The stability of 65 biochemistry analytes in plasma, serum, and whole blood.

OBJECTIVES: The pre-analytical stability of various biochemical analytes requires careful consideration, as it can lead to the release of erroneous laboratory results. There is currently significant variability in the literature regarding the pre-analytical stability of various analytes. The aim of this study was to determine the pre-analytical stability of 65 analytes in whole blood, serum and plasma using a standardized approach. METHODS: Blood samples were collected from 30 healthy volunteers (10 volunteers per analyte) into five vacutainers; either SST, Li-heparin, K2-EDTA, or Na-fluoride/K-oxalate. Several conditions were tested, including delayed centrifugation with storage of whole blood at room temperature (RT) for 8 h, delayed centrifugation with storage of whole blood at RT or 4 °C for 24 h, and immediate centrifugation with storage of plasma or serum at RT for 24 h. Percent deviation (% PD) from baseline was calculated for each analyte and compared to the maximum permissible instability (MPI) derived from intra- and inter-individual biological variation. RESULTS: The majority of the analytes evaluated remained stable across all vacutainer types, temperatures, and timepoints tested. Glucose, potassium, and aspartate aminotransferase, among others, were significantly impacted by delayed centrifugation, having been found to be unstable in whole blood specimens stored at room temperature for 8 h. CONCLUSIONS: The data presented provides insight into the pre-analytical variables that impact the stability of routine biochemical analytes. This study may help to reduce the frequency of erroneous laboratory results released due to exceeded stability and reduce unnecessary repeat phlebotomy for analytes that remain stable despite delayed processing.

Polypharmacy in Multiple Sclerosis: Current Knowledge and Future Directions.

Polypharmacy, or the daily use of five or more medications, is well documented in older adults and linked to negative outcomes such as medication errors, adverse drug reactions, and increased healthcare utilization. Like older adults, people with multiple sclerosis (PwMS) are susceptible to polypharmacy, owing to the variety of treatments used to address individual multiple sclerosis (MS) symptoms and other comorbidities. Between 15-65% of PwMS meet criteria for polypharmacy; in this population, polypharmacy is associated with increased reports of fatigue, subjective cognitive impairment, and reduced quality of life. Despite evidence of adverse outcomes, polypharmacy among PwMS remains a neglected area of research. This article examines the current literature regarding polypharmacy in MS, as well as implications for clinical practice and directions for future research.

Automated Quantification of Hydroxyl Reactivities: Prediction of Glycosylation Reactions.

The stereoselectivity and yield in glycosylation reactions are paramount but unpredictable. We have developed a database of acceptor nucleophilic constants (Aka) to quantify the nucleophilicity of hydroxyl groups in glycosylation influenced by the steric, electronic and structural effects, providing a connection between experiments and computer algorithms. The subtle reactivity differences among the hydroxyl groups on various carbohydrate molecules can be defined by Aka, which is easily accessible by a simple and convenient automation system to assure high reproducibility and accuracy. A diverse range of glycosylation donors and acceptors with well-defined reactivity and promoters were organized and processed by the designed software program "GlycoComputer" for prediction of glycosylation reactions without involving sophisticated computational processing. The importance of Aka was further verified by random forest algorithm, and the applicability was tested by the synthesis of a Lewis A skeleton to show that the stereoselectivity and yield can be accurately estimated.

Speaker gaze increases information coupling between infant and adult brains.

When infants and adults communicate, they exchange social signals of availability and communicative intention such as eye gaze. Previous research indicates that when communication is successful, close temporal dependencies arise between adult speakers' and listeners' neural activity. However, it is not known whether similar neural contingencies exist within adult-infant dyads. Here, we used dual-electroencephalography to assess whether direct gaze increases neural coupling between adults and infants during screen-based and live interactions. In experiment 1 (n = 17), infants viewed videos of an adult who was singing nursery rhymes with (i) direct gaze (looking forward), (ii) indirect gaze (head and eyes averted by 20°), or (iii) direct-oblique gaze (head averted but eyes orientated forward). In experiment 2 (n = 19), infants viewed the same adult in a live context, singing with direct or indirect gaze. Gaze-related changes in adult-infant neural network connectivity were measured using partial directed coherence. Across both experiments, the adult had a significant (Granger) causal influence on infants' neural activity, which was stronger during direct and direct-oblique gaze relative to indirect gaze. During live interactions, infants also influenced the adult more during direct than indirect gaze. Further, infants vocalized more frequently during live direct gaze, and individual infants who vocalized longer also elicited stronger synchronization from the adult. These results demonstrate that direct gaze strengthens bidirectional adult-infant neural connectivity during communication. Thus, ostensive social signals could act to bring brains into mutual temporal alignment, creating a joint-networked state that is structured to facilitate information transfer during early communication and learning.

