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We show that the gradient force generated by the near field of a chiral nanoparticle carries information about its chirality. On the basis of this physical phenomenon we propose a new microscopy technique that enables the prediction of spatial features of chirality of nanoscale samples by exploiting the photoinduced optical force exerted on an achiral tip in the vicinity of the test specimen. The tip-sample interactive system is illuminated by structured light to probe both the transverse and longitudinal (with respect to the beam propagation direction) components of the sample's magnetoelectric polarizability as the manifestation of its sense of handedness, i.e., chirality. We specifically prove that although circularly polarized waves are adequate to detect the transverse polarizability components of the sample, they are unable to probe the longitudinal component. To overcome this inadequacy and probe the longitudinal chirality, we propose a judiciously engineered combination of radially and azimuthally polarized beams as optical vortices possessing pure longitudinal electric and magnetic field components along their vortex axis, respectively. The proposed technique may benefit branches of science such as stereochemistry, biomedicine, physical and material science, and pharmaceutics.

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Light-matter interactions enable the perception of specimen properties such as its shape and dimensions by measuring the subtle differences carried by an illuminating beam after interacting with the sample. However, major obstacles arise when the relevant properties of the specimen are weakly coupled to the incident beam, for example when measuring optical magnetism and chirality. To address this challenge we propose the idea of detecting such weakly-coupled properties of matter through the photo-induced force, aiming at developing photo-induced magnetic or chiral force microscopy. Here we review our pursuit consisting of the following steps: (1) Development of a theoretical blueprint of a magnetic nanoprobe to detect a magnetic dipole oscillating at an optical frequency when illuminated by an azimuthally polarized beam via the photo-induced magnetic force; (2) Conducting an experimental study using an azimuthally polarized beam to probe the near fields and axial magnetism of a Si disk magnetic nanoprobe, based on photo-induced force microscopy; (3) Extending the concept of force microscopy to probe chirality at the nanoscale, enabling enantiomeric detection of chiral molecules. Finally, we discuss difficulties and how they could be overcome, as well as our plans for future work.

The distribution of fitness effects of new mutations plays a central role in evolutionary biology. Estimates of the distribution of fitness effect from experimental mutation accumulation lines are compromised by the complete linkage disequilibrium between mutations in different lines. To reduce the linkage disequilibrium, we constructed 2 sets of recombinant inbred lines from a cross of 2 Caenorhabditis elegans mutation accumulation lines. One set of lines ("RIAILs") was intercrossed for 10 generations prior to 10 generations of selfing; the second set of lines ("RILs") omitted the intercrossing. Residual linkage disequilibrium in the RIAILs is much less than in the RILs, which affects the inferred distribution of fitness effect when the sets of lines are analyzed separately. The best-fit model estimated from all lines (RIAILs + RILs) infers a large fraction of mutations with positive effects (∼40%); models that constrain mutations to have negative effects fit much worse. The conclusion is the same using only the RILs. For the RIAILs, however, models that constrain mutations to have negative effects fit nearly as well as models that allow positive effects. When mutations in high linkage disequilibrium are pooled into haplotypes, the inferred distribution of fitness effect becomes increasingly negative-skewed and leptokurtic. We conclude that the conventional wisdom-most mutations have effects near 0, a handful of mutations have effects that are substantially negative, and mutations with positive effects are very rare-is likely correct, and that unless it can be shown otherwise, estimates of the distribution of fitness effect that infer a substantial fraction of mutations with positive effects are likely confounded by linkage disequilibrium., Competing Interests: Conflicts of interest The author(s) declare no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Genetics Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Although three-dimensional (3D) genome structures are altered in cancer cells, little is known about how these changes evolve and diversify during cancer progression. Leveraging genome-wide chromatin tracing to visualize 3D genome folding directly in tissues, we generated 3D genome cancer atlases of murine lung and pancreatic adenocarcinoma. Our data reveal stereotypical, non-monotonic, and stage-specific alterations in 3D genome folding heterogeneity, compaction, and compartmentalization as cancers progress from normal to preinvasive and ultimately to invasive tumors, discovering a potential structural bottleneck in early tumor progression. Remarkably, 3D genome architectures distinguish histologic cancer states in single cells, despite considerable cell-to-cell heterogeneity. Gene-level analyses of evolutionary changes in 3D genome compartmentalization not only showed compartment-associated genes are more homogeneously regulated, but also elucidated prognostic and dependency genes in lung adenocarcinoma and a previously unappreciated role for polycomb-group protein Rnf2 in 3D genome regulation. Our results demonstrate the utility of mapping the single-cell cancer 3D genome in tissues and illuminate its potential to identify new diagnostic, prognostic, and therapeutic biomarkers in cancer., Competing Interests: S.W., M.L., M.D.M., S.J., and S.S.A. are inventors on a patent applied for by Yale University related to this work. M.D.M. received research funding from a Genentech supported AACR grant and an honorarium from Nested Therapeutics. The remaining authors declare no competing interests.

Importance: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignant tumor, and durable disease control is rare with the current standard of care, even for patients who undergo surgical resection., Objective: To assess whether neoadjuvant modified 5-fluorouracil, leucovorin, oxaliplatin, and irinotecan (mFOLFIRINOX) leads to early control of micrometastasis and improves survival., Design, Setting, and Participants: This open-label, single-arm, phase 2 nonrandomized controlled trial for resectable PDAC was conducted at the Yale Smilow Cancer Hospital from April 3, 2014, to August 16, 2021. Pancreatic protocol computed tomography was performed at diagnosis to assess surgical candidacy. Data were analyzed from January to July 2023., Interventions: Patients received 6 cycles of neoadjuvant mFOLFIRINOX before surgery and 6 cycles of adjuvant mFOLFIRINOX. Whole blood was collected and processed to stored plasma for analysis of circulating tumor DNA (ctDNA) levels. Tumors were evaluated for treatment response and keratin 17 (K17) expression., Main Outcomes and Measures: The primary end point was 12-month progression-free survival (PFS) rate. Additional end points included overall survival (OS), ctDNA level, tumor molecular features, and K17 tumor levels. Survival curves were summarized using Kaplan-Meier estimator., Results: Of 46 patients who received mFOLFIRINOX, 31 (67%) were male, and the median (range) age was 65 (46-80) years. A total of 37 (80%) completed 6 preoperative cycles and 33 (72%) underwent surgery. A total of 27 patients (59%) underwent resection per protocol (25 with R0 disease and 2 with R1 disease); metastatic or unresectable disease was identified in 6 patients during exploration. Ten patients underwent surgery off protocol. The 12-month PFS was 67% (90% CI, 56.9-100); the median PFS and OS were 16.6 months (95% CI, 13.3-40.6) and 37.2 months (95% CI, 17.5-not reached), respectively. Baseline ctDNA levels were detected in 16 of 22 patients (73%) and in 3 of 17 (18%) after 6 cycles of mFOLFIRINOX. Those with detectable ctDNA levels 4 weeks postresection had worse PFS (hazard ratio [HR], 34.0; 95% CI, 2.6-4758.6; P = .006) and OS (HR, 11.7; 95% CI, 1.5-129.9; P = .02) compared with those with undetectable levels. Patients with high K17 expression had nonsignificantly worse PFS (HR, 2.7; 95% CI, 0.7-10.9; P = .09) and OS (HR, 3.2; 95% CI, 0.8-13.6; P = .07)., Conclusions and Relevance: This nonrandomized controlled trial met its primary end point, and perioperative mFOLFIRINOX warrants further evaluation in randomized clinical trials. Postoperative ctDNA positivity was strongly associated with recurrence. K17 and ctDNA are promising biomarkers that require additional validation in future prospective studies., Trial Registration: ClinicalTrials.gov Identifier: NCT02047474.

