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pubmed_177_11930
The electrochemistry of pyridines in acidic solution is dominated by a 'weak acid' reduction on the cyclic voltammetry timescale. Here we show that electrochemical hydrogenation of a benzannulated pyridine, phenanthridine (1), to the biomimetic hydride donor 1,2-dihydrophenanthridine (1-H2) can occur selectively at glassy carbon electrodes over longer timescales of potentiostatic electrolysis.
10.1039/c7cc07907a
pubmed_596_15299
Herein we report the synthesis of propanoic acid functionalized ionic liquids (ILs) with various lengths of alkyl chain on the imidazole ring. The synthesized propanoic acid functionalized ILs were used to dissolve Eu(2)O(3) (or Tb(4)O(7)) due to the formation of europium(III) (or terbium(III)) carboxylate, aimed to get soft luminescent materials combining the properties of ILs and attractive luminescent properties of lanthanide ions. The luminescent behavior of Eu(3+) and Tb(3+) in the ILs were investigated by luminescence spectroscopy. The affect of the alkyl chain on the luminescent behavior (the asymmetry parameter (R), the lifetime of (5)D(0), and the (5)D(0) quantum efficiency) of Eu(3+) has been discussed.
10.1002/asia.201000872
pubmed_257_21352
Cholecystokinin (CCK) mRNA was detected by in situ hybridization at high magnification in some rat brain regions where CCK octapeptide (CCK-8) is thought to produce its pharmacological effects. The labeling of the dentate gyrus and the sparse but intensively stained cells found in the CA1 layer, stratum radiatum and hilus could correspond to interneurons involved in hippocampal neural activity, in agreement with excitatory responses induced by local injection of CCK-8. The intense labeling of the Edinger-Westphal nucleus and more generally the presence of CCK mRNA in the periaqueductal gray and thalamus ventrobasal nuclei could account for the various effects of CCK in pain transmission.
10.1016/0304-3940(89)90325-x
pubmed_795_6010
11Beta-hydroxysteroid dehydrogenase 1 (11beta-HSD1) has been identified as a major detoxification enzyme of one of the most potent tobacco smoke-derived carcinogens, NNK. If not metabolized by 11beta-HSD1, activation of NNK by cytochrome p450 mono-oxidase 2D6 (CYP2D6) results in an electrophile intermediate responsible for DNA damage. Interindividual variability in the expression of 11beta-HSD1 and CYP2D6 has been found to influence the susceptibility to lung cancer. The aim of this study was to compare 11beta-HSD1 mRNA expression and CYP2D6 metabolizer status in pharyngeal tissues of patients with oropharyngeal carcinoma and controls. In 20 patients with oropharyngeal cancer and 15 non-smoking controls, the 11beta-HSD1 mRNA expression was assessed with RT-PCR. The frequency of genetic polymorphisms of the CYP2D6 gene was assessed using RFLP. It was found that 11beta-HSD1 mRNA is expressed in human pharyngeal mucosa. It is upregulated in mucosa exposed to tobacco smoke. In tumour tissues, 11beta-HSD1 expression was significantly lower than in non-affected mucosa. The frequency distribution of CYP2D6 gene polymorphisms was similar in patients and controls. Chronic tobacco abuse results in 11beta-HSD1 enzyme induction. A reduction of 11beta-HSD1 expression in tumour tissues could be a consequence of malignantly transformed cells. It remains unclear if the lower 11beta-HSD1 expression gives rise to an increased rate of additional mutations.
10.1046/j.1365-2273.2002.00609.x
pubmed_962_19751
Abdominal tuberculosis is still a medical problem in developing countries. The clinical presentation of tuberculous (TB) peritonitis may be similar to that of peritoneal carcinomatosis. Therefore, its diagnosis is rather difficult only with laboratory investigations. Ascitic fluid adenosine deaminase (ADA) activity has been proposed as a useful diagnostic test in tuberculous peritonitis, as many studies reported high ADA levels in TB peritonitis. On the other hand, ADA activity is usually lower in peritoneal carcinomatosis and malignant ascites. This study described a patient with non-Hodgkin lymphoma with elevated (67 U L(-1)) ADA levels and clinical signs mimicking peritoneal tuberculosis. On admission, this study focused on the high value of ADA in ascites and strongly suspected TP. Although anti-tuberculous agents were initiated, his general condition did not improve. Finally, laparoscopic peritoneal biopsy was performed and non-Hodgkin lymphoma diagnosed. In the light of these findings, ADA level may not reflect TB peritonitis in the absence of histopathological examination. Therefore, non-Hodgkin lymphoma should be kept in mind in the differential diagnosis in patients with high ascitic fluid ADA levels and in non-responders to anti-tuberculosis treatment.
10.1080/10428190500395472
pubmed_552_18748
A study is presented of the blood plasma level of opioid peptides in patients with progressive stenocardia. Results indicate non-homogeneity of the patients concerning the content of neuropeptides. Two subgroups were singled out: 1. patients with progressive stenocardia of exertion in which beta-endorphin and leucin-enkephalin were above normal; 2. patients with a severe course of ischemic heart disease. Here the content of same peptides was lower than in the compared group. Similar dependence of changes of the content of methionine-enkephalin was not revealed.
pubmed_552_18748
pubmed_703_12498
OBJECTIVE To establish the diagnostic validity of sensory overresponsivity (SOR), there is a need to document rates of SOR and the co-occurrence of SOR with other psychiatric disorders. Although this was not a diagnostic study of SOR, this study was designed to investigate rates of elevated SOR symptoms and associations between elevated SOR symptoms, psychiatric disorder status, and family impairment. METHOD From a larger birth cohort followed from infancy to school age, 338 children aged 7 to 10 years (51% boys, 49% girls) and their parents participated in an intensive assessment. Parents were interviewed with the Diagnostic Interview Schedule for Children (DISC) and completed the SensOR inventory and the Family Life Impairment Scale. RESULTS Approximately one-fifth (21.2%) of children had elevated SOR symptoms. One-fourth (24.3%) of those with an elevated SOR score met criteria for a DSM-IV diagnosis, and 25.4% of children with a DSM-IV diagnosis had an elevated SOR score. Parents of children with elevated SOR alone reported a similar number of restrictions in family life as parents of those with an internalizing and/or externalizing diagnosis. SOR predicted concurrent family impairment above and beyond DSM diagnostic status and socio-demographic risk. CONCLUSIONS Elevated SOR occurs in the absence of other psychiatric conditions and is associated with impairment in family life. Services for children with comorbid elevated SOR and an externalizing disorder are needed to address the extremely high level of family impairment reported.
10.1016/j.jaac.2011.09.010
pubmed_351_18695
The oligonucleotides d[(G-A)7G] and d[(G-A)12G] self-associate under physiological conditions (10 mM MgCl2, neutral pH) into a stable double-helical structure (psRR-DNA) in which the two polypurine strands are in a parallel orientation in contrast to the antiparallel disposition of conventional B-DNA. We have characterized psRR-DNA by gel electrophoresis, UV absorption, vacuum UV circular dichroism, monomer-excimer fluorescence of oligonucleotides end-labelled with pyrene, and chemical probing with diethyl pyrocarbonate and dimethyl sulfate. The duplex is stable at pH 4-9, suggesting that the structure is compatible with, but does not require, protonation of the A residues. The data support a model derived from force-field analysis in which the parallel-stranded d(G-A)n helix is right-handed and constituted of alternating, symmetrical Gsyn.Gsyn and Aanti.Aanti base pairs with N1H...O6 and N6H...N7 hydrogen bonds, respectively. This dinucleotide structure may be the source of a negative peak observed at 190 nm in the vacuum UV CD spectrum, a feature previously reported only for left-handed Z-DNA. The related sequence d[(GAAGGA)4G] also forms a parallel-stranded duplex but one that is less stable and probably involves a slightly different secondary structure. We discuss the potential intervention of psRR-DNA in recombination, gene expression and the stabilization of genomic structure.
10.1002/j.1460-2075.1992.tb05463.x
pubmed_76_12473
The neurokinin-1 (NK-1, substance P) receptor belongs to the class of seven transmembrane domain (7-TM) receptors that interact with cellular effector systems via guanine nucleotide binding regulatory proteins (G-proteins). In this study, coupling mechanisms of functional NK-1 receptors endogenously expressed in a human astrocytoma cell line (U373MG) were analyzed. Stimulation with substance P (SP) resulted in 1) a rapid increase in inositol 1,4,5-trisphosphate (IP3) synthesis; 2) a rise in cytosolic free calcium concentration ([Ca2+]i); 3) induction of immediate early gene transcription as monitored by c-fos and c-jun expression; and 4) a significant increase in de novo DNA synthesis. Thus, the functional responses induced by stimulation of NK-1 receptors on U373MG strongly correlate with those observed after treatment of primary astrocytes with SP and make U373MG cells a useful in vitro model system for the analysis of NK-1 receptor function on astrocytes in vivo.
10.1002/glia.440060203
pubmed_618_23883
The Veterans Healthcare Administration (VA) has embraced patient safety and quality improvement in the quest to improve care for veterans. The New Mexico VA Health Care System introduced a new morbidity and mortality conference, called the Interdisciplinary Quality Improvement Conference (IQIC), using patient case presentations to focus on underlying systems in the clinical care environment. The revised conference design also effectively teaches the 6 Accreditation Council for Graduate Medical Education (ACGME) core requirements for resident education. A formal process was established for case selection, presentation, systems issue identification, tracking, and follow-up. The IQIC has enabled the identification of more than 20 system issues at the study institution. Outcome data show lasting improvement in system issues that were addressed by this mechanism. The VA IQIC is an effective method to both identify and correct systems issues that affect patient care and is an effective method for teaching residents the 6 ACGME requirements for residency education.
10.1177/1062860614555430
pubmed_910_12206
Emotional intelligence refers to the ability to identify and monitor emotions and remain aware of how emotions affect thoughts and actions. Emotional intelligence has been discussed as a better predictor of personal and occupational success than performance on intellectual intelligence tests. PROBLEM Despite the importance of one's emotional intelligence, BSN (Bachelor of Science in Nursing) nursing schools routinely admit candidates based on the student's cumulative college course grade point average (GPA). Nursing is a profession that requires one's ability to empathize, care, and react in emotionally sound manners. Is the GPA enough to determine if a student will evolve into a professional nurse? EXPLORATION This article will explore the routine admittance criteria for BSN nursing programs and propose the concept of using the emotional intelligence tool as an adjunct to the cumulative college course GPA. The emotional intelligence theory will be identified and applied to the nursing profession.
10.1111/nuf.12166
pubmed_248_16864
OBJECTIVE To measure arginine vasopressin (AVP) serum concentrations in critically ill patients. DESIGN Prospective study. SETTING Twelve-bed general and surgical intensive care unit in a tertiary, university teaching hospital. PATIENTS Two-hundred-thirty-nine mixed critically ill patients and 70 healthy volunteers. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Demographic data, hemodynamic variables, vasopressor drug requirements, blood gases, AVP serum concentrations within 24 hrs after admission, multiple organ dysfunction score, and outcome were recorded. Twenty-four hours after admission, study patients had significantly higher AVP concentrations (11.9 +/- 20.6 pg/mL) than healthy controls (0.92 +/- 0.38 pg/mL; p < .001). Males had lower AVP concentrations than females (9.7 +/- 19.5 vs. 15.1 +/- 20.6 pg/mL; p = .014). Patients with hemodynamic dysfunction had higher AVP concentrations than patients without hemodynamic dysfunction (14.1 +/- 27.1 vs. 8.7 +/- 10.8 pg/mL; p = .042). Patients after cardiac surgery (n = 96) had significantly higher AVP concentrations when compared to patients admitted for other diagnoses (n = 143; p < .001). AVP concentrations were inversely correlated with length of stay in the intensive care unit (correlation coefficient, -0.222; p = .002). There was no correlation between serum AVP concentrations and the incidence of shock or specific hemodynamic parameters. Four (1.7%) of the 239 study patients met criteria for an absolute AVP deficiency (AVP, <0.83 pg/mL), and 32 (13.4%) met criteria for a relative AVP deficiency (AVP, <10 pg/mL, and mean arterial pressure, <70 mm Hg). In shock patients, relative AVP deficiency occurred in 22.2% (septic shock), 15.4% (postcardiotomy shock), and 10% (shock due to a severe systemic inflammatory response syndrome) (p = .316). CONCLUSIONS AVP serum concentrations 24 hrs after intensive care unit admission were significantly increased in this mixed critically ill patient population. The lack of a correlation between AVP serum concentrations and hemodynamic parameters suggests complex dysfunction of the vasopressinergic system in critical illness. Relative and absolute AVP deficiency may be infrequent entities during acute surgical critical illness, mostly remaining without significant effects on cardiovascular function.
10.1097/01.ccm.0000198528.56397.4f
pubmed_1064_1575
Development of antiangiogenic therapies would be significantly facilitated by quantitative surrogate pharmacodynamic markers. Circulating peripheral blood endothelial cells (CECs) and/or their putative progenitor subset (CEPs) have been proposed but not yet fully validated for this purpose. Herein, we provide such validation by showing a striking correlation between highly genetically heterogeneous bFGF- or VEGF-induced angiogenesis and intrinsic CEC or CEP levels measured by flow cytometry, among eight different inbred mouse strains. Moreover, studies using genetically altered mice showed that levels of these cells are affected by regulators of angiogenesis, including VEGF, Tie-2, and thrombospondin-1. Finally, treatment with a targeted VEGFR-2 antibody caused a dose-dependent reduction in viable CEPs that precisely paralleled its previously and empirically determined antitumor activity.
