SFA) model in the MATLAB/Simulink® software platform that can be effectively utilized to analyse the nature and magnitude of multi-year P flow at the regional scale. The model is inclusive of all P flows and storage relating to all key systems, subsystems, processes or components, and the associated interactions of P flow required to represent a typical P flow system at the regional scale. In an annual time step, this model can analyse P flow and storage over as many as years required at a time, and therefore, can indicate the trends and changes in P flow and storage over many years, which is not offered by the existing regional scale SFA models of P. The model is flexible enough to allow any modification or the inclusion of any degree of complexity, and therefore, can be utilized for analysing P flow in any region around the world. The application of the model in the case of Gippsland region, Australia has revealed that the model generates essential information about the nature and magnitude of P flow at the regional scale which can be utilized for making improved management decisions towards attaining P sustainability. A systematic reliability check on the findings of model application also indicates that the model produces reliable results., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Deficits in social orienting (i.e., gazing toward caregivers) during dyadic interactions and reactivity to stressful stimuli have been identified as behavioral correlates of oppositional defiant disorder (ODD) and callous-unemotional (CU) behaviors in older children. The goal of the current study was to investigate infants' mother-directed gaze and reactivity during the face-to-face and still-face episodes of the face-to-face stillface paradigm performed at 6 months in the prediction of ODD and CU behaviors in early childhood. Using data from the Durham Child Health and Development study (n = 206), hierarchical regression analyses revealed that infants' negative reactivity during the still-face episode and mother-directed gaze during the face-to-face episode predicted fewer ODD behaviors in early childhood. Examination of interaction effects suggested that mother-directed gaze attenuated the negative relation between reactivity and ODD and CU behaviors in early childhood. The current study is one of the first to extend downward the investigation of ODD and CU behaviors into infancy.

Touch is the primary modality infants use to engage with the world; atypical responses to tactile stimuli may indicate risk for disordered outcomes. The current study examined infants' responses to tactile stimulation within parent-child interaction, adding to prior knowledge based on parent report. Nine-month-old infants (N=497) were observed while parents painted and pressed infants' hands and feet to paper to make designs. Positive and negative affect and gazing away, exploring, and resistance behaviors were coded. Latent Class Analysis of observed behaviors yielded four tactile response patterns partially consistent with current nosology for sensory processing patterns: Low Reactive, Sensory Overreactive, Sensory Seeking, and Mixed Over/Underreactive. To evaluate whether patterns made valid distinctions among infants, latent classes were examined in relation to parent-reported temperament. Infants in the Mixed Over/Underreactive class were rated higher in distress to limitations and activity level than other infants. Sensory processing patterns observed in parent-child interaction are consistent with those identified by parent-report and may be used in future research to elucidate relations with temperament and typical and atypical development., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Pathogen-associated molecular patterns (PAMPs)-triggered immunity (PTI) is an important component of plant innate immunity. In a previous study, we showed that the PAMP flg22 from Xanthomonas citri ssp. citri (Xflg22), the causal agent of citrus canker, induced PTI in citrus, which correlated with the observed levels of canker resistance. Here, we identified and sequenced two bacterial flagellin/flg22 receptors (FLS2-1 and FLS2-2) from 'Duncan' grapefruit (Citrus paradisi, CpFLS2-1 and CpFLS2-2) and 'Sun Chu Sha' mandarin (C. reticulata, CrFLS2-1 and CrFLS2-2). We were able to isolate only one FLS2 from 'Nagami' kumquat (Fortunella margarita, FmFLS2-1) and gene flanking sequences suggest a rearrangement event that resulted in the deletion of FLS2-2 from the genome. Phylogenetic analysis, gene structure and presence of critical amino acid domains all indicate we identified the true FLS2 genes in citrus. FLS2-2 was more transcriptionally responsive to Xflg22 than FLS2-1, with induced expression levels higher in canker-resistant citrus than in susceptible ones. Interestingly, 'Nagami' kumquat showed the highest FLS2-1 steady-state expression levels, although it was not induced by Xflg22. We selected FmFLS2-1, CrFLS2-2 and CpFLS2-2 to further evaluate their capacity to enhance bacterial resistance using Agrobacterium-mediated transient expression assays. Both FmFLS2-1 and CrFLS2-2, the two proteins from canker-resistant species, conferred stronger Xflg22 responses and reduced canker symptoms in leaves of the susceptible grapefruit genotype. These two citrus genes will be useful resources to enhance PTI and achieve resistance against canker and possibly other bacterial pathogens in susceptible citrus types.