Introduction: Identifying clinical factors that increase the risk of mortality in COVID-19 patients is crucial. This enables targeted screening, optimizing treatment, and prevention of severe complications, ultimately reducing death rates. This study aimed to develop prediction models for the death of patients (i.e., survival or death) during the COVID-19 pandemic in Shiraz, exploring the main influencing factors., Method: We conducted a retrospective cohort study using hospital-based records of 1030 individuals diagnosed with COVID-19, who were hospitalized for treatment between March 21, 2021, and March 21, 2022, in Shiraz, Iran. Variables related to the final outcome were selected based on criteria and univariate logistic regression. Hierarchical multiple logistic regression and classification and regression tree (CART) models were utilized to explore the relationships between potential influencing factors and the final outcome. Additionally, methods were employed to identify the high-risk population for increased mortality rates during COVID-19. Finally, accuracy was evaluated the performance of the models, with the area under the receiver operator characteristic curve(AUC), sensitivity, and specificity metrics., Results: In this study, 558 (54.2%) individuals infected with COVID-19 died. The final model showed that the type of medicine antiviral (OR: 11.10, p = 0.038) than reference (antiviral and corticosteroid), and discharge oxygen saturation(O2) (OR: 1.10, p < 0.001) had a positive association with the chance of survival, but other variables were not considered as predictive variables. Predictive models for the final outcome(death) achieved accuracies ranging from 81 to 87% for hierarchical multiple logistic regression and from 87 to 94% for the CART model. Therefore, the CART model performed better than the hirerical multiple logistic regression model., Conclusion: These findings firstly elucidate the incidence and associated factors of the outcome (death) among patients in Shiraz, Iran. Furthermore, we demonstrated that antiviral medication alone (without corticosteroids) and high O2 increase the survival chances of COVID patients., (© 2024. The Author(s).)

Background: In heart failure, signaling downstream the β2-adrenergic receptor is critical. Sympathetic stimulation of β2-adrenergic receptor alters cAMP (cyclic adenosine 3',5'-monophosphate) and triggers PKA (protein kinase A)-dependent phosphorylation of proteins that regulate cardiac function. cAMP levels are regulated in part by PDEs (phosphodiesterases). Several AKAPs (A kinase anchoring proteins) regulate cardiac function and are proposed as targets for precise pharmacology. AKAP12 is expressed in the heart and has been reported to directly bind β2-adrenergic receptor, PKA, and PDE4D. However, its roles in cardiac function are unclear., Methods: cAMP accumulation in real time downstream of the β2-adrenergic receptor was detected for 60 minutes in live cells using the luciferase-based biosensor (GloSensor) in AC16 human-derived cardiomyocyte cell lines overexpressing AKAP12 versus controls. Cardiomyocyte intracellular calcium and contractility were studied in adult primary cardiomyocytes from male and female mice overexpressing cardiac AKAP12 (AKAP12 OX ) and wild-type littermates post acute treatment with 100-nM isoproterenol (ISO). Systolic cardiac function was assessed in mice after 14 days of subcutaneous ISO administration (60 mg/kg per day). AKAP12 gene and protein expression levels were evaluated in left ventricular samples from patients with end-stage heart failure., Results: AKAP12 upregulation significantly reduced total intracellular cAMP levels in AC16 cells through PDE8. Adult primary cardiomyocytes from AKAP12 OX mice had significantly reduced contractility and impaired calcium handling in response to ISO, which was reversed in the presence of the selective PDE8 inhibitor (PF-04957325). AKAP12 OX mice had deteriorated systolic cardiac function and enlarged left ventricles. Patients with end-stage heart failure had upregulated gene and protein levels of AKAP12., Conclusions: AKAP12 upregulation in cardiac tissue is associated with accelerated cardiac dysfunction through the AKAP12-PDE8 axis., Competing Interests: Disclosures H. Qasim was employed by IonOptix LLC following the initial article submission. H. Qasim, M. Rajaei, Y. Xu, and B.K. McConnell have a Provisional Patent Application (no. 63/621 310; Modulation of AKAP12 Signalosome; UH Technology Disclosure ID no. 2024-023). The other authors report no conflicts.

GATA3 and Mammaglobin are often used in the clinic to identify metastases of mammary origin due to their robust and diffuse expression in mammary tissue. However, the expression of these markers has not been well characterized in tumors from African American women. The goal of this study was to characterize and evaluate the expression of GATA3 and mammaglobin breast tumors from African American women and determine their association with clinicopathological outcomes including breast cancer subtypes. Tissue microarrays (TMAs) were constructed from well preserved, morphologically representative tumors in archived formalin-fixed, paraffin-embedded (FFPE) surgical blocks from 202 patients with primary invasive ductal carcinoma. Mammaglobin, and GATA3 expression was assessed using immunohistochemistry (IHC). Univariate analysis was carried out to determine the association between expression of GATA3, mammaglobin and clinicopathological characteristics. Kaplan-Meier estimates of overall survival and disease-free survival were also plotted and a log-rank test performed to compare estimates among groups. GATA3 expression showed statistically significant association with lower grade (p<0.001), ER-positivity (p<0.001), PR-positivity (p<0.001), and the luminal subtype (p<0.001). Mammaglobin expression was also significantly associated with lower grade (p=0.031), ER-positivity (p=0.007), and PR-positivity (p=0.022). There was no association with recurrence-free or overall survival. Our results confirm that GATA3 and mammaglobin demonstrate expression predominantly in luminal breast cancers from African American women. Markers with improved specificity and sensitivity are warranted given the high prevalence of triple negative breast cancer in the group.

We demonstrate experimentally the detection of magnetic force at optical frequencies, defined as the dipolar Lorentz force exerted on a photoinduced magnetic dipole excited by the magnetic component of light. Historically, this magnetic force has been considered elusive since, at optical frequencies, magnetic effects are usually overshadowed by the interaction of the electric component of light, making it difficult to recognize the direct magnetic force from the dominant electric forces. To overcome this challenge, we develop a photoinduced magnetic force characterization method that exploits a magnetic nanoprobe under structured light illumination. This approach enables the direct detection of the magnetic force, revealing the magnetic nearfield distribution at the nanoscale, while maximally suppressing its electric counterpart. The proposed method opens up new avenues for nanoscopy based on optical magnetic contrast, offering a research tool for all-optical spin control and optomagnetic manipulation of matter at the nanoscale.

