Control of the position of RNase P-mediated transfer RNA precursor processing.
Two Bacillus subtilis tRNA(His) precursors (Green, C. J., and Vold, B. S. (1988) J. Biol. Chem. 263, 652-657) were processed by Escherichia coli RNase P in the presence of varying [Mg2+]. The wild type precursor was processed under all conditions to afford a single tRNA product containing 8 base pairs in the acceptor stem. In contrast, the position of processing of a mutant tRNA(His) precursor (containing a G27----A27 alteration) was shown to be condition-dependent. Processing occurred at A27 under conditions consistent with formation of an A27-C100 base pair in the acceptor stem but at G28 under conditions that disfavored base pair formation. The ability to control the site of RNase P-mediated tRNA precursor processing is unprecedented and permits analysis of the chemical factors that promote processing.


Nutritional dependence of the effect of estrogen on fat cell lipoprotein lipase.
We investigated the effects of ethynylestradiol (EE) at low dose (1.2 micrograms/day) injected s.c. for 10 days on lipoprotein lipase (LPL) in fat cells of female rats fed a standard diet (5% lipid, 49.5% glucid, 23.5% protein) as a function of the nutritional state. EE caused a 150% increase in LPL activity in the fed state, and a 65% decrease in the fasting state, resulting in a large increment in the physiological feeding-fasting difference. Feeding the rats a diet supplemented with 20% lard reversed the estrogen-dependent LPL increase in the fed state. Under all experimental conditions, EE caused a depletion of fat stores and an increase in plasma levels of triacyglycerol.


[Surgical prognosis in idiopathic vitreomacular syndrome and epimacular membrane].
The natural history shows less progression for epimacular membrane than for vitreomacular traction syndrome. We tested the hypothesis that the surgical prognosis in idiopathic cases is also better for epimacular membrane. This retrospective study investigated a consecutive series of 63 epimacular membrane cases (group I) and 25 vitreomacular traction syndrome cases (group II) that were operated on and followed up for a minimum of 6 months. Eyes that had undergone previous surgery or had posterior or peripheral retinal lesions were excluded. In bilateral macular surgery cases, only the first eye was included. The outcome measures were far and near visual acuities preoperatively and 6 months after surgery, taking into account the crystalline lens condition, the incidence of retinal tears, detachments, and epimacular membrane recurrences. At 6 months, if the lens was stable or operated on, the visual acuity showed at least a two-line improvement in 100% of the cases (12/12) in group I, and 60% (3/5) in group II. The incidence of retinal detachment and tears was 1.5% (1) and 1.5% (1), respectively, in group I, and 8% (2) and 4% (1), respectively, in group II. Recurrence of an epimacular membrane was observed in 6% of the cases (4) in group I and 8% (2) in group II. In idiopathic cases, the absence of preoperative vitreomacular adhesion seems to carry a better surgical prognosis for epimacular membrane than vitreomacular traction syndrome.


Blood Eosinophil Count as a Predictor of Lung Function Decline in Healthy Individuals.
Little is known about the effect of blood eosinophil count (BEC) on a decline in lung function in healthy individuals. Using a well-established health screening database, we assessed the associations between BEC and a decline in lung function, measured as the forced expiratory volume in 1 second (FEV1). Serial BEC and FEV1 data were analyzed using linear mixed models adjusted for gender, height, and smoking status. The association between BEC consistency and a decline in FEV1 was evaluated in subpopulation analyses. A total of 4634 individuals were enrolled. The mean number of health screenings was 7.49 over an average of 11.74 years of observation. A higher log2-transformed BEC was significantly associated with a greater decline in FEV1 that was stronger in nonsmokers (P = 8.56 × 10-8) than in smokers (P = 1.52 × 10-3). In subpopulation analyses of 2018 individuals with consistent BECs, those with BECs consistently ≥100/μL (P = 4.58 × 10-6), ≥200/μL (P = 3.53 × 10-7), and ≥300/μL (P = 1.12 × 10-3) had a significantly higher dose-dependent FEV1 decline than those with BECs consistently <100/μL. A BEC threshold of 100/μL in nonsmokers and 200/μL in smokers may predict an accelerated decline in FEV1. BEC is associated with a decline in FEV1, and a consistently high BEC is an independent risk factor for an accelerated decline in FEV1. These results suggest the use of the BEC to identify healthy individuals at high risk for developing chronic lung disease, which in turn may enable a tailored preventive strategy.