Maternal positivity and mother-infant synchrony have been linked, independently, to beneficial infant outcomes; however, research that has examined relations between the two has found that higher positivity is associated with lower synchrony. Methodological issues may inform this counter-intuitive association and clinical theory supports its validity. This study examined the theory that heightened positivity associated with anxiety is a way of avoiding negative emotion and contributes to lower synchrony because it interferes with appropriate responding to infant cues. We examined mothers' (N=75) self-reported anxiety and verbal expression of positivity during pregnancy in relation to mother-infant synchrony at 6 months post-partum. Verbal positivity was assessed using linguistic analysis of interviews about pregnancy experiences. Mother and infant affect and gaze were coded during interaction and synchrony was computed as the correlation between mother and infant behaviors. Higher verbal positivity and anxiety during pregnancy independently predicted lower mother-infant synchrony, suggesting distinct pathways to the same degree of synchrony with potentially different consequences for infant development., (Copyright © 2015 Elsevier Inc. All rights reserved.)

The experience of touch is critical for early communication and social interaction; infants who show aversion to touch may be at risk for atypical development and behavior problems. The current study aimed to clarify predictive associations between infant responses to tactile stimuli and toddler autism spectrum, internalizing, and externalizing behaviors. This study measured 9-month-old infants' (N = 561; 58% male) avoidance and negative affect during a novel tactile task in which parents painted infants' hands and feet and pressed them to paper to make a picture. Parent reports on the Pervasive Developmental Problems (PDP), Internalizing, and Externalizing scales of the Child Behavior Checklist were used to measure toddler behaviors at 18 months. Infant observed avoidance and negative affect were significantly correlated; however, avoidance predicted subsequent PDP scores only, independent of negative affect, which did not predict any toddler behaviors. Findings suggest that incorporating measures of responses to touch in the study of early social interaction may provide an important and discriminating construct for identifying children at greater risk for social impairments related to autism spectrum behaviors., (© 2015 Michigan Association for Infant Mental Health.)

This study used a data-driven, person-centered approach to examine the characterization, continuity, and etiology of child temperament from infancy to toddlerhood. Data from 561 families who participated in an ongoing prospective adoption study, the Early Growth and Development Study, were used to estimate latent profiles of temperament at 9, 18, and 27 months. Results indicated that four profiles of temperament best fit the data at all three points of assessment. The characterization of profiles was stable over time, while membership in profiles changed across age. Facets of adoptive parent and birth mother personality were predictive of children's profile membership at each age, providing preliminary evidence for specific environmental and genetic influences on patterns of temperament development from infancy to toddlerhood., (© 2015 The Authors. Child Development © 2015 Society for Research in Child Development, Inc.)

Objective: To determine whether baseline dimensions of adult insecure attachment (avoidant and anxious) moderated outcome in a secondary analysis of a randomized controlled trial comparing cognitive-behavioral therapy (CBT) plus supportive listening (CBT + SL) versus CBT plus interpersonal and emotional processing therapy (CBT + I/EP)., Method: Eighty-three participants diagnosed with generalized anxiety disorder (GAD) were recruited from the community and assigned randomly to CBT + SL (n = 40) or to CBT + I/EP (n = 43) within a study using an additive design. PhD-level psychologists treated participants. Blind assessors evaluated participants at pretreatment, posttreatment, 6-month, 12-month, and 2-year follow-up with a composite of self-report and assessor-rated GAD symptom measures (Penn State Worry Questionnaire, Hamilton Anxiety Rating Scale, Clinician's Severity Rating). Avoidant and anxious attachment were assessed using self-reported dismissing and angry states of mind, respectively, on the Perceptions of Adult Attachment Questionnaire., Results: Consistent with our prediction, at all assessments higher levels of dismissing styles in those who received CBT + I/EP predicted greater change in GAD symptoms compared with those who received CBT + SL for whom dismissiveness was unrelated to the change. At postassessment, higher angry attachment was associated with less change in GAD symptoms for those receiving CBT + I/EP, compared with CBT + SL, for whom anger was unrelated to change in GAD symptoms. Pretreatment attachment-related anger failed to moderate outcome at other time points and therefore, these moderation effects were more short-lived than the ones for dismissing attachment., Conclusions: When compared with CBT + SL, CBT + I/EP may be better for individuals with GAD who have relatively higher dismissing styles of attachment., ((c) 2015 APA, all rights reserved).)

