Hierarchically embedded scales of movement shape the social networks of vampire bats.

Social structure can emerge from hierarchically embedded scales of movement, where movement at one scale is constrained within a larger scale (e.g. among branches, trees, forests). In most studies of animal social networks, some scales of movement are not observed, and the relative importance of the observed scales of movement is unclear. Here, we asked: how does individual variation in movement, at multiple nested spatial scales, influence each individual's social connectedness? Using existing data from common vampire bats (Desmodus rotundus), we created an agent-based model of how three nested scales of movement-among roosts, clusters and grooming partners-each influence a bat's grooming network centrality. In each of 10 simulations, virtual bats lacking social and spatial preferences moved at each scale at empirically derived rates that were either fixed or individually variable and either independent or correlated across scales. We found that numbers of partners groomed per bat were driven more by within-roost movements than by roost switching, highlighting that co-roosting networks do not fully capture bat social structure. Simulations revealed how individual variation in movement at nested spatial scales can cause false discovery and misidentification of preferred social relationships. Our model provides several insights into how nonsocial factors shape social networks.

Variation in oxidative status, but not structural and physiological development, associated with changing ontogenetic environments.

Despite the potential for temporally dependent relationships between trait values and fitness (e.g. as juveniles approach life-stage transitions such as fledging), how developmental stage affects canalization (a measure of robustness to environmental variation) of morphological and physiological traits is rarely considered. To test the sensitivity of morphological and physiological traits to environmental variation in two developmental stages, we manipulated brood size at hatch in European starlings (Sturnus vulgaris) and cross-fostered chicks between enlarged and reduced broods approaching fledging. We measured body size (mass, tarsus, wing length) and physiological state (aerobic capacity, oxidative status) at asymptotic mass on day 15, then cross-fostered chicks between 'high' and 'low' quality environments and assessed the same traits again on day 20, after 5 days of pre-fledging mass recession. Chicks in reduced broods were heavier at asymptotic mass and had lower reactive oxygen metabolites than enlarged broods, whereas structural size, aerobic capacity and antioxidant capacity were unaffected by experimental brood size. The observed canalization of structural and physiological traits during early development was maintained after cross-fostering, during late development. However, in contrast to early development, antioxidant capacity approaching fledging appeared sensitive to environmental conditions, as trajectories varied by cross-fostering treatment. Elevated reactive oxygen metabolites observed after early development in enlarged brood chicks were maintained after cross-fostering, suggesting that canalized development in low-quality environments could produce oxidative costs that carry over between life stages, even when conditions improve. These data reveal trait-specific relationships between environmental conditions and development, and highlight how natal environment effects may vary by developmental stage.

Implementing ABPM into Clinical Practice.

PURPOSE OF REVIEW: To review the data supporting the use of ambulatory blood pressure monitoring (ABPM), and to provide practical guidance for practitioners who are establishing an ambulatory monitoring service. RECENT FINDINGS: ABPM results more accurately reflect the risk of cardiovascular events than do office measurements of blood pressure. Moreover, many patients with high blood pressure in the office have normal blood pressure on ABPM-a pattern known as white coat hypertension-and have a prognosis similar to individuals who are normotensive in both settings. For these reasons, ABPM is recommended by the US Preventive Services Task Force to confirm the diagnosis of hypertension in patients with high office blood pressure before medical therapy is initiated. Similarly, the 2017 ACC/AHA High Blood Pressure Clinical Practice Guideline advocates the use of out-of-office blood pressure measurements to confirm hypertension and evaluate the efficacy of blood pressure-lowering medications. In addition to white coat hypertension, blood pressure phenotypes that are associated with increased cardiovascular risk and that can be recognized by ABPM include masked hypertension-characterized by normal office blood pressure but high values on ABPM-and high nocturnal blood pressure. In this review, best practices for starting a clinical ABPM service, performing an ABPM monitoring session, and interpreting and reporting ABPM data are described. ABPM is a valuable adjunct to careful office blood pressure measurement in diagnosing hypertension and in guiding antihypertensive therapy. Following recommended best practices can facilitate implementation of ABPM into clinical practice.

[Electromyographic Analysis of Neck Muscles at a Simulated Rear-end Impact in Healthy Subjects]. / Elektromyografische Analyse der Halsmuskulatur bei simulierter Heckkollision an gesunden Probanden.

