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pubmed_282_7622 | The management of patients with metastatic renal cell carcinoma (RCC) has changed dramatically over the past few years. Nephrectomy remains an important intervention for localized RCC but systemic therapy is the mainstay of treatment for patients who relapse after surgery or who have metastatic RCC. Before 2005, medical therapies for RCC were limited to cytokine therapies, which are very toxic and benefit only a small percentage of patients. In 2017, therapeutic agents now include kinase and immune checkpoint inhibitors. Contemporary research with these agents is now focusing on combinatorial and perioperative therapy. The field is now faced with the evolving challenge of how to select the best therapy for each patient during their natural history of disease, which has created a strong interest in modern sequencing and molecular approaches to identify biomarkers to personalize treatments. New therapeutic agents and approaches are associated with different toxicities and financial burdens, which require consideration of value by measuring clinical benefit, toxicity, and the cost of each drug with an organized framework. In this Review, we discuss the mechanisms underlying RCC and how improved molecular understanding helped the development of therapies, as well as biomarkers of response to treatment. We also discuss the value of these agents and their impact on personalization of therapy and drug development for RCC. | 10.1038/nrneph.2017.82 |
pubmed_622_7813 | Wolbachia are maternally inherited bacteria that commonly spread through host populations by causing cytoplasmic incompatibility, often expressed as reduced egg hatch when uninfected females mate with infected males. Infected females are frequently less fecund as a consequence of Wolbachia infection. However, theory predicts that because of maternal transmission, these "parasites" will tend to evolve towards a more mutualistic association with their hosts. Drosophila simulans in California provided the classic case of a Wolbachia infection spreading in nature. Cytoplasmic incompatibility allowed the infection to spread through individual populations within a few years and from southern to northern California (more than 700 km) within a decade, despite reducing the fecundity of infected females by 15%-20% under laboratory conditions. Here we show that the Wolbachia in California D. simulans have changed over the last 20 y so that infected females now exhibit an average 10% fecundity advantage over uninfected females in the laboratory. Our data suggest smaller but qualitatively similar changes in relative fecundity in nature and demonstrate that fecundity-increasing Wolbachia variants are currently polymorphic in natural populations. | 10.1371/journal.pbio.0050114 |
pubmed_12_5493 | In 1987, we reported the 1-year migration of the prosthetic components in 16 hips followed by roentgen stereophotogrammetry after fixation with either low- or high-viscosity cement. We now report the migration of these prosthetic components during another 2 postoperative years. Eight acetabular components, four in each group, migrated cranially; and four femoral components, three in the low-viscosity and one in the high-viscosity group, migrated distally. All but two migrations were obvious 4 months postoperatively, which indicates that what is called late loosening is the result of late detection rather than of late occurrence of loosening. Low-viscosity cement did not provide improved prosthetic fixation. | 10.3109/17453679008993518 |
pubmed_737_11461 | A series of novel heterocyclic homotriptycenes bearing furan, thiophene, and pyridine rings, 7a-f, were synthesized by intramolecular dehydration reactions of 10,10-dihetarylmethyl-9,10-dihydroanthracen-9-ols 6a-f. In the presence of acids, the secondary alcohols 6a-f show different reactions which depend on the electron densities of the attached heterocyclic rings. The initially formed carbenium ions react in an electrophilic substitution with electron-rich heterocycles. The formation of a transannular bridge (1,7-elimination) leads to homotriptycenes in high yields. When the heterocyclic ring has a moderate electron density, two competitive reactions exist, which afford 9-monosubstituted anthracenes by 1,4-elimination or 9,10-disubstituted anthracenes by a rearrangement, respectively. Electron-deficient heterocycles undergo a disproportionation to give hydrocarbons and ketones. | 10.1021/jo200110w |
pubmed_931_2539 | Toll-like receptors (TLR) recognize not only microbial products, but also danger signals released from damaged tissues. Although we have previously shown that TLR4 is upregulated following trauma hemorrhage, the exact role of TLR4 in the posttraumatic immune response is unclear. To study this, C3H/HeOuJ (functional TLR4) or C3H/HeJ (TLR4 mutant) mice were subjected to laparotomy and hemorrhagic shock followed by resuscitation with 4x the shed blood volume in the form of Ringer's lactate. Sham operated mice underwent same surgical procedure, but neither hemorrhage nor resuscitation was performed. Four hours after resuscitation, the mice were sacrificed, plasma and lungs were collected and Kupffer cells were isolated. Plasma chemokine (MCP-1 and KC) levels, Kupffer cell chemokine production, and lung chemokine content were determined. Lung neutrophil infiltration was assessed by tissue content of myeloperoxidase. The chemokine levels in plasma, Kupffer cell supernatants and lung tissue were elevated in C3H/HeOuJ mice subjected to trauma hemorrhage compared to shams. No such changes were observed in C3H/HeJ mice undergoing trauma hemorrhage. Mice with functional TLR4 expression showed elevated lung neutrophil infiltration following trauma hemorrhage, which was not observed in TLR4 mutant mice. These findings suggest that functional TLR4 signaling is critical in mediating the inflammatory response following trauma hemorrhage. Thus, modulation of the TLR4 after injury may serve as a future therapeutic target in trauma patients. | 10.1016/j.molimm.2006.12.009 |
pubmed_585_23785 | Spinal cord injury (SCI) causes the irreversible loss of spinal cord parenchyma including astroglia, oligodendroglia and neurons. In particular, severe injuries can lead to an almost complete neural cell loss at the lesion site and structural and functional recovery might only be accomplished by appropriate cell and tissue replacement. Stem cells have the capacity to differentiate into all relevant neural cell types necessary to replace degenerated spinal cord tissue and can now be obtained from virtually any stage of development. Within the last two decades, many in vivo studies in small animal models of SCI have demonstrated that stem cell transplantation can promote morphological and, in some cases, functional recovery via various mechanisms including remyelination, axon growth and regeneration, or neuronal replacement. However, only two well-documented neural-stem-cell-based transplantation strategies have moved to phase I clinical trials to date. This review aims to provide an overview about the current status of preclinical and clinical neural stem cell transplantation and discusses future perspectives in the field. | 10.1007/s00441-012-1363-2 |
pubmed_579_4201 | STUDY OBJECTIVE
To describe the clinical characteristics and treatment of ovarian torsion in premenarchal girls with surgically verified ovarian torsion.
DESIGN AND PARTICIPANTS
A retrospective cohort study design was used. The medical charts of all premenarchal girls with surgically verified ovarian torsion treated in a university-affiliated tertiary medical center from 1997 to 2012 were reviewed for clinical, treatment, and outcome data.
RESULTS
Thirty-two premenarchal girls were identified. Their median age was 9 years. There were 7 recurrences during the study period (17.9%), for a total of 39 cases. The main presenting symptoms were abdominal pain (92.3%) and nausea and vomiting (84.6%). Physical examination revealed abdominal tenderness in 25 cases (64.1%). Abdominal ultrasound, performed in 31 patients (38 cases), yielded pathologic findings in 28 (73.7%), mainly an enlarged ovary (11 cases, 28.9%). Doppler flow studies were abnormal in 15 cases. In 26 cases (68.4%), the tentative preoperative working diagnosis was ovarian torsion. Laparoscopy was performed in 26 cases, laparotomy in 10, and laparoscopy converted to laparotomy in 3 cases. Conservative management, mainly with additional cyst drainage or cystectomy, was used in 37 cases (95.2%) with oophoropexy in 5 cases. Two patients required oophorectomy because of a suspected neoplasm and severe ovarian necrosis. Pathologic examination demonstrated 5 simple cysts, 1 necrotic ovary, and 1 mature cystic teratoma.
CONCLUSIONS
Ovarian torsion in premenarchal girls is associated with nonspecific signs and symptoms. Abdominal ultrasound and Doppler imaging may assist in the diagnosis. Laparoscopy with conservative management is preferred. Owing to the high recurrence rate, oophoropexy may be considered. | pubmed_579_4201 |
pubmed_69_18108 | The role of mutations in the melanocortin-3 receptor (MC3R) gene, which is implicated in the regulation of energy homeostasis, is still under debate. Animal studies have clearly proven that, together with the melanocortin-4 receptor (MC4R), the MC3R is a critical receptor for melanocortin peptides within the leptin-melanocortin signaling cascade. However, as several mutations have been found in lean individuals and not all mutations seem to cause receptor dysfunction, results from mutation screens in obese humans remain controversial. In the present study, we screened for rare variants in the MC3R gene of obese children and lean controls to assess the prevalence of MC3R mutations in the Belgian population. We screened 249 severely overweight and obese children and adolescents and 239 lean adults for mutations in the coding region of MC3R. Mutation screening was performed by high resolution melting curve analysis and direct sequencing. We identified four non-synonymous coding variations in the obese population, all of which had been reported previously. In addition, we also found four novel rare MC3R variants in the lean control population, suggesting that not all MC3R mutations are disease-causing. Overall, the total prevalence of rare MC3R variants was 1 % in Belgian obese children and adolescents compared to 1.02 % in lean controls. Ultimately, cosegregation studies combined with comprehensive functional analysis is required to determine the potential pathogenic role of rare MC3R variants in causing human obesity. | 10.1007/s12020-012-9862-1 |
pubmed_1100_5618 | The energy intakes, anthropometry and blood pressure of 62 expeditioners at one Australian sub-Antarctic (Macquarie Island) and two Antarctic stations (Davis and Casey) were examined over a 12 month period. High mean energy intakes were found at all stations (approximately 16,000 kJ/subject/day). Mean subject body weight tended to rise during the winter months (midway during the study) and fall during the spring, although there were no significant changes (p < 0.05) seen at any of the stations over the year. Subjects were generally leaner at the end of 12 months as evidenced by significant falls (p < 0.01) in mean sum of skinfold thickness at two stations over the year. At all stations, blood pressure trended downwards during the year, with significant rises (p < 0.01) seen at one station during the spring. Two 12-week dietary intervention periods were introduced during the year at one of the Antarctic stations to investigate the effects of low-cholesterol (< 300 mg/day), low-fat (< 30% of energy) and high-fibre (> 30 g/day) diets. The average energy intake/day during these two periods (14,973 kJ and 14,515 kJ) was slightly less than during the baseline diet (average of 16,228 kJ). This was reflected in the anthropometric measurements with the mean body weight, sum of skinfold thickness and waist/hip ratios trending down during the diet periods. The study confirms earlier reports of high mean energy intake in Antarctica and suggests that the techniques of measuring intake may have been more accurate than those used in large population studies where intake may have been under-estimated. The results indicate seasonal fluctuations in blood pressure and anthropometric parameters and demonstrate that these anthropometric parameters were affected by the balance of energy intake and activity. | pubmed_1100_5618 |
pubmed_669_25491 | Animal studies are a critical component in biomedical research, pharmaceutical product development, and regulatory submissions. There is a worldwide effort in toxicology toward "reducing, refining, and replacing" animal use. Here, we proposed a deep generative adversarial network (GAN)-based framework capable of deriving new animal results from existing animal studies without additional experiments. To prove the concept, we employed this Tox-GAN framework to generate both gene activities and expression profiles for multiple doses and treatment durations in toxicogenomics (TGx). Using the pre-existing rat liver TGx data from the Open Toxicogenomics Project-Genomics-Assisted Toxicity Evaluation System (Open TG-GATES), we generated Tox-GAN transcriptomic profiles with high similarity (0.997 ± 0.002 in intensity and 0.740 ± 0.082 in fold change) to the corresponding real gene expression profiles. Consequently, Tox-GAN showed an outstanding performance in 2 critical TGx applications, gaining a molecular understanding of underlying toxicological mechanisms and gene expression-based biomarker development. For the former, over 87% agreement in Gene Ontology was found between Tox-GAN results and real gene expression data. For the latter, the concordance of biomarkers between real and generated data was high in both predictive performance and biomarker genes. We also demonstrated that the Tox-GAN models constructed with the Open TG-GATES data were capable of generating transcriptomic profiles reported in DrugMatrix. Finally, we demonstrated potential utility for Tox-GAN in aiding chemical-based read-across. To the best of our knowledge, the proposed Tox-GAN model is novel in its ability to generate in vivo transcriptomic profiles at different treatment conditions from chemical structures. Overall, Tox-GAN holds great promise for generating high-quality toxicogenomic profiles without animal experimentation. | 10.1093/toxsci/kfab157 |
pubmed_363_8459 | Human red blood cell (RBC, erythrocyte) membranes have internal protein skeletons that govern the cells' distinctive discocyte-echinocyte morphology (shape) changes, seen in conventional microscopy. Glycophorin, the cell's transmembrane protein, presents all of its saccharides outside the cell. The protein sector of glycophorin is linked inside to the RBC cytoskeleton, enabling lectins binding to the external saccharides to gain profound control over internal cytoskeleton behavior, expressed by governance of the visibly seen cell shape. Critical lectin binding stoichiometries ((125)I-labeled lectins) equate to the number of glycophorin monomers per RBC, 7 x 10(5) copies/cell. Wheat germ agglutinin lectin (sialic acid specific) binds to glycophorin's outermost (exo) saccharides and exerts tight control over the cell's morphology. Removal of sialic acid groups (desialation) exposes the endosaccharides of glycophorin, enabling peanut agglutinin and Osage orange lectins to gain equally tight control over the RBC's morphology behavior in simple stoichiometric ratios, bound lectin molecules/glycophorin receptor. Thus, lectin specificities for saccharides are sharply in register with the glycophorin external saccharide composition, the sequence along the chains, and the number of copies of protein (stoichiometry). These relationships were determined via RBC shape change equilibria and also via shape change rates. Rate data are somewhat laborious to determine, but are exquisitely sensitive to lectin specificities and in very small lectin concentrations. Both classes of data enable these interactions to be analyzed in lectin and RBC concentrations approximately 100-fold smaller than agglutinating levels. | 10.1021/jf020261n |
pubmed_848_8673 | Twenty-five inpatients with acute exacerbations of schizophrenia (by Research Diagnostic Criteria) or schizoaffective disorder underwent a prospective haloperidol dosing procedure and were assigned fixed doses chosen to yield a distribution of haloperidol plasma levels above and below a hypothesized upper therapeutic limit of 18 ng/ml. Changes in Brief Psychiatric Rating Scale scores after 1 week of treatment were negatively correlated with haloperidol plasma levels, and the statistically optimum cutoff point fell near the predicted 18 ng/ml. Plasma level/response relationships over the subsequent 3 weeks were weaker but patients with higher plasma levels had consistently less improvement. | 10.1097/00004714-199010060-00003 |
pubmed_868_6864 | BACKGROUND AND AIMS
Because a traditional rendezvous (RV) technique implies stretching of the papilla, possibly leading to post-ERCP pancreatitis, an alternative duodenal RV technique was evaluated. The aim was to assess the effectiveness, safety, and amount of time spent performing duodenal RV versus traditional RV cannulation in orthotopic liver transplantation patients with a T-tube.
