A survey of first-year pathology residents: factors in career choice.
Pathology has become less attractive to US medical graduates by every measure available to us. In 1981, 2.3 per cent of US medical school seniors planned a pathology career; by 1986, a steady decline had reached 1.6 per cent. In absolute numbers, adjusted for the response rate to the AAMC questionnaire, this means that the 290 seniors entering pathology in 1981 had fallen to 205 by 1986. FMGs enter pathology through the matching program in greater numbers than any other specialty. Our data show that slightly less than a third of current first-year pathology residents are FMGs, mainly from Caribbean and Mexican medical schools. The decline in US graduates entering pathology has resulted almost entirely from a drop in the number of men choosing the field. In 1984, 286 male US graduates matched in pathology, but this number dropped to 150 in 1985 and 149 in 1986. The group entering in 1985 was the first who will need 5 years to be eligible for certification in the anatomic pathology/clinical pathology programs. During the same years, the 116 women who matched in 1984 were followed by 111 in 1985 and 100 in 1986. The effect of the American Board of Pathology's change in requirements is not easily analyzed. The figures for residents entering, given above, would suggest that the requirements discouraged men, especially, from entering the field. This hypothesis is supported by our questionnaire data and by anecdote concerning the pressure felt by graduating seniors to finish their postgraduate training as fast as they can and start paying off their average debt of $33,650. Pathology still seems to attract people who like to teach, study interesting case material, and do research. The percentage of PhD/MDs entering pathology is almost 10 times as high as their percentage among graduating seniors. Discouragement against entering pathology came from a perceived shortage of job openings, negative statements from other physicians (including pathologists), the addition of a fifth-year requirement, and lack of patient contact. The last is hard to account for because pathology would obviously not offer the opportunities to see patients that exist in the clinical specialties, but it was prominent in the concerns of residents answering our questionnaire. The picture that emerges from our data is one of a specialty passing through a difficult period in attracting new talent into its ranks. The first step in dealing with the problem would seem to be recognizing its existence.(ABSTRACT TRUNCATED AT 400 WORDS)


Pathogenesis of human leukocyte antigen B27-positive arthritis. Information from clinical materials.
In the spondyloarthropathies human leukocyte antigen (HLA) B27 confers a strong genetic predisposition to the development and to the chronicity of disease after extra-articular infection with certain gram-negative bacteria. The close relationships between infection, HLA-B27, other genetic factors, and the host immune system, however, still are unexplained. HLA-B27-positive arthritis continues to be an area of intensive investigation in basic and clinical research. New animal models with HLA-B27 transgenic mice and rats, as well as recent developments in understanding the processes involved in signal transduction, cytokine production, and human T-lymphocyte activation, contribute to the development of new pathogenic models of the spondyloarthropathies. This article summarizes the current concepts of the cause and pathogenesis of the spondyloarthropathies resulting from studies of clinical materials. The host-microbial interplay in human disease, namely in bacteria-induced reactive arthritis, may eludicate principle disease mechanisms in acute disease and in the development of chronic autoimmune arthritis or ankylosing spondylitis.


Treatment of a patient with Class II malocclusion, impacted maxillary canine with a dilacerated root, and peg-shaped lateral incisors.
The maxillary canines are important teeth in terms of esthetics and function. This case report describes the orthodontic treatment of a 12-year-old girl whose Class II malocclusion was complicated by an impacted maxillary canine and peg-shaped lateral incisors. Despite dilaceration of the root, the impacted canine was brought into alignment. The peg-shaped lateral incisors were extracted, and the spaces were closed, resulting in favorable esthetics and good occlusion in the long term.


Inkoo and Sindbis viruses in blood sucking insects, and a serological study for Inkoo virus in semi-domesticated Eurasian tundra reindeer in Norway.
Mosquito-borne viruses pose a serious threat to humans worldwide. There has been an upsurge in the number of mosquito-borne viruses in Europe, mostly belonging to the families Togaviridae, genus Alphavirus (Sindbis, Chikungunya), Flaviviridae (West Nile, Usutu, Dengue), and Peribunyaviridae, genus Orthobunyavirus, California serogroup (Inkoo, Batai, Tahyna). The principal focus of this study was Inkoo (INKV) and Sindbis (SINV) virus circulating in Norway, Sweden, Finland, and some parts of Russia. These viruses are associated with morbidity in humans. However, there is a knowledge gap regarding reservoirs and transmission. Therefore, we aimed to determine the prevalence of INKV and SINV in blood sucking insects and seroprevalence for INKV in semi-domesticated Eurasian tundra reindeer (Rangifer tarandus tarandus) in Norway. In total, 213 pools containing about 25 blood sucking insects (BSI) each and 480 reindeer sera were collected in eight Norwegian reindeer summer pasture districts during 2013-2015. The pools were analysed by RT-PCR to detect INKV and by RT-real-time PCR for SINV. Reindeer sera were analysed for INKV-specific IgG by an Indirect Immunofluorescence Assay (n = 480, IIFA) and a Plaque Reduction Neutralization Test (n = 60, PRNT). Aedes spp. were the most dominant species among the collected BSI. Two of the pools were positive for INKV-RNA by RT-PCR and were confirmed by pyrosequencing. The overall estimated pool prevalence (EPP) of INKV in Norway was 0.04%. None of the analysed pools were positive for SINV. Overall IgG seroprevalence in reindeer was 62% positive for INKV by IIFA. Of the 60 reindeer sera- analysed by PRNT for INKV, 80% were confirmed positive, and there was no cross-reactivity with the closely related Tahyna virus (TAHV) and Snowshoe hare virus (SSHV). The occurrence and prevalence of INKV in BSI and the high seroprevalence against the virus among semi-domesticated reindeer in Norway indicate that further studies are required for monitoring this virus. SINV was not detected in the BSI in this study, however, human cases of SINV infection are yearly reported from other regions such as Rjukan in south-central Norway. It is therefore essential to monitor both viruses in the human population. Our findings are important to raise awareness regarding the geographical distribution of these mosquito-borne viruses in Northern Europe.


A rapid analytical method for measuring toluene in biological specimens.
A rapid and accurate method for the direct extraction and quantitation of toluene in blood and tissues has been developed. The technique involved extraction with methanol, selective adsorption onto Tenax, and desorption from the Tenax with heat and injection into a gas chromatograph. Measurement of standards indicated values were linear over a range of tissue concentrations of 1-1,734 microgram per gram of sample. The procedure described in this paper is a rapid, accurate method for measuring volatile hydrocarbon solvent in both blood and solid tissues of experimental animals. This technique should be applicable to basic research including animal studies, as well as to clinical cases involving abuse of or industrial exposure to solvents.


UDS activity in the rat liver of the human carcinogens benzidine and 4-aminobiphenyl, and the rodent carcinogens 3,3'-dichlorobenzidine and direct black 38.
The activity of benzidine and three structurally related carcinogens in an in vivo/in vitro rat liver assay for unscheduled DNA synthesis is described. The first three of these chemicals, benzidine, 4-aminobiphenyl (4AB) and Direct Black 38 have been reported as positive in this assay by other investigators, albeit the data reported for 4AB were limited. The fourth compound, 3,3'-dichlorobenzidine has not been studied in this assay before. Each compound gave a clear positive response under conditions of routine testing.


Adolescents with thyroid nodules: retrospective analysis of factors predicting malignancy.
Thyroid nodules are less common in children than in adults. However, pediatric thyroid nodules have a higher rate of malignancy compared to those in adults, and increased risk of metastasis and recurrence. In the present study, we analyzed the clinical features as well as laboratory and thyroid ultrasound (US) findings of children and adolescents with thyroid nodules to identify predictive factors of thyroid cancer. We retrospectively analyzed 275 patients with thyroid nodules under 18 years of age who visited Severance Children's Hospital between January 2005 and May 2017. Among them, 141 patients who underwent ultrasonography-guided fine needle aspiration biopsy (FNAB), and four patients without FNAB who underwent surgical resection, were included in this study. The remaining 125 patients without FNAB and five patients with follow-up loss after FNAB were excluded. Clinical, laboratory, and US data were evaluated in 145 patients to establish the potential predictive factors of thyroid cancer. Thyroid malignancies were observed in 101 patients. Grade 2 goiters were seen more often in benign nodule group. Hypoechoic nodules, nodules with microcalcifications, abnormal lymph nodes, and irregular margins were findings significantly associated with thyroid cancer. The findings of hypoechoic nodule, nodule with microcalcifications, and abnormal lymph nodes showed statistical significance in predicting thyroid cancer.Conclusion: Hypoechoic nodules, nodules with microcalcifications, and abnormal lymph nodes are predictive factors for thyroid cancer in children. Therefore, further diagnostic evaluations, including FNAB, should be considered in patients with such findings.What is Known:• Thyroid nodules are less common in children than in adults, but pediatric thyroid nodules have a higher rate of malignancy, and also have increased risk of metastasis and recurrence.• Research on ways to predict thyroid cancer have mostly been accomplished in adult patients, and the application of risk stratification system has not been fully satisfactory in children, which requires further studies in pediatric thyroid nodules.What is New:• Hypoechoic nodules, nodules with microcalcifications, and abnormal lymph nodes are predictive factors for thyroid cancer in Korean children.