Identification of DNA methylation-driven genes and construction of a nomogram to predict overall survival in pancreatic cancer.
The incidence and mortality of pancreatic cancer (PC) has gradually increased. The aim of this study was to identify survival-related DNA methylation (DNAm)-driven genes and establish a nomogram to predict outcomes in patients with PC. The gene expression, DNA methylation database, and PC clinical samples were downloaded from TCGA. DNAm-driven genes were identified by integrating analyses of gene expression and DNA methylation data. Survival-related DNAm-driven genes were screened via univariate, least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analyses to develop a risk score model for prognosis. Based on analyses of clinical parameters and risk score, a nomogram was built and validated. The independent cohort from GEO database were used for external validation. A total of 16 differentially expressed methylation-driven genes were identified. Based on LASSO Cox regression and multivariate Cox regression analysis, six genes (FERMT1, LIPH, LAMA3, PPP1R14D, NQO1, VSIG2) were chosen to develop the risk score model. In the Kaplan-Meier analysis, age, T stage, N stage, AJCC stage, radiation therapy history, tumor size, surgery type performed, pathological type, chemotherapy history, and risk score were potential prognostic factors in PC (P < 0.1). In the multivariate analysis, stage, chemotherapy, and risk score were significantly correlated to overall survival (P < 0.05). The nomogram was constructed with the three variables (stage, chemotherapy, and risk score) for predicting the 1-year, 2-year, and 3-year survival rates of PC patients. Nomogram performance was assessed by receiver operating characteristic (ROC) curves and calibration curves. 1-year, 2-year and 3-year AUC of nomogram model was 0.899, 0.765 and 0.776, respectively. In our study, we successfully identified the six DNAm-driven genes (FERMT1, LIPH, LAMA3, PPP1R14D, NQO1, VSIG2) with a relationship to the outcomes of PC patients. The nomogram including stage, chemotherapy, and risk score could be used to predict survival in PC patients.


A novel one-shot anastomotic stapler prototype for coronary bypass grafting on the beating heart: feasibility in the pig.
The nonpenetrating, arcuate-legged clip has proved its ability to provide a high-quality microvascular anastomosis. This study assessed the feasibility of constructing a coronary end-to-side anastomosis on the beating heart with a novel mechanical, sutureless anastomotic device that applies 12 circumferential clips simultaneously. In 14 consecutive pigs (70-90 kg), the left internal thoracic artery (diameter, 3 mm) was grafted to the left anterior descending coronary artery (diameter, 3 mm) by means of a one-shot anastomotic stapler prototype. Endothelial denudation, medial necrosis, and intimal hyperplasia were analyzed quantitatively and compared with those seen in conventionally sutured anastomoses (n = 4). In 8 of 14 anastomoses, the one-shot anastomotic stapler successfully applied all 12 clips circumferentially across the everted arteriotomy edges. In the remaining, either 1 (n = 4) or 3 and 4 adjoining malaligned clips had to be replaced manually with a single-clip applicator. Coronary occlusion was limited to approximately 3 minutes. At follow-up, all anastomoses were patent angiographically. At 2 days, in 2 of 7 cases, a local coronary dissection was observed, and there was a considerable loss of endothelial cells and medial damage. At 28 days, however, minimal intimal hyperplasia was seen at the anastomotic lining, although more pronounced when compared with conventionally sutured anastomoses. The one-shot anastomotic stapler prototype enabled short-occlusive (3 minutes), sutureless end-to-side grafting on the beating porcine heart. In spite of early endothelial and medial damage and 2 local dissections, all anastomoses remained patent with minimal intimal hyperplasia at 4 weeks.


Upregulated hexokinase 2 expression induces the apoptosis of dopaminergic neurons by promoting lactate production in Parkinson's disease.
Parkinson's disease (PD) is characterized by impaired mitochondrial function and decreased ATP levels. Aerobic glycolysis and lactate production have been shown to be upregulated in dopaminergic neurons to sustain ATP levels, but the effect of upregulated glycolysis on dopaminergic neurons remains unknown. Since lactate promotes apoptosis and α-synuclein accumulation in neurons, we hypothesized that the lactate produced upon upregulated glycolysis is involved in the apoptosis of dopaminergic neurons in PD. In this study, we examined the expression of hexokinase 2 (HK2) and lactate dehydrogenase (LDH), the key enzymes in glycolysis, and lactate levels in the substantia nigra pars compacta (SNpc) of a MPTP-induced mouse model of PD and in MPP+-treated SH-SY5Y cells. We found that the expression of HK2 and LDHA and the lactate levels were markedly increased in the SNpc of MPTP-treated mice and in MPP+-treated SH-SY5Y cells. Exogenous lactate treatment led to the apoptosis of SH-SY5Y cells. Intriguingly, lactate production and the apoptosis of dopaminergic neurons were suppressed by the application of 3-bromopyruvic acid (3-Brpa), a HK2 inhibitor, or siRNA both in vivo and in vitro. 3-Brpa treatment markedly improved the motor behaviour of MPTP-treated mice in pole test and rotarod test. Mechanistically, lactate increases the activity of adenosine monophosphate-activated protein kinase (AMPK) and suppresses the phosphorylation of serine/threonine kinase 1 (Akt) and mammalian target of rapamycin (mTOR). Together, our data suggest that upregulated HK2 and LDHA and increased lactate levels prompt the apoptosis of dopaminergic neurons in PD. Inhibition of HK2 expression attenuated the apoptosis of dopaminergic neurons by downregulating lactate production and AMPK/Akt/mTOR pathway in PD.


