Miracle-dz/UniFAR-FTUs huggingface dataset:
Maternal Parenting Behaviors and Adolescent Depression: The Mediating Role of Rumination

Substantial evidence suggests that rumination is an important vulnerability factor for adolescent depression. Despite this, few studies have examined environmental risk factors that might lead to rumination and, subsequently, depression in adolescence. This study examined the hypothesis that an adverse family environment is a risk factor for rumination, such that the tendency to ruminate mediates the longitudinal association between a negative family environment and adolescent depressive symptoms. It also investigated adolescent gender as a moderator of the relationship between family environment and adolescent rumination. Participants were 163 mother–adolescent dyads. Adolescents provided self-reports of depressive symptoms and rumination across three waves of data collection (approximately at ages 12, 15, and 17 years). Family environment was measured via observational assessment of the frequency of positive and aggressive parenting behaviors during laboratory-based interactions completed by mother-adolescent dyads, collected during the first wave. A bootstrap analysis revealed a significant indirect effect of low levels of positive maternal behavior on adolescent depressive symptoms via adolescent rumination, suggesting that rumination might mediate the relationship between low levels of positive maternal behavior and depressive symptoms for girls. This study highlights the importance of positive parenting behaviors as a possible protective factor against the development of adolescent rumination and, subsequently, depressive symptoms. One effective preventive approach to improving adolescent mental health may be providing parents with psychoeducation concerning the importance of pleasant and affirming interactions with their children.
The Pathogenesis of 3 Neurotropic Flaviviruses in a Mouse Model Depends on the Route of Neuroinvasion After Viremia

Abstract Neurotropic flavivirus infection of humans results in viremia subsequently; in some cases, it causes meningitis encephalomyelitis, although the pathways from viremia to central nervous system (CNS) invasion are uncertain. Here, we intravenously infected BALB/c mice with 3 neurotropic flaviviruses, then examined the clinical manifestations and histopathologic changes. The Sofjin strain of tick-borne encephalitis virus–infected mice exhibited dose-dependent survival. The animals showed distention of the small intestine caused by peripheral neuritis because of infection of the myenteric plexus. Histopathologically, the strongly neurotropic Sofjin strain invaded the CNS of viremic mice via the autonomic nerves running from the plexus. The JaTH-160 strain of Japanese encephalitis virus was isolated from the lymph nodes during the preclinical phase of viral encephalitis. Therefore, this strain might infect the CNS via a hematogenous pathway, including through lymphoid tissues. The NY99-6922 strain of the West Nile virus caused clinical signs suggestive of intestinal, lymphoid, and/or neurologic involvement; the infected mice had prolonged viremia, suggesting that NY99-6922 may mainly use the hematogenous pathway; however, there was also histopathologic evidence of involvement of the autonomic nervous system pathway. In conclusion, the three neurotropic flaviviruses showed different pathogenesis, which were dependent upon overlapping but distinct pathways to CNS invasion after viremia.
Human Parechovirus 3 Meningitis and Fatal Leukoencephalopathy

Abstract Human parechovirus 3 (HPeV3) is a picornavirus associated with neurologic disease in neonates. Human parechovirus 3 infection of preterm and term infants is associated with seizures and destructive periventricular white matter lesions. Despite unremarkable cerebrospinal fluid (CSF), HPeV3 RNA can be amplified from CSF and nasopharyngeal and rectal swabs. We report pathologic findings in 2 autopsy cases of infants with active HPeV3 infection. Both children were born approximately 1 month premature and were neurologically intact but, after a few weeks, developed seizures and radiologic evidence of white matter lesions. Neuropathologic examination demonstrated classic severe periventricular leukomalacia in the absence of an immune response. Human parechovirus 3 sequences were identified in RNA extracted from CSF, sera, and tissues. Human parechovirus 3 in situ hybridization detection of infected cells was limited to meninges and associated blood vessels in addition to smooth muscle of pulmonary vessels. Ultrastructural evaluation of meninges demonstrated dense core structures compatible with picornavirus virions. These findings suggest that encephalopathic changes are secondary to infection of meninges and potential compromise of vascular perfusion. Thus, parechovirus infection of vascular smooth muscle may be a more general pathogenic process.
Evaluation of depression as a risk factor for treatment failure in chronic hepatitis C

