LYL1 facilitates AETFC assembly and gene activation by recruiting CARM1 in t(8;21) AML.

Transcription factors (TFs) play critical roles in hematopoiesis, and their aberrant expression can lead to various types of leukemia. The t(8;21) leukemogenic fusion protein AML1-ETO (AE) is the most common fusion protein in acute myeloid leukemia and can enhance hematopoietic stem cell renewal while blocking differentiation. A key question in understanding AE-mediated leukemia is what determines the choice of AE to activate self-renewal genes or repress differentiation genes. Toward the resolution of this problem, we earlier showed that AE resides in the stable AETFC complex and that its components colocalize on up- or down-regulated target genes and are essential for leukemogenesis. In the current study, using biochemical and genomic approaches, we show that AE-containing complexes are heterogeneous, and that assembly of the larger AETFC (containing AE, CBFß, HEB, E2A, LYL1, LMO2, and LDB1) requires LYL1. Furthermore, we provide strong evidence that the LYL1-containing AETFC preferentially binds to active enhancers and promotes AE-dependent gene activation. Moreover, we show that coactivator CARM1 interacts with AETFC and facilitates gene activation by AETFC. Collectively, this study describes a role of oncoprotein LYL1 in AETFC assembly and gene activation by recruiting CARM1 to chromatin for AML cell survival.

DOT1L complex regulates transcriptional initiation in human erythroleukemic cells.

DOT1L, the only H3K79 methyltransferase in human cells and a homolog of the yeast Dot1, normally forms a complex with AF10, AF17, and ENL or AF9, is dysregulated in most cases of mixed-lineage leukemia (MLLr), and has been believed to regulate transcriptional elongation on the basis of its colocalization with RNA polymerase II (Pol II), the sharing of subunits (AF9 and ENL) between the DOT1L and super elongation complexes, and the distribution of H3K79 methylation on both promoters and transcribed regions of active genes. Here we show that DOT1L depletion in erythroleukemic cells reduces its global occupancy without affecting the traveling ratio or the elongation rate (assessed by 4sUDRB-seq) of Pol II, suggesting that DOT1L does not play a major role in elongation in these cells. In contrast, analyses of transcription initiation factor binding reveal that DOT1L and ENL depletions each result in reduced TATA binding protein (TBP) occupancies on thousands of genes. More importantly, DOT1L and ENL depletions concomitantly reduce TBP and Pol II occupancies on a significant fraction of direct (DOT1L-bound) target genes, indicating a role for the DOT1L complex in transcription initiation. Mechanistically, proteomic and biochemical studies suggest that the DOT1L complex may regulate transcriptional initiation by facilitating the recruitment or stabilization of transcription factor IID, likely in a monoubiquitinated H2B (H2Bub1)-enhanced manner. Additional studies show that DOT1L enhances H2Bub1 levels by limiting recruitment of the Spt-Ada-Gcn5-acetyltransferase (SAGA) complex. These results advance our understanding of roles of the DOT1L complex in transcriptional regulation and have important implications for MLLr leukemias.

Evaluation of the effects of duloxetine treatment on anterior segment parameters by optical coherence tomography.

PURPOSE: To evaluate the effects of Duloxetine on anterior segment parameters and intraocular pressure (IOP) in open angle eyes. METHODS: 38 eyes of 38 patients with fibromyalgia who had open or wide open angles according to the Shaffer classification. Anterior segment optic coherence tomography was performed before and after (month 3) Duloxetine treatment. IOP, central corneal thickness (CCT), corneal endothelial cell density (CECD) and anterior chamber depth (ACD) were also recorded and evaluated. RESULTS: No statistically significant difference was determined in IOP, CCT and CECD (p > 0.05). However, a statistically significant decrease was determined in both the temporal and nasal anterior chamber angle, angle opening distance, nasal trabecular-iris space area and ACD values between the baseline and month 3 (p < 0.001). DISCUSSION: We think that the short term use of Duloxetine does not lead to clinically significant changes despite their statistically significant effects on the anterior chamber parameters.

Measuring and regulating oxygen levels in microphysiological systems: design, material, and sensor considerations.

