Evidence for increased degeneration of mitochondria in old rats. A brief note.
An isotonic density gradient technique for separating mitochondria into two major components was applied to mitochondria isolated from young and old rats. Respiratory measuremtns indicate that the depression of state 3 respiration rates observed in the mitochondria from old rats when glutamate--malate is used as a substrate is due primarily to the faster sedimenting mitochondrial component.


Changes in nitric oxide production in the rat kidney due to CaOx nephrolithiasis.
The aim of the study was to test the hypothesis that the renal nitric oxide (NO) system is involved in the animal model of nephrolithiasis by evaluating the relationship between nitric oxide synthase (NOS) and oxidative stress. Deposition of renal calculi was induced by adding 0.75% ethylene glycol (EG) to the drinking water of male Wistar rats. After 42 days of treatment, urinary biochemistry and urinary levels of oxalate, NO metabolites (nitrate and nitrite), cGMP, and lipid peroxides, and markers for renal damage and oxidative stress in the kidney were examined. In the second part of the experiment, two diuretic stimuli (intrarenal infusion of l-arginine or saline loading) were applied to test the renal NO system response. Finally, levels of three isoforms of NOS in renal tissues were evaluated by immunostaining. In the EG-treated rats, increased urinary excretion of enzymes and lipid peroxides and increased nitrotyrosine levels and oxidative injury markers in the kidneys indicated that peroxynitrite formation occurred during oxidative stress, while the 24-hr urinary excretion of NO metabolites and cGMP remained unchanged. In contrast to control rats, urinary excretion and NO metabolites and cGMP excretion were unresponsive to intrarenal l-arginine infusion; in response to saline loading, an increase in these factors was seen, but the increase was only 50% of that seen in the identically treated control group. A significant decrease in eNOS expression and increase in iNOS expression were observed in the renal medulla of the EG-treated group, whereas expression of nNOS was not affected. Although basal renal NO production remained unchanged, excessive peroxynitrite formation in the kidney was noted in this model. A decreased response of the NOS system was noted when diuretic stimuli were applied. How the imbalance between eNOS and iNOS expression influences CaOx stone formation requires detailed evaluation.


A Sparse Bayesian Learning Algorithm for Longitudinal Image Data.
Longitudinal imaging studies, where serial (multiple) scans are collected on each individual, are becoming increasingly widespread. The field of machine learning has in general neglected the longitudinal design, since many algorithms are built on the assumption that each datapoint is an independent sample. Thus, the application of general purpose machine learning tools to longitudinal image data can be sub-optimal. Here, we present a novel machine learning algorithm designed to handle longitudinal image datasets. Our approach builds on a sparse Bayesian image-based prediction algorithm. Our empirical results demonstrate that the proposed method can offer a significant boost in prediction performance with longitudinal clinical data.


Simple and rapid method for the coding of punched cards.
A novel method for the coding of hand-sorted, edge-punched cards based in part on the phonetics of a word is outlined. The greatest utility of the scheme lies in its speed because of the elimination of a need of a controlled index. Experience gained in the operation of the new system is briefly described.


A prospective and multicenter safety-monitoring study of a short up-dosing schedule of immunotherapy with a mass-units-standardized extract of mites.
A prospective, multicenter pharmacovigilance study was carried out to evaluate the safety of a new 7-dose treatment schedule of subcutaneous immunotherapy as opposed to the conventional 13 doses normally recommended. The study was carried out in 14 centers and included 261 patients (children and adults) with respiratory allergic disease due to sensitization to mites (Dermatophagoides pteronyssinus and/or farinae). A total of 2290 doses were administered under the direct supervision of the participating specialists. One hundred and ten reactions in 63 patients (24.1%) were recorded, representing 4.8% of the total doses administered. Most of the reactions (98) were local. Only 12 were systemic (0.5% of the administered doses) and occurred in 10 patients (3.8% of the sample). Ten reactions reverted quickly with rescue medication. The maintenance dose had to be lowered in one patient and another patient was withdrawn from the study after suffering two asthmatic crises after two consecutive doses. In view of the results obtained, we can conclude that the new schedule shows an acceptable tolerance profile and does not present a greater risk of reactions than the conventional scheme of 13 doses using an identical extract. Moreover, the new schedule represents substantial savings in the number of doses and visits required to reach the maintenance dose.


Technological disaster--survival and bereavement.
Differences between natural and man-made disaster are described, deleterious psychological effects of technological components catastrophe appearing to be longer lasting. The psychological components of the experience of survival are outlined, and the concept of post-traumatic stress disorder located within this. Bereavement reactions, complicated by enhancement of the factors accompanying sudden, violent death, are also described, and risk factors noted. Finally, the development of community-based preventative mental health programmes which are acceptable to victims are detailed, emphasising restoration of the victims' sense of control over their own lives and the value of self-help. The role of counselling and specialist treatment is placed in this context.


Prognostic outcome after second primary lung cancer in patients with previously treated lung cancer by radiotherapy.
Second primary lung cancer (SPLC) occurs not rarely in recent years. The effect of radiotherapy on SPLC remains unclear. This study aims to explore the survival outcome of SPLC patients with clinical stage T1 lung cancer previously treated with radiotherapy. A total of 705 SPLC patients that previously underwent radiotherapy for first primary lung cancer (FPLC) were identified from the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2016. Univariate and multivariate Cox regression analyses were performed to find prognostic factors. The survival outcomes were plotted using Kaplan-Meier (KM) method and compared by log-rank test. Additionally, propensity score matching (PSM) analyses were used to compare overall survival (OS) and lung cancer-specific survival (CSS) between radiotherapy and other treatment groups for SPLC. According to Cox analyses, age >62 years [hazard ratio (HR): 1.48, 95% confidence interval (CI): 1.10-1.99; P=0.010], SPLC tumor size >1 cm (HR: 1.95, 95% CI: 1.51-2.53; P<0.001), and treatments for SPLC as chemotherapy (HR: 1.39, 95% CI: 1.13-1.71; P=0.002), no surgery (HR: 2.00, 95% CI: 1.34-2.98; P=0.001) and no radiotherapy (HR: 1.73, 95% CI: 1.39-2.15; P<0.001) independently indicated worse survival. After PSM, patients treated with radiotherapy for SPLC had significantly better OS and CSS than the none-treatment (OS: P=0.004; CSS: P<0.001), chemotherapy (P<0.001) or radiotherapy plus chemotherapy (OS: P=0.032; CSS: P=0.008) groups, but demonstrated a worse OS than the surgery group (P=0.034). Surgery may be more beneficial to survival than radiotherapy and chemotherapy and should be considered first if possible. When patients cannot tolerate surgery, radiotherapy can be an effective alternative.


Management of Moderate Blunt Thoracic Aortic Injuries in Patients with Intracranial Hemorrhage.
Blunt thoracic aortic injuries (BTAIs) are the second most common cause of death due to blunt-force trauma in the United States. Patients with minimal injuries do not typically require surgical repair, whereas patients with severe injuries are treated emergently. Moderate aortic injuries are repaired in a semielective fashion, but the optimal management of patients with moderate BTAI with associated intracranial hemorrhage (ICH) is unknown. We sought to analyze the management and outcomes of patients presenting with concomitant moderate BTAI and ICH. Consecutive patients who received a thoracic endovascular aortic repair (TEVAR) at our institution for treatment of moderate BTAI between January 2014 and December 2017 were retrospectively reviewed as part of an institutional review board-approved protocol. Patients were classified by our BTAI classification into "minimal", "moderate", or "severe". ICH was identified on computed tomography scan and its severity determined by the neurosurgical team. Outcome measures included surgical timing and surgical outcomes. Fifty-two patients had a moderate BTAI and underwent TEVAR, 20 (38 %) of whom presented with ICH. Median time from admission to surgery was 58.5 hr for patients with ICH and 26.5 hr for non-ICH patients. Intraoperative heparin was administered in all patients without ICH and in 19 of 20 (95%) patients with ICH after the ICH met criteria for stability. Protamine reversal was utilized in 80% of patients with ICH and 75% of non-ICH patients. No patient developed ischemic stroke or spinal cord ischemia. Worsening ICH was seen in only one patient, who also received heparin infusion for pulmonary embolus 24 hr before TEVAR. There were no aortic-related mortalities in either group. Thirty-day all-cause mortality was 5% for patients with ICH and 3% for non-ICH patients. Patients with moderate BTAI and stable ICH are not at increased risk of TEVAR-related complications. Administration of intraoperative heparin during TEVAR appears to be safe and does not worsen ICH.


Essential requirements of a CT colonography service.
There are many potential challenges to developing a high quality, efficient CT colonography service. Some are clear and predictable, for example creating CT capacity and securing financial resources, but some are less obvious, such as harnessing local support or changing referral practice amongst clinical colleagues. Notwithstanding, such barriers will need to be overcome to deliver a well-resourced, successful CT colonography programme. This article utilises the authors' experience of developing their own CT colonography service from scratch (now examining >1200 patients per annum) and relevant published articles on 'Standards' of practice and training to recommend how others might provide CT colonography in their own patient communities. We offer a practical guide and will emphasise the need for a multi-disciplinary approach with locally agreed protocols and service objectives.


Synthesis and biological evaluation of novel heteroring-annulated pyrrolino-tetrahydroberberine analogues as antioxidant agents.
Tetrahydroberberine (THB), otherwise known as canadine, is a natural alkaloid showing significant pharmacological properties and antioxidant protection against oxidative damage. Herein, we synthetized structurally complex THB analogues, namely pyrrolino-tetrahydroberberines (PTHBs) 4a-g, containing the pyrrolino[2,3-b]pyridine system, by means of the reactions of 1,2-diaza-1,3-dienes and 7,8-dihydroberberine. Aim of the study was to explore the in vitro antioxidant properties of PTHBs in comparison to THB thus to identify the most effective against free radical-induced oxidative injury, by using three different antioxidant tests: the ORAC method, the DNA nicking assay, and the DCFH-DA cellular assay. As a result, PTHB 4d emerged among the other THB analogues by exhibiting the best antioxidant properties. First, it was the only compound having an ORAC value completely comparable to that of THB, indicating the same ability to neutralize peroxyl radicals. Secondly, 4d showed an even better antioxidant capacity than THB in protecting DNA against ferrous ion-induced strand breaks. These observations were also confirmed in NCTC-2544 human keratinocytes exposed to hydrogen peroxide. Indeed, 4d protected cells against oxidation more efficiently than THB both in the short (1 and 3 h) and long (24 h) period of incubation, possibly suggesting increased cell membrane permeability and/or intracellular stability of 4d as compared to THB.


