Mechanistic movement models identify continuously updated autumn migration cues in Arctic caribou.
Migrations in temperate systems typically have two migratory phases, spring and autumn, and many migratory ungulates track the pulse of spring vegetation growth during a synchronized spring migration. In contrast, autumn migrations are generally less synchronous and the cues driving them remain understudied. Our goal was to identify the cues that migrants use in deciding when to initiate migration and how this is updated while en route. We analyzed autumn migrations of Arctic barren-ground caribou (Rangifer tarandus) as a series of persistent and directional movements and assessed the influence of a suite of environmental factors. We fitted a dynamic-parameter movement model at the individual-level and estimated annual population-level parameters for weather covariates on 389 individual-seasons across 9 years. Our results revealed strong, consistent effects of decreasing temperature and increasing snow depth on migratory movements, indicating that caribou continuously update their migratory decision based on dynamic environmental conditions. This suggests that individuals pace migration along gradients of these environmental variables. Whereas temperature and snow appeared to be the most consistent cues for migration, we also found interannual variability in the effect of wind, NDVI, and barometric pressure. The dispersed distribution of individuals in autumn resulted in diverse environmental conditions experienced by individual caribou and thus pronounced variability in migratory patterns. By analyzing autumn migration as a continuous process across the entire migration period, we found that caribou migration was largely related to temperature and snow conditions experienced throughout the journey. This mechanism of pacing autumn migration based on indicators of the approaching winter is analogous to the more widely researched mechanism of spring migration, when many migrants pace migration with a resource wave. Such a similarity in mechanisms highlights the different environmental stimuli to which migrants have adapted their movements throughout their annual cycle. These insights have implications for how long-distance migratory patterns may change as the Arctic climate continues to warm.


Serotonergic activation of tonic-type enteric neurons in guinea pig small bowel.
1. Electrical stimulation of interganglionic fiber tracts of Auerbach's plexus released a chemical substance, which produced a slow EPSP associated with an increase in input resistance in the postsynaptic neuron. 2. This effect of fiber tract stimulation was mimicked by microiontophoretic application of serotonin (5-HT) to the neurons. Both the endogenous transmitter substance and exogenous 5-HT produced membrane depolarization, both increased the input resistance of the neuron, both reduced or abolished hyperpolarizing afterpotentials of the action potentials, and both augmented membrane excitability. 3. During tachyphylaxis to excess 5-HT (1 micron) in the perfusion solution, the response to fiber tract stimulation was also reversibly blocked. 4. Methysergide (30 micron) blocked both the response to fiber tract stimulation and to exogenous 5-HT. 5. Cholinergic agonists and antagonists did not alter the slow EPSP and the response to exogenous 5-HT. 6. The evidence suggests that 5-HT is the neurotransmitter substance that produces the slow EPSP in myenteric neurons.


Do dispersing non-reproductive female Damaraland mole-rats, Cryptomys damarensis (Rodentia: Bathyergidae) exhibit spontaneous or induced ovulation?
The Damaraland mole-rat is a eusocial, subterranean rodent that exhibits a seasonal breeding. Non-reproductive females show physiological suppression of reproduction whilst in the confines of the natal colony. This study set out to investigate whether dispersing female Damaraland mole-rats exhibit induced or spontaneous ovulation. Fifteen non-reproductive females were removed from their natal colonies and housed individually for a period of 6 weeks. During this period urine was collected from all animals every second day. After this initial period the animals were divided into 3 groups. Females were subjected to 1 of 3 trials: a control group housed separately without a male, allowed non-physical contact, or placed in direct physical contact with vasectomized males. Urine was collected for a further 5 weeks, and urinary progesterone profiles established. All three groups showed a significant difference in urinary progesterone concentrations between the two treatment periods indicating initiation of follicular development in all animals following removal from the colony. Histological results further revealed that at least one animal in the control group and five of the six animals in the vasectomized group had corpora lutea present in the ovaries showing that ovulation has taken place. All groups had similar numbers of Graafian follicles, indicating that all females were likely to ovulate in the near future. This finding suggests that females are capable of spontaneous ovulation, but the act of coitus may advance the onset of ovulation in this arid dwelling mole-rat.


Noninvasive multidetector computed tomography enterography in patients with small-bowel Crohn's disease: is a 40-second delay better than 70 seconds?
Multidetector computed tomography (MDCT) enterography combines neutral enteric contrast with intravenously administered contrast material. The optimal intravenous (IV) contrast material protocol has still not been established. To determine the optimal delay time to image patients with small-bowel Crohn's disease during MDCT enterography. After oral administration of 1350 ml of neutral contrast medium, 26 patients with small-bowel Crohn's disease underwent MDCT enterography;scans were obtained 40 s (enteric phase) and 70 s (parenchymal phase) after IV administration of 100 ml of iodinated contrast material. Three radiologists, blinded to clinical and pathological findings, independently and retrospectively evaluated each scan in two separate reading sessions for the presence or absence of CT features of Crohn's disease activity. The interobserver agreement was evaluated, and the efficacy of each phase in detecting active disease in the terminal ileum for each reader was determined. The gold standard was pathology (n=13), endoscopy (n=3), and clinical evaluation (n=10). No statistically significant difference was present between the enteric and the parenchymal phase for each reader in each segment regarding the presence or absence of CT features of Crohn's disease. The interobserver agreement for the presence of five main features of active Crohn's disease in the terminal ileum ranged from poor to excellent.The sensitivity, specificity, negative predictive value, positive predictive value, and accuracy for active Crohn's disease in the terminal ileum ranged from 40 to 90%, 88 to 100%, 70 to 94%, 44 to 100%, and 69 to 96%, respectively. There was no statistical difference between the two phases for each reader. MDCT enterography in patients with suspected active Crohn's disease can be obtained at either 40 s or 70 s after IV contrast material.


Correlation between the size of song control nuclei and plumage color change in orange bishop birds.
Adult male orange bishop birds (Euplectes franciscanus) develop beautiful nuptial plumage during the breeding season, but have the same sober plumage as the female during the non-breeding season. The male conspecific song is highly stereotyped during nuptial plumage. Large volume differences were found in two song control nuclei in the cerebrum between the male and female during the breeding season, and in the same nuclei of the males during the breeding and non-breeding seasons. The seasonal changes in the size of cerebral song control nuclei were dominant in the male and may not correlate with the improvement or modification of the song repertories.


An assessment of the safety, hemostatic efficacy, and clinical impact of low-titer group O whole blood in children and adolescents.
Low-titer group O whole blood (LTOWB) use has been associated with improved survival and less blood transfusions in adult trauma patients. Its use in pediatric trauma has been shown to be safe when using leukoreduced, LTOWB with anti-A, anti-B antibody titers of <1:50. We set out to evaluate the safety, hemostatic potential, and impact on pediatric outcomes at a center using non-leukoreduced, LTOWB with anti-A, anti-B antibody titers of <1:200. Patients younger than 18 years, who received emergency-release, uncrossed matched blood, and presented to our trauma center from November 2017 to April 2021 were included. Patients were divided into those receiving any LTOWB and those receiving only RBC and or plasma (COMP). Primary outcome was 30-day survival. One hundred sixty-four patients received emergency release blood products. Of these, 73 received at least one unit of LTOWB. The LTOWB group were younger (14 years vs. 13 years), more likely to be male (87% vs. 49%), and to have sustained penetrating trauma (44% vs. 23%); all p < 0.05. Low-titer group O whole blood patients received more blood than their COMP counterparts prior to arrival. Serial hemolysis panels (K+, bilirubin, LDH, haptoglobin) obtained at 24 hours, 48 hours, and 72 hours were similar between groups; all p > 0.05. There was no difference in survival by univariate analysis but after adjusting for inverse probability of treatment weights there was an observed association between WB administration and improved survival, with an odds ratio of 2.48 (1.15-5.47). Non-leukoreduced, LTOWB in anti-A/anti-B antibody titers of <1:200 appear safe in children and adolescents. While patients receiving LTOWB had more evidence of shock, higher torso injury severity, and received more prehospital blood products, there may be a mortality benefit with whole blood. Larger, multicenter studies are needed. Therapeutic/Care Management; Level IV.


Field dependence and reaction time in senior tennis players (65 and over).
Rod-and-frame errors and speed of response are both thought to reflect, in part, differential ability in selective attention, or one's ability to focus on the salient perceptual factors of a given environment. The present study involved an investigation of 18 "super-senior" tennis players aged 70 yr. and over who participated in the national championship tournament. Their data were compared with the data from a similar aged heterogeneous group. The super-seniors were significantly more field independent and had much more rapid simple reaction times and total-body response time than their counterparts.


Identification of F-box gene family in Brassica oleracea and expression analysis in response to low-temperature stress.
Unfavorable climatic conditions, such as low temperatures, often hinder the growth and production of crops worldwide. The F-box protein-encoding gene family performs an essential role in plant stress resistance. However, a comprehensive analysis of the F-box gene family in cabbage (Brassica oleracea var capitata L.) has not been reported yet. In this study, genome-wide characterization of F-box proteins in cabbage yielded 303 BoFBX genes and 224 BoFBX genes unevenly distributed on 9 chromosomes of cabbage. Phylogenetic analysis of 303 BoFBX genes was classified into nine distinct subfamily groups (GI-GIX). Analysis of the gene structure of BoFBX genes indicated that most genes within the same clade are highly conserved. In addition, tissue-specific expression analysis revealed that six F-box genes in cabbage showed the highest expression in rosette leaves, followed by roots and stems and the lowest expression was observed in the BoFBX156 gene. In contrast, the expression of the other five genes, BoFBX100, BoFBX117, BoFBX136, BoFBX137 and BoFBX213 was observed to be upregulated in response to low-temperature stress. Moreover, we found that the expression level of the BoFBX gene in the cold-tolerant cultivar "ZG" was higher than that in cold-sensitive "YC" with the extension of stress duration, while expression levels of each gene in "ZG" were higher than "YC" at 24 h. Knowledge of the various functions provided by BoFBXs genes and their expression patterns provides a firm theoretical foundation for explaining the functions of BoFBXs, thereby contributing to the molecular breeding process of cabbage.


Müllerianosis with Intestinal Metaplasia: A Case Report.
Müllerianosis or Müllerian choristomas are developmental alterations that consist of an organoid structure with normal Müllerian tissue. We present a 62-year-old patient diagnosed on ultrasound scanning and on CT scan of bilateral ovarian cysts. During surgery, a left ovarian cyst and retroperitoneal tumor (adhered to sigmoid serous surface) were found. On histological examination, the tumor corresponded with a Müllerian choristoma showing endometrial, endosalpingeal and endocervical epithelium, with foci of intestinal metaplasia, a phenomenon not described in the literature.


