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There are a few empirical studies that examine the portrayal of the Middle East and its people in young children's picture books. Many of these books depict Muslim life and celebrations without delving into the specificities of each Middle Eastern country. This study, which focuses on Iran as a non-Arab Muslim majority Middle Eastern country, investigates how Iran and its diverse cultures are represented in children's picture books published in North America. The analysis was conducted on a sample of 27 picture books written in English between 2000 and 2021, targeting children aged three to nine. The findings reveal that a significant number of these books revolve around Nowruz celebrations (the Persian New Year) or ancient Persia, often presented through popular folktales. These findings underscore the need for books that depict the contemporary lives of Iranians, both within and outside the country, through narratives and illustrations.

Background: Fetal echocardiography is a useful tool for diagnosing fetuses with congenital heart diseases, and it is best to be conducted between 17 and 19 weeks of gestational age. However, fetal echocardiography can be performed at other ages of pregnancy for a variety of reasons. This study describes one fetus with pulmonary valvar stenosis based on the fetal echocardiogram in the uterus.Case report: This study describes one fetus with pulmonary valve stenosis based on the fetal echocardiogram in the uterus. We referred the family to a hospital with neonatal intensive care unit admission. After birth, we followed her serially and confirmed pulmonary valve stenosis, which increased in severity after two months. Subsequently, we performed a percutaneous balloon valvuloplasty.Conclusion: Our findings showed that some cardiac defects could vary in severity during pregnancy and post-birth. There was clear evidence that pulmonary valvar stenosis was a lesion developed during the fetus's lifetime to tolerate the lesion. Although pulmonary stenosis progressed in the early months after birth, it was easily treated through balloon angioplasty.

A 9-year-old girl with signs and symptoms of acute toxic myocarditis and cardiogenic shock with elevated cardiac enzymes was admitted to the Critical Care Unit (CCU) of our hospital with an ejection fraction of 25%. The patient was managed with supportive care and the administration of polyvalent antivenom and inotropes, and after 8 days, she was discharged without any complication with normal ejection fraction. Toxic myocarditis can be a result of scorpion envenomation. After two months of follow-up, the patient recovered completely and medications were discontinued.

Purpose: Pituitary adenoma surgery is a complex procedure due to critical adjacent neurovascular structures, variations in size and extensions of the lesions, and potential hormonal imbalances. The integration of artificial intelligence (AI) and machine learning (ML) has demonstrated considerable potential in assisting neurosurgeons in decision-making, optimizing surgical outcomes, and providing real-time feedback. This scoping review comprehensively summarizes the current status of AI/ML technologies in pituitary adenoma surgery, highlighting their strengths and limitations. Methods: PubMed, Embase, Web of Science, and Scopus were searched following the PRISMA-ScR guidelines. Studies discussing the use of AI/ML in pituitary adenoma surgery were included. Eligible studies were grouped to analyze the different outcomes of interest of current AI/ML technologies. Results: Among the 2438 identified articles, 44 studies met the inclusion criteria, with a total of seventeen different algorithms utilized across all studies. Studies were divided into two groups based on their input type: clinicopathological and imaging input. The four main outcome variables evaluated in the studies included: outcome (remission, recurrence or progression, gross-total resection, vision improvement, and hormonal recovery), complications (CSF leak, readmission, hyponatremia, and hypopituitarism), cost, and adenoma-related factors (aggressiveness, consistency, and Ki-67 labeling) prediction. Three studies focusing on workflow analysis and real-time navigation were discussed separately. Conclusion: AI/ML modeling holds promise for improving pituitary adenoma surgery by enhancing preoperative planning and optimizing surgical strategies. However, addressing challenges such as algorithm selection, performance evaluation, data heterogeneity, and ethics is essential to establish robust and reliable ML models that can revolutionize neurosurgical practice and benefit patients. [ABSTRACT FROM AUTHOR]