Synthesis, insecticidal, and antibacterial activities of novel neonicotinoid analogs with dihydropyridine.
Nilaparvata lugens, a major pest in rice-growing areas, is extremely difficult to manage. Neonicotinoids have increasingly been used in crop protection and animal health care against N. lugens. To discover new bioactive molecules and pesticides, we combined the active structure of cyanoacrylates, aromatic aldehydes, and substituted pyridyl (thiazolyl) methyl-2-substituted-methylidene-imidazolidine derivatives for the design and synthesis of a series of novel neonicotinoid analogs with dihydropyridine. A series of neonicotinoid analogs with dihydropyridine were synthesized. Their structures were characterized by IR, 1H NMR, 13C NMR, and elemental analysis and their insecticidal and antibacterial activities were assessed. Preliminary biological activity tests showed that all of the title compounds feature insecticidal activities against N. lugens at 500 mg/L. Moreover, some compounds showed promising antibacterial activities against Pseudomonas solanacearum (e.g., Tobacco bacterial wilt and Tomato bacterial wilt) at a dose of 200 mg/L. A synthetic route to obtain neonicotinoid analogs with dihydropyridine by the reaction of intermediates 2 (pyridyl (thiazolyl) methyl-2-substituted-methyl-ideneimidazolidine) and intermediates 1 (cyanoacrylates) and different aromatic aldehydes in acetonitrile under reflux conditions is presented. The effects of different solvents, bases, and reaction time on the reaction of 3a were investigated. The results of this study suggest that neonicotinoid analogs with dihydropyridine could cause N. lugens death and restrain P. solanacearum growth.


An algorithm and aesthetic outcomes for a coverage method for large- to medium-remnant microtia: I. Coverage in the one-stage erect position.
When reconstructing large- to medium-remnant microtia cases, one of the greatest dilemmas is how to deal with the variable shape and volume of the three-dimensional skin remnant for coverage of a newly sculptured three-dimensional framework. There are few guidelines for using the remnant skin adequately for achieving satisfactory aesthetic outcomes of the reconstructed ears. Nineteen large-remnant microtia patients who underwent reconstruction in the one-stage erect position between 2006 and 2010 were reviewed. According to the volume and shape of skin of the microtia remnant, different coverage methods were used. Aesthetic outcome in each case was evaluated by scores and, based on volume and shape of the remnant and the patient's final aesthetic scores, an algorithm for coverage methods is provided. Four coverage types were defined, and their application can be described in an algorithmic approach: three patients underwent reconstruction without additional skin coverage (option I); eight underwent reconstruction by the addition of a mastoid fascial flap into the conchal region (option II); one underwent reconstruction by the addition of an arterial skin flap (option III); and seven underwent reconstruction by the addition of a temporoparietal fascial flap into the superior auricle (option IV). Adequate reconstructive procedure, indications, and limitations for each case are presented. With the presented algorithmic approach, the remnant skin in each large-remnant microtia case was maximally and adequately used for reconstruction in the one-stage erect position by the least invasive surgical procedure. Better aesthetic outcomes are expected if this algorithmic approach is applied. Therapeutic, V.


High Hole Mobility and Efficient Ambipolar Charge Transport in Heterocoronene-Based Ordered Columnar Discotics.
Heterocoronene, a new redox-active core fragment, is utilized for the synthesis of room-temperature columnar discotic liquid crystals (DLCs). Three wedge-shaped side chains having different lengths of alkyl tails are introduced at the periphery of the heterocoronene core to prepare three kinds of discotic molecules, 1 (R = C10H21), 2 (R = C12H25), and 3 (R = C14H29). X-ray diffraction (XRD) analysis confirmed the packing variation in the columnar lattices regulated by alkyl chains of discrete length and steric bulk. When used in space charge limited current devices, compound 1 exhibits a high hole mobility value of 8.84 cm2/V s at ambient temperature, whereas compounds 2 and 3 show efficient ambipolar charge transport behavior with maximum hole (μh) and electron (μe) mobilities of 0.70 and 3.59 cm2/V s, respectively, for compound 3. The mobility values (μh = 8.84 cm2/V s for 1 and μe = 3.59 cm2/V s for 3) are remarkable and the highest ever disclosed for any DLC-based organic semiconductor, promising to deliver a good balance between mobility and processability in devices. The grazing incidence small- and wide-angle X-ray scattering experiments are employed to quantify the extent of alignment in the film state, which correlates with the observed trend of mobility values.


Choosing the appropriate measure of central tendency: mean, median, or mode?
Mean, median, and mode are among the most basic and consistently used measures of central tendency in statistical analysis and are crucial for simplifying data sets to a single value. However, there is a lack of understanding of when to use each metric and how various factors can impact these values. The aim of this article is to clarify some of the confusion related to each measure and explain how to select the appropriate metric for a given data set. The authors present this work as an educational resource, ensuring that these common statistical concepts are better understood throughout the Orthopedic research community.


Hepatic expression of MxA and OAS1 in an ex vivo liver slice assay independently predicts treatment outcomes in chronic hepatitis C.
Antiviral effect of interferon is mediated by the expression of interferon-stimulated genes (ISGs). However, because of the difficulty in obtaining paired liver biopsies before and after interferon treatment, the key ISGs expressed in human hepatocytes and responsible for interferon-based antiviral activities in chronic hepatitis C remain illusive. Prior to a standard course of peginterferon plus ribavirin therapy, 104 patients underwent a liver biopsy. A small piece of the liver biopsy sample from each patient was submitted for ex vivo tissue culture in the presence or absence of interferon. Hepatic expression of 8 ISGs was detected by RT-PCR. The ISG expression patterns and clinicopathological variables were correlated with subsequent treatment outcomes. Multivariate logistic regression analysis showed that hepatic MxA expression (P = 0.008) and leucocyte count (P = 0.040) independently predicted the end of therapeutic virological response, while hepatic OAS1 expression (P = 0.003), genotype 1 (P = 0.002), HCV-RNA level (P = 0.007), AST/ALT ratio (P = 0.004) and leucocyte count (P = 0.034) independently predicted the sustained virological response. Immunohistochemistry analysis showed that interferon-induced OAS1 expression localized to the hepatocytes. In conclusion, hepatic MxA and OAS1 expression predicted, respectively, the end of therapeutic and sustained virological responses in interferon-based treatment of chronic hepatitis C.


The necessity of a more aggressive initial surgical treatment in patients with mesothelioma of the testicular tunica vaginalis.
Mesothelioma of the tunica vaginalis of the testis (MTVM) is a rare tumor encountering for less than 1% of mesothelioma. Patients suffering from these tumors have poor survival due to local and distant metastasis despite treatment. Actually, no specific treatment recommendations exist for this tumor, yet radical orchidectomy is the gold standard in limited disease. We herein report the case of a 71 patient with MTVM who underwent radical orchidectomy without inguinal lymph node dissection and recurred 2 years later with metastasis in pelvic and mediastinal lymph nodes. Despite systemic chemotherapy combining pemetrexed, bevacizumab and Cisplatinum, the disease relapsed eight months later with multiple metastatic lung nodules leading to a treatment shift. We believe that systematic inguinal-iliac lymph node resection should be included in the initial treatment of this tumor.


Victimization among adolescents of female sex workers: findings from the children of at-risk parents (CARP) study in Uganda.
Female sex workers (FSWs) live and work in high-risk environments, experience high levels of adversity, and have multigenerational trauma that can negatively affect their children. Yet not much is known about the prevalence of victimization (i.e., exposure to maltreatment and trauma) among children of FSWs. This study compared the prevalence of lifetime victimization among adolescents of FSWs and adolescents of non-FSWs in Gulu City, Northern Uganda. A comparative cross-sectional study was conducted among adolescents (10-17 years) enrolled in the Children of At-Risk Parents (CARP) study. This study included 147 adolescents of FSWs and 147 adolescents of non-FSWs selected for comparison in Gulu City, Northern Uganda. The adolescents of FSWs were identified through their mothers using respondent-driven sampling. Data on the residence of FSWs guided a proportionate stratified sampling of adolescents of non-FSWs. Using the Juvenile Victimization Questionnaire, we screened for 34 different types of victimization during participants' lifetimes. Percentage point differences within groups of adolescents and comparison between adolescents of FSWs and non-FSWs were calculated using STATA version 14.1. Statistical significance was set to p < 0.05. 99.3% of the participants experienced at least one form of lifetime victimization. The median number of lifetime victimizations was 12.4. Overall, lifetime victimization was higher among adolescents of FSWs than non-FSWs (13.4 vs. 11.5), male vs. female adolescents (13.4 vs. 11.9), and older [14-17 years] vs. younger (10-13 years) adolescents (14.0 vs. 11.7). Further, more adolescents of FSWs experienced lifetime victimization in the following domains and subdomains, all of which were statistically significant: kidnap (15.8% vs. 4.8%), emotional abuse (65.8% vs. 50.0%), emotional neglect (37.4% vs. 21.1%), physical intimidation (10.2% vs. 4.1%), relational aggression (36.4% vs. 18.4%), verbal aggression (68.7% vs. 46.9%), sexual victimization (31.3% vs. 17.7%), verbal sexual harassment (20.4% vs. 5.4%), exposure to murder scene (42.9% vs. 26.5%), witness to domestic violence (39.5% vs. 26.5%), and witness to the murder of relatives (31.3% vs. 21.1%). Conversely, more adolescents of non-FSWs experienced caregiver victimization than the adolescents of FSWs (98.0 vs. 92.5; p < 0.05). Childhood victimization is highly prevalent in Northern Uganda and disproportionately affects the adolescents of FSWs. Therefore, government and development partners should urgently develop policies and interventions targeting prevention, early detection, and timely management of victimization in this vulnerable population.


Purification and properties of a low molecular weight DNA polymerase from Neurospora crassa.
A third DNA polymerase 'C' with low molecular weight was isolated and purified 3700-fold from ground hyphae of Neurospora crassa WT 74 A, which shows similarities to beta- and gamma-polymerases from higher eukaryotes: preference for poly(rA)(dT) as a template/primer, inhibition by p-chloromercuribenzoate, resistance against N-ethylmaleimide up to 10 mmol/l, and molecular weight of about 40000. This polymerase elutes as a distinct peak from DEAE-cellulose at 0.60 mol/l KCl and has an optimum for K+ at 2-20 mmol/l, for Mn2+ at 0.8 mmol/l, for Mg2+ at 4.0 mmol/l, the pH optimum is 8.0. Its Km is 1.5 mumol/l using dTTP as substrate. The enzyme activity described here is free of endonuclease but contains detectable amounts of exonuclease.