BACKGROUND: Despite the introduction of safety belts and head restraints, severe neck injuries still occur in traffic accidents. Whether there are anthropometric factors or muscular properties, that affect the reflex times during a rear-end collision, and if they have predictive value for the expected trauma, should be reviewed in this investigation. METHODS: In 32 male volunteers anthropometric data and the maximal strength of their cervical musculature were measured. Thereafter, the volunteers were subjected to a simulated rear-end collision with a speed of 2 km/h. The impending crash was not announced to the subjects during the first test run. The situation was repeated several times to test the effect of warning. During the investigation, the muscle activity of neck and shoulder muscles was derived with surface electromyography (EMG). RESULTS: There was a strong correlation between the reflex time of the anterior neck muscles and the strength of that muscle group (r=-0.75; r²=0.57). In addition, the neck length correlated to the reflex time (r=-0.67; r²=0.45). The warning provided for the volunteers influences the EMG as well. The reflex times of the subjects were shorter (p Alle statistischen Berechnungen wurden mit IBM SPSS Statistics (Version 18; IBM Inc., Armonk, USA), sowie dem Programm Excel, (Microsoft, Redmond, USA) vorgenommen. Die Reflexzeiten wurden den anthropometrischen Daten, sowie der Muskelkraft gegenübergestellt und nach Pearson korreliert. Als eine angemessene Korrelation wurde das Quadrat des Korrelationskoeffizienten bei Werten r²>0,4 festgelegt. Außerdem wurden die Mediane der Reflexzeiten, der verschiedenen Kollisionssituationen miteinander verglichen. Das Signifikanz-Niveau wurde auf p<0,05 festgelegt. 0.05), when they knew about the impending collision. CONCLUSION: A high force capacity of anterior neck muscles has preventive value to reduce the consequences of whiplash accidents. The use and development of early warning systems in cars should be supported.

Reduced plasma glycine concentration in healthy and chronically diseased older adults: a marker of visceral adiposity?

BACKGROUND: Previous studies have shown that a reduced plasma concentration of the amino acid glycine (Gly) is associated with intra-abdominal obesity, but the mechanism remains unclear. OBJECTIVES: This study aimed to investigate whether lower plasma Gly concentrations in older adults are independently associated with (visceral) adiposity, age, sex, presence of chronic disease, and glucose intolerance, and whether they are caused by a reduced Gly whole-body production (WBP) and/or increased Gly disposal capacity. METHODS: We studied 102 older adults (47 males/55 females, 68.5 ± standard deviation 6.4 y) without comorbidities and 125 older adults with chronic obstructive pulmonary disease (COPD) (58 males/67 females, 69.7 ± 8.6 y). We assessed body composition and visceral adipose tissue (VAT) by dual-energy x-ray absorptiometry and muscle function by dynamometry. We measured postabsorptive plasma amino acid profile and glucose, followed by pulse administration of stable isotope-labeled Gly ([2,2-2H2]), and blood sampling was performed to measure the WBP of Gly. Results are expressed as means and 95% confidence intervals (CIs). RESULTS: We found a lower plasma Gly concentration in healthy males and males with COPD than in females (Healthy: 211; 95% CI: 193,230 compared with 248; 95% CI: 225,271; COPD: 200; 95% CI: 186,215 compared with 262: 95% CI: 241, 283; P < 0.0001, respectively), with no difference between healthy and COPD groups. A negative relationship was found between unadjusted plasma Gly and VAT mass (R2: 0.16; slope: -1.7; 95% CI: -2.4, -1.2; P < 0.0021), but not with total body fat or fasting glucose. The strong association between lower plasma Gly and increased VAT mass in older adults was independent of age, sex, body weight, lean mass or body mass index, and the presence of COPD. Inclusion of these covariates increased the R2 to 0.783. We found no relation between the VAT and WBP of Gly (P = 0.35) or Gly clearance (P = 0.187) when lean mass was considered. CONCLUSIONS: Reduced plasma Gly in older adults can be considered a marker of visceral adiposity, independent of sex, age, body composition, presence of chronic disease, and whole-body Gly production or clearance. This study was registered on clinicaltrials.gov as NCT01787682, NCT02082418, NCT02157844, NCT02770092, NCT02780219, NCT03796455, and NCT04461236.

Estimating Breakfast Characteristics Using Continuous Glucose Monitoring and Machine Learning in Adults With or at Risk of Type 2 Diabetes.