The effectiveness of therapeutic patient education on adherence to oral anti-cancer medicines in adult cancer patients in ambulatory care settings: a systematic review.
Adherence to oral cancer medicines is a challenge for adult patients with cancer. Education specifically tailored for an individual patient with cancer may improve adherence. Therapeutic patient education when utilized effectively may maximize health outcomes and positively affect the quality of life of adult patients with cancer. Currently, there are no published systematic reviews specific to the effectiveness of therapeutic patient education on improvement of oral anti-cancer medicines adherence in patients with cancer. To synthesize the best available evidence on the effectiveness of therapeutic patient education on adherence to oral anti-cancer medicines in adult cancer patients 18 years and older in an ambulatory care setting. Types of participants: This review considered studies involving adults of any ethnicity, race or gender, aged 18 years or older who were diagnosed with any form of cancer, receiving oral anti-cancer medicines in an ambulatory care setting. Types of intervention(s): This review considered studies on the use of therapeutic patient education as the additional intervention to routine patient education for promoting oral anti-cancer medicine adherence in adult patients with cancer in an ambulatory care setting. Routine patient education was considered as a comparator. Types of outcomes: The outcome considered was adherence to prescribed oral anti-cancer medicines. Types of studies: This review considered experimental and observational studies. The literature search included published and unpublished studies in the English Language from 1953 through August 2014. A search of PubMed, CINAHL, Excerpta Medica Database, Academic Search Premier, Cochrane Library, PsycINFO, and Health Source: Nursing/Academic Edition was conducted using identified keywords and indexed terms across all included databases. A search for grey literature and electronic hand searching of relevant journals was also performed. Two reviewers independently evaluated the included studies for methodological quality utilizing standardized critical appraisal instruments from the Joanna Briggs Institute. Standardized data extraction tools were used by two reviewers independently as per the Joanna Briggs Institute for data extraction. Due to clinical and methodological heterogeneity between the included studies, statistical meta-analysis was not feasible. The results are presented in a narrative form. Two studies were included in this review, one randomized controlled trial and one cohort study. Both studies had small sample sizes and were moderate and low quality. The clinical significance of therapeutic patient education interventions and the relationship between behavior changes and health outcome changes remain unclear. The randomized clinical trial found a benefit in medication adherence rates in the tailored education intervention group compared to the standard education group at two and four months. Adherence rates measured by self-report (91.3% and 95.1%) and pharmacy refill rates (80% and 73.7%) were superior for the intervention group; however pharmacy refill rates were lower than self-reports of adherence. Tailored educational interventions were only beneficial on pharmacy refill rates (p=.0048) for promoting adherence at the two-month time interval. The cohort study found the intensified pharmaceutical educational intervention group demonstrated enhanced overall medication adherence then the standard education group (97.9% vs. 90.5%, p=0.069). The intervention group also showed a higher mean daily adherence to medication (96. 8% vs. 87.2%, p=0.029). The relative risk of the intervention group deviating from the medication intake interval of 12 hours was 0.51(95%CI, 0.46-0.56) compared to the control group (p<0.05, Chi-square test).The two studies showed no statistically significant differences, only modest to low evidence that therapeutic educational interventions support the clinical outcome of oral anti-cancer medicine adherence. There is a paucity of research evidence on the effectiveness of therapeutic patient educational interventions for improving patient adherence to oral cancer medicines. The effect of therapeutic patient educational interventions on oral anti-cancer medicine adherence has yet to be determined. Therapeutic patient educational interventions remain questionable, differing in format and educational strategies. A specific standardized methodology and evaluation approach to therapeutic patient education may reduce symptomatology, prevent side effects, maximize health outcomes and positively affect the quality of life and survival of adult patients with cancer. There is limited evidence that therapeutic patient educational interventions improve oral anti-cancer medicine adherence in adult patients with cancer in ambulatory care settings. A growing number of patients with cancer are being prescribed oral anti-cancer medicines; a better understanding of how therapeutic patient education strategies are effectively implemented may promote patient self-motivation and oral anti-cancer medicine adherence. This review recommends the development of a specific standardized methodology and evaluation approach to therapeutic patient education that may empower patients to increase their adherence to self-managed medication and achieve positive health outcomes Clinical trials with larger sample sizes, standardization of content, comparing specific adherence education or tailored education interventions are needed.


Behavioral and electrophysiological aspects of nitrous oxide dependence.
We examined the effect of 70% nitrous oxide (N2O) on locomotion and visual-evoked potentials (VEP) in rats. The animals exposed to N2O showed an initial decrease of locomotion, followed by development of tolerance and unaltered motor activity during N2O withdrawal. Similarly, an initial decrease of VEP amplitudes was followed by tolerance to N2O. In addition, some amplitudes (N2-P3, P3-N3, and N3-P4) exceeded the control values, indicating an increase of neuronal excitability of the visual system during a long lasting exposure to N2O. The increase of VEP amplitudes was further potentiated by cessation of this gas. The VEP latencies after initial increase, returned to normal and remained unaltered during N2O withdrawal suggesting that the speed of neurotransmission is not essentially changed during chronic exposure to N2O. However, a significant increase of neuronal excitability during chronic N2O exposure, which further increased by cessation of N2O, could be of clinical importance. Therefore, monitoring of VEP, particularly the amplitude values, may significantly improve a detection of altered neuronal excitability during anaesthesia and drug withdrawal.


Mycobacterium abscessus skin and soft tissue infection following autologous fat grafting in Kurdistan treated with an antibiotic combination including Imipenem-Relebactam and Rifabutin.
Medical tourism is becoming increasingly popular. The most popularly sought operations are cosmetic procedures. With the increase in cosmetic tourism, it is unsurprising that there has also been a rise in skin and soft tissue infections caused by nontuberculous mycobacteria (NTM); in particular by the rapidly growing mycobacteria species. Here we provide a case of a 35 year-old woman who presented after autologous fat grafting with multiple painful, violaceous, and purulent nodules on her arms, legs, and breasts. Infection was found to be due to Mycobacterium abscessus. She was successfully treated with azithromycin, clofazimine, rifabutin, amikacin, imipenem-cilastatin-relebactam (Recarbrio™) and imipenem-cilastatin. This is the first described case of a M. abscessus infection successfully treated using this combination.


Fully automated LC method for the determination of sotalol in human plasma using restricted access material with cation exchange properties for sample clean-up.
A simple and rapid fully automated bio-analytical method for the liquid chromatographic (LC) determination of sotalol in human plasma has been described. The method is based on the use of a new kind of porous silica restricted access material (RAM) with cation exchange properties for sample clean-up. 100 microl of plasma samples were directly injected into the precolumn coupled on-line to a reversed-phase column (RP-Select B) by means of column switching system. The plasma matrix was washed out for 10 min using a washing liquid composed of 2 mM lithium perchlorate and methanol (97:3; v/v). By rotation of the switching valve, the analytes were then eluted in back-flush mode for 2 min and transferred to the analytical column by the LC mobile phase constituted of a mixture of methanol and 50 mM potassium phosphate buffer (pH 7.0) containing 1 mM 1-octanesulphonic acid sodium salt (20:80; v/v). The flow-rate was 1.0 ml/min and sotalol was detected using fluorescence detection at 235 and 300 nm as excitation and emission wavelengths, respectively. The method was then validated using a new approach based on accuracy profile over a concentration range from 5 to 500 ng/ml. The limit of quantitation (LOQ) was 5 ng/ml and the total analysis time was 19 min.


Reply to Li et al.: Comment on "Effects of Carbohydrate Mouth Rinse on Cycling Time Trial Performance: A Systematic Review and Meta-Analysis".


Why would we expect the mind to work that way? The fitness costs to inaccurate beliefs.
An adaptationist analysis of beliefs yields the prediction that we ought to expect accuracy in the cognitive systems which generate them - stereotypes or otherwise - for the most part. There are, however, some limited situations in which some inaccuracy in beliefs advertised to others might be adaptive.


Endotoxemia in obstructive jaundice. Observations on cause and clinical significance.
Perioperative endotoxemia was detected in 24 of 40 patients who underwent operation for obstructive jaundice (bilirubin level greater than 5.8 mg/dl). Endotoxemia was associated with an increased admission serum bilirubin level (p less than 0.05) and white blood cell count (p less than 0.05) and a decreased hematocrit value (p less than 0.05), but there was no significant association with other established preoperative risk factors. Patients with preoperative endotoxemia had a decreased immunoglobulin M anti-J5 endotoxin titer (p less than 0.05) and a decreased serum bile acid concentration (p less than 0.05). Preoperative endotoxemia was associated with reduced creatinine clearance before and after operation (p less than 0.05). There was no association between endotoxemia and clinical sepsis, gram-negative infection, or small-bowel colonization. Patients who died had increased preoperative serum fibrin degradation products (p less than 0.05).


The effect of bovine serum albumin on the synthesis of prostaglandin and incorporation of [3H]acetate into platelet-activating factor.
The binding of fatty acids by bovine serum albumin (BSA) is well documented. However, the interaction between the synthesis of prostaglandins (PGs) and the trapping of arachidonate released from cellular lipid stores is not as well understood. In this communication, we relate the trapping of fatty acids to the synthesis of PGs and the incorporation of [3H]acetate into platelet-activating factor (PAF). Our results show that, as determined by radioimmunoassay, BSA inhibits bradykinin (BK) (5 ng/ml) and ionophore A23187 (10 microM)-stimulated synthesis of PGs in human embryo lung fibroblasts (IMR-90) in a concentration-dependent manner. Experiments using prelabel with [3H]arachidonate followed by extraction and thin-layer chromatography show that, in the presence of 2 mg/ml BSA, IMR-90 release essentially only fatty acid following stimulation with bradykinin. Little if any prostaglandin and no endoperoxide are detected. In the same experiment, in absence of BSA, about 70% of the released label is detected as prostaglandin. alpha-Cyclodextrin, another trapper of fatty acid, inhibits PG synthesis in much the same way. BSA and alpha-cyclodextrin also inhibit prostacyclin synthesis in endothelial cells derived from the calf pulmonary artery. However, the inhibition of PG synthesis in these cells is not as complete as that in the IMR-90. In contrast to the effect of the trappers on PG synthesis, BSA and alpha-cyclodextrin are observed to potentiate BK- and ionophore-stimulated incorporation of [3H]acetate into PAF in the endothelial cells. The labeled PAF is not released from the cells in either the presence or absence of the trappers, leading us to conclude that BSA causes an increase in acetate-labeled cellular PAF by trapping released fatty acid.


Endocarditis in an infant causing "tricuspid atresia".
A 3-month-old male infant died of tricuspid valve nonbacterial thrombotic endocarditis complicating disseminated intravascular coagulation. The vegetations were so extensive as to cause tricuspid atresia and led to congestive right ventricular failure terminating in death. The diagnosis was made only at post mortem.


Preclinical detection of infectivity and disease-specific PrP in blood throughout the incubation period of prion disease.
Variant Creutzfeldt-Jakob disease (vCJD) is a fatal neurodegenerative disorder characterised by accumulation of pathological isoforms of the prion protein, PrP. Although cases of clinical vCJD are rare, there is evidence there may be tens of thousands of infectious carriers in the United Kingdom alone. This raises concern about the potential for perpetuation of infection via medical procedures, in particular transfusion of contaminated blood products. Accurate biochemical detection of prion infection is crucial to mitigate risk and we have previously reported a blood assay for vCJD. This assay is sensitive for abnormal PrP conformers at the earliest stages of preclinical prion disease in mice and precedes the maximum infectious titre in blood. Not only does this support the possibility of screening asymptomatic individuals, it will also facilitate the elucidation of the complex relationship that exists between the ensemble of abnormal PrP conformers present in blood and the relationship to infectivity.