10.1016/j.ccr.2004.11.023
pubmed_245_10805
Animals that live in conventional agroecosystems must cope with a variety of anthropogenic chemicals. Most of the focus of toxicology is on lethality, deformities, or short-term shifts in behavior. However, for animals that succeed in spite of their exposure, it is important to determine if long-term changes are brought on by their experience. We tested the hypothesis that contact with a commercial formulation of a glyphosate-based herbicide would affect the behavior of subsequent instars in the wolf spider, Pardosa milvina, a species that thrives in the agroecosystems of eastern United States. In one experiment, we housed females carrying egg sacs on a surface treated with the herbicide for 7 h. Then we monitored their activity and foraging of the offspring 4 weeks after emergence. We repeated the same tests on adults that had been housed with herbicide during their penultimate stage. In both studies, exposed spiders displayed higher levels of activity and greater capture success than their unexposed counterparts. Exposure of penultimate instar to herbicide had larger effects on the behavior of adult males than adult females. These results suggest that herbicides have the potential to adjust the behavior of individuals in the predator community. Thus, impact on the food web and their positive or negative potential for biological control may extend beyond their role in controlling weeds.
10.1016/j.chemosphere.2017.12.038
pubmed_575_6947
BACKGROUND There is no universally accepted treatment standard for idiopathic toe walking patients (ITW) in the current literature. None of the established methods provide homogenous satisfying results. In our department we treat ITW patients with lower leg orthoses with a circular foot unit for a total of 16 weeks. In this study we reviewed our database to evaluate the success of our treatment protocol for a 24 months follow up period. RESULTS Twenty-two patients were included in this study. Age at the beginning of treatment was 7.0 years +/- 2.9 (range 2.5-13.1). Percentage of ITW at the beginning of treatment according to the perception of the parents was 89% +/- 22.2 (range 50-100). Immediately after the treatment with our device, percentage of ITW dropped to 11% +/- 13.2 (range 0-50). After 12 months, 73% of the patients (16/22) walked completely normal or showed ITW less than 10% of the day. After 24 months, 64% of the patients kept a normal gait (14/22). CONCLUSION This study provides evidence that the treatment of idiopathic toe walking with lower leg orthoses with a circular foot unit results in satisfying long-term results in two thirds of the patients.
10.1186/s12891-021-04327-0
pubmed_453_17768
The status quo of infectious diseases associated with hematological malignancies was examined for clinical consideration. In addition, in vitro antibacterial activities and combination effects were also examined by means of various isolated strains derived from sepsis. In clinical practice, 76% of the fevers in patients with hematological malignancies was attributed to infectious diseases mainly involving "fever with granulocytopenia", sepsis, and pneumonia. The detection rate of causal pathogen remained at a low level and more than half of the causes of death were infectious diseases. In the in vitro examination, a favorable antibacterial effect was noted with vancomycin (VCM) for methicillin resistant Staphylococcus aureus (MRSA) and Enterococcus spp., imipenem (IPM) for methicillin sensitive S. aureus (MSSA), and ciprofloxacin, amikacin (AMK), and IPM for Pseudomonas aeruginosa and intestinal flora. But its clinical effect is not enough. Synergic and/or additive effect can be expected by combining IPM with VCM for MRSA and Enterococcus spp., and IPM with AMK for P. aeruginosa. These combination therapies were considered to be optimal as antibacterial chemotherapy for infectious diseases associated with hematological malignancies.
10.11150/kansenshogakuzasshi1970.71.72
pubmed_151_26040
The National Institute of Mental Health launched the Research Domain Criteria (RDoC) initiative to better understand dimensions of behavior and identify targets for treatment. Examining dimensions across psychiatric illnesses has proven challenging, as reliable behavioral paradigms that are known to engage specific neural circuits and translate across diagnostic populations are scarce. Delay discounting paradigms seem to be an exception: they are useful for understanding links between neural systems and behavior in healthy individuals, with potential for assessing how these mechanisms go awry in psychiatric illnesses. This article reviews relevant literature on delay discounting (or the rate at which the value of a reward decreases as the delay to receipt increases) in humans, including methods for examining it, its putative neural mechanisms, and its application in psychiatric research. There exist rigorous and reproducible paradigms to evaluate delay discounting, standard methods for calculating discount rate, and known neural systems probed by these paradigms. Abnormalities in discounting have been associated with psychopathology ranging from addiction (with steep discount rates indicating relative preference for immediate rewards) to anorexia nervosa (with shallow discount rates indicating preference for future rewards). The latest research suggests that delay discounting can be manipulated in the laboratory. Extensively studied in cognitive neuroscience, delay discounting assesses a dimension of behavior that is important for decision-making and is linked to neural substrates and to psychopathology. The question now is whether manipulating delay discounting can yield clinically significant changes in behavior that promote health. If so, then delay discounting could deliver on the RDoC promise.
10.1017/S0033291718001770
pubmed_675_577
Planning and implementing surge capacity in healthcare services is challenging. The evolving nature of viral transmission makes it difficult to predict the potential impact on the health system and the readiness of healthcare managers and professional staff in responding to system transformation and consequential impacts. This is compounded by sudden increased demands in the types of work required. Guidance for implementing targeted strategies for health systems and services should include evidence that considers the feasibility, appropriateness, meaningfulness and effectiveness of healthcare practices at both the system and organization level. This is consistent with the Joanna Briggs Institute (JBI) model of evidence synthesis and translation. Evidence-based decision-making is a core management competency for health service leadership and the mechanism for improving the quality of management decisions, and hence better service delivery, effectiveness and efficiency. Human resources are the most important asset in crisis management. Health managers must create responsive surge capacity by quantifying existent human and material resources and the shortfall needs required to meet anticipated additional demand. We believe a multifaceted approach is the key to developing systemic surge capacity within the heath sector when faced with the management of crises such as pandemics. We explore and discuss the desirability of strategies based on the JBI model of evidence synthesis and implementation with a view to encouraging the creation of registries and follow-up systems. We believe this will encourage the effective use of human resources including the upskilling in how future crises may be addressed.
10.1097/XEB.0000000000000256
pubmed_200_15011
It is known that spermatogenic disorders are associated with genetic deficiency, although the primary mechanism is still unclear. It is difficult to demonstrate the molecular events occurring in testis, which contains germ cells at different developmental stages. However, transcriptomic methods can help us reveal the molecular drive of male gamete generation. Many transcriptomic studies have been performed on rodents by utilizing the timing of the first wave of spermatogenesis, which is not a suitable strategy for research in fertile men. With the development of separation methods for male germ cells, transcriptome research on the molecular drive of spermatogenesis in fertile men has seen great progress, and the results could be ultimately applied to improve the diagnosis and treatment for male infertility.
10.4103/1008-682X.159721
pubmed_262_11479
DNA supercoiling plays a major role in many cellular functions. The global DNA conformation is however intimately linked to local DNA-DNA interactions influencing both the physical properties and the biological functions of the supercoiled molecule. Juxtaposition of DNA double helices in ubiquitous crossover arrangements participates in multiple functions such as recombination, gene regulation and DNA packaging. However, little is currently known about how the structure and stability of direct DNA-DNA interactions influence the topological state of DNA. Here, a crystallographic analysis shows that due to the intrinsic helical chirality of DNA, crossovers of opposite handedness exhibit markedly different geometries. While right-handed crossovers are self-fitted by sequence-specific groove-backbone interaction and bridging Mg(2+) sites, left-handed crossovers are juxtaposed by groove-groove interaction. Our previous calculations have shown that the different geometries result in differential stabilisation in solution, in the presence of divalent cations. The present study reveals that the various topological states of the cell are associated with different inter-segmental interactions. While the unstable left-handed crossovers are exclusively formed in negatively supercoiled DNA, stable right-handed crossovers constitute the local signature of an unusual topological state in the cell, such as the positively supercoiled or relaxed DNA. These findings not only provide a simple mechanism for locally sensing the DNA topology but also lead to the prediction that, due to their different tertiary intra-molecular interactions, supercoiled molecules of opposite signs must display markedly different physical properties. Sticky inter-segmental interactions in positively supercoiled or relaxed DNA are expected to greatly slow down the slithering dynamics of DNA. We therefore suggest that the intrinsic helical chirality of DNA may have oriented the early evolutionary choices for DNA topology.
10.1371/journal.pone.0009326
pubmed_631_15253
Ubiquitin and ubiquitin-like proteins (Ubls), such as SUMO, are covalently conjugated to their targets by related, but distinct enzymatic conjugation reactions that involve the dynamic E1-E2-E3 enzyme cascade. E1s activate Ubls by catalyzing Ubl C-terminal adenylation, with the help of ATP, to form a covalent thioester bond. Subsequently, Ubls are transferred to E2 to generate a thioester-linked product. In previous studies, we showed the dynamic processes and thioester intermediates of SUMO with its E1 and E2 conjugating enzymes. Studies of the enzyme specificity of the Ubl conjugation cascade are normally carried out by tedious biochemical processes, and the reaction intermediates are often difficult to capture because they are unstable and have short half-lives. Here, using our recently developed robust quantitative FRET-based technology, we describe systematic investigations of enzymatic specificity and thioester intermediate determination of ubiquitin with its E1-E2 ligases in conjugation with SUMO and its ligases. Our technology easily determined the strong specificity of enzyme-substrate interactions and thioester intermediates in ubiquitination and SUMOylation cascades. The traditional FRET pair ECFP/EYFP lacked adequate signals for these assays. However, in contrast, the highly sensitive FRET pair CyPet/YPet was easily harnessed to define the reaction specificities and intermediates. In addition, the thioester intermediates can be readily monitored by a newly defined FRET index parameter. These results provide an example of a systems biology approach to determine Ubl conjugation specificity and demonstrate that a robust FRET technology can be used to identify enzymes and substrates in other Ubl pathways.
10.1039/c3mb70155g
pubmed_1110_21176
Protein SUMOylation has been reported to play a role in innate immune response, but the enzymes, substrates, and consequences of the specific inflammatory signaling events are largely unknown. Reactive oxygen species (ROS) are abundantly produced during macrophage activation and required for Toll-like receptor 4 (TLR4)-mediated inflammatory signaling. Previously, we demonstrated that SENP3 is a redox-sensitive SUMO2/3 protease. To explore any links between reversible SUMOylation and ROS-related inflammatory signaling in macrophage activation, we generated mice with Senp3 conditional knock-out in myeloid cells. In bacterial lipopolysaccharide (LPS)-induced in vitro and in vivo inflammation models, we found that SENP3 deficiency markedly compromises the activation of TLR4 inflammatory signaling and the production of proinflammatory cytokines in macrophages exposed to LPS. Moreover, Senp3 conditional knock-out mice were significantly less susceptible to septic shock. Of note, SENP3 deficiency was associated with impairment in JNK phosphorylation. We found that MKK7, which selectively phosphorylates JNK, is a SENP3 substrate and that SENP3-mediated deSUMOylation of MKK7 may favor its binding to JNK. Importantly, ROS-dependent SENP3 accumulation and MKK7 deSUMOylation rapidly occurred after LPS stimulation. In conclusion, our findings indicate that SENP3 potentiates LPS-induced TLR4 signaling via deSUMOylation of MKK7 leading to enhancement in JNK phosphorylation and the downstream events. Therefore this work provides novel mechanistic insights into redox regulation of innate immune responses.
10.1074/jbc.M117.816769
pubmed_1067_3262
Sixteen infants were analyzed longitudinally from the onset of independent walking to 3 years of age using time parameters, speed and energy recovery. Considerable variation and irregularities were observed in many parameters of infant walking, especially until 13 months of age when infants had difficulty in walking steadily step by step. Infant walking until 3 years of age was characterized by a small braking duration, caused mainly by the forward inclination of the trunk, a large relative stance phase duration, which maintained static balance, short stride length, due to the small range of the lower limb joint angle, and a small recovery of external energy. These characteristics were also predominantly evident until 13 months of age. The small recovery characteristic of infants was caused by flexed lower limb joints, pronounced irregularities in energy output, and in younger infants, slow speed. The maximum recovery up until 2 years of age, though smaller than in adults, appeared at about 0.45 dimensionless speed, which is about the same speed that adults in particular naturally and at which their maximum recovery appeared. The forward inclination of the trunk and the lower limb joint angle, influenced the development of many characteristics of bipedal walking.
10.1016/j.gaitpost.2004.09.005
pubmed_997_8812
BACKGROUND Cuproptosis, a newly discovered mode of cell death, has been less studied in hepatocellular carcinoma (HCC). Exploring the molecular characteristics of different subtypes of HCC based on cuproptosis-related genes (CRGs) is meaningful to HCC. In addition, immunotherapy plays a pivotal role in treating HCC. Exploring the sensitivity of immunotherapy and building predictive models are critical for HCC. METHODS The 357 HCC samples from the TCGA database were classified into three subtypes, Cluster 1, Cluster 2, and Cluster 3, based on the expression levels of ten CRGs genes using consensus clustering. Six machine learning algorithms were used to build models that identified the three subtypes. The molecular features of the three subtypes were analyzed and compared from some perspectives. Moreover, based on the differentially expressed genes (DEGs) between Cluster 1 and Cluster 3, a prognostic scoring model was constructed using LASSO regression and Cox regression, and the scoring model was used to predict the efficacy of immunotherapy in the IMvigor210 cohort. RESULTS Cluster 3 had the worst overall survival compared to Cluster 1 and Cluster 2 (P = 0.0048). The AUC of the Catboost model used to identify Cluster 3 was 0.959. Cluster 3 was significantly different from the other two subtypes in gene mutation, tumor mutation burden, tumor microenvironment, the expression of immune checkpoint inhibitor genes and N6-methyladenosine regulatory genes, and the sensitivity to sorafenib. We believe Cluster 3 is more sensitive to immunotherapy from the above analysis results. Therefore, based on the DEGs between Cluster 1 and Cluster 3, we obtained a 7-gene scoring prognostic model, which achieved meaningful results in predicting immunotherapy efficacy in the IMvigor210 cohort (P = 0.013). CONCLUSIONS Our study provides new ideas for molecular characterization and immunotherapy of HCC from machine learning and bioinformatics. Moreover, we successfully constructed a prognostic model of immunotherapy.
