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pubmed_269_17738 | Neuroblastoma is a rare disease. Rare are also the possibilities to test new therapeutic options for neuroblastoma in clinical trials. Despite the constant need to improve therapy and outcomes for patients with advanced neuroblastoma, clinical trials currently only allow for testing few substances in even fewer patients. This increases the need to improve and advance preclinical models for neuroblastoma to preselect favorable candidates for novel therapeutics. Here we propose the use of a new patient-derived 3D slice-culture perfusion-based 3D model in combination with rapid treatment evaluation using isothermal microcalorimetry exemplified with treatment with the novel carbonic anhydrase IX and XII (CAIX/CAXII) inhibitor SLC-0111. Patient samples showed a CAIX expression of 18% and a CAXII expression of 30%. Corresponding with their respective CAIX expression patterns, the viability of SH-EP cells was significantly reduced upon treatment with SLC-0111, while LAN1 cells were not affected. The inhibitory effect on SH-SY5Y cells was dependent on the induction of CAIX expression under hypoxia. These findings corresponded to thermogenesis of the cells. Patient-derived organotypic slice cultures were treated with SLC-0111, which was highly effective despite heterogeneity of CAIX/CAXII expression. Thermogenesis, in congruence with the findings of the histological observations, was significantly reduced in SLC-0111-treated samples. In order to extend the evaluation time, we established a perfusion-based approach for neuroblastoma tissue in a 3D perfusion-based bioreactor system. Using this system, excellent tissue quality with intact tumor cells and stromal structure in neuroblastoma tumors can be maintained for 7 days. The system was successfully used for consecutive drug response monitoring with isothermal microcalorimetry. The described approach for drug testing, relying on an advanced 3D culture system combined with a rapid and highly sensitive metabolic assessment, can facilitate development of personalized treatment strategies for neuroblastoma. | 10.3390/ijms23063128 |
pubmed_916_5806 | A 73-year-old woman had received 9 months of chemotherapy with nab-paclitaxel for locally advanced breast cancer. During the treatment, she was well and showed no major side effects except for alopecia and arthralgia. The tumor showed a tendency to reduction. However, chemotherapy was discontinued because of liver dysfunction. MRCP and ERCP demonstrated multiple stenoses of the hepatic ducts and the intrahepatic bile ducts. We diagnosed chemotherapy-induced sclerosing cholangitis caused by nab-paclitaxel. Treatment with ursodeoxycholic acid and steroid was ineffective. We added bezafibrate, which resulted in a gradual improvement in liver function. To the best of our knowledge, this is the first reported case of nab-paclitaxel-induced secondary sclerosing cholangitis. | 10.11405/nisshoshi.112.888 |
pubmed_978_18717 | To examine the acquisition of voluntary control of a novel muscular activity from the initial stage to the self-control stage, the m. auricularis posterior, which had generally degenerated and had nearly lost its function of drawing an auricle backward in the human body, was selected as a target muscle to be studied. One female undergraduate student who could not move her auricles intentionally was required to activate her left m. auricularis posterior and underwent rest, pretest, training, and posttest sessions once a day for five days. At the subject's request, the electromyograph (EMG) from her left m. auricularis posterior on an oscillograph was provided for her as the feedback signal on each training trial. The picture of her left ear on television was handled in the same way. The EMG measures indicated that the subject could learn to activate her left m. auricularis posterior differentially. The number of training trials on which the subject requested the feedback signals suggested that EMG feedback signal was more useful to her than the video and that the usefulness of the feedback signals varied as the training sessions advanced. It was also concluded from analysis of the self-report data that the acquisition process of self-control of a novel muscular activity could be divided into at least four stages. | 10.2466/pms.1989.69.1.19 |
pubmed_462_20011 | Retinol esterified with long-chain fatty acids is a common dietary source of vitamin A. Hydrolysis of these esters in the lumen of the small intestine is required prior to absorption. Bile salt-stimulated retinyl esterase activity was present with purified rat intestinal brush border membrane, with the maximum rate of ester hydrolysis at approximately pH 8, the physiological luminal pH. Taurocholate, a trihydroxy bile salt, stimulated hydrolysis of short-chain fatty acyl retinyl esters more than hydrolysis of long-chain fatty acyl esters. Deoxycholate, a dihydroxy bile salt, primarily stimulated hydrolysis of long-chain esters. Calculated Kms of 0.74 microM for retinyl palmitate (16:0) hydrolysis and 9.6 microM for retinyl caproate (6:0) hydrolysis suggested the presence of two separate activities. Consistent with that, the activity responsible for retinyl caproate hydrolysis could be inactivated to a greater degree than retinyl palmitate hydrolysis by preincubation of the brush border membrane at 37 degrees C for extended times. Brush border membrane from animals who had undergone common duct ligation 48 h prior to tissue collection showed little ability to hydrolyze retinyl caproate but retained 70% of retinyl palmitate hydrolytic activity, compared to sham-operated controls. Thus, two distinguishable retinyl esterase activities were recovered with purified brush border membranes. One apparently originated from the pancreas, was stimulated by trihydroxy bile salts, and preferentially hydrolyzed short-chain retinyl esters, properties similar to cholesterol ester hydrolase, known to bind to the brush border. The other was intrinsic to the brush border, stimulated by both trihydroxy and dihydroxy bile salts, and preferentially hydrolyzed long-chain retinyl esters, providing the majority of activity of the brush border against dietary retinyl esters. | 10.1021/bi00126a011 |
pubmed_559_14062 | Adults of Cephalonomia stephanoderis Betrem were detected (in November 2003) during the sampling of Coffea canephora Pierre ex A. Froehner berries damaged by Hypothenemus hampei Ferrari (Coleoptera: Scolytidae) in Ouro Preto D'Oeste - Rondônia, Brazil (10 degrees 45'S and 62 degrees 15'W). From January to July 2004, the parasitoid was monthly sampled in 200 berries damaged by H. hampei. Probably, C. stephanoderis can already exert some parasitism pressure at the coffee berry borer population. The occurrence of this parasitoid in natural conditions points out to another alternative for the biological control of the H. hampei in Rondônia. This is the first record of C. stephanoderis in coffee plantations of the Brazilian Amazonia. | 10.1590/s1519-566x2006000400022 |
others_347_10459 | The primary purpose of this investigation was to secure select anatomical and physiological measurements from hypophysectomized rats and their sham-operated control to determine how various endocrine influences could be modified by conditions of simulated microgravity. The focal point of the study was the exercise responses after head-down suspension; however, we were also interested in obtaining insights on nonexercise-related mechanisms. Since more details and information concerning this study will be published elsewhere, we will highlight those findings which warrant further research | others_347_10459 |
others_27_11 | ycatch is the most significant threat to marine megafauna (sea turtles, marine mammals, elasmobranchs, seabirds) worldwide, and the leading cause of the decline of several cetacean species. The bycatch issue in the Indian Ocean is poorly understood, but high bycatch levels in gillnet fisheries have been documented for the past two decades, in both small-scale and semi-industrial fisheries. Unfortunately, methods to reduce bycatch are often unavailable, financially non-viable or socially unacceptable to fishermen. Using a network of trained boat captains in the tuna drift gillnet fishery in the Arabian Sea, targeted catch and bycatch data were collected from 2013 to 2017 off the coast of Pakistan (northern Indian Ocean). Two fishing methods using multifilament gillnets were used: surface deployment and subsurface deployment (i.e. headline of net set below 2 m depth). Predicted catch rates for targeted species did not differ significantly between the two fishing practices, although a drop in tuna (6.2%) and tuna-like (10.9%) species captures was recorded in subsurface sets. The probability of cetacean bycatch, however, was 78.5% lower in subsurface than in surface sets. Cetacean bycatch in tuna drift gillnet fisheries has the potential to be significantly reduced at a relatively low cost for fishers. However, further research with an appropriate sampling design and a large sample size is required to confirm the efficacy of the proposed mitigation method. The acceptability and adoption of subsurface setting by fishers also needs to be further investigated. Despite some limitations, this preliminary study also highlights the importance of crew-based observer data as an alternative source of data when observers cannot be deployed on fishing vessels | 10.1002/aqc.3706 |
pubmed_379_1046 | Unrealistic optimism may contribute to risky health practices and to a delay in seeking treatment for medical conditions, as most individuals perceive themselves to be at little risk for various disorders. It is thus an important concept to present to medical students as part of their behavioural sciences training. Social psychological concepts such as unrealistic optimism may appear, on initial presentation to students, to be a misjudgement based on faulty understanding of risk estimates by the general population. This project aimed to teach the principle of unrealistic optimism by having students document their own beliefs about health risks. Students rated their own risk, relative to other classmates, of experiencing a range of 17 health problems. Questionnaires were completed by two classes of medical students (n = 257). Class results showed varying levels of unrealistic optimism for all 17 conditions. Males and females differed significantly on three of the 17 conditions. Student data were obtained rapidly in a large didactic setting and served to illustrate the concept of unrealistic optimism which was subsequently taught in class. Such exercises may be a useful teaching aid to students providing them with feedback on their own cognitive processes and illustrating that they display cognitive distortions similar to those of patients. | 10.1111/j.1365-2923.1994.tb02728.x |
pubmed_813_10933 | We reviewed cytogenetic studies that have been done in 1,000 consecutive non-oncology samples that were referred to the Cytogenetics Unit at King Khalid University Hospital, Riyadh, Saudi Arabia. The cases were grouped according to the referral diagnosis and the requested cytogenetic service. The frequency of the different types of numerical and structural abnormalities was determined and the relative frequency of cases with abnormal karyotype was calculated in each group. This study should assist physicians in Saudi Arabia and surrounding countries by increasing the awareness of the frequency of cytogenetic abnormality in different diagnostic groups. It also gives figures for comparison with other countries and research centers. | 10.1159/000022877 |
pubmed_803_2099 | Somatic soluble antigens of S. typhi can be subdivided into three categories. These are: 1. Thermolabile antigens (TL) at 100 degrees C or 121 degrees C. They showed two kind of fractions, by immunoelectrophoresis method, some anodic and others cathodic in migration. 2. Thermostable haptens (Th) at 100 degrees C or 121 degrees C. Demonstrated by their capacity to absorb antibodies after heat treatment (100 degrees C or 121 degrees C) and to precipitate antibodies from antiserum produced with unheated bacterial suspensions. These fractions failed to induce antibody production, after heating in rabbits. Electrophoretically they migrated toward the anode. 3. Thermostable antigens (TS) at 100 degrees C or 121 degrees C. Demonstrated by their capacity to induce antibody formation in rabbits after heat treatment at 100 degrees C or 121 degrees C and to precipitate antibodies after being heated at these temperatures. These antigens revealed only cathodic migration. Using the serum made with S. typhi strain Ty-21a, thermolabile and thermostable antigens were demonstrated in S. typhi 0901 strain. | pubmed_803_2099 |
pubmed_138_6465 | In consideration of the fact that the results from the visual appreciation of the fissures in freshly extracted teeth agree with the findings from thin sections of the same teeth, the authors developed a stereomicroscopic method for assessing in vivo the occlusal surfaces of human teeth. The great percentage of accurate assessments of wide fissures obtained with this method permits to recommend it. Narrow fissures may be ascertained by exclusion. | pubmed_138_6465 |
pubmed_672_5389 | 40 patients with spondylolisthesis and/or spondylolysis were studied by magnetic resonance imaging (MR), 12 of whom with correlation to CT. CT proved to be more sensitive in detecting pars defects than MR. Sagittal MR, however, was more accurate in assessing spondylolisthesis than axial CT. At present, CT is superior to MR in demonstrating bony abnormalities. MR appears indicated in the patient undergoing spinal fusion in whom detection of intervertebral disc degeneration in the levels above or below intended fusion may lead to extension of fusion to the degenerated levels. Lack of ionizing radiation makes MR an ideal diagnostic method in evaluating spondylolisthesis in children and adolescents. | 10.1055/s-2008-1044502 |
pubmed_546_16945 | Sound localization in subjects with chronic otitis media (COM) was examined before and soon after ear surgery by means of virtual sound presented by headphones, sound being synthesized based on the head-related transfer functions (HRTFs) in a normal subject. The localization ability in COM patients was usually worse than that in normal subjects, but was better than expected when compared with cases of acute loss. On the other hand, the effects of hearing improvement on localization ability observed in COM patients were smaller than those of simulated acute hearing loss achieved by earplugs in normal subjects. This seems to suggest that the localization cues in patients with chronic hearing loss are different from those under normal conditions. | 10.3109/00206099909073007 |
pubmed_714_15621 | Twenty-five cases of solitary pulmonary chondromatous hamartomas (PCH) were examined by immunohistochemistry to evaluate the mesenchymal and epithelial components. PCH composed of predominantly mature cartilage were designated as C type, those predominantly composed of fibromyxoid tissue as FM type, and those predominantly composed of adipose tissue as A type. FM type PCH revealed various amounts of cartilage in various developmental stages, adipose tissue and fibromyxoid tissue, compared with a uniform pattern of cartilage tissue in C type. The cells of transitional form between spindle cells, stellate cells and chondrocytes were present in FM type. Epithelial components in PCH were bronchial, bronchiolar and cuboidal cells, mostly at the periphery of PCH. S-100 protein consistently stained chondrocytes, stellate and spindle cells in the fibromyxoid tissue of solitary PCH. Fibroblast growth factor was immunolocalized to chondrocytes, spindle and stellate cells in the fibromyxoid tissue. The collagen type was associated with differentiation from primitive mesenchymal cells to chondrocytes (i. e. type I and III collagen appeared in fibromyxoid matrix and type II collagen in the cartilaginous matrix). Fibronectin coordinately appeared with type I and III collagens. The proliferating cell nuclear antigen labeling index of epithelial cells was comparable to those of neoplastic mesenchymal cells, but it was not significantly different between C type and FM type PCH. The primitive mesenchymal cells in the bronchial walls of the control premature neonates were also observed. This immunohistochemical study showed that the progenitor mesenchymal cells in the bronchial and bronchiolar walls may differentiate along chondrocytes, lipocytes, and smooth muscle cells in PCH and that epithelial proliferation is reactive and closely associated with neoplastic proliferation of the mesenchymal component. | 10.1046/j.1440-1827.1999.00969.x |
pubmed_125_25229 | An integrative approach by the congruence of genetics, morphology and ecological niche modelling (ENM) was used to delimit a new species of Hypanus (Rafinesque, 1818), a recently resurrected genus of marine stingrays comprising eight species, five of which occur in the western Atlantic. The species with the widest distribution, Hypanus americanus (Hildebrand and Schroeder, 1928), from the northeastern coast of the United States to southeastern Brazil, was demonstrated to be paraphyletic based on protein-coding mitochondrial genome analyses. This data set also indicates that the genetic distance between the new species Hypanus berthalutzae sp. nov. and its three closely related species (H. americanus, H. longus and H. rudis) varies from 0.82% to 3.14%. In addition, Bayesian Analysis of Population Similarity using the mitochondrial gene mt-nd2 supports the separation of H. berthalutzae sp. nov. (southwestern Atlantic) from its sister species H. rudis (eastern Atlantic). Similarly, morphological and morphometric analyses corroborated four morphotypes within the H. americanus species group and indicated the ventral caudal fold height and length and interspiracular and interorbital lengths as useful measurements to distinguish among them. Claspers of adult males also exhibit morphological differences among species. The ENM agreed with molecular and morphological analyses and delimits the distribution of H. berthalutzae sp. nov. to shallow areas close to shore along the Brazilian coast, from the mouth of the Amazon River to São Paulo State, including the northeastern oceanic islands, suggesting that the great outflow of fresh water and sediments and the Mid-Atlantic Ridge might act as barriers. The integration of these data to describe a new species provides information relevant to their conservation status, because all species of the H. americanus species group are under the "data-deficient" status. | 10.1111/jfb.14483 |
pubmed_1025_473 | The current study investigated the contributions of contralesional primary somatosensory cortex (S1c) to motor learning deficits post-stroke. For three days, continuous theta burst (cTBS) was delivered over the contralesional hemisphere prior to practicing a serial targeting task. cTBS was delivered over either S1c, contralesional primary motor cortex (M1c) or as control stimulation (n=4/group). Change in motor ability was assessed from initial performance to a delayed retention test using a serial targeting task and a subset of items from the Wolf Motor Function Test. Practice preceded by cTBS over either M1c or S1c resulted in large decreases in movement time compared to practice preceded by control stimulation. M1c cTBS resulted in larger decreases in peak velocity and peak acceleration compared to control and S1c cTBS. In contrast, S1c cTBS resulted in larger reductions in time to initiate movement and time to complete the WMFT compared to control and M1c cTBS. These preliminary findings suggest that stimulation of either M1c or S1c can enhance the benefits of practice. However, changes in M1c and S1c excitability may contribute to different aspects of post-stroke motor deficits that may differentially impact rehabilitation. | 10.1016/j.neulet.2011.05.237 |
pubmed_448_16548 | BACKGROUND
Current studies in patients with congenital muscular torticollis (CMT) have predominantly focused on the role of tuina or paraffin therapy alone. This systematic review with Bayesian network meta-analysis will be performed to sum up the existing evidence on the effects and safety of tuina plus paraffin therapy for CMT in infants and children.