Caenorhabditis elegans strains with the heat-sensitive mortal germline phenotype become progressively sterile over the course of a few tens of generations when maintained at temperatures near the upper range of C. elegans' tolerance. Mortal germline is transgenerationally heritable, and proximately under epigenetic control. Previous studies have suggested that mortal germline presents a relatively large mutational target and that mortal germline is not uncommon in natural populations of C. elegans. The mortal germline phenotype is not monolithic. Some strains exhibit a strong mortal germline phenotype, in which individuals invariably become sterile over a few generations, whereas other strains show a weaker (less penetrant) phenotype in which the onset of sterility is slower and more stochastic. We present results in which we (1) quantify the rate of mutation to the mortal germline phenotype and (2) quantify the frequency of mortal germline in a collection of 95 wild isolates. Over the course of ∼16,000 meioses, we detected one mutation to a strong mortal germline phenotype, resulting in a point estimate of the mutation rate UMrt≈ 6×10-5/genome/generation. We detected no mutations to a weak mortal germline phenotype. Six out of 95 wild isolates have a strong mortal germline phenotype, and although quantification of the weak mortal germline phenotype is inexact, the weak mortal germline phenotype is not rare in nature. We estimate a strength of selection against mutations conferring the strong mortal germline phenotype s¯≈0.1%, similar to selection against mutations affecting competitive fitness. The appreciable frequency of weak mortal germline variants in nature combined with the low mutation rate suggests that mortal germline may be maintained by balancing selection., (© The Author(s) 2022. Published by Oxford University Press on behalf of Genetics Society of America.)

Background: Our previous study indicated that Potentilla reptans root has a preconditioning effect by its antioxidant and anti-apoptotic effects in an isolated rat heart ischemia/reperfusion (IR) model. In the present study, we investigated the post-conditioning cardio-protective effects of Potentilla reptans and its active substances., Methods: The ethyl acetate fraction of P. reptans root (Et) was subjected to an IR model under 30 min of ischemia and 100 min of reperfusion. To investigate the postconditioning effect, Et was perfused for 15 min at the early phase of reperfusion. RISK/SAFE pathway inhibitors, 5HD and L-NAME, were applied individually 10 min before the ischemia, either alone or in combination with Et during the early reperfusion phase. The hemodynamic factors and ventricular arrhythmia were calculated during the reperfusion. Oxidative stress, apoptosis markers, GSK-3β and SGK1 proteins were assessed at the end of experiments., Results: Et postconditioning (Etpost) significantly reduced the infarct size, arrhythmia score, ventricular fibrillation incidence, and enhanced the hemodynamic parameters by decreasing the MDA level and increasing expression of Nrf2, SOD and CAT activities. Meanwhile, Etpost increased the BCl-2/BAX ratio and decreased Caspase-3 expression. The cardioprotective effect of Etpost was abrogated by L-NAME, Wortmannin (a PI3K/Akt inhibitor), and AG490 (a JAK/STAT3 inhibitor). Finally, Etpost reduced the expression of GSK-3β and SGK1 proteins pertaining to the IR group., Conclusion: P. reptans reveals the post-conditioning effects via the Nrf2 pathway, NO release, and the RISK/SAFE pathway. Also, Etpost decreased apoptotic indexes by inhibiting GSK-3β and SGK1 expressions. Hence, our data suggest that Etpost can be a suitable natural candidate to protect cardiomyocytes during reperfusion injury., (© 2021. The Author(s).)

Background: In recent years, interest in the consumption of ready-to-eat (RTE) food products has been increased in many countries. However, RTE products particularly those prepared by meat may be potential vehicles of antibiotic-resistance foodborne pathogens. Considering kebab and hamburger are the most popular RTE meat products in Iran, this study aimed to investigate the prevalence and antimicrobial resistance of common foodborne pathogens (Escherichia coli, Salmonella spp., Staphylococcus aureus, and Listeria monocytogenes) in raw kebab and hamburger samples collected from fast-food centers and restaurants. Therefore, total bacterial count (TBC), as well as the prevalence rates and antibiogram patterns of foodborne pathogens in the samples were investigated. Also, the presence of antibiotic-resistance genes (bla SHV , bla TEM, bla Z , and mecA) was studied in the isolates by PCR., Results: The mean value of TBC in raw kebab and hamburger samples was 6.72 ± 0.68 log CFU/g and 6.64 ± 0.66 log CFU/g, respectively. E. coli had the highest prevalence rate among the investigated pathogenic bacteria in kebab (70%) and hamburger samples (48%). Salmonella spp., L. monocytogenes, and S. aureus were also recovered from 58, 50, and 36% of kebab samples, respectively. The contamination of hamburger samples was detected to S. aureus (22%), L. monocytogenes (22%), and Salmonella spp. (10%). In the antimicrobial susceptibility tests, all isolates exhibited high rates of antibiotic resistance, particularly against amoxicillin, penicillin, and cefalexin (79.66-100%). The bla TEM was the most common resistant gene in the isolates of E. coli (52.54%) and Salmonella spp. (44.11%). Fourteen isolates (23.72%) of E. coli and 10 isolates (29.41%) of Salmonella spp. were positive for bla SHV . Also, 16 isolates (55.17%) of S. aureus and 10 isolates (27.27%) of L. monocytogenes were positive for mecA gene., Conclusions: The findings of this study showed that raw kebab and hamburger are potential carriers of antibiotic-resistance pathogenic bacteria, which can be a serious threat to public health., (© 2021. The Author(s).)

Important clues about natural selection can be gleaned from discrepancies between the properties of segregating genetic variants and of mutations accumulated experimentally under minimal selection, provided the mutational process is the same in the laboratory as in nature. The base-substitution spectrum differs between C. elegans laboratory mutation accumulation (MA) experiments and the standing site-frequency spectrum, which has been argued to be in part owing to increased oxidative stress in the laboratory environment. Using genome sequence data from C. elegans MA lines carrying a mutation ( mev - 1 ) that increases the cellular titer of reactive oxygen species (ROS), leading to increased oxidative stress, we find the base-substitution spectrum is similar between mev - 1 , its wild-type progenitor (N2), and another set of MA lines derived from a different wild strain (PB306). Conversely, the rate of short insertions is greater in mev - 1 , consistent with studies in other organisms in which environmental stress increased the rate of insertion-deletion mutations. Further, the mutational properties of mononucleotide repeats in all strains are different from those of nonmononucleotide sequence, both for indels and base-substitutions, and whereas the nonmononucleotide spectra are fairly similar between MA lines and wild isolates, the mononucleotide spectra are very different, with a greater frequency of A:T → T:A transversions and an increased proportion of ±1-bp indels. The discrepancy in mutational spectra between laboratory MA experiments and natural variation is likely owing to a consistent (but unknown) effect of the laboratory environment that manifests itself via different modes of mutability and/or repair at mononucleotide loci., (© 2021 Rajaei et al.; Published by Cold Spring Harbor Laboratory Press.)

