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pubmed_449_10752
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The effect of methotrexate (MTX) on the growth and human chorionic gonadotropin (hCG) secretion of five gestational and two nongestational human choriocarcinoma cell lines was studied in vitro. A striking heterogeneity in hCG secretion was noted among the cell lines. The growth of cells which secreted large quantities of hCG, such as HCCM-5, BeWo, and IMa, was inhibited by continuous exposure to 2 X 10(-8)M MTX. In contrast, cells which secreted little hCG, such as SCH, ENAMI-1, and GCH-1, showed no response to the growth inhibitory action of 2 X 10(-8)M MTX and the 3H-thymidine uptake was not reduced by treatment with MTX at doses of up to 10(-4)M for 48 hours. The common morphologic alterations observed in the cells which responded to MTX were an increase in the number of multinucleated giant cells, the appearance of vacuoles and granules in the cytoplasm, and enlargement of the nuclei. Increased hCG secretion was observed in accordance with the appearance of such morphologically altered cells. Part of the mechanisms of resistance to MTX appeared to involve both impairment of MTX uptake by the cells and an increase in the level of intracellular dihydrofolate reductase.
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10.1016/0002-9378(83)90927-4
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pubmed_1012_11703
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OBJECTIVES
This study was aimed at exploring the conflicts and ethical problems experienced by professionals involved in prenatal diagnosis and termination of pregnancy (TOP) in order to improve the understanding of decision-making processes and medical practices in the field of prenatal diagnosis.
METHODS
Qualitative study with in-depth tape-recorded interviews conducted in three tertiary care maternity units in France, between May 1999 and March 2000. All full-time obstetricians and half of the full-time midwives were contacted. Seventeen obstetricians and 30 midwives participated (three refusals, five missing). Interviews were transcribed and analysed successively by two different researchers.
RESULTS
All respondents stated that prenatal diagnosis and TOP raised important ethical dilemmas, the most frequent being request for abortion in case of minor anomalies. They pointed out the inability of our society to appropriately care for disabled children and the risk of eugenic pressures. The decisions and practices in prenatal diagnosis should be debated throughout society. All respondents reported that their unit did not have protocols for deciding when a TOP was justifiable. The transmission of information to the women appeared to be a problematic area. Moral conflicts and emotional distress were frequently expressed, especially by midwives who mentioned the need for more discussions and support groups in their department.
CONCLUSION
Health professionals involved in prenatal diagnosis face complex ethical dilemmas which raise important personal conflicts. A need for more resources for counselling women and for open debate about the consequences of the current practices clearly emerged.
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10.1002/pd.427
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pubmed_766_127
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The ankle is the site of frequent athletic injuries, the most significant of which include Achilles' rupture, peroneal tendon dislocation, and lateral ligamentous rupture. Evaluation techniques and treatment methods stressing an early but graduated return to function are discussed for the major soft tissue injuries of the ankle.
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pubmed_766_127
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pubmed_181_3115
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Two new conjugated acceptor-π-donor-π-acceptor (A-π-D-π-A) porphyrins have been synthesised using 3-ethylrhodanine (1a) or dicyanovinylene (1b) groups as acceptor units. Their optical and electrochemical properties made these materials excellent electron donors along with PC71BM as the acceptor for solution-processed bulk heterojunction organic solar cells. The devices based on 1a:PC71BM (1 : 2) and 1b:PC71BM (1 : 2) processed with CB showed low power conversion efficiencies (PCE) of 2.30% and 2.80%, respectively. Nonetheless, after processing the active layer using a mixture of 3 vol% of a pyridine additive in THF, the PCE was enhanced up to 5.14% and 6.06% for 1a:PC71BM and 1b:PC71BM, respectively. Moreover, when we used LiTFSI as the chemical additive in pyridine/CB-processed 1b:PC71BM an excellent PCE of 7.63% was recorded. The effects over the film morphology and the device characteristics (Jsc, Voc and FF) due to the introduction of LiTFSI are discussed.
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10.1039/c6nr06374h
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pubmed_219_5960
|
Patient data report marked gender and pre-vs-postmenopausal differences in obstructive sleep apnea (OSA). However, no experimental data are available on how sexual hormones modulate OSA consequences. Here we report novel results on estrogen-modulated heart and brain inflammation in female mice subjected to intermittent hypoxia, a major injurious challenge in OSA. C57BL/6J (14-week old) intact and ovariectomized mice (n=6 each) were subjected to intermittent hypoxia (20 s at 5% and 40s at 21%, 60 cycles/h; 6 h/day). Identical intact and ovariectomized groups breathing room air were controls. After 30 days, the gene expressions of interleukins 6 and 8 (IL-6, IL-8) in the brain and heart tissues were measured. Whereas, compared with normoxia, intermittent hypoxia considerably increased IL-6 and IL-8 gene expressions in intact females, no change was found in ovariectomized mice when comparing normoxia and intermittent hypoxia. These data suggest that estrogens modulate the inflammatory effects of intermittent hypoxia and point to further studies on the role played by sex hormones in OSA.
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pubmed_219_5960
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pubmed_801_14603
|
The Mental Attributes Profiling System was developed in 2002 (Laouris and Makris, Proceedings of multilingual & cross-cultural perspectives on Dyslexia, Omni Shoreham Hotel, Washington, D.C, 2002), to provide a multimodal evaluation of the learning potential and abilities of young children's brains. The method is based on the assessment of non-verbal abilities using video-like interfaces and was compared to more established methodologies in (Papadopoulos, Laouris, Makris, Proceedings of IDA 54th annual conference, San Diego, 2003), such as the Wechsler Intelligence Scale for Children (Watkins et al., Psychol Sch 34(4):309-319, 1997). To do so, various tests have been applied to a population of 134 children aged 7-12 years old. This paper addresses the issue of identifying a minimal set of variables that are able to accurately predict the learning abilities of a given child. The use of Machine Learning technologies to do this provides the advantage of making no prior assumptions about the nature of the data and eliminating natural bias associated with data processing carried out by humans. Kohonen's Self Organising Maps (Kohonen, Biol Cybern 43:59-69, 1982) algorithm is able to split a population into groups based on large and complex sets of observations. Once the population is split, the individual groups can then be probed for their defining characteristics providing insight into the rationale of the split. The characteristics identified form the basis of classification systems that are able to accurately predict which group an individual will belong to, using only a small subset of the tests available. The specifics of this methodology are detailed herein, and the resulting classification systems provide an effective tool to prognose the learning abilities of new subjects.
|
10.1007/s12559-010-9052-5
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pubmed_829_8533
|
The hypothalamus integrates various hormonal and neuronal signals to regulate appetite and metabolism and thereby serves a homeostatic purpose in the regulation of body weight. Additional neural circuits that are superimposed on this system have the potential to override the homeostatic signals, resulting in either gluttony or anorexia at the extremes. Midbrain dopamine neurons have long been implicated in mediating reward behavior and the motivational aspects of feeding behavior. Recent results reveal that hormones implicated in regulating the homeostatic system also impinge directly on dopamine neurons; for example, leptin and insulin directly inhibit dopamine neurons, whereas ghrelin activates them. Here, I discuss the predictions and implications of these new findings as they relate to dopamine signaling and the physiology of appetite control.
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10.1016/j.tins.2007.06.004
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pubmed_920_16947
|
Microgravity acts on cellular systems on several levels. Cells of the immune system especially react rapidly to changes in gravity. In this study, we performed a correlative metabolomics analysis on short-term and long-term microgravity effects on primary human macrophages. We could detect an increased amino acid concentration after five minutes of altered gravity, that was inverted after 11 days of microgravity. The amino acids that reacted the most to changes in gravity were tightly clustered. The observed effects indicated protein degradation processes in microgravity. Further, glucogenic and ketogenic amino acids were further degraded to Glucose and Ketoleucine. The latter is robustly accumulated in short-term and long-term microgravity but not in hypergravity. We detected highly dynamic and also robust adaptative metabolic changes in altered gravity. Metabolomic studies could contribute significantly to the understanding of gravity-induced integrative effects in human cells.
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10.3390/ijms22136752
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pubmed_291_9292
|
BACKGROUND
Epidemiological studies suggest that cigarette smoking - probably by eliciting hyperperfusion - increases glomerular filtration rate; thus, we hypothesized that cigarette smoke affects the vasomotor tone of renal arteries.
MATERIALS AND METHODS
Acute changes in the resistance index of a segmental renal artery were measured in healthy individuals during smoking. In addition, the effects of water-soluble components of cigarette smoke on the isometric tension of isolated rat renal arteries were investigated in various conditions.
RESULTS
In humans, cigarette smoking transiently reduced the resistance index of the renal artery segments (83·25 ± 5·67% of the baseline, P < 0·05). In the experimental model, water-soluble components of cigarette smoke (wCS) - either nicotinic or nicotine-free - elicited dose-dependent relaxations of rat isolated renal arteries (1% solution of nicotinic wCS: 41·18 ± 14·86% relaxation, 5% nicotinic wCS: 79·28 ± 8·91% relaxation, 10% nicotinic wCS 90·3 ± 6·1% relaxation, P < 0·05), which were not affected by removal of the endothelium, or by the soluble guanylate cyclase inhibitor oxadiazolo-quinoxalin-1, or the non specific potassium channel blocker tetraethylammonium, or the K(ATP) channel blocker glibenclamide. However, relaxations were reduced by catalase (1000 U mL⁻¹ catalase + 5% nicotinic wCS: 49·71 ± 18·4%, P < 0·05) and enhanced by superoxide dismutase (200 U mL⁻¹ SOD + 5% nicotinic wCS: 95·7 ± 2·3%, P < 0·05).
CONCLUSIONS
On the basis of these findings, we propose that cigarette smoking could contribute to the increased glomerular filtration rate observed in healthy smokers. In addition, cigarette smoke via hydrogen peroxide mediation reduces vasomotor tone of renal arteries, which could lead to hyperperfusion of kidneys.
|
10.1111/j.1365-2362.2010.02386.x
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pubmed_463_14707
|
Helicobacter pylori infects nearly 50% of the world's population. This microorganism is accepted as the most important agent of gastritis and as a risk factor for peptic ulcer disease and gastric adenocarcinoma. Currently many diagnostic methods exist for detecting H. pylori, however they all have limitations, thus it is recommend a combination of at least two methods. The aim of this study was to evaluate diagnostic methods, such as in-house urease test, culture and Polymerase Chain Reaction (PCR), for the detection of the H. pylori in gastric biopsy specimens of 144 dyspeptic patients, using as gold standard the association between histology and rapid urease test. According to the gold standard used in this study, 48 (33.3%) patients were infected with H. pylori, while 96 (66.7%) were classified as not infected. The in-house urease test and the PCR were the most sensitive methods (100%), followed by culture (85.4%). However, the inhouse urease test and the culture were the most specific (100%), followed by PCR (75%). In conclusion, this study showed that, in comparison with the combination of histology and rapid urease test, the in-house urease test and the PCR presented 100% of sensitivity in the diagnosis of gastric infection by H. pylori, while the in-house urease test and the culture reached 100% of specificity. These finding suggest that the combination of two or more methods may improve the accuracy of the H. pylori detection.
|
10.1590/S1517-83822012000300008
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pubmed_394_1242
|
Diabetic nephropathy is a major microangiopathic complication of diabetes mellitus. Its features are represented by: proteinuria and renal function decrease. The etiology of proteinuria in diabetic patients is assessed in this study. The study was performed on 30 patients with diabetes mellitus (11 type 1, 19 type 2) and proteinuria (19 males and 11 females), at the mean age of 42.1+/-7.72 years. Renal biopsies were done with Vim-Silverman needle, using hematoxylin-eosin and PAS staining. Diabetic retinopathy was found in 26 patients (86.66%). The values of proteinuria were: 0.62+/-0.07 g/24 hours in 4 (13.33%), 2.41+/-1.26 g/24 hours in 10 (33.33%) and 4.68+/-2.11 g/24 hours in 16 patients (53.33%). 18 patients presented elevated blood pressure (170.11+/-6.25/97.12+/-4.44 mmHg). Reduced creatinine clearance (48.01+/-7.25 ml/min) was found in 7 patients (23.33%). Histological analysis showed: diffuse diabetic glomerular lesions in 14 patients (46.66%), nodular diabetic glomerular lesions associated with diffuse glomerular lesions in 12 patients (40%) and membranous glomerulonephritis, without diabetic lesions in 4 patients (13.33%). Appearance of proteinuria in diabetic patients is not synonymous with diabetic nephropathy, requiring further investigations. including renal biopsy.
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pubmed_394_1242
|
pubmed_813_2800
|
Culture of keratinocytes in conventional medium without a mesenchyme-derived feeder layer leads to poor growth and impaired differentiation; however, the exact pathway and degree of differentiation achieved in such conditions is unclear. We have cultured normal human keratinocytes in Rheinwald and Green's medium, on plastic without a feeder layer, in order to investigate the degree of differentiation that they achieve in these conditions. Intermediate filament proteins, tonofibrils and desmosomes were assumed as markers of differentiation and their expression was analyzed by immunohistochemistry and electron microscopy. Before reaching confluence, keratinocytes expressed keratin molecules, as well as vimentin, and formed tonofibrils and desmosomes. The expression of these markers was progressively reduced until confluence and was totally lost thereafter, while cultures could be propagated for at least six passages. On the contrary, reseeding on a feeder layer after the first passage led to rapid cell death. It could be concluded that signals from a feeder layer are relevant to support continuous synthesis of intermediate filaments proteins and formation of tonofibils and desmosomes, and that the derangement of the cytoskeleton in these conditions leads to altered, not simply defective, response to delayed stimulation by a feeder layer.
|
10.14670/HH-14.797
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pubmed_950_11054
|
BACKGROUND
We investigated changes in the interferon-γ levels before and after treatment of latent tuberculosis infection (LTBI) using QuantiFERON-TB Gold Plus (QFT-Plus) and QuantiFERON-TB Gold In-Tube (QFT-GIT) assays. The objective was to assess whether QFT-Plus could serve as a biomarker of LTBI treatment response.
METHODS
We prospectively enrolled 44 individuals whose baseline QFT-GIT and QFT-Plus showed positive results at a tertiary referral center in South Korea between March 2017 and March 2018. The results of the QFT-Plus assay were defined as positive if either or both of the antigen tubes (TB1 and/or TB2) were positive. After LTBI treatment, both tests were repeated.
RESULTS
The mean age of the participants was 47.6 years. The QFT-GIT and QFT-Plus assays revealed positive results in 42/44 (95.5%) and 41/44 (93.2%) participants after LTBI treatment, showing overall agreement of 93.2%, with a Cohen's kappa value of 0.37 (fair agreement). The differences between pre- and post-LTBI treatment interferon-γ levels were measured using the QFT-GIT and QFT-Plus assays. No significant differences were noted among the 3 values: the median difference in interferon-γ value with QFT-GIT, QFT-Plus TB1, and QFT-Plus TB2 was 0.211 IU/mL (IQR, -0.337-3.347), 0.025 IU/mL (IQR, -0.338-1.368), and 0.180 IU/mL (IQR, -0.490-2.278), respectively (P = 0.401).
CONCLUSION
The change in interferon-γ levels before and after LTBI treatment measured using the QFT-Plus assay showed a similar trend to that of the QFT-GIT assay. Considering that the QFT-GIT assay is not a useful biomarker of LTBI treatment response, QFT-Plus also appears not to be useful for this purpose.
|
10.1371/journal.pone.0234700
|
pubmed_190_940
|
BACKGROUND AND PURPOSE
We aim to report the "deep tiny flow voids" (DTFV), a unique HR-MRI finding suggestive of deep collateral vessels along middle cerebral artery (MCA) occlusions.