METHODS
The Preferred Reporting Items for Systematic Reviews and Meta-Analyzes reporting guidelines will be followed to conduct this study. The electronic databases of PubMed, Cochrane Library, PsycINFO, EMBASE, the Chinese Scientific Journal Database, China National Knowledge Infrastructure, WanFang Data, Taiwan Electronic Periodical Services, and Web of Science will be searched from the inception to November 2021 using the following key terms: "Tuina," "traditional Chinese medicine massage," "paraffin," and "congenital muscular torticollis," for all relevant studies. We impose no language restrictions. We include reports on randomized controlled trials (RCTs) and quasi-RCTs of Tuina combline with paraffin therapy for the treatment of CMT in children and adolescents. We include studies that assessed effective rate, symmetry, improvements of range of motion, muscle length, and sternocleidomastoid tumor thickness, quality of life, and adverse events. The Cochrane Bias Risk Tool, which considers sequence generation, allocation concealment, and blinding and other aspects of bias, will be used to assess the risk of bias in studies.
RESULTS
A Bayesian network meta-analysis is an appropriate statistical method to compare all treatment options by statistically simulating the estimated results of a comprehensive trial, and to compare treatments by common and associated comparators. In addition, Bayesian network meta-analysis can produce ranking probabilities of treatments, which may contribute to clinicians' clinical decision-making.
REGISTRATION NUMBER
10.17605/OSF.IO/K5EGN. | 10.1097/MD.0000000000027648 |
pubmed_934_18091 | This pilot study evaluated the predictive value of flow-mediated dilation (FMD) for damage accrual in a cohort of SLE patients. Thirty-eight female SLE patients without cardiovascular involvement were enrolled. Clinical history, traditional cardiovascular risk factors, laboratory parameters, disease activity and damage and brachial artery FMD were collected at study entry and after a mean follow-up of 4.5 years. At enrollment, 18 patients (47%) presented active disease; mean FMD was 7.9 ± 3.1%, with no statistically significant differences between women with active and inactive disease. During the follow-up, 3 patients died and 14 accrued organ damage. Baseline FMD did not predict death and damage accrual. FMD showed significant decline over time, which was greater in patients with poor outcome (-3.9% vs -1.9%, p = 0.03). In conclusion, in a cohort of SLE patients, baseline FMD was not predictive of damage accrual. However, the latter was associated with progressive loss of FMD. | pubmed_934_18091 |
pubmed_425_17331 | Down syndrome cell adhesion molecules (dscam and dscaml1) are essential regulators of neural circuit assembly, but their roles in vertebrate neural circuit function are still mostly unexplored. We investigated the functional consequences of dscaml1 deficiency in the larval zebrafish (sexually undifferentiated) oculomotor system, where behavior, circuit function, and neuronal activity can be precisely quantified. Genetic perturbation of dscaml1 resulted in deficits in retinal patterning and light adaptation, consistent with its known roles in mammals. Oculomotor analyses revealed specific deficits related to the dscaml1 mutation, including severe fatigue during gaze stabilization, reduced saccade amplitude and velocity in the light, greater disconjugacy, and impaired fixation. Two-photon calcium imaging of abducens neurons in control and dscaml1 mutant animals confirmed deficits in saccade-command signals (indicative of an impairment in the saccadic premotor pathway), whereas abducens activation by the pretectum-vestibular pathway was not affected. Together, we show that loss of dscaml1 resulted in impairments in specific oculomotor circuits, providing a new animal model to investigate the development of oculomotor premotor pathways and their associated human ocular disorders.SIGNIFICANCE STATEMENTDscaml1 is a neural developmental gene with unknown behavioral significance. Using the zebrafish model, this study shows that dscaml1 mutants have a host of oculomotor (eye movement) deficits. Notably, the oculomotor phenotypes in dscaml1 mutants are reminiscent of human ocular motor apraxia, a neurodevelopmental disorder characterized by reduced saccade amplitude and gaze stabilization deficits. Population-level recording of neuronal activity further revealed potential subcircuit-specific requirements for dscaml1 during oculomotor behavior. These findings underscore the importance of dscaml1 in the development of visuomotor function and characterize a new model to investigate potential circuit deficits underlying human oculomotor disorders. | 10.1523/JNEUROSCI.1783-19.2019 |
pubmed_939_25822 | Closed-head trauma is a well-recognized etiology of acquired superior oblique (SO) palsy. However, combined SO palsy and ipsilateral Brown's syndrome after a closed-head trauma is rare. We describe a patient with this ocular motility disorder and conduct a brief review of the literature. | 10.4103/tjo.tjo_130_18 |
pubmed_292_4153 | Recent studies have shown that polymorphisms in leptin and leptin receptor genes are associated with increased risk for breast cancer. This study aimed at investigating -2548 G/A polymorphism in leptin gene and Q223R polymorphism in leptin receptor gene in patients with breast cancer. The study included 45 women with breast cancer and 41 healthy women. PCR-RFLP was used to determine the genotype of the subjects in terms of -2548 G/A polymorphism in leptin gene and Q223R polymorphism in leptin receptor gene. Serum levels of leptin were also measured by ELISA. For -2548 G/A polymorphism, the genotypes were homozygous AA (OR = 1.13; p = 0.8) and heterozygous GA (OR = 0.41; p = 0.2) and for Q223R polymorphism, the genotypes were homozygous RR (OR = 6.7; p = 0.09) and heterozygous QR (OR = 8.3; p = 0.06). The mean serum level of leptin was 33.22 ± 21.35 ng/mL in patients and 29.49 ± 23.27 ng/mL in the normal participants (p = 0.3). Although, despite the magnitude of the associations, the results suggested no statistically significant contribution of -2548 G/A polymorphism (in leptin gene), Q223R polymorphism (in leptin receptor gene), and serum leptin levels in predicting the risk of breast cancer, further studies with larger sample size are suggested. | 10.1155/2015/132720 |
pubmed_283_7234 | Activation of complement components is crucial in the progression and severity of myasthenia gravis and experimental autoimmune myasthenia gravis (EAMG). Mice deficient in complement component C4 or treated with monoclonal antibody to C1q are resistant to EAMG. In this study, we show that inhibition of complement cascade activation by suppressing the expression of a critical low-abundant protein, C2, in the classical complement pathway, significantly improved clinical and immunopathological manifestations of EAMG. Two weeks after a second booster immunization with acetylcholine receptor, when mice exhibit muscle weakness, i.p. injection of C2 siRNA significantly suppressed C2 mRNA in the blood cells and liver of EAMG mice. Treatment of EAMG mice with C2 siRNA, once a week for 5 weeks, significantly improved muscle strength, which was further evidenced by functional AChR preservation in muscle, reduction in number of C3 and membrane-attack complexes at neuro-muscular junctions in forelimb muscle sections, and a transient decrease in serum IgG2b levels. Our study shows for the first time that siRNA-mediated suppression of C2, a component of the classical complement system, following established disease, can effectively contribute to the remission of EAMG. Therefore, C2 siRNA mediated therapy can be applied in all complement mediated autoimmune diseases. | pubmed_283_7234 |
pubmed_1077_7606 | Late-onset hypogonadism is defined as a combination of low testosterone (T) levels and typical symptoms and signs. A major area of uncertainty is whether T concentrations are always really sufficient to fully reflect Leydig cell (dys)function. Mild testicular alteration could be diagnosed only by additional biochemical markers, such as luteinizing hormone (LH) and 25-hydroxyvitamin D levels. These markers help in identifying the so-called "subclinical" hypogonadism (normal T, high LH levels). Patients with hypogonadism have frequently low levels of 25-hydroxyvitamin D due to impairment of the hydroxylating enzyme CYP2R1 in the testis. However, no data have been published dealing with the best treatment option (cholecalciferol - the Vitamin D precursor, or calcidiol - 25-hydroxylated form of Vitamin D) in these patients. We studied 66 patients with classic hypogonadism (total T [TT] <12 nmol l-1 , LH ≥ 8 IU l-1 ) (n = 26) and subclinical hypogonadism (TT ≥ 12 nmol l-1 , LH ≥ 8 IU l-1 ) (n = 40) and low 25-hydroxyvitamin D (<50 nmol l-1 ). Subjects received cholecalciferol (5000 IU per week) (n = 20) or calcidiol (4000 IU per week) (n = 46), and 25-hydroxyvitamin D and parathyroid hormone (PTH) were evaluated after 3 months of therapy. Supplementation with calcidiol significantly increased 25-hydroxyvitamin D and significantly decreased PTH levels in both groups of men with hypogonadism (primary, n = 16 and subclinical, n = 30), whereas supplementation with cholecalciferol did not modify their levels. This study shows for the first time that the administration of the 25-hydroxylated form of Vitamin D (calcidiol), and not the administration of the precursor cholecalciferol, restores 25-hydroxyvitamin D levels in subjects with hypogonadism. | 10.4103/1008-682X.135985 |
pubmed_764_5231 | Scorpion venom can induce in dogs severe haemodynamic changes leading to rapid rise in systemic blood pressure and cardiac output, followed by reduction of cardiac output and blood pressure within 1 h. The decrease in cardiac output is not related to myocardial dysfunction (Tarasiuk et al. 1994). We hypothesized that scorpion venom affects cardiac output by reducing venous return to the heart. Venous return was studied by steady-state measurements of cardiac output, the pressure gradient and resistance to venous return, in 16 dogs following injection of 0.05 mg kg-1 venom obtained from the scorpion species Leiurus quinquestriatus. In eight of the 16 dogs, atropine (0.1 mg kg-1) was given 15 min prior to venom injection (n = 4) or 85 min (n = 4) after venom administration. In five additional dogs, the stability of the preparation over time was evaluated following the same protocol without the injection of the venom. At 15 min, the venom induced an increase in blood pressure (80%) and cardiac output (250%) (P < 0.001) with little effect on heart rate. At 90 min, cardiac output and heart rate declined considerably below baseline (P < 0.001). Atropine prevented the decrease in heart rate, but did not affect the reduction of cardiac output. Five minutes after venom injection, mean circulatory pressure increased by 300% (P < 0.001), which was accompanied by a rightward shift of the venous return curve with no effect on resistance to venous return. At 120 min, mean circulatory pressure recovered and resistance to venous return remained at 40% (P < 0.01) above baseline. This study indicates that, in dogs, scorpion venom affects cardiac output by modifying the determinants of venous return. The initial increase in cardiac output is related to increased mean circulatory pressure since resistance to venous return did not change. The later fall in cardiac output is related to the reduction of mean circulatory pressure and increased resistance to venous return. | 10.1046/j.1365-201X.1997.00202.x |
pubmed_147_6823 | The plasma free amino acid (PFAA) profile is affected by various nutritional conditions, such as the dietary energy balance. Regarding the clinical use of PFAA profiling, it is of concern that differences in food ingestion patterns may generate systematic errors in a plasma amino acid profile and constitute a confounding factor in assessment. In this study, the overnight impact of the dietary energy balance on the postprandial plasma amino acid profile was investigated to elucidate in particular the effects of high protein meals typical in Japanese cuisine. We conducted diet-controlled, crossover trials in eleven healthy male volunteers aged 40-61 y. They consumed either a normal meal (meal N) or high protein meal (meal H) at dinner. Forearm venous blood was collected, and plasma amino acid concentrations were measured before dinner and the next morning. We found that a high protein meal in the evening that contained 40% energy would significantly increase the PFAA concentration the next morning, even more than 12 hours after the meal. Among amino acids, the most significant difference was observed in the branched-chain amino acids (BCAAs) and in some urea-cycle related compounds. If the subject consumed the high protein diet at dinner, the PFAA profile after overnight fasting might be still affected by the meal even 12 hours after the meal, suggesting that the PFAA profile does not reflect the subject's health condition, but rather the acute effect of high protein ingestion. | 10.1371/journal.pone.0062929 |
pubmed_123_12176 | Insulin stimulates glucose transport in muscle and adipose tissue by triggering the movement of the glucose transporter GLUT-4 from an intracellular compartment to the cell surface. Fundamental to this process is the intracellular sequestration of GLUT-4 in nonstimulated cells. Two distinct targeting motifs in the amino and carboxy termini of GLUT-4 have been previously identified by expressing chimeras comprised of portions of GLUT-4 and GLUT-1, a transporter isoform that is constitutively targeted to the cell surface, in heterologous cells. These motifs-FQQI in the NH2 terminus and LL in the COOH terminus-resemble endocytic signals that have been described in other proteins. In the present study we have investigated the roles of these motifs in GLUT-4 targeting in insulin-sensitive cells. Epitope-tagged GLUT-4 constructs engineered to differentiate between endogenous and transfected GLUT-4 were stably expressed in 3T3-L1 adipocytes. Targeting was assessed in cells incubated in the presence or absence of insulin by subcellular fractionation. The targeting of epitope-tagged GLUT-4 was indistinguishable from endogenous GLUT-4. Mutation of the FQQI motif (F5 to A5) caused GLUT-4 to constitutively accumulate at the cell surface regardless of expression level. Mutation of the dileucine motif (L489L490 to A489A490) caused an increase in cell surface distribution only at higher levels of expression, but the overall cells surface distribution of this mutant was less than that of the amino-terminal mutants. Both NH2- and COOH-terminal mutants retained insulin-dependent movement from an intracellular to a cell surface locale, suggesting that neither of these motifs is involved in the insulin-dependent redistribution of GLUT-4. We conclude that the phenylalanine-based NH2-terminal and the dileucine-based COOH-terminal motifs play important and distinct roles in GLUT-4 targeting in 3T3-L1 adipocytes. | 10.1083/jcb.130.5.1081 |
pubmed_460_14652 | The SMARCA4/BRG1 gene product is a component of the SWI-SNF chromatin-remodeling complex and regulates gene expression by disrupting histone-DNA contacts in an ATP-dependent manner. Inactivating mutations of the SMARCA4 gene, on chromosome arm 19p, are present in several human cancer cell lines, including cell lines derived from lung cancers. Interestingly, loss of heterozygosity (LOH) at 19p and absence of the SMARCA4 protein have been reported in lung tumors. To evaluate further the possible contribution of SMARCA4 gene inactivation to lung carcinogenesis, we performed a complete analysis of the SMARCA4 gene to search for (a) point mutations in all 35 coding exons, including an existing splicing variant and the intron-exon boundaries, and (b) abrogation of gene expression through promoter hypermethylation by using the methylation-specific polymerase chain reaction (MSP) assay. We selected genomic DNA from 20 lung primary tumors with LOH on 19p for the screening of point mutations and 10 lung cancer cell lines and 52 lung primary tumors for the MSP analysis. Through our mutational screening, we identified an in-frame and germ-line insertion of 24 bp in exon 4 whose biological relevance is unknown. This variant was not detected in the germ line of the 62 additional individuals analyzed, indicating it is not a common polymorphism. Moreover, two missense alterations were identified in the tumors of 2 patients, a somatic Gly1160Arg mutation and a Ser1176Cys mutation. Neither was present in the germ line of the 51 additional lung cancer individuals tested. Because these mutations lead to substitution of highly conserved amino acids, they may affect the ATPase function of the protein. Finally, no promoter hypermethylation was observed in any lung primary tumor or cancer cell line, indicating that this is not a major mechanism for SMARCA4 inactivation during lung carcinogenesis. In conclusion, our data revealed that somatic point mutations of the SMARCA4 gene are present in a small subset of lung tumors, although mutations affecting the ATPase domain may be a hot-spot for SMARCA4 gene inactivation. We cannot rule out that other mechanisms, such as complete or partial deletions of the SMARCA4 gene, are contributing to the loss of the SMARCA4 protein in lung cancer. | 10.1002/gcc.20068 |