METHODS
We retrospectively reviewed data from a prospective ERCP database held by our university hospital. Twenty patients with a T-tube who had undergone ERCP for biliary adverse events after orthotopic liver transplantation were included. The successful cannulation rate, the amount of time spent performing cannulation, the post-ERCP pancreatitis rate, and hyperamylasemia 24 hours after the procedure were recorded.
RESULTS
Successful cannulation was achieved by the duodenal RV technique in 9 of 10 patients (90%), taking 146 seconds (interquartile range 63-341 seconds) with a short learning curve effect. An unsuccessful duodenal RV procedure occurred because of the angulation of the hydrophilic tip of the guidewire while crossing the papilla, thus preventing cannulation. Successful cannulation was achieved by the traditional RV technique in all cases (N = 11), including the failed duodenal RV technique, taking 374 seconds (interquartile range 320-410 seconds) (P < .05 vs duodenal RV). However, no post-ERCP pancreatitis occurred after using the duodenal RV technique compared with 2 episodes of mild pancreatitis after using the traditional RV technique. Twenty-four hours after the procedure, the median amylasemia level was 84 IU/L (interquartile range 49-105 IU/L) and 265 IU/L (interquartile range 73-2945 IU/L) for the duodenal versus traditional RV techniques, respectively (P = not significant).
CONCLUSIONS
In patients with a T-tube after liver transplantation, the duodenal RV technique was not associated with post-ERCP pancreatitis, presumably because of the reduction of stress on the major papilla. Cannulation by using the duodenal RV technique was faster compared with the traditional RV technique. These preliminary data point out the use of the duodenal RV technique as the first option to choose in case of failed cannulation before attempting the traditional RV technique. | pubmed_868_6864 |
pubmed_262_13371 | Decadal-scale observations of marine reserves suggest that indirect effects on taxa that occur through cascading trophic interactions take longer to develop than direct effects on target species. Combining and analyzing a unique set of long-term time series of ecologic data in and out of fisheries closures from disparate regions, we found that the time to initial detection of direct effects on target species (±SE) was 5.13 ± 1.9 years, whereas initial detection of indirect effects on other taxa, which were often trait mediated, took significantly longer (13.1 ± 2.0 years). Most target species showed initial direct effects, but their trajectories over time were highly variable. Many target species continued to increase, some leveled off, and others decreased. Decreases were due to natural fluctuations, fishing impacts from outside reserves, or indirect effects from target species at higher trophic levels. The average duration of stable periods for direct effects was 6.2 ± 1.2 years, even in studies of more than 15 years. For indirect effects, stable periods averaged 9.1 ± 1.6 years, although this was not significantly different from direct effects. Populations of directly targeted species were more stable in reserves than in fished areas, suggesting increased ecologic resilience. This is an important benefit of marine reserves with respect to their function as a tool for conservation and restoration. | 10.1073/pnas.0908012107 |
pubmed_887_5390 | Nearly 40% of AIDS patients develop neurological complications during the course of their illness, and about 10% experience neurological symptoms as the initial manifestations of AIDS. The most common neurological complication (14% of AIDS patients) is human immunodeficiency virus (HIV) encephalopathy, but opportunistic viral and nonviral infections and neoplasms are also quite common; the most frequent among these are cryptococcal meningitis, toxoplasmosis, primary central nervous system (CNS) lymphoma, progressive multifocal leukoencephalopathy, and herpesvirus infections. Most of the nonviral infections and neoplasms are potentially treatable. Neurological syndromes include diffuse and regional encephalopathies, myelopathy, meningitis, intraaxial cranial neuropathies, and retinopathy. About 10% of AIDS patients develop a CNS mass lesion; the chief causes of these lesions are toxoplasmosis and primary CNS lymphoma. Since the clinical profiles of the various diseases overlap to a great extent, differential diagnosis requires a thorough workup, including magnetic resonance imaging or computed tomography brain scanning, examination of the cerebrospinal fluid, and, frequently, brain biopsy. Because AIDS patients have a high incidence of multiple intracranial pathologies, the diagnostic workup may have to be repeated to identify all of the diseases present. | pubmed_887_5390 |
pubmed_665_7016 | OBJECTIVE
To compare cognitive behaviour therapy (CBT) with CBT plus medication; medication alone; and placebo in the treatment of adult obsessive-compulsive disorder (OCD).
METHOD
Forty-eight participants (43 completers) were recruited into two protocols. In the first protocol, 21 people with OCD were randomly allocated to either a standard medication (fluvoxamine) or standard placebo condition for a 5-month period. Both these groups subsequently received CBT for a further 5 months. In the second protocol, 22 people with OCD received CBT, one group was already stabilized on an antidepressant of choice; the second group was drug naïve.
RESULTS
All active treatments, but not the placebo, showed clinical improvement. There was no difference in treatment response to CBT regardless of whether participants had previously received medication or placebo.
CONCLUSION
CBT has a more specific antiobsessional effect than medication but CBT plus medication shows greatest overall clinical improvement in mood. | 10.1111/j.1600-0447.2006.00767.x |
pubmed_291_11452 | Resprouting is an important persistence strategy for woody species and represents a dominant pathway of regeneration in many plant communities, with potentially large consequences for vegetation dynamics, community composition, and species coexistence. Most of our knowledge of resprouting strategies comes from fire-prone systems, but this cannot be readily applied to other systems where disturbances are less intense. In this study we evaluated sapling responses to stem snapping for 49 moist-forest species and 36 dry-forest species from two Bolivian tropical forests. To this end we compared in a field experiment the survival and height growth of clipped and control saplings for a two-year period, and related this to the shade tolerance, carbohydrate reserves, and the morphological traits (wood density, leaf size) of the species. Nearly all saplings resprouted readily after stem damage, although dry-forest species realized, on average, a better survival and growth after stem damage compared to moist-forest species. Shade-tolerant species were better at resprouting than light-demanding species in moist forest. This resprouting ability is an important prerequisite for successful regeneration in the shaded understory, where saplings frequently suffer damage from falling debris. Survival after stem damage was, surprisingly, only modestly related to stem reserves, and much more strongly related to wood density, possibly because a high wood density enables plants to resist fungi and pathogens and to reduce stem decay. Correlations between sampling performance and functional traits were similar for the two forest types, and for phylogenetically independent contrasts and for cross-species analyses. The consistency of these results suggests that tropical forest species face similar trade-offs in different sites and converge on similar sets of solutions. A high resprouting ability, as well as investments in stem defense and storage reserves, form part of a suite of co-evolved traits that underlies the growth-survival trade-off, and contributes to light gradient partitioning and species coexistence. These links with shade tolerance are important in the moist evergreen forest, which casts a deep, more persistent shade, but tend to diminish in dry deciduous forest where light is a less limiting resource. | 10.1890/09-0862.1 |
pubmed_641_11804 | Control of initiation of transcription of the human terminal deoxynucleotidyl transferase (TdT) gene was investigated by using an in vitro transcription assay. The precise contribution of discrete basal promoter elements to transcription initiation was determined by testing deletion and substitution mutations. The primary element, contained within the region spanning -34 to -14 bp relative to the transcription start site, accounted for 80% of basal promoter activity. TdT promoter activity required the sequence ACCCT at -24 to -20 bp since a dramatic decrease in transcription initiation was observed after mutation of this sequence, whereas mutation of the adjacent sequence from -32 to -25 bp did not alter promoter activity. The secondary element contained sequences surrounding the transcription start site and had 20% of promoter activity. Deletion of both elements completely abolished transcription initiation. Initiator characteristics of the secondary element were revealed by using the in vitro assay: promoter sequences at the transcription start site were sufficient to direct accurate initiation at a single site. Mutation of the sequence GGGTG spanning the transcription start site resulted in loss of transcription initiation. Both the primary and secondary elements were nonhomologous to corresponding regions from the mouse TdT gene promoter. While the human basal promoter functioned in the absence of TATA consensus sequences or GC-rich SP1 binding sites, it was dependent on active TFIID. In contrast to other TATA-less promoters, purified TATA binding protein substituted for the TFIID complex and restored promoter activity to TFIID-inactivated nuclear extracts. | 10.1021/bi00202a023 |
pubmed_220_6452 | Acute leukemias tend to affect a younger population and are much more common in pregnant patients than chronic leukemias are. We report a case of acute lymphoblastic leukemia diagnosed during the third trimester presenting with organomegaly and thrombocytopenia. Delivery of the fetus by cesarean section was decided because of the fulminant nature of the acute leukemia within days of admission. Bone marrow biopsy revealed acute lymphocytic leukemia, French American-British L2 subtype B cell immunotype. A left ovarian mass was identified during the cesarean section which later proved to be lymphoblastic infiltration. The patient was started on induction chemotherapy consisting of vincristine, daunorubicin, prednisolone, and l-asparaginase immediately after the diagnosis. The patient died of Acinetobacter septicemia 18 days after the first admission. | 10.1111/j.1525-1438.2003.13401.x |
pubmed_652_12515 | PURPOSE
To retrospectively compare computed tomography (CT) sensitivities of large (≥3 cm) adenoma and cortical carcinoma.
METHODS
Between January 2004 and November 2012, 43 non-oncologic patients with 43 adrenal masses [31 large adenomas, and 12 carcinomas] underwent unenhanced CT, early contrast-enhanced CT, and delayed contrast-enhanced CT scans prior to adrenalectomy. Three types of region-of-interest (ROI) were used on early contrast-enhanced CT images:aROI (large ROI) covering more than half of a mass and two small ROIs fitted to the highest (high ROI) or lowest (low ROI) attenuation area. These ROIs were also placed in the same area on the other CT images. Adenoma was diagnosed if a mass measured ≤10 HU on unenhanced CT image, or if it had ≥60% absolute percentage washout (APW)or ≥40% relative percentage washout (RPW).Carcinoma was diagnosed if a mass had <60% APW and <40% RPW. CT sensitivities for large adenoma and carcinoma were compared.
RESULTS
CT sensitivities for large adenoma vs. carcinoma were 64.5% (20/31) vs. 100% (12/12) using a large ROI, 100% (31/31) vs. 50.0% (6/12) using a high ROI, and 51.6% (16/31) vs. 100% (12/12) using a low ROIs, respectively.
CONCLUSIONS
CT sensitivities for large adenoma and cortical carcinoma are influenced by the size or location of an ROI.A large ROI helps to minimize loss of CT sensitivity for large adenoma and to detect carcinoma. | 10.1007/s00261-014-0202-1 |
pubmed_57_8494 | Substance P (SP) is well known for its immunoregulatory influence on NK cells. The biological actions of SP are mediated primarily through the high-affinity neurokinin-1 receptor (NK-1R), a G protein-coupled receptor (GPCR). Receptor binding triggers a cAMP signaling pathway and intracellular levels of cAMP are regulated via Gαs and Gαi. In this study NF449, a Gαs-selective G protein antagonist, was used to study the role of Gαs in the activation of NK92-MI cells by SP. Results show that 10(-12)M SP enhances the expression of Gαs and Gαi3 in NK92-MI cells promoting a cytotoxic phenotype characterized by expression of perforin and granzyme B. Development of a cytotoxic phenotype in NK92-MI cells stimulated with SP is blunted by inhibition of Gαs by NF449. In summary, SP signaling through NK-1R promotes a cytotoxic phenotype in NK92-MI cells characterized by upregulation of both Gαs and Gαi3. NF449 inhibits Gαs, blunts SP-induced expression of perforin and granzyme B, and represents a potential therapeutic avenue for reducing NK-cell mediated cytotoxicity. | pubmed_57_8494 |
pubmed_263_1319 | OBJECTIVES
To determine the quality of life of patients with Crohn's disease and to determine if this is reflected by the quality of nursing care.
METHODS
For the purpose of this research, we used a generic standardized questionnaire of the quality of life, published by the World Health Organization (WHOQOL-100). The questionnaire was distributed among 100 patients with Crohn's disease and among 1456 and members of healthy population. To analyze the results, we used the SPSS program and appropriate statistical methods.
RESULTS
The comparison of the domain scores of population standards in the Czech Republic and the respondents with Crohn's disease revealed a difference in the domain "physical condition", where the mean value was at the limit of the lower interval of the standard, and in the domain of "independence".
