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pubmed_388_12510 | An investigation was made into the effect of Corynebacterium parvum therapy on cerebral tumours in mice. I.v. C. parvum caused a slight but significant increase in the survival of BALB/c mice injected intracerebrally (i.c.) with not more than 50 Meth A cells. C. parvum was most effective if given on the same day or 5 days after tumour. If this interval was increased there was no effect. Multiple i.v. injections were no more effective than a single dose. I.v. C. parvum had no influence on the survival of C57BL mice injected i.c. with Lewis tumour cells, and had little effect on the induction of i.c. or s.c. tumours by methylcholanthrene. It was concluded that C. parvum therapy was of little use in the treatment of cerebral tumour in mice. The clinical implications of these findings are discussed. | 10.1038/bjc.1977.63 |
pubmed_417_21082 | The acute blockade of spinal glycinergic inhibition with intrathecal strychnine (i.t. STR; a glycine antagonist) in rats induces a change in somatosensory processing which is very similar to the sensory dysesthesia of clinical neural injury pain. In the present study, the effects of i.t. STR were examined in urethane-anesthetized rats. Noxious paw pinch (PP) or tail immersion (TI) in 55 degree C water evoked a pronounced pressor response, increased heart rate (HR) and desynchronized the electroencephalogram; a non-noxious, hair deflection (HD) elicited only minor cardiovascular responses. After i.t. STR (40 micrograms), an identical HD stimulus evoked markedly enhanced cardiovascular responses, resembling those evoked by noxious stimuli, and a HD-evoked motor withdrawal was observed. Consistent STR-dependent responses were only observed if a light plane of anesthesia was maintained for the duration of the experiment. The effects of i.t. STR were dose-dependent and reversible, lasting 15-30 min. Spinal morphine (50 micrograms) completely abolished the cardiovascular responses to PP and TI, but the HD-evoked, STR-dependent cardiovascular and motor withdrawal responses remained unchanged. In contrast, the non-selective excitatory amino acid antagonist, gamma-D-glutamylglycine (DGG; 50 micrograms) was effective in suppressing both the STR-dependent cardiovascular and motor withdrawal responses. These data suggest that STR-dependent responses evoked by non-noxious stimuli are mediated by mechanisms distinct from those of conventional noxious stimuli and that i.t. STR may be useful for investigating the spinal pharmacology of somatosensory processing following the loss of spinal glycinergic inhibition. | 10.1016/0304-3959(94)90146-5 |
pubmed_226_7799 | OBJECTIVES
To investigate the changes of T helper cell (Th)1/Th2-related cytokine expression in the saliva of minor recurrent aphthous stomatitis (RAS) patients before and after treatment with systemic prednisone.
METHODS
A total of 101 patients with RAS and 15 participants with normal oral mucosa as controls were enrolled in this study. The levels of cytokine expression in the whole unstimulated saliva were examined using a multiplex bead-based cytometric bead array before and after prednisone treatment at a starting dose of 15 mg/day.
RESULTS
The levels of salivary interleukin (IL)-4, IL-5, IL-6, IL-10, interferon (IFN)-γ, and tumor necrosis factor-α (TNF-α) in RAS patients were significantly higher than those of the normal controls (all P < 0.001). Importantly, the levels of salivary IL-6, IL-10, IFN-γ, and TNF-α in RAS patients were significantly decreased following prednisone treatment (all P < 0.001). Moreover, the IFN-γ to IL-4 ratio (mean: 26.9) was significantly (P < 0.001) decreased after treatment, which almost returned to normal (mean: 24.4; P > 0.05).
CONCLUSION
This preliminary study demonstrates for the first time that prednisone exerts a significant therapeutic role against RAS through decreasing salivary cytokine levels and promoting a Th1/Th2 balance.
CLINICAL RELEVANCE
Salivary cytokine profiles may provide a noninvasive, convenient, and effective approach to monitoring the course of RAS and may even be helpful to identify key pathogenic factors and potential mechanisms. | 10.1007/s00784-021-04349-x |
pubmed_596_7845 | Babesiosis is caused by a protozoan parasite of the genus Babesia. In the United States, the usual infective organism Babesia microti, is most commonly transmitted through the bite of an infected Ixodestick. While the majority of patients exhibit sub-clinical signs and symptoms, significant illness can result. Spontaneous splenic rupture is a life-threatening complication of some viral and protozoan infections. We present a case of Babesiosis with spontaneous splenic rupture in which conservative management with blood transfusions and hospital-based care were successful, and the patient was spared splenectomy. To our knowledge, this is the first reported case treated without splenectomy. Our successful experience suggests conservative management may be appropriate for some patients. | pubmed_596_7845 |
pubmed_195_2785 | Previous studies have suggested that obstructive sleep apnea (OSA) may be a risk factor for stroke. In this study, we assessed that OSA is an independent risk factor of silent cerebral infarction (SCI) in the general population, and in a non-obese population. This study recruited a total of 746 participants (252 men and 494 women) aged 50-79 years as part of the Korean Genome and Epidemiology Study (KoGES); they underwent polysomnography, brain magnetic resonance imaging and health screening examinations. SCI was assessed by subtypes and brain regions, and lacunar infarction represented lesions <15 mm in size in the penetrating arteries. Moderate-severe OSA was determined by apnea-hypopnea index ≥15. The results indicated that 12.06% had moderate-severe OSA, 7.64% of participants had SCI and 4.96% had lacunar infarction. Moderate-severe OSA was associated positively with SCI [odds ratio (OR): 2.44, 95% confidence interval (CI): 1.03-5.80] and lacunar infarction (OR: 3.48, 95% CI: 1.31-9.23) in the age ≥65-year group compared with those with non-OSA. Additionally, in the basal ganglia, OSA was associated with an increase in the odds for SCI and lacunar infarction in all age groups, and especially in the ≥65-year age group. In the non-obese participants, OSA was also associated positively with SCI in the ≥65-year age group, lacunar infarction in all age groups, and especially in the ≥65-year age group. There was also a positive association with the basal ganglia. Moderate-severe OSA was associated positively with SCI and lacunar infarction in elderly participants. Treatment of OSA may reduce new first-time cerebrovascular events and recurrences. | 10.1111/jsr.12034 |
pubmed_826_14102 | Ambient air polycyclic aromatic hydrocarbon (PAH) samples were collected at traffic, residential, coastal, and semiurban sites in Bursa, Turkey, between June 2008 and June 2009. For the traffic, residential, coastal, and semiurban sites, the average gas phase total PAH (∑12PAH) concentrations were 113 ± 131, 142 ± 204, 53 ± 73, and 19 ± 34 ng/m(3), respectively, whereas the average particle phase total PAH concentrations were 28 ± 36, 56 ± 85, 24 ± 40, and 11 ± 23 ng/m(3), respectively. Phenanthrene and fluoranthene had the highest concentrations of all of the sampling sites in the gas phase. The PAH concentrations in the heating period were 5-7 times greater than the nonheating period concentrations. Principal component analysis (PCA) was used to investigate the relationship between the levels of PAHs determined in ambient samples and their possible sources. The PCA model shows that coal combustion and vehicle emissions affected PAH emissions. Moreover, the molecular diagnostic ratios indicated that coal-burning and traffic emissions were the dominant PAH sources. The multiple linear regression analysis indicated that the meteorological parameters also affected the ambient PAH concentrations. The sampling site characteristics, meteorological conditions, dispersion, and local sources all affected the concentration levels. | 10.1007/s00244-014-0105-8 |
pubmed_581_13703 | Platycodon grandiflorum root is a traditional medicine and food material rich in triterpenoid saponins. Its major constituent, platycodin D (PD), is known to have various pharmacological properties, but processing methods may influence the PD content. In this study, a fully validated HPLC-ELSD method was developed for the quantification of PD in various states of 73 P. grandiflorum root samples from East Asia, and it exhibited a marked variation of the content. Furthermore, the effects of processing procedures such as peeling and drying temperature on the PD content were investigated using UPLC-ELSD analysis, and as a result, a significant influence of processing methods such as peeling and heating of samples on the content was confirmed. Specifically, unpeeled samples that were dried at 40 °C showed the greatest PD content. The obtained results could facilitate the reliable standardization of P. grandiflorum for precise authentication and efficacious applications. | 10.1007/s12272-017-0946-6 |
pubmed_834_20286 | We present a case of primary carcinoma of the vulva successfully treated with local excision and ipsilateral groin dissection. Eleven cases of this entity have been reported in the world literature since 1936. We review the literature and offer guidelines regarding morphologic and immunohistochemical criteria for diagnosis and primary and adjuvant treatment for this rare condition. | 10.1006/gyno.1995.1080 |
pubmed_629_15223 | It was the aim of the present study to investigate chloride secretion across the proximal colon of Cftr (TgH(neoim)1Hgu) congenic mice. Stripped epithelia were incubated in Ussing chambers and the electrophysiological data were compared between cystic fibrosis (CF) animals and wild type (WT) animals. In comparison with the control animals, all Cftr (TgH(neoim)1Hgu) congenic mice had a distinctly reduced basal chloride secretion and a reduced chloride secretion after stimulation with carbachol and forskolin. When comparing chloride secretion across the proximal colon between WT animals, all mice showed a comparable pattern of response to carbachol and forskolin but quantitative differences, BALB/c exhibiting the highest and HsdOla:MF1 exhibiting the lowest increase in Cl current. Likewise, all CF animals showed the same reaction pattern to carbachol and forskolin, but there was no distinct difference that lasted for the whole measurement. To investigate interferences between Ca- and cyclic adenosine monophosphate-activated pathways of Cl secretion in CF animals, we studied epithelia from CF/3CF/1F1 animals with a mixed background. In these animals, the levels of the carbachol or forskolin-induced chloride currents did not depend on the prestimulation with the respective other secretagogue. 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid, which blocks calcium-activated chloride channels, reduced the current response to carbachol by about 23%. This result, obtained in BALB/c-Cftr (TgH(neoim)1Hgu) mice, indicates that alternative chloride channels might be present in the proximal colon of these mice. In contrast, there was no evidence for alternative chloride conductances in BALB/c WT animals, but we cannot exclude that in WT mice a higher chloride secretion via Cftr-channels may have masked an alternative chloride secretion. | 10.1007/s00360-006-0109-4 |
pubmed_815_7396 | People sometimes fantasize entire complex scenarios and later define these experiences as memories of actual events rather than as imaginings. This article examines research associated with three such phenomena: past-life experiences, UFO alien contact and abduction, and memory reports of childhood ritual satanic abuse. In each case, elicitation of the fantasy events is frequently associated with hypnotic procedures and structured interviews which provide strong and repeated demands for the requisite experiences, and which then legitimate the experiences as "real memories." Research associated with these phenomena supports the hypothesis that recall is reconstructive and organized in terms of current expectations and beliefs. | 10.1080/00207149408409369 |
pubmed_1122_2083 | We investigated the correlation between tumor sensitivity to 5-fluorouracil (5-FU) and the enzymatic activity and mRNA levels of thymidylate synthetase (TS) and dihydropyrimidine dehydrogenase (DPD) using human tumor xenografts in nude mice. Three gastric carcinoma xenografts (SC-1-NU, St-4, and H-111), two colon carcinoma xenografts (Co-4 and Col-3-JCK), one pancreatic carcinoma xenograft (PAN-3-JCK), and one breast carcinoma xenograft (MX-1) were inoculated into nude mice. When the resultant tumors reached 100-300 mg, 5-FU was administered i.p. at a dose of 60 mg/kg in a schedule of three times every 4 days, and the antitumor activity of 5-FU was evaluated as the relative mean tumor weight in treated mice compared to control mice. Xenografts were also inoculated into untreated nude mice. When tumors weighed 200-300 mg, tumor tissues were resected for measurement of tumoral TS and DPD. TS and DPD activities were detected by the TS-binding assay and a radioenzymatic assay, respectively. mRNA levels were measured by semiquantitative reverse transcription-PCR, with glyceraldehyde-3-phosphate dehydrogenase coamplified as an internal standard. TS and DPD activities ranged from 84.7 to 775.5 fmol/mg protein and from not detectable to 79.7 pmol/min/mg protein, respectively. TS and DPD mRNA levels ranged from 0.51 to 9.90 and from not detectable to 0.93, respectively. The enzymatic activities of TS and DPD were correlated with observed mRNA levels. DPD levels were significantly correlated with 5-FU sensitivity, with high DPD activity and high DPD mRNA level resulting in low sensitivity to 5-FU. In contrast, no correlation between TS level and 5-FU sensitivity was observed. Tumoral DPD activity and DPD mRNA level may be useful indicators in predicting the antitumor activity of 5-FU. | pubmed_1122_2083 |
pubmed_746_6156 | OBJECTIVES
To determine whether the medical prescription of testosterone gel can successfully increase facial hairs in young men with beta-thalassemia major.
METHODS
Thirty-two men with beta-thalassemia major, at least 15 years old (tanner stage 4), were randomized in four blocks according to age and serum testosterone level. The cases received 2.5% testosterone gel. The changes in the number of terminal hairs were evaluated by a dermatologist after 6 months. Student's t-test and paired t-test were used to compare the results.
RESULTS
The serum testosterone levels of controls and cases were 9.5+/-5.7 (mean+/-SD) and 10.5+/-9.6 ng/l, respectively. The number of terminal hairs (per cm2) in cases (29.8+/-13.6) was significantly higher than that for controls (13.9+/-13.2) (p<0.005). One patient from each group complained of a sense of irritation.
CONCLUSION
The 2.5% testosterone gel was effective and well tolerated in inducing the transformation of the terminal hairs of the beard area of thalassemic males. | 10.1080/09546630701567378 |
pubmed_879_23373 | Rift Valley fever virus (RVFV) belongs to the order Bunyavirales and is the type species of genus Phlebovirus, which accounts for over 50% of family Phenuiviridae species. RVFV is mosquito-borne and causes severe diseases in both humans and livestock, and consists of three segments (S, M, L) in the genome. The L segment encodes an RNA-dependent RNA polymerase (RdRp, L protein) that is responsible for facilitating the replication and transcription of the virus. It is essential for the virus and has multiple drug targets. Here, we established an expression system and purification procedures for full-length L protein, which is composed of an endonuclease domain, RdRp domain, and cap-binding domain. A cryo-EM L protein structure was reported at 3.6 Å resolution. In this first L protein structure of genus Phlebovirus, the priming loop of RVFV L protein is distinctly different from those of other L proteins and undergoes large movements related to its replication role. Structural and biochemical analyses indicate that a single template can induce initiation of RNA synthesis, which is notably enhanced by 5' viral RNA. These findings help advance our understanding of the mechanism of RNA synthesis and provide an important basis for developing antiviral inhibitors. IMPORTANCE The zoonosis RVF virus (RVFV) is one of the most serious arbovirus threats to both human and animal health. RNA-dependent RNA polymerase (RdRp) is a multifunctional enzyme catalyzing genome replication as well as viral transcription, so the RdRp is essential for studying the virus and has multiple drug targets. In our study, we report the structure of RVFV L protein at 3.6 Å resolution by cryo-EM. This is the first L protein structure of genus Phlebovirus. Strikingly, a single template can initiate RNA replication. The structure and assays provide a comprehensive and in-depth understanding of the catalytic and substrate recognition mechanism of RdRp. | 10.1128/JVI.01713-21 |
pubmed_1069_17633 | BACKGROUND
The action spectrum of solar urticaria varies among cases. In addition, light spectra outside the activating wavelengths can influence the wheal formation in selected patients.
