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BACKGROUND: The objective of this study was to evaluate the ex vivo removal of cytokines with an extracorporeal circuit using coupled large-pore haemofiltration and sorbent adsorption. METHODS: The setting for this study was a laboratory attached to the Intensive Care Unit of a tertiary hospital. Six healthy volunteers donated blood, which was incubated with endotoxin. Control blood was left at room temperature. Treatment blood was recirculated for 6 h through a closed circuit with a large-pore polysulfone haemofilter (average pore size 150 kDa) and an activated charcoal cartridge. Blood and ultrafiltrate were sampled hourly from three sites (pre-haemofilter for the circulating concentration, at cartridge inlet and cartridge outlet) to measure the concentrations of interleukins (IL)-1beta, -6, -8 and -10, and tumour necrosis factor (TNF). RESULTS: Control cytokine concentrations remained the same or increased slightly. Most of the preformed circuit cytokines were removed, with the exception of IL-10. The average sieving coefficients were 0.61 for IL-1beta, 1.34 for IL-6, 0.30 for IL-8, and 0.56 for TNF. Average single-pass clearances were 49, 107, 24 and 45 ml/min, respectively. The cartridge adsorbed 90% of IL-1beta, 72% of IL-6, 100% of IL-8, and 7% of TNF during each pass. CONCLUSION: The combination of a large-pore haemofilter and charcoal cartridge removed several cytokines efficiently under ex vivo conditions. This technique can now be tested for cytokine removal in vivo. | Inflammation Mediators |
Several classes of medications are available for the treatment of asthma, and often they must be taken concurrently to achieve asthma control. Based on the understanding of asthma as an inflammatory disease, the National Heart Lung and Blood Institute guidelines provide a stepwise approach to pharmacologic therapy. Corticosteroid therapy, principally inhaled corticosteroid (ICS) therapy, is considered the most effective anti-inflammatory treatment. In cases of moderate-to-severe persistent asthma, the addition of a second long-term control medication to ICS therapy is one recommended treatment option. A combination-product inhaler (Advair, Seretide) was developed to treat both the inflammatory and bronchoconstrictive components of asthma by delivering a dose of the ICS, fluticasone propionate, and a dose of the long-acting beta2-adrenergic (LABA) bronchodilator, salmeterol. The Advair Diskus is available in 3 strengths of fluticasone propionate (100, 250, and 500 microg) and a fixed dose (50 microg) of salmeterol. Combination treatment with both ICS and LABA provides greater asthma control than increasing the ICS dose alone, while at the same time reducing the frequency and perhaps the severity of exacerbations. Furthermore, salmeterol added to ICS therapy provides superior asthma control compared with the addition of leukotriene modifiers or theophylline. The superior control is likely a consequence of the complementary actions of the drugs when taken together, including the activation of the glucocorticoid receptor by salmeterol. By combining anti-inflammatory treatment with a long-acting beta2-agonist in a single inhaler (1 inhalation twice daily), physicians can provide coverage for both the inflammatory and bronchoconstrictive aspects of asthma without introducing any new or unexpected adverse consequences. The most common drug-related adverse events were those known to be attributable to the constituent medications (ICS therapy and/or LABA therapy). Although the benefits of combined ICS plus LABA therapy can be achieved with separate inhalers, the convenience of the combination product may improve patient adherence and may therefore reduce the morbidity of asthma." | Fluticasone-Salmeterol Drug Combination |
Malformations of cortical development encompass heterogeneous groups of structural brain anomalies associated with complex neurodevelopmental disorders and diverse genetic and nongenetic etiologies. Recent progress in understanding the genetic basis of brain malformations has been driven by extraordinary advances in DNA sequencing technologies. For example, somatic mosaic mutations that activate mammalian target of rapamycin signaling in cortical progenitor cells during development are now recognized as the cause of hemimegalencephaly and some types of focal cortical dysplasia. In addition, research on brain development has begun to reveal the cellular and molecular bases of cortical gyrification and axon pathway formation, providing better understanding of disorders involving these processes. New neuroimaging techniques with improved resolution have enhanced our ability to characterize subtle malformations, such as those associated with intellectual disability and autism. In this review, we broadly discuss cortical malformations and focus on several for which genetic etiologies have elucidated pathogenesis." | Malformations of Cortical Development, Group III |
Bronchopulmonary dysplasia or chronic lung disease of prematurity is a prolonged respiratory failure with multifactorial etiology in very low birth-weight neonates. This review summarizes current knowledge about the molecular mechanisms of different infections and inflammatory responses that are involved in the development of chronic lung disease of prematurity. | Infant, Premature, Diseases |
Pantoprazole is a proton pump inhibitor (PPI) that binds irreversibly and specifically to the proton pump, thereby reducing gastric acid secretion. Pantoprazole has a relatively long duration of action compared with other PPIs, and a lower propensity to become activated in slightly acidic body compartments. To date, no drug-drug interactions have been identified with pantoprazole in numerous interaction studies. Overall, in the short-term (8-10 weeks) initial treatment of gastro-oesophageal reflux disease (a condition that occurs when the reflux of gastric contents causes troublesome symptoms and/or complications) and long-term (6-24 months) maintenance therapy, oral pantoprazole 20 or 40 mg/day demonstrated similar efficacy to omeprazole, lansoprazole and esomeprazole and greater efficacy than histamine type 2 receptor antagonists. Pantoprazole is also effective in treating and preventing NSAID-related gastric and gastroduodenal injury. The optimal adult oral dose for gastric acid-related disorders is pantoprazole 40 mg once daily. Although data are limited, pantoprazole 20 or 40 mg/day was effective and well tolerated in the treatment of acid-related disorders in children and adolescents. Pantoprazole was also well tolerated in adults with acid-related disorders in short- and long-term studies. Thus, pantoprazole is a valuable agent for the management of acid-related disorders." | 2-Pyridinylmethylsulfinylbenzimidazoles |
While researchers have thoroughly studied the who, what, and when of first sexual experiences, we know much less about how people construct, experience, and proceed (or not) with sexual pleasure in these experiences and beyond. To address this knowledge gap, the Global Advisory Board for Sexual Health and Wellbeing (GAB) coordinated a rapid review of published peer-reviewed research to determine what is currently known about sexual pleasure in first sexual experiences. We found 23 papers exploring this subject and its intersections with sexual health and sexual rights. The results reveal significant gaps in erotic education, gender equity, vulnerability and connection, and communication efficacy; and highlight important domains to consider in future research. Our findings draw out the key features of pleasurable first sexual experience(s), namely that individuals with the agency to formulate their definition and context of what pleasure means to them are more likely to experience pleasure at first sex. This finding points to promising ways to improve first sexual experiences through erotic skills building and through addressing knowledge gaps about having sex for the first time among disadvantaged groups. | Pleasure |
This paper focuses on the vicissitudes of the supervisor/supervisee relationship and on the personal impact of supervision on the candidate. Conflicts within the supervisory situation and their potential intrusion into the learning process are discussed. The supervisee's character as a limiting factor and some of the dynamics of the parallel process are considered as well. A number of vignettes illustrate the problems involved and some possible remedies. | Displacement, Psychological |
For genome-wide CRISPR off-target cleavage sites (OTS) prediction, an important issue is data imbalance-the number of true OTS recognized by whole-genome off-target detection techniques is much smaller than that of all possible nucleotide mismatch loci, making the training of machine learning model very challenging. Therefore, computational models proposed for OTS prediction and scoring should be carefully designed and properly evaluated in order to avoid bias. In our study, two tools are taken as examples to further emphasize the data imbalance issue in CRISPR off-target prediction to achieve better sensitivity and specificity for optimized CRISPR gene editing. We would like to indicate that (1) the benchmark of CRISPR off-target prediction should be properly evaluated and not overestimated by considering data imbalance issue; (2) incorporation of efficient computational techniques (including ensemble learning and data synthesis techniques) can help to address the data imbalance issue and improve the performance of CRISPR off-target prediction. Taking together, we call for more efforts to address the data imbalance issue in CRISPR off-target prediction to facilitate clinical utility of CRISPR-based gene editing techniques. | Gene Editing |
Cerebral amyloid angiopathy (CAA) is a process of unknown etiology characterized by amyloid deposition in the wall of small cerebral and meningeal blood vessels. CAA is also a feature of Alzheimer's disease (AD) and of a subgroup of elderly people. Alpha-1-Antichymotrypsin (ACT) is a serum glycoprotein frequently associated with vascular and senile plaque amyloid. The ACT gene is known to have a bi-allele polymorphism that causes a simple amino acid substitution. In an attempt to clarify the possible role of ACT polymorphism in AD and in cases of CAA, the ACT genotype was investigated in AD, CAA, and intellectually intact controls. Representative brain areas (cerebral cortex, hippocampus, putamen, white matter, and gyrus cinguli) from all cases were studied using classical histologic staining techniques (hematoxylin-eosin (HE), Mallory's thrichromic or alkaline congo red stain), and immunohistochemistry for tau and beta-amyloid proteins. There was a significantly increased T allele and TT genotype frequency in the CAA group, but not in the AD group, suggesting a role for the ACT genotype in the development of vascular lesions. The presence of the apolipoprotein E4 allele (ApoE4) did not correlate with the ACT-A allele, as previously reported, and appeared to be independent of the risk for developing AD. | alpha 1-Antichymotrypsin |
OBJECTIVE: To compare preference judgments for sounds processed via a simulated five-channel compression hearing aid with gains and compression ratios selected according to two recently introduced fitting methods, CAMEQ2-HF (hereafter named CAM2) and NAL-NL2. DESIGN: There were 15 participants with sloping sensorineural hearing loss. They had mild losses, typical of people who might be candidates for wide-bandwidth hearing aids. Within a given trial, the same segment of sound was presented twice in succession to one ear, once with CAM2 settings and once with NAL-NL2 settings, in random order. The participant had to indicate which one was preferred and by how much. Judgments of overall sound quality were obtained for female and male speech in quiet and for four types of music (classical, jazz, a man singing, and percussion). Judgments of speech clarity were obtained for female and male speech in speech-shaped noise, female speech in a male-talker background, and male speech in a female-talker background. Factors investigated included compression speed (slow or fast) and input sound level (50, 65, or 80 dB SPL). RESULTS: The pattern of the results was reasonably consistent across participants, but the magnitude of the effects was small. For judgments of overall sound quality, nine participants preferred CAM2 relative to NAL-NL2, and the remainder showed no clear preference. There was a significant overall preference for CAM2. The preference for CAM2 over NAL-NL2 in overall sound quality was present for all types of stimuli, both compression speeds, and all three levels. For judgments of the clarity of speech in noise, five participants preferred CAM2 over NAL-NL2, one showed the opposite preference, and the remainder showed no clear preference. There was a significant overall preference for CAM2. The preference for CAM2 over NAL-NL2 in the context of clarity of speech in noise was present for all types of stimuli, both compression speeds, and all three levels. For judgments of the clarity of speech in a background talker, CAM2 was significantly preferred overall relative to NAL-NL2, but the effect was very small. CONCLUSIONS: For participants with mild sloping hearing loss, a simulated hearing aid unilaterally fitted using CAM2 was preferred over the same aid fitted using NAL-NL2 for overall sound quality and the clarity of speech in noise. Preferences differed only very slightly for the clarity of speech in a background talker. Further work is needed to establish whether similar preferences would be found in everyday life." | Correction of Hearing Impairment |
Sexual dysfunctions in women are classified into disorders of desire, arousal, orgasm, and pain (including dyspareunia and vaginismus). As the cognitive behavioral treatment (CBT) procedures differ among these sexual disorders, the treatments for each disorder are reviewed separately. The efficacy of CBT differs depending on the specific sexual dysfunction to be treated. It is concluded that only a few CBT treatments for women's sexual dysfunction have yet been empirically investigated in a methodologically sound way and little is known about which of the treatment components are most effective." | Sexual Dysfunctions, Psychological |
The phosphorylating reagent bis[S-(4,4'-dimethoxytrityl)-2-mercaptoethyl]-N,N-diisopropylphosphoramidite is prepared in three steps from commercial methyl thioglycolate and diisopropylphosphoramidous dichloride. The phosphorylating reagent has been used successfully in the solid-phase synthesis of deoxyribonucleoside 5'-/3'-phosphate or -thiophosphate monoesters and oligonucleotide 5'-phosphate/-thiophosphate monoesters. Bis[S-(4,4'-dimethoxytrityl)-2-mercaptoethyl]-N,N-diisopropylphosphoramidite has also been employed in the construction of a thermolytic dinucleotide prodrug model to evaluate the ability of the reagent to produce thermosentive oligonucleotide prodrugs under mild temperature conditions ( approximately 25 degrees C) for potential therapeutic applications. | Deoxyribonucleosides |
One of the main advantages of measures of automatic cognition is supposed to be that they are less susceptible to faking than explicit tests. It is an empirical question, however, to what degree these measures can be faked, and the response might well differ for different measures. We tested whether the Implicit Association Test (IAT, Greenwald, McGhee, & Schwartz, 1998) cannot be faked as easily as explicit measures of the same constructs. We chose the Big-Five dimensions conscientiousness and extraversion as the constructs of interest. The results show, indeed, that the IAT is much less susceptible to faking than questionnaire measures are, even if no selective faking of single dimensions of the questionnaire occurred. However, given limited experience, scores on the IAT, too, are susceptible to faking. | Word Association Tests |
