index
stringlengths 10
17
| text
stringlengths 101
18k
| doi
stringlengths 2
72
|
|---|---|---|
pubmed_140_17128
|
Background Inflammation and fibrosis play an important role in the pathogenesis of atrial fibrillation (AF) after myocardial infarction (MI). CTRP9 (C1q/tumor necrosis factor-related protein-9) as a secreted glycoprotein can reverse left ventricle remodeling post-MI, but its effects on MI-induced atrial inflammation, fibrosis, and associated AF are unknown. Methods and Results MI model rats received adenoviral supplementation of CTRP9 (Ad-CTRP9) by jugular-vein injection. Cardiac function, inflammatory, and fibrotic indexes and related signaling pathways, electrophysiological properties, and AF inducibility of atria in vivo and ex vivo were detected in 3 or 7 days after MI. shCTRP9 (short hairpin CTRP9) and shRNA were injected into rat and performed similar detection at day 5 or 10. Adverse atrial inflammation and fibrosis, cardiac dysfunction were induced in both MI and Ad-GFP (adenovirus-encoding green fluorescent protein)+MI rats. Systemic CTRP9 treatment improved cardiac dysfunction post-MI. CTRP9 markedly ameliorated macrophage infiltration and attenuated the inflammatory responses by downregulating interleukin-1β and interleukin-6, and upregulating interleukin-10, in 3 days post-MI; depressed left atrial fibrosis by decreasing the expressions of collagen types I and III, α-SMA, and transforming growth factor β1 in 7 days post-MI possibly through depressing the Toll-like receptor 4/nuclear factor-κB and Smad2/3 signaling pathways. Electrophysiologic recordings showed that increased AF inducibility and duration, and prolongation of interatrial conduction time induced by MI were attenuated by CTRP9; moreover, CTRP9 was negatively correlated with interleukin-1β and AF duration. Downregulation of CTRP9 aggravated atrial inflammation, fibrosis, susceptibility of AF and prolonged interatrial conduction time, without affecting cardiac function. Conclusions CTRP9 is effective at attenuating atrial inflammation and fibrosis, possibly via its inhibitory effects on the Toll-like receptor 4/nuclear factor-κB and Smad2/3 signaling pathways, and may be an original upstream therapy for AF in early phase of MI.
|
10.1161/JAHA.119.013133
|
pubmed_49_20341
|
It has been shown that the intake of carbohydrate (CHO)-containing beverages under resting conditions may lead to a rebound hypoglycemia and decreased performance when exercise is performed thereafter. The aim of the present investigation was to study the effect of CHO beverage consumption with different CHO sources and different concentrations, during warming-up under practice-like circumstances, on the regulation of blood glucose during exercise. Eighteen highly trained cyclists consumed a standardized breakfast at 8:00 AM and performed a warming-up procedure at 10:00 AM for 20 min. Warming-up was followed by a 7-min break after which the subjects cycled for 45 min at a heart rate of 150. During warming-up a CHO-containing beverage (either sucrose, fructose, maltodextrin, or glucose) or a placebo was consumed in random order. The test was performed twice, with 300 ml and 600 ml intake, to study a possible dose-response effect. The results of the study showed that warming-up and final exercise lead to an increase of the catecholamines and a decrease of insulin. During the 7-min break this response was reversed. Glucose and maltodextrin induced the same insulin response. Increasing volume and higher CHO concentrations induced a longer increase in blood glucose level compared with the placebo intake. The results showed that intake of CHO-containing beverages during warming-up followed by a small break does not lead to rebound hypoglycemia, independent of the amount of CHO ingested, but instead increases blood glucose.
|
10.1055/s-2007-1024956
|
pubmed_800_5667
|
The effects of microgravity on Jurkat cells--a T-lymphoid cell line--was studied on a sounding rocket flight. An automated pre-programmed instrument permitted the injection of fluorescent labelled concanavalin A (Con A), culture medium and/or fixative at given times. An in-flight 1 g centrifuge allowed the comparison of the data obtained in microgravity with a 1 g control having the same history related to launch and re-entry. After flight, the cells fixed either at the onset of microgravity or after a or 12 minute incubation time with fluorescent concanavalin A were labelled for vimentin and actin and analysed by fluorescence microscopy. Binding of Con A to Jurkat cells is not influenced by microgravity, whereas patching of the Con A receptors is significantly lower. A significant higher number of cells show changes in the structure of vimentin in microgravity. Most evident is the appearance of large bundles, significantly increased in the microgravity samples. No changes are found in the structure of actin and in the colocalisation of actin on the inner side of the cell membrane with the Con A receptors after binding of the mitogen.
|
10.1016/s0273-1177(99)00078-2
|
pubmed_669_13943
|
Hybrid semiconductor-metal nanocrystals manifest efficient photocatalytic activity related to the metal domain promoting charge carrier separation and providing an active catalytic site. The surface properties of such nanoparticles are also of paramount importance in determining their photocatalytic activity. Addressing the combination of surface effects in catalysis on metals, with the electronic properties of hybrid nanoparticles, we examined the effect of coating CdS-Au hybrid nanoparticles with sulfide, an anion that is expected to bind strongly to both domains, on the photocatalytic functionality. Upon sulfide coating, one-electron processes - namely the oxidative production of hydroxyl radicals and the reductive production of superoxide - were increased, whereas the activity for two-electron reduction processes - H2 and hydrogen peroxide generation - was hampered. These findings indicate a double-edged sword effect for sulfide coating that on one side relieves the hole extraction bottleneck from the semiconductor segment and, on the other hand, poisons the metal domain restricting its reductive capacity for the two-electron processes requiring a chemisorption step on the metal surface. The work further demonstrates the importance of surface properties for the photocatalytic action of such hybrid nanoparticle systems.
|
10.1021/acsami.1c17304
|
pubmed_636_12219
|
BACKGROUND AND PURPOSE
Clinical and experimental evidence suggests that spreading depolarization facilitates neuronal injury when its duration exceeds a certain time point, termed commitment point. We here investigated whether this commitment point is shifted to an earlier period, when spreading depolarization is accompanied by a perfusion deficit.
METHODS
Electrophysiological and cerebral blood flow changes were studied in a rat cranial window model followed by histological and immunohistochemical analyses of cortical damage.
RESULTS
In group 1, brain topical application of artificial cerebrospinal fluid (ACSF) with high K(+) concentration ([K(+)](ACSF)) for 1 hour allowed us to induce a depolarizing event of fixed duration with cerebral blood flow fluctuations around the baseline (short-lasting initial hypoperfusions followed by hyperemia). In group 2, coapplication of the NO-scavenger hemoglobin ([Hb](ACSF)) with high [K(+)](ACSF) caused a depolarizing event of similar duration, to which a severe perfusion deficit was coupled (=spreading ischemia). In group 3, intravenous coadministration of the L-type calcium channel antagonist nimodipine with brain topical application of high [K(+)](ACSF)/[Hb](ACSF) caused spreading ischemia to revert to spreading hyperemia. Whereas scattered neuronal injury occurred in the superficial cortical layers in the window areas of groups 1 and 3, necrosis of all layers with partial loss of the tissue texture and microglial activation were observed in group 2.
CONCLUSIONS
The results suggest that electrochemical failure of the cortex is more deleterious when it is accompanied by low perfusion. Thus, the commitment point of the cortex is not a universal value but depends on additional factors, such as the level of perfusion.
|
10.1161/STROKEAHA.112.660589
|
pubmed_294_18110
|
The paraoxonase polymorphism was analysed in the serum of 248 individuals from Saudi Arabia. The phenotyping method used was one based on the ratio of paraoxonase/arylesterase, described in earlier studies. The distribution of this ratio in the sample was trimodal and it provided a good resolution for the identification of three phenotypes: A-homozygotes with low activity; B-homozygotes with high activity; AB-the corresponding heterozygotes, with intermediate activity. Gene frequencies were 0.7296 for the allele A with low activity and 0.2704 for the allele B with high activity. These frequencies are close to those observed in Caucasian samples from North America and Europe. Phenotypic frequencies in the sample fit the Hardy-Weinberg equilibrium.
|
10.1097/00008571-199306000-00004
|
pubmed_378_1523
|
This study determined the effect of destruction of rostral ventrolateral medulla (RVLM)-C1 cells on integrated sympathetic and hormonal responses to hypotension or glucoprivation. Injection of anti-dopamine beta-hydroxylase-saporin into the RVLM resulted in 29-99% depletion of RVLM-C1 neurons and approximately 60% reduction in the number of A5 neurons. As in our previous study in unanesthetized rats, resting mean arterial pressure (MAP) was reduced by approximately 10 mmHg in rats with >80% depletion of RVLM-C1 cells compared with control rats, although resting heart rate (HR) did not differ significantly. In the present study, resting plasma levels of norepinephrine (NE) did not differ significantly between control rats and rats with >80% depletion of RVLM-C1 cells, although there was a tendency for RVLM-C1 lesioned rats to have lower levels. Also consistent with our previous study, hydralazine (HDZ)-evoked hypotension resulted in smaller increases in HR and plasma levels of NE in rats with >80% depletion of RVLM-C1 cells compared with control rats. Furthermore, the elevated plasma levels of posterior pituitary hormones vasopressin and oxytocin evoked by HDZ were blunted in RVLM-C1 lesioned rats compared with control rats, even though MAP fell to lower levels in the lesioned rats. Plasma renin activity, plasma osmolality, and plasma protein concentrations did not differ between control rats and rats with >80% depletion of RVLM-C1 neurons. In response to systemic administration of 2-deoxyglucose, the circulating level of epinephrine and the resulting hyperglycemia were attenuated in rats with >80% depletion of RVLM-C1 cells compared with control rats. These results demonstrate that RVLM-C1 cells, in addition to playing a role in acute cardiovascular reflexes, play an important role in integrated sympathetic and hormonal responses to homeostatic challenges such as hypotension and glucoprivation.
|
10.1152/ajpregu.00800.2005
|
pubmed_804_24083
|
BACKGROUND
Life expectancy (LE) refers to the number of years that an individual is expected to survive. Emphasis is frequently placed on the relationship between LE and the conditions under which a population lives, but fewer studies have investigated the relationship between stress factors associated with specific professions and their effects on LE. The aim of this study is to evaluate Brazilian neurosurgeons' life expectancies (BNLEs) and compare them with those of physicians (both Brazilian and foreign) from other fields, as well as with Brazilian nondoctors.
METHODS
The Brazilian Society of Neurosurgery death registry was used to obtain data that compared LEs from non-neurosurgeon physicians, as described in the national and international literature. BNLEs were also compared with the LEs of Brazilian citizens.
RESULTS
Fifty-one neurosurgeons died between 2009 and 2016. All were males. The mean age at death was 68.31 ± 17.71 years. Among all-cause mortality, the breakdown was 20% cardiovascular diseases, 39% malignancies, 10% external factors, 6% gastrointestinal disorders, 12% neurologic illnesses, and 14% unknown causes. BNLE was shorter than LE of male Brazilian citizens.
CONCLUSIONS
LE was similar among neurosurgeons and other doctors but shorter compared with Brazilian citizens. Further research is needed to provide data that can add to and confirm these results.
|
10.1016/j.wneu.2018.03.100
|
pubmed_722_10489
|
The significance of mastocytaemia in cats is different from that in dogs because it appears exclusively associated with mast cell neoplasia. The prevalence of mastocytaemia was 0.05% of all feline submissions to a private laboratory and 43% in cats with mast cell neoplasia. None of 30 healthy cats had mastocytaemia. There was no sex bias or significant age difference between mastocytaemic and non-mastocytaemic cats with mast cell tumours (MCT). Buffy coat (BC) examination was the best screening method for detection of mastocytaemia but direct blood film examination was more accurate for quantifying degree of mastocytaemia. BC examination should be performed in all cases of suspected/known mast cell neoplasia as mastocytaemia was missed on nearly 30% of occasions when direct film examination only was used. Mastocytaemia was associated with decreased haematocrit (HCT) but not with other haematological parameters. Mastocytaemic cats can survive significant lengths of time (up to 27 months) even when splenectomy is not performed.
|
10.1016/j.jfms.2010.08.003
|
pubmed_572_15201
|
Chiral cyclic amines can be prepared via intramolecular reductive amination of N-Boc-protected amino ketones in a one-pot process. With the complex of iridium and f-spiroPhos as the catalyst, a range of N-Boc-protected amino ketones are smoothly transformed into chiral cyclic free amines in high yields and excellent enantioselectivities (up to 97% ee). Moreover, this method can also be successfully applied to the synthesis of a κ-opioid receptor selective antagonist, (S)-1.
|
10.1021/acs.orglett.7b01828
|
pubmed_757_5680
|
AIMS
To examine mortality risk and causes of death in a cohort of a population of patients treated for gambling disorders in northern Italy from 1992 to 2019.
METHODS
Cohort study.
RESULTS
Half of the patients were diagnosed with psychiatric disorders, substance use disorder or alcohol dependence. The excess mortality compared to the general population (SMR) was 1.16 (0.85-1.58), more elevated among females aged 40 to 59 and males aged 20 to 29. Females had higher SMRs for all cancers and suicide; males for malignant neoplasm of liver, of lung, of prostate, and of bladder.
CONCLUSIONS
Despite patients increasing, subjects who most turn to the services are the most serious ones, in older age, with comorbid mental disorders and with a compromised health status. This is reflected in the high risk of death for all cancers.
|
10.4415/ANN_21_03_03
|
pubmed_432_11269
|
Frequency and character of the distribution of acrocentric chromosome associations are determined in 40 phenotypically healthy native inhabitants of the Latvian SSR (20 males and 20 females). The ability to associations is the lowest for chromosomes 15 and 22 and the highest for chromosomes 21, 14 and 13. It is found that a tendency to associations between chromosomes 21-21 (P less than 0.05) and 13-21 (P less than 0.01) is not of an accidental character.
|
pubmed_432_11269
|
pubmed_142_8229
|
We report that S100 proteins were reduced in patients with chronic rhinosinusitis (CRS). S100A8/9, which is important in epithelial barrier function, was particularly decreased in elderly patients with CRS. Epithelial expression of S100A8/9 is partly regulated by the IL-6 trans-signaling pathway. The goal of this study was to investigate whether or not age-related reduction of S100A8/9 in CRS is associated with blunting of IL-6 trans-signaling. The levels of IL-6, soluble IL-6 receptor (sIL-6R), soluble gp130 (sgp130), and S100A8/9 from control subjects (n = 10), and patients with CRS without nasal polyps (n = 13) and those with CRS with nasal polyps (CRSwNP) (n = 14), were measured by ELISA. Age-related differences in the level of each protein were investigated. Normal human bronchial epithelial cells were cultured in air-liquid interface and stimulated with IL-6/sIL-6R and tumor necrosis factor (TNF)-α with or without the addition of sgp130, a natural inhibitor of IL-6 trans-signaling. There was a significant age-related decline in S100A8/9 and an increase in sgp130 in nasal tissue samples from patients with CRSwNP, although there was no age-related difference in IL-6/sIL-6R production. Additionally, expression of the S100A8/9 gene and protein was increased significantly by IL-6/sIL-6R plus TNF-α in normal human bronchial epithelial cells. This increase was blocked by sgp130. These results suggest that increased sgp130 in older patients may inhibit IL-6 trans-signaling, impair barrier function, and decrease S1008/9 production in elderly patients with CRSwNP. Restoration of barrier function by targeting sgp130 may be a novel treatment strategy.