Quantifying influences of administrative division adjustment on PM2.5 pollution in China's mega-urban agglomerations.
China's mega-urban agglomerations have experienced severe particulate matter pollution that is accompanied by rapid economic growth and extensive administrative division adjustment (ADA). However, the precise roles of ADA on the environmental quality are unknown. Using the geographical detector and evolution tree model, this study quantifies the effects and mechanisms of ADA on the changes in PM2.5 concentration in three mega-urban agglomerations: Beijing-Tianjin-Hebei (BTH), Yangtze River Delta (YRD), and Pearl River Delta (PRD) during 2000-2017. Our results showed that: (1) ADA had strong positive effects on PM2.5 concentrations in the 0-6 years lag and negative effects in the 7-10 years lag; (2) During 2000-2009, ADA elevated PM2.5 concentration by 5.93% via stimulating the development and transfer of heavy industry and urban sprawl in the BTH; (3) YRD and PRD respectively reduced the ADA's exacerbating effect to 5.26% and 4.98% via reasonable industrial structures and comprehensive cooperation mechanisms; (4) During 2009-2017, BTH and YRD integrated industrial transformation and environmental protection services through ADA, which alleviated 9.51% and 8.49% of PM2.5 pollution. PRD, meanwhile, accomplished orderly population dispersal and urban expansion by combining ADA with urban planning, thus reducing the PM2.5 concentration by 8.01%. We located three agglomerations in the evolution tree, which provide a basis for formulating relevant policies and region-oriented air pollution joint prevention control strategies.


Defatted Microalgae-Mediated Enrichment of n-3 Polyunsaturated Fatty Acids in Chicken Muscle Is Not Affected by Dietary Selenium, Vitamin E, or Corn Oil.
We previously showed enrichments of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) in broiler chicks fed defatted microalgae. The aims of this study were to determine 1) if the enrichments affected meat texture and were enhanced by manipulating dietary corn oil, selenium, and vitamin E concentrations and 2) how the enrichments corroborated with hepatic gene expression involved in biosynthesis and oxidation of EPA and DHA. Day-old hatching Cornish Giant cockerels (n = 216) were divided into 6 groups (6 cages/group and 6 chicks/cage). Chicks were fed 1 of the 6 diets: a control diet containing 4% corn oil, 25 IU vitamin E/kg, and 0.2 mg Se/kg (4CO), 4CO + 10% microalgae (defatted Nannochloropsis oceanica; 4CO+ MA), 4CO+ MA - 2% corn oil (2CO+MA), 2CO+MA + 75 IU vitamin E/kg (2CO+MA+E), 2CO+MA + 0.3 mg Se/kg (2CO+MA+Se), and 2CO+MA+E + 0.3 mg Se/kg (2CO+MA+E+Se). After 6 wk, fatty acid profiles, DHA and EPA biosynthesis and oxidation, gene expression, lipid peroxidation, antioxidant status, and meat texture were measured in liver, muscles, or both. Compared with the control diet, defatted microalgae (4CO+MA) enriched (P < 0.05) DHA and EPA by ≤116 and 24 mg/100 g tissue in the liver and muscles, respectively, and downregulated (41-76%, P < 0.01) hepatic mRNA abundance of 4 cytochrome P450 (CYP) enzymes (CYP2C23b, CYP2D6, CYP3A5, CYP4V2). Supplemental microalgae decreased (50-82%, P < 0.05) lipid peroxidation and improved (16-28%, P < 0.05) antioxidant status in the liver, muscles, or both. However, the microalgae-mediated enrichments in the muscles were not elevated by altering dietary corn oil, vitamin E, or selenium and did not affect meat texture. The microalgae-mediated enrichments of DHA and EPA in the chicken muscles were associated with decreased hepatic gene expression of their oxidation, but were not further enhanced by altering dietary corn oil, vitamin E, or selenium.


A 72-year-old woman with an uncorrected tetralogy of Fallot presenting with possible pulmonary endocarditis: a case report.
Tetralogy of Fallot is one of the most common forms of cyanotic congenital heart disease and in the absence of surgical correction it has an elevated early mortality, with most patients dying in childhood.The authors reported this case because of the unusual course of an uncorrected tetralogy of Fallot. There are only a few reports of patients with an uncorrected tetralogy of Fallot who reach an advanced age and to the best of our knowledge this is the first case report of a possible endocarditis in a patient with an uncorrected tetralogy of Fallot who is older than 70 years. The authors present a case of a 72-year-old Caucasian woman with uncorrected tetralogy of Fallot who was admitted with fever and heart failure to our Cardiology Department with possible infective endocarditis. The longevity of this patient is probably due to the association between a large ventricular septal defect, a balanced subpulmonary stenosis and to the presence of systemic hypertension. After empiric antibiotic therapy, the patient was discharged and no surgical intervention was performed due to her previous benign evolution.


Self-assembled peptide-substance P hydrogels alleviate inflammation and ameliorate the cartilage regeneration in knee osteoarthritis.
Self-assembled peptide (SAP)-substance P (SP) hydrogels can be retained in the joint cavity longer than SP alone, and they can alleviate inflammation and ameliorate cartilage regeneration in knee osteoarthritis (OA). We conducted a preclinical study using diverse animal models of OA and an in vitro study using human synoviocytes and patient-derived synovial fluids to demonstrate the effect of SAP-SP complex on the inflammation and cartilage regeneration. Surgical induction OA model was prepared with New Zealand white female rabbits and chemical induction, and naturally occurring OA models were prepared using Dunkin Hartely female guinea pigs. The SAP-SP complex or control (SAP, SP, or saline) was injected into the joint cavities in each model. We performed micro-computed tomography (Micro-CT) analysis, histological evaluation, immunofluorescent analysis, and terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling (TUNEL) assay and analyzed the recruitment of intrinsic mesenchymal stem cells (MSCs), macrophage activity, and inflammatory cytokine in each OA model. Human synoviocytes were cultured in synovial fluid extracted from human OA knee joints injected with SAP-SP complexes or other controls. Proliferative capacity and inflammatory cytokine levels were analyzed. Alleviation of inflammation, inhibition of apoptosis, and enhancement of intrinsic MSCs have been established in the SAP-SP group in diverse animal models. Furthermore, the inflammatory effects on human samples were examined in synoviocytes and synovial fluid from patients with OA. In this study, we observed that SAP-SP showed anti-inflammatory action in OA conditions and increased cartilage regeneration by recruiting intrinsic MSCs, inhibiting progression of OA. These therapeutic effects have been validated in diverse OA models, including rabbits, Dunkin Hartley guinea pigs, and human synoviocytes. Therefore, we propose that SAP-SP may be an effective injectable therapeutic agent for treating OA. In this manuscript, we report a preclinical study of novel self-assembled peptide (SAP)-substance P (SP) hydrogels with diverse animal models and human synoviocytes and it displays anti-inflammatory effects, apoptosis inhibition, intrinsic mesenchymal stem cells recruitments and cartilage regeneration.


Differential scanning calorimetry differences in micronized and unmicronized nimesulide uptake processes in biomembrane models.
Nimesulide release from micronized and unmicronized drug particles was tested at pH 7.4 by measuring the transfer to dimyristoylphosphatidylcholine liposomes (multilamellar and unilamellar vesicles), chosen as a biomembrane model. The perturbing effect of increasing molar fractions of pure nimesulide on the thermotropic behaviour of dimyristoylphosphatidylcholine liposomes was investigated by differential scanning calorimetry. In order to study the drug dissolution process by its uptake into void liposomes, measurements were carried out on suspensions of blank liposomes added to weighed amounts of free powdered nimesulide (micronized and unmicronized). The amount of drug transferred was quantified by comparing the effect caused by the dissolved and released drug to that caused by the free drug that had been previously molecularly dissolved in the liposomes. The calorimetric results show that the dissolution rate depends on the nimesulide form (micronized or unmicronized), and that the transfer to the void liposomes is quicker when the drug is in a micronized form. The uptake was faster when unilamellar vesicles were used instead of multilamellar vesicles because of the greater lipid surface. The calorimetric technique could represent an alternative 'in vitro' method that can be applied to the study of the dissolution kinetics directly at the site of drug uptake, mimicking a biological system.


Fishway in hydropower dams: a scientometric analysis.
Building dams for hydroelectric use causes several negative effects on the aquatic fauna with special attention to fish communities. In fact, among other impacts, dams act as a barrier for migratory fish, causing discontinuities in rivers and not allowing fish to move to the headwaters to breed and back to the lower portions of rivers, to grow. For more than 300 years, fishways have been used to minimize the impact of dams. Here, we assess the worldwide knowledge about fishways, identifying the temporal and spatial pattern and the situation of Brazil in this global pattern. For this, we conducted scientometric research on the Web of Science repository with the following words: weir, fish, facilities, ladder, pass, dam, fish ladder, fish pass, fishway, hydropower, Petromyzon, and salmon between 1985 and 2019. Initially, we obtained 1282 articles. After a selection, 324 articles aimed to describe fishway efficiency and the relationship with the fish fauna remained. Most of the articles on dams, fishways, and fish are from North America and Europe. Among the articles in South America, most are from Brazil. Nonetheless, information on the topic is incipient in Brazil, since the country has one of the biggest hydropower in the world and 42 scientific articles about fishways published in the international scientific database. Ecology is the area of knowledge with most articles, with continuous growth in the last 10 years. Studies in the field of ecology are strategical, as this field can integrate different areas of knowledge to test the efficiency of fishways in fish conservation and may be able to answer the question: "Are fishways an ecological trap?" Research focusing on this question is important to understand the efficiency of fishways to better evaluate solutions to minimize the negative effects of dams on fish and increase the effectiveness of fishways.


The use of isotopic tracers in studying lipid metabolism in human subjects.
We have attempted to evaluate some of the tracer methodologies involved in studying lipid metabolism in humans. The magnitude of this subject prohibits a comprehensive review of all areas. Since the major function of adipose tissue appears to be to supply the body with energy, we have particularly emphasized the approaches used to study the mobilization and oxidation of fat. The importance of these issues, as well as the increasing availability of non-radioactive tracers, suggest an optimistic future for this area of research.


Retrospective review of thoracoamniotic shunting using a double-basket catheter for fetal chylothorax.
From a single-center retrospective cohort with fetal chylothorax, we evaluated the factors related to the decision to use shunting, poor prognostic factors, and reported shunting outcomes with a new double basket-catheter device. A retrospective single-center study was performed in 35 cases of fetal chylothorax. There were 35 cases of chylothorax: 23 with hydrops and 12 without hydrops. Twenty-one procedures were performed on 15 fetuses (11 with hydrops) with a single shunt in 11, two shunts in 3 and four shunts in 1. All 12 nonhydropic cases survived. In 23 hydropic cases, overall survival rates with and without thoracoamniotic shunting were 46 and 33%, respectively. The mortality rates of fetal hydropic cases with and without ascites were 93 and 11%, respectively. Fetal ascites, progression of fetal hydrops, and premature delivery at <33 weeks were significant risk factors for a poor prognosis. Progression of polyhydramnios after shunting was also associated with a poor prognosis. Obstruction of the catheter was observed in 38%. There were no direct fetal deaths associated with shunting. Thoracoamniotic shunting should be considered for pleural effusion before development of fetal hydrops, or at least before the appearance of fetal ascites. A double-basket catheter tends to be obstructive, but may be less invasive for fetuses.