As microfabrication techniques and tissue engineering methods improve, microphysiological systems (MPS) are being engineered that recapitulate complex physiological and pathophysiological states to supplement and challenge traditional animal models. Although MPS provide unique microenvironments that transcend common 2D cell culture, without proper regulation of oxygen content, MPS often fail to provide the biomimetic environment necessary to activate and investigate fundamental pathways of cellular metabolism and sub-cellular level. Oxygen exists in the human body in various concentrations and partial pressures; moreover, it fluctuates dramatically depending on fasting, exercise, and sleep patterns. Regulating oxygen content inside MPS necessitates a sensitive biological sensor to quantify oxygen content in real-time. Measuring oxygen in a microdevice is a non-trivial requirement for studies focused on understanding how oxygen impacts cellular processes, including angiogenesis and tumorigenesis. Quantifying oxygen inside a microdevice can be achieved via an array of technologies, with each method having benefits and limitations in terms of sensitivity, limits of detection, and invasiveness that must be considered and optimized. This article will review oxygen physiology in organ systems and offer comparisons of organ-specific MPS that do and do not consider oxygen microenvironments. Materials used in microphysiological models will also be analyzed in terms of their ability to control oxygen. Finally, oxygen sensor technologies are critically compared and evaluated for use in MPS.

Quantum Tunneling Mediated Interfacial Synthesis of a Benzofuran Derivative.

Reaction pathways involving quantum tunneling of protons are fundamental to chemistry and biology. They are responsible for essential aspects of interstellar synthesis, the degradation and isomerization of compounds, enzymatic activity, and protein dynamics. On-surface conditions have been demonstrated to open alternative routes for organic synthesis, often with intricate transformations not accessible in solution. Here, we investigate a hydroalkoxylation reaction of a molecular species adsorbed on a Ag(111) surface by scanning tunneling microscopy complemented by X-ray electron spectroscopy and density functional theory. The closure of the furan ring proceeds at low temperature (down to 150 K) and without detectable side reactions. We unravel a proton-tunneling-mediated pathway theoretically and confirm experimentally its dominant contribution through the kinetic isotope effect with the deuterated derivative.

Ganciclovir ophthalmic gel treatment shortens the recovery time and prevents complications in the adenoviral eye infection.

The purpose of this study was to determine the effectiveness of ganciclovir ophthalmic gel (GOG) in the treatment of adenoviral eye infection (AEI) by looking at the effect of the drug on shortening recovery time, preventing transmission, reducing sequelae, and on complications such as corneal infiltrates and conjunctival pseudomembranes. 200 patients' examination records were evaluated retrospectively. Patients who were within the first 3 days of AEI were divided into two groups: Group 1 with 100 patients who used artificial tears as treatment, and Group 2 with 100 patients who used GOG plus artificial tears (GAT). All patients underwent an eye examination by the same ophthalmologist on the 1st, 5th, 10th, and 15th day after treatment. Using the examination records, variables were compared using SPSS 22.0. There was a statistically significant difference between Groups 1 and 2. Group 2 showed better and faster response to treatment. There was less transmission to the contralateral eye and environment, and less formation of corneal subepithelial infiltrate and conjunctival pseudomembrane in Group 2. Only three patients in Group 2 had corneal involvement. A comparison of each group pre-treatment and during treatment revealed improved signs and symptoms in Group 2 (p < 0.005). The study showed a trend toward more rapid improvement, less corneal and conjunctival involvement, and less transmission to the contralateral eye and environment in the GAT group. These results need to be confirmed by additional studies.

Nuclear deadenylation/polyadenylation factors regulate 3' processing in response to DNA damage.

We previously showed that mRNA 3' end cleavage reaction in cell extracts is strongly but transiently inhibited under DNA-damaging conditions. The cleavage stimulation factor-50 (CstF-50) has a role in this response, providing a link between transcription-coupled RNA processing and DNA repair. In this study, we show that CstF-50 interacts with nuclear poly(A)-specific ribonuclease (PARN) using in vitro and in extracts of UV-exposed cells. The CstF-50/PARN complex formation has a role in the inhibition of 3' cleavage and activation of deadenylation upon DNA damage. Extending these results, we found that the tumour suppressor BARD1, which is involved in the UV-induced inhibition of 3' cleavage, strongly activates deadenylation by PARN in the presence of CstF-50, and that CstF-50/BARD1 can revert the cap-binding protein-80 (CBP80)-mediated inhibition of PARN activity. We also provide evidence that PARN along with the CstF/BARD1 complex participates in the regulation of endogenous transcripts under DNA-damaging conditions. We speculate that the interplay between polyadenylation, deadenylation and tumour-suppressor factors might prevent the expression of prematurely terminated messengers, contributing to control of gene expression under different cellular conditions.

Diagnosis and Treatment Patterns of Chronic Thromboembolic Pulmonary Hypertension in Russia, Kazakhstan, Turkey, Lebanon, and Saudi Arabia: A Registry Study.

