In vitro toxicity and chemical analysis of e-cigarette aerosol produced amid dry hitting.

Dry hitting, a phenomenon produced by e-cigarettes with refillable cartridges when the liquid in the coil is low, is a common occurrence among regular vapers despite being an unintended consequence of the device. This phenomenon's hazard to public health is still unknown and needs further investigation. Lung cells cultured at the air-liquid interface were exposed to vaped aerosol consisting of 3 % w/v ethyl maltol in propylene glycol for three-second puffs every 30 seconds for 80 total puffs with either dry hit or saturated conditions. Cytotoxicity was measured colorimetrically. The thermal degradation of the heating coils and wicks was visualized using scanning electron microscopy. The chemical byproducts in the aerosol were analyzed using proton nuclear magnetic resonance and inductively coupled plasma mass spectrometry. The results revealed a highly significant increase in cytotoxicity from dry hit treatments. Imaging showed thermal decomposition of the cotton wick after dry hitting, which was confirmed by energy dispersive x-ray spectroscopy with less oxygen in the dry hit cotton. Chemical byproducts were found via unique peaks in the dry hit condensate in the aromatic and alkene regions. Saturated condensate showed higher concentrations of detected metal species than dry-hit condensate. E-cigarette users should avoid dry hitting by refilling tanks or cartridges preemptively or by using disposable coils to avoid increased toxicity during vaping.

The HGF/Met Receptor Mediates Cytotoxic Effect of Bacterial Cyclodipeptides in Human Cervical Cancer Cells.

BACKGROUND: Human cervix adenocarcinoma (CC) caused by papillomavirus is the third most common cancer among female malignant tumors. Bioactive compounds such as cyclodipeptides (CDPs) possess cytotoxic effects in human cervical cancer HeLa cells mainly by blocking the PI3K/Akt/mTOR pathway and subsequently inducing gene expression by countless transcription regulators. However, the upstream elements of signaling pathways have not been well studied. METHODS: To elucidate the cytotoxic and antiproliferative responses of the HeLa cell line to CDPs by a transcriptomic analysis previously carried out, we identified by immunochemical analyses, differential expression of genes related to the hepatocyte growth factor/mesenchymal-epithelial transition factor (HGF/MET) receptors. Furthermore, molecular docking was carried out to evaluate the interactions of CDPs with the EGF and MET substrate binding sites. RESULTS: Immunochemical and molecular docking analyses suggest that the HGF/MET receptor participation in CDPs cytotoxic effect was independent of the protein expression levels. However, protein modulation of downstream Met-targets occurred due to the inhibition of phosphorylation of the HGF/MET receptor. Results suggest that the antiproliferative and cytotoxicity of CDPs in HeLa cells involve the HGF/MET receptor upstream of PI3K/Akt/mTOR pathway; assays with the human breast cancer MCF-7 and MDA-MB-231cell lines supported the finding. CONCLUSION: Data provide new insights into the molecular mechanisms involved in CDPs cytotoxicity and antiproliferative effects, suggesting that the signal transduction mechanism may be related to the inhibition of the phosphorylation of the EGF/MET receptor at the level of substrate binding site by an inhibition mechanism similar to that of Gefitinib and foretinib anti-neoplastic drugs.

Effect of Injury to the Lateral Meniscotibial Ligament and Meniscofibular Ligament on Meniscal Extrusion: Biomechanical Evaluation of the Capsulodesis and Centralization Techniques in a Porcine Knee Model.

