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A portal system is one, which by definition, begins and ends with capillaries. The major portal system in humans is one in which the capillaries originate in the mesentery of the intestines and spleen and end in the hepatic sinusoids. Capillaries of the superior mesenteric and splenic veins supply the portal vein with a nutrient- and hormone-rich blood supply. The partially oxygenated portal venous blood supplements the oxygenated hepatic arterial flow to give the liver unique protection against hypoxia. Blood flow from the hepatic artery and portal vein is well coordinated to maintain consistent flow and explains the ability of the liver to withstand thrombosis of either of these major vascular structures. This well-regulated blood flow in conjunction with the very low resistance found in the portal system results in a low baseline portal pressure in healthy individuals.
Inherited cholestasis of hepatocellular origin has long been described in the neonate or during the first year of life . Many of these infants were categorized as having idiopathic neonatal hepatitis after biliary atresia, metabolic diseases, and congenital infections were excluded . The prognosis in familial cholestasis was poor compared with sporadic cholestasis that sometimes had an identifiable etiology. As the clinical and genotypic heterogeneity of these inherited disorders has become apparent, it is now recognized that patients may present initially and progress to end-stage liver disease at ages ranging from infancy to adulthood [3, 4].There may be significant overlap in clinical features such as intense pruritus and a low serum concentration of gamma-glutamyltransferase (GGT). The histopathology, immunohistochemical staining, and hepatic ultrastructure may provide additional diagnostic clues as to the underlying defect. However, next generation sequencing including use of targeted gene panels has proven of great value in rapidly and reliably discriminating cholestatic diseases of childhood, may suggest therapy with varying success based on the genotype of the patient, and has advanced our understanding of molecular mechanisms of bile secretion and acquired cholestasis . It is not surprising that, so far, mutations in three genes encoding ATP-dependent transport proteins localized to the canalicular membrane that result in progressive cholestasis and liver injury have been discovered. The features of these disorders are compared in Table 13.1. Other genes encoding proteins involved in membrane transport, vesicular trafficking, and integrity of the cell junction may also be mutated in some patients. Mutations in the genes responsible for PFIC may be found in some adults with cryptogenic cholestasis and women with cholestasis of pregnancy including in the heterozygous state . Owing to an immaturity of hepatic excretory function, cholestasis may occasionally occur in inherited diseases because of systemic illness rather than a primary defect in the liver (see Table 9.1). These disorders will not be considered in this review.
Attentional bias to threat has been implicated as a cognitive mechanism in anxiety disorders for youth. Yet, prior studies documenting this bias have largely relied on a method with questionable reliability (i.e. dot-probe task) and small samples, few of which included adolescents. The current study sought to address such limitations by examining relations between anxiety – both clinically diagnosed and dimensionally rated – and attentional bias to threat.
The study included a community sample of adolescents and employed eye-tracking methodology intended to capture possible biases across the full range of both automatic (i.e. vigilance bias) and controlled attentional processes (i.e. avoidance bias, maintenance bias). We examined both dimensional anxiety (across the full sample; n = 215) and categorical anxiety in a subset case-control analysis (n = 100) as predictors of biases.
Findings indicated that participants with an anxiety disorder oriented more slowly to angry faces than matched controls. Results did not suggest a greater likelihood of initial orienting to angry faces among our participants with anxiety disorders or those with higher dimensional ratings of anxiety. Greater anxiety severity was associated with greater dwell time to neutral faces.
This is the largest study to date examining eye-tracking metrics of attention to threat among healthy and anxious youth. Findings did not support the notion that anxiety is characterized by heightened vigilance or avoidance/maintenance of attention to threat. All effects detected were extremely small. Links between attention to threat and anxiety among adolescents may be subtle and highly dependent on experimental task dimensions.
Years of sport participation (YoP) is conventionally used to estimate cumulative repetitive head impacts (RHI) experienced by contact sport athletes. The relationship of this measure to other estimates of head impact exposure and the potential associations of these measures with neurobehavioral functioning are unknown. We investigated the association between YoP and the Head Impact Exposure Estimate (HIEE), and whether associations between the two estimates of exposure and neurobehavioral functioning varied.
Former American football players (N = 58; age = 37.9 ± 1.5 years) completed in-person evaluations approximately 15 years following sport discontinuation. Assessments consisted of neuropsychological assessment and structured interviews of head impact history (i.e., HIEE). General linear models were fit to test the association between YoP and the HIEE, and their associations with neurobehavioral outcomes.