BACKGROUND: Continuous glucose monitoring (CGM) systems allow detailed assessment of postprandial glucose responses (PPGR), offering new insights into food choices' impact on dysglycemia. However, current approaches to analyze PPGR using a CGM require manual meal logging, limiting the scalability of CGM-driven applications like personalized nutrition and at-home diabetes risk assessment. OBJECTIVE: We propose a machine learning (ML) framework to automatically identify and characterize breakfast-related PPGRs from CGM profiles in adults at risk of or living with noninsulin-treated type 2 diabetes (T2D). METHODS: Our PPGR estimation framework uses a random forest ML algorithm trained on 15 adults without diabetes who wore a CGM for up to four weeks. The algorithm performance was evaluated on a held-out subset of the participants' CGM data as well as on an external validation data set of 36 individuals at risk for or with noninsulin-treated T2D. RESULTS: Our algorithm's estimations of breakfast PPGRs displayed no statistically significant differences to annotated PPGRs, in terms of incremental area under the curve and glucose rise (P > .05 for both data sets), while a small difference in prebreakfast glucose was found in the nondiabetes data set (P = .005) but not in the validation T2D data set (P = .18). CONCLUSIONS: We designed an ML framework to automatically estimate the timing of meal events from CGM data in individuals without diabetes and in individuals at risk or with T2D. This could provide a more scalable approach for analyzing postprandial glycemia, increasing the feasibility of CGM-based precision nutrition and diabetes risk assessment applications.

Parental developmental experience affects vocal learning in offspring.

Cultural and genetic inheritance combine to enable rapid changes in trait expression, but their relative importance in determining trait expression across generations is not clear. Birdsong is a socially learned cognitive trait that is subject to both cultural and genetic inheritance, as well as being affected by early developmental conditions. We sought to test whether early-life conditions in one generation can affect song acquisition in the next generation. We exposed one generation (F1) of nestlings to elevated corticosterone (CORT) levels, allowed them to breed freely as adults, and quantified their son's (F2) ability to copy the song of their social father. We also quantified the neurogenetic response to song playback through immediate early gene (IEG) expression in the auditory forebrain. F2 males with only one corticosterone-treated parent copied their social father's song less accurately than males with two control parents. Expression of ARC in caudomedial nidopallium (NCM) correlated with father-son song similarity, and patterns of expression levels of several IEGs in caudomedial mesopallium (CMM) in response to father song playback differed between control F2 sons and those with a CORT-treated father only. This is the first study to demonstrate that developmental conditions can affect social learning and neurogenetic responses in a subsequent generation.

Females have a different metabolic response to critical illness, measured by comprehensive amino acid flux analysis.

BACKGROUND: The trajectory from healthy to critical illness is influenced by numerous factors, including metabolism, which differs substantially between males and females. Whole body protein breakdown is substantially increased in critically ill patients, but it remains unclear whether there are sex differences that could explain the different health outcomes. Hence, we performed a secondary analysis of a study, where we used a novel pulse isotope method in critically ill and matched healthy males and females. METHODS: In 51 critically ill ICU patients (26 males, 15 females) and 49 healthy controls (36 males and 27 females), we assessed their general and disease characteristics and collected arterial(ized) blood in the postabsorptive state after pulse administration of 8 ml of a solution containing 18 stable AA tracers. In contrast to the original study, we now fitted the decay curves and calculated non-compartmental whole body amino acid production (WBP) and compartmental measurements of metabolism, including intracellular amino acid production. We measured amino acid enrichments and concentrations by LC-MS/MS and derived statistics using AN(C)OVA. RESULTS: Critically ill males and females showed an increase in the WBP of many amino acids, including those related to protein breakdown, but females showed greater elevations, or in the event of a reduction, attenuated reductions. Protein breakdown-independent WBP differences remained between males and females, notably increased glutamine and glutamate WBP. Only severely ill females showed a lower increase in WBP of many amino acids in comparison to moderately ill females, suggesting a suppressed metabolism. Compartmental analysis supported the observations. CONCLUSIONS: The present study shows that females have a different response to critical illness in the production of several amino acids and changes in protein breakdown, observations made possible using our innovative stable tracer pulse approach. CLINICAL TRIAL REGISTRY: Data are from the baseline measurements of study NCT02770092 (URL: https://clinicaltrials.gov/ct2/show/NCT02770092) and NCT03628365 (URL: https://clinicaltrials.gov/ct2/show/NCT03628365).