Immunohistochemical localization of pulmonary surfactant apoproteins in various lung tumors. Special reference to nonmucus producing lung adenocarcinomas.
Eighty-nine primary lung carcinomas and 23 metastatic lung tumors were immunohistochemically studied for the expression of pulmonary surfactant apoproteins, by using monoclonal (PE-10) and polyclonal antibodies. Surfactant apoprotein was demonstrated in the cytoplasm and/or nuclear inclusion bodies of only primary lung adenocarcinomas (36 of 75 cases), not in any other histologic type of primary lung carcinoma or in metastatic lung tumors. In primary lung adenocarcinoma, although typical type II pneumocyte type adenocarcinoma was not included in the current series, the majority of surfactant apoprotein-positive single cell type tumors were of the Clara cell type, with a single bronchial surface epithelial cell type, according to the light microscopic subclassification of adenocarcinoma cells. The Clara cell type adenocarcinomas could at times be distinguished only with difficulty from adenocarcinoma of type II pneumocyte type. Normal and hyperplastic type II pneumocytes were of course positive for surfactant apoprotein in the cytoplasm. However, none of the positive cells could definitely be identified as Clara cells in non-neoplastic lungs. The findings obtained in this study indicate that surfactant apoprotein is a good marker to distinguish adenocarcinoma of the lung from other histologic types of lung cancer and from neoplasms metastatic to the lung, and that type II pneumocytes and Clara cells, non-neoplastic and neoplastic, are morphologically and functionally closely related and might belong to the same cell lineage.


Novel Imaging Biomarker Prediction of Parenchymal Hemorrhage after Mechanical Thrombectomy in Patients with Large Ischemic Core.
Recently studies have shown that select acute ischemic stroke (AIS) patients with large ischemic core could be deemed as reasonable candidates to receive mechanical thrombectomy (MT) with low risk of developing parenchymal hemorrhage (PH) or symptomatic intracerebral hemorrhage (sICH); however, the selection criterion remains lacking. Our study aims to investigate the relationship between a novel imaging biomarker of largest core mass volume (LCMV) and development of PH in stroke patients with large ischemic core who have undergone MT. A total of 26 AIS patients with large ischemic core (defined as ischemic core volume ≧ 50 ml) were enrolled in the study. Volume of ischemic core and the LCMV measured with Mistar software were measured in all patients. Fourteen patients with AIS developed PH while 12 patients showed no signs of PH based on CT imaging obtained between 24 h and 3 day after MT. We compared the volume of ischemic core and LCMV between two groups. Volume of ischemic core showed no significant difference between the PH and no PH group [105.5 (62.4-131.5) vs 75.0 (56.3-102.2), p = 0.105], whereas LCMV was significantly higher in the PH (14.80 ± 5.23) vs. no PH group (8.40 ± 2.61, p = 0.001). ROC analysis revealed that LCMV was positively correlated with PH (area under the curve = 0.905). The optimal LCMV associated with PH was ≧ 9.67 ml. LCMV is an effective and easy-to-use imaging biomarker to predict PH after MT in AIS patients with large ischemic core.


Relations of QTc prolongation on the electrocardiogram to torsades de pointes: definitions and mechanisms.
Antiarrhythmic drug-induced ventricular tachyarrhythmias have traditionally been identified on the basis of prolongation of the QT interval and the appearance of undulating peaks of sequential QRS complexes and T waves that give the tachycardia a "twisting" aspect (so-called torsades de pointes). It is now understood, however, that a precise lengthening of the QT interval is not a necessary or sufficient criterion for the development of torsades de pointes associated with drug therapy. Indeed, not all agents that have been linked with torsades de pointes cause significant lengthening of the QT interval. Moreover, sufficiently accurate determination of QT interval duration to judge a prolongation is confounded by a number of difficulties, including considerable intraindividual variability. It is possible that the development of abnormal giant U waves may be involved in the genesis of these tachyarrhythmias. Such U waves are believed to represent the summation of early afterdepolarizations occurring throughout the myocardium. The prepause ventricular rate determines the amplitude of the U wave, and larger U waves give rise to longer and faster runs of ventricular tachycardia. These arrhythmias tend to be self-perpetuating in a bigeminal feedback pattern. At present, our knowledge base about the relation of the QT interval and torsades de pointes is grossly incomplete. More basic and clinical data are required before hard clinical judgments can be made with any precision.


Evaluation of liquid-liquid extraction process for separating acrylic acid produced from renewable sugars.
In this article, the separation and the purification of the acrylic acid produced from renewable sugars were studied using the liquid-liquid extraction process. Nonrandom two-liquids and universal quasi-chemical models and the prediction method universal quasi-chemical functional activity coefficients were used for generating liquid-liquid equilibrium diagrams for systems made up of acrylic acid, water, and solvents (diisopropyl ether, isopropyl acetate, 2-ethyl hexanol, and methyl isobutyl ketone) and the results were compared with available liquid-liquid equilibrium experimental data. Aspen Plus (Aspen Technology, Inc., version 2004.1) software was used for equilibrium and process calculations. High concentration of acrylic acid was obtained in this article using diisopropyl ether as solvent.


Identification of elongating beta-1,4-galactosyltransferase activity in mung bean (Vigna radiata) hypocotyls using 2-aminobenzaminated 1,4-linked beta- D-galactooligosaccharides as acceptor substrates.
Galactosyltransferase (GalT) activity that results in the transfer of galactose (Gal) from UDP-Gal to exogenous (1-->4)-beta-galactooligosaccharides labeled with 2-aminobenzamide (2AB) at their reducing ends was identified in a particulate preparation obtained from 2-day-old mung bean (Vigna radiata L. Wilezek) hypocotyls. The enzymes responsible were shown, by high-performance anion-exchange chromatography and normal-phase liquid chromatography-electrospray ionization mass spectrometry, to transfer up to eight Gals to the non-reducing end of 2AB-labeled galactooligosaccharide. Using 1H nuclear magnetic resonance spectroscopy, and beta-galactosidase and endo-beta-(1-->4)-galactanase treatments of the enzymatically formed 2AB-labeled galactooligosaccharides, the newly incorporated Gal residues were shown to be beta-(1-->4) linked. Time-course studies indicated that at least two different types of GalT isoform are involved in the elongation of the acceptor substrates. 2AB-labeled galactoheptaose was the most effective acceptor substrate analyzed, although galactooligosaccharides with a degree of polymerization between 4 and 6 were also acceptor substrates. 2AB-labeled penta- and heptasaccharides (RG5 and RG7) generated from rhamnogalacturonan I (RG-I) were not acceptor substrates, suggesting that the GalTs were not capable of adding Gal residues directly to the RG-I backbone. Maximum GalT activity was obtained at pH 6.5 and 20 degrees C in the presence of 25 mM Mn2+ and 0.75% (w/v) Triton X-100. The enzyme had an apparent Km of 20 microM for 2AB-labeled galactoheptaose and 32 microM for UDP-Gal. The characteristics of the enzyme in mung bean microsomal membranes and the usefulness of fluorogenic 2AB-labeled galactooligosaccharides for the assay of GalT are discussed.


Errorless (re)learning of everyday activities in patients with Korsakoff's syndrome: A feasibility study.
Errorless learning has proven to be an effective method for (re)learning tasks in several patient groups with amnesia. However, so far only a handful of studies have examined the effects of errorless learning in patients with Korsakoff's syndrome. The aims of this feasibility study were to (a) examine the effects of errorless learning training on (re)learning tasks in a patient with Korsakoff's syndrome, (b) examine the effects of the nature of the training on the execution of the tasks, and (c) examine characteristics that may mediate learning outcome. Professional caregivers, who were trained in errorless learning principles, taught 51 patients with Korsakoff's syndrome two everyday tasks. Significant improvements in the performance were found after an errorless intervention for different types of trained tasks (activities of daily living, chores, mobility, housekeeping). Moreover, the results of this study suggest that all patients, despite of age, educational level, or level of cognitive functioning, may benefit from errorless learning. The results showed that, despite severe amnesia, patients with Korsakoff's syndrome have the potential to (re)learn everyday skills. Errorless learning might be beneficial for memory rehabilitation in patients with Korsakoff's syndrome in clinical practice. The results of this study are clinically relevant, as successfully learning tasks using errorless learning principles might improve autonomy and independence in the daily lives of patients with Korsakoff's syndrome.


Effect of aflatoxins on testicular steroidogenesis and amelioration by vitamin E.
The potential of aflatoxin to affect testicular steroidogenesis and its amelioration by vitamin E was assessed in the present investigation. Oral administration of aflatoxin (25 and 50 microg/animal/day) for 45 days to adult mice caused, as compared with control, a dose-dependent significant rise in cholesterol content. However, the activities of 3beta- and 17beta-hydroxysteroid dehydrogenases and serum testosterone levels were significantly reduced in aflatoxin-treated mice as compared with the controls. Pretreatment with vitamin E (2 mg/animal/day, orally) significantly ameliorated aflatoxin-induced changes as compared with aflatoxin treatment alone. The present investigation clearly indicates that vitamin E ameliorates aflatoxin-induced changes in steroidogenesis.


Parotid gland, an exceptional localization of sebaceous carcinoma: case report.
Sebaceous carcinoma (SC) is a rare malignancy, occurring predominantly in eyelids. Till date, only 25 cases of sebaceous carcinoma (SC) of the parotid gland have been reported in world literature. A 33 year-old male presented with left sided laterocervical mass. Clinical examination showed enlargement of the left parotid gland, with cervical lymphadenopathy. No skin lesions were found. A resection of the gland was performed. Pathological findings were consistent with primary sebaceous carcinoma of the parotid gland. Sebaceous carcinoma of the parotid gland is extremely uncommon. Clinical and radiological features are not specific. The aim of this report, is to describe histopathological, and immunohistochemical findings of this rare entity, and discuss differential diagnosis.


A comprehensive study on surveillance outcomes of a male population followed at a hereditary breast cancer high-risk consultation at a Portuguese tertiary hospital.
Men born with pathogenic/likely pathogenic variants in genes associated with the Hereditary Breast and Ovarian Cancer Syndrome have a higher risk to develop breast cancer and other cancers (such as prostate cancer) and should undergo adequate surveillance protocols in highly specialized Centers. A retrospective study was conducted to assess these genetic variants' epidemiological and phenotypical manifestations in male carriers, as well as the efficacy of the surveillance protocol and compliance toward it through a survey. During follow-up, a genetic panel for testing was implemented, the starting age for surveillance was delayed, and the six-month screening interval was extended to annual. A total of 104 men from a tertiary hospital's High-Risk Consultation were included, 102 with positive genetic testing for BRCA1 (n = 31), BRCA2 (n = 55), both BRCA2 and another gene (n = 5), CDH1 (n = 2), CHEK2 (n = 4), NF1 (n = 1), RAD51C (n = 4), and an additional two men with no actionable genetic variant identified. The follow-up period ranged from 1 to 13 years, and only one man developed cancer. Survey responses from 48 men in active surveillance showed that more than half recognizes their carrier status and consequent surveillance impact on their life, including the risk of transmission to offspring, fear of future cancer, meaningful distress, and feeling of injustice. Biannual surveillance was not actively detecting more cancer disease cases, confirming the adequacy of the currently implemented protocol CONCLUSION: With support of Genetics to fulfill the current gaps in high-risk management, the proposed redefinition of surveillance protocol would adapt it to the population needs and concerns.