METHODS
We retrospectively reviewed the HR-MRI data of 60 patients with unilateral MCA occlusion (32 symptomatic and 28 asymptomatic) and 205 control subjects with normal MCA on magnetic resonance angiography. The presence or absence of DTFV, defined as three or more flow voids along the occluded MCA on at least two consecutive T2-weighted image slices, was observed. The relationships among DTFV, clinical presentations, and infarct sizes were analyzed.
RESULTS
DTFV were identified in 20/28 (71%) patients with asymptomatic MCA occlusions, much more frequently than in the patients with symptomatic occlusions (5/32, 16%) (P<0.001). There were 9 patients with a large territorial infarction (≥ 1/3 MCA distribution), none of whom had DTFV on HR-MRI. DTFV was not observed in any control subject.
CONCLUSIONS
DTFV are pathological conditions and associated with relatively good imaging outcomes and asymptomatic MCA occlusions. The function and clinical implications of DTFV warrant further investigations.
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pubmed_190_940
|
pubmed_763_20413
|
Pre-eclampsia (PE) is a complication of pregnancy that affects 5‑8% of women after 20 weeks of gestation. It is usually diagnosed based on the de novo onset of hypertension and proteinuria. Preexisting hypertension in women developing PE, also known as superimposed PE on chronic hypertension (SPE), leads to elevated risk of maternal and fetal mortality. PE is associated with an altered microRNA (miRNA) expression pattern in the placenta, suggesting that miRNA deregulation is involved in the pathogenesis of PE. Whether and how the miRNA expression pattern is changed in the SPE placenta remains unclear. The present study analyzed the placental miRNA expression profile in pregnancies complicated by SPE. miRNA expression profiles in SPE and normal placentas were investigated using an Ion Torrent sequencing system. Sequencing data were processed using a comprehensive analysis pipeline for deep miRNA sequencing (CAP‑miRSeq). A total of 22 miRNAs were identified to be deregulated in placentas from patients with SPE. They included 16 miRNAs previously known to be associated with PE and 6 novel miRNAs. Among the 6 novel miRNAs, 4 were upregulated (miR‑518a, miR‑527, miR‑518e and miR‑4532) and 2 downregulated (miR‑98 and miR‑135b) in SPE placentas compared with controls. The present results suggest that SPE is associated with specific alterations in the placental miRNA expression pattern, which differ from alterations detected in PE placentas, and therefore, provide novel targets for further investigation of the molecular mechanisms underlying SPE pathogenesis.
|
10.3892/mmr.2016.5268
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pubmed_855_13077
|
Trabecularmeshwork (TM), a smooth muscle-like tissue with contractile properties, is involved in the regulation of aqueous humor outflow. However, little is known about the regulation of Ca(2+)influx in trabecular meshwork cells. We investigated the influence of acetylcholine and tyrosine kinases on Ca(2+)conductances of bovine TM (BTM) and human TM (HTM) cells using the perforated-patch configuration of the patch-clamp technique and measurements of intracellular free Ca(2+)([Ca(2+)](i)). Depolarization of the cells in the presence of 10 m m Ba(2+)or Ca(2+)led to an activation of inward currents at potentials positive to -30 mV with characteristics typical of L-type Ca(2+)currents: when using 10 m m Ba(2+), maximal inward current and inactivation time constant (tau) increased; the L-type Ca(2+)channel blocker nifedipine (1 microm) reduced and the L-type Ca(2+)channel agonist BayK8644 (5 microm) enhanced maximal inward current. Acetylcholine (100 microm) and carbachol (1 microm) led to an increase in inward Ba(2+)current whereas application of the tyrosine kinase inhibitors genistein (50 microm) and lavendustin A (20 microm) resulted in a decrease in inward current. The application of daidzein (10 microm), an inactive analog of genistein had no effect. Depolarization of the cells with 135 m m K(+)or direct stimulation of L-type channels by application of BayK 8644 led to an increase in [Ca(2+)](i). Carbachol (1 microm) induced an increase in [Ca(2+)](i)which was decreased by application of the tyrosine kinase inhibitor genistein (50 microm). We conclude that HTM and BTM cells express voltage-dependent L-type Ca(2+)channels that influence intracellular Ca(2+)concentration and thus may modulate TM contractility. The activity of L-type Ca(2+)currents is influenced by muscarinic agonists and tyrosine kinases.
|
10.1006/exer.1999.0785
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pubmed_298_24110
|
OBJECTIVE
To study the expression level of folate receptor α (FR-α) in glioma tissue and its clinical significance.
METHODS
Forty-eight human glioma specimens were collected from patients who underwent surgery from March 2012 to March 2013. These specimens were as follows:12 cases of glioblastoma (WHO IV), 6 cases of astrocytoma of each malignancy grade(WHO II, III), 6 cases of oligodendroastrocytoma of each malignancy grade (WHO II, III), 6 cases of oligodendroglioma of each malignancy grade (WHO II, III ). In addition, 6 cases of normal brain tissue resected from brain traumatic patients were taken as negative control, and one case of placental tissue (had got the consent of the parents and their families) was taken as positive control. The expression level of FR-α in tumor tissues was evaluated by Western blot analysis. The results of Western blot analysis were analyzed by t-test. The expression level of FR-α and Ki-67 in tumor tissues was evaluated immunohistochemistry, the results were analyzed by Kruskal-Wallis test and Nemenyi test. The correlation between the expression level of FR-α and cell proliferation index Ki-67 was analyzed by Pearson correlation analysis.
RESULTS
Western blot analysis showed that the FR-α was not expressed in normal brain tissue and oligodendroglioma tissue, but highly expressed in astrocytoma, oligodendroastrocytoma and gliomablastoma. The expression level in WHO III astrocytoma was significantly higher than in WHO II (t = 4.497, P < 0.05). FR-α was also highly expressed in oligodendroastrocytoma and its expression level in WHO III was also significantly higher than in the WHO II (t = 2.876, P < 0.05). Foremore, immunohistochemistry analysis also showed that FR-α was not expressed in oligodendroglioma, but expressed in astrocytoma, oligodendroastrocytoma and gliomablastoma. The positive rate of FR-α of WHO III was significantly higher than the WHO II astrocytoma(57.8% ± 2.2% vs. 45.7% ± 2.3%,χ(2) = 3.871, P = 0.034). In oligodendroastrocytoma, the positive rate of FR-α of WHO III was significantly higher than the WHO II(56.5% ± 5.4% vs. 37.1% ± 5.2%,χ(2) = 4.454, P = 0.021). Moreover, the expression level of FR-α in gliomablastoma was highest in all histological types of gliomas, the positive rate of FR-α was up to 65.0% ± 4.5%. Pearson correlation analysis showed that the positive rate of FR-α was positively correlated with Ki-67 index (r = 0.903, P < 0.05).
CONCLUSIONS
FR-α is expressed in astrocytoma, oligodendroastrocytoma and glioblastoma, and the expression level of FR-α is positively correlated with malignancy grade and Ki-67 index. Therefore, FR-α may be applied as a special target for diagnosis and treatment of glioma.
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pubmed_298_24110
|
pubmed_916_2136
|
OBJECTIVES
CTLA-4 exon-1 +49A > G (rs231775) polymorphism has been reported to influence the risk for primary biliary cirrhosis (PBC) as well as type I autoimmune hepatitis (AIH-1) in many studies; however, the results still remain controversial and ambiguous. This study aimed to determine more precise estimations for the relationship between CTLA-4 +49 A > G polymorphism and the risk for PBC and AIH-1 by using a meta-analysis.
DESIGN AND METHODS
PubMed, EMBASE and MEDLINE were searched. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to estimate the strength of the association.
RESULTS
Fifteen studies including 3661 patients with PBC and 4427 controls as well as seven studies including 1270 patients with AIH-1 and 1614 controls were identified. Our pooled analysis revealed that G allele of CTLA-4 gene +49A/G polymorphism may confer an increased risk of PBC in overall (p = 0.001, OR = 1.29; 95% CI = 1.13-1.47) and Caucasians (p = 0.001, OR = 1.32; 95% CI = 1.21-1.44). At genotypic level, the codominant, dominant and recessive models showed no significant association with PBC. With respect to AIH-1, the AG genotype demonstrated a trend for association with increased risk of AIH-1 (p = 0.04, AG vs. AA, OR = 1.20; 95% CI = 1.01-1.43). However, the CTLA-4 alleles as well as genotypes in dominant and recessive models were not associated with a risk for AIH-1 in both Caucasians and Asians.
CONCLUSIONS
This meta-analysis concluded that the CTLA-4 G allele and the AG genotype were associated with an increased risk for PBC and AIH-1, respectively, suggesting the CTLA-4 +49 A/G polymorphism as a candidate of susceptibility locus to PBC and AIH-1.
|
10.3109/08820139.2014.1003651
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pubmed_505_3455
|
A cell synchronization protocol was established in which global and individual mRNA translational efficiencies could be examined. While global translational efficiency was reduced in mitotic cells, approximately 3% of mRNAs remained predominantly associated with large polysomes during mitosis, as determined by cDNA microarray analyses. The 5'-non-coding regions of six mRNAs were shown to contain internal ribosome entry sites (IRES). However, not all known mRNAs that contain IRES elements were actively translated during mitosis, arguing that specific IRES sequences are differentially regulated during mitosis.
|
10.1074/jbc.M312854200
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pubmed_944_4484
|
INTRODUCTION
Subclinical neuropathy is an important feature of spinocerebellar ataxias (SCA) but the true prevalence and electrophysiological characteristics in genetically proven patients of SCA 1, 2 and 3 are largely unknown.
METHODS
We prospectively compared the electrophysiological characteristics of neuropathy in 61 genetically confirmed cases of SCA (SCA1=28, SCA2=16 and SCA3=17). Nerve conduction studies were performed in at least one sensory and one motor nerve, in right upper and lower limb using standard methods.
RESULTS
The mean age of patients and duration of illness were comparable among SCA groups (mean age (years): SCA1-34.1±12.7, SCA2-35.2±13.9 and SCA3-38.1±11.3; mean duration (years): SCA1-5.4, SCA2-6.1, and SCA3-4.4). Electrophysiological evidence of neuropathy was highest in SCA1 (96.4%), followed by SCA3 (94.1% and SCA2 (87.5%). A mixed sensorimotor neuropathy was commonly observed in all the subgroups (SCA1-78.6%, SCA2-50%, and SCA3-41.2%). Pure sensory neuropathy was most common in SCA3 (55.9%), followed by 31.3% in SCA2 and 17.9% in SCA1. Pure motor neuropathy was uncommon (6.3% in SCA2 and none in SCA1 and SCA3).
CONCLUSIONS
Electrophysiological evidence of mixed sensorimotor and pure sensory neuropathy is seen in all the three subtypes of SCAs, while pure motor neuropathy is distinctly uncommon.
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10.1016/j.jns.2011.07.051
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pubmed_343_8724
|
The objective of this study was to investigate the effects of diets supplemented with sodium stearoyl-2-lactylate (SSL), polyglycerol fatty acid ester (PGFE), and combined emulsifiers (0.02% SSL and 0.08% PGFE) on growth performance, nutrient digestibility, and plasma lipid profiles in weaned piglets and to further evaluate the possible effects of feeding exogenous emulsifiers on digestive enzyme activities and liver bile acid (BA) metabolism. Twenty-eight barrows (age at 35 d, Duroc × Landrace × Yorkshire) with an initial BW of 10.13 ± 0.16 kg were randomly assigned to 4 dietary treatment groups (7 pigs/treatment). Dietary treatment groups included the following: 1) basal diet (Control, CTR); 2) basal diet with 0.1% SSL (SSL); 3) basal diet with 0.1% PGFE (PGFE); and 4) basal diet with 0.08% PGFE+0.02% SSL (PG-SL). SSL diet increased ADG and ADFI of piglets during day 0 to 17 (P < 0.05) compared with the CTR treatment. Piglets fed emulsifier diets experienced a significant improvement in the digestibility of nutrients (DM, CP, ether extract, energy, calcium, and phosphorus) during the first 17 d (P < 0.05). The level of low-density lipoprotein cholesterol (LDL-C) was lower in the PGFE and PG-SL treatment groups than in the CTR treatment group (P < 0.05). Feeding emulsifier diets increased the lipase activity of the pancreas when compared with the CTR diet (P < 0.05). Moreover, the emulsifier diets significantly increased the mRNA expression of FXR (P < 0.05) and decreased the mRNA expression of CYP27A1 (P < 0.05) in the liver. In conclusion, the addition of emulsifiers improved nutrient digestibility and increased the mRNA expression of FXR BA receptors while inhibiting the mRNA expression of BA biosynthesis by CYP27A1 in weanling piglets.
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10.1093/jas/skz276
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pubmed_248_5344
|
Campylobacter is the most common bacterial cause of gastroenteritis in England and Wales, with 45000 cases reported annually. Campylobacter incidence is highly seasonal; the consistent peak in late spring suggests a role for meteorological factors in the epidemiology of this organism. We investigated the relationship between ambient temperature and Campylobacter enteritis using time-series analysis to study short-term associations between temperature and number of Campylobacter reports adjusted for longer-term trend and seasonal patterns. We found a linear relationship between mean weekly temperature and reported Campylobacter enteritis, with a 1 degrees C rise corresponding to a 5% increase in the number of reports up to a threshold of 14 degrees C. There was no relationship outside this temperature range. Our findings provide evidence that ambient temperature influences Campylobacter incidence, and suggest that its effect is likely to be indirect, acting through other intermediate pathways.
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10.1017/S0950268805004899
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pubmed_315_12805
|
Forward and retrograde trafficking of secretory proteins between the endoplasmic reticulum and the Golgi apparatus is driven by two biochemically distinct vesicle coats, COPI and COPII. Assembly of the coats on their target membranes is thought to provide the driving force for membrane deformation and the selective packaging of cargo and targeting molecules into nascent transport vesicles. This review describes our current knowledge on these issues and discusses how the two coats may be differentially targeted and assembled to achieve protein sorting and transport within the early secretory pathway.
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10.1016/0962-8924(96)84943-9
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pubmed_206_13764
|
Recent studies have reported that chemically synthesized small duplex RNAs complementary to promoters of target genes can specifically induce gene expression in several cancer cell lines. Such dsRNA, referred to as small activating RNA (saRNA), are involved in the recently described phenomenon called RNA activation (RNAa). Recent findings show that saRNA can inhibit cell proliferation and viability via up-regulation of p21(WAF1/CIP1) (p21) in human bladder cancer cells. In the present study, we demonstrate that induction of E-cadherin expression by saRNA leads to suppression of migration and invasion of 5637 human bladder cancer cells in vitro. The elevated E-cadherin expression was confirmed at transcriptional and protein levels after transfection of a 21-nucleotide dsRNA targeting the E-cadherin promoter (dsEcad). Furthermore, this inhibitory effect was associated with relocalization of beta-catenin from the nucleus to the plasma membrane and decreased beta-catenin-mediated transactivation. These data suggest that activation of E-cadherin by saRNA may have a therapeutic benefit for bladder and other types of cancer.
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10.1016/j.bbrc.2008.08.059
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pubmed_1124_1513
|
Recently, the U.S. Surgeon General described two aspects of national health that require our immediate attention: As a nation, we are becoming increasingly more sedentary and more overweight. Furthermore, he and some of the most prominent health agencies have suggested that one of the primary strategies to overcome what is viewed as a national epidemic is the promotion of quality physical education in our schools. This paper describes in brief the facts associated with this concern, what is meant by quality physical education, and the role of the school nurse in helping to promote physical education in the schools.