Direct Dehydrative Glycosylation Catalyzed by Diphenylammonium Triflate.

Methods for direct dehydrative glycosylations of carbohydrate hemiacetals catalyzed by diphenylammonium triflate under microwave irradiation are described. Both armed and disarmed glycosyl-C1-hemiacetal donors were efficiently glycosylated in moderate to excellent yields without the need for any drying agents and stoichiometric additives. This method has been successfully applied to a solid-phase glycosylation.

Establishment of Guidelines for the Control of Glycosylation Reactions and Intermediates by Quantitative Assessment of Reactivity.

Stereocontrolled chemical glycosylation remains a major challenge despite vast efforts reported over many decades and so far still mainly relies on trial and error. Now it is shown that the relative reactivity value (RRV) of thioglycosides is an indicator for revealing stereoselectivities according to four types of acceptors. Mechanistic studies show that the reaction is dominated by two distinct intermediates: glycosyl triflates and glycosyl halides from N-halosuccinimide (NXS)/TfOH. The formation of glycosyl halide is highly correlated with the production of α-glycoside. These findings enable glycosylation reactions to be foreseen by using RRVs as an α/ß-selectivity indicator and guidelines and rules to be developed for stereocontrolled glycosylation.

Persistence of fimbrial tissue on the ovarian surface after salpingectomy.

BACKGROUND: Salpingectomy is recommended as a risk-reducing strategy for epithelial tubo-ovarian cancer. The gold standard procedure is complete tubal excision. OBJECTIVE: The purpose of this study was to assess the presence of residual fimbrial/tubal tissue on ovarian surfaces after salpingectomy. STUDY DESIGN: Prospective analysis of patients who underwent salpingo-oophorectomy with or without hysterectomy for benign indications, early cervical cancer, or low-risk endometrial cancer at a UK National Health Service Trust. Salpingectomy with or without hysterectomy was performed initially, followed by oophorectomy within the same operation. Separately retrieved tubes and ovaries were sectioned serially and examined completely histologically. The main outcome measure was histologically identified fimbrial/ tubal tissue on ovarian surface. Chi-square/Fisher's exact tests were used to evaluate categoric variables. RESULTS: Twenty-five consecutive cases (mean age, 54.8 ± 5.0 years) that comprised 41 adnexae (unilateral, 9; bilateral, 16) were analyzed. Seventeen (68.0%), 5 (20.0%), and 3 (12.0%) procedures were performed by consultant gynecologists, subspecialty/specialist trainees, and consultant gynecologic oncologists, respectively. Twelve of 25 procedures (48.0%) were laparoscopic, and 13 of 25 procedures (52.0%) involved laparotomy. Four of 25 patients (16.0%; 95% confidence interval, 4.5-36.1%) or 4 of 41 adnexae (9.8%; 95% confidence interval, 2.7-23.1%) showed residual microscopic fimbrial tissue on the ovarian surface. Tubes/ovaries were free of adhesions in 23 cases. Two cases had dense adnexal adhesions, but neither had residual fimbrial tissue on the ovary. Residual fimbrial tissue was not associated significantly with surgical route or experience (consultant, 3/20 [15%]; trainee, 1/5 [20%]; P=1.0). CONCLUSION: Residual fimbrial tissue remains on the ovary after salpingectomy in a significant proportion of cases and could impact the level of risk-reduction that is obtained.

A bilingual advantage in 54-month-olds' use of referential cues in fast mapping.

Research has demonstrated a bilingual advantage in how young children use referential cues such as eye gaze and pointing gesture to locate an object or to categorize objects. This study investigated the use of referential cues (i.e. eye gaze) in fast mapping in three groups of children that differed in their language exposure. One hundred and seven 54-month-old children who were English monolinguals (n = 28), English-Mandarin bilinguals (n = 48), and English-Mandarin bilinguals with exposure to a third language (i.e. trilinguals, n = 31) were assessed with a word learning task using two types of test - a referent test and a mutual exclusivity test. During the task, following the gaze of an adult speaker was needed to be able to indicate the correct referent of a novel word at test. All three groups of children demonstrated successful word learning in explicit selection of and implicit looking time toward the target object during testing. However, bilingual and trilingual children outperformed their monolingual peers in both types of test when they were asked to explicitly select the correct objects. These findings suggest positive effects of bilingualism on children's use of referential cues in fast mapping.