Macrophage Polarization Induced by Probiotic Bacteria: a Concise Review.
Macrophages display remarkable plasticity and can possess distinct functions in response to different environmental stimuli. Classically activated macrophages (M1 macrophages) are pro-inflammatory and have a critical role in host defense against infection, while alternatively activated macrophages (M2 macrophages) suppress inflammatory responses and associated with wound repair. Probiotic bacteria are reported to have a beneficial effect on the host immune status through their ability to modulate the macrophage polarization. Some probiotic strains are reported to activate macrophages to M1 phenotype to kill intracellular pathogens, while some other probiotics can induce M2 macrophages to exert the anti-inflammatory effect. Thus, this review will focus on the immunomodulatory role of probiotics in macrophage polarization and summarize the mode of action of probiotics in regulating macrophage plasticity. The detailed understanding of the immunomodulatory signaling effects of probiotic bacteria will broaden our understanding of how probiotics may regulate the immune system and find their therapeutic potentials for inflammatory diseases.


The reduction of implant-related errors and waste in total knee arthroplasty using a novel, computer based, e.Label and compatibility system.
Implant related errors and wasted arthroplasty implants represent a significant problem in the healthcare system. Studies estimate that an implant is wasted in two to five percent of total joint replacement procedures. After the introduction of a standardized time-out procedure, our institution still had a wasted implant in one out of every 20 arthroplasty surgeries. We then implemented a computer based, e.Label and compatibility system which standardized the implant labeling, confirmed correct size and side, and ensured compatibility within implant systems. Use of this system decreased wasted implants from 5.7% to 0.8% of total knee arthroplasty cases. This translated to an annualized cost savings of over $75,000 over our study period which could extrapolate to over $82 million per year in savings to the US healthcare system.


Large pelvic masses of obscure origin: urologist's perspective.
Large pelvic masses pose unique diagnostic and therapeutic challenges due to varied aetiology, paucity of characteristic imaging features, lack of therapeutic algorithms and surgical difficulties in resection inside the narrow confines of the pelvis with close proximity of vital structures. Records of 22 patients with large pelvic masses in the last six years were analysed. Their demographic and clinical features were noted, along with imaging features, preoperative biopsy, surgical procedure, intraoperative difficulties, complications, adjuvant therapy and outcome. There were 14 men and 8 women with a median age of 45 years. Presenting symptoms were abdominal mass, pain, lower urinary tract symptoms, urinary retention and constipation. Imaging was mostly unable to determine the organ of origin of the tumour. Histopathology revealed pelvic fibromatosis (2), chondrosarcoma (1), liposarcoma (1), haemangioendothelioma (1), lymphangioma (2), fibroleiomyoma (1), leiomyosarcoma (3), schwannoma (4), malignant nerve sheath tumour (1), rectal gastrointestinal stromal tumour (1), retrovesical hydatid cysts (3), sacral chordoma (1) and Ewing's sarcoma (1). In 5 patients complete excision was not possible because of extension into vital structures. Fifteen patients were alive at 1-5 years of follow-up. Urologists, being the 'gatekeepers of the pelvis', are usually involved in the management of large pelvic masses. Good outcome can be achieved with careful surgical planning.


Analysis of immune responses and serological cross reactivities among Vibrio cholerae O1, Shigella flexneri 2a and Haemophilus influenzae b.
Antigenic determinants expressed on the bacterial cell surface are of importance in the serological characterization and microbiological diagnosis. The bacterial strains carrying these identical or similar antigenic epitopes might react with antibodies produced against other strains. In this study, strong immunogenicity and antigenic cross reactivity were demonstrated among V. cholerae O1, S. flexnerii 2a and H. influenzae b surface components. The enzyme linked immunosorbent assay (ELISA) results were supported by Western blot analysis, where at least 20 antigenic bands, were obtained in each of the reactions, when the surface components were reacted with the homologous antisera. The indirect ELISA results also demonstrated high degree of antigenic relatedness between the surface components of these species, where each surface component was reacted with the heterologous antisera. Western blot analysis also revealed cross reactions between the surface components suggesting common distribution of antigens/epitopes in these bacterial species. This study, thus, gave a clear idea of the level of antigenic sharing and variations among the pathogenic V. cholerae O1, S. flexneri 2a and H. influenzae b strains, which in future, may help in selecting a proper candidate for vaccines and immunodiagnostics development.


Expression of staphylococcal clumping factor A impedes macrophage phagocytosis.
Clumping factor A (ClfA), a fibrinogen-binding protein linked to the Staphylococcus aureus cell wall, is an important virulence factor in infection models, e.g., of septic arthritis. However, the mechanism(s) by which ClfA contributes to the virulence of the bacterium is unknown. In the present study, the impact of ClfA expression on the phagocytosis of S. aureus by macrophages was investigated using clfA-positive and clfA-negative isogenic strains. Furthermore, the possible contribution of ClfA to the proinflammatory and immunostimulatory activity of S. aureus was studied. Our results indicate that ClfA expression significantly protects S. aureus against macrophage phagocytosis. This protection does not require the presence of intact fibrinogen, a ligand for ClfA. ClfA expression by S. aureus enhanced the proliferative response of spleen cells. On the other hand, a clfA mutant strain caused more release of proinflammatory mediators by macrophages than its clfA-positive parental strain. Both the protection against phagocytosis and the enhanced immunostimulatory activity provided by ClfA expression are likely to contribute to the in vivo virulence of S. aureus.


Packed-column supercritical fluid chromatography of artemisinin (qinghaosu) with electron-capture detection.
In this preliminary report, a supercritical fluid chromatographic method is described for the determination of artemisinin in whole blood. The chromatography is carried out on a 20 cm x 1 mm I.D. Deltabond cyano supercritical fluid chromatographic column with detection of the artemisinin via an electron-capture detector. The sample work-up uses a liquid-liquid extraction with hexane, giving a recovery of 82%. The current limit of detection using 1 ml of blood is 20 ng/ml. We speculate that the endoperoxide moiety accounts for the response to the electron-capture detector and thus provides a new approach by which this class of compounds may be analyzed.


Activation of peroxydisulfate by a novel Cu0-Cu2O@CNTs composite for 2, 4-dichlorophenol degradation.
In this study, a novel Cu0-Cu2O@CNTs composite was synthesized, characterized and applied to activate peroxydisulfate (PDS) for the degradation of 2, 4-dichlorophenol (2,4-DCP) in contaminated lake water. The results indicated that Cu0-Cu2O@CNTs can effectively activate PDS to produce O2•- radical, which has high selectivity to degrade organic pollutants in actual contaminated water. The efficiency of 2,4-DCP degradation and mineralization was 99.27% and 66.90%, respectively under the optimal condition. In the presence of Cl-, HCO3- and natural organic matters (NOMs) or in real wastewater containing 2,4-DCP, Cu0-Cu2O@CNTs/PDS system had a good selectivity for 2,4-DCP degradation. O2•- was the dominant reactive species in Cu0-Cu2O@CNTs/PDS system for 2,4-DCP degradation. The possible degradation pathway of 2,4-DCP was proposed. It was concluded that Cu0-Cu2O@CNTs composite could overcome the shortcomings of PDS activation by Cu0 and Cu2O alone, such as low activating capability of Cu0 and instability of Cu2O, which was high efficient for activating PDS. Cu0-Cu2O@CNTs composite can be used as an efficient catalyst to activate PDS for the degradation of toxic organic pollutants in water and wastewater.


Impact of availability of guidelines and active surveillance in reducing the incidence of ventilator-associated pneumonia in Europe and worldwide.
To analyse whether the availability of written standards for management of mechanically ventilated patients and/or the existence of a surveillance system for cases of ventilation-associated pneumonia (VAP) are positively associated with compliance with 6 well-established VAP prevention measures. Ecological study based on responses to an online-questionnaire completed by 1730 critical care physicians. Replies were received from 77 different countries, of which the majority, i.e. 1351, came from 36 European countries. On a cross-country level, compliance with VAP prevention measures is higher in countries with a large number of prevention standards and/or VAP surveillance systems in place at ICU level., Likewise, implementation of standards and VAP surveillance systems has a significant impact on self-reported total compliance with VAP prevention measures (both p < 0.001). Moreover, predictions of overall prevention measure compliance show the effect size of the availability of written standards and existence of surveillance system. For instance, a female physician with 10 years of experience in critical care working in a 15-bed ICU in France has a predicted baseline level of VAP prevention measure compliance of 63 per cent. This baseline level increases by 9.5 percentage points (p < 0.001) if a written clinical VAP prevention standard is available in the ICU, and by another 4 percentage points (p < 0.001) if complemented by a VAP surveillance system. The existence of written standards for management of mechanically ventilated patients in an ICU and the availability of VAP surveillance systems have shown to be positively associated with compliance with VAP prevention measures and should be fostered on a policy level.


Chronotype and work shift in nursing workers of university hospitals.
To identify the predominant chronotype in nursing workers who work in surgical clinics of university hospitals and to verify the association with work shift. Cross-sectional study, performed in surgical clinics of university hospitals in the Southern region of Brazil. The sample of 270 nursing workers answered questions of socio-occupational characterization, of health and the Morningness-Eveningness Questionnaire of Horne and Östberg. We performed a descriptive and bivariate analysis with the help of the SPSS software and confidence interval of 95%. The indifferent chronotype predominated (45.2%). There were significant differences between occupational categories and variables "age" (p<0.001), "use of medication" (p=0.035) and "choice of work shift" (p=0.001). There was an association between the chronotype and the variables "work leave due to illness" (p=0.021), "children" (p=0.025), "use of medication" (p=0.018) and "work shift" (p=0.001). The chronotype remained indifferent, and the results confirmed association between chronotype and work shift. Identificar o cronotipo predominante em trabalhadores de enfermagem que atuam em clínicas cirúrgicas de hospitais universitários e verificar associação com o turno de trabalho. Estudo transversal, realizado em clínicas cirúrgicas de hospitais universitários da região Sul do Brasil. A amostra de 270 trabalhadores de enfermagem respondeu questões de caracterização sociolaboral, de saúde e o Questionário de Matutinidade-Vespertinidade de Horne e Östberg. Realizou-se análise descritiva e bivariada com auxílio do software SPSS e intervalo de confiança de 95%. Predominou o cronotipo indiferente (45,2%). Houve diferença significativa entre as categorias profissionais e as variáveis "idade" (p<0,001), "uso de medicação" (p=0,035) e "opção pelo turno de trabalho" (p=0,001). Foi identificada associação entre o cronotipo e as variáveis "afastado do trabalho por motivo de doença" (p=0,021), "filho(s)" (p=0,025), "uso de medicação" (p=0,018) e "turno de trabalho" (p=0,001). Predominou o cronotipo indiferente, e os resultados confirmaram a associação entre cronotipo e turno de trabalho.