Obesity- and sex-related metabolism of arginine and nitric oxide in adults.

BACKGROUND: There is growing interest in the supplementation of arginine (Arg) and citrulline (Cit) in obesity due to their potential anti-obesogenic and anti-inflammatory properties. However, there is no consensus on the metabolic changes in Arg kinetics in obesity. OBJECTIVES: This exploratory cross-sectional study aimed to investigate the association between obesity, sex, and sex-by-obesity interaction on whole-body Arg kinetics in a large group of human subjects. METHODS: We studied 83 nonobese [BMI (kg/m2) <30] and 80 morbidly obese (BMI >30) middle-aged individuals (40% males) enrolled in the MEDIT (Metabolism of Disease with Isotope Tracers) trial. After body-composition measurement by DXA, we collected arterial(ized) blood samples for amino acid (AA) concentrations, markers of inflammation [high-sensitivity C-reactive protein (hs-CRP)], liver function, and glucose in a postabsorptive state. We administered a pulse of AA stable tracers and measured whole-body production (WBP) of Arg, Cit, ornithine (Orn), phenylalanine, and tyrosine, and calculated their clearance (disposal capacity) and metabolite interconversions [markers for NO and de novo Arg production, systemic Arg hydrolysis, and whole-body protein breakdown (wbPB)]. We measured plasma enrichments by LC-MS/MS and statistics by Fisher's exact test or analysis of (co)variance. Significance was set at P < 0.05. RESULTS: Obese individuals were normoglycemic and characterized by low-grade inflammation (P < 0.0001) and greater wbPB (P = 0.0298). We found lower plasma Cit concentration (P < 0.0001) in the obese group but no differences in the WBP of Arg, Cit, and Orn. Furthermore, we observed overproduction of NO (P < 0.0001) in obesity but lower de novo Arg production (P = 0.0007). The WBP of Arg was lower in females for almost all Arg-related AAs, except for plasma Cit and NO production. CONCLUSIONS: Alterations in Arg metabolism are present in morbid obesity. Further studies are needed to investigate if these changes could be related to factors such as increased Arg requirement in obesity or metabolic adaptation.

A Subset of Nucleus Accumbens Neurons Receiving Dense and Functional Prelimbic Cortical Input Are Required for Cocaine Seeking.

Background: Prelimbic cortical projections to the nucleus accumbens core are critical for cue-induced cocaine seeking, but the identity of the accumbens neuron(s) targeted by this projection, and the transient neuroadaptations contributing to relapse within these cells, remain unknown. Methods: Male Sprague-Dawley rats underwent cocaine or sucrose self-administration, extinction, and cue-induced reinstatement. Pathway-specific chemogenetics, patch-clamp electrophysiology, in vivo electrochemistry, and high-resolution confocal microscopy were used to identify and characterize a small population of nucleus accumbens core neurons that receive dense prelimbic cortical input to determine their role in regulating cue-induced cocaine and natural reward seeking. Results: Chemogenetic inhibition of prelimbic cortical projections to the nucleus accumbens core suppressed cue-induced cocaine relapse and normalized real-time cue-evoked increases in accumbens glutamate release to that of sucrose seeking animals. Furthermore, chemogenetic inhibition of the population of nucleus accumbens core neurons receiving the densest prelimbic cortical input suppressed cocaine, but not sucrose seeking. These neurons also underwent morphological plasticity during the peak of cocaine seeking in the form of dendritic spine expansion and increased ensheathment by astroglial processes at large spines. Conclusion: We identified and characterized a unique subpopulation of nucleus accumbens neurons that receive dense prelimbic cortical input. The functional specificity of this subpopulation is underscored by their ability to mediate cue-induced cocaine relapse, but not sucrose seeking. This subset of cells represents a novel target for addiction therapeutics revealed by anterograde targeting to interrogate functional circuits imbedded within a known network.

A cryogenic clamping technique that facilitates ultimate tensile strength determinations in tendons and ligaments.

