[Surgical treatment of aortopulmonary septal defect].
To study the surgical treatment of aortopulmonary septal defect. From January 1983 to December 1996, 5 patients with aortopulmonary septal defect (APSD) (2 male and 3 female) aged from 6 to 34 years (mean 17.4 years) underwent surgical treatment. According to Mori's were classification, 5 patients belonged to type I, 2 type II and 1 type III. The diameters of the defect ranged from 1.0 to 3.0 cm. The operations were performed under moderate hypothermic cardiopulmonary bypass. Pulmonary artery incision was performed, in 3 patients while aortic incision in the other 2. All defects were repaired by Dacron patch. There were no operative deaths and postoperative complications. During follow-up of 10 months to 12 years, no late complications and deaths were found. The operation should be done early as possible whenever the diagnosis is established. The surgical repair should be taken under cardiopulmonary bypass. To chose an incision on the aorta is more reasonable than on the pulmonary artery. The use the dacron patch can prevent stenosis and recanalization after operation.


Modulation of Cardiometabolic Disease Markers by Type I Interferon Inhibition in Systemic Lupus Erythematosus.
Neutrophil dysregulation and the type I interferon (IFN) axis have been proposed to contribute to premature cardiovascular disease, a leading cause of mortality in patients with systemic lupus erythematosus (SLE). In the present study, we evaluated the ability of anifrolumab, a type I IFN receptor-blocking antibody, to reduce neutrophil extracellular trap (NET) formation and modulate cardiometabolic disease markers in comparison to placebo. Study subjects comprised patients with moderate-to-severe SLE who were enrolled in phase IIb of the MUSE trial (A Phase II, Randomized Study to Evaluate the Efficacy and Safety of MEDI-546 in Subjects with Systemic Lupus Erythematosus), with healthy individuals as controls. Blood samples were collected from SLE patients (n = 305) and healthy controls (n = 10-20) before the initiation of treatment (baseline) and from SLE patients after they had been treated with 300 mg of anifrolumab (n = 99) or placebo (n = 102). Baseline IFN gene signature test status was determined, and the IFN gene signature (21-gene panel) was monitored over time. Serum proteins were measured by multiplex immunoassay or ultrasensitive Simoa assay. NET complexes, cholesterol efflux capacity (CEC), and glycoprotein acetylation (GlycA) and other lipid parameters were assessed in plasma. Formation of NET complexes and levels of tumor necrosis factor (TNF) and interleukin-10 (IL-10) were correlated with extent of type I IFN pathway activity. NET complexes and IL-10 levels were up-regulated in SLE patients compared to healthy controls (P < 0.008). The cardiometabolic disease markers CEC and GlycA were also found to be dysregulated in patients with SLE (P < 0.001 versus healthy controls). Type I IFN receptor inhibition with anifrolumab significantly reduced NET complexes and GlycA and improved CEC compared to baseline (P < 0.05) whereas no improvements were seen with placebo. Levels of TNF and IL-10 were reduced with anifrolumab compared to placebo (P < 0.05). These data support a key role for type I IFNs in modulating factors contributing to SLE vasculopathy and suggest that inhibition of this pathway could decrease cardiovascular risk in individuals with SLE.


Central serotonin-like activity of 6-chloro-2-[1-piperazinyl]-pyrazine (CPP; MK-212).
CPP, administered systemically, elicited four distinct responses characteristic of serotonin-receptor activation in the central nervous system. The crossed extensor reflex in the acutely spinalized rat was enhanced by treatment with CPP, 1-16 mg/kg. CPP, 1.11-10 mg/kg, elicited a dose-related increase in head twitches in mice. A complex motor syndrome in rats similar to that produced by pargyline plus tryptophan (or other treatments effecting increased activation of central serotonin receptors) was produced by 1.25-5 mg/kg of CPP. An increase in twitch frequency of the mylohyoideus muscle in the urethane anesthetized rat occured after CPP at 0.1 mg/kg or less. Complete abolition of all four effects of CPP was achieved by pretreatment with the centrally acting indoleamine antagonist methergoline. The peripherally acting serotonin antagonist xylamidine was ineffective or only weakly active, depending upon the test procedure, in preventing the serotonin-like actions of CPP. These findings indicate that CPP has a serotoninmimetic action in the central nervous system.


Clearance rates of bacteria-sized particles by freshwater ciliates, measured with monodisperse fluorescent latex beads.
Monodisperse fluorescent latex particles with diameters of 0.57 and 1.04 μm have been used to measure the clearance rates of bacteria-sized particles by two ciliates from a Norwegian lake. The clearance rates by Epistylis rotans on these particles were in the range 0.23 to 1.26 μl ind-1h-1, and by Strombidium sp. 0.26 to 0.90 μl ind-1 h-1. The clearance rates varied with food level and temperature. Possibilities and limitations of the suggested method are discussed.


Thymus: Conservation in evolution.
From an evolutionary point of view, the thymus is a new organ observed for the first time in fish concomitantly with the appearance of adaptive clonotypical immunity. Hormone and neuropeptide expression was demonstrated in different species suggesting a conserved role of these molecules. An integrated evolution of immune and neuroendocrine responses appears to have been realized by means of the re-use of ancestral material, such as neuroendocrine cells and mediators, to create a thymic microenvironment for the maturation and differentiation of T cells.


Nutrition beliefs, practices, and perceptions of young dancers.
Forty-nine dancers from 21 states and Mexico ages 13-20 years participated in a study designed to further explore nutrition beliefs and dietary practices of young dancers. Subjects completed a previously used questionnaire that identifies nutrition beliefs and practices. The correlation between actual height and weight and subjects' perceived height and weight was significantly different (p = less than or equal to 0.5). Subjects requested that additional nutrition education be included in their training programs.


[Manipulations of immune reactions by antigen-immunosuppressive agent-conjugates. VI. Antigen specific binding of 6-mercaptopurine-protein conjugates by lymphocytes].
The immunologic specificity of 6-mercaptopurin-protein conjugates has been determined by rosette inhibition test using antigen-stimulated lymphocytes and antigen-coated sheep erythrocytes. The specific binding of antigen-immunosuppressive agent-conjugated onto immunocompetent cells is as strong as the binding of the native antigen. The increasing aggregation of the conjugates in consequence of the higher coupling ratio and the thus increased multivalence of the antigen may compensate the effect of antigen determinant loss.


One-pot biosynthesis of 7β-hydroxyandrost-4-ene-3,17-dione from phytosterols by cofactor regeneration system in engineered mycolicibacterium neoaurum.
7β-hydroxylated steroids (7β-OHSt) possess significant activities in anti-inflammatory and neuroprotection, and some of them have been widely used in clinics. However, the production of 7β-OHSt is still a challenge due to the lack of cheap 7β-hydroxy precursor and the difficulty in regio- and stereo-selectively hydroxylation at the inert C7 site of steroids in industry. The conversion of phytosterols by Mycolicibacterium species to the commercial precursor, androst-4-ene-3,17-dione (AD), is one of the basic ways to produce different steroids. This study presents a way to produce a basic 7β-hydroxy precursor, 7β-hydroxyandrost-4-ene-3,17-dione (7β-OH-AD) in Mycolicibacterium, for 7β-OHSt synthesis. A mutant of P450-BM3, mP450-BM3, was mutated and engineered into an AD producing strain for the efficient production of 7β-OH-AD. The enzyme activity of mP450-BM3 was then increased by 1.38 times through protein engineering and the yield of 7β-OH-AD was increased from 34.24 mg L- 1 to 66.25 mg L- 1. To further enhance the performance of 7β-OH-AD producing strain, the regeneration of nicotinamide adenine dinucleotide phosphate (NADPH) for the activity of mP450-BM3-0 was optimized by introducing an NAD kinase (NADK) and a glucose-6-phosphate dehydrogenase (G6PDH). Finally, the engineered strain could produce 164.52 mg L- 1 7β-OH-AD in the cofactor recycling and regeneration system. This was the first report on the one-pot biosynthesis of 7β-OH-AD from the conversion of cheap phytosterols by an engineered microorganism, and the yield was significantly increased through the mutation of mP450-BM3 combined with overexpression of NADK and G6PDH. The present strategy may be developed as a basic industrial pathway for the commercial production of high value products from cheap raw materials.


The E3 ubiquitin ligase DESYNAPSIS1 regulates synapsis and recombination in rice meiosis.
Synaptonemal complex (SC) assembly and homologous recombination, the most critical events during prophase I, are the prerequisite for faithful meiotic chromosome segregation. However, the underlying regulatory mechanism remains largely unknown. Here, we reveal that a functional RING finger E3 ubiquitin ligase, DESYNAPSIS1 (DSNP1), plays significant roles in SC assembly and homologous recombination during rice meiosis. In the dsnp1 mutant, homologous synapsis is discontinuous and aberrant SC-like polycomplexes occur independent of coaligned homologous chromosomes. Accompanying the decreased foci of HEI10, ZIP4, and MER3 on meiotic chromosomes, the number of crossovers (COs) decreases dramatically in dsnp1 meiocytes. Furthermore, the absence of central elements largely restores the localization of non-ZEP1 ZMM proteins and the number of COs in the dsnp1 background. Collectively, DSNP1 stabilizes the canonical tripartite SC structure along paired homologous chromosomes and further promotes the formation of COs.


Synchronism of pressor response and grooming behavior in freely moving, conscious rats following intracerebroventricular administration of ACTH/MSH-like peptides.
After the i.c.v. administration of 300 pmol ACTH-(1-24) or [Nle4,D-Phe7]alpha-MSH, a long-lasting increase in blood pressure was observed synchronously with the incidence of excessive grooming. Two structurally related peptides with no grooming behavior-inducing potency, ACTH-(7-16)-NH2 and gamma 2-MSH, in doses of 300 and 500 pmol, respectively, caused a slight and short-lasting increase in blood pressure or had no effect, respectively. When the grooming behavior-inducing effect of ACTH-(1-24) was abolished, either by the prior manipulation of central dopaminergic neurotransmission by the i.c.v. administration of the dopamine receptor antagonist, haloperidol, or, due to the occurrence of single-dose tolerance to ACTH-(1-24), the pressor response was abolished as well. These data are in support of the postulate that the incidence of grooming behavior and the elevation of blood pressure are temporally associated and indicate that the two phenomena are causally related.