|
10.1165/rcmb.2015-0207RC
|
pubmed_714_21742
|
This report extends a control systems or cybernetic model of behavior to the behavior of groups of many individuals--organizations and institutions--operating together with technology as complex sociotechnical (ST) systems. The premise is that the level of quality in performance of a complex ST system is predicated upon the degree to which its organizational design incorporates elements of a closed-loop behavioral control system: control goals and objectives, sensory receptors, sensory feedback, learning and memory, effectors, and sensory feedback control. From a control systems perspective, ergonomics is essential to effective organizational self-regulation. If working conditions are poorly designed, work performance and safety and quality outcomes cannot be closely controlled. Conversely, as shown by field evidence, good design promotes synergism between ergonomics, safety, and quality as a closed-loop consequence of effective employee and organizational self-control of system performance, safety, and quality.
|
10.1080/10803548.1999.11076420
|
pubmed_1073_25624
|
We use grand canonical Monte Carlo simulation paired with multiple histogram reweighting, hyperparallel tempering and finite size scaling to investigate the structure and phase behaviour of monolayers of diblock copolymers. The chain molecules are arranged on the square lattice and we consider both fully flexible and rod-coil polymer models. In contrast to the majority of previous studies we assume that the interactions between the segments belonging to one of the two subunits are weaker than the remaining segment-segment interactions. We find that when the diblock copolymer is fully flexible, this choice of the interactions leads to a suppression of the ordered phase, and the phase behaviour is analogous to that of the fully flexible homopolymer model. However, when one of the subunits is rigid, we observe the formation of a novel hairpin chessboard ordered structure with fully stretched chains bent in the middle. The topology of the phase diagram depends on the chain length. For shorter chains the global phase diagram features a critical point and a triple point. For longer chains the gas-disordered liquid phase transition is suppressed and only the order-disorder transition remains stable. The resulting phase diagram is of the swan neck type.
|
10.1088/0953-8984/27/41/415101
|
pubmed_874_2115
|
Segmented copolymer networks (SCN) based on poly(2-ethyl-2-oxazoline) and containing 2-hydroxyethyl methacrylate, 2-hydroxypropyl acrylate, and/or methyl methacrylate segments have been evaluated as potential sustained release systems of the water soluble cardioselective β-blocker metoprolol tartrate. The structure and properties of the drug carriers were investigated by differential scanning calorimetry, attenuated total reflectance Fourier transform infrared spectroscopy, scanning electron microscopy, and atomic force microscopy. Swelling kinetics of SCNs in various media was followed, and the conditions for effective MT loading were specified. MT-loaded SCNs with drug content up to 80 wt.% were produced. The release kinetics of metoprolol tartrate from the systems was studied and it was shown that the conetworks of different structure and composition are able to sustain the metoprolol tartrate release without additional excipients.
|
10.1208/s12249-014-0120-0
|
pubmed_528_16232
|
Variants of herpes simplex virus type 2 (HSV-2) generated by virus passage in GMK-AH1 cells in the presence of the sulfated oligosaccharide PI-88 were analyzed. Many of these variants were substantially resistant to PI-88 in their initial infection of cells and/or their cell-to-cell spread. The major alteration detected in all variants resistant to PI-88 in the initial infection of cells was a frameshift mutation(s) in the glycoprotein G (gG) gene that resulted in the lack of protein expression. Molecular transfer of the altered gG gene into the wild-type background confirmed that the gG-deficient recombinants were resistant to PI-88. In addition to PI-88, all gG-deficient variants of HSV-2 were resistant to the sulfated polysaccharide heparin. The gG-deficient virions were capable of attaching to cells, and this activity was relatively resistant to PI-88. In addition to having a drug-resistant phenotype, the gG-deficient variants were inefficiently released from infected cells. Purified gG bound to heparin and showed the cell-binding activity which was inhibited by PI-88. Many PI-88 variants produced syncytia in cultured cells and contained alterations in gB, including the syncytium-inducing L792P amino acid substitution. Although this phenotype can enhance the lateral spread of HSV in cells, it conferred no virus resistance to PI-88. Some PI-88 variants also contained occasional alterations in gC, gD, gE, gK, and UL24. In conclusion, we found that glycoprotein gG, a mucin-like component of the HSV-2 envelope, was targeted by sulfated oligo- and polysaccharides. This is a novel finding that suggests the involvement of HSV-2 gG in interactions with sulfated polysaccharides, including cell surface glycosaminoglycans.
|
10.1128/JVI.01528-07
|
pubmed_845_6925
|
Borderline personality disorder (BPD) is one of the most common personality disorders seen in the general population. Among multiple identified risk factors, one of the most influential elements is exposure to an adverse childhood experience in terms of emotional, physical, or sexual abuse. A cascade of neuromorphological and epigenetic changes occurs in response to these childhood stressors, which may have a strong link to the development of BPD. PubMed and Google Scholar were searched for articles relevant to child abuse and the development of BPD. The search was not restricted to any time frame or geographic location. Significant epigenetic and neuromorphological changes are seen with child abuse, contributing to the development of BPD. Chronic stressors lead to hypothalamic-pituitary axis (HPA) activation, releasing cortisol that acts on the prefrontal cortex, amygdala, and hippocampus, producing the behavioral patterns seen in BPD. Overstimulation of gray matter leads to permanent neuromorphological changes, which can be visualized in functional MRI/brain scans. Hypermethylation of messenger ribonucleic acid in various sites suggests the impact of child abuse on the genetic level. Interestingly, the prevalence of BPD is seen equally in both genders but is diagnosed more frequently in females because they tend to be more likely to seek help. Understanding the impact of early age life stressors into adulthood calls for serious focus on early diagnosis and intervention. This implies the need for more studies in patients with BPD with or without any childhood traumatic experience and a better understanding of the changes that occur biopsychologically and genetically in response to trauma.
|
10.7759/cureus.9474
|
pubmed_568_5125
|
We demonstrate an integrated microneedle (MN)-smartphone nucleic acid amplification platform for "sample-to-answer" diagnosis of multiplexed plant pathogens within 30 min. This portable system consists of a polymeric MN patch for rapid nucleic acid extraction within a minute and a 3D-printed smartphone imaging device for loop-mediated isothermal amplification (LAMP) reaction and detection. We expanded the extraction of the MN technology for DNA targets as in the previous study (ACS Nano, 2019, 13, 6540-6549) to more fragile RNA biomarkers, evaluated the storability of the extracted nucleic acid samples on MN surfaces, and developed a smartphone-based LAMP amplification and fluorescent reader device that can quantify four LAMP reactions on the same chip. In addition, we have found that the MN patch containing as few as a single needle tip successfully extracted enough RNA for RT-PCR or RT-LAMP analysis. Moreover, MN-extracted RNA samples remained stable on MN surfaces for up to three days. The MN-smartphone platform has been used to detect both Phytophthora infestans DNA and tomato spotted wilt virus (TSWV) RNA down to 1 pg, comparable to the results from a benchtop thermal cycler. Finally, multiplexed detection of P. infestans and TSWV through a single extraction from infected tomato leaves and amplification on the smartphone without benchtop equipment was demonstrated.
|
10.1016/j.bios.2021.113312
|
pubmed_919_18946
|
Norfloxacin (NFX), a fluoroquinolone, was encapsulated in multilamellar liposomes (MLV) of soy-bean phosphatidylcholine at pH 7.0. The observed affinity of this class of drugs for hydrophobic environments, such as phospholipid bilayers, could lead to a better understanding of the mechanism of uptake in bacteria. The fluorescent properties of NFX were examined both free in solution and in MLV, using anisotropy and fluorescence quenching measurements. The latter data was treated with a chemometric method to deconvolute the overlapped spectra of zwitterionic and neutral species of NFX in equilibrium at this pH. The results show that NFX incorporates into the lipidic bilayers with two different distributions of species: the zwitterionic form in the lipid/aqueous interface, and the neutral one, more towards the center of the bilayer.
|
10.1366/0003702054615179
|
pubmed_429_3759
|
In dogs with gastric fistulae and Heidenhain pouches (HP) growth hormone release-inhibiting hormone (GH-RIH) infused intravenously in a dose of 2.5 mug per kg per hr inhibited almost completely acid and pepsin responses to pentagastrin, Urecholine, and a peptone. Histamine-induced acid secretion was more resistant to the inhibition by GH-RIH, and only acid secretion evoked by the lower doses of histamine was suppressed by this peptide. The inhibition of pentagastrin-induced gastric secretion was associated with a marked reduction in mucosal blood flow. The ratio of aminopyrine concentration in the gastric juice and blood plasma was not significantly changed by GH-RIH, indicating that the reduction in mucosal blood flow was secondary to an inhibition of gastric secretion. Gastric acid and serum gastrin responses to a peptone meal adjusted to pH 5.0 and kept in the main stomach at this same pH by intragastric titration were significantly decreased by GH-RIH, indicating that the observed acid inhibition could be attributed at least in part to the suppression of gastrin release. GH-RIH inhibited acid secretion from HP stimulated by liver extract in HP. The finding that GH-RIH inhibits gastric secretion induced by exogenous stimulants as well as by the direct chemical stimulation of the HP mucosa without changing serum gastrin level suggests that the major action of GH-RIH is a direct suppression of the oxyntic glands.
|
pubmed_429_3759
|
pubmed_123_1992
|
In the present investigation we have tested the hypothesis that spinal glutamate release by inflammatory stimuli causes hyperalgesia through sensitization of the primary sensory neurons associated with nociception. In these experiments, the rat paw hyperalgesia pressure test in which inflammatory hyperalgesia is blocked by the intraplantar administration of morphine (MPH) or SNAP, a NO donor was used. Glutamate and glutamatergic ionotropic agonists such as NMDA or AMPA injected intrathecally (i.t.) caused a dose-dependent hyperalgesia. Quisqualate or ACPD, both of which are glutamate metabotropic receptor agonists, had no hyperalgesic effect. The hyperalgesic response to glutamate and NMDA injected i.t. was antagonized by the intraplantar (i.pl.) injection of either MPH or SNAP. This observation indicates that the hyperalgesia induced by glutamate acting through an NMDA pre-synaptic receptor causes sensitization of the primary sensory neurons. Confirming that the analgesia by i.pl. injection of SNAP or MPH was due to an action in primary peripheral sensory neurons, it was shown that pretreatment of the paws with methylene blue (MB, an inhibitor of guanylate cyclase) or with MB and L-NMMA (an inhibitor of NO synthase) abolished their respective analgesic effect. AMPA i.t. induced hyperalgesia was not inhibited by either i.pl. administration of MPH or SNAP, indicating that its hyperalgesic capacity results from an action at a site other than the primary sensory neuron.(ABSTRACT TRUNCATED AT 250 WORDS)
|
10.1016/0028-3908(94)90052-3
|
pubmed_1059_413
|
Distribution of the alkaline phosphatase and 5'-nucleotidase activity was studied in blood serum by means of gel filtration through Sephadex G-200 with jaundices of different origin. Both enzymes have two forms differing in the molecular weight, 5'-nucleotidase presenting mainly a high-molecular form in contrast to alkaline phosphatase. This form activity for both enzymes is higher with obturative jaundices as compared to liver cirrhosis and virus hepatitis. The results of incubating sera with desoxicholate and the subsequent gel filtration in its presence, as well as polyacrylamide gel electrophoresis of butanol extracts of the fractions containing high-molecular fragments, evidence for the fact that these fragments are lipoproteid complexes.
|
pubmed_1059_413
|
pubmed_60_9225
|
Despite the rising incidence of clear cell renal cell carcinoma, the molecular events that support its development and progression remain unclear. Herein, we evaluate the association of endothelin 2 expression with both clear cell renal cell carcinoma development and progression-free survival. We conducted real-time polymerase chain reaction to determine endothelin 2 expression levels on 238 patients who underwent nephrectomy for localized clear cell renal cell carcinoma, 161 of whom also had adjacent normal kidney samples available for analysis. To evaluate associations with clear cell renal cell carcinoma development, linear mixed models were used to compare differential expression between tumor and a normal kidney as well as to explore interactions with clinicopathologic features. To evaluate associations with prognosis, Cox proportional hazards models were used to assess the association of progression-free survival and endothelin 2 expression in tumor tissue. Overall, endothelin 2 expression was higher in tumor samples versus patient-matched normal kidney samples, with an average fold change of 1.99 (95% confidence interval, 1.48-2.60; P < .0001). This overexpression in tumor versus normal kidney samples was more pronounced in low- compared with high-grade tumors (interaction, P = .0002), in early- compared with late-stage tumors (interaction, P = .001), and in tumors without compared with those with necrosis (interaction, P = .001). Moreover, an increasing endothelin 2 expression in tumors was associated with a longer progression-free survival (hazard ratio, 0.89; 95% confidence interval, 0.80-0.99; P = .03); however, after controlling for known clinicopathologic factors, this association was attenuated (hazard ratio, 0.99; 95% confidence interval, 0.89-1.09; P = .7). Up-regulation of endothelin 2 is a common and early event in localized clear cell renal cell carcinoma. Higher tumor expression of endothelin 2 is associated with a longer progression-free survival but not after adjustment for well-known pathologic indices. Thus, although endothelin 2 does not appear to be an independent prognostic marker, there is evidence of a putative role in clear cell renal cell carcinoma progression. If supportive mechanistic data can be produced, endothelin 2 could represent a potential target for chemopreventive or neoadjuvant therapeutics for clear cell renal cell carcinoma.
|
10.1016/j.humpath.2011.07.011
|
pubmed_82_6534
|
Myogenesis is determined by a set of myogenic differentiation factors that are, in turn, regulated by a number of peptide growth factors. During embryonic mouse tongue formation, transforming growth factor alpha (TGF alpha), epidermal growth factor (EGF), and their cognate receptor (EGFR) are co-expressed spatially and temporally with desmin, a muscle-specific structural protein. This investigation tested the hypothesis that TGF alpha directly regulates the myogenic program in developing tongue myoblasts. Mandibular processes from the first branchial arch of embryonic day 10.5 (E10.5) mouse embryos were microdissected and explanted into an organ culture system using serumless chemically defined medium. Exogenous TGF alpha at 10 and 20 ng/ml specifically increased the amount of desmin expression and the number of desmin-positive cells without affecting the general growth and development of the mandibles. This inductive response was detected as early as 2 days after treatment and sustained up to 9 days in culture. EGFR antisense oligonucleotides (30 microM) as well as tyrphostin (80 microM) were able to negate TGF alpha-induced up-regulation of desmin expression. These data indicate that autocrine and/or paracrine action of TGF alpha promotes tongue myogenesis, and that this action is mediated through functional kinase activity of the EGFR. We speculate that the myogenic program in the developing mouse tongue is dependent upon growth factor mediated cell-cell communication of mesenchymal cells originating from the occipital somites and ectomesenchymal cells originating from the cranial neural crest.
|
10.1002/(SICI)1097-0177(199809)213:1<71::AID-AJA7>3.0.CO;2-V
|
pubmed_103_13403
|
National calls to improve student academic success in college have sparked the development of bridge programs designed to help students transition from high school to college. We designed a 2-week Summer Bridge program that taught introductory biology content in an active-learning way. Through a set of exploratory interviews, we unexpectedly identified that Bridge students had developed sophisticated views of active learning, even though this was not an explicit goal of the program. We conducted an additional set of semistructured interviews that focused on active learning and compared the interviews of Bridge students with those from non-Bridge students who had been eligible for but did not participate in the program. We used the constant comparative method to identify themes from the interviews. We found that Bridge students perceived that, because they knew how to approach active learning and viewed it as important, they benefited more from active learning in introductory biology than non-Bridge students. Specifically, Bridge students seemed to be more aware of their own learning gains from participating in active learning. Compared with the majority of non-Bridge students, the majority of Bridge students described using a greater variety of strategies to maximize their experiences in active learning. Finally, in contrast to non-Bridge students, Bridge students indicated that they take an equitable approach to group work. These findings suggest that we may be able to prime students to maximize their own and other's experiences in active learning.