Background: Previous biomechanical studies of the meniscotibial ligament have determined that it contributes to meniscal stability. An injury to it can cause the meniscus to extrude, and reconstruction of that ligament significantly reduces extrusion. Purpose: To assess the biomechanical effects of sectioning the lateral meniscotibial ligament (LMTL) and the meniscofibular ligament (MFL) with respect to the radial mobility of the lateral meniscus and to evaluate the biomechanical effects of the capsulodesis and centralization techniques. Study Design: Controlled laboratory study. Methods: The lateral meniscus of 22 porcine knees was evaluated. They were mounted on a testing apparatus to apply muscle and ground-reaction forces. The meniscus was evaluated at 30° and 60° of knee flexion using 2 markers placed on the posterior cruciate ligament and the lateral meniscus after applying an axial compression of 200 N to the knee joint. Measurements were recorded under 5 conditions: intact lateral meniscus, injury of the LMTL, subsequent injury of the MFL, the use of the open capsulodesis technique, and the reconstruction of the LMTL and the MFL with the centralization technique. Results: The distance between the 2 markers was significantly greater in the extrusion group (combined lesion of the LMTL and MFL) than in the intact or reconstruction groups (capsulodesis and centralization techniques; P < .001 in all cases). In the cases of load application, no significant differences were observed between the control group (intact meniscus) and the groups on which the reconstruction techniques were performed. There were also no differences when comparing the results obtained between both reconstruction techniques. In all settings, the distance between the 2 markers increased with the increase in the knee flexion angle. Conclusion: In a porcine model, the LMTL and the MFL participated as restrictors of the radial mobility of the lateral meniscus during loading. Their injury caused a significant increase in lateral meniscal extrusion, and the centralization and the capsulodesis procedures were able to reduce extrusion. Clinical Relevance: This study demonstrates the capacity of the LMTL and the MFL to restrict the radial mobility of the lateral meniscus during loading and how it is affected when they are injured.

Evaluation of water from Lake Coatetelco in central-south Mexico and surrounding groundwater wells for drinking and irrigation, and the possible health risks.

Due to an increasing reduction of hydrological resources across Mexico and their growing contamination from global warming and anthropogenic activities, this study evaluated water from the perennial Lake Coatetelco (Ca-Mg-HCO3) in tropical central-southern Mexico and groundwater (Ca-Mg-HCO3 and Na-HCO3-Cl) from the surrounding wells for drinking as well as irrigation qualities. Comparison with the WHO guidelines and the estimated water quality indices (DWQI and IWQI) grouped almost all the samples collected after the warm season rainfall in excellent and good categories (DWQI < 100) for drinking, even though fluoride remained > 1.5 mg/L in 50% samples. Except for one groundwater sample, all showed > 25% permeability (classes I and II) in Donnen classification indicating their suitability for irrigation. USSL and Wilcox classifications, however, catalogued some in the high-salinity hazard group and some as doubtful for irrigating regular plants. Samples from about 53% wells were also in high and severe restriction categories of IWQI for the irrigation. Total Hazard Quotient Index (THQI) for estimating the non-carcinogenic risk (HQfluoride > 1) showed that at least one lake water sample and 53% of groundwater might expose the adult and child population to dental and skeletal fluorosis. This water quality assessment data posterior to the rainfall season could be useful as a baseline for both the short- and long-term monitoring in attention to the United Nation's Sustainable Development Goal 6.

Lactate oxidation is linked to energy conservation and to oxygen detoxification via a putative terminal cytochrome oxidase in Methanosarcina acetivorans.

The marine archaeon Methanosarcina acetivorans contains a putative NAD + -independent d-lactate dehydrogenase (D-iLDH/glycolate oxidase) encoded by the MA4631 gene, belonging to the FAD-oxidase C superfamily. Nucleotide sequences similar to MA4631 gene, were identified in other methanogens and Firmicutes with >90 and 35-40% identity, respectively. Therefore, the lactate metabolism in M. acetivorans is reported here. Cells subjected to intermittent pulses of oxygen (air-adapted; AA-Ma cells) consumed lactate only in combination with acetate, increasing methane production and biomass yield. In AA-Ma cells incubated with d-lactate plus [14C]-l-lactate, the radioactive label was found in methane, CO2 and glycogen, indicating that lactate metabolism fed both methanogenesis and gluconeogenesis. Moreover, d-lactate oxidation was coupled to O2-consumption which was sensitive to HQNO; also, AA-Ma cells showed high transcript levels of gene dld and those encoding subunits A (MA1006) and B (MA1007) of a putative cytochrome bd quinol oxidase, compared to anaerobic control cells. An E. coli mutant deficient in dld complemented with the MA4631 gene, grew with d-lactate as carbon source and showed membrane-bound d-lactate:quinone oxidoreductase activity. The product of the MA4631 gene is a FAD-containing monomer showing activity of iLDH with preference to d-lactate. The results suggested that air adapted M. acetivorans is able to co-metabolize lactate and acetate with associated oxygen consumption by triggering the transcription and synthesis of the D-iLDH and a putative cytochrome bd: methanophenazine (quinol) oxidoreductase. Biomass generation and O2 consumption, suggest a potentially new oxygen detoxification mechanism coupled to energy conservation in this methanogen.

