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pubmed_937_4832 | The functional groups of the DNA methylation site that are involved in the DNA interaction with methyltransferase SsoII at the recognition stage were identified. The contacts in the enzyme-substrate complex were analyzed in the presence of S-adenosyl-L-homocysteine using the interference footprinting assay with formic acid, hydrazine, dimethyl sulfate, or N-ethyl-N-nitrosourea as a modifying reagent. It was shown that the replacement of the central A.T by the G.C pair in the methylation site did not affect the enzyme-DNA interaction, whereas the use of a substrate with one chain methylated (monomethylated substrate) instead of the unmethylated substrate dramatically changes the DNA contacts. The binding constants of unmethylated and monomethylated substrates with methyltransferase SsoII in the presence of S-adenosyl-L-homocysteine were calculated. | 10.1023/a:1020463810179 |
pubmed_33_22418 | Osteomalacia is a metabolic bone disease that leads to softening of the bones and can be caused by hypophosphatemia. Large clinical studies of low-dose adefovir dipivoxil (adefovir) have found no evidence of renal tubular dysfunction leading to hypophosphatemia after 48 weeks of treatment. We report two cases of low-dose adefovir-induced hypophosphatemic osteomalacia that initially presented with diffuse musculoskeletal pain. The first patient was a 62-year-old man with a 2-year history of bone pain involving the dorsal mid-thorax, lower anterior chest wall, right sacroiliac joint area, and both knees. The patient had been receiving adefovir for 5 years before confirmation of hypophosphatemia and urinary phosphate wasting. Bone scintigraphy revealed multifocal lesions including multiple ribs, costochondral junctions, costovertebral junctions, sacrum, both posterior iliac bones, both proximal tibia, right calcaneus, and the left second metatarsophalangeal joint area, which were suggestive of metabolic bone disorder. Bone pain was significantly reduced within 3 months after supplementation with phosphate and calcitriol. The second patient was a 54-year-old male who presented with an 18-month history of severe bone pain of the right medial knee and low back. The patient had been taking adefovir for approximately 40 months before the development of bone pain. Laboratory data revealed hypophosphatemia and vitamin D deficiency. Bone scintigraphy showed increased uptake in bilateral ribs, sternum, both scapulae, both costovertebral junctions, both pelvic bones, medial cortex of the right proximal femur, right proximal tibia, and the left lateral tarsal bone. The symptoms improved by changing the antiviral agent from adefovir to entecavir. Because osteomalacia often presents with diffuse bone pain, non-specific radiologic findings and non-characteristic routine serum biochemical changes, the disease can be confused with various musculoskeletal diseases and a high index of suspicion is necessary for an early diagnosis in patients receiving adefovir therapy. | 10.1007/s00774-012-0384-y |
pubmed_757_6595 | The biologically important, FAD-containing acyl-coenzyme A (CoA) dehydrogenases (ACAD) usually catalyze the anti-1,2-elimination of a proton and a hydride of aliphatic CoA thioesters. Here, we report on the structure and function of an ACAD from anaerobic bacteria catalyzing the unprecedented 1,4-elimination at C3 and C6 of cyclohex-1-ene-1-carboxyl-CoA (Ch1CoA) to cyclohex-1,5-diene-1-carboxyl-CoA (Ch1,5CoA) and at C3 and C4 of the latter to benzoyl-CoA. Based on high-resolution Ch1CoA dehydrogenase crystal structures, the unorthodox reactivity is explained by the presence of a catalytic aspartate base (D91) at C3, and by eliminating the catalytic glutamate base at C1. Moreover, C6 of Ch1CoA and C4 of Ch1,5CoA are positioned towards FAD-N5 to favor the biologically relevant C3,C6- over the C3,C4-dehydrogenation activity. The C1,C2-dehydrogenation activity was regained by structure-inspired amino acid exchanges. The results provide the structural rationale for the extended catalytic repertoire of ACADs and offer previously unknown biocatalytic options for the synthesis of cyclic 1,3-diene building blocks. | 10.1002/cbic.202100421 |
pubmed_1086_4773 | OBJECTIVE
To evaluate the wear patterns of orthodontic archwires in dry and wet conditions in-vitro.
METHODS
The patterns of wear of stainless steel and NiTi orthodontic archwires were investigated with a fretting wear tribometer fitted with an alumina ball. The tribometer was operated at 23 degrees C in three different environments: ambient air with 50 per cent relative humidity (RH), 0.9 wt. per cent sodium chloride solution and deionised water. Differences in the wear characteristics of the archwires were investigated by scanning electron microscopy. Energy Dispersive X-ray Analysis and Inductively Coupled Plasma Analysis were used to investigate the surface composition of the wires, the wear debris generated during fretting and the corrosion products in the test solutions.
RESULTS
Both archwire materials were degraded by oxidational wear in ambient air. The NiTi wires were more resistant to wear than the stainless steel wires. In the aqueous media the stainless steel wires were degraded by abrasive wear, while the NiTi wires were degraded by adhesive wear.
CONCLUSION
In ambient air with 50 per cent RH, NiTi wires were more resistant to wear than stainless steel wires. Both archwire materials exhibited higher wear rates in the solutions than in air, indicating some synergism between the wear and corrosion processes. In the solutions the stainless steel archwires had a much lower corrosion-wear resistance than the NiTi archwires. | pubmed_1086_4773 |
pubmed_372_3236 | Appropriate knowledge, practice, and availability of iodized salt are used to eliminate iodine deficiency disorders. However, little is known about the availability of adequately iodized salt in the western part of Ethiopia. Thus, the aim of this study was to assess knowledge, practice, and availability of iodized salt and associated factors at household level in Jibat woreda, Ethiopia. Community-based cross-sectional study was conducted using structured and pretested questionnaire interview. Sampling salt was tested by the iodometric titration method. The result showed that iodine content more than 90% was considered as adequately iodized salt. The result of this study shown that among the 357 salt samples, 191(53.5%) households had good knowledge on iodized salt while 166 (46.5%) had poor knowledge on iodized salt. In addition, the result of the study revealed that 162 (45.4%) had good practice of iodized salt, whereas 195 (54.6%) had poor practice of iodized salt. The result of this study also shown that 149 (41.7%) households were using adequately iodized salt while 208 (58.3%) were using inadequate iodized salt in study area. Residence area, education level, household job, and average monthly income were significantly associated with knowledge of iodized salt at household level. Residence area, educational level, average monthly income, and expose to sunlight were significantly associated with availability of adequately iodized salt. In this finding, the knowledge and practices of iodized salt at household level in Jibat woreda, Ethiopia, were poor, and the availability of iodine in iodized salt was inadequate. This is associated to residence area, education level of household, and average monthly income. Therefore, any concerned body/institution should have to work in the above gabs of the knowledge, practice, and availability of iodized salt. | 10.1155/2021/5562390 |
pubmed_723_12833 | Long noncoding RNAs (lncRNAs) have emerged as essential regulators of skeletal myogenesis, but few myogenesis-associated lncRNAs have been identified and our understanding of their regulatory mechanisms remains limited, particularly in goat. Here, we identified a novel lncRNA, TCONS_00006810 (named lncR-125b), from our previous lncRNA sequencing data on fetal (45, 60, and 105 days of gestation, three biological replicates for each point) and postnatal (3 days after birth, n = 3) goat skeletal muscle, and found that it is highly expressed in skeletal muscle and gradually upregulated during skeletal muscle satellite cell (SMSC) differentiation in goat. Notably, overexpression of lncR-125b accelerated the expression of myogenic differentiation 1 (MyoD 1) and myogenin (MyoG), and the formation of myotubes, and knockdown of lncR-125b showed opposite effects in SMSCs. Results of dual-luciferase assay and quantitative real-time polymerase chain reaction revealed that lncR-125b acts as a molecular sponge for miR-125b and that insulin-like growth factor 2 (IGF2), a critical regulator of skeletal myogenesis, is a direct target gene of miR-125b. Further analyses showed that lncR-125b negatively regulates miR-125b expression and positively regulates IGF2 expression in SMSCs. Mechanistically, lncR-125b promotes SMSC differentiation by functioning as a competing endogenous RNA (ceRNA) for miR-125b to control IGF2 expression. These findings identify lncR-125b as a novel noncoding regulator of muscle cell differentiation and skeletal muscle development in goat. | 10.3389/fgene.2019.01171 |
pubmed_162_9081 | Comprehending the decomposition process is crucial for our understanding of the mechanisms of carbon (C) sequestration in soils. The decomposition of plant biomass has been extensively studied. It revealed that extrinsic biomass properties that restrict its access to decomposers influence decomposition more than intrinsic ones that are only related to its chemical structure. Fungal biomass has been much less investigated, even though it contributes to a large extent to soil organic matter, and is characterized by specific biochemical properties. In this study, we investigated the extent to which decomposition of heathland fungal biomass was affected by its hydrophobicity (extrinsic property) and melanin content (intrinsic property). We hypothesized that, as for plant biomass, hydrophobicity would have a greater impact on decomposition than melanin content. Mineralization was determined as the mineralization of soil organic carbon (SOC) into CO2 by headspace GC/MS after inoculation by a heathland soil microbial community. Results show that decomposition was not affected by hydrophobicity, but was negatively correlated with melanin content. We argue that it may indicate that either melanin content is both an intrinsic and extrinsic property, or that some soil decomposers evolved the ability to use surfactants to access to hydrophobic biomass. In the latter case, biomass hydrophobicity should not be considered as a crucial extrinsic factor. We also explored the ecology of decomposition, melanin content, and hydrophobicity, among heathland soil fungal guilds. Ascomycete black yeasts had the highest melanin content, and hyaline Basidiomycete yeasts the lowest. Hydrophobicity was an all-or-nothing trait, with most isolates being hydrophobic. | 10.1007/s00248-018-1167-3 |
pubmed_394_19717 | The myogenic basic helix-loop-helix regulatory factors (MRFs) maintain commitment of proliferating cells to the skeletal myogenic lineage, and contribute to activation of transcription of muscle-specific genes in myocytes and muscle fibers. A clear role for any or all of the MRFs in muscle fiber-type determination, however, has not emerged from expression or genetic studies. During fetal, neonatal and adult life, diversification of muscle fiber types, and the dynamics of slow or fast fiber type adaptation and growth, are controlled by exogenous factors, including innervation, work load, and hormonal signaling. In contrast, stereotypical development of muscle fibers preferentially expressing slow or fast isoforms of sarcomeric proteins in the embryo occurs in the absence of these factors, and appears to be mediated both by input from the surrounding interstitial milieu, as well by cell autonomous mechanisms. We report here that diversification of myogenic cells in culture towards the expression of fast or slow skeletal muscle fiber types can be determined by the activity and dose of at least one MRF, myogenin. The dose of myogenin is modulated by two parameters: the phosphorylation state of the transcriptional activation domains, and the level of expression. Low doses of myogenin promoted a fast phenotype, whereas higher doses promoted a slow phenotype, and further studies suggested that diversification is mediated by both transcriptional and post-transcriptional mechanisms. The potential for dose or numeration signaling by basic helix-loop-helix regulators has been revealed by studies in Drosophila melanogaster, while the present results support the notion that this mechanism may be more commonly employed to generate subdiversity among developing cell types. | 10.1016/j.cellsig.2008.09.020 |
pubmed_574_21852 | The effects of human recombinant basic fibroblastic growth factor (bFGF) on the secretion and/or proliferation of 26 human anterior pituitary adenomas secreting PRL alone (6 tumors), PRL and GH (18 tumors), or GH alone (2 tumors) were examined. Secretory studies were performed over 4 h, 4 days, and 21 days, and proliferation studies over 4 days. The acute effect of bFGF on secretion over 4 h was examined in 10 tumors. bFGF (10 nmol/L) increased PRL compared to that in controls (100%) in 2 tumors (126% and 290%; P < 0.05) and PRL and GH in a third tumor (183% and 133%, respectively; P < 0.05), whereas 7 tumors remained unaffected. Fourteen tumors were studied over 4 days. bFGF (10 nmol/L) increased PRL secretion in 9 of 11 tumors (117-525%; P < 0.05) cosecreting PRL and GH and in all 3 tumors secreting PRL alone (156%, 183%, and 691%; P < 0.01). Dose-response curves with 0.1, 1, and 10 nmol/L bFGF in 2 of these tumors cosecreting GH and PRL showed that stimulation was achieved with all 3 concentrations. bFGF (10 nmol/L) stimulated GH secretion in 2 of 11 mixed tumors (159% and 196%, respectively; P < 0.05). In 2 tumors studied over 3 weeks, 5 nmol/L bFGF stimulated PRL secretion progressively without affecting GH secretion (106% and 207%; P < 0.05). Tissue proliferation was determined by double immunostaining after bromodeoxyuridine incorporation for 1 h in 7 tumors after 4 days. The labeling index did not exceed 1.2% in any tumor, and there was no effect of 10 nmol/L bFGF on the proliferation of adenoma cells. These results suggest that bFGF may have a paracrine role in the stimulatory regulation of PRL secretion in human pituitary adenomas, and these effects are most likely due to increased hormonal synthesis. An in vitro cell culture system can be used to study proliferative potential. However, bFGF is not mitogenic for human anterior pituitary adenomas secreting PRL and PRL plus GH in vitro. | 10.1210/jcem.77.3.8370706 |
others_46_511 | The study investigated the developmental changes of Myoglobin (MB) in muscles of Jinhua pig (China's fatty breed) and the breed differences between Jinhua and Landrace (lean) pigs. About 30 Jinhua and Landrace barrows (three of each breed, at birth, age 60, 90, 120 and 150 days) were used to detect the postnatal growth changes of MB, peroxisome proliferator-activated receptor gamma, co-activator 1 alpha (PPARGC1A) and Peroxisome Proliferator-Activated Receptor Delta (PPARD) mRNA expression and soluble MB concentration (SM) in M. Longissimus Dorsi muscle (LD). Results showed that MB and PPARD mRNA expression in LD were significantly affected by ages of pig andPPARGClAmRNA expression in LD was lower at birth and significantly higher from age 60-150 days (p<0.05). The differences of MB, PPARGC1A and PPARD mRNA expression and SM in LD between two pig breeds were also investigated. The data showed that MB and PPARD mRNA expression and SM in LD of Jinhua barrows were significantly higher (p<0.05) than that of Landrace barrows from 60-150 days but no significant difference at birth and PPARGC1A mRNA expression were similar but the age was only at 120 days (p<0.01). At last, MB, PPARGC1A and PPARD mRNA expression and the correlation among gene, protein, CIE (a uniform colorimetric system defined by the Commission Internationale de l'Eclairage) and pH were evaluated. The data showed that the correlation between MB, SM, PPARGC1A and PPARD mRNA expression in LD were high and the correlation coefficients between MB and SM, PPARGC1A, PPARD, CIE L* and CIE a*-values were 0.81, 0.44, 0.81, -0.26 and 0.69, respectively. Correspondingly, the correlations between SM andPPARGCl A, PPARD, CIE L*, CIE a* were 0.44, 0.74, -0.26 and 0.73, respectively. In summary, the study is the first one which was conducted to explain the postnatal growth changes of MB mRNA expression in skeletal muscles of Jinhua pigs and provides information for development of nutritional methods to regulate MB in regulating and improving meat quality. © Medwell Journals, 2011 | 10.3923/javaa.2011.2493.2498 |
pubmed_106_11132 | The association between psychotic symptoms and violence is unclear, due in part to methodological features of investigations that have examined this question, and in part to the fact that the association likely differs by disorder and treatment conditions. Using data from The Comparative Study of the Prevention of Crime and Violence by Mentally Ill Persons, we examined 128 men with schizophrenia or schizoaffective disorder discharged from general and forensic psychiatric hospitals in Canada, Finland, Germany, and Sweden. The association between symptoms and aggressive behavior was studied during two 6 month periods when the patients lived in the community. Severe positive and negative symptoms of psychosis, depression, and anxiety were measured at the beginning of each of the 6 month periods. In addition, at the beginning of the second 6 month period changes in symptoms in the previous period were indexed. Aggressive behavior was measured in each 6 month period by reports from patients and from collaterals. During the first 6 months post-discharge, after controlling for the presence of antisocial personality disorder or PCL score and past diagnoses of alcohol/drug abuse/dependence, the presence of a severe positive symptom significantly increased the risk of aggressive behavior. During the second 6 month period, after controlling for antisocial personality disorder or PCL score and self-reported alcohol/drug use, the presence of a severe positive symptom, a TCO symptom, and an increase in TCO symptoms significantly increased the risk of aggressive behavior. Neither depot medications nor obligatory community treatment reduced the risk of aggressive behavior after controlling for the presence of a severe positive symptom and/or TCO symptoms. These findings suggest that, among men with schizophrenia being treated in the community, the presence of severe psychotic symptoms and the development of TCO symptoms are antecedents of aggressive behavior. | 10.1002/bsl.540 |
pubmed_599_9584 | BACKGROUND
The disease burden caused by recently identified respiratory viruses like HCoV-NL63 is unknown.
