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LEARNING OBJECTIVES: After studying this article, the participant should be able to: 1. Recognize facial muscle contraction direction and muscle morphology based on skin surface movements and facial rhytides. 2. Classify different muscle contraction patterns and target respectively with the recommended dosage and injection technique. 3. Apply the presented injection techniques to the patients' individual anatomy with greater precision and without affecting adjacent muscles or causing other adverse events. SUMMARY: Facial muscular anatomy has recently gained increased attention, with new investigative methodologies and new injection techniques arising on the market. These recent advancements have increased our understanding about the functional anatomy of facial muscles and have changed the way health care professionals see and understand their interplay during various facial expressions and in determining facial shape. This new anatomical understanding of facial muscles and their interaction has resulted in superior neuromodulator treatment outcomes with fewer side effects and with increased precision. The latter is of greatest importance, as all facial muscles act as a unit and connect with each other. It is therefore paramount to target during neuromodulator treatments only the muscle responsible for the aesthetic effect desired and not other adjacent muscles, which can have different or even antagonistic effects. Conventional anatomy was previously limited to two-dimensional explanations of muscle locations without incorporating their detailed action or their three-dimensional location of extent. The new" anatomy incorporates those novel concepts and, once understood, will help health care providers to understand better and to "read" the underlying muscular anatomy based on the wrinkle status and based on the change in skin surface landmarks based on the actions of the underlying musculature. The following article summarizes tips and tricks, pearls and pitfalls, and dos and don'ts during facial neuromodulator injections along with a guide toward adverse event management and patient outcome assessment with special focus on the underlying anatomy." | Facial Muscles |
Sweet cherry production faces new challenges that necessitate the exploitation of genetic resources such as varietal collections and landraces in breeding programs. A harmonized approach to characterization is key for an optimal utilization of germplasm in breeding. This study reports the genotyping of 63 sweet cherry accessions using a harmonized set of 11 simple sequence repeat (SSR) markers optimized in two multiplexed PCR reactions. Thirty-eight distinct allelic profiles were identified. The set of SSR markers chosen proved highly informative in these germplasm; an average of 6.3 alleles per locus, a PIC value of 0.59 and above-average expected and observed heterozygosity levels were detected. Additionally, 223 amplified fragment length polymorphism (AFLP) markers derived from eight selective primer combinations were employed to further differentiate 17 closely related accessions, confirming the SSR analysis. Genetic relationships between internationally known old cultivars were revealed: SSR fingerprints of Schneiders Spate Knorpelkirsche" and "Germersdorfer" were found to be identical to those of the standard cultivar "Noire de Meched", among others, whereas four accessions known as "Hedelfinger Riesenkirsche" and four known as "Grosse Schwarze Knorpelkirsche" showed allelic differences at various loci. The genetic diversity of locally-grown cultivars worldwide might be currently underestimated. Several autochthonous Austrian sweet cherry germplasm accessions were genotyped for the first time and their genetic relationships analyzed and discussed. Interestingly, seven Austrian sweet cherry landraces were shown to be clearly genetically separated from international and modern varieties, indicating that Austrian germplasm could include valuable genetic resources for future breeding efforts." | Prunus avium |
Tea, after water, is the most frequently consumed beverage in the world. The fermentation of tea leaves has a pivotal role in its quality and is usually monitored using the laboratory analytical instruments and olfactory perception of tea tasters. Developing electronic sensing platforms (ESPs), in terms of an electronic nose (e-nose), electronic tongue (e-tongue), and electronic eye (e-eye) equipped with progressive data processing algorithms, not only can accurately accelerate the consumer-based sensory quality assessment of tea, but also can define new standards for this bioactive product, to meet worldwide market demand. Using the complex data sets from electronic signals integrated with multivariate statistics can, thus, contribute to quality prediction and discrimination. The latest achievements and available solutions, to solve future problems and for easy and accurate real-time analysis of the sensory-chemical properties of tea and its products, are reviewed using bio-mimicking ESPs. These advanced sensing technologies, which measure the aroma, taste, and color profiles and input the data into mathematical classification algorithms, can discriminate different teas based on their price, geographical origins, harvest, fermentation, storage times, quality grades, and adulteration ratio. Although voltammetric and fluorescent sensor arrays are emerging for designing e-tongue systems, potentiometric electrodes are more often employed to monitor the taste profiles of tea. The use of a feature-level fusion strategy can significantly improve the efficiency and accuracy of prediction models, accompanied by the pattern recognition associations between the sensory properties and biochemical profiles of tea. | Electronic Nose |
The transcription factor NF-kappaB is a key regulator of hundreds of genes involved in cell survival and inflammation. There is ample evidence that NF-kappaB is activated in cerebral ischemia, mainly in neurons. Despite its well known role as an antiapoptotic factor, in cerebral ischemia NF-kappaB contributes to neuronal cell death, at least if the ischemia is severe enough to lead to irreversible brain damage. In contrast, NF-kappaB also seems to be responsible for the preconditioning effect of a transient and sublethal ischemia, perhaps by dampening its own subsequent full activation. Among the five NF-kappaB subunits, RelA and p50 are responsible for the detrimental effect in cerebral ischemia. Activation of NF-kappaB signaling is mediated by the upstream kinase inhibitor of kappaB kinase and is triggered by hypoxia, reactive oxygen species, and several inflammatory mediators. Interestingly, the complex NF-kappaB signaling pathway provides drug targets at several levels. Modulation of NF-kappaB signaling has the potential to interrupt multiple inflammatory and apoptotic mechanisms through one specific molecular target. | NF-kappa B p50 Subunit |
This paper reports two cases of successfully treated patients suffering from a rare entity, the catastrophic anti-phospholipid syndrome (CAPS). Management of those patients is discussed at the light of existing literature. | Antiphospholipid Syndrome |
The pudendal nerve entrapment is an entity understudied by diagnosis imaging. Various causes are recognized in relation to difficult labors, rectal, perineal, urological and gynecological surgery, pelvic trauma fracture, bones tumors and compression by tumors or pelvic pseudotumors. Pudendal neuropathy should be clinically suspected, and confirmed by different methods such as electrofisiological testing: evoked potentials, terminal motor latency test and electromyogram, neuronal block and magnetic resonance imaging. The radiologist should be acquainted with the complex anatomy of the pelvic floor, particularly on the path of pudendal nerve studied by magnetic resonance imaging. High resolution magnetic resonance neurography should be used as a complementary diagnostic study along with clinical and electrophysiological examinations in patients with suspected pudendal nerve neuralgia. | Pudendal Neuralgia |
ETHNOPHARMACOLOGICAL RELEVANCE: Detoxifying and blood-activating Chinese medicine granule formula, which includes 15 g of Polygonum cuspidatum Sieb. et Zucc. (Polygonum cuspidatum) and 10 g of Crataegus pinnatifida Bunge (Hawthorn), can relieve the symptoms and serve as supplementary treatment for unstable angina. AIM OF THE STUDY: This study aimed to explore the role of detoxifying and blood-activating formulae in the treatment of unstable angina and the potential mechanism involved. MATERIALS AND METHODS: A total of 144 participants with unstable angina were randomly divided into experimental and control groups. Both groups were treated with standardized Western medicine; the experimental group was additionally treated with detoxifying and blood-activating Chinese medicine granules, which included 15 g of P. cuspidatum and 10 g of C. pinnatifida for 4 weeks. The primary endpoint was the frequency of weekly angina pectoris attacks before and after treatment. The secondary endpoints, also observed before and after treatment, included blood glucose, blood lipids, high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-6, IL-10, and adiponectin levels, as well as the ratio of pro/anti-inflammatory factors and evaluation scales of symptoms and syndromes in Chinese and Western medicine. RESULTS: In both experimental and control groups, the frequency of weekly angina pectoris attacks was lower after treatment (P < 0.01), but with no significant intergroup difference (P = 0.10). After intervention, the hs-CRP, TNF-alpha, and IL-6 levels decreased, while the IL-10 and adiponectin levels significantly increased in the experimental group (P < 0.05 or 0.01). The ratios of the inflammatory factors significantly decreased after treatment, particularly in the experimental group (P < 0.01). Symptoms and syndromes were also ameliorated in the experimental group (P < 0.01), showing a significant difference from the control group (P < 0.01). CONCLUSIONS: Detoxifying and blood-activating formulae can reduce the frequency and relieve symptoms of unstable angina, and this mechanism may be related to a regulation of the balance of pro- and anti-inflammatory factors. | Crataegus |
BACKGROUND: The association between advanced interatrial block (aIAB) and atrial fibrillation (AF) is known as Bayes' Syndrome." There is little information on the prognostic role that new speckle tracking echocardiographic (STE) imaging techniques could play in it. We have examined the relationship between left atrial (LA) STE and the prediction of new-onset AF and/or stroke in IAB patients. METHODS: This is an observational prospective and unicentric cohort study with 98 outpatients: 55 (56.2%) controls with normal ECG without IAB, 21 (21.4%) with partial IAB (pIAB) and 22 (22.4%) with aIAB. The end point was new-onset AF, ischemic stroke and the composite of both. RESULTS: During a mean follow-up of 1.9 (1.7-2.3) years, 20 patients presented the end point (18 new-onset AF and two strokes): 8 (14.5%) in the control group, 3 (14.3%) in pIAB and 9 (40.9%) in aIAB, p = 0.03. In multivariable comprehensive Cox regression analyses, a decrease in absolute value of strain rate during the booster pump function phase (SRa) was the only variable independently related to the appearance in the evolution of the end point, in the first model (age, P-wave duration and SRa): HR 19.9 (95% CI, 3.12-127.5), p = 0.002 and in the second (age, presence of aIAB and SRa): HR 24.2 (95% CI, 3.15-185.4), p = 0.002. CONCLUSIONS: In patients with IAB, a decrease in absolute value of LA SRa with STE predicts new-onset AF and ischemic stroke. Future studies should confirm our results and assess the prognostic usefulness of LA STE in patients with IAB." | Interatrial Block |
Dynamic light scattering (DLS) measurements were performed to study the binding of anionic surfactant alpha olefin sulfonate (AOS) to gelatin chains at various NaCl concentrations at 30 degrees C in aqueous sodium phosphate buffer (pH = 6.8) solutions. The surfactant concentration was varied from 0 to 80 mM and the NaCl concentrations chosen were 0.025, 0.05, and 0.1 M. AOS exhibited electrostatic binding to the positively charged sites of the polypeptide chain resulting in considerable reduction in its hydrodynamic radius up to critical micellar concentration (cmc = 8 mM for no salt, 0.01 and 0.025 M, and 5 mM for 0.05 M and 2 mM for 0.1 M solutions). The correlation function revealed the presence of two types of structures above cmc; namely the micelles of AOS and gelatin-AOS micelle complexes. The micellar radii (Rm), the effective gelatin-surfactant complex radii (Rc), have been determined as a function of salt concentration. No critical aggregation concentration (cac) was observed. The inter-gelatin-surfactant complex (kD1) and inter-micellar interactions (kD2), were determined by fitting the concentration dependence of Rm and Rc to a virial expansion in reduced concentration (c - cmc), which are compared. While kD1 showed strong ionic strength dependence, kD2 remained invariant of the same. The protein to surfactant binding ratio was found to be smaller than normal. Results have been discussed within the framework of the necklace-bead model of polymer-surfactant interactions. | Alkanesulfonates |
Although biomass fuel has always been regarded as a source of sustainable energy, it potentially emits polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs). This study investigated PCDD/F emissions from industrial boilers fired with three types of biomass fuel (i.e., bagasse, coffee residue, and biomass pellets) via stack sampling and laboratory analysis. The measured mass concentrations of PCDD/Fs varied among the boilers from 0.0491 to 12.7 ng Nm(-3) (11% O(2)), with the calculated average international toxic equivalent quantity (I-TEQ) from 0.00195 to 1.71 ng I-TEQ Nm(-3) (11% O(2)). Some of them were beyond the limit value for municipal waste incineration. 2,3,4,7,8-PeCDF could be used as a good indicator of dioxin-induced toxicity of stack flue gases from biomass-fired boilers. The PCDFs/PCDDs ratios were more than 1, likely indicating the formation of dioxins in the boilers favored by de novo synthesis. The emission factor (EF) of total PCDD/Fs averaged 5.35 ng I-TEQ kg(-1) air-dry biomass (equivalent to 39.0 ng kg(-1) air-dry biomass). Specifically, the mean EF was 6.94 ng I-TEQ kg(-1) (52.6 ng kg(-1)) for biomass-pellet-fired boiler, 11.8 ng I-TEQ kg(-1) (74.6 ng kg(-1)) for coffee-residue -fired boiler, and 0.0277 ng I-TEQ kg(-1) (0.489 ng kg(-1)) for bagasse-fired boilers. The annual PCDD/F emission was estimated to be 208 g I-TEQ in 2020 in China, accounting for approximately 2% of the total national annual emission of PCDD/Fs. The results can be used to develop PCDD/Fs emission inventories and offer valuable insights to authorities regarding utilizing biomass in industry in the future." | Dibenzofurans, Polychlorinated |
A novel consecutive three-component synthesis of 3-(hetero)aryl-1H-pyrazoles via room temperature Sonogashira arylation of propynal diethylacetal used as a propargyl aldehyde synthetic equivalent has been disclosed. The final acetal cleavage-cyclocondensation with hydrazine hydrochloride at 80 degrees C rapidly furnishes the title compounds in a one-pot fashion. | Pyrazoles |