Morbid obesity and short-term complications following acetabular fracture surgery: A comparative cohort study.
Obesity is an epidemic facing the United States affecting nearly 40% of the population (93.3 million adults). The objective of this study was to compare early perioperative complications in patients with a normal BMI to patients who are pre-obese, obese, and morbidly obese. The study was conducted at a Level-I trauma center. Patients were separated into 4 groups based on their BMI. Group 1 had a BMI < 25 (normal), Group 2 had a BMI between 25-29.9 (pre-obesity), Group 3 had a BMI between 30-39.9 (obese), and Group 4 had a BMI ≥40 (morbidly obese). Outcome variables included total operative time (OT), estimated blood loss (EBL), length of stay (LOS), and early medical and surgical complications. A comparison between groups was performed for each outcome variable and surgical complication. We identified 333 patients and the number of patients in Groups 1-4 were 86, 96, 121, and 30, respectively. The average BMI for Groups 1-4 was 22.3, 27.3, 35.9, and 44.9, respectively (p < 0.001). OT, EBL, and LOS did not differ between groups or between the surgical approach utilized. There were no significant relationships when comparing complication rates between groups. Patients in Group 4 experienced significantly more PE compared to patients in Group 2 (p=0.01). Additionally, patients in Group 4 experienced a significantly more PE than patients in Groups 1 and 2 combined (p<.01). The relative risk of having a PE if BMI is ≥40, compared to a BMI <30 is 18.40 (95% CI = 1.98 - 171.13). The PEs were not fatal in all cases. In the treatment of the obese and morbidly obese with acetabular fractures, we find that these cohorts are not at a greater risk of wound complications or infection. The higher rate of pulmonary embolism seen in the morbidly obese should be considered when evaluating these patients for appropriate thromboembolic prophylaxis.


Initial lesions of HIV-related Kaposi's sarcoma--a histological, immunohistochemical, and ultrastructural study.
Kaposi's sarcoma (KS) in human immunodeficiency virus infection (HIV) has become a rather frequent manifestation of the previously rare disease with fatal outcome. Initial lesions of KS were studied by means of histopathology, immunohistology, and electron microscopy in order to define the earliest alterations. The histopathological changes of initial lesions were distinct, consisting of (1) discrete proliferation of capillary vessels, (2) dissection of collagen by proliferating spindle cells which formed slits, (3) atypical spindle cells arranged in an Indian file pattern, and (4) the lack of any inflammatory cellular infiltrate. Double staining with antibodies against vimentin and immunohistochemical markers for endothelial cells revealed that slits forming vimentin-positive spindle cells displayed laminin, factor VIII, and PAL-E. Atypical vimentin-positive spindle cells arranged in an Indian file pattern inconsistently expressed laminin and factor VIII, but not PAL-E. KS cells rarely stained with the lectin UEA I, not even in case of less advanced dedifferentiation. Electron microscopy showed gradual transformation between spindle cells forming slits and those having lost the ability to form incomplete vessel walls. The present findings support the view that KS develops from the endothelial cells of the blood vessels. The proliferation of atypical endothelial cells as early as in initial lesions and the lack of inflammation favors the primary neoplastic genesis of KS.


Nurturing a precious commodity. Trustee recruits.
Today's trustees have to be sharper and work harder than ever before. Where will the next crop of health care trustees come from? And how can hospital boards find, recruit and grow the increasingly more sophisticated level of talent they need?


Traditional and alternative natural therapeutic products used in the treatment of respiratory tract infectious diseases in the eastern Catalan Pyrenees (Iberian Peninsula).
Respiratory tract diseases, including mild troubles, such as the common cold, and also life-threatening ones such as bacterial pneumonia and lung cancer, are very important in terms of mortality, incidence, prevalence and costs. Classical medicine has undoubtedly addressed these illnesses, but the body of knowledge generated by alternative approaches, among which folk medicine plays an important role, is not at all negligible. In this context, we performed an ethnobotanical study in a Catalan region of the eastern Pyrenees, northeast Iberian Peninsula, in order to assess the popular knowledge on useful plants. We present here the data concerning pharmaceutical uses of plants devoted to respiratory illnesses. A total of 160 informants (94 women and 66 men, born between 1915 and 1988) were interviewed during 102 semi-structured interviews. Voucher specimens were collected, and then processed and deposited in the herbarium BCN. We collected information about 99 plant taxa (94 species - some of them with subspecies - of 85 genera belonging to 50 families) popularly employed to prevent or treat respiratory troubles. The degree of reliability of uses is high, as indicated for instance by an informant consensus factor of 0.83 and by high medicinal importance indexes for many taxa. In addition, we have recorded information on 14 animal and four mineral products also used against respiratory ailments, this constituting the first ethnopharmacological work in the Catalan linguistic area to report plant, animal and mineral remedies, and one of the very few in the Iberian Peninsula involving the study of ethnozoological medicines. The data collected show a high degree of consistency and indicate a remarkable persistence of folk knowledge on plant uses. The anticatarrhal, antitussive and for sore throat are the most valuable uses. This research could be the starting point for further research aiming to obtain products that may generalise the alternative medical uses here raised at a local level. Phytochemical and pharmacological studies on some of the plants quoted here - of which we could provide material to potentially interested researchers - would be useful first steps in this process.