The bacterial agent of citrus canker disease (Xanthomonas citri ssp. citri, Xcc) has caused tremendous economic losses to the citrus industry around the world. Pathogen-associated molecular pattern (PAMP)-triggered immunity (PTI) is important to plant immunity. In this study, we compared the defence responses of citrus canker-resistant and citrus canker-susceptible genotypes to the Xcc-derived PAMP flg22 (Xflg22) by analysing the expression of 20 citrus defence-associated genes. We showed that, in the most resistant genotype, 'Nagami' kumquat, there was significant induction of several defence genes (EDS1, NDR1, PBS1, RAR1, SGT1, PAL1, NPR2 and NPR3) as early as 6 h and up to 72 h after Xflg22 treatment. At the other end of the spectrum, highly susceptible 'Duncan' grapefruit showed no induction of the same defence genes, even 120 h after treatment. Citrus genotypes with partial levels of resistance showed intermediate levels of transcriptional reprogramming that correlated with their resistance level. Xflg22 also triggered a rapid oxidative burst in all genotypes which was higher and accompanied by the induction of PTI marker genes (WRKY22 and GST1) only in the more resistant genotypes. Pretreatment with Xflg22 prior to Xcc inoculation inhibited bacterial growth in kumquat, but not in grapefruit. A flagellin-deficient Xcc strain (XccΔfliC) showed greater growth increase relative to wild-type Xcc in kumquat than in grapefruit. Taken together, our results indicate that Xflg22 initiates strong PTI in canker-resistant genotypes, but not in susceptible ones, and that a robust induction of PTI is an important component of citrus resistance to canker., (© 2014 BSPP AND JOHN WILEY & SONS LTD.)

Transactional models of analysis can examine both moment-to-moment interactions within a dyad and dyadic patterns of influence across time. This study used data from a prospective adoption study to test a transactional model of parental depressive symptoms and mutual negativity between mother and child over time, utilizing contingency analysis of second-by-second behavioral data. To consider both genetic and environmental influences on mutual negativity, depressive symptoms were examined in both adoptive and birth mothers. Adoptive mother depressive symptoms at 9 months increased the likelihood that, at 18 months, children reacted negatively to their mothers' negative behavior, which in turn predicted higher levels of adoptive mother depressive symptoms at 27 months, suggesting that over time, mothers' depressive symptoms influence and are influenced by moment-to-moment mutual negativity with their toddlers. Birth mother depressive symptoms moderated the association between mutual negativity at 18 months and adoptive mother depressive symptoms at 27 months, suggesting a child-driven contribution to maternal depressive symptoms that can be measured by a genetic sensitivity.

We report the synthesis and characterization of pH-responsive polysuccinimide-based nanoparticles. Polysuccinimide (PSI), a precursor to biodegradable poly(aspartic acid), was synthesized from the condensation of l-aspartic acid and subsequently functionalized with primary amines to form random amphiphilic copolymers. The copolymers formed stable nanoparticles in aqueous medium via nanoprecipitation and were subsequently loaded with a model hydrophobic molecule to demonstrate their potential as controlled-release delivery vehicles. It was found that above pH 7, the hydrophobic succinimidyl units of the PSI nanoparticles hydrolyzed to release encapsulated materials. The release rate significantly increased at elevated pH and decreased with an increasing degree of functionalization. Finally, plant toxicity studies showed that the polymer materials exhibit little to no toxic effects at biologically relevant concentrations.

The authors investigated the relationships among parenting behaviors, infant vagal tone, and subsequent attachment classification. Vagal tone was assessed among 6-month olds (n = 95) during the still-face paradigm (SFP) via respiratory sinus arrhythmia (RSA), while attachment security and disorganization were measured at 12 months during the strange situation procedure (SSP). Infants demonstrating higher levels of RSA during the normal interaction and reunion episodes of the SFP whose mothers were also rated as negative-intrusive exhibited higher levels of attachment disorganization at 12 months, while infants with lower RSA and mothers who were negative-intrusive did not exhibit higher levels of disorganization. These results suggest that high levels of RSA may not be adaptive within the context of negative-intrusive parenting., (© 2014 Wiley Periodicals, Inc.)

