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pubmed_763_9812 | STUDY DESIGN
Clinical, radiological, and genetic determination of zygosity of twin pairs from the Danish Twin Registry who self-reported having adolescent idiopathic scoliosis (AIS).
OBJECTIVE
To establish concordance rates of AIS.
SUMMARY OF BACKGROUND DATA
The etiology of and the true mode of inheritance of AIS remain unclear. Studies on concordance in twin pairs provide a basis for analyzing the influence of genetic versus environmental factors. In 2007, using self-report of AIS from the Danish Twin Registry, concordance rates of 0.13 in monozygotic twins and 0.00 in dizygotic twins were reported.
METHODS
All 46,418 twins registered in the Danish Twin Registry born from 1931 to 1982 were sent a survey, which included questions about scoliosis. The survey was returned by 34,944 individuals (75.3%) representing 23,204 pairs. From the present study, 548 individuals representing 274 complete twin pairs in which at least one twin self-reported having scoliosis were invited to a clinical and radiological examination. Zygosity was established by genetic testing.
RESULTS
A total of 182 individuals (33.2%) of the original cohort agreed to participate, 128 of whom had scoliosis by self-report. There were 91 twin pairs, in which one or both twins had reported scoliosis and 36 individuals whose twin did not want to participate. Only 35 (27%) of the 128 participants with self-reported scoliosis had a clinically and radiologically confirmed curve. Calculating concordance in twins with Cobb angles greater than 10°, we found that the pairwise concordance rate was 0.4 (0.10-0.70) for monozygotic and 0.05 (-0.05-0.15) for dizygotic twins, P = 0.05, probandwise concordance was 0.45 (0.16-0.74) for monozygotic and 0.1 (-0.03-0.23) for dizygotic pairs.
CONCLUSION
Concordance rates in a Danish twin population using genetic testing for zygosity are higher than previously reported using self-report. Although not statistically significant, the differences in monozygotic and dizygotic pairs indicate that genetic factors may be of importance for scoliosis.
LEVEL OF EVIDENCE
3. | 10.1097/BRS.0000000000001681 |
pubmed_547_23640 | Surgical therapy is becoming increasingly complex. Besides new surgical techniques, sophisticated diagnostic methods and innovative interventional procedures must be integrated into the therapeutic concept to increase the efficacy of surgery. Accurate application of these techniques requires close cooperation between surgeons, other medical specialists, and technicians. Consequently, there is a significant need for structures promoting efficient communication, organization, and interaction in surgical departments. New techniques developed from telecommunication and information technology enable the transferal of complex medical data at any time to any place and are therefore the basis for telemedical applications. Telemedicine and other new techniques such as virtual operation planning, simulation, and intraoperative navigation promise to increase the efficacy of surgical therapy in the future. This paper provides an overview of the applications of telesurgery and currently available techniques. | 10.1007/s00104-004-0865-1 |
pubmed_11_6815 | BACKGROUND
Atypical environmental conditions with drought followed by heavy rainfall and flooding in arid areas in sub-Saharan Africa can lead to explosive epidemics of malaria, which might be prevented through timely vector-control interventions.
OBJECTIVES
Wajir County in Northeast Kenya is classified as having seasonal malaria transmission. The aim of this study was to describe in Wajir town the environmental conditions, the scope and timing of vector-control interventions and the associated resulting burden of malaria at two time periods (1996-1998 and 2005-2007).
METHODS
This is a cross-sectional descriptive and ecological study using data collected for routine program monitoring and evaluation.
RESULTS
In both time periods, there were atypical environmental conditions with drought and malnutrition followed by massive monthly rainfall resulting in flooding and animal/human Rift Valley Fever. In 1998, this was associated with a large and explosive malaria epidemic (weekly incidence rates peaking at 54/1,000 population/week) with vector-control interventions starting over six months after the massive rainfall and when the malaria epidemic was abating. In 2007, vector-control interventions started sooner within about three months after the massive rainfall and no malaria epidemic was recorded with weekly malaria incidence rates never exceeding 0.5 per 1,000 population per week.
DISCUSSION AND CONCLUSION
Did timely vector-control interventions in Wajir town prevent a malaria epidemic? In 2007, the neighboring county of Garissa experienced similar climatic events as Wajir, but vector-control interventions started six months after the heavy un-seasonal rainfall and large scale flooding resulted in a malaria epidemic with monthly incidence rates peaking at 40/1,000 population. In conclusion, this study suggests that atypical environmental conditions can herald a malaria outbreak in certain settings. In turn, this should alert responsible stakeholders about the need to act rapidly and preemptively with appropriate and wide-scale vector-control interventions to mitigate the risk. | 10.1371/journal.pone.0092386 |
pubmed_352_16008 | An anatomical reduction is required on both the lateral and AP view. In our hands this is easiest obtained and maintained with the patient in the supine position. The supine position facilitates better anesthesia care in the multiply injured patient and aids in movement of the image intensifer during the procedure. Each step should be carefully followed and the horizontal screw placement is possible only when the image of the holes is perfectly round. When the previously mentioned conditions and steps are followed, a successful locking nail insertion can be achieved. | 10.3928/0147-7447-19851101-09 |
pubmed_219_11738 | We theoretically demonstrate a low crosstalk ring-slot array structure used for label-free multiplexed sensing. The proposed sensors array is based on an array of three ring-slot and input/output line defect coupling waveguides. Each ring-slot cavity has slightly different cavity spacing and different resonant frequency. Results obtained using two dimensional finite-difference time-domain (2D-FDTD) simulation indicate that the resonant frequencies of each sensor unit in response to the refractive index variations are independent. The refractive index sensitivity is 134 ~ 145.5 nm/RIU (refractive index unit) and the Q factors more than 10(4) can be achieved. The calculated detect limit lower than 1.13 × 10(-4) RIU is obtained. In addition, an extremely small crosstalk lower than -25.8 dB is achieved among the array of three ring-slot cavities. The results demonstrate that this multiplexed sensor array is a promising platform for integrated optical devices and enables highly parallel label-free detection. | 10.3390/s140915658 |
pubmed_874_1690 | BACKGROUND
Self-expandable metallic stents (SEMS) are now regarded as an effective and safe intervention for malignant colorectal obstruction (MCO). However, manipulation of the tumor might lead to the spillage of tumor cells and result in distant metastases. We aimed to compare the long-term oncologic outcomes of SEMS as a bridge to surgery with those of emergency surgery for MCO.
METHODS
Between June 2005 and December 2011, 60 patients who underwent elective curative resection after endoscopic SEMS insertion were included in the "SEMS group". The SEMS group was matched to 180 patients who underwent emergency curative surgery for MCO during the same period ["Emergency surgery (ES) group"]. The clinicopathologic characteristics, recurrence-free survival (RFS), and overall survival (OS) were compared between the two groups.
RESULTS
There were no significant differences in demographics, tumor stage, location, and histology between the SEMS group and the ES group. The median follow-up times were 41.4 months (IQR, 22.2-60.0 months) for the SEMS group and 45.0 months (IQR, 20.9-68.1 months) for the ES group. The proportions of patients who received postoperative adjuvant chemotherapy were comparable (SEMS group vs. ES group, 68.3 % vs. 77.8 %; P = 0.210). The long-term prognosis did not significantly differ between two groups in either the 5-year RFS rate (79.6 % vs. 70.2 %; P = 0.218) or the 5-year OS rate (97.8 % vs. 94.3 %; P = 0.469).
CONCLUSIONS
Long-term oncologic outcomes of SEMS insertion as a bridge to surgery were comparable to those of primary curative surgery. | 10.1007/s00464-014-3517-7 |
pubmed_1081_10226 | Dynamic high-pressure appears to be an alternative approach to physical modification of polysaccharides aimed to improve their functional characteristics. The objective of our study was to evaluate the effect of dynamic high-pressure microfluidization (DHPM) treatment on the physicochemical properties and antioxidant activities of Mesona chinensis Benth polysaccharide (MP). The results indicated that the contents of total sugar and uronic acid in DHPM-treated polysaccharide samples (DMP) were increased, and protein content in DMP was significantly decreased after DHPM treatment. The molecular weights of MP and DMP were 1.58 × 105 Da and 1.64 × 105 Da. MP and DMP were composed of Gal, Xyl, and GalA in a molar ratio of 2.8: 5.5: 2.4 and 3.8: 7.4: 3.0, respectively. The antioxidant activities of MP were slightly promoted after DHPM treatment. Moreover, DHPM treatment leads to changes in the morphology of polysaccharide. The surface appearances of DHPM-treated polysaccharide samples showed a slightly curly surface compared to original polysaccharide by SEM analysis. No considerable changes were observed in the structure between the MP and DMP by FT-IR. The results provide useful information for future application of MP, and show DHPM treatment can improve the antioxidant activity of polysaccharides. | 10.1016/j.carbpol.2018.07.087 |
pubmed_601_15898 | Angiotensin I-converting enzyme (ACE, peptidyldipeptide hydrolase, kininase II, EC 3.4.15.I) from human placenta was purified 6297-fold and characterized. ACE could be extensively purified by affinity chromatography with Captopril (D-3-mercapto-2-methylpropanoyl-L-proline), an orally active antihypertensive agent and a potent inhibitor of this enzyme. Its molecular weight and subunit size were estimated to be 300 000 by high-performance gel permeation chromatography and 85 000 by sodium dodecyl sulphate gel electrophoresis, respectively, indicating its polymeric structure. | 10.1016/s0143-4004(85)80008-4 |
pubmed_282_22740 | In arithmetic, rule-violation checking strategies are used while participants solve problems that violate arithmetic rules, like the five rule (i.e., products of problems including five as an operand end with either five or zero; e.g., 5×14=70) or the parity rule (i.e., when at least one of the two operands is even, the product is also even; otherwise the product is odd; e.g., 4×13=52). When problems violate both rules, participants use strategy combination and have better performance on both-rule than on one-rule violation problems (i.e., five or parity rule). Aging studies found that older adults efficiently use one-rule violation checking strategies but have difficulties to combine two strategies. To better understand these aging effects, we used EEG and found important age-related changes while participants used rule-violation checking strategies. We compared participants' performance while they verified arithmetic problems that differ in number and type of violated rule. More specifically, both-rule violation problems elicited larger negativity than one-rule violation problems between 600 and 800ms. Five-rule violation problems differed from parity-rule violation problems between 1100 and 1200ms. Moreover, rule-violation checking strategies and strategy combination involved delta, theta, and lower alpha frequencies. Age-related changes in ERPs and frequency were associated with less efficient strategy combination. Moreover, efficient use of one-rule violation checking strategies in older adults was associated with changes in ERPs and frequency. These findings contribute to further our understanding of age-related changes and invariance in arithmetic strategies, and in combination of arithmetic strategies. | 10.1016/j.ijpsycho.2017.07.003 |
pubmed_322_13244 | BACKGROUND
Oral anticoagulants (OAC) reduce the risk for stroke and death from all causes in patients with non-valvular atrial fibrillation (NVAF).
OBJECTIVES
To explore adherence rates of OAC among patients with NVAF in long-term use in a real-world setting and to examine patient characteristics associated with good adherence.
METHODS
We conducted a population-based cohort study with members of Clalit Health Services, Israel. All patients aged ≥ 30 years with a diagnosis of NVAF before 2016 who were treated with OAC were included. We included patients who filled at least one prescription per year in the three consecutive years 2016-2018. We analyzed all prescriptions that were filled for the medications from 1 January 2017 to 31 December 2017. We considered purchasing of at least nine monthly prescriptions during 2017 as good medication adherence.
RESULTS
We identified 26,029 patients with NVAF who were treated with OAC; 10,284 (39.5%) were treated with apixaban, 6321 (24.3%) with warfarin, 6290 (24.1%) with rivaroxaban, and 3134 (12.0%) with dabigatran. Rates of good medication adherence were 88.9% for rivaroxaban, 84.9% for apixaban, 83.6% for dabigatran, and 55.8% for warfarin (P < 0.0001). Advanced age was associated with higher adherence rates (P < 0.001). Socioeconomic status was not associated with medication adherence. Good adherence with OAC was associated with lower low density lipoprotein (LDL) cholesterol and glucose levels.
CONCLUSIONS
Adherence rates to OAC in chronic use among patients with chronic NAVF are high. Investing in OAC adherence may have a wider health impact than expected. | pubmed_322_13244 |
pubmed_128_2528 | OBJECTIVE
To identify potentially inappropriate prescriptions (PPI) and prescribing omissions (OP) by means of the STOPP/START criteria, as well as associated factors in ≥65year old patients in a Primary Care setting in Spain.
STUDY DESIGN
A cross-sectional, descriptive study.
SETTING
Centro de Salud Monóvar, Primary Health Care.
STUDY PERIOD
6months.
PATIENTS RANDOM SAMPLE
247patients.
ELIGIBILITY CRITERIA
≥65years patients who attended an urban Primary Care clinic 2 or more times were studied. Terminally ill and nursing home residents were excluded.
METHODS
Data were collected from electronic clinical records. STOPP and START criteria were evaluated in each clinical record, including age, sex, co-morbidity, number of chronic prescriptions.
MAIN OUTCOMES
PPI and OP identified by STOPP and START criteria, respectively.
RESULTS
A total of 81 patients (32.8%) had PPI, with the most common being the long-term use of long-acting benzodiazepines in 17 (6.9%). OP was found in 73 (29.6%) patients, with the most common being the omission of statins in patients diagnosed with diabetes mellitus and/or one or more major cardiovascular risk factors in 21 (8.5%). After adjustment by gender and age, correlations were found between PPI and multiple medication (OR: 2.02; 95%CI: 1.15-3.53; P=.014), and OP and polypharmacy (OR: 2.37; 95%CI: 1.32-4.24; P=0.004).
CONCLUSIONS
Inappropriate prescribing in older people is frequent, and is mainly associated with long-acting benzodiazepines. There are diabetic patients who do not have statins prescribed. Multiple medication is associated with PPI and OP. | pubmed_128_2528 |
pubmed_633_19424 | AIMS
Chronic inflammation is linked to type 2 diabetes (T2DM), so we investigated correlations between obesity, blood glucose levels, and inflammation in T2DM patients.
METHODS
Peripheral blood mononuclear cells (PBMCs) were collected from 40 T2DM patients (27 men, 13 women; mean age 49.63 years), and 10 non-diabetic controls (all men; mean age 38.60 years). Inflammation was measured as DNA-binding activity of nuclear factor kappaB (NF-kappaB), a key transcription factor in inflammation. Protein levels of NF-kappaB subunit p65, and NF-kappaB inhibitor IkappaBalpha were assessed by Western blot. Transcript levels for p65, IkappaBalpha, and the NF-kappaB target genes TNF-alpha, MMP-9, IL-6, IL-8, and IL-18 were measured by real-time PCR. Body mass index (BMI) and glycohemoglobin were measured for all the subjects.
