Hypocomplementaemic and normocomplementaemic multiple sclerosis. Genetic determinism and association with specific HLA determinants (B18 and B7).
Seventy-five patients with multiple sclerosis (MS) were treated for complement components C3, after factor B, C4, and tested for HLA-A and B-determinants. Levels of IgG, IgA, IgD, IgE and titres of measles antibodies were also determined. Correlations between these immunological values and HLA determinants could be obtained in siblings, parents and/or children of the patients in 13 families. B18 frequency is strongly associated with the hypocomplementaemic group (x2 = 8.9). An association of B18 with the population of cases with low B levels is also found (x2 = 8.02). Familial data showed that low C3 and/or low B levels are associated with the HLA haplotyes, especially with those containing B18. A "complement abnormality susceptibility gene", linked to the HLA genes, is postulated. Infections are significantly more frequent in families of hypocomplementaemic MS, the existence of a genetic immunodeficiency affecting the synthesis of the complement components, linked to the HLA determinants. In 1 case studied in this article, a heterozygous C2 deficiency linked to HLA-A10, B18 was found and might confirm this hypothesis.


Effects of disease activity on lipoprotein levels in patients with early arthritis: can oxidized LDL cholesterol explain the lipid paradox theory?
An increased risk of cardiovascular (CV) complications has been described in patients with rheumatoid arthritis (RA). It is the result of the combined effect of classic CV risk factors and others that are specific to the disease. We assessed data from 448 early arthritis (EA) patients: 79% women, age (median [p25-p75]) at onset: 55 [44-67] years and disease duration at study entry 5 [3-8] months; and 72% fulfilled the 1987 RA criteria at 2 years of follow-up. Rheumatoid factor was positive in 54% of patients and anti-citrullinated peptide antibodies in 50%. The follow-up of patients ranged from 2 to 5 years with more than 1400 visits with lipoprotein measurements available (mean 2.5 visits/patient). Demographic- and disease-related variables were systematically recorded. Total cholesterol (TC), high-density lipoprotein (HDL-C), and low-density lipoprotein (LDL-C) levels were obtained from routine laboratory tests. Oxidized-LDL (oxLDL-C) levels were assessed using a commercial ELISA kit. We fitted population-averaged models nested by patient and visit to determine the effect of independent variables on serum levels of TC, its fractions, and oxLDL-C. After adjustment for several confounders, high-disease activity was significantly associated with decreased TC, HDL-C, and LDL-C levels and increased oxLDL-C levels. Standardized coefficients showed that the effect of disease activity was greater on oxLDL-C and HDL-C. Interestingly, we observed that those patients with lower levels of LDL-C showed higher oxLDL-C/LDL-C ratios. High-disease activity in EA patients results in changes in the HDL-C and oxLDL-C levels, which in turn may contribute to the increased risk of CV disease observed in these patients.


Dietary Intake of Hydrolyzable Tannins and Condensed Tannins to Regulate Lipid Metabolism.
Lipid metabolism disorder is a multifactor issue, which contributes to several serious health consequences, such as obesity, hyperlipidemia, atherosclerosis diabetes, non-alcoholic fatty liver, etc. Tannins, applied as naturally derived plants, are commonly used in the study of lipid metabolism disease with excellent safety and effectiveness while producing less toxic and side effects. Meanwhile, recognition of the significance of dietary tannins in lipid metabolism disease prevention has increased. As suggested by existing evidence, dietary tannins can reduce lipid accumulation, block adipocyte differentiation, enhance antioxidant capacity, increase the content of short-chain fatty acids, and lower blood lipid levels, thus alleviating lipid metabolism disorder. This study is purposed to sum up and analyze plenty of documents on tannins, so as to provide the information required to assess the lipid metabolism of tannins.


Cardiac prognosis in hypertensive patients. Incidence of sudden death and ventricular arrhythmias.
The cardiac prognosis of hypertensive patients has been able to be precisely determined over the last 20 years as a result of large-scale epidemiologic surveys. The incidence of ischemic heart disease and the importance of left ventricular hypertrophy have been clearly defined in the literature. In contrast, the incidence of sudden death and ventricular arrhythmias has been poorly taken into account, although hypertension increases the risk of sudden death to the same degree as coronary artery disease. The relative risk increases progressively as a function of the quintiles of distribution of blood pressure, reaching a value of 3.2 for the highest quintile. There is also a significant correlation between hypertension and ventricular arrhythmias. Hypertensive subjects with other cardiovascular risk factors such as hypercholesterolemia or smoking and with ventricular extrasystoles, reflecting the presence of silent ischemia, can be considered to be at high risk of cardiac death.


Using Stereoscopic Virtual Presentation for Clinical Anatomy Instruction and Procedural Training in Medical Education.
This chapter begins by exploring the current landscape of virtual and augmented reality technologies in a post-pandemic world and asserting the importance of virtual technologies that improve students' learning outcomes while also reducing costs. Next, the chapter describes clinical anatomy instruction concepts in medical education, including applied anatomy content knowledge, pedagogical anatomy content knowledge, and virtual stereoscopic visualization studies that exemplify these concept areas, respectively. The chapter then explores the concept of procedural training with a specific emphasis on virtual stereoscopic anatomy visualization studies that exemplify or have implications for procedural training in medical education. Subsequently, the chapter discusses the benefits and challenges as well as the potential future positive and negative implications of virtual stereoscopic visualizations in medical education before finally concluding with some pensive considerations for the present and future of anatomy education and training using virtual technologies.


Cell-surface protein-protein interaction analysis with time-resolved FRET and snap-tag technologies.
Förster resonance energy transfer (FRET) is a proximity-dependent quantum effect that allows the measurement of protein interactions and conformational changes which are invisible to traditional forms of fluorescence or electron microscopy. However, FRET experiments often have difficulty detecting interactions that are transient and localized or occur in low abundance against a large background. This protocol describes a method of improving on the sensitivity and quantifiability of FRET experiments by using time-specific detection to isolate FRET-mediated acceptor emission from cross-talk excitation and all other sources of nonspecific fluorescence background.


Suction Use During Endourological Procedures.
Equipment used in endourology is constantly evolving due to increasing incidence of urolithiasis. Suctioning has been used mainly in PCNL in conjunction with ultrasonic and ballistic devices for stone removal. Recently technological advances permitted the use of suctioning in more endourological techniques. This review aims to summarize the literature regarding these advancements and analyze the upcoming results. Several centers have conducted experimental and clinical studies on suctioning use during PCNL, mPCNL, and ureteroscopy and concluded that it is an effective and safe adjustment that improves stone-free rates and limits complication rates after these procedures. Suctioning use during common endourological procedures led to improved safety and efficacy among several indications. Due to the observational nature and small sample size of many studies, larger RCTs are needed to make safe conclusions.


Can we still do something-and what?-for a seemingly missing syndrome?
Although several modifiable risk factors have been identified, and prone and side sleep positions were identified as preventing sudden infant death syndrome (SIDS), the epidemiology of sudden unexpected deaths in infancy (SUDI), which includes SIDS, has not unchanged in over a decade. What can be done? Italian infant mortality rates were analysed between 1996 and 2015. Between 1996 and 2015 in Italy 1152 SUDI deaths were reported in infants less than one year old. SUDI decreased substantially from 18 in 1996 to 10.2 deaths per hundred live births in 2015 (- 43%), the contribution was the change in the SIDS rate from 11.3 to 4.1 (- 64%). However, since 1004 main and SIDS rates have not changed. Interventions that support safe sleep must be maintained, but research is still needed since although these dramatic deaths have been reduced their causes remain unknown. The challenge is now to shift their trend which has been constant for too long.


A hybrid-assembly approach towards nitrogen-doped graphene aerogel supported cobalt nanoparticles as high performance oxygen reduction electrocatalysts.
As a novel electrocatalyst for oxygen reduction reaction (ORR), nitrogen-doped graphene aerogel supported cobalt nanoparticles (Co-NGA) is archived by a hybrid-assembly of graphene oxide (GO), o-phthalonitrile and cobalt acetate and the following thermal treatment. The hybrid-assembly process successfully combines the ionic assembly of GO sheets and Co ions with the coordination between o-phthalonitrile and Co ions, which can be converted to nitrogen doped carbon and Co nanoparticles in the pyrolysis process under nitrogen flow. Remarkable features of Co-NGA including the macroporous graphene scaffolds, high surface area, and N/Co-doping effect can lead to a high catalytic efficiency for ORR. As the results, the composites pyrolyzed at 600°C (Co-NGA600) shows excellent electrocatalytic activities and kinetics for ORR in basic media, which are comparable with those of Pt/C catalyst, together with superior durability.


Visual attention amplifies response priming of pointing movements to color targets.
We studied the influence of spatial visual attention on the time course of primed pointing movements. We measured pointing responses to color targets preceded by color stimuli priming either the same response as the target or the opposite response. The effects of visual attention at the prime and target locations were studied by varying both the cue-prime and prime-target intervals when presenting either exogenous attentional cues or, in a separate experiment, endogenous cues whose processing was a precondition for performing the task. Pointing trajectories revealed large priming effects in which pointing responses were first controlled by prime signals and then captured in midflight by target signals. Priming effects were strongly amplified when the relevant prime locations were visually attended at optimal cue-prime SOAs, with attention modulating the entire time course of the primed pointing movements. We propose that visual attention amplifies the earliest waves of visuomotor feedforward information, elicited in turn by primes and by targets.


Production of androgenetic diploid loach by cold-shock of eggs fertilized with diploid sperm.
Diploid androgenotes were produced without egg irradiation in the loach, Misgurnus anguillicaudatus. Eggs of wild-type diploid females were fertilized with diploid sperm of a neo-tetraploid male and then cold-shock treated at 3 °C (range, ±0.5 °C) for 30 minutes just after fertilization to eliminate the female nucleus. After hatching, ploidy status of the hatched larvae was analyzed by flow cytometry, which revealed putative diploid androgenotes as well as larvae possessing other ploidies. Five independent microsatellite DNA markers were genotyped to confirm all-male inheritance of the resultant diploid larvae. The mean ± SD yield rate of diploid androgenetic larvae to total eggs used was 12.29 ± 3.25% in the cold-shock group and 22.23 ± 13.42% in the UV-irradiated group (P > 0.05). No diploid androgenetic larvae were detected in the intact control group. To our knowledge, this is the first report demonstrating successful induction of diploid androgenotes without egg irradiation in fish.


