Apoptosis

Correction to: Autophagy inhibition with chloroquine reverts paclitaxel resistance and attenuates metastatic potential in human nonsmall lung adenocarcinoma A549 cells via ROS mediated modulation of β-catenin pathway The original version of this article unfortunately contained an error in acknowledgment text. The authors would like to include a statement: "Moumita Dasgupta is supported by Junior Research Fellowship from University Grant Commission, India." in acknowledgment section.

Potential role of anastasis in cancer initiation and progression

Inhibition of TNF-α-induced neuronal apoptosis by antidepressants acting through the lysophosphatidic acid receptor LPA 1 Abstract Tumor necrosis factor-α (TNF-α), a pro-inflammatory cytokine considered to be implicated in the pathogenesis of major depressive disorder, is a critical regulator of neuronal cell fate. In the present study we found that TNF-α-induced apoptosis of HT22 hippocampal cells, a neuroblast-like cell line, was markedly attenuated by the antidepressants mianserin, mirtazapine and amitriptyline. The anti-apoptotic effect of the antidepressants was blocked by either pharmacological inhibition or gene silencing of the lysophosphatidic acid receptor LPA1. Mianserin failed to affect TNF-α-induced caspase 8 activation, but inhibited the loss of mitochondrial membrane potential, the release of cytochrome c from mitochondria, procaspase 9 cleavage and downstream activation of caspase 3 in response to the cytokine. By acting through LPA1, mianserin also attenuated the enhanced pro-apoptotic response induced by the combination of TNF-α with other pro-inflammatory cytokines. TNF-α appeared to counterbalance its own pro-apoptotic response by activating NF-kB, ERK1/2 and JNK. Antidepressants had no significant effects on NF-kB activation, but potentiated the TAK-1-dependent phosphorylation of ERK1/2 and JNK elicited by the cytokine. This synergistic interaction was associated with enhanced JNK-mediated phosphorylation of Bcl-2 at Ser70 and increased ERK1/2-dependent mitochondrial accumulation of Mcl-1, two anti-apoptotic proteins that promote mitochondrial outer membrane stability. These results indicate that certain antidepressants, by activating LPA1 signalling, protect HT22 hippocampal cells from TNF-α-induced apoptosis through a mechanism involving, at least in part, the potentiation of the pro-survival pathways activated by the cytokine.

BDNF-mediated mitophagy alleviates high-glucose-induced brain microvascular endothelial cell injury Abstract Endothelial cell dysfunction and diabetic vascular complications are intrinsically linked. Although BDNF plays a protective role in cerebral microvascular complications caused by diabetes, the mechanisms of this activity are not fully clear. In this study, we investigated the role of BDNF in the hyperglycemic injury of BMECs and its associated intracellular signal transduction pathways. BMECs were treated with 33 mM glucose to imitate the endothelium under hyperglycemic conditions. The high-glucose treatment caused cell dysfunction, as evaluated by oxidative stress and cell apoptosis, which could be alleviated by BDNF. In addition, BDNF preserved mitochondrial function as assessed by mPTP opening, mitochondrial membrane potential, calcium content, and mitochondrial biogenesis markers. Western blot analysis of LC3-II, p62, and TOMM20 and the detection of mRFP-GFP-LC3 adenovirus for autophagy flux revealed that BDNF enhanced autophagy flux. Furthermore, BDNF activated mitophagy, which was confirmed by the observed colocalization of LC3-II with BNIP3 and from transmission electron microscopy observations. The HIF-1α/BNIP3 signaling pathway was associated with BDNF/TrkB-induced mitophagy. In addition, BDNF-induced mitophagy played a protective role against BMEC damage under hyperglycemia. Thus, the results of this study suggest that BDNF/TrkB/HIF-1α/BNIP3-mediated mitophagy protects BMECs from hyperglycemia.

Modulation of CD95-mediated signaling by post-translational modifications: towards understanding CD95 signaling networks Abstract CD95 is a member of the death receptor family and is well-known to promote apoptosis. However, accumulating evidence indicates that in some context CD95 has not only the potential to induce apoptosis but also can trigger non-apoptotic signal leading to cell survival, proliferation, cancer growth and metastasis. Despite extensive investigations focused on alterations in the expression level of CD95 and associated signal molecules, very few studies, however, have investigated the effects of post-translational modifications such as glycosylation, phosphorylation, palmitoylation, nitrosylation and glutathionylation on CD95 function. Post-translational modifications of CD95 in mammalian systems are likely to play a more prominent role than anticipated in CD95 induced cell death. In this review we will focus on the alterations in CD95-mediated signaling caused by post-translational modifications of CD95.

Autophagy inhibition with chloroquine reverts paclitaxel resistance and attenuates metastatic potential in human nonsmall lung adenocarcinoma A549 cells via ROS mediated modulation of β-catenin pathway Abstract Paclitaxel is one of the most commonly used drugs for the treatment of nonsmall cell lung cancer (NSCLC). However acquired resistance to paclitaxel, epithelial to mesenchymal transition and cancer stem cell formation are the major obstacles for successful chemotherapy with this drug. Some of the major reasons behind chemoresistance development include increased ability of the cancer cells to survive under stress conditions by autophagy, increased expression of drug efflux pumps, tubulin mutations etc. In this study we found that inhibition of autophagy with chloroquine prevented development of paclitaxel resistance in A549 cells with time and potentiated the effect of paclitaxel by increased accumulation of superoxide-producing damaged mitochondria, with elevated ROS generation, it also increased the apoptotic rate and sub G0/ G1 phase arrest with time in A549 cells treated with paclitaxel and attenuated the metastatic potential and cancer stem cell population of the paclitaxel-resistant cells by ROS mediated modulation of the Wnt/β-catenin signaling pathway, thereby increasing paclitaxel sensitivity. ROS here played a crucial role in modulating Akt activity when autophagy process was hindered by chloroquine, excessive ROS accumulation in the cell inhibited Akt activity. In addition, chloroquine pre-treatment followed by taxol (10 nM) treatment did not show significant toxicity towards non-carcinomas WI38 cells (lung fibroblast cells). Thus autophagy inhibition by CQ pre-treatment can be used as a fruitful strategy to combat the phenomenon of paclitaxel resistance development as well as metastasis in lung cancer.

Improved in vivo targeting of BCL-2 phenotypic conversion through hollow gold nanoshell delivery Abstract Although new cancer therapeutics are discovered at a rapid pace, lack of effective means of delivery and cancer chemoresistance thwart many of the promising therapeutics. We demonstrate a method that confronts both of these issues with the light-activated delivery of a Bcl-2 functional converting peptide, NuBCP-9, using hollow gold nanoshells. This approach has shown not only to increase the efficacy of the peptide 30-fold in vitro but also has shown to reduce paclitaxel resistant H460 lung xenograft tumor growth by 56.4%.

Proteasome inhibitors trigger mutations via activation of caspases and CAD, but mutagenesis provoked by the HDAC inhibitors vorinostat and romidepsin is caspase/CAD-independent Abstract Genotoxic anti-cancer therapies such as chemotherapy and radiotherapy can contribute to an increase in second malignancies in cancer survivors due to their oncogenic effects on non-cancerous cells. Inhibition of histone deacetylase (HDAC) proteins or the proteasome differ from chemotherapy in that they eliminate cancer cells by regulating gene expression or cellular protein equilibrium, respectively. As members of these drug classes have been approved for clinical use in recent times, we investigated whether these two drug classes exhibit similar mutagenic capabilities as chemotherapy. The HDAC inhibitors vorinostat/SAHA and romidepsin/FK288 were found to induce DNA damage, and mis-repair of this damage manifested into mutations in clonogenically viable surviving cells. DNA damage and mutations were also detected in cells treated with the proteasome inhibitor bortezomib. Exposure to both drug classes stimulated caspase activation consistent with apoptotic cell death. Inhibition of caspases protected cells from bortezomib-induced acute (but not clonogenic) death and mutagenesis, implying caspases were required for the mutagenic action of bortezomib. This was also observed for second generation proteasome inhibitors. Cells deficient in caspase-activated DNase (CAD) also failed to acquire DNA damage or mutations following treatment with bortezomib. Surprisingly, vorinostat and romidepsin maintained an equivalent level of killing and mutagenic ability regardless of caspase or CAD activity. Our findings indicate that both drug classes harbour mutagenic potential in vitro. If recapitulated in vivo, the mutagenicity of these agents may influence the treatment of cancer patients who are more susceptible to oncogenic mutations due to dysfunctional DNA repair pathways.