Introduction: In psychiatric settings, aggressive events frequently occur during therapy. These events, which tend to threaten the safety of the patient and the staff, can lead to the enforcement of compulsory measures such as the isolation or restraining of the patient. The use of a proper standard scale to register aggression can facilitate the assessment and control of aggression and help reduce its frequency and severity. The review of literature revealed only a few studies conducted on aggressive behavior in hospitalized psychiatric patients in Iran and showed that the lack of a reliable and valid observation scale for registering in psychiatric settings. The aim of this study is to evaluate the validity and reliability of the Staff Observation Aggression Scale—Revised (SOAS-R). Methods: This psychometric study of the scale was conducted to determine the validity and reliability of the SOAS-R. The validation of the scale was assessed on the basis of 319 aggressive events in the psychiatric wards of the Baqiyatallah and Roozbeh hospitals. Convenience sampling was used for subject selection. Psychometric properties of SOAS-R were studied in two stages. First, the standard scale was translated according to the International Quality of Life Assessment (IQOLA) translation methodology. The face validity, content , and construct validity of the translated version were then determined. The construct validity of the scale was assessed by comparing the known groups. Results: The internal consistency of the whole scale was 0.99. The intra-class correlation coefficients (ICC) were 0.852–0.995 while kappa coefficient was 0.43 to 0.65 for the different aspects of the SOAS-R. The validity of the scale was concurrently assessed by using the Visual Analogue Scale (VAS), with a Spearman-Brown correlation coefficient of 0.90. Conclusion: These results showed a favourable validity and reliability for the Persian version of the SOAS-R for the assessment of aggressive behaviour in psychiatric patients.

Background: Thalassemia patients need repeated transfusion that lead to increased blood ferritin level and iron overload in the heart and liver. Because the roles of hepcidin antimicrobial peptide (HAMP) and hemocromatosis protein (HFE) in iron metabolism have been confirmed, this study investigated the effects of these gene's polymorphisms on blood ferritin levels and iron overload in the heart and liver in patients with beta thalassemia major Materials and Methods: This cross-sectional study was conducted on 91 patients referring to the Hajar Hospital in Shahrekord, Iran in 2015. After the blood samples were collected, the ferritin levels were measured, DNA was extracted from the blood cells, and the types of polymorphisms were determined using PCR-RFLP. Data of MRI T2* in the heart and liver were drawn from the patients' medical files. Data analysis was conducted by t-test, chi-square test, Fisher's exact test, and Pearson correlation coefficient. Results: There was no significant correlation between blood ferritin level and c.-582 A>G polymorphisms of hepcidin gene (p=0.58), and H63D of HFE gene (p=0.818). In addition, there was no significant association between the polymorphisms and heart and liver MRI, but there was a significant association between blood ferritin level and qualitative heart and liver MRI (r=-0.34, p=0.035 and r=-0.001, p=0.609, respectively). Conclusion: In patients with β-thalassemia major, the presence of c.-582A>G HAMP and H63D HFE polymorphisms is not effective on blood ferritin level and iron overload in the heart and liver in the studied region.

Some of the harms of real estate and land transactions relying on property ownership and normal documents are: land grabbing, shrinking of agricultural land, threat to food security, weakness in managing crises and natural disasters, increase in administrative and judicial corruption, occurrence of fraud, bribery, forgery and etc. In order to solve these harms, the theory of real estate and land registration in the registration system has been proposed. Regarding this theory, there are two challenges of "the legitimacy of the system" and "the monopolization of real estate and land transactions in the system". In this essay, with a descriptive and analytical method, the belief has been strengthened that based on jurisprudential rules and principles, the registration system in question is legitimate and in the assumption that three conditions are met: the existence of a system that leads to certainty of ownership, the accusation of the market and the disruption of people's livelihood in the assumption of referring to the Amarat, real estate and land transactions based on the Amarat of property are void, and in order to accurately identify the owners, the buyer and seller should only refer to the registration system. Therefore, it is necessary to make the transaction of real estate and land according to the registration system become a law, and in the event of a conflict, this system takes precedence over all the property Amarat. [ABSTRACT FROM AUTHOR]