|
10.1187/cbe.16-05-0161
|
pubmed_969_11646
|
The colony-stimulating factors (CSF) belong to a group of proteins which regulate blood cell production. Human monocytes allowed to adhere express high levels of M-CSF transcripts and secreted protein at 24 h in the presence but not in the absence of indomethacin (Indo), an inhibitor of prostaglandin E (PGE) production. When induced with lipopolysaccharide (LPS), adherent monocytes express M-CSF, G-CSF, and GM-CSF transcripts and secrete these proteins and TNF. M-CSF and GM-CSF messages increase in LPS-induced monocytes by the addition of Indo, while G-CSF mRNA appears to decrease. Exogenous addition of PGE-2 to LPS-induced monocytes down-modulates the expression of M-CSF and GM-CSF transcripts. G-CSF message is elevated, suggesting an alternate pathway to G-CSF regulation. PGE-2 inhibits the secretion of CSFs and TNF. In contrast, LPS-induced monocytes held 24 h in nonadherent culture express G- and GM-CSF but not M-CSF. Monocytes that are adhered for 24 h and then treated with LPS for an additional 24 h express only M-CSF message and secrete M-CSF and TNF. PGE-2 added with LPS during the 24-48 h induction blocks M-CSF and TNF production, but appears to enhance M-CSF message expression, in contrast to its effect on 0 h inductions. These results suggest that adherence alone induces M-CSF gene expression, but low levels of PGE or other arachidonic acid metabolites limit this expression. Other events in 1 d-cultured monocytes block the ability to induce G-CSF and GM-CSF expression with LPS, and block the suppressive effect of PGE-2 on M-CSF expression at the RNA level.
|
10.1002/jlb.47.3.275
|
pubmed_1018_10031
|
Incubation temperature and the amount of water taken up by eggs from the substrate during incubation affects hatchling size and morphology in many oviparous reptiles. The Brisbane river turtle Emydura signata lays hard-shelled eggs and hatchling mass was unaffected by the amount of water gained or lost during incubation. Constant temperature incubation of eggs at 24 degrees C, 26 degrees C, 28 degrees C and 31 degrees C had no effect on hatchling mass, yolk-free hatchling mass, residual yolk mass, carapace length, carapace width, plastron length or plastron width. However, hatchlings incubated at 26 degrees C and 28 degrees C had wider heads than hatchlings incubated at 24 degrees C and 31 degrees C. Incubation period varied inversely with incubation temperature, while the rate of increase in oxygen consumption during the first part of incubation and the peak rate of oxygen consumption varied directly with incubation temperature. The total amount of oxygen consumed during development and hatchling production cost was significantly greater at 24 degrees C than at 26 degrees C, 28 degrees C and 31 degrees C. Hatchling mass and dimensions and total embryonic energy expenditure was directly proportional to initial egg mass.
|
10.1007/s003600050159
|
pubmed_844_13416
|
Acid-loaded Trypanosoma cruzi amastigotes and trypomastigotes regained normal cytoplasmic pH (pHi), as measured in cells loaded with 2',7'-bis-(2-carboxyethyl)-5(6)-carboxyfluorescein (BCECF), by a process that was sensitive to bafilomycin A1 at concentrations comparable to those that inhibited vacuolar (V) H+-ATPases from different sources. Steady-state pHi was also decreased by similar concentrations of bafilomycin A1 in a concentration-dependent manner. The efflux of H+ equivalents from amastigotes and trypomastigotes was measured by following changes in the fluorescence of extracellular BCECF. Basal H+ extrusion in the presence of glucose was 15.4+/-2.8 (S.D.) nmol of H+/min per 10(8) amastigotes and 6. 37+/-0.8 nmol of H+/min per 10(8) trypomastigotes. Bafilomycin A1 treatment significantly decreased the efflux of H+ equivalents by amastigotes (8.9+/-2.2 nmol of H+/min per 10(8) cells), but not by trypomastigotes (5.1+/-1.7 nmol of H+/min per 10(8) cells). The localization of the V-H+-ATPase of T. cruzi was investigated by immunocytochemistry. Confocal and electron microscopy indicated that, in addition to being located in cytoplasmic vacuoles, the V-H+-ATPase of different stages of T. cruzi is also located in the plasma membrane. However, no labelling was detected in the plasma membrane lining the flagellar pocket of the different developmental stages. Surface localization of the V-H+-ATPase was confirmed by experiments involving the biotinylation of cell surface proteins and immunoprecipitation with antibodies against the V-H+-ATPase. Taken together, the results are consistent with the presence of a functional V-H+-ATPase in the plasma membrane of amastigotes and with an important role for intracellular acidic compartments in the maintenance of pHi in different stages of T. cruzi.
|
10.1042/bj3320695
|
pubmed_443_7874
|
PURPOSE
Our objectives were to compare the prevalence of oropharyngeal mucosal lesions among human immunodeficiency virus (HIV) seropositive and demographically similar seronegative women, and to determine the association of oral lesions with immunosuppression, substance abuse, use of medications, and utilization of dental services.
POPULATION AND METHODS
Participants in a multicenter, longitudinal cohort study of HIV infection in women were evaluated at baseline by interview, physical examination, and laboratory studies.
RESULTS
Oropharyngeal pathology was found in 40% of seropositive and 23% of seronegative women. Oral candidiasis was identified in 15% of seropositive and 3% of seronegative women. Among seropositive women, history of previous oral candidiasis, lower CD4 lymphocyte counts, and current antibiotic use were associated with oral candidiasis. Hairy leukoplakia was identified in 5% of seropositive women and was significantly associated with lower CD4 lymphocyte counts. Gingival erythema and ulcerative gingivitis were found in 23% of participants overall, but were unrelated to HIV serostatus or CD4 lymphocyte count. Substance abuse, lack of dental care, and African-American race were associated with gingival pathology.
CONCLUSION
The high prevalence of oral lesions among HIV seropositive and at-risk seronegative women underscores the need for routine oral examination and targeted treatment of this population.
|
10.1016/s0002-9343(98)00110-7
|
pubmed_1136_14118
|
Leishmaniasis is endemic in the Middle East, and both cutaneous and visceral forms are reported from the region ranging from the Levant to Afghanistan. The potential and proven phlebotomine sand fly vectors and reservoir hosts of the Leishmaniases species in Afghanistan, Iran, Iraq, Israel, Jordan, Lebanon, Saudi Arabia, Syria, Turkey, and Yemen are described. This region has seen a movement of populations across the area, due to both military and civilian strife. Refugees, armed forces, and multi-national contractors are particularly at risk to acquire this disease. There has been an upsurge in Leishmaniasis research, especially as new foci are exposed and the need to protect the naïve populations moving into endemic areas becomes a public health priority. New sand fly vectors and animal reservoirs have been discovered while novel control methods are being evaluated. Modern molecular techniques are now being used more routinely and revealing some unusual findings. The aim of this review is to collate the most recent data on the burden of the disease, diagnostic applications, eco-epidemiology of vectors, and reservoir hosts, and how the control projects have been developing in the Middle East.
|
10.1089/vbz.2010.0068
|
pubmed_261_14558
|
BACKGROUND
Alterations in intestinal microflora have been linked to the development of allergic disease. Recent studies suggest that healthy infant immune development may depend on the establishment of a diverse gut microbiota rather than the presence or absence of specific microbial strains.
OBJECTIVES
We investigated the relationship between diversity of gut microbiota in the early postnatal period and subsequent development of eczema and atopy in the first year of life.
METHODS
Fecal samples were collected 1 wk after birth from 98 infants at high risk of allergic disease, who were followed prospectively to age 12 months. Fecal microbial diversity was assessed by terminal restriction fragment length polymorphism (T-RFLP) using restriction enzymes Sau96I and AluI, with a greater number of peaks representing greater diversity of bacterial communities.
RESULTS
Microbial diversity at day 7 was significantly lower in infants with eczema at age 12 months as compared to infants without eczema (AluI mean number of peaks 13.1 vs. 15.5, p = 0.003, 95% CI for difference in means -3.9, -0.8; Sau96I 14.7 vs. 17.2, p = 0.03, 95% CI -4.9, -0.3). No differences were observed for atopic compared to non-atopic infants, or infants with two allergic parents compared to those with one or no allergic parent.
CONCLUSIONS
A more diverse intestinal microbiota in the first week of life is associated with a reduced risk of subsequent eczema in infants at increased risk of allergic disease. Interventions that enhance microbial diversity in early life may provide an effective means for the prevention of eczema in high-risk infants.
|
10.1111/j.1399-3038.2012.01328.x
|
pubmed_990_6584
|
Heat shock alters the susceptibility of tumor cells to chemotherapeutic agents. We conducted experiments to study the regulation of expression of heat shock proteins (HSP) in 17 beta-estradiol-treated T47-D cells, a human breast cancer cell line. Cells exposed to 17 beta-estradiol for 24-48 h displayed increased expression of glucose regulated protein 78kD (GRP-78) and 94kD (GRP-94), as shown by [35S]methionine incorporation and Western blotting experiments. The increase was time (5 h to 48 h)-dependent at 1 nM and 1 microM 17 beta-estradiol. Cells overexpressing GRP-78 and -94 after treatment with 17 beta-estradiol displayed resistance against heat shock (47 degrees C for 50 min)-induced death. Removal of external Ca2+ or treatment of cells with BAPTA (a Ca2+ chelator) did not alter the synthesis of GRP-78 and -94, suggesting that the 17 beta-estradiol effect on the synthesis of GRP-78 and -94 is Ca(2+)-independent. In addition, exposure of cells to 17 beta-estradiol up to 100 microM did not increase [Ca2+]i, which further supports the view that the estrogen-induced GRPs are not regulated by [Ca2+]i. Treatment with H89 (a protein kinase A inhibitor, 1 microM, 30 min) or GF-109203X (a protein kinase C inhibitor, 1 microM, 30 min) also did not change the GRP synthesis, indicating that protein kinase A and C are not involved in regulation of GRP synthesis.
|
pubmed_990_6584
|
pubmed_471_25404
|
The development of a copper-catalyzed azide-alkyne cycloaddition (CuAAC) protocol for the decoration of coiled coils with N-cysteine peptide thioesters as cyclic peptide precursors is presented. The reaction conditions include tert-butanol/PBS as the solvent and CuSO4/THPTA/ascorbate as the catalytic system. During these studies, partial formylation of N-terminal cysteine peptides is observed. Mechanistic analysis leads to identification of the formyl source and, hence, to the development of reaction conditions, under which the undesired side reaction was suppressed.
|
10.1021/acs.orglett.8b03261
|
pubmed_710_18882
|
Objective: To determine equivalent threshold sound pressure levels (ETSPL) for the RadioEar IP30 insert earphone for standardised short-term stimuli: IEC 60645-3 reference clicks and tonebursts in the frequency range from 250 Hz to 6 kHz, using the standardised peak-equivalent ETSPL procedure (peETSPL) and a new proposal based on the unweighted equivalent continuous sound pressure level LZeq. of the periodically repeated short-term stimuli (LZeqETSPL).Design: Determination of peETSPL and LZeqETSPL hearing threshold levels with otologically normal test subjects under the conditions given in ISO 389-9 using the standardised occluded-ear simulator according to IEC 60318-4.Study sample: The study was based on tests with 25 subjects.Results: The peETSPLs for the RadioEar IP30 insert earphone were compared with the respective reference threshold levels of the insert earphone ER-3A as standardised in the ISO 389 standards series. The LZeqETSPL approach was tested by estimating the LZeqETSPLs from the peRETSPLs and comparing the estimate with the direct results.Conclusions: Equivalent hearing threshold levels for standardised short-term stimuli for the RadioEar IP30 insert earphone were determined according to ISO 389-9 and given as both peETPSL and LZeqETSPL. The RMS-based LZeqETSPL approach turned out to be well applicable for the RadioEar IP30 insert earphone.
|
10.1080/14992027.2019.1682690
|
pubmed_1048_23551
|
BACKGROUND
During the past few years nurses precepting undergraduate nursing students have been put under greater pressure because of increased number of students admitted to the universities combined with a shortage of clinical placements. One solution is the preceptor model peer learning where two students are tutored by the same preceptor simultaneously.
OBJECTIVES
The aim of this study was to describe the variation of registered nurses' conceptions of preceptorship in a peer learning model for undergraduate nursing students.
DESIGN
The study used a qualitative descriptive design and a phenomenographic approach.
SETTINGS
The interviews took place at somatic and psychiatric units at two different hospitals in southern Sweden.
PARTICIPANTS
Twelve informants participated who had worked as registered nurses between 1-17years and acted as peer learning preceptors between 2month and 6years.
METHODS
Each nurse was interviewed individually using a semi structured interview guide. Follow up questions were used to make the informants develop and deepen their answers.
RESULTS
Four different descriptive categories emerged in the study: 1) Preceptorship in peer learning generates development and new perspectives 2) Preceptorship in peer learning enables student reflection and independence 3) Preceptorship in peer learning engenders insufficiency and stress 4) Preceptorship in peer learning requires education and support.
CONCLUSIONS
The result of this study showed that preceptors conceived that peer learning enabled them to take a step back which gave them a new role and perspectives. The consequence was that the students could be more independent which saved time for some of the preceptors. However, some preceptors perceived insufficiency and stress while working with two students. It is also important to educate both students and preceptors to optimise the use of peer learning.
|
10.1016/j.nedt.2016.10.015
|
pubmed_159_4749
|
We present a new scheme for diabatizing electronic potential energy surfaces for use within the recently implemented direct-dynamics grid-based class of computational nuclear quantum dynamics methods, called Procrustes diabatization. Calculations on the well-studied molecular systems LiF and the butatriene cation, using both Procrustes diabatization and the previously implemented propagation and projection diabatization schemes, have allowed detailed comparisons to be made, which indicate that the new method combines the best features of the older approaches; it generates smooth surfaces, which cross at the correct molecular geometries, reproduces interstate couplings accurately, and hence allows the correct modeling of non-adiabatic dynamics.
|
10.1063/5.0003254
|
pubmed_1125_18768
|
Second-harmonic generation in 60GeS(2)-20Ga(2)S(3)-20KBr chalcohalide glass was investigated by the thermal poling method. A large second-order nonlinear susceptibility, as high as 7.0 pm/V, was obtained in a poled sample by Maker fringe analysis. We believe this to be the first time that a clear second-harmonic wave was observed in chalcohalide glasses containing large amount of alkali ions (6.25 at. %). Such observation is of great potential use in all optical waveguide devices.
|
10.1364/ol.31.003492
|
pubmed_63_19595
|
Determination of the levels of adenosine 5'-triphosphate (ATP), adenosine 5'-diphosphate (ADP), and adenosine 5'-monophosphate (AMP) in royal jelly is important for the study of its pharmacological activities, health benefits, and adenosine phosphate degradation. In this study was developed a novel method to determine ATP, ADP, and AMP levels in royal jelly using accelerated solvent extraction (ASE) followed by online cleanup and high-performance liquid chromatography (HPLC) with diode array detection (DAD). The optimum extraction conditions were obtained using an 11 mL ASE cell, ethanol/water (5:5 v/v) as the extraction solvent, 1500 psi, 80 degrees C, a 5 min static time, and a 60% flush volume. Optimum separation of the three compounds was achieved in <25 min using a Waters XBridge Shield RP18 column with 0.05 mol L(-1) NH(4)H(2)PO(4) (pH 5.70) and acetonitrile as the mobile phase. Detection was performed at 257 nm. The method was sensitive (LOD <or= 0.32 mg L(-1)), repeatable (RSD <or= 4.5%), accurate (recovery rates of 87.6-94.2% with RSD <or= 5.4), and precise (intraday RSD <or= 8.5%, interday RSD <or= 3.4%). The ASE extraction procedures developed here were compared with the classical adenosine phosphate extraction procedures (perchloric acid). The results indicate that the two techniques are similar in terms of recovery and reproducibility, but when other factors such as extraction time, environmental protection, and worker's health are considered, ASE is preferable to the classical extraction method. With this ASE-HPLC method, a minisurvey of ATP, ADP, and AMP levels in 15 samples of royal jelly of different origins was performed. Sample results indicated that the AMP concentration was 24.2-2214.4 mg kg(-1), whereas ATP and ADP were not detectable or present only at low levels.