Dopamine denervation in the functional territories of the striatum: a new MR and atlas-based 123I-FP-CIT SPECT quantification method.
Current quantification methods of 123I-FP-CIT SPECT rely on anatomical parcellation of the striatum. We propose here to implement a new method based on MRI segmentation and functional atlas of the basal ganglia (MR-ATLAS) that could provide a reliable quantification within the sensorimotor, associative, and limbic territories of the striatum. Patients with Parkinson's disease (PD), idiopathic rapid eye movement sleep behavioral disorder (iRBD), and healthy controls underwent 123I-FP-CIT SPECT, MRI, motor, and cognitive assessments. SPECT data were corrected for partial volume effects and registered to a functional atlas of the striatum to allow quantification in every functional region of the striatum (nucleus accumbens, limbic, associative, and sensorimotor parts of the striatum). The MR-ATLAS quantification method is proved to be reliable in every territory of the striatum. In addition, good correlations were found between cognitive dysexecutive tests and the binding within the functional (limbic) territories of the striatum using the MR-ATLAS method, slightly better than correlations found using the anatomical quantification method. This new MR-ATLAS method provides a robust and useful tool for studying the dopaminergic system in PD, particularly with respect to cognitive functions. It may also be relevant to further unravel the relationship between dopaminergic denervation and cognitive or behavioral symptoms.


Probing Medin Monomer Structure and its Amyloid Nucleation Using 13C-Direct Detection NMR in Combination with Structural Bioinformatics.
Aortic medial amyloid is the most prevalent amyloid found to date, but remarkably little is known about it. It is characterised by aberrant deposition of a 5.4 kDa protein called medin within the medial layer of large arteries. Here we employ a combined approach of ab initio protein modelling and 13C-direct detection NMR to generate a model for soluble monomeric medin comprising a stable core of three β-strands and shorter more labile strands at the termini. Molecular dynamics simulations suggested that detachment of the short, C-terminal β-strand from the soluble fold exposes key amyloidogenic regions as a potential site of nucleation enabling dimerisation and subsequent fibril formation. This mechanism resembles models proposed for several other amyloidogenic proteins suggesting that despite variations in sequence and protomer structure these proteins may share a common pathway for amyloid nucleation and subsequent protofibril and fibril formation.


Identification and characterization of a novel phosphoregulatory site on cyclin-dependent kinase 5.
Cyclin-dependent kinase 5 (CDK5) is a serine/threonine kinase essential for embryonic development whose overactivation has been implicated in several pathologies including neurodegeneration, cancer cell metastasis and type II diabetes. Therefore, it is important to investigate molecular mechanism(s) that mediate regulation of CDK5 activity. Here we identify and characterize a novel phosphoregulatory site on CDK5. Our mass spectrometry analysis identified seven putative phosphorylation sites on CDK5. Using phosphomimetic and non-phosphorylatable mutants, we determined that phosphorylation of S47, one of the identified sites, renders the kinase catalytically inactive. The inactivation of the kinase due to the phosphomimetic change at S47 results from inhibition of its interaction with its cognate activator, p35. We connect the effect of this regulatory event to a cellular phenotype by showing that the S47D CDK5 mutant inhibits cell migration and promotes cell proliferation. Together, these results have uncovered a potential physiological mechanism to regulate CDK5 activity. The evolutionary placement of a phosphorylatable residue (S/T) at this position not only in CDK5 but also in the majority of other CDK family members suggests that this phosphosite may represent a shared regulatory mechanism across the CDK family.


Correlations between exposure to deoxynivalenol and zearalenone and the immunohistochemical expression of estrogen receptors in the intestinal epithelium and the mRNA expression of selected colonic enzymes in pre-pubertal gilts.
Plant-based materials used in the production of pig feed are very often contaminated with deoxynivalenol and zearalenone. Daily intake of small amounts of these mycotoxins with feed induces various subclinical states in gilts and influences different biological processes. The aim of this preclinical study was to determine the correlation between monotonic doses of zearalenone and deoxynivalenol (40 μg/kg body weight and 12 μg/kg body weight, respectively, administered over a period of 42 days) and the immunohistochemical expression of estrogen receptors in the intestinal tract and the mRNA expression of selected colonic enzymes. The immunohistochemical expression of estrogen receptor alpha was observed in the colon, but its intensity varied in different weeks of exposure. A minor increase in estrogen receptor beta expression was noted only in the colon, whereas the expression of cytochrome P450 1A1 enzyme mRNA and mRNA isoform of the glutathione S-transferase π gene decreased. The observed correlations suggest that the risk of loss of control over the biotransformation and biological activity of the parent compounds in distal intestinal mucosa is delayed.


HCV-associated thrombocytopenia: clinical characteristics and platelet response after recombinant alpha2b-interferon therapy.
Hepatitis C virus (HCV) has been proposed as a possible causative agent of chronic thrombocytopenia. We investigated HCV infection in a series of 51 unselected Spanish patients with chronic acquired thrombocytopenia. Anti-HCV and HCV viraemia were detected in 13/51 (22.5%) of cases; this prevalence was particularly significant when compared with HCV seropositivity in age-matched controls (0.4%). Anti-HCV-positive patients, four men and nine women with a median age of 59.3 years (range 36-72), had a mean platelet count of 55.8 x 109/l (range 12-96). Only one of our HCV-positive thrombocytopenic patients had hypersplenism. Platelet-associated IgG (PAIgG) was negative, as measured by immunofluorescent flow cytometric analysis in 11/13 HCV-positive thrombocytopenic patients. Thus, thrombocytopenia in our HCV-positive patients appeared to be non-autoimmune mediated. In six patients, a trial of recombinant alpha2b-interferon (IFN-alpha) given at a dose of 3 MU three times per week for 6-24 months gave a durable (> 1 year) and significant increase in platelet count in all six patients. The maximum increase occurred after 6 months of IFN-alpha therapy. In conclusion, the ability of IFN-alpha to increase platelet counts in HCV-positive thrombocytopenic patients supports mechanisms involving a direct role for HCV inhibiting platelet production.


Simultaneous appearance of keratin modifications and gamma-glutamyltransferase activity as indicators of tumor progression in mouse skin papillomas.
gamma-Glutamyltransferase (GGT), an enzyme not found in normal adult epidermis, was detected in most skin papillomas larger than 13 mm in diameter and in all squamous carcinomas induced by 7,12-dimethylbenz[a]anthracene initiation and 12-O-tetradecanoylphorbol 13-acetate promotion in noninbred Sencar mice. Furthermore, these GGT-positive lesions were also characterized by a marked decrease or absence of high-molecular-weight components of epidermal keratin. Since these characteristics are common to both carcinomas and large papillomas but are practically undetectable in normal epidermis and small papillomas, GGT activity and lack of high-molecular-weight keratin components seem to be good indicators of tumor progression, i.e., from papilloma to squamous carcinoma.


TRPM1: a vertebrate TRP channel responsible for retinal ON bipolar function.
The transient receptor potential (TRP) channels affect essential functions widely in sensory systems of various species, both invertebrates and vertebrates. The channel protein encoded by the trp gene, the first identified TRP superfamily molecule, is known to mediate the Drosophila light response. A vertebrate TRP channel playing a crucial role in the visual system has not yet been discovered, although numerous studies have revealed primal functions of TRP superfamily molecules in various sensory systems other than vision. In the retina, which is the entry tissue in the vertebrate visual pathway, the transduction cation channel in ON bipolar cells has been elusive, despite intensive investigation by many researchers over a long period of time. Recent studies finally revealed that TRPM1, the first member of the melanoma-related transient receptor potential (TRPM) subfamily to be discovered, is a visual transduction channel in retinal ON bipolar cells. This review covers the significant discoveries on the physiological function and regulatory mechanism of the TRPM1 channel in retinal ON bipolar cells and the association of human TRPM1 mutations with congenital stationary night blindness.


Extending the novel |ρ|-based phasing algorithm to the solution of anomalous scattering substructures from SAD data of protein crystals.
Owing to the importance of the single-wavelength anomalous diffraction (SAD) technique, the recently developed |ρ|-based phasing algorithm (SM,|ρ|) incorporating the inner-pixel preservation (ipp) procedure [Rius & Torrelles (2021). Acta Cryst A77, 339-347] has been adapted to the determination of anomalous scattering substructures and its applicability tested on a series of 12 representative experimental data sets, mostly retrieved from the Protein Data Bank. To give an idea of the suitability of the data sets, the main indicators measuring their quality are also given. The dominant anomalous scatterers are either SeMet or S atoms, or metals/clusters incorporated by soaking. The resulting SAD-adapted algorithm solves the substructures of the test protein crystals quite efficiently.


Ultrastructural study of morphological changes in Schistosoma mansoni after in vitro exposure to the monoterpene rotundifolone.
Schistosomiasis, a parasitic disease caused by trematode flatworms of the genus Schistosoma, affects more than 200 million people worldwide, and its control is dependent on a single drug, praziquantel. Here, we report the in vitro effect of rotundifolone, a monoterpene isolated from Mentha x villosa (Lamiaceae), on Schistosoma mansoni adult worms. The in vitro effect of rotundifolone on adult Schistosoma mansoni was evaluated by analysis of behavior and mortality and through a scanning electron microscopic analysis of ultrastructural changes in the tegument of the worms. At concentrations of 3.54 and 7.09μg/mL-1 rotundifolone, no worm mortality was observed at any of the sampling intervals. A minor reduction in movement of the tail, suckers, and gynecophoral canal membrane was observed after 96 h of exposure to 7.09μg/mL-1 rotundifolone. At 70.96μg/mL-1, a lack of movement was observed from 72h onwards and all worms were deemed dead; similar effects were observed at 48h with 177.4μg/mL-1, and at 24h with 354.8μg/mL-1 and 700.96μg/mL-1. Rotundifolone also caused death of all parasites and separation of coupled pairs into individual males and females after 24h at 354.8μg/mL-1. The main changes in the tegument induced by the different ROT treatments were: after 24h incubation, bubble lesions spread over the entire body and loss of tubercles occurred in some regions of the ventral region.


Localization of neuroactive substances in the vertebrate retina: evidence for lamination in the inner plexiform layer.
The inner plexiform layer (IPL) of the vertebrate retina is a multilaminated region containing bipolar, amacrine, interplexiform and ganglion cell processes. Immunohistochemical methods clearly demonstrate the existence of various neuroactive substances in distinct morphological types of amacrine cells. Sufficient detail in the staining consistently delineates processes containing these neuroactive substances in multiple laminae of the IPL. Thus, the histochemical approach provides a powerful tool for the analysis of the laminar organization of the IPL and can also be used to further clarify the functional role of various transmitter and peptide substances in the retina.