Fibroblasts from patients with idiopathic pulmonary fibrosis are resistant to cisplatin-induced cell death via enhanced CK2-dependent XRCC1 activity Abstract Idiopathic pulmonary fibrosis (IPF) is a deadly and progressive fibrotic lung disease, but the precise etiology remains elusive. IPF is characterized by the presence of apoptosis-resistant (myo)fibroblasts that relentlessly produce a collagen-rich extracellular matrix (ECM). Recent studies showed that an anti-cancer chemotherapy drug cisplatin is implicated in the development of pulmonary fibrosis, suggesting that the treatment of cancer patients with cisplatin may alter fibroblast viability. To address this possibility, we investigated the cisplatin-induced cell death mechanism in lung fibroblasts derived from IPF and non-IPF patients in response to a collagen matrix. IPF fibroblasts showed enhanced resistance to cisplatin-induced cell death compared to non-IPF fibroblasts in a time- and dose-dependent manner. Molecular study showed that the expression of γH2AX, PUMA and caspase-3/7 activity was abnormally reduced in IPF fibroblasts, suggesting that DNA damage-induced apoptosis caused by cisplatin was suppressed in IPF fibroblasts. Our study further revealed that DNA repair protein XRCC1 activity was aberrantly increased as a result of CK2 hyper-activation in cisplatin-treated IPF fibroblasts, and this alteration protected IPF fibroblasts from cisplatin-induced cell death. Our results showed that IPF fibroblasts residing in a collagen rich matrix are resistance to cisplatin-induced cell death due to the aberrantly high CK2/XRCC1-dependent DNA repair activity. This finding suggests that pulmonary fibrosis may develop and worsen due to the presence of apoptosis-resistant lung fibroblasts in cisplatin-treated cancer patients.

The neuroprotective action of 3,3′-diindolylmethane against ischemia involves an inhibition of apoptosis and autophagy that depends on HDAC and AhR/CYP1A1 but not ERα/CYP19A1 signaling Abstract There are no studies examining the effects of 3,3′-diindolylmethane (DIM) in neuronal cells subjected to ischemia. Little is also known about the roles of apoptosis and autophagy as well as AhR and ERα signaling and HDACs in DIM action. We demonstrated for the first time the strong neuroprotective capacity of DIM in mouse primary hippocampal cell cultures exposed to ischemia at early and later stages of neuronal development. The protective effects of DIM were mediated via inhibition of ischemia-induced apoptosis and autophagy that was accompanied by a decrease in AhR/CYP1A1 signaling and an increase in HDAC activity. DIM decreased the levels of pro-apoptotic factors, i.e., Fas, Caspase-3, and p38 mitogen-activated protein kinase (MAPK). DIM also reduced the protein levels of autophagy-related Beclin-1 (BECN1) and microtubule-associated proteins 1A/1B light chain (LC3), partially reversed the ischemia-induced decrease in Nucleoporin 62 (NUP62) and inhibited autophagosome formation. In addition, DIM completely reversed the ischemia-induced decrease in histone deacetylase (HDAC) activity in hippocampal neurons. Although DIM inhibited AhR/CYP1A1 signaling, it did not influence the protein expression levels of ERα and ERα-regulated CYP19A1 which are known to be controlled by AhR. This study demonstrated for the first time, that the neuroprotective action of 3,3′-diindolylmethane against ischemia involves an inhibition of apoptosis and autophagy and depends on AhR/CYP1A1 signaling and HDAC activity, thus creating the possibility of developing new therapeutic strategies that target neuronal degeneration at specific molecular levels.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Psychiatric Quarterly

Emotion Regulation and Desire Thinking as Predictors of Problematic Facebook Use Abstract Research evidence suggests that problematic Facebook use (PFU) affects large numbers of people worldwide. A variety of studies have investigated the relationship between PFU and psychological dysfunction, revealing that negative mood and cognitive self-regulation are common among problematic Facebook users. The aim of the present study was to examine the role of craving, emotion regulation and desire thinking in predicting PFU. An online survey was administered to 750 participants (Mage = 23.38 years; SDage = 5.72). Correlation analyses indicated that all predictor variables were positively associated with PFU. Path analysis showed that imaginal prefiguration was associated with craving, which, in turn, was associated with verbal prefiguration that was directly linked to PFU, beyond the direct effect of emotion regulation. These findings provide further support for the importance of desire thinking in predicting problematic behaviours. Desire thinking and emotion regulation should be considered in the modification of problematic Facebook use.

Intervention Effects of Motivation Interviewing Chinese Modified on the Mental Health of College Students with Exercise Dependence Abstract Exercise dependence is a psychological problem that cannot be ignored and is positively related to anxiety and depression of college students. However, only a few effective intervention methods are available to deal with exercise dependence. This study aims to investigate the intervention effects of motivation interviewing Chinese modified on the mental health of college students with exercise dependence. Thirty college students with exercise dependence were selected from Hunan University of Science and Technology in Hunan province of China to participate in the experiment. The participants were divided equally into the intervention and control groups. A three-week motivation interviewing Chinese modified session was conducted in the intervention group, whereas no intervention was carried out in the control group. This strategy allowed for the vertical and the horizontal comparison of the intervention objects' situation before and after the experiment. The State-Trait Anxiety Inventory and other Scales were used to evaluate the effects of the intervention and explore the intervention effects of motivation interviewing Chinese modified on the mental health of college students with exercise dependence. After three weeks of motivation interviewing Chinese modified, differences in state anxiety, depression, self-satisfaction, negative emotion, energy, and positive emotion in the intervention and control groups before and after the intervention appear to be statistically significant (P < 0.05). Motivation interviewing Chinese modified can improve the mental health level of college students with exercise dependence. Hence, motivation interviewing Chinese modified is good for the treatment of addiction behaviors and provides a reliable intervention method for exercise dependence.

Media Use Is Linked to Lower Psychological Well-Being: Evidence from Three Datasets Abstract Adolescents spend a substantial and increasing amount of time using digital media (smartphones, computers, social media, gaming, Internet), but existing studies do not agree on whether time spent on digital media is associated with lower psychological well-being (including happiness, general well-being, and indicators of low well-being such as depression, suicidal ideation, and suicide attempts). Across three large surveys of adolescents in two countries (n = 221,096), light users (<1 h a day) of digital media reported substantially higher psychological well-being than heavy users (5+ hours a day). Datasets initially presented as supporting opposite conclusions produced similar effect sizes when analyzed using the same strategy. Heavy users (vs. light) of digital media were 48% to 171% more likely to be unhappy, to be in low in well-being, or to have suicide risk factors such as depression, suicidal ideation, or past suicide attempts. Heavy users (vs. light) were twice as likely to report having attempted suicide. Light users (rather than non- or moderate users) were highest in well-being, and for most digital media use the largest drop in well-being occurred between moderate use and heavy use. The limitations of using percent variance explained as a gauge of practical impact are discussed.

PG-13 Rated Movie Violence and Societal Violence: is there a Link? Abstract Recent scholarship has suggested that the frequency of violence in PG-13 rated movies has increased in recent years. Although some scholars have expressed concern that such an increase may have public health implications, this has remained untested. In the current article, trends in PG-13 movie violence are tested against trends in violence in society, including both homicides and youth violence. Raw correlations suggest that PG-13 rated movie violence is inversely related to actual violence in society. However, controlling for autocorrelations suggests that the best interpretation is that PG-13 rated movie violence is unrelated to violence in society. Caution is advised for scholars to avoid implying that PG-13 rated movie violence may have a causal effect on crime in society.

Hospitalization Patterns over 30 Years Across a Statewide System of Public Mental Health Hospitals: Readmission Predictors, Optimal Follow-Up Period, Readmission Clusters and Individuals with Statistically Significant High Healthcare Utilization Abstract Four related hospital utilization questions (optimal follow-up period, predictors of readmission, definition of individuals with statistically significant high healthcare utilization, and patterns of readmissions) were examined using data for 491,094 hospital discharges for 250,091 patients across a statewide public mental health hospital system for 30 years (1987 to 2016). Using survival analysis, the first quartile of the survival time, the time when 25% of the entire population of discharges had a readmission was 229 days. Using observed readmissions, rather than the population as in survival analysis, revealed that 50% of all observed readmissions occurred by 222 days. Both suggest that using a one year observation period for determining high utilization may be reasonable. Major predictors of readmission were diagnoses of schizophrenia (OR = 2.11) or bipolar disorder (OR = 1.57) as well as total number of previous discharges (OR = 1.23). Statistically significant z scores (p < .01) were used to determine annual (3 or more discharges) and lifetime (7 or more discharges) criteria for individuals with statistically significant high healthcare utilization that were somewhat lower than in previous research. Cluster analysis of all readmissions revealed four relatively distinct clusters of patients: short stay-quick readmission, extremely long stay, long time in community between readmissions and frequent readmissions. While no cluster corresponded exactly with the annual statistically significant high healthcare utilization criteria, the frequent readmission cluster was somewhat similar to the lifetime statistically significant high healthcare utilization criteria with 46% of this cluster's patients having 7 or more discharges.

Working Nursing Students Willing to Seek Psychological Services Abstract Work-related psychological stress may result in reduced coping abilities. Working nursing students can develop work-related psychological stress. This study's purpose was to describe first-year working rural nursing students with work-related psychological stress and their perception of stigma to psychological services and perceived willingness and openness to seek such services. Results showed over 55% of students reported work-related stress and a willingness to seek psychological services. Students in a licensed practical nursing program showed less stigma to seeking psychological services (F (2, 23) = 10.09, p = 0.001) as compared to higher degree seeking students in associate and bachelor nursing programs. Stigma appeared not to be a factor in rural nursing students seeking psychological services. In conclusion, working nursing students are willing to seek psychological services regardless of stigma.