Thermomechanical Characterization and Modeling of NiTi Shape Memory Alloy Coil Spring.

Today, shape memory alloys (SMAs) have important applications in several fields of science and engineering. This work reports the thermomechanical behavior of NiTi SMA coil springs. The thermomechanical characterization is approached starting from mechanical loading-unloading tests under different electric current intensities, from 0 to 2.5 A. In addition, the material is studied using dynamic mechanical analysis (DMA), which is used to evaluate the complex elastic modulus E* = E' - iE″, obtaining a viscoelastic response under isochronal conditions. This work further evaluates the damping capacity of NiTi SMA using tan δ, showing a maximum around 70 °C. These results are interpreted under the framework of fractional calculus, using the Fractional Zener Model (FZM). The fractional orders, between 0 and 1, reflect the atomic mobility of the NiTi SMA in the martensite (low-temperature) and austenite (high-temperature) phases. The present work compares the results obtained from using the FZM with a proposed phenomenological model, which requires few parameters for the description of the temperature-dependent storage modulus E'.

Shotgun Proteomics of Co-Cultured Leukemic and Bone Marrow Stromal Cells from Different Species as a Preliminary Approach to Detect Intercellular Protein Transfer.

Cellular interactions within the bone marrow microenvironment modulate the properties of subsets of leukemic cells leading to the development of drug-resistant phenotypes. The intercellular transfer of proteins and organelles contributes to this process but the set of transferred proteins and their effects in the receiving cells remain unclear. This study aimed to detect the intercellular protein transfer from mouse bone marrow stromal cells (OP9 cell line) to human T-lymphoblasts (CCRF-CEM cell line) using nanoLC-MS/MS-based shotgun proteomics in a 3D co-culture system. After 24 h of co-culture, 1513 and 67 proteins from human and mouse origin, respectively, were identified in CCRF-CEM cells. The presence of mouse proteins in the human cell line, detected by analyzing the differences in amino acid sequences of orthologous peptides, was interpreted as the result of intercellular transfer. The transferred proteins might have contributed to the observed resistance to vincristine, methotrexate, and hydrogen peroxide in the co-cultured leukemic cells. Our results suggest that shotgun proteomic analyses of co-cultured cells from different species could be a simple option to get a preliminary survey of the proteins exchanged among interacting cells.

Health and Nutrition Analysis in Older Adults in San José de Minas Rural Parish in Quito, Ecuador.

Knowing the health and nutritional status of older adults is crucial to helping them live healthier lives and limiting the need for pharmaceuticals and complicated medical procedures. The objective of this research was to analyze the eating habits (EH), physical activity (PA), and sleep quality (SQ) of older adults in the rural parish of San José de Minas in Quito, Ecuador. Three validated questionnaires were used: the Pittsburgh PSQI for SQ, IPAQ for PA, and frequency of consumption for EH. The results revealed high consumption of refined flours and sugar (70% at least once a day), low intake of whole grains, fish, and olive oil, and considerable consumption of fruits and water. Fifty percent of respondents engage in moderate physical activity and 24% in low physical activity, while 90% of older adults have poor sleep quality. These results indicate a problem in the integral health of the population that does not allow older adults to have a good old age. Health campaigns should be developed to increase physical activity, encourage a better diet, and thus, improve the quality of sleep.