YoP was weakly correlated with the HIEE, p = .005, R2 = .13. Higher YoP was associated with worse performance on the Symbol Digit Modalities Test, p = .004, R2 = .14, and Trail Making Test-B, p = .001, R2 = .18. The HIEE was associated with worse performance on the Delayed Recall trial of the Hopkins Verbal Learning Test-Revised, p = .020, R2 = .09, self-reported cognitive difficulties (Neuro-QoL Cognitive Function), p = .011, R2 = .10, psychological distress (Brief Symptom Inventory-18), p = .018, R2 = .10, and behavioral regulation (Behavior Rating Inventory of Executive Function for Adults), p = .017, R2 = .10.
YoP was marginally associated with the HIEE, a comprehensive estimate of head impacts sustained over a career. Associations between each exposure estimate and neurobehavioral functioning outcomes differed. Findings have meaningful implications for efforts to accurately quantify the risk of adverse long-term neurobehavioral outcomes potentially associated with RHI.
The COVID-19 pandemic has led to global shortages of N95 respirators. Reprocessing of used N95 respirators may provide a higher filtration crisis alternative, but it is unknown if effective sterilization can be achieved for a virus without impairing respirator function. We evaluated the viricidal efficacy of Bioquell vaporized hydrogen peroxide (VHP) on contaminated N95 respirators and tested the particulate particle penetration and inhalation/exhalation resistance of respirators after multiple cycles of VHP.
3M 1870 N95 respirators (3M, St. Paul, MN) were contaminated with 3 aerosolized bacteriophages: T1, T7, and Pseudomonas phage phi-6 followed by one cycle of VHP decontamination using a BQ-50 system (Bioquell, Horsham, PA). Additionally, new and unused respirators were sent to an independent laboratory, Nelson Labs (Salt Lake City, UT), for particulate filter penetration testing and inhalation/exhalation resistance after 3 and 5 cycles of VHP.
A single VHP cycle resulted in complete eradication of bacteriophage from respirators (limit of detection 10 PFU). Respirators showed acceptable limits for inhalation/exhalation resistance after 3 and 5 cycles of VHP. Respirators demonstrated a filtration efficiency >99 % after 3 cycles, but fell below 95% after 5 cycles of HPV.
Bioquell VHP demonstrated high viricidal activity for N95 respirators inoculated with aerosolized bacteriophages. Bioquell technology can be scaled for simultaneous decontamination of a large number of used but otherwise intact respirators. Reprocessing should be limited to 3 cycles due to concerns both about impact of clinical wear and tear on fit, and to decrement in filtration after 3 cycles.
Psychological attachment to political parties can bias people’s attitudes, beliefs, and group evaluations. Studies from psychology suggest that self-affirmation theory may ameliorate this problem in the domain of politics on a variety of outcome measures. We report a series of studies conducted by separate research teams that examine whether a self-affirmation intervention affects a variety of outcomes, including political or policy attitudes, factual beliefs, conspiracy beliefs, affective polarization, and evaluations of news sources. The different research teams use a variety of self-affirmation interventions, research designs, and outcomes. Despite these differences, the research teams consistently find that self-affirmation treatments have little effect. These findings suggest considerable caution is warranted for researchers who wish to apply the self-affirmation framework to studies that investigate political attitudes and beliefs. By presenting the “null results” of separate research teams, we hope to spark a discussion about whether and how the self-affirmation paradigm should be applied to political topics.
Surface energy-balance models are commonly used in conjunction with satellite thermal imagery to estimate supraglacial debris thickness. Removing the need for local meteorological data in the debris thickness estimation workflow could improve the versatility and spatiotemporal application of debris thickness estimation. We evaluate the use of regional reanalysis data to derive debris thickness for two mountain glaciers using a surface energy-balance model. Results forced using ERA-5 agree with AWS-derived estimates to within 0.01 ± 0.05 m for Miage Glacier, Italy, and 0.01 ± 0.02 m for Khumbu Glacier, Nepal. ERA-5 data were then used to estimate spatiotemporal changes in debris thickness over a ~20-year period for Miage Glacier, Khumbu Glacier and Haut Glacier d'Arolla, Switzerland. We observe significant increases in debris thickness at the terminus for Haut Glacier d'Arolla and at the margins of the expanding debris cover at all glaciers. While simulated debris thickness was underestimated compared to point measurements in areas of thick debris, our approach can reconstruct glacier-scale debris thickness distribution and its temporal evolution over multiple decades. We find significant changes in debris thickness over areas of thin debris, areas susceptible to high ablation rates, where current knowledge of debris evolution is limited.
