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- ArticleThakur P, Bhalerao A.Cureus. 2023 Jun;15(6):e40423.Background Placenta-mediated complications, such as preeclampsia, placental abruption, and fetal growth restriction, can indeed lead to significant maternal and perinatal morbidity and mortality. Early detection and management of these conditions are crucial to ensuring optimal outcomes for both the mother and baby. However, there have been inconsistent correlations found between maternal homocysteine levels and placenta-related problems in various studies. Therefore, prospective research based on data pointing to a role for hyperhomocysteinemia in placenta-mediated complications will open doors for early detection and management of these complications. Thus, this study aims to determine if a higher risk of placenta-mediated problems is connected with a higher maternal plasma homocysteine content between 10 and 14 weeks of gestation. Methodology An observational prospective cohort study was conducted in the Department of Obstetrics and Gynecology, consisting of all the antenatal women between 10 and 14 weeks of gestation attending outpatient departments or inpatients admitted in labor rooms or wards having singleton pregnancies. Along with socio-demographic information and detailed history, a clinical examination was performed, and blood samples were collected to determine plasma homocysteine levels. Results As per the receiver operating characteristic curve (ROC curve), the cut-off value taken was <5 for the low level of serum homocysteine, 5 to 15 micromol/L for the normal value, and >15 micromol/L for a raised serum homocysteine level. The cutoff value for our study was 45 micromol/L with a sensitivity of 78.33%, a specificity of 91.67%, a positive predictive value of 90.38%, and a negative predictive value of 80.88% with a diagnostic accuracy of 85%. This means that, for most of the women included in the present study, those who developed placenta-mediated complications had serum blood homocysteine levels of 45 micromol/L or more at 10-14 weeks of gestation. Conclusion Women with high homocysteine levels in the late first trimester had more placenta-mediated complications, such as abruption, pre-eclampsia, restricted fetal growth, and recurrent pregnancy losses, compared to women with a normal level of homocysteine in the late first trimester. Therefore, measuring blood homocysteine levels in pregnancy may be helpful as a diagnostic test for the early detection of high-risk individuals for placenta-mediated complications.
- ArticleHo CT, Lin HH, Liou EJ, Lo LJ.Sci Rep. 2017 01 10;7:40423.Traditional planning method for orthognathic surgery has limitations of cephalometric analysis, especially for patients with asymmetry. The aim of this study was to assess surgical plan modification after 3-demensional (3D) simulation. The procedures were to perform traditional surgical planning, construction of 3D model for the initial surgical plan (P1), 3D model of altered surgical plan after simulation (P2), comparison between P1 and P2 models, surgical execution, and postoperative validation using superimposition and root-mean-square difference (RMSD) between postoperative 3D image and P2 simulation model. Surgical plan was modified after 3D simulation in 93% of the cases. Absolute linear changes of landmarks in mediolateral direction (x-axis) were significant and between 1.11 to 1.62 mm. The pitch, yaw, and roll rotation as well as ramus inclination correction also showed significant changes after the 3D planning. Yaw rotation of the maxillomandibular complex (1.88 ± 0.32°) and change of ramus inclination (3.37 ± 3.21°) were most frequently performed for correction of the facial asymmetry. Errors between the postsurgical image and 3D simulation were acceptable, with RMSD 0.63 ± 0.25 mm for the maxilla and 0.85 ± 0.41 mm for the mandible. The information from this study could be used to augment the clinical planning and surgical execution when a conventional approach is applied.
- ArticleEgerton T, Hinman RS, Hunter DJ, Bowden JL, Nicolson PJA, Atkins L, Pirotta M, Bennell KL.BMJ Open. 2020 10 07;10(10):e040423.OBJECTIVE: Implementation strategies, such as new models of service delivery, are needed to address evidence practice gaps. This paper describes the process of developing and operationalising a new model of service delivery to implement recommended care for people with knee osteoarthritis (OA) in a primary care setting.
METHODS: Three development stages occurred concurrently and iteratively. Each stage considered the healthcare context and was informed by stakeholder input. Stage 1 involved the design of a new model of service delivery (PARTNER). Stage 2 developed a behavioural change intervention targeting general practitioners (GPs) using the behavioural change wheel framework. In stage 3, the 'Care Support Team' component of the service delivery model was operationalised.