OBJECTIVES
We determined the burden of disease due to HCoV-NL63 infections using the population-based PRI.DE cohort of children under the age of 3 with lower respiratory tract infections (LRTIs).
STUDY DESIGN
In total 1756 respiratory samples, from hospitalized children or children who visited the outpatient clinic, were tested for HCoV-NL63. Sampling covered a period of 2 years and the frequency of infection in different years was compared to other Western European studies that tested for this virus in 2 or more consecutive years.
RESULTS
Sixty-nine samples were HCoV-NL63 positive, 35 were with high loads, and of these 25 were single HCoV-NL63 infections. Based on the number of children with high HCoV-NL63 infection and no additional infection, the overall annual incidence in outpatients was 7 per 1000 children per year (95% confidence interval (CI) 3-13 per 1000 children per year), which can be extrapolated to an absolute number of 16,929 visits to the physician due to an HCoV-NL63 infection in Germany per year. The estimated hospitalization rate is 22 per 100,000 children (95% CI: 7-49 per 100,000 children per year). This number reflects 522 HCoV-NL63 children in Germany per year. A large year-to-year difference in HCoV-NL63 infection frequency was observed. Combining these data with those of other studies in Western Europe revealed that HCoV-NL63 infections follow a 2-year inter-epidemic period with peaks of infection in the winters of 2000/2001, 2002/2003 and 2004/2005 (p<0.0001).
CONCLUSIONS
HCoV-NL63 infection in children below 3 years of age often requires a visit to the physician in an outpatient clinic, especially during peak-years, but hospitalizations are relatively infrequent. | 10.1016/j.jcv.2010.02.023 |
pubmed_1092_24606 | The purpose of this report is to describe our experience with the implementation of a practice quality improvement (PQI) project in thoracic imaging as part of the American Board of Radiology Maintenance of Certification process. The goal of this PQI project was to reduce the effective radiation dose of routine chest CT imaging in a busy clinical practice by employing the iDose(4) (Philips Healthcare) iterative reconstruction technique. The dose reduction strategy was implemented in a stepwise process on a single 64-slice CT scanner with a volume of 1141 chest CT scans during the year. In the first annual quarter, a baseline effective dose was established using the standard filtered back projection (FBP) algorithm protocol and standard parameters such as kVp and mAs. The iDose(4) technique was then applied in the second and third annual quarters while keeping all other parameters unchanged. In the fourth quarter, a reduction in kVp was also implemented. Throughout the process, the images were continually evaluated to assure that the image quality was comparable to the standard protocol from multiple other scanners. Utilizing a stepwise approach, the effective radiation dose was reduced by 23.62 and 43.63 % in quarters two and four, respectively, compared to our initial standard protocol with no perceived difference in diagnostic quality. This practice quality improvement project demonstrated a significant reduction in the effective radiation dose of thoracic CT scans in a busy clinical practice. | 10.1007/s10278-016-9877-x |
pubmed_893_7810 | Purpose
To investigate whether benzo(e)pyrene (B(e)P), a toxicant in cigarette smoke, affects the endothelium-dependent nitric oxide (NO)-induced vasodilation of the retinal arterioles, and whether oxidative stress, distinct protein kinase signaling pathways, and endoplasmic reticulum (ER) stress are associated with the B(e)P-induced effect on the retinal arterioles.
Methods
In this in vitro study, porcine retinal arterioles were isolated, cannulated, and pressurized without flow. These vessels were treated with intraluminal administration of B(e)P or B(e)P plus blockers for 180 minutes. Diametric changes to agonists were recorded by videomicroscopy.
Results
Intraluminal treatment with 100 μM B(e)P for 180 minutes significantly reduced the arteriolar vasodilation caused by the endothelium-dependent NO-mediated agonists bradykinin and A23187 but not that caused by endothelium-independent NO donor sodium nitroprusside. The adverse effects of B(e)P on the vasodilatory action of bradykinin were prevented by the superoxide scavenger 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPOL), the nicotinamide adenine dinucleotide phosphate-oxidase (NADPH oxidase) inhibitor apocynin, the c-Jun N-terminal kinase (JNK) inhibitor SP600125, the p38 mitogen-activated protein kinase inhibitor SB203580, genistein, resveratrol (RSV), and the ER stress inhibitor 4-phenylbutyrate (4-PBA). The xanthine oxidase inhibitor allopurinol did not alter the effect of B(e)P on the vasodilatory action induced by bradykinin.
Conclusions
B(e)P decreases the endothelium-dependent NO-induced vasodilation in the retinal arterioles through the production of superoxide from NADPH oxidase, which is linked to JNK and p38 kinase. The results suggested that ER stress is instrumental in B(e)P-induced endothelial dysfunction and that genistein and RSV might preserve endothelial function. | 10.1167/iovs.17-21925 |
pubmed_128_22866 | Physiological loads that act on the femoropopliteal artery, in combination with stenting, can lead to uncharacteristic deformations of the stented vessel. The overall goal of this study was to investigate the effect of stent length and stent location on the deformation characteristics of the superficial femoral artery (SFA) using an anatomically accurate, three-dimensional finite element model of the leg. For a range of different stent lengths and locations, the deformation characteristics (length change, curvature change, and axial twist) that result from physiological loading of the SFA along with the mechanical behavior of the vessel tissue are investigated. Results showed that stenting portions of the SFA leads to a change in global deformation characteristics of the vessel. Increased stress and strain values and altered deformation characteristics were observed in the various stented cases of this study, which are compared to previous results of an unstented vessel. The study concludes that shortening, twist and curvature characteristics of the stented vessel are dependent on stent length and stent location within the vessel. | 10.1115/1.4027329 |
others_239_15228 | The bursae suspensions at different hours post - infection were subjected to AGPT, dot-EL SA and RT-PCR to compare their sensitivity in detecting the presence of IBD virus in the early stage of infection. Until 36 hr post - infection, the antigen could not be detected by AGPT and dot-ELISA, whereas it was possible to detect viral RNA by RT-PCR at 24 hr post - infection. Hence, RT-PCR was highly sensitive in detecting the virus during early stage of IBDV inf | others_239_15228 |
others_304_6092 | The spider Latrodectus hesperus Chamberlin & Ivie (Araneae: Theridiidae) was subjected to low and ultralow oxygen (ULO) treatments at different temperatures. Complete control of the spiders was achieved in 24-h ULO treatments with 0.5% O2 or lower at 1°C and in a 24-h low oxygen (2%) treatment at 15°C. Oxygen level and temperature greatly affected spider mortality. At 1°C, as oxygen level was decreased from 2 to 0.5%, spider mortality increased from 0 to 100%. At 2% O2, as temperature was increased from 1 to 15°C, spider mortality increased from 0 to 100%. Grape clusters from two table grape (Vitis spp.) cultivars, 'Thompson Seedless' and 'Flame Seedless', were subjected to the 24-h ULO treatment with 0.5% O 2 at 1°C. The ULO treatment had no negative effects on grape quality. Because of the relatively short treatment time, effectiveness at low storage temperature and the easily attained oxygen level, we conclude that the ULO treatment have good potential to be implemented commercially for control of black widow spiders on harvested table grapes | 10.1603/0022-0493(2008)101[1515:UOTFCO]2.0.CO;2 |
pubmed_459_11036 | Polyclonal antibodies against osteonectin, a 32 kd non-collagenous bone protein, were applied for the histogenetic identification of variously differentiated osteosarcoma tissues. A strong positive reaction was found in matrix-producing osteosarcoma cells of the osteoblastic type, but pleomorphic or fibrosarcomatous osteosarcoma tissues reacted focally positive as well. Because the production of osteonectin depends on the osteoblastlike function of the individual tumor cell, a homogeneous immunocytochemical staining of all tumor cells cannot be expected. Nevertheless, the immunocytochemical demonstration of osteonectin in osteolytic tumors that produce no or scarcely any matrix seems to be a valuable tool for establishment of their osteogenic origin. | pubmed_459_11036 |
pubmed_1050_15531 | Cardiovascular disease is a serious threat to human health and a leading cause of mortality worldwide. Recent years have witnessed exciting progress in the understanding of heart formation and development, enabling cardiac biologists to make significant advance in the field of therapeutic heart regeneration. Most of our understanding of heart development and regeneration, including the genes and signaling pathways, are driven by pioneering works in non-mammalian model organisms, such as fruit fly, fish, frog, and chicken. Compared to mammalian animal models, non-mammalian model organisms have special advantages in high-throughput applications such as disease modeling, drug discovery, and cardiotoxicity screening. Genetically engineered animals of cardiovascular diseases provide valuable tools to investigate the molecular and cellular mechanisms of pathogenesis and to evaluate therapeutic strategies. A large number of congenital heart diseases (CHDs) non-mammalian models have been established and tested for the genes and signaling pathways involved in the diseases. Here, we reviewed the mechanisms of heart development and regeneration revealed by these models, highlighting the advantages of non-mammalian models as tools for cardiac research. The knowledge from these animal models will facilitate therapeutic discoveries and ultimately serve to accelerate translational medicine. | 10.3389/fcell.2020.595488 |
pubmed_974_15121 | Stroke represents one of the major causes of disability and mortality worldwide and prediction of outcome represents a challenge for both clinicians and researchers. In the past years, many blood markers have been associated with stroke outcome but despite this evidence, no biomarker is routinely used in stroke management. In this review, we focus on markers of the neuroendocrine system, which represent potential candidates to be implemented in clinical practice. Moreover, we present a systematic review and literature-based meta-analysis for copeptin, a new biomarker of the hypothalamo-pituitary-adrenal axis that has shown additional predictive value over clinical information in a large prospective study. The meta-analysis of the included 7 studies, with more than 2000 patients, reinforced its association with poor outcome (pooled odds ratio: 2.474 [1.678-3.268]) and mortality (pooled OR: 2.569 [1.642-3.495]). We further review the current situation of the topic and next steps to implement these tools by clinicians. | 10.1586/14737175.2014.977867 |
pubmed_862_14201 | Three studies look at whether the assumption of causal determinism (the assumption that all else being equal, causes generate effects deterministically) affects children's imitation of modeled actions. These studies show even when the frequency of an effect is matched, both preschoolers (N = 60; M = 56 months) and toddlers (N = 48; M = 18 months) imitate actions more faithfully when modeled actions are deterministically rather than probabilistically effective. A third study suggests that preschoolers' (N = 32; M = 58 months) imitation is affected not just by whether the agent's goal is satisfied but also by whether the action is a reliable means to the goal. Children's tendency to generate variable responses to probabilistically effective modeled actions could support causal learning. | 10.1111/j.1467-8624.2007.01132.x |
pubmed_532_13666 | A 3-dimensional model based on a molecular structural recipe having some unique and unexpected shape characteristics is demonstrated. The project was originally initiated to satisfy the aesthetic creative impulse to build a 3-dimensional model or sculpture. Further scientific investigation explained some important nanoscale structural observations that had been seen many years beforehand and mistakenly explained. This is a rare example of artistic creativity resulting in a key scientific advance. | pubmed_532_13666 |
pubmed_840_20003 | Benign acute myositis associated with influenza is reported from all over the world. The characteristics of this disorder is calf pain and difficulty walking during a viral illness (3-8 days) and creatine kinase levels are mildly or moderately elevated. Recovery occurred within 1 week. Midchildhood (mean age: 6-8 years) is most commonly affected and boys are more commonly than girls and its ratio is 2.4 : 1 by Shimizu in Japan (1993). Elderly patients are also reported. Viral studies show that influenza B is more commonly than influenza A and the ratio is 6 : 1 by Hu in Taiwan (2004), 2.4 : 1 by Shimizu in Japan (1993). Muscle histology revealed isolated segmental muscle degeneration and necrosis without frank myositis. A direct role of influenza virus in its genesis is not clear. An age-related response and occurrence primarily on boys may reflect a genetic predisposition. | pubmed_840_20003 |
pubmed_397_16039 | Difficulties in characterization of spermatozoa of the Metazoa are now related to insufficiency of the traditional terms "primitive spermatozoon", "modified spermatozoon", and "aberrant spermatozoon" introduced by G. Retzius and A. Franzen for description of intermediate forms discovered in the 20th century. In this respect, some authors propose to reject the Retzius' and Franzen's terms and turn to the terminological system of D. Rouse and B. Jamieson, the terms of which ("ectaquaspermatosoa", "entaquaspermatozoa", and "introspermatozoa") determine specific features of insemination, but do not reflect the structure of spermatozoa. The assertion of "helplessness" of the traditional structural Retzius' and Franzen's terms is unfounded. Their preservation is desirable if one wishes to preserve the comparative-morphological approach to the characterization of male gametes of the Metazoa. The terms "primitive spermatozoon", "modified spermatozoon", and "aberrant spermatozoon" will become more universal if the method of their combined utilization is applied. | pubmed_397_16039 |
pubmed_550_21468 | A chronically weak area in research papers, reports, and reviews is the complete identification of seminal background documents that formed the building blocks for these papers. A method for systematically determining these seminal references is presented. Citation-Assisted Background (CAB) is based on the assumption that seminal documents tend to be highly cited. Application of CAB to the field of Anthrax research is presented. While CAB is a highly systematic approach for identifying seminal references, it is not a substitute for the judgment of the researchers, and serves as a supplement. | 10.1080/10408410701451930 |