Transcriptional regulation in the innate immune system.
In cells of the innate immune system, the transcriptional response to a microbial stimulus is tailored to both the stimulus and cell type, suggesting the existence of highly sophisticated regulatory mechanisms. Early studies suggested that specificity is dictated by sets of differentially induced transcription factors that synergistically activate target genes containing their binding sites. However, recent studies have revealed additional interrelated regulatory layers, which are the topic of this article. In particular, individual transcription factors may require different post-translational modifications and coregulatory interactions to regulate different target genes. Furthermore, competence for induction is programmed at an early stage of development by factors involved in lineage commitment, and the architecture and chromatin structure of each promoter play critical roles in transcriptional specificity.


Management of Colorectal Cancer in Older Adults.
Treatment for colorectal cancer should not be based on age alone. Pooled analyses from clinical trials show that fit older adults are able to tolerate treatment well with similar efficacy as younger adults. When an older adult is considered for treatment, the clinical encounter must evaluate for deficits in physical and cognitive function, and assess comorbidities, medications, and the degree of social support, all which have may affect tolerance of treatment. Based on the degree of fitness of the patient, multiple alternatives to aggressive treatment regimens and strategies exist to minimize toxicity and preserve quality of life during treatment.


alpha 2-Macroglobulin binding to cultured fibroblasts. Solubilization and partial purification of binding sites.
Binding sites having the characteristics of receptors for "activated" alpha 2-macroglobulin (alpha 2M) have been solubilized with octyl-beta-D-glucoside from fibroblast membranes. When the detergent was removed by dialysis, the resulting insoluble extract was shown to bind 125I-alpha 2M specifically. Analysis of the binding data using a nonlinear curve-fitting program suggests that the solubilized preparation contains two classes of binding sites (KD = 0.34 nM and KD = 104 nM). Membranes or solubilized extracts from KB cells which lack alpha 2M binding sites did not specifically bind 125I-alpha 2M. The solubilized binding sites from fibroblasts were inactivated by boiling and trypsin treatment, and required Ca+2 for maximal binding. In addition, the high affinity binding of 125I-alpha 2M to the solubilized receptor was inhibited by bacitracin and by alpha-bromo-5-iodo-4-hydroxy-3-nitroacetophenone, two agents which interfere with the uptake of alpha 2M in cultured fibroblasts. Using a combination of ion exchange and gel permeation chromatography, we have purified the high affinity alpha 2M binding site approximately 100-fold from membrane derived from NIH-3T3 (spontaneously transformed) fibroblasts grown as tumors in mice. The receptor is apparently an acidic protein and the receptor octyl-beta-D-glucoside complex has a Stokes radius of 45-50 A as measured by gel filtration.


The human microglial HMC3 cell line: where do we stand? A systematic literature review.
Microglia, unique myeloid cells residing in the brain parenchyma, represent the first line of immune defense within the central nervous system. In addition to their immune functions, microglial cells play an important role in other cerebral processes, including the regulation of synaptic architecture and neurogenesis. Chronic microglial activation is regarded as detrimental, and it is considered a pathogenic mechanism common to several neurological disorders. Microglial activation and function have been extensively studied in rodent experimental models, whereas the characterization of human cells has been limited due to the restricted availability of primary sources of human microglia. To overcome this problem, human immortalized microglial cell lines have been developed. The human microglial clone 3 cell line, HMC3, was established in 1995, through SV40-dependent immortalization of human embryonic microglial cells. It has been recently authenticated by the American Type Culture Collection (ATCC®) and distributed under the name of HMC3 (ATCC®CRL-3304). The HMC3 cells have been used in six research studies, two of which also indicated by ATCC® as reference articles. However, a more accurate literature revision suggests that clone 3 was initially distributed under the name of CHME3. In this regard, several studies have been published, thus contributing to a more extensive characterization of this cell line. Remarkably, the same cell line has been used in different laboratories with other denominations, i.e., CHME-5 cells and C13-NJ cells. In view of the fact that "being now authenticated by ATCC®" may imply a wider distribution of the cells, we aimed at reviewing data obtained with the human microglia cell line clone 3, making the readers aware of this complicated nomenclature. In addition, we also included original data, generated in our laboratory with the HMC3 (ATCC®CRL-3304) cells, providing information on the current state of the culture together with supplementary details on the culturing procedures to obtain and maintain viable cells.


Anterior open bite correction by Le Fort I osteotomy with or without anterior segmentation: which is more stable?
A retrospective cohort study was conducted to analyze the relapse rate of anterior open bite (AOB) correction comparing Le Fort I osteotomy with and without anterior segmentation. The risk factors that might contribute to relapse were also assessed. Lateral cephalograms obtained at six different times were analyzed. A total of 81 patients with AOB were recruited. Thirty-five patients underwent Le Fort I osteotomy without anterior segmentation and 46 patients underwent anterior segmentation. Le Fort I osteotomy with anterior segmentation resulted in significantly more AOB relapse when compared to that without anterior segmentation at 7 weeks postoperative (15.2% vs. 0%, P=0.016). During the early postoperative period, factors that contributed to AOB relapse in Le Fort I osteotomy with anterior segmentation were AOB closure ≥4mm and inferior positioning of the anterior segment >2mm. Over the long term, AOB closure ≥4mm and intraoral vertical ramus osteotomy as the only mandibular procedure were factors identified as causing more AOB relapse in those treated by Le Fort I osteotomy with anterior segmentation. In conclusion, Le Fort I osteotomy without anterior segmentation was found to be more stable in the surgical correction of AOB in the early and late postoperative periods.


Separation of human glycoprotein hormones and their subunits by reversed-phase liquid chromatography.
Separation of human pituitary follicle-stimulating hormone (FSH), luteinizing hormone (LH) and thyroid-stimulating hormone (TSH) was effected on a micro-scale by reversed-phase high-performance liquid chromatography (HPLC) on a SynChropak C1 column in series with a Vydac C4 column using a linear gradient of acetonitrile in 0.1 M triethylamine phosphate buffer at pH 6.5. Chromatography on the C4 column alone caused partial dissociation of FSH into its subunits, whereas LH and TSH remained intact. Good yields of the separated subunits were obtained after prior dissociation of each hormone, and the results show that reversed-phase HPLC is useful for the analytical and preparative separation of these structurally related hormones and their subunits.


Mitochondrial disease genetics update: recent insights into the molecular diagnosis and expanding phenotype of primary mitochondrial disease.
Primary mitochondrial disease (PMD) is a genetically and phenotypically diverse group of inherited energy deficiency disorders caused by impaired mitochondrial oxidative phosphorylation (OXPHOS) capacity. Mutations in more than 350 genes in both mitochondrial and nuclear genomes are now recognized to cause primary mitochondrial disease following every inheritance pattern. Next-generation sequencing technologies have dramatically accelerated mitochondrial disease gene discovery and diagnostic yield. Here, we provide an up-to-date review of recently identified, novel mitochondrial disease genes and/or pathogenic variants that directly impair mitochondrial structure, dynamics, and/or function. A review of PubMed publications was performed from the past 12 months that identified 16 new PMD genes and/or pathogenic variants, and recognition of expanded phenotypes for a wide variety of mitochondrial disease genes. Broad-based exome sequencing has become the standard first-line diagnostic approach for PMD. This has facilitated more rapid and accurate disease identification, and greatly expanded understanding of the wide spectrum of potential clinical phenotypes. A comprehensive dual-genome sequencing approach to PMD diagnosis continues to improve diagnostic yield, advance understanding of mitochondrial physiology, and provide strong potential to develop precision therapeutics targeted to diverse aspects of mitochondrial disease pathophysiology.


Specific methods for the determination of radioactivity in D-(-)-3-hydroxybutyrate in blood plasma.
Two simple, high-yield rapid methods with good reproducibility are described, which permit the determination of radioactivity in plasma D-(-)-3-hydroxybutyrate. The compound is converted to acetoacetate, using a modified enzymatic method. In procedure 1, acetoacetate is reacted with 2,4-dinitrophenylhydrazine; the resulting hydrazone is oxidised by means of a sample oxidiser, and the product 14CO2 is collected in scintillation liquid and counted. In procedure 2, a Conway microdiffusion unit is applied. The acetoacetate is decarboxylated to acetone in the presence of o-phenylenediamine, and the acetone is then diffused into semicarbazide solution. This solution, containing the semicarbazone derivative of labelled acetone, is transferred to liquid scintillation and counted. In both procedures the radioactivity is measured simultaneously in a separate sample which was not subjected to the enzymatic conversion of D-(-)-3-hydroxybutyrate. The difference in radioactivity between the two samples is attributed to labelled (D-(-)-3-hydroxybutyrate.


Age-related differences in the occurrence, severity, and distress of symptoms in older patients at the initiation of chemotherapy.
Evaluate for differences in occurrence, severity, and distress ratings for 32 symptoms between younger older adults (YOA, < 70 years) and older adults (OA, ≥ 70 years) at initiation of chemotherapy. Patients (n = 125) were recruited prior to the initiation of chemotherapy and completed the Memorial Symptom Assessment Scale. Differences in occurrence, severity, and distress ratings were evaluated using Independent sample t-tests and Chi-square or Fisher's exact tests. On average, the older patients reported ten concurrent symptoms that equates with a moderate symptom burden. Symptoms with the highest occurrence rates were not always the most severe and/or the most distressing. Few age-related differences were found in patients' symptom experiences. When age-related differences were identified, OA reported lower occurrence, severity, and distress ratings. Nine of the ten symptoms with highest occurrence rates were common for both age groups. For severity and distress, only half of the symptoms were common. In terms of severity and distress, all of the top ten ranked symptoms were in the moderate to severe range. Both YOA and OA reported a moderate symptom burden and severity and distress scores in the moderate to severe range. The symptoms with the highest occurrence rates were not always the most severe/or the most distressing. Our findings suggest that different dimensions of the symptom experience (i.e., occurrence, severity, and distress) warrant evaluation in older oncology patients.


A primary cellular fibrohistiocytoma of the lung: Report of a case.
Cellular fibrohistiocytoma (CFH) is a type of fibrohistiocytic tumor that commonly occurs in the dermis and superficial subcutis. The designation is used for lesions that show increased cellularity with a fascicular growth pattern and frequent extension. Our search of literature only revealed one case of a primary CFH of the lung. We experienced a rare patient with a primary CFH of the lung. We herein present a rare case of a 77-year-old female patient without a cutaneous lesion, who underwent resection for what was considered to be a primary CFH of the lung. There has been no recurrence including a cutaneous lesion in a year after surgery. CFH is considered to be benign, but rare cases showing multiple recurrences and involving metastasis to the lymph nodes and internal organs have been reported. At present, it is not possible to predict this aggressive biological behavior based on the tumor histology. It is essential to perform resection with an adequate margin with close clinical follow-up.