pubmed_964_5424 | The key to technologic assessment of the chest pain unit lies in the recognition of the unit's ability to optimize outcomes of an illness with high incidence, high acute mortality and significant chronic morbidity. The chest pain observation unit, as an adjunct to the emergency department (ED), offers health managers and administrators the clinical tool, first envisioned by Dr. Lown in the 1960s, to achieve improved quality and cost-effectiveness of acute chest pain management as health care moves into a new century. | pubmed_964_5424 |
pubmed_9_7316 | A rapid method of performing the Limulus amoebocyte lysate (LAL) test in milk is proposed using the Toxinometer ET-201. This instrument measured the increase in turbidity due to the interaction between the endotoxins of the Gram-negative bacteria and the LAL reagent, monitored the ratio Rt of the sequential to the initial transmission at 12 s intervals and quantified endotoxins by determination of the reaction time Tr required to obtain a 5% decrease in Rt. There was a good correlation between the toxinometrically determined endotoxin concentrations and the number of Gram-negative bacteria (SD, 0.18 log(plate count units)), and the repeatability (CV, 6-10%) was high. The assay may be useful for screening raw materials for UHT milk production, as the endotoxin content of the raw material is related to the rest proteinase activity in the UHT milk. | 10.1017/s0022029900027539 |
pubmed_616_2593 | Acute coronary syndrome (ACS) is a common disease with high mortality and morbidity rates. The methylation status of blood DNA may serve as a potential early diagnosis and prevention biomarker for numerous diseases. The present study was designed to explore novel genome-wide aberrant DNA methylation patterns associated with ACS. The Infinium HumanMethylation450 assay was used to examine genome-wide DNA methylation profiles in 3 pairs of ACS and control group samples. Epigenome-wide DNA methylation, genomic distribution, Gene Ontology (GO) term and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed. The results were confirmed using methylation-specific polymerase chain reaction (MSP) and Sequenom MassARRAY analyses in ACS, stable coronary artery disease (SCAD) and control samples. A total of 11,342 differentially methylated (DM) 5'-C-phosphate-G-3' (CpG) sites were identified, including 8,865 hypomethylated and 2,477 hypermethylated CpG sites in the ACS group compared with the control samples. They varied in frequency across genomic compartments, but were particularly notable in gene bodies and shores. The results of GO term and KEGG pathway enrichment analyses revealed that the methylated genes were associated with certain biological processes and pathways. Despite the considerable variability in methylation data, the candidate selected possessed significant methylation alteration in mothers against decapentaplegic homolog 3 (SMAD3) transcription start site 155 (Chr1:67356838-Chr1:67356942). MSP analysis from 81 ACS samples, 74 SCAD samples and 53 healthy samples, and Sequenom MassARRAY analysis, confirmed that differential CpG methylation of SMAD3 was significantly corrected with the reference results of the HumanMethylation450 array. The data identified an ACS-specific DNA methylation profile with a large number of novel DM CpG sites, some of which may serve as candidate markers for the early diagnosis of ACS. | 10.3892/ijmm.2017.3220 |
pubmed_656_24852 | Visualizing spatial data on small-screen devices such as smartphones and smartwatches poses new challenges in computational cartography. The current interfaces for map exploration require their users to zoom in and out frequently. Indeed, zooming and panning are tools suitable for choosing the map extent corresponding to an area of interest. They are not as suitable, however, for resolving the graphical clutter caused by a high feature density since zooming in to a large map scale leads to a loss of context. Therefore, in this paper, we present new external labeling methods that allow a user to navigate through dense sets of points of interest while keeping the current map extent fixed. We provide a unified model, in which labels are placed at the boundary of the map and visually associated with the corresponding features via connecting lines, which are called leaders. Since the screen space is limited, labeling all features at the same time is impractical. Therefore, at any time, we label a subset of the features. We offer interaction techniques to change the current selection of features systematically and, thus, give the user access to all features. We distinguish three methods, which allow the user either to slide the labels along the bottom side of the map or to browse the labels based on pages or stacks. We present a generic algorithmic framework that provides us with the possibility of expressing the different variants of interaction techniques as optimization problems in a unified way. We propose both exact algorithms and fast and simple heuristics that solve the optimization problems taking into account different criteria such as the ranking of the labels, the total leader length as well as the distance between leaders. In experiments on real-world data we evaluate these algorithms and discuss the three variants with respect to their strengths and weaknesses proving the flexibility of the presented algorithmic framework. | 10.1109/TVCG.2020.3030399 |
pubmed_401_17707 | Rabies is a fatal aggressive disease of the nervous system which predominantly causes motor and autonomic dysfunction. Limbic system involvement has been reported rarely, with limited data on its prevalence. The diagnosis becomes challenging when a patient presents with limbic system involvement in the absence of a clear history of an animal bite. We herein illustrate a case of a young man who presented with recurrent episodes of inappropriate ejaculation. He eventually developed hydrophobia and aerophobia, leading to a diagnosis of rabies. This case emphasises the importance of considering the possibility of rabies encephalitis when a patient presents with symptoms of limbic system involvement since early diagnosis helps in instituting appropriate public health measures and reducing exposure to infection. Furthermore, high-quality intensive care with supportive management is the mainstay of therapy in such patients until we have novel and effective antiviral drugs for rabies treatment. | 10.1136/bcr-2022-249965 |
pubmed_980_19941 | Importance
The decision to proceed with tonsillectomy to treat pediatric obstructive sleep-disordered breathing (OSDB) often falls on individual families. Despite emphasis on shared decision-making between parents and surgeons about tonsillectomy for OSDB, the extent to which parents have already decided about surgery prior to the child's consultation is not known.
Objective
To identify predictors of parent choice predisposition for surgical treatment of OSDB with tonsillectomy and describe its association with parent-clinician communication.
Design, Setting, and Participants
Observational cohort study conducted at 3 outpatient clinical sites (urban-based outpatient center, suburban off-site outpatient center, and community-based medical center) associated with a large academic center. A total of 149 parents of children undergoing their initial otolaryngology consultation for OSDB were identified through clinic scheduling records and deemed eligible for participation in this study. Of the 149 parents, a volunteer sample of 64 parents (42.9%) agreed to participate and have their consultation audiorecorded. Of these 64 participants, 12 parents were excluded because their child had previously been evaluated for OSDB by a specialist.
Main Outcomes and Measures
The primary outcomes and measures were treatment choice predisposition scale (a measure of the strength of a patient's treatment decision prior to entering a medical consultation), parent communication behaviors coded in consultation audiorecordings (substantive questions asked, introduced medical jargon, expression of treatment preference, and scores on the OSDB and Adenotonsillectomy Knowledge Scale for parents).
Results
A total of 52 parent participants were included in the final analysis. Most parent participants were female (n = 48; 92%); 50% (n = 26) of parents were non-Hispanic White, 37% (n = 19) were Black, 10% (n = 5) were Hispanic/Latino, and 4% (n = 2) self-reported race/ethnicity as "Other." Mean (range) choice predisposition was 6.84 (2-10), with 22 parents (42%) more predisposed to choose tonsillectomy. Parents more predisposed to choose tonsillectomy used more medical jargon during the consultation (odds ratio [OR], 3.95; 95% CI, 1.16-15.15) and were less likely to ask questions (OR, 0.22; 95% CI, 0.05-0.87). Parental predictors of greater predisposition toward choosing surgery were White race (OR, 7.31; 95% CI, 1.77-39.33) and prior evaluation by a pediatrician for OSDB (OR, 6.10; 95% CI, 1.44-33.34).
Conclusions and Relevance
In this cohort study of parents of children with OSDB, many parents were predisposed to choose treatment with tonsillectomy prior to initial surgical consultation, which may lessen engagement and influence 2-way communication. In this cohort, greater predisposition for tonsillectomy was observed in non-Hispanic White parents and parents of patients who had been previously evaluated by a pediatrician for OSDB. Understanding parent choice predisposition for surgery may promote improved communication and parental engagement during surgical consultations. It may also help direct education about sleep and tonsillectomy to nonsurgical forums. | 10.1001/jamaoto.2020.5031 |
pubmed_275_10816 | BACKGROUND AND OBJECTIVES
In countries with a high frequency of tuberculosis, there are problems not only with active lung tuberculosis but also with past lung tuberculosis. Cases with sequel tuberculosis very frequently present with complaints like tuberculosis, and it is very hard to determine whether it is a sequel tuberculosis complication or reactivation of tuberculosis. In this study, we measured the serum reactive oxygen metabolite (ROM) levels of patients with active pulmonary tuberculosis and healthy controls, and investigated if these metabolites can be used as a criterion for differentiation between active pulmonary tuberculosis and sequel pulmonary tuberculosis.
METHODS
40 patients with active tuberculosis, 35 patients with sequel pulmonary tuberculosis and 30 healthy control subjects with a similar age range and sex distribution were included in the study. Serum total ROM levels were detected in the patients and control group.
RESULTS
Mean serum ROM values were 994+/-236, 551+/-135 and 236+/-59 U/l among active lung tuberculosis cases, sequel lung tuberculosis cases and the healthy control group, respectively. As a result of these findings, serum ROM levels of active lung tuberculosis cases and sequel lung tuberculosis cases were significantly higher than those of the control group (both p<0.001). The serum ROM levels of active lung tuberculosis cases were also significantly higher than those of sequel lung tuberculosis cases (p<0.001).
CONCLUSIONS
In the light of our findings, it may be assumed that serum total ROM values can be used as an activity criterion in the differentiation of active lung tuberculosis and sequel lung tuberculosis. | 10.1159/000084046 |
pubmed_35_9111 | Admixture between populations originating on different continents can be exploited to detect disease susceptibility loci at which risk alleles are distributed differentially between these populations. We first examine the statistical power and mapping resolution of this approach in the limiting situation in which gamete admixture and locus ancestry are measured without uncertainty. We show that, for a rare disease, the most efficient design is to study affected individuals only. In a typical African American population (two-way admixture proportions 0.8/0.2, ancestry crossover rate 2 per 100 cM), a study of 800 affected individuals has 90% power to detect at P values <10(-5) a locus that generates a risk ratio of 2 between populations, with an expected mapping resolution (size of 95% confidence region for the position of the locus) of 4 cM. In practice, to infer locus ancestry from marker data requires Bayesian computationally intensive methods, as implemented in the program ADMIXMAP. Affected-only study designs require strong prior information on the frequencies of each allele given locus ancestry. We show how data from unadmixed and admixed populations can be combined to estimate these ancestry-specific allele frequencies within the admixed population under study, allowing for variation between allele frequencies in unadmixed and admixed populations. Using simulated data based on the genetic structure of the African American population, we show that 60% of information can be extracted in a test for linkage using markers with an ancestry information content of 36% at 3-cM spacing. As in classic linkage studies, the most efficient strategy is to use markers at a moderate density for an initial genome search and then to saturate regions of putative linkage with additional markers, to extract nearly all information about locus ancestry. | 10.1086/420855 |
pubmed_962_698 | Since the record impact of Hurricane Katrina, attention has focused on understanding trends in hurricanes and their destructive potential. Emanuel reports a marked increase in the potential destructiveness of hurricanes based on identification of a trend in an accumulated annual index of power dissipation in the North Atlantic and western North Pacific since the 1970s. If hurricanes are indeed becoming more destructive over time, then this trend should manifest itself in more destruction. However, my analysis of a long-term data set of hurricane losses in the United States shows no upward trend once the data are normalized to remove the effects of societal changes. | 10.1038/nature04426 |
pubmed_988_4950 | Thirty-six thousand two hundred fifty abdominal hernia repairs were performed in U.S. Army medical treatment facilities during a five-year period. This study presents data about the type of hernia, incidence of complications by obstruction or strangulation, age, sex, and mortality. Hernias occurring with intestinal obstruction or gangrene (strangulation) are referred to as complicated hernias. Inguinal hernias in children less than two years of age, femoral hernias, and unusual (such as internal or obturator) hernias were found to have an increased incidence of complications. Surgical repair of ventral, umbilical, and femoral hernias was done with a low surgical risk and the presence of complications did not significantly increase this risk. An increased risk of mortality is associated with the repair of complicated unusual hernias and complicated inguinal hernias in patients more than 60 years of age. | pubmed_988_4950 |
pubmed_734_3954 | OBJECTIVE
To develop and validate an accurate, usable prediction model for other-cause mortality (OCM) in patients with prostate cancer diagnosed in the United States.
