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pubmed_663_13683
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Bacterial products (e.g., LPS) are viewed as critical stimuli in inflammation-associated cancer. Cyclooxygenase 2 (COX-2), a major effector of LPS, and EGFR, are key to carcinogenesis, notably in the hepatobiliary tract. In this study, we tested the hypothesis that LPS can initiate an interaction between the epidermal growth factor receptor (EGFR) and COX-2 pathways. We examined the effect of LPS in biliary carcinoma cells that displayed constitutive COX-2 expression and PGE(2) production and in normal human biliary epithelial cells in which COX-2/PGE(2) expression was virtually absent. LPS induced early phosphorylation of EGFR and ERK1/2 in both types of cells, which reached maximum levels within 30 min (first phase). However, only the carcinoma cells showed a second significant rise in both EGFR and ERK phosphorylation 6 h after exposure to LPS (second phase). Inhibition of COX-2/PGE(2) production prevented the second, but not the first, phase of EGFR and ERK1/2 phosphorylation, implicating COX-2/PGE(2) in the second phase of phosphorylation. LPS induced COX-2-derived PGE2 production at 4 h, which was before the rise in the second phosphorylation that occurred at 6 h. Exogenous PGE(2) also caused EGFR activation via a signaling pathway involving TACE-dependent TGF-alpha release. Inhibition of the second phase of EGFR phosphorylation with EGFR or COX-2 inhibitor prevented LPS-induced cell invasion in vitro, demonstrating the biological importance of this COX-2 feedback signaling in cancer cells. We conclude that LPS triggers a positive feedback loop involving COX-2/PGE(2) in biliary carcinoma cells and that this second phase of EGFR phosphorylation is implicated in cell invasion by LPS.
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10.4049/jimmunol.0801768
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pubmed_984_438
|
Maintaining an appropriate balance between subsets of CD4(+) Th and T regulatory cells (Tregs) is critical to maintain immune homeostasis and prevent autoimmunity. Through a common requirement for TGF-beta, the development of peripherally induced Tregs is intimately linked to that of Th17 cells, with the resulting lineages depending on the presence of proinflammatory cytokines such as IL-6. Currently very little is known about the molecular signaling pathways that control the development of Tregs vs Th17 cells. Reduced activity of the PI3K pathway is required for TGF-beta-mediated induction of Foxp3 expression and the suppressive activity of Tregs. To investigate how negative regulators of the PI3K pathway impact Treg development, we investigated whether SHIP, a lipid phosphatase that regulates PI3K activity, also plays a role in the development and function of Tregs. SHIP-deficient Tregs maintained suppressive capacity in vitro and in a T cell transfer model of colitis. Surprisingly, SHIP-deficient Th cells were significantly less able to cause colitis than were wild-type Th cells due to a profound deficiency in Th17 cell differentiation, both in vitro and in vivo. The inability of SHIP-deficient T cells to develop into Th17 cells was accompanied by decreased IL-6-stimulated phosphorylation of STAT3 and an increased capacity to differentiate into Treg cells under the influence of TGF-beta and retinoic acid. These data indicate that SHIP is essential for normal Th17 cell development and that this lipid phosphatase plays a key role in the reciprocal regulation of Tregs and Th17 cells.
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10.4049/jimmunol.0803749
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pubmed_648_3304
|
Studies on the effects of transcriptional memory on clone reprogramming in mammals are limited. In the present study, we observed higher levels of active histone H3 lysine 4 trimethylation (H3K4me3 and 5-hydroxymethylcytosine) and repressive (5-methylcytosine) epigenetic modifications in bovine early cloned embryos than in in vitro fertilized embryos. We hypothesized that aberrant epigenetic modification may result in transcriptional disorders in bovine somatic cell nuclear transfer (SCNT) embryos. RNA sequencing results confirmed that both abnormal transcriptional silencing and transcriptional activation are involved in bovine SCNT reprogramming. The cloned embryos exhibited excessive transcription in RNA processing- and translation-related genes as well as transcriptional defects in reproduction-related genes whose transcriptional profiles were similar to those in donor cells. These results demonstrated the existence of active and silent memory genes inherited from donor cells in early bovine SCNT embryos. Further, H3K4me3-specific demethylase 5B (KDM5B) mRNA was injected into the reconstructed embryos to reduce the increased H3K4me3 modification. KDM5B overexpression not only reduced the transcriptional level of active memory genes, but also promoted the expression of silent memory genes; in particular, it rescued the expression of multiple development-related genes. These results showed that transcriptional memory acts as a reprogramming barrier and KDM5B improves SCNT reprogramming via bidirectional regulation effects on transcriptional memory genes in bovines.
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10.1096/fj.201900578RR
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pubmed_1032_14260
|
Blast, caused by Pyricularia grisea (teleomorph: Magnaporthe grisea), is the most devastating disease of finger millet affecting production, utilization, and trade in Africa and Southeast Asia. An attempt was made to select a set of putative host differentials that can be used to determine virulence diversity in finger-millet-infecting populations of M. grisea. Thus, a differential set comprising eight germplasm accessions selected from finger millet core collection (IE 2911, IE 2957, IE 3392, IE 4497, IE 5091, IE 6240, IE 6337, and IE 7079) and a resistant ('GPU 28') and a susceptible ('VR 708') variety was developed. This differential set was used to study pathogenic variation in 25 isolates of M. grisea collected from Karnataka, Telangana, and Andhra Pradesh states in India. Based on the reaction (virulent = score ≥4 and avirulent = score ≤3 on a 1-to-9 scale) on host differentials, nine pathotypes were identified among 25 M. grisea isolates. Pathotype 9, represented by isolate Pg23 from Vizianagaram, was the most virulent because it could infect all of the host differentials except GPU 28. This study will be helpful in devising strategies for monitoring virulence change in M. grisea populations, and for identification of blast resistance in finger millet for use in disease resistance breeding programs.
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10.1094/PDIS-10-14-1089-RE
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pubmed_484_15342
|
Common variable immunodeficiency (CVID) is a primary immunodeficiency characterized by hypogammaglobulinemia. Leptin has been implicated as an antiapoptotic compound as well as a stimulant of the immune response. Leptin administration is capable of reversing the immune deficiency that occurs upon starvation. We investigated a possible role for leptin in CVID; a condition associated with lowered plasma leptin levels. Thirty-eight patients were studied. Addition of leptin to the tissue culture media of PBMC from CVID patients increased the proliferative response of lymphocytes to mitogens and decreased activation-induced apoptosis of these cells. IL-2 and specially IL-4 production also increased significantly upon addition of leptin to the PBMC cultures. Our results suggest that leptin may be involved in some of the cellular defects observed in CVID and indicate a novel therapeutic strategy to improve immune function in these patients.
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10.1016/j.clim.2004.09.002
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pubmed_788_21728
|
Cholesterol-dependent cytolysins (CDCs), a large family of bacterial toxins, are secreted as water-soluble monomers and yet are capable of generating oligomeric pores in membranes. Previous work has demonstrated that large scale structural rearrangements occur during this transition but the detailed mechanism by which these changes take place remains a puzzle. Despite evidence of structural and functional couplings between domains 3 and 4, the crystal structure of the CDC, perfringolysin O (PFO), shows the two domains do not make direct contact. Here, we present crystal structures of PFO that demonstrate movements of domain 4 are sufficient to trigger conformational changes that are transmitted through the molecule to the distant domain 3. These coupled movements result in a loss of many contacts between domain 3 and rest of the molecule that would eventually lead to the exposure of transmembrane regions in preparation for membrane insertion. The structures reveal a detailed molecular pathway that may be the basis for the allosteric transition that occurs on initial membrane binding leading to the exposure of membrane-spanning regions in a domain distant from the initial site of interaction.
|
10.1016/j.jmb.2007.01.042
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pubmed_1086_6717
|
To extend the shelf life of freshly harvested vegetables and cut flowers, a maize homeobox gene Knotted1 (kn1) was placed under the control of a wound-inducible promoter win3.12 from hybrid poplar (Populus trichocarpa x P. deltoides) and introduced into tobacco plants (Nicotiana tabacum cv. Xanthi). Transgenic win3.12::kn1 plants were morphologically normal. A leaf-detachment assay demonstrated that senescence in win3.12::kn1 leaves could be delayed by at least 2 weeks compared with wild type leaves. Furthermore, all leaves of win3.12::kn1 shoots remained green and healthy 3 weeks after excision and incubation in water, while older leaves of control shoots senesced under the same conditions. Additionally, a number of adventitious roots produced at the cut ends of wild type shoots after a 3-week incubation, but much a less number of adventitious roots appeared in win3.12::kn1 shoots. The delay in senescence was also confirmed by a higher total chlorophyll (a + b) content in win3.12::kn1 leaves relative to that of the control plants. RT-PCR analysis showed that the kn1 transcript was detected in win3.12::kn1 leaves with wounding treatment, but otherwise was not observed in leaves of wild type and unwounded transgenic plants. The results presented here indicate that expression of kn1 gene driven by the wound-inducible promoter win3.12 is potentially useful to delay senescence of vegetable crops and commercial horticulture after harvest.
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10.1007/s00299-006-0178-6
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pubmed_806_9806
|
We have re-investigated an unusual cardiac specimen with juxtaposition of the atrial appendages. The original description dates to 1962, when the autopsy was performed at the Children's Memorial Hospital in Chicago, now Ann & Robert H. Lurie Children's Hospital of Chicago. The heart was subsequently stored in the Farouk S. Idriss Cardiac Registry at the same institution. The specimen shows usual atrial arrangement, but with the morphologically left appendage juxtaposed in a rightward manner, passing behind the heart rather than through the transverse sinus so as to reach its location inferior to the morphologically right appendage. The heart also demonstrated an inter-atrial communication between the cavities of the juxtaposed left appendage and the morphologically right atrium. We provide a detailed description of the morphology, and provide images of this lesion, which to the best of our knowledge has not previously been described.
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10.1017/S1047951115000165
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pubmed_1141_13052
|
We studied kinetics in the epiphyseal cartilage of the brachymorphic (bm/bm) mouse, combining morphometry and labeling with halogenated nucleotides. The defective synthesis of the sulfate donor PAPS in these homozygous mutants is evident in tissues with a large production of glycosaminoglycans; these compounds become undersulfated. Compared with their heterozygous siblings, the longitudinal growth of the mutant mice was reduced by two-thirds. This was mainly associated with (1) reduced height of the proliferating zone, (2) a substantial number of G0 cells in this zone, and (3) reduced hypertrophy which, in turn, may be related to premature mineralization and prevention of normal expansion of cells. No significant effects on cell-cycle parameters were detected, such as S-phase time or cell-cycle time, and the rate at which each cell increased the matrix volume seemed normal. An effect on matrix mineralization may be related to known changes in the structure of matrix PGs, whereas the effect on proliferation may be related to other factors. Candidates for such other effects of undersulfation are the cell surface PGs, which are important for binding of growth factors.
|
10.1007/s002230010073
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pubmed_147_13485
|
Papillary fibroelastoma of the aortic valve is an uncommon benign tumor of the heart that can present with embolic events. We report a case of 54-year-old lady with exertional chest pain and prior history of ST segment elevation myocardial infarction who was subsequently found to have a fibroelastoma of the aortic valve. The absence of angiographically significant coronary artery disease and resolution of anginal symptoms post-surgery in our patient points to the possibility of fibroelastoma causing these anginal symptoms. Although uncommon, fibroelastoma are being recognized more frequently with the help of transesophageal echocardiography. Hence, in the absence of significant coronary artery disease, we emphasize the importance of consideration of papillary fibroelastoma of the aortic valve as a cause of angina. We also discuss the key aspects of the fibroelastoma including presentation, diagnostic modalities and treatment options.
|
10.4330/wjc.v5.i4.102
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pubmed_694_5747
|
The application of negative expiratory pressure (NEP) to the airway opening during forced expiratory maneuvers has recently been described as a noninvasive method to assess whether flow limitation is achieved in adults. This methodology has great potential for extending the measurement of forced expiratory maneuvers to young children who may not produce maximal efforts as reproducibly as adults. We used NEP to assess flow limitation in 10 children between 3 and 5 yr of age. NEP was well tolerated by all subjects. With the application of NEP, there was not a step increase in flow, a finding consistent with flow limitation for the subjects. In addition to visual inspection, we proposed a method to quantify the change in flow during a short NEP. The flow-volume curves obtained with and without NEP were visually the same, other than the flow transients produced by NEP. The calculated values of FVC and FEF25-75 were not significantly different when measured from flow- volume curves with and without NEP. There was a statistically significant increase in FEV1 with NEP; however, the group mean increase in FEV1 was less than 2%. We conclude that NEP may be a useful technique to determine whether flow limitation has been achieved in young children performing forced expiratory maneuvers.
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10.1164/ajrccm.159.3.9803001
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pubmed_748_11426
|
To explore the biological effects of light on trabecular cells, cultured bovine trabecular cells were exposed to visible light of different wavelength with different energy. Cellular morphology, structure, proliferation, and phagocytosis were observed. The cells showed no remarkable changes when the energy was low. When the exposure energy reached 1.12 mW/cm2, the cytoplasm showed a rough appearance, and cell proliferation and phagocytosis decreased. This phototoxicity was strong with white light (compound chromatic light), moderate with violet light or yellow light, and mild with red light.
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10.1007/BF02885423
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pubmed_1026_5489
|
The excitatory neurotransmitter glutamate has been implicated in experience-dependent neuroplasticity and drug-seeking behaviors. Type 5 metabotropic glutamate (mGlu5) receptors might be particularly important. They are critically involved in synaptic plasticity and their availability has been reported to be lower in people with alcohol, tobacco, and cocaine use disorders. Since these reductions could reflect effects of drug use or pre-existing traits, we used positron emission tomography to measure mGlu5 receptor availability in young adults at elevated risk for addictions. Fifty-nine participants (age 18.5 ± 0.6) were recruited from a longitudinal study that has followed them since birth. Based on externalizing traits that predict future substance use problems, half were at low risk, half were at high risk. Cannabis use histories varied markedly and participants were divided into three subgroups: zero, low, and high use. Compared to low risk volunteers, those at elevated risk had lower [11C]ABP688 binding potential (BPND) values in the striatum, amygdala, insula, and orbitofrontal cortex (OFC). Cannabis use by risk group interactions were observed in the striatum and OFC. In these regions, low [11C]ABP688 BPND values were only seen in the high risk group that used high quantities of cannabis. When these high risk, high cannabis use individuals were compared to all other participants, [11C]ABP688 BPND values were lower in the striatum, OFC, and insula. Together, these results provide evidence that mGlu5 receptor availability is low in youth at elevated risk for addictions, particularly those who frequently use cannabis.
|
10.1038/s41386-020-0708-x
|
pubmed_470_21006
|
BACKGROUND
Cardiovascular morbidity is a major burden in patients with type 2 diabetes. In the Steno-2 Study, we compared the effect of a targeted, intensified, multifactorial intervention with that of conventional treatment on modifiable risk factors for cardiovascular disease in patients with type 2 diabetes and microalbuminuria.