Risk assessment of drinkable water sources using gross alpha and beta radioactivity levels and heavy metals.
The increase in economic activities as a result of population surge in Dutsin-Ma has culminated into increase in waste and environmental quality degradation. Hence, this study examined the risk associated with different drinking water sources (dam water (DM), borehole water (BW), Hand dug well water (WW) and tap water (TW)) in Dutsin-Ma, Katsina using concentrations of gross alpha (α) and gross beta (β) activity, and heavy metals cadmium (Cd) and lead (Pb) in the water. A total of Thirty six (36) samples were collected from the study area. Standard methods were deployed for the determination of pH, concentration of gross alpha and gross beta activity and concentrations of Cd and Pb in the water samples were done using chemical fraction method. The results of the pH showed values not within the recommended limits for drinking water quality with exception of 8.30 (WW). Also, the measured activity concentrations of gross alpha in all water samples are below 0.1 Bq/L with few exceptions, while the measured activity concentrations of gross beta in 50% of the total water samples collected are higher than 1.0 Bq/L permissible limit. The mean annual dose equivalent all the water sources is higher than 0.1 mSv recommended dose for radionuclides in water, hence the life cancer risk assessment showed higher values, indicating the water are unsafe for drinking. The results in this study showed that Cd and Pb in all the water fractions (mobile, dissolved, total and particulate) are above the WHO recommended limit of 0.003 and 0.01 mg/L in drinking water. Similarly, the hazard index (HI) for the water samples are greater than one (1), hence, a possible concern for potential carcinogenic effect for consumer of the water sources.


Unique functional responses differentially map onto genetic subtypes of dopamine neurons.
Dopamine neurons are characterized by their response to unexpected rewards, but they also fire during movement and aversive stimuli. Dopamine neuron diversity has been observed based on molecular expression profiles; however, whether different functions map onto such genetic subtypes remains unclear. In this study, we established that three genetic dopamine neuron subtypes within the substantia nigra pars compacta, characterized by the expression of Slc17a6 (Vglut2), Calb1 and Anxa1, each have a unique set of responses to rewards, aversive stimuli and accelerations and decelerations, and these signaling patterns are highly correlated between somas and axons within subtypes. Remarkably, reward responses were almost entirely absent in the Anxa1+ subtype, which instead displayed acceleration-correlated signaling. Our findings establish a connection between functional and genetic dopamine neuron subtypes and demonstrate that molecular expression patterns can serve as a common framework to dissect dopaminergic functions.


Bisexual Behavior Among Male Injection Drug Users in New York City.
Drug using men who have sex with men and women (MSMW) may be at high risk for HIV infection and transmitting HIV to sex partners. In 2012, injection drug users (IDUs) were sampled in New York City for the National HIV Behavioral Surveillance cross-sectional study using respondent-driven sampling. Logistic regression was used to calculate crude and adjusted odds ratios (aOR) and 95 % confidence intervals (95 %CI) to determine correlates of bisexual behavior in the past 12 months. Of 333 participants, 47(14.1 %) reported MSMW. Variables independently associated (p < 0.05) with MSMW included bisexual sexual identity (vs. "straight") (adjusted odds ratio (aOR) 92.6; 95 % CI 18.9, 454.5), Bronx residence [vs. Manhattan (aOR 8.4; 95 %CI 1.6,43.7)], past 12 month behaviors of having sex with ≥3 sex partners (aOR 18.1; 95 % CI 3.3,98.4), "sold" sex (aOR 8.5; 95 % CI 2.3, 31.5), "bought" sex (aOR 0.2; 95 % CI 0.1, 0.9), and injection methamphetamine use (aOR 20.5; 95 % CI 3.0, 139.7). MSM IDUs are an important subgroup to consider for HIV interventions, as they may not be reached through HIV prevention programming aimed at MSM.


Preoperative administration of eculizumab to prevent surgery-triggered hemolysis during cesarean section with paroxysmal nocturnal hemoglobinuria.
Eculizumab in pregnancy has been reported to be effective in improving outcomes in patients with paroxysmal nocturnal hemoglobinuria. However, a cesarean section may result in surgery-triggered hemolysis. An additional dose of eculizumab just prior to delivery is an appropriate choice to prevent postoperative hemolysis.


Pinealectomy shortens resynchronisation times of house sparrow (Passer domesticus) circadian rhythms.
In many birds periodic melatonin secretion by the pineal organ is essential for the high-amplitude self-sustained output of the circadian pacemaker, and thus for the persistence of rhythmicity in 24 h oscillations controlled by it. The elimination of the pineal melatonin rhythm, or a reduction of its amplitude, renders the circadian pacemaker a less self-sustained, often highly damped, oscillatory system. A reduction in the degree of self-sustainment of a rhythm should not only increase its range of entrainment but also shorten the resynchronization times following phase-shifts of the zeitgeber. This hypothesis has not yet been directly tested. We therefore carried out the present study in which house sparrows (Passer domesticus) were subjected to both 6-h advance and 6-h delay phase-shifts of the light-dark cycle before and after the pinealectomy, and the rhythms in locomotion and feeding were recorded. The results indicate that following the delay, but not the advance, phase shift, resynchronization times were significantly shorter after pinealectomy. The dependence of resynchronization times on the presence or absence of the pineal organ is not only of theoretical interest but might also be of functional significance in the natural life of birds. A reduction or elimination of the amplitude of the melatonin secretion rhythm by the pineal organ might be responsible for faster adjustment to changes in zeitgeber conditions in nature.


Contamination of environment with heavy metals emitted from automotives.
Interest has arisen in heavy-metal contamination of the environment, mostly because of potential hazards to the health of animals and human (directly and/or indirectly). High levels of heavy metals in soil, plants, and the atmosphere are often related to industries, highways , chemical dumping, impure chemical fertilizers, and pesticides containing metals. An important source of heavy metals, especially lead, is from the combustion of leaded gasoline used for transportation. Other heavy metals associated with transportation include nickel, which is also added to gasoline and is contained in engine parts, zinc, and cadmium from tires, lubricating oils, and galvanized parts such as fuel tanks.


