Aptamers as an approach to targeted cancer therapy.

Conventional cancer treatments can cause serious side effects because they are not specific to cancer cells and can damage healthy cells. Aptamers often are single-stranded oligonucleotides arranged in a unique architecture, allowing them to bind specifically to target sites. This feature makes them an ideal choice for targeted therapeutics. They are typically produced through the systematic evolution of ligands by exponential enrichment (SELEX) and undergo extensive pharmacological revision to modify their affinity, specificity, and therapeutic half-life. Aptamers can act as drugs themselves, directly inhibiting tumor cells. Alternatively, they can be used in targeted drug delivery systems to transport drugs directly to tumor cells, minimizing toxicity to healthy cells. In this review, we will discuss the latest and most advanced approaches to using aptamers for cancer treatment, particularly targeted therapy overcoming resistance to conventional therapies.

Idiopathic granulomatous mastitis: A case report and literature review.

Key Clinical Message: Idiopathic granulomatous mastitis (IGM) is a challenging chronic inflammatory disease in diagnosis with unknown etiology. Although the most appropriate treatment protocol has not yet been identified, prednisolone was used in our patient as an effective and practical choice in the treatment of IGM. Abstract: Idiopathic granulomatous mastitis (IGM) is a chronic inflammatory disease of the breast and mimics disorders such as breast cancer and breast abscess. Due to the uncommon of this disease, there is no definitive etiology, or treatment. A 38-year-old woman presented with a 3-week history of painful right retro-areolar mass. She had no history of breast trauma and a family history of breast cancer. She had a history of breastfeeding her second child for 12 months in the past year. Diagnostic tests and investigations led to the IGM diagnosis. Therefore, the patient was successfully treated with a course of corticosteroids, but after 2 months, during treatment, she developed Brucellosis. Despite the patient's Brucella infection and treatment with anti-Brucella drugs, prednisolone as an anti-inflammatory corticosteroid therapy was influential in the treatment of IGM.

Effect of the number and diversity of visual stimuli on the reproduction of short time intervals.

Presenting more items within a space makes the space look and feel bigger. Presenting more tones within a time interval makes the interval seem longer. Does presenting more visual items also make a time interval seem longer? Does it matter what these items are? A series of 2-4 images were presented sequentially on a screen. Participants had to press the spacebar to indicate either the interval between the first and the last item or the intervals between all items. The first and last items were red squares with onset asynchronies of 700, 900, or 1,100 ms. We found that the times between key presses were longer when additional items had different shapes and colors than when they were also red squares. With only red squares, the time may even decrease with the number of items. Whether one had to tap for all targets or only the first and the last hardly mattered.

Ability of polymicrobial probiotic and mono-strain probiotic to reduce functional abdominal pain in children: a randomized clinical trial.

BACKGROUND: Chronic abdominal pain is a common problem in childhood. PURPOSE: Due to the prevalence of functional abdominal pain (FAP) and the importance of probiotics, this study aimed to compare the ability of 2 probiotics to reduce and improve FAP in children. METHODS: This open-label randomized clinical trial included 116 children aged 5-15 years with FAPP who met the ROME-4 criteria and were referred to the gastrointestinal clinic of Amir-Kabir Hospital in Arak in 2020-2021. The children were randomly allocated to receive polymicrobial probiotic (PMP group) or mono-strain probiotic (MSP group) once daily for 4 weeks. The standard Wong-Baker Faces scale was used to assess symptom severity. RESULTS: Of the 116 subjects, 62 (53.5%) were boys; the mean participant age was 7.39 years (standard deviation, 3.4 years). A significant intergroup difference (P=0.003) was observed in pain severity; 10.34% of children in the PMP group had no pain, while all patients in the MSP group reported low-degree pain. There was no intergroup difference in mean pain score (P=0.466), but it decreased over time in both groups (P= 0.001). CONCLUSION: Although significantly more children were painless in the PMP versus MSP group, no significant intergroup difference in pain score was noted and symptom severity decreased in both groups. A future study with a placebo group is recommended to validate our findings.

Cognitive network reconstruction in individuals who use opioids compared to those who do not: Topological analysis of cognitive function through graph model and centrality measures.

