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pubmed_1031_10957 | Predicting the long-time, nonequilibrium dynamics of receptor-ligand interactions for structured proteins in a host fluid is a formidable task, but of great importance to predicting and analyzing cell-signaling processes and small molecule drug efficacies. Such processes take place on timescales on the order of milliseconds to seconds, so "brute-force" real-time, molecular or atomic simulations to determine absolute ligand-binding rates to receptor targets and over a statistical ensemble of systems are not currently feasible. In the current study, we implement on real protein systems a previously developed 3-5 hybrid molecular dynamics/Brownian dynamics algorithm, which takes advantage of the underlying, disparate timescales involved and overcomes the limitations of brute-force approaches. The algorithm is based on a multiple timescale analysis of the total system Hamiltonian, including all atomic and molecular structure information for the system: water, ligand, and receptor. In general, the method can account for the complex hydrodynamic, translational-orientational diffusion aspects of ligand-docking dynamics as well as predict the actual or absolute rates of ligand binding. To test some of the underlying features of the method, simulations were conducted here for an artificially constructed spherical protein "made" from the real protein insulin. Excellent comparisons of simulation calculations of the so-called grand particle friction tensor to analytical values were obtained for this system when protein charge effects were neglected. When protein charges were included, we found anomalous results caused by the alteration of the spatial, microscopic structure of water proximal to the protein surface. Protein charge effects were found to be highly significant and consistent with the recent hypothesis of Hoppert and Mayer (Am Sci 1999;87:518-525) for charged macromolecules in water, which involves the formation of a "water dense region" proximal to the charged protein surface followed by a "dilute water region." We further studied the algorithm on a D-peptide/HIV capside protein system and demonstrated the algorithms utility to study the nonequilibrium docking dynamics in this contemporary problem. In general, protein charge effects, which alter water structural properties in an anomalous fashion proximal to the protein surface, were found to be much more important than the so-called hydrodynamic interaction effects between ligand and receptor. The diminished role of hydrodynamic interactions in protein systems allows for a much simpler overall dynamic algorithm for the nonequilibrium protein-docking process. Further studies are now underway to critically examine this simpler overall algorithm in analyzing the nonequilibrium protein-docking problem. | 10.1002/prot.10411 |
pubmed_730_15833 | The numbers of participants over 75 years of age in previous studies of oral health have not been sufficient to permit a full investigation of the influence of age on the mouth. In this study a disproportionate stratified random sample of 255 independent elders was selected from a list of urban voters to provide similar numbers of men and women in three age groups. The subjects were interviewed and examined, and nearly half of them had mucosal disorders. There was a significant (P < 0.05) association between mucosal lesions and the use of dentures and tobacco, whereas stomatitis, denture-related hyperplasia and angular cheilitis in particular were associated significantly with men and with the use of defective dentures. Logistic regression revealed that neither age alone nor the quality of dentures predispose to mucosal lesions, but that the odds of finding stomatitis, denture-related hyperplasia and angular cheilitis in particular increased about three-fold in denture-users, and almost doubled in men. | 10.1111/j.1601-0825.1998.tb00252.x |
pubmed_313_12631 | AIMS
Left bundle branch block (LBBB) is induced in approximately one-third of all transcatheter aortic valve implantation (TAVI) procedures. We investigated electrophysiological remodelling in patients with TAVI-induced LBBB.
METHODS AND RESULTS
This retrospective study comprises 107 patients with initially narrow QRS complex of whom 40 did not and 67 did develop persistent LBBB after TAVI. 12-lead electrocardiograms (ECGs) taken before TAVI, within 24 hours ('acute'), and 1-12 months after TAVI ('chronic') were used to reconstruct vectorcardiograms. From these vectorcardiograms, QRS and T-wave area were calculated as comprehensive indices of depolarization and repolarization abnormalities, respectively. TAVI-induced LBBB resulted in significant acute depolarization and repolarization changes while further repolarization changes were observed with longer lasting LBBB. The amount of long-term repolarization changes (remodelling) was highly variable between patients. The change in T-wave area between acute and chronic LBBB ranged from +57% to - 77%. After dividing the LBBB cohort into tertiles based on the change in T-wave area, only baseline QRS area was larger in the tertile with no significant change in T-wave area. During longer lasting LBBB, the spatial vector gradient (SVG) changed orientation towards the direction of the QRS-vector, indicating that later-activated regions developed shorter action potential duration.
CONCLUSION
This study in patients with TAVI-induced LBBB shows that repolarization changes develop within months after onset of LBBB, and that these changes are highly variable between individual patients. | 10.1093/europace/euw350 |
pubmed_548_14876 | INTRODUCTION
The proximal attachment of hamstring muscles has a very high incidence of injuries due to a wide number of factors and its morphology may be one of the underlying factors as scientific literature points out. The connective tissue component of the attachment of hamstring muscles is not well known. For this reason the aim of this study is to describe the anatomy and histology surrounding the proximal attachment of the hamstring muscles (PAHM) and its direct anatomic relations.
METHODS
Forty-eight cryopreserved lower limbs have sequentially been studied by means of dissection, anatomical sections and histology.
RESULTS
All specimens studied presented an annular connective tissue structure that resembles a retinaculum, which covers and adapts to the attachment of hamstring muscles on the ischial tuberosity.
CONCLUSION
The results show how this retinaculum is continuous with the long head of biceps femoris muscle, however there is a layer of loose connective tissue between the retinaculum and the semitendinosus muscle. Furthermore, this structure receives expansions of the anterior epimysium of the gluteus maximus muscle (GIM). | pubmed_548_14876 |
pubmed_417_10940 | Schwann cells support and facilitate axonal growth during development and successful regeneration in the peripheral nerve. In the regenerating rat sciatic nerve, Schwann cells provide a trophic milieu for primary sensory, sympathetic, and motoneurons. We have characterized a neurotrophic activity produced by adult rat sciatic nerve Schwann cells and a spontaneously immortal Schwann cell clone (iSC). This activity elicits neurite outgrowth from chick embryo explants of both CNS and PNS. The iSC activity has been concentrated by cation-exchange chromatography and compared to known neurotrophins in bioassay. Pooled bound fractions elicit neurite outgrowth from sympathetic, ciliary and motoneurons. In collagen matrix cocultures of iSC and E4 ventral horn (before motor axon extension to muscle targets), the iSC activity can direct the initial axonal extension from motoneurons. The data presented suggest that Schwann cell-produced activity may mediate motoneuron axonal extension before contact with their peripheral source of neurotrophin. | 10.1002/jnr.490370105 |
pubmed_1098_18181 | In the rapidly changing moisture air, conventional relative humidity (RH) sensors are often difficult to respond in time and accurately due to the limitation of flow rate and non-uniform airflow distribution. In this study, we numerically demonstrate that humidity changes on micro-zones can be monitored in real time using a Bloch surface wave (BSW) ubiquitous in one-dimensional photonic crystals (1DPC). This phenomenon can be observed by leakage radiation microscope (LRM). After theoretically deriving the angular resolution limit of LRM, we obtained the minimum BSW angular change on a practical scheme that can be observed in the momentum space to complete the detection, and realized the dynamic real-time monitoring of small-scale humidity change in experiment for the first time. This monitoring method has extremely high figure of merit (FOM) without hysteresis, which can be used in humidity sensing and refractive index sensing as well as the research on turbulence. | 10.1364/OE.465736 |
pubmed_238_22397 | The main two functions of the lung are the respiratory functions, dependent on ventilatory mechanics and gas exchange, and the nonrespiratory functions such as metabolic, immunological, and endocrine ones. Lung aging is secondary to the age-dependent impairment of one or more of these functions. Tobacco use accelerates lung aging and touches biological, structural and respiratory and non-respiratory functions. These changes contribute to the development of chronic pulmonary diseases and predispose to pulmonary infections in older individuals. The knowledge of these changes is very useful for better management of elderly. Lung health in aging can be improved by strategies that slow the age-related decline in lung function by acting on the environmental parameters. It is also possible to improve lung development in children and to strengthen the lungs' resistance to environmental challenges and thus to extrinsic lung aging. | pubmed_238_22397 |
pubmed_11_17701 | Male, 76 year-old patient with a history of total hip arthroplasty who presents with a mass in the iliac fossa with swelling of the thigh and hip pain upon flexion and extension. Complementary ultrasound and computed tomography scan studies show a giant lobulated cystic mass in the left iliac fossa, 7 cm in diameter, near the prosthesis. Cyst formation caused by polyethylene disease after total hip arthroplasty is infrequent. We present a case of large psoas bursitis secondary to the release of polyethylene particles which caused superficial femoral vein compression and thrombosis. | pubmed_11_17701 |
pubmed_773_9655 | The reported growth-promoting effects of the beta-sympathomimetic compound, ritodrine, have been investigated. The carbohydrate tolerance of eight pregnant women was found to be unaffected by treatment with oral ritodrine over a ten-week period. A further observation that the carbohydrate metabolism of the newborn infants of these women was within normal limits tends to discount possibility that any growth-promoting action ritodrine may have on the fetus is mediated through a diabetogenic effect on the mother. | 10.1111/j.1471-0528.1976.tb00918.x |
pubmed_16_11116 | BACKGROUND
Research is needed about the usage of complementary and alternative medicines within culturally diverse groups because of a growing number of people who use these remedies.
OBJECTIVE
To understand the prevalence and predictors of Traditional Chinese Medicine (TCM) use by older Chinese immigrants in Canada.
METHODS
This is based on the data collected from a representative sample of 2167 elderly Chinese immigrants aged 55 years and above in seven Canadian cities. Logistic regression was used to estimate the probability of using TCM in combination with Western health services (WHS). Use of Chinese herbs, herbal formulas, and TCM practitioners (herbalists) was predicted, based upon the effects of predisposing, enabling and need factors.
RESULTS
The response rate was 77%. Over two-thirds of the older Chinese immigrants reported using TCM in combination with WHS. About half (50.3%) of the older Chinese immigrants used Chinese herbs, 48.7% used Chinese herbal formulas, and 23.8% consulted a Chinese herbalist. Although separate analysis was conducted, similar predictors were identified. Country of origin, Chinese health beliefs, social support, city of residency, and health variables were the common predictors of using a form of TCM.
CONCLUSION
The combined use of TCM and WHS is common among elderly Chinese immigrants. Culture-related variables are important in determining use of TCM. The predictors identified should help physicians to recognize who among the elderly Chinese immigrants are more likely to use TCM so that a more in-depth understanding toward their health practices and needs can be achieved. | 10.1093/fampra/cml058 |
pubmed_625_19255 | The hepatitis E virus- (HEV-) helicase as a novel drug-target was evaluated. While cell culture model was used for mutational characterization of helicase, in silico protein modeling and virtual screening were employed to identify helicase inhibitors. None of the saturation mutant replicons significantly affected RNA replication. Notably, mutants encompassing the Walker motifs replicated as wild-type, showing indispensability of nucleotides conservation in viability compared to known criticality of amino acids. A 3D modeling of HEV-helicase and screening of a compound dataset identified ten most promising inhibitors with drug likeness, notably, JFD02650, RDR03130, and HTS11136 that interacted with Walker A residues Gly975, Gly978, Ser979, and Gly980. Our model building and virtual identification of novel helicase inhibitors warrant further studies towards developing anti-HEV drugs. | 10.1155/2018/5753804 |
pubmed_1113_16541 | Chaotic orbits of the mushroom billiards display intermittent behaviors. We investigate statistical properties of this system by constructing an infinite partition on the chaotic part of a Poincaré surface, which illustrates details of chaotic dynamics. Each piece of the infinite partition has a unique escape time from the half disk region, and from this result it is shown that, for fixed values of the system parameters, the escape time distribution obeys a power law 1/t(esc)(3). | 10.1103/PhysRevE.75.066215 |
pubmed_36_20358 | OBJECTIVE
Recent evidence suggests that symptoms of social impairment in autism spectrum disorder (ASD) form a spectrum that extends into the general population. However, it is unclear whether the neuroanatomy of ASD also shows a similar continuum in the general population. Therefore, the goal of the present study was to investigate the relationship between cortical morphology and autistic traits along a continuum in a large population-based sample of young children.
METHOD
The study included 717 children, aged 6-10 years, who are participants in the Generation R Study, a large population-based cohort. Autistic traits were measured using the Social Responsiveness Scale when the children were approximately 6 years old. High-resolution MRI was obtained, and morphological measures of the cortex, including cortical thickness and gyrification, were quantified brain-wide.
RESULTS
Children with more autistic traits showed widespread areas of decreased gyrification. After excluding children with the highest autistic traits and confirmed ASD, the association remained present in a large cluster involving the left hemisphere temporal and precuneus regions. Comparable, but nonsignificant, effects when comparing a small sample of confirmed ASD case subjects with age- and gender-matched control subjects were observed.
CONCLUSIONS
Differences in cortical morphology related to autistic traits along a continuum in a large population-based sample of school-aged children were found. Part of these differences remained after excluding the most severely affected children. These findings lend support to an extension of the neurobiology of autistic traits to the general population. | 10.1176/appi.ajp.2014.14040482 |
pubmed_661_13634 | Chlamydia trachomatis can cause many kinds of diseases in humans, both men and women. Its diagnosis depends on the observation of intracytoplasmic inclusion bodies on smears. To observe intracytoplasmic inclusion bodies we applied the Papanicolaou and immunocytochemical techniques. Elementary and reticulate bodies were seen more easily using the immunocytochemical technique in 3 hours on gynecological and urethral specimens. The immunocytochemical technique is rapid, accurate and specific with unstained gynecological and urethral specimens as well as destained Papanicolaou smears. It appears that fixation is the most important factor in immunocytochemical observations of Chlamydia. Absolute methanol or ethanol was the fixation agent of choice based on our experience. After proper fixation, the immunocytochemical technique can be applied for routine examinations to detect Chlamydia trachomatis. | pubmed_661_13634 |
pubmed_150_1608 | WHAT IS KNOWN AND OBJECTIVES
Choosing an alternative statin is recommended when managing statin-associated muscle symptoms (SAMS) and new hydrophilic statins are often suggested. We report on a case of statin-associated muscle damage that was successfully managed by simplifying the patient's combination therapy with simvastatin-ezetimibe to simvastatin alone.
CASE SUMMARY
The patient experienced SAMS when he was successively treated with atorvastatin, rosuvastatin, Xuezhikang capsule and combined simvastatin/ezetimibe therapy. However, the patient tolerated simvastatin therapy well even at a dose of 40 mg/day.