BACKGROUND: Peritonitis in horses secondary to non-strangulating infarction (NSII) has a guarded prognosis, even after intestinal resection. In contrast, horses with idiopathic peritonitis respond well to medical treatment. Affected horses in both cases often show signs of both colic and systemic inflammation, but early diagnosis is crucial for optimal treatment and an accurate prognosis. One cause of NSII is thrombus formation secondary to Strongylus vulgaris larval migration. There has been a documented increase in S. vulgaris prevalence in Sweden since the implementation of selective anthelmintic treatment in 2007, which subsequently could result in a rise in NSII cases. In a retrospective clinical study, medical records from cases diagnosed with NSII of the pelvic flexure or idiopathic peritonitis from three equine referral hospitals in Sweden during 2017-2020 were reviewed. Information including demographic data, relevant medical history, and clinical- and laboratory parameters were obtained from patient records. To facilitate the differentiation between cases of idiopathic peritonitis and cases with confirmed NSII of the pelvic flexure, the aim of the study was to compare clinical and laboratory parameters, clinical progression and initial response to antimicrobial treatment. A secondary aim was to compare survival-rates. RESULTS: Horses with NSII (n = 20) were significantly more likely to present during the winter months with a poorer response to medical treatment within 48 h. Cases of idiopathic peritonitis (n = 107) had a 100% survival rate with medical treatment, although one case required surgical correction of a colon displacement. In comparison, all confirmed NSII cases were non-responsive to antimicrobial treatment, with a survival rate to discharge of 50% after colon resection. Specific rectal findings and peripheral blood neutropenia were strongly associated with NSII. CONCLUSIONS: In Sweden, idiopathic peritonitis cases still predominate over S. vulgaris associated NSII cases and have an excellent survival rate with antimicrobial treatment. However, horses presenting with septic peritonitis during the winter months with a palpable rectal mass and displaying fever and colic signs beyond 48 h of medical treatment are likely to suffer from NSII of the pelvic flexure and should be considered for abdominal surgery. | Strongylus |
An evaluation of Superose 6, a new high performance gel filtration medium, has been made for the rapid separation and quantitation of paraprotein polymers. There is a significant correlation between relative serum viscosity and the concentration of polymeric IgA as demonstrated by FPLC using the Superose 6 columns. The retention times of the columns are highly reproducible and allow good resolution of polymers and provide a simple way of separating IgG3 from albumin. Scaling up to the preparative Superose 6B could be achieved with little loss of resolution. | Paraproteins |
2-Deoxy-2-fluoro-D-[3H]glucose and 2-deoxy-2-fluoro-D-[3H]mannose have been prepared by tritiation of the corresponding unlabeled 2-fluoro sugars. The tritiated 2-fluoro sugars are phosphorylated and activated by UTP and by GTP to yield UDP-2-deoxy-2-fluoro-D-[3H]glucose, UDP-2-deoxy-2-fluoro-D-[3H]mannose, GDP-2-deoxy-2-fluoro-D-[3H]glucose and GDP-2-deoxy-2-fluoro-D-[3H]mannose in both cell types. The nucleotide derivatives could also be labeled in the nucleotide moiety by feeding the cells with [14C]uridine or [14C]guanosine in the presence of unlabeled 2-fluoro sugar. No evidence was obtained for metabolic steps in which the six-carbon chain of 2-fluoro sugars was not preserved. No epimerisation of the label to 2-deoxy-2-fluoro-D-[3H]galactose could be observed by radioactive gas-liquid chromatography of the enzymatic cleavage products of the different 2-fluoro sugar metabolites isolated from either cell type. Yeast and chick embryo cells both incorporate 2-deoxy-2-fluoro-D-[3H]glucose and 2-deoxy-2-fluoro-D-[3H]mannose specifically into glycoproteins, although this incorporation is very low when compared to the incorporation of 2-deoxy-D-[3H]glucose. | Deoxy Sugars |
Two major breakthroughs in the field of assisted reproduction-oocyte donation and oocyte vitrification-have joined forces to create the rapidly emerging phenomenon of commercial egg banks (CEBs). In this review, we examine the history of this concept, the operational models, the geographical variations, and the benefits and pitfalls of CEBs, including the ethical and legal dilemmas arising from gamete mobility. We highlight future directions in the brave new world of third-party reproduction. | Oocyte Donation |
BACKGROUND: Pseudoxanthoma elasticum (PXE) is a rare, autosomal recessive inheritable disorder characterized by progressive elastic fibre calcification. CASE DESCRIPTION: Here we describe two patients with different presentations of PXE. Patient A, an 11-year-old girl, visited the dermatologist because of yellow papules (pseudoxanthomas) on the side of her neck. With the aid of a skin biopsy, the dermatologist diagnosed PXE. Some years later, patient A developed symptoms of intermittent claudication due to arterial calcifications. Supervised exercise training diminished these symptoms. Patient B, a 55-year-old man, visited the ophthalmologist due to recent onset of metamorphopsia. The ophthalmologist discovered a subretinal haemorrhage and observed changes in the retina consistent with PXE. Severe loss of vision was prevented by intraocular anti-VEGF injections. Upon further investigation, pseudoxanthomas and arterial calcifications were found. CONCLUSION: PXE is a rare monogenetic disorder with dermatological, ocular and vascular manifestations. With these two case reports we have illustrated how the initial clinical presentation and symptomatology may vary widely. | Pseudoxanthoma Elasticum |
The soy phytoestrogen, genistein, induces thymic atrophy when administered to ovariectomized mice by injection or in the diet. Injected genistein also causes decreased humoral immunity, but the effects of genistein on cell-mediated immunity have not been addressed. Here we examined effects of injected and dietary genistein on cell-mediated immune responses. Female C57BL/6 mice (25- to 27-days-old) were ovariectomized, then placed on phytoestrogen-free feed 5 days later. Seven days after ovariectomy, they were given daily subcutaneous injections of either dimethylsulfoxide (DMSO) or genistein (8, 20, 80 mg/kg) for 28 days; some mice were given 80 mg/kg genistein plus the anti-estrogen ICI 182,780 (5 mg/kg/week). Cell-mediated immune response was tested by analyzing the delayed-type hypersensitivity (DTH) response to a hapten, 4-hydroxy-3-nitrophenyl acetyl succinimide (NP-O-SU), at the end of treatment. Reversibility of the effects of genistein was tested by measuring the DTH response in mice that were given genistein (20 or 80 mg/kg) for 28 days, then allowed to recover for 28 days. To determine if dietary genistein could affect cell-mediated immunity, mice ovariectomized as above were fed genistein at 0, 1000 or 1500 parts per million (ppm) for 28 days. There was a 46-67% decrease in the DTH response in the footpads of mice injected with 8-80 mg/kg genistein compared with controls (P<0.05 vs control for all treatment groups); these effects were reversible. On histopathological examination of the feet, there was decreased cell infiltration in genistein-treated animals compared with controls, and the numbers of CD4(+) and CD8(+) T cells in popliteal lymph nodes were reduced. The effects of genistein are mediated through both estrogen receptor (ER) and non-ER pathways, as the anti-estrogen ICI 182,780 only partially blocked the effects of genistein on the DTH response. Dietary genistein (1000 or 1500 ppm) decreased cell-mediated immunity while producing serum genistein concentrations in the physiological range for humans under certain nutritional conditions. Further work is needed to determine if dietary genistein and phytoestrogen exposure can produce effects on cell-mediated immunity in humans or other animals under various nutritional conditions. | Nitrohydroxyiodophenylacetate |
Two antiretroviral medicines recently came on the scene for people starting HIV treatment for the first time: Rilpivirine (brand name Edurant) won marketing approval in May, and the following August saw approval of Complera, a single-pill once-daily regimen that joins rilpivirine with two other drugs. This article explains the science behind rilpivirine and Complera and how these drugs measure up to the commonly prescribed efavirenz (Sustiva) and Atripla. lines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents, published by the U.S. Department of Health and Human Services (DHHS), currently lists efavirenz plus tenofovir/emtricitabine as the "preferred" NNRTI-based regimen for people starting antiretroviral therapy (ART) for the first time. In fact, the DHHS guidelines have listed efavirenz as a component of preferred starter regimens since 1998--a reflection of the drug's potency and long-lasting effects. Yet efavirenz has downsides, most famously its association with central nervous system side effects like dizziness" | Emtricitabine, Rilpivirine, Tenofovir Drug Combination |
We present a preliminary study of microwave head imaging using a three-dimensional (3-D) implementation of the distorted Born iterative method (DBIM). Our aim is to examine the benefits of using the more computationally intensive 3-D implementation in scenarios where limited prior information is available, or when the target occupies an area that is not covered by the imaging array's transverse planes. We show that, in some cases, the 3-D implementation outperforms its two-dimensional (2-D) counterpart despite the increased number of unknowns for the linear problem at each DBIM iteration. We also discuss how the 3-D algorithm can be implemented efficiently using graphic processing units (GPUs) and validate this implementation with experimental data from a simplified brain phantom. In this work, we have implemented a non-linear microwave imaging approach using DBIM with GPU-accelerated FDTD. Moreover, the paper offers a direct comparison of 2-D and 3-D microwave tomography implementations for head imaging and stroke detection in inhomogenous anatomically complex numerical head phantoms. | Microwave Imaging |
Sarcopenia is an age-related condition of slow, progressive loss of muscle mass and strength, which contributes to frailty, increased risk of hospitalization and mortality, and increased health care costs. The incidence of sarcopenia is predicted to increase to >200 million affected older adults worldwide over the next 40 years, highlighting the urgency for understanding biological mechanisms and developing effective interventions. An understanding of the mechanisms underlying sarcopenia remains incomplete. Iron in the muscle is important for various metabolic functions, including oxygen supply and electron transfer during energy production, yet these same chemical properties of iron may be deleterious to the muscle when either in excess or when biochemically unshackled (eg, in ferroptosis), it can promote oxidative stress and induce inflammation. This review outlines the mechanisms leading to iron overload in muscle with aging and evaluates the evidence for the iron overload hypothesis of sarcopenia. Based on current evidence, studies are needed to (a) determine the mechanisms leading to iron overload in skeletal muscle during aging; and (b) investigate whether skeletal muscles are functionally deficient in iron during aging leading to impairments in oxidative metabolism. | Iron Overload |
Proto-Kranz plants represent an initial phase in the evolution from C(3) to C(3)-C(4) intermediate to C(4) plants. The ecological and adaptive aspects of C(3)-C(4) plants would provide an important clue to understand the evolution of C(3)-C(4) plants. We investigated whether growth temperature and nitrogen (N) nutrition influence the expression of C(3)-C(4) traits in Chenopodium album (proto-Kranz) in comparison with Chenopodium quinoa (C(3)). Plants were grown during 5 weeks at 20 or 30 degrees C under standard or low N supply levels (referred to as 20SN, 20LN, 30SN, and 30LN). Net photosynthetic rate and leaf N content were higher in 20SN and 30SN plants than in 20LN and 30LN plants of C. album but did not differ among growth conditions in C. quinoa. The CO(2) compensation point (Gamma) of C. album was lowest in 30LN plants (36 micromol mol(-1)), highest in 20SN plants (51 micromol mol(-1)), and intermediate in 20LN and 30SN plants, whereas Gamma of C. quinoa did not differ among the growth conditions (51-52 micromol mol(-1)). The anatomical structure of leaves was not considerably affected by growth conditions in either species. However, ultrastructural observations in C. album showed that the number of mitochondria per mesophyll or bundle sheath (BS) cell was lower in 20LN and 30LN plants than in 20SN and 30SN plants. Immunohistochemical observations revealed that lower accumulation level of P-protein of glycine decarboxylase (GDC-P) in mesophyll mitochondria than in BS mitochondria is the major factor causing the decrease in Gamma values in C. album plants grown under low N supply and high temperature. These results suggest that high growth temperature and low N supply lead to the expression of C(3)-C(4) traits (the reduction of Gamma) in the proto-Kranz plants of C. album through the regulation of GDC-P expression." | Glycine Dehydrogenase (Decarboxylating) |
BACKGROUND: Autoimmune lymphoproliferative syndrome (ALPS) is a genetic disorder of lymphocyte homeostasis due to impaired apoptosis. It was initially regarded as a very rare disease, but recent studies show that it may be more common than previously thought. Defects in a couple of genes have been identified in a proportion of patients with ALPS, but around one-third of such patients remain undefined genetically. OBJECTIVE: We describe 2 siblings presenting with ALPS-like disease. This study aimed to identify the genetic cause responsible for this phenotype. METHODS: Whole-exome sequencing and molecular and functional analyses were used to identify and characterize the genetic defect. Clinical and immunological analysis was also performed and reported. RESULTS: The 2 patients presented with chronic lymphadenopathy, hepatosplenomegaly, autoimmune hemolytic anemia, immune thrombocytopenia, and the presence of antinuclear autoantibody and other autoantibodies, but normal double-negative T cells. They also suffered from recurrent infections. Novel compound heterozygous mutations of RASGRP1 encoding Ras guanyl nucleotide releasing protein 1 were identified in the 2 siblings. The mutations impaired T-cell receptor signaling, leading to defective T-cell activation and proliferation, as well as impaired activation-induced cell death of T cells. CONCLUSIONS: This study shows for the first time that RASGRP1 mutation should be considered in patients with ALPS-like disease. We also propose to investigate the intracellular proteins involved in the T-cell receptor signaling pathway in similar patients but with unknown genetic cause." | Autoimmune Lymphoproliferative Syndrome |
Tissue engineering as a rapidly developing branch of science offers hope for the use of its products in medical practice. Among the components of tissue substitutes are different types of cells, especially stem cells. A promising source of adult stem cells is hair follicles. Development of follicles in the skin takes place even during fetal life. They arise due to the impact of epidermal and mesenchymal cells. The next steps in the formation of hair follicles are under the control of many factors. Hair follicles are the niche of various stem cell populations and are a major source of cells responsible for regeneration of the hair, sebaceous glands and epidermis. The term hair follicle stem cells" is most often used in relation to the epithelial cell population. Hair follicle stem cell studies are complicated by the fact that these stem cells divide relatively rarely. The aim of this study is to present the characteristics of cells isolated from the hair follicle in the light of recent research." | Hair Follicle |
Peripheral human lymphocytes reacted with fluorescein diacetate and analyzed by flow cytometry produced a bimodal fluorescence distribution that was shown to be attributable to the differential staining of T and B lymphocytes. Lymphocytes were fractionated into rosetting (T cell) and nonrosetting (B cell) populations. Both subfractions were reacted with fluorescein diacetate and analyzed by flow cytometry. The rosetting fraction was more fluorescent than the nonrosetting fraction, and the analysis of an appropriate mixture of the subfractionated populations produced a fluorescence distribution very similar to that obtained with unfractionated lymphocytes. | Immune Adherence Reaction |