|
10.1021/jf900853q
|
pubmed_910_16624
|
Experimental data suggest that egg intake could have a beneficial impact on several risk factors for type 2 diabetes. In contrast, some recent epidemiological studies have concluded that egg consumption may increase diabetes risk. We performed a dose-response meta-analysis of prospective cohorts on the relation of egg consumption with incident type 2 diabetes. We searched for cohort studies that assessed egg consumption and diabetes risk up to June 2015. We identified 416 articles and extracted data independently and in duplicate from ten eligible studies. We used random-effects generalised least squares models for pooled dose-response estimation based on thirteen estimates. Our study included 251 213 individuals and 12 156 incident type 2 diabetes cases. Egg intake was associated with incident type 2 diabetes (risk ratio (RR)/egg per d 1·13; 95 % CI 1·04, 1·22). We identified study location as a major source of heterogeneity. For studies conducted in the USA, we observed a stronger association (RR 1·47; 95 % CI 1·32, 1·64), whereas results were null for studies conducted elsewhere. Studies considered to be of high quality yielded null findings (RR 0·94; 95 % CI 0·74, 1·19). The association of egg intake with increased risk of incident type 2 diabetes may be restricted to US cohort studies. There are limited data to support a biological mechanism that could underlie this association; thus, the possibility that these results may be due to residual confounding by dietary behaviours restricted to certain populations cannot be excluded.
|
10.1017/S000711451600146X
|
pubmed_732_20323
|
Wilson's disease (WD) is a rare autosomal recessive genetic disorder of copper metabolism resulting in brain damage, liver failure, and neurological impairment and psychiatric disturbances, as a result of excessive copper accumulation in the brain, liver, kidneys and eyes. ATP7B, encoding a copper transporter P-ATPase was identified as the causative gene of WD. Mutations in the ATP7B gene lead to the defection of the transmembrane transporter so that it can not metabolize copper effectively. We reported the clinical and molecular features of three unrelated and non-consanguineous WD patients. We performed molecular genetic analysis of the ATP7B gene in all cases by DNA sequencing, and revealed 7 novel single nucleotide polymorphisms (SNPs) and 8 well known mutations. Among them, that novel SNP (c. -520 C>T) and two well known mutations (c. 2310 C>G/p. Leu700Leu, c. 2333 G>T/A/p. Arg778Leu/Gln) coexisted in all patients and they were heterozygous and homozygous in the youngest case, respectively, indicating that they may be correlated to the pathogenesis and potentially used as a genetic biomarker for early WD diagnosis.
|
pubmed_732_20323
|
pubmed_1058_3310
|
cis-Diamminedichloroplatinum(II) (cis-DDP or cisplatin) is a widely used anticancer drug that is most effective against tumors of the testis. Although cisplatin is believed to mediate its cytotoxicity through the formation of DNA adducts, the precise biochemical mechanisms underlying its antitumor activity and selectivity for testicular tumors remain elusive. Of significance are the high-mobility group (HMG) domain and other proteins that bind specifically to cisplatin-DNA adducts. The present study focuses on the testis-specific HMG domain protein human SRY (hSRY). The full-length hSRY protein and its HMG domain region alone were expressed in Escherichia coli and purified to homogeneity. The affinities and specificities of full-length hSRY and the hSRY-HMG domain for 20 bp DNAs containing a single cis-[Pt(NH3)2{d(GpG)-N7(1), -N7(2)}] intrastrand cross-link or a putative hSRY target site in the CD3epsilon gene enhancer (AACAAAG) were determined in electrophoretic mobility shift assays. Full-length hSRY bound to the major 1,2-d(GpG) cisplatin adduct with a Kd(app) of 120 +/- 10 nM and exhibited a 20-fold specificity over unmodified DNA. The HMG domain of hSRY was sufficient for this interaction. The hSRY-HMG domain recognized the 1,2-d(GpG) intrastrand cross-link with higher affinity [Kd(app) = 4 +/- 0.7 nM] but with lower specificity (5-fold) than the full-length protein. The affinities of full-length hSRY and the hSRY-HMG domain for a single cisplatin-DNA adduct were comparable to those for the putative target sequence AACAAAG. These data suggest that cisplatin-DNA adducts may compete with specific DNA sequences in vivo for the binding of human SRY. A possible role for this testis-specific protein in the cytotoxicity and organotropic specificity of cisplatin for testicular tumors is proposed.
|
10.1021/bi971675q
|
pubmed_910_23871
|
Practitioners and policy-makers need information about the relative frequency of dental anomalies among children in their region. This study investigated the prevalence of different oral anomalies among schoolchildren in Sana'a city, Yemen. A sample of 1000 private and public schoolchildren aged 4-12 years were examined by the same examiner using disposable tongue blades. The total prevalence of oral anomalies was 15.1%, most commonly in boys (male:female ratio 3.2:1) aged 7-12 years. The most prevalent dental anomaly related to hard tissues was tooth hypoplasia (2.8%), followed by hypocalcification (2.6%), then microdontia (0.5%), macrodontia (0.4%), hypodontia (0.4%), supernumerary teeth (0.3%), tooth transposition (0.3%), dental fusion (0.2%) and gemination (0.2%). The most prevalent soft tissues anomaly was fissured tongue (4.0%), followed by ankyloglossia (1.8%), geographic tongue (0.9%), macroglossia (0.4%) and hairy tongue (0.3%). Appropriate measures need to be taken early to mitigate the negative impact and later costs of treatment of anomalies.
|
pubmed_910_23871
|
pubmed_859_3294
|
Aging is accompanied by changes in physiology over time, which remains the largest risk of chronic diseases. The aim of this study was to explore the gender-specific bidirectional relations between the risk of chronic diseases and serum traits in a 3-year longitudinal study. A hierarchical non-linear model with random effects was used to assess the temporal patterns of anthropometric and serum traits from 2017 to 2019 among 2,338 participants. To assess the directional effect between the risk of chronic diseases and serum traits, a bivariate cross-lagged panel model (CLPM) was used to estimate the structural relations of repeatedly measured variables at three different time points. Candidate SNPs were analyzed and genotyped in MassARRAY Analyzer 4 platforms. In this study, metabolic syndrome (MS) score increased with aging in females, whereas the fatty liver disease (FLD) index decreased with aging in males; the MS score was negatively correlated with TB in females, and FLD index was positively related to urea in males; CLPM showed that the MS score predicted total bilirubin (TB) in females, and urea predicted the FLD index in males. Additionally, rs2292354 in G protein-coupled receptor kinase interactor 2 (GIT2) was associated with the MS score and TB in aged females. Our study suggests the potential gender-specific causal associations between development in MS and increase in TB level in females, and rise in urea level and improved FLD index in males. The SNP rs2292354 we investigated might be a biomarker for predicting MS in the elderly Chinese Han population.
|
10.3389/fpubh.2022.1003505
|
pubmed_1044_17224
|
Vitiligo is the utmost common depigmenting condition consequential from melanocyte loss from the basal layer of the epidermis. Vitiligo disease mostly affects dark-skinned races and made them more sensitive to UV radiation. It is also linked with some autoimmune diseases and various psychosocial difficulties. Melanocyte loss led to depigmentation in vitiligo, is a major concern over decades, and even affects an individual's day-to-day life severely. All the theories; including autoimmune, Autocytotoxic, and neural collectively decipher either prime impact on the melanogenesis inhibition or deficient adhesion inspired melanocytes disappearance. Previously it has been described that melanocyte loss in vitiligo patients is caused by defective adhesion. Melanocyte death by apoptosis is mainly occurred due to melanocyte detachment or migration from the basal layer and further followed by trans epidermal migration. Various cell surface molecules i.e., cell adhesion molecules (CAMs) in affiliation with neighbouring cells and extracellular matrix (ECM) encompass a typical cell adhesion process. All these ECM molecules along with transcription factors help in the survival and maintenance of pigmentary cells/melanocytes. Therefore, in this issue, we have tried to compile the literature available on melanocyte detachment/apoptosis in ECM due to the alteration in adhesion molecules and matrix metalloproteinases (MMPs) which are driven by known/unknown transcription factors.
|
10.2174/1566524022666220621125552
|
pubmed_875_17119
|
Chronic thromboembolic pulmonary hypertension is a morbid condition associated with complications such as hemoptysis, right heart failure, paradoxical embolism, and even death. There is no known association of chronic thromboembolic pulmonary hypertension with pulmonary arteriovenous malformation. Possible hypothesis for this association is an increased pulmonary vascular resistance leading to the compensatory formation of pulmonary arteriovenous malformation. We present one such case presenting with hemoptysis that was managed with endovascular treatment.
|
10.4103/0971-3026.184415
|
pubmed_702_4675
|
Molecular biology tools have enhanced the capability of the forensic scientist to characterize biological evidence to the point where it is feasible to analyze minute samples and achieve high levels of individualization. Even with the forensic DNA field's maturity, there still are a number of areas where improvements can be made. These include: enabling the typing of samples of limited quantity and quality; using genetic information and novel markers to provide investigative leads; enhancing automation with robotics, different chemistries, and better software tools; employing alternate platforms for typing DNA samples; developing integrated microfluidic/microfabrication devices to process DNA samples with higher throughput, faster turnaround times, lower risk of contamination, reduced labor, and less consumption of evidentiary samples; and exploiting high-throughput sequencing, particularly for attribution in microbial forensics cases. Knowledge gaps and new directions have been identified where molecular biology will likely guide the field of forensics. This review aims to provide a roadmap to guide those interested in contributing to the further development of forensic genetics.
|
10.2144/000113136
|
pubmed_314_21591
|
OBJECTIVE
The purpose of this study was to prospectively assess the performance of real-time tissue elastography (RTE) in the evaluation of breast masses and correlate RTE and American College of Radiology Breast Imaging Reporting and Data System (BI-RADS) assessments with pathologic findings.
METHODS
Informed consent was obtained from all patients for this Health Insurance Portability and Accountability Act-compliant, Institutional Review Board-approved study. Patients with sonographically visible breast lesions for which a biopsy was recommended were considered potential study participants. Between October 2006 and February 2008, 186 consecutive women with 200 lesions were enrolled. Twelve lesions in 11 patients were excluded, resulting in a study population of 188 lesions in 175 women. After routine B-mode sonographic examination, RTE was performed using a manual free-hand compression technique. Study lesions were assigned elasticity scores (ES) based on the system proposed by Itoh et al (Radiology 2006; 239:341-350), where 1 is normal and 5 represents abnormal strain. The lesion size on RTE and B-mode imaging was compared. Results were correlated with BI-RADS assessment and pathologic findings.
RESULTS
Pathologic examination revealed 61 of 188 malignancies (32.4%) and 127 of 188 benign lesions (67.6%). Of the malignant lesions, 84% had ES of 5 and 4, whereas 76% of benign lesions had ES of 1 and 2. The sensitivity of RTE was 92.7%, and specificity was 85.8%, with 4 false-negative and 16 false-positive results. Of the biopsy-proven benign BI-RADS 4A lesions, 63 of 76 (82.9%) had ES of 1 and 2, consistent with normal tissue.
CONCLUSIONS
Real-time tissue elastography may provide additional characterization of breast lesions, improving specificity, particularly for low-suspicion lesions.
|
10.7863/jum.2010.29.4.551
|
pubmed_583_22325
|
Healthy cells continually produce low levels of reactive oxygen species (ROS), which are buffered by multiple antioxidant systems. Imbalance between ROS production and elimination results in oxidative stress, which has been implicated in aging and in numerous human diseases, including cancer and diabetes. Selenoproteins are a family of proteins that contain the amino acid selenocysteine, encoded by an in-frame UGA. Those selenoproteins whose function is identified are catalytically active in redox processes, representing one of the main enzymatic antioxidant systems and important mediators of the beneficial role of selenium in human health. Nevertheless, the function of most selenoproteins remains unknown; this included Selenoprotein N (SelN), the only selenoprotein directly associated with a human genetic disease. Mutations of the SelN gene cause SEPN1-related myopathy, a particular early-onset muscle disorder. Recent studies have identified SelN as a key protein in cell protection against oxidative stress and redox-related calcium homeostasis. Furthermore, an effective ex vivo treatment of SelN deficiency has been identified, paving the way to a clinical therapy. In this review we discuss the physiological and pathophysiological role of SelN and the interest of SEPN1-related myopathy as a model paradigm to understand and target therapeutically other selenoproteins involved in human health and disease.
|
10.1089/ars.2009.2890
|
pubmed_41_6083
|
Phagocytosis of filamentous bacteria occurs through tubular phagocytic cups (tPCs) and takes many minutes to engulf these filaments into phagosomes. Contravening the canonical phagocytic pathway, tPCs mature by fusing with endosomes. Using this model, we observed the sequential recruitment of early and late endolysosomal markers to the elongating tPCs. Surprisingly, the regulatory early endosomal lipid phosphatidylinositol-3-phosphate (PtdIns(3)P) persists on tPCs as long as their luminal pH remains neutral. Interestingly, by manipulating cellular pH, we determined that PtdIns(3)P behaves similarly in canonical phagosomes as well as endosomes. We found that this is the product of a pH-based mechanism that induces the dissociation of the Vps34 class III phosphatidylinositol-3-kinase from these organelles as they acidify. The detachment of Vps34 stops the production of PtdIns(3)P, allowing for the turnover of this lipid by PIKfyve. Given that PtdIns(3)P-dependent signaling is important for multiple cellular pathways, this mechanism for pH-dependent regulation of Vps34 could be at the center of many PtdIns(3)P-dependent cellular processes.
|
10.1083/jcb.201702179
|
pubmed_751_14107
|
The arterial-coronary sinus lactate difference was measured in 17 patients after each step of a programmed ventricular stimulation protocol consisting of single, double, and triple extrastimuli, first at a basic drive cycle length of 600 msec, then at 400 msec, with an inter-train interval of 4 seconds. Four patients had no structural heart disease, four had an idiopathic dilated cardiomyopathy, and nine had coronary artery disease with a significant stenosis in at least one branch of the left coronary artery. Net myocardial lactate production during programmed ventricular stimulation was observed in three patients with coronary artery disease, but not in any patient without coronary artery disease. Among the patients who had coronary artery disease, net myocardial lactate production generally occurred in the patients who had more severe coronary artery disease. Exercise-induced ischemia, as demonstrated by a stress thallium-201 test, did not correlate with myocardial lactate production during programmed ventricular stimulation. Programmed ventricular stimulation, with a stimulation protocol typically used in many electrophysiology laboratories, is capable of inducing myocardial ischemia in at least some patients who have coronary artery disease. This finding suggests that myocardial ischemia may potentially influence the results of programmed ventricular stimulation in some patients with coronary artery disease.
|
10.1016/0002-8703(86)90136-5
|
pubmed_1013_7692
|
Morbidity and mortality of respiratory diseases are linked to airway obstruction by mucus but there are still no specific, safe, and effective drugs to correct this phenotype. The need for better treatment requires a new understanding of the basis for mucus production. In that regard, studies of human airway epithelial cells in primary culture show that a mucin granule constituent known as chloride channel accessory 1 (CLCA1) is required for inducible expression of the inflammatory mucin MUC5AC in response to potent type 2 cytokines. However, it remained uncertain whether CLCLA1 is necessary for mucus production in vivo. Conventional approaches to functional biology using targeted gene knockout were difficult due to the functional redundancy of additional Clca genes in mice not found in humans. We reasoned that CLCA1 function might be better addressed in pigs that maintain the same four-member CLCA gene locus and the corresponding mucosal and submucosal populations of mucous cells found in humans. Here we develop to our knowledge the first CLCA1-gene-deficient (CLCA1) pig and show that these animals exhibit loss of MUC5AC+ mucous cells throughout the airway mucosa of the lung without affecting comparable cells in the tracheal mucosa or MUC5B+ mucous cells in submucosal glands. Similarly, CLCA1 pigs exhibit loss of MUC5AC+ mucous cells in the intestinal mucosa without affecting MUC2+ mucous cells. These data establish CLCA1 function for controlling MUC5AC expression as a marker of mucus production and provide a new animal model to study mucus production at respiratory and intestinal sites.
|
10.1152/ajplung.00443.2021
|
pubmed_143_12099
|
GTP cyclohydrolase (GCYH-I) is an enzyme in the folate biosynthesis pathway that has not been previously exploited as an antibiotic target, although several pathogens including N. gonorrhoeae use a form of the enzyme GCYH-IB that is structurally distinct from the human homologue GCYH-IA. A comparison of the crystal structures of GCYH-IA and -IB with the nM inhibitor 8-oxo-GTP bound shows that the active site of GCYH-IB is larger and differently shaped. Based on this structural information, we designed and synthesized a small set of 8-oxo-G derivatives with ether linkages at O6 and O8 expected to displace water molecules from the expanded active site of GCYH-IB. The most potent of these compounds, G3, is selective for GCYH-IB, supporting the premise that potent and selective inhibitors of GCYH-IB could constitute a new class of small molecule antibiotics.
|
10.1016/j.bmcl.2019.126818
|
pubmed_428_7493
|
BACKGROUND
Hypertrophic scarring (HS) is a severe disease, and results from unusual wound healing. Col1A1 could promote the hypertrophic scar formation, and the expression of Col1A1 in HS tissue was markedly higher than that in the normal. In present study, we aimed to identify miRNAs as post-transcriptional regulators of Col1A1 in HS.