MATERIALS AND METHODS
Model training was performed using the National Health and Nutrition Examination Survey 1999-2010 including men aged >40 years with follow-up to the year 2014. The model was validated in the Prostate, Lung, Colon, and Ovarian Cancer Screening Trial prostate cancer cohort, which enrolled patients between 1993 and 2001 with follow-up to the year 2015. Time-dependent area under the curve (AUC) and calibration were assessed in the validation cohort. Analyses were performed to assess algorithmic bias.
RESULTS
The 2420 patient training cohort had 459 deaths over a median follow-up of 8.8 years among survivors. The final model included eight predictors: age; education; marital status; diabetes; hypertension; stroke; body mass index; and smoking. It had an AUC of 0.75 at 10 years for predicting OCM in the validation cohort of 8220 patients. The final model significantly outperformed the Social Security Administration life tables and showed adequate predictive performance across race, educational attainment, and marital status subgroups. There is evidence of major variability in life expectancy that is not captured by age, with life expectancy predictions differing by 10 or more years among patients of the same age.
CONCLUSION
Using two national cohorts, we have developed and validated a simple and useful prediction model for OCM for patients with prostate cancer treated in the United States, which will allow for more personalized treatment in accordance with guidelines. | 10.1111/bju.15740 |
pubmed_383_22194 | Current therapeutic strategies such as angiogenic therapy and anti-inflammatory therapy for treating myocardial infarction have limited success. An effective approach may benefit from resolution of excessive inflammation combined with enhancement of angiogenesis. Here, we developed a microRNA-21-5p delivery system using functionalized mesoporous silica nanoparticles (MSNs) with additional intrinsic therapeutic effects. These nanocarriers were encapsulated into an injectable hydrogel matrix (Gel@MSN/miR-21-5p) to enable controlled on-demand microRNA-21 delivery triggered by the local acidic microenvironment. In a porcine model of myocardial infarction, we demonstrated that the released MSN complexes notably inhibited the inflammatory response by inhibiting the polarization of M1 macrophage within the infarcted myocardium, while further microRNA-21-5p delivery by MSNs to endothelial cells markedly promoted local neovascularization and rescued at-risk cardiomyocytes. The synergy of anti-inflammatory and proangiogenic effects effectively reduced infarct size in a porcine model of myocardial infarction. | 10.1126/sciadv.abd6740 |
pubmed_212_3881 | Nucleic acid synthesis and influence of cytostatic agents (adriamycin, cyclophosphamide) were investigated in 73 cases of human breast cancer and in 19 cases of correlating lymph node metastases. An interrelationship between nucleic acid synthesis, proliferation and tumor stage could not be proven at the time of the operation. The labeling index, expressing the proliferation of tumor cells, and the incorporation of radiolabeled nucleic acid precursors (3H-thymidine, 3H-uridine) as an indicator of nucleic acid synthesis were higher in the investigated lymph node metastases than in the primary tumor. Nucleic acid synthesis was suppressed in primary and metastatic lesions in the same way by cytostatic agents. | pubmed_212_3881 |
pubmed_69_1841 | BACKGROUND
It has been suggested that dust exposure causes airway inflammation among cement factory workers. However, there is limited information on the mechanisms of this effect. We explored any associations between total dust exposure and fractional exhaled nitric oxide (FENO) as a marker of airway eosinophilic inflammation among cement production workers in Tanzania. We also examined possible differences in FENO concentration between workers in different parts of the production line.
METHODOLOGY
We examined 127 cement workers and 28 controls from a mineral water factory. An electrochemistry-based NIOX MINO device was used to examine FENO concentration. Personal total dust was collected from the breathing zone of the study participants using 37 mm cellulose acetate filters placed in three-piece plastic cassettes. Interviews on workers' background information were conducted in the Swahili language.
RESULTS
We found equal concentrations of FENO among exposed workers and controls (geometric mean (GM)=16 ppb). The GM for total dust among the exposed workers and controls was 5.0 and 0.6 mg/m(3), respectively. The FENO concentrations did not differ between the exposed workers with high (GM≥5 mg/m(3)) and low (GM<5 mg/m(3)) total dust exposure. There was no significant difference in FENO concentration between workers in the two main stages of the cement production process.
CONCLUSIONS
We did not find any difference in FENO concentration between dust-exposed cement workers and controls, and there were similar FENO concentrations among workers in the two main stages of cement production. | 10.1136/oemed-2012-100879 |
pubmed_1008_10348 | Myelomeningoceles underlie critical indication for surgical closure. Clearcut contra indications such as total congenital hydrocephalus, intracranial haemorrhage and cerebral bith-traumatic lesions, severe forms of gibbus and the combination with other severe malformations eliminate the right of active surgery. The conservative treatment neither corresponds to therapeutic nihilism nor is it the inevitability of a lethal outcome. The author does not agree with conceptions such as selection of criteria of selection according to Lorber. | pubmed_1008_10348 |
pubmed_621_8212 | PURPOSE
Active Ageing (AA), as described by the WHO (Active Ageing: a policy framework. World Health Organisation, Geneva 5), is an important concept in gerontology. Since the AA-concept has not been examined in the context of residential long-term care facilities, our study addresses this gap by describing the determinants of AA within this setting.
METHODS
A qualitative study with semi-structured focus groups, followed by a thematic analysis, was conducted. Through purposive sampling, four focus groups of either residents of long-term care facilities (n = 8), children of residents (n = 8), community-dwelling older people (n = 8) and gerontologists (n = 6) were formed.
RESULTS
The thematic analysis yielded nine determinants of AA. Seven correspond to those identified by the WHO: Culture, Behaviour, Psychological Factors, Physical Environment, Social Environment, Economic Characteristics and Health and Social Care. Two new determinants were identified: Meaningful Leisure and Participation. The determinant Participation is seen as crucial to AA in residential care.
CONCLUSION
This study points to a more extensive set of determinants of AA than those identified by the WHO (Active Ageing: a policy framework. World Health Organisation, Geneva 5). Staff of long-term care facilities can make use of these determinants to promote AA in their residents. | 10.1007/s11136-012-0216-5 |
pubmed_400_7318 | Mammalian target of rapamycin (mTOR) is the central element of a signaling pathway involved in the control of mRNA translation and cell growth. The actions of mTOR are mediated in part through the phosphorylation of the eukaryotic initiation factor 4E-binding protein, PHAS-I. In vitro mTOR phosphorylates PHAS-I in sites that control PHAS-I binding to eukaryotic initiation factor 4E; however, whether mTOR directly phosphorylates PHAS-I in cells has been a point of debate. The Arg-Ala-Ile-Pro (RAIP motif) and Phe-Glu-Met-Asp-Ile (tor signaling motif) sequences found in the NH2- and COOH-terminal regions of PHAS-I, respectively, are required for the efficient phosphorylation of PHAS-I in cells. Here we show that mutations in either motif markedly decreased the phosphorylation of recombinant PHAS-I by mTOR in vitro. Wild-type PHAS-I, but none of the mutant proteins, was coimmunoprecipitated with hemagglutinin-tagged raptor, an mTOR-associated protein, after extracts of cells overexpressing raptor had been supplemented with recombinant PHAS-I proteins. Moreover, raptor overexpression enhanced the phosphorylation of wild-type PHAS-I by mTOR but not the phosphorylation of the mutant proteins. The results not only provide direct evidence that both the RAIP and tor signaling motifs are important for the phosphorylation by mTOR, possibly by allowing PHAS-I binding to raptor, but also support the view that mTOR phosphorylates PHAS-I in cells. | 10.1074/jbc.M301142200 |
others_18_9658 | 1. 1. Waste purines, proteins and carbohydrates were measured in the eggs of Heliothis virescens Fab. (a lepidopteran that lays cleidoic eggs) and Lygus hesperus Knight (a hemipteran that lays non-cleidoic eggs). 2. 2. As development progressed, total purines increased in both species with greater amounts present in the cleidoic eggs. 3. 3. Protein concentrations changed according to a "U" shaped pattern in L. hesperus but showed only a slight, but non-significant decrease in the cleidoic eggs of H. virescens. 4. 4. Glycogen decreased continuously throughout development of both species while free sugars increased in L. hesperus eggs and decreased in H. virescens eggs. 5. 5. A possible pattern of water uptake from surrounding plant tissues is suggested for the non-cleidoic eggs of L. hesperus. © 1986 | 10.1016/0305-0491(86)90075-1 |
pubmed_902_8860 | The factors which influence the formation of chelate, macrocycle or polymer in the reaction of silver(i) salts with bis(pyridine) ligands have been probed by studying structures in the solid state and cold spray ionization mass spectra in solution, with the ligands C(6)H(4)-1,3-[CONR(CH(2))(n)-3-C(5)H(4)N](2), 1 (R = Me, n = 0) or (R = H, n = 1) or 5-t-Bu-C(6)H(3)-1,3-[CONR(CH(2))(n)-4-C(5)H(4)N](2), 2 (R = Me, n = 0) or 4 (R = H, n = 1). In both the solid state and solution, the complex [Ag12)]BF(4) exists as a chelate complex 5. The ligands NN = 2-4 form complexes in the solid state with either macrocyclic structures [Ag(2)(mu-NN)(2)]X(2) [6, NN =2, X = BF(4); 9, NN = 3, X = NO(3)] or polymeric structures [7, NN = 2, X = NO(3); 8, NN = 3, X = CF(3)CO(2); 10, NN = 4, X = CF(3)CO(2)]. The ligands 2 and 3 gave both macrocyclic and polymeric complexes, depending on the anion. In solution, these complexes existed as mixtures of macrocycles and ring-opened oligomers. In the crystalline state, the complexes 6-10 underwent supramolecular association through combinations of hydrogen bonding, secondary bonding of the type Ag...X to anions, or argentophilic bonding of the type Ag...Ag. | 10.1039/b918615h |
others_342_10054 | : Lynch syndrome (LS), which is known as a hereditary cancer syndrome, is distinguished by microsatellite instability, represented by the altered number of repetitive sequences in the coding and/or non-coding region. Immunohistochemical staining (IHC) of DNA mismatch repair (MMR) proteins (e.g., MLH1, MSH2, MSH6, and PMS2) has been recognized as an useful technique for screening of LS. Previous study has shown that the assessment of IHC, however, requires specific caution due to variable staining patterns even without germline mutations in MMR genes. Case presentation: A 48-year-old man, who had been treated for anaplastic astrocytoma, was referred to our department for the precise examination of progressing anemia. Whole-body examination revealed two advanced carcinomas in descending colon and stomach. A hypo-vascular mass lesion was detected in liver as well. Pathological diagnosis (on surgical specimens) was poorly differentiated adenocarcinoma in descending colon, moderately differentiated tubular adenocarcinoma in stomach, and liver metastasis, which is possibly from colon. It was suspected that this case would be Turcot's syndrome-type-1 due to its specific family history having two cases of colon cancer within the second relatives. Pathogenic frameshift mutations in codon 618 of MLH1 gene was identified. Immunohistochemical analyses (IHC) demonstrated complete loss of MLH1 immuno-expression as well as of PMS2 except for those in brain tumor. Although frameshift mutation was not found in MSH6 gene, histological expression of MSH6 was patchy in primary colon carcinoma and was completely lost in the metastatic site in liver. MSH6 expression in gastric carcinoma, a coincidental cancer in this case, was intact. An abnormal (C)8 region was identified by the cloned PCR of colon and liver tumors but not from gastric cancer. Frameshift mutation in a (C)8 tract in exon 5 of the MSH6 gene was also detected in liver metastasis. Conclusion: This case supports a plausible mechanism, proposed by a previous literature, for the reduced expression of MSH6 in a somatic mutation manner, which might preferentially happen in colon cancer rather than in stomach carcinoma in MLH1/PMS2-deficient type of Turcot's syndrome type 1. © 2020 The Author(s) | 10.1186/s12881-020-01079-x |
pubmed_324_13164 | OBJECTIVE
Glucosamine is commonly used for the treatment of osteoarthritis. It is available as an over the counter preparation and also as a prescription pharmaceutical. There is concern from animal experiments that glucosamine may alter glucose metabolism through the hexosamine biosynthetic pathway. The objective of this systematic review is to determine if exogenous glucosamine adversely affects glucose metabolism in humans. This review does not separate out the effects on glucose metabolism of the various glucosamine preparations.
METHOD
An English-language literature search of MEDLINE, EMBASE and EBM Reviews (1950-February 2009) was conducted. The bibliographies of selected papers were manually searched for additional references. Two reviewers independently analyzed studies for quality and content using a standardized data extraction form.
RESULTS
Eleven studies were included. Six studies were randomized controlled trials and the remaining five were prospective studies with or without controls. Four of the studies found decreased insulin sensitivity or increased fasting glucose in subjects taking glucosamine. Three of these were clinical studies using oral glucosamine. Studies that included subjects with baseline impaired glucose tolerance or insulin resistance were more likely to detect an effect on glucose metabolism than studies without such subjects.
