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pubmed_373_7395 | A compact system is presented, which can continuously monitor the occurrence of fracture site movement in patients with tibial shaft fractures treated with an Orthofix external fixator allowing limited axial movement. The system comprises a microswitch and data logger board, which are both attached to the fixator. Each time the switch is closed by the movement of the fixator, the data logger records it as an event. The number of events per half hour is stored to the board's memory. The data logger can record the frequency of movement for at least a four-week period, at which time, the data can be transferred to a computer via a serial link. The system has been proven in a limited patient trial. The results highlight the variation in patient mobility. The significance of continuously monitoring the fracture site movement during the healing period is discussed. | 10.1016/s1350-4533(96)00068-9 |
pubmed_647_10542 | N-[2-(Diethylamino)ethyl]-5-[(Z)-(5-[18F]fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide, a new potential positron emission tomography tracer for imaging cancer tyrosine kinase, has been prepared by the nucleophilic substitution of the nitro-precursor N-[2-(diethylamino)ethyl]-5-[(Z)-(5-nitro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide with K18F/Kryptofix 2.2.2 followed by a simple chromatography methodology combined solid-phase extraction with high-performance liquid chromatography purification procedures in 15-25% radiochemical yields. | 10.1016/j.bmcl.2005.06.038 |
pubmed_1060_12098 | In 61 patients the effectiveness of imipenem in the treatment of chronic post-traumatic osteitis was examined. The diagnosis of post-traumatic osteitis was based on clinical and radiological signs of infection, as well as a positive bone culture from a surgical specimen. The average duration of treatment was 10 days with a dosage 3 X 500 mg imipenem daily. The most commonly identified pathogen was Staphylococcus aureus. In 75% of the cases an infection with Gram-positive pathogens was found. The majority of Gram-negative infections was caused by Pseudomonas aeruginosa. The rate of elimination was greater than 90% for both Gram-positive and Gram-negative bacteria. A definite cure was achieved in 80% of the reported cases, only four patients (7%) showed a recurrence of the infection. Allergic reactions or other adverse effects were not observed except for diarrhoea in four patients. The high rate of therapeutic effectiveness as well as the excellent toleration justify the use of imipenem in the treatment of chronic post-traumatic osteitis. | pubmed_1060_12098 |
pubmed_825_15080 | MO is a soft-tissue mass, reported only 3 times in the cervical paravertebral area in a search of the literature. We describe an additional case in a 10-year-old girl. We emphasize that in the unusual radial radiopaque roentgenographic image, a malignant tumor could be considered. We also stress that CT scanning can be of great value in establishing the diagnosis. The clinical types and the radiological and pathological features of MO are described in some detail and the "zonal" sign is described. | 10.1007/BF00194255 |
pubmed_1080_7464 | In order to clarify the minute reactions of endometrial adenocarcinoma to sex steroid hormones, especially Progesterone (P), two kinds of in vivo models with differing sex steroid hormone receptor content were transplanted into nude mice. Subsequently, Estrogen (E2) and P were administered alone or together. Sequential histopathological changes, tumor growth curve and volume doubling time were investigated as compared to the castrated control group. Growth rate was increased by E2 administration compared to controls for the model positive for the E2 receptor (ER) and negative for the P receptor (PR), with PR production confirmed in 1 of 3 mice. P produced a slight inhibition of growth, and the inhibitory effect of P was additive with E2. The histological findings consisted of dense solid masses of cells in the tumor in mice treated with E2. The cells decreased in number and in some foci, the tubular glands were cystic in P-treated mice. The number of tumor cells in mice treated with E2 and P was less than in mice given P alone because of a secretive function seen in the appearance of PAS positive granules in the glandular epithelium and degenerative change such as swelling. With the tumor negative for both ER and PR, on the other hand, there was little difference in tumor cell growth between the treated and control groups, and no inhibitory effect was observed after administration of P or coadministration of E2 and P. Histologically, findings with increased nuclear division of tumor cells suggestive of tumor cell growth were obtained after administration of E2 alone and coadministration of E2 and P. E2 exhibited cell growth promoting action in endometrial adenocarcinoma, whether or not ER was present, and P appeared to inhibit tumor cell growth in the presence of ER even when PR was absent. In short, it was suggested that P acted by some mechanism independent of PR. After coadministration of E2 and P, tumor cells were affected in a direction toward functional differentiation in the ER positive tumor. The inhibitory effect of P was obviously additive with E2 in this tumor, while it was suggested that in ER negative tumor, E2 alone promotes tumor cell growth. | pubmed_1080_7464 |
pubmed_659_3416 | Objective
To quantitatively evaluate the impaired perfusion status of patients with symptomatic internal carotid artery (ICA) steno-occlusive disease and to explore the risk factors of impaired perfusion with computed tomography perfusion (CTP).
Methods
The clinical and imaging data of 187 patients with ICA steno-occlusive disease were retrospectively analyzed. The ICA stenosis rate was divided into Grades I-IV (70-79%; 80-89%; 90-99%; 100%), and the circle of Willis was classified as four types (types I-IV). According to the literature, the value of cerebral blood flow/cerebral blood volume (CBF/CBV) of 7.55/min was used as cut-off to predict symptomatic patients. All patients were categorized into two groups: those with impaired perfusion [n = 99 (52.9%)] and those without impaired perfusion [n = 88 (47.1%)]. Symmetrical bilateral internal watershed areas were selected as the regions of interest (ROIs). Statistical analysis was made on the status of impaired perfusion and the risk factors of impaired perfusion.
Results
Univariate analysis revealed that systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), types of the circle of Willis, and clinical features at admission differed between the two groups (patients with or without impaired perfusion) (p < 0.05). Multiple logistic stepwise regression analysis showed that MAP [odds ratio (OR) = 0.946, 95% confidential interval (CI) = 0.917-0.974, p < 0.001] and type IV (type I vs. IV: OR = 4.987, 95% CI = 1.955-12.723, p = 0.001) at admission were independently associated with impaired perfusion in the internal watershed areas.
Conclusion
MAP and the type of circle of Willis at admission are independent risk factors associated with the impaired perfusion in patients with ICA steno-occlusive disease. | 10.3389/fneur.2022.801413 |
pubmed_987_17296 | Recent decades have witnessed flourishing prosperity of III-nitride emitters in solid-state lighting and high-resolution displays. As one of the widely used substrates, sapphire shows superiority for heteroepitaxial growth of III-nitride light-emitting diode (LED) structure, due to the advantages of stability, low cost, high mechanical strength, as well as mature fabrication technology. However, realization of efficient LEDs grown on sapphire substrate is impeded by high density of defects in epilayers and low light extraction efficiency. The emergence of patterned sapphire substrate (PSS) turns out to be a promising and effective technology to overcome these problems and enhance the LED performances. In this review, we first introduce the background and recent advances of PSS applied in III-nitride visible and ultraviolet LEDs are. Then, we summarize the fabrication methods of PSS, together with novel methods to define nanometre-scale patterned structures. We further demonstrate the effect of PSS that contributes to reduce the threading dislocation density (TDD) of epilayers in detail. Meanwhile, mechanism of light extraction efficiency enhancement by adopting PSS is presented based on numerical analysis. Next, we explore the influence of PSS structural parameters (e.g. pattern size, pattern shape and aspect ratio) on LED performances, spanning from visible to deep ultraviolet UV emission region. Finally, challenges and potential prospects in PSS for future LED development are proposed and forecasted as well. | 10.1039/d1nr08221c |
pubmed_764_9118 | We treated two children with intractable epilepsy with electroconvulsive therapy (ECT) for seizure control. One child showed a change in seizure pattern with treatment, which at greater intensity was also effective in stopping nonconvulsive status epilepticus. The other child showed a decrease in spontaneous seizure frequency during short-term treatment. These findings suggest a possible role for ECT in the management of intractable epilepsy in children who are not candidates for epileptic surgery. | 10.1212/wnl.49.5.1389 |
pubmed_498_14101 | C57BL/6 mice are known to be rather resistant to the induction of experimental chronic kidney disease (CKD) by 5/6-nephrectomy (5/6-Nx). Here, we sought to characterize the development of CKD and its cardiac and skeletal sequelae during the first three months after 5/6-Nx in C57BL/6 mice fed a calcium- and phosphate enriched diet (CPD) with a balanced calcium/phosphate ratio. 5/6-NX mice on CPD showed increased renal fibrosis and a more pronounced decrease in glomerular filtration rate when compared to 5/6-Nx mice on normal diet (ND). Interestingly, despite comparable levels of serum calcium, phosphate, and parathyroid hormone (PTH), circulating intact fibroblast growth factor-23 (FGF23) was 5 times higher in 5/6-Nx mice on CPD, relative to 5/6-Nx mice on ND. A time course experiment revealed that 5/6-Nx mice on CPD developed progressive renal functional decline, renal fibrosis, cortical bone loss, impaired bone mineralization as well as hypertension, but not left ventricular hypertrophy. Collectively, our data show that the resistance of C57BL/6 mice to 5/6-Nx can be partially overcome by feeding the CPD, and that the CPD induces a profound, PTH-independent increase in FGF23 in 5/6-Nx mice, making it an interesting tool to assess the pathophysiological significance of FGF23 in CKD. | 10.1038/s41598-021-94264-8 |
pubmed_748_7756 | Selective labeling of barstar by the stable (15)N isotope of the valine residue with high selectivity of the label incorporation resulting from the process of gene expression in Escherichia coli BL21(DE3) has been optimized. We have shown that alpha-aminooxyacetic acid (AOAA) significantly reduces the isotope redistribution, thus increasing the selectivity of (15)N incorporation into the synthesized protein, as detected by 2D-NMR. Quantitative measurements were used to determine the selectivity for the incorporation of isotope-labeled valine residue, which was 96% in the case using AOAA. Studies of the dynamics of barstar synthesis showed that no suppression of barstar yield is observed under the regulation of the T7 polymerase expression system by isopropylthio-beta-D-galactoside (IPTG) and rifampicin using AOAA. | 10.1023/b:biry.0000040207.23339.21 |
pubmed_94_1403 | AIMS
The risk of cardiovascular disease is often underestimated in women. This leads to a delay in controlling the risk factors for cardiovascular disease and even delays in prescribing medications with cardiovascular benefit. Our aim was to explore if glucagon-like peptide-1 receptor agonist (GLP-1RA) or sodium-glucose cotransporter-2 inhibitor (SGLT-2i) medications would reduce cardiovascular events in women with type 2 diabetes when atherosclerotic cardiovascular disease (ASCVD) predominates.
MATERIALS AND METHODS
We searched for randomized trials comparing GLP-1RA or SGLT-2i to placebo in people with type 2 diabetes and had a primary outcome exploring major adverse cardiovascular events (MACE). Data concerning women were then extracted. A sensitivity and subgroup analyses were performed according to the class of diabetes medication.
RESULTS
A total of 9 trials (GLP-1RA in 6 trials and SGLT-2i in 3) were included. Of the 84,258 participants enrolled, 30,784 (37%) participants were women. Pooled results showed a statistically significant lower incidence of MACE favouring diabetes medications (GLP-1RA or SGLT-2i) compared to placebo (RR [95%CI]=0.87 [0.80, 0.94]). On restricting the analysis to GLP-1RA then to SGLT-2i, results remained significant with GLP-1RA but not SGLT-2i.
CONCLUSIONS
In women with type 2 diabetes who either have increased cardiovascular risk or established cardiovascular disease and ASCVD predominates, GLP-1RA significantly reduce the incidence of MACE while SGLT-2i result in a non-significant reduction. SGLT-2i may have comparable effect when examined in more studies. GLP-1RA and SGLT-2i should be considered without delay in women with type 2 diabetes and increased risk for cardiovascular disease. | 10.1016/j.diabet.2020.05.002 |
pubmed_877_13944 | Facial mimicry (FM) is an automatic response to imitate the facial expressions of others. However, neural correlates of the phenomenon are as yet not well established. We investigated this issue using simultaneously recorded EMG and BOLD signals during perception of dynamic and static emotional facial expressions of happiness and anger. During display presentations, BOLD signals and zygomaticus major (ZM), corrugator supercilii (CS) and orbicularis oculi (OO) EMG responses were recorded simultaneously from 46 healthy individuals. Subjects reacted spontaneously to happy facial expressions with increased EMG activity in ZM and OO muscles and decreased CS activity, which was interpreted as FM. Facial muscle responses correlated with BOLD activity in regions associated with motor simulation of facial expressions [i.e., inferior frontal gyrus, a classical Mirror Neuron System (MNS)]. Further, we also found correlations for regions associated with emotional processing (i.e., insula, part of the extended MNS). It is concluded that FM involves both motor and emotional brain structures, especially during perception of natural emotional expressions. | 10.3389/fpsyg.2018.00052 |
pubmed_56_16407 | BACKGROUND
Oligometastasis, a recently proposed concept, is defined as an intermediate state of cancer, between localized and systemic disease, that may be well controlled by local ablative treatment. Thymic carcinoma is a rare cancer with a poor prognosis. A definitive management approach has yet to be confirmed by a high level of evidence.
CASE PRESENTATION
We present the case of a 41-year-old female who underwent curative-intent surgery for a stage III squamous cell carcinoma of the thymus. Bone metastases were detected 1 year later by magnetic resonance imaging. These were treated with palliative-intent radiotherapy. Disease progression has not been observed in more than 15 years since the achievement of complete radiological remission.
CONCLUSION
The treatment outcomes in this and other reported cases suggest that some patients with oligometastatic thymic carcinoma may achieve prolonged survival or even cure with low-dose radiotherapy delivered to the metastases. | 10.2147/OTT.S98914 |
pubmed_765_5121 | Objective
The aim was to investigate the effectiveness of pegylated liposomal doxorubicin (PLD), beta-carotene, and a combination of PLD and beta-carotene on JAR and JEG-3 human choriocarcinoma (CC) cell lines for the treatment of CC.
Material and Methods
JAR and JEG-3 cells were cultured. PLD and beta-carotene trial groups were determined with different doses (for single drug trial; PLD 1, 2, 5 μg/mL and beta-carotene 1, 5, 10 μg/mL, and for combined drug trial; all PLD doses combined with beta-carotene 5 μg/mL). Drugs were administered to cultures simultaneously, and 72 hours later the cells were detached using trypsin-ethylenediamine tetraacetic acid solution. The percentage of apoptotic cells was determined by flow cytometry after annexin V staining. One set of the supernatant was collected before trypsin application to investigate beta-human chorionic gonadotropin (β-hCG) and hyperglycosylated hCG (H-hCG) levels. Statistical analyses of the apoptotic ratios were performed using Shapiro-Wilk, Kruskal-Wallis and Mann-Whitney U tests.
Results
Apoptosis increased in JAR and JEG-3 cultures after treatment with all doses of PLD (p<0.05). A single application of each betacarotene dose increased apoptosis in JAR cells (p<0.05) but had no apoptotic effects on JEG-3 cells. In the PLD and beta-carotene combination group, apoptosis increased in both JAR and JEG-3 cells (p<0.05).