METHODS
The primary end point of this open, parallel trial was a composite of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, revascularization, and amputation. Eighty patients were randomly assigned to receive conventional treatment in accordance with national guidelines and 80 to receive intensive treatment, with a stepwise implementation of behavior modification and pharmacologic therapy that targeted hyperglycemia, hypertension, dyslipidemia, and microalbuminuria, along with secondary prevention of cardiovascular disease with aspirin.
RESULTS
The mean age of the patients was 55.1 years, and the mean follow-up was 7.8 years. The decline in glycosylated hemoglobin values, systolic and diastolic blood pressure, serum cholesterol and triglyceride levels measured after an overnight fast, and urinary albumin excretion rate were all significantly greater in the intensive-therapy group than in the conventional-therapy group. Patients receiving intensive therapy also had a significantly lower risk of cardiovascular disease (hazard ratio, 0.47; 95 percent confidence interval, 0.24 to 0.73), nephropathy (hazard ratio, 0.39; 95 percent confidence interval, 0.17 to 0.87), retinopathy (hazard ratio, 0.42; 95 percent confidence interval, 0.21 to 0.86), and autonomic neuropathy (hazard ratio, 0.37; 95 percent confidence interval, 0.18 to 0.79).
CONCLUSIONS
A target-driven, long-term, intensified intervention aimed at multiple risk factors in patients with type 2 diabetes and microalbuminuria reduces the risk of cardiovascular and microvascular events by about 50 percent.
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10.1056/NEJMoa021778
|
pubmed_647_2665
|
PURPOSE
Laparoscopic renal and adrenal surgery is an accepted standard of care. This can be accomplished by a transperitoneal or retroperitoneal approach. In patients with extensive prior intra-abdominal surgery with or without radiation the retroperitoneal laparoscopic approach may avoid bowel adhesions and potential operative complications. We compared clinical outcomes of the laparoscopic retroperitoneal approach in patients with prior open abdominal surgery with or without radiation to outcomes in those with no surgical history.
MATERIALS AND METHODS
We evaluated clinical and functional parameters in 78 consecutive patients undergoing retroperitoneoscopic renal or adrenal surgery performed by a single surgeon in a 36-month period, including radical nephrectomy with or without ureterectomy in 50, nerve sparing surgery in 8, ablation in 16 and adrenalectomy in 4. All transperitoneal procedures during the same period were excluded from analysis. Patients were divided into 48 who underwent prior abdominal surgery with or without radiation (group 1) and 30 who did not (group 2). Prior abdominal surgeries in group 1 patients were open and they were major in 42 and/or minor in 39. An additional 6 patients in group 1 received prior abdominal radiation overlapping the planned surgical field.
RESULTS
No statistically significant differences were noted between the groups in any parameter assessed, including operative time, blood loss, time to first oral intake, hospital stay or the complication rate (p >0.05). There were no enterotomies in either group. There were no open conversions in group 1, while there were 2 in group 2 (renal vein injury and splenorrhaphy secondary to lymphoma, respectively). Pathological findings showed malignancy in 57 cases (renal cell carcinoma, transitional cell carcinoma, carcinoid disease and metastases) and benign disease in 21 (oncocytoma, adenoma, pyelonephritis and complex cysts). All margins were negative except in 1 group patient with carcinoma in situ at the bladder cuff margin.
CONCLUSIONS
The retroperitoneoscopic approach to the kidney and adrenal glands can be used in patients with extensive prior open abdominal surgery and/or radiation without significant increases in morbidity or convalescence.
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10.1097/01.ju.0000165654.34635.ad
|
pubmed_1033_17787
|
This article reports on an audit of clinical supervision in one primary care trust (PCT). Data were collected by telephone interviews with 44 respondents from a range of professions occupying different clinical and managerial grades in the organization. Clinical supervision was varied both in terms of its availability and management between different professional groups and teams reflecting, in part, differing levels of motivation towards supporting clinical supervision by individual practitioners and managers as well as a perceived lack of trust leadership. Respondents also reported several potential and actual benefits of clinical supervision, including the improvement and standardization of practice and the facilitation of learning and professional development, although there was no consensus regarding the most appropriate format (e.g. individual, group or team) or structure (e.g. uni-professional or multi-professional) for clinical supervision. It was widely agreed that the introduction of mechanisms for monitoring both the process and outcomes of supervision, greater protection of time allocated for supervision and more training opportunities to increase the skill and number of available supervisors were needed.
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10.12968/bjcn.2004.9.9.15937
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pubmed_747_3358
|
Computerized records of a large university hospital were searched to identify all women from 1967 to 1976 whose conditions had been diagnosed as breast cancer or primary cancer of another site. The records for those women with diagnoses of cancer were then examined to identify any prior psychiatric diagnoses. The rationale was that most patients treated in this hospital setting for psychiatric disorders received neuroleptic drugs, and patients with a diagnosis of schizophrenia are almost certain to be treated with major neuroleptic drugs over a prolonged period of time. No substantial difference in the relative frequency of prior psychiatric treatment was observed between breast cancer and other cancer groups.
|
10.1001/archpsyc.1978.01770310104009
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pubmed_508_2625
|
OBJECTIVES
To observe the effect of both acute and medium-term magnetic stimulation of the pelvic floor on detrusor function amongst women with idiopathic detrusor overactivity (IDO).
METHODS
Two separate studies were undertaken amongst women with a sole diagnosis of IDO. The first study assessed the acute effect of magnetic stimulation (provided by Neocontrol ) on detrusor function during the filling phase of standard cystometry. Multiple filling cycles were performed with stimulation at a different key moment in each. This was done to establish that the device could influence the detrusor. Subsequently, a randomized sham control trial was performed to assess clinical efficacy. A total of 20 treatments, each of 20 minutes duration, were administered over six weeks with follow-up six weeks thereafter. Half the patients received therapy from a genuine device, the others receiving fake treatment on an identical looking/sounding sham device. The sham device contained a deflector plate to degrade the magnetic field and was located in a separate room. Outcome measures included changes in a 24 hour fluid volume chart, urine loss (24 hour pad test) and quality of life instruments.
RESULTS
Amongst 10 patients receiving stimulation during cystometry, volume at first involuntary detrusor contraction during filling rose from a median value of 240ml (Inter-quartile range (IQR) 210-300) to 285ml (IQR 231-320), p = 0.03 and maximum detrusor pressure decreased from 40cm water (IQR 34-45) to 33cm water (IQR 25-41), p<0.01. The RCT was completed by 29 of 44 (66%) recruits. Of these, 15 of 29 (52%) received active treatment and 14 of 29 (48%) sham therapy. Active therapy significantly reduced the number of urge episodes per day, p<0.01. With respect to baseline, actively treated patients experienced significant reduction in voids per day and quality of life but this trend did not reach significance when compared to the sham group, partly due to unexpected difficulty in recruitment which yielded an underpowered sample size for these outcome measures.
CONCLUSIONS
Magnetic stimulation reduces detrusor contractility in the acute phase of administration. Although the treatment was well tolerated and urge episodes reduced following prolonged therapy, no statistically significant improvement was observed in quality of life indices or measured 24 hour urinary loss. The treatment cannot be recommended for women with IDO.
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10.1016/j.eururo.2007.02.026
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pubmed_490_17748
|
A waveguide-mode sensor with a planar sensing chip, consisting of two waveguiding layers and a glass substrate, is a promising candidate for a near-field illumination biosensor. Aiming at using fluorescent labeling induced by ultraviolet light, we optimize the structure of a waveguide-mode sensing chip, based on the mechanism for enhancing ultraviolet near-field light revealed by numerical calculations. Candidates of optimal materials are also presented. The chip optimized as above should be able to enhance the intensity of ultraviolet near-field light 25 times as high as an Al surface plasmon resonance sensing chip.
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10.1364/OE.25.026011
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pubmed_789_6583
|
The dried flower buds of Magnolia sp. are widely used as herbal medicines because of their anti-inflammatory, anti-malarial and anti-platelet activities. Here, we found that veraguensin and galgravin, lignan compounds derived from Magnolia sp., dose-dependently inhibited osteoclast formation in co-cultures of bone marrow cells and osteoblastic cells. These compounds also inhibited receptor activator of nuclear factor κB ligand (RANKL)-induced osteoclast differentiation in RAW264.7 cells and bone marrow macrophages. In the RANKL-induced signaling pathway, veraguensin and galgravin reduced p38 phosphorylation and suppressed the expression of c-Fos, a key transcription factor for osteoclastogenesis. Veraguensin and galgravin also inhibited osteoclastic pit formation, which was accompanied by decreased mature osteoclast viability. In conclusion, these results indicate that veraguensin and galgravin can inhibit bone resorption and may offer novel compounds for the development of drugs to treat bone-destructive diseases such as osteoporosis.
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10.1007/s10616-011-9416-z
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pubmed_447_2553
|
Mycalamide A and mycalamide B, isolated as antiviral and antitumor agents from a New Zealand sponge of the genus Mycale, converted the morphology of ras-transformed NRK-cells to normal morphology at 10 and 1 ng/ml, respectively. The effect on protein synthesis suggests that these agents converted the morphology by preferentially inhibiting the biosynthesis of p21 protein.
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10.1248/cpb.39.2152
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pubmed_471_5551
|
Mixed phospholipid micelles (bicelles) are widely applied in nuclear magnetic resonance (NMR) studies of membrane proteins in solution, as they can solubilize these proteins and provide a membrane-like environment. In this work, the structure of bicelles of dihexanoyl phosphatidyl choline (DHPC) and dimyristoyl phosphatidyl choline (DMPC) at different ratios was determined by small-angle X-ray scattering (SAXS) at 37 °C. Samples with concentrations as applied for NMR measurements with 28 wt % lipids were diluted to avoid concentration effects in the SAXS data. The DMPC/DHPC ratio within the bicelles was kept constant by diluting with solutions of finite DHPC concentrations, where the concentration of free DHPC is the same as in the original solution. Absolute-scale modeling of the SAXS data using molecular and concentration constraints reveals a relatively complex set of morphologies of the lipid aggregates as a function of the molar ratio Q of DMPC to DHPC. At Q = 0 (pure DHPC lipids), oblate core-shell micelles are present. At Q = 0.5, the bicelles have a tablet-shaped core-shell cylindrical form with an ellipsoidal cross section. For Q = 1, 2, 3.2, and 4, the bicelles have a rectangular cuboidal structure with a core and a shell, for which the overall length and width increase with Q. At Q = ∞ (pure DMPC), there is coexistence between multilamellar structures and free bilayers. For Q = 1-4, the hydrocarbon core is relatively narrow and the headgroup thickness on the flat areas is larger than that of, respectively, pure DHPC and DMPC, suggesting some mixing of DHPC into these areas and staggering of the molecules. This is further supported by comparisons of the ratio of the areas of rim and flat parts and estimates of the composition of the flat areas.
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10.1021/acs.langmuir.8b02704
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pubmed_515_25392
|
Zebrafish is gaining popularity in behavioral neuroscience in general and in alcohol research in particular. Alcohol is known to affect numerous molecular mechanisms depending on dose and administration regimen. Prominent among these mechanisms are several neurotransmitter systems. Here we analyze the responses of the dopaminergic and serotoninergic neurotransmitter systems of zebrafish to acute alcohol treatment (1 h long exposure of adult fish to 0.00%, 0.25%, 0.50%, or 1.00% ethyl alcohol) by testing the concentration of dopamine, its metabolite DOPAC, and serotonin and its metabolite 5-HIAA from whole brain extracts. We utilize a sensitive HPLC method and describe significant alcohol induced changes in zebrafish for the first time. We show that dopamine significantly increased in a quasi-linear dose dependent manner, DOPAC showed a smaller apparent increase which was non-significant, while both serotonin and 5-HIAA showed a significant increase only in the highest acute dose group. We discuss the methodological novelty of our work and theorize about the implications of the neurotransmitter level changes from a behavioral perspective.
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10.1016/j.bbr.2009.01.016
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pubmed_1111_13498
|
BACKGROUND
Hypocretins (orexins) are hypothalamic neuropeptides which are involved in a wide range of physiological processes in mammals including central pain processing. Genetic studies in humans evidenced a role for the hypocretinergic system in cluster headache (CH).
PATIENTS AND METHODS
We tested cerebrospinal fluid (CSF) hypocretin-1 (orexin-A) levels in 10 CH patients during an active cluster period. CSF hypocretin-1 levels were measured by radioimmunoassay.
RESULTS
CSF hypocretin-1 levels were within the normal range (mean 457.3±104.98 pg/ml, range 304-639) in our 10 patients, with a slight reduction in one case (304 pg/ml). There were no associations between CSF hypocretin-1 levels and the clinical features of CH. A trend towards higher hypocretin-1 levels was disclosed in patients with chronic CH compared to episodic CH.
CONCLUSIONS
CSF hypocretin-1 levels seem not to influence the clinical course of CH, but our results cannot completely exclude a functional involvement of the hypothalamic hypocretinergic system in the pathogenesis of CH.
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10.1177/0333102411403634
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pubmed_196_20327
|
Tau hyperphosphorylation, mostly at serine (Ser) or threonine (Thr) residues, plays a key role in the pathogenesis of Alzheimer disease (AD) and other tauopathies. Rodent studies show similar hyperphosphorylation in the developing brain, which may be involved in regulating axonal growth and plasticity, but detailed human studies are lacking. Here, we examine tau phosphorylation by immunohistochemistry and immunoblotting in human fetal and adult autopsy brain tissue. Of the 20 cases with sufficient tissue preservation, 18 (90%) showed positive staining for S214 (pSer214), with the majority also positive for CP13 (pSer202), and PHF-1 (pSer396/pSer404). AT8 (pSer202/pThr205) and RZ3 (pThr231) were largely negative while PG5 (pSer409) was negative in all cases. Immunoblotting showed tau monomers with a similar staining pattern. We also observed phospho-tau aggregates in the fetal molecular layer, staining positively for S214, CP13, and PHF1 and negative for thioflavin S. These corresponded to high-molecular weight (∼150 kD) bands seen on Western blots probed with S214, PHF1, and PG5. We therefore conclude that fetal phosphorylation overlaps with AD in some residues, while others (e.g. T231, S409) appear to be unique to AD, and that tau is capable of forming nontoxic aggregates in the developing brain. These findings suggest that the fetal brain is resilient to formation of toxic aggregates, the mechanism for which may yield insights into the pathogenesis of tau aggregation and toxicity in the aging brain.