A multi-platform sensor for selective and sensitive H2S monitoring: Three-dimensional macroporous ZnO encapsulated by MOFs with small Pt nanoparticles.
The high-selectivity and high-sensitivity determination of trace concentrations of toxic gases is a major challenge when using semiconductor metal oxide (SMO) gas sensors in complicated real-world environments. In this study, by strategically combining a three-dimensional inverse opal (3DIO) macroporous ZnO substrate and a ZIF-8 outer filter membrane, two series of sensors with Pt NPs loaded at different locations are developed. In the optimal 3DIO ZnO@ZIF-8/Pt sensor, the existence of small Pt NPs in ZIF-8 cavities can effectively accelerate the absorption of H2S, capture electrons from the N site of ZIF-8, and donate the electron to the S site of H2S, as indicated by density functional theory simulations, leading to a significantly increased response to H2S. Together with the molecular-sieving effect that ZIF-8 exerts on gas molecules with larger kinetic diameters, the 3DIO ZnO@ZIF-8/Pt sensor exhibits a high response to H2S (118-5.5 ppm), a detection limit of 40 ppb, and importantly, a 59-fold higher selectivity to H2S against typical interference gases. In addition, the 3DIO ZnO@ZIF-8/Pt sensor is developed as a multi-platform sensor to evaluate trace concentrations of H2S in meat quality assessment, halitosis diagnosis, and automobile exhaust assessment.


MicroED: conception, practice and future opportunities.
This article documents a keynote seminar presented at the IUCr Congress in Prague, 2021. The cryo-EM method microcrystal electron diffraction is described and put in the context of macromolecular electron crystallography from its origins in 2D crystals of membrane proteins to today's application to 3D crystals a millionth the size of that needed for X-ray crystallography. Milestones in method development and applications are described with an outlook to the future.


Epilepsy surgery for children and adolescents: evidence-based but underused.
Paediatric epilepsy surgery is an increasingly used evidence-based management option with low risks for complications. Developments in neuroimaging techniques and other advanced diagnostics have widened the spectrum of children who could benefit from the procedure, and surgery is now considered a standard management approach for epilepsy. Available data indicate that early surgery improves outcomes. Despite these considerable advances, epilepsy surgery in children is still underused. In this Review, we summarise the indications, patient selection, principles of presurgical investigations, optimal timing, and types of epilepsy surgery. We also examine comprehensive outcomes after surgery, including seizure outcomes, complications, cognition, neurodevelopment, vocational outcome, and health-related quality of life of children and their parents. Successful epilepsy surgery could lead to improvement in all these areas. Children should, therefore, be referred early for evaluation in an appropriately competent centre.


Biodegradable polymer membrane used as septal splint.
The treatment of a crooked nose is one of the most challenging rhinoplastic procedures. Correction of the abnormally curved or fractured septum has been reported using mostly scoring techniques, septoplasty and submucous resection techniques; cartilaginous spreader grafts can also be sutured to the distorted septum. Extracorporal septal straightening and repositioning/refixation is another useful but difficult technique. A common problem of septal cartilaginous grafting techniques is to harvest enough straight cartilage to correct the deformity. (Other donor sites such as rib cartilage are used, but harvesting additional cartilage is a time-consuming procedure and carries the risk of donor site morbidity.) Recent studies have been published using alloplastic internal splinting of the deformed septum. The use of poly p-dioxanone foils and porous polyethylene has been suggested before. In this study, a novel grafting material, a PolyMax membrane that has potential advantages over both materials, is presented. This is a porous biodegradable polymer made out of 70:30 poly(L-lactide-co-D,L-lactide) that remains stable for at least 7 months. Poly p-dioxanone loses its stability after only 2 months, whereas porous polyethylene is a permeable material that is controversial due to possible complications in cases of membrane exposure and infection. In this preliminary report the PolyMax membrane was used successfully in 3 patients.


Characteristics of a population-wide sample of smokers recruited proactively for the ESCAPE trial.
To describe the characteristics of a sample of smokers recruited proactively into a smoking cessation trial, and to compare these characteristics with the wider population using data from the General Household Survey (GHS) and National Statistics Omnibus Survey. Sample recruited for a randomized controlled trial. Between August 2007 and October 2008, 123 general practices mailed questionnaires to smokers in the U.K. identified from computer records. Smokers willing to participate in a trial of personalized computer-tailored feedback returned the questionnaires to the research team. The characteristics of the sample were compared with the wider population using data from the GHS and National Statistics Omnibus Survey, and Index of Material Deprivation scores. A response rate of 11.4% (n = 6697) was achieved. The sample was demographically similar to the population sample, with an even distribution of participants from areas of both high and low deprivation. The sample was more dependent than the GHS sample, but less dependent than clinic samples. Distribution by motivation and readiness to quit was similar to population estimates. Public health strategies targeting the entire population of smokers are needed to counter the low recruitment rates resulting from the traditional reactive methods of recruitment to smoking cessation studies. Using computerized records to identify and contact patients who are smokers is a simple method of recruiting a larger, more representative sample of smokers.


Evaluating and comparing the clinical characteristics between adult-onset and childhood-onset atopic dermatitis in an Asian clinical cohort.
Atopic dermatitis (AD) is one of the most prevalent chronic inflammatory skin conditions. We aimed to describe the clinical features of adult-onset and childhood-onset AD in a multi-ethnic Asian population. A retrospective study was performed of 188 patients with AD managed at a tertiary skin institution in Singapore. Patient demographics, clinical features and disease scores were analysed. Clinical features related to pigmentary changes, such as orbital darkening and Dennie-Morgan folds were more prevalent among childhood-onset AD patients than in adult-onset AD patients. Similarly, features related to prolonged scratching or friction, such as anterior neck folds, perifollicular accentuation and infra-auricular/infranasal fissuring were also more prevalent in childhood-onset AD patients. Disease scores such as SCORAD and EASI were not different between patients with childhood versus adult-onset disease. There were significant differences in clinical features between childhood-onset and adult-onset AD. Certain features are related to pigmentary changes and might be more accentuated in patients with skin of colour. Further studies are needed to understand how the different features might be clinically significant and related to the various AD endotypes and disease trajectories.


Synthesis and pharmacological activities of 13-dehydro derivatives of primary prostaglandins.
13-Dehydro derivatives of prostaglandin E1, E2, E3, F1 alpha and F2 alpha were synthesized. Compared with natural prostaglandins, 13-dehydro analogues were found to exhibit more potent inhibitory activity against human platelet aggregation and relaxation of guinea-pig isolated trachea, while they showed less potent activity of contraction of guinea-pig isolated ileum.


Complete Genome Sequence of O'nyong Nyong Virus Isolated from a Febrile Patient in 2017 in Uganda.
Despite causing numerous large outbreaks in the 20th century, few isolates of o'nyong nyong virus (ONNV) have been fully sequenced. Here, we report the complete genome sequence of an isolate of ONNV obtained from a febrile patient in northwest Uganda in 2017, designated ONNV UVRI0804.


The value of EYA1/3/4 in clear cell renal cell carcinoma: a study from multiple databases.
There is evidence from multiple studies that dysregulation of the Eyes Absent (EYA) protein plays multiple roles in many cancers. Despite this, little is known about the prognostic significance of the EYAs family in clear cell renal cell carcinoma (ccRCC). We systematically analyzed the value of EYAs in Clear Cell Renal Cell Carcinoma. Our analysis included examining transcriptional levels, mutations, methylated modifications, co-expression, protein-protein interactions (PPIs), immune infiltration, single-cell sequencing, drug sensitivity, and prognostic values. We based our analysis on data from several databases, including the Cancer Genome Atlas database (TCGA), the Gene Expression Omnibus database (GEO), UALCAN, TIMER, Gene Expression Profiling Interactive Analysis (GEPIA), STRING, cBioPortal and GSCALite. In patients with ccRCC, the EYA1 gene was significantly highly expressed, while the expression of EYA2/3/4 genes showed the opposite trend. The level of expression of the EYA1/3/4 gene was significantly correlated with the prognosis and clinicopathological parameters of ccRCC patients. Univariate and multifactorial Cox regression analyses revealed EYA1/3 as an independent prognostic factor for ccRCC, establishing nomogram line plots with good predictive power. Meanwhile, the number of mutations in EYAs was also significantly correlated with poor overall survival (OS) and progression-free survival (PFS) of patients with ccRCC. Mechanistically, EYAs genes play an essential role in a wide range of biological processes such as DNA metabolism and double-strand break repair in ccRCC. The majority of EYAs members were related to the infiltration of immune cells, drug sensitivity, and methylation levels. Furthermore, our experiment confirmed that EYA1 gene expression was upregulated, and EYA2/3/4 showed low expression in ccRCC. The increased expression of EYA1 might play an important role in ccRCC oncogenesis, and the decreased expression of EYA3/4 could function as a tumor suppressor, suggesting EYA1/3/4 might serve as valuable prognostic markers and potential new therapeutic targets for ccRCC.


Implementation of a Breast Intraoperative Oncoplastic Form to Aid Management of Oncoplastic Surgery.
Oncoplastic breast conservation surgery (BCS) uses concurrent reduction and/or mastopexy with lumpectomy to improve aesthetic outcomes. However, tissue rearrangement can shift the original tumor location site in relation to external breast landmarks, resulting in difficulties during re-excision for a positive margin and accurate radiation targeting. We developed the Breast Intraoperative Oncoplastic (BIO) form to help depict the location of the tumor and breast reduction specimen. This study seeks to assess physician perspectives of the implementation outcomes. From February 2021 to April 2021, the BIO form was used in 11 oncoplastic BCS cases at a single institution. With institutional review board approval, surgical oncologists (SOs), plastic surgeons (PSs), and radiation oncologists (ROs) were administered a 12-question validated survey on Acceptability of Intervention Measure (AIM), Intervention Appropriateness Measure (IAM), and Feasibility of Intervention Measure (FIM), using a 5-point Likert scale during initial implementation and at 6-month reassessment. Twelve physicians completed the survey initially (4 SOs, 4 PSs, and 4 ROs). The mean scores for Acceptability of Intervention Measure, Intervention Appropriateness Measure, and Feasibility of Intervention Measure were high (4.44, 4.56, and 4.56, respectively). Twelve completed the second survey (5 SOs, 3 PSs, and 4 ROs). The mean scores were marginally lower (4.06, 4.21, and 4.25). There were no significant differences when stratified by number of years in practice or specialty. Free text comments showed that 75% of physicians found the form helpful in oncoplastic BCS. The data indicate high feasibility, acceptability, and appropriateness of the BIO form. Results of this study suggest multidisciplinary benefits of implementing the BIO form in oncoplastic BCS.