pubmed_1090_18449 | The genetically caused intensity of growth from piglets (barrows) of four breeds and two crossbreeds was evaluated by estimation of maximum daily capacity per LW 0.67 kg of N-balance plus N-maintenance-requirement (A) on the basis of a total of 130 N balance measurings on 66 piglets in the live weight range between 10 and 20 kg. The estimation was realized by using the N utilization model by Gebhardt (1963) and of its further development. In comparison with Landrace (A = 2575 mg) the breeds Edelschwein (A = 3,242 mg) and Leicoma (A = 3,038 mg) had a higher A in the midst of the piglet period (9th and 10th week of life), but not so the breed Schwerfurter (A = 2,350 mg). The capacity of the following N balances during growing and fattening stages is not derivable from these values. The experimentally evaluated A of crossbreeds is in good agreement with the calculated A on the basis of the used races for breeding. The product A.b = 1.15 is characterizing the quality of the feed protein (a mixture of wheat and casein in the relation 2.2:1), independently of the live weight and also of the breed or the genotype of the pig. | 10.1080/17450399009421090 |
pubmed_403_13213 | Data sources Cochrane Central Register of Controlled Trials (CENTRAL), Medline (Ovid), Embase, Web of Science, Latin American & Caribbean Health Sciences Literature (LILACS) and SIGLE database.Study selection Randomised controlled trials (RCTs), controlled clinical trials (CCTs), cohort studies, case-control studies and cross-sectional studies.Data extraction and synthesis Two reviewers screened papers independently and assessed the risk of bias. Data categorised based on the study design. The primary outcome was the odds ratio (OR)/relative risk (RR) and confidence interval (CI) for hypertension in individuals with periodontitis.Results Diagnoses of moderate-to-severe (OR = 1.22; 95% CI: 1.10-1.35) and severe periodontitis (OR = 1.49; 95% CI: 1.09-2.05) were associated with hypertension. Diagnosis of periodontitis increased odds of occurring hypertension (OR = 1.68; 95% CI: 0.85-3.35). Patients with periodontitis exhibited higher mean systolic (weighted mean difference [WMD] of 4.49 mmHg; 95% CI: 2.88-6.11) and diastolic blood pressures (2.03 mmHg; 95% CI: 1.25-2.81). There was inconclusive evidence that periodontal therapy reduces blood pressure (3-12.5 mmHg of systolic and 0-10 mmHg of diastolic blood pressures).Conclusions Periodontitis could be associated with increased risk of hypertension. Further, the management of periodontitis could impact on the management of hypertension. However, there is still a need for more high-quality research. | 10.1038/s41432-020-0137-z |
pubmed_349_25786 | Physical activity is emerging from epidemiologic research as a lifestyle factor that may improve survival from colorectal, breast, and prostate cancers. However, there is considerably less evidence relating physical activity to cancer recurrence and the biologic mechanisms underlying this association remain unclear. Cancer patients are surviving longer than ever before, and fear of cancer recurrence is an important concern. Herein, we provide an overview of the current epidemiologic evidence relating physical activity to cancer recurrence. We review the biologic mechanisms most commonly researched in the context of physical activity and cancer outcomes, and, using the example of colorectal cancer, we explore hypothesized mechanisms through which physical activity might intervene in the colorectal recurrence pathway. Our review highlights the importance of considering pre-diagnosis and post-diagnosis activity, as well as cancer stage and timing of recurrence, in epidemiologic studies. In addition, more epidemiologic research is needed with cancer recurrence as a consistently defined outcome studied separately from survival. Future mechanistic research using randomized controlled trials, specifically those demonstrating the exercise responsiveness of hypothesized mechanisms in early stages of carcinogenesis, are needed to inform recommendations about when to exercise and to anticipate additive or synergistic effects with other preventive behaviors or treatments. | 10.1007/s00109-017-1558-9 |
pubmed_466_10253 | The extracellular matrix of heart muscle contains a considerable variety of structures. We have systematically studied the morphology of these structures using several methods of fixation and microscopy. Endomysial connections between cells are comprised of struts of collagen [1] as well as combinations of elastin fibers, collagen fibers, and microfibrils. The rest of the extracellular matrix is filled with a polyanionic lattice of unit collagen fibrils, microthreads, and granules. In the course of these investigations, we have observed regions of structural continuity across the sarcolemma, from endomysial collagen struts to Z-bands. We have also correlated the mechanical resistance to stretch with orientation of epimysial collagen fibers and sarcomere lengths in living as well as fixed rat papillary muscles. Our observations suggest that the extracellular skeletal framework plays an important role in normal cardiac function. | 10.1007/978-1-4757-1287-2_19 |
pubmed_1070_20488 | In Heliconius butterflies, it has been proposed that speciation occurs through a combination of divergence in ecological habitat preferences and mimetic colour patterns. Here we test this hypothesis by investigating a parapatric form of the widespread species Heliconius erato. Mendelian (colour patterns) and molecular genetic data permit us to address hypotheses about introgression and genetic differentiation between different populations. Combined analysis of colour pattern, microsatellite loci and mitochondrial DNA showed that Heliconius erato venus and Heliconius erato chestertonii form a bimodal hybrid zone implying partial reproductive isolation. In a sample of 121 individuals collected in sympatry, 25% were hybrids representing a significant deficit of heterozygotes compared to the Hardy-Weinberg expectation. Seven microsatellite loci, analysed for a subset of these individuals, showed marked differentiation between the parental taxa, and unambiguously identified two genotypic clusters concordant with our phenotypic classification of individuals. Mitochondrial DNA analysis showed H. erato venus as a monophyletic group well differentiated from H. erato chestertonii, implying a lack of historical introgression between the populations. Heliconius erato chestertonii is therefore an incipient species that maintains its integrity despite high levels of hybridization. Moreover, H. erato chestertonii is found at higher altitudes than other races of H. erato and has a distinct colour pattern and mimetic relationship. Hence, there are now two examples of parapatric incipient species related to H. erato, H. himera and H. erato chestertonii, both of which are associated with higher altitudes, more arid habitats and distinct mimetic relationships. This implies that parapatric habitat adaptation is a likely cause of speciation in this group. | 10.1111/j.1365-294X.2008.03934.x |
pubmed_989_2333 | BACKGROUND
Despite its benefits, a major concern regarding antipsychotic treatment is its possible impact on the brain's structure and function. This study sought to explore the characteristics of white matter structural networks in chronic never-treated schizophrenia and those treated with clozapine or risperidone, and its potential association with cognitive function.
METHODS
Diffusion tensor imaging was performed on a unique sample of 34 schizophrenia patients treated with antipsychotic monotherapy for over 5 years (17 treated with clozapine and 17 treated with risperidone), 17 never-treated schizophrenia patients with illness duration over 5 years, and 27 healthy control participants. Graph theory and network-based statistic approaches were employed.
RESULTS
We observed a disrupted organization of white matter structural networks as well as decreased nodal and connectivity characteristics across the schizophrenia groups, mainly involving thalamus, prefrontal, and occipital regions. Alterations in nodal and connectivity characteristics were relatively milder in risperidone-treated patients than clozapine-treated patients and never-treated patients. Altered global network measures were significantly associated with cognitive performance levels. Structural connectivity as reflected by network-based statistic mediated the difference in cognitive performance levels between clozapine-treated and risperidone-treated patients.
LIMITATIONS
These results are constrained by the lack of random assignment to different types of antipsychotic treatment.
CONCLUSION
These findings provide insight into the white matter structural network deficits in patients with chronic schizophrenia, either being treated or untreated, and suggest white matter structural networks supporting cognitive function may benefit from antipsychotic treatment, especially in those treated with risperidone. | 10.1093/ijnp/pyaa061 |
pubmed_130_676 | INTRODUCTION
Glucose absorption during peritoneal dialysis (PD) is commonly assumed to occur via paracellular pathways. We recently showed that SGLT2 inhibition did not reduce glucose absorption in experimental PD, but the potential role of glucose transport into cells is still unclear. Here we sought to elucidate the effects of phlorizin, a non-selective competitive inhibitor of sodium glucose co-transporters 1 and 2 (SGLT1 and SGLT2), in an experimental rat model of PD.
METHODS
A 120-min PD dwell was performed in 12 anesthetised Sprague-Dawley rats using 1.5% glucose fluid with a fill volume of 20 mL with (n = 6) or without (n = 6) intraperitoneal phlorizin (50 mg/L). Several parameters for peritoneal water and solute transport were monitored during the treatment.
RESULTS
Phlorizin markedly increased the urinary excretion of glucose, lowered plasma glucose and increased plasma creatinine after PD. Median glucose diffusion capacity at 60 min was significantly lower (p < 0.05) being 196 µL/min (IQR 178-213) for phlorizin-treated animals compared to 238 µL/min (IQR 233-268) in controls. Median fractional dialysate glucose concentration at 60 min (D/D 0) was significantly higher (p < 0.05) in phlorizin-treated animals being 0.65 (IQR 0.63-0.67) compared to 0.61 (IQR 0.60-0.62) in controls. At 120 min, there was no difference in solute or water transport across the peritoneal membrane.
CONCLUSION
Our findings indicate that a part of glucose absorption during the initial part of the dwell occurs via transport into peritoneal cells. | 10.1177/08968608221080170 |
pubmed_613_24198 | The physiological responses of plants to elevated CO(2) have not been incorporated into most models of ecosystem function under changed climate. These responses are now well documented, and recent work demonstrates that they can be readily included in ecosystem models. Simulations show that the effects of elevated CO(2) levels on transpiration and gas exchange will increase the sensitivity of community structure (particularly of forests) to climate change. | 10.1016/0169-5347(90)90087-T |
pubmed_653_7259 | Permanent changes occurring in economy and politics, open borders, a greater number of people with higher education as well as growing social awareness concerning taking care of health are followed by changes in healthcare sector. In response to an increased social demand, new medical institutions are being founded. They offer their patients a vast array of services ranging from therapeutic to preventive and highly specialized procedures improving their standard of living. In order to attract regular patients, and therefore receive regular income, it is necessary to stabilize such institutions on services market. It can be achieved by numerous marketing tools which, when applied appropriately, enable to create a positive image of a medical institution. | pubmed_653_7259 |
pubmed_459_4191 | Twelve neonates with hypertension have been followed for a mean of 5.75 years. At onset of hypertension, mean peak blood pressure was 159/99 mm Hg. Ten infants had umbilical artery catheters, 9 placed above the origin of the renal arteries. Radionuclide renal scan and/or angiography demonstrated renovascular disease, primarily renal artery thrombosis, in 11 infants. One-third of infants were asymptomatic, one-third had normal urinalyses and two-thirds had elevated peripheral plasma renin activities. Blood pressure normalized with medical therapy in all infants and remained normal when therapy was discontinued. Ten infants have normal creatinine clearances on follow-up but 5/11 have unilateral renal atrophy. Radionuclide scans have remained abnormal, even in infants without renal atrophy. In summary, neonatal renovascular hypertension is frequently secondary to renal artery thrombosis, associated with umbilical artery catheterization. Blood pressure usually normalizes with conservative medical management and remains normal off medications. Persistent abnormalities in renal size and function are common. | 10.1007/BF00866882 |
pubmed_808_11780 | Functional lateralization is highly replicable trait of human neural system. Many previous studies have indicated the possibility that people with attention-deficits/hyperactivity-disorder (ADHD) and autism spectrum disorder (ASD) show hemispheric asymmetry in atypical neural function. However, despite the abundance of relevant studies, there is still ongoing controversy over this issue. In the present mini-review, we provide an overview of the hemispheric asymmetry in atypical neural function observed in fNIRS studies on people with these conditions. Atypical neural function is defined as group-difference in the task-related concentration change of oxygenated hemoglobin. The existing fNIRS studies give support to the right-lateralized atypicalty in children with ADHD. At the same time, we did not find clear leftward-lateralization in atypical activation in people with ASD. On the basis of these, we discuss the current states and limitation of the existing studies. | 10.3389/fnhum.2017.00137 |
pubmed_133_2836 | OBJECTIVES
Dendritic cells (DC) are potential first target cells in sexually transmitted HIV-1 infection. They are also considered to be central in the activation of naive T cells, which thereupon can become permissive for HIV-1. In addition, activated DC express effector molecules, which likely contribute to the direction of T helper (Th1/Th2)-specific immune responses.
METHODS
The capacity of cytokine and chemokine production in in vitro DC infected and uninfected with HIV-1 was assessed by enzyme-linked immunosorbent assay (ELISA) and by in situ immunocytochemical detection at the single cell level. Fluorescent in situ 5'-nuclease assay (FISNA) was used for quantitative evaluation of HIV-1 gag-positive cells.
RESULTS
Macrophage-tropic HIV-1 effectively infected 20-40% of in vitro cultured DC. However, this activity alone did not induce detectable cytokine or chemokine protein expression in DC. In contrast, lipopolysaccharide (LPS) stimulation of these HIV-1-infected DC resulted in a significantly increased level of cells producing tumour necrosis factor alpha (TNF-alpha) and interleukin (IL) 1beta but reduced frequencies of cells producing IL-1 receptor antagonist (IL-1ra) compared with the LPS-stimulated but uninfected DC cultures (P < 0.05). Furthermore, an extensive production of the beta-chemokines [RANTES, macrophage inflammatory proteins (MIP) 1alpha and 1beta] was detected in DC in response to both LPS and HIV-1 plus LPS.
CONCLUSIONS
These findings indicate that HIV-1 infected DC may have an increased proinflammatory activity. Elevated production of cytokines such as TNF-alpha and IL-1beta and reduced IL-1ra may contribute to enhanced replication of HIV-1 in bystander T cells. Gram-negative bacterial infection and gut-associated bacterial translocation in HIV-1-infected individuals may also result in endotoxin-mediated reactivation of HIV-1 in bystander CD4 CD45RO T cells caused by the increased production of proinflammatory cytokines in DC. | 10.1097/00002030-199910220-00003 |
pubmed_1134_12439 | OBJECTIVE
To determine the effect of acute (clinical history of glaucoma for <or= 2 days) and chronic (clinical history of glaucoma for 7 days) goniodysgenesis-related glaucoma on various stress-inducible proteins in canine retinas.