CONCLUSION
Clinical studies, including three using oral glucosamine, have provided mixed evidence about the effect of exogenous glucosamine on glucose metabolism in humans. Therefore, more studies are needed, particularly including subjects at high risk for impairments in glucose homeostasis, before a definite conclusion can be made. | 10.1016/j.joca.2011.01.007 |
pubmed_234_21168 | N-(2-hydroxyethyl)-piperazine-N'-2-ethanesulfonic acid, known as HEPES buffer, with pK in the physiological range was studied for use as an alternative to conventional phosphate buffer for the calibration of pH in modern clinical analyzers. In different series of aqueous equimolar HEPES buffer, pH was measured at 37 degrees C with a capillary glass electrode standardized previously using phosphate, and variations due to changes in total HEPES buffer concentration (0.025 to 0.320 mol/l), and NaCl (0 to 0.250 mol/l) were monitored. For 0.05 equimolar HEPES buffer without NaCl, the pH of 7.362+/-0.003 (n = 15) obtained coincided well with the reference pH (7.364) from the National Institute of Standards and Technology (NIST). In particular, in the preferred 0.05 equimolar HEPES buffer/0.110 mol/l NaCl, which is isotonic to human plasma (0.160 mol/l), and termed physiological HEPES buffer (PHB), the pH of 7.346+/-0.003 (n = 84) can be related to the calculated corresponding reference pH from NIST without liquid junction (7.374), and is also compatible with the pH measured in normal arterial blood, pH = 7.403+/-0.003 (n = 20). Hence, in the two-point calibration of clinical analyzers, PHB, which is defined operationally with respect to the glass electrode and to phosphate buffer, may be useful as a calibrator in the range of buffer adjustment control to meet the correct values for pH when measuring in blood. Whereas Na-HEPES salt is hygroscopic and does not meet the declared purity grade (> 99%), pure HEPES acid is non-hygroscopic and conforms to the manufacturer's purity grade (> or = 99%). Therefore, for easy preparation of PHB, HEPES acid is the preferred starting material. | 10.1515/CCLM.1999.090 |
pubmed_770_1352 | A total of 9440 Australian men and women of over 15 years of age was interviewed at home in 1986 to determine the prevalence and consumption levels of tobacco products. Current smokers were defined as those who smoked any combination of cigarettes, cigars or pipes regularly. The percentage of current smokers among men was 32.9% and among women was 28.5%, and the peak prevalence of smoking was in the age-group 20-24 years for both men (40.5%) and women (40.8%). Among men, 27.7% were past smokers, and among women, 16.5% were past smokers. The proportion of past smokers among those who had ever smoked was higher in men (0.46) than among women (0.37), but in the younger age groups there was no relative excess among men. Male smokers consumed more cigarettes per day than did female smokers and men were exposed to a higher daily average amount of cigarette tar. Sociodemographic variables that were associated with smoking in both men and women included age and educational and occupational level. Asian-born persons had a significantly lower prevalence of smoking than did persons who were born in Australia. | 10.5694/j.1326-5377.1988.tb120474.x |
pubmed_806_20695 | Primary immunodeficiencies (PIDs) include a heterogeneous group of mostly monogenic diseases characterized by functional/developmental alterations of the immune system. Skin and skin annexa abnormalities may be a warning sign of immunodeficiency, since both epidermal and thymic epithelium have ectodermal origin. In this review, we will focus on the most common immune disorders associated with ectodermal alterations. Elevated IgE levels represent the immunological hallmark of hyper-IgE syndrome, characterized by severe eczema and susceptibility to infections. Ectodermal dysplasia (ED) is a group of rare disorders that affect tissues of ectodermal origin. Hypoidrotic ED (HED), the most common form, is inherited as autosomal dominant, autosomal recessive or X-linked trait (XLHED). HED and XLHED are caused by mutations in NEMO and EDA-1 genes, respectively, and show similarities in the cutaneous involvement but differences in the susceptibility to infections and immunological phenotype. Alterations in the transcription factor FOXN1 gene, expressed in the mature thymic and skin epithelia, are responsible for human and murine athymia and prevent the development of the T-cell compartment associated to ectodermal abnormalities such as alopecia and nail dystrophy. The association between developmental abnormalities of the skin and immunodeficiencies suggest a role of the skin as a primary lymphoid organ. Recently, it has been demonstrated that a co-culture of human skin-derived keratinocytes and fibroblasts, in the absence of thymic components, can support the survival of human haematopoietic stem cells and their differentiation into T-lineage committed cells. | 10.3109/08830185.2015.1010724 |
pubmed_1108_15954 | For effective immunotherapy, maintaining the frequency and cytotoxic potential of effector cells is critical. In this context costimulation via the CD70/CD27 pathway has been proven essential. CD70 has been reported to be expressed to varying degrees on malignant B cells. However, in B cell precursor acute lymphoblastic leukemia, the most common childhood malignancy, the role of CD70 in stimulation of antileukemic T cell responses has so far not been delineated. Herein we demonstrate that in B cell precursor acute lymphoblastic leukemia expression of CD70 is low but can be induced upon blast activation via CD40. Both CD70 and CD80/CD86 up-regulated on CD40-stimulated blasts contribute to primary stimulation of T cell proliferation and cytokine production in an additive manner. These two signals also cooperate in the prevention of T cell anergy. In contrast to blockade of CD70 during the effector phase, inhibition of CD70-mediated costimulation during generation of antileukemic T cells prevents effector cell proliferation and reduces their cytotoxic capacity. Modulation of the CD70/CD27 pathway may thus represent a novel therapeutic approach for augmenting magnitude and quality of the antileukemic response in B cell precursor acute lymphoblastic leukemia. | 10.4049/jimmunol.182.1.718 |
pubmed_739_16886 | Interleukin-12 (IL-12) is a proinflammatory cytokine produced by antigen-presenting cells in response to many microbial infections. IL-12 plays an important role in the generation of T helper type-1 cells, which favor cell-mediated immune response. IL-12 is composed of two different subunits, p40 and p35, whose expression can be regulated concomitantly or differentially. Monocytic cells, the major producers of IL-12, can be primed by interferon-gamma (IFN-gamma) to produce optimal amounts of IL-12 in response to LPS stimulation as a consequence of bacterial infection. The priming effect is exerted primarily at the transcriptional level on the p40 promoter in conjunction with the effects of LPS, possibly by inducing specific transcription factors, which individually have no direct effect but which cooperatively can activate the promoter. We examined in detail one of these DNA-protein interactions observed around an Ets-2 element situated at -211/-207 of the p40 promoter, which is known to be a functionally critical site. This region interacts with a nuclear complex termed F1 that appears to be highly inducible by either IFN-gamma treatment for 16 h or lipopolysaccharide stimulation for 8 h. F1 binding to the Ets-2 site requires a considerable amount of spacing around the Ets-2 site, as revealed by gel mobility shift and in vitro methylation assays. Supershift experiments and DNA affinity purification indicated that both Ets-2 and a novel, antigenically related protein with an approximate molecular mass of 109 kDa are part of the F1 complex, together with additional components including IRF-1 and c-Rel. This novel protein is designated GLp109 for its inducibility by IFN-gamma or lipopolysaccharide. Its possible role in the activation of the IL-12 p40 promoter is discussed. | 10.1074/jbc.272.16.10389 |
pubmed_24_13655 | Autopsy results: Hemorrhagic infarction of jejunum due to essential eosinophilia, infarction of portal vein, and disseminated intra-vascular coagulation. | pubmed_24_13655 |
pubmed_377_23251 | A green analytical method was developed for the analysis of sugar-based depilatories. Three independent partial least squares (PLS) regression models were built for the direct determination of glucose, fructose and maltose without any sample pretreatment based on their attenuated total reflectance - Fourier transform infrared (ATR-FTIR) spectra. The models showed adequate prediction capabilities with root-mean-square-errors of prediction ranging from 7.04 to 12.55 mg sugar g(-1) sample. As a reference procedure, gradient liquid chromatography with on-line infrared detection, employing background correction based on cubic smoothing splines, was used. The analysis revealed changes in the sugar concentration due to the formulation process as compared to information on the ingredients provided by the manufacturers. Although fructose, glucose and sucrose were declared to be used for the production of depilatories, in the final products only fructose, glucose and maltose were determined. This fact was attributed to pH and temperature conditions employed during the production process as well as to the use of glucose syrup instead of crystalline glucose. The present ATR-FTIR-PLS method enables an accurate, cheap and fast determination without solvent consumption or toxic waste generation and offers therefore a green screening alternative to methods employing chromatographic techniques. | 10.1016/j.talanta.2011.06.040 |
pubmed_902_5461 | PURPOSE
To estimate the prevalence of and risk factors for cataracts in the Kandy District of central Sri Lanka.
METHODS
A population-based, cross-sectional ophthalmic survey of the inhabitants of rural villages in central Sri Lanka was conducted; 1375 individuals participated (79.9%; age > or = 40 years, average age 57) and 1318 (95.9%) had an examinable lens in at least one eye. Data collection included district, age, occupation, education level, smoking history, height, weight and dilated lens assessment using Lens Opacities Classification System III grading: nuclear (> or =4), cortical (> or =2) and posterior subcapsular (> or =2) cataracts. Aphakic and pseudophakic eyes were included as operated cataracts for statistical analysis.
RESULTS
The prevalence of any cataract including operated eyes was 33.1% (95% Confidence Interval (CI), 22.4-43.7%): 26.0% cortical; 7.9% posterior sub-capsular and 4.5% nuclear cataracts. No significant association was found between cataract and gender, smoking or outdoor occupation. Low level of education (secondary or higher vs no education: Odds Ratio (OR) 0.6, CI 0.4-0.9, P = 0.04) and shorter stature were associated with a higher likelihood of any cataract (OR 1.7, CI 1.1-2.7, P = 0.02).
CONCLUSIONS
The overall prevalence of cataract in central Sri Lanka is similar to that in other developing Asian regions except for the unusually low prevalence of nuclear cataract. Illiteracy and height appear to be significant predictors for cataract in this population and further investigation is required to explore their influence. | 10.3109/09286580903324900 |
pubmed_1057_22054 | Additives are added to polymers in small concentration to achieve desired application properties widely used to tailor the properties. The rapid diversification of their molecular structures, with often only minute differences, necessitates the development of adequate chromatographic techniques. While modified silica so far is the workhorse as stationary phase we have probed the potential of porous graphitic carbon (HypercarbTM) for this purpose. The results show that the multitude of physicochemical interactions between analyte molecules and the graphitic surface enables separations of polyolefin stabilizers with unprecedented selectivity. To support the chromatographic results the adsorption capability of HypercarbTM for selected antioxidants and UV absorbers has been determined by Raman spectroscopy and argon physisorption measurements. The shift of the Graphite-band in the Raman spectra of HypercarbTM upon infusion with additives correlates with the changes in the Adsorption Potential Distributions. The results of argon physisorption measurements go hand in hand with the chronology of desorption of the additives in liquid chromatography experiments. The elution sequence can be explained by van der Waals or London forces, π-π-interactions and electron lone pair donor-acceptor interactions between the graphite surface and analyte functional groups. | 10.1016/j.chroma.2020.461302 |
pubmed_120_8571 | PURPOSE
The purpose of this research was to determine if differences in service use exist between dementia patients with and without psychiatric comorbidity.
DESIGN AND METHODS
A retrospective cohort study was conducted on all Veterans Affairs (VA) beneficiaries seen at the Houston Veterans Affairs Medical Center with a VA Outpatient Clinic File diagnosis of dementia in 1997. The primary dependent measure was amount of Houston VA health service use from study entry until the end of fiscal year 1999 or until death.
RESULTS
Of the 864 dementia patients in the identified cohort, two thirds had a comorbid psychiatric diagnosis. Examination of 2-year health service use revealed that, after adjusting for demographic and medical comorbidity differences, dementia patients with psychiatric comorbidity had increased medical and psychiatric inpatient days of care and more psychiatric outpatient visits compared with patients without psychiatric comorbidity.
IMPLICATIONS
Further understanding of the current health service use of dementia patients with psychiatric comorbidity may help to establish a framework for considering change in the current system of care. A coordinated system of care with interdisciplinary teamwork may provide both cost-effective and optimal treatment for dementia patients. | 10.1093/geront/43.1.86 |
pubmed_721_15944 | Scintigraphy with 123I-radiolabeled metaiodobenzylguanidine (MIBG) was performed successfully in two patients with metastatic carcinoid tumor. The scintigraphic findings show diversity of the tumor deposits in the uptake of [123I]MIBG in the same patient and between patients. | pubmed_721_15944 |
pubmed_162_10951 | BACKGROUND
Stroke is the number one cause of adulthood disability in Korea. Rehabilitation after stroke can minimize functional disability, enhance recovery toward independence, and optimize community reintegration. The inter-departmental stroke meeting (IDSM) is a potential method to improve rehabilitation outcomes in patients with stroke. We aimed to analyze the effect of IDSM on rehabilitation after acute ischemic stroke management.
METHODS
Medical records of 753 patients with acute ischemic stroke admitted to the neurology department of our medical center between January and December 2014 were reviewed retrospectively. In May 2014, weekly IDSMs were initiated. All physicians responsible for the patient's care reviewed patient treatment, methods of secondary prevention, and future rehabilitation plans.
RESULTS
The transfer rate significantly increased after initiation of IDSM (phase 2, 3) and the length of stay (LOS) before transfer to the rehabilitation department decreased significantly from 9.68 ± 8.50 days to 5.75 ± 2.12 days. There was a reduction in the total LOS from 52 ± 28.57 days to 35 ± 27.21 days after IDSMs were introduced. In non-transferred patients also, the total LOS reduced significantly. The transfer rate increased significantly and the LOS before transfer to the rehabilitation department decreased significantly after implementation of IDSM in a subgroup of patients with moderate to severe stroke.
CONCLUSION
The introduction of IDSM was significantly correlated with improvements in transfer rates and reduction of LOS in hospital. This finding shows that IDSMs are an important intervention to improve therapeutic progress and outcomes for patients with stroke. | 10.3346/jkms.2018.33.e85 |
pubmed_846_3237 | Catheter-tipped micromanometers were used to simultaneously record left ventricular and aortic pressures, and left ventricular and aortic internal phonocardiograms in order to determine if they had a common mode of origin and propagation. Spectrographic analysis showed that even with high-pass filtration the phonocardiogram obtained with a commonly used system (Millar) contained large amounts of energy in the subaudible frequency range (below 40 Hz). It was possible to derive close facsimiles of the phonocardiograms by double differentiation of the corresponding pressure pulse and conversely to derive the pressure pulse by double integration of the phonocardiograms. The propagation velocities of the first heart sound, second heart sound, and the foot of the aortic pressure pulse were found to be similar and were respectively, 4.3 +/- 0.2, 4.6 +/- 0.3, and 4.2 +/- 0.2 m/sec (+/- SE). These data support the concept that the low frequency pressure variations produced by the heart, which predominate in the left ventricular and aortic pressure pulse waveforms, are generated and propagated in the same manner as the high frequency pressure variations, which are the first and second heart sounds. | 10.1016/0002-8703(82)90161-2 |
pubmed_414_6474 | OBJECTIVE
To evaluate the quality of care for mastitis managed by telephone without an office or emergency room visit.
