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The impulse oscillation system (IOS) has been developed recently to measure respiratory system resistance (Rrs) and reactance (Xrs) at different frequencies up to > or = 25 Hz. IOS has, however, not been validated against established techniques. This study compared IOS with the classical pseudorandom noise forced oscillation technique (FOT) and body plethysmographic airway resistance (Raw) in 49 subjects with a variety of lung disorders and a wide range of Raw (0.10-1.28 kPa x L(-1) x s). Rrs,IOS was slightly greater than Rrs,FOT, especially at lower frequencies, with a mean +/- SD difference at 5-6 Hz of 0.14 +/- 0.09 kPa x L(-1) x s. Comparisons with the wave-tube technique applied on two analogues indicated an overestimation by IOS. Xrs,IOS and Xrs,FOT were very similar, with a slightly higher resonant frequency with IOS than with FOT (mean difference +/- SD 1.35 +/- 3.40 Hz). Raw was only moderately correlated with Rrn,FOT and Rrs-IOS; although the mean differences were small (0.04 +/- 0.14 kPa x L(-1)s for Rrs6,FOT and -0.10 +/- 0.14 kPa x L(-1) x s for Rrs5,IOS), IOS and FOT markedly underestimated high resistance values. In conclusion, the impulse oscillation system yields respiratory system resistance and reactance values similar, but not identical to those provided by the forced oscillation technique. | Plethysmography, Whole Body |
The National Comprehensive Cancer Network, an NPO organization comprised of university hospitals and cancer centers in the US. The publication of clinical practice guidelines on the treatment, diagnosis, prevention and screening is one of important activities. Background factors of prostate cancer patients, such as the prevalence, age at the diagnosis and mortality are markedly different between Western countries and Asia. Thus, various factors should be taken into consideration at the treatment choice for individual patients. Experts from Asian countries were published as the Asia Consensus Statement. In this review, we explain important points of the Asia Consensus Statement such as differences in the epidemiological backgrounds of patients, differences in treatment options and differences in medical insurance systems. | Prostatic Neoplasms |
Investigations into the possibility of using the chilled adult release system are continuing as an alternative method to the release of sterile tsetse flies, Glossina pallidipes Austen (Diptera: Glossinidae) in cardboard boxes. Exposing tsetse flies to 4 degrees C for 6 h caused negligible mortality. A combination of chilling and irradiation resulted in reduced quantities of seminal contents being transferred to females. Mortality of flies after bulk irradiation was lower when a thermos flask was used than expanded polystyrene. Mortality after removal from cold storage increased with age. Flies that did not have a blood meal for 3 d prior to exposure to cold had a lower overnight survival than flies that were deprived of a blood meal for 1 or 2 d. Exposure of adult male tsetse flies to low temperature should be for as short a duration as is practical, so that the fitness of the released sterile flies is not unduly compromised. It is also necessary to ensure that losses are minimized during bulk irradiation of adult flies. It would be desirable to have minimal losses after the combined effects of irradiation, cold, and transportation, such that a sufficient number of sterile male flies will still be available to successfully compete for mating opportunities with wild females. | Tsetse Flies |
Solanum lycocarpum (Solanaceae), a Brazilian medicinal plant known as wolf fruit," contains about 1.5% of glycoalkaloids in its dried fruits, consisting mainly of solamargine and solasonine. The present work reports the obtainment of the alkaloidic extract of the S. lycocarpum fruit by acid-base extraction and the isolation of the major alkaloid heterosides by chromatographic means, as well as the evaluation of their in vitro schistosomicidal activities. The in vitro schistosomicidal activities of the alkaloidic extract of S. lycocarpum fruits and its isolated steroidal alkaloids were undertaken against adult worms of Schistosoma mansoni. The alkaloidic extract (20, 32, and 50 mug mL(-1)), solasonine (50 muM), solamargine (32 and 50 muM), and equimolar mixture of glycoalkaloids (20, 32, and 50 muM) lead to the separation of all couple worms and extensive disruption on their teguments, such as sloughing, as well as their deaths within 24 h of incubation. In addition, the alkaloidic extract (10 and 15 mug mL(-1)), solasonine (50 muM), solamargine (10, 15, and 20 muM), and equimolar mixtures of glycoalkaloids (10 and 15 muM) reduced the development of eggs produced by the adult worms. Solamargine, containing the sugar chain moiety chacotriose, was more active than the solasonine, which contains solatriose sugar chain moiety. A synergistic effect was also observed for a mixture of solamargine and solasonine. Therefore, the alkaloidic extract of S. lycocarpum, and its major components, solamargine and solasonine, showed promising schistosomicidal activity." | Solanaceous Alkaloids |
The locus coeruleus (LC) is the largest catecholaminergic nucleus and extensively projects to widespread areas of the brain and spinal cord. The LC is the largest source of noradrenaline in the brain. To date, the only examined Delphinidae species for the LC has been a bottlenose dolphin (Tursiops truncatus). In our experimental series including different Delphinidae species, the LC was composed of five subdivisions: A6d, A6v, A7, A5, and A4. The examined animals had the A4 subdivision, which had not been previously described in the only Delphinidae in which this nucleus was investigated. Moreover, the neurons had a large amount of neuromelanin in the interior of their perikarya, making this nucleus highly similar to that of humans and non-human primates. This report also presents the first description of neuromelanin in the cetaceans' LC complex, as well as in the cetaceans' brain. | Locus Coeruleus |
The epitope structure of human alpha-fetoprotein (AFP) was studied using more than 50 monoclonal antibodies (MAB) to human AFP. These MAB obtained from various world laboratories of the TD-2 AFP Workshops of the International Society for Oncodevelopmental Biology and Medicine (ISOBM-1996-1998-2000) were analyzed by competitive immunoaffinity electrochromatography (IAE) on nitrocellulose membranes (NCM). Five types of interaction of the AFP-MAB complex with the MAB fixed on NCM were found: 1) complete neutralization; 2) partial neutralization; 3) unidirectional neutralization; 4) enhanced binding; 5) lack of interaction. By IAE, 51 MAB were found to recognize 23 different epitopes in the AFP molecule. Based on these findings, an epitope map of AFP was designed which consists of eight epitope clusters and eight individual epitopes. The epitope location is considered with respect to the conformational state of the AFP molecule. Possible causes of the five types of interaction found on neutralization are discussed. | Fetal Globulins |
We present a two-dimensional gel electrophoretic method which affords a diagnostic means for the identification of the neuron-specific clathrin assembly protein AP180 in crude cytosolic and microsomal fractions of bovine brain. The method is based on the finding that in the presence of sodium dodecyl sulfate (SDS) in a newly developed continuous high salt Tris-acetate-EDTA buffer system protein AP180 migrates at a rate corresponding to its molecular weight of approximately 120,000, while in other more commonly used SDS-polyacrylamide gel electrophoresis methods it behaves anomalously as a 170- to 180-kDa polypeptide. By combining electrophoresis in the Tris-acetate-EDTA system in the first dimension with either the electrophoretic system of Laemmli [Laemmli, U.K. (1970) Nature (London) 227, 680-685] or that of Neville [Neville, D.M. (1971) J. Biol. Chem. 246, 6328-6334] in the second dimension, it is possible to identify AP180 in complex protein mixtures, because it is the only major protein that fell significantly off a diagonal defined by other proteins. A comparison of the microsomal and soluble fractions examined in this manner reveals that most of the AP180 is present in the soluble fraction." | Monomeric Clathrin Assembly Proteins |
Following the recent discovery of Bourbon virus (BRBV) as a human pathogen, and the isolation of the virus from Amblyomma americanum (L.) collected near the location of a fatal human case, we undertook a series of experiments to assess the laboratory vector competence of this tick species for BRBV. Larval ticks were infected using an immersion technique, and transstadial transmission of virus to the nymphal and then to the adult stages was demonstrated. Transstadially infected nymphs transmitted virus to adult ticks at very high rates during cofeeding, indicating the presence of infectious virus in the saliva of engorging ticks. Vertical transmission by transstadially infected females to their progeny occurred, but at a low rate. Rabbits fed on by infected ticks of all active life stages developed high titers of antibody to the virus, demonstrating host exposure to BRBV antigens/live virus during tick blood feeding. These results demonstrate that A. americanum is a competent vector of BRBV and indicate that cofeeding could be critical for enzootic maintenance. | Thogotovirus |
Axillary-femoral bypass is sometimes performed for complex aortoiliac occlusive disease in patients unfit for aortic surgery or in those with aortic infection. Typically, older patients with medical comorbidities that commonly accompany atherosclerotic or aneurysmal disease are involved and can tolerate the theoretic risk of limited flow volume associated with long, small diameter, axillary-femoral grafts. However, a subset of younger, healthier, more vigorous patients outside the typical atherosclerotic or aneurysmal demographic occasionally come to axillary-femoral bypass and may experience symptoms of distal hypoperfusion if flow volumes cannot meet demand. We present a series of patients with primary aortic infection treated with aortic ligation and axillary-femoral bypass, who then progressed to symptoms of visceral, spinal, or extremity ischemia from inadequate distal perfusion. | Axillofemoral Bypass Grafting |
To prevent serious complications and facilitate efficient and effective management of patients admitted to the emergency department or intensive care settings, it is extremely important to differentiate, quickly, between elevated concentrations of alcohol in the blood and compromised neurological status due to brain injury or other pathology. This research analyzed the relationship between blood alcohol concentrations (BACs) estimated from venous blood samples and those estimated from breath samples that were obtained using the Alco-Sensor III device with an attached tube for passive nasal breath sampling. Blood and breath samples, as well as brief medical histories and demographic and environmental data, were obtained and recorded for 35 adult trauma patients admitted to two major urban emergency departments. Passively expired nasal breath provided an excellent estimate of BAC measured from venous blood (range, 0 to 0.32) as evidenced in the extremely high regression coefficient (r = 0.99; slope = 1.22; p less than 0.0001). BAC assessment and monitoring, through the application of passive nasal breath sampling, provides a means of rapidly estimating BAC, and thus can facilitate diagnosis and the initiation of appropriate management and treatment. | Breath Tests |
OBJECTIVES: Accurate management of metabolic decompensation in maple syrup urine disease (MSUD) has a crucial role, as acute attacks can cause neurological sequels and can be life threatening. Here, we aimed to evaluate effect of sodium phenylbutyrate (NaPBA) in acute management of MSUD attacks. METHODS: Episodes with an initial plasma leucine (Leu) level above 750 micromoL/L and that require hospitalization due to clinical findings of Leu neurotoxicity and/or feeding difficulties were included to the study. Patients who had no molecular diagnosis and a regular follow-up were excluded. Clinical findings, laboratory results and therapy responses were reviewed, retrospectively. RESULTS: Ten patients who experienced 19 distinct episodes of MSUD attacks were enrolled. Initial median Leu level was 901.67 (range 756-1989.11) and 33.9 micromoL/L (range 7.91-347.3 micromoL/L) at the end of therapy. None of our patients underwent extracorporeal toxin removal during the course of attack. In patients with serial plasma quantitative amino acid sampling, mean Leu reduction rate was calculated to be 529.68 +/- 250.08 micromoL/L/day at the 24th h of treatment and 318.72 +/- 191.52 micromoL/L/day at the 48th h of treatment. CONCLUSIONS: This study is the first original study that investigates the effect of NaPBA in management of acute attacks of MSUD patients from Turkey. We suggest that NaPBA treatment in MSUD attacks can ameliorate clinical and biochemical findings. This therapeutic option should be considered especially in smaller centers without the toxin removal chance and for patients who were not appropriate for extracorporeal toxin removal like hemodynamic instability. | Maple Syrup Urine Disease |
The high-fertility Meishan pig is currently categorized into medium sized (MMS) and small sized (SMS) based on body size. To identify causal genes responsible for the variation in body size within the two categories, we sequenced individuals representing the entire consanguinity of the existing Meishan pig. This enabled us to conduct genome selective signal analysis. Our findings revealed the genomes of MMS and SMS are stratified, with selective sweep regions formed by differential genomic intervals between the two categories enriched in multiple pig body size related quantitative trait loci (QTLs). Furthermore, the missense mutation c.575T > C of candidate causal gene NR6A1, accounting for the variation in lumbar vertebrae number in pigs, was positively selected in MMS only, leading to an increase in body length of MMS at 6 months of age. To precisely identify causal genes accounting for body size variation through multi-omics, we collected femoral cartilage and liver transcription data from MMS and SMS respectively, and re-sequencing data from pig breeds exhibiting varying body sizes. We found that two selected regions where the RSAD2-CMPK2 and COL3A1 genes are located, respectively, showed different haplotypes in pig breeds of varying body size, and was associated with body or carcass length in hybridized Suhuai pig. Additionally, the above three hub genes, were significantly greater expressed in SMS femoral cartilage and liver tissues compared to MMS. These three genes could strengthen the pathways related to bone resorption and metabolism in SMS, potentially hindering bone and skeletal development and resulting in a smaller body size in SMS. These findings provide valuable insights into the genetic mechanism of body size variation in Meishan pig population. | Viperin Protein |