Impact of millimeter-level margins on peripheral normal brain sparing for gamma knife radiosurgery.
To investigate how millimeter-level margins beyond the gross tumor volume (GTV) impact peripheral normal brain tissue sparing for Gamma Knife radiosurgery. A mathematical formula was derived to predict the peripheral isodose volume, such as the 12-Gy isodose volume, with increasing margins by millimeters. The empirical parameters of the formula were derived from a cohort of brain tumor and surgical tumor resection cavity cases (n=15) treated with the Gamma Knife Perfexion. This was done by first adding margins from 0.5 to 3.0 mm to each individual target and then creating for each expanded target a series of treatment plans of nearly identical quality as the original plan. Finally, the formula was integrated with a published logistic regression model to estimate the treatment-induced complication rate for stereotactic radiosurgery when millimeter-level margins are added. Confirmatory correlation between the nominal target radius (ie, RT) and commonly used maximum target size was found for the studied cases, except for a few outliers. The peripheral isodose volume such as the 12-Gy volume was found to increase exponentially with increasing Δ/RT, where Δ is the margin size. Such a curve fitted the data (logarithmic regression, R(2) >0.99), and the 12-Gy isodose volume was shown to increase steeply with a 0.5- to 3.0-mm margin applied to a target. For example, a 2-mm margin on average resulted in an increase of 55% ± 16% in the 12-Gy volume; this corresponded to an increase in the symptomatic necrosis rate of 6% to 25%, depending on the Δ/RT values for the target. Millimeter-level margins beyond the GTV significantly impact peripheral normal brain sparing and should be applied with caution. Our model provides a rapid estimate of such an effect, particularly for large and/or irregularly shaped targets.


Exploring the Clinical Utility of Gustatory Dysfunction (GD) as a Triage Symptom Prior to Reverse Transcription Polymerase Chain Reaction (RT-PCR) in the Diagnosis of COVID-19: A Meta-Analysis and Systematic Review.
The diagnosis of COVID-19 is made using reverse transcription polymerase chain reaction (RT-PCR) but its sensitivity varies from 20 to 100%. The presence of gustatory dysfunction (GD) in a patient with upper respiratory tract symptoms might increase the clinical suspicion of COVID-19. To perform a systematic review and meta-analysis to determine the pooled sensitivity, specificity, positive likelihood ratio (LR+), negative likelihood ratio (LR-) and diagnostic odds ratio (DOR) of using GD as a triage symptom prior to RT-PCR. PubMed and Embase were searched up to 20 June 2021. Studies published in English were included if they compared the frequency of GD in COVID-19 adult patients (proven by RT-PCR) to COVID-19 negative controls in case control or cross-sectional studies. The Newcastle-Ottawa scale was used to assess the methodological quality of the included studies. 21,272 COVID-19 patients and 52,298 COVID-19 negative patients were included across 44 studies from 21 countries. All studies were of moderate to high risk of bias. Patients with GD were more likely to test positive for COVID-19: DOR 6.39 (4.86-8.40), LR+ 3.84 (3.04-4.84), LR- 0.67 (0.64-0.70), pooled sensitivity 0.37 (0.29-0.47) and pooled specificity 0.92 (0.89-0.94). While history/questionnaire-based assessments were predictive of RT-PCR positivity (DOR 6.62 (4.95-8.85)), gustatory testing was not (DOR 3.53 (0.98-12.7)). There was significant heterogeneity among the 44 studies (I2 = 92%, p < 0.01). GD is useful as a symptom to determine if a patient should undergo further testing, especially in resource-poor regions where COVID-19 testing is scarce. Patients with GD may be advised to quarantine while repeated testing is performed if the initial RT-PCR is negative. None.


Diabetes mellitus and cardiothoracic surgical site infections.
Persons afflicted with diabetes mellitus compose over one fourth of patients undergoing cardiothoracic surgery and create a particular challenge to surgical and critical care practitioners. This paper reviews the impact of diabetes mellitus on cardiothoracic surgical site infection (SSI) risk, with specific attention to recent data regarding the role of perioperative hyperglycemia as well as the use of continuous insulin infusion for SSI risk reduction in the cardiothoracic surgical population.


Solid-phase microextraction fibre-water distribution constants of more hydrophobic organic compounds and their correlations with octanol-water partition coefficients.
Fibre coating-water distribution constants (Kfw) of more hydrophobic chemicals were determined with six different solid-phase microextraction fibre types (including a polyoctylmethylsiloxane (C8) prototype) by fibre exposure to agitated large-volume water samples lasting several days. The results obtained are comparable with Kfw values obtained under dynamic conditions. Octanol-water partition coefficients (Kow) were measured with the mixture of distributing substances to examine log Kfw-log Kow relationships based on a consistent dataset. Kfw values obtained with liquid polymer fibre coatings correlate reasonably well with the hydrophobicity of the test compounds (with decreasing sensitivity in the following order: 7 microm polydimethylsiloxane (PDMS)>100 microm PDMS>C8>polyacrylate) whereas this is not the case with the PDMS-divinylbenzene (DVB) and Carbowax-DVB fibres, partially porous coatings which provide the highest Kfw values for all substances tested.


Intermittent lab earthquakes in dynamically weakening fault gouge.
Large and destructive earthquakes on mature faults in Earth's crust occur as slip in a layer of a fine granular material-fault gouge-produced by comminution during sliding1,2. A range of insights into the frictional resistance of faults-one of the main factors controlling earthquake nucleation, dynamic propagation and arrest, and hence the destructive ground shaking of earthquakes2,3-has been obtained in experiments with spatially uniform slip imposed in small samples2,4-21. However, how various features of gouge friction combine to determine spontaneous progression of earthquakes is difficult to study in the lab owing to substantial challenges with sample sizes and adequate imaging22. Here, using lab experiments, we show that spontaneously propagating dynamic ruptures navigate a fault region with fine rock gouge through complex, intermittent slip processes with dramatic friction evolution. These include repeated arrest of rupture propagation caused by friction strengthening at lower slip rates and dynamic earthquake re-nucleation enabled by pronounced rapid friction weakening at higher slip rates consistent with flash heating8,12,23. The spontaneous repeated weakening and strengthening of friction in fine rock gouge highlights the fundamental dependence of friction on slip rate and associated processes, such as shear heating, localization and delocalization of shear, and dilation and compaction of the shear layer6,7,9-21. Our findings expand experimental support9,11 of the concept that co-seismic weakening may enable earthquake rupture to break through stable fault regions24,25, with substantial implications for seismic hazard.


Methodological Approaches for Assessing Metabolomic Changes in Glioblastomas.
Glioblastoma (GBM), a highly malignant primary brain tumor, inevitably leads to death. In the last decade, a variety of novel molecular characteristics of GBMs were unraveled. The identification of the mutation in the IDH1 and less commonly IDH2 gene was surprising and ever since has nurtured research in the field of GBM metabolism. While initially thought that mutated IDH1 were to act as a loss of function mutation it became clear that it conferred the production of an oncometabolite that in turn substantially reprograms GBM metabolism. While mutated IDH1 represents truly the tip of the iceberg, there are numerous other related observations in GBM that are of significant interest to the field, including the notion that oxidative metabolism appears to play a more critical role than believed earlier. Metabolic zoning is another important hallmark of GBM since it was found that the infiltrative margin that drives GBM progression reveals enrichment of fatty acid derivatives. Consistently, fatty acid metabolism appears to be a novel therapeutic target for GBM. How metabolism in GBM intersects is another pivotal issue that appears to be important for its progression and response and resistance to therapies. In this review, we will summarize some of the most relevant findings related to GBM metabolism and cell death and how these observations are influencing the field. We will provide current approaches that are applied in the field to measure metabolomic changes in GBM models, including the detection of unlabeled and labeled metabolites as well as extracellular flux analysis.


Self-proteolysis regulation in the Bothrops jararaca venom: the metallopeptidases and their intrinsic peptidic inhibitor.
Snake venom proteome variation is a well-documented phenomenon, whereas peptidome variation is still relatively unknown. We used a biological approach to explore the inhibitory activities present in the whole venom of Bothrops jararaca that prevents the venom self-proteolysis and/or digestion of the glandular tissue. Although snake venom metallopeptidases have long been known from the biochemical up to the clinical point of view, the mechanisms by which these enzymes are regulated in the reptile's venom gland remain fairly unknown. We have successfully demonstrated that there are three synergistic weak inhibitory mechanisms that are present in the crude venom that are able to abolish the metallopeptidase activity in situ, namely: (i) citrate calcium chelation; (ii) acidic pH and; (iii) enzymatic competitive inhibition by the tripeptide Pyroglutamyl-lysyl-tryptophan. Taken together, these three factors become a strong set-up that inhibits the crude venom metallopeptidase activity as well as a purified metallopeptidase from this same venom. However, this inhibition can be totally reverted by dilution into an optimal pH solution, such as the blood.


Interest of exome sequencing trio-like strategy based on pooled parental DNA for diagnosis and translational research in rare diseases.
Exome sequencing (ES) has become the most powerful and cost-effective molecular tool for deciphering rare diseases with a diagnostic yield approaching 30%-40% in solo-ES and 50% in trio-ES. We applied an innovative parental DNA pooling method to reduce the parental sequencing cost while maintaining the diagnostic yield of trio-ES. We pooled six (Agilent-CRE-v2-100X) or five parental DNA (TWIST-HCE-70X) aiming to detect allelic balance around 8-10% for heterozygous status. The strategies were applied as second-tier (74 individuals after negative solo-ES) and first-tier approaches (324 individuals without previous ES). The allelic balance of parental-pool variants was around 8.97%. Sanger sequencing uncovered false positives in 1.5% of sporadic variants. In the second-tier approach, we evaluated than two thirds of the Sanger validations performed after solo-ES (41/59-69%) would have been saved if the parental-pool segregations had been available from the start. The parental-pool strategy identified a causative diagnosis in 18/74 individuals (24%) in the second-tier and in 116/324 individuals (36%) in the first-tier approaches, including 19 genes newly associated with human disorders. Parental-pooling is an efficient alternative to trio-ES. It provides rapid segregation and extension to translational research while reducing the cost of parental and Sanger sequencing.


