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pubmed_882_25142 | Despite high cure rates, treatment of childhood Hodgkin Lymphoma (HL) is associated with late effects caused mainly by radiotherapy (RT). In the GPOH-HD95 trial of the German Society of Pediatric Oncology and Hematology that was recently published in the Journal of Clinical Oncology, RT was spared in patients achieving a stringently defined complete remission (CR) with chemotherapy and reduced in patients with a good partial remission (PR). Overall, RT-treated patients had superior PFS, but overall survival (OS) was almost identical within each risk-stratified treatment group irrespectively of the use of RT. In the low-risk group, RT could be safely omitted in 20% of patients. In contrast, failure rates were considered unacceptable, when RT was omitted in intermediate or high risk patients achieving a CR. However, salvage therapy was successful, equalizing overall survival between irradiated and non-irradiated patients. Although GPOH-HD95 points out to the omission of RT in selected patients achieving a CR after chemotherapy, especially those in the low-risk group, more than 80% of the patients are still irradiated. Notably, the GPOH-HD95 was not a randomized trial. In conclusion, according to the GPOH-HD95 trial, RT can be safely omitted in pediatric and adolescent patients with low-risk, early stage HL achieving a stringently defined CR after 2 cycles of OPPA or OEPA chemotherapy. RT dose could also be reduced in case of good PR by conventional imaging. However, conventional response assessment is not the optimal means to decide whether RT is needed or not. It is now increasingly recognized that RT can be omitted in many patients with HL without compromising the final outcome and it appears wise to try to stringently limit RT in those patients who really need it. This might be achieved through the use of modern functional imaging (PET/CT). Such efforts are already in progress and results regarding efficacy are awaited relatively soon. | 10.3978/j.issn.2224-4336.2013.06.03 |
pubmed_1129_22112 | BACKGROUND
Beginning readers are typically introduced to enlarged print, and the size of this print decreases as readers become more fluent. In comparison, beginning blind readers are expected to learn standard-sized Braille from the outset because past research suggests letter knowledge cannot be transferred across different sizes of Braille.
AIMS
The study aims to investigate whether learning Braille using an oversized pegboard leads to faster, transferable, letter learning and whether performance is mediated by either tactile or visual learning.
SAMPLE
Sixty-eight children participated in the study. All children were sighted pre-readers with no previous knowledge of Braille. The children came from two nursery schools with an average age of 47.8 months.
METHODS
Children were taught specific Braille letters using either an enlarged pegboard or standard Braille. Two other groups of children were taught using visually presented Braille characters in either an enlarged or standard size and a further control group mirrored the experience of blind children in receiving non-specific tactile training prior to being introduced to Braille. In all tactile conditions it was ensured that the children did not visually experience any Braille for the duration of the study.
RESULTS
Results demonstrated that initially training children with large Braille tactually led to the best subsequent learning of standard Braille. Despite the fact that both initial visual and large tactual learning were significantly faster than learning standard Braille, when transferring letter knowledge to standard tactile Braille, previous tactile experience with the large pegboard offered the most efficient route.
CONCLUSIONS
Braille letter knowledge can be transferred across size and modality particularly effectively with large tactile Braille. This has significant implications for the education of blind children. | 10.1111/bjep.12229 |
pubmed_305_19930 | Near-death experiences (NDEs) refer to profound psychological events that can have an important impact on the experiencers' (NDErs) lives. Previous studies have shown that NDEs memories are phenomenologically rich. In the present study, we therefore aimed to extract the common themes (referred to as "features" in the NDE literature) reported by NDErs by analyzing all the concepts stored in the narratives of their experiences. A qualitative thematic analysis has been carried out on 34 cardiac arrest survivors' NDE narratives. Our results shed the light on the structure of the narratives by identifying 10 "time-bounded" themes which refer to isolated events encountered during the NDE and 1 "transversal" theme which characterizes the whole narrative and generally appears as a retrospective comment of self-reflection on the experience. The division of narratives into themes provides us with detailed information about the vocabulary used by NDErs to describe their experience. This established thematic method enables a rigorous description of the phenomenon, ensuring the inclusion of all self-reported manifestations of themes in narratives. | 10.1371/journal.pone.0193001 |
pubmed_581_8063 | Molecular baskets capture various tris(2-pyridylmethyl)amine ligands, with and without zinc(II) cation, to form nesting complexes. The results of our computational (MD) and experimental (1H NMR/ITC) studies suggest that the assembly is driven by the hydrophobic effect with the charge of complementary molecular components playing an important role in the formation of nesting complexes. In brief, the complexation only takes place when the basket and the ligand carry either oppositely charged or noncharged groups. | 10.1021/acs.orglett.7b02391 |
pubmed_317_25323 | A "one-pot" tandem substitution/Krapcho reaction is reported for the facile synthesis of α-fluorinated esters and sulfones, which utilizes the byproduct salt formed in the substitution step as an indispensible reagent to facilitate the Krapcho reaction step. This represents the first sustainable tandem reaction that internally recycles the waste salt formed in the upstream step as the reagent for the downstream step. | 10.1021/acs.orglett.5b00072 |
pubmed_399_19065 | We examined the effects of atracurium and its breakdown product, laudanosine, on resting and stimulation-evoked release of 3H-noradrenaline (3H-NA) from sympathetic axon terminals of isolated right atria of guinea pigs. Both atracurium 1-100 mumol litre-1 and laudanosine 1-50 mumol litre-1 enhanced the release of 3H-NA evoked by field stimulation (2 Hz, 24 stimuli), but did not affect resting release. When the production of laudanosine from atracurium was inhibited by maintaining the atracurium solution at 4 degrees C, atracurium did not enhance the release of 3H-NA as occurred when it was kept at 37 degrees C. However, atracurium antagonized the inhibitory effect of oxotremorine on release of 3H-NA, whereas laudanosine did not. These data suggest that atracurium possesses an antimuscarinic effect. Its metabolite, laudanosine, in concentrations which would be expected following prolonged administration of atracurium, produced a marked increase in release of 3H-NA. This effect of laudanosine may explain some of the unwanted effects seen following administration of atracurium. | 10.1093/bja/62.6.683 |
pubmed_411_21139 | Springs ecosystems are globally abundant, geomorphologically diverse, and bio-culturally productive, but are highly imperiled by anthropogenic activities. More than a century of scientific discussion about the wide array of ecohydrological factors influencing springs has been informative, but has yielded little agreement on their classification. This lack of agreement has contributed to the global neglect and degradation of springs ecosystems by the public, scientific, and management communities. Here we review the historical literature on springs classification variables, concluding that site-specific source geomorphology remains the most diagnostic approach. We present a conceptual springs ecosystem model that clarifies the central role of geomorphology in springs ecosystem development, function, and typology. We present an illustrated dichotomous key to terrestrial (non-marine) springs ecosystem types and subtypes, and describe those types. We identify representative reference sites, although data limitations presently preclude selection of continentally or globally representative reference springs of each type. We tested the classification key using data from 244 randomly selected springs of 13 types that were inventoried in western North America. The dichotomous key correctly identified springs type in 87.5% of the cases, with discrepancies primarily due to differentiation of primary vs. secondary typology, and insufficient inventory team training. Using that information, we identified sources of confusion and clarified the key. Among the types that required more detailed explanation were hypocrenes, springs in which groundwater is expressed through phreatophytic vegetation. Overall, springs biodiversity and ecosystem complexity are due, in part, to the co-occurrence of multiple intra-springs microhabitats. We describe microhabitats that are commonly associated with different springs types, reporting at least 13 microhabitats, each of which can support discrete biotic assemblages. Interdisciplinary agreement on basic classification is needed to enhance scientific understanding and stewardship of springs ecosystems, the loss and degradation of which constitute a global conservation crisis. | 10.1002/eap.2218 |
pubmed_705_10863 | Anandamide is the newly discovered endogenous cannabinoid ligand that binds to brain cannabinoid receptors and shares most, but not all, of the pharmacological properties of delta 9-THC. Therefore, this study was undertaken to determine whether its interaction with the CB1 receptor in brain was identical to that of delta 9-THC. Anandamide depressed spontaneous activity and produced hypothermia, antinociception and immobility in mice after i.v. administration. However, none of these effects was blocked by pretreatment with the selective CB1 antagonist, SR 141716A. However, the metabolically stable analog 2-methyl-2'-fluoroethylanandamide produced reductions in motor activity and antinociception in mice, effects that were blocked by the antagonist. To determine whether anandamide's receptor binding mimicked that of other cannabinoids, an autoradiographic comparison of anandamide, SR 141716A and CP 55,940 competition for [3H]CP55,940 binding was conducted throughout rat brain. The receptor affinities for all three compounds did not change according to brain area. As expected, Bmax values differed dramatically among differ brain areas. However, the Bmax values for each brain area were similar regardless of the compound used for displacement. These data suggest that anandamide, SR 141716A and CP 55,940 compete for the same cannabinoid receptor throughout brain despite SR 141716A's failure to block anandamide's pharmacological effects. Although there is no question that anandamide binds to the cannabinoid receptor, failure of SR 141716A to block its pharmacological effects in mice poses a dilemma. The results presented herein raise the possibility that anandamide may not be producing all of its effects by a direct interaction with the CB1 receptor. | pubmed_705_10863 |
pubmed_1080_19173 | The benzidine congener 3,3'-dimethoxybenzidine (DMOB), and C.I. Direct Blue 15 (Blue 15), a prototypical compound of the DMOB-derived class of dyes, were evaluated in 13-week studies to characterize the toxicity and establish dose levels for subsequent chronic studies. Groups of 10 Fischer 344 rats of each sex were administered either DMOB, or Blue 15, at 1 of 5 concentrations in drinking water for 13 weeks. DMBO concentrations were 0, 0.017, 0.033, 0.063, 0.125, and 0.25% for males and females. For Blue 15, the concentrations were 0.063, 0.125, 0.25, 0.50, and 1.0% for females and 0, 0.125, 0.25, 0.50, 1.0, and 3.0% for male rats. Rats showed dose-related decreases in water consumption and weight gains. All DMOB-treated rats and their controls survived the 13-week treatment. There were 7 deaths in the 3% level of male rats treated with Blue 15. Liver and kidney weights were increased in rats treated with both compounds. Target organs for DMOB-treated rats were the kidney and thyroid. These lesions were characterized by chronic nephropathy, and increased pigment in the follicular cells of the thyroid. The kidney and liver were identified as target organs for Blue 15-treated rats. In the high-dose rats that died before termination of the study, renal effects were characterized by degeneration and focal necrosis of proximal tubular epithelial cells. Liver lesions in this group consisted of degeneration and necrosis of hepatocytes, fatty metamorphosis, and minimal megalocytosis. Mild chronic nephropathy was the principal histological effect in Blue 15-treated rats surviving to study termination. | 10.1016/0300-483x(89)90199-6 |
pubmed_740_16740 | A two-photon active probe for physiological copper (Cu2+) detection is expected to play an important role in monitoring biological metabolism. Herein, a novel Schiff base derivative (E)-2,2'-((4-((4-(diethylamino)-2-hydroxybenzylidene)amino)phenyl)azanediyl)bis(ethan-1-ol) (L) with remarkable two-photon activity was developed and synthetically investigated. L presents high selectivity and sensitivity for Cu2+ sensing in ethanol/HEPES buffer (v/v, 1 : 1), which is accompanied by the fluorescence switching "off" and subsequently "on" with the addition of EDTA. The mechanism for the detection of Cu2+ is further analyzed using 1H NMR titration, mass spectra and theoretical calculations. Furthermore, since the probe L possesses good photophysical properties, excellent biocompatibility and low cytotoxicity, it is successfully applied to track Cu2+ in the cellular endoplasmic reticulum by two-photon fluorescence imaging, showing its potential value for practical applications in biological systems. | 10.1039/c8ob00257f |
pubmed_374_4233 | BACKGROUND
One of the self-assessment tools used in shoulder instability to evaluate patient's quality of life is the Western Ontario Shoulder Instability (WOSI) Index. It is a valid and reliable disease-specific tool that has been translated into many languages. The aim of this study is to cross-culturally adapt the Western Ontario Shoulder Instability (WOSI) Index into Arabic and assess its psychometric properties in patients diagnosed with shoulder instability in order to help surgeons and physical therapists assess patients following an intervention.
PATIENTS AND METHODS
Forty-four patients with shoulder instability participated in the study. For validity and reliability, the WOSI, Disability of Arm, Shoulder and Hand questionnaire (DASH) and the American Shoulder and Elbow Surgeons (ASES) questionnaire were completed at baseline and the WOSI again within 1 week. For responsiveness the WOSI was completed 1 week postoperative and again 6 months following the completion of a rehabilitation program.
RESULTS
Cronbach's alpha (Internal Consistency) of the WOSI was 0.91 and the intraclass correlation coefficient (ICC) was 0.96 indicating high reliability. The standard error of measurement was 90.2 with the scale 0-2100 and the minimal detectable change was 250 out of 2100 (11.9%). For construct validity, there was a moderate significant correlation between the Arabic WOSI, the DASH and the ASES with r=0.60 and 0.62 respectively. The WOSI was highly responsive with an effect size of 3.17 and a standardized response mean of 2.94.
CONCLUSION
The Arabic version of the WOSI is a valid, reliable and responsive tool that can be used to assess patients with shoulder instability.
LEVEL OF EVIDENCE
I, Validity and reliability study. | 10.1016/j.otsr.2020.04.006 |
pubmed_386_12833 | The study was designed to prove the hypothesis that lipopolysaccharide (LPS)-induced fever elicits the changes in surfactant specific proteins, potentially related to thermal tachypnea. In adult rats fever was induced by intraperitoneal administration of LPS at a dose 100 microg/kg of body weight; control group received saline. Respiratory parameters, arterial blood gases and pH and colonic body temperature (BT) were recorded. Five hours later, surfactant proteins (SP) A, B, C and D were evaluated in bronchoalveolar lavage fluid (BALF) and lung tissue (LT). LPS evoked monophasic thermic response (at 300 min 38.7+/-0.2 vs. 36.4+/-0.3 °C, P 0.05) and an increase in minute ventilation due to changes in breathing rate and tidal volume. LPS-instilled animals had higher levels of SP-A and SP-D in LT (P 0.05 and 0.01), and higher SP-D in BALF (P 0.01) than controls. SP-B increased in LT and SP-C in BALF of animals with LPS (both P 0.05 vs. controls). The changes in all surfactant specific proteins are present in LPS-induced fever. Alterations of proteins related to local immune mechanisms (SP-A, SP-D) are probably a part of general inflammatory response to pyrogen. Changes in proteins related to surface activity (SP-B and SP-C) might reflect the effort of the body to stabilize the lungs in thermal challenge. | 10.33549/physiolres.932928 |
pubmed_1111_960 | Reye syndrome is a rare, but severe and often fatal disease. The etiology of the classical Reye syndrome is unknown, but it is typically preceded by a viral infection with a free interval of three to five days. The main physiopathological hypothesis is a mitochondrial metabolism insult causing acute liver failure and encephalopathy. Survivors present serious neurological sequelae. The treatment of Reye syndrome is usually medical with intensive care management. Herein, we present the clinical case of a six-month-old baby diagnosed with Reye syndrome with a fulminant hepatitis, who was successfully liver transplanted with an auxiliary partial orthotopic liver transplantation. | pubmed_1111_960 |
pubmed_958_10936 | Protein S-thiolation is a process in which under oxidative stress, vulnerable sulfhydryl groups of proteins are conjugated to non-protein thiols such as glutathione (GSH) or cysteine resulting in the formation of protein-thiol mixed disulfides, protein-S-S-glutathione (PSSG) and protein-S-S-cysteine (PSSC). This process spontaneously disrupts the redox homeostasis of the cells, which in turn leads to functional disturbances in the respective tissue. In the ocular lens, such modification of proteins may trigger a cascade of events starting with the alteration of protein conformation, protein/enzyme deactivation, protein-S-S-protein aggregation and eventually lens opacification or cataract. Generally, the first line of defense system in the cells protects the lens proteins against such damage. Recent studies in our laboratory have shown that in addition to this defense system, lens cells also possess a well developed system to repair the oxidative damage to the lens proteins. We have identified this repair system as thioltransferase (TTase) and have proved that TTase by its dethiolase activity reverses the protein S-thiolation process which returns the oxidatively damaged lens proteins/enzymes to their original reduced state and restores their physiological functions. We investigated if this repair mechanism was mediated by enzymes other than TTase. We studied glutathione S-transferase (GST) and report here for the first time the cloning, high level expression, and purification of human lens mu and pi isoforms of GST. A comparative study of recombinant human lens TTase and GST (mu and pi) on their dethiolating abilities using lens crystallin-thiol mixed disulfides showed that the lens TTase is 60-70% more efficient in the dethiolation/repair process than GST. When TTase and GST were tested in conjunction for the dethiolation of thiol mixed disulfides, there was no significant enhancement of dethiolase activity. These findings suggest that TTase by itself is an efficient enzyme in the dethiolation/repair process and hence can be considered a crucial system to counteract oxidative stress in the lens. | 10.1006/exer.1999.0659 |
pubmed_202_7311 | The authors report the case of a patient with permanent, refractory hiccup, resistant at all classical treatment methods. Hiccup was due to compression of the epigastric region by the left fist of the patient immobilised by a spastic hemiplegia. Passive mobilisation of the diseased upper limb resulted in the disappearance of hiccup. | pubmed_202_7311 |
pubmed_674_17911 | The biggest agricultural sector that contributes to the Malaysian economy is the oil palm industry. The effluent generated during the production of crude palm oil known as palm oil mill effluent (POME). POME undergoes anaerobic treatment that requires long retention time and produces large amount of methane that consequently contributes to global warming. In this study, an isolated bacteria was selected based on its ability to degrade kraft lignin (KL) and identified as Ochrobactrum sp. The bacteria were able to treat POME (from anaerobic pond) under the aerobic condition without addition of nutrient, resulting in a significant chemical oxygen demand (COD) removal of 71 %, removal rate of 1385 mg/l/day, and 12.3 times higher than that of the ponding system. It has also resulted in 60 % removal of ammoniacal nitrogen and 55 % of total polyphenolic after 6-day treatment period with the detection of lignocellulolytic enzymes. | 10.1007/s13205-016-0455-1 |
pubmed_957_13637 | OBJECTIVE
To screen differentially expressed genes (DEGs) associated with chronic schistosomiasis japonica-induced hepatic fibrosis and analyze their functions.