The Major Depression Inventory (MDI) was used to estimate the value of routine medical interviews in diagnosing major depression among patients receiving peginterferon alfa‐2a and ribavirin therapy for chronic hepatitis C virus (HCV) infection (n = 325). According to criteria from the MDI and Diagnostic and Statistical Manual of Mental Disorders (DSM‐IV), 19 patients (6%) had major depression at baseline. An additional 114 (37%) developed depression while on HCV combination therapy, with baseline MDI score and female sex independently predicting the emergence of major depression during treatment in a multivariate analysis. Only 36 (32%) of the 114 patients developing major depression according to MDI/DSM‐IV criteria were correctly diagnosed during routine medical interviews. The emergence of major depression frequently led to premature discontinuation of peginterferon/ribavirin therapy, and an on‐treatment MDI score increment exceeding 30 points (i.e., a validated marker of idiopathic DSM‐IV major depression) was correlated with impaired outcome of HCV therapy (P = 0.02). This difference was even more pronounced among patients with an on‐treatment increase in MDI score greater than 35 points (P = 0.003). Conclusion: We conclude that (1) depressive symptoms among patients undergoing HCV therapy are commonly overlooked by routine clinical interviews, (2) the emergence of depression compromises the outcome of HCV therapy, and (3) the MDI scale may be useful in identifying patients at risk for treatment‐induced depression. (HEPATOLOGY 2010;)
Lack of Major Histocompatibility Complex Class I Upregulation and Restrictive Infection by JC Virus Hamper Detection of Neurons by T Lymphocytes in the Central Nervous System

Abstract The human polyomavirus JC (JCV) infects glial cells in immunosuppressed individuals, leading to progressive multifocal leukoencephalopathy. Polyomavirus JC can also infect neurons in patients with JCV granule cell neuronopathy and JCV encephalopathy. CD8-positive T cells play a crucial role in viral containment and outcome in progressive multifocal leukoencephalopathy, but whether CD8-positive T cells can also recognize JCV-infected neurons is unclear. We used immunohistochemistry to determine the prevalence of T cells in neuron-rich areas of archival brain samples from 77 patients with JCV CNS infections and 94 control subjects. Neurons predominantly sustained a restrictive infection with expression of JCV regulatory protein T antigen (T Ag), whereas glial cells were productively infected and expressed both T Ag and the capsid protein VP1. T cells were more prevalent near JCV-infected cells with intact nuclei expressing both T Ag and VP1 compared with those expressing either protein alone. CD8-positive T cells also colocalized more with JCV-infected glial cells than with JCV-infected neurons. Major histocompatibility complex class I expression was upregulated in JCV-infected areas but could only be detected in rare neurons interspersed with infected glial cells. These results suggest that isolated neurons harboring restrictive JCV infection do not upregulate major histocompatibility complex class I and thus may escape recognition by CD8-positive T cells.
Detection and Quantification of &bgr;-Amyloid, Pyroglutamyl A&bgr;, and Tau in Aged Canines

Abstract Canine cognitive dysfunction syndrome is an age-associated disorder that resembles many aspects of human Alzheimer disease. The characterization of canine cognitive dysfunction syndrome has been restricted to selected laboratory dogs and mongrels, thereby limiting our knowledge of potential breed-related and age-related differences. We examined the brains of 24 dogs from various breeds. The frontal cortex, hippocampus, and entorhinal cortex were investigated. Deposits of &bgr;-amyloid (A&bgr;) and tau were analyzed phenotypically and quantified stereologically. In all dogs aged 10 years or older, plaques containing pyroglutamyl A&bgr; and A&bgr;8–17 were detected. Within the ventral hippocampus, significantly more pyroglutamyl A&bgr; plaques were deposited in small and medium dogs than in large dogs. Hyperphosphorylated tau with formation of neurofibrillary tangles was observed in 3 animals aged 13 to 15 years. This study provides the first investigation of pyroglutamyl A&bgr; in comparison with total A&bgr; (as shown by A&bgr;8–17 immunoreactivity) in dogs of different breeds, sizes, and ages. Our results indicate that canine cognitive dysfunction syndrome is relatively common among aged canines, thereby emphasizing the relevance of such populations to translational Alzheimer disease research.
Cytosolic phospholipase A2α and peroxisome proliferator‐activated receptor γ signaling pathway counteracts transforming growth factor β–mediated inhibition of primary and transformed hepatocyte growth

