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pubmed_565_19348
OBJECTIVE To compare the acute effects of the beta-blocker propranolol (CAS 525-66-6), beta + alpha1-blocker carvedilol (CAS 72956-09-3) and alpha1-blocker tamsulosin (CAS 106463-17-6) on the cardiovascular responses to passive orthostasis. METHODS The responses to passive orthostasis (tilt provocation at 60 degress for 8 min) were measured in normotensive healthy volunteers with finger-blood-pressure and whole-body impedance cardiography prior to drugs and three days after beginning the medications. The treatments were moderate oral doses of the beta-blocker propranolol HCl (40 mg twice daily, n = 7), (beta + alpha1-blocker carvedilol (12.5 mg once daily for two days and thereafter 25 mg daily, n = 7), alpha1-blocker tamsulosin HCl (0.4 mg once daily, n = 6), or placebo. The drugs were distributed in a randomised, double-blind fashion. RESULTS When measured prior to the head-up tilt test, propranolol and carvedilol had decreased supine systolic arterial pressure (SAP) more than placebo, and heart rate (HR) more than placebo and tamsulosin. Propranolol had decreased also pulse wave velocity more than placebo. The cardiac index (CI), stroke index (SI) and systemic vascular resistance index (SVRI) were not changed with any drugs. During the head-up tilt, tamsulosin decreased SAP and SVRI and augmented CI but not SI. The SVRI response curve with tamsulosin differed from that with propranolol or carvedilol. Also, tamsulosin increased HR compared to the beta-blocking drugs. The propranolol and carvedilol groups did not differ from each other in terms of any parameter. CONCLUSIONS Tamsulosin significantly decreases SAP in the passive head-up tilt, indicating that it is not purely uroselective alpha1-blocker. The responses with tamsulosin clearly differ from those with propranolol and carvedilol, the responses with the latter two being practically equal.
10.1055/s-0031-1296846
pubmed_727_4186
The deposition and clearance of various fibrous materials have been investigated in the rat using radioactive tracer techniques. The materials used include the U.I.C.C. standard reference samples and synthetic mineral fibres. Measurements of total and alveolar deposition were correlated with the AMADs of the radioactive dust samples which ranged from 1 to 2.5 micron. Although total deposition increases steeply over this range, alveolar deposition is relatively constant only increasing from about 10 to 13%. Alveolar deposition is lower than in man, but the maximum in alveolar deposition appears to occur at a similar aerodynamic diameter. Half times of alveolar clearance, measured over a period of several months following single inhalation exposures, were in the range 60-90 days and no significant difference was observed between amphibole and chrysotile asbestos. Autoradiographs of lung sections indicate that alveolar deposition is relatively uniform and occurs right up to the periphery of the lung. Over a period of several months the uniform distribution alters to one in which fibres accumulate in foci which are mainly subpleural. These foci act as centres for the development of nodular fibrosis.
pubmed_727_4186
pubmed_487_19248
BACKGROUND A high incidence of Achilles tendinopathy--tendinitis or rupture--has been observed after quinolone treatment in lung and kidney transplant patients. In the absence of relevant published data, we aimed to determine its incidence, clinical features, risk factors and outcome among heart graft recipients. METHODS We studied the clinical records of all adult heart transplant patients who were prescribed quinolones at our center between August 1995 and September 2006. Achilles tendinopathy had been diagnosed clinically, with ultrasound assessment when necessary. In all cases, quinolone treatment had been terminated upon diagnosis of tendinopathy. RESULTS During this period, quinolones had been given on 242 occasions to 149 heart transplant patients (33 women, 116 men). Achilles tendinopathy developed on 14 occasions (5.8%; 95% confidence interval: 2.8% to 8.7%), affecting 13 men and 1 woman (mean age: 62 years). Three cases involved tendon rupture, and bilateral tendinopathy was present in 8 cases. The median time between the start of treatment and onset of symptoms was 2.5 days, with 12 patients being asymptomatic 2 months after drug withdrawal. Independent risk factors for tendinopathy were renal dysfunction (p = 0.03) and increased time between transplantation and treatment (p = 0.005). Incidence was not influenced by the type, dose or previous administration of quinolones, or by the immunosuppressive regimen. CONCLUSIONS Quinolone-related Achilles tendinopathy is frequent among heart transplant patients, especially in the presence of renal dysfunction or lengthy post-transplantation survival. If no alternative anti-bacterial therapy is available for high-risk patients, close clinical surveillance should be warranted.
10.1016/j.healun.2007.09.021
pubmed_984_4920
OBJECTIVE Bertolotti's syndrome is a spine disorder characterized by the occurrence of a congenital lumbar transverse mega-apophysis in a transitional vertebral body that usually articulates with the sacrum or the iliac bone. It has been considered a possible cause of low back pain. METHOD We analyzed the cases of Bertolotti's syndrome that failed clinical treatment and reviewed the literature concerning this subject. RESULTS Five patients in our series had severe low back pain due to the neo-articulation and two of them were successfully submitted to surgical resection of the transverse mega-apophysis. Taking into account the clinical and surgical experience acquired with these cases, we propose a diagnostic-therapeutic algorithm. CONCLUSION There is still no consensus about the most appropriate therapy for Bertolotti's syndrome. In patients in whom the mega-apophysis itself may be the source of back pain, surgical resection may be a safe and effective procedure.
pubmed_984_4920
pubmed_911_73
Echinacea purpurea (L.) Moench was mistakenly taken from North America to Germany in 1939 where it was cultivated and various extractions were prepared and subsequently used to treat upper respiratory tract infections. Parents often administer Echinacea to their children, but safety data on the use of Echinacea in Canadian children is lacking. A screening history, physical examination, and daily record of symptoms from an initial visit through to a the follow-up visit 13 days later were used to increase patient safety. Each subject was administered an aerial part Echinacea extract. The dose was based on age (2.5 mL three times per day for children aged 2-5 years, and 5 mL two times per day for children aged 6-12 years) and administered for 10 days in an open-label trial. A rating scale was used to measure tolerance to the treatment. We assessed the safety and compliance of use of the Echinacea extract by measuring the amount of extract returned at the end of the study, having the parents complete and return a daily symptom diary, and recording the subjects' use of other natural health products or medications during the trial. Clinical effectiveness of the Echinacea extract could not be accurately assessed because of the small trial size and because the extract had been administered when some of the subjects had an upper respiratory tract infection that had begun 1 or more days prior to the study; however, each subject's symptoms improved. No allergic or adverse reaction occurred and no safety issues arose.
10.1139/Y07-103
pubmed_152_21714
Although care is pointed as the essence of the nursing profession, there is a lack of discussion on its meaning in the nursing education. The objective of this study is to identify the meaning of care for graduate students aiming at contributing to a more contextualized teaching. In order to guide the study, we used the concepts of affiliation and membership notion from ethnomethodology. The subjects were students from a state nursing graduation course in Rio de Janeiro. The data were collected through semi-structured interviews taken after group dynamics which objective was to apprehend the way students described care until that moment in their nursing course. We concluded that as students become more involved with nursing they incorporate concepts that contribute to reinforce or to transform their previous experiences and experiences acquired during the graduation course. Therefore, concepts and behaviors are apprehended and reproduced by students as components of their professional identity.
pubmed_152_21714
pubmed_564_21253
It has been demonstrated that protamine sulfate (PS; a cationic polypeptide composed of 70% arginine) increases the apical membrane conductance of the mammalian urinary bladder. In this report, synthetic cationic polypeptides (CpP; e.g., polyarginine) were used to determine whether the response of the bladder to PS was due to its cationic nature (i.e., its arginine content). We demonstrate that CpP induce a large increase in the cation and anion conductance of the apical membrane of the rabbit urinary bladder epithelium. The modulation of the membrane conductance by CpP is dependent upon a number of parameters. 1) The magnitude of the conductance change was voltage dependent. 2) An increase in the total charge per molecule increased the rate of conductance change. 3) An increase in the charge density (ratio of charged amino acids to total amino acids) increased the rate of change of conductance. 4) La3+ inhibited the ability of CpP to alter the membrane conductance. 5) The rate of reversal of the CpP-induced conductance was dependent upon the total charge per molecule as well as the charge density. 6) The level of self-inhibition (ability of solution CpP to inhibit the CpP-induced membrane conductance) was inversely correlated with the charge density and was also concentration dependent, with less inhibition occurring at low mucosal CpP concentrations. These data are consistent with a model developed to describe the effect of PS on the conductive properties of the urinary bladder epithelium.
10.1152/ajpcell.1993.265.6.C1637
pubmed_1030_22994
Raw feed materials are often contaminated with mycotoxins, and co-occurrence of mycotoxins occurs frequently. A total of 250 samples i.e., rice bran and maize from Cambodia, Laos, Myanmar, and Thailand were analysed using state-of-the-art liquid chromatography-mass spectrometry (LC-MS/MS) for monitoring the occurrence of regulated, emerging, and masked mycotoxins. Seven regulated mycotoxins - aflatoxins, ochratoxin A, fumonisin B1, deoxynivalenol, zearalenone, HT-2, and T-2 toxin were detected as well as some emerging mycotoxins, such as beauvericin, enniatin type B, stachybotrylactam, sterigmatocystin, and masked mycotoxins, specifically zearalenone-14-glucoside, and zearalenone-16-glucoside. Aspergillus and Fusarium mycotoxins were the most prevalent compounds identified, especially aflatoxins and fumonisin B1 in 100% and 95% of samples, respectively. Of the emerging toxins, beauvericin and enniatin type B showed high occurrences, with more than 90% of rice bran and maize contaminated, whereas zearalenone-14-glucoside and zearalenone-16-glucoside were found in rice bran in the range of 56-60%. Regulated mycotoxins (DON and ZEN) were the most frequent mycotoxin combination with emerging mycotoxins (BEA and ENN type B) in rice bran and maize. This study indicates that mycotoxin occurrence and co-occurrence are common in raw feed materials, and it is critical to monitor mycotoxin levels in ASEAN's feedstuffs so that mitigation strategies can be developed and implemented.
10.3390/toxins14080567
pubmed_466_15877
We examined the high affinity binding, uptake, and degradation of apo E-free 125I-high density lipoprotein (HDL) in cultured pig hepatocytes. At steady state, the cells degraded 9.4% of cell-associated 125I-HDL/hour, compared with 41.7%/hour for 125I-LDL. Pulse-chase experiments at 4 degrees C revealed that high affinity 125I-HDL binding was reversible. Similar experiments at 37 degrees C revealed that about 70% of the cell-associated 125I-HDL was released as a macromolecule; the remainder was degraded to acid-soluble products. In contrast, over 75% of the 125I-LDL that was released had been degraded to acid soluble products. The amount of macromolecular 125I-HDL released at 37 degrees C was similar to the amount that was bound to the cell surface, as estimated from measurements of trypsin-releasable radioactivity. Density gradient ultracentrifugation and SDS-polyacrylamide gel electrophoretic analysis of macromolecular 125I-HDL released to the medium revealed an increase in density, and the apparent partial proteolysis of apo A-I (Mr 25,000) to products of apparent Mr 12,000-14,000. The findings suggest that high affinity 125I-HDL uptake had a reversible component in which HDL was concentrated temporarily at the cell surface, modified, and then released as a somewhat denser lipoprotein particle. Measurement of 125I-HDL and 125I-LDL degradation in cell homogenates revealed no difference in the inherent susceptibility of the two lipoproteins to proteolysis by lysosomal enzymes. The overall slower rate of degradation of 125I-HDL compared to 125I-LDL was therefore due in part to the smaller fraction of HDL that was committed to irreversible catabolism. The rate of catabolism of this fraction, however, was considerable. Cells pulsed at 4 degrees C and subsequently warmed to 37 degrees C released one-half the acid-soluble products from 125I-HDL within about 4 hours, compared with 2 hours for cells pulsed with 125I-LDL. These findings indicate that HDL was internalized, transported to lysosomes, and degraded at about one-half the rate of LDL.
10.1161/01.atv.5.2.142
pubmed_1022_23978
DNA has the capacity to adopt several distinct structural forms, such as duplex and quadruplex helices, which have been implicated in cellular processes and shown to exhibit important functional properties. Quadruplex-duplex hybrids, generated from the juxtaposition of these two structural elements, could find applications in therapeutics and nanotechnology. Here we used NMR and CD spectroscopy to investigate the thermal stability of two classes of quadruplex-duplex hybrids comprising fundamentally distinct modes of duplex and quadruplex connectivity: Construct I involves the coaxial orientation of the duplex and quadruplex helices with continual base stacking across the two components; Construct II involves the orthogonal orientation of the duplex and quadruplex helices with no base stacking between the two components. We have found that for both constructs, the stability of the quadruplex generally increases with the length of the stem-loop incorporated, with respect to quadruplexes comprising nonstructured loops of the same length, which showed a continuous drop in stability with increasing loop length. The stability of these complexes, particularly Construct I, can be substantially influenced by the base-pair steps proximal to the quadruplex-duplex junction. Bulges at the junction are largely detrimental to the adoption of the desired G-quadruplex topology for Construct I but not for Construct II. These findings should facilitate future design and prediction of quadruplex-duplex hybrids.