OBJECTIVE
To know the mechanisms of light energy, we examined the effect of wavelengths on the skin and the serum factor.
METHODS
The patient's skin and serum were exposed to artificial light sources, in vivo and in vitro, respectively.
RESULTS
The action spectrum ranged from UVA to visible light (approximately 480 nm). The exposure to longer wavelengths immediately after the exposure inhibited the development of urticaria. Conversely, the irradiation of longer wavelengths before exposure increased the wheal formation. Furthermore, UVB irradiation prior to the exposure of urticaria-eliciting light also increased the urticarial reaction, while postirradiation of UVB had no effect. The patient developed an urticarial wheal at the site of injection of her own serum, which had been previously exposed to the action spectrum in vitro. Preirradiation increased the production of the photosensitizer, while postirradiation revealed no effect. Ultrafiltration techniques showed that the molecular weight of the photosensitizer is more than 300 kD.
CONCLUSION
We detected action, inhibition and augmentation spectra in a patient with a severe solar urticaria. Various wavelengths influence the wheal-forming factor in complex interactions. | 10.1159/000246570 |
pubmed_960_6372 | Europium-154 can be obtained as a by-product from the large-scale production of Samarium-153 and possesses attractive features (t1/2 8.592 yr; Egamma 0.12-1.6 MeV) for use as a reference source similar to 152Eu (t1/2 13.516 yr; Egamma 0.12-1.4 MeV), which is the gold standard for calibration in gamma ray spectrometry. Thermal neutron irradiation of 5mg of 98% enriched 153Sm2O3 target in the reactor led to approximately 200 GBq 153Sm and 1.26 MBq 154Eu. A typical batch control sample of 153SmCl3 solution and final radiopharmaceutical product formulation of 153Sm-phosphonate (153Sm-EDTMP) pooled together contained about 20% of total yield, requiring post decay disposal of 153Sm as radioactive waste. Such spent solutions pooled on quarterly basis led to availing 756 kBq of 154Eu. The radioactivity content and radionuclide purity (approximately 82%) of the recovered 154Eu sample were envisaged as adequate to prepare reference sources for calibration of gamma ray spectrometers. At present, one batch of 153Sm is handled per month at our institution, with the possibility for weekly processing in future. Access to approximately 3.5 MBq of 154Eu on quarterly basis is envisaged, apart from obviating the need for instituting steps to tackle disposal of the long-lived 154Eu in the spent solution. Up to 60-120 units of 20-100 kBq of 154Eu reference sources per year could thus be available by the proposed strategy. | 10.1016/j.apradiso.2004.04.019 |
pubmed_623_23187 | PURPOSE
The purpose of this analysis was to assess the utility of Pitx2+/- mice as a model for the ocular features of Axenfeld-Rieger Syndrome and for congenital glaucoma.
METHODS
Eyes of Pitx2+/- and wild-type littermates were examined clinically using optical coherence tomography (OCT) and fundus photography. Intraocular pressures were measured using a TonoLab rebound tonometer. Eyes were examined histologically to assess PITX2 expression, structural integrity, and optic nerve and ganglion cell content.
RESULTS
PITX2 is present postnatally in the corneal endothelium and stroma, iris stroma, trabecular meshwork, and Schlemm's canal. Reduced central corneal thickness, iris defects, and iridicorneal adhesions are all prevalent in Pitx2+/- eyes. Although optic nerve heads appear normal at postnatal day 7, IOP is elevated and optic nerve head cupping is fully penetrant in Pitx2+/- eyes by 3 weeks of age. Neurodegeneration is present in a significant percentage of optic nerves from Pitx2+/- mice by 3 weeks of age, and is fully penetrant by 2 months of age. Pitx2+/- eyes show significant reductions in specifically ganglion cell density in all four quadrants by 2 months of age.
CONCLUSIONS
Pitx2+/- mice model the major ocular features of Axenfeld-Rieger Syndrome and will be an important resource for understanding the molecular mechanisms leading to anterior segment dysgenesis and a high prevalence of glaucoma in this disease. In addition, these mice may provide an efficient new model for assessing the molecular events in glaucoma more generally, and for developing and testing new treatment paradigms for this disease. | 10.1167/iovs.16-19700 |
pubmed_684_1595 | We have designed and synthesized a gene encoding a fusion protein comprising Magainin2 and a carrier protein with the aim of screening for a suitable carrier protein expressing antibacterial peptides in the mammalian expression system. The antibacterial peptide Magainin2 was used as a model. Our results on mammalian cell expression showed that there was no exceptional splicing in the transfected CHO-s cells. Analysis of the transgenic mouse model revealed that the expression level of this fusion protein in one transgenic positive mouse was up to 10 g/l, which is close to the level of beta-casein in goat milk. The bioactivity analysis showed that the digested fusion protein had antibacterial activity. These results demonstrate that the synthetic gene of the carrier protein is suitable for expressing an antibacterial peptide in a mammalian cell system at high productivity and efficiency. Moreover, they demonstrate the potential for producing antibacterial peptides in a transgenic animal bioreactor on a large scale and inexpensively. | 10.1007/s11248-008-9221-4 |
pubmed_546_12988 | OBJECTIVE
The development of an experimental peritoneal dialysis (PD) model in rabbits to investigate peritoneal transport characteristics during a longitudinal follow-up and to assess normal values of these peritoneal transport parameters.
DESIGN
Peritoneal transport parameters were determined in conscious, unrestrained rabbits by standard peritoneal permeability analysis adjusted for rabbits (SPAR). In this test a 1-hour dwell with 3.86% glucose dialysate is used. Dextran 70 (1g/L) was added to the dialysate to allow calculation of fluid kinetics. Dialysate samples were taken before, 10, and 40 minutes after instillation and at the end of the dwell. Blood was drawn at the end of the dwell.
EXPERIMENTAL ANIMALS
Eighteen female New Zealand White rabbits (2565 g) were included for catheter implantation. SPARs were performed in 15 animals; the other 3 were excluded due to complications.
MAIN OUTCOME
The mass transfer area coefficients (MTACs) of the low molecular weight solutes urea (MTAC(urea)) and creatinine (MTACcr) were calculated. The clearances of albumin (CIalb) and IgG (CI(IgG)), glucose absorption, and fluid transport were computed. Coefficients of intraindividual variation (Vc) were calculated for these parameters.
RESULTS
The main complications were catheter obstruction and/or dislocation. Five rabbits underwent uncomplicated PD during a 4-week period. Fifteen SPARs in 15 stable rabbits were performed and analyzed to obtain normal values. Means and standard deviations of the transport parameters were as follows: MTAC(urea) 2.24+/-0.57 mL/min, MTACcr 1.61+/-0.30 mU/min, CI(alb) 52.9+/-17.2 microL/min, CI(IgG) 44.5+/-22.9 UL/min. The transcapillary ultrafiltration rate was 0.66+/-0.13 mL/min and the lymphatic absorption rate 0.47+/-0.26 mL/min. The parameters of solute transport were upscaled to those in humans using two different methods. MTACs of low molecular weight solutes in rabbits and patients were of the same order of magnitude, but the clearance of albumin was approximately four times higher in rabbits than in patients, and that of IgG eight times. In all rabbits sieving of sodium was observed. The dialysate/plasma (D/P) of sodium decreased to a minimum at 40 min (p<0.003 vs the initial value), followed by a rise to 60 min. The minimal value was 0.884+/-0.002. The coefficients of variation calculated on 7 rabbits that underwent two or more SPARs were similar to those assessed from the patient data. This indicates stability of the model and reproducibility of the SPAR.
CONCLUSION
The conscious rabbit model for PD can be used for repeated studies on peritoneal transport. | pubmed_546_12988 |
pubmed_744_14132 | Reactive oxygen species (ROS), generated by endogenous and exogenous sources, cause significant damage to macromolecules, including DNA. To determine the cellular effects of induced, oxidative DNA damage, we established a relationship between specific oxidative DNA damage levels and biological consequences produced by acute H2O2 exposures in yeast strains defective in one or two DNA damage-handling pathways. We observed that unrepaired, spontaneous DNA damage interferes with the normal cellular response to exogenous oxidative stress. In addition, when base excision repair (BER) is compromised, there is a preference for using recombination (REC) over translesion synthesis (TLS) for handling H2O2-induced DNA damage. The global genome transcriptional response of these strains to exogenous H2O2 exposure allowed for the identification of genes responding specifically to induced, oxidative DNA damage. We also found that the presence of DNA damage alone was sufficient to cause an increase in intracellular ROS levels. These results, linking DNA damage and intracellular ROS production, may provide insight into the role of DNA damage in tumor progression and aging. To our knowledge, this is the first report establishing a relationship between H2O2-induced biological endpoints and specific oxidative DNA damage levels present in the genome. | 10.1093/nar/gkh696 |
pubmed_17_11577 | BACKGROUND
In combination with other traditional Chinese medicines, Breynia officinalis, a species of Euphorbiaceae, has long been used to treat contusions, heart failure, venereal diseases, growth retardation, and conjunctivitis. B. officinalis, regarded as a poison, was mistaken for a similar plant, Securinega suffruticosa, and cooked in a soup used for the treatment of muscle soreness, lumbago, and as a tonic in this outbreak.
CASE SERIES
Nineteen patients, 11 males and 8 females (average age 49.2 +/- 9.1 years) consumed an average of 130 mL (30-900 mL) of soup containing B. officinalis stems. Fourteen patients developed diarrhea, 10 experienced nausea and chilly sensations, 9 had sensations of abdominal fullness, and 7 suffered from vomiting. The results of liver function tests (LFTs) indicated that the observed maximum median level of alanine aminotransferase (ALT) was 647U/L (range 89-9440 U/L), aspartate aminotransferase (AST) 314 U/L (range 47-7756 U/L), alkaline phosphatase 251 U/L (range 224-278 U/L), and gamma glutamyl transpeptidase 106 U/L (range 84-313 U/L). The median time to the observed median peak levels was 3 days for ALT, 2 days for AST, 5 days for alkaline phosphatase, and 12 days for gamma glutamyl transpeptidase. With supportive treatment, the majority of abnormalities in 14 of the cases resolved within 6 months of exposure.
CONCLUSIONS
The consumption of a soup containing B. officinalis Hemsley resulted in dose-related toxic effects. Clinical toxicity consisted primarily of gastrointestinal symptoms and signs and hepatotoxicity. Hepatocellular liver injury rather than cholestatic liver injury was observed. Marked jaundice did not develop. | 10.1081/clt-120023760 |
pubmed_1044_24415 | Pain, including chronic non-cancer pain (CNCP), is a common reason for primary care consultation. CNCP encompasses a heterogeneous group of patients, whose care is often complex. The increase in opioid prescription in Switzerland and worldwide is associated with CNCP, while opioid use for this indication is debated. Several studies suggest a limited effect on pain and function, while adverse effects are frequent. This article aims to summarize what is known about opioid prescription for CNCP and international guidelines and highlight important aspects for the general practitioner. | 10.53738/REVMED.2022.18.787.1238 |
pubmed_299_2372 | This is the first report of comparative metagenomic analyses of BIOLAK sludge and anaerobic/anoxic/oxic (A2O) sludge. In the BIOLAK and A2O sludge metagenomes, 47 and 51 phyla were identified respectively, more than the numbers of phyla identified in Australia EBPR (enhanced biological phosphorus removal), USA EBPR and Bibby sludge. All phyla found in the BIOLAK sludge were detected in the A2O sludge, but four phyla were exclusively found in the A20 sludge. The proportion of the phylum Ignavibacteriae in the A2O sludge was 2.0440%, which was 3.2 times as much as that in the BIOLAK sludge (0.6376%). Meanwhile, the proportion of the bacterial phylum Gemmatimonadetes in the BIOLAK sludge was 2.4673%, which was >17 times as much as that in the A2O sludge (0.1404%). The proportion of the bacterial phylum Chlamydiae in the BIOLAK metagenome (0.2192%) was >6 times higher than that in the A2O (0.0360%). Furthermore, 167 genera found in the A20 sludge were not detected in the BIOLAK sludge. And 50 genera found in the BIOLAK sludge were not detected in the A20 sludge. From the analyses of both the phylum and genus levels, there were huge differences between the two biological communities of A2O and BIOLAK sludge. However, the proportions of each group of functional genes associated with metabolism of nitrogen, phosphor, sulfur and aromatic compounds in BIOLAK were very similar to those in A2O sludge. Moreover, the rankings of all six KEGG (Kyoto Encyclopedia for Genes and Genomes) categories were identical in the two sludges. In addition, the analyses of functional classification and pathway related nitrogen metabolism showed that the abundant enzymes had identical ranking in the BIOLAK and A2O metagenomes. Therefore, comparative metagenomics of BIOLAK and A2O activated sludge indicated similar function assignments from the two different biological communities. | pubmed_299_2372 |
pubmed_57_7830 | BACKGROUND
Current methods for testing treatments for veterinary surgical site infections can successfully emulate elements of a chronic wound, but these are time consuming and costly, requiring specialized laboratory equipment and considerable space to house study animals. Microfluidic devices however, can be coated with collagen and maintained at basal body temperature, providing a more cost-effective and space-saving model of a chronic wound. Our study assesses the applicability of a new microfluidic model by testing the activity of DispersinB against biofilms of methicillin-resistant Staphylococcus pseudintermedius (MRSP); DispersinB has been shown to prevent biofilm growth of Staphylococcus epidermidis, another prominent wound colonizer.
RESULTS
We successfully developed a microfluidic model to examine the effects of antimicrobial therapy on biofilms formed by organisms associated with wound infections in companion animals (e.g. MRSP). Although, we were unable to recapitulate previous findings that DispersinB-Gentamycin is highly effective against Staphylococcal biofilms using this model, we were able to confirm its effect in a microtitre plate. Differences in the experimental conditions likely account for this result (e.g. strains tested, flow conditions, treatment time, etc.). In the microtitre plate assay, DispersinB inhibited biofilm growth after a 24 hour period; there was an inverse relationship between the concentration of DispersinB-Gentamycin and the amount of biofilm remaining following treatment. Collagen-coated microtitre plates showed a similar result, but this did not correlate as well; collagen, the most abundant protein in the body may help to retain the biomass of treated biofilms.
