ZFYVE21 promotes endothelial nitric oxide signaling and vascular barrier function in the kidney during aging.

ZFYVE21 is an ancient, endosome-associated protein that is highly expressed in endothelial cells (ECs) but whose function(s) in vivo are undefined. Here, we identified ZFYVE21 as an essential regulator of vascular barrier function in the aging kidney. ZFYVE21 levels significantly decline in ECs in aged human and mouse kidneys. To investigate attendant effects, we generated EC-specific Zfyve21-/- reporter mice. These knockout mice developed accelerated aging phenotypes including reduced endothelial nitric oxide (ENOS) activity, failure to thrive, and kidney insufficiency. Kidneys from Zfyve21 EC-/- mice showed interstitial edema and glomerular EC injury. ZFYVE21-mediated phenotypes were not programmed developmentally as loss of ZFYVE21 in ECs during adulthood phenocopied its loss prenatally, and a nitric oxide donor normalized kidney function in adult hosts. Using live cell imaging and human kidney organ cultures, we found that in a GTPase Rab5- and protein kinase Akt-dependent manner, ZFYVE21 reduced vesicular levels of inhibitory caveolin-1 and promoted transfer of Golgi-derived ENOS to a perinuclear Rab5+ vesicular population to functionally sustain ENOS activity. Thus, our work defines a ZFYVE21- mediated trafficking mechanism sustaining ENOS activity and demonstrates the relevance of this pathway for maintaining kidney function with aging.

Prospective Relations between Life Stress, Emotional Clarity, and Suicidal Ideation in an Adolescent Clinical Sample.

OBJECTIVE: Although life stress has been linked to adolescent suicidal ideation, most past research has been cross-sectional, and potential processes characterizing this relation remain unclear. One possibility may be a lack of emotional clarity. Informed by stress generation, the current study examined prospective relations between episodic life stress, lack of emotional clarity, and suicidal ideation in an adolescent clinical sample. METHODS: The sample consisted of 180 youths (Mage = 14.89; SD = 1.35; 71.7% female; 78.9% White; 43.0% sexual minority) recruited from a psychiatric inpatient facility. Suicidal ideation severity was assessed at baseline and 18-month follow-up. Lack of emotional clarity and life stress were assessed at baseline, as well as 6-, and 12-month follow-ups. Two random-intercepts cross-lagged panel models were created to estimate within-person relations for variables of interest. RESULTS: At the within-person level, lack of emotional clarity at baseline predicted greater 6-month impact of interpersonal dependent stressors (b = 0.29, p = .012, 95% CI [0.07, 0.52]), which subsequently predicted a greater 12-month lack of emotional clarity (b = 0.41, p = .005, 95% CI [0.12, 0.70]). Next, a 12-month lack of emotional clarity but not interpersonal dependent stress, predicted greater 18-month suicidal ideation (b = 0.81, p = .006, 95% CI [0.23, 1.30]; R2 = .24, p < .001). No significant relations were found for the lack of emotional clarity and independent stress. CONCLUSIONS: Results support the stress generation hypothesis and suggest that future research should be conducted evaluating whether bolstering youth's understanding of their emotional experiences may reduce subsequent suicidal ideation.

The living donor evaluation as a life-saving event.

BACKGROUND: As a population, living kidney donors have a longer life expectancy than the general population. This is generally thought to be an artifact of selection, as only healthy individuals are allowed to donate, and the operative mortality and risk of subsequent renal failure are very low. However, there may also be an additional benefit to the process, as the donor evaluation may uncover an early occult cancer or a potentially serious medical problem. While these problems may preclude donation, they may be lifesaving, as they are likely to be diagnosed and treated before the donor develops symptoms. PATIENTS AND METHODS: We looked at the incidence of occult cancer and other previously undiagnosed medical problems including renal disease, diabetes, hypertension, cardiac disease, and hepatitis C, in individuals volunteering to become a kidney donor at our center who proceeded with the evaluation between January 1, 1996 and May 31, 2011. RESULTS: Of 4088 potential donors, 19 (.46%) were discovered to have an unsuspected cancer, and 286 (7%) were found to have a previously undiagnosed medical problem. CONCLUSIONS: The living donor evaluation may lead to the early diagnosis of a life-threatening illness. This should be considered as one of the potential benefits of living donation.

Serum anti-GM2 and anti-GalNAc-GD1a ganglioside IgG antibodies are biomarkers for immune-mediated polyneuropathies in cats.