Enhancing Completion of Cognitive Processing Therapy for Posttraumatic Stress Disorder with Quetiapine in Veterans with Mild Traumatic Brain Injury: a Case Series Abstract To evaluate the outcomes of the antiarousal medications valproate, risperidone, and quetiapine on completion of treatment of cognitive processing therapy (CPT) for PTSD. A case series of fifty treatment-seeking adult (≥18 years) veterans with mild traumatic brain injury and combat-related PTSD who had unsuccessful trials of 2 or more first-line agents and previously declined treatment with trauma-focused therapy, seen at the psychiatric outpatient services of the local Polytrauma Rehabilitation Center from January 1, 2014, through December 31, 2017. Patients were prescribed valproate (n = 8), risperidone (n = 17), or quetiapine (n = 25) and were referred for individual weekly treatment with CPT. Outcome measurements of interest were measures of engagement and completion rate of CPT, PTSD Checklist total score (range, 0–80; higher scores indicate greater PTSD severity) and arousal subscale score (range, 0–24; higher scores indicate greater arousal severity), and clinical observations of sleep variables. Of the 50 patients included in the study, 48 (96%) were men; mean (SD) age was 36 (8) years. Eighteen (86%) patients initially receiving quetiapine and none taking valproate or risperidone became adequately engaged in and completed CPT. Among patients who completed CPT, the mean decrease in the PTSD Checklist score was 25 [95% CI, 30 to 20] and 9 (50%) patients no longer met criteria for PTSD. These preliminary findings support quetiapine as an adjunctive medication to facilitate CPT. A pragmatic trial is needed to evaluate the efficacy, safety, and feasibility of quetiapine to improve engagement in and completion rate of CPT.

Gender Differentiation of Indirect Self-Destructiveness in Drug Addicted Individuals (Indirect Self-Destructiveness in Addicted Women and Men) Abstract The use of psychoactive substances is considered to be a typical self-destructive behaviour with addiction itself regarded as one of the self-destructiveness forms. The aim of this work was to explore the gender differentiation of the indirect self-destructiveness syndrome (and its particular categories) in drug addicted individuals treated in drug addiction treatment centres. 172 drug addicted individuals (116 men and 56 women, M age = 23,5), ranged from 19 to 28 years, was recruited. In order to examine indirect self-destructiveness and its manifestations, the Polish version of the "Chronic Self-Destructiveness Scale" by Kelley (CS-DS) was administered. The statistical processing of scores used the Mann-Whitney U significance test. Women treated for drug addiction achieved significantly higher scores on indirect self-destructiveness: general score (p = 0.001), subscales of Transgression and Risk (p = 0.001), Personal and Social Neglects (p = 0.02), and Lack of Planfulness (p < 0.001). They scored lower on Poor Health Maintenance (p < 0.002) and Helplessness (p < 0.001). There is a need for specific, gender-adjusted manners of intervention and treatment in addicted women. Optimistically, after an addiction treatment, women cope and feel better psychologically and socially. They also care more about their health.

Folie du système? Preventing Violence Against Nurses in In-patient Psychiatry Abstract Violence against psychiatric nurses is a difficult reality of work on in-patient psychiatry units. Health care providers and managers, nursing unions, and workplace protection agencies are looking for solutions to improve safety and quality of care. We are suggesting that simultaneous to this solution-seeking, there is also a need to critically reflect on the nature of violence itself within in-patient psychiatric settings. In this article we consider the gendered dynamics of power and violence within the in-patient psychiatric setting. The nursing profession is over 90% female. Given that violence in society often has a 'gendered' nature, and in light of a report from the Ontario Council of Hospital Unions which likened violence against nurses to domestic violence, we have put forth a view of the acute in-patient psychiatric milieu that considers gender and power in its analysis of violence against nurses. Intended to encourage enquiry into our pre-suppositions as health care providers, we use Foucauldian and feminist theories to up-end our notions of "anti-violence technologies", and to consider the unique and risky position that psychiatric nurses occupy as carers, care providers, and "anti-violence officers". We conclude by posing ethical questions which may be of interest for professional development, care planning, team building, and clinical ethics and education.

Insight and Symptom Severity in an Inpatient Psychiatric Sample Abstract Individuals with a severe mental illness, particularly a psychotic disorder, often lack insight into having a mental illness. This study sought to examine the differences in insight and symptom severity between individuals with psychotic, bipolar, and depressive disorders in an inpatient psychiatric sample. 199 participants were interviewed and medical records were consulted. Results show that participants with a psychotic disorder had significantly less insight into their illness, more debilitating symptoms, and reported less depression symptoms after controlling for education, race, marital status, homelessness, age, gender, and history of incarceration. Insight was shown to be a mediator between having a psychotic disorder and symptom severity. Subjective quality of life did not differ by diagnosis. Substance use was not associated with insight or overall symptom severity, while homelessness was associated with having a psychotic disorder and more severe symptoms. Fostering insight during an inpatient stay may be an important part of reducing symptom severity and preventing patient relapse. However, greater insight may increase depression and suicidality, indicating a need for mood management and safety planning along with psychoeducation of symptoms.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Research in Pharmaceutical Sciences

Siamese neem flower extract suppresses cholesterol absorption by interfering NPC1L1 and micellar property in vitro and in intestinal Caco-2 cells Acharaporn Duangjai, Atcharaporn Ontawong, Chutima Srimaroeng Research in Pharmaceutical Sciences 2019 14(3):190-200 Siamese neem (Azadirachta indica A. Juss var. siamensis Valeton) (A. indica) leaf extract, a traditional ayurvedic medicine, has been reported to exhibit antipyretic, antibacterial, antidyslipidemic, and antihyperglycemia effects. This study investigated the mechanism of hypocholesterolemic effect of methanolic extract of Siamese neem flowers in in vitro studies and in Caco-2 cells. Pancreatic cholesterol esterase and 3-hydroxy 3-methylglutaryl-CoA (HMG-CoA) reductase activities were assessed. Cholesterol micelle formation was prepared for in vitro cholesterol physicochemical property analyses, micelle size and solubility, and transport of cholesterol into the Caco-2 cells. The expression of niemann-pick C1 like 1 (NPC1L1), and its major regulator, peroxisome proliferator-activated receptor δ (PPARδ), were determined by western blot and real time polymerase chain reaction, respectively. A. indica flower extract inhibited pancreatic cholesterol esterase activity and increased cholesterol micelles size. Uptake of cholesterol into Caco-2 cells was inhibited by A. indica flower extract in a dose-dependent manner. In addition, A. indica extract inhibited HMG-CoA reductase activity, resulting in low level of intracellular cholesterol accumulation, together with increased cytosolic NPC1L1 protein expression and decreased PPARδ gene expression. In conclusion, A. indica flower extract has cholesterol-lowering effects by inhibiting intestinal cholesterol absorption, interfering micellar cholesterol formation, and attenuating cholesterol synthesis. As such, A. indica flower extract has potential for developing into nutraceutical product for prevention of hypocholesterolemia.

Protective effects of melatonin solid lipid nanoparticles on testis histology after testicular trauma in rats Mehri Mirhoseini, Zahra Rezanejad Gatabi, Majid Saeedi, Katayoun Morteza-Semnani, Fereshteh Talebpour Amiri, Hamid Reza Kelidari, Abbas Ali Karimpour Malekshah Research in Pharmaceutical Sciences 2019 14(3):201-208 Testicular traumatic injuries occur frequently, which can result in an alteration in spermatogenesis. These injuries can also cause oxidative stress and male infertility. Antioxidant efficiency of melatonin (MLT), known as a potent antioxidant, will be improved if used in a form of solid lipid nanoparticles (MLT-SLN). The aim of the current study is to evaluate the effect of MLT-loaded SLN on traumatic testis in rats. In this study 32 adult male Wistar rats were divided into 4 groups. Group 1 (sham group), right testicle was drawn out from the scrotum and returned without manipulation. Group 2, right testicle was dropped by 25 g sinker for 4 times. Group 3, animals were received a single dose (25 mg/kg) of MLT intraperitoneally after trauma. Group 4, animals were received a single dose of MLT-SLN intraperitoneally after trauma. Under anaesthesia, rats were sacrificed, and their testicles were removed three days after the surgery. After tissue processing, the sample sections were H&E stained. MLT and MLT-SLN could partially repair spermatogenesis by Johnson’s criteria but the repairs were significant only in MLT-SLN group (P = 0.02). Trauma decreased seminiferous tubule diameter and its epithelium height. MLT could restore epithelium height (P ≤ 0.05) but its NPs improved both epithelium diameter (P ≤ 0.05) and thickness (P ≤ 0.001). The Malondialdehyde increased significantly in trauma group (P = 0.002), but decreased in MLT and NPs groups compared to trauma group (P = 0.098 and P = 0.002 respectively). This decrease was significant only in NPs group. Testicular trauma disturbed spermatogenesis, morphometric, and oxidative parameters. MLT and specially MLT-SLN improved traumatic damages.

