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pubmed_515_16442
Klotho is a senescence suppressor protein that, when overexpressed, extends the lifespan of mice. Klotho-disrupted mice exhibit atherosclerosis and endothelial dysfunction, which led us to investigate the effect of the Klotho protein on vascular inflammation, particularly adhesion molecule expression. In this study, human umbilical vein endothelial cells (HUVECs) were preincubated with Klotho protein and then exposed to tumor necrosis factor-alpha (TNF-alpha) or vehicle. Reverse transcription-PCR and Western blot analyses revealed that Klotho suppressed TNF-alpha-induced expression of intracellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). NF-kappaB activation, IkappaB phosphorylation induced by TNF-alpha were also attenuated by Klotho protein administration. The inhibition of eNOS phosphorylation by TNF-alpha was reversed by Klotho. Furthermore, Klotho inhibited TNF-alpha-induced monocyte adhesion to HUVECs and suppressed adhesion molecule expression in an organ culture of the rat aorta. These results suggest that Klotho suppresses TNF-alpha-induced expression of adhesion molecules and NF-kappaB activation. Klotho may have a role in the modulation of endothelial inflammation.
10.1007/s12020-009-9181-3
pubmed_12_7375
The currently favored theory of pathogenesis of malignant hyperthermia (MH) implicates an abnormality in skeletal muscle calcium ion transport. During a MH crisis a profound lactic acidosis occurs and in MH-sensitive individuals a delayed recovery of venous lactate has been previously noted postexercise. We have used 31P magnetic resonance spectroscopy to follow noninvasively in vivo changes in muscle of intracellular pH and high-energy phosphate metabolites during rest, exercise, and recovery of MH-sensitive subjects. Eleven biopsy-positive MH-sensitive patients have been studied and compared to 26 normal subjects. The MH-sensitive subjects as a group prematurely dropped their intracellular pH during mild aerobic exercise and they demonstrated a marked delay before the recovery of pH after maximal exercise. PCr/(PCr + Pi) ratios also dropped early during exercise but recovered normally. The observed changes in pH and PCr/(PCr + Pi) are consistent with a myopathy in MH-susceptible individuals.
10.1002/mrm.1910150109
pubmed_1017_10419
Plasmonic nanostructures, which are used to generate surface plasmon polaritons (SPPs), always involve sharp corners where the charges can accumulate. This can result in strong localized electromagnetic fields at the metallic corners, forming the hot spots. The influence of the hot spots on the propagating SPPs are investigated theoretically and experimentally in a metallic slit structure. It is found that the electromagnetic fields radiated from the hot spots, termed as the hot spot cylindrical wave (HSCW), can greatly manipulate the SPP launching in the slit structure. The physical mechanism behind the manipulation of the SPP launching with the HSCW is explicated by a semi-analytic model. By using the HSCW, unidirectional SPP launching is experimentally realized in an ultra-small metallic step-slit structure. The HSCW bridges the localized surface plasmons and the propagating surface plasmons in an integrated platform and thus may pave a new route to the design of plasmonic devices and circuits.
10.1088/0957-4484/27/38/385204
pubmed_1032_5551
Miniature inverted-repeat transposable elements (MITEs) are structurally homogeneous non-autonomous DNA transposons with high copy numbers that play important roles in genome evolution and diversification. Here, we analyzed the rice high-tillering dwarf (htd) mutant in an advanced backcross population between cultivated and wild rice, and identified an active MITE named miniature Jing (mJing). The mJing element belongs to the PIF/Harbinger superfamily. japonica rice var. Nipponbare and indica var. 93-11 harbor 72 and 79 mJing family members, respectively, have undergone multiple rounds of amplification bursts during the evolution of Asian cultivated rice (Oryza sativa L.). A heterologous transposition experiment in Arabidopsis thaliana indicated that the autonomous element Jing is likely to have provides the transposase needed for mJing mobilization. We identified 297 mJing insertion sites and their presence/absence polymorphism among 71 rice samples through targeted high-throughput sequencing. The results showed that the copy number of mJing varies dramatically among Asian cultivated rice (O. sativa), its wild ancestor (O. rufipogon), and African cultivated rice (O. glaberrima) and that some mJing insertions are subject to directional selection. These findings suggest that the amplification and removal of mJing elements have played an important role in rice genome evolution and species diversification.
10.1111/tpj.14260
pubmed_601_19044
We cloned a 12.3-kilobase (kb) endogenous plasmid, Ddp1, found in several wild-type and laboratory strains of Dictyostelium discoideum into pBR322. The cloned plasmids have been used to cotransform D. discoideum cells with B10S, a transformation vector carrying a gene fusion conferring resistance to G418. Whereas B10S DNA alone appears to integrate in a tandem array, the cloned Ddp1 plasmids replicate extrachromosomally and are stably maintained in the absence of selection with an average copy number of 50 to 100 copies per cell. The Ddp1-derived plasmids can be directly recovered by transforming Escherichia coli with bulk nuclear DNA from these cells. Preliminary deletion analysis indicates that not all regions of Ddp1 are necessary for stable replication in D. discoideum. Several recombinant vectors which replicate extrachromosomally in D. discoideum were also isolated. One contains the Act6-neor gene fusion from B10S recombined into one of the cloned derivatives of Ddp1 and can be used to directly transform D. discoideum amoebae, selecting for G418 resistance. Another recombinant is only 5.6 kb and resulted from a deletion of a 16.6-kb cloned Ddp1 hybrid plasmid. An analysis of the vector DNAs present in clones derived from single D. discoideum transformants is also described.
10.1128/mcb.5.11.3241-3250.1985
pubmed_819_2950
The prolactin receptor (PRL-R), a member of the hematopoietin cytokine receptor superfamily, is widely distributed among mammalian tissues. To understand better the potential sites of action and onset of potential PRL responsiveness, the developmental distribution pattern of PRL-R mRNA expression in fetal and neonatal mice was examined. Fetal mouse tissues were collected at distinct stages from timed pregnancies. Following extraction of total RNA, onset of gene expression was evaluated via reverse transcription-polymerase chain reaction (RT-PCR) and Southern hybridization was employed for verification. Expression of PRL-R mRNA was first observed on day 14 in the liver and cranium and on day 15 in the kidney, lung and thymus gland. Pituitary and adrenal glands were positive for PRL-R at day 18 of gestation through to day 1 of postnatal life. Neither whole fetuses prior to day 14 (days 10-13) of gestation nor skin and bladder tissues from 2-day-old mice generated detectable RT-PCR signals for PRL-R. The presence of PRL-R mRNA in fetal thymus and spleen tissues suggests a possible role for PRL in the development of the immune system. Prolactin may act directly on the pituitary to influence its own secretion and/or that of other pituitary-derived factors, as evidenced by the presence of PRL-R mRNA in the pituitary glands of fetal and 1-day-old mice. These data are the first to show the presence of PRL-R gene expression in various organ systems in fetal mice and suggest that PRL is among several factors necessary to coordinate developmental activities.
10.1530/eje.0.1340751
pubmed_667_3154
We report two male siblings with cryptophthalmos syndrome (Fraser syndrome), an autosomal recessive multiple malformation syndrome with cryptophthalmos, abnormal genitalia, and syndactyly of the fingers and toes as major clinical symptoms. Renal anomalies (uni- or bilateral agenesis) occur in 85 per cent. In the second trimester of both pregnancies (at 23.5 and 18.5 weeks, respectively), echographic examination revealed multiple anomalies: oligoamnios sequence and fetal hydrops with nuchal oedema. Contrasting with the oligohydramnios, the lungs were voluminous and hyperechogenic. Fetopathological examination revealed that the oligoamnios sequence was due to major renal abnormalities (bilateral renal agenesis in the first, and unilateral renal agenesis and contralateral multicystic renal dysplasia in the second sibling). Laryngeal substenosis had resulted in another malformation sequence consisting of overdistended lungs, and non-immune fetal hydrops. The present experience shows that in the presence of an oligoamnios sequence with contrastingly voluminous, hyperechogenic lungs, the diagnosis of cryptophthalmos syndrome should seriously be considered in the differential diagnosis.
10.1002/(sici)1097-0223(199706)17:6<582::aid-pd107>3.0.co;2-y
pubmed_271_24889
Blunt traumatic abdominal wall disruptions associated with evisceration are very rare. The authors describe a case of traumatic abdominal wall disruption with bowel evisceration that occurred after a middle-aged woman sustained direct focal blunt force impact to the lower abdomen. Abdominal exploration and surgical repair of the abdominal wall defect were performed, with good clinical outcome. A brief overview of literature pertinent to this rare trauma scenario is presented.
10.4103/2229-5151.84807
pubmed_872_12552
OBJECTIVE To report on the prenatal ultrasound findings associated with complete trisomy 9. METHODS Cases of complete trisomy 9 diagnosed prenatally were identified by reviewing the reports from two large cytogenetics laboratories serving tertiary referral centers for prenatal diagnosis. Information on prenatal ultrasound findings and outcome was obtained in all cases. RESULTS Nine cases of complete trisomy 9 were identified. The diagnosis was made in the first trimester in four cases, in the second trimester in three and in the third trimester in two. Two fetuses underwent first-trimester ultrasound screening for aneuploidy and the nuchal translucency thickness was increased in both. All five fetuses detected in the second and third trimesters had several fetal anomalies including Dandy-Walker malformation in four cases, facial dysmorphism in four, genitourinary anomalies in three, congenital heart defects in three, ventriculomegaly in three, abnormal hands in two and megacisterna magna in one. Four fetuses were growth-restricted at the time of ultrasound evaluation. However, the two cases diagnosed in the third trimester had routine second-trimester anomaly scans reported as normal. There were no survivors in this series. CONCLUSION Fetuses with complete trisomy 9 have multiple anomalies that can be readily detected prenatally by ultrasound. These mainly include, but are not restricted to, craniofacial, cardiovascular, musculoskeletal and genitourinary malformations. However, findings can be subtle and therefore missed at the routine second-trimester scan.
10.1002/uog.233
pubmed_269_18949
This study aimed to assess the developed nonwoven inserts with aerogel/PCM (phase change material) microcapsules for use in protective clothing against cold in terms of properties related to thermophysiological comfort. These inserts were obtained by the thermal bonding of a multilayer system consisting of needled-punched nonwovens and silica aerogel particles and/or PCM microcapsules evenly distributed between them. The influence of aerogel and PCM microcapsules on the basic physical properties of inserts, their microstructure, air permeability, and water vapor resistance was investigated and analyzed. The thermal insulation properties of inserts were assessed based on thermal conductivity results. The inserts with PCMs were also tested for their ability to regulate the temperature in the undergarment microclimate using the differential scanning calorimeter (DSC) and the "skin model" device. The research showed that the use of aerogel allowed for reducing the thermal conductivity of the insert by approximately 13% compared to the insert without additives. The high values obtained of the melting and crystallization enthalpy of inserts with PCMs confirmed their high efficiency in the heat absorption and release. Thus, the use of aerogel and PCMs in protective clothing against cold seems to be an effective solution for improving its protective properties and actively adapting its thermal insulation to the changing temperature conditions and the activity level of employees.
10.3390/ma15062307
pubmed_74_10751
We developed an antimicrobial air filter using natural sea salt (NSS) particles. Airborne NSS particles were produced via an aerosol process and were continuously coated onto the surface of an air filter under various deposition times. The filtration efficiency and bactericidal performance of the NSS-coated filter against aerosolized bacterial particles (Staphylococcus epidermidis, Escherichia coli) were evaluated quantitatively. The filtration efficiency of the tested filter ranged from 95% to 99% depending on the deposition time, and the bactericidal performance demonstrated efficiencies of more than 98% against both tested bacterial bioaerosols when the NSS deposition ratio was more than 500 μg/cm2. The experimental results indicated that the NSS-coated filters have the potential to be used as effective antimicrobial air filters for decreasing environmental exposure to microbial contaminants.
10.3390/ijerph17010190
pubmed_422_19630
A right ventricular outflow tract was partially obstructed by a metastatic tumor from a hepatocellular carcinoma. This tumor was treated via chemoembolization of the right coronary artery, which resulted in tumor regression and improvement of the patient's symptoms.
10.1378/chest.117.1.287
pubmed_307_21906
We obtained a full-length cDNA encoding a carboxylesterase in Sesamia nonagrioides. The complete cDNA sequence is comprised of 1838 bp with an open reading frame encoding 576 amino acid residues with predicted molecular mass of 64.24 kDa. The deduced amino acid sequence showed high identity to JHE-Related of Trichoplusia ni (65% amino acid identity) and 49-46% amino acid identity to JHEs of other lepidopterans and contained all five functional motifs of insect JHEs. The gene has been termed as SnJHE-Related (SnJHER) to denote its similarity to other insect JHE genes and the occurrence of an unusual cysteine residue immediately adjacent to the catalytic serine, instead of the conventional alanine residue. Phylogenetic analyses localised SnJHER together with TnJHER in a branch of the lepidopteran's JHEs group, with other carboxylesterases (COEs) occuring in separated groups. The JH analog methoprene did not affect the expression of SnJHER in contrast to other insect JHEs. Additionally, ecdysteroid analogs induced SnJHER gene expression. The SnJHER mRNA levels were higher in long-day non-diapausing larvae than in short-day diapausing ones. In the fifth instar of non-diapausing and ninth instar of diapausing larvae, the SnJHER mRNAs reached higher expression levels on the days close to each larval molt. In the last (sixth) non-diapausing larval instar, SnJHER mRNA levels peaked in the intermolt period but were lower than during the fifth instar.
10.1016/j.jinsphys.2011.04.017
pubmed_791_10991
A 58-year-old female with a history of recurrent pneumonia was evaluated for fevers, right lower back pain, and hematuria. A noncontrast abdominal computed tomography (CT) scan showed air and fluid-filled area in the right lower lobe for which a contrast-enhanced CT chest was performed. The CT of the chest revealed the cystic mass was supplied by an anomalous artery from the descending aorta. The patient was then diagnosed with a superinfected bronchopulmonary sequestration which was treated with surgical resection.