10.1186/s12859-022-04997-0
pubmed_416_15710
Two new dimeric sesquiterpenoids and a new trimeric drimane sesquiterpenoid named cinnafragrins A-C (1-3), together with cinnamodial (4), D-mannitol, capsicodendrin (5), and a vitamin E analogue, delta-tocotrienol, were isolated from Cinnamosma fragrans, a Malagasy medicinal plant. The structures of the new compounds were determined on the basis of physical, chemical, and spectroscopic evidence. Capsicodendrin, previously isolated from Capsicodendron dinisii and tentatively suggested to be a tetramer of cinnamodial, was revised structurally as a mixture of C-12'-epimers of 12'-hydroxycinnafragrin B by extensive 2D NMR analysis and X-ray crystallography of the lactone derivative, cinnafragrolide (6). The chemosystematics of the family Canellaceae are discussed.
10.1021/np0601298
pubmed_387_2002
Idiopathic osteonecrosis of the femoral head presents many problems of diagnosis and treatment during the early stages of the disease due to the paucity of clinical manifestations and the absence of radiographic evidence. By the time that the radiographic and clinical evidence are sufficient for a reliable diagnosis, the disease is so advanced that treatment is a problem. Early diagnosis is therefore the key issue and, in this context, instrumental tests, CT scanning and the measurement of blood flow velocity play an ever-increasing role. In the early stages of the disease CT scanning shows characteristic changes in the socalled "asterisk sign" of Dihlmann, and this has proved useful not only in terms of diagnosis, but also in order to initiate early treatment of the disease. Although radioisotope methods with double tracer do not allow for direct visualisation of the circulation in the femoral head, they have proved to be extremely reliable in evaluating the perfusion index of the femoral heads by providing activity/time curves which are a reliable estimate of regional blood flow.
pubmed_387_2002
pubmed_917_4598
Four different porous-coated tibial prosthetic implants were tested for their mechanical stability following implantation into paired cadaver tibias: Porous Coated Anatomic (PCA), Miller-Galante, Whiteside, and Anatomic Modular Knee (AMK). Following implantation the test sample was loaded eccentrically over the medial tibial plateau at 40 cycles per minute for 300,000 cycles, using an MTS machine. This represents the number of steps taken by the average person in a six- to 12-month period. Load varied sinusoidally from 5 to 115 kg. Subsidence and lift-off of the tibial plate from its bony bed was recorded for each implant, using linear variable differential transformers. The greatest degree of mechanical stability was observed with the AMK design, which is secured to the bone bed using four peripherally placed 6.5-mm cancellous screws. No motion in excess of 100 micron was observed. The central-stemmed Whiteside design and the cortical screw fixated Miller-Galante designs provided slightly less stability, each demonstrating approximately 200 micron of lift-off on the unweighted side. The PCA design exhibited the greatest amount of micromotion with subsidence and lift-off displacements of 500 micron (0.5 mm).
pubmed_917_4598
pubmed_520_9976
Cannulation of the internal jugular vein is often necessary for the management of critically ill patients. Despite being a very common procedure and performed more and more safely, several complications still occur. Horner's Syndrome (HS) is one of those complications described before the use of ultrasound as a method of guidance. HS is caused by functional interruption of sympathetic nerve supply to the eye, leading to a classic triad of ipsilateral ptosis, miosis, and anhidrosis. We present the case of a patient, in need of emergent surgery to control the hemorrhagic focus after delivery, with a transient HS secondary to internal jugular vein cannulation under real-time ultrasound guidance.
10.7759/cureus.28700
pubmed_491_24630
OBJECTIVE The aim of this work was to determine the prevalence and progression of epilepsy in adult patients with mitochondrial disease. METHODS We prospectively recruited a cohort of 182 consecutive adult patients attending a specialized mitochondrial disease clinic in Newcastle upon Tyne between January 1, 2005 and January 1, 2008. We then followed this cohort over a 7-year period, recording primary outcome measures of occurrence of first seizure, status epilepticus, stroke-like episode, and death. RESULTS Overall prevalence of epilepsy in the cohort was 23.1%. Mean age of epilepsy onset was 29.4 years. Prevalence varied widely between genotypes, with several genotypes having no cases of epilepsy, a prevalence of 34.9% in the most common genotype (m.3243A>G mutation), and 92.3% in the m.8344A>G mutation. Among the cohort as a whole, focal seizures, with or without progression to bilateral convulsive seizures, was the most common seizure type. Conversely, all of the patients with the m.8344A>G mutation and epilepsy experienced myoclonic seizures. Patients with the m.3243A>G mutation remain at high risk of developing stroke-like episodes (1.16% per year). However, although the standardized mortality ratio for the entire cohort was high (2.86), this ratio did not differ significantly between patients with epilepsy (2.96) and those without (2.83). INTERPRETATION Epilepsy is a common manifestation of mitochondrial disease. It develops early in the disease and, in the case of the m.3243A>G mutation, often presents in the context of a stroke-like episode or status epilepticus. However, epilepsy does not itself appear to contribute to the increased mortality in mitochondrial disease.
10.1002/ana.24525
pubmed_665_17320
BACKGROUND & AIMS In 2003, a sharp increase in cases of lymphogranuloma venereum (LGV) caused by Chlamydia trachomatis in men who have sex with men was reported in Europe and, recently, cases of LGV have been reported in North America. METHODS We reviewed 3 cases of LGV proctitis recently diagnosed in Canada. RESULTS All 3 cases occurred in men who had sex with men; 2 of the patients had human immunodeficiency virus infection and 1 subsequently seroconverted. A delay in diagnosis occurred in all 3 patients: 2 patients were misdiagnosed initially with inflammatory bowel disease and 1 patient was treated as a case of non-LGV C trachomatis. CONCLUSIONS Given the recent outbreak, gastroenterologists in Europe and North America need to be familiar with the diagnosis and treatment of LGV because it mimics inflammatory bowel disease endoscopically and histologically.
10.1016/j.cgh.2005.12.006
pubmed_440_14421
A novel software, Pinnacle was used to reassess the reproducibility of a 2-step lectin-based O-glycopeptide enrichment method. A publicly available dataset consisting of 12 data files representing 3 technical replicates of enriched glycopeptides from human serum was investigated. Previously, an attempt for reproducibility assessment was made utilizing an MS/MS scan (MS2)-based method. However, the stochastic nature of precursor ion selection strongly biased this approach leading to underestimated rate of reproducibility. To bypass this problem, our present method follows the general path to confidently identify O-glycopeptides (database search with MS/MS data) supplemented with full scan/survey scan (MS1)/extracted ion chromatogram (XIC) mining in all files using two software packages, Pinnacle and Skyline. Confident MS/MS identifications were delivered by Protein Prospector. With this input Skyline indicated a 70% reproducibility for our workflow. However, Pinnacle performed better, indicating the presence of 90% of the confidently assigned glycopeptides in all the three replicates. Pinnacle, just like Skyline, performs ion extraction using the high accuracy, high resolution mass measurement data but it also utilizes all the available MS/MS spectra, even from different activation methods, within the same file to make mass spectrometric data evaluation for glycopeptides more reliable.
10.1002/elps.201800223
pubmed_968_21597
This study investigated the effect of three commercial calcium silicate-based materials (CSBM) on cytotoxicity and pro-and anti-inflammatory cytokines production in cultured human periodontal ligament stem cells (hPDLSCs). Culture of hPDLSCs was established and characterized. Extracts of Bio-C Sealer (Angelus, Londrina, PR, Brazil), MTA Fillapex (Angelus, Londrina, PR, Brazil) and PBS Cimmo HP (Cimmo Soluções em Saúde, Pouso Alegre, MG, Brazil) were prepared by placing cement specimens (5 x 3 mm) in culture medium. Then, the extracts were serially two-fold diluted (1, 1:2, 1:4, 1:8, 1:16) and inserted into the cell-seeded wells for 24, 48 and 72 h for MTT assays. TNF-α and IL-10 cytokines were quantified by ELISA at 24h-cell supernatants. Data were analyzed by ANOVA and Tukey's test (α = 0.05). All CSBM exhibited some cytotoxicity that varied according to extract concentration and time of evaluation. MTA Fillapex presented the highest cytotoxic effects with significant reduction of metabolic activity/cell viability when compared to Bio-C Sealer and Cimmo HP®. TNF-α was significantly upregulated by the three tested cements (p < 0.05) while only MTA Fillapex significantly upregulated IL-10 in comparison to control. Taken collectively, the results showed that PBS Cimmo HP®, Bio-C Sealer and MTA Fillapex present mild and transient cytotoxicity and slightly induced TNF-α production. MTA Fillapex upregulated IL-10 release by hPDLSCs.
10.1590/0103-6440202104467
pubmed_1085_2699
Techniques for repairing focal articular cartilage defects are evolving from methods that induce a local stimulation of fibrocartilaginous repair to methods that will lead to a hyaline articular cartilage repair. Mosaicplasty and autologous chondrocyte implantation are examples of the latter. A tissue engineered hyaline cartilage implant that could be used off the self would minimize the morbidity of these techniques. However, there are significant questions that still need to be resolved before such tissue-engineered implants will be practical. Principally among these is the question of what is the ideal matrix for such an implant, particularly from the standpoint of the best material and architecture. Second, what is the ideal cell source to use with these implants. A third major unknown is what is the most ideal way to use growth factors to enhance the repair. As these issues are resolved, the prospects of a tissue engineered cartilage replacement will advance from theory to practice.
10.1097/00003086-200110001-00025
pubmed_432_2336
The skeletochronological analysis of 34 adult lizards from population of Acanthodactylus pardalis of Kerkennah islands in Tunisia enabled to: determine the individual age of the animals; delineate four various cohorts making up the studied population; evaluate around 4 years life span in nature of this species; point out that the renewal rate accounts for 41% of its population. Moreover the method of "maximums successifs" is applied on sizeable sample in order to shore up the obtained results.
pubmed_432_2336
pubmed_733_19697
Cuticular hydrocarbons of an ectoparasitic wasp attacking two beetle hosts have been identified and examined for the influence of age, gender, mating status, and host on hydrocarbon composition. The 37 wasp hydrocarbons identified consisted of a series of n-alkanes (C16 to C33), 3-, 5-, 9-, 10-, 11-, and 12-methyl alkanes and a series of Z-7 and Z-9 monoenes (C23:1 to C27:1). One C25:2 diene was found. No effects of hydrocarbon composition as a function of age, gender, or mating status were found for the wasps. Wasps reared on Hypothenemus hampei, however, had 12/37 significant abundance differences to those reared on Caulophilus oryzae, although all but one of these differences were for components in less than 2% relative abundance. The C25:2 diene from wasps reared on H. hampei was present in about 10% whereas from wasps reared on C. oryzae it was present in about 2%. The hydrocarbons of one host for this wasp, the coffee berry borer (Coleoptera: Scolytidae), have been previously reported [Howard and Infante, Ann. Entomol. Soc. Am. 89:700-709 (1996)]. The hydrocarbons of the alternative host, C. oryzae (Coleoptera: Curculionidae) consists of n-alkanes (C17 to C31), 3-, 4-, 5-, 7-, 9-, 11-, 12-, 13-, 14-, and 15-methyl alkanes, and a series of dimethyl alkanes of the series 3, 17-; 5, 11-; 5, 17-; 7, 11-; 7, 13-; 13, 17-; and 15, 19-. No unsaturated hydrocarbons were found. No significant differences in hydrocarbon composition were found between male and female C. oryzae. Hydrocarbon patterns of four species of Cephalonomia are compared and shown to be species-specific. The data are discussed in terms of ecological and physiological parameters.
10.1002/arch.10034
pubmed_639_18309
BACKGROUND Conflicting statements by stakeholders in obstetric care have suggested different criteria for defining peripartum fever and suspected intraamniotic infection, which have not been evaluated. METHODS A case-control study of pregnancies between 35 and 41 weeks at a single tertiary care center between January 2016 and December 2017. Cases with pathology-confirmed chorioamnionitis were identified, and demographic data, risk factors, and neonatal outcomes were extracted from the medical record. The American College of Gynecology (ACOG) and National Institutes of Health (NIH) Workshop guidelines for identifying isolated maternal fever and suspected intraamniotic infection were applied, retrospectively. Odds ratios, sensitivity/specificity, and predictive value of each guideline for pathology-confirmed chorioamnionitis and for secondary outcomes of interest were determined. RESULTS 943 mother-infant dyads were evaluated including 41 (4.3%) with pathology-confirmed chorioamnionitis. Among cases, 18 (43.9%) experienced any maternal temperature ≥38°C (100.4°F) with 12 (29.2%) and 8 (19.5%) cases meeting criteria for isolated maternal fever according to the ACOG and Workshop guidelines, respectively. Furthermore, the ACOG and Workshop guidelines correctly identified 6 (14.6%) and 3 (7.3%) of cases of pathology-confirmed chorioamnionitis with high agreement between definitions (κ = 0.63). Laboratory evaluation, antimicrobial exposure, and prolonged length of stay in offspring are substantially higher in cases as compared to controls. CONCLUSIONS Guidelines that rely on maternal fever definitions for the diagnosis of suspected intraamniotic infection exhibit high agreement with low sensitivity, but high specificity and negative predictive value for pathology-confirmed chorioamnionitis. Maternal temperature ≥38°C continues to drive clinical decision-making for both mother and offspring.
10.1111/birt.12548
pubmed_691_16936
Because many or most lipid-laden foam cells in atheromas and in xanthomas derive from macrophages, it is important to understand how they accumulate lipids and how they can divest themselves of lipids. The mobilization of stored triglycerides from macrophages was studied in cell cultures. Mouse resident peritoneal macrophages and J774 macrophages increased their triglyceride content six- to tenfold during a 24-hour incubation with free fatty acids complexed to albumin. Subsequent incubation in fresh medium containing free fatty acid-poor albumin was accompanied by a fall in cell triglyceride content (50% in 20 hours) and a corresponding increase in medium-free fatty acid. Release of free fatty acid was linear as a function of time, provided fresh medium was added hourly. When medium was not changed, release rates fell off rapidly, probably due to re-uptake of released free fatty acid. Chloroquine did not affect the rate of free fatty acid release. The results suggest that macrophages-foam cells can reduce their triglyceride stores via the action of a nonlysosomal (presumably cytoplasmic) neutral triglyceride lipase.