SAMPLE POPULATION
15 canine retinas (5 from control eyes, 5 from eyes with acute glaucoma, and 5 from eyes with chronic glaucoma).
PROCEDURES
Globes were obtained from the Comparative Ocular Pathology Laboratory of Wisconsin. Eyes were characterized on the basis of clinical history. The distribution of glial fibrillary acidic protein (GFAP), heat shock protein (HSP) 60, and hypoxia-inducible factor (HIF)-1alpha was determined by use of immunohistochemical analysis.
RESULTS
Intensity of GFAP staining increased with temporal progression of glaucoma. In specimens from eyes with acute glaucoma, staining for HSP 60 was more variable among eyes, compared with that of the control eyes, whereas specimens from eyes with chronic glaucoma typically had less HSP 60 staining than was evident in the control eyes. Neither the control eyes nor specimens from the eyes with acute glaucoma had nuclear staining for HIF-1alpha in the retinas. Four of 5 specimens from eyes with chronic glaucoma had nuclear staining for HIF-1alpha in cells of the outer nuclear layer. Staining for HIF-1alpha was distributed segmentally in regions of more severe atrophy and disorganization.
CONCLUSIONS AND CLINICAL RELEVANCE
Results of the study reported here supported a clinically evident, rapidly progressive disease with a shift in cell regulation between acute and chronic glaucoma and also supported ischemia as a mechanism of retinal injury in this disease. | 10.2460/ajvr.69.2.265 |
pubmed_282_12602 | The ascomycete Monilinia fructicola is the causal agent of brown rot of stone fruit in Brazil, causing major pre- and postharvest losses. For many years, the demethylation inhibitor (DMI) fungicide tebuconazole has been used as the most effective active ingredient for controlling brown rot and, as a result, strains of M. fructicola resistant to this ingredient have emerged in many Brazilian states producing stone fruit. The aim of this study was to investigate the mechanisms associated with the resistance of M. fructicola to DMI tebuconazole. By sequencing the M. fructicola CYP51 (MfCYP51) gene, encoding the azole target sterol 14α-demethylase, a mutation was identified at the nucleotide position 1,492, causing the amino acid substitution from glycine to serine at the codon position 461, associated with reduced tebuconazole sensitivity. In addition, it was observed that MfCYP51 gene expression could play a secondary role in DMI fungicide resistance of M. fructicola strains in Brazil. However, for the specific isolate found to exhibit elevated expression levels of MfCYP51, no insertions that would trigger gene expression were found. Based on the point mutation associated with tebuconazole resistance, an allele-specific polymerase chain reaction method was developed to quickly identify resistant genotypes within the Brazilian population. This is the first report determining molecular mechanisms for DMI resistance identification for M. fructicola isolates from Brazil. This information provides an important advancement for risk assessment of DMI fungicides used to manage brown rot of stone fruit. | 10.1094/PHYTO-02-17-0050-R |
pubmed_216_13614 | A 45-year-old female, who had undergone emergency drainage of a cyst, complained of severe dyspnea. Chest computed tomography scans showed a large mass, compressing the right pulmonary artery, superior vena cava, and tracheal bifurcation. Subtotal resection of the cyst wall was carried out due to dense adhesion to adjacent structures. Immediately after surgery, her symptoms resolved completely. Mediastinal bronchogenic cysts in the subcarinal space can cause severe respiratory distress from airway and vascular compression. | 10.1055/s-2006-924002 |
pubmed_661_7478 | The majority of the carboxy-terminal half of polyomavirus middle-T antigen has been variously mutated and, with the exception of the putative membrane-binding domain (amino acids 394 to 415), was found to be largely dispensible for the transforming activity of the protein. A comparison of the small-T antigen amino acid sequences (equivalent to the region of middle-T encoded by exon 1) of simian virus 40, BK virus, polyomavirus, and a recently described hamster papovavirus highlighted regions of potential interest in mapping functions to the amino-terminal half of polyomavirus middle-T antigen. The regions of interest include amino acids 168 to 191 (previously investigated by this group [S. H. Cheng, W. Markland, A. F. Markham, and A. E. Smith, EMBO J. 5:325-334, 1986]), two cysteine-rich clusters (amino acids 120 to 125 and 148 to 153), and amino acids 92 to 117 (within the limits of the previously described hr-t mutant, SD15). Point mutations, multiple point mutations, and deletions were made by site-specific and site-directed mutagenesis within the cysteine-rich clusters and residues 92 to 117. Studies of the transforming ability of the altered middle-T species demonstrated that this activity is highly sensitive to amino acid changes. All four regions (as defined above) within the amino-terminal half of middle-T have now been studied in detail. The phenotype of the mutants is predominantly transformation defective, and the corresponding variant middle-T species are characterized by being either totally or severely handicapped in the ability to associate actively with pp60c-src. Whether the mutations affect the regions of interaction between middle-T and pp60c-src or simply interfere with the overall conformation of this domain is not known. However, there would appear to be a conformational constraint on this portion of the molecule with regard to its interaction with pp60c-src and by extension to the ability of the middle-T species to transform. | 10.1128/JVI.61.2.285-292.1987 |
pubmed_1034_25324 | HINTERGRUND UND ZIELE
Die Behandlung schwerer dermatologischer Autoimmunerkrankungen und der toxischen epidermalen Nekrolyse (TEN) mit hochdosierten intravenösen Immunglobulinen (IVIg) ist ein bewährtes therapeutisches Verfahren in der Dermatologie. Da eine IVIg-Therapie in der Regel nur bei seltenen Erkrankungen oder bei schweren Fällen in Betracht gezogen wird, stützt sich die Anwendung von Immunglobulinen zumeist nicht auf Daten aus randomisierten kontrollierten Studien, wie sie in der evidenzbasierten Medizin erforderlich sind. Da Indikationen für die Anwendung von IVIg selten sind, ist es unwahrscheinlich, dass solche Studien in absehbarer Zeit durchgeführt werden. Wegen der hohen Kosten für IVIg im First-Line-Einsatz wurden die ersten klinischen Leitlinien für die Anwendung von IVIg bei dermatologischen Erkrankungen im Jahr 2008 herausgegeben und im Jahr 2011 überarbeitet.
METHODEN
Diese europäischen Leitlinien wurden von einer Gruppe durch das EDF und die EADV benannter Experten erarbeitet. Die Leitlinien wurden erstellt, um die derzeit als wirksam erachteten Behandlungsindikationen zu aktualisieren und die für die Anwendung von IVIg bei dermatologischen Autoimmunerkrankungen und TEN vorliegenden Daten zusammenzufassen.
ERGEBNISSE UND SCHLUSSFOLGERUNG
Die vorliegenden Leitlinien repräsentieren die einvernehmlichen Meinungen und Definitionen von Experten zur Anwendung von IVIg, die die aktuell publizierten Daten widerspiegeln, und sollen als Entscheidungshilfe für den Einsatz von IVIg bei dermatologischen Erkrankungen dienen. | 10.1111/ddg.13013_g |
pubmed_786_11065 | Carcinoma of the cervix is one of the leading malignancies in the developing countries including India. In view of this health care program might have to be redefined. Most of the data are available from the developed countries, which rely mainly on cytology screening on regular basis. This however may not be feasible in developing countries because of various constraints. Thus alternative approaches are needed based on risk reduction modalities. This article while dealing with the control approaches based on secondary prevention, reviews several risk factors associated with cervical cancer. The various articles were approached through Medline search including cross-references. The important life styles associated with cervical cancer and which are amenable to primary prevention strategies through health education, behavioral interventions, legislative approaches and modifying the health care seeking behavior were identified through the review process. These factors mainly pertain to early sexual debut, multiple sexual partners, menstrual hygiene and unprotected sex. Role of male partners has also been delineated in the process of cervical carcinogenesis. These factors are essentially conducive to the transmission of an etiological agent; the high-risk types human papillomaviruses, the more proximal cause in the web of causation. Barrier method of contraception and prophylactic vaccine in future could help to check the transmission of the virus. Role of smoking and oral contraceptives has also been discussed. Till the facilities for mass scale screening are developed in developing countries the primary prevention approaches could certainly help to check the incidence of the disease. | pubmed_786_11065 |
pubmed_139_880 | A total of 17 pediatric patients with pretreated acute lymphoblastic leukemia were included in a phase II study of idarubicin. Four of 16 complete remissions were obtained, confirming the activity of the drug in this indication. Toxicity was acceptable, though caution is needed in patients who have already received high cumulative doses of anthracyclines. | pubmed_139_880 |
pubmed_75_8712 | Norepinephrine turnover and concentrations were examined in eight brain regions of amygdala-kindled and yoked control rats. The subjects were killed 2 months after the kindled subjects had exhibited their sixth "stage 4-5" generalized seizure. No significant differences were found in norepinephrine turnover or concentrations between kindled and yoked control rats in any of the brain regions examined. Dopamine turnover and concentrations in brain regions were also unchanged in kindled rats compared with their yoked controls. The data suggest that amygdala kindling does not produce any long-lasting alterations in brain regional catecholamine turnover or concentrations. | 10.1016/0014-4886(86)90273-6 |
pubmed_337_19158 | PURPOSE
To test define characteristic fundus autofluorescence patterns of different exudative age-related macular degeneration subtypes.
METHODS
Cross-sectional study. Fifty-two patients with choroidal neovascularization because of three different neovascular age-related macular degeneration subtypes were included in the study. Macular and peripheral fundus autofluorescence patterns of study subjects were compared in a masked fashion.
RESULTS
Fundus autofluorescence patterns of all three neovascular age-related macular degeneration subtypes revealed similar patterns. However, peripapillary hypo-autofluorescence was more common among patients with polypoidal choroidal vasculopathy (88.2%) compared with patients with retinal angiomatous proliferation (12.5%) and patients without retinal angiomatous proliferation and polypoidal choroidal vasculopathy (21.1%) (P < 0.0001).
CONCLUSION
Presence of peripapillary fundus autofluorescence defects in neovascular age-related macular degeneration maybe suggestive of polypoidal choroidal vasculopathy as a variant of neovascular age-related macular degeneration. | 10.1097/IAE.0000000000001034 |
pubmed_1093_15796 | The current management of early rheumatoid arthritis (ERA) is to start an intensive treatment as soon as possible. To avoid under/overtreatment, it is important to identify reliable ERA evolution biomarkers. HLA-G molecules has been associated with rheumatoid arthritis, suggesting a role in disease regulation. HLA-G antigens are expressed as membrane bound and soluble isoforms (mHLA-G, sHLA-G) that act as ligand for immune-inhibitory receptors (ILT2, ILT4, KIR2DL4). Expression of HLA-G is influenced by a 14 bp insertion/deletion polymorphism in exon 8 of the gene, where the deletion is associated with mRNA stability. We analyzed 23 ERA patients during a 12 months follow-up disease treatment for sHLA-G, IL-1beta, IL-6, IL-10 and TNF-alpha levels in plasma samples by ELISA, mHLA-G and ILT2 expression on peripheral blood CD14 positive cells by flow cytometry and typed HLA-G 14 bp deletion/insertion polymorphism by Real-Time PCR. Disease status (DAS28), ultrasonography with power Doppler and laboratory data were checked. Cytokine levels confirmed the anti-inflammatory effect of the treatment. sHLA-G, mHLA-G and ILT2 expression inversely correlated with DAS28 disease scores. The frequency of 14 bp deletion allele increased in patients with disease remission. Based on these results, HLA-G may be a candidate biomarker to evaluate early prognosis and disease activity in ERA patients. | pubmed_1093_15796 |
pubmed_674_2934 | Transplants of white clover (Trifolium repens L.) were grown isolated from each other and in pairs placed at different distances apart. The paired plants developed asymmetrically and at the interface between paired clones both the density of nodes and of stolons appeared to reach ceiling values that were of the same order as those achieved in isolated clones. It is argued that the growth of plants of T. repens is controlled by the local conditions experienced by the plant parts and not by integrated growth of the whole. Transplants of three different genotypes of T. repens, which differed in growth form, were grown as neighbouring pairs and the calculated asymmetry of the plants was used to compare their mutual aggressivenes. The more compact (phalangeal) genotypes induced greater asymmetry in their neighbours than the more diffuse forms. | 10.1007/BF00377157 |
pubmed_906_13154 | The 26S proteasome plays a major role in eukaryotic protein breakdown, especially for ubiquitin-tagged proteins. Substrate specificity is conferred by the regulatory particle (RP), which can dissociate into stable lid and base subcomplexes. To help define the molecular organization of the RP, we tested all possible paired interactions among subunits from Saccharomyces cerevisiae by yeast two-hybrid analysis. Within the base, a Rpt4/5/3/6 interaction cluster was evident. Within the lid, a structural cluster formed around Rpn5/11/9/8. Interactions were detected among synonymous subunits (Csn4/5/7/6) from the evolutionarily related COP9 signalosome (CSN) from Arabidopsis, implying a similar quaternary arrangement. No paired interactions were detected between lid, base or core particle subcomplexes, suggesting that stable contacts between them require prior assembly. Mutational analysis defined the ATPase, coiled-coil, PCI and MPN domains as important for RP assembly. A single residue in the vWA domain of Rpn10 is essential for amino acid analog resistance, for degrading a ubiquitin fusion degradation substrate and for stabilizing lid-base association. Comprehensive subunit interaction maps for the 26S proteasome and CSN support the ancestral relationship of these two complexes. | 10.1093/emboj/20.24.7096 |
pubmed_358_20143 | Studies have shown that blocking B7-mediated costimulation induces T cell tolerance via anergy or apoptosis. Provision of exogenous IL-2 can reverse or prevent the induction of tolerance. We have previously shown that TCDD-induced suppression of the CTL response to allogeneic P815 tumor cells is accompanied by decreased expression of CD86 (B7-2) as well as suppressed IL-2 and IFNgamma production. In the present studies, the role of IL-2 and IFNgamma and the analysis of inappropriate deletion of CD8(+) cells was examined. Administration of IL-2 on days 7-9 relative to the injection of P815 tumor cells dose-dependently increased the CTL activity and the generation of CD8(+) CTL effector cells in TCDD-treated mice. This increased CTL response was not due to recruitment of naive CTL precursors (CTLp), suggesting that a small pool of activated CTLp in TCDD-treated mice could respond to the IL-2. A much larger pool of activated CTLp in control mice was also expanded by IL-2 treatment. In contrast, treatment with IFNgamma during the same time period did not alter CTL activity in control or TCDD-treated mice. To address the possibility that insufficient IL-2 early in the response was responsible for the reduced pool of activated CTLp in TCDD-treated mice, IL-2 was administered on days 1-3 after P815 injection. However, not only did early treatment with IL-2 fail to restore the response in TCDD-treated mice, it suppressed the CTL response of non-TCDD-treated mice. To test whether exposure to TCDD induced apoptosis of activated CD8(+) T cells, phosphatidylserine (PS) expression was measured on various days after P815 tumor challenge. Surprisingly, the percentage of apoptotic CD8(+) T cells was significantly lower in TCDD-treated mice compared to controls throughout the allograft response. Similarly, exposure to TCDD failed to enhance peripheral deletion of Vbeta3(+)CD8(+) T cells after injection of the superantigen Staphylococcal enterotoxin A (SEA). Taken together, the data indicate that TCDD induces an early defect in CTLp activation that is not due to insufficient IL-2 or deletion of CD8(+) cells and may implicate a novel mechanism by which ligands of the Ah receptor disrupt CTL precursor activation. | 10.1006/taap.2000.8971 |
