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pubmed_989_13260 | Background
Osteoarthritis (OA) is a major cause of chronic pain and lameness in dogs. Platelet-rich plasma (PRP) is a concentrate of growth and differentiation factors from the blood, which can be used in regenerative medicine strategies.
Aim
The main aim of this study was to evaluate the effect of allogeneic PRP on the treatment of canine OA.
Methods
Five dogs from several breeds, between 6 and 12 years old, and from both genders were studied. Clinical and imageological examinations diagnosed OA in the knee, tibiotarsal, elbow, and intercarpal joints. These dogs were refractory to medical therapy and to physical rehabilitation protocols that included shockwave therapy, laser therapy, electrostimulation, hydrotherapy, and diathermy.Animals were treated with allogeneic PRP obtained from the blood of the five dogs, which was processed in a pool. Echoguided intra-articular PRP injection was administered under sedation and after aseptic field preparation. Lameness at walk and trot (five grades) and pain (five scores) were evaluated before treatment and 30, 60, and 90 days post-treatment.
Results
All animals presented improvements at 30 and 60 days in both parameters. Four dogs showed a decrease of three grades of lameness after 90 days and there was complete absence of lameness in 2 days. Pain was reduced from severe and moderate to mild in all the dogs after 30 days, and among them, three revealed no pain after 90 days.
Conclusion
This study sheds light on the applicability and safety of a single administration of allogeneic PRP in osteoarthritic dogs. | 10.4314/ovj.v10i2.12 |
pubmed_505_11337 | The stromal cell-derived factor-1 (SDF-1)/CXCR4 system is implicated in various instances of cell migration in mammals, including the migration of lymphocytes and the formation of metastases. We have recently synthesized a potent novel CXCR4 antagonist, TN14003. The purpose of this study was to investigate the role of SDF-1/CXCR4 axis in the pancreatic cancer metastasis via cell migration and invasion, and the inhibitory effect of TN14003 on pancreatic cancer cell metastasis. The expression of CXCR4 was detected in six pancreatic cancer cell lines by Western blotting and immunocytochemistry. In migration and invasion assays, SDF-1 stimulated both migration and invasion of cancer cells in a dose-dependent manner. The maximal effect of SDF-1 was observed at 100 ng/ml. SDF-1-induced migration and invasion of cancer cells were completely blocked by 100 nM TN14003. The stimulatory effect of SDF-1 on cancer migration and the inhibitory effect of TN14003 were mediated via the alteration in phosphorylation of mitogen-activated protein kinases. Treatment of cancer cells with 100 ng/ml SDF-1 resulted in a significant increase of actin polymerization, which was reduced by 100 nM TN14003. SDF-1 enhanced cancer cell adhesion to laminin, which was not reversed by TN14003. Taken together, SDF-1/CXCR4 axis is involved in pancreatic cancer metastasis through migration and invasion. The small molecule antagonists against CXCR4 such as TN14003 might be an effective anti-metastatic agent for pancreatic cancer. | pubmed_505_11337 |
pubmed_123_18957 | The cell inhibition activities of several Annonaceous acetogenins, covering the three major structural classes of bis-adjacent, bis-non-adjacent, and single tetrahydrofuran (THF) ring compounds and their respective ketolactone rearrangement products, were tested in an in vitro disk diffusion assay against three murine (P388, PO3, and M17/Adr) and two human (H8 and H125) cancerous cell lines as well as a non-cancerous immortalized rat GI epithelial cell line (I18). The results demonstrate a dose-dependent inhibition of cancerous cell growth, while non-cancerous cell growth is not inhibited by the same dosages. All of the acetogenins, irrespective of their various structural types, inhibit the growth of adriamycin resistant tumor cells and non-resistant tumor cells at the same levels of potency. These results show that the Annonaceous acetogenins are an extremely potent class of compounds, and their inhibition of cell growth can be selective for cancerous cells and also effective for drug resistant cancer cells, while exhibiting only minimal toxicity to 'normal' non-cancerous cells. | 10.1016/0304-3835(95)92759-7 |
pubmed_835_5595 | The literature has few studies on the seasonality of tuberculosis (TB) in the southern hemisphere, entailing the fill of this knowledge gap. This study aims to analyze whether TB incidence in Brazilian capitals and the Federal District is seasonal. This is an ecological study of a time series (2001-2019) of TB cases, conducted with 26 capitals and the Federal District. The Ministry of Health database, with 516,524 TB cases, was used. Capitals and the Federal District were divided into five groups based on social indicators, disease burden, and the Koppen climate classification. The seasonal variation of TB notifications and group amplitude were evaluated. We found TB seasonality in Brazil with a 1% significance in all capital groups (Stability assumption and Krusall-Wallis tests, p < 0.01). In the combined seasonality test, capital groups A, D, and E showed seasonality, whereas groups B and C, its probability. Our findings showed that health service supply and/or demand - rather than climate - may be the most relevant underlying factor in TB seasonality. It is challenging to raise the other seasonal factors underlying TB seasonality in tropical regions in the Southern Hemisphere. | 10.1590/0102-311XPT291321 |
pubmed_433_7429 | Congenital scoliosis (CS) is a form of scoliosis caused by congenital vertebral malformations. Genetic predisposition has been demonstrated in CS. We previously reported that TBX6 loss-of-function causes CS in a compound heterozygous model; however, this model can explain only 10% of CS. Many monogenic and polygenic CS genes remain to be elucidated. In this study, we analyzed exome sequencing (ES) data of 615 Chinese CS from the Deciphering Disorders Involving Scoliosis and COmorbidities (DISCO) project. Cosegregation studies for 103 familial CS identified a novel heterozygous nonsense variant, c.2649G>A (p.Trp883Ter) in FBN1. The association between FBN1 and CS was then analyzed by extracting FBN1 variants from ES data of 574 sporadic CS and 828 controls; 30 novel variants were identified and prioritized for further analyses. A mutational burden test showed that the deleterious FBN1 variants were significantly enriched in CS subjects (OR = 3.9, P = 0.03 by Fisher's exact test). One missense variant, c.2613A>C (p.Leu871Phe) was recurrent in two unrelated CS subjects, and in vitro functional experiments for the variant suggest that FBN1 may contribute to CS by upregulating the transforming growth factor beta (TGF-β) signaling. Our study expanded the phenotypic spectrum of FBN1, and provided nove insights into the genetic etiology of CS. | 10.1038/s10038-019-0698-x |
pubmed_1064_5733 | OBJECT
Glial cell line-derived neurotrophic factor (GDNF) has been shown to confer neuroprotective effects on dopaminergic neurons. The authors investigated the effects of GDNF on 6-hydroxydopamine (6-OHDA)-treated dopaminergic neurons in vitro and in vivo.
METHODS
First, the authors examined how 1, 10, or 100 ng/ml of GDNF, administered to cells 24 hours before, simultaneously with, or 2 or 4 hours after 6-OHDA was added, affected dopaminergic neurons. In a primary culture of E14 murine ventral mesencephalic neurons, earlier treatment with the higher dosage of GDNF suppressed 6-OHDA-induced loss of dopaminergic neurons better than later treatment. Next, the authors examined whether continuous infusion of GDNF at earlier time points would demonstrate a greater neuroprotective effect in a rat model of Parkinson disease (PD). They established a human GDNF-secreting cell line, called BHK-GDNF, and encapsulated the cells into hollow fibers. The encapsulated cells were unilaterally implanted into the striatum of adult rats 1 week before; simultaneously with; or 1, 2, or 4 weeks after 6-OHDA was given to induce lesions of the same striatum. With the earlier transplantation of a BHK-GDNF capsule, there was a significant reduction in the number of amphetamine-induced rotations displayed by the animals. Rats that had received earlier implantation of BHK-GDNF capsules displayed more tyrosine hydroxylase-positive neurons in the substantia nigra pars compacta and a tendency for glial proliferation in the striatum.
CONCLUSIONS
These neuroprotective effects may be related to glial proliferation and signaling via the GDNF receptor alpha1. The results of this study support a role for this grafting technique in the treatment of PD. | 10.3171/jns.2005.102.1.0080 |
pubmed_448_412 | BACKGROUND
Due to the increasing demand for kidney transplants, sometimes donors with underlying medical conditions can be considered for living kidney donor transplant. Thalassemia is amongst the most common inherited disorders of hemoglobin globally, which is not restricted as an exclusion criterion. However, there is currently no study examine the safety and characteristics of kidney donors with thalassemia minor.
METHODS
All eligible live kidney donors between 2016 and 2019 with thalassemia minor at a tertiary hospital were recruited. Baseline characteristics, clinical and laboratory outcomes were investigated.
RESULTS
Fifteen donors (11 women, 55.5 ± 15.0 year-old) were included with a follow-up duration of 2 (1-4) years since operation. The most prevalent gene mutation among participants was DEL-SEA. No clinical manifestations of anemia were seen but 10 participants had mild anemia diagnosed from blood tests. Cardiovascular, liver and renal function were normal before nephrectomy. Until now, all donors are alive and maintain overall good health. Anemia condition is not affected, and the post-donation eGFR = 71.04 ± 11.54 mL/min/1.73m2 is comparable to outcomes of healthy donors reported in previous studies. Two donors are at risk of proteinuria at 1-year post-transplant with A/C ratio > 30 mg/g.
CONCLUSIONS
Thalassemia minor individuals who are non-transfusion-dependent, without anemia clinical manifestations and have no contraindications to kidney donation are safe to be donors in short-term. An eGFR of at least 80 mL/min/1.73m2 should be considered to avoid low post-donation eGFR, and awareness should be raised on thalassemia donors with even mild albuminuria. Nephrectomy does not worsen thalassemia. | 10.1186/s12882-021-02609-2 |
pubmed_890_10793 | It is recognised that those diagnosed with HIV infection over the age of 50 have higher rates of morbidity and mortality. Little is known about how clinical presentation at diagnosis of HIV varies within this group. We sought to compare clinical presentation and markers of outcome among those diagnosed with HIV aged 60 and over vs. those diagnosed aged 50-59, over a ten-year period. The results showed that 84/111 were diagnosed with HIV aged 50-59 and 27/111 aged ≥60. Ethnicity and HIV risk factors were similar between groups, and most infections were sexually acquired with 7.4% of those aged ≥60 suspected to have a recent infection. Median CD4 cell count at presentation was significantly lower in the ≥60 age group (111 vs. 249; p < 0.001), and the proportion with a CD4 cell count <50 was also significantly lower in this population (33% vs. 15%; p = 0.04). In keeping with this, the frequency of AIDS-defining illness at diagnosis was higher in the ≥60 group (38% vs. 4%; p < 0.001). Co-morbidities were found in both groups, and 38% of those aged ≥60 at diagnosis were known to have since died compared to 4% of those aged 50-59 at diagnosis ( p ≤ 0.01). Those aged ≥60 had lower CD4 cell counts at diagnosis and more AIDS-defining illnesses, highlighting the increased risk of poor outcomes in this group. The majority of infections were sexually acquired. More work is needed to understand survival in adults diagnosed with HIV at an older age and to consider those over 60 as a specific population worthy of further research. | 10.1177/0956462416685891 |
pubmed_299_18510 | The transcription factor Sip1 (Zeb2) plays multiple roles during CNS development from early acquisition of neural fate to cortical neurogenesis and gliogenesis. In humans, SIP1 (ZEB2) haploinsufficiency leads to Mowat-Wilson syndrome, a complex congenital anomaly including intellectual disability, epilepsy and Hirschsprung disease. Here we uncover the role of Sip1 in retinogenesis. Somatic deletion of Sip1 from mouse retinal progenitors primarily affects the generation of inner nuclear layer cell types, resulting in complete loss of horizontal cells and reduced numbers of amacrine and bipolar cells, while the number of Muller glia is increased. Molecular analysis places Sip1 downstream of the eye field transcription factor Pax6 and upstream of Ptf1a in the gene network required for generating the horizontal and amacrine lineages. Intriguingly, characterization of differentiation dynamics reveals that Sip1 has a role in promoting the timely differentiation of retinal interneurons, assuring generation of the proper number of the diverse neuronal and glial cell subtypes that constitute the functional retina in mammals. | 10.1242/dev.136101 |
pubmed_859_21666 | Determination of trace amounts of targets or even a single molecule target has always been a challenge in the detection field. Digital measurement methods established for single molecule counting of proteins, such as single molecule arrays (Simoa) or dropcast single molecule assays (dSimoa), are not suitable for detecting small molecule, because of the limited category of small molecule antibodies and the weak signal that can be captured. To address this issue, we have developed a strategy for single molecule detection of small molecules, called small molecule detection with single molecule assays (smSimoa). In this strategy, an aptamer is used as a recognition element, and an addressable DNA Nanoflower (DNF) attached on the magnetic beads surface, which exhibit fluorescence imaging, is employed as the output signal. Accompanied by digital imaging and automated counting analysis, E2 at the attomolar level can be measured. The smSimoa breaks the barrier of small molecule detection concentration and provides a basis for high throughput detection of multiple substances with fluorescence encoded magnetic beads. | 10.1021/acsami.2c15373 |
pubmed_869_3567 | The discovery of the cardioprotective properties of the Mediterranean diet is one of the great successes of epidemiology, and as a result elites around the globe now regularly consume Mediterranean products like olive oil. Although biochemical, clinical, and epidemiological studies have at least partly revealed how various components of this diet may protect the cardiovascular system, the reasons why this protection is conferred by a "Mediterranean" but not by many other European diets have not received so much attention. A plausible hypothesis is that, because of a combination of physico-geographical and socioeconomic circumstances, the variety of plant and animal food traditionally consumed by populations on the European shores of the Mediterranean Sea is relatively similar to that of the food available to the hunter-gatherers from whom we descend. Our organ systems have evolved to work optimally on such a diet, and have not had the chance to adapt to a diet containing, for example, more saturated fats and trans fatty acids, and less antioxidants and fiber. Understanding why the Mediterranean diet is cardioprotective is important for finding dietary solutions within the physico-geographical and socioeconomic constraints of the areas in which populations actually live, for example, by taking advantage of the cardioprotective properties of their traditional diets. This may in the longer run lead to a more sustainable approach to cardiovascular disease prevention. | 10.1016/j.jclinepi.2006.05.001 |
pubmed_294_2705 | In accordance with the Jewish view human life begins with the first breath. The consequences following are wide reaching for the bioethical arguing within prenatal medicine and abortion in particular. The Jewish understanding of the beginning of life is based on theological grounds (like the special emphasis on this life or the principle of "actuality before potentiality"). whose consequences are philosophically contestable. | pubmed_294_2705 |