STUDY DESIGN
A word search of electronic medical records allowed for identification of patients managed with a mastitis clinical practice guideline. Comparisons of outcomes were made to a group of patients who received care in the clinic, urgent care or emergency room.
RESULTS
Rates of successful resolution with 1 encounter were 86% for telephone-based care and 82% for visit-based care (p = 0.550). Antibiotic selection was enhanced by use of the standing order.
CONCLUSION
Telephone-based management of mastitis may be safe, effective, and efficient. | pubmed_414_6474 |
pubmed_708_15720 | Lung carcinomas are characterised by considerable histological variation within the tumour. The possible effects of this morphological heterogeneity on the estimation of tumour ploidy were investigated. Multiple tissue blocks were systematically taken from 20 lung tumours and analysed by flow cytometry. The routine, archival paraffin wax embedded diagnostic blocks from these cases were also analysed. Nineteen (95%) of the tumours were shown to contain aneuploid stemlines by systematic sampling, but if only one of these systematic tissue blocks had been taken from each case the incidence of DNA aneuploidy could have been as low as 45%. Only 15 (75%) tumours were aneuploid when all the routine archival blocks were analysed, but by specifically selecting tumour areas from the archival material the accuracy of this method was increased to 90%. It is concluded that tumour sampling methods are of primary importance in assessing the DNA content of lung tumours. Routine paraffin wax embedded archival tissue provides a suitable source of material for this purpose, provided that "turnover" selection is carried out. | 10.1136/jcp.43.10.820 |
pubmed_48_2135 | BACKGROUND
The clinicopathological features of mixed-type (MT) early gastric cancer (EGC) according to Lauren's classification remain uninvestigated. This study aimed to clarify the clinicopathological features of MT EGC, particularly in relation to lymph node metastasis (LNM) and long-term survival.
METHODS
This study included 5309 patients who underwent gastrectomy for EGC. The clinicopathological features, LNM, and long-term outcomes of patients with MT carcinomas were compared with those of patients with intestinal-type (IT) and diffuse-type (DT) cancers. Furthermore, we evaluated the predictors of LNM in each Lauren classification subgroup.
RESULTS
Patients with MT carcinomas were likelier to have larger tumors, submucosal invasion, lymphovascular invasion, and LNM than those with IT or DT carcinomas. Multivariate logistic regression analysis revealed that the Lauren classification was a significant predictor of LNM (P < 0.001). The significant predictors of LNM in MT carcinomas were female sex, greater tumor size, presence of submucosal invasion, and lymphovascular invasion. However, the overall survival of patients with MT carcinoma was not significantly different from that of patients with IT or DT carcinomas (P = 0.104).
CONCLUSIONS
The presence of MT EGC carries a higher risk of LNM compared with the presence of IT or DT carcinomas. Therefore, MT carcinomas should be managed with gastrectomy that includes lymph node dissection instead of endoscopic resection. | 10.1007/s00535-016-1254-5 |
pubmed_470_21350 | The transmission of scientific seminars into the Internet represents a new application of modern technologies for teleteaching. We digitally recorded 74 seminars and discussions during the 8th annual meeting of the German Society of Skull Base Surgery with five cameras and eight microphones, and transformed the data live with the real-Producer using a video card.This transferred data stream was sent via ISDN (128 kbit/s) to a real-server at the university, which was used for distribution in the net. The seminars could be called up in the display format of 320x240 pixels with a delay of 3 min (minimum: 30 s, as a function of the connection of the user) at each computer with Internet entrance. Altogether,we registered 3,284 accesses to the presentations following the congress until June 2002. The quality of picture transmission (24-36 kbit/s) and the quality of tone (audio stream: 5 kbit/s) were sufficient to understand the contents of the slide, video or computer presentation. The transmission of scientific meetings into the Internet can increase, with a justifiable technical expenditure, their efficiency by the ubiquitous availability of the information and the extension of the audience. | 10.1007/s00106-002-0752-3 |
pubmed_625_3798 | Transforming growth factor (TGF)-β is a multifunctional peptide growth factor that has a vital role in the regulation of cell growth, differentiation, inflammation, and repair in a variety of tissues, and its dysregulation mediates a number of pathological conditions including fibrotic disorders, chronic inflammation, cardiovascular diseases, and cancer progression. Regulation of TGF-β signaling is multifold, but one critical site of regulation is via interaction with certain extracellular matrix (ECM) microenvironments, as TGF-β is primarily secreted as a biologically inactive form sequestrated into ECM. Several ECM proteins are known to modulate TGF-β signaling via cell⁻matrix interactions, including thrombospondins, SPARC (Secreted Protein Acidic and Rich in Cystein), tenascins, osteopontin, periostin, and fibulins. Fibulin family members consist of eight ECM glycoproteins characterized by a tandem array of calcium-binding epidermal growth factor-like modules and a common C-terminal domain. Fibulins not only participate in structural integrity of basement membrane and elastic fibers, but also serve as mediators for cellular processes and tissue remodeling as they are highly upregulated during embryonic development and certain disease processes, especially at the sites of epithelial⁻mesenchymal transition (EMT). Emerging studies have indicated a close relationship between fibulins and TGF-β signaling, but each fibulin plays a different role in a context-dependent manner. In this review, regulatory interactions between fibulins and TGF-β signaling are discussed. Understanding biological roles of fibulins in TGF-β regulation may introduce new insights into the pathogenesis of some human diseases. | 10.3390/ijms19092787 |
pubmed_431_22076 | Chronic wounds, defined as those wounds which fail to proceed through an orderly process to produce anatomic and functional integrity, are a significant socioeconomic problem. A wound may fail to heal for a variety of reasons including the use of corticosteroids, formation of squamous cell carcinoma, persistent infection, unrelieved pressure, and underlying hypoxia within the wound bed. Hypoxia appears to inhibit the wound healing process by blocking fibroblast proliferation, collagen production, and capillary angiogenesis and to increase the risk of infection. Hyperbaric oxygen therapy (HBOT) has been shown to aid the healing of ulcerated wounds and demonstrated to reduce the risk of amputation in diabetic patients. However, the causal reasons for the response of the underlying biological processes of wound repair to HBOT, such as the up-regulation of angiogenesis and collagen synthesis are unclear and, consequently, current protocols remain empirical. Here we review chronic wound healing and the use of hyperbaric oxygen as an adjunctive treatment for nonhealing wounds. Databases including PubMed, ScienceDirect, Blackwell Synergy, and The Cochrane Library were searched for relevant phrases including HBOT, HBO/HBOT, wound healing, and chronic/nonhealing wounds/ulcers. | 10.1111/j.1524-475X.2008.00372.x |
pubmed_969_18199 | The effect of bleomycin (BLM) on the growth of the tumor, murine B16 melanoma, implanted onto the chorioallantoic membrane of chick embryo was examined. The inhibition ratio of BLM was about 30% at 3 micrograms/egg. This inhibitory effect of BLM on the growth of the tumor was enhanced by an appropriate dose of ultraviolet (UV) irradiation. The inhibition ratios of BLM irradiated for 10, 30 and 60 min were in order of about 50, 30 and 30% at 3 micrograms/egg. However, when these BLMs pretreated with 1 mM 1,2-benzenediol (catechol) were administrated, the inhibition ratios of BLM irradiated for 0, 10, 30 and 60 min were about 30, 20, 10 and 10%, respectively. On the other hand, the direct cytotoxicity of BLM to cultured murine B16 melanoma cells was depressed with UV irradiation and its toxic activity was further decreased by treatment with catechol after irradiation. These findings show that, although the antitumor activity of BLM is enhanced by UV irradiation, the activity of UV-irradiated BLM is inhibited by catechol. Moreover, it seems to show that the present results may provide a useful manner for the in vivo activation of BLM. | 10.1248/cpb.38.1400 |
pubmed_687_25201 | CDATA[Osteoporosis is a pathological loss of bone mass due to an imbalance in bone remodeling where osteoclast-mediated bone resorption exceeds osteoblast-mediated bone formation resulting in skeletal fragility and fractures. Anti-resorptive agents, such as bisphosphonates and SERMs, and anabolic drugs that stimulate bone formation, including PTH analogues and sclerostin inhibitors, are current treatments for osteoporosis. Despite their efficacy, severe side effects and loss of potency may limit the long term usage of a single drug. Sequential and combinational use of current drugs, such as switching from an anabolic to an anti-resorptive agent, may provide an alternative approach. Moreover, there are novel drugs being developed against emerging new targets such as Cathepsin K and 17β-HSD2 that may have less side effects. This review will summarize the molecular mechanisms of osteoporosis, current drugs for osteoporosis treatment, and new drug development strategies. | 10.2174/0929867327666200330142432 |
pubmed_263_11385 | The assembly of the ribosome on majority of eukaryotic mRNAs is initiated by the recruitment of eIF4E protein to the mRNA 5' end cap structure. Flowering plants use two eIF4E isoforms, named eIF4E and eIF(iso)4E, as canonical translation initiation factors and possess a homolog of mammalian 4EHP (or eIF4E-2) termed nCBP. Plants from Brassicaceae family additionally conserve a close paralog of eIF4E which in Arabidopsis thaliana has two copies named eIF4E1b and eIF4E1c. In order to assess the efficiency of plant non-canonical (eIF4E1b/1c and nCBP) and canonical (eIF4E and eIF(iso)4E) eIF4E proteins to bind mRNAs we utilized fluorescence titrations to determine accurate binding affinities of five A.thaliana eIF4E isoforms for a series of cap analogs. We found that eIF4E binds cap analogs from 4-fold to 10-fold stronger than eIF(iso)4E, while binding affinities of nCBP and eIF(iso)4E are comparable. Furthermore, eIF4E1c interacts similarly strongly with the cap as eIF4E, but eIF4E1b binds cap analogs ca. 2-fold weaker than eIF4E1c, regardless of the 95% sequence identity between these two proteins. The use of differentially chemically modified cap analogs in binding studies and a detailed analysis of the obtained homology models gave us insight into the molecular characteristic of varying cap-binding abilities of Arabidopsis eIF4E isoforms. | pubmed_263_11385 |
pubmed_1025_10369 | The adult mammalian central nervous system has a limited ability to establish new connections and to recover from traumatic or degenerative events. The olivo-cerebellar network represents an excellent model to investigate neuroprotection and repair in the brain during adulthood, due to its high plasticity and ordered synaptic organization. To shed light on the molecular mechanisms involved in these events, we focused on the growth-associated protein GAP-43 (also known as B-50 or neuromodulin). During development, this protein plays a crucial role in growth and in branch formation of neurites, while in the adult it is only expressed in a few brain regions, including the inferior olive (IO) where climbing fibres (CFs) originate. Following axotomy GAP-43 is usually up-regulated in association with regeneration. Here we describe an in vivo lentiviral-mediated gene silencing approach, used for the first time in the olivo-cerebellar system, to efficiently and specifically downregulate GAP-43 in rodents CFs. We show that lack of GAP-43 causes an atrophy of the CF in non-traumatic conditions, consisting in a decrease of its length, branching and number of synaptic boutons. We also investigated CF regenerative ability by inducing a subtotal lesion of the IO. Noteworthy, surviving CFs lacking GAP-43 were largely unable to sprout on surrounding Purkinje cells. Collectively, our results demonstrate that GAP-43 is essential both to maintain CFs structure in non-traumatic condition and to promote sprouting after partial lesion of the IO. | 10.1371/journal.pone.0020791 |
pubmed_70_9602 | Hemispheric involvement in reasoning abilities has been debated for some time, and it remains unclear whether the right hemisphere's involvement in problem solving is modality specific or dependent on the type of spatial reasoning required. In the current study, 2 types of nonverbal reasoning abilities were examined, spatial reasoning and proportional reasoning, in 109 patients with cerebrovascular disease that was confined to either the right or the left hemisphere or was diffuse in nature. Results indicated that no lateralizing effects were present based on type of spatial reasoning. Findings are consistent with the suggestion that higher order cognitive processes involved in nonverbal abstraction and problem solving are not strongly lateralized to the right hemisphere but rather are more generally distributed throughout the cortex. | 10.1037/0894-4105.21.6.713 |
pubmed_137_20923 | The growth of a cell population from a large inoculum appears deterministic, although the division process is stochastic at the single-cell level. Microfluidic observations, however, display wide variations in the growth of small populations. Here we combine theory, simulations and experiments to explore the link between single-cell stochasticity and the growth of a population starting from a small number of individuals. The study yields descriptors of the probability distribution function (PDF) of the population size under three sources of stochasticity: cell-to-cell variability, uncertainty in the number of initial cells and generation-dependent division times. The PDF, rescaled to account for the exponential growth of the population, is found to converge to a stationary distribution. All moments of the PDF grow exponentially with the same growth rate, which depends solely on cell-to-cell variability. The shape of the PDF, however, contains the signature of all sources of stochasticity, and is dominated by the early stages of growth, and not by the cell-to-cell variability. Thus, probabilistic predictions of the growth of bacterial populations can be obtained with implications for both naturally occurring conditions and technological applications of single-cell microfluidics. | 10.1098/rsif.2018.0935 |
pubmed_445_13594 | Three strains of Epstein-Barr virus (EBV), two from Burkitt lymphoma (BL) and one from infectious mononucleosis (IM) were used to transform separate cultures of the same batch of primary marmoset leukocytes, and the viruses released from the transformants were compared. The three viruses shared properties of the transforming biotype of EBV, namely, stimulation of DNA synthesis and immortalization of cord blood leukocytes, and failure to induce "early antigen" in lymphoblast lines. All viruses produced more virus in transformed marmoset cells than in transformed human cells, as measured by the number of EBV genomes detected by complementary RNA/DNA hybridization, by virus capsid antigen expression, or by released virions and biologically active virus. Reference human sera and sera from primary EBV infections were used to compare the three virus strains in a virus neutralization test based on inhibition of stimulation of DNA synthesis. Specimens taken late in convalescence from patients with mononucleosis and sera from marmosets experimentally infected with virus from a patient with mononucleosis neutralized the homologous virus, as well as the two virus strains isolated from patients with BL. This finding indicates that viral antigens that elicit neutralizing antibodies are shared among the strains. However, in certain sera the neutralizing-antibody titer against one strain was consistently higher than against another strain. Furthermore, sera taken early after onset of IM contained low levels of neutralizing antibody against IM-derived virus, but failed to neutralize BL-derived virus. These latter findings suggest the existence of heterogeneity among surface antigens of EBVs. The results emphasize the biological and antigenic similarity of EBV isolates from BL and IM and do not suggest major subtype variations. It remains to be determined whether antigenic diversity such as described or virus genome variation detectable by other means is epidemiologically significant. | 10.1128/JVI.18.3.1071-1080.1976 |
pubmed_339_18289 | Patients with unstable angina or non-ST segment elevation (non-Q-wave) myocardial infarction are a heterogeneous group with respect to their risk of developing clinically significant adverse events such as subsequent myocardial infarction and death. Recent guidelines promote risk stratification of these patients, targeting high-risk patients for maximal antithrombotic and antiischemic therapy and low-risk patients for early discharge. We reviewed current and future modalities for risk stratification of patients and the predictive value of these methods in context with available pharmacologic agents. Unfortunately, most of the data identifying a particular pharmacologic regimen as beneficial in high-risk patients are retrospectively derived from large trials. Until prospective studies that use markers to guide therapy are available, clinicians should be familiar with the use of these risk markers and their application to the role of a given management strategy, including pharmacologic therapy. | 10.1592/phco.21.11.954.34527 |
pubmed_617_3108 | Moniliophthora perniciosa and Moniliophthora roreri are phytopathogenic basidiomycete species that infect cacao causing two important diseases in this crop: "Witches' Broom" and "Frosty Pod Rot", respectively. The ability of species from this genus (Moniliophthora) to cause disease is exceptional in the family Marasmiaceae. Species in closely related genera including, Marasmius, Crinipellis, and Chaetocalathus, are mainly saprotrophs and are not known to cause disease. In this study, the possibility that this phytopathogenic lifestyle has been acquired by horizontal gene transfer (HGT) was investigated. A stringent genome comparison pipeline was used to identify potential genes that have been obtained by Moniliophthora through HGT. This search led to the identification of three genes: a metallo-dependent hydrolase (MDH), a mannitol phosphate dehydrogenase (MPDH), and a family of necrosis-inducing proteins (NEPs). Phylogenetic analysis of these genes suggests that Moniliophthora acquired NEPs from oomycetes, MDH from actinobacteria and MPDH from firmicutes. Based on the known gene functions and on previous studies of M. perniciosa infection and development, a correlation between gene acquisition and the evolution of the phytopathogenic genus Moniliophthora can be postulated. | 10.1007/s00239-009-9311-9 |
pubmed_118_12619 | Safe management of nuclear legacies arising from past activities is a critical issue in maintaining confidence for the continuing and future use of radioactive materials. Effective and efficient regulatory supervision of nuclear legacy management is a critical part of that process. The Norwegian Radiation Protection Authority plays an active role in bilateral regulatory cooperation projects with sister authorities in the Russian Federation, as part of Norway's Plan of Action to improve radiation and nuclear safety. Based on this experience and by reference to specific legacy sites and facilities, this study provides an overview of the substantial progress made in remediation at the Site of Temporary Storage for spent fuel and radioactive waste at Andreeva Bay and presents radiation protection issues arising from the experience and lessons learned in this work. It is suggested that this experience can be useful in the further development of international recommendations, standards and guidance on remediation of nuclear legacies. | 10.1093/rpd/ncw340 |
pubmed_699_25967 | PURPOSE
Following shifts that broadened the medical profession's conceptualization of the underlying drivers of health, medical schools are required to integrate curricula on health disparities and the social context of medicine into undergraduate medical education. Although previous research has focused on student experiences and outcomes in these curricula, less attention has been paid to the experiences of the physician-faculty involved. This study aimed to capture faculty insights to improve understanding of the challenges and opportunities of implementing this curricular reform.