The ultimate goal of child custody is the realization of children's benefits and to keep them out of harm.Therefore, if the parents lack base qualifications and abilities, the child custody will be deprived of them. Also in the article 1173 of the Civil Code, child custody deprivation from its holder is considered. Since one of the qualifications of child's supervisor is his (her) physical health, this paper, by analysis of jurists' opinions, is going to examine the impact of illnesses on child custody. It further surveys that if the guardian has an infectious illness, endangering child's physical health, or he (she) is not able to keep the child due to an incurable disease, his (her) custody will be void. But if the guardian be able to prevent the spread of illness to the child or does the affairs resulting the maintenance and upbringing of the child through an agent for example, child custody will be constant according to the legal rule.

Abstract Background & Aim: The occupational nature of health profession is such that employees in these occupations are exposed to various stressors which threaten their mental health. We aimed to investigate the influence of stress management and communication skills training on the improvement of mental health of nurses and hospital staff. Material & Methods: It was a quasi-experimental study. The sample included 32 nurses and other hospital staff of Baqiyatallah hospital in Tehran that were first recruited by voluntary sampling and then were randomly assigned to experimental and control groups. Stress management and communication skills training program based on the cognitive-behavioral theory was performed during a 16 hours period. Data was collected by Depression Anxiety Stress Scale (DASS) before and after the intervention and was analyzed by descriptive statistics and analysis of covariance using SPSS-PC (v. 18). Results: The results of the analysis of covariance indicated that the intervention has significantly reduced stress and anxiety in the experimental group compared to the control group (P< 0/01). However, no significant difference was seen in terms of depression (P=0/861). Conclusion: By reducing symptoms of stress and anxiety, stress management and communication skills training based on cognitive-behavior theory can improve mental health of nurses and hospital staff. Accordingly, using this program by health managers to improve mental health of their staff is recommended.

Background Anal squamous cell carcinoma (SCCA) is an uncommon malignancy with a rising incidence that has a high cure rate in its early stages. There is an unmet need for a reliable method to monitor response to treatment and assist in surveillance. Circulating tumor DNA (ctDNA) testing has shown great promise in other solid tumors for monitoring disease progression and detecting relapse in real time. This study aimed to determine the feasibility and use of personalized and tumor-informed ctDNA testing in SCCA. Patients and Methods We analyzed real-world data from 251 patients (817 plasma samples) with stages I-IV SCCA, collected between 11/5/19 and 5/31/22. The tumor genomic landscape and feasibility of ctDNA testing was examined for all patients. The prognostic value of longitudinal ctDNA testing was assessed in patients with clinical follow-up (N = 37). Results Whole-exome sequencing analysis revealed PIK3CA as the most commonly mutated gene, and no associations between mutations and stage. Anytime ctDNA positivity and higher ctDNA levels (MTM/mL) were associated with metastatic disease (P =. 004). For 37 patients with clinical follow-up, median follow-up time was 21.0 months (range: 4.1-67.3) post-diagnosis. For patients with stages I-III disease, anytime ctDNA-positivity after definitive treatment was associated with reduced DFS (HR: 28.0; P =. 005). Conclusions Our study demonstrates the feasibility of personalized and tumor-informed ctDNA testing as an adjunctive tool in patients with SCCA as well as potential use for detection of molecular/minuteimal residual disease, and relapse during surveillance. Prospective studies are needed to better evaluate the use of ctDNA testing in this indication. [ABSTRACT FROM AUTHOR]