METHODS
MicroRNA-98 was selected as the key miRNA comprised in HS. The mRNA levels of miR-98 in HS tissues and the matched normal skin tissues were determined by qRT-PCR. MTT and flow cytometry were used to determine the influence of miR-98 on cell proliferation and apoptosis of HSFBs, respectively. Col1A1 was found to be the target gene of miR-98 using luciferase reporter assay. Luciferase assay was performed to determine the relative luciferase activity in mimic NC, miR-98 mimic, inhibitor NC and miR-98 inhibitor with Col1A13'-UTR wt or Col1A13'-UTR mt reporter plasmids. The protein expression of Col1A1 in HSFBs after transfection with mimic NC, miR-98 mimic, inhibitor NC and miR-98 inhibitor were determined by western blotting.
RESULTS
The mRNA level of miR-98 in HS tissues was much higher than that in the control. Transfection of HSFBs with a miR-98 mimic reduced the cell viability of HSFBs and increased the apoptosis portion of HSFBs, while inhibition of miR-98 increased cell viability and decreased apoptosis portion of HSFBs. miR-98 inhibitor increased the relative luciferase activity significantly when cotransfected with the Col1A1-UTR reporter plasmid, while the mutant reporter plasmid abolished the miR-98 inhibitor-mediated increase in luciferase activity. Western blotting revealed that overexpression of miR-98 decreased the expression of Col1A1.
CONCLUSIONS
Overexpression of miR-98 repressed the proliferation of HSFBs by targeting Col1A1.
|
10.1186/s40659-017-0127-6
|
pubmed_290_26127
|
Natural and human disturbance along with climate change pose major challenges for resource management. This is relevant in natural forests, where conflict can occur between water provision and industrial logging. As a result, conversion of old forests to young, fast-growing stands through logging can dramatically reduce streamflow and water yield. We modelled changes in stream run-off and hence water yield from a forest catchment in response to clearcut logging and compared this with projected climate change (using a Representative Climate Futures [RCFs] approach). We focused on the Thomson Catchment, which is the largest single catchment for the city of Melbourne, south-eastern Australia. Within this catchment, we targeted our analysis at montane ash-type eucalypt forests, as these receive the most rainfall and are subject to clearcutting. We used several forest management scenarios to model changes in water yield over time. For our analysis of projected climate change, we employed a range of RCFs that represent 'consensus', 'wettest' and 'driest' scenarios to model the impacts of multiple Representative Concentration Pathways (RCPs). Our initial spatial analysis revealed that 42% of the ash-type eucalypt forests in the Thomson Catchment have been logged. Under historical and continued logging, stream runoff decreases by 40,211 ML by 2090 compared with a hypothetical baseline if logging had ceased in 1995 and 34,059 ML if logging continues beyond 2019. These losses exceed the projected impacts of climate change under the consensus and wettest scenarios, but the driest scenarios are projected to exceed these losses, consisting of 49,998 ML and 69,474 ML for RCP 4.5 and RCP 8.5, respectively. We suggest logging be excluded from the Thomson Catchment because of decreasing stream flows due to climate change and an increasing water demand due to human population growth. This study provides a quantitative approach for highlighting how resource conflicts can be magnified under climate change.
|
10.1016/j.scitotenv.2019.06.298
|
pubmed_403_17977
|
We examined the effects of biochar and effective mircoorganisms (EM) application on growth and photosynthetic characteristics of Sesbania cannabina in the Yellow River Delta, by a pot experiment with different EM treatments (without EM addition, EM-; with EM addition, EM+) and a gradient of biochar treatments (0, B0; 0.5%, B1; 1.5%, B2; 3%, B3; biochar weight/soil weight). The growth parameters, photosynthetic light response curve and chlorophyll fluorescence characteristics of S. cannabina were measured. The results showed that the EM+B3 treatment had the best effect among all the treatments. Compared with the EM-B0 treatment, the EM+B3 treatment increased height, stem diameter, and total biomass by 69.5%, 90.0% and 141.1%, respectively. Biochar and EM significantly improved photosynthetic capacity. Compared with the EM-B0 treatment, the EM+B3 treatment significantly enhanced the maximum light response of net photosynthetic rate, transpiration rate, water use efficiency, and stomatal conductance by 93.8%, 35.1%, 43.4%, and 34.8%, respectively. Biochar and EM improved the parameters of chlorophyll fluorescence. Compared with the EM-B0 treatment, the EM+B3 treatment significantly increased the potential photochemical efficiency, the actual photochemical efficiency, the apparent electron transport rate and the non-photochemical quenching coefficient by 25.8%, 31.5%, 37.2%, and 56.8%, respectively. The parameters of growth, photosynthesis and chlorophyll fluorescence increased with the increasing biochar under EM+ treatments, whereas the B3 treatment had negative effect under EM- treatments. The co-addition of EM and 3% biochar (EM+B3) could improve the photosynthetic capacity and chlorophyll fluorescence characteristics of S. cannabina, broaden light ecological amplitude, boost the water retention and drought resistance property, and promote the growth of S. cannabina.
|
10.13287/j.1001-9332.202009.006
|
pubmed_849_6241
|
Montmorillonite nanoparticles have been physically incorporated within a crosslinked collagen/poly(N-isopropyl acrylamide) network in order to adjust the properties of the stimuli-responsive hybrid systems. The research underlines both the influence of hydrogel composition and nanoparticle type on hybrid hydrogel properties. The dispersion of the montmorillonite nanoparticles in polymeric matrix have been visualized by SEM, TEM and AFM techniques and quantitatively and qualitatively estimated using near infrared chemical imaging. The electrical charge of the nanoparticles influenced the polymeric chain arrangement and the pore size. The morphologies of the nanoparticulated layers are partially exfoliated or intercalated and uniformly dispersed through the polymeric semi-interpenetrated network based on collagen and poly(N-isopropyl acrylamide). The hybrid hydrogels exhibit pseudoplastic behavior and the addition of nanoparticles has resulted in the increase of the complex viscosity. The adhesion capacity was affected mainly by the presence of organically modified montmorillonites.
|
pubmed_849_6241
|
pubmed_190_8529
|
T-cell therapy after hematopoietic stem cell transplantation (HSCT) has been used alone or in combination with immunosuppression to cure hematologic malignancies and to prevent disease recurrence. Here, we describe the outcome of patients with high-risk/advanced stage hematologic malignancies, who received T-cell depleted (TCD) haploidentical-HSCT (haplo-HSCT) combined with donor T lymphocytes pretreated with IL-10 (ALT-TEN trial). IL-10-anergized donor T cells (IL-10-DLI) contained T regulatory type 1 (Tr1) cells specific for the host alloantigens, limiting donor-vs.-host-reactivity, and memory T cells able to respond to pathogens. IL-10-DLI were infused in 12 patients with the goal of improving immune reconstitution after haplo-HSCT without increasing the risk of graft-versus-host-disease (GvHD). IL-10-DLI led to fast immune reconstitution in five patients. In four out of the five patients, total T-cell counts, TCR-Vβ repertoire and T-cell functions progressively normalized after IL-10-DLI. These four patients are alive, in complete disease remission and immunosuppression-free at 7.2 years (median follow-up) after haplo-HSCT. Transient GvHD was observed in the immune reconstituted (IR) patients, despite persistent host-specific hypo-responsiveness of donor T cells in vitro and enrichment of cells with Tr1-specific biomarkers in vivo. Gene-expression profiles of IR patients showed a common signature of tolerance. This study provides the first indication of the feasibility of Tr1 cell-based therapy and paves way for the use of these Tr1 cells as adjuvant treatment for malignancies and immune-mediated disorders.
|
10.3389/fimmu.2014.00016
|
pubmed_886_12004
|
The insulin-like growth factor receptor I (IGF-IR) plays an essential role in transformation by promoting cell growth and protecting cancer cells from apoptosis. Aberrant IGF-IR signaling is implicated in several types of tumors, including carcinomas of the lung, breast, prostate, pancreas, liver, and colon. However, the contribution of the IGF-IR to the development of the transformed phenotype in urothelial cells has not been clearly established. In this study we demonstrated that the IGF-IR is overexpressed in invasive bladder cancer tissues compared with nonmalignant controls. We have investigated the role of the IGF-IR in bladder cancer by using urothelial carcinoma-derived 5637 and T24 cells. Although activation of the IGF-IR did not appreciably affect their growth, it did promote migration and stimulate in vitro wound closure and invasion. These effects required the activation of the Akt and Mitogen-activated protein kinase (MAPK) pathways as well as IGF-I-induced Akt- and MAPK-dependent phosphorylation of paxillin, which relocated at dynamic focal adhesions and was necessary for promoting motility in bladder cancer cells. Our results provide the first evidence for a role of the IGF-IR in motility and invasion of bladder cancer cells and support the hypothesis that the IGF-IR may play a critical role in the establishment of the invasive phenotype in urothelial neoplasia. Thus, the IGF-IR may also serve as a novel biomarker for bladder cancer.
|
10.2353/ajpath.2010.090904
|
pubmed_177_4880
|
Malignant melanoma of the uvea is the most common primary malignant tumor in the eye. We aimed to analyze GNAQ and GNA11 mutations in uveal melanomas using formalin-fixed, paraffin-embedded material and correlate the results with clinicopathological parameters. Tumor tissue was microdissected followed by amplification of GNAQ exon 4 and 5, GNA11 exon 4 and 5, and finally analyzed by Sanger sequencing. A total of 64.4 GNA11/GNAQ mutations, including ten yet unreported, were found. Two cases showed multiple mutations. Overall survival was significantly shorter in the uveal melanoma cohort with GNAQ exon 5 mutation. In concordance with previous studies, high frequencies of mutations in GNAQ or GNA11 were detected. Interestingly, in about 20% of UM, not yet reported mutations in GNAQ or GNA11 were seen. Rarely, uveal melanoma may harbor double mutations in GNAQ and/or GNA11. Recent data imply, that implementation of GNAQ/GNA11 mutation analysis in routine diagnostic procedures might be helpful for future therapeutic decisions.
|
10.1007/s12253-017-0371-7
|
pubmed_1025_1280
|
Oral emergency vaccination against classical swine fever is a powerful tool to control disease outbreaks among European wild boar and thus to safeguard domestic pigs in affected regions. In the past, when virus detection was mainly done using virus isolation in cell culture or antigen enzyme-linked immunosorbent assays, modified live vaccine strains like C-strain "Riems", were barely detectable after oral vaccination campaigns. Nowadays, the use of highly sensitive molecular techniques has given rise to an increase in vaccine virus detections. This was also the case during the 2009 outbreak among German wild boar and the subsequent vaccination campaigns. To guarantee a rapid differentiation of truly infected from C-strain vaccinated animals, a combination of differentiating multiplex rRT-PCR assays with partial sequencing was implemented. Here, we report on the rational and use of this approach and the lessons learned during execution. It was shown that positive results in the recently developed vaccine strain (genotype) specific rRT-PCR assay can be taken as almost evidentiary whereas negative results should be confirmed by partial sequencing. Thus, combination of multiplex rRT-PCR assays as a first line differentiation with partial sequencing can be recommended for a genetic DIVA strategy in areas with oral vaccination against classical swine fever in wild boars.
|
10.1016/j.vetmic.2011.05.039
|
pubmed_504_13890
|
Vascular plant pathogens travel long distances through host veins, leading to life-threatening, systemic infections. In contrast, nonvascular pathogens remain restricted to infection sites, triggering localized symptom development. The contrasting features of vascular and nonvascular diseases suggest distinct etiologies, but the basis for each remains unclear. Here, we show that the hydrolase CbsA acts as a phenotypic switch between vascular and nonvascular plant pathogenesis. cbsA was enriched in genomes of vascular phytopathogenic bacteria in the family Xanthomonadaceae and absent in most nonvascular species. CbsA expression allowed nonvascular Xanthomonas to cause vascular blight, while cbsA mutagenesis resulted in reduction of vascular or enhanced nonvascular symptom development. Phylogenetic hypothesis testing further revealed that cbsA was lost in multiple nonvascular lineages and more recently gained by some vascular subgroups, suggesting that vascular pathogenesis is ancestral. Our results overall demonstrate how the gain and loss of single loci can facilitate the evolution of complex ecological traits.
|
10.1126/sciadv.abc4516
|
pubmed_286_9544
|
The article describes the medical approach of a frequent pathology, chronic venous insufficiency. Chronic venous insufficiency requires early diagnosis as well as an evaluation of the associated risk factors; also, patients need to understand the disease and its treatment, and to become compliant with all their physician's recommendations. Importantly, the physician should correctly evaluate the disease and decide the best option for the patient. These days, it is crucial that the patient benefits from optimal treatment choice in order to prevent complications. CVI is a potentially severe pathology that has been underdiagnosed and undertreated for a long time and requires patience from the patient as well as care from the physician.
|
pubmed_286_9544
|
pubmed_349_5213
|
In recent years, sheep (Ovis aries) have emerged as a useful animal model for neurological research due to their relatively large brain and blood vessel size, their cortical architecture, and their docile temperament. However, the functional anatomy of sheep brain is not as well studied as that of non-human primates, rodents, and felines. For example, while the location of the sheep motor cortex has been known for many years, there have been few studies of the somatotopy of the motor cortex and there were a range of discrepancies across them. The motivation for this review is to provide a definitive resource for studies of the sheep motor cortex. This work critically reviews the literature examining the organization of the motor cortex in sheep, utilizing studies that have applied direct electrical stimulation and histological methods A clearer understanding of the sheep brain will facilitate and progress the use of this species as a scientific animal model for neurological research.