Comprehensive evaluation on water resource carrying capacity in karst areas using cloud model with combination weighting method: a case study of Guiyang, southwest China.
It is important to maintain the sustainable development of water resources. Objective assessment on water resource carrying capacity (WRCC) is beneficial to the formulation of scientific and reasonable water management practices. In view of the problem that evaluation indicators of WRCC cannot describe the fuzziness and randomness, a cloud model was introduced into regional WRCC assessment. This study selected a typical karst area (Guiyang) as the research object to study WRCC by using cloud model with combination weighting method. WRCC was assessed from the following five dimensions: water environment subsystem, social subsystem, economic subsystem, ecological subsystem, and humanities (water resource management and policy regulation) subsystem. In addition, evaluation results after normalizing all of indicators data were also calculated. And these two kinds of evaluation results were compared with that of technique of order preference similarity to the ideal solution (TOPSIS), finding that evaluation results of cloud model were consistent with that of TOPSIS method. The cloud model realizes the transformation from qualitative evaluation to quantitative evaluation, which overcome insufficiencies of traditional evaluation methods in considering fuzziness and randomness. Results showed that during the period of 2008-2017, the state of WRCC in Guiyang was improving year by year, increasing from the serious overload carrying capacity level in 2008 to the strong carrying capacity level in 2017 (serious overload-overload-critical-weak carrying capacity-strong carrying capacity). However, some certain evaluation indicators are still in danger situation, such as population natural growth rate and use of the fertilizer per unit cultivated area, which needs to be further enhanced and improved. Moreover, the contradiction among economic development, population growth, and water resources is becoming increasingly apparent. To ensure the effective utilization of water resources in Guiyang, reasonable policies and measures should be formulated and put into effect. Research results could provide certain reference for the sustainable development of regional water resources.


Identification and characterization of the Cucurbitacins, a novel class of small-molecule inhibitors of Tropomyosin receptor kinase a.
NGF-TrkA is well known to play a key role in propagating and sustaining pruritogenic signals, which form the pathology of chronic pruritus. Inhibition of NGF-TrkA is a known strategy for the treatment of pruritus. In the present paper, we describe the identification, in vitro characterization, structure-activity analysis, and inhibitory evaluation of a novel TrkA inhibitory scaffold exemplified by Cucurbitacins (Cus). Cus were identified as TrkA inhibitors in a large-scale kinase library screen. To obtain structural models of Cus as TrkA inhibitors, AutoDock was used to explore their binding to TrkA. Furthermore, PC12 cell culture systems have been used to study the effects of Cus and traditional Chinese medicinal plants (Tian Gua Di and bitter gourd leaf) extracts on the kinase activity of TrkA. Cus block the phosphorylation of TrkA on several tyrosine sites, including Tyr490, Tyr674/675, and Tyr785, and inhibit downstream Akt and MAPK phosphorylation in response to NGF in PC12 cell model systems. Furthermore, traditional Chinese medicinal plants (Tian Gua Di and bitter gourd leaf) containing Cu extracts were shown to inhibit the phosphorylation of TrkA and Akt. These data reveal mechanisms, at least partly, of the anti-pruritus bioactivity of Cus. Taken together, with the recent discovery of the important role of TrkA as a therapeutic target, Cus could be the basis for the design of improved TrkA kinase inhibitors, which could someday help treat pruritus.


The associations of particulate matter short-term exposure and serum lipids are modified by vitamin D status: A panel study of young healthy adults.
Particulate matter (PM) exposure is associated to the adverse change in blood lipids. Vitamin D is beneficial to lipid metabolism, but whether vitamin D levels modifies the impact of air pollutants on lipids is unclear. The purpose of the study was to investigate if vitamin D modifies the associations of PM and serum lipids in young healthy people. From December 2017 to January 2018, a panel study with five once weekly follow-ups was conducted on 88 healthy adults aged 21.09 (1.08) (mean (SD)) years on average in Guangzhou, China. We measured serum lipids, serum 25-hydroxyvitamin D (25(OH)D) concentrations (440 blood samples in total), mass concentrations of particulate matter with diameters ≤2.5 μm (PM2.5), ≤1.0 μm (PM1.0), and ≤0.5 μm (PM0.5), and number concentrations of particulate matter with diameters ≤0.2 μm (PN0.2) and ≤0.1 μm (PN0.1) at each follow-up. Linear mixed-effect models were applied to assess the interaction of vitamin D and size-fractionated PM short-term exposure on four lipid metrics. We found the interactions between 25(OH)D and size-fractionated PM exposure on blood lipids in different lags (lag 3 days and 4 days). An interquartile range increase in PM2.5, PM1.0, PM0.5 were significantly associated with increments of 12.30%, 12.99%, and 13.66% in triglycerides (TGs) at lag 4 days at vitamin D levels <15 ng/mL group, respectively. Similar results were found for PN0.2, PN0.1 and low-density lipoprotein cholesterol (LDL-C). All the associations between size-fractionated PM and blood lipids were found null statistically significant in vitamin D levels ≥15 ng/mL group.


Revisiting ecological dominance in arboreal ants: how dominant usage of nesting resources shapes community assembly.
Ecologically dominant species can shape the assembly of ecological communities via altering competitive outcomes. Moreover, these effects may be amplified under limited niche differentiation. Nevertheless, the influences of ecological dominance and niche differentiation on assembly are rarely considered together. Here, we provide a novel examination of dominance in a diverse arboreal ant community, defining dominance by the prevalent usage of nesting resources and addressing how it influences community assembly. We first used a series of quantitative observational and experimental studies to address the natural nesting ecology, colony incidence on surveyed trees, and level of dominance over newly available nesting resources by our focal species, Cephalotes pusillus. The experimental studies were then used further to examine whether C. pusillus shapes assembly via an influence on cavity usage by co-occurring species. C. pusillus was confirmed as a dominant user of cavity nesting resources, with highly generalized nesting ecology, occupying about 50% of the trees within the focal system, and accounting for more than a third of new cavity occupation in experiments. Our experiments showed further that the presence of C. pusillus was associated with modest effects on species richness, but significant decreases in cavity-occupation levels and significant shifts in the entrance-size usage by co-occurring species. These results indicate that C. pusillus, as a dominant user of nesting resources, shapes assembly at multiple levels. Broadly, our findings highlight that complex interactions between a dominant species and the resource-usage patterns of other species can underlie species assembly in diverse ecological communities.


Minimally invasive facet restoration implant for chronic lumbar zygapophysial pain: 1-year outcomes.
The zygapophysial (facet) joint is the primary pain generator in one third of chronic low back pain cases. Current treatment options include temporarily palliative nonsurgical approaches, facet injections, radiofrequency denervation, and, rarely, lumbar arthrodesis. The purpose of this study was to assess the safety and effectiveness of a minimally invasive implant intended to restore facet joint function in patients with chronic lumbar facetogenic pain. This prospective, multi-center feasibility study enrolled patients with confirmed lumbar facetogenic joint pain at 1 or 2 levels who underwent at least 6 months of unsuccessful nonoperative care. Patients received a minimally invasive implant (Glyder® Facet Restoration Device, Zyga Technology, Inc., Minnetonka, MN) intended to restore facet joint function while preserving the native anatomy. Main outcomes included back pain severity using a visual analogue scale, back-specific disability using the Oswestry Disability Index (ODI), and adverse events adjudicated by an independent Clinical Events Committee. Of 40 enrolled patients, 37 patients received the facet restoration implant and 34 patients had complete 1-year follow-up data available. Over the 1-year follow-up period, back pain severity decreased 41% and ODI decreased 34%, on average. Freedom from a device- or procedure-related serious adverse event through 1 year was 84%. Implant migration was observed in 3 patients and implant expulsion from the facet joint occurred in 3 patients. In total, 2 (5.4%) patients underwent implant removal through 1 year post-treatment. A minimally invasive facet restoration implant is a promising treatment option in select patients with chronic lumbar zygapophysial pain who have exhausted nonsurgical treatments, with therapeutic benefit persisting at 1 year follow-up.


Morphological changes observed via fetal ultrasound in prenatally diagnosed and isolated congenital lymphangiomas: three case reports.
We illustrate three cases of isolated congenital lymphangioma (CL). Fetal ultrasound (US) demonstrated uniloculated cystic masses that changed to multiloculated, subcutaneous, hypoechoic, avascular cystic masses with thin septations without solid components. Case 1: CL of the right forearm; Case 2: CL of the right hypochondrium; and Case 3: CL of the left upper posterior back. Postnatal US detected multiloculated, subcutaneous, hypoechoic, avascular cystic masses with thin septations without solid components or invasive developments. We prenatally and postnatally diagnosed them as isolated CL cases due to focal, soft, bulging masses with unclear margins. Due to our correct diagnosis and precise evaluation of sizes and locations, no perinatal complications occurred. In this case series, uniloculated features changed to multiloculated features and the largest macrocyst size decreased, whereas the sizes of the smaller microcysts increased. These morphological changes observed via fetal US represent intermittent CL growing processes.


Modified laparoscopic high uterosacral ligament suspension for treatment of apical prolapse: A feasibility study.
The purpose of this study was to evaluate the feasibility of modified laparoscopic high uterosacral ligament suspension (LHUS) in women with apical prolapse who require uterine preservation. This retrospective feasibility study analyzed the demographic characteristics, procedure, and 3-year follow-up data of 23 women who underwent modified LHUS at our institution. Outcome measures included clinical and anatomical cure. Patient satisfaction was measured by the Patient Global Impression of Improvement (PGI-I). The improvement on quality of life was evaluated by pelvic floor distress inventory-short form 20 (PFDI-20). The operation time was 50 ± 17 min, the blood loss was 100 ml (50-300 ml), and the postoperative hospital stay was 3.5 days (3-6 days). At a median follow-up time of 4.3 years (3-6 years), the clinical cure rate was 91.6% and the anatomical cure rate was 87.0%. The values of Aa, Ba, C, and D points were significantly higher than those observed before operation (p < 0.05). According to PGI-I, 20 patients were satisfied, and the overall subjective satisfaction rate was 87%. The scores of PFDI-20 after operation were significantly lower than those recorded before operation (p < 0.05). Modified LHUS has the advantages of short operation time, fast postoperative recovery, low 3-year recurrence rate, and high patient satisfaction in women with apical prolapse who require uterine preservation, which is worthy of clinical promotion.


Comparison of Chronic Dysphagia in Standalone versus Conventional Plate and Cage Fusion.
Standalone cages have gained popularity because of their ease of implantation, reduced operating time, and lower profile compared with traditional plate and cage systems. The aim of this study was to compare the risk of chronic dysphagia between those who undergwent anterior cervical discectomy and fusion (ACDF) with traditional plating techniques and those who underwent standalone procedures. Between 2014 and 2015, we identified 377 consecutive patients who met the study criteria (standalone, n = 211; plate-cage, n = 166). Patient-specific characteristics and surgical characteristics were collected preoperatively. In addition, the Dysphagia Disability Index (DDI) was collected 2 years postoperatively by telephone interview. Among the patients who underwent a standalone procedure, 84% (n = 177) were available for their 2-year follow-up visit in comparison with 75% (n = 124) for plate-cage procedures. There was no statistically significant difference in postoperative DDI scores between the 2 groups, controlling for prior surgery and smoking. However, the strongest risk factors for higher DDI scores were prior cervical surgery (mean 6.0 points higher) and smoking (mean 6.2 points higher). Twenty-seven patients (8.9%) experienced chronic dysphagia. The risk was higher in the plate-cage group (n = 15, 12.1%) than in the standalone group (n = 12, 6.7%), but this difference did not reach statistical significance. Despite similar mean DDI scores, patients who undergo anterior cervical discectomy with a plate-cage may be at a higher risk for chronic dysphagia than are those with a standalone approach, but further studies with larger sample sizes are necessary to establish this relationship with greater confidence.