RESULTS
NF-kappaB DNA-binding activity, p65 and IkappaBalpha protein levels, and expression of IL-6, TNFalpha and MMP-9 were significantly higher in PBMCs from T2DM patients, than from non-diabetic controls. NF-kappaB binding was significantly positively associated with both BMI and homeostasis model assessment of insulin resistance (HOMA-IR).
CONCLUSIONS
Inflammation was observed in PBMCs in T2DM patients in a Chinese population, and correlated independently with obesity and blood glucose levels. Lack of correlation with glycohemoglobin suggested that moderate-term blood glucose control did not mitigate inflammation. | 10.1016/j.diabres.2010.06.016 |
pubmed_660_15993 | BACKGROUND
Abuse of over-the-counter (OTC) products, such as diet pills and laxatives, for weight control by adolescents is well-documented and can precipitate serious medical conditions. Yet only a small percentage of youth with disordered weight control behaviors receive treatment. The objective of this study was to examine how often clinicians communicate with youth with symptoms consistent with abuse of OTC products for weight control about possible use of these products. We used electronic medical records and administrative claims for services for 53,229 12 to 17 year old patients receiving care from an integrated health system in the U.S. Northwest from August 2007 to December 2010. We examined electronic text of clinical notes to identify encounters in which the clinician noted one of 10 metabolic conditions potentially associated with abuse of OTC products (diet pills, laxatives, diuretics, ipecac, orlistat, and alli®) for weight control and then assessed whether clinicians noted communication with adolescent patients about possible use of OTC products for weight control.
RESULTS
We identified 130 (0.2% of sample) patients with clinical notes indicating one or more of the metabolic conditions. In clinical notes for only four (3.1%) of these patients did clinicians document suspicion or communication about possible abuse of the OTC products. All four had a previous eating disorder diagnosis. In the 12 months subsequent to the clinical encounter in which a metabolic disturbance was identified, medical notes for only three (2.3%) of the 130 patients indicated clinician suspicion or communication about possible abuse of these products or an eating disorder.
CONCLUSIONS
Clinicians are missing a critical window of opportunity to query adolescents when presenting with suspicious metabolic disturbances about possible abuse of OTC products for weight control. Clinicians may need more training to detect OTC product abuse, and electronic medical records should prompt more thorough enquiry. | 10.1186/2050-2974-1-40 |
pubmed_651_13021 | Low affinity mice, prone to chronic immune complex disease (ICD) induced by daily injection of antigen, were fed 0.05% HSA in their drinking water for 7 days before the start of daily injections of HSA. Antigen feeding resulted in a marked decrease in the incidence of ICD despite the presence of high levels of circulating immune complexes. These complexes, which persisted in the circulation for long periods, were of low molecular weight and did not localize in the glomeruli. Antigen fed mice had lower levels of free antibody in their sera compared with control mice which may have favoured the formation of small latticed complexes in antigen excess. Antibody affinity was not apparently affected by prior feeding with antigen. | pubmed_651_13021 |
pubmed_670_18674 | Chemotherapy for colorectal cancer with liver metastases following surgical operation for primary tumor should be selected following surgical intervention. Continuous infusion chemotherapy using an infusional port was selected for unresectable metastasis due to colorectal cancer in our department. The catheter was placed in the hepatic artery through a gastroduodenal by operative procedure. 5-fluorouracil (5-FU) and mitomycin C (MMC) were used as chemotherapeutic agents. After MMC was given at 10 mg/body by bolus, administration of 5-FU was continuously infused at 250 mg/day for 2 weeks, followed by a 2-week interval. Drug administration was done by implanted pump hepatic arterial infusion. Seventeen of the patients with liver metastasis underwent this chemotherapy from 1986 through 1990. Results of the infusion chemotherapy were as follows. Value of serum CEA decreased until two courses were given in all cases. In 11 cases, the tumor size on CT was remarkably smaller. In these patients, however, there were many complications due to the catheter used for catheter replacement, drug leakage, drug extravasation and so on. We concluded that although this chemotherapy was very effective, the method should be improved in terms of the material, the location of catheter tip and the like. | pubmed_670_18674 |
pubmed_759_2296 | Using polyacrylamide-gel electrophoresis, isoelectric focusing and gel-filtration it was demonstrated that the auxotrophic mutant strains of Bac. subtilis A-50 and their prototrophic revertant strains produce multiple molecular forms of subtilisin. Three of them are the same as the corresponding molecular forms of subtilisin from the wild strain A-50. In different mutant strains the relative amounts of the main three forms varies considerably resulting in the absence of certain forms in several strains. There is the additional minor form of subtilisin possessing high electrophoretic mobility in four prototrophic revertant strains and one Arg--auxotrophic strain of Bac. subtilis A-50. It would be reasonable to suppose that different molecular forms of subtilisin derive from the product of its single structural gene as a result of post-translational modifications (limited proteolysis). This enzyme and probably most, if not all secretory proteins may be synthesised as larger precursors and then specifically modified in the bacterial cell membranes. Thus, certain mutations, without affecting the structural gene of this secretory protein -- subtilisin -- have pronounced effects on this structural gene expression, varying the degree of its product modification and the amount of resulting secretory molecular forms of subtilisin. | pubmed_759_2296 |
pubmed_603_25066 | PURPOSE
The aim of this study was to compare the levels of serum immunoglobulin (IgA, IgM, IgG), testosterone and cortisol in semi-endurance elite runners during general preparation and competition phase of training.
METHODS
Thirteen semi-endurance elite male runners with an average age of 18.92±1.7 years volunteered to take part in this study. The runners participated in the selected training for a period of 14 weeks and 12 sessions per week (in the morning and afternoon). Blood samples were collected during the three phases of training (before-preparation phase, after-preparation phase and before-competition phase). Data were analyzed by repeated measures and Bonferroni post hoc test, at a significance level of P<0.05.
RESULTS
The levels of serum IgM in semi-endurance elite runners after preparation phase reduced significantly (P=0.004), while these levels during the competition phase increased even though significantly. The levels of serum IgG and IgA also reduced, however not significantly, during both phases. Moreover, after preparation phase, there was no significant change in serum IgA levels; though, these levels reduced, however not significantly, before competition phase. Cortisol levels significantly decrease after preparation phase (P=0.04); although, it increased before competition phase. Testosterone/cortisol ratio increases significantly after preparation phase (P=0.04), and it decreased before competition phase. Testosterone levels intangibility increased and decreased respectively after preparation and before competition phases.
CONCLUSIONS
Findings indicated that long and intensive exercises weaken the immune system, while moderate and short drills strengthened this system. | pubmed_603_25066 |
pubmed_146_3711 | BACKGROUND
The authors conducted an ultrastructural scanning electron microscopic (SEM) investigation of tissue-engineered pulp constructs implanted within endodontically treated teeth.
METHODS
Stem cells from human exfoliated deciduous teeth were seeded on a synthetic open-cell D,D-L,L-polylactic acid scaffold with or without the addition of bone morphogenic protein-2 and transforming growth factor beta1 to create pulp tissue constructs. The pulp constructs were implanted into 105 extracted human premolar teeth with a single root canal that had been cleaned and shaped by using rotary instrumentation in a crown-down manner to ISO size no. 35.
RESULTS
An ultrastructural examination of the SEM micrographs at x2,000 magnification revealed cell adherence within all of the pulp constructs, with little difference between the scaffold types or with the addition of growth factors.
CONCLUSIONS
These results support the proof-of-concept that it is possible to implant tissue-engineered pulp constructs into teeth after cleaning and shaping.
CLINICAL IMPLICATIONS
Future regenerative endodontic treatment may involve the cleaning and shaping of root canals followed by the implantation of vital dental pulp tissue constructs created in the laboratory. | 10.14219/jada.archive.2008.0189 |
pubmed_881_18904 | There have been presented the data of studying the body functional state of individuals being long contact with the ionizing radiation sources and assessing the effectiveness of prevention and correction of the revealed disorders with the help of adaptogenes. It is found that ordering of eleuterococcus as well as some new biologically active substances which include vitamins amino acids, organic acids, phospholipids, microelements (ammivit, Ascocept, Hianaya) for the course of treatment makes a contribution to a significant, acceleration of adaptation to the extreme factors of the professional activity of the mentioned group of individuals. It is indicated that ammivit, Ascocept and Hianaya out perform eleuterococcus. | pubmed_881_18904 |
pubmed_869_4918 | The regulatory functional nef gene is known to mediate a cascade of events during pathogenesis in HIV infection. Variability in the nef gene sequences of HIV-1 A and B subtypes has been well documented. Reasonable data are also available on the pattern of genomic changes in the nef gene of African strains of HIV-1 subtype C, but very little is known about heterogeneity in the nef gene of Indian strains of HIV-1 subtype C, which accounts for 90% of the estimated 5.2 million cases of HIV infection in India. This is a huge number and, therefore, it is important to reveal the extent of sequence variability in the nef gene of HIV-1 subtypes circulating in different parts of India. We carried out full-length nef gene (approximately 620 bp) sequencing on a large number of clinical isolates of HIV-1 circulating in different geographic regions of India. Comparative and phylogenetic analysis revealed 88% (38/43) of cases was HIV-1 subtype C; four cases were diagnosed as subtype A and only one as subtype B. Although most of the crucial functional motifs of the nef gene were conserved, we did observe a few important variations in juxtapositions to functional domains. Interestingly, analyzed nef sequences showed an evolving pattern of segregation away from those reported from other parts of the world, to form a distinct Indian subclade. Deduced amino acid (aa) sequences used to predict HLA binding epitopes for consensus nef gene sequences of Indian strains of HIV-1 revealed two HLA subtype binding domains, GAFDLSFFL (at aa 83) and LTFGWCFKL (at aa 136), in high frequency. The findings from the present study may encourage use of nef gene in molecular diagnostics/genotyping, keeping track of the evolutionary trend and pinpointing the emergence of recombinant strains, and in the future, designing a multiepitope HIV vaccine suitable for the Indian population. | 10.1089/aid.2006.22.1206 |
pubmed_620_5193 | The concept of operative echography is introduced. A technique of operative ultrasonic bile duct visualization is presented as an alternative to contrast cholangiography during surgery. The technique is rapid, sensitive, provides immediate results, and does not involve the use of ionizing radiation. | 10.1111/j.1445-2197.1979.tb05839.x |
pubmed_946_15308 | Exposed monofilament suture ends caused a variety of symptoms and signs in 18 patients. These included foreign-body sensation, pain, contact lens intolerance, giant papillary conjunctivitis, tarsal ulceration, conjunctival granuloma, corneal infiltrate, and corneal vascularization. These changes followed cataract surgery, corneal transplantation, and pars plana vitrectomy. Diagnoses in these cases were made by careful slit-lamp examination and by eversion of the upper eyelid. In every case, removal of the sutures or trimming the suture ends resulted in the immediate relief of all symptoms with complete resolution of all signs within two months. | 10.1016/0002-9394(83)90274-x |
pubmed_828_20725 | AIM
To study microflora of lower respiratory tract of children from different age groups with cystic fibrosis during follow-up for determination of its variability and possible sources of infectious complications.
MATERIALS AND METHODS
One hundred forty-one medical histories of patients from different age groups with cystic fibrosis living in various regions of Russian Federation were analyzed. Eighty-four children with cystic fibrosis living in Moscow and Moscow region treated as outpatients and inpatients were prospectively followed. For identification and characterization of microorganisms, microbiological, molecular biological, and statistical methods were used.
RESULTS
It was demonstrated that chronic pseudomonas, staphylococcal or mixed infection was already diagnosed in 25% of children aged 1-4 years, and identified in 80% of patients to the age of 18 years. In two-thirds of cases association of microorganisms was identified, and in hospitalized patients these associations were comprised by 3-5 microorganisms in 60% of cases. Aside from main agents in associations (Pseudomonas aeruginosa and Staphylococcus aureus), representatives of Gram-negative nonfermentative microorganisms (Burkholderia cepacia, Stenotrophomonas maltophilia, Acinetobacter baumanii) were often identified that possibly determined by tropism of these species to lung tissue.
CONCLUSION
Chronic mixed infection is characteristic for patients with cystic fibrosis. Identification of possible mechanisms of lung infection in patients with cystic fibrosis will allow to develop evidence-based system of prevention of infectious complications in these patients. | pubmed_828_20725 |
pubmed_715_14589 | The color patterns on the wings of lepidopterans are among the most striking patterns in nature and have inspired diverse biological hypotheses such as the ecological role of aposomatic coloration, the evolution of mimicry, the role of human activities in industrial melanism, and the developmental basis of phenotypic plasticity. Yet, the developmental mechanisms underlying color pattern development are not well understood for three reasons. First, few mutations that alter color patterns have been characterized at the molecular level, so there is little mechanistic understanding of how mutant phenotypes are produced. Second, although gene expression patterns resembling adult color patterns are suggestive, there are few data available showing that gene products have a functional role in color pattern formation. Finally, because with few exceptions (notably Bombyx), genetic maps for most species of Lepidoptera are rudimentary or nonexistent, it is very difficult to characterize spontaneous mutants or to determine whether mutations with similar phenotypes are because of lesions in the same gene or different genes. Discussed here are two strategies for overcoming these difficulties: germ-line transformation of lepidopteran species using transposon vectors and amplified frequency length polymorphism-based genetic mapping using variation between divergent strains within a species or between closely related and interfertile species. These advances, taken together, will create new opportunities for the characterization of existing genetic variants, the creation of new sequence-tagged mutants, and the testing of proposed functional genetic relationships between gene products, and will greatly facilitate our understanding of the evolution and development of lepidopteran color patterns. | 10.1111/j.1525-142X.2005.05012.x |
pubmed_44_10250 | A new mass spectrometric method is proposed for measurement of 234U/238U ratio with a single Daly electron multiplier detector using the general peak jump method. The method is based on precise measurement of the 235U/238U ratio and 234U/235U ratio, which are used to calculate the 234U/238U ratio using the equation 234U/238U = 235U/238U x 234U/235U. The results show a significant improvement, i.e., more than 35 times better precision in measuring the (234)U/(238)U ratio with this method (sigma = 2.9 x 10(-8)) as compared to direct measurement of 234U/238U (sigma = 1.1 x 10(-6)). The method widens the applicability of the single collector system, and it will potentially be helpful to improve the precision in the case of the static multicollector system also. | 10.1021/ac050912p |
pubmed_235_0 | For patients diagnosed with cancer who have previously received an organ transplant, radiotherapy represents a challenging clinical scenario without well established care algorithms. Immunosuppressive therapy can be a cause for concern among clinicians treating this category of patients. Potential immune modulation following irradiation could affect recipient organ tolerance and the outcomes of the transplantation itself. The main aim of this systematic review was to define the safety and effectiveness of radiotherapy in patients diagnosed with cancer who have previously received an organ transplant. We searched PubMed and Embase for articles published between Jan 1, 1995, and April 30, 2020 for studies in patients who had undergone radiotherapy for post-transplantation malignancies. The Review is framed by the PICO (population, intervention, control, and outcomes) criteria, and primarily focuses on modern treatment techniques. | 10.1016/S1470-2045(20)30590-8 |
pubmed_147_23686 | BACKGROUND
Somatic cell nuclear transfer (SCNT) using genetically engineered donor cells is currently the most widely used strategy to generate tailored pig models for biomedical research. Although this approach facilitates a similar spectrum of genetic modifications as in rodent models, the outcome in terms of live cloned piglets is quite variable. In this study, we aimed at a comprehensive analysis of environmental and experimental factors that are substantially influencing the efficiency of generating genetically engineered pigs. Based on a considerably large data set from 274 SCNT experiments (in total 18,649 reconstructed embryos transferred into 193 recipients), performed over a period of three years, we assessed the relative contribution of season, type of genetic modification, donor cell source, number of cloning rounds, and pre-selection of cloned embryos for early development to the cloning efficiency.