|
10.1016/j.neubiorev.2017.06.002
|
pubmed_910_16235
|
Quantification of proteins by mass spectrometry at the level of entire proteomes has become a central aspect in contemporary proteomics. Sequential Window Acquisition of all THeoretical fragment-ion spectra (SWATH) mass spectrometry is a label-free protein quantification method enabling parallel quantification of up to several thousand proteins, thereby granting a comprehensive overview of highly complex samples. We optimized several parameters of the mass spectrometrical detection to increase the size of the library, enhance the precision of protein quantifications and decrease systematic errors induced by fragment ion interference. By these means enhanced differential analyses facilitate the detection of more significantly regulated proteins with a dynamic range of over three orders of magnitude.
|
10.1016/j.jprot.2016.04.021
|
pubmed_801_7048
|
Statin therapy plays a central role in decreasing the morbidity and mortality associated with cardiovascular disease. However, prescribed statins are only effective if they are taken by patients on a regular basis, known as medication adherence. The factors that influence patient adherence to statin therapy can be categorized into patient factors, physician factors, and health system factors, often with interactions between the categories. Patient factors include demographics, socioeconomic status, comorbidities, and side effects. Physician factors include the physician's own adherence to applying guideline recommendations, office visits, and their interactions with patients. Health system factors include issues such as cost and access to care. Physicians should be aware of the various elements that may influence a patient's likelihood to take statin medications to improve adherence and provide the best possible patient outcomes.
|
10.1007/s11886-011-0221-2
|
pubmed_765_19997
|
The outbreak of Corona Virus Disease 2019 (COVID-19) in various countries at the end of last year has transferred traditional face-to-face teaching to online education platforms, which directly affects the quality of education. Taking user satisfaction on online education platforms in China as the research object, this paper uses a questionnaire survey and web crawler to collect experience data of online and offline users, constructs a customer satisfaction index system by analyzing emotion and the existing literature for quantitative analysis, and builds aback propagation (BP) neural network model to forecast user satisfaction. The conclusion shows that users' personal factors have no direct influence on user satisfaction, while platform availability has the greatest influence on user satisfaction. Finally, suggestions on improving the online education platform are given to escalate the level of online education during the COVID-19 pandemic, so as to promote the reform of information-based education.
|
10.3390/healthcare8030200
|
pubmed_20_14938
|
Reports and quantitative descriptions of wild primate births are rare due to the frequent occurrence of nighttime parturitions. The aim of this study was to describe in detail one daytime birth event in a free-ranging band of Sichuan snub-nosed monkeys (Rhinopithecus roxellana), a highly endangered colobine species endemic to China. Using focal-animal sampling, we recorded both the birth event and behavior of the mother and other group members. The partum stage lasted 4 min 10 s. Immediately after parturition, the mother severed the umbilical cord, ingested the placenta, and cleaned the newborn. During the birthing process, the mother received what may possibly be described as birth assistance from one multiparous female within the same one-male unit. Although "aunting" or infant caregiving behavior has previously been reported in coloblines, this is the first putative case of birth assistance in a nonhuman primate.
|
10.1007/s10329-015-0506-y
|
pubmed_537_1440
|
1. Equimolar amounts of gamma-L-glutamyl-L-3,4-dihydroxyphenylalanine (gludopa) and gamma-L-glutamyl-5-hydroxy-L-tryptophan were infused separately and together in eight healthy, salt-replete male subjects in a placebo-controlled, cross-over study to investigate whether the administration of one amine precursor affects the renal metabolism of the other and to determine whether dopamine or 5-hydroxytryptamine would be generated preferentially. The overall effect on sodium excretion was also measured when both precursors were administered simultaneously. 2. Administration of gludopa was associated with marked increases in the urinary excretion of L-dopa, dopamine and 3,4-dihydroxyphenylacetic acid, together with a rise in the urinary excretion of sodium. gamma-L-Glutamyl-5-hydroxy-L-tryptophan, on the other hand, produced marked increases in the urinary excretion of 5-hydroxy-L-tryptophan, 5-hydroxy-tryptamine and 5-hydroxyindoleacetic acid, and this was accompanied by a slight, but non-significant, reduction in sodium excretion. About 27% of the infused dose of gludopa (on a molar basis) was recovered in the urine as dopamine whereas 15% of the given dose of gamma-L-glutamyl-5-hydroxy-L-tryptophan was excreted as 5-hydroxytryptamine. 3. The urinary excretion values of L-dopa, dopamine and 3,4-dihydroxyphenylacetic acid after the simultaneous infusion of gludopa and gamma-L-glutamyl-5-hydroxy-L-tryptophan were not significantly different from those observed after infusion of gludopa only. Similarly, the urinary excretion values of 5-hydroxy-L-tryptophan, 5-hydroxytryptamine and 5-hydroxy-indoleacetic acid during the co-infusion were similar to those measured after administration of gamma-L-glutamyl-5-hydroxy-L-tryptophan only. The net effect of the concomitant infusion of both glutamyl derivatives was an increase in urinary sodium excretion. 4. Our study in salt-replete individuals suggests that dopamine rather than 5-hydroxytryptamine was preferentially produced when equimolar amounts of their precursors were provided and that the natriuretic effect of dopamine, generated intrarenally from gludopa, was greater than the sodium retaining action of 5-hydroxytryptamine derived from gamma-L-glutamyl-5-hydroxy-L-tryptophan. Comparison of the urinary metabolite data after the separate and concomitant infusion of the two glutamyl compounds provided no evidence of competitive inhibition of synthesis of either amine.
|
10.1042/cs0910177
|
pubmed_821_11551
|
Following thrombolysis and primary percutaneous transluminal coronary angioplasty (PTCA) for acute ST segment elevation myocardial infarction, basal flow in the culprit artery is known to influence prognosis. The purpose of this study was to determine if differences exist in basal flow in culprit and nonculprit coronary arteries in patients with acute ST segment elevation myocardial infarction who were treated with thrombolysis or primary PTCA with stent implantation. Twenty patients were randomized to thrombolysis (with recombinant tissue plasminogen activator) and 24 to primary PTCA with stent implantation within 3 hours of onset of acute ST segment elevation myocardial infarction. Coronary angiography was performed 90-120 minutes after thrombolysis or immediately after PTCA with stent implantation and again at 18-36 hours after intervention in both groups. Patients who failed to achieve thrombolysis in myocardial infarction (TIMI) grade 2 or 3 flow were excluded. The corrected TIMI frame count was used as the index of basal coronary artery flow. Early after intervention the mean corrected TIMI frame count in the culprit coronary artery was significantly lower in the primary PTCA with stent group (27.4 +/- 7.7 frames) than in the thrombolysis group (39.8 +/- 10 frames, p < 0.001). Eight thrombolysis patients (40%) and 20 primary PTCA patients (83%, p < 0.01) achieved TIMI grade 3 flow early after intervention. By 18-36 hours after intervention there were no significant differences in the mean correct TIMI frame count between the thrombolysis and primary PTCA with stent groups. There were no significant differences in the mean corrected TIMI frame count between these two groups in the nonculprit coronary artery, either early after intervention or at 18-36 hours. In successfully reperfused coronary arteries following acute ST segment elevation myocardial infarction, primary angioplasty with stent implantation reestablished TIMI grade 2 or 3 flow faster and more effectively than thrombolysis did.
|
10.1177/000331970105200301
|
pubmed_217_17708
|
Fibrodysplasia ossificans progressiva (FOP; MIM #135100) is a debilitating genetic disorder of dysregulated cellular differentiation characterized by malformation of the great toes during embryonic skeletal development and by progressive heterotopic endochondral ossification postnatally. Patients with these classic clinical features of FOP have the identical heterozygous single nucleotide substitution (c.617G > A; R206H) in the gene encoding ACVR1/ALK2, a bone morphogenetic protein (BMP) type I receptor. Gene targeting was used to develop an Acvr1 knock-in model for FOP (Acvr1(R206H/+)). Radiographic analysis of Acvr1(R206H/+) chimeric mice revealed that this mutation induced malformed first digits in the hind limbs and postnatal extraskeletal bone formation, recapitulating the human disease. Histological analysis of murine lesions showed inflammatory infiltration and apoptosis of skeletal muscle followed by robust formation of heterotopic bone through an endochondral pathway, identical to that seen in patients. Progenitor cells of a Tie2(+) lineage participated in each stage of endochondral osteogenesis. We further determined that both wild-type (WT) and mutant cells are present within the ectopic bone tissue, an unexpected finding that indicates that although the mutation is necessary to induce the bone formation process, the mutation is not required for progenitor cell contribution to bone and cartilage. This unique knock-in mouse model provides novel insight into the genetic regulation of heterotopic ossification and establishes the first direct in vivo evidence that the R206H mutation in ACVR1 causes FOP.
|
10.1002/jbmr.1637
|
pubmed_94_1261
|
With more than 1,800,000 cases and 110,000 deaths globally, COVID-19 is one of worst infectious disease outbreaks in history. This paper provides a critical review of the available evidence regarding the lessons learned from the Chinese experience with COVID-19 prevention and management. The steps that have led to a near disappearance of new cases in China included rapid sequencing of the virus to establish testing kits, which allowed tracking of infected persons in and out of Wuhan. In addition, aggressive quarantine measures included the complete isolation of Wuhan and then later Hubei Province and the rest of the country, as well as closure of all schools and nonessential businesses. Other measures included the rapid construction of two new hospitals and the establishment of "Fangcang" shelter hospitals. In the absence of a vaccine, the management of COVID-19 included antivirals, high-flow oxygen, mechanical ventilation, corticosteroids, hydroxychloroquine, tocilizumab, interferons, intravenous immunoglobulin, and convalescent plasma infusions. These measures appeared to provide only moderate success. Although some measures have been supported by weak descriptive data, their effectiveness is still unclear pending well controlled clinical trials. In the end, it was the enforcement of drastic quarantine measures that stopped SARS-CoV-2 from spreading. The earlier the implementation, the less likely resources will be depleted. The most critical factors in stopping a pandemic are early recognition of infected individuals, carriers, and contacts and early implementation of quarantine measures with an organised, proactive, and unified strategy at a national level. Delays result in significantly higher death tolls.
|
10.1016/j.cjca.2020.04.010
|
pubmed_1111_10383
|
BACKGROUND
Family refusal is an important factor that limits the number of organ donations. Some studies from different centers have reported various reasons for family decisions of organ donation refusal. This study evaluated the reasons for organ donation refusal by family members covered in our organ procurement organization.
METHODS
This cross-sectional study was performed among families of potential organ donors who satisfied brain death criteria as identified between March 2009 and March 2010.
RESULTS
Among 125 potential donors 73 (58.4%) families refused donation. Their main reasons were as follows: lack of acceptance of brain death n=26 (35.6%), belief in miracle and patient recovery (n=22; 30.1), fear of gossip regarding sale rather than autonomous organ donation (n=11; 15.1%), and fear about deformation of the donor's body (n=9; 12.3%).
CONCLUSION
Family members play an important role in the final decision for organ donation. The general public should be encouraged to register their donation preferences in the case of brain death.
|
10.1016/j.transproceed.2011.01.022
|
pubmed_988_6222
|
After myocardial infarction there is an acute deterioration of the flow properties of blood. The present study was designed to test whether the abnormality persists. Blood and plasma viscosity, red cell aggregation and deformability, haematocrit, erythrocyte sedimentation rate, white cell count, cholesterol, and triglycerides were measured in 51 patients who had had a myocardial infarction 5.4 (mean) years before. Results in patients and controls were compared and matched pairs with identical cardiovascular risk factors were also selected. Blood viscosity and red cell aggregation were increased and red cell deformability was decreased in the 51 patients. The abnormalities were independent of the interval since infarction and persisted for years. The rheological abnormalities present after myocardial infarction are at least partly independent of the acute event and acute phase reactions. They contribute to the reduced perfusion of the microcirculation of the heart.
|
10.1136/hrt.64.4.248
|
pubmed_810_10469
|
BACKGROUND
Matrix metalloproteases (MMPs) have been implicated in the pathogenesis of acute coronary syndromes (ACS). However, little is known about the mechanisms responsible for MMP expression in ACS. C-reactive protein (CRP) not only is an independent risk factor for cardiovascular events, but also may exert direct pro-atherosclerotic effects. Therefore, we aimed at determining whether CRP might induce MMP-9 in two different experimental conditions: 1) smooth muscle cells (SMCs) in vitro, and 2) patients with ACS.
METHODS AND RESULTS
Effects of increasing concentrations of CRP on MMP-9 expression were evaluated in vitro in human SMCs. TIMP-1 protein expression, the selective inhibitor of MMP-9, was also evaluated. CRP dose-dependently induced MMP-9 expression in SMCs by promoting MMP-mRNA transcription, as well as MMP-9 secretion. In contrast, no differences were found for TIMP-1 protein expression. In vivo, MMP-9 and CRP levels were measured in blood samples obtained from the aorta (Ao) and the coronary sinus (Cs) of patients with normal coronary arteries (controls, n=21), stable angina (n=24), and ACS (n=30). Both MMP-9 and CRP plasma levels were significantly increased across the coronary circulation only in patients with ACS. Interestingly, a significant correlation between MMP-9 and CRP plasma levels was found.
CONCLUSIONS
CRP induced MMP-9 expression and activity in human SMCs in culture; patients presenting with ACS have increased transcoronary plasma levels of MMP-9 and CRP with a significant correlation between these two markers. This may explain the heightened risk of coronary events in subjects with elevated levels of CRP.
|
pubmed_810_10469
|
pubmed_507_11450
|
Protein kinase Cs (PKCs) play important roles in signal transduction, cell regulation, and tumor formation. In the present study, we analyzed the expression of PKCs in human hepatocellular carcinoma (HCC) tissues and explored their roles in the development of HCC. Real-time quantitative PCR and immunohistochemistry showed that PKCbeta and PKCtheta were down-regulated in HCC tissues. Reduced expression of PKCtheta is well correlated with the grade of cancer cells (p = 0.009), and the down-regulated expression of PKCbetaII is associated with HBV infection (p = 0.035). Our findings suggest particular roles of the two PKC isoenzymes in the hepatocarcinogenesis of human HCC.
|
10.1007/s12253-009-9228-z
|
pubmed_1050_62
|
Environmental factors, oxidation and microorganisms contamination, are the major causes for food spoilage, which leads to sensory features alteration, loss of quality, production of harmful chemicals and growth of foodborne pathogens capable to cause severe illness. Synthetic preservatives, traditional conserving methods and food packaging (FP), although effective in counteracting food spoilage, do not allow the real-time monitoring of food quality during storage and transportation and assent a relatively short shelf life. In addition, FP may protect food by the spoilage caused by external contaminations, but is ineffective against foodborne microorganisms. FP preservative functionalities could be improved adding edible natural antioxidants and antimicrobials, but such chemicals are easily degradable. Nowadays, thanks to nanotechnology techniques, it is possible to improve the FP performances, formulating and inserting more stable antioxidant/antimicrobial ingredients, improving mechanical properties and introducing intelligent functions. The state-of-the-art in the field of nanomaterial-based improved FP, the advantages that might derive from their extensive introduction on the market and the main concerns associated to the possible migration and toxicity of nanomaterials, frequently neglected in existing reviews, have been herein discussed.
|
10.1016/j.foodres.2020.109664
|
pubmed_755_7680
|
Among 6,035 people living in 3 villages from the area of La Kara (Togo), 984 randomized subjects were investigated to evaluate goiter prevalence and related etiologic factors. Creatinine and thiocyanates (SCN-) were measured in urine, thyroid hormones and TSH in plasma. Iodine was evaluated in urine, water, salt, soil, millet and sorgho. The amount of cassava was evaluated in food. Mean goiter prevalence was 32%, reaching to 45.9% in one village; urinary iodine remained in a low range (27.2 +/- 2.18 micrograms/g creatinine in adults, 34.3 +/- 6.7 in children--m +/- SEM) independently of the presence of endemic goiter. Urinary SCN- was increased. Low iodine values were found in food, salt, soil and water which contained few mineral elements except flour which was increased in the samples collected in one of the 3 villages. Cretinism was absent, T4, T3, TSH remained in a normal range. This study confirms a high prevalence of endemic goiter in the area of La Kara with iodine deficiency, leading to an urgent iodine supplementation.