Conclusion
To our knowledge, this is the first investigation of the effectiveness of PLD, beta-carotene, and PLD + beta-carotene combination therapy in two different CC cell lines. PLD is a promising chemotherapeutic drug, and beta-carotene can be used as a novel non-chemotherapeutic agent for treatment of CC. Based on the results of this study, vitamin A supplementation may have promise as a preventive measure. However, these data need support from animal experiments and clinical trials. | 10.4274/jtgga.galenos.2020.2019.0199 |
pubmed_968_24064 | Following cervical and uterine cancer, ovarian cancer (OC) has the third rank in gynecologic cancers. It often remains non-diagnosed until it spreads throughout the pelvis and abdomen. Identification of the most effective risk factors can help take prevention measures concerning OC. Therefore, the presented review aims to summarize the available studies on OC risk factors. A comprehensive systematic literature search was performed to identify all published systematic reviews and meta-analysis on associated factors with ovarian cancer. Web of Science, Cochrane Library databases, and Google Scholar were searched up to 17th January 2020. This study was performed according to Smith et al. methodology for conducting a systematic review of systematic reviews. Twenty-eight thousand sixty-two papers were initially retrieved from the electronic databases, among which 20,104 studies were screened. Two hundred seventy-seven articles met our inclusion criteria, 226 of which included in the meta-analysis. Most commonly reported genetic factors were MTHFR C677T (OR=1.077; 95 % CI (1.032, 1.124); P-value<0.001), BSML rs1544410 (OR=1.078; 95 %CI (1.024, 1.153); P-value=0.004), and Fokl rs2228570 (OR=1.123; 95 % CI (1.089, 1.157); P-value<0.001), which were significantly associated with increasing risk of ovarian cancer. Among the other factors, coffee intake (OR=1.106; 95 % CI (1.009, 1.211); P-value=0.030), hormone therapy (RR=1.057; 95 % CI (1.030, 1.400); P-value<0.001), hysterectomy (OR=0.863; 95 % CI (0.745, 0.999); P-value=0.049), and breast feeding (OR=0.719, 95 % CI (0.679, 0.762) and P-value<0.001) were mostly reported in studies. Among nutritional factors, coffee, egg, and fat intake significantly increase the risk of ovarian cancer. Estrogen, estrogen-progesterone, and overall hormone therapies also are related to the higher incidence of ovarian cancer. Some diseases, such as diabetes, endometriosis, and polycystic ovarian syndrome, as well as several genetic polymorphisms, cause a significant increase in ovarian cancer occurrence. Moreover, other factors, for instance, obesity, overweight, smoking, and perineal talc use, significantly increase the risk of ovarian cancer. | 10.1186/s13048-021-00911-z |
pubmed_795_11995 | BACKGROUND
Pseudoaneurysms of the superficial temporal artery have been described following trauma and various surgical procedures. There are no reports in the literature of these lesions following the placement of external ventricular drainage catheters. This article describes two patients and their successful treatment, and reviews diagnostic and treatment strategies.
CASE DESCRIPTION
Two patients developed tender, nonpulsatile masses in the scalp along the former subcutaneous tract of an EVD catheter. Both lesions were successfully excised in the operating room and found to be thrombosed pseudoaneurysms of the superficial temporal artery.
CONCLUSION
Pseudoaneurysms of the parietal branch of the STA may occur secondary to incision of the skin for twist drill hole placement or the use of a sharp trocar for subcutaneous tunneling of catheters. Use of a blunt-tipped trocar may reduce the risk of developing pseudoaneurysms secondary to EVD placement. Knowledge of the possibility of developing these lesions from catheter placement may aid the neurosurgeon in proper diagnosis and treatment. | 10.1016/s0090-3019(02)00796-6 |
pubmed_938_3020 | Reconstructed median sections of staged human embryos were prepared to provide fundamental insight into the developing human brain. 1. At its first appearance as neural plate at stage 8 and even better visible at stages 9 and 10, the rostral end of the CNS is at the chiasmatic plate, that is, at the rostral end of the diencephalon. The telencephalon is a later acquisition. 2. The main parts, already visible in the neural plate, become arranged as neuromeres as the neural tube develops. The neuromeres, defined by definite morphological features, are transversely arranged originally. As morphological entities they are visible longest in the rhombencephalon (up to stages 17-18). 3. The initially uniformly thick walls at stages 12 and 13 develop thickenings: medial and lateral eminences in the forebrain constitute parts of the corpus striatum. The hippocampus forms as a rostrocaudally growing C-shaped thickening in the medial wall of the cerebral hemisphere. The ventricular bulge develops in the alar areas of Rh 1 and the isthmic segment, and develops into the corpus cerebelli. 4. Internal sulci are important landmarks. The sulcus limitans separates alar and basal plates in the rhombencephalon and mesencephalon, but it does not continue into the forebrain. The hypothalamic sulcus separates the hypothalamus from the thalamus (epi-, dorsal, and ventral thalami); the sulcus circularis separates the olfactory bulb from the olfactory tubercle. 5. The embryonic brain develops from approximately day 18 to day 57, i.e., during a period of 5 1/2 weeks. It progresses from a neural plate to a highly complicated, almost spherical organ, parts of which, to judge from their morphology, should be capable of functional competence. | pubmed_938_3020 |
pubmed_314_11186 | PURPOSE
To evaluate the ultrastructural effect of trypan blue 0.1% staining for capsulorhexis on lens epithelial cells (LECs) and capsules.
SETTING
Division of Ophthalmology, University of São Paulo, São Paulo, Brazil.
METHODS
Before capsulorhexis, patients were randomly assigned to 1 of 2 groups. Trypan blue 0.1% staining was performed in the treatment group. No trypan blue was used in the control group. Samples of capsules with LECs were fixed and analyzed with routine optical microscopy techniques, immunohistochemistry for beclin-1 expression (a marker of autophagy), terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling to detect apoptosis, and transmission electron microscopy (TEM). Morphometric analyses were performed, and the 2 sets of data were compared.
RESULTS
Each group comprised 15 patients. Cell death by autophagy and apoptosis was observed in the treatment group but not in the control group. The TEM images of subcapsular epithelium cells showed mitochondrial rupture, dilation of the cisterns of the endoplasmic reticulum, increased cytoplasmic and nuclear electron density, and abnormalities in the nuclear profile of trypan blue-stained cells. Morphometric analysis showed statistically significant differences between the 2 groups in the longest nuclear axes and the ratio between the total nuclear perimeter and the cell area (P = .03). The difference in capsule thickness between groups was not significant.
CONCLUSION
Trypan blue caused LEC death, which supports the hypothesis that staining with trypan blue 0.1% can help reduce the incidence of posterior capsule opacification after cataract surgery.
FINANCIAL DISCLOSURE
No author has a financial or proprietary interest in any material or method mentioned. | 10.1016/j.jcrs.2009.11.005 |
pubmed_124_11662 | Familial dysautonomia, a relatively rare hereditary condition, consists of a baffling array of nervous system malfunctions that seriously disturb the lives of the young victims and their families. Since several of the deficits can be identified as sensory-integrative and as such have been successfully treated in other contexts, it is suggested that sensory integration therapy may benefit these children. Results of a ten-month-old Isralei child appear to support this conjecture and suggest further exploration of the sensory integration approach in evaluation and treatment of dysautonomia and related conditions. | pubmed_124_11662 |
pubmed_708_1569 | The wheat mitochondrial (mt) cox3 has been localized and sequenced. The gene exists as a single copy in the wheat mt master chromosome and is transcribed into a single 1.2 kb RNA, whose extremities have been mapped. Comparison of the wheat and Oenothera cox3 sequences gives ambiguous indications concerning the amino acid coded by the codon CGG. Upstream and downstream of the wheat cox3 gene, two short sequences of 43 bp and 69 bp respectively are present, which are almost identical to sequences present in the flanking regions of other plant mitochondrial genes. These common sequences seem to have played a role in the rearrangements which caused sequence divergence of the plant mt genomes during evolution. Furthermore, mapping of wheat and maize cox3 and cob transcripts suggests that some of these common sequences can play a role in the regulation of transcription or processing. | 10.1007/BF00313247 |
pubmed_308_9519 | The current study investigated the immunomodulatory potential of ethyl acetate soluble supernatant of Lactobacillus casei (LC-EAS) in vitro. The effect of LC-EAS on nitric oxide release was analyzed in RAW 264.7 cells, wherein, an inhibition in nitric oxide production through suppression of inducible nitric oxide synthase mRNA expression was observed. Evaluation of LC-EAS on LPS-induced peripheral blood mononuclear cells showed a down-regulation in TNF-α and IL-6 genes and an upregulation of IL-10. An inhibition in the protein expression of NF-κB, ERK1/2 and STAT3 phosphorylation confirms the immunomodulatory potential of LC-EAS. The effect of LC-EAS on in vitro intestinal epithelial cells was investigated using HT-29 human colon adenocarcinoma cancer cells. LC-EAS exhibited an inhibition of NF-κB and ERK1/2 phosphorylation, whereas STAT3 phosphorylation was unregulated. To evaluate the downstream target of STAT3 upregulation, expression of the intestinal trefoil factor TFF3 which is a NF-κB regulator and STAT3 downstream target was studied. LC-EAS was observed to elevate TFF3 mRNA expression. Overall the study shows that the anti-inflammatory potential of LC-EAS is through inhibition of NF-κB in different cell types. | 10.1007/s12602-012-9122-y |
pubmed_779_15652 | PURPOSE OF REVIEW
Although a patent foramen ovale (PFO) is an established risk factor for cryptogenic ischemic stroke, strategies for secondary prevention remain controversial. Increasing evidence over the past decade from well designed clinical trials supports transcatheter PFO closure for selected patients whose stroke was likely attributable to the PFO. However, patient selection using imaging findings, clinical scoring systems, and in some cases, thrombophilia testing, is crucial for determining patients most likely to benefit from closure, anticoagulation, or antiplatelet therapy.
RECENT FINDINGS
Recent studies have found that patients with a high Risk of Paradoxical Embolism (RoPE) score and those with a thrombophilia benefit more from closure than medical therapy (including antiplatelet or anticoagulant therapy) alone. Meta-analyses have demonstrated an increased short-term risk of atrial fibrillation in closure patients, and that residual shunt after closure predicts stroke recurrence. Last, recent data have been inconclusive as to whether patients receiving medical therapy only benefit more from anticoagulation or antiplatelet therapy, so this remains an area of controversy.
SUMMARY
Transcatheter PFO closure is an evidence-based, guideline-supported therapy for secondary stroke prevention in patients with a PFO and cryptogenic stroke. However, proper patient selection is critical to achieve benefit, and recent studies have helped clarify those patients most likely to benefit from closure. | 10.1097/MOH.0000000000000672 |
pubmed_293_4071 | Many epidemiological studies find that people exposed to aircraft, road or railway traffic noise are at increased risk of illness, including cardiovascular disease (CVD) and depression. It is unclear how the combined exposure to these different types of traffic noise affects disease risks. This study addresses this question with a large secondary data-based case-control study ("NORAH disease risk study"). The Akaike information criterion (AIC) is used to compare two different models estimating the disease risks of combined traffic noise. In comparison with the conventional energetic addition of noise levels, the multiplication of CVD risks as well as depression risks reveals a considerably better model fit as expressed by much lower AIC values. This is also the case when risk differences between different types of traffic noise are taken into account by applying supplements or reductions to the single traffic noise pressure levels in order to identify the best fitting energetic addition model. As a consequence, the conventionally performed energetic addition of noise levels might considerably underestimate the health risks of combined traffic noise. Based on the NORAH disease risk study, "epidemiological risk multiplication" seems to provide a better estimate of the health risks of combined traffic noise exposures compared to energetic addition. If confirmed in further studies, these results should imply consequences for noise protection measures as well as for traffic planning. | 10.3390/ijerph16091665 |
pubmed_1070_9853 | The aim of this work was to evaluate the performance of the fungus Lentinula edodes UEC 2019 in the treatment of an effluent derived from a wood laminate manufacturing process. The factorial design methodology was employed to verify the influence of the source of nitrogen, co-substratum and treatment time variables on the color and total phenols reduction. Assays were conducted in Erlenmeyer flasks and bench bioreactor and the obtained results showed that the best conditions for the effluent remediation were observed when using the effluent itself as the nitrogen source (1g/L) and glucose (79 g/L) as co-substratum (glucose) during a treatment period of 30 days. It was possible the remove 92% phenol, 97% color and reduce the COD in the bioreactor by 99% while controlling the temperature, pH and feeding. These results demonstrate that the fungus was able to use the effluent components as substrate and that it has potential for use in wood lamination effluent remediation. | 10.1016/j.jhazmat.2008.08.044 |
pubmed_465_5029 | The abilities of various agonistic and antagonistic analogs of GnRH to modulate ovarian estrogen production were compared with their relative potencies to regulate pituitary LH release. Granulosa cells from immature hypophysectomized rats were cultured for 2 days in the presence of FSH and aromatase substrate (delta 4-androstenedione), with or without various concentrations of GnRH agonists or 10(-8) M GnRH plus various concentrations of selected GnRH antagonists. FSH treatment increased estrogen production, whereas concomitant treatment with various GnRH agonists resulted in dose-dependent decreases in estrogen production. des-Gly10-[D-Ser(TBu)6] Pro9-NHEt-GnRH proved most potent at both the ovarian and pituitary levels, being 170- and 190-fold greater than those values for the GnRH decapeptide, respectively. In general, the ovarian and pituitary potencies of all 10 agonists studied were comparable, with a correlation coefficient of 0.98. When added together with 10(-8) M GnRH, the GnRH antagonists caused dose-dependent blockage of the inhibitory effect of GnRH. Among 7 antagonists tested, [Ac-D-Phe1,D-p-cl-Phe2,D-TYrp3,6]GnRH was shown to be most potent at the pituitary level (half maximal inhibitory dose ratio: IDR50 antagonist/GnRH = 0.17) and blocked the GnRH inhibition at the ovarian level with an IDR50 value of 4.4. The potencies of the antagonists to block the GnRH effect at the pituitary and ovarian levels were comparable, yielding a correlation coefficient of 0.97. Although one cannot rule out subtle differences in the specificities of the respective GnRH target tissues due to minor disparities between pituitary and ovarian potencies of some analogs, the present results demonstrate an overall agreement of responsiveness between ovarian granulosa cells and pituitary gonadotrophs to GnRH agonists and antagonists. | 10.1210/endo-112-2-689 |
pubmed_974_15578 | Previous studies have demonstrated that sirolimus has therapeutic effects for Alzheimer's disease which characterized by cognitive dysfunction. However, its underlying mechanisms have not been fully elucidated. In the present study, we aimed to investigate the mechanisms of therapeutic effects of sirolimus for cognitive dysfunction rat model which induced by chronic administration of scopolamine. Forty Wistar rats were randomly divided into 4 groups (n=10 each): saline group and scopolamine group, sirolimus plus scopolamine group and 3-methyladenine pretreatment group. Morris water maze test was applied to measure the cognitive function of rat. After behavioral test, rats were sacrificed and prefrontal cortex and hippocampus were harvested for measuring amyloid-β (Aβ), Beclin-1 and mammalian target of rapamycin (mTOR). Compared with saline group, scopolamine administered significantly decreased the cognitive performance of rats during the Morris water maze test and changed Aβ, Beclin-1 and mTOR levels in rat prefrontal cortex and hippocampus (P<0.05); In addition, rats in sirolimus plus scopolamine group significantly reversed scopolamine-induced effects (P<0.05). Most importantly, 3-methyladenine abrogated the effects of sirolimus on scopolamine-induced cognitive dysfunction (P<0.05). In conclusion, the mechanism of sirolimus exerting therapeutic effects for scopolamine-induced cognitive dysfunction is likely related to the activation of autophagy. | pubmed_974_15578 |
pubmed_572_12114 | CONTEXT
Physician empathy influences rapport with patients and improves outcomes, but it is not well understood as an outcome of osteopathic medical education.