Introduction: Cognitive dysfunction related to opioid use disorder (OUD) requires investigation of the interconnected network of cognitive domains through behavioral experiments and graph data modeling. Methods: We conducted n-back, selective and divided attention, and Wisconsin card sorting tests and reconstructed the interactive cognitive network of subscales or domains for individuals who use opioids and controls to identify the most central cognitive functions and their connections using graph model analysis. Each two subscales with significant correlations were connected by an edge that incorporated in formation of interactive networks. Each network was analyzed topologically based on the betweenness and closeness centrality measures. Results: Results from the network reconstructed for individuals who use opioids show that in the divided attention module, reaction time and number of commission errors were the most central subscales of cognitive function. Whereas in controls, the number of correct responses and commission errors were the most central cognitive measure. We found that the subscale measures of divided attention module are significantly correlated with those of other tests. These findings corroborate that persons who use opioids show impaired divided attention as higher reaction time and errors in performing tasks. Divided attention is the most central cognitive function in both OUD subjects and controls, although differences were observed between the two groups in various subscales. Discussion: Although equal proportions of males and females may be used in future studies, divided attention and its subscales may be the most promising target for cognitive therapies, treatments and rehabilitation as their improvement can enhance overall cognitive domain performance.

Age-standardized mortality rate and predictors of mortality among COVID-19 patients in Iran.

BACKGROUND: To have a thorough understanding of epidemic surveillance, it is essential to broaden our knowledge of death tolls worldwide. This study aimed to determine the age-standardized mortality rate (ASMR) and predictors of mortality among coronavirus disease 2019 (COVID-19) patients. MATERIALS AND METHODS: In this cross-sectional design, all COVID-19 patients with a positive polymerase chain reaction test in the population covered by Arak University of Medical Sciences (AUMS) were entered to the study. Data collection was conducted by phone interview. The study variables comprised age, sex, coronary heart diseases, diabetes, and some symptoms at admission. The adjusted odds ratio (OR) and 95% confidence intervals (CIs) were obtained by logistic regression. The direct method was applied to calculate ASMR (per 100,000) of COVID-19. The analysis was applied by STATA software 12.0. RESULTS: A total of 208 cases of COVID-19 (out of 3050 total infected cases) were dead and 2500 cases were recovered. The mean age of dead patients was 70 years. The COVID-19 fatality rate in the population equaled 6.8%; in those patients who were 70 years old or more, however, the case fatality rate was 16.4%. The ASMR of COVID-19 was 12.9 (CI 95%: 11.2, 14.8). The odds of COVID-19-related death in the age over 60 were 10.87 (CI 95%: 6.30, 18.75) times than lower 45 years old. Moreover, it was observed that COVID-19 significantly increased the odds of COVID-19-related death in diabetes patients (OR = 1.45, CI 95%: 1.02, 2.06, P = 0.036). CONCLUSION: The ASMR of COVID-19 was relatively higher in males than females. In general, the COVID-19 fatality rate was relatively high. We found that older age and diabetes can have impact on the death of COVID-19, but the headache was found to have a negative association with the COVID-19-related death.

The role of hypoxia in the tumor microenvironment and development of cancer stem cell: a novel approach to developing treatment.

Hypoxia is a common feature of solid tumors, and develops because of the rapid growth of the tumor that outstrips the oxygen supply, and impaired blood flow due to the formation of abnormal blood vessels supplying the tumor. It has been reported that tumor hypoxia can: activate angiogenesis, thereby enhancing invasiveness and risk of metastasis; increase survival of tumor, as well as suppress anti-tumor immunity and hamper the therapeutic response. Hypoxia mediates these effects by several potential mechanisms: altering gene expression, the activation of oncogenes, inactivation of suppressor genes, reducing genomic stability and clonal selection. We have reviewed the effects of hypoxia on tumor biology and the possible strategiesto manage the hypoxic tumor microenvironment (TME), highlighting the potential use of cancer stem cells in tumor treatment.

Alteration of TRIM33 Expression at Transcriptional and Translational Levels is Correlated with Autism Symptoms.