METHODS
The dataset of gene expression profiles of patients with chronic schistosomiasis japonica-induced hepatic fibrosis was downloaded from the Gene Expression Omnibus (GEO) database, and DEGs were screened using R package. The biological functions of DEGs were characterized using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. In addition, the protein-protein interaction (PPI) network of DEGs was created to screen the hub genes.
RESULTS
A total of 62 DEGs were identified, including 12 down-regulated genes and 50 up-regulated genes. GO enrichment analysis showed that DEGs were mainly enriched in 116 biological processes, including fatty acid, sulfur compound, acyl-coenzyme A and thioester metabolism; 19 cellular components, including mitochondrial matrix, outer mitochondrial membrane and organelle outer membrane; and 7 molecular functions, including insulin-like growth factor binding and oxidoreductase activity. KEGG pathway enrichment analysis that the DEGs were significantly enriched in phosphatidylinositol-3-kinase/serine/threonine protein kinase (PI3K/Akt), mitogen-activated protein kinase (MAPK), calcium metabolism and cyclic adenosine monophosphate (cAMP) signaling. PPI network analysis identified six hub genes involved in the development of chronic schistosomiasis japonica-induced hepatic fibrosis, including ACACA, ACSL1, GPAM, THRSP, PLIN1 and DGAT2, and ACSL1, ACACA and PLIN1 were the top 3 hub genes.
CONCLUSIONS
ACSL1, ACACA and PLIN1 may be the hub genes associated with the development of chronic schistosomiasis japonica-induced hepatic fibrosis, and abnormal lipid metabolism mediated by these DEGs may play an important role in the development of chronic schistosomiasis japonica-induced hepatic fibrosis. | 10.16250/j.32.1374.2022053 |
pubmed_773_1936 | The strain Actinoplanes garbadinensis nov. sp. produces a peptide antibiotic, named gardimycin, which is active in vitro and in vivo against Gram-positive bacteria. Isolation and purification of the product have been accomplished by extraction from the broth with butanol and dialysis of the crude extract, followed by counter-current distribution. Gardimycin is an open chain peptide with an approximate minimal formula C84H138N18S3-4O34Na. The following amino acids have been identified by column chromatography of an acid hydrolysate: serine, glutamic acid, alanine, leucine, isoleucine, glycine, valine and two sulphur-containing amino acids whose structure is presently under study. Tryptophan has been identified in an alkaline hydrolysate. | 10.7164/antibiotics.29.507 |
pubmed_911_8880 | OBJECTIVE
To better assess the diagnosis of an infection in patients presenting at an emergency department with peripheral blood leukocytosis (>10 x 10(9) cells/l) on laboratory testing.
METHODS
We prospectively evaluated serum procalcitonin concentration (PCT), C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR). Patients were divided into two groups according to their final diagnosis: patients with infection and those without infection. PCT, CRP, and ESR were compared between these groups. Sensitivity, specificity, positive predictive values, negative predictive values, receiver operating characteristic curves, and areas under the curves were calculated for each biological measurement.
RESULTS
Out of 173 patients, 99 (57%) had a final diagnosis of systemic infection. If a cutoff point of 0.5 ng/ml is considered, procalcitonin concentration had a sensitivity of 0.57, a specificity of 0.85, a negative predictive value of 0.59, and a positive predictive value of 0.84 for the diagnosis of a systemic infection. Adding CRP or ESR to PCT gave no more information (p=0.84).
CONCLUSIONS
Only about half of the patients attending the emergency department with leukocytosis were suffering from an infection. Determination of the procalcitonin level may be useful for these patients, particularly in the case of a value higher than 0.5 ng/ml. | 10.1016/j.ijid.2007.09.007 |
pubmed_391_4000 | The most striking pathological finding in the deltoid muscle biopsy specimens of 2 unrelated adult male patients consisted of large spheroid-cytoplasmic complexes of intricate structure, as previously described only under experimental conditions (Chou and Mizuno, 1986). These large cytoplasmic masses were characterized by a granular centre and a filamentous halo. Immunohistology revealed the presence of intermediate filaments of the desmin and vimentin types. Clinically, both patients showed mild and slowly progressive proximal myopathy of adult onset. In one patient, the myopathy was strongly suspected to be inherited. In concordance with previous reports on cytoplasmic and spheroid body congenital myopathies, these spheroid-cytoplasmic bodies further enlarge the spectrum of late onset congenital myopathies. | pubmed_391_4000 |
pubmed_734_9869 | BACKGROUND
Hypertensive disorders of pregnancy (HDP) are associated with dysfunctional placentation and are a major cause of maternal and neonatal morbidity and mortality. Twin pregnancies have a larger placental mass and are a risk factor for HDP. The effect of HDP on neonatal outcomes in twin pregnancies is unknown.
METHODS
Retrospective cohort study using the Canadian Neonatal Network database from 2010-2018 of twin infants <29 weeks gestation born to mothers with HDP and normotensive pregnancies. Using multivariable models, we determined adjusted odds ratios (AORs) and 95% confidence intervals (CI) for mortality, bronchopulmonary dysplasia, severe neurologic injury, severe retinopathy of prematurity (ROP), necrotizing enterocolitis, and nosocomial infection in twin infants of mothers with HDP compared to twin infants of normotensive mothers.
RESULTS
Of the 2414 eligible twin infants <29 weeks gestational age, 164 (6.8%) were born to mothers with HDP and had higher odds of severe ROP (AOR 2.48, 95% CI 1.34-4.59). Preterm twin infants born to mothers with HDP also had higher odds of mortality (AOR 2.02, 95% CI 1.23-3.32). There was no difference in other outcomes.
CONCLUSION
Preterm twin infants <29 weeks gestation of HDP mothers have higher odds of severe ROP and mortality.
IMPACT
Hypertensive disorders of pregnancy, associated with placental dysfunction, are a major cause of maternal and neonatal morbidity and mortality. Twin pregnancy, associated with a larger placental mass, is a risk factor for hypertensive disorders of pregnancy. The effect of hypertensive disorders of pregnancy on outcomes of preterm twins is unknown. Preterm twins of mothers with hypertensive disorders of pregnancy are at higher risk of severe retinopathy of prematurity and mortality. Our data can be used to counsel parents and identify infants at higher risk of severe retinopathy of prematurity and mortality. | 10.1038/s41390-022-02044-5 |
pubmed_72_20951 | UNLABELLED
HYPOTHESIS AND AIM: The large number of invalidating surgical interventions in patients suffering from lesions of the diabetic foot, the late recognition of the lesions and sometimes the wrongful interpretation of their severity, have made necessary a multi-parameter study of these types of patients and the elaboration of a therapeutic-prognostic index to guide the physician in adopting the adequate method of treatment. Starting with the therapeutic-prognostic index imagined by professor Traian Patrascu, we have elaborated a new therapeutic prognostic index, by adding new, statistically significant parameters, for the purpose of facilitating the surgical indication, depending on the lesion type.
METHODS
A number of 929 patients who were admitted at the Surgery Clinic of the "Dr. I. Cantacuzino" Hospital, between January 2013 and June 2014, have been analyzed, of whom 450 were evaluated retrospectively and 479 prospectively.
RESULTS
The new therapeutic prognostic index has been calculated for the retrospective lot, resulting into a concordance between the actual surgical intervention and the prognostic index of 79.4% and, for the patients evaluated prospectively, we have found a confirmation of the relation of 82.6% between the performed surgical intervention and the forecasted surgical intervention, by calculating the index.
DISCUSSION
The new therapeutic-prognostic index represents an easy method of establishing the therapeutic conduct of the patient suffering from lesions of the diabetic foot. It is of major use in preventing the execution of such surgical interventions that may be disproportionate compared to the severity of the lesions, especially in facilities where the pathology of the diabetic foot is less known. | pubmed_72_20951 |
pubmed_893_12937 | OBJECTIVES
To determine the frequency of medication errors and incident types in a tertiary-care hospital emergency department. To quantify and classify medication errors and identify critical points where measures should be implemented to improve patient safety.
MATERIAL AND METHODS
Prospective direct-observation study to detect errors made in June and July 2016.
RESULTS
The overall error rate was 23.7%. The most common errors were made while medications were administered (10.9%). We detected 1532 incidents: 53.6% on workdays (P=.001), 43.1% during the afternoon/evening shift (P=.004), and 43.1% in observation areas (P=.004).
CONCLUSION
The medication error rate was significant. Most errors and incidents occurred during the afternoon/evening shift and in the observation area. Most errors were related to administration of medications. | pubmed_893_12937 |
pubmed_1115_15987 | Cysteinyl leukotrienes (CysLTs) exert potent proinflammatory actions and contribute to many of the symptoms of asthma. Using a model of allergic sensitization and airway challenge with Aspergillus fumigatus (Af), we have found that Th2-type inflammation and airway hyperresponsiveness (AHR) to methacholine (MCh) were associated with increased LTD(4) responsiveness in mice. To explore the importance of increased CysLT signaling in airway smooth muscle function, we generated transgenic mice that overexpress the human CysLT1 receptor (hCysLT(1)R) via the alpha-actin promoter. These receptors were expressed abundantly and induced intracellular calcium mobilization in airway smooth muscle cells from transgenic mice. Force generation in tracheal ring preparations ex vivo and airway reactivity in vivo in response to LTD(4) were greatly amplified in hCysLT(1)R-overexpressing mice, indicating that the enhanced signaling induces coordinated functional changes of the intact airway smooth muscle. The increase of AHR imposed by overexpression of the hCysLT(1)R was greater in transgenic BALB/c mice than in transgenic B6 x SJL mice. In addition, sensitization- and challenge-induced increases in airway responsiveness were significantly greater in transgenic mice than that of nontransgenic mice compared with their respective nonsensitized controls. The amplified AHR in sensitized transgenic mice was not due to an enhanced airway inflammation and was not associated with similar enhancement in MCh responsiveness. These results indicate that a selective hCysLT(1)R-induced contractile mechanism synergizes with allergic AHR. We speculate that hCysLT(1)R signaling contributes to a hypercontractile state of the airway smooth muscle. | 10.1152/ajplung.00367.2003 |
pubmed_909_2311 | The respiration rate and the activity of some mitochondrial enzymes from pea cotyledons have been followed during the final phases of seed development, when the relative water content of the cotyledons dropped from 65 to 13%. Succinate, malate and α-ketoglutarate oxidase activity, and succinate and malate dehydrogenase activity per cotyledon increased when the relative water content dropped from 65 to about 55%. A further drop of the relative water content was accompanied by a strong decrease of the activity of the succinate and malate oxidase system, but only a slight decrease of succinate and malate dehydrogenase activity. Mitochondrial fractions from air-dry, mature cotyledons showed a low activity of the succinate and malate oxidase system but their dehydrogenase activity was relatively high. The phosphorylation efficiency and respiratory control gradually decreased during maturation. These results indicate that during maturation of the pea seed certain mitochondrial enzymes partly lose their activity. | 10.1007/BF00387505 |
pubmed_953_5942 | Arterial PCO₂ is tightly regulated via changes in breathing. A rise in PCO₂ activates the carotid bodies and exerts additional effects on neurons located within the CNS, causing an increase in lung ventilation. Central respiratory chemoreception refers to the component of this homeostatic reflex that is triggered by activation of receptors located within the brain (central chemoreceptors). Throughout the body, CO₂ generally operates via the proxy of pH. Since countless proteins, ion channels and neurons display some degree of pH-sensitivity, the notion that central respiratory chemoreception could rely on a few specialized neurons seems a priori counter-intuitive. Yet, two types of neurons currently stand out as critically important for breathing regulation by CO₂: the retrotrapezoid nucleus (RTN) and the raphe. RTN neurons are glutamatergic, strongly activated by hypercapnia in vivo and by CO₂ or protons in slices. These neurons target selectively the pontomedullary regions implicated in generating the respiratory rhythm and pattern. Their response to CO₂ seems to involve both cell-autonomous and paracrine effects of CO₂, the latter presumably mediated by the surrounding glia. The specific connections that these excitatory neurons establish with the rest of the breathing network are likely to be the main explanation of their importance to respiratory chemoreception. Serotonergic neurons have a powerful stimulatory effect on breathing, they facilitate the chemoreflexes and a subset of them likely function as CO₂ sensors. Opto- and pharmacogenetic methods have played an important role in assessing the contribution of RTN and serotonergic neurons as well as glial cells to respiration. These particular experiments are emphasized here for thematic reasons although the current perception of the importance of the RTN and serotonergic cells to respiratory chemoreception also relies on many other types of evidence. A small portion of this evidence is presented as background. This article is part of a Special Issue entitled Optogenetics (7th BRES). | pubmed_953_5942 |
pubmed_876_10356 | Androgen plays a critical role in the promotion and growth of prostate cancer. Androgen ablation has an expanding role in prostate cancer treatment and is now used to improve the efficacy of radiation therapy in addition to its role in treatment of metastatic disease. Here we show that androgen interferes with induction of prostate cancer cell death induced by a variety of stimuli. The effect of androgen on cell death occurs predominantly by interference with caspase activation and the inhibition of caspase cleavage in both the extrinsic and intrinsic cell death pathways. Androgen inhibited apoptosis induced by both tumor necrosis factor alpha (TNF-alpha) and by Fas activation with or without concomitant irradiation. An antiapoptotic effect was seen in the presence of R1881, dihydrotestosterone, and also 17beta-estradiol within 24 h of death induction. Sustained inhibition of apoptosis at 72 h was seen only with R1881, dihydrotestosterone, cyproterone acetate, and hydroxyflutamide. Androgen treatment inhibited activation of caspases-8, -7, and -9 by TNF-alpha +/- irradiation. Androgen attenuated BAX expression and blocked appearance of the proapoptotic p18 fragment of BAX. Androgen also abrogated BID cleavage induced by TNF-alpha + irradiation that contributed to a decrease in cytochrome c egress from mitochondria induced by TNF-alpha +/- irradiation. There was also decreased mitochondrial depolarization in response to TNF-alpha + irradiation. Production of the proapoptotic lipid metabolite ceramide was not affected by androgen, but androgen acted downstream from ceramide generation because R1881 blocked cell-death induction by bacterial sphingomyelinase. Inhibition of phosphoinositol-3-kinase activity by wortmannin induced apoptosis that was also blocked by androgen, but there was no effect on protein levels or phosphorylation of AKT, indicating that R1881 did not interact with survival signaling of phosphoinositol-3-kinase. Lastly, androgen inhibited activation of nuclear factor-kappaB during death induction, but the effect of androgen on cell death was not mediated by interference with the nuclear factor-kappaB pathway. The data suggest that androgen induced blockade of caspase activation in both intrinsic and extrinsic cell death pathways and thereby was able to protect prostate cancer cells from apoptosis induced by diverse stimuli. | pubmed_876_10356 |
pubmed_139_9246 | Thoracolumbar facets are not as commonly dislocated as are those of the cervical spine. It is, however, crucial to make an early and accurate diagnosis of thoracolumbar facet dislocation since the injury may be unstable and require reduction and internal fixation. This paper presents three major CT patterns of thoracolumbar facet fracture dislocation. The first represents anterior subluxation of the vertebral body with anteriorly locked facets. The second is a lateral vertebral body subluxation with laterally locked facets. The third is an acute kyphosis with little vertebral body subluxation but superiorly dislocated facets. Since the vertebral body subluxation may be missed on axial CT images, these facet-dislocation patterns should be recognized by identifying the paired superior and inferior facets and establishing their congruency. Identification of the facets is accomplished by their orientation with respect to the vertebral body (superior facets are directed posteromedially and inferior facets are directed anterolaterally) as well as by the shape of the articular surface (superior facet articular surface is concave, inferior facet articular surface is flat or convex). | 10.2214/ajr.148.2.335 |
pubmed_506_4141 | UNLABELLED
Whether preoperative clinically significant portal hypertension (CSPH) has or not an impact on the outcome of surgery for hepatocellular carcinoma (HCC) in patients with compensated cirrhosis is debated. This systematic review assesses the impact of CSPH on the outcome of HCC in patients with compensated cirrhosis treated with surgery. We performed a systematic search of the MEDLINE database (articles published in full in English language from 1996 to October 2013) and related bibliography for studies reporting on the postoperative outcomes (3- and 5-year mortality and/or early clinical decompensation) of patients with HCC and compensated cirrhosis treated with surgery according to the presence or absence of CSPH. Independent extraction of articles by two authors using predefined data fields, including study quality indicators, was used; pooled analyses were based on random-effects models. Eleven studies in total met our inclusion criteria (eight studies for 3- and 5-year postoperative mortality and eight for postoperative clinical decompensation). Moderate heterogeneity among studies for both outcomes was observed, which disappeared after pooling studies using similar methods to assess CSPH. The presence of CSPH increased the risk of 3- and 5-year mortality versus absence of CSPH (pooled odds ratio [OR] for 3-year mortality: 2.09; 95% confidence interval [CI]: 1.52-2.88; for 5-year mortality: 2.07; 95% CI: 1.51-2.84). CSPH also increased the risk of postoperative clinical decompensation (pooled OR: 3.04; 95% CI: 2.02-4.59).
