The mediating role of reflective functioning and general psychopathology in the relationship between childhood conduct disorder and adult aggression among offenders.

BACKGROUND: The nature of the pathway from conduct disorder (CD) in adolescence to antisocial behavior in adulthood has been debated and the role of certain mediators remains unclear. One perspective is that CD forms part of a general psychopathology dimension, playing a central role in the developmental trajectory. Impairment in reflective functioning (RF), i.e., the capacity to understand one's own and others' mental states, may relate to CD, psychopathology, and aggression. Here, we characterized the structure of psychopathology in adult male-offenders and its role, along with RF, in mediating the relationship between CD in their adolescence and current aggression. METHODS: A secondary analysis of pre-treatment data from 313 probation-supervised offenders was conducted, and measures of CD symptoms, general and specific psychopathology factors, RF, and aggression were evaluated through clinical interviews and questionnaires. RESULTS: Confirmatory factor analyses indicated that a bifactor model best fitted the sample's psychopathology structure, including a general psychopathology factor (p factor) and five specific factors: internalizing, disinhibition, detachment, antagonism, and psychoticism. The structure of RF was fitted to the data using a one-factor model. According to our mediation model, CD significantly predicted the p factor, which was positively linked to RF impairments, resulting in increased aggression. CONCLUSIONS: These findings highlight the critical role of a transdiagnostic approach provided by RF and general psychopathology in explaining the link between CD and aggression. Furthermore, they underscore the potential utility of treatments focusing on RF, such as mentalization-based treatment, in mitigating aggression in offenders with diverse psychopathologies.

The Impact of a Digital Contraceptive Decision Aid on User Outcomes: Results of an Experimental, Clinical Trial.

BACKGROUND: Nearly 40% of unplanned pregnancies in the USA are the result of inconsistent or incorrect contraceptive use. Finding ways to increase women's comfort and satisfaction with contraceptive use is therefore critical to public health. One promising pathway for improving patient outcomes is through the use of digital decision aids that assist women and their physicians in choosing a contraceptive option that women are comfortable with. Testing the ability of these aids to improve patient outcomes is therefore a necessary first step toward incorporating this technology into traditional physician appointments. PURPOSE: To evaluate the effectiveness of a novel contraceptive decision aid at minimizing decisional conflict and increasing comfort with contraception among adult women. METHODS: In total, 310 adult women were assigned to use either the Tuune contraceptive decision aid or a control aid modeled after a leading online contraceptive prescriber's patient intake form. Participants then completed self-report measures of decisional conflict, contraceptive expectations, satisfaction, and contraceptive use intentions. Individual between-subjects analysis of variance (ANOVA) models were used to examine these outcomes. RESULTS: Women using the Tuune decision aid (vs. those using the control aid) reported lower decisional conflict, more positive contraceptive expectations, greater satisfaction with the decision aid and recommendation, and more positive contraceptive use intentions. CONCLUSIONS: Use of Tuune improved each of the predicted patient outcomes relative to a control decision aid. Online decision aids, particularly when used alongside physician consultations, may be an effective tool for increasing comfort with contraceptive use. CLINICAL TRIALS REGISTRATION #: NCT05177783, ClinicalTrials.gov, https://clinicaltrials.gov/ct2/show/NCT05177783.

Digital decision aids that help women and their physicians choose contraceptive options that women are most comfortable with present one promising way to improve contraceptive use outcomes, such as avoiding unplanned pregnancies. However, current decision aids have been found to struggle in helping improve women's satisfaction with and confidence in their contraceptive choices. The aim of this study was to test the effectiveness of a new digital decision aid, named Tuune, at helping improve women's confidence and comfort with contraception. Three hundred and ten adult women were randomly assigned to use and then receive a contraceptive recommendation from either the Tuune decision aid or a control aid designed after leading traditional health intake forms. Women's confidence and satisfaction with the aids, as well as their contraceptive recommendation, were then compared between groups. We found good evidence to suggest that women using the Tuune contraceptive decision aid were more satisfied and positive about their contraceptive choices and reported greater intentions to use contraception with increased confidence compared to women who used the control decision aid. New online decision aids, like Tuune, may be an effective tool for increasing women's comfort and experiences using contraception.

