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pubmed_575_20856 | PURPOSE
Inguinal hernia is a common male surgical disease. Intervention carries a wide range of complications such as scrotal haematoma and seroma which may require surgical re-intervention or predispose patients to developing infections, pains or feeling of mass. This could lead to long hospital stay. Scrotal tamponade by bandaging or wearing of tight pants and elevation are practiced to reduce bleeding and haematoma formation. These methods require prolong use. Closed suction drains are scarcely used in resource-deprived communities due to high cost and non-availability.
AIM
This study was to determine the effectiveness of a closed non-suction drain in preventing scrotal collection requiring further surgical intervention and the predisposition to developing surgical site infection following nylon darn repair of inguinoscrotal hernia.
METHODS
Forty (40) participants were recruited for a preliminary study and assigned into control and interventional groups (CG, IG) for purposes of inserting flexible feeding tube (FFT) wound drain after nylon darn (ND) repair. Daily measurement of drained scrotal collection was carried out in the IG till the day drainage was zero. Residual volumes in IG and wound collection in the CG who were not candidates for re-intervention were determined at 14th and 28th post-operative days using ultrasound scan. Data were analyzed using SPSS version 25.
RESULTS
Three (3) patients (15.8%) in the CG required re-intervention. Surgical site infection rates for the CG and IG were, respectively, 2/19 versus 0/21 (ρ = 0.134).There was a numerical significant difference in the mean volumes of scrotal collections between the control (0.95 ± 0.42 ml) and the intervention group (0.44 ± 0.33 ml) [p value of 0.041] but with no clinical impact.
CONCLUSION
Simple inexpensive flexible feeding tube placement significantly reduced scrotal collection which forms a base for larger sample size in subsequent studies. This could reduce the feared risk of re-intervention, wound infection and long hospital stay post-operative. | 10.1007/s10029-021-02430-8 |
pubmed_31_20267 | This study was designed based on the hypothesis that changes in both the levels and surface marker expression of extracellular vesicles (EVs) isolated from the cerebrospinal fluid (CSF) may be associated with the clinical form, disease activity, and severity of multiple sclerosis (MS). The analyzes were performed on subjects affected by MS or other neurological disorders. EVs, which were isolated by ultracentrifugation of CSF samples, were characterized by flow cytometry. A panel of fluorescent antibodies was used to identify the EV origin: CD4, CCR3, CCR5, CD19, and CD200, as well as isolectin IB4. The Mann-Whitney U-test and Kruskal-Wallis test were used for statistical analyzes. EVs isolated from the CSF were more abundant in patients with progressive MS and in those with a clinically isolated syndrome than in all the other groups examined. Furthermore, an important change in the number of EVs and in their surface marker expression occurred during active phases of MS [i.e., clinical relapses and the presence of enhancing lesions on magnetic resonance imaging (MRI)]. In particular, the number of CSF-EVs increased in patients affected by MS during clinical relapse; this finding was associated with a decrease in the number of CD19+/CD200+ (naïve B cells) EVs. These markers are expressed by immature and naïve B lymphocytes, and to the best of our knowledge, this double staining has never been associated with MS, but their reduction has been observed in patients with another type of Th1 cell-mediated autoimmune disease. In contrast, the presence of lesions in the brain and spine on gadolinium-enhanced MRI was associated with an increase in the numbers of CCR3+/CCR5+ (subset of CD8 memory T cells), CD4+/CCR3+ (Th2 cells), and CD4+/CCR5+ (Th1 cells) CSF-EVs. Two points are worth emphasizing: (i) the data obtained in this study confirm that CSF-EVs represent a potentially promising tool to identify biomarkers specific for different phases of MS; and (ii) Considering the role of EVs in intercellular communication, our results provide some insights that improve our understanding of the relationships among some of the cell types that are mainly involved in MS pathogenesis (e.g., lymphocytes, glia, and neurons). | 10.3389/fncel.2018.00418 |
pubmed_278_23035 | AIMS
Adherence to medical therapy following acute coronary syndrome (ACS) affects a patient's prognosis. In this cohort study, we sought to assess the factors that could affect a patient's adherence to therapy after ACS.
METHODS
We prospectively collected information from patients (N = 964) hospitalized at the coronary care unit of the Federico II University Hospital, from 1 January 2015 to 30 June 2017, for ACS. Adherence to three classes of drugs including statins, antiplatelets [dual or single antiplatelet agent (SAPT)] and angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACE-I/ARB) and their composites were assessed at 1 month, 1 and 2 years after discharge.
RESULTS
At 30 days adherence to prescribed therapy was 94.4% for dual antiplatelet therapy (DAPT), 78.2% for statins, 92.7% for ACE-I/ARB and 70.7% for multitherapy. At 1 year, it was 91.1% for DAPT, 81.2% for ACE-I/ARB, 84.9% for statins and 71.4% for multitherapy. At 2 years, it was 97.1% for SAPT, 78.1% for ACE-I/ARB, 91.8% for statins, 72.8% for multitherapy. Multivariable logistic analysis demonstrated that at each time point, a telephone follow-up assessment predicts nonadherence to multitherapy and that a percutaneous coronary intervention at the index hospitalization is an independent predictor of adherence to composite therapy at 1 month and 1 year.
CONCLUSION
Up to 2 years after ACS, three out of four patients are adherent to multitherapy prescription; percutaneous coronary intervention during the index hospitalization improves a patient's adherence, whereas telephone follow-up is associated with reduced adherence to multitherapy.Campania Salute Network Registry (Clinical Trials.gov Identifier: NCT02211365). | 10.2459/JCM.0000000000001201 |
pubmed_980_2272 | Early introduction of appropriate antibiotherapy is one of the major prognostic-modifying factors in community acquired pneumonia (CAP). Despite established guidelines for empirical therapy, several factors may influence etiology and, consequently, antibiotic choices. The aims of this study were to analyze the etiology of CAP in adults admitted to a northern Portugal University Hospital and evaluate the yield of the different methods used to reach an etiological diagnosis, as well as analyze of the impact of patient demographic and clinical features on CAP etiology. We retrospectively analyzed 1901 cases of CAP with hospitalization. The diagnostic performance increased significantly when blood and sputum cultures were combined with urinary antigen tests. The most frequent etiological agent was Streptococcus pneumoniae (45.7%), except in August, when it was overtaken by gram-negative bacilli (GNB) and Legionella pneumophila infections. Viral infections were almost exclusive to winter and spring. A negative microbiological result was associated with increasing age, non-smoking and lack of both blood/sputum cultures. Younger age was a predictor for S. pneumoniae, Influenza and L. pneumophila infections. Active smoking without any previously known respiratory disease was a risk factor for legionellosis. COPD was associated with Haemophilus influenzae cases, while dementia was typical in GNB and S. aureus patients. Diabetes mellitus (DM) and heart disease were negative predictors of S. pneumoniae and H. influenzae, respectively. P. aeruginosa was an independent risk factor for mortality (OR 13.02, 95% CI 2.94-57.7). This study highlights the importance of a comprehensive microbiological diagnostic workup and provides clues to predicting the most probable CAP causative agents, based on a patient's clinical profile. These may be taken into account when establishing first line antibiotherapy. | 10.1016/j.pulmoe.2020.11.003 |
pubmed_959_492 | Although stress is a strong risk factor for poor health, especially for women, it remains unclear how stress affects the key neurohormones cortisol and oxytocin, which influence stress-related risk and resilience. Whereas cortisol mediates energy mobilization during stress, oxytocin has anti-inflammatory, anxiolytic, and analgesic effects that support social connection and survival across the lifespan. However, how these neurohormones interrelate and are associated with cognitive control of emotional information during stress remains unclear. To address these issues, we recruited 37 college-aged women (Mage = 19.19, SD = 1.58) and randomly assigned each to a one-hour experimental session consisting of either an acute stress (emotionally stressful video) or control (non-stressful video) condition in a cross-sectional manner across the semester. Salivary cortisol and oxytocin samples were collected at baseline and after the video, at which point participants also completed measures assessing affect and an emotional Stroop task. As hypothesized, the emotional stressor induced negative emotions that were associated with significant elevations in cortisol and faster Stroop reaction times. Moreover, higher baseline oxytocin predicted greater positive affect after the stressor and also better cognitive accuracy on the Stroop. Analyses examining the naturalistic stress effects revealed that basal oxytocin levels rose steeply three weeks before the semester's end, followed by rising cortisol levels one week later, with both neurohormones remaining elevated through the very stressful final exam period. Considered together, these data suggest that women's collective experiences of stress may be potentially buffered by a synchronous oxytocin surge that enhances cognitive accuracy and reduces stress "when the going gets tough". | 10.1080/10253890.2021.1876658 |
pubmed_881_10680 | 1. The time constants of motor and sensory nerve fibres were studied in normal human ulnar nerves by the method of latent addition, using threshold tracking to follow the recovery of excitability after brief conditioning current pulses. The 60 microseconds test and conditioning stimuli were applied at the wrist, and the conditioning stimuli were set to 90, 60, 30, -30, -60 and -90% of the control threshold current. Compound muscle action potentials were recorded from abductor digiti minimi, and sensory nerve action potentials from the little finger. 2. Recovery from depolarizing conditioning pulses was slower than recovery from hyperpolarizing pulses and strongly dependent on conditioning pulse amplitude. The voltage dependence of latent addition was attributed to subthreshold activation of sodium channels (local response). 3. Motor and sensory nerve excitability generally recovered from -90% hyperpolarizing pulses as the sum of two exponential components, although the slow component was negligible in some motor nerves. The fast component (time constant 43.3 +/- 2.0 microseconds, mean +/- S.E.M., n = 9) was similar between motor and sensory fibres in the same subject. It showed no consistent voltage dependence, and was attributed to a passive input time constant of the fibres. The slow component of recovery from hyperpolarizing pulses was greater in sensory than in motor fibres and was voltage dependent: it could be greatly increased in motor and sensory fibres by steady depolarization. It was attributed to a regenerative membrane current, active at the resting potential in sensory and at least some motor nerves. 4. The latent addition responses were compared with the computed responses of four theoretical models. Both motor and sensory responses were well fitted by a model in which a fraction of the sodium channels (less in motor than in sensory fibres) were activated at potentials 20 mV more negative than normal and at half the normal rate, and did not inactivate. 5. It is concluded that the differences in latent addition between motor and sensory fibres are primarily due to differences in non-classical, voltage-dependent ion channels, active close to the resting potential. These "threshold channels' may help to account for the longer strength-duration time constant of sensory fibres, for their lower rheobase, and for their greater tendency to fire repetitively. | 10.1113/jphysiol.1997.sp021857 |
pubmed_563_8723 | Background
Suboptimal neonatal circumcision analgesia causes a significant stress response. There is continued search for more effective analgesia for neonatal circumcision. We aimed to determine whether lidocaine-prilocaine cream (LPC) prior to dorsal penile nerve block (DPNB) offers better analgesia than DPNB alone.
Methods
A prospective randomized study of 72 neonates undergoing plastibell circumcision was randomized into two groups of 36 each. Group I received DPNB alone with 4 mg/kg plain lidocaine. Group II had 1 g LPC applied to the phallus 1 hour before DPNB. Serum cortisol levels were measured 30 min preoperatively and 30 min postoperatively. Heart rate (HR) and peripheral arterial oxygen saturation (SpO2) were noted at 30 min preoperatively, after DPNB injection, after excising the prepuce, and at 30 min thereafter. The primary outcome measure was change in serum cortisol levels, while secondary outcomes were changes in HR and SpO2.
Results
Both groups had increased mean serum cortisol levels, decreased mean SpO2 and increased mean HR from baseline. The rise in mean serum cortisol level was significantly lower in group II (8.09±4.53 µg/dL) than that in group I (11.42±7.83 µg/dL) (p=0.034). Changes in SpO2 and HR were significantly less in group II than that in group I patients (p<0.05), except for HR changes at 30 min after excision of the prepuce (p=0.086).
Conclusion
These data suggest that neonates who received LPC prior to DPNB experienced significantly less pain from plastibell circumcision than those who had DPNB alone.
Trial registration number
PACTR201906554747665. | 10.1136/wjps-2022-000470 |
pubmed_983_9734 | AIMS
We compared, in New Zealand Māori at risk of type 2 diabetes, advice emphasizing fiber rich carbohydrate and fat reduction (HCHF) and a high protein (HP) diet incorporating food preferences of indigenous people, with a control group (CONT).
METHODS
Eighty-four participants were randomized to three groups. Consecutive 8 week periods of supervised weight loss, supervised weight maintenance and unsupervised adherence to the prescribed diet using culturally sensitive methods were employed in intervention groups. Dietary compliance, body composition, blood pressure and metabolic variables were measured.
RESULTS
Body weight was reduced throughout on HP -2.6 (95% confidence interval: -4.4, -0.8)kg and HCHF (-1.6 (-3.0, -0.3)kg) compared with CONT. Total body fat (-1.6 (-3.0, -0.3)kg) and waist circumference (-3.0 (-5.7, -0.2)cm) showed sustained decreases on HP compared with CONT. Diet records suggested reasonable compliance with dietary advice on HP. Carbohydrate intake, but not dietary fiber, increased at the expense of fat on HCHF.