RESULTS: The focus of PARTNER is to provide patients with education, exercise and/or weight loss advice, and facilitate effective self-management through behavioural change support. Stage 1 model design: based on clinical practice guidelines, known evidence practice gaps in current care, chronic disease management frameworks, input from stakeholders and the opportunities and constraints afforded by the Australian primary care context, we developed the PARTNER service-delivery model. The key components are: (1) an effective GP consultation and (2) follow-up and ongoing care provided remotely (telephone/email/online resources) by a 'Care Support Team'. Stage 2 GP behavioural change intervention: a multimodal behavioural change intervention was developed comprising a self-audit/feedback activity, online professional development and desktop software to provide decision support, patient information resources and a referral mechanism to the 'Care Support Team'. Stage 3 operationalising the 'care support team'-staff recruited and trained in evidence-based knee OA management and behavioural change methodology.
CONCLUSION: The PARTNER model is the result of a comprehensive implementation strategy development process using evidence, behavioural change theory and intervention development guidelines. Technologies for scalable delivery were harnessed and new primary evidence was generated as part of the process.Trial registration number ACTRN12617001595303 (UTN U1111-1197-4809). - ArticleChen X, Mou K, Lu W, Schumacher L, Resende-De-Macedo N, Sitthicharoenchai P, Derscheid R, Burrough E, Li G.mSphere. 2023 Dec 20;8(6):e0040423.IMPORTANCE: This study highlights a Streptococcus equi subspecies zooepidemicus (S. zooepidemicus) strain isolated from an outbreak in Indiana, which resulted in mortality events among a swine herd in 2021. The Indiana outbreak strain was found to be genetically and phylogenetically distant to a strain isolated from the 2019 outbreaks in Ohio and Tennessee, which caused high swine mortality. We also discovered multiple unique genetic features in the Indiana outbreak strain, including distinct S. zooepidemicus genomic islands, and notable S. zooepidemicus virulence genes-many of which could serve as biomarkers for the diagnosis of this strain. These findings provide significant insights into monitoring and potentially preventing severe outbreaks caused by the Indiana outbreak strain in the future.
- ArticleNa G, Salt DE.J Biol Chem. 2011 Nov 25;286(47):40423-32.When growing in its native habitat, Thlaspi goesingense can hyperaccumulate 1.2% of its shoot dry weight as nickel. We reported previously that both constitutively elevated activity of serine acetyltransferase (SAT) and concentration of glutathione (GSH) are involved in the ability of T. goesingense to tolerate nickel. A feature of SAT is its feedback inhibition by L-cysteine. To understand the role of this regulation of SAT by Cys on GSH-mediated nickel tolerance in T. goesingense, we characterized the enzymatic properties of SATs from T. goesingense. We demonstrate that all three isoforms of SAT in T. goesingense are insensitive to inhibition by Cys. Further, two amino acids (proline and alanine) in the C-terminal region of the cytosolic SAT (SAT-c) from T. goesingense are responsible for converting the enzyme from a Cys-sensitive to a Cys-insensitive form. Furthermore, the Cys-insensitive isoform of SAT-c confers elevated resistance to nickel when expressed in Escherichia coli and Arabidopsis thaliana, supporting a role for altered regulation of SAT by Cys in nickel tolerance in T. goesingense.
- ArticleQin X, Zhang YA, Tu J.J Virol. 2023 05 31;97(5):e0040423.Phosphoprotein (P), co-factor of the polymerase (large protein, L) of single-stranded negative-sense RNA viruses, is phosphorylated during viral infection and its phosphorylation has been reported to play important roles in viral replication. However, the function of P phosphorylation in viral replication is still far from clear. Snakehead vesiculovirus (SHVV) is a kind of fish rhabdovirus that has caused serious economic losses in snakehead fish culture in China without any effective preventive or therapeutical measures currently. In this study, 4D label-free phosphoproteomics sequencing of SHVV-infected cells identified five phosphorylated sites on SHVV P, among which threonine 160 (T160) was proved to be phosphorylated. Overexpression of wild-type P, but not P-T160A or P-T160E mutant, promoted SHVV replication, suggesting that the T160 phosphorylation on the P protein is critical for SHVV replication. Moreover, we found that T160A or T160E mutation on SHVV P had no effect on the interactions of P-nucleoprotein (N), P-P, or P-L. Further study revealed that p38 mitogen-activated protein kinase (p38MAPK) and glycogen synthase kinase 3 (GSK3) interacted with SHVV P and mediated the T160 phosphorylation. Besides, overexpression of p38MAPK or GSK3 facilitated, while knockdown or activity inhibition of p38MAPK or GSK3 suppressed, SHVV replication. Overall, p38MAPK- and GSK3-mediated phosphorylation of the P protein at T160 is required for SHVV replication, which provided targets for designing anti-SHVV drugs and developing live-attenuated SHVV vaccines. Our study helps understand the role of P phosphorylation in the replication of single-stranded negative-sense RNA viruses. IMPORTANCE Phosphorylation of viral proteins plays important roles in viral replication. Currently, the role of phosphorylation of phosphoprotein (P) in the replication of single-stranded negative-sense RNA viruses is far from clear. Identification of the phosphorylated sites on viral P protein and the related host kinases is helpful for developing live-attenuated vaccines and designing antiviral drugs. This study focused on identifying the phosphorylated sites on P protein of a fish rhabdovirus SHVV, determining the related host kinases, and revealing the effects of the phosphorylated sites and kinases on SHVV replication. We found that SHVV P was phosphorylated at T160, which was mediated by the kinases p38MAPK and GSK3 to promote SHVV replication. This study is the first time to study the role of P phosphorylation in fish rhabdovirus replication.
