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Opium use is one of the most common forms of substance abuse in Iran and there are some evidence indicating it is a risk factor of transitional cell carcinoma (TCC) of the urinary bladder. The majority of opium users are also cigarette smokers, so consideration of the high prevalence of smoking which is the most important risk factor of TCC of the urinary bladder among opium users is essential to assess the role of opium use as a possible risk factor of TCC. This study was done to evaluate the role of opium as a risk factor of TCC. A case-control study was performed on 255 individuals diagnosed with TCC of the urinary bladder by pathologic light microscopic examination of the tumor biopsies. Control population was chosen from individuals who had no history or presenting signs or symptoms of urinary problems. Case and control groups were matched by sex and age and also by cigarette smoking habits. Forty-one (18.1%) of the cases and 12 (5%) of controls were recognized to be opium users. Mantel-Haenszel analysis showed an odds ratio of 3.88, with 95% confidence interval of 1.99-7.57 and P value of < 0.001. Results indicate that opium use is a risk factor for TCC. The majority of opium users are also cigarette smokers, which is another important risk factor for TCC. Routine urine cytology and early evaluation in the patients presenting with any of the symptoms of urinary bladder malignancy by means of cystoscopy and urine cytology are highly recommended.

One of the complications of end-stage renal disease (ESRD) is sensorineural hearing loss (SNHL). Despite large number of studies on adults ESRD patients, there are only a few reported surveys regarding SNHL in children. To determine the prevalence of SNHL in children with ESRD and its relationship with sex of patients, presence of hypertension, history of ototoxic drugs administration and duration of dialysis, we evaluated 30 children and adolescents suffering from ESRD who were under hemodialysis therapy with standard pure-tone audiometry. The ages of children were 5-17.5 years (mean 12 years). Patients with Alport’s syndrome and other hereditary or congenital syndromes involving the ears were excluded from the study. SNHL was detected in 9 patients (30%); 3 children had unilateral and 6 had bilateral SNHL (15 ears). In all of these 15 ears SNHL was in high frequencies (4000-8000 Hz). In 10 ears (66%) also there was SNHL in middle frequencies and in 7 ears (46.6%)there was hearing loss in all frequencies (250-8000 Hz). The severity of SNHL was mild in 7, moderate in 9, severe in 13 and profound in 3 ears in at least one frequency. There was no significant relationship between SNHL and sex of patients, presence of hypertension, history of ototoxic drugs administration and duration of dialysis (P values were 0.8107, 0.3217, 0.69, 0.087, respectively). SNHL is common in children and adolescents with ESRD and must be considered in rehabilitation of these children; the etiology of this impairment is not clear.

Background: In‐depth insight into haemodynamic changes during normotensive pregnancy may help identify women at risk for gestational hypertensive complications. Objectives: To determine the magnitude of changes in cardiac output and its determinants stroke volume and heart rate, and total peripheral vascular resistance during singleton normotensive and hypertensive pregnancies. Search strategy: PubMed (NCBI) and Embase (Ovid) databases were searched from their inception up to November 2019. Selection criteria: Studies reporting original measurements of haemodynamic parameters during pregnancy together with a non‐pregnant reference measurement. Studies including women using antihypertensive medication were excluded. Data collection and analysis: Pooled mean differences between pregnant and non‐pregnant women, and absolute values of haemodynamic parameters were calculated for predefined gestational intervals using a random‐effects model in normotensive and hypertensive pregnancy. Meta‐regression analysis was used to analyse group differences in adjustments and absolute values during pregnancy. Main results: In normotensive pregnancies, cardiac output increased from the first weeks on, reaching its highest level early in the third trimester (mean difference, 1.41 l·min1; 95% CI 1.18–1.63 l·min). In parallel, vascular resistance decreased progressively until its nadir in the early third trimester (mean difference, −331 dyn·sec–1·cm–5; 95% CI −384 to −277 dyn·sec–1·cm–5) and then increased slightly at term. In hypertensive pregnancies, the initial cardiac output increase was higher and vascular resistance did not change throughout gestation compared with reference values. Conclusions: Hemodynamic changes in women who eventually develop hypertensive complications are substantially different. Serial monitoring and plotting against developed normograms can identify women at risk and may allow timely intervention. Monitoring haemodynamic changes in pregnancy helps identify women at risk for hypertensive complications. Monitoring haemodynamic changes in pregnancy helps identify women at risk for hypertensive complications. [ABSTRACT FROM AUTHOR]