Tourist actrvrties are not distributed homogeneously in space; rather, certain activities are concentrated in specific points or areas. Numerous factors account for this pattern. Climate is one of the geophysical factors that make up geographical space, contributing to the environmental conditions that facilitate or hinder human settlement in general and tourism activities in particular. Therefore, climate is an important criterion for locating tourism centers, helping to determine how an area is to be used. It has been argued that local climatology and succession of different weather types influence the location of resorts, the calendar of tourist activities, the use and efficiency of the infrastructure, and the return on investments. The impact of climate ad well as climatic changes upon Snow skiing is being pursued as another objective of this study. As such, evaluation of Ski-resort potentials in Iran was conducted as an applied nature of this study. This study suggests that optimum areas regarding snow skiing are basically Elborz ranges between Tehran and Mazandran and to a lesser extent Charmahal province nested in Zagrous mountain.

Background: Fetal echocardiography is a useful tool for diagnosing fetuses with congenital heart diseases, and it is best to be conducted between 17 and 19 weeks of gestational age. However, fetal echocardiography can be performed at other ages of pregnancy for a variety of reasons. This study describes one fetus with pulmonary valvar stenosis based on the fetal echocardiogram in the uterus. Case report: This study describes one fetus with pulmonary valve stenosis based on the fetal echocardiogram in the uterus. We referred the family to a hospital with neonatal intensive care unit admission. After birth, we followed her serially and confirmed pulmonary valve stenosis, which increased in severity after two months. Subsequently, we performed a percutaneous balloon valvuloplasty. Conclusion: Our findings showed that some cardiac defects could vary in severity during pregnancy and post-birth. There was clear evidence that pulmonary valvar stenosis was a lesion developed during the fetus's lifetime to tolerate the lesion. Although pulmonary stenosis progressed in the early months after birth, it was easily treated through balloon angioplasty. [ABSTRACT FROM AUTHOR]

Background: Thalassemia patients need repeated transfusion that lead to increased blood ferritin level and iron overload in the heart and liver. Because the roles of hepcidin antimicrobial peptide (HAMP) and hemocromatosis protein (HFE) in iron metabolism have been confirmed, this study investigated the effects of these gene's polymorphisms on blood ferritin levels and iron overload in the heart and liver in patients with beta thalassemia major. Materials and Methods: This cross-sectional study was conducted on 91 patients referring to the Hajar Hospital in Shahrekord, Iran in 2015. After the blood samples were collected, the ferritin levels were measured, DNA was extracted from the blood cells, and the types of polymorphisms were determined using PCR-RFLP. Data of MRI T2* in the heart and liver were drawn from the patients' medical files. Data analysis was conducted by t-test, chi-square test, Fisher's exact test, and Pearson correlation coefficient. Results: There was no significant correlation between blood ferritin level and c.-582 A>G polymorphisms of hepcidin gene (p=0.58), and H63D of HFE gene (p=0.818). In addition, there was no significant association between the polymorphisms and heart and liver MRI, but there was a significant association between blood ferritin level and qualitative heart and liver MRI (r=-0.34, p=0.035 and r=-0.001, p=0.609, respectively). Conclusion: In patients with β-thalassemia major, the presence of c.-582A>G HAMP and H63D HFE polymorphisms is not effective on blood ferritin level and iron overload in the heart and liver in the studied region. [ABSTRACT FROM AUTHOR]