Cultivation of gastrointestinal microbiota in a new growth system revealed dysbiosis and metabolic disruptions in carcinoma-bearing rats.

A challenge in the study of gastrointestinal microbiota (GITm) is the validation of the genomic data with metabolic studies of the microbial communities to understand how the microbial networks work during health and sickness. To gain insights into the metabolism of the GITm, feces from healthy and sick rats with cancer were inoculated in a defined synthetic medium directed for anaerobic prokaryote growth (INC-07 medium). Significant differences between cultures of healthy and sick individuals were found: 1) the consumption of the carbon source and the enzyme activity involved in their catabolism (e.g., sucrase, lactase, lipases, aminotransferases, and dehydrogenases); 2) higher excretion of acetic, propionic, isobutyric, butyric, valeric, and isovaleric acids; 3) methane production; 4) ability to form biofilms; and 5) up to 500 amplicon sequencing variants (ASVs) identified showed different diversity and abundance. Moreover, the bowel inflammation induced by cancer triggered oxidative stress, which correlated with deficient antioxidant machinery (e.g., NADPH-producing enzymes) determined in the GITm cultures from sick individuals in comparison with those from control individuals. Altogether, the data suggested that to preserve the microbial network between bacteria and methanogenic archaea, a complete oxidation of the carbon source may be essential for healthy microbiota. The correlation of 16S rRNA gene metabarcoding between cultures and feces, as well as metabolomic data found in cultures, suggest that INC-07 medium may be a useful tool to understand the metabolism of microbiota under gut conditions.

A Brominated Furanone Inhibits Pseudomonas aeruginosa Quorum Sensing and Type III Secretion, Attenuating Its Virulence in a Murine Cutaneous Abscess Model.

Quorum sensing (QS) and type III secretion systems (T3SSs) are among the most attractive anti-virulence targets for combating multidrug-resistant pathogenic bacteria. Some halogenated furanones reduce QS-associated virulence, but their role in T3SS inhibition remains unclear. This study aimed to assess the inhibition of these two systems on Pseudomonas aeruginosa virulence. The halogenated furanones (Z)-4-bromo-5-(bromomethylene)-2(5H) (C-30) and 5-(dibromomethylene)-2(5H) (named hereafter GBr) were synthesized, and their ability to inhibit the secretion of type III exoenzymes and QS-controlled virulence factors was analyzed in P. aeruginosa PA14 and two clinical isolates. Furthermore, their ability to prevent bacterial establishment was determined in a murine cutaneous abscess model. The GBr furanone reduced pyocyanin production, biofilm formation, and swarming motility in the same manner or more effectively than C-30. Moreover, both furanones inhibited the secretion of ExoS, ExoT, or ExoU effectors in all tested strains. The administration of GBr (25 and 50 µM) to CD1 mice infected with the PA14 strain significantly decreased necrosis formation in the inoculation zone and the systemic spread of bacteria more efficiently than C-30 (50 µM). Molecular docking analysis suggested that the gem position of bromine in GBr increases its affinity for the active site of the QS LasR regulator. Overall, our findings showed that the GBr furanone displayed efficient multi-target properties that may favor the development of more effective anti-virulence therapies.

Benchmark Dose Modeling Approaches for Volatile Organic Chemicals Using a Novel Air-Liquid Interface In Vitro Exposure System.