Sugar-sweetened beverage (SSB) consumption remains a major target for interventions to treat severe obesity in children. Understanding how total energy consumption is divided among different types of beverages remains unclear. This study retrospectively examined how the consumption of beverage calories (kcal) from 100% fruit juice and SSBs, and body mass index, assessed as a percent of the 95th sex- and age-specific percentile (%of 95BMI), changed during the treatment of children with obesity aged 2-18 years. Treatment was provided by an integrative multi-disciplinary team, comprising a physician, a dietician/ nutritionist and a behavioralist employing motivational interviewing and a small change approach to promote improved sustainable health habits and induce a net negative energy balance. The sample included 155 patients, with 341 visits. The median age was 11 years, 60% were girls, and there was a median follow-up of 3.1 months. At baseline, the median %of 95BMI was 135 and the median kcal/day intake was 436 from juice and 263 from SSB. For each additional 100 kcal consumed/day from SSB and juice, the %of 95BMI increased by 1.4 percentage points. In the follow-up, each additional month was associated with 7 fewer kcal/day from SSB and juice combined, with a 0.5 percentage point increase in %of 95BMI. Children in this treatment program consumed fewer calories from SSB over time, although the %of 95BMI did not decrease. SSBs other than soda accounted for the majority of beverage kcal intake, therefore potentially providing a targeted direction for interventions.

Background: Although speech and voice disorders are common in Parkinson's disease (PD), there is insufficient evidence to support the effectiveness of behavioural speech therapies in these patients., Aims: This study aimed to examine the effects of a new tele-rehabilitation program, a combining of conventional speech therapy and singing intervention, on voice deficits in patients with PD., Methods & Procedures: This study was a three-armed, assessor-masked, randomised controlled trial. Thirty-three people with PD were randomly assigned to the combination therapy, conventional speech therapy, or singing intervention group. This study followed the Consolidated Standards of Reporting Trials guidelines for non-pharmacological treatment. Each patient participated in 12 tele-rehabilitation sessions over 4 weeks. The combination therapy group received speech and singing interventions simultaneously (respiratory, speech, voice, and singing exercises). Voice intensity as a primary outcome and the voice handicap index (VHI), maximum frequency range, jitter and shimmer as secondary outcomes were evaluated 1 week before the first intervention session, 1 week after the last intervention session and 3 months after the last evaluation., Outcomes & Results: The results of repeated measures analysis of variance showed a significant main effect of time on all outcomes in all three groups after treatment (p < 0.001). There was a significant group effect for voice intensity (p < 0.001), VHI (p < 0.001), maximum frequency range (p = 0.014) and shimmer (p = 0.001). The combination therapy group demonstrated a significant outperformance in the VHI and shimmer than the speech therapy (p = 0.038) and singing intervention (p < 0.001) groups. The results of this study also indicated that combination therapy group compared to singing intervention group had a larger effect on voice intensity (p < 0.001), shimmer (p < 0.001) and maximum frequency range (p = 0.048)., Conclusions & Implication: The results demonstrated that combining speech therapy with a singing intervention delivered through tele-rehabilitation might be more effective in improving voice problems in patients with PD., What This Paper Adds: What is already known on the subject Parkinson's disease (PD) is a neurological disorder that frequently causes disturbances in speech and voice, which negatively affect patients' quality of life. Although speech difficulties occur in 90% of patients with PD, evidence-based treatment options for speech and language problems in these patients are limited. Therefore, further studies are required to develop and assess evidence-based treatment programs. What this study adds The findings of this study showed that a combination therapy program including conventional speech therapy approaches and individual singing intervention provided through tele-rehabilitation may have a greater effect on the improvement of voice problems in people with PD compared to speech therapy and singing intervention alone. What are the clinical implications of this work? Tele-rehabilitation combination therapy is an inexpensive and enjoyable behavioural treatment. The advantages of this method are that it is easy to access, appropriate for many stages of voice problems in PD, requires no prior singing training, encourages voice health and self-management and maximises treatment resources available to people with PD. We believe that the results of this study can provide a new clinical basis for treatment of voice disorders in people with PD., (© 2023 Royal College of Speech and Language Therapists.)