The archaeal protein L7Ae forms part of a protein complex in the ribosome that specifically recognizes and binds to kink-turn RNA. In this complex, L7Ae directly interacts with the oligonucleotide and creates a functional arrangement for site-specific 2'-O-methylation. We report the solution NMR backbone assignment of Methanocaldococcus jannaschii L7Ae (117 residues, 12.7 kDa) in the ligand-free state and when bound to a 25 nucleotide C/D box kink-turn mimic RNA. | Methanocaldococcus |
The National Institute of Mental Health recently launched the Research Domain Criteria (RDoC). The RDoC is an initiative to improve classification of mental health concerns by promoting research on the brain mechanisms underlying these concerns, with the ultimate goal of developing interventions that target these brain mechanisms. A key focus of RDoC involves opening new lines of research examining patients' responses on biological measures. The RDoC presents unique challenges to mental health professionals who work with children and adolescents. Indeed, mental health professionals rarely integrate biological measures into clinical assessments. Thus, RDoC's ability to improve patient care rests, in part, on the development of strategies for implementing biological measures within mental health assessments. Further, mental health professionals already carry out comprehensive assessments that frequently yield inconsistent findings. These inconsistencies have historically posed challenges to interpreting research findings as well as assessment outcomes in practice settings. In this introductory article, we review key issues that informed the development of a special issue of articles demonstrating methods for implementing low-cost measures of physiological functioning in clinical child and adolescent assessments. We also outline a conceptual framework, informed by theoretical work on using and interpreting multiple informants' clinical reports (De Los Reyes, Thomas, Goodman, & Kundey, 2013 ), to guide hypothesis testing when using physiological measures within clinical child and adolescent assessments. This special issue and the conceptual model described in this article may open up new lines of research testing paradigms for implementing clinically feasible physiological measures in clinical child and adolescent assessments." | National Institute of Mental Health (U.S.) |
With the development of human society, there is an increasing importance for reliable person identification and authentication to protect a person's material and intellectual property. Person identification based on brain signals has captured substantial attention in recent years. These signals are characterized by original patterns for a specific person and are capable of providing security and privacy of an individual in biometric identification. This study presents a biometric identification method based on a novel paradigm with accrual cognitive brain load from relaxing with eyes closed to the end of a serious game, which includes three levels with increasing difficulty. The used database contains EEG data from 21 different subjects. Specific patterns of EEG signals are recognized in the time domain and classified using a 1D Convolutional Neural Network proposed in the MATLAB environment. The ability of person identification based on individual tasks corresponding to a given degree of load and their fusion are examined by 5-fold cross-validation. Final accuracies of more than 99% and 98% were achieved for individual tasks and task fusion, respectively. The reduction of EEG channels is also investigated. The results imply that this approach is suitable to real applications. | Biometric Identification |
AIM: Compounds containing Bupleurum possess immunomodulating effects. KY88 LIVER LIVO (KY88) is a blend of such compound. The aim of this study is to investigate the effects of KY88 on the production of cytokines by lymphocytes in vitro. METHODS: Seventy Sprague Dawley rats were used of which 40 were orally fed with 4 mg purified KY88 for 35 d. Normal human lymphocytes were isolated and cultured in standard conditions. The culture medium was collected at zero and 72 h after the KY88 treatment. The cytokines, including interleukin-1beta (IL-1beta), IL-2, IL-4, IL-6, tumor necrosis factor-alpha (TNF-alpha), and interferon-gamma, were measured by ELISA kits. RESULTS: TNF-alpha levels in the supernatant of cultured human lymphocytes significantly increased after the treatment of PHA and KY88. The mean levels were (855+/-251), (399+/-145), and (176+/-49) ng/L after the treatment with KY88 at the concentrations of 10, 1 and 0.1 g/mL respectively. However, the level in the control group without specific treatment was only (68+/-4) ng/L. The difference between KY88 10 g/mL and control groups was significant (P<0.05). All other cytokines did not show significant variations between KY88 and the control groups. KY88 may regulate the immune function through the induction of TNF-alpha expression. | Bupleurum |
Plasmablastic lymphoma is a non-Hodgkin lymphoma characterized by its plasmacytic differentiation and predilection for the oral cavity. It is among the lymphomas most commonly associated with AIDS. This report details a case of a HIV-positive patient with a 1-month history of an exophytic mass in the gingival area of the upper left quadrant. The diagnosis of plasmablastic lymphoma was made based on its histopathological and immunophenotypical features. She was treated with chemotherapy followed by autologous hematopoietic stem cell transplantation. Despite complete resolution of the lesion, the patient died of cardiorespiratory arrest. This case illustrates plasmablastic lymphoma as the first clinical manifestation of AIDS, highlighting the importance of differentiating between a potentially malignant lesion and other pathologic processes. | Plasmablastic Lymphoma |
Electronic cigarette use is particularly prevalent in adolescents, but the effects of secondhand exposure to nicotine vapor in adolescents on the propensity to develop nicotine dependence and increase nicotine self-administration in adulthood are poorly known. The present study explored the effects of nicotine vapor exposure on withdrawal-like states (hyperalgesia, spontaneous withdrawal signs, and locomotor activity) in adolescent rats and the vulnerability to acquire intravenous nicotine self-administration in adulthood. Adolescent (postnatal day 38) rats were exposed to intermittent nicotine vapor (14â¯h/day) for 7 consecutive days in a range of doses (0, 0.4, and 7â¯mg/m(3)). The rats were tested for somatic, emotional, and motivational withdrawal symptoms. When the animals reached adulthood, they were allowed to self-administer nicotine (0.03â¯mg/kg/0.1â¯ml) intravenously in operant chambers for 1â¯h/day for 12 consecutive days. Rats that were exposed to nicotine vapor presented moderate to severe signs of spontaneous withdrawal after the cessation of nicotine vapor. No effect on anxiety-like behavior was observed. Rats that were exposed to high levels of nicotine vapor in adolescence had lower pain thresholds and exhibited faster and higher acquisition of nicotine self-administration in adulthood. Chronic exposure to nicotine vapor in adolescent rats produced a withdrawal-like state and facilitated the acquisition of intravenous nicotine self-administration in adulthood. These results suggest that exposure of adolescents to nicotine vapor may confer higher risk of developing nicotine dependence when they become adults. | Nicotine |
Human gnathostomiasis is most frequently caused by the nematode Gnathostoma spinigerum. This disease is endemic to Southeast Asia, particularly Thailand and Japan. The clinical presentation is most commonly characterized by localized, intermittent, migratory swellings of the skin and subcutaneous tissues, often in association with localized pain, pruritus, and erythema. Since this worm can migrate to deeper tissues, any organ system may become involved. Characteristically, patients with gnathostomiasis have a moderate to severe elevation of the peripheral eosinophil count, with values not uncommonly exceeding 50% of the total white blood cell count. With modern-day travel and immigration, cases of gnathostomiasis are being diagnosed with increased frequency in the United States. Because of its rarity in this country, however, gnathostomiasis often is not included in an initial differential diagnosis despite the characteristic triad of intermittent migratory swelling, a history of travel to Southeast Asia, and eosinophilia. We report a case of cutaneous gnathostomiasis diagnosed in the United States, and we present a clinical review of the English-language literature on human gnathostomiasis. | Spirurina |
A portable peak flow meter based on a turbine transducer that can display results in code has been developed. Its performance compares well with the Wright peak flow meter. Records of subjective self assessment of asthma on a visual analogue scale and of peak flow (PEF) were compared in 12 subjects with asthma. PEF measurements were made with a coded meter for two weeks and an uncoded meter for two weeks in random order. The correlation between visual analogue scale score and PEF was invariably stronger when PEF was known. Changes in perception of asthma were measured by comparing the slopes and relative positions of the regressions of visual analogue on PEF. When PEF was uncoded awareness of asthma was significantly increased in five patients, predominantly those whose perception was poorest while they were using the coded meter, and decreased in only one patient. In two patients the results were unsuitable for this type of analysis. Knowledge of PEF therefore may influence subjective self assessment in patients with bronchial asthma. For objective studies of symptoms of asthma, PEF readings should be unknown to the patient. Perception of asthma may, however, be improved in patients with poor ability to detect changes in bronchial calibre by uncoded measurement of peak flow at home. | Peak Expiratory Flow Rate |
Rickettsialpox is a rare mite-borne rickettsiosis that is encountered in urban populations in the eastern United States and throughout the world. It is characterized clinically by an eschar, fever, and a papulovesicular eruption. Both of these cutaneous manifestations may be mimicked by infectious diseases that have been designated as bioterrorist agents by the United States Centers for Diseases Control and Prevention: the former by anthrax, and the latter by smallpox. It is thus important for clinicians to be familiar with rickettsialpox. We report 3 cases and review the epidemiology, clinical and laboratory findings, differential diagnosis, and management of this disease. | Rickettsiaceae Infections |
This paper provides an overview of ethical issues in obstetrics and gynecology. We first define two basic ethical principles, beneficence and respect for autonomy. We first apply these principles to gynecologic practice, emphasizing the role of informed consent. We then apply these principles to obstetric practice, utilizing the concept of the fetus as a patient and identifying its clinical implications for directive versus non-directive counseling for fetal benefit. | Principle-Based Ethics |
Eliminating industrially produced trans-fatty acids (TFAs) from the food supply is one of the World Health Organization's (WHO's) priority targets to control and prevent non-communicable diseases. This review paper describes the strategies used to reduce TFA consumption in Thailand based on a situation analysis consisting of an assessment of TFA content in the national food supply, its intake, and stakeholder-based analysis of Strengths, Weaknesses, Opportunities, and Threats (SWOT). The analysis resulted in the drafting of a regulatory approach, which was then considered by stakeholders. Bakery products containing partially hydrogenated oils (PHOs) are the major sources of TFAs in Thailand. Palm and coconut oil as well as blending technology are locally available as PHO replacements. Thailand's Food and Drug Administration has taken legal action to prohibit the production, import, and distribution of PHOs and their products. Post-marketing TFA levels are currently being monitored, ie, TFAs in fat/oil and butter must not exceed 2% and 6% of fat content, respectively. For other food categories, TFAs must not exceed 0.5 g per serving unless the TFAs are from ruminant sources. The key factor to successfully reducing TFAs in Thailand is the partnership between public and private sectors, professional associations, and consumers, based on scientific evidence regarding the negative impact of TFA intake on cardiovascular health. | Trans Fatty Acids |
This paper reports for the first time the morphology of larval stages of Setaria labiato-papillosa. The infective larvae of this species had two circles of small papillae on the cephalic end, 4 papillae for outer circle and 6 for inner circle. The caudal end of S. labiato-papillosa is in digital form with 3 transversally arranged papillae. There are 2 circles of small papillae on the cephalic end of S. leichungwingi and S. equina, 4 for each circle; the caudal terminal of the former species is willow-shaped with 3 pearl-like papillae, and that of the latter is conical shaped with 1 bulbed papilla, 2 slightly protruded papillae at sub-terminal. The anal ratios of all the above 3 species are below 3. Morphology of larval stages of Dirofilaria repens was also primarily described in China. The 3 bulbed caudal papillae of the infective larvae are closely arranged, and the anal ratio being less than 2. A key to infective larvae of 8 species of filaria was worked out according to relevant literature and the present study. | Setariasis |
Rhodococcus equi causes pulmonary and extrapulmonary infections in animals and humans, with endemic situations and significant young foal mortality in stud farms worldwide. Despite its economic impact in the horse-breeding industry, the broad geographic and host distribution, global diversity and population structure of R. equi remain poorly characterised. In this context, we developed a multilocus sequence typing (MLST) scheme using 89 clinical and environmental R. equi of various origins and eight Rhodococcus sp. Data can be accessed at http://pubmlst.org/rhodococcus/. A clonal R. equi population was observed with 16 out of 37 sequence types (STs) grouped into six clonal complexes (CC) based on single-locus variants. One of the six CCs (CC3) is not host-specific, suggesting potential exchanges between different R. equi reservoirs. Most of the virulent equine R. equi CCs/unlinked STs were plasmid-type-specific. Despite this, marked genetic variability with the circulation of multiple R. equi genotypes was generally observed even within the same animal. Focusing on outbreaks, data indicated (i) the potential contagious transmission of R. equi during the 2012-Mayotte equine outbreak because of the poor genotype diversity of clinical strains; (ii) a potential porcine outbreak among the 30 Belgian farms investigated in 2013. This first Rhodococcus equi MLST is a powerful tool for further epidemiological investigations and population biology studies of R. equi isolates. | Multilocus Sequence Typing |
Two generic radiosynthetic routes for the preparation of [11C-carbonyl]isocyanates have been developed. Reaction of N-organo-sulfinylamines; RNSO, (R = Me, Et, allyl, cyclohexyl and phenyl) with [11C]phosgene gave the corresponding [11C-carbonyl]isocyanates in good radiochemical yield (53-68%) from [11C]phosgene (decay corrected) in ca 16 min from EOB. Alternatively, the reaction of [11C]phosgene with N,N'-organo-ureas; (RNH)(2)CO, (R = Me, Et, Pr and phenyl) also gave the corresponding [11C-carbonyl]isocyanates in moderate radiochemical yield (9-37%) from [11C]phosgene (decay corrected) in ca 16 min from EOB. For identification, the [11C-carbonyl]organo-isocyanates were derivatized with 1-(2-methoxyphenyl)piperazine in situ to [11C-carbonyl]carboxamides and the position of radiolabelling in the carbonyl group confirmed by [11/13C]co-labeling and subsequent carbon-13 NMR spectroscopy. | Isocyanates |