CONCLUSIONS
While moderate weight loss occurred on both HP and HCHF, HP was associated with some further favorable differences compared with the control group. | 10.1016/j.diabres.2011.11.021 |
pubmed_608_6981 | Hashing has attracted increasing research attention in recent years due to its high efficiency of computation and storage in image retrieval. Recent works have demonstrated the superiority of simultaneous feature representations and hash functions learning with deep neural networks. However, most existing deep hashing methods directly learn the hash functions by encoding the global semantic information, while ignoring the local spatial information of images. The loss of local spatial structure makes the performance bottleneck of hash functions, therefore limiting its application for accurate similarity retrieval. In this paper, we propose a novel deep ordinal hashing (DOH) method, which learns ordinal representations to generate ranking-based hash codes by leveraging the ranking structure of feature space from both local and global views. In particular, to effectively build the ranking structure, we propose to learn the rank correlation space by exploiting the local spatial information from fully convolutional network and the global semantic information from the convolutional neural network simultaneously. More specifically, an effective spatial attention model is designed to capture the local spatial information by selectively learning well-specified locations closely related to target objects. In such hashing framework, the local spatial and global semantic nature of images is captured in an end-to-end ranking-to-hashing manner. Experimental results conducted on three widely used datasets demonstrate that the proposed DOH method significantly outperforms the state-of-the-art hashing methods. | 10.1109/TIP.2018.2883522 |
pubmed_561_18341 | Human colorectal neuroendocrine cell carcinoma ( NECC ) is uncommon. Treatment of the disease has not yet been established, and NECC of the colon and rectum behave clinically more aggressively than their exocrine counterparts, so the prognosis is generally worse. One reason for the lack of established treatment is that there are no model systems of this disease. There have been a few reports on cell lines from neuroendocrine tumors, because these tumors are difficult to culture, and there are even fewer reports on colorectal carcinoma cell lines with neuroendocrine features. We therefore attempted to establish a permanent cell line in order to investigate the biological behavior and treatment of NECC. The cell line we succeeded in culturing is called N-TAK1. Gastrin promotes the growth of gastrointestinal epithelial cells and also stimulates the growth of gastrointestinal cancers. Hormone-receptor antagonists restrict the growth of hormone-dependent tumors. The growth of colon cancer was promoted by the application of gastrin, whereas it was restricted by proglumide, which is known to be a gastrin receptor antagonist. We demonstrated that gastrin has a stimulatory effect on the growth of N-TAK1 cells and that it could be detected by immunohistochemistry in the cells. We also showed that proglumide inhibited the growth effect of gastrin. | pubmed_561_18341 |
pubmed_491_12775 | Necrotic cells passively release HMGB1, which can stimulate TLR4 in an autocrine fashion to potentially initiate "sterile" inflammation that maintains different disease states. We have shown that prooxidants can induce NF-κB activation through TLR4 stimulation. We examined whether prooxidants enhance HMGB1-induced TLR4 signaling through NF-κB activation. We used LPS-EK as a specific agonist for TLR4, and PPC and SIN-1 as in situ sources for ROS. As model systems, we used HEK-Blue cells (stably transfected with mouse TLR4), RAW-Blue™ cells (derived from murine RAW 264.7 macrophages) and primary murine macrophages from TLR4-KO mice. Both HEK-Blue and RAW-Blue 264.7 cells express optimized secreted embryonic alkaline phosphatase (SEAP) reporter under the control of a promoter inducible by NF-κB. We treated cells with HMGB1 alone and/or in conjunction with prooxidants and/or inhibitors using SEAP release as a measure of TLR4 stimulation. HMGB1 alone and/or in conjunction with prooxidants increased TNFα and IL-6 released from TLR4-WT, but not from TLR4-KO macrophages. Pro-oxidants increased HMGB1 release, which we quantified by ELISA. We used both fluorescence microscopy imaging and flow cytometry to quantify the expression of intracellular ROS. TLR4-neutralizing antibody decreased prooxidant-induced HMGB1 release. Prooxidants promoted HMGB1-induced NF-κB activation as determined by increased release of SEAP and TNF-α, and accumulation of iROS. HMGB1 (Box A), anti-HMGB1 and anti-TLR4-neutralizing pAbs inhibited HMGB1-induced NF-κB activation, but HMGB1 (Box A) and anti-HMGB1 pAb had no effect on prooxidant-induced SEAP release. The present results confirm that prooxidants enhance proinflammatory effects of HMGB1 by activating NF-κB through TLR4 signaling. | pubmed_491_12775 |
pubmed_236_9091 | Periodontitis affects a limited number of susceptible humans. The aim of this study was to determine whether there is a difference in the inflammatory reaction between patients with gingivitis and those with periodontitis. For this purpose the levels of elastase and lactoferrin were measured in gingival crevicular fluid (GCF) from three types of sites: i) inflamed sites in patients with gingivitis alone, inflamed sites both ii) with and iii) without tissue destruction in patients with periodontitis. Elastase activity, measured with a chromogenic substrate was significantly higher in the two types of sites in periodontitis patients. Lactoferrin levels, measured with ELISA were the same in the three types of sites. In vitro activation of granulocytes from healthy volunteers with Fc-receptor stimulation showed that the entire release of lactoferrin occurred immediately. In contrast, elastase release was time-dependent and continued throughout the experiment. Thus, the degranulation of the specific (lactoferrin) and azurophil granule (elastase) are under separate control and the two parameters can be combined in a ratio in order to characterize the granulocytes of a given patient. Assuming an immediate release of lactoferrin from the activated granulocytes in vivo, similar amounts of lactoferrin in the three types of sites can be regarded as reflecting similar numbers of granulocytes in the three types of sites. Consequently, a higher elastase activity in GCF from patients with periodontitis indicates a higher rate of release from the cells per se and a granulocyte-associated specific host response. | 10.1111/j.1600-0765.1994.tb01222.x |
pubmed_468_14728 | Recent progress in research on Fe(3)O(4) nanocrystals has attracted much attention both for investigating fundamental nanomagnetism and their potential applications in nanocatalysis, biosensing, magnetic resonance imaging (MRI) contrast agents and drug delivery. In this feature article, we provide an overview of synthetic strategies and growth mechanisms of various Fe(3)O(4) nanostructures, discuss the uniqueness of associated properties, and illustrate their potential applications. | 10.1039/c0cc05862a |
pubmed_667_7014 | UNLABELLED
Gram-positive bacteria, notably coagulase negative staphylococci, have become an important cause of infection in neonates. Furthermore, many of these pathogens are now resistant to multiple antibacterial agents. Teicoplanin, a glycopeptide antibiotic, is active against a broad range of Gram-positive pathogens, including methicillin-resistant staphylococci. It has advantages over vancomycin in terms of tolerability, with a lower propensity to cause nephrotoxicity and anaphylactoid-like reactions, and in terms of ease of administration and monitoring requirements. The clinical utility of teicoplanin in neonates with Gram-positive infections has been investigated in several noncomparative studies. Clinical and bacteriological response rates in 173 neonates treated with teicoplanin 8-10 mg/kg intravenously or intramuscularly once daily after a loading-dose regimen of 10-20 mg/kg per day have ranged from 80%-100% and 83%-100%, respectively. Few adverse events related to teicoplanin have been reported in this patient population.
CONCLUSION
Teicoplanin (8-10 mg/kg) administered intravenously or intramuscularly once daily after a loading-dose regimen of 15-20 mg/kg per day appears to be an effective and well tolerated treatment for Gram-positive infections in neonates. | 10.1007/s004310050629 |
pubmed_495_19818 | The outcome of 38 beta-blocker users (group BB, 28 men and 10 women with a mean age of 56 +/- 4 years) was compared to that of 100 non-users (group NU, 69 men and 31 women with a mean age of 57 +/- 8 years) after acute myocardial infarction (AMI). The two groups were compared in terms of electrocardiographic (EKG) location of the AMI (anterior, inferior and lateral), EKG Q and non-Q wave infarction, clinical functional class of Forrester, serum creatine phosphokinase MB fraction (CKMB) peak release and intrahospital mortality. There were no differences between groups concerning sex or severity of coronary artery disease but arterial hypertension was 2-fold more prevalent in group BB. The EKG location of the AMI was similar in the two groups. Non-Q infarction was significantly more prevalent in group BB (37%) than in group NU (6%). The incidence of clinical functional class IV of Forrester and the serum CKMB peaks were significantly lower in group BB (2.6% vs 16.0% and 53 +/- 3 vs 68 +/- 9 IU/l, respectively). Intrahospital mortality was also significantly lower in group BB (2.6%) than in group NU (10%). These data suggest the beneficial effect of previous long-term use of beta-blockers as indicated by a lower incidence of cardiogenic shock and a significant decrease in intrahospital mortality after AMI. | pubmed_495_19818 |
pubmed_128_18623 | To successfully navigate in the hearing world, deaf individuals must be able to read and write to bridge the gap when others do not know American Sign Language. Unfortunately, 90% of deaf children are born to hearing parents and do not develop language skills early on, which negatively impacts their ability to access health information and healthcare. Healthcare providers must ensure they provide culturally competent care and their practices accommodate the needs of deaf patients to mitigate communication barriers and ensure equitable care with positive health outcomes. | 10.1097/01.NPR.0000445956.21045.c4 |
pubmed_994_7148 | BACKGROUND
Price setting and reimbursement decisions regarding drugs are competence of individual member states in Europe. These decisions involve important trade-offs between social, ethical, clinical and economic criteria. The aim of this study was to investigate the relative importance of criteria for reimbursement of oncology drugs in Belgium.
METHODS
Reimbursement dossiers on oncology drugs for which reimbursement was applied between 2002 and 2013 were consulted. Multivariate logistic regression was performed.
RESULTS
Results showed that clinical evidence and presence of alternative treatments have a significant impact on the reimbursement decisions.
CONCLUSIONS
Evidence-based medicine still plays a role in Belgian reimbursement decision-making. In order to allow transition towards value-based medicine and avoid spending money on products with limited incremental benefit, therapeutic need at patient level need to be taken into account. | 10.1586/14737167.2015.1047347 |
pubmed_308_19305 | OBJECTIVES
We compared the diagnostic performance of off-site evaluation between prospectively obtained 3D and 2D ultrasound for thyroid nodules.
METHODS
3D and 2D ultrasonographies were preoperatively obtained from 85 consecutive patients (mean age, 51 years; age range, 28-83 years) who were referred for a total thyroidectomy. Three radiologists independently evaluated 3D and 2D images of 91 pathologically confirmed thyroid nodules (30 benign and 61 malignant nodules) for nodule characterization. Diagnostic performance, interobserver agreement and time for scanning were compared between 3D and 2D.
RESULTS
3D had significantly higher sensitivities than 2D for predicting malignancy (78.7 % vs. 61.2 %, P < 0.01) and extrathyroidal extension (66.7 % vs. 46.4 %, P = 0.03) in malignancy. In terms of specificities, there were no statistically significant differences between 2D and 3D for predicting malignancy (78.4 % vs. 74.8 %, P = 1.00) and extrathyroidal extension (63.6 % vs. 57.6 %, P = 0.46). With respect to interobserver agreement, 3D showed moderate agreement (κ = 0.53) for predicting extrathyroidal extension in malignancy compared with 2D ultrasound, which showed fair agreement (κ = 0.37). 3D saved time (30 ± 56.52 s) for scanning compared with 2D.
CONCLUSION
For off-site evaluation, 3D US is more useful for diagnosis of thyroid nodules than 2D US.
KEY POINTS
• 3D had higher sensitivity than 2D for predicting malignancy and extrathyroidal extension. • 3D showed better agreement for predicting extrathyroidal extension in malignancy than 2D. • 3D thyroid ultrasound saved time for scanning compared with 2D. • For off-site evaluation of thyroid nodules, 3D is more useful than 2D. | 10.1007/s00330-015-4193-2 |
pubmed_182_12308 | B cells develop high affinity receptors during the course of affinity maturation, a cyclic process of mutation and selection. At the end of affinity maturation, a number of cells sharing the same ancestor (i.e. in the same "clonal family") are released from the germinal center; their amino acid frequency profile reflects the allowed and disallowed substitutions at each position. These clonal-family-specific frequency profiles, called "substitution profiles", are useful for studying the course of affinity maturation as well as for antibody engineering purposes. However, most often only a single sequence is recovered from each clonal family in a sequencing experiment, making it impossible to construct a clonal-family-specific substitution profile. Given the public release of many high-quality large B cell receptor datasets, one may ask whether it is possible to use such data in a prediction model for clonal-family-specific substitution profiles. In this paper, we present the method "Substitution Profiles Using Related Families" (SPURF), a penalized tensor regression framework that integrates information from a rich assemblage of datasets to predict the clonal-family-specific substitution profile for any single input sequence. Using this framework, we show that substitution profiles from similar clonal families can be leveraged together with simulated substitution profiles and germline gene sequence information to improve prediction. We fit this model on a large public dataset and validate the robustness of our approach on two external datasets. Furthermore, we provide a command-line tool in an open-source software package (https://github.com/krdav/SPURF) implementing these ideas and providing easy prediction using our pre-fit models. | 10.1371/journal.pcbi.1006388 |
pubmed_582_14241 | OBJECTIVE
After hip fracture, muscle strength and power remain persistently poor, especially in the fractured leg. This study explores whether asymmetrical leg extension power (LEP) deficit affects mobility in women after proximal femoral fracture (PFF).
DESIGN
In this observational study, LEP of both legs, 10- and 50-foot walking speed, and stair-climbing speed were measured in 43 women, aged 73-96, at 1 and 13 wks after surgical repair of PFF. Asymmetrical LEP deficit was calculated as (fractured/(sum both legs)) x 100%.
RESULTS
Between weeks 1 and 13 after PFF surgery, LEP increased in the fractured and nonfractured legs by 100% and 30%, respectively. Asymmetrical deficit was reduced from 28.5 +/- 10.2% to 40.4 +/- 8.6%. Linear regression analyses showed that poorer LEP of the nonfractured leg at week 1 correlated significantly with slower walking (beta > 0.525, P < 0.001) and stair-climbing speed (beta > 0.349, P < 0.016) and predicted poorer mobility 12 wks later (beta > 0.354, P < 0.020). Large asymmetrical LEP deficit was cross-sectionally associated with slow stair-climbing speed (beta > 0.343, P < 0.018) at weeks 1 and 13, but not with walking speed.
CONCLUSIONS
Higher LEP of the nonfractured leg predicted better recovery of mobility after PFF. Larger asymmetrical LEP deficit correlated with limitation in climbing stairs-a more challenging mobility task where fluent performance requires unilateral force production. | 10.1097/PHM.0b013e318164a9e2 |
pubmed_58_6179 | BACKGROUND
The diagnosis of myocarditis presenting as isolated acute chest pain with elevated troponins but normal systolic function is challenging with significant drawbacks even for the gold-standard endomyocardial biopsy.
OBJECTIVE
This study aimed to evaluate the diagnostic role of strain imaging by echocardiography and cardiac MRI in these patients.
MATERIALS AND METHODS
This was a retrospective review of children with cardiac MRI for acute chest pain with elevated troponins compared to normal controls. Echocardiographic fractional shortening, ejection fraction, speckle-tracking-derived peak longitudinal, radial, and circumferential strain were compared to cardiac MRI ejection fraction, T2 imaging, late gadolinium enhancement, speckle-tracking-derived peak longitudinal strain, radial strain, and circumferential strain.