Work engagement scale: Validating the Japanese UWES-9 standard through an automotive industry sample.
The Utrecht Work Engagement Scale (UWES) is widely used as a psychometric assessment scale to measure work engagement by relative evaluation. Determining standard values for absolute evaluation would make it more useful. The merit of absolute evaluation is that it can offer an objective evaluation to personnel members regardless of their status in the organization. This study examines the criteria for absolute evaluation of the Japanese version of UWES-9 and creates a database for the evaluation of work engagement. To examine the evaluation criteria for the total points of UWES-9 for 417 automotive industry workers, responses were validated via a one-way analysis of variance and receiver-operating characteristic analysis, using the scales of "worthwhileness of work" and "level of job satisfaction" in the Brief Job Stress Questionnaire with similar work engagement concepts. In both scales, the ability to predict was at its highest when divided into the high work engagement group (wherein the total points of UWES-9 are 21 points and above). In the relative evaluation, 24 points from the average of the total points of UWES-9 is the standard. In the absolute evaluation, the lower standard around 21 points is probable.


Empiric antifungal and outcome in ICU patients.
The management of invasive candidiasis (IC) remains a major challenge in intensive care units (ICU). On the one hand, it becomes admitted that delayed antifungal is an independent mortality factor. In the other hand, the unreasonable administration of antifungal agents is implicated in emergence of resistant Candida strains. Aim: to evaluate whether empirical antifungal therapy (EAFT) improves survival at day 28 and prevents a new episode of candidemia in septic patients without proven Candida infection. a 8-years retrospective double cohort, monocentric study, comparing two arms of ICU non neutropenic septic patients without proven fungal infection according to administration or not of an EAFT. The primary outcome was the 28-day mortality and the second was the occurrence of candidemia. The analysis was adjusted on Acute Physiology And Chronic Health Evaluation II (APACHE II) score, Candida score, invasive ventilation and central catheterisation. 247 patients were included (EAFT group, n=125 and non EAFT group, n=122). No improvement of 28-day survival was found. These results were in accordance both in crude analysis and after adjusting on factors mentioned above. No preventing effect on a new episode of candidemia. Nevertheless, a beneficial effect of EAFT on survival was found in patients with an APACHE II score<16: OR=0.68; CI 95% [0.53-0.87]; p=0.002. no beneficial impact of an EAFT on 28- day survival neither in preventing the occurrence of candidemia in non neutropenic septic critically patients. In patients with APACHE II score less than 16, there was a beneficial effect on survival.


The effect of diazepam pretreatment on the succinylcholine-induced rise in intraocular pressure.
The influence of diazepam on some adverse effects of succinylcholine was studied double-blind. Thirty patients (ASA I-II) were allocated to groups receiving either diazepam 0.08 mg/kg or d-tubocurarine 0.05 mg/kg 5 min before a bolus of succinylcholine, 1 mg/kg and 1.5 mg/kg, respectively. Fasciculations were more frequent in the diazepam group (80%) than in the d-tubocurarine group (13%). Relaxation, onset and duration of neuromuscular blockade were comparable in the two groups. The rise in intraocular pressure after succinylcholine and endotracheal intubation was small (0.27 kPa = 2 mmHg) but significant (P less than 0.01) after diazepam pretreatment. In this group the rise in intraocular pressure was 50% lower than the rise seen in the d-tubocurarine group (P less than 0.01). We conclude that pretreatment with diazepam 0.08 mg/kg will reduce but not prevent a rise in the intraocular pressure after succinylcholine in a rapid sequence induction. In the management of patients with penetrating eye injuries the use of succinylcholine still carries some risk even after diazepam pretreatment.


Rod-coating: towards large-area fabrication of uniform reduced graphene oxide films for flexible touch screens.
A novel strategy is developed for the large-scale fabrication of reduced graphene oxide films directly on flexible substrates in a controlled manner by the combination of a rod-coating technique and room-temperature reduction of graphene oxide. The as-prepared films display excellent uniformity, good transparency and conductivity, and great flexibility in a touch screen.


Ossifying malignant Leydig (interstitial) cell tumour of the testis.
An ossifying malignant Leydig cell tumour of the testis in a patient with associated gynaecomastia is presented. The criteria for diagnosing malignancy in these tumours are briefly discussed.


Malonyl-coenzyme A reductase from Chloroflexus aurantiacus, a key enzyme of the 3-hydroxypropionate cycle for autotrophic CO(2) fixation.
The 3-hydroxypropionate cycle is a new autotrophic CO(2) fixation pathway in Chloroflexus aurantiacus and some archaebacteria. The initial step is acetyl-coenzyme A (CoA) carboxylation to malonyl-CoA by acetyl-CoA carboxylase, followed by NADPH-dependent reduction of malonyl-CoA to 3-hydroxypropionate. This reduction step was studied in Chloroflexus aurantiacus. A new enzyme was purified, malonyl-CoA reductase, which catalyzed the two-step reduction malonyl-CoA + NADPH + H(+) --> malonate semialdehyde + NADP(+) + CoA and malonate semialdehyde + NADPH + H(+) --> 3-hydroxypropionate + NADP(+). The bifunctional enzyme (aldehyde dehydrogenase and alcohol dehydrogenase) had a native molecular mass of 300 kDa and consisted of a single large subunit of 145 kDa, suggesting an alpha(2) composition. The N-terminal amino acid sequence was determined, and the incomplete gene was identified in the genome database. Obviously, the enzyme consists of an N-terminal short-chain alcohol dehydrogenase domain and a C-terminal aldehyde dehydrogenase domain. No indication of the presence of a prosthetic group was obtained; Mg(2+) and Fe(2+) stimulated and EDTA inhibited activity. The enzyme was highly specific for its substrates, with apparent K(m) values of 30 microM malonyl-CoA and 25 microM NADPH and a turnover number of 25 s(-1) subunit(-1). The specific activity in autotrophically grown cells was 0.08 micromol of malonyl-CoA reduced min(-1) (mg of protein)(-1), compared to 0.03 micromol min(-1) (mg of protein)(-1) in heterotrophically grown cells, indicating downregulation under heterotrophic conditions. Malonyl-CoA reductase is not required in any other known pathway and therefore can be taken as a characteristic enzyme of the 3-hydroxypropionate cycle. Furthermore, the enzyme may be useful for production of 3-hydroxypropionate and for a coupled spectrophotometric assay for activity screening of acetyl-CoA carboxylase, a target enzyme of potent herbicides.


Interpreting the effect of increasing COD loading rates on the performance of a pre-anoxic MBBR system: implications on the attached and suspended biomass dynamics and nitrification-denitrification activity.
A pre-anoxic MBBR system was subjected to increasing organic loading rates up to 18 gCOD/(m(2) day). At 3 gCOD/(m(2) day), most of the incoming organic matter was removed via denitrification. However, at higher loads, anoxic COD removal became limited by the nitrite/nitrate supply from the aerobic reactor, which assumed an important role in this conversion. Despite the application of low dissolved oxygen (DO) levels (<2 mg/L) in this tank, nitrification was observed to be nearly complete until 8 gCOD/(m(2) day). As the organic input was increased, the maximum specific nitrifying activity gradually declined. Activity tests suggested that an oxygen-limited environment was established in the biofilm. At lower loads [3-8 gCOD/(m(2) day)], the nitrification product obtained was affected by the DO concentration, whereas from 16 to 21 gCOD/(m(2) day), nitrite/nitrate profiles were likely associated with microbial stratification in the biofilm. The results also indicated that the role of the suspended biomass in the overall nitrification and denitrification can be very significant in high loaded MBBRs and should not be neglected, even at low HRTs.


GENETIC ASSOCIATION BETWEEN ARTERIAL STIFFNESS-RELATED GENE POLYMORPHISMS IN BRVO AND CRVO PATIENTS IN A TURKISH POPULATION.
To investigate possible associations between five different single-nucleotide polymorphisms, from genes associated with arterial stiffness and branch retinal vein occlusion (BRVO), or central retinal vein occlusion. A total of 187 patients with retinal vein occlusion (133 with BRVO and 54 with central retinal vein occlusion), and 167 controls, were enrolled in this study. All subjects were screened for hypertension, diabetes, smoking status, body mass index, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, total cholesterol, and very low-density lipoprotein. The genotyping of adiponectin +276 G/T, ACE I/D, AGTR1 A1166C, eNOS E298D, and p22phox -242 C/T polymorphisms was performed using real-time polymerase chain reaction. The percentage of the adiponectin +275 T allele carriers was significantly higher in the BRVO patients (37%) than in the controls (23%, P < 0.001). Similarly, the percentage of AGTR1 1166 C allele carriers was significantly higher in the BRVO patients (38%) than in the controls (24%, P < 0.001). At the multiple logistic regression analysis, the adiponectin +275 T allele carrier and AGTR1 1166 C allele carrier status were found to be associated with an increased risk of BRVO (TT vs. GG and TG: odds ratio = 2.278, P = 0.002, 95% confidence interval: 1.370-3.789; CC vs. AA and AC: odds ratio = 1.804, P = 0.025, 95% confidence interval: 1.079-3.017). The genotype distributions or allelic frequencies of ACE I/D, eNOS E298D, and p22phox -242 C/T did not significantly differ between the patients with BRVO and the control subjects. There was no significant difference between the central retinal vein occlusion patients and controls for the genotype or the allele frequency distributions of all evaluated single-nucleotide polymorphisms. Adiponectin +276 G/T and AGTR1 A1166C single-nucleotide polymorphism are likely to be risk factors for BRVO.


A mechanism underlying NOTCH-induced and ubiquitin-mediated JAK3 degradation.
Although NOTCH signaling is well known to regulate lymphopoiesis, Janus kinase 3 (JAK3) also plays a critical role in promoting lymphocyte development. We have previously found that NOTCH signaling leads to the degradation of JAK3 in B lineage cells, suggesting that NOTCH signaling exerts its biological effect on lymphopoiesis through modulating JAK3 levels. Here, we delineate the biochemical mechanisms involved in NOTCH-induced JAK3 ubiquitination and degradation. NOTCH signaling is known to transcriptionally activate the genes encoding ASB2 (ankyrin-repeat SOCS box containing protein 2) and SKP2 (S-phase kinase-associated protein 2). We show that not only NOTCH but also ASB2 and SKP2 can promote the ubiquitination and degradation of JAK3. Both ASB2 and SKP2 can interact with JAK3 through different domains; the FERM and pseudo-kinase domains each had high affinities for ASB2, whereas the kinase domain primarily associated with SKP2. ASB2 and SKP2 previously have been shown to associate with each other to bridge the formation of a non-canonical Cullin1 and Cullin5-containing dimeric E3 ligase complex. Interestingly, the R980W mutant of JAK3 exhibited diminished interaction with SKP2 and resistance to NOTCH or ASB2-induced degradation. Furthermore, dominant-negative mutants of either Cullin1 or Cullin5, which lack the C terminus responsible for recruiting the E2 enzymes, were able to prevent JAK3 degradation induced by both ASB2/SKP2 and NOTCH signaling. Together, these results suggest that JAK3 ubiquitination involves the non-canonical dimeric E3 ligase complex, and the R980W mutant will serve as an excellent tool for investigating the biological significance of NOTCH-mediated JAK3 turnover.


