Prediction by uterine artery Doppler screening of small-for-gestational-age neonates at 19-24 weeks' gestation.

OBJECTIVE: Small-for-gestational-age (SGA) neonates are at increased risk of perinatal mortality and morbidity. We aimed to investigate the performance of uterine artery pulsatility index (UtA-PI) at 19-24 weeks' gestation to predict the delivery of a SGA neonate in a Chinese population. METHODS: This was a retrospective cohort study using data obtained between January 2010 and June 2018. Doppler ultrasonography was performed at 19-24 weeks' gestation. SGA was defined as birth weight below the 10th centile according to the INTERGROWTH-21st fetal growth standards. The performance of UtA-PI to predict the delivery of a SGA neonate was assessed using receiver-operating-characteristics (ROC)-curve analysis. RESULTS: We included 6964 singleton pregnancies, of which 748 (11%) delivered a SGA neonate, including 115 (15%) women with preterm delivery. Increased UtA-PI was associated with an elevated risk of SGA, both in neonates delivered at or after 37 weeks' gestation (term SGA) and those delivered before 37 weeks (preterm SGA). The areas under the ROC curve (AUCs) for UtA-PI were 64.4% (95% CI, 61.5-67.3%) and 75.8% (95% CI, 69.3-82.3%) for term and preterm SGA, respectively. The performance of combined screening by maternal demographic/clinical characteristics and estimated fetal weight in the detection of term and preterm SGA was improved significantly by the addition of UtA-PI, although the increase in AUC was modest (2.4% for term SGA and 4.9% for preterm SGA). CONCLUSIONS: This is the first Chinese study to evaluate the role of UtA-PI at 19-24 weeks' gestation in the prediction of the delivery of a neonate with SGA. The addition of UtA-PI to traditional risk factors improved the screening performance for SGA, and this improvement was greater in predicting preterm SGA compared with term SGA. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

[Effect of non-breathing-related sleep fragmentation on cognitive function in patients with cerebral small vessel disease].

Objective: To investigate the effect of non-breathing-related sleep fragmentation on cognitive function in patients with atherosclerotic cerebral small vessel disease(CSVD). Methods: Seventy-two patients with arteriosclerotic CSVD in the Department of Neurology, the Third Affiliated Hospital of Sun Yat-sen University were enrolled in this study from August 2017 to July 2018. The patients undertook MRA(Magnetic Resonance Angiography)+SWI(Susceptibility weighted imaging), polysomnography, Montreal Cognitive Inventory (MoCA) and Concise Mental State Examination (MMSE). The patients were divided into study group (≥19) and control group (<19) according to the median number of arousal events (median=19) at night. Results: The sleep efficiency, rapid eye movement (REM) sleep ratio and non-rapid eye movement-3 (NREM-3) sleep ratio of the study group were significantly lower than those of the control group (P<0.05), and the total MoCA score (18.2±4.3) , visual space score(1.9±1.4) and delayed recall score(1.4±0.9) of the study group were significantly lower than those of the control group (22.7±3.5, 2.9±1.2, 2.9±1.1, P<0.05). Conclusion: The incidence of non-breathing-related sleep fragmentation is high in CSVD patients and this kind of fragmentation is associated with cognitive impairment.

Rapid Microbiology Screening in Pharmaceutical Workflows.

Recently advances in miniaturization and automation have been utilized to rapidly decrease the time to result for microbiology testing in the clinic. These advances have been made due to the limitations of conventional culture-based microbiology methods, including agar plate and microbroth dilution, which have long turnaround times and require physicians to treat patients empirically with antibiotics before test results are available. Currently, there exist similar limitations in pharmaceutical sterility and bioburden testing, where the long turnaround times associated with standard microbiology testing drive costly inefficiencies in workflows. These include the time lag associated with sterility screening within drug production lines and the warehousing cost and time delays within supply chains during product testing. Herein, we demonstrate a proof-of-concept combination of a rapid microfluidic assay and an efficient cell filtration process that enables a path toward integrating rapid tests directly into pharmaceutical microbiological screening workflows. We demonstrate separation and detection of Escherichia coli directly captured and analyzed from a mammalian (i.e., CHO) cell culture with a 3.0 h incubation. The demonstration is performed using a membrane filtration module that is compatible with sampling from bioreactors, enabling in-line sampling and process monitoring.