Recent work identified anti-GM2 and anti-GalNAc-GD1a IgG ganglioside antibodies as biomarkers in dogs clinically diagnosed with acute canine polyradiculoneuritis, in turn considered a canine equivalent of Guillain-Barré syndrome. This study aims to investigate the serum prevalence of similar antibodies in cats clinically diagnosed with immune-mediated polyneuropathies. The sera from 41 cats clinically diagnosed with immune-mediated polyneuropathies (IPN), 9 cats with other neurological or neuromuscular disorders (ONM) and 46 neurologically normal cats (CTRL) were examined for the presence of IgG antibodies against glycolipids GM1, GM2, GD1a, GD1b, GalNAc-GD1a, GA1, SGPG, LM1, galactocerebroside and sulphatide. A total of 29/41 IPN-cats had either anti-GM2 or anti-GalNAc-GD1a IgG antibodies, with 24/29 cats having both. Direct comparison of anti-GM2 (sensitivity: 70.7%; specificity: 78.2%) and anti-GalNAc-GD1a (sensitivity: 70.7%; specificity: 70.9%) antibodies narrowly showed anti-GM2 IgG antibodies to be the better marker for identifying IPN-cats when compared to the combined ONM and CTRL groups (P = .049). Anti-GA1 and/or anti-sulphatide IgG antibodies were ubiquitously present across all sample groups, whereas antibodies against GM1, GD1a, GD1b, SGPG, LM1 and galactocerebroside were overall only rarely observed. Anti-GM2 and anti-GalNAc-GD1a IgG antibodies may serve as serum biomarkers for immune-mediated polyneuropathies in cats, as previously observed in dogs and humans.

Electrochemical Kinetics and Detection of Paracetamol by Stevensite-Modified Carbon Paste Electrode in Biological Fluids and Pharmaceutical Formulations.

Paracetamol (PCT), or acetaminophen, is an important drug used worldwide for various clinical purposes. However, the excessive or indiscriminate use of PCT can provoke liver and kidney dysfunction; hence, it is essential to determine the amount of this target in biological samples. In this work, we develop a quick, simple, and sensitive voltammetric method using chemically modified electrodes to determine PCT in complex matrices, including human serum and commercial solid formulations. We modify the carbon paste electrode with stevensite monoclinic clay mineral (Stv-CPE), using cyclic voltammetry, differential pulse voltammetry, and electrochemical impedance spectroscopy to characterise and detect PCT. The kinetics study provides a better electrochemical characterisation of the electrode behaviour, finding the detection and quantitation limits of 0.2 µM and 0.5 µM under favourable conditions. Further, the best linear working concentration range is 0.6-100 µM for PCT, applying the proposed method to the quantitative determination of PCT content in reference tablet formulations and biological samples for validation.

Domestic Dogs as Sentinels for West Nile Virus but not Aedes-borne Flaviviruses, Mexico.

We tested 294 domestic pet dogs in Mexico for neutralizing antibodies for mosquito-borne flaviviruses. We found high (42.6%) exposure to West Nile virus in Reynosa (northern Mexico) and low (1.2%) exposure in Tuxtla Gutierrez (southern Mexico) but very limited exposure to Aedes-borne flaviviruses. Domestic dogs may be useful sentinels for West Nile virus.

QM/MM Energy Decomposition Using the Interacting Quantum Atoms Approach.

The interacting quantum atoms (IQA) method decomposes the quantum mechanical (QM) energy of a molecular system in terms of one- and two-center (atomic) contributions within the context of the quantum theory of atoms in molecules. Here, we demonstrate that IQA, enhanced with molecular mechanics (MM) and Poisson-Boltzmann surface-area (PBSA) solvation methods, is naturally extended to the realm of hybrid QM/MM methodologies, yielding intra- and inter-residue energy terms that characterize all kinds of covalent and noncovalent bonding interactions. To test the robustness of this approach, both metal-water interactions and QM/MM boundary artifacts are characterized in terms of the IQA descriptors derived from QM regions of varying size in Zn(II)- and Mg(II)-water clusters. In addition, we analyze a homologous series of inhibitors in complex with a matrix metalloproteinase (MMP-12) by carrying out QM/MM-PBSA calculations on their crystallographic structures followed by IQA energy decomposition. Overall, these applications not only show the advantages of the IQA QM/MM approach but also address some of the challenges lying ahead for expanding the QM/MM methodology.

Mitochondrial fission factor (MFF) frameshift variant in Bullmastiffs with mitochondrial fission encephalopathy.