CONCLUSIONS
CSPH (evaluated by any method) significantly increases the risk of 3- and 5-year mortality and of clinical decompensation after surgery for HCC. | 10.1002/hep.27431 |
pubmed_1133_21025 | Dempsey, GM, Gibson, NV, Sykes, D, Pryjmachuk, BC, and Turner, AP. Match demands of senior and junior players during International Rugby League. J Strength Cond Res 32(6): 1678-1684, 2018-This study aims to quantify and compare the positional game demands of international junior and senior rugby league competition for the first time. Global positioning system (GPS) and video analysis were used to track 118 elite male rugby league players (57 seniors aged 28.7 ± 4.4 years; 61 juniors aged 17.2 ± 0.5 years) over 10 international matches (6 senior; 4 junior) characterized as either forwards (n = 67) or backs (n = 51). There were significant increases in the offensive carries (0.18 cf. 0.09 n·min; r = 0.56) and defensive tackles (0.36 cf. 0.23 n·min; r = 0.3) between senior and junior players, and forwards and backs (0.16 cf. 0.09; r = 0.34 and 0.41 cf. 0.14; r = 0.52), respectively. Running demands were significantly greater in backs than forwards (independent of playing level) for total distance (6,962 ± 1,263 m cf. 4,879 ± 1,824 m; r = 0.55), individualized high-speed distances (310 ± 158 m cf. 250 ± 171 m; r = 0.2), high-intensity accelerations (28.7 ± 12.1 m·s cf. 21.9 ± 11.7 m·s; r = 0.27), and decelerations (57.2 ± 18.3 m·s cf. 43.0 ± 17.8 m·s; r = 0.38). Positional differences were eliminated when reported relative to minutes played. From a practical perspective, although running demands relative to time on the pitch may prepare junior players for senior competition, it is not representative of the increased body mass and contact frequency within the senior game. Coaches should therefore reflect these differences within their physical preparation programs to prepare junior athletes accordingly for progression to the senior level. | 10.1519/JSC.0000000000002028 |
pubmed_347_14315 | DNA methylation is an epigenetic mark that is essential for the development of mammals; it is frequently altered in diseases ranging from cancer to psychiatric disorders. The presence of DNA methylation attracts specialized methyl-DNA binding factors that can then recruit chromatin modifiers. These methyl-CpG binding proteins (MBPs) have key biological roles and can be classified into three structural families: methyl-CpG binding domain (MBD), zinc finger, and SET and RING finger-associated (SRA) domain. The structures of MBD and SRA proteins bound to methylated DNA have been previously determined and shown to exhibit two very different modes of methylated DNA recognition. The last piece of the puzzle has been recently revealed by the structural resolution of two different zinc finger proteins, Kaiso and ZFP57, in complex with methylated DNA. These structures show that the two methyl-CpG binding zinc finger proteins adopt differential methyl-CpG binding modes. Nonetheless, there are similarities with the MBD proteins suggesting some commonalities in methyl-CpG recognition across the various MBP domains. These fresh insights have consequences for the analysis of the many other zinc finger proteins present in the genome, and for the biology of methyl-CpG binding zinc finger proteins. | 10.4161/epi.23632 |
pubmed_769_726 | Reactive aggression is a type of aggression that has severe consequences in individual's psychosocial development and social stability. Trait anger is a risk personality factor for reactive aggression. However, the mediating mechanism of this relationship has not been sufficiently analyzed. We proposed that hostile attribution bias and anger rumination may be cognitive factors that play mediating roles in the relationship between trait anger and reactive aggression. To test this hypothesis, a sample of 600 undergraduates (51.67% females, M age = 20.51, SD = 1.11) participated in this study. Findings showed that hostile attribution bias, anger rumination sequentially mediated the association between trait anger and reactive aggression. These results highlight the importance of anger rumination and hostile attribution bias to explain the link between trait anger and reactive aggression in undergraduates. The findings of the present study also provide valuable information about the role of negative cognitive activities (e.g., hostile attribution, ruminate in anger emotion) in high trait anger individual may trigger reactive aggression. The limitations of the study are discussed, along with suggestions for future research. | 10.3389/fpsyg.2021.778695 |
pubmed_733_17523 | OBJECTIVE
To gain an insight into the relations between human leukocyte antigen-DRB1 (HLA-DRB1) alleles and idiopathic thrombocytopenic purpura (ITP) in children.
METHODS
Polymerase chain reaction-sequence specific oligonucleotide (PCR-SSO) was used to identify DRB1 alleles of 42 children with ITP. Among them, 36 were identified for anti-GPIIb/IIIa and anti-GPIb/Ix autoantibody by modified monoclonal antibody specific immobilization of platelet antigens.
RESULTS
Compared with health controls, the frequency of HLA-DRB1*17 significantly increased (P<0.05, relative risk=2.76, etiologic factor=0.1064) and the frequency of HLA-DRB1*1202 significantly decreased (P<0.025, relative risk=0.20, prophylactic factor=0.7616) in children with ITP. In comparison with patients of good response to steroids and IVIgG therapy, the frequency of HLA DRB1*11 significantly increased (Chi-square=6.091, P<0.025) in patients with a poor response, furthermore, the most of HLA-DRB1*11 positive patients were female teen-agers. Twenty-seven patients (75%) had anti GPIIb/IIIa and seventeen (47.22%) had anti_GPIb/Ix autoantibodies. The positivities of both anti_GP IIb/IIIa (P=0.02) and anti-GPIb/Ix (P=0.01) were associated with HLA-D RB1*02. However, the positivity of autoantibodies between refractory and non-refractory patients showed no significant difference.
CONCLUSION
The allele of HLA-DRB1*17 seems to predict susceptibility of ITP in children, while HLA-DRB1*1202 appears to be protective to ITP. The allele of HLA DRB1*11 plays an important role in resistance to steroid and IgG therapy in children with ITP. It seems that the response to the antigenic epitope of GPIIb/IIIa and GPIb/Ix is restricted by HLA-DRB1*02, while the presence of the antibodies could not predict prognosis. In conclusion, the above preliminary findings indicate that genetic factors influence the clinical course of ITP, but the exact mechanism needs to be investigated further. | pubmed_733_17523 |
pubmed_1045_12062 | The biologically active metabolite of vitamin D, 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) is a secosteroid whose genomic mechanism of action is similar to that of other steroid hormones and is mediated by stereospecific interaction of 1,25(OH)(2)D(3) with the vitamin D receptor (VDR) which heterodimerizes with the retinoid X receptor (RXR). After interaction with the vitamin D response element (VDRE) in the promoter of target genes, transcription proceeds through the interaction of VDR with coactivators and with the transcription machinery. The identification of the steps involved in this process has been a major focus of recent research in the field. However, the functional significance of target proteins as well as the functional significance of proteins involved in the transport and metabolism of vitamin D is also of major importance. Within the past few years much new information has been obtained from studies using knockout and transgenic mice. New insight has been obtained using this technology related to the physiological significance of the vitamin D binding protein (DBP), used to transport vitamin D metabolites, as well as the physiological significance of target proteins including 25-hydroxyvitamin D(3) 24-hydroxylase (24(OH)ase), 25-hydroxyvitamin D(3)-1 alpha-hydroxylase (1 alpha-(OH)ase), VDR, and osteopontin. The crystal structure of the DBP and the ligand binding domain of the VDR have recently been reported, explaining, in part, the unique properties of these proteins. In addition novel 1,25(OH)(2)D(3) target genes have been identified including the epithelial calcium channel, present in the proximal intestine and in the distal nephron. Thus in recent years a number of exciting discoveries have been made that have enhanced our understanding of mechanisms involved in the pleiotropic actions of 1,25(OH)(2)D(3). | 10.1002/jcb.10423 |
pubmed_675_19164 | Investigative genetic genealogy (IGG) has emerged as a new, rapidly growing field of forensic science. We describe the process whereby dense SNP data, commonly comprising more than half a million markers, are employed to infer distant relationships. By distant we refer to degrees of relatedness exceeding that of first cousins. We review how methods of relationship matching and SNP analysis on an enlarged scale are used in a forensic setting to identify a suspect in a criminal investigation or a missing person. There is currently a strong need in forensic genetics not only to understand the underlying models to infer relatedness but also to fully explore the DNA technologies and data used in IGG. This review brings together many of the topics and examines their effectiveness and operational limits, while suggesting future directions for their forensic validation. We further investigated the methods used by the major direct-to-consumer (DTC) genetic ancestry testing companies as well as submitting a questionnaire where providers of forensic genetic genealogy summarized their operation/services. Although most of the DTC market, and genetic genealogy in general, has undisclosed, proprietary algorithms we review the current knowledge where information has been discussed and published more openly. | 10.1016/j.fsigen.2021.102474 |
pubmed_804_388 | BACKGROUND
Female breast cancer incidence rates have been increasing in Portugal for years. We, therefore, conducted the first nationwide breast cancer study to assess regional differences.
METHODS
Cases were obtained from population-based cancer registries covering the country's Mainland (South, North, Centre), as well as the two Autonomous Regions (Azores and Madeira), for the time-period 1998 through 2011. Analyses were restricted to ages 30-84 years and stratified by region. We used the age-period-cohort (APC) framework to complement standard descriptive techniques and to forecast future trends. Estimable APC parameters included net drift, longitudinal age-specific incidence rate curves, and fitted age-specific incidence rate ratios.
RESULTS
There were 71 545 breast cancer cases diagnosed in Portugal at ages 30-84 years from 1998 to 2011. The South presented the highest age-standardized rate (155.8/100 000), while the North presented the fastest rate of increase (3.6%/year). Age-specific statistical interactions were observed between regions. Younger women in the North revealed a decreased risk of developing breast cancer compared to women from the same age group in the South and Centre, while that risk was reversed in older women (p < 0.05). We estimate that from 2014 onwards, the North might rank first among all regions.
CONCLUSION
The variant patterns observed could be due to a combination of different screening practices and/or exposure to risk factors across regions. Disease heterogeneity among younger and older women may also explain part of the differences in age-specific rates. These results justify continued monitoring of breast cancer incidence by region. | 10.1016/j.canep.2018.03.003 |
pubmed_396_15458 | Pacsins are cytoplasmic adapter proteins with an N-terminal FHC, a central coiled coil, and a C-terminal SH3 domain and several potential phosphorylation sites. Two murine Pacsin genes have been reported to date: Pacsin 1 (equivalent to rat Syndapin I), and Pacsin 2 (like rat Syndapin II and chicken focal adhesion protein FAP52). Rat syndapins have been well characterized as part of a synapse dynamin-associated protein complex involved in endocytosis and actin dynamics. Here we describe PACSIN 3, a third member of the pacsin gene family in humans and mice, which encodes a 424 amino acid cytoplasmic protein and has a ubiquitously expressed mRNA. Intracellular distribution was assessed by overexpression of exogenous tagged pacsin 3 protein. In addition, we report the cDNA sequence of human PACSIN 1, a gene encoding a 444 amino acid protein and its chromosome assignment to 6p21. PACSIN 1 mRNA is most abundant in brain, and is also present in heart, pancreas and liver. The close sequence conservation between the three pacsin gene products suggests they could be performing similar functions participating in the different tissues where these are expressed. | 10.1016/s0378-1119(00)00531-x |
pubmed_247_24383 | Graft pancreatitis and allograft rejection were both accompanied by increased serum levels of immunoreactive anionic trypsin (irAT) in a porcine pancreatic allograft transplantation model. Characterization of this immunoreactivity by gel filtration revealed different elution profiles in these conditions that can be helpful in the differentiation between them. During graft pancreatitis, a major part of the immunoreactivity was found within the high-molecular-weight fraction corresponding to the formation of complexes between trypsin and protease inhibitors. During allograft rejection, virtually all serum irAT increase could be attributed to the release of anionic trypsinogen without any evidence of activation. Since this transplantation model includes urinary diversion of the exocrine secretions, irAT and immunoreactive cationic trypsin (irCT) can also be measured in the urine. Characterization of this immunoreactivity showed that most of both irAT and irCT was found as active trypsin but a minor part was probably complexed with some protease inhibitor (possibly pancreatic secretory trypsin inhibitor [PSTI]). | 10.1097/00007890-199201000-00004 |
pubmed_987_1835 | Background
The ability of circulating tumor cells (CTCs) to identify lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) could improve pathological diagnosis and the selection of treatments for non-small cell lung cancer (NSCLC). Previous studies have shown that deoxyribonucleic acid (DNA) methylation exhibits cell and tissue specificity. Thus, we aimed to explore the methylation status of CTCs in LUAD and LUSC and identify the potential biomarkers.
Methods
We first analyzed Infinium 450K methylation profiles obtained from The Cancer Genome Atlas and Gene Expression Omnibus. We then performed whole-genome sequencing of CTCs in tumor and matched normal lung tissues and white blood cells from 6 NSCLC patients.