WHAT IS NEW AND CONCLUSION
Our case suggests that patients with SAMS who are intolerant to a wide variety of statins may be successfully managed with simvastatin monotherapy. | 10.1111/jcpt.12419 |
pubmed_212_918 | A 37-year-old man, who had been undergoing hemodialysis for nine years, had severe osteodystrophy with a consequent 28-cm locc in height. This shrinkage in size is probably secondary to tertiary hyperparathyroidism. In spite of two previous explorations, there is still evidence of hyperparathyroidism and his present condition precludes surgical intervention. | 10.1001/jama.244.3.267 |
pubmed_343_9789 | We aimed to investigate the early changes in ammonia levels and liver function in patients with advanced hepatocellular carcinoma treated with lenvatinib. This retrospective study included 23 patients with advanced hepatocellular carcinoma who were able to receive lenvatinib continuously for at least 1 week. We compared their ammonia levels (NH3), total bilirubin (Bil), albumin, and prothrombin (PT) activity at before and after 1 week of lenvatinib administration, and additionally, compared the 2 groups which were divided based on the presence/absence of portosystemic collaterals (PSCs). Before administration of lenvatinib the patients with PSCs had significantly worse ammonia levels and liver function than the patients without PSCs (NH3: P = 0.013, Bil: P = 0.004, PT: P = 0.047, respectively). Moreover, the indices were worse in all the patients after 1 week of lenvatinib than before administration (NH3: P = 0.001, Bil: P = 0.025, PT: P < 0.001, respectively). Moreover, the changes in ammonia levels were investigated for 4 weeks. The ammonia level increased, to peak at 2 weeks, but decreased after 3 weeks. None of the patients discontinued lenvatinib therapy because of an adverse event. The ammonia levels of the study patients increased from baseline at 1 week after lenvatinib administration, but therapy could be continued for 4 weeks by appropriate management. | 10.1038/s41598-019-48045-z |
pubmed_511_6915 | Thrombotic microangiopathy (TMA) arises in a variety of clinical circumstances with the potential to cause significant dysfunction of the kidneys, brain, gastrointestinal tract and heart. TMA should be considered in all patients with thrombocytopenia and anaemia, with an immediate request to the haematology laboratory to look for red cell fragments on a blood film. Although TMA of any aetiology generally demands prompt treatment, this is especially so in thrombotic thrombocytopenic purpura (TTP) and atypical haemolytic uraemic syndrome (aHUS), where organ failure may be precipitous, irreversible and fatal. In all adults, urgent, empirical plasma exchange (PE) should be started within 4-8 h of presentation for a possible diagnosis of TTP, pending a result for ADAMTS13 (a disintegrin and metalloprotease thrombospondin, number 13) activity. A sodium citrate plasma sample should be collected for ADAMTS13 testing prior to any plasma therapy. In children, Shiga toxin-associated haemolytic uraemic syndrome due to infection with Escherichia coli (STEC-HUS) is the commonest cause of TMA, and is managed supportively. If TTP and STEC-HUS have been excluded, a diagnosis of aHUS should be considered, for which treatment is with the monoclonal complement C5 inhibitor, eculizumab. Although early confirmation of aHUS is often not possible, except in the minority of patients in whom auto-antibodies against factor H are identified, genetic testing ultimately reveals a complement-related mutation in a significant proportion of aHUS cases. The presence of other TMA-associated conditions (e.g. infection, pregnancy/postpartum and malignant hypertension) does not exclude TTP or aHUS as the underlying cause of TMA. | 10.1111/imj.13804 |
pubmed_1140_13188 | OBJECTIVE
To investigate the nutrient effect of glutamine on small intestinal repair in weanling rats after chronic diarrhea.
METHODS
Forty 21-day-old wistar rats were randomly divided into five groups (8 in each). Animal model of chronic diarrhea was induced by a lactose enriched diet in the weanling Wistar rat, normal control group was fed with a standard semipurified diet, and after 14 days the rats in both groups were killed to test the establishment of the model. After the establishment of the model, the other groups were fed with the standard semipurified diet to recover for 7 days, and were randomly divided into three groups: non-intervention group, glutamine (Gln)-intervention group and control group. Glutamine concentrations in blood was detected by high-performance liquid chromatography (HPLC). Morphological changes including villus height and villus surface area of the jejunum were measured under a light microscope and electron microscope, expression of proliferating cell nuclear antigen (PCNA) as an index of cell proliferation was observed using immunohistochemical staining and image analysis.
RESULTS
The diarrhea rate in model group was 100 percent, average diarrhea index was 1.16 +/- 0.06, but both diarrhea rate and average diarrhea index in control group were 0 (P < 0.01), which affirmed establishment of the model. There was significant decrease of body weight, plasma Gln concentration, villus height, villus surface area and expression of PCNA in non-intervened group compared with the control group (P < 0.01). There was still significant decrease of body weight, villus height and villus surface area in Gln-intervened group compared with control group (P < 0.01), but plasma Gln concentration and expression of PCNA in Gln-intervened group had recovered to normal (P > 0.05). And compared with non-intervened group, except for body weight (P > 0.05), plasma glutamine, villus height, villus surface area and expression of PCNA were all significantly increased in Gln-intervened group.
CONCLUSION
Chronic diarrhea can induce malnutrition and reduce the villus height, villus surface area, expression of PCNA and plasm glutamine concentration. Oral glutamine could improve the proliferation of crypt cell and promote repair of intestinal mucosa after chronic diarrhea. | pubmed_1140_13188 |
pubmed_822_7595 | BACKGROUND
Population genetics predicts that tight linkage between new and/or pre-existing beneficial and deleterious alleles should decrease the efficiency of natural selection in finite populations. By decoupling beneficial and deleterious alleles and facilitating the combination of beneficial alleles, recombination accelerates the formation of high-fitness genotypes. This may impose indirect selection for increased recombination. Despite the progress in theoretical understanding, interplay between recombination and selection remains a controversial issue in evolutionary biology. Even less satisfactory is the situation with crossover interference, which is a deviation of double-crossover frequency in a pair of adjacent intervals from the product of recombination rates in the two intervals expected on the assumption of crossover independence. Here, we report substantial changes in recombination and interference in three long-term directional selection experiments with Drosophila melanogaster: for desiccation (~50 generations), hypoxia, and hyperoxia tolerance (>200 generations each).
RESULTS
For all three experiments, we found a high interval-specific increase of recombination frequencies in selection lines (up to 40-50% per interval) compared to the control lines. We also discovered a profound effect of selection on interference as expressed by an increased frequency of double crossovers in selection lines. Our results show that changes in interference are not necessarily coupled with increased recombination.
CONCLUSIONS
Our results support the theoretical predictions that adaptation to a new environment can promote evolution toward higher recombination. Moreover, this is the first evidence of selection for different recombination-unrelated traits potentially leading, not only to evolution toward increased crossover rates, but also to changes in crossover interference, one of the fundamental features of recombination. | 10.1186/s12915-015-0206-5 |
pubmed_120_13270 | Post-myocardial infarction left ventricular pseudoaneurysm resulting from free wall rupture is a rare finding and its recognition during life is uncommon. The diagnosis is difficult since symptoms, clinical evaluation and electrocardiographic and X-ray findings are usually non-specific. We herein present a case of a pseudoaneurysm manifesting after a silent myocardial infarction and diagnosed at echocardiography in a patient who, at the time of hospitalization, had a history and clinical and laboratory findings suggestive of pulmonary embolism. The patient was successfully operated. The present report underlines the diagnostic and prognostic value of two-dimensional transthoracic echocardiography. The clinical and laboratory findings are also discussed in the light of the recent literature. | pubmed_120_13270 |
pubmed_443_6818 | Cyclin-dependent kinase (CDK) inhibitor genes have recently been proposed as new tumor suppressor genes. To define the possible participation of CDK inhibitor genes in lung carcinogenesis, we investigated the alterations of p15INK4B, p16INK4A, p21Waf1, and p27Kip1 genes in 34 human lung cancer cell lines using the polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP), direct sequencing, and southern dot blot methods. Among the four CDK inhibitor genes, alterations of only the p16INK4A gene were found in 8 out of 34 (24%) cell lines, and all eight cell lines having a p16INK4A gene alteration had an alteration of either the K-ras of p53 gene. Conversely, p16INK4A gene alterations were found in none of the 3 cell lines having Rb gene alterations and none of the 3 cell lines having amplification of the N-myc gene. Polymorphism was found in both p21Waf1 and p27Kip1 genes, but no association was found between the polymorphism and alterations of other genes. These results suggest that p16INK4A gene alterations may play a certain role for lung carcinogenesis in co-operation with either K-ras or p53 gene alterations. | pubmed_443_6818 |
pubmed_492_18757 | OBJECTIVE
To explore the predictive value of MRI parameters and tumour characteristics before neoadjuvant chemotherapy (NAC) and to compare changes in tumour size and tumour apparent diffusion coefficient (ADC) during treatment, between patients who achieved pathological complete response (pCR) and those who did not.
METHODS
Approval by the Regional Ethics Committee and written informed consent were obtained. Thirty-one patients with invasive breast carcinoma scheduled for NAC were enrolled (mean age, 50.7; range, 37-72). Study design included MRI before treatment (Tp0), after four cycles of NAC (Tp1) and before surgery (Tp2). Data in pCR versus non-pCR groups were compared and cut-off values for pCR prediction were evaluated.
RESULTS
Before NAC, HER2 overexpression was the single significant predictor of pCR (p = 0.006). At Tp1 ADC, tumour size and changes in tumour size were all significantly different in the pCR and non-pCR groups. Using 1.42 × 10(-3) mm(2)/s as the cut-off value for ADC, pCR was predicted with sensitivity and specificity of 88% and 80%, respectively. Using a cut-off value of 83% for tumour volume reduction, sensitivity and specificity for pCR were 91% and 80%.
CONCLUSION
ADC, tumour size and tumour size reduction at Tp1 were strong independent predictors of pCR. | 10.1007/s00330-010-2020-3 |
pubmed_2_11142 | BACKGROUND
Current tissue-engineered cartilage constructs contain insufficient amounts of collagen, whose function is to resist tension. We postulate that dynamic tension is necessary to stimulate collagen formation. Another shortcoming is that tissue-engineered cartilage does not possess native zonal variations. We hypothesize that applying depth-varying mechanical cues would stimulate extracellular matrix (ECM) synthesis depth dependently. We developed a dedicated loading regime called sliding indentation, which enables us to apply dynamic tension as well as depth-varying strain fields to the chondrocyte-seeded agarose constructs.
OBJECTIVE
In 2 study designs, we explored whether sliding indentation would increase collagen content and induce depth-varying ECM distribution.
METHODS
In the first study, we developed an agarose-sandwich model that involves embedding of a thin chondrocyte-seeded 0.5% agarose layer between two cell-free 3% agarose layers. In the second study, 3-mm-thick chondrocyte-seeded agarose constructs were created. Sliding indentation at 10% depth and 1 Hz was applied to constructs in both studies for 4 h/day during 28 days, and unloaded constructs served as control.
RESULTS
Sliding indentation resulted in an increased amount of collagen in the produced cartilage layer. Further, sliding indentation for 7 days resulted in a depth-dependent response at gene expression levels, with the highest response in the regions that received highest strains. Analysis of protein expression after 28 days showed a similar depth-dependent distribution in all constructs, which further enhanced by sliding indentation.
CONCLUSIONS
Sliding indentation can increase collagen content and enhances depth-dependent ECM distribution, and is therefore a promising strategy for culturing cartilage with improved properties. | 10.1089/ten.TEA.2012.0688 |
pubmed_386_17239 | The extracellular matrix (ECM) is a major constituent of the vessel wall. In addition to providing a structural scaffold, the ECM controls numerous cellular functions in both physiologic and pathologic settings. Vascular remodeling occurs after injury and is characterized by endothelial cell activation, inflammatory cell infiltration, phenotypic modulation of smooth muscle cells (SMCs), and augmented deposition of collagen-rich ECM. R1R2, a peptide derived from the bacterial adhesin SFS, with sequence homology to collagen, is known to inhibit collagen type I deposition in vitro by inhibiting the binding of fibronectin to collagen. However, the inhibitory effects of R1R2 during vascular remodeling have not been explored. We periadventitially delivered R1R2 to carotid arteries using pluronic gel in a vascular remodeling mouse model induced by blood flow cessation, and evaluated its effects on intima-media thickening, ECM deposition, SMC activation, and inflammatory cell infiltration. Morphometric analysis demonstrated that R1R2 reduced intima-media thickening compared to the control groups. R1R2 treatment also decreased collagen type I deposition in the vessel wall, and maintained SMC in the contractile phenotype. Interestingly, R1R2 dramatically reduced inflammatory cell infiltration into the vessel by ∼ 78%. This decrease was accompanied by decreased VCAM-1 and ICAM-1 expression. Our in vitro studies revealed that R1R2 attenuated SMC proliferation and migration, and also decreased monocyte adhesion and transendothelial migration through endothelial cells. Together, these data suggest that R1R2 attenuates vascular remodeling responses by decreasing inflammation and by modulating SMC proliferation and migration, and suggest that the R1R2 peptide may have therapeutic potential in treating occlusive vascular diseases. | 10.1371/journal.pone.0117356 |
pubmed_351_12605 | Ner protein of bacteriophage Mu, produced by recombinant DNA techniques in Escherichia coli, has been found to possess a molecule of pyruvic acid attached covalently through carbon-2 to the amino-terminal cysteine residue. The intact protein and the amino-terminal chymotryptic peptide were found by mass spectrometry to be 70 mass units heavier than expected. The modified peptide was unstable under mildly acid or mildly basic conditions. Two-dimensional nuclear magnetic resonance spectroscopy of the modified and unmodified forms of the amino-terminal chymotryptic peptide was consistent with the presence of pyruvate linked through carbon-2 to the amino-terminal Cys residue. Treatment of the modified form with 2,4-dinitrophenylhydrazine in acid medium led to the expected hydrazone of pyruvic acid, which was identified by high pressure liquid chromatography. Of the two proteins known to be modified by pyruvate through its central carbon (the other being human adult hemoglobin, in which the modified form represents only a very minor fraction), Ner is the first protein found to be modified quantitatively. Given the instability of the modification, it may be more prevalent than recognized hitherto. Incubation with 2,4-dinitrophenylhydrazine may offer a useful means of detecting the presence of pyruvate linked to proteins in this way. | pubmed_351_12605 |
pubmed_629_9405 | P300-based GKT (guilty knowledge test) has been suggested as an alternative approach for conventional polygraphy. The purpose of this study is to evaluate three classifying methods for this approach and compare their performances in a lab analogue. Several subjects went through the designed GKT paradigm and their respective brain signals were recorded. For the analysis of signals, BAD (bootstrapped amplitude difference) and BCD (bootstrapped correlation difference) methods as two predefined methods alongside a new approach consisting of wavelet features and a statistical classifier were implemented. The rates of correct detection in guilty and innocent subjects were 74-80%. The results indicate the potential of P300-based GKT for detecting concealed information, although further research is required to increase its accuracy and precision and evaluating its vulnerability to countermeasures. | 10.1016/j.ijpsycho.2006.05.009 |
pubmed_1052_20594 | We demonstrate, for the first time, an electrochemical sensor that provides antipodal signals upon application of square wave voltammetry (SWV), for enantioselective recognition of 3,4-dihydroxyphenylalanine based on chiral single-walled carbon nanotubes (SWCNTs) in the presence of sulphuric acid. Interestingly, the enantioselectivity was not observed using the common method of cyclic voltammetry (CV) but the SWV peak currents of enantiomers were found to be quite different and hence the enantiomers could be successfully recognized. Moreover, the antipodal signals provided by two SWV scan modes offer the possibility for results to be confirmed mutually, showing a great practical value and analytical application prospects. | 10.1039/c4an00098f |
pubmed_916_4648 | BACKGROUND AND OBJECTIVE
Vitamin E has been suggested as nutritional intervention for the prevention of degenerative and age-related diseases. In this study, we aimed to elucidate the underlying mechanism of tocotrienol-rich fraction (TRF) in delaying cellular aging by targeting the proliferation signaling pathways in human diploid fibroblasts (HDFs).