OBJECTIVE
To determine how clerkship preceptors at Touro University College of Osteopathic Medicine-CA (TUCOM) in Vallejo define empathy and how they compare observed empathetic behavior of TUCOM students with that of other medical students.
METHODS
Cross-sectional data were obtained from a survey of TUCOM clinical preceptors comparing TUCOM students with other medical students on 10 behaviors. Results were analyzed with a 2-tailed z test of proportional difference at the 95% confidence level.
RESULTS
Of 650 preceptors contacted, 177 responded and were included in the final analysis (27%). Survey item reliability was high (Cronbach α=0.96). A majority of preceptors (59% to 71%) considered TUCOM students "similar" to other medical students for each behavior. A majority of preceptors (107 [60%]) shared a definition of empathy with one another and with the National Board of Osteopathic Medical Examiners and the American Association of Colleges of Osteopathic Medicine. Approximately 39% of preceptors rated TUCOM students "better" or "advanced" for "displays of empathy" compared with approximately 30% of preceptors who rated students as better or advanced across all 10 behaviors. Preceptors who shared a definition of empathy rated TUCOM students as better or advanced at a significantly higher rate for "displays of empathy" (z=1.982, P<.05) compared with preceptors who did not share a definition (n=70). Osteopathic preceptors (n=67) rated TUCOM students significantly higher on "displays of empathy" (z=2.82, P<.05) and "clear and effective communication to patients, families and co-workers" (z=2.83, P<.01) than did allopathic preceptors. No significant differences were found based on number of years as a preceptor or on the combination of types of students the preceptor taught.
CONCLUSION
Most clinical preceptors shared a definition of empathy, and they were able to observe and rate displays of it in clerkship students. Preceptors rated TUCOM students more favorably than other students they taught for displays of empathy. | 10.7556/jaoa.2017.100 |
pubmed_256_3739 | Hemizygous and homozygous deletions of the type I interferon gene cluster (IFN) have been detected in about 20% of acute lymphoblastic leukemias. A putative tumor suppressor gene (TSG) is thought to be located centromeric to the IFN cluster on chromosomal bands 9p21-22. We studied the accuracy of fluorescence in situ hybridization (FISH) for detecting deletions in interphase cells using yeast artificial chromosome (YAC) clones containing all or part of the IFN cluster. FISH probes were generated from YACs (320-1300 kb in size) by a sequence-independent amplification technique (SIA). Fifteen cell lines (nine T-ALL, three B-cell precursor ALL, one B-ALL, one AML, one CML-BC) that had been well characterized by conventional cytogenetic analysis and molecular techniques were analyzed. We were able to detect all numerical changes of the IFN cluster including homozygous and hemizygous deletions accurately and to define subclones of the cell lines. Moreover, in six cell lines we were able to identify subclones. In dilution experiments the detection thresholds for subpopulations with homozygous and hemizygous deletions were determined to be 5% and 7.5%, respectively. | 10.1016/s0165-4608(95)00026-7 |
pubmed_35_23499 | BACKGROUND
To evaluate the patterns of treatment failure in patients with stage IIB cervical carcinoma with high-risk factors following radiotherapy given concurrently with combination chemotherapy.
METHODS
A retrospective analysis of 349 patients with stage IIB cervical carcinoma with high-risk factors (lesion size >/= 4 cm, lymph node metastasis, high-risk cell type) treated by radiotherapy and cisplatin-based chemotherapy was performed. Sites of treatment failure were categorized as pelvic, pelvic plus distant metastases, and distant metastases alone. Pelvic failure included local and pelvic nodal failures.
RESULTS
Of the 349 patients, treatment failure occurred in 79 patients (22.6%). Forty-six (13.2%) had persistent disease and 33 (9.5%) had recurrent disease. Among these 79 patients, overall pelvic failure was observed in 67%, of whom 72% had local failure; 19%, pelvic nodal failure; and 9%, local with pelvic nodal failure. Incidences of distant metastases alone and pelvic with distant metastases were 24% and 9%. In the 26 patients with distant metastases either alone or combined with pelvic failure, the most frequent metastatic region was the paraaortic lymph node (50%). The distant metastasis rate was 6.5% (19/289) in the pelvic tumor control group and 11.6% (7/60) in the pelvic failure group. Pelvic failure was the most frequent failure in the group with tumor size of 4 cm or more, whereas, for the positive-lymph-node group, distant metastasis was most frequent and metastases to paraaortic lymph nodes were common. The incidences of pelvic failure alone and distant metastases were similar in the high-risk cell-type group, and the distant metastasis regions were mostly paraaortic lymph nodes.
CONCLUSION
Although systemic chemotherapy was administered concurrently with radiotherapy, the incidence of pelvic failure was highest, followed by paraaortic lymph node metastases, in patients with stage IIB cervical carcinoma with high-risk factors, following radiotherapy with combination chemotherapy. To evaluate the patterns of treatment failure in patients with stage IIB cervical carcinoma with high-risk factors following radiotherapy given concurrently with combination chemotherapy. | 10.1007/s10147-003-0378-9 |
pubmed_1092_25441 | Radiation-induced autophagy is believed to represent a radioprotective mechanism of cancer cells. Thus, its inhibition should support radiation treatment and increase its efficacy. On the other hand, there is evidence that radiation alone or in combination with various chemical agents can induce autophagy that results into increased cell death, especially within transformed apoptosis-resistant cells. In this paper, besides description of autophagic process and its relation to cancer and radiotherapy, we compared two contradictory radiosensitization approaches that employ inhibition and induction of autophagy. In spite of the classical concept based on cytoprotective model, there is a plethora of recently developed inducers of autophagy, which indicates the future trend in radiosensitization via modulation of autophagy. Because contemporary literature is conflicting and inconsistent in this respect, we reviewed the recent studies focused on enhancement of sensitivity of cancer cells toward radiation in regard to autophagy, revealing some striking discrepancies. The deeper the knowledge, the more complex this situation is. To interpret results of various studies correctly one has to take into account the methodology of autophagy assessment and also the fact that radiosensitization might be mediated by other than intrinsic mechanisms related to autophagy. Notwithstanding, targeting autophagy remains an attractive anti-tumor strategy. | pubmed_1092_25441 |
pubmed_269_16639 | Acute intermittent porphyria (AIP) is an autosomal dominant disease caused by the hepatic deficiency of porphobilinogen deaminase (PBGD) and the slowdown of heme biosynthesis. AIP symptomatology includes life-threatening, acute neurovisceral or neuropsychiatric attacks manifesting in response to precipitating factors. The latter promote the upregulation of 5-aminolevulinic acid synthase-1 (ALAS1), the first enzyme of heme biosynthesis, which promotes the overload of neurotoxic porphyrin precursors. Hemin or glucose infusions are the first-line therapies for the reduction of ALAS1 levels in patients with mild to severe AIP, while liver transplantation is the only curative treatment for refractory patients. Recently, the RNA-interference against ALAS1 was approved as a treatment for adult and adolescent patients with AIP. These emerging therapies aim to substitute dysfunctional PBGD with adeno-associated vectors for genome editing, human PBGD mRNA encapsulated in lipid nanoparticles, or PBGD protein linked to apolipoprotein A1. Finally, the impairment of glucose metabolism linked to insulin resistance, and mitochondrial aberrations during AIP pathophysiology provided new therapeutic targets. Therefore, the use of liver-targeted insulin and insulin-mimetics such as α-lipoic acid may be useful for overcoming metabolic dysfunction in these subjects. Herein, the present review aims to provide an overview of AIP pathophysiology and management, focusing on conventional and recent therapeutical approaches. | 10.3390/biomedicines10030648 |
pubmed_702_5566 | OBJECTIVE
The purpose of this study was to assess the use-effectiveness of oral contraceptives (OCs) in Europe according to body mass index (BMI), weight, age, and other factors.
STUDY DESIGN
In a planned secondary analysis, we used data from the European Active Surveillance Study on Oral Contraceptives, which was a prospective active cohort surveillance study of 59,510 OC users, to assess the effectiveness of OCs overall and by BMI, weight, age, duration of use, ethinylestradiol dose, regimen type, starting/switching status, and parity. Self-reported unplanned pregnancies during OC use were confirmed by interview.
RESULTS
An analysis of OC effectiveness (112,659 women-years of exposure and 545 unplanned pregnancies) found little variation in effectiveness by BMI/weight. Failure rates decreased after 30 years of age and with an increasing duration of use.
CONCLUSION
OC users in Europe reported high contraceptive effectiveness with "typical use." Failure rates decreased with age and duration of use. BMI and weight had little, if any, influence on effectiveness. | 10.1016/j.ajog.2009.03.017 |
pubmed_723_20901 | ETHNOPHARMALOGICAL RELEVANCE
Blood purification practices, also referred to as blood cleansing or detoxification, is an ancient concept which is widespread amongst African traditional medicine, but for which no modern scientific basis exists. There prevails considerable ambiguity in defining what a blood purifier is.
AIM OF THE STUDY
The purpose of this review is to firstly define what a blood purifier is in the context of African traditional medicine and compare to other cultural and westernized interpretations. Thereafter, this study identifies traditionally used medicinal plants used as blood purifiers in southern Africa and correlates these species to scientific studies, which may support evidence for these "blood purifying plant species".
MATERIALS AND METHODS
Ethnobotanical books and review articles were used to identify medicinal plants used for blood purification. Databases such as Scopus, ScienceDirect, PubMed and Google Scholar were used to source scientific articles. An evaluation was made to try correlate traditional use to scientific value of the plant species.
RESULTS
One hundred and fifty nine plant species have been documented as traditional remedies for blood purification. Most of the plant species have some pharmacological activity, however, very little link to the traditional use for blood purification. There has been some justification of the link between blood purification and the use as an antimicrobial and this has been explored in many of the plant species identified as blood purifiers. Other pharmacological studies specifically pertaining to the blood require further attention.
CONCLUSION
Irrespective of the ambiguity of interpretation, medicinal plants used to "cleanse the blood", play an important holistic role in traditional medicine and this review with recommendations for further study provides some value of exploring this theme in the future. | 10.1016/j.jep.2019.112434 |
pubmed_139_13314 | The effect of interleukin-2 (IL-2) preparations on the susceptibility of YAC cells to mouse natural killer (NK) cells was examined. Crude IL-2 preparations induced a significant decrease in the susceptibility of YAC cells. Highly purified IL-2 preparations, however, did not have a similar effect. Since the IL-2 preparations used in this study were purified from the culture supernatant of Con A activated spleen cells (Con A Sup.), our results indicated the presence in Con A Sup. of a lysis resistance inducing factor (LRIF), distinct from IL-2. We were able to purify LRIF from Con A Sup. by preparative isoelectric focusing and determined its isoelectric pH to be 4.8. | 10.1016/0165-2478(87)90039-3 |
pubmed_506_11427 | Lakes are a major component of boreal landscapes, and whereas lake CO2 emissions are recognized as a major component of regional C budgets, there is still much uncertainty associated to lake CH4 fluxes. Here, we present a large-scale study of the magnitude and regulation of boreal lake summer diffusive CH4 fluxes, and their contribution to total lake carbon (C) emissions, based on in situ measurements of concentration and fluxes of CH4 and CO2 in 224 lakes across a wide range of lake type and environmental gradients in Québec. The diffusive CH4 flux was highly variable (mean 11.6 ± 26.4 SD mg m(-2) d(-1) ), and it was positively correlated with temperature and lake nutrient status, and negatively correlated with lake area and colored dissolved organic matter (CDOM). The relationship between CH4 and CO2 concentrations fluxes was weak, suggesting major differences in their respective sources and/or regulation. For example, increasing water temperature leads to higher CH4 flux but does not significantly affect CO2 flux, whereas increasing CDOM concentration leads to higher CO2 flux but lower CH4 flux. CH4 contributed to 8 ± 23% to the total lake C emissions (CH4 + CO2 ), but 18 ± 25% to the total flux in terms of atmospheric warming potential, expressed as CO2 -equivalents. The incorporation of ebullition and plant-mediated CH4 fluxes would further increase the importance of lake CH4 . The average Q10 of CH4 flux was 3.7, once other covarying factors were accounted for, but this apparent Q10 varied with lake morphometry and was higher for shallow lakes. We conclude that global climate change and the resulting shifts in temperature will strongly influence lake CH4 fluxes across the boreal biome, but these climate effects may be altered by regional patterns in lake morphometry, nutrient status, and browning. | 10.1111/gcb.12741 |
pubmed_495_14477 | This study of thyroid histopathological data from hospitals in the South West Thames region was undertaken to assess current practice and the scope for improvement. Over a 6 month period, 186 thyroid operations were performed on 179 patients at eight hospitals serving almost 1.7 million people. The frequency of thyroidectomy in different hospitals varied from 13 to 35 per 100,000 per year and 6.4% of the operations were second thyroidectomies. Benign multinodular goitre was the most common histological finding (34%). A benign solitary nodule was found in 36% and malignancy in 8.4% of the specimens. Correlation of histological analysis and type of operation suggested that a variety of operations were performed for the same pathological condition and that some operations were diagnostic procedures only. Overall, 63 of the 186 operations (34%) might have been avoided by a firm preoperative diagnosis. Only 67 thyroid fine needle aspiration biopsies (FNAC) were performed at the eight hospitals during the study period. Only 15 (8%) of the patients who underwent thyroid operation had been investigated by FNAC. Reduction in thyroid surgery through more widespread use of FNAC could result in savings of 100,000 pounds per million population per year. Regional activity data show that more than 50 surgeons currently undertake a workload of less than 500 thyroidectomies each year. Increased subspecialisation may be required to reduce costs and raise standards. | pubmed_495_14477 |
pubmed_1011_2097 | A quantitiative electroimmunodiffusion (EID) assay was developed for apolipoprotein B (apoB), the major apoprotein of human plasma low density lipoproteins (LDL) and very low density lipoproteins (VLDL). Specificity, sensitivity (30-200 ng) and reproducibility (11%) were established. We used this system to determine the amount of buffer-soluble apoB in supernatant fractions from homogenates of the intima from grossly normal human aortas. Assays of whole tissue minces yielded only one-third of the apoB in supernatant fractions. Intimal homogenates contained 0.34-18.45 mug of apoB/mg of tissue, dry weight (mean 5.42 +/- 3.95 SD). We also found that no apoB was detected in the homogenates of adjacent tunica media. Furthermore, most of the intimal apoB was found in the LDL density (d) fraction (d 1.006-1.063) after differential ultracentrifugation, while the VLDL (d less than 1.006) fraction contained only negligible amounts of apoB. By electron microscopy, it was determined that the LDL density fraction contained particles 200-250 A in diameter which were similar in size to plasma LDL. These results suggest that grossly normal aortas contain significant quantities of intact LDL. | 10.1161/01.res.40.1.56 |
pubmed_587_9583 | The response to the HIV/AIDS pandemic in Africa has so far ignored important traditional African values and attitudes toward disease and commerce. These values and attitudes are significantly different from the libertarian, market-driven, profit-oriented values and practices of important sectors of the Western world. To deal with this epidemic, the world should consider respect for, and possibly even adoption of those African values, which provide for people in genuine need, irrespective of their ability to pay. HIV/AIDS vaccine research indigenous to Africa is also not always taken seriously, and struggles to find adequate funding for such research within or outside of the continent have been extremely difficult. A better appreciation of knowledge systems and values indigenous to the African experience is important in the fight against the HIV/AIDS pandemic. | 10.1076/jmep.27.2.217.2988 |
pubmed_1034_20438 | Fluorogenic probes targeting G-quadruplex structures have emerged as the promising toolkit for functional research of G-quadruplex and biosensor development. However, their biosensing applications are still largely limited in in-tube detection. Herein, we proposed a fluorescent bioimaging method based on enzyme-generated G-quadruplexes for detecting apoptotic cells at the cell and tissue level, namely, terminal deoxynucleotidyl transferase (TdT)-activated de novo G-quadruplex synthesis (TAGS) assay. The detection target is genomic DNA fragmentation, a biochemical hallmark of apoptosis. The TAGS assay can efficiently "tag" DNA fragments via using their DNA double-strand breaks (DSBs) to initiate the de novo synthesis of G-quadruplexes by TdT with an unmodified G-rich dNTP pool, followed by a rapid fluorescent readout upon the binding of thioflavin T (ThT), a fluorogenic dye highly specific for G-quadruplex. The feasibility of the TAGS assay was proved by in situ sensitive detection of individual apoptotic cells in both cultured cells and tissue sections. The TAGS assay has notable advantages, including being label-free and having quick detection, high sensitivity and contrast, mix-and-read operation without tedious washing, and low cost. This method not only shows the feasibility of G-quadruplex in tissue bioanalysis but also provides a promising tool for basic research of apoptosis and drug evaluation for antitumor therapy. | 10.1021/acs.analchem.6b04360 |