CONCLUSIONS
Our model may be useful in examining the effect of treatment on wound infections, although we acknowledge that in this model the test organisms may be more recalcitrant to antimicrobials than in other published systems. We contend that this may in fact better represent the conditions in vivo, where organisms associated with chronic wound infections are highly resistant to antimicrobials. | 10.1186/1477-3155-12-1 |
pubmed_468_8554 | The article deals with the technique of economic analysis of effectiveness of functioning of multi-profile curative preventive medical institution in the conditions of transition to the payment according the completed case of treatment. The necessity of the measures targeted to prevent the financial losses under the new form of payment for hospital care is proved. | pubmed_468_8554 |
pubmed_559_7472 | BACKGROUND
Cardiac dysfunction can prevent successful discontinuation of mechanical ventilation. Critically ill patients may have undetected cardiac disease, and cardiac dysfunction can be produced or exacerbated by underlying pathophysiology.
OBJECTIVE
To describe and compare hemodynamic function and cardiac rhythm during baseline mechanical ventilation with function and rhythm during a trial of continuous positive airway pressure in medical intensive care patients.
METHODS
A convenience sample of 43 patients (53% men; mean age 51.1 years) who required mechanical ventilation were recruited for this pilot study. Cardiac output, stroke volume, arterial blood pressure, heart rate, cardiac rhythm, and plasma catecholamine levels were measured during mechanical ventilation and during a trial of continuous positive airway pressure.
RESULTS
One third of the patients had difficulty discontinuing mechanical ventilation. Successful patients had significantly increased cardiac output and stroke volume without changes in heart rate or arterial pressure during the trial of continuous positive airway pressure. Unsuccessful patients had no significant changes in cardiac output, stroke volume, or heart rate but had a significant increase in mean arterial pressure. The 2 groups of patients also had different patterns in ectopy. Concurrently, catecholamine concentrations decreased in the successful patients and significantly increased in the unsuccessful patients during the trial.
CONCLUSIONS
Patterns of cardiac function and plasma catecholamine levels differed between patients who did or did not achieve spontaneous ventilation with a trial of continuous positive airway pressure. Cardiac function must be systematically considered before and during the return to spontaneous ventilation to optimize the likelihood of success. | pubmed_559_7472 |
pubmed_446_19171 | The limited amount of available epithelial tissue is considered a main cause of the high rate of urethral reconstruction failures. The aim of this study was to investigate whether epithelial-differentiated rabbit adipose-derived stem cells (Epith-rASCs) could play a role of epithelium in vivo functionally and be a potential substitute of urothelium. Substitution urethroplasty was performed to repair an anterior urethral defect in male New Zealand rabbits using Epith-rASCs seeded bladder acellular matrix grafts (BAMGs) after 5-bromo-2'-deoxyuridine (BrdU) labeling, based on the in vitro epithelial induction system we previously described. Urethroplasty with cell-free BAMGs and with undifferentiated rASCs (Und-rASCs) seeded BAMGs were performed as controls. After surgery, a notable amelioration of graft contracture and recovery of urethral continuity were observed in the Epith-rASCs/BAMG group by retrograde urethrograms and macroscopic inspection. Immunofluorescence revealed that the BrdU-labeled Epith-rASCs/Und-rASCs colocalized with cytokeratin 13 or myosin. Consistent with the results of western blotting, at early postimplantation stage, the continuous epithelial layer with local multilayered structure was observed in the Epith-rASCs/BAMG group, whereas no significant growth and local monolayer growth profile of epithelial cells were observed in the BAMG and Und-rASCs/BAMG group, respectively. The results showed that Epith-rASCs could serve as a potential substitute of urothelium for urethral tissue engineering and be available to prevent lumen contracture and subsequent complications including recurrent stricture. | 10.1089/ten.TEA.2013.0122 |
pubmed_100_15955 | Embryonic stem cells (ESCs) generated from the in-vitro culture of blastocyst stage embryos are known as equivalent to blastocyst inner cell mass (ICM) in-vivo. Though several reports have shown the expression of germ cell/pre-meiotic (GC/PrM) markers in ESCs, their functional relevance for the pluripotency and germ line commitment are largely unknown. In the present study, we used mouse as a model system and systematically analyzed the RNA and protein expression of GC/PrM markers in ESCs and found them to be comparable to the expression of cultured pluripotent cells originated from the germ line. Further, siRNA knockdown experiments have demonstrated the parallel maintenance and independence of pluripotent and GC/PrM networks in ESCs. Through chromatin immunoprecipitation experiments, we observed that pluripotent cells exhibit active chromatin states at GC marker genes and a bivalent chromatin structure at PrM marker genes. Moreover, gene expression analysis during the time course of iPS cells generation revealed that the expression of GC markers precedes pluripotency markers. Collectively, through our observations we hypothesize that the chromatin state and the expression of GC/PrM markers might indicate molecular parallels between in-vivo germ cell specification and pluripotent stem cell generation. | 10.1371/journal.pone.0022413 |
pubmed_664_4812 | The interaction between resist and template during the separation process after nanoimprint lithography (NIL) can cause the formation of defects and damage to the templates and resist patterns. To alleviate these problems, fluorinated self-assembled monolayers (F-SAMs, i.e. tridecafluoro-1,1,2,2,tetrahydrooctyl trichlorosilane or FDTS) have been employed as template release coatings. However, we find that the FDTS coating undergoes irreversible degradation after only 10 cycles of UV nanoimprint processes with SU-8 resist. The degradation includes a 28% reduction in surface F atoms and significant increases in the surface roughness. In this paper, diamond-like carbon (DLC) films were investigated as an alternative material not only for coating but also for direct fabrication of nanoimprint templates. DLC films deposited on quartz templates in a plasma enhanced chemical vapor deposition system are shown to have better chemical and physical stability than FDTS. After the same 10 cycles of UV nanoimprints, the surface composition as well as the roughness of DLC films were found to be unchanged. The adhesion energy between the DLC surface and SU-8 is found to be smaller than that of FDTS despite the slightly higher total surface energy of DLC. DLC templates with 40 nm features were fabricated using e-beam lithography followed by Cr lift-off and reactive ion etching. UV nanoimprinting using the directly patterned DLC templates in SU-8 resist demonstrates good pattern transfer fidelity and easy template-resist separation. These results indicate that DLC is a promising material for fabricating durable templates for UV nanoimprint lithography. | 10.1088/0957-4484/19/10/105302 |
pubmed_933_25180 | 1. The quantitative, absolute method of agglutinin estimation is extended to the reaction between Types I and II pneumococcus R (S) suspensions prepared in various ways and antisera from rabbits injected with these cells. 2. Quantitative estimations of the amount of antibody to pneumococcus C substance are also given. 3. The significance of the data is discussed. | 10.1084/jem.67.4.545 |
pubmed_570_24489 | Neisseria gonorrhoeae can engage human complement receptor 3 (CR3) directly or through surface-bound iC3b. Factor H (fH) that binds to bacteria facilitates conversion of C3b to iC3b. fH also binds directly to CR3 on professional phagocytes. Certain nonprofessional phagocytes, such as primary cervical epithelial cells, also express CR3. We hypothesized that fH could bridge bacteria to CR3 and facilitate gonococcal association with host cells. Specificity of the fH-CR3 interaction was confirmed using human CR3-transfected Chinese hamster ovary (CHO-CR3) cells. Using recombinant proteins that comprised contiguous fH domains (fH contains 20 short consensus repeat [SCR] domains) fused to murine Fc, we observed strong binding through SCRs 18-20, whereas weaker binding occurred through SCRs 6-10. Both regions also bound to unsialylated porin (Por) B.1A-expressing N. gonorrhoeae. Accordingly, fH-related protein 1 (three of its five SCRs are highly homologous to fH SCRs 18-20) bound to CHO-CR3 and to unsialylated PorB.1A gonococci. An alternatively spliced variant of fH called fH-like protein-1 (contains fH SCRs 1-7) bound to gonococci but minimally to CHO-CR3. An fH SCRs 6-20 construct enhanced binding of unsialylated PorB.1A gonococci to CHO-CR3. However, a construct that contained only the apparently relevant SCRs (6, 7, and 18-20) bound to CHO-CR3 and to gonococci separately, but did not enhance bacteria-CR3 interactions, suggesting that the intervening SCRs (8-17) may impart a configurational and spatial requirement for fH to bridge gonococci to CR3. These results indicate adherence between fH-coated gonococci and CR3 and may provide a means for gonococci to gain sanctuary into nonprofessional phagocytes. | 10.4049/jimmunol.0904191 |
pubmed_20_4738 | Social cues presented at visual fixation have been shown to strongly influence an observer's attention and response selection. Here we ask whether the same holds for cues (initially) presented away from fixation, as cues are commonly perceived in natural vision. In six experiments, we show that extrafoveally presented cues with a distinct outline, such as pointing hands, rotated heads, and arrow cues result in strong cueing of responses (either to the cue itself, or a cued object). In contrast, cues without a clear outline, such as gazing eyes and direction words exert much weaker effects on participants' responses to a target cue. We also show that distraction effects on response times are relatively weak, but that strong interference effects can be obtained by measuring mouse trajectories. Eye tracking suggests that gaze cues are slower to respond to because their direction cannot easily be perceived in extrafoveal vision. Together, these data suggest that the strength of an extrafoveal cue is determined by the shape of the cue outline, rather than its biological relevance (i.e., whether the cue is provided by another human being), and that this shape effect is due to how easily the direction of a cue can be perceived in extrafoveal vision. | 10.1007/s00426-015-0733-2 |
pubmed_902_12321 | In order to promote wound repair and induce tissue regeneration, an engineered hyaluronan (HA) hydrogel - Carbylan GSX, which contains di(thiopropionyl) bishydrazide-modified hyaluronic acid, di(thiopropionyl) bishydrazide-modified gelatin and polyethylene glycol diacrylate - has been developed for extracellular matrix (ECM) defects of the superficial and middle layers of the lamina propria. The purpose of this study was to evaluate the biocompatibility of Carbylan GSX in a previously established immortalized human vocal fold fibroblast (hVFF) cell line prior to human clinical trials. Immortalized hVFF proliferation, viability, apoptosis and transcript analysis for both ECM constituents and inflammatory markers were measured for two-dimensional and three-dimensional (3-D) culture conditions. There were no significant differences in morphology, cell marker protein expression, proliferation, viability and apoptosis of hVFF cultured with Carbylan GSX compared to Matrigel, a commercial 3-D control, after 1 week. Gene expression levels for fibromodulin, transforming growth factor-beta1 and tumor necrosis factor-alpha were similar between Carbylan GSX and Matrigel. Fibronectin, hyaluronidase 1 and cyclooxygenase II expression levels were induced by Carbylan GSX, whereas interleukins 6 and 8, Col I and hyaluronic acid synthase 3 expression levels were decreased by Carbylan GSX. This investigation demonstrates that Carbylan GSX may serve as a natural biomaterial for tissue-engineering of human vocal folds. | 10.1016/j.actbio.2010.01.032 |
pubmed_983_7280 | The combination of ZnEt(2) and chiral pyridinebisoxazoline (pybox) or pyridinebisimidazoline (pybim) ligands catalyzed the asymmetric hydrosilylation of aryl, alkyl, cyclic, heterocyclic, and aliphatic ketones. Under mild conditions, high yields and good enantioselectivities were achieved. ESI measurements allowed for the characterization of the active catalyst. | 10.1002/asia.201100561 |
pubmed_222_1143 | Conventional 4-field box radiotherapy technique induces high morbidity for patients with localized prostatic cancer. Using a patient daily diary, the present study compared side-effects after conventional radiotherapy with conformal radiotherapy for prostate cancer. Fifty-eight patients treated with the conventional technique (with or without sucralfate) were compared with 72 patients treated with conformal technique. The patient groups were compared with an age-matched control population. Patients treated with conformal technique were also evaluated regarding acute and late urinary problems. Results showed that patients treated with conformal technique reported significantly fewer side-effects as compared with conventional technique. Patients treated with sucralfate also showed slightly decreased intestinal morbidity in comparison to non-sucralfate group. Acute and late morbidity evaluated by the patients was decreased after conformal radiotherapy as compared with the conventional technique. Sucralfate may be of value if conformal radiotherapy is used for dose escalation in prostatic cancer patients. | 10.3109/02841869709001306 |
pubmed_716_9683 | Rhizosphere-associated microbes have important implications for plant health, but knowledge of the association between the pathological conditions of soil-borne virus-infected wheat and soil microbial communities, especially changes in fungal communities, remains limited. We investigated the succession of fungal communities from bulk soil to wheat rhizosphere soil in both infected and healthy plants using amplicon sequencing methods, and assessed their potential role in plant health. The results showed that the diversity of fungi in wheat rhizosphere and bulk soils significantly differed post wheat yellow mosaic virus disease onset. The structure differences in fungal community at the two wheat health states or two compartment niches were evident, soil physicochemical properties (i.e., NH4 +) contribute to differences in fungal community structure and alpha diversity. Comparison analysis showed Mortierellomycetes and Dothideomycetes as dominant communities in healthy wheat soils at class level. The genus Pyronemataceae and Solicoccozyma were significantly are significantly enriched in rhizosphere soil of diseased plant, the genus Cystofilobasidium, Cladosporium, Mortierella, and Stephanonectria are significantly enriched in bulk soil of healthy plant. Co-occurrence network analysis showed that the fungi in healthy wheat soil has higher mutual benefit and connectivity compared with diseased wheat. The results of this study demonstrated that the occurrence of wheat yellow mosaic virus diseases altered both fungal community diversity and composition, and that NH4 + is the most important soil physicochemical factor influencing fungal diversity and community composition. | 10.3389/fbioe.2022.1033991 |
pubmed_670_8277 | Parvalbumin (a calcium-binding protein)-immunoreactive (PV-Ir) neurons in the cerebral cortex were examined in 20 postmortem brains obtained from elderly controls and patients with Pick's disease (PD). The type of PV-Ir neurons and their distribution in control and PD brains were similar. The number of PV-Ir neurons in PD brains did not differ significantly from that in the control brains either. These findings suggested that PV-Ir neurons in the cortex are not affected in PD brains. A significant loss of PV-Ir neurons has already been reported in brains obtained from patients with Alzheimer-type dementia (ATD), and the present results suggest the possibility that the damage of PV-Ir neurons might be comparatively selective for ATD brains. | 10.1007/BF00314780 |
pubmed_754_7603 | Plasmid YEp ( ADE1 )1a, containing a 2.7-kb Sau3A fragment of Saccharomyces cerevisiae DNA inserted at the BamHI site of the yeast shuttle vector pBTI -1 (Morris et al., 1981), results in high frequency, unstable transformation of ade 1 yeast strains. A second plasmid, YRp ( ADE1 )2, containing adjacent 0.5-kb and 3.0-kb BamHI fragments in pBR322 gave three types of yeast transformants: (1) transformants carrying extrachromosomal copies of the plasmid which indicate the presence of a functional ars sequence, (2) transformants indistinguishable from ade 1 strains by hybridization analysis, and (3) a transformant carrying a multimeric form of YRp ( ADE1 )2. Cells transformed with either of the plasmids are free of the red pigment characteristic of ade 1 mutants and indicate potential for direct colour-based selection of yeast transformants using ADE1 plasmids. | 10.1016/0378-1119(84)90144-6 |
pubmed_236_13384 | In a network of excitatory and inhibitory neurons, hyperpolarization-activated inward currents can help to produce population rhythms in which individual cells participate sparsely and randomly. A shift in the activation curve of such a current changes the fraction of the cells participating in any given cycle of the population rhythm, thus changing the amplitude of the field potential. Furthermore, the frequency of the population rhythm remains relatively fixed over a substantial range of amplitudes, allowing the population rhythm to play a separate processing role from that of the individual components. | 10.1073/pnas.91.22.10586 |
pubmed_382_6622 | Pseudomonas sp. DJ-12 degrades 4-chlorobenzoate through hydrolytic dechlorination to produce 4-hydroxybenzoate and a chloride ion. The fcbB gene encoding the 4-chlorobenzoate-coenzyme A (4CBA-CoA) dehalogenase which catalyzes the nucleophilic substitution reaction to convert 4CBA-CoA to 4-hydroxybenzoate-coenzyme A (4HBA-CoA) in the consecutive steps of dechlorination was cloned from the chromosome of the organism. A nucleotide sequence analysis of the gene showed an open reading frame consisting of 810 nucleotides, which can encode for a polypeptide of molecular mass 30 kDa, containing 269 amino acid residues. A promoter-like sequence (-35 and -10 region) and a putative ribosome-binding sequence were identified. A deduced amino acid sequence of the 4CBA-CoA dehalogenase showed 86%, 50%, and 50% identity with those of corresponding enzymes in the Pseudomonas sp. CBS3, Arthrobacter sp. SU, and Arthrobacter sp. TM1, respectively. | pubmed_382_6622 |
pubmed_500_11415 | To assess the role of total gastrectomy in the treatment of advanced gastric cancer, we reviewed the records of 27 patients who underwent the procedure from 1979 to 1988. Operative mortality was 4 percent (1 of 27), and postoperative morbidity occurred in 48 percent of the patients. Twenty-five of 26 patients were tolerating solid food at the time of discharge; 21 were able to maintain oral alimentation until just prior to their death. Median survival following the operation was 15 months (range: 2 to 110 months), with a 62 percent absolute 1-year survival rate and a 38 percent 2-year survival rate. On the basis of these results, we conclude that in patients with advanced gastric carcinoma, total gastrectomy with Roux-Y esophagojejunostomy can be performed with an acceptable morbidity and mortality, provides significant palliation by restoring the patient's ability to eat, and should be performed when technically feasible, even in the presence of gross residual disease. | 10.1016/0002-9610(89)90203-1 |
pubmed_43_5504 | OBJECTIVES
To critically evaluate the cost-effectiveness of the Midwifery Initiated Oral Health-Dental Service (MIOH-DS) designed to improve oral health of pregnant Australian women. Previous efficacy and process evaluations of MIOH-DS showed positive outcomes and improvements across various measures.