An ECM-Mimicking, Injectable, Viscoelastic Hydrogel for Treatment of Brain Lesions.
Brain lesions can arise from traumatic brain injury, infection, and craniotomy. Although injectable hydrogels show promise for promoting healing of lesions and health of surrounding tissue, enabling cellular ingrowth and restoring neural tissue continue to be challenging. It is hypothesized that these challenges arise in part from the mismatch of composition, stiffness, and viscoelasticity between the hydrogel and the brain parenchyma, and this hypothesis is tested by developing and evaluating a self-healing hydrogel that not only mimics the composition, but also the stiffness and viscoelasticity of native brain parenchyma. The hydrogel is crosslinked by dynamic boronate ester bonds between phenylboronic acid grafted hyaluronic acid (HA-PBA) and dopamine grafted gelatin (Gel-Dopa). This HA-PBA/Gel-Dopa hydrogel could be injected into a lesion cavity in a shear-thinning manner with rapid hemostasis, high tissue adhesion, and efficient self-healing. In an in vivo mouse model of brain lesions, the multi-functional injectable hydrogel is found to support neural cell infiltration, decrease astrogliosis and glial scars, and close the lesions. The results suggest a role for extracellular matrix-mimicking viscoelasticity in brain lesion healing, and motivate additional experimentation in larger animals as the technology progresses toward potential application in humans.


[Sigmoid colon diverticulitis : Treatment modalities 2011-2013].
Diverticulosis is a relevant disease in Germany with a prevalence of over 60 % in patients aged ≥70 years. The S2k guidelines for the treatment of diverticulosis were recently published. Systematic epidemiological data on treatment modalities do not exist. Analysis of in-hospital treatment modalities for diverticulosis based on data from the Federal Office of Statistics. Approximately 130,000 inpatient cases of diverticulosis are treated in Germany per year. Approximately 25 % undergo surgery and of these slightly under 50 % (12,000 procedures) are carried out by laparoscopy. The complication rates are 18 % in a best case scenario and up to 85 % in a worst case scenario. A stage-adjusted classification of treatment modalities based on data from the Federal Office of Statistics is currently practically impossible. To enable stage-adjusted epidemiological analysis of diverticulosis, a standardized and transparent documentation system enabling systematic analysis is necessary, which does not currently exist (e. g. ICD 10 coding); moreover, information on conservative and interventional treatment options are not included in the operations and procedures key (OPS) coding system.


Detecting multiple autoantibodies to diagnose autoimmune co-morbidity (multiple autoimmune syndromes and overlap syndromes): a challenge for the autoimmunologist.
In the last 15 years, the estimated prevalence of autoimmune diseases increased from about 4 to 9.4%. Autoimmune co-morbidity (i.e., the association between two or more autoimmune diseases in the same patient) is present in 0.4-0.5% of the worldwide population, more frequently in patients with multiple sclerosis, rheumatoid arthritis, autoimmune thyroid disease, type 1 diabetes, inflammatory bowel disease and vitiligo. The most common associations between autoimmune diseases define two clusters: the multiple autoimmune syndromes and overlap syndromes. This review highlights the importance of multiple antibody assays in the diagnosis of multiple autoimmune and overlap syndromes and summarizes the general conditions of autoantibody detection using the model of the five W's: why, who, what, when and where. These conditions represent a new challenge for clinical and laboratory autoimmunologists, who, in a multidisciplinary arena, cooperate in investigating and treating multiple autoimmune disorders.


Effect of N-ethylmaleimide, chymotrypsin, and H₂O₂ on the viscoelasticity of human erythrocytes: experimental measurement and theoretical analysis.
The physiological functions of erythrocytes depend critically on their morphology, deformability, and aggregation capability in response to external physical and chemical stimuli. The dynamic deformability can be described in terms of their viscoelasticity. We applied jumping optical tweezers to trap and stretch individual red blood cells (RBCs) to characterize its viscoelasticity in terms of the Young's modulus and viscosity by analyzing the experimental data of dynamic deformation using a 2-parameter Kelvin solid model. The effects of three chemical agents (N -ethylmaleimide, Chymotrypsin, and Hydrogen peroxide) on RBC's mechanical properties were studied by comparing the Young's modulus and viscosity of RBCs with and without these chemical treatments. Although the effects of each of these chemicals on the molecular structures of RBC may not be exclusive, based on the dominant effect of each chemical, we attempted to dissect the main contributions of different constituents of the RBC membrane to its viscosity and elasticity.


Demonstration that glycoprotein G is the attachment protein of respiratory syncytial virus.
Two monospecific rabbit antisera to the G glycoprotein, one induced with purified G and the second with a recombinant vaccinia virus containing the gene for G, inhibit the attachment of purified [35S]methionine-labelled Long strain of respiratory syncytial virus to monolayers of HeLa cells. Attachment was not inhibited by monospecific rabbit antisera to glycoprotein F induced with either purified F or with a recombinant vaccinia virus containing the gene for F.


Flexion strength of the toes in the normal foot. An evaluation using magnetic resonance imaging.
Flexion of the toes may be active from muscle contraction or passive from the reversed windlass function of the plantar aponeurosis. The aim of this study was to estimate the flexion moments the muscles of the foot and long digital flexors may be capable of generating and compare these calculations with published data. Magnetic resonance images were used to measure the maximal cross-sectional area of the foot muscles and long digital flexors, along with the radius of curvature of the metatarsal heads. Using known physiological data the maximal flexion moments the muscles may be able to generate at the metatarsophalangeal (MTP) joints were calculated. The methodology overestimates muscle strength and flexion moments at the metatarsophalangeal joints. The calculated maximal flexion moment at the 1st MTP joint is 4.27-6.84 Nm, for the 2nd, 3rd and 4th MTP joints 3.06-4.91 Nm, and the 5th MTP joint 0.47-0.75 Nm. The flexion moments the muscles may generate at the MTP joints do not account for the flexion forces seen in normal walking. Given that maximal strength is not used in normal walking, we conclude that the reversed windlass mechanism of the plantar aponeurosis must be important in normal function of the toes.


Delayed hypersensitivity. I. Effect of in vitro exposure of cells to antigen upon leukocytic transfer of delayed hypersensitivity.
Exposure to picryl guinea pig albumin with 3-6 picryl groups per mole failed to affect the ability of peritoneal exudate or peripheral blood leukocytes from sensitized donors to transfer delayed sensitivity to normal recipients. In contrast, conjugates containing 40-48 picryl groups per mole altered the ability of exposed leukocytes to transfer delayed sensitivity. Evidence is presented that highly conjugated guinea pig albumin is self-aggregating. Lightly conjugated albumin, previously heat-aggregated, also was effective in "desensitization." The properties of antigen size, cell association of antigen after exposure, and desensitization appear to be associated.


Value of multi-channel somatosensory evoked potentials recording in patients undergoing scoliosis correction surgery.
We aimed to investigate the value of intraoperative multi-channel recording of somatosensory evoked potentials (SSEPs) in patients undergoing posterior instrumentation surgery with fusion. This study included 176 patients with scoliosis who underwent posterior correction surgery from January 2019 to June 2020. Among them, 88 patients underwent routine SSEPs monitoring via single-channel (Cz'-Fpz) cortical recording (control group), while the remaining 88 patients underwent multi-channel (Cz'-Fpz and C3'-C4') SSEPs monitoring in the cortex. Chi-square and Fisher's exact tests were used to analyze the influence of age, spinal deformity classification, and Cobb angle on waveform differentiation and the success rate of SSEPs monitoring. Univariate analysis revealed that age, type of scoliosis, and Cobb angle exerted significant effects on the success rate of intraoperative SSEPs monitoring, and the SSEPs waveform differentiation rate was poorest among patients with congenital scoliosis. Intraoperative monitoring results indicated that the success rate of single-channel SSEPs monitoring was 90.9%, while that of multi-channel monitoring was 98.9% (P < 0.05). Among the intraoperative alarm cases, the incidence of adverse events after single-channel SSEPs monitoring was 66.7%, while the incidence of adverse events after multi-channel SSEPs monitoring was only 28.6%. Multi-channel cortical SSEPs monitoring can effectively and accurately evaluate the function of the posterior column of the spinal cord. Use of multi-channel SSEP monitoring may help to improve the success rate of monitoring and reduce the incidence of postoperative adverse events in patients with congenital scoliosis.


Glutamate-induced calcium loads: effects on energy metabolism and neuronal viability.
1. Glutamate-induced increases in intracellular free Ca2+ concentration ([Ca2+]i) were recorded from cultured rat hippocampal neurons with single cell microfluorometry. The [Ca2+]i increase did not correlate with glutamate-induced cell death, consistent with the idea that Ca2+ accumulates in an intracellular store, and that loading this store might be toxic. 2. Glutamate-induced Ca2+ loads were buffered by a low-affinity, high-capacity process that was inhibited by the mitochondrial uncoupling agent FCCP and modulated by intracellular Na+. 3. Glutamate-induced Ca2+ loads also produced an intracellular acidification. The acidification was prevented by the metabolic inhibitor 2-deoxyglucose, mimicked by Ba2+, and inhibited by microinjection of ruthenium red. 4. These data are consistent with the hypothesis that mitochondria sequester glutamate-induced Ca2+ loads producing a metabolic acidosis; metabolic stress may contribute to glutamate-induced neuronal death.


Peroxiredoxin-4 and Dopamine D5 Receptor Interact to Reduce Oxidative Stress and Inflammation in the Kidney.
Aims: Reactive oxygen species are highly reactive molecules generated in different subcellular compartments. Both the dopamine D5 receptor (D5R) and endoplasmic reticulum (ER)-resident peroxiredoxin-4 (PRDX4) play protective roles against oxidative stress. This study is aimed at investigating the interaction between PRDX4 and D5R in regulating oxidative stress in the kidney. Results: Fenoldopam (FEN), a D1R and D5R agonist, increased PRDX4 protein expression, mainly in non-lipid rafts, in D5R-HEK 293 cells. FEN increased the co-immunoprecipitation of D5R and PRDX4 and their colocalization, particularly in the ER. The efficiency of Förster resonance energy transfer was increased with FEN treatment measured with fluorescence lifetime imaging microscopy. Silencing of PRDX4 increased hydrogen peroxide production, impaired the inhibitory effect of FEN on hydrogen peroxide production, and increased the production of interleukin-1β, tumor necrosis factor (TNF), and caspase-12 in renal cells. Furthermore, in Drd5-/- mice, which are in a state of oxidative stress, renal cortical PRDX4 was decreased whereas interleukin-1β, TNF, and caspase-12 were increased, relative to their normotensive wild-type Drd5+/+ littermates. Innovation: Our findings demonstrate a novel relationship between D5R and PRDX4 and the consequent effects of this relationship in attenuating hydrogen peroxide production in the ER and the production of proinflammatory cytokines. This study provides the potential for the development of biomarkers and new therapeutics for renal inflammatory disorders, including hypertension. Conclusion: PRDX4 interacts with D5R to decrease oxidative stress and inflammation in renal cells that may have the potential for translational significance. Antioxid. Redox Signal. 38, 1150-1166.


Infantile disease with microvesicular fatty infiltration of viscera spontaneously occurring in the C3H-H-2(0) strain of mouse with similarities to Reye's syndrome.
The clinical, biochemical and histopathological findings of an infantile disease occurring in the C3H-H-2 degree strain of mice, which has similarities with Reye's syndrome in children, is described.