10.4103/lungindia.lungindia_73_20
pubmed_374_7941
BACKGROUND Direct-acting antivirals (DAA) have revolutionized hepatitis C treatment, with high sustained virological response (SVR) rates reported, even in historically difficult-to-treat groups. SVR is associated with a decreased risk of hepatocellular carcinoma (HCC), need for transplantation, and overall and liver-related mortality. Data from real-life cohorts on the medium- to long-term outcomes of patients with advanced liver disease and DAA-induced SVR are still missing. OBJECTIVES To report and analyze the long-term outcomes of DAA-induced SVR in a real-life cohort of patients with advanced liver disease. METHOD In this retrospective, longitudinal, single-center study, we collected data from patients with chronic hepatitis C infection and advanced liver disease (cirrhosis or advanced fibrosis) that had initiated DAA treatment between February 2015 and January 2017. RESULTS A total of 237 patients were included. A treatment completion rate of 98.7% and an SVR rate of 97.8% (intention to treat: 96.6%) were found. Of the 229 patients with SVR, 67.2% were cirrhotic (64.2% Child-Pugh class A; 3.1% Child-Pugh class B) and 32.8% had stage F3 fibrosis, with an average follow-up of 28 months. The overall mortality rate was 19/1,000 person-years and the liver-related mortality rate was 9.5/1,000 person-years. The hepatic decompensation incidence rate was 25/1,000 person-years and the HCC incidence rate was 11.6/1,000 person-years. There was a sustained increase in serum platelet values during up to 2 years of follow-up. A history of pretreatment decompensation and baseline platelet and albumin values were significantly associated with the occurrence of adverse liver events after the end of treatment. CONCLUSIONS A DAA-induced SVR remains durable and is associated with an excellent clinical prognosis in patients with compensated advanced liver disease and with improvement or disease stabilization in decompensated patients. SVR is associated with a low risk of - yet does not prevent - HCC occurrence or disease progression, especially in the presence of other causes of liver injury. It is recommended that these patients be kept under surveillance.
10.1159/000503074
pubmed_792_4733
Calcium phosphate ceramics are used in the substitution of injured or damaged bones. Nevertheless, the behaviour of these materials, and in particular, the mechanisms guiding their interface response in physiological environment is still unknown. This work describes the construction of hydroxyapatite and tricalcium phosphate electrodes used to determine the interface potential behaviour of these materials in a simulated body fluid, in a pH range corresponding to the variation observed in human body injuries, at ambient and physiological temperatures. These measurements are associated with the adsorption/desorption of ions from the materials. The results show that hydroxyapatite and tricalcium phosphate have similar behaviour in that they reach an interface potential equilibrium state faster when the solution pH is decreased and the temperature increased. This behaviour may be attributed to their ability to form a calcium-rich layer and is relevant to their quality as implantable materials.
10.1016/s0142-9612(98)00148-3
pubmed_335_23654
Swimming results in significant and repetitive stress on the hip as well as other joints, and hip pain in swimmers should not be ignored. Stretching and strengthening are the mainstays of injury prevention, and recent literature supports that when indicated, femoroacetabular impingement surgical treatment in swimmers results in excellent outcomes including return to sport and frequently at a level of performance superior to pre-injury status.
10.1016/j.arthro.2018.01.032
pubmed_889_1841
Interferometry is an optical technique that have been used to quantify the lipid layer of the precorneal tear film, and to investigate the relationship between lipid layer thickness and tear film evaporation. However, the relationship between lipid layer thickness and the rate of evaporation is far from consistent. One possible reason is the inherent limit of contemporary interferometric systems, which employ objectives with relatively long depth of focus (DOF) (>15 μm or more), which tend to collect excessive extra-planar noise. This limitation may negatively affect the accuracy of the characterization and thickness measurement of the lipid layer. The current system incorporated an objective with limited DOF (∼1.5 μm) into a custom-built optical microscope to image the tear film lipid layer in humans. An algorithm was also developed to process these images. One major outcome of this system is that thick lipid layers exhibit higher variation in thickness values than thin or normal-thickness lipid layers. The variations may reflect the structural differences of the lipid layer, which may offer a novel dimension to explain the missing correlation between lipid layer thickness and evaporation. In summary, the development of the high resolution microscopy system and associated data processing algorithm may provide new insights into the lipid layer structure, topography and their relation to the tear film evaporation rate.
10.1016/j.jtos.2018.12.003
pubmed_428_20995
The present study aimed to examine the putative preventive effect of the ethanolic extract Date Palm Pollen (DPP, Phoenix dactylifera L., family Arecaceae) on isoproterenol-induced myocardial infarction (MI) in rats. Twenty four rats were randomly divided into four groups including control. They were treated with DPP extract (400mg/kg) and clopidogrel (0.2mg/kg) for 7days followed by myocardial injury induction using subcutaneous isoproterenol (100mg/kg) with an interval of 24h for two days (6th and 7th day). Administration of isoproterenol exhibited indicative changes in the ECG pattern evidenced by significant elevation of ST-segment and cardiac injury markers viz.; troponin-T, creatine phosphokinase (CPK), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) by 315%, 71%, 64% and 170%, respectively as compared to control. Additionally, the angiotensin-converting enzyme (ACE) activity in plasma was increased by 33% associated to histological myocardial necrosis. However, pre-co-treatment with DPP extract improved the cardiac biomarkers injury, normalized cardiac function indices and prevented the ventricular remodeling process through inhibition of ACE activity by 34% and the inhibition of the generation of radical oxygen species. Extensive characterization of this DPP extract using LC-HRMS revealed numerous flavonoids and phenols compounds which could be endowed with cardiopreventive actions. Overall, these results proved that DPP extract has preventive effects on cardiac remodeling process.
10.1016/j.etp.2017.06.004
pubmed_541_17452
Detection and recognition of point-light walking is reduced when the display is inverted, or turned upside down. This indicates that past experience influences biological motion perception. The effect could be the result of either presenting the human form in a novel orientation or presenting the event of walking in a novel orientation, as the two are confounded in the case of walking on feet. This study teased apart the effects of object and event orientation by examining detection accuracy for upright and inverted displays of a point-light figure walking on his hands. Detection of this walker was greater in the upright display, which had a familiar event orientation and an unfamiliar object orientation, than in the inverted display, which had a familiar object orientation and an unfamiliar event orientation. This finding supports accounts of event perception and recognition that are based on spatiotemporal patterns of motion associated with the dynamics of an event.
10.1111/1467-9280.24471
pubmed_68_13328
The nm23-H1 gene is regarded as a human homologue of the mouse nm23 gene, which was expressed in a non-metastatic subline of mouse melanoma K-1735. The expression levels of nm23-H1 mRNA and the levels of protein during induced differentiation of human leukemia cell lines were analysed. mRNA levels of the megakaryoblastic leukemia line MEG-01, which were induced to differentiate into megakaryocyte by TPA, decreased rapidly from 2 days after the start of treatment and became almost undetectable at day 4. Similar down-regulation of nm23-H1 mRNA was also observed in the induced differentiation of the promyelocytic leukemia line HL-60 by TPA, or DMSO into monocyte-macrophage lineage or granulocytes, respectively. The amount of Nm23-H1 protein was analysed by Western immuno-blot analysis using mouse antiserum raised against a recombinant fusion protein with glutathione S-transferase. The amount of Nm23-H1 protein also decreased during the induced differentiation of these leukemia cell lines. On the other hand, in the differentiation of the erythroleukemia line K562 by hemin, levels of both mRNA and protein of Nm23-H1 elevated transiently, then reduced to the original level. When MEG-01 and K562 were stably transfected with nm23-H1 cDNA, MEG-01 transfectants showed reduced sensitivity to the induction of differentiation, whereas K562 transfectants were better induced to synthesize hemoglobin than controls. These findings suggest the possibility that Nm23-H1 protein plays an important role to maintain the proliferation of immature leukemic cells in MEG-01 and HL-60, but it may also play a role in the early stage of K562 differentiation, possibly in the different manner.
pubmed_68_13328
pubmed_861_10764
Gas sensor arrays, also called electronic noses, use many chemically diverse materials to adsorb and subsequently identify gas species in complex mixture environments. Ideally these materials should have maximally complementary adsorption profiles to achieve the best sensing performance, but in practice they are selected by trial-and-error. Thus current electronic noses do not achieve optimal detection. In this work, we employ metal-organic frameworks (MOFs) as sensing materials and leverage a genetic algorithm to identify optimal combinations of them for detecting methane leaks in air. We build on our previously reported computational design methodology, which ranked MOF arrays by their Kullback-Liebler divergence (KLD) values for probabilistically describing the concentrations of each gas species in an unknown mixture. We ran the genetic algorithm to find optimal MOF arrays of various sizes when selecting from a library of 50 different MOF materials. The genetic algorithm was able to accurately predict the best arrays of any desired size when compared to brute-force screening. Thus, this search optimization can be integrated into the efficient design of MOF-based electronic noses.
10.1021/acssensors.9b00268
pubmed_476_25032
INTRODUCTION Hepatitis B is a potentially life-threatening liver infection caused by hepatitis B virus (HBV) and China has the largest disease burden. We aim to understand the ethnic disparities in HBV infection among the married reproductive-age couples planning for pregnancy in Yunnan, a multiethnic province in Southwest China, to increase the health equities within the hepatitis response in China. METHODS A population-based cross-sectional study was performed. Couples aged 20-49 years in rural Yunnan were enrolled through the National Free Preconception Health Examination Project from Jan 2014 to Dec 2019. HBsAg-positive couples were defined as couples in which one or both were HBsAg-positive, and HBsAg- and HBeAg-positive couples were defined as couples in which one or both were HBsAg- and HBeAg-positive. The HBV prevalence of positive couples was estimated by ethnicity. Multivariate logistic regression analyses were used to assess the association between ethnicity and HBsAg status. RESULTS Overall, 63,513 of 1,060,643 couples (5.99%, 95% CI, 5.94%-6.03%) were HBsAg-positive, and 15,898 of 63,513 HBsAg-positive couples (25.03%, 95% CI 24.69%-25.37%) were HBsAg- and HBeAg-positive couples in rural Yunnan. The highest prevalence of HBsAg-positive couples was in the Miao and Miao ethnicity (12.04%) and Zhuang and Zhuang ethnicity (9.76%), and the risk of HBV infection of wives/husbands in these ethnic groups was significantly higher than that in the Han and Han ethnicity. Additionally, the HBsAg prevalence in wives/husbands has increased with the positive status of HBsAg and HBeAg of their spouses. CONCLUSION The HBV prevalence in reproductive-age couples was intermediate (6% of 1 million couples) in rural Yunnan, China, with the highest in the Miao and Zhuang ethnicities. There are still large ethnic disparities in HBV infection in China. Therefore, China should make great efforts, especially giving priority to ethnic minorities and taking positive couples as an important unit of care, to equitably eliminate the HBV intrafamilial transmission.
10.3389/fmed.2021.799873
pubmed_254_1065
PURPOSE To evaluate effects of glaucoma and central corneal thickness (CCT) on optic nerve head biomechanics. METHODS Four groups were formed according to CCT measurements and the presence of glaucoma. Glaucomatous patients with thin (< 510 µ) and thick (> 570 µ) corneas composed groups 1 and 3, respectively. Nonglaucomatous patients with thin and thick corneas composed groups 2 and 4, respectively. Real-time elastography (RTE) was performed on all groups, and optic nerve strain rate (ONSR), orbital fat strain rate (OFSR), and strain ratio of orbital fat to the optic nerve and medial and lateral parts of the optic nerve (SROFON, SROFMON, SROFLON, respectively) were obtained and compared between groups. The correlations between CCT and these parameters were also investigated. RESULTS Statistically significant difference was not found between groups in terms of strain rate of optic nerve and orbital fat, SRFON, SROFMON and SROFLON. There was a positive correlation between ONSR and OFSR and mean CCT in patients with CCT thinner than 510 µ (p: 0.03 r: 0.26, p: 0.01 r: 0.32 respectively). CONCLUSION SROFON, SROFLON and SROFMON values did not differ between glaucomatous and nonglaucomatous patients with thin or thick CCTs. The correlations between CCT and OFSR and ONSR were found to be statistically significant in patients with thin CCT.
10.1007/s10792-020-01686-w
pubmed_1020_5308
Extensive metabolic remodeling is a fundamental feature of cancer cells. Although early reports attributed such remodeling to a loss of mitochondrial functions, it is now clear that mitochondria play central roles in cancer development and progression, from energy production to synthesis of macromolecules, from redox modulation to regulation of cell death. Biosynthetic pathways are also heavily affected by the metabolic rewiring, with protein synthesis dysregulation at the hearth of cellular transformation. Accumulating evidence in multiple organisms shows that the metabolic functions of mitochondria are tightly connected to protein synthesis, being assembly and activity of respiratory complexes highly dependent on de novo synthesis of their components. In turn, protein synthesis within the organelle is tightly connected with the cytosolic process. This implies an entire network of interactions and fine-tuned regulations that build up a completely under-estimated level of complexity. We are now only preliminarily beginning to reconstitute such regulatory level in human cells, and to perceive its role in diseases. Indeed, disruption or alterations of these connections trigger conditions of proteotoxic and energetic stress that could be potentially exploited for therapeutic purposes. In this review, we summarize the available literature on the coordinated regulation of mitochondrial and cytosolic mRNA translation, and their effects on the integrity of the mitochondrial proteome and functions. Finally, we highlight the potential held by this topic for future research directions and for the development of innovative therapeutic approaches.
10.3389/fonc.2021.797265
pubmed_616_11482
Phototrophic bioprocesses are a promising puzzle piece in future bioeconomy concepts but yet mostly fail for economic reasons. Besides other aspects, this is mainly attributed to the omnipresent issue of optimal light supply impeding scale-up and -down of phototrophic processes according to classic established concepts. This MiniReview examines two current trends in photobiotechnology, namely microscale cultivation and modeling and simulation. Microphotobioreactors are a valuable and promising trend with microfluidic chips and microtiter plates as predominant design concepts. Providing idealized conditions, chip systems are preferably to be used for acquiring physiological data of microalgae while microtiter plate systems are more appropriate for process parameter and medium screenings. However, these systems are far from series technology and significant improvements especially regarding flexible light supply remain crucial. Whereas microscale is less addressed by modeling and simulation so far, benchtop photobioreactor design and operation have successfully been studied using such tools. This particularly includes quantitative model-assisted understanding of mixing, mass transfer, light dispersion and particle tracing as well as their relevance for microalgal performance. The ultimate goal will be to combine physiological data from microphotobioreactors with hybrid models to integrate metabolism and reactor simulation in order to facilitate knowledge-based scale transfer of phototrophic bioprocesses.