Dearomative Intramolecular (4+3) Cycloadditions of Arenes with Epoxy and Aziridinyl Enolsilanes.

An intramolecular (4+3) cycloaddition of epoxy and aziridinyl enolsilanes with benzene, naphthalene, and anthracene derivatives is reported. Highly functionalized polycyclic alcohols and amines are generated under relatively mild reaction conditions with yields up to 89 %. Optically enriched cycloadducts are obtained from cycloadditions of enantiomerically pure epoxides and aziridines.

TMSBr-mediated solvent- and work-up-free synthesis of α-2-deoxyglycosides from glycals.

The thio-additions of glycals were efficiently promoted by a stoichiometric amount of trimethylsilyl bromide (TMSBr) to produce S-2-deoxyglycosides under solvent-free conditions in good to excellent yields. In addition, with triphenylphosphine oxide as an additive, the TMSBr-mediated direct glycosylations of glycals with a large range of alcohols were highly α-selective.

Direct synthesis of methyl phosphoramidates in carbohydrates.

A direct installation of a methyl phosphoramidate group by using methyl benzylphosphoramidochloridate into carbohydrates and amino acid is described. This one-step synthesis is efficient for both primary and secondary alcohols and exhibited excellent regioselectivity and functional group compatibility. Formation of a single diastereomer is observed in certain cases. The N-benzyl protecting group on methyl phosphoramidates is easily removed under mild conditions.

Concerted Ring Opening and Cycloaddition of Chiral Epoxy Enolsilanes with Dienes.

Silyl-triflate-catalyzed (4+3) cycloadditions of epoxy enolsilanes with dienes provide a mild and chemoselective synthetic route to seven-membered carbocycles. Epoxy enolsilanes containing a terminal enolsilane and a single stereocenter undergo cycloaddition with almost complete conservation of enantiomeric purity, a finding that argues against the involvement of oxyallyl cation intermediates which have been previously proposed for these types of reactions. Reported are theoretical and experimental investigations of the cycloaddition mechanism. The major enantiomers of the cycloadducts are derived from S(N)2-like reactions of the silylated epoxide with the diene, in which stereospecific ring opening and formation of the two new C-C bonds occur in a single step. Calculations predict, and experiments confirm, that the observed small losses of enantiomeric purity are traced to a triflate-mediated double S(N)2 cycloaddition pathway.

The impact of fibroid characteristics on pregnancy outcome.

OBJECTIVE: The objective of the study was to assess the influence of different characteristics of fibroids on pregnancy outcome. STUDY DESIGN: We identified women with fibroids 4 cm or greater in size on ultrasonography at the dating scan between January 2002 and December 2012. The size (4-7 cm, 7-10 cm, >10 cm), number (multiple/single), location (lower uterus/body of uterus), and type (intramural, combination of intramural/subserosal, subserosal) were ascertained. Medical records were reviewed to obtain pregnancy outcomes (preterm delivery, birthweight, mode of delivery, estimated blood loss, postpartum hemorrhage, and admission for fibroid-related pain). RESULTS: A total of 121 patients with 179 pregnancies were identified. Preterm delivery was more likely in those with multiple fibroids compared with single fibroids (18% vs 6%; P = .05). The location of the fibroid had an important effect on the mode of delivery with a higher cesarean section rate for fibroids in the lower part of uterus than in the body of the uterus (86% vs 40%; P = .01), a higher rate of postpartum hemorrhage (22% vs 11%; P = .03), and greater estimated blood loss (830 mL [SD, 551] vs 573 mL [SD, 383]; P = .03). Increasing size of fibroid was associated with greater rates of hemorrhage (11% vs 13% vs 36%; P = .04), increased estimated blood loss (567 mL [SD, 365] vs 643 mL [SD, 365] vs 961 mL [SD, 764]; P = .01), and higher rates of admissions for fibroid-related pain (5% vs 23% vs 21%; P = .01). CONCLUSION: Different fibroid characteristics affect pregnancy outcome in varying ways. This information can be used to aid counseling women antenatally and in risk-stratifying patients.

Evolution of fetal ventricular dilatation in relation to severity at first presentation.