10.1161/01.atv.4.6.630
pubmed_747_2179
A study of 259 clinical isolates of gentamicin-resistant Gram-negative bacili (GRNB) has revealed 99,2% crossresistance with tobramycin and 6,9% with amikacin. Resistance to all 3 drugs is transferable in vitro. Simultaneous transfer of resistance to ampicillin, carbenicillin, cephalothin, tetracycline, chloramphenicol, sulphonamides, co-trimoxazole, streptomycin and kanamycin was shown to occur, emphasizing the potential for the selection of aminoglycoside-resistant organisms by the use of many other drugs. All GRNB studied were multiresistant. While amikacin should prove useful for those infections caused by GRNB which require treatment, care should be exercised in its use, to minimize the emergence of large-scale amikacin resistance.
pubmed_747_2179
pubmed_1115_5455
OBJECTIVE To retrospectively evaluate the role of video-urodynamics (VUD) in the diagnosis and management of voiding dysfunction in children. PATIENTS AND METHODS The records of the 128 children with dysfunctional voiding symptoms were retrospectively evaluated. All patients had a noninvasive screening assessment consisting of a detailed voiding history, ultrasonography and uroflowmetry, and measurement of residual urine. All the patients had also undergone VUD with no selection criteria. The results of VUD were compared retrospectively with the noninvasive screening assessment results. RESULTS In 84 patients with urge syndrome VUD showed detrusor overactivity in 72 (86%); the bladder configuration and voiding-phase results were normal. Three (3.5%) patients had low-grade reflux. In 38 patients with voiding dysfunction VUD showed an intermittent flow pattern and/or increased electromyographic activity with a "spinning top" deformity of the bladder neck and increased detrusor pressure during voiding. Five (13%) of these children had low-grade reflux. In six infrequent voiders VUD revealed increased bladder capacity with fractionated flow patterns, with concomitantly increased abdominal pressures. There was decreased detrusor pressure during voiding with significant residual urine volume in only two patients; there was no reflux in any of the patients in this group. CONCLUSION We do not recommend routine VUD in children with non-neurogenic voiding dysfunction, as it does not generally change the management and treatment. A detailed voiding history and physical examination is usually sufficient for a correct diagnosis.
10.1111/j.1464-410X.2003.04734.x
pubmed_468_3039
Disturbances in static balance have been demonstrated in subjects with persistent whiplash. Some also report loss of balance and falls. These disturbances may contribute to difficulties in dynamic tasks. The aim of this study was to determine whether subjects with whiplash had deficits in dynamic and functional balance tasks when compared to a healthy control group. Twenty subjects with persistent pain following a whiplash injury and twenty healthy controls were assessed in single leg stance with eyes open and closed, the step test, Fukuda stepping test, tandem walk on a firm and soft surface, Singleton test with eyes open and closed, a stair walking test and the timed 10 m walk with and without head movement. Subjects with whiplash demonstrated significant deficits (p < 0.01) in single leg stance with eyes closed, the step test, tandem walk on a firm and soft surface, stair walking and the timed 10 m walk with and without head movement when compared to the control subjects. Specific assessment and rehabilitation directed towards improving these deficits may need to be considered in the management of patients with persistent whiplash if these results are confirmed in a larger cohort.
10.1016/j.math.2011.01.012
pubmed_71_3983
To mimic the natural extracellular matrix (ECM) and to facilitate tissue regeneration, in-situ formable collagen/hyaluronan composite hydrogels were prepared by a facile approach via Michael addition reaction, with maleilated collagen (Col-MA) and thiol derivatized hyaluronan (HA-SH). The hydrogels were denoted as CHG-1, CHG-2, CHG-3 and CHG-4 by vinyl/free thiol molar ratio (f) of 1:1, 1:2, 1:3 and 1:4, respectively. Results showed that with decrease of the f values, the gelation time decreased from 43s to 15s, Young's modulus increased from 1671.65Pa to 9105.86Pa, and the swelling ratio increased from 1.5 to 12.7. SEM images of the air-dried samples revealed that the chemical modification process did not denature the collagen, and the interwoven collagen fibrils were indeed observed. Cell culture confirmed that the CHG facilitated the growth and proliferation of MC3T3-E1. Cells displayed spreading morphology and formed nearly aligned cell layers with the extension of culture time. Therefore, it is suggested that CHG can be used as injectable materials for tissue regeneration.
10.1016/j.msec.2017.04.046
pubmed_24_7825
Geranyl nitrile (GN) and citronellyl nitrile (CN) are fragrance components used in consumer and personal care products. Differences in the clastogenicity of these two terpenes are postulated to result from differential biotransformation, presumably involving the conjugated nitrile moiety. The metabolic clearance and biotransformation of GN and CN were compared in primary hepatocytes from mice, rats, and humans. For determination of intrinsic clearance, GN and CN were incubated with hepatocytes in sealed vials, and the headspace was sampled periodically by solid-phase microextraction and analyzed by gas chromatography/mass spectrometry. For metabolite identification, GN and CN were incubated with hepatocytes from each species for 60 min, and reaction mixtures were extracted and analyzed by mass spectroscopy. Both GN and CN were rapidly metabolized in hepatocytes from all species (T1/2, 0.7-11.6 min). Within a species, intrinsic clearance was similar for both compounds and increased in the order human < rat << mouse. Major common pathways for biotransformation of GN and CN involved 1) epoxidation of the 6-alkenyl moiety followed by conjugation with glutathione, 2) hydroxylation of the terminal methyl group(s) followed by direct conjugation with glucuronic acid in rodents or further oxidation to the corresponding acid in human cells, and 3) hydroxylation of the allylic C5 position. No evidence for either phase I or phase II metabolism of the conjugated nitrile moiety was obtained. Thus, the presumed metabolic basis for differences in genotoxicity remains elusive.
10.1124/dmd.105.005496
pubmed_612_17338
Objective. To evaluate fidelity to the comprehensive medication management (CMM) framework in a patient care skills course by using CMM essential functions to analyze the domains of content and competency.Methods. A mixed methods approach was used to compare the curriculum of the Pharmacist's Patient Care Process II skills course to the nationally developed CMM framework. The content of the course curriculum was mapped to the CMM framework and the percentage of omissions and deficiencies were calculated. Student competency was analyzed using pharmacy students' assessment scores.Results. Of the 102 class hours in the PPCP II course, 41.5 hours (40.7%) were spent teaching CMM content. Deficiencies in and omissions of content from the CMM framework were calculated at 14.3%, indicating an overall alignment with the CMM framework of 71.4%. For the competency domain, the percentage of students initially achieving competence ranged from 76.6% to 98.7% on formative assessments in 2018-2019 and 2019-2020, combined academic years. For the summative assessment, 87.5% in 2018-2019 and 69.2% in 2019-2020 achieved competency on their first attempt, with levels rising significantly to 98.8% and 98.7%, respectively, after remediation. Overall, 98.7% of students achieved competency in CMM-related course curriculum.Conclusion. About 70% of the CMM framework for the core domain of content can be covered in approximately 40 hours of direct curricular time, and the majority of students can achieve competency. The omissions of and deficiencies in CMM content identified in this study highlight opportunities for course improvement. Remediation of students with deficient skills resulted in a significant improvement in the percentage of students achieving competence in CMM.
10.5688/ajpe8565
pubmed_164_2912
PURPOSE OF REVIEW Endoscopic enucleation of the prostate is the most advanced form of surgical management of benign prostate hyperplasia. The purpose of this review is to update the reader on various modalities currently in use, and in trial, for endoscopic enucleation. RECENT FINDINGS A recent paradigm shift has occurred for the proponents of electrosurgery technology to utilizes the advantages offered by laser enucleation with interest in bipolar enucleation. Holmium laser enucleation still has the greatest randomized evidence with the longest follow-up among all the various lasers used to perform enucleation. SUMMARY Randomized trials with longer follow-up are required to demonstrate whether nonholmium types of energy really have advantages in enucleation (speed, ease of use and hemostasis) and durability (decade plus) as compared to the holmium laser.
10.1097/MOU.0000000000000005
pubmed_892_12515
In guinea-pigs, myocarditis was induced under experimental conditions by immunizing the animals with rabbit skeletal muscle myosin-beta. The salient histopathological features were foci of perivascular lymphonononuclear aggregates, necrosis, and degeneration of myocardial cells. Antimyosin-beta antibodies in the immune complexes were demonstrated in the sera of the guinea-pigs. An immune-complex-mediated tissue-injury is proposed in the pathogenesis of myocarditis.
pubmed_892_12515
pubmed_893_23204
Staphylococcus aureus (S. aureus) is one of the most frequently isolated pathogens in neonatal cases of early and late-onset sepsis. Drug resistance profiles and carriage of toxin genes may affect the treatment and outcome of an infection. The present study aimed to determine the antimicrobial resistance patterns and frequencies of the toxin-associated genes conserved virulence factor B (CvfB), staphylococcal enterotoxin Q (SEQ) and staphylococcal enterotoxin K (SEK) among S. aureus isolates recovered from paediatric patients with bloodstream infections (BSIs) in Guangzhou (China). Of the 53 isolates, 43.4% were methicillin-resistant S. aureus (MRSA), and resistance rates to penicillin, erythromycin, clindamycin, trimethoprim/sulfamethoxazole, tetracycline, and ciprofloxacin of 92.5, 66.0, 62.3, 13.2, 20.8 and 1.9% were recorded, respectively. However, no resistance to nitrofurantoin, dalfopristin/quinupristin, rifampicin, gentamicin, linezolid or vancomycin was detected. Resistance to erythromycin, clindamycin and tetracycline in the MRSA group was significantly higher than that in the methicillin-susceptible S. aureus (MSSA) group. No significant differences in antimicrobial resistance patterns were noted between two age groups (≤1 year and >1 year). The proportion of S. aureus isolates positive for CvfB, SEQ and SEK was 100, 34.0 and 35.8%, respectively, with 24.5% (13/53) of strains carrying all three genes. Compared with those in MSSA isolates, the rates of SEK, SEQ and SEK + SEQ carriage among MRSA isolates were significantly higher. Correlations were identified between the carriage of SEQ, SEK and SEQ + SEK genes and MRSA (contingency coefficient 0.500, 0.416, 0.546, respectively; P<0.01). In conclusion, MRSA isolated from the blood of paediatric patients with BSIs not only exhibited higher rates of antimicrobial resistance than MSSA from the same source, but also more frequently harboured SEK and SEQ genes. The combination of the two aspects influenced the dissemination of MRSA among children. The present study clarified the characteristics of BSI-associated S. aureus and enhanced the current understanding of the pathogenicity and treatment of MRSA.
10.3892/etm.2017.5199
pubmed_912_10463
Primary cilia are present on almost all vertebrate cells, and they have diverse functions in distinct tissues. Cilia are important for sensation in multiple capacities in contexts as different as the retina, kidney, and inner ear. In addition to these roles, cilia play a critical part in various developmental processes. Of particular importance is the development of the neural tube, where cilia are essential for the transduction of the Sonic Hedgehog (Shh) signaling pathway that specifies neuronal cell fates. This relationship is well established and is the most recognizable function for cilia in the neural tube, but it may be part of a larger picture. Here, we discuss the links between cilia and Shh signaling, as well as suggesting additional roles for cilia, and mechanisms for their placement, in the neural tube.
10.1186/2046-2530-1-19
pubmed_425_1840
DNA mutations govern cancer development. Cancer mutation profiles vary dramatically among the individuals. In some cases, they may serve as the predictors of disease progression and response to therapies. However, the biomarker potential of cancer mutations can be dramatically (several orders of magnitude) enhanced by applying molecular pathway-based approach. We developed Oncobox system for calculation of pathway instability (PI) values for the molecular pathways that are aggregated mutation frequencies of the pathway members normalized on gene lengths and on number of genes in the pathway. PI scores can be effective biomarkers in different types of comparisons, for example, as the cancer type biomarkers and as the predictors of tumor response to target therapies. The latter option is implemented using mutation drug score (MDS) values, which algorithmically rank the drugs capacity of interfering with the mutated molecular pathways. Here, describe the mathematical basis and algorithms for PI and MDS values calculation, validation and implementation. The example analysis is provided encompassing 5956 human tumor mutation profiles of 15 cancer types from The Cancer Genome Atlas (TCGA) project, that totally make 2,316,670 mutations in 19,872 genes and 1748 molecular pathways, thus enabling ranking of 128 clinically approved target drugs. Our results evidence that the Oncobox PI and MDS approaches are highly useful for basic and applied aspects of molecular oncology and pharmacology research.
10.1007/978-1-0716-0138-9_16
pubmed_78_11082
Sleep, a basic physiological need of all humans, appears to be both integrative and restorative. However, studies have reported that 33-51% of women show a dramatic increase in sleep disturbance in the mid-life years, a time when they enter menopause. The purposes of this study were to (1) explore the prevalence of poor sleep quality in menopausal women; (2) identify the relationship between sleep quality of menopausal women and its related factors; (3) predict the possible explanations of how the related variables affect sleep quality of menopausal women; and (4) provide recommendations for future strategies that aim to improve sleep quality of menopausal women. A cross-sectional, correlation coefficient design was used. Purposive sampling was employed to recruit 197 menopause women from a small town in central Taiwan. T-test, one-way ANOVA, and multiple regression were used for data analysis. The results were as follows: (1) overall, the total score for sleep quality was 5.55 +/- 3.47; 57.9% of subjects were identified as good sleepers and 42.1% as poor sleepers; (2) there were significant differences in quality of sleep related to occupational situation, history of chronic disease, menopausal status, number of chronic diseases, and number of menopausal symptoms (t = - 3.49, - 3.37, p < .01; F = 3.62, p < .05, F = 4.95, 5.35, p < .01); (3) depression and aging were strongly related to quality of sleep (r = .57; .22, p < .01); (4) 36% of variance in quality of sleep can be explained by depression and aging.