The study examined the potentiation of the antinociceptive action of opioid analgesics produced by gaseous superoxide (GS) in the rat hind paw withdrawal test (PWT) and by GS or hydrogen peroxide (HP) in the formalin test. In the PWT, inhalation of GS for 50 minutes before i.p. injection of threshold doses of morphine (0.5 mg/kg) and trimeperidine (1.0 mg/kg) increased the threshold of nociception (TN) by a maximum of 43.0% (p < 0.05) and 113.4% (p < 0.01) respectively. The GS/trimeperidine-dependent increase in TN showed two peaks, the second of which could be suppressed by nialamide. Naloxone abolished the GS/ morphine-dependent increased in the TN. In the formalin test, a significant antinociceptive effect developed after GS inhalation or HP administration (intranasally, 2 x 5 microliters of 2 x 10(-5) mol/l solution in saline) in combination with low doses of Omnopon (0.06-0.75 mg/kg). These results suggest that both GS and HP potentiate the antinociceptive effects of opioid analgesics. | Nialamide |
The use of formaldehyde in dentistry has been discussed for years. This because of the possible systemic effects of its use. This paper addresses the possible systemic effects of the use of formaldehyde and the question in which dental products formaldehyde is a component. The indications for the use of formaldehyde as its alternatives are listed. The conclusion is that for nearly all dental indications for the use of formaldehyde good alternatives are available. | Dental Disinfectants |
Citrus peel juice and molasses are extremely bitter and unpalatable byproducts of orange and grapefruit juice production. Major components of interest are soluble sugars, glucose, fructose, and sucrose, which account for 60-70% of the dry solids. Analyses indicate that the remaining components are suspended tissue fragments, proteins, organic acids, mineral ions, phenolic compounds, and polyols. A purification sequence that removed a majority of bitter limonoids and phenolic compounds by adsorption on nonionic, macroporous resins was tested. Residual phenolic compounds were removed by adsorption on activated carbon or anion-exchange resin, which also removed anions of organic and inorganic acids. Taste panel results suggested that debittered products could be acceptable for food uses. | Molasses |
OBJECTIVE: To report a case of pulmonary edema associated with the use of ocular metipranolol, a nonselective beta-blocker. CASE SUMMARY: A 72-year-old woman with no history of pulmonary or cardiac disease presented to the emergency room with signs and symptoms consistent with cardiogenic pulmonary edema. The patient had used metipranolol eyedrops approximately 1 hour before becoming symptomatic. When rechallenged inadvertently while hospitalized, the patient again became symptomatic. The patient's metipranolol eyedrops then were substituted with betaxolol eyedrops. She continued to be free of symptoms of pulmonary edema at subsequent clinic visits 1, 4, and 6 weeks following discharge. DISCUSSION: This is the first reported case of pulmonary edema associated with metipranolol. There was a reasonable temporal association between use of the eyedrops and the onset of symptoms. Beta-blockers may cause cardiogenic pulmonary edema secondary to their negative inotropic and negative chronotropic effects. The drug's lipid solubility or a deficiency in the enzyme responsible for its metabolism may have allowed the drug to accumulate to a critical concentration over the 6-week period of use. CONCLUSIONS: Ocular beta-blockers must be used with caution in patients with relative contraindications to beta-blockade. This case illustrates that these agents must be used prudently even in patients with no history of symptomatic congestive heart failure. | Metipranolol |
Penile trauma, though rare, requires specialized management. Fibrotic sequelae from lesions of the tunica albuginea and corpora cavernosa must be prevented given their impact of the erectile function. Knowledge of penile anatomy enables acquisition and interpretation of penile MRI, preferably performed in the first few hours following injury. Tear of the tunica albuginea must be identified since it requires surgical management. Other lesions may be present at the acute (hematoma) or chronic (fibrosis, arteriocavernous fistula) phases. MRI, non-invasive and painless, is the imaging modality of choice in the multiplanar evaluation of traumatic injuries of the penis. | Penis |
OBJECTIVES: Cloninger developed the three-dimensional personality theory and Tridimensional Personality Questionnaire (TPQ), which shows that some dimensions of personality traits are heritable and related to neurotransmitters including dopamine. glutathione peroxidase 1 (GPx1) plays an important role in metabolic dopamine change and closely relates to neurological and psychiatric disorders. The impact of GPx-1 polymorphisms has been rarely explored in the field of personality traits. We decide to explore the relationships between them in healthy Chinese-Han subjects by using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). METHODS: In our study, 493 healthy Chinese-Han participants (male = 234, female = 259) were recruited. 2 ml of EDTA-treated blood from each volunteer was taken; meanwhile, personality traits were assessed by TPQ. We detected the genotypes of selected two polymorphisms through PCR-RFLP after extracting DNA. Finally, the association between different genotypes and TPQ scores was performed using SPSS, p < .05 is seen as significant statistical significance. RESULTS: Our data found a correlation between rs1800668 and novelty seeking (NS) subscale NS2 (X(2) = 7.392, p = .025). While the results showed the rs1050450 was significantly associated with NS4 (X(2) = 6.059, p = .048). Regarding sex stratification, there was a significant difference in the NS2 score (X(2) = 8.232, p = .016) among women for rs1800668. No sex effect was observed for either genotype for rs1050450. CONCLUSION: GPx-1polymorphism is related to personality traits in healthy Chinese-Han subjects. Our results suggested that GPx-1 may be involved in the biological mechanisms and be a potential gene that influenced personality. | Glutathione Peroxidase GPX1 |
Sandhoff disease is an infrequent, genetically caused disorder with a recessive autosomal inheritance pattern. It belongs to the gangliosidosis GM2 group and is produced by mutations in gen HEXB leading to reduction in enzymatic activity of enzymes beta-hexosaminidase A and B. Adult-onset GM2 gangliosidosis is rare. Here we report a white male who presented at age 69 with a fast-progression, motor neuron disease, mimicking amyotrophic lateral sclerosis (ALS), combined with autonomic dysfunction, sensory ataxia, and exaggerated startle to noise. Enzymatic assays demonstrated deficiency of both Hexosaminidases A and B leading to the diagnosis of Sandhoff disease. | Gangliosidoses, GM2 |
Three complementation groups of a pet mutant collection have been found to be composed of respiratory-deficient deficient mutants with lesions in mitochondrial protein synthesis. Recombinant plasmids capable of restoring respiration were cloned by transformation of representatives of each complementation group with a yeast genomic library. The plasmids were used to characterize the complementing genes and to institute disruption of the chromosomal copies of each gene in respiratory-proficient yeast. The sequences of the cloned genes indicate that they code for isoleucyl-, arginyl- and glutamyl-tRNA synthetases. The properties of the mutants used to obtain the genes and of strains with the disrupted genes indicate that all three aminoacyl-tRNA synthetases function exclusively in mitochondrial proteins synthesis. The ISM1 gene for mitochondrial isoleucyl-tRNA synthetase has been localized to chromosome XVI next to UME5. The MSR1 gene for the arginyl-tRNA synthetase was previously located on yeast chromosome VIII. The third gene MSE1 for the mitochondrial glutamyl-tRNA synthetase has not been localized. The identification of three new genes coding for mitochondrial-specific aminoacyl-tRNA synthetases indicates that in Saccharomyces cerevisiae at least 11 members of this protein family are encoded by genes distinct from those coding for the homologous cytoplasmic enzymes. | Arginine-tRNA Ligase |
The cholecystographic radiopaque agents, adipiodon and endographin, unlike the urographic contrast agents, triombrin and iodamide, decrease the fluorescence intensity of hydrophobic probes 1-anilinonaphthalene-8-sulfonate and 4-dimethylaminochalcone in plasmic membranes (PM) of rat hepatocytes primarily at the expense of the lowering of the constant of probe association with the membranes. The similar but less marked effects were discovered in experiments with lecithin lyposomal preparations. As regards the intensity of action, cardiotrast and triotrast an intermediate position between the two groups of radiographic contrast agents. Adipiodon and endographin induce an inhibition of membranous Mg+2 (Na+, K+) ATPase, which correlates with their effect on the structure of the hepatocyte PM. The data obtained allow a conclusion that, unlike the urographic agents, the cholecystographic radiopaque agents are bound to the definite areas of the hepatocytic PM and provoke alterations in the activity of membranous APTase because of the conformational rearrangements of the membranes. | Iodopyracet |
OBJECTIVES: To assess through literature case analysis how advances in lymphatic imaging, interventional radiology, and lymphatic vascular microsurgery illuminate and improve the lymphatic-flow status in select patients with Noonan syndrome (NS) who have undergone surgical intervention as a part of their comprehensive and individualized treatment plan. Also, we sought to illustrate the spectrum of lymphatic complications that can occur in this patient population when lymphatic flow through abnormal vasculature is surgically disrupted. METHODS: A literature review was performed by searching Noonan AND Lymphatic AND Imaging" in the PubMed database. Inclusion criteria for this study were (1) diagnosis and clinical description of at least one original patient with NS, (2) imaging figures depicting lymphatic structure and function or a description of lymphatic imaging findings when a figure is not present, and (3) documentation of either lymphatic surgical intervention or lymphatic complications resulting from other procedures. Patient cases were first grouped by documented surgical intervention type, then clinical outcomes and lymphatic imaging results were compared. RESULTS: A total of 18 patient cases from 10 eligible publications were included in our review. Lymphatic imaging findings across all patients included lymphatic vessel dysplasia along with flow disruption (n = 16), thoracic duct malformations (n = 12), dermal lymphatic reflux (n = 7), and dilated lymphatic vessels (n = 4). Lymphovenous anastomosis (n = 4) resulted in rapid improvement of patient symptoms and signs. New-onset lymphatic manifestations noted over 10 to 20 years for two of these patients were chylothorax (n = 1), erysipelas (n = 1), and gradual-onset nonchylous scrotal lymphorrhea (n = 1). Targeted endovascular lymphatic disruption via sclerosis, embolization, or ablation (n = 8) results were mixed depending on the degree of central lymphatic involvement and included resolution of symptoms (n = 1), postoperative abdominal hemorrhage (n = 1), stable condition or minor improvement (n = 5), and death (n = 2). Large lymphatic vessel ligation or accidental incision (n = 6) occurred during thoracotomy (n = 4), scrotoplasty (n = 1), or inguinal lymph node biopsy (n = 1). These resulted in postoperative onset of new-onset regional lymphatic reflux (n = 5), chylothorax (n = 4), death (n = 3), or persistent or unchanged symptoms (n = 1). CONCLUSIONS: Imaging of the central lymphatics enabled characterization of lymphatic developmental features and guided operative management of lymphatic vascular defects in patients with NS. This review of the literature suggests that the surgical preservation or enhancement of central lymphatic return in patients with NS may improve interventional outcomes, whereas the disruption of central lymph flow has significant potential to cause severe postoperative complications and worsening of the patient's clinical condition." | Lymphatic Vessels |
A thermal extraction-two-dimensional gas chromatography-mass spectrometry (TE-GC-GC-MS) method with heart-cutting is developed for quantitatively assessing nitrogen (N)-bearing organic species (e.g., pyrrole, pyridine, nitriles, and amines) in aerosols emitted from agricultural fires. Pyrolysis of the constituents in the crop residue is a likely formation pathway for these compounds. An evaluation of the TE-GC-GC-MS method proficiency for them confirms low carryover (<1%), adequate recovery (84-100%), high reproducibility (<9% RSD), picogram method detection limits, and a linear dynamic range spanning four orders of magnitude. The 14 substances for which quantitative results are available are primarily heterocyclic aromatic N compounds that comprise 0.7% (w/w) of the total fine aerosol mass. The benefits of TE-GC-GC-MS versus conventional GC-MS methods for organic N species in aerosols may depend on the matrix and the target N analyte concentration in that matrix; for the biomass burning aerosol examined in this study, the former approach reduces the unresolved complex mixture and detects organic N species not seen with GC-MS. We show another advantage of TE-GC-GC-MS is that it adequately resolves the anhydro-sugar (e.g., levoglucosan), alkanoic acid, and substituted phenol molecules in the biomass burning aerosol without the use of methylation or trimethyl-silyl derivatizing agents. | Aerosols |
High-pressure x-ray emission measurements are used to provide crucial evidence in the longstanding debate over the nature of the isostructural (alpha, gamma) volume collapse in elemental cerium. Extended local atomic model calculations show that the satellite of the Lgamma emission line offers direct access to the total angular momentum observable (J(2)). This satellite experiences a 30% steplike decrease across the volume collapse, validating the Kondo model in conjunction with previous measurements. Direct comparisons are made with previous predictions by dynamical mean field theory. A general experimental methodology is demonstrated for analogous work on a wide range of strongly correlated f-electron systems. | Spectrometry, X-Ray Emission |
The human leukocyte antigen system (HLA) is a cluster of highly polymorphic genes essential for the proper function of the immune system, and it has been associated with a wide range of diseases. HLA class I molecules present intracellular host- and pathogen-derived peptides to effector cells of the immune system, inducing immune tolerance in healthy conditions or triggering effective immune responses in pathological situations. HLA-C is the most recently evolved HLA class I molecule, only present in humans and great apes. Differentiating from its older siblings, HLA-A and HLA-B, HLA-C exhibits distinctive features in its expression and interaction partners. HLA-C serves as a natural ligand for multiple members of the killer-cell immunoglobulin-like receptor (KIR) family, which are predominately expressed by natural killer (NK) cells. NK cells are crucial for the early control of viral infections and accumulating evidence indicates that interactions between HLA-C and its respective KIR receptors determine the outcome and progression of viral infections. In this review, we focus on the unique role of HLA-C in regulating NK cell functions and its consequences in the setting of viral infections. | HLA-C Antigens |