10.1021/bi401161a
pubmed_700_12307
Cilia in the male genital tract are found on the epithelium of the ductuli efferentes, epididymis and vas deferens. Detached ciliary tufts (DCTs) were observed in semen of 13 men and this paper deals with the clinical features of these patients. There was a high incidence of smoking (73%), diminished testicular volume in 64%, a high number with previous urological surgery and trauma and an increased percentage of cytoplasmic droplets. It is postulated that DCTs originate from the epididymal ephithelium. DCTs are possibly shedded as part of epididymal involvement which occurs as a result of testicular pathology caused by several agents.
pubmed_700_12307
pubmed_849_10131
Oyster (Crassostrea talienwhanensis Crosse) proteins were produced from fresh oyster and subsequently digested with pepsin. The separations were performed with a Sephadex LH-20 gel filtration chromatography and a RP-HPLC. A purified peptide with sequence Val-Val-Tyr-Pro-Trp-Thr-Gln-Arg-Phe (VVYPWTQRF) was firstly isolated and characterized from oyster protein hydrolysate and its ACE inhibitory activity was determined with IC50 value of 66μmol/L in vitro. Stability study for ACE inhibitory activity showed that the isolated nonapeptide had the good heat and pH stability and strong enzyme-resistant properties against gastrointestinal proteases. Kinetic experiments demonstrated that inhibitory kinetic mechanism of this peptide was non-competitive and its Km and Ki values were calculated. The yield of this peptide from oyster proteins was 8.5%. Furthermore, the oyster protein hydrolysate (fraction II), prepared by pepsin treatment firstly exhibited antihypertensive activity when it was orally administered to spontaneously hypertensive rat (SHR) at a dose of 20mg/kg. These results demonstrated that the hydrolysate from oyster proteins prepared by pepsin treatment could serve as a source of peptides with antihypertensive activity.
pubmed_849_10131
pubmed_830_4752
OBJECTIVES Successful aortic valve repair must normalize cusp and root dimensions. Limited information is available on the normal dimensions of human cusps, in particular the cusp height. METHODS The cusp height was measured intraoperatively in 621 patients during aortic valve repair procedures. A tricuspid anatomy was present in 329 patients and bicuspid in 286 patients. In addition, patient age, gender, height, weight, preoperative degree of aortic regurgitation, and aortic dimensions were recorded. The data were analyzed for possible interrelation between the cusp height and clinical variables. RESULTS In the bicuspid valves, the geometric height of the nonfused cusp ranged from 15 to 30 mm (mean, 23.8 ± 2.0). Significant correlations were found between the cusp height and all clinical variables. In the tricuspid valves, the height of the noncoronary cusp ranged from 14 to 28 mm (mean, 20.7 ± 2.2). The height of the left coronary cusp varied from 12 to 25 mm (mean, 20.0 ± 2.1) and that of the right coronary cusp from 12 to 25 mm (mean, 20.0 ± 2.1). The noncoronary cusp was significantly greater than the left and the right coronary cusp (P = .000). No difference was found between the left and right cusps (P = .513). Significant correlations between the geometric height and clinical parameters were found for most clinical variables, excluding the degree of aortic regurgitation. CONCLUSIONS We found the cusp height was larger than previously published. It shows marked variability and correlates with the clinical variables. These data might serve as the basis for decision making in aortic valve repair.
pubmed_830_4752
pubmed_534_12938
OBJECTIVE To investigate the effects of nano-lead exposure on learning and memory and iron homeostasis in the brain of the offspring rats on postnatal day 21 (PND21) and postnatal day 42 (PND42). METHODS Twenty adult pregnant female Sprague-Dawley rats were randomly divided into control group and nano-lead group. Rats in the nano-lead group were orally administrated 10 mg/kg nano-lead, while rats in the control group were administrated an equal volume of normal saline until PND21. On PND21, the offspring rats were weaned and given the same treatment as the pregnant rats until 42 days after birth. The learning and memory ability of offspring rats on PND21 and PND42 was evaluated by Morris water maze test. The hippocampus and cortex s amples of offspring rats on PND21 and PND42 were collected to determine iron and lead levels in the hippocampus and cortex by inductively coupled plasma-mass spectrometry. The distributions of iron in the hippocampus and cortex were observed by Perl's iron staining. The expression levels of ferritin, ferroportin 1 (FPN1), hephaestin (HP), and ceruloplasmin (CP) were measured by enzyme-linked immunosorbent assay. RESULTS After nano-lead exposure, the iron content in the cortex of offspring rats on PND21 and PND42 in the nano-lead group was significantly higher than those in the control group (32.63 ± 6.03 µg/g vs 27.04 ± 5.82 µg/g, P<0.05; 46.20 ±10.60 µg/g vs 36.61 ± 10.2µg/g, P<0.05). The iron content in the hippocampus of offspring rats on PND42 in the nano-lead group was significantly higher than that in the control group (56.9 ± 4.37µg/g vs 37.71 ± 6.92µg/g, P<0.05). The Perl's staining showed massive iron deposition in the cortex and hippocampus in the nano-lead group. FPNl level in the cotfex of offspring rats on PND21 in the nano-lead group was significantly lower than that in the control group (3.64 ± 0.23 ng/g vs 4.99 ± 0.95 ng/g, P<0.05). FPN1 level in the hippocampus of offspring rats on PND42 in the nano-lead group was significantly lower than that in the control group (2.28 ± 0.51 ng/g vs 3.69 ± 0.69 ng/g, P<0.05). The escape latencies of offspring rats on PND21 and PND42 in the nano-lead group were longer than those in the control group (15.54 ± 2.89 s vs 9.01 ± 4.66 s; 6.16 ± 1.42 s vs 4.26 ± 1.51 s). The numbers of platform crossings of offspring rats on PND21 and PND42 in the nano- lead group were significantly lower than those in the control group (7.77 ± 2.16 times vs 11.2 ± 1.61 times, P<0.05; 8.12 ± 1.51 times vs 13.0 ± 2.21 times, P<0.05). ONCLUSION n Nano-lead exposure can result in iron homeostasis disorders in the hippocampus and cortex of offspring rats and affect their learning and memory ability.
pubmed_534_12938
pubmed_876_17199
Controlling water activity (a(w)) can significantly impact the growth of Salmonella in poultry litter and manure - a phenomenon that was studied quantitatively using two common serotypes of Salmonella. The quantitative effect of changes in levels of a(w) on Salmonella populations was determined using inoculated, frosted glass rectangles placed in closed chambers (microcosms). Glass rectangles with known concentrations of Salmonella enteritidis and S. brandenburg were placed in microcosms maintained at an a(w) level of 0.893 for 24 h at room temperature (RT) and then transferred to other microcosms maintained at the same temperature but with higher a(w) levels (0.932 and 0.987). Salmonella populations on the slides were quantified at 4, 18, 24, and 48 h. Slightly elevated levels of a(w) (<0.1, i.e., 10% equilibrium relative humidity) for 24 h resulted in a 100-fold increase in counts of Salmonella. The data also suggested that in vitro adaptation to dry environments may occur when the organisms are exposed to alternating levels of relatively high and low (0.987 and 0.893) levels of a(w). Any increased tolerance of Salmonella to reduced levels of a(w) could be the result of physico-chemical changes in the organism due to selective environmental pressure, formation of a protective biofilm, and/or entry into a dormant state. Results from this study are compatible with those from previously reported on-farm surveys, reinforcing the contention that maintaining a(w) below 0.85 in and around litter/manure surfaces in poultry or livestock bedding areas may be a critical factor in safe production of food.
10.1038/sj.jim.7000116
pubmed_133_2806
A method is proposed for the determination of dissociation constants of amino acids by capillary zone electrophoresis. According to the dissociation equilibrium of amino acids and the basic theory of electrophoresis, the nonlinear relationship between the pH value of the buffer and the effective electrophoretic mobilities of the analyte was obtained. The dissociation constants can be calculated from the pH values and the corresponding effective electrophoretic mobilities using the program written in C++. The dissociation constants, pKa1 and pKa2, of 11 kinds of amino acids were determined successfully by the proposed method. The determined dissociation constants were compared with values in the literature; the differences between them are in the range of -0.03 to 0.06. No significant differences were observed between the determined dissociation constants and the corresponding literature values.
10.1002/(SICI)1522-2683(19991001)20:14<2877::AID-ELPS2877>3.0.CO;2-Q
pubmed_64_14179
The destabilization of zein gel particles by salt ions seriously limits their practical application. In this study, zein gel particles exhibiting excellent stability to salt ions were developed by grafting gum arabic with tannic acid. Gum arabic (GA) was first coated onto the surface of zein gel particles, followed by addition of tannic acid to further reinforce non-covalent cross-linking between GA and the zein gel particle surface. The stability of the gel particle dispersions was characterized by Turbiscan analysis, gel particle diameter changes and visual inspection of phase separation. The tannic acid-treated zein-GA gel particles were highly protected from precipitation or aggregation in the presence of NaCl (0-3 mol/L) at different pH values (4.0, 7.0 or 8.5). The gel particles prepared in this study will therefore have broader applicability in different pH and salt ions ion environments.
10.3390/molecules26051458
pubmed_37_131
While male-to-male sexual behavior has been recognized as a primary risk factor for human immunodeficiency virus (HIV), research targeting men who have sex with men (MSM) in less-developed countries has been limited due to high levels of stigma and discrimination. In response, the Population Council's Horizons Program began implementing research activities in Africa and South America beginning in 2001, with the objectives of gathering information on MSM sexual risk behaviors, evaluating HIV-prevention programs, and informing HIV policy makers. The results of this nearly decade-long program are presented in this article as a summary of the Horizons MSM studies in Africa (Senegal and Kenya) and Latin America (Brazil and Paraguay), and include research methodologies, study findings, and interventions evaluated. We also discuss future directions and approaches for HIV research among MSM in developing countries.
10.1177/003335491012500222
pubmed_122_23017
Aflatoxin B1 (AFB1) is the major mycotoxin that contaminates aquafeeds and regarded as a causative agent in illnesses and the mortality of aquacultural species. However, the effects of AFB1 on developing fish and associated toxic mechanism are still unknown. This study examines the behavioral changes, neuronal morphology and gene expression in zebrafish embryos and larvae upon exposure to aflatoxin solutions. Treatment of 6 h post fertilization (hpf) embryos with AFB1 at 15-75 ng/mL significantly changed the swimming patterns of seven days post-fertilization (dpf) zebrafish larvae. Larvae in the 15 ng/mL group demonstrated a hypolocomotor activity in free swimming, but hyperlocomotion was observed in the larvae exposed to 30-75 ng/mL AFB1. AFB1 at 75 ng/mL also significantly reduced the startle response of 7 dpf larvae after tapping stimulus. Exposure to AFB1 resulted in an aberrant morphology of trigeminal ganglion and hindbrain neurons in transgenic embryos (HuC:eGFP); this finding was supported by acetylated alpha-tubulin staining in wild-type fish. Additionally, AFB1 altered the levels of neurotoxic markers, including gfap and huC. The transcriptomic profile of AFB1-treated embryos revealed several differentially expressed genes that are related to neuroactivity and neurogenesis. PCR analysis verified that AFB1 significantly down-regulated the expression of ngfa and atp1b1b genes and increased that of prtga gene. The results herein indicate the toxicological impacts of AFB1 on the behaviors and neurodevelopment of fish in the early embryonic stage. Disruption of neural formation and synapse dysfunction may be responsible for the behavioral alteration.
10.1016/j.chemosphere.2018.11.058
pubmed_154_11725
Near-field coupling between an excited atom and a surface-polariton mode can dramatically modify atomic branching ratios, because of surface-induced enhancement of a resonant decay channel. We show here that Cs(6D(3/2)) transfer towards Cs(7P(1/2)) (at lambda = 12.15 microm), negligible in free space, becomes efficient in the vicinity (< or =100 nm) of a sapphire window, due to a 12 microm resonance in the surface-polariton modes. The experiment relies on a selective reflection probing on the 7P(1/2)-10D(3/2) transition.
10.1103/PhysRevLett.88.243603
pubmed_752_5319
The electronic quenching reaction N((2)D) + N2 → N((4)S) + N2 is studied using the trajectory surface hopping method and employing two doublet and one quartet accurate potential energy surfaces. State-specific properties are analyzed, such as the dependence of the cross section on the initial quantum state of the reactants, vibrational energy transfer, and rovibrational distribution of the product N2 molecule in thermalized conditions. It is found that rotational energy on the reactant N2 molecule is effective in promoting the reaction, whereas vibrational excitation tends to reduce the reaction probability. For initial states and collision energy thermalized in an initial bath, it is found that the products are "hotter", both vibration and rotation wise.
10.1021/ct500085q
pubmed_57_18013
Lunasin is a peptide whose anticancer properties are widely reported. Originally isolated from soybean seeds, lunasin was also found in cereal (wheat, rye, barley and Triticale), Solanum and amaranthus seeds. However, it was recently reported that searches of transcript and DNA sequence databases for wheat and other cereals failed to identify sequences with similarity to those encoding the lunasin peptide in soy. In order to clarify the presence or absence of lunasin in wheat varieties, a broad investigation based on chemical (LC-ESI-MS) and molecular (PCR) analyses was conducted. Both approaches pointed out the absence of lunasin in the investigated wheat genotypes; in particular no compounds with a molecular weight similar to that of lunasin standard and no lunasin-related sequences were found in the analysed wheat samples. These findings confirm the hypothesis, reported in recent researches, that lunasin is not a wheat-derived peptide.
pubmed_57_18013
pubmed_641_17500
The age-associated decline in T lymphocyte function can be attributed in part to shifts between subsets (in particular the accumulation of memory T cells at the expense of naive T cells), and in part to alterations of function within the different T lymphocyte subsets. We show that the fluorochrome rhodamine-123 (R123) can distinguish further subdivisions within the naive and memory populations of both CD4 and CD8 T cells in the mouse. Aging leads to a progressive increase in the proportion of T cells in each subset that stain dimly with R123, and a corresponding decrease in the proportion of R123hi T cells, which are typical in young mice. We show that differential R123 staining between T cell subsets is due to variation in the activity of P-glycoprotein (P-Gp), the 170 kDa, ATP-dependent plasma membrane pump that mediates multiple-drug resistance. All T cells initially take up equivalent amounts of R123, but some T cells then can extrude the dye in a temperature-dependent process that is blocked by each of four pharmacologically disparate inhibitors of P-Gp function. Immunofluorescence experiments suggest that T cells from old and young mice have equal amounts of the P-Gp molecule itself, suggesting that differences in R123 extrusion may depend on posttranslational regulation of P-Gp activity.
pubmed_641_17500
pubmed_235_20405
Toxoplasma gondii seroprevalence have been rapidly increasing in some parts of Korea. We analyzed prevalence of anti-Toxoplasma gondii antibodies, using a rapid diagnostic test (RDT), in the sera of 552 residents in Ganghwa-gun, 661 ones in Cheorwon-gun, and 305 ones in Goseong-gun, Korea in 2019. IgG/IgM RDT mounted with recombinant fragment of major surface antigen (SAG1), glutathione-S-transferase-linker-SAG1A, were applied to the sera. IgG seroprevalence was 28.1% in Ganghwa-gun, 19.5% in Cheorwon-gun and 35.7% in Goseong-gun. Odds ratios comparing Cheorwon vs Ganghwa was 0.63 (P=0.001) and Goesong versus Ganghwa was 1.47 (P=0.01) adjusting age and sex. Goseong had highest seroprevalence among the 3 counties both in crude rates and logistic regression. Although Cheorwon and Goseong are adjacent to the demilitarized zone (DMZ) in Korea, seroprevalence rate was much higher in Goseong. Further investigation on other DMZ-closed areas is necessary whether they have high prevalence rates compared to the other areas. T. gondii prevalence in Korea is still persists; proper health policy should be established.