10.1097/01.jnr.0000387536.60760.4e
pubmed_489_23633
Ghrelin levels are suppressed in obese subjects and subjects with Type 2 diabetes mellitus (T2DM). Exercise-stimulated decreases in plasma ghrelin are a proposed mediator of exercise-induced satiety in healthy subjects. However, exercise-induced satiety and the impact of impaired ghrelin levels in obesity-related disease are poorly understood. Therefore our objective was to investigate exercise-induced postprandial satiety and ghrelin responses in overweight subjects with T2DM (N = 8) and healthy controls (N = 7). Visual analog scale satiety questionnaires (assessing hunger, thirst, food that could be eaten, nausea, and fullness) and circulating levels of glucose, insulin, and total and acylated ghrelin were measured at baseline and in response to a 75 g oral glucose load, provided immediately after an aerobic exercise bout (1 h at 50% Wmax) or no exercise (rest trial), on two separate occasions. Baseline levels of total (284.4 ± 15.9 and 397.6 ± 35.2 pmol/l) and acylated ghrelin (7.9 ± 1.0 and 13.7 ± 1.2 pmol/l) were lower in subjects with T2DM compared with healthy subjects (P < 0.05). In the rest trial, post- vs. preprandial feeling of fullness increased in healthy subjects but decreased in subjects with T2DM (healthy vs. T2DM; P < 0.05). Exercise increased postprandial fullness in the T2DM group (P < 0.05), while plasma ghrelin levels were unaffected. Our data suggest that the presence of T2DM likely drives suppressed ghrelin levels and poor appetite regulation, but a single exercise bout is sufficient to restore oral glucose-induced fullness independently of ghrelin.
10.1152/japplphysiol.00204.2013
pubmed_830_20674
Bisphosphonates are widely used in the treatment of osteoporosis to reduce fracture risk. Because of their long retention time in bone and uncommon side effects, questions have been raised about the optimal duration of therapy. Potential side effects appear to be rare and may not be causally related. Although there is no strong science to guide "drug holidays," there appears to be some lingering antifracture benefit when treatment is stopped, so some time off treatment should be offered to most patients on long-term bisphosphonate therapy. For most patients with osteoporosis, the benefits of treatment outweigh the risks.
10.1016/j.ecl.2012.04.007
pubmed_880_18802
PURPOSE Chronic myeloid leukemia (CML) management changed dramatically with the development of imatinib mesylate (IM), the first tyrosine kinase inhibitor targeting the BCR-ABL1 oncoprotein. In Sweden, the drug was approved in November 2001. We report relative survival (RS) of patients with CML diagnosed during a 36-year period. PATIENTS AND METHODS Using data from the population-based Swedish Cancer Registry and population life tables, we estimated RS for all patients diagnosed with CML from 1973 to 2008 (n = 3173; 1796 males and 1377 females; median age, 62 years). Patients were categorized into five age groups and five calendar periods, the last being 2001 to 2008. Information on use of upfront IM was collected from the Swedish CML registry. RESULTS Relative survival improved with each calendar period, with the greatest improvement between 1994-2000 and 2001-2008. Five-year cumulative relative survival ratios (95% CIs) were 0.21 (0.17 to 0.24) for patients diagnosed 1973-1979, 0.54 (0.50 to 0.58) for 1994-2000, and 0.80 (0.75 to 0.83) for 2001-2008. This improvement was confined to patients younger than 79 years of age. Five-year RSRs for patients diagnosed from 2001 to 2008 were 0.91 (95% CI, 0.85 to 0.94) and 0.25 (95% CI, 0.10 to 0.47) for patients younger than 50 and older than 79 years, respectively. Men had inferior outcome. Upfront overall use of IM increased from 40% (2002) to 84% (2006). Only 18% of patients older than 80 years of age received IM as first-line therapy. CONCLUSION This large population-based study shows a major improvement in outcome of patients with CML up to 79 years of age diagnosed from 2001 to 2008, mainly caused by an increasing use of IM. The elderly still have poorer outcome, partly because of a limited use of IM.
10.1200/JCO.2011.34.7146
pubmed_510_7853
For mouse kidney cells assayed in primary culture, the Do and n values were 1.1 +/- 0.06 Gy and 7 +/- 2 for single cells irradiated in vitro, and 1.3 +/- 0.08 Gy and 25 +/- 11 for in vivo irradiation. The lower radiosensitivity in vivo was shown not to be caused by natural hypoxia, as the average oxygen enhancement ratios were 2.6 +/- 0.3 for in vitro and 2.8 +/- 0.4 for in vivo irradiation. Irradiations of fragments of kidney tubules produced similar survivals as irradiations of kidneys in situ, even for irradiation immediately before the fragments were disaggregated into single cells. The critical point of change in radiosensitivity from in vivo to in vitro values due to this contact effect was the time that the kidney cells were monodispersed.
10.1016/0360-3016(91)90234-u
pubmed_150_14598
There is a large population of patients with end-stage congestive heart failure who cannot be treated by means of conventional cardiac surgery, cardiac transplantation, or chronic catecholamine infusions. Implantable cardiac devices, many designated as destination therapy, have revolutionized patient care and outcomes, although infection and complications related to external power sources or routine battery exchange remain a substantial risk. Complications from repeat battery replacement, power failure, and infections ultimately endanger the original objectives of implantable biomedical device therapy - eliminating the intended patient autonomy, affecting patient quality of life and survival. We sought to review the limitations of current cardiac biomedical device energy sources and discuss the current state and trends of future potential energy sources in pursuit of a lifelong fully implantable biomedical device.
10.1097/MAT.0000000000000412
pubmed_236_14733
The authors describe the case-history of an elderly female patient with an inveterate incarcerated relapsing umbilical hernia. The patient's age, and obviously also associated diseases, were the cause of subjective underrating of the severity of the condition, late admission to hospital and surgical intervention. The syndrome of advanced ileus had already developed as well as local changes complicating or rather making classical surgical treatment impossible. The applied technique which can be described as "no touch" with regard to the hernia and its contents is considered as one of the dominating features of successful treatment. The second dominating feature is a satisfactory interdisciplinary collaboration in treating the condition which at first appeared infaust.
pubmed_236_14733
pubmed_491_15386
Continuous peripheral nerve block (CPNB) success is largely dependent on placement of the catheter close enough to the nerve to allow effective and sustained analgesia following painful surgeries with a minimum volume of local anesthetic. One of the most common problems associated with CPNB involves accurate placement of the catheter tip, migration, and dislodgement of the catheter. This is of increasing importance now that catheters are left in place for prolonged periods of time to provide postoperative analgesia, and patients with peripheral nerve catheters are being discharged home with ambulatory pumps. In response to the challenges of providing safe, effective, and consistently reliable analgesia, research and development in this field is expanding rapidly. This review article presents results from recent publications addressing the subject of peripheral nerve catheter localization.
10.1007/s00540-015-2076-y
pubmed_363_8510
For four decades the oral contraceptive pill has remained popular with young women because of its convenience and effectiveness. There have, however, been continuing concerns about adverse effects. In the 1960s the risk of venous thromboembolism was linked to the dose of estrogen, which was consequently reduced. Later the risks of arterial disease were linked to progestogen dose, which was also reduced. In 1995, three case-control studies linked the risk of venous thromboembolism, not to dose, but to the type of progestogen. Newer 'third-generation' progestogens appeared to carry a higher risk than older formulations. Although the contraceptive pill was already known to increase the risk of venous thromboembolism 3- to 6-fold, and the risks in the three studies were within this range, the public perception was that a new risk had been discovered. In the UK there were two consequences--a rapid change in prescribing patterns and a sharp increase in the abortion rate. Critics suggested that the studies may have been affected by confounding--e.g. by a 'new user' effect and differential prescribing. Views became very polarised. Between 1995 and 2001 second- and third-generation formulations were compared in 16 studies. Thirteen found that third-generation pills carried a higher risk of venous thromboembolism. Editorials and reviews recommended second-generation pills as the first choice for new users but official advice was that third-generation pills could still be prescribed, provided the risks were explained. Rates of thrombosis, per 100,000 women, are five for nonusers, 15 with second-generation pills and 25 for third-generation pills. The increase in mortality rates is around 1 to 2 per million. Drug-industry sponsored studies tended to find lower risks than independent studies and it was assumed that sponsorship produces bias, conscious or unconscious. It is also possible that some 'independent' researchers, motivated by antipathy to multinational pharmaceutical companies, are biased in the opposite way. Compared with the energy put into this debate, other aspects of pill prescribing remain under-researched. For example, doctors on opposite sides of the Atlantic are given different advice about whether gross obesity (a major risk factor for thromboembolism) is a contraindication to oral contraception. Women in developing countries continue to die of pregnancy-related causes and many deaths could be prevented by effective contraception. Rather than bickering, drug manufacturers and academics should be discussing ways of providing the pill to the women who need it most.
10.2165/00002018-200225130-00001
pubmed_723_2486
Hippocampal synaptic dysfunction is a hallmark of Alzheimer's disease (AD). Many agents regulating hippocampal synaptic plasticity show an ameliorative effect on AD pathology, making them potential candidates for AD therapy. In the present study, we investigated spinosin as a regulating agent of synaptic plasticity in AD. Spinosin attenuated amyloid β (Aβ)-induced long-term potentiation (LTP) impairment, and improved plasmin activity and protein level in the hippocampi of 5XFAD mice, a transgenic AD mouse model. Moreover, the effect of spinosin on hippocampal LTP in 5XFAD mice was prevented by 6-aminocaproic acid, a plasmin inhibitor. These results suggest that spinosin improves synaptic function in the AD hippocampus by regulating plasmin activity.
10.4062/biomolther.2019.076
pubmed_378_2292
One-dimensional gold/polyaniline (Au/PANI-CSA) coaxial nanocables with an average diameter of 50-60 nm and lengths of more than 1 mum were successfully synthesized by reacting aniline monomer with chlorauric acid (HAuCl(4)) through a self-assembly process in the presence of D-camphor-10-sulfonic acid (CSA), which acts as both a dopant and surfactant. It was found that the formation probability and the size of the Au/PANI-CSA nanocables depends on the molar ratio of aniline to HAuCl(4) and the concentration of CSA, respectively. A synergistic growth mechanism was proposed to interpret the formation of the Au/PANI-CSA nanocables. The directly measured conductivity of a single gold/polyaniline nanocable was found to be high (approximately 77.2 S cm(-1)). Hollow PANI-CSA nanotubes, with an average diameter of 50-60 nm, were also obtained successfully by dissolving the Au nanowire core of the Au/PANI-CSA nanocables.
10.1002/chem.200501527
pubmed_1019_5050
BACKGROUND Asthma is a complex disease involving gene and environment interactions. Although atopy is a strong predisposing risk factor for asthma, local tissue susceptibilities are required for disease expression. The bronchial epithelium forms the interface with the external environment and is pivotally involved in controlling tissue homeostasis through provision of a physical barrier controlled by tight junction (TJ) complexes. OBJECTIVES To explain the link between environment exposures and airway vulnerability, we hypothesized that epithelial TJs are abnormal in asthma, leading to increased susceptibility to environmental agents. METHODS Localization of TJs in bronchial biopsies and differentiated epithelial cultures was assessed by electron microscopy or immunostaining. Baseline permeability and the effect of cigarette smoke and growth factor were assessed by measurement of transepithelial electrical resistance and passage of fluorescently labeled dextrans. RESULTS By using immunostaining, we found that bronchial biopsies from asthmatic subjects displayed patchy disruption of TJs. In differentiated bronchial epithelial cultures, TJ formation and transepithelial electrical resistance were significantly lower (P < .05) in cultures from asthmatic donors (n = 43) than from normal controls (n = 40) and inversely correlated with macromolecular permeability. Cultures from asthmatic donors were also more sensitive to disruption by cigarette smoke extract. Epidermal growth factor enhanced basal TJ formation in cultures from asthmatic subjects (P < .01) and protected against cigarette smoke-induced barrier disruption (P < .01). CONCLUSIONS Our results show that the bronchial epithelial barrier in asthma is compromised. This defect may facilitate the passage of allergens and other agents into the airway tissue, leading to immune activation and may thus contribute to the end organ expression of asthma.
10.1016/j.jaci.2011.05.038
pubmed_699_21737
OBJECTIVE To evaluate, in-vitro, the change in crown inclination that occurs during orthodontic leveling and alignment using different archwire-bracket-ligation combinations. MATERIALS AND METHODS Four archwire types were tested: (1) 0.012-in stainless steel and (2) 0.0155-in stainless steel multi-stranded, (3) 0.012-in nitinol Orthonol® and (4) 0.012-in nitinol Thermalloy®. Combinations with five types of 0.022-in slot orthodontic brackets were tested: SmartClipTM and Time3® self-ligating brackets, Mini-Taurus® and Victory SeriesTM conventional brackets, and Synergy® conventional-low friction bracket. Conventional brackets were ligated with both stainless steel and elastomeric ligatures. The simulated malocclusion comprised 2.0mm gingival and 2.0mm labial displacements of a maxillary right central incisor. Rotation around the Y-axis (representing labio-palatal inclination) was measured for the different archwire-bracket-ligation combinations. RESULTS The largest rotation was measured whith Orthonol® and Thermalloy® wires when combined with SmartClipTM brackets (8.07±0.24º and 8.06±0.26º, respectively) and with Synergy® brackets ligated with stainless steel ligatures (8.03±0.49º and 8.0±0.37º, respectively). The lower rotation was recorded when Thermalloy®, multi-stranded, and Orthonol® wires were ligated with elastomeric rings to Mini-Taurus® brackets (1.53±0.18º, 1.65± 0.23º and 1.70±0.28º, respectively) and to Victory SeriesTM brackets (1.68± 0.78º, 2.92± 1.40º and 1.74±0.46º, respectively). CONCLUSIONS All archwire-bracket-ligation combinations produced lingual crown inclination; however, lower changes were observed when the conventional brackets were ligated with elastomeric rings. The multi-stranded archwire produced less rotation with nearly every bracket-ligation combination, compared to the other archwires. The effect of the archwire-bracket-ligation combination on tooth inclination during leveling and alignment should be considered during planning treatment mechanics.