CONCLUSION
The results given in this study define the possibilities of nurses and their functioning associated with altered quality of life. An evaluation of the most affected areas allows nurses to determine an appropriate intervention. Providing nursing care, in accordance with the latest knowledge, must be based on the quality of life. This newly incorporated area offers healthcare professionals a new dimension for assessing and determining subsequent interventions. | pubmed_263_1319 |
pubmed_417_16420 | Mother-infant pairs were assessed during postpartum for maternal role and identity and a variety of infant and sociodemographic characteristics. When children were school age (8 to 10 years), 77 of the original 124 mothers returned a mail survey that assessed children's social competence and behavioral problems. After controlling for socioeconomic status, neither perceived nor demonstrated role attainment predicted child outcomes. Only a subset of the maternal identity indicators predicted children's social competence and behavior problems at 9 years, and these relationships were few and modest in magnitude. Overall, little support was found for the long-term predictive power of maternal role indicators measured during postpartum. | pubmed_417_16420 |
pubmed_949_3649 | Gastrointestinal bleeding due to jejunal diverticulosis is an uncommon emergency condition that has been encountered recently in one patient. The case of this patient treated with an emergency laparotomy and a segmentary small bowel resection is here presented. The clinical significance, proper diagnostic evaluation, and treatment of the hemorrhagic complication of jejunal diverticular disease are reviewed. | pubmed_949_3649 |
pubmed_218_15007 | Ethane sulfonic acide hydrazide (esh: CH(3)CH(2)SO(2)NHNH(2)) derivatives as 5-methylsalicyl-aldehydeethanesulfonylhydrazone (5msalesh), 5-methyl-2-hydroxyacetophenoneethane sulfonylhydrazone (5mafesh) and their Ni(II), Co(II) complexes have been synthesized for the first time. The structure of these compounds has been investigated by elemental analysis, FT-IR, (1)H NMR, (13)C NMR, LC/MS, UV-vis spectrophotometric method, magnetic susceptibility, thermal studies and conductivity measurements. The antibacterial activities of synthesized compounds were studied against Gram positive bacteria; Staphylococcus aureus, Bacillus subtilis, Bacillus magaterium and Gram negative bacteria; Salmonella enteritidis, Escherichia coli by using the microdilution broth method. The biological activity screening showed that ligands have more activity than complexes against the tested bacteria. The inhibition activities of these compounds on carbonic anhydrase II (CA II) have been investigated by comparing IC(50) and K(i) values and it has been found that 5msalesh and its complexes have more enzyme inhibition efficiency than other compounds. | 10.1016/j.saa.2009.09.052 |
pubmed_681_780 | Familial cylindromatosis is an autosomal dominant predisposition to tumours of skin appendages called cylindromas. Familial cylindromatosis is caused by mutations in a gene encoding the CYLD protein of previously unknown function. Here we show that CYLD is a deubiquitinating enzyme that negatively regulates activation of the transcription factor NF-kappaB by specific tumour-necrosis factor receptors (TNFRs). Loss of the deubiquitinating activity of CYLD correlates with tumorigenesis. CYLD inhibits activation of NF-kappaB by the TNFR family members CD40, XEDAR and EDAR in a manner that depends on the deubiquitinating activity of CYLD. Downregulation of CYLD by RNA-mediated interference augments both basal and CD40-mediated activation of NF-kappaB. The inhibition of NF-kappaB activation by CYLD is mediated, at least in part, by the deubiquitination and inactivation of TNFR-associated factor 2 (TRAF2) and, to a lesser extent, TRAF6. These results indicate that CYLD is a negative regulator of the cytokine-mediated activation of NF-kappaB that is required for appropriate cellular homeostasis of skin appendages. | 10.1038/nature01803 |
pubmed_997_18854 | In this work, we investigate the capability of known quantum computing algorithms for fault-tolerant quantum computing to simulate the laser-driven electron dynamics of excitation and ionization processes in small molecules such as lithium hydride, which can be benchmarked against the most accurate time-dependent full configuration interaction (TD-FCI) calculations. The conventional TD-FCI wave packet propagation is reproduced using the Jordan-Wigner transformation for wave function and operators and the Trotter product formula for expressing the propagator. In addition, the time-dependent dipole moment, as an example of a time-dependent expectation value, is calculated using the Hadamard test. To include non-Hermitian operators in the ionization dynamics, a similar approach to the quantum imaginary time evolution (QITE) algorithm is employed to translate the propagator, including a complex absorption potential, into quantum gates. The computations are executed on a quantum computer simulator. By construction, all quantum computer algorithms, except for the QITE algorithm used only for ionization but not for excitation dynamics, would scale polynomially on a quantum computer with fully entangled qubits. In contrast, TD-FCI scales exponentially. Hence, quantum computation holds promises for substantial progress in the understanding of electron dynamics of excitation processes in increasingly large molecular systems, as has already been witnessed in electronic structure theory. | 10.1021/acs.jctc.2c00878 |
pubmed_539_15120 | For a fermion gas with equally spaced energy levels that is subjected to a magnetic field, the particle density is calculated. The derivation is based on the path integral approach for identical particles, in combination with the inversion techniques for the generating function of the static response functions. Explicit results are presented for the ground state density as a function of the magnetic field with a number of particles ranging from 1 to 45. | 10.1103/PhysRevE.63.016111 |
pubmed_702_13442 | Osteoporosis treatment aims to prevent fractures and maintain the QOL of the elderly. However, persons at high risk of future fracture cannot be effectively identified on the basis of bone density (BMD) alone, although BMD is used as an diagnostic criterion. Therefore, the WHO recommended that absolute risk for fracture (10-year probability of fracture) for each individual be evaluated and used as an index for intervention threshold. The 10-year probability of fracture is calculated based on age, sex, BMD at the femoral neck (body mass index if BMD is not available), history of previous fractures, parental hip fracture history, smoking, steroid use, rheumatoid arthritis, secondary osteoporosis and alcohol consumption. The WHO has just announced the development of a calculation tool (FRAX: WHO Fracture Risk Assessment Tool) in February this year. Fractures could be prevented more effectively if, based on each country's medical circumstances, an absolute risk value for fracture to determine when to start medical treatment is established and persons at high risk of fracture are identified and treated accordingly. | 10.3143/geriatrics.46.128 |
pubmed_881_3746 | Development of a broad based cellular and humoral immune response to hepatitis C virus (HCV) structural proteins may be important for irradication of infection. DNA-based immunization is a promising approach to generate HCV-specific immune responses. Previous studies of DNA-based immunizations in mice using an HCV core DNA expression plasmid (pHCV2-2) demonstrated an efficient CTL response against HCV core epitopes; however, the humoral and Th cell proliferative responses were found to be weak. To enhance the immunogenicity of this nonsecreted viral structural protein at the B and T cell level, we coimmunized mice with pHCV2-2 and DNA expression constructs encoding for mouse IL-2, IL-4, and granulocyte-macrophage CSF proteins. Under these experimental conditions, a seroconversion frequency to anti-HCV core increased from 40 to 80% in immunized mice. The CD4+ inflammatory T cell proliferative responses as well as CD8+ CTL activity to HCV core protein were enhanced substantially after coimmunization with the IL-2 and granulocyte-macrophage CSF DNA expression constructs. In contrast, coimmunization with an IL-4-producing construct induced differentiation of Th cells toward a Th0 subtype and suppressed HCV core-specific CTL activity. Taken together, these studies emphasize that generation of antiviral immune responses using DNA-based immunization may be modified by local cytokine production at the site of Ag presentation. | pubmed_881_3746 |
pubmed_584_23856 | A retrospective analysis of intraperitoneal mitoxantrone instillation therapy for malignant ascites in advanced breast and gynecologic pelvic cancers was performed to confirm the efficacy and safety of this therapy. Several smaller phase II trials had suggested good palliative effects. In 143 patients (37 breast cancer and 106 gynecologic cancers), 257 instillations were registered. Response in breast cancer was induced in 49% and in 63% with gynecologic cancer. Severe or life-threatening clinical or laboratory side effects related to intraperitoneal mitoxantrone occurred in 2.7% (clinical) or 1.9% (laboratory) of the 257 instillations. Induction of adverse side effect was dose dependent. Intraperitoneal chemotherapy with mitoxantrone for treatment of malignant ascites in breast cancer and gynecologic malignancy is effective and well tolerated. For this treatment 30 mg mitoxantrone in > or = 1000 mL carrier solution (e.g., saline) is recommended. A minimal concentration of at least 10 micrograms/mL should be achieved. | 10.1016/s1055-3207(03)00050-4 |
pubmed_240_11715 | BACKGROUND
Recent data about hepatitis A virus (HAV) seroprevalence in industrialized countries and the impact of travels to endemic areas are sparse or absent, particularly for children.
OBJECTIVE
To determine the impact of travel to endemic areas on HAV seroprevalence and estimate the overall HAV seroprevalence in children in France. To identify risk factors for positive HAV serologic results.
STUDY DESIGN
This prospective multicentre cross-sectional seroprevalence study took place in eight paediatric emergency units throughout France. Children 1-16 years of age following all inclusion and exclusion criteria were included. Demographic, socioeconomic, and travel data were prospectively collected with a standardized questionnaire before measurement of specific HAV antibodies. HAV seroprevalence was determined and its association with diverse variables assessed by univariate and multivariate analyses.
RESULTS
430 children were included, of whom 116 had travelled to endemic areas. The HAV seroprevalence in the overall population was 5% (95%CI, 3-7) and was higher among the travellers (12% [95%CI, 6-18]) than among the others (2% [95%CI, 0-3]), OR=7.0 [95%CI, 2.6-18.8]. Risk factors identified for positive serologic results for HAV were travel to an endemic area >7 days (adjusted OR [aOR]=4.3 [95%CI, 1.5-12]), age of 14-16 years (aOR=7.7 [95%CI, 1.6-38.3]) and mother's birth in an endemic area (aOR=5.2 [95%CI, 1.8-14.8]).
CONCLUSION
Statistical evidence showed that travel to endemic areas and parents' place of birth both play a role in HAV serologic results in children with a significant difference of HAV seroprevalence between traveller and non-traveller children in France. | pubmed_240_11715 |
pubmed_64_8110 | This work aims to describe the technique and review all transvaginal natural orifice transluminal endoscopic surgery (vNOTES) for adnexal procedures performed and to acknowledge vNOTES as an alternative to conventional laparoscopy. The procedure consisted of an incision in the Pouch of Douglas, insertion of a single port device, laparoscopic surgery through the device, extraction of specimens through the vagina and closure of the vaginal apex with a direct suture. Eighteen procedures have been successfully completed, 1 patient required conversion to conventional abdominal surgery due to intolerance to pneumoperitoneum. Surgeries' length range was 45-210 minutes. The estimated blood loss was less than 100 mL. The patients required minimal analgesia, were discharged the day after and had no postoperative complications. No patients complained of dyspareunia. Two patients conceived after surgery. vNOTES is a safe and desirable approach to the adnexa and a reasonable alternative to conventional laparoscopy or vaginal surgery.Impact statementWhat is already known on this subject? Natural Orifice Transluminal Surgery (NOTES) is a technique used to access the abdominal cavity through natural orifice. Compared to conventional laparoscopy, it's expected to have fewer complications.What do the results of this study add? This is one of the few works addressing vNOTES adnexal surgery, which appears to be a good alternative to conventional laparoscopy.What are the implications of these findings for clinical practice and/or further research? vNOTES may be a desirable approach to the adnexa. This work opens a door to new research regarding vNOTES in more complex gynaecologic procedures. | 10.1080/01443615.2020.1841124 |
pubmed_1027_17089 | As a part of a program to develop starter cultures aiding in the spoilage control and sanitation of African fermented foods, a cereal-based food ('ogi' and its solid form 'agidi' or 'eko') was prepared using a bacteriocin-producing Lactobacillus strain as the starter culture. The survival of an enterotoxigenic Escherichia coli strain was investigated in the naturally fermented food and in food fermented with the starter bacteriocin-producing Lactobacillus strain. An inhibition of E. coli was observed within 2 h of incubation in 'ogi' fermented with the bacteriocin producing strain. After 6 h, the viable count of E. coli in locally fermented 'ogi' was log 6.41 (2.54 X 10(6) CFU/mL), whereas in 'ogi' fermented with the bacteriocin producer it was reduced to log 1.70 (0.5 x 10(2) CFU/mL). Comparison of the shelf life of 'agidi' prepared from the naturally fermented food with that bacteriocin-producing starter culture showed that the latter had a better shelf life (kept for 11 d before spoilage occurred as compared with 7 d for the natural one). The results are discussed in terms of the potential of bacteriocin-producing cultures in the control and retardation of spoilage and food-forne infections in some African fermented foods. | 10.1007/BF02898642 |
pubmed_452_13094 | Environmental and occupational exposure to heavy metals, including cadmium (Cd), is associated with extremely adverse impacts to living systems. Antioxidant agents are suggested to eliminate Cd intoxication. In this paper, we investigated the potential neuroprotective effect of protocatechuic acid (PCA) against Cd-induced neuronal damage in rats. Adult male Wistar rats were randomly divided into control, PCA (100 mg/kg)-treated, CdCl2 (6.5 mg/kg)-treated, and PCA and Cd treatment groups. Pre-treatment with PCA significantly reduced Cd concentrations and increased cortical acetylcholinesterase activity and brain derived neurotrophic factor. Additionally, PCA also prevented CdCl2-induced oxidative stress in the cortical tissue by preventing lipid peroxidation and the formation of nitric oxide (NO), and significantly enhancing antioxidant enzymes. Molecularly, PCA significantly up-regulated the antioxidant gene expression (Sod2, Cat, Gpx1, and Gsr) that was down-regulated by Cd. It should be noted that this effect was achieved by targeting the nuclear-related factor 2 (Nfe2l2) mRNA expression. PCA also prevented the Cd-induced inflammation by reducing the pro-inflammatory cytokines, including tumor necrosis factor-α and interleukin-1β. Moreover, PCA supplementation relieved the Cd-induced neuronal death by increasing Bcl-2 and decreasing Bax and Cas-3 levels in the cortical tissue. The improvement of the cortical tissue histopathology by PCA confirmed the biochemical and molecular data. Collectively, our findings indicate that PCA can counteract Cd-induced cortical toxicity by enhancing the antioxidant defense system and suppressing inflammation and apoptosis. | 10.1016/j.scitotenv.2020.137969 |
pubmed_441_12204 | The response of intramuscularly growing KHT sarcomas to the chemotherapeutic agent (1-(2-cloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) alone or simultaneously with the chemical radio-sensitizer misonidazole (MISO) was assessed using either a tumour growth-delay assay or an in vivo-in vitro tumour-excision assay. Median tumour growth delay following the combination of 20 mg/kg CCNU and either 0.5 or 1.0 mg/g MISO was 19.5 and 21.5 days, compared to 10 days for this CCNU dose alone. A similar degree of enhanced tumour response by MISO (factor of approximately 2 in tumour growth delay) was seen in RIF-1 tumours treated with 20 mg/kg CCNU plus 1.0 mg/g MISO. Clonogenic cell-survival studies with KHT sarcomas demonstrated that MISO at doses of 0.25, 0.5 or 1.0 mg/g given simultaneously with a range of CCNU doses produced dose-modifying factors (DMFs) of 1.9, 2.1 and 2.4 respectively. Normal tissue toxicity assessed by an LD50/7 assay led to DMFs of 1.2 and 1.4 for CCNU doses combined with 0.5 and 1.0 mg/g MISO. Thus in this animal tumour model the combination of CCNU and MISO appears to lead to a potential gain by a factor of approximately 1.7. | 10.1038/bjc.1981.57 |
pubmed_1021_22770 | Uranostaphyloplasty method is suggested for cases with unilateral total palatal clefts. It consists in closure of the hard palate defect without cutting mucoperiosteal grafts in it, soft palate defect closure by effective retro-transposition of the corner flaps cut out at the border between the hard and soft palate. | pubmed_1021_22770 |
pubmed_471_8579 | To determine whether a correlation exists between sugar-sweetened beverage consumption (SSB) and school free and reduced lunch (FRL) eligibility as a measure of socioeconomic status (SES). In January 2016, a modified version of the Bev 15 survey was anonymously administered to 5th and 6th grade students in 14 Chicago suburban public elementary schools. Students were asked to recall and record their beverage intake over the last 24 h for five predefined beverage groups [SSB, real fruit juice (RFJ), diet or sugar free beverages, milk, and water]. Concurrently, data regarding FRL eligibility for each of the 14 schools was obtained from the Illinois State Board of Education website. Mean student consumption of the five beverage categories in each school was correlated with the school's respective FRL status. A total of 1389 student surveys were used for analysis. FRL eligibility ranged from 16 to 64% in the 14 schools. There was a significant correlation between school FRL eligibility and consumption of SSB (p = 0.001), RFJ (p = 0.004) and diet or sugar-free beverage (p = 0.04). There was no significant correlation between FRL eligibility and consumption of water (p = 0.5), and milk (p = 0.2). This study shows that consumption of SSB highly correlates with school FRL eligibility, which can be a measure of SES. These findings reinforce the idea that there is a link between lower SES and unhealthy behaviors pertaining to dietary choices. Knowing this relationship between SSB consumption and FRL eligibility, specific schools can be targeted to reduce SSB consumption and its negative health consequences. | 10.1007/s10900-018-0588-8 |
pubmed_359_8703 | PURPOSE OF REVIEW
The success of an antihypertensive treatment is difficult to estimate by the extent of blood pressure reduction alone. Above and beyond blood pressure values in an individual patient, it is necessary to monitor the impact of antihypertensive treatment on the development or regression of hypertension-induced early end-organ damage. The intermediate objectives or surrogate endpoints may provide additional valuable information about the level of success of a given therapy in a particular patient. Moreover, monitoring intermediate objectives may provide scientific evidence for delineating the best antihypertensive treatment.