Characterization of Sodium Channel Mutations in the Dengue Vector Mosquitoes Aedes aegypti and Aedes albopictus within the Context of Ongoing Wolbachia Releases in Kuala Lumpur, Malaysia.
Specific sodium channel gene mutations confer target site resistance to pyrethroid insecticides in mosquitoes and other insects. In Aedes mosquito species, multiple mutations that contribute to resistance vary in their importance around the world. Here, we characterize voltage sensitive sodium channel (Vssc) mutations in populations of Aedesaegypti from Kuala Lumpur, Malaysia, and look at their persistence in populations affected by ongoing Wolbachia releases (a dengue control measure). We also describe a Vssc mutation in Aedesalbopictus (F1534L) found for the first time in Malaysia. We show that there are three predominant Vssc haplotypes in Aedesaegypti in this region, which all persist with regular backcrossing, thereby maintaining the original genetic composition of the populations. We identify changes in genotype frequency in closed populations of Ae. aegypti maintained for multiple generations in laboratory culture, suggesting different fitness costs associated with the genotypes, some of which may be associated with the sex of the mosquito. Following population replacement of Ae. aegypti by Wolbachia in the target area, however, we find that the Vssc mutations have persisted at pre-release levels. Mosquitoes in two genotype classes demonstrate a type I pyrethroid resistance advantage over wildtype mosquitoes when exposed to 0.25% permethrin. This resistance advantage is even more pronounced with a type II pyrethroid, deltamethrin (0.03%). The results point to the importance of these mutations in pyrethroid resistance in mosquito populations and the need for regular backcrossing with male mosquitoes from the field to maintain similarity of genetic background and population integrity during Wolbachia releases.


Gate-tunable spin waves in antiferromagnetic atomic bilayers.
Remarkable properties of two-dimensional (2D) layer magnetic materials, which include spin filtering in magnetic tunnel junctions and the gate control of magnetic states, were demonstrated recently1-12. Whereas these studies focused on static properties, dynamic magnetic properties, such as excitation and control of spin waves, remain elusive. Here we investigate spin-wave dynamics in antiferromagnetic CrI3 bilayers using an ultrafast optical pump/magneto-optical Kerr probe technique. Monolayer WSe2 with a strong excitonic resonance was introduced on CrI3 to enhance the optical excitation of spin waves. We identified subterahertz magnetic resonances under an in-plane magnetic field, from which the anisotropy and interlayer exchange fields were determined. We further showed tuning of the antiferromagnetic resonances by tens of gigahertz through electrostatic gating. Our results shed light on magnetic excitations and spin dynamics in 2D magnetic materials, and demonstrate their potential for applications in ultrafast data storage and processing.


A contribution to understanding the morphology of the genus Anthroherpon (= Parantrophilon syn. nov.) and new combination for a species from the Balkan Peninsula (Insecta, Coleoptera, Leiodidae, Cholevinae, Leptodirini).
The subterranean beetle genus Anthroherpon Reitter, 1889 stands for an iconic cave-adapted organism due to wide range of the morphological variability and the diversification of its species in the Central and Southern Dinarides. The monotypical genus Parantrophilon Noesske, 1914 is nested within the distribution area of Anthroherpon and it is also narrowly distributed. After a morphological study and comparison with the related material of the genus Anthroherpon Reitter, 1889, the synonymy of Parantrophilon to Anthroherpon is established. Aredescription of the genus Anthroherpon Reitter, 1889 is given.


Selective inhibition of protein synthesis by hypertonic medium in Marituba (Bunyaviridae) virus-infected L-A9 cells.
Elevation of the NaCl concentration in the growth medium of L-A9 cells caused an inhibition of the protein synthesis accompanied by a complete breakdown of polyribosomes. However, a complete recovery of the rate of protein synthesis was observed when isotonicity was restored. In Marituba virus infected cells, protein synthesis became resistant to hypertonic treatment. Under hypertonic conditions cellular protein synthesis was selectively suppressed and an enhancement of virus proteins was observed. Analysis of the virus specific proteins by polyacrylamide gel electrophoresis revealed that the synthesis of G1 was unalterable, and N was stimulated.


Coronary heart disease morbidity and mortality in hypercholesterolemic men predicted from an exercise test: the Lipid Research Clinics Coronary Primary Prevention Trial.
A positive exercise electrocardiogram (ECG) has been proved to predict cardiovascular events in asymptomatic normolipidemic men. To study whether it is also predictive for hypercholesterolemic men, data from 3,806 asymptomatic hypercholesterolemic men in the Lipid Research Clinics Coronary Primary Prevention Trial were analyzed. All the men had performed a submaximal treadmill exercise test at baseline, before they were assigned to the cholestyramine or placebo treatment group. Because of missing or inconclusive data, 31 men were excluded from the analyses. A test was positive if the ST segment was displaced by greater than or equal to 1 mm (visual code) or there was greater than or equal to 10 microV-s change in the ST integral (computer code), or both. The prevalence of a positive test was 8.3%. During the 7 to 10 year (mean 7.4) follow-up period, the mortality rate from coronary heart disease was 6.7% (21 of 315) in men with a positive test and 1.3% (46 of 3,460) in men with a negative test (placebo and cholestyramine groups combined). The age-adjusted rate ratio for a positive test, compared with a negative test, was 6.7 in the placebo group and 4.8 in the cholestyramine group. With use of Cox's proportional hazards models, it was found that the risk of death from coronary heart disease associated with a positive test was 5.7 times higher in the placebo group and 4.9 times higher in the cholestyramine group after adjustment for age, smoking history, systolic blood pressure, high density lipoprotein cholesterol and low density lipoprotein cholesterol. A positive test was not significantly associated with nonfatal myocardial infarction.(ABSTRACT TRUNCATED AT 250 WORDS)


Beneficial effect of polyherbal formulation in letrozole induced Polycystic ovarian syndrome (PCOS).
PCOS is an endocrine condition that results in enlarged ovaries with tiny cysts on the margins. The present study aims to investigate the beneficial effect of polyherbal formulation in Letrozole induced PCOS in female Albino Wistar rats. Acute toxicity study of the polyherbal formulation by administering a single dose (2000 mg/kg) was done in female Albino Wistar rats (20 weeks, 250 g) following OECD guideline 423. For PCOS induced study female Albino Wistar rats were divided into six groups (6 animals/group). Group I (control) was given 0.5% carboxymethylcellulose (CMC) suspension daily as vehicle control. Letrozole (1 mg/kg) was orally administered for 21 days in Group II to VI for induction of PCOS. After induction of PCOS, animals were treated with standard drug (Group III- Clomiphene citrate- 1 mg/kg) and polyherbal tablets (Group IV - 500 mg/kg, Group V- 750 mg/kg, and Group VI - 1000 mg/kg) up to 50 days. Vaginal smears were taken daily to check the estrous cycle. Body weight was measured weekly. Blood samples were withdrawn on 0,21 and 50 days for the determination of fasting blood glucose, lipid profile, LH, FSH, and hormonal levels. Administration of letrozole caused the abnormality in serum sex hormone profile, lipid profile, glucose, and the estrous cycle. The treatment with polyherbal formulation significantly decreased (P < 0.0001) the level of testosterone and improved estradiol and progesterone levels (P < 0.0001). There was a decrease in elevated glucose levels from 71.51 ± 0.15 mg/dl in disease induced group to 57.33 ± 1.90 mg/dl in treatment groups. The triglycerides level was normalized to 33.41 ± 1.81 mg/dl and HDL level was increased to 40.63 ± 1.35 mg/dl in treatment groups. The polyherbal formulation by exerting its beneficial effect also caused the disappearance of the cysts in the ovaries. The polyherbal formulation was found to be effective in PCOS. The effect may be attributed to the individual herbs reported having a significant effect on the pathophysiology of letrozole induced PCOS.


Effect of post-exercise protein-leucine feeding on neutrophil function, immunomodulatory plasma metabolites and cortisol during a 6-day block of intense cycling.
Whey protein and leucine ingestion following exercise increases muscle protein synthesis and could influence neutrophil function during recovery from prolonged intense exercise. We examined the effects of whey protein and leucine ingestion post-exercise on neutrophil function and immunomodulators during a period of intense cycling. In a randomized double-blind crossover, 12 male cyclists ingested protein/leucine/carbohydrate/fat (LEUPRO 20/7.5/89/22 g h(-1), respectively) or isocaloric carbohydrate/fat control (CON 119/22 g h(-1)) beverages for 1-3 h post-exercise during 6 days of high-intensity training. Blood was taken pre- and post-exercise on days 1, 2, 4 and 6 for phorbol myristate acetate (PMA)-stimulated neutrophil superoxide (O2 (-)) production, immune cell counts, amino acid and lipid metabolism via metabolomics, hormones (cortisol, testosterone) and cytokines (interleukin-6, interleukin-10). During recovery on day 1, LEUPRO ingestion increased mean concentrations of plasma amino acids (glycine, arginine, glutamine, leucine) and myristic acid metabolites (acylcarnitines C14, myristoylcarnitine; and C14:1-OH, hydroxymyristoleylcarnitine) with neutrophil priming capacity, and reduced neutrophil O2 production (15-17 mmol O2 (-) cell(-1) ± 90 % confidence limits 20 mmol O2 (-) cell(-1)). On day 2, LEUPRO increased pre-exercise plasma volume (6.6 ± 3.8 %) but haematological effects were trivial. LEUPRO supplementation did not substantially alter neutrophil elastase, testosterone, or cytokine concentrations. By day 6, however, LEUPRO reduced pre-exercise cortisol 21 % (±15 %) and acylcarnitine C16 (palmitoylcarnitine) during exercise, and increased post-exercise neutrophil O2 (-) (33 ± 20 mmol O2 (-) cell(-1)), relative to control. Altered plasma amino acid and acylcarnitine concentrations with protein-leucine feeding might partly explain the acute post-exercise reduction in neutrophil function and increased exercise-stimulated neutrophil oxidative burst on day 6, which could impact neutrophil-dependent processes during recovery from intense training.