RESULTS
Group 1 included 10 subjects diagnosed with myocarditis, 9 (90%) males with a median age of 15.5 years (range: 14-17 years) compared with 10 age-matched controls in group 2. All subjects in group 1 had late gadolinium enhancement consistent with myocarditis and troponin ranged from 2.5 to >30 ng/ml. Electrocardiogram changes included ST segment elevation in 6 and abnormal Q waves in 1. Qualitative echocardiographic function was normal in both groups and mean fractional shortening was similar (35±6% in group 1 vs. 34±4% in group 2, P=0.70). Left ventricle ejection fraction by cardiac MRI, however, was lower in group 1 (52±9%) compared to group 2 at (59±4%) (P=0.03). Cardiac MRI derived strain was lower in group 1 vs. group 2 for speckle-tracking-derived peak longitudinal strain (-12.8±2.8% vs. -17.1±1.5%, P=0.001), circumferential strain (-12.3±3.8% vs. -15.8±1.2%, P=0.020) and radial strain (13.6±3.7% vs. 17.2±3.2%, P=0.040). Echocardiography derived strain was also lower in group 1 vs. group 2 for speckle-tracking-derived peak longitudinal strain (-15.6±3.9% vs. -20.8±2.2%, P<0.002), circumferential strain (-16±3% vs. -19.8±1.9%, P<0.003) and radial strain (17.3±6.1% vs. 24.8±6.3%, P=0.010).
CONCLUSION
In previously asymptomatic children, myocarditis can present with symptoms of acute chest pain suspicious for coronary ischemia. Cardiac MRI and echocardiographic strain imaging are noninvasive, radiation-free tests of immense diagnostic utility in these situations. Long-term studies are needed to assess prognostic significance of these findings. | 10.1007/s00247-017-4061-0 |
pubmed_1135_23209 | OBJECTIVE
We present a survey of sex differences and socio-demographic and clinical variables in children and adolescents receiving a psychiatric consultation service in an emergency department (ED).
METHODS
This observational, retrospective, and cross-sectional study included all records of patients (age, <18 years) who received psychiatric services in an ED in a 4-year period (January 2010 to December 2013).
RESULTS
Two hundred fifty-nine records of children and adolescents were located. The mean age of the participants was 14.19 years, and most subjects were female (59.5%) and had private health insurance (83.7%). Most participants (87.4%) were accompanied by their parents. The main complaints were suicide attempts (21.8%) and psychomotor agitation/aggressiveness (21.8%). Unipolar depression (37.8%) and adjustment, reactive, and anxiety disorders (13.7%) were the most prevalent diagnoses. Most patients received an indication of psychiatric hospitalization (51.7%). Females had more suicide attempts than males (28.3% vs 12.4%) and less psychomotor agitation/aggressiveness than males (15.5% vs 31.4%). Females also exhibited more unipolar depression (47.6% vs 23.5%), fewer psychotic disorders (4.2% vs 16.3%), and substance use/misuse (1.4% vs 13.3%) than males. Males needed more psychiatric medication during evaluation (37.9% vs 19.2%).
CONCLUSIONS
This survey of the profile of pediatric patients evaluated by a psychiatric service in an ED in Brazil was the first of its kind. The large percentage of patients referred for hospitalization highlights the importance of specialized psychiatry care for this age group in this facility, which is a common entry point for mental health care. | 10.1097/PEC.0000000000000505 |
pubmed_248_12036 | UNLABELLED
Investigators conducting studies of the molecular genetics of complex traits in humans often need rationally to select a set of single nucleotide polymorphisms (SNPs) from the hundreds or thousands available for a candidate gene. Accomplishing this requires integration of genomic data from distributed databases and is both time-consuming and error-prone. We developed the TAMAL (Technology And Money Are Limiting) web site to help identify promising SNPs for further investigation. For a given list of genes, TAMAL identifies SNPs that meet user-specified criteria (e.g. haplotype tagging SNPs or SNP predicted to lead to amino acid changes) from current versions of online resources (i.e. HapMap, Perlegen, Affymetrix, dbSNP and the UCSC genome browser).
AVAILABILITY
TAMAL is a platform independent web-based application available free of charge at http://neoref.ils.unc.edu/tamal.
SUPPLEMENTARY INFORMATION
http://neoref.ils.unc.edu/tamal/. | 10.1093/bioinformatics/btk025 |
pubmed_5_13354 | Clinical outcomes measure patient health or well-being. The choice of an outcome measure for use in a clinical trial or study is complex. It is even more difficult when no appropriate outcome measure exists, necessitating the development of a novel one. The ideal clinical outcome should be credible, comprehensive, sensitive to change, accurate, biologically sensible, and feasible. This paper describes the attributes of clinical outcomes and illustrates how to develop novel outcomes, using as an example the authors' experience in developing a wound cosmesis outcome measure. | 10.1111/j.1553-2712.2000.tb02249.x |
pubmed_694_5289 | Interleukin-1beta(IL-1beta) and tumour necrosis factor-alpha (TNF-alpha) are potent bone resorbing cytokines that may contribute to the development of the osteolytic bone disease observed in patients with multiple myeloma (MM). Although these factors have been identified in cultures of bone marrow mononuclear cells isolated from patients, the identity of the cells responsible for producing IL-1beta and TNFalpha remains unclear. Using a sensitive dual-colour fluorescence in situ hybridization (FISH) technique and a two-colour immunofluorescence method we have investigated the expression of the mRNA and protein, for IL-1beta and TNFalpha, by individual bone marrow plasma cells from patients with MM and monoclonal gammopathy of undetermined significance (MGUS). The mRNA for IL-1beta and TNFalpha was identified in all cells expressing the immunoglobulin light chain from all patients with MM and MGUS. However, the IL-1beta protein could not be detected in cytoplasmic light chain positive cells in any of the patients examined. In contrast, the TNFalpha protein was detected in clonal plasma cells from patients with both MM and MGUS. Interestingly, the IL-1beta and TNFalpha mRNA and proteins were readily detected within a small proportion of the non-plasma cells from patients with both MM and MGUS. These data suggest that myeloma cells in vivo are able to produce TNFalpha but not IL-1beta. In addition, a small proportion of accessory cells are likely to be able to contribute to the production of both ILbeta and TNFalpha. | 10.1046/j.1365-2141.1999.01193.x |
pubmed_787_19093 | PURPOSE
Clear and complete communication between health care providers is a prerequisite for safe patient management and is a major priority of the Joint Commission's 2008 National Patient Safety Goals. The goal of this study was to describe nurses' perceptions of nurse-physician communication in the long-term care (LTC) setting.
METHODS
Mixed-method study including a self-administered questionnaire and qualitative semistructured telephone interviews of licensed nurses from 26 LTC facilities in Connecticut. The questionnaire measured perceived openness to communication, mutual understanding, language comprehension, frustration, professional respect, nurse preparedness, time burden, and logistical barriers. Qualitative interviews focused on identifying barriers to effective nurse-physician communication that may not have previously been considered and eliciting nurses' recommendations for overcoming those barriers.
RESULTS
Three hundred seventy-five nurses completed the questionnaire, and 21 nurses completed qualitative interviews. Nurses identified several barriers to effective nurse-physician communication: lack of physician openness to communication, logistic challenges, lack of professionalism, and language barriers. Feeling hurried by the physician was the most frequent barrier (28%), followed by finding a quiet place to call (25%), and difficulty reaching the physician (21%). In qualitative interviews, there was consensus that nurses needed to be brief and prepared with relevant clinical information when communicating with physicians and that physicians needed to be more open to listening.
CONCLUSIONS
A combination of nurse and physician behaviors contributes to ineffective communication in the LTC setting. These findings have important implications for patient safety and support the development of structured communication interventions to improve quality of nurse-physician communication. | 10.1097/PTS.0b013e3181b53f9b |
pubmed_988_16233 | The developmental toxicity of 2,4-Pentanedione (2,4-PD; CAS No. 123-54-6), a widely used industrial chemical, was investigated by vapour exposure, because of its widespread use, and potential for human exposure. Timed-pregnant Fischer 344 rats were exposed on gestational days (gd) 6 to 15 inclusive to analytically measured concentrations (as mean +/- SD) of 53 +/- 1.6, 202 +/- 4.7 and 398 +/- 5.7 ppm 2,4-PD vapour. At sacrifice (gd 21) foetuses were examined for external, visceral and skeletal variations and malformations. There was no maternal mortality, and body weight was reduced only at 398 ppm. Histological examination of maternal brains from the 398 ppm group showed no abnormalities. No treatment-related effects were seen on number of corpora lutea; total, nonviable or viable implants per litter; pre-or post-implantation losses; or foetal sex ratio. Reduced foetal body weight per litter was seen at 398 ppm (males and females and all foetuses) and 202 ppm (males and all foetuses). There was no concentration-related, or statistically significant, increase in the incidence of individual malformations, malformations by category (external, visceral or skeletal), or total malformations. Partial foetal atelectasis was increased at 398 ppm, and the increased incidence of 17 skeletal variants (out of 79 observed) indicated a consistent pattern of foetotoxicity at 398 ppm. In summary, at 398 ppm there was maternal toxicity (reduced body weight) and foetotoxicity (reduced body weight and ossification) and at 202 ppm there was foetotoxicity (reduced body weight). Embryotoxicity or teratogenicity were not seen at any concentration. The no-observable-effects concentration was 53 ppm for both maternal and developmental toxicity. | 10.1177/074823379000600308 |
pubmed_857_17198 | The predictivity of raised plasma prolactin (PRL) concentrations in differentiating seizure from syncopal attack was prospectively assessed in all patients consecutively admitted to the Clinica Neurologica of Brescia, Italy in a 12-month period who fulfilled the criteria for either a seizure or syncopal attack. Postictal plasma prolactin concentration (P1) was assessed as soon as possible after the event. Three further assessments were performed: P2 was sampled 1 h after P1, P3, and P4 were sampled in the morning for the next 2 days. Patients who had had a seizure showed significantly increased P1 concentrations, when P1 was sampled within 60 min of the attack. In seizure patients assessed > 1 h after the event, P1 was not significantly different from either P2, P3, or P4. In patients who had had a syncopal attack, PRL concentration never increased. In patients assessed < or = 60 min after the seizure, cutoff criterion of P1 exceeding by +3 SD the mean calculated on P2, P3, and P4 yielded a positive predictive value of 89% and a negative predictive value of 61%. These findings confirm that plasma prolactin concentration is highly predictive of true epilepsy but barely predictive of pseudoseizures. | 10.1111/j.1528-1157.1993.tb02132.x |
pubmed_292_2509 | BACKGROUND
The use of mechanism of injury as a predictor of injury outcome presents practical challenges because this variable may be missing or inaccurate in many databases. The purpose of this study was to determine the importance of mechanism of injury as a predictor of mortality among injured children.
METHODS
The records of children (<15-y-old) sustaining a blunt injury were obtained from the National Trauma Data Bank. Models predicting injury mortality were developed using mechanism of injury and injury coding using either abbreviated injury scale post-dot values (low-dimensional injury coding) or injury International Classification of Diseases, Ninth Revision codes and their two-way interactions (high-dimensional injury coding). Model performance with and without inclusion of mechanism of injury was compared for both coding schemes, and the relative importance of mechanism of injury as a variable in each model type was evaluated.
RESULTS
Among 62,569 records, a mortality rate of 0.9% was observed. Inclusion of mechanism of injury improved model performance when using low-dimensional injury coding but was associated with no improvement when using high-dimensional injury coding. Mechanism of injury contributed to 28% of model variance when using low-dimensional injury coding and <1% when high-dimensional injury coding was used.
CONCLUSIONS
Although mechanism of injury may be an important predictor of injury mortality among children sustaining blunt trauma, its importance as a predictor of mortality depends on the approach used for injury coding. Mechanism of injury is not an essential predictor of outcome after injury when coding schemes are used that better characterize injuries sustained after blunt pediatric trauma. | pubmed_292_2509 |
pubmed_923_20089 | OBJECTIVE
To examine the clinical and epidemiologic features of hepatitis C virus (HCV) infection in a gastroenterology/hepatology practice in Ottawa.
DESIGN
Retrospective chart review.
PATIENTS
Sixty-three consecutive patients found to be anti-HCV positive. Their charts were analysed with respect to risk factors, history of hepatitis, serum aspartate aminotransferase (AST) levels and the presence of hepatitis B markers. The long-term sexual partners of 29 patients agreed to undergo HCV antibody testing.
RESULTS
Of the patients 48 (76%) had been exposed to HCV parenterally: 27 used intravenous drugs, and 21 had received blood or blood products. Eleven patients did not have any known risk factor (sporadic infection), but eight of them had lived in countries where hepatitis C may be more prevalent; the other three had locally acquired infection. The mean serum AST level at the first visit was 140 (normally less than 40) IU/L. At least one hepatitis B marker was identified in 33% of the patients. None of the sexual partners who were tested were anti-HCV positive.