Discectomies of the lower cervical spine using interbody biopolymer (B.O.P.) implants. Advantages in the treatment of complicated cervical arthrosis. A review of 150 cases.
The authors report their experience with 150 cases of discectomies performed with interbody grafts using a copolymer (Biocompatible Orthopedic Polymer or BOP). Made of N-Vinylpyrrolidone-Methylmethacrylate monomers, polyamide fibres and calcium gluconate. BOP is a biocompatible, biodegradable, osteoconductive matrix, easy to use and quite safe. These properties are quite well appreciated for cervical interbody grafting. After discectomy, stabilization of the spine is immediate, and fusion slowly occurs around and through the biopolymer within one year. The biomaterial avoids morbidity inherent in the harvesting of an autograft, as well as any limitations resulting from the use of allografts.


Cis-allosteric effects of cytoplasmic Na+/K+ discrimination at varying pH. Low-affinity multisite inhibition of cytoplasmic K+ in reconstituted Na+/K(+)-ATPase engaged in uncoupled Na(+)-efflux.
In liposomes with reconstituted shark Na+/K(+)-ATPase the effect of cytoplasmic K+ was investigated in the absence of extracellular alkali ions. During such conditions the Na+/K(+)-ATPase is engaged in the so called uncoupled Na+ efflux mode in which cytoplasmic Na+ activates and binds to the enzyme and becomes translocated without countertransport of K+ as in the physiological Na+/K+ exchange mode. In this uncoupled flux mode only low-affinity inhibition by K+cyt is found to be present. The inhibition pattern is consistent with a model in which cytoplasmic K+ exhibit mixed inhibition of Na+ activation, probably by binding at the three cytoplasmic loading sites on E1ATP (E1A). With determined intrinsic binding constants for cytoplasmic Na+ to this form of KS1, KS2, KS3 = 40 mM, 2 mM, 2 mM the inhibition pattern can be simulated assuming three K+cyt sites with equal affinity for Ki = 40 mM, similar to KS1 for the first Na+cyt site. The discrimination between cytoplasmic Na+ and K+ is therefore enhanced by allosteric interaction initiated from the cis-side due to binding of the first Na+, as opposed to K+, which induces the positive cooperatively in the successive Na+ bindings. pH is found to influence the pattern of K+cyt inhibition: A lowering of the pH potentiates the K+cyt inhibition, whereas at increased pH the inhibition is decreased and transformed into a pure competitive competition.


Anesthesia for a Patient With Cerebrovascular Accident with Seizure Disorder Undergoing Medical Termination of Pregnancy: A Case Report.
The term "total intravenous anesthesia" refers to the preservation of an anesthetic plane with the use of an injectable anesthetic, a sedative that is often given in intermittent boluses. The tendency to have recurrent unprovoked seizures is known as epilepsy. Its prevalence ranges from 0.5% to 1%. The highest incidence rates are in those with anatomical or developmental brain abnormalities, as well as at the extremes of age. The most common triggering factors for epilepsy are stress and fear. The main advantage of total intravenous anesthesia is the patient's rapid recovery and early ambulatory. Conscious sedation is a strategy for giving patients excellent anesthesia and analgesia. In this case report, we will describe a high-risk epileptic patient who required conscious sedation to perform a medical termination.


The EM immunocytochemical demonstration of lysozyme in macrophage giant cells in sarcoidosis.
The giant cells (multinucleate macrophages) of human sarcoidosis have been shown by the unlabelled antibody immunoperoxidase technique at electron microscope level to contain lysozyme within cytoplasmic granules.


Senescence: A program in the road to cell elimination and cancer.
Senescence is a tumor suppressor response that prevents the proliferation of mutated cells and alert the immune system for their elimination. However, this program is not perfect and with time additional genetic and epigenetic changes can impair tumor suppression and promote cancer progression both in cell autonomous and non-cell autonomous manners. A polyploid barrier is implemented in senescent cells to further prevent cell expansion but polyploid cells can generate highly malignant tumor cells via de-polyploidization. The nuclear lamina can act as an additional fail safe to prevent cancer in these cells and drugs able to stabilize the nuclear lamina may help to treat cancers by preventing senescence escape.


Evaluation for ulnar neuropathy at the elbow in Ironman triathletes: physical examination and electrodiagnostic evidence.
Evaluation of the elbow in Ironman triathletes for ulnar compression neuropathy caused by aerobar use. Descriptive laboratory study. Ironman California 70.3, Ironman Arizona, Ironman New Orleans 70.3, San Antonio, Texas. Study 1: (n = 712) Ironman California 70.3/Ironman Arizona participants. Study 2: (n = 54) Ironman New Orleans 70.3 finishers. Study 3: (n = 11) participants training for an Ironman triathlon. Pilot questionnaire (study 1). Pilot questionnaire and prerace and postrace physical examination (study 2). Pilot questionnaire and preride and postride (and postseason) physical examination, and electrodiagnostic testing (study 3). Participants with symptoms, physical examination findings, and electrodiagnostic findings (amplitude or conduction velocity decrease) (P < 0.05). In study 1, 20.8% reported a history of ulnar symptoms. In study 2, 35.2% reported a history of ulnar symptoms. Preevent physical examination testing of the elbow showed 39.5% with positive Tinel sign and 41.5% with positive flexion/compression test. Postevent testing showed 70.4% with positive Tinel sign and 75.9% with positive flexion/compression test. In study 3, 46% reported ulnar symptoms. Preride physical examination testing showed 4.5% with positive Tinel sign and 9% with positive flexion/compression test. Postride testing showed 95.5% with positive Tinel sign and 91% with positive flexion/compression test. Postseason testing showed 64% with positive Tinel sign and 82% with positive flexion/compression test. Electrodiagnostic testing comparing preride and postride showed that ulnar nerve latency increased in 82%, amplitude decreased in 50%, and conduction velocity slowed in 64%. Electrodiagnostic testing comparing preseason and postseason showed that ulnar nerve latency increased in 73%, amplitude decreased in 64%, and conduction velocity slowed in 82%. The findings support the hypothesis of an ulnar compression neuropathy at the elbow occurring at high rates in aerobar using Ironman triathletes.


A novel series of 6-methoxy-1H-benzotriazole-5-carboxamide derivatives with dual antiemetic and gastroprokinetic activities.
A novel series of 6-methoxy-1H-benzotriazole-5-carboxamide derivatives with a medium perhydroazacycle ring in the amine moiety were prepared, and their antiemetic and gastroprokinetic activities were evaluated. Among them, N-(1-ethylhexahydroazepin-3-yl)-, N-(1-ethyloctahydroazocin-3-yl)- and N-(1-ethyloctahydroazonin-3-yl)-6-methoxy-1H-benzotriazole-5-carbo xamides (24, 36, 37) showed a potent antiemetic activity (inhibition of apomorphine-induced emesis in dogs) along with gastroprokinetic activity (gastric emptying in rats).


Sick-leave in women with alcohol dependence or abuse: effects of additional psychiatric disorders.
The study objective was to assess sick-leave among women investigated in a general population survey of alcohol dependence/abuse (ADA). A total of 399 women, selected by stratified random sampling, were interviewed and diagnosed according to DSM-III-R. Data on sick-leave were obtained by linkage with the Social Insurance records. The study found that women with ADA but without other psychiatric disorders had an increased number of annual sick-leave spells--1.82 compared with 1.47 in the reference population-whereas the mean duration was similar. Women with ADA and other psychiatric disorders had 2.38 annual spells, but also considerably longer spells (mean 16.54 days vs 9.70). Socio-economic differences were large, with the less privileged groups having both more and longer spells. Stepwise multiple regression showed that both ADA and other psychiatric disorders contributed to high sick-leave incidence and duration, as, to a lesser extent, did low education and low social group (the last variable only affected duration of the spells). The frequency of disability pension/long sickness spells was higher in women with ADA (odds ratio of 2.95). We concluded that there is a strong association between ADA and sick-leave, which increases considerably in the presence of additional psychiatric disorders.


Renal Protection and Safety of Sodium-glucose Cotransporter-2 Inhibitors in Chronic Kidney Disease.
Chronic kidney disease (CKD) has a clinical characteristic of progressive loss of kidney function and becomes a serious health and social concern. SGLT2i (sodium-glucose cotransporter 2 inhibitors), a class of anti-diabetic medications, are shown to reduce cardiovascular and renal events. This systematic review and meta-analysis aimed to assess whether SGLT2i could become a new treatment strategy for CKD for its renal protection and safety. Based on predetermined criteria, a bibliographical search was performed on May 31, 2022, by searching the following databases: ISI Web of Science, Embase, PubMed, and the Cochrane Library. Statistical analysis was conducted to assess renal protection and safety of SGLT2i by using Cochrane Review Manager Version 5.3. Thirty randomised controlled trials fulfilled the inclusion criteria and were eligible for this meta-analysis. Our study found that the SGLT2i can sustainably reduce the urine albumin/creatinine ratio (UACR) at different time points and prevent the progression to macroalbuminuria. Before 24 weeks, SGLT2i can decrease the estimated glomerular filtration rate (eGFR) compared to the control group. Interestingly, after 24 weeks, SGLT2i can continuously maintain the increase in eGFR when compared with the control group. Furthermore, SGLT2i can reduce the event rates of incident or worsening nephropathy, a decline in estimated eGFR of ≥ 50%, doubling of serum creatinine level, acute renal failure and renal failure. Interestingly, the renoprotective effects of SGLT2i are independent of its glycemic effects. SGLT2i can reduce the morbidity rate of any related adverse events, any related severe adverse events and SGLT2i have not increased the event rates of urinary tract infection, bone fractures, amputation, and acute pancreatitis when compared with the control group. SGLT2i can protect renal function and are safe drug for CKD. SGLT2i are promising therapeutic agents for CKD patients.


A complete case of Cantrell's Pentalogy with isolated left ventricular diverticulum.
The congenital left ventricular diverticulum is a rare cardiac malformation, and it may associate with Cantrell's Pentalogy with other cardiac defects. However, isolated ventricular diverticulum without any other cardiac defect in complete Cantrell's syndrome is very rare. We describe a 6-year-old male patient with a complete Cantrell's syndrome with isolated left ventricular diverticulum.