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10.1177/105984050101700203
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pubmed_892_20306
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The nurse executive at the corporate level is in a pivotal position to provide balance between the provision of integrated patient care and success of the corporate mission. In this role, the nurse executive shifts the spotlight from a solely nursing perspective to the systems approach in support of patient care. The response that follows is often a redoubling of the efforts of health care providers to render more efficient and cohesive care to patients. In the end, success is an outgrowth of strong teamwork combined with the ability of the executive to connect the corporate business strategy with the provision of patient care wherever it is delivered.
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10.1097/00006216-199602020-00011
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pubmed_36_15635
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Histochemistry provides the unique opportunity to detect single molecules in the very place where they exert their structural roles or functional activities: this makes it possible to correlate structural organization and function, and may be fruitfully exploited in countless biomedical research topics. Aiming to estimate the impact of histochemical articles in the biomedical field, the last few years citations of articles published in a long-established histochemical journal have been considered. This brief survey suggests that histochemical journals, especially the ones open to a large spectrum of research subjects, do represent an irreplaceable source of information not only for cell biologists, microscopists or anatomists, but also for biochemists, molecular biologists and biotechnologists.
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10.4081/ejh.2014.2474
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pubmed_260_2887
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A putative UDP-N-acetyl-D-mannosamine dehydrogenase from Pyrococcus horikoshii OT3, an essential enzyme for polysaccharide biosynthesis, has been overexpressed in Escherichia coli and purified. Crystals were obtained using the oil-microbatch method at 291 K. A native data set extending to 1.8 A resolution has been collected and processed in space group P2(1). Assuming the presence of a dimer in the asymmetric unit, the V(M) value is calculated to be 2.3 A3 Da(-1), which is consistent with the result of a dynamic light-scattering experiment that shows a dimeric state of the protein in solution.
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10.1107/S1744309107016685
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pubmed_46_15283
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Toxoplasma gondii is a major cause of focal encephalitis in patients with acquired immunodeficiency syndrome. Epiroprim, an inhibitor of dihydrofolate reductase, was evaluated in vitro and in a mouse model of acute infection for activity against T. gondii. The 50% inhibitory concentration (IC50) of epiroprim for T. gondii dihydrofolate reductase was 0.9 micromole, similar to that of pyrimethamine, but epiroprim was 650-fold more selective than pyrimethamine for T. gondii compared with human dihydrofolate reductase. While intraperitoneally administered epiroprim (300 mg/kg/day for 14 days) alone was ineffective in mice acutely infected with the RH strain of T. gondii, 100% survival was seen when it was combined with orally administered sulfadiazine (375 mg/kg/day), which alone was also ineffective. Increases in survival were seen in combination with doses of sulfadiazine as low as 0.375 mg/kg/day. Orally administered epiroprim combined with dapsone also prolonged survival. Thus epiroprim is an active and potentially less toxic alternative pyrimethamine for the treatment of toxoplasmosis.
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10.4269/ajtmh.1996.54.249
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pubmed_158_3391
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The aim of the study was to evaluate the program of education of women for breast self-examination (BSE) in general practice. A random sample of 5% of women over 18 years of age, living in Dugave (a suburb in Novi Zagreb) were chosen for the study. The study covered 251 women of whom 122 (48.6%) presented for BSE training. Women were taught about BSE by the method which included the theoretical part, group discussion, practical training on silicon breast model, individual practice of BSE, and additional individual assessment of the acquired skill of BSE. Six months after the BSE training, out of 116 women presented for retesting, BSE was performed by 91 (78.4%) women: 75 (82.4%) performed BSE regularly once a month or in two months, while 60 (65.9%) women dedicated sufficient time to BSE. Assessment of BSE performance in our subjects showed palpation with the longer parts of fingers and palpation of the whole breast to be skills best mastered by the women. Palpation of the nipple area and palpation of the armpit were sections of BSE in which the women also achieved good results. It is surprising that breast inspection, easy as the procedure may seem, is the section of BSE in which the women did not achieve expected results. On the post-course assessment, as many as 15 (12.9%) women left out breast inspection, while 10 (8.6%) women performed breast inspection in a completely wrong way. Keeping self-records on BSE was by far the most poorly assessed part. Incomplete keeping of self-records on BSE findings is an important objection to BSE as a procedure which should contribute to the systematic continuous drive for early detection of breast cancer. The most important conditions for the education of women for BSE are the knowledge, ability and willingness of the GP and members of his team to provide health education to the population under their care. BSE is not the ultimate solution, but is a significant step in the continuous struggle against breast cancer. That is why it is essential that all women be informed about BSE and as many women as possible be covered by systematic education for BSE. Authors' results indicate that it is possible to implement the proposed model of continuous education of women for BSE within the scope of work of the GP's team.
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pubmed_158_3391
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pubmed_151_9493
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Liquid biopsies are increasingly used in the care of patients with advanced cancers. These tests are used to find mutations and other genomic alterations, quantify these findings over time, and guide treatment. It is not unexpected that germline mutations contributing to the development of cancer can be identified in cell-free DNA. Consequently, increased use of liquid biopsies has resulted in subsequent rise of secondary identification of germline mutations. Clinicians need to be aware of this potential use of liquid biopsies and the need to evaluate the patient and family members for confirmation. Our case documents a deceased patient's liquid biopsy result that was confirmed as a germline mutation through a methodical work-up of the patient's family members. Here, we present the case and provide a brief review of pertinent literature.
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10.3389/fonc.2018.00259
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pubmed_120_18275
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An elevated hydrostatic pressure in the endolymphatic space of the inner ear is discussed as pathophysiological factor in hydrops-related diseases of the inner ear. An increase in pressure by fractions of 1 cm H(2)O is sufficient to induce vertigo-like symptoms in animal models. To establish a link between hydrostatic pressure and the function of vestibular hair cells, we studied potassium currents in isolated vestibular type II hair cells from guinea-pig utricles when the hydrostatic pressure was increased by raising the height of the bath from 0.2-0.5, 0.7 or 1.0 cm. Elevated pressure enhanced K(+) currents significantly; a rise in pressure from 0.2-0.5 cm H(2)O increased the total K(+) current at +40 mV by 22+/-14% (+/-S.D.). The pressure-sensitive current I(K,p) was non-inactivating during depolarizing pulses. It was maintained when the pressure was kept elevated for several minutes and receded promptly after return to a pressure of 0.2 cm H(2)O. Voltage-gated Ca(2+) currents, in contrast, were not altered by hydrostatic pressure. A pharmacological characterization of I(K,p) revealed that tetraetylammonium (100 mM) abolished all outward currents including I(K,p). I(K,p) was partly and reversibly inhibited by 4-aminopyridine. Dihydrostreptomycin, a blocker of the transduction channel, left I(K,p) unaffected. Charybdotoxin (100 nM), a blocker of Ca(2+)-dependent K(+) channels, completely yet reversibly abolished I(K,p). We conclude that small elevations in hydrostatic pressure evoke a charybdotoxin-sensitive, probably Ca(2+)-dependent K(+) current in vestibular hair cells. This is likely to alter their frequency response and may be a relevant mechanism how hydrostatic pressure disturbs transduction.
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10.1016/s0306-4522(02)00776-5
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pubmed_954_2004
|
SIGNIFICANCE
Psoriasis, a common immune-mediated disease, affects approximately 2% of the population worldwide. Sudden sensorineural hearing loss (SSNHL) might be a manifestation of systemic vascular involvement in autoimmune disease. However, to the best of our knowledge, there is no systematic English-language examination of the risk of SSNHL in patients with psoriasis.
OBJECTIVES
We tested the hypothesis that psoriasis is a risk factor for developing SSNHL.
METHODS
Using Taiwan's National Health Insurance Research Database, we conducted a retrospective cohort study to compare patients diagnosed with psoriasis from January 1, 2001 through December 31, 2006 (n=28,817) with gender-, age-, and comorbidities-matched controls (n=28,817). We followed each patient until the end of 2011 and evaluated the incidence of SSNHL for at least 6 years after the initial psoriasis diagnosis.
RESULTS
The incidence of SSNHL was 1.51 times higher in the psoriasis cohort than in the control cohort (7.12 vs 4.73 per 10,000 person-years). Using Cox proportional hazard regressions, the adjusted hazard ratio (AHR) was 1.51 (95% confidence interval [CI] 1.18-1.93). Comorbid hypertension was an independent risk factor for SSNHL (AHR 1.49; 95% CI 1.05-2.13). However, the incidence rate ratios (IRRs) for each comorbidity subgroup in the psoriasis and control cohorts were not significantly different.
CONCLUSIONS AND RELEVANCE
Psoriasis was significantly associated with a higher risk of developing SSNHL. We suggest that physicians advise patients with psoriasis to seek medical attention if they have hearing impairments, because they may also have a higher risk of developing SSNHL.
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10.1007/s40257-015-0117-9
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pubmed_1066_11523
|
Africa is currently experiencing both financial and human development challenges. While several continents have advocated for financial development in order to acquire environmentally friendly machinery that produces less emissions and ensures long-term sustainability, Africa is still lagging behind the rest of the world. Similarly, Africa's human development has remained stagnant, posing a serious threat to climate change if not addressed. Building on the underpinnings of the environmental Kuznets curve (EKC) hypothesis on the nexus between economic growth and environmental pollution, this study contributes to empirical research seeking to promote environmental sustainability as follows. First, it investigates the link between financial development, human capital development and climate change in East and Southern Africa. Second, six advanced panel techniques are used, and they include (1) cross-sectional dependency (CD) tests; (2) combined panel unit root tests; (3) combined panel cointegration tests; (4) panel VAR/VEC Granger causality tests; and (5) combined variance decomposition analysis based on Cholesky and generalised weights. Our finding shows that financial and human capital developments are important in reducing CO2 emissions and promoting environmental sustainability in East and Southern Africa.
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10.1007/s11356-021-15129-1
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pubmed_222_215
|
Recent studies have reported ECG anomalies and a high prevalence of exercise-related arrhythmias among well trained, apparently healthy endurance athletes with superior levels of cardiorespiratory fitness. The occurrence of sudden and premature cardiac deaths in amateur and professional athletes, who appear to embody all of the virtues of health and fitness, ahs raised our consciousness regarding the underlying atherosclerotic or nonatherosclerotic causes, and the need for, and extent of, preparticipation screening in competitive athletes. It appears that strenuous physical activity may trigger acute cardiovascular events in some athletes. Coronary artery disease is the most frequent autopsy finding in those over the age of 35 years who die suddenly. In contrast, structural cardiovascular abnormalities, including hypertrophic cardiomyopathy and malformations of the coronary arteries, are the major cause of sudden death in younger athletes. This article reviews these issues, with specific reference to the assessment of cardiorespiratory fitness, legal and prohibited performance-altering medications, the pathophysiological basis of exertion-related untoward events, the athlete at risk, limitations of conventional screening programmes and contemporary recommendations to identify latent cardiovascular disease in athletic populations.
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10.2165/00007256-199724020-00003
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pubmed_1031_8412
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Patient-rated life satisfaction and observer-rated quality of life (ORQOL) appear to have different determinants in patients with schizophrenia, although most studies conducted to date have used cross-sectional methods or related clinical dimensions at one time point with quality of life (QOL) measured at another. The aim of this study was to investigate the relationship between changes in patient-rated QOL (PRQOL) and ORQOL over time and changes in clinical variables. Two hundred and thirty-one patients taking part in the Schizophrenia Care Assessment Program (SCAP) study at Dandenong in Australia were included in this analysis. Subjective ratings of several domains of social functioning and life satisfaction were taken from the SCAP instrument and comparisons made with data from the QOL Scale rated by research staff, as well as several psychopathology measures. Changes in these scores over 1 year were correlated to investigate relationships between measures. Weak correlations were seen between changes in PRQOL and ORQOL domains. Patient-rated domains related most closely to depressive symptoms (Montgomery-Asberg Depression Rating Scale scores) whereas observer-rated domains related to both negative symptoms and depressive symptoms. Positive psychotic symptoms had little effect on either domain. Longitudinal data appear to confirm that PRQOL and ORQOL are not closely related and may have differing determinants in patients with schizophrenia. They should be considered as separate and complementary outcome variables and utilized accordingly.
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10.1016/s0165-1781(03)00099-4
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pubmed_1030_9481
|
In late 2021, the omicron variant of SARS Coronavirus 2 (SARS-CoV-2) emerged and replaced the previously dominant delta strain. Effectiveness of COVID-19 vaccines against omicron has been challenging to estimate in clinical studies or is not available for all vaccines or populations of interest. T cell function can be predictive of vaccine longevity and effectiveness against disease, likely in a more robust way than antibody neutralization. In this mini review, we summarize the evidence on T cell immunity against omicron including effects of boosters, homologous versus heterologous regimens, hybrid immunity, memory responses and vaccine product. Overall, T cell reactivity in post-vaccine specimens is largely preserved against omicron, indicating that vaccines utilizing the parental antigen continue to be protective against disease caused by the omicron variant.
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10.3389/fimmu.2022.944713
|
pubmed_764_20109
|
BACKGROUND
Disordered breathing among patients with panic disorder, including hyperventilation during attacks and increased anxiogenic response to carbon dioxide (CO2) inhalation, is well established. We wished to assess whether there is a change in the physiological response to CO2 after patients have undergone antipanic therapy with either tricyclic antidepressants or cognitive behavioral therapy (CBT).
METHODS
Twenty-nine patients with panic disorder underwent baseline CO2 sensitivity testing using the traditional Read rebreathing method and then received either antidepressant treatment (n = 21) or CBT (n = 8). After completing treatment, CO2 testing was repeated. A comparison sample of 14 normal volunteers also had two CO2 sensitivity tests, separated by an average of 21.6 (SD = 8.8) weeks.
RESULTS
Using a liberal standard, in which all CO2 sensitivity tests whose correlations between minute ventilation and end-tidal CO2 were at least .75 were used, patients, but not controls, demonstrated a significant reduction in CO2 sensitivity between the first and second test. Using a more conservative .90 correlation standard reduced the sample size available and resulted in trend reduction in patients but no significant change in controls. There was a suggestion that the change was most pronounced in treatment responders, although the number of patient nonresponders is extremely small in this sample.
CONCLUSIONS
These data indicate that treatment reduces CO2 sensitivity in patients with panic disorder. We speculate that manipulation of the serotonergic and noradrenergic neurotransmission systems, both known to play a role in the control of respiration, may have a specific effect in reducing respiratory hyperactivity in panic disorder.
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10.1016/s0006-3223(97)00160-1
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pubmed_1003_2477
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Normobaric intermittent hypoxic training (IHT) is an effective method for improvement of the FRS state, increase of the aerobic productivity, as well as general and special capacity for work in sportsmen of high qualification. High efficacy of IHT in improving all aspects of sportsmen FRS is a result of alternating the hypoxic influences and normoxic intervals between them during which the level of plastic processes remains increased, oxygen tension in arterial blood and tissues increases to nonnoxic values. After IHT course, the state of organ respiration improves, the respiration volume, a part of alveolar ventilation in the minute volume of respiration, oxygen saturation of arterial blood, hemoglobin content in blood--increase as well as economy and efficacy of oxygen regimes of organism, general and special (especially important) physical capacity for work.
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pubmed_1003_2477
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pubmed_105_1635
|
(1) Background: Previous research revealed that increased loneliness resulted in decreased meaning in life (MIL). Little is known, however, about the underlying mechanisms of this relationship. The aim of the study was to determine if the set of positive evaluations of oneself, one's life, and one's future discussed by Caprara as positive orientation (POS) was a mediator between loneliness and MIL. (2) Methods: A sample of 304 Polish participants aged 19-45 (M = 25.61 years, SD = 6.1) completed the De Jong Gierveld Loneliness Scale, the Presence subscale of the Meaning in Life Questionnaire, and the Positivity Scale. (3) Results: The study showed that loneliness was negatively associated with POS and MIL, while POS and MIL were positively correlated with each other. It also turned out that POS partially mediated the relationship between loneliness and MIL. (4) Conclusions: The results suggest that, by inhibiting POS, loneliness makes it difficult to perceive life as meaningful. The interrelationships between loneliness, POS, and MIL are discussed in light of the evolutionary theory of loneliness.