pubmed_1037_4723 | Sulfur dioxide (SO2) is one of the most hazardous and common environmental pollutants. However, the development of room-temperature SO2 sensors is seriously lagging behind that of other toxic gas sensors due to their poor recovery properties. In this study, a light-assisted SO2 gas sensor based on polyaniline (PANI) and Ag nanoparticle-comodified tin dioxide nanostructures (Ag/PANI/SnO2) was developed and exhibited remarkable SO2 sensitivity and excellent recovery properties. The response of the Ag/PANI/SnO2 sensor (20.1) to 50 ppm SO2 under 365 nm ultraviolet (UV) light illumination at 20 °C was almost 10 times higher than that of the pure SnO2 sensor. Significantly, the UV-assisted Ag/PANI/SnO2 sensor had a rapid response time (110 s) and recovery time (100 s) to 50 ppm SO2, but in the absence of light, the sensors exhibited poor recovery performance or were even severely and irreversibly deactivated by SO2. The UV-assisted Ag/PANI/SnO2 sensor also exhibited excellent selectivity, superior reproducibility, and satisfactory long-term stability at room temperature. The increased charge carrier density, improved charge-transfer capability, and the higher active surface of the Ag/PANI/SnO2 sensor were revealed by electrochemical measurements and endowed with high SO2 sensitivity. Moreover, the light-induced formation of hot electrons in a high-energy state in Ag/PANI/SnO2 significantly facilitated the recovery of SO2 by the gas sensor. | 10.1021/acsami.1c14548 |
pubmed_517_1970 | This study compared the accessibility of the pros (advantages) and cons (disadvantages) of exercise in a group of non-exercisers and regular exercisers, using the Transtheoretical Model of behaviour change as a theoretical framework. Pre-contemplators (n = 18), and maintainers (n = 25), were asked to generate a list of 'advantages to taking part in exercise' (pro reasons), and a list of 'disadvantages to taking part in exercise' (con reasons). The time to generate their first item was recorded as well as the total number of items generated within 60 s. The results showed that pre-contemplators provided more con reasons relative to pro reasons; and maintainers provided more pro reasons relative to con reasons for exercise. Pre-contemplators were also quicker to provide their first con reason, relative to their first pro reason, but there was no difference in pro and con latencies in the maintainers. It was concluded that one reason pre-contemplation individuals do not participate in regular exercise may be because they cannot think of reasons to exercise. | 10.1080/13548500310001604540 |
pubmed_308_23090 | Accumulation of 2-methylcitric acid (2MCA) is observed in methylmalonic and propionic acidemias, which are clinically characterized by severe neurological symptoms. The exact pathogenetic mechanisms of brain abnormalities in these diseases are poorly established and very little has been reported on the role of 2MCA. In the present work we found that 2MCA markedly inhibited ADP-stimulated and uncoupled respiration in mitochondria supported by glutamate, with a less significant inhibition in pyruvate plus malate respiring mitochondria. However, no alterations occurred when α-ketoglutarate or succinate was used as respiratory substrates, suggesting a defect on glutamate oxidative metabolism. It was also observed that 2MCA decreased ATP formation in glutamate plus malate or pyruvate plus malate-supported mitochondria. Furthermore, 2MCA inhibited glutamate dehydrogenase activity at concentrations as low as 0.5 mM. Kinetic studies revealed that this inhibitory effect was competitive in relation to glutamate. In contrast, assays of osmotic swelling in non-respiring mitochondria suggested that 2MCA did not significantly impair mitochondrial glutamate transport. Finally, 2MCA provoked a significant decrease in mitochondrial membrane potential and induced swelling in Ca(2+)-loaded mitochondria supported by different substrates. These effects were totally prevented by cyclosporine A plus ADP or ruthenium red, indicating induction of mitochondrial permeability transition. Taken together, our data strongly indicate that 2MCA behaves as a potent inhibitor of glutamate oxidation by inhibiting glutamate dehydrogenase activity and as a permeability transition inducer, disturbing mitochondrial energy homeostasis. We presume that 2MCA-induced mitochondrial deleterious effects may contribute to the pathogenesis of brain damage in patients affected by methylmalonic and propionic acidemias. We propose that brain glutamate oxidation is disturbed by 2-methylcitric acid (2MCA), which accumulates in tissues from patients with propionic and methylmalonic acidemias because of a competitive inhibition of glutamate dehydrogenase (GDH) activity. 2MCA also induced mitochondrial permeability transition (PT) and decreased ATP generation in brain mitochondria. We believe that these pathomechanisms may be involved in the neurological dysfunction of these diseases. | 10.1111/jnc.13544 |
pubmed_591_25633 | The obligate intracellular pathogen Lawsonia intracellularis (LI), the etiological agent of proliferative enteropathy (PE), poses a substantial economic loss in the swine industry worldwide. In this study, we genetically engineered an O-antigen-deficient (rough) Salmonella strain secreting four selected immunogenic LI antigens, namely OptA, OptB, LfliC, and Lhly. The genes encoding these antigens were individually inserted in the expression vector plasmid pJHL65, and the resultant plasmids were transformed into the ∆asd ∆lon ∆cpxR ∆rfaL Salmonella Typhimurium (ST) strain JOL1800. The individual expression of the selected LI antigens in JOL1800 was validated by an immunoblotting assay. We observed significant (P < 0.05) induction of systemic IgG and mucosal IgA responses against each LI antigen or Salmonella outer membrane protein in mice immunized once orally with a mixture of four JOL1800-derived strains. Further, mRNA of IL-4 and IFN-γ were highly upregulated in splenic T cells re-stimulated in vitro with individual purified antigens. Subsequently, immunized mice showed significant protection against challenge with 106.9 TCID50 LI or 2 × 109 CFU of a virulent ST strain. At day 8 post-challenge, no mice in the immunized groups showed the presence of LI-specific genomic DNA (gDNA) in stool samples, while 50% of non-immunized mice were positive for LI-specific gDNA. Further, all the immunized mice survived the virulent ST challenge, compared to a 20% mortality rate observed in the control mice. Collectively, the constructed rough ST-based LI vaccine candidate efficiently elicited LI and ST-specific humoral and cell-mediated immunity and conferred proper dual protection against PE and salmonellosis. | 10.1186/s13567-018-0552-8 |
pubmed_330_15529 | JC virus (JCV) is a neurotropic polyomavirus and the causative agent of progressive multifocal leukoencephalopathy. A role for JCV in gastrointestinal malignancies has been recently suggested. This study was carried out to determine the prevalence of polyomaviruses including JCV, BKV and SV40 in gastric cancers in Tunisia and to determine the clinicopathological characteristics of virus-associated gastric carcinomas. The presence of polyomaviruses DNA sequences was surveyed in 61 cases of primary gastric carcinomas and in 53 paired non-tumor gastric mucosa by PCR. Findings were correlated to clinicopathological parameters, p53 expression and methylation status of 11 tumor-related genes. Using PCR assays, JCV T-antigen sequence was more frequently detected in gastric carcinomas than in non-tumor gastric mucosa (26 vs 6%, P=0.03), while those of SV40 and BKV were not detected in any cases. Correlation analysis showed that JCV had higher frequency in patients older than 55 years (P=0.034) and in the intestinal histological type (P=0.04). With regard to methylation status, P16 and P14 showed significantly higher methylation frequencies in JCV-positive gastric carcinomas than in JCV-negative cases (P=0.007 and P=0.003, respectively). Moreover, the mean of the methylation index was significantly higher in JCV-positive than in JCV-negative cases (P=0.024). In multivariate logistic regression analysis, age of patients and the methylation index are only the two independent factors associated with JCV infection. Kaplan-Meier survival analysis showed a trend toward better survival for JCV-associated gastric carcinomas patients (log-rank, P=0.11). Our study suggests a role of JCV as cofactor in the pathogenesis of the intestinal type of gastric carcinomas in older persons. | 10.1038/modpathol.2009.184 |
pubmed_458_20907 | We document an echovirus 18 meningitis outbreak occurring at a remote overnight children's camp in Alaska. The outbreak involved 26% of 113 camp residents, was associated with building overcrowding and occurred in a camp with a contaminated drinking water source. Lack of specific children's camp regulations and failure to implement and enforce existing regulations may have contributed to the outbreak. | 10.1097/01.inf.0000136867.18026.22 |
pubmed_436_15202 | OBJECTIVE
To determine the circumstances under which sodium chloride injection (SCI) that has been exposed to fluorescent light then used to prepare 99m Tc-MAG3 causes low radiochemical purity (RCP).
METHODS
Two brands of SCI in plastic ampoules (Braun and Steri-Amp) and one in glass vials (Drytec) were exposed to light for up to 7 days then used to prepare 99m Tc-MAG3. RCP was measured by liquid chromatography. To study the effect on the labelling reaction, the reconstituted MAG3 kit was analysed before and after boiling and the formation of the 99m Tc-tartrate intermediate was investigated. Exposed water from plastic ampoules was analysed by mass spectrometry.
RESULTS
After no exposure, each brand resulted in high RCP 99m Tc-MAG3 (>94%). Drytec SCI produced high RCP throughout (96.7 +/- 0.3%, n=5, 7 days). The RCP produced by Steri-Amp and Braun fell to 85.2 +/- 5.2% and 93.5 +/- 1.6% after exposure for 2 and 4 days, respectively. The chromatogram before boiling contained peaks corresponding to 99m Tc-tartrate and 99m Tc-pertechnetate. After boiling with unexposed SCI, these were minimal and a 99m Tc-MAG3 peak dominated. After boiling with exposed SCI, 99m Tc-pertechnetate and 99m Tc-MAG3 peaks were present. Measurements on tartrate showed a high level of 99m Tc-tartrate before and after boiling with unexposed SCI but a high level of 99m Tc-pertechnetate after boiling with exposed SCI. Mass spectrometry showed that compounds leach into the solution upon exposure to light.
CONCLUSION
Preparing 99m Tc-MAG3 using SCI from plastic ampoules that have been exposed to light causes reduced RCP. Exposure of plastic ampoules to light causes leaching of many compounds into the solution. An unknown leached compound destabilizes the 99m Tc-tartrate intermediate complex. | 10.1097/MNM.0b013e3282f63552 |
pubmed_786_11800 | Reductive dechlorination of individual PCB congeners in Aroclor 1248 was investigated using sediment microorganisms from the St. Lawrence River (NY). No dechlorination was observed at Aroclor concentrations below 40 ppm [137 nmol (g of sediment)(-1)]. Above this threshold, congeners could be divided into three categories: group A, congeners that dechlorinated above 40 ppm; group B, congeners that dechlorinated only at high concentrations above 60 ppm [206 nmol (g of sediment)(-1)]; and group C, lower chlorinated congeners that increased in concentration. The dechlorination rate of congeners in groups A and B was a linear function of their initial sediment concentration. For group A congeners, the concentration intercepts of this linear function were the same as their concentrations in the Aroclor at the threshold concentration, and these therefore represented the threshold values. However, the intercepts of group B congeners were significantly higher than their levels at the threshold Aroclor concentration and were equivalent to their concentrations in Aroclor 1248 at about 75 ppm [258 nmol (g of sediment)(-1)]. The final concentrations of group A and group B congeners at the end of dechlorination were the same, regardless of their initial concentrations. These final concentrations were significantly lower than their threshold values. The accumulation rate of group C congeners was a linear function of their initial concentrations, and the total accumulation was greater at higher Aroclor concentrations in sediments. | 10.1021/es034600k |
pubmed_548_22514 | α-synuclein is an abundant presynaptic protein that is important for regulation of synaptic vesicle trafficking, and whose misfolding plays a key role in Parkinson's disease. While α-synuclein is disordered in solution, it folds into a helical conformation when bound to synaptic vesicles. Stabilization of helical, folded α-synuclein might therefore interfere with α-synuclein-induced neurotoxicity. Here we show that several small molecules, which delay aggregation of α-synuclein in solution, including the Parkinson's disease drug selegiline, fail to interfere with misfolding of vesicle-bound α-synuclein. In contrast, the porphyrin phtalocyanine tetrasulfonate directly binds to vesicle-bound α-synuclein, stabilizes its helical conformation and thereby delays pathogenic misfolding and aggregation. Our study suggests that small-molecule-mediated stabilization of helical vesicle-bound α-synuclein opens new possibilities to target Parkinson's disease and related synucleinopathies. | 10.1038/ncomms6857 |
pubmed_235_25510 | Primary cilia play a pivotal role in signal transduction and development and are known to serve as signaling hubs. Recent studies have shown that primary cilium dysfunction influences adipogenesis, but the mechanisms are unclear. Here, we show that mesenchymal progenitors C3H10T1/2 depleted of trichoplein, a key regulator of cilium formation, have significantly longer cilia than control cells and fail to differentiate into adipocytes. Mechanistically, the elongated cilia prevent caveolin-1- and/or GM3-positive lipid rafts from being assembled around the ciliary base where insulin receptor proteins accumulate, thereby inhibiting the insulin-Akt signaling. We further generate trichoplein knockout mice, in which adipogenic progenitors display elongated cilia and impair the lipid raft dynamics. The knockout mice on an extended high-fat diet exhibit reduced body fat and smaller adipocytes than wild-type (WT) mice. Overall, our results suggest a role for primary cilia in regulating adipogenic signal transduction via control of the lipid raft dynamics around cilia. | 10.1016/j.celrep.2021.108817 |
pubmed_166_16099 | We consider two modifications of a recently proposed three-terminal quantum dot heat engine. First, we investigate the necessity of the thermalization assumption, namely that electrons are always thermalized by inelastic processes when traveling across the cavity where the heat is supplied. Second, we analyze various arrangements of tunneling-coupled quantum dots in order to implement a transmission function that is superior to the Lorentzian transmission function of a single quantum dot. We show that the maximum power of the heat engine can be improved by about a factor of two, even for a small number of dots, by choosing an optimal structure. | 10.1088/1361-648X/aa5140 |
pubmed_44_24008 | The developmental rate of a blastocyst is considered one of the main estimates for evaluating the implantation potential of embryos. Day 6 blastocysts have been reported to be much less viable than day 5 blastocysts. Regarding implantation, the implantation window is advanced due to a background of high sex hormones, and slower growing embryos may not implant because of possible desynchrony with the implantation window. The aim of this study was to investigate the efficacy of cryopreservation of such embryos and subsequent synchronization of embryo transfer with endometrial status. The results of 122 day 6 blastocysts transferred in the clinic were retrospectively examined. Pregnancy rates were compared between the stimulation cycle and hormone replacement cycle in terms of the method of endometrial preparation. Fifty-five day 6 blastocysts were transferred onto the stimulation cycle endometrium in 37 women, resulting in a 5.5% viable pregnancy rate. On the other hand, 67 day 6 blastocysts were transferred onto endometrium prepared by exogenous hormones in 40 women, resulting in a 26.9% viable pregnancy rate (P < 0.01). Consequently, the difference was highly significant. In conclusion, synchronous transfer of slow-growing embryos using the freeze-thaw technique contributes to a positive outcome. | 10.1016/s1472-6483(10)61134-0 |
pubmed_60_25741 | The community nurse will encounter many queries and requests for advice in the work environment. This article offers information on diet related to the stoma. Specific advice for the three different types of stoma, and for certain situations that might arise after the ostomate (person with a stoma) is discharged home, is provided. Much of the advice is common sense, but it might prevent the use of medication such as laxatives. Nutrition is essential for recovery following surgery and in the long-term. By using the information provided, the community nurse can give better care to this group of patients. | 10.12968/bjcn.2011.16.10.479 |