The current study aimed to determine the community-based COVID-19 prevalence and compare the symptom-based and test-based prevalence rates in the Omicron peak (February 20 to March 20, 2022) to assess community involvement and provide effective healthcare. This cross-sectional and population-based study examined the prevalence of COVID-19 from February 20 to March 20, 2022, in the city of Khomein in Markazi Province (located in central Iran) through random cluster sampling. The period prevalence of recurrent Omicron symptoms was 37.69%. Factors such as residence in urban areas (OR = 1.25, 95% CI: 0.95-1.66), number of COVID-19 vaccine doses (OR = 0.80, 95% CI: 0.67-0.95), the interval of last vaccination dose (OR = 1.04, 95% CI: 0.97-1.11) and a history of COVID-19 (OR =1.20, 95% CI: 1.04-1.39) were among the most important risk factors for Omicron. Ongoing efforts to vaccinate high-risk populations as well as stronger actions to diminish the Omicron consequences are fundamental obligations of the health system., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Journal of Education and Health Promotion.)

School closures during the COVID-19 pandemic have been reported to influence adolescents' behavioral health and may have altered their exposure to injury risk. We aimed to determine how in-person school attendance of individual adolescents in the United States during the pandemic was correlated with a range of risky health behaviors. We used self-reported data from adolescents 14-18 years old enrolled in grades 9-12 who participated in the 2020 Adolescent Behaviors and Experiences Survey. The exposure of interest was in-person vs remote school attendance in the previous 30 days. Risk behavior outcomes included not wearing a seatbelt when riding in a car; riding with someone who was drinking and driving; suffering intimate partner violence (IPV); forced sexual encounters; suicidal ideation; suicidal planning; electronic bullying; gun carrying; and physical fighting. Based on a multivariable analysis of 5202 students (65% attending school in-person) adjusted for age, sex, race, ethnicity, sexual orientation, parental unemployment, food insecurity, and homelessness, we found that in-person school attendance was associated with increased odds of every risk behavior except suicidal ideation and electronic bullying, with adjusted odds ratios ranging from 1.40 (95% confidence interval [CI]: 1.04, 1.88) for not wearing a seatbelt to 3.43 for IPV (95% CI: 1.97, 5.97). Our analyses demonstrate that in-person school attendance during the COVID-19 pandemic was associated with higher rates of risk behavior among adolescents. Further research is needed explore if this relationship is causal, and how these risks could be mitigated, as most adolescents have now returned to in-person schooling., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: In-depth insight into haemodynamic changes during normotensive pregnancy may help identify women at risk for gestational hypertensive complications., Objectives: To determine the magnitude of changes in cardiac output and its determinants stroke volume and heart rate, and total peripheral vascular resistance during singleton normotensive and hypertensive pregnancies., Search Strategy: PubMed (NCBI) and Embase (Ovid) databases were searched from their inception up to November 2019., Selection Criteria: Studies reporting original measurements of haemodynamic parameters during pregnancy together with a non-pregnant reference measurement. Studies including women using antihypertensive medication were excluded., Data Collection and Analysis: Pooled mean differences between pregnant and non-pregnant women, and absolute values of haemodynamic parameters were calculated for predefined gestational intervals using a random-effects model in normotensive and hypertensive pregnancy. Meta-regression analysis was used to analyse group differences in adjustments and absolute values during pregnancy., Main Results: In normotensive pregnancies, cardiac output increased from the first weeks on, reaching its highest level early in the third trimester (mean difference, 1.41 l·min 1 ; 95% CI 1.18-1.63 l·min). In parallel, vascular resistance decreased progressively until its nadir in the early third trimester (mean difference, -331 dyn·sec -1 ·cm -5 ; 95% CI -384 to -277 dyn·sec -1 ·cm -5 ) and then increased slightly at term. In hypertensive pregnancies, the initial cardiac output increase was higher and vascular resistance did not change throughout gestation compared with reference values., Conclusions: Hemodynamic changes in women who eventually develop hypertensive complications are substantially different. Serial monitoring and plotting against developed normograms can identify women at risk and may allow timely intervention., Tweetable Abstract: Monitoring haemodynamic changes in pregnancy helps identify women at risk for hypertensive complications., (© 2021 The Authors. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd.)