Active plant metabolites (APM) are recognized as modifiers of ruminal microbial fermentation including methanogenesis and biohydrogenation of fatty acids (FA). Coleus amboinicus Lour. leaves (CAL) are rich in several APM, which could serve as ruminal fermentation modulators. A phytochemical analysis showed that CAL contain phenolic acids (10.4 mg.g-1 dry matter [DM]; high in rosmarinic acid), flavonoids (2.6 mg.g-1 DM), diterpenes (2 mg.g-1 DM), and linolenic acid (35.4 g (100 g)-1 FA). This study aimed to investigate the effect of CAL on ruminal methanogenesis and biohydrogenation as well as basic fermentation characteristics and microbial populations. The in vitro experiment was carried out using Hohenheim gas test system with 40 mL of buffered ruminal fluid incubated for 24 h at 39 degrees C in anaerobic conditions. Approximately 400 mg (DM basis) of total mixed ration (TMR) was used as a control substrate and the CAL substrate was used at doses of 10, 20, 40, and 80 mg DM replacing equal amounts of TMR. Addition of CAL decreased methane production up to 30% linearly as the amount of CAL increased (P < 0.05). In vitro dry matter digestibility and ammonia tended to increase with increasing doses of CAL. Concentration of total volatile fatty acids was not affected by the CAL although there appeared to be a minor positive linear trend; however, acetate, butyrate, and isobutyrate proportion increased quadratically (P < 0.001). CAL tended to linearly increase alpha-linolenic acid and conjugated linoleic acid as well as increased stearic acid concentration in buffered ruminal fluid. CAL particularly increased total protozoa and bacterial populations during fermentation, but inhibited methanogens. It is concluded that the CAL may be promising to be used as a feed additive to decrease methanogenesis as well as biohydrogenation of FA in the rumen. | Coleus |
The immunocompromised host is at an increased risk for pulmonary and extrapulmonary NTM infections. Where data are available in these specific populations, increased mortality is observed with NTM disease. Prior to starting therapy for NTM disease, providers should ensure diagnostic criteria are met as treatment is long and often associated with significant side effects and toxicities. Treatment should involve 2 to 4 agents and be guided by cultures and antimicrobial susceptibilities. Drug interactions are important to consider, especially in those with HIV or transplant recipients. Whenever possible, immunosuppression should be reduced or changed." | Mycobacterium Infections, Nontuberculous |
OBJECTIVES: The purpose of this review is to examine the plausibility of a causal relationship between maternity ward practices and lactation success. METHODS: Studies were located with MEDLINE, from our personal files, and by contacting researchers working in this field. Of the 65 studies originally reviewed, 18 met our inclusion criteria (i.e., hospital-based intervention, experimental design with randomization procedures, or quasi-experimental design with adequate documentation). RESULTS: Meta-analysis indicated that commercial discharge packs had an adverse effect on lactation performance. The impact of early mother-infant contact on lactation success was unclear. Rooming-in and breast-feeding guidance in a rooming-in context had a beneficial impact on breast-feeding among primiparae. Breast-feeding on demand was positively associated with lactation success. In-hospital formula supplementation of 48 mL per day was not associated with poor breast-feeding performance. CONCLUSIONS: Hospital-based breast-feeding interventions can have a beneficial effect on lactation success, particularly among primiparous women. | Nurseries, Hospital |
The plague agent Yersinia pestis persists for years in the soil. Two millennia after swiping over Europe and North Africa, plague established permanent foci in North Africa but not in neighboring Europe. Mapping human plague foci reported in North Africa for 70 years indicated a significant location at <3 kilometers from the Mediterranean seashore or the edge of salted lakes named chotts. In Algeria, culturing 352 environmental specimens naturally containing 0.5 to 70 g/L NaCl yielded one Y. pestis Orientalis biotype isolate in a 40 g/L NaCl chott soil specimen. Core genome SNP analysis placed this isolate within the Y. pestis branch 1, Orientalis biovar. Culturing Y. pestis in broth steadily enriched in NaCl indicated survival up to 150 g/L NaCl as L-form variants exhibiting a distinctive matrix assisted laser desorption-ionization time-of-flight mass spectrometry peptide profile. Further transcriptomic analyses found the upregulation of several outer-membrane proteins including TolC efflux pump and OmpF porin implied in osmotic pressure regulation. Salt tolerance of Y. pestis L-form may play a role in the maintenance of natural plague foci in North Africa and beyond, as these geographical correlations could be extended to 31 plague foci in the northern hemisphere (from 15 degrees N to 50 degrees N). | Yersinia pestis |
Chemoselective ligation of carbohydrates and polypeptides was achieved using an adipic acid dihydrazide cross-linker. The reducing end of a carbohydrate is efficiently attached to peptides in two steps, constructing a glycoconjugate in high yield and with high regioselectivity, enabling the production of homogeneous glycoconjugates. | Glycopeptides |
This study aimed to characterize the structural and physico-mechanical properties of bacterial cellulose (BC) produced by Gluconoacetobacter xylinus TJU-S8 which was isolated from Chinese persimmon vinegar. Thermogravimetric analysis (TGA) showed that BC exhibited a good thermal stability. Solid-state nuclear magnetic resonance (NMR), fourier transform infrared spectroscopy (FT-IR) and x-ray diffraction (XRD) analysis revealed that BC had a typical crystalline form of the cellulose I. The BC membrane had typical characteristics such as nanodimensional network and microfibrils obtained by scanning electron microscopy (SEM). Moreover, the bacterial cellulose chitosan (BC-C) membrane and bacterial cellulose carboxymethyl chitosan (BC-CC) membrane were synthesized which showed significant inhibition against the growth of both Escherichia coli and Staphylococcus aureus. These results indicated superior properties of BC that advocated its effectiveness for various applications. | Gluconacetobacter xylinus |
OBJECTIVE: To assess the effect of Danshen on liver regeneration capacity of carbon tetrachloride-induced liver injury rats. METHOD: Computer retrieval of data from CJFD, CBM, Chinese science & technology journal full-text database and Chinese medical association digital journals, and such foreign databases as PubMed, EMBASE and SCI was included in the randomized controlled trials (RCT) of rat liver injury induced by carbon tetrachloride,with the search as at May 2012. A Meta analysis was made using Rev-Man 5.1 software. Using the GRADE system to addess five outcomes in stuay. RESULT: Two hundred and fourteen rats got involved in seven randomized trials. Meta analysis showed there were statistical differences between the Danshen group and the control group in alanine aminotransferase (ALT), aspartate aminotransferase (AST), superoxide dismutase (SOD), tumor necrosis factor-alpha (TNF-alpha) and hyaluronic acid (HA) after rat liver injury induced by carbon tetrachloride. When we used system to each outcome, because of serious limitations and indirect, they are all very low quality. CONCLUSION: Danshen shows certain promoting effect to liver regeneration in carbon tetrachloride-induced liver injury rats." | Chemical and Drug Induced Liver Injury |
Optimal age for ovariohysterectomy or castration has not been defined in the scientific literature. Bitches and queens are significantly less likely to develop mammary neoplasia, which has a high incidence and potentially high morbidity and mortality, if spayed when young. Tom cats exhibit undesirable behaviors that preclude them being good pets and should be castrated young. There is no compelling reason to castrate male dogs when young unless it is needed to control reproductive behaviors or prevent indiscriminate breeding. Alternatives to surgical sterilization that may be available in the future include intratesticular injection and immunization against gonadotropin-releasing hormone. | Sterilization, Reproductive |
OBJECTIVES: Electroconvulsive therapy (ECT) is effective in the treatment of severe psychiatric disorders. Electroconvulsive therapy is applied to almost 1 million patients every year around the world. The aim of this study was to monitor the use of ECT in psychiatric facilities for adults in the Czech Republic (CR) in 2014 and to describe the national practice. METHODS: A 14-item questionnaire was sent to all Czech inpatient psychiatric facilities that provide ECT, with the aim of getting a detailed picture of the use of ECT in the CR. The questionnaire assessed the technical background for using ECT in each center, along with indications for the treatment, the procedure, and the manner of documenting and monitoring adverse effects. The data obtained were supplemented with information about national legal and ethical regulations as well as historical background. RESULTS: Electroconvulsive therapy is used in 26 centers across the CR. More than 1000 patients were treated with ECT in 2014. All centers use instruments delivering brief pulse stimuli, monitoring electroencephalogram and electrocardiogram. All patients have to be indicated for this treatment, which is a decision the patient's psychiatrist makes. All patients have to sign an informed consent form, excluding a situation where the patient's life is endangered. Somatic state is assessed in all patients. Bitemporal electrode placement is the preferred option in all centers. CONCLUSIONS: This article covers detailed information about the use of ECT in the CR. The results will be used to harmonize national practice and reduce the stigma associated with this method in the CR. | Electroconvulsive Therapy |
The GC content of bacterial genomes varies from 25 to 75%, but the reason for this variation is unclear. Here, we show that genomes of bacteria that rely on their host for survival (obligatory pathogens or symbionts) tend to be AT rich. Furthermore, we have analysed bacterial phages, plasmids and insertion sequences, which might also be regarded as 'intracellular pathogens', and show that they too are significantly richer in AT than their hosts. We suggest that the higher energy cost and limited availability of G and C over A and T/U could be a basis for the understanding of these differences. | Base Composition |
MOTIVATION: Chimeric RNA transcripts are generated by different mechanisms including pre-mRNA trans-splicing, chromosomal translocations and/or gene fusions. It was shown recently that at least some of chimeric transcripts can be translated into functional chimeric proteins. RESULTS: To gain a better understanding of the design principles underlying chimeric proteins, we have analyzed 7,424 chimeric RNAs from humans. We focused on the specific domains present in these proteins, comparing their permutations with those of known human proteins. Our method uses genomic alignments of the chimeras, identification of the gene-gene junction sites and prediction of the protein domains. We found that chimeras contain complete protein domains significantly more often than in random data sets. Specifically, we show that eight different types of domains are over-represented among all chimeras as well as in those chimeras confirmed by RNA-seq experiments. Moreover, we discovered that some chimeras potentially encode proteins with novel and unique domain combinations. Given the observed prevalence of entire protein domains in chimeras, we predict that certain putative chimeras that lack activation domains may actively compete with their parental proteins, thereby exerting dominant negative effects. More generally, the production of chimeric transcripts enables a combinatorial increase in the number of protein products available, which may disturb the function of parental genes and influence their protein-protein interaction network. AVAILABILITY: our scripts are available upon request. | Mutant Chimeric Proteins |
BACKGROUND AND OBJECTIVES: Measurement of arterial compliance is recognized as important for clinical use and for enabling better understanding of circulatory system regulation mechanisms. Estimation of arterial compliance involves either a direct measure of the ratio between arterial volume and pressure changes or an inference from the pulse wave velocity (PWV). In this study we demonstrate an approach to assess arterial compliance by fusion of these two information sources. The approach is based on combining oscillometry as used for blood pressure inference and PWV measurements based on ECG/PPG. Enabling reliable arterial compliance measurements will contribute to the understanding of regulation mechanisms of the arterial tree, possibly establishing arterial compliance as a key measure relevant in hemodynamic monitoring. METHODS: A measurement strategy, a physiological model, and a framework based on Bayesian principles are developed for measuring changes in arterial compliance based on combining oscillometry and PWV data. A simulation framework is used to study and validate the algorithm and measurement principle in detail, motivated by previous experimental findings. RESULTS: Simulations demonstrate the possibility of inferring arterial compliance via fusion of simultaneously acquired volume/pressure relationships and PWV data. In addition, the simulation framework demonstrates how Bayesian principles can be used to handle low signal - to - noise ratio and partial information loss. CONCLUSIONS: The developed simulation framework shows the feasibility of the proposed approach for assessment of arterial compliance by combining multiple data sources. This represents a first step towards integration of arterial compliance measurements in hemodynamic monitoring using existing clinical technology. The Bayesian approach is of particular relevance for such patient monitoring settings, where measurements are repeated frequently, context is relevant, and data is affected by artefacts. In addition, the simulation framework is necessary for future clinical-study design, in order to determine device specifications and the extent to which noise affects the inference process. | Compliance |
The functional residual capacity (FRC) was measured in 24 healthy subjects, 1-by the helium dilution method using a closed system and an open system during washout, and 2-using a constant pressure plethysmograph. Results obtained with the three methods were not significantly different. Furthermore, FRC was determined by helium dilution in 177 healthy men and in 100 healthy women, aged between 18 and 77 years. In both sexes, FRC was dependent on age, height (H) and weight, being greater in the taller, older subjects. For a given height and age, FRC decreased with increasing weight. Correlation coefficients between logarithm of (FRC/H3) and age and/or weight were highly significant. From these allometric relationships, it was possible to calculate FRC reference values, and then, reference values for other functional tests such as steady state TLCO and lung compliance. | Residual Volume |
Multidrug resistance (MDR) of tumor cells is one of the major problems encountered during cancer chemotherapy. In this paper, we isolated eight triterpenoids from Poria cocos and evaluated their effects on reversing MDR of KBV200 cells. Eight triterpenoids increase significantly vincristine-induced cytotoxicity in drug-resistant KBV200 cells at the concentrations of 12.5 microg/mL and 25 microg/mL. Dehydrotumulosic acid showed the best reversal effect: it increased KBV200 apoptosis induced by vincristine and inhibited P-gp function through enhancing the accumulation and retention of fluorescent P-gp substrate rhodamine 123 in KBV200 cells but had no effect on P-gp expression. | Cell Extracts |