Body composition during puberty is a marker of metabolic changes that occur during this period of growth and maturation, and, thus, holds key information regarding current and future health. During puberty, the main components of body composition (total body fat, lean body mass, bone mineral content) all increase, but considerable sexual dimorphism exists. Methods for measuring body composition (e.g. densitometry and dual-energy X-ray absorptiometry) and degree of maturity will be discussed in this review. Components of body composition show age-to-age correlations (i.e. 'tracking'), especially from adolescence onwards. Furthermore, adipose tissue is endocrinologically active and is centrally involved in the interaction between adipocytokines, insulin and sex-steroid hormones, and thus influences cardiovascular and metabolic disease processes. In conclusion, pubertal body composition is important, not only for the assessment of contemporaneous nutritional status, but also for being linked directly to the possible onset of chronic disease later in life and is, therefore, useful for disease risk assessment and intervention early in life. | Body Composition |
Cell invasion into the surrounding extracellular matrix or across tissue boundaries and endothelial barriers occurs in both physiological and pathological scenarios such as immune surveillance or cancer metastasis. Podosomes and invadopodia, collectively called 'invadosomes', are actin-based structures that drive the proteolytic invasion of cells, by forming highly regulated platforms for the localized release of lytic enzymes that degrade the matrix. Recent advances in high-resolution microscopy techniques, in vivo imaging and high-throughput analyses have led to considerable progress in understanding mechanisms of invadosomes, revealing the intricate inner architecture of these structures, as well as their growing repertoire of functions that extends well beyond matrix degradation. In this Review, we discuss the known functions, architecture and regulatory mechanisms of podosomes and invadopodia. In particular, we describe the molecular mechanisms of localized actin turnover and microtubule-based cargo delivery, with a special focus on matrix-lytic enzymes that enable proteolytic invasion. Finally, we point out topics that should become important in the invadosome field in the future. | Podosomes |
Obstructive azoospermia accounts for 40% of azoospermia and results from obstruction of the excurrent ducts (due to many causes) at any location between the rete testis and the ejaculatory ducts. The diagnosis of obstructive azoospermia (OA) requires a stepwise approach to differentiate it from nonobstructive OA and to formulate management options. Localization of the site of obstruction relies on history, physical examination, and possibly laboratory, genetic, imaging tests, and intraoperative findings. The prospects for patients with OA are excellent given recent advances in microsurgical approaches and in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI). Successful outcomes are increasingly likely after microsurgical reconstruction techniques, permitting non-IVF pregnancies for many couples. When reconstruction is not an option, microsurgical sperm retrieval provides excellent outcomes for patients in conjunction with IVF and ICSI. | Azoospermia |
Four triterpene saponins, agrostemmosides A-D were isolated from the methanol extract of Agrostemma gracilis. The structures of the compounds were determined as 3-O-beta-D-xylopyranosyloleanolic acid 28-O-beta-D-glucopyranosyl-(1-->2)-[beta-D-xylopyranosyl-(1-->6)]-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranosyl ester, 3-O-alpha-L-rhamnopyranosyl-(1-->2)-beta-D-xylopyranosyloleanolic acid 28-O-beta-D-glucopyranosyl-(1-->2)-[beta-D-xylopyranosyl-(1-->6)]-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranosyl ester, 3-O-beta-D-xylopyranosylechinocystic acid 28-O-beta-D-glucopyranosyl-(1-->2)-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranosyl ester, 3-O-beta-D-xylopyranosylechinocystic acid 28-O-beta-D-glucopyranosyl-(1-->2)-[beta-D-xylopyranosyl-(1-->6)]-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranosyl ester by a combination of one- and two-dimensional NMR techniques, and mass spectrometry. To the best of our knowledge this is the first phytochemical report on A. gracilis, and echinocystic acid saponins were encountered for the first time in Caryophyllaceae family. | Agrostemma |
In a comparative study of erythrocyte metabolism of vertebrates, the specific activity of glucose-6-phosphate dehydrogenase (G6PD) of the Brazilian opossum Didelphis marsupialis in a hemolysate was shown to be high, 207 +/- 38 IU g-1 Hb-1 min-1 at 37 degrees C, compared to the human erythrocyte activity of 12 +/- 2 IU g-1 Hb-1 min-1 at 37 degrees C. The apparent high specific activity of the mixture led us to investigate the physicochemical properties of the opossum enzyme. We report that reduced glutathione (GSH) in the erythrocytes was only 50% higher than in human erythrocytes, a value lower than expected from the high G6PD activity since GSH is maintained in a reduced state by G6PD activity. The molecular mass, determined by G-200 Sephadex column chromatography at pH 8.0, was 265 kDa, which is essentially the same as that of human G6PD (260 kDa). The Michaelis-Menten constants (Km: 55 microM) for glucose-6-phosphate and nicotinamide adenine dinucleotide phosphate (Km: 3.3 microM) were similar to those of the human enzyme (Km: 50-70 and Km: 2.9-4.4, respectively). A 450-fold purification of the opossum enzyme was achieved and the specific activity of the purified enzyme, 90 IU/mg protein, was actually lower than the 150 IU/mg protein observed for human G6PD. We conclude that G6PD after purification from the hemolysate of D. marsupialis does not have a high specific activity. Thus, it is quite probable that the red cell hyperactivity reported may be explained by increased synthesis of G6PD molecules per unit of hemoglobin or to reduced inactivation in the RBC hemolysate." | Glucosephosphate Dehydrogenase |
Systemic juvenile idiopathic arthritis is a distinct and heterogeneous disease presently classified under the umbrella of juvenile idiopathic arthritis, with some patients following a monophasic remitting course, whereas others have persistent disease with chronic organ- and life-threatening complications. Although biologic therapies have revolutionized treatment, recent follow-up studies report significant numbers of children with persistently active disease on long term follow-up. This review focuses on refractory disease courses, specifically refractory arthritis, systemic juvenile idiopathic arthritis with recurrent, or longstanding signs of macrophage activation syndrome, and systemic juvenile idiopathic arthritis associated with suspected, probable, or definite lung disease." | Macrophage Activation Syndrome |
Escherichia coli seryl-tRNA synthetase (SerRS) a dimeric class II aminoacyl-tRNA synthetase with two structural domains charges specifically the five iso-acceptor tRNA(ser) as well as the tRNA(sec) (selC product) of E. coli. The N-terminal domain is a 60 A long arm-like coiled coil structure built of 2 long antiparallel a-h helices, whereas the C-terminal domain is a alpha-beta structure. A deletion of the N-terminal arm of the enzyme does not affect the amino acid activation step of the reaction, but reduces dramatically amino-acylation activity. The Kcat/Km value for the mutant enzyme is reduced by more than 4 orders of magnitude, with a nearly 30 fold increased Km value for tRNA(ser). An only slightly truncated mutant form (16 amino acids of the tip of the arm replaced by a glycine) has an intermediate aminoacylation activity. Both mutant synthetases have lost their specificity for tRNA(ser) and charge also non-cognate type 1 tRNA(s). Our results support the hypothesis that class II synthetases have evolved from an ancestral catalytic core enzyme by adding non-catalytic N-terminal or C-terminal tRNA binding (specificity) domains which act as determinants for cognate and anti-determinants for non-cognate tRNAs. | Serine-tRNA Ligase |
Alcohol is a porphyrinogenic agent which may cause disturbances in porphyrin metabolism in healthy persons as well as biochemical and clinical manifestations of acute and chronic hepatic porphyrias. After excessive consumption of alcohol, a temporary, clinically asymptomatic secondary hepatic coproporphyrinuria is observable, which can become persistent in cases of alcohol-induced liver damage. Nowadays, the alcohol-liver-porphyrinuria syndrome is the first to be mentioned in secondary hepatic disturbances of porphyrin metabolism. Acute hepatic porphyrias (acute intermittent porphyria, variegate porphyria and hereditary coproporphyria) are considered to be molecular regulatory diseases, in contrast to non-acute, chronic hepatic porphyria, clinically appearing as porphyria cutanea tarda (PCT). Porphyrins do not accumulate in the liver in acute porphyrias, whereas in chronic hepatic porphyrias they do. Thus, chronic hepatic porphyria is a porphyrin-accumulation disease, whereas acute hepatic porphyrias are haem-pathway-dysregulation diseases, characterized in general by induction of delta-aminolevulinic acid synthase in the liver and excessive stimulation of the pathway without storage of porphyrins in the liver. The clinical expression of acute hepatic porphyrias can be triggered by alcohol, because alcohol augments the inducibility of delta-aminolevulinic acid synthase. In chronic hepatic porphyrias, however, which are already associated with liver damage, alcohol potentiates the disturbance of the decarboxylation of uro- and heptacarboxyporphyrinogen, which is followed by a hepatic accumulation of uro- and heptacarboxyporphyrin and their sometimes extreme urinary excretion. Especially in persons with a genetic deficiency of uroporphyrinogen decarboxylase, but also in patients with the so-called sporadic variety of PCT, alcohol is able to transform an asymptomatic coproporphyrinuria into PCT. Alcohol has many biochemical and clinical effects on porphyrin and haem synthesis both in humans and laboratory animals. Ethanol suppresses the activity of porphobilinogen synthase (synonym: delta-aminolevulinic acid dehydratase), uroporphyrinogen decarboxylase, coproporphyrinogen oxidase and ferrochelatase, whereas it induces the first and rate-limiting enzyme in the pathway, delta-aminolevulinic acid synthase and also porphobilinogen deaminase. Therefore, teetotalism is a therapeutically and prophylactically important measure in all types of hepatic porphyrias. | Coproporphyrinogen Oxidase |
Patients with poor vision screening results should be referred to an ophthalmology subspecialist for further testing to define the refractive error. Refractive errors are influenced by the optical power of the cornea and lens, along with the length of the eye (ie, total of the lens thickness, anterior, and vitreous chamber depth). Refractive errors include myopia, in which the visual image focuses in front of the retina, and hyperopia, in which the visual image focuses behind the retina. Patients with myopia, or nearsightedness, are able to see near objects better than those at a distance. Being outdoors or participation in physical activity outdoors may prevent myopia. Eyeglasses, surgery, and pharmacotherapy also have been studied to correct and prevent progression of myopia. Patients with hyperopia, or farsightedness, have good distance vision but may have more difficulty with reading. Another concern for children with hyperopia is development of strabismus because of refractive error. Eyeglasses and surgery are the management options for hyperopia. | Refractive Errors |
PURPOSE OF REVIEW: Respiratory syncytial virus (RSV) continues to be a major cause of severe lower respiratory tract infection in infants, young children, and older adults. In this review, changes in the epidemiology of RSV during the coronavirus disease 2019 (COVID-19) pandemic are highlighted together with the role which increased molecular surveillance efforts will have in future in assessing the efficacy of vaccines and therapeutics. RECENT FINDINGS: The introduction of nonpharmaceutical intervention (NPIs) strategies during the COVID-19 pandemic between 2020 and 2022 resulted in worldwide disruption to the epidemiology of RSV infections, especially with respect to the timing and peak case rate of annual epidemics. Increased use of whole genome sequencing along with efforts to better standardize the nomenclature of RSV strains and discrimination of RSV genotypes will support increased monitoring of relevant antigenic sites in the viral glycoproteins. Several RSV vaccine candidates based on subunit, viral vectors, nucleic acid, or live attenuated virus strategies have shown efficacy in Phase 2 or 3 clinical trials with vaccines using RSVpreF protein currently the closest to approval and use in high-risk populations. Finally, the recent approval and future use of the extended half-life human monoclonal antibody Nirsevimab will also help to alleviate the morbidity and mortality burden caused by annual epidemics of RSV infections. SUMMARY: The ongoing expansion and wider coordination of RSV molecular surveillance efforts via whole genome sequencing will be crucial for future monitoring of the efficacy of a new generation of vaccines and therapeutics. | Pneumovirus Infections |
Proton pump inhibitors (PPIs) are the gold standard treatment for gastroesophageal reflux disease. In clinical practice, failure of PPIs occurs frequently, and may affect up to 30% of patients in a typical gastroenterology practice. Multichannel impedance monitoring combined with pH monitoring helps to detect nonacid reflux, and if symptoms correlate with these nonacid reflux episodes, nonacid reflux disease can be diagnosed. In contrast to PPIs, reflux inhibitors target transient lower esophageal sphincter relaxations, which are involved in the pathophysiology of reflux disease and may be the appropriate future treatment for nonacid reflux disease. The present article discusses the current understanding of nonacid reflux disease, its diagnosis and treatment. | Baclofen |
The three-domain initiation module PheATE (GrsA) of Bacillus brevis gramicidin S synthetase catalyzes the activation, thiolation and epimerization of L-phenylalanine (L-Phe), the first amino acid incorporated into the decapeptide antibiotic gramicidin S. There are three activated intermediates in the PheATE catalyzed chemical pathway: L-phenylalanyl-adenosine-5'-monophosphate diester (L-Phe-AMP), L-Phe-S-4'-phosphopantetheine(Ppant)- and D-Phe-S-4'-Ppant-acyl enzyme. In this study, we examined PheATE in single-turnover catalysis using rapid chemical quench techniques. Kinetic modeling of the process of disappearance of the substrate L-Phe, transient appearance and disappearance of L-Phe-AMP and the ad seriatim formation and equilibration of the L- and D-Phe-S-Ppant-acyl enzyme adducts allowed evaluation of the microscopic rate constants for the three chemical reactions in the initiation module PheATE. This study provides the first transient-state kinetic analysis of a nonribosomal peptide synthetase (NRPS) module. | Pantetheine |
Hemorrhagic fever with renal syndrome (HFRS), caused by different hantaviruses, is a distinct clinical syndrome endemic in several parts of Asia and Europe. However, the clinical picture can sometimes be indistinguishable from that of other infectious or noninfectious diseases. In this report we describe a clinical case, which is a rare occurrence but is a prime example of the difficulties in the diagnosis of HFRS in areas with a low prevalence of the disease." | Hemorrhagic Fever with Renal Syndrome |