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10.3390/ijerph19169948
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pubmed_747_9926
|
A case of pneumatosis coli of the caecum and ascending colon with a closed loop obstruction secondary to carcinoma of the descending colon is presented. The caecum was grossly distended and impending rupture was diagnosed. It is postulated that complete transmural rupture of the caecum was prevented by partial decompression of caecal air into the bowel wall.
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pubmed_747_9926
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pubmed_463_15311
|
Amoitone B, a novel compound chemically synthesized as the analogue of cytosporone B, has been proved to own superior affinity with Nur77 than its parent compound and exhibit notable anticancer activity. However, its application is seriously restricted due to the water-insolubility and short biological half-time. The aim of this study was to construct an effective delivery system for Amoitone B to realize sustained release, thus prolong drug circulation time in body and improve the bioavailability. Nanostructured lipid carriers (NLC) act as a new type of colloidal drug delivery system, which offer the advantages of improved drug loading and sustained release. Amoitone B-loaded NLC (AmB-NLC) containing glyceryl monostearate (GMS) and various amounts of medium chain triglycerides (MCT) were successfully prepared by emulsion-evaporation and low temperature-solidification technology with a particle size of about 200 nm and a zeta potential value of about -20 mV. The results of X-ray diffraction and DSC analysis showed amorphous crystalline state of Amoitone B in NLC. Furthermore, the drug entrapment efficacy (EE) was improved compared with solid lipid nanoparticles (SLN). The EE range was from 71.1% to 84.7%, enhanced with the increase of liquid lipid. In vitro drug release studies revealed biphasic drug release patterns with burst release initially and prolonged release afterwards and the release was accelerated with augment of liquid lipid. These results demonstrated that AmB-NLC could be a promising delivery system to control drug release and improve loading capacity, thus prolong drug action time in body and enhance the bioavailability.
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10.3109/10717544.2013.835007
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pubmed_257_6944
|
The portal blood velocity and flow were measured by means of pulsed echo-Doppler in 60 normal subjects of 4 different age groups (less than or equal to 40, 41-55, 56-70, greater than or equal to 71 years). All subjects had normal routine liver function tests and no history of liver disease. Portal blood velocity decreased from 15.7 +/- 3.2 cm/s in younger subjects to 12.4 +/- 1.7 in subjects over 71 years (ANOVA: p = 0.005). Similarly portal blood flow decreased (p = 0.025). Both portal blood velocity and flow were inversely correlated with age (r = -0.583 and -0.505, respectively). No changes in portal vein diameter were observed. The age-related decline in portal flow may account for the decrease in hepatic blood flow previously documented in the elderly.
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10.1159/000213000
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pubmed_328_7029
|
BACKGROUND
Antibodies targeting the immune checkpoint molecules PD-1 or PD-L1 have demonstrated clinical efficacy in patients with metastatic non-small-cell lung cancer (NSCLC). In this trial we investigated the efficacy and safety of avelumab, an anti-PD-L1 antibody, in patients with NSCLC who had already received platinum-based therapy.
METHODS
JAVELIN Lung 200 was a multicentre, open-label, randomised, phase 3 trial at 173 hospitals and cancer treatment centres in 31 countries. Eligible patients were aged 18 years or older and had stage IIIB or IV or recurrent NSCLC and disease progression after treatment with a platinum-containing doublet, an Eastern Cooperative Oncology Group performance status score of 0 or 1, an estimated life expectancy of more than 12 weeks, and adequate haematological, renal, and hepatic function. Participants were randomly assigned (1:1), via an interactive voice-response system with a stratified permuted block method with variable block length, to receive either avelumab 10 mg/kg every 2 weeks or docetaxel 75 mg/m2 every 3 weeks. Randomisation was stratified by PD-L1 expression (≥1% vs <1% of tumour cells), which was measured with the 73-10 assay, and histology (squamous vs non-squamous). The primary endpoint was overall survival, analysed when roughly 337 events (deaths) had occurred in the PD-L1-positive population. Efficacy was analysed in all PD-L1-positive patients (ie, PD-L1 expression in ≥1% of tumour cells) randomly assigned to study treatment (the primary analysis population) and then in all randomly assigned patients through a hierarchical testing procedure. Safety was analysed in all patients who received at least one dose of study treatment. This trial is registered with ClinicalTrials.gov, number NCT02395172. Enrolment is complete, but the trial is ongoing.
FINDINGS
Between March 24, 2015, and Jan 23, 2017, 792 patients were enrolled and randomly assigned to receive avelumab (n=396) or docetaxel (n=396). 264 participants in the avelumab group and 265 in the docetaxel group had PD-L1-positive tumours. In patients with PD-L1-positive tumours, median overall survival did not differ significantly between the avelumab and docetaxel groups (11·4 months [95% CI 9·4-13·9] vs 10·3 months [8·5-13·0]; hazard ratio 0·90 [96% CI 0·72-1·12]; one-sided p=0·16). Treatment-related adverse events occurred in 251 (64%) of 393 avelumab-treated patients and 313 (86%) of 365 docetaxel-treated patients, including grade 3-5 events in 39 (10%) and 180 (49%) patients, respectively. The most common grade 3-5 treatment-related adverse events were infusion-related reaction (six patients [2%]) and increased lipase (four [1%]) in the avelumab group and neutropenia (51 [14%]), febrile neutropenia (37 [10%]), and decreased neutrophil counts (36 [10%]) in the docetaxel group. Serious treatment-related adverse events occurred in 34 (9%) patients in the avelumab group and 75 (21%) in the docetaxel group. Treatment-related deaths occurred in four (1%) participants in the avelumab group, two due to interstitial lung disease, one due to acute kidney injury, and one due to a combination of autoimmune myocarditis, acute cardiac failure, and respiratory failure. Treatment-related deaths occurred in 14 (4%) patients in the docetaxel group, three due to pneumonia, and one each due to febrile neutropenia, septic shock, febrile neutropenia with septic shock, acute respiratory failure, cardiovascular insufficiency, renal impairment, leucopenia with mucosal inflammation and pyrexia, infection, neutropenic infection, dehydration, and unknown causes.
INTERPRETATION
Compared with docetaxel, avelumab did not improve overall survival in patients with platinum-treated PD-L1-positive NSCLC, but had a favourable safety profile.
FUNDING
Merck and Pfizer.
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10.1016/S1470-2045(18)30673-9
|
pubmed_437_6350
|
A novel radical phosphinylation of α,α-diaryl allylic alcohols with arylphosphine oxides was described for the direct preparation of α-aryl-β-phosphinylated carbonyl ketones in medium to good yields via 1,2-aryl migration. In this reaction, formation of new C(Ar)-C(sp(3)) and C(sp(3))-P bonds was observed.
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10.1039/c4cc02114b
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pubmed_641_21454
|
The role of cellular membranes in thymocyte apoptosis has been examined. Trolox, a water soluble analogue of vitamin E and inhibitor of membrane damage, inhibits DNA fragmentation in thymocytes exposed to gamma-radiation. Trolox is most effective in inhibiting DNA fragmentation when added to cells within 30 min post-irradiation. Exposure to trolox only during irradiation did not prevent DNA fragmentation, suggesting that it does not work by scavenging free radicals generated during radiation exposure. Incubation of the irradiated cell suspension with trolox for 2 h post-irradiation was sufficient to prevent DNA fragmentation measured at 24 h in irradiated cells. This suggests that trolox irreversibly inhibits a cellular lesion required for apoptosis. The induction of DNA fragmentation appears to be related to a concurrent, pronounced flow of Ca2+ into the cell. At 3 h post-irradiation the amount of Ca2+ in irradiated thymocytes was more than twice that of unirradiated thymocytes. Membrane damage has been shown to affect the transport of Ca2+. Trolox treatment completely blocked the radiation-induced influx of Ca2+ into the thymocytes. These results suggest that membrane damage is a critical lesion that is involved in DNA fragmentation in thymocyte apoptosis.
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10.1080/09553009314552091
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pubmed_497_5213
|
BACKGROUND
Placebo-controlled randomized trials of platelet glycoprotein (GP) IIb/IIIa blockade during percutaneous coronary intervention have demonstrated efficacy of these agents for reducing the risk of periprocedural ischemic events. However, cost-effectiveness of this adjunctive pharmacotherapy has been scrutinized. Extrapolation of cost-efficacy observations from clinical trials to "real world" interventional practice is problematic.
METHODS
Consecutive percutaneous coronary interventions (n = 1472) performed by Ohio Heart Health Center operators at The Christ Hospital, Cincinnati, Ohio, in 1997 were analyzed for procedural and long-term (6-month) outcomes and charges. Observations on cost and efficacy (survival) were adjusted for nonrandomized abciximab allocation by means of "propensity scoring" methods.
RESULTS
Abciximab therapy was associated with a survival advantage to 6 months after percutaneous coronary intervention. The average reduction in mortality rate at 6 months was 3.4% (unadjusted) and 4.9% when adjusted for nonrandomization. The average charge increment to 6 months was $1512 (unadjusted) and $950 when adjusted for nonrandomization. Patients deriving the greatest reduction in mortality rates also had a reduction in total cardiovascular charges to 6 months. Distinguishing demographics of this population included multivessel coronary intervention, coronary stent deployment, intervention within 1 week of myocardial infarction, and lower left ventricular ejection fraction. The average cost per life-year gained in this study was $2875 for all patients (unadjusted) and $1243 when adjusted for nonrandomization.
CONCLUSIONS
Abciximab provides a cost-effective survival advantage in high-volume interventional practice that compares favorably with currently accepted standards. Clinical and procedural demographics associated with increased cost-effectiveness included multivessel coronary intervention, stent deployment, recent (<1 week) myocardial infarction, and impaired left ventricular function.
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10.1067/mhj.2000.109647
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pubmed_1034_23879
|
Resveratrol (RES) is the most effective natural products used for the treatment of a variety of cancers. In this study, we tested the effect of RES in enhancing the efficacy of docetaxel (DTX) treatment in prostate cancer (PCa) cells. The C4-2B and DU-145 cell lines were treated with RES, DTX and combination followed by evaluating the apoptosis and cell cycle progression. The combined drug treatment up-regulates the pro-apoptotic genes (BAX, BID, and BAK), cleaved PARP and down regulates the anti-apoptotic genes (MCL-1, BCL-2, BCL-XL) promoting apoptosis. In C4-2B cells the combination up regulated the expression of p53, and cell cycle inhibitors (p21WAF1/CIP1, p27KIP), which, in turn, inhibited the expression of CDK4, cyclin D1, cyclin E1 and induced hypo-phosphorylation of Rb thus blocking the transition of cells in the G0/G1 to S phase. In contrast, the synergistic effect was not profound in DU145 due to its lesser sensitivity to DTX. The suppression of cyclin B1 and CDK1 expression in both cell lines inhibits the further progression of cells in G2/M phase. The current study demonstrates that combination treatment blocks the cell cycle arrest by modulation of key regulators and promotes apoptosis via p53 dependent and independent mechanism in PCa.
|
10.18632/oncotarget.15303
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pubmed_567_7686
|
Flavoring systems are of vital importance in savory food manufacturing. Many industrially prepared foods are particularly attractive to potential consumers primarily because of their typical flavors. Therefore, it is no surprise that the food industry dealing with these product segments shows great interest in the use of food or food ingredients carrying the typical umami taste and flavor enhancement systems. Figures are provided showing the importance of glutamate in traditional cuisines and also in meals prepared by industrial manufacturing. It is also interesting to see how food intake patterns of glutamate differ from one cultural group to another. The ever-growing importance of balanced food formulations (carbohydrates, fats, proteins and minerals) brings special challenges to the use of different ingredients, requiring development of appropriate flavor delivery systems. Again flavor enhancement is of great importance. Questions about the addition of glutamate or the total glutamate content of foods are of little importance, from a scientific point of view. However, in a given legal framework, important business opportunities can be realized. One of the main concerns of manufacturers of savory food is how to provide the consumer with tasty foods while complying with increasingly severe local legal constraints concerning the use of many potent flavoring systems.
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10.1093/jn/130.4.915S
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pubmed_695_23225
|
PURPOSE
This study aims to assess the survival rate of oral squamous cell carcinoma (OSCC) patients following immediate mandibular reconstruction with vascularized fibula flap (VFF) and to identify risk factors influencing the overall survival rate and postoperative outcomes.
PATIENTS AND METHODS
Patients suitable for the inclusion criterion diagnosed and treated between January 1996 till June 2019 for OSCC were retrospectively reviewed (n = 74). Potential risk factors and postoperative outcomes were recorded and analyzed.
RESULTS
The overall cumulative survival rate of patients was 0.52 at the end of 5th year. Overall, advanced pN stage (p = 0.0422), poor tumor differentiation (p < 0.0001), positive/close surgical margins (p = 0.0209), vascular invasion (p = 0.0395), perineural invasion (p = 0.0022) and tumor recurrence (p = 0.0232) were significantly related to a decreased cumulative survival. Tumor recurrence was significantly correlated with involvement of positive/close surgical margins, moderate (p = 0.0488), poor-differentiated tumors (p = 0.202), extracapsular spread (p = 0.0465), computer-assisted surgery (p = 0.0014) and early complications (p = 0.0224). Pain was significantly associated with the extracapsular spread (p = 0.0353) and early complications (p = 0.0127).
CONCLUSION
The five-year survival rate of advanced OSCC patients after segmental mandibulectomy with fibula free-flap reconstruction was 52.4%. Clinical/pathological risk factors such as the pN stage, tumor differentiation, surgical margins, vascular invasion, perineural invasion, tumor recurrence significantly influenced the overall cumulative survival rate.
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10.1016/j.jormas.2020.12.003
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pubmed_936_3447
|
Volatile organic compounds (VOCs) in biological samples have gained popularity for disease monitoring and diagnosis. Celiac disease (CD) is one of the many prevalent health conditions which are challenging to diagnose. The aim of this study was to optimize a solid phase microextraction followed by gas chromatography-mass spectrometry, for quantitative analysis of a wide range of VOCs in the urine of patients with CD. Multivariate design of experiment was used to optimize the extraction conditions for the analysis of 15 urinary VOCs. Based on the performed experiments, extraction using 2.98 g of sodium chloride and 21 μL of 6 M hydrochloric acid for 15 min at 30 °C, using a CAR/PDMS fiber in headspace mode was found to be the most effective procedure for the analysis of the selected biomarkers. It was also demonstrated that the proposed method could distinguish between children with CD and healthy children based on the profile of VOCs. It is believed that quantitative analysis of these biomarkers will extend our understanding of CD and could be used for monitoring in patients under treatment.
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10.1039/c8ra07342b
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pubmed_156_1603
|
The Charadrii (shorebirds, gulls and alcids) are one of the most diverse avian groups from the point of view of sexual size dimorphism, exhibiting extremes in both male-biased and female-biased dimorphism, as well as monomorphism. In this study we use phylogenetic comparative analyses to investigate how size dimorphism has changed over evolutionary time, distinguishing between changes that have occurred in females and in males. Independent contrasts analyses show that both body mass and wing length have been more variable in males than in females. Directional analyses show that male-biased dimorphism has increased after inferred transitions towards more polygynous mating systems. There have been analogous increases in female-biased dimorphism after transitions towards more socially polyandrous mating systems. Changes in dimorphism in both directions are attributable to male body size changing more than female body size. We suggest that this might be because females are under stronger natural selection constraints related to fecundity. Taken together, our results suggest that the observed variation in dimorphism of Charadrii can be best explained by male body size responding more sensitively to variable sexual selection than female body size.