pubmed_1110_24062 | Community-based participatory research (CBPR) answers the call for more patient-centered, community-driven research approaches to address growing health disparities. CBPR is a collaborative research approach that equitably involves community members, researchers, and other stakeholders in the research process and recognizes the unique strengths that each bring. The aim of CBPR is to combine knowledge and action to create positive and lasting social change. With its origins in psychology, sociology, and critical pedagogy, CBPR has become a common research approach in the fields of public health, medicine, and nursing. Although it is well aligned with psychology's ethical principles and research aims, it has not been widely implemented in psychology research. The present article introduces CBPR to a general psychology audience while considering the unique aims of and challenges in conducting psychology research. In this article, we define CBPR principles, differentiate it from a more traditional psychology research approach, retrace its historical roots, provide concrete steps for its implementation, discuss its potential benefits, and explore practical and ethical challenges for its integration into psychology research. Finally, we provide a case study of CBPR in psychology to illustrate its key constructs and implementation. In sum, CBPR is a relevant, important, and promising research framework that may guide the implementation of more effective, culturally appropriate, socially just, and sustainable community-based psychology research. (PsycINFO Database Record (c) 2018 APA, all rights reserved). | 10.1037/amp0000167 |
pubmed_893_5461 | Transplantation of cryopreserved ovarian tissue has been considered as a promising way of fertility preservation for women. however, this cryopreservation method is prone to post-resuscitation follicle proliferation and oocyte development stagnation, affecting late transplant survival. To evaluate current vitrification works, we investigated the critical pathway alternations in vitrified-warmed juvenile 10-day-old mouse ovary. We showed a significant decrease of protein kinase B (Akt) and Mitogen-activated protein kinase (Mapk) phosphorylation, during which serine/threonine kinases play central roles in coordinating follicle and oocyte development and stress response. Inhibition of Akt and Mapk activity were associated with one of the imprinted insulin pathway negative regulatory genes, Growth factor receptor-binding protein 10 (Grb10) which remarkably increased in vitrified-warmed juvenile mouse ovary than that of fresh group (p < 0.05). RNAi-induced Grb10 down-regulation reversed the decrease in Akt and Mapk phosphorylation. The increase of Grb10 expression was partially caused by the hyper-methylation of the promoter region, associated with the decrease of follicular DNA methyltransferase (Dnmt) 1 protein in different stages of vitrified-warmed group, compared to fresh group (p < 0.05). The mRNA and protein expression of Dnmt1 in ovary of vitrified-warmed juvenile mouse were remarkably lower than those in fresh group (p < 0.05). Dnmt1 overexpression dramatically reversed Grb10 up-regulation and Akt and Mapk phosphorylation reduction. Taken together, our findings suggest that Grb10 expression might be helpful in evaluation of effectiveness of vitrification, and considered as a potential target for further vitrification protocols improvement in the future. | 10.1016/j.cryobiol.2017.11.008 |
pubmed_25_389 | Orientation in the monopolar pulse field used as the unconditioned stimulus was found to influence formation of a conditioned response to light in planarians. Planarians trained while oriented with the head toward the cathode reached maximal response rates rapidly, while those trained while oriented toward the anode showed no evidence of conditioned response formation. | 10.1126/science.141.3582.728 |
pubmed_167_5831 | The diamondback moth, Plutella xylostella (Linnaeus), is one of the notorious pests causing substantial loses to many cruciferous vegetables across the nations. Sterile insect technique (SIT) is considered as an effective bio-control agent for controlling numerous lepidopteran pests. We searched the deformity spermatozoon and sperm bundles of diamondback moth. In our research, 200 Gy and 400 Gy 60Co-γ radiation doesn't alter the number of apyrene and eupyrene sperm bundles in testis. However, the ratio of abnormal eupyrene sperm bundles was increasing with radiation dosage. The malformation of mitochondrial derivatives is characterized by "V" shape with 400 Gy. Also, the results showed that the expression of caspase-3 with 200 Gy was down-regulated, but was obviously up-regulated after 400 Gy radiation. Thus the present research investigation highlights that the 60Co-γ radiation treatments alters the physiological development of diamondback moth testis. | 10.1016/j.ecoenv.2018.11.028 |
pubmed_960_15763 | A fugacity-based, nonsteady state, mechanistic model called ACC-HUMAN was developed to describe bioaccumulation of lipophilic organic pollutants from air, water, and soil to humans. The physical environment was linked via a marine and an agricultural food chain model to a human bioaccumulation model. Contaminant uptake via the primary dietary sources of persistent lipophilic contaminants in industrialized countries was addressed, namely fish, dairy products, and beef. In addition, uptake from air and water was considered, allowing the model also to treat less lipophilic compounds. To evaluate the model, the food chain characteristics were parameterized for southern Sweden and historical scenarios of polychlorinated biphenyl (PCB) concentrations in air, water, and soil in this region were constructed from published data. The resulting model predictions of PCB concentrations in fish, milk, beef, and human tissue agreed well with measured concentrations from Swedish monitoring programs. This suggests that ACC-HUMAN is a useful tool for predicting human exposure to bioaccumulative organic compounds. It can be linked easily to existing multimedia fate and transport models. | 10.1897/03-317 |
pubmed_239_3627 | Contributing to recent scholarship on the governance of algorithms, this article explores the role of dignity in data protection law addressing automated decision-making. Delving into the historical roots of contemporary disputes between information societies, notably European Union and Council of Europe countries and the United States, reveals that the regulation of algorithms has a rich, culturally entrenched, politically relevant backstory. The article compares the making of law concerning data protection and privacy, focusing on the role automation has played in the two regimes. By situating diverse policy treatments within the cultural contexts from which they emerged, the article uncovers and examines two different legal constructions of automated data processing, one that has furnished a right to a human in the loop that is intended to protect the dignity of the data subject and the other that promotes and fosters full automation to establish and celebrate the fairness and objectivity of computers. The existence of a subtle right across European countries and its absence in the US will no doubt continue to be relevant to international technology policy as smart technologies are introduced in more and more areas of society. | 10.1177/0306312717699716 |
pubmed_294_23389 | Triple-helical structures involving the interaction of an oligonucleotide third strand with a duplex nucleic acid sequence have recently gained attention as a therapeutic strategy in the "antigene" approach [cf. Helene, C. (1991) Eur. J. Cancer 27, 1466-1471]. This method utilizes the triple helix formed from the cellular duplex and an added third strand to directly regulate the activity of a selected gene. The limited stability of nucleic acid triple-helical interactions, particularly if the third strand has backbone modifications such as methylphosphonate or phosphorothioate substitutions, is a limiting condition for the use of this approach. We have designed and synthesized compounds, on the basis of the following three criteria, that we feel should provide selective interactions and significant stabilization of triplexes: appropriate aromatic surface area for stacking with triplex bases in an intercalation complex, positive charge, and limited torsional freedom in the aromatic system to match the propeller twist of the triple-base interactions in the triplex. A series of quinoline derivatives with an alkylamine side chain at the 4-position and with different aryl substituents at the 2-position has been synthesized as our first compounds. A 2-naphthyl derivative provides significant and selective stabilization of the triplex. In a 0.2 M NaCl buffer, the naphthyl derivative increased the Tm for the triplex (triplex to duplex and third strand transition) by approximately 30 degrees C more than the Tm increase for the duplex (duplex to single strands transition). Spectral changes and energy-transfer results indicate that the naphthyl compound and related derivatives bind to the triplex by intercalation.(ABSTRACT TRUNCATED AT 250 WORDS) | 10.1021/bi00091a011 |
pubmed_254_3134 | Brain glia produce neuroactive metabolites via tryptophan-kynurenine catabolism. A role for kynurenine pathway (KP) metabolites is proposed in reactive glial associated neurodegeneration. The aim of this investigation was to assess the role of KP induction and KP metabolites in driving reactive glial associated neuronal atrophy. Rat primary mixed glia, and enriched microglial and astroglial cultures were stimulated with IFNγ (10 ng/ml) for 24 hours. KP induction in mixed glial cells was confirmed by raised expression of the rate limiting KP enzyme indoleamine 2,3 dioxygenase (IDO) and raised concentrations of KP metabolites kynurenic acid (KYNA) and quinolinic acid (QUIN) in the conditioned media. Conditioned media was transferred onto immature (3 days) and mature (21 days) primary cortical neurons in vitro for 24 hours. IFNγ-stimulated mixed glial conditioned media reduced neurite outgrowth and complexity of both immature and mature neurons and co-localised expression of synaptic markers determined by immunocytochemistry. Pre-treatment of mixed glial cells with the IDO inhibitor, 1-methyltryptophan (1-MT) (L) prevented these effects of IFNγ-stimulated mixed glial conditioned media. KYNA increased complexity and synapse formation in mature cortical neurons and protected against reduced neuronal complexity and co-localised expression of synaptic markers induced by conditioned media from IFNγ-stimulated mixed glia and by treatment of neuronal cells with QUIN (1 µM). Overall, this study supports a role for the KP in driving neuronal atrophy associated with reactive glia and indicates that inhibition of the KP in glia, or raising the concentration of the astrocytic metabolite KYNA, protects against reactive microglial and QUIN-associated neuronal atrophy. | 10.1007/s11481-020-09976-x |
pubmed_278_3560 | BACKGROUND : Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is recommended for the diagnosis of solid pancreatic masses. We aimed to evaluate whether a high needle movement acceleration value during puncture increases diagnostic accuracy. METHODS : EUS-FNA needle acceleration was measured using a PocketLab accelerometer connected by Bluetooth to a smartphone. Two passes (fast and slow, with higher and lower than 1g [9.8 m/s2] needle acceleration values, respectively) were performed in a random order. The sample cellularity and quality were measured using semiquantitative scales. RESULTS : 51 patients were included (32 women; mean age 63). The mean (standard deviation [SD]) acceleration values were 1.59g (0.66g) for the fast pass and 0.32g (0.19g) for the slow pass (P < 0.001). The fast pass yielded significantly higher levels of EUS-FNA accuracy (84.3 % vs. 68.6 %; P = 0.02) and adequate quality scores (94.1 % vs. 76.5 %; P = 0.007). High cellularity scores were seen with similar frequencies (15.7 % vs. 11.8 %; P = 0.32). CONCLUSIONS : A higher than 1g EUS-FNA needle acceleration may increase the diagnostic accuracy and specimen quality from solid pancreatic lesions. | 10.1055/a-1497-6532 |
pubmed_688_1273 | A slow clotting dysfibrinogen with delayed anodal immunoelectrophoretic mobility and impaired fibrinopeptide A release has been identified in a patient with recurrent portal vein and deep venous thrombosis. Affected family members tested in the initial screening were asymptomatic. The proband's father died of pulmonary embolism at age 44 years and had mesenteric thrombosis at necropsy. The association of a plasma protein abnormality with visceral thrombosis is unusual and has never been observed previously with a dysfibrinogen. The qualitative abnormality is transmitted as an autosomal codominant and is tentatively designated, fibrinogen Irvine. | pubmed_688_1273 |
pubmed_418_6830 | BACKGROUND
Molding helmet therapy is used for the treatment of infants with deformational brachycephaly (DB). There is a lack of rigorous outcome measures of helmet therapy in patients with DB using 3-dimensional (3D) imaging, with most reports rely on either subjective or 2-dimensional analyses. Furthermore, the longitudinal assessment of head shape improvement over the course of helmet therapy has not been documented. Our goal was to assess the outcome of molding helmet therapy using 3D surface imaging, and to document the pace of improvement during treatment.
METHODS
The head shape of 18 infants with DB who underwent orthotic molding helmet therapy was assessed. The 3D scans were obtained before treatment, during treatment, and at the end of treatment. First, we applied shape analysis techniques based on template deformation to obtain average (composite) heads of the 18 patients at the 3 time points of treatment (pretreatment, during, and posttreatment). In addition, we used 3D curvature analysis to quantify the degree of flatness at the same time points.
RESULTS
Molding helmet therapy started at 6.7 ± 0.9 months of age and lasted for 4.3 ± 0.8 months. The overall difference in the occipital contour between pretreatment and end of treatment was 6.3 ± 1.7 mm. Curvature analysis revealed that 15% of the back of the head had prehelmet marked flatness (mean curvature <5/m), which decreased to 9% at 2.5 months into treatment and 7% at the end of treatment.
CONCLUSION
Over 65% of the head shape improvement occurred during the 2.5 months of molding helmet therapy. | 10.1097/SCS.0000000000005611 |
pubmed_762_19155 | Engraftment failure following allogeneic bone marrow (BM) transplantation is of clinical concern particularly involving T-cell-depleted inoculum and transplantations for aplastic anemia. Immune resistance by lymphoid and natural killer (NK) populations with "barrier" function is well established. Major histocompatibility complex (MHC)-identical marrow allografts were examined to investigate effector pathways in non-NK-mediated resistance. Barrier function was examined in cytotoxic normal and deficient B6 (H-2(b)) recipients primed to donor minor histocompatibility antigen (MiHA) prior to BM transplantation. Host resistance was sensitively evaluated by colony-forming unit (CFU) assays to directly assess for donor progenitor cell (PC) and peripheral chimerism. B6 host CD8(+) T cells but not CD4(+) or NK1.1(+) cells effected rejection of primitive (CFU-HPP [high-proliferative potential]) and lineage-committed (CFU-IL3/GM [interleukin 3/granulocyte macrophage]) allogeneic donor progenitors. To address complementation by the cytotoxic pathways existing in singly deficient (perforin or FasL) recipients, cytotoxically double (perforin plus FasL) deficient (cdd) recipients were used. Resistance in B6-cdd recipients was comparable to that of wild-type B6 recipients and was also dependent on CD8(+) T cells. A "triple" cytotoxic deficient model, involving transplantation of TNFR1(-/-) (tumor necrosis factor receptor 1) progenitor grafts did not diminish the ability of B6-cdd recipients to reject allografts. Finally, injection of anti-TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) monoclonal antibody (mAb) in B6-cdd recipients also failed to inhibit rejection of TNFR1(-/-) marrow grafts. In total, these studies demonstrate that CD8(+) host T cells can effectively resist MHC-matched MiHA-mismatched donor PCs via alternative effector pathway(s) independent of perforin-, FasL-, TNFR-1-, and TRAIL-dependent cytotoxicity. Therefore, inhibition of these effector pathways in sensitized recipients is unlikely to result in stem cell engraftment following PC allografts. | 10.1182/blood-2002-09-2859 |
pubmed_128_8892 | BACKGROUND
Unsafe abortion is one of the greatest neglected problems of health care in developing countries like Pakistan. In countries where abortions are restricted women have to resort to clandestine interventions to have an unwanted pregnancy terminated. The study was conducted to find out the prevalence of septic induced abortion and the associated morbidity and mortality and to highlight the measures to reduce it.