10.1590/2177-6709.27.3.e2220489.oar
pubmed_489_15766
The genomic era has enabled the application of molecular tools to the solution of many of the genetic epilepsies, with and without comorbidities. Massively parallel sequencing has recently reinvigorated gene discovery for the monogenic epilepsies. Recurrent and novel copy number variants have given much-needed impetus to the advancement of our understanding of epilepsies with complex inheritance. Superimposed upon that is the phenotypic blurring by presumed genetic modifiers scattering the effects of the primary mutation. The genotype-first approach has uncovered associated syndrome constellations, of which epilepsy is only one of the syndromes. As the molecular genetic basis for the epilepsies unravels, it will increasingly influence the classification and diagnosis of the epilepsies. The ultimate goal of the molecular revolution has to be the design of treatment protocols based on genetic profiles, and cracking the 30% of epilepsies refractory to current medications, but that still lies well into the future. The current focus is on the scientific basis for epilepsy. Understanding its genetic causes and biophysical mechanisms is where we are currently positioned: prizing the causes of epilepsy "out of the shadows" and exposing its underlying mechanisms beyond even the ion-channels.
10.2147/TACG.S7407
pubmed_46_22532
Three transmissible gastroenteritis virus (TGEV) defective RNAs were selected by serial undiluted passage of the PUR46 strain in ST cells. These RNAs of 22, 10.6, and 9.7 kb (DI-A, DI-B, and DI-C, respectively) were detected at passage 30, remained stable upon further passage in cell culture, and significantly interfered with helper mRNA synthesis. RNA analysis from purified virions showed that the three defective RNAs were efficiently packaged. Virions of different densities containing either full-length or defective RNAs were sorted in sucrose gradients, indicating that defective and full-length genomes were independently encapsidated. DI-B and DI-C RNAs were amplified by the reverse transcription-polymerase chain reaction, cloned, and sequenced. DI-B and DI-C genomes are formed by three and four discontinuous regions of the wild-type genome, respectively. DI-C contains 2144 nucleotides (nt) from the 5'-end of the genome, two fragments of 4540 and 2531 nt mostly from gene 1b, and 493 nt from the 3' end of the genome. DI-B and DI-C RNAs include sequences with the pseudoknot motif and encoding the polymerase, metal ion binding, and helicase motifs. DI-B RNA has a structure closely related to DI-C RNA with two main differences: it maintains the entire ORF 1b and shows heterogeneity in the size of the 3' end deletion. This heterogeneity maps at the beginning of the S gene, where other natural TGEV recombination events have been observed, suggesting that either a process of template switching occurs with high frequency at this point or that the derived genomes have a selective advantage.
10.1006/viro.1996.0144
pubmed_34_7030
BACKGROUND AND PURPOSE According to the American Joint Committee on Cancer (AJCC) cancer staging criteria (6th edition), cross-sectional imaging for base of tongue carcinoma is recommended when the deep tissue extent of a primary tumor is in question. The aim of this study was to establish which group of patients MRI might most benefit from accurate clinical staging of base of tongue carcinomas. PATIENTS AND METHODS The clinical stagings of 33 patients with pathologically proven squamous cell carcinomas of the base of tongue were performed by two otorhinolaryngologic surgeons. Their results were compared with the results from MRI interpreted by a neuroradiologist and the numbers of patients being upstaged, downstaged or with an unchanged stage were recorded and analyzed. RESULTS The tumor stages were changed in 13 of 33 patients (39.4%, 95% CI: 23.9-57.87%) and the overall stage groupings were changed in 10 (30.3 %, 95%CI: 15.6-48.7%) after performing MRI. Mis-staging by clinical examination in the overall stage grouping was as high as 83.3% (95%CI: 35.9-99.6%) in stages II and III and 85.7% (95% CI: 42.1-99.6%) in T3. CONCLUSION MRI should be recommended in base of tongue carcinoma whenever clinical examination suggests overall stage groupings II, III or tumor stage T3.
pubmed_34_7030
pubmed_362_7049
Camellia leyeensis Chang & Y. C. Zhong is a plant belonging to the genus Camellia. To determine its correct taxonomic status and better understand its molecular phylogenetic and genetic diversity, we studied the chloroplast genome of this species. Here, we report and characterize the complete chloroplast (cp) genome of C. leyeensis by using Illumina paired-end sequencing data. The chloroplast genome was determined to be 157,063 bp in length with a GC content of 37.30%. The genome contained 136 genes, including 91 protein-coding genes, 37 tRNA genes, and 8 rRNA genes. The sequence contained a large single-copy region (LSC, 86,661 bp), a small single-copy region (SSC, 18,284 bp), and two inverted repeat sequences (IRs, 26,059 bp, each). The GC content of the IR regions (42.96%) was higher than that of the SSC region (30.6%) and LSC region (35.31%). Phylogenetic analysis suggested that Camellia leyeensis is closely related to C. anlungensis with 96% bootstrap support. This chloroplast genome would be helpful for the phylogeny and conservation of Camellia.
10.1080/23802359.2022.2068980
pubmed_951_99
Sera from normal volunteers, patients with a variety of non-neoplastic diseases and patients with malignant or benign tumors were examined by two-dimensional acrylamide gel electrophoresis. In this technique the serum is first separated in an acrylamide gel column followed by a second electrophoresis at right angles to the first separation in a continuous concave 2 to 30 percent gradient acrylamide gel slab. The stained two-dimensional gel slab appears as a "fingerprint" pattern or "map" of the separated serum proteins. Both qualitative and quantitative differences in the fingerprint patterns of cancer-patient sera were observed. The quantitative alterations did not appear specifically associated with malignant tumors. However, several qualitative differences were detected, of which some may represent markers of malignancy as they were not observed in the normal, abnormal and benign tumors control sera. At least one of the abnormal protein stained spots, a prealbumin, appears to be restricted and related in some way to cancer of the lymphoreticular system. These data, although limited, support earlier indications that two-dimensional acrylamide gel electrophoresis offers a new and powerful tool to the cancer scientist for the detection of alterations in cancer-patient sera. A discussion of its possible use to examine other biological fluid and tumor extracts from the cancer patient is presented.
pubmed_951_99
pubmed_527_18370
Imprinted inactivation of the paternal X chromosome in marsupials is the primordial mechanism of dosage compensation for X-linked genes between females and males in Therians. In Eutherian mammals, X chromosome inactivation (XCI) evolved into a random process in cells from the embryo proper, where either the maternal or paternal X can be inactivated. However, species like mouse and bovine maintained imprinted XCI exclusively in extraembryonic tissues. The existence of imprinted XCI in humans remains controversial, with studies based on the analyses of only one or two X-linked genes in different extraembryonic tissues. Here we readdress this issue in human term placenta by performing a robust analysis of allele-specific expression of 22 X-linked genes, including XIST, using 27 SNPs in transcribed regions. We show that XCI is random in human placenta, and that this organ is arranged in relatively large patches of cells with either maternal or paternal inactive X. In addition, this analysis indicated heterogeneous maintenance of gene silencing along the inactive X, which combined with the extensive mosaicism found in placenta, can explain the lack of agreement among previous studies. Our results illustrate the differences of XCI mechanism between humans and mice, and highlight the importance of addressing the issue of imprinted XCI in other species in order to understand the evolution of dosage compensation in placental mammals.
10.1371/journal.pone.0010947
pubmed_398_13916
Aspirin and nonaspirin nonsteroidal antiinflammatory drugs (NSAIDs) inhibit platelet cyclooxygenase, thereby blocking the formation of thromboxane A2. These drugs produce a systemic bleeding tendency by impairing thromboxane-dependent platelet aggregation and consequently prolonging the bleeding time. Aspirin exerts these effects by irreversibly blocking cyclooxygenase and, therefore, its actions persist for the circulating lifetime of the platelet. Nonaspirin NSAIDs inhibit cyclooxygenase reversibly and, therefore, the duration of their action depends on specific drug dose, serum level, and half-life. The clinical risks of bleeding with aspirin or nonaspirin NSAIDs are enhanced by the concomitant use of alcohol or anticoagulants and by associated conditions, including advanced age, liver disease, and other coexisting coagulopathies.
10.1002/j.1552-4604.1995.tb04050.x
pubmed_1015_1824
The incidence of chlamydia trachomatis infection of the cervix during pregnancy was found to be 18% in a group of 1,327 women attending the prenatal clinic of a large urban hospital. There were no statistically significant differences between infected and uninfected women in the type or frequency of complications of pregnancy. Chlamydial infection was demonstrated in 27 (28%) of 95 infants born vaginally to infected mothers. Conjunctival infection in these infants was detected earlier than nasopharyngeal infection and the conjunctivae appeared to be the usual portal of entry for the organism. Infants were observed through the age of 12 weeks. Conjunctivae, but the chlamydial pneumonia syndrome occurred in only three (17%) of 18 infants with nasopharyngeal infection.
10.1001/archpedi.1981.02130300007005
pubmed_946_2897
Habituation of the human vestibulo-ocular reflex by prolonged low-frequency (0.01 and 0.005 Hz) harmonic (sinusoidal) angular acceleration was assessed by measuring the phase advance of slow-phase eye velocity at 0.01 Hz and the time constant of slow-phase eye velocity decay after impulses of angular acceleration. A single half-hour test session produced increases in low-frequency phase advance and decreases in time constant values in all 16 normal subjects. Although all subjects showed increases in low-frequency advance from the beginning to the end of the initial test session, only a few maintained the increases between test sessions. These changes are qualitatively similar to but quantitatively less than those observed with similar testing in monkeys. For clinical testing, to minimize the effect of habituation during harmonic accelerations, the testing time at low frequencies (i.e., less than 0.1 Hz) should be as short as possible.
10.1016/s0196-0709(82)80061-6
pubmed_68_4794
To analyze interdependent transport of K and Cl, we investigated Rb (K) efflux from in vitro choroid plexus (CP) in isotonic artificial CSF (aCSF) medium containing anions or agents that alter KCl transport. Lateral ventricle CP was loaded with 86Rb for release to enable calculation of the efflux rate coefficient, k. With Cl as the main anion in control aCSF, the k value for 86Rb (K) in CP of 1 week infant rats (0.177 min-1) was 19% lower than in adults (0.218 min-1) (P < 0.005). Replacing CSF Cl with NO3 or SCN, respectively, reduced k for K in infant CP by 73% and 43%; similar anion selectivity was observed in adult tissues (P < 0.05). N-Ethylmaleimide (NEM), which stimulates KCI cotransport, significantly enhanced K efflux in infants and adults. In adult CP, the KCl cotransport inhibitor, furosemide (1 mM), decreased K efflux by 23% or 65%, respectively, when aCSF had Cl or NO3 as the main anion. In infant rat CP, 0.1 mM bumetanide (another KCl cotransport inhibitor), reduced k for K by 65%, whereas the Cl channel blocker diphenylamine carboxylate (1 mM) did not significantly alter K efflux. The collective findings for rat CP indicate a substantial component of K efflux that is associated with Cl concentration and the Cl transport protein sensitive to loop diuretics and NEM. The Cl-dependent K efflux is present in infants.
10.1016/0304-3940(94)90393-x
pubmed_894_12264
Damage to the internal viscosity of red cell is correlated with changes in the surface area to volume ratio and to prelytic phenomena. Considerable changes in shape were noticed in red cells from shocked dogs and some critically ill patients in blood smear or fresh preparation, or after in vitro treatment with colloidal plasma substitutes or glucose, and so erythrocyte filterability was investigated in critically ill patients, given or not given parenteral nutrition. The results revealed an increase of the erythrocyte filtration time (EFT 1/2) in more than 50% of the critically ill patients and less alteration in critically ill patients given total parenteral nutrition, the mortality being half as great. The return of increased EFT 1/2 to normal values occurred after 3-12 days of total parenteral nutrition in 6 patients investigated. A death rate twice as great was seen in patients with high EFT 1/2 as compared to the 27.7% mortality in patients with normal EFT 1/2, its correlation with increased filtration time being significant, r = 0.81 greater than 3 Sr, y = 1.291x + 27.44, n = 47.
10.1016/0300-9572(83)90031-x
pubmed_962_2960
Nanocrystalline TiO2 thin films composed of densely packed grains were deposited onto indium-doped tin oxide (ITO)-coated glass substrates at room temperature using a chemical bath deposition technique. A layer-by-layer (LbL) process was utilized to obtain a 1.418-microm-thick TiO2/ZnO structure. The TiO2 surface was super-hydrophilic, but its hydrophilicity decreased considerably after ZnO deposition. Other TiO2/ZnO films were studied to assess their suitability as photoelectrodes in dye-sensitized solar cells (DSSCs).
10.1021/jp0531560
pubmed_1043_7675
The effect of various compounds: NAD+, NADP+, Adenosine Diphospho-Ribose, Nicotinamide, Ribose 5 Phosphate, Adenosine, cAMP, cGMP, on the growth of granulocytic and erythroid mouse bone marrow colonies (CFUc and CFUE) was evaluated. The substances were either added directly to the semi-solid culture system, to obtain a continuous exposure during colony growth, or preincubated for various times with bone marrow cells before plating. The results indicate an inhibitory effect on the number of both colonies of several adenosine containing compounds. The effect is concentration dependent and irreversible. CFUE and CFUC show different sensitivity to the inhibition.
pubmed_1043_7675
pubmed_484_860
Adult traíra (Hoplias malabaricus) were submitted to different periods of food deprivation (from 30 to 240 days) and refed for 30 days after 90 and 240 days of starvation. Stomach length remained constant during all the experimental period. However, the intestine length was significantly reduced after 30 days of food deprivation. Normal length was not recovered after refeeding. The number of pyloric caeca did not change significantly. Conversely, caeca thickness decreased after 150 days of starvation and their length decreased after 180 days. After refeeding, however, the pyloric caeca recovered original thickness. In fish refed after 240 days of starvation the length of these structures seemed to present compensatory growth, becoming longer than in the control group.