Natural history of Hymenoptera venom allergy in children not treated with immunotherapy.
Differences in treatment approach still exist for children after systemic sting reactions. In addition, there are still some doubts about when systemic reactors should be treated with venom immunotherapy (VIT). To determine the rate of sting recurrence and natural history of Hymenoptera venom allergy (HVA) in children not treated with VIT. A total of 219 children diagnosed as having HVA who were not treated with VIT were identified in 3 pediatric allergology centers. Survey by telephone or mail with the use of a standardized questionnaire was conducted. The number of field re-stings, subsequent symptoms, and provided treatment were analyzed. A total of 130 of the 219 patients responded to the survey, for a response rate of 59.4%. During the median follow-up period of 72 months (interquartile range, 52-85 months), 44 children (77% boys) were stung 62 times. Normal reactions were most common, occurring in 27 patients (62%). Severe systemic reactions (SSRs) occurred in 8 (18%) of those who were re-stung. The subsequent reaction was significantly milder (P < 0.001), especially in the case of patients re-stung by the same insect (P < .001). None of the children with prediagnostic large local reactions and negative test results for venom specific IgE developed SSRs after re-sting by the culprit insect (P = .03). In children with SSRs, median time from diagnosis to re-sting was 2 times longer than that in those with large local reactions and normal reactions (P = .007). Most children with HVA not treated with VIT reported milder reactions after a re-sting. Probability of SSR to re-sting increases along with the severity of initial reaction.


An acidic phospholipase A₂ with antibacterial activity from Porthidium nasutum snake venom.
Snake venoms are complex mixtures of proteins among which both basic and acidic phospholipases A(2) (PLA(2)s) can be found. Basic PLA(2)s are usually responsible for major toxic effects induced by snake venoms, while acidic PLA(2)s tend to have a lower toxicity. A novel PLA(2), here named PnPLA(2), was purified from the venom of Porthidium nasutum by means of RP-HPLC on a C18 column. PnPLA(2) is an acidic protein with a pI of 4.6, which migrates as a single band under both non-reducing and reducing conditions in SDS-PAGE. PnPLA(2) had a molecular mass of 15,802.6 Da, determined by ESI-MS. Three tryptic peptides of this protein were characterized by HPLC-nESI-MS/MS, and N-terminal sequencing by direct Edman degradation showing homology to other acidic PLA(2)s from viperid venoms. PnPLA(2) displayed indirect hemolytic activity in agarose erythrocyte-egg yolk gels and bactericidal activity against Staphylococcus aureus in a dose-dependent manner, with a MIC and MBC of 32 μg/mL. In addition, PnPLA(2) showed a potent inhibitory effect on platelet aggregation with doses up to 40 μg/mL. This acidic PLA(2), in contrast to basic enzymes isolated from other viperid snake venoms, was not cytotoxic to murine skeletal muscle myoblasts C(2)C(12). This is the first report on a bactericidal protein of Porthidium nasutum venom.


Can drip irrigation under mulch be replaced with shallow-buried drip irrigation in spring maize production systems in semiarid areas of northern China?
In recent years, shallow-buried drip irrigation in spring maize production has gradually replaced drip irrigation under plastic films and has become a common irrigation method in semiarid areas of northern China. Two years of field experiments were carried out in the semiarid area of western Jilin province to compare the two drip irrigation methods in the spring maize production system. The treatments included MW1 (drip irrigation under mulch + moderate irrigation amount), MW2 (drip irrigation under mulch + high irrigation amount), SM1 (shallow-buried drip irrigation + moderate irrigation amount), and SM2 (shallow-buried drip irrigation + high irrigation amount). The maize yields were significantly higher under mulch than under shallow-buried drip irrigation, but there was no interaction between mulch and the irrigation amount. Drip irrigation under mulch greatly improved spring maize N, P and K uptake compared with that under shallow-buried drip irrigation. The agronomic-use efficiency, recovery-use efficiency, and partial factor productivity were ranked in the order of MW2 > MW1 > SW2 > SW1. The water-use efficiency of drip irrigation under mulch was 7.44% and 6.82% higher than that of shallow-buried drip irrigation under the moderate and high irrigation levels, respectively. However, considering the costs of the plastic mulch, there was no significant (P < 0.05) difference in economic benefits between the SW and MW treatments. Drip irrigation under plastic film provides greater advantages for production, but shallow-buried drip irrigation may be a suitable method for farmers until fertigation technology is further optimized and the problem of plastic film pollution is solved. © 2020 Society of Chemical Industry.


Hammerhead ribozyme design and application.
The emerging knowledge about RNA-based enzymes has already had great impact on our concept of evolutionary history, making the 'RNA world' more likely. It may well have an equally important impact on the diagnostic and therapeutic practices of human and veterinary medicine in the next decade. We are not quite there yet. This review addresses the design and application of hammerhead ribozymes, two aspects of a conserved and most commonly studied and used enzymatically active entity among the RNA enzymes. The emerging picture is one of great diversity. There is at this stage no general cell model nor a clearly preferable ribozyme structure. Each and every cell line (and tissue) may be unique in that they vary with respect to structural requirements for optimal uptake, activity and stability of ribozymes. We may have seen only the tip of the iceberg when it comes to RNA-based enzymes and their roles in biology and medicine.


Characterization of proline endopeptidase from skeletal muscle.
Proline endopeptidase was purified from human muscle by anion-exchange chromatography, thiol-affinity chromatography and chromatography on hydroxyapatite. The enzyme gave a single band on polyacrylamide gel electrophoresis. Activity was maximum at pH 7.0-7.5. The molecular weight (by gel filtration) was 69,000. The enzyme hydrolysed benzyloxycarbonyl-Gly-Pro-7-amido-4-methylcoumarin with Km 32 microM. It was inhibited by di-isopropyl phosphofluoridate and 4-hydroxymercuriphenyl sulphate. Bacitracin inhibited at higher concentrations but lower concentrations stimulated the activity. The enzyme activity appeared largely in the soluble fraction following fractionation of rat muscles. Proline endopeptidase activity in rat muscle was unaltered by treatment of the animals with compound 48/80, a mast cell degranulator.


Research Note: A novel peptide-based ELISA for efficient detection of antibody against chicken infectious anemia virus.
Chicken infectious anemia virus (CIAV) is the pathogen of chicken infectious anemia. Currently, due to the lack of effective diagnostics technology and prevention approach, CIAV has spread globally and caused huge economic losses to poultry industry. In this study, a novel peptide-based ELISA (pELISA) for efficient detection of antibody against CIAV was developed. The peptide (25CRLRRRYKFRHRRRQRYRRRAF45) used in pELISA was highly conserved in VP1 protein of different CIAV isolates. The specificity and reproducibility showed that the pELISA only reacted with sera against CIAV, not with sera against other pathogens tested, and the CV of the intra-/inter-assay of the pELISA was 6.8 to 9.22%. Moreover, the comparison assay using 56 clinical samples showed that the positive rate of the pELISA and the commercial ELISA kit (IDEXX) was 85.7 and 80.4%, respectively. The pELISA generated here provides a rapid and efficient serological detection method for diagnosis of CIAV infection and evaluation of the efficacy of CIAV vaccination.


Effect of a Combined Bleaching Regimen on the Microhardness of a Sealed Methacrylate-based and a Silorane-based Composite.
The use of tooth bleaching agents has been very popular treatment in dentistry. The bleaching agents have an inherent potential to impair surface properties of existing composite resin restorations. This study evaluated the effect of a combined bleaching regimen on the surface microhardness of a Silorane-based and a sealed methacrylate-based composite. Forty-five specimens of methacrylate-based composite (Ice) and 18 specimens of Silorane composite (Filtek Silorane, 3M ESPE; USA) were prepared and randomly divided into 5 (1-5) and 2 (6-7) groups (n=9), respectively. After 8-week aging, groups 1 and 6 were remained with no treatment. In groups 2, 4 and 5, the specimens were covered by a surface sealant and light cured. In groups 3, 4, 5 and 7, the specimens were bleached with hydrogen peroxide 40% and then carbamide peroxide 20% for seven days. In group 5, after bleaching, the sealant was removed by polishing. Surface microhardness was measured and the data were analyzed using one-way ANOVA and Tukey tests (α=0.05). The microhardness values of groups 2 to 4 were significantly lower than that of group1 (p <0.05). There was no significant difference among groups 1, 5, 6 and 7 (p> 0.05). The combined bleaching regimen used in this study had a substantial negative effect on methacrylate and sealed methacrylate composites but not on Silorane composite. Polishing following the bleaching on the sealed composite yielded a hardness value similar to that of unsealed methacrylate composite (control).


AARC Clinical Practice Guideline: Management of Adult Patients With Oxygen in the Acute Care Setting.
Providing supplemental oxygen to hospitalized adults is a frequent practice and can be administered via a variety of devices. Oxygen therapy has evolved over the years, and clinicians should follow evidence-based practices to provide maximum benefit and avoid harm. This systematic review and subsequent clinical practice guidelines were developed to answer questions about oxygenation targets, monitoring, early initiation of high-flow oxygen (HFO), benefits of HFO compared to conventional oxygen therapy, and humidification of supplemental oxygen. Using a modification of the RAND/UCLA Appropriateness Method, 7 recommendations were developed to guide the delivery of supplemental oxygen to hospitalized adults: (1) aim for [Formula: see text] range of 94-98% for most hospitalized patients (88-92% for those with COPD), (2) the same [Formula: see text] range of 94-98% for critically ill patients, (3) promote early initiation of HFO, (4) consider HFO to avoid escalation to noninvasive ventilation, (5) consider HFO immediately postextubation to avoid re-intubation, (6) either HFO or conventional oxygen therapy may be used with patients who are immunocompromised, and (7) consider humidification for supplemental oxygen when flows > 4 L/min are used.


Spruce Budworm (Lepidoptera: Tortricidae) Oral Secretions I: Biology and Function.
The potential roles of the oral secretions (OS) of spruce budworm (SBW; Choristoneura fumiferana Clemens) larvae and factors that may affect the volume of OS disgorged were investigated in the laboratory. Experiments revealed that diet-fed SBW larvae readily disgorge OS when induced ("milked"), with minimal overall cost to their development and eventual pupal weight. Exposure of conspecific larvae to OS throughout larval development negatively affected survival and male pupal weight; however, male development time was faster when exposed to OS. Female pupal weight and development time were not affected. Preliminary experiments suggested that OS had a repellent effect on a co-occurring herbivore, the false hemlock looper, Nepytia canosaria (Walker). OS produced by larvae that fed on three host tree species and on artificial diet significantly increased the grooming time of ants (Camponotus sp.), indicating that SBW OS have an anti-predator function. The volume of OS is significantly greater in L6 than in L4 or L5, with the volume produced by L6 depending on weight and age as well as feeding history at time of milking. These findings indicate that SBW OS function as both an intra- and interspecific epideictic pheromone and as an anti-predator defensive mechanism, while incurring minimal metabolic costs.