METHODS
This cross-sectional descriptive study was carried out in Obs/Gyn B Unit, Ayub Teaching Hospital, Abbottabad from January 2007 to December 2011. During this period all the patients presenting with pyrexia lower abdominal pain, vaginal bleeding, acute abdomen, septic or hypovolaemic shock after undergoing some sort of intervention for abortion outside the hospital were included. After thorough history, examination and detailed investigations including high vaginal and endocervical swabs for culture and sensitivity and pelvic ultrasound supportive management was given followed by antibiotics, surgical evacuation of uterus/ major laparotomy in collaboration with surgeon as required. Patients with DIC or multiple system involvement were managed in High Dependency Unit (HDU) by multidisciplinary team.
RESULTS
During the study period out of a total 6,906 admissions 968 presented with spontaneous abortion. There were 110 cases (11.36%) of unsafe abortion, 56.4% presented with vaginal discharge, 34.5% with vaginal bleeding, 21.8% with acute abdomen, while 18.9% in shock and 6.8% with DIC. Forty-nine percent patients used termination as a method of contraception. Mortality rate was 16.36%, leading cause being septicaemia.
CONCLUSION
Death and severe morbidity from unsafe abortions and its complications is avoidable through health education, effective contraception, early informed recognition and management of the problem once it occurs. | pubmed_128_8892 |
pubmed_588_3365 | AIM
To relate the endoscopic findings in patients with hematochezia with regard to age in "low and average risk" for colorectal cancer (CRC) and to localize significant lesions in order to identify patients who need sigmoidoscopy or total colonoscopy.
METHODS
This prospective study was performed in an open access GI endoscopy unit. Out of 4322 consecutive patients undergoing colonoscopy, 918 reported hematochezia. The final study group comprized 180 patients aged below 45 and 237 over 45. Main exclusion criteria were a 1st-degree family history of colorectal carcinoma, patients reporting blood mixed with stools and/or progressive colonic symptoms, or patients who had undergone colon surgery for neoplastic lesions.
RESULTS
Total colonoscopy could be performed in 96% of patients. Abnormal findings were observed in 34.3% of the younger and in 65.7% of the older ones. Findings were the presence of polyps in the distal colon (n = 2) and IBD in the proximal colon (n = 29) in the group of the younger patients, and polyps (n = 15), IBD (n = 13), and carcinoma (n = 6, 4 of the lesions were located proximal to the splenic flexure) in the elderly. Our findings suggest that the diagnostic potential of total colonoscopy in patients younger than 45 referring scant hematochezia, is not mandatory. By exploring only the distal tract of the colon we have misdiagnosed two cases of IBD located in the ascending colon. In this group of patients additional risk factors must be identified before performing a total colonoscopy. Regarding the patients older than 45 yr, the exploration of the distal colon would have led to our overlooking a carcinoma, two neoplastic polyps and one IBD located in the proximal colon.
CONCLUSION
Young patients with scant hematochezia but without risk factors for neoplasia do not need a total colonoscopy, whereas is mandatory performing a total colonoscopy in older patients even in the presence of anal pathology. | 10.3748/wjg.v12.i45.7304 |
pubmed_815_13145 | Potential pitfalls in the multivariate analysis of data, and methods of overcoming such problems, are illustrated by reference to recent research that has examined relationships between fitness variables and overall productivity in a population of young male paraplegics. Particular attention is directed to the need for residual analysis, tests of multiple collinearity, and a cautious approach to interpreting the theoretical meaning of individual coefficients in multiple regression equations. | pubmed_815_13145 |
pubmed_569_21516 | INTRODUCTION
Surgical performance is affected by distractors and interruptions to surgical workflow that exist in the operating room. However, traditional surgical simulators are used to train surgeons in a skills laboratory that does not recreate these conditions. To overcome this limitation, we have developed a novel, immersive virtual reality (Gen2-VR) system to train surgeons in these environments. This study was to establish face and construct validity of our system.
METHODS AND PROCEDURES
The study was a within-subjects design, with subjects repeating a virtual peg transfer task under three different conditions: Case I: traditional VR; Case II: Gen2-VR with no distractions and Case III: Gen2-VR with distractions and interruptions. In Case III, to simulate the effects of distractions and interruptions, music was played intermittently, the camera lens was fogged for 10 s and tools malfunctioned for 15 s at random points in time during the simulation. At the completion of the study subjects filled in a 5-point Likert scale feedback questionnaire. A total of sixteen subjects participated in this study.
RESULTS
Friedman test showed significant difference in scores between the three conditions (p < 0.0001). Post hoc analysis using Wilcoxon signed-rank tests with Bonferroni correction further showed that all the three conditions were significantly different from each other (Case I, Case II, p < 0.0001), (Case I, Case III, p < 0.0001) and (Case II, Case III, p = 0.009). Subjects rated that fog (mean 4.18) and tool malfunction (median 4.56) significantly hindered their performance.
CONCLUSION
The results showed that Gen2-VR simulator has both face and construct validity and that it can accurately and realistically present distractions and interruptions in a simulated OR, in spite of limitations of the current HMD hardware technology. | 10.1007/s00464-015-4278-7 |
pubmed_970_17391 | Endovascular aneurysm repair (EVAR) is now considered the first choice treatment modality for abdominal aortic aneurysm (AAA) treatment. Advocates for endovascular strategies will try to treat all AAA by EVAR, regardless if the anatomy is conducive for treatment or not. However, the long-term outcomes of EVAR outside the instructions for use (IFU) due to a hostile aneurysmal neck or iliac artery anatomy are known to be poor. The EVAR procedures can be classified according to the technical difficulty, IFU, and need for visceral revascularization: standard, adjunctive, and complex EVAR. The situation required for adjunctive procedures can be classified as the following four steps: a hostile neck (i.e., short or severely angled); large inferior mesenteric or lumbar artery; tough iliac artery anatomy, such as a short common iliac artery and stenotic external iliac artery; and limitations in vascular access. This article will discuss the adjunctive procedures to overcome hostile aneurysm neck and unsuitable iliac artery anatomy. | 10.5758/vsi.2020.36.1.7 |
pubmed_638_6859 | This review starts from a brief historical account devoted to the principles of the Bach-Engler peroxidation theory and experiments and ideas which led A. N. Bach to its creation. Then, the discovery of photodynamic action is described, which was shown to result from pigment photosensitized activation of molecular oxygen. The dramatic history of mechanistic studies of oxygen photoactivation is reviewed starting from the Bach-Engler peroxidation theory to the hypothesis of moloxide, discovery of singlet oxygen and free radicals and, then, to modern views on the primary photoactivation processes. The origin of widely used division of photodynamic processes into type I and type II and the relation of these processes to the nature of the primary photochemical reactions of photosensitizers are discussed. New definitions of these reactions are proposed on the basis of the mechanisms of oxygen photoactivation. Photographs of the scientists who greatly contributed to the development of this field of research are presented. | 10.1134/s0006297907100057 |
pubmed_44_22860 | Escherichia coli is a common inhabitant of the intestinal tracts of animals and humans. The intestines of animals also represent an ideal environment for the selection and transfer of antimicrobial resistance genes. The aim of this study was to investigate the resistance of E. coli isolated from chicken fecal samples to fluoroquinolones and to analyze the characterization of mutations in its gyrA and parC gene related resistance. One hundred and twenty-eight E. coil isolates showed a high resistance to ciprofloxacin (CIP; 60.2%), enrofloxacin (ENO; 73.4%) and norfloxacin (NOR; 60.2%). Missense mutation in gyrA was only found in the amino acid codons of Ser-83 or Asp-87. A high percentage of isolates (60.2%) showed mutations at both amino acid codons. Missense mutation in parC was found in the amino acid codon of Ser-80 or Glu-84, and seven isolates showed mutations at both amino acid codons. Isolates with a single mutation in gyrA showed minimal inhibitory concentrations (MIC) for CIP (<or=0.5 to 0.75 microg/ml), ENO (1 to 4 microg/ml) and NOR (0.75 to 4 microg/ml). These MIC were level compared to isolates with two mutations, one in gyrA and one in parC, and three mutations, one in gyrA and two in parC (CIP, <or=0.5 to 3 microg/ml; ENO, 2 to 32< microg/ml; NOR, 1.5 to 6 microg/ml). However, the isolates with two mutation in gyrA regardless of whether there was a mutation in parC showed high MIC for the three fluoroquinolones (CIP, 0.75 to 32 <or=microg/ml; ENO, 3 to 32 <or=microg/ml; NOR, 3 to 32 <or=microg/ml ). Interestingly, although the E. coil used in this study was isolated from normal flora of chicken, not clinical specimens, a high percentage of isolates showed resistance to fluoroquinolones and possessed mutations at gyrA and parC associated with fluoroquinolone resistance. | pubmed_44_22860 |
pubmed_698_7219 | AIMS
The best known and probably most important mechanism of health-protective moderate alcohol drinking is beneficial changes in plasma lipid levels. We determined changes in main plasma lipid levels in alcohol-dependent patients over a 6-month abstinence period.
METHODS
Fifty-four alcohol-dependent male patients, who were abstinent for less than 14 days, and 20 non-alcoholic males, who had not drunk alcohol for the last month, were studied. In all patients at the study start and after 4 weeks and 6 months observation, lipoprotein(a) [Lp(a)], total cholesterol (TC), HDL cholesterol (HDL), LDL cholesterol (LDL) and triglyceride concentrations, both fasting and 5 h after a fatty meal, were determined.
RESULTS
Alcohol-dependent patients had similar mean fasting and post-prandial plasma lipid levels as the control group, both at the study start and after 4 weeks of abstinence. Whereas, in alcohol-dependent patients after 4 weeks of abstinence, a significant decrease in Lp(a) and fasting HDL levels, as well as a significant increase in fasting LDL level and pro-atherogenic indices of plasma lipids [TC/HDL, (TC-HDL)/HDL, LDL/HDL, Lp(a)/HDL] were observed. Post-prandial levels of studied plasma lipids, except HDL, did not change over the 6-month observation period. In patients who did not remain abstinent for the whole observation period (n = 9), in comparison to abstinent patients, significantly higher HDL levels and a tendency to higher values of LDL, LDL/HDL, Lp(a) and Lp(a)/HDL were found.
CONCLUSIONS
(1) Higher Lp(a) levels soon after alcohol withdrawal may be a factor potentially responsible for the increase of acute cardiac syndromes prevalent in the drinking and early abstinence period, in spite of high HDL concentration; (2) in alcohol-dependent male patients, after a 6-month abstinence period, pro-atherogenic plasma cholesterol fraction changes occurred, expressed by a decrease in HDL level and an increase in LDL concentration. | 10.1093/alcalc/agg045 |
pubmed_373_9719 | Infection by human immunodeficiency virus type 1 (HIV-1) results in a progressive depletion of CD4+ T lymphocytes, leading to fatal immunodeficiency. The mechanisms causing the marked loss of CD4+ T lymphocytes are incompletely understood. However, several lines of evidence indicate that direct cytopathology mediated by HIV-1 is a key element in such CD4+ T-cell depletion. In this study, we investigated whether the previously reported incorporation of host-derived major histocompatibility class II glycoproteins (MHC-II) on HIV-1 can alter its replicative capacity. To achieve this goal, virus stocks were produced in parental MHC-II-expressing RAJI cells and in MHC-II-negative RAJI mutants (RM3), both of which have been stably transfected with human CD4 cDNA to allow productive infection with HIV-1. An enhancement of the rate/efficiency of virus entry was seen after infection with normalized amounts of virions carrying host-derived MHC-II on their surface as compared with inoculation with virions devoid of cellular MHC-II. Data from time-course and infectivity experiments showed that the kinetics of infection were more rapid for virions bearing host-derived MHC-II glycoproteins than for MHC-II-free HIV-1 particles. These results suggest that virally embedded cellular MHC-II glycoproteins are functional and can have a positive effect on early events in the virus replicative cycle. Therefore, we show that the acquisition of cellular MHC-II glycoproteins by HIV-1 can modify its biologic properties and might, consequently, influence the pathogenesis of this retroviral disease. | pubmed_373_9719 |
pubmed_1121_17502 | One third of depressive patients do not achieve remission after several steps of treatment and are considered as treatment resistant. Electroconvulsive therapy (ECT) improves symptoms in 70 to 90% of such cases. Resistant depression is associated with a dysregulation of the immune system with a dysbalance between the pro- and the anti-inflammatory cytokines. Therefore, we aimed to measure the kinetic of cytokines levels before, during and at the end of ECT. To test this hypothesis, we performed a meta-analysis assessing cytokines plasma levels before, during and after ECT in patients with major depressive disorders. After a systematic database search, means and standard deviations were extracted to calculate standardized mean differences. We found that IL-6 levels increased after 1 or 2 ECT session (p = 0.01) then decrease after 4 ECT sessions (p < 0.01) with no difference at the end of ECT (p = 0.94). A small number of studies were included and there was heterogeneity across them. The present meta-analysis reveals that ECT induces an initial increase of IL-6 levels and a potential decrease of TNF-α levels. No changes on IL-4 and IL-10 levels were found. Further work is necessary to clarify the impact of ECT on peripheral cytokines. | 10.1016/j.psychres.2021.113735 |
pubmed_537_12167 | Antibody to specific cell-wall carbohydrate of group A streptococci in human sera was determined by enzyme-linked immunosorbent assay (ELISA) with enzyme-treated whole cells and purified group A carbohydrate (ACHO) as antigens. The optimal concentration of enzyme-treated whole bacterial cells to coat wells was 2 x 10(8) cells/ml and for purified ACHO antigen the optimal concentration was 1 microgram/ml. Sera from patients with acute rheumatic fever and acute glomerulonephritis were screened for the presence of C-carbohydrate antibodies. Patients with acute post-streptococcal complications showed significantly higher titres of antibody when compared with normal healthy individuals. ELISA results were also compared with purified ACHO as an antigen; this showed a highly significant correlation (r = 0.73). Results showed that measurement of the anti-ACHO antibody by ELISA with enzyme-treated whole cells can be a useful, reliable and simple method for serological diagnosis of group A infection and sequelae. | 10.1099/00222615-45-3-214 |
pubmed_962_23726 | PTEN is frequently inactivated during the development of many cancers, including prostate cancer, and both bi-allelic and mono-allelic PTEN inactivation may contribute to tumorigenesis. PTEN mutations in clinical cancer specimens can easily be recorded but mono- or bi-allelic gene deletions are often difficult to assess. We performed a comprehensive study to detect PTEN inactivation in 40 locally progressive clinical prostate cancer specimens obtained by transurethral resection of the prostate, utilizing a variety of complementary technical approaches. The methods to detect PTEN deletion included allelotype analysis, dual-colour FISH and array-based CGH. We also applied a novel semi-quantitative approach, assessing the PTEN-WT (wild-type): PTEN-Psi (pseudogene) ratio (WPR). Structural analysis of PTEN was performed by single-strand conformational polymorphism (PCR-SSCP) and sequencing. PTEN protein expression was assessed by immunohistochemistry. Our data predict complete PTEN inactivation in 12 samples (30%), nine of these by bi-allelic deletion. Loss of one PTEN copy was also detected by several methodologies but the number could not be accurately assessed. Immunohistochemistry indicated the absence of PTEN protein in 15 samples, and heterogeneous expression of the protein in eight tumours. Taken together, these data show that bi-allelic deletion is a major mechanism of PTEN inactivation in locally progressive prostate cancer. | 10.1002/path.1929 |
pubmed_1097_18993 | CONTEXT
The Dreyfus model describes how individuals progress through various levels in their acquisition of skills and subsumes ideas with regard to how individuals learn. Such a model is being accepted almost without debate from physicians to explain the 'acquisition' of clinical skills.