pubmed_997_8990 | At the regional scale, substrate properties are the key factors driving litter decomposition rate. In this study, soil temperature was increased by buried heating cables to explore the impacts of climate warming on the physical and chemical properties in branch and leaf of Cunninghamia lanceolata litter. The results showed that after 5 years of soil warming (4 ℃), the contents of nitrogen (N), phosphorus (P) and water-soluble substance in branch litter increased by 35.2%, 40.8% and 7.6%, while that in leaf litter increased by 41.2%, 45.9% and 5.9%, respectively. The contents of carbon (C), cellulose and C/N in branch litter decreased by 5.1%, 11.6% and 28.8%, and in leaf litter decreased by 5.3%, 11.3% and 33.3%, respectively. Soil warming led to 29.8% increase in specific leaf area (SLA) and 40.7% decrease in tensile strength (LTS) of leaf litter. However, warming did not affect lignin content and pH value in both branch and leaf litter. 13C NMR and infrared spectrum analysis showed that the contents of amino acids, polysaccharides, polyphenols and aliphatic compounds in litter changed significantly after warming. Warming effect differed between litter organs, in that polysaccharides increased significantly only in leaf litter and the increase of amino acids in branch litter was greater than that in leaf litter. Overall, soil warming significantly changed the physical and chemical properties in C. lanceolata branch and leaf litter, which might accelerate the decomposition rate at the initial stage due to the increase of N, P contents and the decrease of LTS, but might decelerate the decomposition rate at the later stage due to an increase of complex polymers content in the litter. | 10.13287/j.1001-9332.202210.003 |
pubmed_824_9853 | Granulocyte-colony stimulating factor (G-CSF) is an endogenous growth factor that exhibits a diverse range of neuroprotective mechanisms against a variety of neurological disorders including ischemic stroke. We investigated the anti-apoptotic mechanisms of G-CSF against endoplasmic reticulum (ER) stress induced apoptosis. Sprague-Dawley rats were subjected to transient occlusion of the middle cerebral artery (MCAO) for 90 min. Rats were injected with G-CSF (n = 15; 50 μg/kg body weight s.c.) for 4 days, starting 24 h post-MCAO and brains were harvested after 4 days reperfusion (n = 16). Key proteins in ER stress apoptosis were analyzed by immunoblotting. G-CSF reduced infarct volume to 53% and improved neurological deficits. G-CSF treatment significantly (P < .05) attenuated the expression of proteins involved in ER stress apoptosis pathway; ATF4, ATF6, p-p38MAPK, pJNK and CHOP. G-CSF treatment also re-established ER homeostasis evident by the reduction of the intraluminal ER stress sensor, GRP78 as well as reducing the overall cellular stress level protein, HSP27. G-CSF also up-regulated anti-apoptotic proteins pAKT and Bcl-2 while down-regulated the pro-apoptotic protein Bax. G-CSF exerts neuroprotection from cerebral ischemia through the preservation of the ER, resulting in the attenuation of pro-apoptotic proteins and the potentiation of anti-apoptotic proteins. | 10.1016/j.brainres.2017.12.022 |
pubmed_388_6560 | An electrochemical detector for gas chromatographic analysis of hydrogen sulfide is described and its operating characteristics are discussed. The detector operation is based upon the measurement of the current when hydrogen sulfide is electrochemically oxidized at a diffusion electrode. The lower detectable limit was 3 X 10(-12) grams H2S, the precision was 0.5% and analysis was achieved within 2 minutes. Accuracy was limited principally by the preparation of calibration samples and the availability of standard reference gas mixtures. | 10.1093/chromsci/15.3.125 |
pubmed_572_9972 | Glioma is an aggressive primary Neuro-epithelial tumor with dismal prognosis, since there is a lack of molecular work-up during routine radiological monitoring of the disease. Currently, a number of potential molecular prognostic and predictive biomarkers are being characterized in line with structured diagnosis defined in World Health Organization guidelines 2016. Human-telomerase reverse-transcriptase (hTERT), a marker of proliferation and maintenance of genomic integrity has thus been investigated for its clinical relevance as an independent prognosticator in glioma. Expression of the protein in tumor tissue and in plasma of 72 diffuse glioma patients (astrocytoma) grade II-IV was determined and compared with relevant controls using immunofluorescence-immunohistochemistry and enzyme-linked immuno-sorbent assay. Appropriate statistical tests were applied to establish a correlation between on-site tumor and circulating levels of the marker and its independence of covariates. Expression of the marker in glioma tissues was significantly different from controls (p < 0.0001) and could discriminate within grades with ≥80% sensitivity. The tissue and plasma levels were positively associated with grades (r = 0.8845, p < 0.0001) and (r = 0.2834, p = 0.0158) respectively, while an inverse correlation with overall survival (r = -0.6558, p < 0.0001) and (r = -0.3941, p = 0.0006) respectively, was recorded. Plasma hTERT was significantly correlated with corresponding intra-tumor expression of hTERT (r = 0.2794, p = 0.0175). Multivariate Cox-regression identified plasma hTERT (p < 0.0005) as a prognostic factor; not associated with age, site or extent of resection (p > 0.05). This is the first experimental evidence for association of higher plasma levels of hTERT with overall survival in both low and high grade glioma. | 10.1007/s11060-017-2578-6 |
pubmed_1109_2023 | Endoscopic therapy is recommended as the first-line therapy for painful chronic pancreatitis with an obstacle on the main pancreatic duct (MPD). The clinical response should be evaluated at 6 to 8 weeks. Calcified stones that obstruct the MPD are first treated by extracorporeal shockwave lithotripsy; dominant MPD strictures are optimally treated with a single, large, plastic stent that should be exchanged within 1 year even in asymptomatic patients. Pancreatic pseudocysts for which therapy is indicated and are within endoscopic reach should be treated by endoscopy. | pubmed_1109_2023 |
others_413_23289 | In early 2020, coronavirus disease 2019 (COVID-19) was declared a public health emergency and a combination of lockdown and social distancing measures were put in place across the globe. Many children, adolescents and adults have experienced adverse mental health effects related to the pandemic and its impact on daily life, although the long-term impact on individuals and health systems is not well understood.
MethodsThis cross-sectional study was based on data from 2018-2021 collected via medical records from our hospital. Admissions were transformed into time-series data, and models were generated to analyze changes in admission rates for mental health emergencies in 2020 and 2021 compared to previous years.
ResultsOf 1906 inpatient encounters among 1543 unique patients seen by the Child and Adolescent Psychiatry Consultation-Liaison service, there was a decrease in overall admissions beginning in March 2020, coinciding with statewide lock down due to the COVID-19 pandemic. In April 2020, admissions were reduced 36% compared to average admissions from 2018-2019. By 2021, overall admissions were significantly higher than for the previous three years. Similarly, the count of suicide attempts was significantly higher in 2021 compared to previous years. The rate of patients admitted to inpatient facilities upon discharge was significantly higher during the COVID-19 pandemic period.
ConclusionAdmissions for mental health emergencies fluctuated during the period associated with the COVID-19 pandemic across an array of diagnoses. Increases in admissions and severity of mental health emergencies during COVID-19 may reflect a detrimental impact of the pandemic on the mental health of children, as well as unmet needs during this tim | 10.1101/2021.08.11.21261712 |
pubmed_926_10518 | The genome of red clover necrotic mosaic virus is divided into two positive-stranded RNA molecules of RNA1 and RNA2, which have no 5' cap structure and no 3' poly(A) tail. Previously, we showed that any mutations in the cis-acting RNA replication elements of RNA2 abolished its cap-independent translational activity, suggesting a strong link between RNA replication and translation. Here, we investigated the functions of the 5' untranslated region (UTR) of RNA2 and revealed that the basal stem-structure (5'BS) predicted in the 5' UTR is essential for robust RNA replication. Interestingly, RNA2 mutants with substitution or deletion in the right side of the 5'BS showed strong translational activity, despite their impaired replication competency. Furthermore, nucleotide sequences other than the 5'BS of the 5' UTR were essential to facilitate the replication-associated translation. Overall, these cis-acting RNA elements seem to coordinately regulate the balance between RNA replication and replication-associated translation. | 10.1016/j.virol.2017.09.008 |
others_375_5564 | Predation by frogs, site selection and site usage during oviposition by a small dragonfly were studied. Data were collected under natural conditions and in a large outdoor field-cage. Sympetrum danae oviposits in flight as a pair (tandem) following copulation, as a released post-tandem female or as an unattended female. Under natural conditions 14% of all females that started oviposition in tandem and 10% of all solitary females were killed by frogs, while this was so for only 3% of all males in tandem. Ovipositing post-tandem females were less frequently attacked by frogs than females that were not seen to have mated previously. Sites with Sphagnum were preferred. Substrate selection was probably mainly visual as some dragonflies were also attracted to a structurally similar, but non-aquatic, moss. Sites were chosen in relation to thermoregulatory requirements: south-facing sites were used at low ambient temperatures late in the season and north-facing sites at high ambient temperatures early in the season. Pairs searched longer for a suitable site at higher ambient temperatures and preferred sites with ovipositing individuals on them. They were more hesitant about choosing a site when frogs were present than when they were absent. Compared with pairs or solitary/unmated females, unattended females were more likely to oviposit at the site where the male released them. The results are discussed in terms of optimized habitat selection for larval development at minimized oviposition costs. © 1990 The Association for the Study of Animal Beha | 10.1016/S0003-3472(05)80696-7 |
pubmed_827_9566 | PURPOSE
We assessed the accuracy of a point-of-care blood gas analyzer in providing data from saline samples obtained by gastrointestinal tonometry (Tonometrics Catheter; Tonometrics Division, Instrumentarium, Helsinki, Finland) for the calculation of intramucosal pH (pHi) and the P(CO)(2) gap (intramucosal P(CO)(2) - Pa(CO)(2)).
METHODS
We compared the point-of-care analyzer (Opti; AVL Medical Instruments, Schaffhausen, Switzerland; "Opt") with a conventional analyzer (Compact 2 AVL Medical Instruments, Schaffhausen; "Elect") in a clinical study (Elect being taking as the standard). In an in vitro study, P(CO)(2) data of tonometer saline (Pr(CO)(2)) from Opt and Elect were compared with P(CO)(2) data from a continuous air tonometer (Tonocap Tonometrics Division, Instrumentarium) for a bottle containing a mixed P(CO)(2) gas. Data were evaluated by the Bland-Altman method.
RESULTS
In the clinical study, the bias (B) and precision (P) were: B = 0.223 and P = 0.056 for pHi, B = -14.0 and P = 2.43 (mmHg) for Pr(CO)(2), and B = -16.7 and P = 2.6 (mmHg) for the P(CO)(2) gap ( n = 27). In the in vitro study, the bias between the two values (Pr(CO)(2) and bottle P(CO)(2)) was -1.98 mmHg and precision was 1.23 mmHg for Elect, but for Opt, these values were -22.09 mmHg and 3.15 mmHg, respectively ( n = 18).
CONCLUSION
Opt is not suitable for measuring pHi and the P(CO)(2) gap because it does not provide an accurate P(CO)(2) for tonometry saline. | 10.1007/s00540-003-0209-1 |
pubmed_744_20847 | Since the first case of HIV/AIDS was identified in 1986 in Malaysia, the number of infected individuals has increased steadily each year, so that by the end of 2002 the cumulative number of people living with HIV/AIDS was 57,835 (51,256 with HIV and 6,579 with AIDS), with 5,676 AIDS deaths. The epidemic in Malaysia, currently in a concentrated epidemic stage, is primarily fueled by drug use, but there is ample evidence that heterosexual transmission has increased over the last few years. A strategic plan that includes prevention, care, support, and treatment run by both the government and nongovernmental organizations has been in place since the beginning of the epidemic. However, Malaysia will need to take a more pragmatic approach to reduce new infections (which numbered 19 each day in 2002) among the youth on whom the country relies for development. Leaders need to recognize that HIV/AIDS is not just a health issue, but also a socioeconomic concern that can eliminate all the developmental gains achieved over the years. Working together, Malaysians can overcome the epidemic, but there is a need to act quickly and to act in effective ways so that the devastating effects (already evident in the number of AIDS orphans and widows) can be reduced. | 10.1521/aeap.16.3.5.100.35532 |
others_235_13572 | The innervation of the spermatheca and demonstration of neural control of spermathecal contractions in Locusta migratoria was illustrated using anterograde and retrograde fills, combined with electrophysiological stimulation and recording. The anterior portion of the spermatheca receives innervation via the receptaculum seminis nerve (N2B2) from two large ventral neurons and one dorsal neuron. All were bilaterally paired and situated in the VIIIth abdominal ganglion. Three ventral bilaterally paired neurons situated in the VIIIth abdominal ganglion also provide innervation to the posterior portion of the spermatheca via the ductus seminalis aperture nerve (N2B3). Six DUM neurons, located in the VIIIth abdominal ganglion, in addition to two centroposteriorly situated DUM neurons in the VIIth abdominal ganglion, are also associated with these two nerves. N2B4 also provides innervation to the posterior portion of the spermatheca. N2B6b is associated with sensory cells identified in the anterior lateral regions of the genital chamber. The spermatheca contracts spontaneously, with peristaltic contractions beginning at the spermathecal sac and continuing along the length of the spermathecal duct. However electrical stimulation of the ventral ovipositor nerve (VON or N2B), receptaculum seminis nerve (N2B2) and the ductus seminalis aperture nerve (N2B3) indicates that contractions are also under neural control. In particular contractions of the spermathecal sac, coil duct and anterior straight duct are initiated via motor projections from the receptaculum seminis nerve (N2B2) and posterior straight duct contractions are controlled by motor input from the ductus seminalis aperture nerve (N2B3). The results suggest that spermathecal contractions of the anterior and posterior portions of the spermatheca are under separate neural control. © 2000 Elsevier Science L | 10.1016/S0022-1910(99)00116-X |
pubmed_363_13159 | The acid-base status of precipitation is a result of a balance between acidifying compounds--mainly oxides of sulfur and nitrogen--and alkaline compounds--mainly ammonia and alkaline material in windblown soil dust. We use current models of the global atmospheric distribution of such compounds to estimate the geographical distribution of pH in precipitation and of the rate of deposition of hydrogen ion or bicarbonate ion. The lowest pH values--mainly due to high concentration of sulfuric acid--occur in eastern parts of North America, Europe, and China. A comparison with observed pH values shows fair agreement in most parts of the world. However, in some areas, e.g. western North America, southwestern Europe, and northern China the estimated pH is too low, indicating that we have underestimated the deposition flux of alkaline material, probably mainly CaCO3. Our neglect of organic acids may have contributed to an overestimate of pH especially in certain tropical areas. To illustrate the potential effects of acidifying deposition on nitrogen saturated terrestrial ecosystems we also calculate the deposition of "potential acidity" that takes into account the microbial transformation of ammonium to nitrate in such ecosystems, resulting in the release of hydrogen ion. Compared to the deposition of acidity, with its maxima over Europe, eastern North America, and southern China, the deposition of potential acidity exhibits an additional maximum in India and Bangladesh and in several other smaller hot spots where the cycling of ammonia is enhanced by a dense cattle population. To the extent that soils in these areas of high potential acidity deposition actually become nitrogen saturated a depletion of base cations and other changes in soil chemistry and biology should be expected. Potential problem areas forfuture soil acidification include several regions with sensitive soils in southern, southeastern, and eastern Asia as well as in central parts of South America. | 10.1021/es020057g |
pubmed_415_9171 | QUESTION UNDER STUDY
The study has following objectives: 1) to determine the incidence of higher-order multiple births from 2005 to 2008 in Switzerland and its evolution over the last twenty years, and 2) to analyse the neonatal outcome and its change over the last two decades.