10.1093/femsle/fnx238
pubmed_510_11348
Peripheral blood mononuclear cells from cattle experimentally infected with Babesia bovis were examined for parasite-specific cell-mediated immune responses. Unfractionated merozoites and soluble and membrane fractions derived from merozoites were all antigenic for immune cattle, although the membrane fraction was the most stimulatory. Cattle responded to different antigenic fractions in a differential manner, and only that animal immunized with autologous cultured parasites responded to parasitized erythrocyte culture supernatants. Plastic-adherent cells (presumably monocytes/macrophages) were required for a proliferative response to babesial antigens but not to the T-cell mitogen concanavalin A, suggesting that babesial proteins are not simply mitogenic for T cells. Lymphocyte responses directed against a different hemoparasite from Mexico, Babesia bigemina, indicate that this parasite shares cross-reactive T-cell epitopes with B. bovis. These studies define a system whereby T lymphocytes from babesia-immune cattle can be used in proliferation assays to identify babesial merozoite antigens which are immunogenic for T cells. Because identification of helper T-cell epitopes is important for the design of a babesial subunit vaccine which will evoke anamnestic responses, the studies described here provide a basis for such experiments.
10.1128/iai.59.7.2418-2426.1991
pubmed_516_22605
OBJECTIVES To determine the occurrence of antimicrobial resistance genes and role of integrons among 135 antimicrobial-resistant Salmonella enterica from Brazil. METHODS The presence of antimicrobial resistance genes, class 1 and 2 integrons and gene cassettes was analysed by PCR and sequencing. The genetic location of class 1 integrons was determined in 25 isolates by hybridization and plasmid transfer experiments. RESULTS Fifty-five of the isolates were positive for class 1 integrons. Integron-positive isolates represented 17 different serovars and were mainly from human (n=28) and animal (n=13) sources. The gene cassette arrangements could be determined in 51 of the positive isolates, which harboured one [dfrA22, aadA1 or orf3 (putative trimethoprim resistance)], two [aadA1-dfrA1, aac(6')-Ib-orf1 (unknown function) or aacA4-aadA1], three [dfrA15b-cmlA4-aadA2, orf2 (unknown function)-dfrA5-orfD] or four [orf4-aacA4-blaOXA-30 (interrupted by an IS1 element)-aadA1] cassettes in their variable region. Only one isolate harboured a class 2 integron with the gene cassette array dfrA1-sat-aadA1. Several integron unrelated resistance genes were also detected in the isolates. Sulphonamide resistance was primarily mediated by sul2 and sul3, tetracycline resistance by tet(B) and tet(A), chloramphenicol resistance by catA1, streptomycin resistance by strA and ampicillin resistance by blaTEM. blaCTX and blaCMY-2 were found in cephalosporin-resistant isolates. Mating and hybridization experiments demonstrated that a high-molecular-weight plasmid mediated the gene transfer of integrons and additional resistance determinants. CONCLUSIONS The present study revealed that integron-mediated resistance genes contributed to the multiresistance phenotype observed in the isolates, but most resistance genes were located outside the integron structure, as independent genes. However, they might be located on the same conjugative plasmid.
10.1093/jac/dkl248
pubmed_833_10394
MERMAID is an EU financed telemedicine project with global reach and 24-hour, multilingual capability. It aspires to provide a model for the provision of health care services based on the electronic transmission of medical information, via ISDN based videoconferencing. This model will not be limited to medical diagnostics but it will encompass all cases where the actual delivery of health care services involves a patient who is not located where the provider is. Its implementation requires the commissioning of an expensive telecommunications infrastructure and the exploration of a number of solutions. In fact, all categories of telemedical applications (audio and video conferencing, multimedia communications, flat file and image transfer with low, medium and high bandwidth data requirements) will be considered while the full range of network choices (Digital land lines, Cellular/Wireless, Satellite and Broadband) will be tested in terms of cost/performance tradeoffs that are inherent to them and the developmental stage each of these options occupies in their in its life cycle. Finally, out that MERMAID utilises advanced land based line transmission technologies to aid the remote patient by making available the specialist care that is best suited in the particular case.
pubmed_833_10394
pubmed_1098_24371
Background Bacterial resistance to antibiotics has increased in recent years. Resistance to β-lactams in Gram-negative bacteria has been reported to be associated with extended spectrum beta-lactamases and metallo-beta-lactamases. This study was aimed at determining the distribution and antibiotic susceptibility patterns of Gram-negative pathogens producing extended spectrum beta lactamases and metallo-beta lactamases. Method and Methodology. This cross-sectional study was conducted at the National Public Health Laboratory during a period of six months. All clinical specimens were obtained and processed for the identification of Gram-negative pathogens by culture, morphological, and biochemical tests. Antibiotic susceptibility testing of the isolates was performed by the Kirby Bauer disc diffusion and the isolates were tested for ESBL and MBL by the combined disk method. Results Out of 4266 clinical specimens, 197 (4.6%) were found to be Gram-negative bacterial isolates. 47 (23.9%) isolates were ESBL producers. The most predominant organisms were Escherichia coli (53%), Klebsiella pneumonia (23%), and Pseudomonas spp. (13%). 16 (8.2%) were positive for MBL producers, and 6(3.1%) were both ESBL and MBL producers. The MBL activity was seen in E. coli (38%), followed by Pseudomonas spp. (31%), and K. pneumoniae (19%). The ESBL producers showed a higher degree of sensitivity towards imipenem and amikacin, followed by piperacillin tazobactam. MBL producers showed sensitivity towards amikacin only. Conclusion The prevalence of ESBL and MBL producing Gram-negative bacteria was found to be high in bacterial infections in Nepal. Routine laboratory testing for ESBL and MBL is needed in order to optimize antibiotic management and reduce the risk of spread of infections caused by ESBL and MBL producers.
10.1155/2022/5474388
pubmed_805_15751
In order to perform an analysis of nonlinear EEG-dynamics we investigated the EEG of ten male probands during sleep. According to Rechtschaffen and Kales (1968) we scored the sleep-EEG and applied an algorithm, proposed by Grassberger and Proccaccia (1983) to compute the correlation dimension of different sleep stages. The correlation dimension characterizes the dynamics of the EEG signal and estimates the degrees of freedom of the signal under study. We could demonstrate, that the EEG of slow wave sleep stages depicts a dimensionality, which is two units smaller than that of light or REM sleep.
10.1007/BF00199594
pubmed_582_10920
OBJECTIVE The aim of this study was to assess the cellular proliferation rate of major and minor salivary gland mucoepidermoid carcinomas (MECs) by quantitative analysis of AgNOR and to determine its relation to histopathologic grading. STUDY DESIGN Thirty-five cases of major and minor salivary gland MECs, were retrieved and graded according to the AFIP grading schema. The mean AgNOR count was calculated for all cases. RESULTS Mean AgNOR counts were 0.64 +/- 0.15 in low-, 1.04 +/- 0.21 in intermediate-, and 1.42 +/- 0.23 in high-grade MECs. A significant difference was observed in the mean AgNOR counts among the 3 groups (P < .001). CONCLUSION It can be suggested that the AgNOR technique can be applied on routine histological samples to assess the growth potential of MECs. However, its prognostic value should be validated with clinical studies and survival analyses.
10.1016/j.tripleo.2007.09.002
pubmed_94_12373
Low-temperature anaerobic methane conversion to methanol (MTM) using copper ion-exchanged mordenite (Cu-MOR) as the catalyst and water as the sole source of oxygen is promising for sustainable utilization of methane. Integrating in situ calorimetric, spectroscopic, and structural methodologies, we report a systematic study on energetics of water-cationic species-framework guest-host interactions as a function of water loading for several mordenites relevant to low-temperature MTM. Notably, the near-zero coverage hydration enthalpy on Cu-MOR is -133.1 ± 6.0 kJ/mol water, which is related to Cu-MOR regeneration using water as oxidant. The copper oxo sites are thermally stable up to 915 °C and remain chemically intact as an oxygen source after complete hydration and dehydration. This study underscores the importance of manipulating the oxidation state and coordination chemistry of transition metal guest species in zeolites by fine-tuning the partial pressure of water as a strategy for rational design, synthesis, and modification of catalysts.
10.1021/acs.jpclett.0c01331
pubmed_256_11934
The outcome of surgery in the elderly depends on the skill of the surgeon and the expertise of the anaesthetist caring for the patient. This anaesthetic proficiency depends initially on the application of the detailed knowledge of the drugs used during anaesthesia, and on the understanding of the way changes in the elderly patients' physiology with ageing affects both kinetic and dynamic facets of pharmacology. However, the very diversity of the elderly population makes their precise response to drugs unpredictable, and, therefore, clear, unequivocal guidance on practice is limited. The important changes in both physiology and pharmacokinetics with ageing are discussed before covering the specific drugs used in current anaesthetic practice in the United Kingdom. This review covers the drugs used primary for the induction and maintenance of anaesthesia, and only covers related fields where there are changes in recent practice that raise issues of importance during surgery. This review, therefore, deals mainly with the anaesthetic vapours and intravenous drugs, and with neuromuscular blocking agents. The restriction of space and the enormity of the subject demand that the areas covered in this review are solely limited to the major classes of drugs used routinely in general anaesthetic practice in the United Kingdom. The detailed pharmacokinetics and pharmacodynamics of drugs also used in the post-operative period, such as the wide variety of opiates, and of drugs mainly used in general medical practice, but occasionally used as premedicants or supplements during anaesthesia, have been monitored only in passing.
10.1016/0163-7258(94)00070-j
pubmed_288_21651
Pheochromocytoma is an infrequent secondary cause of arterial hypertension, often associated with paroxysmal headache, sweating, weight loss, and palpitations. Cardiovascular complications of pheochromocytoma include sudden death, heart failure due to toxic cardiomyopathy, and hypertensive encephalopathy. Here we report the case of a female with an acquired long-QT-syndrome as a rare complication of an extra-adrenal pheochromocytoma. Diagnosis was made after sotalol-induced Torsades de Pointes.
10.1291/hypres.30.1263
pubmed_950_14827
Acrylamide polymers were widely used as oilfield chemical treatment agents because of their wide viscosity range and versatile functions. However, with the increased formation complexity, their shortcomings such as poor solubility and low resistance to temperature, salt, and calcium were gradually exposed. In this paper, acrylamide (AM)/2-acrylamide-2-methyl-1-propane sulfonic acid (AMPS) copolymers were synthesized by aqueous solution polymerization and inverse emulsion polymerization, respectively. The aqueous polymer (W-AM/AMPS) and the inverse emulsion polymer (E-AM/AMPS) were characterized by Fourier transform infrared (FTIR) spectroscopy, nuclear magnetic resonance (1H NMR), transmission electron microscopy (TEM), scanning electron microscopy (SEM), and particle size analysis. The rheological properties, filtration properties, and sodium ion (Na+) and calcium ion (Ca2+) resistance were investigated. The results showed that E-AM/AMPS not only had a dissolution speed 4 times faster than that of W-AM/AMPS but also had superior shear-thinning performance both before and after aging. The filtration property of the bentonite system containing 2 wt % E-AM/AMPS was also better than that of the bentonite system containing 2 wt % W-AM/AMPS. In addition, E-AM/AMPS also exhibited extremely high tolerance for Na+ and Ca2+. The huge difference between rheological and filtration properties of E-AM/AMPS and W-AM/AMPS in drilling fluid can be attributed to the differences in the polymer microstructure caused by the two polymerization methods. Both FTIR and 1H NMR results showed that more hydrogen bonds were formed between E-AM/AMPS molecular groups and molecular chains, which led to a cross-linked network structure of E-AM/AMPS which was observed by TEM. It was this cross-linked network structure that made E-AM/AMPS have a high viscosity and allowed it to be better adsorbed on bentonite particles, thus exhibiting excellent rheological and filtration behavior. In addition, E-AM/AMPS powder had a high specific surface area so that it can be dissolved in water faster, greatly reducing the time and difficulty of configuring drilling fluid.
10.1021/acsomega.0c00665
pubmed_227_7986
Neuronal PAS domain protein 2 (NPAS2) is a circadian rhythm-associated transcription factor with two heme-binding sites on two PAS domains. In the present study, we compared the optical absorption spectra, resonance Raman spectra, heme-binding kinetics and DNA-binding characteristics of the isolated fragment containing the N-terminal basic helix-loop-helix (bHLH) of the first PAS (PAS-A) domain of NPAS2 with those of the PAS-A domain alone. We found that the heme-bound bHLH-PAS-A domain mainly exists as a dimer in solution. The Soret absorption peak of the Fe(III) complex for bHLH-PAS-A (421 nm) was located at a wavelength 9 nm higher than for isolated PAS-A (412 nm). The axial ligand trans to CO in bHLH-PAS-A appears to be His, based on the resonance Raman spectra. In addition, the rate constant for heme association with apo-bHLH-PAS (3.3 x 10(7) mol(-1) x s(-1)) was more than two orders of magnitude higher than for association with apo-PAS-A (< 10(5) mol(-1) x s(-1)). These results suggest that the bHLH domain assists in stable heme binding to NPAS2. Both optical and resonance Raman spectra indicated that the Fe(II)-NO heme complex is five-coordinated. Using the quartz-crystal microbalance method, we found that the bHLH-PAS-A domain binds specifically to the E-box DNA sequence in the presence, but not in the absence, of heme. On the basis of these results, we discuss the mode of heme binding by bHLH-PAS-A and its potential role in regulating DNA binding.
10.1111/j.1742-4658.2006.05259.x
pubmed_245_9411
Rapid progress has been made toward small interfering RNA (siRNA)-based therapy for human disorders, but rationally optimizing siRNAs for high specificity and potent silencing remains a challenge. In this study, we explored the effect of chemical modification at the cleavage site of siRNAs. We found that modifications at positions 9 and 10 markedly reduced the silencing potency of the unmodified strand of siRNAs but were well tolerated by the modified strand. Intriguingly, addition of the 2'-methoxyethyl (MOE) group at the cleavage site improved both the specificity and silencing activity of siRNAs by facilitating the oriented RNA-induced silencing complex (RISC) loading of the modified strand. Furthermore, we combined MOE modifications at positions 9 and 10 of one strand together with 2'-O-methylation (OMe) at position 14 of the other strand and found a synergistic effect that improved the specificity of siRNAs. The surprisingly beneficial effect of the combined modification was validated using siRNA-targeting endogenous gene intercellular adhesion molecule 1 (ICAM1). We found that the combined modifications eliminated its off-target effects. In conclusion, we established effective strategies to optimize siRNAs using site-specific MOE modifications. The findings may allow the creation of superior siRNAs for therapy in terms of activity and specificity.
10.1016/j.omtn.2017.10.003
pubmed_587_11959
Gentris Corporation is engaged in the development and rapid commercialization of innovative proprietary clinical pharmacogenomic products and services. The company provides global pharmaceutical research organizations with turn-key pharmacogenomic solutions to improve the efficiency and predictability of drug development. The ultimate benefit to these organizations is to shorten drug development cycles, improve new drug approval rates and allow marginal drugs to advance towards final approval. In the near future, the company will develop specialized, high quality, reliable diagnostic products, which will provide physicians and their patients with access to pharmacogenomic testing, as personalized medicine becomes the new standard of medical practice.