In vivo experimental testing and model identification of human scalp skin.
A comprehensive experimental/numerical procedure is formulated and validated for the in vivo characterization of the mechanical properties of human skin and the simulation of reconstructive surgery. The procedure uses in vivo experimental tests on undermined skin flaps, which can be performed during surgery, a numerical model formulated within the framework of nonlinear finite strain elasticity and a nonlinear parameter identification technique for the calibration of the model from indirect measurements. The procedure is applied to characterize the scalp skin tested in Raposio and Nordström (Skin Res. Technol. 4 (1998) 94). The skin is treated as a time independent, isotropic and hyperelastic membrane and the problem is solved through a finite element discretization. The study highlights that the model parameters can be determined with good accuracy using displacement measurements of a few points in the domain.


Binding of monoiodinated neuropeptide Y to hippocampal membranes and human neuroblastoma cell lines.
Monoiodinated radioligands of the homologous 36-amino acid peptides, neuropeptide Y (NPY) and peptide YY, were prepared by reverse phase high performance liquid chromatography with isocratic elution. [125I-Tyr1]- and [125I-Tyr36]monoiodoNPY bound equally well to a single class of high affinity binding sites on synaptosomal membranes prepared from porcine hippocampus (Kd = 1.0 X 10(-10) M) whereas iodine substitution in Tyr27, for example, partly interfered with the receptor binding. The receptors on the hippocampal membranes did not distinguish between neuropeptide Y and peptide YY either in their monoiodinated or in their unlabeled forms. Six out of twelve human neuroblastoma cell lines had high affinity binding sites for monoiodinated NPY ranging from 2 to 145 X 10(3) sites per cell. The NPY binding to three of the cell lines, SMS-MSN, SMS-KAN, and CHP-234 was of relatively high affinity (Kd = 1.3 to 6.1 X 10(-10) M), and, as in the hippocampal membranes, the long C-terminal fragment, NPY(13-36)peptide was also a relatively potent ligand for these receptors. Two other neuroblastoma cell lines, MC-IXC and CHP-212, expressed NPY receptors characterized by a lower affinity (Kd = 4.8 and 24.6 X 10(-9) M) and negligible cross-reactivity with the C-terminal fragment. It is concluded that monoiodinated radioligands of the tyrosine-rich neuropeptide Y can be prepared and that receptors for these ligands in two apparently different subtypes are found on a series of human neuroblastoma cell lines.


Chitosan Schiff bases-based polyelectrolyte complexes with graphene quantum dots and their prospective biomedical applications.
Chitosan (Cs) bis-aldehyde Schiff base derivatives were synthesized by condensation of Cs with three bis-aldehydes namely; butane-1,4-diyl bis(4-formylbenzoate), N,N'-(butane-1,4-diyl)bis(2-(4-formylphenoxy)acetamide) and 4,4'-(butane-1,4-diylbis(oxy))dibenzaldehyde. The prepared Cs derivatives were blended with carboxymethyl chitosan(CMC) and graphene quantum dots (GQDs) to produce semi-IPNs polyelectrolyte complexes (PECs). and characterized with respect to their molecular structure and physio-chemical properties. The antibacterial activity against H. pylori (and in vitro Inosine 5'-monophosphate dehydrogenase IMPDH inhibitory assay) was evaluated. Additionally, a preliminary in vitro assessment for wound healing was performed against PECs in which wound closure percentages, and rates were investigated indicating an accelerated wound healing compared with untreated cells. The PEC based on Schiff base PEC containing amide linkage showed the highest wound healing ability. A minimal inhibitory concentration (MIC) was obtained for the PEC sample containing Cs Schiff base derived from 4,4'-(butane-1, 4-diylbis(oxy))dibenzaldehyde at a dose of 0.98 μg/ml inhibiting H. pylori growth by 100%. Additionally, the selected above-mentioned compound was selected to test its inhibitory activity against the HpIMPDH enzyme in addition to its selectivity towards the hIMPDH2 enzyme and was found to have promising activity against the HpIMPDH enzyme with IC50 value of 0.65 μM, and to be safer and less active against the hIMPDH2 enzyme with IC50 > 10 μM, reflecting its selectivity.


Design, synthesis and bio-evaluation of novel 2-aryl-4-(3,4,5-trimethoxy-benzoyl)-5-substituted-1,2,3-triazoles as the tubulin polymerization inhibitors.
A series of 2-aryl-4-(3,4,5-trimethoxybenzoyl)-5-substituted-1,2,3-triazoles were designed, synthesized and evaluated for the anticancer activities. Based on the model of DMAM-colchicine-tubulin complex interactions, various saturated nitrogen-containing heterocycles were introduced to the C5-position of 1,2,3-triazol to interact with a tolerant region at the entrance of the binding-pocket and increase the aqueous solubility of the compounds. All designed compounds were concisely synthesized by one-pot oxidative cyclization. Most compounds exhibited moderate antiproliferative activity with IC50 values in the micromolar to sub-micromolar range. Among them, 5g posed N-acyl-piperazine moiety at the C5-position of B-ring showed most potent against cancer cells, with IC50 values of 0.084-0.221 μM 5g potently disrupted microtubule/tubulin dynamics, induced cell cycle arrest at G2/M phase in SGC-7901 cells. In addition, molecular modeling studies suggested that 5g probably binds to the colchicine site of tubulin.


Determinant factors of spectrum of missense variants in mucopolysaccharidosis IVA gene.
Design of efficient treatment strategies for diseases requires clarification of the nature of each mutation causing the disease. In this study, we have investigated three factors to correctly predict the correlation between genotype and phenotype on N-acetylgalactosamine-6-sulfate sulfatase (GALNS) gene responsible for one of lysosomal storage diseases, known as mucopolysaccharidosis IVA (MPS IVA); (i) evolutionary conservation of amino acid residues among family proteins, (ii) conservativeness of amino acid changes in GALNS, and (iii) structural conservation of amino acid residue. The results showed that (i) the likelihood of a missense variant causing MPS IVA was directly correlated with the level of evolutionary conservation and inversely correlated with conservativeness but not correlated with the structural conservation, (ii) the disease-causative mutations were 9 times more likely to be located on the 'highly conserved' residues than the polymorphisms, (iii) the likelihood of 'non-conservative' amino acid changes in missense mutations was 6.8 times higher than those in the polymorphisms, (iv) the degree of evolutionary conservation was nearly as predictive in phenotype as that of conservativeness of amino acid changes, and (v) the combination of the two factors, evolutionary conservation and conservativeness, provides a better association between missense variants and clinical severity with higher sensitivity (83.5-88.9%) and specificity (71.4-88.3%), than that obtained by either factor alone. These findings suggest that the combination of evolutionary conservation and conservativeness is a useful tool to predict the effect of each mutation on the clinical phenotype and can be applied to the analysis of phenotype/genotype relation in other genetic diseases.


Three-dimensional echocardiographic reconstruction: qualitative and quantitative evaluation of ventricular function.
Three-dimensional (3-D) images of the human left ventricle were reconstructed from 2-dimensional echocardiographic pictures. All images were recorded at held end-expiration from an optimal point where a high-quality parasternal long-axis view maximally visualizing the left ventricle could be obtained. Multiple short-axis views were obtained from the same reference point. Interactive computer techniques were used to reconstruct 3-D shells of endocardium and epicardium. End-diastolic and end-systolic outlines were superimposed after correcting for motion during the cardiac cycle to demonstrate wall motion. Images were displayed from different perspectives and regional wall thickness, thickening, and motion were then demonstrated using surface map displays. Volumes and derived indices of left ventricular function were calculated. The ejection fraction of normal patients was 69 +/- 9%, compared to 57 +/- 7% in infarct patients; the latter results correlated well with contrast angiography. 3-D echocardiographic reconstruction provides the observer with a spatial appreciation of left ventricular wall motion and thickness, as well as useful quantitative information. The system requires only a standard echocardiographic recorder and simple computer hardware.


Fetal H-2 odortypes are evident in the urine of pregnant female mice.
The major histocompatibility complex (MHC) imparts to each mouse an individual urinary odor, called "odortype", which reflects its MHC genotype. Perception of odortypes affects mate selection and embryonic implantation. Recent findings that odortypes are expressed as early as one day of age suggested that they might already be expressed in utero. We now report that at 9-12 days of gestation, odortypes specified by paternal (non-maternal) MHC haplotypes become apparent in maternal urine. Thus, odortypes are expressed in utero, can be sensed even before birth, and may serve in familial identification and communication.


Increased diaphragm echodensity correlates with postoperative pulmonary complications in patients after major abdominal surgery: a prospective observational study.
Associated with increased morbidity and mortality, postoperative pulmonary complications (PPCs) often occur after major abdominal surgery. Diaphragmatic dysfunction is suggested to play an important role in the development of PPCs and diaphragm echodensity can be used as an indicator of diaphragm function. This study aimed to determine whether diaphragm echodensity could predict the occurrence of PPCs in patients after major abdominal surgery. Diaphragm ultrasound images of patients after major abdominal surgery were collected during spontaneous breathing trials. Echodensity was quantified based on the right-skewed distribution of grayscale values (50th percentile, ED50; 85th percentile, ED85; mean, EDmean). Intra- and inter-analyzer measurement reproducibility was determined. Outcomes including occurrence of PPCs, reintubation rate, duration of ventilation, and length of ICU stay were recorded. Diaphragm echodensity was measured serially in 117 patients. Patients who developed PPCs exhibited a higher ED50 (35.00 vs. 26.00, p < 0.001), higher ED85 (64.00 vs. 55.00, p < 0.001) and higher EDmean (39.32 vs. 33.98, p < 0.001). In ROC curve analysis, the area under the curve of ED50 for predicting PPCs was 0.611. The optimal ED50 cutoff value for predicting the occurrence of PPCs was 36. According to this optimal ED50 cutoff value, patients were further divided into a high-risk group (ED50 > 36, n = 35) and low-risk group (ED50 ≤ 36, n = 82). Compared with the low-risk group, the high-risk group had a higher incidence of PPCs (unadjusted p = 0.003; multivariate-adjusted p < 0.001). Diaphragm echodensity can be feasibly and reproducibly measured in mechanically ventilated patients. The increase in diaphragm echodensity during spontaneous breathing trials was related to an increased risk of PPCs in patients after major abdominal surgery.