OBJECTIVES
This paper reviews such a model, discusses several controversial points, clarifies what kind of knowledge the model is about, and examines its coherence in terms of problem-solving skills. Dreyfus' main idea that intuition is a major aspect of expertise is also discussed in some detail. Relevant scientific evidence from cognitive science, psychology, and neuroscience is reviewed to accomplish these aims.
CONCLUSIONS
Although the Dreyfus model may partially explain the 'acquisition' of some skills, it is debatable if it can explain the acquisition of clinical skills. The complex nature of clinical problem-solving skills and the rich interplay between the implicit and explicit forms of knowledge must be taken into consideration when we want to explain 'acquisition' of clinical skills. The idea that experts work from intuition, not from reason, should be evaluated carefully. | 10.3402/meo.v15i0.4846 |
pubmed_9_8997 | Data from a prospective study were used to investigate risk factors for hip fracture among a representative population of middle-aged adults. During the years 1974-1978, all women (n = 25,298) and men (n = 27,015) aged 35-49 years in three Norwegian counties were invited to attend a cardiovascular screening (attendance rate = 91.5%). This cohort was followed throughout 1990 with respect to hip fracture, for a total of 572,006 person-years. A total of 281 new fractures were identified, of which 71 were excluded from the analysis due to high-energy trauma or fracture in metastatic bone. Age-adjusted relative risks (RR) and 95% confidence intervals (CI) for hip fracture increased with body height in women (RR = 3.62, 95% CI 1.46-8.97, > or = 1.70 m vs. < 1.55 m) and men (RR = 2.92, 95% CI 0.94-9.05, > or = 1.85 m vs. < 1.70 m). A history of diabetes mellitus also gave elevated risk of fracture (RR = 5.81, 95% CI 2.15-15.71 in women and RR = 7.67, 95% CI 2.40-24.53 in men). In addition, hip fracture was related to body mass index (inverse), disability pension, and marital status. An increased risk for smokers appeared only among those consuming > or = 15 cigarettes per day. In multivariate analysis, all these risks remained elevated. This study suggests that, as in older populations, known risk factors for low bone mass are related to hip fracture among middle-aged adults. In addition, body height seems to have an independent influence on hip fracture incidence in this age group. | 10.1093/oxfordjournals.aje.a116622 |
pubmed_56_1405 | OBJECTIVES
To prospectively evaluate the immunogenicity of a 13-valent conjugated pneumococcal vaccine (PCV13) in rheumatoid arthritis (RA) patients undergoing etanercept therapy.
METHODS
Twenty-two RA patients treated with etanercept (ETA) in combination with methotrexate (MTX) (n=15) or monotherapy (n=7) for at least one year were included. Altogether 24 osteoarthritis patients not receiving biological or MTX therapy, treating only NSAIDs or analgesics served as controls. All subjects were vaccinated with a single dose (0.5ml) of the PCV13. Pneumococcal antibody levels at baseline, 4 and 8weeks were assessed by a VaccZyme™ Anti-PCP IgG Enzyme Immunoassay Kit. Based on recommendations of the American Academy of Allergy, Asthma & Immunology, an at least two-fold increase in antibody level, as the protective antibody response (pAR) was an indicator of responsiveness (i.e., ratio of postvaccination and prevaccination antibody levels). The antibody levels and their ratios were analysed in a variety of different ways, vaccine safety parameters (fever, infections, changes in regular antirheumatic treatments) were assessed at baseline, 4 and 8weeks after vaccination.
RESULTS
Four weeks after vaccination, the anti-pneumococcal antibody levels significantly increased in both groups. At week 8, antibody levels somewhat decreased in both groups, however, still remained significantly higher compared to baseline. Compared with postvaccination levels at 4 and 8weeks between two groups, the mean protective antibody levels were higher in control group (1st month P=0.016; 2nd month: P=0.039). Possible predictors of pAR were analysed by logistic regression model. In RA, increases of antibody levels at week 8 compared to baseline exerted a negative correlation with age, (Spearman's R=-0,431; P=0.045). There were no clinically significant side effects or reaction after administration of vaccine observed in any of these patients after the 2-month follow-up period, all patients medical condition were stable.
CONCLUSIONS
In RA patients treated with ETA, vaccination with PCV13 is effective and safe, resulting in pAR one and two months after vaccination. Higher age at vaccination was identified as predictors of impaired pAR. The efficacy of vaccination may be more pronounced in younger RA patients. The vaccine is safe in RA patients on ETA. | 10.1016/j.jbspin.2015.10.017 |
pubmed_983_15810 | The essential cofactors CoA, FAD and NAD+ are synthesized outside the peroxisomes and therefore must be transported into the peroxisomal matrix where they are required for important processes. In the present study we have functionally identified and characterized SLC25A17 (solute carrier family 25 member 17), which is the only member of the mitochondrial carrier family that has previously been shown to be localized in the peroxisomal membrane. Recombinant and purified SLC25A17 was reconstituted into liposomes. Its transport properties and kinetic parameters demonstrate that SLC25A17 is a transporter of CoA, FAD, FMN and AMP, and to a lesser extent of NAD+, PAP (adenosine 3',5'-diphosphate) and ADP. SLC25A17 functioned almost exclusively by a counter-exchange mechanism, was saturable and was inhibited by pyridoxal 5'-phosphate and other mitochondrial carrier inhibitors. It was expressed to various degrees in all of the human tissues examined. Its main function is probably to transport free CoA, FAD and NAD+ into peroxisomes in exchange for intraperoxisomally generated PAP, FMN and AMP. The present paper is the first report describing the identification and characterization of a transporter for multiple free cofactors in peroxisomes. | 10.1042/BJ20111420 |
pubmed_275_2957 | Dystonia refers to movement disorders characterized by sustained muscle contractions that produce abnormal postures, twisting movements, and other abnormal involuntary movements. A spectrum of etiologies underlies the various dystonia syndromes, ranging from genetic conditions to brain injury. First-line therapy for dystonia consists of pharmacologic agents of several classes and, particularly for focal dystonia, chemodenervation therapy with botulinum toxin. Many patients with dystonia realize an inadequate response to those treatments, and for such patients whose symptoms are sufficiently troublesome, surgical treatment can be used to reduce symptoms and improve function. Previously, the ablative procedures of thalamotomy and pallidotomy were used, in which a permanent destructive lesion was made in the motor territory of the thalamus or the globus pallidus. More recently, the device-based therapy of deep brain stimulation (DBS) has emerged as the preferred surgical treatment for dystonia and other movement disorders for most patients who require operative intervention. DBS uses a surgically implanted brain lead connected to an implanted neurostimulator to deliver chronic, high- frequency electrical stimulation to one of several deep nuclei. For dystonia, stimulation directed at the globus pallidus internus has been the most thoroughly studied to date. Advantages of DBS include its relatively non-destructive nature, its adjustability and reversibility, and its capacity to be used bilaterally in a safe manner. Use of DBS to treat dystonia is a rapidly evolving area, and preliminary evidence suggests that primary dystonia linked to genetic mutation, other primary dystonias, and tardive dystonic syndromes respond most dramatically to treatment with DBS, whereas secondary dystonia tends to be less responsive. | 10.1007/s11940-005-0017-z |
pubmed_458_5571 | In this study, we evaluated the performance of a digital chest imaging system using a contrast-detail (C-D) phantom. In the initial step, 76 sample images of the C-D phantom were produced by changing the doses from 0.5, 0.75, 1.0, 1.25, 1.5, to 2.0 times the dose for a screen-film (S/F) system. The sample images were analyzed by five radiological technologists and two medical physicists, and the image quality figure (IQF) was determined. The quality of each image was examined, and appropriate doses were determined from the calculated IQF to obtain the same image quality for other digital chest imaging systems. The method of determining IQF from C-D phantom analysis was very useful for comparing image quality and determining radiographic techniques. | 10.6009/jjrt.kj00000922532 |
pubmed_942_25985 | OBJECTIVE
To determine the prevalence of HIV, Hepatitis B (HBV) and Hepatitis C (HCV) amongst the health workers of Civil Hospital Karachi (CHK).
MATERIAL AND METHODS
Prospective study. A precoded Proforma was filled out which included questions regarding the knowledge, attitude and practices (KAP) of HIV, HBV and HCV.
SETTING
Departments of a tertiary health care facility at CHK. Antibodies to HIV, HCV and Hepatitis B surface antigen (HBsAg) were done using enzymes linked immunosorbent assay [ELISA].
RESULTS
Uptake of screening was 98% to those offered. The prevalence was 5.6% for antibodies to HCV, 2.4% for HBsAg, while none of those studied had antibodies to HIV.
CONCLUSION
Our results show the prevalence of antibodies to HCV in health workers are 20 folds higher than health workers in the developed countries. Similarly, the prevalence of HBV although not as high as HCV is significant. Seroprevalence of HIV does not exist in this group. We need to ensure better training; regulations regarding preventive and safety measures also need to be enforced (JPMA 52:92; 2002). | pubmed_942_25985 |
pubmed_801_24128 | For over a decade, bisphosphonate administration has evolved and become the cornerstone of the prevention and treatment of fragility fractures. Millions of post-menopausal women have relied on, and continue to depend on, the long-acting, bone density-maintaining pharmaceutical drug to prevent low-energy fractures. In return, we have seen the number of fragility fractures decrease, along with associated costs and emotional benefits. However, with any drug, there are often concerns with side effects and complications, and this unique drug class is seeing one such complication in atypical subtrochanteric femoral fracture, counterproductive to that which it was designed to prevent. This has created concern over long-term bisphosphonate administration and its potential link to these atypical fractures. There is controversial evidence surrounding such a definitive link, and no protocol for managing these fractures. This review offers the latest information regarding this rare but increasingly controversial adverse effect and its potential connection to one of the most successful forms of treatment that is available for the management of fragility fractures. | 10.1302/0301-620X.93B10.26924 |
pubmed_267_9474 | A gas-liquid chromatographic (GLC) method is described for determining 4-chlorophenoxyacetic acid (CPA) residues in mung bean sprouts. The residues were extracted from samples by using ethyl acetate followed by liquid-liquid partition into 5% NaHCO3 solution. After acidification and reextraction with ethyl acetate, CPA was reacted with pentafluorobenzyl bromide (PFB-Br) to form the PFB derivative. The reaction mixture was separated on a silica gel column to remove excess reagent, and the derivative was eluted with a solution of 75% toluene in hexane. GLC separations were performed on a 3% OV-1 column at 230 degrees C. As low as 10 pg CPA could be quantitated, which is equivalent to about 0.05 ppm at residue level, using an electron capture detector. Recoveries of CPA from fortified mung bean sprouts (0.05, 0.20, and 0.50 ppm) ranged from 71 to 107%. The PFB derivative was further identified by gas chromatography-mass spectrometry. | pubmed_267_9474 |
pubmed_795_11638 | A theoretical model is presented, which attempts to account for the evaluation of complex stimuli in terms of their constituent elements that are relevant to the intent of the assessment. The subjective evaluation of a compound stimulus is postulated to be a function of the number, weight and integrity of critical components, or sub-qualities, and their interactions. The model has application to the evaluation of any stimulus complex including works of "art". For illustrative purpose, it will here be applied to the analysis of pictorial works of art. | pubmed_795_11638 |
pubmed_239_4373 | Wetland-estuarine-marine environments are typical oxic/anoxic transition zones and have complex water flow-paths within the zone of mixing where freshwater interacts with ocean water. Little is known about the impact of this interaction on bacterial community structures or the relationship between bacterial community and geochemical factors in such transitional mixing environments. Hence, we investigated the distribution patterns and diversity in bacterial communities in the Yellow River estuary-coastal wetland-Bohai Sea transition zone by analyzing 39 samples from 13 ordered sites. High-throughput sequencing of the 16S rRNA gene revealed significant shifts in diversity and distribution of bacterial community in sediments from the Yellow River estuary to the Bohai Sea. Yellow River sediment was dominated by hydrogen-, nitrogen-, and iron-cycling bacteria, such as Hydrogenophaga, Nitrospira, Pseudomonas, and Thiobacillus. The coastal wetland had a haloduric community associated with different functions, such as Planctomyces, Marinobacter, Halomonas, Salinivibrio, and Salinibacter. The Bohai Sea sediment had a higher relative abundance of Lutimonas, Desulfococcus, Photobacterium, Propionigenium, and Vibrio. Spatial variation in bacterial community was correlated with pH, salinity and sulfate (SO42-) concentration in such coastal environments. The major bacterial taxa were significantly different across the wetland, estuary, and coastal marine ecosystems, indicating substantial spatial heterogeneity among the three ecosystems. Statistical analysis revealed strong links between variation in bacterial community structure and ecosystem type. Our results demonstrate the importance of geographic and geochemical factors in structuring the bacterial community in natural environments. | 10.1002/jobm.201700041 |
pubmed_362_12985 | BACKGROUND
While recent works suggested that overweight/obesity may impair executive function (EF), the overweight/obesity-EF relationship has not been well studied in adolescents. Furthermore, no research has investigated adolescent EF impairments across the weight spectrum (e.g., underweight or thinness, normal, overweight/obesity), especially those with underweight condition, with the moderating effect of negative emotions in the weight-EF association being limitedly investigated. We aimed to determine whether overall and abdominal weight spectrum associated with EF impairments and to identity whether negative emotions moderate the weight-EF link in adolescents.