Down-regulation of miR-342-3p in hepatocellular carcinoma tissues and its prognostic significance.

OBJECTIVE: The involvement of microRNAs in cancer and their potential as biomarkers of prognosis are becoming increasingly appreciated. The aim of this study was to evaluate the clinical importance and prognostic value of miR-342-3p in hepatocellular carcinoma (HCC). PATIENTS AND METHODS: RT-PCR was used to detect the expression of miR-342-3p. The association with clinicopathologic features was analyzed. Kaplan-Meier survival analysis and Cox proportional hazards analysis were used to compare the overall survival between HCC patients with high miR-342-3p expression and those with low miR-342-3p expression. RESULTS: We found that miR-342-3p expression was significantly decreased in HCC tissues compared with paired adjacent non-tumor tissues (p < 0.001). MiR-342-3p expression was correlated with histologic grade (p = 0.008) and tumor TNM stage (p = 0.001). Kaplan-Meier survival analysis showed that patients in the high miR-342-3p expression group had better overall survival than those in the low miR-342-3p expression group (p < 0.001). Univariate analysis showed that miR-342-3p (p = 0.001), TNM stage (p = 0.002) and histologic grade (p = 0.006) were associated with poor survival rates. Multivariate analysis confirmed that miR-342-3p expression can be used as an independent predictor for HCC prognosis (p = 0.002). CONCLUSIONS: miR-342-3p may serve as a tumor suppressor during HCC progression, and its low expression may be a potential biomarker for poor prognosis of HCC.

Fish optimize sensing and respiration during undulatory swimming.

Previous work in fishes considers undulation as a means of propulsion without addressing how it may affect other functions such as sensing and respiration. Here we show that undulation can optimize propulsion, flow sensing and respiration concurrently without any apparent tradeoffs when head movements are coupled correctly with the movements of the body. This finding challenges a long-held assumption that head movements are simply an unintended consequence of undulation, existing only because of the recoil of an oscillating tail. We use a combination of theoretical, biological and physical experiments to reveal the hydrodynamic mechanisms underlying this concerted optimization. Based on our results we develop a parsimonious control architecture that can be used by both undulatory animals and machines in dynamic environments.

Identification and reproducibility of diagnostic DNA markers for tuber starch and yield optimization in a novel association mapping population of potato (Solanum tuberosum L.).

KEY MESSAGE: SNPs in candidate genes Pain - 1, InvCD141 (invertases), SSIV (starch synthase), StCDF1 (transcription factor), LapN (leucine aminopeptidase), and cytoplasm type are associated with potato tuber yield, starch content and/or starch yield. Tuber yield (TY), starch content (TSC), and starch yield (TSY) are complex characters of high importance for the potato crop in general and for industrial starch production in particular. DNA markers associated with superior alleles of genes that control the natural variation of TY, TSC, and TSY could increase precision and speed of breeding new cultivars optimized for potato starch production. Diagnostic DNA markers are identified by association mapping in populations of tetraploid potato varieties and advanced breeding clones. A novel association mapping population of 282 genotypes including varieties, breeding clones and Andean landraces was assembled and field evaluated in Northern Spain for TY, TSC, TSY, tuber number (TN) and tuber weight (TW). The landraces had lower mean values of TY, TW, TN, and TSY. The population was genotyped for 183 microsatellite alleles, 221 single nucleotide polymorphisms (SNPs) in fourteen candidate genes and eight known diagnostic markers for TSC and TSY. Association test statistics including kinship and population structure reproduced five known marker-trait associations of candidate genes and discovered new ones, particularly for tuber yield and starch yield. The inclusion of landraces increased the number of detected marker-trait associations. Integration of the present association mapping results with previous QTL linkage mapping studies for TY, TSC, TSY, TW, TN, and tuberization revealed some hot spots of QTL for these traits in the potato genome. The genomic positions of markers linked or associated with QTL for complex tuber traits suggest high multiplicity and genome wide distribution of the underlying genes.