BACKGROUND: Patients with chronic thromboembolic pulmonary hypertension (CTEPH) in countries with limited resources have, to date, been poorly represented in registries. OBJECTIVE: This work assesses the epidemiology, diagnosis, hemodynamic and functional parameters, and treatment of CTEPH in Russia, Kazakhstan, Turkey, Lebanon, and Saudi Arabia. METHODS: A prospective, cohort, phase IV, observational registry with 3-year follow-up (n = 212) in patients aged ≥ 18 years diagnosed with CTEPH was created. Clinical, hemodynamic, and functional parameters were obtained at an initial visit, follow-up visits, and a final visit at the end of 3 years' observation or end of follow-up. Data were recorded on electronic case report forms. Parameters evaluated included 6-minute walking distance (6MWD), use of pulmonary endarterectomy (PEA), balloon pulmonary angioplasty (BPA), pulmonary hypertension (PH)-targeted therapy, and survival. All statistical analyses were exploratory and descriptive, and were performed in the overall population. RESULTS: The most common symptoms were typical of those expected for CTEPH. Almost 90% of patients underwent right heart catheterization at diagnosis or initial study visit. In total, 66 patients (31%) underwent PEA before the initial visit; 95 patients (45%) were considered operable, 115 (54%) were inoperable, and two (1%) had no operability data. Only 26 patients (12%) had been assessed for BPA at their initial visit. PH-targeted therapy was documented at diagnosis for 77 patients (36%), most commonly a phosphodiesterase type 5 inhibitor (23%). Use of PH-targeted therapy increased to 142 patients (67%) at the initial visit, remaining similar after 3 years. Use of riociguat increased from 6% of patients at diagnosis to 38% at 3 years. Between baseline and end of observation, results for patients with paired data showed an increase in 6MWD. Survival at the end of observation was 88%. CONCLUSIONS: These data highlight the current diagnosis and management of CTEPH in the participating countries. They show that early CTEPH diagnosis remains challenging, and use of off-label PH-targeted therapy is common. CLINICALTRIALS: gov: NCT02637050; registered December 2015.

Medium-sized tandem repeats represent an abundant component of the Drosophila virilis genome.

BACKGROUND: Previously, we developed a simple method for carrying out a restriction enzyme analysis of eukaryotic DNA in silico, based on the known DNA sequences of the genomes. This method allows the user to calculate lengths of all DNA fragments that are formed after a whole genome is digested at the theoretical recognition sites of a given restriction enzyme. A comparison of the observed peaks in distribution diagrams with the results from DNA cleavage using several restriction enzymes performed in vitro have shown good correspondence between the theoretical and experimental data in several cases. Here, we applied this approach to the annotated genome of Drosophila virilis which is extremely rich in various repeats. RESULTS: Here we explored the combined approach to perform the restriction analysis of D. virilis DNA. This approach enabled to reveal three abundant medium-sized tandem repeats within the D. virilis genome. While the 225 bp repeats were revealed previously in intergenic non-transcribed spacers between ribosomal genes of D. virilis, two other families comprised of 154 bp and 172 bp repeats were not described. Tandem Repeats Finder search demonstrated that 154 bp and 172 bp units are organized in multiple clusters in the genome of D. virilis. Characteristically, only 154 bp repeats derived from Helitron transposon are transcribed. CONCLUSION: Using in silico digestion in combination with conventional restriction analysis and sequencing of repeated DNA fragments enabled us to isolate and characterize three highly abundant families of medium-sized repeats present in the D. virilis genome. These repeats comprise a significant portion of the genome and may have important roles in genome function and structural integrity. Therefore, we demonstrated an approach which makes possible to investigate in detail the gross arrangement and expression of medium-sized repeats basing on sequencing data even in the case of incompletely assembled and/or annotated genomes.

Stakeholder perspectives on European priorities for comprehensive liver cancer control: a conjoint analysis.