METHOD
In-depth, semistructured interviews were conducted with 10 faculty members at one U.S. medical school in spring 2019 to capture their experiences designing and teaching a new curriculum related to the social determinants of health and health disparities. Study design, including interview guide development, was informed by the critical pedagogy perspective and social constructionist approaches to curriculum implementation. With the use of a constructivist grounded theory approach, interview transcripts were analyzed using open, thematic, and axial coding techniques. Primary themes were categorized as professional, organizational, interactional, or intrapersonal and organized into the final model.
RESULTS
Participants processed their experiences at 4 concentric levels: professional, organizational, interactional, and intrapersonal. Faculty generally embraced the movement to incorporate more discussion of social context as a driver of health outcomes. However, they struggled with the shortcomings of their training and navigating structural constraints within their school when developing and delivering content. When confronted with these limitations, faculty experienced unexpected tension in the classroom setting that catalyzed self-reflection and reconstruction of their teaching approach.
CONCLUSIONS
Findings highlight the challenges that faculty encounter when integrating social determinants of health and related curricula into undergraduate medical education. They also speak to the need for a broader conceptualization of relevant expertise and have implications for how medical schools select, train, and support medical educators in this work. | 10.1097/ACM.0000000000004804 |
pubmed_518_1423 | The authors present a case of a papillary type renal cell carcinoma. The tumor is mostly discovered accidentally; a histopathological evaluation is indispensable for an exact diagnosis. Because of a better prognosis, differentiation of this tumor type from the classic variant of renal cell carcinoma is necessary, however, the contralateral appearance of a second tumor is not to be excluded, which necessitates a strict patient follow-up. Prevalence of this tumor is higher in patients with chronic dialysis. | pubmed_518_1423 |
pubmed_552_20303 | An improved characterization of cattle chromosomes was obtained by means of high-resolution G- and R-band comparison. Models of G- and R-banded karyotypes that were arranged according to the Reading system and the previous RBA-banded karyotype were obtained at the 475 band level by using early- and late-BrdU incorporation in synchronized cell cultures. As in human chromosomes, only one common G- and R-banding nomenclature is proposed. | 10.1093/oxfordjournals.jhered.a110933 |
pubmed_1107_20504 | Near-infrared spectroscopy, a new non-invasive technique, measures changes in the hemoglobin oxygenation state, blood volume, and redox state of cytochrome oxidase (cyt. ox.) in tissues. This technique now finds wide clinical applications, while the specificity and accuracy of the measurement of the redox state of cyt. ox. is still controversial. Recently, we have developed a new approach to measure the redox state of cyt. ox. This method has overcome several technological problems such as difficulty in determination of the in vivo absorption coefficient for cyt. ox. We describe here this new method briefly and the significance of the measurement of the redox state of cyt. ox. in the clinical medicine. | pubmed_1107_20504 |
pubmed_787_5231 | We explored the potential of the cox1 gene in the species resolution of soil fungi and compared it with the nuclear internal transcribed spacer (ITS) and small subunit (SSU)-rDNA. Conserved primers allowing the amplification of the fungal cox1 gene were designed, and a total of 47 isolates of Zygomycota and Ascomycota were investigated. The analysis revealed a lack of introns in >90% of the isolates. Comparison of the species of each of the six studied genera showed high interspecific sequence polymorphisms. Indeed, the average of nucleotide variations (4.2-11%) according to the genus, due mainly to the nucleotide substitutions, led to the taxonomic resolution of all the species studied regarding both ITS and SSU-rDNA, in which <88% were discriminated. The phylogenetic analysis performed after alignment of the cox1 gene across distant fungal species was in accordance with the well-known taxonomic position of the species studied and no overlap was observed between intra- and interspecific variations. These results clearly demonstrated that the cox1 sequences could provide good molecular markers for the determination of the species composition of environmental samples and constitute an important advance to study soil fungal biodiversity. | 10.1111/j.1574-6968.2009.01839.x |
pubmed_156_7834 | The aim of these studies was to investigate the effect of hyperglycemia with or without hyperinsulinemia on hepatic gluconeogenic flux, with the hypothesis that inhibition would be greatest with combined hyperglycemia/hyperinsulinemia. A glycogen phosphorylase inhibitor (BAY R3401) was used to inhibit glycogen breakdown in the conscious overnight-fasted dog, and the effects of a twofold rise in plasma glucose level (HI group) accompanied by 1) euinsulinemia (HG group) or 2) a fourfold rise in plasma insulin were assessed over a 5-h experimental period. Hormone levels were controlled using somatostatin with portal insulin and glucagon infusion. In the HG group, net hepatic glucose uptake and net hepatic lactate output substantially increased. There was little or no effect on the net hepatic uptake of gluconeogenic precursors other than lactate (amino acids and glycerol) or on the net hepatic uptake of free fatty acids compared with the control group. Consequently, whereas hyperglycemia had little effect on gluconeogenic flux to glucose 6-phosphate (G-6-P), net hepatic gluconeogenic flux was reduced because of increased hepatic glycolytic flux during hyperglycemia. Net hepatic glycogen synthesis was increased by hyperglycemia. The effect of hyperglycemia on gluconeogenic flux to G-6-P and net hepatic gluconeogenic flux was similar. We conclude that, in the absence of appreciable glycogen breakdown, the increase in glycolytic flux that accompanies hyperglycemia results in decreased net carbon flux to G-6-P but no effect on gluconeogenic flux to G-6-P. | 10.1152/ajpendo.00211.2003 |
pubmed_189_13125 | Background
People with mental health problems are at particular risk both for infection with COVID-19 and for more severe course of illness. Understanding COVID-19 vaccine hesitancy is crucial in promoting vaccine acceptance among people with mental health diagnoses. This review aims to identify the prevalence and discuss factors associated with COVID-19 vaccine hesitancy among the mentally ill population.
Main body
We conducted a detailed literature search and included 15 articles for discussion in this review. Several studies showed varying trends of vaccine hesitancy rates among different countries. Major factors involved in vaccine hesitancy in general include mistrust, misinformation, believing in conspiracy theories, and negative attitudes towards vaccines. It was surprising that none of the studies were focused on vaccine acceptance rates and factors associated with vaccine hesitancy among the mentally ill population. However, studies do show that COVID-19 is associated with worse healthcare outcomes for psychiatric patients, and vaccine hesitancy correlated with a lower likelihood of receiving mental health treatment and vaccinations. Psychiatrists need to address issues among patients who are particularly vulnerable to the fear of vaccines which include anxiety, panic attacks, certain phobias including trypanophobia and agoraphobia, obsessive-compulsive disorder, and certain types of traumas. Psychiatrists need to communicate effectively, show respect, empathy, and deliver accurate and honest information about the vaccines. Motivational interviewing, getting people with mental health illness to organize vaccine campaigns, and involving families with mental health problems may promote vaccine acceptance among this group.
Conclusion
Existing literature on the rates of vaccine hesitancy among people with mental health illness is limited. The mental health illness may increase the risk of hesitancy especially in patients having certain emotional disorders such as anxiety and phobia. More studies addressing vaccine hesitancy rates and factors associated with the mentally ill population need to be done in the future. | 10.1186/s42506-022-00102-8 |
pubmed_348_9604 | We describe the case of a 24-year old male who had been a heavy smoker since the age of 9 and who presented with an 8-year history of respiratory symptoms. He was having treatment for asthma. Spirometric studies and high-resolution computed tomography (HRCT) scans confirmed COPD with centrilobular emphysema. His blood level of alpha-1-antitrypsin was within the normal range. Early onset emphysema in smokers with a normal alpha-1-antitrypsin has been previously described. However, this case is, as far as we know, one of the youngest cases ever reported. | 10.3132/pcrj.2007.00082 |
pubmed_1121_22190 | The increasing number of cesarean sections worldwide has encouraged research on the long-term effects of this birth type on the offspring's mental health. The objective of this study was to investigate whether there is an association between birth by cesarean section and the development of mood disorders (depression and bipolar disorders) in adolescents. A cohort study was carried out with 1603 adolescents from 18 to 19 years old who participated in the third phase of a birth cohort study in São Luís, MA, in 2016. Information on birth type and weight, prematurity, mother's age and schooling, parity, marital status, and smoking behavior during pregnancy, were collected at birth. The study outcomes were depression, bipolar disorder, and "mood disorder" construct. A Directed Acyclic Graph (DAG) was developed to select the variables for minimal adjustment for confounding and collision bias. Associations were estimated through propensity score weighting using a two-step estimation model, and confounders for cesarean birth were used in the predictive model. There was no significant association in the relationship between birth type and depression (95%CI: -0.037 to 0.017; P=0.47), bipolar disorder (95%CI: -0.019 to 0.045; P=0.43), and mood disorder (95%CI: -0.033 to 0.042; P=0.80) in adolescents of both sexes. Birth by cesarean section was not associated with the development of mood disorders in adolescents. | 10.1590/1414-431X202010285 |
pubmed_636_1933 | A novel isolate, designated 6408J-67(T), was isolated from an air sample collected from Jeju Island, Republic of Korea. Its phenotypic, genotypic, and chemotaxonomic properties were compared with those of members of the family Microbacteriaceae. The Gram-positive, aerobic, motile rod formed light yellow, smooth, circular and convex colonies. Optimal growth occurred at 30°C and pH 7.0. 16S rRNA gene sequence data showed that the isolate was a novel member of the family Microbacteriaceae, with the highest sequence similarity (97.4%) to Labedella gwakjiensis KSW2-17(T) and less (<97%) sequence similarity with other taxa. The major cellular fatty acids (>10% of the total) were anteiso-C(15:0), iso-C(14:0), and iso-C(16:0). The strain also contained MK-13, MK-12, and MK-14 as the major menaquinones, as well as diphosphatidylglycerol, phosphatidylglycerol, and two unknown glycolipids. Its peptidoglycan structure was B1β with 2,4-diaminobutyric acid as a diamino acid. Mycolic acids were absent. The DNA G+C content was 68.3 mol%. Based on these phenotypic and genotypic findings, strain 6408J-67(T) represents a novel species of a new genus within the family Microbacteriaceae, for which the name Diaminobutyricimonas aerilata gen. nov., sp. nov. is proposed. The type strain is 6408J-67(T) (=KACC 15518(T) =NBRC 108726(T)). | 10.1007/s12275-012-2118-1 |
pubmed_180_10022 | The lateral orbital wall is the strongest among other orbital walls. However, it is commonly fractured in the setting of severe facial trauma. The fracture usually occurs at the sphenozygomatic suture line. In general, patients with lateral wall fractures are commonly young male who may present with mid facial swelling and some degree of deformity. In some cases, lateral orbital wall fracture may be associated with visual loss or change in mental status due to associated intracranial injury. Imaging studies with computed tomography is important in the proper diagnosis and planning of the surgical intervention. Management of intracranial or eye injuries should be undertaken on emergent basis. Thereafter, significantly displaced lateral wall fractures need to be repaired on timely basis. Proper realignment of the plane of the lateral orbital wall at the sphenozygomatic suture along with the other complex articulations of the zygomatic bone is necessary for proper functional and aesthetic outcome. | 10.1016/j.sjopt.2009.12.003 |
pubmed_644_24251 | OBJECTIVES
To assess efficacy and tolerability of tolterodine extended release (ER) in continent and incontinent subjects with overactive bladder (OAB).