pubmed_910_19438 | The ability to generate a high racket speed and a large amount of racket kinetic energy on impact is important for table tennis players. The purpose of this study was to understand how mechanical energy is generated and transferred in the racket arm during table tennis backhands. Ten male advanced right-handed table tennis players hit topspin backhands against pre-impact topspin and backspin balls. The joint kinetics at the shoulder, elbow and wrist of the racket arm was determined using inverse dynamics. A majority of the mechanical energy of the racket arm acquired during forward swing (65 and 77% against topspin and backspin, respectively) was due to energy transfer from the trunk. Energy transfer by the shoulder joint force in the vertical direction was the largest contributor to the mechanical energy of the racket arm against both spins and was greater against backspin than against topspin (34 and 28%, respectively). The shoulder joint force directed to the right, which peaked just before impact, transferred additional energy to the racket. Our results suggest that the upward thrust of the shoulder and the late timing of the axial rotation of the upper trunk are important for an effective topspin backhand. | 10.1080/14763141.2016.1159722 |
pubmed_240_8567 | The relationship between nurses, doctors and patients is not equal in terms of power. The nurse or doctor has a body of knowledge that the patient does not. The patient may be feeling ill and nervous, perhaps fearing a bad diagnosis. The nurse or doctor is nearly always the most powerful person in the care equation. The playing field in health is not a level one. | 10.12968/bjon.2012.21.17.1042 |
pubmed_465_9617 | Postoperative immunochemotherapy with mitomycin C (MMC), 5-fluorouracil (5-FU) and OK-432 was evaluated as adjuvant therapy for curative resection in the cases of gastric cancer. One hundred and twenty-two patients (28 were excluded) were randomly assigned to 3 groups: Group A-MMC and 5-FU (28 cases); Group B-MMC, 5-FU and OK-432 (33 cases); Group C-control (33 cases). There were no differences in the back ground factors influencing survival time among each group. Group B showed better results in survival rate and disease free interval as compared with Group A or C. Minor and reversible side effects such as enterogastric disorder, leukopenia (less than 3000/mm3), thrombo cytopenia (less than 7 X 10(4)/mm3) and elevation of serum transaminase (S-GPT greater than or equal to 100 unit) were equivalently observed in frequency in each Group A and B, but they were milder in Group B than Group A. | pubmed_465_9617 |
pubmed_26_11361 | Environmental factors have long been thought to have a role in the etiology of idiopathic Parkinson's disease (PD). Since the discovery of the selective neurotoxicity of MPTP to dopamine cells, suspicion has focused on paraquat, a common herbicide with chemical structure similar to 1-methyl-4-phenylpyridinium (MPP+), the MPTP metabolite responsible for its neurotoxicity. Although in vitro evidence for paraquat neurotoxicity to dopamine cells is well established, its in vivo effects have been ambiguous because paraquat is di-cationic in plasma, which raises questions about its ability to cross the blood brain barrier. This study assessed the brain uptake of [(11)C]-paraquat in adult male rhesus macaques using quantitative PET imaging. Results showed minimal uptake of [(11)C]-paraquat in the macaque brain. The highest concentrations of paraquat were seen in the pineal gland and the lateral ventricles. Global brain concentrations including those in known dopamine areas were consistent with the blood volume in those structures. This acute exposure study found that paraquat is excluded from the brain by the blood brain barrier and thus does not readily support the causative role of paraquat exposure in idiopathic Parkinson's disease. | 10.1016/j.brainres.2008.12.033 |
pubmed_411_14847 | Based on Surveillance, Epidemiology, and End Results studies, most renal cancers are low grade and slow growing. Long-term, single-center studies show excellent outcomes for T1a renal cell carcinoma (RCC), comparable to partial nephrectomy without affecting renal function and with much lower rates of complications. However, there are no multicenter randomized controlled trials of multiple ablative modalities or comparison with partial nephrectomy, and most studies are single-arm observational studies with short-term and intermediate follow-up. For treatment of stage T1a RCC, percutaneous TA is an effective alternative to surgery with preservation of renal function, low risk, and comparable overall and disease-specific survival. | 10.1016/j.rcl.2020.06.004 |
pubmed_558_21476 | The objective of the study was to evaluate the feasibility of a UK-based real-time service to improve the diagnosis and management of lymphoproliferative disorders (LPDs) in Ghana. Adult patients reporting to hospital with a suspected LPD, during a 1 year period, were prospectively enrolled. Bone marrow and/or lymph node biopsies were posted to the Haematology Malignancy Diagnostic Service (HMDS), Leeds, UK and underwent morphological analysis and immunophenotyping. Results were returned by e-mail. The initial diagnoses made in Ghana were compared with the final HMDS diagnoses to assess the contribution of the HMDS diagnosis to management decisions. The study was conducted at the two teaching hospitals in Ghana-Komfo Anokye, Kumasi and Korle Bu, Accra. Participants comprised 150 adult patients (>/=12 years old), 79 women, median age 46 years. Bone marrow and lymph node biopsy samples from all adults presenting with features suggestive of a LPD, at the two teaching hospitals in Ghana, over 1 year were posted to a UK LPD diagnostic centre, where immunophenotyping was performed by immunohistochemistry. Molecular analysis was performed where indicated. Diagnostic classifications were made according to international criteria. Final diagnosis was compared to the initial Ghanaian diagnosis to evaluate discrepancies; implications for alterations in treatment decisions were evaluated. Median time between taking samples and receiving e-mail results in Ghana was 15 days. Concordance between initial and final diagnoses was 32% (48 of 150). The HMDS diagnosis would have changed management in 31% (46 of 150) of patients. It is feasible to provide a UK-based service for LPD diagnosis in Africa using postal services and e-mail. This study confirmed findings from wealthy countries that a specialised haematopathology service can improve LPD diagnosis. This model of Ghana-UK collaboration provides a platform on which to build local capacity to operate an international quality diagnostic service for LPDs. | 10.1007/s12308-009-0032-1 |
pubmed_1025_3020 | The helical shape of the thin filaments causes their passive counterclockwise rotation during muscle stretch that increases tensile stress and torque at first by unwinding and then by winding up the four anchoring Z-filaments. This means storage of energy in the series elastic Z-filaments and a considerable decrease of the liberated energy of heat and work to (h-w(ap)), where h is the heat energy and w(ap) the stretch energy induced from outside by an apparatus. The steep thin filament helix with an inclination angle of 70° promotes the passive rotation during stretch, but impedes the smooth sliding of shortening by increased friction and production of frictional heat. The frictional heat may be produced by the contact with the myosin cross-bridges: (1) when they passively snap on drilling thin filaments from cleft to cleft over a distance 2 × 2.7 nm = 5.4 nm between the globular actin monomers in one groove, causing stepwise motion; or (2) when they passively cycle from one helical groove to the next (distance 36 nm). The latter causes more heat and may take place on rotating thin filaments without an effective forward drilling ("idle rotation"), e.g., when they produce "unexplained heat" at the beginning of an isometric tetanus. In an Appendix to this paper the different states of muscle are defined. The function of its most important components is described and rotation model and power-stroke model of muscular contraction is compared. | 10.3390/ijms12052891 |
pubmed_585_5719 | Dienogest (DNG) is a 19-nortestosterone derivative (a C-19 progestogen) with a cyanomethyl instead of an ethinyl group at the C-17 position, which may make the compound elicit fewer hepatic effects than other C-19 nortestosterone derivatives. Its similarity to norethisterone is reflected in its high endometrial efficacy, which could explain the high stability of the menstrual cycle women achieve when they use DNG in combination with ethinyl estradiol (EE) or with estradiol valerate (E2V). Its strong endometrial efficacy underlies the use of DNG (on its own) to treat endometriosis, and gives it antiproliferative and anti-inflammatory effects in the treatment of endometriotic lesions. Properties derived from its C-19 derivative structure include its short plasma half-life, of about 10h (which means the drug is not accumulated), and its high oral bioavailability, of more than 90%. However, DNG also has some of the properties of typical of progesterone derivatives, including a lack of effect on the metabolic and cardiovascular systems, and considerable antiandrogenic activity, the latter increased by its lack of affinity to the sex-hormone binding globulin (SHBG), in contrast to other C-19 progestogens. DNG has no glucocorticoid and no antimineralocorticoid activity. It also has no antiestrogenic activity, which suggests that it should not antagonize estradiol's beneficial effects. This is important for its use in the treatment of endometriosis, because, due to DNG's low gonadotropic activity, E2 levels are not decreased to zero, in contrast to treatments with gonadotropin-releasing hormone (GnRH) analogues. This maintenance beneficial E2 effects is of particular importance for the general tolerability of the first contraceptive pill to use E2V instead of EE, although clinical endpoint studies are still ongoing. These studies are expected, on the basis of its pharmacology, to demonstrate the cardiovascular safety of the new pill. | 10.1016/j.maturitas.2012.01.018 |
pubmed_810_5715 | The advent of the Internet is among the most significant changes in recent decades and has greatly affected the entire range of human experience. However, it has, in turn, led to the emergence of psychopathological features of addiction linked to its use. Literature on the clinical management of the distress related to Internet use systematically measures up to an evolving nosography, with ambiguous definitions of the phenomenon and a diversity of diagnostic, prognostic, and therapeutic criteria. To date, case studies on "Internet addiction" treatment are rather limited, and no standard clinical treatment protocols exist. With regard to pharmacological treatment options, empirical or anecdotal assessments are mostly referred to. The aim of this article was to review current literature on Internet addiction treatment and assess the extent to which specific pharmacological interventions alleviate these patients' symptomatic burden, to propose a rationale that may guide the therapeutic approach. To this end, we also explored pharmacological interventions that target patterns of comorbidity and underlying psychopathological dimensions shared with other behavioral or substance addictions. | 10.1097/WNF.0b013e31827172e5 |
pubmed_856_15324 | Lesbian, gay, bisexual, transgender, queer, and other sexual and gender (LGBTQ+) minorities experience intimate partner violence (IPV) at higher rates than heterosexual and/or cisgender people. Providers often are less prepared to work with LGBTQ+ survivors, which can be the result of a reliance on stereotypes on what constitutes an IPV victim. This article provides recommendations for working with LGBTQ+ survivors, including screening for IPV regardless of sexual orientation or gender identity, participating in LGBTQ+-affirming trainings regarding IPV, and creating a welcoming and inclusive space that promotes LGBTQ+ survivors' comfort in disclosing IPV. | 10.1016/j.pop.2021.02.006 |
pubmed_779_10784 | This study aimed to examine the factors associated with willingness to complete advance directives (ADs) in community-dwelling older adults. In total, 121 community-dwelling older adults in Korea completed the questionnaires inquiring about their willingness and perceptions in completing ADs (susceptibility, severity, benefits, barriers, and cues to action), which were based on the Health Belief Model. The mean score for willingness to complete ADs was 6.2 (SD = 3.6). A multiple linear regression analysis showed that higher scores of perceived severity (β = 0.199, p = 0.021), perceived benefits (β = 0.221, p = 0.016), and cues to action (β = 0.159, p = 0.030) were associated with a greater willingness to complete ADs. However, higher scores of perceived barriers (β = -0.409, p < 0.001) were likely to lower the willingness to complete ADs. This study highlights that future interventions aimed at increasing AD completion rates in older adults should consider improving perceived severity, benefits, and cues to action and minimizing perceived barriers. | 10.1016/j.gerinurse.2021.05.006 |
pubmed_191_18114 | Myc is a key regulator of cell growth, differentiation and apoptosis, and affects cell fate decisions by activating as well as by inhibiting the expression of cellular genes. Myc is a member of the basic region-helix-loop-helix-leucine zipper (b-HLH-Zip) class of transcription factors, which heterodimerizes with the Max protein and recognizes a consensus Myc binding motif. Stimulation of gene expression by Myc is thought to be mediated by direct binding of Myc-Max heterodimers to specific target genes. So far, only a few genes have been identified as direct binding targets of Myc, raising the possibility that Myc affects gene expression also by indirect mechanisms. In this work we present evidence that v-Myc encoded by the avian retrovirus MC29 stimulates activating transcription factor 2 (ATF2)-dependent transcription. Analysis of the effect of Myc on ATF2 shows that v-Myc prolongs the half-life of ATF2 and induces the phosphorylation of N-terminal sites of ATF2 (Thr-69 and Thr-71) which have previously been identified as the target sites of stress-activated protein kinases and implicated in the regulation of ATF2 activity. Taken together, our results suggest that v-Myc can affect gene expression indirectly by modulating the activity of ATF2. | 10.1038/sj.onc.1204966 |
pubmed_288_7589 | The calcitonin receptor-like receptor (crlr) is a major endothelial cell receptor for adrenomedullin, a peptide vasodilator involved in cardiovascular development, homeostasis, and disease. Here, we used the zebrafish (Danio rerio) model to characterize the role of crlr in vascular development. Crlr is expressed within somites from the 4- to the 13-somite stage and by arterial progenitors and axial vessels during zebrafish development. Loss of crlr results in profound alterations in vascular development and angiogenesis, including atrophic trunk dorsal aorta and interruption of anterior aortic bifurcation, delay in intersomitic vessel development, and lack of blood circulation. Remarkably, crlr morphants are characterized by the loss of arterial endothelial cell identity in dorsal aorta, as shown by the lack of expression of the arterial markers ephrin-B2a, DeltaC, and notch5. Down-regulation of crlr affects vascular endothelial growth factor (vegf) expression, whereas vegf overexpression is sufficient to rescue arterial differentiation in crlr morphants. Finally, genetic and biochemical evidences indicate that somitic crlr expression is under the control of sonic hedgehog. These data demonstrate that crlr plays a nonredundant role in arterial differentiation, representing a novel element of the sonic hedgehog-vegf-notch signaling cascade that controls arterial/venous fate. | 10.1182/blood-2007-10-118166 |
pubmed_521_4158 | Interest has increased considerably in the past few years in the possible interactions amongst insulin, plasma lipoproteins and several components of the haemostatic system. There is now consistent epidemiological, clinical and experimental evidence that hypertriglyceridaemia, in particular, may represent a procoagulant state involving derangements of both blood coagulation and fibrinolysis. Imbalance in the haemostatic system secondary to increased clotting activity, impaired fibrinolytic function, or a combination thereof, should influence the growth and final size of evolving thrombi and predispose to arterial occlusion. This might be of particular significance in the coronary circulation, where a hypercoagulable state is likely to promote thrombosis at the site of a suddenly ruptured atherosclerotic plaque. In addition, there is accumulating experimental evidence that the haemostatic system plays a part in plaque formation and plaque growth. Basic research on the link between haemostasis and atherosclerosis should be given high priority, because modulation of haemostatic function will probably be a potent complementary approach to the prevention of coronary heart disease. | pubmed_521_4158 |
pubmed_434_10610 | Every year, hundreds of transgendered people from the United States, Europe, Asia, Canada, and Australia travel to Thailand to undergo cosmetic and gender reassignment surgeries (GRS). Many GRS clinics market themselves almost exclusively to non-Thai trans women (people assigned a male sex at birth who later identify as female). This article draws on ethnographic research with patients visiting Thailand for GRS to explore how trans women patients related their experience of medical care in Thailand to Thai cultural traditions, in particular "traditional" Thai femininity and Theravada Buddhist rituals and beliefs. Foreign patients in Thai hospital settings engage not only with medical practices but also with their perceptions of Thai cultural traditions--which inflect their feminine identifications. I draw on two patients' accounts of creating personal rituals to mark their gender reassignment surgery, placing these accounts within the context of biomedical globalization and debates about the touristic appropriation of non-"Western" cultural practices. | 10.1080/01459740.2010.501314 |
pubmed_150_7955 | PURPOSE
The goal of this study was to describe how ultra-lightweight wheelchair users use their wheelchairs during everyday mobility.