RECENT FINDINGS
The importance of assessing left ventricular mass, microalbuminuria, carotid wall thickness and the development of new-onset diabetes during antihypertensive treatment has been stressed. Left ventricular hypertrophy during antihypertensive therapy is associated with a lower likelihood of cardiovascular morbidity and mortality, independent of blood pressure lowering and treatment modalities in people with essential hypertension. Likewise, a reduction in urinary albumin excretion seems to be followed by a reduction in cardiovascular morbidity and mortality. Risk implications of reducing carotid wall thickness or of developing new-onset diabetes have been more controversial, although it seems to be that both can have a desirable effect.
SUMMARY
The available findings support the necessity to monitor intermediate objectives, aside from blood pressure measurement, during the follow-up of hypertensives. | 10.1097/01.mnh.0000168935.95527.0a |
pubmed_94_2292 | Reliable monitoring of metabolites in biofluids is critical for diagnosis, treatment, and long-term management of various diseases. Although widely used, existing enzymatic metabolite assays face challenges in clinical practice primarily due to the susceptibility of enzyme activity to external conditions and the low sensitivity of sensing strategies. Inspired by the micro/nanoscale confined catalytic environment in living cells, the coencapsulation of oxidoreductase and metal nanoparticles within the nanopores of macroporous silica foams to fabricate all-in-one bio-nanoreactors is reported herein for use in surface-enhanced Raman scattering (SERS)-based metabolic assays. The enhancement of catalytical activity and stability of enzyme against high temperatures, long-time storage or proteolytic agents are demonstrated. The nanoreactors recognize and catalyze oxidation of the metabolite, and provide ratiometric SERS response in the presence of the enzymatic by-product H2O2, enabling sensitive metabolite quantification in a "sample in and answer out" manner. The nanoreactor makes any oxidoreductase-responsible metabolite a candidate for quantitative SERS sensing, as shown for glucose and lactate. Glucose levels of patients with bacterial infection are accurately analyzed with only 20 µL of cerebrospinal fluids, indicating the potential application of the nanoreactor in vitro clinical testing. | 10.1002/advs.201903730 |
pubmed_2_15714 | BACKGROUND
The mitotic index is important in the assessment of tumors such as leiomyoma (LM) and leiomyosarcoma (LMS), which may exhibit a range of cytological atypia. The mitotic marker phosphohistone-H3 (PHH3) was shown to improve interobserver and intraobserver variability in many tumors.
MATERIALS AND METHODS
We evaluated the mitotic index in 20 pilar LM and cutaneous LMS using PHH3 and hematoxylin and eosin (H&E)-stained sections. Ki-67 staining characteristics of the tumors were also assessed.
RESULTS
Mitotic figures were more easily identified within PHH3 sections. The mitotic index per 10 high power fields (HPF) on the PHH3 stain was slightly higher than H&E both in the LM (mean 0.1, range 0-1 vs. mean 0) and LMS groups (mean 8.6 vs. 8.0 with range of 1-24 for both stains). The difference in mitotic index between the two stains was not statistically significant in either group (p = 0.7). The Ki-67 proliferative index showed a statistically significant correlation with a diagnosis of LMS.
CONCLUSION
PHH3 immunostain can simplify counting of mitotic figures in cutaneous smooth muscle neoplasms, especially those with many pyknotic nuclei, and may help to reduce interobserver variability. Ki-67 staining may also be of help in establishing a diagnosis of LMS. | 10.1111/cup.12127 |
pubmed_197_2142 | Extract: Cancer cells are able to escape immune detection and/or rejection by a variety of measures. Cell surface molecules, which are required for the effective policing of tissues by the immune system, are often modified, reduced or eliminated. In addition cancer cells secrete soluble molecules that inhibit the patients' ability to develop an immune response. The ability of the immune system to recognize and reject cancerous growths has been demonstrated in a series of experimental model systems. Efforts are now being made to use this knowledge for the treatment of cancer. Described below are two different gene-based approaches to stimulate the rejection of an established cancer in patients. The first involves procedures which modify the tumor itself, render it a more attractive target to the immune system, and allow immune cells to penetrate the tumor and kill the cancerous cells. The second approach requires a very powerful vaccine to stimulate a strong immune response against the tumor associated antigens in patients with an established cancer. Early efforts to harness the power of the immune system to eliminate cancer were made by Dr. William Coley very early in the 20th century. Dr. Coley injected cancerous tissue, usually sarcomas (tumors of the supportive tissues such as bone, cartilage fat or muscle), with a mix of bacteria and/or their toxins. This would result in an inflammatory response in the tumor and the influx of many immune cells. | pubmed_197_2142 |
pubmed_857_21499 | Traditionally malaria epidemiology has focused on factors such as parasite rates and vector dynamics without specific reference to disease. There are limited comprehensive data on malaria as a life-threatening event in African children. We have identified, through hospital surveillance, 581 episodes of severe malaria in residents of a defined area on the Kenya coast over a period of 3 years. This represents an absolute minimum risk of developing severe malaria by the fifth birthday of 1 in 15. The presentation of severe malaria showed marked seasonality, but the timing and magnitude of these fluctuations varied considerably between years. A satellite navigational system was used to define the exact location of the home of each severe malaria case. Space-time clustering of severe malaria was evident in this community. Seasonal peaks in incidence of severe malaria may comprise discrete mini-epidemics. In contrast, parasite rates in the community varied little during the course of the surveillance. The monitoring of disease, as opposed to parasitization, in children may result in more effective targeting of intervention resources. | 10.1016/0035-9203(93)90007-d |
pubmed_419_10074 | OBJECTIVE
Sleep loss negatively affects brain function with repercussion not only on objective measures of performance but also on many subjective dimensions, including effort perceived for the completion of cognitive processes. This may be particularly important in aging, which is accompanied by important changes in sleep and wakefulness regulation. We aimed to determine whether subjectively perceived effort covaried with cognitive performance in healthy late-middle-aged individuals.
METHOD
We assessed effort and performance to cognitive tasks in 99 healthy adults (66 women; 50-70 years) during a 20-hr wake extension protocol, following 7 days of regular sleep and wake times and a baseline night of sleep in the laboratory. We further explored links with cortical excitability using transcranial magnetic stimulation coupled to electroencephalography.
RESULTS
Perceived effort increased during wake extension and was highly correlated to subjective metrics of sleepiness, fatigue, and motivation, but not to variations in cortical excitability. Moreover, effort increase was associated with decreased performance to some cognitive tasks (psychomotor vigilance and two-back working memory task). Importantly, effort variations during wakefulness extension decreased from age 50 to 70 years, while more effort is associated with worse performance in older individuals.
CONCLUSION
In healthy late-middle-aged individuals, more effort is perceived to perform cognitive tasks, but it is not sufficient to overcome the performance decline brought by lack of sleep. Entry in the seventh decade may stand as a turning point in the daily variations of perceived effort and its link with cognition. (PsycInfo Database Record (c) 2022 APA, all rights reserved). | 10.1037/neu0000868 |
pubmed_281_26134 | Advanced research on improving the performance of conductive polymer composites is essential to exploring their potential in various applications. Thus, in this study, the electrical conductivity of multilayer nanofibre membranes composed of polyvinyl alcohol (PVA) with different electroconductive fillers content including zinc oxide (ZnO), multiwalled carbon nanotubes (MWNTs), and Ferro ferric oxide (Fe3O4), were produced via electrospinning. The tensile property and electrical conductivity of monolayer membranes were explored. The results showed that PVA with 2 wt.% MWNTs nanofibre membrane has the best conductivity (1.0 × 10-5 S/cm) and tensile strength (29.36 MPa) compared with other fillers. Meanwhile, the combination of multilayer membrane ZnO/Fe3O4/Fe3O4/MWNTs/ZnO showed the highest conductivity (1.39 × 10-5 S/cm). The parallel circuit and calculation of parallel resistance were attempted to demonstrate the conductive mechanism of multilayer membranes, which can predict the conductivity of other multilayer films. The production of multilayer composites that enhance electrical conductivity and improve conductive predictions was successfully explored. | 10.3390/polym14225048 |
pubmed_723_3924 | INTRODUCTION
Distinguishing between the active and inactive stages of Graves' ophthalmopathy (GO) is essential for making treatment decisions. 99mTc-DTPA SPECT/CT is sensitive in identifying inflammation in extraocular muscles of GO patients, which we designate 99mTc-DTPA-active. This study aimed to evaluate the response of 99mTc-DTPA-active GO patients to local immunosuppressive therapy.
MATERIALS AND METHODS
Sixty-four 99mTc-DTPA-active GO patients (89 eyes) were retrospectively analyzed. Forty-five patients (64 eyes) received repeated peribulbar triamcinolone injection, and 19 patients (25 eyes) received no immunosuppressive treatment. Ophthalmological assessment, including clinical activity score, eyelid retraction, eyelid aperture, proptosis, diplopia, and ocular mobility, was recorded before and after treatment.
RESULTS
Compared with untreated patients, the clinical activity score decreased significantly (P < 0.001) while eye symptoms (soft-tissue swelling and eyelid retraction and aperture) improved significantly (P = 0.02, P < 0.001, P < 0.001, respectively) in treated patients after six months. The inferior and medial recti were significantly smaller (P < 0.001, P < 0.001, respectively), and 99mTc-DTPA uptake in the two recti was significantly less (P = 0.001, P = 0.01, respectively) in treated patients than in untreated patients after 3 months.
CONCLUSION
Clinical activity score of < 3 does not indicate inactive GO, as revealed with 99mTc-DTPA SPECT/CT. Patients with 99mTc-DTPA-active GO can improve the symptoms with peribulbar triamcinolone injection. | 10.1007/s10792-019-01213-6 |
pubmed_787_13905 | BACKGROUND AND OBJECTIVES
The prevalence of obesity and diabetes mellitus continues to rise in industrialized countries. The impact of diabetes on the practice of peripheral nerve block anesthesia, however, has not been fully elucidated. The authors retrospectively evaluated the influence of diabetes, body mass index (BMI), age, and sex on the success of supraclavicular block (SCB) placed with a landmark-based paresthesia technique.
METHODS
The anesthetic records of 1858 consecutive patients who received an SCB were analyzed. Block success was documented solely on the day of surgery, without additional follow-up. Patients were categorized as diabetic (group D, n = 262) or nondiabetic (group ND, n = 1596). Block "success rate" (ie, general anesthesia not required to produce surgical conditions) was analyzed using multiple regression (multivariable linear and logistic) to assess the associations of diabetes and/or body mass index on successful surgical anesthesia.
RESULTS
Patients in group D were more likely (odds ratio, 3.3) to have a "successful" SCB for surgical anesthesia than were patients in group ND (P < 0.0001). Body mass index, age, and sex were not associated predictors of SCB "success."