Effect of restaurant types on compensation claims for work-related musculoskeletal disorders in France.
The economic burden of work-related musculoskeletal disorders (WMSDs) is industry specific. The objective was to analyse compensation claims for WMSDs among restaurant workers in France taking into account the type of restaurant. Data for 2014 were obtained from the French National Health Insurance Fund for Salaried Workers. A chi-square test was used to compare claims, incapacity and lost work day rates in different types of restaurant. Prevalence for WMSDs differed significantly by the type of kitchen: collective restaurant (7.2/1000 workers), traditional restaurant (1.7/1000), and fast food restaurant (1.0/1000). There were more male claimants in traditional restaurant workers (51.0%) than in collective restaurant workers (40.1%) but more female claimants in collective restaurant workers (50.1%) than in traditional restaurant workers (39.4%). Permanent incapacity was significantly more prevalent in collective restaurant workers (49.6%), than in traditional (41.9%) and fast food (8.5%) restaurant workers. In collective restaurant workers, as a percentage, claims, permanent incapacity and lost work days increased with age range or work experience. Prevalence for WMSDs and therefore incapacity and lost work days are different according to the type of restaurant. Preventive strategies should take these differences into consideration.


Determination of salmeterol in dried blood spot using an ionic liquid based dispersive liquid-liquid microextraction coupled with HPLC.
A novel analytical method based on the use of a modified dispersive liquid-liquid microextraction (DLLME) technique by ionic liquids has been developed for the first time. This method was applied for the determination of salmeterol in dried blood spot samples from asthmatic patients followed by HPLC system equipped with fluorescence detector. The main novelty of the present work deals with the analysis of salmeterol in dried blood spot with significant advantages with regard to invasive sampling, volume of blood used (<20 μL), storage and transport of biological materials and requirements for special biohazard arrangements. The effects of significant factors in microextraction procedure including extracting and disperser solvents volume, sample pH and salt contents were investigated. Under optimized conditions, the mean recoveries were higher than 90.0% with linear responses about 1.00-500 ng mL(-1) concentration range. The limit of detection (LOD) was 0.30 ng mL(-1) in S/N of 3. Intra-day (n=6) and inter-day (n=3) assay precision showed relative standard deviation lower than 6.0 and 8.5% for studied drug, respectively. The developed microextraction procedure was simpler and faster than conventional extraction techniques and was omitted hazard organic solvents. Finally, the proposed method is suitable for the analysis of salmeterol in dried blood spots from asthmatic patients for therapeutic drug monitoring purpose.


Boron-doped nanocrystalline diamond microelectrode arrays monitor cardiac action potentials.
The expansion of diamond-based electronics in the area of biological interfacing has not been as thoroughly explored as applications in electrochemical sensing. However, the biocompatibility of diamond, large safe electrochemical window, stability, and tunable electronic properties provide opportunities to develop new devices for interfacing with electrogenic cells. Here, the fabrication of microelectrode arrays (MEAs) with boron-doped nanocrystalline diamond (BNCD) electrodes and their interfacing with cardiomyocyte-like HL-1 cells to detect cardiac action potentials are presented. A nonreductive means of structuring doped and undoped diamond on the same substrate is shown. The resulting BNCD electrodes show high stability under mechanical stress generated by the cells. It is shown that by fabricating the entire surface of the MEA with NCD, in patterns of conductive doped, and isolating undoped regions, signal detection may be improved up to four-fold over BNCD electrodes passivated with traditional isolators.


A comparison between ALG and bone marrow transplantation in treatment of severe aplastic anemia.
One hundred patients with severe aplastic anemia were treated and evaluated in a prospective study at our hospital between January 1976 and October 1983. 28 patients had a HLA-identical sibling donor and were treated with bone marrow transplantation. 72 patients without a HLA-identical sibling donor were given antilymphocyte globulin followed by oral low dose androgen therapy. One and a half years to nine years after treatment 13 patients (46%) survive in the transplant group and 53 patients (74%) survive in the second group. All except one in the second group have self-sustaining hematopoiesis without need for transfusions. There is one major difference between the two therapies. Marrow transplantation restores bone marrow function completely and no late hematological complications have been seen in this group. The majority of patients treated with antilymphocyte globulin in contrast have residual abnormalities of hemopoiesis: macrocytosis, mild granulocytopenia and mild thrombocytopenia. Relapse (11 of 72 patients) and clonal hematological disorders, such as paroxysmal nocturnal hemoglobinuria (4 patients) and leukemia (one patient) can occur years after complete bone marrow reconstitution with antilymphocyte globulin. These late disorders are of concern. In spite of this we conclude that antilymphocyte globulin treatment is an effective therapy with low early mortality and morbidity and a high chance for a long sustained remission. Results are better or at least equivalent to bone marrow transplantation and patients with donors should be given the option of transplantation or antilymphocyte globulin.