10.3347/kjp.2021.59.1.9
pubmed_448_6579
Quantifying the level of linkage disequilibrium (LD), non-random association of alleles at two or more loci, is important to determine the number of markers needed for genomic selection. The aims of this study were to evaluate the extent of LD in Dual-Purpose Belgian Blue (DPBB) and to compare the level of LD in DPBB with that of Walloon Holstein. Data of 28,427 single nucleotide polymorphisms (SNP), located on 29 Bos taurus autosomes (BTA), of 639 DPBB and 398 Holstein bulls were used. The level of LD between pairwise SNPs separated by up to 10 Mb was evaluated, separately for each breed, using the squared correlation of the alleles at two loci. The analysis of molecular variance showed that the percentage of variation within populations (85.48%) was higher than between populations (14.52%). However, permutation tests showed a significant genetic differentiation between the two studied populations (p < .01). The average LD found between adjacent SNP pairs in DPBB (0.16 (SD = 0.22)) was generally lower than in Holstein (0.23 (SD = 0.27)). The proportion of SNPs in useful LD (r2  > 0.30) within a genomic distance of ≤0.10 Mb between SNPs was 18.58% and 28.23% in DPBB and Holstein bulls, respectively. In both breeds, the effective population size decreased over generations; however, the decline was greater in DPBB than that in Holstein. Based on results, it can be concluded that at least 68,000 SNPs are needed for implementing genomic selection in DPBB cattle with enough accuracy.
10.1111/jbg.12662
pubmed_1124_6480
Genetic disorders of the skeleton (skeletal dysplasias and dysostoses) are a large and disparate group of diseases whose unifying features are malformation, disproportionate growth, and deformation of the skeleton or of individual bones or groups of bones. To cope with the large number of different disorders, the "Nosology and Classification of the Osteochondrodysplasias," based on clinical and radiographic features, has been designed and revised periodically. Biochemical and molecular features have been partially implemented in the Nosology, but the rapid accumulation of knowledge on genes and proteins cannot be easily merged into the clinical-radiographic classification. We present here, as a complement to the existing Nosology, a classification of genetic disorders of the skeleton based on the structure and function of the causative genes and proteins. This molecular-pathogenetic classification should be helpful in recognizing metabolic and signaling pathways relevant to skeletal development, in pointing out candidate genes and possible therapeutic targets, and more generally in bringing the clinic closer to the basic science laboratory and in promoting research in this field.
pubmed_1124_6480
pubmed_972_6440
A recent study by Feng et al. [Feng S, Krueger A, Oppenheimer M (2010) Proc Natl Acad Sci USA 107:14257-14262] in PNAS reported statistical evidence of a weather-driven causal effect of crop yields on human migration from Mexico to the United States. We show that this conclusion is based on a different statistical model than the one stated in the paper. When we correct for this mistake, there is no evidence of a causal link.
10.1073/pnas.1202049109
pubmed_250_7049
High-resolution polymerase chain reaction sequence-specific primer typing and sequence-based typing of the human leukocyte antigen (HLA) gene DRB1 in a potential hematopoietic stem cell donor of Kurdish ethnicity revealed a new allelic variant of HLA-DRB1*11. The sequence was named DRB1*1167, and comparison with previously described DRB1 alleles demonstrated a mixed pattern shared with some DRB1*08 alleles.
10.1111/j.1399-0039.2008.01163.x
pubmed_1044_18021
Nonlinear correlation exists in many types of biomedical data. Several types of pairwise gene expression in humans and other organisms show nonlinear correlation across time, e.g., genes involved in human T helper (Th17) cells differentiation, which motivated this study. The proposed procedure, called Kernelized correlation (Kc), first transforms nonlinear data on the plane via a function (kernel, usually nonlinear) to a high-dimensional (Hilbert) space. Next, we plug the transformed data into a classical correlation coefficient, e.g., Pearson's correlation coefficient (r), to yield a nonlinear correlation measure. The algorithm to compute Kc is developed and the R code is provided online. In three simulated nonlinear cases, when noise in data is moderate, Kc with the RBF kernel (Kc-RBF) outperforms Pearson's r and the well-known distance correlation (dCor). However, when noise in data is low, Pearson's r and dCor perform slightly better than (equivalently to) Kc-RBF in Case 1 and 3 (in Case 2); Kendall's tau performs worse than the aforementioned measures in all cases. In Application 1 to discover genes involved in the early Th17 cell differentiation, Kc is shown to detect the nonlinear correlations of four genes with IL17A (a known marker gene), while dCor detects nonlinear correlations of two pairs, and DESeq fails in all these pairs. Next, Kc outperforms Pearson's and dCor, in estimating the nonlinear correlation of negatively correlated gene pairs in yeast cell cycle regulation. In conclusion, Kc is a simple and competent procedure to measure pairwise nonlinear correlations.
10.1371/journal.pone.0270270
pubmed_472_12213
BACKGROUND Lung cancer symptoms are vague and difficult to detect. Interventions are needed to promote early diagnosis, however health services are already pressurised. This study explored symptomology and help-seeking behaviours of primary care patients at 'high-risk' of lung cancer (≥50 years old, recent smoking history), to inform targeted interventions. METHODS Mixed method study with patients at eight general practitioner (GP) practices across south England. Study incorporated: postal symptom questionnaire; clinical records review of participant consultation behaviour 12 months pre- and post-questionnaire; qualitative participant interviews (n = 38) with a purposive sample. RESULTS A small, clinically relevant group (n = 61/908, 6.7%) of primary care patients was identified who, despite reporting potential symptoms of lung cancer in questionnaires, had not consulted a GP ≥12 months. Of nine symptoms associated with lung cancer, 53.4% (629/1172) of total respondents reported ≥1, and 35% (411/1172) reported ≥2. Most participants (77.3%, n = 686/908) had comorbid conditions; 47.8%, (n = 414/908) associated with chest and respiratory symptoms. Participant consulting behaviour significantly increased in the 3-month period following questionnaire completion compared with the previous 3-month period (p = .002), indicating questionnaires impacted upon consulting behaviour. Symptomatic non-consulters were predominantly younger, employed, with higher multiple deprivation scores than their GP practice mean. Of symptomatic non-consulters, 30% (18/61) consulted ≤1 month post-questionnaire, with comorbidities subsequently diagnosed for five participants. Interviews (n = 39) indicated three overarching differences between the views of consulting and non-consulting participants: concern over wasting their own as well as GP time; high tolerance threshold for symptoms; a greater tendency to self-manage symptoms. CONCLUSIONS This first study to examine symptoms and consulting behaviour amongst a primary care population at 'high- risk' of lung cancer, found symptomatic patients who rarely consult GPs, might respond to a targeted symptom elicitation intervention. Such GP-based interventions may promote early diagnosis of lung cancer or other comorbidities, without burdening already pressurised services.
10.1371/journal.pone.0165677
pubmed_942_12347
Geodesic spline interpolation is a simple and efficient approach for landmark matching by nonambiguous mappings (diffeomorphisms), combining classic spline interpolation and flows of diffeomorphisms. Here, we extend the method to incorporate the estimation of a affine transformation, yielding a consistent and numerically stable algorithm. A theoretical justification is provided by studying the existence of the global minimum of the energy.
10.1109/tip.2005.864163
pubmed_631_17672
BACKGROUND Fine-needle aspiration cytology (FNAC) is an important and useful investigation, and is considered next to imaging in the rapid diagnosis of pulmonary mass lesion for the last few decades. AIMS To assess the role of Computed Tomogram (CT) guided FNAC in pulmonary mass lesions; to analyze the results; and to compare with histopathological findings. MATERIALS AND METHODS The clinical, radiological, and cytological data of 130 patients were prospectively studied who underwent CT guided FNAC from October 2009 through September 2011. Thereafter these patients underwent bronchoscopic/trucut biopsy/lobectomy, whatever clinically indicated. Smears and tissue sections were evaluated simultaneously to reach at a definite diagnosis. RESULTS Out of 130 cases, we found adequate FNAC smear and histopathology reports only in 124 cases. The age range varied from 35 to 73 years with the peak in the fifth to sixth decades. The benign lesions were 10 (8.07%) and malignant lesions were114 (91.93%) shown by cytology. The most common tumor was adenocarcinoma (51.72%) followed by squamous cell carcinoma (22.41%) and small cell carcinoma 6.89%. Diagnostic accuracy of CT guided FNAC was 95%. Post procedural complications such as hemorrhage and chest pain were minimal and were noted only in three cases. CONCLUSION CT guided FNAC of pulmonary masses provides simple, easy, and reliable method for reaching rapid tissue diagnosis with minimal complication.
10.4103/2278-330X.105881
pubmed_935_14032
1. D-Galactosamine-HCl induces toxic hepatitis in the rat and was used as a model to study some aspects of iron metabolism during liver cell damage. Some changes in iron metabolism were similar to those encountered in human acute viral hepatitis. 2. During the first 3 days of liver cell damage induced by galactosamine, liver depot iron and especially ferritin iron decreased by approximately 20%. Plasma ferritin rose, with a peak mean value which was approximately 20 times the concentration measured in normal rats. 3. During the acute phase, plasma ferritin did not accurately reflect the change in the level of liver depot iron. 4. During and after the acute phase, liver depot iron increased after an initial decrease. The non-ferritin depot iron fraction was elevated approximately 75% compared with the value in normal rats. This increase in non-ferritin iron was probably caused by increased erythrocyte catabolism in the liver and recapture followed by catabolism of liver ferritin that had leaked into the blood.
10.1042/cs0580321
pubmed_877_23785
Lantibiotics are ribosomally produced and posttranslationally modified peptides containing several lanthionine residues. They exhibit substantial antimicrobial activity against Gram-positive bacteria, including relevant pathogens. The production of the model lantibiotic nisin minimally requires the expression of the modification and export machinery. The last step during nisin maturation is the cleavage of the leader peptide. This liberates the active compound and is catalyzed by the cell wall-anchored protease NisP. Here, we report the production and purification of a soluble variant of NisP. This has enabled us to study its specificity and test its suitability for biotechnological applications. The ability of soluble NisP to cleave leaders from various substrates was tested with two sets of nisin variants. The first set was designed to investigate the influence of amino acid variations in the leader peptide or variations around the cleavage site. The second set was designed to study the influence of the lanthionine ring topology on the proteolytic efficiency. We show that the substrate promiscuity is higher than has previously been suggested. Our results demonstrate the importance of the arginine residue at the end of the leader peptide and the importance of lanthionine rings in the substrate for specific cleavage. Collectively, these data indicate that NisP is a suitable protease for the activation of diverse heterologously expressed lantibiotics, which is required to release active antimicrobial compounds.
10.3389/fmicb.2018.00160
pubmed_548_6664
Tendinopathy is a critical clinical problem as it is often asymptomatic at onset and during development, and is only recognized upon rupture of the tendon. It is common among recreational and competitive athletes. The present study sought to examine the molecular mechanism of the progression of tendinopathy by screening out differentially expressed genes (DEGs) and investigating their functions. In addition, the present study aimed to identify the small molecules, which exhibit potential effects, which could be utilized for the treatment of tendinopathy. The gene expression profile of tendinopathy, GSE26051 was downloaded from the Gene Expression Omnibus database, which included 23 control samples and 18 samples of tendinopathy. The DEGs were identified using the Limma package in the R programming language, and gene ontology and pathway enrichment analysis were performed. In addition, the potential regulatory microRNAs and the target sites of the transcription factors were screened out based on the molecular signature database. In addition, the DEGs were mapped to the connectivity map database to identify the potential small molecule drugs. A total of 318 genes were filtered as DEGs between diseased samples and normal control tendons. Additionally, genes, including laminin, α4, platelet‑derived growth factor α, laminin γ1 and Src homology 2 transforming protein 1 may induce tendinopathy through the focal adhesion pathway. Furthermore, the transcription factor, lymphoid enhancer‑binding factor 1 and its target genes, pantothenate kinase 2 and G protein‑coupled receptor kinase 5 were identified. The most significant microRNA, miR‑499, was screened and was found to regulate specific genes, including CUGBP2 and MYB. Additionally, the small molecules, Prestwick‑1082 and viomycin were identified to have the potential to repair disordered metabolic pathways and furthermore to remedy tendinopathy. The results of the present study assessed the mechanism of tendinopathy and screened small molecule drugs as potential treatments for this condition. In addition, the present findings have the potential for use in a clinical setting for the treatment of tendinopathy in the future.
10.3892/mmr.2014.3081
pubmed_840_6296
Reunion Island is a French province, 800 km east of Madagascar and 200 km west of Mauritius. On Reunion Island, the birth prevalence of cystic fibrosis (CF) is particularly high in the population of European origin, approximately 1:1000. In a previous study, we demonstrated that the screening of the 27 exons of the CF transmembrane conductance regulator (CFTR) gene by denaturing high-pressure liquid chromatography (DHPLC) in 114 CF families allowed the detection of about 93% of the molecular defects present on Reunion Island. Unidentified CF mutations may lie in introns or in regulatory regions that are not routinely investigated, or may correspond to gene rearrangements such as large, heterozygous deletions that escape detection using current PCR-based techniques. Using a combination of different methods (such as multiplex ligation-dependent probe amplification), 6 of the 13 unidentified CF alleles (46%) were found to harbor a deletion of 5288 bp, spanning from exon 17a to 18. Identification and examination of the breakpoint sequences showed that this deletion is different from the 3120+1kbdel8.6Kb previously found in the Palestinian Arabs. The chromosomes bearing IVS16+3316_IVS18+644del5288 did not have a common extragenic haplotype. Clinical evaluation of homozygotes (2 unrelated patients) and compound heterozygotes indicated that this deletion represents a severe mutation associated with positive sweat chloride test, pancreatic insufficiency, and early age at diagnosis.
10.1089/gte.2006.10.208
pubmed_1069_20195
During compensatory cardiac hypertrophy in the rat, hemodynamic overload induces a parallel decrease in the densities of both beta 1-adrenergic (beta 1-AR) and M2-muscarinic (M2-MR) receptors in the left ventricle, but the total number of receptors remains unchanged. It is not known whether this reduction is transcriptionally or translationally regulated, or if the functionally closely linked alpha-subunits of G protein (G alpha s and G alpha i-2) partake in this regulation. In order to resolve these questions, the absolute concentrations of mRNAs for both receptors and for G alpha s and G alpha i-2 were quantified by slot blot analysis of the left ventricles of adult rats 5 weeks after aortic banding. The results showed a significant decrease of both receptor mRNA levels in hypertrophied left ventricle (beta 1-AR: -48%; M2-MR: -42%) that paralleled the reduction in receptor protein densities and was negatively correlated with the left ventricular weight/body weight ratio (LVW/BW). By contrast, the relative levels of G alpha s and G alpha i-2 mRNAs remained unchanged, and both accumulated proportionally to the increase in LVW/BW. These results show that the beta 1-AR and the M2-MR were pretranslationally regulated. This suggests the hypothesis that the corresponding genes do not follow the general increase in transcriptional activity. By contrast, the genes coding for G alpha s and G alpha i-2 may follow the general pattern of activation during hypertrophy. Receptors and coupling proteins belong to two different groups of genes that are controlled by distinct mechanisms of regulation.
