Publications by authors named "Gutkin A"

Signal detection theory (SDT) and two-high threshold models (2HT) are often used to analyze accuracy data in recognition memory paradigms. However, when reaction times (RTs) and/or confidence levels (CLs) are also measured, they usually are analyzed separately or not at all as dependent variables (DVs). We propose a new approach to include these variables based on multinomial processing tree models for discrete and continuous variables (MPT-DC) with the aim to compare fits of SDT and 2HT models.

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Telomerase (human telomerase reverse transcriptase (hTERT) is considered a hallmark of cancer, being active in cancer cells but repressed in human somatic cells. As such, it has the potential to serve as a valid cancer biomarker. Exosomal hTERT mRNA can be detected in the serum of patients with solid malignancies but not in healthy individuals.

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In the perception of Navon hierarchical stimuli (e.g., large letters made up of small letters), young adults identify large letters faster than small ones (known as 'global advantage') and identify more slowly small letters when they form a different (or incongruent) large letter (known as 'unidirectional global interference').

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Currently there are no specific therapies addressing the distinctive biology of human papillomavirus (HPV)-induced cancer approved for clinical use. Short interfering RNA (siRNA) has much potential for therapeutic manipulation of HPV E6/E7 oncoproteins. Lipid-based nanoparticles (LNPs) can be utilized for systemic transportation and delivery of siRNA at target site.

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Appraisal theories of emotion sustain that stimuli containing high biological relevance preferentially capture our attention, regardless of their valence. In this work, we study the priming effect of both cute and threatening pictures on global/local visual processing. Seventy-eight males and 168 females in different menstrual cycle phases performed the global/local Navon letter task immediately after observing cute (infants and baby animals), threatening (animals in aggressive poses) or neutral pictures.

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The global precedence effect (GPE), originally referring to processing hierarchical visual stimuli composed of letters, is characterised by both global advantage and global interference. We present herein a study of how this effect is modulated by the variables letter and sex. The Navon task, using the letters "H" and "S," was administered to 78 males and 168 females (69 follicular women, 52 luteal women, and 47 hormonal contraceptive users).

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Harnessing CRISPR-Cas9 technology for cancer therapeutics has been hampered by low editing efficiency in tumors and potential toxicity of existing delivery systems. Here, we describe a safe and efficient lipid nanoparticle (LNP) for the delivery of Cas9 mRNA and sgRNAs that use a novel amino-ionizable lipid. A single intracerebral injection of CRISPR-LNPs against (sgPLK1-cLNPs) into aggressive orthotopic glioblastoma enabled up to ~70% gene editing in vivo, which caused tumor cell apoptosis, inhibited tumor growth by 50%, and improved survival by 30%.

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CRISPR/Cas systems (clustered regularly interspaced short palindromic repeats) have emerged as powerful tools to manipulate the genome for both research and therapeutic purposes. However, the clinical use of this system is hindered by multiple challenges, such as the rate of off-target effects, editing efficiency, the efficacy of HDR, immunogenicity, as well as development of efficient and safe delivery vehicles that can carry these compounds. Tremendous efforts are being conducted to overcome these challenges, including the discovery and engineering of more precise and efficacious Cas nucleases.

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One of the major challenges in drug development is the delivery of therapeutics to the central nervous system (CNS). The blood-brain barrier (BBB), which modulates the passage of molecules from the CNS, presents a formidable obstacle that limits brain uptake of therapeutics and, therefore, impedes the treatment of multiple neurological pathologies. Targeted nanocarriers present an excellent opportunity for drug delivery into the brain leveraging on endogenous receptors to transport therapeutics across the BBB endothelium.

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Exosomes, nano-vesicles secreted from all types of cells in the human body, function as inter-cell communicators. This role of exosomes is fulfilled by their specific content, dependent on the origin of donor cells from which they are secreted. Exosomes contain a plethora of nucleic acids (DNA, RNA and micro RNA), proteins and lipids.

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Background: Telomerase (human telomerase reverse transcriptase (hTERT)) is considered a hallmark of cancer. The aim of our study was to evaluate the feasibility of the detection of hTERT transcripts in serum as a 'pan-cancer' diagnostic method.

Methods: Human telomerase reverse transcriptase mRNA levels were determined in serum and serum-derived exosomes from 133 patients with different malignancies and 45 healthy controls.