|
pubmed_755_7680
|
pubmed_26_21311
|
Cytoreductive nephrectomy in combination with adjuvant immunotherapy is an established treatment option for selected patients with metastatic clear-cell renal cell carcinoma (mCC-RCC). Multitargeted antiangiogenic and mammalian target of rapamycin tyrosine kinase inhibitors (TKIs) are now established treatment paradigms in patients with mCC-RCC. Given that all the recent seminal TKI trials in mCC-RCC provide no evidence base for the use of cytoreductive nephrectomy in the TKI era, it is not presently clear where such a surgical approach fits into the treatment paradigm. This review summarizes the evidence for the management of mCC-RCC and outlines novel approaches to be tested within future trials if the initial proposed phase III trials in this setting, using sunitinib, are successful. Overall, two principal questions need addressing. First, is cytoreductive nephrectomy necessary in the TKI era? Second, if so, what is the most appropriate scheduling of TKI therapy with cytoreductive nephrectomy?
|
10.1634/theoncologist.2008-0121
|
pubmed_123_9207
|
A mechanism-based dosimetry model was developed to describe 2,4,4-trimethyl-2-pentanol (TMP-2-OH) dosimetry and renal alpha 2u-globulin (alpha 2u) nephropathy in the male Fischer 344 rat. Experimental data were collected to estimate the chemical-specific parameters (metabolic constants, tissue solubility, and oral absorption rate) necessary to describe TMP-2-OH dosimetry in male rats. The concentrations of alpha 2u and TMP-2-OH were measured in male rats up to 64 hr after a single oral dose of TMP-2-OH (6, 60, or 600 mg/kg). The model predicted the time course behavior of TMP-2-OH and alpha 2u in the kidney, but overestimated their renal concentrations by two or threefold. Simulations of renal alpha 2u concentration were sensitive to changes in TMP-2-OH-alpha 2u-binding affinity and degradation rate of the TMP-2-OH-protein complex. In contrast, simulation of the concentration of TMP-2-OH in the kidney was most sensitive to the amount of protein present. Oral absorption of TMP-2-OH was dose dependent. The model predicted that alpha 2u and TMP-2-OH concentration in the kidney is sensitive to changes in the rate of TMP-2-OH absorbed after oral administration. This model permitted a more rigorous evaluation than has previously been possible of the combination of protein characteristics and chemical dosimetry required for the accumulation of alpha 2u in the kidney of male rats. The behavior of the model is consistent with the qualitative aspects of the alpha 2u hypothesis. However, further characterization of alpha 2u distribution and renal hydrolysis will be required in order to fully characterize the hypothesis at the quantitative level.
|
10.1006/faat.1995.1046
|
pubmed_440_2557
|
Objective The aims of the present study were to establish rates of resuscitation order documentation of patients aged ≥65 years from both psychogeriatric and general medical units and to compare patients on predictors of resuscitation status, particularly examining the effect of depression. Methods A retrospective case note audit of psychogeriatric (n=162) and general medical (n=135) unit admissions within a tertiary teaching hospital was performed. Multivariate logistic regression was used to determine significant clinical and demographic predictors of resuscitation status. Results Resuscitation orders were documented in more psychogeriatric (94.4%) than general medical (48.1%) files. Depression did not significantly predict resuscitation status in either group. Having undergone competency assessment significantly predicted resuscitation status for the total sample and separately for psychogeriatric and medical patients. Older age (overall sample), poorer prognosis (overall sample), living in residential care (overall sample and medical group) and self-consenting to resuscitation status (overall sample and medical group) significantly predicted resuscitation status. Conclusions Resuscitation orders were more frequently documented on the psychogeriatric unit. Further prospective analysis is needed of how resuscitation orders are made before depression is discounted as a predictor of end-of-life decision-making. What is known about the topic? Despite increased community, media and research attention to end-of-life decision-making, resuscitation preferences of older patients are often poorly documented. Existing research into patient clinical and demographic factors that influence end-of-life decision-making have largely focused on general medical rather than psychogeriatric settings. There is a need to investigate rates of resuscitation documentation in psychogeriatric and general medical units and specific factors associated with having a 'do not attempt resuscitation' order in place, particularly the effect of current depression on decision-making. What does this paper add? Resuscitation orders were more frequently documented on the psychogeriatric than medical unit. Depression was not a significant predictor of resuscitation status in either group of patients. Although having undergone a competency assessment, older age and poorer prognosis predicted not being for resuscitation for the total sample, living in residential care and self-consenting to resuscitation status predicted not being for resuscitation for the overall sample and the medical group specifically. What are the implications for practitioners? This paper suggests that the need for clinicians to ensure documentation of preferences is a focus of day-to-day work with older patients. Clinicians should consider patient competency in end-of-life decision-making and how factors associated with depression, such as helplessness, may be more closely related to resuscitation decision-making in older patients.
|
10.1071/AH18004
|
pubmed_821_16341
|
Myelosuppression is commonly observed after alkylating agent chemotherapy due to low levels of O(6)-alkylguanine DNA alkyltransferase protein (AGT) in hematopoietic progenitors. Mice that lack AGT in all organs, O(6)-methylguanine-DNA methyltransferase gene knockout (MGMT(-/-)) mice are extremely hypersensitive to the methylating agent N-methyl-N-nitrosourea (MNU) and exhibit a 10-fold reduction in the LD(90). To determine whether bone marrow damage was the cause of the increased lethality, we transplanted 1 x 10(6) wild-type marrow into MGMT(-/-) mice and MGMT(-/-) marrow into wild-type mice and observed survival after MNU. Lethally irradiated MGMT(-/-) mice given > or = 25 mg/kg MNU 3 weeks after transplant of wild-type cells survived > 30 days (n = 11), whereas this dose was lethal to control MGMT(-/-) mice 9-12 days post treatment (n = 5). Conversely, lethally irradiated wild-type mice transplanted with MGMT(-/-) cells died after only 20-60 mg/kg MNU within 8-12 days (n = 6). No significant toxicities were found in other organs. Additionally, in an in vivo post transplant competition model, wild-type long-term repopulating cells had a > 200-fold competitive survival advantage over MGMT(-/-) cells, and after MNU treatment completely repopulated the mouse when transplanted at only one-tenth the cell number. We also observed a strong selection for transplanted marrow-derived wild-type stromal elements in the MGMT(-/-) background after drug treatment. These data indicate that alkylating agent hypersensitivity of MGMT(-/-) mice results from hematopoietic damage at the stem level. Thus, DNA repair involving AGT in hematopoietic cells is required for normal host survival following exposure to methylating and chloroethylating agents.
|
10.1089/152581601750098354
|
pubmed_75_11916
|
Measurements of the K activity (aiK) in ferret ventricle were made using either single- or double-barrelled K-sensitive micro-electrodes. aiK was also estimated from the Nernst equation by measuring the membrane potential when changing the external K concentration. Micro-electrodes filled with the Corning K sensor gave unreliable results most probably due to interference from some substance(s) in the heart cells. Reproduceable measurements were obtained using a valinomycin cocktail as the K sensor. The mean value +/- S.D. for aiK from four experiments which met strict criteria for calibration, electrode penetration and drift was 104 mmol/l +/- 9 mmol/l. If all nine experiments were taken the value was 101 mmol/l +/- 8 mmol/l. Estimation from the Nernst equation gave values of aiK that were on average 20 mmol/l higher than the measured values with the valinomycin cocktail. It is recommended that a valinomycin cocktail be used to measure aiK.
|
10.1113/expphysiol.1986.sp003004
|
pubmed_765_2494
|
BACKGROUND
Asbestos-related lung diseases are one of the leading diagnoses of the recognized occupational diseases in Germany, both in terms of their number and their socio-economic costs. The aim of this study was to determine whether pulmonary function testing (spirometry and CO diffusion measurement (DLCO)) and computed tomography of the thorax (TCT) are relevant for the early detection of asbestos-related pleural and pulmonary fibrosis and the assessment of the functional deficiency.
METHODS
The records of 111 formerly asbestos-exposed workers who had been examined at the Institute for Occupational and Maritime Medicine, Hamburg, Germany, with data on spirometry, DLCO and TCT were reviewed. Workers with substantial comorbidities (cardiac, malignant, silicosis) and/or pulmonary emphysema (pulmonary hyperinflation and/or TCT findings), which, like asbestosis, can lead to a diffusion disorder were excluded. The remaining data of 41 male workers (mean 69.8 years ±6.9) were evaluated. The TCT changes were coded according to the International Classification of High-resolution Computed Tomography for Occupational and Environmental Respiratory Diseases (ICOERD) by radiologists and ICOERD-scores for pleural and pulmonary changes were determined. Correlations (ρ), Cohens κ and accuracy were calculated.
RESULTS
In all 41 males the vital capacity (VC in % of the predicted value (% pred.)) showed only minor limitations (mean 96.5 ± 18.0%). The DLCO (in % pred.) was slightly reduced (mean 76.4 ± 16.6%; median 80.1%); the alveolar volume related value (DLCO/VA) was within reference value (mean 102 ± 22%). In the TCT of 27 workers pleural asbestos-related findings were diagnosed whereof 24 were classified as pulmonary fibrosis (only one case with honey-combing). Statistical analysis provided low correlations of VC (ρ = - 0.12) and moderate correlations of DLCO (- 0.25) with pleural plaque extension. The ICOERD-score for pulmonary fibrosis correlated low with VC (0.10) and moderate with DLCO (- 0.23); DLCO had the highest accuracy with 73.2% and Cohens κ with 0.45. DLCO/VA showed no correlations to the ICOERD-score. The newly developed score, which takes into account the diffuse pleural thickening, shows a moderate correlation with the DLCO (ρ = - 0.35, p < 0.05).
CONCLUSIONS
In formerly asbestos-exposed workers, lung function alterations and TCT findings correlated moderate, but significant using DLCO and ICOERD-score considering parenchymal ligaments, subpleural curvilinear lines, round atelectases and pleural effusion in addition to pleural plaque extension. DLCO also showed highest accuracy in regard to pulmonary findings. However, VC showed only weaker correlations although being well established for early detection. Besides TCT the determination of both lung function parameters (VC and DLCO) is mandatory for the early detection and assessment of functional deficiencies in workers formerly exposed to asbestos.
|
10.1186/s12995-020-00272-1
|
pubmed_723_22735
|
OBJECTIVE
Renal cancer is one of the most deadly urological malignancies. Currently, there is still a lack of effective treatment. Our purpose was to explore the mechanisms of miR-122-5p in renal cancer.
METHODS
The expression levels of miR-122-5p and pyruvate kinase M2 (PKM2) in renal cancer cells were detected by RT-qPCR and Western blot analyses, respectively. Then, we measured the cell viability after knockdown of miR-122-5p and PKM2 using CCK-8 assay. Moreover, flow cytometry was used to investigate cell cycle and apoptosis of renal cancer cells. The cell migration of renal cancer cells transfected by miR-122-5p inhibitor and siPKM2 was then detected by wound healing assay. Furthermore, glucose consumption and lactate production were measured. Autophagy-related protein LCII/I was detected by Western blot.
RESULTS
MiR-122-5p was upregulated in renal cancer cells compared to HK2 cells, especially in 786-O cells. We found that silencing miR-122-5p promoted PKM2 expression in 786-O cells. After transfection of siPKM2 or miR-122-5p inhibitor, the cell viability of 786-O cells was significantly reduced. Furthermore, the G1 phase of 786-O cells was significantly blocked, and the S phase was significantly increased. In addition, knockdown of miR-122-5p or PKM2 promoted renal cancer cell apoptosis and inhibited cell migration. Glucose consumption of 786-O cells was significantly increased after transfection by siPKM2. Silencing miR-122-5p significantly promoted the expression levels of LCII/I.
CONCLUSION
Our findings revealed that overexpressed miR-122-5p promotes renal cancer cell viability, proliferation, migration, glycolysis and autophagy by negatively regulating PKM2, which provide a new insight for the development of renal cancer therapy.
|
10.2147/CMAR.S225742
|
pubmed_674_15299
|
OBJECTIVE
Microstructural changes in dentin carious lesions were investigated using a 3D laser scanning microscope, which has a morphological theoretical foundation in the further study of clinical caries disease prevention and treatments.
METHODS
Six fresh extracted caries molars were prepared into cross-section specimens. The sections were examined by 3D and laser measuring morphology.
RESULTS
Zones were identified in the lesions on the basis of their optical appearance. Two zones were identified in the lesions on the basis of their laser appearance. The microstructure showed that the tubular was partly closed in transparent dentin; peritubular and intertubular dentin were reduced in the zone of demineralization; peritubular and intertubular dentin were damaged and fused; a beaded sample and oval lesions formed in the zone of bacterial invasion; and abnormal dentin structure was present in the zone of destruction on the basis of their laser appearance. Four zones were iden-tified in the lesions according to their colors, as determined from their 3D appearance.
CONCLUSIONS
3D laser scanning micros-cope may be a powerful, accessible, and non-destructive technique, as it identified the lesion and tubular zones, as well as peritubular and intertubular dentin in the four zones' lesions. The microstructure of dentin caries lesions may have significant merit in the evaluation of clinical prevention and treatment.
|
10.7518/hxkq.2016.05.017
|
pubmed_702_16639
|
Careful regulation of the body's immunoglobulin-G (IgG) and albumin concentrations is necessitated by the importance of their respective functions. As such, the neonatal Fc receptor (FcRn) which, as a single receptor, is capable of regulating both of these molecules, has become an important focus of investigation. In addition to these essential protection functions, FcRn possesses a host of other functions that are equally as critical. During the very first stages of life, FcRn mediates the passive transfer of IgG from mother to offspring both before and after birth. In the adult, FcRn regulates the persistence of both IgG and albumin in the serum as well as the movement of IgG, and any bound cargo, between different compartments of the body. This shuttling allows for the movement not only of monomeric ligand but also of antigen/antibody complexes from one cell type to another in such a way as to facilitate the efficient initiation of immune responses towards opsonized pathogens. As such, FcRn continues to play the role of an immunological sensor throughout adult life, particularly in regions such as the gut which are exposed to a large number of infectious antigens. Increasing appreciation for the contributions of FcRn to both homeostatic and pathological states is generating an intense interest in the potential for therapeutic modulation of FcRn binding. A greater understanding of FcRn's pleiotropic roles is thus imperative for a variety of therapeutic purposes.
|
10.1007/s00281-009-0160-9
|
pubmed_573_10298
|
Control strategies to minimize mycotoxin levels in food comprise several broad categories, including good agricultural practice, good manufacturing practice, and hazard analysis and critical control point principles. In general, intervention strategies include pre-harvest, post-harvest, and dietary approaches, depending on the specific mycotoxins and the food commodity likely to be contaminated. This chapter describes practical interventions, which are arranged by the major groups of mycotoxins and are described according to their stage of development, efficacy, geographical regions in which they have been tested or applied, simplicity or complexity, and breadth of usefulness. Typical pre-harvest interventions include the breeding of resistant plant cultivars, good agricultural practice, and biocontrol using non-toxigenic strains. Post-harvest interventions include the removal of infected and/or insect-damaged food components by sorting, maintaining correct drying and storage conditions, and chemical deactivation such as nixtamalization. Dietary interventions include reducing mycotoxin bioavailability or modulating metabolism in ways that reduce the harmful effects of reactive metabolites. Cost-effective and simple intervention methods, predominantly at the population level, should be emphasized in developing countries, where resources are limited and sophisticated technologies are lacking.
|
pubmed_573_10298
|
pubmed_1133_1467
|
PURPOSE
The purpose of this study is to assess in vivo whether diagnostic lumbar puncture (LP) is followed by optic nerve head (ONH) and parapapillary anatomic changes in normal human eyes.