Active inference leads to Bayesian neurophysiology.
The neuronal substrates that implement the free-energy principle and ensuing active inference at the neuron and synapse level have not been fully elucidated. This Review considers possible neuronal substrates underlying the principle. First, the foundations of the free-energy principle are introduced, and then its ability to empirically explain various brain functions and psychological and biological phenomena in terms of Bayesian inference is described. Mathematically, the dynamics of neural activity and plasticity that minimise a cost function can be cast as performing Bayesian inference that minimises variational free energy. This equivalence licenses the adoption of the free-energy principle as a universal characterisation of neural networks. Further, the neural network structure itself represents a generative model under which an agent operates. A virtue of this perspective is that it enables the formal association of neural network properties with prior beliefs that regulate inference and learning. The possible neuronal substrates that implement prior and posterior beliefs and how to empirically examine the theory are discussed. This perspective renders brain activity explainable, leading to a deeper understanding of the neuronal mechanisms underlying basic psychology and psychiatric disorders in terms of an implicit generative model.


Long-Term Outcomes of Cochlear Implantation in Irradiated Ears of Nasopharyngeal Carcinoma Patients.
To evaluate the safety and feasibility of cochlear implantation (CI) in irradiated ears of nasopharyngeal carcinoma (NPC) patients. A retrospective study. From 2008 to 2017, 10 adults with binaural severe or profound sensorineural hearing loss subsequent to radiotherapy for NPC underwent CI in our center. The mean follow-up was 63.2 months. Hearing and speech performance were evaluated pre- and postoperatively with audiometric and speech discrimination testing, Category of Auditory Performance, Speech Intelligibility Rating, and Chinese version of Nijmegen Cochlear Implant Questionnaire. According to the severity of radioactive osteomyelitis of temporal bone, patients were classified into three categories: mild, moderate, and severe. Patients in mild category underwent routine CI. Patients in moderate category underwent extended radical mastoidectomy and CI simultaneously. Patients in severe category underwent subtotal temporal bone resection, external auditory canal elimination, and CI simultaneously or by stage. There was no massive hemorrhage, facial paralysis, or nonunion of incision after operation. One suffered from radiation encephalopathy 13 months postoperatively; since then, the cochlear implant has been idle. The other nine patients demonstrated encouraging results of hearing and speech performance. CI for postirradiated ears of NPC is safe and feasible. Strict control of operative indications and extra care during surgery are required. Individual surgical plan should be made according to the severity of radioactive osteomyelitis. Choose one-stage surgery as much as possible in severe cases to avoid the risk of difficulty in locating round window in second-stage surgery. 4 Laryngoscope, 131:649-655, 2021.


Inhibition of mammary tumorigenesis in GR mice with 2-bromo-alpha-ergocryptine.
A high incidence of mammary tumors is found in multiparous GR mice during the 2nd and 3rd pregnancies and in nulliparous GR mice treated with estrone/progesterone. The purpose of this study was to determine if prolactin is a contributing hormone in the genesis of these neoplasms. In one series of experiments, 238 15-week-old nulliparous GR mice were treated with estrone (drinking water, 0.5 mg/liter) plus progesterone (30 mg progesterone pellet with cholesterol, implanted SC once monthly) for a period of 13 weeks. Half of these mice were injected SC once daily with 100 micrograms of the prolactin-suppressing drug 2-bromo-alpha-ergocryptine (CB-154) for the duration of hormone treatment, and the other half were injected SC once daily with 0.9% NaCl solution (controls). In another series of experiments, 87 pregnant GR mice were divided into two groups and injected SC once daily from day 7 to 21 of pregnancy with 0.9% NaCl solution (controls) or CB-154 (100 micrograms/mouse). In the first series, the numbers of mice with mammary tumors and total number of mammary tumors were: controls, 58/119 (49%) and 73; CB-154 treatment, 34/119 (29%) and 37, respectively. In the second series, the numbers were: controls, 39/44 (89%) and 73; CB-154 treatment, 24/43 (56%) and 43, respectively. In both studies, CB-154 treatment significantly (p less than 0.05-0.005) reduced the percentage of mice with mammary tumors and total number of mammary tumors. These results provide evidence that prolactin is a contributing hormone in the genesis of estrone/progesterone and pregnancy-induced mammary tumors in female GR mice.


Anti-M causing delayed hemolytic transfusion reaction.
A 52-year-old gravida 1, para 1 woman with M- red cells experienced a delayed hemolytic transfusion reaction and exhibited an anti-M antibody following the infusion of four units of M+ red cells. Measurements of erythrocyte survival using 51Cr-labeled donor M+ and M- red cells and in vitro studies of monocyte-macrophage phagocytosis of sensitized reagent red cells implicate anti-M in the pathogenesis of hemolysis.


Is stomatal conductance in a tomato crop controlled by soil or atmosphere?
The effects of soil water deficits and air vapour pressure deficits on stomatal conductance of tomato leaves were analysed separately under field conditions in central Portugal. Three conditions were created: low soil and air humidity (A), high soil and air humidity (B) and low soil but high air humidity (C). The results show that the effect of air vapour pressure deficit on stomatal behaviour is more important than the effect of soil water deficit when the predawn leaf water potential is above -0.4 MPa.


Dietary polysaccharides from guavira pomace, a co-product from the fruit pulp industry, display therapeutic application in gut disorders.
Inflammatory bowel disease (IBD) includes two distinct diseases: Crohn's disease (CD) and ulcerative colitis (UC). IBD is a chronic systemic disease of the gastrointestinal tract, characterized by an inflammatory process. The mechanisms by which diseases develop are still unknown, but it is known that it results from a complex interaction between genetic variability, the host's immune system, and environmental factors. One of the main complaints of patients is abdominal pain, which may be associated with the release of inflammatory mediators, changes in the normal motility of the digestive tract, and increased intestinal permeability. Currently available drugs for abdominal pain are not satisfactory, therefore, it is extremely necessary to seek new therapeutic options for the treatment of abdominal pain. Polysaccharides extracted from fruits have attracted interest, as these molecules protect the intestinal mucosa and promote wound healing, attenuating inflammation, pain, and altered intestinal motility. In this study, we investigated the ability of pectic polysaccharides obtained from guavira pomace, named CPW to reduce visceral hypersensitivity, regulate intestinal motility, and control diarrhea in mice. Acetic acid, capsaicin, or mustard oil were used to assess visceral pain in normal mice. CPW reduced abdominal writhing, cell migration, and capsaicin-induced visceral nociception. Furthermore, it regulated intestinal motility and all measured parameters of castor oil-induced diarrhea. CPW treatment reversed the increase in mucosal permeability, TEER, and tissue weight caused by acetic acid. In addition, molecular docking analysis showed that specific the CPW units binds to the 3N8V, 5COX, 2J67 and 6RBF proteins. Thus, the results suggest that CPW has attractive therapeutic characteristics for the treatment of abdominal pain and ulcerative colitis.


Cross-sectional Characterization of SARS-CoV-2 Antibody Levels and Decay Rates Following Infection of Unvaccinated Elderly Individuals.
SARS-CoV-2 infections have disproportionally burdened elderly populations with excessive mortality. While several contributing factors exists, questions remain about the quality and duration of humoral antibody-mediated responses resulting from infections in unvaccinated elderly individuals. Residual serum/plasma samples were collected from individuals undergoing routine SARS-CoV-2 polymerase chain reaction testing in a community laboratory in Canada. The samples were collected in 2020, before vaccines became available. IgG, IgA, and IgM antibodies against SARS-CoV-2 nucleocapsid, trimeric spike, and its receptor-binding domain were quantified via a high-throughput chemiluminescent enzyme-linked immunosorbent assay. Neutralization efficiency was also quantified through a surrogate high-throughput protein-based neutralization assay. This study analyzed SARS-CoV-2 antibody levels in a large cross-sectional cohort (N = 739), enriched for elderly individuals (median age, 82 years; 75% >65 years old), where 72% of samples tested positive for SARS-CoV-2 by polymerase chain reaction. The age group ≥90 years had higher levels of antibodies than that <65 years. Neutralization efficiency showed an age-dependent trend, where older persons had higher levels of neutralizing antibodies. Antibodies targeting the nucleocapsid had the fastest decline. IgG antibodies targeting the receptor-binding domain remained stable over time, potentially explaining the lack of neutralization decay observed in this cohort. Despite older individuals having the highest levels of antibodies postinfection, they are the cohort in which antibody decay was the fastest. Until a better understanding of correlates of protection is acquired, along with the protective role of nonneutralizing antibodies, booster vaccinations remain important in this demographic.


Stalled replication fork rescue requires a novel DNA helicase.
During DNA replication, forks often stall and require restart. One mechanism for restart requires that the fork be moved in a direction opposite to that of replication. This reaction is known as fork regression. For this reaction to occur, the enzyme must couple unwinding of the nascent heteroduplex fork arms to the rewinding of nascent strands ahead of itself and to the parental duplex in its wake. As the arms of the fork are complementary, this reaction is isoenergetic making it challenging to study. To overcome this, a novel adaptation of magnetic tweezers was developed by the Croquette group. Here, a 1200bp hairpin was attached at opposite ends to a flow cell surface and a magnetic bead. By manipulating the bead with the magnets, force can be applied to unwind the hairpin or alternatively, released to allow the hairpin to rewind. This adaptation was used to study fork regression by RecG. The results show that this is an efficient regression enzyme, able to work against a large opposing force. Critically, it couples DNA unwinding to duplex rewinding and in the process, can displace bound proteins from fork arms.


Transcriptional responses and mechanisms of copper nanoparticle toxicology on zebrafish embryos.
Copper nanoparticles (CuNPs) are used widely due to their attractive antimicrobial properties. However, their biosafety and kinetics on vertebrate embryogenesis are still limited. In this study, CuNPs were revealed to induce eye hypoplasia and almost no digestive gut in zebrafish embryos in a dose-dependent manner. Then, transcriptional responses of zebrafish embryos to CuNPs were investigated, and it was revealed that the genes related to wound healing and stimulus responses were up-regulated, but the genes associated with phototransduction and metabolisms were down-regulated. Differentially expressed genes (DEGs) in CuNPs-exposed and Cu2+-exposed embryos were compared further. Increased VEGF signaling and expression of fli1 were observed in CuNPs rather than Cu2+ treated embryos, but increased reactive oxygen species (ROS) and the resulting enhanced hemoglobin were observed in both CuNPs and Cu2+ treated embryos. This study for the first time revealed that CuNPs and Cu2+ both down-regulated the genes related to phototransduction and metabolisms, but up-regulated the genes associated with hemoglobin. Additionally, compared with Cu2+, CuNPs might be more effective in elevating blood vessels in embryos. Our results suggest that the biological effects of CuNPs are organogenesis-specific during fish embryogenesis, and both particles and ions might mediate their biological effects on embryogenesis.