Interferons induce proteolytic degradation of TRAILR4.
IFNgamma and its transcriptional target tumor necrosis factor (TNF)-related apoptosis inducing ligand (TRAIL) are two major effector molecules of activated CTLs and NK cells. Here, we show that IFNgamma as well as the type I interferon IFNalpha strongly inhibit cell surface expression of the decoy receptor TRAILR4 while having only a moderate inhibitory or even an inducing effect on TRAILR2 and CD95. Interferon-induced inhibition of TRAILR4 expression was blocked by a protease inhibitor cocktail and also by MG132, suggesting that down-regulation of TRAILR4 involves the proteasome. Inhibition of TRAILR4 expression by siRNA sensitized for TRAIL-, but not CD95L-induced apoptosis. Thus, the apoptosis-inducing action of interferons may not only rely on the well-established induction of TRAIL in effector cells but also on concomitant down-regulation of its antagonizing decoy receptor TRAILR4 in target cells.


[Neo-oogenesis in the adult ovary: What do we know?]
For more than a decade, the existence of ovarian stem cells that can contribute to neo-oogenesis in the adult ovary is reported by some teams, challenging the dogma according to which mammalian females are born with a fixed and non-renewed germinal cell pool. The presence of germinal stem cells with mitotic activity suggests the possibility of potential postnatal oogenesis. These cells have both germ-line and stem cell markers in culture. They have been isolated using different strategies and their ability to differentiate into oocytes has been demonstrated since after reintroduction in an ovarian somatic environment, these cells generate follicles capable of producing healthy offspring in rodents. However, many scientists remain skeptical and question the reliability of the methods used. Despite that there is no consensus on the origin of these ovarian stem cells, private companies are now proposing to use their stem cell potential to treat human infertility.


Changes in mucogingival junction after an apically positioned flap with collagen matrix at sites with or without previous guided bone regeneration: A prospective comparative cohort study.
To assess changes in the position of the mucogingival junction (MGJ) after an apically positioned flap (APF) with collagen matrix performed at sites with or without previous guided bone regeneration (GBR). Dental implants were placed with or without GBR (group GBR or non-GBR) depending on the available ridge width in 30 patients with a limited width of keratinized mucosa (MGJ placed more coronally than the expected prosthetic margin). An apically positioned flap with collagen matrix was performed in both groups. Changes in the position of the MGJ from the day of an apically positioned flap up to 1, 3, and 12 months thereafter were assessed on digital scans (primary endpoint). Secondary endpoints were the width and thickness of the keratinized mucosa, and the position of the mucosal margin. The position of the MGJ changed significantly from baseline to the first month, by 5.25 ± 2.10 and 4.40 ± 1.41 mm in groups GBR and non-GBR, respectively. Thereafter, the position remained stable in both groups up to 1 year (changes from baseline of 5.46 ± 2.28 and 4.58 ± 1.92 mm, respectively; p = .34). The position of the mucosal margin did not differ between groups GBR and non-GBR (-1.57 ± 2.04 and -1.75 ± 2.08 mm, respectively; p = .84), nor did the width of the keratinized mucosa (1.20 ± 1.03 and 0.99 ± 0.66 mm, p = .91) or its thickness (1.28 ± 0.44 and 1.40 ± 0.78 mm, p = .87). Apically positioned flap combined with a collagen matrix results in a more apical position of the MGJ at sites with or without GBR. Following a coronal shift during the first month after the apical positioning of the flap, the level of the MGJ remained stable.


Characterization of B-cell non-Hodgkin's lymphomas. A study using a panel of monoclonal and heterologous antibodies.
A panel of monoclonal and heterologous antibodies directed against clearly defined antigens was used to characterize the cellular composition of 57 non-Hodgkin's lymphomas, classified according to the Kiel classification, with a slight modification. The antisera were directed against T-lymphocytes and their subsets (Leu1, Leu2a, Leu3a, TA1), B-lymphocytes and their subsets (BA1, BA2, HLA-DR, CR1, sIg), macrophages (TA1, OKM1, anti-human monocyte 1, HLA-DR, CR1), dendritic reticulum cells (CR1, BA2, HLA-DR), interdigitating reticulum cells (HLA-DR, BA1) and Langerhans cells (OKT6, NA1/34). On the basis of the staining pattern of the neoplastic cells with the antibodies used and the nature and number of admixed cells, in particular T-cell subsets, dendritic reticulum cells and macrophages, the NHL could be divided into groups which correspond to the different diagnostic categories of the Kiel classification. Furthermore, the results underlined the existence of intermediate lymphocytic lymphoma as a separate diagnostic category. Histogenetically, the marker pattern of the neoplastic cells and the number and arrangement of the admixed cells are consistent with the view that at least two different lines of B-cell lymphomas can be recognized. One is related to the germinal centre cell reaction (to which B-lymphoblastic (Burkitt type), centroblastic, centroblastic/centrocytic, centrocytic, and intermediate lymphocytic lymphoma, and polymorphic immunocytoma belong) and the other is related to the plasma cell reaction (including chronic lymphocytic leucaemia and lymphoplasmacytoid immunocytoma), whereas B-immunoblastic lymphoma can originate from either line. Thus, polymorphic immunocytoma is a follicle centre cell lymphoma with differentiation into plasma cells rather than a lymphoplasmacytoid immunocytoma with blastic cells.