10.1517/14622416.3.1.148
pubmed_834_14834
Metabolism of contraceptive compounds may be influenced by various drugs. Of clinical importance is induction by barbiturates, by diphenylhydantoin, and especially by rifampicin, of enzymes that are responsible for degradation of estrogens. The major target is the hepatic microsomal estrogen-2-hydroxylase (cytochrome P450 3A4). Another type of interaction of drugs with disposition and effectiveness of estrogens is impairment of their enterohepatic circulation. This may be due to absorption of biliary estrogen conjugates (e.g., by cholestyramine) or to insufficient cleavage of the conjugate by intestinal bacteria, the latter being observed after administration of antibiotics (e.g., ampicillin, neomycin).
10.1289/ehp.94102s935
pubmed_613_11633
A new approach for target quantitative analysis for comprehensive two-dimensional gas chromatography (GC × GC), interval Multi-way Partial Least Square (iNPLS) is presented and evaluated in this paper. In iNPLS, the two-dimensional chromatogram is split in small sections; each of these pieces is treated as an independent new chromatogram. Separated conventional NPLS calibration models for the concentration of the target analyte are built for each of the pieces of the whole chromatogram, and the best model is selected for quantitative analysis. An algorithm for iNPLS running on MatLab platform was written, preliminarily evaluated with using solutions of model compounds with different chemical properties and subsequently applied to quantify some allergens in perfume samples. The results were found to be adequate, and good precision and accuracy was obtained even for poorly resolved peaks.
10.1016/j.talanta.2010.08.015
pubmed_704_15129
Effects-directed analysis (EDA) is used to identify the principal toxic components within a complex mixture using iterative steps of chemical fractionation guided by bioassay results. Bioassay selection can be limited in EDA because of the volume requirements for many standardized test methods, and therefore, a reduced-volume acute toxicity test that also provides whole-organism responses is beneficial. To address this need, a static, 7-d, water-only, reduced-volume method (50 mL, 10 organisms) was developed for Hyalella azteca that substantially decreases the volume requirements of standard-volume acute test exposures (200-500 mL of test solution, 15-20 organisms) while maintaining water quality and meeting control survival criteria. Standard- and reduced-volume methods were compared by conducting concurrent toxicity tests with 2 inorganic toxicants (KCl and CdCl2 ) and 2 organic mixtures of naphthenic acid fraction components (NAFCs) to evaluate test performance. There was no difference between methods when comparing the median lethal concentrations (LC50s) for KCl and both NAFC mixtures (p > 0.05). The LC50s for CdCl2 were statistically different (p = 0.0002); however, this was not considered biologically meaningful because the difference between LC50s was <2-fold. In conclusion, the reduced-volume H. azteca test method generated results comparable to standard-volume test methods and is suitable for use in situations where limited testing material is available, such as when conducting EDA. Environ Toxicol Chem 2020;39:2221-2227. © Her Majesty the Queen in Right of Canada 2020. Reproduced with the permission of the Minister of Environment and Climate Change Canada.
10.1002/etc.4840
pubmed_177_25579
OBJECTIVE To conduct a prospective randomised study comparing the safety, effectiveness and treatment outcomes in patients undergoing bipolar transurethral resection of the prostate (bTURP) and photoselective vaporisation of the prostate (PVP) under sedoanalgesia, as sedoanalgesia is a safe and effective technique suitable for minimally invasive endourological procedures and although studies have confirmed that both TURP and PVP are feasible under sedoanalgesia there are none comparing the two. PATIENTS AND METHODS Between November 2014 and April 2016, all patients satisfying the eligibility criteria underwent either bTURP or PVP under sedoanalgesia after randomisation. The groups were compared for functional outcomes, visual analogue scale (VAS) pain scores (range 0-10), perioperative variables and complications, with a follow-up of 3 months. RESULTS In all, 42 and 36 patients underwent bTURP and PVP under sedoanalgesia, respectively. The mean VAS pain score was <2 at any time during the procedure, with no conversions to general anaesthesia. PVP patients had a shorter operating time [mean (SD) 55.64 (12.8) vs 61.79 (14.2) min, P = 0.035], shorter duration of hospitalisation [mean (SD) 14.58 (2.81) vs 19.21 (2.82) h, P < 0.001] and a higher dysuria rate when compared to bTURP patients. However, the catheterisation time was similar and both intraoperative and postoperative complications were minimal and comparable. Improvements in the International Prostate Symptom Score, quality of life, prostate volume, maximum urinary flow rate and post-void residual urine volume at 3 months were similar in both groups. None of our patients required re-admission or re-operation. CONCLUSION Both PVP and bTURP can be carried out safely under sedoanalgesia with excellent treatment outcomes.
10.1016/j.aju.2017.06.004
pubmed_930_2762
A total of 70 patients with malignant lymphomas refractory to one or more chemotherapeutic regimens were treated with iv amsacrines (m-AMSA and m-AMSA lactate). Of 58 evaluable patients, 12 had Hodgkin's disease and 46 had non-Hodgkin's lymphoma. Twenty-nine of the evaluable patients received m-AMSA and 29 received m-AMSA lactate. The amsacrines were recycled every 3 weeks. The doses of m-AMSA were 90-120, 70, and 25-30 mg/m2/day for 3 days, respectively. All patients treated with m-AMSA lactate received a single dose of 225 mg/m2. In Hodgkin's disease, the response rate was 58.3% (one complete response among 12 patients), and in non-Hodgkin's lymphoma, the response rate was 30.4% (six complete responses among 46 patients). The median duration of response was 3 and 5 months, respectively. The response rate was unfavorably affected by the presence of extra-nodal disease and a Karnofsky performance status less than 80. There was no important difference in the incidence and duration of response between m-AMSA and m-AMSA lactate. After vomiting, myelosuppression was the most frequent observed toxic effect. One patient showed an unexpected fatal bone marrow aplasia following the first course of 90 mg/m2. This study indicates that m-AMSA and m-AMSA lactate are active and moderately toxic in previously treated malignant lymphomas. Thus, amsacrines could be effectively incorporated into salvage polydrug regimens.
pubmed_930_2762
pubmed_182_15039
The article describes the results of a retrospective analysis of medical records of 395 patients with a clinical diagnosis of leptospirosis treated at the Lviv Oblast Infectious Disease Clinical Hospital (Ukraine) between 2002 and 2016. The main risk factors for leptospirosis were contact with rodents or their excrements (26.84%) and bathing in ponds, small lakes, and reservoirs (10.63%). Among 276 patients in whom the anti-leptospira antibodies were detected by the microscopic agglutination test (MAT), the most common serotypes were Leptospira icterohaemorrhagiae (33.33%) and Leptospira grippotyphosa (25.0%). The mortality rate was significantly higher in patients where leptospirosis diagnosis was established based on clinical symptoms without confirmation by MAT (15.13% vs. 5.43%, p < 0.01).
10.1089/vbz.2018.2375
pubmed_904_3917
The ATP-binding cassette (ABC) transporter MsbA is an ATP-driven lipid-A flippase. It belongs to the ABC protein superfamily whose members are characterized by conserved motifs in their nucleotide binding domains (NBDs), which are responsible for ATP hydrolysis. Recently, it was found that MsbA could catalyze a reverse adenylate kinase (rAK)-like reaction in addition to ATP hydrolysis. Both reactions are connected and mediated by the same conserved NBD domains. Here, the structural foundations underlying the nucleotide binding to MsbA were therefore explored using a concerted approach based on conventional- and DNP-enhanced solid-state NMR, pulsed-EPR, and MD simulations. MsbA reconstituted into lipid bilayers was trapped in various catalytic states corresponding to intermediates of the coupled ATPase-rAK mechanism. The analysis of nucleotide-binding dependent chemical shift changes, and the detection of through-space contacts between bound nucleotides and MsbA within these states provides evidence for an additional nucleotide-binding site in close proximity to the Q-loop and the His-Switch. By replacing Mg2+ with Mn2+ and employing pulsed EPR spectroscopy, evidence is provided that this newly found nucleotide binding site does not interfere with the coordination of the required metal ion. Molecular dynamic (MD) simulations of nucleotide and metal binding required for the coupled ATPase-rAK mechanism have been used to corroborate these experimental findings and provide additional insight into nucleotide location, orientation, and possible binding modes.
10.1021/jacs.8b06739
pubmed_656_14522
BACKGROUND Early adulthood is a period of rapid personal development when individuals experience major life transitions (e.g. leaving the parental home, leaving education, beginning employment, cohabitation and parenthood). Changes in social and physical environments associated with these transitions may influence development of health-related behaviours. Consumption of fast food is one behaviour associated with poor diet and long-term health outcomes. In this study we assess how frequency of fast food consumption changes across early adulthood, and how major life transitions are associated with changes in fast food intake. METHODS Data were collected across four waves of the Project EAT study, from mean age 14.9 (SD = 1.6) to mean age 31.1 (SD = 1.6) years. Participants reporting data at two or more waves were included (n = 2902). Participants reported past week frequency of eating food from a fast food restaurant and responded to questions on living arrangements, education and employment participation, and having children. To assess changes in fast food we developed a latent growth model incorporating an underlying trajectory of fast food intake, five life transitions, and time-invariant covariates. RESULTS Mean fast food intake followed an underlying quadratic trajectory, increasing through adolescence to a maximum of 1.88 (SE 0.94) times/week and then decreasing again through early adulthood to 0.76 (SE 2.06) times/week at wave 4. Beginning full-time employment and becoming a parent both contributed to increases in fast food intake, each resulting in an average increase in weekly fast food intake of 0.16 (p < 0.01) times/week. Analysis of changes between pairs of waves revealed stronger associations for these two transitions between waves 1-2 (mean age 14.9-19.4 years) than seen in later waves. Leaving the parental home and beginning cohabitation were associated with decreases in fast food intake of - 0.17 (p = 0.004) and - 0.16 (p = 0.007) times/week respectively, while leaving full-time education was not associated with any change. CONCLUSIONS The transitions of beginning full-time employment and becoming a parent were associated with increases in fast food intake. Public health policy or interventions designed to reduce fast food intake in young adults may benefit from particular focus on populations experiencing these transitions, to ameliorate their impact.
10.1186/s12966-020-01024-4
pubmed_95_20447
High radioactivity in liver and kidney after administration of 99mTc-labeled antibodies is a major detriment to the use of radiolabeled antibodies for diagnosis and therapy. In the present study, the uptake mechanism of radioactivity by liver and kidney involving 99mTc moiety was investigated. The data of in vitro and in vivo thiol transchelation studies, biodistribution alteration of 99mTc-MAb after specific modulation of endogenous thiol containing compounds, and the finding of 99mTc-labeled cysteine and GSH in bile, urine and kidney after administration of 99mTc-MAb demonstrated that transchelation by thiols (cysteine and GSH) played an important role in the localization of radiotracer from 99mTc MAb in normal tissues such as liver and kidney.
pubmed_95_20447
pubmed_429_5594
The author evaluated the precipitating antibrain antibodies by the Hoigne' method in the blood serum of 292 patients and in the CSF of 194 patients with acute brain traumas. Accordingly 52 and 21 patients were studied in the remote period. Antibodies were revealed more frequently and for a longer period of time following severe damages and less frequently in mild forms. They could also be revealed in patients with residual symptoms of brain trauma. Antibodies were revealed in the CSF earlier, more frequently and for a longer period of time than in the blood sera. These data speak in favour of a probable local formation of antibrain antibodies.
pubmed_429_5594
pubmed_1093_11757
In the first decade of the 21st century, we have seen the completion of the human genome project and marked progress in the human microbiome project. The vast amount of data generated from these efforts combined with advances in molecular and biomedical technologies have led to the development of a multitude of assays and technologies that may be useful in the diagnosis and management of infectious diseases. Here, we identify several new assays and technologies that have recently come into clinical use or have potential for clinical use in the near future. The scope of this review is broad and includes topics such as the serum marker procalcitonin, gene expression profiling, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), and nucleic acid aptamers. Principles that underlie each assay or technology, their clinical applications, and potential strengths and limitations are addressed.
10.1093/cid/cis1014
pubmed_377_19525
MicroRNA (miRNA), evolutionarily conserved, endogenous, small, noncoding RNA molecule of about 22 nucleotides in length, have been recently attributed a crucial role in numerous physiological and pathological processes including the regulation of cellular development, differentiation, proliferation, apoptosis and oncogenesis. Myelodysplastic syndrome (MDS) is a heterogeneous group of clonal hematologic disorders characterized clinically and morphologically by ineffective hematopoiesis and increased risk of leukaemic transformation. The role of miRNA abnormal expression in pathogenesis and prognosis of MDS is reviewed in this article, including miRNA related with pathogenesis, miRNA related with prognosis of MDS and so on.
pubmed_377_19525
pubmed_283_1341
OBJECTIVE LIPA gene mutations result in deficiency of lysosomal acid lipase and present phenotypically as Wolman disease or cholesteryl ester storage disease (CESD) depending on the level of deficiency. Patients with CESD may often be misdiagnosed because symptoms may be nonspecific. Symptoms may present in infancy if there is complete loss of lysosomal acid lipase or in early childhood or adulthood when there is partial loss. The purpose of the present study is to review the literature for pediatric cases of CESD to better understand the phenotype of CESD. METHODS A PubMed search of all English-language publications from 1966 through June 2012 for pediatric CESD case reports using the following key words CESD, fatty liver, and NAFLD was performed. All of the cases were reviewed and information regarding age, sex, presenting symptoms, and pertinent laboratory tests were recorded. RESULTS Seventy-one cases were culled from 39 published case reports. Nearly two-thirds of these patients presented with their first symptoms when they were younger than 5 years. Hepatomegaly and splenomegaly were common features. Serum transaminases and lipids were often elevated. Gastrointestinal symptoms were noted in approximately one-third of cases. Two-thirds of patients had liver fibrosis. CONCLUSIONS CESD has an estimated incidence as high as 1 in 40,000, which means that it is presently underdiagnosed. Education about common symptoms of CESD as well as a higher level of suspicion for screening for CESD will lead to earlier diagnosis. New treatments for CESD including possible enzyme replacement therapy make early diagnosis especially important.