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10.1093/jnen/nlz073
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pubmed_567_22397
|
The role and fate of B cells in the central nervous system (CNS) in experimental autoimmune encephalomyelitis (EAE) are unknown. Using enzyme-linked immunospot assays we now show that B cells reactive to myelin basic protein (MBP) accumulate in the CNS of Lewis rats with acute EAE induced by immunization with MBP and adjuvants. We also report that B cells are eliminated from the CNS by apoptosis during spontaneous recovery from this disease. Apoptotic B cells were identified by flow cytometry of inflammatory cells extracted from the spinal cord and by histological sections of the spinal cord using light and electron microscopic immunocytochemistry. B cell apoptosis occurred preferentially in the CNS rather than in the peripheral lymphoid organs and was maximal just prior to the onset of spontaneous clinical recovery. Three colour flow cytometry indicated that B cells expressing CD95 (Fas) or CD95 ligand (CD95L) were highly vulnerable to apoptosis, whereas B cells expressing Bcl-2 were relatively protected from apoptosis. We propose that B cells are eliminated from the CNS by the interaction of CD95L and CD95 on the same B cell and that this contributes to the spontaneous resolution of CNS inflammation and clinical recovery in acute EAE.
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10.1006/jaut.2000.0363
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pubmed_77_3607
|
Nineteen hypertensive patients were treated with increasing doses of the new angiotensin-converting enzyme inhibitor MK 421. Twenty milligrams orally reduced blood pressure from 180/112 +/- 6.8/3.6 (mean +/- SEM) to 160/100 +/- 6.5/3.3 mm Hg (p less than 0.005) while heart rate increased from 75 +/- 2 to 87 +/- 3 beats/min (p less than 0.005). Plasma converting enzyme activity was still markedly reduced 24 h following 2.5, 5, 10, or 20 mg MK 421 p.o. (p less than 0.001). In nine patients treated with 20 mg b.i.d. for up to 10 months, blood pressure was controlled, with the association of hydrochlorothiazide 50 mg q.d. in five. However, 12 to 16 h following the preceding drug administration, plasma angiotensin II and aldosterone were back to base-line levels. Analysis of plasma angiotensin II-renin relationships strongly suggests that converting enzyme blockade is not complete even 4 h after 20 mg MK 421 and starts to wear off already at 12 h. Thus, MK 421 20 mg taken orally twice daily, effectively reduces blood pressure, but does not constantly suppress plasma angiotensin II and aldosterone. Whether its long duration of action makes once daily administration possible has not yet been established.
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pubmed_77_3607
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pubmed_460_15309
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Mice lacking dopamine D2 receptors exhibit a significantly decreased agonist-promoted forebrain neocortical D1 receptor activation that occurs without changes in D1 receptor expression levels. This raises the possibility that, in brains of D2 mutants, a substantial portion of D1 receptors are uncoupled from their G protein, a phenomenon known as receptor desensitization. To test this, we examined D1-agonist-stimulated [35S]GTPgammaS binding (in the presence and absence of protein phosphatase inhibitors) and cAMP production (in the presence and absence of pertussis toxin) in forebrain neocortical tissues of wild-type mice and D2-receptor mutants. These studies revealed a decreased agonist-stimulated G-protein activation in D2 mutants. Moreover, whereas protein phosphatase 1/2A (PP1/2A) and 2B (PP2B) inhibitors decrease [35S]GTPgammaS binding in a concentration-dependent manner in wild type, they have either no (PP2B) or only partial (PP1/2A) effects in D2 mutants. Furthermore, for D2 mutants, immunoprecipitation experiments revealed increased basal and D1-agonist-stimulated phosphorylation of D1-receptor proteins at serine residues. Finally, D1 immunoprecipitates of both wild type and D2 mutants also contain protein kinase A (PKA) and PP2B immunoreactivities. In D2 mutants, however, the catalytic activity of the immunoprecipitated PP2B is abolished. These data indicate that neocortical D1 receptors are physically linked to PKA and PP2B and that the increased phosphorylation of D1 receptors in brains of D2 mutants is due to defective dephosphorylation of the receptor rather than increased kinase-mediated phosphorylation.
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10.1111/j.1471-4159.2004.02562.x
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pubmed_798_10511
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The Bcl-x(L)/Bak protein-protein interaction has emerged as an important target for cancer therapy due to its role in apoptosis. Inhibition of this interaction by small-molecule antagonists induces apoptosis in unhealthy cells. Bak, a pro-apoptotic Bcl-2 protein, projects four hydrophobic side chains (V74, L78, I81, and I85), corresponding to the i, i+4, i+7, and i+11 positions of an alpha-helix, into a hydrophobic cleft on Bcl-x(L). Herein, we present a novel family of rationally designed alpha-helix mimetics with improved solubility and synthetic feasibility based on a benzoylurea scaffold. These benzoylurea derivatives favor a linear conformation stabilized by an intramolecular hydrogen bond, and are able to mimic the spatial projection of the i, i+4, and i+7 residues of an alpha-helix. The binding of the benzoylurea derivatives to Bcl-x(L) was assessed using fluorescence polarization competition assays, isothermal titration calorimetry, and (15)N-HSQC experiments. These experiments showed that these agents bind to and disrupt Bcl-x(L) with low micromolar inhibition and dissociation constants, with (15)N-HSQC experiments confirming binding to the hydrophobic pocket of Bcl-x(L) normally occupied by the Bak helix.
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10.1002/cmdc.200800387
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pubmed_1047_9998
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We discovered recently that a subset of mouse anti-streptococcal mAbs cross-reacted with N-acetyl-beta-D-glucosamine (GlcNAc) and certain cytoskeletal proteins, and recognized both carbohydrate and peptide antigenic determinants. To further study the nature and biologic significance of immunologic mimicry between carbohydrate and peptide Ags, eight human hybridomas secreting anti-GlcNAc mAbs were produced by in vitro stimulation of PBL with streptococcal peptidoglycan-polysaccharide complexes and pokeweed mitogen. All human anti-GlcNAc mAbs described in this study were shown to express marked cross-reactivity with keratin from human skin in the ELISA and Western immunoblot. Mapping of the mAbs with overlapping synthetic decapeptides of the entire amino acid sequence of human cytokeratin 14 revealed that human anti-GlcNAc mAbs recognized specific cytokeratin decapeptides. Four human anti-GlcNAc mAbs recognized a single cytokeratin decapeptide whereas two mAbs reacted with several individual peptide epitopes in different fragments of cytokeratin 14. In addition, two mAbs, 1.C8 and 9.B12, reacted with multiple cytokeratin decapeptides, predominantly in the head domain of the molecule, and their reactivity correlated with positive binding of the mAbs to cytokeratin 14 in the Western immunoblot and with positive staining of human epidermis in the indirect immunofluorescent assay. Finally, we demonstrated that Abs to keratin and synthetic keratin decapeptides were induced in BALB/c mice immunized with GlcNAc-BSA but not with BSA, suggesting that the anti-keratin Ab response in vivo may be driven by nonkeratin Ags containing terminal O-linked GlcNAc.
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pubmed_1047_9998
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pubmed_1051_17976
|
Cancer is the most lethal disease that may be found anywhere globally. Approximately 10% of individuals die due to cancer of various types, with 19.3 million new cancer cases and 10 million deaths reported in 2020. More than 100 medications are commercially available for the treatment of cancer, but only a few candidates have high specificity, resulting in several side effects. The scientific community has spent the past decades focusing on drug discovery. Natural resources are used to isolate pharmaceutically active candidates, which are then synthesized in laboratories. More than 60% of all prescribed drugs are made from natural ingredients. Unique five-membered heteroaromatic center motifs with sulfur, oxygen and nitrogen atoms are found in heterocyclic compounds, such as indazole, thiazole, triazole, triazole, and oxazole, and are used as a core scaffold in many medicinally important therapies. Triazole possesses a wide range of pharmacological activities, including anticancer, antibacterial, antifungal, antibiotic, antiviral, analgesic, anti-inflammatory, anti-HIV, antidiabetic, and antiprotozoal activities. Novel triazole motifs with a variety of biological characteristics have been successfully synthesized using versatile synthetic methods. We intend here to facilitate the rational design and development of innovative triazole-based anti-cancer medicines with increased selectivity for various cancer cell lines by providing insight into various ligand-receptor interactions.
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10.2174/1871520622666220217161346
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pubmed_636_19871
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A long-standing paradigm in B cell immunology is that effective somatic hypermutation and affinity maturation require cycling between the dark zone and light zone of the germinal center. The cyclic re-entry hypothesis was first proposed based on considerations of the efficiency of affinity maturation using an ordinary differential equations model for B cell population dynamics. More recently, two-photon microscopy studies of B cell motility within lymph nodes in situ have revealed the complex migration patterns of B lymphocytes both in the preactivation follicle and post-activation germinal center. There is strong evidence that chemokines secreted by stromal cells and the regulation of cognate G-protein coupled receptors by these chemokines are necessary for the observed spatial cell distributions. For example, the distribution of B cells within the light and dark zones of the germinal center appears to be determined by the reciprocal interaction between the level of the CXCR4 and CXCR5 receptors and the spatial distribution of their respective chemokines CXCL12 and CXCL13. Computer simulations of individual-based models have been used to study the complex biophysical and mechanistic processes at the individual cell level, but such simulations can be challenging to parameterize and analyze. In contrast, ordinary differential equations are more tractable, but traditional compartment model formalizations ignore the spatial chemokine distribution that drives B cell redistribution. Motivated by the desire to understand the motility patterns observed in an individual-based simulation of B cell migration in the lymph node, we propose and analyze the dynamics of an ordinary differential equation model incorporating explicit chemokine spatial distributions. While there is experimental evidence that B cell migration patterns in the germinal center are driven by extrinsically regulated differentiation programs, the model shows, perhaps surprisingly, that feedback from receptor down-regulation induced by external chemokine fields can give rise to spontaneous interzonal and intrazonal oscillations in the absence of any extrinsic regulation. While the extent to which such simple feedback mechanisms contributes to B cell migration patterns in the germinal center is unknown, the model provides an alternative hypothesis for how complex B cell migration patterns might arise from very simple mechanisms.
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10.1007/s11538-012-9799-9
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pubmed_1111_22634
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In this work, the effects of crystalline structure of the TiO2, which is incorporated in fabrication of the n-type electrode, on the DSSC performance were investigated in terms of the energy conversion efficiency. In this effort, TiO2 nanoparticle pastes with varying contents of rutile and anatase structures were prepared by using the ethanol mixing method. The most efficient photo-electro-chemical performance was achieved for the DSSC fabricated with the TiO2 paste in which the anatase form of the nanocrystal extends to 90%.
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10.1166/jnn.2011.3419
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pubmed_986_973
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A case of pseudochylous thoracic effusion associated with feline cardiomyopathy is described. At necropsy there was no evidence of structural damage to the thoracic duct or other major lymphatic vessels. The literature covering this syndrome was reviewed and it was concluded that the thoracic effusion may have been associated with congestive heart failure and interference with drainage of the thoracic duct into the anterior vena cava.
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10.1111/j.1751-0813.1982.tb02693.x
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pubmed_599_5158
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Arrays of highly ordered silicon nanowire (SiNW) clusters are fabricated using complementary metal-oxide semiconductor (CMOS) field effect transistor-compatible technology, and the ultrasensitive, label-free, electrical detection of cardiac biomarker in real time using the array sensor is presented. The successful detection of human cardiac troponin-T (cTnT) has been demonstrated in an assay buffer solution of concentration down to 1 fg/mL, as well as in an undiluted human serum environment of concentration as low as 30 fg/mL. The high specificity, selectivity, and swift response time of the SiNWs to the presence of ultralow concentrations of a target protein in a biological analyte solution, even in the presence of a high total protein concentration, paves the way for the development of a medical diagnostic system for point-of-care application that is able to provide an early and accurate indication of cardiac cellular necrosis.
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10.1021/ac901157x
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pubmed_893_1558
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The high-order waveguide modal theory, usually used in electromagnetics and acoustics, is adopted to investigate the propagation properties of shear horizontal waves in a periodic stubbed plate. Beyond the sub-wavelength regime, higher-order modes are included to calculate the exact band structures caused by the stubs. Theoretical solutions are obtained in a closed form, in which both the dynamic governing equations and the boundary conditions are strictly satisfied. It is shown that the proposed modelling approach exhibits good convergence and accuracy, in agreement with results obtained from the finite element method. After a systematic investigation on the influence of the stub on the evolution of the band structures, the so-called rainbow trapping phenomenon of SH waves is revealed and explored in a graded stubbed plate with monotonously increasing height or width of the stubs, featuring an obvious reduction of the group velocity and blocking of the wave propagation at different locations for SH waves of different frequencies. The proposed model is expected to provide a useful theoretical tool for the physical mechanism exploration, structural design and eventually system optimization to guide various engineering applications of SH waves.
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10.1016/j.ultras.2017.11.010
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pubmed_261_8645
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It has been suggested that a deficiency in folic acid during early, critical central nervous system development may result in persistent cognitive and behavioral effects. The purpose of this systematic review was to evaluate evidence regarding whether folic acid supplementation during pregnancy and early life influences mental performance outcomes in children. The following electronic databases were searched through December 2009 for studies relevant to mental performance and folic acid: MEDLINE, EMBASE and The Cochrane Library; additional references were obtained from reviewed articles. Only randomized controlled trials (RCTs) were included. Of 8 RCTs identified, only 2 met the inclusion criteria. Both studies involved periconceptional, multivitamin-containing, folic acid supplementation. Evidence from these 2 RCTs suggests that such supplementation does not affect the postnatal mental development of infants at a mean age of 11 mo, the developmental quotient (DQ) at 2 y of age, or the intelligence quotient (IQ) and Goodenough man drawing test quotient (DrQ) at 6 y of age. We conclude that the use of multivitamin-containing folic acid supplementation during pregnancy is associated with no benefit to the mental performance of children. These findings should be interpreted with caution due to the very limited number of studies included in this systemic review.