Amacrine cells (ACs) are a diverse class of interneurons that modulate input from photoreceptors to retinal ganglion cells (RGCs), rendering each RGC type selectively sensitive to particular visual features, which are then relayed to the brain. While many AC types have been identified morphologically and physiologically, they have not been comprehensively classified or molecularly characterized. We used high-throughput single-cell RNA sequencing to profile >32,000 ACs from mice of both sexes and applied computational methods to identify 63 AC types. We identified molecular markers for each type and used them to characterize the morphology of multiple types. We show that they include nearly all previously known AC types as well as many that had not been described. Consistent with previous studies, most of the AC types expressed markers for the canonical inhibitory neurotransmitters GABA or glycine, but several expressed neither or both. In addition, many expressed one or more neuropeptides, and two expressed glutamatergic markers. We also explored transcriptomic relationships among AC types and identified transcription factors expressed by individual or multiple closely related types. Noteworthy among these were Meis2 and Tcf4, expressed by most GABAergic and most glycinergic types, respectively. Together, these results provide a foundation for developmental and functional studies of ACs, as well as means for genetically accessing them. Along with previous molecular, physiological, and morphologic analyses, they establish the existence of at least 130 neuronal types and nearly 140 cell types in the mouse retina.SIGNIFICANCE STATEMENT The mouse retina is a leading model for analyzing the development, structure, function, and pathology of neural circuits. A complete molecular atlas of retinal cell types provides an important foundation for these studies. We used high-throughput single-cell RNA sequencing to characterize the most heterogeneous class of retinal interneurons, amacrine cells, identifying 63 distinct types. The atlas includes types identified previously as well as many novel types. We provide evidence for the use of multiple neurotransmitters and neuropeptides, and identify transcription factors expressed by groups of closely related types. Combining these results with those obtained previously, we proposed that the mouse retina contains approximately 130 neuronal types and is therefore comparable in complexity to other regions of the brain. | Amacrine Cells |
OBJECTIVE: The alterations in contractile proteins underlying enhanced Ca(2+)-sensitivity of the contractile apparatus in end-stage failing human myocardium are still not resolved. In the present study an attempt was made to reveal to what extent protein alterations contribute to the increased Ca(2+)-responsiveness in human heart failure. METHODS: Isometric force and its Ca(2+)-sensitivity were studied in single left ventricular myocytes from non-failing donor (n=6) and end-stage failing (n=10) hearts. To elucidate which protein alterations contribute to the increased Ca(2+)-responsiveness isoform composition and phosphorylation status of contractile proteins were analysed by one- and two-dimensional gel electrophoresis and Western immunoblotting. RESULTS: Maximal tension did not differ between myocytes obtained from donor and failing hearts, while Ca(2+)-sensitivity of the contractile apparatus (pCa(50)) was significantly higher in failing myocardium (deltapCa(50)=0.17). Protein analysis indicated that neither re-expression of atrial light chain 1 and fetal troponin T (TnT) nor degradation of myosin light chains and troponin I (TnI) are responsible for the observed increase in Ca(2+)-responsiveness. An inverse correlation was found between pCa(50) and percentage of phosphorylated myosin light chain 2 (MLC-2), while phosphorylation of MLC-1 and TnT did not differ between donor and failing hearts. Incubation of myocytes with protein kinase A decreased Ca(2+)-sensitivity to a larger extent in failing (deltapCa(50)=0.20) than in donor (deltapCa(50)=0.03) myocytes, abolishing the difference in Ca(2+)-responsiveness. An increased percentage of dephosphorylated TnI was found in failing hearts, which significantly correlated with the enhanced Ca(2+)-responsiveness. CONCLUSIONS: The increased Ca(2+)-responsiveness of the contractile apparatus in end-stage failing human hearts cannot be explained by a shift in contractile protein isoforms, but results from the complex interplay between changes in the phosphorylation status of MLC-2 and TnI. | Atrial Myosins |
The immediate prospects of development of radiodiagnostic equipment on the basis of digital systems for medical image representation and processing are considered. Special attention is paid to development of X-ray diagnostic systems." | Radiographic Image Interpretation, Computer-Assisted |
Necrobiotic xanthogranuloma (NXG) is an uncommon granulomatous disease involving the skin and extracutaneous tissues. In its typical clinical presentation, it consists of multiple indurate yellow-brownish plaques or nodules, usually located on the periorbital area. The lesions often are bilateral and symmetric and frequently show tendency to atrophy and ulceration. Most cases are asymptomatic, and oral mucosal erosions are sometimes present. Ophthalmologic complications are observed in many patients, and NXG may involve other extracutaneous sites. Paraproteinemia is closely associated with NXG, demonstrating a monoclonal gammapathy, and other hematologic or lymphoproliferative disorders also may appear in association with NXG. Large areas of degenerated collagen alternating with granulomatous inflammation, multinucleate giant cells, cholesterol clefts, and lymphoid follicles are the most outstanding histopathologic characteristics of NXG. The prognosis for NXG is good, but no curative treatment is available. Chemotherapy with alkylating agents is the most frequently administered treatment, but oral and intralesional corticosteroids, interferon alpha, plasmapheresis, surgical excision, and radiation therapy also have been used for treatment of this disorder, with variable results. | Granuloma |
Radiology's core assets include the production, interpretation, and distribution of quality imaging studies. Second-opinion services and concierge practices in radiology aim to augment traditional services by providing patient-centered and physician-centered care, respectively. Patient centeredness enhances patients' understanding and comfort with their radiology tests and procedures and allows them to make better decisions about their health care. As the fee-for-service paradigm shifts to value-based care models, radiology practices have begun to diversify imaging service delivery and communication to coincide with the American College of Radiology Imaging 3.0 campaign. Physician-centered consultation allows for communication of evidence-based guidelines to assist referring physicians and other providers in making the most appropriate imaging or treatment decision for a specific clinical condition. There are disparate practice models and payment schema for the various second-opinion and concierge practices. This review article explores the current state and payment models of second-opinion and concierge practices in radiology. This review also includes a discussion on the benefits, roadblocks, and ethical issues that surround these novel types of practices. | Concierge Medicine |
The C6 glioma cell line, which expresses beta 1- and beta 2-adrenoceptors at a ratio of 80:20, was used to investigate the durations of action of formoterol at beta 1-adrenoceptors and of salmeterol at both beta 1- and beta 2-adrenoceptors in an attempt to determine whether the sustained duration of action of salmeterol was unique to beta 2-adrenoceptors or, as with formoterol, resulted from its lipophilic nature and partitioning into the bulk lipid of the plasma membrane. In this cell line, formoterol, like the nonselective beta-adrenoceptor agonist isoprenaline, behaved as a potent, full agonist at beta 1-adrenoceptors and did not seem to exhibit a high degree of selectivity for beta 2-adrenoceptors. Salmeterol seemed to stimulate cAMP accumulation in C6 cells predominantly via activation of the subpopulation of beta 2-adrenoceptors. However, at high (micromolar) agonist concentrations, salmeterol also activated beta 1-adrenoceptors, albeit with low potency and efficacy. At high concentrations (30 microM), salmeterol attenuated cAMP responses mediated by activation of beta 1-adrenoceptors by isoprenaline (Kp = 1.6 microM), indicating that salmeterol exhibited a low affinity for beta 1-adrenoceptors in C6 cells. In multiple washout experiments, cAMP responses to isoprenaline and formoterol waned with increasing numbers of washing processes. Therefore, it seemed that formoterol relied on its moderately lipophilic nature to partition into bulk lipid of the plasma membrane to produce sustained activity, particularly at high agonist concentrations. Salmeterol was found to persist at beta 2-adrenoceptors in C6 cells despite washing cell monolayers up to four times. To determine the duration of action of salmeterol at beta 1-adrenoceptors expressed on the same cells, use was made of full/partial agonist interactions. In cells exposed to a single washout of agonist-containing medium, salmeterol (30 microM) lost its ability to attenuate responses to the more efficacious agonist, isoprenaline. This observation provided convincing evidence to support the hypothesis that salmeterol exhibits sustained agonist activity at beta 2-adrenoceptors, but not beta 1-adrenoceptors, expressed on the same cells. Therefore, the sustained activity of salmeterol at beta 2-adrenoceptors seems to be unique and does not result solely from its partitioning into bulk lipid of the plasma membrane. | Amino Alcohols |
PURPOSE: This case report aims to describe a rare manifestation of isolated hypoglossal nerve palsy (HNP) resulting from organophosphate poisoning (OP), specifically organophosphate- induced delayed neuropathy (OPIDN). The primary objective of this case report is to highlight this unusual manifestation and discuss its potential underlying mechanisms, emphasizing the importance of timely diagnosis and appropriate management. CASE REPORT: A 31-year-old male with a history of consuming a commercial chlorpyrifos formulation presented with acute organophosphate poisoning symptoms that improved with appropriate treatment. However, two weeks later, the patient developed neurological deficits (numbness and weakness spreading from the plantar region to the upper limbs) involving the hypoglossal nerve, manifesting as left-sided tongue deviation, fasciculation, and atrophy, resulting in speech and swallowing difficulties. A comprehensive workup ruled out other potential causes of HNP, supporting the link between OPIDN and isolated HNP. Despite regaining limb strength, the patient's speech and swallowing issues persisted, prompting a follow-up visit to our hospital for further management and rehabilitation. CONCLUSION: This case report highlights a unique manifestation of OPIDN, resulting in isolated HNP, a rare phenomenon. The correlation between exposure to chlorpyrifos, acute organophosphate poisoning, and delayed onset of HNP suggests a causative relationship. Prompt diagnosis, appropriate treatment, and timely speech and swallowing rehabilitation are vital for optimizing outcomes in such cases. Further research is needed to understand the mechanisms underlying this selective vulnerability of OPIDN and to develop targeted interventions. | Hypoglossal Nerve Diseases |
Thymoquinone (TQ), the active ingredient of black seed, is a promising anticancer molecule that inhibits cancer cell growth and progression in vitro and in vivo. Despite the promising anticancer activities of TQ, its translation to the clinic is limited by its poor bioavailability and hydrophobicity. As such, we and others encapsulated TQ in nanoparticles to improve its delivery and limit undesirable cytotoxicity. These TQ-nanoparticle formulations showed improved anticancer and anti-inflammatory activities when compared with free TQ. Here, we provide an overview of the various TQ-nanoparticle formulations, highlight their superior efficacy and discuss up-to-date solutions to further enhance TQ bioavailability and anticancer activity, thus improving potential for clinical translation. | Benzoquinones |
Folate receptor alpha (FRalpha) came into focus as an anticancer target many decades after the successful development of drugs targeting intracellular folate metabolism, such as methotrexate and pemetrexed. Binding to FRalpha is one of several methods by which folate is taken up by cells; however, this receptor is an attractive anticancer drug target owing to the overexpression of FRalpha in a range of solid tumours, including ovarian, lung and breast cancers. Furthermore, using FRalpha to better localize effective anticancer therapies to their target tumours using platforms such as antibody-drug conjugates, small-molecule drug conjugates, radioimmunoconjugates and, more recently, chimeric antigen receptor T cells could further improve the outcomes of patients with FRalpha-overexpressing cancers. FRalpha can also be harnessed for predictive biomarker research. Moreover, imaging FRalpha radiologically or in real time during surgery can lead to improved functional imaging and surgical outcomes, respectively. In this Review, we describe the current status of research into FRalpha in cancer, including data from several late-phase clinical trials involving FRalpha-targeted therapies, and the use of new technologies to develop FRalpha-targeted agents with improved therapeutic indices. | Folate Receptor 1 |
Sphingosine 1-phosphate (S1P) is a bioactive sphingolipid that is critically involved in the embryonic development of the cardiovascular and central nervous systems. In the adult, S1P can produce cytoskeletal re-arrangements in many cell types to regulate immune cell trafficking, vascular homeostasis and cell communication in the central nervous system. S1P is contained in body fluids and tissues at different concentrations, and excessive production of the pleiotropic mediator at inflammatory sites may participate in various pathological conditions. Gene deletion studies and reverse pharmacology (techniques aiming to identify both ligands and function of receptors) provided evidence that many effects of S1P are mediated via five G-protein-coupled S1P receptor subtypes, and novel therapeutic strategies based on interaction with these receptors are being initiated. The prototype S1P receptor modulator, FTY720 (fingolimod), targets four of the five S1P receptor subtypes and may act at several levels to modulate lymphocyte trafficking via lymphocytic and endothelial S1P1 and, perhaps, other inflammatory processes through additional S1P receptor subtypes. A recently completed Phase II clinical trial suggested that the drug may provide an effective treatment of relapsing-remitting multiple sclerosis. FTY720 is currently being evaluated in larger-scale, longer-term, Phase III studies. This review provides an overview on S1P activities and S1P receptor function in health and disease, and summarizes the clinical experience with FTY720 in transplantation and multiple sclerosis. | Sphingosine |
To lose one's sense of what it means to be human reflects a profound form of loss. Recent research in the study of dehumanization highlights that the loss of humanness can be experienced at the hands of close others. Moreover, acts of dehumanization can take many forms in close relationships. In this paper, we review the emerging literature on the study of dehumanization within interpersonal relationships, placing a specific emphasis on adult romantic relationships. We situate our review of the literature within a newly developed model of interpersonal dehumanization. This model outlines how many destructive relationship behaviors reflect forms of dehumanization, which can result in a vast array of personal and relational losses. | Dehumanization |
Cytoplasmic organelles with an acidic luminal pH include vacuoles, coated vesicles, lysosomes, the Golgi apparatus, and synaptic vesicles. Acidic compartments are also known outside specialized cells such as osteoclasts. The unique acidic pH is formed by V-ATPase (Vacuolar type ATPase), other ion transporters, and the buffering action of proteins inside the organelles. V-ATPase hydrolyzes ATP and transports protons inside an organelle or extracellular compartment. We have summarized recent progress on mouse V-ATPases and their varying localizations together with their mechanism emphasizing similarities with F-type ATPases." | Vacuolar Proton-Translocating ATPases |