MATERIALS AND METHODS
Tocotrienol-rich fraction was used to treat different stages of cellular aging of primary human diploid fibroblasts viz. young (passage 6), pre-senescent (passage 15) and senescent (passage 30). Several selected targets involved in the downstream of PI3K/AKT and RAF/MEK/ERK pathways were compared in total RNA and protein.
RESULTS
Different transcriptional profiles were observed in young, pre-senescent and senescent HDFs, in which cellular aging increased AKT, FOXO3, CDKN1A and RSK1 mRNA expression level, but decreased ELK1, FOS and SIRT1 mRNA expression level. With tocotrienol-rich fraction treatment, gene expression of AKT, FOXO3, ERK and RSK1 mRNA was decreased in senescent cells, but not in young cells. The three down-regulated mRNA in cellular aging, ELK1, FOS and SIRT1, were increased with tocotrienol-rich fraction treatment. Expression of FOXO3 and P21Cip1 proteins showed up-regulation in senescent cells but tocotrienol-rich fraction only decreased P21Cip1 protein expression in senescent cells.
CONCLUSIONS
Tocotrienol-rich fraction exerts gene modulating properties that might be responsible in promoting cell cycle progression during cellular aging. | 10.7417/CT.2015.1825 |
pubmed_969_19135 | A novel immunosuppressive compound, FK-506, isolated from Streptomyces has potent immunosuppressive activities. To investigate the effect of FK-506 on the course of diabetes in nonobese diabetic (NOD) mice, we gave this drug to these animals, from the age of 8 weeks, intraperitoneally, in doses of 0.1 mg (2.5 mg/kg/day) or 0.01 mg (0.25 mg/kg/day) three times a week. Overt diabetes were observed in 75.5% of control mice by the age of 20 weeks. In contrast, no diabetes occurred in mice given 0.1 mg of FK-506. Sixteen percent of mice treated with 0.01 mg of the drug became diabetic. Administration of this drug prevented the progression of insulitis in NOD mice. The mice given 0.1 mg of FK-506 lost weight, but this was reversible. | 10.1016/0090-1229(90)90041-n |
pubmed_584_6268 | Chronic hypoxia activates a local angiotensin-generating system in the carotid body. Here, we test the hypothesis that the activity of the critical enzyme for this system, angiotensin-converting enzyme (ACE), in the carotid body is subject to regulation by a time-course hypoxia. Results from the carotid body assays showed that ACE activity was markedly increased under the hypoxic stress of 7-, 14-, 21-, and 28-day exposures. The changes in ACE activity of 7-day (15.00 vs. 30.95 x 10(-5) nmol.microg(-1).min(-1)), 14-day (8.73 vs. 30.25 x 10(-5) nmol.microg(-1).min(-1)), and 21-day (11.41 vs. 31.83 x 10(-5) nmol.microg(-1).min(-1)) hypoxia treatments were enhanced significantly. However, ACE activity in 28-day (13.18 vs. 24.53 x 10(-5) nmol.microg(-1).min(-1)) hypoxia treatment was observed to increase insignificantly when compared with results in the respective control groups. Captopril inhibited all rises in ACE activity in both the control and experimental groups. Results clearly indicate an activation of the enzymatic activity of ACE, the critical enzyme for determining the conversion of angiotensin I into the physiologically active angiotensin II, by chronic hypoxia in the carotid body. An increase in the ACE activity may increase the local production of angiotensin II in the carotid body and thus its agonist action at the AT1 receptor. This may be important in the modulation of cardiopulmonary adaptation in the hypoxic ventilatory response as well as for electrolyte and water homeostasis during chronic hypoxia. | 10.1152/japplphysiol.00684.2003 |
pubmed_709_9085 | Ninety-two patients with histologically confirmed bronchogenic carcinoma treated by surgical resection of the tumour were subsequently given immunotherapy with BCG (Glaxo). The patients were randomly allocated into three groups. Twenty-nine patients received multipuncture BCG (50 to 250 X 10(6) viable units), and twenty-six patients intradermal BCG (0.4 to 0.9 X 10(6) viable units), treatment being given at 1, 2, 6, 9, 13, 26, and 52 weeks after operation. Thirty-seven control patients did not receive any BCG immunotherapy; two patients in the control group were lost to follow-up. The overall five-year survival in all groups was 37%. Favourable prognostic features were squamous carcinoma (45% five-year survival), the absence of involved mediastinal nodes at operation (46%), and lobectomy (45%), but even the presence of involved mediastinal nodes was associated with a 19% five-year survival. There were no statistically significant differences between the survival of the control group and either group treated by immunotherapy considered individually or in combination. The influence of the presence of positive mediastinal lymph nodes and the extent of surgical resection on survival was not affected by immunotherapy. No serious side-effects of immunotherapy were encountered. | 10.1136/thx.37.1.57 |
pubmed_370_11155 | 1. A dye-linked methanol dehydrogenase, resembling many others from a variety of methylotrophic bacteria, was purified to homogeneity from extracts of methanol-grown Methylophilus methylotrophus. 2. The enzyme was very stable in the presence of methanol; in the absence of methanol it had a half-life of 1-2 days at 4 degrees C. 3. The value of A1% 1cm,280 was 17.5. 4. The enzyme retained bound methanol after passage through Sephadex G-25. This tightly-bound methanol slowly exchanged with free [14C]-methanol from a value of 0.27 mol of [14C]methanol/mol of enzyme after 48 h incubation at 4 degrees C to a limiting value of approx. 2.5 mol of [14C]methanol/mol of enzyme after 3 weeks incubation at 4 degrees C. 5. One mol of this enzyme reduced 89.4 mol of 2,6-dichlorophenol-indophenol (via phenazine methosulphate) in the absence of any additional methanol in the assay mixture. The source of the electrons involved in this reduction is not known. | 10.1042/bj1990245 |
pubmed_828_8981 | BACKGROUND AND PURPOSE
Animal data suggest the use of beta-human chorionic gonadotropin followed by erythropoietin to promote brain repair after stroke. The current study directly translated these results by evaluating safety of this sequential growth factor therapy through a 3-center, single-dose, open-label, noncontrolled, Phase IIa trial.
METHODS
Patients with ischemic stroke 24 to 48 hours old and National Institutes of Health Stroke Scale score of 6 to 24 started a 9-day course of beta-human chorionic gonadotropin (once daily on Days 1, 3, and 5 of study participation) followed by erythropoietin (once daily on Days 7, 8, and 9 of study participation). This study also evaluated performance of serially measured domain-specific end points.
RESULTS
A total of 15 patients were enrolled. Two deaths occurred, neither related to study medications. No safety concerns were noted among clinical or laboratory measures, including screening for deep vein thrombosis and serial measures of serum hemoglobin. In several instances, domain-specific end points provided greater insight into impairments as compared with global outcome measures.
CONCLUSIONS
Results support the safety of this sequential, 2-growth factor therapy initiated 24 to 48 hours after stroke onset. | 10.1161/STROKEAHA.109.574343 |
pubmed_581_19363 | STUDY OBJECTIVES
This meta-analysis aimed to determine duration and patterns of sleep in Chinese university students.
METHODS
English (PubMed, PsycINFO, Embase) and Chinese (SinoMed, Wan Fang Database, and Chinese National Knowledge Infrastructure) databases were systematically and independently searched from their inception until August 16, 2016. Data on sleep duration and sleep patterns of tertiary student population in eligible studies were extracted and pooled using random-effects models.
RESULTS
A total of 57 studies with 82,055 university students were included in the meta-analysis. Pooled mean sleep duration was 7.08 h/d (95% confidence interval [CI]: 6.84 to 7.32 h/d). The percentage of students with sleep duration shorter than 6 h/d and 7 h/d (short sleep) was 8.4% (95% CI: 5.7% to 12.3%) and 43.9% (95% CI: 36.9% to 51.1%), respectively. In contrast, the percentage of students with sleep duration longer than 8 hours and 9 hours (long sleep) was 18.3% and 5.7%, respectively. The pooled mean bedtime was at 12:51 am. The percentage of university students who fall asleep after midnight was 23.8%. The percentage of students with sleep latency more than 30 minutes was 25.5%. The pooled mean wake-up time was at 8:04 am on weekdays and on weekends.
CONCLUSIONS
Short sleep duration and unhealthy sleep patterns were found to be common among Chinese university students. | 10.5664/jcsm.6760 |
pubmed_96_384 | 1. s-RNA nucleotidyltransferase incorporated CMP into phosphodiesterase-treated s-RNA more rapidly in the presence of Mg(2+) (10mm) than in the presence of Mn(2+) (2mm). UMP was incorporated more rapidly in the presence of Mn(2+), and at high ionic strength the incorporation of CMP was also more rapid in the presence of Mn(2+). 2. The capacity of phosphodiesterase-treated s-RNA for CMP, UMP and AMP was increased in the presence of Mn(2+). Terminal sequences of more than one UMP or AMP residue were synthesized, but these atypical reactions were inhibited when CTP was added. CMP was incorporated rapidly to form -pCpC terminal sequences and then more slowly as longer chains were formed, but very little CMP was incorporated into s-RNA-pCpCpA. 3. CMP was incorporated into phosphodiesterase-treated 5s RNA and ribosomal RNA to form short chains of polyC attached to the primer RNA. This reaction was inhibited by the presence of s-RNA. 4. A small Mn(2+)-dependent incorporation of CMP was also primed by poly(A).(U) and poly(C).(I). | 10.1042/bj1040537 |
pubmed_730_16381 | LPS and selected cytokines upregulate xanthine dehydrogenase/xanthine oxidase (XDH/XO) in cellular systems. However, the effect of these factors on in vivo XDH/XO expression, and their contribution to lung injury, are poorly understood. Rats were exposed to normoxia or hypoxia for 24 h after treatment with LPS (1 mg/kg) and IL-1beta (100 microg/kg) or sterile saline. Lungs were then harvested for measurement of XDH/XO enzymatic activity and gene expression, and pulmonary edema was assessed by measurement of the wet/dry lung weight ratio (W/D). Although treatment with LPS + IL-1beta or hypoxia independently produced a 2-fold elevation (p < 0. 05 versus exposure to normoxia and treatment with saline) in lung XDH/XO activity and mRNA, the combination of LPS + IL-1beta and hypoxia caused a 4- and 3.5-fold increase in these values, respectively. XDH/XO protein expression was increased 2-fold by hypoxia alone and 1.3-fold by treatment with LPS + IL-1beta alone or combination treatment. Compared with normoxic lungs, W/D was significantly increased by exposure to hypoxia, LPS + IL-1beta, or combination treatment. This increase was prevented by treatment of the animals with tungsten, which abrogated lung XDH/XO activity. In conclusion, LPS, IL-1beta, and hypoxia significantly upregulate lung XDH/XO expression in vivo. The present data support a role for this enzyme in the pathogenesis of acute lung injury. | 10.1164/ajrccm.158.1.9709116 |
pubmed_518_4905 | STUDY OBJECTIVE
We assess the feasibility of evaluating acute stress disorder (ASD) symptoms in the emergency department and provide an initial estimate of the prevalence, severity, and variability of these symptoms in violently injured urban children and young adults.
METHODS
The Immediate Stress Response Checklist (ISRC) was administered to violently injured patients between the ages of 8 and 24 years who presented to 2 urban, academic medical center EDs during a 10-week period. The ISRC is designed to assess ASD symptoms in children and youths immediately after a traumatic event. Responses are described using summed symptom severity scores and counts of symptoms.
RESULTS
Out of 109 identified youths, 81 participated. Fear, helplessness, or horror during the injury event was reported by 59 (73%) of study participants. Each of the following categories of ASD symptoms was reported by a significant number of youths: peritrauma dissociation, 63 (78%); posttrauma dissociation, 33 (41%); re-experiencing intrusive thoughts or images, 66 (82%); avoidance, 53 (65%); and hyperarousal, 32 (39%). The ISRC demonstrated high internal consistency (Cronbach alpha=.88) in this cohort.