Antibiotic Consumption and Stewardship at a Hospital outside of an Early Coronavirus Disease 2019 Epicenter.
There are scant data on the impact of coronavirus disease 2019 (COVID-19) on hospital antibiotic consumption, and no data from outside epicenters. At our nonepicenter hospital, antibiotic days of therapy (DOT) and bed days of care (BDOC) were reduced by 151.5/month and 285/month, respectively, for March to June 2020 compared to 2018-2019 (P = 0.001 and P < 0.001). DOT per 1,000 BDOC was increased (8.1/month; P = 0.001). COVID-19 will impact antibiotic consumption, stewardship, and resistance in ways that will likely differ temporally and by region.


Umbilical cord management - the first opportunity to improve healthcare disparities.
This review focuses on iron deficiency and iron deficiency anemia in women and children in the United States. These are common, fixable problems that disproportionally affect minority populations. There are many opportunities for successful screening and management. The knowledge and awareness for identification and treatment of our populations' commonest deficiency is crucial.


Rituximab in the treatment of refractory autoimmune cytopenias in adults.
We report the results of four cycles of rituximab therapy in eleven patients with chronic warm antibody type autoimmune hemolytic anemia (AIHA) and six patients with chronic idiopathic thrombocytopenia (ITP). The overall response rate was 64% in the AIHA group (3 complete responses and 4 partial responses) and 83% in the ITP group (4 complete responses, 1 partial response). Responses in AIHA patients with underlying lymphoproliferative disorders receiving rituximab with chemotherapy were generally better sustained, whereas responses in ITP were often transient.


Statin therapy after acute myocardial infarction: are we adequately treating high-risk patients?
After acute myocardial infarction, patients remain at high risk for recurrent cardiovascular events and mortality. Despite the compelling scientific and clinical trial evidence that lipid-lowering medications reduce mortality in patients after acute myocardial infarction, this life-saving therapy continues to be underutilized. A number of studies in a variety of clinical settings have documented that a significant proportion of patients after myocardial infarction are not receiving treatment with lipid-lowering medications when guided by conventional care. It has recently been demonstrated that implementation of a hospital-based system for initiation of statins prior to hospital discharge results in a marked increase in treatment rates, improved long-term patient compliance, more patients reaching low-density lipoprotein levels of less than 100 mg/dL, and improved clinical outcomes. Adopting in-hospital initiation of lipid-lowering medications as the standard of care for patients hospitalized with acute myocardial infarction could dramatically improve treatment rates and thus substantially reduce the risk of future coronary events and prolong life in the large number of patients hospitalized each year.


[STEMI network Essen-in-hospital results].
The myocardial infarction network "Herzinfarktverbund Essen", existing since 2004, was designed to introduce guideline therapy of ST elevation myocardial infarction (STEMI) into everyday clinical practice using primary percutaneous coronary intervention (PCI) as the preferred reperfusion strategy, early prescribing recommended medication and optimizing patient's pathway from the first symptom to rehabilitation in a city of 580,000 inhabitants. In the 1st year, 489 patients were treated in five high-volume PCI centers. 444 primary PCIs were performed (90.8%). In-hospital mortality was 7.6% and thus lower than in other, historical STEMI registers with similar baseline characteristics but lower PCI rate. The best risk predictor was left ventricular function. Patients with an ejection fraction (EF) <or= 30% had a 27 times higher mortality risk than those with normal EF. Guideline-recommended medication was prescribed in 75% of patients (acetylsalicylic acid [ASS], clopidogrel, beta-blockers, and statins) and in 71%, respectively, with additional ACE inhibitor (five drugs). 72% of these patients were referred to rehabilitation therapy. The "Herzinfarktverbund Essen" demonstrates, that implementing guideline-conformal therapy into an urban area may result in a lower in-hospital mortality, a higher rate of patients prescribed recommended medication and a stronger patient adherence to ambulant therapy.


Fragment synthesis of disulfide-containing peptides.
A new strategy for solid phase peptide synthesis in the fragment synthesis based on the use of 2-Cl-trityl resin as carrier to obtain protected peptide-resin and Rink Amide Resin, HOBT/HBTU or PyBOP/DIPEA or HATU/DIPEA as the coupling method is described. The highlights of this method are:•Simple.•Low cost.•Solid phase based.


Surface integration approach: a new technique for evaluating geometry dependent forces between objects of various geometry and a plate.
We present a new approach, which can be considered as a generalization of the Derjaguin approximation, that provides exact means to determine the force acting between a three-dimensional body of any shape and a half-space mutually interacting via pairwise potentials. Using it, in the cases of the Lennard-Jones, standard and the retarded (Casimir) van der Waals interactions we derive exact expressions for the forces between a half-space or a slab of finite thickness and an ellipsoid in a general orientation, which in the simplest case reduces to a sphere, a tilted fully elliptic torus, and a body obtained via rotation of a single loop generalized Cassini oval, a particular example of which mimics the shape of a red blood cell. The results are obtained for the case when the object is separated from the plane via a non-polar continuous medium that can be gas, liquid or vacuum. Specific examples of biological objects of various shapes interacting with a plate like substrates are also considered.