BACKGROUND: As liver cancer incidence and mortality remain high in many parts of Europe, a more comprehensive response is required to reduce the burden. Expert stakeholders should be involved in the design of responses because they have important insights about potentially effective responses and will be affected by policy changes. We aimed to prioritize liver cancer control strategies based on European liver cancer stakeholders' views of which strategies would have the greatest impact in a comprehensive liver cancer control plan. METHODS: One hundred liver cancer clinical, policy and advocacy stakeholders from France, Germany, Italy, Spain and Turkey were surveyed. Respondents completed 12 conjoint choice tasks in which they chose which of two subsets of 11 strategies would have the greatest impact in their country. RESULTS: All strategies were considered likely to have a positive impact (P < 0.01). The highest priority strategy was monitoring of at-risk populations, followed by centres of excellence, clinical education, multidisciplinary management, national guidelines, measuring social burden, public awareness, risk assessment and referral, research infrastructure and access to treatments. CONCLUSIONS: Canvassing stakeholder views through a conjoint analysis survey provided a robust quantitative prioritization that can complement traditional qualitative consultation processes. The prioritized strategies provide a logical starting point for decision makers considering developing national plans or collaborative efforts to achieve comprehensive liver cancer control in Europe.

Does an increase in working hours affect mortality risk? The relationship between working hours and mortality among the older population.

BACKGROUND: Population aging, caused by an increase in life expectancy and decrease in fertility rates, has created changes and challenges in various spheres, including the labor market. Though health deteriorates with age, more and more older adults choose to stay in the labor force and work into late life. OBJECTIVE: Understanding the effects of various work conditions on the health of older workers is crucial for designing policies and interventions to ensure healthy late life and maintain a productive workforce. To contribute to this endeavor, this study investigates the relationship between long working hours (LWH) and mortality among older populations. METHODS: The study uses the Cox proportional hazards regression model to investigate data from the Health and Retirement Survey (HRS) between the years 1992-2016, a longitudinal nationally representative dataset from the United States. RESULTS: The results indicate that working 50 hours or more per week is not associated with an increased risk of mortality, for the full sample (1.45 [95% CI: 0.86, 2.45]), for both genders (females 0.51 [95% CI: 0.06, 4.28], males 1.45 [95% CI: 0.81, 2.61]), and for immigrants (female immigrants 0.55 [95% CI: 0.06, 4.75], male immigrants 1.44 [95% CI: 0.79, 2.62]). CONCLUSIONS: This analysis confirms and extends the findings of earlier studies by taking into consideration the potential impact of many demographic, socioeconomic, work-related and health-related factors.

Wireless Wearable Electrochemical Sensing Platform with Zero-Power Osmotic Sweat Extraction for Continuous Lactate Monitoring.

Wearable and wireless monitoring of biomarkers such as lactate in sweat can provide a deeper understanding of a subject's metabolic stressors, cardiovascular health, and physiological response to exercise. However, the state-of-the-art wearable and wireless electrochemical systems rely on active sweat released either via high-exertion exercise, electrical stimulation (such as iontophoresis requiring electrical power), or chemical stimulation (such as by delivering pilocarpine or carbachol inside skin), to extract sweat under low-perspiring conditions such as at rest. Here, we present a continuous sweat lactate monitoring platform combining a hydrogel for osmotic sweat extraction, with a paper microfluidic channel for facilitating sweat transport and management, a screen-printed electrochemical lactate sensor, and a custom-built wireless wearable potentiostat system. Osmosis enables zero-electrical power sweat extraction at rest, while continuous evaporation at the end of a paper channel allows long-term sensing from fresh sweat. The positioning of the lactate sensors provides near-instantaneous sensing at low sweat volume, and the custom-designed potentiostat supports continuous monitoring with ultra-low power consumption. For a proof of concept, the prototype system was evaluated for continuous measurement of sweat lactate across a range of physiological activities with changing lactate concentrations and sweat rates: for 2 h at the resting state, 1 h during medium-intensity exercise, and 30 min during high-intensity exercise. Overall, this wearable system holds the potential of providing comprehensive and long-term continuous analysis of sweat lactate trends in the human body during rest and under exercising conditions.

Radon transport in permeable geological environments.

This article presents the results of a long-term soil radon and meteorological parameter monitoring study in the fault zone at Mt. Beshtau, North Caucasus, which for more than 3 years. Strong seasonal variations in the radon levels with maxima during summer and minima during winter were recorded. The values of radon exhalation and soil radon concentration have a range of 0.025-25 Bq m 2 s -1 and 1-170 kBq m -3, respectively. In addition, measurements of the air radon concentration, and direction of air movement at the adits mouths of the former uranium mine on the same mountain were carried out. Seasonal radon variations, similar to those observed in fault zones, were recorded at the mouths of adits. It was established that radon anomalies are associated with the periodic release of mine air from the fractures and tunnels into the atmosphere. Above an altitude of 900 m a. s. l., an abnormal release of radon occurs in winter, when the mine air is warmer than the surrounding atmosphere. At the altitudes below 900 m the cold radon rich air blows from the adit mouths in summer. During mine air discharge, radon concentrations in the open atmosphere locally around the adit mouth reach 600,000 Bq m-3, averaging 50,000-250,000 Bq m-3. The temporal pattern of radon fluctuations in fault zones and at the adit mouths is similar. A very close correlation between radon levels and atmospheric air temperature was observed both in the fault zone and at the adits mouths. It indicates that radon release in both cases are caused by a single mechanism. This mechanism probably is the atmospheric air circulation in shallow permeable zones due to the temperature difference between the inside mountain and ambient atmosphere.