Familial cerebellar ataxia with hydrocephalus in Bullmastiffs was described almost 40 years ago as a monogenic autosomal recessive trait. We investigated two young Bullmastiffs showing similar clinical signs. They developed progressive gait and behavioural abnormalities with an onset at around 6 months of age. Neurological assessment was consistent with a multifocal brain disease. Magnetic resonance imaging of the brain showed intra-axial bilateral symmetrical focal lesions localised to the cerebellar nuclei. Based on the juvenile age, nature of neurological deficits and imaging findings, an inherited disorder of the brain was suspected. We sequenced the genome of one affected Bullmastiff. The data were compared with 782 control genomes of dogs from diverse breeds. This search revealed a private homozygous frameshift variant in the MFF gene in the affected dog, XM_038574000.1:c.471_475delinsCGCTCT, that is predicted to truncate 55% of the wild type MFF open reading frame, XP_038429928.1: p.(Glu158Alafs*14). Human patients with pathogenic MFF variants suffer from 'encephalopathy due to defective mitochondrial and peroxisomal fission 2'. Archived samples from two additional affected Bullmastiffs related to the originally described cases were obtained. Genotypes in a cohort of four affected and 70 unaffected Bullmastiffs showed perfect segregation with the disease phenotype. The available data together with information from previous disease reports allow classification of the investigated MFF frameshift variant as pathogenic and probably causative defect of the observed neurological phenotype. In analogy to the human phenotype, we propose to rename this disease 'mitochondrial fission encephalopathy (MFE)'.

Computation of Gait Parameters in Post Stroke and Parkinson's Disease: A Comparative Study Using RGB-D Sensors and Optoelectronic Systems.

The accurate and reliable assessment of gait parameters is assuming an important role, especially in the perspective of designing new therapeutic and rehabilitation strategies for the remote follow-up of people affected by disabling neurological diseases, including Parkinson's disease and post-stroke injuries, in particular considering how gait represents a fundamental motor activity for the autonomy, domestic or otherwise, and the health of neurological patients. To this end, the study presents an easy-to-use and non-invasive solution, based on a single RGB-D sensor, to estimate specific features of gait patterns on a reduced walking path compatible with the available spaces in domestic settings. Traditional spatio-temporal parameters and features linked to dynamic instability during walking are estimated on a cohort of ten parkinsonian and eleven post-stroke subjects using a custom-written software that works on the result of a body-tracking algorithm. Then, they are compared with the "gold standard" 3D instrumented gait analysis system. The statistical analysis confirms no statistical difference between the two systems. Data also indicate that the RGB-D system is able to estimate features of gait patterns in pathological individuals and differences between them in line with other studies. Although they are preliminary, the results suggest that this solution could be clinically helpful in evolutionary disease monitoring, especially in domestic and unsupervised environments where traditional gait analysis is not usable.

Posttraumatic stress disorder symptom clusters, suicidal ideation, and social support in a clinical adolescent sample.

Posttraumatic stress disorder (PTSD) is a risk factor for adolescent suicidal ideation (SI). This study explored the relation between PTSD symptom clusters and SI, and whether social support moderates this association, in a cross-sectional, adolescent, clinical sample (N = 125). We hypothesized that each cluster would be positively associated with SI severity and that social support would buffer these associations. Only the persistent avoidance cluster was significantly associated with SI severity. Further, social support moderated this association. Results highlight the positive association between persistent avoidance symptoms of PTSD and SI and suggest that bolstering social support serves a protective function.

Sexual Identity and its Association with Trajectories of Depressive Symptoms and Emotion Regulation Difficulties from Early to Middle Adolescence.

Few studies have examined how changes in sexual identity impact trajectories of depressive symptoms and emotion regulation difficulties. The current study addresses this gap in the literature by examining these associations over a three-year period in a community sample of adolescents (N = 177; Mage = 12.56; SD = 0.60; nmale = 95). Multilevel modeling revealed that youth who consistently held sexual minority identities from early to middle adolescence-but not youth with inconsistent sexual identity-demonstrated increases in depressive symptoms and emotion regulation difficulties relative to their heterosexual peers. Findings suggest that treatments that bolster emotion regulation abilities and address depressive symptoms may be of particular benefit to youth with consistent sexual minority identities from early to middle adolescence.

Patient Navigation to Improve Early Access to Supportive Care for Patients with Advanced Cancer in Resource-Limited Settings: A Randomized Controlled Trial.