As a complex neurodevelopmental disorder, autism affects children in three major cognitive domains including social interactions, language learning and repetitive stereotyped behaviors. Abnormal regulation of cell proliferation in the brain during the embryonic period via the TGF-ß signaling pathway and TRIM33 gene that encodes a protein with a corepressor and regulatory role in this pathway has been considered as an etiology for autism. Here, we investigated the association of a variation of TRIM33 with autism symptoms at levels of mRNA and protein expression. We used Autism Diagnostic Interview-Revised (ADI-R) and Childhood Autism Rating Scale (CARS) as behavioral diagnostic tools. Normal and autistic children were genotyped for a TRIM33 polymorphism (rs11102807), and then expression was assessed at transcriptional and translational levels. Results demonstrated that the frequency of the homozygous A allele (AA genotype of rs11102807) was significantly higher in children with autism (P < 0.001), whereas carriers of the G allele were mostly among healthy individuals. Children homozygous for the rs11102807 A allele were associated with an increase in CARS and ADI-R scores, indicating a significant correlation with autism symptoms. TRIM33 gene expression at both mRNA (P < 0.01) and protein (P < 0.001) levels was significantly higher in controls compared to autistic children. A remarkable association between higher TRIM33 gene expression at the transcriptional level and lower scores for both CARS and ADI-R was observed in non-autistic children. It seems that rs11102807 modulates the function and expression of the TRIM33 gene, implying that the A allele may increase the risk of autism in children by reducing gene expression and altering the TGF-ß signaling pathway.

The relationship between hostility and anger with coronary heart disease in patients.

BACKGROUND: Cardiovascular disease accounts for 40% of the world's fatality and after accidents and traumas, is the second leading cause of death in Iran. Given the role of psychological characteristics such as hostility and anger in the development of certain behaviors and habits affecting heart problems, this study aimed to investigate the relationship between hostility and anger with coronary artery disease. METHODOLOGY: In this cross-sectional study, 320 patients referring to the hospital with coronary artery stenosis enrolled in the study and were available for angiography. Data collection tools included demographic and disease status questionnaires and aggression questionnaire. The data were analyzed by SPSS software version 16, and Spearman's correlation coefficient, Student's t-, and one-way analysis of variance tests was used for the statistical analysis. RESULTS: In this case, we have the following. Out of 302 cases, 183 were males and 119 were females. One hundred and ninety-seven patients with coronary artery disease and 105 patients with angiography had no coronary artery disease. CONCLUSION: People with coronary artery disease and healthy controls had no significant differences in demographic characteristics, history of illness, and education. Furthermore, there was no statistically significant relationship between hostility and anger with vasoconstriction. Since there is no relationship between hostility and anger with coronary artery disease, further studies are needed to investigate the presence of mediating variables to design appropriate and preventive interventions.

An integrative gene network-based approach to uncover the cellular and molecular infrastructures of schizophrenia.

AIMS: High phenotypic and endophenotypic heritability of schizophrenia indicates substantial involvement of genetic elements in the occurrence of this disorder. Multiplicity of hypotheses about the genetic basis of schizophrenia pathogenesis suggests that there is still no integrated image from cellular and molecular infrastructure of this disorder. MATERIALS AND METHODS: Here, we aimed to gain an integrated insight into the genetic basis of schizophrenia through gene set enrichment and network analysis to find the most important developmental stages/brain regions, chromosomal locations and metabolic pathways involved in the pathogenesis of schizophrenia. We investigated major mental disorders whose genetic bases are significantly overlapping with the schizophrenia gene set. KEY FINDINGS: Enrichment analyses uncovered 60 developmental stages/brain regions, 21 chromosomal hotspots and 16 pathways which are significantly associated with the found gene set. Our results demonstrated early mid-fetal/cortex as the most prominent developmental stage/brain region, chr16q22 as the most significant cytoband and the neuroactive ligand-receptor interaction as the most central pathway associated with schizophrenia. Further analyses revealed that autistic disorder has the most shared genes with schizophrenia. Moreover, mitogen-activated protein kinase-3 (MAPK3), calcium voltage-gated channel subunit alpha1 C (CACNA1C), solute carrier family 6 member 4 (SLC6A4) and 5-hydroxytryptamine receptor 2A (HTR2A) genes are the most central genes in the pathogenesis of schizophrenia. SIGNIFICANCE: In addition to summarizing what has been found on schizophrenia-associated genes in an integrative holistic framework, our results may help identify principle schizophrenia-associated cellular and molecular infrastructures, and provide support for further investigation on potential diagnostic and therapeutic biomarkers for schizophrenia.