A reliable indicator is needed to predict and reduce the risk of infection associated with fecal contamination of surface water. Since Pepper mild mottle virus (PMMoV), human picobirnaviruses (hPBV) and Torque teno virus (TTV) have been detected at substantial levels in human feces, we explored whether detection of nucleic acids of these viruses is a suitable indicator of fecal contamination in river water. From September 2008 to December 2009, water samples (n = 111) were collected from the Ruhr and Rhine rivers and from the influents and effluents of a wastewater plant (n = 12). Quantitative real time (RT-) PCR was used to determine the abundance of PMMoV, hPBV, and TTV in comparison to human adenoviruses (HAdV) and human polyomaviruses (HPyV) that are frequently detected in surface water and were previously proposed as indicators. While PMMoV was detected in all river water samples, the other viruses were detected less frequently. The concentration of the studied viruses in positive river water ranged from 5 x 10(1) to 1.07 x 10(6) genome equivalents per liter (gen.equ./l). All wastewater samples were positive for PMMoV, HAdV and HPyV, while TTV and hPBV were detected in 6/12 and 3/12 of samples, respectively. To determine if PMMoV is specific to human-derived fecal waste, fecal samples from human (n = 20) and animal (n = 53) were also tested. In contrast to the ubiquity of PMMoV in human feces (19/20) the virus was only detected at low concentration in a minority of the animal fecal samples tested (7/15 from chicken, 1/10 from Geese and 1/6 from cows). Therefore, in this setting TTV and hPBV do not seem to be suitable indicators of fecal contamination in water. Whereas, the high excretion level and dissemination of PMMoV in human sewage and river water suggest that PMMoV could be a promising indicator of fecal pollution in surface water. | Picobirnavirus |
Water-soluble chlorophyll-binding proteins (WSCPs) from Brassicaceae constitute a small family of non-photosynthetic proteins that may provide a useful benchmark and model system for studying molecular aspects of chlorophyll-protein interactions such as the tuning of absorption and emission spectra, and binding selectivity. WSCP apo-proteins are readily expressed by recombinant DNA techniques and can be assembled in vitro with natural and synthetic chlorophyll derivatives. The complexes with native chlorophylls are exceptionally stable toward thermal dissociation and protein denaturation due to hydrophobic interactions with the chlorophyll's phytyl chains that stabilize the core of the WSCP tetrameric complexes. However, assembly requires the use of detergents or water-in-oil emulsions to introduce the hydrophobic pigments into the water-soluble apo-proteins. Here, we explore the direct assembly of recombinant WSCPs with the water-soluble phytyl-free chlorophyll analogue chlorophyllide a in aqueous solutions. We show that the complexes formed by mixing chlorophyllide and WSCP apo-proteins are exclusively tetrameric, and while they lack the extreme thermostability of the respective chlorophyll complexes, they are still thermostable up to around 60 degrees C. Their absorption and CD spectra are very similar to the chlorophyll complexes albeit slight peak shifts and broadening of the bands indicate variations in pigment and protein conformations, and less rigid structures. Simplifying the assembly process of WSCPs opens new possibilities for their use in modelling natural chlorophyll-protein complexes, and as templates for designing novel artificial protein-pigment complexes. | Chlorophyll Binding Proteins |
BACKGROUND AND AIM: One source of error with near-infrared spectroscopy (NIRS) is the assumption that the measured tissue is optically homogeneous. This is not always the case. Our aim is to assess the impact of tissue homogeneity (TH) on the precision of NIRS measurements in neonates. METHODS: On 36 term and 27 preterm neonates at least five 1-min measurements are performed on each subject using the OxiplexTS. The sensor position is slightly changed before each measurement while assessing TH. The precision for cerebral tissue oxygenation saturation (StO(2)) and total hemoglobin concentration (tHb) are calculated by repeated measures analysis of variance. RESULTS: The mean StO(2) is not significantly different between term and preterm infants. The mean tHb is significantly lower in preterm infants (p < 0.01). With increasing TH, the precision of StO(2) increase from 5.6 to 4.6% for preterm and from 11.0 to 2.0% for term infants; the precision of tHb increases from 10.1 to 7.5muM for preterm and from 16.4 to 3.5 muM for term infants. The precision for StO(2) is higher in term than in preterm infants. The precision for tHb shows no significant difference between the two groups. CONCLUSIONS: The precision of NIRS measurements correlates with tissue homogeneity. | Hemoglobinometry |
Land use change has the potential to cause severe ecosystem degradation and drive changes in disease transmission and emergence. Broadscale clearing of native vegetation for agriculture in southwestern Australia has resulted in severe ecosystem degradation, which has been compounded by the subsequent development of large areas of dryland salinity. The mosquito-borne disease, Ross River virus (RRV), has been noted as a potential adverse human health outcome in these salinity affected regions. The association between dryland salinity and RRV disease was therefore tested by undertaking a spatial analysis of disease notification records using standard and Bayesian techniques. To overcome inherent limitations with notification data, serological RRV antibody prevalence was also investigated. Neither method revealed a significant association with dryland salinity, however, the spatial scale imposed limited the sensitivity of both studies. Thus, further multidisciplinary studies are required to overcome these limitations and advance understanding of this ecosystem health issue, particularly using variables that can be investigated on a finer scale. | Ross River virus |
The fruits of Arctium lappa L. is an often-used herbal drug in traditional Chinese medicine for the treatment of common cold caused by wind and heat. This drug contained many constituents, principally arctiin, with arctigenin in smaller amount. In this work, arctiin has been isolated from the fruits of Arctium lappa, and then enzymolyzed into arctigenin. The obtained arctiin and arctigenin were characterized and then used as standards for their determination in the crude drug by HPLC. The method is simple, rapid and accurate. | Benzyl Compounds |
PURPOSE: The study aims at validating a new pictorial tool, the Silhouette Rating Scale (SRS). It consists of a series of nine female or male silhouettes. It was created to assess current and ideal body size evaluation, and body dissatisfaction. Our aims were to test the concurrent, convergent and discriminant validity of the scale, evaluating possible gender differences. METHOD: A first sample of 754 young adults (age M = 26.10 +/- 8.50, males N = 218) and a second sample of 210 young adults (age M = 21.19 +/- 3.22, males = 43) completed the SRS, and other self-report measures assessing body size evaluation, disordered eating, body satisfaction, depression, emotion regulation and insomnia. RESULTS: Statistical analyses performed on the first sample largely support the concurrent validity of the scale. Results obtained from the second sample confirm its convergent validity, showing strong correlations with the Contour Drawing Rating Scale. In addition, the correlations performed between the three responses of the SRS and other measures of eating disorders, depression, insomnia and emotion regulation indicated a good discriminant validity, though some of the variables measured seem to be significantly correlated. CONCLUSIONS: The SRS is a reliable and valid tool for assessing current body size, body ideal and body dissatisfaction as compared to other widely used scales. It guarantees the universality of use thanks to the absence of details related to ethnicity or culture and at the same time, maintaining a right level of realism. Future studies will evaluate test-retest validity and its potential within clinical populations. LEVE OF EVIDENCE: V, descriptive cross sectional study. | Body Dissatisfaction |
OBJECTIVE: To reveal the clinical, morphological and pathogenic features of gastroduodenal erosions and ulcers in unstable angina. METHODS: 135 patients with unstable angina were examined and divided into 2 groups, depending on the presence of a pathological process in the gastroduodenal zone. The state of microcirculation in the tissues of the gastroduodenal zone, secretory and motor function of the stomach were estimated by complex of techniques, adapted to the severity of the patients. RESULTS: It is found that the pathological process in the gastroduodenal zone in patients with unstable angina was presented primarily by acute erosions, less - acute ulcers or recurrent peptic ulcer disease. In this case, the leading symptom of acute erosions was dyspepsia, that as a rule prevailed over the indistinct abdominal pain, and often disappeared in the first few days of treatment. Clinical picture of acute ulcers was determined by gastric dyspepsia and was often combined with abdominal pain and symptoms of gastrointestinal bleeding. The recurrence of peptic ulcer disease was characterized by the combination of moderate abdominal pain, often with migration in retrosternal and cardiac area and loss of circadian rhythm inherent in anthro-duodenal ulcer localization, and dyspeptic disorders. The severity of symptoms of ulcerous process was gradually decreased with time, but in most patients, they had remained by the end of the 2nd week of treatment. The basis of development of erosions and ulcers in unstable angina were the focal mainly thrombohaemorrhagic disorders of the terminal blood flow in the gastroduodenal mucosa. Its were combined with changes in the functional state of the stomach, manifested with an increase activity of acid-peptic factor, reduced production of gastromucoproteins, hypomotor dyskinesia and discoordination of anthro-duodenal propulsion on the hypotonic type. CONCLUSION: Erosive and ulcerative lesions of gastroduodenal zone in unstable angina have a number of clinical and pathogenetic features that should be considered in the process of diagnosis and treatment. | Angina, Unstable |
BACKGROUND: Functional constipation is a disease with a high incidence, which has a bad effect on general health, mental health, and social functioning. However, current treatment is sometimes unsatisfactory. Acupuncture has been proven effective in some randomized controlled trials. Acupressure is a subtype of acupuncture and can be manipulated by the patients at home. But the evidence is limited now. This study aims to provide some strict evidence for the use of self-administered acupressure in the treatment of functional constipation. METHODS: This 2-armed, parallel, nonspecific controlled, randomized trial will be conducted at The Third Affiliated Hospital of Zhejiang Chinese Medical University in Hangzhou. A total of 154 FC patients will be enrolled into the acupoint group and the sham acupoint group with a ratio of 1:1 into this trial and it will consist of a 2-week run-in period, an 8-week intervention period, and an 8-week follow-up period. The treatment will be done by the patients themselves at home twice a day and they should sign in on the WeChat APP every day to make sure they have done the acupressure. The outcome will also be collected in WeChat APP through the diary and questionnaires. For the one who is unable to use the WeChat, the print edition of the diary and questionnaires are provided and the supervision will be done by the short message. The primary outcome will be the proportion of participants whose CSBM>/=3 during week 3 to 10. The secondary outcome will be the proportion of participants whose CSBM >/=3 between 2 groups in week 11 to 18, Spontaneous bowel movements, Bristol Stool Form Scale, Straining severity scores, Patient assessment of constipation quality of life, and Medicine use. DISCUSSION: Acupressure is not an invasive method and can be done by the patient itself at home. We hope this trial will provide credible evidence to the application of self-acupressure for the management of severe chronic functional constipation. TRIAL REGISTRATION: This trial has been registered at the Chinese Clinical Trial Registry (ChiCTR2000038594). | Acupressure |
CONTEXT: Despite the effectiveness of balance training, the exact parameters needed to maximize the benefits of such programs remain unknown. One such factor is how individuals should progress to higher levels of task difficulty within a balance-training program. Yet no investigators have directly compared different balance-training-progression styles. OBJECTIVE: To compare an error-based progression (ie, advance when proficient at a task) with a repetition-based progression (ie, advance after a set amount of repetitions) style during a balance-training program in healthy individuals. DESIGN: Randomized controlled trial. SETTING: Research laboratory. PATIENTS OR OTHER PARTICIPANTS: A total of 28 (16 women, 12 men) physically healthy young adults (age = 21.57 +/- 3.95 years, height = 171.60 +/- 11.03 cm, weight = 72.96 +/- 16.18 kg, body mass index = 24.53 +/- 3.7). INTERVENTION(S): All participants completed 12 supervised balance-training sessions over 4 weeks. Each session consisted of a combination of dynamic unstable-surface tasks that incorporated a BOSU ball and lasted about 30 minutes. MAIN OUTCOME MEASURE(S): Static balance from an instrumented force plate, dynamic balance as measured via the Star Excursion Balance Test, and ankle force production in all 4 cardinal planes of motion as measured with a handheld dynamometer before and after the intervention. RESULTS: Selected static postural-control outcomes, dynamic postural control, and ankle force production in all planes of motion improved (P < .05). However, no differences between the progression styles were observed (P > .05) for any of the outcome measures. CONCLUSIONS: A 4-week balance-training program consisting of dynamic unstable-surface exercises on a BOSU ball improved dynamic postural control and ankle force production in healthy young adults. These results suggest that an error-based balance-training program is comparable with but not superior to a repetition-based balance-training program in improving postural control and ankle force production in healthy young adults. | Postural Balance |
Due to its importance both in the clearance of pathogens that contribute as rheumatic etiological agents and in the disposal of apoptotic bodies and potential autoimmune initiators, deficiencies of the components of the lectin pathway of complement have been found to increase susceptibility and modulate the severity of most rheumatic disorders. This chapter introduces the general aspects of the structure, function, and genetics of lectin pathway components and summarizes current knowledge of the field regarding rheumatic diseases predisposition and modulation." | Complement Pathway, Mannose-Binding Lectin |
Rimonabant is the first selective blocker of the cannabinoid-1 receptor in development for the treatment of obesity, diabetes mellitus, and cardiometabolic risk factors. (Recently, an FDA Advisory Committee recommended a delay in the approval of rimonabant because of safety issues that need to be addressed in further studies.) Although it is associated with favorable effects on weight, waist circumference, serum lipids, C-reactive protein, and an improvement in glycemic control in type 2 diabetes, there are concerns about side effects. Generally, rimonabant has been well tolerated, with a primary side effect of nausea. Other side effects seen in trials have been anxiety and depressive symptoms, as well as neurologic events, albeit at low rates. When rimonabant becomes clinically available, physicians should be vigilant regarding the expected side effects and use alternative therapies if needed. | Rimonabant |