RESULTS
109 (56%) recipients became pregnant and 85 (78%) of them gave birth to offspring. Out of 318 cloned piglets, 243 (76%) were alive, but only 97 (40%) were clinically healthy and showed normal development. The proportion of stillborn piglets was 24% (75/318), and another 31% (100/318) of the cloned piglets died soon after birth. The overall cloning efficiency, defined as the number of offspring born per SCNT embryos transferred, including only recipients that delivered, was 3.95%. SCNT experiments performed during winter using fetal fibroblasts or kidney cells after additive gene transfer resulted in the highest number of live and healthy offspring, while two or more rounds of cloning and nuclear transfer experiments performed during summer decreased the number of healthy offspring.
CONCLUSION
Although the effects of individual factors may be different between various laboratories, our results and analysis strategy will help to identify and optimize the factors, which are most critical to cloning success in programs aiming at the generation of genetically engineered pig models. | 10.1186/1472-6750-13-43 |
pubmed_937_12757 | We here report our studies on the conjugation of photoreactive Ru(2+) complex to oligonucleotides (ODNs), which give a stable duplex with the complementary target DNA strand. These functionalized DNA duplexes bearing photoreactive Ru(2+) complex can be specifically photolyzed to give the reactive aqua derivative, [Ru(tpy)(dppz)(H(2)O)](2+)-ODN (tpy = 2,2':6',2' '-terpyridine; dppz = dipyrido[3,2-a:2',3'-c]phenazine), in situ, which successfully cross-links to give photoproduct(s) in the duplex form with the target complementary DNA strand. Thus, the stable precursor of the aquaruthenium complex, the monofunctional polypyridyl ruthenium complex [Ru(tpy)(dppz)(CH(3)CN)](2+), has been site-specifically tethered to ODN, for the first time, by both solid-phase synthesis and postsynthetic modifications. (i) In the first approach, pure 3'-[Ru(tpy)(dppz)(CH(3)CN)](2+)-ODN conjugate has been obtained in 42% overall yield (from the monomer blocks) by the automated solid-phase synthesis on a support labeled with [Ru(tpy)(dppz)Cl](+) complex with subsequent liberation of the crude conjugate from the support under mild conditions and displacement of the Cl(-) ligand by acetonitrile in the coordination sphere of the Ru(2+) label. (ii) In the second approach, the single-modified (3'- or 5'- or middle-modified) or 3',5'-bis-modified Ru(2+)-ODN conjugates were prepared in 28-50% yield by an amide bond formation between an active ester of the metal complex and the ODNs conjugated with an amino linker. The pure conjugates were characterized unambiguously by ultraviolet-visible (UV-vis) absorption spectroscopy, enzymatic digestion followed by HPLC quantitation, polyacrylamide gel electrophoresis (PAGE), and mass spectrometry (MALDI-TOF as well as by ESI). [Ru(tpy)(dppz)(CH(3)CN)](2+)-ODNs form highly stabilized ODN.DNA duplexes compared to the unlabeled counterpart (DeltaT(m) varies from 8.4 to 23.6 degrees C) as a result of intercalation of the dppz moiety; they undergo clean and selective photodissociation of the CH(3)CN ligand to give the corresponding aqua complex, [Ru(tpy)(dppz)(H(2)O)](2+)-ODNs (in the aqueous medium), which is evidenced from the change of their UV-vis absorption properties and the detection of the naked Ru(2+)-ODN ions generated in the course of the matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometric analysis. Thus, when [Ru(tpy)(dppz)(CH(3)CN)](2+)-ODN conjugate was hybridized to the complementary guanine (G)-rich target strand (T), and photolyzed in a buffer (pH 6.8), the corresponding aqua complex formed in situ immediately reacted with the G residue of the opposite strand, giving the cross-linked product. The highest yield (34%) of the photo cross-linked product obtained was with the ODN carrying two reactive Ru(2+) centers at both 3'- and 5'-ends. For ODNs carrying only one Ru(2+) complex, the yield of the cross-linked adduct in the corresponding duplex is found to decrease in the following order: 3'-Ru(2+)-ODN (22%) > 5'-Ru(2+)-ODN (9%) > middle-Ru(2+)-ODN (7%). It was also found that the photo cross-coupling efficiency of the tethered Ru(2+) complex with the target T strand decreased as the stabilization of the resulting duplex increased: 3'-Ru(2+)-ODN (VI.T) (DeltaT(m)(b) = 7 degrees C) < 5'-Ru(2+)-ODN (V.T) (DeltaT(m)(b) = 16 degrees C) < middle-Ru(2+)-ODN (VII.T) (DeltaT(m)(b) = 24.3 degrees C, Table 2). This shows that, with the rigidly packed structure, as in the duplex with middle-Ru(2+)-ODN, the metal center flexibility is considerably reduced, and consequently the accessibility of target G residue by the aquaruthunium moiety becomes severely restricted, which results in a poor yield in the cross-coupling reaction. The cross-linked product was characterized by PAGE, followed by MALDI-TOF MS. | 10.1021/ja0269486 |
pubmed_115_20237 | The American Institute of Ultrasound in Medicine convened a panel of physicians and scientists with interest and expertise in 3-dimensional (3D) ultrasound in obstetrics and gynecology to discuss the current diagnostic benefits and technical limitations in obstetrics and gynecology and consider the utility and role of this type of imaging in clinical practice now and in the future. This conference was held in Orlando, Florida, June 16 and 17, 2005. Discussions considered state-of-the-art applications of 3D ultrasound, specific clinical situations in which it has been found to be helpful, the role of 3D volume acquisition for improving diagnostic efficiency and patient throughput, and recommendations for future investigations related to the utility of volume sonography in obstetrics and gynecology. | 10.7863/jum.2005.24.12.1587 |
pubmed_704_5222 | The COVID-19 epidemic of the novel coronavirus (severe acute respiratory syndrome SARS-CoV-2) has spread around the world. While different containment policies using non-pharmaceutical interventions have been applied, their efficiencies are not known quantitatively. We show that the doubling time T d(t) with the success s factor, the characteristic time of the exponential growth of T d(t) in the arrested regime, is a reliable tool for early predictions of epidemic spread time evolution and provides a quantitative measure of the success of different containment measures. The efficiency of the containment policy lockdown case finding mobile tracing (LFT) using mandatory mobile contact tracing is much higher than that of the lockdown stop and go policy proposed by the Imperial College team in London. A very low s factor was reached by the LFT policy, giving the shortest time width of the positive case curve and the lowest number of fatalities. The LFT policy was able to reduce the number of fatalities by a factor of 100 in the first 100 d of the COVID-19 epidemic, reduce the time width of the COVID-19 pandemic curve by a factor 2.5, and rapidly stop new outbreaks and thereby avoid a second wave to date. | 10.1088/1478-3975/abac51 |
pubmed_234_6945 | Mycoplasma pneumoniae cytadherence is mediated by a specialized, polar attachment organelle. Certain spontaneously arising cytadherence mutants (designated class I) lack HMW2, fail to localize the adhesin protein P1 to the attachment organelle, and exhibit accelerated turnover of proteins HMW1, HMW3, and P65. Insertional inactivation of hmw2 by Tn4001 results in a phenotype nearly identical to that of the class I mutants, suggesting that the latter may result from a defect in hmw2. In this study, the recombinant wild-type hmw2 allele successfully complemented a class I mutant when introduced by transposon delivery. Synthesis of recombinant HMW2 at wild-type levels resulted in reacquisition of hemadsorption and normal levels of HMW1, HMW3, and P65. Low-level production of HMW2 in some transformants resulted in only an intermediate capacity to hemadsorb. Furthermore, full restoration of HMW1 and P65, but not that of HMW3, was directly proportional to the amount of recombinant HMW2 produced, reflecting the importance of proper stoichiometry for certain cytadherence-associated proteins. The recombinant class I hmw2 allele did not restore cytadherence, consistent with a defect in hmw2 in this mutant. A frameshift was discovered in different oligoadenine tracts in hmw2 from two independent class I mutants. Finally, protein P28 is thought to be the product of internal translation initiation in hmw2. A transposon excision-deletion mutant produced a truncated HMW2 but no P28, consistent with this conclusion. However, this deletion mutant was hemadsorption positive, indicating that P28 may not be required for cytadherence. | 10.1128/JB.181.14.4404-4410.1999 |
pubmed_1134_13229 | Phospholipid bilayer interaction of olanzapine (OLZ), a thienobenzodiazepine derivative and an antipsychotic agent, has been studied with (13)C and (31)P solid-state NMR. A dipalmitoyl phosphatidylcholine (60%)/1-palmitoyl-2-oleoyl phosphatidylserine (40%) bilayer (DPPC(60%)/POPS(40%)) with 50 wt.% H(2)O, with and without 10 mol% OLZ have been investigated. The results reveal that both the serine and the choline head groups are affected by OLZ interaction with the bilayer. The OLZ interaction with the serine and the choline head groups appears to be caused by electrostatic attraction to the serine head group carboxyl and repulsion of the choline head group positively charged nitrogen. (31)P MAS NMR experiments show the appearance of two new (31)P resonances both for the PS and the PC phosphorous in the presence of OLZ. Static (31)P NMR spectra demonstrate a decrease in chemical shift anisotropy (CSA) of the OLZ containing bilayer when in the liquid-crystalline phase and an increase in CSA when in the gel state. | 10.1016/j.bpc.2008.01.002 |
pubmed_937_16077 | Signal sequences often contain alpha-helix-destabilizing amino acids within the hydrophobic core. In the precursor of the Escherichia coli outer-membrane protein PhoE, the glycine residue at position -10 (Gly-10) is thought to be responsible for the break in the alpha-helix. Previously, we showed that substitution of Gly-10 by alpha-helix-promoting residues (Ala, Cys or Leu) reduced the proton-motive force dependency of the translocation of the precursor, but the actual role of the helix breaker remained obscure. Here, we considered the possibility that extension of the alpha-helical structure in the signal sequence resulting from the Gly-10 substitutions affects the targeting pathway of the precursor. Indeed, the mutations resulted in reduced dependency on SecB for targeting in vivo. In vitro cross-linking experiments revealed that the G-10L and G-10C mutant PhoE precursors had a dramatically increased affinity for P48, one of the constituents of the signal-recognition particle (SRP). Furthermore, in vitro cross-linking experiments revealed that the G-10L mutant protein is routed to the SecYEG translocon via the SRP pathway, the targeting pathway that is exploited by integral inner-membrane proteins. Together, these data indicate that the helix breaker in cleavable signal sequences prevents recognition by SRP and is thereby, together with the hydrophobicity of the signal sequence, a determinant of the targeting pathway. | 10.1046/j.1432-1033.2002.03262.x |
pubmed_556_23447 | Twenty five percent of the world population is affected by Ascaris lumbricoides. Hepatobiliary ascariasis occurs in areas with high endemicity and great amount of parasitic load, generating intense inflammation to fibrosis. We report a twoyear- old patient that consults about abdominal distension and cough of one month of evolution associated with 72 hours of fever. Abdominal ultrasound is performed, which shows bile duct, stomach, small intestine with ascaris and chest x-ray with interstitial inflammatory infiltrate, associated with hyperleukocytosis with hypereosinophilia and elevated gamma-glutamyl transpeptidase. Antibiotic, anthelminthic treatment is administered, without achieving the elimination of the bile duct parasites, requiring their removal by percutaneous cholangiography. | 10.5546/aap.2020.e476 |
pubmed_839_7896 | Tryptophan residues critical to function are frequently located at the lipid-water interface of transmembrane domains. All members of the epithelial Na+ channel (ENaC)/Degenerin (Deg) channel superfamily contain an absolutely conserved Trp at the base of their first transmembrane domain. Here, we test the importance of this conserved Trp to ENaC/Deg function. Targeted substitution of this Trp in mouse ENaC and rat ASIC subunits decrease channel activity. Differential substitution with distinct amino acids in alpha-mENaC shows that it is loss of this critical Trp rather than introduction of residues having novel properties that changes channel activity. Surprisingly, Trp substitution unmasks voltage sensitivity. Mutant ENaC has increased steady-state activity at hyperpolarizing compared with depolarizing potentials associated with transient activation and deactivation times, respectively. The times of activation and deactivation change 1 ms/mV in a linear manner with rising and decreasing slopes, respectively. Increases in macroscopic currents at hyperpolarizing potentials results from a voltage-dependent increase in open probability. Voltage sensitivity is not influenced by divalent cations; however, it is Na+-dependent with a 63-mV decrease in voltage required to reach half-maximal activity per log increase in [Na+]. Mutant channels are particularly sensitive to intracellular [Na+] for removing this sodium abolishes voltage dependence. We conclude that the conserved Trp at the base of TM1 in ENaC/Deg channels protects against voltage by masking an inhibitory allosteric or pore block mechanism, which decreases activity in response to intracellular Na+. | 10.1074/jbc.M109.015917 |
pubmed_82_18268 | The sid gene promoter (Psid), which controls expression of the late genes from satellite phage P4, is activated by a unique class of small DNA-binding proteins. The activators from both satellite and helper phages stimulate transcription from Psid. These activators bind to sites centered at position -55 in all the helper and satellite phage late promoters. P4 Psid is unique in that it has an additional activator binding site centered at position -18 (site II). We have constructed a mutant of site II that no longer binds activators. Transcription under the control of satellite phage activators is increased by the site II mutation. In contrast, helper phage activators do not show this increase in transcription from Psid mutated at site II. Competition gel shift analysis reveals that the P4 satellite phage activator, Delta, binds eightfold better to site II than to site I. The products of the sid transcription unit are needed only when a helper phage is present; thus, the satellite phage activators repress transcription until the helper is present to supply a nonrepressing activator. | 10.1128/JB.180.19.5151-5158.1998 |
pubmed_1006_6582 | Fasting plasma glucose levels, serum osmolality and serum concentrations of sodium and potassium were determined in 73 Libyan diabetic patients attending the outpatient clinic of the Diabetes Hospital, Tripoli, Libya. The respective mean values were 234.8 +/- 9.7 mg.dl-1, 288.5 +/- 2 m0sm.L-1, 134.7 +/- 0.8 mEq.L-1 and 4.2 +/- 0.07 mEq.L-1. Statistically significant correlations were present between fasting plasma glucose and serum osmolality as well as the concentrations of serum sodium and potassium. There is is an increase in osmolality and levels of sodium and potassium concentration with an increase in plasma glucose concentration. | pubmed_1006_6582 |
pubmed_142_8153 | Colorectal cancer (CRC) worldwide belongs to one of the most frequent cancers affecting both genders. Surgery and 5-fluorouracil-based adjuvant chemotherapy are recommended for patients with high-risk stage II and stage III colon carcinoma. Mutations of genes encoding for specific proteins may have an impact on the time to recurrence. These proteins act over specific signaling pathways, are implicated in metabolic processes and regulate the cell cycle. Though many retrospective studies show strong associations between genetic mutations and the clinical outcome of patients with CRC, currently no validated biomarkers are used in clinical routine settings. Therefore, large prospective validation studies should be carried out in order to strengthen the position of genetic mutations in personalized treatment of patients with CRC. | 10.2217/pgs.15.83 |
pubmed_878_10622 | With growing concern over bacterial resistance, the identification of new antimicrobial means is paramount. In the oral cavity microorganisms are essential to the development of periradicular diseases and are the major causative factors associated with endodontic treatment failure. As quaternary ammonium compounds have the ability to kill a wide array of bacteria through electrostatic interactions with multiple anionic targets on the bacterial surface, it is likely that they can overcome bacterial resistance. Melding these ideas, we investigated the potency of a novel endodontic sealer in limiting Enterococcus faecalis growth. We used a polyethyleneimine scaffold to synthesize nano-sized particles, optimized for incorporation into an epoxy-based endodontic sealer. The novel endodontic sealer was tested for its antimicrobial efficacy and evaluated for biocompatibility and physical eligibility. Our results show that the novel sealer foundation affixes the nanoparticles, achieving surface bactericidal properties, but at the same time impeding nanoparticle penetration into eukaryotic cells and thereby mitigating a possible toxic effect. Moreover, adequate physical properties are maintained. The nanosized quaternary amine particles interact within minutes with bacteria, triggering cell death across wide pH values. Throughout this study we demonstrate a new antibacterial perspective for endodontic sealers; a novel antibacterial, effective and safe antimicrobial means. | 10.1371/journal.pone.0078586 |
pubmed_509_12111 | BACKGROUND
The pig pancreas is considered to be the most suitable source of islets for clinical xenotransplantation. Two types of islet transplantation are: adult pig islets and neonatal porcine islet-like cell clusters (NPCC). However, besides a-Gal expression, differences in glycosylation and xenoantigenicity between both types were not clear so fat to date. In this study, we performed lectin microarray analyses of NPCCs cultured for 1, 5, or 9 days.