CONCLUSIONS
We speculate that the "higher success" of SCB in patients with diabetes may be explained by: (i) higher sensitivity of diabetic nerve fibers to local anesthetics, (ii) possible unknown intraneural penetration before injection, and/or (iii) preexisting neuropathy with accompanying decreased sensation. In the absence of additional follow-up on these patients, these data should generate outcomes research addressing dose-response curves for patients with diabetes or at risk for diabetes. | 10.1097/AAP.0b013e3181ada58d |
pubmed_467_25828 | Primary pulmonary meningioma is extremely rare and only <45 cases have been reported since its first report by Kemnitz and Heinrich (Meningioma of lung: first report with light and electronmicroscopic findings. Ultrastruct. Pathol. 1982;3:359-65). Among these cases, only five cases were malignant or atypical. A 67-year-old female with primary pulmonary meningioma underwent thoracoscopic pulmonary wedge resection of the left lower lobe a year before. She had been aware of left thigh pain for 9 months, then she was referred to our division. Positron emission tomography-computed tomography suspected multiple bone metastasis including frontal bone, mandible, left scapula, rib, vertebra, pubis, left femur and sternum. We performed a needle biopsy of the sternum. Histopathological diagnosis was metastasis of primary pulmonary meningioma, World Health Organization grade III. We treated her with denosumab and radiation therapy targeting the left femur. Two months after the treatment, the pain had decreased and she could walk with no cane. No case of malignant extracranial meningioma with bone metastasis have been reported. | 10.1093/omcr/omaa005 |
pubmed_1132_4611 | The majority of lung cancers (LC) belong to the non-small cell lung carcinoma (NSCLC) type. The two main NSCLC sub-types, namely adenocarcinoma (AC) and squamous cell carcinoma (SCC), respond differently to therapy. Whereas the link between cigarette smoke and lung cancer risk is well established, the relevance of non-canonical Wnt pathway up-regulation detected in SCC remains poorly understood. The present study was undertaken to investigate further the molecular events in canonical and non-canonical Wnt signalling during SCC development. A total of 20 SCC and AC samples with matched non-cancerous controls were obtained after surgery. TaqMan array analysis confirmed up-regulation of non-canonical Wnt5a and Wnt11 and identified down-regulation of canonical Wnt signalling in SCC samples. The molecular changes were tested in primary small airway epithelial cells (SAEC) and various lung cancer cell lines (e.g. A549, H157, etc). Our studies identified Wnt11 and Wnt5a as regulators of cadherin expression and potentiated relocation of β-catenin to the nucleus as an important step in decreased cellular adhesion. The presented data identifies additional details in the regulation of SCC that can aid identification of therapeutic drug targets in the future. | 10.1371/journal.pone.0057393 |
pubmed_387_2495 | Five cases of neonatal cerebral venous thrombosis (NCVT) diagnosed by magnetic resonance imaging (MRI) are presented in this report. MRI was specific for the anatomic diagnosis, demonstrating involvement of the superior sagittal sinus in 3 infants or deep venous system in the remaining 2. Four cases were associated with perinatal hypoxia or cranial trauma. Three of these children show significant developmental delays. The increased use of MRI may add significant information on the association of cerebral venous thrombosis with the common systemic illnesses of newborns. | 10.1159/000120385 |
pubmed_651_14003 | The neuritic uptake and transport of three antiviral drugs were studied in a cell culture system with dissociated cells of rat dorsal root ganglia. Cultured sensory neurons extended neuritic projections which penetrated a vacuum grease sealed diffusion barrier in the culture. The peripheral infection with herpes simplex virus (HSV) type 1 (McIntyre) resulted in uptake and transport of HSV by neuritic extensions causing a neuronal infection inside the diffusion barrier. By varying the route of administration and concentration of drug and by manipulating the nerve cell culture system, neuritic uptake and transport also of the antiviral drugs (acyclovir, adenine-arabinoside and foscarnet) were demonstrable. The findings are discussed in relation to axonal transport and antiviral treatment of HSV infections of the nervous system. | 10.1007/BF01309994 |
pubmed_163_6932 | PURPOSE OF REVIEW
With increased understanding of the biomechanical function of the acetabular labrum, more attention has been directed towards surgical techniques that preserve or restore normal joint anatomy. While labral repair has been shown to produce superior outcomes to labral debridement, repair is not always possible in the setting of severe labral intrasubstance tearing or deficiency. These patients were previously left without suitable arthroscopic treatment options.
RECENT FINDINGS
Labral reconstruction is an emerging procedure that has been shown to offer promising outcomes for traditionally difficult-to-treat hip pathology. Short- and mid-term follow-up studies have consistently demonstrated significant improvement in patient-reported outcomes, function, and patient satisfaction postoperatively, often despite less favorable preoperative characteristics. Labral reconstruction is a viable arthroscopic treatment option that has been shown to reliably produce clinically meaningful results in patients with severe labral pathology that is not amenable to repair/refixation or augmentation. | 10.1007/s12178-021-09733-4 |
pubmed_151_21669 | Flies are the main competitors of dung beetles for oviposition sites and rolling dung beetles relocate their food to reduce interspecific competition. Furthermore, dung beetles deposit chemical substances on the food ball that may repel fly larvae and certain predators. In the present study, using Deltochilum furcatum, a dung beetle that does not exhibit parental care and the blow-fly, Lucilia cuprina, we tested the hypothesis that pygidial secretions deposited on the food ball could also make it less attractive as an oviposition site for flies. Food balls rolled by either D. furcatum males or females received significantly fewer eggs that balls that had not been rolled by beetles. Also, flies laid significantly fewer eggs on food balls treated with secretions collected from male pygidial glands. Reduced fly oviposition may be a direct effect of compounds the beetles deposited, acting as an allomone, and/or an indirect negative effect on the microbial community that stimulates fly oviposition. A model of the reproductive biology of this species is proposed. | 10.3390/insects9030092 |
pubmed_1086_5550 | The enantiomerically pure alpha-methoxycarbaldehyde 3 was prepared from l-leucine in five steps and 31% overall yield. The aldehyde was subjected to a diastereoselective BF3-mediated crotylation with silane 4 and to various reagent-controlled addition reactions. The configuration of aldol addition products 19 and 20 was proven by single crystal X-ray crystallography. Based on these data spectral comparison allowed an unambiguous assignment of the desired anti,syn-crotylation product 2b and of the syn,syn-crotylation product 2a. Unexpectedly, product 2a of the BF3-mediated crotylation is formally the product of chelation-control. The anti,syn-crotylation product 2b, which is a model for the C-9/C-15 fragment of geldanamycin, was obtained by a reagent-controlled crotylation with the chiral (Z)-crotylborane 23. | 10.1016/j.bmc.2006.05.056 |
pubmed_689_17383 | Loneliness is an important predictor of physical and mental health in the general population and in individuals across the psychosis spectrum, including those experiencing subclinical psychotic-like experiences (PLEs). However, the mechanisms underlying loneliness in the psychosis spectrum are not well understood. Emotion processing deficits are well described across the psychosis spectrum, and socioemotional processing biases are critical for the development and maintenance of loneliness through altered social appraisal, including judgements of rejection. Therefore, we propose that PLEs are associated with increased loneliness, and the relationship is mediated by alterations in socioemotional processing. We also explored how this pathway may be affected by mood and anxiety symptoms, which have been associated with loneliness across the psychosis spectrum. As part of the Human Connectome Project, generally healthy adults (n = 1180) reported symptomatology and social functioning and completed the Penn Emotion Recognition Task to assess efficiency in identifying emotions. We found that higher reported PLEs were associated with elevated levels of loneliness and perceived rejection and that these factors were linked by multiple independent pathways. First, anxiety/depression and emotion processing efficiency independently mediated the PLE-loneliness relationship. Second, we found that the association between PLEs and loneliness was serially mediated through inefficient emotion recognition then higher levels of perceived rejection. These separable mechanisms of increased loneliness in subclinical psychosis have implications for treatment and continued study of social functioning in the psychosis spectrum. | 10.1016/j.schres.2021.10.002 |
pubmed_111_18719 | The sensitivity to ionizing radiation of three human bladder transitional cell carcinomas grown in the nude mouse was investigated at four different radiation levels, 500, 1,000, 2,000 and 4,000 rad. Each tumor line exhibited a response pattern which reflected to a certain degree tumor differentiation and growth rate in the nude mouse. Exposure to 1,000 rad was the minimum amount of radiation required to produce a distinct, although transient, tumor response in all three tumor lines characterized by a growth delay of 3-4 weeks, whereas maximum tumor response was observed at the 4,000 rad radiation level. These studies would permit a better understanding of the behavior of human bladder cancer to ionizing radiation and may further facilitate efforts at identifying effective radiosensitizing agents that may result in maximizing tumor response. | 10.1159/000163323 |
pubmed_625_21039 | The selection of the right antibiotic and right dose necessitates clinicians understand the contribution of pharmacokinetic variability stemming from age-related physiologic maturation and the pharmacodynamics to optimize drug exposure for clinical response. The complexity of selecting the right dose arises from the multiplicity of pediatric age groups, from premature neonates to adolescents. Body size and age (which relate to organ function) must be incorporated to optimize antibiotic dosing in this vulnerable population. In the effort to optimize and individualize drug dosing regimens, clinical pharmacometrics that incorporate population-based pharmacokinetic modeling, Bayesian estimation, and Monte Carlo simulations are utilized as a quantitative approach to understanding and predicting the pharmacology and clinical and microbiologic efficacy of antibiotics. In addition, opportunistic study designs and alternative blood sampling strategies can serve as practical approaches to ensure successful conduct of pediatric studies. This review article examines relevant literature on optimization of antibiotic pharmacotherapy in pediatric populations published within the last decade. Specific pediatric antibiotic data, including beta-lactam antibiotics, aminoglycosides, and vancomycin, are critically evaluated. | 10.1002/jcph.1128 |
pubmed_41_11486 | The response of resistant soil organic matter to temperature change is crucial for predicting climate change impacts on C cycling in terrestrial ecosystems. However, the response of the decomposition of different soil organic carbon (SOC) fractions to temperature is still under debate. To investigate whether the labile and resistant SOC components have different temperature sensitivities, soil samples were collected from three forest and two grass land sites, along with a gradient of latitude from 18°40'to 43°17'N and elevation from 600 to 3510 m across China, and were incubated under changing temperature (from 12 to 32 oC) for at least 260 days. Soil respiration rates were positively related to the content of soil organic carbon and soil microbial carbon. The temperature sensitivity of soil respiration, presented as Q10 value, varies from 1.93 ± 0.15 to 2.60 ± 0.21. During the incubation, there were no significant differences between the Q10 values of soil samples from different layers of the same site, nor a clear pattern of Q10 values along with the gradient of latitude. The result of this study does not support current opinion that resistant soil carbon decomposition is more sensitive to temperature change than labile soil carbon. | 10.1371/journal.pone.0186675 |
pubmed_731_9620 | Congenital human cytomegalovirus (HCMV) is the most common viral infection of the developing fetus, and a significant cause of neurodevelopmental abnormalities in infants and children. Congenital HCMV infections account for an estimated 25% of all cases of hearing loss in the US. It has long been argued that maternal adaptive immune responses to HCMV can modify both the likelihood of intrauterine transmission of HCMV, and the severity of fetal infection and risk of long term sequelae in infected infants. Over the last two decades, multiple studies have challenged this paradigm, including findings that have demonstrated that the vast majority of infants with congenital HCMV infections in most populations are born to women with established immunity prior to conception. Furthermore, the incidence of clinically apparent congenital HCMV infection in infants born to immune and non-immune pregnant women appears to be similar. These findings from natural history studies have important implications for the design, development, and testing of prophylactic vaccines and biologics for this perinatal infection. This brief overview will provide a discussion of existing data from human natural history studies and animal models of congenital HCMV infections that have described the role of maternal immunity in the natural history of this perinatal infection. | 10.3390/v10080405 |
pubmed_162_3174 | Human faces contain multiple sources of information. During speech perception, visual information from the talker's mouth is integrated with auditory information from the talker's voice. By directly recording neural responses from small populations of neurons in patients implanted with subdural electrodes, we found enhanced visual cortex responses to speech when auditory speech was absent (rendering visual speech especially relevant). Receptive field mapping demonstrated that this enhancement was specific to regions of the visual cortex with retinotopic representations of the mouth of the talker. Connectivity between frontal cortex and other brain regions was measured with trial-by-trial power correlations. Strong connectivity was observed between frontal cortex and mouth regions of visual cortex; connectivity was weaker between frontal cortex and non-mouth regions of visual cortex or auditory cortex. These results suggest that top-down selection of visual information from the talker's mouth by frontal cortex plays an important role in audiovisual speech perception. | pubmed_162_3174 |
pubmed_1061_21390 | In Hokkaido, the northernmost region of Japan, soybean [Glycine max (L.) Merr.] crops are damaged by cold weather. Chilling temperatures negatively affect seed appearance by causing seed coat discoloration around the hilum region, which is called cold-induced discoloration (CD). An assay for CD tolerance using a phytotron was developed, and two quantitative trait loci (QTLs) associated with CD tolerance were identified. The major QTL was located in the proximal region of the I locus, and structural variation of this locus can serve as a useful DNA marker, called the Ic marker. To use this marker in breeding programs, the effects need to be assessed under field conditions because the Ic marker has been developed solely under phytotron conditions. The aim of this study was thus to assess the effect of the Ic marker under a cool field environment. We confirmed that the Ic allele was highly effective using 27 cultivars and breeding lines including a near-isogenic line grown in the field where severe cold-weather damage occurred. This allele had no negative influence on the agronomic traits in the near-isogenic line. Our results suggest that marker-assisted selection for the Ic allele is effective for improving CD tolerance in breeding programs. | 10.1270/jsbbs.19024 |
pubmed_140_6111 | Background: Colorectal cancer (CRC) represents a major public health problem owing to the fact that many patients are diagnosed in locally advanced or metastatic stage when chemotherapy is the only remaining option. However, treatment response is still unpredictable and depends upon a diversity of factors such as tumor inherited or acquired drug resistance and the host immune response to the malignant cells. The aim of this study was to evaluate the serum levels of interleukin 6, 8, 10 (IL-6, 8, 10) as possible predictive factors for response to chemotherapy and the correlation between the cytokines and the psychological distress.Methods: Forty-nine patients undergoing chemotherapy for locally advanced or metastatic CRC were included, for each patient IL-6, 8 and 10 were assessed through ELISA. Depression and anxiety were quantified through questionnaires. Statistical data were performed with GraphPad.Results: Patients with CRC had high serum levels of IL-8 and IL-6 compared to the healthy control group. High levels of IL-8 before treatment were correlated with progressive disease. There was a high incidence of psychological complication in CRC patients, especially in young male patients, from an urban area, with a positive correlation between serum levels of IL-8 and depression.Conclusions: These results indicate that high serum levels of IL-8 are predictive factors in CRC patients that undergo chemotherapy, but also could be useful in identifying psychological distress associated with this pathology. | 10.1080/17843286.2019.1680133 |
pubmed_504_15315 | Obesity is a serious public health problem associated with predisposition to develop metabolic diseases. Over the past decade, several studies in vitro and in vivo have shown that the activity of Krüppel-like factors (KLFs) regulates adipogenesis, adipose tissue function and metabolism. Comprehension of both the origin and development of adipocytes and of adipose tissue could provide new insights into therapeutic strategies to contend against obesity and related metabolic diseases. This review focus on the transcriptional role that KLF family members play during adipocyte differentiation, describes their main interactions and the mechanisms involved in this fine-tuned developmental process. We also summarize new findings of the involvement of several effectors that modulate KLFs expression during adipogenesis, including growth factors, circadian clock proteins, interleukins, nuclear receptors, protein kinases and importantly, microRNAs. Thus, KLFs regulation by these factors and emerging molecules might constitute a potential therapeutic target for anti-obesity intervention. | 10.1016/j.lfs.2020.118763 |
pubmed_370_12777 | Ketogenic diets have a high fat and low carbohydrate and low protein content to induce ketosis which is monitored by daily urine testing. Lapses in diet are frequently associated with loss of anticonvulsant control. There has, as yet, been no report of children maintained on a ketogenic diet subject to anaesthesia and surgery: this paper records the changes in metabolic variables observed in three patients undergoing simple inhalation anaesthetics for minor surgery. | 10.1111/j.1365-2044.1982.tb00991.x |
pubmed_92_3226 | BACKGROUND
Older patients account for nearly half of the United States surgical volume, and age alone is insufficient to predict surgical fitness. Various metrics exist for risk stratification, but little work has been done to describe the association between measures. We aimed to determine whether analytic morphomics, a novel objective risk assessment tool, correlates with functional measures currently recommended in the preoperative evaluation of older patients.