CONCLUSION
Most cases of hepatitis C in Ottawa are acquired through parenteral exposure; sexual transmission is rare. Sporadic infection in the Ottawa region is rare but may be more common in people from countries with a higher prevalence rate of hepatitis C. Most cases of hepatitis C are asymptomatic. | pubmed_923_20089 |
pubmed_12_17180 | Plasma cortisol levels during abdominal surgery under sevoflurane anesthesia were evaluated in 22 patients who ranged in ages from 37 to 65. They underwent either gastrointestinal or gynecological abdominal surgery. Anesthesia was induced and maintained with sevoflurane (1-5%) in nitrous oxide (4 l.min-1) and oxygen (2 l.min-1). Succinylcholine was administered intravenously to facilitate tracheal intubation and pancuronium was given intravenously during surgery. Lactated Ringer's solution at a speed of 10-15 ml.kg-1.hr-1 was also administered intravenously throughout the surgical procedures. Plasma cortisol levels were unchanged with the induction of sevoflurane anesthesia alone, but they increased significantly 2-3 times of the preanesthetic levels during and after surgery in both groups. However, the concentrations of plasma cortisol after recovery from anesthesia were significantly higher in the gastrointestinal group than in the gynecological group. The findings suggest that plasma cortisol levels after surgery reflect the difference in magnitude of stress response between gastrointestinal and gynecological surgery. | pubmed_12_17180 |
pubmed_938_10512 | Enteral nutrition has proved to be the route of choice for delivery of dietary needs to patients with functioning gastrointestinal tracts. Because of the wide variety of available formulas, it is essential for nurses to be aware of the specific indications for each. In addition, the route of delivery and the type of tube selected can significantly affect the success of nutritional support. Nurses can and should play important roles in the design and implementation of successful enteral nutritional support. | pubmed_938_10512 |
pubmed_1088_22983 | In this study, we report the molecular structure of the breakpoint region in a new chromosomal translocation, t(2;7)(p24.3;p14.2), in a case of acute myeloid leukemia transformed from myelodysplastic syndrome (MDS). An extensive fluorescence in situ hybridization (FISH) analysis showed that NAG (2p24.3) and ELMO1 (7p14.2) were involved at the breakpoints of t(2;7)(p24.3;p14.2). Furthermore, we detected a novel chimeric transcript consisting of NAG and ELMO1. Interestingly, this transcript encoded a truncated molecular form of 3'ELMO1 as the result of a frameshift caused by the chromosomal translocation. Although this study does not provide direct evidence that a defect in NAG-ELMO1 plays a role in the pathogenesis or the leukemic change in MDS, it does suggest that defects in NAG-ELMO1 potentially contributed to the leukemic progression in this case. | 10.1038/jhg.2009.40 |
pubmed_604_6645 | Assisted reproductive technology (ART) for couples affected by HIV constitutes an important progress for public health. France has been the first country to offer this possibility on a national level, within the public health care system, with the best security and quality standards. This progress is, for one part, a consequence of the collaboration between community-based organizations representing HIV positive persons and their close relations, and pioneer medical teams in this field. This collaboration and this alliance have led to progressively convince the medical community and public health authorities concerned by the fight against aids of the usefulness of this care. Nevertheless, different obstacles have been encountered on the way between theory (decision of the Minister of Health, May 2001, allowing ART for couples affected by HIV), and practice. Medical teams often lack staff in sufficient number. Some doctors have, for reasons they qualify as ethical, refused to take HIV positive women into care. The opening of medical centers in areas where they are missing, particularly the French territories of America, remains a high priority. Last, the legal limits restricting access to ART in France deserve to be questioned. Community-based organizations and medical teams have been able to work as partners, sharing common goals of public health and quality of care. Nevertheless, among health institutions and national agencies in France, the consideration of the point of view of patients and their organizations is far from being a general rule, despite laws which clearly define patients' collective rights. We thank the Fédération française d'étude de la reproduction (FFER) and the journal Gynécologie Obstétrique & Fertilité for giving non-governmental organizations an opportunity to reaffirm our commitment to constructive common work. | 10.1016/j.gyobfe.2007.07.024 |
pubmed_982_14342 | Evidence exists that BRCA2 carriers may have an elevated risk of breast, ovarian, colon, prostate, and pancreatic cancer. In general, carriers are defined as individuals with protein truncating mutations within the BRCA2 gene. Many Brca2 knockout lines have been produced and characterized in the mouse. We previously produced a rat Brca2 knockout strain in which there is a nonsense mutation in exon 11 between BRC repeats 2 and 3, and a truncated protein is produced. Interestingly, while such a mutation in homozygous mice would lead to limited survival of approximately 3 months, the Brca2-/- rats are 100% viable and the vast majority live to over 1 year of age. Brca2-/- rats show a phenotype of growth inhibition and sterility in both sexes. Aspermatogenesis in the Brca2-/- rats is due to a failure of homologous chromosome synapsis. Long-term phenotypes include underdeveloped mammary glands, cataract formation and lifespan shortening due to the development of tumors and cancers in multiple organs. The establishment of the rat Brca2 knockout model provides a means to study the role of Brca2 in increasing cancer susceptibility and inducing a novel ocular phenotype not previously associated with this gene. | 10.1038/sj.onc.1209960 |
pubmed_358_15943 | A structural homology between the endogenous differentiation factor of the HL-60 cell line of promyelocyte leukemia (HLDF) and several DNA/RNA-binding and DNA/RNA-hydrolyzing proteins was revealed, and expression of the hldf gene in prokaryotic systems was studied. On the basis of these experiments, the amino acid sequence of an 8-membered fragment of HLDF with potential nuclease activity was identified. The synthetic octapeptide RRWHRLKE was shown to be capable of the cleavage of RNA, linear DNA from phage lambda, and all forms of plasmid DNA. We established that treatment of the HL-60 cell culture with this peptide (10(-6) M) results in an increase in the number of apoptotic cells and suggested that HLDF is involved in processes of apoptosis. | pubmed_358_15943 |
pubmed_117_14068 | Neuregulin-1 (NRG1) represents an important factor for multiple processes including neurodevelopment, brain functioning or cognitive functions. Evidence from animal research suggests an effect of NRG1 on the excitation-inhibition (E/I) balance in cortical circuits. However, direct evidence for the importance of NRG1 in E/I balance in humans is still lacking. In this work, we demonstrate the application of computational, biophysical network models to advance our understanding of the interaction between cortical activity observed in neuroimaging and the underlying neurobiology. We employed a biophysical neuronal model to simulate large-scale brain dynamics and to investigate the role of polymorphisms in the NRG1 gene (rs35753505, rs3924999) in n = 96 healthy adults. Our results show that G/G-carriers (rs3924999) exhibit a significant difference in global coupling (P = 0.048) and multiple parameters determining E/I-balance such as excitatory synaptic coupling (P = 0.047), local excitatory recurrence (P = 0.032) and inhibitory synaptic coupling (P = 0.028). This indicates that NRG1 may be related to excitatory recurrence or excitatory synaptic coupling potentially resulting in altered E/I-balance. Moreover, we suggest that computational modeling is a suitable tool to investigate specific biological mechanisms in health and disease. | 10.1093/cercor/bhaa339 |
pubmed_630_24251 | We describe cranial and mandibular remains of three undescribed individuals of the giant mustelid Megalictis ferox Matthew, 1907 from the latest Arikareean (Ar4), Early Miocene mammal fauna of Nebraska, and Wyoming (USA) housed at the American Museum of Natural History (New York, USA). Our phylogenetic hypothesis indicates that Ar4 specimens assigned to M. ferox constitute a monophyletic group. We assign three additional species previously referred to Paroligobunis to Megalictis: M. simplicidens, M. frazieri, and "M." petersoni. The node containing these four species of Megalictis and Oligobunis forms the Oligobuninae. We test the hypothesis that Oligobuninae (Megalictis and Oligobunis) is a stem mustelid taxon. Our results indicate that the Oligobuninae form the sister clade to the crown extant mustelids. Based on the cranium, M. ferox is a jaguar-size mustelid and the largest terrestrial mustelid known to have existed. This new material also sheds light on a new ecomorphological interpretation of M. ferox as a bone-crushing durophage (similar to hyenas), rather than a cat-like hypercarnivore, as had been previously described. The relative large size of M. ferox, together with a stout rostrum and mandible made it one of the more powerful predators of the Early Miocene of the Great Plains of North America. | 10.1371/journal.pone.0152430 |
pubmed_1131_21936 | Clinical and pre-clinical evidence has implicated neuregulin 1 (NRG1) as a critical component in the pathophysiology of schizophrenia. However, the arrival of the genome-wide association study (GWAS) era has yielded results that challenge the relevance of NRG1 in schizophrenia due to the absence of a genome-wide significant NRG1 variant associated with schizophrenia. To assess NRG1's relevance to schizophrenia in the GWAS era, we provide a targeted review of recent preclinical evidence on NRG1's role in regulating several aspects of excitatory/inhibitory neurotransmission and in turn schizophrenia risk. We also present a systematic review of the last decade of clinical research examining NRG1 in the context of schizophrenia. We include concise summaries of genotypic variation, gene-expression, protein expression, structural and functional neuroimaging as well as cognitive studies conducted during this time period. We conclude with recommendations for future clinical and preclinical work that we hope will help prioritize a strategy forward to further advance our understanding of the relationship between NRG1 and schizophrenia. | 10.1016/j.neubiorev.2016.06.001 |
pubmed_784_12619 | We evaluated the role of thallium-201 single-photon emission-computed tomography (SPECT) in diagnosis, differential diagnosis and follow-up of 33 patients with primary brain tumors. 27 of 33 lesions were detectable by Tl-201 SPECT because only two of eight low-grade (grade 1 and 2) astrocytomas showed Tl-201 accumulation up to a tumor to nontumor ratio of 2.6. High grade (grade 3 and 4) astrocytomas showed Tl-201 accumulation in the range of 2.2 up to 13.0 and were different from low-grade astrocytomas. Noninvasive grading of astrocytomas is therefore possible, whereas differential diagnosis of oligodendrogliomas and astrocytomas or meningiomas was not possible with Tl-201. In the follow-up of six patients, we could demonstrate, that tumor progression is correlated with increasing and tumor regression with decreasing Tl-201 accumulations. This functional changing proceed morphological findings in CT. But vanishing of Tl-201 accumulation during therapy does not mean vanishing of tumor as could be demonstrated by follow-up. | pubmed_784_12619 |
pubmed_780_530 | INTRODUCTION
Morbidity due to motor vehicle accidents was analysed in a descriptive study based on reports of hospitals with the objective to characterize their victims, types of injuries, and the health care provided.
METHODS
The study was carried out in two municipal hospitals of Rio de Janeiro, Brazil. Motor vehicle accidents were defined as a run over, a collision, and "other traffic accidents". Data was collected from cases seen in May (Hospital 1) and June (Hospital 2) of 1996 by 7 teams that alternated in shifts of 12 hours, covering the collection 24 hours per day. The events were classified according to the victim or, when it was impossible, to the person who helped them or accompanied them to the hospital.
RESULTS
In the study period, 320 cases were seen in Hospital 1 and 290 in Hospital 2. Most of the victims were men (69.3%) in both of hospitals and the most affected group was young adults between 20 to 39 years (60.5% in Hospital 1 and 47.5% in Hospital 2). Of all 610 cases, the main cause of injury was being run over (49.3%), followed by collisions (35.6%), and "other traffic accidents" (15.1%).
CONCLUSIONS
The analysis of the cases distributions and the type of care required corroborates with the need of a better organization of hospital care teams, more completeness of hospital reports and emphasis on some aspects in prevention campaigns. | 10.1590/s0034-89102000000400009 |
pubmed_6_16413 | BACKGROUND
Lactobacillus is a genus of Gram-positive non-spore-forming rods usually found in the microbiota of the oral cavity, gastrointestinal tract, and female genitourinary tract. Also, they are commonly used in the food industry as supplements and probiotics. Lactobacilli are normally considered non-pathogenic to the human body, however, under certain circumstances such as immunosuppression, they can cause severe infections, with only a few cases of bacteremia, infective endocarditis, pneumonia, meningitis, and intra-abdominal infections reported. Among these presentations, a pyogenic liver abscess is rather rare.
CASE PRESENTATION
We describe the case of a 59-year-old man with a history of diabetes mellitus and multiple abdominal surgeries with the latest being in 2014 presenting with bacteremia and multiple large pyogenic liver abscesses due to Lactobacillus gasseri, which did not appear to be related to the use of probiotics or immunosuppression.
CONCLUSIONS
Given the high prevalence of diabetes mellitus and the increased use of probiotics, it is expected that in the future we will see an increase in infections caused by Lactobacilli. Medical management with antibiotics and percutaneous drainage were successful strategies for the treatment of this unusual case of pyogenic liver abscesses and bacteremia caused by Lactobacillus gasseri. | 10.1186/s12879-021-06181-w |
pubmed_611_9664 | The purpose of this study was to evaluate, by histometric analysis, re-osseointegration following treatment of ligature-induced peri-implantitis in dogs. Five dogs were used in this study. Their mandibular premolars (P2, P3 and P4) were first removed. After 3 additional months of healing, two titanium implants were placed on each side of the mandible. After 3 months, the abutment connection was performed and experimental peri-implantitis was induced by placing cotton ligatures in a submarginal position. Ligatures and abutments were removed after one month and the peri-implant bone defects were randomly assigned to one of the treatments: debridement, debridement plus guided-bone regeneration, debridement plus mineralized-bone graft, and debridement plus guided-bone regeneration associated with mineralized-bone graft. Five months post-treatment, the degree of bone contact with the implant surface and the bone area within the threads were measured in 12 threads, the 6 most coronal at each side of each implant. One-way analysis of variance did not reveal statistically significant differences between the treatment modalities (p > 0.05). Within the limits of the present study, it can be concluded that there is a limited possibility of re-osseointegration around implant surfaces previously exposed by ligature-induced peri-implantitis. | 10.2334/josnusd.42.163 |
pubmed_240_10182 | In the title compound, C(25)H(32)O(3), the enone group adopts an s-cis conformation. The alk-oxy chain is in an all-trans conformation. The dihedral angle between the benzene rings is 7.86 (5)°. In the crystal, mol-ecules are connected by pairs of O-H⋯O hydrogen bonds, forming inversion dimers and giving R(2) (2)(10) rings. Within these dimers, weak C-H⋯O hydrogen bonds form two R(2) (2)(7) rings. In the crystal, the approximately planar mol-ecules [largest deviation for an atom being 0.4737 (12) Å for the terminal C atom of the alk-oxy chain] are arranged in sheets parallel to (20-1). Weak C-H⋯π inter-actions are also observed. | 10.1107/S160053681203872X |
pubmed_319_18219 | Cinnamaldehyde, an active compound of cinnamon, has been reported to exert various biological functions such as anti-inflammatory and anti-tumor activities. Previously, we showed that 2'-hydroxycinnamaldehyde (HCA) has an inhibitory effect on nitric oxide (NO) production through the inhibition of NF-κB signaling. In an effort to find a more effective anti-atherosclerotic agent, here we evaluated the anti-inflammatory effect of 2'-benzoyloxycinnamaldehyde (BCA) in RAW 264.7 murine macrophage cells. We showed that BCA more effectively inhibited NO production than HCA with less cytotoxicity. We also demonstrated that BCA inhibited the lipopolysaccharide (LPS)-induced expression of iNOS in a concentration-dependent manner. Signal transduction studies showed that BCA significantly inhibited the phosphorylation of SAPK/JNK and AP-1-dependent reporter gene activity. LPS-induced expression levels of JunB, c-Jun and c-Fos were also decreased by BCA treatment. Moreover, the LPS-induced DNA binding activity of AP-1 was markedly inhibited by BCA. The direct injection of BCA into mice inhibited the LPS-induced increase in plasma nitrite levels, confirming the anti-inflammatory effect of BCA in vivo. Overall, these observations suggest that BCA has the potential for use as an anti-atherosclerotic agent. | pubmed_319_18219 |
pubmed_367_5721 | UNLABELLED
Treatment of acute myocardial infarction has changed in recent years. Tremendous debate has developed over the efficacy of percutaneous coronary intervention compared with fibrinolysis. If primary percutaneous coronary intervention is available, it is the preferred treatment for acute ST segment elevation myocardial infarction.
AIM
Three months mortality of patients admitted to hospital with ST elevation myocardial infarction in city of Szombathely was analyzed.
METHODS
Mortality rates of two time periods were compared: year 2005 without primary percutaneous coronary intervention capability and year 2008 when local primary percutaneous coronary intervention was available.