10.1097/MPG.0b013e31828b36ac
pubmed_987_11923
INTRODUCTION The treatment of Lumbar Disc Herniation (LDH) in elite athletes is a debated topic that lacks consensus in the literature due to varying outcome reporting methods. The objective of this study was to quantify the overall performance of a sample of professional athletes before and after receiving a lumbar discectomy or microdiscectomy in a cohort of players in the National Football League (NFL), National Basketball Association (NBA), National Hockey League (NHL) and Major League Baseball (MLB). METHODS The authors identified publicly accessible data from a cohort of different types of professional players who received either a lumbar discectomy or a microdiscectomy. These records were identified through newspaper archives, injury reports, player profiles and press releases between 1993 through 2015. Fantasy and Wins Above Replacement (WAR) scores were calculated for each player. RESULTS A total of 38 professional players met study inclusion criteria. NFL players had the lowest return-to-play (RTP) at nine of 14 (64%). The RTP for NBA, NHL and MLB players were comparable with 6/7 (86%) vs 8/9 (89%) vs 7/8 (88%). NFL players had the lowest average career length after surgery at 34.8 months, while NBA players had the longest average career length at 48 months. MLB players on average required the longest time to return to presurgical level of performance (24 months) and required the longest average recovery time at 12 months. CONCLUSIONS Based on these results, the average performance of most elite athletes are likely to decrease after undergoing a lumbar discectomy. Although it appears that performance peaks in the initial years after the operation for some players, there was an overall long-term decline in this sample of elite athletes. Study limitations included small sample size, lack of controlling for possible confounding variables (e.g., age, etc.) and use of variable reporting sources. Additional studies with larger sample sizes and age-matched controls are needed to examine the effects of lumbar discectomy more comprehensively in elite athletes.
10.51894/001c.30766
pubmed_409_9214
Biological monitoring of workers exposed to toxic substances has been used for many years for a variety of differing purposes. This has caused some confusion amongst the professions concerned as to its proper use in any defined circumstances. This paper attempts to clarify the position, particularly as regards the role of biological monitoring in occupational hygiene practice.
10.1093/annhyg/34.3.315
pubmed_363_23896
A previously published liquid chromatographic method for determining residues of nine quinolones in chicken, porcine, bovine and ovine muscle was adapted and applied to fish tissue for simultaneous determination of three quinolones (flumequine, oxolinic acid and sarafloxacin). The analytes were extracted from homogenised muscle using an acetonitrile basic solution. After centrifugation, partial evaporation and cleaning with hexane, direct injection was possible. Separation was achieved on PLRP-S column and detection was performed with a programmable fluorescence detector. Chromatographic conditions were optimised to be compatible with the determination of the three quinolones in a single run. The linearity, recovery, accuracy and precision of the method were evaluated from fortified tissue samples at concentration levels ranging from 15 to 120 microg kg(-1) for sarafloxacin and 75 to 600 microg kg(-1) for oxolinic acid and flumequine according to the EU maximum residue limit of each quinolone. The limits of detection were estimated to be 2, 5 and 7 microg kg(-1), respectively, for sarafloxacin, oxolinic acid and flumequine. The limits of quantification were validated at 15 microg kg(-1) for sarafloxacin and 75 microg kg(-1) for oxolinic acid and flumequine. Mean extraction recoveries of quinolones in fish ranged from 56.9 to 71.0%. This simple and rapid method is suitable for residue control.
10.1016/s1570-0232(02)00641-4
pubmed_678_6493
In this study, we investigated the potential of a dual-targeted pH-sensitive doxorubicin prodrug-microbubble complex (DPMC) in ultrasound (US)-assisted antitumor therapy. The doxorubicin prodrug (DP) consists of a succinylated-heparin carrier conjugated with doxorubicin (DOX) via hydrazone linkage and decorated with dual targeting ligands, folate and cRGD peptide. Combination of microbubble (MB) and DP, generated via avidin-biotin binding, promoted intracellular accumulation and improved therapeutic efficiency assisted by US cavitation and sonoporation. Aggregates of prepared DP were observed with an inhomogeneous size distribution (average diameters: 149.6±29.8 nm and 1036.2±38.8 nm, PDI: 1.0) while DPMC exhibited a uniform distribution (average diameter: 5.804±2.1 μm), facilitating its usage for drug delivery. Notably, upon US exposure, DPMC was disrupted and aggregated DP dispersed into homogeneous small-sized nanoparticles (average diameter: 128.6±42.3 nm, PDI: 0.21). DPMC could target to angiogenic endothelial cells in tumor region via αvβ3-mediated recognition and subsequently facilitate its specific binding to tumor cells mediated via recognition of folate receptor (FR) after US exposure. In vitro experiments showed higher tumor specificity and killing ability of DPMC with US than free DOX and DP for breast cancer MCF-7 cells. Furthermore, significant accumulation and specificity for tumor tissues of DPMC with US were detected using in vivo fluorescence and ultrasound molecular imaging, indicating its potential to integrate tumor imaging and therapy. In particular, through inducing apoptosis, inhibiting cell proliferation and antagonizing angiogenesis, DPMC with US produced higher tumor inhibition rates than DOX or DPMC without US in MCF-7 xenograft tumor-bearing mice while inducing no obvious body weight loss. Our strategy provides an effective platform for the delivery of large-sized or aggregated particles to tumor sites, thereby extending their therapeutic applications in vivo.
10.7150/thno.16677
pubmed_171_21648
OBJECTIVE Globally in 2000, 1.2 million deaths resulted from road traffic injury (RTI) and about 10 times this number were injured. Because of the size of the problem, its expected growth and its preventability, World Health Day 2004 (April 7) was devoted to RTI. This review highlights attention to RTI by the ANZJPH and investigates relevance to the developing world, where 90% of all RTI deaths now occur. METHOD All articles published by the ANZJPH over the five-year period 1999-2004, which met the World Health Organization definition of RTI, were reviewed. RESULTS The eight studies selected and reviewed focused particularly on young drivers, alcohol use and Indigenous Australians, using a range of research and evaluation methods. Risk factors identified including widespread risky driving behaviour by young males and alcohol involvement. Intervention successes included legislative change regarding utility passengers, current vehicle inspection certificate and effects associated with the lead-up to New Zealand's 1992 Transport Act. CONCLUSIONS The dramatic and continued reduction in Australia's road toll following peak rates in the 1960s has relied on scientific research, such as that reviewed here, for its effective evidence base. This review indicates that RTI is established on the public health agenda in Australia--a key aim of WHO's five-year strategy, for emulation by developing regions and nations. IMPLICATIONS High-income countries such as Australia and New Zealand have the knowledge, expertise and also the responsibility to assist regional low- and middle-income countries to counter the growing scourge of RTI that accompanies rapid motorisation.
10.1111/j.1467-842x.2004.tb00921.x
pubmed_677_4877
Taxol (paclitaxel) is known to inhibit cell growth and trigger significant apoptosis in various cancer cells. Although taxol induces apoptosis of cancer cells, its exact mechanism of action is not yet known. In this study we investigated death receptors, FAS-associated death domain protein (FADD), the activation of caspases-10 and -8 as well as the downstream caspases, and reactive oxygen species (ROS) in taxol-induced apoptosis in the CCRF-HSB-2 human lymphoblastic leukemia cell line. Pretreating the cells with neutralizing antibodies to Fas, tumor necrosis factor (TNF)-alpha receptor 1, or TNF-related apoptosis-inducing ligand receptors (DR4 and DR5) did not affect taxol-induced apoptosis, but transfection of the cells with a dominant negative FADD plasmid resulted in inhibition of taxol-induced apoptosis, revealing that taxol induces apoptosis independently of these death receptors but dependently on FADD. Furthermore, the drug induced activation of caspases-10, -8, -6, and -3, cleaved Bcl-2, Bid, poly(ADP-ribose) polymerase, and lamin B, and down-regulated cellular levels of FLICE-like inhibitory protein (FLIP) and X-chromosome-linked inhibitor of apoptosis protein (XIAP). However, despite the release of cytochrome c from the mitochondria in taxol-treated cells, caspase-9 was not activated. Inhibitors of caspases-8, -6, or -3 partially inhibited taxol-induced apoptosis, whereas the caspase-10 inhibitor totally abrogated this process. Taxol-induced apoptosis was also associated with decreased mitochondrial membrane potential (Deltapsim) and a significant increase in ROS generation. However, increased ROS production was not directly involved in taxol-triggered apoptosis. Therefore, these results demonstrate for the first time that taxol induces FADD-dependent apoptosis primarily through activation of caspase-10 but independently of death receptors.
10.1074/jbc.M406543200
pubmed_52_1376
We used cDNA array to compare the relative transcript levels of 96 cell cycle-related genes in mouse primordial germ cells (PGCs), embryonic germ (EG) cells and embryonic stem (ES) cells. Among 38 genes of the G1 phase analysed, Ccnd3 (CyclinD3), Cdkn1c (p57(kip2)), Rb1, and Tceb1l (Skip1-like) were expressed at significantly higher levels in PGCs than in EG and ES cells; Ccnd1 (CyclinD1) was more abundant in EG cells than in PGCs. Except for higher mRNA levels of Ccng (CyclinG1) in EG and ES cells in comparison to PGCs, no difference among 20 genes of the S and 12 genes of G2/M phases was found. Less than half of the 26 genes regarded as DNA damage checkpoint/Trp53/Atm pathway genes showed significant transcript levels in all three cell populations. Among these, the transcript levels of Ube1x and Atm were significantly higher in PGCs than in EG and ES cells while that of Ube3a was higher in these latter. In addition, relatively high mRNA levels of Timp3 characterizes EG cells while transcripts of this gene were very low in PGCs and barely detectable in ES cells. With the exception of Tceb1l, differential transcript levels found in the cDNA array assay were confirmed by real time RT-PCR. Using this method, we also analysed the transcripts of two genes not present in the cDNA array: c-myc, known to be critical for the control of cell cycle in many cell types, and Eras, specifically expressed in ES cells and involved in the control of ES cell proliferation and their tumorigenic properties. While c-myc transcripts were present at similar levels in all three cell types examined, Eras was expressed at high levels in ES cells (10-fold) and even more so in EG cells (almost 40-fold) in comparison to PGCs. Taken together, these results indicate that despite similarities between PGCs and ES or EG cells, their cell cycles are differently regulated. In particular, it appears that PGCs, like most mitotic cells, possess a more regulatable control of G1 phase than EG and ES cells. Moreover, our data provide useful clues for further studies aimed at identifying cell cycle genes critical for PGC growth and their transformation in tumorigenic cells.
10.1016/j.modgep.2007.02.002
pubmed_1124_6436
Several models of the development of infant visual attention have used information about neural development. Most of these models have been based on nonhuman animal studies and have relied on indirect measures of neural development in human infants. This article discusses methods for studying a "neurodevelopmental" model of infant visual attention using indirect and direct measures of cortical activity. We concentrate on the effect of attention on eye movement control and show how animal-based models, indirect measurement in human infants, and direct measurement of brain activity inform this model.
10.1002/dev.10029
pubmed_328_23380
BACKGROUND Moderate to deep sedation is required for an auditory brainstem response test when high-intensity stimulation is used. Chloral hydrate is the most commonly used sedative, whereas intranasal dexmedetomidine is increasingly used in pediatric non-painful procedural sedations. OBJECTIVE The aim of this study was to compare the sedation success rate after oral chloral hydrate at 50 mg kg-1 and intranasal dexmedetomidine at 3 μg kg-1 plus buccal midazolam at 0.1 mg kg-1 for an auditory brainstem response test. METHODS Children who required an auditory brainstem response test were recruited and randomly assigned to receive oral chloral hydrate at 50 mg kg-1 and intranasal placebo, or intranasal dexmedetomidine at 3 μg kg-1 with buccal midazolam 0.1 mg kg-1 . The primary outcome was the rate of successful sedation for auditory brainstem response tests. RESULTS Fifty-seven out of 82 (69.5%) were successfully sedated after chloral hydrate, while 70 out of 78 (89.7%) children were successfully sedated with dexmedetomidine plus midazolam combination, with the odd ratio (95% CI) for successful sedation between dexmedetomidine plus midazolam combination and chloral hydrate estimated to be 3.84 (1.61-9.16), P = 0.002. Dexmedetomidine plus midazolam was associated with quicker onset with median onset time 15 (IQR 11.0-19.8) for dexmedetomidine plus midazolam and 20 (IQR 15.0-27.0) for chloral hydrate respectively, with difference between median (95% CI) of 5 [3-8], P < 0.0001). The behavior observed during drug administration of intranasal dexmedetomidine and buccal midazolam was better that of the children who had oral chloral hydrate. No children required oxygen therapy or medical intervention for hemodynamic disturbances in this study and the incidence of hypotension and bradycardia was similar. CONCLUSION Intranasal dexmedetomidine plus buccal midazolam was associated with higher sedation success with deeper level of sedation, with similar discharge time and adverse event rate when compared to chloral hydrate.
10.1111/pan.13498
pubmed_1094_14499
INTRODUCTION Diagnosis of Tuberculosis (TB) in children is difficult because the clinical presentation is not specific, the chest X-ray interpretation has low accuracy and sputum sample is difficult to obtain. Antigen detection test such as rapid urine LAM is a non-invasive alternative for diagnosing TB . Lipoarabinomannan (LAM) is the main component of M.tuberculosis cell wall. AIM To determine the diagnostic value of urinary LAM antigen for diagnosis of childhood TB. MATERIALS AND METHODS In the present cross-sectional study, subjects were included using consecutive sampling method. All the children aged 0-14 years Suspected of pulmonary or extra pulmonary TB suffering from cough more than two weeks, fever without clear aetiology, loss of body weight or poor weight gain, fatigue, malaise, chronic lymph node enlargement, spine angulation, joint swelling and had history of contact with positive sputum smear adult TB patient were enrolled in the study. Pulmonary and extra pulmonary diagnosis was based on clinical presentation, Tuberculin Skin Test (TST), chest X-ray, Acid Fast Bacillus (AFB) staining and or sputum culture. Urinary LAM level was measured by using Enzyme-Linked Immunosorbent Assay (ELISA). Cut off value and Area Under the Curve (AUC) were determined using ROC statistical analysis (SPSS 21.0). Sensitivity and specificity was measured from 2x2 cross table. RESULTS Out of 61 subjects suspected as TB, 49 (80.3%) were eventually diagnosed with TB. Of those diagnosed with TB, 21 (42.9%) were microbiologically confirmed cases either by sputum microscopy (34.7%) or culture (8.2%), whereas 28 subjects were unconfirmed cases (57.1%). The urinary LAM level was higher in subjects with TB (1.80+1.02) mg/l compared to non-TB group (0.46+0.3) mg/l; p<0.001(independent t-test). Urine LAM had 83% sensitivity and 85% specificity with cut off value 0.98 mg/l using microbiological and clinical confirmation as standard reference and 33% sensitivity and 60% specificity with cut off value 1.69 mg/l using microbiological confirmation only. CONCLUSION Urinary LAM has good diagnostic value for childhood TB diagnosis.