Gestational hypertensive complications are preceded by deviant hemodynamic adjustments affecting blood pressure. Our objective was to determine the timing and magnitude of changes in blood pressure during singleton normotensive and hypertensive pregnancies. PubMed (NCBI) and Embase (Ovid) databases were searched for relevant studies up to November 2019. Studies reporting original blood pressure measurements during pregnancy together with a non-pregnant reference measurement were included. Studies including women with a history of cardiovascular or metabolic disease, or women using antihypertensive drugs were excluded. Pooled mean differences between pregnant and non-pregnant women, and absolute blood pressure values were calculated for predefined gestational intervals in normotensive and hypertensive pregnancy, using a random-effects model. Meta-regression analysis was used to analyze group differences in adjustments. In early normotensive pregnancy, both systolic and diastolic blood pressure decreased, reaching their maximum reduction of -4 mmHg (95%CI -6 to -1 mmHg) and -4 mmHg (95%CI, -5 to -3 mmHg), respectively in the second trimester. Thereafter, blood pressure gradually increased towards non-pregnant values. All absolute blood pressure measurements throughout normotensive pregnancy were below 130/80 mmHg. In hypertensive pregnancies, only diastolic blood pressure decreased early in pregnancy. In conclusion, this meta-analysis showed a clinically moderate, but significant mid-pregnancy drop in blood pressure during normotensive pregnancy. Reference curves with absolute values underscore the current liberal cut-off limit for gestational hypertension. A lack of a mid-pregnancy systolic blood pressure drop might reflect increased vascular resistance in women destined to develop hypertensive pregnancy complications., (Copyright © 2021. Published by Elsevier B.V.)

Objectives: Excessive left ventricular mass (LVM) results in inefficient LV work with energy waste leading to a negative prognostic effect. We aimed at investigating the presence of inappropriate LVM and calculating the myocardial mechano-energetic efficiency index (MEEi) in former pre-eclamptic (PE) women (with or without HELLP syndrome) compared to women who experienced HELLP syndrome without PE., Study Design: In this cross-sectional study, women with a history of normotensive HELLP (n = 32), PE without HELLP (n = 59), and PE with HELLP (n = 101) underwent echocardiography as part of the clinical CV work-up after their complicated pregnancies from 6 months to 4 years postpartum. We excluded women with comorbidities, including chronic hypertension, hypercholesterolemia, and obesity., Main Outcome Measures: LVM excess was calculated as the ratio between observed LVM and predicted LVM (by sex, stroke work and height), while MEEi was considered as the ratio between stroke work and "double product" (to approximate energy consumption), indexed to LVM., Results: LV hypertrophy was present in 8-14% and concentric remodeling in 31-42% of women, without intergroup difference. LVM was inappropriate in one-third of normotensive former HELLP and in about one-half of PE with or without HELLP, with no difference among groups. Accordingly, without nominal difference, MEEi showed a tendency towards lower values in former pre-eclamptic individuals., Conclusions: Women with a history of HELLP syndrome, independently from the presence/absence of PE, showed inappropriate LVM in the first 4 years after delivery, which may partially explain the elevated CV risk in these women compared to the general female population., (Copyright © 2021 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.)