Effect of folic acid and vitamin B12 deficiencies on 5-hydroxyindoleacetic acid in human cerebrospinal fluid.
Indoles were measured in cerebrospinal fluid (CSF) from control patients, from patients suffering from folate deficiency, and from patients with vitamin B12 deficiency. The folate-deficient patients were classified according to whether they exhibited a neuropsychiatric syndrome, consisting of organic mental changes, polyneuropathy, and depression, which responded to folate administration. CSF 5-hydroxyindoleacetic acid was low in the vitamin B12-deficient patients and in those folate-deficient patients whose symptoms were not related to folate deficiency. CSF 5-hydroxyindoleacetic acid returned to normal with folate treatment in the patients exhibiting folate-responsive neuropsychiatric signs. The data indicate a close association between folate-responsive neuropsychiatric symptoms and changes in 5-hydroxytryptamine metabolism in the central nervous system.


Isolation of toxic metal-tolerant bacteria from soil and examination of their bioaugmentation potentiality by pot studies in cadmium- and lead-contaminated soil.
Heavy metals, also regarded as toxic metals, are the important environmental pollutants that affect all forms of life. Accumulation of toxic metals in plants results in various biochemical, physiological and structural disturbances, leading to inhibited growth and sometimes plant death. Toxic metal contamination disturbs the soil ecology as well as the agricultural productivity. Several indigenous microbes can withstand the effect of toxic metal and play a vital role in the revival of tarnished soil. In the present study, soil samples were collected from contaminated crop field of Cachar district of Assam, India. Segregation, enumeration and identification of bacteria from soil samples were performed. Among all the tested isolates, very few were able to withstand a high concentration of Cd and Pb in nutrient agar plates. Toxic metal-tolerant bacteria were identified as Pseudomonas aeruginosa and Bacillus cereus. The isolates having a higher tolerance for Cd and Pb were taken into consideration for pot studies. P. aeruginosa strain SN4 and strain SN5 showed significant results at Cd- and Pb-contaminated soil, evidenced by the healthy growth of Oryza sativa seedlings. However, B. cereus strain SN6 showed high tolerance towards Cd and Pb, but pot experimental studies showed adverse effects on seedling germination and shoot growth of O. sativa. P. aeruginosa strains were significantly able to reduce the negative impact of Cd and Pb in the soil, thus finding an alternative in removal, recovery and remediation of toxic metal-contaminated crop field.


Understanding the Elevated Lethality of COVID-19 in Liver Transplant Recipients: Does Immunosuppression Management Matter? Results from a Brazilian Multicentric Historical Cohort.
Infections by SARS-CoV-2 in liver transplant recipients (LT) patients are of particular concern, notably due to perceived added risks related to immunosuppression and comorbidity burden. Current literature on this topic often relies on small, non-standardized, and geographically limited studies. This manuscript describes COVID-19 presentations and causes for elevated mortality in a large cohort of LT recipients. This study was designed as a multicentric historical cohort, including LT recipient patients with COVID-19 in 25 study centers, with the primary endpoint being COVID-related death. We also collected demographic, clinical, and laboratory data regarding presentation and disease progression. Two hundred and thirty-four cases were included. The study population was predominantly male and White and had a median age of 60 years. The median time from transplantation was 2.6 years (IQR 1-6). Most patients had at least one comorbidity (189, 80.8%). Patient age (P = .04), dyspnea (P < .001), intensive care unit admission (P < .001), and mechanical ventilation (P < .001) were associated with increased mortality. Modifications of immunosuppressive therapy (P < .001), specifically the suspension of tacrolimus, maintained significance in multivariable analysis. Attention to risk factors and the individualization of patient care, especially regarding immunosuppression management, is crucial for delivering more precise interventions to these individuals.


Homosexuality in families of boys with early effeminate behavior: an epidemiological study.
In the course of a long-term study of 55 boys with early effeminate (cross-gender) behavior an effort was also made to ascertain the presence of sexual deviance in their parents, siblings, uncles, and aunts. For most of these groups of relatives, only one to three members in each group were found to be homosexual, equaling 4% male and 1% female for the total test population. Compared to similar studies, the results were not too different except in the case of the siblings of one study where the incidence was much higher. Some evidence is considered for the speculation of a nongenetic, congenital cause of homosexuality.


Deletion of the Notch ligand Jagged1 during cochlear maturation leads to inner hair cell defects and hearing loss.
The mammalian cochlea is an exceptionally well-organized epithelium composed of hair cells, supporting cells, and innervating neurons. Loss or defects in any of these cell types, particularly the specialized sensory hair cells, leads to deafness. The Notch pathway is known to play a critical role in the decision to become either a hair cell or a supporting cell during embryogenesis; however, little is known about how Notch functions later during cochlear maturation. Uniquely amongst Notch ligands, Jagged1 (JAG1) is localized to supporting cells during cell fate acquisition and continues to be expressed into adulthood. Here, we demonstrate that JAG1 in maturing cochlear supporting cells is essential for normal cochlear function. Specifically, we show that deletion of JAG1 during cochlear maturation disrupts the inner hair cell pathway and leads to a type of deafness clinically similar to auditory neuropathy. Common pathologies associated with disruptions in inner hair cell function, including loss of hair cells, synapses, or auditory neurons, were not observed in JAG1 mutant cochleae. Instead, RNA-seq analysis of JAG1-deficient cochleae identified dysregulation of the Rho GTPase pathway, known to be involved in stereocilia development and maintenance. Interestingly, the overexpression of one of the altered genes, Diaph3, is responsible for autosomal dominant auditory neuropathy-1 (AUNA1) in humans and mice, and is associated with defects in the inner hair cell stereocilia. Strikingly, ultrastructural analyses of JAG1-deleted cochleae revealed stereocilia defects in inner hair cells, including fused and elongated bundles, that were similar to those stereocilia defects reported in AUNA1 mice. Taken together, these data indicate a novel role for Notch signaling in normal hearing development through maintaining stereocilia integrity of the inner hair cells during cochlear maturation.


Cavum septum pellucidum cyst in children: a case-based update.
Cavum septum pellucidum (CSP) cysts are rare lesions which are frequently asymptomatic. Some clinical findings may be associated with CSP cysts, such as headache and other symptoms of increased intracranial pressure, neurological deficit, and mental status changes. There is still controversy in the management of symptomatic cases, especially in children. The main difficulty is to establish a correlation between symptoms and the cyst. When indicated, the treatment is essentially surgical, and the ideal operative technique is also a matter of debate. We present a case of a 14-year-old boy with a symptomatic CSP cyst who was successfully treated by neuronavigation-assisted neuroendoscopy with a bilateral fenestration. A literature review is provided with regard to clinical presentation, treatment, and outcome in children. The treatment is considered whenever there is an association of a CSP cyst on imaging studies and symptoms attributable to the obstruction of the cerebrospinal fluid flow or direct compression of surrounding structures by the cyst. Endoscopic fenestration is a less invasive and highly effective technique, and is currently the treatment of choice for such lesions in children.


One-year stability for a glucose/oxygen biofuel cell combined with pH reactivation of the laccase/carbon nanotube biocathode.
This study reports a mixed operational/storage stability of a MWCNT-based glucose biofuel cell (GBFC) over one year. The latter was examined by performing a one hour discharge every day during one month followed by several discharges over a period of 11 months. Under continuous discharge in physiological conditions (5 mM glucose, 37°, pH7), the GBFC exhibits a 25% power decrease after 1 h of operation. This decrease is mainly due to the deactivation of laccase biocathodes at neutral pH. Nevertheless, the biocathodes can be reversibly reactivated via storage in phosphate buffer (pH 5). Under these conditions, the GBFC finally exhibits 22% of its initial maximum power density after one year at intermittent reactivation/discharge cycles. Although both GBFC electrodes can exhibit one year stability, short-term experiments show that biocathodes are limited by hydroxide inhibition while long-term experiments indicate that bioanodes are likely limited by the stability of the GOx itself. While most of the GBFCs in the literature present stability in the range of several weeks, these results demonstrate the viability of a GBFC for industrial applications in a long period of time.


[Incidence of biological tests requested outside of written medical prescriptions in digestive surgical intensive care unit].
Realization of biological tests in intensive care unit requires a written medical prescription. Requests of biological tests outside written medical prescription are sometimes observed. The aim of the survey was to evaluate their incidence and the reasons of these practices. The study was realized on a 14 days-period in a 8 beds intensive care unit of digestive surgery, in real situation and anyone was informed of the study. Nineteen patients were enrolled during the period of the study. A request of biological tests outside written medical prescription was found in 78% of requests of tests (89/114). The incidence of requests of biological tests outside written medical prescription was 27%. Several reasons could explain these practices. This study confirms that there is a high frequency of requests of biological tests outside written medical prescription and that several reasons could explain these practices in intensive care unit.


Surgical training in the Netherlands.
Surgical training in the Netherlands has traditionally been characterized by learning on the job under the classic master-trainee doctrine. Over the past decades, it has become regionally organized with intensive structural training courses, and a peer-based quality control system. Recently, the nationwide programme has been modernized further and now involves a systematic, competency-based education with structural training courses, formalized assessment and room for reflection by residents under the supervision of surgical teaching groups. To this end, a uniform web-based digital portfolio is being introduced to facilitate monitoring of the individual resident's progress. Though requiring inspirational leadership, commitment, and determination, this modernization has sparked enthusiasm among trainees and teachers.


Two patterns of clinical recovery in Guillain-Barré syndrome with IgG anti-GM1 antibody.
To investigate the prognostic value of anti-GM1 antibody. Whether anti-GM1 antibody is a marker of poor prognosis due to axonal degeneration in Guillain-Barré syndrome (GBS) is a matter of controversy. The clinical recovery of 41 consecutive GBS patients was analyzed. The Hughes functional grading scores were similar at the peak, and 1, 3, and 6 months after onset for the groups of patients with (n=19) and without (n=22) immunoglobulin (Ig) G anti-GM1 antibodies. However, the anti-GM1-positive group included significantly higher proportions of patients with poor recovery (inability to walk independently at 6 months, 5 of 19 versus 0 of 22; p=0.01) and those with a markedly rapid recovery (improvement by two or more Hughes grades within a month, 9 of 19 versus 4 of 22; p=0.05). The positivity of IgG anti-GM1 antibody correlated well with the electrodiagnosis of the acute motor axonal neuropathy pattern but was not always associated with poor prognosis. Anti-GM1-positive patients showed two different patterns of clinical recovery-their conditions improved slower or faster than those of the anti-GM1-negative patients, most of whom had acute inflammatory demyelinating polyneuropathy. Anti-GM1 antibody is not always a marker of poor prognosis and, besides axonal degeneration, early reversible effects other than demyelination could be part of the pathophysiology of Guillain-Barré syndrome with IgG anti-GM1 antibody.