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10.1046/j.1420-9101.2003.00595.x
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pubmed_1001_18624
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Prostate cancer is the most predominant cancer in men and prostate cancer related death increases every year. Till date, there is no effective therapy other than androgen ablation therapy. At this stage, induction of apoptosis is considered as a better strategy to control cancer. Previous studies reported that aged garlic extract suppresses cancer growth and enhances immune system against cancer. In the present study, diallyl disulfide, oil soluble organosulfur compound of garlic, was studied for its antiproliferative effect on prostate cancer cells in vitro. The suppression of cell growth was demonstrated by [(3)H]thymidine incorporation assay. Induction of DNA damage was assessed by agarose gel electrophoresis. The results showed that diallyl disulfide inhibited the growth of prostate cancer cells in a dose dependent manner, compared to the control. At 50 microM and 100 microM concentrations, diallyl disulfide induced DNA damage in PC-3 cells. It is concluded that diallyl disulfide, component of aged garlic extract, inhibits proliferation of prostate cancer cells through the induction of apoptosis.
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10.1248/bpb.28.740
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pubmed_289_5036
|
Population ageing is occurring in China at a breathtaking pace and rapidly becoming a major public health issue. Due to the one-child policy, rural/urban migration and other societal changes, the family-dependent long-term care (LTC) of the past will no longer suffice. Barely existent now, both institutional and community-based services will need to expand to meet the growing need. China is still at an earlier stage in economic development and will be challenged to build these services and train staff. Furthermore, many elders are not yet covered by financial and insurance support. This massive demographic transition requires political efforts to develop integrated and sustainable national LTC systems.
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10.1080/17441692.2013.782060
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pubmed_316_3570
|
Hepatoblastoma is a rare hepatic tumor generally presenting during the first three years of life as an enlarging abdominal mass. Other symptoms are nonspecific; however, it may be associated with hemihypertrophy, virilization, and osteoporosis. The serum bilirubin infrequently is elevated, but up to 2/3's will have elevated serum alpha fetoprotein as a tumor marker. The overall survival rate is 35% in survivors who underwent a complete resection.
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10.1097/00003072-198612000-00023
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pubmed_568_19512
|
BACKGROUND
Aldehyde dehydrogenase 2 (ALDH2) plays an important role in the endogenous aldehyde detoxification of various types of cells. ALDH2*2, a variant allele of the ALDH2 polymorphism rs671, leads to decreased enzymatic activity. ALDH2*2 may enhance tumor antigen presentation due to aldehyde-induced DNA damage while suppressing peripheral blood T cell counts and T cell activation.
METHODS
On the basis of our hypothesis that rs671 affects the sensitivity of immune checkpoint inhibitors (ICIs), we evaluated the effects of rs671 on patients with thoracic malignancies who started ICI therapy in 2016-2019. The cohort consisted of 105 cases, including 64 cases with adenocarcinoma and 30 cases with squamous cell carcinoma, 49 of whom were ALDH2*2 carriers. The first ICI was PD-1/PD-L1 inhibitor (Nivolumab, Pembrolizumab, or Atezolizumab) in all cases.
RESULTS
The best response to anti-PD-1/PD-L1 therapy (partial response/stable disease/progressive disease) was 36%/50%/14% in the rs671(-) cases; however, the response was relatively poor in the rs671(+) cases (27%/29%/45%, respectively) (p = 0.002). The hazard ratio (95% confidence interval) of disease progression within the observation period of 6 months for the rs671(+) cases was estimated to be 5.0 (2.5-10) after the adjustment for covariates, including sex, Brinkman index, treatment line, tumor tissue programmed death-ligand 1 positivity rate, tumor tissue EGFR mutation. This association was also maintained in a stratified analysis, suggesting that ALDH2*2 is an independent negative predictive factor for the short-term prognosis of anti-PD-1/PD-L1 therapy. Thus, the progression-free survival (PFS) ratio of the rs671(+) cases decreased rapidly after ICI initiation but was eventually higher than that of the rs671(-) cases (restricted mean survival time in 12 months from 2 to 3 years afterward was 1.3 times that of the rs671(-) cases). Moreover, the highest PFS ratio after 2 years among sub-groups was found in the first-line treatment sub-group of rs671(+) group (40%).
CONCLUSIONS
Our study suggests that rs671 may be an accurate and cost-effective predictor of PD-1/PD-L1 inhibitor treatment, in which optimal case selection is an important issue.
|
10.1186/s12885-021-08329-y
|
pubmed_1066_22005
|
BACKGROUND
Evidence suggests that changes in dietary acid load may influence body weight, body composition, and insulin sensitivity.
METHODS
Participants (n = 244) were randomly assigned to an intervention (vegan) (n = 122) or control group (n = 122) for 16 weeks. Before and after the intervention period, body composition was measured by dual X-ray absorptiometry. Insulin resistance was assessed with the Homeostasis Model Assessment (HOMA-IR) index and predicted insulin sensitivity index (PREDIM). Repeated measure ANOVA was used for statistical analysis.
RESULTS
Potential Renal Acid Load (PRAL) and Net Endogenous Acid Production (NEAP) decreased significantly in the vegan group with no change in the control group (treatment effect -24.7 mEq/day [95% CI -30.2 to -19.2]; p < 0.001; and -23.8 mEq/day [95% CI -29.6 to -18.0]; p < 0.001, respectively). Body weight decreased by 6.4 kg in the vegan group, compared with 0.5 kg in the control group (treatment effect -5.9 kg [95% CI -6.8 to -5.0]; Gxt, p < 0.001), largely due to a reduction in fat mass and visceral fat. HOMA-IR index decreased and PREDIM increased in the vegan group. After adjustment for energy intake, changes in PRAL and NEAP correlated positively with changes in body weight (r = +0.37; p < 0.001; and r = +0.37; p < 0.001, respectively), fat mass (r = +0.32; p < 0.001; and r = +0.32; p < 0.001, respectively), visceral fat (r = +0.19; p = 0.006; and r = +0.15; p = 0.03, respectively), and HOMA (r = +0.17; p = 0.02; and r = +0.20; p = 0.006, respectively), and negatively with changes in PREDIM (r = -0.22; p = 0.002; and r = -0.27; p < 0.001, respectively).
CONCLUSION
Dietary acid load as part of a plant-based diet was associated with changes in body weight, body composition, and insulin sensitivity, independent of energy intake. Mechanistic explanations suggest that the relationship may be causal.
TRIAL REGISTRATION
ClinicalTrials.gov number, NCT03698955.
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10.1016/j.clnesp.2021.05.015
|
pubmed_716_3347
|
Alternative non-B-DNA conformations formed under physiological conditions by sequences called flipons include left-handed Z-DNA, three-stranded triplexes, and four-stranded i-motifs and quadruplexes. These conformations accumulate and release energy to enable the local assembly of cellular machines in a context specific manner. In these transactions, nucleosomes store power, serving like rechargeable batteries, while flipons smooth energy flows from source to sink by acting as capacitors or resistors. Here, I review the known biological roles for flipons. I present recent and unequivocal findings showing how innate immune responses are regulated by Z-flipons that identify endogenous RNAs as self. Evidence is also presented supporting important roles for other flipon classes. In these examples, the dynamic exchange of energy between flipons and nucleosomes enables rapid switching of genetic programs without altering flipon sequence. The increased phenotypic diversity enabled by flipons drives their natural selection, with adaptations evolving faster than is possible by codon mutation alone.
|
10.1002/bies.202200166
|
pubmed_191_6906
|
The effect of the antifungal drug bifonazole on Ca2+ homeostasis in Madin Darby canine kidney (MDCK) cells was investigated. Cell suspensions were loaded with the Ca2+-sensitive dye fura-2, and the fluorescence changes were measured with a spectrofluorophotometer. At concentrations between 10-80 microM bifonazole increased cytosolic free Ca2+ levels ([Ca2+]i) in a concentration-dependent manner. The Ca2+ signals were partly inhibited by removing extracellular Ca2+. Bifonazole (40 microM) released Ca2+ from the store sensitive to 1 microM thapsigargin, an endopolasmic reticulum Ca2+ pump inhibitor. Bifonazole (40 microM) per se induced capacitative Ca2+ entry while reduced 1 microM thapsigargin-induced capacitative Ca2+ entry. Inositol 1,4,5-trisphosphate may be involved in bifonazole-induced Ca2+ release because inhibiting phospholipase C with 2 microM U73122 partly reduced the bifonazole response. Together, bifonazole increased [Ca2+]i in renal tubular cells by inducing intracellular Ca2+ release and extracellular Ca2+ influx.
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pubmed_191_6906
|
pubmed_288_9539
|
The objective of the study was to assess the effect of temperature on the extent of aerobic batch biodegradation of potato stillage with a mixed culture of bacteria of the genus Bacillus. The experiments were performed in a 5-l stirred-tank reactor at 20, 30, 35, 40, 45, 50, 55, 60, 63 and 65 degrees C with the pH of 7. Only at 65 degrees C, no reduction in chemical oxygen demand (COD) was found to occur. Over the temperature range of 20-63 degrees C, the removal efficiency was very high (with an extent of COD reduction following solids separation that varied between 77.57% and 89.14% after 125 h). The process ran at the fastest rate when the temperature ranged from 30 to 45 degrees C; after 43 h at the latest, COD removal amounted to 90% of the final removal efficiency value obtained for the process. At 20, 55, 60 and 63 degrees C, a 90% removal was attained after 80 h. Two criteria were proposed for the identification of the point in time when the process is to terminate. One of these consists in maximising the product of the extent of COD reduction and the extent of N-NH4 content reduction. The other criterion is a simplified one and involves the search for the minimal value of N-NH4 concentration.
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10.1016/j.biortech.2008.01.063
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pubmed_293_21212
|
Background: Equine maxillary cheek teeth infundibulae are frequently affected by developmental and acquired disorders, but the imaging, gross, and histological features of normal and abnormal infundibulae remain incompletely understood. Objective: To perform MicroCT, gross examination, and histology on sectioned teeth and compare the imaging and anatomical findings. Study design: Ex vivo original study. Methods: Eight maxillary cheek teeth of different ages and with varying grades of unilateral (n = 5) or bilateral (n = 3) occlusal infundibular caries were extracted from equine heads obtained from an abattoir. The teeth were imaged by MicroCT, then transversely sectioned and grossly and histologically examined, with the imaging and gross and histological anatomical findings examined and compared. Results: Fifteen infundibulae, including two without occlusal caries had subocclusal cemental hypoplasia or caries. One infundibulum without occlusal caries had no subocclusal cemental defects. Histologically, hypoplastic cemental areas consisted of irregularly-shaped, wide central channels, with multiple, large, cylindrical side-branches that extended peripherally to a variable extent. Cementum with extensive, wide, empty channels, and cementum with a more irregular moth-eaten appearance had dark or eroded gross appearance and a low HU on CT. Some infundibulae had cement-free areas that only contained fragments of collagen-like material, especially at their apical aspects (apical cemental hypoplasia). Carious subocclusal areas had connections with the occlusal surface and had disrupted cemental architecture, including of their central vascular channel that, along with their side branches, contained degraded food, and cemental debris. Main Limitations: No clinical histories or accurate ages were available for these eight teeth. Conclusions: Hypoplastic cemental lesions, including at central linear and apical sites, histologically contain areas with multiple wide-branched, cylindrical channels or even areas of total cement hypoplasia visible on gross sections When such cemental defects contact the occlusal surface due to normal wear, food impaction, and caries can ensue.
|
10.3389/fvets.2019.00125
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pubmed_635_21441
|
BACKGROUND
The decline in the incidence of stillbirths in Germany has remained static in recent years. This study aims to analyse the current situation of data documentation and examination of stillbirths. Furthermore, possible stillbirth prevention strategies should be developed.
METHODS
Searches in the international peer-reviewed literature, retrospective data collection of 168 stillbirths in 8 hospitals, (in the area of Bonn) with subsequent statistical evaluation (descriptive statistics, t-test and binominal test) were undertaken.
RESULTS
This study shows considerable deficits in data documentation, interdisciplinary communication and postmortal examination. Only in 51.8% (87/168) of the cases was a certain or uncertain cause of death found (42.3% placental, 1.2% foetal, 3.6% chromosomal, 4.8% umbilical cord abnormalities). Severe foetal growth restriction (<5(th) percentile) was observed in 29.2%; 44.9% (22/49) of them died at the age of ≥36+0 weeks of gestation.
CONCLUSION
The first step to reduce the rate of stillbirths in Germany is to increase the identified causes of foetal death: Therefore, an interdisciplinary case report form was compiled to improve data collection and interdisciplinary collaboration. To standardise and complete postmortal management, an algorithm was created. The long-term aim is the development of a central data register for statistical analysis, to identify goals of research and to organise conferences with interdisciplinary reports of diagnostic findings.
|
10.1055/s-0034-1395654
|
pubmed_1128_2722
|
The main glycophospholipid of Thermoplasma acidophilum, grown at 39 degrees C, is composed of a di-isopranol-2,3-glycerotetraether. It has been characterized in hydrated systems by calorimetry. Unlike its equivalent grown at 59 degrees C, it shows complex phase properties, which include at least three different phases, (1) a liquid-analogue state (C), which is stable above 20 degrees C, (2) a metastable solid-analogue state (A) formed by supercooling of the liquid-analogue state (C) and (3) a stable solid-analogue state (B), which is slowly formed and may include a close chain packing of lipids and a network of hydrogen bonds between the headgroups. A high fraction of acyclic isopranol chains seems to be a prerequisite for the formation of state (B). A phase diagram, displaying the observed states and the transitions between them is proposed.
|
10.1016/0005-2736(90)90208-6
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pubmed_222_18513
|
OBJECTIVE
To determine whether increased immunosuppression is a contributor to poor outcome in hepatitis C-infected orthotopic liver transplant (OLT) recipients, we retrospectively analyzed the consequences of using OKT3 in our program for steroid-resistant rejection (SRR).
METHODS
We compared the histological recurrence of HCV in two contemporary cohorts of OLT recipients. Group 1 consisted of HCV-positive patients who received OKT3 for SRR (n = 19). Group 2 (n = 33) consisted of age-, gender-, and initial immunosuppression-matched HCV-positive controls who were treated with at least one steroid pulse for acute cellular rejection but who did not require treatment with OKT3. Liver biopsies were obtained per protocol within the first month and as necessary to evaluate abnormalities in serum liver chemistries.
RESULTS
Mean and median follow-up were comparable for the two groups. Recurrence of HCV was diagnosed by histological verification and was documented in 16 of 19 (84.2%) group 1 patients versus 17 of 33 (51.5%) group 2 patients (p = 0.03). The interval to recurrence was significantly shorter in patients who received OKT3 (p = 0.028). Logistic regression identified OKT3 as a significant risk factor for the recurrence of HCV within the first year post-OLT (p = 0.0004). The histological severity score, based on the most recent liver biopsy at long-term follow-up or the explant biopsy if the patient required retransplantation, was significantly higher in group 1. Moreover, cirrhosis was demonstrable in a greater proportion of allografts in patients who had received OKT3 at some point (26.3% vs. 6%, p = 0.028). Long-term follow-up revealed a trend toward higher alanine aminotransferase levels (p = 0.05) and total bilirubin (p = 0.08) in group 1 patients.
CONCLUSIONS
Our data suggest that allograft hepatitis in patients with preexisting HCV occurs earlier and with greater severity in patients treated with OKT3 for SRR, compared with age-, gender-, and initial immunosuppression-matched contemporary controls. Treatment of SRR with OKT3 may jeopardize long-term allograft function and survival in HCV-infected recipients by enhancing viral hepatitis recurrence. Clearly, the recognition of recurrent HCV and differentiation from acute cellular rejection remains a crucial issue in managing the OLT recipient with HCV.