Objectives: Pregnancy complicated by pre-eclampsia (PE) and hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome is associated with an increased risk of cardiovascular (CV) diseases later in life. Subclinical cardiac alterations precede eminent CV diseases. Speckle-tracking echocardiography (STE) is an effective method to assess subclinical myocardial dysfunction. We performed a myocardial speckle tracking study to investigate the prevalence of subclinical myocardial dysfunction in former PE patients (with and without HELLP syndrome) compared to normotensive women affected by HELLP syndrome., Methods: In this cross-sectional retrospective study, women with a history of normotensive HELLP (n = 32), PE without HELLP (n = 59), and PE with HELLP (n = 101) underwent conventional and STE as part of the clinical CV work-up after their complicated pregnancies from 6 months to 4 years postpartum. We excluded women with comorbidities, including chronic hypertension, hypercholesterolemia, and obesity., Results: Women with a history of PE with HELLP syndrome were characterized by a higher prevalence of altered left ventricular circumferential and global longitudinal two-dimensional (2D) strain (74 and 20%, respectively), altered right ventricular longitudinal 2D strain (37%), and left atrial (LA) 2D strain (57%). Moreover, a higher proportion of alterations of biventricular and LA strains was also present in former PE without HELLP as well as in the normotensive HELLP group., Conclusions: In the first years after a pregnancy complicated by HELLP syndrome, irrespective of whether there was concomitant PE, a higher rate of abnormal STE myocardial function is observed. Therefore, these women may benefit from CV risk management., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To meta-analytically determine the adaptation of left ventricular diastolic function (LVDF)-indices to singleton normotensive pregnancies., Methods: Literature was retrieved from PubMed and Embase. We included studies that reported a nonpregnant reference measurement and LVDF indices (mitral inflow signals, left atrial volume and tissue Doppler measurements). Mean differences between pregnant and reference measurements and weighted means of absolute values were calculated using a random-effects model., Results: We included 34 eligible studies. Normotensive pregnancies were characterized by an initially larger increase in the passive left ventricular filling (E-wave peak velocity, 13%) compared to active left ventricular filling during diastole (A-wave peak velocity, 6%) resulting in a 16% increase of the E/A ratio in the first trimester. The E/A ratio progressively decreased during advancing gestation to -18% at term, resulting from stabilizing E-wave peak velocity and increased A-wave peak velocity. The E/e' ratio was increased between 22 and 35 weeks (a maximal increase of 13%) in normotensive pregnancy. Left atrial volume (LAV) progressively increased from 15 weeks onwards with a maximal increase of 30% between 36 and 41 weeks., Conclusion: LVDF in normotensive pregnancy was improved in the first trimester after which LVDF progressively worsened. Large-scale studies in normotensive and hypertensive complicated pregnancies are needed for a more precise insight into LVDF changes during pregnancy., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.)

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetic cardiac disease characterized by progressive myocardial fibro-fatty replacement, arrhythmias and risk of sudden death. Its diagnosis is challenging and often it is achieved after disease onset or postmortem. In this study, we sought to identify circulating microRNAs (miRNAs) differentially expressed in ARVC patients compared to healthy controls. In the pilot study, we screened the expression of 754 miRNAs from 21 ARVC patients and 20 healthy controls. After filtering the miRNAs considering a log fold-change cut-off of ±1, p -value < 0.05, we selected five candidate miRNAs for a subsequent validation study in which we used TaqMan-based real-time PCR to analyse samples from 37 ARVC patients and 30 healthy controls. We found miR-185-5p significantly upregulated in ARVC patients. Receiver operating characteristic analysis indicated an area under the curve of 0.854, corroborating the link of this miRNA and ARVC pathophysiology.