BACKGROUND: The early integration of supportive care in oncology improves patient-centered outcomes. However, data are lacking regarding how to achieve this in resource-limited settings. We studied whether patient navigation increased access to multidisciplinary supportive care among Mexican patients with advanced cancer. MATERIALS AND METHODS: This randomized controlled trial was conducted between August 2017 and April 2018 at a public hospital in Mexico City. Patients aged ≥18 years with metastatic tumors ≤6 weeks from diagnosis were randomized (1:1) to a patient navigation intervention or usual care. Patients randomized to patient navigation received personalized supportive care from a navigator and a multidisciplinary team. Patients randomized to usual care obtained supportive care referrals from treating oncologists. The primary outcome was the implementation of supportive care interventions at 12 weeks. Secondary outcomes included advance directive completion, supportive care needs, and quality of life. RESULTS: One hundred thirty-four patients were randomized: 67 to patient navigation and 67 to usual care. Supportive care interventions were provided to 74% of patients in the patient navigation arm versus 24% in usual care (difference 0.50, 95% confidence interval [CI] 0.34-0.62; p < .0001). In the patient navigation arm, 48% of eligible patients completed advance directives, compared with 0% in usual care (p < .0001). At 12 weeks, patients randomized to patient navigation had less moderate/severe pain (10% vs. 33%; difference 0.23, 95% CI 0.07-0.38; p = .006), without differences in quality of life between arms. CONCLUSION: Patient navigation improves access to early supportive care, advance care planning, and pain for patients with advanced cancer in resource-limited settings. IMPLICATIONS FOR PRACTICE: The early implementation of supportive care in oncology is recommended by international guidelines, but this might be difficult to achieve in resource-limited settings. This randomized clinical trial including 134 Mexican patients with advanced cancer demonstrates that a multidisciplinary patient navigation intervention can improve the early access to supportive and palliative care interventions, increase advance care planning, and reduce symptoms compared with usual oncologist-guided care alone. These results demonstrate that patient navigation represents a potentially useful solution to achieve the adequate implementation of supportive and palliative care in resource-limited settings globally.

An evaluation of the safety and preliminary efficacy of peri- and post-operative treprostinil in preventing ischemia and reperfusion injury in adult orthotopic liver transplant recipients.

BACKGROUND: Orthotopic liver transplantation (OLT) is the only treatment option for various end-stage liver diseases. Ischemia and reperfusion (I/R) injury is one of the unavoidable complications/conditions in OLT. In 2019, a total of 8896 livers were transplanted of which >94% organs were procured from deceased donors. An increase in the use of extended criteria donor (ECD) livers for transplantation further unraveled the role of hepatic I/R injury on short-term and long-term graft outcomes. Despite promising outcomes with the use of antioxidants, free radical scavengers, and vasodilators; I/R-mediated liver injury persists and significantly influences the overall clinical outcomes. Treprostinil, a synthetic prostacyclin I2  (PGI2 ) analog, due to its vasodilatory property, antiplatelet activity, and its ability to downregulate pro-inflammatory cytokines can potentially minimize I/R injury. AIM: We investigated the safety and preliminary efficacy of continuous intravenous infusion of treprostinil in liver transplant recipients in a prospective, single-center, non-randomized, interventional study. MATERIAL AND METHODS: This was a dose escalation (3 + 3 design) phase 1/2 study. Deceased donor liver transplant recipients received 5 ng/kg/min for two days, or 2.5, 5, and 7.5 ng/min/kg for 5 days as a continuous infusion. Multiple blood samples were collected for biochemical parameter assessment and for measuring treprostinil levels. Indocyanine green plasma disappearance rate was used as a measure of hepatic functional capacity. RESULTS: Subjects tolerated continuous infusion of treprostinil up to 5 ng/kg/min for 120 h with no occurrence of primary graft non-function (PNF), minimized need for ventilation support, reduced hospitalization time, 100% graft and patient survival, and improved hepatobiliary excretory function comparable to normal healthy adults. DISCUSSION: Treprostinil can be administered to liver transplant patients safely during the perioperative period. CONCLUSION: Based on this phase 1/2 study, further efficacy studies of treprostinil in preventing I/R injury of liver should be conducted to potentially increase the number of livers available for transplantation.

Clinical Outcomes of Transcatheter Arterial Embolization for Secondary Stiff Shoulder.