Retinoblastoma protein-interacting zinc-finger gene 1 (RIZ1) dysregulation in human malignant meningiomas.

Retinoblastoma protein-interacting zinc-finger gene 1 (RIZ1) expression is often silenced in many types of human tumors. However, the relationship between RIZ1 expression and malignant meningiomas remains unclear. Here we have found for the first time that the expression of RIZ1 genes are associated with meningiomas progression through extensive analyses of Affymetrix GeneChip microarray data. Further validation methods for gene expression included quantitative PCR (qPCR), western blot and immunohistochemistry analysis, and these methods confirmed that RIZ1 is significantly downregulated in malignant meningioma tissues, as compared with benign meningiomas. In addition, malignant meningioma cells were stably transfected with ectogenic RIZ1 using Lentivirus-mediated transfection, and the transfections were followed by an in vitro 5-bromo-2-deoxyuridin incorporation assay, colony formation assay, cell cycle analysis, invasive analysis, apoptotic assay and western blot analysis. Our results demonstrate that the forced expression of RIZ1 in a malignant meningioma cell line inhibited cellular proliferation and arrested the cells in the G2/M phase of the cell cycle. We also confirmed that overexpression of RIZ1 may induce apoptosis of malignant meningioma cells. Furthermore, RIZ1 overexpression in malignant meningioma cells was associated with the downregulation of c-myc expression. These results from our study indicate that RIZ1 expression is significantly downregulated as the formation of meningiomas progressed, and suggest that RIZ1 may represent a promising candidate tumor suppressor gene that contributes to malignant meningiomas.

Foot pressure and center of pressure in athletes with ankle instability during lateral shuffling and running gait.

This study evaluates foot pressure and center of pressure (COP) patterns in individuals with ankle instability during running and lateral shuffling. Eleven participants with ankle instability (AI) and 11 normal subjects (Normal) performed running and lateral shuffling tasks. The outcome measures were foot progression angle, peak pressure, and displacement of COP during stance phase. During running, the foot progression angle, that is, the angle of foot abduction, was lower in the AI group (Normal: 13.46° ± 4.45°; AI: 8.78° ± 3.91°), and the 1st metatarsal contact pressure (Normal: 0.76 ± 0.47 N/cm(2)·kg; AI: 1.05 ± 0.70 N/cm(2)·kg) and the 3rd metatarsal peak pressure were higher in the AI (Normal: 0.96 ± 0.60 N/cm(2)·kg; AI: 1.54 ± 0.68 N/cm(2)·kg). The medial-lateral (M-L) COP in the late-stance phase of running for the AI group transferred faster from lateral to medial foot than the Normal group. For lateral shuffling, the AI group had greater peak pressure at the 1st (Normal: 0.76 ± 0.67 N/cm(2)·kg; AI: 1.49 ± 1.04 N/cm(2)·kg), 2nd (Normal: 0.57 ± 0.39 N/cm(2)·kg; AI: 0.87 ± 0.68 N/cm(2)·kg), 3rd (Normal: 0.70 ± 0.54 N/cm(2)·kg; AI: 1.42 ± 0.87 N/cm(2)·kg), and 4th (Normal: 0.52 ± 0.38 N/cm(2)·kg; AI: 1.12 ± 0.78 N/cm(2)·kg) metatarsal areas than the Normal group. The M-L COP located more laterally from the early to mid-stance phase in the AI compared with the Normal group. The findings suggest that COP displacement during lateral shuffle may be a factor in ankle instability while the foot progression angle during running may be a compensatory strategy.

Rapid detection of urinary tract infections using isotachophoresis and molecular beacons.