10.1016/s0022-2828(95)91767-5
pubmed_454_4790
Cyclopeptides are an important class of substances in nature, and their physiological effects are frequently based on the tendency to form bioactive conformations. Therefore the investigation of their structure yields an understanding of their functionalities. Mass-selective combined IR/UV spectroscopy in molecular beam experiments represents an ideal tool for structural analyses on isolated molecules in the gas phase, such as the investigated cyclo[L-Tyr(Me)-D-Pro](2) peptide and its complexes with water. Using the chosen spectroscopic method in combination with DFT calculations, an assignment of a structure with two intramolecular hydrogen bonds for the naked cyclopeptide is possible. For the monohydrated cluster two isomers have to be discussed: in one of them the water molecule is simply attached to the assigned monomer structure as hydrogen donor, whereas the second isomer can be characterized by a water molecule that is inserted into one of the intramolecular hydrogen bonds.
10.1002/cphc.201001055
pubmed_614_13604
INTRODUCTION The tandem-repeat type galectins, which comprise of gal-4, -6, -8, -9, and -12, form a sub-family of galectins. Gal-6 is expressed only in rodents, whereas the other four galectins, tandem-repeat galectins, are also detectable in human tissue. The placental expression of individual members of the tandem-repeat gal family is increasingly known, however, systematic, comparative analysis especially in the human placenta from normal or pathological pregnancies is still lacking. MATERIAL AND METHODS Within this study, third trimester placentas obtained at delivery (n = 14 IUGR, n = 15 controls, equally divided in placentas from male and female fetuses) were analyzed for the expression of gal-4, -8, -9 and -12 by immunohistology and immunofluorescence, data were obtained by using a semiquantitative scoring system. Double immune-fluorescence with trophoblast specific markers was used to identify co-expression in the decidua. RESULTS We identified dysregulation of tandem repeat galectins in IUGR placentas with a strong connection to the fetal gender. We identified a significantly lower expression of gal-4 and gal-9 in villous trophoblast tissue of IUGR placentas with male fetuses and a downregulation of gal-4 and gal-8 in extravillous trophoblast (EVT) from IUGR and male fetuses. Conversely, expression of gal-9 and gal-12 was higher in EVT of IUGR cases in placentas with female fetuses. Double immunofluorescence using cytokeratin-7 confirmed the expression of tandem-repeat galectins in EVT. DISCUSSION AND CONCLUSION The human placenta expresses tandem-repeat type galectins in villous trophoblasts, EVT, endothelial cells and decidual stromal cells. Summarizing all effects, there is significant down-regulation of gal-4, -8 and gal-9 in the IUGR trophoblast of male fetuses. In contrast, in IUGR pregnancies with female fetus gal-9 and gal-12 are upregulated in the EVT and in endothelial cells in the cases of gal-12. Therefore we propose a fetal-gender specific action of tandem repeat galectins in IUGR placentas.
pubmed_614_13604
pubmed_213_17924
Luteinizing hormone (LH) stimulates the formation of adenosine 3',5'-cyclic monophosphate (cAMP) and inositol trisphosphate (IP3) in rat granulosa cells. This report describes the effects of protein kinase C activators on second messenger generation in isolated rat granulosa cells. The protein kinase C activator 12-O-tetradecanoylphorbol 13-acetate (TPA) completely inhibited LH-stimulated inositol phosphate accumulation. The inhibitory effects of TPA were rapid (5-15 min) and concentration dependent with 50 nM TPA producing maximally inhibitory effects. However 30-min incubations with 10-100 nM TPA had no effect on LH-stimulated cAMP or progesterone levels. The inhibitory effect of TPA could not be overcome by high concentrations of LH. TPA also inhibited gonadotropin-releasing hormone-stimulated phospholipase C activity, although to a much lesser extent. Increased inositol phosphate degradation and reduced inositol phospholipid synthesis were unlikely explanations for the effects of TPA. The results indicate that phorbol esters modulate the inositol phospholipid-phospholipase C transmembrane signaling system in rat granulosa cells. The results suggest that phorbol esters may alter the coupling of the hormone receptor complex to phospholipase C.
10.1152/ajpendo.1989.256.3.E368
pubmed_322_18187
The application of cells as carriers to encapsulate chemotherapy drugs is of great significance in antitumor therapy. The advantages of reducing systemic toxicity, enhancing targeting and enhancing the penetrability of drugs to tumor cells make it have great potential for clinical application in the future. Many studies and advances have been made in the encapsulation of drugs by using erythrocytes, white blood cells, platelets, immune cells and even tumor cells. The results showed that the antitumor effect of cell encapsulation chemotherapy drugs was better than that of single chemotherapy drugs. In recent years, the application of cell-based vectors in cancer has become diversified. Both chemotherapeutic drugs and photosensitizers can be encapsulated, so as to achieve multiple antitumor effects of chemotherapy, photothermal therapy and photodynamic therapy. A variety of ways of coordinated treatment can produce ideal results even in the face of multidrug-resistant and metastatic tumors. However, it is regrettable that this technology is only used in vitro for the time being. Standard answers have not yet been obtained for the preservation of drug-loaded cells and the safe way of infusion into human body. Therefore, the successful application of drug delivery technology in clinical still faces many challenges in the future. In this paper, we discuss the latest development of different cell-derived drug delivery systems and the challenges it will face in the future.
10.1186/s11671-021-03588-x
pubmed_807_14206
It has long been believed that cerebral lesions were irreversible in the adult human brain. However, the spontaneous improvement in functional outcome observed in the following weeks after cerebral ischemia suggests plasticity phenomenons involving postischemic neuronal network reorganization. Regarding the large prevalence of stroke in industrialized countries, and the few available treatments, the understanding of cerebral plasticity has become an important issue but also a potential source of new therapeutic approaches in stroke. Thus, "constraint induced therapy" and repetitive transcranial magnetic stimulation (rTMS) are based on the concept of local but also remote consequences of the ischemic focal lesion. Cell-therapy is based on the capacity of stem cells to respond to hypoxic signals and adapt their phenotype to the host organ, but above all to release cytokines locally and boost endogeneous repair mechanisms. We could consider to perform in the future a sequential treatment with fibrinolysis, stem cell therapy, repetitive transcranial magnetic stimulation and constraint-induced therapy in the same patient.
10.1016/j.revmed.2009.08.014
pubmed_644_291
OBJECTIVE The aim of this survey was to identify all the publicly funded memory clinics in the 21 District Health Boards (DHBs) in New Zealand. METHOD Information on the provision of memory clinics was obtained by emailing the old age psychiatrists' group and making telephone contact with clinicians working in old age psychiatry/geriatric services. A brief structured questionnaire was completed by the memory clinic lead clinicians. RESULTS There are eight memory clinics in New Zealand, funded equally between mental health services and geriatric medicine. However, there is variability in the provision of memory clinics in the medium and smaller sizedDHBs and inconsistency in the level of funded staff across DHBs. CONCLUSIONS Acknowledgement of the value of memory clinics within a national service framework is needed, with appropriate benchmarking of funding. This would ensure improved access, including for rural and remote areas of New Zealand.
10.1080/10398560701852131
pubmed_1036_4965
OBJECTIVE To evaluate the diagnostic significance of multiple detector-row spiral CT(MSCT) in patients with obstructive sleep apnea hypopnea syndrome (OSAHS). METHOD Sixty-seven patients with OSAHS and 40 volunteers were scanned. The CT imagings from the nasopharyngeal floor to the glottis obtained. The relevant dimensions of area, diameter, thickness of retropharyngeal tissue were measured in some regions in imagings including nasopharynx, oral pharynx and hypopharynx, as well as the narrowest region in pharynx. RESULT 1) The values of area, left-right diameter and front-back diameter of oral pharyngeal imagings of patients with OSAHS were narrowest regions which were (133.5 +/- 32. 9) mm2, (12.5 +/- 2.0) mm, (10.4 +/- 1.8) mm respectively. The value of above parameters of oral pharyngeal imagings of volunteers were (238.5 +/- 46.5) mm2, (20.4 +/- 3.1) mm, (21.1 +/- 4.0) mm respectively. The values of two groups had marked difference by statistics (P< 0.01). 2) The narrowest regions were located in oral pharynx in the imagings of 58 patients with OSAHS, which located in soft palate site in 19 patients, in oral pharynx site in 11 patients and in retro-lingua site in 28 patients. The narrowest regions were located in nasopharynx in the imagings of 3 patients. None of the narrowest region was found in hypopharynx. The narrowest regions, which all located in oral pharynx, were measured in the imagings of 24 volunteers. 3) The values of area, left-right and front-back diameter of the narrowest regions of imaging of 58 patients with OSAHS among 67 patients were (75.6 +/- 17.9) mm2, (10.6 +/- 2.1) mm, (6.9 +/- 1.0) mm respectively. The values of bove parameter of the most narrowest regions of imagings of volunteer were (187.3 +/- 35.6) mm2, (21.4 +/- 4.3) mm, (15.6 +/- 2.7) mm respectively. There were significant difference in statistics among the data of these groups (P < 0.01). CONCLUSION The imagings of MSCT may provide accurate diagnosis in OSAHS. Patients with OSAHS always had anatomically narrow in pharynx, especially in oral pharynx.
pubmed_1036_4965
pubmed_898_24422
A human organism depends on stable glucose blood levels in order to maintain its metabolic needs. Glucose is considered to be the most important energy source, and glycolysis is postulated as a backbone pathway. However, when the glucose supply is limited, ketone bodies and amino acids can be used to produce enough ATP. In contrast, for the functioning of the pentose phosphate pathway (PPP) glucose is essential and cannot be substituted by other metabolites. The PPP generates and maintains the levels of nicotinamide adenine dinucleotide phosphate (NADPH) needed for the reduction in oxidized glutathione and protein thiols, the synthesis of lipids and DNA as well as for xenobiotic detoxification, regulatory redox signaling and counteracting infections. The flux of glucose into a PPP-particularly under extreme oxidative and toxic challenges-is critical for survival, whereas the glycolytic pathway is primarily activated when glucose is abundant, and there is lack of NADP+ that is required for the activation of glucose-6 phosphate dehydrogenase. An important role of glycogen stores in resistance to oxidative challenges is discussed. Current evidences explain the disruptive metabolic effects and detrimental health consequences of chronic nutritional carbohydrate overload, and provide new insights into the positive metabolic effects of intermittent fasting, caloric restriction, exercise, and ketogenic diet through modulation of redox homeostasis.
10.3390/antiox9020140
pubmed_582_1941
The first laparoscopic sliding knot to be described was the Roeder knot; it has been used for a variety of procedures in all surgical disciplines. It was surmised that the introduction of new modifications in the geometry of the knot paralleled the introduction of its new indications, and that not all modifications improved its security. Therefore, a geometrical review was made of all modifications and all data on knot security and loop security of the knot were analyzed. The introduction of the original knot and its 14 applicable modifications paralleled the increase in minimally invasive techniques and the spread of these techniques in all the medical specialties. Roeder loop security depends predominantly on the number of initial turns around the standing part. Its knot security depends on the additional half hitches used to backup the knot after it has been tightened. Only a few of the modifications improved the security of the knot or its previous modifications.
10.1097/SLE.0b013e3181572b00
pubmed_723_18090
Latent class models have become a popular means of summarizing survey questionnaires and other large sets of categorical variables. Often these classes are of primary interest to better understand complex patterns in data. Increasingly, these latent classes are reified into predictors of other outcomes of interests, treating the most likely class as the true class to which an individual belongs even though there is uncertainty in class membership. This uncertainty can be viewed as a form of measurement error in predictors, leading to bias in the estimates of the regression parameters associated with the latent classes. Despite this fact, there is very limited literature treating latent class predictors as measurement error models. Most applications ignore this issue and fit a two-stage model that treats the modal class prediction as truth. Here, we develop two approaches-one likelihood-based, the other Bayesian-to implement a joint model for latent class analysis and outcome prediction. We apply these methods to an analysis of how acculturation behaviors predict depression in South Asian immigrants to the United States. A simulation study gives guidance for when a two-stage model can be safely implemented and when the joint model may be required.
10.1097/EDE.0000000000001139
pubmed_576_9260
A new low-frequency ultrasonic device (50-100 kHz) in highly sharpened end sensors that behave as point sources were examined. The application of this new ultrasonic technique with two sensors coupled in the near field is to explore the relations between the physical properties measured through the evolution of the wave time of flight and structural changes during gel formation which is related to two factors: the ambient temperature and the mechanical resistance of the medium. The network evolution was interpreted by an approach based on the Flory model. The physical significance of this model was shown through a series of experiments using a low-frequency ultrasonic technique. Response curves demonstrate the different stages during gel formation.
10.1121/1.428659
pubmed_950_25551
BACKGROUND This study examined the associations of single-nucleotide polymorphisms in the interleukin-6 receptor gene (Asp358 A>C) and the interleukin-6 promoter (-174G>C and -597G>A) with interleukin-6 levels and postoperative atrial fibrillation (POAF) after coronary artery bypass grafting (CABG). METHODS The study enrolled 371 Chinese Han patients who were undergoing CABG. Serum interleukin-6 levels were measured preoperatively and at 6, 12, and 18 hours postoperatively. Genotypes for the 3 polymorphisms were determined. RESULTS Overall, POAF developed in 30.2% of patients. The CC genotype and C allele frequencies for the interleukin-6 receptor Asp358 A>C polymorphism were significantly higher in patients with POAF than in patients without POAF (P = .003), and the interleukin-6 levels were significantly higher in patients with the CC genotype compared with A allele carriers at 6, 12, and 18 hours in the overall cohort and at 12 and 18 hours in the POAF subgroup, but there were no significant differences in the non-POAF subgroup. However, the allele and genotype frequencies of the interleukin-6 -174G>C and -597G>A polymorphisms were similar among groups, and there were no differences in interleukin-6 levels at any time point between the C/A allele carriers and the patients with GG genotypes. Univariate analysis showed that the CC genotype for interleukin-6 receptor Asp358 A>C, age, and history of cerebrovascular disease were associated with POAF. Multivariable regression showed that the CC genotype was independently related to the development of POAF (odds ratio, 2.01; 95% confidence interval: 1.15 to 3.52; P = .014). CONCLUSIONS The interleukin-6 receptor Asp358 A>C polymorphism may contribute to genetic susceptibility to POAF after CABG.