RESULTS
In patient group with no longer than 12 hours ischaemic period 3 months mortality rate was lower in 2008 compared to 2005 (3.6% versus 15.6%). First of all, the relative high 3 months mortality rate in patient group treated with fibrinolytic therapy was responsible for this difference. Decreasing number of patients with longer than 12 hours ischaemic time in 2008 versus 2005 was also important.
CONCLUSION
Implementation of primary percutaneous coronary intervention for the management of ST segment elevation myocardial infarction patients in Szombathely was effective for patients' outcome. | 10.1556/OH.2009.28663 |
pubmed_992_20382 | Environmental and climatic change issues, population explosion, rapid urbanisation, depletion of fossil reserves, need for energy security, huge waste generation, etc. are some of the inherent issues associated with the fossil based linear economy which need greater attention. In this context, the world is gradually transforming from fossil-based economy to a sustainable circular bio-economy. The biogenic waste which is generated in enormous quanties in India can be considered as potential feedstock for structuring the bio-based economy. This communication depicts the need for developing waste derived bioeconomy in the Indian perspective. Waste is now being perceived as a resource with value and believed to supplement petroleum feedstock to a great extent if properly utilized. The necessity to introduce waste as the core element for the future economic models which also allows sustainable development is discussed. The review also establishes drivers for the bioeconomy and structures the waste derived bioeconomy in a sustainable format to address the futuristic needs, scope and opportunities envisaged in the business and economic realm. The enabling technologies/processes that can be applied for biogenic wastes valorisation are elaborated. Circularizing the economy in a waste biorefinery model for the production of biobased products including bioenergy is discussed. | 10.1016/j.nbt.2017.06.006 |
pubmed_522_16305 | The RAPTOR/KOG1 proteins are binding partners of the target of rapamycin (TOR) kinase that is present in all eucaryotes and plays a central role in the stimulation of cell growth and metabolism in response to nutrients. We show in this report that two genes are coding for RAPTOR/KOG1 homologs in the Arabidopsis and rice genomes. Disruption of the Arabidopsis AtRaptor1 gene leads to a very early arrest of embryo development whereas disruption of the AtRaptor2 gene, which is expressed at a lower level than AtRaptor1, has no visible effects on embryo and plant development. We also observed that mutations in the AtRaptor1 gene result in an earlier halt of embryo development than disruption of the AtTor gene. | 10.1016/j.bbrc.2004.11.117 |
pubmed_225_13117 | My initial experience with 20 patients undergoing Kock pouch continent urinary diversion is reviewed. The procedure has been slightly modified from that described by Kock and Skinner. All patients have been followed for at least four months (median, 33 months). There have been no early complications related to the pouch. The most significant problem, incontinence, has occurred in 2 patients (10%) at three and four months, respectively, after surgery. Only 1 of these patients required temporary use of an external appliance. Leakage was due, in both cases, to a patulous efferent nipple valve. Both were repaired by plication of the nipple, and no new efferent limbs were constructed. In 1 patient (5%) prolapse of the afferent limb associated with reflux and pyelonephritis developed one year post-surgery. Stones have developed in 3 patients (15%). All patients are currently continent and stone-free, and all are pleased with the result. | 10.1016/0090-4295(91)80201-h |
pubmed_1028_1146 | Seat belts reduce the severity of trauma in car accidents. There is a definite decrease in the percentage of head injuries, while abdominal lesions seem to increase. Experimental and clinical investigations show a predominance of abdominal wall injuries and liver ruptures. The seat belt syndrome requires close observation of the patient in the intensive care unit. An increasing number of late intestinal obstructions after a seat belt injury due to lesions of the intestinal wall are reported. | 10.1007/BF01579358 |
pubmed_525_7612 | A case of an anatomical variation of the arterial vessels in the popliteal fossa, leading to a vascular transection during a total knee revision is presented. The authors believe this complication should be considered in all cases of knee revision surgery. | 10.1007/s001670050157 |
pubmed_1053_6621 | A new binary vector system for Agrobacterium-mediated plant transformation was developed. A set of four mini-T vectors comprised of T-DNA border sequences from nopaline-type Ti-plasmid pTiC58 flanking a chimaeric hygromycin-resistance gene for selection of transformants and up to eight unique restriction sites for cloning foreign DNA was constructed on a broad-host replicon containing the oriV of plasmid pSa. In two of the constructs these multiple cloning sites are flanked by a strong promoter to activate transcription of inserted DNA in planta. High-efficiency transformation was prompted by a high-copy, stable virulence helper plasmid pUCD2614, which contains a cloned virulence region of pTiC58 and tandem copies of the par locus of plasmid pTAR. Southern blot hybridization and genetic analyses of the progeny of transformed plants showed that the hygromycin resistance gene was stably inherited. | 10.1007/BF00036911 |
pubmed_30_3612 | Action potentials of the second-order vestibular neurons of ten cats were recorded, both in rest and responding to sinusoidal and intense impulse acceleration stimuli. The data were compared with the far-field recorded vestibular-evoked response induced by the same impulse stimuli. It was found that the irregular (kinetic) neurons, which had a phase lead relative to head velocity, were capable of responding to these impulses with a latency as short as 3.5 msec after the start of head acceleration. It is assumed, therefore, that these neurons are the generators of the second wave of the vestibular-evoked response, having a similar latency. A high correlation was found between the latency of the first peak in the poststimulus time histogram in response to acceleration impulses and the phase of the response to sinusoidal rotations. The regular (tonic) vestibular neurons did not respond to acceleration impulses and probably did not contribute to the vestibular-evoked response. | 10.1288/00005537-198901000-00017 |
pubmed_796_6102 | The B6C3F1 mouse is a hybrid strain which exhibits a high (30%) spontaneous hepatoma incidence and sensitivity to chemical induction of liver tumors. The spontaneous hepatoma incidence of the paternal C3H/He strain is approximately 60%, while that of the maternal C57BL/6 strain is very low. The presence of activated oncogenes, primarily Ha-ras, and to a lesser extent, Ki-ras, has been reported in B6C3F1 mouse liver tumors. Because alterations in a gene's capacity for expression, as well as mutation, may be involved in oncogene activation, this investigation was directed toward an examination of a putative control point for transcription, i.e., the methylation state of a gene. Hypomethylation is believed to be necessary, but not sufficient, for transcription. It was therefore hypothesized that alterations in the methylation state of the Ha-ras and Ki-ras oncogenes may facilitate the aberrant expression of these genes in B6C3F1 mouse liver. Restriction enzyme analysis (MspI, HpaII, and HhaI) was used to assess the extent of DNA methylation. MspI digestion of B6C3F1 and C3H/He DNA revealed the absence of a 15-kb Ha-ras band present in MspI-digested C57BL/6 DNA, suggesting that the Ha-ras oncogene of B6C3F1 and C3H/He mouse liver lacks a methylated site. In other respects, the Ha-ras and Ki-ras oncogenes are methylated to a degree which suggests that these oncogenes have a low potential for expression in normal mouse liver. The methylation state of the Ha-ras and Ki-ras oncogenes was also assessed in benzidine-induced hepatomas and adjacent nontumor tissue from B6C3F1 mice. In four out of four cases, the Ha-ras oncogene was hypomethylated in tumor as compared to nontumor tissue and increased expression of the gene was detected in three out of four hepatomas; the Ki-ras oncogene was hypomethylated in two out of four cases. These results suggest that hypomethylation of oncogenes may provide an epigenetic mechanism for facilitating their aberrant expression. The lack of a methylated site observed in the Ha-ras oncogene in B6C3F1 and C3H/He mouse liver may indicate an increased potential for its expression which could, in part, account for the high propensity for hepatoma development in these two strains. | 10.1016/0041-008x(89)90288-3 |
pubmed_1065_15468 | A field study was conducted in which saliva samples were collected from a cohort of herbicide applicators during the pre-emergent spray season in Ohio in 1996. Atrazine concentrations were detected in human saliva samples using an enzyme-linked immunosorbent assay (ELISA) method. Trend due to atrazine exposure and subsequent elimination in the body were evidenced by the temporal pattern of decreasing atrazine concentrations in saliva over time. Median salivary concentrations of atrazine on non-spray days were significantly lower than on spray days for each sampling time (Mann-Whitney U-Wilcoxon rank sum test, P < 0.01). Within spray days, median salivary atrazine concentrations were significantly higher on days atrazine was sprayed than on days herbicides other than atrazine were sprayed for each sampling time (Mann-Whitney U-Wilcoxon rank sum test, P = 0.02 for 4 6 p.m. samples, P = 0.04 for bedtime samples, P = 0.03 for next-morning samples). Median salivary atrazine concentrations on days atrazine was sprayed were higher than the median concentration for the corresponding sampling time on non-spray days and on days when other herbicides were sprayed. Salivary concentration of atrazine is a plausible indicator of those days in which atrazine spraying was likely to have occurred. Salivary concentrations of atrazine not only reflect exposures resulting from spraying atrazine, but also exposures from other field activities where applicators may come in contact with atrazine. The results of this study confirmed data from animal experiments that atrazine is able to cross the cell membranes of salivary glands, and can be measured in human saliva with high sensitivity. The sampling method itself is convenient and easy to use in the field, with a high compliance rate, and analytical procedures are rapid and inexpensive. It is, therefore, concluded that saliva sampling of atrazine exposure among herbicide applicators is a feasible biomonitoring method. | 10.1007/s004200000174 |
pubmed_1042_7479 | Liposomes, as one of the most successful nanotherapeutics, have a major impact on many biomedical areas. In this study, we performed laser scanning confocal microscope (LSCM) and immunohistochemistry (IHC) assays to investigate the intra-tumor transport and antitumor mechanism of GE11 peptide-conjugated active targeting liposomes (GE11-TLs) in SMMC7721 xenograft model. According to classification of individual cell types in high resolution images, biodistribution of macrophages, tumor cells, cells with high epidermal growth factor receptor (EGFR) expression and interstitial matrix in tumor microenvironment, in addition, their impacts on intra-tumor penetration of GE11-TLs were estimated. Type I collagen fibers and macrophage flooded in the whole SMMC7721 tumor xenografts. Tumor angiogenesis was of great heterogeneity from the periphery to the center region. However, the receptor-binding site barriers were supposed to be the leading cause of poor penetration of GE11-TLs. We anticipate these images can give a deep reconsideration for rational design of target nanoparticles for overcoming biological barriers to drug delivery. | 10.1016/j.apsb.2019.06.011 |
pubmed_1037_22876 | In November 2015, the collapse of the Fundão dam (Minas Gerais, Brazil) carried over 40 × 106 m3 of iron ore tailings into the Doce river and caused massive environmental and socioeconomic impacts across the watershed. The downstream mudslide scavenged contaminants deposited in the riverbed, and several potentially toxic elements were further released through reduction and solubilization of Fe oxy-hydroxides under estuarine conditions. A turbidity plume was formed off the river mouth, but the detection of contaminants' dispersion in the ocean remains poorly assessed. This situation is specially concerning because Southwestern Atlantic's largest and richest reefs are located 70-250 km to the north of the Doce river mouth, and the legal dispute over the extent of monitoring, compensation and restoration measures are based either on indirect evidence from modeling or on direct evidence from remote sensing and contaminated organisms. Coral skeletons can incorporate trace elements and are considered good monitors of marine pollution, including inputs from open cut mining. Here, we studied a Montastraea cavernosa (Linnaeus 1767) coral colony collected 220 km northward to the river mouth, using X-rays for assessing growth bands and Laser Ablation Inductively Coupled Plasma Mass Spectrometry to recover trace elements incorporated in growth bands formed between 2014 and 2018. A threefold positive Fe anomaly was identified in early 2016, associated with negative anomalies in several elements. Variation in Ba and Y was coherent with the region's sedimentation dynamics, but also increased after 2016, akin to Pb, V and Zn. Coral growth rates decreased after the disaster. Besides validating M. cavernosa as a reliable archive of ocean chemistry, our results evidence wide-reaching sub-lethal coral contamination in the Abrolhos reefs, as well as different incorporation mechanisms into corals' skeletons. | 10.1016/j.scitotenv.2021.150880 |
pubmed_410_20913 | GOAL
Little is known about how physicians conceptualize leadership, what factors influence that conceptualization, and how their conceptualization may impact willingness to lead. We sought to explore how physicians conceptualize leadership.
METHODS
We conducted an exploratory study of data from a convenience sample of physicians across the United States using an anonymous, 54-item, online survey. We devised a novel leadership resonance score (LRS) to distinguish between leadership and management based on published definitions and prior pilot work. The activities fit on a spectrum from purely leadership actions to purely management actions, and we assigned a numeric value to each activity, allowing for quantification of a respondent's conceptualization of leadership as either more managing or more leading.
PRINCIPAL FINDINGS
There were 206 respondents (57% male; median age of 43 years [interquartile ranges, IQR: 32, 72]) who completed the survey. Respondents viewed leadership abilities to be highly important for physicians, with a median importance score of 80 (range 0-100, IQR: 50, 100). LRS indicated most physicians conflate leadership and management. Compared to other physicians, respondents assessed their own preparedness for leadership highly (median preparedness score: 70, IQR: 2, 100). Respondents' assessment of their preparedness for leadership was associated with age (Spearman's rho = 0.24, p < .001). LRS was not associated with preparedness for leadership (Spearman's rho = 0.12, p = .08). "Aversion to politics" was the most common barrier to interest in leadership (45%, 93/206), with "loss of personal time" being second (30%, 62/206).
APPLICATIONS TO PRACTICE
Our data demonstrate physicians misunderstand the differences between leadership and management. We surmise that if an accurate conceptualization of leadership by physicians is associated with increased willingness to lead, then educational activities designed to improve physicians' understanding of leadership could be beneficial in increasing physicians' willingness to take on leadership positions. An increased willingness by physicians to take on leadership roles would ultimately have a positive impact not only on individual patient care, but also on the healthcare system as a whole. | 10.1097/JHM-D-21-00036 |
pubmed_600_6569 | A simple and efficient MEKC method was developed to simultaneously determine human insulin, its five analogues, the main degradation products and the excipients usually present in injection formulations. A very fast method with a total analysis time of 3 min was then successfully validated for the analysis of human insulin and the quality control of commercial formulations was carried out. | pubmed_600_6569 |
pubmed_463_14244 | A simple, inexpensive and reproducible transformation method was developed for Gram-positive bacteria. It was based on agitation of bacterial protoplasts with glass beads in the presence of DNA and polyethylene glycol. By using this method, introduction of pGK12 into protoplasts of several strains of Gram-positive bacteria was achieved. | 10.1590/S1517-838220090004000025 |
pubmed_692_20082 | BACKGROUND
The objectives of this study were as follows: (1) to evaluate frontal sinus ostial patency following balloon dilation with the Ventera Sinus Dilation System, compared with frontal sinusotomy (Draf 2a); and (2) to compare mean blood loss and mean surgical time for frontal sinusotomy using balloon dilation compared with traditional surgical methods.