METHOD
We instrumented a convenience sample of 69 ultra-lightweight wheelchair users with a seat switch to measure their occupancy, and an accelerometer on their wheel to measure distance wheeled, time spent wheeling and daily bouts of mobility.
RESULTS
On the median day, subjects wheeled 83 bouts and 1.4 km over 45 min. A typical bout of mobility was 8.3 m in length, lasting 20 s and occurring at a speed of 0.44 m/s. Fast (>1 m/s) and long (>2 min) bouts represented less than 4% of bouts and were more common among younger participants and those who were employed or a student.
CONCLUSIONS
Highly functional manual wheelchair users present with a significant mobility disability, moving far less than their ambulating peers despite moving with similar mobility characteristics. The typical bout characteristics - short and slow bouts - are consistent with indoor mobility and transitions between functional activities. For wheelchair users, it highlights the importance of manoeuverability and the need for prescription and training to emphasize manoeuverability. Implications for Rehabilitation Measurement of wheelchair use, both how and how much, might provide unique insight to what equipment would be most appropriate for an individual. Participants who used an ultralight wheelchair presented with a significant mobility disability, wheeling only 1.7 km/day on average. Fast (>1 m/s) and long (>2 min) bouts are uncommon, representing less than 4% of bouts. Younger participants and those who were employed or a student were more likely to wheel one fast and long bout per day. Because wheelchair mobility was dominated by short, slow bouts, prescription and training need to emphasize maneuverability. | 10.1080/17483107.2016.1178819 |
pubmed_773_10377 | 1. (-)-Isoprenaline-induced positive inotropic effects were assessed in driven left atria and positive chronotropic effects in spontaneously beating right atria from guinea-pigs and cats. 2. Hydrocortisone produced dose dependent shifts to the left in cumulative concentration-effect curves to (-)-isoprenaline in left and right atrial preparations from the cat. 3. Maximal potentiations were produced by 160 muM and 40 muM hydrocortisone in cat left and right atria respectively. 4. No such effects were seen in similar preparations from the guinea-pig even in the presence of concentrations of hydrocortisone as high as 400 muM. 5. Hydrocortisone inhibited the extraneuronal uptake of [7 - 3H](-)-isoprenaline in a concentration dependent manner in both left and right atria of the cat, but not the guinea-pig. 6. These results are consistent with the idea that hydrocortisone potentiates responses to (-)-isoprenaline in cat atria by inhibition of the extraneuronal uptake process. | 10.1111/j.1440-1681.1976.tb02668.x |
pubmed_527_22032 | AIM
The aim of this study was to investigate foot deformities in patients with rheumatoid arthritis (RA), to detect frequency of deformities and to assess the relationship between foot deformities and foot functions.
METHODS
Anteroposterior and lateral radiographs of 40 patients and 40 control subjects were studied. The hallux valgus (HV) angle, intermetatarsal angle between first and second metatarsals, intermetatarsal angle between first and fifth metatarsals, and calcaneal pitch were measured on radiographs. Foot functions were measured by the Foot and Ankle Outcome Score (FAOS).
RESULTS
The frequency of foot deformities in RA patients was determined as 78.8%. The most frequent foot deformity in RA patients was HV (62.5%), followed by metatarsus primus varus (MPV) (41.3%). MPV and splaying of the forefoot deformities were significantly more frequent in RA patients than the control group (P < 0.05). Mild to moderate effect on FAOS subscales was observed in RA patients. There was a slight, but significant correlation between the foot deformities and the FAOS subscales except for quality of life subscale.
CONCLUSIONS
In this study, it has been shown that foot deformities are frequent in patients with RA and that there is slight deterioration in foot functions related to RA. Our results indicated that foot deformities have small, but clinically important changes on foot functions. There is a need for more studies, which evaluates the foot deformities, to further explore the relationship between the foot deformities and foot function in patients with RA. | 10.1111/j.1756-185X.2010.01465.x |
pubmed_571_15782 | BACKGROUND
Cognitive insight phenomenon lies at the core of numerous discoveries. Behavioral research indicates four salient features of insightful problem solving: (i) mental impasse, followed by (ii) restructuring of the problem representation, which leads to (iii) a deeper understanding of the problem, and finally culminates in (iv) an "Aha!" feeling of suddenness and obviousness of the solution. However, until now no efforts have been made to investigate the neural mechanisms of these constituent features of insight in a unified framework.
METHODOLOGY/PRINCIPAL FINDINGS
In an electroencephalographic study using verbal remote associate problems, we identified neural correlates of these four features of insightful problem solving. Hints were provided for unsolved problems or after mental impasse. Subjective ratings of the restructuring process and the feeling of suddenness were obtained on trial-by-trial basis. A negative correlation was found between these two ratings indicating that sudden insightful solutions, where restructuring is a key feature, involve automatic, subconscious recombination of information. Electroencephalogram signals were analyzed in the space x time x frequency domain with a nonparametric cluster randomization test. First, we found strong gamma band responses at parieto-occipital regions which we interpreted as (i) an adjustment of selective attention (leading to a mental impasse or to a correct solution depending on the gamma band power level) and (ii) encoding and retrieval processes for the emergence of spontaneous new solutions. Secondly, we observed an increased upper alpha band response in right temporal regions (suggesting active suppression of weakly activated solution relevant information) for initially unsuccessful trials that after hint presentation led to a correct solution. Finally, for trials with high restructuring, decreased alpha power (suggesting greater cortical excitation) was observed in right prefrontal area.
CONCLUSIONS/SIGNIFICANCE
Our results provide a first account of cognitive insight by dissociating its constituent components and potential neural correlates. | 10.1371/journal.pone.0001459 |
pubmed_1044_13672 | AIMS
Stimulation of peripheral chemoreceptors, as during hypoxia, increases breathing and respiratory-related sympathetic bursting. Activation of catecholaminergic C1 neurones induces sympathoexcitation, while its ablation reduces the chemoreflex sympathoexcitatory response. However, no study has determined the respiratory phase(s) in which the pre-sympathetic C1 neurones are recruited by peripheral chemoreceptor and whether C1 neurone activation affects all phases of respiratory modulation of sympathetic activity. We addressed these unknowns by testing the hypothesis that peripheral chemoreceptor activation excites pre-sympathetic C1 neurones during inspiration and expiration.
METHODS
Using the in situ preparation of rat, we made intracellular recordings from baroreceptive pre-sympathetic C1 neurones during peripheral chemoreflex stimulation. We optogenetically activated C1 neurones selectively and compared any respiratory-phase-related increases in sympathetic activity with that which occurs following stimulation of the peripheral chemoreflex.
RESULTS
Activation of peripheral chemoreceptors using cytotoxic hypoxia (potassium cyanide) increased the firing frequency of C1 neurones and both the frequency and amplitude of their excitatory post-synaptic currents during the phase of expiration only. In contrast, optogenetic stimulation of C1 neurones activates inspiratory neurones, which secondarily inhibit expiratory neurones, but produced comparable increases in sympathetic activity across all phases of respiration.
CONCLUSION
Our data reveal that the peripheral chemoreceptor-mediated expiratory-related sympathoexcitation is mediated through excitation of expiratory neurones antecedent to C1 pre-sympathetic neurones; these may be found in the Kölliker-Fuse nucleus. Despite peripheral chemoreceptor excitation of inspiratory neurones, these do not trigger C1 neurone-mediated increases in sympathetic activity. These studies provide compelling novel insights into the functional organization of respiratory-sympathetic neural networks. | 10.1111/apha.13853 |
pubmed_491_16458 | OBJECTIVES
To compare the clinical outcomes of operative and nonoperative treatment for displaced intra-articular calcaneal fractures (DIACFs).
DATA SOURCES
PubMed, Embase, Cochrane library, and ClinicalTrial.gov.
STUDY SELECTION
Randomized controlled trials comparing operative and nonoperative treatment for DIACFs.
DATA EXTRACTION
Information on study methods and clinical outcomes.
DATA SYNTHESIS
We performed data synthesis on relevant clinical outcomes. Weighted mean differences with 95% confidence intervals were calculated for continuous data and relative risks with 95% confidence intervals were calculated for dichotomous data. A fixed-effect model or a random-effect model was used.
RESULTS
Seven randomized controlled trials involving 908 patients were included. Operative treatment for DIACFs reduced problems associated with shoe wear and increased walking ability but increased the risks of overall complications and infection. There were no significant differences between the groups in American Orthopaedic Foot and Ankle Society scores, The Short Form (36) Health Survey, return to work, rate of subsequent subtalar fusion, or the rate of reflex sympathetic dystrophy.
CONCLUSIONS
This meta-analysis documented that when surgery was performed correctly, better shoe wear and improved walking ability could be expected. These outcomes seemed to be based on the surgeon's ability to obtain an acceptable reduction. Benefits were tempered by the increase in wound complications associated with this intervention.
LEVEL OF EVIDENCE
Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence. | 10.1097/BOT.0000000000000446 |
pubmed_1052_4574 | PURPOSE
To analyze the cases of lamina resorption following the modified osteo-odonto-keratoprosthesis (MOOKP) procedure.
DESIGN
Retrospective case series.
PATIENTS AND METHODS
Case records of 18 eyes (20 laminae) of 17 patients who showed evidence of lamina resorption out of the 85 eyes (87 laminae) of 82 patients that underwent MOOKP procedure between March 2003 and March 2013 were analyzed.
RESULTS
Of the 17 patients (20 laminae), 1 underwent MOOKP procedure following multiple graft failures, 6 (7 laminae) belonged to the chemical injury group, and 10 (12 laminae) to the Stevens-Johnson syndrome (SJS) group. Resorption was noted in 20 out of 87 laminae (22.98%). The need for removal of lamina/extrusion was noted in 3 out of the 7 laminae in the chemical injury group and 8 out of the 12 laminae in the SJS group. The mean duration to the first sign suggestive of resorption among patients of SJS was 36.7 months and among patients of chemical injury was 43 months. Vitritis was the presenting feature (7 of 20 laminae, 35%) indicative of early resorption, and the occurrence of the same in eyes with lamina resorption was noted to be statistically significant in comparison to controls (P<.001). Sixteen out of 20 laminae showed evidence of resorption superiorly.
CONCLUSION
Vitritis was the most common presenting feature of lamina resorption and could be an indicator of lamina resorption. Resorption of the laminae was noted to occur along the aspect with thinner bone support in all eyes. Incidence of severe resorption with extrusion of cylinder/requiring lamina removal was noted to be higher among patients with SJS. | pubmed_1052_4574 |
pubmed_1051_22700 | INTRODUCTION
Rural health services face greater challenges in managing infectious patients due to lack of specialty beds and longer lengths of stay. The pressures of seasonal influxes of influenza patients with a heavy burden of chronic disease and an ageing population result in an increased demand for hospital beds. During these peak periods it is common for rural hospitals to experience bed block. The result is that patients may be placed into any available bed or ward at the time, increasing the need for transfer and the risk of spreading hospital-acquired respiratory illnesses to other patients and staff across the hospital. This further exacerbates bed block, with patients then requiring more specialised treatment and longer lengths of stay. This places additional strain on already existing workforce shortages and limited resources that must accommodate higher-than-normal patient loads. The objective of this study was to examine rural hospital bed management practices with a focus on the transfer of patients who are actively diagnosed with influenza (either on admission or during their stay in hospital) and to investigate the association of increased bed movement with the rate of nosocomial transmission and staff workload.
METHODS
The rates of patients admitted to a rural hospital in New South Wales, Australia, during the yearly peak influenza season (July to September) during 2016-2019 with either community-acquired or hospital-acquired influenza were examined using an infection control surveillance program. Bed management practices related to these inpatients were audited to examine their contribution towards nosocomial transmissions and staff workload during these periods.
RESULTS
A total of 229 patients presented to this hospital with an influenza diagnosis over the study period and generated 175 bed transfers. Forty percent of community-acquired and 70% of hospital-acquired influenza inpatients experienced one or more intrahospital bed transfers during their active infection period. Half of all bed transfers involved patients being transferred to another ward (interward) and the other half consisted of those transferred within the same ward (intraward). These transfers impacted staff workload, requiring a total of 245 extra hours from nursing and cleaning staff to facilitate - time not included when allocating staff at the start of each shift.