Differentiation of adult human mesenchymal stem cells into dopaminergic neurons Marjan Khademizadeh, Manoochehr Messripour, Nazem Ghasemi, Fariborz Momen beik, Ahmad Movahedian Attar Research in Pharmaceutical Sciences 2019 14(3):209-215 The striatal dopamine (DA) deficiency is known as the main cause of the clinical picture of Parkinson’s disease (PD). The disease is a progressive degeneration of dopaminergic neurons in the striatum. The treatment of PD is based on compensation for the brain’s supply of DA lost by drug therapy, deep brain stimulation, surgery, gene and cell therapies. Clinical studies have focused on the utility of stem cell-based therapies in PD. Embryonic and mesenchymal stem cells (MSCs) are widely used. Recently, human adipose derived stem cells (hADSCs) have been considered as a suitable source of tissue for this purpose. In this project, hADSCs differentiated into dopaminergic neurons and the specificity of the cell preparations was examined. Human adipose tissues were collected from healthy volunteers undergoing liposuction and hADSCs were isolated by collagenase-based enzymatic method. Flow cytometry was performed using the surface cluster of differentiation (CD) markers to confirm the cell typical properties. Then hADSCs were differentiated to dopaminergic neurons in neurobasal medium in the presence of differentiation factors and confirmed by immunocytochemistry via neuronal and dopaminergic markers. The isolated hADSCs were cultured and identified by the expression of MSCs surface markers including CD90, and CD44. These cells did not express hematopoietic surface markers such as CD45 and CD14. Differentiated cells express neuronal marker NeuN and dopaminergic marker tyrosine hydroxylase (TH). It is concluded that hADSCs can be easily taken from the patient’s own body and differentiated into dopaminergic cells having a lower risk of transplant rejection.

β-lactoglobulin-irinotecan inclusion complex as a new targeted nanocarrier for colorectal cancer cells Nooshin Bijari, Sirous Ghobadi, Katayoun Derakhshandeh Research in Pharmaceutical Sciences 2019 14(3):216-227 Beta-lactoglobulin (β-LG) is a lipocalin family member whose general function appears to be solubilizing and transport of hydrophobic molecules. Some properties such as avalability, ease of purification, and peculiar resistance to acidic environments can make β-LG as a carrier for hydrophobic and acid labile drugs for oral administration. In this protein vehicle, drug could be protected in acidic environment of stomach and then released within the basic small intestine. In this study, the potential of β-LG as a nanocarrier for oral delivery of a potent agent in colorectal cancer treatment, irinotecan, was evaluated. The nanoparticle was prepared by the physical inclusion complex method. Size, drug loading, encapsulation efficiency, and in vitro drug release at various pH values were investigated. The optimum formulation showed a narrow size distribution with an average diameter of 139.86 ± 13.75 nm and drug loading about 84.33 ± 5.03%. Based on the results obtained from docking simulation of irinotecan-complex, there are two distinct binding sites in this nanocarrier. Cytotoxicity of this nanocarrier on the HT-29 cancer cell line and AGS was measured by MTT assay. The cytotoxicity experiment showed that the drug-loaded nanocarrier was more effective than free drug. The higher release percent of drug from the β-LG complex at pH 7.4 compared to pH 1.2 indicated that the proposed nanocarrier could be introduced as a suitable nanovehicle for labile drugs in acidic medium targeted for colorectal segment.

Anti-inflammatory effects of alosetron mediated through 5-HT3 receptors on experimental colitis Azadeh Motavallian, Mohsen Minaiyan, Mohammad Rabbani, Parvin Mahzouni, Sasan Andalib Research in Pharmaceutical Sciences 2019 14(3):228-236 Development of new medicine with fewer deleterious effects and more efficacies for treatment of inflammatory bowel disease is needed. 5-Hydroxytryptamine 3 receptor (5-HT3R) antagonists have exhibited analgesic and anti-inflammatory features in vitro and in vivo. The present study was designed to evaluate the anti-inflammatory effect of alosetron, a 5-HT3R antagonist, on trinitrobenzenesulfonic acid (TNBS)-induced ulcerative colitis in rats. Two h subsequent to induce colitis (intracolonic instillation of TNBS, 50 mg/kg) in male Wistar rats, alosetron (1 mg/kg), dexamethasone (1 mg/kg), meta-chlorophenylbiguanide (mCPBG, a 5-HT3R agonist, 5 mg/kg), or alosetron + mCPBG were administrated intraperitoneally for 6 days. Animals were thereafter sacrificed and the efficacy of drugs was evaluated macroscopically, histologically, and biochemically (myeloperoxidase, tumor necrosis factor-alpha, interleukin-6, and interleukin-1 beta) on distal colon samples. Treatment with alosetron and dexamethasone improved macroscopic and microscopic colonic damages significantly and decreased myeloperoxidase activity and colonic levels of inflammatory cytokines. The profitable effects of alosetron were antagonized by concurrent administration of mCPBG. Our data provided evidence that the protective effects of alosetron on TNBS-induced colitis can be mediated by 5- HT3R.

Effects of thyroxine on adhesion molecules and proinflammatory cytokines secretion on human umbilical vein endothelial cells Attabak Milani, Mohammad Hassan Khadem-Ansari, Yousef Rasmi Research in Pharmaceutical Sciences 2019 14(3):237-246 Thyroid dysfunction is associated with elevated cardiovascular risk factors and atherosclerosis. It could be suggested that, hyperthyroidism is related to a higher prevalence of arterial abnormalities. Therefore, evaluating the endothelial dysfunction (ED) related biomarkers seem to be an important issue. It is not clear whether endothelial cells are biologically responsive to thyroid hormones (THs) or how THs induces the production of endothelial cells (EC)-derived proinflammatory mediators. Hence, in this study the effects of thyroxine (T4) on ED and inflammatory related mediators were evaluated. Human umbilical vein endothelial cells was used as endothelial cell model which was treated with concentrations of 50, 100, 200 nmol/L of T4 in various exposure times. In the following, gene and protein expression levels of EC-related markers including intercellular adhesion molecule-1 (ICAM-1), vascular endothelial growth factor (VEGF), and E-selectin were determined using real time polymerase chain reaction (RT-PCR) and western blotting methods. Also, interleukin-6 (IL-6) and tumor necrosis factor (TNF-α) protein levels as proinflammatory cytokines were determined by enzyme linked immunosorbent assay (ELISA) method. Gene and protein expression analysis revealed that T4 treatments up regulated the levels of VEGF, ICAM-1, and E-selectin as ED markers. In addition, T4-treated cells had higher significant levels of IL-6 and TNF-α versus untreated cells in different incubation times. This study proposed the atherosclerotic effects of thyroid hormone. Based on our findings, T4 had strong effects on the gene and protein expression levels of pro-inflammatory, angiogenesis, and ED major mediators associated with atherosclerosis development.

Synthesis and cytotoxic evaluation of novel quinozalinone derivatives with substituted benzimidazole in position 3 Elham Taherian, Ghadamali Khodarahmi, Marzieh Khajouei, Farshid Hassanzadeh, Nasim Dana Research in Pharmaceutical Sciences 2019 14(3):247-254 Quinazolinone and benzimidazole are both fused heterocyclic compounds which have shown valuable biological properties including cytotoxic, antibacterial, and antifungal activities. In this study, a series of novel quinazolinone derivatives substituted with benzimidazole were synthesized in two parts. In the first part 2 - phenyl - 1H - benzimidazol - 6 - amine (4) was synthesized from the reaction of 4-nitro-o-phenylenediamine and benzoic acid. In the second part, new 3-(2-phenyl-1H benzoimidazol-5-yl)- 3H-quinazolin-4-one derivatives (8a-8f) were also prepared. Finally compound 4 was reacted with the different benzoxazinone derivatives (8a-8f) to give the target compounds. The structures of the synthesized compounds were confirmed by IR and 1HNMR. Cytotoxic activities of the final compounds were assessed at 100, 200, 300, 400, and 500 μM against MCF-7 and HeLa cell lines using the MTT colorimetric assay. Almost all compounds exhibited good cytotoxic activity against both cell lines. Compound 9d demonstrated the highest cytotoxic activity against MCF7 and Hela cell lines with IC50 70 μM and 50 μM, respectively.