DESIGN AND SETTING
The evaluation used a cost-utility model based on the initial study design of the MIOH-DS trial in Sydney, Australia from the perspective of public healthcare provider for a duration of 3 months to 4 years.
PARTICIPANTS
Data were sourced from pregnant women (n=638), midwives (n=17) and dentists (n=3) involved in the MIOH trial and long-term follow-up.
COST MEASURES
Data included in analysis were the cost of the time required by midwives and dentists to deliver the intervention and the cost of dental treatment provided. Costs were measured using data on utilisation and unit price of intervention components and obtained from a micro-costing approach.
OUTCOME MEASURES
Utility was measured as the number of Disability Adjusted Life Years (DALYs) from health-benefit components of the intervention. Three cost-effectiveness analyses were undertaken using different comparators, thresholds and time scenarios.
RESULTS
Compared with current practice, midwives only intervention meets the Australian threshold (A$50 000) of being cost-effective. The midwives and accessible/affordable dentists joint intervention was only 'cost-effective' in 6 months or beyond scenarios. When the midwife only intervention is the comparator, the midwife/dentist programme was 'cost-effective' in all scenarios except at 3 months scenario.
CONCLUSIONS
The midwives' only intervention providing oral health education, assessment and referral to existing dental services was cost-effective, and represents a low cost intervention. Midwives' and dentists' combined interventions were cost-effective when the benefits were considered over longer periods. The findings highlight short and long term economic benefits of the programme and support the need for policymakers to consider adding an oral health component into antenatal care Australia wide.
TRIAL REGISTRATION NUMBER
ACTRN12612001271897; Post-results. | 10.1136/bmjopen-2020-047072 |
pubmed_724_22863 | Interindividual variability in pain perception and response to opioids in terms of efficacy and side effects has been long noted. Numerous genes have been proposed as ideal candidate genes for the study of the genetic component of pain and pharmacogenetics of opioids. Despite the inherent complexity in studying pain, it is obvious that several genetic polymorphisms contribute to modulate nociception and the antinociceptive effects of opioids; specifically those involved in pharmacokinetics and the metabolism of opioids (cytochrome P450) and neurotransmitters (catechol-O-methyltransferase), as well as those affecting pharmacodynamics or the drug targets such as the mu-opioid receptor or the unexpected melanocortin 1-receptor. | 10.1016/j.lpm.2007.07.041 |
pubmed_69_10928 | Cells are constantly challenged by DNA damage and protect their genome integrity by activation of an evolutionary conserved DNA damage response pathway (DDR). A central core of DDR is composed of a spatiotemporally ordered net of post-translational modifications, among which protein phosphorylation plays a major role. Activation of checkpoint kinases ATM/ATR and Chk1/2 leads to a temporal arrest in cell cycle progression (checkpoint) and allows time for DNA repair. Following DNA repair, cells re-enter the cell cycle by checkpoint recovery. Wip1 phosphatase (also called PPM1D) dephosphorylates multiple proteins involved in DDR and is essential for timely termination of the DDR. Here we have investigated how Wip1 is regulated in the context of the cell cycle. We found that Wip1 activity is downregulated by several mechanisms during mitosis. Wip1 protein abundance increases from G(1) phase to G(2) and declines in mitosis. Decreased abundance of Wip1 during mitosis is caused by proteasomal degradation. In addition, Wip1 is phosphorylated at multiple residues during mitosis, and this leads to inhibition of its enzymatic activity. Importantly, ectopic expression of Wip1 reduced γH2AX staining in mitotic cells and decreased the number of 53BP1 nuclear bodies in G(1) cells. We propose that the combined decrease and inhibition of Wip1 in mitosis decreases the threshold necessary for DDR activation and enables cells to react adequately even to modest levels of DNA damage encountered during unperturbed mitotic progression. | 10.4161/cc.23057 |
pubmed_65_529 | The authors studied life expectancy and risk factors for mortality of persons in the vegetative state (VS). The study participants were 1,021 California patients in the VS during 1981-1996. Because of the large sample size, the authors were able to use multivariate methods to assess the effect of several risk factors on mortality. The authors found a strong secular trend in infant mortality, with rates in the mid-1990s being only one third of those in the early 1980s (P < 0.01). A smaller secular trend was observed for children aged 2-10 years and none for older patients. The mortality risk for older patients fell by approximately 8% for each year since the onset of the VS. The need for gastrostomy feeding was associated with a substantially higher risk, especially for infants and older patients (P < 0.01). Ventilator dependence also appeared to be a risk factor. On the basis of recent mortality rates, life expectancy in the VS is frequently higher than has generally been thought. For example, it is 10.5 additional years (+/- 2 years) for a 15-year-old patient who has been in the VS for 1 year, and 12.2 years for a 15-year-old patient who has been in the VS for 4 years. | 10.1016/s0887-8994(99)00051-x |
pubmed_55_17815 | The preparation, characterization, and optimization of the functional properties of mono- and polynuclear coordination complexes containing heteroaromatic nitrogen ligands are discussed here, taking the advantage of numerous studies performed in our laboratories on exploring a variety of different metal ions and polytopic ligands. We highlight how very minor changes in connectivity, composition, and polarity of the molecular entities employed in the self-assembly steps may significantly affect the structural, thermal, sorptive, magnetic, and mesomorphic behavior of the resulting materials. Examples from three different classes are included: 1) pyrazolate-based polynuclear coordination compounds, 2) homoleptic and heteroleptic coordination polymers, and 3) 2,2'-bipyridine metal-based liquid crystals. | 10.1002/chem.200901923 |
pubmed_639_10298 | The development of materials integrated with ultrasmall multi-metal nanoparticles (UMMNs) and mesoporous zeolite is a considerable challenge in chemistry and materials science. We designed a trifunctional surfactant, in which the pyridyl benzimidazole in the hydrophobic tail generates the mesopores through π-π stacking; the diquaternary ammonium in the hydrophilic headgroup direct the formation of MFI zeolite sheets and the nitrogen atoms in the heterocyclic rings coordinate with various metal ions to form UMMNs confined in the zeolite matrix after calcination and reduction. A library of 56 UMMNs confined within both micropores and mesopores of MFI zeolites (MMZs) with 4 mono-, 14 bi- and 38 tri-metallic nanoparticles (sizes of 1.3-4.7 nm) of combinations of Rh, Pd, Pt, Au, Fe, Co, Ni, Cu and Zn were made. An improved catalytic performance was exhibited in the sequence of Rh-MMZ<Rh/Pt-MMZ<Rh/Pt/Ni-MMZ for the mild oxidation of methane to methanol or liquid acid. | 10.1002/anie.202103007 |
pubmed_631_14528 | PURPOSE
To evaluate whether carbonic anhydrase inhibitors reduce the macular thickness and/or cystic spaces in patients with macular telangiectasia (MacTel) Type 2.
METHODS
Retrospective review of patients with nonproliferative cystoid changes associated with MacTel seen at the University of Iowa between 2009 and 2012. Carbonic anhydrase inhibitors were used in 8 patients with MacTel Type 2. Five patients with MacTel Type 2 were observed during this period. Initial and final visual acuities were documented. The presence of cystic spaces and the retinal thickness were measured with spectral-domain optical coherence tomography.
RESULTS
Patients treated with oral carbonic anhydrase inhibitors showed significant reduction in both the cystoid cavities and central macular thickness when compared with the patients who were observed (-12.2 μm; P = 0.020). The reduction in retinal thickness was more pronounced in patients receiving acetazolamide (-20.13 μm; P = 0.007) compared with methazolamide (-6.25 μm; P = 0.177). There was no significant change in visual acuity in patients receiving carbonic anhydrase inhibitors. Five patients with MacTel Type 2 did not receive treatment and demonstrated no change in visual acuity, cystoid cavities, or central macular thickness.
CONCLUSION
Oral carbonic anhydrase inhibitors, particularly acetazolamide, may decrease macular cystic cavities and reduce central macular thickness but does not appear to improve visual acuity. These findings have yet to be confirmed with a prospective treatment trial. | 10.1097/IAE.0000000000000093 |
pubmed_154_20430 | STATEMENT OF PROBLEM
Indirect composite or ceramic fixed partial dentures (FPDs) have become an alternative to conventional metal-ceramic adhesive fixed partial dentures (AFPDs). Little information about the adequate restorative material and tooth preparation design for inlay-anchored AFPDs is available to the clinician.
PURPOSE
The purposes of this simulation study were: (1) to use 2-dimensional finite element modeling to simulate stresses at the surface and interface of 3-unit posterior AFPDs made with 6 different restorative materials, and (2) to investigate the influence of 3 different abutment preparation configurations on the stress distribution within the tooth/restoration complex.
MATERIAL AND METHODS
A mesio-distal cross-section of a 3-unit AFPD was digitized and used to create 2-dimensional models of the periodontal membrane, supporting bone, different restorative materials (gold, alumina, zirconia, glass-ceramic, composite, and fiber-reinforced composite), and different abutment preparation configurations (interproximal slots vs. 2-surface [MO, DO] vs. 3-surface [MOD]). A simulated 50-N vertical occlusal load was applied to the standardized pontic element. The principal stress within the restorative materials, stresses at the tooth/restoration interface, and surface tangential stresses at the level of the pontic were calculated in MPa from the postprocessing files and compared to each other.
RESULTS
All materials and tooth preparation design exhibited a similar stress pattern, with a definite compressive area at the occlusal side of the pontic, a tensile zone at the gingival portion of the pontic, and tensile stress peaks in the abutment/pontic connection areas. Among isotropic materials, standard non-reinforced composites exhibited better stress transfer and reduced tensile stresses at the adhesive interface than ceramics and gold. Optimized placement of the glass fibers within the composite resulted in similar stress distribution when tested in 2-surface abutment preparation configuration. There was no detectable influence of preparation design on the behavior of the pontic area. Among all 3 preparation designs, only the DO design exhibited almost pure compression at the interface.