METHODS
A single blinded, randomized, controlled, prospective study was performed at St. Paul's Sinus Center, Vancouver, a tertiary referral rhinology center. Thirty patients undergoing functional endoscopic sinus surgery (FESS) for chronic rhinosinusitis (CRS) were randomized to a hybrid approach with exposure of the frontal recess using standard instrumentation and then balloon dilation of 1 frontal sinus drainage pathway and traditional frontal sinusotomy for the opposite side. Blood loss and surgical time for opening the frontal sinus drainage pathway was recorded for each side. Patients acted as their own controls. Ostial patency and size were assessed 5 weeks and 3 months postoperatively using endoscopy. Ostial patency was also recorded at 1 year following surgery.
RESULTS
All frontal sinus ostia in both groups (n = 30) were successfully opened and were patent with both techniques 3 months postoperatively. All frontal sinus ostia assessed at 1 year (73%) remained patent and none required revision frontal surgery. Balloon dilation showed a mean surgical time of 655 seconds compared to 898 seconds for traditional FESS (p = 0.03). Mean blood loss was less with balloon dilation (58 mL vs 91 mL; p = 0.008).
CONCLUSION
A hybrid balloon technique successfully dilates the frontal sinus drainage pathway with reduced blood loss. Also, short-term patency appears to be comparable to traditional frontal sinusotomy. | 10.1002/alr.21432 |
pubmed_278_22401 | The impact of body mass index (BMI) on surgical outcomes has previously been studied in relation to several oncological procedures. Regarding gastric cancer surgery, published results have been contradicting in terms of degree of technical difficulty, risk of postoperative complications and survival. In an attempt to clarify these issues, we performed a meta-analysis to evaluate the impact of obesity (defined as BMI ≥ 30 kg/m2) on outcomes after gastrectomy for gastric cancer. The meta-analysis was performed according to the PRISMA guidelines. Eligible studies were identified through search of PubMed, EMBASE, Web of Science and Cochrane Library databases. Quality assessment was performed using the Newcastle-Ottawa scale. The meta-analysis was conducted using random-effects modeling. A total of 11 studies with 13 538 patients were eligible for analysis. Obesity was associated with a significantly longer operation time (WMD = 19.38 min, 95% CI 12.72-26.04; p < 0.001), increased risk of overall complications (RR = 1.23, 95% CI 1.06-1.42; p = 0.005) and pulmonary complications (RR = 3.81, 95% CI 2.24-6.46; p < 0.001). These findings remained irrespective type of surgery (laparoscopic vs. open) and type of gastrectomy. No differences were found regarding blood loss, number of resected lymph nodes, anastomotic leakage, hospital stay, 30-day mortality and 5-year overall survival. The conclusion of the current meta-analysis is that high BMI in gastric cancer patients is associated with longer operative time and more frequent overall postoperative complications. However, it has no negative impact on survival, indicating that gastrectomy is a safe procedure for this group of patients. | 10.1016/j.asjsur.2021.04.033 |
pubmed_347_6236 | INTRODUCTION
End-stage renal disease and hemodialysis affect intraocular pressure (IOP). This study aimed to evaluate the effects of a one session of hemodialysis on IOP.
MATERIALS AND METHODS
In this study, the IOP of 130 eyes of 65 hemodialysis patients (38 men and 27 women) was measured before and every 1 hour after the initiation of hemodialysis therapy. Patients with any glaucomatous conditions were excluded. Demographic information including age, gender, underling systemic or ocular diseases, hemodialysis duration and frequency, KT/V, and levels of blood pressure, body weight, blood urea, serum sodium, serum potassium, blood glucose before and after hemodialysis were recorded.
RESULTS
The mean age of the patients was 60.3 +/- 16.7 years. The mean predialysis and postdialysis IOPs were 13.50 +/- 4.09 mm Hg and 12.73 +/- 4.07 mm Hg, respectively (P = .02). The mean IOP at the first and second hours (12.32 mm Hg and 11.83 mm Hg, respectively) of hemodialysis were significantly lower than the mean predialysis IOP (P < .001 for each). In nondiabetics, the mean IOP significantly decreased after hemodialysis. The mean predialysis and postdialysis blood glucose levels were significantly different between diabetics and nondiabetics, but were not significant in each group of diabetics and nondiabetics. There was a significant inverse relationship between IOP and blood glucose changes after hemodialysis (r = -0.180, P = .040).
CONCLUSIONS
Increased blood glucose levels significantly decreases IOP in hemodialysis patients without glaucomatous features. Changes in other metabolic parameters do not affect IOP during hemodialysis. | pubmed_347_6236 |
pubmed_98_24476 | We calculated the reliable change index (RCI) and clinically significant change (CSC) values for two widely used measures of posttraumatic stress disorder (PTSD): The Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) and the PTSD Checklist for DSM-5 (PCL-5) and examined how symptom changes at these thresholds related to improvements in psychosocial functioning. We used data from three independent samples of male military veterans, including two randomized controlled trials for PTSD (N = 198 for Sample 1 and N = 102 for Sample 2) and a cross-sectional study of primary care patients (N = 228). For Sample 1, within-person change in CAPS-5 and PCL-5 scores of ≥ 13 and 15, respectively, was indicative of reliable change. For Sample 2, within-person change in CAPS-5 and PCL-5 scores of ≥ 12 and 18, respectively, was indicative of reliable change. Scores of ≤ 8 and 28 on the CAPS-5 and PCL-5, respectively, indicated a participant is more likely to belong to the non-PTSD population than the PTSD population (i.e., clinically significant change) in both Samples 1 and 2. Participants who exhibited reliable or CSC reported significantly better psychosocial functioning at all posttreatment assessments than those who did not. Results provide thresholds for identifying clinically meaningful PTSD symptom change using these measures. Care should be taken to interpret these values appropriately and relative to numerous other definitions for meaningful symptom change. (PsycInfo Database Record (c) 2022 APA, all rights reserved). | 10.1037/pas0001098 |
pubmed_73_969 | The association of more than 140 genes with human photoreceptor degenerations, together with studies of animal models of these monogenic diseases, has provided great insight into their pathogenesis. Here we review the responses of the retina to photoreceptor mutations, including mechanisms of photoreceptor death. We discuss the roles of oxidative metabolism, mitochondrial reactive oxygen species, metabolic stress, protein misfolding, and defects in ciliary proteins, as well as the responses of Müller glia, microglia, and the retinal vasculature. Finally, we report on potential pharmacologic and biologic therapies, the critical role of histopathology as a prerequisite to treatment, and the exciting promise of gene therapy in animal models and in phase 1 trials in humans. | 10.1146/annurev-neuro-060909-153227 |
pubmed_429_1155 | Gram-negative organisms are not the most prevalent bacterial species found in renal abscesses. We postulate an ascending pathway for establishment of gram-negative abscesses. Voiding cystourethrography should be used in search of reflux. Surgical treatment remains the standard but early diagnosis may increase the effectiveness of parenteral antibiotics as definitive therapy. | 10.1016/s0022-5347(17)59179-x |
pubmed_869_3998 | BACKGROUND
Prior reports show that nebulized lidocaine might be an effective treatment for asthma.
OBJECTIVE
We sought to determine the anti-inflammatory and spasmolytic effects of lidocaine and its analogue, JMF2-1, which we have synthesized for reduced local anesthetic activity.
METHODS
Blockade of Na(+) currents was assayed in cultured GH(3) cells by using the patch-clamp technique, whereas anesthesia was assessed in a cutaneous pinching test in rats. Lidocaine and its analogue were nebulized into sensitized rats for evaluation of their effectiveness on airways spasm and inflammation induced by methacholine and allergen, respectively. Tissue histamine release and tracheal spasm triggered by allergen challenge in the absence and presence of these treatments were also examined in vitro.
RESULTS
The 50% inhibitory concentration values for blockade of Na(+) currents after treatment with JMF2-1 (25.4 mM) was remarkably higher than that of lidocaine (0.18 mM), which is consistent with the weak anesthetic capacity of this analogue. In contrast, JMF2-1 was more potent than lidocaine in inhibiting allergen-induced histamine release and tracheal spasm. In in vivo settings methacholine-induced increase in lung resistance (145%) significantly reduced to 72% and 47% after lidocaine and JMF2-1 treatment, respectively. Both treatments inhibited by about 81% allergen-evoked eosinophil accumulation into the lung tissue.
CONCLUSION
Replacement of the 2,6-dimethyl radicals by the 2-trifluormethyl group on the benzene ring of lidocaine significantly reduces anesthetic activity, preserving its ability to prevent key aspects of the allergic inflammatory response in the lung.
CLINICAL IMPLICATIONS
Nebulized JMF2-1 might be a means of achieving the antiasthmatic effects of lidocaine without the anesthetic effects. | 10.1016/j.jaci.2006.08.037 |
pubmed_417_10548 | Analogues of human growth hormone-releasing hormone-(1-30)-amide [GH-RH(1-30)-amide] were tested for their ability to stimulate GH release in vivo by injecting the peptides intravenously (iv), subcutaneously (sc), and intramuscularly (im). The analogues involved derivatization with Nle27 and Gaba substituents at the C-terminus with or without D-amino acid(s) in the peptide chain. The potency of the analogues was compared to that of GH-RH(1-29)-amid testing their ability to release GH at 5, 15 and 30 min after the administration. In iv test the potency of the analogues was 1.2-2 times higher than that of the GH-RH(1-29)-amide, and no significant differences were detected between the potencies of the analogues with or without D-amino acid. In the sc test the analogue with D-Ala2, Nle27, and Gaba30 substitutions expressed 8.0-51.7 times higher potency than the GH-RH(1-29)-amide, however, the analogue with similar modifications but with L-Ala2 showed the same low potency (1.2-2.1) as in the iv test. Results from the im experiments were similar to those of SC test. The most potent analogues were those which had D-Ala2, Nle27, and Gaba30 substitutions with Gly15 or Leu15. Circular dichroism (CD) spectra of the analogues showed that Leu in position 15 increased the stability of the predominant alpha-helix conformation, which improved the absorption of the molecule.(ABSTRACT TRUNCATED AT 250 WORDS) | 10.1007/BF03348930 |
pubmed_37_3132 | In this study, organic photovoltaic devices with single or double-layered active film were prepared from a stamping transfer technique. A P3HT/PCBM single-layered active layer and a ratio-controlled P3HT/PCBM double-layered active can be successfully fabricated with the help of ultraviolet curable polycarbonate films via a stamping transfer technique. The maximum conversion efficiency values 2.85 for a single active layer transferred device and 3.24% for an optimized double active layer transferred device. Even though transferred double layers should have a sharp interface boundary, an intermixed zone with a concentration gradient was generated by the interpenetration of a donor-rich layer and an acceptor-rich layer in a thermal annealing process. The generation of the intermixed zone is confirmed by Auger electron spectroscopy. The enhanced conversion efficiency levels are attributed to the increased efficiency of the carrier transporting process, which is due to the fact that the concentration gradient is combined with the efficient charge generation from the bulk heterojunction layers. | 10.1021/la100164k |
pubmed_82_343 | During a three-year study, 54 cows with toxic mastitis were examined and a number of clinical and laboratory measurements were taken. Twenty-five (46.3 per cent) of the cows died, and in comparison with those which survived, they had a significantly higher packed cell volume (PCV) (P < 0.01), longer eyelid skin tent time (P < 0.01) and lower rectal temperature (P < 0.01). In a model designed to predict the probability of survival, these variables correctly predicted survival in 84 per cent of cases and death in 73 per cent of cases. The cows with toxic mastitis had a significantly higher PCV than a normal cohort of cows sampled at the end of the study. | 10.1136/vr.143.5.127 |
pubmed_561_4848 | Disorder of androgen receptor function, generally due to mutations in androgen receptor gene, is one of the causes of male pseudohermaphroditism. The disorder results in a wide spectrum of abnormalities of male sexual development ranging from phenotypic female to male with infertility depending on residual androgen receptor function. Clinical features, endocrinological data and treatment of patients with the disorder were discussed. | pubmed_561_4848 |
pubmed_621_10434 | BACKGROUND
The sex chromosomes of Silene latifolia are heteromorphic as in mammals, with females being homogametic (XX) and males heterogametic (XY). While recombination occurs along the entire X chromosome in females, recombination between the X and Y chromosomes in males is restricted to the pseudoautosomal region (PAR). In the few mammals so far studied, PARs are often characterized by elevated recombination and mutation rates and high GC content compared with the rest of the genome. However, PARs have not been studied in plants until now. In this paper we report the construction of a BAC library for S. latifolia and the first analysis of a > 100 kb fragment of a S. latifolia PAR that we compare to the homologous autosomal region in the closely related gynodioecious species S. vulgaris.
RESULTS
Six new sex-linked genes were identified in the S. latifolia PAR, together with numerous transposable elements. The same genes were found on the S. vulgaris autosomal segment, with no enlargement of the predicted coding sequences in S. latifolia. Intergenic regions were on average 1.6 times longer in S. latifolia than in S. vulgaris, mainly as a consequence of the insertion of transposable elements. The GC content did not differ significantly between the PAR region in S. latifolia and the corresponding autosomal region in S. vulgaris.