We determined whether the approved myelofibrosis drug ruxolitinib (Jakafi®), an inhibitor of Janus kinases 1/2 (JAK1 and JAK2), could be repurposed as an anti-cancer agent for solid tumors. Ruxolitinib synergistically interacted with dual ERBB1/2/4 inhibitors to kill breast as well as lung, ovarian and brain cancer cells. Knock down of JAK1/2 or of ERBB1/2/3/4 recapitulated on-target drug effects. The combination of (ruxolitinib + ERBB1/2/4 inhibitor) rapidly inactivated AKT, mTORC1, mTORC2, STAT3, and STAT5, and activated eIF2α. In parallel, the drug combination reduced expression of MCL-1, BCL-XL, HSP90, HSP70, and GRP78, and increased expression of Beclin1. Activated forms of STAT3, AKT, or mTOR prevented the drug-induced decline in BCL-XL, MCL-1, HSP90, and HSP70 levels. Over-expression of chaperones maintained AKT/ mTOR activity in the presence of drugs and protected tumor cells from the drug combination. Expression of dominant negative eIF2α S51A prevented the increase in Beclin1 expression and protected tumor cells from the drug combination. Loss of mTOR activity was associated with increased ATG13 S318 phosphorylation and with autophagosome formation. Autophagosomes initially co-localized with mitochondria and subsequently with lysosomes. Knock down of Beclin1 suppressed: drug-induced mitophagy; the activation of the toxic BH3 domain proteins BAX and BAK; and tumor cell killing. Knock down of apoptosis-inducing factor (AIF) protected tumor cells from the drug combination, whereas blockade of caspase 9 signaling did not. The drug combination released AIF into the cytosol and increased nuclear AIF: eIF3A co-localization. A 4-day transient exposure of orthotopic tumors to (ruxolitinib + afatinib) profoundly reduced mammary tumor growth over the following 35 days. Re-grown tumors exhibited high levels of BAD S112 phosphorylation and activation of ERK1/2 and NFκB. Our data demonstrate that mitophagy is an essential component of (ruxolitinib + ERBB inhibitor) lethality and that this drug combination should be explored in a phase I trial in solid tumor patients. [ABSTRACT FROM AUTHOR]

Prior tumor cell studies have shown that the drugs sorafenib (Nexavar) and regorafenib (Stivarga) reduce expression of the chaperone GRP78. Sorafenib/regorafenib and the multi-kinase inhibitor pazopanib (Votrient) interacted with sildenafil (Viagra) to further rapidly reduce GRP78 levels in eukaryotes and as single agents to reduce Dna K levels in prokaryotes. Similar data were obtained in tumor cells in vitro and in drug-treated mice for: HSP70, mitochondrial HSP70, HSP60, HSP56, HSP40, HSP10, and cyclophilin A. Prolonged 'rafenib/sildenafil treatment killed tumor cells and also rapidly decreased the expression of: the drug efflux pumps ABCB1 and ABCG2; and NPC1 and NTCP, receptors for Ebola/Hepatitis A and B viruses, respectively. Pre-treatment with the 'Rafenib/sildenafil combination reduced expression of the Coxsackie and Adenovirus receptor in parallel with it also reducing the ability of a serotype 5 Adenovirus or Coxsackie virus B4 to infect and to reproduce. Sorafenib/pazopanib and sildenafil was much more potent than sorafenib/pazopanib as single agents at preventing Adenovirus, Mumps, Chikungunya, Dengue, Rabies, West Nile, Yellow Fever, and Enterovirus 71 infection and reproduction. 'Rafenib drugs/pazopanib as single agents killed laboratory generated antibiotic resistant E. coli which was associated with reduced Dna K and Rec A expression. Marginally toxic doses of 'Rafenib drugs/pazopanib restored antibiotic sensitivity in pan-antibiotic resistant bacteria including multiple strains of blakpc Klebsiella pneumoniae. Thus, Dna K is an antibiotic target for sorafenib, and inhibition of GRP78/Dna K has therapeutic utility for cancer and for bacterial and viral infections. J. Cell. Physiol. 230: 2552-2578, 2015. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