The regulatory effect of saffron stigma on the gene expression of the glucose metabolism key enzymes and stress proteins in streptozotocin-induced diabetic rats Maryam Motamedrad, Alireza Shokouhifar, Mina Hemmati, Maryam Moossavi Research in Pharmaceutical Sciences 2019 14(3):255-262 Oxidative stress plays a crucial role in the pathogenesis of hyperglycemia mediated complications. Since a great number of researches have reported antioxidant features of saffron, this study investigated the antioxidant effect of saffron stigma extract (SSE) in streptozotocin-induced diabetic rats. Twenty eight diabetic male Wistar rats were divided in four groups containing: two diabetic groups receiving 25 and 100 mg/kg SSE respectively, one diabetic group receiving glibenclamide (0.6 mg/kg) and one diabetic control group receiving normal saline. Seven healthy adult male Wistar rats were also used as normal control group. After treatment (21 days), fasting blood glucose, insulin, oxidative stress markers, and pancreatic regeneration were assessed. The gene expression level of heat shock factor1, heat shock protein 27, and heat shock protein 70, also glucokinase (GK), and glucose 6-phosphatase (G6Pase) were determined using real-time polymerase chain reaction (RT-PCR). SSE in high dose (100 mg/kg) reduced fasting blood glucose (8.3 ± 0.4 mmol/L) compared with diabetic control (24.6 ± 1.2 mmol/L) (P < 0.05). Furthermore, SSE in high dose increased insulin level compared with diabetic control group (12.7 ± 0.6 vs 7.1 ± 0.3 μϋ/mL). RT-PCR analysis revealed decline in mRNA levels of stress proteins and G6Pase and increase in mRNA level of GK in treatment diabetic groups compared with diabetic control group. Data showed antioxidant and antidiabetic effects of SSE through altering insulin release and glucose metabolism pathways. Hypoglycemic potential of SSE may be due to change in GK and G6Pase enzymes expression. These findings provide a basis for the therapeutic potential of saffron in treatment of diabetes.

Phytochemical analysis and antiproliferative activity of the aerial parts of Scrophularia subaphylla Abbas Delazar, Solmaz Asnaashari, Elhameh Nikkhah, Parina Asgharian Research in Pharmaceutical Sciences 2019 14(3):263-272 Scrophularia subaphylla (S. subaphylla) L., a medicinal plant from the Scrophulariaceae family, has been reported to possess potential profits in the treatment and prophylaxis of different diseases. Some phenolic compounds in this genus have been displayed decent effects on different types of cancer via multiple mechanisms. The current study aimed to bioassay guided isolation of cytotoxic constituents from the aerial parts of S. subaphylla against breast (MCF-7) and colon (HT-29) cancer cell lines as well as normal cells (L929). Different extracts of S. subaphylla were acquired by Soxhlet apparatus and then subjected to brine shrimp lethality test and MTT assay for assessing their cytotoxic characteristics. Cytotoxic extract subjected to further phytochemical fractionation using solid phase extraction, reversed-phase high pressure liquid chromatography (RP-HPLC), and one dimensional nuclear magnetic resonance (1D-NMR) spectroscopy. The biological activity of the isolated pure components, verbascoside and 3´ O rhamnosyl -4´ O para coumaryl 7- hydroxyl salidroside, was assessed using MTT assay against MCF-7 and HT-29 carcinoma cells. Two known phenylpropanoid compounds were isolated from this species. Their structures were elucidated by spectroscopic data (using 1H-NMR and 13C-NMR) and compared with the previous literature. Both pure compounds in comparison with control group demonstrated significant antiproliferative activity against cancerous cells (P < 0.001). In our study, verbascoside and its derivative could inhibit proliferation of cancerous cells without any side effects on normal cells.

Vitex rotundifolia fractions induce apoptosis in human breast cancer cell line, MCF-7, via extrinsic and intrinsic pathways Gul-e-Saba Chaudhry, Rehmat Jan, Habsah Mohamad, Tengku Sifzizul Tengku Muhammad Research in Pharmaceutical Sciences 2019 14(3):273-285 Breast cancer is amongst frequently diagnosed cancer type throughout the world. Due to reduced efficacy of current chemotherapeutics, several natural products have been screened for better alternatives. The cytotoxic activity of fractions prepared from leaves extract of Vitex rotundifolia (V. rotundifolia) on human breast cancer cell line, MCF-7 was studied. The fractions F1, F2, F3, and F5 of V. rotundifolia produced concentration-dependent cytotoxic effects on MCF-7 cell line. The relative potential of cytotoxicity of the fractions on MCF-7 cell line was found to be F3 > F2 > F5 > F1. The active fractions induce apoptosis in MCF-7 cell line determined by annexin V base assay. The phosphatidylserine externalization and the presence of DNA fragmentation in treated cells confirms the early and late apoptosis in treated cells. The V. rotundifolia fractions induced apoptosis by both pathways; extrinsic pathways via activation of caspase-8 and intrinsic pathways through enhanced bax/bcl-2 ratio and activation of caspase-3/7 and caspase-9 proapoptotic proteins. Furthermore, chemical profiling indicates various phenolic, flavonoids, and terpenoids compounds in the active fractions. Thus, V. rotundifolia might be a suitable candidate to investigate further and develop molecular targeted cancer therapeutics by understanding the fundamental mechanisms involved in the regulation of cell death in cancer cells.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Datta Meghe Institute of Medical Sciences University

Review of current global evidences for prevention of coronary heart disease Meenakshi Khapre, Vartika Saxena Journal of Datta Meghe Institute of Medical Sciences University 2019 14(1):1-5 India is experiencing epidemiologic transition with sharp increase in coronary heart disease (CHD). Fatality rate of CHD is alarmingly high leading to the most common cause of premature mortality in 2016. There is the growing burden of coronary risk factors owing to rapid urbanization and changes in lifestyle, including diabetes mellitus (DM), hypertension, dyslipidemia, smoking, alcohol consumption, dietary patterns, central obesity physical inactivity, and psychological factors. These risk factors attribute 90% of CHD in population. The global evidences of preventive strategies is being reviewed in this paper with the aim to get the glimpse of study on CHD and find gaps in the research.

To assess the utility of proliferative marker Ki-67 in surface epithelial ovarian tumor Sheronica Laishram, Vivek Gupta, Arvind Bhake, Akanksha Wankhede, Deepika Agrawal Journal of Datta Meghe Institute of Medical Sciences University 2019 14(1):6-10 Background: Surface epithelial ovarian tumor (SEOT) accounts for more than 90% of all the ovarian tumors and are the most lethal one. Cellular proliferation plays a significant role in the clinical behavior and aggressiveness of ovarian tumor. Proliferative activity of the tumor can be assessed using the proliferative marker Ki-67, which has both diagnostic and prognostic values. Aim and Objective: The aim and objective of this study was to assess the expression of proliferative marker Ki-67 in various SEOT and correlate its level of expression with clinicopathological parameters including the International Federation of Gynecology and Obstetrics (FIGO) staging and preoperative CA-125 level. Materials and Methods: The study was a cross-sectional and observational study carried out in the Department of Pathology, JNMC, Sawangi, Wardha, over 2 years. It included 74 patients with surgically resected specimen of SEOT. Ki-67 immunohistochemistry was performed in all the 74 cases, and the percentage of immunopositive cells was expressed as Ki-67 labeling index (Ki-67 LI). Results: Out of 74 cases, 54 were benign and 20 were malignant which comprised serous and mucinous histological subtypes. Ki-67 expression was found to be positive only in malignant tumors (Ki-67 LI >1%). High Ki-67 LI was associated with high-grade serous cystadenocarcinoma (48.5%), advanced FIGO staging (40.5%), and high CA-125 levels. However, there was no association between Ki-67 LI and histological subtype. Conclusion: Ki-67 is a cost-effective proliferative marker. Therefore, immunohistochemical assessment of Ki-67 expression can be included in routine histopathological report of SEOT for diagnosis and prognostication which will help in better understanding of the biologic behavior of the tumor and modifying treatment strategies.

To correlate histopathological changes and transvaginal sonography findings in the endometrium of patients with abnormal uterine bleeding Akanksha Wankhade, Sunita Vagha, Samarth Shukla, Arvind Bhake, Sheronica Laishram, Deepika Agrawal, Naincy Rastogi, Madhuri Wankhade Journal of Datta Meghe Institute of Medical Sciences University 2019 14(1):11-15 Background: Menstrual ailments are the common manifestation to call for medical visits among women of heavy menstrual bleeding of procreative age. Abnormal uterine bleeding (AUB) affects up to 30% of females in the society. Aim and Objective: The aim of this study was to establish the role of histopathological diagnosis of uterine lesions in patients of AUB and to correlate the transvaginal sonography (TVS) findings with histopathological examination. Materials and Methods: A observational and analytical study was carried out in 120 patients of AUB. All the patients underwent TVS, followed by a histopathological examination of specimens obtained from either D and C or hysterectomy. Results: Menorrhagia was the most common clinical finding. Mean endometrial thickness measured by TVS was 10.15 ± 3.86. Proliferative endometrium (28.33%) was the most frequent finding in histopathological examination, followed by endometrial hyperplasia comprised of 20.83%. Hyperplasia and carcinoma both had a low sensitivity of 36% and 50%, respectively, on TVS compared with histopathology. Conclusion: According to the histopathological diagnosis based on biopsy or D and C, the treatment plan is formulated and the surgery is planned. Hence, even the prognosis depends upon the histopathological examination, TVS is only the initial screening tool for AUB. We advised the clinicians not to rule out these entities only on the basis of TVS.