CONCLUSION
Within the limitations of this simulation experiment, the composite materials tested demonstrated a resilient component that favored stress transfer within the tooth/restoration complex. Their clinical use, however, may be contraindicated due to insufficient strength and fracture toughness. The addition of extremely tough fibers to composites represents the most promising combination. Clinical trials are required to ensure that veneering composite can survive under clinical conditions. | 10.1067/mpr.2002.124367 |
pubmed_618_24519 | Cortical thickness (CT) is an important morphometric measure that has implications for psychiatric and neurologic processes. We propose a novel approach for automatically computing CT in an accurate and robust manner using LOGISMOS-B: Layered Optimal Graph Image Segmentation of Multiple Objects and Surfaces for the Brain. LOGISMOS-B is a cortical surface segmentation method based on LOGISMOS graph segmentation and generalized gradient vector flows. We evaluate our method on two different datasets (n = 83 total). The results show that LOGISMOS-B is more accurate than the popular FreeSurfer (FS) method and provides more reliable thickness measurements across a variety of challenging images. LOGISMOS-B accurately recovers known CT patterns, both across cortical lobes and locally, such as between the banks of the central sulcus, in healthy subjects and MS patients. Manual landmarks indicate a signed surface distance of 0.081 +/- 0.447mm for WM and 0.018 +/- 0.498mm for LOGISMOS-B, compared to 0.263 +/- 0.452mm for WM and -0.167 +/- 0.556mm for GM for FS, highlighting the surface placement accuracy of LOGISMOS-B. Finally, a regresion study shows that LOGISMOS-B provides strong correlation with age and plausible annual thinning rates across the cortex, with locally discerning thinning patterns, in agreement with the literature. | 10.1007/978-3-319-10404-1_90 |
pubmed_93_10793 | Antigen-independent B-cell development occurs in several stages that depend on the expression of Ig heavy and light chain. We identified a line of mice that lacked mature B cells in the spleen. This mouse line carried approximately 11 copies of a transgene of the murine heavy chain constant region locus, and B-lineage cells expressed excessive amounts of the intracellular μ heavy chain. B-cell development failed in the bone marrow at the pro/pre B-cell transition, and examination of other lines with various copy numbers of the same transgene suggested that deficiencies in B-cell development increased with increased transgene copy number. Expression of a transgenic (Tg) light chain along with the Tg μ heavy chain led to minimal rescue of B-cell development in the bone marrow and B cells in the spleen. There are several potential mechanisms for the death of pro/pre B cells as a consequence of excess heavy chain expression. | 10.1093/intimm/dxr049 |
pubmed_508_2749 | INTRODUCTION
Seizures are accompanied by autonomic dysfunction which in turn influences cardiovascular variables. A method for simultaneous acquisition of electroencephalogram (EEG) and arterial blood pressure (BP) during seizures in conscious animals has not previously been described.
METHODS
The effect of pentylenetetrazole (PTZ) was first studied on isolated rat atria. EEG and BP were then monitored simultaneously in conscious rats, with a chronically implanted radiotelemetric device. Changes in systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP) and heart rate (HR) during epileptiform seizures induced by intraperitoneal administration of PTZ were monitored to validate the method.
RESULTS
PTZ did not have significant inotropic or chronotropic effect in isolated atria. The radiotelemetry system used to acquire data in unrestrained conscious rats enabled us to study neurological excitation (EEG) and cardiovascular variables (BP and HR) during seizures. Our results demonstrated that this method can be used to study the effect of neuronal excitation on cardiovascular variables and vice versa. | 10.1016/j.vascn.2006.12.006 |
pubmed_1107_10168 | HIV-1 aspartic protease (PR) is a promising target for acquired immunodeficiency syndrome (AIDS) therapy, and the development of PR inhibitors can be accelerated by computer-aided design methods. We describe an approach for the design of new inhibitors, based on the modification of a known reference inhibitor, and the calculation of relative binding energies, taking into account contributions from all species in the binding equilibrium (inhibitor, PR and inhibitor/PR complex), as well as their solvation. This allows for a rational selection of new structures that are likely to have increased inhibition potency. We have analyzed reduced amide bond hexapeptides (Ac-P3-P2-P1-phi[CH2-NH]-P1'-P2-P3'-NH2), based on the structure of the known inhibitor MVT-101. A maximum gain in binding energy (approximately -55 kcal/mol) is observed when Phe or Tyr are present in positions P1 and P1', Glu in position P2' and aromatic residues (Phe, Trp or Tyr) in positions P3 and P3', while, in general, the presence of positively charged residues is destabilizing. This specificity is explained in terms of the interaction of individual inhibitor residues with proximal and distal PR residues. The validity of this computational approach has been confirmed by solid-phase synthesis of several of the designed pseudopeptides, followed by in vitro enzyme inhibition assaying. The best candidate structures show IC50 values in the low nanomolar range. | pubmed_1107_10168 |
pubmed_835_17874 | BACKGROUND
Numerous studies have reported that eveningness is associated with increased alcohol consumption. However, biological markers of circadian timing, such as dim light melatonin onset (DLMO) and circadian photoreceptor responsivity (post-illumination pupil response, PIPR), have rarely been assessed in the context of habitual alcohol consumption. This study aimed to examine sleep, circadian timing, and photoreceptor responsivity in adult alcohol drinkers.
METHODS
Participants (21 to 45 years) included 28 light and 50 heavy drinkers. The 8-day study consisted of a week of ad lib sleep monitored with wrist actigraphy, followed by a 9-h laboratory session with a photoreceptor responsivity and circadian phase assessment.
RESULTS
The heavy drinkers obtained on average 28 more minutes of sleep (p = 0.002) and reported more eveningness than the light drinkers (p = 0.029). There was a trend for a shorter DLMO-midsleep interval (p = 0.059) in the heavy drinkers, reflecting a tendency for them to sleep at an earlier circadian phase. The PIPR in the heavy drinkers was significantly smaller than in the light drinkers (p = 0.032), suggesting reduced circadian photoreceptor responsivity in the heavy drinkers. A larger PIPR was significantly associated with a later DLMO in the light drinkers (r = 0.44, p = 0.019), but this relationship was absent in the heavy drinkers (r = -0.01, p = 0.94).
CONCLUSIONS
These results are consistent with earlier reports of more eveningness and a shorter DLMO-midsleep interval being associated with heavier alcohol drinking. The novel finding of reduced circadian photoreceptor responsivity in heavy drinkers is consistent with prior rodent studies. Future studies should explore the impact of habitual alcohol consumption on other measures of circadian photoreceptor responsivity. | 10.1111/acer.14872 |
pubmed_558_2557 | Lumbocostovertebral syndrome is the association of a congenital lumbar hernia with rib and vertebral anomalies. We report the first case of a laparoscopic repair of a lumbar hernia in a child with lumbocostovertebral syndrome. Laparoscopic lumbar hernia repair appears to be safe and feasible in children. | 10.1089/lap.2008.0278 |
pubmed_940_19859 | We performed 164 laser resections with a neodymiumyttrium-aluminum-garnet (Nd-Yag) laser in 116 patients between January 1992 and December 1997. Seventy-eight patients had malignant neoplasms, 5 had neoplasms of intermediate malignancy and 33 had inflammatory tracheal lesions. Eighteen resections were emergency procedures. All resections were performed with the patient under general anesthesia and preferably breathing spontaneously. Immediate results varied according to the nature and location of the lesion. Treatment was palliative for tumors showing intraluminal proliferation, providing successful reopening of the airway as shown endoscopically in 70% of patients. Mean survival of the 44 patients with malignant lesions who could be followed was 29 weeks, with a median of 15.19 (range, 1-120). The tracheas of patients with inflammatory stenosis were reopened rapidly and emergency tracheostomy was avoided in all cases. One patient with malignant tracheal tumors died during the procedure due to asphyxia related to tracheal hemorrhage. | 10.1016/s0300-2896(15)30368-9 |
pubmed_1020_9553 | The ability to assess balance is essential to determine a patients ability to mitigate any risk of falling. While current assessment tools exist, they either have limitations in that there is no quantitative data recorded, or that they are impractical for general use in clinical settings. In this work, we aim at assessing balance using single-camera videos. In particular, the proposed method uses OpenPose to calculate the Center of Mass and Center of Pressure trajectories. To determine the validity of this approach, estimates obtained in an experimental study were compared to recordings obtained through the use of 3D motion capture and force plate. Our results indicate that this inexpensive, easy to use, and portable alternative has the potential to act as a suitable replacement to assess balance in clinical settings. | 10.1109/EMBC46164.2021.9631001 |
pubmed_184_5059 | A personal series of 93 patients treated by low anterior resection for carcinoma (87) and benign disease (6) is reviewed to highlight the technical problems and complications of the operation. The series comprises two groups for comparison of (i) technique of anstomosis; (ii) the use of protective stoma; and (iii) methods of drainage. | 10.1111/j.1445-2197.1979.tb06437.x |
pubmed_708_15138 | Beef-heart cytochrome c oxidase lacking endogenous lipids can be prepared by cholate-mediated exchange with dimyristoylphosphatidylcholine (Powell, G. L., Knowles, P. F. and Marsh, D. (1985) Biochim. Biophys. Acta 816, 191-194). These preparations retained practically no endogenous cardiolipin (less than 0.19 mol cardiolipin per mol of oxidase) but in Tween 80 they retained unaltered electron transport activity. Resupplementation of the dimyristoylphosphatidylcholine-substituted cytochrome oxidase with cardiolipin and cardiolipin analogues with different numbers of acyl chains or with a methylated headgroup enhanced the activity of the reconstituted enzyme to an extent dependent on the structure of the cardiolipin derivative. The Eadie-Hofstee plot showed biphasic kinetic behavior for all reconstituted preparations, even those completely lacking cardiolipin. This biphasic substrate dependence of the kinetics was simulated using the model of Brzezinski, P. and Malmström, B. G. (Proc. Natl. Acad. Sci. USA 83 (1986) 4282-4286), which implicates two interconverting enzyme conformations in the proton transport step. The activation of cytochrome c oxidase by the cardiolipin analogues could be explained in terms of an electrostatic enhancement of the surface concentrations of both cytochrome c and protons, and a facilitated interconversion between the two enzyme conformations. | 10.1016/0005-2728(90)90090-q |
pubmed_437_19416 | OBJECTIVE
The purpose of our investigation was to determine the frequency of proximate acute and chronic confounding risk factors for acute kidney injury (AKI) in a cohort of adult hospitalized patients with stable renal function who developed AKI following an intravenous (IV) contrast-enhanced computed tomography (CT) examination.
MATERIALS AND METHODS
Institutional review board approval was obtained for this retrospective, Health Insurance Portability and Accountability Act-compliant investigation. Overall, 100 adult inpatients (50 males [mean age = 61 years, range: 24-94 years] and 50 females [mean age = 60 years, range: 20-95 years]) with stable pre-CT renal function who developed post-CT AKI using the Acute Kidney Injury Network (AKIN) laboratory criteria following an IV contrast-enhanced CT examination comprised the study population. Electronic International Classification of Disease-9 analysis followed by a comprehensive manual electronic medical record review was systematically performed by 5 radiologists to identify known acute (n = 24, within 5 days before or 3 days after CT) and chronic (n = 21) risk factors for AKI other than contrast material administration that might confound a diagnosis of contrast-induced nephrotoxicity. Descriptive statistics were performed.
RESULTS
Of 100 inpatients with post-CT AKI, 99 (99%) had 1 or more acute risk factor(s) for AKI other than contrast material administration (median = 3 risk factors, range: 0-8) and 86 (86%) had one or more chronic risk factor(s) for AKI (median = 2 risk factors, range: 0-7). The median number of risk factors (acute or chronic) per patient was 5 (range: 1-13). Only 1 inpatient (1%) developed post-CT AKI without a confounding acute risk factor (estimated glomerular filtration rate = 62-71 mL/min/1.73 m(2), 4 chronic risk factors, and CT 7 days after pancreaticoduodenectomy). The most common acute risk factors were nephrotoxic medications (83%) and parenteral blood product administration (30%). The most common chronic risk factors were hypertension (59%) and chronic kidney disease (56%).
CONCLUSION
Nonconfounded post-CT AKI is rare in hospitalized adults with stable renal function who have been exposed to IV low- or iso-osmolality iodinated contrast material. | pubmed_437_19416 |
pubmed_848_18831 | The effect on renal function (creatinine clearance [Ccreat] and inulin clearance [Cinulin]) of changes in chronic dietary protein intake was studied in seven healthy male subjects. Serial 24-hour urine collections were used to determine creatinine excretion (UcreatV) and Ccreat. Subjects were examined after ad libitum (ad lib) food intake and after 2-week periods of high protein diet ([HPD] 1.6 g/kg body weight [BW] per day) and low protein diet ([LPD] 0.5 g/kg BW per day). Inulin clearance (Cinulin) was determined at the end of each 2-week diet period. UcreatV increased from 1,838.8 +/- 97.2 mumol/kg (20.8 +/- 1.1 mg/kg) BW to 2,068.6 +/- 106.1 mumol/kg (23.4 +/- 1.2 mg/kg) BW daily during HPD and decreased significantly to 1,555.9 +/- 167.9 mumol/kg BW per day (17.6 +/- 1.9 mg/kg BW per day) with beginning of LPD. Ccreat rose from 1.54 +/- 0.09 mL/s 1.73 m2 (92.5 +/- 5.5 mL/s.1.73 m2 (104.7 +/- 4.9 mL/min/1.73 m2) during HPD and decreased to 1.23 +/- 0.04 mL/s.1.73 m2 (74.0 +/- 2.2 mL/min/1.73 m2) with initiation of LPD. There was no difference between Cinulin after HPD (1.42 +/- 0.12 mL/s.1.73 m2; 84.9 +/- 7.2 mL/min/1.73 m2) and after LPD (1.36 +/- 0.05 mL/s.1.73 m2; 81.4 +/- 2.9 mL/min/1.73 m2). This study confirms the effect of protein intake on Ccreat and UcreatV, but fails to show an effect of changes in chronic protein intake on glomerular filtration rate (GFR). Ccreat during dietary protein restriction to 0.5 g/kg/d is similar to Cinulin and may be a useful measure of GFR under circumstances where more specific inulin or isotope studies are not available. | 10.1016/s0272-6386(12)80512-9 |
pubmed_389_481 | OBJECTIVE
To predict first trimester pregnancy outcome using biomarkers in a multicenter cohort.
DESIGN
Case-control study.
SETTING
Three academic centers.
PATIENT(S)
Women with pain and bleeding in early pregnancy.
INTERVENTION(S)
Sera from women who were 5-12 weeks' gestational age with ectopic pregnancy (EP), viable intrauterine pregnancy (IUP), and miscarriage/spontaneous abortion (SAB) was analyzed by ELISA and immunoassay for activin A, inhibin A, P, A Disintegrin And Metalloprotease-12, pregnancy-associated plasma protein A (PAPP-A), pregnancy specific B1-glycoprotein (SP1), placental-like growth factor, vascular endothelial growth factor, glycodelin (Glyc), and hCG. Classification trees were developed to optimize sensitivity/specificity for pregnancy location and viability.
MAIN OUTCOME MEASURE(S)
Area under receiver operating characteristic curve, sensitivity, specificity, and accuracy of first trimester pregnancy outcome.
RESULT(S)
In 230 pregnancies, the combination of trees to maximize sensitivity and specificity resulted in 73% specificity (95% confidence interval (CI) 0.65-0.80) and 31% sensitivity (95% CI 0.21-0.43) for viability. Similar methods had 21% sensitivity (95% CI 0.12-0.32) and 33% specificity (95% CI 0.26-0.41) for location. Activin A, Glyc, and A Disintegrin And Metalloprotease-12 definitively classified pregnancy location in 29% of the sample with 100% accuracy for EP. Progesterone and PAPP-A classified the viability in 61% of the sample with 94% accuracy.