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pubmed_222_18513
|
pubmed_764_5389
|
Radiolabeling of [Tyr8]-substance P ([Tyr8]-SP) with the (125)I-isotope was performed by use of the chloramine-T technique. The primary formed radiolabeled product, having been quantitatively converted to the corresponding sulfoxide yielding [(125)I]-[Tyr8]-(Met11-->O)-SP completely lacked any binding to proteins rich in SP receptor populations. However, after reductive treatment with mercaptoethanol for about 2 h, a complete reconstitution of the Met11 thioether structure was observed. The reduced peptide, consisting of [(125)I]-[Tyr8]-(Met11)-SP was separated from its by-products by reversed-phase high-performance liquid chromatography on octadecylsilyl silica gel with 100 mM triethyl ammonium formate buffer containing 22% acetonitrile (pH 2.2). The labeled SP derivative prepared by this two-step synthesis was obtained in 73% overall yield related to the [Tyr8]-SP starting material and exhibited a specific activity of 1.9-10(6) Ci/M. In contrast to [(125)I]-[Tyr8]-->(Met11-->O)-SP, satisfactory receptor-binding was now observed with the [(125)I]-->[Tyr8]-(Met11)-SP derivative.
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10.1016/s0378-4347(97)00278-8
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pubmed_1108_10900
|
BACKGROUND/AIMS
The aim of this study was to clarify the role of the additional Hassab's operation to hepatectomy in cirrhotic patients with resectable hepatocellular carcinomas and esophagogastric varices.
METHODOLOGY
Subjects were 36 cirrhotic patients with hepatocellular carcinomas and concomitant esophagogastric varices: 20 underwent hepatectomy alone (non-Hassab group) and 16 underwent hepatectomy with Hassab's operation (Hassab group).
RESULTS
Patients in the Hassab group had more advanced esophageal varices and the accompanied gastric varices, preoperatively (p<0.01). Both preoperative platelet counts (p<0.01) and prothrombin time (p<0.05) were significantly lower in the Hassab group, and serum albumin level also tended to be worse than those in the non-Hassab group. Portal pressure was significantly higher in the Hassab group (p<0.01). Despite these disadvantages, no significant differences were found in operative mortality, postoperative courses and long-term prognosis between the two groups. Comparing the cause of death, the incidence of the fatal variceal hemorrhage was significantly lower (0%) in the Hassab group than that (25%) in the non-Hassab group (p<0.05).
CONCLUSIONS
This study suggested that additional Hassab's operation to hepatectomy might have reduced the risk of variceal hemorrhage after hepatectomy.
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pubmed_1108_10900
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pubmed_591_2604
|
BACKGROUND
The present study was conducted to assess gender difference in the relationship between the ferritin and homeostasis model assessment of insulin resistance (HOMA-IR) and beta cell function (HOMA-B) in non-diabetic Korean adults.
MATERIALS AND METHODS
A sample including 5,414 adults (2,279 men, 1,529 postmenopausal women, and 1,606 premenopausal women) aged ≥ 20 years from the fifth Korean National Health and Nutrition Examination Survey (KNHANES V-1, 2010) was analyzed.
RESULTS
There were several key findings in the present study. First, in men, HOMA-IR (β = 0.119, 95% confidence interval [CI], 3.304 to 8.003) constituted the independent factor determining ferritin, but this was not the case for HOMA-B (β = -0.042, 95% CI, -0.100 to 0.011). Second, in postmenopausal women, HOMA-IR (β = 0.087, 95% CI, 0.899 to 5.238) was the independent factor determining ferritin, but this was not the case for HOMA-B (β = -0.043, 95% CI, -0.065 to 0.010). Third, in premenopausal women, neither HOMA-IR (β = -0.050, 95% CI, -3.056 to 0.364) nor HOMA-B (β = -0.009, 95% CI, -0.028 to 0.020) constituted the independent factors determining ferritin.
CONCLUSIONS
Ferritin was positively associated with insulin resistance in non-diabetic Korean men and postmenopausal women, but not in non-diabetic Korean premenopausal women.
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10.1371/journal.pone.0199465
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pubmed_1124_4091
|
Addition of pseudorabies virus (PrV)-specific polyclonal immunoglobulins to PrV-infected monocytes induces internalization of plasma membrane anchored viral glycoproteins. This process may interfere with antibody-dependent cell lysis and resembles the well-studied physiological endocytosis process. A confocal study was designed to investigate whether the major cellular components, involved in physiological endocytosis (clathrin, actin, dynein and microtubules), play a role in this virological internalization process. In order to visualize the interaction of endosomes, which contain the internalized viral glycoproteins, with clathrin, actin, dynein and microtubules, a double labeling of viral glycoproteins and different cellular proteins was performed. Porcine monocytes were inoculated with the PrV-strain 89V87 at a multiplicity of infection of 50 for 13h. After the addition of FITC-labeled porcine polyclonal PrV-specific antibodies, cells were fixed with para-formaldehyde at different time points and afterwards permeabilized. The different cellular components were visualized with monoclonal antibodies and a Texas Red-conjugate, with the exception of actin, which was stained with phalloidin-Texas Red. The cells were analyzed by confocal microscopy. A clear co-localization was observed between the viral glycoproteins and clathrin and dynein during the internalization process. The microtubules were in close contact with the internalized vesicles. For actin no co-localization could be observed. It can be stated that clathrin, dynein and microtubules, important components during physiological endocytosis, are also of importance during the antibody-induced internalization of viral glycoproteins.
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10.1016/s0378-1135(01)00490-4
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pubmed_1114_21511
|
Substance use and/or disorders (SUDs) have been identified as a significant correlate of intimate partner violence (IPV) exposure and present complex issues that intersect with the topography of IPV, attendant mental health, and physical co-morbidities and may pose barriers to primary care- and other agency-based screening and intervention efforts. Despite substantial research indicating significantly higher rates of all types and severity of IPV victimization among women with SUDs and bidirectional associations between partner or self-use of drugs or alcohol and IPV victimization, effective screening, brief interventions, coordinated systems of care, and treatment approaches to address these co-occurring problems remain very limited. We integrated select research examining the intersection of IPV victimization and SUDs and several comorbidities that have significant public health impact and provided recommendations for scaling up targeted interventions to redress these co-occurring problems among women in primary, emergency, and other care settings.
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10.1089/jwh.2014.4866
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pubmed_573_10387
|
Readily available 1-mesyl-1,2,3-triazoles are efficiently converted into a variety of imidazolones and thiazoles by Rh(II)-catalyzed denitrogenative reactions with isocyanates and isothiocyanates, respectively. The proposed triazole-diazoimine equilibrium results in the formation of highly reactive azavinyl metal-carbenes, which react with heterocumulenes causing an apparent swap of 1,2,3-triazole core for another heterocycle.
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10.1021/ja400350c
|
pubmed_896_7165
|
Cholangiocarcinoma (CCA) results from the malignant transformation of cholangiocytes. Primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC) are chronic diseases in which cholangiocytes are primarily damaged. Although PSC is an inflammatory condition predisposing to CCA, CCA is almost never found in the autoimmune context of PBC. Here, we hypothesized that PBC might favor CCA immunosurveillance. In preclinical murine models of cholangitis challenged with syngeneic CCA, PBC (but not PSC) reduced the frequency of CCA development and delayed tumor growth kinetics. This PBC-related effect appeared specific to CCA as it was not observed against other cancers, including hepatocellular carcinoma. The protective effect of PBC was relying on type 1 and type 2 T cell responses and, to a lesser extent, on B cells. Single-cell TCR/RNA sequencing revealed the existence of TCR clonotypes shared between the liver and CCA tumor of a PBC host. Altogether, these results evidence a mechanistic overlapping between autoimmunity and cancer immunosurveillance in the biliary tract.
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10.1084/jem.20200853
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pubmed_894_6201
|
Behavioral and cardiorespiratory responses to a lethal dose of morphine were evaluated in rats pretreated with saline or naloxazone, an antagonist of high-affinity mu 1 opioid receptors. Pretreatment with naloxazone significantly blocked morphine analgesia, catalepsy and hypothermia at a dose which completely eliminated high-affinity binding in brain membranes. Moreover, naloxazone significantly attenuated the morphine-induced hypotension and respiratory depression, whereas morphine-induced bradycardia was less affected. Results indicate that subpopulations of mu receptors may mediate selective behavioral and cardiorespiratory responses to morphine.
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10.1016/0304-3940(83)90153-2
|
pubmed_160_17055
|
INTRODUCTION/OBJECTIVES
The effect of parental brain injury on children has been relatively little investigated. This study examines post-traumatic stress symptoms (PSS) and psychological functioning in children with a parent with an acquired brain injury.
PARTICIPANTS, MATERIALS AND METHODS
The participants were 35 patients with acquired brain injury, their spouses and children aged 7-14 years recruited from out-patient brain injury rehabilitation units across Denmark. Children self-reported psychological functioning using the Becks Youth Inventory (BYI) and Child Impact of Events revised (CRIES) measuring PSS symptoms. Emotional and behavioural problems among the children were also identified by the parents using the Achenbach's Child Behaviour Checklist (CBCL). A matched control group, consisting of 20 children of parents suffering from diabetes, was recruited from the National Danish Diabetes Register.
RESULTS
Post-traumatic stress symptoms above cut-off score (<30) were found (CRIES) in 46% of the children in the brain injury group compared to 10% in the diabetes group. The parents in the brain injury group reported more emotional and behavioural problems in their children when compared to published norms (CBCL).
CONCLUSIONS
When parents have acquired brain injury, their children appear to be at a substantial risk for developing post-traumatic stress symptoms. These results indicate the need for a child-centred family support service to reduce the risk of children being traumatized by parental brain injury, with a special focus on the relational changes within the family.
|
10.3109/02699052.2011.579933
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pubmed_811_509
|
Healthy adult dogs were subjected to stepwise reduction of nephron population so as to create the transition from normal renal function to advanced renal insufficiency. Studies were performed at each level of renal function. Glomerular filtration rate (GFR), renal phosphate clearance, and serum radioimmunoassayable parathyroid hormone (PTH) levels were measured. Two groups of animals were studied. In one, phosphorous intake was maintained at 1200 mg/day. As GFR declined, fractional phosphate excretion rose reciprocally, and PTH levels increased over 20-fold. In the second group, phosphorous intake was maintained at less than 100 mg/day. As GFR fell, fractional phosphate excretion changed little, and no increment in PTH levels occurred. The data suggest that the control system regulating phosphate excretion contributes importantly to the pathogenesis of secondary hyperparathyroidism in advancing renal insufficiency.
|
10.1172/JCI106517
|
pubmed_877_22868
|
The aim of this work was to analyze a shrouded impeller pediatric ventricular assist device (SIP-VAD). This device has distinctive design characteristics and parameter optimizations for minimization of recirculation flow and reduction in high-stress regions that cause blood damage. Computational Fluid Dynamics (CFD) simulations were performed to analyze the optimized design. The bench-top prototype of SIP-VAD was manufactured with biocompatible stainless steel. A study on the hydrodynamic and hemodynamic performance of the SIP-VAD was conducted with predictions from CFD and actual experimentation values, and these results were compared. The CFD analysis yielded a pressure range of 29-90 mmHg corresponding to flow rates of 0.5-3 L/min over 9000-11000 rpm. The predicted value of the normalized index of hemolysis (NIH) was 0.0048 g/100 L. The experimental results with the bench-top prototype showed a pressure rise of 30-105 mmHg for the flow speed of 8000-12000 rpm and flow rate of 0.5-3.5 L/min. The maximum difference between CFD and experimental results was 4 mmHg pressure. In addition, the blood test showed the average NIH level of 0.00674 g/100 L. The results show the feasibility of shrouded impeller design of axial-flow pump for manufacturing the prototype for further animal trials.
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10.1007/s10047-018-1028-3
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pubmed_543_12520
|
In this study, we evaluated the feet of 144 consecutive children with juvenile rheumatoid arthritis (JRA) during a routine outpatient visit to discover patterns of foot problems. We found that all but nine subjects had at least 1 of 21 foot problems, categorized as inflammation, limitation of motion, and abnormal alignment. Overall, pronated rearfoot and midfoot were observed in 73% and 72% of JRA patients, respectively. Additionally, 36% had splayfoot, whereas 35% of subjects had ankle limitation of motion. Other common foot problems included pronated forefoot, rearfoot and forefoot synovitis, forefoot limitation of motion, and toe valgus. Significant differences in the occurrence of various foot problems were observed among JRA onset/course subgroups and were influenced by both age and disease duration. Specifically, subjects with polyarticular JRA had more forefoot limitation and toe valgus, whereas subjects with pauciarticular JRA had pronated forefoot more often. Ankle limitation of motion, although unrelated to the JRA sub-group, was related to the duration of JRA. Subjects with longer disease histories also had toe valgus more often. Conversely, forefoot limitation of motion seemed to be more a function of age than of disease duration. These results indicate that foot problems are common in the JRA population, and they underscore the need for thorough evaluation and physical therapy management.
|
10.1002/art.1790070308
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pubmed_54_16612
|
INTRODUCTION
Micro-RNA, a new class of small, non-coding RNAs, have been shown to be deregulated in several human carcinomas. In particular, SNP rs2910164 in pre-miR146a appears to be correlated with papillary thyroid carcinoma and may be involved in its genetic predisposition. Since data on follicular thyroid carcinomas (FTC) are lacking, we evaluated the involvement of SNP rs2910164 in FTC.
METHODS
Thirty-nine cases of FTC and 20 follicular adenomas, defined according to WHO criteria, were selected. DNA and RNA were extracted from formalin-fixed paraffin-embedded blocks of both neoplastic and non-neoplastic areas. The DNA region of pre-miR146a, containing SNP rs2910164, was sequenced. Total RNA including miRNAs was used for stem-loop RT reactions, and applying a standard TaqMan PCR kit protocol for real-time PCR. Wilcoxon signed-rank test and Friedman test were used for statistical analyses.
RESULTS
In 31% of FTC, the G allele was observed in neoplastic tissues, compared with the non-neoplastic areas (p < 0.05), whereas the CC phenotype was completely absent in tumours. Moreover, the expression of pre-miR146a was found to be significantly down-regulated in neoplastic tissues from FTC cases (p = 0.043), although no significant differences were seen in follicular thyroid adenomas.