Hepatocellular carcinoma often develops in the setting of abnormal hepatocyte growth associated with chronic hepatitis and liver cirrhosis. Transforming growth factor β (TGF‐β) is a multifunctional cytokine pivotal in the regulation of hepatic cell growth, differentiation, migration, extracellular matrix production, stem cell homeostasis, and hepatocarcinogenesis. However, the mechanisms by which TGF‐β influences hepatic cell functions remain incompletely defined. We report herein that TGF‐β regulates the growth of primary and transformed hepatocytes through concurrent activation of Smad and phosphorylation of cytosolic phospholipase A2α (cPLA2α), a rate‐limiting key enzyme that releases arachidonic acid for the production of bioactive eicosanoids. The interplays between TGF‐β and cPLA2α signaling pathways were examined in rat primary hepatocytes, human hepatocellular carcinoma cells, and hepatocytes isolated from newly developed cPLA2α transgenic mice. Conclusion: Our data show that cPLA2α activates peroxisome proliferator‐activated receptor γ (PPAR‐γ) and thus counteracts Smad2/3‐mediated inhibition of cell growth. Therefore, regulation of TGF‐β signaling by cPLA2α and PPAR‐γ may represent an important mechanism for control of hepatic cell growth and hepatocarcinogenesis. (HEPATOLOGY 2010;)
Glycosylation of fibroblast growth factor receptor 4 is a key regulator of fibroblast growth factor 19–mediated down‐regulation of cytochrome P450 7A1

De novo bile acid synthesis in the liver needs to be tightly regulated in order to maintain optimal bile flow and prevent cholestasis. In the liver, fibroblast growth factor 19 (FGF19) regulates bile acid synthesis by down‐regulating messenger RNA levels of cytochrome P450 7A1 (CYP7A1). FGF19 acts through fibroblast growth factor receptor 4 (FGFR4), and β‐Klotho has recently been recognized as a modulator of FGFR4 activity. However, its precise mechanism of action has not been thoroughly described. We show here that β‐Klotho is an endoplasmic reticulum–resident protein that affects the cellular abundance of different FGFR4 glycoforms. β‐Klotho binds and directs the core glycoform of FGFR4 to the proteasome, and it allows only a terminal glycoform to reach the plasma membrane. Only the terminal FGFR4 glycoform is phosphorylated upon FGF19 treatment of HepG2 cells, and this shows that only fully glycosylated FGFR4 is active in CYP7A1 down‐regulation. Conclusion: β‐Klotho enhances FGF19 signaling by binding the inactive, core‐glycosylated FGFR4 and preventing it from reaching the surface. These results indicate that β‐Klotho is an indirect regulator of FGFR4, whereas glycosylation is the master switch for FGF19 activity and regulation of bile acid synthesis. (HEPATOLOGY 2010)
Altered Oligodendrocyte Maturation and Myelin Maintenance: The Role of Antiretrovirals in HIV-Associated Neurocognitive Disorders

Abstract Despite effective viral suppression through combined antiretroviral therapy (cART), approximately half of HIV-positive individuals have HIV-associated neurocognitive disorders (HAND). Studies of antiretroviral-treated patients have revealed persistent white matter abnormalities including diffuse myelin pallor, diminished white matter tracts, and decreased myelin protein mRNAs. Loss of myelin can contribute to neurocognitive dysfunction because the myelin membrane generated by oligodendrocytes is essential for rapid signal transduction and axonal maintenance. We hypothesized that myelin changes in HAND are partly due to effects of antiretroviral drugs on oligodendrocyte survival and/or maturation. We showed that primary mouse oligodendrocyte precursor cell cultures treated with therapeutic concentrations of HIV protease inhibitors ritonavir or lopinavir displayed dose-dependent decreases in oligodendrocyte maturation; however, this effect was rapidly reversed after drug removal. Conversely, nucleoside reverse transcriptase inhibitor zidovudine had no effect. Furthermore, in vivo ritonavir administration to adult mice reduced frontal cortex myelin protein levels. Finally, prefrontal cortex tissue from HIV-positive individuals with HAND on cART showed a significant decrease in myelin basic protein compared with untreated HIV-positive individuals with HAND or HIV-negative controls. These findings demonstrate that antiretrovirals can impact myelin integrity and have implications for myelination in juvenile HIV patients and myelin maintenance in adults on lifelong therapy.
Distinctions Between Sluggish Cognitive Tempo, ADHD-IN, and Depression Symptom Dimensions in Spanish First-Grade Children