BACKGROUND: To assess the outcome of 360 cases of fetal ventriculomegaly in a tertiary referral center. METHODS: Cases of fetal ventriculomegaly between June 1993 and December 2011 were identified from the departmental fetal database. The fetal medicine reports and obstetric notes were reviewed to ascertain the antenatal progression of the ventriculomegaly as well as the outcome of the pregnancy. Ventriculomegaly was defined by a lateral ventricular wall atrial measurement of greater than 10 mm. Cases were subdivided into mild (>10 to <12 mm), moderate (≥12 to <15 mm), and severe (≥15 mm). Termination of pregnancy was offered in cases where there were associated anomalies, aneuploidy, or the ventriculomegaly progressed. RESULTS: Of the 360 cases, 189 were mild, 79 were moderate, and 92 were severe. Sixty-four percent of cases had associated anomalies. Forty-six percent of cases in the mild group and 26% in the moderate group resolved. Only one case in the severe group improved. The mean rate of progression in the mild group was 1.07 (SD 1.03) mm/week, whereas in the moderate group progression was at a mean rate of 1.41 (SD 0.77) mm/week. Progression of severe ventriculomegaly was significantly higher at a mean rate of 3.26 (SD 2.92) mm/week (p = 0.007). CONCLUSIONS: The majority of fetuses with mild ventriculomegaly normalized, whereas the majority of moderate cases remained stable. The rate of progression of ventriculomegaly increased with severity. Fetuses with ventriculomegaly should be offered serial scans to allow the progression of ventriculomegaly to be ascertained with the option of late termination of pregnancy.

Stability and Analytical Characterization of Voriconazole as Measured by Immunoassay.

BACKGROUND: Voriconazole is a broad-spectrum triazole antifungal agent recommended for invasive fungal diseases, including invasive aspergillosis. Therapeutic drug monitoring via voriconazole target trough concentration is important to ensure efficacy while preventing toxicity. Our aim was to determine the stability of voriconazole as adapted and measured by an immunoassay. METHODS: Plasma from patient samples (n = 45) evaluated by a liquid chromatography with tandem mass spectrometry (LC-MS/MS) method was compared against an ARK immunoassay method, adapted and optimized on the Abbott Alinity c analyzer. Stability of voriconazole and analytical performance of ARK immunoassay was assessed, including functional sensitivity, limit of blank (LoB), limit of detection (LoD), and limit of quantification (LoQ), linearity, and precision. RESULTS: ARK voriconazole immunoassay was highly correlated (Pearson R = 0.988) to the LC-MS/MS method, with an average bias of 0.09 mg/L (2%). CV at LoQ of 0.5 mg/L was 3.7% while the functional sensitivity was established at 0.05 mg/L. Overall imprecision with liquid quality control material obtained from ARK was 5.0%, 6.3%, and 5.9% at 1 mg/L, 5 mg/L, and 10 mg/L, respectively. Limit of blank and LoD were 0.02 mg/L and 0.05 mg/L, respectively. Voriconazole in lithium heparin plasma separator tube declines over time, with a decrease that is more evident near or above toxic concentrations. CONCLUSION: Voriconazole collected in gel separation tubes declines over time, possibly due to absorptive properties. Voriconazole measurements by immunoassay and LC-MS/MS demonstrated acceptable comparability with sufficient level of sensitivity and precision.

Colour misbinding during motion rivalry.

When two dissimilar colours are displayed to the two eyes at overlapping retinal locations, binocular rivalry typically results: a fluctuating struggle for perceptual dominance of each eye's stimulus. We found instead that isoluminant counter-rotating patterns consisting of coloured and achromatic portions can promote an illusory colour 'misbinding', where the colours from both eyes were perceived within a single rotating pattern. The achromatic portion of one rotating pattern thus appeared to take on the colour of the other, oppositely rotating pattern. The results suggest that the neural mechanisms of colour binding can operate even while representations of the same patterns' motions are undergoing rivalry, and support the idea that rivalry can occur in isolation within the motion system.

Machine Learning Techniques, Applications, and Potential Future Opportunities in Pressure Injuries (Bedsores) Management: A Systematic Review.

Pressure Injuries (PI) are one of the most common health conditions in the United States. Most acute or long-term care patients are at risk of developing PI. Machine Learning (ML) has been utilized to manage patients with PI, in which one systematic review describes how ML is used in PI management in 32 studies. This research, different from the previous systematic review, summarizes the previous contributions of ML in PI from January 2007 to July 2022, categorizes the studies according to medical specialties, analyzes gaps, and identifies opportunities for future research directions. PRISMA guidelines were adopted using the four most common databases (PubMed, Web of Science, Scopus, and Science Direct) and other resources, which result in 90 eligible studies. The reviewed articles are divided into three categories based on PI time of occurrence: before occurrence (48%); at time of occurrence (16%); and after occurrence (36%). Each category is further broken down into sub-fields based on medical specialties, which result in sixteen specialties. Each specialty is analyzed in terms of methods, inputs, and outputs. The most relevant and potentially useful applications and methods in PI management are outlined and discussed. This includes deep learning techniques and hybrid models, integration of existing risk assessment tools with ML that leads to a partnership between provider assessment and patients' Electronic Health Records (EHR).