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10.1080/10408398.2010.515042
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pubmed_931_5043
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Various animals must cope with some specific extreme environmental conditions and, as a consequence, they developed extremely efficacious adaptive defence responses. The mechanisms of the specific defences are more clearly visible in some species than in humans. Therefore, animal models of the human defence mechanisms should be selected accordingly. The appropriate, well responding models may be regarded as "biological amplifiers". This review is focussed on examples of effective defence against: (i) parturitional asphyxia, which extends fertility of mammals; (ii) diving asphyxia, which extends access of food in aquatic birds and mammals; (iii) endotoxemia, which provides survival of the fittest in mammals showing top fertility; (iv) deep hypothermia, which enables hibernating mammals to arouse. Each of the defences needs close co-operation of the cardiovascular, respiratory and temperature regulatory systems. Underlined problems regarding a choice of appropriate experimental animal models should stimulate renaissance of comparative physiology.
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pubmed_931_5043
|
pubmed_130_19547
|
Adhesion is crucial for the infective lifestyles of bacterial pathogens. Adhesion to non-living surfaces, other microbial cells, and components of the biofilm extracellular matrix are crucial for biofilm formation and integrity, plus adherence to host factors constitutes a first step leading to an infection. Adhesion is, therefore, at the core of pathogens' ability to contaminate, transmit, establish residency within a host, and cause an infection. Several mycobacterial species cause diseases in humans and animals with diverse clinical manifestations. Mycobacterium tuberculosis, which enters through the respiratory tract, first adheres to alveolar macrophages and epithelial cells leading up to transmigration across the alveolar epithelium and containment within granulomas. Later, when dissemination occurs, the bacilli need to adhere to extracellular matrix components to infect extrapulmonary sites. Mycobacteria causing zoonotic infections and emerging nontuberculous mycobacterial pathogens follow divergent routes of infection that probably require adapted adhesion mechanisms. New evidence also points to the occurrence of mycobacterial biofilms during infection, emphasizing a need to better understand the adhesive factors required for their formation. Herein, we review the literature on tuberculous and nontuberculous mycobacterial adhesion to living and non-living surfaces, to themselves, to host cells, and to components of the extracellular matrix.
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10.3390/microorganisms10020454
|
pubmed_300_8783
|
BACKGROUND/AIMS
Clevudine is a nucleoside analogue that exhibits potent and sustained antiviral effects as a 24-week therapy for chronic hepatitis B (CHB). This study evaluated the efficacy and viral resistance of a 48-week course of clevudine treatment for CHB.
METHODS
Data on patients with CHB and detectable serum hepatitis B virus (HBV) DNA who were treated with clevudine for 48 weeks or longer were collected retrospectively for this study. Patients who had taken lamivudine within the 3 years prior to this study were excluded. Serum HBV DNA was measured by polymerase chain reaction hybridization (lower detection limit=316 copies/mL). Serum HBV DNA and biochemical data were analyzed at weeks 24 and 48. Developments of viral breakthrough and resistance to the antiviral drug were also monitored.
RESULTS
Data from 74 patients (mean age 44 years; M:F=54:20; HBeAg-positive, 47; HBeAg-negative, 27) were included in this study. Ten patients had experienced previous lamivudine treatment. Median HBV DNA at baseline was 6.49 log(10) copies/mL. Median serum HBV DNA reductions from baseline at week 48 were -4.34 log(10) copies/mL (HBeAg-positive, -4.84 log(10) copies/mL; HBeAg-negative, -3.74 log(10) copies/mL). At week 48, serum HBV DNA was not detected in 83.8% of the patients (HBeAg-positive, 76.6%; HBeAg-negative, 96.3%). Normalization of serum alanine aminotransferase levels was achieved in 84.7% of the patients. Viral breakthrough and antiviral resistance developed in two patients at week 48. The development of antiviral resistance was associated with the presence of previous lamivudine treatment and cirrhosis.
CONCLUSION
A 48-week course of clevudine therapy was highly effective in patients with CHB. The risk of development of resistance to clevudine was increased in patients with previous exposure to lamivudine and cirrhosis.
|
10.3350/kjhep.2009.15.3.331
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pubmed_1023_9136
|
Male weanling rats were fed four diets providing high or low levels of protein and/or zinc. One group on each diet was sacrificed every 2 weeks to measure the weights of the reproductive organs, plasma levels of follicle-stimulating hormone and luteinizing hormone, and the plasma and testicular concentrations of testosterone, dihydrotestosterone and zinc. The results demonstrate that hypogonadal states are produced in response to protein deficiency and zinc deficiency but the mechanisms involved are different. The specific effects of zinc deficiency are not observed in protein-deficient animals.
|
10.1159/000176781
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pubmed_189_18837
|
The magnetic interactions between the spin of an unpaired electron and the surrounding nuclear spins can be exploited to gain structural information, to reduce nuclear relaxation times as well as to create nuclear hyperpolarization via dynamic nuclear polarization (DNP). A central aspect that determines how these interactions manifest from the point of view of NMR is the timescale of the fluctuations of the magnetic moment of the electron spins. These fluctuations, however, are elusive, particularly when electron relaxation times are short or interactions among electronic spins are strong. Here we map the fluctuations by analyzing the ratio between longitudinal and transverse nuclear relaxation times T1/T2, a quantity which depends uniquely on the rate of the electron fluctuations and the Larmor frequency of the involved nuclei. This analysis enables rationalizing the evolution of NMR lineshapes, signal quenching as well as DNP enhancements as a function of the concentration of the paramagnetic species and the temperature, demonstrated here for LiMg1-xMnxPO4 and Fe(III) doped Li4Ti5O12, respectively. For the latter, we observe a linear dependence of the DNP enhancement and the electron relaxation time within a temperature range between 100 and 300 K.
|
10.1016/j.jmr.2022.107143
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pubmed_603_2942
|
BACKGROUND
Lysosome-associated protein transmembrane 4 beta (LAPTM4B) has two alleles named LAPTM4B*1 and LAPTM4B*2. Allele *1 contains only one copy of a 19-bp sequence at the 5'UTR in the first exon, whereas this sequence of allele*2 is duplicated and arrayed as a tandem repeat. Previous studies revealed that LAPTM4B polymorphisms contribute to the risk of certain types of cancers. This study aimed to investigate the polymorphism of LAPTM4B in breast cancer by analysis the correlation of LAPTM4B genotype with breast cancer susceptibility, clinicopathologic features and prognosis.
METHODS
Genotyping of the LAPTM4B polymorphism was determined by PCR method. The expression levels of LAPTM4B in breast cancer tissues and breast cancer cell lines were determined by quantitative reverse-transcription PCR (qRT-PCR) analysis. The correlation of LAPTM4B genotype with clinicopathologic parameters and prognosis were assessed statistically.
RESULTS
The results of qRT-PCR analysis indicated that LAPTM4B*2 was associated with the higher level of LAPTM4B expression compared with the LAPTM4B*1 in both breast cancer cell lines and breast cancer tissues. We found that LAPTM4B*2 was associated with an increased risk for breast cancer. LAPTM4B*2 was significantly associated with higher histopathologic grade, lymph node metastasis and poor prognosis.
CONCLUSION
LAPTM4B*2 is a risk factor associated with breast cancer susceptibility and poor prognosis. LAPTM4B*2 may be a potential predicative marker for the susceptibility, progression and metastasis of breast cancer.
|
10.1371/journal.pone.0044916
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pubmed_722_4324
|
The liver X receptors (LXRs)-α and -β play a crucial role in control of insulin production and secretion in pancreatic β-cells. We hypothesized that common variants in the NR1H2 and NR1H3 genes, encoding LXR-β and -α, respectively, may alter pancreatic β-cell function. One thousand five hundred seventy-four subjects of European ancestry with elevated risk for type 2 diabetes were genotyped for the two NR1H2 single nucleotide polymorphisms (SNPs) rs2248949 and rs1405655 and for the four NR1H3 SNPs rs11039149, rs3758673, rs12221497 and rs2279238, and association studies with metabolic traits were performed. Metabolic characterization comprised an oral glucose tolerance test (OGTT) in all participants and, in addition, a hyperinsulinemic-euglycemic clamp and an intravenous glucose tolerance test (IVGTT) in subsets. One hundred per cent of common genetic variation (minor allele frequency ≥1%) within the NR1H2 and NR1H3 loci (D' = 1.0; r² ≥ 0.8) were covered by the six chosen tagging SNPs. NR1H2 rs2248949 was nominally associated with OGTT-derived first-phase insulin secretion and proinsulin conversion to insulin and significantly associated with the AUC of insulin levels during the IVGTT (p = 0.007) after adjustment for age, gender, BMI and insulin sensitivity in the dominant model, with the minor allele conferring reduced pancreatic β-cell function to the carriers. In subjects of European ancestry at increased risk for type 2 diabetes, common variation within the NR1H2 gene impaired insulin secretion, which may facilitate the development of type 2 diabetes.
|
10.1007/s00109-010-0687-1
|
pubmed_505_17240
|
The "Holy Grail" of in vitro toxicology is to develop assay systems that mimic the in vivo situation and hence reduce the need for toxicity tests employing experimental animals. However a major problem to be overcome with cell culture models is the rapid loss of differentiated phenotype that markedly limits extrapolation of results to the whole animal (i.e. human) situation. This limitation is most obvious in the application of hepatocyte cultures to predict pathways of metabolism mediated toxicity and results from the rapid loss of cytochrome P450 content. Here we demonstrate that changes in hepatocyte gene expression (e.g. MAP kinase and NF-kappaB activation) occur very early into the well established hepatocyte isolation procedure employing collagenase suggesting that hepatocytes are undergoing a pro-inflammatory ('acute phase') response before they are cultured. Data is presented indicating that the stimulus is, in part, due to oxidative stress but the demonstration of endotoxins in collagenase preparations is likely to exacerbate the situation. Thus appreciation of these early events during hepatocyte isolation represents the surest foundation for the successful application of cultured hepatocytes to toxicology rather than relying on traditional manipulations of hepatocyte culture medium/substratum once differentiated phenotype has already been lost.
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10.1016/s0887-2333(03)00146-2
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pubmed_470_7567
|
BACKGROUND
Multiple A- and B-type cyclins have been identified in animals, but their study is complicated by varying degrees of functional redundancy. A non-essential phenotype may reflect redundancy with a known or as yet unknown gene. Complete sequencing of several animal genomes has allowed us to determine the size of the mitotic cyclin gene family and therefore to start to address this issue.
RESULTS
We analyzed the Caenorhabditis elegans, Drosophila melanogaster and Homo sapiens genomes to identify known and novel A- and B-type cyclin genes and distinguish them from related pseudogenes. We find only a single functional A-type cyclin gene in invertebrates but two in vertebrates. In addition to the single functional cyclin A gene, the C. elegans genome contains numerous cyclin A pseudogenes. In contrast, the number and relationship of B-type cyclins varies considerably between organisms but all contain at least one cyclin B1-like gene and a cyclin B3 gene.
CONCLUSIONS
There are three conserved families of mitotic cyclins in animals: A-, B3- and B-type. The precise number of genes within the A- and B-type families varies in different organisms, possibly as an adaptation to their distinct developmental strategies.
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10.1186/gb-2002-3-12-research0070
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pubmed_564_7576
|
The effect of sheltered workshop activities on the social living activity of the mentally ill was studied in order to evaluate the role and level of function of workshop activities as a self support and employment system for clients, and to determine the future tasks of the workshop and rehabilitative services in the community. The following results were observed: 1) Clients' social living ability appears to be poor, especially in questions related to personal relationships and time distribution, where less than 50% of the clients answered "Possible without assistance". This appears to be characteristics of the living behaviors of mentally ill individuals. 2) Most of the families of the clients evaluated the sheltered workshop activities positively in terms of increasing the clients' social living ability. 3) A survey of families showed that by utilizing the workshop much progress has been made toward improving those living behaviors which are easily made into habits and lifestyle pattern. On the other hand, personal relationships and living behaviors which require coping flexibility, are much more refactory. Based on those results, the future task of sheltered workshops and the supportive role of the public health center need to be examined further.
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pubmed_564_7576
|
pubmed_251_13647
|
Two cases of esophageal duplication cyst associated with pulmonary cystic malformations (cystic bronchiectasis with pneumonia in one, intrapulmonary bronchogenic cysts with bronchial atresia in the other) are reported. The coexistence of these complex anomalies supports the recognition that esophageal duplication cyst also is an entity of a broad spectrum of developmental abnormalities caused by abnormal budding of the primitive foregut. Nine cases of similar complex anomalies in the lung and esophagus have been reported. Although rare, this malformation complex should be borne in mind in the treatment of pediatric mediastinal and pulmonary malformations.
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10.1016/0022-3468(95)90465-4
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pubmed_862_961
|
We present directional hemispherical reflectance (DHR) and bidirectional reflectance distribution function (BRDF) measurements of a carbon aerogel in the 2.5-14.3-microm infrared spectral region. The measured DHR is 1.0-1.2 +/- 0.2% throughout the 2.5-14.3-microm infrared wavelength region. When the incidence angle is increased from 8 degrees to 30 degrees off normal, the DHR increases by only 0.2%; i.e., performance does not significantly degrade as a result of illumination by off-normal infrared radiation. BRDF measurements, obtained at a wavelength of 10.6 microm, indicate that carbon aerogel exhibits Lambertian behavior. The carbon aerogel's BRDF value of 4 x 10(-3) sr(-1) is consistent with its measured DHR values. Gas adsorption and transmission-electron microscopy indicate a structure dominated by particles and pores of <or=10-nm dimension. Scanning-electron microscopy reveals surface roughness on a scale of tens of nanometers. The DHR and BRDF of carbon aerogel compare favorably with those of Martin Black and Rippey, two widely used nonreflective materials.
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10.1364/ao.39.003940
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pubmed_55_3110
|
The most recent forecast by international agencies predicted there would be between 9,000 and 28,000 fatal cancers between 1986 and 2056, obviously underestimating the risk factors and the collective doses. On the basis of I-131 and Cs-137 radioisotope doses to which populations were exposed and a comparison of cancer mortality in the heavily and the less contaminated territories and pre- and post-Chernobyl cancer levels, a more realistic figure is 212,000 to 245,000 deaths in Europe and 19,000 in the rest of the world. High levels of Te-132, Ru-103, Ru-106, and Cs-134 persisted months after the Chernobyl catastrophe and the continuing radiation from Cs-137, Sr-90, Pu, and Am will generate new neoplasms for hundreds of years.
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10.1111/j.1749-6632.2009.04827.x
|
pubmed_768_20536
|
BACKGROUND
Cancer stem cells (CSCs) are a subset of tumor cells with capacity to self-renew and generate the diverse cells that make up the tumor. The aim of this study is to evaluate the prognostic value of CSCs in a highly homogeneous population of stage II colon cancer.