METHODS
Data on higher-order multiple births were retrospectively obtained from Swiss obstetric and neonatal hospitals and compared with results from the first two national surveys.
RESULTS
The incidence of higher-order multiple births was 35.3/100,000 live births for triplets, 0.7/100,000 for quadruplets and 0.3/100,000 for quintuplets. All newborns were premature with a median gestational age of 32 1/7 weeks for triplets, 29 2/7 weeks for quadruplets and 28 4/7 weeks for quintuplets. 94% of triplets and all quadruplets and quintuplets survived the neonatal period. Over the last two decades, the incidence of quadruplet and quintuplet births has fallen, while that of triplet births has risen by 40%. The perinatal mortality of triplets has decreased and the neonatal morbidity, mainly respiratory distress, has remained constant.
CONCLUSION
Higher-order multiple births have a high morbidity that has not improved over the last two decades. The incidence of higher-order multiple births is still increasing, which demonstrates that reproductive medicine in Switzerland is not yet sufficiently controlled and monitored. | pubmed_415_9171 |
pubmed_386_10883 | AIM
Energy drink consumption has been associated with a variety of health risk behaviours, yet little research has explored the relationship between energy drinks and dietary behaviours of emerging adults. Therefore, the purpose of this study was to explore the relationship between energy drink consumption and dietary behaviours among energy drink users and non-users within a sample of college youth.
METHODS
College freshmen (n = 585, m age = 18.7 years; 47% non-Hispanic White, 20.9% Hispanic, 25.5% Asian, 2.7% non-Hispanic Black and 4.4% other; 56% female), at a large, southwest university self-reported their energy drink consumption in the past week and a variety of dietary behaviours, including past week soda, diet soda, pre-packaged salty snacks, pre-packaged sweet snacks, fast food, restaurant food, frozen food, fruits, vegetables, milk and breakfast consumption. Linear regression analyses were run to determine associations between energy drink consumption and dietary behaviour among users and non-users of energy drinks. Analyses controlled for gender, race/ethnicity and body mass index (BMI).
RESULTS
Overall, 17.5% of students had consumed energy drinks in the past week. Energy drink users were more likely to be male, White and have a greater BMI. Students also reported low past week intake of fruits, vegetables, milk and breakfast. Past week energy drink consumption was associated with increased soda and frozen meal consumption.
CONCLUSION
Given a rapidly expanding energy drink market, future dietary interventions among college youth may want to consider the implications of energy drinks, as results of this study suggest consumption of these beverages is associated with unhealthy dietary behaviours and a greater BMI. | 10.1177/1757913914565388 |
pubmed_702_24413 | Anthropoid primate models offer opportunities to study genetic influence on alcohol consumption and alcohol-related intermediate phenotypes in socially and behaviorally complex animal models that are closely related to humans, and in which functionally equivalent or orthologous genetic variants exist. This review will discuss the methods commonly used for performing candidate gene-based studies in rhesus macaques in order to model how functional genetic variation moderates risk for human psychiatric disorders. Various in silico and in vitro approaches to identifying functional genetic variants for performance of these studies will be discussed. Next, I will provide examples of how this approach can be used for performing candidate gene-based studies and for examining gene by environment interactions. Finally, these approaches will then be placed in the context of how function-guided studies can inform us of genetic variants that may be under selection across species, demonstrating how functional genetic variants that may have conferred selective advantage at some point in the evolutionary history of humans could increase risk for addictive disorders in modern society. | 10.1016/j.ymeth.2009.05.014 |
pubmed_20_15822 | Nanometer-thin sheets of 2D Ti3C2Tx (MXene) have been assembled into freestanding or supported membranes for the charge- and size-selective rejection of ions and molecules. MXene membranes with controllable thicknesses ranging from hundreds of nanometers to several micrometers exhibited flexibility, high mechanical strength, hydrophilic surfaces, and electrical conductivity that render them promising for separation applications. Micrometer-thick MXene membranes demonstrated ultrafast water flux of 37.4 L/(Bar·h·m(2)) and differential sieving of salts depending on both the hydration radius and charge of the ions. Cations with a larger charge and hydration radii smaller than the interlayer spacing of MXene (∼6 Å) demonstrate an order of magnitude slower permeation compared to single-charged cations. Our findings may open a door for developing efficient and highly selective separation membranes from 2D carbides. | 10.1021/acs.jpclett.5b01895 |
pubmed_968_11866 | Zona incerta (ZI), a largely inhibitory subthalamic region connected with many brain areas, has been suggested to serve as an integrative node for modulation of behaviors and physiological states, such as fear memory conditioning and aversion responses. It is, however, unclear whether ZI regulated the repeated social defeat stress (RSDS)-induced social conditioned place aversion (CPA) and post-traumatic stress disorder (PTSD)-like behaviors. In this study, the function of ZI was silenced via bilateral injection of tetanus toxin light chain (Tet-tox), a neurotoxin that completely blocks the evoked synaptic transmissions, expressing adeno-associated viruses (AAVs). We found ZI silencing: (1) significantly blocked the expression of RSDS-induced social CPA with no effect on the innate preference; (2) significantly enhanced the anxiety level in mice experienced RSDS with no effect on the locomotion activity; (3) altered the PTSD-associated behaviors, including the promotion of spatial cognitive impairment and the preventions of PPI deficit and social avoidance behavior. These effects were not observed on non-stressed mice. In summary, our results suggest the important role of ZI in modulating RSDS-induced social CPA and PTSD-like behaviors. | 10.3389/fnbeh.2021.743484 |
pubmed_999_13842 | Early brain lesions which produce cerebral palsy (CP) may affect the development of walking. It is unclear whether or how neuromuscular control, as evaluated by muscle synergy analysis, differs in young children with CP compared to typically developing (TD) children with the same walking ability, before and after the onset of independent walking. Here we grouped twenty children with (high risk of) CP and twenty TD children (age 6.5-52.4 months) based on their walking ability, supported or independent walking. Muscle synergies were extracted from electromyography data of bilateral leg muscles using non-negative matrix factorization. Number, synergies' structure and variability accounted for when extracting one (VAF1) or two (VAF2) synergies were compared between CP and TD. Children in the CP group recruited fewer synergies with higher VAF1 and VAF2 compared to TD children in the supported and independent walking group. The most affected side in children with asymmetric CP walking independently recruited fewer synergies with higher VAF1 compared to the least affected side. Our findings suggest that early brain lesions result in early alterations of neuromuscular control, specific for the most affected side in asymmetric CP. | 10.3390/s21082714 |
pubmed_602_21090 | In a novel biosensing approach, a stearyl-[small beta]-d-glucopyranoside layer is formed by self-organization at the interface between a solvent polymeric membrane and the aqueous sample phase and its interaction with concanavalin A is detected by electric impedance spectroscopy. | 10.1039/b401864h |
pubmed_373_8194 | PURPOSE
The aim of the present study was to evaluate the use of defaeco-peritoneography in diagnosing rectal intussusception as distinct from mucosal folds in the rectum, and rectal prolapse as distinct from mucosal prolapse.
MATERIAL AND METHODS
Fifty-seven patients with defaecation disorders were examined by means of defaeco-peritoneography.
RESULTS
Twenty-three patients had rectal intussusception and 7 patients had rectal prolapse at defaeco-peritoneography. All these patients had a rectal peritoneocele in the serosal ring-pocket of the rectal intussusception or in the rectal prolapse. Twenty-seven patients had neither rectal intussusception nor rectal prolapse and none of these patients had a rectal peritoneocele.
CONCLUSION
The present study demonstrated that only patients with a rectal intussusception or rectal prolapse have a rectal peritoneocele. Defaeco-peritoneography therefore offers correct diagnosis of rectal intussusception as distinct from mucosal folds in the rectum, and of rectal prolapse as distinct from mucosal prolapse. | 10.1080/02841859709174390 |
pubmed_251_7097 | The role of nitric oxide (NO) in the activity of cyclooxygenase (COX) in cultured canine tracheal epithelium was studied. Tracheal epithelium spontaneously released prostaglandin E2 (PGE2), which is a product of COX. The release of PGE2 was increased by bradykinin and was decreased by two NO synthase inhibitors: NG-nitro-L-arginine methyl ester and NG-monomethyl-L-arginine. That decrease was reversed in the presence of L-arginine. Chrolpromadin, but not aminoguanidine, inhibited PGE2 production, which suggests that constitutive NO synthase is involved. Two stable NO donors, sodium nitroprusside and S-nitroso-N-acetyl DL-penicillamine, also increased the production of PGE2. These effects were abolished by coincubation with hemoglobin, which binds and inactivates NO, but not by methylene blue, an inhibitor of soluble guanylate cyclase. NADPH diaphorase histochemistry of cultured tracheal cells revealed activity in the periphery of the cytoplasm. These results suggest that, in cultured canine tracheal epithelium, NO directly interacts with COX to regulate PGE2 production. | pubmed_251_7097 |
pubmed_571_17585 | The combination of sodium hypochlorite (NaOCl) and chlorhexidine (CHX) forms a precipitate. The aim of this study was to evaluate the effect of irrigating root canals with a combination of NaOCl and CHX on root dentin and dentinal tubules by using the environmental scanning electron microscope (ESEM) and a computer program (Photoshop CS2). Forty-four extracted single-rooted human teeth were instrumented and irrigated with both NaOCl and CHX to produce a precipitate. Root canal surfaces were analyzed with the ESEM. The amount of remaining debris and number of patent tubules were determined. There were no significant differences in remaining debris between the negative control group and the experimental groups. There were significantly fewer patent tubules in the experimental groups when compared with the negative control group. The NaOCl/CHX precipitate tends to occlude the dentinal tubules. Until this precipitate is studied further, caution should be exercised when irrigating with NaOCl and CHX. | 10.1016/j.joen.2007.11.006 |
pubmed_448_2866 | OBJECTIVE
Pulse arrival time (PAT) is a potential main feature in cuff-less blood pressure (BP) monitoring. However, the precise relationship between BP parameters and PAT under varying conditions lacks a complete understanding. We hypothesize that simple test protocols fail to demonstrate the complex relationship between PAT and both SBP and DBP. Therefore, this study aimed to investigate the correlation between PAT and BP during two exercise modalities with differing BP responses using an unobtrusive wearable device.
METHODS
Seventy-five subjects, of which 43.7% had a prior diagnosis of hypertension, participated in an isometric and dynamic exercise test also including seated periods of rest prior to, in between and after. PAT was measured using a prototype wearable chest belt with a one-channel electrocardiogram and a photo-plethysmography sensor. Reference BP was measured auscultatory.
RESULTS
Mean individual correlation between PAT and SBP was -0.82 ± 0.14 in the full protocol, -0.79 ± 0.27 during isometric exercise and -0.77 ± 0.19 during dynamic exercise. Corresponding correlation between PAT and DBP was 0.25 ± 0.35, -0.74 ± 0.23 and 0.39 ± 0.41.