Background: Oxidative stress is caused by the imbalance occurring between the creation and clearance of the reactive oxygen species (ROS), which is responsible for 30-40% of male infertility. The positive impact of phoenix dactylifera pollen (Date palm pollen, DPP) on the improvement of sperm parameters has been well documented in animal models., Objective: For evaluating the effect(s) of DPP on sperm parameters, ROS levels, expression of antioxidant genes, and activity of antioxidant enzymes of infertile men., Materials and Methods: In this controlled clinical trial, a total of 60 male case with infertility and 20 normospermic fertile men were recruited. Before and after the treatment with DPP, the case were administered 400 mg/kg of gelatinous capsules daily for 30 consecutive days and semen samples were taken. Quantitative real-time polymerase chain reaction was applied for the evaluation of the mRNA expression levels of Nuclear factor erythroid 2-related factor 2( NRF2 ), superoxide dismutase ( SOD2 ), glutathione peroxidase 4( GPX4 ), and catalase ( CAT ) genes., Results: The mRNA expression levels of NRF2, SOD2, GPX4 , and CAT (p < 0.05 for all) and significantly increased after treatment with DPP. The increased expressions of all antioxidant genes and enzymes significantly correlated with improvement in semen parameters including count (p = 0.01), motility (p = 0.05), and morphology (p = 0.01) of sperm. A significant correlation between the alteration of SOD2 gene expression and SOD activity, GPX4 and GPX, and CAT were also observed (p = 0.05)., Conclusion: DPP can increase the expressions of NRF2, GPX4, SOD2 , and CAT genes and also improve the semen quality in infertile men., Competing Interests: Hereby, it is declared that there is no conflict of interest regarding the research., (Copyright © 2021 Fallahi et al.)

Introduction: The purpose of this double-blind clinical trial, was to examine the effect of supplementation with the synbiotic and probiotic on the mental health, quality of life, and anemia in HD patients., Methods: Seventy-five HD patients were randomly assigned to receive the synbiotic ( n = 23) as 15 g of prebiotics, 5 g of probiotic powder containing Lactobacillus acidophilus, Bifidobacterium bifidum, Bifidobacterium lactis , and Bifidobacterium longum (2.7 × 107 CFU/g each); probiotics ( n = 23) as 5 g probiotics similar to the synbiotic group with 15 g of maltodextrin as placebo; and placebo ( n = 19) as 20 g of maltodextrin. Serum hemoglobin (Hb) and albumin (Alb) were measured. Beck depression and anxiety index (BDI/BAI) was used to assess symptoms of depression and anxiety. The health-related quality of life (HRQoL) was assessed using the questionnaire SF-36., Results: From baseline to 12 weeks, synbiotic and probiotic supplementation resulted in a significant decrease in BDI and BAI score in comparison to the placebo ( P < 0.05). Between and intergroup comparison showed no significant changes between the groups in terms of HRQoL. However, the serum Hb level increased significantly in the synbiotic and probiotic group compared to the placebo group ( P < 0.001)., Conclusion: Overall, 12 weeks of synbiotic and probiotic supplementation resulted in an improvement in mental health and anemia compared with the placebo, whereas they failed to enhance the quality of life in HD patients., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Indian Journal of Nephrology.)

Despite all previous studies relating to the mechanism of cirrhotic cardiomyopathy (CCM), the role of cirrhosis on Ischemic Preconditioning (IPC) has not yet been explored. The present study strives to assess the cardioprotective role of IPC in bile duct ligated (BDL) rats as well as the cardioprotective role of Cyclosporin-A (CsA) and Metformin (Met) in CCM. Cirrhosis was induced by bile duct ligation (BDL). Rats' hearts were isolated and attached to a Langendorff Apparatus. The pharmacological preconditioning with Met and CsA was done before the main ischemia. Myocardial infarct size, hemodynamic and electrophysiological parameters, biochemical markers, and apoptotic indices were determined at the end of the experiment. Infarct size, apoptotic indices, arrhythmia score, and incidence of VF decreased significantly in the IPC group in comparison with the I/R group. These significant decreases were abolished in the IPC (BDL) group. Met significantly decreased the infarct size and apoptotic indices compared with I/R (BDL) and normal groups, while CsA led to similar decreases except in the level of caspase-3 and -8. Met and CsA decreased and increased the arrhythmia score and incidence of VF in the BDL groups, respectively. Functional recovery indices decreased in the I/R (BDL) and IPC (BDL) groups. Met improved these parameters. Therefore, the current study depicted that the cardioprotective effect of Met and CsA on BDL rats is mediated through the balance between pAMPK and apoptosis in the mitochondria., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Neuroblastoma is an aggressive pediatric solid tumor with an overall survival rate of <50% for patients with high-risk disease. The majority (>98%) of pathologically-diagnosed neuroblastomas have wild-type p53 with intact functional activity. However, the mouse double minute 2 (MDM2) homolog, an E3 ubiquitin ligase, is overexpressed in neuroblastoma and leads to inhibition of p53. MDM2 also exerts p53-independent oncogenic functions. Thus, MDM2 seems to be an attractive target for the reactivation of p53 and attenuation of oncogenic activity in neuroblastoma., Methods: In this study, we evaluated the anticancer activities and underlying mechanisms of action of SP141, a first-in-class MDM2 inhibitor, in neuroblastoma cell lines with different p53 backgrounds. The findings were confirmed in mouse xenograft models of neuroblastoma., Results: We demonstrate that SP141 reduces neuroblastoma cell viability, induces apoptosis, arrests cells at the G2/M phase, and prevents cell migration, independent of p53. In addition, in neuroblastoma xenograft models, SP141 inhibited MDM2 expression and suppressed tumor growth without any host toxicity at the effective dose., Conclusions: MDM2 inhibition by SP141 results in the inhibition of neuroblastoma growth and metastasis, regardless of the p53 status of the cells and tumors. These findings provide proof-of-concept that SP141 represents a novel treatment option for both p53 wild-type and p53 null neuroblastoma.

Normal-weight obesity (NWO) syndrome is associated with metabolic diseases. The present study aimed to investigate the effects of 12 weeks of a high-protein (HP) v. a standard protein (SP) diet on appetite, anthropometry and body composition in NWO women. In this clinical trial, fifty NWO women were randomly allocated to HP (n 25) or SP (n 25) diet groups. Women in the HP and SP groups consumed 25 and 15 % of their total energy intake from protein for 12 weeks. Weight, fat mass (FM), lean body mass (LBM), waist circumference (WC) and appetite were evaluated at baseline and following their 3-month intervention. After 12 weeks, the LBM was higher in HP compared with no significant changes in the SP group (mean between-group difference = 1·5 kg; 95 % CI 3·1, 0·01; effect size (d) = 0·4). Furthermore, the HP group had lower FM (mean between-group difference -1·1 kg; 95 % CI 1, -3·3; d = -0·2), body fat percentage (BFP) (mean between-group difference -2 %; 95 % CI 0·7, -5·2; d = -0·3) and WC (mean between-group difference -1·4 cm; 95 % CI 0·6, -3·6; d = -0·2) at the end of the study in comparison with the SP group. In both groups, weight and appetite were unchanged over time without significant differences between groups. Twelve weeks of euenergetic diets with different dietary protein contents resulted in no significant weight loss in women with NWO. However, an HP diet significantly improved body composition (LBM, FM, BFP and WC) in this population.