CONCLUSION
The ISRC can be used to assess acute stress reactions in violently injured youths in the immediate period after injury. Although these reactions appear to be common, there is substantial variability among distinct symptom categories. These results support the need for further investigation of the relationship between immediate stress responses and longer-term emotional impact of violent injury. Clinicians should consider assessing the emotional responses of children and adolescents who are injured by interpersonal violence, even when these injuries seem minor. | 10.1067/mem.2001.118225 |
pubmed_277_13329 | We recently showed that severe hypoxia was not universally present adjacent to necrosis in human glioma xenografts and spheroids established from the M059K, M006, M006X, M006XLo and M010b cell lines. Using these glioma models, we wished to test whether oxygen serves as a regulator of cellular VEGF expression in situ. In situ hybridization (ISH) and immunohistochemistry (IHC) were used to detect vascular endothelial growth factor (VEGF) mRNA and protein expression in sections of glioma xenografts and spheroids in which hypoxic regions and regions with well-oxygenated necrosis were identified on contiguous sections by use of the hypoxia-specific marker, 3H-misonidazole. Independent validation of the presence of radiobiologically hypoxic cells in M006 xenografts was undertaken using the comet assay. Northern blotting analyses of monolayer cells demonstrated significant up-regulation of VEGF mRNA in the M006X line at oxygen concentrations of 6% and below. ISH analysis of VEGF mRNA showed unexpectedly strong staining for VEGF mRNA across the entire viable rim of M006X and M006XLo glioma spheroids. Similarly, in virtually all xenograft tumours of the M059K, M006 and M010b lines, VEGF ISH showed similar staining across all regions of healthy cells up to the border of necrosis. Only in one M006X tumour was there a suggestion of increased VEGF expression in cells adjacent to necrosis. IHC for VEGF showed good concordance with the ISH results. IHC analysis of the VEGF receptor flt-1 showed strong tumour cell staining in M006XLo glioma cells. In human glioma spheroids and xenograft tumours, regions of severe hypoxia do not correspond to areas of up-regulated VEGF expression; in fact, VEGF expression is quite uniform. Furthermore, this and our previous study demonstrate that levels of VEGF expression vary among sublines (M006, M006X and M006XLo) derived from a single human glioma specimen. | 10.1054/bjoc.1999.0975 |
pubmed_398_1912 | To identify elements of the human alpha subunit gene necessary for cell-specific expression, we generated an array of block mutations spanning approximately 400 base pairs (bp) of promoter proximal region and examined them using transient transfection analysis in pituitary (alpha T3) and placental (BeWo) cell lines. Comparison of promoter activity in the two cell types revealed both common and unique elements required for transcription in pituitary and placenta. Two strong elements, the cyclic AMP response element (CRE) and the upstream regulatory element (URE), regulate expression of the alpha subunit gene in BeWo cells. In contrast, promoter activity in alpha T3 cells requires an array of weaker elements. These include the CREs, the URE, as well as two previously described elements, pituitary glycoprotein hormone basal element (PGBE) and gonadotrope-specific element (GSE), and two new elements we designated as the alpha basal elements 1 and 2 (alpha BE1 and alpha BE2). These new elements reside between -316 and -302 bp (alpha BE1) and -296 and -285 bp (alpha BE2) of the human alpha subunit promoter and bind distinct proteins designated alpha BP1 and alpha BP2, respectively. Southwestern blot analysis revealed that alpha BE1 specifically binds 54- and 56-kDa proteins. Additional studies disclosed several potential interactions between proteins that bind the CRE and proteins that occupy PGBE, alpha BE1, and alpha BE2, suggesting that gonadotrope-specific expression occurs through a unique composite regulatory element that includes components of the placenta-specific enhancer. | 10.1074/jbc.270.44.26497 |
pubmed_578_1124 | High retropharyngeal neuroblastic tumors in children have been excised and debulked transorally or cervically, often with a covering tracheostomy. Although we and others have approached high thoracic lesions thoracoscopically, the trapdoor incision (or modification thereof) is generally reserved for cervicothoracic tumors with significant vessel encasement around the thoracic inlet. We report a case of symptomatic ganglioneuroma extending from the nasopharynx, at the level of the skull base, down to the aortic arch: macroscopic clearance was achieved via an extended trapdoor incision and without recourse to tracheostomy, transoral surgery, or transfusion. | 10.1016/j.jpedsurg.2010.06.040 |
pubmed_762_1414 | The purpose of this study was to examine the effects of nimodipine on salicylate ototoxicity in guinea pigs. The compound action potential (CAP) was recorded at the round window, and the cochlear blood flow (CBF) was measured simultaneously from the lateral wall of the basal turn of the cochlea by laser Doppler flowmetry. After administration of salicylate (100 mg/kg), the CAP thresholds were significantly elevated, by 5 to 20 dB (p < .05), and the CBF was significantly decreased (p < .05). After administration of nimodipine (2 mg/kg), the CAP thresholds were unchanged, but the CBF had increased significantly (p < .05), while systemic blood pressure had decreased significantly (p < .05). Simultaneous administration of both salicylate (100 mg/kg) and nimodipine (2 mg/kg) resulted in significant elevation of the CAP thresholds (p < .05), while the CBF did not decrease. These results suggest that nimodipine prevents the decrease in CBF induced by salicylate, but that nimodipine does not prevent the deterioration in the CAP. | 10.1177/000348940211101206 |
pubmed_643_18766 | Multi-target molecular entities, offer a path to progress both in understanding causes of disease and in defining effective small molecule treatments. Coumarin and its derivatives belong to an important group of natural compounds with diverse biological properties. They are found in vegetables and plants for which literature reports thousands of publications for the great variety of biological applications among which the photoprotective effects, thus being considered multi-targeting agents. Their furan condensed analogues constitute the family of furocoumarins, less represented in the literature, endowed with photosensitizing properties and often used for the treatment of skin diseases such as vitiligo and psoriasis. Despite the study of biological properties of linear and angular furocumarins dates back to ancient times, mainly as photosensitizers, these small molecules still represent an attractive scaffold for further development and applications in several therapeutic fields. The aim of the present review is to summarize the most promising chemical entities belonging to the class of furocumarins and coumarins, emerged in the last decades, and the methods used for their synthesis with a particular focus on main targets involved in the cystic fibrosis treatment. | 10.1016/j.ejmech.2019.07.025 |
pubmed_401_7564 | Extracellular vesicles (EVs) are considered as transporters of biomarkers for the diagnosis of cardiac diseases, playing an important role in cell-to-cell communication during physiological and pathological processes. However, specific markers for the isolation and analysis of cardiac EVs are missing, imposing limitation on understanding their function in heart tissue. For this, we performed multiple proteomic approaches to compare EVs isolated from neonate rat cardiomyocytes and cardiac fibroblasts by ultracentrifugation, as well as EVs isolated from minced cardiac tissue and plasma by EVtrap. We identified Ldb3, a cytoskeletal protein which is essential in maintaining Z-disc structural integrity, as enriched in cardiac EVs. This result was validated using different EV isolation techniques showing Ldb3 in both large and small EVs. In parallel, we showed that Ldb3 is almost exclusively detected in the neonate rat heart when compared to other tissues, and specifically in cardiomyocytes compared to cardiac fibroblasts. Furthermore, Ldb3 levels, specifically higher molecular weight isoforms, were decreased in the left ventricle of ischemic heart failure patients compared to control groups, but not in the corresponding EVs. Our results suggest that Ldb3 could be a potential cardiomyocytes derived-EV marker and could be useful to identify cardiac EVs in physiological and pathological conditions. | 10.3390/ijms23137374 |
pubmed_646_4161 | In completed and ongoing clinical trials, adenovirus-mediated (Ad.) expression of herpes-simplex-virus thymidine-kinase (HSV-tk) gene transduction followed by ganciclovir (GCV) therapy has produced limited toxicity and evidence of antitumor activity following injection of the prostate. Furthermore, this system has been shown to direct systemic antitumor activity in several experimental cancer models, including that of prostate cancer, which may serve as the basis for in-situ immunomodulatory gene therapy. In a mouse model of prostate cancer, natural killer (NK) cells have been identified as the mediator of antimetastatic activity following Ad.HSV-tk + GCV, resulting in the combination of Ad.HSV-tk and adenovirus-mediated expression of interleukin 12 (Ad.IL-12) to exploit this cytokine's ability to enhance NK proliferation and cytotoxicity. Combination therapy demonstrated superior local and systemic growth suppression over that obtained with either therapy alone. Importantly, when the metastatic tumor burden was increased to an extent that negated the growth-suppressive activity directed by Ad.HSV-tk + GCV or Ad.IL-12 alone, combination therapy continued to demonstrate significant growth suppression. Examination of tumor-infiltrating lymphocytes documented enhanced NK lytic activity following combination therapy. Therefore, it appears that the combination of Ad.HSV-tk and Ad.IL-12 should be validated in a clinical trial for the treatment of prostate cancer. | 10.1007/s003450050185 |
pubmed_655_21470 | Syndactyly type I is an autosomal dominant condition with complete or partial webbing between the third and fourth fingers or the second and third toes or both. We report here a previously undescribed phenotype of severe mesoaxial syndactyly and synostosis in patients born to affected parents. The characteristic features of these severe cases are (1) complete syndactyly and synostosis of the third and fourth fingers; (2) severe bone reduction in the proximal phalanges of the same fingers; (3) hypoplasia of the thumbs and halluces; (4) aplasia/hypoplasia of the middle phalanges of the second and fifth fingers; and (5) complete or partial soft tissue syndactyly of the toes. We report on three offspring with this phenotype from two different branches of a syndactyly type I family, suggesting that they may be homozygous for this condition. SSCP and linkage analysis indicated that neither HOXD13 nor other relevant genes in the chromosome 2q31 region was responsible for this phenotype. | 10.1136/jmg.35.10.868 |
pubmed_297_9338 | Increase in cardiac afterload as represented by hypertension is an established risk factor for cardiovascular diseases. Animal models of increased cardiac afterload offer studies aiming at identifying key molecular mechanisms and developing new therapeutic approaches. We have reported that banding of the ascending aorta in pigs results in significant cardiac hypertrophy and increased myocardial fibrosis at the chronic stages. These changes were accompanied by increased stiffness of the heart, but not by systolic dysfunction. In this chapter, we describe methods to surgically band the ascending aorta in pigs. After 3 months, animals develop systolic left ventricular pressure of >200 mmHg with above described changes in the heart. | 10.1007/978-1-4939-8597-5_26 |
pubmed_986_1520 | DNA and protein contents of pairs of sister nuclei were determined using a combined Feulgen-dinitrofluorobenzene technique. Sister nuclei were studied in binucleate cells, induced by treatment with 0.1% caffeine, and in sister mononucleate cells of untreated roots. Excised pea roots, grown in culture, were treated with 5-aminouracil to induce mitotic synchrony and with caffeine at the time of peak mitotic index, to provide the maximum number of binucleate cells. The induced binucleate cells form a marked population which was followed through a cell cycle; sister nuclei showed a correlation of volume and protein content, r = 0.79. Protein contents of sister nuclei were rarely identical and at 1 + 2 and 1 + 6 h the difference in protein contents of sister nuclei was significant (p = 0.05). Mean nuclear protein content decreased from 1 + 2 to 1 + 6 h; then, as nuclei entered S phase, their protein content increased. From 1 + 2 to 1 + 14 h the increase in protein content, in absolute amount, was identical in both sister nuclei. This suggests that there was a biphasic pattern of protein uptake; it is differential, in sister nuclei, in the first part of G1 but is identical throughout the rest of interphase. Analysis of sister nuclei from sister mononucleate cells showed a similar pattern of change; this is further evidence, from untreated cells, of a biophasic pattern of protein uptake. Caffeine-treated nuclei had lower protein contents than untreated nuclei, yet they completed a cell cycle and entered mitosis; this suggests that nonessential proteins were no longer present. It is proposed that mitosis is asymmetrical for molecules that regulate rates of macromolecular synthesis, cell growth, and progress through a cell cycle and that once the initial asymmetry has been established, it is maintained throughout interphase, even in binucleate cells in which the two nuclei share a common cytoplasm. | 10.1139/o82-044 |
pubmed_143_70 | A failure of neurodevelopmental differentiation at the level of oligodendroglial-astrocytic biprogenitors (O2A) is shown to be involved in the pathogenesis of both multiple sclerosis (MS) and glioblastoma multiforme (GBM). In this review article, we suggest that certain antigens of Hepatitis B Virus (HBV) and HBV-Vaccine (HBV-V) could act as immune stimulants in GBM treatment based on several lines of evidence. HBV-Vs may cause rare but prominent neuroimmune side effects including demyelination and multiple sclerosis, which may be associated with HBV-proteins creating antigenic mimicry of oligodendroglial progenitors. The combined prevalance of HBV and Hepatitis C Virus-carrier state is less in patients with brain tumors compared to healthy subjects. Furthermore, within the population of patients with brain tumors, the prevalence is even about two times lesser in GBM in comparison to those with a diagnosis of meningioma. Although indirectly, this epidemiological data may indicate that the immune response triggered against hepadnavirus antigens would eliminate aberrantly differentiating O2A progenitor cells giving rise to GBMs. Moreover, Hepatitis B surface antigen-antibody variable domain is among the top 100 differentially expressed transcripts in fresh frozen and formalin-fixed paraffin-embeded specimens obtained from pediatric GBM tissues in comparison to the control brain tissues. However, the provided evidence is still premature and we think that HBV-V warrants investigation first by epidemiological studies and then by animal experiments to determine whether it reduces the risk of GBM and whether it could slow GBM growth via immune stimulation. | 10.1016/j.intimp.2019.106038 |
pubmed_1089_19962 | The main purpose of this study was to investigate whether type 3 muscarinic acetylcholine receptor (M3R) dysfunction induced vascular hyperpermeability. Transwell system analysis showed that M3R inhibition by selective antagonist 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP) and small interfering RNA both increased endothelial permeability. Using coimmunoprecipitation and Western blot assay, we found that M3R inhibition increased VE-cadherin and β-catenin tyrosine phosphorylation without affecting their expression. Using PTP1B siRNA, we found that PTP1B was required for maintaining VE-cadherin and β-catenin protein dephosphorylation. In addition, 4-DAMP suppressed PTP1B activity by reducing cyclic adenosine monophosphate (cAMP), but not protein kinase Cα (PKCα). These data indicate that M3R preserves the endothelial barrier function through a mechanism potentially maintaining PTP1B activity, keeping the adherens junction proteins (AJPs) dephosphorylation. | 10.5483/bmbrep.2014.47.10.216 |
pubmed_731_3857 | In recent years, thin membrane protrusions such as cytonemes and tunneling nanotubes have emerged as a novel mechanism of intercellular communication. Protrusion-based cellular interactions allow for specific communication between participating cells and have a distinct spectrum of advantages compared to secretion- and diffusion-based intercellular communication. Identification of protrusion-based signaling in diverse systems suggests that this mechanism is a ubiquitous and prevailing means of communication employed by many cell types. Moreover, accumulating evidence indicates that protrusion-based intercellular communication is often involved in pathogenesis, including cancers and infections. Here we review our current understanding of protrusion-based intercellular communication. | 10.1146/annurev-cellbio-100617-062932 |
pubmed_598_8936 | AIMS
Remote ischemic conditionings, such as pre- and per-conditioning, are known to provide cardioprotection in animal models of ischemia. However, little is known about the neuroprotection effect of postconditioning after cerebral ischemia. In this study, we aim to evaluate the motor function rescuing effect of remote limb ischemic postconditioning (RIPostC) in a rat model of acute cerebral stroke.