Viral infection usually influences cellular protein synthesis either actively or passively via modification of various translation initiation factors. Here we demonstrated that infection with avian reovirus (ARV) interfered with cellular protein synthesis. This study demonstrated for the first time that ARV influenced the phosphorylation of translation initiation factors including eIF4E and eIF-4G. Interestingly, ARV also induced phosphorylation of eukaryotic translation elongation factor (eEF2) in a time- and dose-dependent manner. Inhibition of mTOR by rapamycin notably increased the level of phosphorylated eEF2 in infected cells. However, rapamycin did not show any negative effects on ARV replication, suggesting that phosphorylation of eEF2 in infected cells did not reduce ARV propagation. These results demonstrated for the first time that ARV promotes phosphorylation of eEF2 which in turn influenced host protein production not simply by modulating the function of translation initiation factors but also by regulating elongation factor eEF2. | Peptide Elongation Factor 2 |
In this review, we introduce our recent studies on divinyl chlorophylls functioning in unique marine picoplankton Prochlorococcus sp. (1) Essential physicochemical properties of divinyl chlorophylls are compared with those of monovinyl chlorophylls; separation by normal-phase and reversed-phase high-performance liquid chromatography with isocratic eluent mode, absorption spectra in four organic solvents, fluorescence information (emission spectra, quantum yields, and life time), circular dichroism spectra, mass spectra, nuclear magnetic resonance spectra, and redox potentials. The presence of a mass difference of 278 in the mass spectra between [M+H](+) and the ions indicates the presence of a phytyl tail in all the chlorophylls. (2) Precise high-performance liquid chromatography analyses show divinyl chlorophyll a' and divinyl pheophytin a as the minor key components in four kinds of Prochlorococcus sp.; neither monovinyl chlorophyll a' nor monovinyl pheophytin a is detected, suggesting that the special pair in photosystem I and the primary electron acceptor in photosystem II are not monovinyl but divinyl-type chlorophylls. (3) Only Prochlorococcus sp. NIES-2086 possesses both monovinyl chlorophyll b and divinyl chlorophyll b, while any other monovinyl-type chlorophylls are absent in this strain. Monovinyl chlorophyll b is not detected at all in the other three strains. Prochlorococcus sp. NIES-2086 is the first example that has both monovinyl chlorophyll b as well as divinyl chlorophylls a/b as major chlorophylls. | Chlorophyll |
AIMS: To investigate the antibacterial activity of three (palmarosa, basil and rosemary) essential oils (EOs) on Aeromonas veronii and Aeromonas caviae, and determine minimum inhibitory concentration (MIC) of potent EO against tetracycline and sulfonamide resistant strains. METHODS AND RESULTS: Palmarosa oil (PMO) showed significantly (p < 0.05) higher inhibition zones against both A. veronii and A. caviae (n = 30) than basil and rosemary in the disk diffusion assay. The MIC (% v/v) of PMO ranged from 0.008% to 1.00%. The mean MIC was significantly higher for A. caviae (0.48 +/- 0.24%) than A. veronii (0.21 +/- 0.15%). Further, the MIC of PMO was compared in six groups: Group 1: Tetracycline Resistant A. veronii (TRV); Group 2: Tetracycline Resistant A. caviae (TRC); Group 3: Sulfonamide Resistant A. veronii (SRV); Group 4: Sulfonamide Resistant A. caviae (SRC); Group 5: Susceptible A. veronii (SV) and Group 6: Susceptible A. caviae (SC). No significant differences were observed between overall resistant (TRV+ SRV) and susceptible A. veronii (SV). However, in A. caviae, the resistant group had a lower MIC than the susceptible group. Moreover, the MIC was significantly lower for TRC (0.31 +/- 0.11%) as compared to SRC (0.46 +/- 0.10%). The time of kill of PMO for both the species of Aeromonas was 20-30 min. CONCLUSION: Palmarosa oil exhibited significantly higher activity on A. veronii than A. caviae. The resistant strains of A. caviae were inhibited at a lower concentration than susceptible strains. SIGNIFICANCE AND IMPACT OF THE STUDY: Palmarosa oil could be explored as an alternative antimicrobial agent for mitigating antimicrobial resistance and managing Aeromonas infection in fish and their risks to public health. | Aeromonadaceae |
Current evidence has shown antioxidant activity of artichoke as a potent source of antioxidant compounds. However, it seems that the antioxidant activity of artichoke has not yet been reviewed. Therefore, the present study was designed to perform a systematic review of human studies, animal models, and in vitro systems and to conduct a meta-analysis of animal studies on the antioxidant effects of artichoke. We searched four electronic databases till April 2018 using relevant keywords. All English language articles were assessed. For animal studies, standardized mean difference was pooled using a random effects model. The included studies were evaluated for eligibility and risk of bias. Thirty-nine articles (two human, 23 animal, and 14 in vitro studies) were reviewed. The results of in vitro systems supported the antioxidant effect of artichoke, whereas limited clinical trials indicated no change or a slight improvement of antioxidant status. Finding of animal studies indicated that artichoke extract supplementation increased superoxide dismutase, catalase, glutathione, and glutathione peroxidase level in liver, as well as, decreased malondialdehyde level in liver and plasma of animals with induced disease significantly compared with comparison group. This meta-analysis provided convincing evidence for antioxidant activity of artichoke in animals. | Cynara scolymus |
The drug-drug interaction (DDI) potential between the fixed-dose combinations of ledipasvir/sofosbuvir 90/400 mg for hepatitis C virus and emtricitabine/rilpivirine/tenofovir alafenamide (TAF) 200/25/25 mg for HIV was evaluated in a randomized, open-label, single-center, multiple-dose, 3-way, 6-sequence, crossover Phase 1 study in 42 healthy subjects. Emtricitabine/rilpivirine/TAF had no relevant effect on the pharmacokinetic parameters of maximum concentration [C(max) ] and area under the concentration versus time curve over the dosing interval [AUC(tau) ] for ledipasvir, sofosbuvir, and the metabolites GS-566500 and GS-331007. Ledipasvir/sofosbuvir had no effect on the C(max) and AUC(tau) for rilpivirine and emtricitabine. The C(max) and AUC(tau) of tenofovir, the major metabolite of TAF, were increased by 62% and 75%, respectively. However, the resulting absolute tenofovir exposures were markedly lower than the historical tenofovir exposures following tenofovir disoproxil fumarate (TDF) and, as such, were not considered to be clinically relevant. In contrast, additional adverse effect monitoring is recommended upon coadministration of ledipasvir and TDF due to elevated tenofovir exposures resulting from the DDI. This difference is explained by the fact that TAF 25 mg results in markedly lower (~90%) plasma tenofovir exposure compared to TDF 300 mg. Ledipasvir/sofosbuvir and emtricitabine/rilpivirine/TAF were generally well tolerated when administered alone or in combination. HIV/hepatitis C virus-coinfected patients can coadminister ledipasvir/sofosbuvir and emtricitabine/rilpivirine/TAF without dosage adjustments. | Rilpivirine |
The death certificate must be established within 24 hours following the death and handed to the mayor. The obligation to place in the coffin immediately is planned by a defined list of contagious diseases. Medicolegal obstacle must be ticked if there is a doubt on the cause of death. In order to look into the causes of the death, swabs can be asked by the physician. It is a medical or scientific autopsy to look into the causes of the death apart from a juridical procedure. The presence of a battery prosthesis (pacemaker) must be specified, so that it can be removed by a physician or a thanatopractionner before the placing in the coffin. Death certificate is passed on by the city hall to Insee, which updates the identification national register of physical people. Inserm receives anonymous data of the causes of death allowing to establish the mortality national statistics. In the absence of medicolegal obstacle or obligation to place in the coffin immediately, funeral operations can begin: preservation care, body transport, placing in the coffin and finally burial or cremation. | Death Certificates |
Following deep vein thrombosis (DVT), one of every two patients will develop postthrombotic syndrome (PTS), which causes remarkable consequences on the socioeconomic level. Residual thrombosis is an important predictor of PTS, and severe early symptoms, old age, obesity, improper anticoagulation, recurrent thrombosis and varicose veins are major risk factors. Diagnosis of PTS is mainly based on the clinical findings for patients with a history of DVT, while in those without it, instrumental diagnosis might help in detecting a previous DVT. Prompt administration of adequate compression elastic stockings (ECS) in patients with symptomatic DVT reduces the frequency of PTS by half. Usually, the management of an established PTS is demanding, and often discouraging. However, when carefully supervised and instructed to wear proper ECS, more than 50% of patients either remain quiescent or improve during long-term follow-up. | Postthrombotic Syndrome |
CONTEXT: Most patients with neurogenic lower urinary tract dysfunction (NLUTD) require life-long care to maintain their quality of life (QoL) and to maximise life expectancy. OBJECTIVE: To provide a summary of the 2008 version of the European Association of Urology (EAU) guidelines on NLUTD and to assess the effectiveness of currently available diagnostic tools, particularly ultrasound imaging and urodynamics. EVIDENCE ACQUISITION: The recommendations provided in the 2008 EAU guidelines on NLUTD are based on a review of the literature, using online searches of Medline and other source documents published between 2004 and 2007. A level of evidence and/or a grade of recommendation have been assigned to the guidelines where possible. EVIDENCE SYNTHESIS: NLUTD encompasses a wide spectrum of pathologies, and patients often require life-long, intensive medical care to maximise their life-expectancy and to maintain their QoL. Treatment must be tailored to the needs of the individual patient and, in many cases, involves a multidisciplinary team of experts. Timely diagnosis and treatment are essential if irreversible deterioration of both the upper and lower urinary tracts are to be avoided. Therapeutic decisions are made on the basis of a comprehensive medical assessment, including urodynamics to identify the type of dysfunction. Advances in investigative technologies have facilitated the noninvasive and conservative management of patients who have NLUTD. CONCLUSIONS: The diagnosis and treatment of NLUTD, which is a highly specialised and complex field involving both urology and medicine, requires up-to-date expert advice to be readily available. The current guidelines are designed to fulfil this need. | Urinary Bladder, Neurogenic |
A rapid method was developed for separation of lipoproteins by flotation in an ultracentrifuge using a four-step density gradient 1.006, 1.063, 1.250 and 1.300 g/ml. A satisfactory fractionation of serum lipoproteins was carried out by single ultracentrifugation within 4-5 hrs at 216,000 g." | Centrifugation, Density Gradient |
Another fine mess the Department of Health has got doctors into | Career Mobility |
PURPOSE OF REVIEW: Autonomic disorders offer a fascinating view of the complexity of the nervous system. Their impact on human health ranges from benign to severe. Deciphering autonomic symptoms and signs draws on the cognitive skills and personal interest in the plight of patients that first attracted many physicians to the field of neurology. This article provides tools to sharpen those skills. RECENT FINDINGS: Autonomic neuroscience and accumulated clinical knowledge have led to the categorization of autonomic disorders into specific syndromes that can be identified on the basis of clinical phenotypes and physiologic responses to standardized stimuli in the autonomic laboratory. A key development has been the ability to distinguish neurogenic orthostatic hypotension from other causes of hypotension. Quantification of sudomotor responses has proven valuable in the diagnosis of thermoregulatory disorders and small fiber neuropathies such as those related to diabetes mellitus. Increasing attention has focused on autonomic failure as a defining feature of neurodegenerative alpha-synucleinopathies, especially multiple system atrophy. As awareness of autonomic disorders has increased, the once obscure term dysautonomia has entered into common parlance. SUMMARY: With appropriate knowledge and experience, neurologists can diagnose autonomic dysfunction accurately and with confidence. The opportunity to play an important role in caring for patients with autonomic disorders is worth the effort." | Autonomic Nervous System Diseases |
The medical and clinical promise of stem cell research is widely heralded, but moral judgments about it collide. This article takes general stock of such judgments and offers one specific resolution. It canvasses a spectrum of value judgments on sources, complicity, adult stem cells, and public and private contexts. It then examines how debates about abortion and stem cell research converge and diverge. Finally, it proposes to extend the principle of nothing is lost" to current debates. This extension links historical discussions of the ethics of direct killing with unprecedented possibilities that in vitro fertilization procedures yield. A definite normative region to inhabit is located, within a larger range of rival value judgments. The creation of embryos for research purposes only should be resisted, yet research on "excess' embryos is permissible by virtue of an appeal to the "nothing is lost" principle." | Research Embryo Creation |
Intrinsic factor (IF) secretion in healthy male subjects was studied in response to pentagastrin stimulation with and without cimetidine, and to impromidine, a histamine H2 receptor agonist. Peak and total IF output were reduced by cimetidine, but the concentration was unchanged and the response was unaffected by administration of the compound for 1 week. The IF secretory response to impromidine was similar to that to pentagastrin. It is suggested that the acid and IF components of the parietal cell secretory response are mediated via different intracellular pathways, that histamine H2 receptors do not fulfill and obligatory role in the secretion of IF and that synthesis of IF is probably not altered by cimetidine. | Receptors, Histamine H2 |
Phosphorylation of cyclin-dependent kinases (CDKs) by the CDK-activating kinase is required for the activation of CDK enzymes. Members of two families of CDK inhibitors, p16/p18 and p21/p27, become physically associated with and inhibit the activity of CDKs in response to a variety of growth-modulating signals. Here, we show that the representative members of both families of CDK inhibitors, p21waf1,cip1, p27kip1, and p18, can prevent the phosphorylation of their CDK partners, CDK2 and CDK6, by CDK-activating kinase. No direct interaction between CDK-activating kinase and the CDK inhibitors could be detected, suggesting that binding of these CDK inhibitors to CDK subunits renders CDK inaccessible to the CDK-activating kinase phosphorylation. These findings suggest that a general mechanism of CDK inhibitor function is to block the phosphorylation of CDK enzymes by CDK-activating kinase." | Cyclin-Dependent Kinase Inhibitor p18 |