Impact of Living (Surface) Anatomy module as continuous professional development program for practicing physiotherapists Bincy M George, Satheesha B Nayak, Prem Venketesan, Sapna Marpalli, Mohandas K. G Rao Journal of Datta Meghe Institute of Medical Sciences University 2019 14(1):16-21 Background: It is often presumed that physiotherapists need to be thorough in their knowledge in gross anatomy prior to learning new skills or therapeutic techniques. We implemented a Living (Surface) Anatomy module for physiotherapists, prior to the teaching of therapeutic techniques, in one of the continuous professional development (CPD) programs as a supportive venture for their clinical practice. The present study intended to evaluate the impact of a CPD program on reinforcing practicing physiotherapists' knowledge, skills, and attitude for their clinical practice. Methods: A 1-day workshop was conducted on living (surface) anatomy for practicing physiotherapists (n = 27) through a CPD program. This training included manual muscle testing and body painting of selected muscles of trunk and limbs. Pre- and post-tests were conducted to analyze the impact of the module on improvement in participants' knowledge and skills. In addition, participants were requested to respond to a questionnaire (15 items) on a 5-point Likert scale. Results: Analysis of the pre- and post-test scores revealed a significant increase (34.6%) in surface anatomy knowledge. Majority of the participants opined that the workshop was organized effectively (100%) and the modules helped them to become aware of the lacunae in their knowledge (100%). They also echoed that they realized the need for continuous self-directed learning (100%) and responded that they would attempt to apply whatever they learned through the workshop in their clinical practice (96%). The overall satisfaction score reported by the participants was 9, on a rating scale ranging from 1 to 10 (1 = very poor; 10 = excellent). Conclusion: The CPD was well received by the participants, as evident from their feedback. The present study results demonstrated that the CPD had a positive impact on the participants' knowledge, skills, and attitude.

Profile of urinary tract infection in a rural tertiary care hospital: Two-year cross-sectional study Priyansh Bhayani, Rajendra Rawekar, Shilpa Bawankule, Sunil Kumar, Sourya Acharya, Abhay Gaidhane, Mahalaqua Nazli Khatib Journal of Datta Meghe Institute of Medical Sciences University 2019 14(1):22-26 Aim: The aim of this study was to study the profile of urinary tract infection (UTI) in patients admitted to the medicine department. Settings and Design: This was a cross-sectional study done in a rural tertiary care hospital conducted for a period of 2 years from September 2016 to September 2018. Materials and Methods: All the patients who were admitted (irrespective of the diagnosis at the time of admission) with onset of fever after 48 h of admission, and patients with catheter-associated UTI (CAUTI) and non-CAUTI were defined using the Centers for Disease Control and Prevention guidelines. Statistical Analysis: Statistical analysis was done using descriptive and inferential statistics using Chi-square test and Student's unpaired t-test, and software used in the analysis were SPSS 22.0 version (IBM, USA) and GraphPad Prism 6.0 version (Graphpad software, Inc. California, USA) and P < 0.05 is considered as level of significance. Results: Eighty-four patients developed UTI, the most common organism causing UTI was Escherichia coli. The risk factors associated with CAUTI were higher age, prolonged duration of catheterization, diabetes, and chronic kidney disease. The risk factors associated with non-CAUTI were higher age and benign prostate hyperplasia. The risk factors associated with mortality were prolonged duration of catheterization and diabetes. Twelve patients (14.28%) with CAUTI succumbed in the ICU to their primary illness. Conclusions: Diabetic and elderly patients are at high risk of developing UTI and patients with CAUTI had higher mortality and morbidity.

Dermatoglyphics: A prediction tool for malocclusion Smitha Sammith Shetty, Gloria Su Mi Li, Nurul Ashiqin Binti Babji, Liyana Syatrah Binti Mohd Yusof, Nicholas Ngieng Jiun Yang, Teong Dun Jun, Kuhan Magandran Journal of Datta Meghe Institute of Medical Sciences University 2019 14(1):27-30 Introduction: Dermatoglyphics has proved to have a potential role in predicting the anomalies related to orofacial regions. Aim: The aim of the present study was to explore an association if any, between the dermatoglyphic patterns and type of malocclusion among the Malaysian dental and medical students. Materials and Methods: A total of 104 Malaysian dental and medical students were included in the study. The fingerprints and palm prints were recorded to analyze the type of pattern. Occlusion status was clinically assessed using Angle's classification of malocclusion. Results: Statistically significant association was seen between the left thumb ridge pattern and type of malocclusion. Individuals with loop ridge pattern on their left thumb showed high frequency of Class I normal occlusion and Class III malocclusion, and those with whorl ridge pattern were witnessed to have Class I malocclusion. Conclusion: Dermatoglyphics serves to strengthen the diagnostic impression of malocclusion at an early age and hence can aid in predicting malocclusion and plan preventive and interceptive orthodontics in pediatric patients.

Role of sonoelastography in diagnosing endometrial lesions: Our initial experience Gulam Marfani, Suresh Vasant Phatak, Kaustubh Anil Madurwar, Samida Samad Journal of Datta Meghe Institute of Medical Sciences University 2019 14(1):31-35 Context: Real-time elastography is a novel and dynamic imaging technique that is based on the softness or hardness of tissues or organs of interest under the appropriate compression and can be used with conventional ultrasonography (USG) probes after performing grayscale imaging and Doppler USG. Aims: The aim was to analyze the role of sonoelastography in diagnosing endometrial lesions. Subjects and Methods: A prospective study was conducted from August 2016 to 2018. 30 females were included who underwent sonographic examination. Diagnoses were made and later elastograms were obtained. Strain ratios were calculated and the final diagnosis was compared to histopathological diagnoses to evaluate the role of sonoelastography in diagnosing endometrial pathologies. Statistical Analysis Used: Statistical analysis was done be using descriptive and inferential statistic's using chi square test, students unpaired test, sensitivity and specificity and software used in the analysis were SPSS 22.0 version and graft pad prism 6.0 version. Results: Of the total 30 patients, 5 cases were misdiagnosed on USG compared to 1 on elastography which was of atypical endometrial hyperplasia. Sensitivity, specificity, and diagnostic accuracy of ultrasound were found to be 90.28%, 80%, and 88.5%, respectively. Sensitivity, specificity, and diagnostic accuracy of sonography with elastography were 93.06%, 86.67%, and 91.95%, respectively, showing better results. Conclusions: Sonography coupled with elastography showed better results and can be used to avoid dependency on computed tomography and magnetic resonance imaging avoiding radiation exposures and high cost, especially in a developing country like India, or unnecessary surgical interventions can also be avoided.

Awareness of tuberculosis control program among health-care workers in a tertiary hospital, South India Satyavamsi Gadde, T Jaya Chandra Journal of Datta Meghe Institute of Medical Sciences University 2019 14(1):36-38 Objectives: The objective of the study is to access the awareness of tuberculosis control program (TCP) among health-care workers (HCWs) in a tertiary hospital and to compare the knowledge on TCP between HCWs and the public. Materials and Methods: The participants were provided with printed, multiple-choice questionnaire, containing 28 questions and options to mark the correct answer. All the questions were provided with “not aware” option also. The results were tabulated and analyzed by giving 1 for correct answer, −1 for wrong answer, and 0 for not aware option. The Mann–ANOVA test was used to find the statistical difference. Results: The mean average of scores was 18.52 in the test group and − 0.12 in the control group. Statistical mean significant difference was observed between the groups (P < 0.05). Conclusion: Awareness among the public and HCWs is important for the success of Revised National Tuberculosis Control Programme (RNTCP). To create the awareness in the public, it has to get advertised in cinema theaters, local channels, and newspapers. For awareness among HCWs, scientific updates should be advertised frequently in the journals and symposiums/seminars should be organized regularly by RNTCP.

A rare case of bilateral multiple ovarian dermoids with uterine fibroid and ectopic kidney Suvarna Satish Deshpande, Suresh Vasant Phatak Journal of Datta Meghe Institute of Medical Sciences University 2019 14(1):39-41 Ovarian dermoid cysts are made up of solid, cystic, and fat tissue arising from two of the three germ layers. The incidence of they being bilateral is rare and accounts for 10%–15%. A 42-year-old female came with chief complaints of increased bleeding during menses and pain in the abdomen. Ultrasonography revealed echogenic lesion with heterogeneous echotexture in both the ovaries with internal echogenic strands within which was s/o bilateral dermoid cyst. The patient had a left ectopic renal kidney on contrast-enhanced computed tomography of the abdomen; there was well–defined, rounded, mixed-density mass lesion seen in the pelvis showing fat density, areas of calcification (Rokitansky protuberance), soft tissue, and fluid components. After postoperative and histopathological correlation, it was found to be bilateral dermoid.