Comparison Between Nailing and Plating in the Treatment of Distal Tibial Fractures: A Meta-Analysis.
To evaluate evidence on the superiority of plate fixation over intramedullary nail fixation in the treatment of distal tibial fractures regarding functional outcomes and complication rates. Cochrane Controlled Trials Register, Medline, Embase, CINAHL, Scopus, and Web of Science databases were searched in December 2019. The risk of systematic bias was assessed according to the Cochrane Collaboration's domain-based evaluation framework. The search resulted in 514 records, the final sample included 10 randomized controlled trials (782 patients). There were statistically significant differences in operating time (-11.2, 95% confidence interval: -16.3 to -6.1 min), time to partial weight bearing (-0.96, 95% confidence interval: -1.8 to -0.1 weeks), time to full weight bearing (-2.2, 95% confidence interval: -4.32 to -0.01 weeks), the rates of deep infections (risk ratio = 0.37, 95% confidence interval: 0.19 to 0.69), and the rates of soft-tissue complications (risk ratio = 0.52, 95% confidence interval: 0.33 to 0.82) favoring intramedullary nail. Intraoperative blood loss (127.2, 95% confidence interval: 34.7 to 219.7 mL) and postoperative knee pain and stiffness (relative risk = 5.6, 95% confidence interval: 1.4-22.6) showed significant differences favoring plate fixation. When combining all complication rates, the difference was risk ratio = 0.77 (95% confidence interval: 0.63 to 0.95) favoring intramedullary nail. No significant differences in radiation time, length of incision, length of hospital stay, time to return to work, time to union, the rates of healing complications or secondary procedures, ankle pain or stiffness, or functional scores were found. This meta-analysis suggests that intramedullary nail might be slightly superior in reducing postoperative complications and result in slightly faster healing when compared to plate fixation.


Internalization of a monoclonal antibody against human breast cancer by immunoelectron microscopy.
Using an avidin-gold conjugate, the binding and internalization of the biotinylated anti-breast cancer monoclonal antibody MBr1 in MCF-7 cells were examined. After labelling MCF-7 cells at 0 degrees C, MBr1 was found to specifically bind to the entire cell surface. MBr1 distribution was diffused in cells fixed before labelling, but appeared in patches of different sizes in cells immediately fixed after labelling. On warming prelabelled cells at 37 degrees C for 2 min, MBr1 was internalized through non-coated small invaginations and vesicles an also through smooth invaginations with coated regions at the bottom. After warming for 15 and 30 min to 37 degrees C, the MBr1 internalization sites were observed as large membrane invaginations, large vesicular structures and lysosomes. The early steps of MBr1 internalization which consists of non-coated micro-invaginations seem to be correlated to the glycolipidic nature of the MBr1 recognized molecule. The MBr1 ability to enter MCF-7 cells suggests that this anti-tumour monoclonal antibody may be used as a toxin ability to enter MCF-7 cells suggests that this anti-tumour monoclonal antibody may be used as a toxin carrier agent.


Pain in gynecologic practice.
This paper has given a general discussion of the spectrum of pain complaints presented to the gynecologist. Specific information about pain sensation and localization has been reviewed together with the gynecologic causes of acute abdominal pain. Chronic pain has been classified as episodic or continuous, and the causes, mechanisms, diagnosis and treatment of episodic and chronic pelvic pain have been presented. The concluding remarks have outlined some diagnostic considerations for the patient with chronic pain. (The interested reader will find more extensive information on these subjects in the articles listed in the bibliography.).


Ce/Eu redox couple functionalized HKUST-1 MOF insight to sono-photodegradation of malathion.
The Ce/Eu redox pair-functionalized HKUST-1 MOF, as an innovative environmentally friendly and recyclable sono-photocatalyst, was hydrothermally mixed and fully characterized by XRD, PL, EIS, FE-SEM, EDS, Mott-Schottky, chronoamperometry, and DRS techniques. The obtained chemical and optical characteristics of the n-type Ce/Eu-HKUST-1 MOF showed that the transfer of additional 4f orbital electrons in the Ce/Eu redox pair improves the sono-photocatalytic activity. The performance of Ce/Eu-HKUST-1 MOF for the sono-photodegradation of Malathion (MA) was evaluated in the aqueous media in the simultaneous presence of blue light and ultrasonic irradiation. The optimization of the process was cross-examined using the response surface methodology as a function of the MA concentration (15-35 mg·L-1), Ce/Eu-HKUST-1 mass (10-30 mg), pH (4-12), and ultrasonic wave irradiation duration (10-30 min). The maximum sono-photocatalytic degradation capacity was found to be 99.99% under the optimum conditions set as 25 mg·L-1, 20 mg, 8, and 25 min for the concentration of Malathion, photocatalyst mass, pH, and irradiation duration, respectively. These findings were attributed to the suppression of electron-hole pair recombination, increased life-time of charge carriers, enhanced visible light absorption, and prominent proportion of hydroxyl and peroxide radicals formed.


Medial orbital wall decompression: Demographics influencing surgical follow-up and complications: Impacts on follow-up and complications.
Identify the impact of demographics and social determinants of health on surgical follow-up and complications after medial orbital wall decompression (MOWD) secondary to thyroid associated orbitopathy (TAO). Demographics and social determinants of health (age, sex, race, insurance status) for 46 patients undergoing MOWD secondary to TAO were correlated with post-operative compliance and surgical complications by chi-square analyses. Among 46 patients, 23 were compliant with follow-up. There was no statistically significant difference between compliance and non-compliance based on age (60.25 vs 56.4, p = .41), sex (71.9 % female vs 85.7 % female, p = .31), race (65.6 % white vs 71.4 % white, p = .70) or insurance status (59.4 % private vs 42.9 % private, p = .30). Complications were noted in 50 % of patients of which sinus infection was most common (47.8 % of complications) and epistaxis rare (4.3 % of complications). No correlation was noted between development of complications and compliance (p = .20). Likewise, age, race and insurance status did not correlate with complications. For patients undergoing MOWD, no correlations with compliance or complication rate were noted with age, sex, race, or insurance status. A larger cohort may be indicated to identify such patterns. The overall complication rate was 50 % and the increased number of visits may have economic impact. This study provides a unique chance to assess demographic correlates of compliance and complication while controlling for surgeon preference. There was no association between sociodemographics and compliance or complications.


Anatomical study of type classification and surface area of attachment sites for tibialis anterior tendon.
The purpose of this study was to clarify the attachment types of the tibialis anterior tendon (TAT) in Japanese fixed cadavers and to determine the attachment site area in three dimensions. We examined 100 feet from 50 Japanese cadavers. The TAT was classified according to differences in the number of fiber bundles as: Type I, with one fiber bundle; Type II, with two fiber bundles; and Type III, with three fiber bundles. The attachment site area of the TAT was measured using a three-dimensional scanner. Cases were Type II in 95% and Type III in 5%, with no cases of Type I identified. In Type II, mean attachment site areas were 85.2 ± 18.2 mm2 for the medial cuneiform bone (MCB) and 72.4 ± 19.0 mm2 for the first metatarsal bone (1 MB), showing a significantly larger area for MCB than for 1 MB. These findings suggest the possibility of ethnic differences in TAT attachment types and suggest that TAT attachments in Japanese individuals are highly likely to be Type II, with rare cases of Type III. Accurate measurement of attachment site areas is possible with appropriate three-dimensional measurements.


Na/H exchange activities in NHE1-transfected OK-cells: cell polarity and regulation.
The human fibroblast, "amiloride-sensitive" Na/H exchanger (NHE1) was transfected into opossum kidney cells (OK cells) (OK/NHE1 cells). Northern blot analysis confirmed that the NHE1 message is expressed in OK/NHE1 cells. In immunoblot analysis, an anti-human NHE1 antibody labelled a membrane protein only present in OK/NHE1 cells. In contrast to the parental cell line containing only an apically located, "amiloride-resistant" Na/H exchange activity, OK/NHE1 cells contain apically and basolaterally located Na/H exchange activities, the apical activity being "amiloride resistant" and the basolateral being "amiloride sensitive". Parathyroid hormone (PTH) inhibited apical transport activity (OK and OK/NHE1 cells) but had no effect on basolateral transport activity (OK/NHE1 cells). Pharmacological activation of protein kinase A (forskolin) decreased both apical and basolateral Na/H exchange activity. Incubation with phorbol ester (exogenous activation of protein kinase C) reduced apical Na/H exchange activity (OK and OK/NHE1 cells) but had only a moderate, inhibitory effect on basolateral Na/H exchange activity (OK/NHE1 cells). These results indicate that transfection of OK cells with human fibroblast NHE1 cDNA encoding an "amiloride-sensitive" form of the Na/H exchanger results in expression of basolaterally located "NHE1-related" transport activity. Regulatory control of intracellular Na/H exchange activities (apically versus basolaterally located) and intercellular Na/H exchange activities (NHE1-related) differs. This may relate to cell-specific properties as well as to exchanger-specific properties.


[The use of computers for the interpretation and analysis of teleroentgenograms of the skull].
Software was designed suitable for detection of facial soft tissues contours and reading the anthropometric reference points with their plotting and calculation of angular, linear and indexed teleroentgenographic parameters. These were compared to normal data to determine their percent deviation.


Magnesium ions in catecholamine fluorescence histochemistry. Application to the cryostat and vibratome techniques.
The effects of high concentrations of magnesium ions in the cryostat and Vibratome procedures for visualization of catecholamine fluorescence in the central nervous system have been investigated. In cryostat sections, obtained from specimens perfused with a formaldehyde and glyoxylic acid containing buffer, the addition of high concentrations of MgSO4 to the perfusion solution enhances the fluorescence intensity and reduces the unspecific background fluorescence and the diffusion of the catecholamine fluorophore. This improves the visualization of all portions of the central catecholamine-containing neurons. Similar effects are obtained in the formaldehyde-Vibratome technique by the introduction of an immersion bath containing MgSO4 after the sectioning procedure. The use of the magnesium perfusion or immersion steps furthermore increases the reproducibility of the Vibratome and cryostat techniques. The paper describes the improved Vibratome and cryostat techniques used in our laboratory.