Inhalation is the most relevant route of volatile organic chemical (VOC) exposure; however, due to unique challenges posed by their chemical properties and poor solubility in aqueous solutions, in vitro chemical safety testing is predominantly performed using direct application dosing/submerged exposures. To address the difficulties in screening toxic effects of VOCs, our cell culture exposure system permits cells to be exposed to multiple concentrations at air-liquid interface (ALI) in a 24-well format. ALI exposure methods permit direct chemical-to-cell interaction with the test article at physiological conditions. In the present study, BEAS-2B and primary normal human bronchial epithelial cells (pHBEC) are used to assess gene expression, cytotoxicity, and cell viability responses to a variety of volatile chemicals including acrolein, formaldehyde, 1,3-butadiene, acetaldehyde, 1-bromopropane, carbon tetrachloride, dichloromethane, and trichloroethylene. BEAS-2B cells were exposed to all the test agents, whereas pHBECs were only exposed to the latter 4 listed above. The VOC concentrations tested elicited only slight cell viability changes in both cell types. Gene expression changes were analyzed using benchmark dose (BMD) modeling. The BMD for the most sensitive gene set was within one order of magnitude of the threshold-limit value reported by the American Conference of Governmental Industrial Hygienists, and the most sensitive gene sets impacted by exposure correlate to known adverse health effects recorded in epidemiologic and in vivo exposure studies. Overall, our study outlines a novel in vitro approach for evaluating molecular-based points-of-departure in human airway epithelial cell exposure to volatile chemicals.

Fixed-bearing unicompartmental knee arthroplasty provides a lower failure rate than mobile-bearing unicompartimental knee arthroplasty when used after a failed high tibial osteotomy: a systematic review and meta-analysis.

Despite the fact that the choice of bearing design has been thought to influence the functional outcomes and longevity of unicompartimental knee arthroplasty (UKA), there is a lack of clinical evidence supporting the decision-making process in patients who have undergone high tibial osteotomy (HTO). A systematic review of studies was carried out that reported the outcomes of fixed-bearing (FB) or mobile-bearing (MB) medial UKA in patients with a previous HTO. A random effect meta-analysis using a generalized linear mixed-effects model to calculate revision rates was done. Seven retrospective cohort studies were included for this study. Regarding the fixation method, 40 were the FB-UKA and 47 were MB-UKA. For both groups, the mean post-operative follow-up was 5.8 years. The survival rates were 92% for the FB-UKA with a mean follow-up of 10 years. For the MB-UKA, it ranged from 35.7 to 93%, with a mean follow-up of 4.2 years. For the FB, the time to revision was reported as 9.3 years, while 1.2, 2.5 and 2.91 years was reported for the MB. The results of the meta-analysis showed that the revision rate for the patients receiving a FB-UKA after failed HTO was 8%, compared to 17% in those who received an MB-UKA. The results of the review suggest that the use of the FB-UKA is associated with lower revision rates and a longer survival time than the MB-UKA and have similar functional ability scores.Level of evidence: III (systematic review of level-III studies).

Geochemical evolution and seasonality of groundwater recharge at water-scarce southeast margin of the Chihuahuan Desert in Mexico.

Climate models for the 21st century project further reduction in the warm season precipitation and more frequent droughts across Mexico. In the possible scenario of enhanced aridity from global warming, the δ18O (-10.6 to -6.3 ‰) and δ2H (-71.1 to -57.1 ‰) compositions and deuterium-excess (0.2-14.6‰) of shallow groundwater from two different basins (Sandia and El Potosi) with similar geological and geomorphological settings were considered to evaluate the influences of early summer rainfall and later summer tropical storms on aquifers at water-scarce southeast margin of the Chihuahuan Desert. Groundwater of the Sandia Basin was recharged mainly from tropical storms. Higher CO2 partial pressure (log pCO2: -2.70 to -1.61) caused more gypsum dissolution (Ca-Mg-SO4 facies) and the effect of irrigation return flow (Ca-Mg-Cl facies) was minor. Even though the El Potosi Basin is in proximity, its groundwater was recharged from both the early and late summer precipitations. The multivariate factor analysis helped to separate the process of rock-water interactions from the recharge seasonality. Gypsum dissolution was less as the partial pressure of CO2 was comparatively lower (log pCO2: -3.01 to -2.15), and the ion exchange along with carbonate mineral dissolutions led to Ca-Mg-HCO3 facies. Over-exploitation under the condition of reduced warm season rainfall would continue to enhance the salinity of groundwater in this region. Hence, the drought mitigation policies should prioritize sustainability of the depleted aquifers and cultivation of salinity resistant crops.

Protein acetylation effects on enzyme activity and metabolic pathway fluxes.