Family theories have been founded on research that cannot discriminate genetic and environmental influences and, consequently, most theories do not have highly developed models of gene-environment interplay in families. Behavioral genetic approaches, which can identify gene-environment interplay, have typically not been driven by family theories and have lacked adequate measurement of family processes. In this article, the authors describe behavioral genetic mechanisms and methods using representative examples of research on family processes, highlighting the advantages of an integrated approach. New directions in research and theory driven by an integrated approach are discussed.

Background: A busulfan concentration monitoring and dosing service has been provided by Christchurch Hospital since 1998. This study aimed to see (1) the percentage of patients with an area under the concentration time curve (AUC) outside the target range and had dose adjustment, (2) how busulfan clearance (CL) relates to body weight, and (3) if fewer samples could be used to predict doses., Methods: Blood samples were taken from patients after oral administration, usually at 0.5, 1, 1.5, and 6 hours, and after the start of a 2-hour intravenous (IV) infusion of busulfan, at 1, 2, 2.5, 3, 6, and 8 hours. Dose adjustment was made based on the AUC compared with the target range. The relationship of CL and body weight for the IV group was used to develop a revised IV dosing schedule. The bias and imprecision of AUCs estimated using fewer sampling points were examined to see if sampling could be economized., Results: Data were available for 150 patients but for 6 patients, data were incomplete and excluded. Of the remaining 144 patients (256 sample sets, 209 oral, 47 IV, 62% with repeats), 38% (IV) and 35% (oral) of patients had AUCs within the target range after the first dose. Dose adjustment was made in 47% and 34% of patients dosed IV and orally, respectively, after which there was a trend to more patients achieving the target AUC. A nonlinear relationship was found between CL and body weight. The initial IV dosing schedule was revised to take this into account. Sampling for busulfan concentration measurement at 3 points (2.5, 4, 8 hours) or 2 points (2.5, 8 hours) after the start of the infusion enabled accurate and precise estimates of AUC₀₋₂₄., Conclusions: Around two thirds of patients treated with busulfan were outside the target AUC range after the first dose. Dose adjustment was made in 37% of patients. The relationship between CL and body weight was used to revise the initial IV dosing schedule. Sampling for AUC estimation could be reduced to 2 time points after IV dosing.

Background: In response to increasing antibiotic resistance, vancomycin has been proposed as an alternative prophylactic agent in TKA. However, vancomycin requires a prolonged administration time, risks promoting further antibiotic resistance, and can cause systemic toxicity. Intraosseous regional administration (IORA) is known to achieve markedly higher antibiotic concentrations than systemic administration and may allow the use of a lower vancomycin dose., Questions/purposes: We assessed whether low-dose IORA vancomycin can achieve tissue concentrations equal or superior to those of systemic administration in TKA and compared complications between patients treated with IORA and intravenous vancomycin., Methods: We randomized 30 patients undergoing primary TKA to receive 250 or 500 mg vancomycin via IORA or 1 g via systemic administration. IORA was performed as a bolus injection into a tibial intraosseous cannula below an inflated thigh tourniquet immediately before skin incision. Subcutaneous fat and bone samples were taken during the procedure and antibiotic concentrations measured., Results: The overall mean tissue concentration of vancomycin in subcutaneous fat was 14 μg/g in the 250-mg IORA group, 44 μg/g in the 500-mg IORA group, and 3.2 μg/g in the systemic group. Mean concentrations in bone were 16 μg/g in the 250-mg IORA group, 38 μg/g in the 500-mg IORA group, and 4.0 μg/g in the systemic group. One patient in the systemic group developed red man syndrome during infusion., Conclusions: Low-dose IORA vancomycin results in tissue concentrations equal or superior to those of systemic administration. IORA optimizes timing of vancomycin administration, and the lower dose may reduce the risk of systemic side effects while providing equal or enhanced prophylaxis in TKA.