Results
The bioinformatics analysis revealed a NSCLC-specific DNA methylation marker panel, which could accurately distinguish between LUAD and LUSC with high diagnostic accuracy. The whole-genome sequencing of CTCs in NSCLC patients also showed 100% accuracy for distinguishing between LUAD and LUSC based on the CTC methylation profiles. To investigate the function of CTCs, we further analyzed similar and different methylation profiles between the CTCs and their primary tumors, and found very high similarities between the CTCs and their primary tumor tissues, indicating that these cells inherit information from primary tumors. However, the CTCs also displayed some characteristics that differed to those of primary tumor tissues, which suggest that CTCs acquire some unique characteristics after migrating from the primary tumor; these characteristics may partly explain the ability of tumor cells to evade immune surveillance.
Conclusions
Our findings provide insights into the potential use of CTCs in the pathological classification of NSCLC patients. Our findings also show how CTC primary tumor inheritance and CTC evolution affect metastasis and immune escape. | 10.21037/tlcr-22-50 |
pubmed_636_6002 | Predicting microbial survival requires reference parameters for each micro-organism of concern. When data are abundant and publicly available, a meta-analysis is a useful approach for assessment of these parameters, which can be performed with hierarchical Bayesian modeling. Geobacillus stearothermophilus is a major agent of microbial spoilage of canned foods and is therefore a persistent problem in the food industry. The thermal inactivation parameters of G. stearothermophilus (D(ref), i.e.the decimal reduction time D at the reference temperature 121.1°C and pH 7.0, z(T) and z(pH)) were estimated from a large set of 430 D values mainly collected from scientific literature. Between-study variability hypotheses on the inactivation parameters D(ref), z(T) and z(pH) were explored, using three different hierarchical Bayesian models. Parameter estimations were made using Bayesian inference and the models were compared with a graphical and a Bayesian criterion. Results show the necessity to account for random effects associated with between-study variability. Assuming variability on D(ref), z(T) and z(pH), the resulting distributions for D(ref), z(T) and z(pH) led to a mean of 3.3 min for D(ref) (95% Credible Interval CI=[0.8; 9.6]), to a mean of 9.1°C for z(T) (CI=[5.4; 13.1]) and to a mean of 4.3 pH units for z(pH) (CI=[2.9; 6.3]), in the range pH 3 to pH 7.5. Results are also given separating variability and uncertainty in these distributions, as well as adjusted parametric distributions to facilitate further use of these results in aqueous canned foods such as canned vegetables. | pubmed_636_6002 |
pubmed_1110_23420 | Microbial cell factories with the ability to maintain high productivity in the presence of weak organic acids, such as acetic acid, are required in many industrial processes. For example, fermentation media derived from lignocellulosic biomass are rich in acetic acid and other weak acids. The rate of diffusional entry of acetic acid is one parameter determining the ability of microorganisms to tolerance the acid. The present study demonstrates that the rate of acetic acid diffusion in S. cerevisiae is strongly affected by the alcohols ethanol and n-butanol. Ethanol of 40 g/L and n-butanol of 8 g/L both caused a 65% increase in the rate of acetic acid diffusion, and higher alcohol concentrations caused even greater increases. Molecular dynamics simulations of membrane dynamics in the presence of alcohols demonstrated that the partitioning of alcohols to the head group region of the lipid bilayer causes a considerable increase in the membrane area, together with reduced membrane thickness and lipid order. These changes in physiochemical membrane properties lead to an increased number of water molecules in the membrane interior, providing biophysical mechanisms for the alcohol-induced increase in acetic acid diffusion rate. n-butanol affected S. cerevisiae and the cell membrane properties at lower concentrations than ethanol, due to greater and deeper partitioning in the membrane. This study demonstrates that the rate of acetic acid diffusion can be strongly affected by compounds that partition into the cell membrane, and highlights the need for considering interaction effects between compounds in the design of microbial processes. | 10.15698/mic2018.01.609 |
pubmed_254_26276 | Several native and engineered heat-stable DNA polymerases from a variety of sources are used as powerful tools in different molecular techniques, including polymerase chain reaction, medical diagnostics, DNA sequencing, biological diversity assessments, and in vitro mutagenesis. The DNA polymerase from the extreme thermophile, Thermus scotoductus strain K1, (TsK1) was expressed in Escherichia coli, purified, and characterized. This enzyme belongs to a distinct phylogenetic clade, different from the commonly used DNA polymerase I enzymes, including those from Thermus aquaticus and Thermus thermophilus. The enzyme demonstrated an optimal temperature and pH value of 72-74°C and 9.0, respectively, and could efficiently amplify 2.5 kb DNA products. TsK1 DNA polymerase did not require additional K+ ions but it did need Mg2+ at 3-5 mM for optimal activity. It was stable for at least 1 h at 80°C, and its half-life at 88 and 95°C was 30 and 15 min, respectively. Analysis of the mutation frequency in the amplified products demonstrated that the base insertion fidelity for this enzyme was significantly better than that of Taq DNA polymerase. These results suggest that TsK1 DNA polymerase could be useful in various molecular applications, including high-temperature DNA polymerization. | 10.1002/mbo3.1149 |
pubmed_463_11051 | High abundance of c-Jun is detected in invasive breast cancer cells and aggressive breast tumor malignancies. Here, we demonstrate that a major cause of high c-Jun abundance in invasive breast cancer cells is prolonged c-Jun protein stability owing to poor poly-ubiquitination of c-Jun. Among the known c-Jun-targeting E3 ligases, we identified constitutive photomorphogenesis protein 1 (COP1) as an E3 ligase responsible for c-Jun degradation in less invasive breast cancer cells because depletion of COP1 reduced c-Jun poly-ubiquitination leading to the stabilization of c-Jun protein. In a panel of breast cancer cell lines, we observed an inverse association between the levels of COP1 and c-Jun. However, overexpressing COP1 alone was unable to decrease c-Jun level in invasive breast cancer cells, indicating that efficient c-Jun protein degradation necessitates an additional event. Indeed, we found that glycogen synthase kinase 3 (GSK3) inhibitors elevated c-Jun abundance in less invasive breast cancer cells and that GSK3β nonphosphorylable c-Jun-T239A mutant displayed greater protein stability and poorer poly-ubiquitination compared to the wild-type c-Jun. The ability of simultaneously enforced expression of COP1 and constitutively active GSK3β to decrease c-Jun abundance in invasive breast cancer cells allowed us to conclude that c-Jun is negatively regulated through the coordinated action of COP1 and GSK3β. Importantly, co-expressing COP1 and active GSK3β blocked in vitro cell growth/migration and in vivo metastasis of invasive breast cancer cells. Gene expression profiling of breast tumor specimens further revealed that higher COP1 expression correlated with better recurrence-free survival. Our study supports the notion that COP1 is a suppressor of breast cancer progression. | 10.1593/neo.13966 |
pubmed_1136_20480 | Edman degradation in the gas phase has been observed by collision activated dissociation of N-terminal phenylthiocarbamoyl (PTC) protonated peptide to yield abundant complementary b₁ and y(n-1) ion pairs. Here, we demonstrated the relation between the observed losses of aniline and/or the entire PTC derivatizing group with the availability of mobile protons using electrospray ionization mass spectrometry. In order to select the peptides with more efficient fragmentation, while simplifying the mixture of peptides, we extend the phenylisotiocyanate (PITC) derivatization of amino groups to the selective isolation of multiply charged peptides (those having the number of arginines and histidines residues higher than one) using a procedure previously developed in our group. Thus, it was possible to identify in the filtered protein database the sequence of the isolated multiply charged peptides derived from a single protein and a complex mixture of proteins extracted from Escherichia coli using only the molecular mass and the N-terminal amino acid information. For this purpose, we developed a novel bioinformatic tool for automatic identification of peptides from liquid chromatography-tandem mass spectrometry (LC-MS/MS) experiments, which potentially can be used in high-throughput proteomics. | 10.1021/ac1012738 |
pubmed_855_9126 | Twenty children (mean age 3.25 years) with congenital cyanotic heart disease undergoing modified left Blalock-Taussig (BT) shunt were studied. The mean follow-up period was 9.5 months (range 6 months to 1 year). The shunt was performed for cyanotic spells in 15 (75%) and hypoplastic pulmonary arteries in 5 (25%) patients. There were no immediate or late complications. None had cyanotic spell after the shunt. The mean arterial oxygen saturation improved from 66.47 +/- 11.9 to 76.97 +/- 8.16% (p = 0.0003) and mean hematocrit decreased from 51.55 +/- 9.5 to 46.5 +/- 9.7 (p = 0.002) after the shunt. The left atrial systolic volume and left ventricular diastolic volume also increased significantly following the shunt (from 15.82 +/- 6.37 to 20.83 +/- 8.91 ml p = 0.006 and from 36.13 +/- 16.08 to 41.08 +/- 20.07 ml (p = 0.01) respectively. There was significant growth of main, right and left pulmonary arteries and pulmonary valve annulus after the procedure. | pubmed_855_9126 |
pubmed_976_14965 | UNLABELLED
The goal of this study was to determine whether the preoperative diagnosis of obstructive sleep apnea (OSA) is an independent risk factor for perioperative complications in patients undergoing nonotorhinolaryngologic outpatient surgical procedures. We used existing databases to identify 234 patients with polysomnography-confirmed OSA who had outpatient surgical procedures in the years 1997 through 2000. Control patients were matched for type of anesthesia, age, sex, body mass index, surgical procedure, and surgical date. Their perioperative medical records were reviewed. There was no significant difference in the intraoperative management of OSA and control patients, except that the laryngeal mask airway was less likely to be used in OSA patients. There was no significant difference in the rate of unplanned hospital admissions (23.9% versus 18.8%; odds ratio, 1.4; 95% confidence interval, 0.8-2.5) or other adverse events (2.1% versus 1.3%; odds ratio, 1.7; 95% confidence interval, 0.4-7.0) between OSA and non-OSA patients. Further, when admission did occur, it was generally unrelated to cardiac or respiratory events. In this retrospective analysis, the preoperative diagnosis of OSA was not a risk factor for either unanticipated hospital admission or for other adverse events among patients undergoing outpatient surgical procedures in a tertiary referral center.
IMPLICATIONS
In patients scheduled for outpatient surgery in a large academic practice, the diagnosis of obstructive sleep apnea confirmed by polysomnography was not an independent risk factor for unanticipated hospital admission or for other adverse perioperative events. | 10.1213/01.ANE.0000061585.09157.66 |
pubmed_3_24634 | The US Department of Defense requested that the Advisory Committee on Immunization Practices-Armed Forces Epidemiological Board joint Smallpox Vaccine Safety Working Group define the likelihood that smallpox vaccination played a causal role in the fatal illness of an Army reservist. Reported serious adverse events for which there was no a priori reason to discount the existence of a causal association with smallpox vaccine were reviewed to assess whether they were signals of constellations of vaccine-associated adverse events. A causal relationship between the immunization experience and the index patient's death was favored, but the implication of an individual vaccine was precluded. No new smallpox vaccine-associated clinical syndromes were identified. The data supported neutrality regarding the hypothesis that dilated cardiomyopathy was causally associated with smallpox vaccine-induced myocarditis. This review of sentinel cases augmented the ongoing safety review process and was transparent, but it shares limitations with other case-based causality-assessment methods. | 10.1086/524750 |
pubmed_504_12970 | The source flaw associated with the basis vector in the reference-frame-independent measurement-device-independent quantum key distribution (RFI-MDI-QKD) has not been systematically studied. As a result, it is often assumed that bit error is equal to phase error, which is not theoretically rigorous. Here, we propose a postprocessing method to estimate the phase error rate from the discarded mismatched-basis statistics, where the qubit source does not need to be characterized in detail. The source flaw in the basis vector of the RFI-MDI-QKD protocol can thus be corrected using this method. The numerical simulation results clearly demonstrate that the RFI-MDI-QKD protocol with uncharacterized sources is also insensitive to the misalignment of the reference frame. | 10.1364/OL.403481 |
pubmed_1047_13045 | 42 distal radius fractures have been submitted to further examination after percutaneous intramedullary pin fixation. The outcome were 95.3% of very good to good anatomic results and 90.5% of satisfying functional results. This showed the close link between the radiological-anatomical and functional results. The success of the treatment was very acceptable, although the Morbus Sudeck as the major complication--with 7.2%--was still relatively frequently observed. It could be seen that particularly fractures at the risk of dislocation with smash zone constituted an indication for the percutaneous intramedullary pin fixation, that is to say all fractures for which a retention is primarily difficult. It constitutes a supplement, as well as an extension to the therapy of the distal radius fractures. | 10.1055/s-2008-1039831 |
pubmed_15_18795 | Grafted SMA containing poly(styrene-co-maleic anhydride)-g-(poly(ethylene glycol) monomethyl ether) (SMA-PEG) and its hydrophobically modified products poly(styrene-co-maleic anhydride)-g-(poly(ethylene glycol) monomethyl ether & dodecyl) (SMA-PEG+C(12)) and poly(styrene-co-maleic anhydride)-g-(dodecyl) (SMA-C(12)) were prepared using a single batch method. Their adsorption and rheology behavior was investigated using equilibrium surface tension and rheological techniques. The adsorption parameters, saturation surface excess concentration (Γ(max)), and the minimum area (A(min)) of these copolymers were evaluated. The results show that Γ(max) increased and A(min) correspondingly decreased with increasing hydrophobicity. Aggregation standard free energy of SMA-PEG+C(12) and SMA-C(12) suggested that increased hydrophobicity enhanced the tendency for aggregation to occur. The distinctive differences in the macroscopic appearance were shown by aqueous samples of the copolymers. The samples of SMA-M behaved as Newtonian fluids at all concentrations (from 1.0 wt% to 20.0 wt%), indicating that there were no macromolecular chain entanglements or interactions between aggregates in solution. For SMA-PEG+C(12), at concentrations above 10.0 wt%, the presence of cross-links between aggregates is presumed to be the reason for the viscoelastic behavior. Solid-like elastic behavior could occur at low concentration (5.0 wt%) of SMA-C(12), suggesting the formation of networks by inter-chain aggregation of the hydrophobic dodecyl chains. | 10.1016/j.jcis.2012.01.052 |
pubmed_405_9827 | BACKGROUND
Somatoform disorders are characterised by chronic, medically unexplained physical symptoms (MUPS). Although different medications are part of treatment routines for people with somatoform disorders in clinics and private practices, there exists no systematic review or meta-analysis on the efficacy and tolerability of these medications. We aimed to synthesise to improve optimal treatment decisions.
OBJECTIVES
To assess the effects of pharmacological interventions for somatoform disorders (specifically somatisation disorder, undifferentiated somatoform disorder, somatoform autonomic dysfunction, and pain disorder) in adults.
SEARCH METHODS
We searched the Cochrane Depression, Anxiety and Neurosis Review Group's Specialised Register (CCDANCTR) (to 17 January 2014). This register includes relevant randomised controlled trials (RCTs) from The Cochrane Library (all years), MEDLINE (1950 to date), EMBASE (1974 to date), and PsycINFO (1967 to date). To identify ongoing trials, we searched ClinicalTrials.gov, Current Controlled Trials metaRegister, the World Health Organization International Clinical Trials Registry Platform, and the Chinese Clinical Trials Registry. For grey literature, we searched ProQuest Dissertation & Theses Database, OpenGrey, and BIOSIS Previews. We handsearched conference proceedings and reference lists of potentially relevant papers and systematic reviews and contacted experts in the field.
SELECTION CRITERIA
We selected RCTs or cluster RCTs of pharmacological interventions versus placebo, treatment as usual, another medication, or a combination of different medications for somatoform disorders in adults. We included people fulfilling standardised diagnostic criteria for somatisation disorder, undifferentiated somatoform disorder, somatoform autonomic dysfunction, or somatoform pain disorder.
DATA COLLECTION AND ANALYSIS
One review author and one research assistant independently extracted data and assessed risk of bias. Primary outcomes included the severity of MUPS on a continuous measure, and acceptability of treatment.