Acetylation of proteins seems a widespread process found in the three domains of life. Several studies have shown that besides histones, acetylation of lysine residues also occurs in non-nuclear proteins. Hence, it has been suggested that this covalent modification is a mechanism that might regulate diverse metabolic pathways by modulating enzyme activity, stability, and/or subcellular localization or interaction with other proteins. However, protein acetylation levels seem to have low correlation with modification of enzyme activity and pathway fluxes. In addition, the results obtained with mutant enzymes that presumably mimic acetylation have frequently been over-interpreted. Moreover, there is a generalized lack of rigorous enzyme kinetic analysis in parallel to acetylation level determinations. The purpose of this review is to analyze the current findings on the impact of acetylation on metabolic enzymes and its repercussion on metabolic pathways function/regulation.

Application of telemedicine video visits in a maternal-fetal medicine practice at the epicenter of the COVID-19 pandemic.

BACKGROUND: Telemedicine in obstetrics has mostly been described in the rural areas that have limited access to subspecialties. During the COVID-19 pandemic, health systems rapidly expanded telemedicine services for urgent and nonurgent healthcare delivery, even in urban settings. The New York University health system implemented a prompt systemwide expansion of video-enabled telemedicine visits, increasing telemedicine to >8000 visits daily within 6 weeks of the beginning of the pandemic. There are limited studies that explore patient and provider satisfaction of telemedicine visits in obstetrical patients during the COVID-19 epidemic, particularly in the United States. OBJECTIVE: This study aimed to evaluate both the patients' and the providers' satisfaction with the administration of maternal-fetal medicine services through telemedicine and to identify the factors that drive the patients' desire for future obstetrical telemedicine services. STUDY DESIGN: A cross-sectional survey was administered to patients who completed a telemedicine video visit with the Division of Maternal-Fetal Medicine at the New York University Langone Hospital-Long Island from March 19, 2020, to May 26, 2020. A 10-question survey assessing the patients' digital experience and desire for future use was either administered by telephone or self-administered by the patients via a link after obtaining verbal consent. The survey responses were scored from 1-strongly disagree to 5-strongly agree. We analyzed the demographics and survey responses of the patients who agreed to vs those who answered neutral or disagree to the question "I would like telehealth to be an option for future obstetric visits." The providers also answered a similar 10-question survey. The median scores were compared using appropriate tests. A P value of <.05 was considered significant. RESULTS: A total of 253 patients participated in 433 telemedicine visits, and 165 patients completed the survey, resulting in a 65% survey response rate. Overall, there were high rates of patient satisfaction in all areas assessed. Those who desired future telemedicine had significantly greater agreeability that they were able to see and hear their provider easily (5 [4.5, 5] vs 5 [4, 5]; P=.014) and that the lack of physical activity was not an issue (5 [4, 5] vs 5 [4, 5]; P=.032). They were also more likely to agree that the telemedicine visits were as good as in-person visits (4 [3, 5] vs 3 [2, 3]; P<.001) and that telehealth made it easier for them to see doctors or specialists (5 [4, 5] vs 3 [2, 3]; P<.001). The patients seeking consults for poor obstetrical history were more likely to desire future telemedicine compared with other visit types (19 (90%) vs 2 (10%); P=.05). Provider survey responses also demonstrated high levels of satisfaction, with 83% agreeing that they would like telemedicine to be an option for future obstetrical visits. CONCLUSION: We demonstrated that maternal-fetal medicine obstetrical patients and providers were highly satisfied with the implementation of telemedicine during the initial wave of the COVID-19 pandemic and a majority of them desire telemedicine as an option for future visits. A patient's desire for future telemedicine visits was significantly affected by their digital experience, the perception of a lack of need for physical contact, perceived time saved on travel, and access to healthcare providers. Health systems need to continue to improve healthcare delivery and invest in innovative solutions to conduct physical examinations remotely.

Study of Friction and Wear Effects in Aluminum Parts Manufactured via Single Point Incremental Forming Process Using Petroleum and Vegetable Oil-Based Lubricants.