We present a novel assay for rapid detection and identification of bacterial urinary tract infections using isotachophoresis (ITP) and molecular beacons. We applied on-chip ITP to extract and focus 16S rRNA directly from bacterial lysate and used molecular beacons to achieve detection of bacteria specific sequences. We demonstrated detection of E. coli in bacteria cultures as well as in patient urine samples in the clinically relevant range 1E6-1E8 cfu/mL. For bacterial cultures we further demonstrate quantification in this range. The assay requires minimal sample preparation (a single centrifugation and dilution), and can be completed, from beginning of lysing to detection, in under 15 min. We believe that the principles presented here can be used for design of other rapid diagnostics or detection methods for pathogenic diseases.

A synthetic iterative pathway for ketoacid elongation.

Iterative formation of nonpolymeric carbon-carbon bonds has been employed by organisms to synthesize fatty acids, polyketides, and isoprenoids. In these biosynthetic schemes, same reaction cycles are used iteratively for functional modifications that result in the increase in carbon-chain length. This principle has been used in the design of a synthetic module for 2-ketoacid elongation. The system utilizes the Escherichia coli enzymes LeuABCD, which were engineered to accept bulkier nonnatural substrates, and was able to extend the chain length iteratively. The success in achieving a diverse range of 2-ketoacids and alcohols from this module via engineering of the 2-isopropylmalate synthase and ketoacid decarboxylase demonstrates the plasticity of LeuABCD and its feasibility for iterative carbon-chain elongations. In addition, this strategy illustrates a principle of designing novel metabolic modules for nonpolymeric carbon-chain elongation, which is essential in the synthesis of nonnative metabolites in microorganisms.

Management of odontogenic orbital cellulitis.

This work describes a series of patients with odontogenic orbital cellulitis (OOC), focusing on rate of abscess formation, need for surgical intervention, and imaging findings helpful for rapid diagnosis. Review of a current case and 22 patients with OOC from the scientific literature demonstrated periapical lucency as the most commonly (36.4%) reported finding on facial and orbital computerized tomography (CT) scan. Orbital abscess occurred in 72.7% of cases, and tooth extraction and/or abscess drainage was required in 95.5% of cases reviewed for control of infection. The current case presented with periapical lucency on CT scan, developed orbital abscess despite broad spectrum antibiotic therapy, and required multiple surgical interventions for disease resolution. Though our patient regained excellent vision, OOC often can result in severe vision loss. Periapical lucency on CT can help identify this atypical origin of cellulitis that is strongly associated with abscess formation and need for surgical intervention.

Metabolic engineering of Escherichia coli for 1-butanol and 1-propanol production via the keto-acid pathways.

Production of higher alcohols via the keto-acid intermediates found in microorganism's native amino-acid pathways has recently shown promising results. In this work, an Escherichia coli strain that produces 1-butanol and 1-propanol from glucose was constructed. The strain first converts glucose to 2-ketobutyrate, a common keto-acid intermediate for isoleucine biosynthesis. Then, 2-ketobutyrate is converted to 1-propanol through reactions catalyzed by the heterologous decarboxylase and dehydrogenase, or to 1-butanol via the chemistry involved in the synthesis of the unnatural amino acid norvaline. We systematically improved the synthesis of 1-propanol and 1-butanol through deregulation of amino-acid biosynthesis and elimination of competing pathways. The final strain demonstrated a production titer of 2 g/L with nearly 1:1 ratio of butanol and propanol.

Engineered synthetic pathway for isopropanol production in Escherichia coli.