Named after Hans Christian Gram who developed the method in 1884, the Gram stain allows one to distinguish between Gram-positive and Gram-negative bacteria on the basis of differential staining with a crystal violet-iodine complex and a safranin counterstain. The cell walls of Gram-positive organisms retain this complex after treatment with alcohol and appear purple, whereas gram-negative organisms decolorize following such treatment and appear pink. The method described here is useful for assessing bacterial contamination of tissue culture samples or for examining the Gram stain status and morphological features of bacteria isolated from mixed or isolated bacterial cultures. | Gentian Violet |
PURPOSE OF REVIEW: Intense interventions are ongoing to combat malaria. Malaria mortality investigation remains as an intense area of study with controversies, competing models of pathogenesis, and a few carefully proceeding clinical trials. This review suggests a reframing of the question of cerebral malaria pathology in light of recent findings to focus on dissection of pathogenesis that will lead to effective treatments. RECENT FINDINGS: Pediatric and adult manifestations of cerebral malaria within the retina allows for intense study of the clinical defined patients including the advent of multiple imaging modalities in endemic regions. Basic pathogenesis in mouse models and human studies, focused on cytokines, inflammation, cytoadherence, and endothelial activation, continues to be elucidated molecule by molecule. Coagulation is variably important and may serve as one of several unifying principles of current pathogenesis models. Parasite-derived molecules - surface or soluble - remain necessary but not sufficient to explain pathologic manifestations. SUMMARY: As we close the gaps in the fight against global malaria, the question of cerebral malaria mortality remains a source of great concern. We currently have no effective means of reversal of coma or impacting mortality in the comatose patient. As transmission is broken, cerebral malaria will spread to older age groups in Africa where we expect mortality will be higher. Continued directed study of pathogenesis with the primary goal of efficacious interventions in the comatose is a necessity. | Malaria, Cerebral |
PURPOSE: Head trauma is common in the emergency department. Identifying the few patients with serious injuries is time consuming and leads to many computerized tomographies (CTs). Reducing the number of CTs would reduce cost and radiation. The aim of this study was to evaluate the characteristics of adults with head trauma over a 1-year period to identify clinical features predicting intracranial hemorrhage. METHODS: Medical record data have been collected retrospectively in adult patients with traumatic brain injury. A total of 1638 patients over a period of 384 days were reviewed, and 33 parameters were extracted. Patients with high-energy multitrauma managed with ATLS were excluded. The analysis was done with emphasis on patient history, clinical findings, and epidemiological traits. Logistic regression and descriptive statistics were applied. RESULTS: Median age was 58 years (18-101, IQR 35-77). High age, minor head injury, new neurological deficits, and low trauma energy level correlated with intracranial hemorrhage. Patients younger than 59 years, without anticoagulation or antiplatelet therapy who suffered low-energy trauma, had no intracranial hemorrhages. The hemorrhage frequency in the entire cohort was 4.3% (70/1638). In subgroup taking anticoagulants, the frequency of intracranial hemorrhage was 8.6% (10/116), and in the platelet-inhibitor subgroup, it was 11.8% (20/169). CONCLUSION: This study demonstrates that patients younger than 59 years with low-energy head trauma, who were not on anticoagulants or platelet inhibitors could possibly be discharged based on patient history. Maybe, there is no need for as extensive medical examination as currently recommended. These findings merit further studies." | Intracranial Hemorrhage, Traumatic |
Low-lipid content algae have demonstrated potential in the bio-crude production because of their high yield and robust ability to adapt to hostile cultivation environment in mass cultivation. Hydrothermal liquefaction (HTL) technology is an effective method to convert wet algae to bio-crudes directly. In this study, the HTL processes of two low-lipid content algae, Nannochloropsis sp. and Sargassum sp., were investigated under various reaction temperatures (260-320 degrees C). Results showed that the bio-crudes yield of Nannochloropsis sp. (39.05 wt% to 54.11 wt%) was significantly higher than that of Sargassum sp. (3.11 wt% to 9.49 wt%). The higher heating value of Nannochloropsis sp. (35.92 MJ/kg to 37.88 MJ/kg) were also slightly higher than that of Sargassum sp., (33.63 MJ/kg to 35.23 MJ/kg). GC-MS analyses showed that Nannochloropsis sp. bio-crude mainly contained amides and N-heterocyclic compounds while Sargassum sp. bio-crude mainly contained N-heterocyclic compounds and ketones. Alcohols were the major aqueous phase compounds for both algae. For Nannochloropsis sp., glycerin accounted for the largest proportion in alcohols, while dianhydromannitol and 1,5-anhydro-d-mannitol were the major alcohols component for Sargassum sp. Based on the compositions of the HTL products and the feedstock, a reaction pathway network of the HTL process of low-lipid algae was proposed in this study. Amino acids related interactions like acylation and Maillard reaction were prominent in HTL process of these two algae, which effectively converted protein and carbohydrate compounds into bio-crudes. | Sargassum |
Acidiphilium cryptum JF-5, an acidophilic iron-respiring Alphaproteobacterium, has the ability to reduce chromate under aerobic and anaerobic conditions, making it an intriguing and useful model organism for the study of extremophilic bacteria in bioremediation applications. Genome sequence annotation suggested two potential mechanisms of Cr(VI) reduction, namely, a number of c-type cytochromes, and a predicted NADPH-dependent Cr(VI) reductase. In laboratory studies using pure cultures of JF-5, an NADPH-dependent chromate reductase activity was detected primarily in soluble protein fractions, and a periplasmic c-type cytochrome (ApcA) was also present, representing two potential means of Cr(VI) reduction. Upon further examination, it was determined that the NADPH-dependent activity was not specific for Cr(VI), and the predicted proteins were not detected in Cr(VI)-grown cultures. Proteomic data did show measureable amounts of ApcA in cells grown with Cr(VI). Purified ApcA is reducible by menadiol, and in turn can reduce Cr(VI), suggesting a means to obtain electrons from the respiratory chain and divert them to Cr(VI). Electrochemical measurements confirm that Cr reduction by ApcA is pH dependent, with low pH being favored. Homology modeling of ApcA and comparison to a known Cr(VI)-reducing c-type cytochrome structure revealed basic amino acids which could interact with chromate ion. From these studies, it can be concluded that A. cryptum has the physiologic and genomic capability to reduce Cr(VI) to the less toxic Cr(III). However, the expected chromate reductase mechanism may not be the primary means of Cr(VI) reduction in this organism. | Acidiphilium |
Real-time imaging was used to study the effects of a novel Fusarium-specific cyanoacrylate fungicide (JS399-19) on growth and morphology of four Fusarium sp. This fungicide targets the motor domain of type I myosin. Fusarium graminearum PH-1, Fusarium solani f. sp. pisi 77-13-4, Fusarium avenaceum IBT8464, and Fusarium avenaceum 05001, which has a K216Q amino-acid substitution at the resistance-implicated site in its myosin type I motor domain, were analyzed. Real-time imaging shows that JS399-19 inhibits fungal growth but not to the extent previously reported. The fungicide causes the hypha to become entangled and unable to extend vertically. This implies that type I myosin in Fusarium is essential for hyphal and mycelia propagation. The K216Q substitution correlates with reduced susceptibility in F. avenaceum. | Myosin Type I |
Structures of the cytochrome b(6)f complex obtained from the thermophilic cyanobacterium Mastigocladus laminosus and the green alga Chlamydomonas reinhardtii, whose appearance in evolution is separated by 10(9) years, are almost identical. Two monomers with a molecular weight of 110,000, containing eight subunits and seven natural prosthetic groups, are separated by a large lipid-containing quinone exchange cavity". A unique heme, heme x, that is five-coordinated and high-spin, with no strong field ligand, occupies a position close to intramembrane heme b(n). This position is filled by the n-side bound quinone, Q(n), in the cytochrome bc(1) complex of the mitochondrial respiratory chain. The structure and position of heme x suggest that it could function in ferredoxin-dependent cyclic electron transport as well as being an intermediate in a quinone cycle mechanism for electron and proton transfer. The significant differences between the cyanobacterial and algal structures are as follows. (i) On the n-side, a plastoquinone molecule is present in the quinone exchange cavity in the cyanobacterial complex, and a sulfolipid is bound in the algal complex at a position corresponding to a synthetic DOPC lipid molecule in the cyanobacterial complex. (ii) On the p-side, in both complexes a quinone analogue inhibitor, TDS, passes through a portal that separates the large cavity from a niche containing the Fe(2)S(2) cluster. However, in the cyanobacterial complex, TDS is in an orientation that is the opposite of its position in the algal structure and bc(1) complexes, so its headgroup in the M. laminosus structure is 20 A from the Fe(2)S(2) cluster." | Cytochrome b6f Complex |
We describe a 70-year-old Haitian man who had been taking warfarin for 5 years for atrial fibrillation and pulmonary hypertension. This patient had his international normalized ratio (INR) checked in the pharmacist-run anticoagulation clinic and was followed monthly. Prior to the interaction, his INR was therapeutic for 5 months while taking warfarin 10.5 mg/d. The patient presented with an INR > 8.0. Patient held 4 days of warfarin and restarted on warfarin 8.5 mg/d. Two weeks later, his INR was 2.5. After continuing dose, patient presented 2 weeks later and INR was 4.8. Upon further questioning, the patient stated he recently began ingesting mauby. Mauby is a bitter dark liquid extracted from the bark of the mauby tree that is commonly used in the Caribbean population as a folk remedy with many health benefits. This case report illustrates that mauby may have a probable drug-herb interaction (Naranjo Algorithm Score of 6) when given with warfarin. There is a lack of published literature and unclear information on the Internet describing the interaction of mauby and warfarin. Health professionals should be cautious regarding interactions between warfarin and mauby until the interaction is fully elucidated. | Colubrina |
In this 1-year study, 35 (1.2%) of 2,912 nasopharyngeal aspirates were positive for human parainfluenza virus 4 (HPIV4) by reverse transcription-PCR. Patients with HPIV4 infection were mainly young children and immunocompromised adults. In contrast to the reported predominance of HPIV4A infection, molecular subtyping revealed that 15 (44%) cases were caused by HPIV4B. | Parainfluenza Virus 4, Human |
Prion protein is a glycosyl-phosphatidyl-inositol anchored glycoprotein localized on the surface and within a variety of cells. Its conformation change is thought to be essential for the proliferation of prion neurodegenerative diseases. Using the yeast two-hybrid assay we identified an interaction between prion protein and clusterin, a chaperone glycoprotein. This interaction was confirmed in a mammalian system by in vivo co-immunoprecipitation and in vitro by circular dichroism analysis. Through deletion mapping analysis we demonstrated that the alpha subunit, but not the beta subunit, of clusterin binds to prion and that the C-terminal 62 amino acid segment of the putative alpha helix region of clusterin is essential for the binding interaction. The full prion protein as well as the N-terminal section (aa 23-95) and C-terminal (aa 96-231) were shown to interact with clusterin. These findings provide new insights into the molecular mechanisms of interaction between prion and clusterin protein and contribute to the understanding of prion protein's physiological function. | PrPC Proteins |
AIMS: The mechanism responsible for premature ventricular complex (PVC)-mediated left ventricular (LV) dysfunction remains unclear. We sought to determine the electrocardiographic and electrophysiological characteristics of PVC-mediated LV dysfunction. METHODS AND RESULTS: One hundred and twenty-seven patients who underwent radiofrequency catheter ablation (RFCA) for frequent PVCs (PVCs burden >/=10%/24 h) and had no significant structural heart disease were investigated. Left ventricular dysfunction (ejection fraction < 50%) was present in 28 of 127 patients (22.0%). The mean PVC burden (31 +/- 11 vs. 22 +/- 10%, P < 0.001), the presence of non-sustained ventricular tachycardia (53.6 vs. 33.3%, P = 0.05), and the presence of a retrograde P-wave following a PVC (64.3 vs. 30.3%, P = 0.001) were significantly greater in those with LV dysfunction than in those with normal LV function. The cut-off PVC burden related to LV dysfunction was 26%/day, with a sensitivity of 70% and a specificity of 78%. The PVC morphology, QRS axis, QRS width, coupling interval, the presence of interpolation, and PVC emergence pattern during exercise electrocardiogram were not significantly different between the two groups. The origin sites of PVCs, the acute success rate, and the recurrence rate during follow-up after RFCA were similar. In a multivariate analysis, the PVC burden (odds ratio 2.94, 95% confidence interval 0.90-3.19, P = 0.006) and the presence of retrograde P-waves (odds ratio 2.79, 95% confidence interval 1.08-7.19, P = 0.034) were independently associated with PVC-mediated LV dysfunction. CONCLUSION: A higher PVC burden (>26%/day) and the presence of retrograde P-waves were independently associated with PVC-mediated LV dysfunction." | Ventricular Premature Complexes |
Two ribosome-inactivating proteins, trichosanthin and alpha-momorcharin, have been studied in the forms of complexes with ATP or formycin, by an X-ray-crystallographic method at 1.6-2.0 A (0.16-0.20 nm) resolution. The native alpha-momorcharin had been studied at 2.2 A resolution. Structures of trichosanthin were determined by a multiple isomorphous replacement method. Structures of alpha-momorcharin were determined by a molecular replacement method using refined trichosanthin as the searching model. Small ligands in all these complexes have been recognized and built on the difference in electron density. All these structures have been refined to achieve good results, both in terms of crystallography and of ideal geometry. These two proteins show considerable similarity in their three-dimensional folding and to that of related proteins. On the basis of these structures, detailed geometries of the active centres of these two proteins are described and are compared with those of related proteins. In all complexes the interactions between ligand atoms and protein atoms, including hydrophobic forces, aromatic stacking interactions and hydrogen bonds, are found to be specific towards the adenine base. The relationship between the sequence conservation of ribosome-inactivating proteins and their active-centre geometry was analysed. A depurinating mechanism of ribosome-inactivating proteins is proposed on the basis of these results. The N-7 atom of the substrate base group is proposed to be protonated by an acidic residue in the active centre. | Trichosanthin |
Leishmania species show a significant variation in their sensitivity to established and experimental drugs. Molecular techniques to identify species in clinical infections rapidly could be used to guide treatment. Molecular markers are required to detect and monitor acquired resistance to antimonial drugs. Reporter genes and the polymerase chain reaction will improve assays both in vitro and in vivo for the identification and evaluation of new drugs. | Parasitic Sensitivity Tests |