DISCUSSION
The expression profile of pre-miR146a can be correlated with FTC tumourigenesis. The G allele in SNP rs2910164 appears to be correlated with the transition from normal to neoplastic tissue. The GG and GC alleles appear to be associated with an increased risk for FTC, while the CC allele seems to play a protective role.
|
pubmed_54_16612
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pubmed_398_424
|
Previous freeze-fracture electron microscopy (EM) studies have shown that the outer membrane (OM) of Treponema pallidum contains sparse transmembrane proteins. One strategy for molecular characterization of these rare OM proteins involves isolation of T. pallidum OMs. Here we describe a simple and extremely gentle method for OM isolation based upon isopycnic sucrose density gradient ultracentrifugation of treponemes following plasmolysis in 20% sucrose. Evidence that T. pallidum OMs were isolated included (i) the extremely low protein/lipid ratio of the putative OM fraction, (ii) a paucity of antigenic and/or biochemical markers for periplasmic, cytoplasmic membrane, and cytosolic compartments, and (iii) freeze-fracture EM demonstrating that the putative OMs contained intramembranous particles highly similar in size and density to those in native T. pallidum OMs. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis revealed that the OMs contained a relatively small number of treponemal proteins, including several which did not appear to correspond to previously characterized T. pallidum antigens. Interestingly, these candidate rare OM proteins reacted poorly with syphilitic sera as determined by both conventional immunoblotting and enhanced chemiluminescence. Compared with whole cells, T. pallidum OMs were deficient in cardiolipin, the major lipoidal antigen reactive with antibodies in syphilitic sera. Also noteworthy was that other lipoidal constituents of OMs, including the recently discovered glycolipids, did not react with human syphilitic sera. These latter observations suggest that the poor antigenicity of virulent T. pallidum is a function of both the lipid composition and the low protein content of its OM.
|
10.1128/iai.63.11.4244-4252.1995
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pubmed_290_14923
|
The pineal gland is a naturally calcifying endocrine organ which secretes the sleep-promoting hormone melatonin. Age-related changes of the pineal have been observed, including decreased pinealocyte numbers, increased calcification, and a reduction in melatonin production. Since fluoride is attracted to calcium within the pineal gland, this study sought to examine the effects of a fluoride-free diet on the morphology of the pineal gland of aged male rats (26 months old). All animals had previously been raised on standard fluoridated food and drinking water. These control animals were compared to other animals that were placed on a fluoride-free diet ("fluoride flush") for 4 or 8 weeks. At 4 weeks, pineal glands from fluoride-free animals showed a 96% increase in supporting cell numbers and at 8 weeks a 73% increase in the number of pinealocytes compared to control animals. In contrast, the number of pinealocytes and supporting cells in animals given an initial 4-week fluoride flush followed by a return to fluoridated drinking water (1.2 ppm NaF) for 4 weeks were not different from control animals. Our findings therefore demonstrate that a fluoride-free diet encouraged pinealocyte proliferation and pineal gland growth in aged animals and fluoride treatment inhibited gland growth. These findings suggest that dietary fluoride may be detrimental to the pineal gland.
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10.1007/s12011-019-01964-4
|
pubmed_454_6592
|
Recent studies suggest that vitamin D may be associated with reduced breast cancer risk, but most studies have evaluated only dietary vitamin D intake. The associations among ultraviolet radiation from sunlight, factors related to cutaneous vitamin D production, and breast cancer risk were evaluated in a population-based case-control study conducted in Ontario, Canada, between 2003 and 2004 (n = 3,101 cases and n = 3,471 controls). Time spent outdoors was associated with reduced breast cancer risk during 4 periods of life (>21 vs. ≤6 hours/week age-adjusted odds ratio (OR) = 0.71, 95% confidence interval (CI): 0.60, 0.85 in the teenage years; OR = 0.64, 95% CI: 0.53, 0.76 in the 20s-30s; OR = 0.74, 95% CI: 0.61, 0.88 in the 40s-50s; and OR = 0.50, 95% CI: 0.37, 0.66 in the 60s-74 years). Sun protection practices and ultraviolet radiation were not associated with breast cancer risk. A combined solar vitamin D score, including all the variables related to vitamin D production, was significantly associated with reduced breast cancer risk. These associations were not confounded or modified by menopausal status, dietary vitamin D intake, or physical activity. This study suggests that factors suggestive of increased cutaneous production of vitamin D are associated with reduced breast cancer risk.
|
10.1093/aje/kwr091
|
pubmed_1076_17870
|
BACKGROUND
Rotavirus is recognized as a significant cause of pediatric gastroenteritis worldwide. Comprehensive data on the burden of rotavirus disease in Europe were lacking.
METHODS
A prospective, multicenter, observational study was conducted during the 2004-2005 season in selected areas of Belgium, France, Germany, Italy, Spain, Sweden, and the United Kingdom, to estimate the incidence of acute gastroenteritis (AGE) and rotavirus gastroenteritis (RVGE) in children <5 years of age who require medical care in primary care, emergency department, and hospital settings.
RESULTS
A total of 2846 children with AGE were included in the study, and, of the 2712 children for whom ELISA results were available, 1102 (40.6%) were found to be rotavirus positive. The estimated annual incidence of RVGE was 2.07-4.97 cases/100 children <5 years of age, and it was highest among children 6-23 months of age, with 56.7%-74.2% of all RVGE cases occurring in children in this age group. Overall, RVGE was estimated to account for 27.8%-52.0% of AGE cases, and it was responsible for up to two-thirds of hospitalizations and emergency department consultations, as well as one-third of primary care consultations for AGE.
CONCLUSIONS
Rotavirus infections account for a significant proportion of AGE cases in children <5 years of age in Europe, many of whom require frequent primary care consultations or care in emergency department and/or hospital settings. The results of the present study suggest that routine rotavirus vaccination for infants <6 months of age could significantly reduce the substantial burden of this potentially serious childhood disease.
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10.1086/516714
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pubmed_489_23869
|
The typical symptoms of advanced cancer of the stomach are well known in clinical practice. The presented case concerns a patient with symptoms of left-sided renal colic, caused by a malignant tumour involving the ureter, which was diagnosed with a CT scan. The multifocal process, involving the stomach, two parts of the colon, the left ovary and the side of the pelvis, was confirmed only during surgery. The resection or partial resection of the above-mentioned organs involved by the malignant process and reconstruction of the alimentary tract as well as the ureter were performed at time of this operation. The patient's recovery was without any complications. The histopathological findings support the diagnosis of this malignant process as disseminated stomach cancer. In the available literature only two cases of stomach cancer metastasis to the ureter have been described. In both cited examples resection of the ureter with nephrectomy was performed. The review of the literature supports the value of stomach palliative resection in prolonging life and improving quality of life.
|
10.5114/wo.2012.28803
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pubmed_794_5019
|
Microalgae host varied microbial consortium harboring cross-kingdom interactions with fundamental ecological significance in aquatic ecosystems. Revealing the complex biofunctions of the cultivable bacteria of phycosphere microbiota is one vital basis for deeply understanding the mechanisms governing these dynamic associations. In this study, a new light-yellow pigmented bacterial strain LZ-28 was isolated from the highly-toxic and harmful algal bloom-forming dinoflagellate Alexandrium catenella LZT09. Collective phenotypic and genotypic profiles were obtained to confidently identify this strain as a new Mameliellaalba member. Comparative genomic analysis showed that strain LZ-28 shared highly similar functional features with other four marine algae-derived M. alba strains in spite of their distinctive isolation sources. Based on the bioactivity assaying, the mutual growth-promoting effects between bacterial strain LZ-28 and algal strain LZT09 were observed. After the culture conditions were optimized, strain LZ-28 demonstrated an extraordinary production ability for its bioflocculanting exopolysaccharides (EPS). Moreover, the portions of two monosaccharides glucose and fucose of the EPS were found to positively contribute to the bioflocculanting capacity. Therefore, the present study sheds light on the similar genomic features among the selected M. alba strains, and it also reveals the potential pharmaceutical, environmental and biotechnological implications of active EPS produced by this new Mameliella alba strain LZ-28 recovered from toxic bloom-forming marine dinoflagellate.
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10.3390/md20050321
|
pubmed_1090_17924
|
Resistance to intercalating dyes (ethidium, acriflavine) and other organic cations, such as quaternary ammonium-type antiseptic compounds, mediated by the Staphylococcus aureus plasmid pSK1 is specified by an energy-dependent export mechanism encoded by the qacA gene. From nucleotide sequence analysis, qacA is predicted to encode a protein of Mr 55017 containing 514 amino acids. The gene is likely to initiate with a CUG codon, and a 36 bp palindrome immediately preceding qacA, along with an upstream reading frame with homology to the TetR repressors, may be components of a regulatory circuit. The putative polypeptide specified by qacA has properties typical of a cytoplasmic membrane protein, and is indicated to be a member of a transport protein family that includes proteins responsible for export-mediated resistance to tetracycline and methylenomycin, and uptake of sugars and quinate. The analysis suggests that N- and C-terminal regions of these proteins are involved in energy coupling (proton translocation) and substrate transport, respectively. The last common ancestor of the qacA and related tet (tetracycline resistance) lineages is inferred to have been repressor controlled, as occurs for modern tet determinants from Gram-negative, but not those from Gram-positive, bacteria.
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10.1111/j.1365-2958.1990.tb00565.x
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pubmed_581_6714
|
To test the directness of factors in initiating PIWI-directed gene silencing, we employed a Piwi-interacting RNA (piRNA)-targeted reporter assay in Drosophila ovary somatic sheet (OSS) cells [1]. This assay confirmed direct silencing roles for piRNA biogenesis factors and PIWI-associated factors [2-12] but suggested that chromatin-modifying proteins may act downstream of the initial silencing event. Our data also revealed that RNA-polymerase-II-associated proteins like PAF1 and RTF1 antagonize PIWI-directed silencing. PAF1 knockdown enhances PIWI silencing of reporters when piRNAs target the transcript region proximal to the promoter. Loss of PAF1 suppresses endogenous transposable element (TE) transcript maturation, whereas a subset of gene transcripts and long-non-coding RNAs adjacent to TE insertions are affected by PAF1 knockdown in a similar fashion to piRNA-targeted reporters. Additionally, transcription activation at specific TEs and TE-adjacent loci during PIWI knockdown is suppressed when PIWI and PAF1 levels are both reduced. Our study suggests a mechanistic conservation between fission yeast PAF1 repressing AGO1/small interfering RNA (siRNA)-directed silencing [13, 14] and Drosophila PAF1 opposing PIWI/piRNA-directed silencing.
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10.1016/j.cub.2017.07.052
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pubmed_1013_1446
|
Males and females have been proposed to have different prenatal growth strategies, whereby males invest more in fetal growth and less in placental development, leaving them more susceptible to early-life adversity. We tested predictions of this hypothesis using data from the National Collaborative Perinatal Project. Male newborns were heavier than females, but there was no difference in placental weight, adjusting for birthweight. Among infants born prior to 33 weeks, the difference in birthweight between males and females was greater among those who did not survive than among those who did, potentially reflecting a strategy whereby males maintained growth in the face of prenatal insults, while females adjusted growth. However, there was no significant difference in mortality between the sexes. Being born small-for-gestational age or very preterm (prior to 33 weeks) was associated with significantly reduced performance for most of the cognitive traits examined at 7 years, although maternal preeclampsia was associated with reduced performance in fewer traits. Generally, these effects of early-life adversity (poor fetal growth, prematurity, and preeclampsia) did not differ between the sexes. However, analyzing the sexes separately (rather than testing the interaction between sex and adversity) resulted in numerous spurious sex-specific effects, whereby the effect of early-life adversity appeared to be significant in one sex but not the other. Overall, we found little support for the hypothesis that males prioritize growth more than females, and that this makes them more susceptible to early-life adversity. Furthermore, our results show that analyzing the sexes separately, rather than testing the adversity by sex interaction, can be highly misleading.
|
10.1017/S2040174422000204
|
pubmed_643_14626
|
Fetal sheep with placental insufficiency-induced intrauterine growth restriction (IUGR) have lower fractional rates of glucose oxidation and greater gluconeogenesis, indicating lactate shuttling between skeletal muscle and liver. Suppression of pyruvate dehydrogenase (PDH) activity was proposed because of greater pyruvate dehydrogenase kinase (PDK) 4 and PDK1 mRNA concentrations in IUGR muscle. Although PDK1 and PDK4 inhibit PDH activity to reduce pyruvate metabolism, PDH protein concentrations and activity have not been examined in skeletal muscle from IUGR fetuses. Therefore, we evaluated the protein concentrations and activity of PDH and the kinases and phosphatases that regulate PDH phosphorylation status in the semitendinosus muscle from placenta insufficiency-induced IUGR sheep fetuses and control fetuses. Immunoblots were performed for PDH, phosphorylated PDH (E1α), PDK1, PDK4, and pyruvate dehydrogenase phosphatase 1 and 2 (PDP1 and PDP2, respectively). Additionally, the PDH, lactate dehydrogenase (LDH), and citrate synthase (CS) enzymatic activities were measured. Phosphorylated PDH concentrations were 28% lower (P < 0.01) and PDH activity was 67% greater (P < 0.01) in IUGR fetal muscle compared with control. PDK1, PDK4, PDP1, PDP2, and PDH concentrations were not different between groups. CS and LDH activities were also unaffected. Contrary to the previous speculation, PDH activity was greater in skeletal muscle from IUGR fetuses, which parallels lower phosphorylated PDH. Therefore, greater expression of PDK1 and PDK4 mRNA did not translate to greater PDK1 or PDK4 protein concentrations or inhibition of PDH as proposed. Instead, these findings show greater PDH activity in IUGR fetal muscle, which indicates that alternative regulatory mechanisms are responsible for lower pyruvate catabolism.
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10.1152/ajpregu.00106.2019
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pubmed_620_4596
|
Population-genetic investigation was carried out in the regions endemic for Viljuisk encephalomyelitis (VE). The following indices were estimated: the relationship coefficient, the inbreeding coefficient, the intensity of migration, genetic structure of the population. The aim of the investigation was to explain causes of intrapopulational and, in some cases, of intragenus accumulation of the VE patients. No evidence of isolation or increased inbreeding were found in highly affected populations. The genetic structure of a group of VE patients tested for 9 polymorphic systems did not reveal any deviation from the control group. Several VE cases in healthy populations occured in some years after the immigration of a VE patient. These data confirm the hypothesis that VE is transmitted from a VE patient to healthy persons. Among these persons fall ill those who have a hereditary determined increased sensitivity to VE which results in intrapopulation and intragenus accumulation of VE cases.
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pubmed_620_4596
|
pubmed_68_1030
|
Newly developed synthetic and recombinant thrombin inhibitors possess strong anticoagulant effects. Despite these effects, interactions of these agents with enzymes in the fibrinolytic network result in the modulation of such proteases as t-PA, u-PA and streptokinase. The inhibitory spectrum of several thrombin inhibitors [D-Phe-Pro-Arg-H(GYKI 14166), D-MePhe-Pro-Arg-H(GYKI 14766), Boc-D-Phe-Pro-Arg-H (GYKI 14451), Ac-D-Phe-Pro-boroArg-OH (DuP 714), recombinant hirudin (r-Hir) and unfractionated porcine mucosal heparin complexed with antithrombin III (Heparin/AT-III)] was studied towards various serine proteases such as tissue plasminogen activator (t-PA), plasmin, plasminogen/streptokinase complex, urokinase and kallikrein. Aprotinin was also studied in the same systems as the thrombin inhibitors. All four tripeptide derivatives were found to inhibit t-PA, plasmin and plasminogen/streptokinase complex at micromolar concentrations (IC50: 0.57 mM-3.3 microM). Boc-D-Phe-Pro-Arg-H and Ac-D-Phe-Pro-boroArg-OH also inhibited urokinase, while Ac-D-Phe-Pro-boroArg-OH inhibited kallikrein as well (IC50: 0.15 mM-16 microM). In contrast, r-Hir and Heparin/AT-III did not inhibit any of these enzymes at millimolar concentrations (IC50 > or = 1 mM). Aprotinin inhibited plasmin, plasminogen/streptokinase complex and kallikrein at micromolar concentrations (IC50: 3.1-0.85 microM). In a rabbit thrombolysis model, where pre-formed clots are lysed by streptokinase, simultaneous administration of D-MePhe-Pro-Arg-H or Ac-D-Phe-Pro-boroArg-OH, at concentrations approximately 1 mumol/kg, i.v. resulted in complete inhibition of the fibrinolytic process. Aprotinin at 0.1 mumol/kg, i.v. produced similar inhibition. These results demonstrate that thrombin inhibitors may exert significant antiprotease actions against various fibrinolytic enzymes.