MATERIALS AND METHODS
We retrospectively identified 184 elective general surgery patients aged >70 y with both a preoperative computed tomography scan and Vulnerable Elderly Surgical Pathways and outcomes Assessment within 90 d of surgery. We used analytic morphomics to calculate trunk muscle size (or total psoas area [TPA]) and univariate logistic regression to assess the relationship between TPA and domains of geriatric function mobility, basic and instrumental activities of daily living (ADLs), and cognitive ability.
RESULTS
Greater TPA was inversely correlated with impaired mobility (odds ratio [OR] = 0.46, 95% confidence interval [CI] 0.25-0.85, P = 0.013). Greater TPA was associated with decreased odds of deficit in any basic ADLs (OR = 0.36 per standard deviation unit increase in TPA, 95% CI 0.15-0.87, P <0.03) and any instrumental ADLs (OR = 0.53, 95% CI 0.34-0.81; P <0.005). Finally, patients with larger TPA were less likely to have cognitive difficulty assessed by Mini-Cog scale (OR = 0.55, 95% CI 0.35-0.86, P <0.01). Controlling for age did not change results.
CONCLUSIONS
Older surgical candidates with greater trunk muscle size, or greater TPA, are less likely to have physical impairment, cognitive difficulty, or decreased ability to perform daily self-care. Further research linking these assessments to clinical outcomes is needed. | pubmed_92_3226 |
pubmed_856_9599 | Apolipoprotein E (apoE), a major determinant protein for lipid metabolism, actively participates in lipid transport in the central nervous system via high-affinity interaction with the low-density lipoprotein receptor (LDLR). Prior evidences indicate that the phospholipids first need to assemble around apoE before the protein can recognize its receptor. However, despite multiple attempts via spectroscopic and biochemical investigations, it is unclear what are the impacts of lipid assembly on the globular structure of apoE. Here, using a combination of all-atom and coarse-grained molecular dynamics simulations, we demonstrate that an otherwise compact tertiary fold of monomeric apoE3 spontaneously unwraps in an aqueous phospholipid solution in two distinct stages. Interestingly, these structural reorganizations are triggered by an initial localized binding of lipid molecules to the C-terminal domain of the protein, which induce a rapid separation of the C-terminal domain of apoE3 from the rest of its tertiary fold. This is followed by a slow lipid-induced interhelix separation event within the N-terminal domain of the protein, as seen in an extensively long coarse-grained simulation. Remarkably, the resultant complex takes the shape of an "open conformation" of the lipid-stabilized unwrapped protein, which intriguingly coincides with an earlier proposal by a small-angle X-ray scattering (SAXS) experiment. The lipid-binding activity and the lipid-induced protein conformation are found to be robust across a monomeric mutant and wild-type sequence of apoE3. The "open" complex derived in coarse-grained simulation retains its structural morphology after reverse-mapping to the all-atom representation. Collectively, the investigation puts forward a plausible structure of currently elusive conformationally activated state of apoE3, which is primed for recognition by the lipoprotein receptor and can be exploited for eventual lipid transport. | 10.1021/acs.jpcb.1c03011 |
pubmed_33_2834 | PCR in bronchoalveolar lavage (BAL) fluid has not been accepted as a diagnostic criterion for invasive pulmonary aspergillosis (IPA). We conducted a systematic review assessing the diagnostic accuracy of PCR in BAL fluid with a direct comparison versus galactomannan (GM) in BAL fluid. We included prospective and retrospective cohort and case-control studies. Studies were included if they used the EORTC/MSG consensus definition criteria of IPA and assessed ≥80% of patients at risk for IPA. Two reviewers abstracted data independently. Risk of bias was assessed using QUADAS-2. Summary sensitivity and specificity values were estimated using a bivariate model and reported with a 95% confidence interval (CI). Nineteen studies published between 1993 and 2012 were included. The summary sensitivity and specificity values (CIs) for diagnosis of proven or probable IPA were 90.2% (77.2 to 96.1%) and 96.4% (93.3 to 98.1%), respectively. In nine cohort studies strictly adherent to the 2002 or 2008 EORTC/MSG criteria for reference standard definitions, the summary sensitivity and specificity values (CIs) were 77.2% (62 to 87.6%) and 93.5% (90.6 to 95.6%), respectively. Antifungal treatment before bronchoscopy significantly reduced sensitivity. The diagnostic performance of PCR was similar to that of GM in BAL fluid using an optical density index cutoff of 0.5. If either PCR or GM in BAL fluid defined a positive result, the pooled sensitivity was higher than that of GM alone, with similar specificity. We conclude that the diagnostic performance of PCR in BAL fluid is good and comparable to that of GM in BAL fluid. Performing both tests results in optimal sensitivity with no loss of specificity. Results are dependent on the reference standard definitions. | 10.1128/JCM.00942-12 |
pubmed_634_6999 | PURPOSE OF REVIEW
The aim if this review is to provide an update on the existing literature of animal bite treatment strategies and provide a systematic approach to animal bites from presentation to reconstruction.
RECENT FINDINGS
Dog bites cause 80-90% of animal bites with 26.8-56.5% occurring in the head and neck. Infection rates may be as low as 5.7-9.7%. Primary closure alone is sufficient in 69.8% of dog bites within the first 24 h.
SUMMARY
Animal bite injuries to the head and neck are common, especially in the younger population. Dogs cause a majority of these bite injuries. Injuries can include simple lacerations or punctures, avulsions with tissue present, or avulsions with loss of tissue. The most common locations are the cheek, nose, and lips. It is important to gather the vaccination status of the animal and patient and to administer tetanus/rabies prophylaxis if indicated. Antibiotics are typically prescribed for 3-5 and 7-14 days for uninfected and infected wounds, respectively. These wounds require evaluation, irrigation, and occasionally debridement or repair in the operating room. The type of repair is determined based on the location and extent of injury and can range from primary closure to microsurgical replantation, skin grafts, flaps, or even facial transplantation. | 10.1097/MOO.0000000000000564 |
pubmed_740_4422 | Background
Enterococcus faecium is an important nosocomial pathogen. It has a high propensity for horizontal gene transfer, which has resulted in the emergence of MDR strains that are difficult to treat. The most notorious of these, vancomycin-resistant E. faecium, are usually treated with linezolid or daptomycin. Resistance has, however, been reported, meaning that new therapeutics are urgently needed. The 1,2,4-oxadiazoles are a recently discovered family of antimicrobials that are active against Gram-positive pathogens and therefore have therapeutic potential for treating E. faecium. However, only limited data are available on the activity of these antimicrobials against E. faecium.
Objectives
To determine whether the 1,2,4-oxadiazole antimicrobials are active against MDR and daptomycin-non-susceptible E. faecium.
Methods
The activity of the 1,2,4-oxadiazole antimicrobials against vancomycin-susceptible, vancomycin-resistant and daptomycin-non-susceptible E. faecium was determined using susceptibility testing, time-kill assays and synergy assays. Toxicity was also evaluated against human cells by XTT and haemolysis assays.
Results
The 1,2,4-oxadiazoles are active against a range of MDR E. faecium, including isolates that display non-susceptibility to vancomycin and daptomycin. This class of antimicrobial displays rapid bactericidal activity and demonstrates superior killing of E. faecium compared with daptomycin. Finally, the 1,2,4-oxadiazoles act synergistically with daptomycin against E. faecium, with subinhibitory concentrations reducing the MIC of daptomycin for non-susceptible isolates to a level below the clinical breakpoint.
Conclusions
The 1,2,4-oxadiazoles are active against MDR and daptomycin-non-susceptible E. faecium and hold great promise as future therapeutics for treating infections caused by these difficult-to-treat isolates. | 10.1093/jac/dky064 |
pubmed_869_18082 | The aim of this work was to identify the influence of tablet density on their gastric emptying in fasted subjects and to compare the findings with those of a previous study using the same subjects with tablets of a larger diameter. Tablets of 6.6 mm diameter and densities of 1.41 and 2.85 g cm-3 were labelled with 99mTc and 111In. They were coated with ethyl cellulose to ensure that they remained intact within the gastrointestinal tract. Their position within the gastrointestinal tract of fasted healthy subjects was monitored with a double-headed gamma camera at 1-min time intervals. The median gastric emptying time and the interquartile range were derived from the Bernoulli random event distribution. It was found that the dense tablets had a significantly longer gastric emptying time than the light tablets. Comparison with the results from the previous study gave a clear indication that irrespective of tablet density, the 6.6-mm tablets had longer gastric emptying times than the 12.0-mm tablets. | 10.1211/jpp.59.1.0004 |
pubmed_938_5340 | A peptide (called A-15) composed of 15 amino acids of the gp41 (from position 599 to position 613 of the sequence encoded by the env gene) of HIV-1 has been used as an antigen to search for antibodies in 347 sera of at-risk for HIV-1 infection subjects. The purpose was of comparing the prevalence of these antibodies with that of HIV-1 total EIA antibodies and HIV-1 immunoblotting antibodies. Assuming immunoblotting test as reference test for detecting a HIV-1 infection, the antibodies against peptide A-15 show the same sensitivity and specificity when compared with other HIV-1 total EIA antibodies tests. | pubmed_938_5340 |
pubmed_986_9173 | Male Long-Evans rats that had been exposed in utero to 5 or 8 mg/kg of methyl mercury administered as a single dose on either days 8 or 15 of gestation were tested as adults in two operant tasks. In one task the animals were trained on two-way avoidance to a criterion of 10 consecutive avoidances. Following acquisition the animals were extinguished and 24 hours later re-trained to the previous criterion. Animals treated with 8 mg/kg on day 8 of gestation required significantly more trials to reach criterion during reacquisition than controls. Rats treated on day 15 with either 5 or 8 mg/kg took significantly more trials to reach criterion during acquisition than controls, and of the 8 mg/kg group 55% failed to reach criterion. Rats treated with 8 mg/kg of mercury on day 8 of gestation acquired a DRL-10 sec task at the same rate as controls. When challenged with d-amphetamine the treated animals were less disrupted at the higher dose (1.0 mg/kg) than controls, suggesting a shift in the dose response curve for this psychoactive drug. Activity measures taken simultaneously with the DRL session confirmed this shift in amphetamine effect. Results suggest that a single prenatal exposure to methyl mercury can affect learning and drug sensitivity of the adult animal. Additionally, mercury exposure in late gestation has more deleterious consequences on learning ability than early exposure. | pubmed_986_9173 |
pubmed_333_13234 | Controversy exists regarding the correct time of removal of an alginate impression from the mouth. To investigate the effect of time of removal on accuracy, a series of alginate impressions were made of the lower left quadrant of a subject having a cast gold crown with four reference marks on tooth no. 19. The impressions were removed from the mouth at 1-5, 2, 3, 4-5 and 7 min after the insertion of the tray. Accuracy of the impressions was assessed by comparing the distances between the reference marks in stone casts with standard measurements taken from the gold crown prior to cementation. Impressions removed at 1-5 and 7 min produced the greatest distortions buccolingually. For the mesio-distal lengths all time intervals produced casts which were larger than the standard. The reasons for these findings are discussed and possible explanations are presented. | 10.1111/j.1365-2842.1977.tb01002.x |
pubmed_63_4407 | BACKGROUND
The rate at which neutral (non-functional) bases undergo substitution is highly dependent on their location within a genome. However, it is not clear how fast these location-dependent rates change, or to what extent the substitution rate patterns are conserved between lineages. To address this question, which is critical not only for understanding the substitution process but also for evaluating phylogenetic footprinting algorithms, we examine ancestral repeats: a predominantly neutral dataset with a significantly higher genomic density than other datasets commonly used to study substitution rate variation. Using this repeat data, we measure the extent to which orthologous ancestral repeat sequences exhibit similar substitution patterns in separate mammalian lineages, allowing us to ascertain how well local substitution rates have been preserved across species.