10.1016/j.athoracsur.2020.04.123
pubmed_1125_1905
The worldwide pandemic of human immunodeficiency virus (HIV) casts its shadow on childbirth, especially in developing countries, where the estimated rate of vertical transmission is 15%-40%, compared with 15%-25% in developed countries. To date, a total number of 90 children younger than 12 years of age are infected with the virus in Israel, and during the years 2001-2003, an average of 29 mothers living with AIDS gave birth annually. Mother-to-child transmission (MTCT) of HIV can occur during pregnancy, in the intrapartum period or postnatally, through breastfeeding. One third of all the breastfed newborn acquire the infection postnatally. HIV can penetrate through the damaged gastrointestinal mucosa into the newborn blood system. Risk increases during gastrointestinal infections and oral skin lesions. MTCT rate is 3.2 to 100 child years, especially if the mother is infected just before or after labor. Antiretroviral therapy during pregnancy and labor, and throughout the first 6 weeks of life in newborn may reduce MTCT by 3-folds. Further avoidance of breastfeeding lowers MTCT to 1%-2%. Most HIV infected women who gave birth in Israel originated from endemic countries. As breastfeeding is the preferred option in traditional cultures, early waning and alternative strategy of supplying substitutes is unique. This recommendation should be combined with medical follow-up for both the mother and her offspring, as well as psychosocial intervention, if needed.
pubmed_1125_1905
pubmed_572_13101
The precise diagnostic tests and subsequent prognostic stratification for patients with myelodysplastic syndrome (MDS) are often cumbersome, yet they are the basis of successful therapy. Diverse treatment options are available for these patients; however, the decisions in real-life are often not grounded on the available evidence. Although the International Prognostic Scoring System and revised International Prognostic Scoring System are still driving the medical approach to MDS patients, additional variables must be considered when therapeutic intervention is needed. A rational scheme for first-line therapy is described that allows for the possibility of selecting the optimal individual therapy for MDS patients.
10.1016/j.clml.2017.02.013
pubmed_467_21614
Transcription is of the most crucial steps of gene expression in bacteria, whose regulation guarantees the bacteria's ability to adapt to varying environmental conditions. Discovering the molecular basis and genomic principles of the transcriptional regulation is thus one of the most important tasks in cellular and molecular biology. Here, a comprehensive phylogenetic footprinting framework was implemented to predict maximal regulons of Lactococcus lactis subsp. lactis IO-1, a lactic acid bacterium known for its high potentials in nisin Z production as well as efficient xylose consumption which have made it a promising biotechnological strain. A total set of 321 regulons covering more than 90% of all the bacterium's operons have been elucidated and validated according to available data. Multiple novel biologically-relevant members were introduced amongst which arsC, mtlA and mtl operon for BusR, MtlR and XylR regulons can be named, respectively. Moreover, the effect of riboflavin on nisin biosynthesis was assessed in vitro and a negative correlation was observed. It is believed that understandings from such networks not only can be useful for studying transcriptional regulatory potentials of the target organism but also can be implemented in biotechnology to rationally design favorable production conditions.
10.1038/s41598-020-59731-8
pubmed_598_1464
BACKGROUND Primary brain tumours newly affect >260 000 people each year worldwide. In the UK, every year >10 000 people are diagnosed with a brain tumour while >5000 die annually from the disease. Prognoses are poor, cognitive deterioration common and patients have prolonged palliative needs. Advance care planning (ACP) may enable early discussion of future care decisions. Although a core commitment in the UK healthcare strategy, and the shared responsibility of clinical teams, ACP appears uncommon in practice. Evidence around ACP practice in neuro-oncology is limited. OBJECTIVES We aimed to elicit key social and structural conditions contributing to the avoidance of ACP in neuro-oncology. DESIGN A cross-sectional qualitative study design was used. SETTING One tertiary care hospital in the UK. PARTICIPANTS Fifteen healthcare professionals working in neuro-oncology participated in this study, including neuro-oncologists, neurosurgeons, clinical nurse specialists, allied healthcare professionals and a neurologist. METHOD Semi-structured interviews were conducted with participants to explore their assumptions and experiences of ACP. Data were analysed thematically using the well-established framework method. RESULTS Participants recognised the importance of ACP but few had ever completed formal ACP documentation. We identified eight key factors, which we suggest comprise three main conditions for avoidance: (1) difficulties being a highly emotive, time-intensive practice requiring the right 'window of opportunity' and (2) presence and availability of others; (3) ambiguities in ACP definition, purpose and practice. Combined, these created a 'culture of shared avoidance'. CONCLUSION In busy clinical environments, 'shared responsibility' is interpreted as 'others' responsibility' laying the basis for a culture of avoidance. To address this, we suggest a 'generalists and specialists' model of ACP, wherein healthcare professionals undertake particular responsibilities. Healthcare professionals are already adopting this model informally, but without formalised structure it is likely to fail given a tendency for people to assume a generalist role.
10.1136/bmjopen-2017-019057
pubmed_1033_16587
As the elderly population increases in number, the need to integrate innovative teaching strategies in geriatric education becomes more apparent. Teaching with stories promotes knowledge and values to students and is appealing and enjoyable. This article describes a geriatric nursing course in which stories in films and literature are used to teach content and values promoted by the Hartford Institute best practices curriculum. Stories are also used for the service-learning component of the course as students participate in a "Make a Difference" project with elderly people.
pubmed_1033_16587
pubmed_122_3562
Purpose: A key factor in regulating bone absorption is the proportion of RANKL/OPG. Although many reports showing diverse transcription factors or epigenetic modification could be responsible for regulating RANKL&OPG ratio, there is still little exploration on promoter methylation status of both genes in osteoporotic bone tissues. Our aim is to investigate the changes of methylation in CpG island of these genes' promoters in patients with primary osteoporosis. Methods: The diagnosis of osteoporosis was based on the results of dual energy X-ray absorptiometry measurements. All femoral bone tissues were separated in surgeries. After extracting total RNA, we checked the relative expression levels of OPG and RANKL by quantitative real time PCR. The genomic DNA of Non-OPF (Non-osteoporotic fracture bone tissues) & OPF (osteoporotic fracture bone tissues) were treated by bisulfite modification, and methylation status of CpG sites in the CpG island of OPG/RANKL promoters were determined by DNA sequencing. Results: RANKL expression in the OPF group was significantly higher than that in Non-OPF group, and the CpG methylation status in RANKL gene promoter was significantly lower. However, for OPG, lower gene expression level and higher methylation degree were found in the OPF group. Conclusion: Our study demonstrated that DNA methylation influenced the transcriptional expression of OPG and RANKL, which probably take on a "main switch" role in pathogenesis of primary osteoporosis.
10.7150/ijms.27333
pubmed_921_11784
BACKGROUND The purpose of this paper was to describe the imaging features of intrapelvic complications of total hip arthroplasty. METHODS The clinical presentation, ultrasound, and radiographic findings of three cases were reviewed. RESULTS Intrapelvic extrusion of cement or medial migration of prosthetic hardware caused extrinsic compression of the bladder. CONCLUSION Intrapelvic complications due to the mechanical effects of total hip arthroplasty are rare but may simulate intrinsic pelvic or bladder pathology on sonography. Plain radiographs and contrast studies provide clues to the correct diagnosis.
10.1007/s002610000063
pubmed_1047_18003
A previous study of 18 primary or metastatic prostate cancers showed loss of genetic markers on chromosome 8; 10, or 16 in more than 50% of cases [Bergerheim USR et al. (1991) Genes Chromosom Cancer 3:215-220]. The small size and infiltrative nature of primary prostatic tumors have hindered efforts to assess allelic losses by traditional restriction fragment length polymorphism (RFLP)/Southern blotting methods. To improve the sensitivity and specificity of this analysis in early prostate cancer, we have amplified polymorphic microsatellite repeats by polymerase chain reaction (PCR), and have quantitated allelic imbalances with phosphor imaging technology. In this study, 63 primary prostate tumors and matched benign tissues obtained by radical prostatectomy were examined at 28 genetic loci on chromosome 8, all but five of which were located on the short arm. Twenty-nine (46%) of the 63 cases showed loss of at least one locus. Multiple adjacent loci, usually including the LPL and MSR genes in 8p22, were lost in 28 cases. In 10 of these, losses were observed at all informative loci on the p arm. In another 15 tumors, losses were restricted to subregions of the p arm by loci retained either distally toward the p terminus or proximally at the 8p12-8p21 border, or both. In three tumors, two discrete regions of loss were observed within 8p, separated by several retained loci. Allelic loss of 8p loci was associated with higher tumor grade. These data are complementary to previous reports of allelic deletions in colorectal, hepatocellular, and non-small cell lung cancers and suggest the existence of one or more pleotropic tumor suppressor genes on 8p.
10.1002/gcc.2870100302
pubmed_979_9266
Thirty-eight children with Helicobacter pylori gastritis diagnosed by histopathology, and/or bacteriological culture were treated with omeprazole, amoxicillin and clarithromycin. Follow-up endoscopy was performed in 34 children. Outcome was measured by negative histology and culture for H. pylori. Six patients were excluded. Of the 32 remaining children eradication was achieved in 75% (95% confidence interval 60-90%).
10.1080/08035259950170330
pubmed_580_10963
Silicon has a molecular mass of 28 daltons. In nature, silicon is found as silicon dioxide (silica) or in a variety of silicates (e.g., in talc or asbestos). Furthermore, silicon is present in silicones, polymerized siloxanes, which are often used as medical silicones in breast implants. Silicon exposure is associated with different systemic autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis, progressive systemic sclerosis, and vasculitis. Remarkably, silicon in silicone-filled breast implants is considered to be safe, not increasing the risk of developing autoimmune diseases. We analyzed the impact of silicone-filled breast implants on the immune system in 32 consecutive patients attending a specialized autoimmunity clinic. All 32 patients had silicone implant incompatibility syndrome and complaints fulfilling the diagnostic criteria of ASIA (autoimmune/inflammatory syndrome induced by adjuvants). Furthermore, in 17 of the 32 patients, a systemic autoimmune disease was diagnosed, and 15 of the 32 patients had an impaired humoral immune system. Patients developed symptoms and signs after long-term follow-up, suggesting that these symptoms and signs started after implant aging and/or rupture. We postulate that silicon in silicone-filled breast implants may increase the risk of developing (auto) immune diseases and immune deficiencies.
10.1007/s12026-013-8401-3
pubmed_680_21507
Purpose To identify prognostic clinical and radiologic features in patients with unresectable hepatocellular carcinoma (HCC) treated with atezolizumab plus bevacizumab. Patients and Methods Clinical and imaging records of patients with unresectable HCC were retrospectively reviewed, and baseline features were recorded. Patients' records and imaging studies were used to determine the patients' overall survival (OS) and progression-free survival (PFS). Univariate and multivariate analyses were performed to determine prognostic features. Subanalyses of treatment-naïve patients (who never received local or systemic therapy) and previously treated patients were also performed. Results Fifty-five patients were included in the final analysis, 23 (41.8%) of whom were treatment naïve. The median PFS and OS for the entire cohort were 3.0 months and 7.9 months. The 3-, 6- and 12-month OS rates were 85.5%, 79.8% and 45.7%, respectively. The 3-, 6- and 12-month PFS rates were 50.1%, 41.2% and 20.1%, respectively. On multivariate analysis, independent prognostic features for poor PFS of the entire cohort were pleural effusions (p = 0.047, HR: 6.3; CI: 1.03-38.90) and hepatic vein tumor thrombus (p = 0.005; HR: 23.37; CI: 2.63-207.67); independent prognostic features for poor OS were ascites (p = 0.008; HR: 37.37; CI: 2.53-467.64), pleural effusion (p = 0.003; HR: 110.17; CI: 5.00-2426.54), and low (<40HU) pre-contrast attenuation on CT images (p = 0.007; HR: 0.09; CI: 0.02-0.53). On subanalysis of treatment-naïve patients, the median OS and PFS were 7.4 months and 2.8 months, respectively. The 3-, 6- and 12-month PFS rates were 43.5%, 38.6% and 24.8%, respectively. Pleural effusion was the only independent poor prognostic feature (p = 0.036; HR: 206.34; CI: 1.41-30,167.58). Conclusion Independent prognostic features for survival outcomes include the presence of ascites, pleural effusions, hepatic vein tumor thrombus, and HCC with low attenuation (<40 HU) on unenhanced CT images. Although several biochemical variables were significant on univariate analysis, none were independent predictors of OS or PFS.
10.2147/JHC.S379428
pubmed_691_6253
The mutant mouse lymphoma cell line (L5178YAII), resistant to X-rays, ultraviolet light and alkylating agents, was reinvestigated in an attempt to establish the nature of the mutation. These cells were compared with P388 mouse lymphoma cells, which exhibit normal sensitivity to these mutagens. A series of studies was conducted to compare DNA alkylation and strand breakage with cell survival after exposure of the two cell lines to methylmethane sulphonate. It was found that neither the degree of alkylation nor the removal of the common alkylation products was correlated with the different sensitivities observed in these cell lines. A correlation was established between cell killing and the production of long-lived strand breaks. P388 cells were found to accumulate twice as many long-lived strand breaks compared to L5178YAII cells, at equal levels of alkylation. This suggested that long-lived strand breaks were the major toxic lesions. Further experiments indicated that these long-lived strand breaks were produced by a process consistent with excision repair. Evidence is also presented that indicates that the mutation in L5178YAII cells that is responsible for their resistance may occur in ligase activity or its associated ADP-ribosyl transferase system.
10.1242/jcs.68.1.35
pubmed_51_8162
The hypothalamic peptide orexin plays a role in many physiological systems including feeding behavior, sleep-wakefulness, reward system, stress, and nociception. In addition, it is now clear that orexin is involved in the central regulation of cardiorespiratory function. Here, we review the cardiorespiratory effects elicited by central orexin and consider the physiological role of this peptide in central cardiorespiratory control in normal and pathophysiological states. Orexin neurons are found exclusively in the hypothalamus but project to almost all brain regions including cardiorespiratory regulatory areas, where their receptors are also expressed. Administration of orexin into the nucleus tractus solitarius, rostral ventrolateral medulla, rostral ventromedial medulla, and spinal cord increases blood pressure, heart rate, and sympathetic nerve activity. Orexin neurons stimulate respiration and are sensitive to changes in pH. Orexin knockout mice have apnoeic episodes in sleep. Therefore, orexin may be a potentially important therapeutic target for the treatment of cardiorespiratory disorders.