METHODS
One hundred stage II colon cancer patients treated by the same surgical team between 1977 and 2005 were retrospectively analyzed. None of the patients received adjuvant chemotherapy. Inmunohistochemistry expression of CD133, NANOG and CK20 was scored, using four levels: <10%, 11-25%, 26-50% and >50% positivity. Kaplan-Meier analysis and log rank test were used to compare survival.
RESULTS
The average patient age was 68 years (patients were between 45-92 years of age) and median follow up was 5.8 years. There was recurrent disease in 17 (17%); CD133 expression (defined by >10% positivity) was shown in 60% of the tumors, in 95% for NANOG and 78% for CK20. No correlation was found among expression levels of CD133, NANOG or CK20 and relapse-free survival (RFS) or overall survival (OS). However, a statistical significant correlation was found between established pathological prognostic factors and RFS and OS.
CONCLUSIONS
Stem Cell quantification defined by CD133 and NANOG expression has no correlation with RFS or OS in this cohort of Stage II colon cancer.
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10.1371/journal.pone.0088480
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pubmed_658_5200
|
Nocardiosis (NOC) is an important cause of infection in immunocompromised patients. However, large series in patients with cancer have not been described. We review the records of patients with cancer and NOC who were evaluated at The University of Texas M. D. Anderson Cancer Center, Houston, Texas, between 1988 and 2001, and we describe the incidence, microbiologic and clinical characteristics, treatment, and outcome of NOC in this population. Forty-two patients with a total of 43 episodes of NOC were identified (incidence of 60 cases of NOC per 100,000 admissions). Twenty-seven patients (64%) had hematologic malignancies. In 13 patients, NOC complicated bone marrow transplantation. Neutropenia was observed in 4 (10%) of 40 episodes with information available, and lymphopenia in 20 (50%) of 40 episodes. Patients had received steroids for 25 episodes (58%) and had received chemotherapy for 10 episodes (23%) within 30 days before the onset of NOC. Nine episodes of breakthrough NOC were identified in 7 (23%) of the 40 patients with information available. Pulmonary NOC was seen in 30 (70%) of 43 cases; soft-tissue NOC in 7 (16%); central venous catheter-related nocardemia in 3 (7%); and disseminated NOC, central nervous system NOC, and a perinephric abscess each in 1 (2%). Twenty-three percent of patients with pulmonary NOC had an acute presentation. complex was the most common causative species (77%). Therapy for NOC was mainly concurrent trimethoprim/ sulfamethoxazole and either a tetracycline or a beta-lactam. The median duration of treatment was 113 days (range, 10-600 d). Nine (60%) of 15 patients with outcome data died from NOC. NOC, although infrequent, is an important cause of morbidity and mortality in patients with cancer. It has pleomorphic manifestations, and it can be seen as a breakthrough infection. The present study confirms that timely diagnosis, the site of NOC, the type of, the presence of comorbidities, and cytomegalovirus coinfection influence the outcome of patients with cancer and NOC.
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10.1097/00005792-200209000-00004
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pubmed_294_6710
|
The recent advancements in diagnosis and treatment of thoracic disease have been made mostly in line with advancements in endoscopic equipment design and refinement of thoracoscopic surgery techniques. Between March 1992 and February 1993, video thoracoscopic procedures were performed in 50 patients. Twelve of the 50 patients were diagnosed with lung cancer. Thoracic staging was performed in 6 patients (clinical diagnosis of suspicious intrapulmonary metastasis, 3 patients; intrapulmonary metastasis and/or lymph node metastasis, 1 patient; interlobar pleural effusion, 1 patient; and pleural dissemination, 1 patient). There were no complications or mortality associated with these procedures. Our initial experience has indicated that thoracoscopic staging for lung cancer is a safe and effective procedure.
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10.1016/0003-4975(93)90945-e
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pubmed_499_3952
|
Membranes with high permeance and high rejection for di- and multivalent cation removal are highly desired for efficient brackish water and industrial water treatment. In this work, we report a facile strategy for constructing ultrathin nanofiltration (NF) membranes by in situ cross-linking of amine which is confined in a network film. The network made of single-walled carbon nanotubes (SWCNTs) serves as a framework for poly(ethylene imine) (PEI) to attach and stay, facilitating the formation of a polyamine (PA) layer with high quality and controlled thickness. Benefiting from the ultrathin thickness of the SWCNT network (∼31 nm), an active layer (∼34 nm thick) comes with a high permeance of 27 L m-2 h-1 bar-1 along with a high rejection of 97% to MgCl2, 2-5 times higher than the NF membranes with the same high rejection for MgCl2 reported so far. In addition, the SWCNT-interpenetrated PA structure endows the ultrathin NF membrane with good operational stability. This work demonstrates the capability to control the position, thickness, and even quality of the PA layer by using a confined framework and provides a feasible strategy for the fabrication of highly permeable ultrathin NF membranes with a reinforced active layer.
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10.1021/acsmacrolett.9b00624
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pubmed_219_8993
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The clavicle fractures managed non-operatively have shown a high prevalence of symptomatic malunion and non-union. We sought to compare patient-oriented outcome and complication rates following non-operative treatment and those after operative treatment of clavicular fractures. In a prospective randomised study, 30 patients with 30 clavicle fractures were randomised by systemic allocation to either operative treatment or non-operative treatment. Fifteen patients were in each group. Outcome analysis included standard clinical follow-up and the disability of the arm, shoulder and hand (DASH) score, and plain radiographs. The mean follow-up of both groups were 12.56 months. DASH scores were significantly improved in the operative fixation group at all time-points. The mean time to radiographic union was 27.46 weeks in the non-operative group compared with 15.73 weeks in the operative group (p = 0.000). There were no non-unions in both groups. Symptomatic malunion developed in seven patients (46.66%) in the non-operative group and in none in the operative group. The complications in the operative group were hardware-irritation (one case) and incisional numbness (one case). At final follow-up, the patients in the operative group were more satisfied with the appearance of the shoulder (p = 0.039) and with the shoulder in general than were those in the non-operative group. There were no differences between the two groups with respect to patient age, sex, side of injury or associated injuries. Operative fixation of AO type B2 clavicular fracture results in improved functional outcome and early union compared with non-operative treatment at one year of follow-up. This study supports primary operative fixation of completely displaced mid shaft clavicular fractures in active adult patients.
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pubmed_219_8993
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pubmed_705_3609
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The long-term results were reviewed for seventy-two patients (seventy-five knees) who had had a bone-patellar ligament-bone intra-articular reconstruction of the anterior cruciate ligament between August 1984 and May 1992. The mean age of the patients at the time of the operation was forty-five years (range, forty to sixty years). Three patients had a bilateral procedure. The primary mechanisms of injury were accidents that occurred during skiing (thirty-two knees), tennis (fourteen knees), and soccer (five knees). We analyzed the responses to subjective questionnaires, the functional results, and the objective clinical data. The clinical examination included assessment of the range of motion, performance of Lachman and pivot-shift tests, and measurements with use of a KT-1000 arthrometer. All knees were evaluated with use of three common rating scales: that of Lysholm and Gillquist; that of The Hospital for Special Surgery, as modified by Insall et al.; and the International Knee Ligament Standard Evaluation Form. At the latest follow-up evaluation, at a mean of fifty-five months (range, twenty-six to 117 months), three patients reported pain or swelling. No patient reported giving-way or symptoms related to the patellofemoral joint. The mean range of extension was -12 to 6 degrees, compared with -8 to 42 degrees preoperatively, and the mean range of flexion was 112 to 150 degrees, compared with 52 to 154 degrees preoperatively. Flexion was limited to 112 degrees in one patient, but this was 5 degrees greater than that of the uninvolved knee. Sixty knees (80 per cent) had a negative pivot-shift test, and ten knees (13 per cent) had a grade of 1+. On testing with the KT-1000 device at maximum manual pressure, the mean difference between the injured and uninjured knees was found to have improved by 5.1 millimeters, from 6.4 millimeters preoperatively to 1.4 millimeters postoperatively (p < 0.01). The grade on the International Knee Ligament Standard Evaluation Form improved markedly; seventy-two knees (96 per cent) had a grade of C or D preoperatively, whereas seventy knees (93 per cent) had a grade of A or B postoperatively. The Hospital for Special Surgery score improved from a mean of 69 points preoperatively to a mean of 92 points postoperatively (p < 0.01). The mean score according to the scale of Lysholm and Gillquist increased from a mean of 63 points preoperatively to a mean of 94 points postoperatively (p < 0.01). All patients indicated that they were pleased with the result of the procedure. Bicycling was resumed at a mean of four months; jogging, at a mean of nine months; skiing, at a mean of ten months; and tennis, at a mean of twelve months.
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10.2106/00004623-199802000-00005
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pubmed_277_6900
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Thrombocytopenia is common among sick neonates. Certain groups of thrombocytopenic adults respond favorably to the administration of recombinant thrombopoietin or to pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF), a recombinant human polypeptide that contains the receptor-binding N-terminal domain of thrombopoietin. The effectiveness and safety of such treatment in neonates, however, have not been reported. The purpose of the present study was to determine the biologic activity and safety of PEG-rHuMGDF administration to newborn rhesus monkeys. Eight monkeys were divided into four groups and treated subcutaneously with 0.00, 0.25, 1.00, or 2.50 microg/kg once daily for 7 d. Complete blood counts, serum chemistries, clotting panels, and MGDF levels were followed serially, and hematopoietic progenitor cell assays were performed on bone marrow aspirates before the first dose and again on d 8. Pharmacokinetic evaluations were performed on the animals that received the highest dose of PEG-rHuMGDF. All monkeys had normal growth during the study period, and all chemistries, clotting studies, and blood pressure measurements were normal. The peak serum MGDF concentration occurred at 3 h, and the half-life was 8.4 to 13.0 h. As in adult rhesus monkeys, platelet counts in the treated neonates began to rise on d 6, peaked on d 11, and returned to baseline by d 23. The two highest doses generated an 8- to 12-fold increase in platelets, whereas those treated with 0.25 microg/kg had a 6-fold increase. Other hematologic parameters measured were unaffected. Thus, newborn monkeys responded to doses of PEG-rHuMGDF that were similar to or smaller than (per kilogram body weight) those that are effective in adult animals and did so without obvious short-term toxicity.
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10.1203/00006450-200002000-00010
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pubmed_150_17819
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The purpose of this study was to investigate whether immersion of a denture surface in lemongrass extract (LGE) has effects on C. albicans biofilms, human cell viability and denture surface. Minimal inhibitory concentration (MIC) and minimal fungicidal concentration (MFC) were performed for LGE against C. albicans. For biofilm analysis, discs were fabricated using a denture acrylic resin with surface roughness standardization. C. albicans biofilms were developed on saliva-coated discs, and the effects of LGE at MIC, 5XMIC, and 10XMIC were investigated during biofilm formation and after biofilm maturation. Biofilms were investigated for cell counting, metabolic activity, and microscopic analysis. The cytotoxicity of different concentrations of LGE to peripheral blood mononuclear cells (PBMC) was analyzed using MTT. The effects of LGE on acrylic resin were verified by measuring changes in roughness, color and flexural strength after 28 days of immersion. Data were analyzed by ANOVA, followed by a Tukey test at a 5% significance level. The minimal concentration of LGE required to inhibit C. albicans growth was 0.625 mg/mL, while MFC was 2.5 mg/mL. The presence of LGE during biofilm development resulted in a reduction of cell counting (p < 0.05), which made the MIC sufficient to reduce approximately 90% of cells (p < 0.0001). The exposure of LGE after biofilm maturation also had a significant antifungal effect at all concentrations (p < 0.05). When compared to the control group, the exposure of PBMC to LGE at MIC resulted in similar viability (p > 0.05). There were no verified differences in color perception, roughness, or flexural strength after immersion in LGE at MIC compared to the control (p > 0.05). It could be concluded that immersion of the denture surface in LGE was effective in reducing C. albicans biofilms with no deleterious effects on acrylic properties at MIC. MIC was also an effective and safe concentration for use.
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10.3389/fcimb.2016.00071
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pubmed_49_9464
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During a one-year observation period eleven patients treated with fixed appliances and 164 brackets which had been bonded in pairs, were checked at periodic intervals. Every patient had brackets positioned on the teeth in the first and fourth quadrant without graphite marking and in the second and third quadrant with graphite marking. In a parallel in-vitro study with eight pairs of teeth the above described conditions were applied. These specimens were examined in an universal testing machine in order to determine the magnitude of the shear forces. In the in-vivo as well as in the in-vitro study no statistically significant correlations were revealed between the graphite marking and the durability of adhesion as well as the required shear force of the examined brackets. Utilising light microscopy studies, the penetration of adhesive was determined in relation to the position of the graphite marking in etched enamel; at was harmlessness of the reference medium.
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10.1007/BF02166851
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pubmed_151_676
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A wide range of trace organic contaminants (TOrCs), including the endocrine-disrupting compound bisphenol A (BPA), are subject to microbial transformations during biological wastewater treatment. However, relatively little is known about the identity of organisms capable of assimilating emerging contaminants. Here, 13C-DNA stable isotope probing (DNA-SIP) was used to investigate biodegradation and assimilation of BPA by mixed microbial communities collected from two full-scale wastewater treatment plant bioreactors in New York City and subsequently enriched under two BPA exposure conditions. The four enrichment modes (two reactors with two initial BPA concentrations) resulted in four distinct communities with different BPA degradation rates. On the basis of DNA-SIP, bacteria related to Sphingobium spp. were dominant in the assimilation of BPA or its metabolites. Variovorax spp. and Pusillimonas spp. also assimilated BPA or its metabolites. Our results highlight that microbial communities originating from wastewater treatment facilities harbor the potential for addressing not only human-derived carbon but also BPA, a complex anthropogenic TOrC. While previous studies focus on microbial biodegradation of BPA, this study uniquely determines the "active" fraction of microorganisms engaged in assimilation of BPA-derived carbon. Ultimately, information on both biodegradation and assimilation can facilitate better design and operation of engineered treatment processes to achieve BPA removal.
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10.1021/acs.est.8b01976
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pubmed_785_11544
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BACKGROUND
To describe the reference values for the Spanish version of the Breastfeeding Self-Efficacy Scale-Short Form (BSES-SF), considering the differences according to parity and previous breastfeeding experience.
METHODS
Cross-sectional study in five hospitals in Valencia and one in Murcia, Spain, in a convenience sample of 949 in-hospital breastfeeding women, with no medical problems in the mothers or newborns hindering breastfeeding. Data on sociodemographic and obstetric variables, and on breastfeeding self-efficacy, were collected using the BSES-SF. Central tendency, dispersion and percentile data were calculated to generate reference values for the entire sample, and by parity and previous experience.