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Exosomes are small (30-100nm) vesicles secreted from all cell types serving as inter-cell communicators and affecting biological processes in "recipient" cells upon their uptake. The current study demonstrates for the first time that hTERT mRNA, the transcript of the enzyme telomerase, is shuttled from cancer cells via exosomes into telomerase negative fibroblasts, where it is translated into a fully active enzyme and transforms these cells into telomerase positive, thus creating a novel type of cells; non malignant cells with telomerase activity. All tested telomerase positive cells, including cancer cells and non malignant cells with overexpressed telomerase secreted exosomal hTERT mRNA in accordance with the endogenous levels of their hTERT mRNA and telomerase activity.

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Glioblastoma is a type of brain cancer arises from glial cells. Glioblastoma multiforme (GBM), a subtype of glioblastoma, is the most common and most aggressive primary brain tumor. Currently, GBM therapy includes surgery and post-operative high-doses of radiation and chemotherapy.

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Facemask ventilation has been associated with the development of postoperative nausea and vomiting, increasing the risk of tracheal aspiration; development of gastric distension that further impairs alveolar ventilation; perforation of gastric and duodenal ulcers; development of pneumothorax; extrabronchial air dissection; and development of cardiac dysrhythmias, including bradycardia from indirect vagal nerve stimulation. An unusual complication that occurred during prolonged facemask ventilation is presented: development of a pseudo-obstruction of the intrathoracic airway due to the presence of entrained esophageal air.

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Background: Solid organ transplant populations are at increased risk for serious clinical manifestations of West Nile virus (WNV) infection.

Objective: To monitor liver transplant recipients during the 2003 WNV season in Manitoba and to identify incidence, clinical presentation and serology.

Methods: Serial blood specimens were obtained from adult patients followed at the liver transplant outpatient clinic between May 2003 and October 2003.

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Background/aims: Occult hepatitis B virus (HBV) infection [HBV-DNA detection in hepatitis B surface antigen (HBsAg)-negative individuals] may cause acute and/or chronic liver disease. The objective of this study was to document the prevalence of occult HBV in an isolated, North American Inuit community.

Methods: Four hundred and eighty seven HBsAg negative sera (61% of the community population) were available for HBV-DNA testing by real time PCR.

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Counselling of patients with chronic hepatitis C infections is often limited to discussions regarding how the virus is transmitted and what can be done to decrease the risk of transmission to others. The purpose of the present study was to document the principal concerns of newly diagnosed and follow-up patients with chronic hepatitis C, and thereby enhance counselling strategies and content. Seventy newly diagnosed and 115 follow-up patients with chronic hepatitis C virus (HCV) infection were initially asked in an open-ended manner (volunteered concerns) and then to prioritize from a prepared list of seven potential concerns (prioritized concerns), to identify those concerns that were of utmost importance to them.

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Hepatitis B virus (HBV) infections continue to occur in adult hemodialysis units. A possible contributing factor is the presence of occult HBV (serum hepatitis B surface antigen [HBsAg] negative but HBV DNA positive). Two hundred forty-one adult hemodialysis patients were screened for occult HBV.

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Ofloxacin was used in the treatment of 24 patients with chronic bronchitis or pneumonia at the background of chronic bronchopulmonary and cardiovascular diseases. The drug was administered in accordance with 2 regimens: orally in a dose of 400 mg once a day (group I) and intravenously in a dose of 200 mg twice a day for 2 to 4 days followed by the drug oral use in the same dosage for 6 to 8 days (group II). The trial included comparison of the treatment efficacy by a complex of clinicobacteriological indices, estimation of the drug pharmacokinetics under the two regimens and prediction of the drug concentrations in blood with the mathematical models.

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Taped home relaxation training was evaluated in a single-case replication design across three patients suffering from tension headaches. Data from daily headache diaries indicated that headache frequency decreased substantially for two of the patients. For the third patient who reported almost continual headache pain, intensity was reduced by over 50%.

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Treatment integrity procedures, generally lacking in previous research, were employed for evaluation of relaxation training for tension headaches. Treatment integrity is the extent to which the therapist implements the relaxation procedure as described, and the degree to which the patients comply with the therapist's instructions. Objective compliance with the home practice of relaxation training was assessed using a microcomputer-based method which required the patient to squeeze a hand control when instructed to tense a muscle.

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The functional activity of erythrocytes and platelets was studied in 50 patients with various types of coronary heart disease. The patients' plasma exhibited higher ADP levels due to erythrocyte microhemolysis and higher platelet malonic dialdehyde and intracellular calcium, which led to enhanced platelet functional activity. Treating the patients with the calcium antagonist diltiazem was found to result in lower ADP and platelet calcium levels whereas the concentrations of malonic dialdehyde remained unchanged.

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