10.1016/B978-0-12-394623-2.00009-3
pubmed_1119_20878
The term zinc finger was first used to describe a 30-residue, repeated sequence motif found in an unusually abundant Xenopus transcription factor. It was proposed that each motif is folded around a central zinc ion to form an independent minidomain and that adjacent zinc fingers are combined as modules to make up a DNA-binding domain with the modules "gripping" the DNA (hence the term finger). We now know that these proposals were correct and that these DNA-binding motifs are found in many eukaryotic DNA-binding proteins. More recently, crystal structures of three different complexes between zinc finger domains and their target DNA binding sites have revealed a remarkably simple mode of interaction with DNA. The simplicity of the zinc finger structure, and of its interaction with DNA, is a very striking feature of this protein domain. After the discovery of the zinc finger motif, patterns of potential zinc ligands have been found in several other proteins, some of which also bind to DNA. Structural studies of these domains have revealed how zinc can stabilize quite diverse protein architectures. In total, 10 such small zinc-binding domains have been studied structurally. These form a diverse collection, but each in turn has been termed a zinc finger motif-although clearly what they have in common is only their zinc-binding property, which stabilizes an apparently autonomously folded unit.
pubmed_1119_20878
pubmed_499_15688
Object Major depressive disorder (MDD) has been demonstrated to be associated with abnormalities in neural networks. However, few studies examined information flow in the salience network (SN). This study examined abnormalities in the causal connectivity between the SN and whole brain in drug-naive first-episode patients with MDD in the resting state. Methods Based on the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) diagnostic criteria, 23 drug-naive first-episode MDD patients and 20 matched healthy individuals were recruited and underwent a resting-state magnetic resonance scan. The acquired functional image data were preprocessed using resting-state functional magnetic resonance imaging (rs-fMRI) data analysis toolkit plus (RESTplus). Then, using the data processing & analysis for brain imaging (DPABI) software and a coefficient-based general component analysis method with the right anterior insula (rAI) as the region of interest (ROI), the causal connectivity of the SN with the whole brain and its correlation with cognitive and mental performance were examined in the resting state. Results (1) The MDD group showed a significantly higher Hamilton Depression Rating Scale total score and significantly higher scores for anxiety, cognitive disturbance, and block factors compared with normal controls. (2) Compared with control: from whole brain to the rAI, the MDD group showed a lower causal connectivity in the left inferior frontal gyrus; from the rAI to the whole brain, the MDD group showed a lower causal connectivity in the right cingulate gyrus, the right precuneus, and extending to paracentral lobule but higher causal connectivity in the left inferior and middle frontal gyrus. (3) In the MDD group, from rAI to the whole brain, the causal connectivity values for the right cingulate gyrus/precuneus were negatively correlated with the score of Stroop Color-Word Test A, B, and C as well as interference times. Conclusion Our results indicated disrupted causal connectivity among the default mode network (DMN), the central executive network (CEN), and SN in drug-naive first-episode MDD patients. Especially, our results suggest a unique role for rAI in the ordered or hierarchical information processing, presumed to include bottom-up and top-down reciprocal influences among the three networks in MDD.
10.3389/fpsyt.2022.858768
pubmed_158_812
Three new nitroxyl labeled derivatives of podophyllotoxin 4-6 have been synthesized and evaluated for their antitumor activity in vitro. Compounds 4-6 showed significant inhibitory activity against human nasopharyngeal carcinoma KB,lung cancer A549 and stomach carcinoma SGC-7901 cells, as well as mouse leukemia L1210 and P388 cells. Compounds 4 and 5 exhibited comparable or superior activity to clinically used etoposide (VP-16,2) in their inhibition of these cell lines.
10.1016/s0024-3205(96)00689-3
pubmed_697_11612
The use of pristine as well as structurally modified two-dimensional materials to efficiently trap and separate various harmful gases from the atmosphere is an intensively explored field of current research. In this paper, we have computationally demonstrated the efficient trapping of several polar poisonous and greenhouse gases on top of different kinds of pyridinic/pyrrolic nitrogen-doped graphene sheets. van der Waals corrected Born-Oppenheimer molecular dynamics (BOMD) studies evidently demonstrate the trapping of the gas molecules on top of the defect-sites of the sheets at room-temperature. Importantly, the trapping of molecules does not lead to any chemical bond formation between the adsorbates and the adsorbents. Thorough investigations evidently demonstrate the formation of hydrogen-bonds between nitrogen of the adsorbents and hydrogen of the adsorbates. Furthermore, interestingly, as most abundant atmospheric gases (i.e. N2 and O2) get repealed by the defect-sites, these sheets appear to be efficient to selectively trap the pollutants from the open atmosphere. We also suggest different ways to enhance the gas-trapping capacity of these sheets, such as increasing the defect concentration, and adsorbing pollutants on both sides of the free-standing defective sheets. Finally, thermal treatment of these sheets at high temperature is demonstrated as an efficient way to recycle the adsorbent.
10.1039/c6cp06247d
pubmed_934_25168
BACKGROUND Marine diatoms constitute a major component of eukaryotic phytoplankton and stand at the crossroads of several evolutionary lineages. These microalgae possess peculiar genomic features and novel combinations of genes acquired from bacterial, animal and plant ancestors. Furthermore, they display both DNA methylation and gene silencing activities. Yet, the biogenesis and regulatory function of small RNAs (sRNAs) remain ill defined in diatoms. RESULTS Here we report the first comprehensive characterization of the sRNA landscape and its correlation with genomic and epigenomic information in Phaeodactylum tricornutum. The majority of sRNAs is 25 to 30 nt-long and maps to repetitive and silenced Transposable Elements marked by DNA methylation. A subset of this population also targets DNA methylated protein-coding genes, suggesting that gene body methylation might be sRNA-driven in diatoms. Remarkably, 25-30 nt sRNAs display a well-defined and unprecedented 180 nt-long periodic distribution at several highly methylated regions that awaits characterization. While canonical miRNAs are not detectable, other 21-25 nt sRNAs of unknown origin are highly expressed. Besides, non-coding RNAs with well-described function, namely tRNAs and U2 snRNA, constitute a major source of 21-25 nt sRNAs and likely play important roles under stressful environmental conditions. CONCLUSIONS P. tricornutum has evolved diversified sRNA pathways, likely implicated in the regulation of largely still uncharacterized genetic and epigenetic processes. These results uncover an unexpected complexity of diatom sRNA population and previously unappreciated features, providing new insights into the diversification of sRNA-based processes in eukaryotes.
10.1186/1471-2164-15-698
pubmed_355_3749
This paper studies the familial association of neonatal mortality in Matlab, Bangladesh and its relationship to birth-spacing effects on mortality. Findings show that familial association is strongest for siblings of adjacent birth orders. Moreover, birth-spacing effects on neonatal mortality are stronger when the preceding child has survived the neonatal period than when it has died. Transitional (Markov), random-effects, and marginal models for correlated data are introduced, and are contrasted in interpretation and technique. Familial association of neonatal mortality can be approximately well by a first-order Markov model using generalized estimating equations (GEE) to allow for higher-order correlation.
pubmed_355_3749
pubmed_939_3137
In this work, a series of metal-organic framework (MOF)-derived CoPd nanoalloys have been prepared. The nanocatalysts exhibited excellent activities in the hydrogenation of nitroarenes and alkenes in green solvent (ethanol/water) under mild conditions (H2 balloon, room temperature). Using ZIF-67 as template for both carbon matrix and cobalt precursor coating with a mesoporous SiO2 layer, the catalyst CoPd/NC@SiO2 was smoothly constructed. Catalytic results revealed a synergistic effect between Co and Pd components in the hydrogenation process due to the enhanced electron density. The mesoporous SiO2 shell effectively prevented the sintering of hollow carbon and metal NPs at high temperature, furnishing the well-dispersed nanoalloy catalysts and better catalytic performance. Moreover, the catalyst was durable and showed negligible activity decay in recycling and scale-up experiments, providing a mild and highly efficient way to access amines and arenes.
10.1002/chem.202003640
pubmed_130_9194
Rationale: The morbidity and mortality of heart failure (HF) have been increasing rapidly in recent years. However, the molecular events that link to the phenotype of HF remain unclear. This study aimed to investigate the molecular alterations in the pathogenesis of HF induced by pressure overload. Methods: Transverse aortic constriction was conducted to generate the HF mouse model. A multi-omics study was performed, including integrative analysis of scRNA-seq, scATAC-seq, bulk ATAC-seq and miRNA-seq data. The results of omics analysis were verified by immunofluorescence staining. Results: scRNA-seq analysis identified five major cell types, which exhibits consistency with previous studies. Integrative analysis of ATAC-seq and miRNA-seq showed the alterations of gene expression in HF. Activation of genes involved in immune response at transcriptional level and perturbed expression of their upstream miRNAs confirmed the function of immune cells in the pathogenesis of HF. Analysis of scATAC-seq revealed a NO biosynthetic related gene regulation pattern in endothelial cells of failing hearts. Conclusion: We performed a multi-omics analysis, comparing the transcriptomic, miRNA expression, and chromatin accessibility profile between the HF and control mice, thus providing mechanistic insights into the pathogenesis of pressure overload-induced HF.
10.7150/thno.68232
pubmed_260_22774
Previous studies reported the presence in rat mammary tissue of a cytosolic xanthine oxidoreductase pathway for the metabolism of alcohol to acetaldehyde and hydroxyl radicals and to the microsomal biotransformation of ethanol to acetaldehyde. It was also reported that after chronic ethanol drinking stressful oxidative conditions can be observed. The present work reports that even after single doses of ethanol, given at three different levels (6.3 g kg(-1); 3.8 g kg(-1) or 0.6 g kg(-1) p.o.), acetaldehyde accumulates for prolonged periods of time in the mammary tissue to reach concentrations higher than in blood (e.g. 5.1+/-1.2 nmol g(-1) versus 0.2+/-0.1 nmol ml(-1), for 6.3 g kg(-1) dose, 6 h after intoxication). The presence in rat mammary tissue of low activities of additional enzymes able to generate acetaldehyde was established (alcohol dehydrogenase: 0.97+/-0.84 mU mg(-1) protein; CYP2E1: 1.30+/-0.12 x 10(-2) pmol 4-nitrocatechol min(-1) mg(-1) protein) and a low activity of aldehyde dehydrogenase was observed in the cytosolic, mitochondrial and microsomal fractions (0.02+/-0.04; 0.35+/-0.09 and 0.72+/-0.19 mU mg(-1) protein, respectively). After a single high dose of ethanol, an increased susceptibility to oxidative stress was observed, as evidenced by changes in the shape of t-butylhydroperoxide induced emission of chemiluminescence in mammary tissue (6.3 g kg(-1) dose; at 3 and 6 h). In summary, the results show that even after single doses of ethanol, acetaldehyde, either formed in situ or arriving via blood, tends to accumulate in mammary tissue and that this condition might decrease cell defenses against injury.
10.1002/jat.1281
pubmed_242_25122
OBJECTIVE We propose a method of identifying clinical topics for campaigns like Choosing Wisely. METHODS In the context of an ongoing continuing medication education program, we analyzed ratings on every patient-oriented evidence that matters (POEM) synopsis delivered in 2012 and 2013. Given the objective of the Choosing Wisely campaign, we focused this analysis on 1 specific item in the validated questionnaire used by physicians to rate POEMs. This questionnaire item is about "avoiding an unnecessary diagnostic test or treatment." For each POEM, we calculated frequencies and proportions for this item, then we identified the 20 POEMs that were most commonly associated with this item in 2012 and 2013. Finally, we determined whether the clinical topic of each of these POEMs was mentioned in the Choosing Wisely master list. RESULTS In 2012 and 2013 we received 506,809 completed questionnaires (or ratings) linked to 530 POEMs, for an average of 956 ratings per POEM. In 59% of these POEMs (n = 312), the most commonly expected type of health benefit was "avoiding an unnecessary diagnostic test or treatment." We then identified the top 20 POEMs most commonly associated with this item in each year by ranking all 312 POEMs from the top down. The clinical topic addressed by 29 of these 40 POEMs was not addressed in the Choosing Wisely master list. These topics fell into 3 categories: diagnostic tests, medical interventions, and surgical interventions. CONCLUSION "Big data" can identify clinical topics relevant to campaigns such as Choosing Wisely. This process represents a new way to inform the expert panel approach.
10.3122/jabfm.2015.02.140226
pubmed_49_15631
A method to prevent inguinoscrotal haematoma following hernia and hydrocele repair is presented. The technique was used in 34 consecutive patients, none of whom developed a significant postoperative haematoma or complications.
pubmed_49_15631
pubmed_188_15548
In this article, I examine group medical visits, a clinic-based intervention that aims to improve patient health by combining clinical care, health education and peer support. Research shows that health care inequalities are reproduced through the interplay of interpersonal, institutional, and structural factors. I examine changing social relations made possible by group visits, including peer support and an expanded role for patient knowledge. The qualitative data presented here are part of a mixed-methods study of how group medical visits and integrative medicine are combined and implemented for low-income people with chronic conditions. I find that patients take active roles in each other's care, supporting, challenging, and advocating in ways that shift patient-provider relationships. Such shifts demand reflection about what kinds of knowledge matter for health. Health care encounters can reproduce inequality for marginalized patients; this study suggests group visits can restructure patient-provider encounters to interrupt healthcare inequalities.
10.1177/1049732318759528
pubmed_615_24596
Acquired alterations in mitochondrial DNA are believed to play a pathogenic role in Parkinson's disease. In particular, accumulation of mitochondrial DNA deletions has been observed in substantia nigra pars compacta dopaminergic neurons from patients with Parkinson's disease and aged individuals. Also, mutations in mitochondrial DNA polymerase gamma result in multiple mitochondrial DNA deletions that can be associated with levodopa-responsive parkinsonism and severe substantia nigra pars compacta dopaminergic neurodegeneration. However, whether mitochondrial DNA deletions play a causative role in the demise of dopaminergic neurons remains unknown. Here we assessed the potential pathogenic effects of mitochondrial DNA deletions on the dopaminergic nigrostriatal system by using mutant mice possessing a proofreading-deficient form of mitochondrial DNA polymerase gamma (POLGD257A), which results in a time-dependent accumulation of mitochondrial DNA deletions in several tissues, including the brain. In these animals, we assessed the occurrence of mitochondrial DNA deletions within individual substantia nigra pars compacta dopaminergic neurons, by laser capture microdissection and quantitative real-time polymerase chain reaction, and determined the potential deleterious effects of such mitochondrial DNA alterations on mitochondrial function and dopaminergic neuronal integrity, by cytochrome c oxidase histochemistry and quantitative morphology. Nigral dopaminergic neurons from POLGD257A mice accumulate mitochondrial DNA deletions to a similar extent (∼40-60%) as patients with Parkinson's disease and aged individuals. Despite such high levels of mitochondrial DNA deletions, the majority of substantia nigra pars compacta dopaminergic neurons from these animals did not exhibit mitochondrial dysfunction or degeneration. Only a few individual substantia nigra pars compacta neurons appeared as cytochrome c oxidase-negative, which exhibited higher levels of mitochondrial DNA deletions than cytochrome c oxidase-positive cells (60.38±3.92% versus 45.18±2.83%). Survival of dopaminergic neurons in POLGD257A mice was associated with increased mitochondrial DNA copy number, enhanced mitochondrial cristae network, improved mitochondrial respiration, decreased exacerbation of mitochondria-derived reactive oxygen species, greater striatal dopamine levels and resistance to parkinsonian mitochondrial neurotoxins. These results indicate that primary accumulation of mitochondrial DNA deletions within substantia nigra pars compacta dopaminergic neurons, at an extent similar to that observed in patients with Parkinson's disease, do not kill dopaminergic neurons but trigger neuroprotective compensatory mechanisms at a mitochondrial level that may account for the high pathogenic threshold of mitochondrial DNA deletions in these cells.