Opioids for cancer pain: availability, accessibility, and regulatory barriers in Turkey and Pallia-Turk Project.

Palliative care is an emerging topic in Turkey within recent years. Currently, there are only few number of palliative care services across the country and majority of the centers are pain control units. Morphine consumption rate per capita is low, accessibility and availability of morphine products are also limited. One of the main headings of Turkish Cancer Control Programme 2009-2015 is palliative care and a serial palliative care unit implementation with continuous training programmes is planned to be finalized until 2015. This article reviews the current palliative care situation in Turkey, opioid availability in Turkey and also briefly summarizes Pallia-Turk Project which is unique with respect to many different aspects for implementation, and can be a good model for many other countries that still did not have such an implemented palliative care program.

Integrated non-invasive biochemical and biophysical sensing systems for health and performance monitoring: A systems perspective.

Advances in materials, bio-recognition elements, transducers, and microfabrication techniques, as well as progress in electronics, signal processing, and wireless communication have generated a new class of skin-interfaced wearable health monitoring systems for applications in personalized medicine and digital health. In comparison to conventional medical devices, these wearable systems are at the cusp of initiating a new era of longitudinal and noninvasive sensing for the prevention, detection, diagnosis, and treatment of diseases at the molecular level. Herein, we provide a review of recent developments in wearable biochemical and biophysical systems. We survey the sweat sampling and collection methods for biochemical systems, followed by an assessment of biochemical and biophysical sensors deployed in current wearable systems with an emphasis on their hardware specifications. Specifically, we address how sweat collection and sample handling platforms may be a rate limiting technology to realizing the clinical translation of wearable health monitoring systems; moreover, we highlight the importance of achieving both longitudinal sensing and assessment of intrapersonal variation in sweat-blood correlations to have the greatest clinical impact. Lastly, we assess a snapshot of integrated wireless wearable systems with multimodal sensing capabilities, and we conclude with our perspective on the state-of-the-art and the required developments to achieve the next-generation of integrated wearable health and performance monitoring systems.

Rational design of direct electron transfer type l-lactate dehydrogenase for the development of multiplexed biosensor.

The development of wearable multiplexed biosensors has been focused on systems to measure sweat l-lactate and other metabolites, where the employment of the direct electron transfer (DET) principle is expected. In this paper, a fusion enzyme between an engineered l-lactate oxidase derived from Aerococcus viridans, AvLOx A96L/N212K mutant, which is minimized its oxidase activity and b-type cytochrome protein was constructed to realize multiplexed DET-type lactate and glucose sensors. The sensor with a fusion enzyme showed DET to a gold electrode, with a limited operational range less than 0.5 mM. A mutation was introduced into the fusion enzyme to increase Km value and eliminate its substrate inhibition to construct "b2LOxS". Together with the employment of an outer membrane, the detection range of the sensor with b2LOxS was expanded up to 10 mM. A simultaneous lactate and glucose monitoring system was constructed using a flexible thin-film multiplexed electrodes with b2LOxS and a DET-type glucose dehydrogenase, and evaluated their performance in the artificial sweat. The sensors achieved simultaneous detection of lactate and glucose without cross-talking error, with the detected linear ranges of 0.5-20 mM for lactate and 0.1-5 mM for glucose, sensitivities of 4.1 nA/mM∙mm2 for lactate and 56 nA/mM∙mm2 for glucose, and limit of detections of 0.41 mM for lactate and 0.057 mM for glucose. The impact of the presence of electrochemical interferants (ascorbic acid, acetaminophen and uric acid), was revealed to be negligible. This is the first report of the DET-type enzyme based lactate and glucose dual sensing systems.

A Wearable Patch for Prolonged Sweat Lactate Harvesting and Sensing.