METHODS
We studied differences in gycoantigens among several kinds of wild-type NPCCs isolated from 1- to 3-day-old neonatal wild-type pigs (Large White/Landrace × Duroc) and cultured for 1, 5 and 9 days in Ham's 10 in the presence of nicotinamide, using a previously published technique. After sonication and centrifugation, supernatant proteins from each islet were labeled with Cy3, applied to a lectin array and scanned with an SC-Profiler for evaluation using an Array Pro Analyzer.
RESULTS
The overall signals of NPCC at days 5 and 9, showed almost the same values to most lectins, whereas those on day 1 showed differences, suggesting that the NPCC on day 1 contain immature cells that gradually turn to mature NPCCs in culture. | 10.1016/j.transproceed.2012.03.019 |
pubmed_65_15891 | In order to get an insight for designing novel inhibitors of aldose reductase, we analyzed relationships between structures of spiroquinazolinones and their inhibitory activities against rabbit aldose reductase by comparative molecular field analysis and molecular modeling of the enzyme-inhibitor complex. It was revealed that the following interactions were operative for the enhancement of inhibitory activity; 1) the hydrophobic interaction between substituents at the 6'- and 7'-position of quinazolinone and the hydrophobic residues such as Trp20, Val47, Tyr48, Tyr121 and Phe122; 2) the electrostatic interaction formed between electronegative substituents at the 6'-position and the side chain of Gln49; 3) the complementary fit of sterically small 6'-substituents to the active site. | pubmed_65_15891 |
pubmed_1059_74 | The construct validity of aniseikonic lens measures of anxiety as a personality trait and of anxiety toward objects was examined in an experimental setting. No evidence of convergent construct validity was found for aniseikonic measures of anxiety as a personality trait. The validity of such measures as indices of anxiety toward objects was also questioned. The findings suggested that familiarity with the object viewed, rather than anxiety, may be the underlying dimension tapped by such measures of ability to perceive aniseikonic distortion. | 10.2466/pms.1976.43.3.915 |
pubmed_866_25689 | We compared the incidence of refractory thrombocytopenia (RT) and platelet transfusion requirements (PTR) in 35 children who developed veno-occlusive disease (VOD) with 35 matched control subjects who underwent hematopoietic stem cell transplant but did not develop VOD. RT developed in 100% of the VOD patients, at a median of 8 days before VOD diagnosis, as compared with 71.5% of the control group. VOD patients required more platelet transfusions than control subjects (median PTR, 6.9 mL/kg [range, .57 to 17.59] versus 3.57 mL/kg [range, 0 to 14.63], respectively) with a statistically significant difference (P < .0001). The number of days with platelet requirements was significantly higher for VOD patients as compared with control subjects (median 68% versus 39%, P =< .0001). The PTR peaked at ~12 mL/kg/day, 2 days before VOD diagnosis, whereas the PTR in the control population was 5 mL/kg/day. The positive predictive value of developing VOD was 88.9% (95% confidence interval, 66.5% to 97%) in patients who were given >7 mL/kg/day of platelets during the at-risk period of days +3 to +13 after transplant. For patients who received >8 mL/kg/day of platelets, the positive predictive value of developing VOD was 86.7% (95% confidence interval, 61.2% to 96.4%). There was no difference in the PTR in patients with mild to moderate VOD as compared with severe VOD; however, the PTR was higher in patients whose VOD did not resolve. The median daily PTR after the diagnosis of VOD in 17 patients who got defibrotide as compared with those who did not get defibrotide was 6.04 mL/kg and 5.72 mL/kg, respectively, but the difference was not statistically significant (P = .56). On univariate and multivariate analysis use of intravenous immunoglobulin was significantly associated with VOD (P = .0088) but was not significantly associated with fatal VOD. In conclusion, RT occurs in 100% of patients at a median of 8 days before VOD diagnosis. VOD should be suspected in any patient with RT after the exclusion of other causes of consumptive thrombocytopenia, especially if they require >7 mL/kg/day of platelets. | 10.1016/j.bbmt.2019.11.012 |
pubmed_322_15017 | Brain tumors are an abnormal growth of cells in the brain, also known as multifactorial groups of neoplasm. Incidence rates of brain tumors increase rapidly, and it has become a leading cause of tumor related deaths globally. Several factors have potential risks for intracranial neoplasm. To date, the International Agency for Research on Cancer has classified the ionizing radiation and the N-nitroso compounds as established carcinogens and probable carcinogens respectively. Diagnosis of brain tumors is based on histopathology and suitable imaging techniques. Labeled amino acids and fluorodeoxyglucose with or without contrast-enhanced MRI are used for the evaluation of tumor traces. T2-weighted MRI is an advanced diagnostic implementation, used for the detection of low-grade gliomas. Treatment decisions are based on tumor size, location, type, patient's age and health status. Conventional therapeutic approaches for tumor treatment are surgery, radiotherapy and chemotherapy. While the novel strategies may include targeted therapy, electric field treatments and vaccine therapy. Inhibition of cyclin-dependent kinase inhibitors is an attractive tumor mitigation strategy for advanced-stage cancers; in the future, it may prove to be a useful targeted therapy. The blood-brain barrier poses a major hurdle in the transport of therapeutics towards brain tissues. Moreover, nanomedicine has gained a vital role in cancer therapy. Nano drug delivery system such as liposomal drug delivery has been widely used in the cancer treatment. Liposome encapsulated drugs have improved therapeutic efficacy than free drugs. Numerous treatment therapies for brain tumors are in advanced clinical research. | 10.1016/j.biopha.2021.112119 |
pubmed_269_13609 | Photosynthetic carbon fixation is fundamental for plant growth and is a key process driving the global carbon cycle. This study explored the mechanism of disturbed carbon fixation in Oryza sativa L. by organic pollutants 2,3,4,5-tetrachlorobiphenyl (CB 61), 4'-hydroxy-2,3,4,5-tetrachlorobiphenyl (4'-OH-CB 61), 2,2',4,4'-tetrabromo diphenyl ether (BDE 47), tricyclazole (TRI), and pyrene. The biomass of rice exposed to 4'-OH-CB 61, TRI, and BDE 47 was on average 80.63% of that of the control (p < 0.05), and the inhibition of net photosynthetic rate was 59.15% by 4'-OH-CB 61. Proteomics confirmed that 4'-OH-CB 61 significantly downregulated the enzymes in the photosynthetic carbon fixation pathway, which was attributed to the decrease in ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco), the rate-limiting enzyme in the Calvin cycle. In detail, decreased Rubisco activity (6.96-33.44%) and downregulated OsRBCS2-5 encoding small Rubisco subunits (-6.80 < log2FC < -2.13) by 4'-OH-CB 61, TRI, and BDE 47 were in line with biomass yield reduction. Molecular docking and dynamic simulation suggested that the three pollutants potentially competed with CO2 for binding to the active sites in Rubisco, leading to reduced CO2 capture efficiency. These results revealed the molecular mechanism of organic pollution-induced rice yield reduction, contributing to improving the understanding of crop growth and carbon sequestration capacity of organics-contaminated soils globally. | 10.1021/acs.est.1c07835 |
pubmed_390_13575 | Brown adipose tissue (BAT) thermogenic activity has been measured in lactating rats on day 11 post-partum. In order to assess the response of this tissue to different rates of milk production, litter sizes were adjusted to give 2, 4, 8 or 12 pups/dam. In all lactating animals, BAT mass and protein content were markedly reduced, but thermogenic activity was only fully suppressed in dams nursing large litters. In those with 4 pups, guanosine diphosphate-binding activity (expressed as pmol GDP bound/mg mitochondrial protein) was lower than that of virgin control rats, but remained well above values obtained from control animals acclimated at thermoneutrality. Other estimates of BAT thermogenesis, cytochrome oxidase activity and noradrenaline-stimulated increase in oxygen consumption supported the inverse relationship between litter size and BAT function. Possible control mechanisms for the observed changes in BAT activity in lactating animals are discussed. | 10.1159/000176789 |
pubmed_271_23744 | Plaque rupture plays a role in the majority of acute coronary syndromes. Rupture has usually been associated with stress concentrations, which are mainly affected by the plaque geometry and the tissue properties. The aim of this study is to evaluate the influence of morphology on the risk of plaque rupture, including the main geometrical factors, and to assess the role of circumferential and axial residual stresses by means of a parametric 3D finite element model. For this purpose, a 3D parametric finite element model of the coronary artery with eccentric atheroma plaque was developed. Healthy (adventitia and media in areas without atheroma plaque) and diseased (fibrotic and lipidic) tissues were considered in the model. The geometrical parameters used to define and design the idealized coronary plaque anatomy were the lipid core length, the stenosis ratio, the fibrous cap thickness, and the lipid core ratio. Finally, residual stresses in longitudinal and circumferential directions were incorporated into the model to analyse the influence of the important mechanical factors in the vulnerability of the plaque. Viewing the results, we conclude that residual stresses should be considered in the modelling of this kind of problems since they cause a significant alteration of the vulnerable plaque region limits. The obtained results show that the fibrous cap thickness and the lipid core length, in combination with the lipid core width, appear to be the key morphological parameters that play a determinant role in the maximal principal stress (MPS). However, the stenosis ratio is found to not play a significant role in vulnerability related to the MPS. Plaque rupture should therefore be observed as a consequence, not only of the cap thickness, but as a combination of the stenosis ratio, the fibrous cap thickness and the lipid core dimensions. | 10.1007/s10237-011-0369-0 |
pubmed_713_13863 | Parkinson's disease (PD) is a neurodegenerative disorder characterized by motor dysfunction. Recent studies have shown that curcumin (CUR) has neuroprotective effects in PD experimental models. However, its efficacy is limited due to low water solubility, bioavailability, and access to the central nervous system. In this study, we compared the effects of new curcumin-loaded nanoemulsions (NC) and free CUR in an experimental model of PD. Adult Swiss mice received NC or CUR (25 and 50 mg/kg) or vehicle orally for 30 days. Starting on the eighth day, they were administered rotenone (1 mg/kg) intraperitoneally until the 30th day. At the end of the treatment, motor assessment was evaluated by open field, pole test, and beam walking tests. Oxidative stress markers and mitochondrial complex I activity were measured in the brain tissue. Both NC and CUR treatment significantly improved motor impairment, reduced lipoperoxidation, modified antioxidant defenses, and prevented inhibition of complex I. However, NC was more effective in preventing motor impairment and inhibition of complex I when compared to CUR in the free form. In conclusion, our results suggest that NC effectively enhances the neuroprotective potential of CUR and is a promising nanomedical application for PD. | 10.1007/s12640-021-00362-w |
pubmed_1023_2779 | Urinary D-lactate excretion, expressed as the molar D-lactate/creatinine ratio, was measured serially in nine term and premature infants with necrotizing enterocolitis, 15 healthy term infants, and eight term and premature infants sick but without NEC. The mean (+/- SD) uDL/CR of the infants with NEC was 1.63 +/- 1.09, significantly greater than the mean uDL/CR of the healthy infants (0.16 +/- 0.04) or the sick infants without NEC (0.43 +/- 0.32). The uDL/CR of infants with NEC rose coincident with the onset of disease, reached peak values at an average of 5.8 days, and subsided to baseline levels on recovery. Seven of the nine infants with NEC reached or exceeded a peak uDL/CR of 1.47; no infant without NEC reached this ratio. We conclude that uDL/CR is increased in infants with NEC and demonstrates the increased enteric bacterial activity in this disease. | 10.1016/s0022-3476(84)81010-0 |
pubmed_308_4559 | The inorganic layered crystal (ILC) MoS2 in low dimensions is considered as one of the most promising and efficient semiconductors. To enable the magnetism and keep intrinsic crystal structures, we carried out a first-principles study of the magnetic and semiconductive monolayer MoS2 adsorbed with the Mnn (n = 1-4) clusters, and bilayer MoS2 intercalated with the same clusters. Geometric optimizations of the Mnn@MoS2 systems show the complexes prefer to have Mnn@MoS2(M) pizza and Mnn@MoS2(B) sandwich forms in the mono- and bi-layered cases, respectively. Introductions of the clusters will enhance complex stabilities, while bonds and charge transfers are found between external Mn clusters and the S atoms in the hosts. The pizzas have medium magnetic moments of 3, 6, 9, 4 μB and sandwiches of 3, 2, 3, 2 μB following the manganese numbers. The pizzas and sandwiches are semiconductors, but with narrower bandgaps compared to their corresponding pristine hosts. Direct bandgaps were found in the Mnn@MoS2(M) (n = 1,4) pizzas, and excitingly in the Mn1@MoS2(B) sandwich. Combining functional clusters to the layered hosts, the present work shows a novel material manipulation strategy to boost semiconductive ILCs applications in magnetics. | 10.1038/srep19504 |
pubmed_988_1504 | The aim of our study was to evaluate the best method for cervical ripening before a classical induction with amniotomy and oxytocin. One hundred term pregnant patients who presented an unfavorable cervix and an indication for the induction of labor were assigned randomly to either 0.5 mg prostaglandin (PG) E2 gel intracervically (N = 52) or 3 mg PGE2 gel intravaginally (N = 48). The intravaginal gel had a greater effect on cervical ripening according to a modification of the Bishop score than did intracervical gel, but it had a higher incidence of side effects. | pubmed_988_1504 |
pubmed_897_18741 | Nitric oxide (NO) is a diatomic free radical produced from L-arginine by constitutive and inducible nitric oxide synthase (cNOS and iNOS) in numerous mammalian cells and tissues. Nitric oxide (NO), superoxide (O2-) and their reaction product peroxynitrite (ONOO-) may be generated in excess during the host response against viral and antibacterial infections and contribute to some pathogenesis by promoting oxidative stress, tissue injury and, even, cancer. Oxidative damage, caused by action of free radicals, may initiate and promote the progression of a number of chronic diseases, including cancer, cardiovascular diseases, Alzheimer's disease, diabetes and inflammation. The mechanism of inflammation injury is attributed, in part, to release of reactive oxygen species from activated neutrophils and macrophages. ROS propagate inflammation by stimulating release of mediators such as NO and cytokines. The interest of the research is motivated by the current need to find new substances of natural origin which have demonstrated effectiveness in the described fields of application and low degree of toxicity for humans. Natural products provide a vast pool of NO inhibitors that can possibly be developed into clinical products. This article reviews some plenolic secondary metabolites from plants with NO inhibitory properties and their structure-activity relationship studies that can be focused for drug development programs. | 10.2174/092986711795029690 |
pubmed_163_17 | BACKGROUND
Intravenous propacetamol is commonly used to control fever and pain in neurocritically ill patients in whom oral administration is often difficult. However, several studies reported that intravenous propacetamol may cause blood pressure drop. Thus, we aimed to investigate the occurrence and risk factors for intravenous propacetamol-induced blood pressure drop in neurocritically ill patients.