With the increasing interest in big data and health services research, use of administrative databases is becoming commonplace in health care studies, including in neurosurgery. Administrative data offer the unique advantage of accessing large amounts of information previously collected from a population-based sample with geographic diversity. When using administrative data sets, researchers can benefit from application of risk adjustment instruments, which help stratify patients and tailor the original sample for specific research questions. The Charlson Comorbidity Index and Elixhauser Comorbidity Index are 2 of the most common indices. The Pediatric Medical Complexity Algorithm and Clinical Classification Software are other promising tools. Understanding of these tools may assist neurosurgeons who wish to critically assess research findings relevant to their clinical practice. In this review, an overview is presented of risk adjustment tools commonly used in adult as well as pediatric populations and their history, uses, limitations, and applications in neurosurgical research are summarized. | Risk Adjustment |
A new series of triazolotriazines variously substituted at the C5 and N7 (5-25) positions was synthesized and fully characterized at the four adenosine receptor (AR) subtypes. In particular, arylacetyl or arylcarbamoyl moieties were introduced at the N7 position, which enhanced affinity at the hA(2B) and hA(3) ARs, respectively, when utilized on the pyrazolo-triazolopyrimidine nucleus as we reported in the past. In general, compounds with a free amino group at the 7 position (5, 6), showed good affinity at the rat (r) A(2A) AR (range 18.3-96.5nM), while the introduction of a phenylcarbamoyl moiety at the N7 position (12, 19, 24) slightly increased the affinity at the hA(3) AR (range 311-633nM) with respect to the unsubstituted derivatives. The binding profiles of the synthesized analogues seemed to correlate with the substitutions at the C5 and N7 positions. At the hA(2B) AR, derivative 5, which contained a free amino group at the 7 position, was the most potent (EC(50) 3.42microM) and could represent a starting point for searching new non-xanthine hA(2B) AR antagonists. Molecular models of the rA(2A) and hA(3) ARs were constructed by homology to the recently reported crystallographic structure of the hA(2A) AR. A preliminary receptor-driven structure-activity relationship (SAR) based on the analysis of antagonist docking has been provided." | Adenosine A3 Receptor Antagonists |
The human Ureaplasma species are the most frequently isolated microorganisms from the amniotic fluid and placentae of women who deliver preterm and are also associated with spontaneous abortions or miscarriages, neonatal respiratory diseases, and chorioamnionitis. Despite the fact that these microorganisms have been habitually found within placentae of pregnancies with chorioamnionitis, the role of Ureaplasma species as a causative agent has not been satisfactorily explained. There is also controversy surrounding their role in disease, particularly as not all women infected with Ureaplasma spp. develop chorioamnionitis. In this review, we provide evidence that Ureaplasma spp. are associated with diseases of pregnancy and discuss recent findings which demonstrate that Ureaplasma spp. are associated with chorioamnionitis, regardless of gestational age at the time of delivery. Here, we also discuss the proposed major virulence factors of Ureaplasma spp., with a focus on the multiple-banded antigen (MBA), which may facilitate modulation/alteration of the host immune response and potentially explain why only subpopulations of infected women experience adverse pregnancy outcomes. The information presented within this review confirms that Ureaplasma spp. are not simply innocent bystanders" in disease and highlights that these microorganisms are an often underestimated pathogen of pregnancy." | Chorioamnionitis |
The surgical correction of refractive errors has gained widespread acceptance in the past 20 years, mainly through the introduction of the excimer laser. The excimer is used to ablate the cornea, renoving stromal tissue in the center (to correct myopia through flattening of the surface), or in the midperiphery (to steepen the cornea to correct hyperopia). Although excimer procedures dominate the field of refractive surgery, other approaches are also available. In the cornea itself, ring segments can be implanted, heat-induced coagulation effects can produce steepening, and cross-linking of the collagen fibers can stiffen a weakened structure. While all corneal procedures are extraocular, refractive surgery can also be performed within the eye. Special intraocular lenses can be implanted in the anterior chamber angle, fixated onto the iris, or placed in the posterior chamber in front of the crystalline lens. These so-called phakic intraocular lenses are available in different optical magnitudes and act to correct the patient's refractive error. Prebyopic individuals can have the crystalline lens removed in a procedure identical to cataract surgery. In such cases the lens is extracted even though no cataract is present, and an intraocular lens is implanted in the now empty capsular bag of the crystalline lens. The implanted lens serves to correct the preoperative refractive error." | Ophthalmologic Surgical Procedures |
The serological response of pigs to Erysipelothrix rhusiopathiae inoculation was monitored by a gel diffusion precipitin test (GDPT) using a crude, serotype-specific, autoclaved antigen and an enzyme-linked immunosorbent assay (ELISA) using a heat-extracted, alcohol precipitated and molecular seived antigen previously shown to react with serum from pigs infected with serotypes 1 or 2. All pigs receiving 3 or 5 weekly intravenous inoculations of either a highly virulent (VRS 229) or a lowly virulent isolate (VRS 252) produced GDPT-reactive antibody within 3 weeks, but only 44% were still reactive at 8 to 9.5 weeks. The ELISA response was significantly higher in pigs inoculated with the highly virulent strain, and was similar in pigs receiving 3 or 5 doses of either strain. In a dose-response trial, after 3 doses of VRS 229, GDPT reactivity occurred earlier and was stronger in pigs given higher doses of E. rhusiopathiae, but the response peaked 3 to 5 weeks after the start of challenge and was short lived. GDPT reactivity correlated with dose, but not with the severity of arthritis. The ELISA demonstrated specific IgG antibody was present by 2 weeks, and persisted to at least 11 weeks. The ELISA reactivity was significantly higher in pigs with arthritis than in pigs that received low doses and were not arthritic. Within groups of pigs with arthritis a significant, dose dependent, linear ELISA response developed but did not correlate with the presence or degree of arthritis at slaughter. Non-arthritic pigs had similar low ELISA responses to uninoculated controls. | Swine Erysipelas |
The C-terminal domain (CTD) of the largest subunit of RNA polymerase II (Pol II) is composed of tandem repeats of the heptapeptide Tyr1-Ser2-Pro3-Thr4-Ser5-Pro6-Ser7. The CTD of Pol II undergoes reversible phosphorylation during the transcription cycle, mainly at Ser2, Ser5, and Ser7. Dynamic changes in the phosphorylation patterns of the CTD are responsible for stage-specific recruitment of various factors involved in RNA processing, histone modification, and transcription elongation/termination. Human RNA polymerase II-associated protein 2 (RPAP2) was originally identified as a Pol II-associated protein and was subsequently shown to function as a novel Ser5-specific CTD phosphatase. Although a recent study suggested that RPAP2 is required for the efficient expression of small nuclear RNA genes, the role of RPAP2 in controlling the expression of protein-coding genes is unknown. Here, we demonstrate that the C-terminal region of RPAP2 interacts directly with the Pol II subunit Rpb6. Chromatin immunoprecipitation analyses of the MYC and GAPDH protein-coding genes revealed that RPAP2 occupied the coding and 3' regions. Notably, siRNA-mediated knockdown of RPAP2 caused defects in 3'-end formation of the MYC and GAPDH pre-mRNAs. These results suggest that RPAP2 controls Pol II activity through a direct interaction with Rpb6 and participates in pre-mRNA 3'-end formation. | RNA 3' End Processing |
BACKGROUND: Exosomes are nano-sized extracellular vesicles which are secreted by cells and usually found in body fluids. Previous research has shown that exosomal secretion and autophagy-lysosomal pathway synergistically participates in intracellular abnormal protein elimination. The main pathological manifestations of Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is abnormal accumulation of mutant NOTCH3, and CADASIL vascular smooth muscle cells have been found with autophagy-lysosomal dysfunction. However, whether plasma exosomes change in CADASIL patients is still unclear. OBJECTIVE: We are aimed to investigate the differences of plasma exosomes between CADASIL patients and healthy controls. METHODS: The subjects included 30 CADASIL patients and 30 healthy controls without NOTCH3 mutation. The severity of white matter lesions (WMLs) of CADASIL patients was quantified by Fazekas score. Transmission electron microscopy and nanoparticle tracking analysis were performed to characterize plasma exosomes. In addition, NOTCH3, Neurofilament light and Abeta42 levels in plasma exosomes were quantified by enzyme-linked immunosorbent assays. RESULTS: We found that exosomes from CADASIL patients were lower in quantity. In addition, CADASIL plasma exosomes had significantly lower levels of NOTCH3 and significantly increased levels of NFL than those of matched healthy subjects. Interestingly, plasma exosome NOTCH3 levels of CADASIL patients significantly correlated with severity of WMLs. CONCLUSION: The exosome NOTCH3 may be related to the pathological changes of CADASIL, which provides a basis for the pathogenesis research of CADASIL. In addition, plasma exosome NOTCH3 and NFL levels may act as biomarkers to monitor and predict disease progression and measure therapeutic effectiveness in the future clinical trials. | CADASIL |
Skin prick testing remains the most popular way to confirm an IgE-mediated allergic response. This study was performed to compare the accuracy and sensitivity of two skin testing modalities (serial endpoint titration and skin prick testing with 2 different in vitro assays). In 52 atopic patients serial endpoint titration showed a higher degree of sensitivity in evaluating skin response in less sensitive reactors. At higher degrees of reactivity in individual patients there was good correlation between the 3 modalities. Identifying patients who are less sensitive reactors is important, so that they can be started on immunotherapy. In fact, an informal survey of low-reacting patients treated with immunotherapy showed a high degree of success. | Skin Test End-Point Titration |
Wolfiporia cocos is a fungus containing triterpenoids and is widely used as an herbal medicine. However, it is unknown whether its main triterpenoid contents differ in different tissues. In this study, we identified dehydrotumulosic acid, polyporenic acid C, pachymic acid, dehydrotrametenolic acid, and dehydroeburicoic acid as the five main triterpenoids in W. cocos. We also systematically profiled the contents and distribution of these main triterpenoids in different tissues of W. cocos. High contents of all five triterpenoids were found in the surface layer of W. cocos. Intriguingly, we noted that the highest contents of the five triterpenoids were found in the surface layer of the sclerotium grown under pollution-controlled cultivation; the second-highest contents were found in the surface layer of the natural sclerotium. These results indicate that environmentally friendly cultivation of the sclerotium of W. cocos is a practical way to increase the productivity of W. cocos. In addition, our findings suggest that the triterpenoids may contribute to the pharmacological activity of W. cocos, and the surface layer of sclerotium in W. cocos might be a promising raw material for applications in health care and the development of functional medical products. | Lanosterol |
Mobile proton-containing solutes can be detected by MRI by the chemical exchange saturation transfer (CEST) method. CEST sensitivity is dramatically enhanced by using, as exchanging protons, the water molecules confined inside liposomes, shifted by a paramagnetic shift reagent. The chemical shift of the intraliposomal water resonance (delta(IL) ) is affected by the overall shape of the supramolecular system. delta(IL) of a spherical LipoCEST acts as a sensitive reporter of the distribution of streptavidin proteins anchored at the liposome surface by biotinylated phospholipids. This finding prompted the design of a MMP-2 responsive LipoCEST agent as the streptavidin moieties can be released from the liposome surfaces when a properly tailored enzyme-cleavable peptide is inserted on the phospholipids before the terminal biotin residues. delta(IL) reports on the overall changes in the supramolecular architecture associated to the cleavage carried out by MMP-2." | Proton Magnetic Resonance Spectroscopy |
BACKGROUND: Electronic Consultation (e-consults) can provide improved access, enhance patient and provider satisfaction, and reduce beneficiary travel expenses. We explored how e-consults were implemented across three specialty areas, diabetes (Diab), gastroenterology (GI), and neurosurgery (Neuro), at two Veterans Affairs hospitals in terms of strategies for use and time-lines. METHODS: We conducted observations and electronically shadowed patient e-consultations submitted to a specialty care service by primary care provider(s) at the two sites during a thirteen-month period. We divided the e-consult process in each specialty into three broad milestones; Request (from primary to specialty), Response (from specialty back to primary), and Follow up (from primary to patient), and recorded the flow and time in each category. An overall hierarchy of e-consults was developed to illustrate the many ways an e-consult was used. The Kolmogorov-Smirnov test was used to compare the distribution of time across specialties. RESULTS: A total of 394 consults submitted between April 14, 2012 and May 2, 2013 were reviewed (Diab=152, GI=169, Neuro=73). Of the 152 diabetes specialty clinic e-consults, 35% required some sort of direct contact with the patient by the specialty clinic before a recommendation was provided. Overall, 58% of the e-consults were completed within 20days, while 68% were completed within 30days. The Response times between Diab and GI were significantly different (median=0 vs. 3days; p<0.0001) and so were Follow up times (median=0 vs. 4days; p<0.0001). All three stages were statistically different between Diab and Neuro; however, there was not enough evidence to suggest any differences between GI and Neuro. CONCLUSIONS: The use of an e-consult is likely to vary based on the specialty, but the often significant variations in time may continue to hinder prompt access to care. E-consult design, implementation, documentation, training, self-learning, and monitoring should be tailored to get the most benefit out of this system. | Remote Consultation |
PURPOSE: To examine HMGA2 expression and investigate its clinical and prognostic significance in human urothelial bladder cancer (BUC). METHODS: We detected HMGA2 mRNA and protein expression by quantitative reverse-transcription polymerase chain reaction and western blotting, respectively in 44 frozen bladder cancer tissues and 18 adjacent normal bladder tissues. HMGA2 protein expression was assessed by immunohistochemical analysis of 148 paraffin-embedded specimens of human BUC and 30 specimens of adjacent normal bladder tissue. Correlations between HMGA2 and clinicopathologic features and prognosis were tested by statistical analyses. RESULTS: HMGA2 mRNA and protein levels in bladder cancer samples were significantly increased compared with adjacent normal bladder tissues (P < 0.001). mRNA overexpression correlated with high stage and grade of the bladder cancer (P < 0.001 and P = 0.002 respectively). HMGA2 protein expression was negative in all normal urothelial tissue samples, but positive in 52% (77/148) of bladder cancers (P < 0.001). HMGA2 expression correlated with tumor grade and stage (P < 0.001 and P = 0.003 respectively), Overexpression of HMGA2 protein in non-muscle-invasive bladder cancer was significantly associated with shorter recurrence-free survival (P < 0.001), and progression-free survival (P = 0.0004). Multivariate analysis showed that HMGA2 expression was an independent prognostic factor for both tumor recurrence (P < 0.001) and tumor progression (P = 0.006). CONCLUSIONS: HMGA2 is up-regulated in bladder cancer at both the transcriptional and translational levels compared with normal bladder tissue, HMGA2 protein is thus a potential prognostic marker for predicting tumor recurrence and progression. | HMGA2 Protein |