An Integrated System of Multifaceted Machine Learning Models to Predict If and When Hospital-Acquired Pressure Injuries (Bedsores) Occur.

Hospital-Acquired Pressure Injury (HAPI), known as bedsore or decubitus ulcer, is one of the most common health conditions in the United States. Machine learning has been used to predict HAPI. This is insufficient information for the clinical team because knowing who would develop HAPI in the future does not help differentiate the severity of those predicted cases. This research develops an integrated system of multifaceted machine learning models to predict if and when HAPI occurs. Phase 1 integrates Genetic Algorithm with Cost-Sensitive Support Vector Machine (GA-CS-SVM) to handle the high imbalance HAPI dataset to predict if patients will develop HAPI. Phase 2 adopts Grid Search with SVM (GS-SVM) to predict when HAPI will occur for at-risk patients. This helps to prioritize who is at the highest risk and when that risk will be highest. The performance of the developed models is compared with state-of-the-art models in the literature. GA-CS-SVM achieved the best Area Under the Curve (AUC) (75.79 ± 0.58) and G-mean (75.73 ± 0.59), while GS-SVM achieved the best AUC (75.06) and G-mean (75.06). The research outcomes will help prioritize at-risk patients, allocate targeted resources and aid with better medical staff planning to provide intervention to those patients.

An Integrated System of Braden Scale and Random Forest Using Real-Time Diagnoses to Predict When Hospital-Acquired Pressure Injuries (Bedsores) Occur.

BACKGROUND AND OBJECTIVES: Bedsores/Pressure Injuries (PIs) are the second most common diagnosis in healthcare system billing records in the United States and account for 60,000 deaths annually. Hospital-Acquired Pressure Injuries (HAPIs) are one classification of PIs and indicate injuries that occurred while the patient was cared for within the hospital. Until now, all studies have predicted who will develop HAPI using classic machine algorithms, which provides incomplete information for the clinical team. Knowing who will develop HAPI does not help differentiate at which point those predicted patients will develop HAPIs; no studies have investigated when HAPI develops for predicted at-risk patients. This research aims to develop a hybrid system of Random Forest (RF) and Braden Scale to predict HAPI time by considering the changes in patients' diagnoses from admission until HAPI occurrence. METHODS: Real-time diagnoses and risk factors were collected daily for 485 patients from admission until HAPI occurrence, which resulted in 4619 records. Then for each record, HAPI time was calculated from the day of diagnosis until HAPI occurrence. Recursive Feature Elimination (RFE) selected the best factors among the 60 factors. The dataset was separated into 80% training (10-fold cross-validation) and 20% testing. Grid Search (GS) with RF (GS-RF) was adopted to predict HAPI time using collected risk factors, including Braden Scale. Then, the proposed model was compared with the seven most common algorithms used to predict HAPI; each was replicated for 50 different experiments. RESULTS: GS-RF achieved the best Area Under the Curve (AUC) (91.20 ± 0.26) and Geometric Mean (G-mean) (91.17 ± 0.26) compared to the seven algorithms. RFE selected 43 factors. The most dominant interactable risk factors in predicting HAPI time were visiting ICU during hospitalization, Braden subscales, BMI, Stimuli Anesthesia, patient refusal to change position, and another lab diagnosis. CONCLUSION: Identifying when the patient is likely to develop HAPI can target early intervention when it is needed most and reduces unnecessary burden on patients and care teams when patients are at lower risk, which further individualizes the plan of care.

The RNA binding protein Larp1 regulates cell division, apoptosis and cell migration.

The RNA binding protein Larp1 was originally shown to be involved in spermatogenesis, embryogenesis and cell-cycle progression in Drosophila. Our data show that mammalian Larp1 is found in a complex with poly A binding protein and eukaryote initiation factor 4E and is associated with 60S and 80S ribosomal subunits. A reduction in Larp1 expression by siRNA inhibits global protein synthesis rates and results in mitotic arrest and delayed cell migration. Consistent with these data we show that Larp1 protein is present at the leading edge of migrating cells and interacts directly with cytoskeletal components. Taken together, these data suggest a role for Larp1 in facilitating the synthesis of proteins required for cellular remodelling and migration.