Consumption of energy drinks by both recreational and competitive athletes has increased dramatically in recent years. The primary ingredients in many energy drinks include caffeine (CAF) in various forms and taurine. The purpose of this randomized, double-blind, crossover study was to examine the effect of sugar-free (SF) Red Bull (RB) containing CAF and taurine to a CAF only drink and a SF CAF-free placebo (PL) on 1 repetition maximum (1RM) bench press (BP) and the volume load (VL; repetitions × kg at 70% 1RM) during one BP set to failure in experienced lifters. Seventeen college-age men randomly received the following: (A) 500 mL of SF-RB containing CAF (160 mg) and taurine (2000 mg); (B) 500 mL of a SF drink containing CAF only (160 mg); or (C) a SF CAF-free 500 mL PL drink 60 minutes before testing on 3 separate occasions. After a standard warm-up, the 1RM was determined for each subject and, after 5 minutes rest, they completed repetitions to failure at 70% of their 1RM to assess VL. Differences between trials for 1RM BP and the VL were identified using repeated measures analysis of variance (p < 0.05). The results indicated that neither SF-RB nor the CAF drink had any effect on 1RM BP (115.13 ± 16.19 kg and 114.87 ± 16.16 kg, respectively) or VL (1173.08 ± 170.66 kg and 1164.14 ± 147.03 kg, respectively) compared with PL (1RM = 114.07 ± 16.09 kg; VL = 1141.46 ± 193.41 kg). Although the CAF content in the energy drinks used in the present study was low (∼2.0 mg/kg), the finding of no effect of the CAF containing energy drinks for 1RM BP are in agreement with previous studies using intakes up to 6.0 mg/kg. These findings suggest that SF-RB has no effect on upper body 1RM strength or VL in resistance trained men.

A recent increase in the incidence of diabetes and pre-diabetes is causing many employers to spend more of their healthcare benefit budgets to manage the conditions. A self-insured university in the USA has implemented an interprofessional diabetes mellitus risk reduction program using its own employee faculty and staff experts to help fellow employees manage their diabetes and pre-diabetes. The interprofessional team consists of five pharmacists, a dietitian, an exercise physiologist, a health educator and a licensed mental health practitioner. In addition, the participant's physician serves as a consultant to the program, as does a human resources healthcare benefits specialist and a wellness coordinator. The volunteer program takes place at the worksite during regular business hours and is free of charge to the employees. The faculty and staff delivering the program justify the cost of their time through an interprofessional educational model that the program will soon provide to university students.

The study of dyadic interaction plays a major role in infancy research. To advance conceptually-informed measurement of dyadic interaction and integration across studies, we examined factor structure of individual parents' and infants' measures and dyadic measures from face-to-face interactions in two samples of 6-mo-old infants and their parents: mothers from a demographically heterogeneous sample ( N = 164) and mothers and fathers ( N = 156) from a Caucasian middle-class sample. Results suggested: a) individual and dyadic measures, and parents' and infants' behaviors contribute independent information, b) measures of both valence and process are needed, c) there are context-general and context-specific qualities, and d) structure of dyadic interaction is more similar among mother-infant dyads from independent samples than between mother- and father-infant dyads within the same sample. Future research should use multiple measures incorporating valence, temporal processes, contextual influences, and behaviors of individual partners along with dyadic measures to adequately assess the quality of dyadic interaction.

A rapid and simple high-performance liquid chromatography (HPLC) assay was developed for the simultaneous determination of three triazole antifungals (voriconazole, posaconazole, and itraconazole and the metabolite of itraconazole, hydroxyitraconazole) in human plasma. Sample preparation involved a simple one-step protein precipitation with 1.0 M perchloric acid and methanol. After centrifugation, the supernatant was injected directly into the HPLC system. Voriconazole, posaconazole, itraconazole, its metabolite hydroxyitraconazole, and the internal standard naproxen were resolved on a C(6)-phenyl column using gradient elution of 0.01 M phosphate buffer, pH 3.5, and acetonitrile and detected with UV detection at 262 nm. Standard curves were linear over the concentration range of 0.05 to 10 mg/liter (r(2) > 0.99). Bias was <8.0% from 0.05 to 10 mg/liter, intra- and interday coefficients of variation (imprecision) were <10%, and the limit of quantification was 0.05 mg/liter.