CONCLUSION(S)
Multiple marker panels can distinguish pregnancy location and viability in a subset of women at risk for early pregnancy complications. This strategy of combining markers to maximize sensitivity and specificity results in high accuracy in a subset of subjects. Activin A, ADAM12, and Glyc are the most promising markers for pregnancy location; P and PAPP-A for viability. | 10.1016/j.fertnstert.2016.08.044 |
pubmed_633_18793 | Pupil shape in vertebrates ranges from circular to vertical, with multiple phylogenetic shifts in this trait. Our analyses challenge the widely held view that the vertical pupil evolved as an adaptation to enhance night vision. On functional grounds, a variable-aperture vertical pupil (i) allows a nocturnal species to have a sensitive retina for night vision but avoid dazzle by day by adjusting pupil closure, and (ii) increases visual acuity by day, because a narrow vertical pupil can project a sharper image onto the retina in the horizontal plane. Detection of horizontal movement may be critical for predators that wait in ambush for moving prey, suggesting that foraging mode (ambush predation) as well as polyphasic activity may favour the evolution of vertical pupil shape. Camouflage (disruption of the circular outline of the eye) also may be beneficial for ambush predators. A comparative analysis in snakes reveals significant functional links between pupil shape and foraging mode, as well as between pupil shape and diel timing of activity. Similar associations between ambush predation and vertically slit pupils occur in lizards and mammals also, suggesting that foraging mode has exerted major selective forces on visual systems in vertebrates. | 10.1111/j.1420-9101.2010.02046.x |
pubmed_15_13369 | Myoclonic epilepsy in infancy (MEI) is a primary generalized epilepsy. According to the literature, the outcome of MEI is usually benign. Here we report a patient who developed myoclonic astatic epilepsy at age four, having been seizure free without antiepileptic drug treatment for 2 years after his recovery from MEI. At age four, a video-EEG-recording showed frequent head nodding (atonic seizures) and myoclonic astatic seizures associated with diffuse spikes or polyspikes and waves. The interictal EEG revealed frequent bursts of generalized 100-200 μV, 2-4 Hz spike-and-slow-wave complexes. Despite a general favorable outcome, more severe epilepsy syndromes may develop after MEI, and mental retardation is sometimes observed. Our case and the previous literature suggest that epilepsies following on from MEI often involve myoclonic seizures. | 10.1016/j.seizure.2012.01.011 |
pubmed_568_17775 | AIMS
The goal of the current study was to describe the results of an innovative standardized approach to prevent wound complications in patients with PAD sustaining fractures below the knee.
PATIENTS AND METHODS
In this retrospective case series, patients submitted to our institution with fractures below the knee, which were treated with endovascular recanalization of relevant stenosis or occlusions prior to definitive open reduction and fracture fixation between January 2015 and December 2019 were included.
RESULTS
Overall 23 patients (mean age 77 ± 9.8 years) were included in the current case series. In five patients (21.7 %) PAD was previously diagnosed. Endovascular interventions were performed 6.9 ± 2.5 days after fracture event and 2.5 ± 1.3 days prior to definitive surgical fixation of the lower limb fracture. After intervention 2 patients had one vessel, 10 patients two vessels and 11 patients three vessels for arterial perfusion of the lower limb. No interventional- radiology procedure related complications were observed. In this case series only two wound infections (8.7 %) occurred.
CONCLUSION
Endovascular intervention prior to surgical fixation resulted in a low complication rate after surgical fixation of fractures below the knee in patients with PAD. These results emphasize the crucial role of limb perfusion for adequate wound healing in lower limb fractures. Therefore, examination of limb perfusion should be an integral part of preoperative preparation of patients at high risk for PAD presenting with fractures below the knee. Endovascular recanalization seems to be an appropriate method to prevent wound complications. | 10.1016/j.injury.2021.04.039 |
pubmed_12_15156 | This paper provides a detailed description of a gustometer designed and constructed in our laboratory for psychophysical taste testing in rats. The gustometer features: a) 12 stimulus channels, b) the ability to deliver a specified volume of a taste stimulus per lick (e.g., 5 microliters), c) the accurate measurement of immediate licking responses, d) an automatic drinking spout cleaning mechanism for use between taste trials, and e) complete computer control and analysis. Complete plans and electronic schematics are included. In addition, results from contamination tests are presented verifying the reliability of the stimulus delivery system. The usefulness and versatility of this apparatus in a variety of behavioral tasks is discussed. | 10.1016/0031-9384(90)90099-p |
pubmed_1004_23093 | BACKGROUND
The monitoring of children with asthma in primary care is based on the occurrence and frequency of asthma symptoms. We questioned whether the current approach is adequate to identify all children in whom a sufficient level of asthma control is not achieved.
AIM
The aim of this study is to illustrate that in some children asthma was incorrectly considered controlled, because the children failed to report current symptoms of asthma.
PATIENTS AND METHODS
One hundred and nineteen children were identified with recent wheezing plus moderate or severe airway hyperresponsiveness. We analyzed whether these children reported current symptoms of asthma (as normally questioned during a routine visit).
RESULTS
In 20 children (18%) current asthma symptoms were absent despite moderately or severe airway hyperresponsiveness and wheezing in the last year. In addition, the usage of controller medication was very poor.
CONCLUSION
We conclude that the general practitioner has insufficient tools to adequately assess asthma control in all children. The assessment of airway hyperresponsiveness as an additional guide to manage asthma in children in general practice is recommended. In this way, better asthma control can be achieved. | 10.1016/j.rmed.2008.03.008 |
pubmed_820_2322 | Fifty-eight garments were taped and searched for mid to dark blue wool fibres. These were then removed from the tapings, mounted on slides and examined using a high-power microscope (400x). A total of 2,740 blue wool fibres were identified and visible range microspectrophotometry (MSP) was performed on them. Three hundred independent blue wool populations were identified on 56 of the 58 garments searched. The lack of control fibres meant the spectral range of each population was unknown. The number of populations may have been underestimated by grouping together the fibres that had broad single peaks and a lack of distinguishing features in the spectra. Although blue wool is considered to be a common fibre type, 300 unique spectral shapes were identified by the use of microspectrophotometry alone. This demonstrates that the dyes used in the dyeing of blue wool are variable. Showing that many different populations of blue wool occur on a range of garments should ensure that the forensic scientist does not underestimate or understate the strength of evidence in cases where blue wool is found. Hopefully this work will enlighten scientists and enable them to also assess the true value of their findings when other commonly occurring fibres are encountered. | 10.1016/S1355-0306(05)71650-6 |
pubmed_288_18893 | Free proline amino acid is a natural cryoprotectant expressed by numerous organisms under low-temperature stress. Previous reports have suggested that complex assemblies underlie its functional properties. We investigate here aqueous proline solutions as a function of temperature using combinations of Raman spectroscopy, Rayleigh-Brillouin light scattering, and molecular dynamics simulations with the view to revealing the molecular origins of the mixtures' functionality as a cryoprotectant. The evolution of the Brillouin frequency shifts and line widths with temperature shows that, above a critical proline concentration, the water-like dynamics is suppressed and viscoelastic behavior emerges: Here, the Landau-Placzek ratio also shows a temperature-independent maximum arising from concentration fluctuations. Molecular dynamics simulations reveal that the water-water correlations in the mixtures depend much more weakly on temperature than does bulk water. By contrast, the water OH Raman bands exhibit strong red-shifts on cooling similar to those seen in ices; however, no evidence of ice lattice phonons is observed in the low-frequency spectrum. We attribute this primarily to enhanced proline-water hydrogen bonding. In general, the picture that emerges is that aqueous proline is a heterogeneous mixture on molecular length scales (characterized by significant concentration fluctuations rather than well-defined aggregates). Simulations reveal that proline also appears to suppress the normal dependence of water structure on temperature and preserves the ambient-temperature correlations even in very cold solutions. The water structure in cold proline solutions therefore appears to be similar to that at a higher effective temperature. This, coupled with the emergence of glassy dynamics offers a molecular explanation for the functional properties of proline as a cryoprotectant without the need to invoke previously proposed complex aggregates. | 10.1021/jp076713m |
pubmed_317_18117 | The herpes simplex virus type 1 (HSV-1) latency-associated transcript (LAT) encodes several microRNAs. One of these, miR-H2, overlaps and is antisense to the ICP0 gene and appears to decrease expression of the ICP0 protein. To determine if miR-H2 plays a role in the HSV-1 latency-reactivation cycle, we constructed a mutant, McK-ΔH2, in which this microRNA has been disrupted without altering the predicted amino acid sequence of ICP0. McK-ΔH2 produced increased amounts of ICP0. Although replication of McK-ΔH2 was similar to that of its wild-type (wt) McKrae parental virus in RS cells and mouse eyes, McK-ΔH2 was more neurovirulent in Swiss-Webster mice than McKrae based on the percent of mice that died from herpes encephalitis following ocular infection. In addition, using a mouse trigeminal ganglia (TG) explant model of induced reactivation, we show here for the first time that miR-H2 appears to play a role in modulating HSV-1 reactivation. Although the percent of TG from which virus reactivated by day 10 after explant was similar for McK-ΔH2, wt McKrae, and the marker-rescued virus McK-ΔH2Res, at earlier times, significantly more reactivation was seen with McK-ΔH2. Our results suggest that in the context of the virus, miR-H2 downregulates ICP0 and this moderates both HSV-1 neurovirulence and reactivation. | 10.1007/s13365-015-0319-1 |
pubmed_5_15893 | Recent mergers and downsizing of health care agencies have made resources for continuing education (CE) increasingly scarce. Nurse educators must demonstrate the effectiveness and sustainability of CE programs and establish the link between nursing professionalism and positive patient outcomes. The Pyramid Evaluation Model expands and enhances previous evaluation frameworks. Simple steps are outlined to evaluate CE programs and outcomes systematically and comprehensively through an impact model that examines goals, reviews program design, monitors program implementation, assesses outcomes and impact, and analyzes efficiency. | 10.3928/0022-0124-19990901-05 |
pubmed_561_3821 | BACKGROUND AND OBJECTIVES
Solvent/detergent-treated plasma (SDP) contains markedly lower protein S (PS) and plasmin inhibitor (PI) activity than standard fresh-frozen plasma (FFP). It has also been reported that SDP contains no alpha(1)-antitrypsin. Despite the lack of clinical data, it is suspected that SDP may be less effective than FFP in the treatment of complex coagulopathies. We therefore conducted a prospective trial to study the impact of SDP and FFP on haemostasis and fibrinolysis in complex coagulopathy after open-heart surgery.
MATERIALS AND METHODS
Patients received either 600 ml of SDP (n = 36) or 600 ml of FFP (n = 31) at an infusion rate of 30 ml/min. The following parameters were measured before treatment and 60 min after termination of plasma infusion: prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen, factor VIII, antithrombin, protein C (PC), free PS and PS activity, prothrombin fragments F1+2 (F1+2), D-dimers (DD), fibrinogen degradation products (FDP), plasmin-plasmin inhibitor complexes (PPI), plasminogen, PI and alpha(1)-antitrypsin.
RESULTS
The rise in fibrinogen, factor VIII, antithrombin, PC, free PS, alpha(1)-antitrypsin and plasminogen, and the decrease in PT and APTT, did not significantly differ between the two study arms. However, PS activity did not increase after SDP infusion but did show a significant elevation after infusion with FFP. PI declined significantly after SDP and remained uninfluenced by FFP. Neither SDP nor FFP had any significant influence on F1+2, DD or FDP. However, a significant decrease in PPI levels caused by both types of plasma indicated a reduction in hyperfibrinolysis. Clinical haemostasis evaluation revealed no significant difference between the two treatment regimens. No adverse reactions were observed.
CONCLUSION
With the exception of PS and PI, SDP and FFP improved haemostasis and fibrinolysis to a similar degree. The clinical significance of these findings has to be determined in patients with severe acquired PS and PI deficiency requiring plasma transfusions. | 10.1046/j.1423-0410.2002.00129.x |
pubmed_249_104 | The Ipomopsis aggregata species complex (Polemoniaceae) includes species pairs that hybridize readily in nature as well as pairs that meet along contact zones with no apparent hybridization. Artificial hybrids can be made between I. aggregata and I. arizonica, yet morphological intermediates between these two species have not been observed in natural populations. This apparent lack of hybridization is perplexing given that plants of the two species often grow within a few metres of each other and both species have red flowers visited by the same species of hummingbirds. We used trained hummingbirds to examine pollen transfer within and between species. We also hand-pollinated flowers to examine paternal success of heterospecific and conspecific pollen, testing paternity with electrophoretic examination of seeds. Hummingbirds were not simply better at transferring pollen within than between species. Instead, I. arizonica was a better pollen donor so that considerable pollen transfer was observed from I. arizonica to I. aggregata, but very little in the opposite direction. Conversely, once pollen arrived at stigmas, I. arizonica pollen performed very poorly on I. aggregata pistils. However, pollen from I. aggregata could, in some cases, sire seeds on I. arizonica. We hypothesize that hybrids are scarce in nature, in part, because of asymmetric barriers to reproduction: little pollen transfer in one direction and poor pollen performance in the other. | pubmed_249_104 |
pubmed_578_11776 | OBJECTIVES
To estimate the rate of corneal erosion coupled with gram-negative bacterial contamination of contact lenses and compare this with the rate of microbial keratitis (MK) with contact lenses.
METHODS
The rate of corneal erosion and contact lens contamination by gram-negative bacteria were calculated from several prospective trials. These rates were used to calculate the theoretical rate of corneal erosion happening at the same time as wearing a contact lens contaminated with gram-negative bacteria. This theoretical rate was then compared with the rates of MK reported in various epidemiological and clinical trials.
RESULTS
Corneal erosions were more frequent during extended wear (0.6-2.6% of visits) compared with daily wear (0.01-0.05% of visits). No corneal erosions were observed for lenses worn on a daily disposable basis. Contamination rates for lenses worn on a daily disposable basis were the lowest (2.4%), whereas they were the highest for low Dk lenses worn on an extended wear basis (7.1%). The estimated rate of corneal erosions occurring at the same time as wearing lenses contaminated with gram-negative bacteria was the lowest during daily wear of low Dk lenses (1.56/10,000 [95% CI: 0.23-10.57]) and the highest during extended wear of high Dk lenses (38.55/10,000 [95% CI: 24.77-60.04]). These rates were similar in magnitude to the rates reported for MK of different hydrogel lenses worn on differing wear schedules.