Diagnostic reasoning strategies and diagnostic success.
Cognitive psychology research supports the notion that experts use mental frameworks or "schemes", both to organize knowledge in memory and to solve clinical problems. The central purpose of this study was to determine the relationship between problem-solving strategies and the likelihood of diagnostic success. Think-aloud protocols were collected to determine the diagnostic reasoning used by experts and non-experts when attempting to diagnose clinical presentations in gastroenterology. Using logistic regression analysis, the study found that there is a relationship between diagnostic reasoning strategy and the likelihood of diagnostic success. Compared to hypothetico-deductive reasoning, the odds of diagnostic success were significantly greater when subjects used the diagnostic strategies of pattern recognition and scheme-inductive reasoning. Two other factors emerged as independent determinants of diagnostic success: expertise and clinical presentation. Not surprisingly, experts outperformed novices, while the content area of the clinical cases in each of the four clinical presentations demonstrated varying degrees of difficulty and thus diagnostic success. These findings have significant implications for medical educators. It supports the introduction of "schemes" as a means of enhancing memory organization and improving diagnostic success.


Solubilization and partial characterization of rat liver squalene epoxidase.
The microsomal enzyme system from rat liver which catalyzes squalene epoxidation requires a supernatant protein and phospholipids (Tai, H., and Bloch, K. (1972) J. Biol. Chem. 247, 3767). It has now been found that these two cytoplasmic components can be replaced by Triton X-100. The same detergent solubilizes the microsomal squalene epoxidase and the resulting supernatant can be separated into two components, A and B, by DEAE-cellulose chromatography. Neither Fraction A nor B alone has significant squalene epoxidase activity but combining the two affords a reconstituted system 5-fold higher in specific epoxidase activity than that of the original microsomes. FAD and Triton X-100 in addition to molecular oxygen and NADPH are required in the reconstituted system. Subjecting Fraction A to a second DEAE-cellulose chromatography does not change its specific activity but lowers NADH-ferricyanide reductase activity and the protoheme content to 1/25 and 1/4, respectively. When Fraction B was chromatographed on Sephadex G-200, the specific epoxidase activity tested in the presence of Fraction A was increased 3-fold. This procedure also raised the specific activity of NADPH-cytochrome c reductase activity in Fraction B 3-fold. The reconstituted epoxidase system is not inhibited by either carbon monoxide, potassium cyanide, or o-phenanthrolien but Tiron at 1 mM was inhibitory (50%). Erythrocuprein has no effect on epoxidation. No evidence has been found for the participation of hemoproteins (P450 or cytochrome b5) in squalene epoxidation. Component B appears to be identical with the flavoprotein NADPH-cytochrome c reductase. Component A may be a flavoprotein with an easily dissociable prosthetic group.


Emergence of t(3;21)(q26.2;q22) during eltrombopag treatment in a patient with relapsed aplastic anemia who received chemotherapy for angioimmunoblastic T-cell lymphoma.
A 65-year-old man with nonsevere aplastic anemia received rabbit anti-thymocyte globulin and cyclosporine and partially responded. Six months after the initiation of treatment, he was diagnosed with stage IV angioimmunoblastic T-cell lymphoma and received chemotherapy. PET/CT scan analysis indicated a complete response. However, he showed sustained myelosuppression and was diagnosed with relapse of aplastic anemia. He did not respond to cyclosporine, eltrombopag or methenolone. Fifteen months after eltrombopag administration, he developed MDS with t(3;21)(q26.2;q22). Patients should be monitored carefully for the emergence of not only -7/del(7q) but also 3q26 abnormalities, including t(3;21)(q26.2;q22), during and after eltrombopag treatment.


Inverse regulation of spore germination and growth by cyclic AMP in Streptomyces hygroscopicus.
The cyclic AMP level in germinating spores of Streptomyces hygroscopicus rises to a miximum ag outgrowth of germ tubes. Exogenous cyclic AMP results in an inverse effect on germination speed and growth.


Diagnosis and classification of the periodontal diseases.
A classification for gingivitis and periodontitis has been proposed based on clinical observations and immunologic parameters (summarized in Table 10). Overlapping clinical situations and exceptions to the rule certainly exist and pose challenges to clinicians during diagnosis, prognosis, and treatment planning. The clinical significance of making the diagnosis of either rapidly progressive periodontitis, juvenile, or prepubertal forms of periodontitis compared with adult periodontitis must be considered. A diagnosis of early-onset disease may (1) modify the periodontal treatment plan and may include the use of systemic antibiotics (for example, tetracyclines) or antiplaque agents (for example, sanguinarine, chlorhexidine); (2) modify the prosthetic treatment plan and require longer periods of monitoring before extensive replacement or splinting is initiated; (3) increase the frequency of periodontal recall appointments (at least four to six times during the first year or two following peridontal therapy); (4) implicate a genetic basis for the disease with the possibility of peridontal involvement of other family members; (5) influence decisions on prognosis; and (6) alert the clinician for potential future rapid periodontal breakdown. Future studies will further define and characterize all forms of periodontal diseases. Clinical, microbial, and immunologic information may permit inclusion of the relatively rare forms of periodontitis such as ANUG periodontitis and refractory periodontitis. Understanding the underlying biologic mechanisms of the pathogenesis of the periodontal diseases, coupled with clinical observations, will permit improved clinical investigations that ultimately will improve therapeutic approaches.


Analytical performance of the Roche LightCycler® Mycobacterium Detection Kit for the diagnosis of clinically important mycobacterial species.
The LightCycler® Mycobacterium Detection Kit based on real-time PCR technology for the detection of Mycobacterium tuberculosis, Mycobacterium avium and Mycobacterium kansasii was recently developed. This study evaluated its analytical sensitivity, specificity and reproducibility. Plasmid standards were prepared and used to determine the limit of detection. The assay was also performed against organisms other than mycobacteria, other mycobacterial strains and interfering substances to exclude cross-reactivity and interference. Reference standards were prepared and tested to assess the assay's reproducibility. All PCR assays were performed using the LightCycler® 2.0 Instrument. The detection limit for M. tuberculosis was 28 copies per microlitre. Neither cross-reactivity nor interference occurred with non-mycobacterial organisms and substances tested. Overall reproducibility for consecutive measurements, run-to-run, lot-to-lot, day-to-day and laboratory-to-laboratory achieved a coefficient of variance of less than two percent. The LightCycler® Mycobacterium Detection kit has shown to be a robust and accurate assay with the potential to be used as a rapid TB diagnostic test.


A population-normalized tractographic fiber atlas of the anterior limb of the internal capsule: relevance to surgical neuromodulation.
The anterior limb of the internal capsule (ALIC) is a white matter highway that connects several subcortical structures to the prefrontal cortex. Although surgical interventions in the ALIC have been used to treat a number of psychiatric illnesses, there is significant debate regarding what fibers are targeted for intervention. This debate is partially due to an incomplete understanding of connectivity in the region. To better understand this complex structure, the authors employed a novel tractography-based approach to examine how fibers from the thalamus and subthalamic nucleus (STN) traverse the ALIC. Furthermore, the authors analyzed connections from the medial dorsal nucleus, anterior nucleus, and ventral anterior nucleus of the thalamus. The results showed that there is an organizational gradient of thalamic fibers medially and STN fibers laterally in the ALIC that fades more anteriorly. These findings, in combination with the known corticotopic organization described by previous studies, allow for a more thorough understanding of the organization of the white matter fibers in the ALIC. These results are important for understanding and targeting of neuromodulatory therapies in the ALIC and may help explain why differences in therapeutic effect are observed for different areas of the ALIC.


Prehospital versus hospital fibrinolytic therapy using automated versus cardiologist electrocardiographic diagnosis of myocardial infarction: abortion of myocardial infarction and unjustified fibrinolytic therapy.
This study investigated the incidence of abortion of myocardial infarction and of unjustified fibrinolysis by using automated versus cardiologist-assisted diagnosis of acute ST-elevation myocardial infarction. The results of prehospital diagnosis and treatment (2 cities in the Netherlands) were compared with those of inhospital treatment. Unjustified fibrinolysis must be differentiated from justified thrombolysis resulting in aborted myocardial infarction. Both have the absence of a significant rise in cardiac enzymes in common. In aborted myocardial infarction, this is a result of timely reperfusion; in unjustified thrombolysis, this is the result of an incorrect diagnosis. In the city of Rotterdam, 118 patients were treated before hospitalization for myocardial infarction, diagnosed through the use of a mobile computer electrocardiogram; in the city of Nijmegen, 132 patients were treated before hospitalization with the use of transtelephonic transmission of the electrocardiogram to the coronary care unit and judged by a cardiologist. Their data were compared with those of 269 patients treated inhospital in the city of Arnhem, using the same electrocardiographic criteria. Abortion of myocardial infarction was diagnosed as the absence of a significant rise in cardiac enzymes and the presence of resolution of chest pain and 50% of ST-segment deviation within 2 hours after onset of therapy. Lacking these, the diagnosis of unjustified fibrinolytic therapy was made. Unjustified treatment occurred in 8 (3.2%) prehospital-treated patients (4 in Rotterdam and 4 in Nijmegen). Of the inhospital-treated patients in Arnhem, 5 (1.9%) were treated unjustifiably (P =.49). Aborted myocardial infarction occurred in 15.3% and 18.2% in Rotterdam and Nijmegen, respectively, against 4.5% in inhospital treatment in Arnhem (P <.001). Abortion of myocardial infarction is associated with prehospital thrombolysis. Unjustified fibrinolysis for acute myocardial infarction occurs in prehospital fibrinolysis as frequently as in the inhospital setting. The use of different electrocardiographic methods for diagnosing acute myocardial infarction does not appear to make any difference.


Current status of zirconia implants in dentistry: preclinical tests.
This systematic review aimed to provide an overview of zirconia implants as well as regarding the outcome of the implant-restorative complex in preclinical studies. An electronic search of the literature prior to July 2017 was performed to identify all articles related to preclinical research on zirconia implants. The search was conducted using MEDLINE (National Library of Medicine) and PubMed without restrictions concerning the date of publication. The search terminology included: zirconia implant, osseointegration, bone-to-implant contact, soft tissue, histology, histomorphometry, surface modification, surface roughness, surface characteristics, and restoration (connecting multiple keywords with AND, OR). Fifty-seven studies were finally selected from an initial yield of 654 titles, and the data were extracted. The identified preclinical studies focused on several aspects related to zirconia implants, namely biocompatibility, mechanical properties, implant design, osseointegration capacity, soft tissue response, and restorative options. Due to heterogeneity of the studies, a meta-analysis was not possible. The most frequently used zirconia material for the fabrication of implants is yttria-stabilized tetragonal zirconia polycrystal. The resistance-to-fracture for zirconia implants ranged between 516-2044N. The mostly investigated parameter was osseointegration, which is compared to that of titanium. A lack of evidence was found with other parameters. Due to its good biocompatibility as well as favorable physical and mechanical properties, zirconia implants are a potential alternative to titanium implants. However, knowledge regarding the implant-restorative complex and related aspects is still immature to recommend its application for daily practice.