10.7860/JCDR/2017/20909.9542
pubmed_235_3640
We used density functional theory calculations to investigate the physical origin of the mechanochemical response of material interfaces. Our results show that the mechanochemical response can be decomposed into the contribution from the interface itself (deformation of interfacial bonds) and a contribution from the underlying solid. The relative contributions depend on the stiffness of these regions and the contact geometry, which affects the stress distribution within the bulk region. We demonstrate that, contrary to what is commonly assumed, the contribution to the activation volume from the elastic deformation of the surrounding bulk is significant and, in some case, may be dominant. We also show that the activation volume and the mechanochemical response of interfaces should be finite due to the effects on the stiffness and stress distribution within the near-surface bulk region. Our results indicate that the large range of activation volumes measured in the previous experiments even for the same material system might originate from the different degrees of contributions probed from the bulk vs interface.
10.1103/PhysRevLett.126.076001
pubmed_135_16837
Beneficial associations with bacteria are widespread across animals, spanning a range of symbiont localizations, transmission routes, and functions. While some of these associations have evolved into obligate relationships with permanent symbiont localization within the host, the majority require colonization of every host generation from the environment or via maternal provisions. Across the broad diversity of host species and tissue types that beneficial bacteria can colonize, there are some highly specialized strategies for establishment yet also some common patterns in the molecular basis of colonization. This review focuses on the mechanisms underlying the early stage of beneficial bacterium-invertebrate associations, from initial contact to the establishment of the symbionts in a specific location of the host's body. We first reflect on general selective pressures that can drive the transition from a free-living to a host-associated lifestyle in bacteria. We then cover bacterial molecular factors for colonization in symbioses from both model and nonmodel invertebrate systems where these have been studied, including terrestrial and aquatic host taxa. Finally, we discuss how interactions between multiple colonizing bacteria and priority effects can influence colonization. Taking the bacterial perspective, we emphasize the importance of developing new experimentally tractable systems to derive general insights into the ecological factors and molecular adaptations underlying the origin and establishment of beneficial symbioses in animals.
10.1128/mmbr.00126-21
pubmed_999_1502
OBJECTIVE This randomized clinical trial aimed to compare the short-term postsurgical symptoms after insertion of one or two implants for retention of a mandibular overdenture. This study investigated whether the less invasive single-implant approach results in lower postoperative symptoms compared to the conventional two-implant overdenture. MATERIALS AND METHODS Patients received new complete dentures and were randomly assigned to groups receiving one or two single-stage, early-loaded hydrophilic implants, inserted in the midline (n = 23), or the lateral incisor-canine area bilaterally (n = 24). Patient-reported postoperative symptoms were measured in a 0-100 visual analogue scale concerning pain in the surgical area, pain when chewing, bleeding, swelling, and unpleasantness. Data collection occurred 24 h and 7 and 21 days after surgery. Demographic and clinical features (smoking habit, classification of the residual ridges, and mucosal width and thickness at the implant sites), osteotomy for alveolar bone reduction, and surgery time were tested as predictors of symptom levels. RESULTS Overall reported symptoms were mild and self-limited, with high rates of complete remission after the early loading period of 3 weeks. Progressive improvement of symptoms occurred from the 24-h to the 7-day and 21-day follow-ups (p < 0.001), similarly in both groups. None of the clinical predictors was significantly associated with the changes in symptoms. CONCLUSIONS Findings suggest that the insertion of one or two implants may result in similar postoperative outcomes. CLINICAL RELEVANCE The severity of short-term postoperative symptoms may not be a critical factor for the decision between overdenture treatment with one or two implants.
10.1186/s40729-021-00321-2
pubmed_148_2019
Forced plantar flexion can result in tibiotalar dislocation, subtalar dislocation and total dislocation of the talus. Forced dorsal flexion can cause fracture of the neck of the talus, with or without subtalar dislocation, or dislocation of the body of the bone. Accurate diagnosis is important and sometimes difficult. Reduction must be prompt. Complications include osteomyelitis, malunion and avascular necrosis of the talar body. The last may be partial and revascularization can occur.
pubmed_148_2019
pubmed_196_4460
BACKGROUND/AIMS Like nucleated cells, erythrocytes (red blood cells, RBCs) are capable of executing programmed cell death pathways. RBCs undergo necroptosis in response to CD59-specific pore-forming toxins (PFTs). The relationship between blood bank storage and RBC necroptosis was explored in this study. METHODS Human RBCs were stored in standard blood bank additive solutions (AS-1, AS-3, or AS-5) for 1 week and hemolysis was evaluated in the context of necroptosis inhibitors and reactive oxygen species (ROS) scavengers. Activation of key factors including RIP1, RIP3, and MLKL was determined using immunoprecipitations and western blot. RBC vesiculation and formation of echinocytes was determined using phase-contrast microscopy. The effect of necroptosis and storage on RBC clearance was determined using a murine transfusion model. RESULTS Necroptosis is associated with increased RBC clearance post-transfusion. Moreover, storage in AS-1, AS-3, or AS-5 sensitizes RBCs for necroptosis. Importantly, storage-sensitized RBCs undergo necroptosis in response to multiple PFTs, regardless of specificity for CD59. Storage-sensitized RBCs undergo necroptosis via NADPH oxidase-generated ROS. RBC storage led to RIP1 phosphorylation and necrosome formation in an NADPH oxidase-dependent manner suggesting the basis for this sensitization. In addition, storage led to increased RBC clearance post-transfusion. Clearance of these RBCs was due to Syk-dependent echinocyte formation. CONCLUSION Storage-induced sensitization to RBC necroptosis and clearance is important as it may be relevant to hemolytic transfusion reactions.
10.33594/000000153
pubmed_335_8982
RG-7916 is a first-in-class drug candidate for the treatment of spinal muscular atrophy (SMA) that functions by modulating pre-mRNA splicing of the SMN2 gene, resulting in a 2.5-fold increase in survival of motor neuron (SMN) protein level, a key protein lacking in SMA patients. RG-7916 is currently in three interventional phase 2 clinical trials for various types of SMA. In this report, we show that SMN-C2 and -C3, close analogs of RG-7916, act as selective RNA-binding ligands that modulate pre-mRNA splicing. Chemical proteomic and genomic techniques reveal that SMN-C2 directly binds to the AGGAAG motif on exon 7 of the SMN2 pre-mRNA, and promotes a conformational change in two to three unpaired nucleotides at the junction of intron 6 and exon 7 in both in vitro and in-cell models. This change creates a new functional binding surface that increases binding of the splicing modulators, far upstream element binding protein 1 (FUBP1) and its homolog, KH-type splicing regulatory protein (KHSRP), to the SMN-C2/C3-SMN2 pre-mRNA complex and enhances SMN2 splicing. These findings underscore the potential of small-molecule drugs to selectively bind RNA and modulate pre-mRNA splicing as an approach to the treatment of human disease.
10.1073/pnas.1800260115
pubmed_926_21910
This review includes works published in the general scientific literature during 2016 on the production of bioenergy and biofuel from waste residues generated during bioethanol and biodiesel production with a brief overview of current and emerging feedstocks. A section of this review summarizes literature on culturing algae for biofuels including bioreactors and open pond cultivation systems with the utilization of inorganic and organic sources of nutrients. New methods applicable to the mass culture of algae are highlighted. Algal cell harvesting and oil extraction techniques are discussed along with policies and economics.
10.2175/106143017X15023776270511
pubmed_46_8927
Inhibition of nitric oxide synthase by L-arginine analogues is associated with elevation of blood pressure in rats. Deoxycorticosterone acetate (DOCA)-salt hypertensive rats and DOCA-salt-treated spontaneously hypertensive rats (SHR) overexpress the endothelin-1 gene in blood vessels, and this is associated with severe vascular hypertrophy, whereas SHR do not overexpress endothelin-1 and exhibit limited vascular hypertrophy. In this study malignant hypertension was induced in SHR by chronic administration of the L-arginine analogue NG-nitro-L-arginine methyl ester (L-NAME), a potent inhibitor of nitric oxide synthase, to determine whether malignant hypertension would result in endothelin-1 gene overexpression in blood vessels and in greater severity of vascular hypertrophy, as found in malignant DOCA-salt-treated SHR. L-NAME treatment induced malignant hypertension in SHR, with a systolic blood pressure of 246 +/- 2 mm Hg, compared with 211 +/- 2 mm Hg (P < .01) in untreated SHR. Plasma renin activity was very high in L-NAME-treated SHR, and their plasma immunoreactive endothelin concentration was slightly but significantly elevated (P < .01). After 3 weeks of treatment, aortic and to a lesser degree mesenteric artery weights were significantly increased in L-NAME-treated SHR compared with untreated SHR. However, cardiac weight and the media cross-sectional area or media width-to-lumen diameter ratio of small arteries from the coronary, renal, mesenteric, or femoral vasculature were not increased in L-NAME-treated SHR in comparison with untreated SHR. The abundance of endothelin-1 mRNA measured by Northern blot analysis was significantly increased in L-NAME-treated SHR in aorta and with less magnitude in the mesenteric arterial tree. The absence of accentuation of cardiac and small artery hypertrophy in malignant hypertension in L-NAME-treated SHR, despite enhanced expression of the endothelin-1 gene in blood vessels, may suggest a direct or indirect inhibitory effect of L-NAME on cardiovascular growth, probably independent of its effects on nitric oxide synthase, counterbalanced in aorta and large mesenteric arteries by the hypertrophic effect of enhanced vascular endothelin-1 gene expression. These results also suggest a role for blood pressure and potentially for nitric oxide in the regulation of endothelin-1 gene expression in blood vessels.
10.1161/01.hyp.27.1.49
pubmed_72_6477
The visual wulst of the zebra finch comprises at least two retinotopic maps of the contralateral eye. As yet, it is not known how much of the visual field is represented in the wulst neuronal maps, how the organization of the maps is related to the retinal architecture, and how information from the ipsilateral eye is involved in the activation of the wulst. Here, we have used autofluorescent flavoprotein imaging and classical anatomical methods to investigate such characteristics of the most posterior map of the multiple retinotopic representations. We found that the visual wulst can be activated by visual stimuli from a large part of the visual field of the contralateral eye. Horizontally, the visual field representation extended from -5° beyond the beak tip up to +125° laterally. Vertically, a small strip from -10° below to about +25° above the horizon activated the visual wulst. Although retinal ganglion cells had a much higher density around the fovea and along a strip extending from the fovea towards the beak tip, these areas were not overrepresented in the wulst map. The wulst area activated from the foveal region of the ipsilateral eye, overlapped substantially with the middle of the three contralaterally activated regions in the visual wulst, and partially with the other two. Visual wulst activity evoked by stimulation of the frontal visual field was stronger with contralateral than with binocular stimulation. This confirms earlier electrophysiological studies indicating an inhibitory influence of the activation of the ipsilateral eye on wulst activity elicited by stimulating the contralateral eye. The lack of a foveal overrepresentation suggests that identification of objects may not be the primary task of the zebra finch visual wulst. Instead, this brain area may be involved in the processing of visual information necessary for spatial orientation.
10.1371/journal.pone.0124917
pubmed_825_4283
The homeodomain protein alpha 2 and the SRF-like protein Mcm1 are required to establish cell type in the yeast Saccharomyces cerevisiae. Together, these regulatory proteins recognize a specific DNA operator, marking a set of genes for transcriptional repression. In this paper, we show that occupancy of the operator by alpha 2-Mcm1 is not sufficient to bring about repression. Rather, repression is effected only when Ssn6 (a TPR protein) and Tup1 (a beta-transducin repeat protein) are also present in the cell. We show that Ssn6 represses transcription when brought to a promoter by a bacterial DNA-binding domain and that Tup1 is required for this repression. Based on these and other results, we propose that Ssn6-Tup1 is a general repressor of transcription in yeast, recruited to target promoters by a variety of sequence-specific DNA-binding proteins.
10.1016/0092-8674(92)90146-4
pubmed_244_407
Understanding protein-small-molecule interactions is a critical component of rational drug-design. Structure-activity relationship (SAR)-guided medicinal chemistry is informed by the biological outcome, as assessed by biochemical activity or cellular effect, of chemical modifications on small molecules. The effectiveness of SAR is reliant on the sturdiness and durability of assay design and the quality of information garnered from assays. Lack of quality data at this step can lead to obstruction of the drug discovery pipeline with profound implications for the timelines of introducing a drug into the market. Hence, it would not be an overstatement to consider biochemical/biological assays as the backbone of drug-discovery. Enzyme assays can fail for many different reasons, with the enzyme and the substrate being the principal players. Lack of clarity can hamper progress and can lead to mounting costs and potentially losing competitive advantage. Although each assay is unique and requires a specific approach to troubleshoot the problem at hand, there are general guidelines that can be followed to maximize the chances of success. This review is a step-by-step attempt at reintroducing fundamental biochemical concepts within the context of an enzyme assay, delineating probable causes for failure and potential approaches to get an assay back up and running.
10.1002/med.21670
pubmed_632_4135
Stem cells possess unique properties, such as the ability to self-renew and the potential to differentiate into an organism's various cell types. These make them highly valuable in regenerative medicine and tissue engineering. Their properties are precisely regulated in vivo through complex mechanisms that include multiple cues arising from the cell interaction with the surrounding extracellular matrix, neighboring cells, and soluble factors. Although much research effort has focused on developing systems and materials that mimic this complex microenvironment, the controlled regulation of differentiation and maintenance of stemness in vitro remains elusive. In this work, we demonstrate, for the first time, that the nanofibrous bacterial cellulose (BC) membrane derived from Komagataeibacter xylinus can inhibit the differentiation of mouse embryonic stem cells (mESC) under long-term conditions (17 days), improving their mouse embryonic fibroblast (MEF)-free cultivation in comparison to the MEF-supported conventional culture. The maintained cells' pluripotency was confirmed by the mESCs' ability to differentiate into the three germ layers (endo-, meso-, and ectoderm) after having been cultured on the BC membrane for 6 days. In addition, the culturing of mESCs on flexible, free-standing BC membranes enables the quick and facile manipulation and transfer of stem cells between culture dishes, both of which significantly facilitate the use of stem cells in routine culture and various applications. To investigate the influence of the structural and topographical properties of the cellulose on stem cell differentiation, we used the cellulose membranes differing in membrane thickness, porosity, and surface roughness. This work identifies bacterial cellulose as a novel convenient and flexible membrane material enabling long-term maintenance of mESCs' stemness and significantly facilitating the handling and culturing of stem cells.