A Novel Link between the Oxytocin Receptor Gene and Impulsivity.

Impulsivity includes hasty actions, social intrusiveness or premature decision-making. Neuropeptides like oxytocin alleviate haste and anxiety, and affect fear conditioning. However, no investigations have been done via gene-network based approach with cognitive and interventional genetic association studies to scrutinize the link between impulsive behavior and oxytocin. Here, interactive gene network and pathways associated with impulsivity were reconstructed, and serotonin transporter gene (SLC6A4) and serotoninergic synaptic transmission were identified as the most central gene and pathway related to impulsivity. Young healthy males received intranasal oxytocin or placebo, and impulsivity was evaluated via go/no-go test. Test performance scores then were analyzed based on commission and omission errors, response inhibition and reaction time. Blood DNA was extracted and a 761 bp intronic region in oxytocin receptor (OXTR) gene was amplified and sequenced using PCR-pyrosequencing. Employing Haploview, haplotypes and linkage disequilibrium (LD) pattern among all SNPs in the target sequence were determined based on D' and LOD values, and rs2254298 with the highest LD was indicated as the tag SNP. Oxytocin group and participants with GG genotype showed a significantly decreased commission error and increased inhibition. This means that oxytocin alleviated impulsive behavior, and subjects with GG genotype had lower rate of impulsivity than those with GA and AA genotypes. rs2254298 may modulate the function or expression of the OXTR gene, implying that G allele may increase the expression of OXTR gene compared to A allele. We suggest that intranasal oxytocin may notably moderate impulsive behavior and tendency to make hasty or premature decisions.

Nucleus basalis of Meynert modulates signal processing in rat layer 5 somatosensory cortex but leads to memory impairment and tactile discrimination deficits following lesion.

In rodents, exploring through continuous whisking is a process resulted from sensorimotor networking among different layers of somatosensory cortex (SC) such as layer 5 (L5) or barrel field, and regions like the nucleus basalis of Meynert (NBM). NBM is densely packed with cholinergic fibers and its dysfunction leads to diminished acetylcholine release within SC, tactile deficits and Alzheimer's disease (AD)-like memory impairment. Using extracellular single-unit recording, we investigated mechanisms underlying changes in response characteristics of L5b neurons to single or paired deflection of selected principle and adjacent whiskers (PW and AW), following NBM electrical stimulation in normal rats or ibotenic acid-induced NBM lesion leading to potential tactile deficiency and memory loss during passive avoidance learning (PAL) in AD-like neuropathology. Our results indicated that NBM electrical stimulation decreased ON and OFF response magnitude in nearly half of the units upon vibrissal deflection. The larger the response was evoked to whisker deflection before NBM stimulation, the smaller it gets after stimulation. Neuronal spontaneous activity was not changed with NBM stimulation or lesion. Leading to more sublinear response summation and decreased condition-test ratio, NBM lesion decreased ON response magnitude and facilitation, increased AW surround inhibition in paired whisker deflection, increased excitatory and decreased inhibitory receptive fields, weakened information processing during whisking, and resulted in AD-like declined PAL performance. These findings provide further understandings to develop translational approaches in precision therapeutics to target highly specific regions such as NBM or SC, and pathways like cholinergic system involved in tactile and memory deficits in AD.

Oxytocin moderates risky decision-making during the Iowa Gambling Task: A new insight based on the role of oxytocin receptor gene polymorphisms and interventional cognitive study.