MAIN RESULTS
We included 26 RCTs (33 reports), with 2159 participants, in the review. They examined the efficacy of different types of antidepressants, the combination of an antidepressant and an antipsychotic, antipsychotics alone, or natural products (NPs). The duration of the studies ranged between two and 12 weeks.One meta-analysis of placebo-controlled studies showed no clear evidence of a significant difference between tricyclic antidepressants (TCAs) and placebo for the outcome severity of MUPS (SMD -0.13; 95% CI -0.39 to 0.13; 2 studies, 239 participants; I(2) = 2%; low-quality evidence). For new-generation antidepressants (NGAs), there was very low-quality evidence showing they were effective in reducing the severity of MUPS (SMD -0.91; 95% CI -1.36 to -0.46; 3 studies, 243 participants; I(2) = 63%). For NPs there was low-quality evidence that they were effective in reducing the severity of MUPS (SMD -0.74; 95% CI -0.97 to -0.51; 2 studies, 322 participants; I(2) = 0%).One meta-analysis showed no clear evidence of a difference between TCAs and NGAs for severity of MUPS (SMD -0.16; 95% CI -0.55 to 0.23; 3 studies, 177 participants; I(2) = 42%; low-quality evidence). There was also no difference between NGAs and other NGAs for severity of MUPS (SMD -0.16; 95% CI -0.45 to 0.14; 4 studies, 182 participants; I(2) = 0%).Finally, one meta-analysis comparing selective serotonin reuptake inhibitors (SSRIs) with a combination of SSRIs and antipsychotics showed low-quality evidence in favour of combined treatment for severity of MUPS (SMD 0.77; 95% CI 0.32 to 1.22; 2 studies, 107 participants; I(2) = 23%).Differences regarding the acceptability of the treatment (rate of all-cause drop-outs) were neither found between NGAs and placebo (RR 1.01, 95% CI 0.64 to 1.61; 2 studies, 163 participants; I(2) = 0%; low-quality evidence) or NPs and placebo (RR 0.85, 95% CI 0.40 to 1.78; 3 studies, 506 participants; I(2) = 0%; low-quality evidence); nor between TCAs and other medication (RR 1.48, 95% CI 0.59 to 3.72; 8 studies, 556 participants; I(2) =14%; low-quality evidence); nor between antidepressants and the combination of an antidepressant and an antipsychotic (RR 0.80, 95% CI 0.25 to 2.52; 2 studies, 118 participants; I(2) = 0%; low-quality evidence). Percental attrition rates due to adverse effects were high in all antidepressant treatments (0% to 32%), but low for NPs (0% to 1.7%).The risk of bias was high in many domains across studies. Seventeen trials (65.4%) gave no information about random sequence generation and only two (7.7%) provided information about allocation concealment. Eighteen studies (69.2%) revealed a high or unclear risk in blinding participants and study personnel; 23 studies had high risk of bias relating to blinding assessors. For the comparison NGA versus placebo, there was relatively high imprecision and heterogeneity due to one outlier study. Although we identified 26 studies, each comparison only contained a few studies and small numbers of participants so the results were imprecise.
AUTHORS' CONCLUSIONS
The current review found very low-quality evidence for NGAs and low-quality evidence for NPs being effective in treating somatoform symptoms in adults when compared with placebo. There was some evidence that different classes of antidepressants did not differ in efficacy; however, this was limited and of low to very low quality. These results had serious shortcomings such as the high risk of bias, strong heterogeneity in the data, and small sample sizes. Furthermore, the significant effects of antidepressant treatment have to be balanced against the relatively high rates of adverse effects. Adverse effects produced by medication can have amplifying effects on symptom perceptions, particularly in people focusing on somatic symptoms without medical causes. We can only draw conclusions about short-term efficacy of the pharmacological interventions because no trial included follow-up assessments. For each of the comparisons where there were available data on acceptability rates (NGAs versus placebo, NPs versus placebo, TCAs versus other medication, and antidepressants versus a combination of an antidepressant and an antipsychotic), no clear differences between the intervention and comparator were found.Future high-quality research should be carried out to determine the effectiveness of medications other than antidepressants, to compare antidepressants more thoroughly, and to follow-up participants over longer periods (the longest follow up was just 12 weeks). Another idea for future research would be to include other outcomes such as functional impairment or dysfunctional behaviours and cognitions as well as the classical outcomes such as symptom severity, depression, or anxiety. | 10.1002/14651858.CD010628.pub2 |
pubmed_1007_9466 | B10.S mice have been considered resistant to experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis. However, sensitization with a myelin oligodendrocyte glycoprotein (MOG) peptide, MOG(92-106), induced clinical signs in 30% of mice and central nervous system (CNS) pathology in 93% of mice. Symptomatic mice had more demyelination, inflammation, perivascular cuffing and axonal damage in the CNS compared to asymptomatic mice, but no strong correlations between CNS pathology and clinical score were found. Interestingly, the ratio of B cells to T cells in cellular infiltrates correlated with clinical score. This suggests that the balance between B and T cells contributes to expression of clinical signs. | 10.1016/j.yexmp.2008.03.005 |
pubmed_335_16676 | Learning ability is a vitally important, distinctive property of biological systems, which provides dynamic stability in non-stationary environments. Although several different types of learning have been successfully modeled using a universal computer, in general, learning cannot be described by an algorithm. In other words, algorithmic approach to describing the functioning of biological systems is not sufficient for adequate grasping of what is life. Since biosystems are parts of the physical world, one might hope that adding some physical mechanisms and principles to the concept of algorithm could provide extra possibilities for describing learning in its full generality. However, a straightforward approach to that through the so-called physical hypercomputation so far has not been successful. Here an alternative approach is proposed. Biosystems are described as achieving enumeration of possible physical compositions though random incremental modifications inflicted on them by active operating resources (AORs) in the environment. Biosystems learn through algorithmic regulation of the intensity of the above modifications according to a specific optimality criterion. From the perspective of external observers, biosystems move in the space of different algorithms driven by random modifications imposed by the environmental AORs. A particular algorithm is only a snapshot of that motion, while the motion itself is essentially trans-algorithmic. In this conceptual framework, death of unfit members of a population, for example, is viewed as a trans-algorithmic modification made in the population as a biosystem by environmental AORs. Numerous examples of AOR utilization in biosystems of different complexity, from viruses to multicellular organisms, are provided. | 10.1007/s00422-018-0757-y |
pubmed_1007_17308 | The immuno therapeutic potential of hydro-methanolic extract of Azadirachta indica (A. indica) was studied during bovine clinical mastitis (CM). The somatic cell count (SCC), total bacterial count (TBC), milk differential leukocyte count (DLC), hydrogen peroxide (H(2)O(2)), superoxide anion (O(2) (-)) production and interleukin- 2 (IL-2) and gamma interferon (IFN-gamma) cytokines expression were studied before and after intramammary infusion of A. indica extract in diseased cows. The results revealed that A. indica treatment significantly (P < 0.05) decreased the SCC, TBC, milk neutrophil percent and significantly (P < 0.05) enhanced milk lymphocyte percent, H(2)O(2) and O(2) (-) production by milk cells. The IL-2 and IFN-gamma were expressed in normal healthy cows and diseased cows after A. indica treatment, whereas both the cytokines could not be expressed in cows treated with antibiotic and in untreated diseased cows. The results of the present study indicated anti inflammatory, antibacterial and immunomodulatory potential of the herb, these activities could be due to the presence of bioactive principle in the extract. This is a preliminary trial indicated beneficial effect of the herb against bovine mastitis it can be developed as an alternative therapy where the use of antibiotics is normally restricted. | 10.1007/s11250-008-9174-x |
pubmed_868_3786 | The lamina cribrosa likely plays an important role in retinal ganglion cell axon injury in glaucoma. We sought to (1) better understand optic nerve head (ONH) structure and anterior lamina cribrosa surface (ALCS) microarchitecture between fellow eyes of living, normal non-human primates and (2) characterize the time-course of in vivo structural changes in the ONH, ALCS microarchitecture, and retinal nerve fiber layer thickness (RNFLT) in non-human primate eyes with early experimental glaucoma (EG). Spectral domain optical coherence tomography (SDOCT) images of the ONH were acquired cross-sectionally in six bilaterally normal rhesus monkeys, and before and approximately every two weeks after inducing unilateral EG in seven rhesus monkeys. ONH parameters and RNFLT were quantified from segmented SDOCT images. Mean ALCS pore area, elongation and nearest neighbor distance (NND) were quantified globally, in sectors and regionally from adaptive optics scanning laser ophthalmoscope images. In bilaterally normal monkeys, ONH parameters were similar between fellow eyes with few inter-eye differences in ALCS pore parameters. In EG monkeys, an increase in mean ALCS Depth (ALCSD) was the first structural change measured in 6 of 7 EG eyes. A decrease in mean minimum rim width (MRW) simultaneously accompanied this early change in 4 of 6 EG eyes and was the first structural change in the 7th EG eye. Mean ALCS pore parameters were among the first or second changes measured in 4 EG eyes. Mean ALCS pore area and NND increased in superotemporal and temporal sectors and in central and peripheral regions at the first time-point of change in ALCS pore geometry. RNFLT and/or mean ALCS radius of curvature were typically the last parameters to initially change. Survival analyses found mean ALCSD was the only parameter to significantly show an initial change prior to the first measured loss in RNFLT across EG eyes. | 10.1371/journal.pone.0134223 |
pubmed_648_9517 | Recently varieties of Bodipy derivatives showing intersystem crossing (ISC) have been reported as triplet photosensitizers, and the application of these compounds in photocatalysis, photodynamic therapy (PDT), and photon upconversion are promising. In this review we summarized the recent development in the area of Bodipy-derived triplet photosensitizers and discussed the molecular structural factors that enhance the ISC ability. The compounds are introduced based on their ISC mechanisms, which include the heavy atom effect, exciton coupling, charge recombination (CR)-induced ISC, using a spin converter and radical enhanced ISC. Some transition metal complexes containing Bodipy chromophores are also discussed. The applications of these new triplet photosensitizers in photodynamic therapy, photocatalysis, and photon upconversion are briefly commented on. We believe the study of new triplet photosensitizers and the application of these novel materials in the abovementioned areas will be blooming. | 10.3389/fchem.2019.00821 |
pubmed_222_1574 | BACKGROUND
Increased levels of carboxyhemoglobin (COHb) in smokers are blamed for inducing pre-hypoxic tendency classified as anemic hypoxia. If COHb can be simply converted to altitude, there should be significant differences between smokers and nonsmokers with respect to hypoxia tolerance. However, the studies of the effects of carbon monoxide and/or smoking habit on the physiological functions at altitude do not have consistent conclusions, and many pilots still have smoking habits. This study was designed to assess whether there is a definite significant difference for time of useful consciousness (TUC), subjective symptoms, or performance degradation between nonsmokers and smokers.
METHODS
During the hypoxia experience of routine physiological training, TUC and 12 typical subjective symptoms were examined at the chamber altitude of 25,000 ft (7620 m) in 589 nonsmokers and 582 smokers in Study 1. The time until the deterioration of handwriting was assessed by 6 physiological training observers in 51 nonsmokers and 70 smokers in Study 2. The results were compared between the groups.
RESULTS
Smokers revealed significantly fewer subjective symptoms in 5 out of 12 symptoms. There were no significant differences in TUC and the rate of handwriting deterioration between the groups.
CONCLUSIONS
Paradoxically, smokers are slightly resistant to hypoxia with respect to emerging subjective symptoms. However, bluntness to hypoxia could postpone the detection of the possible hypoxic occurrence in pilots. | pubmed_222_1574 |
pubmed_533_11022 | In patients with suspected or established hypertrophic cardiomyopathy (HCM), cardiovascular magnetic resonance (CMR) is widely employed for clinical management, given its multimodality approach capable of providing unique information on cardiac morphology, function, and tissue characterization. Guidance regarding all aspects of HCM diagnosis and management is provided by the comprehensive 2014 European Society of Cardiology (ESC) guidelines on HCM. CMR should be performed in centres with recognized expertise in heart muscle diseases, by physicians who are familiar with the whole HCM disease spectrum, differential diagnoses, and pitfalls. Because CMR is usually performed and interpreted by physicians not directly involved in patient care, detailed, bidirectional, and standardized communication becomes essential to obtain best results and avoid misinterpretation. In order to maximize the potential of CMR, it is of paramount importance that reporting physicians are provided with the essential clinical information and that, in turn, referring physicians are given a core set of CMR morphological, functional, and tissue characterization results following the test. This article aims to summarize the current knowledge on the role of CMR in managing HCM and, in addition, to review the importance of the clinical context in which the report is provided, in both adult and paediatric population, highlighting implications for clinical research. | 10.1093/ehjci/jex323 |
pubmed_1121_9108 | The discovery of enzyme targeting inhibitors is a popular area of drug research. Biological activities of the compounds bearing phenol and heteroaryl groups make them popular groups in drug design targeting important enzymes such as acetylcholinesterase (AChE, E.C.3.1.1.7) and carbonic anhydrases (CAs, EC 4.2.1.1). 1-(4-hydroxyphenyl)- 2-((aryl)thio)ethanones as possible AChE and CAs inhibitors were synthesized, and their chemical structures were confirmed by IR, 1H NMR, 13C NMR, and HRMS. The compounds 2 and 4 were found potent AChE inhibitors with the Ki values of 22.13 ±1.96 nM and 23.71 ±2.95 nM, respectively, while the compounds 2 (Ki = 8.61 ±0.90 nM, on hCA I) and 1 (Ki = 8.76 ±0.84 nM, on hCA II) had considerable CAs inhibitory potency. The lead compounds may help the scientists for the rational designing of an innovative class of drug candidates targeting enzyme-based diseases. | 10.3906/kim-2004-36 |
pubmed_744_150 | Recent data have demonstrated that fast-cleaving embryos produced in vitro are more likely to develop to blastocyst stage, and that the postfertilization culture system used impacts considerably on the mRNA expression and quality of blastocysts produced. The present study is the first to investigate the relationship between the developmental speed of embryos produced in vivo or in vitro and the temporal transcription pattern. Genes related to important preimplantation events are monitored during the first 4 days of embryo development in embryos with fast or slow development. The set of genes analyzed in the present study characterizes several important physiological processes including: transport and metabolism of fructose (Glut-5), stress (SOX), mitochondrial activity and detoxification of reactive oxygen species (MnSOD), cell communication (Cx43), maternal recognition of pregnancy (IFN-tau), imprinting (IGF-II), apoptosis (Bax), growth factor binding and metabolism (IGF-IR), and oxidative stress (G6PD). Using real time PCR, we have found that for all the genes analyzed there are differences in mRNA expression between embryos with fast and slow developmental speed produced both in vitro and in vivo. Frequently, genes that may be stress induced such as SOX, MnSOD, BAX, IFtau, and G6PD were highly transcribed in in vitro produced embryos and in embryos with slow developmental speed. On the other side, transcripts from genes related with metabolism, growth, and differentiation (Glut-5, Cx 43, IGF-II, and IGF-IR) were detected in higher amounts in in vivo produced embryos and in embryos with fast developmental speed. Moreover, it is interesting to stand out that for some genetic markers (such as SOX and G6PD) there are in vivo and in vitro differences that can be observed even before materno-zygotic transition, which probably reflects a differential mRNA degradation. These transcription patterns reflects the embryonic response to the adverse in vitro culture conditions, and connect the low quality of embryos which slow developmental speed produced in vivo and in vitro, with the mRNA expression pattern of some embryonic genes. | 10.1002/mrd.20113 |
pubmed_958_11573 | PURPOSE
The effect of midazolam on intraocular pressure (IOP) in adults was studied as an initial step in determining whether it can be used as a preoperative anxiolytic or sedative agent in children with glaucoma who are undergoing examination for IOP measurements.
METHODS
This study followed a prospective, placebo controlled, randomized, double masked design. Fifty-five participants were enrolled after informed consent was obtained. Each enrolled patient underwent a brief history and eye examination. Measurements of IOP were taken at baseline and 5, 10, and 15 minutes after intravenous administration of 1 mg midazolam or placebo. IOP was the primary outcome measured.