METHODS
Left middle cerebral artery occlusion (MCAO) was performed to generate the rat model of ischemic stroke, followed by daily RIPostC treatment for maximum 21 days. The motor function after RIPostC was assessed with foot fault test and balance beam test. Local infarct volume was measured through MRI scanning. Neuronal status was evaluated with Nissl's, HE, and MAP2 immunostaining. Lectin immunostaining was performed to evaluate the microvessel density and area.
RESULTS
Daily RIPostC for more than 21 days promoted motor function recovery and provided long-lasting neuroprotection after MCAO. Reduced infarct volume, rescued neuronal loss, and enhanced microvessel density and size in the injured areas were observed. In addition, the RIPostC effect was associated with the up-regulation of endogenous tissue kallikrein (TK) level in circulating blood and local ischemic brain regions. A TK receptor antagonist HOE-140 partially reversed RIPostC-induced improvements, indicating the specificity of endogenous TK mediating the neuroprotection effect of RIPostC.
CONCLUSION
Our study demonstrates RIPostC treatment as an effective rehabilitation therapy to provide motor function recovery and alleviate brain impairment in a rat model of acute cerebral ischemia. We also for the first time provide evidence showing that the up-regulation of endogenous TK from remote conditioning regions underlies the observed effects of RIPostC. | 10.1111/cns.12813 |
pubmed_450_9320 | Preterm birth is the leading cause of infant morbidity and mortality. Necrotizing enterocolitis (NEC) is an inflammatory bowel disease affecting primarily premature infants, which can be lethal. Microbial intestinal colonization may alter epigenetic signatures of the immature gut establishing inflammatory and barrier properties predisposing to the development of NEC. We hypothesize that a crosstalk exists between the epigenome of the host and the initial intestinal colonizing microbiota at critical neonatal stages. By exposing immature enterocytes to probiotic and pathogenic bacteria, we showed over 200 regions of differential DNA modification, which were specific for each exposure. Reciprocally, using a mouse model of prenatal exposure to dexamethasone we demonstrated that antenatal treatment with glucocorticoids alters the epigenome of the host. We investigated the effects on the expression profiles of genes associated with inflammatory responses and intestinal barrier by qPCR-based gene expression array and verified the DNA modification changes in 5 candidate genes by quantitative methylation specific PCR (qMSP). Importantly, by 16S RNA sequencing-based phylogenetic analysis of intestinal bacteria in mice at 2 weeks of life, we showed that epigenome changes conditioned early microbiota colonization leading to differential bacterial colonization at different taxonomic levels. Our findings support a novel conceptual framework in which epigenetic changes induced by intrauterine influences affect early microbial colonization and intestinal development, which may alter disease susceptibility. | 10.1080/15592294.2016.1155011 |
pubmed_546_1837 | A month after the Health Care Financing Administration implemented its new transfer payment policy, the American Hospital Association has blasted federal investigators for unfairly targeting hospital discharge planners. According to the association, recent actions by investigators suggest that the government is set to crack down on hospitals that own home health agencies, and particularly on discharge planners, who remain under suspicion for allegedly limiting patient choice in steering patients to hospital-owned agencies. The AHA's senior associate director of policy development stresses the importance of reviewing and correcting all discharge policies to make sure financial incentives aren't driving discharge decisions. | pubmed_546_1837 |
pubmed_108_7097 | In the present study, we report a simple and efficient method of gelatin immobilization on the surface of PLA electrospun fibers using pre-treatment with a mixture of toluene and ethanol allowing to form swelled surface layer followed by gelatin adsorption from its solution in PBS. Our results demonstrate that gelatin immobilization leads to a decrease in the water contact angle from 120° to 0°, enhances scaffold strength up to 50%, and doubles the number of adhered cells and their average area. We observed that the maximum amount of gelatin (0.07 ± 0.01 mg per cm3 of the scaffold) was immobilized during the first five minutes of exposure to the gelatin solution. Modified scaffolds demonstrated increased strength. | 10.1016/j.colsurfb.2019.01.060 |
pubmed_15_22051 | AIMS
Blonanserin is a second-generation antipsychotic that was developed in Japan. We investigated the relationships between plasma concentration, the plasma anti-5-HT(2A) activity/anti-D₂ activity (S/D) ratio and extrapyramidal symptoms (EPS) in blonanserin dosing.
METHODS
The subjects were 29 outpatients with schizophrenia. We assessed EPS using the Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS). The plasma concentrations were measured by high performance liquid chromatography, and the plasma anti-D₂ and anti-5-HT(2A) activities were measured by [³H]-spiperone and [³H]-ketanserin radioreceptor assays.
RESULTS
The results revealed that there were significant correlations between both the plasma concentration and the DIEPSS total score (P<0.05). A negative correlative tendency was found between the S/D ratio and the DIEPSS total score. Furthermore, the plasma concentrations were divided into a low plasma concentration group and a high plasma concentration group, and the S/D ratios were divided into a low S/D ratio group and a high S/D ratio group. We then compared each group based on the DIEPSS total scores. The score in the high plasma concentration-low S/D ratio group was significantly higher than in the high plasma concentration-high S/D ratio, low plasma concentration-high S/D ratio and low plasma concentration-low S/D ratio groups (P<0.05 for all).
CONCLUSIONS
These findings indicate that the incidence of EPS during treatment with blonanserin is mainly determined by plasma concentration, but the incidence of EPS may be inhibited when anti-5HT(2A) activity is predominant over anti-D₂ activity. | 10.1111/j.1440-1819.2011.02311.x |
pubmed_1013_22883 | The self-organized critical (SOC) spring-block models are accessible and powerful computational tools for the study of seismic subduction. This work aims to highlight some important findings through an integrative approach of several actual seismic properties, reproduced by using the Olami, Feder, and Christensen (OFC) SOC model and some variations of it. A few interesting updates are also included. These results encompass some properties of the power laws present in the model, such as the Gutenberg-Richter (GR) law, the correlation between the parameters a and b of the linear frequency-magnitude relationship, the stepped plots for cumulative seismicity, and the distribution of the recurrence times of large earthquakes. The spring-block model has been related to other relevant properties of seismic phenomena, such as the fractal distribution of fault sizes, and can be combined with the work of Aki, who established an interesting relationship between the fractal dimension and the b-value of the Gutenberg-Richter relationship. Also included is the work incorporating the idea of asperities, which allowed us to incorporate several inhomogeneous models in the spring-block automaton. Finally, the incorporation of a Ruff-Kanamori-type diagram for synthetic seismicity, which is in reasonable accordance with the original Ruff and Kanamori diagram for real seismicity, is discussed. | 10.3390/e24040435 |
pubmed_539_5303 | Atopic dermatitis (eczema) is the commonest of the childhood dermatoses, accounting for 20% of all dermatological referrals with many cases continuing into adulthood. The morbidity and costs to society are high. | 10.12968/hosp.2001.62.3.1531 |
pubmed_239_11839 | Recent literature has revealed underestimation effects in numerical judgments when adult participants are presented with emotional stimuli (as opposed to neutral). Whether these numerical biases emerge early in development however, or instead reflect overt, learned responses to emotional stimuli across development are unclear. Moreover, reported links between numerical acuity and mathematics achievement point to the importance of exploring how numerical approximation abilities in childhood may be influenced in real-world affective contexts. In this study, children (aged 6-10 years) and adults were presented with happy and neutral facial stimuli in the context of a numerical bisection task. Results reveal that children, like adults, underestimate number following emotional (i.e., happy) faces (relative to neutral). However, children's, but not adult's, responses were also significantly more precise following emotional stimuli. In a second experiment, adult judgments revealed a similar increase in precision following emotional stimuli when numerical discriminations were more challenging (involving larger sets). Together, results are the first to reveal children, like adults, underestimate number in the context of emotional stimuli and this underestimation bias is accompanied with enhanced response precision. | 10.1080/17470218.2017.1318154 |
pubmed_697_16345 | Robert Bartlett, emeritus Professor of surgery at the University of Michigan in Ann Arbor, USA, transformed classical works of world literature (Charles Dickens: A Christmas Carol, Lewis Carroll: Alice in Wonderland) into teaching aids for advanced training in intensive care medicine. He recently turned his hand to the well-known work of Ernest Hemingway: the Nobel Prize winning novel The Old Man and the Sea. Subsequent to Robert Bartlett's essay this article provides background information and comments on the current problems in modern intensive care medicine addressed in his essay. | 10.1007/s00101-016-0239-3 |
pubmed_1113_661 | OBJECTIVE
Meningioma-associated protein (MAC30) is overexpressed in several types of cancers, but its therapeutic implication in the patients has not been studied. We examined the relationship of MAC30 with clinicopathological and biological factors in rectal cancer patients with or without radiotherapy (RT).
METHODS
MAC30 was immunohistochemically examined in 75 distant and 91 adjacent normal mucosa specimens, 132 primary tumours and 39 lymph node metastases from rectal cancer patients participating in a clinical trial of preoperative RT.
RESULTS
In the RT group, MAC30 was or tended to be positively correlated with infiltrated growth pattern (p = 0.02), PRL (phosphatase of regenerating liver, p = 0.01) and Ki-67 expression (p = 0.06). MAC30 at the invasive margin of the metastasis was related to poor survival (p = 0.02) in the whole group of patients. MAC30 in primary tumours was not related to recurrence and survival in the non-RT or RT group.
CONCLUSIONS
MAC30 expression in metastasis was an indicator for poor survival. After RT, MAC30 seemed to be more related to aggressive morphological and biological factors; however, we did not find direct evidence that MAC30 expression was related to the outcome of patients with or without RT. | 10.1159/000106449 |
pubmed_689_24227 | Recent developments in massive machine-type communication (mMTC) scenarios have given rise to never-seen requirements, which triggered the Industry 4.0 revolution. The new scenarios bring even more pressure to comply with the reliability and communication security and enable flawless functionality of the critical infrastructure, e.g., smart grid infrastructure. We discuss typical network grid architecture, communication strategies, and methods for building scalable and high-speed data processing and storage platform. This paper focuses on the data transmissions using the sets of standards IEC 60870-6 (ICCP/TASE.2). The main goal is to introduce the TASE.2 traffic generator and the data collection back-end with the implemented load balancing functionality to understand the limits of current protocols used in the smart grids. To this end, the assessment framework enabling generating and collecting TASE.2 communication with long-term data storage providing high availability and load balancing capabilities was developed. The designed proof-of-concept supports complete cryptographic security and allows users to perform the complex testing and verification of the TASE.2 network nodes configuration. Implemented components were tested in a cloud-based Microsoft Azure environment in four geographically separated locations. The findings from the testing indicate the high performance and scalability of the proposed platform, allowing the proposed generator to be also used for high-speed load testing purposes. The load-balancing performance shows the CPU usage of the load-balancer below 15% while processing 5000 messages per second. This makes it possible to achieve up to a 7-fold improvement of performance resulting in processing up to 35,000 messages per second. | 10.3390/s21206793 |
pubmed_410_10925 | Diabetic osteoporosis (DOP) is the leading complication continuously threatening the bone health of patients with diabetes. A key pathogenic factor in DOP is loss of osteocyte viability. However, the mechanism of osteocyte death remains unclear. Here, we identified ferroptosis, which is iron-dependent programmed cell death, as a critical mechanism of osteocyte death in murine models of DOP. The diabetic microenvironment significantly enhanced osteocyte ferroptosis in vitro, as shown by the substantial lipid peroxidation, iron overload, and aberrant activation of the ferroptosis pathway. RNA sequencing showed that heme oxygenase-1 (HO-1) expression was notably upregulated in ferroptotic osteocytes. Further findings revealed that HO-1 was essential for osteocyte ferroptosis in DOP and that its promoter activity was controlled by the interaction between the upstream NRF2 and c-JUN transcription factors. Targeting ferroptosis or HO-1 efficiently rescued osteocyte death in DOP by disrupting the vicious cycle between lipid peroxidation and HO-1 activation, eventually ameliorating trabecular deterioration. Our study provides insight into DOP pathogenesis, and our results provide a mechanism-based strategy for clinical DOP treatment. | 10.1038/s41413-022-00198-w |
pubmed_840_20624 | In mammals, coat complex II (COPII)-coated transport vesicles deliver secretory cargo to vesicular tubular clusters (VTCs) that facilitate cargo sorting and transport to the Golgi. We documented in vitro tethering and SNARE-dependent homotypic fusion of endoplasmic reticulum-derived COPII transport vesicles to form larger cargo containers characteristic of VTCs ( Xu, D., and Hay, J. C. (2004) J. Cell Biol. 167, 997-1003). COPII vesicles thus appear to contain all necessary components for homotypic tethering and fusion, providing a pathway for de novo VTC biogenesis. Here we demonstrate that antibodies against the endoplasmic reticulum/Golgi SNARE Syntaxin 5 inhibit COPII vesicle homotypic tethering as well as fusion, implying an unanticipated role for SNAREs upstream of fusion. Inhibition of SNARE complex access and/or disassembly with dominant-negative alpha-soluble NSF attachment protein (SNAP) also inhibited tethering, implicating SNARE status as a critical determinant in COPII vesicle tethering. The tethering-defective vesicles generated in the presence of dominant-negative alpha-SNAP specifically lacked the Rab1 effectors p115 and GM130 but not other peripheral membrane proteins. Furthermore, Rab effectors, including p115, were shown to be required for homotypic COPII vesicle tethering. Thus, our results demonstrate a requirement for SNARE-dependent tether recruitment and function in COPII vesicle fusion. We anticipate that recruitment of tether molecules by an upstream SNARE signal ensures that tethering events are initiated only at focal sites containing appropriately poised fusion machinery. | 10.1074/jbc.M606044200 |
pubmed_78_16978 | PURPOSE
To evaluate the efficacy and tolerance of the irinotecan plus docetaxel combination in patients with advanced non-small cell lung cancer (NSCLC).
PATIENTS AND METHODS
Thirty-nine chemotherapy-naïve patients with advanced NSCLC were treated with irinotecan 200mg/m2 followed by docetaxel 80 mg/m2 intravenously on day 1 with granulocyte colony-stimulating factor (150 microg/m2) support from day 2 to 9. Treatment was repeated every 3 weeks.