Management and Follow-Up of Biventricular Thrombi.
A thrombus is the most common intracardiac lesion. Isolated thrombi usually occur in the setting of ventricular dysfunction, such as a dyskinetic or hypokinetic myocardial wall, following an acute myocardial infarction (MI) or in cardiomyopathies (CM). Concurrent biventricular thrombus formation is rare. There are no clear guidelines for the treatment of biventricular thrombus. In this report, we describe our experience of the successful treatment of a case of biventricular thrombus with warfarin and rivaroxaban.


Systemic lupus erythematosus and other autoimmune rheumatic diseases: challenges to treatment.
Increased understanding of the molecular mechanisms underlying the pathogenenesis of autoimmune rheumatic diseases has led to targeted biological treatments that modulate various aspects of the immune response. These new treatments, together with more judicious use of other immunosuppressive drugs, have resulted in marked improvements in morbidity and mortality. Although belimumab, an agent that inhibits B-cell survival, is the first drug to be approved by the US Food and Drug Administration for the treatment of systemic lupus erythematosus in 50 years, many other immunological targets are under investigation. We discuss the recent advances in the biological treatment of autoimmune rheumatic diseases, with a particular focus on systemic lupus erythematosus.


Cardiac abnormalities in a female patient with hypogonadotropic hypogonadism with anosmia.
Hypogonadotropic hypogonadism with anosmia was found in a 38 year old female. Cardiac abnormalities were manifested by a second degree heart block as well as a conduction delay below the AV node. Striking T wave inversions developed in the absence of any symptoms. These changes probably reflect a central nervous system defect.


Lack of evidence for integration of Trypanosoma cruzi minicircle DNA in South American human genomes.
Horizontal gene transfer involving kinetoplast DNA minicircles between Trypanosoma cruzi and its mammalian hosts has recently been proposed as a usual consequence of infection (Hecht et al., 2010). However, we have found no sequences longer than 29 bp perfectly matching minicircles of T. cruzi in the unassembled reads from Colombian and Peruvian human populations provided by the 1,000 Genome project (129 individuals in total, coverage from 1.4× to 36.3×, read length from 42 to 101 bp). The weak sequence matches that were identified are shared with a Finnish population used as a control from a non-endemic area.


Altered deoxyribonucleotide pools in T-lymphoblastoid cells expressing the multisubstrate nucleoside kinase of Drosophila melanogaster.
The multisubstrate nucleoside kinase of Drosophila melanogaster (Dm-dNK) can be expressed in human solid tumor cells and its unique enzymatic properties makes this enzyme a suicide gene candidate. In the present study, Dm-dNK was stably expressed in the CCRF-CEM and H9 T-lymphoblastoid cell lines. The expressed enzyme was localized to the cell nucleus and the enzyme retained its activity. The Dm-dNK overexpressing cells showed approximately 200-fold increased sensitivity to the cytostatic activity of several nucleoside analogs, such as the pyrimidine nucleoside analogs (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU) and 1-beta-d-arabinofuranosylthymine (araT), but not to the antiherpetic purine nucleoside analogs ganciclovir, acyclovir and penciclovir, which may allow this technology to be applied in donor T cells and/or rescue graft vs. host disease to permit modulation of alloreactivity after transplantation. The most pronounced effect on the steady-state dNTP levels was a two- to 10-fold increased dTTP pool in Dm-dNK expressing cells that were grown in the presence of 1 microm of each natural deoxyribonucleoside. Although the Dm-dNK expressing cells demonstrated dNTP pool imbalances, no mitochondrial DNA deletions or altered mitochondrial DNA levels were detected in the H9 Dm-dNK expressing cells.


Blood-brain barrier integrity in a mouse model of Alzheimer's disease with or without acute 3D6 immunotherapy.
The blood-brain barrier (BBB) is suggested to be compromised in Alzheimer's disease (AD). The concomitant presence of vascular amyloid beta (Aβ) pathology, so called cerebral amyloid angiopathy (CAA), also predisposes impairment of vessel integrity. Additionally, immunotherapy against Aβ may lead to further damage of the BBB. To what extent this affects the BBB passage of molecules is debated. The current study aimed to investigate BBB integrity to large molecules in transgenic mice displaying abundant Aβ pathology and age matched wild type animals, with or without acute anti-Aβ antibody treatment. Animals were administered a single i.v. injection of PBS or 3D6 (10 mg/kg), i.e. the murine version of the clinically investigated Aβ antibody bapineuzumab, supplemented with [125I]3D6. Three days post injections, a 4 kDa FITC and a 150 kDa Antonia Red dextran were administered i.v. to all animals. After termination, fluorescent detection in brain and serum was used for the calculation of dextran brain-to-blood concentration ratios. Further characterization of antibody fate and the presence of CAA were investigated using radioactivity measurements and Congo red staining. BBB passage of large molecules was equally low in wild type and transgenic mice, suggesting an intact BBB despite Aβ pathology. Neither was the BBB integrity affected by acute 3D6 treatment. However, CAA was confirmed in the transgenes and local antibody accumulations were observed in the brain, indicating CAA-antibody interactions. The current study shows that independently of Aβ pathology or acute 3D6 treatment, the BBB is intact, without extensive permeability to large molecules, including the 3D6 antibody.


Simple and low-cost production of magnetite/graphene nanocomposites for heavy metal ions adsorption.
It is challenging to produce economical magnetic graphene-based adsorbents on an industrial scale for heavy metal ions removal. Here, magnetite/graphene nanocomposite embedded in activated carbon matrix (magnetite/G-AC) was synthesized via in situ catalytic graphitization of iron-impregnated biochar to obtain graphene encapsulated iron nanoparticles (GEINs) embedded in biochar (BC) matrix, and followed by steam activation of GEINs-BC. Steam activation aimed to upgrade biochar to activated carbon with oxygen functional groups, crack encapsulated graphene shell to graphene nanosheets, and obtain magnetic Fe3O4 by oxidation of iron, thereby improving the adsorption capacity of magnetite/G-AC-800 (153.2 mg/g) four times higher than that of GEINs-BC. The parameters on the adsorption capacity were investigated using Pb(II) ions as a typical pollutant as a function of solution pH (3-7), contact time (5-300 min), initial Pb(II) concentration (50-400 mg/L), and adsorbent dosage (0.05-0.25 g). The fitted pseudo-second-order kinetic model and Langmuir model indicated that the main adsorption mechanism was chemical adsorption over monolayer. This research developed a low-cost magnetic adsorbent with the advantage of simple large-scale production and excellent adsorption capacity per unit cost for remediating wastewater.


Activities related to environmental specimen banking in Japan.
Some experiments on the preservability of chemicals in environmental samples such as atmospheric particulate matters and mussel meat have been conducted by National Institute for Environmental Studies (NIES), Japan, as a preliminary study for future establishment of environmental specimen bank. NIES also has been operating a small experimental sample bank, storing several kinds of environmental samples. Closely cooperating with NIES, Environment Agency of Japan has been performing several types of nationwide environmental monitoring of chemical substances and some parts of the collected samples have been stored in the cold storage room for future use. A retrospective analysis of TBT and TPT in the fish using these stored samples showed an availability and usefulness of specimen bank for the long term monitoring of pollutants.


Synthesis of spirofluorenes of biological interest.
1'-Substituted spiro[fluorene-9,3'-pyrrolidine-2',5'-diones], 1',1''' - (1,4-piperazinediyldimethylene) bis[spiro[fluorene-9,3'-pyrrolidine-2',5'-dione]], and 1'-arylspiro[fluorene-9,3'-pyrrolidines] were synthesized from spiro[fluorene-9,3'-tetrahydrofuran-2',5'-dione]. The rat passive cutaneous anaphylaxis assay showed that one compound possessed slight antiallergic activity. Synthesis of 3-substituted 1-aryl-4-oxospiro[azetidine-2,9'-fluorenes] and 1,1''-p-phenylenebis[4-oxospiro[azetidine-2,9'-fluorenes]] was achieved via the reaction of appropriate N-fluorenylideneanilines with tert-butylcyanoketene and cyclopentamethyleneketene, respectively.


The non-competitive acetylcholinesterase inhibitor APS12-2 is a potent antagonist of skeletal muscle nicotinic acetylcholine receptors.
APS12-2, a non-competitive acetylcholinesterase inhibitor, is one of the synthetic analogs of polymeric alkylpyridinium salts (poly-APS) isolated from the marine sponge Reniera sarai. In the present work the effects of APS12-2 were studied on isolated mouse phrenic nerve-hemidiaphragm muscle preparations, using twitch tension measurements and electrophysiological recordings. APS12-2 in a concentration-dependent manner blocked nerve-evoked isometric muscle contraction (IC(50)=0.74 μM), without affecting directly-elicited twitch tension up to 2.72 μM. The compound (0.007-3.40 μM) decreased the amplitude of miniature endplate potentials until a complete block by concentrations higher than 0.68 μM, without affecting their frequency. Full size endplate potentials, recorded after blocking voltage-gated muscle sodium channels, were inhibited by APS12-2 in a concentration-dependent manner (IC(50)=0.36 μM) without significant change in the resting membrane potential of the muscle fibers up to 3.40 μM. The compound also blocked acetylcholine-evoked inward currents in Xenopus oocytes in which Torpedo (α1(2)β1γδ) muscle-type nicotinic acetylcholine receptors (nAChRs) have been incorporated (IC(50)=0.0005 μM), indicating a higher affinity of the compound for Torpedo (α1(2)β1γδ) than for the mouse (α1(2)β1γε) nAChR. Our data show for the first time that APS12-2 blocks neuromuscular transmission by a non-depolarizing mechanism through an action on postsynaptic nAChRs of the skeletal neuromuscular junction.


Effects of Radiotherapy in Coronary Artery Disease.
This review describes the effects of radiotherapy (RT) on coronary artery disease, its mechanisms, and clinical and laboratory evidence and discusses ways to minimize radiation-induced coronary atherosclerosis. Radiation-induced cardiac toxicity is known in patients undergoing thoracic RT. One of the damages occurs in the coronary arteries, with accelerated atherosclerosis manifesting decades later. There is clinical and laboratory evidence of coronary damage in retrospective studies, systematic reviews, and meta-analyses. Clinical studies have shown that RT cardiotoxicity occurs decades after radiation, regardless of chemotherapy, and may occur earlier in patients with pre-existing risk factors or disease. The pathogenesis of radiation-induced coronary artery disease is complex and multifactorial, including endothelial dysfunction, altered vascular tone, hemostatic imbalance, and inflammatory activation. Some factors are responsible, such as mean heart dose, RT chest site, patient position, techniques, and breathing maneuvers. There are approaches to reduce radiation-induced cardiac toxicity. Among them, besides the mentioned factors, metformin and anti-inflammatory agents can minimize coronary damage, with impact on morbidity and mortality.