We examined the interaction between OSU-03012 (also called AR-12) with phosphodiesterase 5 (PDE5) inhibitors to determine the role of the chaperone glucose-regulated protein (GRP78)/BiP/HSPA5 in the cellular response. Sildenafil (Viagra) interacted in a greater than additive fashion with OSU-03012 to kill stem-like GBM cells. Treatment of cells with OSU-03012/sildenafil: abolished the expression of multiple oncogenic growth factor receptors and plasma membrane drug efflux pumps and caused a rapid degradation of GRP78 and other HSP70 and HSP90 family chaperone proteins. Decreased expression of plasma membrane receptors and drug efflux pumps was dependent upon enhanced PERK-eIF2α-ATF4-CHOP signaling and was blocked by GRP78 over-expression. In vivo OSU-03012/sildenafil was more efficacious than treatment with celecoxib and sildenafil at killing tumor cells without damaging normal tissues and in parallel reduced expression of ABCB1 and ABCG2 in the normal brain. The combination of OSU-03012/sildenafil synergized with low concentrations of sorafenib to kill tumor cells, and with lapatinib to kill ERBB1 over-expressing tumor cells. In multiplex assays on plasma and human tumor tissue from an OSU-03012/sildenafil treated mouse, we noted a profound reduction in uPA signaling and identified FGF and JAK1/2 as response biomarkers for potentially suppressing the killing response. Inhibition of FGFR signaling and to a lesser extent JAK1/2 signaling profoundly enhanced OSU-03012/sildenafil lethality. J. Cell. Physiol. 230: 1982-1998, 2015. © 2015 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

The chaperone GRP78/Dna K is conserved throughout evolution down to prokaryotes. The GRP78 inhibitor OSU-03012 (AR-12) interacted with sildenafil (Viagra) or tadalafil (Cialis) to rapidly reduce GRP78 levels in eukaryotes and as a single agent reduce Dna K levels in prokaryotes. Similar data with the drug combination were obtained for: HSP70, HSP90, GRP94, GRP58, HSP27, HSP40 and HSP60. OSU-03012/sildenafil treatment killed brain cancer stem cells and decreased the expression of: NPC1 and TIM1; LAMP1; and NTCP1, receptors for Ebola/Marburg/Hepatitis A, Lassa fever, and Hepatitis B viruses, respectively. Pre-treatment with OSU-03012/sildenafil reduced expression of the coxsakie and adenovirus receptor in parallel with it also reducing the ability of a serotype 5 adenovirus or coxsakie virus B4 to infect and to reproduce. Similar data were obtained using Chikungunya, Mumps, Measles, Rubella, RSV, CMV, and Influenza viruses. OSU-03012 as a single agent at clinically relevant concentrations killed laboratory generated antibiotic resistant E. coli and clinical isolate multi-drug resistant N. gonorrhoeae and MRSE which was in bacteria associated with reduced Dna K and Rec A expression. The PDE5 inhibitors sildenafil or tadalafil enhanced OSU-03012 killing in N. gonorrhoeae and MRSE and low marginally toxic doses of OSU-03012 could restore bacterial sensitivity in N. gonorrhoeae to multiple antibiotics. Thus, Dna K and bacterial phosphodiesterases are novel antibiotic targets, and inhibition of GRP78 is of therapeutic utility for cancer and also for bacterial and viral infections. J. Cell. Physiol. 230: 1661-1676, 2015. © 2014 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

The present studies determined whether clinically relevant phosphodiesterase 5 (PDE5) inhibitors interacted with a clinically relevant NSAID, celecoxib, to kill tumor cells. Celecoxib and PDE5 inhibitors interacted in a greater than additive fashion to kill multiple tumor cell types. Celecoxib and sildenafil killed ex vivo primary human glioma cells as well as their associated activated microglia. Knock down of PDE5 recapitulated the effects of PDE5 inhibitor treatment; the nitric oxide synthase inhibitor L-NAME suppressed drug combination toxicity. The effects of celecoxib were COX2 independent. Over-expression of c-FLIP-s or knock down of CD95/FADD significantly reduced killing by the drug combination. CD95 activation was dependent on nitric oxide and ceramide signaling. CD95 signaling activated the JNK pathway and inhibition of JNK suppressed cell killing. The drug combination inactivated mTOR and increased the levels of autophagy and knock down of Beclin1 or ATG5 strongly suppressed killing by the drug combination. The drug combination caused an ER stress response; knock down of IRE1α/XBP1 enhanced killing whereas knock down of eIF2α/ATF4/CHOP suppressed killing. Sildenafil and celecoxib treatment suppressed the growth of mammary tumors in vivo. Collectively our data demonstrate that clinically achievable concentrations of celecoxib and sildenafil have the potential to be a new therapeutic approach for cancer. J. Cell. Physiol. 230: 1115-1127, 2015. © 2014 Wiley Periodicals, Inc., A Wiley Company [ABSTRACT FROM AUTHOR]