CONCLUSION
The coincidence of corneal erosions during lens wear with gram-negative bacterial contamination of lenses may account for the relative incidence of MK during lens wear with different lens materials and modes of use. | 10.1097/ICL.0b013e3181f57b05 |
pubmed_58_840 | Despite public knowledge of advanced directives and end-of-life wishes, desire for control over destiny often conflicts with the reality of end-of-life presentation. Recognized as best practice by both the Emergency Nurses Association and the American College of Emergency Physicians, family presence during resuscitation can actually prevent unintended harm to patients and their families. | 10.1097/HNP.0000000000000264 |
pubmed_179_4047 | Trichosporon asahii is a pathogenic fungus that causes severe, deep-seated fungal infections in neutropenic patients. Elucidating the infection mechanisms of T. asahii based on genetic studies requires a specific gene-targeting system. Here, we established an efficient gene-targeting system in a highly pathogenic T. asahii strain identified using the silkworm infection model. By comparing the pathogenicity of T. asahii clinical isolates in a silkworm infection model, T. asahii MPU129 was identified as a highly pathogenic strain. Using an Agrobacterium tumefaciens-mediated gene transfer system, we obtained a T. asahii MPU129 mutant lacking the ku70 gene, which encodes the Ku70 protein involved in the non-homologous end-joining repair of DNA double-strand breaks. The ku70 gene-deficient mutant showed higher gene-targeting efficiency than the wild-type strain for constructing a mutant lacking the cnb1 gene, which encodes the beta-subunit of calcineurin. The cnb1 gene-deficient mutant showed reduced pathogenicity against silkworms compared with the parental strain. These results suggest that an efficient gene-targeting system in a highly pathogenic T. asahii strain is a useful tool for elucidating the molecular mechanisms of T. asahii infection. | 10.1038/s41598-021-97287-3 |
pubmed_673_13349 | The paper is a review of recent work with blastokinin, a uterine-specific protein of rabbit, and includes consideration of patterns of synthesis, induction by progestagens, metal-binding capacity, translation of its RNA message, possible changes in the molecule, and comparison with the "cone" protein of the oviduct. Other uterine proteins have been identified in the rabbit by their enzymatic or hormonal activity and shown to be distinct from blastokinin though present in the uterine lumen at the same time. Proteins which are temporally or chemically analogous to blastokinin in other species are discussed, including the question of whether a blastokinin-like protein occurs in women. Discussion of the comparative significance of such proteins must await a clearer definition of their function. | pubmed_673_13349 |
pubmed_788_18802 | UNLABELLED
SwS, based on a statistical analysis of crystallographic structures deposited in the NDB, is designed to provide an exhaustive overview of the solvation of nucleic acid structural elements through the generation of 3D solvent density maps. A first version (v1.0) of this web service focuses on the interaction of DNA, RNA and hybrid base pairs linked by two or three hydrogen bonds with water, cations and/or anions. Data provided by SwS are updated on a weekly basis and can be used by: (i) those involved in molecular dynamics simulation studies for validation purposes; (ii) crystallographers for help in the interpretation of solvent density maps; and all those involved in (iii) drug design and, more generally, in (iv) nucleic acid structural studies. SwS provides also statistical data related to the frequency of occurrence of different types of base pairs in crystallographic structures and the conformation of the involved nucleotides. This web service has been designed to allow a maximum of flexibility in terms of queries and has also been developed with didactic considerations in mind.
AVAILABILITY
http://www-ibmc.u-strasbg.fr/arn/sws.html | 10.1093/bioinformatics/btm067 |
pubmed_548_16708 | BACKGROUND
Multiple studies have established the superior diagnostic accuracy of video capsule endoscopy (VCE) for the diagnosis of small bowel (SB) Crohn's disease (CD). However, data on the clinical impact of VCE in patients with established CD are scarce. The aim of this study was to examine the impact and safety of VCE on the clinical management of patients with established CD.
METHODS
A retrospective, multicenter, cross-sectional study. The study cohort included consecutive patients with established SB CD who underwent VCE in 4 tertiary referral centers (1 Canada, 1 Sweden, and 2 United Kingdom) from January 2008 to October 2013. Patients were excluded if VCE was performed as a part of the initial diagnostic workup. The presence of SB mucosal inflammation was quantified using the Lewis score. Inflammatory biomarkers (C-reactive protein and fecal calprotectin) were measured and correlated with the Lewis score.
RESULTS
The study included 187 patients. No SB inflammation was observed in 28.4%, mild-to-moderate inflammation in 26.6%, and moderate-to-severe inflammation in 45% of the patients (median Lewis score, 662; range, 0-6400). A change in management was recommended in 52.3% of the patients based on VCE findings. Elevated C-reactive protein, fecal calprotectin, or the combination of both were poorly correlated with significant SB inflammation. SB capsule retention occurred in 4 patients (2.1%).
CONCLUSIONS
VCE in patients with established CD is safe, and the results often have a significant clinical impact. VCE should not be limited to CD patients with positive inflammatory markers because their predictive value for significant SB inflammation is poor. | 10.1097/MIB.0000000000000255 |
pubmed_664_5965 | In our previous work, we found that synephrine has six conformers in the gas phase, while adrenaline, which is a catecholamine and has the same side chain as synephrine, has been reported to have only two conformers. To determine the conformational geometries of synephrine, we measured resonance enhanced multiphoton ionization, ultraviolet-ultraviolet hole burning, and infrared dip spectra by utilizing the laser desorption supersonic jet technique. By comparing the observed infrared spectra with theoretical ones, we assigned geometries except for the orientations of the phenolic OH group. Comparison between the determined structures of synephrine and those of 2-methylaminno-1-phenylethanol, which has the same side chain as synephrine but no phenol OH group, leads to the conclusion that the phenolic OH group in synephrine does not affect the conformational flexibility of the side chain. In the case of adrenaline, which is expected to have 12 conformers if there are no interactions between the catecholic OH groups and the side chain, some interactions possibly exist between them because only two conformations are observed. By estimation of the dipole-dipole interaction energy between partial dipole moments of the catecholic OH groups and the side chain, it was concluded that the dipole-dipole interaction stabilizes specific conformers which are actually observed. | 10.1021/jp205267c |
pubmed_666_13650 | Insect intraspecific olfactory communication occurs in a complex sensory environment. Here we present recent results on how the olfactory system extracts specific information from a sensory background, and integrates it with complementary information to improve odor source localization. Recent advances on mechanisms of olfactory mixture processing, multi-modal integration, as well as plasticity of sensory processing are reviewed. Significant progress in the understanding of neural coding and molecular bases of olfaction reinforce our perception of the tremendous adaptability of insects to a changing environment. However several reports demonstrate that anthropogenic environmental perturbations interfere with insect olfactory communication and might as a consequence significantly alter the functioning of ecosystems and agroecosystems. | 10.1016/j.cois.2020.04.004 |
pubmed_824_6218 | AIMS
To determine the frequency of increasing levels of stress hyperglycemia and its associated complications in surgery patients without a history of diabetes.
METHODS
We reviewed hospital outcomes in 1971 general surgery patients with documented preoperative normoglycemia [blood glucose (BG) <140mg/dL] who developed stress hyperglycemia (BG >140mg/dL or >180mg/dL) within 48h after surgery between 1/1/2010 and 10/31/2015.
RESULTS
A total of 415 patients (21%) had ≥1 episode of BG between 140 and 180mg/dL and 206 patients (10.5%) had BG>180mg/dL. The median length of hospital stay (LOS) was 9days [interquartile range (IQR) 5,15] for BG between 140 and 180mg/dL and 12days (IQR 6,18) for BG>180mg/dL compared to normoglycemia at 6days (IQR 4,11), both p<0.001. Patients with BG 140-180mg/dL had higher rates of complications with an odds ratio (OR) of 1.68 [95% confidence interval (95% CI) 1.15-2.44], and those with BG>180mg/dL had more complications [OR 3.46 (95% CI 2.24-5.36)] and higher mortality [OR 6.56 (95% CI 2.12-20.27)] compared to normoglycemia.
CONCLUSION
Increasing levels of stress hyperglycemia are associated with higher rates of perioperative complications and hospital mortality in surgical patients without diabetes. | 10.1016/j.jdiacomp.2017.11.010 |
pubmed_556_15286 | PURPOSE
The primary aim of this study was to examine the pattern of associations among PD patient and caregiver sleep problems, caregiver burden, and caregiver life satisfaction. A secondary aim was to assess whether the pattern of associations differed between Mexican and U.S. caregivers.
MATERIALS AND METHODS
Analyses were performed on data obtained from 253 caregivers (M age = 59.92). A composite score was produced for caregiver and patient sleep problems. The Zarit Burden Interview and Satisfaction with Life Scale measured caregiver burden and life satisfaction, respectively. A structural equation model with an invariance design was developed to examine and compare the pattern of associations.
RESULTS
The model was generally invariant across U.S. and Mexican caregivers. Three significant indirect effects were found: caregiver sleep problems were negatively associated with life satisfaction via caregiver burden (p = 0.003); PD patient sleep problems were positively related to caregiver burden via caregiver sleep problems (p = 0.005) and life satisfaction via caregiver burden and caregiver sleep problems (p = 0.002).
CONCLUSIONS
PD patient sleep problems were associated with caregiver sleep problems, leading to increased burden in caregivers and poorer life satisfaction. The findings highlight a potential opportunity for empirically supported sleep interventions.Implications for rehabilitationParkinson's disease is a progressive neurological condition that impacts patient and caregiver quality of life.Patient sleep problems contribute to greater caregiver burden, sleep problems, and reduced life satisfaction.The findings suggest patient and caregiver sleep may be a worthwhile target for intervention in order to reduce risk of caregiver burden and improve life satisfaction. | 10.1080/09638288.2020.1814878 |
pubmed_962_985 | A new instrument for coniotomy was developed and tested with cadaver experiments. The instrument should be simple, easy to handle, and should not have the various drawbacks of the existing devices. The new instrument was tested by 17 medical students and medical doctors on fresh human cadavers. We measured the time necessary for performing a successful experiment. It lasted 5-28 sec (mean value 22 sec) depending on the experience of the people carrying out the tests. This time is much shorter than with other existing instruments tested under experimental conditions. The instrument consists of a tube and a trocar with a small knife on the tip. The knife is used to incise the skin over the cricothyroid ligament and to perforate this ligament in sagittal position. The tube is provided with a plastic stripe, which limits the depth of the entrance of the instrument into the larynx and can also be used to attach the tube to the neck of the patient. After entering the larynx, the tube can be connected to an inflating bag. The correct seat of the tube was tested by inflation, with a calibrated probe or with laryngoscopy. The results of our tests encourage the development of this new instrument for industrial production. | 10.1002/ca.20263 |
pubmed_739_7812 | Recent research on the effects of selective 5-HT1A receptor antagonists in animal models of anxiety has yielded inconsistent findings. In the present study, the behavioural effects of the novel 5-HT1A receptor antagonist, 4-(2'-methoxy-phenyl)-1-[2'-(n-2"-pyridinyl) -p-iodobenzamido]-ethyl-piperazine (p-MPPI), were examined in male mice using an ethological version of the elevated plus-maze test. Results show that at lower doses (0.5-4.5 mg/kg), p-MPPI produced a significant and dose-related anxiolytic profile on both conventional (open arm avoidance) and ethological (risk assessment) measures. However, these effects were lost at a higher dose (13.5 mg/kg) which, instead, increased grooming and immobility. The behavioural profile of p-MPPI is contrasted with those previously obtained with other 5-HT1A receptor ligands (agonists, partial agonists and antagonists), and it is suggested that 5-HT1A receptor antagonists may possess therapeutic advantages in anxiety disorders. | 10.1007/s002130050202 |
pubmed_1005_2631 | Proline hydroxylation is a critical cellular mechanism regulating energy homeostasis and development. Our previous study identified and validated Bromodomain-containing protein 4 (BRD4) as a proline hydroxylation substrate in cancer cells. Yet, the regulatory mechanism and the functional significance of the modification remain unknown. In this study, we developed targeted quantification assays using parallel-reaction monitoring and biochemical analysis to identify the major regulatory enzyme of BRD4 proline hydroxylation. We further performed quantitative interactome analysis to determine the functional significance of the modification pathway in BRD4-mediated protein-protein interactions and gene transcription. Our findings revealed that PHD2 is the key regulatory enzyme of BRD4 proline hydroxylation and the modification significantly affects BRD4 interactions with key transcription factors as well as BRD4-mediated transcriptional activation. Taken together, this study provided mechanistic insights into the oxygen-dependent modification of BRD4 and revealed new roles of the pathway in regulating BRD4-dependent gene expression. | 10.1074/mcp.RA119.001535 |
pubmed_658_7415 | BACKGROUND AND OBJECTIVES
To assess the potential use of diode laser soldering to improve mechanical stability of middle ear reconstruction. The diode laser with a biological solder may offer benefits over traditional methods. We evaluated the strength of soldered bonds and a means to apply such a technique in the human middle ear.
STUDY DESIGN/MATERIALS AND METHODS
The strength of soldered junctions using fascia, cartilage, bone, and hydroxyappatite was evaluated in vitro. A diode laser (810-nm wavelength) and 50% albumin with 0.1% indocyanine green dye was used. Soldered bonds were compared to those obtained with adhesive alone. A fiberoptic delivery system was evaluated. Ten hydroxyappatite prostheses were soldered to the stapes in human cadaver temporal bones, and the force required to disrupt the bonds were measured.
RESULTS
Statistically significant greater strength was obtained with soldering. Ossicular prostheses can be effectively secured to the stapes in a cadaver model.