METHODS
We applied a subsample of the SCHEDULE-A project. Adolescents (11-18 years) were recruited using a multi-stage cluster random sampling approach. We measured the overall and abdominal weight spectrum by body mass index z-score and waist-to-height ratio, respectively. We used the Behavior Rating Inventory of Executive Function (BRIEF) to evaluate adolescent EF in nature setting, and utilized the Depression Anxiety and Stress Scales (DASS-21) to assess three types of negative emotional status (i.e., depression, anxiety, and stress).
RESULTS
Of the 1935 adolescents, 963 (49.8%) were male. We observed that abdominal, not overall, overweight was associated with the Global Executive Composite (GEC) impairment (OR = 1.59, 95% CI 1.07-2.35), particularly for inhibit, emotion control, shift, working memory, and monitor domains. Furthermore, depression moderated the abdominal overweight-GEC association (P = 0.032 for interaction term), especially for emotional control, working memory, and initiate dimensions. Moreover, we also found abdominal thinness was associated with the Metacognition Index problem (OR = 1.33, 95% CI 1.04-1.72), particularly for plan and monitor areas.
CONCLUSIONS
Both abdominal overweight and thinness were associated with adolescent EF, and depression would be a modifiable target to improve EF in adolescents with abdominal overweight. Future longitudinal studies are needed to investigate the causal relationship between abdominal weight spectrum and EF, as well as the underlying mechanisms among adolescents suffering from depression. | 10.1186/s13034-022-00468-9 |
pubmed_630_781 | Being the only sustainable source of organic carbon, biomass is playing an ever-increasingly important role in our energy landscape. The conversion of renewable lignocellulosic biomass into liquid fuels is particularly attractive but extremely challenging due to the inertness and complexity of lignocellulose. Here we describe the direct hydrodeoxygenation of raw woods into liquid alkanes with mass yields up to 28.1 wt% over a multifunctional Pt/NbOPO4 catalyst in cyclohexane. The superior performance of this catalyst allows simultaneous conversion of cellulose, hemicellulose and, more significantly, lignin fractions in the wood sawdust into hexane, pentane and alkylcyclohexanes, respectively. Investigation on the molecular mechanism reveals that a synergistic effect between Pt, NbOx species and acidic sites promotes this highly efficient hydrodeoxygenation of bulk lignocellulose. No chemical pretreatment of the raw woody biomass or separation is required for this one-pot process, which opens a general and energy-efficient route for converting raw lignocellulose into valuable alkanes. | 10.1038/ncomms11162 |
pubmed_1134_3279 | Transarterial chemoembolization (TACE) involves the emulsification of a chemotherapeutic agent in a viscous drug carrier, delivered intra-arterially to liver tumor for maximum effect. TACE reduces arterial inflow, diminishes washout of the chemotherapeutic agent, and decreases systemic exposure. Despite evidence of some clinical success with TACE, a new type of microspheres with drug-eluting capabilities may offer a precisely controlled and sustainable release of the chemotherapeutic agent into the tumor bed. In animal trials tumor necrosis (approaching 100%) was greatest at 7 days, with significantly lower plasma concentrations of doxorubicin than in control animals treated with doxorubicin intra-arterially. Clinically, drug-eluting microspheres loaded with doxorubicin, either at 75 mg/m(2) or at a fixed dose of 150 mg, were used recently and no severe disorders of the hepatic function were observed postprocedure, while a substantial reduction of the fetoprotein levels occurred. An interim analysis of the first 15 patients from the Hong Kong group at 3 months showed an objective response rate of 61.54% and 53.84% according to EASL criteria and RECIST criteria, respectively, and a survival rate of 93.3%. In this paper we present how to use microspheres loaded with doxorubicin and review their clinical value and preliminary performance for treatment of unresectable liver cancer. | 10.1007/s00270-007-9280-6 |
pubmed_764_12424 | In order to clarify cellular responses in dilated renal tubules in the acute and chronic phase of ureteral obstruction, we investigated the expression of proliferating cell nuclear antigen and osteopontin (OPN) in unilateral ureteral obstruction (UUO)-treated rat kidneys. The results showed that renal epithelial cells proliferate in association with tubular dilatation to compensate for the ureteral obstruction in the acute phase of UUO while the proliferative activity decreases in the chronic phase. In the chronic phase, however, the expression of OPN was up-regulated in various tubules but not associated with the tubular dilatation. Taken together with its chemoattractant activity for macrophage, OPN may be involved in the interstitial fibrosis as another compensatory mechanism in the chronic phase of ureteral obstruction. Therefore, these results suggest that two distinct epithelial responses may compensate for the ureteral obstruction in the acute and chronic phase of UUO-treated rat, respectively. | 10.1159/000190298 |
pubmed_103_6173 | The maintenance of the body weight at a stable level is a major determinant in keeping the higher animals and mammals survive. Th e body weight depends on the balance between the energy intake and energy expenditure. Increased food intake over the energy expenditure of prolonged time period results in an obesity. Th e obesity has become an important worldwide health problem, even at low levels. The obesity has an evil effect on the health and is associated with a shorter life expectancy. A complex of central and peripheral physiological signals is involved in the control of the food intake. Centrally, the food intake is controlled by the hypothalamus, the brainstem, and endocannabinoids and peripherally by the satiety and adiposity signals. Comprehension of the signals that control food intake and energy balance may open a new therapeutic approaches directed against the obesity and its associated complications, as is the insulin resistance and others. In conclusion, the present review summarizes the current knowledge about the complex system of the peripheral and central regulatory mechanisms of food intake and their potential therapeutic implications in the treatment of obesity. | pubmed_103_6173 |
pubmed_1006_12612 | The purposes of the present study were to select the optimal conditions for middle latency response (MLR) measuring with a statistical model of orthogonal test, and to determine the normal values of MLR. It showed that stimuli click and logon of different frequencies could be used to evoke MLR. The filter-setting was a significant factor in effecting the measurement of MLR. 30-50Hz or 30-100Hz was the most optimal filter-band. The effects of stimulus polarities on MLR bore no significant difference statistically. In clinical practice, stimulus repetition rate of 11/s was most desirable. We determined that mean thresholds of MLR were approximately 10dBnHL and latencies of wave Po, Na and Pa were approximately 10, 20 and 30ms respectively. The amplitudes of MLR varied greatly. | pubmed_1006_12612 |
pubmed_88_7155 | In March 1988 the Department of Health and Human Services of the US issued a temporary ban on experimental transplants of fetal tissues. The ban was extended on 1 November 1989. See The New York Times, 2 November 1989, Section A, p. 1. | pubmed_88_7155 |
pubmed_6_23472 | Crystallographic point defects (PDs) can dramatically decrease the efficiency of optoelectronic semiconductor devices, many of which are based on quantum well (QW) heterostructures. However, spatially resolving individual nonradiative PDs buried in such QWs has so far not been demonstrated. Here, using high-resolution cathodoluminescence (CL) and a specific sample design, we spatially resolve, image, and analyze nonradiative PDs in InGaN/GaN QWs at the nanoscale. We identify two different types of PDs by their contrasting behavior with temperature and measure their densities from 1014 cm-3 to as high as 1016 cm-3. Our CL images clearly illustrate the interplay between PDs and carrier dynamics in the well: increasing PD concentration severely limits carrier diffusion lengths, while a higher carrier density suppresses the nonradiative behavior of PDs. The results in this study are readily interpreted directly from CL images and represent a significant advancement in nanoscale PD analysis. | 10.1021/acs.nanolett.1c01295 |
pubmed_1047_8099 | Systemic reactions resembling anaphylaxis have occurred after intravenous (IV) iron-dextran administration, a treatment modality that has acquired increased acceptance following the use of erythropoietin for the anemia of patients with chronic renal diseases. Three such patients sustained anaphylactoid reactions immediately after receiving IV test doses of iron-dextran which were their only known exposures. In an effort to determine the mechanism of their reactions, we applied tests for (1) basophil degranulation by iron-dextran, basophil histamine release; (2) a type I anaphylactic reaction, specific IgE antibodies; and (3) an immune complex activation, specific IgG antibodies against iron-dextran. Six other patients with renal diseases served as controls, three of whom had tolerated IV iron-dextran, and three without known exposure. One patient only had any test abnormalities. Her initial positive basophil histamine release and specific IgG antibodies reversed and declined respectively at a 4-month follow-up study. She had developed anaphylaxis, and her studies had been performed at a time after anaphylaxis earlier than the other two. The mechanisms of iron-dextran anaphylaxis may be multiple and not be detectable several months after the incident. Prospective studies will probably be required for a predictive test to be developed. | pubmed_1047_8099 |
pubmed_1003_14109 | Innate immunity is important for early defence against borrelia spirochetes and should play a role in the clinical outcome of the infection. In order to study early cytokine responses, in vitro differentiated dendritic cells (DCs) and whole blood cells from 21 patients with different clinical outcomes of Lyme neuroborreliosis were stimulated with live borrelia spirochetes. The borrelia-induced secretion of interleukin (IL)-4, IL-10, IL-12p70, interferon (IFN)-gamma and tumour necrosis factor (TNF)-alpha in DCs and IL-1beta, IL-6, IL-8, IL-10, IL-12p70, TNF-alpha, regulated upon activation normal T cell expressed and secreted (RANTES), monocyte chemoattractant protein (MCP)-1, macrophage inflammatory protein (MIP)-1alpha, MIP-1beta and eotaxin in whole blood cells was measured by enzyme-linked immunospot (ELISPOT) and multiplex arrays, respectively. We found increased numbers of TNF-alpha-secreting DCs (P = 0.018) in asymptomatic seropositive individuals compared to patients with subacute neuroborreliosis and seronegative controls. Asymptomatic individuals were also found to have elevated levels of IL-12p70 (P = 0.031) in whole blood cell supernatants compared to seronegative controls. These results are in line with previous experiments using cells of the adaptive immune response, indicating that strong T helper type 1 (Th1) proinflammatory responses might be associated with a successful resolution of Lyme disease. | 10.1111/j.1365-2249.2005.02820.x |
pubmed_1040_2068 | Fusaric acid, an inhibitor of dopamine beta-hydroxylase, which converts dopamine to noradrenaline, lowered the blood pressure and induced a subjective improvement in patients with phaeochromocytoma. These effects may be due either to an impairment of catecholamine biosynthesis or to a direct action on the blood vessels. The use of this drug in the treatment of patients with inoperable malignant phaeochromocytoma or neuroblastoma may improve symptoms and prolong survival. | 10.1111/j.1365-2265.1985.tb00142.x |
pubmed_312_19821 | The isolated retina represents an excellent membrane model since it provides a specific electrophysiological response that is easy to quantify. Therefore the authors have tested the effects of B4, C4 and D4 leukotrienes on this model. In the presence of leukotrienes, electrical response generally decreases and survival duration of the isolated retina is generally shortened. No significant difference between the effects of the three tested products has been found. These results are discussed in relation to, on the one hand, the mechanism of intraretinal generation of its electrophysiological signal and, on the other hand, the leukotrienes' role in inflammatory diseases of the retina. | pubmed_312_19821 |
pubmed_386_4882 | BACKGROUND
Hyperuricemia and gout are associated with an increased risk of cardiovascular disease (CVD). It is unknown whether treating hyperuricemia with xanthine oxidase inhibitors (XOIs), including allopurinol and febuxostat, modifies cardiovascular risks.
METHODS
We used US insurance claims data to conduct a cohort study among gout patients, comparing XOI initiators with non-users with hyperuricemia defined as serum uric acid level ≥6.8 mg/dL. We calculated incidence rates of a composite nonfatal cardiovascular outcome that included myocardial infarction, coronary revascularization, stroke, and heart failure. Propensity score (PS)-matched Cox proportional hazards regression compared the risk of composite cardiovascular endpoint in XOI initiators vs those with untreated hyperuricemia, controlling for baseline confounders. In a subgroup of patients with uric acid levels available, PS-matched Cox regression further adjusted for baseline uric acid levels.
RESULTS
There were 24,108 PS-matched pairs with a mean age of 51 years and 88% male. The incidence rate per 1000 person-years for composite CVD was 24.1 (95% confidence interval [CI] 22.6-26.0) in XOI initiators and 21.4 (95% CI, 19.8-23.2) in the untreated hyperuricemia group. The PS-matched hazard ratio for composite CVD was 1.16 (95% CI, 0.99-1.34) in XOI initiators vs those with untreated hyperuricemia. In subgroup analyses, the PS-matched hazard ratio for composite CVD adjusted for serum uric acid levels was 1.10 (95% CI, 0.74-1.64) among XOI initiators.
CONCLUSIONS
Among patients with gout, initiation of XOI was not associated with an increased or decreased cardiovascular risk compared with those with untreated hyperuricemia. Subgroup analyses adjusting for baseline uric acid levels also showed no association between XOI and cardiovascular risk. | pubmed_386_4882 |
pubmed_139_9171 | The epidermal growth factor (EGF) receptor is present in the mouse placenta in both a low- and a high-affinity form having approximate values for Ka of 10(7) M-1 and 10(9) M-1, respectively. No significant difference (P greater than or equal to 0.05) in the number of receptors existed between placental membrane preparations from days 10 and 17, both for the low- and the high-affinity receptor. The number of both high- and low-affinity receptors was significantly lower (P less than 0.05) for day 14 placental membranes than for either day 10 or day 17 placental membranes. Cross-linking of 125I-EGF to placental membranes resulted in the specific labelling of two major receptor forms with approximate molecular weights of 170,000 and 154,000, as determined by sodium dodecyl sulphate-polyacrylamide gel electrophoresis. | 10.1016/s0143-4004(86)80137-0 |
pubmed_157_2709 | AIM
The aim of this study was to identify and assess the degree and clinical course of the main health-related quality-of-life (HRQoL) issues in patients after a distal radius fracture (DRF).
MATERIALS AND METHODS
Patients were eligible if they were between 18-80 years and were within 1-3 days after a non-comminuted DRF. All patients filled out the Polish version of the IOF QLQ, the SF-36 and a demographic questionnaire. Assessment points were set as soon as possible after the fracture, 7 days, 6 weeks, 3 months, and 6 after the fracture. Standard statistical analyses were performed.
RESULTS
During the 16 month recruitment period a total of 71 patients (55 women - 77.5%), with a mean age of 64.1 ± 12.4 years, were included in the study group. All patients suffered from Colles type fractures. Attrition to follow-up was acceptable. At baseline, basing on the IOF QLQ scale scores, DRF patients had the most significant problems with physical function (82.8/100; with 100 representing the worst possible HRQoL), and general health (78.1/100). Basing on SF-36 scale scores patients most significant problems were associated with role limitations due to physical health problems (15.1/100; with 100 representing the best possible HRQoL), and bodily pain (39.5/100).