A change in metal cation switches selectivity of a phospholipid sensor from phosphatidic acid to phosphatidylserine.

Phosphatidic acid and phosphatidylserine are anionic phospholipids with emerging signalling roles in cells. Determination of how phosphatidic acid and phosphatidylserine change location and quantity in cells over time requires selective fluorescent sensors that can distinguish these two anionic phospholipids. However, the design of such synthetic sensors that can selectively bind and respond to a single phospholipid within the complex membrane milieu remains challenging. In this work, we present a simple and robust strategy to control the selectivity of synthetic sensors for phosphatidic acid and phosphatidylserine. By changing the coordination metal of a dipicolylamine (DPA) ligand from Zn(II) to Ni(II) on the same synthetic sensor with a peptide backbone, we achieve a complete switch in selectivity from phosphatidic acid to phosphatidylserine in model lipid membranes. Furthermore, this strategy was largely unaffected by the choice and the position of the fluorophores. We envision that this strategy will provide a platform for the rational design of targeted synthetic phospholipid sensors to probe plasma and intracellular membranes.

Attachment style and children and young people with chronic dermatological conditions.

BACKGROUND: Dermatological conditions are common in childhood and, in their more severe forms, can cause pain, disability and social marginalisation. Despite attachment being a known factor contributing to psychological and physiological development in childhood and several adult studies showing associations between attachment and dermatology outcomes (Tomas-Aragones, 2018), attachment in young dermatology patients has not been investigated. OBJECTIVES: This study examined if (1) 8-16-year-olds with chronic dermatological conditions were more likely to show attachment insecurity than general population peers; (2) attachment style was linked to psychological functioning; and (3) facial involvement was associated with attachment insecurity. METHOD: One hundred and twenty-two 8-16-year-olds attending a specialist paediatric dermatological service were compared on the Child Attachment Interview (CAI) to general population data. The Strengths and Difficulties Questionnaire (SDQ) was used to measure psychosocial functioning. RESULTS: The dermatology group was significantly more likely to be insecurely attached than their general population peers (χ2 [1] = 4.76, p < .05). The secure group self-reported significantly better psychological functioning on all indices compared with the insecure group (Total Difficulties: F[1,89] = 15.30, p < .001). There were no significant differences between secure and insecure groups on parent-reported psychological measures (Total Difficulties: F[1,94] = 0.67, p = .42). Children with facial involvement were not significantly more likely to be insecurely attached. CONCLUSIONS: Increased risk of attachment insecurity, particularly in the anxious pre-occupied category, as well as an association between attachment and psychosocial functioning resonated with adult studies suggesting that further research about the role of attachment with young dermatology patients is warranted.

Transmembrane Transport of Inorganic Phosphate by a Strapped Calix[4]pyrrole.

Synthetic anion receptors are increasingly being explored for the transport of anions across lipid membranes because of their potential therapeutic applications. A considerable amount of research focuses on the transport of chloride, whereas the transmembrane transport of inorganic phosphate has not been reported to date, despite the biological relevance of this anion. Here we present a calix[4]pyrrole with a bisurea strap that functions as a receptor and transporter for H2PO4-, relying on the formation of eight hydrogen bonds and efficient encapsulation of the anion. Using a phosphate-sensitive lanthanide probe and 31P NMR spectroscopy, we demonstrate that this receptor can transport phosphate into vesicles by H2PO4-/Cl- antiport, H2PO4- uniport, and Cs+/H2PO4- symport mechanisms. This first example of inorganic phosphate transport by a neutral receptor opens perspectives for the future development of transporters for various biological phosphates.

Multidisciplinary Pain Management: A Tale of Two Outcomes.

Economic implications of pain management. By Loeser JD. Acta Anaesthesiol Scand 1999; 43:957-95. Reprinted with permission. Multidisciplinary pain management was an invention of John J. Bonica, M.D. He started the Multidisciplinary Pain Clinic at the University of Washington in 1960. This clinical service evolved over the years, and when John Loeser, M.D., became its director in 1982, he collaborated with Bill Fordyce, Ph.D., to create what was known as "the structured program." The program has served as the model for pain treatment programs throughout the world, many of which have fared better than that at the University of Washington. The migration of Stephen Butler, M.D., to Uppsala, Sweden, in 2000 has given us the opportunity to contrast multidisciplinary pain management in the Nordic countries with that in the United States.