This paper focuses on studying how mineral oil, sunflower, soybean, and corn lubricants influence friction and wear effects during the manufacturing of aluminum parts via the single point incremental forming (SPIF) process. To identify how friction, surface roughness, and wear change during the SPIF of aluminum parts, Stribeck curves were plotted as a function of the SPIF process parameters such as vertical step size, wall angle, and tool tip semi-spherical diameter. Furthermore, lubricant effects on the surface of the formed parts are examined by energy dispersive spectroscopy (EDS) and scanning electron microscope (SEM) images, the Alicona optical 3D measurement system, and Fourier-transform infrared spectroscopy (FTIR). Results show that during the SPIF process of the metallic specimens, soybean and corn oils attained the highest friction, along forces, roughness, and wear values. Based on the surface roughness measurements, it can be observed that soybean oil produces the worst surface roughness finish in the direction perpendicular to the tool passes (Ra =1.45 µm) considering a vertical step size of 0.25 mm with a 5 mm tool tip diameter. These findings are confirmed through plotting SPIFed Stribeck curves for the soybean and corn oils that show small hydrodynamic span regime changes for an increasing sample step-size forming process. This article elucidates the effects caused by mineral and vegetable oils on the surface of aluminum parts produced as a function of Single Point Incremental Sheet Forming process parameters.

Use of cervical elastography at 18 to 22 weeks' gestation in the prediction of spontaneous preterm birth.

BACKGROUND: Accurate identification of the women who will have spontaneous preterm birth continues to be a great challenge. The use of cervical elastography for prediction of preterm birth is promising, but several limitations exist. Newer cervical elastography technology has been developed that may prove useful in evaluation of risk of preterm birth. OBJECTIVE: This study aimed to develop standard cervical elastography nomograms for singleton pregnancies at 18 to 22 weeks' gestation using the E-Cervix ultrasound application, assess intraobserver reliability of the E-Cervix elastography parameters, and determine whether these cervical elastography measurements can be used in the prediction of spontaneous preterm birth. STUDY DESIGN: This was a prospective cohort study of pregnant women undergoing cervical length screening assessment via transvaginal ultrasound examination at 18 to 22 weeks' gestation. A semiautomatic, cervical elastography application (E-Cervix) was used during the transvaginal examination to calculate 5 quantitative parameters (internal os stiffness, external os stiffness, internal -to -external os stiffness ratio, hardness ratio, and elasticity contrast index) and create a standard nomogram for each one of them. The intraobserver reliability was calculated using Shrout-Fleiss reliability. Cervical elastography parameters were compared between those who delivered preterm (<37 weeks) spontaneously and those who delivered full term. A multivariable logistic regression model was performed to determine the ability of the cervical elastography parameters to predict spontaneous preterm birth. RESULTS: A total of 742 women were included, of which 49 (6.6%) had a spontaneous preterm delivery. A standard nomogram was created for each of the cervical elastography parameters from those who had a full-term birth in the index pregnancy (n=693). Intraobserver reliability was good or excellent (intraclass correlation, 0.757-0.887) for each of the cervical elastography parameters except external os stiffness which was poor (intraclass correlation, 0.441). In univariate analysis, none of the cervical elastography parameters were associated with a statistically significant increased risk of spontaneous preterm birth. In a multivariable model adjusting for history of preterm birth, gravidity, ethnicity, cervical cerclage, and vaginal progesterone use, increasing elasticity contrast index was significantly associated with an increased risk of spontaneous preterm birth (odds ratio, 1.15; 95% confidence interval, 1.02-1.30; P=.02). CONCLUSION: Cervical elastography parameters are reliably measured and are stable across 18 to 22 weeks' gestation. Based on our findings, the elasticity contrast index was associated with an increased risk of spontaneous preterm birth and may be a useful parameter for future research.

Manufacture and mechanical properties of knee implants using SWCNTs/UHMWPE composites.