The present prospective study was done to compare the size of the extrahepatic bile duct as measured by ultrasound with those measured by different radiographic techniques. The sonographic diameters were significantly correlated to the diameters measured by intravenous cholangiography (r = 0.92), to the diameters measured by endoscopic retrograde cholangiography (r = 0.81), and to the diameters measured by percutaneous transhepatic cholangiography (r = 0.85). The mean radiographic diameters were significantly greater for intravenous cholangiography, endoscopic retrograde cholangiography, and percutaneous transhepatic cholangiography than the mean sonographic diameters. Analyzing the regression lines between the radiographic and sonographic diameters and studying the sonographic diameters during intravenous cholangiography, the discrepancy between sonographic and radiographic measurements appears to be due to several factors: (a) radiographic magnification, (b) choleretic effects in intravenous cholangiography, (c) sonographic minification, (d) dilatation of the extrahepatic bile duct due to direct injection of a contrast agent in endoscopic retrograde cholangiography and percutaneous transhepatic cholangiography, and (e) premedication in endoscopic retrograde cholangiography and percutaneous transhepatic cholangiography. Because the normal size of the extrahepatic bile duct is not usually assessed in healthy subjects by intravenous cholangiography, endoscopic retrograde cholangiography, and percutaneous transhepatic cholangiography, the mean diameter and the upper normal limit of the extrahepatic bile duct were calculated for intravenous cholangiography, endoscopic retrograde cholangiography, and percutaneous transhepatic cholangiography using previous sonographic data from healthy subjects and the present regression lines. The calculated upper limit for normal was 7-8 mm in intravenous cholangiography and 10-11 mm in endoscopic retrograde cholangiography and in percutaneous transhepatic cholangiography. | Cholestasis, Extrahepatic |
Prior to the emergence of H3N8 canine influenza virus (CIV) and the latest avian-origin H3N2 CIV, there was no evidence of a circulating canine-specific influenza virus. Molecular and epidemiological evidence suggest that H3N8 CIV emerged from H3N8 equine influenza virus (EIV). This host-range shift of EIV from equine to canine hosts and its subsequent establishment as an enzootic CIV is unique because this host-range shift was from one mammalian host to another. To further understand this host-range shift, we conducted a comprehensive phylodynamic analysis using all the available whole-genome sequences of H3N8 CIV. We found that (1) the emergence of H3N8 CIV from H3N8 EIV occurred in approximately 2002; (2) this interspecies transmission was by a reassortant virus of the circulating Florida-1 clade H3N8 EIV; (3) once in the canine species, H3N8 CIV spread efficiently and remained an enzootic virus; (4) H3N8 CIV evolved and diverged into multiple clades or sublineages, with intra and inter-lineage reassortment. Our results provide a framework to understand the molecular basis of host-range shifts of influenza viruses and that dogs are potential mixing vessels" for the establishment of novel influenza viruses." | Host Specificity |
PURPOSE: The overall aim of this study was to clarify and better characterize the sleep/circadian patterns of adolescents in a nationally representative sample. METHODS: We used three waves of data from the National Longitudinal Study of Adolescent Health to assess sleep/circadian patterns of 2,700 adolescents in grades seven through 12. RESULTS: Late school year bedtime was associated with shorter total sleep time cross-sectionally, whereas late summertime bedtime was not. Moreover, late school year bedtime was not associated with late summertime bedtime cross-sectionally. Late school year bedtime in Wave I (1994-1995) was associated with worse educational outcomes and emotional distress 6-8 years later. In addition, late summertime bedtime in Wave II (1996) was associated with more emotional distress at Wave III (2001-2002). Short total sleep time was not associated longitudinally with changes in emotional and academic functioning. Across Waves I and II, more than three quarters of adolescents who went to sleep at 11:15 a.m. or later during the school year or 1:30 a.m. or later during the summer reported sleeping fewer than the recommended 9 hours. CONCLUSIONS: These findings underscore the significance of evaluating and monitoring bedtime in adolescents and the importance of intervention strategies that target bedtimes in an effort to reduce associated functional impairments, and improve academic and emotional outcomes." | National Longitudinal Study of Adolescent Health |
Two toxic proteins were purified from the seeds of Abrus precatorius by DEAE-A 50 and Sepharose 4B chromatography. One of them does not bind on the Sepharose 4B column (Abrin-b) and the other (Abrin-a) is eluted with 0.2 M galactose. The amino acid compositions and tryptic maps of these two proteins were similar, but not identical. The molecular weights estimated by SDS-gel electrophoresis were 67,000 for abrin-b as compared with 65,000 for abrin-a. In the presence of mercaptoethanol, both abrin-a and abrin-b gave rise to two bands. The lethal doses of abrin-a and abrin-b for mice recorded within 48 h were 10 and 25 microgram per kg of body weight respectively. Abrin-a at 0.8 microgram per ml concentration level agglutinated human 0-type erythrocytes, whereas abrin-b showed no such activity. Abrin-a at 5 microgram per ml concentration level agglutinated both the Sarcoma 180 cells and Ehrlich ascites tumor cells, but it required 150 microgram per ml for abrin-b. Both these two proteins at a sublethal dose could inhibit the growth of Ehrlich ascites tumor cells which were injected simultaneously with these proteins. 131I-abrin-a and 131I-abrin-b were able to bind Sarcoma 180 cells, and the binding of abrin-a could be inhibited by lactose, raffinose, galactose and rhamnose, but none of 15 sugars tested inhibited the binding of abrin-b. | Abrin |
Dentistry in this country is approaching a major cross roads. Although not everyone will take the same route, now is the time to examine the options and identify a way ahead for the majority. This article seeks to examine the history which has led to the numerous changes and pressures evident in dentistry today; it examines the various components and argues that these lead inexorably to certain conclusions. | State Dentistry |
Hepatorenal syndrome (HRS), the extreme manifestation of renal impairment in patients with cirrhosis, is characterized by reduction in renal blood flow and glomerular filtration rate. Hepatorenal syndrome is diagnosed when kidney function is reduced but evidence of intrinsic kidney disease, such as hematuria, proteinuria, or abnormal kidney ultrasonography, is absent. Unlike other causes of acute kidney injury (AKI), hepatorenal syndrome results from functional changes in the renal circulation and is potentially reversible with liver transplantation or vasoconstrictor drugs. Two forms of hepatorenal syndrome are recognized depending on the acuity and progression of kidney injury. The first represents an acute impairment of kidney function, HRS-AKI, whereas the second represents a more chronic kidney dysfunction, HRS-CKD (chronic kidney disease). In this review, we provide critical insight into the definition, pathophysiology, diagnosis, and management of hepatorenal syndrome. | Hepatorenal Syndrome |
In the past, especially in the 1970s, tooth mobility has been largely studied by various research groups. Since then, scientific interest in this domain has progressively decreased. However, from a clinical point of view tooth mobility has remained an important concern. This paper aims to review and update basic theoretical notions of tooth mobility after evaluation of recent studies. Finally, clinical implications are discussed. | Tooth Mobility |
Mucosal melanoma is a rare but devastating subtype of melanoma which typically has a worse prognosis than other melanoma subtypes. Large-scale next-generation sequencing studies, including our recent research, have also proved that the molecular landscape and potential oncogenic drivers of mucosal melanoma remain distinct from that of cutaneous melanoma. Recently, a number of selective cyclin-dependent kinase 4 (CDK4)/6 inhibitors have been approved for clinical application in breast cancer or entered phase III clinical trial in other solid tumors. Additionally, we have revealed that the dysregulation of cell cycle progression, caused by CDK4 amplification, is a key genetic feature in half of mucosal melanoma and targeting of CDK4 in selected mucosal melanoma patients is a potentially promising direction for precision cancer treatment by using molecular-characterized mucosal melanoma patient-derived-xenograft models. This review summarizes the current literature regarding CDK4/6 dysregulation in mucosal melanoma, preclinical and clinical studies of CDK4/6 inhibitors and potential combinational strategies in treating mucosal melanoma. | Cyclin-Dependent Kinase 4 |
BACKGROUND: The mutation of the tyrosinase (TYR) gene results in oculocutaneous albinism type 1 (OCA1), an autosomal recessive genetic disorder. OCA1 is the most common type of OCA in the Chinese population. Hence, the TYR gene was tested in this study. We also delineated the genetic analysis of OCA1 in a Chinese family. METHODS: Genomic DNA was isolated from the blood leukocytes of a proband and his family. Mutational analysis at the TYR locus by DNA sequencing was used to screen five exons, including the intron/exon junctions. A pedigree chart was drawn and the fundus of the eyes of the proband was also examined. RESULTS: A novel missense mutation p.I151S on exon 1, and homozygous TYR mutant alleles were identified in the proband. None of the mutants was identified among the 100 normal control subjects. Genetic analysis of the proband's wife showed normal alleles in the TYR gene. Thus, the fetus was predicated a carrier of OCA1 with a normal appearance. CONCLUSION: This study provided new information about a novel mutation, p.I151S, in the TYR gene in a Chinese family with OCA1. Further investigation of the proband would be helpful to determine the effects of this mutation on TYR activity. | Mutation, Missense |
Iroquois homeobox (Irx) genes are TALE-class homeobox genes that are evolutionarily conserved across species and have multiple critical cellular functions in fundamental tissue development processes. Previous studies have shown that Irxs genes are expressed during tooth development. However, the precise roles of genes in teeth remain unclear. Here, we demonstrated for the first time that Irx3 is an essential molecule for the proliferation and differentiation of odontoblasts. Using cDNA synthesized from postnatal day 1 (P1) tooth germs, we examined the expression of all Irx genes (Irx1-Irx6) by RT-PCR and found that all genes except Irx4 were expressed in the tooth tissue. Irx1-Irx3 a were expressed in the dental epithelial cell line M3H1 cells, while Irx3 and Irx5 were expressed in the dental mesenchymal cell line mDP cells. Only Irx3 was expressed in both undifferentiated cell lines. Immunostaining also revealed the presence of IRX3 in the dental epithelial cells and mesenchymal condensation. Inhibition of endogenous Irx3 by siRNA blocks the proliferation and differentiation of mDP cells. Wnt3a, Wnt5a, and Bmp4 are factors involved in odontoblast differentiation and were highly expressed in mDP cells by quantitative PCR analysis. Interestingly, the expression of Wnt5a (but not Wnt3a or Bmp4) was suppressed by Irx3 siRNA. These results suggest that Irx3 plays an essential role in part through the regulation of Wnt5a expression during odontoblast proliferation and differentiation. | Odontoblasts |
Two analytical approaches for the rapid measurement of hydrogen sulfide (H(2)S) have been compared to a reference method for their potential application as a rapid procedure for the quantification of H(2)S formed during alcoholic fermentations. In one case, silver nitrate, lead acetate, and mercuric chloride selective detector tubes for the analysis of H(2)S in air were investigated. In the other case, a commercially available kit for the diagnosis of nitrogen starvation in wine fermentations, which is based on the detection of H(2)S, was investigated. Both methods exhibited excellent linearity of response, but the mercuric chloride tube was found to suffer from interferences due to the concomitant presence of mercaptans, which resulted in erroneous H(2)S quantification. A comparative study between the two methods studied and the cadmium hydroxide/methylene blue reference method commonly used to monitor H(2)S indicate that the two new methods displayed better recoveries at low H(2)S concentrations, besides being more rapid and economical. The two new methods were successfully used to quantify production of H(2)S in different grape juice fermentations. The suitability of each method for the study of specific aspects of H(2)S production during fermentation is discussed. | Mercuric Chloride |
A network approach, which simplifies geographic settings as a form of nodes and links, emphasizes the connectivity and relationships of spatial features. Topological networks of spatial features are used to explore geographical connectivity and structures. The PageRank algorithm, a network metric, is often used to help identify important locations where people or automobiles concentrate in the geographical literature. However, geographic considerations, including proximity and location attractiveness, are ignored in most network metrics. The objective of the present study is to propose two geographically modified PageRank algorithms-Distance-Decay PageRank (DDPR) and Geographical PageRank (GPR)-that incorporate geographic considerations into PageRank algorithms to identify the spatial concentration of human movement in a geospatial network. Our findings indicate that in both intercity and within-city settings the proposed algorithms more effectively capture the spatial locations where people reside than traditional commonly-used network metrics. In comparing location attractiveness and distance decay, we conclude that the concentration of human movement is largely determined by the distance decay. This implies that geographic proximity remains a key factor in human mobility. | Geographic Mapping |
The events occurring during tumor formation and progression display similarities to some of the steps in embryonic morphogenesis. The family of AP-2 proteins consists of five different transcription factors (alpha, beta, gamma, delta, and epsilon) that play relevant roles in embryonic development, as demonstrated by the phenotypes of the corresponding knockout mice. Here, we show that AP-2alpha and AP-2gamma proteins play an essential role in tumorigenesis. Down-modulation of AP-2 expression in tumor cells by RNA interference (RNAi) led to enhanced tumor growth and reduced chemotherapy-induced cell death, as well as migration and invasion. Most of these biological modulations were rescued by AP-2 overexpression. We observed that increased xenotransplant growth was mostly due to highly enhanced proliferation of the tumor cells together with reduced innate immune cell recruitment. Moreover, we showed that migration impairment was mediated, at least in part, by secreted factors. To identify the genetic programs involved in tumorigenesis, we performed whole genome microarray analysis of AP-2alpha knockdown cells and observed that AP-2alpha regulates specific genes involved in cell cycle, cell death, adhesion, and migration. In particular, we showed that ESDN, EREG, and CXCL2 play a major role in AP-2 controlled migration, as ablation of any of these genes severely altered migration. | Transcription Factor AP-2 |