Safety and Effectiveness of Rasburicase in the Control of Hyperuricemia in Pediatric Patients with Non-Hodgkin's Lymphoma and Acute Leukemia: An Open-Label, Single-Arm, Multi-center, Interventional Study.
Despite rasburicase's proven efficiency in Caucasians, Japanese, and Koreans, studies evaluating the safety and effectiveness of rasburicase in Chinese pediatric patients with non-Hodgkin's lymphoma (NHL) and acute leukemia (AL) in particular are lacking. The aim was to evaluate the safety and effectiveness of rasburicase in Chinese pediatric patients with NHL and AL. In this phase IV, open-label, non-randomized, single-arm, multi-center, interventional study (NCT04349306), children newly diagnosed with NHL or AL who received 0.20 mg/kg/day of rasburicase were included. The primary objective was to assess the safety of rasburicase by the incidence of adverse events (AEs). The secondary objective was to determine the effectiveness of rasburicase in the control of hyperuricemia. Out of 50 patients, 25 reported a total of 76 treatment-emergent adverse events (TEAEs), including eight TEAEs of grade ≥ 3 in 12 patients. A drug-related serious AE was reported in one patient, and there was no incidence of death. The response rate in the intent-to-treat population was 100.0% (95% confidence interval 82.4-100.0) in patients (n = 19) with baseline uric acid level of > 8.0 mg/dL. Similarly, the response rate was 86.2% (n = 25) among 29 patients (60.4%) with baseline uric acid levels of ≤ 8.0 mg/dL. The maximum mean percentage decrease of plasma uric acid level in the overall patients was 96.9%. Rasburicase was well tolerated and effective in controlling hyperuricemia in Chinese pediatric patients with NHL and AL.


Dietary inflammatory index and breast cancer risk: an updated meta-analysis of observational studies.
This updated meta-analysis sought to determine whether the pro-inflammatory potential of diet is a risk factor for breast cancer (BrCa) development, for the first time focusing on the effects of design heterogeneity. The search was performed using Scopus, PubMed, and Embase databases. Data were extracted from twenty-one eligible studies, including eleven cohorts (336,085 participants/20,033 incidence cases), and ten case-control studies (9,833 cases/12,752controls). The random-effect was used to calculate the relative risk (RR) using STATA 16 software. The highest dietary inflammatory index (DII) vs. the lowest category showed 16% increased risk of BrCa (95% CI: 1.06-1.26; I2 = 62.8%, P (I2) < 0.001). This was notable in post-menopausal status (RR = 1.13, 95% CI: 1.04-1.22), women with body mass index (BMI) ≥ 30 kg/m2 (RR = 1.35, 95% CI: 1.07-1.63), and study populations from developing countries (RR = 1.79, 95% CI: 1.12-2.47). Methodological covariates were subject to subgroup meta-analyses and showed stronger results among case-control studies (RR = 1.50, 95% CI: 1.20-1.80), studies considered age-matched controls (RR = 1.56, 95% CI: 1.19-1.93) and hospital-based controls (RR = 2.11, 95% CI: 1.58-2.64), and cohort studies identified by prolong follow-up durations (RR = 1.13, 95% CI: 1.03-1.22). This updated meta-analysis highlighted the pro-inflammatory diet as a risk factor for BrCa, especially among women in post-menopausal status, obese groups, and developing countries. Meta-analysis in methodological subgroups could improve results, less affected by heterogeneity, and suggested subclassification with important implications for future epidemiological designs and even clinical management.


New insight into the changes in metal-phosphonate complexes from the addition of CaCO3 to enhance ferric flocculation for efficient phosphonate removal.
Due to the stable chelating effect of organic phosphonates in wastewater, phosphonates with increasing emission are difficult to be removed effectively by traditional ferric salt flocculation, which has posed tough challenges for reducing total phosphorus pollution in recent years. In this work, calcium carbonate (CaCO3) was introduced to work together with the widely investigated flocculant of ferric chloride (FeCl3) to realize an efficient removal of nitrilotrismethylenephosphonic acid (NTMP) at much lower dosage of FeCl3. With an aid of synergy effect from together use of CaCO3 and FeCl3, the remaining concentration as low as 0.16 mg-P/L, far below the sewage discharge limit (0.5 mg-P/L), was simply obtained with a significantly reduced Fe/P molar ratio at only 4, resulting from calcium source donor to form more stable Fe-Ca-P tridentate bridging complexes, high affinity towards ferric ions on CaCO3 surface and slow-release alkaline from CaCO3. A comparison among sodium hydroxide (NaOH), calcium hydroxide (Ca(OH)2) and CaCO3 as additives, was carried out to highlight the advantages of using CaCO3 and clarify the mechanism for the greatly improved performance by a set of characterizations including XRD, FTIR, Zeta potential, XPS, SEM-EDS and TG analyses. The addition of CaCO3 in ferric flocculation resulted in further obvious advantages such as 75% shortened settling time and only one-third of sludge volume of the precipitant, beneficial to the sample handling in engineering application. The proposed new approach has been further confirmed to work efficiently on real phosphonate-containing wastewater. Discussion on the interaction between CaCO3 and ferric salts in phosphonate solutions shed new insights into the working mechanism of using CaCO3 for the treatment of phosphonates-containing wastewater.


Biomonitoring Equivalents for glyphosate.
One of the most widely used herbicides worldwide, glyphosate is registered for use in many agricultural and non-agricultural settings. Accordingly, regulatory authorities develop toxicology reference values (TRVs) to conduct risk assessments for potential exposures. Exposures to glyphosate are typically biomonitored via measures of glyphosate in urine. However, measured concentrations of glyphosate in urine, with units mg/L urine, cannot be directly interpreted using the available TRVs as they are presented in terms of daily intake levels (e.g. mg/kg-bw per day). In this evaluation, we review available health-based risk assessments and TRVs for glyphosate and derive Biomonitoring Equivalent (BE) values for interpretation of population biomonitoring data. Biomonitoring Equivalents (BEs) are defined as the concentration or range of concentrations of a chemical or its metabolite in a biological medium (blood, urine, human milk, etc.) that is consistent with an existing health-based TRVs such as a reference dose (RfD) or tolerable daily intake (TDI). The BE values derived in this manuscript are screening values that can help public health officials and regulators interpret glyphosate biomonitoring data.


The role of copper, molybdenum, selenium, and zinc in nutrition and health.
Copper, zinc, selenium, and molybdenum are involved in many biochemical processes supporting life. The most important of these processes are cellular respiration, cellular utilization of oxygen, DNA and RNA reproduction, maintenance of cell membrane integrity, and sequestration of free radicals. Copper, zinc, and selenium are involved in destruction of free radicals through cascading enzyme systems. Superoxide radicals are reduced to hydrogen peroxide by superoxide dismutases in the presence of copper and zinc cofactors. Hydrogen peroxide is then reduced to water by the selenium-glutathione peroxidase couple. Efficient removal of these superoxide free radicals maintains the integrity of membranes, reduces the risk of cancer, and slows the aging process. On the other hand, excess intake of these trace elements leads to disease and toxicity; therefore, a fine balance is essential for health. Trace element--deficient patients usually present with common symptoms such as malaise, loss of appetite, anemia, infection, skin lesions, and low-grade neuropathy, thus complicating the diagnosis. Symptoms for intoxication by trace elements are general, for example, flu-like and CNS symptoms, fever, coughing, nausea, vomiting, diarrhea, anemia, and neuropathy. A combination of observation, medical and dietary history, and analyses for multiple trace elements is needed to pinpoint the trace element(s) involved. Serum, plasma, and erythrocytes may be used for the evaluation of copper and zinc status, whereas only serum or plasma is recommended for selenium. Whole blood is preferred for molybdenum. When trace element levels are inconsistent with medical evaluations, a test for activity of the suspected enzyme(s) would support the differential diagnosis. Furthermore, it is important to differentiate whether trace element deficiency or toxicity is the primary cause of the disorder, or is secondary to other underlying diseases. Only successful treatment of the primary disorder will lead to complete recovery. In the event of sample contamination during collection or analysis, the physician may be misled by falsely elevated results. Royal blue top evacuated tubes containing negligibly low concentrations of the trace element or acid-washed plastic sterilized syringes should be used for blood, serum, or plasma collection. Powdered gloves must be avoided. When possible, mineral supplements are not to be administered to the patient for a minimum of 3 days prior to sample collection. Serum and plasma specimens are to be transported in acid-washed polypropylene and polyethylene tubes. Analysis is performed in a controlled environment to minimize or eliminate contamination. During analysis, all laboratory wares should be acid-washed for decontamination. A detailed description of these precautions may be found in reviews by Aitio and Jarvisalo and by Chan and Gerson. Copper and zinc analysis on serum and plasma are commonly performed by flame atomic absorption spectrometry, inductively coupled plasma-atomic emission spectrometry, and inductively coupled plasma-mass spectrometry. Serum and plasma selenium levels are determined by graphite furnace atomic absorption with Zeeman background correction and neutron activation analysis. Molybdenum levels are best determined by neutron activation and highly sensitive inductively coupled plasma-mass spectrometry. The reader is referred to reviews by Tsalev and Jarvis.


Suppression of humoral immunity in chickens with carrageenans.
Carrageenans (CGN), sulphated polygalactans, have been reported to be cytotoxic for macrophages in vitro. On this basis, the effect of the 3 major CGN types on humoral immune responses in chickens was investigated. Carrageenan had no effect on body and lymphoid organ weights. Histologically, CGN produced a significant proliferation of reticuloendothelial cells in liver and spleen, but no changes were observed in lymphocyte populations of the bursa of Fabricius, thymus, or spleen. Intracoelomic pretreatment with high doses of CGN induced a marked suppression of primary responses to sheep red blood cells (SRBC) given by the same route. However, if SRBC were injected intravenously into chickens already treated intracoelomically with CGN, no evidence of suppression was demonstrated. Antibody responses to Brucella abortus (BA), a T-independent antigen, were not affected by intracoelomic treatment with CGN. Intravenous pretreatment with CGN did not alter antibody responses to SRBC and BA given by the same route.


Prolonged stabilization of platinum-refractory ovarian cancer in a single patient undergoing long-term Mistletoe extract treatment: Case report.
Advanced ovarian malignancies are associated with poor overall survival; thus, patients often turn to alternative treatments, despite the controversy surrounding their use. Mistletoe extract has been commonly used as complementary medicine to treat patients with cancer for several decades, and has proven benefits in integrative oncology. A 47-year-old woman with stage IVB ovarian cancer who underwent optimal surgical cytoreduction, but whose disease persisted after adjuvant platinum-based combination chemotherapy and 2nd-line chemotherapy. The patient discontinued chemotherapy due to her septic condition and acute kidney injury accompanied by acute pyelonephritis, and opted for adjuvant treatment with mistletoe extract. The patient has achieved good health without progression of cancer or ascites over the 42 months since the 1st diagnosis and 24 months since the last relapse. Our case suggests that mistletoe extract can produce favorable outcomes in patients with platinum-refractory ovarian cancer.