Muscle shear wave elastography in idiopathic inflammatory myopathies: a case-control study with MRI correlation.
To investigate muscle stiffness in patients with idiopathic inflammatory myopathies (IIM) using shear wave elastography (SWE) and to correlate the results with muscle strength and MRI features of myositis. Muscle shear wave velocity (SWV) was measured in 23 active IIM patients (13 females, mean age 50.4 ± 16.1 years) and 23 matched healthy controls (13 females, mean age 50.7 ± 16.2 years). The investigated muscles included the vastus lateralis (VL), rectus femoris (RF), vastus medialis (VM) vastus intermedius (VI), biceps femoris (BF), semitendinosus (ST), semimembranosus (SM) and the biceps brachii (BB) scanned during relaxed resting and passive stretching positions. Participants performed multiple tests to evaluate their muscle strength. IIM patients had a thigh MRI to assess degrees of oedema, fatty infiltration and atrophy. In the resting position, IIM patients had a 12.9-22.2% significantly lower SWV (p < 0.05) for the quadriceps and hamstrings, but not BB. There was no difference during passive stretching. The SWV for VL, VI and BF showed moderate correlations with the muscle strength tests ranging from r = 0.47 to r = 0.70 (all p < 0.05). Lower SWV was associated with greater MRI scores of oedema (p = 0.001) and atrophy (p = 0.006). However, SWV did not correlate with fatty infiltration (r < 0.3; p = 0.28), creatine kinase (r = 0.28; p = 0.19) or disease duration (r = 0.26; p = 0.24). Shear wave elastography may detect abnormal reduced thigh stiffness in IIM patients. SWE measurements were significantly associated with muscle weakness and MRI signs of oedema and atrophy. Future research should investigate this new technology for monitoring disease activity.


A pilot study of predictive markers of chemotherapy-related amenorrhea among premenopausal women with early stage breast cancer.
Premenopausal women treated for early stage breast cancer (ESBC) are at risk for chemotherapy-related amenorrhea (CRA). Prospectively-validated, predictive markers of CRA are needed. Premenopausal women with ESBC and planned chemotherapy (>/= 25% risk of amenorrhea) were evaluated. Follicle stimulating hormone (FSH), estradiol, Inhibin A and B, anti-Müllerian hormone (AMH), and quality of life (QOL) were prospectively evaluated pre-, post-, 6 months and 1 year post-chemotherapy and correlated with age and menstrual status. CRA was defined as absence of menses 1 year post-chemotherapy. Forty-four women were evaluated at the time of analysis. Median age at diagnosis and FSH 1 year post-chemotherapy were higher among women with CRA (44 yrs [33-51] vs. 40 yrs [31-43]; p = 0.03; 39.8 vs. 5.0 mLU/mL, p = 0.0058, respectively). Median estradiol 1 year post-chemotherapy was higher among women who resumed menses (108.3 vs. 41.3 pg/mL, p = 0.01). Pre-chemotherapy median Inhibin B and AMH were lower among women with CRA (33.2 vs. 108.8 pg/mL; p = 0.03; 0.16 vs. 1.09 ng/mL, p = 0.02, respectively). The risk of CRA was increased among women with lower pre-chemotherapy Inhibin B (RR = 1.67, p = 0.15) and AMH (RR = 1.83, p = 0.05). Amongst women whose pre-chemotherapy Inhibin B and AMH values were below the median, the incidence of CRA was 87.5%. RESULTS indicate that pre-chemotherapy Inhibin B and AMH are lower among women experiencing CRA and may be predictive of CRA among premenopausal women facing chemotherapy for ESBC.


Past year non-medical opioid use and abuse and PTSD diagnosis: Interactions with sex and associations with symptom clusters.
Few studies have examined the associations between posttraumatic stress disorder (PTSD) and non-medical opioid use (NMOU), particularly in general U.S. We analyzed data from wave 2 of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC), a nationally representative sample of non-institutionalized adults, to examine (1) the relationship between PTSD diagnosis with NMOU, Opioid Use Disorder diagnosis, and average monthly frequency of NMOU; and (2) the relationship between PTSD symptom clusters with NMOU, Opioid Use Disorder diagnosis, and average monthly frequency of NMOU. We also explored sex differences among these associations. In the adjusted model, a past year PTSD diagnosis was associated with higher odds of past year NMOU for women and men, but the association was stronger for women. In addition, PTSD was associated with higher odds of an Opioid Use Disorder diagnosis for women, but not for men. With regard to the relationship between specific symptom clusters among those with a past year PTSD diagnosis, important sex differences emerged. For women, the avoidance symptom cluster was associated with higher odds of NMOU, an Opioid Use Disorder diagnosis, and higher rate of average monthly frequency of NMOU, while for men the arousal/reactivity cluster was associated with higher odds of NMOU, an Opioid Use Disorder diagnosis, and a higher rate of average monthly frequency of NMOU. In addition, for men, the avoidance symptom cluster was associated with higher odds of an Opioid Use Disorder diagnosis, but a lower rate of average monthly frequency of NMOU. Results add to the literature showing an association between PTSD and NMOU and suggest that PTSD is more strongly associated with substance use for women than men. Further, results based on individual symptom clusters suggest that men and women with PTSD may be motivated to use substances for different reasons.


Effects of age and oligoasthenozoospermia on telomeres of sperm and blood cells.
How do age and normo- or oligoasthenozoospermia affect telomere length dynamics in spermatozoa and blood? Sperm and blood samples were collected from a cohort of 37 men aged 25 and under and 40 men aged 40 and over, with either normozoospermia (NZ) or oligoasthenozoospermia (OAZ). Telomere length was evaluated using quantitative fluorescence in-situ hybridization. Telomerase mRNA (TERC and TERT) and shelterin (TRF1) gene expression were analysed using quantitative real-time polymerase chain reaction. TRF1 protein immunoreactivity was also evaluated using immunofluorescence. Mean sperm telomere length (STL) increased with age in the NZ group; older NZ men accumulated the longest telomeres (P < 0.001). In peripheral blood mononuclear cells (PBMC), mean telomere length decreased with age in NZ groups, although not reaching statistical significance. Interestingly, the younger OAZ group had the shortest mean telomere length (versus young NZ, P = 0.0081; versus old NZ, P = 0.0116; versus old OAZ, P = 0.0009) and accumulated the highest percentage of short telomeres compared with the other groups (overall P = 0.0017). Analysis of TERC and TERT mRNA expression in spermatozoa and PBMC did not show significant differences among groups. Statistically significant positive correlations were found between STL and seminal parameters in younger NZ men (P = 0.009 for sperm count and P = 0.007 for total progressive motility). Protein immunoreactivity of TRF1 in blood was not significantly different in all groups analysed. The OAZ group did not show the increase of STL with age that is seen in NZ individuals, suggesting that telomere length elongation mechanisms fail in OAZ patients. In PBMC, younger OAZ individuals showed significantly shorter mean telomere length, suggesting that this parameter could be a good biomarker of OAZ in younger OAZ patients. Telomerase gene and TRF1 mRNA expression and TRF1 protein immunoreactivity did not differ significantly between groups, and so these factors cannot be used as OAZ biomarkers.


Determination of protease subsite preference on SPOT peptide array by fluorescence quenching-based assay.
A peptide SPOT array was synthesized on a glass chip and used to determine protease subsite preference. To synthesize a peptide array for positional scanning, the ratio of the isokinetic concentration was determined for every Fmoc-amino acid except Cys. Based on this ratio, a peptide array consisting of Dabcyl-X-X-P(2)-Arg-X-X-X-Lys(FITC) (X: equimolar mixture of 19 amino acids, P(2): one of 19 amino acids) was synthesized on a chitosan-grafted glass chip. Subsequently, the peptide substrates on the array were hydrolyzed by thrombin to screen for subsite specificity using a fluorescence quenching-based assay. The P(2) subsite specificity of thrombin was screened by the fluorescence images obtained after hydrolysis. Pro at the P(2) subsite showed the highest specificity for thrombin based on both the fluorescence quenching-based assay and the solution phase assay. From these results, we confirmed that our mixture-based peptide SPOT array format on the chitosan-grafted glass chips could be used to determine protease subsite preference.


New anti-inflammatory targets for chronic obstructive pulmonary disease.
Chronic obstructive pulmonary disease (COPD) is associated with chronic inflammation of the peripheral airways and lung parenchyma, which leads to progressive obstruction of the airways. Current management with long-acting bronchodilators does not reduce disease progression, and there are no treatments that effectively suppress chronic inflammation in COPD. An increased understanding of the inflammatory processes that are involved in the pathophysiology of COPD has identified several new therapeutic targets. This Review discusses some of the most promising of these targets, including new antioxidants, kinase inhibitors and drugs that target cellular senescence, microbial colonization, epigenetic regulation of inflammatory gene expression and corticosteroid resistance.


Mass grave complexity effects on the minimum number of individuals estimation.
This study analyses the accuracy of the minimum number of individuals (MNI) estimation in the context of commingled human remains recovered from secondary mass graves related to the war in Bosnia in 1995. It is based on data from five secondary mass grave sites of different sizes and different numbers of unassociated body parts. The study is centered on a comparison of MNI estimation from original excavations with the actual number of individuals buried in particular graves, obtained via DNA identification of excavated remains. The aim was to investigate how the complexity of a mass grave reflects on MNI estimation accuracy. In order to quantify mass grave complexity (level of commingling), a ratio between complete bodies and isolated body parts from the same context was introduced. Results show that, in the secondary mass graves involved in the study, MNI estimation inaccuracy varies in the range from 54% to 513% depending on the size of the grave itself and the amount of "loose elements" distributed in it. Correlation between MNI inaccuracy and body to body parts ratio shows a strong relationship indicating that MNI (in)accuracy is largely dependent on the number of loose elements related to complete bodies from the same context.


Suspended nanoparticles in surfactant media as a microextraction technique for simultaneous separation and preconcentration of cobalt, nickel and copper ions for electrothermal atomic absorption spectrometry determination.
The aim of this study was to describe a new method of microextraction based on the suspension of alumina nanoparticles in the surfactant media for simultaneous separation and preconcentration of the ultra-traces of cobalt, nickel and copper ions. In this technique, the alumina nanoparticles were suspended in the non-ionic surfactant solution of Triton X-114. The analytes in the sample solution were adsorbed onto the nanoparticles. After the phase separation based on the cloud point of the mixture at 40 °C, the nanoparticles settled down in the surfactant rich phase. Then 120 μL of nitric acid (3.0 mol L(-1)) was added to the surfactant rich phase which caused desorption of the analytes. Finally, the liquid phase was separated by centrifugation from the nanoparticles and was used for the quantification of the analytes by the electrothermal atomic absorption spectrometry (ETAAS). The parameters affecting the extraction and detection processes were optimized. Under the optimized experimental conditions (i.e. pH∼8, Triton X-114, 0.05% (v/v); temperature 40 °C), a sample volume of 25 mL resulted in the enhancement factors of 198, 205 and 206 and detection limits (defined as 3Sb/m) of 2.5, 2.8 and 2.6 ng L(-1) for Co(II), Ni(II) and Cu(II) respectively. The sorbent showed high capacity for these metal ions (30-40 mg g(-1) sorbent). The method was successfully applied to the determination of the analytes in natural water samples.