10.1093/brain/awt196
pubmed_499_1081
Exposure to childhood maltreatment (CM) increases the risk of developing borderline personality disorder (BPD). However, it remains unclear what mechanisms might mediate this link. One candidate of interest is difficulties with emotion regulation. This study aims to examine the pattern of relations among CM, difficulties with emotion regulation, and the risk of developing BPD. A total of 162 individuals diagnosed with current BPD and 162 matched healthy controls completed self-reported questionnaires assessing CM and difficulties with emotion regulation. The authors found high correlations between CM and BPD diagnosis (r = .73, p < .001). Difficulties with emotion regulation were found to mediate the link between CM and BPD diagnosis (p < .001). Results suggest that CM may play a key role in the etiology of BPD and that difficulties with emotion regulation might be a mediating component between CM and BPD.
10.1521/pedi.2022.36.3.264
pubmed_1015_10804
Fifteen permanent cell lines derived from human gliomas which are individually distinct by immunologic and biochemical criteria were evaluated to determine if morphologic or cell biologic parameters distinguished the 4 lines which were tumorigenic in athymic nude mice. By subjective morphologic appraisal, the 4 tumorigenic lines were considered "malignant" or "borderline," but 4 of the non-tumorigenic lines were also classified in this way. By objective criteria, these 15 lines varied markedly in percentage of piled-up cells, chromatin pattern, pleomorphism, nuclear to cytoplasmic ratio, number of bizarre multinucleate giant cells, presence of abnormal mitotic figures, percentage of colony formation in soft agar, saturation density, population doubling time, and absolute plating efficiency. Among these criteria, percentage of colony formation in soft agar had the highest correlation coefficiency with tumorigenicity, and when this parameter was held constant the only additional characteristic which correlated significantly (p less than .05) was the number of bizarre multinucleate giant cells. When the 11 non-tumorigenic lines were ranked by these 2 criteria, 1 non-tumorigenic line (U-251 MGsp) had greater than .95 predicted probability of tumorigenicity. Although further tumorigenicity testing may increase the number of tumorigenic lines, the lines with few "malignant" characteristics may correspond to the population resembling cells of low grade astrocytomas seen within glioblastomas. The histologic pleomorphism of human gliomas is reflected in their morphologic and cell biologic diversity in culture.
10.1097/00005072-198107000-00004
pubmed_150_15042
Zero-profile device was applied to diminish the irritation of the esophagus in the treatment of cervical degenerative disc disease. However, the clinical application of the zero-profile device has not been testified with clinical evidence. The aim of the meta-analysis was to systematically compare the safety and effectiveness of anterior cervical discectomy and fusion with zero-profile device with plate and cage for the treatment of cervical degenerative disc disease. Electronic searches of PubMed and Embase were conducted up to May 2015. Relevant studies were included. Weighted mean difference (WMD) and 95% confidence intervals (CI) were assessed for continuous data. Risk ratio (RR) and 95% CI were assessed for dichotomous data. P value <0.05 was considered to be significant. Eleven studies were included in the meta-analysis. Compared with plate and cage, zero-p is associated with lower operation time of two-level surgery, less intraoperative blood loss, higher subsidence rate, higher JOA score, lower incidence of dysphagia in short-term (RR: 0.72, 95% CI [0.58, 0.90], P=0.005, I2=22%) and long-term (RR: 0.12, 95% CI [0.05, 0.30], P<0.00001, I2=0%) and lower Cobb angle of multilevel surgery (WMD: -3.16, 95% CI: [-4.35, -1.97], P<0.00001, I2=0%). No significant difference was found in one-level and two-level Cobb angle, fusion rate and operation time of one-level and three-level surgery. Both zero-p implantation and the plate and cage have respective advantages and disadvantages.
10.1016/j.jocn.2016.01.046
pubmed_315_12461
Recent studies have shown that elongation factors extracted from archaea/eukarya and from eubacteria exhibit different structural and functional properties. Along this line, it has been demonstrated that, in contrast to EF-Tu, Sulfolobus solfataricus EF-1alpha in complex with GDP (SsEF-1alpha.GDP) does not bind Mg(2+), when the ion is present in the crystallization medium at moderate concentration (5 mM). To further investigate the role that magnesium plays in the exchange process of EF-1alpha and to check the ability of SsEF-1alpha.GDP to bind the ion, we have determined the crystal structure of SsEF-1alpha.GDP in the presence of a nonphysiological concentration (100 mM) of Mg(2+). The analysis of the coordination of Mg(2+) unveils the structural bases for the marginal role played by the ion in the nucleotide exchange process. Furthermore, nucleotide exchange experiments carried out on a truncated form of SsEF-1alpha, consisting only of the nucleotide binding domain, demonstrate that the low affinity of SsEF-1alpha.GDP for Mg(2+) is due to the local architecture of the active site and does not depend on the presence of the other two domains. Finally, considering the available structures of EF-1alpha, a detailed mechanism for the nucleotide exchange process has been traced. Notably, this mechanism involves residues such as His14, Arg95, Gln131, and Glu134, which are strictly conserved in all archaea and eukarya EF-1alpha sequences hitherto reported.
10.1021/bi0363331
pubmed_1103_13835
Anti-Yo antibodies are present in the sera and cerebrospinal fluid of some patients with paraneoplastic cerebellar degeneration (PCD), but there is no evidence that the presence of anti-Yo antibodies causes the Purkinje cell loss seen in PCD patients. We examined the level of cytotoxic T lymphocyte (CTL) activity against a nine-amino acid peptide of the Yo protein using the Human Leukocyte Antigen- (HLA-) based approach called reverse immunogenetics. Mononuclear cells (MNCs) were isolated from the peripheral venous blood and fibroblasts were obtained from the skin of three patients with PCD with anti-Yo antibody. After activating the MNCs of the three patients with the peptide, it showed CTL activity against the Yo protein peptide expressed on autologous fibroblasts. Therefore, CTLs may be involved in the loss of Purkinje cells in PCD.
10.1016/s0022-510x(99)00163-x
pubmed_509_15748
OBJECTIVE Inverted papilloma is associated with sinonasal squamous cell carcinoma. This study aimed to investigate the epigenetic regulation of the tumour suppressor gene DLEC1 in inverted papilloma and sinonasal squamous cell carcinoma. METHODS DLEC1 gene expression was investigated by quantitative real-time polymerase chain reaction (QRT-PCR) in normal mucosa, inverted papilloma, and squamous cell carcinoma tissues. Methylation-specific PCR and subsequent autosequencing were also used to examine the methylation status of DLEC1 promoter and the involved mechanism. DLEC1 expression in a large validation set was evaluated by immunohistochemistry (n  =  25 in each group). RESULTS DLEC1 was downregulated in inverted papilloma and squamous cell carcinoma tissues compared to normal mucosa (p < .01 in QRT-PCR and immunohistochemistry), with squamous cell carcinoma more repressed (p < .05 in QRT-PCR and immunohistochemistry) than inverted papilloma tissues. DLEC1 promoter hypermethylation was found in squamous cell carcinoma tissues. CONCLUSION Repression of DLEC1 in squamous cell carcinoma tissues is associated with promoter hypermethylation. DLEC1 is downregulated in sinonasal squamous cell carcinoma and inverted papilloma and has a distinct mechanism.
pubmed_509_15748
pubmed_308_11471
A field infrared temperature-increasing simulation experiment was conducted to investi- gate the effects of air temperature increases (0, 1 and 2 °C ) on growth, development and yield of spring wheat at the Dingxi Arid Meteorology and Ecological Environment Experimental Station of the Institute of Arid Meteorology of China Meteorological Administration. The results showed that the growth period of spring wheat was shortened by 7-11 d when the temperature increased by 1-2 °C. The plant height and leaf area index increased at early growth stage, decreased after entering the jointing stage, and warming 2 °C had a higher effect than warming 1 °C. Warming treatment induced an obvious decrease in chlorophyll content, especially from late grain filling stage to milk ripe stage. Compared with the control, increasing temperature by 1-2 °C decreased the spring wheat yield by 25.4%-45.5%, mainly due to obvious decreases in number of grains and grain mass per panicle. Water consumption of 0-100 cm soil horizons increased with the increase of temperature, while the variation tendency of water consumption of 100-160 cm soil horizons was not obvious.
pubmed_308_11471
pubmed_1003_19781
The study utilizes an oral biocompatible material based on ethylene vinyl acetate copolymer (EVA) designed to release drugs in vitro at therapeutic levels over several days. We examined the drug stability during film casting process using proton and solid state NMR techniques. The drug-loaded EVA films were prepared from the dry sheet obtained by solvent (dichloromethane) evaporation of polymer casting solutions. Drugs tested include chlorhexidine diacetate (CDA), doxycycline hydrochloride (DOH), tetracycline hydrochloride (TTH) and nystatin (NST). Drug release from the films was examined for at least 14 days in 10 ml ddH2O (NST in water/ethanol (4:1)) which was replaced daily. Changes in optical density were followed spectraphotometrically. Effect of temperature on rate measurements was studied and the energies of activation (E*) were calculated using Arrhenius plots. Effect of EVA copolymer composition on CDA release rate was also investigated. The enhanced rates with temperature increase may be attributed to the formation of channels with increased geometry in the polymer. The highest E* observed for CDA compared to DOH and TTH may be related to their average molecular weights. Spectral analyses for CDA and NST revealed that the chemical and physical structures of the drugs remained unaffected during the film casting process.
10.1007/s10856-005-2529-1
pubmed_236_3338
During a two-year period, January 1989 to January 1991, 39 (12%) of 331 children admitted to various hospitals and health centres in Enugu and Nsukka areas of Eastern Nigeria with symptoms of meningitis had Haemophilus influenzae isolated from their cerebrospinal fluids (CSF). 90% were aged 24 months and below. Out of the 39 isolates, 37 were Pittman serotype b while the remaining 2 were type d. More males (61.5%) had H. influenzae meningitis in comparison with 38.5% of females. 69.2% of the cases occurred during the dry season while 30.7% occurred during the rainy season. All the isolates were sensitive to chloramphenicol and erythromycin, while 90% were sensitive to ampicillin and penicillin, using the disc diffusion method. The leading role of H. influenzae in meningitis in children who are 7 to 24 months of age in this part of the world and the increasing resistance of this organism to ampicillin and penicillin is hereby stressed.
pubmed_236_3338
pubmed_565_1445
Serial study using MR imaging and 1H-MR spectroscopy (1H-MRS) of unidentified bright objects (UBO) in a 9-year-old boy with neurofibromatosis type 1 (NF1) is described. UBO was indicated in the left globus pallidum at 3 years old, then appeared in the right globus pallidum at 5 years old along with left hemiconvulsion. These UBO gradually disappeared over several years. On 1H-MRS, the ratios of N-acetylaspartate (NAA)/creatine and that of choline/creatine were each mildly reduced in the UBO. These ratios improved in parallel with disappearance of the UBO. In addition, elevation of the lactate/lipid peak was shown in UBO during the early stage, however, it disappeared in the latter. The longitudinal follow-up using MR image and 1H-MRS was useful for metabolic evaluation of UBO in patients with NF1.
10.1016/j.braindev.2005.02.008
pubmed_81_15794
OBJECTIVE To present a simple, fast, and efficient technique to control bleeding from the epidural venous plexus during anterior cervical discectomy. METHODS When encountering persistent bleeding from the venous epidural plexus during anterior cervical discectomy that cannot be controlled by bipolar coagulation, one can take approximately 5 to 10 ml of saline and connect the syringe to a curved blunt cannula with an atraumatic tip. Subsequently, the atraumatic tip of the syringe is placed between the dura and the bony edge and then the saline is powerfully injected into the epidural space. This will stop the bleeding. RESULTS This technique has been applied in 118 cases of anterior cervical discectomies and has proven to be very effective. We did not have to apply another hemostatic technique to control bleeding from the epidural plexus in any of our cases. CONCLUSION We present a simple and effective hemostasis technique to control bleeding from the cervical epidural venous plexus by injecting saline into the epidural space. We speculate that the mechanism by which the bleeding is controlled consists of filling the epidural space with saline; this elevated "pressure" controls the bleeding in a very effective way. Moreover, some venous contraction may occur because of the saline injection.
10.1227/01.neu.0000326032.31843.42
pubmed_938_14377
In an effort to preserve Mycobacterium leprae in vitro, the effect of freezing and drying, i.e., lyophilization, on viability of M. leprae was studied. The viability of the bacilli was quantitatively measured with foot-pad inoculation method using nude mouse. The results obtained demonstrate that the viability of M. leprae was reduced approximately 10(-2) to 10(-3) from that of the starting material, during the process of lyophilization; no viable bacilli were detected in the lyophilized sample containing less than 1.8 X 10(3) bacilli. On the other hand, the bacilli capable of multiplication in nude mouse foot-pads were found in the lyophilized sample with more than 10(5) bacilli. From the results obtained here, it could be suggested that there might be a possibility to preserve M. leprae in vitro by means of lyophilization.
pubmed_938_14377
pubmed_795_20210
Tobacco-associated carcinogens are catalyzed by microsomal epoxide hydrolase (mEH). Combinations of the Y113H and H139R polymorphic EPHX1 variants have been assumed to alter the enzyme activity and thus the risk of squamous cell head and neck cancer (SCCHN). Based on in vitro data, a putative low, medium and high mEH activity has been associated with combinations of these genotypes, and the respective activity categories have been frequently used in the estimation of risks for smoking-related cancers. We investigated the SCCHN risk for EPHX1 genotypes among 280 cases and 289 controls. We could not detect main effects of the EPHX1 genotypes, but a smaller risk of the 139HR genotype in smokers (odds ratio, OR, 0.57; 95% confidence interval, CI, 0.34-0.95). We could not confirm an increase of the SCCHN risk for genotype combinations according to a putative medium and high enzyme activity (OR 1.28, 95% CI 0.84-1.96; OR 0.98, 95% CI 0.58-1.64, respectively), but a significant heterogeneity of the estimated risks for the singular genotypes within these categories among smokers ( P=0.02). Further, p53 mutations among smoking cases were less frequent in the group with a putative high enzyme activity, although insignificant due to small numbers (OR 0.54, 95% CI 0.13-2.17). This supports uncertainties in categorizing genotypes with respect to limited enzyme activity data, especially when taken from in vitro experiments.