This study pioneered an approach that determined the effects of excess manganese (Mn) on three species; Datura stramonium, Alhagi camelthorn and Chenopodium ambrosioides. We investigated their levels of Mn, antioxidative enzymes and oxidative damage biomarkers in plants (zone 1) in and outside (zone 2) the Mn mine. The results showed that total and available Mn were at toxic levels for plants growing on zone 1. The Mn levels in each plant species were higher in leaves, stems and roots. Mn was only accumulated significantly in leaf vacuoles of A. camelthorn. Antioxidative enzyme activities of C. ambrosioides and/or D. stramonium in zone 1 were higher in leaves, stems and then in their roots. Malondialdehyde (MDA) and dityrosine levels were insignificantly higher in tissues of the studied plants in zone 1 with respect to zone 2. The roots of studied plants showed significantly higher levels of these biomarkers in comparison with their leaves in zone 1. Accordingly, antioxidative enzymatic response to Mn-stress in D. stramonium and C. ambrosioides and possibly accumulation of Mn in leaf vacuoles of A. camelthorn, protected them from oxidative damages and involved in their tolerance in Mn mine. | Chenopodium ambrosioides |
In this two-part series, Argyrios N. Theofilopoulos summarizes the current state of affairs in the field of autoimmunity. Part I integrates the collective mechanistic theories of autoimmune diseases. The most straightforward explanation to emerge with regard to organ-specific diseases is the concept that these are caused by inappropriate, yet conventional, immunological responses against self-antigens for which tolerance has never been established. A similar mechanism may be operative in systemic autoimmunity, but other abnormalities such as defects in the apoptosis machinery may also be invoked. Part II will address the genetic contributions predisposing to autoimmune syndromes. | Lymphocyte Activation |
Ambrein is found in ambergris, a coprolith occurring in the rectum of the sperm whale. In vitro, ambrein is produced by enzymatic cyclisation of squalene, via a monocyclic intermediate. However, little is known of the in vivo process. In order to find evidence for the reaction in vivo, a comparison was made of the delta(13)C relative isotopic ratios of ambrein in ambergris with those of co-occurring sterols. A statistically significant difference was noted. This suggests that ambrein originates via a different biosynthetic mechanism from that of the sterols. Examination of the minor constituents of a hydrogenolysed extract of ambergris revealed compounds with a bicyclic polypodane nucleus, rather than those with monocyclic structures. It is hypothesised that in vivo biosynthesis of ambrein proceeds, at least in some cases, via bacterial production of bicyclic polypodenols. The latter are known products of non-concerted squalene (or squalene oxide) cyclisations in other organisms. | Ambergris |
BACKGROUND: In TKA, soft tissue balance (the joint gap) depends on the amount of resected bone and soft tissue release. Some studies report preoperative bony deformity correlates with soft tissue balance evaluated intraoperatively and that the medial tissues are contracted with varus deformity. However, these studies did not take into account the amount of resected bone and did not describe whether the soft tissue was tight or loose. Therefore, it remains unclear whether in varus deformity the soft tissues on the medial side are contracted. QUESTIONS/PURPOSES: We compared (1) intraoperative joint gap, (2) amount of resected bone, and (3) intraoperative soft tissue laxity on the lateral and medial sides according to severity of preoperative varus deformity. METHODS: We retrospectively reviewed 70 patients with osteoarthritis and varus deformities who underwent 90 TKAs. We retrospectively divided the 90 knees into three groups according to degree of preoperative alignment: mild varus group (<10 degrees ), moderate varus group (10 degrees -20 degrees ), and severe varus group (>20 degrees ). To evaluate intraoperative soft tissue tension, we calculated the soft tissue gap by subtracting the thickness of the resected bone from the joint gaps on the medial and lateral sides, respectively. We then explored the relationship between the soft tissue gap and preoperative alignment. RESULTS: The lateral soft tissue gap was larger in the severe varus group than in the mild and moderate varus groups. The medial soft tissue gap was larger in the severe varus group than in the mild varus group, but there were no differences in the medial joint gaps among the groups. CONCLUSIONS: After the bone is resected, the soft tissue on the lateral side is more lax; however, the soft tissue on the medial side is not shorter with greater preoperative varus deformity. | Hallux Varus |
Evodiamine (EVO) is an active medicinal compound derived from the traditional herbal medicine Evodia rutaecarpa. It has been reported that evodiamine has several beneficial biological properties, including anticancer and anti-inflammatory activities. However, the in vitro and in vivo anticancer activities of EVO against the growth of glioblastoma cells remain undefined. EVO induced significant decreases in the viability of U87 and C6 glioma cells, but not of primary astrocytes, according with the occurrence of apoptotic characteristics including DNA ladders, caspase-3 and poly(ADP ribose) polymerase (PARP) protein cleavage, and hypodiploid cells. The disruption of the mitochondrial membrane potential (MMP) was detected, and it was found that the peptidyl caspase-9 inhibitor, Z-LEHD-FMK, significantly prevented glioma cells from EVO-induced apoptosis. Increased c-Jun N-terminal kinase (JNK) protein phosphorylation by EVO was observed, and the addition of JNK inhibitors, SP600125 and JNKI inhibited the EVO-induced apoptosis was inhibited. Additionally, EVO treatment induced G2/M arrest with increased polymerized tubulin protein expression in U87 and C6 cells. Elevated expressions of the cyclin B1, p53, and phosphorylated (p)-p53 proteins were detected in EVO-treated glioma cells, and these were inhibited by JNK inhibitors. An in vivo study showed that EVO significantly reduced the growth of gliomas elicited by the subcutaneous injection of U87 cells with increases in cyclin B1, p53, and p-p53 protein expressions in tumors. An analysis of eight EVO-related chemicals showed that alkyl groups at position 14 in EVO are important for its anti-glioma effects which involve both apoptosis and G2/M arrest. Evidence is provided that supports EVO induction of apoptosis and G2/M arrest via the activation of JNK-mediated gene expression and disruption of MMP in glioblastoma cells. EVO was shown to penetrate the blood-brain barrier; EVO is therefore predicted to be a promising compound for the chemotherapy of glioblastomas and deserves further investigations. | Evodia |
Severe acute respiratory syndrome (SARS) is a newly recognised and highly contagious respiratory infection caused by a new strain of coronavirus. The disease can result in progressive respiratory failure in adults and the mortality rate has been reported to be 8-15%. This infection spreads by droplet transmission and children appear to acquire SARS through close household contact exposure to infected adults. Disease severity is, however, much milder in the paediatric age group. The common laboratory findings in infected children and adolescents include lymphopaenia and elevated levels of lactate dehydrogenase and creatinine phosphokinase. Air space consolidation is commonly seen during the course of the illness although chest radiographs are normal on presentation in half of the cases. The pathophysiology of SARS appears to be related to immunological dysregulation in response to the coronavirus infection. The optimal treatment of SARS in children remains to be determined. No case fatality in infected children has been reported. The early and proper isolation of infected adults, meticulous infection control measures in the hospital setting, exhaustive contact tracing and quarantine measures are important steps in preventing the spread of the disease among health care workers and into the community. The development of a sensitive and rapid test for early diagnosis is underway. Further controlled trials are necessary to define the optimal treatment of this infection in children." | Severe Acute Respiratory Syndrome |
Determination of the residual gamma isomer of benzene hexachloride (gamma-BHC) by gas chromatography showed that the insecticide persisted longer in sterilized flooded soils than in nonsterilized flooded soils. A second addition of gamma-BHC to one of the nonsterilized soils. (55 days after the first application) disappepsilonared more rapidly than the first addition. These results strongly indicate biodegradation of gamma-BHC in flooded soils. | Soil Microbiology |
The ultraviolet B (UVB) sensitivity of rice cultivated in Asia and Africa varies greatly, with African rice cultivars (Oryza glaberrima Steud. and O. barthii A. Chev.) being more sensitive to UVB because of their low cyclobutane pyrimidine dimer (CPD) photolyase activity, which is a CPD repair enzyme, relative to Asian rice cultivars (O. sativa L.). Hence, the production of UVB-resistant African rice with augmented CPD photolyase activity is of great importance, although difficulty in transforming the African rice cultivars to this end has been reported. Here, we successfully produced overexpressing transgenic African rice with higher CPD photolyase activity by modifying media conditions for callus induction and regeneration using the parental line (PL), UVB-sensitive African rice TOG12380 (O. glaberrima). The overexpressing transgenic African rice carried a single copy of the CPD photolyase enzyme, with a 4.4-fold higher level of CPD photolyase transcripts and 2.6-fold higher activity than its PL counterpart. When the plants were grown for 21 days in a growth chamber under visible radiation or with supplementary various UVB radiation, the overexpressing transgenic plants have a significantly increased UVB resistance index compared to PL plants. These results strongly suggest that CPD photolyase remains an essential factor for tolerating UVB radiation stress in African rice. As a result, African rice cultivars with overexpressed CPD photolyase may survive better in tropical areas more prone to UVB radiation stress, including Africa. Collectively, our results provide strong evidence that CPD photolyase is a useful biotechnological tool for reducing UVB-induced growth inhibition in African rice crops of O. glaberrima." | Deoxyribodipyrimidine Photo-Lyase |
In children the rate of acute, transient ITP is much higher than the chronic form of ITP. Often acute childhood ITP is a para- or postinfectious event. Pathophysiologically bleeding symptoms mainly depend on the ratio between normal or increased platelet production and early destruction of platelets. The management of ITP has to be focused on the individual bleeding symptoms rather than to the platelet count (see staging system). Today's treatments are directed against the disturbed immune response. As recent guidelines and surveys demonstrate opinion based recommendations have to be challenged by evidence based clinical research in ITP (see www.unibas.ch/itpbasel). | Hemorrhagic Disorders |
Relativistic effects are found to be important for the estimation of NMR parameters in halogen-bonded complexes, mainly when they involve the heavier elements, iodine and astatine. A detailed study of 60 binary complexes formed between dihalogen molecules (XY with X, Y = F, Cl, Br, I and At) and four Lewis bases (NH(3), H(2)O, PH(3) and SH(2)) was carried out at the MP2/aug-cc-pVTZ/aug-cc-pVTZ-PP computational level to show the extent of these effects. The NMR parameters (shielding and nuclear quadrupolar coupling constants) were computed using the relativistic Hamiltonian ZORA and compared to the values obtained with a non-relativistic Hamiltonian. The results show a mixture of the importance of the relativistic corrections as both the size of the halogen atom and the proximity of this atom to the basic site of the Lewis base increase. | Halogens |
A basic developmental framework of the Larix leptolepis Gord male gametophyte is presented in detail by squashing technique. The duration of the meiosis stage was more than 6 months, and included a long diffuse stage during winter. This long duration of the diffuse appearance of the diplotene stage makes L. leptolepis a unique suitable experimental material for studying the structure and function of the diffuse stage of meiosis. In particular, the processes of desynapsing and unpairing, which so far have received little attention, can be examined in detail. In L. leptolepis, the chromosomes undergo a dramatic structural reorganization during the diffuse diplotene stage. Based on the clearly visible differences in chromosome morphology, the diffuse diplotene stage was divided into four periods with suggested nomenclature as follows: schizonema, pre-diffuse diplotene, diffuse diplotene and post-diffuse diplotene. Both simultaneous and successive microsporogenesis were observed within L. leptolepis, and there was no strict relationship between the microsporogenesis types and the tetrad configurations, which are strongly influenced by spindle orientation, especially during meiosis II. The mature pollen grain at pollination consists of five cells aligned in an axial row. The prothallial cells cannot be regarded as senescent cells because they remain capable of division. | Pinaceae |
An overview of the neuroleptic malignant syndrome (NMS) is presented. Its clinical manifestations, pathogenesis, and current treatment are discussed. An increased appreciation of the syndrome may result in more timely interventions and reduce morbidity and mortality in this disorder." | Neuroleptic Malignant Syndrome |
A survey of literature on experimental infections with the liver fluke, Fasciola hepatica published between 2005 and 2009 has revealed a general lack of information on where fluke material (i.e. metacercariae) was sourced from. Even less information was given on the drug status of the fluke isolate used, which is a particular concern for those studies that involved anthelmintics. In these two respects, information on the liver fluke lags far behind that for nematodes, where such information is given almost as a matter of course. Of additional concern is that, at times, information about the source and drug history of fluke isolates was incorrect. The overall aim of the review is to demonstrate why it is important to provide as much information as possible on what fluke material is being used. It also attempts to correct some of the errors in the literature and gather together what information is available about the provenance of those isolates that have been used in recent experimental studies. | Fasciolidae |
For the first time the occurrence of corpuscles of Vater-Pacini lacated in the hili of lymph nodes in patients with melanoma is described. As these corpuscles are pressure sensitive they participate in the regulation of blood and lymph flow inside the lymph node. By these means they may influence secondary deposition of melanoma cells. | Golgi-Mazzoni Corpuscles |