CONCLUSION
Findings from this study indicate that there is no active strategy for influenza containment during high-occupancy periods for this rural facility. This resulted in multiple bed transfers occurring during the active phase of influenza infection. This then led to an exacerbation of bed block and thus further inappropriate placement of newly admitted patients. The development of an optimal bed management plan for future surges of influenza and other highly infectious respiratory illnesses is essential to reduce nosocomial infection and staff workload, especially given the limited resources available in rural areas compared to metropolitan centres. | 10.22605/RRH7015 |
pubmed_895_3888 | GerW (formerly called YtfJ) is a protein found in dormant spores of Bacillus subtilis. We have studied spore proteins in B. subtilis before, and here we report the characterization of GerW protein. Northern blot analysis revealed that gerW mRNA was transcribed by SigF-containing RNA polymerase beginning 1 h after the initiation of sporulation. Fluorescence was detected in forespores and dormant spores of B. subtilis recombinant strains expressing GerW-GFP. During germination in the presence of L-alanine or a mixture of L-asparagine, D-glucose, D-fructose and potassium ions (AGFK), normal spores of B. subtilis became darkened, stained positive with Hoechst 33342 and carboxyfluorescein diacetate succinimidyl ester (CFDA-SE), and released dipicolinic acid (DPA). In the case of gerW-deficient spores, AGFK triggered germination in a manner similar to that seen in the wild-type spores, whereas spores stimulated by L-alanine remained refractive under the phase contrast microscope, failed to stain positive with Hoechst 33342 or CFDA-SE, and released almost no DPA. These results indicate that GerW is essential for the L-alanine-induced breakdown of spore dormancy followed by core rehydration and the resumption of enzymatic activity, and suggest that GerW is involved in the early stages of germination in the presence of l-alanine. | 10.1093/jb/mvt072 |
pubmed_835_14715 | BACKGROUND
Reexcision after breast-conserving surgery (BCS) is costly for patients, but few studies have captured the economic burden to a healthcare system. We quantified operating room (OR) charges as well as OR time and then modeled expected savings of a reexcision reduction initiative.
METHODS
We performed a retrospective cohort review of all breast cancer patients with BCS between January 1, 2016 and December 31, 2020. Operating room charges of disposable supplies and implants as well as operative time were calculated.
RESULTS
During the 5-year period, the 8804 patients who underwent BCS, 1628 (18.5%) required reexcision. The reexcision cohort was younger (61 vs. 64 years, p < 0.001), more likely to have ductal carcinoma in situ (DCIS) (23.7% vs. 15.2%, p < 0.001), and had larger tumors (T1+T2 73.2% vs. 83.1%, p < 0.001). Reexcision costs represented 39% of total costs, the cost per patient for surgery was fourfold higher for reexcision patients. Reexcision operations comprised 14% of total operating room (OR) time (1848 of 13,030 hours). The reexcision rate for 54 surgeons varied from 7.2-39.0% with 46% (n = 25) having a reexcision rate >20%. A model simulating reducing reexcision rates to 20% or below for all surgeons reduced the reexcision rate to 16.2% overall. Using per procedure data, the model predicted a decrease in reexcision operations by 18% (327 operations), OR costs by 14% ($287,534), and OR time by 11% (204 hours).
CONCLUSIONS
Reexcision after BCS represents 39% of direct OR costs and 14% of OR time in our healthcare system. Modest improvements in surgeon reexcision rates may lead to significant economic and OR time savings. | 10.1245/s10434-022-12127-6 |
pubmed_219_17446 | PURPOSE
The treatment mode in acute vertebrobasilar occlusion (VBO) remains uncertain. We analyzed efficacy and safety of intravenous glycoprotein IIb/IIIa inhibitor (IV GPI) plus subsequent intra-arterial thrombolysis with or without additional endovascular mechanical therapy (percutaneous transluminal angioplasty/stenting or thrombus aspiration) and sought treatment factors that predict good clinical outcome.
METHODS
We retrospectively analyzed 120 cases of patients with angiographically proven acute VBO. Multivariate logistic regression was used to identify independent predictors for clinical outcome and included level of consciousness, age, sex, time to angiography, GPI agent, admission mode, occlusion type, recanalization success, and endovascular treatment mode. Clinical follow-up was dichotomized in no to moderate disability (modified Rankin scale (mRS) 0-3) vs. severe disability or death (mRS 4-6).
RESULTS
Median National Institutes of Health stroke scale (NIHSS) score on admission was 32, and mean NIHSS score was 24. A total of 49 patients (41 %) developed no to moderate disability (mRS 0-3), and 39 patients (33 %) died. Thrombolysis in myocardial infarction 2/3 recanalization success was achieved in 97 patients (80.8 %). Symptomatic intracerebral hemorrhages occurred in 11 patients (9 %). Mild impairment of consciousness (p < 0.001) and embolic occlusion type (p = 0.01) were significant predictors of favorable outcome. Clinical outcome in recanalized patients was better, but not statistically significant (p = 0.055).
CONCLUSIONS
Our results indicate that combined therapy with IV GPI and subsequent endovascular therapy may be a valid treatment strategy in acute VBO. With this treatment approach, a preserved vigilance before treatment and an embolic occlusion type are associated with no to moderate disability. | 10.1007/s00062-014-0341-3 |
pubmed_916_20630 | The purpose of this study was to determine which variables of the range of motion (ROM) and strength of the hip, and ankle are associated with squat depth. In total, 101 healthy subjects (64 males, 37 females) participated in the study. Outcome measures consisted of the ROM of hip flexion, hip internal rotation, external rotation, ankle dorsiflexion with an extended and flexed knee joint, and strength of the hip flexor and ankle dorsiflexor. Squat depth was measured using SIMI motion analysis software. Pearson correlation was used to determine the relationship between variables and squat depth. Multiple stepwise regression analysis was performed to determine variables associated with squat depth. The multiple regression model indicated that ankle dorsiflexion with a flexed knee and the hip flexion ROM were significantly associated with squat depth in male subjects (R(2) = 0.435) and ankle dorsiflexion with an extended knee and dorsiflexor strength were significantly associated with squat depth in female subjects (R(2) = 0.324). Thus, exercises to increase the ROM of the ankle dorsiflexion, hip flexion, and dorsiflexor strength can be recommended to improve squat performance. Future studies should assess an increased ROM of the ankle dorsiflexion, hip flexion, or dorsiflexor strength effect on deep squat performance. | 10.1515/hukin-2015-0007 |
pubmed_986_2089 | Evidence is presented indicating that norepinephrine (NE) inhibits vasopressin (VP) release from the rat hypothalamo-neurohypophyseal explant under some, but not all, conditions in vitro. NE at 10(-5) M inhibited basal VP release and inhibited acetylcholine-induced release in a concentration-dependent fashion. However, the induction of VP release caused by the addition of NaCl (sufficient to yield a 10 mosmol/kg H2O increase in culture medium osmolality) was not reduced by NE in concentrations as high as 10(-5) M. An alpha-adrenergic receptor mediation of the inhibition of VP release by NE was suggested by the ability of phentolamine and phenoxybenzamine, but not propranolol, to block this effect. In addition, phentolamine at 10(-4) M, but not equimolar amounts of propranolol, increased VP release when added alone on day 2 of culture, but not on days 3 or 4. Histofluorescence examination of additional explants revealed that endogenous catecholamine was still present on day 2 within varicosities in the supraoptic nucleus, but diminished by days 3 and 4, suggesting that endogenous NE could influence basal VP release. The results indicate that NE can inhibit spontaneous and cholinergically stimulated VP release from the hypothalamo-neurohypophyseal explant, but osmotic stimulation renders the explants insensitive to attenuation of VP release by NE. | 10.1210/endo-111-1-273 |
pubmed_1096_13914 | Tetracyanide building block [Cr(2,2'-bipy)(CN)(4)]- and two bicompartimental Schiff-base based manganese(III) compounds have been employed to assemble cyanide-bridged heterometallic complexes, resulting in two cyanide-bridged CrIII-MnIII complexes: [Mn(L(1))(H(2)O)][Cr(2,2'-bipy)(CN)(4)]·CH(3)OH·2.5H(2)O (1) and [Mn(L(2))(H(2)O)][Cr(2,2'-bipy)(CN)(4)]·CH(3)OH·(3)H(2)O (2) (L1 = N,N'-(1,3-propylene)-bis(3-methoxysalicylideneiminate), L2 = N,N'-ethylene-bis(3-ethoxysalicylideneiminate)). Single X-ray diffraction analysis shows their similar cyanide-bridged binuclear structures, in which the cyanide precursor acting as monodentate ligand connects the manganese(III) ion. The binuclear complexes are self-complementary through coordinated aqua ligand and the free O4 compartment from the neighboring complex, giving H-bond linking dimer structure. Investigation over magnetic properties reveals the antiferromagnetic magnetic coupling between the cyanide-bridged Cr(III) and Mn(III) ions. A best-fit to the magnetic susceptibilities of these two complexes leads to the magnetic coupling constants J = -5.95 cm(-1), j = -0.61 cm(-1) (1) and J = -4.15 cm(-1), j = -0.57 cm(-1) (2), respectively. | 10.17344/acsi.2014.1154 |
pubmed_484_16554 | BACKGROUND
Desmoplastic melanoma is an uncommon variant of cutaneous melanoma that mimics soft tissue sarcoma both clinically and morphologically. An activating point mutation of the BRAF oncogene has been identified in a high proportion of conventional cutaneous melanomas, but its frequency in the desmoplastic subtype is not known.
METHODS
The authors tested 12 desmoplastic melanoma specimens for the thymine (T)-->adenine (A) missense mutation at nucleotide 1796 of the BRAF gene using a newly developed assay that employs a novel primer extension method. They also tested 57 vertical growth phase cutaneous nondesmoplastic melanoma specimens.
RESULTS
The 1796 T-->A mutation was detected in 23 of the 57 conventional cutaneous melanoma specimens but in none of the 12 desmoplastic melanoma specimens (40% vs. 0%; P=0.0006, Fisher exact 2-tailed test).
CONCLUSIONS
The relative importance of BRAF mutational activation in melanocytic tumorigenesis clearly was not the same across the various subtypes of melanoma, even for melanomas of cutaneous origin that are associated with sun exposure. In contrast to conventional cutaneous melanomas, the desmoplastic variant frequently did not harbor an activating mutation of BRAF. Accordingly, patients with melanomas should not be collectively regarded as a uniform group as new therapeutic strategies are developed that target specific genetic alterations. | 10.1002/cncr.20861 |
pubmed_489_12973 | Water and gas samples were collected from (1) nine shallow groundwater aquifers overlying Marcellus Shale in north-central West Virginia before active shale gas drilling, (2) wells producing gas from Upper Devonian sands and Middle Devonian Marcellus Shale in southwestern Pennsylvania, (3) coal-mine water discharges in southwestern Pennsylvania, and (4) streams in southwestern Pennsylvania and north-central West Virginia. Our preliminary results demonstrate that the oxygen and hydrogen isotope composition of water, carbon isotope composition of dissolved inorganic carbon, and carbon and hydrogen isotope compositions of methane in Upper Devonian sands and Marcellus Shale are very different compared with shallow groundwater aquifers, coal-mine waters, and stream waters of the region. Therefore, spatiotemporal stable isotope monitoring of the different sources of water before, during, and after hydraulic fracturing can be used to identify migrations of fluids and gas from deep formations that are coincident with shale gas drilling. | 10.1111/gwat.12083 |
pubmed_431_10242 | The discovery of a coeliacomesenteric trunk is often fortuitous in a context of morphological or vascular exploration. About one case of this rare arterial remind us of its characteristic and different type. We emphasize the interest of not being unaware of this variation in radiological practice and vascular pathology. In our observation, the coeliacomesenteric trunk's ostium is oval with a tall axis of 14 mm; its route of 8mm is median and its arterial ending divide into hepatosplenogastric trunk and superior mesenteric trunk. It is a type I coeliacomesenteric trunk which is the most frequent type of this arterial variation in Higashi's classification. | 10.1016/j.morpho.2008.04.002 |
pubmed_76_2854 | Autologous bone marrow transplantation (ABMT) is widely used as treatment for malignant disease. Although the major cause of treatment failure is relapse, it is unknown if this arises entirely because of residual disease in the patient or whether contaminating cells in the rescuing marrow contribute. Attempts to purge marrow of its putative residual malignant cells may delay hematopoietic reconstitution and are of uncertain efficacy. We now describe how retrovirus-mediated gene transfer may be used to elucidate the source of relapse after ABMT for acute myeloid leukemia and to evaluate the efficacy of purging. Clonogenic myeloid leukemic blast cells in patient marrow can be transduced with the NeoR gene-containing helper-free retrovirus, LNL6, with an efficacy of 0% to 23.5% (mean, 10.5%). Transduced colonies grow in selective media and the presence of the marker gene can be confirmed in individual malignant colonies by polymerase chain reaction. If such malignant cells remain in harvested "remission" marrow, they will therefore be marked after exposure to LNL6. Detection of the marker gene in the malignant cells present at any later relapse would be firm evidence that residual disease contributed to disease recurrence, and would permit rapid subsequent evaluation of purging techniques. The technique also marks normal marrow progenitors from patients with acute myeloblastic leukemia. These colony-forming cells can be detected in long-term marrow cultures at a frequency of 1% to 18% for up to 10 weeks after exposure to the vector. Animal models and analysis of probability tables both suggest that these levels of marking in vitro are sufficient to provide information about the mechanisms of relapse and the biology of marrow regeneration in vivo. These preclinical data form part of the basis for current clinical studies of gene transfer into marrow before ABMT. | pubmed_76_2854 |
pubmed_629_17803 | Vitiligo is a depigmenting disorder resulting from the loss of melanocytes in the skin and affects 1-4% of the world population. Incidence of vitiligo is found to be 0.5-2.5% in India with a high prevalence of 8.8% in Gujarat and Rajasthan states. The cellular and molecular mechanisms that lead to melanocyte destruction in this disorder are not yet been fully elucidated. Genetic factors, neural factors, toxic ROS metabolites, autoantibodies and autoreactive T lymphocytes may be the causative agents for the selective destruction of melanocytes. Three major hypotheses of pathogenesis of vitiligo are neural, autoimmune and oxidative stress hypotheses, however none of them explains the pathogenesis of vitiligo in toto. Genetics of vitiligo is characterized by incomplete penetrance, multiple susceptibility loci and genetic heterogeneity. Recent advances in this field are linkage and association of candidate gene studies. The linkage and association studies provide a strong evidence for the presence of multiple vitiligo susceptibility genes on different chromosomes. Several candidate genes for vitiligo are identified from different populations. In this review, we have provide an overview of different hypotheses of vitiligo pathogenesis, and discuss the recent advances in this field with special reference to linkage, association and candidate gene approach. | pubmed_629_17803 |
pubmed_675_21949 | Yarrowia lipolytica is characterized by GRAS (Generally regarded as safe) status, the versatile substrate utilization profile, rapid utilization rates, metabolic diversity and flexibility, the unique abilities to tolerate to extreme environments (acidic, alkaline, hypersaline, heavy metal-pollutions and others) and elevated biosynthesis and secreting capacities. These advantages of Y. lipolytica allow us to consider it as having great ecological significance. Unfortunately, there is still a paucity of relevant review data. This mini-review highlights ecological ubiquity of Y. lipolytica species, their ability to diversify and colonize specialized niches. Different Y. lipolytica strains, native and engineered, are beneficial in degrading many environmental pollutants causing serious ecological problems worldwide. In agriculture has a potential to be a bio-control agent by stimulating plant defense response, and an eco-friendly bio-fertilizer. Engineered strains of Y. lipolytica have become a very promising platform for eco-friendly production of biofuel, commodities, chemicals and secondary metabolites of plant origin, obtaining which by other method were limited or economically infeasible, or were accompanied by stringent environmental problems. Perspectives to use potential of Y. lipolytica's capacities for industrial scale production of valuable compounds in an eco-friendly manner are proposed. | 10.1093/femsyr/foab008 |
pubmed_883_3325 | The discovery of the radio frequency lines of OH gave the first positive evidence of the existence of OH in the interstellar medium. In the 3(1/2) years that have intervened, many observations have revealed totally unexpected anomalies in the radio-spectral properties of interstellar OH. As a result, no reliable astrophysical information has been derived from the OH observations, but a large body of information is waiting to be unraveled. The interpretations of the data which have been made, such as the values derived for OH/H abundance ratios or for the kinetic temperatures of interstellar gas clouds, must be viewed with caution. They may turn out to be drastically in error, once the origin of the OH emission and absorption is fully understood. | 10.1126/science.157.3791.881 |
pubmed_229_11144 | OBJECTIVE
To estimate the annual number and costs of coronary heart disease (CHD) events in the United States attributable to insulin resistance among individuals with and without type 2 diabetes.