Genetic Differentiation among Livestock Breeds-Values for Fst.
(1) Background: The Fst statistic is widely used to characterize between-breed relationships. Fst = 0.1 has frequently been taken as indicating genetic distinctiveness between breeds. This study investigates whether this is justified. (2) Methods: A database was created of 35,080 breed pairs and their corresponding Fst values, deduced from microsatellite and SNP studies covering cattle, sheep, goats, pigs, horses, and chickens. Overall, 6560 (19%) of breed pairs were between breeds located in the same country, 7395 (21%) between breeds of different countries within the same region, 20,563 (59%) between breeds located far apart, and 562 (1%) between a breed and the supposed wild ancestor of the species. (3) Results: General values for between-breed Fst were as follows, cattle: microsatellite 0.06-0.12, SNP 0.08-0.15; sheep: microsatellite 0.06-0.10, SNP 0.06-0.17; horses: microsatellite 0.04-0.11, SNP 0.08-0.12; goats: microsatellite 0.04-0.14, SNP 0.08-0.16; pigs: microsatellite 0.06-0.27, SNP 0.15-0.22; chickens: microsatellite 0.05-0.28, SNP 0.08-0.26. (4) Conclusions: (1) Large amounts of Fst data are available for a substantial proportion of the world's livestock breeds, (2) the value for between-breed Fst of 0.1 is not appropriate owing to its considerable variability, and (3) accumulated Fst data may have value for interdisciplinary research.


Increased serum concentration of ceramides in obese children with nonalcoholic fatty liver disease.
Hepatic lipid accumulation is closely related to the development of insulin resistance, which is regarded as one of the most significant risk factors of nonalcoholic fatty liver disease (NAFLD). Although the exact molecular pathway leading to impaired insulin signaling has not been definitively established, ceramides are suspected mediators of lipid induced hepatic insulin resistance. Therefore, the aim of the study was to evaluate the serum ceramides concentration in obese children with NAFLD. The prospective study included 80 obese children (aged 7-17 years, median 12 years) admitted to our Department to diagnose initially suspected liver disease. Patients with viral hepatitis (HCV, HBV, CMV), autoimmune (AIH), toxic and metabolic (Wilson's disease, alfa-1-antitrypsin deficiency) liver diseases and celiac disease were excluded. NAFLD was diagnosed based on pediatric diagnostic criteria in obese children with liver steatosis in ultrasound (US) as well as elevated alanine transaminase (ALT) serum activity after exclusion of other major liver diseases listed before. Ultrasonography was used as a screening method and for qualitative assessment of the steatosis degree (graded according to Saverymuttu scale). Advanced steatosis was defined as a score > 1. The total intrahepatic lipid content (TILC) was assessed by magnetic resonance proton spectroscopy (1HMRS) which is the most accurate technique for assessment of ectopic fat accumulation. Fasting serum concentration of ceramides was measured in 62 children. NAFLD was diagnosed in 31 children. Significant, positive correlation was found between total serum concentration of ceramides and insulin (r = 0.3, p = 0.02) and HOMA-IR (r = 0.28, p = 0.03). Total ceramide concentration as well as specific fatty acid-ceramides (FA-ceramides) concentrations, namely: myristic, palmitic, palmitoleic, stearic, oleic, behenic and lignoceric were significantly higher (p = 0.004, p = 0.003, p = 0.007, p < 0.001, p = 0.035, p = 0.008, p = 0.003, p = 0.006, respectively) in children with NAFLD compared to controls (n = 14). Moreover, children with NAFLD had significantly higher activity of ALT (p < 0.001) and GGT (p < 0.001), HOMA-IR (p = 0.04), BMI (p = 0.046), waist circumference (p = 0.01) steatosis grade in ultrasound (p < 0.001) and TILC in 1HMRS (p < 0.001) compared to children without NAFLD. We did not find significant differences in total and FA-ceramide species concentrations between children with mild (grade 1) and advanced liver steatosis in ultrasonography (grade 2-3). Elevated ceramide concentrations in obese patients together with their significant correlation with insulin resistance parameters suggest their association with molecular pathways involved in insulin signaling impairment known to be strongly linked to pathogenesis of non-alcoholic fatty liver disease.


Clipping Test of a Radiculomedullary Artery During Resection of a Dorsal Spinal Meningioma.
Arterial supply of the spinal cord is derived from the anterior spinal artery (ASA) and 2 posterior spinal arteries. In the thoracic spine, a few segmental arteries give origins to radiculomedullary arteries (RMAs) that supply the ASA and posterior spinal arteries.1 In the lower thoracic spine, the supply is provided by the Adamkiewicz artery. Spinal meningiomas may be embedded and/or supplied by the RMA, which may be sacrificed to obtain complete resection. Safety of the thoracic RMA occlusion is controversial,2 especially if the Adamkiewicz artery is involved.3 Somatosensory evoked potentials (SSEPs) and motor evoked potentials (MEP) are proposed to detect spinal cord ischemia.4 The RMA supplies the anterior spinal cord, and MEPs seem to be more sensitive than SSEPs to test RMA occlusion.2 SSEP and MEP monitoring during temporary occlusion has been described and significantly changes at 2 and 7 minutes of occlusion.5-8 Safe occlusion with unchanged MEPs after 10-minute temporary occlusion of 32 segmental arteries was reported by Salame et al.9 We intraoperatively discovered an anterior T10 RMA supplying the adjacent meningioma (Video 1). We temporary clipped the artery for 8 minutes. MEPs were recorded before clipping and every 2 minutes. No changes were observed, and the artery was sacrificed. RMA or segmental artery ligature may be required and is frequently performed in deformity, oncologic, and vascular spine surgery. The clipping test with MEP monitoring is a useful and simple intraoperative tool to identify the critical afferents of the ASA. It doesn't require planification or supplementary materials. Further study might be performed to validate the technique.


Re-admissions after ileostomy formation: a retrospective analysis from a New Zealand tertiary centre.
Ileostomy formation is a commonly performed procedure in colorectal surgery. The morbidity associated with ileostomies is substantial, particularly for unplanned hospital re-admissions and re-admissions with dehydration. Studies of post-ileostomy re-admissions from an Australasian institution are currently lacking. This retrospective study aimed to quantify the 60-day re-admission rate after ileostomy formation in a New Zealand tertiary centre and to determine the predictive factors. The surgical database of Auckland City Hospital was searched for all patients aged ≥18 years with a new ileostomy formed between first January 2015 and first January 2019. Patient electronic medical records were reviewed to obtain data regarding the primary outcome of re-admissions within 60 days of discharge, as well as patient and operative variables. Multivariate regression analysis was performed to identify independent predictors of all-cause re-admissions and re-admissions with dehydration. A total of 246 patients with 266 ileostomy formations were included. The 60-day re-admission rate was 29.3%, with dehydration present in 27.0% of these re-admissions. Renal impairment at discharge (odds ratio 2.819, 95% confidence interval 1.087-7.310) and the presence of at least one Clavien-Dindo 1 complication (odds ratio 2.268, 95% confidence interval 1.301-3.954) were independently associated with all-cause re-admission. The independent predictors of re-admission with dehydration were renal impairment at discharge, codeine prescribed on discharge, Charlson Comorbidity Index and body mass index. Unplanned hospital re-admission following ileostomy formation is a significant issue in the New Zealand patient population. Some patient groups are at particularly high risk, such as those with renal impairment at discharge.


Prevention of bacterial adhesion to denture acrylic.
A range of non-toxic polysaccharides were screened for their ability to prevent bacterial adhesion to denture acrylic in vitro. Sodium alginate, karaya gum and carrageenan were found to be the most effective, reducing adhesion of Streptococcus salivarius by 98.7, 97.9 and 99.2 per cent respectively. These three polysaccharides were then tested for their ability to reduce the number of bacteria adhering to dentures in vivo. Sodium alginate was the most effective, reducing the attachment of bacteria to the palate-contacting surface of the denture after 5 h of normal wear by 84 per cent compared with uncoated controls. The results of this investigation suggest that the accumulation of denture plaque may be prevented by frequent application of a renewable, sacrificial coating of a non-toxic polysaccharide.


In vitro activity of sulbactam plus ampicillin against hospital isolates of coagulase-negative staphylococci and Acinetobacter species.
The antimicrobial susceptibility of 54 recent clinical isolates of coagulase-negative slime- and non-slime-producing staphylococci and 52 Acinetobacter spp. to sulbactam, ampicillin and the combination of both drugs with a 1:1 ratio was studied by means of an agar dilution test. The coagulase-negative staphylococci showed resistance against sulbactam alone, whereas ampicillin as a single agent was nearly as active as sulbactam plus ampicillin (mode of MIC and MBC 0.03 and 4 mg/l vs. 1 mg/l; geometric mean of MIC and MBC 0.38 and 0.56 vs. 0.26 and 0.38 mg/l, respectively). Among slime-producing or non-slime-producing strains, there was no difference in the susceptibility against ampicillin alone compared to the sulbactam/ampicillin combination, with the exception of the higher MBC (mode: 4 mg/l) for slime-producing strains. Both ampicillin and the sulbactam/ampicillin combination were more active against non-slime-producing than slime-producing strains with modes of MIC and MBC of 0.03 vs. 1 or 4 mg/l. Acinetobacter spp. were susceptible to sulbactam alone (mode of MIC and MBC 1 mg/l; geometric mean of MIC and MBC 1.51 and 2.98, respectively), but resistant to ampicillin. However, the sulbactam/ampicillin combination was highly active against Acinetobacter spp. (mode of MIC and MBC 0.5 and 2 mg/l; geometric mean of MIC and MBC 0.74 and 2.08 mg/l, respectively).


Determinants of left ventricular function improvement for cardiac resynchronization therapy candidates.
A waiting period of more than 3 months is recommended for patients before undergoing cardiac resynchronization therapy (CRT). However, due to an anticipated high mortality rate, early implementation of CRT might be beneficial for some patients. We aimed to evaluate the rate and the probability of left ventricular (LV) function improvement and their predictors in patients with heart failure (HF) with indications for CRT. From March 2011 to February 2014, a total of 5625 hospitalized patients for acute HF were consecutively enrolled in 10 tertiary hospitals. Among them, we analysed 1792 patients (mean age 63.96 ± 15.42 years, female 63.1%) with left ventricular ejection fraction (LVEF) ≤ 35% at the baseline echocardiography and divided them into three groups: 144 with left bundle branch block (LBBB), 136 with wide QRS complexes without LBBB, and 1512 not having these findings (control). We compared and analysed these three groups for improvement of LV function at follow-up echocardiography. In patients who met CRT indications (patients with LBBB or wide QRS complexes without LBBB), logistic regression was performed to identify risk factors for no improvement of LV. No improvement of LV was defined as LVEF ≤ 35% at follow-up echocardiography or the composite adverse outcomes: death, heart transplantation, extracorporeal membrane oxygenation, or use of a ventricular assist device before follow-up echocardiography. A classification tree was established using the binary recursive partitioning method to predict the outcome of patients who met CRT indications. In a median follow-up of 11 months, LVEF improvement was observed in 24.3%, 15.4%, and 40.5% of patients with LBBB, wide QRS complexes without LBBB, and control, respectively. Patients meeting CRT indications had higher 3 month mortality rates than the control (24.6% vs. 17.7%, P = 0.002). Multivariable logistic regression analysis revealed that large LV end-systolic dimension [odds ratio (OR) 1.10, 95% confidence interval (CI) 1.05-1.15, P < 0.001], low LVEF (OR 0.92, 95% CI 0.87-0.98, P = 0.006), diabetes requiring insulin (OR 6.49, 95% CI 2.53-19.33, P < 0.001), and suboptimal medical therapy (OR 6.85, 95% CI 3.21-15.87, P < 0.001) were significant factors predictive of no improvement. A decision tree analysis was consistent with these results. Patients with CRT indications had higher mortality during their follow-up compared with control. LV function improvement was rare in this population, especially when they had some risk factors. These results suggest that the uniform waiting period before CRT implantation could be reconsidered and individualized.