Immunotoxins are protein-based drugs consist of a target-specific binding domain and a cytotoxic domain to eliminate target cells. Such compounds are potentially therapeutic to combat diseases such as cancer. Generally, the B-subunit of Shiga toxin (STXB) receptor, globotriaosylceramide (Gb3), is expressed in high amounts on a number of human tumors cancer cells. In this study, we evaluated a new antitumor candidate called DT389-STXB chimeric protein, which genetically fused the DT to B-subunit of Shiga-like toxin (STXB). First a chimeric protein, encoding DT389-STXB was synthesized. The optimized chimeric protein expressed in E.coli BL21 (DE3) and confirmed by anti-His Western blot analysis. T47D, SKBR3, 4T1 and MCF7 cell lines were treated separately with purified DT389-STXB recombinant protein and functional activity of DT389-STXB was analyzed by the cell enzyme-linked immunosorbentassay (ELISA), MTT, ICC, Western blot and apoptosis tests. The results indicated that the recombinant DT389-STXB fusion protein with a molecular weight of 53 kDa was successfully expressed in E.coli BL21 (DE3) and the anti-His western-blot was used to confirm the presence of the protein. The DT389-STXB fusion protein attached to T47D, SKBR3 and 4T1 cell lines with the proper affinity and induced dose-dependent cytotoxicity against GB3-expressing cancer cells in vitro. Our results showed that DT389-STXB fusion protein may be a promising candidate for antitumor therapy agent against breast cancer; however, further studies are required to explore its efficacy in vivo for therapeutic applications., (Copyright © 2021. Published by Elsevier B.V.)

Preeclampsia (PE) is strongly associated with heart failure (HF) later in life. The aberrant cardiac remodelling is likely initiated or amplified during preeclamptic pregnancy. Aberrant remodelling often persists after delivery and is known to relate strongly to cardiac fibrosis. This review provides an overview of pro- and anti- fibrotic circulating effector molecules that are involved in cardiac fibrosis and their association with PE. Women with PE complicated pregnancies show increased ANG-II sensitivity and elevated levels of the pro-fibrotic factors IL-6, TNF-α, TGs and FFAs compared to uncomplicated pregnancies. In the postpartum period, PE pregnancies compared to uncomplicated pregnancies have increased ANG-II sensitivity, elevated levels of the pro-fibrotic factors IL-6, TNF-α, LDL cholesterol and leptin, as well as decreased levels of the anti-fibrotic factor adiponectin. The review revealed several profibrotic molecules that associate to cardiac fibrosis during and after PE. The role that these fibrotic factors have on the heart during and after PE may improve the understanding of the link between PE and HF. Furthermore they may provide insight into the pathways in which the relation between both diseases can be understood as potential mechanisms which interfere in the process of cardiovascular disease (CVD). Unravelling the molecular mechanism and pathways involved might bring the diagnostic and therapeutic abilities of those factors a step closer., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: Pregnancy complicated by preeclampsia and fetal growth restriction (FGR) relates to increased risk of cardiovascular disease later in life, but to different extents. Subclinical cardiac alterations precede eminent cardiovascular disease. Speckle-tracking echocardiography is an elegant method to assess subclinical myocardial dysfunction. We performed a myocardial speckle tracking study to evaluate the prevalence of subclinical myocardial dysfunction in former preeclampsia patients (with and without FGR) compared with normotensive women with FGR., Methods: For this cross-sectional study, we retrospectively selected women with a history of normotensive FGR (n = 17), preeclampsia with FGR (n = 26) and preeclampsia without FGR (n = 134) who underwent conventional echocardiography as part of the clinical cardiovascular work-up after complicated pregnancies between 6 months and 4 years postpartum in Maastricht, The Netherlands. We excluded women with chronic hypertension, hypercholesterolemia and obesity., Results: Women with normotensive FGR showed subclinical left ventricular (LV) impairment in systodiastolic function with concentric remodeling, slight alteration in right ventricular systolic function and left atrial strain, similarly to the preeclampsia group independently from the fetal growth. LV hypertrophy was only present in about 10% of cases who experienced preeclampsia (independently from the fetal growth) but not in those with normotensive FGR., Conclusion: Similar to women with a history preeclampsia, women with a history of normotensive pregnancy but with FGR have abnormal myocardial function, shown with speckle-tracking echocardiography. Therefore, both preeclampsia and normotensive FGR should be viewed upon as risk indicator for subclinical myocardial impairment that may benefit from cardiovascular risk management.