Although there are no known sources of genetic resistance, some Citrus spp. are reportedly tolerant to huanglongbing (HLB), presumably caused by 'Candidatus Liberibacter asiaticus'. Time-course transcriptional analysis of tolerant rough lemon (Citrus jambhiri) and susceptible sweet orange (C. sinensis) in response to 'Ca. L. asiaticus' infection showed more genes differentially expressed in HLB-affected rough lemon than sweet orange at early stages but substantially fewer at late time points, possibly a critical factor underlying differences in sensitivity to 'Ca. L. asiaticus'. Pathway analysis revealed that stress responses were distinctively modulated in rough lemon and sweet orange. Although microscopic changes (e.g., callose deposition in sieve elements and phloem cell collapse) were found in both infected species, remarkably, phloem transport activity in midribs of source leaves in rough lemon was much less affected by HLB than in sweet orange. The difference in phloem cell transport activities is also implicated in the differential sensitivity to HLB between the two species. The results potentially lead to identification of key genes and the genetic mechanism in rough lemon to restrain disease development and maintain (or recover) phloem transport activity. These potential candidate genes may be used for improving citrus tolerance (or even resistance) to HLB by genetic engineering.

Imatinib is a first-line treatment for chronic myelogenous leukaemia (CML). The pharmacokinetics of imatinib in patients with CML are characterised by large interpatient variability. Concentration monitoring of imatinib and its active metabolite N-desmethyl imatinib (DMI) is considered necessary to enhance the safe and effective use of imatinib. A rapid, simple and sensitive liquid chromatography/tandem mass spectrometry assay was developed for the simultaneous determination of imatinib and its metabolite DMI in human plasma. After proteins were precipitated with acetonitrile, imatinib, DMI and the internal standard D8-imatinib were resolved on a Gemini-NX 3 μm C18 column using gradient elution of 0.05 % formic acid and methanol. The three compounds were detected using electrospray ionisation in the positive mode. Standard curves of imatinib and DMI were adequately fitted by quadratic equations (r > 0.999) over the concentration range of 10 to 2,000 ng/mL which encompasses clinical concentrations. Bias was ≤±8.3 %, intra- and inter-day coefficients of variation (imprecision) were ≤8.0 % and the limit of quantification was 10 ng/mL for both imatinib and DMI. The assay is being used successfully in clinical practice to enhance the safe and effective use of imatinib.

Infants' emerging ability to move independently by crawling is associated with changes in multiple domains, including an increase in expressions of anger in situations that block infants' goals, but it is unknown whether increased anger is specifically because of experience with being able to move autonomously or simply related to age. To examine the influence of locomotion on developmental change in anger, infants' (N = 20) anger expressions during an arm restraint procedure were observed longitudinally at a precrawling baseline assessment and 2 and 6 weeks after the onset of crawling. Infant age at each crawling stage was unrelated to the frequency of anger expressed in response to arm restraint. At 6 weeks postcrawling onset, infants whose mothers rated them as temperamentally higher in distress to limitations, compared with those rated lower, showed a greater increase in the frequency of anger expressed during the arm restraint relative to earlier assessments and took longer to reduce the frequency of anger expressed when no longer restrained. Findings suggest that experience with autonomous crawling has an effect on anger expression, independent of age, and that a temperamental tendency to become distressed by limitations may exacerbate the effect of crawling on anger expression., (Copyright © International Society on Infant Studies (ISIS).)

The onset of depressive symptoms during pregnancy or the first year postpartum, termed perinatal depression, occurs in approximately 15 percent of women. Perinatal depression can have a significant negative impact on health outcomes for the mother and her infant including maternal emotional distress and parenting difficulties and infant behavioral and developmental problems. Nurses caring for patients in the neonatal intensive care unit (NICU) are in a key position to affect positive change in the lives of families affected by perinatal depression. An overview of antepartum and postpartum depression is provided that has been tailored to the educational needs of the neonatal nurse. A discussion of the role of neonatal nurses in the identification and treatment of perinatal depression follows in order that neonatal nurses may improve both short- and long-term outcomes for mothers, infants, and families in the NICU affected by perinatal depression.