This article focuses on obtaining ultra high molecular weight polyethylene (UHMWPE) material reinforced with functionalized single-walled carbon nanotubes (f-SWCNTs) and the manufacturing of unicompartmental knee implants via Single-Point Incremental Forming process (SPIF). The physicochemical properties of the developed UHMWPE reinforced with 0.01 and 0.1 wt% concentrations of f-SWCNTs are investigated using Raman and Thermogravimetic Analysis (TGA). Tensile mechanical tests performed in the nanocomposite material samples reveal a 12% improvement in their Young's modulus when compare to that of the pure UHMWPE material samples. Furthermore, the surface biocompatibility of the UHMWPE reinforced with f-SWCNTs materials samples was evaluated with human osteoblast cells. Results show cell viability enhancement with good cell growth and differentiation after 14 incubation days, that validates the usefulness of the developed nanocomposite material in the production of hip and knee artificial implants, and other biomedical applications.

Antivirulence Activity of a Dietary Phytochemical: Hibiscus Acid Isolated from Hibiscus sabdariffa L. Reduces the Virulence of Pseudomonas aeruginosa in a Mouse Infection Model.

Hibiscus sabdariffa L. (Hs) calyxes, rich in organic acids, are included in diets in different countries. In recent years, some phytochemicals have been shown to reduce bacterial virulence at sublethal concentrations by interfering with quorum sensing (QS) systems. Therefore, in this study the antivirulence properties of Hs calyxes and two γ-lactones (hibiscus acid [HA] and its methyl ester) in Pseudomonas aeruginosa were analyzed. Acetone and methanol extracts of Hs showed anti-QS activity by inhibiting violacein production (60% to 80% with 250 µg/mL). In molecular docking analysis, the γ-lactones registered a good binding score, which suggests strong interaction with the active site of LasR protein. To verify their effect in vitro, they were isolated from Hs and evaluated in six QS-regulated phenotypes, as well as in ExoU toxin that is released by the type III secretion system (T3SS). At 500 µg/mL they reduced alkaline protease (29-52%) and elastase (15-37%) activity, biofilm formation (∼75%), and swarming (50%), but there was no effect on pyocyanin production, hemolytic activity, or type III secretion. In a mouse abscess/necrosis model, HA at sublethal concentrations (15 and 31.2 µg/mL) affected infection establishment and prevented damage and systemic spread. In conclusion, HA is the first molecule identified with antivirulence properties in Hs with the potential to prevent infections caused by P. aeruginosa.

Activation of ALDH1A1 by omeprazole reduces cell oxidative stress damage.

Under physiological conditions, cells produce low basal levels of reactive oxygen species (ROS); however, in pathologic conditions ROS production increases dramatically, generating high concentrations of toxic unsaturated aldehydes. Aldehyde dehydrogenases (ALDHs) are responsible for detoxification of these aldehydes protecting the cell. Due to the physiological relevance of these enzymes, it is important to design strategies to modulate their activity. It was previously reported that omeprazole activation of ALDH1A1 protected Escherichia coli cells overexpressing this enzyme, from oxidative stress generated by H2 O2 . In this work, omeprazole cell protection potential was evaluated in eukaryotic cells. AS-30D cell or hepatocyte suspensions were subjected to a treatment with omeprazole and exposure to light (that is required to activate omeprazole in the active site of ALDH) and then exposed to H2 O2 . Cells showed viability similar to control cells, total activity of ALDH was preserved, while cell levels of lipid aldehydes and oxidative stress markers were maintained low. Cell protection by omeprazole was avoided by inhibition of ALDHs with disulfiram, revealing the key role of these enzymes in the protection. Additionally, omeprazole also preserved ALDH2 (mitochondrial isoform) activity, diminishing lipid aldehyde levels and oxidative stress in this organelle, protecting mitochondrial respiration and transmembrane potential formation capacity, from the stress generated by H2 O2 . These results highlight the important role of ALDHs as part of the antioxidant system of the cell, since if the activity of these enzymes decreases under stress conditions, the viability of the cell is compromised.