A macrocyclic fluorescent probe for the detection of citrate.

We present a macrocyclic fluorescent probe for the detection of citrate. This receptor binds citrate through hydrogen-bonding interactions in aqueous solutions, and exhibits a turn-on in fluorescence in response to binding. The presence of common biologically relevant dicarboxylate species does not significantly impact the fluorescence response. We have demonstrated the utility of this probe with the staining of murine splenocytes, and identified different basal levels of citrate present in immune cell subsets via flow cytometry analysis.

Monofunctionalized Fluorinated Bambusurils and Their Conjugates for Anion Transport and Extraction.

Bambusurils are macrocyclic molecules that are known for their high binding affinity and selectivity toward anions. Here, we present the preparation of two bambusurils bearing fluorinated substituents and one carboxylic function. These monofunctionalized bambusurils were conjugated with crown ether and cholesterol units. The resulting conjugates were successfully tested in liquid-liquid extraction of inorganic salts and chloride/bicarbonate transport across lipid bilayers.

Anion binding to a cationic europium(III) probe enables the first real-time assay of heparan sulfotransferase activity.

Sulfotransferases constitute a ubiquitous class of enzymes which are poorly understood due to the lack of a convenient tool for screening their activity. These enzymes use the anion PAPS (adenosine-3'-phosphate-5'-phosphosulfate) as a donor for a broad range of acceptor substrates, including carbohydrates, producing sulfated compounds and PAP (adenosine-3',5'-diphosphate) as a side product. We present a europium(III)-based probe that binds reversibly to both PAPS and PAP, producing a larger luminescence enhancement with the latter anion. We exploit this greater emission enhancement with PAP to demonstrate the first direct real-time assay of a heparan sulfate sulfotransferase using a multi-well plate format. The selective response of our probe towards PAP over structurally similar nucleoside phosphate anions, and over other anions, is investigated and discussed. This work opens the possibility of investigating more fully the roles played by this enzyme class in health and disease, including operationally simple inhibitor screening.

Dissecting transmembrane bicarbonate transport by 1,8-di(thio)amidocarbazoles.

Synthetic ionophores able to transport bicarbonate and chloride anions across lipid bilayers are appealing for their wide range of potential biological applications. We have studied the bicarbonate and chloride transport by carbazoles with two amido/thioamido groups using a bicarbonate-sensitive europium(III) probe in liposomes and found a highly remarkable transporter concentration dependence. This can be explained by a combination of two distinct transport mechanisms: HCO3-/Cl- exchange and a combination of unassisted CO2 diffusion and HCl transport, of which the respective contributions were quantified. The compounds studied were found to be highly potent HCl transporters. Based on the mechanistic insights on anion transport, we have tested the antimicrobial activity of these compounds and found a good correlation with their ion transport properties and a high activity against Gram-positive bacteria.

Antisocial cognition as a mediator of the peer influence effect and peer selection effect in antisocial adolescents.

The peer influence and peer selection effects are two widely replicated findings in the criminological literature that refer to the predictive relationship between antisocial behaviour and delinquent peer association as well as between delinquent peer association and antisocial behaviour, respectively. Research suggests that antisocial cognition might constitute a causal mechanism underlying part of these effects. This study investigated the extent that the peer influence and peer selection effects are mediated by one key aspect of antisocial cognition-beliefs and attitudes supporting peer conflict. This study examined whether beliefs and attitudes supporting peer conflict mediated the relationship between delinquent peer association and volume of self-reported antisocial behaviour and vice-versa, across a 1-year follow-up period, in 683 (433 male, 250 female) British adolescents (mean age: 13.8 years) with a history of serious antisocial behaviour. Participants completed measures at baseline and 6, 12 and 18 months thereafter. Findings indicated that beliefs and attitudes supporting peer conflict partially mediated the peer influence and peer selection effects, explaining a substantial proportion of the total effect in the peer influence (i.e., 26%) and peer selection (i.e., 17%) models. These results suggest that beliefs and attitudes supporting peer conflict could explain part of the mechanism underlying the peer influence and peer selection effects in adolescents with a history of serious antisocial behaviour.