RESULTS
There was no difference in IOP fluctuation from baseline between patients who received midazolam and those who received placebo.
CONCLUSION
Early results indicate that because midazolam does not lower IOP, it may be a useful adjunct to ketamine anesthesia in children with glaucoma undergoing ophthalmologic examination under anesthesia. However, studies of midazolam must be conducted in children and patients with glaucoma before its use in these populations can be recommended. | pubmed_958_11573 |
pubmed_711_14906 | 125I-labelled gastric inhibitory polypeptide (125I-GIP) is directly cross-linked to its specific receptor in hamster pancreatic beta cell membranes by using an ultraviolet irradiation procedure. This approach results in the identification of a GIP-protein complex of apparent Mr 64,000. The labelling of this protein species is specific since it is inhibited when incubating the membranes with increasing doses of native GIP (0.1 nM-1 microM) together with 125I-GIP, half-maximal inhibition being elicited by 5 nM peptide. Reduction of the GIP-protein complex by 100 mM dithiothreitol induces a decrease of the electrophoretic mobility of the complex. Alternatively pretreatment of membranes with dithiothreitol (up to 1 M) does not prevent the binding of 125I-GIP to its receptor. When prelabelled membranes are extracted by 0.5% Triton X-100 (v/v) and the extract is layered on a Sephadex G-50 column, a high peak of radioactivity is eluted with the void volume of the column. Treatment of this peak by 10 min ultraviolet irradiation followed by SDS-PAGE leads to identification of a major band of Mr 64,000. When the peak is further layered on Sephacryl S-200 it yields a single peak of radioactivity corresponding to a protein species with a Stokes radius of 3.2 nm and an apparent Mr of 65,000. The solubilized GIP-receptor complex is specifically adsorbed by Sepharose coupled to wheat germ agglutinin and concanavalin A and eluted from these lectins by their respective sugars. In conclusion the GIP receptor in pancreatic beta cells is a protein monomer of apparent Mr 59 000; its structure is maintained by intrachain disulfide bridges, these bonds being, however, not involved in the interaction of GIP with its receptor; the GIP receptor is a glycoprotein containing N-acetylglucosamine, mannose and probably sialic acid in its carbohydrate moiety. | 10.1111/j.1432-1033.1986.tb09875.x |
pubmed_1093_16306 | The anomalous mole fraction effect (AMFE) is an important indicator of ion-ion interactions in the pore of voltage-gated Ca2+ channels (VGCCs). The residues at position 1144 that differ in several classes of VGCCs are important to the permeation of the pore. Phe-1144 (F, CaV1) was substituted with glycine (G, CaV2) and lysine (K, CaV3) and the effects of mutation on the voltage and concentration dependency of AMFE were observed. Whole-cell currents were recorded in external solutions with Ca2+ and Ba2+ at the indicated ratios with a total divalent cation concentration of 2, 10 or 20 mM, at holding potentials from -80 to -20 mV. Results showed the ratio of Ba2+ to Ca2+ currents determined at 2 mM to be different from that determined under higher concentrations for wild-type channels but this ratio was not different when tail currents were evoked at different potentials. AMFE was greatest at relatively positive potentials (-20 mV) and when the total divalent cation concentrations were kept low (2 mM). AMFE was attenuated for F/G while it was accentuated for F/K compared with wild-type, respectively. The results demonstrated that glycine and lysine substitutions of Phe-1144 affect AMFE through different mechanisms. Additionally, residues at position 1144 were shown to be major determinates of channel permeation of several classes of VGCCs. | 10.3892/mmr.2012.1210 |
pubmed_1128_10209 | Endurance training by swimming (219-229 h) resulted in a significant protection against hypoxia/reoxygenation-induced injuries in Langendorff-perfused rat hearts. The protection was manifested as improved flow characteristics and a smaller release of creatine kinase into the perfusate. The concentration of thiobarbituric acid reactive substances (TBARS) was lower in the trained than in the respective control hearts. The trained hearts also showed a lower reoxygenation-induced increase in TBARS. The myocardium of the right ventricle and that of the left subepimyocardium were the most affected by reoxygenation. The swimming program induced a decrease in the activities of catalase and glutathione reductase in all parts of the myocardium measured. A decrease in vitamin E concentration in the subendomyocardium of the left ventricle and an increase in the activity of thioredoxin reductase also occurred. An increase in the concentration of reduced glutathione due to training was also observed, especially in the left subepimyocardium, whereas the glutathione disulfide concentration and the activity of superoxide dismutase were unaffected. The activity of glucose 6-phosphate dehydrogenase increased in the right ventricle. The results suggest both the importance of cellular redox state and the role of a lower degree of enzymatic antioxidants in training-induced protection against ischemic injuries. | 10.1152/jappl.1990.68.4.1672 |
pubmed_633_9110 | We have investigated the structures, stabilities, aromaticities, and Wiberg bond indices of four types of compounds (8-like, trapezia, umbrella-like, and quadrangle) containing planar tetracoordinate carbon (ptC), and the stability rules for the compound with ptC were concluded on the basis of extensive calculations. Generally, the stability or viability of compound with ptC strongly depends on the number of three-membered ring and conjugated three-membered ring, as well as pi electrons. These rules can be successfully used to identify the stability of other compounds reported in previous studies. On the basis of these rules, eight stable compounds with planar tetracoordinate nitrogen (ptN) are successfully constructed. | 10.1021/jp102678v |
pubmed_164_14295 | BACKGROUND
The role of inflammasomes in chronic inflammation has been the subject of intense research in recent years. Chronic rhinosinusitis (CRS), a persistent inflammatory disease, continues to be investigated hoping that a clearer pathophysiologic description will guide discovery of future treatment modalities. This study investigates the role of inflammasome complexes in CRS patients with Staphylococcus aureus biofilm infection, a key culprit associated with disease severity and recalcitrance.
METHODOLOGY
Sinonasal tissue samples were collected from CRS patients with (P+) and without (P-) polyps and controls. S. aureus biofilm status was obtained using fluorescence in situ hybridization and classified as biofilm positive (B+) or negative (B-). RNA was analysed using a Human Inflammasome PCR array, profiling the expression of 84 genes involved in inflammasome function.
RESULTS
Sixteen samples were obtained: 5 B+P+, 5 B-P- and 6 controls. Comparing B+P+ vs. controls showed the greatest number of differentially expressed genes. In particular, Absent in Melanoma 2 (AIM2) was consistently and significantly up-regulated in the B+P+ vs. B-P- and controls. In contrast, when comparing the B-P- vs. controls, no genes showed significant changes.
CONCLUSION
Our results indicate the involvement of inflammasome complexes and their signalling pathways in CRS patients with polyps and S. aureus biofilms. In particular, AIM2, activated by intracellular double-stranded DNA, is up-regulated in this group, implying that S. aureus may play a role in intracellular triggering of the inflammasome response. Studies with further patient stratification and assessing corresponding protein expression are needed to further characterize the role of inflammasomes in CRS. | 10.4193/Rhino13.045 |
pubmed_228_17535 | We calculate the electric-dipole and magnetic-quadrupole form factors of the deuteron that arise as a low-energy manifestation of parity and time-reversal violation in quark-gluon interactions. We consider the QCD vacuum angle and the dimension-six operators that originate from physics beyond the standard model: the quark electric and chromoelectric dipole moments and the gluon chromoelectric dipole moment. Within the framework of two-flavor chiral perturbation theory, we show that in combination with the nucleon electric dipole moment, the deuteron moments would allow an identification of the dominant source(s) of symmetry violation. | 10.1103/PhysRevLett.107.091804 |
pubmed_159_4995 | BACKGROUND
Prophylactic vaccines are critical in preventing hand, foot, and mouth disease (HFMD) primarily caused by human enterovirus 71 (EV71) infection. Children aged less than 5 years are especially susceptible to EV71 infections. In addition to the development of vaccines containing the inactivated virus, those containing virus-like particles (VLPs) with repeated antigens also constitute an effective preventive strategy for EV71 infections, with safety and productivity advantages. We previously developed a fusion protein composed with truncated peptides of the EV71 capsid protein, which assembled into spherical particles. This study aimed to assess the immunoprotective effects of this fusion protein as a vaccine candidate in a mouse model of EV71 infection.
METHODS
To evaluate the protective effect of fusion protein vaccine candidate, neonatal mice born by immunized female mice, as well as normal neonatal mice immunized twice were infected with EV71 virus. Whereafter, the survival rates, clinical scores and viral loads were measured.
RESULTS
The high dosage and booster immunization helped induce specific serum antibodies with high neutralization titers, which were transferred to neonatal mice, thereby facilitating effective resistance towards EV71 infection. An active immune response was also observed in neonatal mice which generated following immunization.
CONCLUSIONS
The present results suggest that this fusion protein is a suitable vaccine candidate in treating EV71 infections. | 10.1186/s12985-020-01328-8 |
pubmed_424_6325 | The term "chest pain with normal coronary arteries" encompasses a large number of different cardiac pathophysiological abnormalities, including impairment of coronary flow reserve, endothelial dysfunction, and early atherosclerosis that, in most cases, cannot be readily differentiated one from the other. To study early coronary atherosclerosis, physicians must look beyond contrast filled arteries (so called lumenology). Angiograms cannot evaluate the vessel wall, plaque distribution and composition or other morphology. Plaques are often angiographically not visible due to their small size and compensatory enlargement (outward remodeling) of the coronary arteries. As a result, the search for an underlying atherosclerotic process remains ongoing. Available clinical studies showed that many patients with chest pain and normal angiography have early atherosclerosis as documented by intravascular ultrasound imaging, reduced coronary flow reserve and coronary endothelial dysfunction. Additional studies showed that patients presenting with normal coronary angiography have recurrent coronary events at long-term follow up. Research to determine if improved diagnosis and treatment of quantitatively low degrees of atherosclerosis lead to improved outcomes of patients with normal angiography should be undertaken. | 10.1007/s00059-005-2659-8 |
pubmed_759_11583 | The fidelity of DNA synthesis as determined by the misincorporation of the base analogue 2-aminopurine in competition with adenine has been measured as a function of deoxynucleoside triphosphate substrate concentrations using purified mutator (L56), antimutator (L141), and wild type (T4D) T4 DNA polymerases. Although the rates of both incorporation and turnover of aminopurine and adenine decrease as substrate concentrations are decreased, the ratio of turnover/polymerase activity is increased. Thus, the nuclease/polymerase ratio of each of these three DNA polymerases can be controlled. The misincorporation of aminopurine decreases with decreasing substrate concentrations such that all three enzymes approach nearly identical misincorporation frequencies at the lowest substrate concentration. The increased accuracy of DNA synthesis corresponds to conditions producing a high nuclease/polymerase ratio. The misinsertion frequency for aminopurine is independent of substrate concentrations and enzyme phenotype; therefore, the increased accuracy of DNA synthesis with decreasing substrate concentrations is shown to be a result of increased nuclease activity and not increased polymerase or nuclease specificity. The data are analyzed in terms of a kinetic model of DNA polymerase accuracy which proposes that discrimination in nucleotide insertion and removal is based on the free energy difference between matched and mismatched base pairs. A value of 1.1 kcal/mol free energy difference, delta G, between adenine: thymine and aminopurine:thymine base pairs is predicted by model analysis of the cocentration dependence of aminopurine misincorporation and removal frequencies. An independent estimate of this free energy difference based on the 6-fold higher apparent Km of T4 DNA polymerase for aminopurine compared to adenine also gives a value of 1.1 kcal/mol. It is shown that the aminopurine misinsertion frequency for an enzyme having either extremely low 3'-exonuclease activity, Escherichia coli DNA polymerase I, or no measurable exonuclease activity, calf thymus DNA polymerase alpha, is 12 to 15%, which is similar to that for the T4 polymerases and consistent with delta G approximately 1.1 kcal/mol. | pubmed_759_11583 |
pubmed_697_15867 | PURPOSE
This work demonstrates the in vivo application of a T2 relaxation based total water content (TWC) measurement technique at 3T in healthy human brain, and evaluates accuracy using simulations that model brain tissue. The benefit of using T2 relaxation is that it provides simultaneous measurements of myelin water fraction, which correlates to myelin content.
METHODS
T2 relaxation data was collected from 10 healthy human subjects with a gradient and spin echo (GRASE) sequence, along with inversion recovery for T1 mapping. Voxel-wise T2 distributions were calculated by fitting the T2 relaxation data with a non-negative least squares algorithm incorporating B1+ inhomogeneity corrections. TWC was the sum of the signals in the T2 distribution, corrected for T1 relaxation and receiver coil inhomogeneity, relative to either an external water standard or cerebrospinal fluid (CSF). Simulations were performed to determine theoretical errors in TWC.
RESULTS
TWC values measured in healthy human brain relative to both external and CSF standards agreed with literature values. Simulations demonstrated that TWC could be measured to within 3-4% accuracy.
CONCLUSION
In vivo TWC measurement using T2 relaxation at 3T works well and provides a valuable tool for studying neurological diseases with both myelin and water changes. | 10.1016/j.mri.2016.12.001 |
pubmed_854_12247 | The present study examined the applicability of the double ABCX model of family adjustment in explaining maternal adjustment to caring for a child diagnosed with Asperger syndrome. Forty-seven mothers completed questionnaires at a university clinic while their children were participating in an anxiety intervention. The children were aged between 10 and 12 years. Results of correlations showed that each of the model components was related to one or more domains of maternal adjustment in the direction predicted, with the exception of problem-focused coping. Hierarchical regression analyses demonstrated that, after controlling for the effects of relevant demographics, stressor severity, pile-up of demands and coping were related to adjustment. Findings indicate the utility of the double ABCX model in guiding research into parental adjustment when caring for a child with Asperger syndrome. Limitations of the study and clinical implications are discussed. | 10.1177/1362361305049033 |
pubmed_215_19445 | When heart transplantation is needed in newborns, brain death should be confirmed, and the heart should not be exposed to hypoxia. The anencephalic newborn has been presented as a donor in heart transplantation. It is important, therefore, to evaluate possible morphological differences in the hearts of anencephalic cases. In this study, muscle fibers were studied in 10 anencephalic and 10 normal fetuses (27-35 weeks) and the results were compared. Random samples were taken from the upper 1/3 of the right ventricle's posterior wall and processed for light microscopic examination. Thicknesses of the 100 myocardial muscle fibers for each fetus were evaluated. There was statistically no significant difference between the anencephalic and normal fetus groups and the sex groups. Morphological features of the transplant probably affects the performance of the heart after operation. The anencephalic fetuses could be unique donors for heart transplantation. | pubmed_215_19445 |
pubmed_1030_12285 | DNA methylation, a form of epigenetic gene regulation, is important for normal cellular function. In cells, proteins called DNA methyltransferases (DNMTs) establish and maintain the DNA methylation pattern. Changes to the normal DNA methylation pattern are linked to cancer development and progression, making DNMTs potential cancer drug targets. Thus, identifying and characterizing novel small molecule inhibitors of these enzymes is of great importance. This paper presents a protocol that can be used to screen for DNA methyltransferase inhibitors. The continuous coupled kinetics assay allows for initial velocities of DNA methylation to be determined in the presence and absence of potential small molecule inhibitors. The assay uses the methyl-sensitive endonuclease Gla I to couple methylation of a hemimethylated DNA substrate to fluorescence generation. This continuous assay allows for enzyme activity to be monitored in real time. Conducting the assay in small volumes in microtiter plates reduces the cost of reagents. Using this assay, a small example screen was conducted for inhibitors of DNMT1, the most abundant DNMT isozyme in humans. The highly substituted anthraquinone natural product, laccaic acid A, is a potent, DNA-competitive inhibitor of DNMT1. Here, we examine three potential small molecule inhibitors - anthraquinones or anthraquinone-like molecules with one to three substituents - at two concentrations to describe the assay protocol. Initial velocities are used to calculate the percent activity observed in the presence of each molecule. One of three compounds examined exhibits concentration-dependent inhibition of DNMT1 activity, indicating that it is a potential inhibitor of DNMT1. | 10.3791/62949 |
pubmed_17_2701 | PURPOSE OF REVIEW
Infections with the filarial nematodes affect more than 150 million people mainly in the tropics. The very successful efforts to control filarial infections, however, have to be sustained by new tools that require long-term commitment to research. This review, focusing on reports from 2002 and 2003, highlights recent advances in research on immunology, understanding of pathogenesis and drug development in lymphatic filariasis and onchocerciasis research with potential relevance to the generation of new tools for control.