Channel catfish immunoglobulins: repertoire and expression.
The channel catfish, Ictalurus punctatus, is widely recognized as an important model for studying immune responses in ectothermic vertebrates. It is one of the few fish species for which defined viable in vitro culture systems have been established and is currently the only fish species from which a variety of functionally distinct clonal leukocyte lines are available. Moreover, there is a large basis of biochemical and molecular information on the structure and function of catfish immunoglobulins (Igs). Catfish, as other teleosts, have a tetrameric homolog of IgM as their predominant serum Ig plus a homolog of IgD. They also have genetic elements basically similar to those of mammals, which encode and regulate their expression. The catfish Ig heavy (H) chain locus is a translocon-type locus with three Igdelta genes linked to an Igmu gene or pseudogene. The catfish IgH locus is estimated to contain approximately 200 variable (V) region genes representing 13 families as well as at least three diversity (D) and 11 joining (JH) genes. The catfish has two light (L) chain isotypes, F and G, both encoded by loci organized in multiple cassettes of VL-JL-CL with the VL in the opposite transcriptional orientation. Hence, all requisite components for encoding antibodies are present in the catfish, albeit with certain variations. In the future, whether or not additional unique features of Ig function and expression will be found remains to be determined.


The biology of chikungunya: a brief review of what we still do not know.
Responsible for a massive outbreak in the Indian Ocean in 2005-2006, the chikungunya virus is also reemerging in India where it has already infected over a million persons. Imported cases of the disease are reported in Asia, USA, and Europe, where a small epidemic occurred, due to transmission by local mosquitoes. Chikungunya virus is an alphavirus (Togaviridae family) that usually induces an acute illness characterized by fever, rash, and painful, incapacitating arthralgia a few days after being bitten by an infected mosquito, but recurrent joint pains are frequent. Unusual severe forms of the disease are also being reported that emphasize the importance of close monitoring of arboviruses in more fragile populations, such as the elderly and the newborns. Alphaviruses have generally been studied out of their epidemic context, leading to a large knowledge of their molecular features, and a much narrower understanding of their epidemiology and induced pathogenesis. Deciphering chikungunya virus specific molecular features as well as how the virus interacts with its vector and with its host are key to foresee, prevent and manage future epidemics, as well as prevent, treat or cure chikungunya disease.


Accuracy of intracranial pressure monitoring: systematic review and meta-analysis.
Intracranial pressure (ICP) measurement is used to tailor interventions and to assist in formulating the prognosis for traumatic brain injury patients. Accurate data are therefore essential. The aim of this study was to verify the accuracy of ICP monitoring systems on the basis of a literature review. A PubMed search was conducted from 1982 to 2014, plus additional references from the selected papers. Accuracy was defined as the degree of correspondence between the pressure read by the catheter and a reference "real" ICP measurement. Studies comparing simultaneous readings from at least two catheters were included. Drift was defined as the loss of accuracy over the monitoring period. Meta-analyses of data from the studies were used to estimate the overall mean difference between simultaneous ICP measurements and their variability. Individual studies were weighted using both a fixed and a random effects model. Of 163 articles screened, 83 compared two intracranial catheters: 64 reported accuracy and 37 drift (some reported both). Of these, 10 and 17, respectively, fulfilled the inclusion criteria for accuracy and zero drift analysis. The combined mean differences between probes were 1.5 mmHg (95 % confidence interval (CI) 0.7-2.3) with the random effects model and 1.6 mmHg (95 % CI 1.3-1.9) with the fixed effects model. The reported mean drift over a long observation period was 0.75 mmHg. No relation was found with the duration of monitoring or differences between various probes. This study confirms that the average error between ICP measures is clinically negligible. The random effects model, however, indicates that a high percentage of readings may vary over a wide range, with clinical implications both for future comparison studies and for daily care.


Massive rotator cuff tears: pathomechanics, current treatment options, and clinical outcomes.
Rotator cuff tear size has an important effect on clinical outcomes after repair. Management options for massive rotator cuff tears are numerous, and selection of the most appropriate treatment method for individual patients can be a challenge. An understanding of the pathomechanics, treatment, and clinical outcomes in patients with massive rotator cuff tears can serve as a guide for clinical decision-making. The purpose of this article was to review treatment options and clinical outcomes for the management of massive rotator cuff tears.


Experimental analysis of lead-in-air sources in lead-acid battery manufacture.
Plant-scale experimental sampling programs were carried out to determine the contribution to the lead-in-air exposure from (a) fork-truck transport of pasted plates in racks and (b) manual loading and unloading of plates from racks. Fork-truck transport was found not significant under "clean" conditions. Manual loading and unloading was found significant.


Human APC sequesters beta-catenin even in the absence of GSK-3beta in a Drosophila model.
There have been conflicting reports on the requirement of GSK-3beta-mediated phosphorylation of the tumor suppressor adenomatous polyposis coli (APC) vis-à-vis its ability to bind and degrade beta-catenin. Using a unique combination of loss of function for Shaggy/GSK-3beta and a gain of function for human APC in Drosophila, we show that misexpressed human APC (hAPC) can still sequester Armadillo/beta-catenin. In addition, human APC could suppress gain of Wnt/Wingless phenotypes associated with loss of Shaggy/GSK-3beta activity, suggesting that sequestered Armadillo/beta-catenin is non-functional. Based on these studies, we propose that binding per se of beta-catenin by APC does not require phosphorylation by GSK-3beta.


Role of G-protein coupled receptor kinase 5 gene in cognitive impairment in Parkinson's disease.
The objective of our study was to investigate the association of two single nucleotide polymorphisms (SNPs) with genetic risk of dementia. In 212 patients with Parkinson's disease (PD), we investigated two polymorphisms within the G-protein coupled receptor kinase 5 (GRK5) gene (rs2420616, rs4752293) to determine a possible risk factor for dementia. We identified two alleles most significantly present in PD patients with dementia: G and T alleles. We also identified risk haplotypes: GC, and AT. We demonstrated that the SNPs and the related haplotypes could play a central role in predisposing PD patients to cognitive impairment.


The Maternal-to-Zygotic Transition in Higher Plants: Available Approaches, Critical Limitations, and Technical Requirements.
Fertilization marks the turnover from the gametophyte to sporophyte generation in higher plants. After fertilization, sporophytic development undergoes genetic turnover from maternal to zygotic control: the maternal-to-zygotic transition (MZT). The MZT is thought to be critical for early embryogenesis; however, little is known about the time course or developmental impact of the MZT in higher plants. Here, we discuss what is known in the field and focus on techniques used in relevant studies and their limitations. Some significant questions and technical requirements for further investigations are also discussed.


Coxiella and Bartonella spp. in bats (Chiroptera) captured in the Brazilian Atlantic Forest biome.
The role of bats as reservoirs of zoonotic agents, especially pathogenic bacteria such as Bartonella and Coxiella, has been discussed around the world. Recent studies have identified bats as potential hosts of species from the proteobacteria phylum. In Brazil, however, the role of bats in the natural cycle of these agents is poorly investigated and generally neglected. In order to analyze the participation of bats in the epidemiology of diseases caused by Bartonella, Coxiella, Rickettsia, Anaplasma and Ehrlichia, we conducted a descriptive epidemiological study in three biogeographic regions of the Brazilian Atlantic Forest. Tissues of 119 bats captured in preserved areas in the states of Rio de Janeiro, Bahia and Santa Catarina from 2014 to 2015 were submitted to molecular analysis using specific primers. Bartonella spp. was detected in 22 spleen samples (18.5%, 95% CI: 11.9-26.6), whose phylogenetic analysis revealed the generation of at least two independent clusters, suggesting that these may be new unique genotypes of Bartonella species. In addition, four samples (3.4%, 95% CI: 0.9-8.3) were positive for the htpAB gene of C. burnetii [spleen (2), liver (1) and heart (1)]. Rickettsia spp., Anaplasma and Ehrlichia were not identified. This is the first study reporting C. burnetii and Bartonella spp. infections in bats from the Atlantic Forest biome. These findings shed light on potential host range for these bacteria, which are characterized as important zoonotic pathogens.


Oral corticosteroids in the management of chronic rhinosinusitis with and without nasal polyps: Risks and benefits.
Oral steroids are synthetic mimics of adrenal cortex hormones and are considered a staple in the management of chronic rhinosinusitis due to their anti-inflammatory effects. Despite their common use, many providers are not familiar with the potential risks of the drugs. Literature review. An overview of the existing data on the risks of oral steroids is presented as well as a review of the malpractice lawsuits with regard to oral steroid use and a discussion of the data that support the use of oral steroids in patients with chronic rhinosinusitis with and those without nasal polyps. It is essential for providers to be aware of the potential complications of a medication, the medical jurisprudence of the drugs, and the data that support their use.


Analytical Considerations When Anchoring Discrete Choice Experiment Values Using Composite Time Trade-Off Data: The Case of EQ-5D-Y-3L.
Discrete choice experiments (DCEs) are becoming increasingly used to elicit preferences for children's health states. However, DCE data need to be anchored to produce value sets, and composite time trade-off (cTTO) data are typically used in the context of EQ-5D-Y-3L valuation. The objective of this paper is to compare different anchoring methods, summarise the characteristics of the value sets they produce, and outline key considerations for analysts. Three anchoring methods were compared using data from published studies: (1) rescaling using the mean value for the worst health state; (2) linear mapping; and (3) hybrid modelling. The worst state rescaling value set had the largest range. The worst state rescaling and linear mapping value sets preserved the relative importance of the dimensions from the DCE, whereas the hybrid model value set did not. Overall, the predicted values from the hybrid model value set were more closely aligned with the cTTO values. These findings are relatively generalisable. Deciding upon which anchoring approach to use is challenging, as there are numerous considerations. Where cTTO data are collected for more than one health state, anchoring on the worst health state will arguably be suboptimal. However, the final choice of approach may require value judgements to be made. Researchers should seek input from relevant stakeholders when commencing valuation studies to help guide decisions and should clearly set out their rationale for their preferred anchoring approach in study outputs.