Operating at low sweat rates, such as those experienced by humans at rest, is still an unmet need for state-of-the-art wearable sweat harvesting and testing devices for lactate. Here, we report the on-skin performance of a non-invasive wearable sweat sampling patch that can harvest sweat at rest, during exercise, and post-exercise. The patch simultaneously uses osmosis and evaporation for long-term (several hours) sampling of sweat. Osmotic sweat withdrawal is achieved by skin-interfacing a hydrogel containing a concentrated solute. The gel interfaces with a paper strip that transports the fluid via wicking and evaporation. Proof of concept results show that the patch was able to sample sweat during resting and post-exercise conditions, where the lactate concentration was successfully quantified. The patch detected the increase in sweat lactate levels during medium level exercise. Blood lactate remained invariant with exercise as expected. We also developed a continuous sensing version of the patch by including enzymatic electrochemical sensors. Such a battery-free, passive, wearable sweat sampling patch can potentially provide useful information about the human metabolic activity.

The 3' processing factor CstF functions in the DNA repair response.

Following DNA damage, mRNA levels decrease, reflecting a coordinated interaction of the DNA repair, transcription and RNA processing machineries. In this study, we provide evidence that transcription and polyadenylation of mRNA precursors are both affected in vivo by UV treatment. We next show that the polyadenylation factor CstF, plays a direct role in the DNA damage response. Cells with reduced levels of CstF display decreased viability following UV treatment, reduced ability to ubiquitinate RNA polymerase II (RNAP II), and defects in repair of DNA damage. Furthermore, we show that CstF, RNAP II and BARD1 are all found at sites of repaired DNA. Our results indicate that CstF plays an active role in the response to DNA damage, providing a link between transcription-coupled RNA processing and DNA repair.

Wearable multiplexed biosensor system toward continuous monitoring of metabolites.

Comprehensive metabolic panels are the most reliable and common methods for monitoring general physiology in clinical healthcare. Translation of this clinical practice to personal health and wellness tracking requires reliable, non-invasive, miniaturized, ambulatory, and inexpensive systems for continuous measurement of biochemical analytes. We report the design and characterization of a wearable system with a flexible sensor array for non-invasive and continuous monitoring of human biochemistry. The system includes signal conditioning, processing, and transmission parts for continuous measurement of glucose, lactate, pH, and temperature. The system can operate three discrete electrochemical cells. The system draws 15 mA under continuous operation when powered by a 3.7 V 150 mAh battery. The analog front-end of the electrochemical cells has four potentiostats and three multiplexers for multiplexed and parallel readout from twelve working electrodes. Utilization of redundant working electrodes improves the measurement accuracy of sensors by averaging chronoamperometric responses across the array. The operation of the system is demonstrated in vitro by simultaneous measurement of glucose and lactate, pH, and skin temperature. In benchtop measurements, the sensors are shown to have sensitivities of 26.31 µA mM-1·cm-2 for glucose, 1.49 µA mM-1·cm-2 for lactate, 54 mV·pH-1 for pH, and 0.002 °C-1 for temperature. With the custom wearable system, these values were 0.84 ± 0.03 mV µM-1·cm-2 or glucose, 31.87 ± 9.03 mV mM-1·cm-2 for lactate, 57.18 ± 1.43 mV·pH-1 for pH, and 63.4 µV·°C-1 for temperature. This miniaturized wearable system enables future evaluation of temporal changes of the sweat biomarkers.

Amniotic fluid levels of selected trace elements and heavy metals in pregnancies complicated with neural tube defects.

The aims of this study were to determine the levels of trace elements and heavy metals, namely aluminum (Al), chromium (Cr), manganese (Mn), cobalt (Co), nickel (Ni), copper (Cu), zinc (Zn), arsenic (As), molybdenum (Mo), cadmium (Cd), tin (Sn), antimony (Sb), mercury (Hg), and lead (Pb), in the amniotic fluid of pregnant women, and to investigate their relationship with neural tube defects (NTDs). The study included 36 pregnant women whose fetuses were complicated with NTDs (study group) and 39 pregnant women with unaffected healthy fetuses (control group), who were matched for body mass index and gestational weeks. The amniotic fluid levels of trace elements and heavy metals were measured using inductively coupled plasma-mass spectrometry and compared between the two groups. Significantly lower mean levels of Zn and Mo and significantly higher levels of Al, Sn, Sb, and Hg in the study group than in the healthy control group were observed, which implied that these elements are possibly correlated with risk factors for the occurrence of NTDs. In contrast, there were no significant differences in the levels of Cr, Mn, Co, Ni, Cu, As, Cd, and Pb between the groups (P ≥ .05).