METHODS
This retrospective study included consecutive patients who were administered intravenous propacetamol in a neurointensive care unit at a single tertiary academic hospital between April 2013 and June 2020. The exact timing of intravenous propacetamol administration was collected from a database of the electronic barcode medication administration system. Blood pressure drop was defined as a systolic blood pressure below 90 mm Hg or a decrease by 30 mm Hg or more. Blood pressure, pulse rate, and body temperature were collected at baseline and within 2 h after intravenous propacetamol administration. The incidence of blood pressure drop was evaluated, and multivariable logistic regression analysis was performed to identify risk factors for blood pressure drop events.
RESULTS
A total of 16,586 instances of intravenous propacetamol administration in 4916 patients were eligible for this study. Intravenous propacetamol resulted in a significant decrease in systolic blood pressure (baseline 131.1 ± 17.8 mm Hg; within 1 h 124.6 ± 17.3 mm Hg; between 1 and 2 h 123.4 ± 17.4 mm Hg; P < 0.01). The incidence of blood pressure drop events was 13.5% within 2 h after intravenous propacetamol. Older age, lower or higher baseline systolic blood pressure, fever, higher Acute Physiology and Chronic Health Evaluation II score, and concomitant administration of vasopressors/inotropes or analgesics/sedatives were significant factors associated with the occurrence of blood pressure drop events after intravenous propacetamol administration.
CONCLUSIONS
Intravenous propacetamol can induce hemodynamic changes and blood pressure drop events in neurocritically ill patients. This study identified the risk factors for blood pressure drop events. On the basis of our results, judicious use of intravenous propacetamol is warranted for neurocritically ill patients with risk factors that make them more susceptible to hemodynamic changes. | 10.1007/s12028-021-01390-2 |
pubmed_1006_226 | The human immunodeficiency virus (HIV) proteins gp120 and gp41 are the principal immune target in HIV infection. One of the most important trends in the study of AIDS is linked to the mapping of sites involving in the binding to the cell receptor CD4 and in the induction of virus-neutralizing antibodies (VNA). Recent studies have revealed that gp120 as the major domain contains inducing type-specific BNA (PND) and a binding region with CD4 (CD4-BR). PND is located in the hypervariable loop of gp120 (residues 301-336 for a BRU strain), and CD4-BR is in the conservation area (residues 410-450). By using the synthetic fragments from these areas (BRU and MN strains) and HIV-infected persons' sera, the authors established that the immune response to PND and CD4-BR is somewhat interrelated: there is a synchronized response of HIV antibodies to peptides from the two regions in ELISA (r = 0.82). For analysis of this phenomenon, experiments with cross-linked immunoreactivity of rabbit antisera to peptides from PND and CD4-BR with homologous and heterologous peptides were performed by applying three control peptides from HIV and hepatitis B virus. It has been found that there is a cross reactivity between rabbit anti-PND (MN, BRU) and anti-CD4-BR abs. Peptide homological analysis revealed common structural elements for PND and CD4-BR despite significant differences in their proposed functions. There is a large amount of positively charged aa within both PND and CD4-BR which may be involved in gp120-CD4 interaction. Acetylation of Lys residues resulted in complete loss of peptide reactivity. | pubmed_1006_226 |
pubmed_681_66 | This manuscript reviewed the neurotoxicity of dioxins and related compounds with an emphasis on maternal exposure. The brain during developmental period is thought to be highly sensitive to dioxin and its related compounds that affect a broad range of brain functions from the advanced brain function to the reproduction-controlling function, even at low doses. It is suggested that dioxins exhibit endocrine-disrupting action on the gonadal and thyroid hormone axes, as well as the 'neural-disrupting action' on neural transmission and neural network formation. From behavioral toxicological studies as well as studies on the underlying mechanisms of dioxins' toxicity, dioxins affect some specific functions in particular regions or cells of the brain at critical windows during the developmental period. | 10.2486/indhealth.41.215 |
pubmed_1095_3752 | This study examined the incidence of extreme sensory modulation behaviors in toddlers with autism spectrum disorders (ASD) and investigated the consistency of sensory information across measures. Parent report of sensory behaviors in 101 toddlers with ASD was compared with 100 toddlers who were typically developing matched on chronological age and 99 additional infants or toddlers matched on mental age. Measures included the Infant/Toddler Sensory Profile, Infant-Toddler Social Emotional Assessment, Autism Diagnostic Interview-Revised, and Autism Diagnostic Observation Schedule-Generic. Toddlers with ASD were most distinct from typically developing groups in their high frequency of underresponsiveness and avoiding behaviors and their low frequency of seeking. Within the toddlers with ASD, there were significant associations across sensory parent report measures, but parent report was not correlated with clinical observation. Findings point to the early onset of an extreme sensory profile in ASD. Occupational therapists need to assess multiple domains of sensory behaviors to accurately identify the needs of toddlers with ASD. | 10.5014/ajot.61.5.584 |
pubmed_661_15719 | Physostigmine-induced pressor response was studied in adrenalectomized rats. The increase in mean arterial blood pressure elicited by intravenous administration of physostigmine was not altered by adrenalectomy or sham-operation. The pressor response to intracerebroventricular administration of physostigmine was found to be partially inhibited in both acutely adrenalectomized and sham-operated rats, but not in those adrenalectomized 24 h earlier. This inhibition was completely prevented by naloxone pretreatment. The results suggest that endogenous opioid peptide release induced by surgical stress may be responsible for inhibition of the pressor effect of centrally administered physostigmine in rats. | 10.3109/13813458709104526 |
pubmed_1061_19862 | Methylparaben and triclosan are antimicrobial agents widely used as preservatives in a variety of personal care and pharmaceutical products. Wastewater is considered the main source of these compounds in the environment. Expanded granular sludge bed (EGSB) reactors are a high rate technology for wastewater treatment based on biological processes and have been shown to be efficient in removing different types of compounds; however, little is known about the effect of contaminants such as methylparaben and triclosan on their behavior and effectiveness. In this study, we evaluate and compare the microbial and physicochemical behavior of EGSB systems during methylparaben and triclosan removal. The presence of different concentrations of pollutants had an influence on the cluster organization of microbial communities, especially bacteria. However, this did not affect the stability and performance of the EGSB systems. The banding patterns of the denaturing gradient gel electrophoresis of archaea demonstrated the constant presence and abundance of Methanosaeta concilii throughout all stages of operation, showing that this microorganism played a fundamental role in the stability of the reactors for the production of methane. The type of compound and its concentration influenced the expression of the mcrA and ACAs genes; however, these changes did not alter the stability and performance of the EGSB systems. | 10.2166/wst.2019.293 |
pubmed_126_5334 | The personality functioning of adults diagnosed with attention deficit disorder (ADD) without comorbid psychiatric illness was examined. NEO PI-R profiles in a group of 25 adults referred for ADD evaluation meeting criteria for this diagnosis without any history of other psychiatric disturbance were compared to profiles from a control group of 23 nonpsychotic adult outpatients being treated with psychotherapy. All participants completed self-report measures of ADD symptoms as well as the NEO PI-R (Form S). The ADD adult group obtained significantly higher scores in the Neuroticism domain and significantly lower scores in the Conscientiousness domain than the outpatient comparison group. The NEO PI-R appears useful to the understanding of ADD in adulthood. | 10.1177/107319119800500104 |
pubmed_139_7358 | A glycolipid with blood group A activity detected in the non-epithelial stroma of normal rat colon but not in epithelial cells (Hansson, G.C., Karlsson, K.-A., and Thurin, J. (1984) Biochim. Biophys. Acta 792, 281-292), was purified to homogeneity from normal rat colon and rat colon adenocarcinoma. Mass spectrometry and 1H-NMR spectroscopy of the intact permethylated derivative and gas chromatography after degradation revealed the structure GalNAc alpha 1----3GAINAc beta 1----3Gal alpha 1----3Gal beta 1----4Glc beta 1----1Cer, with the predominant ceramide containing sphingosine and non-hydroxylated 24:0 fatty acid. This identifies this glycolipid as a novel Forssman-like glycolipid, which is a tumor-associated antigen by definition, since it is not present in the normal rat large intestinal epithelium cells but in rat adenocarcinoma derived from these cells. | 10.1016/0005-2760(86)90161-x |
pubmed_273_21600 | Nasoalveolar cysts are uncommon nonodontogenic and developmental cysts with an uncertain pathogenesis. This cyst has been reported to occur bilaterally in 10-11% of cases. This case report describes a 45-year-old woman in whom the clinicopathologic findings were consistent with bilateral nasoalveolar cysts. The authors report a new, less invasive method for transnasal endoscopic marsupialization of bilateral nasoalveolar cysts. Transnasal endoscopic marsupialization has benefits for the treatment of bilateral and unilateral nasoalveolar cysts. | 10.1016/j.ijom.2009.06.012 |
pubmed_856_24955 | Apolipoprotein E (ApoE), an important mediator of lipid transportation in plasma and the nervous system, plays a large role in diseases such as atherosclerosis and Alzheimer's. The major allele variants ApoE3 and ApoE4 differ only by one amino acid. However, this difference has major consequences for the physiological behaviour of each variant. In this paper, we follow (i) the initial interaction of lipid-free ApoE variants with model membranes as a function of lipid saturation, (ii) the formation of reconstituted High-Density Lipoprotein-like particles (rHDL) and their structural characterisation, and (iii) the rHDL ability to exchange lipids with model membranes made of saturated lipids in the presence and absence of cholesterol [1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) or 1-palmitoyl-2-oleoyl-glycero-3-phosphocholine (POPC) with and without 20 mol% cholesterol]. Our neutron reflection results demonstrate that the protein variants interact differently with the model membranes, adopting different protein conformations. Moreover, the ApoE3 structure at the model membrane is sensitive to the level of lipid unsaturation. Small-angle neutron scattering shows that the ApoE containing lipid particles form elliptical disc-like structures, similar in shape but larger than nascent or discoidal HDL based on Apolipoprotein A1 (ApoA1). Neutron reflection shows that ApoE-rHDL do not remove cholesterol but rather exchange saturated lipids, as occurs in the brain. In contrast, ApoA1-containing particles remove and exchange lipids to a greater extent as occurs elsewhere in the body. | 10.3389/fchem.2021.630152 |
pubmed_290_18397 | Gully erosion is a dominant source of sediment and particulates to the Great Barrier Reef (GBR) World Heritage area. We selected the Bowen catchment, a tributary of the Burdekin Basin, as our area of study; the region is associated with a high density of gully networks. We aimed to use a semi-automated object-based gully networks detection process using a combination of multi-source and multi-scale remote sensing and ground-based data. An advanced approach was employed by integrating geographic object-based image analysis (GEOBIA) with current machine learning (ML) models. These included artificial neural networks (ANN), support vector machines (SVM), and random forests (RF), and an ensemble ML model of stacking to deal with the spatial scaling problem in gully networks detection. Spectral indices such as the normalized difference vegetation index (NDVI) and topographic conditioning factors, such as elevation, slope, aspect, topographic wetness index (TWI), slope length (SL), and curvature, were generated from Sentinel 2A images and the ALOS 12-m digital elevation model (DEM), respectively. For image segmentation, the ESP2 tool was used to obtain three optimal scale factors. On using object pureness index (OPI), object matching index (OMI), and object fitness index (OFI), the accuracy of each scale in image segmentation was evaluated. The scale parameter of 45 with OFI of 0.94, which is a combination of OPI and OMI indices, proved to be the optimal scale parameter for image segmentation. Furthermore, segmented objects based on scale 45 were overlaid with 70% and 30% of a prepared gully inventory map to select the ML models' training and testing objects, respectively. The quantitative accuracy assessment methods of Precision, Recall, and an F1 measure were used to evaluate the model's performance. Integration of GEOBIA with the stacking model using a scale of 45 resulted in the highest accuracy in detection of gully networks with an F1 measure value of 0.89. Here, we conclude that the adoption of optimal scale object definition in the GEOBIA and application of the ensemble stacking of ML models resulted in higher accuracy in the detection of gully networks. | 10.3390/s19224893 |
pubmed_365_9519 | Sequential changes in small separated texture elements can produce perception of a moving form with continuous boundaries. This process of spatiotemporal boundary formation may exist to provide a robust means of detecting moving objects that occlude more distant textured surfaces. Whereas most research on spatiotemporal boundary formation has been focused on boundary and shape perception, two experiments are reported here on the perception of surface qualities in spatiotemporal boundary formation. In experiment 1 a free-report procedure was used to investigate whether surface perception can be determined by dynamic information alone, apart from static spatial differences. Results showed that dynamic information was sufficient to determine the appearance of a surface. This dynamic information may play an important role in other aspects of perception. In experiment 2, it was shown that dynamically specifying an extended, opaque surface facilitated edge perception. Implications for the relation of boundary and surface perception and for theories of perceptual transparency are discussed. | 10.1068/p270403 |
pubmed_709_4471 | In this review, the new aluminum-formaldehyde (ALFA) histofluorescence method for the highly sensitive visualization of monoamine-containing neurones in adult and immature central nervous tissue is summarized. Animals are first perfused with a buffer containing high concentrations of aluminum ions and the brains are then freeze-dried, reacted with formaldehyde vapour and further processed according to the Falck-Hillarp fluorescence method. The ALFA technique applied to adult brains visualizes all known catecholamine neurone systems with a sensitivity comparable to, and for certain noradrenergic systems higher than, that of the previously published glyoxylic acid-Vibratome method. The catecholamine systems in immature brains are demonstrated with a sensitivity clearly superior to that of any other available method. If the ALFA method is combined with systemic injections of alpha-methylnoradrenaline into young animals (less than one week old), there is a dramatic increase in the intensity and number of catecholaminergic fibres. Many catecholaminergic systems which have too low concentrations of transmitter to be visualized in the untreated animal even with the ALFA method, can be demonstrated after administration of alpha-methylnoradrenaline. The use of freeze-dried, paraffin-embedded tissue in the ALFA method makes possible convenient storage and parallel processing of many specimens. This mode of processing also allows en bloc reaction, which is the only way by which consistent and reproducible fluorescence yields can be obtained throughout large series of sections and parallel-processed specimens. In animals pretreated with L-tryptophan and monoamine oxidase-inhibitor, the technique is also useful for studies on central indolamine-containing systems. | 10.1007/BF01002712 |
pubmed_295_22016 | Bacteria produce a huge diversity of metabolites, many of which mediate ecological relations. Among these, volatile compounds cause broad-range effects at low doses and, therefore, may be exploited for plant defence strategies and agricultural production, but such applications are still in their early development. Here, we review the latest technologies involving the use of bacterial volatile compounds for phytosanitary inspection, biological control, plant growth promotion, and crop quality. We highlight a variety of effects with a potential applicative interest, based on either live biocontrol and/or biostimulant agents, or the isolated metabolites responsible for the interaction with hosts or competitors. Future agricultural technologies may benefit from the development of new analytical tools to understand bacterial interactions with the environment. | 10.1016/j.tplants.2021.05.006 |
pubmed_299_21912 | BACKGROUND
Computerized decision support systems (CDSSs) are information technology-based software that provide health professionals with actionable, patient-specific recommendations or guidelines for disease diagnosis, treatment, and management at the point-of-care. These messages are intelligently filtered to enhance the health and clinical care of patients. CDSSs may be integrated with patient electronic health records (EHRs) and evidence-based knowledge.