RESULTS
We calculated substitution rates for each ancestral repeat in each of three independent mammalian lineages (primate - from human/macaque alignments, rodent - from mouse/rat alignments, and laurasiatheria - from dog/cow alignments). We then measured the correlation of local substitution rates among these lineages. Overall we found the correlations between lineages to be statistically significant, but too weak to have much predictive power (r2 <5%). These correlations were found to be primarily driven by regional effects at the scale of several hundred kb or larger. A few repeat classes (e.g. 7SK, Charlie8, and MER121) also exhibited stronger conservation of rate patterns, likely due to the effect of repeat-specific purifying selection. These classes should be excluded when estimating local neutral substitution rates.
CONCLUSION
Although local neutral substitution rates have some correlations among mammalian species, these correlations have little predictive power on the scale of individual repeats. This indicates that local substitution rates have changed significantly among the lineages we have studied, and are likely to have changed even more for more diverged lineages. The correlations that do persist are too weak to be responsible for many of the highly conserved elements found by phylogenetic footprinting algorithms, leading us to conclude that such elements must be conserved due to selective forces. | 10.1186/1471-2148-9-89 |
pubmed_993_10393 | Nine children admitted with typhoid perforation of the ileum underwent a modified ileostomy procedure. The following conclusions were drawn: 1. X-rays do not help in diagnosis in the majority of cases. 2. Blood urea is raised in almost all cases and vigorous attempts should be made to bring its level to normal before operation. 3. Leukopenia does not exist in patients with typhoid perforation; leukocytosis is the usual finding. A positive Widal test is not generally found in these cases and positive blood cultures should not be expected. 4. Ileostomy through the site of perforation, as described, is a simple, safe and short operation in a critically ill patient with a necrotic bowel. Also, resuscitative drugs are not needed. | pubmed_993_10393 |
pubmed_1022_4739 | Pattern-mixture models provide a general and flexible framework for sensitivity analyses of nonignorable missing data in longitudinal studies. The placebo-based pattern-mixture model handles missing data in a transparent and clinically interpretable manner. We extend this model to include a sensitivity parameter that characterizes the gradual departure of the missing data mechanism from being missing at random toward being missing not at random under the standard placebo-based pattern-mixture model. We derive the treatment effect implied by the extended model. We propose to utilize the primary analysis based on a mixed-effects model for repeated measures to draw inference about the treatment effect under the extended placebo-based pattern-mixture model. We use simulation studies to confirm the validity of the proposed method. We apply the proposed method to a clinical study of major depressive disorders. | 10.1002/pst.1605 |
pubmed_737_7667 | Cyclic peptides are exciting novel hosts for chiral and molecular recognition. In this work, the inclusion complexes of cyclic decapeptide (CDP) with the 1-phenyl-1-propanol enantiomers (E-PP) are firstly studied using the density functional theory (DFT) B3LYP method. Our calculated results indicated that S(-)-1-phenyl-1-propanol (S-PP) could form a more stable inclusion complex with CDP than that of R(+)-1-phenyl-1-propanol (R-PP). The obvious differences in binding energy and thermodynamics data suggest that the cyclic decapeptide could differentiate the two enantiomers. Furthermore, molecular dynamics simulation results have supported the conclusions obtained by DFT. The current investigation shows that cyclic peptide is a desirable host molecule for chiral and molecular recognition. | 10.1007/s00894-011-1119-z |
pubmed_438_20139 | Using cardiac troponin T(cTnT), a highly sensitive and specific marker of myocardial injury, we evaluated the effects of ischemic precondition on ischemic reperfusion myocardial injury. Thirty two patients were randomly divided into control group(n = 16) and ischemic preconditioning group(n = 16). The marker cTnT was measured in each group before operation, and 4 h, 24 h and 72 h after operation. The results showed that the peak value of cTnT was lower, and more quickly recovered in the preconditioning group than that in the control. It is suggested that ischemic preconditioning exert an evidently protective effect on ischemic reperfusion myocardial injury. | pubmed_438_20139 |
pubmed_130_6633 | Radiation-induced lung injury (RILI) is a common complication of radiotherapy for thoracic tumor. Its incidence rate is as high as 20%. At present, there is no effective treatment in clinical practice. However, to study the mechanism of radiation-induced lung injury, we should first establish an appropriate animal model. In a series of scientific studies on RILI, mice are the animals most often chosen by researchers. However, there are few reports on which strain of mice is more suitable as a model of RILI. In this study, Kunming (KM) and C57BL/6 strains of mice were used as research objects to find the most suitable mice to replicate the RILI model. C57BL/6 mice and KM mice were exposed to irradiation at a dose of 20 Gy. The lung tissue of C57BL/6 mice exposed to radiation showed dilation and hyperemia of capillaries, infiltration of inflammatory cells, and thickening of alveolar septum, while the lung tissue of KM mice exposed to radiation was not as obvious as that of C57BL/6 mice. After irradiation, the expression of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in the lung tissue of C57BL/6 mice was significantly increased, while the expression of IL-6 and TNF-α in KM mice was almost unchanged. These studies showed that C57BL/6 mice are more suitable for the model of radiation-induced lung injury because of sensitive inflammatory reaction and the pathological changes of lung tissue. | 10.1097/HP.0000000000001532 |
pubmed_1061_3385 | Biological assemblies such as chromosomes, membranes, and the cytoskeleton are driven out of equilibrium at the nanoscale by enzymatic activity and molecular motors. Similar non-equilibrium dynamics can be realized in synthetic systems, such as chemically fueled colloidal particles. Characterizing the stochastic non-equilibrium dynamics of such active soft assemblies still remains a challenge. Recently, new non-invasive approaches have been proposed to determine the non-equilibrium behavior, which are based on detecting broken detailed balance in the stochastic trajectories of several coordinates of the system. Inspired by the method of two-point microrheology, in which the equilibrium fluctuations of a pair of probe particles reveal the viscoelastic response of an equilibrium system, here, we investigate whether we can extend such an approach to non-equilibrium assemblies: can one extract information on the nature of the active driving in a system from the analysis of a two-point non-equilibrium measure? We address this question theoretically in the context of a class of elastic systems, driven out of equilibrium by a spatially heterogeneous stochastic internal driving. We consider several scenarios for the spatial features of the internal driving that may be relevant in biological and synthetic systems, and investigate how such features of the active noise may be reflected in the long-range scaling behavior of two-point non-equilibrium measures. | 10.1039/c9sm01169b |
pubmed_386_2275 | PURPOSE
To enhance speedy communication between the patient and the doctor through newly proposed routing protocol at the mobile node.
MATERIALS AND METHODS
The proposed model is applied for a telemedicine application during disaster recovery management. In this paper, Energy Efficient Link Stability Routing Protocol (EELSRP) has been developed by simulation and real time. This framework is designed for the immediate healing of affected persons in remote areas, especially at the time of the disaster where there is no hospital proximity. In case of disasters, there might be an outbreak of infectious diseases. In such cases, the patient's medical record is also transferred by the field operator from disaster place to the hospital to facilitate the identification of the disease-causing agent and to prescribe the necessary medication. The heterogeneous networking framework provides reliable, energy efficientand speedy communication between the patient and the doctor using the proposed routing protocol at the mobile node.
RESULTS
The performance of the simulation and real time versions of the Energy Efficient Link Stability Routing Protocol (EELSRP) protocol has been analyzed. Experimental results prove the efficiency of the real-time version of EESLRP protocol.
CONCLUSION
The packet delivery ratio and throughput of the real time version of EELSRP protocol is increased by 3% and 10%, respectively, when compared to the simulated version of EELSRP. The end-to-end delay and energy consumption are reduced by 10% and 2% in the real time version of EELSRP. | 10.4103/0255-0857.150871 |
pubmed_359_650 | A competitive method to evaluate the reactivity of highly reactive antioxidants is reported. Pyrogallol red (PGR) and AAPH (2,2'-azo-bis-(2-amidinopropane) dihydrochloride) were employed as target-molecule and peroxyl radical source, respectively. In the zero-order kinetic limit in PGR, the dependence of the ratio R(o)/R (where R(o) is the rate of the process in the absence of additive and R is the rate of the process in the presence of additive) upon the additive concentration (Stern-Volmer like plots) was studied. Various polyphenols (n=10) and ascorbic acid (AA) were tested as additives. In PGR protection by AA, was observed a neat induction time, associated to the total protection of the target molecule. On the other hand, the experiments that were carried out in presence of phenolic compounds allowed a relative evaluation of their reactivity towards peroxyl radicals. This reactivity follows the order quercetin > gallic acid > Trolox > kaempferol. Data obtained employing quercetin and Trolox are compatible with a competitive protection by these antioxidants. Due to the high reactivity of PGR towards peroxyl radicals and its high extinction coefficient at long wavelengths, it is a very suitable molecule to be employed as target in the evaluation of the free radical scavenging capability of very reactive phenolic compounds. | 10.1080/10715760500143452 |
pubmed_629_18459 | Glycosidases are enzymes with a potential role in embryonic development. The objectives of this study were to assess: (a) whether in vitro bovine embryonic development is affected by the addition of beta-N-acetyloglucosaminidase (beta-NAGASE) and/or alpha-mannosidase to the culture medium and (b) whether these enzymes are utilized by bovine embryos during their development in vitro. Bovine embryos were produced using standard methods of IVM, IVF and IVC. Presumptive zygotes were cultured in groups of 20 in 50 microl drops of SOF medium (plus 5% FBS after 24 h culture) incubated in 5% CO2, 5% O2 and 90% N2 at 38.5 degrees C. The groups of zygotes were allocated to four treatments in which the culture medium was supplemented with: (1) beta-NAGASE, (2) alpha-mannosidase, (3) beta-NAGASE plus alpha-mannosidase, and (4) control (no supplement). Embryos were evaluated and samples of culture medium collected and frozen prior to assay for glycosidases at day 7 of culture. The experimental design was a randomised block arrangement of 4 treatments x 7 replicates with 20 zygotes per plot (culture droplet). Data were analysed by ANOVA and presented as mean +/- S.E.M. The osmolarity of the control culture medium was 272 mOsm. This was increased to 279 mOsm by the addition of alpha-mannosidase, 424 mOsm by beta-NAGASE and 337 mOsm with a combination of the two enzymes. The beta-NAGASE supplemented medium and the combined supplement reduced (0%) the development of zygotes to morula or blastocyst stages (P < 0.002) relative to control medium (35.7 +/- 8.4%). Embryo development was also reduced to 21.9 +/- 3.2 (P< 0.002), relative to control, by alpha-mannosidase supplementation. The reduced embryo development in the beta-NAGASE-supplemented medium was attributed to increased osmolarity of the culture medium. Embryos appeared to utilize alpha-mannosidase because its concentration decreased from 600.95 +/- 174.03 IU/l in drops without zygotes/embryos to 211.01 +/- 71.59 IU/l in drops with zygotes/embryos. Other culture media supplementation showed no significant differences between droplets, with or without zygotes/embryos. It was concluded that beta-NAGASE increased medium osmolarity, embryos utilized alpha-mannosidase and both glycosidases (singly or in combination) inhibited the development of bovine zygotes to morulae/blastocysts. | 10.1016/j.anireprosci.2006.06.002 |
pubmed_893_12162 | We report here the main characteristics of "Streptomyces massilialgeriensis" strain S35T (CSUR = P3927), a new bacterial species within the Streptomyces genus, isolated from an extremely saline soil sample collected from the site of Garaet Ank Djemel in the Wilaya of Oum El Bouaghi, Algeria. | 10.1016/j.nmni.2017.10.003 |
pubmed_617_6317 | PURPOSE
The present study was performed to investigate the effects of the nutrition screening index and pulmonary function test data for patients who underwent surgery for esophageal cancer, based on the incidence of postoperative complications and the duration of postoperative hospitalization.
SUBJECTS AND METHODS
A total of 69 patients who received esophageal cancer resection were included in the study. It was determined how the parameters studied (ie, between ages, concomitant diabetes mellitus, body mass index( BMI), serum albumin level, Onodera's prognostic nutritional index, percentage of vital capacity(%VC), and forced expiratory volume[ FEV]1.0%) were related to the incidence of complications and the duration of postoperative hospital days, as expressed by the median days for all patients and the frequency of long-term hospitalization.
RESULTS
The incidence of postoperative complications was significantly higher in patients aged 65 and above and those with a %VC value of less than 80%. The median duration of postoperative hospitalization was longer in those aged 65 and above and those with a FEV1.0% value of less than 70%, which was related to BMI. In addition, the frequency of long-term hospitalization was higher in those aged 65 and above, which was also related to BMI.
CONCLUSIONS
The results of the present study confirm that postoperative complications and length of postoperative hospital stay in patients with surgically treated esophageal cancer were largely dependent on their pulmonary function as well as age and BMI used for the nutrition screening index. Nutrition screening combined with pulmonary function tests, using age, BMI, %VC, and FEV1.0%, is considered desirable to avoid postoperative complications associated with esophageal cancer. | pubmed_617_6317 |
pubmed_476_15452 | BACKGROUND
Osteoporosis is a common metabolic skeletal disease and usually lacks obvious symptoms. Many individuals are not diagnosed until osteoporotic fractures occur. Bone mineral density (BMD) measured by dual-energy X-ray absorptiometry (DXA) is the gold standard for osteoporosis detection. However, only a limited percentage of people with osteoporosis risks undergo the DXA test. As a result, it is vital to develop methods to identify individuals at-risk based on methods other than DXA.