The asymmetric bioreduction of a library of beta-cyanoacrylate esters using ene-reductases was studied with the aim to provide a biocatalytic route to precursors for GABA analogues, such as pregabalin. The stereochemical outcome could be controlled by substrate-engineering through size-variation of the ester moiety and by employing stereochemically pure (E)- or (Z)-isomers, which allowed to access both enantiomers of each product in up to quantitative conversion in enantiomerically pure form. In addition, stereoselectivities and conversions could be improved by mutant variants of OPR1, and the utility of the system was demonstrated by preparative-scale applications. | Aminobutyrates |
Ichthyosis bullosa of Siemens (IBS) is a rare disorder of cornification characterized by blister formation in the upper suprabasal layers of the epidermis. Molecular analysis of IBS has identified mutations in the keratin 2e (K2e) gene, which is located in the type II keratin gene cluster on chromosome 12q. We have studied two IBS families and have identified heterozygous point mutations in codon 493 of the K2e gene in both families. Whereas a non-conservative amino acid substitution at position 117 of the 2B region of K2e (E117K) was associated with a severe phenotype in family 1, family 2 showed mild clinical features as a result of a conservative substitution (E117D). These data suggest a phenotype-genotype correlation in these families. | Keratin-2 |
PURPOSE: To evaluate the accuracy and biological basis for [(11)C]choline-PET-CT in the nodal staging of high risk localized prostate cancer patients. EXPERIMENTAL DESIGN: Twenty-eight patients underwent dynamic [(11)C]choline-PET-CT of the pelvis and lower abdomen prior to extended laparoscopic pelvic lymph node dissection (eLPL). The sensitivity and specificity of [(11)C]choline PET, [(11)C]choline PET-CT, and MRI for nodal detection were calculated. Average and maximal standardized uptake values (SUV(ave), SUV(max)) were compared with choline kinase alpha (CHKalpha) and Ki67 immunohistochemistry scores. RESULTS: Four hundred and six lymph nodes (LN), in 26 patients, were assessable. Twenty-seven (6.7%) involved pelvic nodes at eLPL were detected in 9 patients. Seventeen of the 27 involved nodes were subcentimeter. The sensitivity and specificity on a per nodal basis were 18.5% and 98.7%, 40.7% and 98.4%, and 51.9% and 98.4% for MRI, [(11)C]choline PET, and [(11)C]choline PET-CT, respectively. Sensitivity was higher for [(11)C]choline PET-CT compared with MRI (P = 0.007). A higher nodal detection rate, including subcentimeter nodes, was seen with [(11)C]choline PET-CT than MRI. Malignant lesions showed CHKalpha expression in both cytoplasm and nucleus. SUV(ave) and SUV(max) strongly correlated with CHKalpha staining intensity (r = 0.68, P < 0.0001 and r = 0.63, P = 0.0004, respectively). In contrast, Ki67 expression was generally low in all tumors. CONCLUSION: This study establishes the relationship between [(11)C]choline PET-CT uptake with choline kinase expression in prostate cancer and allows it to be used as a noninvasive means of staging pelvic LNs, being highly specific and more sensitive than MRI, including the detection of subcentimeter disease. | Choline Kinase |
Wheezing in children often is the result of asthma, but vocal cord dysfunction (VCD) may cause stridor or sounds that sometimes are misattributed to the wheezing of asthma. The frequent comorbidity of asthma and VCD also adds to the difficulty in making a clear diagnosis. The challenges of evaluating and treating wheezing are complicated further in children with developmental disorders, such as autism, because of the difficulties of obtaining an adequate history and assessing the clinical response to treatment. This article presents a patient with multiple psychiatric problems, including autism, with severe recurrent wheezing as a result of vocal cord dysfunction and asthma. Hypnosis has previously proven efficacious for treating vocal cord dysfunction, and in this case, hypnotic techniques were major factors in successful symptom control. | Vocal Cord Dysfunction |
Critical coronary stenoses have been shown to contribute to only a minority of acute coronary syndromes (ACS) and sudden cardiac death. Autopsy studies have identified a subgroup of high-risk patients with disrupted vulnerable plaque and modest stenosis. Consequently, a clinical need exists to develop methods to identify these plaques prospectively before disruption and clinical expression of disease. Recent advances in invasive and noninvasive imaging techniques have shown the potential to identify these high-risk plaques. The anatomical characteristics of the vulnerable plaque such as thin cap fibroatheroma and lipid pool can be identified with angioscopy, high frequency intravascular ultrasound, intravascular MRI, and optical coherence tomography. Efforts have also been made to recognize active inflammation in high-risk plaques using intravascular thermography. Plaque chemical composition by measuring electromagnetic radiation using spectroscopy is also an emerging technology to detect vulnerable plaques. Noninvasive imaging with MRI, CT, and PET also holds the potential to differentiate between low and high-risk plaques. However, at present none of these imaging modalities are able to detect vulnerable plaque neither has been shown to definitively predict outcome. Nevertheless in contrast, there has been a parallel development in the physiological assessment of advanced atherosclerotic coronary artery disease. Thus recent trials using fractional flow reserve in patients with modest non flow-limiting stenoses have shown that deferral of PCI with optimal medical therapy in these patients is superior to coronary intervention. Further trials are needed to provide more information regarding the natural history of high-risk but non flow-limiting plaque to establish patient-specific targeted therapy and to refine plaque stabilizing strategies in the future. | Coronary Stenosis |
RATIONALE: Jacobsen syndrome is a rare chromosomal disorder caused by deletions in the long arm of human chromosome 11, resulting in multiple developmental defects including congenital heart defects. Combined studies in humans and genetically engineered mice implicate that loss of ETS1 (E26 transformation specific 1) is the cause of congenital heart defects in Jacobsen syndrome, but the underlying molecular and cellular mechanisms are unknown. OBJECTIVE: To determine the role of ETS1 in heart development, specifically its roles in coronary endothelium and endocardium and the mechanisms by which loss of ETS1 causes coronary vascular defects and ventricular noncompaction. METHODS AND RESULTS: ETS1 global and endothelial-specific knockout mice were used. Phenotypic assessments, RNA sequencing, and chromatin immunoprecipitation analysis were performed together with expression analysis, immunofluorescence and RNAscope in situ hybridization to uncover phenotypic and transcriptomic changes in response to loss of ETS1. Loss of ETS1 in endothelial cells causes ventricular noncompaction, reproducing the phenotype arising from global deletion of ETS1. Endothelial-specific deletion of ETS1 decreased the levels of Alk1 (activin receptor-like kinase 1), Cldn5 (claudin 5), Sox18 (SRY-box transcription factor 18), Robo4 (roundabout guidance receptor 4), Esm1 (endothelial cell specific molecule 1) and Kdr (kinase insert domain receptor), 6 important angiogenesis-relevant genes in endothelial cells, causing a coronary vasculature developmental defect in association with decreased compact zone cardiomyocyte proliferation. Downregulation of ALK1 expression in endocardium due to the loss of ETS1, along with the upregulation of TGF (transforming growth factor)-beta1 and TGF-beta3, occurred with increased TGFBR2/TGFBR1/SMAD2 signaling and increased extracellular matrix expression in the trabecular layer, in association with increased trabecular cardiomyocyte proliferation. CONCLUSIONS: These results demonstrate the importance of endothelial and endocardial ETS1 in cardiac development. Delineation of the gene regulatory network involving ETS1 in heart development will enhance our understanding of the molecular mechanisms underlying ventricular and coronary vascular developmental defects and will lead to improved approaches for the treatment of patients with congenital heart disease." | Jacobsen Distal 11q Deletion Syndrome |
Mucolipidosis-IIIgamma (ML-IIIgamma) is a recessively inherited slowly progressive skeletal dysplasia caused by mutations in GNPTG. We report the genetic and clinical findings in the largest cohort with ML-IIIgamma so far: 18 affected individuals from 12 families including 12 patients from India, five from Turkey, and one from the USA. With consanguinity confirmed in eight of 12 families, molecular characterization showed that all affected patients had homozygous pathogenic GNPTG genotypes, underscoring the rarity of the disorder. Unlike ML-IIIalphabeta, which present with a broader spectrum of severity, the ML-III gamma phenotype is milder, with onset in early school age, but nonetheless thus far considered phenotypically not differentiable from ML-IIIalphabeta. Evaluation of this cohort has yielded phenotypic findings including hypertrophy of the forearms and restricted supination as clues for ML-IIIgamma, facilitating an earlier correct choice of genotype screening. Early identification of this disorder may help in offering a timely intervention for the relief of carpal tunnel syndrome, monitoring and surgery for cardiac valve involvement, and evaluation of the need for joint replacement. As this condition may be confused with rheumatoid arthritis, confirmation of diagnosis will prevent inappropriate use of immunosuppressants and disease-modifying agents. | Mucolipidoses |
A new flavonoid named saniculamin C (1), together with six known compounds (2-7), were isolated from the whole plants of Sanicula lamelligera Hance. The chemical structures were elucidated by spectroscopic and physico-chemical analyses. All isolates were evaluated for in vitro cytotoxic activities against four human cancer cell lines, HepG2, SGC-7901 gastric cancer, Hela and A-549 lung cancer. Compound 1 showed potent antiproliferative activities against SGC-7901 cells with IC(50) value of 7.45 muM. In addition, compound 6 exhibited weak antiproliferative activities against HepG2, SGC-7901, Hela cancer cells with IC(50) values of 10.43, 8.24 and 15.32 muM, respectively.[Formula: see text]. | Sanicula |
The findings in this clinical, longitudinal study describe the process of attachment and autonomy as it unfolds during the latency period of development. Ten normal boys and girls were studied from ages six through eleven. A separate timetable of latency development for boys and girls is suggested. The differences in the boys' and girls' separation responses, which include feelings of a lack of self-coherence, loss, anger, neediness, movement toward peers and defense functioning, are delineated and discussed. | Latency Period, Psychological |
How quickly do you turn around STAT" laboratory requests? Do delays in processing STATS cause delays in deciding patient treatment protocols? Do these delays increase your patient's length of stay? The authors describe a situation in which morning STATS were delayed because of a large volume of patient requests. This article looks at the use of continuous quality improvement tools to improve this persistent laboratory problem. It explains FOCUS-PDCA, the method, and describes its application to reduce total STAT requests from 37% to 27% and to improve their turnaround time by 67%." | Laboratories, Hospital |
The literature strongly suggests that daily physical activity is genetically and biologically regulated. Potential identities of the responsible mechanisms are unclear, but little has been written concerning the possible evolutionary selection pressures leading to the development of genetic/biological controls of physical activity. Given the weak relationship between exercise endurance and activity levels and the differential genomic locations associated with the regulation of endurance and activity, it is probable that regulation of endurance and activity evolved separately. This hypothesis paper considers energy expenditures and duration of activity in hunter/gatherers, pretechnology farmers, and modern Western societies and considers the potential of each to selectively influence the development of activity regulation. Food availability is also considered given the known linkage of caloric restriction on physical activity as well as early data relating food oversupply to physical inactivity. Elucidating the selection pressures responsible for the genetic/biological control of activity will allow further consideration of these pressures on activity in today's society, especially the linkages between food and activity. Further, current food abundance is removing the cues for activity that were present for the first 40,000 years of human evolution, and thus future research should investigate the effects of this abundance upon the mechanisms regulating activity. | Selection, Genetic |
The infection of melon plants by Melon necrotic spot virus (MNSV) and the development of necrotic disease symptoms are a seasonal occurrence in Japan, which take place between winter and early summer, but not during mid-summer. In this paper we investigate the effect of three different temperatures (15, 20, and 25 degrees C) on the local and systemic expression of MNSV in melon plants. Previously, the incidence of plants expressing systemic symptoms caused by MNSV and other viruses was found to be greater at temperatures less than 20 degrees C. In this study, our temperature-shift experiments support previous studies that found the expression of systemic symptoms increases as temperature falls from 25 to 20 degrees C and decreases as temperature rises from 20 to 25 degrees C. However, MNSV replication in melon cells and local viral movement within leaves following the inoculation of melon protoplasts or cotyledons were more frequent at 25 degrees C than at 15 or 20 degrees C. | Carmovirus |
Life stress is central to many contemporary theories of human health and behavior. Despite this fact, numerous conceptual and measurement issues remain unresolved. The present article explores these topics by first summarizing several key definitional and conceptual matters that are important for life stress research. Second, I introduce stressnology, defined herein as the fictitiously named, but otherwise very real and problematic approach to studying life stress exposure that involves measuring only the superficial contours of this very complex construct. Finally, I review some recent methodological advancements that have the potential to move us past primitive approaches to conceptualizing and assessing life stress. Ultimately, although the influence that life stress has on human health and behavior is profound, our understanding of this construct-and how it affects wellbeing, functioning, and development-is still very limited. Using state-of-the-art instruments for assessing life stress exposure, especially across the entire life course, should therefore be a top scientific and clinical priority. | Benchmarking |
Private practice, a sector which attracts male nurses. Although the proportion of women and men within the nursing profession remains stable, the representation of male nurses in private practice has been increasing steadily since 2002 which raises certain questions. This article attempts to explain this phenomenon. | Nurses, Male |