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10.1016/0049-3848(94)90108-2
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pubmed_505_21037
|
Most evidence supports the view that ER alpha is responsible for estrogen (ovarian estradiol, E(2))-induced proliferation in the epithelial cells of the mammary gland, but despite this, proliferating epithelial cells do not express ER alpha. We have examined this apparent paradox by studying the role of ER alpha and ER beta in E(2)-induced proliferation in mammary glands (measured by BrdUrd incorporation into DNA) in mice with intact ER beta (WT mice) and those in which the ER beta gene has been inactivated (ER beta(-/-) mice). On treatment of ER beta(-/-) mice with E(2) or ovariectomized WT mice with E(2), tamoxifen, or a specific ER beta agonist (BAG), the number of BrdUrd-labeled cells in mammary glands increased from 3.4% in controls to 28-38% in the treated mice. This indicates that both ER alpha and ER beta can mediate E(2)-induced proliferation independently of each other. With specific antibodies, ER beta was found in both epithelial and stromal cells, whereas ER alpha was strictly epithelial. Within 4 h of a single dose of E(2), ER alpha was lost from the nuclei of epithelial cells. In WT mice, ER alpha reappeared by 24 h, but in ER beta(-/-) mice, return to the nucleus was delayed by 24 h. At 4 h after E(2), neither ER alpha nor progesterone receptor was detectable in BrdUrd-labeled nuclei but by 48 h after E(2), 29% of the BrdUrd-labeled cells expressed ER alpha, and 21-38% expressed progesterone receptor. During 3 weeks of continuous E(2) treatment, ER beta remained in the nucleus, but there was no detectable ER alpha. With tamoxifen treatment, ER alpha remained in the nucleus, but ER beta was lost. From these results, we conclude that ER alpha receives the proliferation signal from E(2), initiates DNA synthesis, and is then lost from cells. The subsequent steps in proliferation can proceed in the absence of either ER alpha or ER beta. ER beta facilitates the return of ER alpha to the nucleus and restores responsiveness to E(2). By down-regulating ER beta, tamoxifen may prolong refractoriness to E(2) in mammary epithelium.
|
10.1073/pnas.0307864100
|
pubmed_602_15122
|
PURPOSE
To determine reproducibility of volume measurements of small pulmonary nodules on computed tomographic (CT) scans and to estimate critical time to follow-up CT.
MATERIALS AND METHODS
One hundred fifteen pulmonary nodules for which two thin-section small-field-of-view CT scans were obtained and which were stable during 2-year observation were evaluated. A standard group of 94 nodules (with no or minimal artifact) and an expanded group of 105 nodules (including those with moderate artifacts) were examined. Percentage volume change (PVC) and monthly volumetric growth index (MVGI) were computed for each nodule pair. By using estimates of the variation in PVC in stable nodules as a function of initial diameter, critical time to follow-up CT was estimated; this time is the earliest point at which growth in a nodule of a given size can be reliably identified with repeat CT.
RESULTS
The SD of PVC decreased with increasing nodule size from 18.5% in 2-5-mm nodules to 10.6% in 5-8-mm nodules and to 7.47% in 8-10-mm nodules. Inclusion of cases with moderate motion artifacts increased the SD of PVC to 27.4% in 2-5-mm nodules, to 17.1% in 5-8-mm nodules, and to 19.3% in 8-10-mm nodules. Critical time to follow-up CT for nodules detected at baseline screening was 12, 5, and 3 months and 1 month for those with initial sizes of 2, 5, 8, and 10 mm, respectively. For nodules detected at annual repeat screening, it was 4 and 3 months and 1 month for nodules that were 3, 4, and 5 mm or larger in size, respectively. Mean MVGI in 94 standard cases was 0.06%, and standard error was 0.21%.
CONCLUSION
Factors that affect reproducibility of nodule volume measurements and critical time to follow-up CT include nodule size at detection, type of scan (baseline or annual repeat) on which the nodule is detected, and presence of patient-induced artifacts.
|
10.1148/radiol.2312030553
|
pubmed_414_1803
|
BACKGROUND
Dysregulated Notch signalling is believed to play an important role in the development and maintenance of T cell leukaemia. At a cellular level, Notch signalling promotes proliferation and inhibits apoptosis of T cell acute lymphoblastic leukaemia (T-ALL) cells. In this study we aimed to identify novel transcriptional targets of Notch signalling in the T-ALL cell line, Jurkat.
RESULTS
RNA was prepared from Jurkat cells retrovirally transduced with an empty vector (GFP-alone) or vectors containing constitutively active forms of Notch (N1DeltaE or N3DeltaE), and used for Affymetrix microarray analysis. A subset of genes found to be regulated by Notch was chosen for real-time PCR validation and in some cases, validation at the protein level, using several Notch-transduced T-ALL and non-T-ALL leukaemic cell lines. As expected, several known transcriptional target of Notch, such as HES1 and Deltex, were found to be overexpressed in Notch-transduced cells, however, many novel transcriptional targets of Notch signalling were identified using this approach. These included the T cell costimulatory molecule CD28, the anti-apoptotic protein GIMAP5, and inhibitor of DNA binding 1 (1D1).
CONCLUSION
The identification of such downstream Notch target genes provides insights into the mechanisms of Notch function in T cell leukaemia, and may help identify novel therapeutic targets in this disease.
|
10.1186/1476-4598-8-35
|
pubmed_277_21895
|
PURPOSE
This study investigated the effect of muscle stretching during warm-up on the risk of exercise-related injury.
METHODS
1538 male army recruits were randomly allocated to stretch or control groups. During the ensuing 12 wk of training, both groups performed active warm-up exercises before physical training sessions. In addition, the stretch group performed one 20-s static stretch under supervision for each of six major leg muscle groups during every warm-up. The control group did not stretch.
RESULTS
333 lower-limb injuries were recorded during the training period, including 214 soft-tissue injuries. There were 158 injuries in the stretch group and 175 in the control group. There was no significant effect of preexercise stretching on all-injuries risk (hazard ratio [HR] = 0.95, 95% CI 0.77-1.18), soft-tissue injury risk (HR = 0.83, 95% CI 0.63-1.09), or bone injury risk (HR = 1.22, 95% CI 0.86-1.76). Fitness (20-m progressive shuttle run test score), age, and enlistment date all significantly predicted injury risk (P < 0.01 for each), but height, weight, and body mass index did not.
CONCLUSION
A typical muscle stretching protocol performed during preexercise warm-ups does not produce clinically meaningful reductions in risk of exercise-related injury in army recruits. Fitness may be an important, modifiable risk factor.
|
10.1097/00005768-200002000-00004
|
pubmed_1072_14998
|
The benefit of oral bisphosphonates in reducing fracture risk in glucocorticoid-induced osteoporosis is controversial. We aimed to estimate the effectiveness of oral bisphosphonates in reducing fracture risk in a cohort of new chronic oral glucocorticoid users. We created three matched cohorts using health care administrative data from Ontario, Canada. We included residents aged 66 years and older initiating chronic oral glucocorticoids (≥450 mg prednisone equivalent and ≥2 glucocorticoid prescriptions within a 6-month window) between January 1998 and September 2014. Exposed patients were those who initiated an oral bisphosphonate (alendronate, etidronate, or risedronate) within the first 6 months of starting chronic oral glucocorticoid therapy. Exposed cohorts (3945 alendronate, 5825 risedronate, and 8464 etidronate) were each matched 1:1 to unexposed patients on glucocorticoid exposure, fracture risk factors, and propensity score. We examined incident hip (primary outcome), vertebral, forearm, and humerus fractures using Cox proportional hazard models. Alendronate (hazard ratio [HR] = 0.46, 95% confidence interval [CI] 0.25-0.80) and risedronate (HR = 0.58, 95% CI 0.36-0.90) were associated with reduced hip fracture risk. Alendronate (HR = 0.52, 95% CI 0.39-0.68), etidronate (HR = 0.59, 95% CI 0.48-0.73) and risedronate (HR = 0.47 95% CI 0.36-0.60) were associated with reduced vertebral fracture risk. No risk reduction in forearm or humerus fractures was apparent for any bisphosphonate. Among older chronic glucocorticoid initiators, all oral bisphosphonates reduced vertebral fracture risk, yet only alendronate and risedronate reduced hip fracture risk. Results were similar between men and women. We provided compelling evidence that early initiation of oral bisphosphonates during chronic oral glucocorticoid therapy is beneficial to prevent osteoporotic fractures. © 2017 American Society for Bone and Mineral Research.
|
10.1002/jbmr.3318
|
pubmed_1042_5153
|
The endothelial glycocalyx layer (EGL), which consists of long proteoglycans protruding from the endothelium, acts as a regulator of inflammation by preventing leukocyte engagement with adhesion molecules on the endothelial surface. The amount of resistance to adhesive events the EGL provides is the result of two properties: EGL thickness and stiffness. To determine these, we used an atomic force microscope to indent the surfaces of cultured endothelial cells with a glass bead and evaluated two different approaches for interpreting the resulting force-indentation curves. In one, we treat the EGL as a molecular brush, and in the other, we treat it as a thin elastic layer on an elastic half-space. The latter approach proved more robust in our hands and yielded a thickness of 110 nm and a modulus of 0.025 kPa. Neither value showed significant dependence on indentation rate. The brush model indicated a larger layer thickness (∼350 nm) but tended to result in larger uncertainties in the fitted parameters. The modulus of the endothelial cell was determined to be 3.0-6.5 kPa (1.5-2.5 kPa for the brush model), with a significant increase in modulus with increasing indentation rates. For forces and leukocyte properties in the physiological range, a model of a leukocyte interacting with the endothelium predicts that the number of molecules within bonding range should decrease by an order of magnitude because of the presence of a 110-nm-thick layer and even further for a glycocalyx with larger thickness. Consistent with these predictions, neutrophil adhesion increased for endothelial cells with reduced EGL thickness because they were grown in the absence of fluid shear stress. These studies establish a framework for understanding how glycocalyx layers with different thickness and stiffness limit adhesive events under homeostatic conditions and how glycocalyx damage or removal will increase leukocyte adhesion potential during inflammation.
|
10.1016/j.bpj.2020.02.010
|
pubmed_939_23444
|
Conductive polymers are attracting much attention for realizing active plasmonics on conventional static plasmonic nanostructures because of their variable dielectric functions. Combining organic conductive polymers with inorganic plasmonic nanostructures allows for the creation of active devices, such as active metasurfaces, reconfigurable metalenses and dynamic plasmonic holography. However, the complexity of such a combination, together with the poor control in polymer thickness and morphology, has limited the advancement of active plasmonics. Herein we report on the electrochemical coating of conductive polymers on pre-grown metal nanocrystals. Robust control of the polymer thickness and morphology is accomplished through the variation of the applied electrochemical potential. Various types of conductive polymers are coated on different metal nanocrystals, including Au, Pd and Pt. Active plasmonic color switching and H2O2 sensing are demonstrated with polyaniline-coated Au nanorods.
|
10.1039/d0nr05715k
|
pubmed_763_15850
|
BACKGROUND
Cutaneous T-cell lymphoma (CTCL) encompasses a broad range of lymphoproliferative diseases affecting the skin and can be clinically misleading due to its variable presentation. Nail alterations commonly appear in advanced-stage mycosis fungoides and true Sézary syndrome; however, they may be present in any stage of the disease. Although proper recognition of nail involvement in CTCL has both clinical and therapeutic value, specific nail findings have been infrequently described in the current literature.
OBSERVATIONS
We describe 4 patients with CTCL who presented with clinically significant nail alterations. The most common findings were nail discoloration, thickening, crumbling, onycholysis, and onychomadesis. Other notable findings included splinter hemorrhages, subungual hyperkeratosis, and anonychia.
CONCLUSIONS AND MESSAGE
The described cases illustrate many of the documented nail findings associated with CTCL and emphasize the variable nature of nail manifestations. The presence of specific nail alterations should increase the clinical suspicion of CTCL - especially in patients with concomitant systemic and/or cutaneous manifestations - and early biopsy specimens should be taken for diagnosis. Nail alterations should also be accurately described and monitored in all patients with biopsy-confirmed CTCL to help identify treatment response and detect disease recurrence.
|
10.1159/000433474
|
pubmed_764_11414
|
In this study we have developed a modified CLARK and DIAMOND (1992, 1993) method using the polymerase chain reaction to amplify amoebic ribosomal RNA genes that allow either specific detection of Entamoeba histolytica s. str. or amoeba species identification. DNA was isolated from cultured protozoa or from stool samples (cysts and/or trophozoites). Cultures of xenic or axenic material (also stool samples) were treated with Easy Genomic DNA Prep or Genomic DNA Prep Plus (A&A Biotechnology, Poland) for DNA isolation. With these new procedures, DNA can be obtained effectively and with high degree of purity. 13 amoeba strains were investigated. Three strains produced an 876 bp fragment with Psp5 and Psp3 primers (specific product for E. histolytica s. str). Three strains gave a specific 876 bp product for E. dispar with NPsp5 and NPsp3 primers. Two strains were E. moshkovskii as identified by KpnI digestion of PCR products obtained with RD5 and RD3 primers. Four strains (one of them was cultured in two laboratories) were E. invadens as identified by Hinfl or HhaI digestion of PCR products obtained with RD5 and RD3 primers. Characteristic RFLP patterns with these enzymes was also obtained for E. terrapinae and Blastocystis hominis. This RFLP analysis show significant promise as a medical diagnostic tool particularly useful for species identification.
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pubmed_764_11414
|
pubmed_1135_3441
|
Posterior reversible encephalopathy syndrome (PRES) is characterised clinically by encephalopathy, headache, visual disturbance and/or focal neurological symptoms. Bilateral cerebral oedema on T2 MRI sequences within the posterior cerebral white matter is the radiological hallmark, although involvement of the frontal lobe, basal ganglia and brainstem can occur. PRES with spinal cord involvement has been rarely reported and is under-recognised due to lack of myelopathic features in nearly half of the reported cases. We report a patient with PRES with spinal cord involvement and review the literature.
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pubmed_1135_3441
|
pubmed_730_11282
|
OBJECTIVE
To determine the weekly cervical shortening rates of the endocervical canal between 15 and 24 weeks' gestation in women at risk for pregnancy loss or spontaneous preterm birth.
METHODS
We performed a retrospective cohort study of transvaginal sonographic measurements of the endocervical canal length done at least twice between 15 and 24 weeks' gestation in women at risk for pregnancy loss and spontaneous preterm birth. The ultrasound diagnosis of cervical incompetence was defined as progressive shortening of the endocervical canal length to 2 cm or less either spontaneously or after application of transfundal pressure. Multivariable linear regression models were developed to determine the weekly crude rate of endocervical canal length shortening rates in cases of competent cervices and incompetent cervices, with incompetent cervices further stratified as those diagnosed at 15-19 weeks' and 20-24 weeks' gestation. Comparisons of the models for weekly rate of endocervical canal length shortening were performed.
RESULTS
The endocervical canal lengths were measured in 61 women (180 measurements) who did not develop ultrasound evidence of cervical incompetence and 28 women (103 measurements) who had ultrasound evidence of cervical incompetence. Between 15 and 24 weeks' gestation, competent cervices had a nonsignificant rate of endocervical canal length shortening (-0.03 cm/week). During this period in gestation, incompetent cervices had significantly greater endocervical canal length shortening (-0.41 cm/week, P < .001). The rate of endocervical canal length shortening of incompetent cervices diagnosed between 15 and 19 weeks' gestation was -0.52 cm/week (P < .001). The rate of endocervical canal length shortening in incompetent cervices diagnosed between 20 and 24 weeks' gestation was significant and varied from -0.49 cm/week to -0.80 cm/week at 20 and 24 weeks' gestation, respectively (P < .001). The models describing the rate of cervical shortening in the two groups of incompetent cervices were significantly different (P < .001). The sonographic detection of endocervical canal length shortening in the 28 cases of cervical incompetence was identified at a median (range) gestational age of 20 (16-24) weeks.
CONCLUSION
Weekly rates of endocervical canal length shortening were established, which may be useful for detecting and managing cervical incompetence in high-risk women examined with cervical sonography.
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10.1016/s0029-7844(98)00120-3
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