The objective of this study was to evaluate the validity of a new parent rating scale of Sluggish Cognitive Tempo (SCT). SCT was defined with 10 symptom domains—daydreams; attention fluctuates; absentminded; loses train of thought; easily confused; seems drowsy; thinking is slow; slow-moving; low initiative; and easily bored, needs stimulation—with each domain represented by multiple examples. Mothers’ and fathers’ ratings of SCT, ADHD-IN, ADHD-HI, oppositional defiant disorder (ODD), and depression symptoms along with ratings of academic and social impairment were obtained for a sample of 802 Spanish first-grade children (54% boys). SCT Symptom Domains 4 to 8 showed substantial loadings on the SCT factor (i.e., convergent validity) and substantially higher loadings on the SCT factor than the ADHD-IN factor (i.e., discriminant validity). This 5-domain measure of SCT showed good interrater and test–retest reliability for a 6-week interval. Higher scores on the 5-domain measure of SCT predicted higher levels of academic and social impairment even after controlling for ADHD-IN and depression. In contrast, higher levels of SCT were not uniquely related (or uniquely negatively related) to ADHD-HI and ODD, whereas ADHD-IN and depression were uniquely positively related to ADHD-HI and ODD. The new measure of SCT more clearly establishes that SCT, ADHD-IN, and depression represent independent symptom dimensions, thus providing a measurement tool to help determine if SCT and ADHD-IN dimensions have unique biological correlates and if SCT and ADHD meet the criteria for different disorders.
A pilot study of high‐dose short duration daptomycin for the treatment of patients with complicated skin and skin structure infections caused by gram‐positive bacteria

Background: Methicillin‐susceptible and ‐resistant (MRSA) Staphylococcus aureus are significant causes of complicated skin and skin structure infections (cSSSI). The bactericidal antibiotic daptomycin is approved for gram‐positive cSSSI at 4 mg/kg/day for 7–14 days, but the optimal dose level and duration of therapy have not been firmly established. This pilot study evaluated the efficacy and safety of daptomycin at 10 mg/kg every 24 h for 4 days [high‐dose short duration (HDSD) regimen] vs. standard of care therapy with vancomycin or semi‐synthetic penicillin for the treatment of cSSSI.
Epithelial‐to‐mesenchymal transition of murine liver tumor cells promotes invasion

Epithelial‐to‐mesenchymal transition (EMT) is predicted to play a critical role in metastatic disease in hepatocellular carcinoma. In this study, we used a novel murine model of EMT to elucidate a mechanism of tumor progression and metastasis. A total of 2 × 106 liver cells isolated from Ptenloxp/loxp/Alb‐Cre+ mice, expanded from a single CD133+CD45− cell clone, passage 0 (P0), were sequentially transplanted to obtain two passages of tumor cells, P1 and P2. Cells were analyzed for gene expression using microarray and real‐time polymerase chain reaction. Functional analysis included cell proliferation, migration, and invasion in vitro and orthotopic tumor metastasis assays in vivo. Although P0, P1, and P2 each formed tumors consistent with mixed liver epithelium, within the P2 cells, two distinct cell types were clearly visible: cells with epithelial morphology similar to P0 cells and cells with fibroblastoid morphology. These P2 mesenchymal cells demonstrated increased locomotion on wound healing; increased cell invasion on Matrigel basement membrane; increased EMT‐associated gene expression of Snail1, Zeb1, and Zeb2; and down‐regulated E‐cadherin. P2 mesenchymal cells demonstrated significantly faster tumor growth in vivo compared with P2 epithelial counterparts, with invasion of intestine, pancreas, spleen, and lymph nodes. Furthermore, P2 mesenchymal cells secreted high levels of hepatocyte growth factor (HGF), which we propose acts in a paracrine fashion to drive epithelial cells to undergo EMT. In addition, a second murine liver cancer stem cell line with methionine adenosyltransferase 1a deficiency acquired EMT after sequential transplantations, indicating that EMT was not restricted to Pten‐deleted tumors. Conclusion: EMT is associated with a high rate of liver tumor proliferation, invasion, and metastasis in vivo, which is driven by HGF secreted from mesenchymal tumor cells in a feed‐forward mechanism. (HEPATOLOGY 2010)
A Subpopulation of Rat Muscle Fibers Maintains an Assessable Excitation-Contraction Coupling Mechanism After Long-Standing Denervation Despite Lost Contractility

