A perturbed elliptic problem involving the p(x)-Kirchhoff type triharmonic operator

This paper examines the existence of weak solutions for a nonlinear boundary value problem of p(x)-Kirchhoff type involving the p(x)-Kirchhoff type triharmonic operator and perturbed external source terms. We establish our results by using a Fredholm-type result for a couple of nonlinear operators, in the framework of variable exponent Sobolev spaces

Therapeutic efficacy of ormeloxifene against hepatocellular carcinoma

Background: Hepatocellular carcinoma (HCC) is the most common primary liver cancer and leading cause of cancer related deaths worldwide. Severe toxicity and drug resistance to available chemotherapeutic agents display ineffective clinical response. Therefore, drug repurposing is gaining attention owing to their known biological activities and excellent safety profiles. Ormeloxifene (ORM), non-steroidal, selective estrogen receptor modulator (SERM), and exhibit diverse pharmacological activities. The aim of this study is to assess the therapeutic activity of ORM and to investigate the underlying molecular mechanism against hepatocellular carcinoma. Objective: To investigate the therapeutic activity of ormeloxifene in human hepatocellular carcinoma cells. Methodology: MTT and colony formation assays were performed in SK-Hep-1, Hep3B and C3A cells. In vitro functional assays were carried out for investigating effect of ORM on migration and invasion abilities of HCC cells using Boyden chamber and Matrigel assays respectively. Results: Functional analysis revealed that ORM treatment led to suppression of proliferation and colony formation in human hepatocellular carcinoma cells in dose and time-dependent manner compared to vehicle treated group. ORM treatment, as shown by wound healing and Matrigel invasion assay, respectively, suppresses the migration and invasion of human hepatocellular carcinoma cells. Further, experiments are underway to determine the effect of ORM on EMT markers using western blotting and qPCR techniques. Conclusion: Taken together, ORM exhibited potent anticancer effects against HCC and could be further explored as a novel therapeutic modality for the treatment of HCC

Resiliency in Adolescents at High Risk for Substance Abuse: Flexible Adaptation via Subthalamic Nucleus and Linkage to Drinking and Drug Use in Early Adulthood

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/92431/1/acer1741.pd

Comparison of conventional and dispersive solid phase extraction clean-up approaches for the simultaneous analysis of tetracyclines and sulfonamides in a variety of fresh vegetables

he extensive use of antibiotics in agriculture has led to the occurrence of residual drugs in different vegetables frequently consumed by humans. This could pose a potential threat to human health, not only because of the possible effects after ingestion but also because the transmission of antibiotic-resistant genes could occur. In this work, two accurate sample preparation procedures were developed and validated for the simultaneous analysis of sulfonamides (SAs) and tetracyclines (TCs) in four of the most widely consumed vegetables (lettuce, onion, tomato, and carrot) in Europe. The evaluated protocols were based on QuECHERS for extraction and subsequent clean-up by SPE (solid phase extraction) or dispersive SPE. Parameters affecting both extraction and clean-up were carefully evaluated and selected for accuracy of results and minimal matrix effect. Overall, apparent recoveries were above 70% for most of the target analytes with both analytical procedures, and adequate precision (RSD<30%) was obtained for all the matrices. The procedural limits of quantification (LOQPRO) values for SPE clean-up remained below 4.4 μg kg−1 for TCs in all vegetables except for chlortetracycline (CTC) in lettuce (11.3 μg kg−1) and 3.0 μg kg−1 for SAs, with the exception of sulfadiazine (SDZ) in onion (3.9 μg kg−1) and sulfathiazole (STZ) in carrot (5.0 μg kg−1). Lower LOQPRO values (0.1–3.7 μg kg−1) were obtained, in general, when dSPE clean-up was employed. Both methods were applied to twenty-five market vegetable samples from ecological and conventional agriculture and only sulfamethazine (SMZ) and sulfapyridine (SPD) were detected in lettuce at 1.2 μg kg−1 and 0.5 μg kg−1, respectively.Authors acknowledge financial support from the Elkartek project entitled “Emergencia y diseminación de resistencia a los antibióticos: vínculos entre salud humana, ganadería, alimentación y medioambiente (elkartek 20/88)”, the projects “Evaluación del riesgo de aparición y diseminación de resistencias a antibióticos en productos vegetales frescos y suelos de cultivo de la comunidad autónoma del País Vasco (PA21/05 and PA22/05)” inside the “Research projects targeted to agriculture 2020 program” of the Basque Government (Basque Country, Spain); and the Basque Government through the financial support as consolidated group of the Basque Research System (IT1446-22). I. Vergara-Luis and B. Gonzalez-Gaya are grateful to the University of the Basque Country (UPV/EHU) for their pre-doctoral and post-doctoral fellowships. I. Baciero thanks to the Basque Government for her pre-doctoral fellowship

The double burden of age and disease on cognition and quality of life in bipolar disorder

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/108337/1/gps4084.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/108337/2/gps4084-sup-0002-TableS1.pd

Differential prefrontal and subcortical circuitry engagement during encoding of semantically related words in patients with late‐life depression

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/109350/1/gps4165.pd

Brief Report: Excitatory and Inhibitory Brain Metabolites as Targets of Motor Cortex Transcranial Direct Current Stimulation Therapy and Predictors of Its Efficacy in Fibromyalgia

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/110535/1/art38945.pd

Reduced basal ganglia μ-opioid receptor availability in trigeminal neuropathic pain: A pilot study

Abstract Background Although neuroimaging techniques have provided insights into the function of brain regions involved in Trigeminal Neuropathic Pain (TNP) in humans, there is little understanding of the molecular mechanisms affected during the course of this disorder. Understanding these processes is crucial to determine the systems involved in the development and persistence of TNP. Findings In this study, we examined the regional μ-opioid receptor (μOR) availability in vivo (non-displaceable binding potential BPND) of TNP patients with positron emission tomography (PET) using the μOR selective radioligand [11C]carfentanil. Four TNP patients and eight gender and age-matched healthy controls were examined with PET. Patients with TNP showed reduced μOR BPND in the left nucleus accumbens (NAc), an area known to be involved in pain modulation and reward/aversive behaviors. In addition, the μOR BPND in the NAc was negatively correlated with the McGill sensory and total pain ratings in the TNP patients. Conclusions Our findings give preliminary evidence that the clinical pain in TNP patients can be related to alterations in the endogenous μ-opioid system, rather than only to the peripheral pathology. The decreased availability of μORs found in TNP patients, and its inverse relationship to clinical pain levels, provide insights into the central mechanisms related to this condition. The results also expand our understanding about the impact of chronic pain on the limbic system.http://deepblue.lib.umich.edu/bitstream/2027.42/112555/1/12990_2012_Article_533.pd