RESULTS
A partial response was achieved in 9 (23%; 95% confidence interval 9.85-36.3%) patients; stable and progressive disease were observed in 10 (25.6%) and 20 (51.4%) patients, respectively. The median duration of response was 7.1 months and the median time to tumor progression 3 months. The median survival time was 10.8 months and the 1-year survival 42.2%. Four (10.3%) patients developed grade 4 neutropenia and all but one were complicated with fever; there was no treatment-related death. Nine (23.1%) patients developed grade 3 or 4 diarrhea while grade 2 or 3 fatigue occurred in nine (23.1%), and grade 3 mucositis in two (2.6%).
CONCLUSION
The combination of irinotecan/docetaxel is a relatively active non-platinum-based chemotherapy regimen with manageable toxicity, which could be given in an outpatient basis; this regimen merits to be further studied in order to improve its tolerance and evaluate its clinical relevance in patients who can not tolerate platinum-based doublets. | 10.1016/j.lungcan.2005.05.004 |
pubmed_33_19173 | One major concern regarding soft tissue allograft use in surgical procedures is the risk of disease transmission. Current techniques of tissue sterilization, such as irradiation have been shown to adversely affect the mechanical properties of soft tissues. Grafts processed using Biocleanse processing (a proprietary technique developed by Regeneration Technologies to sterilize human tissues) will have better biomechanical characteristics than tissues that have been irradiated. Fifteen pairs of cadaveric Achilles tendon allografts were obtained and separated into three groups of 10 each. Three treatment groups were: Biocleanse, Irradiated, and Control (untreated). Each specimen was tested to determine the biomechanical properties of the tissue. Specimens were cyclically preloaded and then loaded to failure in tension. During testing, load, displacement, and optical strain data were captured. Following testing, the cross sectional area of the tendons was determined. Tendons in the control group were found to have a higher extrinsic stiffness (slope of the load-deformation curve, p = .005), have a higher ultimate stress (force/cross sectional area, p = .006) and higher ultimate failure load (p = .003) than irradiated grafts. Biocleanse grafts were also found to be stiffer than irradiated grafts (p = .014) yet were not found to be statistically different from either irradiated or non-irradiated grafts in terms of load to failure. Biocleanse processing seems to be a viable alternative to irradiation for Achilles tendon allografts sterilization in terms of their biomechanical properties. | 10.1007/s10561-012-9340-2 |
pubmed_827_9514 | BACKGROUND
Planned inguinal herniorrhaphy may present a clinical dilemma when no hernia is found. No large-scale data are available on the incidence of this problem, and, therefore, no recommendations exist for choice of surgical intervention.
MATERIAL AND METHODS
Data were extracted from the Danish Hernia Database covering the interval from 1 January 1998-5 April 2002, and included 42,356 groin hernia repairs. Results. No hernia was found in 313 cases (0.74%). These patients were divided into three groups (lipomas, no pathology, and a "weak abdominal wall") and analysed according to surgical technique. There were 11 reoperations (3.5%) of which three were femoral and eight inguinal hernias, without differences between type of initial operation (herniorrhaphy or no herniorrhaphy).
CONCLUSION
This study of 42,356 groin hernia repairs showed that in 313 patients (0.74%), no hernia was found. Recurrences did not occur with higher frequency in patients receiving no repair. Based on these data and the risk of chronic postherniorrhaphy pain, we suggest that no repair be performed when no inguinal hernia is found during planned inguinal herniorrhaphy. | 10.1007/s10029-004-0211-z |
pubmed_1010_21557 | Objective: To evaluate the prognostic impact of neuromuscular blocking agents (NMBA) on patients with acute respiratory distress syndrome (ARDS). Method: Online search of MEDLINE, Embase, Web of Science, CNKI, CBM and other Chinese databases for randomized controlled trials (RCTs) of NMBA in patients with ARDS from January 1994 to June 2019 was done, and literature was selected according to inclusion and exclusion criteria. The patients were divided into NMBA group and non-NMBA group according to whether NMBA was adopted or not. The prognostic indicators (ICU mortality, 28 d mortality, 90 d mortality) and NMBA-related complications (ICU acquired muscle weakness, barometric injury, pneumothorax) of the patients in the two groups were mainly analyzed. Meta-analysis of the data was performed using RevMan 5.0 software. Results: A total of 6 RCTs were included, and 1 502 patients were enrolled, including 761 in the NMBA group and 741 in the no-NMBA group. The 90-day mortality in the NMBA group and no-NMBA group were 38.8% and 42.6%, OR=0.87 (95%CI: 0.70-1.07, P=0.190); the 28-day mortality rates were 32.5% and 36.5%, OR=0.71 (95%CI: 0.45-1.11, P=0.130); ICU mortality rates were 31.8% and 43.8%, OR=0.60 (95%CI: 0.41-0.88, P=0.009). Conclusion: NMBA can reduce the ICU mortality of moderate to severe ARDS patients, but not reduce 28-day and 90-day mortality. | 10.3760/cma.j.issn.0376-2491.2019.48.012 |
pubmed_46_13929 | Stability of faecal egg excretion and correlation with results related to worm burden at the initial phase of schistosomiasis mansoni were observed in two groups of mice infected with different Schistosoma mansoni cercarial burdens, by means of analysis of quantitative parasitological studies and schistosome counts after perfusion. Thus, it may be stated that few quantitative parasitological stool examinations could be sufficient to express the infection intensity at the initial phase, on the same grounds that it was already demonstrated at the chronic phase. Furthermore, it is confirmed that the use of the number of eggs passed in the faeces as a tool to estimate the worm burden at the initial phase of schistosome infection is adequate. | 10.1590/s0036-46651995000400007 |
pubmed_294_19732 | BACKGROUND
Survival times and overall response rates are generally poor in patients with unresectable hepatocellular carcinoma submitted to systemic chemotherapy. Limited data are reported in the literature concerning the factors influencing survival among this subset of patients but the distribution of these variables may affect the results of clinical trials.
PATIENTS AND METHODS
The data on 103 patients undergoing systemic chemotherapy at the Istituto Nazionale Tumori from January 1988 through July 1991 have been analyzed using univariate and Cox multivariate analysis. Forty-eight patients were treated with mitoxantrone alone, 40 with mitoxantrone plus beta-interferon, 11 with fluorouracil plus folinic acid and the remaining four with adriamycin.
RESULTS
Median survival time, and 6-month and 12-month survival rates, were 7.1, 55% and 29%, respectively. Lactate dehydrogenase value (P = 0.0009), TNM stage (P = 0.001), vascular invasion (P = 0.001), bilirubin (P = 0.008), Child status (P = 0.01), aspartate amino-transferase (P = 0.02), extent of liver involvement (P = 0.02) and performance status (P = 0.03) were the most significant factors influencing survival in univariate analysis. In the multivariate analysis, aspartate amino-transferase (P = 0.02) and, particularly, TNM stage (p = 0.0009) were confirmed as independent variables correlating with survival. A prognostic index was calculated on the basis of these factors and high- and low-risk groups were identified. Median survival time and 12-month survival were 11.1 months and 43% for the low-risk group, and 4.0 months and 9% for the high-risk group (p = 0.0005).
CONCLUSION
The results of this analysis may provide guidance for the design of future therapeutic trials in unresectable hepatocellular carcinoma. In particular, patient stratification should be considered for further clinical trials. | 10.1093/oxfordjournals.annonc.a058560 |
pubmed_1007_10873 | Two response measures for reporting visually perceived egocentric distances-verbal judgments and blind manual reaches-were compared using a within-trial methodology. The expected range of possible target distances was manipulated by instructing the subjects that the targets would be between .50 and 1.00 of their maximum arm reach in one session and between .25 and .90 in another session. The actual range of target distances was always .50-.90. Verbal responses varied as a function of the range of expected distances, whereas simultaneous reaches remained unaffected. These results suggest that verbal responses are subject to a cognitive influence that does not affect actions. It is suggested that action responses are indicative of absolute perception, whereas cognitive responses may reflect only relative perception. The results also indicate that the dependant variable utilized for the study of depth perception will influence the obtained results. | 10.3758/pbr.15.2.437 |
pubmed_386_16608 | Hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS) are transmitted to humans through infection with the old- and new-world hantaviruses, respectively. Together these diseases affect tens of thousands of people every year, and no specific treatment is available. To investigate whether ribavirin treatment for hantaviruses infections decreases disease severity, we conducted a meta-analysis involving human and animal studies. After defining the research protocol and criteria for inclusion/exclusion, we identified seven studies. We found that in groups with HPS who were treated with ribavirin, there was no significant reduction in mortality (RR 0.99, 95 % CI 0.60-1.61, I(2) = 0 %). On the other hand, for animal group with HPS-like disease, there was significant increase in survival (RR 0.05, 95 % CI 0.01-0.34, I(2) = 0 %). For animal group infected with the old-world hantaviruses, treated with ribavirin, there was a statistically significant increase in survival (RR 0.56, 95 % CI 0.42-0.76, I(2) = 64 %). Similarly, for humans with HFRS treated, there was increase in survival (RR 0.28, 95 % CI 0.08-1), although only a study exist. Our meta-analysis provides data that should be interpreted with caution, partly due to the limited number of studies available. Additionally, the results of the application of ribavirin in the population with HPS could not be determined, particularly in patients in the end stage of this disease. | 10.1007/s13337-014-0219-7 |
pubmed_434_828 | D-serine is a co-agonist of NMDA receptor (NMDAR) and plays important roles in synaptic plasticity mechanisms. Serine racemase (SR) is a brain-enriched enzyme that converts L-serine to D-serine. SR interacts with the protein interacting with C-kinase 1 (PICK1), which is known to direct protein kinase C (PKC) to its targets in cells. Here, we investigated whether PKC activity regulates SR activity and D-serine availability in the brain. In vitro, PKC phosphorylated SR and decreased its activity. PKC activation increased SR phosphorylation in serine residues and reduced D-serine levels in astrocyte and neuronal cultures. Conversely, PKC inhibition decreased basal SR phosphorylation and increased cellular D-serine levels. In vivo modulation of PKC activity regulated both SR phosphorylation and D-serine levels in rat frontal cortex. Finally, rats that completed an object recognition task showed decreased SR phosphorylation and increased D-serine/total serine ratios, which was markedly correlated with decreased PKC activity in both cortex and hippocampus. Results indicate that PKC phosphorylates SR in serine residues and regulates D-serine availability in the brain. This interaction may be relevant for the regulation of physiological and pathological mechanisms linked to NMDAR function. | 10.1111/j.1471-4159.2010.07102.x |
pubmed_515_20481 | In order to review the current status of the potential relationship between anesthesia and Alzheimer's disease, a group of scientists recently met in Philadelphia for a full day of presentations and discussions. This special article represents a consensus view on the possible link between Alzheimer's disease and anesthesia and the steps required to test this more definitively. | 10.1213/ane.0b013e318199dc72 |
pubmed_474_6583 | The development of flukes that resulted from a challenge dose of 175 F. hepatica metacercariae was compared in 4 groups of sheep that were maintained under grazing conditions on fluke-free pasture. One group had been previously uninfected and all subgroups of each of the other 3 groups had been exposed to one of a range of previous doses of metacercariae. The preliminary infections of 2 of the 3 groups had been terminated respectively after 7 and 14 weeks. The third previously infected group had received its preliminary infection as 2 doses of metacercariae, 7 weeks apart. The latter infection had been terminated after 14 weeks. No appreciable differences in the mean numbers, length, prepatent period or fecundity of flukes, established as a result of the challenge dose of metacercariae, were detected between the control group and the 3 previously infected groups. It was concluded that under the conditions of the present experiment no evidence was detected that would suggest that previous infection with F. hepatica conferred any significant resistance to a future challenge. | 10.1111/j.1751-0813.1979.tb15163.x |
pubmed_210_7918 | Inhalation of airborne antibiotic resistance genes (ARGs) can lead to antimicrobial resistance and potential health risk. In modern society, increasing individuals stay more indoors, however, studies regarding the exposure to airborne ARGs in indoor environments and the associated risks remain limited. Here, we compared the variance of aerosol-associated ARGs, bacterial microbiomes, and their daily intake (DI) burden in dormitory, office, and outdoor environments in a university in Tianjin. The results indicated that compared to outdoor aerosols, indoors exhibited significantly higher absolute abundance of both ARG subtypes and mobile genetic elements (MGEs) (1-7 orders of magnitude), 16S rRNA genes (2-3 orders), and total culturable bacteria (1-3 orders). Furthermore, we observed that significantly different airborne bacterial communities are the major drivers contributing to the variance of aerosol-associated ARGs in indoor and outdoor aerosols. Notably, the high abundances of total bacteria, potential pathogenic genera, and ARGs (particularly those harbored by pathogens) in indoor and outdoor aerosols, especially in indoors, may pose an increased exposure risk via inhalation. The successful isolation of human pathogens such as Elizabethkingia anopheles, Klebsiella pneumonia, and Delftia lacustris resistant to the "last-resort" antibiotics carbapenems and polymyxin B from indoor aerosols further indicated an increased exposure risk in indoors. Together, this study highlights the potential risks associated with ARGs and their inhalation to human health in indoor environments. | 10.1016/j.envpol.2020.115620 |
pubmed_921_18104 | "Soluble liver antigen" (SLA) has been reported to be an infrequent but in certain cases a unique marker of autoimmune hepatitis, with cytokeratins 8 and 18 as major antigenic components. Using precharacterized sera, we could confirm trypsin sensitivity and a molecular weight of approximately 50 kD of the reactive protein. However, the reaction differed from that of cytokeratins 8 and 18 by molecular weight and a pI of 7.5. A significant reactivity to cytokeratin 8 and 18 preparations was seen in only 1/12 patients. Immunoscreening of a human liver expression gene bank yielded no clones with sequence homology to cytokeratins. We conclude that reactivity in SLA positive sera is not mainly directed against cytokeratins 8/18 and recommend native antigen preparations for diagnostic use until the exact molecular nature of the 52 kD SLA antigen has been elucidated. | pubmed_921_18104 |