10.1590/s1519-69842004000400017
pubmed_1135_19538
We report a case of a 44-year-old man who presented with a left medial canthal mass and epiphora. Imaging was suggestive of a mass continuous with the nasolacrimal sac. Subsequent surgical exploration revealed a mass adherent to bone with invasion of the lacrimal system. Histological examination revealed a squamous/transitional cell papilloma overlying a low-grade mucoepidermoid carcinoma (MEC). Complete surgical resection was completed and pathology confirmed the diagnosis. This is the first case in which a MEC has been reported concurrently with an overlying papilloma, providing support for the hypothesis that MECs arise from papillomas in the lacrimal sac. Additionally, the tissue stained positive for p63, which is congruent with MEC immunoreactivity in the salivary gland. The description of these unique histopathological findings may assist in definitive diagnosis and improve our understanding of the pathophysiology underlying lacrimal sac MEC tumors.
10.3109/01676830.2015.1049370
pubmed_810_9070
Esophageal surgery has developed for almost 100 years. Esophagectomy can be performed via left, right thoracotomy, even via hiatus without thoracotomy due to its unique anatomic characteristics. Left thoracotomy was the initial approach in the world, and has still been performed by Chinese colleagues, but Ivor Lewis (right side thoracotomy) procedure is popular in western countries. Currently, esophagectomy by right thoracotomy has been accepted worldwide since its radical dissection for tumor. Therefore, video-assisted thoracoscopic esophagectomy based on right thoracotomy will be the mainstream surgery for esophageal cancer in the future since its minimal invasion and tumor dissection.
pubmed_810_9070
pubmed_806_5573
BACKGROUND Bronchial carcinoids are characterized by neuroendocrine differentiation and have distinct biological behavior, recurrence patterns, and prognosis compared with adenocarcinomas or squamous cell carcinomas. Because of their often indolent nature, it has been suggested that routine postoperative imaging surveillance may not be warranted in the majority of patients. This study aims to define the factors that predict disease-free survival (DFS) and recurrence after resection of these tumors, with the goal of identifying high-risk patients for whom image surveillance may be warranted. METHODS We conducted a retrospective review of a prospective database to identify patients with completely resected bronchial carcinoid tumors. Surgical procedure, histology, pathological stage, follow-up, tumor recurrence, and survival were assessed. RESULTS One hundred and forty-two patients were identified. Median age was 62 years and the majority was women (106). Surgical procedures included 20 wedge resections, 10 segmentectomies, 99 lobectomies, 3 bilobectomies, 2 pneumonectomies, 6 sleeve resections, and 2 bronchectomies. Pathologic stages included I (81%), II (10%), III (8%), and IV (1%). With a median follow-up of 31 months, there were seven recurrences. The 5- and 10-year overall survival rates were 92% and 75% and DFS rates were 88% and 72%, respectively. There were 34 patients with atypical carcinoids, and 6 (18%) developed recurrence, compared with 1 recurrence (1%) in the group of 108 patients with typical carcinoids (p = 0.0008). For atypical carcinoid tumors, the 5- and 10-year DFS rates were 72% and 32% versus 92% and 85% in typical carcinoid tumors (p = 0.001). Patients with more advanced tumor stage pT2-4 and pathologic N1/N2 nodal metastases had a significantly decreased 5- and 10-year DFS compared with those with early pT1 stage (p = 0.029) or those without nodal disease (p = 0.043). Multivariate Cox regression analyses showed advancing age (p = 0.001), atypical histology (p = 0.021), and advanced tumor stage (p = 0.047) were significant negative predictors for DFS. CONCLUSION Long-term survival after resection of bronchial carcinoids is common, especially for patients with typical carcinoid tumors. DFS can be negatively influenced by atypical histology, advanced tumor, and nodal statuses. Efforts at postoperative image surveillance should target those patients with such high-risk factors.
10.1055/s-0035-1544211
pubmed_690_3114
Success rates of up to 80% can be expected after surgical treatment of abnormal uteri. A careful investigation should be conducted to verify that other causes of prematurity are not present prior to surgical intervention.
pubmed_690_3114
pubmed_977_351
OBJECTIVE This study aimed to test the hypothesis that fibromyalgia is associated with a human enteroviral infection. METHODS Venous peripheral blood samples from 27 patients fulfilling the American College of Rheumatology revised diagnostic criteria for fibromyalgia and from 26 age- and sex-matched controls, who underwent immunofluorescence assays for coxsackievirus A7 IgG, coxsackievirus B1 IgG, coxsackievirus A7 IgA, coxsackievirus B1 IgA, echovirus IgG, and echovirus IgA. These immunological tests were performed blind to group status. RESULTS There were no significant differences between the patient and control groups in respect of positive results for coxsackievirus A7 IgG (p=0.467), coxsackievirus B1 IgG (p=0.491), coxsackievirus A7 IgA (p=0.586), coxsackievirus B1 IgA (p=0.467), echovirus IgG (p=0.236), and echovirus IgA (p=1). CONCLUSIONS The results of this systematic study do not support the hypothesis that fibromyalgia is associated with infection by a human enterovirus.
10.1590/1806-9282.20220139
pubmed_851_10027
Active surveillance (AS) has emerged as a beneficial strategy for management of low risk prostate cancer (PCa) and prevention of overtreatment of indolent disease. However, selection of patients for AS using traditional 12-core transrectal prostate biopsy is prone to sampling error and presents a challenge for accurate risk stratification. In fact, around a third of men are upgraded on repeat biopsy which disqualifies them as appropriate AS candidates. This uncertainty affects adoption of AS among patients and physicians, leading to current AS protocols involving repetitive prostate biopsies and unclear triggers for progression to definitive treatment. Prostate magnetic resonance imaging (MRI) has the potential to overcome some of these limitations through localization of significant tumors in the prostate. In conjunction with MRI-targeted prostate biopsy, improved sampling and detection of clinically significant PCa can help streamline the process of selecting suitable men for AS and early exclusion of men who require definitive treatment. MRI can also help minimize the invasive nature of monitoring for disease progression while on AS. Men with stable MRI findings have high negative predictive value for Gleason upgrade on subsequently biopsy, suggesting that men may potentially be monitored by serial MRI examinations with biopsy reserved for significant changes on imaging. Targeted biopsy on AS also allows for specific sampling of concerning lesions, although further data is necessary to evaluate the relative contribution of systematic and targeted biopsy in detecting the 25-30% of men who progress on AS. Further research is also warranted to better understand the nature of clinically significant cancers that are missed on MRI and why certain men have progression of disease that is not visible on prostate MRI. Consensus is also needed over what constitutes progression on MRI, when prostate biopsy can be safely avoided, and how to best utilize this additional information in current AS protocols. Despite these challenges, prostate MRI, either alone or in conjunction with MRI-targeted prostate biopsy, has the potential to significantly improve our current AS paradigm and rates of AS adoption among patients moving forward.
10.21037/tau.2017.05.05
pubmed_32_14870
This review deals with retinopathy of prematurity (ROP), a disease characterized by retinovitreal neovascularization, eventually retinal detachment and blindness. Due to the increasing number of extremely premature newborns, it is becoming more frequent. ROP of all stages occurs in 25-35% of surviving premature newborns of gestational age up to approximately 35 weeks. Stages 3 or more occur in 5-10%, blindness in 3-5% of very immature babies. The incidence is inversely related to gestational age. Classification is internationally unified (ICROP) and describes 5 stages. Its pathogenesis has not yet been clarified. More or less proven risk factors are retinovascular immaturity, hyperoxia and possibly circulatory and respiratory instability. Prophylaxis consists in avoiding hyperoxia, and probably also in keeping the extremely premature newborn stable. Ophthalmologic examinations must be performed by ophthalmologists experienced in this field or under their direct responsibility and must be standardized. Treatment of ROP can be carried out at a certain stage by coagulation therapy.
10.1007/BF01701481
pubmed_494_7157
According to the human platelet alloantigens (HPA) polymorphisms in five systems, the distributions of HPA-1 -3, 5, and 15 systems in 1 000 Chinese donors were carried out by using a polymerase chain reaction with sequence-specific primers (PCR-SSP) method. The genetic distance and phylogenetic tree between Chinese Hans and other populations were estimated by using DISPAN and PHYLIP software. As presented by the phylogenetic tree, Asian had a convergence with European first, and grouped together with African. Beninese which came from Africa was on the top of dendrogram. Indian was located between Asian and European. Brazilian was converged with other Europe populations. Oceanian Polynexiya had been shown specifically to cluster with Asia populations. These results proved the "out of Africa theory" from one side, and it also confirmed that early migration of Asian is from south to southeast, and east Asia., thus it is probable that Europeans are migrated from south to north, and west Europe. As genetic distance was estimated effectively by HPA systems, HPA systems could serve as the genetic marker in human migration and evolution research.
10.3724/sp.j.1005.2008.00838
pubmed_216_18326
A new thermosensitive hydrogel was designed and prepared by simply mixing N-[(2-hydroxy-3-trimethylammonium) propyl] chitosan chloride (HTCC) and poly(ethylene glycol) (PEG) with a small amount of alpha-beta-glycerophosphate (alpha-beta-GP). The optimum preparative condition was investigated, and the obtained formulation underwent thermal transition from solution below or at room temperature to non-flowing hydrogel around 37 degrees C in several minutes. As a new formulation, its potential use as nasal drug delivery system was studied. It can be dropped or sprayed easily into nasal cavity and spread on the nasal mucosa in solution state. After being administered into nasal cavity, the solution transformed into viscous hydrogel at body temperature, which decreased nasal mucociliary clearance rate and released drug slowly. Morever, quaternized chitosan as absorption enhancer has been studied extensively in several reports and proved its non-toxicity, mucoadhesivity and the capacity to open the tight junctions between epithelial cells. Therefore, in this study insulin as a model drug was entrapped in this formulation and its release behavior in vitro was also investigated. The enhancement of absorption of fluorescein isothiocyanate (FITC)-labeled insulin in rat nasal cavity by this formulation was proved by confocal laser scanning microscopy (CLSM). The cytoxicity and the change of the blood glucose concentration after nasal administration of this hydrogel were also investigated. The hydrogel formulation decreased the blood glucose concentration apparently (40-50% of initial blood glucose concentration) for at least 4-5h after administration, and no apparent cytoxicity was found after application. These results showed that HTCC-PEG-GP formulation can be used as nasal drug delivery system to improve the absorption of hydrophilic macromolecular drugs.
10.1016/j.biomaterials.2006.12.024
pubmed_489_23955
AIM OF THE STUDY This study aimed to evaluate 8-OHdG and hypoxia-inducible factor 1 (HIF-1α) levels in patients with hypoactive thyroid nodules (toxic multi-nodular goiter, Graves' disease, and Hashimoto's thyroiditis), as these parameters may be related to oxidative stress and the pathogenesis of cancer. MATERIAL AND METHODS The study included patients diagnosed with Graves' disease (n = 20), toxic multinodular goiter (n = 20), and Hashimoto thyroiditis (n = 20), and 20 healthy controls. HIF-1α levels were measured in blood samples and 8-OHdG levels were measured in urine - both via ELISA. RESULTS HIF-1α and 8-OHdG levels were significantly higher in the patient groups than in the control group (p < 0.05). In the Hashimoto's thyroiditis patients a correlation was observed between 8-OHdG and thyroglobulin antibodies (p = 0.03). A significant relation was found between 8-OHdG and HIF-1α in the patient group (p < 0.01). Carcinoma was detected in 7 of 43 female patients, but not in any of the male patients. No difference was observed in 8-OHdG or HIF-1α levels between the patients with and without papillary carcinoma (p > 0.05). There was no significant difference in 8-OHdG or HIF-1α levels between the patients with biopsy results that were benign, malignant, and non-diagnostic (p > 0.05). CONCLUSIONS Serum HIF-1α and urine 8-OHdG levels were significantly higher in the patients with thyroid diseases; however, a relationship with cancer was not observed.
10.5114/wo.2013.33774
pubmed_374_5165
Poultry can become infected with avian influenza viruses (AIV) via (in) direct contact with infected wild birds. Free-range chicken farms in the Netherlands were shown to have a higher risk for introduction of low pathogenic avian influenza (LPAI) virus than indoor chicken farms. Therefore, during outbreaks of highly pathogenic avian influenza (HPAI), free-range layers are confined indoors as a risk mitigation measure. In this study, we characterized the seasonal patterns of AIV introductions into free-range layer farms, to determine the high-risk period. Data from the LPAI serological surveillance programme for the period 2013-2016 were used to first estimate the time of virus introduction into affected farms and then assess seasonal patterns in the risk of introduction. Time of introduction was estimated by fitting a mathematical model to seroprevalence data collected longitudinally from infected farms. For the period 2015-2016, longitudinal follow-up included monthly collections of eggs for serological testing from a cohort of 261 farms. Information on the time of introduction was then used to estimate the monthly incidence and seasonality by fitting harmonic and Poisson regression models. A significant yearly seasonal risk of introduction that lasted around 4 months (November to February) was identified with the highest risk observed in January. The risk for introduction of LPAI viruses in this period was on average four times significantly higher than the period of low risk around the summer months. Although the data for HPAI infections were limited in the period 2014-2018, a similar risk period for introduction of HPAI viruses was observed. The results of this study can be used to optimize risk-based surveillance and inform decisions on timing and duration of indoor confinement when HPAI viruses are known to circulate in the wild bird population.