Transmission of simian immunodeficiency virus carrying multiple cytotoxic T-lymphocyte escape mutations with diminished replicative ability can result in AIDS progression in rhesus macaques.
Cytotoxic T-lymphocyte (CTL) responses frequently select for immunodeficiency virus mutations that result in escape from CTL recognition with viral fitness costs. The replication in vivo of such viruses carrying not single but multiple escape mutations in the absence of the CTL pressure has remained undetermined. Here, we have examined the replication of simian immunodeficiency virus (SIV) with five gag mutations selected in a macaque possessing the major histocompatibility complex haplotype 90-120-Ia after its transmission into 90-120-Ia-negative macaques. Our results showed that even such a "crippled" SIV infection can result in persistent viral replication, multiple reversions, and AIDS progression.


Identification and characterization of proteins, lipids, and metabolites in two organic fertilizer products derived from different nutrient sources.
The biochemical composition of organic fertilizers largely determines their nutrient supply characteristics following soil application as well as their potential impact on soil microbial communities. Yet, limited information is available regarding the biochemical composition of organic fertilizers derived from different nutrient sources. Here, we qualitatively analyzed the presence and abundance of proteins, lipids, and metabolites in a liquid fish fertilizer (LFF) product and a type of granular organic fertilizer (GOF) commonly used in organic vegetable production, using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Our results suggest that the presence and abundance of proteins, lipids, and metabolites differ greatly between GOF and LFF. The qualitative analysis shows LFF as a rich source of metabolites, while complex proteins and long-chain saturated fatty acids are dominant in GOF. The degree of biochemical composition complexity may help explain the varying impacts of different types of organic fertilizers on nutrient availability, soil health, and environmental quality. The online version contains supplementary material available at 10.1186/s13765-021-00625-2.


Specific immunostaining of CCK cells by use of synthetic fragment antisera.
Antibodies to the central fragments 9-20 dodecapeptide sequence of CCK were used for specific immunostaining of the CCK cells of the mammalian gut. The use of high specific antibodies to synthetic fragment, essential when there is a possibility of immunochemical cross reactions between antisera and hormones of similar molecular structure provides the key to increased understanding of the nature and relationships of peptide hormones.


[Report on difficulty in blood group identification due to anti-H antibody in three cases].
Anti-H antibody belongs to IgM type cold antibody, which often induces the unconformity of positive and reverse typing and leads to the difficulty in clinical blood typing. Anti-H antibody was found during identification of the counter blood group in 3 cases. The antibody was found to be active at 37 degrees C, room temperature and 4 degrees C when determined by blood group serology, and was finally analyzed to be IgM. It is suggested that not to give erythrocytes of O group unreasoningly to blood recipient of AB group during emergent moment, but instead, to give same type of blood. If there was no same type of blood during urgent events, O type erythrocytes could be employed after being matched by saline centrifuging with host side coincidence and screened by incomplete method. In this case, anti-H antibody leading to adverse-reaction in blood transfusion should be prevented.


Pathways of secretion in the exocrine pancreas: the status of resting secretion.
In the last decade the concept of two distinct pathways of secretion in the exocrine pancreas has slowly emerged. According to this concept, one pathway is involved in stimulated (regulated) conditions and another under resting (constitutive) conditions. This hypothesis was elaborated at first from the comparison of the specific radioactivities of secretory proteins released by the gland under resting and stimulated conditions. Analysis of the protein composition of the juice released under these two physiological conditions further supported that hypothesis. More recent studies compared the kinetic of accumulation of newly synthesized proteins in zymogen granule and their release in the gland lumen. The latter results are in agreement with a model in which secretory proteins are channelled in two separate pathways, one regulated, and one constitutive. Essentially, the constitutive pathway would correspond to a paragranular route in which the proteins would be immediately secreted instead of being stored in zymogen granules. In addition, some of the proteins released in the juice under "resting" conditions are associated to microvesicles. The term "microvesicular secretion" is used to designate that type of secretion.


Leishmania interaction with human monocytes and neutrophils: modulation of the chemotactic response.
Infection of host cells with Leishmania, which are obligate parasites of mononuclear phagocytes, most probably involved chemotaxis of host cells towards the parasite. We have examined the chemotactic properties of a sonicate derived from L. mexicana amazonensis promastigotes for normal human peripheral blood monocytes and neutrophils. L. m. amazonensis sonicate exhibited chemotactic activity for monocytes and neutrophils. Treatment at 65 degrees C for 30 min, enhanced the activity for neutrophils but not for monocytes, while treatment at 100 degrees C for 60 min abolished the activity. Additional studies showed that the sonicate generated chemotactic activity in serum, presumably by activating the alternative complement pathway to produce C5a, for monocytes and neutrophils. Incubation of monocytes and neutrophils with the sonicate inhibited the chemotactic activity of these cells towards various chemoattractants. When the sonicate was heat-treated the inhibitory effect was lost, except when sonicate was used as a chemoattractant. These results indicate the presence of specific receptors for factor(s) from L. m. amazonensis promastigotes on human monocytes and neutrophils.


Higher mitochondrial oxidative capacity is the primary molecular differentiator in muscle of rats with high and low intrinsic cardiorespiratory fitness.
Cardiorespiratory fitness (CRF) is tightly linked with health and longevity and is implicated in metabolic flexibility and substrate metabolism. The high capacity runner (HCR) and low capacity runner (LCR) rat lines are a genetically heterogeneous rat model selected and bred for CRF that reflect CRF in humans by exhibiting differences in nutrient handling. This study aims to differentiate the intrinsic substrate preference of the HCR compared to LCR rats to better understand the intersection of mitochondrial respiration and intrinsic CRF. We performed bulk skeletal muscle RNA-Sequencing on male and female HCR and LCR rats and assessed the effect of rat line on mitochondrial gene expression pathways using the MitoCarta3.0 database. In a separate cohort of rats, mitochondria were isolated from skeletal and cardiac muscle and maximal oxidation rates were measured using an Oroboros O2k when provided either pyruvate or fatty acid substrates. The expression of mitochondrial genes are significantly upregulated in HCR skeletal muscle in both male and female rats. In respirometry experiments, fatty acid oxidative capacities were greater in HCR compared to LCR, and male compared to female rats, as a function of both mitochondrial quality and mitochondrial density. This effect was greater in the skeletal muscle than in the heart. Pyruvate oxidation did not differ significantly between lines. The capacity for increased fatty acid oxidation in the HCR rat is a result of selection for running capacity and is likely a key contributor to the healthy metabolic phenotype of individuals with high CRF.


Artificial intelligence guided HRCT assessment predicts the severity of COVID-19 pneumonia based on clinical parameters.
The purpose of the study was to compare the results of AI (artificial intelligence) analysis of the extent of pulmonary lesions on HRCT (high resolution computed tomography) images in COVID-19 pneumonia, with clinical data including laboratory markers of inflammation, to verify whether AI HRCT assessment can predict the clinical severity of COVID-19 pneumonia. The analyzed group consisted of 388 patients with COVID-19 pneumonia, with automatically analyzed HRCT parameters of volume: AIV (absolute inflammation), AGV (absolute ground glass), ACV (absolute consolidation), PIV (percentage inflammation), PGV (percentage ground glass), PCV (percentage consolidation). Clinical data included: age, sex, admission parameters: respiratory rate, oxygen saturation, CRP (C-reactive protein), IL6 (interleukin 6), IG - immature granulocytes, WBC (white blood count), neutrophil count, lymphocyte count, serum ferritin, LDH (lactate dehydrogenase), NIH (National Institute of Health) severity score; parameters of clinical course: in-hospital death, transfer to the ICU (intensive care unit), length of hospital stay. The highest correlation coefficients were found for PGV, PIV, with LDH (respectively 0.65, 0.64); PIV, PGV, with oxygen saturation (respectively - 0.53, -0.52); AIV, AGV, with CRP (respectively 0.48, 0.46); AGV, AIV, with ferritin (respectively 0.46, 0.45). Patients with critical pneumonia had significantly lower oxygen saturation, and higher levels of immune-inflammatory biomarkers on admission. The radiological parameters of lung involvement proved to be strong predictors of transfer to the ICU (in particular, PGV ≥ cut-off point 29% with Odds Ratio (OR): 7.53) and in-hospital death (in particular: AIV ≥ cut-off point 831 cm3 with OR: 4.31). Automatic analysis of HRCT images by AI may be a valuable method for predicting the severity of COVID-19 pneumonia. The radiological parameters of lung involvement correlate with laboratory markers of inflammation, and are strong predictors of transfer to the ICU and in-hospital death from COVID-19. National Center for Research and Development CRACoV-HHS project, contract number SZPITALE-JEDNOIMIENNE/18/2020.


Acquired Brain Injuries Across the Perinatal Spectrum: Pathophysiology and Emerging Therapies.
The development of the central nervous system can be directly disrupted by a variety of acquired factors, including infectious, inflammatory, hypoxic-ischemic, and toxic insults. Influences external to the fetus also impact neurodevelopment, including placental health, maternal comorbidities, adverse experiences, environmental exposures, and social determinants of health. Acquired perinatal brain insults tend to affect the developing brain in a stage-specific manner that reflects the susceptible cell types, developmental processes, and risk factors present at the time of the insult. In this review, we discuss the pathophysiology, neurodevelopmental outcomes, and management of common acquired perinatal brain conditions. In the fetal brain, we divide insults based on trimester, and in the postnatal brain, we focus on common pathologies that have a presentation dependent on gestational age at birth: white matter injury and germinal matrix hemorrhage/intraventricular hemorrhage in preterm infants and hypoxic-ischemic encephalopathy in term infants. Although specific treatments for fetal and newborn brain disorders are currently limited, we emphasize therapies in preclinical or early clinical phases of the development pipeline. The growing number of novel cell type- and stage-specific emerging therapies suggests that in the near future we may have a dramatically improved ability to treat acquired perinatal brain disorders and to mitigate the associated neurodevelopmental consequences.