pubmed_330_14223 | We previously proposed an integrated electroencephalography (EEG), magnetoencephalography (MEG), and functional Magnetic Resonance Imaging (fMRI) model based on an extended neural mass model (ENMM) within a single cortical area. In the ENMM, a cortical area contains several minicolumns where strengths of their connections diminish exponentially with their distances. The ENMM was derived based on the physiological principles of the cortical minicolumns and their connections within a single cortical area to generate EEG, MEG, and fMRI signals. The purpose of this paper is to further extend the ENMM model from a single-area to a multi-area model to develop a neural mass model of the entire brain that generates EEG and MEG signals. For multi-area modeling, two connection types are considered: short-range connections (SRCs) and long-range connections (LRCs). The intra-area SRCs among the minicolumns within the areas were previously modeled in the ENMM. To define inter-area LRCs among the cortical areas, we consider that the cell populations of all minicolumns in the destination area are affected by the excitatory afferent of the pyramidal cells of all minicolumns in the source area. The state-space representation of the multi-area model is derived considering the intra-minicolumn, SRCs', and LRCs' parameters. Using simulations, we evaluate effects of parameters of the model on its dynamics and, based on stability analysis, find valid ranges for parameters of the model. In addition, we evaluate reducing redundancy of the model parameters using simulation results and conclude that the parameters of the model can be limited to the LRCs and SRCs while the intra-minicolumn parameters stay at their physiological mean values. The proposed multi-area integrated E/MEG model provides an efficient neuroimaging technique for effective connectivity analysis in healthy subjects as well as neurological and psychiatric patients. | 10.1016/j.neuroimage.2010.01.034 |
pubmed_365_10050 | Recent guidelines for the management of asthma have emphasized the role of inflammation in persistent asthma. Medications with anti-inflammatory properties are recommended as the primary long-term-control medications. Of the available choices of long-term-control medications, inhaled corticosteroids are the preferred medication. A literature review of the available studies supports this recommendation of inhaled corticosteroids as the preferred agents for long-term control. Other long-term-control medications--specifically nedocromil, theophylline, and leukotriene modifiers, but not cromolyn--can supplement the beneficial effect of inhaled corticosteroids on pulmonary function and symptom control. Long-acting beta2-adrenergic agonists can also provide an additive clinical benefit to inhaled corticosteroids on symptom control and pulmonary function, but they do not provide additional anti-inflammatory effect. Extended long-term studies of each of the long-term-control medications with anti-inflammatory actions are needed to assess their specific effect on airway remodeling and on the natural history of asthma. | 10.1016/s0091-6749(98)70003-x |
pubmed_82_8366 | Although managed care seems to serve well the interests of non-elderly enrollees and their payers, elderly people face more risks. Chronic conditions, multiple problems, and more limited resources make them more vulnerable, whereas multiple payer sources make them more complicated to cover. This synthesis of managed care delivered in Medicare and Medicaid demonstration projects serving elderly beneficiaries shows that managed care plans either select or attract enrollees who suffer fewer frailties than those served in fee-for-service settings, exhibit reluctance to enter rural markets, provide a broad range of elderly-specific services, offer more comprehensive coverage and services, and result in greater perceived access problems, particularly for vulnerable subgroups. Plans operate more cheaply by using fewer resources, even after adjusting for case mix differences. Managed care enrollees tend to be more satisfied with financial and coverage aspects, whereas fee-for-service enrollees report higher satisfaction on other dimensions. In acute care settings, process of care findings were mixed, whereas clinical and self-reported outcome indicators were no better and in some instances worse in managed care. Long-term care enrollees, in the few studies reported, consistently faired worse in both the processes and outcomes of care. These findings suggest that further research on the effects of managed care in its rapidly changing incarnations is needed, particularly with respect to how to improve the quality of acute and long-term care delivered to elderly people and the proper role of government and other key actors in the health care system. | 10.1177/106286069801300304 |
pubmed_406_11481 | The patient selection criteria for most modalities of psychotherapy have not yet been clearly articulated. This paper presents a decision-tree model outlining the factors that incline a clinician to perform a family evaluation, then to decide upon family treatment instead of another form of therapy, and finally to settle upon the particular duration and intensity of family treatment. We have compiled screening criteria, based on research and clinical opinion, to be applied in the utilization review of the decisions made at each of these steps. This method can be used to evaluate the appropriateness of care and render decision-making explicit and accountable; it may also have considerable value in training and research. | 10.1111/j.1545-5300.1979.00391.x |
pubmed_1082_15852 | The effects of fluvastatin sodium (XU62-320), a new type of inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, on plasma cholesterol and triacylglycerol levels were investigated using homozygous Watanabe-heritable hyperlipidemic (WHHL) rabbit, an LDL-receptor-deficient animal which expresses a hepatic LDL receptor activity less than 5% that of control rabbits. Plasma levels of total, VLDL- and LDL-cholesterol were decreased profoundly after oral administration of fluvastatin at a dose of 50 mg/kg per day for 4 weeks. Plasma triacylglycerol levels were not affected by fluvastatin. Hepatic HMG-CoA reductase activity increased by 3-fold and hepatic LDL receptor activity increased by only 3.7-fold, as calculated by Scatchard plot analysis, with fluvastatin administration for 4 weeks, and the hepatic mRNA level for the rabbit LDL receptor was increased by 3-fold. Combined administration of fluvastatin (50 mg/kg per day) and cholestyramine, a bile acid sequestrant resin, at a level of 2% of the diet for 4 weeks more profoundly decreased plasma total, VLDL- and LDL-cholesterol levels with induction of hepatic cholesterol 7 alpha-hydroxylase and no further induction of the hepatic LDL receptor. Plasma triacylglycerol levels were increased by the combination treatment. These results suggest that high dose of fluvastatin sodium is effective in lowering plasma cholesterol levels in homozygous WHHL rabbits through the shared mechanisms involving decrease in production and secretion of cholesterol from the liver and the induction of hepatic LDL receptor. Additional effect of cholestyramine on decrease in plasma cholesterol levels seems to be due to the further decrease in hepatic cholesterol secretion by up-regulation of hepatic cholesterol 7 alpha-hydroxylase. | 10.1016/0005-2760(95)00155-6 |
pubmed_909_32 | BACKGROUND
In a Dutch guideline on physiotherapy (PT) in hip and knee osteoarthritis, a number of recommendations on post-acute (i.e. after discharge from hospital) PT following total hip (THA) and total knee (TKA) arthroplasty were included. Little is known about the uptake of these recommendations in daily clinical practice.
OBJECTIVE
The aim of the present study was to determine the extent to which the guideline recommendations regarding post-acute PT after THA and TKA are followed in daily clinical practice.
METHODS
An online pilot survey on the delivery of post-acute, postoperative PT was sent to a random sample of 957 Dutch physiotherapists. The survey included questions on the application of recommended, neither recommended nor advised against, and advised against treatment modalities and various treatment modalities for which there were no formulated recommendations.
RESULTS
A total of 219 physiotherapists completed the questionnaire, with a mean age of 40 years (standard deviation 12.6), 55% female and 95% working in primary care. The vast majority reported the use of the recommended exercise modalities (muscle strengthening exercises (96%), and functional exercises (99%). Continuous passive motion, which was neither recommended nor advised against, and electrical muscle stimulation, which was not recommended, were provided by 1%. Reported treatment modalities for which there were no formulated recommendations included patient education (99%), gait training (95%), active range of motion (ROM) exercises (93%), balance exercises (86%), passive ROM exercises (58%), aerobic exercises (50%), massage (18%) and cold therapy (11%).
CONCLUSIONS
The vast majority of physiotherapists reported adhering to recommendations on post-acute postoperative PT in THA and TKA patients after discharge from hospital. Although yet to be confirmed in a larger nationwide survey, the relatively high frequency of use of many other treatment modalities, for which there were no formulated recommendations, suggests the need to extend the current set of recommendations to include evidence-based statements on additional treatment modalities. | 10.1002/msc.1067 |
pubmed_121_15877 | Intestinal organoids are physiologically relevant tools used for cellular models. However, the suitability of organoids to examine biological functions over existing established cell lines lacks sufficient evidence. Cytochrome P450 3A4 (CYP3A4) induction by pregnane X receptor ligands, glucose uptake via sodium/glucose cotransporter 1, and microsomal triglyceride transfer protein-dependent ApoB-48 secretion, which are critical for human intestinal metabolism, were observed in organoid-derived two-dimensional cells but little in Caco-2 cells. CYP3A4 induction evaluation involved a simplified method of establishing organoids that constitutively expressed a reporter gene. Compound screening identified several anticancer drugs with selective activities toward Caco-2 cells, highlighting their characteristics as cancer cells. Another compound screening revealed a decline in N-(4-hydroxyphenyl)retinamide cytotoxicity upon rifampicin treatment in organoid-derived cells, under CYP3A4-induced conditions. This study shows that organoid-derived intestinal epithelial cells (IECs) possess similar physiological properties as intestinal epithelium and can serve as tools for enhancing the prediction of biological activity in humans. | 10.1016/j.isci.2022.104542 |
pubmed_569_2960 | OBJECTIVE
Fresh osteochondral allograft transplantation (OCA) is an increasingly available option for patients with damage to the bone-cartilage complex of the distal femur. This study prospectively assesses osseous integration and early clinical results following fresh OCA with single or multiple cylindrical grafts to the femoral condyle.
DESIGN
Patients with grade 4 International Cartilage Repair Society (ICRS) defects of the distal femur were treated with OCA. Outcome measures were collected preoperatively and postoperatively at 6, 12, and 24 months. Computed tomography (CT) scans obtained at 6 months were used to assess degree of osseous incorporation regionally.
RESULTS
Thirty-four patients, with a mean age of 34.5 years (range, 15-61), with a mean femoral osteochondral lesion of 5.7 cm(2) (range, 1.5-15.0) due to focal osteoarthritis, osteochondritis dissecans, and avascular necrosis, are reported. Statistically significant (P < 0.05) mean improvement in outcome scores at 2 years included Knee Injury and Osteoarthritis Outcomes Score (KOOS) pain, sports and recreation, quality of life, and International Knee Documentation Committee (IKDC). CT imaging indicated grafts implanted to direct weightbearing regions had >75% incorporation (20/26 grafts) compared to <50% incorporation in the indirect weightbearing regions (8/14 grafts). A greater degree of incorporation and earlier outcome improvement were found after single (n = 23) compared to multiple (n = 11) grafts.
CONCLUSION
CT scans were used to assess osseous incorporation of fresh osteochondral allografts in a cohort that showed significant improvements after 2 years. Single-graft implantation is associated with stable incorporation of a greater percentage of the graft. Lesser incorporation appears more frequently with grafts in posterior indirect weightbearing regions of the condyle and multiple contiguous grafts. | 10.1177/1947603511410418 |
pubmed_880_5032 | ZF87/Pur1 is a zinc finger protein that binds to the purine-rich element ME1a1 within the c-myc P2 promoter. To better understand the effect of ZF87/Pur1 on c-myc gene expression, the gene was stably expressed in nontransformed NIH3T3 fibroblasts or was transiently overexpressed in transformed COS cells. The protein was targeted almost exclusively to the nucleus. In nuclear extracts from both cell types, the ectopically expressed ZF87/Pur1 protein generated a novel band in the gel-shift assay, due possibly to a modification since it was found that the protein was phosphorylated on serine and threonine in vivo. When the NIH3T3 cell lines constitutively expressing ZF87/Pur1 were analyzed under a variety of growth conditions, it was found that c-myc expression was not affected. In addition; overexpression of ZF87/Pur1 in COS cells did not affect transcription from the c-myc promoter in a cotransfection assay, but did increase the level of transcription from a promoter containing multiple ME1a1 binding sites. The data indicate that overexpression of ZF87/Pur1 alone is not enough to affect transcription from the c-myc P2 promoter; transcriptional activation from P2 may require additional limiting factors such as E2F. | 10.3892/ijo.5.5.1085 |
pubmed_383_1167 | BACKGROUND
Health outcomes of Indigenous patients are impacted by culturally unsafe specialty care environments. The 'Educating for Equity (E4E)' program is a continuing professional development (CPD) intervention which incorporates skill-based teaching to improve Indigenous patient experiences and outcomes in healthcare interactions.
METHODS
The E4E program was delivered to rheumatologists in two phases, each delivered as experiential learning workshops where participants engaged with and applied course content within an interactive format focusing on real-time feedback. The phase 1 workshop focused on skill development of E4E Framework concepts and principles. Phase 2 concentrated on building capacity for teaching of E4E content. Evaluation of the program's effectiveness was through longitudinal responses to the Social Cultural Confidence in Care Survey (SCCCS), self-reported strategies employed to address social issues and improve therapeutic relationships, engagement with teaching others, and satisfaction with the program.
RESULTS
Two cohorts of participants have participated in the program (n = 24 Phase 1, n = 10 Phase 2). For participants completing both phases of training, statistically significant improvements were observed in exploring social factors with patients, gaining knowledge and skills related to cultural aspects of care, improved communication and relationship building, and reflections on held stereotypes. Strategies to address social issues and build therapeutic relationships remained consistent throughout participation, while the training enhanced exploration and confidence to ask about cultural and traditional practices, and stronger communication strategies for exploring beliefs, expectations, social barriers, and residential school impacts on health. Participants reported feeling prepared to teach Indigenous health concepts to others and subsequently lead teaching with residents, fellows, and allied health professionals. Satisfaction with the delivery and content of the workshops was high, and participants valued interactions with peers in learning.