A methodology has been developed for the complete compositional characterization of lithium titanate (LTO) using neutron activation, which is quite challenging and no literature report is available so far. The concept of thermal neutron induced in-situ chain reactions (6)Li(n,alpha)(3)H and (16)O((3)H,n)(18)F has been used for the determination of Li and O through the measurement of (18)F activity. The method is capable of analyzing Li and O in percentage level as reported in the present analysis of two types of lithium titanate samples. Spectroscopic interference of the elements which can directly or indirectly affect the outcome, were evaluated meticulously. Determination of Ti was carried out using fast neutron activation through the product isotopes like (47)Sc, (48)Sc, generated via (n,p) nuclear reactions. Fast neutron activation methodology seems to be advantageous for Ti determination over thermal neutron activation, as it offers self validation through different isotopes and multiple gamma lines. | Nucleons |
Breast cancer, specifically mammary carcinoma, is the most common cause of death from cancer in women worldwide, with a lifetime risk of one in nine, and its prevalence is increasing. It represents around 30% of all cancer in females and approximately 40,000 deaths in the United States per year. Important advances have been made in detection and treatment, but a significant number of breast cancers are still detected late. This summary of its epidemiology and history, the molecular aspects of detection and the main implicated genes emphasizes the etiology and heterogeneity of the disease. It is still not clear whether the remaining cases of breast cancer negative to BRCA are due to mutations in another high penetrance gene or to unknown factors yet to be discovered. | Genes, Recessive |
OBJECTIVE: To discuss indications and therapeutic effects of concomitant surgery for stress urinary incontinence (SUI) and pelvic organ prolapse (POP) through a retrospective clinical review. METHOD: A retrospective review of the data of 16 women undergoing concomitant surgery for SUI and POP was available for analysis. In these cases, 12 patients presented with SUI symptoms associated with moderate or severe anterior vaginal wall prolapse; 4 patients had moderate or severe uterine prolapse associated with dysuria. All cases were confirmed to have type II stress urinary incontinence by preoperative physical examination, urodynamic study and cystography. The surgical procedures for pelvic floor repair included the placement of Gynemesh mesh implant, anterior or total Prolift mesh implant. The tension-free vaginal tape (TVT) or transvaginal tension free vaginal tape-obturator (TVT-O) was used for the anti-incontinence procedure. During the concurrent surgical procedures, pelvic floor repair was performed first. RESULTS: Followed up from 6 to 30 months, all cases got satisfactory results. After the procedure, the patients achieved complete continence without occurrence of dysuria or recurrence of POP. CONCLUSIONS: Stress incontinence and pelvic organ prolapse share common pathophysiologic etiologies and often coexist with one another. In SUI patients with symptomatic or moderate to severe POP, concurrent POP surgery should be performed actively at the time of incontinence surgery to prevent POP exacerbation and the occurrence of dysuria; while in patients with sole POP, occult SUI should be considered, and concomitant prophylactic incontinence measures should be taken at the time of POP repair to prevent the postoperative unmasking of SUI. | Visceral Prolapse |
BACKGROUND: A fundamental step in evolution was the transition from unicellular to differentiated, multicellular organisms. Volvocine algae have been used for several decades as a model lineage to investigate the evolutionary aspects of multicellularity and cellular differentiation. There are two well-studied volvocine species, a unicellular alga (Chlamydomonas reinhardtii) and a multicellular alga with differentiated cell types (Volvox carteri). Species with intermediate characteristics also exist, which blur the boundaries between unicellularity and differentiated multicellularity. These species include the globular alga Eudorina elegans, which is composed of 16-32 cells. However, detailed molecular analyses of E. elegans require genetic manipulation. Unfortunately, genetic engineering has not yet been established for Eudorina, and only limited DNA and/or protein sequence information is available. RESULTS: Here, we describe the stable nuclear transformation of E. elegans by particle bombardment using both a chimeric selectable marker and reporter genes from different heterologous sources. Transgenic algae resistant to paromomycin were achieved using the aminoglycoside 3'-phosphotransferase VIII (aphVIII) gene of Streptomyces rimosus, an actinobacterium, under the control of an artificial promoter consisting of two V. carteri promoters in tandem. Transformants exhibited an increase in resistance to paromomycin by up to 333-fold. Co-transformation with non-selectable plasmids was achieved with a rate of 50 - 100%. The luciferase (gluc) gene from the marine copepod Gaussia princeps, which previously was engineered to match the codon usage of C. reinhardtii, was used as a reporter gene. The expression of gluc was mediated by promoters from C. reinhardtii and V. carteri. Heterologous heat shock promoters induced an increase in luciferase activity (up to 600-fold) at elevated temperatures. Long-term stability and both constitutive and inducible expression of the co-bombarded gluc gene was demonstrated by transcription analysis and bioluminescence assays. CONCLUSIONS: Heterologous flanking sequences, including promoters, work in E. elegans and permit both constitutive and inducible expression of heterologous genes. Stable nuclear transformation of E. elegans is now routine. Thus, we show that genetic engineering of a species is possible even without the resources of endogenous genes and promoters. | Kanamycin Kinase |
A GLC method is presented for the quantitative determination of menthol, phenol, benzocaine, and pyrilamine maleate. The propellent was exhausted from a pressurized can, and an aliquot of the alcoholic base was weighed. After the addition of the internal standard diluted with chloroform, 1 microliter of the mixture was injected in the chromatograph with a flame-ionization detector and a glass column packed with 2.5% OV-225. Average recoveries were 100.3 +/- 1.4, 100.0 +/- 1.4, 101.3 +/- 1.5, and 101.5 +/- 1.5% for menthol, phenol, benzocaine, and pyrilamine maleate, respectively. | Pyrilamine |
Prandial glucose regulation represents a new concept in the management of type 2 diabetes: targeting postprandial glycaemic excursions as a means of achieving long-term glycaemic control. Although control of the overall glycaemic load is the most important factor for the success of long-term management of type 2 diabetes, control of postprandial hyperglycaemia also has positive implications for preventing the development of diabetic complications. Repaglinide is the first prandial glucose regulator to become available in the clinical setting. It has a rapid and short-lived insulinotropic action and can therefore reduce postprandial glucose excursions without increasing the risk of hypoglycaemia. Short-term clinical studies showed that repaglinide is superior to glibenclamide in improving postprandial glycaemic control. Longer-term studies confirmed that improved PGR is accompanied by improved overall glycaemic control that is at least equivalent to that achieved by sulphonylurea treatment. Moreover, because repaglinide can be used with flexible meal patterns without compromising glucose control, it can improve quality of life as indicated by overall treatment satisfaction, well-being and health status. Repaglinide has few contraindications or drug interactions and can be used in a wide range of patients. Although careful titration of repaglinide dose is recommended for patients with mild to moderate renal impairment, no dosage adjustment is otherwise needed in the elderly. In addition to being an effective first-line hypoglycaemic agent, repaglinide is highly effective in combination therapy for patients with type 2 diabetes who require more intensive treatment. When glucose targets are not met using repaglinide monotherapy, the combination of repaglinide with metformin can further improve glycaemic control by enhancing insulin secretion and improving insulin sensitivity. Similarly, when required combination of repaglinide with troglitazone or NPH-insulin can produce better glycaemic control than monotherapy alone. Given that most patients with type 2 diabetes require a multitherapy approach to achieve and sustain adequate glycaemic control, repaglinide will be an important element in future intensive therapy regimens. | Carbamates |
Plasma membrane derived glycosphingolipids (GSLs) destined for digestion are internalized through the endocytic pathway and delivered to the lysosomes. There, GSLs are degraded by the action of exohydrolases, which are supported, in the case of GSLs with short oligosaccharide chains, by sphingolipid activator proteins (SAPs). Four of the SAPs, SAP-A to -D (also called saposins) are synthesized from a single precursor protein (pSAP). Intracellular routing of pSAP and of the GM2 activator protein is only in part dependent on mannose-6-phosphate residues. Their endocytosis occurs in a carbohydrate-independent manner. The inherited deficiencies of individual activators, the GM2 activator, SAP-B, and SAP-C, as well as the deficiency of the precursor pSAP give rise to different, neuronal, white matter or visceral sphingolipid storage diseases. The analysis of cultured fibroblasts from corresponding patients suggests a new model for the topology of endocytosis and lysosomal digestion. It supports the hypothesis that endocytosis of plasma membrane-derived lipids occurs via small intraendosomal and intralysosomal vesicles and membrane structures, that are then digested within the lysosomes. In combined activator protein deficient cells nondegradable GSLs on the surface of intralysosomal vesicles protect them against lysosomal digestion. Mice with disrupted genes for activator proteins (SAP precursor -/-, GM2A -/-) as well as disrupted genes for ganglioside GM2 degrading hexosaminidases (HEXA -/-, HEXB -/-) turned out to be useful models for known human diseases whereas double knock out mice (HEXA -/- and HEXB -/-) show a new phenotype of both mucopolysaccharidosis and gangliosidosis." | Sphingolipid Activator Proteins |
Elucidation of the load-bearing mechanism of the nucleus pulposus (NP) facilitates understanding of the mechanical and metabolic functioning of the intervertebral disc and provides key data for mathematical models. Negatively charged proteoglycans in the NP generate an ionic osmotic pressure, pi(i), which contributes to the tissue's resistance to load and, moreover, is the main mechanism by which the unloaded disc rehydrates. Functionally important, pi(i) has seldom been investigated in situ and, crucially, its variation with strain has not been reported. In a confined compression apparatus, we aimed to apportion the strain-dependent load-bearing mechanism of the NP at equilibrium to the tissue matrix and ionic osmotic pressure; and to determine whether any proteoglycan loss occurs during confined compression testing. Forty-eight confined compression experiments were conducted in isotonic (0.15M NaCl) and hypertonic (3.0 and 6.1M NaCl) external solutions in single and multiple step-strain protocols. The 6.1M NaCl external solution was needed to eliminate as much of the ionic effects as possible. The ionic osmotic pressure was well described by pi(i)=19.1lambda(-1.58) (R(2)=0.992), and was approximately 70% of the applied load at equilibrium, independent of lambda. The effective aggregate modulus, H(A)(eff), also increased with strain: H(A)(eff)=59.0lambda(-2.18). Concentrations of sulphated glycosaminoglycans were obtained for the samples tested in isotonic NaCl with no proteoglycan loss detected from the confined compression tests. These results highlight the non-linearity of the stress-strain response of NP tissue and the necessity to include a non-linear function for osmotic pressure in mathematical models of this tissue. | Osmotic Pressure |
OBJECTIVE: To investigate transcranial transmission (TT) and the dampening effect of the skin in patients and cadaver heads. DESIGN: In patients a pure tone bone conduction audiogram for ipsilateral and contralateral stimulation was performed. The TT was defined as the difference between ipsilateral and contralateral hearing thresholds. In cadaver heads ipsilateral and contralateral promontory motion was measured using a three-dimensional Laser Doppler Vibrometer system. STUDY SAMPLE: Seven single-sided deaf patients fitted with a Baha((R)) Connect, fifteen single-sided deaf patients without a bone conduction hearing aid and five Thiel-embalmed cadaver heads were included. RESULTS: The TT decreased with increasing frequency in patients and cadaver heads. No significant difference was seen between patients and cadaver heads. Measurements on patients and cadaver heads showed increasing skin attenuation with increasing frequency. However, the dampening effect was 3-12 dB higher in patients than in cadavers at all frequencies. CONCLUSION: The TT was not significantly different for patients compared to cadaver heads. The value of promontory motion to estimate TT in patients need to be further evaluated. The skin attenuates a BC stimulus by 10-20 dB in patients and by a smaller amount in cadaver heads, probably due to changes in the properties of the Thiel-conserved skin. | Bone Conduction |
The technique of transcervical catheterization for artificial insemination has gained practical importance over the last 3 and 1 decades in bitches and queens, respectively. The vagina of both species has a thickening of the dorsal aspect called dorsal medial fold, which restricts the lumen of the paracervix, making catheterization of the cervix difficult both with manual and endoscopic techniques. Manual catheters have been used initially in the bitch and are now gradually being replaced by rigid endoscopy through the adaptation of human cystoscopes and ureteroscopes. Cystoscopes provide excellent imaging of the vagina, but cervical catheterization is more difficult due to the oblique 30 degrees viewing angle of its telescope and may not be long enough to catheterize large size bitches. Ureteroscopes allow an acceptable view of the vaginal mucosa and offer advantages such as the possibility to catheterize the cervix of bitches of all body sizes, manipulate the cervical tubercle when the external cervical os is not visible, offer a better visualization of the cervix using the shunt (a large Foley catheter which allows insufflation and distention of the vagina). Feline cervical catheterization has been achieved with three different types of catheters; the last one, developed following careful anatomical studies of how the feline vaginal lumen changes during estrus, allows cervical catheterization thanks to digital manipulation of the cervix through the rectum. | Insemination, Artificial |