Obesity leads to an amplified risk of disease and contributes to the occurrence of type 2 diabetes, fatty liver disease, coronary heart disease, stroke, chronic kidney disease and various types of cancer. MicroRNAs (miRNAs), small non-coding RNA molecules of 20-25 nucleotides, can remain stable in plasma and have been studied as potential (predictive) biomarkers for obesity and related metabolic disorders. The aim of this study was to identify circulating miRNAs as biomarkers for obesity status and metabolic alterations in women. Circulating miR-216a and miR-155-5p were selected by miRNA expression profiling and validated by real time quantitative PCR in a validation cohort of 60 obese women and 60 normal weight-age-matched control women. This was supplemented by correlation analysis of the candidate miRNA and anthropometric variables, blood biochemistry and lipid profile markers. Circulating miR-216a was validated as a biomarker of obesity status with significantly reduced levels in obese women. Interestingly, this was associated with a negative correlation between the plasma miR-216a content and body mass index (BMI), waist circumference, mean arterial pressure (MAP), triglycerides, ratio of total cholesterol/high density lipoprotein (HDL)-cholesterol and high sensitivity-C reactive protein (hs-CRP).Taken together, we provide evidence for an abnormally expressed circulating miRNA, miR-216a, with additive value as a predictive marker for obesity that correlates with metabolic alterations presented by lipid profile and inflammatory markers., Competing Interests: P.D.C.M and L.D.W are co-founders and stockholders of Mirabilis Therapeutics BV. TT is founder and shareholder of Cardior Pharmaceuticals GmbH. All other authors declare no conflict of interest., (© 2020 [The Author/The Authors].)

Cell-cell fusion or syncytialization is fundamental to the reproduction, development, and homeostasis of multicellular organisms. In addition to various cell type-specific fusogenic proteins, cell surface externalization of phosphatidylserine (PS), a universal eat-me signal in apoptotic cells, has been observed in different cell fusion events. Nevertheless, the molecular underpinnings of PS externalization and cellular mechanisms of PS-facilitated cell-cell fusion are unclear. Here, we report that TMEM16F, a Ca 2+ -activated phospholipid scramblase (CaPLSase), plays an essential role in placental trophoblast fusion by translocating PS to cell surface independent of apoptosis. The placentas from the TMEM16F knockout mice exhibit deficiency in trophoblast syncytialization and placental development, which lead to perinatal lethality. We thus identified a new biological function of TMEM16F CaPLSase in trophoblast fusion and placental development. Our findings provide insight into understanding cell-cell fusion mechanism of other cell types and on mitigating pregnancy complications such as miscarriage, intrauterine growth restriction, and preeclampsia., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)

Angiogenesis is a regulated process involving the proliferation, migration, and remodeling of different cell types particularly mature endothelial and their progenitor cells, nominated as endothelial progenitor cells (EPCs). Tie2/Tek is a tyrosine kinase receptor expressed by endothelial cells that induces signal transduction pathways involved in endothelial biology. To address the potential importance of the various tyrosine residues of Tie2 in EPC development, we generated a series of Tie2 tyrosine mutated (Y1106F, Y1100F, and Y1111F) EPCs and then assess the biological features of these cells. Clonogenic, tubulogenic, proliferative, migratory, and functional properties of these cells were analyzed. Next, GFP-positive EPCs containing Tie2 tyrosine mutations were systemically transplanted into sublethaly irradiated mice to analyze the potency of these cells for marrow reconstitution. We found that mutation in the Tie2 tyrosine 1106 residue directed EPCs toward a mature endothelial phenotype, which was associated with augmented tubulogenic and migratory properties, and increased phosphorylation of the active site (tyrosine 992) as well as increased vascular perfusion in the in vivo Matrigel plug assay. Moreover, transplantation of 1106 Tie2 mutant EPCs failed to reconstitute the bone marrow after myeloablation, whereas transplantation of EPCs with the 1100 or 1111 Tie2 tyrosine mutation resulted in bone marrow engraftment, leading to improved survival of recipient mice. Our findings demonstrate that the tyrosine 1106 residue in Tie2 plays a key role to maintain the stemness features of EPCs., (© 2018 Wiley Periodicals, Inc.)