Multivalent binding of the hub protein LC8 at a newly discovered site in 53BP1.
Tumor suppressor p53 binding protein 1 (53BP1) is a scaffolding protein involved in poly-ADP ribose polymerase inhibitor hypersensitivity in BRCA1-negative cancers. 53BP1 plays a critical role in the DNA damage response and relies on its oligomerization to create foci that promote repair of DNA double-strand breaks. Previous work shows that mutation of either the oligomerization domain or the dynein light chain 8 (LC8)-binding sites of 53BP1 results in reduced accumulation of 53BP1 at double-strand breaks. Mutation of both abolishes focus formation almost completely. Here, we show that, contrary to current literature, 53BP1 contains three LC8-binding sites, all of which are conserved in mammals. Isothermal titration calorimetry measuring binding affinity of 53BP1 variants with LC8 shows that the third LC8-binding site has a high affinity and can bind LC8 in the absence of other sites. NMR titrations confirm that the third site binds LC8 even in variants that lack the other LC8-binding sites. The third site is the closest to the oligomerization domain of 53BP1, and its discovery would challenge our current understanding of the role of LC8 in 53BP1 function.


Effect of mildly elevated thyroid-stimulating hormone during the first trimester on adverse pregnancy outcomes.
To investigate the effect of a mildly elevated thyroid-stimulating hormone (TSH) concentration between 2.5 and 4.0 mIU/L during the first trimester on pregnancy outcomes in thyroid peroxydase antibody (TPOAb)-negative pregnant women. A total of 1858 pregnant women who were TPOAb-negative before 13+ 6 gestational weeks, received regular prenatal services, and delivered in the third affiliated hospital of Sun Yat-Sen University were recruited from June 2016 to June 2017. Measurements of thyroid function (TSH, free T4 [FT4] and TPOAb) and adverse pregnancy outcomes were assessed and recorded. Among the 1858 study participants, the 97.5th percentile for TSH was 3.76 mIU/L, and 142 women (7.6%) had mildly elevated TSH levels between 2.5 and 4.0 mIU/L. No differences in the incidence of adverse pregnancy outcomes were observed between patients with a mildly elevated TSH level and those with a normal TSH level (< 2.5 mIU/L). A mildly elevated TSH concentration (2.5-4.0 mIU/L) during the first trimester of pregnancy in TPOAb-negative women was not associated with adverse pregnancy outcomes in our study population. Accordingly, it may be possible to raise the upper limit of the healthy TSH reference range for pregnant women.


Comparison of dynamic properties of canal-evoked vestibulospinal reflexes of the neck and forelimb in the decerebrate cat.
The responses of neck and forelimb muscles to sinusoidal polarization of the horizontal canal nerve were compared by recording from these muscles simultaneously. Contrary to results on the vestibulocollic reflex, the central phase lag in the vestibulo-forelimb reflex increases with increasing frequencies up to 3 Hz. This demonstrates a difference in the organization of vestibular-driven pathways to neck and forelimb muscles.


Treatment of Kimura disease with photodynamic therapy: a case study.
We report on the application of photodynamic therapy (PDT) in the management of Kimura disease. A 58-year-old Asian male was offered this modality to assess the possibility to control disease progression. The patient was managed with surgery and the disease recurred and caused facial disfigurement. PDT was offered after careful discussion at UCLH multidiscipline meeting. The photosensitiser "mTHPC" was introduced intravenously 96h prior to delivering the light under ultrasound guidance. Magnetic resonance images showed moderate-significant reduction of the disease volume. Fourteen months post-PDT, the disease started re-growing and the patient subsequently underwent one further round of PDT which was as successful as the first round in reducing the facial disfigurement. Photodynamic therapy was very effective in controlling disease progression in this patient who suffers from Kimura disease.


Renal ultrasonography should be done routinely in children with first urinary tract infections.
To assess the consequences of renal ultrasonography (RUS) in the treatment of children younger than 5 years of age with a first febrile urinary tract infection. We retrospectively reviewed the results of imaging studies, including RUS, computed tomography, and voiding cystourethrography in children with a first febrile urinary tract infection during a 2-year period. Children with known urologic anomalies, other underlying diseases, or simultaneous combined illnesses were excluded. Children with nephromegaly were diagnosed with acute lobar nephronia by computed tomography. A total of 390 children were included in this study. Of the 390 children, 112 (28.7%) had abnormal RUS findings. The children with abnormal RUS findings of nephromegaly, small kidney, intermittent hydronephrosis, or a double collecting system had a significantly greater incidence of vesicoureteral reflux than children with normal RUS findings. Additionally, the occurrence of high-grade vesicoureteral reflux in children with abnormal RUS findings was more frequent than in children with normal RUS findings. The results of our study indicate that it is worth performing RUS in children with a first febrile urinary tract infection because abnormal kidney size or other specific structural ultrasound findings should be investigated, in addition to isolated hydronephrosis.


Decreased expression and role of GRK6 in spinal cord of rats after chronic constriction injury.
Nerve injury and inflammation can both induce neuropathic pain via the production of pro-inflammatory cytokines. In the process, G protein-coupled receptors (GPCRs) were involved in pain signal transduction. GPCR kinase (GRK) 6 is a member of the GRK family that regulates agonist-induced desensitization and signaling of GPCRs. However, its expression and function in neuropathic pain have not been reported. In this study, we performed a chronic constriction injury (CCI) model in adult male rats and investigated the dynamic change of GRK6 expression in spinal cord. GRK6 was predominantly expressed in the superficial layers of the lumbar spinal cord dorsal horn neurons and its expression was decreased bilaterally following induction of CCI. The changes of GRK6 were mainly in IB4 and P substrate positive areas in spinal cord dorsal horn. And over-expression of GRK6 in spinal cord by lentivirus intrathecal injection attenuated the pain response induced by CCI. In addition, the level of TNF-α underwent the negative pattern of GRK6 in spinal cord. And neutralized TNF-α by antibody intrathecal injection up-regulated GRK6 expression and attenuated the mechanical allodynia and heat hyperalgesia in CCI model. All the data indicated that down-regulation of neuronal GRK6 expression induced by cytokine may be a potential mechanism that contributes to increasing neuronal signaling in neuropathic pain.


UV-specific DNA repair recombinant fusion enzyme: a new stable pharmacologically active principle suitable for photoprotection.
UV radiation can produce mutations in skin cells and correlates strongly with the onset of actinic keratoses and basal and squamous cell carcinomas. Xeroderma pigmentosum (XP) is a heritable disease characterized by an extreme sensitivity of skin to UV radiation. Recently, studies in cultured cells as well as in XP patients have demonstrated that the recombinant T4 endonuclease V UV-specific endonuclease could enhance repair of UV-induced photoproducts. We aimed to obtain a stable UV-specific DNA recombinant endonuclease, pharmacologically active in mammalian cells so as to be used in treatment and prophylaxis of sun damage. The UV-specific DNA endonuclease gene obtained from Micrococcus luteus, was fused to a leader peptide and expressed (alphaUveA), refolded and purified. A construction under the control of an eukaryotic promoter was used to transfect XP fibroblasts deficient in DNA damage repair. Transformed cells were UV irradiated and cell survival was assessed. alphaUveA was obtained as a highly active UV-specific repair enzyme stable for at least 2 years. XP fibroblasts transfected with alphaUveA gene increased the resistance to UV radiation and, in consequence, cell survival. alphaUveA is stable and pharmacologically active in human cells. The topical administration of this long-term stable new active principle could help diminish the risks of skin cancer after sun exposure.


Dynamic mechanical analysis with portable NMR.
Dynamic mechanical analysis (DMA) is an umbrella term for a variety of rheological experiments in which the response of a sample subjected to an oscillatory force is measured to characterize its dynamic properties. In this work, we present a method for DMA that employs a small unilateral three magnet array with an extended constant gradient to measure the velocity of a vibrating sample. By orienting the vibrations in the direction of the gradient, we use the motion-sensitized phase accumulation to determine the velocity. By implementing delays into the pulse sequence, we measure the phase at evenly spaced points in the vibration cycle, allowing for the acquisition of a complete velocity waveform. Using velocity waveforms, samples are characterized through differences in amplitude and phase, providing information on the magnitude of the dynamic modulus and loss-angle, respectively.


Early stool microbiome and metabolome signatures in pediatric patients undergoing allogeneic hematopoietic cell transplantation.
The contribution of the gastrointestinal tract microbiome to outcomes after allogeneic hematopoietic cell transplantation (HCT) is increasingly recognized. Investigations of larger pediatric cohorts aimed at defining the microbiome state and associated metabolic patterns pretransplant are needed. We sought to describe the pretransplant stool microbiome in pediatric allogenic HCT patients at four centers. We performed shotgun metagenomic sequencing and untargeted metabolic profiling on pretransplant stool samples. Samples were compared with normal age-matched controls and by clinical characteristics. We then explored associations between stool microbiome measurements and metabolite concentrations. We profiled stool samples from 88 pediatric allogeneic HCT patients, a median of 4 days before transplant. Pretransplant stool samples differed from healthy controls based on indices of alpha diversity and in the proportional abundance of specific taxa and bacterial genes. Relative to stool from healthy patients, samples from HCT patients had decreased proportion of Bacteroides, Ruminococcaeae, and genes involved in butyrate production, but were enriched for gammaproteobacterial species. No systematic differences in stool microbiome or metabolomic profiles by age, transplant indication, or hospital were noted. Stool metabolites demonstrated strong correlations with microbiome composition. Stool samples from pediatric allogeneic HCT patients demonstrate substantial dysbiosis early in the transplant course. As microbiome disruptions associate with adverse transplant outcomes, pediatric-specific analyses examining longitudinal microbiome and metabolome changes are imperative to identify causal associations and to inform rational design of interventions.