RESULTS
The level of self-efficacy was significantly lower (p <0.001) among primiparous women (mean =47.67±11.03) or those without previous experience (mean =47.30±11.18) than among multiparas (mean =52.87±10.66) or women with previous experience (mean =53.93±9.93). The P25 and P75 percentiles for the BSES-SF were, respectively, 42 and 59 for the entire sample; 39 and 56 for women without children or without previous experience; 46 and 61 for mothers with children; and 47 and 62 for mothers with previous experience.
CONCLUSIONS
The specific percentiles obtained by parity or previous experience should be considered the reference values for comparing the level of self-efficacy of a given case, and for evaluating and planning educational postpartum support interventions.
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10.4321/s1137-66272014000200003
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pubmed_83_8863
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Musculoskeletal disorders are one of the major health burdens and a leading source of disability worldwide, affecting both juvenile and elderly populations either as a consequence of ageing or extrinsic factors such as physical injuries. This condition often involves a group of locomotor structures such as the bones, joints and muscles and may therefore cause significant economic and emotional impact. Some pharmacological and non-pharmacological treatments have been considered as potential solutions, however, these alternatives have provided quite limited efficacy due to the short-term effect on pain management and inability to restore damaged tissue. The emergence of novel therapeutic alternatives such as the application of orthobiologics, particularly bone marrow aspirate (BMA) clot, have bestowed medical experts with considerable optimism as evidenced by the significant results found in numerous studies addressed in this manuscript. Although other products have been proposed for the treatment of musculoskeletal injuries, the peculiar interest in BMA, fibrin clot and associated fibrinolytic mechanisms continues to expand. BMA is a rich source of various cellular and molecular components which have demonstrated positive effects on tissue regeneration in many in vitro and in vivo models of musculoskeletal injuries. In addition to being able to undergo self-renewal and differentiation, the hematopoietic and mesenchymal stem cells present in this orthobiologic elicit key immunomodulatory and paracrine roles in inflammatory responses in tissue injury and drive the coagulation cascade towards tissue repair via different mechanisms. Although promising, these complex regenerative mechanisms have not yet been fully elucidated.
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10.1016/j.jcot.2020.07.003
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pubmed_1013_19939
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BACKGROUND
Many studies address anesthesia provider burnout in high-income countries; however, there is a paucity of data on burnout for anesthesia providers in low-income countries (LICs). Our objectives were (1) to evaluate the prevalence of burnout among anesthesia providers in Rwandan hospitals and (2) to determine factors associated with burnout among anesthesia providers in Rwandan hospitals.
METHODS
A questionnaire was sent to selected Rwandan anesthesia providers working in public hospitals. The questionnaire assessed burnout using the Maslach Burnout Inventory Human Services Survey, a validated 22-item survey used to measure burnout among health professionals. Sociodemographic and work-related factors found to be associated with burnout were also assessed using logistic regression in a Bayesian framework to estimate odds ratios (OR) and associated credible intervals (CrIs).
RESULTS
Surveys were distributed to 137 Rwandan anesthesia providers; 99 (72.3%) were returned. Sixty-six (67%) respondents were nonphysician anesthesia providers. Burnout was present in 26 of 99 (26.3%) participants (95% confidence interval [CI], 17.9-36.1). When considering weakly informative priors, we found a 99% probability that not having the right team (OR, 5.36%; 95 CrI, 1.34-23.53) and the frequency of seeing patients with negative outcomes such as death or permanent disability (OR, 9.62; 95% CrI, 2.48-42.84) were associated with burnout.
CONCLUSIONS
In a cross-sectional survey of anesthesia providers in Rwanda, more than a quarter of respondents met the criteria for burnout. Lacking the right team and seeing negative outcomes were associated with higher burnout rate. These identified factors should be addressed to prevent the negative consequences of burnout, such as poor patient outcomes.
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10.1213/ANE.0000000000006053
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pubmed_517_22572
|
We established a simple quantitative PCR procedure with high specificity and sensitivity using TaqMan probes targeting the FOXP2 sequence. This assay distinguished human and nonhuman, including primates, samples with the exception of mouse, turtle, lizard, and fishes. However, the specific amplification of mouse, lizard, and turtle fragments of FOXP2 could be confirmed by electrophoresis after real-time PCR. Because the C(T) values obtained for human DNA were not affected by contaminating animal DNA at concentrations up to 30 times that of human DNA, we were able to estimate the concentration of human DNA in mixed specimens. This assay provides a reliable and useful method for routine quantification of human-specific DNA in forensic practice.
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10.1016/j.fsigen.2011.09.006
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pubmed_407_18311
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PREMISE OF THE STUDY
Climate change may threaten endemic species with extinction, particularly relicts of the Arcto-Tertiary Forest, by elimination of their contemporary habitat. Projections of future habitat are necessary to plan for conservation of these species.
METHODS
We used spline climatic models and modified Random Forests statistical procedures to predict suitable habitats for Brewer spruce (Picea breweriana), which is endemic to the Klamath Region of California and Oregon. We used three general circulation models and two sets of carbon emission scenarios (optimistic and pessimistic) for future climates.
KEY RESULTS
Our procedures predicted present occurrence of Brewer spruce perfectly. For the decades 2030, 2060, and 2090, its projected range within the Klamath Region progressively declined, to the point of disappearance in the decade 2090. The climate niche was projected to move north to British Columbia, the Yukon Territory, and southeastern Alaska.
CONCLUSION
The results emphasize the necessity of assisted colonization and trans-boundary movement to prevent extinction of Brewer spruce. The projections provide a framework for formulating conservation plans, but planners must also consider regulations regarding international plant transfers.
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10.3732/ajb.1200059
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pubmed_672_12280
|
The present study has characterized the short term and long term cultured murine-activated killer (AK) cells that are induced by antibody directed against the epsilon-chain of T3 complex. The conventional lymphokine AK (LAK) cells were generated by culturing normal B6 spleen cells with purified human rIL-2. The alpha T3-induced AK cells (T3AK) were induced by culturing normal B6 spleen cells with alpha T3 and were then maintained in culture medium supplemented with human rIL-2 and/or alpha T3. After initial activation with alpha T3, lymphocyte proliferation and generation of cytotoxic effectors (T3AK) were noted, and these events were related to the endogenous production of IL-2 and IL-4. Addition of alpha IL-2 and/or alpha IL-4 suppressed both the proliferative response and the cytotoxic response induced by alpha T3. In comparing the T3AK cells with the conventional LAK cells, there were many similarities as well as some distinct differences. Both cells displayed a similar cytotoxic spectrum against a variety of tumor targets. The T3AK cells usually gave much higher levels of cytotoxic activity against susceptible targets. However, the susceptibility of different tumor targets to conventional LAK cells and T3AK cells varied. The time course for the generation of lytic activity also differed between the conventional LAK and T3AK cells. One distinct difference was their ability to survive in vitro. The conventional LAK cells survived in culture for only 1 wk. The T3AK cells could survive for at least 4 to 5 wk with active growth. The serologic phenotype of the LAK precursors was asialo GM1 (AsGM1+) cells, but the T3AK precursors could be either AsGM1+ or AsGM1-, depending on the target cell. The LAK effectors were both Lyt-2+ and Lyt-2-, but the short-term T3AK effectors were exclusively Lyt-2+. The long term T3AK cells (cultured for more than 2 wk) were found to consist of Lyt-2+ and Lyt-2- cells, and these subsets of T3AK cells showed different target specificities. These findings demonstrate the heterogeneity of LAK and T3AK cells, and this heterogeneous property may contribute to their diversity in specificity against different tumor targets and thus may affect their effectiveness in the immunotherapy of cancer.
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pubmed_672_12280
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pubmed_146_22413
|
PURPOSE
To assess the value of standard double reading of whole body CT in the management of polytrauma patients.
MATERIALS AND METHODS
Prospective study between January and July 2005. Two senior radiologists with expertise in trauma imaging, blinded to clinical findings, reviewed 105 initial CT examinations of polytrauma patients. These examinations had initially been interpreted by the on-call radiologist. The second interpretations were performed within 12 hours of admission, and were considered the gold standard.
RESULTS
A total of 105 patients were included with 82 males (78%) and 23 females (22%), aged between 2 and 83 years. The level of admission was graded III (n=64), II (n=30) and I (n=11). The second reading identified 3 lesions that were not initially described, each requiring a change in management, including splenic rupture (n=1), thoracic spine fracture (n=1) and epidural hematoma (n=1), with no unfavorable impact on mortality. Additional errors in the initial interpretation were identified: peripheral fractures (n=38), chest (n=36), brain (n=31), abdominal (n=28), spine (n=19) and maxillofacial (17) lesions and contrast extravasation (n=6).
CONCLUSION
Based on the large number and severity of some lesions missed at initial interpretation of whole body CT of polytrauma patients, we recommend standard double reading of these examinations.
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10.1016/s0221-0363(08)93007-9
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pubmed_686_18077
|
UNLABELLED
Resection of musculoskeletal tumors may result in large soft tissue defects that cannot be closed primarily and require prolonged dressing changes and complex surgical interventions for wound coverage. We retrospectively reviewed 23 patients with such defects treated with a vacuum-assisted wound closure system and compared the outcome of these patients with a control group. The study group included 15 women and eight men who had their wounds located at the back (two), pelvic girdle (11), thigh (eight), and leg (two). Treatment included sealed wound coverage with polyurethane foam and overlying tape connected to a vacuum pump. This system was disconnected and changed every 48 hours for 7 to 19 days, after which all defects were reduced in size by an average of 25% and covered with a viable granulation tissue. This allowed primary closure in seven patients, primary closure with skin grafting in 14 patients, and healing by secondary intention in two patients. Compared with the control group, patients in the study group had shorter hospital stays and number of surgical interventions and greater rates of primary wound closure. The use of vacuum-assisted wound closure facilitates wound healing and primary wound closure in patients who have a large soft tissue defect after resection of a musculoskeletal tumor.
LEVEL OF EVIDENCE
Therapeutic study, Level III (retrospective comparative study). See the Guidelines for Authors for a complete description of levels of evidence.
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10.1097/01.blo.0000180450.21350.3e
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pubmed_1048_10176
|
Despite being a common viral disease, influenza has very negative consequences, causing the death of around half a million people each year. A neuraminidase located on the surface of the virus plays an important role in viral reproduction by contributing to the release of viruses from infected host cells. The treatment of influenza is mainly based on the administration of neuraminidase inhibitors. The neuraminidase inhibitors zanamivir, laninamivir, oseltamivir and peramivir have been commercialized and have been demonstrated to be potent influenza viral neuraminidase inhibitors against most influenza strains. In order to create more potent neuraminidase inhibitors and fight against the surge in resistance resulting from naturally-occurring mutations, these anti-influenza drugs have been used as templates for the development of new neuraminidase inhibitors through structure-activity relationship studies. Here, we review the synthetic routes to these commercial drugs, the modifications which have been performed on these structures and the effects of these modifications on their inhibitory activity.
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pubmed_1048_10176
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pubmed_617_20221
|
The field of eating disorders is currently at a crossroads and faces important challenges of sustainability. These challenges include problems with the current diagnostic classification of eating disorders and the divide between scientific research and clinical practice. If not addressed, there is a danger that the field will fail to evolve adaptively, risking increased stagnation and reduced relevance. To meet these challenges, researchers and clinicians must work toward a more holistic ecology of eating disorders based on the interaction of theory, research and practice. The present paper proposes six steps towards increased sustainability based on developing clinically relevant diagnosis, using systematic quality assurance, expanding the scope of treatment research and the definition of evidence, promoting therapist development, as well as stimulating diversity and discourse. If we rise to the occasion and face these challenges, then we will be better equipped to meet the evolving needs of clinicians, researchers, and most importantly patients.
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10.1002/erv.986
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pubmed_403_5383
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In the past decade, there has been remarkable progress in surgical treatment for hepatocellular carcinoma (HCC) based on evidence created by epoch-making prospective trials or national registry big data analysis. A head-to-head randomized controlled trial comparing liver resection and local ablation for small oligo HCCs (SURF trial) demonstrated comparable recurrence-free survival provided both modalities are feasible. Survival benefit of liver resection for HCC with vascular invasion was demonstrated by two propensity scored matched analyses based on Japanese national data. Furthermore, expanded HCC criteria for living donor liver transplantation were developed based on Japanese national data, and this "5-5-500 rule" was accepted by the social insurance system in Japan. The recent remarkable progress in promising new anti-HCC agents may open the door for effective neoadjuvant or adjuvant treatment in combination with surgery.
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10.35772/ghm.2020.01086
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pubmed_45_2630
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Depression induced cognitive impairment, also referred to as the dementia syndrome of depression or pseudodementia, has been well characterized, yet the extent to which the more common mild depressive symptoms influence cognition has not been well studied. We sought to identify the influence of mild depressive symptoms on verbal fluency performance in a large sample of healthy community dwelling older adults. Letter and semantic fluency testing was conducted on 188 participants (ages 60-92 years) with no known history of neurologic or psychiatric disease. Depressive symptoms were assessed with the Geriatric Depression Scale (GDS). A total of 39 subjects obtained GDS scores consistent with mild depressive symptoms (GDS=10-19), and 149 subjects were identified as not depressed (GDS<10). ANOVA indicated that subjects with mild depressive symptoms performed significantly worse than normal controls on letter fluency (p<.05), but there was no significant difference between the groups on semantic fluency. Analysis of the nondepressed group stratified into young-old, middle-old, and oldest-old revealed a significant decline in semantic (p<.001) but not letter fluency with age. The nondepressed young-old showed the expected advantage for word list generation to semantic as compared to letter categories, yet this pattern was reversed in the older age groups, where letter fluency scores exceeded semantic fluency scores. Our results suggest that the presence of even mild depressive symptoms may confound using letter versus category discrepancies in the differential diagnosis of dementia. Further, our findings suggest that the commonly used strategy of examining letter-semantic fluency discrepancies may not be relevant for individuals of advanced age. Age-stratified normative data for fluency testing in older adults is also provided.
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10.1076/clin.17.2.195.16500
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pubmed_41_22474
|
PURPOSE
The aim of this study was to model impacted maxillary canines and determine whether areas of ankylosis were present before undertaking orthodontic traction.
MATERIAL AND METHODS
Amira/ResolveRT™ software, version 5.0, by FEI Company is a meshing and surface-rendering program that was used to produce three-dimensional reconstructions from CT scans and cone beam images of the impacted canines of 30 patients (10 cone beam files and 20 CT scan files).