Background: Implementing a cervical cancer prevention program requires an exploration of certain behaviors concerning this disease. This study is aimed to evaluate the psychometrics of a questionnaire that enquired about the factors involved in Precaution Adoption Process Model (PAPM) for cervical cancer among suburban women in Bandar Abbas, south of Iran., Materials and Methods: The primary draft of the questionnaire was developed with a review of the related literature on cervical cancer and the constructs affecting PAPM, with 68 items. The face validity, content validity ratio (CVR), and content validity index (CVI) of the questionnaire were approved by a panel of 10 experts. The internal consistency and test-retest reliability of the questionnaire were estimated too. Field testing sample included 300 women recruited from a women's healthcare center in suburban areas of Bandar Abbas in the south of Iran. Exploratory factor analysis was used to evaluate validity, and Cronbach's alpha coefficient was estimated for reliability., Results: After the face validation, 11 items were eliminated. Once CVR was estimated, two items were discarded. The remaining items had a CVR >0.79. All had a CVI >0.79. Six items were eliminated in the factor analysis. The final questionnaire included 49 items organized in 8 factors including awareness, perceived susceptibility, perceived severity, perceived benefits, perceived barriers, social norms, fear, and self-efficacy. Principal component analysis with varimax rotation indicated eight main components that explained 56.25% of the variance. Reliability assessment showed a good internal consistency for all subscales and the Cronbach's alpha score ranged between 0.82 and 0.90. The test-retest reliability showed that the correlation coefficients (between 0.81 and 0.89) were significant at the 0.01 level for all sub-scales., Conclusions: The final questionnaire was a new instrument comprised the effective constructs of PAPM and had a high reliability and validity. Thus, this questionnaire is recommended to be used to explore and enhance preventive behaviors of cervical cancer., Competing Interests: There are no conflicts of interest., (Copyright: © 2020 Journal of Education and Health Promotion.)

There is a desperate need for novel and efficacious chemotherapeutic strategies for human brain cancers. There are abundant molecular alterations along the p53 and MDM2 pathways in human glioma, which play critical roles in drug resistance. The present study was designed to evaluate the in vitro and in vivo antitumor activity of a novel brain-penetrating small molecule MDM2 degrader, termed SP-141. In a panel of nine human glioblastoma and medulloblastoma cell lines, SP-141, as a single agent, potently killed the brain tumor-derived cell lines with IC 50 values ranging from 35.8 to 688.8 nM. Treatment with SP-141 resulted in diminished MDM2 and increased p53 and p21 cip1 levels, G2/M cell cycle arrest, and marked apoptosis. In intracranial xenograft models of U87MG glioblastoma (wt p53) and DAOY medulloblastoma (mutant p53) expressing luciferase, treatment with SP-141 caused a significant 4- to 9-fold decrease in tumor growth in the absence of discernible toxicity. Further, combination treatment with a low dose of SP-141 (IC 20 ) and temozolomide, a standard anti-glioma drug, led to synergistic cell killing (1.3- to 31-fold) in glioma cell lines, suggesting a novel means for overcoming temozolomide resistance. Considering that SP-141 can be taken up by the brain without the need for any special delivery, our results suggest that SP-141 should be further explored for the treatment of tumors of the central nervous system, regardless of the p53 status of the tumor.

The impact of diabetes mellitus on outcomes in trauma patients continues to attract interest, but data regarding the impact of longer term glycemic control are still lacking. This study evaluated the effect of long-term glycemic control on outcomes. Trauma patients presenting to the University of Alabama at Birmingham Hospital, between 2011 and 2018, were stratified into 4 groups, based on admission Hemoglobin A1c (HbA1c) level. A Poisson regression with robust error variance was used to estimate risk ratios and associated confidence intervals for the association between HbA1C and specific outcomes. A total of 26,134 patients were included. Patients without diabetes or excellent glycemic control (ND-EGC) had shorter hospital and ICU stay as well as fewer days on ventilator support. Compared with those with ND-EGC, the renal failure risk was higher for those with moderate (risk ratio [RR] 2.53, 95% confidence interval [CI] 1.76-3.63) and poor glycemic control (RR 3.20, 95% CI 2.18-4.71). Urinary tract infection risk was also higher for those with poor control (RR 1.83, 95% CI 1.17-2.02). Observed associations were of similar strength for pneumonia and mortality for all less-than-excellent glycemic control groups. In conclusion, trauma patients with worse long-term glycemic control had increased risks of developing pneumonia, renal failure, urinary tract infection, and death. HbA1c can prognosticate the risks and outcomes of diabetic trauma patients.

The tumor suppressor p53 is believed to be the mostly studied molecule in modern biomedical research. Although p53 interacts with hundreds of molecules to exert its biological functions, there are only a few modulators regulating its expression and function, with murine double minute 2 (MDM2) playing a key role in this regard. MDM2 also contributes to malignant transformation and cancer development through p53-dependent and -independent mechanisms. There is an increasing interest in developing MDM2 inhibitors for cancer prevention and therapy. We recently demonstrated that the nuclear factor of activated T cells 1 (NFAT1) activates MDM2 expression. NFAT1 regulates several cellular functions in cancer cells, such as cell proliferation, migration, invasion, angiogenesis, and drug resistance. Both NFAT isoforms and MDM2 are activated and overexpressed in several cancer subtypes. In addition, a positive correlation exists between NFAT1 and MDM2 in tumor tissues. Our recent clinical study has demonstrated that high expression levels of NFAT1 and MDM2 are independent predictors of a poor prognosis in patients with hepatocellular carcinoma. Thus, inhibition of the NFAT1-MDM2 pathway appears to be a novel potential therapeutic strategy for cancer. In this review, we summarize the potential oncogenic roles of MDM2 and NFAT1 in cancer cells and discuss the efforts of discovery and the development of several newly identified MDM2 and NFAT1 inhibitors, focusing on their potent in vitro and in vivo anticancer activities. This review also highlights strategies and future directions, including the need to focus on the development of more specific and effective NFAT1-MDM2 dual inhibitors for cancer therapy.

The murine double minute 2 (MDM2) oncogene exerts major oncogenic activities in human cancers; it is not only the best-documented negative regulator of the p53 tumor suppressor, but also exerts p53-independent activities. There is an increasing interest in developing MDM2-based targeted therapies. Several classes of MDM2 inhibitors have been evaluated in preclinical models, with a few entering clinical trials, mainly for cancer therapy. However, noncarcinogenic roles for MDM2 have also been identified, demonstrating that MDM2 is involved in many chronic diseases and conditions such as inflammation and autoimmune diseases, dementia and neurodegenerative diseases, heart failure and cardiovascular diseases, nephropathy, diabetes, obesity, and sterility. MDM2 inhibitors have been shown to have promising therapeutic efficacy for treating inflammation and other nonmalignant diseases in preclinical evaluations. Therefore, targeting MDM2 may represent a promising approach for treating and preventing these nonmalignant diseases. In addition, a better understanding of how MDM2 works in nonmalignant diseases may provide new biomarkers for their diagnosis, prognostic prediction, and monitoring of therapeutic outcome. In this review article, we pay special attention to the recent findings related to the roles of MDM2 in the pathogenesis of several nonmalignant diseases, the therapeutic potential of its downregulation or inhibition, and its use as a biomarker., (© 2019 Wiley Periodicals, Inc.)

Background: Preeclampsia (PE) is a serious complication of pregnancy and one of the main causes of maternal and neonatal mortality and morbidity in the world. Finding a biomarker with high sensitivity and specificity could lead to prediction and early diagnosis of the disease and reduces its complications. In this study, we evaluated diagnostic accuracy of Soluble fms-like tyrosine kinase-1 (sFlt-1) to Placental growth factor (PlGF) ratio for diagnosis of PE., Methods: The cases included 23 mild, 15 severe preeclamptic patients, and 20 normal term pregnant women as control referred to GYN ward of the Persian Gulf Hospital in Bandar Abbas from 2014 to 2016. Levels of sFlt-1 and PlGF were measured. Receiver Operating Characteristic (ROC) curve analysis was applied to calculate diagnostic accuracy of sFlt-1/PlGF ratio., Results: The mean Level of sFlt-1/PlGF in PE patients (91.33 ng/ml) was significantly higher than control women (17.62) (P<0.001). ROC curve analysis showed sFlt-1/PlGF ratio diagnostic accuracy in preeclamptic patients with Area Under Curve (AUC) of 0.90, the best cut-off value of 24.96, sensitivity and specificity of 84.2 and 85.0%, respectively., Conclusions: Our data showed sFlt-1/PlGF ratio has higher accuracy for differentiating PE patients from non-PEs in comparison with its power for differentiating severe or early onset forms of the disease.