The oxytocinergic system influences attentional bias towards emotional cues and feedback-based learning. Considering a tag single-nucleotide polymorphism (SNP) found through analysis of an intronic haplotype in the oxytocin receptor (OXTR) gene, we investigated the effect of oxytocin on risky decision-making via the Iowa Gambling Task (IGT). Young healthy males received intranasal oxytocin or placebo, and the IGT was performed where raw scores, net scores and total time were recorded, and ratio of advantageous to disadvantageous choices was calculated. Using PCR-pyrosequencing, a 761 bp target sequence in the OXTR gene was amplified and sequenced after the extraction of whole blood DNA. Employing Haploview, haplotypes and linkage disequilibrium (LD) pattern among all 14 SNPs in the intronic region were determined based on D' and LOD values, and rs2254295 with the highest LD was indicated as the tag SNP. GTT was shown to have the highest frequency among the found haplotypes. Oxytocin group and participants with the TT genotype demonstrated a significantly increased raw score, net score and advantageous choices, whereas the total time was not influenced remarkably. This means that oxytocin significantly reduced the risk taking in decision-making, and participants with the TT genotype had less premature or risky decisions than those with the CT and CC genotypes. rs2254295 may modulate the function or expression of the OXTR gene, implying that T allele may increase the expression of the OXTR gene compared to C allele. We suggest that oxytocin may remarkably moderate the risk attitude and its consequences during uncertain decision-making.

Chronic ghrelin administration restores hippocampal long-term potentiation and ameliorates memory impairment in rat model of Alzheimer's disease.

Alzheimer's disease (AD), as a common age-related dementia, is a progressive manifestation of cognitive decline following synaptic failure resulted majorly by senile plaques composed of deposits of amyloid beta (Aß). Ghrelin is a multifunctional peptide hormone with receptors present in various brain tissues including hippocampus and has been associated with neuroprotection, neuromodulation, and memory processing. Here, we investigated the neuroprotective and therapeutic effects of intracerebroventricular (icv) ghrelin infusion for 2 weeks on passive avoidance learning (PAL), memory retention, and synaptic plasticity in the hippocampal dentate gyrus (DG) and CA1 of both normal rats and Aß1-42-induced neurotoxicity in AD model. Male Wistar rats were evaluated for their passive memory performance using a shuttle box while some groups had already received Aß1-42 and/or chronic ghrelin. Using field potential recording, the induction of short- and long-term potentiation (STP and LTP) was studied in DG granule cells along with the LTP changes in CA1 pyramidal neurons through stimulation of the medial perforant path (mPP) and Schaffer collaterals (SCs), respectively. Our results demonstrated that chronic ghrelin treatment not only improved memory processing and retrieval in normal rats during the PAL task, but also promoted memory retention and alleviated memory loss by amelioration of Aß1-42-induced synaptic plasticity impairment in AD subjects through augmentation of field excitatory postsynaptic potential (fEPSP) slope that led to LTP restitution in both the mPP-DG and the CA3-CA1 synapses. Meanwhile, STP was not significantly changed, meaning that although ghrelin enhanced postsynaptic excitability in DG, it did not change presynaptic transmitter release significantly. This suggests the involvement of postsynaptic mechanisms in long-term ghrelin-enhanced memory. In conclusion, it can be inferred that chronic ghrelin administration has an auspicious therapeutic value for impaired cognitive performance and memory deficits in AD-like neuropathology.

Involvement of cannabinoid system in the nucleus accumbens on delay-based decision making in the rat.

The nucleus accumbens (NAc) plays a fundamental role in decision making and anticipation of reward. In addition, exogenous cannabinoids affect the behavior of humans and animals including disruption of short-term memory and cognitive impairments. Therefore, in this study, cannabinoid agonist and antagonist were administrated into the NAc to determine the effect of cannabinoid activation in the entire NAc on delay-based decision making. Rats were trained on a cost-benefit T-maze decision making task in which the animals were well-trained to choose between a small/immediate reward and a large/delay reward. After training, the animals were implanted with guide cannulae in the NAc. On test day, they received cannabinoid agonist (Win 55,212-2; 10, 50 and 100µM) and/or antagonist (AM251; 45µM) into the NAc. Percentage of high reward choice and latency of reward achievement were evaluated. Results showed that cannabinoid agonist administration caused a decrease in high reward choice such that rats selected small/immediate reward instead of large/delay reward. Moreover, in agonist-treated animals latency of reward achievement increased. Effects of cannabinoid activation on delay-based decision making with equivalent delays demonstrated that if the delay was equated on both arm goals, animals still had a preference for the high/delay reward, showing the results was not caused by an impairment of spatial preference or memory. These finding clarified that cannabinoid system activation in the entire NAc plays a critical role in the regulation of delay-based decision making.