Background: This study aimed to assess the effect of exposure parameters such as milliampere (mA) and field of view (FOV) of cone beam computed tomography (CBCT) on a metal artifact of dental implants placed in different bone densities., Methods: A total of 27 bone blocks with different densities (nine were type 1, nine were types 2 and 3, and nine were type 4) were used in this in vitro, experimental study. These blocks were placed in mandibular wax models. The blocks were scanned after drilling (hole preparation) and after implant placement using Cranex3D imaging system with a 4 × 6 cm 2 and 6 × 8 cm 2 FOV and 4 and 10 mA. Gray value of the bone blocks was recorded before and after placement of implants., Results: In general, irrespective of bone density, the amount of artifacts was lower in small FOV compared to large FOV (P < 0.05). Change of mA had no effect on metal artifacts (P > 0.05). Artifacts in type 4 bone were greater than in other bone types (P < 0.05). Difference between type 1 and types 2 and 3 was not significant (P > 0.05)., Conclusion: According to the results of this study, Peri-implant artifacts were seen in all bone types; the amount of artifacts in type 4 bone was higher than that in other types. Size of FOV and bone density affect the metal artifacts around dental implants; so that a smaller FOV can be used to decrease metal artifacts.

Background: The ability of low dose dobutamine (LDD) has been established in exploiting the reserved contractility of ischemic myocardium. This study was designed to assess the value of a new protocol, with an additional stress imaging during LDD infusion instead of the rest images, for evaluation of coronary artery disease (CAD) and perfusion reversibility., Methods: A total of 51 patients (42 men, 9 women; 57.2 +/- 11.3 years) were included in the study and underwent three sequential steps of imaging; the first step-stress gated SPECT with Tc-99m sestamibi, immediately followed by the second step-gated SPECT during constant infusion of 7.5 microg/kg/min dobutamine and finally the third step-rest phase scan following trinitroglycerine administration in the next day. The findings were interpreted using the images in three sets of display; first vs. second step-single injection-double acquisition gated SPECT before and during LDD (SIDAGS-LDD), first vs. third step-standard stress/rest protocol, and only first step-gated stress-only SPECT. In all cases, the Visual perfusion index of each protocols were calculated by summating the premeditated 5-point scale (5: normal, 4: completely reversible, 3: partially reversible, 2: nontransmural fixed and 1: transmural fixed defects) of 17 standard myocardial segments. The accuracy as well as the correlation and agreement of protocols for detecting perfusion abnormality and corresponding reversibility were statistically analyzed., Results: Calculated sensitivity, specificity, positive predictive value, negative predictive value and accuracy regarding the presence of CAD in both SIDAGS-LDD and standard protocols were 90.9% (40/44), 71.4% (5/7), 95.2% (40/42), 55.6% (5/9) and 88.2% (45/51), respectively. The extent and localization of perfusion abnormality with the new protocol were correlated well with standard method. The estimation of reversibility, however, was considerably improved by SIDAGS-LDD, especially in those with history of previous myocardial infarction (MI)., Conclusion: Our proposed protocol demonstrates good correlation and agreement with standard method and even is superior in some cases especially for estimation of viability after MI. Regarding no need for the rest phase radiotracer injection and imaging, this protocol can be more convenient (except the need for close monitoring of the patient during LDD infusion), less time-consuming, less expensive and moreover with less radiation burden to the patients and personnel.