RESULTS
We proposed a hierarchical model with three layers to detect osteoporosis using clinical data (including demographic characteristics and routine laboratory tests data) and CT images covering lumbar vertebral bodies rather than DXA data via machine learning. 2210 individuals over age 40 were collected retrospectively, among which 246 individuals' clinical data and CT images are both available. Irrelevant and redundant features were removed via statistical analysis. Consequently, 28 features, including 16 clinical data and 12 texture features demonstrated statistically significant differences (p < 0.05) between osteoporosis and normal groups. Six machine learning algorithms including logistic regression (LR), support vector machine with radial-basis function kernel, artificial neural network, random forests, eXtreme Gradient Boosting and Stacking that combined the above five classifiers were employed as classifiers to assess the performances of the model. Furthermore, to diminish the influence of data partitioning, the dataset was randomly split into training and test set with stratified sampling repeated five times. The results demonstrated that the hierarchical model based on LR showed better performances with an area under the receiver operating characteristic curve of 0.818, 0.838, and 0.962 for three layers, respectively in distinguishing individuals with osteoporosis and normal BMD.
CONCLUSIONS
The proposed model showed great potential in opportunistic screening for osteoporosis without additional expense. It is hoped that this model could serve to detect osteoporosis as early as possible and thereby prevent serious complications of osteoporosis, such as osteoporosis fractures. | 10.1186/s12859-022-04596-z |
pubmed_612_8251 | A novel insecticide flupyrimin (FLP) with a trifluoroacetyl pharmacophore acts as an antagonist at the insect nicotinic acetylcholine receptor (nAChR). This investigation examines a hypothesis that the FLP C(O)CF3 moiety is primarily recognized by the β subunit-face in the ligand-binding pocket (interface between α and β subunits) of the insect nAChR. Accordingly, we evaluate the atomic interaction between a fluorine atom of FLP and the partnering amino acid side chain on the β subunit employing a recombinant hybrid nAChR consisting of aphid Mpα2 and rat Rβ2 subunits (with a mutation at T77 on the Rβ2). The H-donating T77R, T77K, T77N, or T77Q nAChR enhances the FLP binding potency relative to that of the wild-type receptor, whereas the affinity of neonicotinoid imidaclprid (IMI) with a nitroguanidine pharmacophore remains unchanged. These results facilitate the establishment of the unique FLP molecular recognition at the Mpα2/Mpβ1 interface structural model, thereby underscoring a distinction in its binding mechanism from IMI. | 10.1021/acs.jafc.1c03241 |
pubmed_378_5835 | This article briefly describes the fundamental principles and some of the clinical applications of interpersonal psychotherapy (IPT), a time-limited, empirically validated treatment for mood disorders. IPT has been tested with general success in a series of clinical trials for mood and, increasingly, non-mood disorders; as both an acute and maintenance treatment; and in differing treatment formats. As a result of this research success, IPT is spreading from research trials to clinical practice in various countries around the world. | pubmed_378_5835 |
pubmed_495_3251 | Antoni J. Rolle (1829-1894) physician, writer and historian was living in Kamieniec Podolski. Many remembrances of Rolle his wife Idalia presented to the Museum of the Medical Faculty of Jagellonian University. Centernary of Rolle's death occurs the opportunity to remember this eminent personality. | pubmed_495_3251 |
pubmed_175_1730 | Skeletal muscle phosphorus-31 31 P MRS is the oldest MRS methodology to be applied to in vivo metabolic research. The technical requirements of 31 P MRS in skeletal muscle depend on the research question, and to assess those questions requires understanding both the relevant muscle physiology, and how 31 P MRS methods can probe it. Here we consider basic signal-acquisition parameters related to radio frequency excitation, TR, TE, spectral resolution, shim and localisation. We make specific recommendations for studies of resting and exercising muscle, including magnetisation transfer, and for data processing. We summarise the metabolic information that can be quantitatively assessed with 31 P MRS, either measured directly or derived by calculations that depend on particular metabolic models, and we give advice on potential problems of interpretation. We give expected values and tolerable ranges for some measured quantities, and minimum requirements for reporting acquisition parameters and experimental results in publications. Reliable examination depends on a reproducible setup, standardised preconditioning of the subject, and careful control of potential difficulties, and we summarise some important considerations and potential confounders. Our recommendations include the quantification and standardisation of contraction intensity, and how best to account for heterogeneous muscle recruitment. We highlight some pitfalls in the assessment of mitochondrial function by analysis of phosphocreatine (PCr) recovery kinetics. Finally, we outline how complementary techniques (near-infrared spectroscopy, arterial spin labelling, BOLD and various other MRI and 1 H MRS measurements) can help in the physiological/metabolic interpretation of 31 P MRS studies by providing information about blood flow and oxygen delivery/utilisation. Our recommendations will assist in achieving the fullest possible reliable picture of muscle physiology and pathophysiology. | 10.1002/nbm.4246 |
pubmed_52_18620 | This work aimed at characterizing the modifications in adolescents nutritional status, growth evolution and education along time and the correlation with the height, weight and body mass index. Data came from 2616 male adolescents soldiers between 17 and 19 years old enlisted for Armed Services in the city of Viçosa-Minas Gerais, Brazil, between 1995 and 2004. There was a positive secular trend for height and weight, with a 4cm and 3kg median increment, respectively, along time. There was a reduction from 28.0% to 11.6% on the prevalence of short stature in the period. It was estimated positive correlation (p < 0.05) between education and stature, weight and BMI. The prevalence of weight excess (risk of overweight and overweight) increased from 7.1% (1995) to 9.1% (2004). Although it was observed positive secular trend for stature and weight, it was not sufficient to reach the median of the National Center for Health Statistics/Center for Disease Control and Prevention. Weight excess and short stature prevalence must be monitored, being necessary the implementation of measures that focus to prevent these disturbance and aim at reaching or maintaining an adequate nutritional state for future generations. | pubmed_52_18620 |
pubmed_1030_17949 | Lymphatic vessel contractions generate net antegrade pulsatile lymph flow. By contrast, impaired lymphatic vessels are often associated with lymphoedema and altered lymph flow. The effect of lymphoedema on the lymph flow field and endothelium is not completely known. Here, we characterized the lymphatic flow field of a platelet-specific receptor C-type lectin-like receptor 2 (CLEC2) deficient lymphoedema mouse model. In regions of lymphoedema, collecting vessels were significantly distended, vessel contractility was greatly diminished and pulsatile lymph flow was replaced by quasi-steady flow. In vitro exposure of human dermal lymphatic endothelial cells (LECs) to lymphoedema-like quasi-steady flow conditions increased intercellular gap formation and permeability in comparison to normal pulsatile lymph flow. In the absence of flow, LECs exposed to steady pressure (SP) increased intercellular gap formation in contrast with pulsatile pressure (PP). The absence of pulsatility in steady fluid flow and SP conditions without flow-induced upregulation of myosin light chain (MLCs) regulatory subunits 9 and 12B mRNA expression and phosphorylation of MLCs, in contrast with pulsatile flow and PP without flow. These studies reveal that the loss of pulsatility, which can occur with lymphoedema, causes LEC contraction and an increase in intercellular gap formation mediated by MLC phosphorylation. | 10.1098/rsif.2022.0223 |
pubmed_832_16004 | Early identification of gastric precancerous lesions, including atrophic gastritis (AG) and intestinal metaplasia (IM), may improve gastric cancer detection and prevention. Because AG and IM are generally asymptomatic, many of the estimated 15 million Americans who carry these lesions remain undiagnosed.1 AG and IM are associated with either active or prior Helicobacter pylori (Hp) infection. Hp infection leads to perturbations in the serum concentration of gastric hormones pepsinogen I (PGI), pepsinogen II, the pepsinogen I/II ratio (PGR), gastrin-17 (G-17), and Hp IgG.2,3 In East Asia and other regions with high burden of Hp infection and gastric cancer, these biomarkers have been used as screening tools for AG and IM.4 However, there exists limited data on the sensitivity and discrimination of these serologic markers in low-Hp-prevalence populations, such as the United States. | 10.1016/j.cgh.2021.01.009 |
pubmed_990_17274 | Neuropeptide Y (NPY), a 36-amino acid peptide, is present in some hippocampal interneurons and nerve terminals and seems to modulate glutamatergic transmission in this structure. Earlier studies of some other authors showed an increase in NPY expression in the hippocampus during seizures and activation of ionotropic glutamate receptors. In the present study the effect of metabotropic glutamate receptor (mGluR) stimulation was investigated in rat hippocampus by immunohistochemical methods. It was found that (1S,3R)1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD), a selective agonist of mGluRs injected into the rat lateral ventricle (1 mumol/10 microliters) or hippocampus (0.1 mumol/1 microliter), 24 h before taking the brains for immunohistochemical studies, induced a significant increase in NPY-immunoreactivity in the hippocampus, especially in the hilar region. The obtained results indicate that mGluRs positively modulate the NPY content in the hippocampal neurons. | pubmed_990_17274 |
pubmed_300_11099 | Syphilis has been referred to as the great imitator, the great mimic, and the great masquerader. It often presents with clinical and histological findings similar to many other dermatological conditions. We report a patient presenting with nodular plaques, a rare form of secondary syphilis. The histological features revealed a pseudolymphoma mimicking a cutaneous marginal zone B-cell lymphoma. Syphilis should be considered in the differential diagnosis of a cutaneous lymphoreticular process. | 10.1097/DAD.0b013e3181ad4f22 |
pubmed_1026_11655 | Migraine is a multifaceted brain disorder where multisensory disturbances are associated with headache. Yet sensory symptoms are conventionally justified by dysfunctions confined to the cerebral cortex, a perspective through the complex interplay of thalamocortical network would provide the entire picture, more pertinent to the central sensory processing. It is important to consider thalamus as a hub that integrates multiple domains via extensive connections among anatomically and functionally separate cortical areas. Accordingly, cortical spreading depression (CSD), implicated in migraine pathophysiology can be seen as a tool to disconnect thalamocortical network by functionally eliminating cerebral cortex. Hence, including thalamic reticular nucleus and higher order thalamic nuclei, which conveys the information transthalamically among visual, somatosensory, language and motor cortical areas, would greatly improve our current understanding of migraine. | 10.3906/sag-2005-21 |
pubmed_172_14042 | GTP-binding protein(s) assayed by [35S]GTP gamma S was detected in the extract of Lemna paucicostata containing membrane components. About 15% of [35S]GTP gamma S activated GTP-binding protein, separated from unbound [35S]GTP gamma S by gel filtration, was retained on Millipore HAWP membrane filter. 80% of [35S]GTP gamma S activated protein, mixed with charcoal solution, remained in the supernatant after centrifugation of the mixture. Successive treatments of the assay mixture by charcoal solution established the assay system for the activation of GTP-binding protein. The Km value for the activation of GTP-binding protein was 8 nM. | 10.1016/0006-291x(87)90335-4 |
pubmed_449_8702 | Human muscle (HM) was used in an organ culture system to study the growth of human tumor cells and to test an antitumor drug. The HM system mimicked the in vivo situation regarding the behavior of neoplastic versus normal cells in that tumor cells proliferated extensively and invaded, while normal cells showed only a limited proliferative potential and a limited invasion was observed with fibroblasts but not with epithelial cells. In addition, when human plasma (HP) was used in place of fetal bovine serum (FBS) and cell culture medium as a source of nutrients, the tumor cells displayed a more aggressive histopathologic pattern. The HM system, as illustrated by the 5-FU results, allows the direct visualization of the effect to an antitumor agent not only on tumor cell growth but also on a range of histopathologically evaluable characteristics of the interaction of tumor cells with the host tissue. The HM system provides for the first time an in vitro experimental model using easily accessible adult human tissue to study cancer and its treatment. | 10.1007/BF00177412 |
pubmed_703_197 | Staphylococcus epidermidis is a leading cause of hospital-acquired infections, mostly associated with the use of medical devices in seriously ill or immunocompromised patients. Currently, the characteristics of methicillin-resistant S. epidermidis (MRSE) isolates from Rio de Janeiro hospitals are unknown. In this study, staphylococcal chromosomal cassette mec (SCCmec) types, antimicrobial susceptibility profiles, biofilm formation genes, and multilocus sequence types (MLST) were investigated in 35 MRSE clinical isolates. The collection of isolates was previously well characterized by pulsed-field gel electrophoresis (PFGE) into 2 main genotypes (A and B, 22 isolates) and 10 sporadic genotypes (13 isolates). MLST revealed a total of 8 different sequence types (STs), but ST2 and ST23, which were icaAB-positive, represented the majority (71.4%) of MRSE isolates tested. Almost all isolates (91.4%) belonged to clonal complex 2. SCCmec types III and IV were identified among 71.4% of the isolates, while the remaining was nontypeable. The predominant MRSE genotypes were defined as SCCmec type III/ST2 (PFGE type A) and SCCmec type IV/ST23 (PFGE type B) isolates, which were both associated with high antimicrobial resistance and presence of biofilm-related genes. | 10.1016/j.diagmicrobio.2011.09.017 |
pubmed_372_20859 | To evaluate the ability of a commercialized deep learning reconstruction technique to depict intracranial vessels on the brain computed tomography angiography and compare the image quality with filtered-back-projection and hybrid iterative reconstruction in terms of objective and subjective measures. Forty-three patients underwent brain computed tomography angiography, and images were reconstructed using three algorithms: filtered-back-projection, hybrid iterative reconstruction, and deep learning reconstruction. The image noise, computed tomography attenuation value, signal-to-noise ratio, and contrast-to-noise ratio were measured in the bilateral cavernous segment of the internal carotid artery, vertebral artery, basilar apex, horizontal segment of the middle cerebral artery and used for the objective assessment of the image quality among the three different reconstructions. The subjective image quality score was significantly higher for the deep learning reconstruction than hybrid iterative reconstruction and filtered-back-projection images. The deep learning reconstruction markedly improved the reduction of blooming artifacts in surgical clips and coiled aneurysms. The deep learning reconstruction method generally improves the image quality of brain computed tomography angiography in terms of objective measurement and subjective grading compared with filtered-back-projection and hybrid iterative reconstruction. Especially, deep learning reconstruction is deemed advantageous for better depiction of small vessels compared to filtered-back projection and hybrid iterative reconstruction. | 10.31083/j.jin2004097 |
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