RECENT FINDINGS
Dramatic improvement has been achieved in the control of lymphatic filariasis and onchocerciasis by vector control and mass treatment with microfilaricidal drugs. Additional tools that could help in regional elimination or, ultimately, eradication of filariasis may arise from the development of new drugs or a vaccine. Research into the immune responses mediating protection or pathology has provided new insights into the pathways that lead to effector function and immunosuppression, such as T regulatory responses, as well as into genetic predispositions from the host's side, and to the identification of vaccine candidates that show protection in animal models. Recognition of the role the Wolbachia endosymbionts may play in activating the innate immune system has altered our understanding of immunopathology of filariasis and adverse reactions to microfilaricidal drugs. Wolbachia spp. have also proven to be suitable targets for the development of a long-term sterilizing or potentially macrofilaricidal drug.
SUMMARY
This review summarizes recent developments in the control of filariasis, in particular lymphatic filariasis and onchocerciasis, as well as in modern research into the immunity of filariasis and new drug development that could lead to additional tools necessary for sustained success in filariasis control. | 10.1097/00001432-200310000-00006 |
pubmed_459_745 | Although magnetic resonance imaging has a high sensitivity for cerebral and spinal tumors, demonstration of small lesions can be difficult. In a patient with multiple extra- and intraspinal tumors due to neurofibromatosis generalisata, the use of the MRI contrast agent Gadolinium-DTPA resulted in a better differentiation especially of small lesions. High tumor contrast facilitated a safe localisation of the widespread disease using a fast imaging sequence (FLASH). | pubmed_459_745 |
pubmed_1132_22601 | OBJECTIVE
To determine prognostic role of NT-proBNP as predictor of 30 day-mortality and readmission in the elderly with acute heart failure (AHF) treated in Spanish Emergency Departments (EDs), and to analyse the confounding factors when the NT-proBNP value is interpreted.
MATERIAL AND METHODS
A multicentre and multi-purpose cohort study with prospective follow-up was conducted on all patients aged 65 years or older with AHF treated in Spanish EDs. The variables recorded include demographic characteristics, comorbidity, details of episode, and NT-proBNP value. The outcome variables were 30 day-mortality and readmission. An NT-proBNP ≥ 5,180 pg/ml was adopted as the cut-off limit. The statistical package SPSS 18.0 was used to analyse the data.
RESULTS
A total of 585 patients were included, with a mean age of 80.4 (SD: 6.9) years old. The cut-off NT-proBNP ≥ 5,180 pg/ml was independently associated with a severely impaired glomerular filtration (<30 ml/h) (P < .001) and severe episode (NYHA II-IV) (P = .012). The NT-proBNP area under curve (AUC) for 30 day-mortality was 0.71 (CI 95%: 0.63-0.77; P < .001) and for 30 day-readmission, was 0.50 (CI 95%: 0.45-0.56; P = .846). A multivariable analysis showed that the cut-off NT-proBNP ≥ 5,180 pg/ml was an independent factor associated with 30 day-mortality in the elderly with AHF attended in Spanish EDs.
CONCLUSIONS
The NT-proBNP value is associated with short-term mortality in the elderly with AHF attended in the EDs independently of the presence of confounding factors, such as the severity of the episode and glomerular filtration reduction, but not with 30 day-readmission. | pubmed_1132_22601 |
pubmed_37_2996 | The purpose of this study was to assess the additional value of combined fluorine 18 (18F)-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) in the follow-up of rectal cancer after surgery. Forty-eight examinations in 30 patients were evaluated retrospectively. CT and PET components were interpreted separately, and this was followed by a consensus reading. Sites of increased FDG uptake as well as PET/CT findings were categorized as benign (1), equivocal (2), or malignant (3). The standard of reference was histology or clinical and imaging follow-up for at least 6 months. Sensitivity, specificity, positive and negative predictive values, and accuracy for differentiating benign (14/31) from malignant (17/31) uptake sites in the small pelvis were 100%, 64%, 77%, 100%, and 84% for PET/CT, and 100%, 29%, 63%, 100%, and 68% for PET, respectively. Regarding extrapelvic abnormalities, PET/CT was able to distinguish benign (31/88) from malignant (57/88) with a sensitivity, specificity, positive and negative predictive values, and accuracy of 100%, 87%, 93%, 100%, and 95%, compared with 96%, 68%, 85%, 91%, and 86% for PET. The rare case of an FDG uptake of adrenal adenoma is documented. PET/CT is valuable in the staging of rectal cancer, particularly for excluding recurrent disease suspected by PET interpretation alone in a considerable number of patients. | pubmed_37_2996 |
pubmed_446_2000 | BACKGROUND
Atopy, a common disorder characterized by a sensitivity to allergic reactions, affects a large proportion of the adult population and, as with depression, is associated with immune-inflammatory pathway changes. We sought to determine the role of atopic disorders in depression using data from a randomly-selected, population-based study of men and women.
METHODS
Cross-sectional data derived from the Geelong Osteoporosis Study for 942 males and 1085 females were analyzed. Depression [major depressive disorder (MDD), minor depression and dysthymia] was assessed using the Structured Clinical Interview for DSM-IV-TR Research Version, Non-patient edition. Data on medical conditions, including atopic disorders (asthma, hay fever and eczema), smoking status, alcohol consumption, socioeconomic status, and physical activity were documented by self-report. Logistic regression modeling was used to explore the associations between atopic disorders and depression.
RESULTS
Atopic disorders were associated with a 59% increased likelihood of depression [gender and smoking-adjusted odds ratio (OR) 1:50, 95% CI 1.20-1.97]. Sub-group analyses revealed a similar pattern for those with MDD [gender and smoking-adjusted OR 1:54, 95% CI 1.22-1.94]. These associations were independent of socio-demographic characteristics, clinical and lifestyle factors.
LIMITATIONS
Reliance on self-report for allergic symptoms and cross-sectional nature of study.
CONCLUSION
This population-based study provides evidence of the potential contribution of allergic disorders to depression. Further research is required to elucidate the direction of this association and to further explicate its underlying physiology, including immune-inflammation markers. | pubmed_446_2000 |
pubmed_27_16604 | Angiotensin II has two major receptor subtypes, designated AT1 and AT2. Both have been detected in the heart of several species, but most of the known functions of angiotensin II seem to be mediated through the AT1 receptor. The major objective of this study was to specify the cell type on which the AT2 receptor is located in the atrium of human heart. Right atrial biopsies from patients with coronary artery disease were tested in membrane binding assays and found to contain high levels of angiotensin II receptor (820 +/- 175 fmol/mg), 82 +/- 2% of which was of the AT2 subtype. Cryostat sections of these biopsies were incubated with 125I-[Sar1,Ile8] angiotensin II in the presence of selective concentrations of the cold ligands losartan and CGP 42112A to detect the subtypes using microscopic autoradiography. High local densities of the AT2 receptor were observed. Comparison of the labelling patterns thus obtained with adjacent sections stained for vimentin, collagen, neurofilaments or acetylcholinesterase revealed that the high densities of AT2 receptor were always associated with fibrous tissue. However, the AT1 receptor was in general evenly distributed over the tissue at low concentrations. Higher local concentrations of this receptor subtype were observed on nervous tissue. The present finding of high densities of the AT2 receptor on fibroblasts at sites of fibrosis may have important clinical implications. Further studies to elucidate the function of this receptor subtype in the heart are therefore essential and the clinical consequences of the use of AT1 antagonists on post-infarction remodelling should be investigated. | 10.1006/jmcc.1996.0168 |
pubmed_770_2203 | A study describing the tissue reaction caused by the larval stage of Taenia solium in muscles was conducted on samples obtained from 28 infected pigs of different ages and provenance. Lesions were classified according to the severity of the tissue inflammatory response, larval degeneration and replacement by scar tissue in Grades 0-6. Results revealed that of a total of 296 larvae observed, 58 had degenerated, causing a severe granulomatous reaction in the host tissues (Grades 4 and 5) and finally fibrosis (Grade 6). Twenty-eight showed no inflammatory response (Grade 0). Judging from the histological findings, the eosinophil seems to be the determinant cell for the initiation of the destructive process of the larvae of T. solium. The results also suggest that a greater number (P less than 0.01) of degenerated larvae may be found in older pigs. | 10.1016/0304-4017(88)90019-2 |
pubmed_293_22210 | BACKGROUND
The benefits of combination antiretroviral (ARV) prophylaxis for infants whose HIV exposure is recognized near birth have been established, and the benefits of early ARV therapy are well known. Decisions about ARVs can be supported by the probability that the child has acquired HIV.
METHODS
Using 2005-2010 data from Enhanced Perinatal Surveillance of the Centers for Disease Control and Prevention, we developed a tool for use at birth to help predict HIV acquisition of HIV-exposed infants to support ARV management. A logistic regression model, fit using a fully Bayesian approach, was used to determine maternal variables predictive of infant HIV acquisition. We created a score index from these variables, established the sensitivity and specificity of each possible score, and determined the distribution of scores among infants, with and without HIV, in our study population.
RESULTS
Multivariable analysis of data from 8740 HIV-exposed infants (176 infected and 8564 uninfected) yielded 4 maternal variables in the perinatal HIV acquisition prediction model: sexually transmitted infection, substance use, last HIV viral load before delivery and ARV use. Using the regression coefficient estimates, we rescaled each possible score to make the maximum score equal to 100. For each score, sensitivity and specificity were determined; the area under the receiver operating characteristic curve was 0.79. Median index scores for infants with HIV and without HIV were 43 (first quartile 27 and third quartile 60), and 12 (first quartile, 0 and thirs quartile, 29), respectively.
CONCLUSIONS
Decisions to begin infants on 3 ARVs-whether considered therapeutic or prophylactic-can be supported by data available on the day of birth. | 10.1097/INF.0000000000002374 |
pubmed_308_6898 | Langmuir-Blodgett (LB) and drop-cast (DC) films prepared from [Ru(1)3][PF6]2 and Co4POM (1= 4,4'-bis((n)nonyl)-2,2'-bipyridine, Co4POM = K10[Co4(H2O)2(α-PW9O34)2]) have been evaluated as water oxidation catalysts and their electrocatalytic performances are reported; DC films evolve more O2 per unit area than LB films and the catalyst is stable on an FTO surface for ≈500-600 minutes. | 10.1039/c5cc09556e |
pubmed_6_25 | Paracoccidioidomycosis (PCM) is a systemic mycosis, endemic in Latin America, caused by fungi of the genus Paracoccidioides. The treatment of PCM is complex, requiring a long treatment period, which often results in serious side effects. The aim of this study was to screen for inhibitors of a specific target of the fungus that is absent in humans. Methylcitrate synthase (MCS) is a unique enzyme of microorganisms and is responsible for the synthesis of methylcitrate at the beginning of the propionate degradation pathway. This pathway is essential for several microorganisms, since the accumulation of propionyl-CoA can impair virulence and prevent the development of the pathogen. We performed the modeling and molecular dynamics of the structure of Paracoccidioides lutzii MCS (PlMCS) and performed a virtual screening on 89,415 compounds against the active site of the enzyme. The compounds were selected according to the affinity and efficiency criteria of in vitro tests. Six compounds were able to inhibit the enzymatic activity of recombinant PlMCS but only the compound ZINC08964784 showed fungistatic and fungicidal activity against Paracoccidioides spp. cells. The analysis of the interaction profile of this compound with PlMCS showed its effectiveness in terms of specificity and stability when compared to the substrate (propionyl-CoA) of the enzyme. In addition, this compound did not show cytotoxicity in mammalian cells, with an excellent selectivity index. Our results suggest that the compound ZINC08964784 may become a promising alternative antifungal against Paracoccidioides spp. Communicated by Ramaswamy H. Sarma. | 10.1080/07391102.2021.1930584 |
pubmed_176_1758 | Cystic fibrosis is caused by impaired ion transport due to mutated cystic fibrosis transmembrane conductance regulator, accompanied by elevated activity of the amiloride-sensitive epithelial Na(+) channel (ENaC). Here we show that knockout of the ubiquitin ligase Nedd4L (Nedd4-2) specifically in lung epithelia (surfactant protein C-expressing type II and Clara cells) causes cystic fibrosis-like lung disease, with airway mucus obstruction, goblet cell hyperplasia, massive inflammation, fibrosis, and death by three weeks of age. These effects of Nedd4L loss are likely caused by enhanced ENaC function, as reflected by increased ENaC protein levels, increased lung dryness at birth, amiloride-sensitive dehydration of lung explants, and elevated ENaC currents in primary alveolar type II cells analyzed by patch clamp recordings. Moreover, the lung defects were rescued with administration of amiloride into the lungs of young knockout pups via nasal instillation. Our results therefore suggest that the ubiquitin ligase Nedd4L can suppress the onset of cystic fibrosis symptoms by inhibiting ENaC in lung epithelia. | 10.1073/pnas.1010334108 |
pubmed_504_15544 | mHealth can be used to deliver interventions to optimize Health-related quality of life (HRQoL) of cancer patients. In this systematic-review and meta-analysis, we explored the possible impact of health interventions delivered via mHealth tools on HRQoL of cancer patients. The systematic literature search was performed on July 20, 2019, to identify studies that evaluated the impact of mHealth intervention on HRQoL of cancer patients. We identified 25 studies (17 randomized controlled trials and 8 pre-post design studies; 957 patients) that evaluated mHealth interventions. The most commonly studied mHealth interventions included physical activity/ fitness interventions (9 studies), cognitive behavioral therapy (6 studies), mindfulness/ stress management (3 studies). In the majority of studies, mHealth interventions were associated with an improved HRQoL of cancer patients. The meta-analysis of the identified studies supported the positive effect of mHealth interventions for HRQoL of cancer patients. mHealth interventions are promising for improving HRQoL of cancer patients. | 10.1016/j.critrevonc.2020.103123 |
pubmed_912_24078 | We show that the quasi-skutterudite superconductor Sr(3)Ir(4)Sn(13) undergoes a structural transition from a simple cubic parent structure, the I phase, to a superlattice variant, the I' phase, which has a lattice parameter twice that of the high temperature phase. We argue that the superlattice distortion is associated with a charge density wave transition of the conduction electron system and demonstrate that the superlattice transition temperature T(*) can be suppressed to zero by combining chemical and physical pressure. This enables the first comprehensive investigation of a superlattice quantum phase transition and its interplay with superconductivity in a cubic charge density wave system. | 10.1103/PhysRevLett.109.237008 |
pubmed_740_22172 | For diagnoses that require inputs from multiple players - patients, informal caregivers, health care professionals - a team approach to coordinating diagnostic care has the potential to improve outcomes. Taking a patient-system perspective helps elucidate important factors relevant to team-based diagnostic performance. These factors are conceptualized as a metaphoric playing field that has goals, players interacting, unavoidable uncertainties and influential social conditions specifically tied to the diagnosis phase of care. In terms of rules of the game, the patient-system interaction might be guided by application of Gittell and colleague's relational coordination concepts, and understood within a broader social network framework of diagnosis, adapted from work by Berkman and colleagues. Patient-centered metrics are also needed to monitor the success of diagnosis. | pubmed_740_22172 |
pubmed_314_10648 | Detailed proteomic analyses of mammalian olfactory and rod photoreceptor sensory cilia are now available, providing an inventory of resident ciliary proteins and laying the foundation for future studies of developmental and spatiotemporal changes in the composition of sensory cilia. Cilia purification methods that were elaborated and perfected over several decades were essential for these advances. In contrast, the proteome of primary cilia is yet to be established, because purification procedures for this organelle have been developed only recently. In this chapter, we review current techniques for the purification of olfactory and photoreceptor cilia, and evaluate methods designed for the selective isolation of primary cilia. | 10.1016/S0091-679X(08)94004-8 |
pubmed_700_13287 | The gamma-aminobutyric acid (GABA) inhibiting properties of the beta-substituted gamma-butyrolactone convulsant, beta-isopropyl-gamma-butyrolactone (beta IPGBL), were studied using gigaseal recording techniques in cultured chick spinal cord neurons. beta IPGBL produced a dose-dependent inhibition of GABA currents with half maximal effect at 92 microM. The effects of beta IPGBL were immediate and completely reversible within minutes after exposure. The inhibition by beta IPGBL showed mixed competitive and non-competitive features with little voltage-dependence. beta IPGBL did not alter the GABA reversal potential nor the degree of GABA desensitization. At a single-channel level, beta IPGBL markedly diminished the opening of GABA channels and decreased the mean channel open time by 30-40% without affecting the amplitude of the single-channel current. | 10.1016/0006-8993(89)90352-1 |
pubmed_670_6214 | Pseudomonas cepacia G4 possesses a novel pathway of toluene catabolism that is shown to be responsible for the degradation of trichloroethylene (TCE). This pathway involves conversion of toluene via o-cresol to 3-methylcatechol. In order to determine the enzyme of toluene degradation that is responsible for TCE degradation, chemically induced mutants, blocked in the toluene ortho-monooxygenase (TOM) pathway of G4, were examined. Mutants of the phenotypic class designated TOM A- were all defective in their ability to oxidize toluene, o-cresol, m-cresol, and phenol, suggesting that a single enzyme is responsible for conversion of these compounds to their hydroxylated products (3-methylcatechol from toluene, o-cresol, and m-cresol and catechol from phenol) in the wild type. Mutants of this class did not degrade TCE. Two other mutant classes which were blocked in toluene catabolism, TOM B-, which lacked catechol-2,3-dioxygenase, and TOM C-, which lacked 2-hydroxy-6-oxoheptadienoic acid hydrolase activity, were fully capable of TCE degradation. Therefore, TCE degradation is directly associated with the monooxygenation capability responsible for toluene, cresol, and phenol hydroxylation. | 10.1128/aem.57.7.1935-1941.1991 |
pubmed_542_1428 | The multistage nature of carcinogenesis observed in a variety of systems has been linked experimentally to the sequential activation and subsequent cooperation of oncogene proteins. Cellular transformation resulting from cooperative interactions between activated oncogenes has been described previously for cultured primary cells and certain established cell lines. Our laboratory is using the mouse embryonic cell line C3H10T1/2 to investigate cooperative transformation mediated by the activated human H-ras gene and several nuclear oncogenes from both viral and cellular sources. Oncogene cooperation in C3H10T1/2 is marked by an increase in focus number and an alteration in focus morphology. Although ras cooperates with myc and fos oncogenes to transform C3H10T1/2 fibroblasts, cooperative transformation is not observed in cells similarly co-transfected with the H-ras and E1A oncogenes. This result appears to be due to a growth inhibitory effect of the EIA gene product on C3H10T1/2 cells. The observed cooperation between the H-ras and MC29 viral gag-myc oncogenes has been used along with site-directed mutagenesis of the gag-myc gene to identify two structural regions within the gag-myc protein that mediate ras/myc cooperativity. In addition, the gag-myc mutants generated for these cooperation studies have been used to map the nuclear localization signal of the gag-myc protein and relate the proper cellular location of the protein to its activity in several transformation assays. | pubmed_542_1428 |
pubmed_444_16407 | BACKGROUND
Patients with isolated ankle osteoarthritis (OA) often demonstrate disturbed ankle biomechanics during walking. Clinicians often believe that this triggers the distal foot joints to compensate these altered ankle biomechanics and that these foot joints are consequently subjected to degenerative joint diseases due to overuse.