Maternal and child social support and food availability in relation to child growth in four low- and middle-income countries.
Previous studies showed positive associations between specific types of social capital and child nutritional status. Our study examined whether improved food availability mediates the impact of maternal and child social support on child nutritional status in four low- and middle-income countries. We used data from the Young Lives cohort study, comprising 1,000 children aged 8 and 12 in Vietnam and Ethiopia, 1008 in India, and 714 in Peru. The outcome variables were the z-scores for height for age and body mass index (HAZ and BAZ, respectively). The causal mediation analysis framework was used. In Peru, above-median values of maternal social support and receiving child financial support were positively associated with HAZ at age 12. The level of maternal financial support was positively associated with BAZ among 12-year-old children in India. Peru was the only country where a positive association was found between food availability and maternal financial support among children aged 12. However, food availability did not mediate the effect of maternal financial support on HAZ at age 12. Strengthening social support to improve child nutritional status, especially by improving food availability, may not be a sufficient intervention in resource-poor settings because sources of support may lack sufficient food resources to share. However, more comprehensive measurements of social support and food security are necessary to better understand the mechanism of social support and child nutritional status.


Alpha amplitude and phase locking in obsessive-compulsive disorder during working memory.
Alpha event-related desynchronization (ERD) and synchronization are known to reflect brain activation and inhibition, respectively. Alpha phase locking seems to reflect the timing in the cortical process. In a previous study, lower alpha ERD was related to working memory in obsessive-compulsive disorder (OCD) patients than in controls during the retention and retrival phases, but not in the encoding phase. However, memory deficits in OCD patients are known to be related to executive failure during the encoding phase. Thus, focusing on the encoding phase, we tested the level of alpha amplitude and phase locking in OCD patients according to memory load. The EEGs of fifteen OCD patients and fifteen controls were recorded during a Sternberg working memory task. The behavioral performance of the OCD patients was normal. However, the OCD group yielded significantly lower ERD and stronger phase locking. As memory load rose, ERD and phase locking significantly increased in both groups. A difference in event-related alpha oscillation was observed in the encoding phase. Lower alpha modulation in the OCD patient simplied abnormality of the excitatory/inhibitory process in the brain, and increased phase locking might reflect excessive attentional excitability.


Weather conditions during nuptial flights of four European ant species.
In 1977, 1978, and 1979 nuptial flights of Lasius niger L., Lasius flavus F., Myrmica rubra L., and Myrmica scabrinodis Nyl. were observed on the island of Schiermonnikoog and in the area around Amsterdam. Weather conditions during these flights were determined using data from meteorological stations at Schiermonnikoog and Schiphol Airport. Significant differences were found concerning daytime, global radiation and relative humidity at the beginning of flights of Lasius niger, Lasius flavus, and Myrmica rubra; Myrmica scabrinodis had no defined preferences for these parameters. Wind velocity at 2 m of height was less than 1.7 m.s-1 during all flights before 20 August. After that date all species tended to fly at higher wind velocities as well.The calculated ranges for daytime, temperature, global radiation, relative humidity, and wind velocity appeared to be sufficient to characterize all nuptial flight occasions at Schiermonnikoog.Micrometeorological measurements in typical habitats of different ant species revealed that during flights the air temperature at 20 cm above ground and the soil temperature at 5 to 7 cm below ground were about equal in the habitat of the flying species, but unequal in the neighbouring habitats of coexisting ants.


Prevalence and abundance of traditional and host-associated fecal indicators in urban estuarine sediments: Potential implications for estuarine water quality monitoring.
This study aimed to determine the prevalence and abundance of sewage and animal fecal contamination of sediment at seven estuarine locations in Sydney, NSW, Australia. Sediment samples were tested for the occurrence of microbial targets including molecular marker genes of enterococci (ENT), Bacteroides HF183 (HF183), Methanobrevibacter smithii (nifH), human adenovirus (HAdV) and emerging sewage-associated marker genes crAssphage (CPQ_056) and Lachnospiraceae (Lachno3) and animal feces-associated marker genes, including avian feces-associated Helicobacter spp. (GFD), canine-feces associated Bacteroides (DogBact), cattle-feces associated (cowM2) and horse feces-associated Bacteroides (HoF597). Results from this study showed that urban estuarine sediment can act as a reservoir of fecal indicator bacteria (FIB) and several microbial source tracking (MST) marker genes, including previously unreported Lachno3. The sewage-associated marker gene CPQ_056 was most prevalent, in 63.8% of sediment samples, while the avian associated marker gene GFD had the highest mean abundance. The GFD marker gene was highly abundant and widely detected in sediment samples from all seven locations compared to the other animal feces-associated marker genes. In all, 31 (44.9%) sediment samples were positive for at least two sewage-associated marker genes. However, the non-quantifiable detection of the HAdV marker gene did not always align with the detection of two or more sewage-associated marker genes. In addition, the most frequent wet weather overflow exposure occurred at locations that did not have a consistent pattern of detection of the sewage-associated marker genes, suggesting sediments may not be a suitable measure of recent sewage contamination. To assist water quality and public health managers better understand past microbial contamination of estuarine sediment, further studies seem justified to explore the role of decay of MST marker genes in sediment. Further work is also needed on the role of resuspension of MST marker genes from sediment during storm events to the water column as a source of contamination for both the GFD and sewage-associated marker genes.


Enhancing biofilm formation in biofilters for benzene, toluene, ethylbenzene, and xylene removal by modifying the packing material surface.
Polyurethane (PU) sponges are popular packing material in biofilters and their smooth and hydrophobic surface often leads to an uneven distribution and detachment of biofilms. In this work, the surface of PU sponge was modified to obtain higher roughness and positive charge. The performances of two biofilters (BF1 with pristine sponge and BF2 with modified sponge) for benzene, toluene, ethylbenzene, and xylene (BTEX) removal were investigated. Total Volatile Organic Compound (TVOC) removal efficiency and CO2 increment were 61% and 804 ppm for BF2 respectively after start-up, compared with 51% and 538 ppm for BF1. Analysis on biofilms showed that the modification of PU sponge significantly improved the microbial growth, viability and adhesive strength in biofilms, reduced extracellular polymeric substance (EPS) and changed the microbial community. These results demonstrate that modified sponge can enhance biofilm formation and BTEX removal in biofilters and may applied in large-scale applications.


[Structured treatment of diabetes in the country].
The aim of the DIALA project was to demonstrate the feasibility of structured treatment and teaching programs for type 2 diabetic patients in order to improve the overall quality of care. The investigation was carried out in Upper Austria. The results and findings of structured treatment were evaluated as well as the associated costs of current diabetes management. 19 practitioners were recruited. From the beginning of January 2002 to the end of December 2003, a total of 343 diabetics were registered, and clinical and economic data were collected on all diabetic patients who visited the primary care offices during the period of 24 months. The aims of treatment were discussed between practitioners and patients, routine examinations were carried out quarterly, and all data were recorded using a diabetes care card. All the patients participating in the project were given the opportunity to take part in a diabetes self-management teaching programme. There was an obvious correlation between information and treatment on the one hand and clinical results, as measured by HbA1c, blood pressure levels and body weight on the other. Costs were calculated in a standardized way, and showed a reduction in expense as a result of the structured treatment and cost savings amounting to EUR 620 per annum and patient. The hospital admission rate for cases with diabetes mellitus as the primary diagnosis was considerably reduced. Our results indicate that establishing a structured treatment and teaching programme can improve the quality of diabetes therapy in primary care and influence the rate at which physicians admit patients to hospital.


Computed diffusion-weighted MR imaging for visualization of pancreatic adenocarcinoma: Comparison with acquired diffusion-weighted imaging.
To assess the feasibility of computed diffusion-weighted imaging (cDWI) in comparison with directly acquired DWI for visualizing pancreatic adenocarcinomas. Patients with pancreatic adenocarcinoma underwent DWI at b-values of 0, 1000 (DWI1000), 1500 (DWI1500) and 2000 (DWI2000) s/mm2. From DWIs at b-values of 0 and 1000s/mm2, we generated cDWIs at b-values of 1500 (cDWI1500) and 2000 (cDWI2000) s/mm2. DWI findings of pancreatic adenocarcinomas (clear hyperintensity; hyperintensity with an unclear distal border; and isointensity), the image quality and the tumor to pancreas contrast ratio (CR) were compared between directly acquired DWI and cDWI. Among the 63 included patients, clear hyperintense tumors were seen in 35 on DWI1000, 50 on DWI1500, 50 on cDWI1500, 53 on DWI2000 and 44 on cDWI2000. Incidence of clear hyperintense tumors was significantly higher on cDWI1500 than on DWI1000 (P=0.013). There was no significant difference in the incidence of clear hyperintense tumors between DWI1500 and cDWI1500 (P>0.999), but a lower incidence was seen on cDWI2000 than on DWI2000 (P=0.028). Image quality was lower on cDWI than on DWI at b-values of 1500 (P=0.002) and 2000s/mm2 (P<0.001). The tumor to distal pancreas CR was significantly higher on cDWI2000 than on cDWI1500 (P<0.001), and on cDWI1500 than on DWI1000 (P<0.001). The cDWI showed a significantly higher tumor to distal pancreas CR than DWI at b-values of 1500 (P=0.004) and 2000s/mm2 (P<0.001). cDWI1500 generated from b-values of 0 and 1000s/mm2 should be considered more effective than DWI1000 and at least as effective as DWI1500.


New Developments in the Pathogenesis, Therapeutic Targeting, and Treatment of Pediatric Medulloblastoma.
Pediatric medulloblastoma (MB) is the most common pediatric brain tumor with varying prognoses depending on the distinct molecular subtype. The four consensus subgroups are WNT, Sonic hedgehog (SHH), Group 3, and Group 4, which underpin the current 2021 WHO classification of MB. While the field of knowledge for treating this disease has significantly advanced over the past decade, a deeper understanding is still required to improve the clinical outcomes for pediatric patients, who are often vulnerable in ways that adult patients are not. Here, we discuss how recent insights into the pathogenesis of pediatric medulloblastoma have directed current and future research. This review highlights new developments in understanding the four molecular subtypes' pathophysiology, epigenetics, and therapeutic targeting. In addition, we provide a focused discussion of recent developments in imaging, and in the surgery, chemotherapy, and radiotherapy of pediatric medulloblastoma. The article includes a brief explanation of healthcare costs associated with medulloblastoma treatment.


Psychological immune competency predicts burnout syndrome among the high-risk healthcare staff: A cross-sectional study.
Burnout and psychological immune competency have not been investigated together among employees of high-risk specializations such as emergency medicine, intensive care or surgery. In this study we aim to examine the prevalence of burnout among high-risk clinical staff and explore whether the strength of psychological immune competency predict burnout. A cross-sectional design utilizing a self-administrated questionnaire was used to collect data from the participants (n = 216). Nurses (n = 145) and physicians (n = 71) from emergency medicine, intensive care and surgery departments participated in the study. Burnout syndrome was measured using the Maslach Burnout Inventory, while psychological immune competency was measured using the Psychological Immune Competency Questionnaire. The data collection started in June of 2018 and was finished in March of 2019. Participants with higher psychological immune competency reported lower levels of burnout: emotional exhaustion (r = -0.478; p < 0.001), depersonalization (r = -0.459; p < 0.001) and personal accomplishment (r = 0.543; p < 0.001). Multiple linear stepwise regression analysis revealed the psychological immune competency to be a stable predictor of burnout on all three scales. Psychological immune competency shows a strong relationship with scales of burnout syndrome and as such should be further examined due to development of successful intervention and prevention programs.