Background: Perinatal asphyxia is an important cause of mortality and permanent neurological and developmental deficit. Early and accurate diagnosis would help to establish the likely prognosis and may also help in determining the most appropriate treatment. Studies in experimental animal models suggest that a protein called Hsp70 may be a good and potentially useful marker of cellular stress that may be clinically useful in determining the presence of neonatal asphyxia. Objectives: Regarding the importance of early and accurate diagnosis of asphyxia, we conducted this study, which is the first investigation of the comparison of the serum Hsp70 antigen level between asphyxiated and healthy infants. Patients and Methods: In this observational study, the serum concentrations of Hsp70 antigen were compared between neonates suffering from perinatal asphyxia (n = 50) and normal neonates (n = 51). The inclusion criteria for the cases were neonates who had reached term and had at least two clinical criteria of asphyxia. Exclusion criteria were babies with gestational age < 37 weeks, infants with congenital abnormalities or positive blood culture. Exclusion criteria in this group were the requirement to hospital stay during first week of the life or babies whose mothers had difficulties during pregnancy or delivery. Term neonates without major anomalies who had asphyxia during delivery were enrolled in the first six hours after delivery, and control group consisted of healthy term neonates without problems and normal delivery process in the first week of life. The cord blood was taken during labor to measure Hsp70 antigen level by using an in-house ELISA (The enzyme-linked immunosorbent assay). Results: The median values of serum anti Hsp70 titers were significantly higher in asphyxiated neonates compared with non-asphyxiated neonates (0.36 [0.04 - 1.14] vs 0.24 [0.01 - 0.63]). At cutoff point = 0.3125 ng/mL, sensitivity was 58% and specificity 76% based on ROC curve. Conclusions: A significant difference between the serum concentrations of Hsp70 of the control and patient group was observed in this study. It is inferred serum concentrations of Hsp70 antigen may be a useful marker for the early diagnosis of that prenatal hypoxia. [ABSTRACT FROM AUTHOR]

The present studies were to determine whether the multi-kinase inhibitor sorafenib or its derivative regorafenib interacted with the ERBB1/ERBB2 inhibitor lapatinib to kill CNS tumor cells. In multiple CNS tumor cell types sorafenib and lapatinib interacted in a greater than additive fashion to cause tumor cell death. Tumor cells lacking PTEN, and anoikis or lapatinib resistant cells were as sensitive to the drug combination as cells expressing PTEN or parental cells, respectively. Similar data were obtained using regorafenib. Treatment of brain cancer cells with [sorafenib + lapatinib] enhanced radiation toxicity. The drug combination increased the numbers of LC3-GFP vesicles; this correlated with a reduction in endogenous LC3II, and p62 and LAMP2 degradation. Knock down of Beclin1 or ATG5 significantly suppressed drug combination lethality. Expression of c-FLIP-s, BCL-XL, or dominant negative caspase 9 reduced drug combination toxicity; knock down of FADD or CD95 was protective. Expression of both activated AKT and activated MEK1 or activated mTOR was required to strongly suppress drug combination lethality. As both lapatinib and sorafenib are FDA approved agents, our data argue for further determination as to whether lapatinib and sorafenib is a useful glioblastoma therapy. J. Cell. Physiol. 229: 131-139, 2014. © 2014 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]