CONCLUSIONS
This CPD intervention had a beneficial impact on self-reported confidence and enhanced practice strategies to engage with Indigenous patients. | 10.1186/s12909-021-02551-9 |
pubmed_367_24439 | Besides natural disasters and naturally occurring novel infectious diseases, nothing potentially threatens the health and stability of nations and health systems as much as the devastating threat and unfathomability of bioterrorism. Other than attempts at political solutions and interdictive attempts, only antimicrobials and vaccines offer possible means for protection. Of these, vaccines offer the most immediate and definitive of preventive solutions. Limiting the development and use of vaccines however are social, political, ethical, and economic considerations, and this article will provide a brief exploration of each of these issues and the intersection with the need for such vaccines. In this article we define bioterrorism as the deliberate use of naturally occurring or bioengineered microorganisms in order to cause harm to people, animals, or plants. | 10.1016/j.vaccine.2009.08.054 |
pubmed_1070_6177 | Lower body mass index (BMI) and lower circulating leptin levels have been reported in girls with AIS. In this paper we evaluate skeletal sizes and asymmetries by higher and lower BMI subsets about the means for each of three groups of girls age 11-18 years: 1) normals, 2) school screening referrals, and 3) preoperative girls. Higher and lower BMI subsets, likely to have separated subjects with higher from those with lower circulating leptin levels, identify: 1) girls with relatively earlier and later menarche; 2) trunk width size greater in the higher than in the lower BMI subset, of all three groups; 3) abnormal upper arm length (UAL) asymmetries (right minus left) in the lower BMI subset of the preoperative girls; and 4) in thoracic AIS of screened and preoperative girls, Cobb angle and apical vertebral rotation each significantly and positively correlate with UAL asymmetry in the lower BMI subset but not in the higher BMI subset. In preoperative girls, the lower BMI subset shows the combination of relatively reduced pelvic width and abnormal UAL asymmetry, suggesting that both are linked to lower circulating leptin levels. An earlier puberty with hormonal changes provides a plausible explanation for the larger trunk width at the shoulders and pelvis especially at the younger ages in the higher BMI subsets. At the shoulders, this widening is driven by the ribcage which, in human evolution was acquired with decoupling of head and trunk movements required for efficient bipedal gait. The UAL asymmetry patterns within the groups and BMI subsets are not explained by hormonal mechanisms. It is hypothesized that 1) normal trunk widening of the thoracic cage by hormones in human adolescence is supplemented via the sympathetic nervous system under leptin-hypothalamic control influenced by energy stores (metabolic fuel); and 2) hypothalamic dysfunction with altered hypothalamic sensitivity to leptin through a SNS-driven asymmetric effect may create skeletal length asymmetries in upper arms, ribs, ilia and vertebrae, and initiate AIS. Additional mechanisms acting in the spine and trunk may be required for AIS to progress including 1) somatic nervous system dysfunction, 2) biomechanical spinal growth modulation, and 3) osteopenia. | pubmed_1070_6177 |
pubmed_1125_15728 | The web-based University of Tokyo Chemical Registration Information System with computational support has been introduced in all areas using chemicals owing to the unified management of the university and the management of chemicals in conformity with legal controls. This system enables chemical users to manage chemicals easily and reduces the burden inflicted by such management. In this report, we introduce the style of chemical management in the University of Tokyo, the functions of the web-based chemical registration system, the current situation of the system and future plans. | pubmed_1125_15728 |
pubmed_1073_24152 | Protein structures can be conceptualized as context-aware self-organizing systems. One of its emerging properties is a modular architecture. Such modular architecture has been identified as domains and defined as its units of evolution and function. However, this modular architecture is not exclusively defined by domains. Also, the definition of a domain is an ongoing debate. Here we propose differentiating structural, evolutionary and functional domains as distinct concepts. Defining domains or modules is confounded by diverse definitions of the concept, and also by other elements inherent to protein structures. An apparent hierarchy in protein structure architecture is one of these elements, where lower level interactions may create noise for the definition of higher levels. Diverse modularity-molding factors such as folding, function, and selection, can have a misleading effect when trying to define a given type of module. It is thus important to keep in mind this complexity when defining modularity in protein structures and interpreting the outcome modularity inference approaches. | 10.2174/1389203716666150923104720 |
pubmed_34_13378 | AIM
To study in in vivo model the efficacy of combined scheme of administration of cancer vaccine (CV) and interferon (IFN).
MATERIALS AND METHODS
Lewis lung carcinoma (LLC) was transplanted to male C57Bl mice. For treatment, CV prepared from LLC cells with the use of cytotoxic lectins of B. subtilis B-7025, and preparation of murine IFN-alpha were used. Therapeutic effect was evaluated by measurement of tumor volume and analysis of average life span (ALS) of treated animals. Immunologic study included determination of antitumor cytotoxicity of T-lymphocytes (CTL) and natural killer (NK) cells by radiometric method, functional activity of peritoneal macrophages (MP) - by colorimetric test with nitroazole blue, and evaluation of titers of tumor necrosis factor (TNF) and interleukins-1 and -2 (IL-1, 2).
RESULTS
It has been shown that the use of IFN preparation significantly elevated efficacy of vaccine therapy of solid form of LLC: duration of latent period of tumor growth elevated by 25%, ALS - by 28%, index of tumor growth inhibition - by 35-40%. Upon combined use of CV and IFN, significant activation of the cells - effectors of nonspecific immune defense (MP), and specific one (CTL) was observed.
CONCLUSION
The obtained results evidence on perspectiveness of the development of combined schemes of administration of CV and IFN for elevation of the efficacy of vaccine therapy. | pubmed_34_13378 |
pubmed_378_11477 | Rotaviruses infect mature, differentiated enterocytes of the small intestine and, by an unknown mechanism, escape the gastrointestinal tract and cause viremia. The neonatal rat model of rotavirus infection was used to determine the kinetics of viremia, spread, and pathology of rotavirus in extraintestinal organs. Five-day-old rat pups were inoculated intragastrically with an animal (RRV) or human (HAL1166) rotavirus or phosphate-buffered saline. Blood was collected from a subset of rat pups, and following perfusion to remove residual blood, organs were removed and homogenized to analyze rotavirus-specific antigen by enzyme-linked immunosorbent assay and infectious rotavirus by fluorescent focus assay or fixed in formalin for histology and immunohistochemistry. Viremia was detected following rotavirus infection with RRV and HAL1166. The RRV 50% antigenemia dose was 1.8 x 10(3) PFU, and the 50% diarrhea dose was 7.7 x 10(5) PFU, indicating that infection and viremia occurred in the absence of diarrhea and that detecting rotavirus antigen in the blood was a more sensitive measure of infection than diarrhea. Rotavirus antigens and infectious virus were detected in multiple organs (stomach, intestines, liver, lungs, spleen, kidneys, pancreas, thymus, and bladder). Histopathological changes due to rotavirus infection included acute inflammation of the portal tract and bile duct, microsteatosis, necrosis, and inflammatory cell infiltrates in the parenchymas of the liver and lungs. Colocalization of structural and nonstructural proteins with histopathology in the liver and lungs indicated that the histological changes observed were due to rotavirus infection and replication. Replicating rotavirus was also detected in macrophages in the lungs and blood vessels, indicating a possible mechanism of rotavirus dissemination. Extraintestinal infectious rotavirus, but not diarrhea, was observed in the presence of passively or actively acquired rotavirus-specific antibody. These findings alter the previously accepted concept of rotavirus pathogenesis to include not only gastroenteritis but also viremia, and they indicate that rotavirus could cause a broad array of systemic diseases in a number of different organs. | 10.1128/JVI.80.10.4820-4832.2006 |
pubmed_835_12640 | AIMS
This study aimed to determine the validity and reliability of the Turkish version of the "Parental Attitudes toward Childhood Vaccines" (PACV) scale.
MATERIALS AND METHODS
A two-stage observational validation study was conducted. A back-translation technique was used and then the scale was validated with a sample of 343 parents with children aged 0-72 months. The test-retest method, Cronbach's alpha coefficient, Split-half analysis, and item analysis methods were used to determine the reliability of the scale, factor analyses were run to determine construct validity. Explanatory Factor Analysis and Confirmatory Factor Analysis were applied to assess construct validity.
RESULTS
Cronbach's alpha coefficient was measured as .84. The Spearman-Brown coefficient was .82 and the Guttman Split-half coefficient was .81. According to the item-total correlation and Cronbach's alpha values when the item was deleted, no item was deleted from the scale. The intraclass correlation coefficient between the test-retest measurements was .79. The three-factor structure consisting of 15 items explained 51.6% of the total variance. As a result of the confirmatory factor analysis, a sufficient fit of the model to the model proposed in the original version of the scale was evident (χ2/sd=2.214, RMSEA=.06).
CONCLUSION
The Turkish version of the PACV is a valid and reliable scale and can be used to identify parental attitudes toward childhood vaccines. | 10.1016/j.jhqr.2022.06.002 |
pubmed_653_9518 | Odorant receptors are thought to play critical roles in the perception of chemosensory stimuli by insects. The primary method to address the functions of odorant receptors in insects is to use in vitro binding assays between the receptors and potential chemical stimuli. We injected MmedOrco dsRNA into the abdominal cavity of a braconid wasp, Microplitis mediator, and assayed for expression of this gene 72 h after treatment (RNAi). Quantitative real-time PCR demonstrated that the level of mRNA expression in MmedOrco dsRNA-treated M. mediator was significantly reduced (>90%) when compared with water-treated controls. Furthermore, electroantennogram (EAG) responses of M. mediator to two chemical attractants, nonanal and farnesene, were also reduced significantly (~70%) in RNAi-treated M. mediator when compared to controls. RNAi-treated M. mediator also responded by walking/flying at a lower rate to both chemicals when compared with controls in a Y-tube olfactometer bioassay, which provides direct evidence that MmedOrco plays an important role in perception of nonanal and farnesene in M. mediator. | 10.1007/s10886-012-0085-y |
pubmed_380_6303 | How can we interact with sedated patients who are seemingly unable to express themselves? On the basis of these questions, we chose to realize a qualitative phenomenological study aimed at comprehending communication with the sedated patient from the perspective of the nurses who take care of those patients. Ten individual interviews were realized with intensive nurses from a Hospital School in S o Paulo. After data analysis, four general thematic categories were revealed: communication with sedated patient x sedation degree; communication with sedated patient x attributed perception capacity; valuation of communication with sedated patient; forms of communication with the sedated patient. This research concluded that the communication with the sedated patient exists and occurs at different moments and in different ways through verbal and non-verbal communication. | pubmed_380_6303 |
pubmed_481_18072 | We study the propagation of intracellular calcium waves in a model that features Ca2+ release from discrete sites in the endoplasmic reticulum membrane and random spatial distribution of these sites. The results of our simulations qualitatively reproduce the experimentally observed behavior of the waves. When the level of the channel activator inositol trisphosphate is low, the wave undergoes fragmentation and eventually vanishes at a finite distance from the region of initiation, a phenomenon we refer to as an abortive wave. With increasing activator concentration, the mean distance of propagation increases. Above a critical level of activator, the wave becomes stable. We show that the heterogeneous distribution of Ca2+ channels is the cause of this phenomenon. | 10.1016/S0006-3495(97)78318-8 |
pubmed_476_3838 | BACKGROUND
Oculo-facio-cardio-dental syndrome is a rare X-linked dominant syndrome, characterized by radiculomegaly, congenital cataracts, dysmorphic facial features, and congenital heart disease. Because of the rarity, this syndrome could be misdiagnosed by the clinician, especially for the infant who may present only one to two systems involved.
CASE PRESENTATION
Here we report a 3-month-old female infant presenting with typical clinical manifestations of oculo-facio-cardio-dental syndrome, like ocular, facial, cardiac, and skeletal abnormalities, and the genetic analyses of the proband and her parents were provided. Genetic evaluations were completed using whole exon sequencing, which revealed a novel heterozygous mutation between exons 7 and 14 of the BCOR gene(OMIM:300485) in this patient but not in her parents. This mutation is likely to encode a premature stop codon producing a truncated protein. Our patient was diagnosed early enough to allow for the cardiac defects to be treated first, and she will be closely followed up to ensure that any new presentations are treated in a timeous manner.
CONCLUSION
This patient fits the diagnostic criteria for oculo-facio-cardio-dental syndrome and is the youngest oculo-facio-cardio-dental syndrome patient ever reported, which is most important for her prognosis. In addition, this manuscript also describes a novel potenitally causative mutation for this syndrome. | 10.1186/s12887-022-03148-x |
pubmed_249_19464 | Protracted administration of diazepam elicits tolerance, whereas discontinuation of treatment results in signs of dependence. Tolerance to the anticonvulsant action of diazepam is present in an early phase (6, 24, and 36 h) but disappears in a late phase (72-96 h) of withdrawal. In contrast, signs of dependence such as decrease in open-arm entries on an elevated plus-maze and increased susceptibility to pentylenetetrazol-induced seizures were apparent 96 h (but not 12, 24, or 48 h) after diazepam withdrawal. During the first 72 h of withdrawal, tolerance is associated with changes in the expression of GABA(A) (gamma-aminobutyric acid type A) receptor subunits (decrease in gamma(2) and alpha(1); increase in alpha(5)) and with an increase of mRNA expression of the most abundant form of glutamic acid decarboxylase (GAD), GAD(67). In contrast, dl-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor GluR1 subunit mRNA and cognate protein, which are normal during the early phase of diazepam withdrawal, increase by approximately 30% in cortex and hippocampus in association with the appearance of signs of dependence 96 h after diazepam withdrawal. Immunohistochemical studies of GluR1 subunit expression with gold-immunolabeling technique reveal that the increase of GluR1 subunit protein is localized to layer V pyramidal neurons and their apical dendrites in the cortex, and to pyramidal neurons and in their dendritic fields in hippocampus. The results suggest an involvement of GABA-mediated processes in the development and maintenance of tolerance to diazepam, whereas excitatory amino acid-related processes (presumably via AMPA receptors) may be involved in the expression of signs of dependence after withdrawal. | 10.1073/pnas.051628698 |
pubmed_944_4297 | BACKGROUND
It is recommended that research in patients with idiopathic scoliosis should focus on short- and long-term patient-centred outcome. The aim of the present study was to evaluate outcome in patients with late-onset juvenile or adolescent idiopathic scoliosis 16 years or more after Boston brace treatment.
METHODS
272 (78%) of 360 patients, 251 (92%) women, responded to follow-up examination at a mean of 24.7 (range 16 - 32) years after Boston brace treatment. Fifty-eight (21%) patients had late-onset juvenile and 214 had adolescent idiopathic scoliosis. All patients had clinical and radiological examination and answered a standardised questionnaire including work status, demographics, General Function Score (GFS) (100 - worst possible) and Oswestry Disability Index (ODI) (100 - worst possible), EuroQol (EQ-5D) (1 - best possible), EQ-VAS (100 - best possible), and Scoliosis Research Society - 22 (SRS - 22) (5 - best possible).
RESULTS
The mean age at follow-up was 40.4 (31-48) years. The prebrace major curve was in average 33.2 (20 - 57)°. At weaning and at the last follow-up the corresponding values were 28.3 (1 - 58)° and 32.5 (7 - 80)°, respectively. Curve development was similar in patients with late-onset juvenile and adolescent start. The prebrace curve increased > 5° in 31% and decreased > 5° in 26%. Twenty-five patients had surgery. Those who did not attend follow-up (n = 88) had a lower mean curve at weaning: 25.4 (6-53)°. Work status was 76% full-time and 10% part-time. Eighty-seven percent had delivered a baby, 50% had pain in pregnancy. The mean (SD) GFS was 7.4 (10.8), ODI 9.3 (11.0), EQ-5D 0.82 (0.2), EQ-VAS 77.6 (17.8), SRS-22: pain 4.1 (0.8), mental health 4.1 (0.6), self-image 3.7 (0.7), function 4.0 (0.6), satisfaction with treatment 3.7 (1.0). Surgical patients had significantly reduced scores for SRS-physical function and self-image, and patients with curves ≥ 45° had reduced self-image.
CONCLUSION
Long-term results were satisfactory in most braced patients and similar in late-onset juvenile and idiopathic adolescent scoliosis. | 10.1186/1748-7161-6-18 |
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