METHODS
This was a post hoc analysis of data from a 12-week, double-blind, placebo-controlled trial of tolterodine ER (4 mg once daily). Subjects completed 7-day bladder diaries at baseline and week 12; those with one or more incontinence episode(s) in their diaries at baseline were considered incontinent. Subjects rated urgency associated with each micturition on a scale from 1 to 5, and micturitions were categorized post hoc by urgency rating as non-OAB (1-2), OAB (3-5), or severe OAB (4-5).
RESULTS
At baseline, 40% of subjects were incontinent. Tolterodine ER (n = 429) reduced total, OAB, and severe OAB micturitions compared with placebo (n = 421) in continent and incontinent subjects. There was no difference between continent and incontinent subjects in terms of the magnitude of improvement with tolterodine ER relative to placebo for total, OAB, and severe OAB micturitions. Reductions in mean urgency and frequency-urgency sum ratings were significantly greater in the tolterodine ER group. Among incontinent subjects, tolterodine ER significantly reduced urgency urinary incontinence episodes and significantly increased the percentage of subjects achieving continence relative to placebo. Adverse event rates were low in both continent and incontinent subjects.
CONCLUSIONS
Tolterodine ER reduced micturitions associated with urgency (OAB or severe OAB) in both continent and incontinent subjects. Tolterodine ER also reduced urgency urinary incontinence episodes in incontinent subjects. These data show that tolterodine ER is effective and well tolerated in both continent and incontinent subjects with OAB. | 10.1016/j.urology.2008.05.019 |
pubmed_416_10038 | The influence of genetic factors on complex phenotypes is context dependent, posing a challenge to quantify the role of single gene variants on this process. Moreover, redundancy and reserve capacity among control systems prevent most physiological stimuli to destabilize these processes. To test whether small gene perturbation can disrupt this equilibrium under pathological conditions, mice harboring one, two, or three copies of the angiotensin converting enzyme (Ace) gene were submitted to 3 and 6 wk of pressure overload (PO). Direct systolic blood pressure (SBP), as an index of cardiac afterload, and left ventricle mass index (LVMI) were measured. LVMI under normotension was the same regardless of the Ace genotype, but the slopes of the LVMI/SBP curves increased in the three- vs. one-copy group by approximately 50% upon 3- or 6-wk PO. Angiotensin II AT1 receptor blocker treatment produced a significant pressure independent decrease in the LVMI/SBP ratio. Unlike the one-copy group, PO resulted in a significant reduction in angiotensinogen and an increase in Ace mRNA expression accompanied by an increase in cardiac angiotensin II levels in the three-copy group. Similarly, the human ACE D gene variant influenced cardiac mass, estimated by Sokolov-Lyon index, in a sample of 1,507 individuals from an urban population only in individuals in the 4th quartile of the blood pressure distribution. Collectively, these data provide direct evidence that ACE gene dosage per se does not influence cardiac mass but upon a pathological stimulus, such as elevation in blood pressure, it modulates cardiac mass in both mice and humans. | 10.1152/physiolgenomics.00023.2006 |
pubmed_995_10709 | The case history of a patient who was treated for Stage IA Hodgkin's disease involving the left supraclavicular region is presented. Shortly after mantle field radiation therapy she developed a mass in the anterior mediastinum. Histological examination of the lesion revealed it to be a benign cyst of the thymus. We consider it important that the possibility of the existence of such a benign growth be considered when a mediastinal mass appears in a patient treated for Hodgkin's disease, before more intensive tumour therapy is given. | 10.1016/s0009-9260(87)80073-9 |
pubmed_960_5362 | A total of 137 patients in a Hamburg dental fears clinic, a majority of them persons with dental phobia, were administered questionnaires regarding dental fears and health-related quality of life. Subjects also underwent a dental examination. Dental fears were shown to be associated with dental health problems. Women were more fearful than men, and younger persons were more fearful than older ones. Patients of lower social economic status had somewhat more dental health problems compared with more economically privileged persons. This study also shows, with the use of the SF-36, that dental fears are negatively related to quality of life, especially as measured in areas such as psychological well-being, vitality, and social functioning. | pubmed_960_5362 |
pubmed_487_2736 | 2-N,N-Dimethylamino-1,3,4-thiadiazole-5-methanesulfonamide was tested for its interaction with the 12 catalytically active mammalian carbonic anhydrase (CA, EC 4.2.1.1) isozymes, CA I-XIV. The compound is a potent inhibitor of CA IV, VII, IX, XII, and XIII (K(I)s of 0.61-39 nM), a medium potency inhibitor of CA II and VA (K(I)s of 121-438 nM), and a weak inhibitor against the other isoforms (CA III, VB, VI, and XIV), making it a very interesting candidate for situations in which a strong/selective inhibition of certain isozymes is needed. The crystal structure of the hCA II adduct of this sulfonamide revealed interesting interactions between the inhibitor and the enzyme which are quite different from those observed in the adducts of CA II with the structurally related aliphatic derivatives zonisamide, 2-amino-1,3,4-thiadiazolyl-5-difluoromethanesulfonamide, and 2-dimethylamino-5-[sulfonamido-(aminomethyl)]-1,3,4-thiadiazole reported earlier. | 10.1016/j.bmcl.2007.12.022 |
pubmed_1136_14528 | Endotoxin including lipopolysaccharide (LPS) confers organ tolerance against subsequent challenge by ischemia and reperfusion (I/R) insult. The mechanisms underlying this powerful adaptive defense remain to be defined. Therefore, in this study we attempted to determine whether nitric oxide (NO) and its associated enzymes, inducible NOS (iNOS) and endothelial NOS (eNOS, a constitutive NOS), are associated with LPS-induced renal tolerance against I/R injury, using iNOS (iNOS knock-out) or eNOS (eNOS knock-out) gene-deleted mice. A systemic low dose of LPS pretreatment protected kidney against I/R injury. LPS treatment increased the activity and expression of iNOS, but not eNOS, in kidney tissue. LPS pretreatment in iNOS, but not eNOS, knock-out mice did not protect kidney against I/R injury. In conclusion, the kidney tolerance to I/R injury conferred by pretreatment with LPS is mediated by increased expression and activation of iNOS. | 10.5483/BMBRep.2010.43.9.629 |
pubmed_741_14678 | Structural and functional homologies have been found among proteins encoded by several retroviral oncogenes, demonstrating the existence of families of these genes. Because the retroviral oncogenes have cellular homologues, the existence of similar families among these 'cellular oncogenes' is also implied (for a review, see ref. 2). Cellular genes belonging to these families have been found in such evolutionarily distant species as humans, fruit flies, nematodes and brewer's yeast (E. Scolnick and S. Reed, personal communications), consistent with the hypothesis that these genes have evolved from a small number of ancestral sequences. We extend these observations by showing here that the proteins encoded by the oncogenes myc, myb and adenovirus E1a are structurally related. Our findings suggest that oncogenes of RNA and DNA tumour viruses may in at least some instances share evolutionary origins and function according to common principles. | 10.1038/306803a0 |
pubmed_1121_8181 | We evaluated health-related quality of life (QoL) and self-reported incomplete adherence as predictors of early second-line antiretroviral (ART) virological failure (VF). ACTG A5273 study participants completed the ACTG SF-21 measure which has 8 QoL domains. We used exact logistic regression to assess the association of QoL at baseline and week 4 with early VF adjusted for self-reported adherence. Of 500 individuals (51% women, median age 39 years) in this analysis, 79% and 75% self-reported complete adherence (no missing doses in the past month) at weeks 4 and 24, respectively. Early VF was experienced by 7% and more common among those who self-reported incomplete adherence. Participants with low week 4 QoL scores had higher rates of early VF than participants with high scores. After adjusting for self-reported adherence at week 4, VL and CD4 at baseline, cognitive functioning, pain and mental health domains were significantly associated with subsequent early VF. In this post-hoc analysis, poorer QoL adds to self-reported incomplete adherence after 4 weeks of second-line ART in predicting VF at week 24. Evaluation is needed to assess whether individuals with poorer QoL might be targeted for greater support to reduce risk of VF.Trial registration: ClinicalTrials.gov identifier: NCT01352715. | 10.1080/09540121.2021.1874275 |
pubmed_269_17921 | BACKGROUND
Cardiovascular surgery is confronted by a lack of suitable materials for patch repair. Acellular animal tissues serve as an abundant source of promising biomaterials. The aim of our study was to explore the bio-integration of decellularized or recellularized pericardial matrices in vivo.
METHODS
Porcine (allograft) and ovine (heterograft, xenograft) pericardia were decellularized using 1% sodium dodecyl sulfate ((1) Allo-decel and (2) Xeno-decel). We used two cell types for pressure-stimulated recellularization in a bioreactor: autologous adipose tissue-derived stromal cells (ASCs) isolated from subcutaneous fat of pigs ((3) Allo-ASC and (4) Xeno-ASC) and allogeneic Wharton's jelly mesenchymal stem cells (WJCs) ((5) Allo-WJC and (6) Xeno-WJC). These six experimental patches were implanted in porcine carotid arteries for one month. For comparison, we also implanted six types of control patches, namely, arterial or venous autografts, expanded polytetrafluoroethylene (ePTFE Propaten® Gore®), polyethylene terephthalate (PET Vascutek®), chemically stabilized bovine pericardium (XenoSure®), and detoxified porcine pericardium (BioIntegral® NoReact®). The grafts were evaluated through the use of flowmetry, angiography, and histological examination.
RESULTS
All grafts were well-integrated and patent with no signs of thrombosis, stenosis, or aneurysm. A histological analysis revealed that the arterial autograft resembled a native artery. All other control and experimental patches developed neo-adventitial inflammation (NAI) and neo-intimal hyperplasia (NIH), and the endothelial lining was present. NAI and NIH were most prominent on XenoSure® and Xeno-decel and least prominent on NoReact®. In xenografts, the degree of NIH developed in the following order: Xeno-decel > Xeno-ASC > Xeno-WJC. NAI and patch resorption increased in Allo-ASC and Xeno-ASC and decreased in Allo-WJC and Xeno-WJC.
CONCLUSIONS
In our setting, pre-implant seeding with ASC or WJC had a modest impact on vascular patch remodeling. However, ASC increased the neo-adventitial inflammatory reaction and patch resorption, suggesting accelerated remodeling. WJC mitigated this response, as well as neo-intimal hyperplasia on xenografts, suggesting immunomodulatory properties. | 10.3390/ijms23063310 |
pubmed_54_3490 | Idiopathic hypereosinophilic syndrome (IHES) is a rare disease that is frequently associated with cardiac thrombosis and endocardial wall thickness. This case report describes 2 patients who had IHES associated with left ventricular (LV) thrombi. The patients' symptoms are atypical. Peripheral blood and bone marrow tests showed markedly elevated eosinophils. Electrocardiography showed ischemic changes in both patients. Negative computed tomography (CT) angiography excluded coronary artery stenosis. Transthoracic echocardiography (TTE), conventional multislice spiral CT, gemstone spectral CT, and cardiac magnetic resonance imaging were used to identify the LV intraluminal thrombus and endocardial thickening, and the diagnostic values of each imaging method were analyzed and compared. These patients were clinically diagnosed as "IHES, LV thrombosis, NYHA heart function classification I." Both patients received oral prednisone and warfarin therapy. At 5 month follow-up, TTE rechecks showed that the size of the LV thrombotic lesion was reduced in the first case but substantially increased in the second case. | 10.1097/MD.0000000000000082 |
pubmed_477_1197 | The ingestion of particles by macrophages leads to the prompt induction of prostaglandin (PG) synthesis. We have now dissected the endocytic process and examined the requirements of prostaglandin E (PGE) synthesis for particle attachment, membrane interiorization, and phagosome-lysosome fusion. Macrophages that were loaded with the polyanion dextran sulfate and exhibited a greater than 99% inhibition of phagosome-lysosome fusion produced normal amounts of PGE upon challenge with zymosan. Inhibition of membrane interiorization with cytochalasin D was similarly ineffective in blocking PGE synthesis. The addition of large numbers of unmodified polystyrene latex beads, which were readily ingested by macrophages, failed to stimulate PGE synthesis. However, when macrophages were challenged with latex beads coated with immune complexes, an increased synthesis of PGE resulted. No response occurred if the complex was prepared with the F(ab')2 fragment of IgG. Similar results occurred when nonphagocytizable Sephadex beads coated with immune complexes were employed. We conclude that particle binding to the Fc receptor of the macrophage plasma membrane is a sufficient stimulus for PGE synthesis. | 10.1073/pnas.77.7.4279 |
pubmed_848_12827 | In an attempt to generate a bicyclic 5,8-ethano derivative of N-methylmorphinan, an isomeric bicyclic hexahydroaporphine 2 was synthesized. The phenolic analogue of 2 has demonstrated affinity for mu opioid receptors in vitro and, along with 2, provided weak, primarily nonopioid analgesic action when injected intracerebroventricularly in mice. It was of interest to assess the potential opioid antagonist action of bicyclic hexahydroaporphine analogues containing cyclopropylmethyl and allyl nitrogen substituents. As the first steps in the generation of these potential opioid antagonists, the secondary bicyclic hexahydroaporphine 3 and its N-cyclopropylmethyl congener 4 were synthesized. N-Demethylation of 2 was initially attempted via the von Braun reaction, but acid-catalyzed hydrolysis of the crude N-cyano intermediate resulted in product decomposition. A successful approach to 3 involved the hydrolysis of the N-formyl precursor 1 in ethanolic potassium hydroxide. Direct alkylation of the secondary amine 3 utilizing cyclopropylmethyl bromide and sodium bicarbonate successfully generated the alkylated derivative 4. Both products were purified in hydrochloride salt form and characterized by standard analytical and spectroscopic methods. The free base form of 3 was highly sensitive to photooxidation. Opioids are known to oxidize to 10-keto structures, and secondary amines can oxidize to hydroxylamines. Infrared analysis of the decomposition product indicated the presence of both hydroxy and carbonyl groups which were absent in the spectrum of the salt. Structures of potential oxidation products are proposed. | 10.1002/jps.2600791119 |
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