- ArticleLau FH, Xia F, Kaplan A, Cerrato F, Greene AK, Taghinia A, Cowan CA, Labow BI.PLoS One. 2012;7(7):e40423.Macrodactyly is a rare family of congenital disorders characterized by the diffuse enlargement of 1 or more digits. Multiple tissue types within the affected digits are involved, but skeletal patterning and gross morphological features are preserved. Not all tissues are equally involved and there is marked heterogeneity with respect to clinical phenotype. The molecular mechanisms responsible for these growth disturbances offer unique insight into normal limb growth and development, in general. To date, no genes or loci have been implicated in the development of macrodactyly. In this study, we performed the first transcriptional profiling of macrodactyly tissue. We found that pleiotrophin (PTN) was significantly overexpressed across all our macrodactyly samples. The mitogenic functions of PTN correlate closely with the clinical characteristics of macrodactyly. PTN thus represents a promising target for further investigation into the etiology of overgrowth phenotypes.
- ArticleSit B, Lamason RL.J Bacteriol. 2024 02 22;206(2):e0040423.Our understanding of free-living bacterial models like Escherichia coli far outpaces that of obligate intracellular bacteria, which cannot be cultured axenically. All obligate intracellular bacteria are host-associated, and many cause serious human diseases. Their constant exposure to the distinct biochemical niche of the host has driven the evolution of numerous specialized bacteriological and genetic adaptations, as well as innovative molecular mechanisms of infection. Here, we review the history and use of pathogenic Rickettsia species, which cause an array of vector-borne vascular illnesses, as model systems to probe microbial biology. Although many challenges remain in our studies of these organisms, the rich pathogenic and biological diversity of Rickettsia spp. constitutes a unique backdrop to investigate how microbes survive and thrive in host and vector cells. We take a bacterial-focused perspective and highlight emerging insights that relate to new host-pathogen interactions, bacterial physiology, and evolution. The transformation of Rickettsia spp. from pathogens to models demonstrates how recalcitrant microbes may be leveraged in the lab to tap unmined bacterial diversity for new discoveries. Rickettsia spp. hold great promise as model systems not only to understand other obligate intracellular pathogens but also to discover new biology across and beyond bacteria.
- ArticleMoosavian M, Ahmadkhosravy N.Jundishapur J Microbiol. 2016 Nov;9(11):e40423.BACKGROUND: A common mechanism of resistance to beta-lactam antibiotics is the production of beta-lactamase by Gram-negative bacteria. Recently, nonderivative extended-spectrum beta-lactamases (ESBLs) from the TEM and SHV enzymes, such as CTX-M, that were related to different geographical regions have been recognized.
OBJECTIVES: The aim of this study was to determine the frequency of the CTX-M gene in ESBL-producing Enterobacteriaceae isolates in hospitalized patients in the teaching hospitals of Ahvaz, Iran.
METHODS: Enterobacteriaceae isolates from clinical specimens (other than stool), such as wounds, blood, urine, trachea, discharge, and abscess, were collected and examined. All the isolates were identified using standard biochemical tests. The combination test was carried out based on CLSI criteria for the phenotypic detection of ESBL-producing isolates. After DNA extraction, the CTX-M and CTX-M-1 genes were amplified using PCR among phenotypically positive ESBL isolates.