CONCLUSIONS
Our results demonstrate the usefulness of the BAC library developed here for the analysis of plant sex chromosomes and indicate that the PAR in the evolutionarily young S. latifolia sex chromosomes has diverged from the corresponding autosomal region in the gynodioecious S. vulgaris mainly with respect to the insertion of transposable elements. Gene order between the PAR and autosomal region investigated is conserved, and the PAR does not have the high GC content observed in evolutionarily much older mammalian sex chromosomes. | 10.1186/1471-2164-13-226 |
pubmed_85_24573 | Traumatic brain injury (TBI) is not only a leading cause for morbidity and mortality in young adults (Bruns and Hauser, Epilepsia 44(Suppl 10):210, 2003), but also a leading cause of seizures. Understanding the seizure-inducing mechanisms of TBI is of the utmost importance, because these seizures are often resistant to traditional first- and second-line anti-seizure treatments. The early post-traumatic seizures, in turn, are a contributing factor to ongoing neuropathology, and it is critically important to control these seizures. Many of the available anti-seizure drugs target gamma-aminobutyric acid (GABAA) receptors. The inhibitory activity of GABAA receptor activation depends on low intracellular Cl-, which is achieved by the opposing regulation of Na+-K+-Cl- cotransporter 1 (NKCC1) and K+-Cl--cotransporter 2 (KCC2). Up-regulation of NKCC1 in neurons has been shown to be involved in neonatal seizures and in ammonia toxicity-induced seizures. Here, we report that TBI-induced up-regulation of NKCC1 and increased intracellular Cl- concentration. Genetic deletion of NKCC1 or pharmacological inhibition of NKCC1 with bumetanide suppresses TBI-induced seizures. TGFβ expression was also increased after TBI and competitive antagonism of TGFβ reduced NKKC1 expression, ameliorated reactive astrocytosis, and inhibited seizures. Thus, TGFβ might be an important pathway involved in NKCC1 up-regulation after TBI. Our findings identify neuronal up-regulation of NKCC1 and its mediation by TGFβ, as a potential and important mechanism in the early post-traumatic seizures, and demonstrate the therapeutic potential of blocking this pathway. | 10.1007/s00429-016-1292-z |
pubmed_541_16947 | Blockade of the effects of angiotensin II (Ang II) by using an angiotensin-converting enzyme (ACE) inhibitor has been proven to be of value in Type 1 diabetic nephropathy and in non-diabetic renal disease. Evidence in favour of Ang II blockade in Type 2 diabetic patients with renal damage is still lacking for ACE inhibitors (ACE-Is), while recent data indicate that angiotensin receptor blockers (ARBs) could be the drugs of choice in this situation. On the other hand, renal damage from the onset of disease is accompanied by a very significant increment in global cardiovascular risk. This fact, as well as that of simultaneous renal and cardiovascular protection, have to be considered for drug selection. In this sense, ACE-Is have been shown to be the drugs of choice when secondary cardiovascular prevention is required, while the evidence in primary prevention in hypertensive patients has been shown with losartan in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study. All these facts led to the conclusion that both ACE-Is and ARBs can be considered when both renal and cardiovascular protection are aimed for in Type 2 diabetic patients. | 10.3317/jraas.2003.016 |
pubmed_1043_7107 | Serum 25-hydroxy-vitamin D (25-OHD) concentrations were measured in 49 patients with hepatobiliary disease in infancy. Low mean values were found in groups of patients with biliary atresia, neonatal hepatitis, choledochal cyst, and chronic intrahepatic cholestatic syndrome. In the group of patients with surgically repaired biliary atresia, the mean value did not differ from normal. Parenteral vitamin D increased 25-OHD in serum in patients with biliary atresia, but did not do so in one patient with neonatal hepatitis. In contrast, oral vitamin D did not increase serum 25-OHD concentrations in patients with biliary atresia. It is concluded that the reduction of serum 25-OHD seen in biliary atresia was largely due to the malabsorption of vitamin D, while in neonatal hepatitis it was due to impairment of 25-hydroxylation of the vitamin. | 10.1136/adc.54.5.367 |
pubmed_337_17462 | Dyspnoea is a prominent symptom of chronic obstructive pulmonary disease (COPD). Recent multidimensional dyspnoea questionnaires like the Multidimensional Dyspnea Profile (MDP) individualise the sensory and affective dimensions of dyspnoea. We tested the MDP in COPD outpatients based on the hypothesis that the importance of the affective dimension of dyspnoea would vary according to clinical characteristics.A multicentre, prospective, observational, real-life study was conducted in 276 patients. MDP data were compared across various categories of patients (modified Medical Research Council (mMRC) dyspnoea score, COPD Assessment Test (CAT) score, Global Initiative for Chronic Obstructive Lung Disease (GOLD) airflow obstruction categories, GOLD "ABCD" categories, and Hospital Anxiety and Depression Scale (HADS)). Univariate and multivariate regressions were conducted to explore factors influencing the affective dimension of dyspnoea. Cluster analysis was conducted to create homogeneous patient profiles.The MDP identified a more marked affective dimension of dyspnoea with more severe mMRC, CAT, 12-item Short-Form Health Survey mental component, airflow obstruction and HADS. Multivariate analysis identified airflow obstruction, depressive symptoms and physical activity as determinants of the affective dimension of dyspnoea. Patients clustered into an "elderly, ex-smoker, severe disease, no rehabilitation" group exhibited the most marked affective dimension of dyspnoea.An affective/emotional dimension of dyspnoea can be identified in routine clinical practice. It can contribute to the phenotypic description of patients. Studies are needed to determine whether targeted therapeutic interventions can be designed and whether they are useful. | 10.1183/13993003.01998-2015 |
pubmed_626_9448 | OBJECTIVES
This study investigates vulnerabilities to deliberate self-harm (DSH) among adolescents, specifically focusing on peer victimization and alexithymia.
DESIGN
Correlational survey design.
METHODS
Three hundred and twenty-five secondary school students completed self-report questionnaires asking their history of DSH and bullying, and scales assessing alexithymia and depression.
RESULTS
Self-harming adolescents reported more victimization and alexithymic symptomology than participants who had never engaged in DSH. Alexithymia moderated, and partially mediated, the relationship between bullying and DSH. Bullying and DSH significantly co-varied when participants' alexithymia was moderate or high, but not when participants' alexithymia was low. The relationship between alexithymia and DSH was fully mediated by depression. The relationship between bullying and DSH was also moderated by depression. Depression moderated the relationship between alexithymia and DSH.
CONCLUSIONS
The findings suggest stressors in the social environment (e.g. bullying) are more likely to facilitate DSH when an adolescent has poor emotion regulation and communication skills and when an individual is experiencing mood difficulties. | 10.1348/014466509X441709 |
pubmed_149_23260 | The ability to efficiently perform actions immediately following instructions and without prior practice has previously been termed Rapid Instructed Task Learning (RITL). In addition, it was found that instructions are so powerful that they can produce automatic effects, reflected in activation of the instructions in an inappropriate task context. RITL is hypothesized to rely on limited working memory (WM) resources for holding not-yet implemented task rules. Similarly, automatic effects of instructions presumably reflect the operation of task rules kept in WM. Therefore, both were predicted to be influenced by WM load. However, while the involvement of WM in RITL is implicated from prior studies, evidence regarding WM involvement in instructions-based automaticity is mixed. In the current study, we manipulated WM load by increasing the number of novel task rules to be held in WM towards performance in the NEXT paradigm. In this task, participants performed a series of novel tasks presented in mini-blocks, each comprising a) instructions of novel task rules; b) a NEXT phase measuring the automatic activation of these instructed rules, in which participants advance the screen using a key-press; and c) a GO phase in which the new rules are first implemented and RITL is measured. In three experiments, we show a dissociation: While RITL (rule implementation) was impaired by increased WM load, the automatic effects of instructions were not robustly influenced by WM load. Theoretical implications are discussed. | 10.1371/journal.pone.0217681 |
pubmed_371_20528 | Spontaneous breaks in proteinaceous membranes on the surface of intraocular lenses are demonstrated with pathological and clinical methods. These breaks appear to be the result of traction and can be a horseshoe or radial-traction type. The breaks are repaired by the natural process of protein film deposition on the newly exposed area. | 10.1016/s0886-3350(13)81051-6 |
pubmed_1098_17402 | The future of clinical diagnosis and treatment of hematologic diseases will inevitably involve the integration of artificial intelligence (AI)-based systems into routine practice to support the hematologists' decision making. Several studies have shown that AI-based models can already be used to automatically differentiate cells, reliably detect malignant cell populations, support chromosome banding analysis, and interpret clinical variants, contributing to early disease detection and prognosis. However, even the best tool can become useless if it is misapplied or the results are misinterpreted. Therefore, in order to comprehensively judge and correctly apply newly developed AI-based systems, the hematologist must have a basic understanding of the general concepts of machine learning. In this review, we provide the hematologist with a comprehensive overview of various machine learning techniques, their current implementations and approaches in different diagnostic subfields (e.g., cytogenetics, molecular genetics), and the limitations and unresolved challenges of the systems. | 10.1016/j.blre.2022.101019 |
pubmed_979_10603 | After two years in which two-thirds of health maintenance organizations lost money, 1989 showed renewed vigor. Seventy percent of the healthcare organizations operating managed-care systems said their HMOs were profitable. | pubmed_979_10603 |
pubmed_374_9101 | BACKGROUND
Sexual identity is a significant risk factor for triggering symptoms of depression, as well as for suicide attempts in lesbian, gay and bisexual (LGB) population compared to the heterosexual population. To the best of our knowledge, data on the mental health of LGB persons in Serbia are lacking, and this is the first study to address this problem. The aim of the study was to examine the association between selected determinants and depression, and selected determinants and suicide attempts in LGB and heterosexual populations in the Republic of Serbia, as well as, their differences.
METHODS
We conducted a cross-sectional study in 2015 of 264 heterosexual and LGB respondents using the "snowball sampling" method. We used linear regression analyses to investigate the relationship between socio-demographic variables and different sexual identity categories with PHQ-9 scores. We assessed associations between suicide attempts, and socio-demographic characteristics, sexual identity, depression, and suicidal thoughts using logistic regression.
RESULTS
Depression symptoms were higher in female relative to male participants, in participants who were single, divorced or widowed in comparison to currently married, among people with a middle level of education compared to highly educated, and in respondents identified as bisexual or homosexual in comparison to heterosexual. Homosexual and bisexual participants reported suicidal attempts 27 [Odds Ratio (OR) = 27.31] and six times (OR = 6.40) more often than did heterosexual respondents, respectively. Suicide attempts were less frequently reported by single, divorced or widowed participants in comparison to married (OR = 0.25) and those with middle education (OR = 0.38) compared to highly educated.
CONCLUSIONS
The present study showed that LGB persons in Serbia have significantly more symptoms of depression and suicide attempts compared to heterosexuals. Public health interventions should focus on the early detection of depression and on overcoming prejudicial and discriminatory attitudes. Also, intervention should emphasize that homosexuality and bisexuality are normal, equal and morally acceptable expressions of human sexuality. | 10.1371/journal.pone.0234188 |
pubmed_408_9216 | The administration of haloperidol increased serum prolactin and decreased the pituitary concentration of prolactin 15 min after its administration. Concomitantly there was a stimulation in the synthesis of DNA and the activity of DNA polymerase alpha in the anterior pituitary gland that was greater in oestrogenized than in non-oestrogenized male rats. Both these effects were greatly reduced by clomiphene in the oestrogenized male rats, although it did not affect the release of prolactin produced by haloperidol. In non-oestrogenized animals clomiphene abolished the stimulatory effect of haloperidol on the synthesis of DNA. These results suggest that the reduction in the intracellular levels of prolactin are a primary event in the oestrogen mediated stimulation of cell proliferation by prolactin releasing agents. | 10.1055/s-2007-1018951 |
pubmed_704_25977 | Intercostal lung herniation is defined as a protrusion of the lung parenchyma through a defect in the intercostal muscles between adjacent ribs. The authors report a case of intercostal pulmonary hernia in a 45-year-old male patient, with smoking habit (30 packs-year), presented to the emergency department with dyspnea. He had the history of pulmonary emphysema complicated with a total right pneumothorax in 2015 treated by mini-thoracotomy with bullectomy and pleural abrasion. In 2019, he was admitted to hospital for left chest pain. The computed tomography (CT) scan of the chest revealed a bilateral emphysema with intercostal lung hernia through the fourth intercostal space the patient underwent, a left thoracotomy with repair of the intercostal muscle defect. He was discharged from hospital free of complications. | 10.11604/pamj.2020.36.39.20054 |
pubmed_232_22154 | Acetaminophen overdose causes toxicity in liver and extrahepatic tissues. Although it is well established that cytochrome P450 enzymes play a critical role in the metabolic activation of acetaminophen, it is not yet clear whether acetaminophen toxicity in extrahepatic tissues is a consequence of hepatic biotransformation. The aim of this study was to determine whether extrahepatic acetaminophen toxicity is altered in a mouse model that has liver-specific deletion of the NADPH-cytochrome P450 reductase (Cpr) gene. Liver-specific Cpr-null (Null) mice were resistant to acetaminophen hepatotoxicity, and they showed faster acetaminophen clearance than did wild-type mice at a toxic acetaminophen dose (400 mg/kg i.p.). However, when circulating acetaminophen levels were made equivalent in the two strains, the severity of extrahepatic acetaminophen toxicity was decreased in the Null relative to that in the wild-type mice in the lung, kidney, and lateral nasal glands, although not in the nasal olfactory and respiratory mucosa. In the lung and liver, the decreased acetaminophen toxicity was accompanied by substantial decreases in the formation of acetaminophen-protein adducts in the Null mice; adducts were not detected in other tissues examined. These results indicate that acetaminophen toxicity in the nasal mucosa is not dependent on hepatic microsomal P450-catalyzed metabolic activation and that acetaminophen toxicity in the lung, kidney, and lateral nasal glands is at least partly caused by liver-derived acetaminophen metabolites. | 10.1124/mol.104.007898 |
pubmed_409_7557 | The optimal cytotoxic treatment of patients with advanced breast cancer is so far not defined. Median survival after first metastatic manifestation is approximately 18 months. No direct evidence for a survival improvement after the introduction of cytotoxic therapy has been published. Major effects have been made to improve treatment efficacy through manipulations of doses, schedules and combinations of known cytotoxic drugs. Three months is probably too short a treatment period. Alternating non-cross resistant regimens offer no advantage over sequential therapy. A dose-response relationship clearly exists in breast cancer, but the higher response rates have not been transformed into a survival benefit. Treatment of advanced breast cancer is palliative, and if, furthermore, we have actually reached a plateau where no further improvement in survival is possible, we will have to evaluate every new treatment modality carefully according to quantity as well as quality of life. | 10.3109/02841869009090013 |