A synthetic pathway was engineered in Escherichia coli to produce isopropanol by expressing various combinations of genes from Clostridium acetobutylicum ATCC 824, E. coli K-12 MG1655, Clostridium beijerinckii NRRL B593, and Thermoanaerobacter brockii HTD4. The strain with the combination of C. acetobutylicum thl (acetyl-coenzyme A [CoA] acetyltransferase), E. coli atoAD (acetoacetyl-CoA transferase), C. acetobutylicum adc (acetoacetate decarboxylase), and C. beijerinckii adh (secondary alcohol dehydrogenase) achieved the highest titer. This strain produced 81.6 mM isopropanol in shake flasks with a yield of 43.5% (mol/mol) in the production phase. To our knowledge, this work is the first to produce isopropanol in E. coli, and the titer exceeded that from the native producers.

The design of intracellular oscillators that interact with metabolism.

Biological oscillations such as circadian rhythms are ubiquitous in nature and have attracted significant attention because of their intriguing dynamics and important biological roles. Understanding of such sophisticated and robust oscillators requires more than the traditional reductionist approach. Recently, a synthetic approach similar to the design of engineering machinery has provided a valuable alternative for testing hypothetical operating principles. These man-made genetic circuits and gene-metabolic circuits are designed based on physical concepts, guided by mathematical models, and constrained by biological and chemical reality. While still primitive compared with the natural circuits, the designed gene-metabolic oscillator has begun to show hallmarks of circadian rhythms such as temperature compensation and close interaction with metabolism.

Transcriptional regulation and metabolism.

Understanding organisms from a systems perspective is essential for predicting cellular behaviour as well as designing gene-metabolic circuits for novel functions. The structure, dynamics and interactions of cellular networks are all vital components of systems biology. To facilitate investigation of these aspects, we have developed an integrative technique called network component analysis, which utilizes mRNA expression and transcriptional network connectivity to determine network component dynamics, functions and interactions. This approach has been applied to elucidate transcription factor dynamics in Saccharomyces cerevisiae cell-cycle regulation, detect cross-talks in Escherichia coli two-component signalling pathways, and characterize E. coli carbon source transition. An ultimate test of system-wide understanding is the ability to design and construct novel gene-metabolic circuits. To this end, artificial feedback regulation, cell-cell communication and oscillatory circuits have been constructed, which demonstrate the design principles of gene-metabolic regulation in the cell.

Acetate-inducible protein overexpression from the glnAp2 promoter of Escherichia coli.

The Ntr regulon in Escherichia coli has previously been engineered to control the expression of a heterologous metabolic pathway. In this study, we reengineered the same system for protein production. In the absence of NRII (glnL gene product), we showed that glnAp2 can be an effective promoter for protein production that is inducible by exogenous acetate, but both the induction ratio and the range of modulation are low. To deal with this issue, we inactivated phosphotransacetylase (pta gene product), which disrupts the acetate pathway and denies the cell the ability to synthesize acetate. With this additional modification, gene expression from glnAp2 can be controlled by directly adding acetate into the growth medium. Using a lacZ reporter fusion, we found that glnAp2 induction was modulatable over a range of potassium acetate concentrations, and the induction/noninduction ratio increased to 77 in the absence of pta. The extracellular acetate required for maximal induction is lower than the concentration that causes toxicity, and thus growth inhibition by acetate addition was not a matter of concern. Furthermore, compared to the P(tac) promoter, overexpression of a model protein using the modified glnAp2 promoter system did not cause significant growth inhibition, although a higher level of protein expression was achieved.

Pediatric urine testing.

Today, urinalysis is one of the most common clinical tests ordered for adult and pediatric patients. Because urine specimens are usually readily available and are obtained noninvasively, the urine testing is well suited for children. This article discusses the most common urine tests performed in children for screening purposes and also less common tests for diagnosis of specific disorders. Special considerations regarding urine specimen collection in children are discussed. Some simple tests that are underused by clinicians are mentioned, as are some exciting new molecular applications of urine testing.

Neonatal circumcision.