The validity of the estimates of the half-saturation concentration and maximum velocity for the efflux of glucose from human erythrocytes in infinite-cis conditions.
It is shown that, if the asymmetrical model for glucose transport is correct, the published estimates of this half-saturation concentration must be low. As a result, the model is even less able than before to satisfy the tests of its validity.


Degradation pathways study of the natriuretic and β-adrenoceptor antagonist tienoxolol using liquid chromatography-electrospray ionization multistage mass spectrometry.
Tienoxolol is a pharmacologically active molecule designed with the functional groups ketothiophene, alkyl benzoate and arylpropanolamine so as to combine a diuretic and a β-adrenoreceptor antagonist into a single molecule. Its degradation products generated in several stress media have been determined by high-pressure liquid chromatography (HPLC) coupled to a hybrid mass spectrometer with a triple quadrupole-linear trap. A Polaris(®) column with a C18-A stationary phase and a linear gradient mobile phase composed of a mixture of trifluoroacetic acid 1% (v/v) and acetonitrile allowed for optimal separation. Structural elucidation of the degradation products has been based on MS/MS techniques, by comparing their fragmentation patterns to the precursor's data. Up to seven degradation products of the active ingredient, resulting from hydrolysis, oxidation, dehydration and transamidation have been identified, covering a range of possible degradation pathways for derivatives with such functional groups. Kinetics have been studied to assess the molecule's shelf life and to identify the most important degradation factor.


Effects of the NMDA antagonist ketamine on task-switching performance: evidence for specific impairments of executive control.
In humans, the effects of subanesthetic doses of ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, substantially impair executive control functions. Here, we consider whether ketamine exposure can provide an animal model for the effects of ketamine on executive control. Two monkeys (Macaca mulatta) performed a cued task-switching paradigm. We studied their behavior before and after a range of ketamine doses. We found that ketamine slowed overall performance and decreased overall accuracy, strongly impaired the capacity to ignore task-irrelevant information and, to a lesser degree, decreased accuracy when a task switch was required. This pattern of results is very similar to that found in studies of schizophrenic patients performing task-switching paradigms or the Stroop task. We conclude that ketamine in monkeys provides a good animal model for exploring the relationship between the glutamate system, executive control, and the symptoms of schizophrenia.


Understanding the Cryoglobulinemias.
Cryoglobulins are immunoglobulins with the ability to precipitate at temperatures <37 °C. They are related to hematological disorders, infections [especially hepatitis C virus (HCV)], and autoimmune diseases. In this article, the state of the art on Cryoglobulinemic Vasculitis (CV), in a helpful and schematic way, with a special focus on HCV related Mixed Cryoglobulinemia treatment are reviewed. Direct - acting antivirals (DAA) against HCV have emerged as an important key in HCV treatment to related Cryoglobulinemic Vasculitis, and should be kept in mind as the initial treatment in non-severe manifestations. On the other hand, a recent consensus panel has published their recommendations for treatment in severe and life threatening manifestations of Mixed Cryoglobulinemias. HCV-Cryoglobulinemic vasculitis is the most frequent form of CV. There are new treatment options in HCV-CV with DAA, with an important number of patients achieving complete response and sustained virologic response (SVR). In cases of severe forms of CV, treatment with Rituximab and PLEX are options. The lack of data on maintenance therapy could impulse future studies in this setting.


Phototherapy-induced hypocalcemia and hypoparathyroidism in icteric term newborns.
Phototherapy is demonstrated to cause hypocalcemia by decreasing melatonin levels and increasing cortisol levels. However, the relationship between parathyroid hormone (PTH) level and calcium has not been previously evaluated in patients receiving phototherapy. Our study aimed to evaluate the effect of phototherapy on ionized calcium (iCa), total calcium (tCa), corrected calcium (cCa), magnesium (Mg), phosphorus (P), 25-hydroxyvitamin D (25(OH)D), and PTH levels. Infants who were born at term and received inpatient phototherapy for indirect hyperbilirubinemia were included in our study. The patients' gestational age, birth weight, and phototherapy durations were recorded. Total bilirubin, albumin, iCa, tCa, cCa, Mg, 25(OH)D, and PTH levels before and after phototherapy were compared. Laboratory results were also compared between patients who received phototherapy for ≤24 h, 25-47 h, and ≥48 h. A total of 166 term infants were included in the study. The mean duration of phototherapy was 31.9 ± 9.2 h. Albumin levels before and after phototherapy were similar (p=0.246). However, there were significant decreases in iCa, tCa, cCa, Mg, 25(OH)D, and PTH levels after phototherapy (p<0.001), while P level was significantly increased after phototherapy (p<0.001). In addition, P levels increased with >24 h of phototherapy, while iCa, tCa, cCa, Mg, 25(OH)D, and PTH levels decreased significantly with ≥48 h of phototherapy (p=0.002, p=0.008, p=0.001, p=0.012, and p<0.001, respectively). This study demonstrates that PTH suppression is one of the causes of phototherapy-induced hypocalcemia.


Tuberculin skin test results and the booster phenomenon in two-step tuberculin skin testing in hemodialysis patients.
Patients with chronic renal failure are at increased risk for tuberculosis (TB). Centers for Disease Control and Prevention (CDC) have recommended annual skin testing for TB, with tuberculin-purified protein derivative (PPD), in patients with chronic renal failure. Uremia alters the macrophage function, which can lead to anergy for skin tests. The aim of this prospective study was to determine the prevalence of positive tuberculin skin test (TST) and the booster effect of TST in hemodialysis patients living in a relatively underdeveloped portion of the country. Material and Methods. Patients were recruited from Van (Yuzuncu Yil University Hospital, Yuksek Ihtisas Hospital) and the Mus State Hospital). At the time of this study, a total of 143 patients were under hemodialysis treatment in these hemodialysis centers, and among them, 124 were included in the study. Informed consent was obtained before inclusion in the study. A positive PPD was an induration of >10 mm in response to five tuberculin units of PPD (RT23-Tween 80), at 72 h. TST-negative patients received a booster TST 10 days later, approximately 10 cm away from the previous intracutaneous injection. The test dose could not be increased due to unavailability of this kind of preparation. The test was performed and interpreted in the same way. Skin testing was performed in June and December 2003. Patients with known active TB are not included in the study. Testing was not done in hospitalized patients to rule out effects of other disease states. Results. Mean age of the patients was 45.3 +/- 16 (range 13-82) years. All patients were on HD treatment twice (n: 14) or three times (n: 110) weekly. Duration of dialysis before TST was 30 +/- 17 (12-84) months. With the first test (n: 14), 11.3% of the patients showed a positive reaction; the second test added (n: 15) 12.1% more TST-positive patients, reaching a total of (n: 29) 23.4% of the patients with a positive TST. The


Live-attenuated ME49Δcdpk3 strain of Toxoplasma gondii protects against acute and chronic toxoplasmosis.
Toxoplasmosis, a common parasitic disease, is caused by Toxoplasma gondii, which infects approximately 30% of the world's population. This obligate intracellular protozoan causes significant economic losses and poses serious public health challenges worldwide. However, the development of an effective toxoplasmosis vaccine in humans remains a challenge to date. In this study, we observed that the knockout of calcium-dependent protein kinase 3 (CDPK3) in the type II ME49 strain greatly attenuated virulence in mice and significantly reduced cyst formation. Hence, we evaluated the protective immunity of ME49Δcdpk3 as a live attenuated vaccine against toxoplasmosis. Our results showed that ME49Δcdpk3 vaccination triggered a strong immune response marked by significantly elevated proinflammatory cytokine levels, such as IFN-γ, IL-12, and TNF-α, and increased the percentage of CD4+ and CD8+ T-lymphocytes. The high level of Toxoplasma-specific IgG was maintained, with mixed IgG1/IgG2a levels. Mice vaccinated with ME49Δcdpk3 were efficiently protected against the tachyzoites of a variety of wild-type strains, including type I RH, type II ME49, Chinese 1 WH3 and Chinese 1 WH6, as well as the cysts of wild-type strains ME49 and WH6. These data demonstrated that ME49Δcdpk3 inoculation induced effective cellular and humoral immune responses against acute and chronic Toxoplasma infections with various strains and was a potential candidate to develop a vaccine against toxoplasmosis.


Influence of pharmacologic agents on tissue metabolism in circulatory shock.
Our research activities have been oriented to the effect of pharmacologic agents on tissue metabolism in the low flow state of circulatory shock. Specifically, we have been most interested in the effect of glucocorticoids on cellular metabolism because these agents exert a reproducible protective effect during septic and endotoxic shock in rats and monkeys. Further, we have studied the differences between untreated animals in shock and those treated with pharmacologic agents in an attempt to determine which cellular metabolic changes are critical to survival. This paper will present our studies as well as those of other laboratories, which have defined the effects on tissue metabolism of certain pharmacologic agents: those which stimulate cyclic adenosine monophosphate (AMP) (epinephrine, norepinephrine, glucagon, and prostaglandin) and those which do not (the glucocorticoids).


Influence of graft vascularization on graft survival following homologous limbo-keratoplasty.
Limbo-keratoplasty enables visual improvement and limbal stem cell transplantation at the same. During follow-up, most grafts show vascularization of the limbus. However, it is unclear whether vascularization is harmful due to immunologic effects or helpful to nourish the limbal stem cells and is therefore necessary for a clear graft. The aim of our study is to analyze the influence of graft vascularization on graft survival following homologous limbo-keratoplasty. In this retrospective study, we assessed all consecutive limbo-keratoplasties performed in our hospital. All eyes with suitable photo-documentation were included and divided into two groups (limbal stem cell deficiency and corneal dystrophy). We categorized the grade of vascularization (0, 1, 2, 3, 3b) and analyzed clear graft survival, recurrence of the underlying disease and the endothelial cell density (ECD) with regard to the reason for the graft. Event rates were estimated with the Kaplan-Meier method. A total of 79 eyes with limbal stem cell deficiency and 15 with corneal dystrophies were analyzed. A high degree of graft vascularization had a tendency for better graft survival in limbal stem cell deficiency, whereas in corneal dystrophies, grafts with no vascularization had preferable outcomes. Recurrence-free graft survival was only seen in grade 1 and 3 vascularization in corneal dystrophies. Vascularization of the limbus seems to have an impact on the long-term outcome of limbo-keratoplasty. The effect seems to be favorable in limbal stem cell deficiency and on recurrence rates in corneal dystrophies. However, the latter might be overshadowed by an unfavorable immunologic effect in corneal dystrophies where the baseline immunologic risk profile is commonly more favorable than in limbal stem cell deficiency.