[This corrects the article DOI: 10.1016/j.gendis.2019.06.001.]., (© 2019 Chongqing Medical University. Production and hosting by Elsevier B.V. All rights reserved.)

The development of hindlimbs in tetrapod species relies specifically on the transcription factor TBX4. In humans, heterozygous loss-of-function TBX4 mutations cause dominant small patella syndrome (SPS) due to haploinsufficiency. Here, we characterize a striking clinical entity in four fetuses with complete posterior amelia with pelvis and pulmonary hypoplasia (PAPPA). Through exome sequencing, we find that PAPPA syndrome is caused by homozygous TBX4 inactivating mutations during embryogenesis in humans. In two consanguineous couples, we uncover distinct germline TBX4 coding mutations, p.Tyr113 ∗ and p.Tyr127Asn, that segregated with SPS in heterozygous parents and with posterior amelia with pelvis and pulmonary hypoplasia syndrome (PAPPAS) in one available homozygous fetus. A complete absence of TBX4 transcripts in this proband with biallelic p.Tyr113 ∗ stop-gain mutations revealed nonsense-mediated decay of the endogenous mRNA. CRISPR/Cas9-mediated TBX4 deletion in Xenopus embryos confirmed its restricted role during leg development. We conclude that SPS and PAPPAS are allelic diseases of TBX4 deficiency and that TBX4 is an essential transcription factor for organogenesis of the lungs, pelvis, and hindlimbs in humans., (Copyright © 2019 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)

Acute myocardial infarction (AMI) is one of the leading causes of morbidity worldwide. Myocardial reperfusion is known as an effective therapeutic choice against AMI. However, reperfusion of blood flow induces ischemia/reperfusion (I/R) injury through different complex processes including ion accumulation, disruption of mitochondrial membrane potential, the formation of reactive oxygen species, and so forth. One of the processes that gets activated in response to I/R injury is autophagy. Indeed, autophagy acts as a "double-edged sword" in the pathology of myocardial I/R injury and there is a controversy about autophagy being beneficial or detrimental. On the basis of the autophagy effect and regulation on myocardial I/R injury, many studies targeted it as a therapeutic strategy. In this review, we discuss the role of autophagy in I/R injury and its targeting as a therapeutic strategy., (© 2019 Wiley Periodicals, Inc.)

Overexpression of the MDM2 oncogene and mutations in the p53 tumor suppressor commonly occur in hepatocellular carcinoma (HCC) and are associated with increased mortality due to this disease. Inhibiting MDM2 has been demonstrated to be a valid approach for the treatment of HCC. However, most of the MDM2 inhibitors evaluated to date have been designed to block the MDM2 and p53 binding, and have limited efficacy against tumors with mutant or deficient p53. In the present study, we developed a novel MDM2 inhibitor (termed SP141) that has direct effects on MDM2 and exerts anti-HCC activity independent of the p53 status of the cancer cells. We demonstrate that SP141 inhibits cell growth and prevents cell migration and invasion, independent of p53. Mechanistically, SP141 directly binds the MDM2 protein and promotes MDM2 degradation. The inhibition of MDM2 by SP141 also increases the sensitivity of HCC cells to sorafenib. In addition, in orthotopic and patient-derived xenograft models, SP141 inhibits MDM2 expression and suppresses tumor growth and metastasis, without any host toxicity. Furthermore, the inhibition of MDM2 by SP141 is essential for its anti-HCC activities. These results provide support for the further development of SP141 as a lead candidate for the treatment of HCC., (© 2019 Chongqing Medical University. Production and hosting by Elsevier B.V.)

Background: Postoperative cognitive decline is a common complication observed frequently after general anesthesia in the immediate postoperative phase. We studied the effects of dexmedetomidine versus midazolam during coronary artery bypass graft (CABG) surgery on cognitive and memory function. Methods: In this clinical trial, 42 elective on-pump CABG candidates under general anesthesia, aged between 40 and 65 years, were enrolled randomly in 2 groups. Group A received 0.05-0.1 mg/kg of midazolam and Group B received 1 µg/kg of dexmedetomidine. One day before surgery, all the participants underwent the Persian version of the Mini-Mental State Examination (MMSE) and the Persian version of the Wechsler Memory Scale (WMS) test for a comparison of cognitive impairment and memory functions. Both groups were given fentanyl and propofol for the induction of anesthesia and muscle relaxants. The MMSE and WMS tests were repeated 5 and 30 days after surgery. Results: The mean±SD of age was 55.47±7.18 y in Group A and 55.39±6.08 y in Group B. Eighty percent of the participants were men in both groups. There were no significant differences between Group A and Group B in the MMSE and WMS before surgery (89.04±14.30 vs. 97.10±18.10, respectively; P=0.059), but the WMS was significantly different 30 days after surgery (87.60±14.30 vs. 103.53±19.93, respectively; P=0.005). Group A showed high cognitive impairment and low WMS scores compared with Group B (P=0.005). Additionally, the MMSE results were not statistically different between the 2 groups postoperatively (24.80±3.18 vs. 23.55±4.18, respectively; P=0.394). Conclusion: Our results showed that dexmedetomidine might have a lower impact on cognitive function than might midazolam among patients undergoing CABG., (Copyright © 2015 Tehran Heart Center, Tehran University of Medical Sciences.)

Problem: The steep increase and inappropriateness of caesarean birth represent a healthcare problem in Iran., Aim: The purpose of study was to evaluate the effect of a campaign based on social marketing to promote normal childbirth., Method: The study was designed as a prospective case control study. The social marketing campaign was implemented from March 2016 to January 2017. A demographic data questionnaire, obstetrical history questionnaire, maternal knowledge assessment questionnaire, and maternal health belief questionnaire comprised the instruments for this study. Only women planning a caesarean birth without any medical indications for the caesarean were enrolled in the study as a case. Those who met the same inclusion criteria and did not want to participate in the campaign were assigned to the control group., Findings: In total, 350 first-time pregnant women who composed the campaign group (n=194) and control group (n=156) completed the study. The mean baseline level of knowledge and Health Belief Model component score did not differ between the two groups at baseline. However, after the campaign, knowledge scores, perceived severity, perceived susceptibility, self-efficacy, and cues to action scores differed significantly between the campaign and control groups. The follow-up of all participants in both groups showed that 35.6% (n=69) of participants in the campaign group chose natural birth as their birth method, whereas only 13.5% (n=21) in the control group delivered their newborn vaginally., Conclusion: The B Butterfly social marketing campaign successfully targeted first-time pregnant women who chose to have unnecessary elective cesarean births., (Copyright © 2018 Australian College of Midwives. Published by Elsevier Ltd. All rights reserved.)