MultIethNic Study of BrEast ARterial Calcium Gradation and CardioVAscular Disease: cohort recruitment and baseline characteristics.

PURPOSE: MultIethNic Study of BrEast ARterial Calcium Gradation and CardioVAscular Disease (MINERVA) was designed to answer the question of whether a novel continuous breast arterial calcification (BAC) mass score improves cardiovascular risk stratification among asymptomatic postmenopausal women. This article describes recruitment and baseline characteristics. METHODS: MINERVA is a multiethnic longitudinal cohort study. The phenotype data include BAC mass by densitometry applied to digital mammograms, sociodemographic factors, self-reported medical history, medications, parental history, reproductive history, smoking, alcohol consumption, physical activity, anthropometry, ankle-brachial index, blood pressure, laboratory panel, breast volumes, cognitive function, bioelectrical impedance, habitual diet, dietary supplements, sleep, psychosocial factors, and sun exposure. RESULTS: A total of 5145 women aged 60 to 79 years with available digital, uncompressed mammograms were recruited from the membership of Kaiser Permanente of Northern California between October 24, 2012 and February 13, 2015 and completed a baseline clinic visit or an abbreviated phone questionnaire. Of those, 4153 underwent phlebotomy and have blood biomarkers. Overall prevalence of BAC was 26%, and it varied by age and race. The mean (SD) BAC mass was 12 (23) mg and the range 0-342 mg. CONCLUSIONS: MINERVA is the first cohort with a continuous measure of BAC. The cohort is large, ethnically diverse, and deeply phenotyped in terms of socioeconomic, behavioral, and clinical factors, and blood biomarkers.

Comprehensive Assessment of Coronary Artery Disease by Using First-Pass Analysis Dynamic CT Perfusion: Validation in a Swine Model.

Purpose To retrospectively validate a first-pass analysis (FPA) technique that combines computed tomographic (CT) angiography and dynamic CT perfusion measurement into one low-dose examination. Materials and Methods The study was approved by the animal care committee. The FPA technique was retrospectively validated in six swine (mean weight, 37.3 kg ± 7.5 [standard deviation]) between April 2015 and October 2016. Four to five intermediate-severity stenoses were generated in the left anterior descending artery (LAD), and 20 contrast material-enhanced volume scans were acquired per stenosis. All volume scans were used for maximum slope model (MSM) perfusion measurement, but only two volume scans were used for FPA perfusion measurement. Perfusion measurements in the LAD, left circumflex artery (LCx), right coronary artery, and all three coronary arteries combined were compared with microsphere perfusion measurements by using regression, root-mean-square error, root-mean-square deviation, Lin concordance correlation, and diagnostic outcomes analysis. The CT dose index and size-specific dose estimate per two-volume FPA perfusion measurement were also determined. Results FPA and MSM perfusion measurements (PFPA and PMSM) in all three coronary arteries combined were related to reference standard microsphere perfusion measurements (PMICRO), as follows: PFPA_COMBINED = 1.02 PMICRO_COMBINED + 0.11 (r = 0.96) and PMSM_COMBINED = 0.28 PMICRO_COMBINED + 0.23 (r = 0.89). The CT dose index and size-specific dose estimate per two-volume FPA perfusion measurement were 10.8 and 17.8 mGy, respectively. Conclusion The FPA technique was retrospectively validated in a swine model and has the potential to be used for accurate, low-dose vessel-specific morphologic and physiologic assessment of coronary artery disease. © RSNA, 2017.

Genealogy Study of Three Generations of Patients with Bipolar Mood Disorder Type I.