CONCLUSIONS
Concluding, this study shows that the main issues with which patients with and extra-articular DRF struggle the most are pain of the fractured extremity and physical dysfunction. These symptoms are most pronounced in the early post-injury period, and in the majority of patients steadily decrease over a period of six months. | pubmed_157_2709 |
pubmed_340_21801 | OBJECTIVE
To test the effect of activation of P2X7 receptors on retinal blood velocity in diabetic rabbits.
METHODS
Immunohistochemical analysis was performed on healthy and diabetic rabbit eyes using P2X7 receptor antibodies. Diabetes was induced using alloxan. Retinal blood velocity was measured with the laser speckle circulation analyzer. Visual function was assessed using electroretinography.
RESULTS
Cells in inner retinal layers were positive for anti-P2X7 receptor antibodies in healthy rabbits. The distribution of positive cells extended to outer layers and some small vessels stained in diabetic rabbits. When assayed 24 hours after an intravitreal injection of 150 nmol of benzoylbenzoyl adenosine triphosphate (BzATP), a P2X7 agonist, the retinal blood velocity in healthy rabbits was reduced by approximately 30%; this reduction continued for at least 4 weeks. Only in diabetic rabbits did an injection of 50 nmol of BzATP reduce retinal blood velocity by approximately 30% and the amplitudes of electroretinography a waves, b waves, and oscillatory potentials for at least 4 weeks.
CONCLUSIONS
Soon after the onset of alloxan-induced diabetes, retinal blood velocity and function become more vulnerable to reduction initiated through P2X7 receptors.
CLINICAL RELEVANCE
Our findings support the hypothesis that the retinal circulation disorder accelerated by activation of P2X7 receptors may be involved in the early changes of diabetic retinopathy. | 10.1001/archopht.124.8.1143 |
pubmed_128_14357 | OBJECTIVE
To develop a scale for assessing mindfulness named Srithanya Sati Scale (SSS) in Thai context.
METHODS
Fourteen items were derived with the help from meditation experts. These were then validated by 16 mental health experts followed by analysis of their psychometric properties. A total of 466 subjects were purposively sampled from various sources. The construct validity of the scale was examined by confirmatory factor analysis. The hierarchical model was applied to test whether 3-factor model of SSS could adequately explain overall mindfulness. Test-retest reliability and the internal consistency of each subscale (awareness, acceptance, and self-recollection) were analysed by Pearson's correlation coefficient and Cronbach's alpha, respectively. Srithanya Stress Test was applied to test the discriminant validity of the questionnaire. The Philadelphia Mindfulness Scale was used for testing the concurrent validity.
RESULTS
The 11-item SSS was found to fit across groups of people with different meditation experiences. Two of the components (awareness and self-recollection) explained the overall mindfulness in beginners. The reliability and other psychometric properties of the scale were highly acceptable.
CONCLUSION
The SSS may be a reliable, valid, and acceptable tool for measuring mindfulness in the Thai population. Further studies are warranted in people with more experience in meditation, as well as clinical populations. | pubmed_128_14357 |
pubmed_183_2036 | DNA replication is initiated by recruitment of Cdc18 to origins. During S phase, CDK-dependent destruction of Cdc18 occurs. We show that when DNA replication stalls, Cdc18 persists in a chromatin-bound complex including the checkpoint kinases Rad3 and Rad26. Rad26 directly binds Cdc18 and is required for Rad3 recruitment to chromatin. Depletion of Cdc18 when DNA replication is stalled leads to release of Rad3 and Rad26 from chromatin and entry into an aberrant mitosis even though replication intermediates can still be detected. These findings indicate that Cdc18 plays a pivotal role in checkpoint maintenance by anchoring the Rad3-Rad26 complex to chromatin. Cdc18 persistence during DNA-replication arrest requires the S phase checkpoint that inhibits the S phase CDK. We propose that S phase arrest activates the S phase checkpoint blocking mitosis onset and inhibiting Cdc18 degradation, and that the stabilized Cdc18, in turn, anchors Rad3 to chromatin to ensure long-term checkpoint maintenance. | 10.1016/j.molcel.2007.04.014 |
pubmed_277_68 | BACKGROUND
One hypothesis to explain selective serotonin reuptake inhibitor (SSRI)-induced bruxism states that SSRIs increase extrapyramidal serotonin levels, thereby inhibiting dopaminergic pathways controlling movement. Previous reports have emphasized buspirone's postsynaptic dopaminergic effect as a partial antidote to the suppressed dopamine levels.
CASE REPORTS
Four patients, recently started on treatment with the SSRI sertraline, presented with new-onset complaints attributable to SSRI-induced bruxism. All 4 responded to adjunctive buspirone, a serotonin-1A (5-HT1A) receptor agonist, with relief of bruxism and associated symptoms.
DISCUSSION
We expand the hypothesis put forth in previous reports by proposing that buspirone is not only acting postsynaptically in the extrapyramidal system, but also presynaptically on serotonergic neurons that influence masticatory modulation in the mesocortical tract. Our 4 cases support the concept of buspirone acting as a full agonist at the presynaptic 5-HT1A somatodendritic receptors located on the cell bodies of raphe serotonergic neurons that project to the ventral tegmental area (VTA) of the midbrain. These serotonergic neurons modulate the firing of the mesocortical tract, which itself projects from the VTA to the prefrontal cortex and acts on masticatory muscle activity through inhibiting spontaneous movements such as bruxism. While the literature is confusing and contradictory on definitions of bruxism and etiologies of incompletely understood movement disorders, we believe SSRI-induced bruxism is best conceptualized as a form of akathisia. | 10.4088/jcp.v60n1209 |
pubmed_574_2385 | We report on a series of 33 consecutive cases of antrochoanal polyp (ACP) treated by endoscopic sinus surgery over a five-year period. All but one patient was treated by endoscopic sinus surgery alone. This method of treatment was quite effective for ACPs. These 33 patients represent 22.3% of all nasal polyp patients on whom we operated during the same period. This incidence of ACP is greater than that generally reported in the literature. Some authors have attempted to distinguish ACPs from common nasal polyps primarily on the basis of morphology, histology, and the clinical behavior of the ACPs. In our series, a multivariate analysis, including histopathologic correlation, did not support the notion that ACPs are clearly distinct from common nasal polyps. Some interesting differences between the polyp groups did, however, become evident in our data analysis. Generally, ACPs are not thought to be associated with allergic disease; however, in our series we found the association of allergic disease with ACPs to be statistically significant (Chi-square = 4.575, p < .05). | pubmed_574_2385 |
pubmed_578_15293 | There exists a divide between findings from integrative neuroscience and clinical research focused on mechanisms of psychopathology. Specifically, a clear correspondence does not emerge between clusters of complex clinical symptoms and dysregulated neurobiological systems, with many apparent redundancies. For instance, many mental disorders involve multiple disruptions in putative mechanistic factors (e.g., excessive fear, deficient impulse control), and different disrupted mechanisms appear to play major roles in many disorders. The Research Domain Criteria (RDoC) framework is a heuristic to facilitate the incorporation of behavioral neuroscience in the study of psychopathology. Such integration might be achieved by shifting the central research focus of the field away from clinical description to more squarely examine aberrant mechanisms. RDoC first aims to identify reliable and valid psychological and biological mechanisms and their disruptions, with an eventual goal of understanding how anomalies in these mechanisms drive psychiatric symptoms. This approach will require new methods to ascertain samples, relying on hypothesized psychopathological mechanisms to define experimental groups instead of traditional diagnostic categories. RDoC, by design, uncouples research efforts from clinically familiar categories to focus directly on fundamental mechanisms of psychopathology. RDoC proposes a matrix of domains and levels of analyses and invites the field to test and refine the framework. If RDoC is successful, the domains will ultimately relate to familiar psychopathologies in ways that promote new knowledge regarding etiology and more efficient development of new preventive and treatment interventions. | 10.1037/a0020909 |
pubmed_545_23064 | The complete mitochondrial genome sequence of Deroceras reticulatum has been sequenced and annotated in this study. The mitogenome of D. reticulatum is 14,048 base pairs in length, and contains 13 protein-coding genes (PCGs), 22 transfer RNA genes, and 2 ribosomal RNA genes. The overall base composition is 31.0% A, 12.2% C, 17.7% G, and 39.1% T. Based on phylogenetic analysis using the amino acid sequences of PCGs, D. reticulatum was shown to be closely related to other species of Stylommatophora. The first mitochondrial genome from the Agrolimacidae family provides valuable molecular data for taxonomical identification and further evolutionary studies of terrestrial slugs. | 10.1080/23802359.2017.1318677 |
pubmed_183_22015 | The radiological features of 65 rabbits with suspected renal disease are reviewed. The radiological features included a generalised increase in bone opacity (osteosclerosis), renomegaly, nephroliths, ureteroliths and soft tissue mineralisation. One or more of these changes were present on radiographs of 57 of the 65 rabbits. Renal disease was suspected because of the clinical signs and the presence of kidney stones and/or high blood concentrations of urea and creatinine. Significant renal disease was confirmed in 14 cases that were examined postmortem. Blood urea and creatinine concentrations were measured in 47 cases but not all the rabbits had high levels of both. Blood calcium concentration was high in 33 of the 38 rabbits in which it was measured. Serum phosphate was high in 17 and low in five of 34 rabbits in which it was measured. Hyperphosphataemia was associated with generalised osteosclerosis and aortic calcification. Rabbits with osteosclerosis were thin, depressed and unwilling to move. Thirty-eight of 41 rabbits that were tested were seropositive for antibodies to Encephalitozoon cuniculi. Histological lesions suggestive of E cuniculi infection were found in all 13 cases that were examined postmortem, although the organisms were visible in only one case. | 10.1136/vr.160.23.787 |
pubmed_12_20331 | Colonic polyps are not rare in Brunei Darussalam with an incidence of 13% in 193 colonoscopies performed over the last two years. Majority of the polyps were adenomatous. Incidence was higher in the Malays and had a male preponderance. Commonest age of presentation was above the age of 40 years and the pattern is comparable to the Western pattern. All the polyps were removed by colonoscopic polypectomy. | pubmed_12_20331 |
pubmed_198_13967 | Sixteen chelating agents were examined to determine their relative efficacy as antidotes in acute zinc acetate intoxication in mice after i.p. administration. For a i.p. dose of 0.49 mmol/kg (LD50) of zinc acetate, the i.p. administration of chelating agents at a 2:1 and 5:1 mole ratio resulted in a significant antidotal action for EDTA, DTPA, CDTA, D-penicillamine (D-PA), DMPS and DMSA. EGTA, L-cysteine, triethylentetraamine (TTHA), N-acetylcysteine (NAC), 4,5-dihydroxi-1,3-benzenedisulfonic acid (Tiron), sodium salicylate, glutathione, sodium diethyldithiocarbamate (DDC), 6-mercaptopurine and N-acetyl-D, L-penicillamine (NAPA) were not effective for acute zinc acetate poisoning. The therapeutic indices and therapeutic effectiveness of the most effective chelators were, respectively: EDTA (5.0, 7.0), DTPA (7.3, 13.7), CDTA (8.6, 6.3), D-PA (4.6, 1.9), DMPS (1.3, 1.0), DMSA (3.2, 5.4). DTPA, CDTA, and EDTA appear to be the most effective agents of those tested in offsetting acute zinc intoxication in mice. | 10.1007/BF00364857 |
pubmed_852_3832 | Gene delivery has attracted increasing interest as a highly promising therapeutic method to treat various diseases, including both genetic and acquired disorders. Viral-vectors based gene delivery can achieve higher transduction efficiency and long-term gene expression, but they may be associated with some shortcomings, such as immunogenicity, carcinogenicity, poor target cell specificity, inability to transfer large size genes and high costs. Non-viral approaches show high potential due to advantages of relative safety, ability to transfer large size gene, less toxicity and easiness for preparation etc. However, the clinical application of non-viral methods is still restricted by some limitations including low transfection efficiency and poor transgene expression. In order to improve gene transfer efficacy, a lot of efforts have been made in the past years, and numerous gene carriers and techniques have been developed. In this review, we summarized the features, drawbacks and prospects of existing and emerging non-viral gene delivery methods. | pubmed_852_3832 |
pubmed_605_24039 | BACKGROUND
Salmonella enterica species are enteric pathogens that cause severe diseases ranging from self-limiting gastroenteritis to enteric fever and sepsis in humans. These infectious diseases are still the major cause of morbidity and mortality in low-income countries, especially in children younger than 5 years and immunocompromised adults. Vaccines targeting typhoidal diseases are already marketed, but none protect against non-typhoidal Salmonella. The existence of multiple non-typhoidal Salmonella serotypes as well as emerging antibiotic resistance highlight the need for development of a broad-spectrum protective vaccine. All Salmonella spp. utilize two type III Secretion Systems (T3SS 1 and 2) to initiate infection, allow replication in phagocytic cells and induce systemic disease. T3SS-1, which is essential to invade epithelial cells and cross the barrier, forms an extracellular needle and syringe necessary to inject effector proteins into the host cell. PrgI and SipD form, respectively, the T3SS-1 needle and the tip complex at the top of the needle. Because they are common and highly conserved in all virulent Salmonella spp., they might be ideal candidate antigens for a subunit-based, broad-spectrum vaccine.
PRINCIPAL FINDINGS
We investigated the immunogenicity and protective efficacy of PrgI and SipD administered by subcutaneous, intranasal and oral routes, alone or combined, in a mouse model of Salmonella intestinal challenge. Robust IgG (in all immunization routes) and IgA (in intranasal and oral immunization routes) antibody responses were induced against both proteins, particularly SipD. Mice orally immunized with SipD alone or SipD combined with PrgI were protected against lethal intestinal challenge with Salmonella Typhimurium (100 Lethal Dose 50%) depending on antigen, route and adjuvant.
CONCLUSIONS AND SIGNIFICANCE
Salmonella T3SS SipD is a promising antigen for the development of a protective Salmonella vaccine, and could be developed for vaccination in tropical endemic areas to control infant mortality. | 10.1371/journal.pntd.0005207 |
pubmed_245_11281 | BACKGROUND
A wide array of miscellaneous agents is being studied for the treatment of atopic dermatitis (AD), including targeted topical, oral systemic, and biologic agents.
OBJECTIVE
To review the known efficacy and safety to date for such agents being studied for the treatment of AD.
METHODS
A nonsystematic review of the literature was performed. PubMed and ClinicalTrials.gov were searched for studies assessing agents not described previously for the treatment of AD. Randomized controlled trials were primarily sought, but other study types were also included if they contained pertinent data. Agents are presented by mechanism of action, with analysis of mechanism of action and data regarding efficacy and safety in patients with AD.