OBJECTIVE: To describe the use of a cryogenic clamp of novel design for tensile strength testing of tendinous and ligamentous tissues with inherently high tensile strength. METHODS: Inexpensive, easily machined steel clamps were manufactured to facilitate rapid insertion into a standard wedge-screw grip apparatus installed on a testing system with a control system attached. The deep digital flexor tendon (DDFT) of six horses was trimmed to a uniform dumbbell shape and secured in clamps using partial submersion in liquid nitrogen for approximately 45 seconds and immediately tested. Approximate time between removal from liquid nitrogen and failure of tendon was four minutes. RESULTS: Failure was achieved in all tendons tested in a region approximating a midpoint between the clamps. Ultimate failure loads of up to 6745 N were achieved without slippage of the tissue from the grips. The ultimate tensile strength of the normal equine DDFT determined in this study was 111.82 ± 11.53 N/mm2, and the stress versus grip-to-grip elongation plots for our equine DDFT were representative of a standard non-linear elastic curve obtained in similar studies. CLINICAL SIGNIFICANCE: We present a low cost device for quantifying physical properties of specimens with high connective tissue concentrations and inherent high tensile strength. Results of this study indicate that this device provides a practical alternative to other more costly methods of adequately securing larger tendons and ligaments for tensile strength testing.

Role of age and neuroinflammation in the mechanism of cognitive deficits in sickle cell disease.

IMPACT STATEMENT: This study provides crucial information that could be helpful in the development of new or repurposing of existing therapies for the treatment of cognitive deficit in individuals with sickle cell disease (SCD). Its impact is in demonstrating for the first time that neuroinflammation and along with abnormal neuroplasticity are among the underlying mechanism of cognitive and behavioral deficits in SCD and that drugs such as minocycline which targets these pathophysiological mechanisms could be repurposed for the treatment of this life altering complication of SCD.

Elucidating cancer-vascular paracrine signaling using a human organotypic breast cancer cell extravasation model.

In cancer metastasis, extravasation refers to the process where tumor cells exit the bloodstream by crossing the endothelium and invade the surrounding tissue. Tumor cells engage in complex crosstalk with other active players such as the endothelium leading to changes in functional behavior that exert pro-extravasation effects. Most in vitro studies to date have only focused on the independent effects of molecular targets on the functional changes of cancer cell extravasation behavior. However, singular targets cannot combat complex interactions involved in tumor cell extravasation that affects multiple cell types and signaling pathways. In this study, we employ an organotypic microfluidic model of human vasculature to investigate the independent and combined role of multiple upregulated secreted factors resulting from cancer-vascular interactions during cancer cell extravasation. The device consists of a tubular endothelial vessel generated from induced pluripotent stem cell derived endothelial cells within a collagen-fibrinogen matrix with breast cancer cells injected through and cultured along the lumen of the vessel. Our system identified cancer-vascular crosstalk, involving invasive breast cancer cells, that results in increased levels of secreted IL-6, IL-8, and MMP-3. Our model also showed that upregulation of these secreted factors correlates with invasive/metastatic potential of breast cancer cells. We also used therapeutic inhibitors to assess the independent and combined role of multiple signaling factors on the overall changes in functional behavior of both the cancer cells and the endothelium that promote extravasation. Taken together, these results demonstrate the potential of our organotypic model in elucidating mechanisms through which cancer-vascular interactions can promote extravasation, and in conducting functional assessment of therapeutic drugs that prevent extravasation in cancer metastasis.

Maternal influences on binge eating behaviors in children.

Binge eating in childhood has been linked to adverse future health outcomes. Parental factors, such as parents' emotion regulation and executive functioning, are likely to influence children's self-regulatory behaviors, including eating. Executive functioning describes a range of higher-order cognitive functions such as planning, abstraction, inhibitory control and working memory, which involves the ability to learn, update and manipulate new information while managing distractions. No studies have examined associations between maternal emotion regulation and executive functioning and the child's maladaptive eating patterns, which was the goal of the present study. Forty-eight mother and child pairs completed self-report clinical measures of emotion dysregulation and attentional control, and mothers completed a brief neuropsychological battery, which included executive functioning measures. Child's disordered eating was measured with the Child Binge Eating Disorder Scale. Linear regression results indicated that mother's performance on a working memory task and child's emotion dysregulation was significantly associated with child's binge eating symptoms (R 2 = 0.34). These data, which reveal that maternal executive functioning is associated with self-regulatory behaviors in children, indicate a possible mechanism through which maladaptive eating behaviors may emerge early in development. This relationship merits further exploration in larger-scale prospective intergenerational studies.

Comprehensive metabolic amino acid flux analysis in critically ill patients.