Transmembrane Transport of Bicarbonate Unravelled.

Invited for the cover of this issue are Dr. Stephen Butler, Dr. Hennie Valkenier and co-workers at Université Libre de Bruxelles, Loughborough University, Masaryk University, and the University of Bristol. The image depicts the transport of bicarbonate anions versus the spontaneous diffusion of CO2 across the lipid bilayer of a liposome. Read the full text of the article at 10.1002/chem.202100491.

Transmembrane Transport of Bicarbonate Unravelled*.

Anion receptors can be used to transport ions across lipid bilayers, which has potential for therapeutic applications. Synthetic bicarbonate transporters are of particular interest, as defects in transmembrane transport of bicarbonate are associated with various diseases. However, no convenient method exists to directly observe bicarbonate transport and study the mechanisms involved. Here, an assay is presented that allows the kinetics of bicarbonate transport into liposomes to be monitored directly and with great sensitivity. The assay utilises an encapsulated europium(III) complex, which exhibits a large increase in emission intensity upon binding bicarbonate. Mechanisms involving CO2 diffusion and the dissipation of a pH gradient are shown to be able to lead to an increase in bicarbonate concentration within liposomes, without transport of the anion occurring at all. By distinguishing these alternative mechanisms from actual bicarbonate transport, this assay will inform the future development of bicarbonate transporters.

A Chiral Lanthanide Tag for Stable and Rigid Attachment to Single Cysteine Residues in Proteins for NMR, EPR and Time-Resolved Luminescence Studies.

A lanthanide-binding tag site-specifically attached to a protein presents a tool to probe the protein by multiple spectroscopic techniques, including nuclear magnetic resonance, electron paramagnetic resonance and time-resolved luminescence spectroscopy. Here a new stable chiral LnIII tag, referred to as C12, is presented for spontaneous and quantitative reaction with a cysteine residue to generate a stable thioether bond. The synthetic protocol of the tag is relatively straightforward, and the tag is stable for storage and shipping. It displays greatly enhanced reactivity towards selenocysteine, opening a route towards selective tagging of selenocysteine in proteins containing cysteine residues. Loaded with TbIII or TmIII ions, the C12 tag readily generates pseudocontact shifts (PCS) in protein NMR spectra. It produces a relatively rigid tether between lanthanide and protein, which is beneficial for interpretation of the PCSs by single magnetic susceptibility anisotropy tensors, and it is suitable for measuring distance distributions in double electron-electron resonance experiments. Upon reaction with cysteine or other thiol compounds, the TbIII complex exhibits a 100-fold enhancement in luminescence quantum yield, affording a highly sensitive turn-on luminescence probe for time-resolved FRET assays and enzyme reaction monitoring.

Recommendations for validation testing of home pregnancy tests (HPTs) in Europe.

Home pregnancy tests (HPTs) available in Europe include accuracy and other performance claims listed on their packaging. Due to the lack of guidance on the standardisation of such products, it is often difficult to replicate these claims when tested on a clinical sample, whether in a laboratory setting or by lay users. The In Vitro Diagnostic Regulation is a set of requirements that mandate comprehensive validation data on human pregnancy tests and other in vitro devices. It is due to replace the current European Directive (98/79/EC) and fully implemented in Europe by 2022. In June 2019, a panel of seven experts convened to discuss the validation studies required to provide the information needed to meet the new regulation for HPTs in Europe and proposed 15 recommendations for best practice. Defining best practice at all stages of validation of these important tests may ensure that tests marketed in Europe are fit for purpose, enabling lay users to be confident of the high quality of the HPT results they obtain. The panelists believe that the recommendations proposed here for the validation of HPTs may constructively contribute to improved standardisation of validation procedures in Europe.

Invited review: Use of assisted reproduction techniques to accelerate genetic gain and increase value of beef production in dairy herds.