INTRODUCTION: The purpose of this research is genealogy examination of three generation of bipolar mood disorder Type I patients. METHODS: Patients selected using Poisson sampling method from 100 patients with bipolar mood disorder Type I, referring to a psychiatric center of Amir Kabir Hospital of Arak, Iran. Examine issues such as physical ailments, psychological review of living and deceased family members of each patient, drawn family pedigree using pedigree chart, check the relationship of the different pattern of the autosomal dominant and recessive disease, sex-linked dominant and recessive and linked to Y chromosome have been performed on patients. Different methods used in this study are pedigree chart and young mania rating scale and SPSS and Pearson's correlation test for analyzing the data collected. RESULTS: Among the studied inheritance patterns, the most common inheritance pattern was autosomal recessive. There was a significant relationship between age, number of generation, and inheritance patterns with physical ailments in families of patients with bipolar mood disorder (P < 0.05), but there was no significant association with mental illness (P > 0.05). Furthermore, there was a significant relation between generation and skin, gastrointestinal, ovarian, lung, coronary heart disease, diabetes mellitus, hypertension, Cerebrovascular accident (CVA), hyperlipidemia, cardiomyopathy, hypothyroidism, and kidney disease in patients with bipolar affective disorder Type I (P < 0.05). CONCLUSION: The results showed that autosomal recessive was the most pattern of inheritance and there is a significant relationship between generation and some physical disorders in patients with bipolar mood disorder Type I.

Functional Assessment of Coronary Artery Disease Using Whole-Heart Dynamic Computed Tomographic Perfusion.

BACKGROUND: Computed tomographic (CT) angiography is an important tool for the evaluation of coronary artery disease but often correlates poorly with myocardial ischemia. Current dynamic CT perfusion techniques can assess ischemia but have limited accuracy and deliver high radiation dose. Therefore, an accurate, low-dose, dynamic CT perfusion technique is needed. METHODS AND RESULTS: A total of 20 contrast-enhanced CT volume scans were acquired in 5 swine (40±10 kg) to generate CT angiography and perfusion images. Varying degrees of stenosis were induced using a balloon catheter in the proximal left anterior descending coronary artery, and a pressure wire was used for reference fractional flow reserve (FFR) measurement. Perfusion measurements were made with only 2 volume scans using a new first-pass analysis (FPA) technique and with 20 volume scans using an existing maximum slope model (MSM) technique. Perfusion (P) and FFR measurements were related by PFPA=1.01 FFR-0.03 (R2=0.85) and PMSM=1.03 FFR-0.03 (R2=0.80) for FPA and MSM techniques, respectively. Additionally, the effective radiation doses were calculated to be 2.64 and 26.4 mSv for FPA and MSM techniques, respectively. CONCLUSIONS: A new FPA-based dynamic CT perfusion technique was validated in a swine animal model. The results indicate that the FPA technique can potentially be used for improved anatomical and functional assessment of coronary artery disease at a relatively low radiation dose.

Effects of dorsal hippocampal orexin-2 receptor antagonism on the acquisition, expression, and extinction of morphine-induced place preference in rats.

RATIONALE: Orexinergic system is involved in reward processing and drug addiction. OBJECTIVES: Here, we investigated the effect of intrahippocampal CA1 administration of orexin-2 receptor (OX2r) antagonist on the acquisition, expression, and extinction of morphine-induced place preference in rats. METHODS: Conditioned place preference (CPP) was induced by subcutaneous injection of morphine (5 mg/kg) during a 3-day conditioning phase. Three experimental plots were designed; TCS OX2 29 as a selective antagonist of orexin-2 receptors (OX2rs) was dissolved in DMSO, prepared in solutions with different concentrations (1, 3, 10, and 30 nM), and was bilaterally microinjected into the CA1 and some neighboring regions (0.5 µl/side). Conditioning scores and locomotor activities were recorded during the test. RESULTS: Results demonstrate that intra-CA1 administration of the OX2r antagonist attenuates the induction of morphine CPP during the acquisition and expression phases. Effect of TCS OX2 29 on reduction of morphine CPP was dose-dependent and was more pronounced during the acquisition than the expression. Furthermore, higher concentrations of TCS OX2 29 facilitated the extinction of morphine-induced CPP and reduced extinction latency period. Nevertheless, administration of TCS OX2 29 solutions did not have any influence on locomotor activity of all phases. CONCLUSIONS: Our findings suggest that OX2rs in the CA1 region of hippocampus are involved in the development of the acquisition and expression of morphine CPP. Moreover, blockade of OX2rs could facilitate extinction and may abrogate or extinguish the ability of drug-related cues, implying that the antagonist might be considered as a propitious therapeutic agent in suppressing drug-seeking behavior.