Aim: Nivolumab is an immune checkpoint inhibitor that has recently been widely used for metastatic malignant melanoma. We report a case who developed multiple different ocular immune-related side effects (iRAEs) related to nivolumab.Case Presentation: A 60-year-old man on nivolumab treatment for metastatic malignant melanoma developed a decrease in vision in both eyes several days after the third infusion. The initial best-corrected visual acuity (BCVA) was counting fingers in both eyes. Slit-lamp examination revealed no abnormal findings in the anterior segment of both eyes. Posterior segment evaluation showed serous retinal detachment, including the whole macula and inferior retina in both eyes, and optical coherence tomography (OCT) confirmed the diagnosis. On en face OCT analysis, hyperautoflorescent dots were noticed on the whole macular region but more intense at the inferior quadrant corresponding to serous retinal detachment. On Fluorescein Angiography (FA), no abnormality was observed. Oral corticosteroid treatment was administered. Subretinal fluid resolved one week after treatment in the right eye and two weeks after treatment in the left eye. BCVA was 20/20 in both eyes at first month of treatment. After that, oral corticosteroid treatment was tapered and stopped at the end of the second month. The patient was followed monthly. Two months after the treatment patient presented with an anterior uveitis episode with mild vision loss. Slit-lamp examination revealed 3+ cells in the anterior chamber and posterior synechia in both eyes. Posterior segment examination was normal. The patient was treated with topical corticosteroid and cycloplegic for two months. Hyperautoflorescent dots formed with serous detachment disappeared six months after the onset of serous detachment, and they did not occur during anterior uveitis episodes.Conclusions: This is the first clinical report of nivolumab-associated ocular iRAEs presenting with recurrent episodes presenting with serous retinal detachment and anterior uveitis. En face OCT imaging may help diagnose and show the activity of the posterior segment manifestation. When managed properly and observed closely following general and ocular conditions, it is possible to held iRAEs and overcome them by oral and/or topical corticosteroid therapy without interrupting the nivolumab. | Uveitis, Anterior |
Melphalan significantly contributes to the increase in childhood cancer survival rate. It acts as a gonadotoxic agent and leads to testes damage, dysbalance in gonadal hormones, and impairment in the germ cell proliferation. Therefore, it might be a potent threat to male fertility in individuals who have undergone melphalan treatment during childhood cancer. However, the molecular mechanisms of melphalan-induced gonadal damage are not yet fully explored and they need to be investigated to determine the benefit-risk profile. In the present study, juvenile male SD rats were subjected to single and intermittent cycles of melphalan exposure in a dose-dependent (0.375, 0.75 and 1.5 mg/kg) manner. Methods of end-points evaluations were quantification of micronuclei formation in peripheral blood, sperm count, sperm motility and head morphology, sperm and testicular DNA damage, histological studies in testes, oxidative/nitrosative stress parameters. A single cycle of exposure at high dose (1.5 mg/kg) produced significant effect on micronuclei formation only after the first week of exposure, whereas failed to produce significant effect at the end of the sixth week. Intermittent cycles of exposure at the dose of 1.5 mg/kg produced significant alterations in all the parameters (micronuclei in peripheral blood, testes and epididymides weight and length, MDA, GSH and nitrite levels, sperm count and motility, sperm head morphology, testicular and sperm DNA damage, protein expression in testes and histological parameters). So, time of exposure as well as the amount of exposure (total dosage administered) is critical in determining the magnitude of the damage in germ cell risk assessment. | Melphalan |
Although any peripheral nerve may be compressed anywhere along its course, nerve compression syndromes typically occur at predictable sites with predictable clinical presentations. A detailed history and physical examination can establish a diagnosis, and electrodiagnostic studies and at times imaging can confirm it. Physicians should adopt a systematic approach of diagnosing and treating these types of nerve lesions. The physician and the patient can be rewarded with favorable outcomes. | Nerve Compression Syndromes |
BACKGROUND: It remains unclear whether adults with metabolically healthy obesity (MHO) have altered myocardial tissue-level characteristics. OBJECTIVES: This study aims to assess the subclinical myocardial tissue-level characteristics of adults with MHO. METHODS: The EARLY-MYO-OBESITY (EARLY Assessment of MYOcardial Tissue Characteristics in OBESITY; NCT05277779) registry was a prospective, 3-center, cardiac imaging study of obese nondiabetic individuals without cardiac symptoms who underwent cardiac magnetic resonance. Myocardial tissue-level characteristics, including extracellular volume fraction (ECV) and native T2 values, were measured as indicators of myocardial fibrosis and edema. Global longitudinal peak systolic strain and early diastolic longitudinal strain rate were assessed by tissue tracking analysis to detect subclinical systolic and diastolic dysfunction. RESULTS: A total of 120 participants were included: MHO (n = 32; mean age, 38 years; 41% men), metabolically healthy controls without obesity (n = 32; mean age: 37 years; 41% men), and metabolically unhealthy obesity (MUHO) (n = 56; mean age: 37 years; 55% men). The MHO group had higher ECV and native T2 values than healthy controls (both P < 0.001); furthermore, the ECV was higher in the MUHO group than in the MHO group (P = 0.002). The prevalence of myocardial fibrosis was 44% (14 of 32) in the MHO group and 71% (40 of 56) in the MUHO group. Although there was no intergroup difference in left ventricular ejection fraction, the MHO group had reduced global longitudinal peak systolic and early diastolic longitudinal strain rates, indicating subclinical systolic and diastolic dysfunction. Multivariate regression analysis identified increased body mass index to be an independent risk factor for myocardial fibrosis (OR: 6.28 [95% CI: 3.17-12.47]; P < 0.001). CONCLUSIONS: This study provides the first evidence of subclinical myocardial tissue-level remodeling in adults with obesity, regardless of metabolic health. Early identification of cardiac impairment may facilitate preventive strategies against heart failure in the MHO population. (EARLY Assessment of MYOcardial Tissue Characteristics in OBESITY [EARLY-MYO-OBESITY]; NCT05277779). | Obesity, Metabolically Benign |
Georgina Mills discusses how the RCVS is furthering its commitment to inspiring leadership in the profession. | Veterinarians |
Harmaline, harmine, 2-methylharmine and harmolol, members of the harmala family of alkaloids were tested for their action on ouabain-elicited contractions of the guinea-pig ileum. All four alkaloids were found to relax tissue previously contracted by ouabain, but they differed in their potency and reversibility. Harmaline was equipotent with harmine but more easily reversible. 2-Methylharmine and harmolol were found to be less potent and readily reversible. It is evident that the inhibition mediated by harmaline occurs at a site other than that which ouabain binds. Ca-free Tyrode caused relaxation of tissue contracted by ouabain. This effect was partially reversed in the presence of normal Tyrode solution. In presence of high K the response to ouabain was almost abolished. Harmaline inhibited Ca-induced contractions in a non-competitive manner while neither 2-methylharmine nor harmalol had any effect. In the discussion the action of harmala alkaloids is shown to be directly related with CA ion movements. | Harmala Alkaloids |
BACKGROUND: Buprenorphine is under investigation as a pharmacotherapeutic agent for treating opioid dependence in pregnant women. We hypothesized that there would be a relationship between the cumulative maternal dose of buprenorphine during pregnancy and the concentration of buprenorphine and norbuprenorphine in maternal and infant hair. METHODS: This study examined buprenorphine and norbuprenorphine concentrations in hair obtained from 9 buprenorphine-maintained pregnant women and 4 of their infants. Specimens were analyzed by liquid chromatography-tandem mass spectrometry with limits of quantification of 3.0 pg/mg. All maternal hair specimens were washed with methylene chloride before analysis, and when sufficient amounts of maternal hair were available, specimens also were analyzed without washing. Infant hair specimens were not washed. RESULTS: Buprenorphine concentrations were significantly greater in unwashed hair than washed hair (P = 0.031). Norbuprenorphine concentrations were significantly greater than buprenorphine concentrations in both maternal (P = 0.0097) and infant hair (P = 0.0033). There were statistically significant associations between the cumulative maternal dose of buprenorphine administered and the concentrations of buprenorphine (washed, P <0.0001; unwashed, P = 0.0004), norbuprenorphine (washed, P <0.0001; unwashed, P = 0.0005), and buprenorphine plus norbuprenorphine (washed, P <0.0001; unwashed, P = 0.0005) for both washed and unwashed maternal hair specimens. There was a significant positive association between concentrations of buprenorphine and norbuprenorphine in maternal hair (washed, P <0.0001; unwashed, P = 0.0003), a trend for this association in infant hair (P = 0.08), and an association between buprenorphine concentrations in maternal unwashed hair and infant hair (P = 0.0002). The buprenorphine:norbuprenorphine ratio increased in distal segments. CONCLUSION: Buprenorphine treatment during gestation provides an opportunity for monitoring drug disposition in maternal and fetal tissues under controlled conditions. | Buprenorphine |
OBJECTIVES: Oral candidiasis is the most common opportunistic fungal infection of oral mucosa and results from an overgrowth of Candida, especially Candida albicans. The potential anti-C. albicans and cytotoxicity of punicalagin (PCG), isolated from Punica granatum, alone or with nystatin (NYS) were evaluated. METHODS: Activity of compounds alone or in combinations was determined against two C. albicans strains (ATCC 90028 and SC5314). Minimal inhibitory concentration (MIC)-50 and Minimum Fungicidal Concentration (MFC) were assessed by XTT assay and CFU counts, respectively. For combinations, determination of fractional inhibitory concentration index was performed. Ergosterol pathway was investigated as a possible PCG antifungal mechanism. Cytotoxicity assays were undertaken on human primary oral keratinocytes and gingival fibroblasts incubated with antifungal concentrations of PCG and/or NYS for 24 hr. RESULTS: Combination of NYS and PCG increased antifungal efficacy, compared with compounds tested alone. Combinations 4 (PCG-6.25 mug/ml; NYS-3.9 mug/ml) and 5 (PCG-12.5 mug/ml; NYS-1.95 mug/ml) were more effective since they reduced the MIC-50 of PCG (50 mug/ml) by 8 and 4 times, respectively, increased the candidal inhibition and nullified the PCG cytotoxicity for keratinocytes. PCG antifungal mechanism did not involve ergosterol biosynthesis pathway. CONCLUSIONS: The favorable outcomes for combination of PCG and NYS encourage further testing this therapeutic strategy against C. albicans. | Nystatin |
BACKGROUND: While many risk factors for preeclampsia, such as increased body mass index, advanced maternal age, chronic hypertension, diabetes, are now established in clinical practice, maternal lipid profile has not been included in the risk assessment for preeclampsia. We aim to characterize the serum levels of Total Cholesterol (TC), High density lipoprotein (HDL), Low density lipoprotein (LDL), Triglycerides (TG), Apolipoprotein A1, Apolipoprotein B and their ratios TC/HDL and ApoB/ApoA1 in the maternal and fetal circulations of normal pregnancy, preeclampsia (PE), fetal growth restriction (FGR) and PE + FGR. METHODS: A prospective cross-sectional case control study was conducted measuring maternal and fetal lipid levels by enzymatic analysis and immune-turbidimetric enzymatic assays. FGR was defined by elevated umbilical artery Doppler resistance in association with estimated fetal weight < 10%. Kruskal Wallis non-parametric analysis of variance was used to test for homogeneity across the clinical groups for each of the variables, Mann-Whitney tests for pairwise comparisons and Spearman rank correlation were used to quantify gestational age-related changes. RESULTS: (1) TG levels were elevated in maternal PE and cord blood PE + FGR groups compared to normal pregnancies. (2) A statistically significant elevation of fetal ApoB levels was observed in PE, FGR and PE + FGR compared to normal pregnancies. Apolipoprotein levels A1 and B were not different between maternal groups. (3) TC, HDL, LDL and TC/HDL levels did not show any significant gestational variation or between clinical groups in the maternal or fetal circulation. CONCLUSIONS: Elevation in maternal TG levels may have a role in the pathogenesis of PE. The implications of elevated maternal and fetal TG levels and elevated fetal Apolipoprotein B levels deserves further exploration of their role in long term cardiovascular risk in the mother as well as the offspring. | Immunoturbidimetry |
Evaluation of metabolic pathways is one of the challenging areas in biological and pharmaceutical sciences. Phenanthridine oxidation to phenanthridinone is used commonly to study aldehyde oxidase activity. This reaction could pass through phenanthridine N-oxide intermediate. In the present study, the application of multivariate curve resolution, optimized by alternating least squares (MCR-ALS) to investigate this metabolic pathway has been described. The results obtained from MCR-ALS analysis along with those obtained from the use of potassium ferrocyanide method indicated that phenanthridine is directly oxidized to phenanthridinone by rat liver aldehyde oxidase without passing through phenanthridine N-oxide intermediate. It was also found that the later compound is not metabolized by this enzyme. | Phenanthridines |
BACKGROUND: Patients with psychiatric disorders (as well as general medical conditions) often describe their lives in terms of suffering. Although suffering is honored as a central focus of physicians' concerns, it is not even indexed in the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition. Generally connoting severe, prolonged distress, suffering can be distinguished from pain, depression, and anxiety. The aims of this article are to consider whether attending to suffering per se in psychiatric patients merits attention independent of other commonly assessed psychiatric symptoms such as anxiety, depression, and conventional distress, and how targeting suffering per se might add value to psychiatric patient care. METHODS: Sources for this article were obtained via a selective literature search in PubMed using the terms suffering" in the title and the terms "psychiatric disorder," "mental illness," "assessment," "measurement," "scale," "existential suffering," and "unbearable suffering." Articles of interest were followed up using a snowball technique to examine "similar articles" and "cited by" titles to find additional pertinent articles. RESULTS: Definitions of suffering in the medical literature stress its subjectivity, particularity, complexity, and connection to a wide variety of noxious sensations, as well as real and anticipated deficits, losses, and thwarted motivations. These can affect the entire spectrum of universal human needs, from basic biological issues through intrapsychic, interpersonal, and social issues, encompassing existential concerns of meaning, purpose, and transcendence. Based on these factors, a definition of suffering in patients with psychiatric disorders is proposed. Although efforts to measure suffering have been limited and numerous gaps in the literature are evident, several scales may offer suitable bases for the study of suffering in patients with psychiatric disorders. CONCLUSIONS AND IMPLICATIONS: Ascertaining sources of suffering may require new types of inquiry and additional time. Well-described, evidence-informed strategies and time-honored psychotherapy techniques are available for addressing the numerous concerns that contribute to suffering. Patients with psychiatric disorders whose distinct, multidimensional sources of suffering are identified, acknowledged, and addressed may experience better treatment quality, greater treatment satisfaction, and possibly better outcomes than those whose clinicians' attention is limited to conventional psychiatric signs and symptoms." | Mental Disorders |