The contribution of the calf enterprise to the profit of the dairy farm is generally considered small, with beef bull selection on dairy farms often not considered a high priority. However, this is likely to change in the future as the rapid rate of expansion of the dairy herd in some countries is set to plateau and improvements in dairy herd fertility combine to reduce the proportion of dairy breed calves required on dairy farms. This presents the opportunity to increase the proportion of beef breed calves born, increasing both the value of calf sales and the marketability of the calves. Beef embryos could become a new breeding tool for dairies as producers need to reassess their breeding policy as a consequence of welfare concerns and poor calf prices. Assisted reproductive technologies can contribute to accelerated genetic gain by allowing an increased number of offspring to be produced from genetically elite dams. There are the following 3 general classes of donor females of interest to an integrated dairy-beef system: (1) elite dairy dams, from which oocytes are recovered from live females using ovum pick-up and fertilized in vitro with semen from elite dairy bulls; (2) elite beef dams, where the oocytes are recovered from live females using ovum pick-up and fertilized with semen from elite beef bulls; and (3) commercial beef dams (≥50% beef genetics), where ovaries are collected from the abattoir postslaughter, and oocytes are fertilized with semen from elite beef bulls that are suitable for use on dairy cows (resulting embryo with ≥75% beef genetics). The expected benefits of these collective developments include accelerated genetic gain for milk and beef production in addition to transformation of the dairy herd calf crop to a combination of good genetic merit dairy female calves and premium-quality beef calves. The aim of this review is to describe how these technologies can be harnessed to intensively select for genetic improvement in both dairy breed and beef breed bulls suitable for use in the dairy herd.

Identification of the blue light intensity administered to one eye required to suppress bovine plasma melatonin and investigation into effects on milk production in grazing dairy cows.

Long-day photoperiod is known to positively affect milk production in confinement dairy systems, and it has been hypothesized that pineal melatonin (MT) secretion plays a substantial role in this process. Specialized mammalian photoreceptors that regulate MT secretion are optimally stimulated by short wavelength blue light. We investigated the blue light intensity administered to one eye required to suppress MT secretion in nonlactating dairy cows, and subsequently examined effects on milk production in grazing dairy cows. Following a 14-d light-dark 8:16 h environmental conditioning period, 5 nonlactating Holstein-Friesian cows were exposed to treatments of <1, 70, 125, 175, and 225 lx for 8 additional hours using a 5 × 5 Latin square design. Light was administered via headpieces fitted with light-emitting diodes emitting blue light (465 nm) to the right eye. All cows were then exposed to a light-dark 16:8 h cycle for one night via the indoor lighting system (>200 lx white light). Plasma samples collected at regular intervals were assayed for MT. A dose-dependent effect of light treatment on mean circulating MT concentrations (and 95% CI) was observed [9.4 (7.2, 12.3), 5.0 (3.8, 6.6), 4.4 (3.3, 5.7), 3.3 (2.5, 4.3) and 1.7 (1.3, 2.3) pg/mL for treatments of 0, 70, 125, 175, and 225 lx, respectively. Only the 225 lx treatment acutely suppressed plasma melatonin concentration to levels similar to the light-dark 16:8 h treatment [1.9 (1.4, 2.5) pg/mL]. Forty spring-calving cows were blocked on parity, calving date and Economic Breeding Index for milk production and assigned to the control treatment or blue light to a single eye (LT) treatment from calving through 32 wk of lactation. The cows assigned to LT treatment were fitted with headpieces providing 225 lx of blue light to the right eye from 1700 until 0000 h. Mean milk production (and 95% CI) during 32 wk of lactation was not affected by treatment [20.3 (19.3, 21.3) vs. 20.9 (19.8, 22.0) kg/d, control and LT, respectively]. Within multiparous cows, a treatment by week interaction was detected, whereby LT treatment increased milk production during the first 12 wk of lactation [25.8 (24.3, 27.3) vs. 28.0 (26.5, 29.5) kg/d; +8.5%], but had no effect thereafter. Treatment did not affect plasma insulin-like growth factor 1. We identified the blue light intensity to one eye required to acutely suppress MT concentrations. Transient favorable effects on milk production were observed in multiparous cows. It remains unclear how single-eye blue light treatment affects galactopoiesis in grazing dairy cows, and further research is needed to explore whether this modality of light delivery represents a useful means to aid productivity in pasture-based dairy systems.