To define the time course and potential effects of electrical stimulation on permanently denervated muscle, we evaluated excitation-contraction coupling (ECC) of rat leg muscles during progression to long-term denervation by ultrastructural analysis, specific binding to dihydropyridine receptors, ryanodine receptor 1 (RYR-1), Ca2+ channels and extrusion Ca2+ pumps, gene transcription and translation of Ca2+-handling proteins, and in vitro mechanical properties andelectrophysiological analyses of sarcolemmal passive properties and L-type Ca2+ current (ICa) parameters. We found that in response to long-term denervation: 1) isolated muscle that is unable to twitch in vitro by electrical stimulation has very small myofibers but may show a slow caffeine contracture; 2) only roughly half of the muscle fibers with "voltage-dependent Ca2+ channel activity" are able to contract; 3) the ECC mechanisms are still present and, in part, functional; 4)ECC-related gene expression is upregulated; and 5) at any time point, there are muscle fibers that are more resistant than others to denervation atrophy and disorganization of the ECC apparatus. These results support the hypothesis that prolonged "resting" [Ca2+] may drive progression of muscle atrophy to degeneration and that electrical stimulation-induced [Ca2+] modulation may mimic the lostnerve influence, playing a key role in modifying the gene expression of denervated muscle. Hence, these data provide a potential molecular explanation for the muscle recovery that occurs in responseto rehabilitation strategies developed based on empirical clinical observations.
An Update on Evidence-Based Psychosocial Treatments for Eating Disorders in Children and Adolescents

Eating disorders are relatively common and serious disorders in adolescents. However, there are few controlled psychosocial intervention studies with this younger population. This review updates a previous Journal of Clinical Child and Adolescent Psychology review published in 2008. The recommendations in this review were developed after searching the literature including PubMed/Medline and employing the relevant medical subject headings. In addition, the bibliographies of book chapters and treatment guideline articles were reviewed; last, colleagues were asked for suggested additional source materials. Psychosocial treatments examined include family therapy, individual therapy, cognitive behavioral therapy, interpersonal psychotherapy, cognitive training, and dialectical behavior therapy. Using the most recent Journal of Clinical Child and Adolescent Psychology methodological review criteria, family treatment–behavior (FT-B) is the only well-established treatment for adolescents with anorexia nervosa. Family treatment–systemic and insight oriented individual psychotherapy are probably efficacious treatments for adolescents with anorexia nervosa. There are no well-established treatments for adolescents with bulimia nervosa, binge eating disorder, or avoidant restrictive food intake disorder. Possibly efficacious psychosocial treatments for adolescent bulimia nervosa include FT-B and supportive individual therapy. Internet-delivered cognitive behavioral therapy is a possibly efficacious treatment for binge eating disorder. Experimental treatments for adolescent eating disorders include enhanced cognitive behavioral therapy, dialectical behavioral therapy, cognitive training, and interpersonal psychotherapy. FT-B is the only well-established treatment for adolescent eating disorders. Additional research examining treatment for eating disorders in youth is warranted.
The Scientific Legacy of Little Hans and Little Albert: Future Directions for Research on Specific Phobias in Youth

We review issues associated with the phenomenology, etiology, assessment, and treatment of specific phobias in children and adolescents and provide suggestions for future research and clinical practice. In doing so, we highlight the early case studies of Little Hans and Little Albert and the advances that have been made following the publication of these seminal cases. In recent years, we have witnessed a deeper understanding of the etiology of specific phobias and developed a rich array of evidence-based assessments and treatments with which to address specific phobias in youth. Although much has been accomplished in this area of inquiry, we also note that much remains to be done before we can advance more fully our understanding, assessment, and treatment of specific phobias in youth. It will be important for future work to build more firmly on these developments and to better determine the moderators and mediators of change with our evidence-based treatments and to more vigorously pursue their dissemination in real-word settings.