Effect of Calcium and Manganese Supplementation on Heat Resistance of Spores of Bacillus Species Associated With Food Poisoning, Spoilage, and Fermentation.
Bacterial spores often survive thermal processing used in the food industry, while heat treatment leads not only to a decrease in the nutritional and organoleptic properties of foods, but also to a delay in fermentation of fermented foods. Selective reduction of undesirable spores without such impediments is an ongoing challenge for food scientists. Thus, increased knowledge of the spore-forming bacteria is required to control them. In this study, the heat resistance results (D 100 ° C) of the spores of four Bacillus species were determined and compared to previous literature, and found that B. cereus has significantly lower heat resistance than the other Bacillus species, B. coagulans, B. subtilis, and B. licheniformis. Using the spores of these strains, this study also evaluated the effects of single and combined supplementation of calcium (0.00-2.00 mM) and manganese (0.00-0.50 mM) on heat resistance (D 100 ° C). The results revealed that the spores of B. licheniformis and B. cereus displayed the smallest heat resistance when sporulated on media rich in calcium. Conversely, B. coagulans spores and B. subtilis spores exhibited the greatest heat resistance when sporulated under calcium-rich conditions. The opposite results (stronger heat resistance for B. licheniformis spores and B. cereus spores, and smaller heat resistance for B. coagulans spores and B. subtilis spores) were obtained when the spores were formed on media poor in the minerals (particularly calcium). Based on the results, the Bacillus species were divided into two groups: B. licheniformis and B. cereus; and B. coagulans and B. subtilis. The study provides valuable insight to selectively reduce spores of undesirable Bacillus species in the food industry.


Triton X-100 promotes the accumulation of phosphatidic acid and inhibits the synthesis of phosphatidylcholine in human decidua and chorion frondosum tissues in vitro.
Triton X-100 is known to affect phospholipid metabolism and the generation of various signal molecules from cellular phospholipids. In the present work the effect of Triton X-100 on phospholipid metabolism of human decidua and of the primordial placenta (chorion frondosum) was studied. Triton X-100 (0.05%, v/v) added to tissue mince 30 min before the end of a 60 min incubation stimulated 2-4-fold (decidua) and 4-6-fold (placenta) the incorporation of [32P]phosphate ([32P]Pi) into phosphatidic acid, while markedly decreasing the labeling of phosphatidylcholine. Triton X-100 had no effect on the labeling of phosphatidylinositol in the decidua, and only a slight increase was observed in the placenta. When labeled glucose was used to assess phospholipid synthesis, the addition of Triton had no effect on phosphatidic acid, while decreasing the synthesis of phosphatidylcholine. Incorporation of [32P]Pi into phosphatidic acid was not accelerated by a submicellar concentration (0.01%) of Triton, whereas the synthesis of phosphatidylcholine was decreased irrespective of detergent concentration. Anionic or cationic detergents could not mimic the action of Triton on phosphatidic acid synthesis. Although Triton inhibited the synthesis of ATP in a dose-dependent manner, this could not account for the above results. Instead, it is suggested that diacylglycerol kinase and phosphocholine:CTP cytidylyltransferase are possible targets of the action of Triton X-100.


Buffer species-dependent catalytic activity of Cu-Adenine as a laccase mimic for constructing sensor array to identify multiple phenols.
Laccase mimics are multicopper oxidase highly important for biotechnology and environmental evaluation/remediation. However, buffer species-dependent catalytic activity is rarely investigated. Herein, through Cu2+ coordinating with adenine (A), gram-scale Cu-Adenine nanosheets are synthesized. As a laccase mimic, Cu-Adenine exhibits excellent catalytic performance in 10 mM Tris-HAc, and greatly decreases in 10 mM MES (4-morpholine ethanesulfonic acid) and further decreases in 10 mM HEPES (N-2-hydroxyethyl piperazine-N'-2-ethanesulfonic acid) (pH = 7, 25 °C). Moreover, upon gradually increasing NaCl to 500 mM, the catalytic activity further enhances. Such the buffer species/NaCl concentration-dependent catalytic activity is explained with the help of Km (Michaelis constant) and Vmax (maximum rate value) Based on the fact that Cu-Adenine could differentially catalyze phenolic substrates (2,4-dichlorophenol (2,4-DP), o-chlorophenol (o-CP), m-chlorophenol (m-CP), p-chlorophenol (p-CP), phenol and catechol), a colorimetric sensor array with three buffer solutions as sensing channels is designed for simultaneously discriminating 2,4-DP, o-CP, m-CP, p-CP, phenol and catechol as low as 10 μM, even quantifying 2,4-DP (as a model analyst). The performance is further validated through accurately identifying binary and ternary mixtures, and even 18 blind samples containing one of six phenols and ternary mixtures. Finally, the designed sensor array is successfully applied for identifying six representative phenols in various simulated water samples, presenting great potential and valuable applications for large-scale scanning levels of phenols in water samples.


Extracellular signal-regulated kinases (ERK) and protein kinase C (PKC) activities are involved in the modulation of Nur77 and Nor-1 expression by dopaminergic drugs.
The dopamine system is the main target of antipsychotic and psychostimulant drugs. These drugs induce intracellular events that culminate in the transcription of immediate early genes, such as c-fos. Another class of transcription factors, namely, the nuclear receptor subgroup called Nurs (Nur77, Nurr1 and Nor-1), has recently been associated with behavioral and biochemical effects mediated by dopamine. However, the signaling cascade leading to modulation of Nur mRNA levels in the brain has never been investigated. In the present study, we explore in vivo using specific kinase inhibitors the role of mitogen-associated and extracellular signal-regulated kinases (MEK) and protein kinase C (PKC) in the modulation of Nur expression induced by dopamine receptor drugs. Modulation of Nur77 expression by a dopamine D(2) receptor antagonist is associated with MEK and PKC activities, whereas only the PKC activity participates in the modulation of Nor-1 expression. Both MEK and PKC activities also participate in the modulation of Nur77 mRNA levels induced by dopamine receptor agonists, whereas a selective MEK activity is associated with the modulation of Nor-1 mRNA levels. Interestingly, modulation of dopamine drug-induced locomotor activities by kinase inhibitors is in accordance with the effects on Nur77, but not Nor-1, expression. Taken together, the results indicate that signaling events leading to modulation of Nur77 and Nor-1 expression following dopamine receptor interacting drugs are distinct. Considering that orphan nuclear receptors of the Nur subgroup display an important ligand-independent constitutive activity, characterization of the signaling cascades involved in the regulation of their expression represents an important step for understanding their role in dopamine system physiology and pathophysiology.


Differential release of enkephalin and enkephalin-containing peptides from perfused cat adrenal glands.
We have compared the enkephalin-like material derived from proenkephalin released from perfused cat adrenal glands stimulated with pilocarpine (5 X 10(-4)M) and nicotine (5 X 10(-6) M). In addition, two doses of acetylcholine (10(-5) and 10(-4) M) and 50 mM K+ were tested. Free Met-enkephalin immunoreactivity and total Met-enkephalin immunoreactivity, as determined by enzymatic digestion of large enkephalin-containing fragments, were coreleased with catecholamines. Free Met-enkephalin immunoreactivity represented 13% of total immunoreactivity for nicotinic stimulation, 46% for pilocarpine, 33% for 10(-5) M acetylcholine, 22% for 10(-4) M acetylcholine, and 16% for 50 mM K+. Analysis of the perfusate by gel filtration showed that 80% of the total Met-enkephalin immunoreactivity whose release was induced by pilocarpine was eluted in fractions corresponding to fragments of low molecular weight, whereas these fractions accounted only for 10% of the total Met-enkephalin immunoreactivity whose release was induced by nicotine. HPLC analysis of low-molecular-weight peptide fractions revealed that Met-enkephalin, Met-enkephalin-Arg-Gly-Leu, and Met-enkephalin-Arg-Phe represented 69% of total Met-enkephalin immunoreactivity whose release was induced by pilocarpine. These results indicate that selective activation of muscarinic receptors is followed by release of low-molecular-weight material, whereas nicotine application also yielded high-molecular-weight peptides. Furthermore, increasing the acetylcholine concentration from 10(-5) to 10(-4) M and using 50 mM K+ increased proportionally the high-molecular-weight peptide secretion. Results are discussed in relation to the existence of a heterogeneous population of granules either in the same cell or in different cells, containing proenkephalin-derived peptides. (ABSTRACT TRUNCATED AT 250 WORDS)


Lack of association between febrile seizures and vaccines containing diphtheria, tetanus, and acellular pertussis in Chinese children.
The association between the administration of vaccines containing diphtheria, tetanus, and acellular pertussis (DTaP) and febrile seizures (FSs) is unclear. This study aimed to evaluate the risk of FSs after the administration of DTaP-containing vaccines in Chinese children aged 1 to 23 months. A self-controlled case series (SCCS) design was adopted based on data from the Ningbo Regional Health Information Platform (NRHIP). The observation period was from 1 to 23 months of age. The relative incidences (RIs) within 0 to 3 days, 4 to 7 days, and 0 to 7 days after the administration of DTaP-containing vaccines were estimated. The remaining observation period was the control period. The RIs within 0 to 3 days, 4 to 7 days, and 0 to 7 days after any dose of DTaP-containing vaccines were 1.14 (95% CI 0.86 to 1.52), 0.89 (95% CI 0.65 to 1.23), and 1.02 (95% CI 0.82 to 1.26), respectively. This study provides reassuring evidence that there is no increased risk of FSs immediately after the administration of DTaP-containing vaccines, which might serve to reassure both professionals and families with regard to the risk of FSs associated with DTaP-containing vaccines.


Predicting Postoperative Mortality After Metastatic Intraspinal Neoplasm Excision: Development of a Machine-Learning Approach.
Mortality following surgical resection of spinal tumors is a devastating outcome. Naïve Bayes machine learning algorithms may be leveraged in surgical planning to predict mortality. In this investigation, we use a Naïve Bayes classification algorithm to predict mortality following spinal tumor excision within 30 days of surgery. Patients who underwent laminectomies between 2006 and 2018 for excisions of intraspinal neoplasms were selected from the National Surgical Quality Initiative Program. Naïve Bayes classifier analysis was conducted in Python. The area under the receiver operating curve (AUC) was calculated to evaluate the classifier's ability to predict mortality within 30 days of surgery. Multivariable logistic regression analysis was performed in R to identify risk factors for 30-day postoperative mortality. In total, 2094 spine tumor surgery patients were included in the study. The 30-day mortality rate was 5.16%. The classifier yielded an AUC of 0.898, which exceeds the predictive capacity of the National Surgical Quality Initiative Program mortality probability calculator's AUC of 0.722 (P < 0.0001). The multivariable regression indicated that smoking history, chronic obstructive pulmonary disease, disseminated cancer, bleeding disorder history, dyspnea, and low albumin levels were strongly associated with 30-day mortality. The Naïve Bayes classifier may be used to predict 30-day mortality for patients undergoing spine tumor excisions, with an increasing degree of accuracy as the model better performs by learning continuously from the input patient data. Patient outcomes can be improved by identifying high-risk populations early using the algorithm and applying that data to inform preoperative decision making, as well as patient selection and education.