The recruitment of the lysosomal cathepsins B (CAB), L (CAL) and D (CAD) as luminal digestive enzymes was investigated in 3 species of beetles. Gene expression was determined by RNA-seq in different regions of the midgut and in the carcasses from the transcriptomes of Dermestes maculatus, Tenebrio molitor and Zabrotes subfasciatus. These data together with phylogenetic analyses, allowed us to identify the sequences of the gene coding for digestive and lysosomal CABs, CADs and CALs in T. molitor and Z. subfasciatus and observe the absence of digestive cathepsins in D. maculatus. Comparisons of structures based on the overall similarity of modelled structures were performed and subsite residues in the lysosomal and digestive CALs were identified by molecular docking. The data showed that S2 subsites are very variable, probably as an adaption to a luminal digestive role. The survey of sequences of the gene coding for cathepsins in the genomes of 13 beetle species from different phylogenetic groups showed that expansion of CAL and CAB genes occurred only in the Cucujiformia clade. Several digestive CABs have a reduced occluding loop, probably to act as digestive enzymes. Pollen-feeding was proposed to be the selective pressure to recruit cathepsins as digestive enzymes in Cucujiformia beetles. | Cathepsins |
Pulse diagnosis is a convenient, inexpensive, painless, and non-invasive diagnosis method. Quantifying pulse diagnosis is to acquire and record pulse waveforms by a set of sensor firstly, and then analyze these pulse waveforms. However, respiration and artifact motion during pulse waveform acquisition can introduce baseline wander. It is necessary, therefore, to remove the pulse waveform's baseline wander in order to perform accurate pulse waveform analysis. This paper presents a wavelet-based cascaded adaptive filter (CAF) to remove the baseline wander of pulse waveform. To evaluate the level of baseline wander, we introduce a criterion: energy ratio (ER) of pulse waveform to its baseline wander. If the ER is more than a given threshold, the baseline wander can be removed only by cubic spline estimation; otherwise it must be filtered by, in sequence, discrete Meyer wavelet filter and the cubic spline estimation. Compared with traditional methods such as cubic spline estimation, morphology filter and Linear-phase finite impulse response (FIR) least-squares-error digital filter, the experimental results on 50 simulated and 500 real pulse signals demonstrate the power of CAF filter both in removing baseline wander and in preserving the diagnostic information of pulse waveforms. This CAF filter also can be used to remove the baseline wander of other physiological signals, such as ECG and so on. | Pulse |
Purpose This study was designed to examine the association of dosage and effects of Sound Production Treatment (SPT) for acquired apraxia of speech. Method Treatment logs and probe data from 20 speakers with apraxia of speech and aphasia were submitted to a retrospective analysis. The number of treatment sessions and teaching episodes was examined relative to (a) change in articulation accuracy above baseline performance, (b) mastery of production, and (c) maintenance. The impact of practice schedule (SPT-Blocked vs. SPT-Random) was also examined. Results The average number of treatment sessions conducted prior to change was 5.4 for SPT-Blocked and 3.9 for SPT-Random. The mean number of teaching episodes preceding change was 334 for SPT-Blocked and 179 for SPT-Random. Mastery occurred within an average of 13.7 sessions (1,252 teaching episodes) and 12.4 sessions (1,082 teaching episodes) for SPT-Blocked and SPT-Random, respectively. Comparisons of dosage metric values across practice schedules did not reveal substantial differences. Significant negative correlations were found between follow-up probe performance and the dosage metrics. Conclusions Only a few treatment sessions were needed to achieve initial positive changes in articulation, with mastery occurring within 12-14 sessions for the majority of participants. Earlier occurrence of change or mastery was associated with better follow-up performance. Supplemental Material https://doi.org/10.23641/asha.12592190. | Apraxias |
To evaluate the dual-isotope Schilling test for the diagnosis of pernicious anemia or malabsorption syndrome, 65 studies were selected for clinical correlation. Criteria for pernicious anemia included mean corpuscular volume greater than 100 cu micrometer, serum B12 greater than 100 ng/l, megaloblastic marrow, achlorhydria, reticulocytes greater than 5% on B12 therapy, atrophic gastritis, and elevated serum antibodies to parietal cells or intrinsic factor. Criteria for malabsorption syndrome included: decreased serum B12, folate, and carotene; increased fecal fat; abnormal D-xylose absorption; abnormal radiographic and biopsy findings. 58Co-cyanocobalamin and 57Co-cyanocobalamin bound to intrinsic factor were given orally to fasting patients; 1 mg of nonradioactive B12 was injected intramuscularly within two hours. Aliquots of 24-hour urine samples were counted. If the excretion of 58Co was less than 7% and the 57Co/58Co ratio was greater than 1.7, the test indicated pernicious anemia; a ratio less than 1.7 indicated malabsorption syndrome. Sensitivity, specificity, and accuracy of the dual-isotope Schilling test were 83%, 98%, and 94% for pernicious anemia, and 67%, 90%, and 86% for malabsorption syndrome, respectively. | Schilling Test |
Studies with inhibitors have implicated protein kinase C (PKC) in the adhesive functions of integrin alpha(IIb)beta(3) in platelets, but the responsible PKC isoforms and mechanisms are unknown. Alpha(IIb)beta(3) interacts directly with tyrosine kinases c-Src and Syk. Therefore, we asked whether alpha(IIb)beta(3) might also interact with PKC. Of the several PKC isoforms expressed in platelets, only PKC beta co-immunoprecipitated with alpha(IIb)beta(3) in response to the interaction of platelets with soluble or immobilized fibrinogen. PKC beta recruitment to alpha(IIb)beta(3) was accompanied by a 9-fold increase in PKC activity in alpha(IIb)beta(3) immunoprecipitates. RACK1, an intracellular adapter for activated PKC beta, also co-immunoprecipitated with alpha(IIb)beta(3), but in this case, the interaction was constitutive. Broad spectrum PKC inhibitors blocked both PKC beta recruitment to alpha(IIb)beta(3) and the spread of platelets on fibrinogen. Similarly, mouse platelets that are genetically deficient in PKC beta spread poorly on fibrinogen, despite normal agonist-induced fibrinogen binding. In a Chinese hamster ovary cell model system, adhesion to fibrinogen caused green fluorescent protein-PKC beta I to associate with alpha(IIb)beta(3) and to co-localize with it at lamellipodial edges. These responses, as well as Chinese hamster ovary cell migration on fibrinogen, were blocked by the deletion of the beta(3) cytoplasmic tail or by co-expression of a RACK1 mutant incapable of binding to beta(3). These studies demonstrate that the interaction of alpha(IIb)beta(3) with activated PKC beta is regulated by integrin occupancy and can be mediated by RACK1 and that the interaction is required for platelet spreading triggered through alpha(IIb)beta(3). Furthermore, the studies extend the concept of alpha(IIb)beta(3) as a scaffold for multiple protein kinases that regulate the platelet actin cytoskeleton. | Protein Kinase C beta |
AIMS: To longitudinally explore the symptom experience of Chinese patients with Crohn's disease within the first year following their diagnosis. DESIGN: A longitudinal qualitative study. METHOD: Eighteen newly diagnosed Chinese patients with Crohn's disease were recruited through purposive sampling. Semi-structured interviews were conducted at four time points: soon after diagnosis, 3, 6 and 12 months post-diagnosis. Data were collected between January 2021 and February 2022. Conventional content analysis was used for data analysis of each time point. Afterwards, the data of each time point were compared longitudinally. COREQ checklist was followed. RESULTS: Three themes and eight sub-themes were formed through analysis: feelings towards symptoms (symptoms make me feel uneasy, symptoms make me feel inferior and symptoms make me feel helpless); acceptability of symptoms (difficult to accept, have to accept, be able to accept); functions of symptoms (assessing disease conditions and treatment effects, warning of disease management). CONCLUSIONS: Overall, the negative emotions related to symptoms gradually decreased over time, and the patient's acceptance of symptoms increased within the first year following diagnosis. In addition, when the disease was in remission after treatment, the warning function of symptoms gradually weakened. IMPACT: The process of how patients accept their symptoms found in this study provides a basis for nurses to improve patients' acceptance of symptoms and reduce their symptom-related negative emotions. This study also emphasizes the phenomenon that patients gradually ignore some symptoms with their increased acceptance level, which warrants additional health education to strengthen their awareness of self-management. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution was required to design or undertake this study. Patients contributed only to the data collection and member checking. | Crohn Disease |
AIDS-related human cytomegalovirus (HCMV) retinitis remains a major ophthalmologic problem worldwide. Although this sight-threatening disease is well characterized clinically, many pathogenic issues remain unresolved, among them a basic understanding of the relative roles of cell death pathways during development of retinal tissue destruction. Using an established model of experimental murine cytomegalovirus (MCMV) retinitis in mice with retrovirus-induced immunosuppression (MAIDS), we initially investigated MCMV-infected eyes for evidence of apoptosis-associated molecules in mice with MAIDS of 4 weeks' (MAIDS-4) and 10 weeks' (MAIDS-10) duration, which were resistant and susceptible to retinal disease, respectively, but which harbored equivalent amounts of infectious MCMV. Whereas MCMV-infected eyes of MAIDS-4 mice showed little evidence of apoptosis-associated molecules, MCMV-infected eyes of MAIDS-10 mice showed significant amounts of tumor necrosis factor alpha (TNF-alpha), TNF receptors 1 and 2, active caspase 8, active caspase 3, TNF-related apoptosis-inducing ligand (TRAIL), TRAIL-R(DR5), Fas, and Fas ligand mRNAs and/or proteins, all detected at peak amounts prior to development of most severe retinal disease. Immunohistochemical staining showed macrophages, granulocytes (neutrophils), Muller cells, and microglial cells as TNF-alpha sources. Remarkably, quantification of apoptosis by terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) assay suggested that apoptosis contributed minimally to retinal disease in MCMV-infected eyes of MAIDS-10 mice. Subsequent studies demonstrated that MCMV-infected eyes of MAIDS-10 mice, but not MAIDS-4 mice, showed evidence of significant increases in molecules associated with two additional cell death pathways, necroptosis (receptor-interacting protein 1 [RIP1] and RIP3 mRNAs) and pyroptosis (caspase 1, interleukin 1beta [IL-1beta], and IL-18 mRNAs). We conclude that apoptosis, necroptosis, and pyroptosis participate simultaneously during MAIDS-related MCMV retinitis, and all may play a role during AIDS-related HCMV retinitis." | Murine Acquired Immunodeficiency Syndrome |
Keloid scars are an idiopathic result of cuts, bruises, lacerations and often from surgical incisions. Medical therapy has been used with some results, but often surgical excision is necessary when the keloids are located in areas of exposed skin. Often skin grafting is necessary. The problem of keloid formation is more common in African Americans and Asians in the United States. Because surgery of these lesions is sometimes considered cosmetic by HMOs and other insurance carriers, there exists a dispute between the medical profession and insurance carriers regarding the medical necessity of surgery. We have operated on many keloids in our practice; however, the case report we are presenting is a unusual and rare case of giant keloid formation requiring extensive surgery and x-ray therapy. | Acne Keloid |
In many pathologic circumstances, quantitative mRNA expression levels are important for evaluation of possible genome mutations. The development of real-time polymerase chain reaction (RT-PCR) technology has facilitated the realization of nucleic acid quantification. Potentially, quantitative PCR offers a number of advantages over traditional methods because it permits the use of small amounts of genetic material. In the present study, we optimize a RNA purification technique on specimens that are formalin-fixed, paraffin-embedded and we examine prolonged formalin fixation effects on quantitative RT-PCR analysis. We compared RNA levels with 70 colic mucosa samples using the cyclooxygenase 2 gene as marker. The difference in amplification successes between formalin-fixed tissues and formalin-fixed, paraffin-embedded tissues was not statistically significant. Moreover, we compared the expression of formalin-fixed samples with the expression of each fresh tissue. Wilcoxon Mann-Whitney test shows that only the difference in the expression levels of 1- or 3-hour formalin-fixed samples is not statistically significant with respect to other fixation times. We found that the mRNA can be reliably extracted from formalin fixed, paraffin-embedded tissue sections but that prolonged formalin fixation produces different results in quantitative RT-PCR. It can be related to difference in RNA sequences length and the generation of secondary structures that are more susceptible to the prolonged formalin fixation. We suppose that the paraffin do not influence the RNA extraction yield because there are no statistical significant differences between amplification success of formalin-fixed tissues and paraffin-embedded tissues. Therefore, in relative expression quantization, we confirm that it is appropriate to use specimens with same protocols and time for formalin fixation. | RNA, Neoplasm |
Malignant peripheral nerve sheath tumour (MPNST) is an aggressive and uncommon cancer developing in the peripheral nerve sheath. Primary cardiac MPNST is an extremely rare finding, with no specific imaging and clinical characteristics. Only a handful of cases have been reported in the literature; thus, little is still known about them. Cardiac computed tomography (CT) and cardiac magnetic resonance imaging (CMRI) are important means of assessing cardiac morphology and function. The preferred course of treatment for this pathology is by full surgical resection of the tumour, with negative (clear) margins, followed by adjuvant radiotherapy and chemotherapy. We present the case of a 42-year-old woman with no significant cardiovascular symptoms who was incidentally diagnosed during routine transthoracic echocardiography (TTE) with a cardiac mass located in the left ventricle. | Neurofibrosarcoma |
An increase in global violence has forced the displacement of more than 70 million people, including 26 million refugees and 3.5 asylum seekers. Refugees and asylum seekers face serious socioeconomic and healthcare barriers and are therefore particularly vulnerable to physical and mental health risks, which are sometimes exacerbated by immigration policies and local social discriminations. Calls for a strong evidence base for humanitarian action have encouraged conducting research to address the barriers and needs of refugees and asylum seekers. Given the role of epigenetics factors to mediate the effect of psychological and environmental exposures, epigenetic modifications have been used as biomarkers for life adversity and disease states. Therefore, epigenetic research can be potentially beneficial to address some of the issues associated with refugees and asylum seekers. Here, we review the value of previous and ongoing epigenetic studies with traumatized populations, explore some of the ethical challenges associated with epigenetic research with refugees and asylees and offer suggestions to address or mitigate some of these challenges. Researchers have an ethical responsibility to implement strategies to minimize the harms and maximize the short and long-term benefits to refugee and asylee participants. | Epigenesis, Genetic |