Molecular recognition and sensing of dicarboxylates and dicarboxylic acids.

The recognition and detection of dicarboxylic acids and dicarboxylates is of significance for a wide variety of applications, including medical diagnosis, monitoring of health and of environmental contaminants, and in industry. Hence small molecule receptors and sensors for dicarboxylic acids and dicarboxylates have great potential for applications in these fields. This review outlines the challenges faced in the recognition and detection of these species, strategies that have been used to obtain effective and observable interactions with dicarboxylic acids and dicarboxylates, and progress made in this field in the period from 2014 to 2020.

Evaluation of Abuse and Route of Administration of Extended-Release Tapentadol Among Treatment-Seeking Individuals, as Captured by the Addiction Severity Index-Multimedia Version (ASI-MV).

BACKGROUND: Tapentadol is a molecule incorporating mu opioid receptor agonism and norepinephrine reuptake inhibition to provide analgesia, with the potential for a lower incidence of gastrointestinal side effects than full mu opioid agonists. Postmarketing surveillance of tapentadol as an active pharmaceutical ingredient has consistently revealed low levels of abuse and diversion. OBJECTIVE: The purpose of the present study was to further characterize the abuse liability of tapentadol extended-release (ER) by evaluating the prevalence of past 30-day tapentadol ER abuse and reported routes of administration as compared with ER opioids with Food and Drug Administration (FDA) abuse-deterrent labeling ("ADF opioids") and ER opioids without FDA abuse-deterrent labeling ("non-ADF opioids"). METHODS: Data were collected from January 2014 through December 2017 from 776 centers located in 43 states throughout the United States using the Addiction Severity Index-Multimedia Version (ASI-MV), an instrument that is integral to the National Addictions Vigilance Intervention and Prevention Program (NAVIPPRO, Inflexxion, an IBH Company, Costa Mesa, CA, USA). RESULTS: Tapentadol ER had lower rates of past 30-day abuse than ADF ER and non-ADF ER opioid comparators, both at a population level and when adjusted for drug utilization. Tapentadol ER was primarily abused orally, although it was also abused through alternate routes of administration. Cumulative rates of tapentadol ER abuse by alternative routes of administration were lower than both ADF and non-ADF ER opioid comparators, although large confidence intervals resulting from the small sample size of reported tapentadol ER use limit firm conclusions. CONCLUSIONS: In summary, tapentadol ER was found to have lower rates of both past 30-day abuse and use via alternate routes of administration, specifically snorting and smoking, than ADF and non-ADF ER comparators.

Bioinformatic identification of euploid and aneuploid embryo secretome signatures in IVF culture media based on MALDI-ToF mass spectrometry.

PURPOSE: Embryo genotyping in IVF clinics aims to identify aneuploid embryos, and current methodologies rely on costly, invasive and time-consuming approaches such as PGT-A screening. MALDI-ToF-based mass spectral analysis of embryo culture has been demonstrated to be a non-invasive, affordable and accurate technique that is able to capture secretome profiles from embryo culture media extremely quick. Thus, aneuploid embryo genotypes can be distinguished from euploids from these profiles towards the development of novel embryo selection tools. METHODS: A retrospective cohort study, including 292 spent media samples from embryo cultures collected from a single IVF clinic in USA. There were 149 euploid and 165 aneuploid embryos previously analysed by PGT-A next-generation sequencing techniques. Secretome mass spectra of embryos were generated using MALDI-ToF mass spectrometry in the UK. Data was systematically analysed using a fully automated and ultra-fast bioinformatic pipeline developed for the identification of mass spectral signatures. RESULTS: Distinct spectral patterns were found for euploid and aneuploid genotypes in embryo culture media. We identified 12 characteristic peak signatures for euploid and 17 for aneuploid embryos. Data analysis also revealed a high degree of complementarity among regions showing that 22 regions are required to differentiate between genotypes with a sensitivity of 84% and a false positive rate of 18%. CONCLUSION: Ultra-fast and fully automated screening of an embryo genotype is possible based on multiple combinations of specific mass spectral peak signatures. This constitutes a breakthrough towards the implementation of non-invasive and ultra-fast tools for embryo selection immediately prior to transfer.