10.1007/s00204-002-0414-y
pubmed_1059_6801
The problems in the pathophysiology of chronic recurrent mastitis in association with galactorrhea are discussed. The discussion was centered around the role of Prolactin. Treatment consists of inhibition of Prolactin by Bromocryptin following exclusion of other conditions of importance in the differential diagnosis.
pubmed_1059_6801
pubmed_1105_20977
A rapid, simple, and sensitive differential kinetic method is presented for the determinations of acetaminophen (also known as paracetamol) and salicylamide. The method is based on their oxidation reaction by Fe3+ ion in the presence of 1, 10-phenanthroline as indicator. The reactions can be monitored spectrophotometrically by measuring the increase in the absorbance of the solution at 510 nm. Two times were selected one in which only paracetamol is oxidized by Fe3+ ion and the other in which both drugs are oxidized by Fe3+ ion. The data were evaluated by the proportional equations method. The method allowed the simultaneous determination of paracetamol and salicylamide at concentrations between 0.5-20 and 1-40 microg/mL with relative standard deviations of 3.47 and 2.58%, respectively. The method was applied to the simultaneous determination of paracetamol and salicylamide in human serum and pharmaceutical formulations.
pubmed_1105_20977
pubmed_490_8548
The bipartite genome of an Indian isolate of Bombyx mori bidensovirus (BmBDV), one of the causative agents of the fatal silkworm disease 'Flacherie', was cloned and completely sequenced. Nucleotide sequence analysis of this Indian isolate of BmBDV revealed two viral DNA segments, VD1 and VD2 as well as a DNA polymerase motif which supports its taxonomical status as the type species of a new family of Bidnaviridae. The Indian isolate of BmBDV was found to have a total of six putative ORFs four of which were located on the VD1 with the other two being on the VD2 DNA segment. The VD1 DNA segment was found to code for three non-structural proteins including a viral DNA polymerase as well as one structural protein, while the VD2 DNA segment was found to code for one structural and one non-structural protein, similar to that of the Japanese and Zhenjiang isolates of BmBDV. A BmBDV ORF expression study was done through real time qPCR wherein the VD2 ORF 1 and 2 showed the maximum transcript levels. This is the first report of the genome characterization of an Indian isolate of BmBDV, infecting silkworm B. mori.
10.1007/s00705-017-3584-x
pubmed_617_18522
L-2-Hydroxyglutaric aciduria (L2HGA) is a rare, neurometabolic disorder with an autosomal recessive mode of inheritance. Affected individuals only have neurological manifestations, including psychomotor retardation, cerebellar ataxia, and more variably macrocephaly, or epilepsy. The diagnosis of L2HGA can be made based on magnetic resonance imaging (MRI), biochemical analysis, and mutational analysis of L2HGDH. About 200 patients with elevated concentrations of 2-hydroxyglutarate (2HG) in the urine were referred for chiral determination of 2HG and L2HGDH mutational analysis. All patients with increased L2HG (n=106; 83 families) were included. Clinical information on 61 patients was obtained via questionnaires. In 82 families the mutations were detected by direct sequence analysis and/or multiplex ligation dependent probe amplification (MLPA), including one case where MLPA was essential to detect the second allele. In another case RT-PCR followed by deep intronic sequencing was needed to detect the mutation. Thirty-five novel mutations as well as 35 reported mutations and 14 nondisease-related variants are reviewed and included in a novel Leiden Open source Variation Database (LOVD) for L2HGDH variants (http://www.LOVD.nl/L2HGDH). Every user can access the database and submit variants/patients. Furthermore, we report on the phenotype, including neurological manifestations and urinary levels of L2HG, and we evaluate the phenotype-genotype relationship.
10.1002/humu.21197
pubmed_551_24516
BACKGROUND Chronic myeloid leukemia (CML) is a myeloproliferative disorder of blood stem cells. The tyrosine kinase inhibitor (TKI) imatinib was the first targeted therapy licensed for patients with chronic-phase CML, and its introduction was associated with substantial improvements in response and survival compared with previous therapies. Clinical trial data are now available for the second-generation TKIs (nilotinib, dasatinib, and bosutinib) in the first-, second-, and third-line settings. A qualitative systematic review was conducted to qualitatively compare the clinical effectiveness, safety, and effect on quality of life of TKIs for the management of chronic-, accelerated-, or blast-phase CML patients. METHODS Included studies were identified through a search of electronic databases in September 2011, relevant conference proceedings and the grey literature. RESULTS In the first-line setting, the long-term efficacy (up to 8 years) of imatinib has been confirmed in a single randomized controlled trial (International Randomized Study of Interferon [IRIS]). All second-generation TKIs reported lower rates of transformation, and comparable or superior complete cytogenetic response (CCyR), major molecular response (MMR), and complete molecular response rates compared with imatinib by 2-year follow-up. Each of the second-generation TKIs was associated with a distinct adverse-event profile. Bosutinib was the only second-generation TKI to report quality-of-life data (no significant difference compared with imatinib treatment). Data in the second- and third-line setting confirmed the efficacy of the second-generation TKIs in either imatinib-resistant or -intolerant patients, as measured by CCyR and MMR rates. CONCLUSION Data from first-line randomized controlled trials reporting up to 2-year follow-up indicate superior response rates of the second-generation TKIs compared with imatinib. Current evidence from single-arm studies in the second-line setting confirm that nilotinib, dasatinib, and bosutinib are valuable treatment options for the significant subgroup of patients who are intolerant or resistant to imatinib treatment.
10.2147/JBM.S33380
pubmed_39_8520
After withdrawal from cocaine, chronic cocaine users often experience persistent reduction in total sleep time, which is accompanied by increased sleep fragmentation resembling chronic insomnia. This and other sleep abnormalities have long been speculated to foster relapse and further drug addiction, but direct evidence is lacking. Here, we report that after prolonged withdrawal from cocaine self-administration, rats exhibited persistent reduction in nonrapid-eye-movement (NREM) and rapid-eye-movement (REM) sleep, as well as increased sleep fragmentation. In an attempt to improve sleep after cocaine withdrawal, we applied chronic sleep restriction to the rats during their active (dark) phase of the day, which selectively decreased the fragmentation of REM sleep during their inactive (light) phase without changing NREM or the total amount of daily sleep. Animals with improved REM sleep exhibited decreased incubation of cocaine craving, a phenomenon depicting the progressive intensification of cocaine seeking after withdrawal. In contrast, experimentally increasing sleep fragmentation after cocaine self-administration expedited the development of incubation of cocaine craving. Incubation of cocaine craving is partially mediated by progressive accumulation of calcium-permeable AMPA receptors (CP-AMPARs) in the nucleus accumbens (NAc). After withdrawal from cocaine, animals with improved REM sleep exhibited reduced accumulation of CP-AMPARs in the NAc, whereas increasing sleep fragmentation accelerated NAc CP-AMPAR accumulation. These results reveal a potential molecular substrate that can be engaged by sleep to regulate cocaine craving and relapse, and demonstrate sleep-based therapeutic opportunities for cocaine addiction. Significance statement: Sleep abnormalities are common symptoms in chronic drug users long after drug withdrawal. These withdrawal-associated sleep symptoms, particularly reduction in total sleep time and deteriorating sleep quality, have been speculated to foster relapse and further drug addiction, but direct evidence is lacking. Here we show in rats that the sleep pattern was persistently changed long after withdrawal from cocaine self-administration, and demonstrate that sleep interventions can bidirectionally regulate cocaine craving and seeking after withdrawal. We further demonstrate that glutamatergic synapses in the nucleus accumbens are potential neuronal targets for sleep intervention to influence cocaine craving after withdrawal. These results provide a strong rationale supporting sleep-based therapies for cocaine addiction.
10.1523/JNEUROSCI.1065-15.2015
pubmed_446_13218
We study coherent perfect absorption (CPA) of light in a Kerr nonlinear metal-dielectric composite medium, illuminated from the opposite ends. Elementary symmetry considerations reveal that equality of the incident light intensities is a prerequisite to ensure CPA in both linear and nonlinear systems for specific system parameters. We also derive the sufficient conditions for having CPA. We further show that, while CPA in a linear system is insensitive to the incident power level, in a nonlinear system CPA can be achieved only for discrete intensities with interesting hysteretic responses. Our unified formulation of CPA and waveguiding identifies them as opposite scattering phenomena. We further investigate light-induced CPA in on-resonant and off-resonant systems.
10.1364/OL.38.005252
pubmed_1051_6667
Globally, stroke is a leading cause of death and long-term disability. Over the past decades, several efforts have attempted to discover new drugs or repurpose existing therapeutics to promote post-stroke neurological recovery. Preclinical stroke studies have reported successes in identifying novel neuroprotective agents; however, none of these compounds have advanced beyond a phase III clinical trial. One reason for these failures is the lack of consideration of blood-brain barrier (BBB) transport mechanisms that can enable these drugs to achieve efficacious concentrations in ischemic brain tissue. Despite the knowledge that drugs with neuroprotective properties (i.e., statins, memantine, metformin) are substrates for endogenous BBB transporters, preclinical stroke research has not extensively studied the role of transporters in central nervous system (CNS) drug delivery. Here, we review current knowledge on specific BBB uptake transporters (i.e., organic anion transporting polypeptides (OATPs in humans; Oatps in rodents); organic cation transporters (OCTs in humans; Octs in rodents) that can be targeted for improved neuroprotective drug delivery. Additionally, we provide state-of-the-art perspectives on how transporter pharmacology can be integrated into preclinical stroke research. Specifically, we discuss the utility of in vivo stroke models to transporter studies and considerations (i.e., species selection, co-morbid conditions) that will optimize the translational success of stroke pharmacotherapeutic experiments.
10.3390/ijms23031898
pubmed_719_3091
BACKGROUND AND OBJECTIVES The association between plant-based diets, incident CKD, and kidney function decline has not been examined in the general population. We prospectively investigated this relationship in a population-based study, and evaluated if risk varied by different types of plant-based diets. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Analyses were conducted in a sample of 14,686 middle-aged adults enrolled in the Atherosclerosis Risk in Communities study. Diets were characterized using four plant-based diet indices. In the overall plant-based diet index, all plant foods were positively scored; in the healthy plant-based diet index, only healthful plant foods were positively scored; in the provegetarian diet, selected plant foods were positively scored. In the less healthy plant-based diet index, only less healthful plant foods were positively scored. All indices negatively scored animal foods. We used Cox proportional hazards models to study the association with incident CKD and linear mixed models to examine decline in eGFR, adjusting for confounders. RESULTS During a median follow-up of 24 years, 4343 incident CKD cases occurred. Higher adherence to a healthy plant-based diet (HR comparing quintile 5 versus quintile 1 [HRQ5 versus Q1], 0.86; 95% confidence interval [95% CI], 0.78 to 0.96; P for trend =0.001) and a provegetarian diet (HRQ5 versus Q1, 0.90; 95% CI, 0.82 to 0.99; P for trend =0.03) were associated with a lower risk of CKD, whereas higher adherence to a less healthy plant-based diet (HRQ5 versus Q1, 1.11; 95% CI, 1.01 to 1.21; P for trend =0.04) was associated with an elevated risk. Higher adherence to an overall plant-based diet and a healthy plant-based diet was associated with slower eGFR decline. The proportion of CKD attributable to lower adherence to healthy plant-based diets was 4.1% (95% CI, 0.6% to 8.3%). CONCLUSIONS Higher adherence to healthy plant-based diets and a vegetarian diet was associated with favorable kidney disease outcomes.
10.2215/CJN.12391018
pubmed_370_4688
A comparison is made of the data drawn from Hospital statistics for the period 1965-79 with regard to antibiograms from patients with first T. B. observations. A progressive reduction in primary resistance in the general sense was noted, with an increase in the case of RAMP only. There was a constant decrease for INH, PAS and ETB, whereas SM, KM and CS values were stationary. The conclusion is drawn that the reduction in primary resistance notwithstanding the continual employment of these drugs must be attributed to the fact that the resistant mycobacteria have depressed proliferative capacity and virulence. Primary resistance, therefore, while a good pointer to the epidemiology of T.B. infection, is not a cause for concern from the therapeutic standpoint.
pubmed_370_4688
pubmed_564_14160
A biocultural study of the side effects of chronic lithium treatment among 70 Hong Kong Chinese psychiatric patients, using a self-report 33-item checklist and semi-structured interviews, revealed an imperfect correspondence between biomedically prescribed and culturally endorsed psychotropic side effects. Although polydipsia and polyuria (47%) were the biomedically most 'real' side effects, they were not usually regarded as bothersome or translated into metaphors to express undesirable side effects. Complaints such as tiredness (38%), drowsiness (36%) and poor memory (31%) were also common but their frequency was significantly lower than that of normal control subjects. The item 'loss of creativity' had no conceptual equivalent in Chinese and was usually misinterpreted. As no patient was aware that lithium was a metal, the side effect 'metallic taste' was variously labelled. Contrary to Western findings, complaints of 'missing of highs', loss of assertiveness and fear of weight gain were rarely encountered. Active elicitation was required for indigenous complaints, with 38% of patients considering lithium to cause mild "hotness." This was readily neutralized by drinking more water which had a "cooling" effect. Expectedly, concurrent neuroleptics and antidepressants amplified most lithium side effects. This study affirms Western data on the biomedically universalizable effects of chronic lithium treatment, but also supports the thesis that culturally constituted cognitive styles affect patients' recognition, labelling, experiencing and reporting the total drug effect. Further, it demonstrates that the lived experience and clinical negotiation of lithium associated side effects reproduce, authenticate, and at times critique, core cultural and moral premises of Western and Chinese societies.
10.1007/BF01380006
pubmed_920_10139
Background: In the Netherlands, a digital decision support system for telephone triage at out-of-hours services in primary care (OHS-PC) is used. Differences in help-seeking behavior between men and women when transient ischemic attack (TIA) or stroke is suspected could potentially affect telephone triage and allocation of urgency. Aim: To assess patient and call characteristics and allocated urgencies between women and men who contacted OHS-PC with suspected TIA/stroke. Methods: A cross-sectional study of 1,266 telephone triage recordings of subjects with suspected neurological symptoms calling the OHS-PC between 2014 and 2016. The allocated urgencies were derived from the electronic medical records of the OHS-PC and the final diagnosis from the patient's own general practitioner, including diagnoses based on hospital specialist letters. Results: Five hundred forty-six men (mean age = 67.3 ± 17.1) and 720 women (mean age = 69.6 ± 19.5) were included. TIA/stroke was diagnosed in 294 men (54%) (mean age = 72.3 ± 13.6) and 366 women (51%) (mean age = 78.0 ± 13.8). In both genders, FAST (face-arm-speech test) symptoms were common in TIA/stroke (men 78%, women 82%) but also in no TIA/stroke (men 63%, women 62%). Men with TIA/stroke had shorter call durations than men without TIA/stroke (7.10 vs. 8.20 min, p = 0.001), whereas in women this difference was smaller and not significant (7.41 vs. 7.56 min, p = 0.41). Both genders were allocated high urgency in 75% of the final TIA/stroke cases. Conclusion: Overall, patient and call characteristics are mostly comparable between men and women, and these only modestly assist in identifying TIA/stroke. There were no gender differences in allocated urgencies after telephone triage in patients with TIA/stroke.
10.3389/fneur.2021.669090