Plexiform unicystic ameloblastoma with adenoid differentiation: An unusual finding Monal Yuwanati, Ravi Dande, Amol Ramchandra Gadbail, Shailesh Gondivkar Journal of Datta Meghe Institute of Medical Sciences University 2019 14(1):42-44 Unicystic ameloblastoma (UA) shows clinical and radiologic characteristics of an odontogenic cyst, but histologically shows a typical ameloblastomatous epithelial lining part of the cyst cavity, with or without luminal and/or mural tumor proliferation. Very few cases were reported with variation in histological pattern but rarely with adenoid differentiation. Keeping this in mind, we here report a case report of plexiform UA with adenoid differentiation in maxilla.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Magnetic Resonance Imaging

MRI acoustic noise-modulated computer animations for patient distraction and entertainment with application in pediatric psychiatric patients Publication date: September 2019 Source: Magnetic Resonance Imaging, Volume 61 Author(s): Refaat E. Gabr, Giovana B. Zunta-Soares, Jair C. Soares, Ponnada A. Narayana Abstract Purpose To reduce patient anxiety caused by the MRI scanner acoustic noise. Material and methods We developed a simple and low-cost system for patient distraction using visual computer animations that were synchronized to the MRI scanner's acoustic noise during the MRI exam. The system was implemented on a 3T MRI system and tested in 28 pediatric patients with bipolar disorder. The patients were randomized to receive noise-synchronized animations in the form of abstract animations in addition to music (n = 13, F/M = 6/7, age = 10.9 ± 2.5 years) or, as a control, receive only music (n = 15, F/M = 7/8, age = 11.6 ± 2.3 years). After completion of the scans, all subjects answered a questionnaire about their scan experience and the perceived scan duration. Results The scan duration with multisensory input (animations and music) was perceived to be ~15% shorter than in the control group (43 min vs. 50 min, P < 0.05). However, the overall scan experience was scored less favorably (3.9 vs. 4.6 in the control group, P < 0.04). Conclusions This simple system provided patient distraction and entertainment leading to perceived shorter scan times, but the provided visualization with abstract animations was not favored by this patient cohort.

Using amide proton transfer to identify cervical squamous carcinoma/adenocarcinoma and evaluate its differentiation grade Publication date: September 2019 Source: Magnetic Resonance Imaging, Volume 61 Author(s): Nan Meng, Jing Wang, Jing Sun, Wenling Liu, Xuejia Wang, Minghuan Yan, Akshay Dwivedi, Dandan Zheng, Kaiyu Wang, Dongming Han Abstract Purpose To explore the possibility of using amide proton transfer-weighted imaging (APTWI) for the identification and diagnosis of cervical squamous carcinoma (CSC), cervical adenocarcinoma (CA) and different levels of CSC. Materials and methods Seventy-six patients with newly diagnosed uterine cervical cancer (UCC) were studied prior to treatment, including 20 with poorly differentiated (Grade 3) CSC, 23 with moderately differentiated (Grade 2) CSC, 17 with well-differentiated (Grade 1) CSC, and 16 with CA (13 with poorly differentiated (Grade 3) CA and 3 with moderately differentiated (Grade 2) CA). Differences in the magnetization transfer ratio at 3.5 ppm (MTRasym (3.5 ppm)) were identified between CSC and CA and between high-level (Grade 3) CSC and low-level (Grade 2 and Grade 1) CSC, as well as among all three grades of CSC differentiation. Receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic thresholds and performance of the parameters. Spearman correlation analysis was used to examine the correlation between the MTRasym (3.5 ppm) and histological grade. Results The MTRasym (3.5 ppm) in CA was higher than that in CSC (P = 0.001). The MTRasym (3.5 ppm) in high-level CSC was higher than that in low-level CSC (P = 0.001). The MTRasym (3.5 ppm) was positively correlated with the grade of CSC differentiation (r = 0.498, P = 0.001). The MTRasym (3.5 ppm) in Grade 3 CSC was higher than that in Grade 2 and Grade 1 CSC (P = 0.02/0.01). No significant difference in the MTRasym (3.5 ppm) was found between Grade 2 CSC and Grade 1 CSC (P = 0.173). The area under the ROC curve (AUC) for the MTRasym (3.5 ppm) in distinguishing CSC and CA was 0.779, with a cut-off, sensitivity, and specificity of 2.97%, 60.0% and 82.5%, respectively. The AUC for distinguishing high-/low-level CSC was 0.756, with a cut-off, sensitivity, and specificity of 3.29%, 68.8% and 83.3%, respectively. Conclusion APTWI may be a useful technique for the identification and diagnosis of CSC, CA and different levels of CSC, which may have an important impact on clinical strategies for treating patients with UCC.

7T GRE-MRI signal compartments are sensitive to dysplastic tissue in focal epilepsy Publication date: September 2019 Source: Magnetic Resonance Imaging, Volume 61 Author(s): Kiran Thapaliya, Javier Urriola, Markus Barth, David C. Reutens, Steffen Bollmann, Viktor Vegh Abstract Ultra-high field magnetic resonance imaging data obtained using a multi-echo gradient echo sequence has been shown to contain information on tissue microstructure. Quantitative assessment of water fraction, relaxation time and frequency shift using multi-compartment signal modelling may help improve our understanding of diseases and disorders affecting the human brain. In this study, we explored tissue microstructure information by analysing voxel compartment water fraction and frequency shifts derived from 7 T multi-echo gradient recalled echo MRI data. We aimed to test whether the parameters of a three compartment model could distinguish the normal cortex from the cortex affected by focal cortical dysplasia. We compartmentalised normal and dysplastic cortical regions in patients diagnosed with focal cortical dysplasia. We found the frequency shift parameter of the shortest T2⁎ signal compartment to be sensitive to regions of dysplastic tissue. We conclude that mathematical modelling of echo time dependent gradient recalled echo MRI signals in patients with focal cortical dysplasia can potentially delineate cortical areas that have undergone microstructural changes in comparison to normal tissue.

Differentiating platinum coated brachytherapy seeds and gold fiducial markers with varying off-resonant frequency offsets Publication date: July 2019 Source: Magnetic Resonance Imaging, Volume 60 Author(s): Evan McNabb, Raimond Wong, Michael D. Noseworthy Abstract Purpose To develop an off-resonant frequency filtered method to selectively differentiate between implanted gold fiducial markers and platinum coated brachytherapy seeds. Materials and methods The magnetic susceptibilities for gold fiducial markers and brachytherapy seeds differ in magnitude and also in their signs, resulting in B0-field inhomogeneity patterns with opposite main lobes. A pulse sequence used to localize brachytherapy seeds with positive contrast, centre-out radial sampling with off-resonance reception (co-RASOR), was used to reconstruct images with a range of off-resonant frequency offsets. The proposed method utilizes two frequency filters to selectively reconstruct maximum intensity projections through band-pass regions where each seed has its maximal localized hyperintensity. Seeds were simulated and then placed in gel and tissue phantoms to validate the technique using orthogonal 2D slices with seeds both parallel and perpendicular to the B0-field. Results Dual-plane 2D co-RASOR sequences were reconstructed off-resonance with applied frequency filters to create two projections displaying each seed, which were then colour-coded to negative and positive frequencies. Phantom validation showed that each seed contains its maximal CNR in opposing frequency regions as predicted. Local maxima can also appear in both negative and positive frequency regions. The relative difference between the signal of each seed and these local maxima ranged from 1.19 to 3.73, and an image threshold was determined in all cases. Tissue validation showed the technique differentiates seeds correctly and is limited by the hyperintensity patterns observed in the co-RASOR method. Conclusions Dual-plane co-RASOR offers sub-millimetre positive contrast from implanted seeds that contain unique off-resonant frequency maxima, which frequency filters can selectively differentiate.

MEGA-PRESS and PRESS measure oxidation of glutathione in a phantom Publication date: July 2019 Source: Magnetic Resonance Imaging, Volume 60 Author(s): Maiken K. Brix, Gerard E. Dwyer, Alexander R. Craven, Renate Grüner, Ralph Noeske, Lars Ersland Abstract Purpose Investigate the possibility of measuring changes in glutathione (GSH) concentration using the MRS PRESS and MEGA-PRESS sequences by tracking the natural oxidation of GSH, and to examine the accuracy of the two methods. Methods 122 GSH edited MEGA-PRESS and PRESS acquisitions were acquired on a "braino" based phantom +3.0 mM GSH during a period of 11 days. All spectra were analyzed in LCModel. (The MEGA-PRESS data were first preprocessed in Matlab). Degradation curves were modeled. A one year follow-up on the same phantom and measurements from a similar phantom without GSH and one pure GSH phantom were also included. Results Both MEGA-PRESS and PRESS showed degradation of the measured GSH signal. Modeling the exponential decay of the GSH signal in MEGA-PRESS and PRESS gave for t = 0; 2.9 i.u. for MEGA-PRESS and 2.3 i.u. for PRESS. As t increased, the GSH concentration converged to zero for MEGA-PRESS but not for PRESS (0.7 i.u.). GSH for the one year follow up were 0.0 i.u. for MEGA-PRESS and 0.6 i.u. for PRESS. Similar phantom without GSH yielded 0.0 i.u. for both MEGA-PRESS and PRESS. Conclusion It is possible to measure changes in GSH concentration in a phantom using both PRESS and MEGA-PRESS techniques, however the PRESS spectrum appears to include oxidized GSH (GSSG). In addition, GSH edited MEGA-PRESS measurement gives more precise values at lower GSH concentrations.