METHODS/DESIGN
We designed a pragmatic randomized controlled trial to evaluate the effectiveness of patient-specific, evidence-based reminders generated at the point-of-care by a multi-specialty decision support system on clinical practice and the quality of care. We will include all the patients admitted to the internal medicine department of one large general hospital. The primary outcome is the rate at which medical problems, which are detected by the decision support software and reported through the reminders, are resolved (i.e., resolution rates). Secondary outcomes are resolution rates for reminders specific to venous thromboembolism (VTE) prevention, in-hospital all causes and VTE-related mortality, and the length of hospital stay during the study period.
DISCUSSION
The adoption of CDSSs is likely to increase across healthcare systems due to growing concerns about the quality of medical care and discrepancy between real and ideal practice, continuous demands for a meaningful use of health information technology, and the increasing use of and familiarity with advanced technology among new generations of physicians. The results of our study will contribute to the current understanding of the effectiveness of CDSSs in primary care and hospital settings, thereby informing future research and healthcare policy questions related to the feasibility and value of CDSS use in healthcare systems. This trial is seconded by a specialty trial randomizing patients in an oncology setting (ONCO-CODES).
TRIAL REGISTRATION
ClinicalTrials.gov, https://clinicaltrials.gov/ct2/show/NCT02577198?term=NCT02577198&rank=1. | 10.1186/s13012-016-0455-x |
pubmed_49_10687 | The majority of male C57Bl/Rij mice died infected with Plasmodium berghei early in the second week. Death was closely correlated to collapse of the thermoregulation of the body, with perivascular oedema and petechial haemorrhages in the brain. Mice that did not show a collapse of thermoregulation (temperature drop below 30 degrees C) and survived for more than 2 weeks after infection did not show haemorrhages. Development of this syndrome (temperature below 30 degrees C; early death; haemorrhages) during infection depended on the presence of the spleen and was prevented by irradiation of the spleen or a timely treatment with dexamethasone, anti-T-cell serum or immune serum. | pubmed_49_10687 |
pubmed_686_19835 | Stool specimens from 124 international travelers with acute diarrhea were tested for the presence of enteropathogens. Noroviruses (NoVs) were the second most commonly identified enteric pathogen in diarrheal stool samples (21/124, 17%), exceeded only by enterotoxigenic Escherichia coli (50/106, 47%). This study indicates that NoV is an underappreciated cause of traveler's diarrhea. | 10.1128/JCM.43.12.6126-6129.2005 |
pubmed_821_7569 | OBJECTIVE
To study alteration of several genes in the process of primary lung cancer.
METHODS
A series of 59 lung cancer specimens were analyzed for p53, myc oncogene family and mdrl gene by DNA/PCR sequencing, immunohistochemistry and RT-PCR methods.
RESULTS
p53 mutation or/and protein accumulation were found in 37 of 57(65%) cases. Overexpression of myc family oncogenes and mdr1 gene were 27/46 (59%) and 15/48 (31%), respectively. The results also showed that there was no significant correlation between p53 alteration and tumor size, metastasis, stage and relapse, but there was a significant correlation between overexpression of myc family oncogene and these factors. Overexpression of mdrl gene was detected in NSCLC, especially in adenocarcinoma, and was not associated with metastasis and stage of lung cancer. It was also found that aberration of both p53 and myc family oncogenes occurred in 19/30(63%) cases; the relapse rate was 76%. Both overexpression of mdrl and myc gene was 62%; the relapse rate was 83%.
CONCLUSION
p53, myc and mdrl genes in cooperation may be involved in the process of lung cancer, but prognostic determinant is myc gene overexpression. | pubmed_821_7569 |
pubmed_269_2935 | We recently identified a missense mutation in Nucleoporin107 (Nup107; D447N) underlying XX-ovarian-dysgenesis, a rare disorder characterized by underdeveloped and dysfunctional ovaries. Modeling of the human mutation in Drosophila or specific knockdown of Nup107 in the gonadal soma resulted in ovarian-dysgenesis-like phenotypes. Transcriptomic analysis identified the somatic sex-determination gene doublesex (dsx) as a target of Nup107. Establishing Dsx as a primary relevant target of Nup107, either loss or gain of Dsx in the gonadal soma is sufficient to mimic or rescue the phenotypes induced by Nup107 loss. Importantly, the aberrant phenotypes induced by compromising either Nup107 or dsx are reminiscent of bone morphogenetic protein (BMP signaling hyperactivation). Remarkably, in this context, the metalloprotease AdamTS-A, a transcriptional target of both Dsx and Nup107, is necessary for the calibration of BMP signaling. As modulation of BMP signaling is a conserved critical determinant of soma-germline interaction, the sex- and tissue-specific deployment of Dsx-F by Nup107 seems crucial for the maintenance of the homeostatic balance between the germ cells and somatic gonadal cells. | pubmed_269_2935 |
pubmed_546_491 | Health care restructuring efforts have been influenced by changes in public policy, payment mechanisms, and societal values. In today's environment, leading issues focus on quality and cost-effective care. Health care systems are moving from a concentration on structures and processes of care to an expanded view that encompasses the exploration, documentation, and improvement of patient outcomes. This article presents an overview of the domains of health outcomes, widely used surveys in the measurement of outcomes, methodological issues related to interpreting outcome measures, and trends for clinical practice and future research. | 10.1097/00004479-199710000-00007 |
pubmed_491_2704 | BACKGROUND
Inaccurate use of International Classification of Diseases, Ninth Revision (ICD-9), codes obfuscates registries used for research, resulting in unreliable data and inaccurate measurement of outcomes, and it may contribute to mismanagement of patients. Thus it is important to understand the prevalence of ICD-9 code misuse. We chose chronic kidney disease (CKD) as a condition of interest after several patients recruited for a previous study indicated they did not have the disease, despite the presence of the ICD-9 code (585.x) in their electronic medical record (EMR).
METHODS
Retrospective chart review of patients with the ICD-9 code for CKD stage 3 (585.3; n = 325). Data were collected from EMRs at 3 primary care practices Buffalo, New York (n = 2), and Kansas City, Kansas (n = 1).
RESULTS
Across all practices, 47% of patients with the CKD ICD-9 code did not have clinical indicators for the disease, based on Kidney Disease Outcomes Quality Initiative guidelines.
CONCLUSIONS
The CKD stage 3 ICD-9 code usage did not accurately reflect the prevalence of disease among this population. This has clinical implications because patients may be treated or receive tests for a disease they do not have. This also presents an important issue for research projects that rely on accurate data from EMRs to identify and recruit patients. | 10.3122/jabfm.2015.05.140136 |
pubmed_806_7772 | Large efforts dedicated to detect somatic alterations across tumor genomes/exomes are expected to produce significant improvements in precision cancer medicine. However, high inter-tumor heterogeneity is a major obstacle to developing and applying therapeutic targeted agents to treat most cancer patients. Here, we offer a comprehensive assessment of the scope of targeted therapeutic agents in a large pan-cancer cohort. We developed an in silico prescription strategy based on identification of the driver alterations in each tumor and their druggability options. Although relatively few tumors are tractable by approved agents following clinical guidelines (5.9%), up to 40.2% could benefit from different repurposing options, and up to 73.3% considering treatments currently under clinical investigation. We also identified 80 therapeutically targetable cancer genes. | pubmed_806_7772 |
pubmed_591_3853 | Hordeum vulgare (barley) hordoindolines (HINs), HINa, HINb1, and HINb2, are orthologous proteins of wheat puroindolines (PINs) that are small, basic, cysteine-rich seed-specific proteins and responsible for grain hardness. Grain hardness is, next to its protein content, a major quality trait. In barley, HINb is most highly expressed in the mid-stage developed endosperm and is associated with both major endosperm texture and grain hardness. However, data required to understand the spatio-temporal dynamics of HIN transcripts and HIN protein regulation during grain filling processes are missing. Using reverse transcription quantitative PCR (RT-qPCR) and proteomics, we analyzed HIN transcript and HIN protein abundance from whole seeds (WSs) at four [6 days after pollination (dap), 10, 12, and ≥20 dap] as well as from aleurone, subaleurone, and starchy endosperm at two (12 and ≥20 dap) developmental stages. At the WS level, results from RT-qPCR, proteomics, and western blot showed a continuous increase of HIN transcript and HIN protein abundance across these four developmental stages. Miroscopic studies revealed HIN localization mainly at the vacuolar membrane in the aleurone, at protein bodies (PBs) in subaleurone and at the periphery of starch granules in the starchy endosperm. Laser microdissetion (LMD) proteomic analyses identified HINb2 as the most prominent HIN protein in starchy endosperm at ≥20 dap. Additionally, our quantification data revealed a poor correlation between transcript and protein levels of HINs in subaleurone during development. Here, we correlated data achieved by RT-qPCR, proteomics, and microscopy that reveal different expression and localization pattern of HINs in each layer during barley endosperm development. This indicates a contribution of each tissue to the regulation of HINs during grain filling. The effect of the high protein abundance of HINs in the starchy endosperm and their localization at the periphery of starch granules at late development stages at the cereal-based end-product quality is discussed. Understanding the spatio-temporal regulated HINs is essential to improve barley quality traits for high end-product quality, as hard texture of the barley grain is regulated by the ratio between HINb/HINa. | 10.3389/fpls.2018.00775 |
pubmed_461_5751 | The ergonometric methods used in the organization of the medical personnel of stomatological establishments and in designing technical facilities of stomatological rooms help raise the effectiveness of the therapeutic processes and to improve conditions of work of the physician-stomatologist and medical nurses. At the basis of modern ergonomic facilities and principles in stomatology there are the concepts: recumbent patient, sitting medical personnel, invariable presence of an assisting nurse, "long-term" treatment and centralization of the ancillary service. | pubmed_461_5751 |
pubmed_1025_161 | 1. Aldosterone is a hormone that affects both blood pressure and glucose homeostasis. We studied the association of the aldosterone synthase gene (CYP11B2) polymorphism -344T>C with essential hypertension (EH) and glucose homeostasis in people in China. 2. We investigated the polymorphism -344T>C in CYP11B2 using a case-control study design (1059 cases and 1120 controls). Genotyping was carried out by matrix-assisted laser desorption/ionization time-of-flight mass spectroscopy using a MassARRAY platform. 3. The aldosterone synthase gene -344T>C polymorphism was found to be associated with EH (odds ratio 1.252; 95% confidence interval 1.067-1.468; P(add) = 0.006). The -344C variant was found to be significantly associated with increased systolic blood pressure (P(add) = 0.003) and diastolic blood pressure (P(add) = 0.024) in controls and increased plasma aldosterone levels (P(add) = 0.0001) in EH cases. The -344C variant was also found to be significantly associated with increased fasting glucose (P(rec) = 0.003) in controls. In the subgroup containing 893 EH cases without a history of diabetes or hypoglycaemia medications, the -344C variant was found to be associated with increased fasting and postprandial plasma glucose levels (P(add) = 0.0001, P(add) = 0.001, respectively) and decreased pancreatic β-cell function and insulin sensitivity (P(add) = 0.030, P(dom) = 0.019, respectively) by homeostasis model assessments. 4. In this Han Chinese population, the -344T/C polymorphism of the CYP11B2 gene was found to be associated with EH and glucose homeostasis, both of which might be mediated by plasma aldosterone levels, insulin sensitivity and β-cell function. | 10.1111/j.1440-1681.2011.05555.x |
pubmed_828_22061 | BACKGROUND
The overall consumption of trans fatty acids (TFAs) increases the risk of coronary artery disease. However, multiple TFA isomers exist, each with potentially different health effects. Different food sources of these specific TFA isomers are not well established.
OBJECTIVE
Our objective was to determine the major independent food sources of specific TFA isomers.