10.1021/acsami.8b01992
pubmed_520_3038
This was a multicenter clinical trial of rituximab, a chimeric monoclonal IgG antibody directed against CD20, for the treatment of refractory pemphigus vulgaris and pemphigus foliaceus. In total, 20 patients were treated with two doses of rituximab (1000 mg; 2 weeks apart) on days 0 and 14. The primary end point was the proportion of patients who achieved complete or partial remission on day 168 following the first rituximab dose. Of the 20 enrolled patients, 11 (55%) and four (20%) achieved complete and partial remission, respectively; therefore, remission was achieved in a total of 15 patients (75.0% [95% confidence interval, 50.9%-91.3%]). It was demonstrated that the remission rate was greater than the prespecified threshold (5%). In addition, a significant improvement in clinical score (Pemphigus Disease Area Index) and decrease in serum anti-desmoglein antibody level were observed over time. Four serious adverse events (heart failure, pneumonia, radial fracture, and osteonecrosis) were recorded in two patients, of which only pneumonia was considered causally related with rituximab. The level of peripheral blood CD19-positive B lymphocytes was decreased on day 28 after rituximab treatment and remained low throughout the study period until day 168. Our results confirm the efficacy and safety of rituximab therapy for refractory pemphigus in Japanese patients.
10.1111/1346-8138.16597
pubmed_890_14749
BACKGROUND Nance-Horan Syndrome (NHS) (OMIM: 302350) is a rare X-linked developmental disorder characterized by bilateral congenital cataracts, with occasional dental anomalies, characteristic dysmorphic features, brachymetacarpia and mental retardation. Carrier females exhibit similar manifestations that are less severe than in affected males. METHODS Here, we report a four-generation Chinese family with multiple affected individuals presenting Nance-Horan Syndrome. Whole-exome sequencing combined with RT-PCR and Sanger sequencing was used to search for a genetic cause underlying the disease phenotype. RESULTS Whole-exome sequencing identified in all affected individuals of the family a novel donor splicing site mutation (NM_198270: c.1045 + 2T > A) in intron 4 of the gene NHS, which maps to chromosome Xp22.13. The identified mutation results in an RNA processing defect causing a 416-nucleotide addition to exon 4 of the mRNA transcript, likely producing a truncated NHS protein. CONCLUSIONS The donor splicing site mutation NM_198270: c.1045 + 2T > A of the NHS gene is the causative mutation in this Nance-Horan Syndrome family. This research broadens the spectrum of NHS gene mutations, contributing to our understanding of the molecular genetics of NHS.
10.1186/s12881-016-0360-9
pubmed_650_18756
The interaction of vitronectin-thrombin-antithrombin III (VN.TAT) complex with endothelial cells (EC) was investigated. Binding was specific and time- and concentration-dependent. Kinetics revealed an apparent dissociation constant of 16 nM and 1.7 x 10(5) binding sites/endothelial cell. The binding determinant of the ternary complex was located on the VN moiety. Since the association of VN to TAT adds its specific properties to the VN.TAT complex, the involvement of the heparin binding domain and the cell attachment site of VN was investigated. Neither addition of RGD peptide nor blocking of the vitronectin receptor with a monoclonal antibody interfered with VN.TAT binding to EC. Addition of heparin, a VN-derived peptide comprising two heparin binding consensus sequences or a monoclonal antibody directed against the heparin binding domain on VN, completely inhibited VN.TAT binding to EC. These results indicate that the interaction is mediated through the heparin binding domain of VN. Digestion of heparan sulfate proteoglycans resulted in a decrease of VN.TAT binding to EC, indicating the involvement of heparin-like structures on the EC surface. Our findings point to an unrecognized mechanism by which VN may act as scavenger in order to enhance the clearance of end products of the clotting system via binding of the ternary VN.TAT complex to the luminal surface of EC.
pubmed_650_18756
pubmed_524_10451
The announcement of the closure of Philadelphia's Hahnemann University Hospital in June 2019 sent shock waves through the academic community. The closure had a devastating impact on the residents and fellows who trained there, the patients who had long received their care there, and faculty and staff who had provided care there for decades. Since its beginnings, the hospital, established as part of Hahnemann Medical College in 1885, was a major site for medical student education. The authors share the planning before and actions during the crisis that protected the educational experiences of third- and fourth-year medical students at Drexel University College of Medicine assigned to Hahnemann University Hospital. The lessons they learned can be helpful to leadership in academic health systems in the United States facing a diminishing number of clinical training sites for medical and other health professions students, a situation that is likely to worsen as the COVID-19 pandemic continues to weaken the health care ecosystem.
10.1097/ACM.0000000000004062
pubmed_980_557
Soft actuators that undergo programmable shape change in response to a stimulus are enabling components of future soft robots and other soft machines. Strategies to power these actuators often require the incorporation of rigid, electrically conductive materials into the soft actuator, thus limiting the compliance and shape change of the material. In this study, we develop a 4D-printable composite composed of liquid crystal elastomer (LCE) matrix with dispersed droplets of eutectic gallium indium alloy (EGaIn). Using deformable EGaIn droplets in place of rigid conductive fillers preserves the compliance and shape-morphing properties of the LCE. The process enables 4D-printed LCE actuators capable of photothermal and electrothermal actuation. At low liquid metal (LM) concentrations (71 wt %), the composite actuator exhibits a photothermal response upon irradiation of near-IR light. Printed actuators with a twisted nematic configuration are capable of bending angles of 150° at 800 mW cm-2. At higher LM concentrations (88 wt %), the embedded LM droplets can form percolating networks that conduct electricity and enable electrical Joule heating of the LCE. Actuation strain ranging from 5 to 12% is controlled by the amount of electrical power that is delivered to the composite. We also introduce a method for multimaterial printing of monolithic structures where the LM filler loading is spatially varied. These multifunctional materials exhibit innate responsivity where the actuator behaves as an electrical switch and can report one of two states (on/off). These multiresponsive, 4D-printable composites enable multifunctional, mechanically active structures that can be powered with IR light or low DC voltages.
10.1021/acsami.0c19051
pubmed_749_12805
This study aimed at comparing the surveillance program of bovine herpesvirus type 1 (BHV1) as laid down by EU Decision 2004/558/EC and 2007/584/EC ('conventional design') with an alternative design. The alternative design was based on monthly bulk-milk testing, clinical surveillance and a risk-based component that involves testing of animals that are purchased from non-free cattle herds. Scenario-tree analyses were carried out to determine sensitivities of the surveillance system (and its components) and the monthly confidence of freedom on herd-level. Also, the expected costs per surveillance design and components thereof were calculated. Results showed that the conventional (EU) and alternative surveillance designs to obtain a BHV1-free status performed equally well in terms of sensitivity. However, total costs per cattle herd to obtain a free status were highest in the conventional design. In an endemic situation and with a within-herd design prevalence of 10%, the conventional design led to a varying probability of freedom ranging from 99.6% to 100% per month. With the alternative design, in this situation, a constant probability of freedom of >99.9% per month was found. In a disease-free situation, both designs performed equally well (probability of freedom >99.9% per month). The yearly costs per farm for monitoring the disease-free status decreased by approximately 25% in the alternative design. The alternative strategy based on monthly bulk-milk monitoring therefore was deemed most cost-effective. This study showed that the surveillance regime to attain and maintain a BHV1-free status as described by EU-legislation can be improved to reduce the monitoring costs without reduction of the system's sensitivity, given a within-herd design prevalence of 10%. The assessment of various surveillance designs could be highly useful to support decision-making towards a more risk-based approach of animal health surveillance.
10.1016/j.prevetmed.2016.12.003
pubmed_556_20480
BACKGROUND In recent years, phosphodiesterase type 5 (PDE5) inhibitors have been proposed for relieving the ureteral stent-related symptoms. We conducted a meta-analysis to assess the efficacy and safety of PDE5 inhibitors in the treatment of ureteral stent-related symptoms. METHODS Randomized controlled trials (RCTs) that reported on the effectiveness of PDE5 inhibitors on ureteral stent-related symptoms were identified and collected from Medline, Embase, and Cochrane Library databases. RESULTS Four RCTs involving 352 patients were included. Following treatment with PDE5 inhibitors for 1 week, significant improvement of urinary symptoms (P<0.00001) and sexual health (P=0.04) was observed in the PDE5 inhibitors group. After 3 weeks, we found that PDE5 inhibitors were effective in relieving urinary symptoms [mean difference (MD): -11.94, 95% confidence interval (CI): -22.58 to -1.3, P=0.03], body pain (MD: -5.38, 95% CI: -9.35 to -1.41, P=0.008), and improving sexual health (MD: -4.13, 95% CI: -5.07 to -3.19, P<0.00001), general health (MD: -3.92, 95% CI: -5.76 to -2.08, P<0.0001), and additional health (MD: -2.21, 95% CI: -4.03 to -0.40, P=0.02). With regards to work performance (MD: -2.25, 95% CI: -5.13 to -0.62, P=0.12), no significant differences were observed between the PDE5 inhibitors group and the placebo group. In terms of safety, there were no significant differences between these two groups in the incidence of gastrointestinal [odds ratio (OR): 1.25, 95% CI: 0.51 to 3.04, P=0.63], or respiratory (OR: 1.48, 95% CI: 0.50 to 4.44, P=0.48) complications. CONCLUSIONS PDE5 inhibitors were effective in relieving symptoms of patients undergoing ureteral stent placement, and do not increase the risk of complications.
10.21037/apm-20-1100
pubmed_920_10738
Food beverage consumption is a worldwide age-old practice. It is also a common run-through habit among the tribes of North Eastern parts of India. The food beverage group Jou is a traditionally fermented rice-based beverage by Bodo community of Assam, the largest plain tribe. It is not only consumed by Bodos on regular basis but also widely used in their socio-cultural activities. Joubidwi (JB, fermented product), Joufinai (JF, preserved product) and Jougwran (JG, distilled) are the three varieties of Jou. Herewith, it had been reported; the concentrations of metals such as Cd, Co, Cr, Cu, Fe, K, Mn, Na, Ni, Pb and Zn in the three varieties of Jou to make people aware about the possible health benefits as well as the risks associated with the consumption of Jou. The metal contents were estimated using ICP-OES after digesting the samples with 10:1 mixture of concentrated nitric and concentrated sulfuric acid. The estimated daily intakes (EDI) of metals from consumption of JB, JF and JG were also within the recommended daily allowances (RDA). From the estimated target hazard quotient (THQ) values, it was observed no health risk associated with the consumption of Jou; whereas total target hazard quotient (TTHQ) of Joufinai were associated with more health risks. Metal concentrations of all metals in Bodo beverages was lower in comparison with barely based and wheat based beverages.
10.1016/j.toxrep.2021.06.013
pubmed_1060_2729
Black infant mortality is one of the most serious and long-standing public health problems in the United States. This article reports the findings of a study of the family planning records of 1143 residents of a city with one of the highest black infant mortality rates. The importance of increased social work involvement in the federally funded family planning system and specific social work strategies are discussed as methods to reduce black infant mortality.
10.1300/j010v13n02_08
pubmed_139_208
beta-N-acetyl-D-glucosaminidase (NAGase) and lysozyme activity were studied in isolated parotid and submandibular saliva collected from five healthy individuals over a 3-wk period. During the first week, saliva samples were collected three times within one specified day (9 a.m., noon, 4 p.m.). Then for each of the following 2 wk, saliva was collected at 9 a.m. of the same day. NAGase activity was determined spectrophotometrically by using p-nitrophenyl-glycoside as substrate. Lysozyme activity was determined turbidimetrically by using Micrococcus lysodeikticus cells as substrate. NAGase and lysozyme were present in all samples of parotid and submandibular saliva. NAGase activity was generally higher in saliva samples collected in the morning and decreased during the day. There was considerable variation in NAGase activity and almost no variation in lysozyme activity in samples taken from the same person. NAGase activity was higher in parotid than in submandibular saliva while lysozyme activity was somewhat higher in submandibular saliva.
10.1111/j.1600-0722.1987.tb01834.x
pubmed_697_9334
Recent findings have extended the documentation of complex sociality to the Platyhelminthes, describing the existence of a reproductive division of labour involving a soldier caste among the parthenitae of trematode parasites. However, all species examined to date occupy high positions in trematode interspecific dominance hierarchies and belong to two closely related families, the Echinostomatidae and the Philophthalmidae (Superfamily Echinostomatoidea). Further, the two species documented as lacking soldiers also belong to the Echinostomatidae. Here, we examine four species of intermediate dominance, all belonging to the family Heterophyidae (Superfamily Opisthorchioidea): Euhaplorchis californiensis, Phocitremoides ovale, Pygidiopsoides spindalis and Stictodora hancocki, all of which infect the California horn snail, Cerithideopsis californica (=Cerithidea californica). We quantify morphology, distribution and behaviour of rediae from fully developed colonies. We also provide information on colony structure for three developing heterophyid colonies to better understand colony development. We discuss the implications of our findings, particularly with respect to how they suggest alternatives to the conclusions of other researchers concerning the nature of trematode sociality. Our analyses of morphological, distributional and behavioural patterns of developed colonies indicate that these heterophyid trematodes have a non-reproductive caste whose function is defence of the colony from invading trematodes. Hence, a soldier caste occurs for species lower in dominance hierarchies than previously known, and is present in at least two superfamilies of digenean trematodes, suggesting that selection for a soldier caste may be much more common among the Trematoda than previously recognised.
10.1016/j.ijpara.2016.10.003
pubmed_575_9046
: In the young generations with nitrous oxide abuse (N2O), featured electrophysiological response of the peripheral neuropathy caused by nitrous oxide remains to be defined.: Patients with nitrous oxide abuse (20 cases), two variants of Guillain-Barré syndrome (GBS), that is, acute inflammatory demyelinating polyradiculoneuropathy (GBS-AIDP, 19 cases) and acute motor axonal neuropathy (GBS-AMAN, 18 cases), as well as diabetic peripheral neuropathy (DPN, 20 cases) were enrolled into this study. Electrophysiological parameters including distal motor latency (DML), motor nerve conduction velocity (MNCV), sensory nerve conduction velocity (SNCV), amplitudes of compound muscle action potential (CMAP), and sensory nerve action potential (SNAP) were measured and analyzed by comparing the parameters between the aforementioned patients groups as well as normal control group (20 subjects).: Compared to normal control subjects, patients with nitrous oxide abuse showed prolonged DML, slower MNCV and SNCV in the limbs, lower amplitudes of CMAP in the median, tibial and peroneal nerves, and lower SNAP in median and ulnar nerves. Abnormalities of MNCV and amplitudes of CMAP in the lower limbs were significantly higher than that in the upper limbs . Abnormal electrophysiological features of patients with nitrous oxide abuse were dramatically different from those in GBS-AIDP or DPN patients, but similar to those in GBS-AMAN patients.: Nitrous oxide abuse could cause abnormal electrophysiological response in the limbs. Some of the parameters (DML, MNCV, SNCV, CMAP and SNAP) appeared significantly different between the patients with nitrous oxide abuse, GBS with AIDP or AMAN, and DPN patients.Significance: Electrophysiological examination could be considered as an important supporting factor in differential diagnosis for nitrous oxide abuse, GBS with AIDP or AMAN, and DPN.