[Status of microcirculation in patients with chronic gastritis and its relation to morphofunctional changes in the stomach].
Studies on 74 patients with chronic gastritis showed that the disease was accompanied by disorders of the microcirculatory bed of the bulbar conjunctiva characterized by the appearance of perivascular edema, inhomogeneity of the vascular caliber and coiling, change of arteriolovenular ratios, the formation of vascular glomerules, neglected zones, intravascular aggregation of erythrocytes and microthromboses. These changes were combined with disorders of the end blood flow of the gastric mucosa detected in its specimens. A degree of the above disorders depended on the expression of exacerbation and period of disease, peculiarities of lesion of the gastric mucosa, secretory and motor functions of the stomach.


Counteracting arsenic toxicity: Curcumin to the rescue?
Arsenicosis leads to various irreversible damages in several organs and is considered to be a carcinogen. The effects of chronic arsenic poisoning are a result of an imbalance between pro- and antioxidant homeostasis, oxidative stress, as well as DNA and protein damage. Curcumin, the polyphenolic pigment extracted from the rhizome of Curcuma longa, is well-known for its pleiotropic medicinal effects. Curcumin has been shown to have ameliorative effects in arsenic-induced genotoxicity, nephrotoxicity, hepatotoxicity, angiogenesis, skin diseases, reproductive toxicity, neurotoxicity, and immunotoxicity. This review aims to summarize the scientific evidence on arsenic toxicity in various organs and the ameliorative effects of curcumin on the arsenic toxicity.


cis-Regulatory networks during development: a view of Drosophila.
Understanding how regulatory networks initiate, maintain and synchronise transcriptional states remains a fundamental goal of developmental biology. Complex patterns of spatio-temporal gene expression are generated through the combined inputs of signalling and transcriptional networks converging on cis-regulatory modules (CRMs). Detailed studies in Drosophila, using transgenic reporter assays and mutagenesis analysis, have dissected the regulatory logic of a number of CRMs. These data have recently been complemented by genome-wide maps of transcription factor binding, revealing an unprecedented view of CRM occupancy and network complexity. The synthesis of data for three well-characterised Drosophila developmental networks reveals emerging themes at both a CRM and a cis-regulatory network level.


The effect of HIV coinfection, HAART and TB treatment on cytokine/chemokine responses to Mycobacterium tuberculosis (Mtb) antigens in active TB patients and latently Mtb infected individuals.
Identification of Mtb specific induced cytokine/chemokine host biomarkers could assist in developing novel diagnostic, prognostic and therapeutic tools for TB. Levels of IFN-γ, IL-2, IL-17, IL-10, IP-10 and MIP-1α were measured in supernatants of whole blood stimulated with Mtb specific fusion protein ESAT-6/CFP-10 using xMAP technology. The study groups were HIV positive TB patients (HIV(+)TB(+)), HIV negative TB patients (HIV(-)TB(+)), HIV positive tuberculin skin test positive (TST+) (HIV(+)TST(+)), HIV negative TST+ (HIV(-)TST(+)), and HIV(-)TST(-) individuals. Compared to HIV(-)TST(-), latent TB infection led to increased levels of IP-10, IFN-γ and IL-17, while levels of IL-2 and IP-10 were increased with active TB. Levels of IFN-γ, IL-17, MIP-1α, and IL-10 were increased in HIV(-)TST(+) individuals compared to HIV(-)TB(+) patients. HIV coinfection decreased the level of IFN-γ, IL-17, IP-10 and IL-2. After six months (M6) of anti-TB treatment (ATT) in HIV(-)TB(+) patients, IFN-γ, IL-10, and MIP-1α levels normalized. After M6 and M18 of ATT plus HAART in HIV(+)TB(+) patients, levels of MIP-1α and IL-10 normalized, while this was not the case for IFN-γ, IL-2, IL-17, and IP-10 levels. In HIV(+)TST(+) patients on HAART, levels of IFN-γ, IL-17, IL-10 and MIP-1α normalized, while no change in the levels of IL-2 and IP-10 were observed. In conclusion, the simultaneous measurement of IFN-γ, IL-17 and IP-10 may assist in diagnosing LTBI; IL-2 and IP-10 may assist in diagnosing active TB; while IFN-γ, IL-17, MIP-1α, and IL-10 levels could help to discriminate LTBI and active TB. In addition, IL-10 and MIP-1α levels could help to monitor responses to TB treatment and HAART.


Endurance training increases the number of endothelial progenitor cells in patients with cardiovascular risk and coronary artery disease.
As regular physical exercise improves endothelial dysfunction and promotes cardiovascular health, we investigated the effect of training on angiogenesis by measuring the number of circulating endothelial progenitor cells (EPC), the level of EPC-mobilizing growth factors and tested vascular function by flow-mediated dilation (FMD) in patients with coronary artery disease (CAD) and cardiovascular risk factors (CVRF). In addition, degradation products of the NO pathway (NOx) were determined. Twenty patients with documented CAD and/or CVRF joined a 12-week supervised running training. Circulating EPCs--defined by the surface markers CD34, KDR and CD133--were measured at baseline and after exercise training by flow cytometry. We found a significant increase in circulating EPCs (2.9+/-0.4-fold increase; P < .0001), which was positively correlated with both, the change of FMD (r = .81, P < .001) and the increase of NOx synthesis (r = .83, P < .001). Plasma VEGF and erythropoietin did not change in response to exercise. However, we observed a positive correlation between the number of EPCs and erythropoietin at baseline (r = .70, P < .01) and after training (r = .73, P < .01). Regular exercise training augments the number of circulating EPCs in patients with CVRF and CAD and is associated with improved vascular function and NO synthesis.


Simultaneous determination of timolol maleate, rosuvastatin calcium and diclofenac sodium in pharmaceuticals and physiological fluids using HPLC-UV.
A novel HPLC-UV method was developed for the simultaneous determination of timolol (TM), rosuvastatin (RST), and diclofenac sodium (DS) in pharmaceuticals, human plasma and aqueous humor using naproxen sodium as internal standard (IS). The target compounds were analyzed on Hypersil BDS C(18) column (250 mm × 4.6 mm, 5 μm), applying 0.2% triethylamine (TEA) and acetonitrile (ACN) (40:60, v/v), in isocratic mode as mobile phase, pH 2.75 adjusted with 85% phosphoric acid at a flow rate of 1 ml/min. The column oven temperature was kept at 45°C and the peak response was monitored at 284 nm after injecting a 50 μl sample into HPLC system. The direct liquid-liquid extraction procedure was applied to human plasma and bovine aqueous humor samples using mobile phase as an extraction solvent after deproteination with methanol. The different HPLC experimental parameters were optimized and the method was validated according to standard guidelines. The recoveries of the suggested method in human plasma were 98.72, 96.04, and 95.14%, for TM, RST, and DS, while in aqueous humor were 94.99, and 98.23%, for TM, and DS, respectively. The LOD values were found to be 0.800, 0.500, and 0.250 ng/ml, for TM, RST, and DS, respectively, while their respective LOQ values were 2.00, 1.50, and 1.00 ng/ml. The co-efficient of variation (CV) were in the range of 0.1492-1.1729% and 1.0516-4.0104%, for intra-day and inter-day studies, respectively. The method was found accurate in human plasma and bovine aqueous humor and will be applied for the quantification of these compounds in plasma, and aqueous humor samples using animal models and in pharmaceuticals.


Magnetic solid-phase extraction of warfarin and gemfibrozil in biological samples using polydopamine-coated magnetic nanoparticles via core-shell nanostructure.
Herein, polydopamine-coated Fe3 O4 spheres were synthesized using a very simple, easy, cost-effective, efficient, and fast method. First, magnetic nanoparticles (Fe3 O4 ) were synthesized and were followed by accommodating polydopamine on the surface of the prepared Fe3 O4 . The prepared polydopamine-coated Fe3 O4 spheres were utilized as a sorbent in magnetic solid phase extraction of gemfibrozil and warfarin (as the model analytes). The extracted model analytes were desorbed by a suitable organic solvent and were analyzed by high-performance liquid chromatography. Under optimized condition, the linearity of the method was in the range of 0.1-200.0 μg/L for the selected analytes in water. The limits of detection were calculated to be in the range of 0.026-0.055 μg/L for warfarin and gemfibrozil, respectively. The limits of quantification were calculated to be in the range of 0.089-0.185 μg/L. The inter-day and intra-day relative standard deviations were determined to be in the range of 1.4%-3.3% in three concentrations in order to calculate the method precision. Furthermore, the enrichment factors were found to be 78 and 81 for warfarin and gemfibrozil, respectively. Moreover, the calculated absolute recoveries were between 78% and 81%. The obtained recoveries indicated that the method was useful and applicable in complicated real samples.


Narrow Band Imaging Endoscopy of the Nasopharynx for Malignancy: An Inter- and Intraobserver Study.
To assess interobserver agreement and intraobserver reproducibility when assessing the nasopharynx for malignancy under white light and narrow band imaging endoscopy because the decision to biopsy hinges on the examiner's perceived chance of malignancy. An interobserver and intraobserver agreement study utilizing white light and narrow band endoscopic images of the nasopharynx. The setting was an academic referral hospital. Participants were 156 adults with suspected nasopharyngeal carcinoma who underwent white light and narrow band imaging endoscopy and biopsy. Images of the nasopharynges were subsequently scored for malignancy by four otolaryngologists. The nasopharynx was scored on 4-point scales under white light and narrow band imaging endoscopy for the likelihood of malignancy or abnormality, respectively. Intraclass correlation coefficients for intraobserver agreement for nasopharyngeal malignancy for four observers under white light were 0.86, 0.89, 0.79 and 0.88 (mean 0.855), respectively; and under narrow band imaging they were 0.64, 0.68, 0.64, and 0.66 (mean 0.655), respectively (all P values < 0.001). The coefficient for interobserver reliability under white light was 0.79 (95% confidence interval [CI] 0.76-0.82; P < 0.001), which indicated strong agreement. The coefficient for interobserver reliability under narrow band imaging was 0.56 (95% CI 0.50-0.61; P < 0.001), which indicated moderate agreement. Intraobserver and interobserver agreement for nasopharyngeal malignancy was strong on white light endoscopy but only moderate on narrow band imaging endoscopy. Agreement may be improved by adopting a standard set of assessment guidelines, including an objective detailed morphological analysis under white light and vasculature analysis under narrow band imaging. 2a Laryngoscope, 129:1374-1379, 2019.