CONCLUSION
The results confirm PAT as a potential main feature to track changes in SBP. The relationship between DBP and PAT varied between exercise modalities, with the sign of the correlation changing from negative to positive between type of exercise modality. Thus, we hypothesize that simple test protocols fail to demonstrate the complex relationship between PAT and BP with emphasis on DBP. | 10.1097/MBP.0000000000000577 |
pubmed_83_9640 | Four experiments investigated the extent to which a limited pool of resources can be shared between different tasks performed simultaneously when it is efficient to do so. The experiments used a prioritized processing paradigm, in which stimuli for both a primary task and a background task were presented in each trial. If the primary-task stimulus required a response in a trial, participants made only that response. If the primary-task stimulus did not require a response, participants responded to the background task. The main manipulation was the relative probability that a response would be required to the primary versus background task. In some blocks, the majority of trials required responses to the primary task (Experiments 1 and 2: 80%; Experiments 3 and 4: 60%), whereas in other blocks the majority required responses to the background task. Background-task responses were substantially faster in blocks where they were more likely to be required, consistent with the idea that more capacity was allocated to them in these blocks. Backward compatibility effects on primary-task responses and stimulus-onset asynchrony effects on background-task responses provided further evidence of greater capacity allocation to the background task when there was a higher probability of responding to it. The results support the view that two tasks can be processed in parallel, with resources divided between them, when it is efficient to do so. | 10.3758/s13414-020-02143-7 |
pubmed_918_9307 | Cerebral malaria (CM) is one of the most severe complications of Plasmodium falciparum infection. There is evidence that repeated parasite exposure promotes resistance against CM. However, the immunological basis of this infection-induced resistance remains poorly understood. Here, utilizing the Plasmodium berghei ANKA (PbA) model of experimental cerebral malaria (ECM), we show that three rounds of infection and drug-cure protects against the development of ECM during a subsequent fourth (4X) infection. Exposure-induced resistance was associated with specific suppression of CD8+ T cell activation and CTL-related pathways, which corresponded with the development of heterogeneous atypical B cell populations as well as the gradual infection-induced generation and maintenance of high levels of anti-parasite IgG. Mechanistically, transfer of high-titer anti-parasite IgG did not protect 1X infected mice against ECM and depletion of atypical and regulatory B cells during 4X infection failed to abrogate infection-induced resistance to ECM. However, IgMi mice that were unable to produce secreted antibody, or undergo class switching, during the repeated rounds of infection failed to develop resistance against ECM. The failure of infection-induced protection in IgMi mice was associated with impaired development of atypical B cell populations and the inability to suppress pathogenic CD8+ T cell responses. Our results, therefore, suggest the importance of anti-parasite antibody responses, gradually acquired, and maintained through repeated Plasmodium infections, for modulating the B cell compartment and eventually suppressing memory CD8+ T cell reactivation to establish infection-induced resistance to ECM. | 10.3389/fimmu.2019.00248 |
pubmed_19_14977 | Hepatocellular carcinoma (HCC) is frequently associated with abnormalities in cell cycle regulation, leading to increased activity of cyclin-dependent kinases (Cdks) due to the loss, or low expression of, Cdk inhibitors. In this study, we showed that ibulocydine (an isobutyrate prodrug of the specific Cdk inhibitor, BMK-Y101) is a candidate anti-cancer drug for HCC. Ibulocydine has high activity against Cdk7/cyclin H/Mat1 and Cdk9/cyclin T. Ibulocydine inhibited the growth of HCC cells more effectively than other Cdk inhibitors, including olomoucine and roscovitine, whereas ibulocydine as well as the other Cdk inhibitors and BMK-Y101 minimally influenced the growth of normal hepatocyte cells. Ibulocydine induced apoptosis in HCC cells, most likely by inhibiting Cdk7 and Cdk9. In vitro treatment of HCC cells with ibulocydine rapidly blocked phosphorylation of the carboxyl-terminal domain (CTD) of the large subunit of RNA polymerase II, a process mediated by Cdk7/9. Anti-apoptotic gene products such as Mcl-1, survivin, and X-linked IAP (XIAP) are crucial for the survival of many cell types, including HCC. Following the inhibition of RNA polymerase II phosphorylation, ibulocydine caused rapid down-regulation of Mcl-1, survivin, and XIAP, thus inducing apoptosis. Furthermore, ibulocydine effectively induced apoptosis in HCC xenografts with no toxic side effects. These results suggest that ibulocydine is a strong candidate anti-cancer drug for the treatment of HCC. | 10.1074/jbc.M110.209551 |
pubmed_948_3418 | An unusual and grotesque congenital deformity of the head involving a duplication of the CNS and the anlage of a third eye in dextroposition (double monster) in a 54 day old kitten, born by caesarean section, is described. The malformation is thought to be caused by exogenous teratogenic influences during the early phase of blastogenesis. | pubmed_948_3418 |
pubmed_1070_1956 | The purpose of this study was to determine the degree of criterion validity and intra-tester reliability of humeral head palpation in subjects with shoulder pathology. The study also sought to determine whether there was any effect of arm position on humeral head position in subjects with shoulder pathology. In a same day repeated measures design, 27 subjects had the distance between the most anterior portion of the humeral head and the anterior edge of the acromion measured by a radiologist using MRI (supine), and by a physiotherapist using palpation and photography (supine, sit with arm in neutral and in abduction). The Standard Error of Measurement (SEM) for the difference between MRI and palpation ranged from 3.4 to 4.4mm and correlated significantly with palpation measures in sit (r=0.57-0.64, p<or=0.002). The Intraclass Correlation Coefficients (ICCs) and SEMs for intra-tester reliability were 0.85 and 2.6mm for supine, 0.86 and 2.2mm for sit (glenohumeral neutral), and 0.91 and 3.0mm for sit (glenohumeral abduction). Significant differences between the positions of sit neutral and sit with abduction were found (p<0.001). Humeral head palpation in sit abduction demonstrates sufficient validity and reliability for clinical use. | 10.1016/j.math.2008.06.004 |
pubmed_815_6961 | Familial hemiplegic migraine (FHM) is a distinctive form of migraine with an autosomal dominant mode of inheritance. The migraine-like attacks are associated with transient hemiparesis. A locus for FHM has recently been assigned to chromosome 19 by linkage mapping. In the present study, five unrelated pedigrees with multiple members suffering from hemiplegic migraine were investigated. In two of the pedigrees additional symptoms, cerebellar ataxia and benign neonatal convulsions, respectively, were observed in affected members. Three pedigrees showed linkage to loci D19S391, D19S221, and D19S226 at chromosome 19p13. Haplotyping suggested a location of a FHM gene between D19S391 and D19S221. In the two remaining families, evidence against linkage was found. These results confirm the localization of a gene for familial hemiplegic migraine to the short arm of chromosome 19, but locus heterogeneity not corresponding to the observed clinical heterogeneity is likely to exist. | 10.1006/geno.1994.1340 |
pubmed_369_18940 | Our previous proteomics study revealed that long chain acyl CoA synthetase 1 (ACSL1) and gelsolin (GSN) are oppositely regulated in white adipose tissue of diet-induced obese rats. To firmly establish these proteins as mediators of adipogenic and/or lipogenic events, we efficiently knocked down the Acsl1 and Gsn genes using siRNA in 3T3-L1 adipocyte cells. Expectedly, Acsl1 knockdown stimulated expression of lipogenic genes. Interestingly, Gsn knockdown suppressed expression of lipogenic genes but strikingly increased that of Tnfα and Il6, which may have connections with lipolytic capacity of these genes. Conclusively, we provide clear evidence that ACSL1 and GSN are potential target proteins in the context of obesity. | 10.1016/j.bbrc.2012.03.038 |
pubmed_530_22716 | Starting from Rowe's equation of motion we derive extended random phase approximation (ERPA) equations for excitation energies. The ERPA matrix elements are expressed in terms of the correlated ground state one- and two-electron reduced density matrices, 1- and 2-RDM, respectively. Three ways of obtaining approximate 2-RDM are considered: linearization of the ERPA equations, obtaining 2-RDM from density matrix functionals, and employing 2-RDM corresponding to an antisymmetrized product of strongly orthogonal geminals (APSG) ansatz. Applying the ERPA equations with the exact 2-RDM to a hydrogen molecule reveals that the resulting (1)Σ(g)(+) excitation energies are not exact. A correction to the ERPA excitation operator involving some double excitations is proposed leading to the ERPA2 approach, which employs the APSG one- and two-electron reduced density matrices. For two-electron systems ERPA2 satisfies a consistency condition and yields exact singlet excitations. It is shown that 2-RDM corresponding to the APSG theory employed in the ERPA2 equations yields excellent singlet excitation energies for Be and LiH systems, and for the N(2) molecule the quality of the potential energy curves is at the coupled cluster singles and doubles level. ERPA2 nearly satisfies the consistency condition for small molecules that partially explains its good performance. | 10.1063/1.4766934 |
pubmed_955_12284 | Brain imaging techniques will in the future play an important role in the assessment of patients with neurogenerative disorders such as Alzheimer's disease (AD). An early diagnosis of AD is today hampered by lack of reliable diagnostic markers. Positron emission tomography (PET) permits the quantification and three-dimensional imaging of physiological variables. This provides the clinician with a non-invasive imaging technique which allows in vivo quantification of physiological processes in AD underlying dysfunction of cognition. PET studies regarding changes in cerebral blood flow and metabolism are rather consistent at least in moderate/advanced cases of AD. How early in the progress of the disease deficits in these parameters can be observed is still an open question. Longitudinal studies will here be important and especially in individuals with a family history of AD. Since deficits in cholinergic neurotransmission have been measured in autopsy AD brains attempts have also been made to visualized cholinergic activity in vivo. Nicotinic and muscarinic receptors have been visualized in normal and AD brains. A reduced uptake and binding of [11C]nicotine in the temporal and frontal cortices have been measured in AD patients by PET. Few treatment studies in AD have been evaluated by PET. Long-term treatment with the cholinesterase inhibitor tacrine increase the uptake of [11C]nicotine. Significant reduction in uptake between the two enantiomers (S)(-) and (R)(+)-[11C]nicotine has been observed compatible with a restoration of nicotinic receptors. Tacrine also significantly increased the glucose metabolism. PET studies indicate that long-term tacrine treatment in AD patients with mild dementia improves functional activities in brain. When an AD patient with moderate dementia was treated with nerve growth factor (NGF) PET studies revealed increase in cortical blood flow and nicotinic receptors. PET studies will in the future play an important role in the evaluation of new therapeutic drug strategies in AD. | 10.1016/0166-4328(93)90138-g |
pubmed_346_13775 | The results obtained in the analysis of 130 thrombocytopenic patients with a radioimmunoassay (RIA) for platelet-associated IgG (PA-IgG) and the platelet suspension immunofluorescence test (PIFT) were compared. The RIA was positive in 33 of 41 (82.9%) patients with idiopathic thrombocytopenia (ITP) and in 51 of 79 (64.4%) patients with secondary thrombocytopenia (STP). The PIFT was positive in 37 of the 41 (90.2%) ITP patients and in 57 of the 79 (72.2%) STP patients. Sensitivity and specificity for the diagnosis of ITP of both tests were comparable: 82.9 and 40.9% for the PA-IgG(RIA) and 90.2 and 36.7% for the PIFT. A significant positive correlation was observed between the mean amount of PA-IgG measured and the height of PIFT scores with anti-IgG. Of 38 discrepancies between PA-IgG(RIA) and PIFT with anti-IgG, 15 were due to borderline results, 17 were associated with abnormal platelet-size distribution and 20 were associated with occurrence of IgM antibodies. These results suggest influences of platelet fragments and/or aggregates on accurate measurement of PA-IgG. Both fragments and aggregates escape from accurate platelet counting, while their contribution to the total IgG content remains. Therefore, a falsely elevated PA-IgG (RIA) may be measured. | 10.1111/j.1423-0410.1987.tb04942.x |
pubmed_125_3359 | This study was aimed at examining the impact of common types of physical efforts used to determine the aerobic and anaerobic performance of the participants on the complement system in their peripheral blood. Fifty-one physically active young males aged 16 years old (range 15-21 years) were divided into two age groups (younger, 15-17 years old and older, 18-21 years old) and performed two types of intensive efforts: aerobic (endurance; 20-m shuttle run test; Beep) and anaerobic (speed; repeated speed ability test; RSA). Venous blood samples were collected before and after each exercise (5 and 60 min) to profile the complement system components, namely the levels of C2, C3, C3a, iC3b, and C4. The endurance effort caused a decrease in the post-test C3 (p < 0.001 for both age groups) and increase in post-test C3a (p < 0.001 and p < 0.01 for the younger and older group, respectively), recovery iC3b (p < 0.001 and p < 0.05 for younger and older group, respectively), recovery C2 (p < 0.01 for both age groups), and post-test C4 (p < 0.05 and p < 0.01 for the younger and older group, respectively) levels, while the speed effort caused a decrease only in the post-test C2 (p < 0.05 for younger participants) and post-test C4 levels (p < 0.001 and p < 0.01 for the younger and older group, respectively) and an increase in the recovery C3a level (p < 0.05). Our study provides evidence that different types of physical effort promote different immune responses in physically active young men. Aerobic exercise induced the activation of an alternative pathway of the complement system, whilst the anaerobic effort had little influence. A better understanding of the post-exercise immune response provides a framework to prescribe physical activity to achieve different health outcomes. | 10.3390/jcm9082357 |
pubmed_713_13281 | BACKGROUND
Monoclonal antibodies with high efficiency and specificity are one of the best strategies to diagnose and treat a variety of diseases such as cancer, autoimmunity, and inflammatory diseases. The market for monoclonal therapeutic antibodies (MTAs) has grown dramatically in the past decade.
OBJECTIVE
Given the importance of these issues, developing countries spend a high cost on importing or producing MTAs annually. This study intends to examine the market of monoclonal therapeutic antibodies in Iran and predict the future growth rate of this market using the obtained data.
METHODS
Data on the status of MTAs in the country (from 2008 to 2018) were obtained from the Food and Drug Deputy of Mazandaran University of Medical Sciences. The market status of MTAs was studied based on the dosage forms, application, and price. Then, the market outlook was predicted up to year 2025.
RESULTS
The results showed that 58.8% of all MTAs were humanized, and 86% of all antibody-based drugs were used to treat cancer. Sales of MTA-based medications will reach $454 million by 2025 and are projected to grow significantly in the future.
CONCLUSION
Given the increasing technology of the production of MTAs and their use in targeted therapies worldwide, their consumption market in Iran is expected to grow significantly. | 10.1155/2021/5569590 |
pubmed_48_4131 | The above article from Acta Neurologica Scandinavica, published online on 7 April 2005 in Wiley Online Library (wileyonlinelibrary.com) and in Volume 111, pp. 329-332, has been retracted by agreement between the journal Editor in Chief, Professor Elinor Ben-Menachem, and John Wiley & Sons Ltd. The article has been retracted because a similar article had previously been published in the Jugoslovenska medicinska biohemija in 2003. The authors presumed that since the journal was no longer existing, they felt the need to re-publish their work in Acta Neuorologica Scandinavica. However, in the consideration of the Journal, this constitutes dual publication. References SelakovićVM, JovanovićMD, MihajlovićR, RadenovićLLJ. Cytochrome c oxidase in patients with acute ischaemic brain disease. Jugoslovenska medicinska biohemija. 2003;22:329-334. SelakovićVM, JovanovićMD, MihajlovićRR, RadenovićLLJ. Dynamics of cytochrome c oxidase activity in acute ischemic stroke. Acta Neurol Scand. 2005;111:329-332. | 10.1111/ane.12643 |
pubmed_339_18108 | NB is short auxiliary protein with ca. 100 amino acids, encoded in the viral genome of influenza B. It is believed to be similar to M2 from influenza A and Vpu from HIV-1 in that it demonstrates ion channel activity. Channels formed by the protein can be blocked by amantadine. We have synthesized the putative transmembrane segment of NB (IRG S20 IIITICVSL I30 VILIVFGCI A40 KIFI (NB, Lee)). Reconstituted in a lipid bilayer, the peptide shows channel activity. The addition of amantadine leads to dose-dependent loss of channel activity. Channel blocking is reversible. Channel behaviour of the peptide in the presence of amantadine is in accordance with findings for the intact channel. Thus, the synthetic transmembrane peptide captures the ion channel activity of the intact NB protein. | 10.1007/s002490100157 |
pubmed_41_10763 | Protein adsorption and assembly at interfaces provide a potentially versatile route to create useful constructs for fluid compartmentalization. In this context, we consider the interfacial assembly of a bacterial biofilm protein, BslA, at air-water and oil-water interfaces. Densely packed, high modulus monolayers form at air-water interfaces, leading to the formation of flattened sessile water drops. BslA forms elastic sheets at oil-water interfaces, leading to the production of stable monodisperse oil-in-water microcapsules. By contrast, water-in-oil microcapsules are unstable but display arrested rather than full coalescence on contact. The disparity in stability likely originates from a low areal density of BslA hydrophobic caps on the exterior surface of water-in-oil microcapsules, relative to the inverse case. In direct analogy with small molecule surfactants, the lack of stability of individual water-in-oil microcapsules is consistent with the large value of the hydrophilic-lipophilic balance (HLB number) calculated based on the BslA crystal structure. The occurrence of arrested coalescence indicates that the surface activity of BslA is similar to that of colloidal particles that produce Pickering emulsions, with the stability of partially coalesced structures ensured by interfacial jamming. Micropipette aspiration and flow in tapered capillaries experiments reveal intriguing reversible and nonreversible modes of mechanical deformation, respectively. The mechanical robustness of the microcapsules and the ability to engineer their shape and to design highly specific binding responses through protein engineering suggest that these microcapsules may be useful for biomedical applications. | 10.1021/acs.langmuir.7b03226 |
pubmed_1004_2564 | BACKGROUND
Proprotein convertase subtilisin kexin-like 9 (PCSK9) is a secreted glycoprotein that is transcriptionally regulated by cholesterol status. It modulates levels of circulating low density lipoprotein cholesterol (LDLC) by negatively regulating low density lipoprotein receptor (LDLR) levels. PCSK9 variants that result in 'gain of function' have been linked to autosomal dominant hypercholesterolemia, while significant protection from coronary artery disease has been documented in individuals who carry 'loss of function' PCSK9 variants. PCSK9 circulates in human plasma, and we previously reported that plasma PCSK9 is positively correlated with total cholesterol and LDLC in men.