In the present study, the full-length cDNA sequences of PSY, PDS, and ZDS, encoding the early carotenoid biosynthetic enzymes in the carotenoid pathway of grapefruit (Citrus paradisi), were isolated and characterized for the first time. CpPSY contained a 1311-bp open reading frame (ORF) encoding a polypeptide of 436 amino acids, CpPDS contained a 1659-bp ORF encoding a polypeptide of 552 amino acids, and CpZDS contained a 1713-bp ORF encoding a polypeptide of 570 amino acids. Phylogenetic analysis indicated that CpPSY shares homology with PSYs from Citrus, tomato, pepper, Arabidopsis, and the monocot PSY1 group, while CpPDS and CpZDS are most closely related to orthologs from Citrus and tomato. Expression analysis revealed fluctuations in CpPSY, CpPDS, and CpZDS transcript abundance and a non-coordinated regulation between the former and the two latter genes during fruit development in albedo and juice vesicles of white ('Duncan') and red ('Flame') grapefruits. A 3× higher upregulation of CpPSY expression in juice vesicles of red-fleshed 'Flame' as compared to white-fruited 'Duncan' was observed in the middle stages of fruit development, which correlates with the well documented accumulation pattern of lycopene in red grapefruit. Together with previous data, our results suggest that the primary mechanism controlling lycopene accumulation in red grapefruit involves the transcriptional upregulation of CpPSY, which controls the flux into the carotenoid pathway, and the downregulated expression of CpLCYB2, which controls the step of cyclization of lycopene in chromoplasts during fruit ripening. A correlation between CpPSY expression and fruit color evolution in red grapefruit is demonstrated.

Methylphenidate (MPH) is a drug that is licensed for treatment of ADHD and also narcolepsy. Monitoring of the parent drug and its major metabolite ritalinic acid (RA) in urine is considered necessary to ensure compliance with treatment programmes. A rapid, simple and sensitive liquid chromatography/tandem mass spectrometry (LC-MS/MS) assay was developed for the determination of MPH and its metabolite RA in human urine. After urine was diluted with water, methylphenidate, the major metabolite ritalinic acid, and d₆-amphetamine as the internal standard were resolved on a PFP propyl column using gradient elution of 0.02% ammonium formate and acetonitrile. The total analysis time was 13.5 min. The three compounds were detected using electrospray ionisation in the positive mode. Standard curves were linear over the concentration range 5-5000 μg/L (r>0.997), bias was ≤ ±20%, intra- and inter-day coefficients of variation (imprecision) were <8% and the limit of detection was 5 μg/L. The limit of quantitation was set at 100 μg/L. Matrix effects were up to 140% but these were accounted for by the internal standard. The assay is being used successfully in clinical practice to enhance the safe and effective use of methylphenidate., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Background: Citrus canker disease caused by the bacterial pathogen Xanthomonas citri subsp. citri (Xcc) has become endemic in areas where high temperature, rain, humidity, and windy conditions provide a favourable environment for the dissemination of the bacterium. Xcc is pathogenic on many commercial citrus varieties but appears to elicit an incompatible reaction on the citrus relative Fortunella margarita Swing (kumquat), in the form of a very distinct delayed necrotic response. We have developed subtractive libraries enriched in sequences expressed in kumquat leaves during both early and late stages of the disease. The isolated differentially expressed transcripts were subsequently sequenced. Our results demonstrate how the use of microarray expression profiling can help assign roles to previously uncharacterized genes and elucidate plant pathogenesis-response related mechanisms. This can be considered to be a case study in a citrus relative where high throughput technologies were utilized to understand defence mechanisms in Fortunella and citrus at the molecular level., Results: cDNAs from sequenced kumquat libraries (ESTs) made from subtracted RNA populations, healthy vs. infected, were used to make this microarray. Of 2054 selected genes on a customized array, 317 were differentially expressed (P < 0.05) in Xcc challenged kumquat plants compared to mock-inoculated ones. This study identified components of the incompatible interaction such as reactive oxygen species (ROS) and programmed cell death (PCD). Common defence mechanisms and a number of resistance genes were also identified. In addition, there were a considerable number of differentially regulated genes that had no homologues in the databases. This could be an indication of either a specialized set of genes employed by kumquat in response to canker disease or new defence mechanisms in citrus., Conclusion: Functional categorization of kumquat Xcc-responsive genes revealed an enhanced defence-related metabolism as well as a number of resistant response-specific genes in the kumquat transcriptome in response to Xcc inoculation. Gene expression profile(s) were analyzed to assemble a comprehensive and inclusive image of the molecular interaction in the kumquat/Xcc system. This was done in order to elucidate molecular mechanisms associated with the development of the hypersensitive response phenotype in kumquat leaves. These data will be used to perform comparisons among citrus species to evaluate means to enhance the host immune responses against bacterial diseases.