The merits of neonatal circumcision continue to be debated hotly. Some argue that circumcision is a "uniquely American medical enigma." Most of the world's male population remains uncircumcised; however, most boys born in the United States continue to undergo neonatal circumcision. Review of existing literature supports that most children who are uncircumcised do well from a medical standpoint and, thus, the question of whether US health care practitioners are subjecting neonates to an unnecessary surgical procedure remains. The medical benefits of circumcision are multiple, but most are small. The clearest medical benefit of circumcision is the relative reduction in the risk for a UTI, especially in early infancy. Although this risk [figure: see text] is real, the absolute numbers are small (risk ranges from 1 in 100 to 1 in 1000), and one investigator has estimated that it may take approximately 80 neonatal circumcisions to prevent one UTI. In the case of a patient with known urologic abnormalities that predispose to UTI, neonatal circumcision has a clearer role in terms of medical benefit to the patient. Most of the other medical benefits of circumcision probably can be realized without circumcision as long as access to clean water and proper penile hygiene are achieved. Proper penile hygiene should all but eliminate the risk for foreskin-related medical problems that will require circumcision. Moreover, proper hygiene and access to clean water has been shown to reduce the rate of development of squamous cell carcinoma of the penis in the uncircumcised population. Proper techniques on the care of the foreskin are illustrated in the American Academy of Pediatrics pamphlet titled "How to care for the uncircumcised penis." Regarding the relationship between STDs and circumcision, patient education and the practice of low-risk sexual behavior make a far greater impact than does routine circumcision in hopes of reducing the spread of HIV and other STDs. Nevertheless, in areas where safe sexual practices are poorly adhered to, circumcision can have a relative protective effect against the transmission of HIV and other STDs. The medical harms of circumcision lie mainly in the 1% acute complication rate and the additional patients who require revision of their initial circumcision for cosmetic or medical reasons. Anecdotally, the authors see far fewer complications in the acute and long-term phase when the circumcision has been performed by someone with expertise and experience with the procedure. Thus, the authors routinely recommend to parents that, if they choose to have their newborns circumcised, they should seek out an experienced practitioner. A negative psychologic and sexual impact of circumcision has been argued, but solid, scientific data are lacking. Special interest groups have argued that perhaps the greatest harm of circumcision is in performing an operation without a clear indication. Many of these groups have claimed that performing a routine neonatal circumcision is akin to performing a surgical procedure without a clear medical benefit, and in an infant, that is akin to surgery without informed consent. Although this is an extreme posture, the clinician can understand the emphasis on trying to provide invasive medical services only when a clear medical benefit is expected, especially when treating an infant or child. Deciding whether or not to circumcise an infant continues to challenge many new parents. Clearly, the procedure provides potential medical benefits and potential risks. It is difficult to say whether the benefits outweigh the risks for all male infants. Further complicating the decision for many American parents is that, in some areas of the United States, there exists an unexplained positive cultural connotation with neonatal circumcision. For these reasons, parents who actively choose to keep their sons uncircumcised need to be encouraged to make this decision forthrightly. Parents who choose to have their children circumcised also should be encouraged to actively seek an experienced practitioner who can afford the child adequate local analgesia.

Modulation of nitric oxide bioavailability by erythrocytes.

Nitric oxide (NO) activates soluble guanylyl cyclase in smooth muscle cells to induce vasodilation in the vasculature. However, as hemoglobin (Hb) is an effective scavenger of NO and is present in high concentrations inside the red blood cell (RBC), the bioavailability of NO would be too low to elicit soluble guanylyl cyclase activation in the presence of blood. Therefore, NO bioactivity must be preserved. Here we present evidence suggesting that the RBC participates in the preservation of NO bioactivity by reducing NO influx. The NO uptake by RBCs was increased and decreased by altering the degree of band 3 binding to the cytoskeleton. Methemoglobin and denatured hemoglobin binding to the RBC membrane or cytoskeleton also were shown to contribute to reducing the NO uptake rate of the RBC. These alterations in NO uptake by the RBC, hence the NO bioavailability, were determined to correlate with the vasodilation of isolated blood vessels. Our observations suggest that RBC membrane and cytoskeleton associated NO-inert proteins provide a barrier for NO diffusion and thus account for the reduction in the NO uptake rate of RBCs.