In 1997, the American Dental Association (ADA) and the American Academy of Orthopaedic Surgeons (AAOS) published an advisory statement regarding antibiotic prophylaxis for patients with total joint replacements undergoing dental treatment. The first periodic update of these guidelines was published in 2003. Nevertheless, confusion exists among dentists and physicians as to the clinical indications for premedication in this patient population. This article serves as an overview of current recommendations for use of chemoprophylaxis in the dental treatment of patients with prosthetic joints." | Dental Care for Chronically Ill |
The special issue Symbiotic Nitrogen Fixation in Legume Nodules: Metabolism and Regulatory Mechanisms" aims to investigate the physiological and biochemical advances in the symbiotic process with an emphasis on nodule establishment, development and functioning. The original research articles included in this issue provide important information regarding novel aspects of nodule metabolism and various regulatory pathways, which could have important future implications. This issue also included one review article that highlights the importance of using legume trees in the production of renewable biofuels." | Root Nodules, Plant |
We report on a 20-year-old man and a 16-year-old woman with a chromosomal imbalance derived from a balanced translocation, t(Y;1)(q12;p36.3) of the father. The man had a partial trisomy for 1p36.3-pter [46,X,der(Y)t(Y:1)(q12;p36.3)] and mild craniosynostosis of metopic and sagittal sutures as well as a borderline mental impairment, while the woman with a deletion for 1p36.3-pter [46,XX,der(1)t(Y;1)(q12;p36.3)] showed dysmorphic face with large anterior fontanel and severe developmental delay. Fluorescence in situ hybridization (FISH) showed that his trisomy spanned the 5.3-Mb region from 1p telomere harboring the critical region for craniosynostosis. To our knowledge, the man is the first case of a pure type of simple 1p36.3 trisomy as the effect of heterochromatic Yq12-qter deletion likely does not affect phenotype. | Aneuploidy |
Recent advances have been made in the cellular and molecular mechanisms involved in monostotic and polyostotic fibrous dysplasia, a rare nonmalignant disease causing bone deformations and fractures. The molecular basis of fibrous dysplasia has been clarified when mutations affecting the stimulatory alpha subunit of G protein (Gs) have been found in dysplastic bone lesions. The histological analysis of dysplastic lesions revealed that the mutations in Gsalpha caused abnormalities in cells of the osteoblastic lineage and therefore in the bone matrix. Further in vitro analyses of bone cells from mutant dysplastic bone lesions revealed that the abnormal deposition of immature bone matrix in fibrous dysplasia results from decreased differentiation and increased proliferation of osteoblastic cells. Finally, the signaling pathway involved in these osteoblastic abnormalities has been identified. It is now apparent that the constitutive elevation in cAMP level induced by the Gsalpha mutations leads to alterations in the expression of several target genes whose promoters contain cAMP-responsive elements, such as c-fos, c-jun, Il-6 and Il-11. This in turn affects the transcription and expression of downstream genes and results in the alterations of osteoblast recruitment and function in dysplastic bone lesions. These mechanisms provide a cellular and molecular basis for the alterations in bone cells and bone matrix in fibrous dysplasia." | Fibrous Dysplasia, Polyostotic |
BACKGROUND AND AIMS: The platelet inhibitor aspirin reduces inflammation and atherosclerosis in both apolipoprotein E deficient (apoE(-/-)) mice and low-density lipoprotein receptor deficient (Ldlr(-/-)) mice. Similarly, the factor Xa inhibitor rivaroxaban reduces atherosclerosis in both apoE(-/-) and Ldlr(-/-) mice. We tested the hypothesis that the combination of aspirin and rivaroxaban reduces atherosclerosis in mice to a greater extent than either agent alone. METHODS: Male Ldlr(-/-) mice were fed a western-type diet for 12 weeks to induce atherosclerosis. Cohorts of mice received aspirin in the water and/or rivaroxaban in the diet. Atherosclerosis and lesion composition were measured in the aortic sinus and the aorta. Expression of 55 proteins in the aorta and plasma was determined using multiplex ELISA assays. RESULTS: Aspirin alone, rivaroxaban alone, and the combination of both agents significantly reduced atherosclerosis in the Ldlr(-/-) mice compared with control Ldlr(-/-) mice fed a western-type diet. However, there were no significant differences in atherosclerosis in the group receiving aspirin and rivaroxaban compared with the groups that received aspirin or rivaroxaban alone. Aspirin, rivaroxaban and the combination reduced macrophage content and apoptosis in the lesions compared with controls but there was no difference between the three treatment groups. We observed statistically significant changes in the expression of a small number of proteins in the aorta and plasma in mice treated with aspirin and/or rivaroxaban. CONCLUSIONS: Contrary to our expectation, the combination of aspirin and rivaroxaban did not further reduce atherosclerosis in Ldlr(-/-) mice beyond the level observed with each agent alone. | Rivaroxaban |
The tearing eye (epiphora) is deemed to be the leading symptome of efferent tear duct stenosis. Nevertheless, epiphora might be caused by ocular surface pathologies or even intraocular diseases. A distinguished anamnesis and sufficient clinical examination is most meaningful for the differential diagnostic distinction. Therapy is based on pathologic changes. In case of ocular surface disease, a suitable tear substitution and antiinflammatory approach is mandatory. Multifarious triggers have to be considered as well. Addressing tear film distribution, suitable oculoplastic surgery is required. Efferent tear duct stenosis necessitates surgical treatment as the level of suffering is often very high and acute exacerbations may develop. Besides recanalization, anastomosing techniques represent the available therapeutic principles. Possible surgical approaches offer a great variety and many influencing factors navigate therapy decisions. This part of the review comments on the most important therapeutic approaches for lacrimal apparatus diseases. | Lacrimal Apparatus Diseases |
We evaluated the protective effects of Gentiana lutea extracts (GLEx) and 6-Gingerol (6-G) on clastogenicity of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and 7,12-dimethylbenz(alpha) anthracene (DMBA) in vitro on HepG2 cells using the frequencies of induced micronuclei (MN) as the end point. Pre-, post- and simultaneous treatments with GLEx or 6-G and the carcinogens were carried out. Both GLEx post- and simultaneous treatments reduced the frequencies of MN induced by MNNG and DMBA. Probably this effect is due to an increase of cytostasis and a physico-chemical interaction between GLEx and DMBA under simultaneous treatment. Pre- and simultaneous treatments with 6-G significantly reduced the yield of MNNG-induced micronuclei without affecting % of cytostasis. Simultaneous treatment with 6-G plus DMBA resulted in reduction in the frequency of MN and an increase in cytotoxicity compared to sample treated alone with DMBA, whereas a post-treatment, caused a significant decrease in the yield of MN compared with DMBA alone without any cytotoxic effect. These results are compared with our earlier data obtained in the same system with other phytochemicals. It is concluded that for a critical evaluation of the protective effects of phytochemicals, both the influence on the induced MN and induced cytostasis have to be considered." | Micronuclei, Chromosome-Defective |
OBJECTIVE: To examine the association of viruses with acute febrile respiratory disease in horses. Design Nasal swab and serum samples were collected from 20 horses with acute febrile upper respiratory disease that was clinically assessed to have a viral origin. METHODS: Each of the samples was inoculated onto equine fetal kidney, RK13 and Vero cell cultures, and viral nucleic acid was extracted for polymerase chain reaction (PCR) or reverse transcription PCR. PCR primers were designed to amplify nucleic acid from viruses known to cause or be associated with acute febrile respiratory disease in horses in Australia. A type specific ELISA was used to measure equine herpesvirus (EHV1 and EHV4) antibody, and serum neutralisation assays were used to measure equine rhinitis A virus (ERAV) and equine rhinitis B virus 1 and 2 (ERBV1 and ERBV2) antibody titres in serum samples. RESULTS: Virus was isolated from 4 of 20 nasal swab samples. There were three isolations of EHV4 and one of ERBV2. By PCR, virus was identified in the nasal swab samples of 12 of the 20 horses. Of the 12 horses [corrected] that were positive, 17 viruses were detected as follows: there was [corrected] one triple positive (EHV4, EHV2, and EHV5), three double positives (EHV4, ERBV and EHV5, ERBV (2 horses)) and 8 [corrected] single positives (EHV4 (2 horses), EHV5 (3 horses) and ERBV (3 [corrected] horses). CONCLUSION: By virus isolation and PCR, 17 viruses were identified in nasal swab samples from 12 of 20 horses that had acute febrile respiratory disease consistent with a diagnosis of virus infection. Initial PCR identification and subsequent virus isolation led to the isolation of ERBV2 for the first time in Australia and the second time anywhere of ERBV2. | Erbovirus |
Objectives: Hot flashes are unpleasant long-term complications of breast cancer. This study aimed to evaluate the effects of a traditional Persian medicine containing extracts of Cichorium intybus L. (chicory) and Fumaria parviflora L. (Fumitory) extract syrup (CFS) compared with placebo when used as intended. Design: Randomized, double-blind, placebo-controlled clinical trial. Setting/Location: The Oncology Ward of Shahid Modarres Hospital (Tehran, Iran). Subjects: Breast cancer survivors undergoing hormone deprivation therapy. Interventions: Patients were randomly allocated to receive 5 mL CFS or placebo syrup three times a day, for 4 weeks. Outcome measures: The co-primary outcomes were self-reported daily hot flashes frequency and severity scores assessed using self-reported daily dairies, including 1 week of baseline data. Results: Of the 148 patients screened, 137 were eligible, and 96 were randomly allocated to receive either CFS (n = 48) or placebo (n = 48). All participants who returned their dairies were compliant and analyzed as randomized in the a priori per-protocol analysis. After 4 weeks of treatment, both the mean daily hot flashes frequency and severity score had reduced by 57% in the CFS group and 10% in the placebo group. The overall weekly mean daily hot flashes frequency (effect size eta(p)(2) 0.221, p < 0.001, n = 66) and severity scores (effect size eta(p)(2) 0.160, p = 0.001, n = 66) were significantly lower in the CFS group compared with the placebo group (one-within one-between repeated-measures analysis of variance adjusted for baseline). CFS was well tolerated, with similar proportions of serious and nonserious adverse events occurring in both groups. Conclusions: This is the first study to report the effects of chicory or fumitory for the treatment of hot flashes. The findings provide preliminary evidence that CFS can improve hot flashes in breast cancer survivors undergoing hormone deprivation therapy. More research is warranted to confirm its effectiveness, safety, and mechanisms of action. Clinical Trial Registration: IRCT20210226050506N1. | Fumaria |
Oxytocin is a highly successful and safe agent for inducing labor and has a fairly large therapeutic index. It has, however, minimal, but not trivial, antidiuretic and vascular activity when used in large doses. Therefore, to induce labor, low-dose oxytocin dosing regimens that produce efficacious uterine activity and avoid side effects are recommended. Oxytocin should be used in the lowest possible doses necessary to effect a clinical response. Diligence must be exercised when monitoring labor and fetal well-being. Hofbauer, the first to use oxytocin to induce labor, said in 1927 that oxytocin, with its power of producing regular, rhythmical and forcible uterine contractions, should be regarded as a most beneficent and valuable agent, which, however, should always be employed with care and a realisation of its limitations and dangers." His words remain valid today." | Oxytocics |
Although most unicellular organisms reproduce asexually, most multicellular eukaryotes are obligately sexual. This implies that there are strong barriers that prevent the origin or maintenance of asexuality arising from an obligately sexual ancestor. By studying rare asexual animal species we can gain a better understanding of the circumstances that facilitate their evolution from a sexual ancestor. Of the known asexual animal species, many originated by hybridization between two ancestral sexual species. The balance hypothesis predicts that genetic incompatibilities between the divergent genomes in hybrids can modify meiosis and facilitate asexual reproduction, but there are few instances where this has been shown. Here we report that hybridizing two sexual Caenorhabditis nematode species (C. nouraguensis females and C. becei males) alters the normal inheritance of the maternal and paternal genomes during the formation of hybrid zygotes. Most offspring of this interspecies cross die during embryogenesis, exhibiting inheritance of a diploid C. nouraguensis maternal genome and incomplete inheritance of C. becei paternal DNA. However, a small fraction of offspring develop into viable adults that can be either fertile or sterile. Fertile offspring are produced asexually by sperm-dependent parthenogenesis (also called gynogenesis or pseudogamy); these progeny inherit a diploid maternal genome but fail to inherit a paternal genome. Sterile offspring are hybrids that inherit both a diploid maternal genome and a haploid paternal genome. Whole-genome sequencing of individual viable worms shows that diploid maternal inheritance in both fertile and sterile offspring results from an altered meiosis in C. nouraguensis oocytes and the inheritance of two randomly selected homologous chromatids. We hypothesize that hybrid incompatibility between C. nouraguensis and C. becei modifies maternal and paternal genome inheritance and indirectly induces gynogenetic reproduction. This system can be used to dissect the molecular mechanisms by which hybrid incompatibilities can facilitate the emergence of asexual reproduction. | Caenorhabditis |
Intravaginal foreign bodies of long duration are a rare entity and are seen in the practice of Obstetrics and Gynaecology, but patients may present to the Accident and Emergency department for their removal. Various bizarre objects have been inserted into the vagina and many patients are too embarrassed and will wait and try to remove them themselves rather than seek medical advice. Vaginal foreign bodies of long duration may be complicated by fistulas and such patients should be referred to the gynaecologist. | Rectovaginal Fistula |
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