Predictive risk factors for complicated pneumonia in Malaysian children.
To investigate baseline characteristics associated with complicated community-acquired pneumonia (CAPc) in Malaysian children. CAPc, such as pleural effusion and/or empyema, is on the rise, especially in Southeast Asian children, and the reasons for this are unknown. A retrospective study was conducted on all children aged 2-16 years who were admitted to the University Malaya Medical Centre with community-acquired pneumonia between 2012 and 2014. In this study, of the 343 children, 58 (17%) developed CAPc. Chinese ethnicity (P < 0.001), reduced breastfeeding duration (P = 0.003), not receiving outpatient antibiotic (P < 0.001) and exposure to parental smoking (P < 0.001) were identified as risk factors for CAPc. Markedly increased respiratory rate (P = 0.021) and thrombocytosis (P < 0.001) were noted as the clinical parameters for CAPc. This study identifies some modifiable risk to reduce the burden of pneumonia complications.


Correction to: Hand dexterity, not handgrip strength, is associated with executive function in Japanese community-dwelling older adults: a cross-sectional study.
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Bone marrow cells are a rich source of growth factors and cytokines: implications for cell therapy trials after myocardial infarction.
Results from clinical trials suggest that cardiac function after acute myocardial infarction (AMI) can be enhanced by an intracoronary infusion of autologous unselected nucleated bone marrow cells (BMCs). Release of paracrine factors has been proposed as a mechanism for these therapeutic effects; however, this hypothesis has not been tested in humans. BMCs and peripheral blood leucocytes (PBLs) were obtained from 15 patients with AMI and cultured in serum-free medium to obtain conditioned supernatants (SN). BMC-SN stimulated human coronary artery endothelial cell proliferation, migration, and tube formation, and induced cell sprouting in a mouse aortic ring assay. Moreover, BMC-SN protected rat cardiomyocytes from cell death induced by simulated ischaemia or ischaemia followed by reperfusion. While PBL-SN promoted similar effects on endothelial cells and cardiomyocytes, BMC-SN and PBL-SN in combination promoted synergistic effects. As shown by ProteinChip and GeneChip array analyses (each performed in triplicate), BMCs and PBLs expressed distinct patterns of pro-angiogenic and cytoprotective secreted factors. Our data support the paracrine hypothesis and suggest that characterization of the BMC secretome may lead to an identification of factors with therapeutic potential after AMI.


Synergistic interaction between prostaglandins and PAF-acether in experimental animals and man.
Platelet activating factor (PAF-acether) is released from a variety of inflammatory cell types and has properties appropriate to a mediator of allergy and inflammation. Here, we have examined the interaction between PAF-acether and the prostaglandins, PGE2 and ZK 36374 (a stable analogue of prostacyclin, PGI2) in the skin of guinea-pigs and human volunteers. PGE2 and ZK 36374 significantly potentiated increased plasma protein extravasation induced by PAF-acether in guinea-pigs, assessed by extravasation of I-125-HSA. In addition, PGE2 significantly potentiated the ability of PAF-acether to elicit acute wheal (volume) and flare responses in human skin. The inflammatory properties of PAF-acether should not be considered in isolation since this phospholipid interacts synergistically with prostaglandins which are recognised as modulators of inflammation.


Gametocytogenesis and ribosomal rRNA gene organisation in the rodent malarias Plasmodium chabaudi and Plasmodium berghei.
A cloned Plasmodium berghei (ANKA) isolate was syringe passaged repeatedly to generate a line that was non-infective to Anopheles stephensi. Ribosomal gene organisation of this non-infective line was then compared to its infective ancestor. DNA was also prepared from asexual parasites and gametocytes of P. chabaudi and the arrangement of the rRNA genes of this species was studied. Although macrogametocytes have many more ribosomes than microgametocytes, this increase does not appear to stem from an amplification of the rRNA genes, as no differences either in the quantity or the arrangement of the rDNA could be detected. Furthermore, the loss of infectivity of the P. berghei gametocytes does not seem to be due to a reduction or rearrangement of sequences coding for the rRNA genes. P. chabaudi and P. berghei DNA failed to show any homology to a repetitive DNA sequence cloned from P. falciparum. We conclude that this probe, PFH8rep20, is specific for P. falciparum.


The role of estrogen deprivation therapy in premenopausal women with primary unresectable intracardiac leiomyomatosis: a systematic review and meta-analysis.
Intracardiac leiomyomatosis (ICLM) is a rare life-threatening form of intravenous leiomyomatosis (IVLM). The incomplete resection and recurrence are associated with high morbidity and mortality. The objective of this study is to identify that whether estrogen deprivation therapies, including bilateral salpingo-oophorectomy (BSO)-based surgery and gonadotrophin releasing hormone agonists (GnRHa) administration, could bring benefits to patients with primary unresectable ICLM. PubMed/MEDLINE (Ovid) was searched (up to May 2021) for studies reporting individual patient data on demographics, clinicopathological features, treatment, and follow-up information. Exclusion criteria were patients who may have been included in two or more publications. This study was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A total of 114 patients from 70 papers were included. Several reports showed that the tumor in the right atrium and inferior vena cava shrank dramatically after BSO-based surgery, or GnRHa administrated preoperatively in premenopausal women. The rate of complete resection was 64.04% in patients with ICLM, which was 85.25% in no/slight adhesion and no pulmonary nodules group, while 22.22% in firm/extensive adhesion and/or pulmonary nodules group (p < 0.0001). Meanwhile, the recurrence rates in patients with complete resection and incomplete resection were 4.29% and 37.84% respectively (p < 0.0001). Furthermore, complete resection with BSO had the lowest recurrence rate of 3.13%, incomplete resection with BSO had a progression rate of 45.45%, while incomplete resection with ovarian preservation had the highest progression rate of 75.00%. The recurrence rate of ICLM was closely related to firm/extensive adhesion in IVC or above, and/or pulmonary nodules. BSO-based surgery might reduce the recurrence rate no matter ICLM could be completely resected or not. In addition, estrogen deprivation therapies could decrease tumor burden as a primary treatment, and further make a secondary complete resection feasible in premenopausal women with initially unresectable ICLM.


Malignant schwannoma presenting as a skin mass. Confirmation by the demonstration of myelin basic protein within tumor cells.
A malignant spindle cell tumor with features of a malignant schwannoma presented as a skin mass in the neck of a 13-year-old child. The histologic diagnosis was supported by the demonstration of myelin basic protein within the atypical cells using a monoclonal antibody to myelin basic protein and an unlabelled antibody peroxidase-antiperoxidase technique.


Evidence for conformational changes in Escherichia coli porphobilinogen deaminase during stepwise pyrrole chain elongation monitored by increased reactivity of cysteine-134 to alkylation by N-ethylmaleimide.
Porphobilinogen deaminase from Escherichia coli becomes progressively more susceptible to inactivation by the thiophilic reagent N-ethylmaleimide (NEM) as the catalytic cycle proceeds through the enzyme-intermediate complexes ES, ES2, ES3, and ES4. Site-directed mutagenesis of potentially reactive cysteines has been used to identify cysteine-134 as the key residue that becomes modified by the reagent and leads to inactivation. Since cysteine-134 is buried at the interface between domains 2 and 3 of the E. coli deaminase molecule, the observations suggest that a stepwise conformational change occurs between these domains during each stage of tetrapyrrole assembly. Interestingly, mutation of the invariant active-site cysteine-242 to serine leads to an enzyme with up to a third of the catalytic activity found in the wild-type enzyme. Electrospray mass spectrometry indicates that serine can substitute for cysteine as the dipyrromethane cofactor attachment site.


A review on the treatment of intimal hyperplasia with perivascular medical devices: role of mechanical factors and drug release kinetics.
Intimal hyperplasia (IH) is a significant factor limiting the success of revascularization surgery for blood flow restoration. IH results from a foreign body response and mechanical disparity that involves complex biochemical reactions resulting in graft failure. The available treatment option utilizes either different pharmacological interventions or mechanical support to the vascular grafts with limited success. This review explains the pathophysiology of IH, responsible mechanical and biological factors, and treatment options, emphasizing perivascular devices. They are designed to provide mechanical support and pharmacology actions. The perivascular drug delivery concept has successfully demonstrated efficacy in various animal studies. Accurate projections of drug release mechanisms using mathematical modeling could be used to formulate prolonged drug elution devices. Numerical modeling aspects for the prediction of design outcomes have been given due importance that fulfills the unmet clinical need for better patient care. IH could be effectively prevented by simultaneous mechanical scaffolding and sustained local drug delivery. Future perivascular medical devices could be designed to integrate these essential features. Numerical modeling for device performance prediction should be utilized in the development of next-generation perivascular devices.


Chloride and water distribution in human red cells.
1. The influence of the pH and the temperature on the cellular chloride and water content was investigated in human red cells, the cellular KC1 concentrations of which varied between 10 and 600 mM. The compositions of the media (10-600 mM-KC1, 1 mM-NaC1, 27 mM sucrose) at each single KC1 concentration were constant at the different values of the pH and the temperature. 2. The variation of the cellular KC1 concentration was obtained by washing the cells with KC1 salt solutions containing nystatin...


[Perimortal management--humanistic assignment and responsibility. Attempt at status determination].
The scientific research and practical use of all questions concerning life demands interdisciplinary cooperation. This is the result of neglection of death and dying and new social and medical developments as there are institutionalisation of dying and scientific-technical progress. The foundation of the working group "perimortal medicine" in 1983 in the Association for clinical medicine gives the possibility to discuss theoretical and practical questions concerning the end of life, death and dying. It seems to be important, that also bereavement and sympathy belongs to the topics. The results will help to develop the quality of care for the dying and the survivors.