Despite recent advances in the treatment of cardiac arrhythmia, the available options are still limited and associated with some complications. Induction of biological pacemakers via Tbx18 gene insertion in the heart tissue has been suggested as a promising therapeutic strategy for cardiac arrhythmia. Following a previous in vitro study reporting the production of Tbx18-expressing human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs), we aimed to investigate the efficacy of these engineered cells to generate pacemaker rhythms in a murine model of complete heart block. We also attempted to generate a functional pacemaker by Tbx18 overexpression in native cardiac cells of rat heart. The hiPSC-derived pacemaker cells were produced by lentiviral delivery of Tbx18 gene to stem cells during a small molecule-based differentiation process. In the present study, 16 male albino Wistar rats were randomly assigned to Tbx18-lentivirus (n = 4) and Tbx18-pacemaker cells (n = 4) administered via injection into the left ventricular anterolateral wall. The control rats received GFP-lentiviruses (n = 4) and GFP-pacemaker cells (n = 4). Fourteen days after the injection, the rats were sacrificed and analyzed by electrocardiography (ECG) recording using a Langendorff-perfused heart model following complete heart block induced by hypokalemia and crashing. Immunofluorescence staining was used to investigate the expression of Tbx18, HCN4 and connexin 43 (Cx43) proteins in Tbx18-delivered cells of heart tissues. The heart rate was significantly reduced after complete heart block in all of the experimental rats (P < 0.05). Heart beating in the Tbx18-transduced hearts was slower compared with rats receiving Tbx18-pacemaker cells (P = 0.04). The duration of ventricular fibrillation (VF) was higher in the lentiviral Tbx18 group compared with the GFP-injected controls (P = 0.02) and the Tbx18-pacemaker cell group (P = 0.02). The ECG recording data showed spontaneous pacemaker rhythms in both intervention groups with signal propagation in Tbx18-transduced ventricles. Immunostaining results confirmed the overexpression of HCN4 and downregulation of Cx43 as a result of the expression of the Tbx18 gene and spontaneously contracting myocyte formation. We confirmed the formation of a functional pacemaker after introduction of Tbx18 via cell and gene therapy strategies. Although the pacemaker activity was better in gene-received hearts since there were longer VF duration and signal propagation from the injection site, more data should be gathered from the long-term activity of such pacemakers in different hosts., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Oxytocin (OT) has a postconditioning effect against the ischemia-reperfusion (I/R) injury. However, its precise cardioprotection mechanism at the early reperfusion phase remains under debate. Our previous study revealed that OT postconditioning (OTpost) is cardioprotective by activating the Reperfusion Injury Salvage Kinase (RISK) pathway. Therefore, the present study is aimed to determine the biological effects of OTpost via the OT receptor and the activation of the JAK/STAT3 signaling pathway, mitochondrial adenosine triphosphate-dependent potassium channel (mitoKATP), nitric oxide (NO) release, and its anti-apoptotic effects against I/R injury in an isolated rat heart model. Sixty-three rats were randomly allocated to one of nine groups. OT was perfused 40 min prior to the regional ischemia or 15 min at the early reperfusion phase. AG490 (a JAK/STAT3 inhibitor), 5HD (a mitoKATP blocker), atosiban (an OT receptor antagonist), L-NAME (a nonspecific nitric oxide synthase inhibitor) were applied either alone or in combination with OT during the pre-ischemia phase and/or in the early reperfusion phase. Myocardial infarct size, hemodynamic factor, ventricular arrhythmia, coronary flow, cardiac biochemical marker, and the apoptosis index were determined at the end of reperfusion. Oxytocin postconditioning reduced infarct size, lactate dehydrogenase activity, arrhythmia score, ventricular fibrillation, and apoptosis. Moreover, AG490, 5HD, atosiban, and L-NAME abrogated the cardioprotective effects of OT. Our results demonstrated that the cardioprotective effects of OT are mediated by NO release, and the activation of mitoKATP and the SAFE pathway through the JAK/STAT3 signaling cascade that finally lead to decrease in the apoptosis index during the early reperfusion phase., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Recent work has shown that optical magnetism, generally considered a challenging light-matter interaction, can be significant at the nanoscale. In particular, the dielectric nanostructures that support magnetic Mie resonances are low-loss and versatile optical magnetic elements that can effectively manipulate the magnetic field of light. However, the narrow magnetic resonance band of dielectric Mie resonators is often overshadowed by the electric response, which prohibits the use of such nanoresonators as efficient magnetic nanoantennas. Here, we design and fabricate a silicon (Si) truncated cone magnetic Mie resonator at visible frequencies and excite the magnetic mode exclusively by a tightly focused azimuthally polarized beam. We use photoinduced force microscopy to experimentally characterize the local electric near-field distribution in the immediate vicinity of the Si truncated cone at the nanoscale and then create an analytical model of such structure that exhibits a matching electric field distribution. We use this model to interpret the PiFM measurement that visualizes the electric near-field profile of the Si truncated cone with a superior signal-to-noise ratio and infer the magnetic response of the Si truncated cone at the beam singularity. Finally, we perform a multipole analysis to quantitatively present the dominance of the magnetic dipole moment contribution compared to other multipole contributions into the total scattered power of the proposed structure. This work demonstrates the excellent efficiency and simplicity of our method of using Si truncated cone structure under APB illumination compared to other approaches to achieve dominant magnetic excitations.

Background: Previous studies have shown that proanthocyanidins have cardioprotective effects which are mediated via the release of nitric oxide (NO) ultimately resulting in increasing the antioxidant activity. We have investigated to show whether 1) the total extract and ethyl acetate fraction (Et) of Potentilla reptans root have an ischemic preconditioning (IPC) effect, 2) P. reptans has antioxidant and cardioprotective effects mediated by nuclear factor erythroid 2-related factor 2 (Nrf2) pathway and scavenging of reactive oxygen species (ROS), 3) NO, caspase-3 and Bcl-2/Bax are involved in the IPC effect of P. reptans., Methods: Male Wistar rats were divided into 10 groups. The isolated hearts were subjected to 30 min of ischemia and 100 min of reperfusion. The P. reptans was applied before the main ischemia. The infarct size was estimated by triphenyl-tetrazolium chloride staining. The hemodynamic parameters and ventricular arrhythmias were calculated during the reperfusion. Antioxidant markers and immunohistochemistry assays were determined at the end of the protocol., Results: The Et significantly decreased the infarct size, arrhythmia scores, ventricular fibrillation incidence, and enhanced the hemodynamic parameters in a concentration-dependent manner against the ischemia/reperfusion group. SOD and CAT activity were increased and MDA level was decreased in response to the Et. Meanwhile, Et attenuated the suppression of Nrf2 expression and reduced the apoptotic indexes. The cardioprotective effect of P. reptans was abrogated by L-NAME., Conclusions: P. reptans demonstrated that the cardioprotective preconditioning effects via NO release, Nrf2 pathway, and antioxidant activity lead to a decrease in the apoptotic index., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: In spite of medical indications, preferences for the mode of delivery are influenced by several factors. However, as the literature suggests, the underlying motivation of women choosing vaginal delivery is rarely attended to. The current study aimed to explore first-time pregnant women's motivation for planning vaginal delivery., Materials and Methods: An exploratory design with in-depth interviews was employed from September 2015 to March 2016. Participants were asked key questions about their beliefs about vaginal delivery, perceived outcomes of vaginal delivery, the impact of others perspectives on their decision, and factors that might inhibit or facilitate vaginal delivery. A community advertisement was placed in obstetricians' offices, public health departments, as well as beauty salons throughout the city of Bandar Abbas, Iran, to enroll target participants. All interviews were tape-recorded, transcribed, and subsequently analyzed., Results: Twelve pregnant women within the age range of 19-33 years volunteered to participate. Ninety four initial codes were obtained. These codes were then summed up into three themes as well as six subthemes. The three themes specified were personal beliefs, deliberation and risk assessment, and personal autonomy., Conclusions: A number of key motivating factors such as fast recovery after vaginal delivery, immediate breastfeeding, and powerful bonding were identified, which were influential in choosing vaginal delivery. Awareness of the fact that the provided information shapes women's beliefs and can lead to attitude changes, midwives played a key role in shaping positive and healthy attitudes toward natural birth giving as well as empower them to make autonomous decision., Competing Interests: Nothing to declare.