Amino acid (AA) metabolism is severely disturbed in critically ill ICU patients. To be able to make a more scientifically based decision on the type of protein or AA nutrition to deliver in ICU patients, comprehensive AA phenotyping with measurements of plasma concentrations and whole body production (WBP) is needed. Therefore, we studied ICU patients and matched control subjects using a novel pulse isotope method to obtain in-depth metabolic analysis. In 51 critically ill ICU patients (SOFA~6.6) and 49 healthy controls, we measured REE and body composition/phase-angle using BIA. In the postabsorptive state, we collected arterial (ized) blood for CRP and AA. Then, we administered an 8 mL solution containing 18 stable AA tracers as a pulse and calculated WBP. Enrichments: LC-MS/MS and statistics: t-test, ANCOVA. Compared to healthy, critically ill ICU patients had lower phase-angle (p < 0.00001), and higher CRP (p < 0.0001). Most AA concentrations were lower in ICU patients (p < 0.0001), except tau-methylhistidine and phenylalanine. WBP of most AA were significantly (p < 0.0001) higher with increases in glutamate (160%), glutamine (46%), and essential AA. Remarkably, net protein breakdown was lower. There were only weak relationships between AA concentrations and WBP. Critically ill ICU patients (SOFA 8-16) had lower values for phase angle (p = 0.0005) and small reductions of most plasma AA concentrations, but higher tau-methylhistidine (p = 0.0223) and hydroxyproline (p = 0.0028). Remarkably, the WBP of glutamate and glutamine were lower (p < 0.05), as was their clearance, but WBP of tau-methylhistidine (p = 0.0215) and hydroxyproline (p = 0.0028) were higher. Our study in critically ill ICU patients shows that comprehensive metabolic phenotyping was able to reveal severe disturbances in specific AA pathways, in a disease severity dependent way. This information may guide improving nutritional compositions to improve the health of the critically ill patient. CLINICAL TRIAL REGISTRY: Data are from the baseline measurements of study NCT02770092 (URL: https://clinicaltrials.gov/ct2/show/NCT02770092) and NCT03628365 (URL: https://clinicaltrials.gov/ct2/show/NCT03628365).

Inhibition of cyclooxygenase-2 expression and prostaglandin E2 production in chondrocytes by avocado soybean unsaponifiables and epigallocatechin gallate.

OBJECTIVE: To evaluate the anti-inflammatory effect of the combination of avocado soybean unsaponifiables (ASU) and epigallocatechin gallate (EGCG) on cyclooxygenase-2 (COX-2) expression and prostaglandin E(2) (PGE(2)) production in cytokine-activated equine chondrocytes. METHODS: Production of type II collagen and aggrecan was verified by immunohistochemistry and Western blot. Chondrocytes were incubated with: (1) control media alone, (2) ASU (4 microg/ml; 8.3 microg/ml), (3) EGCG (4, 40, 400 ng/ml), or (4) the combination of ASU and EGCG for 24h. Cells were next incubated with control medium alone or with IL-1beta (10 ng/ml) and TNF-alpha (1 ng/ml). COX-2 gene expression by real-time PCR analysis and NF-kappaB nuclear translocation by immunohistochemistry were performed after 1h of incubation. PGE(2) production was determined by immunoassay after 24h of incubation. RESULTS: Equine chondrocytes responded to cytokine activation by up-regulated gene expression of COX-2 and increased PGE(2) production. Activation was associated with NF-kappaB translocation. Individually, ASU and EGCG marginally inhibited COX-2 expression and PGE(2) production in activated chondrocytes. In contrast, the combination of ASU and EGCG reduced COX-2 expression close to non-activated control levels and significantly inhibited PGE(2) production. These reductions were statistically greater than those of ASU or EGCG alone. The inhibition of COX-2 expression and PGE(2) production was associated with inhibition of NF-kappaB translocation. CONCLUSION: The present study demonstrates that the anti-inflammatory activity of ASU and EGCG is potentiated when used in combination. This combination may offer an attractive supplement or alternative to non-steroidal anti-inflammatory drugs (NSAIDs) in the management of osteoarthritis.

Non-canonical Wnt signalling regulates scarring in biliary disease via the planar cell polarity receptors.