RESULTS AND DISCUSSION
The presence of zones of ankylosis on the roots of certain impacted canines is revealed by the inversion of the direction of meshing on the tooth surface and on a larger scale by invagination of bone tissue into the tooth tissue at various densities measured in Hounsfield units by the AMIRA™ software program. This observation can guide treatment towards extraction of the impacted tooth, its autotransplantation, or deep alveolar corticotomy, followed by mobilization when the canine is in a vestibular position.
CONCLUSION
AMIRA™ software made it possible to detect zones of ankylosis on the roots of certain impacted canines and to adopt a treatment program different from conventional surgico-orthodontic traction. The final aim is to reposition the impacted canine without endangering the adjacent teeth.
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10.1016/j.ortho.2017.09.009
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pubmed_162_17603
|
When a child presents with high-anion gap metabolic acidosis, the pediatrician can proceed with confidence by recalling some basic principles. Defects of organic acid, pyruvate, and ketone body metabolism that present with acute acidosis are reviewed. Flowcharts for identifying the underlying cause and initiating life-saving therapy are provided. By evaluating electrolytes, blood sugar, lactate, ammonia, and urine ketones, the provider can determine the likelihood of an inborn error of metabolism. Freezing serum, plasma, and urine samples during the acute presentation for definitive diagnostic testing at the provider's convenience aids in the differential diagnosis.
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10.1016/j.pcl.2017.11.003
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pubmed_765_1785
|
Since the outbreak of COVID-19 in China in December 2019, a pandemic has rapidly developed on a scale that has overwhelmed health services in a number of countries. COVID-19 has the potential to lead to severe hypoxia; this is usually the cause of death if it occurs. In a substantial number of patients, adequate arterial oxygenation cannot be achieved with supplementary oxygen therapy alone. To date, there has been no clear guideline endorsement of ward-based non-invasive pressure support (NIPS) for severely hypoxic patients who are deemed unlikely to benefit from invasive ventilation. We established a ward-based NIPS service for COVID-19 PCR-positive patients, with severe hypoxia, and in whom escalation to critical care for invasive ventilation was not deemed appropriate. A retrospective analysis of survival in these patients was undertaken. Twenty-eight patients were included. Ward-based NIPS for severe hypoxia was associated with a 50% survival in this cohort. This compares favourably with Intensive Care National Audit and Research Centre survival data following invasive ventilation in a less frail, less comorbid and younger population. These results suggest that ward-based NIPS should be considered as a treatment option in an integrated escalation strategy in all units managing respiratory failure secondary to COVID-19.
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10.1136/bmjresp-2020-000621
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pubmed_698_10951
|
The reaction of iron(III) (meso-tetrakis(N-methylpyridinium-4-yl)porphyrin (Fe(III)TMPyP) with nitric oxide (NO) was studied by electronic absorption spectroscopy, ESR, and electrochemical and spectroelectrochemical techniques in aqueous solutions with pH from 2.2 to 12.0. Fe(III)TMPyP has been found to undergo a reductive nitrosylation in all pHs, and the product of nitric oxide binding to the porphyrin has been determined as iron(II) porphyrin nitrosyl complex ([Fe(II)(NO)TMPyP]). The rate of the reductive nitrosylation exhibits a tendency to get faster with increase in pH. An intermediate species was observed around neutral pH by spectroelectrochemical technique and was proposed to be the iron(II) nitrosyl complex of the mu-oxo dimeric form of FeTMPyP, which is known to be a predominant in neutral solutions.
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10.1021/ic025830n
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pubmed_918_1958
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The levodopa carbidopa intestinal gel is a device-assisted therapy used for the management of fluctuating motor symptoms of Parkinson's disease that are refractory to oral therapy. The approach has demonstrable clinical value, but consideration of the associated need for expert care, access to services, and costs of the treatment impact the method of introduction to optimize uptake and minimize discontinuation across populations examined. Systematic approaches and modifications have been explored by different centers over the years to mitigate these considerations, with the aim of minimizing adverse events and maximizing the quality-of-life years gained with the treatment. In this presentation, we aim to outline an approach to managing this treatment while highlighting measures that can be utilized throughout the process to improve patients' experiences.
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10.1002/mdc3.12701
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pubmed_1013_20639
|
Chondrina Reichenbach, 1828 is a highly diverse genus of terrestrial molluscs currently including 44 species with about 28 subspecific taxa. It is distributed through North Africa, central and southern Europe, from Portugal in the West to the Caucasus and Asia Minor in the East. Approximately 70% of the species are endemic to the Iberian Peninsula constituting its main center of speciation with 34 species. This genus includes many microendemic taxa, some of them not yet described, confined to limestone habitats (being strictly rock-dwelling species). They are distributed on rocky outcrops up to 2000 m.a.s.l. It is a genus of conical-fusiform snails that differ mainly in shell characters and in the number and position of teeth in their aperture. So far, molecular studies on Chondrina have been based exclusively on the mitochondrial Cytochrome Oxidase subunit I region (COI). These studies gave a first view of the phylogeny of the genus but many inner nodes were not statistically supported. The main objective of the study is to obtain a better understanding of the phylogeny and systematics of the genus Chondrina on the Iberian Peninsula, using multilocus molecular analysis. Partial sequences of the COI and 16S rRNA genes, as well as of the nuclear Internal Transcribed Spacer 1 (ITS1-5.8S) and Internal Transcribed Spacer 2 (5.8S-ITS2-28S) were obtained from individuals of all the extant Chondrina species known from the Iberian Peninsula. In addition to this, the newly obtained COI sequences were combined with those previously published in the GenBank. Phylogenetic relationships were inferred using maximum likelihood and Bayesian methods. The reconstructed phylogenies showed high values of support for more recent branches and basal nodes. Moreover, molecular species delimitation allowed to better definethe studied species and check the presence of new taxa.
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10.1016/j.ympev.2022.107480
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pubmed_1027_17414
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A cDNA encoding a two-domain hemoglobin (Hb) chain of Daphnia magna was cloned and its nucleotide (nt) sequence of 1261 bp was determined. The nt sequence contained 74 bp of the leader sequence, 1047 bp of an open reading frame (ORF), and 119 bp of the 3'-untranslated region (UTR), excluding the polyadenylation tail. A sequence, AATACA, located 24 bp upstream from the polyA sequence was considered to be a polyadenylation signal. cDNA-derived amino acid (aa) sequence revealed that D. magna Hb chain is synthesized as a secretory precursor with a signal peptide of 18 aa. Mature D. magna Hb chain consists of 330-aa residues with a calculated molecular weight of 36227, which is composed of two large repeated domains, domain 1 and 2. Several key aa that are invariant in all or most of other Hb and required for functional heme-binding are conserved in each of the two domains. The N-terminal extension (pre-A segment) of domain 1 was unusually long and contained an unusual threonine-rich sequence. The homology between the aa sequences of the two domains (24% identity) was much lower than that observed in other two-domain Hb chains from clams or nematode. Hb mRNA level in D. magna reared under low oxygen concentration was more than 12 times higher than that in D. magna reared with sufficient aeration, indicating that the expression of Hb gene is regulated by mRNA level.
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10.1016/s0378-1119(96)00836-0
|
pubmed_222_15799
|
Intentional trauma has become a significant threat to the health and well-being of all American children. Clinical management of a critically injured child represents a distinctive challenge for the pediatric trauma team. The critical care nurse is an integral part of this team and plays a vital role in the ongoing assessment and management of this unique population. This article presents the patterns of nonaccidental injuries in children and provides strategies for nursing practice in the critical care environment.
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pubmed_222_15799
|
pubmed_827_15964
|
Individuals with tuberous sclerosis complex (TSC) exhibit a variety of neurologic abnormalities, including mental retardation, epilepsy, and autism. Examination of human TSC brains demonstrate dysplastic astrocytes and neurons, areas of abnormal neuronal migration (tubers), and hamartomatous growths, termed subependymal nodules, which can progress to subependymal giant cell astrocytomas (SEGA). Previous studies have suggested that these neuropathologic features may result from abnormal neuroglial cell differentiation. In an effort to provide support for this hypothesis and to identify specific markers of aberrant neuroglial cell differentiation in TSC, we employed gene expression profiling on Tsc1 conditional knockout (Tsc1(GFAP)CKO) mouse astrocytes. We identified several transcripts implicated in central nervous system development that are differentially expressed in Tsc1(-/-) astrocytes compared to wild-type astrocytes. We validated the differential expression of select transcripts on the protein level both in primary cultures of Tsc1(-/-) astrocytes and in Tsc1(GFAP)CKO mouse brains. Moreover, we show that these markers are also differentially expressed within cortical tubers, but not in adjacent normal tissue from TSC patient brains. This study provides supportive evidence for a developmental defect in neuroglial cell differentiation relevant to the genesis of TSC nervous system pathology and underscores the utility of mouse modeling for understanding the molecular pathogenesis of human disease.
|
10.1002/glia.10324
|
pubmed_245_19304
|
BD Phoenix™ is an automated bacterial identification and susceptibility testing system. Here, its performance in screening IMP-producing Enterobacteriaceae was evaluated. The system identified 97.8% of IMP producers as being nonsusceptible to imipenem or meropenem, which was higher than that identified by the broth microdilution method (91.3%, imipenem; 41.3%, meropenem).
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10.1016/j.mimet.2017.12.006
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pubmed_989_16090
|
Pandemics require a fast and immediate response to contain potential infectious carriers. In the recent 2020 Covid-19 worldwide pandemic, authorities all around the world have failed to identify potential carriers and contain it on time. Hence, a rapid and very sensitive testing method is required. Current diagnostic tools, reverse transcription PCR (RT-PCR) and real-time PCR (qPCR), have its pitfalls for quick pandemic containment such as the requirement for specialized professionals and instrumentation. Versatile electrochemical DNA/RNA sensors are a promising technological alternative for PCR based diagnosis. In an electrochemical DNA sensor, a nucleic acid hybridization event is converted into a quantifiable electrochemical signal. A critical challenge of electrochemical DNA sensors is sensitive detection of a low copy number of DNA/RNA in samples such as is the case for early onset of a disease. Signal amplification approaches are an important tool to overcome this sensitivity issue. In this review, the authors discuss the most recent signal amplification strategies employed in the electrochemical DNA/RNA diagnosis of pathogens.
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10.3390/s20164648
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pubmed_344_2099
|
This study investigated the effect of sildenafil citrate on micro-recanalization and neovascularization, which were previously demonstrated in a rat model using biodegradable grafts (BGs) for vas deferens reconstruction. A total of 24 male rats underwent bilateral vasectomy with removal of a 0.5-cm vasal segment and were randomly assigned to four groups. Groups 1 and 2 underwent immediate vasovasostomy. Groups 3 and 4 underwent interposition of a 0.5-cm BG in the vasal gap. Groups 1 and 3 were given 5 mg kg(-1) day(-1) oral sildenafil. Other groups were given placebo. Rats were housed with females 12 weeks postoperatively. Reconstructed vasal segments were harvested 16 weeks postoperatively and analyzed histologically. Fluid from the distal vasal stump was analyzed for motile sperm. Urine samples obtained 16 weeks postoperatively were analyzed for cGMP levels. cGMP levels in rats treated with sildenafil were significantly higher than in control rats. No pregnancies were sired by grafted groups. In all, 5/6 rats in group 1 and 3/6 rats in group 2 sired litters. No motile sperm were noted in the vasal fluid of the grafted groups. Motile sperm were noted in all rats in group 1 and in 5/6 rats in group 2. In addition, 29 and 4 microcanals were detected in the sildenafil and placebo groups, respectively (P = 0.023). No microcanal exceeded 3 mm in length. An average of 12 and 28 blood vessels per graft were noted in the placebo and sildenafil groups, respectively (P < 0.0001). In conclusion, sildenafil enhances micro-recanalization and neovascularization in BG used for vas deferens reconstruction, but does not increase the microcanal length after 16 weeks.
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10.1038/aja.2010.55
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pubmed_886_14687
|
Glucotoxicity contributes to beta-cell dysfunction through oxidative stress. Our previous study demonstrated that tualang honey ameliorated renal oxidative stress and produced hypoglycemic effect in streptozotocin (STZ)-induced diabetic rats. This present study investigated the hypothesis that hypoglycemic effect of tualang honey might partly be due to protection of pancreas against oxidative stress. Diabetes was induced by a single dose of STZ (60 mg/kg; ip). Diabetic rats were randomly divided into two groups and administered distilled water (0.5 ml/d) and tualang honey (1.0 g/kg/d). Similarly, two groups of non-diabetic rats received distilled water (0.5 ml/d) and tualang honey (1.0 g/kg/d). The animals were treated orally for 28 days. At the end of the treatment period, the honey-treated diabetic rats had significantly (p<0.05) reduced blood glucose levels [8.8 (5.8)mmol/L; median (interquartile range)] compared with the diabetic control rats [17.9 (2.6)mmol/L]. The pancreas of diabetic control rats showed significantly increased levels of malondialdehyde (MDA) and up-regulation of superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities. Catalase (CAT) activity was significantly reduced while glutathione-S-transferase (GST) and glutathione reductase (GR) activities remained unchanged in the pancreas of diabetic rats. Tualang honey significantly (p<0.05) reduced elevated MDA levels. Honey treatment also restored SOD and CAT activities. These results suggest that hypoglycemic effect of tualang honey might be attributed to its antioxidative effect on the pancreas.
|
10.1016/j.ando.2010.03.003
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pubmed_325_2296
|
The postpartum period is a window of risk for psychological disturbances and particularly for depressive symptoms. This study explored the relationships between postpartum depression and prepartum depressive symptoms, marital adjustment, support from family, previous depressive symptomology, and pregnancy planning. A total of 128 women who were receiving prenatal care at a state hospital in Istanbul, Turkey, and who were in the last trimester of their pregnancy participated in the first phase of the study. Of these, eighty-seven women also participated in the second phase, during the 3-6 month postpartum period. The results indicated that depressed mood in the last trimester of pregnancy, family support, care and support from spouse, previous depression history, and unplanned pregnancy were significant risk factors for postpartum depressive symptoms; significant differences were found for study variables as a function of women's scores on the Edinburgh Postnatal Depression Scale in pregnancy and in the postpartum period. The recommendation is made to use screening tools, like the Edinburgh Postnatal Depression Scale, in the course of routine prenatal care, and to refer women with Edinburgh Postnatal Depression Scale scores above the cutoff score for further clinical examination.