The human skin holds the full machinery for pro-opiomelanocortin processing. The alpha-melanocyte-stimulating hormone (alpha-MSH)/melanocortin-1-receptor cascade has been implicated as a major player via the cAMP signal in the control of melanogenesis. Only very recently the beta-endorphin/mu-opiate receptor signal has been added to the list of regulators of melanocyte dendricity and melanin formation. In this context it was reported that (6R)-l-erythro-5,6,7,8-tetrahydrobiopterin (6BH(4)) can act as an allosteric inhibitor of tyrosinase, the key enzyme in melanogenesis, and this inhibition is reversible by both alpha- and beta-MSH. It was also shown earlier that 7BH(4), the isomer of 6BH(4), is twice as active in this inhibition reaction. However, as yet it is not known whether 7BH(4) is indeed present in loco in the melanosome. We here provide evidence that this isomer is present in this organelle in a concentration range up to 50 x 10(-6) M. Determination of beta-MSH in melanosomal extracts yielded 10 pg/mg protein. Moreover, we demonstrate reactivation of the 7BH(4)/tyrosinase inhibitor complex by beta-MSH, whereas alpha-MSH failed to do so. Furthermore, we show intra-melanosomal l-dopa formation from dopachrome by 7BH(4) in a concentration range up to 134 x 10(-6) M. Based on these results, we propose a new receptor-independent mechanism in the control of tyrosinase/melanogenesis by beta-MSH and the pterin 7BH(4). | beta-MSH |
A 6-year-old breeding female spectacled owl (Pusilatrix perspicillata) was presented for a soft, fluid-filled, spherical mass under the neck that had been increasing in size over the previous 3 days. Results of a fine-needle aspirate of the mass showed clear, pale-yellow fluid with a total protein of 12.6 g/L. Cytologic examination revealed erythrocytes, moderate numbers of heterophils, and numerous foamy mononuclear cells against a mucoid background. Macroscopically, the mass appeared to be attached firmly to the esophagus. The mass was excised surgically and submitted for histopathologic examination. The lesion comprised a circumscribed, fibrous-encapsulated multilocular cyst, lined by plump, goblet-type, cuboidal epithelial cells lying in abundant mucinous matrix. Findings were consistent with a mucocele of the esophageal mucosal gland. Excision was considered curative based on follow-up 6 months after initial presentation. To our knowledge, this is the first report of this condition in Strigiformes and indicates that mucocele should be included in the differential diagnosis of cervical masses in birds. | Bird Diseases |
Photovoltaic modules (or panels) are important power generators with limited lifespans. The modules contain known pollutants and valuable materials such as silicon, silver, copper, aluminum and glass. Thus, recycling such waste is of great importance. To date, there have been few published studies on recycling silver from silicon photovoltaic panels, even though silicon technology represents the majority of the photovoltaic market. In this study, the extraction of silver from waste modules is justified and evaluated. It is shown that the silver content in crystalline silicon photovoltaic modules reaches 600g/t. Moreover, two methods to concentrate silver from waste modules were studied, and the use of pyrolysis was evaluated. In the first method, the modules were milled, sieved and leached in 64% nitric acid solution with 99% sodium chloride; the silver concentration yield was 94%. In the second method, photovoltaic modules were milled, sieved, subjected to pyrolysis at 500 degrees C and leached in 64% nitric acid solution with 99% sodium chloride; the silver concentration yield was 92%. The first method is preferred as it consumes less energy and presents a higher yield of silver. This study shows that the use of pyrolysis does not assist in the extraction of silver, as the yield was similar for both methods with and without pyrolysis. | Nitric Acid |
A Gram-stain-negative, aerobic, non-motile, non-spore-forming bacterium, strain 0511ARD5E5T, was isolated from an air sample collected in Ardales Cave (Malaga, Spain). Strain 0511ARD5E5T grew at 4-37 degrees C and in the presence of 0-4 % (w/v) NaCl [optimally at 25 degrees C and with 1 % (w/v) NaCl]. Cells were catalase- and oxidase-positive. The major respiratory quinone was ubiquinone-10. The predominant fatty acids were C18:1omega7c and C16:0. The DNA G+C content was 63.2 mol%. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain 0511ARD5E5T was a member of the genus Paracoccus and was related most closely to Paracoccus aminophilus DSM 8538T and Paracoccus marinus CIP 108500T (96.93 and 96.92 % similarity, respectively). Strain 0511ARD5E5T exhibited DNA-DNA relatedness of 47 % to P. aminophilus DSM 8538T and 31 % to P. marinus CIP 108500T. Chemotaxonomic, phenotypic and phylogenetic analyses indicated that strain 0511ARD5E5T represents a novel species of the genus Paracoccus, for which the name Paracoccus cavernae sp. nov. is proposed. The type strain is 0511ARD5E5T (=LMG 27962T=CECT 8482T). | Paracoccus |
To develop a model to predict the efficacy and adversity of class I antiarrhythmic drugs, intraventricular conduction time (IVCT), coronary blood flow (CBF), developed tension of papillary muscle (DT) and idioventricular automaticity rate (VR) were measured following drug administration in an isolated canine papillary muscle preparation cross-circulated with the heparinized blood of a donor dog. Tetrodotoxin, the prototypic fast Na+ channel blocker, and class I drugs increased IVCT and CBF, but decreased DT and VR, in a dose-dependent manner. The profiles of known class I drugs, procainamide, disopyramide, lidocaine, mexiletine and flecainide were similar, but the potencies of each drug were different. Two new class I drugs, ME3202 and AN-132, were also tested and found to have effects that were similar to that of tetrodotoxin. There was a good correlation between the doses of drugs prolonging IVCT by 50% and the canine antiarrhythmic plasma concentrations in our previous study. This model can also be used to estimate the use-dependency and the kinetics of use-dependent sodium channel block; however, it is not suitable for extensive investigation of cellular and molecular mechanisms. Thus, the use of this model facilitates the comparison of multiple cardiac effects of class I drugs and may be an effective way to better assess new antiarrhythmic drugs. | Cross Circulation |
Radiation pneumonitis (RP) is the most common complication of radiotherapy for thoracic tumours. The aim of this study was to evaluate the significance of pulmonary surfactant proteins (SP)-A and SP-D as new serum markers for RP. Twenty-five patients with lung tumour, who had received radiotherapy, were studied. At the completion of radiotherapy, the presence of RP was judged by chest plain radiography and chest high resolution computed tomography (HRCT). RP findings detected on chest plain radiography were seen in only three of 12 patients in whom RP was detected by HRCT. Nevertheless, both SP-A and SP-D concentrations in sera from the patients with RP were significantly higher than those from the 13 patients without RP (p = 0.0065, p = 0.0011, respectively). As with SP-A, ratios of SP-D at the completion, compared to at the initiation (1 week post/pre ratio), were also significantly higher in patients with RP than in patients without RP. When a post/pre ratio > 1.6 was considered positive, the SP-A and SP-D assays showed an 83% and 85% specificity, respectively. In conclusion, serum assays of surfactant proteins A and D may be of diagnostic value for detection of radiation pneumonitis, even when the radiographic change is faint. | Radiation Pneumonitis |
BACKGROUND: Poor adherence to ABL tyrosine kinase inhibitors (ABL TKIs) is associated with reduced treatment efficacy and increased healthcare costs. To examine the hazards associated with poor adherence, we implemented failure mode and effects analysis (FMEA). METHODS: We surveyed 54 chronic myeloid leukemia (CML) patients treated at Saga University Hospital from October 2012 to May 2014. The survey consisted of items regarding the type of ABL TKI used, adherence to ABL TKIs, the appearance of adverse effects, utilisation of the high cost medical care benefit system, and factors affecting adherence. Four factors that likely affected adherence were identified, including the level of understanding of ABL TKIs treatment outcomes, adverse effects, the high cost of medications, and careless slips in the taking of medicine. Results of the survey were analysed by FMEA. RESULTS: The risk priority number was highest for careless slips in the taking of medicine at 7.0 +/- 1.0 (mean +/- SEM), followed in descending order by the inadequate understanding of treatment outcomes (4.9 +/- 0.6), adverse effects (3.8 +/- 0.8), and high medication cost (2.2 +/- 0.5). Thus, the prevention of careless slips was the most important factor affecting adherence to ABL TKIs. Contrary to our preoccupation, FMEA revealed that high medication cost was the lowest risk factor for poor adherence. This finding may be attributed to the high utilisation (96.3 %) of the high cost medical care benefit system. CONCLUSION: These findings suggest that an inadequate medication-taking habit such as careless slips may represent a potential target to improve and maximize adherence in CML patients." | Healthcare Failure Mode and Effect Analysis |
As part of an ongoing study developing and evaluating the use of programme budgeting (PB) and marginal analysis (MA) within purchasing organizations, conducts a survey of a health authorities' requirements of a decision-making tool based on PBMA. PB is a management decision-making system. It provides a summary of resource use categorized according to the programme or end product to which it applies. This explicit description of current activities focuses attention on competition for resources among programmes and on the effectiveness of resource use within programmes. MA is an economist's tool to evaluate options for changing the balance of resource use between or within programmes. Finds general support for PBMA techniques, although this waned with the higher functions of the tool. There was consensus that a health authority ought to know fundamentals like, for example, what proportion it spends on tackling coronary heart disease; and a majority view that PB will assist in revealing the key margins for service review. | Group Purchasing |
Studies were conducted to define the subcellular localization of endogenous retinoids (vitamin A), retinoid-binding proteins, and acyl-CoA:retinol acyltransferase (ARAT) in liver and to determine whether their distributions were affected by hepatic vitamin A content. Quantitative subcellular fractionation techniques were used. Rats were fed purified diets either containing or lacking vitamin A to obtain animals with total retinoid stores ranging from 0.5 to 172 micrograms of retinol equivalent per gram of liver. Liver homogenates were fractionated by differential centrifugation to yield nuclear (N), mitochondrial-lysosomal (ML), microsomal (P), and high-speed supernatant (S) fractions. N, ML, and P were washed two more times by resuspension and centrifugation to remove constituents bound nonspecifically. S was further resolved into "floating lipid" and underlying "cytosol" by prolonged ultracentrifugation. The distributions of marker constituents were not affected by vitamin A status. Most of the retinyl ester in the liver was recovered in the S fraction where it was entirely (greater than 95%) associated with floating lipid. About half of the total free retinol was also recovered in the S fraction, but it was mostly (2/3) associated with cytosol per se. A substantial portion (30%) of the free retinol was recovered in the 3 X -washed microsomal (P) fraction. Sufficient binding capacity for retinol was present in both P (as retinol-binding protein) and S (as cellular retinol-binding protein) to quantitatively account for the amounts of free retinol present in the two fractions. ARAT activity in the liver was distributed among the subcellular fractions in a manner identical with an endoplasmic reticulum marker enzyme (NADPH-cytochrome C reductase).(ABSTRACT TRUNCATED AT 250 WORDS)" | Retinol O-Fatty-Acyltransferase |
A case is described in which a patient developed acute pancreatitis following an overdose of amoxapine and procyclidine. Pancreatitis is not at this time a recognized complication of the use or abuse of these two drugs. Other drugs were used in the medical management of the complications of the overdose, but none of these are drugs known to be associated with pancreatitis. Amoxapine is probably, but not certainly the cause of the pancreatitis. Possible mechanisms for this unusual and serious complication are described. | Procyclidine |
PURPOSE OF REVIEW: A diverse range of surgical approaches are now used for glaucoma management. This review compares the reported rates of serous choroidal effusion and suprachoroidal hemorrhage after various glaucoma surgical procedures. As these complications can be visually devastating, we summarize the current literature on prevention strategies and management. RECENT FINDINGS: Trabeculectomy remains one of the most effective and widely used glaucoma surgeries, but it is also associated with a significant rate of complications, including serous choroidal effusion and suprachoroidal hemorrhage. Alternative surgical techniques for glaucoma management are increasingly utilized due in part to their lower rate of associated complications. Prevention measures for serous choroidal effusion and suprachoroidal hemorrhage include the recognition of patient risk factors and careful selection of glaucoma surgical technique. Management options include observation, medications, office-based procedures, and surgical interventions directed at maximizing patient outcomes. SUMMARY: Familiarity with reported rates of postoperative choroidal effusions, patient risk factors, and management strategies will aid in reducing the frequency of these complications and in improving patient care. | Choroid Hemorrhage |
Smooth muscle contraction is triggered when Ca(2+)/calmodulin-dependent myosin light chain kinase (MLCK) phosphorylates the regulatory light chain of myosin (RLC(20)). However, blood vessels from Mlck-deficient mouse embryos retain the ability to contract, suggesting the existence of additional regulatory mechanisms. We showed that the p90 ribosomal S6 kinase 2 (RSK2) also phosphorylated RLC(20) to promote smooth muscle contractility. Active, phosphorylated RSK2 was present in mouse resistance arteries under normal basal tone, and phosphorylation of RSK2 increased with myogenic vasoconstriction or agonist stimulation. Resistance arteries from Rsk2-deficient mice were dilated and showed reduced myogenic tone and RLC(20) phosphorylation. RSK2 phosphorylated Ser(19) in RLC in vitro. In addition, RSK2 phosphorylated an activating site in the Na(+)/H(+) exchanger (NHE-1), resulting in cytosolic alkalinization and an increase in intracellular Ca(2+) that promotes vasoconstriction. NHE-1 activity increased upon myogenic constriction, and the increase in intracellular pH was suppressed in Rsk2-deficient mice. In pressured arteries, RSK2-dependent activation of NHE-1 was associated with increased intracellular Ca(2+) transients, which would be expected to increase MLCK activity, thereby contributing to basal tone and myogenic responses. Accordingly, Rsk2-deficient mice had lower blood pressure than normal littermates. Thus, RSK2 mediates a procontractile signaling pathway that contributes to the regulation of basal vascular tone, myogenic vasoconstriction, and blood pressure and may be a potential therapeutic target in smooth muscle contractility disorders. | Smooth Muscle Myosins |