QUESTIONS/PURPOSES
Do patients with isolated ankle OA differ from those without ankle OA in terms of (1) ankle and foot joint kinematics and (2) ankle and foot joint kinetics as measured using three-dimensional (3-D) gait analysis? (3) Do these patients demonstrate compensatory strategies in their Chopart, Lisfranc, or first metatarsophalangeal joints in terms of increased joint kinematic and kinetic outputs?
METHODS
Between 2015 and 2018, we treated 110 patients with unilateral ankle OA, and invited all of them to participate in the gait analysis laboratory. Of those, 47% (52) of patients did so, and of these, 16 patients met the inclusion criteria for this study, which were (1) diagnosis of unilateral ankle OA; (2) absence of radiographical signs of OA in the contralateral foot or lower limbs; (3) ability to walk at least 100 m without rest; and (4) being older than 18 years of age. A control group (n = 25) was recruited through intranet advertisements at the University Hospitals of Leuven. Participants were included if their age matched the age-range of the patient group and if they had no history of OA in any of the lower limb joints. Patients were slightly older (55.9 ± 11.2 years), with a slightly higher BMI (28 ± 6 kg/m2) than the control group participants (47.2 ± 4.4 years; p = 0.01 and 25 ± 3 kg/m2; p = 0.05). All participants underwent a 3-D gait analysis, during which a multisegment foot model was used to quantify the kinematic parameters (joint angles and ROM) and the kinetic parameters (rotational forces or moments), as well as power generation and absorption in the ankle, Chopart, Lisfranc, and first metatarsophalangeal joints during the stance phase of walking. Peak values were the maximum and minimum values of waveforms and the latter were time-normalized to 100% of the stance phase.
RESULTS
Regarding joint kinematics, patients demonstrated a sagittal plane ankle, Chopart, Lisfranc, and first metatarsophalangeal joint ROM of 11.4 ± 3.1°, 9.7 ± 2.7°, 8.6 ± 2.3° and 34.6 ± 8.1°, respectively, compared with 18.0 ± 2.7° (p < 0.001), 13.9 ± 3.2° (p < 0.001), 7.1 ± 2.0° (p = 0.046) and 38.1 ± 6.5° (p = 0.15), respectively, in the control group during the stance phase of walking. With regard to joint kinetics in the patient group, we found a mean decrease of 1.3 W/kg (95% CI confidence interval 1.0 to 1.6) (control group mean: 2.4 ± 0.4 W/kg, patient group mean: 1.1 ± 0.5 W/kg) and 0.8 W/kg (95% CI 0.4 to 1.0) (control group mean: 1.5 ± 0.3 W/kg, patient group mean: 0.7 ± 0.5 W/kg) of ankle (p < 0.001) and Chopart (p < 0.001) joint peak power generation. No changes in kinetic parameters (joint moment or power) were observed in any of the distal foot joints.
CONCLUSION
The findings of this study showed a decrease in ankle kinematics and kinetics of patients with isolated ankle OA during walking, whereas no change in kinematic or kinetic functions were observed in the distal foot joints, demonstrating that these do not compensate for the mechanical dysfunction of the ankle.
CLINICAL RELEVANCE
The current findings suggest that future experimental laboratory studies should look at whether tibiotalar joint fusion or total ankle replacement influence the biomechanical functioning of these distal joints. | 10.1097/CORR.0000000000001443 |
pubmed_472_11904 | Beta-blockers constitute standard therapy for heart failure with reduced ejection. However, their role in patients with preserved ejection fraction is not clear. Searching in Epistemonikos database, which is maintained by screening multiple databases, we identified four systematic reviews covering 19 primary studies, including seven randomized trials answering the question of this summary. We combined the evidence using meta-analysis and generated a summary of findings table following the GRADE approach. We concluded the use of beta-blockers probably leads to little or no difference in the risk of death or hospitalization in patients with heart failure with preserved ejection fraction. | 10.5867/medwave.2016.6593 |
pubmed_912_24606 | The gene products of the five-membered PRS gene family in Saccharomyces cerevisiae have been shown to exist as three minimal functional entities, Prs1/Prs3, Prs2/Prs5, and Prs4/Prs5, each capable of supporting cell viability. The Prs1/Prs3 heterodimer can be regarded as the most important because its loss causes temperature sensitivity. It has been shown that the GFP signal generated by an integrated GFP-Prs1 construct is lost in the absence of Prs3. In addition to interacting with Prs3, Prs1 also interacts with Slt2, the MAPK of the cell wall integrity (CWI) pathway. Lack of the nonhomologous region (NHR1-1) located centrally in Prs1 abolished the temperature-induced increase in Rlm1 expression. Furthermore, in vitro point mutations generated in PRS1 corresponding to missense mutations associated with human neuropathies or in the divalent cation and/or 5-phosphoribosyl-1(α)-pyrophosphate binding sites also display increased Rlm1 expression at 30 °C and 37 °C and most give rise to caffeine sensitivity. Human PRPS1 cDNA cannot rescue the synthetic lethality of a prs1Δ prs5Δ strain because it lacks sequences corresponding to NHR1-1 of yeast Prs1. The correlation between caffeine sensitivity and increased basal expression of Rlm1 in the altered versions of PRS1 can be extended to their inability to rescue the synthetic lethality of a prs1Δ prs5Δ strain implying that impaired CWI may contribute to the observed loss of viability. | 10.1111/1567-1364.12033 |
pubmed_1021_16468 | The study aimed at evaluating an effect of intraperitoneal furosemide on plasma proteins such as albumins, globulins, IgG and IgA and their loss during dialysis. An experiment involved 18 patients with critical renal failure treated with intermittent peritoneal dialyses. Furosemide was administered intraperitoneally with dialysing fluid (40 mg/1) in a total dose of 240 mg. Each patient underwent 2 dialyses of 14 exchanges each. The first dialysis without furosemide served as a control of plasma protein loss during conventional dialysis with a fluid of 369 mOsm/kg at flow rate 2.4 l/hour. Furosemide was given during the second dialysis during three consecutive exchanges. An effect of furosemide on plasma proteins was compared with the results obtained before and after its administration. It was found that furosemide did not change plasma proteins levels and does not increase their loss during exchanges of dialysing fluid containing this drug; during dialysing fluid exchanges without furosemide some indices of IgG and IgA dialysis are significantly decreased due to an increase in ultrafiltration following furosemide cessation. It is important for the increase in intermittent peritoneal dialyses efficiency with the aid of furosemide that its short-term administration does not increase proteins loss during dialysis, if their molecular weight is not exceeding 69,000. | pubmed_1021_16468 |
pubmed_454_23820 | Prior work has proposed the use of ultrasonic angle-beam shear wave techniques to detect cracks of varying angular location around fastener sites by generating and detecting creeping waves. To better understand the nature of the scattering problem and quantify the role of creeping waves in fastener site inspections, a 3D analytical model was developed for the propagation and scattering of an obliquely incident plane shear wave from a cylindrical cavity with arbitrary shear wave polarization. The generation and decay of the spiral creeping waves was found to be dependent on both the angle of incidence and polarization of the plane shear wave. A difference between the angle of displacement in 3D and the direction of propagation for the spiral creeping wave was observed and attributed to differences in the curvature of the cavity surface for the tangential and vertical (z) directions. Using the model, practical insight was presented on measuring the displacement response in the far-field from the hole. Both analytical and experimental results highlighted the value of the diffracted and leaky spiral creeping wave signals for nondestructive evaluation of a crack located on the cavity. Last, array and signal processing methods are discussed to improve the resolution of the weaker creeping wave signals in the presence of noise. | 10.1121/1.3583540 |
pubmed_730_2279 | In this brief review we examine the effects of resistance training on energy expenditure. The components of daily energy expenditure are described, and methods of measuring daily energy expenditure are discussed. Cross-sectional and exercise intervention studies are examined with respect to their effects on resting metabolic rate, physical activity energy expenditure, postexercise oxygen consumption, and substrate oxidation in younger and older individuals. Evidence is presented to suggest that although resistance training may elevate resting metabolic rate, it does not substantially enhance daily energy expenditure in free-living individuals. Several studies indicate that intense resistance exercise increases postexercise oxygen consumption and shifts substrate oxidation toward a greater reliance on fat oxidation. Preliminary evidence suggests that although resistance training increases muscular strength and endurance, its effects on energy balance and regulation of body weight appear to be primarily mediated by its effects on body composition (e.g., increasing fat-free mass) rather than by the direct energy costs of the resistance exercise. | 10.1123/ijsn.8.2.143 |
pubmed_1123_13790 | AIM OF THE STUDY
To analyze the short-term efficacy of the Vocational Perspective programme for patients identified as having extensive work-related problems during rheumatology or orthopaedic inpatient rehabilitation. The primary objectives of the programme on patient level are to convey information about the legal provisions regarding earning incapacity and occupational reintegration, to suggest strategies for dealing with one's own occupational situation, and to strengthen the motivation to stay employed. The programme is explicitly designed for patients who wish to retire or have applied for a pension. On the systemic level, the main goals are to facilitate doctor-patient communication and to increase rehabilitation teams' awareness of occupational problems.
METHODS
In a controlled quasi-experimental design, 359 subjects were consecutively assigned to either the control group (CG, n=177) or the intervention group (IG, n=182). The control group received standard care only, whereas the intervention group additionally participated in the 5-part Vocational Perspective programme. Evaluation criteria were assessed by questionnaire at the beginning (t1) and at end of rehabilitation (t2). Survey participation was 92.2% at t2. The socio-medically relevant knowledge status was objectively documented using a specially designed knowledge questionnaire. Aspects of treatment satisfaction were evaluated using individual items, and the subjective prognosis of gainful employment was assessed using the Subjective Prognosis of Gainful Employment (SPE) scale. Facilitation of communication between doctor and patient was operationalized at patient level in terms of patient satisfaction with medical care, and increased awareness of the rehabilitation team was operationalized in terms of the rate of recommendations to apply for vocational reintegration (LTA) services at discharge. Emotional and functional parameters were exploratively analyzed (anxiety and depression using the IRES 3.1 scales, and subjectively experienced pain-related impairment using the Pain Disability Index).
RESULTS
Scores for subjective satisfaction with job-related information, medical care, socio-medical assessment, and the overall benefits of rehabilitation were significantly higher in the intervention group than in the control group. IG subjects moreover were better able to use the rehabilitation measure to clarify their occupational situation and exhibited significantly greater improvement of socio-medically relevant knowledge. Age proved to be an important predictor of change in a patient's subjective prognosis for gainful employment (SPE): A positive change in SPE was observed in both groups in subjects under 50, in those aged 50 and older, however, only in the intervention group. No differences between the two groups were observed in terms of functional and emotional parameters (e. g., disability through pain, anxiety, and depression). A total of 60% of the subjects received a recommendation at discharge to apply for vocational reintegration services, the proportion however was significantly higher in the IG.
CONCLUSIONS
The Vocational Perspective programme met the patients' high demand for information on relevant socio-medical facilities and services regarding career change and facilitated communication between the doctor and patient by creating greater transparency. The improvement of subjective prognosis for gainful employment observed in the subgroup of older patients indicates that specialized interventions are needed in precisely this disadvantaged group in order to improve their own vocational expectations and thus to improve their chances of reintegration into work life. The high rate of recommendations to apply for vocational reintegration services suggests that rehabilitation teams already have a high awareness of job-related problems even under “usual care” conditions. | 10.1055/s-0031-1299692 |
pubmed_942_8611 | Scutella separated from germinating grains of barley (Hordeum vulgare L.), wheat (Triticum aestivum L.), rice (Oryza sativa L.), and maize (Zea mays L.) took up the four amino acids and the three peptides tested from incubation media. The uptake of amino acids by wheat scutella was similar to that of barley scutella and was via at least four uptake systems: two nonspecific amino acid uptake systems, one system specific for proline, and another system specific for basic amino acids. The scutellum of rice apparently has two nonspecific systems and a system specific for the basic amino acids, but the proline-specific system is lacking. The scutellum of maize seems to have the same systems as the scutellum of rice, but one (or both) of the nonspecific systems differs from that of the other species studied in taking up arginine only slowly. No great differences were observed in the uptake of peptides in the four species studied. The rates of uptake of different amino acids and peptides were of the same order of magnitude in the four cereals. The fact that carboxypeptidase activities in the endosperms of wheat and barley are 20-to 100-fold higher than those in rice and maize, does thus not seem to be reflected in the uptake properties of the scutella. | 10.1104/pp.89.4.1285 |
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