MATERIALS AND METHODS
Prospective, single-center, observational case series. ONH structures (prelaminar tissue surface, anterior surface of the lamina cribrosa, central retinal vessels) and parapapillary structures (internal limiting membrane, posterior surfaces of retinal nerve fiber layer and Bruch membrane/retinal pigment epithelium complex, Bruch membrane opening, posterior surface of the choroid) were quantitatively evaluated by means of swept-source optical coherence tomography (Triton Ver.10.05, Topcon, Tokyo, Japan) before and after LP (5, 60, and 360 min). Each of these structures was manually delineated for measurement before being superimposed to detect any displacement, using peripheral margins of parapapillary structures as a reference plane.
RESULTS
A total of 16 eyes of 8 nonglaucomatous patients were evaluated. The CSF volume was median (IQR), 1.65 mL (1.16 to 2.00) and none of the ONH structures showed any anatomic changes at any time point after LP.
CONCLUSIONS
According to the design of this study, diagnostic LP is a safe procedure regarding deep ONH structures in nonglaucomatous subjects.
|
10.1097/IJG.0000000000000752
|
pubmed_1042_22122
|
Antibiotic resistance has become a major concern for human and animal health. As fluoroquinolones have been extensively used in human and veterinary medicine, there has also been the rapid emergence and spread of antimicrobial resistance around the world. Here, we analysed the microbiome of goat milk using samples from healthy goats and those diagnosed with persistent mastitis and treated using the antibiotic enrofloxacin with 16S rRNA amplicon sequencing. We selected a group of 11 goats and 22 samples of milk that did not respond clinically to enrofloxacin treatment. Milk samples were evaluated before and after treatment to verify changes of the microbiota; the three first lactating goats were selected from the healthy control group. The milk samples from the healthy control animals presented a larger abundance of different species of bacteria of the Staphylococcus genus, but a smaller number of different genera, which indicated a more specific niche of resident bacteria. The Firmicutes phylum was predominantly different between the studied groups. Samples from before-treatment animals had a higher number of new species than those from the control group, and after being treated again. These microbiota received new bacteria, increasing the differences in bacteria even more in relation to the control group. Genotypes such as Trueperella and Mannheimia, between other genera, had a high abundance in the samples from animals with persistent mastitis. The dysbiosis in this study, with marked evidence of a complex microbiota in activity in cases of the failure of antimicrobial treatment for persistent chronic mastitis, demonstrates a need to improve the accuracy of pathogen identification and increases concern regarding antibiotic treatments in milk production herds.
|
10.1038/s41598-020-61407-2
|
pubmed_884_6049
|
The effects of inhalation and cutaneous exposure to styrene on the drug metabolizing enzymes were studied in the rat. Rats were exposed eight hours per day, for seven successive days to 450 ppm concentration of styrene or received one cutaneous dose of styrene daily for seven consecutive days (0.5 and 3.0 g/kg). The animals were killed one day after the last dose. Styrene inhalation increased the activities of epoxide hydrase and UDPglucuronosyltransferase (4-methylumbelliferone as substrate) in liver (1.5- and 1.7-fold, respectively). Ethoxycoumarin deethylation was enhanced 1.7-fold in the kidney. The content of cytochrome P-450 in the liver and the activities of NADPH cytochrome c-reductase, benzpyrene hydroxylase and glutathione S-transferase in the liver and kidney were not altered. No changes in the enzyme activities were detected in the lung. Styrene depressed the epoxide hydrase activity in liver when administered cutaneously. No signs of enzyme induction could be seen after cutaneous administration.
|
pubmed_884_6049
|
pubmed_770_7666
|
Data presented in this study highlight the potential of allozyme electrophoresis in providing unequivocal genetic evidence for the identification of life cycle stages, particularly where species have complex life cycles. Adults of the nematode Echinocephalus overstreeti parasitize the elasmobranch Heterodontus portusjacksoni. The putative larval form which is morphologically dissimilar is found in two species of marine molluscs, Chlamys bifrons and Pecten albus. Electrophoretic analysis indicated that the adult and larval forms shared alleles at all of the 34 enzyme loci established. Furthermore, there were no fixed allelic differences between larval forms from different mollusc species.
|
10.1017/s0022149x0001141x
|
pubmed_440_15763
|
The parboilization of rice generates 2 L of effluent per kilogram of processed grain. Several methodologies have previously been tested with the aim of reducing the environmental impact of this effluent. The objective of this study was to evaluate the bioremediation of parboiled rice effluent supplemented with sucrose or residual glycerol from the biodiesel during the cultivation of the Saccharomyces boulardii probiotic. In the first stage of the experiment, cultures were grown in orbital shaker, and five media compositions were evaluated: 1) parboiled rice effluent; 2) effluent supplemented with 1% sucrose; 3) effluent supplemented with 3% sucrose; 4) effluent supplemented with 15 g.L-1 of biodiesel glycerol and 5) standard yeast culture medium (YM). The addition of 1% of sucrose generated the most promising results in terms of cell viability, removal of nitrogen, phosphorus and chemical oxygen demand (COD). From these results, four independent cultures were grown in a bioreactor using effluent +1% of sucrose as the medium. This assays generated a mean of 3.8 g.L-1 of biomass, 1.8 × 1011 CFU.L-1, and removal of 74% of COD and 78% of phosphorus. Therefore, the cultivation of Saccharomyces boulardii in parboiled rice effluent supplemented with 1% sucrose may represent a viable method by which the environmental impact of this effluent can be reduced while simultaneously producing probiotic culture for use in animal production.
|
10.1016/j.jenvman.2018.08.027
|
pubmed_1102_18939
|
Postpartum uterine infections are common reproductive diseases in postpartum cows. Evidence has shown that plasma β-endorphins increase during bovine uterine inflammation. However, the effect of β-endorphins on the inflammatory response in bovine endometrium has not been clarified. The aim of this study was to investigate the effect of β-endorphins on the inflammatory response of bovine endometrial epithelial and stromal cells, and to explore the possible mechanism. The cells were treated with E. coli lipopolysaccharide (LPS) to simulate inflammation, which was characterized by the significant activation of NF-κB signaling pathway and the increased gene expression of the downstream proinflammatory cytokines (approximately 1.2- to 15-fold increase, P < 0.05). By using Western blot and qPCR techniques, we found that β-endorphins inhibited the key protein expression of NF-κB pathway, and the gene expressions of TNF, IL1B, IL6, CXCL8, nitric oxide synthase 2, and prostaglandin-endoperoxide synthase 2 (P < 0.05). The co-treatment of β-endorphins and opioid antagonists showed that the anti-inflammatory effect of β-endorphins could be blocked (P < 0.05) by non-selective opioid antagonist naloxone or δ opioid receptor antagonist ICI 154129, but not the μ opioid receptor antagonist CTAP (P > 0.05). In conclusion, β-endorphins may inhibit the inflammatory response of bovine endometrial epithelial and stromal cells through δ opioid receptor.
|
10.1016/j.dci.2021.104074
|
pubmed_564_13571
|
Crohn's disease is associated with a hypercoagulable state due to platelet or clotting abnormalities which may be responsible for the thromboembolic episodes seen in this condition. We report the occurrence of anticardiolipin antibodies in a patient with Crohn's disease who presented with Amaurosis fugax and suggest that these antibodies may be a further cause of the hypercoagulable state of Crohn's disease in some patients.
|
10.1177/096120339300200116
|
pubmed_910_6761
|
Transanal, hybrid natural orifice translumenal endoscopic surgery (NOTES) and NOTES-assisted natural orifice specimen extraction techniques hold promise as leaders in the field of natural orifice surgery. We report the feasibility of a novel NOTES assisted technique for unlimited length, clean, endolumenal proctocolectomy in a porcine model. This technique is a modification of a transanal intussusception and pull-through procedure recently published by our group. Rectal mobilization was achieved laparoscopically; this was followed by a transanal recto-rectal intussusception and pull-through (IPT). IPT was established in a stepwise fashion. First, the proximal margin of resection was attached laparoscopically to the shaft of the anvil of an end-to-end circular stapler with a ligature around the rectum. Second, this complex was pulled transanally to produce IPT. To achieve an unlimited-length proctocolectomy, the IPT step was repeated several times prior to bowel resection. This was facilitated by removing the ligature applied in the first step of this procedure. Once sequential IPT established the desired length of bowel to be resected, a second ligature was placed around the rectum approximating the proximal and distal resection margins. The specimen was resected and extracted by making a full-thickness incision through the 2 bowel walls. The anastomosis was achieved by deploying the stapler. The technique was found to be feasible. Peritoneal samples, collected after transanal specimen extraction, did not demonstrate bacterial growth. The minimally invasive nature of this evolving technique as well as its aseptic bowel manipulation has the potential to limit the complications associated with abdominal wall incision and surgical site infection.
|
10.1177/1553350616643614
|
pubmed_634_23061
|
Checkpoint kinase 2 (Chk2) is a pivotal effector kinase in the DNA damage response, with an emerging role in mitotic chromosome segregation. In this study, we show that Chk2 interacts with myosin phosphatase targeting subunit 1 (MYPT1), the targeting subunit of protein phosphatase 1cβ (PP1cβ). Previous studies have shown that MYPT1 is phosphorylated by CDK1 at S473 during mitosis, and subsequently docks to the polo-binding domain of PLK1 and dephosphorylates PLK1. Herein we present data that Chk2 phosphorylates MYPT1 at S507 in vitro and in vivo, which antagonizes pS473. Chk2 inhibition results in failure of γ-tubulin recruitment to the centrosomes, phenocopying Plk1 inhibition defects. These aberrancies were also observed in the MYPT1-S507A stable transfectants, suggesting that Chk2 exerts its effect on centrosomes via MYPT1. Collectively, we have identified a Chk2-MYPT1-PLK1 axis in regulating centrosome maturation. Abbreviations: Chk2: checkpoint kinase 2; MYPT1: myosin phosphatase targeting subunit 1; PP1cβ: protein phosphatase 1c β; Noc: nocodazole; IP: immunoprecipitation; IB: immunoblotting; LC-MS/MS: liquid chromatography-tandem mass spectrometry; Chk2: checkpoint kinase 2; KD: kinase domain; WT: wild type; Ub: ubiquitin; DAPI: 4',6-diamidino-2-phenylindole; IF: Immunofluorescence; IR: ionizing radiation; siCHK2: siRNA targeting CHK2.
|
10.1080/15384101.2019.1654795
|
pubmed_889_22221
|
Aberrantly activated Wnt signaling pathway and dysregulation of extracellular antagonists of Wnt signaling have been revealed in pulmonary fibrosis. In this study we evaluated the expression of secreted frizzled-related proteins (SFRPs) and their aberrant promoter methylation to investigate the involvement of epigenetic regulation in pulmonary fibrosis. The pulmonary fibrosis induced by intratracheal injection of bleomycin (BLM) into mice was adopted. The transcription and relative protein expression of SFRPs were detected at Day 7 (D7), D14, and D21. DNA methylation analysis was performed by methylation-specific polymerase chain reaction (MSP). A DNA methyltransferase (DNMT) inhibitor (5-aza-2'-deoxycytidine; 5-aza) was used for demethylation and the relative β-catenin expression levels were measured to assess overactivity of the canonical Wnt signaling pathway. The transcription and protein expression of SFRP1 significantly decreased at D14 and D21, whereas the transcription and protein expression of SFRP4 significantly decreased at D7 and stayed downregulated until D21. The significantly hypermethylated promoters of SFRP1 and SFRP4 resulted in impaired transcription and decreased expression during pulmonary fibrosis in mice. Besides, reactivation of SFRP1 and SFRP4 by 5-aza reduced β-catenin mRNA and protein expression in vivo and in vitro. Animal experiments confirmed that 5-aza could significantly alleviate bleomycin-induced pulmonary fibrosis in mice. Thus, changes of promoter hypermethylation might downregulate SFRP1 and SFRP4 at different stages of pulmonary fibrosis, and the finding supports the usefulness of DNMT inhibitors, which might effectively reverse activation of β-catenin and reduce pulmonary fibrosis in mice. These data provide a possible new direction in the research on pulmonary fibrosis treatments.
|
10.1016/j.lfs.2018.12.041
|
pubmed_787_4302
|
This study was conducted to determine the relationship among temperatures measured at different anatomical sites of the animal body and their daily pattern as indicative of the thermal stress in lactating dairy cows under tropical conditions. Environmental dry bulb (DBT) and black globe (BGT) temperatures and relative humidity (RH) were recorded. Rectal temperature (RT), respiratory frequency (RF), body surface (BST), internal base of tail (TT), vulva (VT) and auricular temperatures (AT) were collected, from 37 Black and White Holstein cows at 0700, 1300 and 1800 hours. RT showed a moderately and positive correlations with all body temperatures, ranging from 0.59 with TT to 0.64 with BST. Correlations among AT, VT and TT with RF were very similar (from 0.63 to 0.64) and were greater than those observed for RF with RT (0.55) or with BST (0.54). RF and RT were positively correlated to TT (0.63 and 0.59, respectively), AT (r = 0.63 for both) and VT (r = 0.64 and 0.63, respectively). Positive and very high correlations were observed among AT, VT and TT (from 0.94 to 0.97) indicating good association of temperatures measured in these anatomical sites. Correlations of BST with AT and VT were positive and very similar (0.71 and 0.72, respectively) and lower with TT (0.66). The AT, TT, VT and BST presented similar patterns and follow the variations of DBT through the day. Temperatures measured at different anatomical sites of the animal body have the potential to be used as indicative of the thermal stress in lactating dairy cows.
|
10.1007/s00484-009-0268-6
|
pubmed_507_11011
|
CONTEXT
Although recent trends in obesity have been well documented, generational patterns of obesity from early childhood through adulthood across birth cohorts, which account for the recent epidemic of childhood obesity, have not been well described. Such trends may have implications for the prevalence of obesity-associated conditions among population subgroups, including type 2 diabetes.
OBJECTIVE
Our objective was to evaluate trajectories of obesity over the life course for the US population, overall and by gender and race.
DESIGN, SETTING AND PARTICIPANTS
We conducted an age, period and birth cohort analysis of obesity for US individuals who participated in the National Health and Nutrition Examination Surveys (NHANES) (1971-2006).
MAIN OUTCOME MEASURES
Obesity was defined as a body mass index >or=95th percentile for individuals aged 2-16 years or >or=30 kg m(-2) among individuals older than 16 years. Age was represented by the age of the individual at each NHANES, period was defined by the year midpoint of each survey, and cohort was calculated by subtracting age from period.
RESULTS
Recent birth cohorts are becoming obese in greater proportions for a given age, and are experiencing a greater duration of obesity over their lifetime. For example, although the 1966-1975 and 1976-1985 birth cohorts had reached an estimated obesity prevalence of at least 20% by 20-29 years of age, this level was only reached by 30-39 years for the 1946-1955 and 1956-1965 birth cohorts, by 40-49 years for the 1936-1945 birth cohort and by 50-59 years of age for the 1926-1935 birth cohort. Trends are particularly pronounced for female compared with male, and black compared with white cohorts.
CONCLUSIONS
The increasing cumulative exposure to excess weight over the lifetime of recent birth cohorts will likely have profound implications for future rates of type 2 diabetes, and mortality within the US population.
|
10.1038/ijo.2009.235
|
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.