PURPOSE: To assess the clinical outcomes of transcatheter arterial embolization (TAE) for secondary stiff shoulder (SSS). MATERIALS AND METHODS: This is a retrospective analysis of prospectively collected data performed between January 2017 and December 2019. This study comprised 25 patients (20 women and 5 men; median age, 49 years; range 27-59) with SSS resistant to conservative management during at least 3 months. The median time of stiffness was 12 months. The etiology of SSS was postoperative in 14 patients (56%) and posttraumatic in the remaining 11 patients (44%). Periods of immobilization in all patients were associated. TAE was performed, and technical aspects, adverse events, changes for pain, and physical examination before and 6 months after TAE were assessed. RESULTS: Abnormal vessels were observed in 20 of 25 (80%) of the procedures. Transitory cutaneous erythema was noted in 4 patients treated after TAE. Significant differences were observed in the median pain visual analog scale reduction between before and 6 months after TAE (8 vs 2, P < .001). Shoulder mobility significantly improved in both flexion and abduction degrees between before and at 6 months after TAE in (70° vs 150°; P < .001). No symptoms of recurrence appeared. CONCLUSIONS: TAE can result in pain reduction and mobility improvement in patients with SSS refractory to conservative therapy.

Adolescent depressed mood and difficulties with emotion regulation: Concurrent trajectories of change.

INTRODUCTION: Adolescent depression is a significant mental health concern. Emotion regulation difficulties have been associated with subsequent depressive symptoms, though different facets of emotion regulation are rarely compared. This study examined the degree to which trajectories of change in different facets of emotion regulation (goal-directed behavior, impulse control, and regulation strategies) and depressive symptoms were associated across twelve months in a clinical adolescent sample. METHODS: Participants included 110 adolescents from the US who were enrolled in a randomized trial that tested a cognitive-behavioral treatment for youth with co-occurring mental health and substance use concerns (Mage = 15.71 years; 57.3% male). Assessments were conducted at baseline, 3-, 6-, and 12-month follow-ups. Three separate bivariate latent basis growth curve analyses were conducted. Correlations between latent intercepts and latent slopes, as well as overall model fit, were examined. RESULTS: Impulse control and goal-directed behavior were each associated with depressive symptoms at baseline. Additionally, change in impulse control over time was significantly associated with change in depressive symptoms. However, the same was not true for goal-directed behavior. Overall fit indices for models of emotion regulation strategies were below acceptable levels and thus could not be interpreted. CONCLUSIONS: Findings from the present study indicate that adolescents' depressive symptoms appear to improve as their perceived ability to control impulses improves. These results suggest that addressing impulse control difficulties may be an important step in treating adolescent depression and co-occurring disorders.

Depression-related emotional problems mediate the relation between hopelessness and suicidal ideation severity.

OBJECTIVE: Cross-sectional research with adult samples suggests that hopelessness may indirectly affect suicidal ideation (SI) through overall depressive symptom severity. However, particular depressive symptom constellations, rather than overall symptoms, may underlie the association between hopelessness and SI. Yet, the cross-sectional nature of these studies precludes examination of the temporal associations among these constructs. METHODS: Using path analysis, the present study examined whether depression-related emotional problems mediate the relation between hopelessness and SI in a clinical sample of 110 adolescents over a 6-month period. The specificity of depression-related emotional problems as a mediator was also evaluated. RESULTS: After accounting for covariates, results supported the specificity of 3-month depression-related emotional problems as a mediator of the association between baseline levels of hopelessness and 6-month SI. CONCLUSION: Results suggest that treatment targeted specifically at hopelessness may help reduce depression-related emotional problems and lower SI, and ultimately, adolescent suicide risk.

Magnetic resonance imaging findings and clinical management of suspected intracranial hypovolemia after transfrontal craniotomy in a dog.

OBJECTIVE: To report the diagnosis and clinical management of a case of suspected intracranial hypovolemia (IH) in a dog after resection of a large fronto-olfactory chordoid meningioma. STUDY DESIGN: Clinical case report. ANIMAL: One 8-year-old border collie with forebrain neurological signs caused by a fronto-olfactory extra-axial mass diagnosed by using MRI. METHODS: The dog underwent bilateral transfrontal craniotomy for excision of the mass by using ultrasonic aspiration. Immediate postsurgical MRI revealed complete gross resection with no evidence of early-onset complications such as edema, hemorrhage, mass effect, or pneumoencephalus. However, diffuse symmetric meningeal thickening and contrast enhancement were noted. No complications were noted during surgery or while under anesthesia. RESULTS: Neurological deterioration was observed postoperatively. No abnormalities were detected systemically. Thus, early MRI-confirmed findings and neurological deterioration were suspected to be caused by IH. Conservative treatment consisting of bed rest, gabapentin, and intravenous theophylline was then initiated in addition to steroids, antiepileptic drugs, and antibiotics. A gradual neurological improvement was observed, and the dog was discharged completely ambulatory with moderate proprioceptive ataxia 15 days after surgery. CONCLUSION: The clinical and MRI-confirmed findings reported here are consistent with IH, a well-described syndrome in man. This is the first report of a dog with MRI-confirmed findings consistent with IH describing subsequent response to medical management. CLINICAL SIGNIFICANCE: Intracranial hypovolemia after craniotomy should be considered when there is neurological deterioration and characteristic MRI-confirmed findings.