10.1080/01616412.2021.1935101
pubmed_725_7646
A species of Aspergillus was isolated from vomitus and scrapings of the tongue of a patient with a form of respiratory illness. The fungus has since been identified as Aspergillus aculeatus, Iizuka. The fungus grew over a wide range of temperatures, the spores appeared to be thermophilic. Many local foodstuffs supported the growth of the fungus in culture. Ultraviolet light inhibited mycelia growth and sporulation of A. aculeatus. The fungicides brestan, benlate, fundazole and kocide 101 inhibited the growth of the fungus more than daconil, demosen and dithane M-45. Amphotericin B and sulfadiazine completely arrested the growth of the fungus while sulfamycin, nalidixic acid and kanamycin had no detectable effects.
pubmed_725_7646
pubmed_940_22282
Occupational exposures to blood-borne pathogens occur regularly in diverse settings and involve multiple groups of healthcare workers. Current compliance of healthcare workers with behavioral controls is poor, and additional engineering and work-practice controls for exposure prevention are inadequate and/or underutilized. Barriers to effective postexposure management include deficient knowledge and fear and denial among healthcare workers, the diverse risks associated with different exposures, the costs and personnel necessary for providing exposure management 24 hours a day, variable levels of expertise in postexposure prophylaxis strategies, and administrative requirements for standardized policies and procedures. In the current environment, healthcare institutions are largely ill equipped to provide timely and effective postexposure prophylaxis. Widespread worker education, simplified reporting mechanisms, and availability of prompt source and worker testing along with timely, free postexposure prophylaxis is central to an institution's postexposure program. Postexposure management programs should be comprehensive and provide standardized procedures, expand workers' access to postexposure prophylaxis by establishing responsible parties in diverse areas, disseminate program information to all workers, and ensure confidentiality in the care and follow-up of exposed workers. To implement such programs, it may be necessary to merge resources and link local management of exposures with regional expertise to provide up-to-date counseling in a rapidly changing field. Careful surveillance of occupational exposures is essential to evaluate program efficacy, direct prevention efforts, and to determine necessary resources to ensure continued successful delivery of postexposure prophylaxis.
10.1016/s0002-9343(97)00070-3
pubmed_303_1479
The lethal response of Chinese hamster cells heated to 42 degrees was determined following 0 to 30 hr culturing under hypoxic conditions. Oxygenated and acutely hypoxic cells were equally sensitive to hyperthermia; however, sensitivity increased with the time of culturing under hypoxic conditions prior to treatment. Three hr at 42 degrees resulted in a surviving fraction of approximately or equal to 0.1 under acute hypoxic conditions and less than 0.001 for cells cultured for 30 hr under oxygen-deprived conditions before the heat treatment. The increased sensitivity to hyperthermia was was due in part to a decrease in the pH of the medium which occurred as a result of cell metabolism; this could be reversed by increasing pH to 7.3 immediately prior to heat treatment. However, even under fully controlled pH conditions, prolonged oxygen deprivation increased hyperthermic cell killing by a factor of approximately or equal to 5. This effect was not reversed by returning the cells to normal oxygen tension prior to treatment. These data demonstrate that tumorlike microenvironmental conditions (reduced O2 tension and pH) substantially increase the sensitivity of cells to 42 degrees hyperthermia.
pubmed_303_1479
pubmed_690_19373
Mesenteric lymph chylomicrons were characterized during and after the establishment of steady-state triglyceride transport. Chylomicrons were isolated from lymph at 0, 2, 4, 6, 8 and 12 h after the start of an 8-h infusion of triglyceride emulsion (prepared using either corn or butter oil) at 160 mumol/(kg.h). Lymph flow was not influenced by triglyceride source. Output of triglyceride, measured both in whole lymph and in the chylomicron fraction, was not significantly affected by triglyceride source. Butter oil infusion produced a higher output of chylomicron phospholipid and unesterified cholesterol than was observed in response to corn oil emulsion. Ratios of transported phospholipid to triglyceride for butter oil chylomicrons were higher (1.3- to 1.7-fold) than those for corn oil chylomicrons at every time point examined after the start of lipid infusion. No other compositional differences in chylomicrons due to triglyceride source were observed. These results support the hypothesis that differences in efficiency of absorption and transport between saturated and unsaturated fat are sufficient to explain size differences in secreted chylomicrons in response to corn and butter oil infusions, and suggest that chylomicron number may be influenced by dietary fat saturation.
10.1093/jn/122.8.1634
pubmed_39_19093
BACKGROUND Regorafenib is a multi-targeted tyrosine kinase inhibitor approved for use in refractory colorectal cancer. We report the first case of seizures secondary to acute liver failure, shortly after initiation of regorafenib in a patient with advanced rectal carcinoma. CASE PRESENTATION A 64 year-old Caucasian female presented with confusion and generalized tonic-clonic seizures, 5 days after initiation of regorafenib for advanced rectal cancer. Investigations revealed significant elevations in bilirubin and alanine aminotransferase. No other cause for seizures and liver dysfunction were found. After interruption of regorafenib, no further seizures occurred, the symptoms of confusion resolved and liver function returned to normal. CONCLUSIONS We report the first case of regorafenib-induced acute liver failure resulting in seizures. We suggest early monitoring for side effects, both clinically and biochemically after initiation of regorafenib.
10.1186/s13104-015-1502-4
pubmed_976_17772
This research proposes a new theory of direct causation and examines how this concept plays a key role in the linguistic coding and individuation of causal events. According to the no-intervening-cause hypothesis, a causal chain can be described by a single-clause sentence and construed as a single event if there are no intervening causers between the initial causer and the final causee. Consistent with this hypothesis, participants used single-clause sentences (lexical causatives) more often than two-clause sentences (e.g. periphrastic causatives) for causal chains in which (1) the causer and causee touched (Experiments 1 and 2), and (2) an intervening entity could be construed as an enabling condition rather than another cause (Experiments 2-4). In addition, event judgments paralleled linguistic descriptions: chains that could be described with single-clause expressions were more often construed as single events than chains that could not (Experiments 1-3). Implications for languages other than English, for the linguistic coding of accidental outcomes and for the relationship between cognition and language in general are discussed.
10.1016/s0010-0277(03)00004-0
pubmed_323_24589
BACKGROUND A large proportion of patients with acute myeloid leukemia (AML) are not fit for intensive and potentially curative therapy due to advanced age or comorbidity. Previous studies have demonstrated that a subset of these patients can benefit from disease-stabilizing therapy based on all-trans retinoic acid (ATRA) and valproic acid. Even though complete hematological remission is only achieved for exceptional patients, a relatively large subset of patients respond to this treatment with stabilization of normal peripheral blood cell counts. METHODS In this clinical study we investigated the efficiency and safety of combining (i) continuous administration of valproic acid with (ii) intermittent oral ATRA treatment (21.5 mg/m2 twice daily) for 14 days and low-dose cytarabine (10 mg/m2 daily) for 10 days administered subcutaneously. If cytarabine could not control hyperleukocytosis it was replaced by hydroxyurea or 6-mercaptopurin to keep the peripheral blood blast count below 50 × 109/L. RESULTS The study included 36 AML patients (median age 77 years, range 48 to 90 years) unfit for conventional intensive chemotherapy; 11 patients responded to the treatment according to the myelodysplastic syndrome (MDS) response criteria and two of these responders achieved complete hematological remission. The most common response to treatment was increased and stabilized platelet counts. The responder patients had a median survival of 171 days (range 102 to > 574 days) and they could spend most of this time outside hospital, whereas the nonresponders had a median survival of 33 days (range 8 to 149 days). The valproic acid serum levels did not differ between responder and nonresponder patients and the treatment was associated with a decrease in the level of circulating regulatory T cells. CONCLUSION Treatment with continuous valproic acid and intermittent ATRA plus low-dose cytarabine has a low frequency of side effects and complete hematological remission is seen for a small minority of patients. However, disease stabilization is seen for a subset of AML patients unfit for conventional intensive chemotherapy.
10.1186/1868-7083-5-13
pubmed_65_13685
Long-term antiepileptic drug (AED) treatment is the standard therapy for epilepsies. In about 60% of patients, the first AED tried usually leads to seizure control. After failure of the first AED, it is important to achieve seizure control rapidly and without side effects. Combining the first drug with an add-on drug appears to be more effective than a second monotherapy. However, no scientifically based data are available that favor any particular drug combination. Along with pharmacokinetic considerations, clinical experience is an important determinant in choosing a second AED for use as an add-on. The time needed to introduce a particular AED is a further consideration. The simultaneous introduction of two add-on drugs, one requiring slow titration and one permitting rapid introduction, may be a useful strategy. If the quickly introduced drug is effective as an add-on, introduction of a slowly titrated second add-on can be obviated. If the quickly introduced drug reduces seizure frequency, the patient's quality of life is improved during titration of the second add-on. If the second, slowly titrated drug is more effective than the quickly introduced one, the less-effective drug can be withdrawn. This strategy also allows a direct comparison between two add-on drugs at the same time.
10.1111/j.1528-1157.1999.tb00926.x
pubmed_101_26016
BACKGROUND The African violets are endangered plant species restricted mainly to the Eastern Arc Mountains biodiversity hotspots in Kenya and Tanzania. These plants grow well in shaded environments with high humidity. Given their restricted geographical range and published evidence of dependance on insect vectors to facilitate sexual reproduction, understanding their pollination biology is vital for their survival. METHODS We conducted an empirical study using flower visitor observations, pan trapping and bagging experiments to establish the role of flower visitors in the fruit set of a locally endemic and critically endangered species of African violet in Taita Hills, Kenya, Streptocarpus teitensis. RESULTS The study found that fruit set is increased by 47.8% in S. teitensis when flowers are visited by insects. However, it is important to note the presence of putative autogamy suggesting S. teitensis could have a mixed breeding system involving self-pollination and cross-pollination since bagged flowers produced 26.9% fruit set. CONCLUSIONS Insects appear to be essential flower visitors necessary for increased fruit set in S. teitensis. However, there is evidence of a mixed breeding system involving putative self-pollination and cross-pollination suggesting that S. teitensis is somewhat shielded from the negative effects of pollinator losses. Consequently, S. teitensis appears to be protected to a degree from the risks such as reproduction failure associated with pollinator losses by the presence of a safety net in putative self-pollination.
10.7717/peerj.10473
pubmed_1141_5430
OBJECTIVE To evaluate the safety and long-term efficacy of curative-intent radiation therapy in patients with apparently localized prostate cancer. METHOD 48 patients with T < 3 M0 prostate cancer recruited between 1981 and 1985 received regular clinical follow-up for at least ten years or until their death. Radiation therapy was given according to the protocols established by Ray and Bagshaw. RESULTS Radiation therapy was safe and effective in most patients. The rate of escape phenomenon was less than 10% after two years. Tumor control rates were greater than 80% after five years and 50% after ten years. Unfortunately, local remission, even when prolonged, did not necessarily indicate a complete cure: 20% of local recurrences developed five to 11 years after radiation therapy. CONCLUSION Radiation therapy may be the best first-line treatment in men older than 75 years of age and in those whose life expectancy seems shorter than ten years, but should probably not be considered curative.
pubmed_1141_5430
pubmed_68_17824
Four squirrel monkeys responded daily under a fixed-interval 5-min or 8-min schedule of food-pellet delivery. Cocaine (0.03 to 1.7 mg/kg) and saline were injected before occasional daily sessions (acute administration). Some doses of cocaine produced substantial overall increases in response rate for 3 of the subjects; effects were less substantial for the remaining subject, who exhibited modest increases in response rate early in the session and during the middle portion of the intervals. A dose that increased response rate when administered acutely was then administered before each session (chronic administration). Chronic administration resulted in a reduction in the increases in response rate seen under acute administration for all subjects.
10.1901/jeab.1994.62-45
pubmed_109_9102
Serum MIF activity was studied in ten patients with sarcoidosis, fourteen with granuloma annulare, four with necrobiosis lipoidica, and nine with various dermatological diseases. Positive MIF activity was found in the sera of nine of the ten patients with sarcoidosis and eleven of the fourteen patients with granuloma annulare. The delayed hypersensitivity tests were negative in all nine of the patients with sarcoidosis who had serum MIF activity and were positive in only three patients with cutaneous sarcoid lesions. One of four patients with necrobiosis lipoidica demonstrated minimal serum MIF activity. Data on serum lymphokine activity in sarcoidosis and granuloma annulare suggest that these two diseases are related to delayed hypersensitivity mechanisms.
10.1111/j.1365-2133.1976.tb00857.x
pubmed_544_171
The initiator tRNA, methionyl-tRNA(i) (Met), of yeast and wheat germ forms relatively unstable ternary complexes with their corresponding elongation factors T and GTP. Such complexes can be demonstrated only with fast separation techniques such as Sephadex G-50 and Millipore filtration, but not with the slow Sephadex G-100 method, although both techniques yield stable ternary complexes with all other aminoacyl-tRNAs, including the internal Met-tRNA(m) (Met). To bind yeast-initiating Met-tRNA(i) (Met) to ribosomes, initiation factors present in a ribosomal wash fraction from yeast are needed.
10.1073/pnas.68.8.1805
pubmed_174_3285
We have used a sporozoite neutralization assay to define the biological relevance of the cross-reactivity of two monoclonal antibodies, raised against sporozoites of the human parasite Plasmodium malariae (Uganda 1/CDC), with sporozoites of the simian parasite Plasmodium brasilianum (Colombian). In vitro incubation of each of these two monoclonal antibodies with sporozoites of P. brasilianum totally abolished the infectivity of these parasites for Saimiri sciureus. Using Western blot analysis and one of the P. malariae monoclonal antibodies, we identified two sporozoite proteins characteristic of the Colombian isolate of P. brasilianum with apparent molecular weights of 56,000 and 66,000. The same monoclonal antibody identified two proteins in an extract of the Peruvian isolate of P. brasilianum with apparent molecular weights of 59,000 and 69,000.
10.1128/iai.50.1.58-61.1985