DESIGN
We investigated relations of major potential food sources of TFAs, as assessed by serial food-frequency questionnaires, with 10 plasma phospholipid TFA isomers [5 trans (t-) 18:1, 3 t-18:2, and 2 t-16:1] in 3330 older adults in the Cardiovascular Health Study, a community-based multicenter cohort. Stepwise regression was used to identify independent major food sources of individual plasma phospholipid TFA isomers, which were adjusted for demographic, lifestyle, and dietary factors.
RESULTS
All 5 t-18:1 isomers were similarly associated with foods commonly made with partially hydrogenated vegetable oils (PHVOs), including biscuits (0.51 higher SD of total 18:1 fatty acid concentrations per serving/d, P < 0.01), chips and/or popcorn (0.33 higher SD per serving/d, P = 0.02), margarine (0.32 higher SD per serving/d, P < 0.001), fried foods (0.32 higher SD per serving/d, P = 0.04), and bakery foods (0.23 higher SD per serving/d, P = 0.02). Each of the t-18:2 isomers were associated only with bakery foods (0.50 higher SD of total 18:2 fatty acid concentrations per serving/d, P < 0.001). Ruminant foods were major correlates of t-16:1n-7, including red meats (0.72 higher SD per serving/d, P < 0.001), butter (0.43 higher SD per serving/d, P < 0.001), and higher-fat dairy (0.37 higher SD per serving/d, P < 0.001). In contrast, t-16:1n-9 were derived mainly from margarine (0.31 higher SD per serving/d, P < 0.001).
CONCLUSIONS
t-18:1 Isomers are similarly derived from multiple PHVO-containing foods. In contrast, t-18:2 and t-16:1n-9 isomers are derived from more-specific types of PHVO-containing foods. Ruminant foods are major sources of t-16:1n-7. Different TFA isomers and dietary sources should be considered when investigating health effects and interventions to lower TFAs. | 10.3945/ajcn.2009.28877 |
pubmed_872_1006 | The purpose of this study was to investigate the effect of dose on norfloxacin pharmacokinetics and distribution into the brain extracellular fluid (ECF), in freely moving rats. Unbound concentrations of norfloxacin in hippocampus were determined by microdialysis after an i.v. bolus dose of 12.5, 25, 50, 100, or 150 mg/kg in rats. In vivo recovery of norfloxacin was determined by retrodialysis by calibrator. Among three fluoroquinolones (enoxacin, pefloxacin, and ciprofloxacin) selected as potential calibrators, ciprofloxacin was selected as the best one. Maximum ECF brain norfloxacin concentrations are rapidly obtained but the ECFbrain/plasma areas under curves (AUC) ratios are low and independent of dose with a mean value of 8.2 +/- 5.8%. By contrast, norfloxacin systemic pharmacokinetics was nonlinear, with total plasma clearance decreasing significantly from 23.0 +/- 3.4 to 14.4 +/- 3.8 mL/min/kg when dose increased from 12.5 to 150 mg/kg. | 10.1002/jps.10504 |
pubmed_324_12851 | Principal Component Analysis (PCA) is a statistical process monitoring technique that has been widely used in industrial applications. PCA methods for Fault Detection (FD) use data collected from a steady-state process to monitor T(2) and Q statistics with a fixed threshold. For the systems where transient values of the processes must be taken into account, the usage of a fixed threshold in PCA method causes false alarms and missing data that significantly compromise the reliability of the monitoring systems. In the present article, a new PCA method based on variance sensitive adaptive threshold (T(vsa)) is proposed to overcome false alarms which occur in the transient states according to changing process conditions and the missing data problem. The proposed method is implemented and validated experimentally on an electromechanical system. The method is compared with the conventional monitoring methods. Experimental tests and tabulated results confirm the fact that the proposed method is applicable and effective for both the steady-state and transient operations and gives early warning to operators. | 10.1016/j.isatra.2010.12.004 |
pubmed_803_1657 | Arteriovenous fistula as a complication of the Seldinger procedure is infrequent. 2 cases of arteriovenous fistula are described, both developed after simultaneous ipsilateral femoral artery and vein catheterization. Possible etiological factors are discussed. | pubmed_803_1657 |
pubmed_426_2641 | As judged by its ability to stimulate glucose uptake and alpha-aminoisobutyric acid (AIB) transport, the sensitivity and the responsiveness of perfused rat muscle to insulin are enhanced after moderately intense treadmill exercise. In fed rats, these enhanced effects of insulin are predominantly restricted to muscles that performed work as evidenced by glycogen depletion. The present study was designed to examine the relationship between glycogen depletion per se and the postexercise changes in insulin action. Toward this end, fed and 48-h starved rats were run on a treadmill for 45 min at moderate intensity, and glucose and AIB uptake were then assessed using the isolated perfused hindquarter preparation. Glycogen is depleted in red muscles such as the soleus and red fibers of the gastrocnemius in fed rats immediately after such exercise, whereas, in starved rats, muscle glycogen is unchanged. As previously shown, the stimulation by insulin of glucose utilization by the hindquarter and AIB transport into red muscles was substantially increased in fed rats after the treadmill run. This was due to increases in both insulin sensitivity and responsiveness. In starved rats, the treadmill run also enhanced the ability of insulin to stimulate these processes; however, this was solely due to an increase in insulin sensitivity. No change in insulin responsiveness was observed. The results indicate that the enhanced sensitivity of muscle to insulin after exercise is not dependent on glycogen depletion, whereas increased insulin responsiveness does not occur in its absence. They also suggest that the mechanisms by which prior exercise acts to increase insulin sensitivity and responsiveness are different. | 10.1152/ajpendo.1986.251.6.E664 |
pubmed_708_8261 | Twenty-seven kinds of organic dye-inactivated Sendai virus vaccines were prepared by treatment in dark at 23 C for 2 months or more, and selected with the high HA titers as a guide. Their nasal immunogenicities were examined in mice by contact infection and immunofluorescent method, and the relative merits of the dye-inactivants were determined. The strongest protection was elicited with acriflavine-, auramine O-, eosin Y-, neutral red-, night blue-, patent blue V-, thymol blue-, uranin-, and xylene cyanol FF-treated vaccines. Middling protective efficacy was induced by use of erio green B-, malachite green-, methyl green-, proflavine-, pyronin B-, and thionin-inactivated vaccines. Dye-inactivated vaccines that resulted in the weakest protection were Bindschedler's green-, bromothymol blue-, erythrosin B-, ethyl violet-, gallein-, light green SF yellowish-, methyl violet-, new methylene blue N-, phenol red-, rhodamine 6G-, spirit blue- and victoria blue B-treated ones. Serum HI titers developed by nasal vaccination were variable, and rose still more in most vaccinated groups postexposure. Elicitation of the most effective nasal immunogenicity in dye-inactivated vaccines appeared to depend on selective modification of capsid protein or ribose in viral core with dyes possessing definite functions, despite the different molecular structures. | 10.1111/j.1348-0421.1990.tb01017.x |
pubmed_1104_11192 | Peroxisome assembly in mammals requires more than 14 genes. So far, we have isolated seven complementation groups (CGs) of peroxisome biogenesis-defective Chinese hamster ovary (CHO) cell mutants, Z65, Z24/ZP107, ZP92, ZP105/ZP139, ZP109, ZP110, ZP114. Two peroxin cDNAs, PEX2 and PEX6, were first cloned by genetic phenotype-complementation assay using Z65 and ZP92, respectively, and were shown to be responsible for peroxisome biogenesis disorders (PBD) such as Zellweger syndrome, of CG-F (the same as CG-X in U.S.A.) and CG-C (the same as CG-IV), respectively. Pex2p is a RING zinc finger membrane protein of peroxisomes and Pex6p is a member of the AAA ATPase family. We likewise isolated PEX12 encoding a peroxisomal integral membrane protein in the RING family, by functional complementation of ZP109, demonstrating PEX12 to be responsible for CG-III PBD. We also cloned PEX1 by screening of human liver cDNA library, using ZP107. PEX1 mutation was delineated to be the genetic cause of PBD in the most highest incidence group, CG-E (the same as CG-I). Moreover, we recently found that Pex5p is involved in transport of not only PTS1- but also PTS2-protein, distinct from yeast Pex5p, using PEX5-defective ZP105 and ZP139. Thus, CHO cell mutants defective in peroxisome biogenesis are indeed shown to be very useful for the studies of peroxisome assembly and delineating pathogenic genes in PBD. Furthermore, we have isolated novel CGs of CHO mutants, ZP119 and ZP126. | 10.1385/cbb:32:1-3:155 |
pubmed_937_10730 | Primary small cell carcinoma of the urinary bladder is a highly aggressive disease and accounts for less than 0.5% of all primary bladder tumors. Quite often, clinical presentation is related to local and/or systemic involvement of the disease. Histogenesis is still unknown, but investigators consider the tumor originating from a multipotent undifferentiated stem cell of the bladder urothelium. Hematuria is the first and most frequent symptom that patients complain at the clinical presentation of the disease. The primary local tumor is treated by radical surgery or radiation therapy, while systemic involvement requires polychemotherapy according to the M-VAC protocol. Prognosis is worse and related to the pathological stage of the disease and to chemotherapy reply. Herein we report on 3 cases of primary small cell carcinoma of the urinary biadder. We also review and update the literature concerning this topic. | pubmed_937_10730 |
pubmed_527_4782 | Osteochondral lesions in children mainly occur in the physeal and epiphyseal cartilage. Osteochondritis dissecans and osteochondrosis (apophysitis) are common and clinically important chronic disorders. These etiology and pathogenesis have also been well investigated in the Veterinary medicine in recent years. One of the most likely causes is proposed as a failure of blood supply to growth cartilage and following focal disturbance of endochondral ossification. Mechanical stress, trauma, rapid growth, anatomic conformation, and dietary imbalances would modify this initial step and break down the normal structure. In human, above-mentioned pathological changes can be detected using recent MRI technology, which contribute quite much in the early diagnosis of lesions in clinic. Another problem in children is acute traumatic growth plate injury, which increases the risk of the early closure of growth plate and following deformity of bone and joint. Early diagnosis and precise treatment are extremely important for children to prevent residual deformity and pain and growth disturbance. In future, less-invasive as well as effective treatments for the focally disturbed or accelerated ossification should be developed. | CliCa1006849858 |
pubmed_618_14531 | Fluorescence spectra from individual aerosol particles that were either coated or embedded with metallic nanoparticles (MNPs) was acquired on-the-fly using 266 nm and 355 nm excitation. Using aqueous suspensions of MNPs with either polystyrene latex (PSL) spheres or dissolved proteins (tryptophan or ovalbumin), we generated PSL spheres coated with MNPs, or protein clusters embedded with MNPs as aerosols. Both enhanced and quenched fluorescence intensities were observed as a function of MNP concentration. Optimizing MNP material, size and spacing should yield enhanced sensitivity for specific aerosol materials that could be exploited to improve detection limits of single-particle, on-the-fly fluorescence or Raman based spectroscopic sensors. | 10.1364/OE.22.018966 |
pubmed_874_15390 | BACKGROUND
Newer strategies for augmenting immune responses of pharmacologically active glucans may serve to improve the medicinal potential of these biomolecules. With this aim, the present work was focused on generating targeted high molecular size glucan particles with magnified immune response activity.
METHODS
Heteroglucans were conjugated with PAMAM dendrimers using a Schiff base reductive amination reaction to generate a polytethered molecule with multiple glucan motifs. The modulated construct was characterized by FTIR, TEM, (1)H NMR and dynamic light scattering (DLS) methods. Effects of conjugated glucans were examined in RAW 264.7 macrophage cells as well as in S-180 murine tumor models.
RESULTS
Dendrimer-conjugated glucans were found to exhibit a two-fold increase in immune stimulation in comparison to unconjugated glucans. This may be corroborated by the predominant enhancement in immunological functions such as nitric oxide production, ROS generation and immune directed tumor inhibition in murine models. Immune cell surface markers (CD4, CD8, CD19, MHC-II) and cytokine levels were also found to be highly up-regulated in the splenocytes of mice subjected to particulate glucan administration. Our study also demonstrated that conjugated glucan treatment to RAW 264.7 cells strongly enhanced the phosphorylation of two downstream signalling molecules of the mitogen activated protein kinase (MAPKs) family: p38 and MEK1/2 relative to single glucans thereby relating molecular mechanisms with enhanced immune stimulation.
CONCLUSIONS AND GENERAL SIGNIFICANCE
The results obtained thus support that particulate format of soluble heteroglucan will thereby improve its functionality and identify leads in therapeutic competence. | pubmed_874_15390 |
pubmed_329_24530 | Glucocorticoids are primary therapy of idiopathic nephrotic syndrome (INS). However, not all children respond to steroid therapy. We assessed glomerular glucocorticoid receptor expression in fifty-one children with INS and its relation to response to steroid therapy and to histopathological type. Clinical, laboratory and glomerular expression of glucocorticoid receptors were compared between groups with different steroid response. Glomerular glucocorticoid expression was slightly higher in controls than in minimal change early responders, which in turn was significantly higher than in minimal change late responders. There was significantly lower glomerular glucocorticoid receptor expression in steroid-resistance compared to early responders, late responders and controls. Glomerular glucocorticoid expression was significantly higher in all minimal change disease (MCD) compared to focal segmental glomerulosclerosis. In INS, response to glucocorticoid is dependent on glomerular expression of receptors and peripheral expression. Evaluation of glomerular glucocorticoid receptor expression at time of diagnosis of NS can predict response to steroid therapy. | 10.1080/15513815.2016.1225872 |
pubmed_257_15638 | As an antiproliferative strategy, we are using bis(ethyl) derivatives of spermine to suppress polyamine biosynthetic enzyme activity and, thereby, deplete intracellular polyamine pools. Since certain of these analogues have recently been shown to potently increase spermidine/spermine-N1-acetyltransferase activity, we have investigated the relationship of this effect to growth inhibition and polyamine depletion. The cellular effects of N1,N12-bis(ethyl)spermine (BESPM) and two of its homologues, N1,N11-bis(ethyl)norspermine (BENSPM) and N1,N14-bis(ethyl)homospermine (BEHSPM), were compared in L1210 cells following treatments at equimolar concentrations (2 microM) and at concentrations (0.5 microM BEHSPM; 2 microM BESPM, and 20 microM BENSPM) producing comparable intracellular concentrations (2600-3000 pmol/10(6) cells) of the analogues. At 2 microM, BENSPM increased total polyamine N-acetyltransferase activity by 15-fold, BESPM, by 7-fold, and BEHSPM, by only 1.5-fold. These differences were much more exaggerated at comparable intracellular concentrations, where BENSPM increased enzyme activity 31-fold, BESPM, 7-fold, and BEHSPM had no effect. This rank order in effectiveness sharply contrasted effects on cell growth and interference with polyamine biosynthesis, which correlated more with intracellular accumulation of the analogues. At 2 microM, BEHSPM was most effective in suppressing ornithine and S-adenosylmethionine decarboxylases, depleting polyamine pools, and inhibiting cell growth, followed by BESPM and then by BENSPM. Thus, the data indicate that, in L1210 cells, the large increases in spermidine/spermine-N1-acetyltransferase activity produced by the analogues do not appear to contribute significantly to polyamine depletion or to be causally related to inhibition of cell growth. These studies also identify BENSPM as the most potent modulator of spermidine/spermine-N1-acetyltransferase activity thus far studied in cell culture systems. To a large extent, its greater effectiveness over BESPM seems to be attributable to a major increase in prolongation of enzyme half-life (3.9 versus 1.3 h), presumably due to enzyme stabilization caused by differential binding of the analogues at the enzyme active site. | pubmed_257_15638 |
pubmed_579_12696 | Mechanically durable stretchable trans-istors are fabricated using carbon nanotube electrical components and tough thermoplastic elastomers. After an initial conditioning step, the electrical characteristics remain constant with strain. The strain-dependent characteristics are similar in orthogonal stretching directions. Devices can be impacted with a hammer and punctured with a needle while remaining functional and stretchable. | 10.1002/adma.201501828 |
pubmed_921_5743 | BACKGROUND
Effectiveness of antitumor drugs to suppress unrestricted proliferation of cancer cells is commonly measured by cell clonogenicity assays. Assays of clonogenicity are also used in studies of stem/progenitor cells and in analysis of carcinogenic transformation. The conventional assays are limited to providing information about frequency of colonies (cloning efficiency) and do not reveal the qualitative (phenotype) attributes of individual colonies that may yield clues on mechanisms by which cell proliferation was affected by the studied agent.