pubmed_197_8748 | In a national online survey, 505 participants reported their perceptions of energy consumption and savings for a variety of household, transportation, and recycling activities. When asked for the most effective strategy they could implement to conserve energy, most participants mentioned curtailment (e.g., turning off lights, driving less) rather than efficiency improvements (e.g., installing more efficient light bulbs and appliances), in contrast to experts' recommendations. For a sample of 15 activities, participants underestimated energy use and savings by a factor of 2.8 on average, with small overestimates for low-energy activities and large underestimates for high-energy activities. Additional estimation and ranking tasks also yielded relatively flat functions for perceived energy use and savings. Across several tasks, participants with higher numeracy scores and stronger proenvironmental attitudes had more accurate perceptions. The serious deficiencies highlighted by these results suggest that well-designed efforts to improve the public's understanding of energy use and savings could pay large dividends. | 10.1073/pnas.1001509107 |
pubmed_608_9005 | Considering how organisms adapt to stress is essential if we are to anticipate biological responses to global change in ecosystems. Communities in stressful environments can potentially be assembled by specialists (i.e. species that only occur in a limited range of environmental conditions) and/or generalist species with wider environmental tolerances. We review the existing literature on the salinity tolerance of aquatic insects previously identified as saline specialists because they were exclusively found in saline habitats, and explore if these saline realized niche specialists are also specialists in their fundamental niches or on the contrary are fundamental niche generalist species confined to the highest salinities they can tolerate. The results suggest that species inhabiting saline waters are generalists in their fundamental niches, with a predominant pattern of high survival in freshwater-low salinity conditions, where their fitness tends to be similar or even higher than in saline waters. Additionally, their performance in freshwater tends to be similar to related strictly freshwater species, so no apparent trade-off of generalization is shown. These results are discussed in the framework of the ecological and evolutionary processes driving community assembly across the osmotic stress gradient, and their potential implications for predicting impacts from saline dilution and freshwater salinization.This article is part of the theme issue 'Salt in freshwaters: causes, ecological consequences and future prospects'. | 10.1098/rstb.2018.0008 |
pubmed_171_13180 | Renal percent clearance ratios for various electrolytes were determined on nine clinically normal Holstein heifers. Endogenous creatinine serum and urine levels were used to calculate the ratios. The average percent clearance ratios and standard deviations of Na, K, Cl, P, and Ca were 1.97+/-0.63, 49.3+/-9.2, 3.16+/-1.l2, 15.6+/-14.3, and 1.38+/-1.41, respectively. The correlation between Na and Cl percent clearance ratios within a sample was 0.92. A very strong direct correlation of urine creatinine and urine specific gravity was demonstrated. | 10.1111/j.1939-165x.1985.tb00843.x |
pubmed_147_23938 | Future combinations of plasmonics with nanometer-sized electronic circuits require strategies to control the electrical excitation of plasmons at the length scale of individual molecules. A unique tool to study the electrical plasmon excitation with ultimate resolution is scanning tunneling microscopy (STM). Inelastic tunnel processes generate plasmons in the tunnel gap that partially radiate into the far field where they are detectable as photons. Here we employ STM to study individual tris-(phenylpyridine)-iridium complexes on a C60 monolayer, and investigate the influence of their electronic structure on the plasmon excitation between the Ag(111) substrate and an Ag-covered Au tip. We demonstrate that the highest occupied molecular orbital serves as a spatially and energetically confined nanogate for plasmon excitation. This opens the way for using molecular tunnel junctions as electrically controlled plasmon sources. | 10.1021/nl401177b |
pubmed_297_7241 | DNA topoisomerase II (Topo II) is crucial for resolving topological problems of DNA and plays important roles in various cellular processes, such as replication, transcription, and chromosome segregation. Although DNA topology problems may also occur during DNA repair, the possible involvement of Topo II in this process remains to be fully investigated. Here, we show the dynamic behavior of human Topo IIβ in response to DNA double-strand breaks (DSBs), which is the most harmful form of DNA damage. Live cell imaging coupled with site-directed DSB induction by laser microirradiation demonstrated rapid recruitment of EGFP-tagged Topo IIβ to the DSB site. Detergent extraction followed by immunofluorescence showed the tight association of endogenous Topo IIβ with DSB sites. Photobleaching analysis revealed that Topo IIβ is highly mobile in the nucleus. The Topo II catalytic inhibitors ICRF-187 and ICRF-193 reduced the Topo IIβ mobility and thereby prevented Topo IIβ recruitment to DSBs. Furthermore, Topo IIβ knockout cells exhibited increased sensitivity to bleomycin and decreased DSB repair mediated by homologous recombination (HR), implicating the role of Topo IIβ in HR-mediated DSB repair. Taken together, these results highlight a novel aspect of Topo IIβ functions in the cellular response to DSBs. | 10.1038/s41598-018-28690-6 |
pubmed_435_19293 | Nesfatin-1 is a hypothalamic anorexigenic peptide processed from nucleobindin 2 (NUCB2). Central and peripheral administration of NUCB2/nesfatin-1 enhances glucose metabolism and insulin release. NUCB2/nesfatin-1 is also localized in pancreatic islets, while its function remains unknown. To explore the role of pancreatic β-cell-produced NUCB2/nesfatin-1, we developed pancreatic β-cell-specific NUCB2 knockout (βNUCB2 KO) mice and NUCB2 gene knockdown (shNUCB2) MIN6 β-cell line. In βNUCB2 KO mice, casual blood glucose was elevated from 12 weeks of age. In a glucose tolerance test at 12 weeks, insulin secretion at 15 min was reduced and blood glucose at 2 h increased in βNUCB2 KO mice fasted 8 h. In islets isolated from βNUCB2 KO mice, high glucose-stimulated insulin secretion (GSIS) was impaired. In shNUCB2 MIN6 cells, GSIS was reduced and UCP-2 mRNA expression was elevated. These results show impaired GSIS possibly associated with UCP-2 overexpression in NUCB2-silenced β-cells, suggesting that β-cell-produced NUCB2/nesfatin-1 maintains GSIS and thereby glycemia. | 10.1007/s12576-019-00689-2 |
pubmed_581_23389 | Traditionally, G protein-coupled receptor antagonists are classified as competitive or noncompetitive and surmountable or insurmountable based on functional antagonism. P2Y1 receptor (P2Y1R) structures showed two antagonists binding to two spatially distinct sites: nucleotide MRS2500 (orthosteric, contacting the helical bundle) and urea BPTU (allosteric, on the external receptor surface). However, the nature of their P2Y1R antagonism has not been characterized. Here we characterized BPTU antagonism at various signaling pathways activated by structurally diverse agonists. BPTU rightward shifted the concentration-response curves of both 2-methylthioadenosine 5'-diphosphate trisodium salt and MRS2365 (5'-diphosphates) in some signaling events, such as extracellular signal-regulated kinase 1/2 and label free, in a parallel manner without affecting the maximum agonist effect (Emax) but antagonized insurmountably (suppressed agonist Emax) in signaling events such as guanosine 5'-3-O-(thio)triphosphate binding and β-arrestin2 recruitment. However, with dinucleotide Ap4A as an agonist, BPTU suppressed the Emax insurmountably in all signaling pathways. By comparison, MRS2500 behaved as surmountable antagonist rightward-shifting concentration-response curves of all three agonists in a parallel manner for all signaling pathways measured. Thus, we demonstrated a previously undocumented phenomenon that P2Y1R antagonism patterns could vary in different signaling pathways, which could be related to conformational selection, signaling amplification, and probe dependence. This phenomenon may apply generally to other receptors considering that antagonism by a specific ligand is often not compared at multiple signaling pathways. Thus, antagonism can be surmountable or insurmountable depending on the signaling pathways measured and the agonists used, which should be of broad relevance to drug discovery and disease treatment. | 10.1124/mol.117.109660 |
pubmed_762_12506 | A 58-year-old male presented with a dissecting aneurysm of the basilar artery manifesting as dysarthria, left hemiparesis, and numbness of the left side. Angiography revealed a double lumen at the midportion of the basilar artery which was consistent with a diagnosis of dissecting basilar artery aneurysm. The patient was treated conservatively, and remained neurologically stable for a 5-year period following initial presentation, but serial magnetic resonance imaging revealed growth of the aneurysm compressing the brain stem. His condition then worsened. Computed tomography revealed obstructive hydrocephalus. Ventriculoperitoneal shunting was performed and the patient's symptoms improved. However, he died of subarachnoid hemorrhage. Autopsy showed the patient had had a type 3 "dolichoectatic dissecting aneurysm." Surgical treatment should be seriously considered for treating the patients with dissecting basilar artery aneurysm causing brain stem ischemia, especially if the aneurysm is growing. High-flow bypass and proximal occlusion may be the choice in patients with poor collateral circulations. | 10.2176/nmc.42.560 |
pubmed_924_13975 | When guinea pigs are deafened with ototoxic drugs spiral ganglion cells (SGCs) degenerate progressively. Application of neurotrophins can prevent this process. Morphological changes of rescued SGCs have not been quantitatively determined yet. It might be that SGCs treated with neurotrophins are more vulnerable than SGCs in cochleae of normal-hearing guinea pigs. Therefore, the mitochondria and myelinisation of type-I SGCs were studied and the perikaryal area, cell circularity and electron density were determined. Guinea pigs were deafened with a subcutaneous injection of kanamycin followed by intravenous infusion of furosemide. Brain-derived neurotrophic factor (BDNF) delivery was started two weeks after the deafening procedure and continued for four weeks. Four cohorts of cochleae were studied: (1) cochleae of normal-hearing guinea pigs; (2) of guinea pigs two weeks after deafening; (3) six weeks after deafening; (4) cochleae treated with BDNF after deafening. The deafening procedure resulted in a progressive loss of SGCs. Six weeks after deafening the size of mitochondria, perikaryal area and cell circularity of the remaining untreated SGCs were decreased and the number of layers of the myelin sheath was reduced. In the basal part of the cochlea BDNF treatment rescued SGCs from degeneration. SGCs treated with BDNF were larger than SGCs in normal-hearing guinea pigs, whereas circularity had normal values and electron density was unchanged. The number of layers in the myelin sheath of BDNF-treated SGCs was reduced as compared to the number of layers in the myelin sheath of SGCs in normal-hearing guinea pigs. The morphological changes of SGCs might be related to the rapid loss of SGCs that has been reported to occur after cessation of BDNF treatment. | 10.1016/j.heares.2008.07.004 |
pubmed_501_2327 | Acute inhalation toxicity studies with diiodotetrafluoroethane in rats following an exposure of 4 h to concentrations of 6-197.5 ppm show that 16.5 ppm to 197.5 ppm impaired dose-related the animals' attitude and posture, motoricity, autonomic reactions and respiratory function. At concentrations of more than about 90 ppm death occurred as a result of cardiac and circulatory failure. On the basis of these results it could be demonstrated that the no-effect level is 6 ppm and the approximate mean lethal concentration (LC50) would be 75 ppm. | 10.1016/0378-4274(80)90107-1 |
pubmed_332_13701 | In the title compound, C(14)H(17)NO, the piperidinone and piperidine rings both adopt a chair conformation. The chiral crystals were obtained from a racemic reaction product via spontaneous resolution. | 10.1107/S1600536812020065 |
pubmed_411_6388 | The presence of tumor infiltrating lymphocytes (TILs) and tertiary lymphoid structures (TLSs) in tumor tissues are of great prognostic significance in several types of human cancer. The present study investigated the density of TILs and TLSs in gastric cancer (GC) tissues and their association with pathological parameters. Moreover, the clinical significance of follicular CD8+ cytotoxic T cells present within the germinal centers of the tumor-associated TLSs was investigated. Immunohistochemistry and H&E staining were used to examine the infiltration and distribution patterns of TILs, TLSs and germinal center (gc) CD8+ TILs in tumor tissues obtained from 63 patients with GC. The number of TILs, TLSs, combination of TILs and TLSs (TILs-TLSs) and gcCD8+ TILs were used to define tumoral immune parameters, and the prognostic value of these parameters was assessed. The analysis revealed that patients with GC with increased levels of TILs, TLSs, or gcCD8+ TILs exhibited improved overall survival. In addition, gcCD8+ TILs levels were significantly associated with patient age, histological grade and pTN stage. Increased levels of TILs-TLSs were positively associated with nerve invasion, tumor thrombus, nodal metastasis and histological grade. Multivariate Cox regression analysis revealed that TILs-TLSs and gcCD8+ TILs were independent prognostic factors. The data obtained in the present study demonstrated that high levels of tumoral immune parameters are important independent prognostic predictors for human GC. The results also suggested a possible role of gcCD8+ TILs in tumor immune surveillance. | 10.3892/ol.2020.11828 |
pubmed_556_24065 | Just as multiple sclerosis (MS) has long been primarily considered a white matter (WM) disease, Alzheimer's disease (AD) has for decades been regarded only as a grey matter disorder. However, convergent evidences have suggested that WM abnormalities are also important components of AD, at the same extent as axonal and neuronal loss is critically involved in MS pathophysiology since early clinical stages. These observations have motivated a more thorough investigation about the possible mechanisms that could link neuroinflammation and neurodegeneration, focusing on amyloid-β (Aβ). Neuroimaging studies have found that patients with AD have widespread WM abnormalities already at the earliest disease stages and prior to the presence of Aβ plaques. Moreover, a correlation between cerebrospinal fluid (CSF) Aβ levels and WM lesion load was found. On the other hand, recent studies suggest a predictive role for CSF Aβ levels in MS, possibly due in the first instance to the reduced capacity for remyelination, consequently to a higher risk of WM damage progression, and ultimately to neuronal loss. We undertook a review of the recent findings concerning the involvement of CSF Aβ levels in the MS disease course and of the latest evidence of AD related WM abnormalities, with the aim to discuss the potential causes that may connect WM damage and amyloid pathology. | 10.3233/JAD-200868 |
pubmed_664_15109 | PURPOSE
To verify the performance of children born preterm on auditory processing evaluation, and to correlate the data with behavioral hearing assessment carried out at 12 months of age, comparing the results to those of auditory processing evaluation of children born full-term.
METHODS
Participants were 30 children with ages between 4 and 7 years, who were divided into two groups: Group 1 (children born preterm), and Group 2 (children born full-term). The auditory processing results of Group 1 were correlated to data obtained from the behavioral auditory evaluation carried out at 12 months of age. The results were compared between groups.
RESULTS
Subjects in Group 1 presented at least one risk indicator for hearing loss at birth. In the behavioral auditory assessment carried out at 12 months of age, 38% of the children in Group 1 were at risk for central auditory processing deficits, and 93.75% presented auditory processing deficits on the evaluation. Significant differences were found between the groups for the temporal order test, the PSI test with ipsilateral competitive message, and the speech-in-noise test. The delay in sound localization ability was associated to temporal processing deficits.
CONCLUSION
Children born preterm have worse performance in auditory processing evaluation than children born full-term. Delay in sound localization at 12 months is associated to deficits on the physiological mechanism of temporal processing in the auditory processing evaluation carried out between 4 and 7 years. | pubmed_664_15109 |
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