Liver disease in children is increasing in prevalence, placing a huge burden on healthcare systems and often requiring long-term management. Offering an integrative approach to the science and clinical practice of pediatric hepatology, this is the definitive reference text for improved diagnosis and treatment strategies. In the new edition of this authoritative text, chapters have been thoroughly revised in line with major advances in the field, such as recognizing the increased frequency of fatty liver disease, and how genetic testing has the potential to establish earlier diagnoses for a variety of diseases. Disorders covered include cholestasis, metabolic disorders and hepatitis, with their presentation across the spectrum of infancy, childhood and adolescence discussed. The indications and surgical aspects of liver transplant are explained and post-transplant care is described in detail. This is a valuable resource for pediatricians, hepatologists, gastroenterologists and all clinicians involved in the care of children with liver diseases.
Subanesthetic ketamine infusion therapy can produce fast-acting antidepressant effects in patients with major depression. How single and repeated ketamine treatment modulates the whole-brain functional connectome to affect clinical outcomes remains uncharacterized.
Data-driven whole brain functional connectivity (FC) analysis was used to identify the functional connections modified by ketamine treatment in patients with major depressive disorder (MDD). MDD patients (N = 61, mean age = 38, 19 women) completed baseline resting-state (RS) functional magnetic resonance imaging and depression symptom scales. Of these patients, n = 48 and n = 51, completed the same assessments 24 h after receiving one and four 0.5 mg/kg intravenous ketamine infusions. Healthy controls (HC) (n = 40, 24 women) completed baseline assessments with no intervention. Analysis of RS FC addressed effects of diagnosis, time, and remitter status.
Significant differences (p < 0.05, corrected) in RS FC were observed between HC and MDD at baseline in the somatomotor network and between association and default mode networks. These disruptions in FC in MDD patients trended toward control patterns with ketamine treatment. Furthermore, following serial ketamine infusions, significant decreases in FC were observed between the cerebellum and salience network (SN) (p < 0.05, corrected). Patient remitters showed increased FC between the cerebellum and the striatum prior to treatment that decreased following treatment, whereas non-remitters showed the opposite pattern.
Results support that ketamine treatment leads to neurofunctional plasticity between distinct neural networks that are shown as disrupted in MDD patients. Cortico-striatal-cerebellar loops that encompass the SN could be a potential biomarker for ketamine treatment.
For decades confirmatory factor analysis (CFA) has been the preeminent method to study the underlying structure of posttraumatic stress disorder (PTSD); however, methodological limitations of CFA have led to the emergence of other analytic approaches. In particular, network analysis has become a gold standard to investigate the structure and relationships between PTSD symptoms. A key methodological limitation, however, which has significant clinical implications, is the lack of data on the potential impact of item order effects on the conclusions reached through network analyses.
The current study, involving a large sample (N = 5055) of active duty army soldiers following deployment to Iraq, assessed the vulnerability of network analyses and prevalence rate to item order effects. This was done by comparing symptom networks of the DSM-IV PTSD checklist items to these same items distributed in random order. Half of the participants rated their symptoms on traditionally ordered items and half the participants rated the same items, but in random order and interspersed between items from other validated scales. Differences in prevalence rate and network composition were examined.
The prevalence rate differed between the ordered and random item samples. Network analyses using the ordered survey closely replicated the conclusions reached in the existing network analyses literature. However, in the random item survey, network composition differed considerably.
Order effects appear to have a significant impact on conclusions reached from PTSD network analysis. Prevalence rates were also impacted by order effects. These findings have important diagnostic and clinical treatment implications.
Physicians play a critical role in preventing and treating firearm injury, although the scope of that role remains contentious and lacks systematic definition. This piece aims to utilize the fundamental principles of medical ethics to present a framework for physician involvement in firearm violence. Physicians' agency relationship with their patients creates ethical obligations grounded on three principles of medical ethics — patient autonomy, beneficence, and nonmaleficence. Taken together, they suggest that physicians ought to engage in clinical screening and treatment related to firearm violence. The principle of beneficence also applies more generally, but more weakly, to relations between physicians and society, creating nonobligatory moral ideals. Balanced against physicians' primary obligations to patient agency relationships, general beneficence suggests that physicians may engage in public advocacy to address gun violence, although they are not ethically obligated to do so. A fourth foundational principle — justice — requires that clinicians attempt to ensure that the benefits and burdens of healthcare are distributed fairly.