RESULTS: Among 240 Enterobacteriaceae isolates, Escherichia coli and Enterobacter were the most common isolates with 171 (71.3%) and 65 (27.1%), respectively. The combination test results also showed that 108 (45%) Enterobacteriaceae isolates were phenotypic ESBL producers, but 104 (96%) isolates were positive for the blaCTX-M gene and 99 (92%) were positive for the blaCTX-M-1 gene according to the PCR method.
CONCLUSIONS: The results of this study phenotypically and genotypically confirmed the high frequency of ESBL-producing strains, such as the CTX-M and CTX-M-1 genes, among Enterobacteriaceae isolates in our region. Therefore, use of antibiotic susceptibility testing for the detection of ESBL isolates prior to the prescription of beta-lactam antibiotics is recommended. This could help prevent the spread of bacteria strains that are resistant to beta-lactam antibiotics. - ArticleAnjum S, Anjum I, Hano C, Kousar S.RSC Adv. 2019 Dec 03;9(69):40404-40423.During the last few decades major advances have shed light on nanotechnology. Nanomaterials have been widely used in various fields such as medicine, energy, cosmetics, electronics, biotechnology and pharmaceuticals. Owing to their unique physicochemical characteristics and nanoscale structures, nanoparticles (NPs) have the capacity to enter into plant cells and interact with intracellular organelles and various metabolites. The effects of NPs on plant growth, development, physiology and biochemistry have been reported, but their impact on plant specialized metabolism (aka as secondary metabolism) still remains obscure. In reaction to environmental stress and elicitors, a common response in plants results in the production or activation of different types of specialized metabolites (e.g., alkaloids, terpenoids, phenolics and flavonoids). These plant specialized metabolites (SMs) are important for plant adaptation to an adverse environment, but also a huge number of them are biologically active and used in various commercially-valued products (pharmacy, cosmetic, agriculture, food/feed). Due to their wide array of applications, SMs have attracted much attention to explore and develop new strategies to enhance their production in plants. In this context, NPs emerged as a novel class of effective elicitors to enhance the production of various plant SMs. In recent years, many reports have been published regarding the elicitation of SMs by different types of NPs. However, in order to achieve an enhanced and sustainable production of these SMs, in-depth studies are required to figure out the most suitable NP in terms of type, size and/or effective concentration, along with a more complete understanding about their uptake, translocation, internalization and elicitation mechanisms. Herein, we are presenting a comprehensive and critical account of the plant SMs elicitation capacities of the three main classes of nanomaterials (i.e., metallic NPs (MNPs), metal oxide NPs (MONPs) and carbon related nanomaterials). Their different proposed uptake, translocation and internalization pathways as well as elicitation mechanism along with their possible deleterious effect on plant SMs and/or phytotoxic effects are summarized. We also identified and critically discussed the current research gaps existing in this field and requiring future investigation to further improve the use of these nanomaterials for an efficient production of plant SMs.
- ArticleAbdelhafez E, Dabbour L, Hamdan M.Environ Sci Pollut Res Int. 2021 Aug;28(30):40416-40423.This study aims to analyze the correlation between the daily confirmed COVID-19 cases in Jordan and metrological parameters including the average daily temperature (°C), maximum ambient temperature (°C), relative humidity (%), wind speed (m/s), pressure (kPa), and average daily solar radiation (W/m2). This covers the first and the second waves in Jordan. The data were obtained from both the Jordanian Ministry of health and the Jordan Metrological Department. In this work, the Spearman correlation test was used for data analysis, since the normality assumption was not fulfilled. It was found that the most effective weather parameters on the active cases of COVID-19 in the initial wave transmission was the average daily solar radiation (r = - 0.503; p = 0.000), while all other tests for other parameters failed. In the second wave of COVID-19 transmission, it was found that the most effective weather parameter on the active cases of COVID-19 was the maximum temperature (r = 0.394; p = 0.028). This was followed by wind speed (r = 0.477; p = 0.007), pressure (r = - 0.429; p = 0.016), and average daily solar radiation (r = - 0.757; p = 0.000). Furthermore, the independent variable importance of multilayer perceptron showed that wind speed has a direct relationship with active cases. Conversely, areas characterized by low values of pressure and daily solar radiation exposure have a high rate of infection. Finally, a global sensitivity analysis using Sobol analysis showed that daily solar radiation has a high rate of active cases that support the virus' survival in both wave transmissions.