Polysaccharide K (PSK) is a biological response modifier used for adjuvant immunotherapy of malignant diseases. We studied the potential applicability of PSK for preventing tumor progression using an experimental model of murine lymphoma. Mice inoculated with the radiation leukemia virus (RadLV) develop thymic lymphomas after a latency of 3-6 months. However, 2 weeks after virus inoculation, prelymphoma cells can already be detected in the thymus. We found that PSK treatment induced hyperresponsiveness to concanavalin A and heightened production of interleukin-2 (IL-2) and IL-4 in spleen cells of both control and prelymphoma mice. The response was transient and was accompanied with a dominant usage of T cells expressing V beta 8, but other T cell subsets were also stimulated by PSK. T lymphoma cells expressing V beta 8.2 underwent apoptosis when incubated with PSK. Treatment of RadLV-inoculated mice with PSK delayed the onset of overt lymphoma (and mortality) but could not protect the mice from the disease. Combined treatment with PSK and a RadLV-specific immunotoxin prevented synergistically the progression of the prelymphoma cells to frank lymphoma. The results suggest that PSK contains a superantigen-like component that selectively activates V beta 8+ T cells. Its administration prelymphoma mice interfered with the process of lymphoma progression. | Radiation Leukemia Virus |
Hepatic macrophages are a remarkably heterogeneous population consisting of self-renewing tissue-resident phagocytes, termed Kupffer cells (KCs), and recruited macrophages derived from peritoneal cavity as well as the bone marrow. KCs are located in the liver sinusoid where they scavenge the microbe from the portal vein to maintain liver homeostasis. Liver injury may trigger hepatic recruitment of peritoneal macrophages and monocyte-derived macrophages. Studies describing macrophage accumulation have shown that hepatic macrophages are involved in the initiation and progression of various liver diseases. They act as tolerogenic antigen-presenting cells to inhibit T-cell activation by producing distinct sets of cytokines, chemokines, and mediators to maintain or resolve inflammation. Furthermore, by releasing regenerative growth factors, matrix metalloproteinase arginase, they promote tissue repair. Recent experiments found that KCs and recruited macrophages may play different roles in the development of liver disease. Given that hepatic macrophages are considerably plastic populations, their phenotypes and functions are likely switching along disease progression. In this review, we summarize current knowledge about the role of tissue-resident macrophages and recruited macrophages in pathogenesis of alcoholic liver disease (ALD), non-alcoholic steatohepatitis (NASH), viral hepatitis, and hepatocellular carcinoma (HCC). | Kupffer Cells |
The global coronavirus disease 2019 (COVID-19) pandemic spurred an urgent need for vaccination and herd immunity. Recently, mRNA vaccines for COVID-19 have been used widely despite reports of several adverse events. Most adverse effects are mild, although a few are associated with neurological complications. Unfortunately, there is a scarcity of information on peripheral nerve complications after COVID-19 mRNA vaccination. We report the case of an immunocompetent young male patient who suffered from ipsilateral wrist drop with multiple lymphadenopathy in the cervical and axillary region after Pfizer-BioNTech vaccination. He experienced unilateral wrist drop, which significantly improved with corticosteroid treatment. Based on knowledge of this adverse effect, careful surveillance and increased awareness are needed for early diagnosis. To the best of our knowledge, this is the first reported case in the English literature of radial neuropathy resulting in wrist drop in a recently vaccinated and young immunocompetent patient. | Radial Neuropathy |
Surname distribution can be a useful tool for studying the genetic structure of a human population. In South America, the Uruguay population has traditionally been considered to be of European ancestry, despite its trihybrid origin, as proved through genetics. The aim of this study was to investigate the structure of the Uruguayan population, resulting from population movements and surname drift in the country. The distribution of the surnames of 2,501,774 people on the electoral register was studied in the nineteen departments of Uruguay. Multivariate approaches were used to estimate isonymic parameters. Isolation by Distance was measured by correlating isonymic and geographic distances. In the study sample, the most frequent surnames were consistently Spanish, reflecting the fact that the first immigration waves occurred before Uruguayan independence. Only a few surnames of Native origin were recorded. The effective surname number (alpha) for the entire country was 302, and the average for departments was 235.8 +/- 19. Inbreeding estimates were lower in the south-west of the country and in the densely populated Montevideo area. Isonymic distances between departments were significantly correlated with linear geographic distance (p < 0.001) indicating continuously increasing surname distances up to 400 km. Surnames form clusters related to geographic regions affected by different historical processes. The isonymic structure of Uruguay shows a radiation towards the east and north, with short-range migration playing a major role, while the contribution of drift, considering the small variance of alpha, appears to be minor. | Genetics, Population |
New polyomaviruses are continually being identified, and it is likely that links between this virus family and disease will continue to emerge. Unfortunately, a specific treatment for polyomavirus-associated disease is lacking. Because polyomaviruses express large Tumor Antigen, TAg, we hypothesized that small molecule inhibitors of the essential ATPase activity of TAg would inhibit viral replication. Using a new screening platform, we identified inhibitors of TAg's ATPase activity. Lead compounds were moved into a secondary assay, and ultimately two FDA approved compounds, bithionol and hexachlorophene, were identified as the most potent TAg inhibitors known to date. Both compounds inhibited Simian Virus 40 replication as assessed by plaque assay and quantitative PCR. Moreover, these compounds inhibited BK virus, which causes BKV Associated Nephropathy. In neither case was host cell viability compromised at these concentrations. Our data indicate that directed screening for TAg inhibitors is a viable method to identify polyomavirus inhibitors, and that bithionol and hexachlorophene represent lead compounds that may be further modified and/or ultimately used to combat diseases associated with polyomavirus infection. | BK Virus |
IL-17 plays an important role in host defense and autoimmunity via the induction of proinflammatory gene expression, particularly in combination with TNF-alpha. The molecular mechanisms by which IL-17 regulates such expression are not well understood. Using the mouse chemokine CXCL1 (KC) gene as a model, we have examined the effects of IL-17 alone or in combination with TNF-alpha on transcriptional and posttranscriptional events. Although treatment of mouse embryonic fibroblasts with IL-17 alone only modestly increased KC expression, the combination of IL-17 with TNF-alpha induced a synergistic response. IL-17 treatment exerted a strong posttranscriptional effect by extending the t1/2 of the highly unstable, TNF-alpha-induced KC mRNA. Using a tetracycline-regulated transgene in HeLa cells, we determined that IL-17 treatment alone promoted stabilization of KC mRNA in the absence of TNF-alpha. IL-17 treatment exerted little effect on KC transcription or NF-kappaB activation, suggesting that it primarily acts posttranscriptionally. We identified a number of other mRNAs whose t1/2 are prolonged in response to IL-17, suggesting that this is a common mechanism by which IL-17 promotes enhanced gene expression. Finally, activator of NF-kappaB1 protein (Act1), an adaptor protein recently implicated in IL-17 signaling, was necessary for IL-17-induced stabilization, and overexpression of Act1 resulted in stabilization of KC mRNA, indicating that events downstream of Act1 are sufficient to initiate this process. Thus, the synergy between TNF-alpha and IL-17 reflects their independent actions on KC gene expression; TNF-alpha serves as a stimulus to initiate transcription through activation of NF-kappaB, whereas IL-17 drives mRNA stabilization through an Act1-dependent pathway. | Chemokines, CXC |
We have studied the levels of glutathione S-transferase in drug-resistant and -sensitive human tumor cell lines to examine a possible involvement of glutathione S-transferase (GST) in multidrug resistance mechanisms. No increase in the activity of glutathione S-transferase was detected in myelogenous leukemia K562 resistant to adriamycin (K562/ADM), ovarian carcinoma cell line A2780 resistant to adriamycin (2780AD), or acute lymphoblastic leukemia cell line CCRF-CEM resistant to vinblastine (CEM-VLB100), compared with the drug-sensitive parent tumor cells. The human breast cancer cell lines Hattori and MCF-7 had a 12- to 63-fold lower level of glutathione S-transferase activity than K562, A2780, CCRF-CEM, and their drug-resistant sublines. Induction of ADM resistance in Hattori did not increase the activity of glutathione S-transferase. However, induction of colchicine resistance in MCF-7 resulted in a 70-fold increase in the activity of glutathione S-transferase. A revertant of the colchicine-resistant MCF-7 contained a level of glutathione S-transferase activity similar to that of the resistant subline. The increase of glutathione S-transferase activity did not alter the sensitivity of the cell to cytotoxic drugs. The increased activity was due to the appearance of glutathione S-transferase pi, as shown by enzyme inhibition using anti-glutathione S-transferase pi antibody. Our findings indicate that increased cellular glutathione S-transferase activity is not associated with the development of multidrug resistance. | Glutathione Transferase |
Platycodon grandiflorus (balloon flower), used as a food reserve as well as in traditional herbal medicine, is known for its multiple beneficial effects. In particular, this plant is widely used as a vegetable in Republic of Korea. We examined the ameliorative effects of P. grandiflorus on alloxan-induced pancreatic islet damage in zebrafish. The aerial part treatment led to a significant recovery in pancreatic islet size and glucose uptake. The efficacy of the aerial part was more potent than that of the root. Eight flavonoids (1-8) were isolated from the aerial part. Structures of two new flavone glycosides, designated dorajiside I (1) and II (2), were elucidated to be luteolin 7-O-alpha-L-rhamno-pyranosyl (1 --> 2)-(6-O-acetyl)-beta-D-glucopyranoside and apigenin 7-O-alpha-L-rhamnopyranosyl (1 --> 2)-(6-O-acetyl)-beta-D-glucopyranoside, respectively, by spectroscopic analysis. Compounds 1, 3, 4 and 6-8 yielded the recovery of injured pancreatic islets in zebrafish. Among them, compound 7 blocked K(ATP) channels in pancreatic beta-cells. Furthermore, compounds 3, 4, 6 and 7 showed significant changes with respect to the mRNA expression of GCK, GCKR, GLIS3 and CDKN2B compared to alloxan-induced zebrafish. In conclusion, the aerial part of P. grandiflorus and its constituents conferred a regenerative effect on injured pancreatic islets. | Alloxan |
Exposure to a new wood preservative agent (Sinesto B), whose active ingredient is 2-ethylhexanoic acid (2-EHA), was determined by urinalysis of the parent chemical and its metabolites in workers employed in four Finnish sawmills. The excretion of these chemicals was compared with the inhaled dose analyzed in air samples collected at the breathing zone and with the percutaneous absorption determined by epicutaneous sampling. The main route for entrance of 2-EHA into the body is by breathing, because the urinary concentration of 2-EHA correlated linearly with the concentration of 2-EHA in the air (r = 0.70). There was no correlation between skin contamination and urinary levels of 2-EHA. In most cases the highest urinary concentrations of 2-EHA were found immediately after the work shift. Therefore, in order to evaluate a worker's exposure, the urine sample has to be taken immediately after the work shift. Workers in cranes had the highest exposure to 2-EHA, which describes well the evaporation of Sinesto B into the ambient air. 2-EHA was not found in the urine of non-exposed workers. | Caproates |
1. The fate of N-methyl-N'-(hydroxy[14C]methyl)thiourea (MHT) has been studied in the male Sprague-Dawley rat. The compound is degraded to N-methylthiourea and formaldehyde. 2. N-Methylthiourea is excreted as a urinary metabolite whereas the formaldehyde is not excreted, either in the urine or the expired air, but is metabolized via formate to CO2. 3. At least 50% of an i.p. dose (100 mg/kg) of MHT is excreted unchanged and some of this undergoes hydrolysis within the urine to N-methylthiourea and formaldehyde. Production of formaldehyde leads to the formation of the urinary artefact N-(hydroxymethyl)urea. 4. Tissue-distribution studies with 14C-MHT have shown that radioactivity is selectively associated with the thyroid gland. A preliminary investigation has indicated that MHT has anti-thyroid hormone activity as it lowers the thyroxine in rat serum. | Noxythiolin |
Some people react to smells or chemicals at levels far below toxicological thresholds with nonspecific symptoms, fear and social isolation. They may be diagnosed with multiple chemical sensitivity. There is no empirical evidence indicating that this condition is explained by toxicological mechanisms, even though a number of theories have been proposed. The authors of this review conclude that this is a functional condition. These patients need information and treatment in accordance with this fact. Instead of being advised how to avoid exposure to chemicals, they should be properly trained in appropriate confrontation with the chemicals encountered in everyday life. | Environmental Illness |
Elevated temperature is a major abiotic stress limiting the growth of cool-season grasses during the summer months. The objectives of this study were to determine the genetic variation in the expression patterns of selected genes involved in several major metabolic pathways regulating heat tolerance for two genotypes contrasting in heat tolerance to confirm their status as potential candidate genes, and to identify PCR-based markers associated with candidate genes related to heat tolerance in a colonial (Agrostis capillaris L.) x creeping bentgrass (Agrostis stolonifera L.) hybrid backcross population. Plants were subjected to heat stress in controlled-environmental growth chambers for phenotypic evaluation and determination of genetic variation in candidate gene expression. Molecular markers were developed for genes involved in protein degradation (cysteine protease), antioxidant defense (catalase and glutathione-S-transferase), energy metabolism (glyceraldehyde-3-phosphate dehydrogenase), cell expansion (expansin), and stress protection (heat shock proteins HSP26, HSP70, and HSP101). Kruskal-Wallis analysis, a commonly used non-parametric test used to compare population individuals with or without the gene marker, found the physiological traits of chlorophyll content, electrolyte leakage, normalized difference vegetative index, and turf quality were associated with all candidate gene markers with the exception of HSP101. Differential gene expression was frequently found for the tested candidate genes. The development of candidate gene markers for important heat tolerance genes may allow for the development of new cultivars with increased abiotic stress tolerance using marker-assisted selection. | Agrostis |