RESEARCH DESIGN AND METHODS
Medline-indexed articles and government statistical reports were screened for data on the prevalence of insulin resistance, the relative risk of CHD by insulin resistance status, and number of CHD events per year among individuals with and without type 2 diabetes. These data were used to estimate the number of CHD events per year by insulin resistance and type 2 diabetes status, the proportion of CHD events attributable to insulin resistance, and the annual cost of these events.
RESULTS
Of the 171,000 annual CHD events in the type 2 diabetes population, 164,000 (96%) occurred in those with insulin resistance, 80,000 of which were attributable to insulin resistance. Of the 929,000 annual CHD events in the non-type 2 diabetes population, 162,000 (17%) occurred in patients with insulin resistance, 58,000 of which were attributable to insulin resistance. Thus, insulin resistance is responsible for 46.8%, 6.2%, and 12.5% of the annual CHD events in the type 2 diabetes, non-type 2 diabetes, and total US population, respectively. The estimated annual total cost of these insulin resistance-attributable events was $12.5 billion in the United States in 1999, of which $6.6 billion were direct medical costs.
CONCLUSION
Preventing or modifying insulin resistance may reduce the morbidity, mortality, and costs associated with CHD. | pubmed_229_11144 |
pubmed_229_17600 | A series of imidazolopyrazinones 3, substituted at C-2, and C-2/C-6, has been prepared. The compounds behaved as quenchers of superoxide anion. The more active compounds are structurally related to coelenterazine, a natural substrate of marine bioluminescence. Theoretical parameters based on Hartree-Fock instabilities have been examined. | 10.1016/s0960-894x(01)00445-0 |
pubmed_9_12408 | This relatively new form of laser energy, with its powerful and precise ability to ablate the dense tissues of the musculoskeletal system as well as its transmissibility in fiberoptic cables and a fluid medium, makes this an ideal tool for use in orthopedic surgery. Its importance as a new orthopedic modality may well lie in its unique ability to gain access to small articular compartments while providing superior homeostatic control, thereby decreasing postoperative morbidity. While not yet in widespread use, its popularity is rapidly spreading and research into a variety of new applications is growing steadily. | 10.3928/0147-7447-19930501-09 |
pubmed_943_106 | The degree of medical adherence in pediatric solid-organ transplant recipients frequently correlates with the degree of psychological distress, family functioning, and the physiological side-effects of immunosuppressant medications. This article examines the current literature regarding each of these factors and proposes recommendations for increasing the medical compliance among childhood transplant recipients. | 10.1034/j.1399-3046.2001.005004246.x |
pubmed_195_10966 | Stable topological defects of light (pseudo)scalar fields can contribute to the Universe's dark energy and dark matter. Currently, the combination of gravitational and cosmological constraints provides the best limits on such a possibility. We take an example of domain walls generated by an axionlike field with a coupling to the spins of standard-model particles and show that, if the galactic environment contains a network of such walls, terrestrial experiments aimed at the detection of wall-crossing events are realistic. In particular, a geographically separated but time-synchronized network of sensitive atomic magnetometers can detect a wall crossing and probe a range of model parameters currently unconstrained by astrophysical observations and gravitational experiments. | 10.1103/PhysRevLett.110.021803 |
pubmed_713_21249 | The present paper advances the proposition that level of opposition to immigration (i.e., endorsement of closure or exclusion) and its sources are not uniform and vary across immigrant groups. To test this proposition we utilize data from the 2014 European Social Survey for 20 countries and apply the analysis to the following groups: immigrants of same race/ethnic group as a majority population, immigrants of different race/ethnic group, Muslim, Jewish, and Roma immigrants. The analysis reveals that level of opposition to immigration of different ethno-religious groups in Europe is hierarchical, being most extreme toward Muslims and Roma and quite minor toward people of the same ethnic/race groups as well as toward Jews. Further analysis reveals that not only the level of opposition varies across groups but also the sources that drive such opposition. In general, the sources of opposition to immigration can be divided to 2 major categories: universal sources and group-specific sources. The universal sources (sources which increase opposition toward all immigrants regardless of their origin) pertain to threat of competition over socio-economic and symbolic resources. The group-specific sources consist of racism, fear of crime, and inter-group contact. Racism and lack of inter-group contact tend to increase opposition that is exclusive to Muslim and to Roma immigrants. Racism, however, does not increase opposition that is exclusive to immigrants belonging to a race/ethnicity, which is different from most country people. Fear of crime is likely to prompt opposition that is exclusive to immigrants of different race/ethnic group and to Roma but not toward Muslims. The findings underscore the multiple sources underlying emergence of anti-immigrant sentiment, in general, and opposition to specific groups of immigrants, in particular. | 10.3389/fsoc.2019.00024 |
pubmed_358_10851 | PURPOSE
The ketogenic diet has been used for treating seizure disorders for more than 70 years. Nephrolithiasis is a known complication of this diet with a reported stone rate as high as 10% but there is sparse literature detailing the nature and treatment of these stones. We report on 4 children with nephrolithiasis on this diet.
MATERIALS AND METHODS
We describe stone treatment and analysis as well as metabolic and urine abnormalities in 4 children with nephrolithiasis on the ketogenic diet who presented to our institution.
RESULTS
All patients were treated with shock wave lithotripsy, fluid liberalization and oral citrate. One child was ultimately withdrawn from the diet due to persistent stone formation. Analysis revealed 3 calcium and 1 ammonium urate stones. Three patients had hypercalciuria, 2 elevated urinary uric acid and 1 hypocitruria. Serum studies revealed acidosis in 3 cases.
CONCLUSIONS
The ketogenic diet induces several metabolic abnormalities that increase the propensity for stone formation. Urologists should be aware of this potential complication. Fluid liberalization and bicitrate are recommended as prophylaxis. | pubmed_358_10851 |
pubmed_537_2052 | 'Blown pack' spoilage of vacuum-packed chilled beef, lamb and venison, and of a cooked meat product, chilled dog rolls packed in an oxygen-impermeable plastic casing, was characterised by sensory, chemical and microbiological analysis. Investigation of the probable causative agents led to the isolation of eight strains of psychrotrophic clostridia. Three strains have been provisionally identified as C. difficile, C. beijerinckii and C. lituseburense; the other five remain unidentified. In inoculation studies only one isolate produced significant amount of gas on meat, causing pack 'blowing'. It is, therefore, possible that 'blown pack' spoilage involves a synergism with one or more other organisms. | 10.1016/0168-1605(95)00070-4 |
pubmed_87_20534 | Targeted therapy based on ALK tyrosine kinase inhibitors (ALK-TKIs) has made significant achievements in individuals with EML4-ALK (echinoderm microtubule-associated protein-like 4 gene and the anaplastic lymphoma kinase gene) fusion positive nonsmall-cell lung cancer (NSCLC). However, a high fraction of patients receive inferior clinical response to such treatment in the initial therapy, and the exact mechanisms underlying this process need to be further investigated. In this study, we revealed a persistently activated PI3K/AKT signaling that mediates the drug ineffectiveness. We found that genetic or pharmacological inhibition of ALK markedly abrogated phosphorylated STAT3 and ERK, but it failed to suppress AKT activity or induce apoptosis, in EML4-ALK-positive H2228 cells. Furthermore, targeted RNA interference of PI3K pathway components restored sensitivity to TAE684 treatment at least partially due to increased apoptosis. Combined TAE684 with PI3K inhibitor synergistically inhibited the proliferation of EML4-ALK-positive cells in vitro and significantly suppressed the growth of H2228 xenografts in vivo, suggesting the potential clinical application of such combinatorial therapy regimens in patients with EML4-ALK positive lung cancer. | 10.1007/s13277-014-2252-y |
pubmed_293_15590 | PURPOSE
The choice of urinary diversion at cystectomy is a life altering decision. Patient decision aids are clinical tools that promote shared decision making by providing information about management options and helping patients communicate their values. We sought to develop and evaluate a patient decision aid for individuals undergoing cystectomy with urinary diversion.
MATERIALS AND METHODS
We used the IPDAS (International Patient Decision Aids Standards) to guide a systematic development process. A literature review was performed to determine urinary diversion options and the incidence of outcomes. We created a prototype using the Ottawa Decision Support Framework. A 10-question survey was used to assess patient decision aid acceptability among patients, allied health professionals and urologists. The primary outcome was acceptability of the patient decision aid.
RESULTS
Ileal conduit and orthotopic neobladder were included as primary urinary diversion options because they had the most evidence and are most commonly performed. Continent cutaneous diversion was identified as an alternative option. Outcomes specific to ileal conduit were stomal stenosis and parastomal hernia. Outcomes specific to neobladder were daytime and nighttime urinary incontinence and urinary retention. Acceptability testing was completed by 8 urologists, 9 patients and 1 advanced practice nurse. Of the respondents 94% reported that the language was appropriate, 94% reported that the length was adequate and 83% reported that option presentation was balanced. The patient decision aid met all 6 IPDAS defining criteria, all 6 certification criteria and 21 of 23 quality criteria.
CONCLUSIONS
We created a novel patient decision aid to improve the quality of decisions made by patients when deciding among urinary diversion options. Effectiveness testing will be performed prospectively. | 10.1097/JU.0000000000000341 |
pubmed_1014_23760 | Tryptophan and arginine rich antimicrobial peptides (AMPs) possess high potencies against both gram positive and gram negative bacteria, while lipopeptides represent another family of promising antimicrobial agents to combat invading pathogens. In the present study, we have synthesized a series of very short arginine, lysine and tryptophan containing lipopeptides and evaluated their antimicrobial activities against a panel of pathogenic microorganisms including Staphylococcus aureus, Escherichia coli, and Candida albicans. The results showed that most of these peptides were effective against tested strains with MIC values ranging from 3.9 to 62.5 μg/mL. In addition to the small size, potent bactericidal activity, low to moderate hemolytic toxicity and membrane disruption ability, several peptides such as C10-RIKWWK and C10-RKWWK apparently retarded the migration of DNA on agarose gel in the DNA-binding assay, which implied the multiple modes of action in their bacteria-killing mechanism. These peptides revealed a promising therapeutic potential to develop as new antimicrobial agents. | pubmed_1014_23760 |
pubmed_1027_19158 | A 7-year-old spayed female Siamese cat was presented with a 7-day history of ataxia, circling to the right, and involuntary micturition and defecation. Cerebrospinal fluid analysis showed increased protein content and relative eosinophilia. At necropsy, there was flattening of the cerebral cortical gyri of the right frontal and parietal lobes, and both kidneys had multiple wedge-shaped cortical indentations. Histologically, the cerebral cortex contained several extensive malacic foci, and the kidneys had multifocal parenchymal degeneration and atrophy. There was multifocal partial to complete thrombosis of renal interlobar arteries and of the right middle cerebral artery and meningeal branches; these thrombi contained large anaplastic round cells, which often invaded the arterial wall. Many smaller vessels within the kidneys and brain were occluded with clusters of similar cells, without thrombosis or vascular wall invasion. The neoplastic round cells had immunohistochemical staining properties of T lymphocytes. | 10.1177/030098589703400314 |
pubmed_278_17696 | Gall bladder perforation (GBP) is a rare and life-threatening complication of acute cholecystitis that requires immediate intervention. The diagnosis itself poses a diagnostic challenge, if the patient presents after the perforation of the gall bladder, especially if the initial imaging techniques such as ultrasonogram (US), computed tomography (CT) scan, hepatobiliary iminodiacetic acid (HIDA) scan and magnetic resonance cholangiopancreatography (MRCP) are inconclusive. Subtle clues such as free fluid around gall bladder and contracted gall bladder should warrant the clinician as these might be the only clues suggestive of gall bladder perforation. Here we describe a case of GBP successfully diagnosed by peritoneal drainage and analysis and subsequently managed by endoscopic retrograde cholangiopancreatography (ERCP) and open cholecystectomy. | 10.7759/cureus.14247 |
pubmed_101_3699 | PURPOSE
Multiple myeloma (MM) remains incurable and its diagnosis relies heavily on bone marrow aspiration and biopsy. CD38 is a glycoprotein highly specific for MM. Antibody therapeutics (e.g., daratumumab) targeting CD38 have shown encouraging efficacy in treating MM, either as a monotherapy agent or in combination with other regimens. However, efficient stratification of patients who might benefit from daratumumab therapy and timely monitoring of the therapeutic responses are still clinical challenges. This work aims to devise a CD38-targeted imaging strategy and assess its value in diagnosing MMs.
METHODS
By labeling a CD38-specific single domain antibody (Nb1053) with 68Ga (t1/2 = 1.1 h), we developed a CD38-targeted immuno-positron emission tomography (immunoPET) imaging probe [68Ga]Ga-NOTA-Nb1053. The probe was developed with good radiochemical yield (> 50%), excellent radiochemical purity (> 99%), and immunoreactivity (> 95%). The diagnostic accuracy of the probe was thoroughly investigated in preclinical MM models.