Effect of physiological conditions and biochemical factors of mussels Mytilus galloprovincialis in radioactivity monitoring programs along the Algerian coast.
A study was carried out to determine the activities of radionuclides (137Cs, 40K, 226Ra, 214Bi, 214Pb, and 210Pb) and the levels of biochemical components (lipids, carbohydrates, and proteins) in mussels (Mytilus galloprovincialis) along the Algerian coast. The goal was to evaluate the effect of mussels' biological parameters on radionuclide concentrations, through two coastal water biomonitoring programs. The mussels were taken from three study areas on the Algerian coast: Kristel (Oran), Surcouf (Alger), and Collo (Skikda), for the passive biomonitoring program and transplanted from each study area into the control site of Surcouf. Biochemical components were determined by means of UV-visible colorimetric assays, while the activity concentrations of radionuclides were measured by gamma-ray spectrometry. The results showed that carbohydrates were the most abundant biochemical components (40-60%) compared with proteins (20-40%) and lipids (15-20%). 137Cs activity concentrations were below the lower limit of detection (LOD) for all samples, while the high activities of 40K are the result of its behavior as stabile potassium K which is extensively used in the metabolism of mussels reflects the conditional state of mussels. 210Pb concentration reflects the conditional state of mussels (morphometric parameters and proteins content). The mussels' bioaccumulation capacity for radionuclides was found to be dependent on the growing site and the biomonitoring time period.


Outcome comparison of 600- and 300-mg loading doses of clopidogrel in patients undergoing primary percutaneous coronary intervention for ST-segment elevation myocardial infarction: results from the ARMYDA-6 MI (Antiplatelet therapy for Reduction of MYocardial Damage during Angioplasty-Myocardial Infarction) randomized study.
The purpose of this study was to compare 600- and 300-mg clopidogrel loading doses in patients with ST-segment elevation myocardial infarction (STEMI). Given the high thrombotic risk of patients with STEMI, greater platelet inhibition may improve outcome in those patients receiving percutaneous coronary intervention (PCI). Although observational data suggest that pretreatment with a 600-mg clopidogrel loading dose may be more effective than the 300-mg regimen in primary PCI, this hypothesis has never been tested in a randomized study. A total of 201 patients undergoing primary PCI for STEMI randomly received a 600-mg (n = 103) or 300-mg (n = 98) clopidogrel loading dose before the procedure. The primary endpoint was the evaluation of the infarct size, defined as the area under the curve of cardiac markers. Infarct size was significantly lower in the high-dose regimen: median creatine kinase-myocardial band 2,070 ng/ml (interquartile range [IQR]: 815 to 2,847 ng/ml) versus 3,049 ng/ml (IQR: 1,050 to 7,031 ng/ml) in the 300-mg group, p = 0.0001; troponin-I 255 ng/ml (IQR: 130 to 461 ng/ml) versus 380 ng/ml (IQR: 134 to 1,406 ng/ml), p < 0.0001. In the 600-mg arm, Thrombolysis In Myocardial Infarction flow grade <3 after PCI was less frequent (5.8% vs. 16.3%, p = 0.031), left ventricular ejection fraction at discharge was improved (52.1 ± 9.5% vs. 48.8 ± 11.3%, p = 0.026), 30-day major adverse cardiovascular events were fewer (5.8% vs. 15%, p = 0.049), and bleeding/entry site complications were not increased (secondary endpoints). In STEMI patients, pre-treatment with a 600-mg clopidogrel loading dose before primary PCI was associated with a reduction of the infarct size compared with a 300-mg loading dose, as well as with improvement of angiographic results, residual cardiac function, and 30-day major adverse cardiovascular events; further studies are warranted to evaluate impact of such strategy on survival.


Pubertal delay as an aid in diagnosis and treatment of a transsexual adolescent.
Early cross-sex hormonal interventions (that is, between 16 and 18) as a treatment for young transsexuals are often considered to be risky. However, the delay of such treatment until after the development of secondary sex characteristics has obvious drawbacks for transsexual individuals. This paper reports a postoperative follow-up case-study of a female-to-male transsexual who was treated with a combination of an LHRH agonist (which delayed her secondary sex characteristics development) and psychotherapy at age 13, and subsequently underwent sex reassignment at 18.


Palliative Medicine Consultation Reduces Length of Stay, Improves Symptom Management, and Clarifies Advance Directives in the Geriatric Trauma Population.
The impact of Palliative Medicine Consultation (PMC) on geriatric trauma patients' outcomes was evaluated. It was hypothesized that patients with PMC would have a shorter length of stay. Patients aged 65 years or older and admitted to trauma services were analyzed. Patients with a PMC were more likely to have a documented advance directive discussion (P < .001) and a code status update (P < .001). Length of stay was reduced for patients with a PMC on or before trauma day 2 compared to those with a PMC after trauma day 2. Palliative Medicine should be consulted early into a geriatric patient's hospital stay.


Encopresis and constipation in children.
Chronic retentive constipation in children is common, often undertreated, and frequently resistant to standard treatment. A new understanding of abnormal defecation dynamics has evolved to complement the established medical behavior model of this condition. The primary care pediatrician is in an excellent position to facilitate prevention through counseling on normal bowel habits and early intervention. A comprehensive medical behavior intervention program can be supervised effectively by the pediatrician providing benefit to most patients. Those who are compliant with treatment and are resistant to intervention may benefit by extensive evaluation of anorectal dynamics and use of such teaching as biofeedback training.


A bifunctional α-amylase/trypsin inhibitor from pigeonpea seeds: Purification, biochemical characterization and its bio-efficacy against Helicoverpa armigera.
This paper evaluates α-amylase inhibitor (α-AI) mediated defense of pigeonpea against Helicoverpa armigera. A bifunctional α-amylase/trypsin inhibitor was purified from the seeds of pigeonpea by native liquid phase isoelectric focusing (N-LP-IEF), affinity chromatography and preparative electrophoresis. Its in-vivo and in-vitro interaction with midgut amylases of H. armigera was studied along with growth inhibitory activity. One and two dimensional (2D) zymographic analyses revealed that the purified inhibitor is dimeric glycoprotein (60.2kDa and 56kDa) exist in a multi-isomeric form with five pI variants (pI 5.5 to 6.3). It was found to be heat labile with complete inactivation up to 80°C and stable over a wide range of pH (4-11). The slow binding and competitive type of α-amylase inhibition was observed with 0.08μM of dissociation constant (Ki) for the enzyme-inhibitor complex (EI). The internal protein sequence of two subunits obtained by mass spectrometry matched with cereal-type α-AI, a conserved domain from AAI_LTSS superfamily and sialyltransferase-like protein respectively. In-vivo studies indicated up-regulation of total midgut α-amylase activity with negative effect on growth rate of H. armigera suggesting its suitability for pest control.


A novel self-aggregated gold nanoparticles based on sensitive immunochromatographic assays for highly detection of opium poppy in herbal teas.
Opium poppy abused in food has aroused public concerns due to its serious side effects. Effective monitoring is essential to fight the abuse crisis. Herein, we synthesized an easily prepared, affordable, accessible highly aggregated gold nanoparticles (AGNPs) performing in lateral flow immunoassay (LFIA) for detection opium poppy in herbal teas. Simultaneously, a LFIA based ontime-resolved fluorescent microspheres (TRFMs) was developed as contrastive method. In this study, morphine (MOR), codeine (COD) and thebaine (THE) were as the specific recognition markers of opium poppy. Results demonstrated the quantitative limits of detection were 0.0049/0.0053/0.084, 0.034/0.037/0.37 ng mL-1 for AGNPs/TRFMs-LFIA, respectively. The recoveries were 95%-107.5%/91%-106.7% with coefficient of variation was 1.6%-6.6%/1.8%-7.2%, indicating excellent accuracy and precision. Parallel experiments among AGNPs/TRFMs-LFIA and LC-MS/MS analysis showed good correlation. Overall, AGNPs-LFIA executed quantitative analysis within 15 min on the basis of simple treatment while providing a rapid and sensitive analysis strategy for illegal drugs abused.


Viscoelasticity of human descending thoracic aorta in a mock circulatory loop.
Healthy human descending thoracic aortas, obtained during organ donation for transplant and research, were tested in a mock circulatory loop to measure the mechanical response to physiological pulsatile pressure and flow. The viscoelastic properties of the aortic segments were investigated at three different pulse rates. The same aortic segments were also subjected to quasi-static pressure tests in order to identify the aortic dynamic stiffness ratio, which is defined as the ratio between the stiffness in case of pulsatile pressure and the stiffness measured for static pressurization, both at the same value of pressure. The loss factor was also identified. The shape of the deformed aorta under static and dynamic pressure was measured by image processing to verify the compatibility of the end supports with the natural deformation of the aorta in the human body. In addition, layer-specific experiments on 10 human descending thoracic aortas allowed to precisely identify the mass density of the aortic tissue, which is an important parameter in cardiovascular dynamic models.


A co-formulation of interferons alpha2b and gamma distinctively targets cell cycle in the glioblastoma-derived cell line U-87MG.
HeberFERON is a co-formulation of α2b and γ interferons, based on their synergism, which has shown its clinical superiority over individual interferons in basal cell carcinomas. In glioblastoma (GBM), HeberFERON has displayed promising preclinical and clinical results. This led us to design a microarray experiment aimed at identifying the molecular mechanisms involved in the distinctive effect of HeberFERON compared to the individual interferons in U-87MG model. Transcriptional expression profiling including a control (untreated) and three groups receiving α2b-interferon, γ-interferon and HeberFERON was performed using an Illumina HT-12 microarray platform. Unsupervised methods for gene and sample grouping, identification of differentially expressed genes, functional enrichment and network analysis computational biology methods were applied to identify distinctive transcription patterns of HeberFERON. Validation of most representative genes was performed by qPCR. For the cell cycle analysis of cells treated with HeberFERON for 24 h, 48 and 72 h we used flow cytometry. The three treatments show different behavior based on the gene expression profiles. The enrichment analysis identified several mitotic cell cycle related events, in particular from prometaphase to anaphase, which are exclusively targeted by HeberFERON. The FOXM1 transcription factor network that is involved in several cell cycle phases and is highly expressed in GBMs, is significantly down regulated. Flow cytometry experiments corroborated the action of HeberFERON on the cell cycle in a dose and time dependent manner with a clear cellular arrest as of 24 h post-treatment. Despite the fact that p53 was not down-regulated, several genes involved in its regulatory activity were functionally enriched. Network analysis also revealed a strong relationship of p53 with genes targeted by HeberFERON. We propose a mechanistic model to explain this distinctive action, based on the simultaneous activation of PKR and ATF3, p53 phosphorylation changes, as well as its reduced MDM2 mediated ubiquitination and export from the nucleus to the cytoplasm. PLK1, AURKB, BIRC5 and CCNB1 genes, all regulated by FOXM1, also play central roles in this model. These and other interactions could explain a G2/M arrest and the effect of HeberFERON on the proliferation of U-87MG. We proposed molecular mechanisms underlying the distinctive behavior of HeberFERON compared to the treatments with the individual interferons in U-87MG model, where cell cycle related events were highly relevant.