PURPOSE: To report acute toxicity resulting from radiotherapy (RT) dose escalation and hypofractionation using intensity-modulated RT (IMRT) treatment combined with androgen suppression in high-risk prostate cancer patients. METHODS AND MATERIALS: Sixty patients with a histological diagnosis of high-risk prostatic adenocarcinoma (having either a clinical Stage of > or =T3a or an initial prostate-specific antigen [PSA] level of > or =20 ng/ml or a Gleason score of 8 to 10 or a combination of a PSA concentration of >15 ng/ml and a Gleason score of 7) were enrolled. RT prescription was 68 Gy in 25 fractions (2.72 Gy/fraction) over 5 weeks to the prostate and proximal seminal vesicles. The pelvic lymph nodes and distal seminal vesicles concurrently received 45 Gy in 25 fractions. The patients were treated with helical TomoTherapy-based IMRT and underwent daily megavoltage CT image-guided verification prior to each treatment. Acute toxicity scores were recorded weekly during RT and at 3 months post-RT, using Radiation Therapy Oncology Group acute toxicity scales. RESULTS: All patients completed RT and follow up for 3 months. The maximum acute toxicity scores were as follows: 21 (35%) patients had Grade 2 gastrointestinal (GI) toxicity; 4 (6.67%) patients had Grade 3 genitourinary (GU) toxicity; and 30 (33.33%) patients had Grade 2 GU toxicity. These toxicity scores were reduced after RT; there were only 8 (13.6%) patients with Grade 1 GI toxicity, 11 (18.97%) with Grade 1 GU toxicity, and 5 (8.62%) with Grade 2 GU toxicity at 3 months follow up. Only the V60 to the rectum correlated with the GI toxicity. CONCLUSION: Dose escalation using a hypofractionated schedule to the prostate with concurrent pelvic lymph node RT and long-term androgen suppression therapy is well tolerated acutely. Longer follow up for outcome and late toxicity is required. | Lymphatic Irradiation |
PURPOSE OF REVIEW: To review the anesthestic and airway management for gastrointestinal procedures outside of the operating room. RECENT FINDINGS: The number of gastrointestinal endoscopic procedures performed is steadily increasing worldwide. As complexity, duration and invasiveness of procedures increase, there is ever greater requirement for deeper sedation or general anesthesia. A close relationship between anesthetic practitioners and endoscopists is required to ensure safe and successful outcomes. The American Society of Gastrointestinal endoscopy and the British Society of Gastroenterology have recently released guidelines for sedation and general anesthesia in gastrointestinal endoscopy, highlighting the need for careful monitoring for all cases, and anesthetic expertise in complex cases. The recent advances in high-flow nasal oxygenation in sedation may provide alternative options for oxygenation during gastrointestinal sedation, especially in deep sedation and this may reduce the need for general anesthesia. SUMMARY: The advances in gastrointestinal endoscopic intervention have increased the requirement for deep sedation and anesthetic involvement outside of the operating room. Careful titration of anesthetic intervention and close monitoring are required to ensure patient safety. | Pain, Procedural |
A study of 1000 cases of septic endocarditis served as a basis for an analysis of the natural history of the diseases (1939-1972): changes in its etiology, clinical course and therapy. The increasing frequency of hospital infection (endocarditis) is emphasized. The characteristics of Staphylococcal and fungal endocarditis are presented, those of the lesion developing on heart valve prostheses as well. The classification of septic endocarditis is analysed, the stages of its activeness are described (III, II, I) along with the clinical and laboratory signs. Schemes of etiotropic therapy are presented, as well as rational combinations of antibiotics. The role of surgery in the management of primary septic endocarditis is described, and the rationale of preventive employment of antibiotics is discussed. | Endocarditis |
BACKGROUND: Persistent pulmonary hypertension of the newborn is a clinical syndrome caused by failure in the transition from fetal to neonatal circulation either to achieve or to maintain low pulmonary vascular resistance after birth. The syndrome is a complex condition associated with different cardiopulmonary disorders. METHODS: This article presents a review of the literature and the author's own experience regarding the fetal circulation, the transition to the newborn circulation, and the mechanical and molecular regulatory factors, including a discussion of the pathophysiology, aetiology, diagnostics and main goal of treatment for persistent pulmonary hypertension of the newborn. RESULTS: The pathophysiology of persistent pulmonary hypertension is characterised by high pulmonary vascular resistance and high pulmonary artery pressure. The blood is shunted from the right to the left circuit through the foramen ovale, ductus arteriosus and also by intrapulmonal shunts. The aetiologies can be classified as underdevelopment, maldevelopment and maladaptation of the pulmonary vasculature. The clinical signs are hypoxaemia, higher oxygenation tension and saturation in the upper rather than the lower limbs, respiratory failure, systemic hypotension and systolic cardiac murmur. The differential diagnoses are primarily serious lung disorders without persistent pulmonary hypertension, and congenital cyanotic heart defects. The diagnostic investigations are blood gas analysis, X-ray of the lung, and Doppler echocardiographic examination of the heart. INTERPRETATION: The main treatment goal is good oxygenation, pH in upper normal and pCO2 in lower normal levels. Positive pressure ventilation, sedation, NO gas inhalation and supporting treatment of the systemic blood pressure are usually necessary. Extracorporeal membrane oxygenation is considered as a last option." | Persistent Fetal Circulation Syndrome |
BACKGROUND: This study will assess the efficacy and safety of arthroscopic capsular release (ACR) for the treatment of post-stroke frozen shoulder (PSFS). METHODS: We will carry out a systematic study of randomized controlled trials that assess the efficacy and safety of ACR for PSFS. We will search all potential records for any eligible trials from selected electronic databases (MEDLINE, EMBASE, Cochrane Library, Web of Science, Chinese Biomedical Literature Database, WANGFANG, and China National Knowledge Infrastructure) and grey literature sources from inception to the present. Two authors will independently perform study selection, data extraction, and study quality assessment. Any disagreement will be solved by a third author via consultation. Statistical analysis will be carried out by RevMan 5.3 software. RESULTS: This study will comprehensively summarize current eligible studies to systematically assess the efficacy and safety of ACR for PSFS. CONCLUSION: This study will provide evidence to determine whether ACR is an effective management for patients with PSFS. | Bursitis |
In the United States (US), immigrants constitute a considerable and growing proportion of the general population. Compared to the US-born, immigrants have differential health risks, and it is unclear if environmental exposures contribute. In this work, we estimated disparities between immigrants and the US-born in fine particulate matter (PM(2.5)) exposure and attributable premature mortality, including by region of origin and time since immigration. With PM(2.5) estimates from a validated model at ~1 km(2) spatial resolution and residential Census tract population data, we calculated the annual area-weighted average PM(2.5) exposure for immigrants overall, the US-born, and immigrants separately by geographic region of origin and time since immigration. We then calculated the premature mortality attributed to PM(2.5) for each population group, assessing disparities by immigrant status in PM(2.5) exposure and attributable premature mortality in the US as a whole and in each US county to evevaluate spatial heterogeneity. Overall, immigrants were exposed to slightly higher PM(2.5) (0.36 mug/m(3), 3.8%) than the US-born. This exposure difference translates to 2.11 more premature deaths attributable to PM(2.5) per 100,000 in population for immigrants compared to the US-born in 2010. Immigrant - US-born disparities in PM(2.5) and attributable premature mortality were more severe among immigrants originating from Asia, Africa, and Latin America than those from Europe, Oceania, and North America. Disparities between immigrant groups by time since immigration were comparatively small. Sensitivity analyses using 2000 data and a non-linear set of PM(2.5) attributable mortality coefficients identified similar patterns. Our findings suggest that environmental exposure disparities, such as in PM(2.5), may contribute to immigrant health disparities in the US. | Mortality, Premature |
Combined modality therapy emerged from preclinical data showing that carefully chosen drugs could enhance the sensitivity of tumor cells to radiation while having nonoverlapping toxicities. Recent advances in molecular biology involving the identification of cellular receptors, enzymes, and pathways involved in tumor growth and immortality have resulted in the development of biologically targeted drugs. This review highlights the recent clinical data in support of newer generation cytotoxic chemotherapies and systemic targeted agents in combination with radiation therapy. | Radiation-Sensitizing Agents |
Three lichen secondary metabolites atranorin (1), evernic acid (2), and usnic acid (3), were evaluated for their in vitro clastogenic and antiproliferative effects on human lymphocytes using the cytochalasin-B blocked micronucleus (CBMN) assay at concentrations of 2 microg/mL, 4 microg/mL and 6 microg/mL of final culture solution. The frequency of micronucleus (MN) was scored in binucleated cells, and cytokinesis-block proliferation index (CBPI) was calculated. Among the tested compounds, 3 exhibited the most prominent effect decreasing the frequency of MN in the range of 42.5% - 48.9%, that is about double of the positive control amifostin WR-2721 that reduces MN frequency for 22.0%. The effect of evernic acid was approximately equal to action of amifostin (23.2% -32.9%). Atranorin at concentrations of 2 microg/mL and 4 microg/mL decreasing the frequency of MN only for 11.1% and 1.8%, while in concentration of 6 microg/mL increases the frequency of MN for 9.6 %. The comparable CBPI values of the investigated compounds and control suggested that they did not show a statistically significant inhibitory effect on lymphocyte cell proliferation at applied concentrations. | Hydroxybenzoates |
Six cholic acid derivatives (1-6) were isolated from broth cultures of Bacillus amyloliquefaciens UWI-W23, an isolate from the Trinidad Pitch Lake. The compounds were extracted via solvent extraction and/or XAD resin adsorption and purified using silica gel column chromatography. Their structures were elucidated using 1D, 2D NMR and ESI-MS spectrometry and FT-IR spectrophotometry. One of the compounds, taurodeoxycholate (2) is for the first time being reported from a bacterial source while deoxycholate (4) is for the first time being reported from a Gram-positive bacterium. The other compounds have not been previously isolated from Bacillus spp. viz. cholate (1), taurocholic acid (3); glycodeoxycholic acid (5) and glycocholic acid (6). All six compounds exhibited antimicrobial activity against P. aeruginosa and B. cereus with MICs ranging from 7 to 250â¯microg/mL. Cholate (1) also showed activity against MRSA (MICsâ¯=â¯125â¯microg/mL) and glycocholic acid (6) against S. cerevisiae (MICsâ¯=â¯15.6â¯microg/mL). | Cholic Acid |
Olive oil is the principal source of fat in the Mediterranean diet, which has been associated with a lower incidence of coronary heart disease and certain cancers. Olive oil is characterized by a high proportion of monounsaturated oleic acid, but the main peculiarity of extra-virgin oil is the presence of remarkable quantities of phenolic compounds, notably hydroxytyrosol and oleuropein, that provide high stability and strong taste. Recently, several studies have demonstrated that olive oil phenolics are powerful antioxidants, both in vitro and in vivo, and exert additional potent biologic activities that could partially account for the observed cardioprotective effects of the Mediterranean diet. | Diet, Atherogenic |
Penetrating corneal homografts were performed in albino rabbits. The experimental group received grafts soaked in a solution of concanavalin A; the control group received grafts soaked in lactated Ringer's solution. Animals with technically successful grafts were subsequently exposed to an additional antigenic stimulus from the corneal donor via skin grafting. This procedure produces a uniformly high rate of corneal graft rejection. The two groups were compared for the frequency and onset of the graft reaction. Results demonstrated no difference between control and experimental groups. The significance of these findings is discussed. | Concanavalin A |
The hemodynamic benefits and pulmonary vascular selectivity of amrinone, dobutamine and amrinone + dobutamine were assessed in a canine model of vasoconstrictive pulmonary hypertension. Dogs were equipped with central and peripheral catheters and with an electromagnetic flow probe placed around the ascending aorta for the measurement of cardiac function. Through a laparotomy, an arteriovenous fistula was created between the abdominal aorta and the inferior vena cava. Gradual opening of this fistula, which permitted construction of pressure-flow curves (mean pulmonary artery pressure over the cardiac index, PAP/CI), was utilized to identify the pulmonary vascular effects of amrinone and dobutamine. PGF2 alpha, prostaglandin derivative, induced stable pulmonary hypertension along with significant reduction in CI. The resultant pulmonary hypertension translated into a significant increase in both the slope and pressure intercept of the PAP/CI curve. The bipyridine derivative, amrinone, did not reverse the CI reduction observed with PGF2 alpha: both mean arterial pressure and PAP were decreased as was the intercept of the PAP/CI curve. Dobutamine, a beta-agonist, reversed the CI decline elicited by PGF2 alpha but the elevated pulmonary pressure remained unaffected; dobutamine reduced the slope of the PAP/CI curve. When combined, amrinone and dobutamine demonstrated additive beneficial hemodynamic effects and improved lung perfusion. Their additive effects were also indicated by data on the PAP/CI curve: both the slope and the pressure intercept were significantly reduced. These results suggest that amrinone and dobutamine interact at different sites of the pulmonary vasculature and that their association might be beneficial in vasoconstrictive pulmonary hypertension although no significant pulmonary vascular selectivity could be observed. | Amrinone |
Degradation of the retinal image by translucent occluders during postnatal development induces axial myopia in chickens, tree shrews and monkeys. Local visual deprivation produces myopia even in local regions of the eye and neither accommodation nor intact connection between the eye and the brain are necessary. Therefore, it is an important question whether a similar local-retinal pathway translating visual information into growth or stretch signals to the underlying sclera is acting to emmetropize the growing eye. It is not known until now whether occluder deprivation triggers similar eye growth (or scleral stretch) mechanisms that are also responsible for visual guidance of normal refractive development. We here report that, in chickens, 6-hydroxy dopamine suppresses deprivation-induced myopia but has no effect on the magnitude of changes in axial eye elongation that are induced by spectacle lenses. The result suggests that, in chickens with normal accommodation, two pharmacologically different feedback loops may be responsible for deprivation myopia and lens-induced refractive errors. | Oxidopamine |
The Mac Leod syndrome is a unilateral pulmonary hypoplasia with emphysema. Onset usually occurs in childhood. The authors delineate this well-defined nosologic entity which is one of the many etiologies of the unilateral hyperlucent lung. | Pulmonary Emphysema |
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