RESULTS
ImmunoPET imaging with [68Ga]Ga-NOTA-Nb1053 specifically depicted all the subcutaneous and orthotopic MM lesions, outperforming the traditional 18F-fluorodeoxyglucose PET and the nonspecific [68Ga]Ga-NOTA-NbGFP immunoPET. More importantly, daratumumab preloading significantly reduced [68Ga]Ga-NOTA-Nb1053 uptake in the disseminated bone lesions, indicating the overlapping targeting epitopes of [68Ga]Ga-NOTA-Nb1053 with that of daratumumab. Furthermore, premedication with sodium maleate or fructose significantly decreased kidney retention of [68Ga]Ga-NOTA-Nb1053 and improved the diagnostic value of the probe in lymphoma models.
CONCLUSION
This work successfully developed a novel CD38-targeted immunoPET imaging approach that enabled precise visualization of CD38 and diagnosis of MMs. Upon clinical translation, [68Ga]Ga-NOTA-Nb1053 immunoPET may serve as a valuable CD38-targeted molecular imaging toolbox, facilitating early diagnosis of MM and precise assessment of the therapeutic responses. | 10.1007/s00259-021-05218-1 |
pubmed_828_24776 | The activation of cAMP-response element binding protein (CREB)-dependent gene expression seems a crucial step in the molecular cascade that mediates the formation of long-lasting memories. This view is based both on correlative evidence and on functional assays that demonstrate, through loss- and gain-of-function experiments, the impact of CREB manipulation on memory performance. Mechanistically, CREB's role in memory is thought to be a consequence of its participation in long-term forms of synaptic plasticity. Recent studies demonstrate that CREB, in addition to synaptic plasticity, also modulates the intrinsic excitability of the neuron. This discovery reveals new intriguing connections between intrinsic and synaptic plasticity and is likely to have a significant impact on our understanding of the role of CREB in memory formation. | 10.1016/j.tins.2010.02.001 |
pubmed_806_4790 | OBJECTIVES
To examine patterns of associations between a broad range of mental and physical conditions by using a large, systematically obtained pediatric registry.
METHODS
The sample included 9014 youth ages 8 to 21 years (4349 males and 4665 females; 3585 aged <13 years, 3678 aged 13 to 18 years, and 1751 aged 19 to 21 years) from the Philadelphia Neurodevelopmental Cohort identified through pediatric clinics at the Children's Hospital of Philadelphia health care network by the Center for Applied Genomics. Measures were as follows: physical condition based on electronic medical records and interview data on 42 physical conditions of 14 organ systems/specialties and mental disorders based on an abbreviated version of the structured Kiddie-Schedule for Affective Disorders and Schizophrenia psychiatric diagnostic interview.
RESULTS
There was a direct association between the severity of the physical condition and most classes of mental disorders, as well as with functional impairment. Models adjusted for sociodemographic correlates, other physical and mental disorders, and false discovery and revealed broad patterns of associations between neurodevelopmental disorders with behavior disorders (odds ratio [OR]: 1.5; 95% confidence interval [CI]: 1.3-1.8; P < .004) and attention-deficit/hyperactivity disorder (OR: 3.1; 95% CI: 2.7-3.6; P < .0001), and neurologic/central nervous system conditions (OR: 1.3; 95% CI: 1.1-1.9; P < .05) with mood disorders and attention-deficit/hyperactivity disorder (OR: 1.3; 95% CI: 1.1-1.5; P < .001), and autoimmune/inflammatory conditions with mood disorders (OR: 1.4; 95% CI: 1.1-1.8, P < .05).
CONCLUSIONS
Findings show the strong overlap between physical and mental conditions and their impact on severity and functional impairment in youth. Specific patterns of comorbidity have important implications for etiology. Prospective tracking of cross-disorder morbidity will be important to establish more effective mechanisms for prevention and intervention. | 10.1542/peds.2014-1444 |
pubmed_18_13447 | The arboviral disease with the highest human incidence in South America is dengue fever. In French Guiana, where all four dengue serotypes, i.e., DENV-1, DENV-2, DENV-3 and DENV-4, are present, the disease is endemic with epidemic outbreaks. Though previous serological studies have suggested a sylvatic cycle, involvement of wild mammals in the dengue cycle in the neotropics has never been confirmed. The purpose of this study was to search for the presence of DENV in wild animals captured at two different sites between 2001 and 2007. About 10,000 trap/nights were performed leading to the capture of 464 non-flying mammals (rodents and marsupials). In addition, mistnests placed in the same zone yielded 152 bats. Reverse transcription-polymerase chain reaction amplification to detect infection by any of the four dengue serotypes demonstrated viral RNA in the livers and/or sera of 92 captured animals. Sequence analysis of amplification products revealed that the DENV-1, DENV-3 and DENV-4 serotypes were distinct from those circulating in humans at the same periods. Analysis for DENV-2 showed that some strains were divergent from concurrent human strains but that others were identical. The latter finding suggests that wild neotropical mammals living in periurban area can be infected by dengue virus strains circulating in humans. However, further investigation will be needed to determine if neotropical mammals are incidental hosts or potential reservoirs of dengue virus. | pubmed_18_13447 |
pubmed_1052_19778 | Porous materials are attractive for separation and catalysis-these applications rely on selective interactions between host materials and guests. In metal-organic frameworks (MOFs), these interactions can be controlled through a flexible structural response to the presence of guests. Here we report a MOF that consists of glycyl-serine dipeptides coordinated to metal centres, and has a structure that evolves from a solvated porous state to a desolvated non-porous state as a result of ordered cooperative, displacive and conformational changes of the peptide. This behaviour is driven by hydrogen bonding that involves the side-chain hydroxyl groups of the serine. A similar cooperative closure (reminiscent of the folding of proteins) is also displayed with multipeptide solid solutions. For these, the combination of different sequences of amino acids controls the framework's response to the presence of guests in a nonlinear way. This functional control can be compared to the effect of single-point mutations in proteins, in which exchange of single amino acids can radically alter structure and function. | 10.1038/nchem.1871 |
pubmed_1076_9602 | Geminiviruses have circular single-stranded DNA genomes and are important pathogens in tropical and subtropical regions, but their population diversity and variability are poorly understood. Here, we have investigated variations accumulating in Tomato yellow leaf curl China virus (TYLCCNV), a geminivirus in the genus Begomovirus of the family Geminiviridae. The population variation was analyzed in a naturally infected tomato (Solanum lycopersicom) plant and in Nicotiana benthamiana and tomato plants experimentally infected with a swarm of TYLCCNV DNA clones to provide an identical sequence for initiation of infection. Our results demonstrate that the population of TYLCCNV in a naturally infected tomato plant was genetically heterogeneous and that rapid mutation occurred in the populations amplified from N. benthamiana and tomato plants that had been infected with cloned DNA. This feature of the population of TYLCCNV in these plants consisted of the consensus sequence and a pool of mutants that are not identical but are closely related to the consensus sequence, and it coincides with the quasispecies concept described for many RNA viruses. The mutation frequency was circa 10(-4) in N. benthamiana and tomato at 60 days postinoculation, a value comparable to that reported for plant RNA viruses. The quasispecies-like nature of the TYLCCNV populations suggested that TYLCCNV is capable of rapid evolution and adaptation in response to changing agricultural practices. | 10.1128/JVI.02431-06 |
pubmed_845_8068 | This study aimed to assess the effect of caries increment on Oral Health-related Quality of Life (OHRQoL) of Brazilian adolescents and to evaluate the responsiveness of the Child Perceptions Questionnaire (CPQ11-14) in this group. A population-based sample of 515 Brazilian 12-year-olds from a large city located in the southeast of Brazil was evaluated according to a random multistage sampling design at baseline and 291 at three years follow-up, using the DMFT index and the CPQ11-14 instrument. To evaluate the responsiveness to change, the measures of effect size and longitudinal construct validity were used. It was verified that OHRQoL among adolescents with DMFT increment across the three years worsened significantly (p<0.05) in relation to their counterparts. The effect size varied from small to moderate. The longitudinal construct validity of CPQ11-14 was satisfactory. Caries increment impacted on OHRQoL of adolescents in Brazil. The CPQ11-14 instrument demonstrated acceptable responsiveness properties. | 10.1590/1807-3107bor-2020.vol34.0107 |
pubmed_325_18458 | PURPOSE
Guidelines for optimal transition call for multidisciplinary teams, including psychologists, to address youth and young adults' multifactorial needs. This study aimed to characterize psychologists' roles in and barriers to involvement in transition from pediatric to adult health care.
METHODS
Psychologists were invited via professional listservs to complete an online survey about practice settings, roles in transition programming, barriers to involvement, and funding sources. Participants also responded to open-ended questions about their experiences in transition programs.
RESULTS
One hundred participants responded to the survey. Involvement in transition was reported at multiple levels from individual patient care to institutional transition programming, and 65% reported more than one level of involvement. Direct clinical care (88%), transition-related research (50%), and/or leadership (44%) involvement were reported, with 59% reporting more than one role. Respondents often described advocating for their involvement on transition teams. Various sources of funding were reported, yet, 23% reported no funding for their work. Barriers to work in transition were common and included health care systems issues such as poor coordination among providers or lack of a clear transition plan within the clinic/institution.
CONCLUSIONS
Psychologists assume numerous roles in the transition of adolescents from pediatric to adult health care. With training in health care transition-related issues, psychologists are ideally positioned to partner with other health professionals to develop and implement transition programs in multidisciplinary settings, provided health care system barriers can be overcome. | pubmed_325_18458 |
pubmed_1123_20089 | Polyploidization plays an important role in plant speciation. The most recent estimates report that up to 15% of angiosperm speciation events and 31% in ferns are accompanied by changes in ploidy level. Polyploids can arise either through autopolyploidy, when the sets of chromosomes originate from a single species, or through allopolyploidy, when they originate from different species. In this study, we used two different coalescent-based methods to determine the date and mode of the polyploidization event that led to the tetraploid cosmopolitan weed, Capsella bursa-pastoris. We sampled 78 C. bursa-pastoris accessions, and 53 and 43 accessions from the only two other members of this genus, C. grandiflora and C. rubella, respectively, and sequenced these accessions at 14 unlinked nuclear loci with locus-specific primers in order to be able to distinguish the two homeologues in the tetraploid. A large fraction of fixed differences between homeologous genes in C. bursa-pastoris are segregating as polymorphisms in C. grandiflora, consistent with an autopolyploid origin followed by disomic inheritance. To test this, we first estimated the demographic parameters of an isolation-with-migration model in a pairwise fashion between C. grandiflora and both genomes of C. bursa-pastoris and used these parameters in coalescent simulations to test the mode of origin of C. bursa-pastoris. Second, we used Approximate Bayesian Computation to compare an allopolyploid and an autopolyploid model. Both analyses led to the conclusion that C. bursa-pastoris originated less than 1 Ma by doubling of the C. grandiflora genome. | 10.1093/molbev/mss024 |
pubmed_223_22131 | High blood cholesterol levels are often associated with cardiovascular diseases. Therapeutic strategies, targeting different functions involved in cholesterol transport or synthesis, were developed to control cholesterolemia in human. However, the gut microbiota is also involved in cholesterol regulation by direct biotransformation of luminal cholesterol or conversion of bile salts, opening the way to the design of new strategies to manage cholesterol level. In this report, we developed for the first time a whole-body human model of cholesterol metabolism including the gut microbiota in order to investigate the relative impact of host and microbial pathways. We first used an animal model to investigate the ingested cholesterol distribution in vivo. Then, using in vitro bacterial growth experiments and metabolite measurements, we modeled the population dynamics of bacterial strains in the presence of cholesterol or bile salts, together with their bioconversion function. Next, after correct rescaling to mimic the activity of a complex microbiota, we developed a whole body model of cholesterol metabolism integrating host and microbiota mechanisms. This global model was validated with the animal experiments. Finally, the model was numerically explored to give a further insight into the different flux involved in cholesterol turn-over. According to this model, bacterial pathways appear as an important driver of cholesterol regulation, reinforcing the need for development of novel "bacteria-based" strategies for cholesterol management. | 10.3389/fmicb.2020.01121 |
pubmed_929_21636 | BACKGROUND
High blood pressure is a major risk factor for cardiovascular disease and is influenced by both environmental and genetic factors. Epigenetic processes including DNA methylation potentially mediate the relationship between genetic factors, the environment and cardiovascular disease. Despite an increased risk of hypertension and cardiovascular disease in individuals of South Asians compared to Europeans, it is not clear whether associations between blood pressure and DNA methylation differ between these groups.
METHODS
We performed an epigenome-wide association study and differentially methylated region (DMR) analysis to identify DNA methylation sites and regions that were associated with systolic blood pressure, diastolic blood pressure and hypertension. We analyzed samples from 364 European and 348 South Asian men (first generation migrants to the UK) from the Southall And Brent REvisited cohort, measuring DNA methylation from blood using the Illumina Infinium® HumanMethylation450 BeadChip.
RESULTS
One CpG site was found to be associated with DBP in trans-ancestry analyses (i.e. both ethnic groups combined), while in Europeans alone seven CpG sites were associated with DBP. No associations were identified between DNA methylation and either SBP or hypertension. Comparison of effect sizes between South Asian and European EWAS for DBP, SBP and hypertension revealed little concordance between analyses. DMR analysis identified several regions with known relationships with CVD and its risk factors.
CONCLUSION
This study identified differentially methylated sites and regions associated with blood pressure and revealed ethnic differences in these associations. These findings may point to molecular pathways which may explain the elevated cardiovascular disease risk experienced by those of South Asian ancestry when compared to Europeans. | 10.1371/journal.pone.0227728 |
pubmed_512_15412 | BACKGROUND
Acute ozone (O3) exposure has known deleterious effects on the respiratory system and has been linked with respiratory disease and infection. Inflammatory lung disease induced by air pollution has demonstrated greater severity and poorer prognosis in women vs. men. Both severe damage to the bronchial-alveolar epithelium and malfunctioning of bronchial-blood barrier have been largely attributed to the pathobiology of O3-induced inflammatory response, but the associated mechanisms in the male and female lung remain unknown.
METHODS
Here, we investigated sex-based differential regulation of lung interleukin-6 (IL-6) and its downstream signaling pathways JAK2/STAT3 and AKT1/NF-κB in response to O3 exposure in a mouse model. We exposed male and female mice (in different stages of the estrous cycle) to 2 ppm of O3 or filtered air (FA) for 3 h, and we harvested lung tissue for protein expression analysis by Western blot.
RESULTS
We found significant up-regulation of IL-6 and IL-6R in females and IL-6 in males in response to O3 vs. FA. Ozone exposure induced a significant increase in STAT3-Y705 phosphorylation in both females and males. Males exposed to O3 had decreased levels of JAK2, but increased JAK2 (Y1007+Y1008) phosphorylation, while females exposed to O3 showed significant up-regulation of both proteins. Both NF-κB (p105/p50) and AKT1 protein levels were significantly increased only in females exposed to O3. In addition, females exposed to O3 during proestrus displayed increased expression of selected genes when compared to females exposed to O3 in other estrous cycle stages.
CONCLUSIONS
Together, our observations indicate a sex-based and estrous cycle-dependent differential lung inflammatory response to O3 and involvement of two converging JAK2/STAT3 and AKT1/NF-κB pathways. To our knowledge, this is the first study specifically addressing the impact of the estrous cycle in O3-associated lung inflammatory pathways. | 10.1186/s13293-016-0069-7 |
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