Non-contrast-enhanced magnetic resonance imaging for visualization and quantification of endovascular aortic prosthesis, their endoleaks and aneurysm sacs at 1.5 T Publication date: July 2019 Source: Magnetic Resonance Imaging, Volume 60 Author(s): Mona Salehi Ravesh, Patrick Langguth, Julian Andreas Pfarr, Jasper Schupp, Jens Trentmann, Ioannis Koktzoglou, Robert R. Edelman, Joachim Graessner, Andreas Greiser, David Hautemann, Anja Hennemuth, Marcus Both, Olav Jansen, Jan-Bernd Hövener, Jost Philipp Schäfer Abstract Purpose After an endovascular aortic aneurysm repair (EVAR), a follow-up at 1, 6 and every 12 months is recommended for remainder of the patient's life. The diagnostic standard methods for diagnosing endoleaks and visualization of aneurysms in EVAR-patients are: invasive digital subtraction angiography (DSA), contrast enhanced (CE) computed tomographic angiography (CE-CTA), and magnetic resonance angiography (CE-MRA). These techniques, however, require the use of iodine- or gadolinium-based contrast agents with rare, but possibly life threatening side effects such as renal impairment, thyrotoxicosis and allergic reactions, nephrogenic systemic fibrosis, and cerebral gadolinium deposition. The aim of this prospective study was to compare a non-contrast-enhanced MRI protocol (consist of four MRI methods) with DSA and CE-CTA for visualization and quantification of endovascular aortic prosthesis, their endoleaks and aneurysms. Material and methods Eight patients (mean age 76.8 ± 4.9 years, 63% male), whose thoracic, abdominal, or iliac aneurysms were treated with different endovascular prosthesis and suffered from type I–V endoleaks, were examined on a 1.5 Tesla MR system. Quiescent-interval slice selective MR angiography (QISS-MRA), 4-dimensional (4D)-flow MRI, T1- and T2-mapping, as well as DSA and CE-CTA were used for the visualization and quantification of endoprosthesis, endoleaks, and aneurysms in these patients. Results QISS-MRA provided good visualization of endoleaks and comparable quantification of aneurysm size with respect to CE-CTA and DSA. The 4D-flow MRI provided additional information about the wall shear stress, which could not be determined using DSA. In contrast to CE-CTA, T1- and T2-mapping provided detailed information about heterogeneous areas within an aneurysm sac. Conclusions Compared to DSA and CE-CTA, the proposed MRI methods provide improved anatomical and functional information for various types of endoprostheses and endoleaks. In addition, hemodynamic parameters of the aorta and information on the content of aneurysm sac are provided as well. Within the frame of personalized medicine, the personalized diagnosis enabled by this non-CE MRI protocol is the foundation for a personalized and successful treatment.

Assessment of transplant renal artery stenosis with diffusion-weighted imaging: A preliminary study Publication date: July 2019 Source: Magnetic Resonance Imaging, Volume 60 Author(s): Min Fan, Xuefeng Ni, Yanjun Li, Jinsong Chen, Dongrui Cheng, Donghong Shi, Xiaozhou He, Jiqiu Wen Abstract Objective To characterize capillary perfusion and tissue diffusion changes in transplant renal artery stenosis (TRAS) with diffusion-weighted imaging (DWI). Materials & methods We retrospectively identified 30 patients with non-contrast enhanced magnetic resonance angiography-proven TRAS. Another 20 kidney transplant recipients without TRAS were prospectively recruited to serve as control group. DWI parameters were compared among various groups with one-way analysis of variance and post hoc Tukey test. Additionally, DWI parameters were compared in 7 severe TRAS patients before and after successful angioplasty using paired Student t-test. Receiver-operating characteristic (ROC) curves were generated to evaluate the diagnostic performance of various DWI parameters. Results All DWI parameters of renal cortex and medulla were not statistically different between normal allografts and allografts with mild TRAS. Nonetheless, cortical total apparent diffusion coefficient (ADCT) of allografts with moderate TRAS was significantly decreased compared with normal allografts. All cortical and medullary DWI parameters were significantly reduced in severe TRAS compared with normal allografts. ROC curve analysis indicated ADCT could identify severe TRAS with 93.8% sensitivity, 82.4% specificity and an area under the curve of 0.930. ADCT increased significantly after successful angioplasty while it showed no significant change in a patient with unsuccessful angioplasty. Conclusion DWI is a robust technique that revealed no tissue diffusion and perfusion impairment in mild TRAS. ADCT has good sensitivity and specificity for identifying patients with severe TRAS. DWI is potentially an alternative radiologic biomarker for assessing microstructural and perfusion alterations in TRAS. DWI is useful in detecting renal functional recovery following successful angioplasty.

Compressed sensing reconstruction of 7 Tesla 23Na multi-channel breast data using 1H MRI constraint Publication date: July 2019 Source: Magnetic Resonance Imaging, Volume 60 Author(s): Sebastian Lachner, Olgica Zaric, Matthias Utzschneider, Lenka Minarikova, Štefan Zbýň, Bernhard Hensel, Siegfried Trattnig, Michael Uder, Armin M. Nagel Abstract Purpose To reduce acquisition time and to improve image quality in sodium magnetic resonance imaging (23Na MRI) using an iterative reconstruction algorithm for multi-channel data sets based on compressed sensing (CS) with anatomical 1H prior knowledge. Methods An iterative reconstruction for 23Na MRI with multi-channel receiver coils is presented. Based on CS it utilizes a second order total variation (TV(2)), adopted by anatomical weighting factors (AnaWeTV(2)) obtained from a high-resolution 1H image. A support region is included as additional regularization. Simulated and measured 23Na multi-channel data sets (n = 3) of the female breast acquired at 7 T with different undersampling factors (USF = 1.8/3.6/7.2/14.4) were reconstructed and compared to a conventional gridding reconstruction. The structural similarity was used to assess image quality of the reconstructed simulated data sets and to optimize the weighting factors for the CS reconstruction. Results Compared with a conventional TV(2), the AnaWeTV(2) reconstruction leads to an improved image quality due to preserving of known structure and reduced partial volume effects. An additional incorporated support region shows further improvements for high USFs. Since the decrease in image quality with higher USFs is less pronounced compared to a conventional gridding reconstruction, proposed algorithm is beneficial especially for higher USFs. Acquisition time can be reduced by a factor of 4 (USF = 7.2), while image quality is still similar to a nearly fully sampled (USF = 1.8) gridding reconstructed data set. Conclusion Especially for high USFs, the proposed algorithm allows improved image quality for multi-channel 23Na MRI data sets.

Demonstration of full tensor current density imaging using ultra-low field MRI Publication date: July 2019 Source: Magnetic Resonance Imaging, Volume 60 Author(s): P. Hömmen, J.-H. Storm, N. Höfner, R. Körber Abstract Direct imaging of impressed dc currents inside the head can provide valuable conductivity information, possibly improving electro-magnetic neuroimaging. Ultra-low field magnetic resonance imaging (ULF MRI) at μT Larmor fields can be utilized for current density imaging (CDI). Here, a measurable impact of the magnetic field BJ, generated by the impressed current density J, on the MR signal is probed using specialized sequences. In contrast to high-field MRI, the full tensor of BJ can be derived without rotation of the subject in the scanner, due to a larger flexibility in the sequence design. We present an ULF MRI setup based on a superconducting quantum interference device (SQUID), which is operating at a noise level of 380 aT Hz−1/2 and capable of switching all imaging fields within a pulse sequence. Thereby, the system enables zero-field encoding, where the full tensor of BJ is probed in the absence of other magnetic fields. 3D CDI is demonstrated on phantoms with different geometries carrying currents of approximately 2 mA corresponding to current densities between 0.45 and 8 A/m2. By comparison to an in vivo acquired head image, we provide insights to necessary improvements in signal-to-noise ratio.

Accelerated positive contrast MRI of interventional devices using parallel compressed sensing imaging Publication date: July 2019 Source: Magnetic Resonance Imaging, Volume 60 Author(s): Samira Vafay Eslahi, Jim Ji Abstract Susceptibility-based magnetic resonance imaging (MRI) method can image small MR-compatible devices with positive contrast. However, the relatively long data acquisition time required by the method hinders its practical applications. This study presents a parallel compressive sensing technique with a modified fast spin echo to accelerate data acquisition for the susceptibility-based positive contrast MRI. The method integrates the generalized autocalibrating partially parallel acquisitions and the compressive sensing techniques in the reconstruction algorithm. MR imaging data acquired from several phantoms containing interventional devices such as biopsy needles, stent, and brachytherapy seeds, used for validating the proposed technique. The results show that it can speed up data acquisition by a factor of about five while preserving the quality of the positive contrast images.

Alexandros Sfakianakis
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alsfakia@gmail.com