In vitro copper-chelating properties of flavonoids.
Copper is an indispensable trace element for human body and the association between a disruption of copper homeostasis and a series of pathological states has been well documented. Flavonoids influence the human health in a complex way and the chelation of transient metal ions indisputably contributes to their mechanism of the action, however, the information about their copper-chelating properties have been sparse. This in vitro study was thus aimed at the detailed examination of flavonoids-copper interactions by two spectrophotometric assays at four (patho)physiologically relevant pH conditions (4.5-7.5), with the emphasis on the structure-activity relationship. The tested flavonoids were compared with the clinically used copper chelator, trientine. Most of the 26 flavonoids chelated copper ions, however, in a variable extent. Only flavones and flavonols were able to form stable complexes with both cupric and cuprous ions. The 3-hydroxy-4-keto group and 5,6,7-trihydroxyl group represented the most efficient chelation sites in flavonols and flavones, respectively, and the 2,3-double bond was essential for the stable copper chelation. Interestingly, the 3´,4´-dihydroxyl (catechol) group was associated only with a weak activity. Although none of the tested flavonoids were more potent than trientine at physiological or slightly acidic conditions, 3-hydroxyflavone, kaempferol and partly baicalein surpassed trientine at acidic conditions. Conclusively, flavonoids containing appropriate structural features were efficient copper chelators and some of them were even more potent than trientine under acidic conditions.


Correction: Surface induced smectic order in ionic liquids - an X-ray reflectivity study of [C22C1im]+[NTf2]<sup/>.
Correction for 'Surface induced smectic order in ionic liquids - an X-ray reflectivity study of [C22C1im]+[NTf2]-' by Julian Mars et al., Phys. Chem. Chem. Phys., 2017, 19, 26651-26661.


Glycogen synthesis from glucose by direct and indirect pathways in hepatocyte cultures from different nutritional states.
The conversion of glucose to glycogen by direct and indirect pathways was determined from the incorporation of [6-3H,U-14C]glucose into glycogen in hepatocyte cultures isolated from fed, fasted or fasted-refed rats. Mercaptopicolinate, an inhibitor of phosphoenolpyruvate carboxykinase (PEPCK) was used to determine the extent by which 6-tritium is lost by mechanisms not involving flux through PEPCK. Glucose conversion to glycogen was lower in hepatocytes from fasted and higher in hepatocytes from fasted-refed rats than in hepatocytes from rats fed ad libitum. Insulin increased glycogen synthesis in hepatocytes from all nutritional states, and it decreased the 3H/14C ratio incorporated into glycogen. This increased loss of 6-tritium was only in part mercaptopicolinate-sensitive. Lactate and pyruvate (2 mM + 0.2 mM) increased glycogen deposition, largely by stimulation of glucose conversion to glycogen by the direct pathway. Insulin-induced glucokinase mRNA expression was higher in hepatocytes from fed than from fasted or refed rats whereas PEPCK mRNA expression was lowest in hepatocytes from fasted-refed rats. Hepatocyte cultures derived from different nutritional states express differences in glycogen synthesis from glucose by direct and indirect pathways as well as differences in the extent by which pyruvate cycling accounts for loss of 6-tritium.


Approaches to Cough Peak Flow Measurement With Duchenne Muscular Dystrophy.
Manually-assisted coughing and mechanical insufflation-exsufflation (MI-E) are commonly used in patients with Duchenne muscular dystrophy (DMD). Few studies have compared cough peak flow (CPF) with manually-assisted coughing to other methods, such as MI-E + manually-assisted coughing. In addition, few studies have reported the reliability of the measured CPF values. This study aimed to compare CPF with different cough-assistance methods and to examine the reliability of CPF data. The study included 12 subjects with DMD (mean age, 34 ± 8 y). CPF, CPF + manually-assisted coughing (assisted CPF), maximum insufflation capacity (MIC) + CPF (MIC-CPF), MIC + manually-assisted coughing (MIC+assisted CPF), MI-E (MI-E-CPF), and MI-E + assisted CPF were measured. A spirometer was used to compare CPF measurements obtained with each of the cough-assist techniques. The reliability of the measured CPF values was analyzed using Bland-Altman analysis. CPF was 59 ± 34 L/min, assisted CPF was 113 ± 32 L/min, MIC-CPF was 170 ± 30 L/min, MIC+assisted CPF was 224 ± 62 L/min, MI-E-CPF was 199 ± 40 L/min, and MI-E + assisted CPF was 240 ± 38 L/min. A fixed and proportional bias was found in the CPF measurements made with the peak flow meter and the spirometer. The average 95% CI in the difference between peak flow meter, MI-E, and CPF obtained using the spirometer were -7.45 to -1.95 and -1.45 to 4.95, respectively. Test for correlation was r = 0.54 (P < .001) for CPF (peak flow meter) and CPF (spirometer) and r = 0.17 (P = .17) in CPF (MI-E) and CPF (spirometer), respectively. MI-E + assisted CPF was the highest. The CPF measured with the peak flow meter suggested underestimation.


Reassessment of echocardiographic criteria for diagnosis of mitral valve prolapse.
Commonly used echocardiographic criteria for mitral valve prolapse (MVP) include a sizable proportion of persons whose hearts are normal. Nevertheless, the echocardiogram is generally used as an independent standard for the diagnosis of MVP despite lack of consensus on the criteria to be used and the probability of interobserver variability. Conversely, there is a relatively uniform consensus that classic auscultatory signs establish the diagnosis of MVP beyond reasonable doubt. Accordingly, in 148 patients referred for evaluation of known or suspected MVP, the echocardiographic patterns that coincide with diagnostic auscultatory signs were studied prospectively to compare those patterns with criteria commonly used for the echocardiographic diagnosis of MVP and to determine interobserver variability in echocardiographic interpretation. Eighty patients (54%) had a classic mid- to late systolic click or an apical late systolic murmur, or both. Eleven patients (7%) had the apical holosystolic murmur of mitral regurgitation with no discernible clinical or echocardiographic cause other than the consideration of MVP. Doppler echocardiography was performed in 80 of the 148 patients. The degree of superior systolic bowing of each mitral leaflet and the location of leaflet coaptation relative to the presumed plane of the mitral anulus were graded on apical 4-chamber and parasternal long-axis views. The only patterns absolutely specific for auscultatory MVP were: severe bowing of the anterior or posterior leaflet; coaptation of leaflets on the left atrial side of the anular plane; moderate to severe Doppler mitral regurgitation accompanied by any degree of leaflet bowing; and mild Doppler mitral regurgitation accompanied by moderate bowing of a leaflet.(ABSTRACT TRUNCATED AT 250 WORDS)


New suspension-feeding radiodont suggests evolution of microplanktivory in Cambrian macronekton.
The rapid diversification of metazoans and their organisation in modern-style marine ecosystems during the Cambrian profoundly transformed the biosphere. What initially sparked this Cambrian explosion remains passionately debated, but the establishment of a coupling between pelagic and benthic realms, a key characteristic of modern-day oceans, might represent a primary ecological cause. By allowing the transfer of biomass and energy from the euphotic zone-the locus of primary production-to the sea floor, this biological pump would have boosted diversification within the emerging metazoan-dominated benthic communities. However, little is known about Cambrian pelagic organisms and their trophic interactions. Here we describe a filter-feeding Cambrian radiodont exhibiting morphological characters that likely enabled the capture of microplankton-sized particles, including large phytoplankton. This description of a large free-swimming suspension-feeder potentially engaged in primary consumption suggests a more direct involvement of nekton in the establishment of an oceanic pelagic-benthic coupling in the Cambrian.


DNA-protein crosslinks processed by nucleotide excision repair and homologous recombination with base and strand preference in E. coli model system.
Bis-electrophiles including dibromoethane and epibromohydrin can react with O(6)-alkylguanine-DNA alkyltransferase (AGT) and form AGT-DNA crosslinks in vitro and in vivo. The presence of human AGT (hAGT) paradoxically increases the mutagenicity and cytotoxicity of bis-electrophiles in cells. Here we establish a bacterial system to study the repair mechanism and cellular responses to DNA-protein crosslinks (DPCs) in vivo. Results show that both nucleotide excision repair (NER) and homologous recombination (HR) pathways can process hAGT-DNA crosslinks with HR playing a dominant role. Mutation spectra show that HR has no strand preference but NER favors processing of the DPCs in the transcribed strand; UvrA, UvrB and Mfd can interfere with small size DPCs but only UvrA can interfere with large size DPCs in the transcribed strand processed by HR. Further, we found that DPCs at TA deoxynucleotide sites are very inefficiently processed by NER and the presence of NER can interfere with these DNA lesions processed by HR. These data indicate that NER and HR can process DPCs cooperatively and competitively and NER processes DPCs with base and strand preference. Therefore, the formation of hAGT-DNA crosslinks can be a plausible and specific system to study the repair mechanism and effects of DPCs precisely in vivo.


Auditory evoked brain potentials as markers of chronic effects of mild traumatic brain injury in mid-life.
Auditory event-related potential (ERP) correlates of pre-dementia in late-life may also be sensitive to chronic effects of mild traumatic brain injury (mTBI) in mid-life. In addition to mTBI history, other clinical factors may also influence ERP measures of brain function. This study's objective was to evaluate the relationship between mTBI history, auditory ERP metrics, and common comorbidities. ERPs elicited during an auditory target detection task, psychological symptoms, and hearing sensitivity were collected in 152 combat-exposed veterans and service members, as part of a prospective observational cohort study. Participants, with an average age of 43.6 years, were grouped according to positive (n = 110) or negative (n = 42) mTBI history. Positive histories were subcategorized into repetitive mTBI (3 + ) (n = 40) or non-repetitive (1-2) (n = 70). Positive history of mTBI was associated with reduced N200 amplitude to targets and novel distractors. In participants with repetitive mTBI compared to non-repetitive and no mTBI, P50 was larger in response to nontargets and N100 was smaller in response to nontargets and targets. Changes in N200 were mediated by depression and anxiety symptoms and hearing loss, with no evidence of a supplementary direct mTBI pathway. Auditory brain function differed between the positive and negative mTBI groups, especially for repetitive injury, which implicated more basic, early auditory processing than did any mTBI exposure. Symptoms of internalizing psychopathology (depression and anxiety) and hearing loss are implicated in mTBI's diminished brain responses to behaviorally relevant and novel stimuli. A mid-life neurologic vulnerability conferred by mTBI, particularly repetitive mTBI, may be detectable using auditory brain potentials, and so auditory ERPs are a target for study of dementia risk in this population.