The number of patients diagnosed with chronic bile duct disease is increasing and in most cases these diseases result in chronic ductular scarring, necessitating liver transplantation. The formation of ductular scaring affects liver function; however, scar-generating portal fibroblasts also provide important instructive signals to promote the proliferation and differentiation of biliary epithelial cells. Therefore, understanding whether we can reduce scar formation while maintaining a pro-regenerative microenvironment will be essential in developing treatments for biliary disease. Here, we describe how regenerating biliary epithelial cells express Wnt-Planar Cell Polarity signalling components following bile duct injury and promote the formation of ductular scars by upregulating pro-fibrogenic cytokines and positively regulating collagen-deposition. Inhibiting the production of Wnt-ligands reduces the amount of scar formed around the bile duct, without reducing the development of the pro-regenerative microenvironment required for ductular regeneration, demonstrating that scarring and regeneration can be uncoupled in adult biliary disease and regeneration.

Single-Step Self-Assembly and Physical Crosslinking of PEGylated Chitosan Nanoparticles by Tannic Acid.

Chitosan-based nanoparticles are promising materials for potential biomedical applications. We used Flash NanoPrecipitation as a rapid, scalable, single-step method to achieve self-assembly of crosslinked chitosan nanoparticles. Self-assembly was driven by electrostatic interactions, hydrogen bonding, and hydrophobic interactions; tannic acid served to precipitate chitosan to seed nanoparticle formation and crosslink the chitosan to stabilize the resulting particles. The size of the nanoparticles can be tuned by varying formulation parameters including the total solids concentration and block copolymer to core mass ratio. We demonstrated that hydrophobic moieties can be incorporated into the nanoparticle using a lipophilic fluorescent dye as a model system.

Structural connectivity and risk for anhedonia after trauma: A prospective study and replication.

Anhedonia emerges in some people after psychological trauma, reflected by a loss of interest, diminished affect, and detachment. Structural abnormalities in specific neural pathways at the time of trauma may influence the development of these posttraumatic anhedonia (PTA) symptoms. In this prospective study, we determined whether white matter connectivity at around one month post-trauma predicts PTA and other PTSD symptoms at six months post-trauma. Thirty men and women aged 19-62 were recruited from the emergency department of a Level I trauma center. Participants received diffusion tensor imaging at approximately one month post-trauma and clinical assessments at one and six months post-trauma. Probabilistic tractography was used to examine connectivity of select pathways. A replication sample (N = 57) in an independent, cross-sectional dataset of traumatized women was similarly analyzed. Logistic regression results indicated that, after accounting for early PTSD symptoms (at one month) and other clinical risk factors, the integrity of the uncinate fasciculus (UF) uniquely predicted the presence of PTA at six months post-trauma (Beta = -225.6, p < .05). Together, these factors contributed to 76% of the variance in PTA. Integrity of the UF also predicted re-experiencing PTSD symptoms at six months post-trauma. These results were supported in our replication analyses. Our findings indicate that the integrity of the UF around 1 month post-trauma affects vulnerability for the development of anhedonic PTSD symptoms as well as re-experiencing symptoms. Connectivity of this amygdala-ventromedial prefrontal pathway appears to be a salient predictor of anhedonia, above and beyond clinical risk factors.

Cognitive and neural facets of dissociation in a traumatized population.

Dissociative phenomena are frequently experienced by psychologically traumatized people. However, little is known about the cognitive profiles of highly dissociative traumatized individuals, and corresponding patterns of neural connectivity when attentional networks are engaged in the context of emotion. One hundred seventeen traumatized women completed the multiscale dissociation inventory (MDI) and neuropsychological testing; MDI scores were used to classify high- and low-dissociative participants. Forty-six participants also underwent fMRI during performance of an attentional control task that incorporates emotionally distracting images (Affective Number Stroop; ANS). Compared to low-dissociative participants, high-dissociative participants demonstrated better performance on an executive functioning task (F1,111 = 4.64, p = .03), worse performance on a task of visual memory (F1,111 = 9.52, p = .003), and similar performance on all other neuropsychological measures. In addition, dissociative symptoms were negatively correlated with functional connectivity between the amygdala and right anterior insula in response to trauma-related ANS trials. These findings indicate that highly dissociative traumatized people experience difficulties with attentional control in the context of emotionally evocative stimuli, but in a neutral context, their overall cognitive profiles are similar to low-dissociative people. Highly dissociative participants also demonstrated weaker connectivity between the amygdala and insula in response to trauma-relevant images. Evocative, trauma-relevant stimuli appear to disrupt neutral networks involved with attention to salient cues and interoception in highly dissociative traumatized individuals. (PsycINFO Database Record (c) 2019 APA, all rights reserved).