We propose using a Si tip-Au nanoparticle (NP) combination system in photoinduced force microscopy (PiFM) to fundamentally improve its accuracy in the nanoscale characterization of light-matter interaction. Compared to conventional PiFM with Au-coated tips, such Si tip and Au NP combination enables superior photo-induced force detection while overcoming the tip-induced anisotropy by Au-coating. We map the near-field distribution of Au NPs in different arrangements achieving 120 signal-to-noise ratio and sub-6-nm resolution, even surpassing the tip-curvature limitation; we also map the azimuthally polarized beam profile showing an excellent symmetry. The proposed approach is essential to the promising single molecule spectroscopy.

Background: The use of biomarkers for diagnosis of Preeclampsia (PE), a life-threatening pregnancy disorder, could reduce serious complications of this disease. In this study, we investigated dysregulation of endoglin (Eng) expression and diagnostic accuracy of soluble endoglin (sEng) in PE patients., Methods: For this case-control study, 26 mild and 15 severe preeclamptic women along with 20 normotensive controls were recruited. The expression level of Eng (the co-receptor of TGF-β1) was evaluated using qRT-PCR. Also, the serum concentration of soluble Eng and expression of membranous Eng were determined by ELISA and immunohistochemistry., Results: A significant up-regulation in Eng mRNA and sEng levels was observed in PE patients versus normal controls. Immunohistochemistry (IHC) showed up-regulation of membranous Eng staining in syncytiotrophoblast and cytotrophoblast cells of PE patients. The serum levels of sEng were significantly increased in all patients (mild, sever, early- and late-onset) as compared to healthy pregnant women (P˂0.001). Receiver-operating characteristic (ROC) curve analysis revealed that sEng had the highest accuracy in distinguishing PE from normal pregnancies with cut-off value of 20.4, sensitivity of 92.1%, specificity of 90%, and area under the curve (AUC) of 0.94 (95% CI: 0.88-1.00)., Conclusion: Our data showed that the up-regulation of Eng mRNA along with its membranous and soluble form in PE patients leads to defect in angiogenesis pathway. Also, the results of this study revealed sEng potential as a marker for diagnosis of PE and its severity.

The phenomenon of caesarean birth on demand has gained attention, particularly as a first caesarean birth appears to be strongly predictive of subsequent caesareans. Identification of reasons behind caesarean birth on demand is important for planning effective interventions. Therefore, this review reports the factors involved in the tendency of women to undergo caesarean birth, based on studies in the Islamic Republic of Iran. Several keywords including caesarean delivery, childbirth, causes, maternal request/demand, and patient choice were used to search Medline, PubMed, Ovid, Scientific Information Database, Magiran, Google and Google Scholar. The search was conducted on Persian and English language articles, with no time limitation. Using content analysis, the factors influencing caesarean section were divided into 3 categories: maternal, social and healthcare giver. According to the high prevalence of caesarean section, it is important to design and implement effective programmes and interventions with consideration of the key reasons that lead women to opt for unnecessary caesarean section.

Background: Preeclampsia (PE) is a serious complication of pregnancy with hallmarks of incomplete placentation, placental ischemia and endothelial dysfunction. Imbalance between vascular endothelial growth factor (VEGF), placenta growth factor (PlGF) and their receptors play important role in pathophysiology of PE., Objective: This study was aimed to asses PlGF mRNA expression in placenta of women affected with PE., Material and Methods: In this cross-sectional study, expression of PlGF mRNA was evaluated in 26 mild PE cases, 15 severe preeclamptic women and 20 normotensive controls. Patients were sub-classified as early onset PE (9) and late onset (32). After RNA extraction, PlGF expression was quantified with qRT-PCR., Results: The results of PlGF mRNA expression between mild-severe, and early-late onset PE patients showed no statistically significant difference compared with the control group (p=0.661, p=0.205 respectively)., Conclusion: Despite we found no distinct differential expression of PlGF mRNA in placental tissue of PE patients compared with control women, but according to decreased level of this angiogenic factor in PE even before clinical onset of the disease, determining molecular mechanisms related to reduced secretion of PlGF into the maternal circulation may be useful for future therapeutics., Competing Interests: The authors report no conflicts of interest.

Background: Although vaginal birth is the safest type of childbirth, sometimes caesarean is necessary for the safety of the mother or the infant. The problem is that low-risk, healthy women are choosing caesarean as a birth option despite the fact that it is fraught with possible complications., Aim: To determine the differences and identify the predictors for the way women plan their childbirth based on Health Belief Model., Methods: A cross-sectional study was conducted in Bandar abbas city, Iran, from May to October 2015. The study recruited eligible women who self identified themselves as requesting a caesarean or vaginal birth in their response to a questionnaire., Findings: Of 470 recruited women, 183 (38.9%) planned to have a caesarean without medical indication. Maternal characteristics (age, level of education, occupational status, involvement in a medical profession, and household income) and obstetric variables (health provider type, place of prenatal care, and the number of children planned for the future) influenced the decisions made by the women. There was a significant difference between women planning a caesarean and those planning vaginal birth in terms of childbirth knowledge. Significant differences were observed regarding maternal self-efficacy, with women planning a caesarean reporting significantly lower self-efficacy than women planning a vaginal birth. Women planning a caesarean birth were also significantly less likely to perceive themselves as being at risk for caesarean-related side effects than women planning a vaginal birth., Conclusion: Comprehensive childbirth knowledge can lead to positive maternal attitude towards vaginal birth and may improve birth confidence., (Copyright © 2016 Australian College of Midwives. Published by Elsevier Ltd. All rights reserved.)

Aim: The purpose of this study was to determine threshold gamma probe counts to distinguish single adenoma (SA) from multigland disease (MGD) during radioguided parathyroidectomy., Methods: A retrospective analysis of 1656 patients was performed. Ex vivo counts of the first excised gland were taken and recorded as a percentage of background counts., Results: 69.4% of MGD patients had counts below the 50% threshold. The 50% threshold correctly grouped 72.8% of our cohort. Counts of more than 100% were accurate for grouping SA, with only 6.8% of patients with counts more than 100% having MGD., Conclusions: The gamma probe can aid surgeons in deciding to continue neck exploration if MGD is suspected or wait for labs to confirm cure if SA is suspected.