RESULTS
Data regarding the following agents are presented: omiganan (an antimicrobial peptide), tapinarof (a nonsteroidal anti-inflammatory agent), PR022 (hypochlorous acid), asimadoline (a κ-opioid agonist), DS107 (dihomo-γ-linolenic acid), ZPL-389 (a histamine H4 receptor antagonist), secukinumab (an interleukin 17A inhibitor), and fezakinumab (interleukin 22 inhibitor).
LIMITATIONS
Limited clinical data exist for many of the described agents.
CONCLUSIONS
As recent research has improved our understanding of AD pathogenesis, various agents with unique mechanisms of action have been studied for the treatment of AD. Many of these hold great therapeutic promise for AD, and continued research and development is warranted. | 10.1016/j.jaad.2017.12.024 |
pubmed_674_5269 | Heritable microbes are abundant in nature and influential to their hosts and the communities in which they reside. However, drivers of variability in the prevalence of heritable symbionts and their rates of transmission are poorly resolved, particularly across host populations experiencing variable biotic and abiotic environments. To fill these gaps, we surveyed 25 populations of two native grasses (Elymus virginicus and Elymus canadensis) across the southern Great Plains (USA). Both grass species host heritable endophytic fungi (genus Epichloё) and can hybridize where their ranges overlap. From a subset of hosts, we characterized endophyte genotype using genetic loci that link to bioactive alkaloid production. First, we found mean vertical transmission rates and population-level prevalence were positively correlated, specifically for E. virginicus. However, both endophyte prevalence and transmission varied substantially across populations and did not strongly correlate with abiotic variables, with one exception: endophyte prevalence decreased as drought stress decreased for E. virginicus hosts. Second, we evaluated the potential influence of biotic factors and found that, after accounting for climate, endophyte genotype explained significant variation in symbiont inheritance. We also contrasted populations where host species co-occurred in sympatry vs. allopatry. Sympatry could potentially increase interspecific hybridization, but this variable did not associate with patterns of symbiont prevalence or transmission success. Our results reveal substantial variability in symbiont prevalence and transmission across host populations and identify symbiont genotype, and to a lesser extent, the abiotic environment as sources of this variation. | 10.1007/s00248-017-0964-4 |
pubmed_213_4502 | Allergen exposure may precipitate acute bronchoconstriction and increase bronchial reactivity. We have investigated whether passive sensitisation of human airway per se or short-term exposure to mediators released by specific antigen exposure produces an alteration in in vitro smooth muscle sensitivity to histamine. Exposure to allergen produced smooth muscle contraction in sensitised tissue, but subsequent smooth muscle sensitivity to histamine was not altered. We conclude that neither passive sensitisation nor short-term exposure to mast cell mediators alters in vitro smooth muscle sensitivity to histamine. | 10.1016/0952-0600(89)90031-8 |
pubmed_1026_5543 | Mutations of Ubiquilin 2 (UBQLN2) or TANK-binding kinase 1 (TBK1) are associated with amyotrophic lateral sclerosis and frontotemporal degeneration (ALS/FTD). However, the mechanisms whereby UBQLN2 or TBK1 mutations lead to ALS and FTD remain unclear. Here, we explored the effect of UBQLN2 on TBK1 in HEK-293T cells or in CRISPR-Cas9-mediated IRF3 and IRF7 knockout (KO) cells. We found an interaction between TBK1 and UBQLN2, which was affected by ALS/FTD-linked mutations in TBK1 or UBQLN2. Co-expression of UBQLN2 with TBK1 elevated the protein level of TBK1 as well as the phosphorylation of TBK1 and IRF3 in a UBQLN2 dose-dependent manner, and this phosphorylation was reduced by mutant UBQLN2. In addition, the cellular production of IFN1 and related pro-inflammatory cytokines was substantially elevated when UBQLN2 and TBK1 were co-expressed, which was also decreased by mutant UBQLN2. Functional assay revealed that mutant UBQLN2 significantly reduced the binding affinity of TBK1 for its partners, including IRF3, (SQSTM1)/p62 and optineurin (OPTN). Moreover, complete loss of IRF3 abolished the induction of IFN1 and related pro-inflammatory cytokines enhanced by UBQLN2 in HEK-293T cells, whereas no significant change in IRF7 knockout cells was observed. Thus, our findings suggest that UBQLN2 promotes IRF3 phosphorylation via TBK1, leading to enhanced IFN1 induction, and also imply that the dysregulated TBK1-IRF3 pathway may play a role in UBQLN2-related neurodegeneration. | 10.3390/cells9051205 |
pubmed_244_18215 | OBJECTIVE
Human genome-wide association studies and animal models suggest a role for TGFB2 in contributing to the corneal thickness phenotype. No specific mutations, however, have been reported in this gene that affect corneal thickness. We sought to determine if haploinsufficiency of TGFB2 in humans associated with Loeys-Dietz syndrome type 4 is associated with corneal thinning.
DESIGN
Observational cohort study of families with Loeys-Dietz syndrome type 4, caused specifically by TGFB2 mutations, in a tertiary care setting.
PARTICIPANTS
Three probands with pathogenic mutations in TGFB2 and family members underwent comprehensive ophthalmic examination.
METHODS
Clinical assessment included Scheimpflug imaging, specular microscopy, and slit-lamp biomicroscopy. We measured visual acuity, axial length, refractive error, and central corneal thickness.
RESULTS
Clinical evaluation of 2 probands identified corneal thinning and cornea guttata, despite a young age and distinct mutations in TGFB2 (c.905G>A, p.Arg302His; c.988C>A, p.Arg330Ser). In the third family, corneal thinning co-segregated with a TGFB2 mutation (c.1103G>A, p.Gly368Glu), although without apparent guttae.
CONCLUSIONS
In this series, participants with TGFB2 mutations associated with Loeys-Dietz syndrome type 4 demonstrated decreased corneal thickness, and in 2 cases with splice site mutations, also demonstrated cornea guttata. The data demonstrate the importance of considering distinct phenotype-genotype correlations within this condition. | 10.1016/j.jcjo.2020.03.007 |
pubmed_1077_2551 | Cell apoptosis can cause hippocampal neuronal loss after epileptic seizures. Hypoxia inducible factor (HIF)-1α is an important factor mediating apoptosis after brain injuries, such as cerebral ischemia and traumatic brain injures, but little research has been done on its role in the lithium chloride-pilocarpine induced epileptic model. Here, we used a rat model of pilocarpine-induced status epilepticus (SE) to investigate HIF-1α expression and apoptosis in the hippocampus, and to explore their relationship during epileptogenesis. 120 male Sprague Dawley (SD) rats were treated with lithium chloride-pilocarpine injections and divided into an experimental group (administered by MK-801) and a positive control group (administered by saline). Then the HIF-1α expression and hippocampal apoptosis were investigated by histological confirmation and western blotting at 24h, 3d, 7d and 14d, respectively. The results showed that the administration of MK-801 significantly reduced (P<0.05) HIF-1α expression and hippocampal apoptosis during epileptogenesis in comparison with the positive control. Moreover, the expression of HIF-1α and hippocampal apoptosis presented significant time-dependent changes (P<0.01) within 2 weeks, and their positive correlation (P<0.05) analyzed by Pearson׳s correlation analysis. Meanwhile, the HIF-1α immunostained cells were distributed in accord with TUNEL immunostained cells and Caspase-3 immunopositive cells in the hippocampus. These results indicate that the HIF-1α expression is associated with hippocampal apoptosis, and suggest that HIF-1α is an important factor during epileptogenesis. | pubmed_1077_2551 |
pubmed_463_12784 | We investigated whether THI-28 [1-4-(hydroxyphenylethyl)-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline] inhibits release of high mobility group box 1 (HMGB1), a late phase cytokine of sepsis, in lipopolysaccharide (LPS)-stimulated RAW264.7 cells through heme oxygenase (HO)-1 induction so that it shows beneficial effects in the cecal ligation and puncture (CLP)-induced septic mouse model. Silencing of target genes (HO-1, Nrf-2) or pharmacological signal inhibitors was exploited to investigate the HO-1 induction by THI-28. The dependency of HO-1 by THI-28 on survival rate and circulating HMGB1 level was tested in CLP-induced septic mice. Results showed that a time- and concentration-dependent HO-1 induction by THI-28 was significantly reduced by transfection with siNrf2 RNA. The reduction of iNOS/NO and HMGB1 expression by THI-28 was significantly reversed by silencing HO-1 RNA or treatment with SB203580, a p38 MAPK inhibitor, or LY294002, a PI3K inhibitor in LPS-activated cells. Decreasing p-IκBα by THI-28 resulted in inhibition of NF-κB activity which was reversed by silencing HO-1 RNA in LPS-activated cells. Most importantly, increased survival and reduction of liver and kidney injury and circulating HMGB1 levels by THI-28 in CLP-mice were reversed by ZnPPIX, HO-1 inhibitor. Taken together, these findings suggest that the novel compound THI-28 induces the expression of HO-1 by activating the PI3K and p38 MAPK pathways and suppressed HMGB1 and iNOS production in LPS-treated macrophages and septic mice, which may be useful in treating organ injury due to sepsis. | pubmed_463_12784 |
pubmed_1004_7253 | It has been demonstrated that the dilution of samples prior to the carboxymethylcellulase and xylanase assays causes serious discrepancies in the numerical values obtained for the enzyme activities. Even when the sample is assayed with the identical procedure, one could obtain different numerical values of the enzyme activity U depending on how much this sample has been diluted before the enzyme assay. Two crude commercial cellulase samples of Aspergillus niger and Trichoderma viride as well as the culture filtrate of our newly isolated acidophilic fungus have been used for the demonstration. An empirical method for reporting the cellulolytic activity by taking into account this dilution effect is proposed. | 10.1002/bit.260260825 |
pubmed_187_4518 | Malignant pheochromocytomas are rare. Although 5-year survival is less than 50%, the prognosis varies. Some patients, even those with extensive metastases, have been followed up for many years. If the tumor tissue's uptake is adequate (> 5 Gy/100 mCi) the therapeutic use of 131I-meta-iodobenzylguanidin (131I-MIBG) is at present the therapy of first choice. The use of cytostatic chemotherapy should be limited to patients with rapidly progressive disease. | pubmed_187_4518 |
pubmed_1048_8212 | A novel tLyP-1-HA-PTX conjugate is designed for combining the solubilization capacity of Paclitaxel (PTX) and tumor tissue targeting - penetration effect of hyaluronic acid (HA) as well as cell penetration peptide (tLyP-1). In addition, through modifying by tLyP-1, the anticancer scope of tLyP-1-HA-PTX conjugate was expanded from tumor cells expressing CD44 receptors to those of expressing NRP1 receptors. In vitro antitumor ability of tLyP-1-HA-PTX conjugate and cellular uptake tests were conducted to testify the tumor-targeting behavior of the conjugates. The results showed that both HA-PTX and tLyP-1-HA-PTX conjugates gained better solubility, better stability and specific tumor sites ability and showed high safety in vitro cytotoxicity tests. The tLyP-1-HA-PTX conjugate was especially endowed with efficient cell-penetrating and tumor NRP1 receptor targeting ability and compensate for the decreasing of uptake caused by suppression of CD44 receptor, which is more significant when NRP1 receptor is highly expressed. | 10.1016/j.carbpol.2016.08.100 |
pubmed_878_3285 | This paper presents the activities and publications of Organisation for Economic Co-operation and Developments (OECD's) Working Group on Harmonisation of Regulatory Oversight in Biotechnology and the Task Force for the Safety of Novel Foods and Feeds. The main outputs of the work are the Series of "consensus documents" of the respective groups. These documents compile information which is intended to be used by those involved in the business of risk/safety assessment. These documents are one means of ensuring the transportability of data amongst authorities. An increasing trend in both the Working Group and Task Force is to consider crop species which are relevant to tropical regions and therefore to countries that are not necessarily members of the OECD. For example, the Working Group has recently published a consensus document on bananas and plantains while the Task Force has published a document on cassava. This trend towards crops of greater interest in the tropics is likely to continue into the future. | 10.1007/s11248-013-9766-8 |
pubmed_732_17283 | The development of adrenergic (indicated by catecholamine fluorescence), acetylcholine-sterase-positive (possibly cholinergic), non-adrenergic, non-cholinergic (indicated by quinacrine fluorescence) nerves and small intensely fluorescent (SIF) cells in the rabbit urinary bladder was examined in foetal (from 23 days of gestation), newborn and adult animals. Acetylcholinesterase-positive nerve fibres and ganglion cells and quinacrine-positive ganglion cells were both present on day 23 of gestation, while quinacrine-positive varicose nerve fibres were first seen on day 24. At foetal age 26 days, 25-38 ganglia containing quinacrine-positive cells were seen in whole-mount preparations of detrusor muscle of the bladder. Each ganglion contained 30-40 quinacrine-positive cells (diameter 20-40 μm). In contrast, only 5-12 ganglia contained acetylcholinesterase-positive nerve cell bodies at the same foetal age with only 3-20 cells in each ganglion; these figures remained at about the same level from foetal age 23 days to maturity. No catecholamine-containing nerve cell bodies were seen at any foetal age or in the adult. Adrenergic nerve fibres were not detected until day 28 of gestation, although small intensely fluorescent cells were first observed on day 26 of gestation. In the adult bladder there was a reduction of approximately 25-35% in the number of quinacrine-positive nerve cell bodies within the ganglia when compared with the ganglia in 1-day-old bladders and an increase in nerve fibre density of about 50% when compared with bladders of earlier ages. A reduction of approximately 90% in small intensely fluorescent cells and a 2-fold increase of adrenergic nerves was also characteristic of the adult bladder, although no changes were observed in the density of the acetylcholinesterase-positive cell bodies and nerve fibres. It is concluded that catecholamine-containing, acetylcholinesterase-positive and non-adrenergic, non-cholinergic nerves follow very different developmental patterns in the bladder. | 10.1016/0736-5748(85)90023-1 |
pubmed_926_17607 | We investigate the transport properties of a junction consisting of an electron-hole bilayer in contact with normal and superconducting leads. The electron-hole bilayer is considered as a semimetal with two electronic bands. We assume that in the region between the contacts the system hosts an exciton condensate described by a BCS-like model with a gap Γ in the quasiparticle density of states. We first discuss how the subgap electronic transport through the junction is mainly governed by the interplay between two kinds of reflection processes at the interfaces: the standard Andreev reflection at the interface between the superconductor and the exciton condensate, and a coherent crossed reflection at the semimetal-exciton-condensate interface that converts electrons from one layer into the other. We show that the differential conductance of the junction shows a minimum at voltages of the order of Γ/e. Such a minimum can be seen as a direct hallmark of the existence of the gapped excitonic state. | 10.1103/PhysRevLett.119.067001 |
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