10.1111/tbed.13649
pubmed_15_7725
Children (aged 6-10) and adults (total N = 136) completed a novel visual perspective-taking task that allowed quantitative comparisons across age groups. All age groups found it harder to judge the other person's perspective when it differed from their own. This egocentric interference did not decrease with age, even though, overall, performance improved. In addition, it was more difficult to judge one's own perspective when it differed from that of the other person, suggesting that the other's perspective was processed even though it interfered with self-perspective judgments. In a logically equivalent, nonsocial task, the same degree of interference was not observed. These findings are discussed in relation to recent findings suggesting precocious theory-of-mind abilities in infancy.
10.1111/j.1467-8624.2011.01730.x
pubmed_524_11288
We adopt two-dimensional Langevin dynamics simulations to study the effective interactions between two passive colloids in a bath crowded with active particles. We mainly pay attention to the significant effects of active particle size, crowding-activity coupling, and chirality. First, a transition of depletion force from repulsion to attraction is revealed by varying particle size. Moreover, larger active crowders with sufficient activity can generate strong attractive force, which is in contrast to the cage effect in passive media. It is interesting that the attraction induced by large active crowders follows a linear scaling with the persistence length of active particles. Second, the effective force also experiences a transition from repulsion to attraction as volume fraction increases, as a consequence of the competition between the two contrastive factors of activity and crowding. As bath volume fraction is relatively small, activity generates a dominant repulsion force, while as the bath becomes concentrated, crowding-induced attraction becomes overwhelming. Lastly, in a chiral bath, we observe a very surprising oscillation phenomenon of active depletion force, showing an evident quasiperiodic variation with increasing chirality. Aggregation of active particles in the vicinity of the colloids is carefully examined, which serves as a reasonable picture for our observations. Our findings provide an inspiring strategy for the tunable active depletion force by crowding, activity, and chirality.
10.1103/PhysRevE.103.022604
pubmed_85_8706
BACKGROUND Surgery is required in approximately one-third of patients with chronic radiation enteritis (CRE). The aim of this study was to explore the short- and long-term outcomes after surgery for CRE and risk factors of postoperative morbidity. METHODS Clinical features and surgical outcomes of patients undergoing surgery for CRE were retrospectively reviewed. Risk factors of postoperative morbidity were analyzed using univariate and multivariate analysis. Survival and reoperation rates for CRE were evaluated. RESULTS Among the 404 patients included, 351 patients (86.88%) received resectional surgery, whereas the remaining patients received conservative procedures. No differences were detected between patients with resection and those without resection with regard to major morbidity (P = 0.486) and surgical complications (P = 0.715). Laparoscopy resulted in a shorter postoperative hospital stay (P = 0.035). After multivariate analysis, history of hypertension (odds ratio [OR] = 2.490; P = 0.046), previous acute radiation enteritis (OR = 1.832; P = 0.033), intraoperative blood loss of more than 200 mL (OR = 2.235; P = 0.006), and thrombocytopenia (OR = 2.544; P = 0.016) were determined as independent predictors of postoperative major morbidity. During follow-up, 22 patients required reoperation for CRE recurrence, and the reoperation rate was significantly lower in patients receiving resectional surgery (P = 0.005). CONCLUSIONS Resection is feasible for CRE with acceptable postoperative morbidity and lower reoperation rate. Correction of preoperative thrombocytopenia, minimizing intraoperative blood loss, and close monitoring of hypertensive patients and those with history of acute radiation enteritis are critical to reduce postoperative complications.
10.1016/j.jss.2016.05.014
pubmed_398_13595
PURPOSE Rotational therapy treatment planning for rotationally symmetric geometry of tumor and healthy tissue provides an important example of testing various approaches to optimizing dose distributions for therapeutic x-ray irradiations. In this article, dose distribution optimization is formulated as a variational problem. This problem is solved analytically and numerically. METHODS AND MATERIALS The classical Lagrange method is used to derive equations and inequalities that give necessary conditions for minimizing the mean-square deviation between the ideal dose distribution and the achievable dose distribution. The solution of the resulting integral equation with Cauchy kernel is used to derive analytical formulas for the minimizing irradiation intensity function. RESULTS The solutions are evaluated numerically and the graphs of the minimizing intensity functions and the corresponding dose distributions are presented. CONCLUSIONS The optimal solutions obtained using the mean-square criterion lead to significant underdosage in some areas of the tumor volume. Possible solutions to this shortcoming are investigated and medically more appropriate criteria for optimization are proposed for future investigations.
10.1016/0360-3016(95)00569-k
pubmed_942_14754
The West of Scotland Coronary Prevention Study (WOSCOPS), a placebo-controlled 5-year cohort study, demonstrated that the use of pravastatin decreased low density lipoprotein (LDL) levels and associated risk of myocardial infarction. The rate of occurrence of coronary events, however, was similar across the four lowest quintiles of LDL reduction (23-41% reductions in mean LDL levels). The relationship between reduction of LDL and the reduction of risk was not linear. Further analysis indicated that even in overlap groups where patients exhibited equivalent mean LDL levels on treatment, pravastatin treatment was associated with less risk of occurrence of coronary events than placebo treatment. These results suggest that while LDL level does serve as a predictor of the risk of coronary events, other factors exist that should be considered and investigated further.
10.1046/j.1524-4733.1998.120120.x
pubmed_1138_9018
Tertiary amines like imidazole and triallylamine lower the apparent affinity of K+ in the ATP hydrolysis reaction of pig gastric H,K-ATPase in a pH and amine concentration dependent way. The mechanism and sidedness of this effect was studied by analyzing the partial reactions of the enzyme in both leaky and ion-tight vesicles. In leaky vesicles Tris and Hepes had nearly no effect on the apparent Km for K+ in the ATPase reaction, but imidazole (Ki = 13 mM) and triallylamine (Ki = 1.6 mM) markedly decreased the K+ affinity. The steady-state ATP-phosphorylation level in the absence of K+ was not or only slightly affected by these compounds. The reduction of the ATP-phosphorylation level by K+, however, again depended on both the type and concentration of tertiary amine used. A comparable K(+)-amine antagonism was observed in the dephosphorylation reaction. In tightly sealed vesicles, where no activation of K+ at the luminal side could occur, K+ reduced the affinity for ATP in the phosphorylation reaction. Triallylamine counteracted this effect. The K(+)-activated p-nitrophenylphosphatase activity in these ion-tight vesicles also showed a K(+)-triallylamine antagonism. Inhibition of H,K-ATPase activity in these vesicles by triallylamine was immediate (with nigericin present in order to allow intravesicular K+ activation), suggesting the transmembrane feature of this inhibition. These results indicate that tertiary amines decrease the affinity for K+ at both luminal and cytosolic binding sites by interaction at the cytosolic side of the membrane. This results in shifts in the equilibrium of both the E1.H<==>E1.K transition and in the dephosphorylation reaction, E2-P-->E2.K.
10.1016/0005-2736(94)90059-0
pubmed_1069_9178
Control of intracellular Ca2+ ([Ca2+]i) is critical to vascular smooth muscle function. Calcium channels are the major route by which Ca2+ enters the smooth muscle cell. This article reviews the types of calcium channel present in vascular smooth muscle cells and their physiological and biochemical regulation.
10.1159/000159111
pubmed_765_12318
The 2019 novel coronavirus (SARS-CoV-2) outbreak is a major challenge for public health. SARS-CoV-2 infection in human has a broad clinical spectrum ranging from mild to severe cases, with a mortality rate of ~6.4% worldwide (based on World Health Organization daily situation report). However, the dynamics of viral infection, replication and shedding are poorly understood. Here, we show that Rhesus macaques are susceptible to the infection by SARS-CoV-2. After intratracheal inoculation, the first peak of viral RNA was observed in oropharyngeal swabs one day post infection (1 d.p.i.), mainly from the input of the inoculation, while the second peak occurred at 5 d.p.i., which reflected on-site replication in the respiratory tract. Histopathological observation shows that SARS-CoV-2 infection can cause interstitial pneumonia in animals, characterized by hyperemia and edema, and infiltration of monocytes and lymphocytes in alveoli. We also identified SARS-CoV-2 RNA in respiratory tract tissues, including trachea, bronchus and lung; and viruses were also re-isolated from oropharyngeal swabs, bronchus and lung, respectively. Furthermore, we demonstrated that neutralizing antibodies generated from the primary infection could protect the Rhesus macaques from a second-round challenge by SARS-CoV-2. The non-human primate model that we established here provides a valuable platform to study SARS-CoV-2 pathogenesis and to evaluate candidate vaccines and therapeutics.
10.1038/s41422-020-0364-z
pubmed_883_7320
The following work presents the case of undesired during side effect (toxic hepatocellular damage ) by Simvastatine (Cardin). The main syptoms were jaundice and pruritus. Conclusions draw the attention to the role of history taking in the diagnosis of the described disease, as well as the importance of regular patient checkups whoin those use statines.
pubmed_883_7320
pubmed_598_9666
The resistance due to the convergence from bulk to a constriction, for example, a nanopore, is a mainstay of transport phenomena. In classical electrical conduction, Maxwell, and later Hall for ionic conduction, predicted this access or convergence resistance to be independent of the bulk dimensions and inversely dependent on the pore radius, a, for a perfectly circular pore. More generally, though, this resistance is contextual, it depends on the presence of functional groups/charges and fluctuations, as well as the (effective) constriction geometry/dimensions. Addressing the context generically requires all-atom simulations, but this demands enormous resources due to the algebraically decaying nature of convergence. We develop a finite-size scaling analysis, reminiscent of the treatment of critical phenomena, that makes the convergence resistance accessible in such simulations. This analysis suggests that there is a "golden aspect ratio" for the simulation cell that yields the infinite system result with a finite system. We employ this approach to resolve the experimental and theoretical discrepancies in the radius-dependence of graphene nanopore resistance.
10.1039/c7cp07924a
pubmed_740_21049
The objective of this study was to review the medical records of patients with a history of mandibular angle fracture who were attended at the Service of Oral and Maxillofacial Surgery and Traumatology of FOAr/UNESP in the last 5 years. The data collected were subjected to chi-squared test (significance level of 5%). The authors reviewed 19 medical records. The main cause was physical aggression (58.00%), but with no statistical difference in relation to the other etiologies (P > 0.05). Regarding the type of fixation, one 2.0-mm system plate associated with one 2.4-mm system plate and the fixation using only two 2.0-mm system plates were used in 7 patients each. The fixation method with a monocortical plate at the upper border was used in 5 patients. However, there was no statistically significant difference in the frequency of complications among the 3 fixation methods used (P > 0.05). In 52.64% of the patients, the third molar was removed intraoperatively. Despite this, there was no statistically significant difference in the frequency of complications when the third molar was in the fracture line or when it was removed postoperatively (P > 0.05). The complications observed were dehiscence associated with pain (44.44%), trismus (22.22%), infection (22.22%), and presence of bone spicules (11.11%). However, no statistical differences were observed between the frequency of different types of complications (P = 0.779). In the sample studied, there were no differences in the frequency of complications among the fixation methods applied.
10.1097/SCS.0000000000004484
pubmed_361_4222
We have used human CD4+ T lymphocyte clones as primary probes to identify and isolate lambda gt11 rDNA clones that express epitopes recognized by T cells. The method that we describe here permits a direct survey of T cell epitope coding sequences in genomic DNA or cDNA libraries. A lambda gt11 library of Mycobacterium leprae DNA was screened with M. leprae-reactive human T cell clones as probes, allowing the isolation of a M. leprae DNA clone encoding the unidentified Ag. This DNA clone differs in restriction maps from those previously identified by antibody probes and encodes an epitope that is unique to vaccine strains of Mycobacterium bovis bacillus Calmette-Guérin and pathogenic mycobacteria. This method is generally applicable and should expedite the study of Ag and epitopes important to the T cell response in infections and in autoimmune diseases.
pubmed_361_4222
pubmed_41_15718
In more than a decade, the adoption and use of some type of social media among American adults has risen from 5% in 2005 to nearly 70% in 2016. The reigning social media platform by usage, Facebook, has 142% more American adult users than the second most utilized social media platform, Instagram, which was purchased by Facebook in March 2012. Of the 68% of American adult Facebook users, more than three quarters visit the site daily. Although social media applications (apps) such as Facebook and Instagram are the clear draw among users, health care apps are beginning to gain traction as well. In 2017, 32% of consumers now have at least 1 health app on their smartphones or tablets, doubling over the past 4 years. Although having an app should not be confused with using an app, having an app downloaded and available for use is a step closer to ongoing adoption. Mobile apps in health care are being used for ordering and scheduling health care services, as well as tracking and managing aspects of health and wellness. An incredible opportunity now exists to connect and leverage social media to enhance the impact of health care, particularly in the areas of drug development, clinical trial recruitment, and therapy administration and adherence, in which dose reminders, sharing of side effects and response, and the accessibility of patients to one another has both a context and a platform. This commentary serves as an introduction to the ways that social media and mobile health care apps are being used in real-world settings as tools to advance the development and effectiveness of clinical therapeutics.
10.1016/j.clinthera.2017.10.007
pubmed_365_19260
A report is presented on four HIV-positive homosexual men examined after several months of exposure during cleaning of a flat from masses of pigeon droppings heavily colonized by Cryptococcus neoformans. Only one out of the four persons, with a CD4 lymphocyte count of 50/microL, fell sick from systemic cryptococcosis, but not the others, with CD4 lymphocyte counts of 180, 250, and 630/microL, respectively; they remained clinically and mycologically inconspicuous and free from C. neoformans. Open questions in view of the epidemiology of opportunistic pathogens in AIDS are discussed with regard to the CD4 cell count as a parameter indicating a predisposition for cryptococcosis as an airborne AIDS-defining opportunistic infection. This has been confirmed by specific cultural diagnosis of the agent in both the environment and the patient. Already in 1987/88, the probable source of infection had been the subject of epidemiological studies on C. neoformans in Berlin.
10.1016/s0934-8840(11)80899-6