OBJECTIVE: The purpose of this study was to evaluate the MR spectrum and MR cholangiographic imaging findings of clonorchiasis. MATERIALS AND METHODS: We reviewed 26 patients with confirmed clonorchiasis by either stool tests (n=24) or surgery (n=2). MR imaging was performed on a 1.5 T system (GE Medical Systems, Milwaukee, WI) with a torso coil. Axial T1- and T2-weighted, gadolinium-enhanced dynamic images and MR cholangiography were obtained. Image analyses were used to identify abnormalities of the intrahepatic and extrahepatic bile ducts and the presence of hepatobiliary malignancy. All MR examinations were reviewed by the consensus of two abdominal radiologists. RESULTS: Intrahepatic bile duct abnormalities were seen in 23 (89%) of the 26 patients. The most common finding was mild dilatation of the intrahepatic bile duct which was found in 21 (81%). Too many intrahepatic ducts" were found in 16(62%), wall enhancement and thickening in 21 (81%) and filling defects and ductal stricture in the intrahepatic bile duct in 6 (24%) and 3 (12%) patients, respectively. Extrahepatic ductal dilation was found in 5 (19%) and 9 (35%) revealed hepatobiliary malignancy. CONCLUSION: MR imaging revealed various findings of clonorchiasis, including dilatation, wall enhancement, stricture of the intrahepatic ducts and filling defect within the intrahepatic bile duct." | Clonorchiasis |
Targeted drug delivery has been extensively studied in the last decade, whereas both passive and active targeting strategies still face many challenges, such as off-target drug release. Light-responsive drug delivery systems have been developed with high controllability and spatio-temporal resolution to improve drug efficacy and reduce off-target drug release. Photoremovable protecting groups are light-responsive moieties that undergo irreversible photocleavage reactions upon light irradiation. They can be covalently linked to the molecule of interest to control its structure and function with light. In this review, we will summarize recent applications of photocleavage technologies in nanoparticle-based drug delivery for precise targeting and controlled drug release, with a highlight of strategies to achieve long-wavelength light excitation. A greater understanding of these mechanisms and emerging studies will help design more efficient photocleavage-based nanosystems to advance photoresponsive drug delivery. | Drug Liberation |
Head and neck cancer, including oral squamous cell carcinoma (OSCC), ranks as the sixth most common malignancy worldwide. Overall 5-year survival rates of OSCC have not significantly improved during the past 3 decades and the 5-year survival rate is less than 50%. Several invasion grading systems have been employed in OSCC, however, their utility is still controversial. HuD belongs to the Hu protein family and acts as an RNA-binding protein involved in mRNA stability and translational regulation. Although HuD has a pivotal role for neuronal differentiation, the functional role of HuD in OSCCs is still unclear. In this study, we examined HuD expression in 82 OSCC cases. Expression of HuD was observed in 36.6% of OSCCs and significantly associated with histological differentiation, nodal metastasis and mode of invasion. HuD expression in high-metastatic HSC3 cells was higher than in low-metastatic HSC4 cells, and inhibition of invasion ability and activation of caspase-3 were shown by HuD siRNA-treated HSC3 cells. Furthermore, we clarified that HuD regulates expression of vascular endothelial growth factor (VEGF)-A, VEGF-D, matrix metallopeptidase (MMP)-2 and MMP-9. These results suggest that HuD is a useful diagnostic and therapeutic target in OSCCs. | ELAV-Like Protein 4 |
INTRODUCTION: Eurycoma longifolia Jack (EL), profoundly recognised as 'Tongkat Ali', is a medicinal herb originating from Southeast Asia. It is commonly used in traditional 'antiageing' treatments to address decreased energy, mood, libido and hormonal imbalances. While the benefits of EL have been extensively studied among the male population, less attention has been given to its effects on women. Menopause can impact the overall well-being of middle-aged women and incorporation of herbal supplements can aid them in managing the menopausal symptoms. METHODS AND ANALYSIS: This 12-week randomised double-blind, placebo-controlled, parallel-group study aims to evaluate the efficacy of the standardised water extract of EL known as Physta in increasing the quality of life of perimenopausal and postmenopausal women. The study involves 150 women aged 40-55 years who score more than 61 on the Menopause-Specific Quality of Life (MENQOL) assessment. These participants will be randomised into three groups, receiving Physta at either 50 mg or 100 mg or a placebo. The outcomes measures include mood state, quality of life, fatigue, sleep quality, sexual function and pain score assessed using Profile of Mood State, MENQOL, Chalder Fatigue Scale, Pittsburgh Sleep Quality Index, Female Sexual Function Index and the Brief Pain Inventory questionnaires, respectively. The secondary outcome of the study includes full blood analysis, urine analysis, female reproductive hormone profiling, inflammatory and oxidative stress biomarkers analysis. ETHICS AND DISSEMINATION: The research protocol of the study was reviewed and approved by the Research Ethics Committee of Universiti Kebangsaan Malaysia (UKM/PPI/111/8/JEP-2021-898). The findings will be disseminated to participants, healthcare professionals and researchers via conference presentations and peer-reviewed publications. TRIAL REGISTRATION NUMBER: ACTRN12622001341718. | Eurycoma |
Like it or not, workforce reduction has become a strategy to achieve or maintain financial solvency. As nurse leader, how can you move staff forward amidst restructuring? | Personnel Downsizing |
BACKGROUND: Dietitians play a vital role in the management of childhood obesity. To support that role the Obesity Specialist Group of the British Dietetic Association commissioned a review and clinical application paper. This current paper is a summary of that review document, which is available on the BDA's website. METHODS: The initial sources of evidence were guidelines, published reviews and government guidance. Best practice advice was sought from networks including the BDA's Obesity and Paediatric Specialists groups. The original document was reviewed by a review group and members of the Obesity and Paediatric Specialist group's committees. RESULTS: The overall aim of dietetic interventions in childhood weight management should be to deliver evidence based dietetic weight management care, which helps maintain positive lifestyle changes. To support this aim the review recommends the UK BMI cut off points in setting service referral and triaging criteria. Ensuring the whole child's world is taken into account when undertaking assessment and throughout the programme process is essential. Dietitians working in this field require behavioural change skills, motivational techniques and the ability to communicate to children of differing ages and their parents. Knowledge of local child safe guarding procedures are necessary for all working in this field. Recommendations on basic and advanced skills required are specified. CONCLUSIONS: This paper was written to compliment a full review document. The complexities around case management, child protection issues and competing family motivations require dietitians trained at undergraduate and postgraduate level to deliver high quality weight management and behavioural change. | Obesity Management |
A comparitive experiment was carried out with 81 calves, aged 4-15 days, to establish the effect of a tissue preparation of swine embryos after Filatov, colostral lactoplasmin, and bovine gammaglobulin as prophylactic and therapeutic means, on the sera proteins. It was found that these preparations show no influence on the protein fraction ratio. It has also been pointed out that these agents produce a strong stimulative effect on the average daily weight gain of calves up to the sixtieth day following treatment. | Organotherapy |
The nuclear receptor DAX-1, encoded by the NR0B1 gene, is presented in the hypothalamic tissues in humans and other vertebrates. Human patients with NR0B1 mutations often have hypothalamic-pituitary defects, but the involvement of NR0B1 in hypothalamic development and function is not well understood. Here, we report the disruption of the nr0b1 gene in zebrafish causes abnormal expression of gonadotropins, a reduction in fertilization rate, and an increase in postfasting food intake, which are indicators of abnormal hypothalamic functions. We find that loss of nr0b1 increases the number of prodynorphin (pdyn)-expressing neurons but decreases the number of pro-opiomelanocortin (pomcb)-expressing neurons in the zebrafish hypothalamic arcuate region (ARC). Further examination reveals that the proliferation of progenitor cells is reduced in the hypothalamus of nr0b1 mutant embryos accompanying the decreased expression of genes in the Notch signaling pathway. Additionally, the inhibition of Notch signaling in wild-type embryos increases the number of pdyn neurons, mimicking the nr0b1 mutant phenotype. In contrast, ectopic activation of Notch signaling in nr0b1 mutant embryos decreases the number of pdyn neurons. Taken together, our results suggest that nr0b1 regulates neural progenitor proliferation and maintenance to ensure normal hypothalamic neuron development. | DAX-1 Orphan Nuclear Receptor |
We used linker insertion-deletion mutagenesis to study the catalytic domain of the Harvey murine sarcoma virus v-rasH transforming protein, which is closely related to the cellular rasH protein. The mutants displayed a wide range of in vitro biological activity, from those that induced focal transformation of NIH 3T3 cells with approximately the same efficiency as the wild-type v-rasH gene to those that failed to induce any detectable morphologic changes. Correlation of transforming activity with the location of the mutations enabled us to identify three nonoverlapping segments within the catalytic domain that were dispensable for transformation and six other segments that were required for transformation. Segments that were necessary for guanosine nucleotide (GDP) binding corresponded to three of the segments that were essential for transformation; two of the three segments share strong sequence homology with other purine nucleotide-binding proteins. Loss of GDP binding was associated with apparent instability of the protein. Lesions in two of the three other required regions significantly reduced GDP binding, while small lesions in the last required region did not impair GDP binding or membrane localization. We speculate that this latter region interacts with the putative cellular target of ras. The results suggest that transforming ras proteins require membrane localization, guanosine nucleotide binding, and an additional undefined function that may represent interaction with their target. | Harvey murine sarcoma virus |
The aim of this study was to determine the changes in endurance performance and metabolic, hormonal, and inflammatory markers induced by endurance stress (marathon race) in a combined strategy of training and dietary protein supplementation. The study was designed as a randomised controlled trial consisting of regular endurance training without and with a daily intake of a soy protein-based supplement over a three-month period in 2 x 15 (10 males and 5 females per group) endurance-trained adults. Body composition (body mass, BMI, and fat mass) was determined, and physical fitness was measured by treadmill ergometry at baseline and after 3 months of intervention; changes in exercise-induced stress and inflammatory markers (CK, myoglobin, interleukin-6, cortisol, and leukocytes) were also determined before and after a marathon competition; eating behaviour was documented before and after intervention by a three-day diet diary. Although no significant influence on endurance performance was observed, the protein supplementation regime reduced the exercise-induced muscle stress response. Furthermore, a protein intake of >/=20% of total energy intake led to a lower-level stress reaction after the marathon race. In conclusion, supplementary protein intake may influence exercise-induced muscle stress reactions by changing cellular metabolism and inflammatory pathways. | Marathon Running |
Background Sporadic non-syndromic thoracic aortic aneurysms (SNSTAAs) are less well understood than familial non-syndromic or syndromic ones. Here, we focused on morphologic and molecular changes of the extracellular matrix of the tunica media of SNSTAAs. Design Single centre design. Methods Surgical media samples from seven SNSTAAs and seven controls underwent quantitative polymerase chain reaction, proteomics-bioinformatics, immunoblotting, histology and immunohistochemistry analysis. Results A down-regulation of Decorin mRNA with unchanged protein levels associated with a remarkable increase of collagen fibres. A reduced and distorted network of elastic fibres partnered with an attenuated expression of microfibril-associated glycoprotein1 despite the rise of MFAP2 gene-encoded mRNA levels. An increasingly proteolysed paxillin (55 kDa PXN), a focal adhesion protein, combined with an upregulated 62 kDa PXN holoprotein, without changes in amount and phosphorylation of focal adhesion kinase (pp125(FAK)). The upregulation of SPOCK2-encoded Testican2 proteoglycan and of ectodysplasin (EDA) protein was coupled with a down-regulation of EDA2 receptor (EDA2R). Conclusions Several tunica media extracellular matrix-related changes favour SNSTAA development. A steady level of decorin and a microfibril-associated glycoprotein1 protein shortage cause the assembly of structurally defective collagen and elastic fibres. Up-regulation of PXN holoproteins perturbs PXN/pp125(FAK) interaction and focal adhesion functioning. Testican2 up-regulation suppresses the membrane-type matrix metalloproteinase inhibiting activities of other SPOCK family members thus enhancing extracellular matrix proteolysis. Finally, the altered EDA*EDA2R signalling would impact on the remodelling of SNSTAA tunica media. Altogether, our results pave the way to a deeper molecular understanding of SNSTAAs necessary to identify their early diagnostic biochemical markers. | Xedar Receptor |
PURPOSE: We conducted a 12-month pilot study of 2 complementary strategies for improving rural cancer survivorship outcomes: (1) Project ECHO, a telementoring model to increase knowledge and skills about cancer survivorship among multidisciplinary health care provider teams in rural areas and (2) patient navigation (PN) services to connect rural cancer survivors with resources for enhancing health and wellness. METHODS: We recruited 4 CDC-funded National Comprehensive Cancer Control Program sites to implement Project ECHO and PN interventions for a defined rural population in each of their jurisdictions. Sites received ongoing technical assistance and a stipend to support implementation. We conducted a mixed-methods evaluation consisting of quantitative performance monitoring data and qualitative interviews with site staff to assess implementation. FINDINGS: Site teams delivered 21 cancer survivorship ECHO sessions to rural providers resulting in 329 participant encounters. Almost all (93%) ECHO participants reported enhanced knowledge of cancer survivorship issues, and 80% reported intent to apply learnings to their practices. Site teams engaged 16 patient navigators who navigated 164 cancer survivors during the study period. Successful implementation required strong partnerships, clear avenues for recruitment of rural providers and cancer survivors, and activities tailored to local needs. Fostering ongoing relationships among sites through community of practice calls also enhanced implementation. CONCLUSIONS: Sites successfully implemented a novel approach for enhancing care for cancer survivors in rural communities. Pairing Project ECHO to address structural barriers and PN to address individual factors affecting survivorship may help bridge the health equity gap experienced by cancer survivors in rural communities. | Patient Navigation |
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