- ArticleWei R, Tian X, Luo H, Liu M, Yang Z, Luo Z, Zhu H, Guo H, Li J, Qiu J.ACS Appl Mater Interfaces. 2019 Oct 30;11(43):40416-40423.Heavily self-doped semiconductors can be designed to be used in advanced photonics due to both fabrication and functional advantages. Ultrafast response, strong optical nonlinearity, broadband wavelength range, and accessibility of integration are major challenges for ultrafast all-optical photonics to operate in the infrared wavelength range. Here, solution-processed Cu1.8Se semiconductor nanocrystals (NCs) demonstrate an ultrafast response (about 360-520 fs), strong optical nonlinearity (as large as -1.4 × 103 cm GW-1), and broadband (from 800 to 3000 nm) nonlinear optical absorption in the near-infrared and mid-infrared wavelength ranges. The ultrafast response and larger optical nonlinearity may be triggered by the plasma ground-state bleaching in the strong surface electromagnetic filed. Stable Q-switched lasers in Er-doped fiber laser, Tm-doped fiber laser, and Ho/Pr-codoped ZBLAN fiber laser are operated, respectively. These findings indicate that Cu1.8Se NCs are prospective nonlinear materials for ultrafast response and broadband pulse laser.
- Articleda Silva Souza ID, Berkowitz E, Chea JD, McBride N, Sweet K, Torri D, Burgo RV, Savelski MJ, Stanzione JF.ACS Appl Mater Interfaces. 2018 Nov 28;10(47):40411-40423.Sun protection is a global concern, and maximizing sunscreen stability and efficacy depends partially on the prevention of UV filters recrystallization. We aimed to study the efficacy of hydrophobic solubilizers in preventing the recrystallization of solid hydrophobic UV filters in predissolutions, sunscreen formulations, and during simulated human use. Recrystallization of UV filters induced by ultrasonication, temperature variation, or simulated human application was analyzed by different methods. Maximum solubility of UV filters in solubilizers was determined. Surprisingly, the best solubilizer was not necessarily the best solvent to prevent recrystallization, suggesting there are different forces controlling these phenomena. Hydrophobic solubilizers tend to perform better than ethanol in predissolutions, but the presence of other components in final products may change their performance. Results suggest that some UV filters tend to form liquid clusters, which may behave as crystals and affect the desired even distribution of UV filters on the skin. UV filters were also found to respond differently to Hansen Solubility Parameters. Scanning electron microscopy supports the fact that recrystallization upon sunscreen application is an issue to be tested during development. A timesaving method to predict recrystallization of UV filters in clear systems was developed and is presented as a tool to enhance the efficacy of sunscreens.
- ArticleWang X, Yeh S, Wu G, Hsu CL, Wang L, Chiang T, Yang Y, Guo Y, Chang C.J Biol Chem. 2001 Nov 02;276(44):40417-23.The androgen receptor (AR) is a member of the steroid receptor superfamily that binds to the androgen response element to regulate target gene transcription. AR may need to interact with some selected coregulators for maximal or proper androgen function. Here we report the isolation of a new AR coregulator with a calculated molecular mass of 267 kDa named the androgen receptor-associated protein 267-alpha (ARA267-alpha). ARA267-alpha contains 2427 amino acids, including one Su(var)3-9, Enhancer-of-zeste, and Trithorax (SET) domain, two LXXLL motifs, three nuclear translocation signal (NLS) sequences, and four plant homeodomain (PHD) finger domains. Northern blot analyses reveal that ARA267-alpha is expressed predominantly in the lymph node as 13- and 10-kilobase transcripts. HepG2 is the only cell line tested that does not express ARA267-alpha. Yeast two-hybrid and glutathione S-transferase pull-down assays show that both the N and C terminus of ARA267-alpha interact with the AR DNA- and ligand-binding domains. Unlike other coregulators, such as CBP, which enhance the interaction between the N and C terminus of AR, we found that ARA267-alpha had little influence on the interaction between the N and C terminus of AR. Luciferase and chloramphenicol acetyltransferase assays show that ARA267-alpha can enhance AR transactivation in a dihydrotestosterone-dependent manner in PC-3 and H1299 cells. ARA267-alpha can also enhance AR transactivation with other coregulators, such as ARA24 or PCAF, a histone acetylase, in an additive manner. Together, our data demonstrate that ARA267-alpha is a new AR coregulator containing the SET domain with an exceptionally large molecular mass that can enhance AR transactivation in prostate cancer cells.