RESULTS
Herein, we report the effects of two lipid-modulating therapies, namely statins and fibrates, on PCSK9 plasma levels in human subjects. We also document their effects on endogenous PCSK9 and LDLR expression in a human hepatocyte cell line, HepG2, using immunoprecipitation and immunoblot analyses. Changes in plasma PCSK9 following fenofibrate or gemfibrozil treatments (fibric acid derivatives) were inversely correlated with changes in LDLC levels (r = -0.558, p = 0.013). Atorvastatin administration (HMGCoA reductase inhibitor) significantly increased plasma PCSK9 (7.40%, p = 0.033) and these changes were inversely correlated with changes in LDLC levels (r = -0.393, p = 0.012). Immunoblot analyses of endogenous PCSK9 and LDLR expression by HepG2 cells in response to statins and fibrates showed that LDLR is more upregulated than PCSK9 by simvastatin (2.6x vs 1.5x, respectively at 10 muM), while fenofibrate did not induce changes in either.
CONCLUSION
These results suggest that in vivo (1) statins directly increase PCSK9 expression while (2) fibrates affect PCSK9 expression indirectly through its modulation of cholesterol levels and (3) that these therapies could be improved by combination with a PCSK9 inhibitor, constituting a novel hypercholesterolemic therapy, since PCSK9 was significantly upregulated by both treatments. | 10.1186/1476-511X-7-22 |
pubmed_385_11903 | The formation of the insecticide methidathion (S-[(5-methoxy-2-oxo-1,3,4-thiadiazol-3(2H)-yl)methyl] O,O-dimethyl phosphorodithioate) complexes with inorganic cation-saturated (Mg2+, Ca2+, Cu2+, and Ni2+) montmorillonites was investigated. The nature and structure of the complexes was determined by X-ray diffraction and infrared spectroscopy. The arrangement of the pesticide molecule in the interlayer space was also considered from ab initio calculations using simpler related molecules. The insecticide methidathion penetrated the interlayer spaces of the homoionic clay samples. The ligand-cation interactions in these complexes depend on the nature and characteristics of the saturating cations. Mechanisms involving water bridges and direct coordination with the exchange cation were proposed for the adsorption of methidathion by inorganic cation-saturated montmorillonites. The effect of the inorganic cations on the sorption of the cationic surfactant tetradecyltrimethylammonium bromide (TDTMA) by montmorillonite was also studied and the subsequent sorption of methidathion in TDTMA+-Montmorillonite determined. Van der Waals bonds constitute the methidathion adsorption mechanism by montmorillonite saturated with TDTMA+. The arrangements of methidathion and of the cationic surfactant molecules in the montmorillonite interlayer space were demonstrated. | 10.1081/pfc-200026781 |
pubmed_364_15196 | Over the years, an amount of models relying on effective parameters were implemented in the challenging issue of the topside ionosphere description. These models are based on different analytical functions, but all of them depend on a parameter called effective scale height, that is deduced from topside electron density measurements. As their names state, they are effective in reproducing the topside electron density profile only when applied to the analytical function used to derive them. Then, in principle, they do not have any physical meaning. It is the goal of this paper to mathematically link the effective scale height modeled through the Epstein layer to the vertical scale height theoretically deduced from the plasma ambipolar diffusion theory. Firstly, effective and theoretical scale heights are linked through a mathematical relation by showing that they tend to each other in the topside ionosphere. Secondly, their connection is preliminarily demonstrated by calculating effective scale height values from the entire COSMIC/FORMOSAT-3 radio occultation dataset. Thirdly, a possible connection between the vertical gradient of the topside scale height (as obtained by COSMIC/FORMOSAT-3 satellites) and the electron temperature (as obtained by ESA Swarm B satellite) is studied by highlighting corresponding similarities in the diurnal, seasonal, solar activity, and latitudinal variability. | 10.1038/s41598-020-73886-4 |
pubmed_86_16042 | In the present study, stromal vascular cells were obtained from the inguinal fat pad of 3-day-old rats and layered on a continuous density gradient (Percoll). After centrifugation, it was possible to collect three homogeneous cell populations of different densities and to grow them separately in primary culture. Upon reaching a confluent state two of them particularly (the lighter fractions) converted to adipocytes with a high frequency (90 per cent) in the presence of physiological concentration of insulin (10(-8) M). During the adipose conversion insulin markedly enhanced the activities of lipogenic enzymes. When VLDL (350 micrograms lipids/ml) and heparin (10 IU/ml) were added to the medium, this effect was not potentiated. However VLDL and heparin in presence of insulin increased the triacylglycerol content of the differentiated cells. The heavier fraction did not undergo adipose conversion to the same extent as the lighter ones. It was concluded that the high ability of these precursor cells to convert to adipocytes and their response to low concentration of insulin could be related to the early development stage of the tissue. | pubmed_86_16042 |
pubmed_788_14901 | BACKGROUND
A 3(1/2)-year-old girl with Stage 4 neuroblastoma received multiple blood components and was subsequently diagnosed with Chagas disease, which is caused by Trypanosoma cruzi.
STUDY DESIGN AND METHODS
All blood donors of the units that were transfused were requested to return to the collection facility for a blood sample to be tested for antibodies to T. cruzi.
RESULTS
One first-time donor was found to be positive for the presence of T. cruzi antibodies. This donor was originally from Bolivia and immigrated to the United States 17 years previously. She had not returned to her native country since her emigration.
CONCLUSIONS
This is the seventh reported case of Chagas disease transmission by blood transfusion in the United States and Canada. Although this would not be expected to occur in New England, it did, and this case demonstrates the significance of the immune status of patients as it relates to transfusion-acquired infections, the impact of geographic mobility in disease transmission, and the need for a licensed screening test for Chagas disease for the US blood supply. | 10.1111/j.1537-2995.2006.01147.x |
pubmed_175_11621 | BACKGROUND
Accurate measurement of pain is required to improve its management and in research. The visual analog scale (VAS) on paper format has been shown to be an accurate, valid, reliable, and reproducible way to measure pain intensity. However, some limitations should be considered, some of which can be implemented with the introduction of an electronic VAS version, suitable to be used both in a tablet and a smartphone.
OBJECTIVE
This study aimed to validate a new method of recording pain level by comparing the traditional paper VAS with the pain level module on the newly designed Interactive Clinics app.
METHODS
A prospective observational cross-sectional study was designed. The sample consisted of 102 participants aged 18 to 65 years. A Force Dial FDK 20 algometer (Wagner Instruments) was employed to induce mild pressure symptoms on the participants' thumbs. Pain was measured using a paper VAS (10 cm line) and the app.
RESULTS
Intermethod reliability estimated by ICC(3,1) was 0.86 with a 95% confidence interval of 0.81 to 0.90, indicating good reliability. Intramethod reliability estimated by ICCa(3,1) was 0.86 with a 95% confidence interval of 0.81 to 0.90, also indicating good reliability. Bland-Altman analysis showed a difference of 0.175 (0.49), and limits of agreement ranged from -0.79 to 1.14.
CONCLUSIONS
The pain level module on the app is highly reliable and interchangeable with the paper VAS version. This tool could potentially help clinicians and researchers precisely assess pain in a simple, economic way with the use of a ubiquitous technology. | 10.2196/13468 |
pubmed_848_15589 | The author introduces the 15th Annual Symposium on Basic Physics. In the first of this series of tutorials on the physics of mammography, the basic radiologic physics principles applied in radiographic imaging equipment are discussed in terms of a mammographic system. The analysis is intended to assist in the understanding of mammography in particular and radiography in general. Mammographic systems differ from those of general radiography in several important details because of the differing clinical demands. | 10.1148/radiographics.10.1.2296682 |
pubmed_433_23251 | OBJECTIVE
To evaluate the utility of the chemiluminescent enzyme immunoassay (CLEIA) method for point-of-care (POC) measurement of canine plasma thrombin-antithrombin complex (TAT) concentration.
ASSESSMENT AND MAIN RESULTS
Plasma TAT concentration was measured in 54 healthy dogs and in 72 dogs with various diseases. A significant correlation was found between TAT concentration measured by CLEIA and that measured by an ELISA that was previously used in dogs. The upper limit of the reference value of TAT concentrations measured by CLEIA was determined to be 0.2 ng/mL based on the TAT concentration in 54 healthy dogs. TAT concentrations exceeded the reference interval in a portion of dogs when a hypercoagulable state may be present.
CONCLUSIONS
Canine plasma TAT concentrations measured using CLEIA were correlated with that measured using ELISA. Hence, a POC testing instrument may be used for early detection of activation of thrombin generation in emergency and critical care settings. | 10.1111/vec.12913 |
pubmed_259_6366 | Until recently, echovirus 13 has been a very rare cause of aseptic meningitis. We investigated an outbreak of echovirus 13 in central Israel during the summer of 2000 using a prospective case control study and a retrospective study. Echovirus 13 was isolated from 79 cerebrospinal fluid (CSF) specimens from different medical centres in central Israel. Patients' ages ranged from 10 days to 41 years (95% < 15 years, M/F ratio 62/38). A total of 128 patients with clinical aseptic meningitis were admitted to the Department of Pediatrics during the outbreak (aged 10 days to 18 years, mean 5.4 years), and 58 CSF samples were processed for viral cultures. Thirty of them did not grow any virus, 26 samples yielded echovirus 13, and 2 samples echovirus 7. The clinical features of patients with echovirus 13 in the CSF were similar to those in whom no virus was isolated or those infected with other enteroviral strains except for higher rate of fever on admission, and prolonged time with fever following the diagnosis in the echovirus 13 patients. CSF cell count varied from 4 to 2,333 cells/mm3 with polymorphonuclears (PMN) predominant in 90% of our patients. In a case-control study there was no significant difference between patients and matched controls with regard to parameters such as: day care attendance, recreation in summer camp, swimming pools and at the beach, and consumption of tap water. All the patients in our series recovered fully with no neurological abnormalities. The illness caused by echovirus 13 was benign and involved mainly patients younger than 15 year of age. Several features that characterized this outbreak include relatively high WBC in the blood and a minent CSF PMN response. | 10.1017/s095026880200818x |
pubmed_614_22739 | Most pathogenic, non-O1/non-O139 serogroup Vibrio cholerae strains cause diarrheal disease in the absence of cholera toxin. Instead, many use Type 3 Secretion System (T3SS) mediated mechanisms to disrupt host cell homeostasis. We identified a T3SS effector protein, VopX, which is translocated into mammalian cells during in vitro co-culture. In a S. cerevisiae model system, we found that expression of VopX resulted in a severe growth defect that was partially suppressed by a deletion of RLM1, encoding the terminal transcriptional regulator of the Cell Wall Integrity MAP kinase (CWI) regulated pathway. Growth of yeast cells in the presence of sorbitol also suppressed the defect, supporting a role for VopX in destabilizing the cell wall. Expression of VopX activated expression of β-galactosidase from an RLM1-reponsive element reporter fusion, but failed to do so in cells lacking MAP kinases upstream of Rlm1. The results suggest that VopX inhibits cell growth by stimulating the CWI pathway through Rlm1. Rlm1 is an ortholog of mammalian MEF2 transcription factors that are proposed to regulate cell differentiation, proliferation, and apoptosis. The collective findings suggest that VopX contributes to disease by activating MAP kinase cascades that elicit changes in cellular transcriptional programs. | 10.3390/toxins7104099 |
pubmed_873_16743 | To prevent and treat Parkinson's disease in its early stages, it is essential to be able to detect the degree of early dopaminergic neuron degeneration. Dopamine transporters (DAT) in the striatum regulate synaptic dopamine levels, and striatal 99mTc-TRODAT-1 single-photon emission computed tomography (-SPECT) imaging is a marker for presynaptic neuronal degeneration. However, the association between the degree of dopaminergic degeneration and in vivo 99mTc-TRODAT-1 SPECT imaging is unknown. Therefore, this study investigated the association between the degree of 6-hydroxydopamine (6-OHDA)-induced dopaminergic degeneration and DAT imaging using 99mTc-TRODAT-1 SPECT in rats. Different degrees of nigrostriatal dopamine depletion were generated by injecting different doses of 6-OHDA (2, 4, and 8 μg) into the right medial forebrain bundle. The degree of nigrostriatal dopaminergic neuron degeneration was assessed by rotational behavior and immunohistochemical staining. The results showed that striatal 99mTc-TRODAT-1 binding was significantly diminished both in the ipsilateral and the contralateral sides in the 4 and 8 μg 6-OHDA groups, and that DAT 99mTc-TRODAT-1 binding in the ipsilateral striatum showed a high correlation to apomorphine-induced rotations at 8 weeks post-lesion (r = -0.887, P < 0.01). There were significant correlations between DAT 99mTc-TRODAT-1 binding in the ipsilateral striatum and the amount of tyrosine hydroxylase immunoreactive neurons in the ipsilateral substantia nigra in the 2, 4, and 8 μg 6-OHDA groups at 8 weeks post-lesion (r = 0.899, P < 0.01). These findings indicate that striatal DAT imaging using 99mTc-TRODAT-1 is a useful technique for evaluating the severity of dopaminergic degeneration. | 10.4103/1673-5374.235077 |
pubmed_584_6045 | Profile matching methods are commonly used in searches in protein sequence databases to detect evolutionary relationships. We describe here a sensitive protocol, which detects remote similarities by searching in a specialized database of sequences belonging to a fold. We have assessed this protocol by exploring the relationships we detect among sequences known to belong to specific folds. We find that searches within sequences adopting a fold are more effective in detecting remote similarities and evolutionary connections than searches in a database of all sequences. We also discuss the implications of using this strategy to link sequence and structure space. | 10.1016/s0014-5793(03)00929-3 |
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