CONCLUSIONS
Soldering techniques show promise in middle ear reconstruction. | 10.1002/lsm.10091 |
pubmed_1077_22372 | The gas injection line of the latest spherical aberration-corrected environmental transmission electron microscope has been modified for achieving real-time/atomic-scale observations in moisturised gas atmospheres for the first time. The newly developed Wet-TEM system is applied to platinum carbon electrode catalysts to investigate the effect of water molecules on the platinum/carbon interface during deactivation processes such as sintering and corrosion. Dynamic in situ movies obtained in dry and 24% moisturised nitrogen environments visualize the rapid rotation, migration and agglomeration of platinum nanoparticles due to the physical adsorption of water and the hydroxylation of the carbon surface. The origin of the long-interconnected aggregation of platinum nanoparticles was discovered to be a major deactivation process in addition to conventional carbon corrosion. | 10.1088/0957-4484/25/42/425702 |
pubmed_481_4058 | This Directory of Databases with significant holdings of primarily bibliographic references to complementary and alternative medicine research resources has been compiled to facilitate access to the widely scattered data and literature. The Directory is directly accessible from the Web site of the Richard & Hinda Rosenthal Center for Complementary and Alternative Medicine at Columbia University's CPMCNet (http://cpmcnet.columbia.edu/dept/rosenthal/). General selection criteria and a brief description of content, access, or contact details are given for each of the 56 databases. Thirty-five of the databases are available online over the Internet and of these, 17 are freely, publicly available. There are 13 search services and a further 8 databases available in a variety of formats. | 10.1089/acm.1997.3.179 |
pubmed_187_7115 | We have studied the role of phosphorylation of the human oestrogen receptor (hOR; otherwise known as hER) at serine-167, which has been identified previously as the major oestrogen-induced phosphorylation site. We have tested transactivation by the hOR in yeast and cell-free transcription assays, and shown that mutation of serine-167 results in a 70% decrease in hOR-dependent transcription. Furthermore we explored the functional significance of phosphorylation at this site by hormone binding and DNA binding. DNA binding affinity was 10-fold lower when serine-167 was changed to alanine in the hOR. Cell-free transcription experiments showed that casein kinase II is the enzyme responsible for oestradiol-dependent phosphorylation of the hOR at serine-167. This suggests that a conformational change of the hOR must occur upon hormone binding that exposes serine-167 to casein kinase II, resulting in transactivation of oestrogen-responsive genes. | 10.1042/bj3260149 |
pubmed_872_22260 | A new computerized semi-automatic method for left ventricular chamber segmentation is presented. The left ventricle is imaged by real-time three-dimensional echocardiography. This real-time data acquisition method allows accurate evaluation of chamber size and shape, even in case there are cavities with irregular geometry. The surface detection model is based on a partial differential equation that propagates interfaces with curvature dependent speeds. The equation is solved by applying numerical methods for conservation laws. The method consists of one step only. Initial conditions are manually established on a small subset of slices of the entire volume. The solution obtained is a surface corresponding to the surface between LV cavity and LV endocardium. This mathematical model is applied to sequences of frames of human hearts (volume range: 34-109 ml) imaged by real-time 3D echocardiography. Volume estimates show an excellent correlation with those obtained by manual tracing (r=0.99). | pubmed_872_22260 |
pubmed_44_3934 | BACKGROUND
Sleep-disordered breathing may affect coronary artery disease, so patients treated by percutaneous transluminal coronary angioplasty were studied to investigate the relationship between nocturnal oxygen desaturation (NOD) and the loss index.
METHODS AND RESULTS
The nocturnal oxygen desaturation index (ODI) was determined by means of a pulse oximeter in 35 patients with coronary artery disease treated by stent placement. The patients were divided into 3 groups according to ODI: <5 events/h (group N, n=6), between 5 and 14 events/h (group A, n=19), and >or=15 events/h (group B, n=10). The relationship between the ODI and loss index was examined in each group. The loss index, 0.27+/-0.23 in group N, 0.30+/-0.27 in group A, and 0.70+/-0.32 in group B, differed significantly between groups N and B (p=0.007). In all patients, the loss index showed a significant positive correlation with the ODI (R=0.585, p=0.002).
CONCLUSIONS
These findings suggest that NOD may be an important contributor to coronary restenosis in patients treated with stent placement. | 10.1253/circj.69.1320 |
pubmed_915_18708 | PURPOSE
To systematically review the literature for radiographic prevalence of osteoarthritis (OA) at a minimum of 10 years following anterior cruciate ligament (ACL) reconstruction (ACLR) with anatomic vs. non-anatomic techniques. It was hypothesized that the incidence of OA at long-term follow-up would be lower following anatomic compared to non-anatomic ACLR.
METHODS
A systematic review was performed by searching PubMed, MEDLINE, EMBASE, and the Cochrane Library, for studies reporting OA prevalence by radiographic classification scales at a minimum of 10 years following ACLR with autograft. Studies were categorized as anatomic if they met or exceeded a score of 8 according the Anatomic ACL Reconstruction Scoring Checklist (AARSC), while those with a score less than 8 were categorized as non-anatomic/non-specified. Secondary outcomes included graft failure and measures of knee stability (KT-1000, Pivot Shift) and functional outcomes [Lysholm, Tegner, subjective and objective International Knee Documentation Committee (IKDC) scores]. OA prevalence on all radiographic scales was recorded and adapted to a normalized scale.
RESULTS
Twenty-six studies were included, of which 5 achieved a score of 8 on the AARSC. Using a normalized OA classification scale, 87 of 375 patients (23.2%) had diagnosed OA at a mean follow-up of 15.3 years after anatomic ACLR and 744 of 1696 patients (43.9%) had OA at mean follow-up of 15.9 years after non-anatomic/non-specified ACLR. The AARSC scores were 9.2 ± 1.3 for anatomic ACLR and 5.1 ± 1.1 for non-anatomic/non-specified ACLR. Secondary outcomes were relatively similar between techniques but inconsistently reported.
CONCLUSIONS
This study showed that anatomic ACLR, defined as an AARSC score ≥ 8, was associated with lower OA prevalence at long-term follow-up. Additional studies reporting long-term outcomes following anatomic ACLR are needed, as high-level studies of anatomic ACLR are lacking. The AARSC is a valuable resource in performing and evaluating anatomic ACLR. Anatomic ACLR, as defined by the AARSC, may reduce the long-term risk of post-traumatic OA following ACL injury to a greater extent than non-anatomic ACLR.
LEVEL OF EVIDENCE
IV. | 10.1007/s00167-019-05665-2 |
pubmed_1109_19576 | Malnutrition has dominated Bangladesh development, encouraged by the Bangladesh Integrated Nutrition Programme under the first Sector-Wide Approach (SWAp) World Health Organization, and the United Nations Food and Agriculture Organization. To date, all the SWAps for health, nutrition and population well-being have identified malnutrition as a priority. Donors, United Nations organizations and non-governmental organizations provide extensive support to prevent and tackle malnutrition in the country. The government has delineated an effective policy response to the high prevalence of undernutrition. Bangladesh has a wide range of policies encouraging appropriate infant and young child feeding practices, 6 months of paid maternity leave in the public sector, school meals for vulnerable communities, micronutrient supplementation interventions and more. However, almost all of these efforts address the undernutrition aspect of malnutrition, neglecting the other form of malnutrition - overnutrition. Trend data from national surveys show steady increases in overweight and steady decreases in underweight among women of reproductive age. This paper sheds light on the trend data, showing the transition from under- to overnutrition and the double burden of malnutrition among Bangladeshi women of reproductive age. It also discusses the national policy and programme responses to overweight and obesity in Bangladesh among the same population. | 10.1111/obr.12100 |
pubmed_647_11377 | On the basis of the known literature and our own results on patients' suicide, reflections are made with regard to the group of suicide cases with bipolar affective illnesses that commit suicide during inpatient psychiatric treatment. In our own studies, we diagnosed mania in as many as 8% of all suicide cases. Risk factors for suicidal behavior in bipolar affective disorder are discussed, especially in terms of psychopathology, and the social consequences of the disease are discussed. | 10.1080/13811110590929451 |
pubmed_118_11276 | BACKGROUND
Direct-acting antivirals (DAA) for the treatment of hepatitis C virus (HCV) have drastically improved outcomes but are also very costly. For this reason, priority for treatment is often given to patients with a higher fibrosis score at baseline by payers and providers rather than treating all eligible patients. Simulation studies have suggested that waiting to treat patients until fibrosis 3-4 may be more costly and result in worse outcomes; however, real-world implications are unknown.
OBJECTIVE
To determine drug costs and outcomes for treating hepatitis C in patients with fibrosis scores of 0-2 and 3-4 at baseline in a real-world ambulatory care setting.
METHODS
A total of 322 patients at 36 clinical sites in Massachusetts with HCV genotype 1-4 and a prescription for at least 1 DAA medication between May 2011 and October 2015 were included. Retrospective and prospective chart reviews were completed by the primary investigator. Data were collected through April 2016. The primary outcome for the study was to determine the mean drug cost per sustained virologic response (SVR) achieved for patients with fibrosis scores of 0-2 and 3-4. Drug costs were calculated using average wholesale price and only included the cost of HCV medications, not for adjunctive medications, blood work, hospitalizations, anticipated complications, or any other projected medical costs.
RESULTS
The mean ± SD (median) drug cost per patient was $130,391 ± 46,787 (113,400) and completed treatment duration was 15.0 ± 8.9 (12) weeks. The mean drug cost per SVR was $155,662 for all patients with a mean drug cost per SVR of $122,452 and $178,401 for patients with fibrosis scores of 0-2 and 3-4, respectively. SVR rates were 83.5% (269/322) for all patients and 92.2% (107/116) and 78.6% (162/206) for patients with fibrosis scores of 0-2 and 3-4, respectively. Ledipasvir/ sofosbuvir; sofosbuvir + ribavirin; ledipasvir/sofosbuvir + ribavirin; sofos-buvir + interferon + ribavirin; boceprevir + interferon + ribavirin; sofosbu-vir + simeprevir; and telaprevir + interferon + ribavirin had a mean drug cost per SVR of $123,559; $153,347; $157,969; $184,800; $248,640; $251,550; and $373,333; respectively.
CONCLUSIONS
Real-world knowledge about outcomes and drug costs may influence future decisions. Further studies are needed to evaluate emerging treatment options and to reflect changes in treatment guidelines.
DISCLOSURES
No outside funding supported this study. The authors report no conflicts of interest. Data in this study were presented as a poster at the ASHP Midyear Clinical Meeting; New Orleans, Louisiana; December 9, 2015; at the Massachusetts Society of Health-System Pharmacists Annual Meeting; Newton, Massachusetts; April 12, 2016; and at Eastern States Conference for Pharmacy Residents and Preceptors; Hershey, Pennsylvania; May 2, 2016. Study concept and design was primarily contributed by Bach, along with Zaiken. Bach took the lead in data collection, data interpretation, and preparation of the manuscript, along with Zaiken. | 10.18553/jmcp.2016.22.12.1437 |
pubmed_878_22578 | BACKGROUND
There is growing evidence that femoroacetabular impingement is a potentially important risk factor for the development of early idiopathic osteoarthritis in the nondysplastic hip. Understanding of affected joint kinematics is a basic prerequisite in the evaluation of mechanical disorders in a clinical and research oriented setting. The aim of the present study was to compare pelvifemoral kinematics between subjects diagnosed with femoroacetabular impingement and healthy controls.
METHODS
The authors collected motion data of the femur and pelvis on a total of 43 hips - 19 cam impingement hips and 24 healthy controls - using a validated electromagnetic tracking device. The pelvifemoral rhythm in supine position was defined during both active and passive hip flexion and statistically compared between both groups.
FINDINGS
A significant increase in posterior pelvic rotation was observed during active hip flexion in the femoroacetabular impingement group compared with the control group (P<0.001). During passive hip flexion, however, posterior pelvic rotation between the impingement group and the controls did not differ significantly (P=0.628).
INTERPRETATION
Posterior pelvic rotation during active high-end hip flexion is increased in femoroacetabular impingement, indicating the presence of an active compensational mechanism that decreases the extent of harmful joint conflict during high-flexion activities. | pubmed_878_22578 |
pubmed_173_4762 | This paper examines the ability of countries in Central and Eastern Europe (CEE) to ensure appropriate protection of research participants in the field of increasingly globalizing biomedical research. By applying an analytical framework for identifying gaps in policies and programs for human subjects protection to four countries of CEE-Belarus, Latvia, Lithuania, and Poland, substantial gaps in the scope and content of relevant policies and major impediments to program performance have been revealed. In these countries, public policies on the protection of research participants lack consistency and reliable mechanisms for their implementation. Impediments to program performance most often relate to inadequacies in the national research ethics systems with regard to organizational structure, budgetary support, supervision, and training. The level of research ethics capacity varies from country to country and depends on socio-economic and political factors of post-communist transition. The breadth and depth of the problems identified suggest that the current level of protection for research participants in CEE might be inadequate to the challenges posed by the globalization of biomedical research. In CEE countries, there is a need for strengthening research ethics capacity through modification of relevant policies and improvement of program management. The differences among the countries call for further research on identifying the best approaches for filling the gaps in the policies and programs aimed at ensuring effective protection of research participants. | 10.1007/s11948-015-9723-4 |
pubmed_480_6188 | As an extensively studied quality control system, autophagy is responsible for clearance of dysfunctional organelles and damaged marcomolecules in cells. In addition to its biological recycling function, autophagy plays a significant role in the pathogenesis of metabolic syndromes such as obesity and diabetes. In particular, metabolic disorders contribute to cardiovascular disease development. As energy required to maintain cardiac cells functional is immense, disturbances in the balance between anabolic and catabolic metabolism possibly contribute to cardiovascular disorders. Therefore, an urgent need to expand our knowledge on the role of autophagy on the metabolic regulation of hearts emerges. In this review, the potential relationship between autophagic activity and cardiac metabolism is explored and we also discuss how dysregulated autophagy leads to severe cardiac disorders from the perspective of metabolic control. | 10.1002/cbin.10626 |
pubmed_584_4231 | We present a theory for the transport of molecules adsorbed in slit and cylindrical nanopores at low density, considering the axial momentum gain of molecules oscillating between diffuse wall reflections. Good agreement with molecular dynamics simulations is obtained over a wide range of pore sizes, including the regime of single-file diffusion where fluid-fluid interactions are shown to have a negligible effect on the collective transport coefficient. We show that dispersive fluid-wall interactions considerably attenuate transport compared to classical hard sphere theory. | 10.1103/PhysRevLett.91.126102 |
pubmed_977_7227 | Fluoride is present in groundwater and drinking water across the world and plays crucial roles in regulating oral health. Although a 0.7-1.2 ppm concentration of fluoride in water supplies is deemed optimal for enamel development and dental health, its higher concentration causes endemic fluorosis, acute gastric, urolithiasis, and kidney infection, making the detection of fluoride highly important. However, the standard methods of fluoride detection, such as potentiometric or ion-selective detection, require specific instruments and often pre-treatment before analysis and do not offer the scope for on-site detection. Herein, we report the development of a polydiacetylene (PDA) grafted poly(vinylidene fluoride) (PVDF) membrane for sensitive solid-phase detection of fluoride. The sensors were prepared by functionalizing PDA with the boronic acid functionality as the F- recognition unit and impregnating it on PVDF strips. Upon exposure to fluoride, the strips displayed a visible color change from blue to red. The solid-phase sensor showed selectivity against common anions and can detect F- ions as low as 0.11 ppm. The real sample analysis in water and toothpaste and validation by ion chromatography demonstrate its potential application as an efficient lab-on-membrane for fluoride ions. | 10.1039/d2an00848c |
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