METHODS
Laser scanning cytometry (LSC) was adapted to identify and characterize size and phenotype of colonies of MCF-7 cells growing in microscope slide chambers, untreated and treated with the cytotoxic ribonuclease, onconase (Onc). Individual colonies were located and data representing each colony were segmented based on >650-nm fluorescence excited by a He-Ne laser of the cells whose protein was stained with BODIPY 630/650-X. The DNA of the cells was stained with propidium iodide (red fluorescence) whereas specific proteins (estrogen receptor [ER] or tumor suppressor p53) were detected immunocytochemically (green fluorescence), each excited by an Ar ion laser.
RESULTS
A plethora of attributes of individual colonies were measured, such as (a) morphometric features (area, circumference, area/circumference ratio, DNA or protein content per area ratio), (b) number of cells (nuclei), (c) DNA content, (d) protein content and protein/DNA ratio, and (e) expression of ER or p53 per colony, per total protein, per nucleus or per DNA, within a colony. Also cell cycle distribution within individual colonies and heterogeneity of colonies with respect to all the measured features could be assessed. The colonies growing in the presence of Onc had many of the above attributes different than the colonies from the untreated cultures.
CONCLUSIONS
Analysis of the features of cell colonies by LSC provides a wealth of information about the progeny of individual cells. Changes in colony size and phenotype, reflecting altered cell shape, cell size, colony protein/DNA ratio, and expression of individual proteins, may reveal mechanisms by which drugs suppress the proliferative capacity of the cells. This may include inducing growth imbalance and differentiation and modulating expression of the genes that may be associated with cell cycle, apoptosis, or differentiation in a progeny of individual cells. Extensions of LSC may make it applicable for automatic analysis of cloning efficiency and multiparameter analysis of cell colonies in soft agar. Such analyses may be useful in studies of the mechanisms and effectiveness of antitumor drugs, in the field of carcinogenesis, and for analyzing primary cultures and assessing tumor prognosis and drug sensitivity. The assay can also be adapted to analysis of microbial colonies. | 10.1002/1097-0320(20000801)40:4<271::aid-cyto3>3.0.co;2-c |
pubmed_163_19270 | BACKGROUND
In lateral cervical disc herniations, posterior foraminotomy (PF) provides direct nerve root decompression and maintains segmental mobility. However, partial facetectomy can cause instability. This study evaluated long-term clinical outcomes related to cervical sagittal alignment after PF.
METHODS
The study included 48 consecutive patients with lateral cervical disc herniations who underwent PF. Pain and mobility were evaluated using the Numeric Rating Scale and Neck Disability Index (NDI), respectively. Sagittal alignment was evaluated using the modified Toyama method.
RESULTS
Median Numeric Rating Scale arm, Numeric Rating Scale neck, and NDI scores improved by 7, 4.5, and 24 points, respectively. Corresponding mean minimal clinically important differences were achieved in 94%, 77%, and 98% of patients at a mean follow-up of 8.4 years. Of patients, 82% showed favorable radiological results (i.e., retained or developed lordosis or had straight spine), while 18% showed unfavorable radiological results (i.e., retained or changed toward kyphosis). The latter group had multilevel cervical degenerative disc disease (mcDDD) before PF. Nevertheless, the risk of developing kyphosis was only 2.6%, and the potential for improving sagittal balance was 43%. Follow-up median NDI scores, but not minimal clinically important differences, were significantly worse in patients with preoperative kyphosis (21 vs. 8; P = 0.03) or mcDDD (20 vs. 8; P = 0.024) compared with other patients.
CONCLUSIONS
Patients with preoperative kyphosis or mcDDD had worse NDI outcomes but also benefited from PF. Sagittal alignment improved in >40% of patients, but coexisting mcDDD was a main risk factor for kyphosis persistence. | 10.1016/j.wneu.2021.11.072 |
pubmed_127_261 | The regulation by substrate induction of the acetohydroxy acid isomeroreductase was studied in Escherichia coli. Induction was inhibited by chloramphenicol and rifampin. The addition of rifampin resulted in a decay of the capacity to form isomeroreductase. This was attributed to the breakdown of the isomeroreductase messenger, which had a half-life of about 45 sec at 37 C. Induction of isomeroreductase was enhanced by including glucose in the medium. This effect was shown to be due in part to the lowering of the pH of the medium, which presumably made inducer entry more rapid. | 10.1128/jb.112.1.131-141.1972 |
pubmed_146_2017 | The purpose of immunotoxicity testing is to obtain data that is meaningful for safety assessment. Host resistance assays are the best measure of a toxicant's effect on the overall ability to mount an effective immune response and protect the host from infectious disease. An outline is presented for immunotoxicological evaluation using host resistance assays. The influenza virus host resistance model is useful to evaluate the overall health of the immune system and is one of the most thoroughly characterized host resistance models. Viral clearance requires all aspects of the immune system to work together and is the ultimate measure of the health of the immune system in this model. Mechanistic immune functions may be included while measuring viral clearance and include: cytokines, macrophage activity, natural killer (NK) cell activity, cytotoxic T-lymphocyte (CTL) activity, and influenza-specific IgM and IgG. Measurement of these immunological functions provides an evaluation of innate immunity (macrophage or NK activity), an evaluation of cell-mediated immunity (CMI) (CTL activity), and an evaluation of humoral-mediated immunity (HMI) (influenza-specific IgM or IgG). Measurement of influenza-specific IgM or IgG also provides a measurement of T-dependent antibody response (TDAR) since influenza is a T-dependent antigen. There are several targeted host resistance models that may be used to answer specific questions. Should a defect in neutrophil and/or macrophage function be suspected, Streptococcus pneumoniae, Pseudomonas aeruginosa, or Listeria monocytogenes host resistance models are useful. Anti-inflammatory pharmaceuticals or therapeutics for rheumatoid arthritis or Crohn's disease that target TNFalpha may also be evaluated for immunotoxicity using the S. pneumoniae intranasal host resistance assay. Marginal zone B (MZB) cells are required for production of antibody to T-independent antigens such as the polysaccharide capsule of the encapsulated bacteria that are so prominent in causing blood-borne infections and pneumonia. Intravenous infection with Streptococcus pneumoniae, an encapsulated bacterium, results in a blood-borne infection that requires MZB cells for clearance. The systemic S. pneumoniae host resistance assay evaluates whether a therapeutic test article exerts immunotoxicity on MZB cells and measures the T-independent antibody response (TIAR). Suppression of CMI or in some cases HMI may result in reactivation of latent virus that may result in a fatal disease such as progressive multifocal leukoencephalopathy (PML). The murine cytomegalovirus (MCMV) reactivation model may be used to evaluate a pharmaceutical agent to determine if suppression of CMI or HMI results in reactivation of latent virus. Candida albicans is another host resistance model to test potential immunotoxicity. Host resistance assays have been the ultimate measure of immunotoxicity testing for environmental chemicals and pharmaceutical small molecules. Human biologicals are now an important component of the drug development armamentarium for biotech and pharmaceutical companies. Many human biologicals are fusions of IgG, and/or target immune mediators, immunological receptors, adhesion molecules, and/or are indicated for diseases that have immune components. It is therefore necessary to thoroughly evaluate human biological therapeutics for immunotoxicity. Numerous biologicals that are pharmacologically active in rodents can be evaluated using well-characterized rodent host resistance assays. However, biologicals not active in rodents may use surrogate biologicals for testing in rodent host resistance assays, or may use host resistance assays in genetically engineered mice that mimic the effect of the human biological pharmacological agent. | 10.1080/15476910801897557 |
pubmed_156_1809 | The aim of the present study was to investigate the prevalence of c-FLIP [cellular FLICE-inhibitory protein, where FLICE is Fas-associated death domain (FADD)-like interleukin-1beta-converting enzyme] expression in gastric adenocarcinoma and its possible implications for the progression of the cancer. Expression of c-FLIP in 48 gastric adenocarcinomas and their normal counterparts was analysed by reverse transcriptase PCR, Western blotting and immunohistochemistry. In situ cell apoptosis was detected by TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling) assay. As a result, c-FLIP transcripts were constitutively expressed in gastric adenocarcinomas and their levels were significantly higher than those in matched normal tissues ( P < 0.01). Immunohistochemically, the c-FLIP protein was also found to be expressed in all gastric adenocarcinomas (48/48), and 68.8% (33/48) showed an intense immunostaining; in contrast, only 75% (36/48) of normal gastric mucosa showed positive staining and none of them immunostained intensely. The abundance of c-FLIP protein was significantly higher in carcinoma than in normal gastric mucosa (6.93 +/- 0.58 versus 3.19 +/- 0.26, P < 0.01) and showed a reverse correlation with apoptotic index in adenocarcinoma, but not in normal mucosa. In addition, abundance of c-FLIP was significantly associated with lymph node metastasis at both mRNA level ( P < 0.05) and protein level ( P < 0.01). Western-blot analysis showed that the expression levels of the long form of c-FLIP and the short form of c-FLIP in adenocarcinomas were 2.6-fold and 2.8-fold ( P < 0.01) higher than those in normal tissues respectively. However, no significant difference was found between the expression levels of the two isoforms in both adenocarcinomas or normal tissues. In conclusion, overexpression of c-FLIP is tumour specific, which may be one of the in vivo mechanisms by which tumour cells escape from apoptotic death during the malignant transformation, and plays an important role in lymph node metastasis of gastric adenocarcinoma, which ultimately contributes to the tumour progression. | 10.1042/CS20030238 |
pubmed_101_11279 | Tuberculosis (TB) is a worldwide health problem; successful interventions such as vaccines and treatment require a 2better understanding of the immune response to infection with Mycobacterium tuberculosis (Mtb). In many infectious diseases, pathogen-specific T cells that are recruited to infection sites are highly responsive and clear infection. Yet in the case of infection with Mtb, most individuals are unable to clear infection leading to either an asymptomatically controlled latent infection (the majority) or active disease (roughly 5%-10% of infections). The hallmark of Mtb infection is the recruitment of immune cells to lungs leading to development of multiple lung granulomas. Non-human primate models of TB indicate that on average <10% of T cells within granulomas are Mtb-responsive in terms of cytokine production. The reason for this reduced responsiveness is unknown and it may be at the core of why humans typically are unable to clear Mtb infection. There are a number of hypotheses as to why this reduced responsiveness may occur, including T cell exhaustion, direct downregulation of antigen presentation by Mtb within infected macrophages, the spatial organization of the granuloma itself, and/or recruitment of non-Mtb-specific T cells to lungs. We use a systems biology approach pairing data and modeling to dissect three of these hypotheses. We find that the structural organization of granulomas as well as recruitment of non-specific T cells likely contribute to reduced responsiveness. | 10.3389/fimmu.2020.613638 |
pubmed_728_5983 | In 32 beagles heterotopic renal allotransplantations and bilateral nephrectomies were carried out. Control animals (5 dogs) survived 9.4 +/- 1.6 days. 22 recipients were pretreated with donor-specific semisoluble spleen antigen; 5 recipients pretreated with the antigen alone (780 mg/kg body weight) survived 16.6 +/- 2.3 days. A pretreatment with antigen combined with 5 mg/kg body weight Prednisolone resulted in no significant prolongation of survival time (5 animals), but 5 dogs survived significantly longer after pretreatment with the antigen and 50 mg/kg body weight Prednisolone (27.4 +/- 2,7 days). In 5 recipients after preoperative application of 3 doses Prednisolone alone (50 mg/kg body weight each) no prolongation of survival time could be observed (10.2 +/- 0.7 days). We found no correlation between lymphocytotoxic antibody titre and survival time. | pubmed_728_5983 |
pubmed_315_20508 | A 5-year-old girl with a remote history of idiopathic thrombocytopenic purpura presented with a history of partial nasolacrimal duct obstruction unresolved with standard treatments of probing, irrigation, and lacrimal system intubation. Surgical exploration revealed canaliculitis with dacryolith formation within the inferior canalicular system. After punctoplasty and removal of the dacryoliths, the patient had full resolution of symptoms. Although the diagnosis is uncommon in this age group, it should be included in the differential diagnosis of chronic or recurrent pediatric nasolacrimal obstruction. | 10.1097/01.iop.0000124682.88447.3c |
pubmed_12_9167 | Guinea pigs infested with Trichinella (5-10 larvae per 1 g body weight) at the intestinal (at days 2-4 of infection), migration al (at days 6-11), and muscular (at days 22-27) stages of invasion, were given voltaren, 2.14 mg/kg daily, and mebendazole, 75 mg/kg daily. The amount of adult Trichinella in small intestine and larvae in the diaphragm, T- and B-lymphocyte count (T-REC and B-RFC), functional leukocyte activity in RTML for FGA and Trichinella larvae antigens, content of circulating immune complexes and complement were determined. Voltaren did not cause delay in adult Trichinella elimination from the intestine of experimental animals, it also did not increase invasion rate at the muscular stage. As compared to the control, T- and B-lymphocyte content and RTML for FGA remained unaltered. Experimental animals show elevated blood complement activity and RTML inhibition of trichinella antigens. The combination of mebendasole and voltaren did not reduce parasitogenic effect. Despite the terms of drug injection, T- and B-lymphocytes count and complement levels in blood were found to increase, as well as the RTML index on FGA and its inhibition of specific antigens as compared with the infected untreated animals. | pubmed_12_9167 |
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