The expression of carcinoma-associated antigens and blood-group-related antigens in rectal carcinoids.
The immunohistochemical expression of blood-group substances and carcinoma-associated antigens were compared in rectal carcinoids and adenocarcinomas. Rectal carcinoid tumors, in contrast to rectal carcinomas, were consistently negative for CEA, gastrointestinal cancer antigen GICA (or CA 19-9), and carcinoma-associated antigen CA-50 (except in one case where less than 10 percent of the cells expressed CA-50). The carcinoids and rectal carcinomas extensively expressed blood-group substance A, B, and H, Lewis B antigen, and difucosylated carbohydrate antigens (DFCA). Thus, rectal carcinoids and adenocarcinomas possess both similar and different tumor antigen profiles. The occurrence of discrepant antigen determinants may be used in the differential diagnosis of these two types of tumors. The coexpression of blood-group substance A, B, and H, Lewis B antigen, and DFCA is consistent with the opinion that both rectal carcinomas and carcinoids have a common entoderm origin, but carcinoids are considered to rise from the endocrine-differentiated and the adenocarcinomas from the nonendocrine-differentiated enterocytes.


Chromoxane cyanine R. II. Staining of animal tissues by the dye and its iron complexes.
The staining properties of chromoxane cyanine R (Colour Index No. 43820, Mordant blue 3; also known as eriochrome cyanine R and solochrome cyanine R) have been studied. Used alone, the dye imparted its red colour to nuclei, cytoplasm and collagen. The dye was extracted by mild alkali but not by acids. Stainability required ionized amino groups in the tissue, and there was also evidence for non-ionic binding of the dye. The colours obtained by staining with mixtures of chromoxane cyanine R and ferric chloride varied with the molar iron:dye ratio and with the pH. Useful staining was seen only between pH 1 and 2. The tissues were coloured either all blue (when Fe:dye was high), or both red and blue (when Fe:dye was low). Lower pH favoured the deposition of red, higher pH the deposition of blue colour. The red was mainly in cytoplasm, blue in nuclei and myelin. Collagen fibres were red or purple, depending on pH and iron:dye ratio. Red colours were differentiated by acid and changed to blue, but not extracted, by mild alkali. The red substance in the stained sections was clearly not the free dye, so it was probably an iron-dye complex. From the effects of various differentiating agents, it was deduced that the red and blue dye-metal complex molecules were bound to the tissue by the dye moiety, not by interposition of iron atoms. Staining by the complexes of iron(III) with chromoxane cyanine R did not involve nucleic acids or other polyanions or the amino groups of proteins. There was evidence for only non-ionic binding of both red and blue complexes. It is suggested that the red colour in sections stained by solutions with low iron:dye ratio is due to a simple carboxylate complex, [ Fe2H (dye)]-. The blue colour would then result from withdrawal of a proton from the red complex to give [Fe2(dye)]2-. The bases that remove the protons may be arginine-rich nucleoproteins of nuclei and phospholipid bases of myelin. Techniques are described for informative simultaneous staining in two colours, and for the selective staining of either nuclei or myelin.


Parallel suspension polymerization for high-throughput resin synthesis.
A simple, straightforward approach for parallel suspension polymerization is described. This technique utilizes equipment common to most organic chemistry laboratories and should facilitate the custom synthesis of new polymers.


A simple gravimetric method for estimation of plasma fibrinogen.
The study was undertaken to evaluate a new method of estimating plasma fibrinogen levels, gravimetrically using calcium chloride in albino rats. The results were compared with the standard method in which thrombin was used as clotting agent and were found to be statistically not significant. Advantages of using calcium chloride instead of thrombin have been discussed.


Correlation of an enzyme immunoassay with the radioimmunoassay for CA-125.
Serum CA-125 concentrations from 60 women were determined by radioimmunoassay and an enzyme immunoassay. Correlation of the CA-125 values obtained by the two methods indicated a linear relationship between 13 and 73 U/ml, lower values in the enzyme immunoassay, and a lower sensitivity of the enzyme immunoassay as compared with the radioimmunoassay.


Superiority of Brain and Spinal Injury Center Score for Assessing Injury Severity and Predicting Prognosis in Patients with Acute Traumatic Spinal Cord Injury.
The goal of this study was to evaluate the interrelationship between different magnetic resonance (MR) imaging measures and their validity in assessing the severity of acute traumatic spinal cord injury (tSCI) and predicting neurological outcomes. We performed a preoperative multicenter cohort study of 89 patients with acute tSCI and preoperative MR imaging within 24 h after injury. We assessed several MR imaging measures of injury, including axial grade (Brain and Spinal Injury Center [BASIC] score), sagittal grade, length of injury, maximum canal compromise (MCC), and maximum spinal cord compression (MSCC). Principal component analysis (PCA) was applied to evaluate the interrelationship between different MR imaging measures. Spearman correlation and regression analyses were applied to assess injury severity and predict neurological impairment. The severity was assessed by the American Spinal Injury Association Impairment Scale (AIS) at admission, while neurological outcome was defined by AIS grade change at 6 weeks, AIS grade and SCIM score at 1 year after surgery. The PCA identified 2 clusters of MR imaging variables related to 1) measures of intrinsic cord signal abnormality (BASIC score, sagittal grade and length of injury) and 2) measures of extrinsic cord compression (MCC and MSCC). Neurological outcome and injury severity were best accounted for by MR imaging measures of intrinsic cord signal abnormalities, with the BASIC score representing the most accurate predictor of short-term and long-term neurological outcomes. We determined the superior significance of the BASIC score in assessing injury severity, predicting early AIS improvement, AIS grade and SCIM score at 1 year compared with other MR imaging measures.


Side-branch occlusion after rotational atherectomy of in-stent restenosis: incidence, predictors, and clinical significance.
We evaluated the incidence, predictors, and clinical significance of side-branch occlusion (SBO) after rotational atherectomy (RA) for treatment of in-stent restenosis (ISR) and compared it with those of native coronary artery (NC). RA was performed in 64 patients with 34 ISR (42 side branches) and 30 NC (40 side branches). SBO occurred 14% after RA in ISR group compared with 0% in NC group (P < 0.05), and 33% after adjunctive balloon inflation in ISR group compared with 2.5% in NC group (P < 0.01). Non-Q myocardial infarction developed in seven patients in ISR group and four patients in NC group (P = NS). The presence of significant side-branch (SB) ostial disease (OR = 4.7, P < 0.05) and ISR lesions (OR = 15.5, P < 0.05) were the only independent predictors of SBO by multivariate analysis. The incidence of SBO is higher after RA of ISR than RA of NC and may be associated with an increased risk of non-Q myocardial infarction.


CO2-responsive deep eutectic solvents for the enhanced extraction of hesperidin from Fertile orange peel.
Hesperidin, also known as vitamin P, is widely studied for its distinctive potential in food and pharmaceutical industries. This work focuses on the research of CO2-responsive deep eutectic solvents (DESs) used as recyclable extractants for efficient extraction of hesperidin from Fertile orange peel. Reversible phase transformation of DES solution was achieved by bubbling CO2/N2. The maximum extraction yield of 22.39 mg/g was obtained for hesperidin under the following conditions: DES-6 (triethanolamine: 4-methoxyphenol = 1:1) used as extractant, water content of 35 wt%, solid-liquid ratio of 1:60 g/mL, extraction temperature of 25 °C, and ultrasonic time of 25 min, which was much higher than that extracted by methanol. Hesperidin of 74.38% was recovered in top phase after CO2 triggering. Density function theory (DFT) results indicated that hydrogen and π-π bonds were the main factors affecting hesperidin extraction. This study provides a new idea for extracting natural bioactive compounds using recyclable extractants.


Searching for antigen B genes and their adaptive sites in distinct strains and species of the helminth Echinococcus.
Twenty-seven PCR-derived antigen B (AgB) nucleotide sequences from four Echinococcus species (Echinococcus granulosus, Echinococcus multilocularis, Echinococcus oligarthrus and Echinococcus vogeli) were aligned with 78 already published sequences, to generate a maximum likelihood phylogeny of the AgB multigene family. The phylogenetic analysis confirms that the family is constituted by four groups of genes present in each one of the four species (AgB1, AgB2, AgB3 and AgB4), and suggests that it originated by ancient duplication events preceding speciation within the genus. AgB5 sequences, which had been formerly suggested to correspond to a putatively new AgB subunit, cluster with AgB3. Likelihood tests suggest that AgB gene evolution may have been driven by heterogeneous selection pressures acting on particular AgB1, AgB3 and AgB4 codons. No selection is detected in AgB2. We discuss implications of our findings in terms of AgB biology and its use as a diagnostic tool.


Left ventricular outflow tract obstruction: an indication for intraoperative transesophageal echocardiography.
Transesophageal echocardiography (TEE) provides detailed anatomic imaging of both discrete and complex forms of left ventricular outflow tract (LVOT) obstruction, and Doppler techniques provide additional information regarding the site, mechanism, and severity of the obstruction. Because the transaortic surgical approach to LVOT obstruction often provides limited direct visualization during surgery, we sought to evaluate the utility of intraoperative TEE during surgery for LVOT obstruction. We tested the hypotheses that intraoperative TEE would (1) be useful in defining the level and nature of LVOT obstruction, (2) serve to direct the surgical approach, (3) define the adequacy of relief of LVOT obstruction, and (4) detect surgical complications. Study population consisted of a consecutive series of 27 infants and children undergoing surgery for LVOT obstruction. Patient age ranged from 0.5 to 17.9 years, and weight from 5.4 to 71.2 kg. In 14 patients LVOT obstruction resulted from a discrete membrane, whereas 13 had complex forms of LVOT obstruction. Fully anesthetized and monitored patients were examined with 5 MHz TEE probes appropriate to the size of the patient. In the 14 patients with discrete LVOT obstruction, discrete membranes were identified by TEE in all; gradients ranged from 36 to 75 mm Hg. In 13 of 14 patients, postbypass TEE demonstrated removal of the membrane and excellent relief of gradients. In one of these patients, TEE demonstrated a small ventricular septal defect acquired during resection; the patient was returned to bypass for closure. In one patient, return to bypass for further resection of LVOT obstruction was prompted by TEE demonstration of a high residual gradient. In the 13 patients with complex LVOT obstruction, TEE demonstrated the complexity of LVOT obstruction in all. Gradients ranged from 4 to 95 mm Hg. Although this information was used in surgical planning, five patients had high residual gradients after bypass and underwent further resection. An additional two were returned to bypass for mitral valve replacement. Overall, 8 of 27 patients (29.6%) were returned to bypass based on TEE demonstration of residual anatomic or hemodynamic abnormalities. This occurred significantly more frequently in complex LVOT obstruction than in discrete LVOT obstruction (p = 0.045). We conclude that intraoperative TEE has substantial utility in the demonstration of site, mechanism, and severity of LVOT obstruction and for surgery designed to relieve LVOT obstruction. We believe that TEE should be an integral part of surgical management of LVOT obstruction.