Lumbosacral intervertebral disk extrusions in 13 dogs.

OBJECTIVE: To describe the clinical presentation, magnetic resonance imaging (MRI) findings, and outcome of dogs treated surgically for lumbosacral intervertebral disk extrusion (IVDE). STUDY DESIGN: Retrospective study. ANIMALS: Thirteen dogs. METHODS: Records and MRI studies of dogs with intraoperatively confirmed lumbosacral IVDE were reviewed. MRI features of thoracolumbar IVDE were applied to all cases. Postoperative outcome was subjectively assessed as excellent, good, or poor. RESULTS: All dogs had an acute or subacute onset of lumbosacral pain and nerve root signature. Seven dogs had neurological deficits. MRI revealed lateralized herniated disk material and partial to complete disk degeneration in all cases; the extradural material extended cranial and/or caudally from the disk space in 10 cases. All dogs underwent L7-S1 dorsal laminectomy and removal of extruded disk material. In six dogs, surgery was complicated by inflammatory changes, including one case of epidural steatitis. On reexamination 4-6 weeks postsurgery, outcome was judged as excellent in 11 dogs and poor in the remaining 2 due to contralateral nerve root signature in one case and nonambulatory paraparesis and urinary incontinence in the case with steatitis. CONCLUSION: Lumbosacral IVDE in dogs was characterized by acute/subacute onset of lumbosacral pain and nerve root signature and lateralized and often dispersed extradural material over a degenerated L7-S1 intervertebral disk on MRI. Early decompressive dorsal laminectomy generally resulted in excellent clinical outcome. CLINICAL SIGNIFICANCE: Observation of these clinical and imaging features in dogs should prompt clinical suspicion of lumbosacral IVDE.

High-Frequency Heart Rate Variability and Emotion-Driven Impulse Control Difficulties During Adolescence: Examining Experienced and Expressed Negative Emotion as Moderators.

Emotion-driven impulse control difficulties are associated with negative psychological outcomes. Extant research suggests that high frequency heart rate variability (HF-HRV) may be indicative of emotion-driven impulse control difficulties and potentially moderated by negative emotion. In the current study, 248 eleven- to 14-year-olds and their parent engaged in a negatively emotionally arousing conflict task at Time 1. Adolescents' HF-HRV and negative emotional expression and experience were assessed before, during, and/or after the task. Adolescents reported on their levels of emotion-driven impulse control difficulties at Time 1 and one year later. Results revealed that higher levels of HF-HRV reactivity (i.e., higher HF-HRV augmentation) predicted higher levels of emotion-driven impulse control difficulties one year later among adolescents who experienced higher negative emotion. These findings suggest that negative emotional context should be considered when examining HF-HRV reactivity as a risk factor for emotion-driven impulse control difficulties and associated outcomes.

Development of Ectopic Livers by Hepatocyte Transplantation Into Swine Lymph Nodes.

Orthotopic liver transplantation continues to be the only effective therapy for patients with end-stage liver disease. Unfortunately, many of these patients are not considered transplant candidates, lacking effective therapeutic options that would address both the irreversible progression of their hepatic failure and the control of their portal hypertension. In this prospective study, a swine model was exploited to induce subacute liver failure. Autologous hepatocytes, isolated from the left hepatic lobe, were transplanted into the mesenteric lymph nodes (LNs) by direct cell injection. At 30-60 days after transplantation, hepatocyte engraftment in LNs was successfully identified in all transplanted animals with the degree of ectopic liver mass detected being proportional to the induced native liver injury. These ectopic livers developed within the LNs showed remarkable histologic features of swine hepatic lobules, including the formation of sinusoids and bile ducts. On the basis of our previous tyrosinemic mouse model and the present pig models of induced subacute liver failure, the generation of auxiliary liver tissue using the LNs as hepatocyte engraftment sites represents a potential therapeutic approach to supplement declining hepatic function in the treatment of liver disease.