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10.1080/03630242.2015.1101737
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pubmed_128_20496
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As an important content of alternative and complementary medicine, acupuncture therapy has been proved to be effective in relieving myocardial ischemia (MI). Authors of the present paper review recent progress of researches on acupuncture therapy in resisting MI from 1) improving cardiovascular function and promoting angiogenesis, and 2) protecting myocardial cells from further injury and reducing cellular apoptosis at different pathological stages of MI. Moreover, the authors discuss the characteristics of epigenetic regulation in the process of MI and cardiac repair including the methylating of DNA, modification of histone, remodeling of the chromatin, and micro-RNA expression, mediating cellular apoptosis, regeneration of myocardial blood vessels, etc. The authors hold that future studies on the underlying mechanisms of acupuncture therapy in the prevention and treatment of MI from epigenetics may be a new approach and a new direction.
|
pubmed_128_20496
|
pubmed_386_4612
|
A study of ailments of the feet in pilgrims of Hajj revealed that 31% of them suffered from blisters, and the prevalence was five times higher in females. The presence of comorbidity (diabetes, obesity and advanced age) warrants immediate attention to them to avoid serious complications.
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pubmed_386_4612
|
pubmed_931_10592
|
Because acute cholangitis sometimes rapidly progresses to a severe form accompanied by organ dysfunction, caused by the systemic inflammatory response syndrome (SIRS) and/or sepsis, prompt diagnosis and severity assessment are necessary for appropriate management, including intensive care with organ support and urgent biliary drainage in addition to medical treatment. However, because there have been no standard criteria for the diagnosis and severity assessment of acute cholangitis, practical clinical guidelines have never been established. The aim of this part of the Tokyo Guidelines is to propose new criteria for the diagnosis and severity assessment of acute cholangitis based on a systematic review of the literature and the consensus of experts reached at the International Consensus Meeting held in Tokyo 2006. Acute cholangitis can be diagnosed if the clinical manifestations of Charcot's triad, i.e., fever and/or chills, abdominal pain (right upper quadrant or epigastric), and jaundice are present. When not all of the components of the triad are present, then a definite diagnosis can be made if laboratory data and imaging findings supporting the evidence of inflammation and biliary obstruction are obtained. The severity of acute cholangitis can be classified into three grades, mild (grade I), moderate (grade II), and severe (grade III), on the basis of two clinical factors, the onset of organ dysfunction and the response to the initial medical treatment. "Severe (grade III)" acute cholangitis is defined as acute cholangitis accompanied by at least one new-onset organ dysfunction. "Moderate (grade II)" acute cholangitis is defined as acute cholangitis that is unaccompanied by organ dysfunction, but that does not respond to the initial medical treatment, with the clinical manifestations and/or laboratory data not improved. "Mild (grade I)" acute cholangitis is defined as acute cholangitis that responds to the initial medical treatment, with the clinical findings improved.
|
10.1007/s00534-006-1156-7
|
pubmed_5_21333
|
Behavioral and neuroendocrine responses underlying systemic osmoregulation are synergistically controlled by osmoreceptors and neuropeptides released within the hypothalamus. Although mechanisms underlying osmoreception are understood, the cellular basis for the integration of osmotic and peptidergic signals remains unknown. Here we show that the excitatory effects of angiotensin II, cholecystokinin and neurotensin on supraoptic neurosecretory neurons are due to the stimulation of the stretch-inactivated cation channels responsible for osmoreception. This molecular convergence underlies the facilitatory effects of neuropeptides on responses to osmotic stimulation and provides a basis for the gating effects of plasma osmolality on the responsiveness of osmoregulatory neurons to peptidergic stimulation.
|
10.1038/75744
|
pubmed_437_10680
|
Human phosphatase and tensin homolog (hPTEN) gene was expressed in vascular smooth muscle cells (VSMCs) to study its effect on VSMC proliferation induced in platelet-derived growth factor (PDGF) conditioned medium. After G418 selection, MTT assay was conducted to examine transfected VSMC proliferation induced in human PDGF conditioned medium. We successfully constructed eukaryotic expression vector pcDNA4/myc-His-PTEN and transferred into VSMC cells. We report that in vitro proliferation of VSMC was inhibited in PTEN transfected VSMCs induced in PDGF conditioned medium. RT-PCR and Western blot results indicated significantly high levels of protein kinase B-PKB and nuclear factor kappa B mRNA and protein, respectively, in PDGF group as compared with the control group.
|
10.1007/s12013-014-0039-9
|
pubmed_658_6323
|
We report the physiological role of OhrR as an organic peroxide sensor and transcription repressor in Xanthomonas campestris pv. phaseoli. In vivo exposure of X. campestris pv. phaseoli to either tert-butyl or cumene hydroperoxides efficiently neutralized OhrR repression of expression from the OhrR-regulated P1 promoter. H2O2 was a weak and non-physiological inducer of the system while other oxidants and metabolites of organic peroxide metabolism did not induce the expression from the P1. Northern blotting results indicated a correlation between concentrations of tert-butyl hydroperoxide used in the treatment and the induction of ohr (an OhrR-regulated gene) expression. In addition, the levels of ohr mRNA in cultures induced by various concentrations of tert-butyl hydroperoxide were reduced in cells with high levels of an organic peroxide metabolising enzyme (AhpC-AhpF) but not in cells with high catalase levels suggesting that organic peroxide interacts with OhrR. DNA band shift experiments using purified OhrR and the P1 promoter fragment showed that organic peroxide treatment prevented binding of the protein to the P1 promoter by oxidation of OhrR, as the inhibition of binding to the P1 promoter was reversed by addition of a reducing agent, DTT. The highly conserved cysteine residue C22 of OhrR is required for organic peroxide inducible gene expression. A mutant protein, OhrRC22S can repress the P1 promoter activity but is insensitive to organic peroxide treatment. Thus, OhrR is the first transcription repressor characterized that appeared to evolve to physiologically sense organic peroxides.
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10.1046/j.1365-2958.2002.03116.x
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pubmed_893_10120
|
OBJECTIVES
We evaluated the benefits of adding high-fidelity simulation to a teenage trauma prevention program to decrease recidivism rates and encourage teens to discuss actionable steps toward safe driving.
METHODS
A simulated pediatric trauma scenario was integrated into an established trauma prevention program. Participants were recruited because they were court-ordered to attend this program after misdemeanor convictions for moving violations. The teenage participants viewed this simulation from the emergency medical services (EMS) handoff to complete trauma care. Participants completed a postsimulation knowledge assessment and care evaluation, which included narrative data about the experience. Qualitative analysis of color-coded responses identified common themes and experiences in participants' answers. Court records were reviewed 6 years after course completion to determine short- and long-term recidivism rates, which were then compared to our program's historical rate.
RESULTS
One hundred twenty-four students aged 16-20 years participated over a 2-year study period. Narrative responses included general reflection, impressions, and thoughts about what they might change as a result of the course. Participants reported that they would decrease speed (30%), wear seat belts (15%), decrease cell phone use (11%), and increase caution (28%). The recidivism rate was 55% within 6 years. At 6 months it was 8.4%, at 1 year it was 20%, and it increased approximately 5-8% per year after the first year. Compared with our programs, for historical 6-month and 2-year recidivism rates, no significant difference was seen with or without simulation.
CONCLUSIONS
Adding simulation is well received by participants and leads to positive reflections regarding changes in risk-taking behaviors but resulted in no changes to the high recidivism rates This may be due to the often ineffectiveness of fear appeals.
|
10.1080/15389588.2017.1407925
|
pubmed_1092_7326
|
INTRODUCTION
The aim of this study was to test the clinimetric properties of the Comprehensive Cervical Dystonia Rating Scale. This is a modular scale with modifications of the Toronto Western Spasmodic Torticollis Rating Scale (composed of three subscales assessing motor severity, disability, and pain) now referred to as the revised Toronto Western Spasmodic Torticollis Scale-2; a newly developed psychiatric screening instrument; and the Cervical Dystonia Impact Profile-58 as a quality of life measure.
METHODS
Ten dystonia experts rated subjects with cervical dystonia using the comprehensive scale. Clinimetric techniques assessed each module of the scale for reliability, item correlation, and factor structure.
RESULTS
There were 208 cervical dystonia patients (73% women; age, 59 ± 10 years; duration, 15 ± 12 years). Internal consistency of the motor severity subscale was acceptable (Cronbach's alpha = 0.57). Item to total correlations showed that elimination of items with low correlations (<0.20) increased alpha to 0.71. Internal consistency estimates for the subscales for disability and pain were 0.88 and 0.95, respectively. The psychiatric screening scale had a Cronbach's alpha of 0.84 and satisfactory item to total correlations. When the subscales of the Toronto Western Spasmodic Torticollis Scale-2 were combined with the psychiatric screening scale, Cronbach's alpha was 0.88, and construct validity assessment demonstrated four rational factors: motor; disability; pain; and psychiatric disorders. The Cervical Dystonia Impact Profile-58 had an alpha of 0.98 and its construction was validated through a confirmatory factor analysis.
CONCLUSIONS
The modules of the Comprehensive Cervical Dystonia Rating Scale are internally consistent with a logical factor structure.
|
10.1002/mds.26534
|
pubmed_242_17795
|
In metastatic castration-resistant prostate cancer (mCRPC) clinical trials, the assessment of treatment efficacy essentially relies on the time to death and the kinetics of prostate-specific antigen (PSA). Joint modeling has been increasingly used to characterize the relationship between a time to event and a biomarker kinetics, but numerical difficulties often limit this approach to linear models. Here, we evaluated by simulation the capability of a new feature of the Stochastic Approximation Expectation-Maximization algorithm in Monolix to estimate the parameters of a joint model where PSA kinetics was defined by a mechanistic nonlinear mixed-effect model. The design of the study and the parameter values were inspired from one arm of a clinical trial. Increasingly high levels of association between PSA and survival were considered, and results were compared with those found using two simplified alternatives to joint model, a two-stage and a joint sequential model. We found that joint model allowed for a precise estimation of all longitudinal and survival parameters. In particular, the effect of PSA kinetics on survival could be precisely estimated, regardless of the strength of the association. In contrast, both simplified approaches led to bias on longitudinal parameters, and two-stage model systematically underestimated the effect of PSA kinetics on survival. In summary, we showed that joint model can be used to characterize the relationship between a nonlinear kinetics and survival. This opens the way for the use of more complex and physiological models to improve treatment evaluation and prediction in oncology.
|
10.1208/s12248-015-9745-5
|
pubmed_390_3440
|
A case of P. aeruginosa septicaemia originating from a pace-maker electrode is described. Cure was obtained by surgical ablation of the contaminated electrode by a right thoracotomy and monotherapy with cefsulodin, an antibacterial agent. Nephrotoxicity was observed during treatment and regressed after its withdrawal. No other potentially nephrotoxic drug was used. The therapeutic indications of new beta-lactamase stable cephalosporins are reviewed.
|
pubmed_390_3440
|
pubmed_689_1232
|
An observational study was conducted in Ukraine to determine the independent mortality risks among adult inpatients with COVID-19. The results of treatment of COVID-19 inpatients (n = 367) are presented, and waist circumference (WC) was measured. Logistic regression analysis was applied to evaluate the effects of factors on the risk of mortality. Odds ratios and 95% CIs for the association were calculated. One hundred and three of 367 subjects had fasting plasma glucose level that met the diabetes mellitus criteria (≥7.0 mmol/L), in 53 patients, diabetes mellitus was previously known. Two hundred and eleven patients did not have diabetes or hyperglycemia. Diabetes mellitus/hyperglycemia odds ratio 2.5 (CI 1.0-6.1), p = 0.045 loses statistical significance after standardization by age, waist circumference or fasting plasma glucose. No effect on gender, body mass index-determined obesity, or hypertension was found. The fasting plasma glucose (>8.5 mmol/L), age (≥61 years), and waist circumference (>105 cm) categories were associated with ORs 6.34 (CI 2.60-15.4); 4.12 (CI 1.37-12.4); 8.93 (CI 3.26-24.5), respectively. The optimal model of mortality risk with AUC 0.86 (CI 0.81-0.91) included the diabetes/heperglycemia and age categories as well as waist circumference as a continued variable. Waist circumference is an independent risk factor for mortality of inpatients with COVID-19.
|
10.1177/15353702211054452
|
pubmed_805_17991
|
An AIDS patient with severe large volume diarrhea and malnutrition due to cryptosporidial infection is presented. The patient, who was not receiving zidovudine, was treated with octreotide with resolution of diarrhea leading to improvement in nutritional status, immune functions, and subsequently, resolution of the Cryptosporidium infection. This case points out the need for adequate nutrition in AIDS patients and highlights the relationship of nutrition and the immune system.
|
pubmed_805_17991
|
pubmed_246_4778
|
Although there is little evidence in the literature, it is widely believed that congenital hydrocephalus is only very rarely associated with papilloedema. This study, conducted on 200 consecutive cases (including 35 of secondary hydrocephalus), is probably the first report in the literature of optic nerve changes in a large series, and papilloedema in congenital hydrocephalus does not seem to be so uncommon after all. The importance of its early diagnosis, almost entirely dependent in children on objective features, cannot be over-emphasized in the management of hydrocephalus. Analysis of a few ophthalmoscopic signs in these eyes with papilloedema showed that presence or absence of the spontaneous or induced venous pulsations per se does not decide the diagnosis. The presence of venous engorgement seems to be a more definite and reliable indicator of early papilloedema.
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pubmed_246_4778
|
pubmed_377_21291
|
PURPOSE
To elicit South African medical students' experiences of witnessing patient rights abuses and professional lapses during their clinical training in order to inform an appropriate and effective response.
METHOD
During June and July 2009 at the University of Cape Town Faculty of Health Sciences, the authors surveyed 223 fourth-, fifth-, and sixth-year medical students in selected clinical rotations concerning abuses they had observed. Volunteers were later interviewed individually. The authors coded interview transcripts for key themes using a constant-comparative grounded theory approach.
RESULTS
Of 223 students surveyed, 183 (82%) responded, 130 (71%) of whom reported witnessing patient rights abuses and professional lapses, including physical abuse (38%), verbal abuse (37%), disrespect for patients' dignity (25%), and inadequately informing patients about their treatment (25%). Students attributed abuse to stressed health workers, overburdened facilities, and disempowered patients. Most students who witnessed abuse (59%) did not actively respond, and 64% of survey respondents felt unprepared or uncertain about challenging abuses in the future. Interviews with 28 students yielded detailed accounts of the abuses witnessed and of students' emotional reactions, coping strategies, and responses. Most students did not report abuses; they feared reprisal or doubted it would make a difference.
CONCLUSIONS
This study demonstrates the disjunction between what these students were taught about human rights and ethics and what they witnessed in clinical settings. The high prevalence of patient rights abuses experienced by these students highlights the need to align medical ethics and human rights with medico-legal protocols in theory and clinical practice.
|
10.1097/ACM.0b013e31822be4b8
|
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