ZIF-67-derived Co/CoSe ultrafine nanocrystal Schottky heterojunction decorated hollow carbon nanospheres as new-type anodes for potassium-ion batteries.
Metal-organic frameworks (MOFs) have the advantages of controllable chemical properties, rich pore structures and reaction sites and are expected to be high-performance anode materials for the next generation of potassium-ion batteries (PIBs). However, due to the large radius of potassium ions, the pure MOF crystal structure is prone to collapse during ion insertion and processing, so its electrochemical performance is quite limited. In this work, a hollow carbon sphere-supported MOF-derived Co/CoSe heterojunction anode material for potassium-ion batteries was developed by a hydrothermal method. The anode has high potassium storage capacity (461.9 mA h/g after 200 cycles at 1 A/g), excellent cycling stability and superior rate performance. It is worth noting that the potassium ion storage capacity of the anode material shows a gradual upward trend with the charge-discharge cycle, which is 145.9 mA h/g after 3000 cycles at a current density of 10 A/g. This work demonstrates that MOF-derived CoSe anodes with high capacity and low cost may be promising candidates for the introduction of potassium ion storage.


Sodium caseinate hinders chymosin-induced aggregation of caseins in concentrated milk: The role of soluble caseins and calcium ions.
Concentrated casein micelle suspensions show an altered balance between the colloidal and soluble phases compared with native skim milk. The objective of this research was to probe the role of such a change on the chymosin-driven destabilization of casein micelles. Skim milk was gently concentrated by osmotic stressing to increase the volume fraction of the micelles while maintaining a constant ionic composition. In situ turbidity measurements demonstrated that the secondary stage of gelation was hindered in the concentrated suspensions. Addition of ionic calcium overcame this inhibition, whereas restoring the original concentration by redilution did not. This work clearly demonstrated that calcium plays a major role in decreasing electrostatic repulsion in casein micelles, but also showed the importance of noncolloidal proteins in altering the gelling functionality of casein micelles in concentrated milk. Additional calcium induces aggregation of these soluble caseins, restoring gelation in concentrates.


Estrous cycle stage-dependent expression of acute tolerance to morphine analgesia in rats.
Both baseline pain sensitivity and the response to antinociceptive treatment are sensitive to an animal's sex and estrous cycle stage. Sex differences are also observed in the development of antinociceptive tolerance induced by repetitive exposure to opiate drugs such as morphine. Conventional tolerance study protocols do not assess the impact of the estrous cycle stage. The present study aimed to compare the development of acute tolerance to morphine-induced antinociception in male and female (cycling and ovariectomized) Wistar rats using the tail-flick test. Acute tolerance was induced by two consecutive subcutaneous injections of morphine (10 mg/kg) or saline separated by an interval of 6 h. It was found that rats pretreated with morphine were tolerant to the second morphine dose. Tolerance was most pronounced in proestrous female rats and, to a lesser degree, in male rats. It was absent in ovariectomized rats as well as during the estrus, metestrus and diestrus phases. Thus, the estrous cycle exerts dramatic effects on the induction of acute tolerance to morphine-induced antinociception. These results suggest that pain management strategies can be optimized through the use of sex- and estrous cycle-specific techniques.


New iridium complexes with cyclometalated 2-arylimidazole ligands as highly efficient saturated green emitters.
Phosphorescence studies of a series of heteroleptic cyclometalated iridium(III) complexes have been carried out. From the photoluminescent properties, it was found that these complexes possess dominantly (3)MLCT and (3)π-π* excited states. The solvent shifts are interpreted in terms of Reichardt-Dimroth solvent E(T) parameters and Marcus theory. The results are consistent with prior assignments on the absorption band to a metal-to-ligand charge transfer excited state associated with chelating ligand. Emission kinetic studies reveal that k(r) increases with increasing λ(em) and linear correlation between ln(k(nr)) and energy gap. The effect of E(g) and ΔQ(e) on k(nr) is discussed in detail.


Solution by dilution?--A review on the pollution status of the Yangtze River.
The Yangtze River has been a source of life and prosperity for the Chinese people for centuries and is a habitat for a remarkable variety of aquatic species. But the river suffers from huge amounts of urban sewage, agricultural effluents, and industrial wastewater as well as ship navigation wastes along its course. With respect to the vast amounts of water and sediments discharged by the Yangtze River, it is reasonable to ask whether the pollution problem may be solved by simple dilution. This article reviews the past two decades of published research on organic pollutants in the Yangtze River and several adjacent water bodies connected to the main stream, according to a holistic approach. Organic pollutant levels and potential effects of water and sediments on wildlife and humans, measured in vitro, in vivo, and in situ, were critically reviewed. The contamination with organic pollutants, including polycyclic aromatic hydrocarbons, polychlorinated biphenyls (PCBs), organochlorine pesticides (OCPs), polychlorinated dibenzo-p-dioxins/polychlorinated dibenzofurans, polybrominated diphenyl ethers (PBDEs), perfluorinated compounds (PFCs), and others, of water and sediment along the river was described. Especially Wuhan section and the Yangtze Estuary exhibited stronger pollution than other sections. Bioassays, displaying predominantly the endpoints mutagenicity and endocrine disruption, applied at sediments, drinking water, and surface water indicated a potential health risk in several areas. Aquatic organisms exhibited detectable concentrations of toxic compounds like PCBs, OCPs, PBDEs, and PFCs. Genotoxic effects could also be assessed in situ in fish. To summarize, it can be stated that dilution reduces the ecotoxicological risk in the Yangtze River, but does not eliminate it. Keeping in mind an approximately 14 times greater water discharge compared to the major European river Rhine, the absolute pollution mass transfer of the Yangtze River is of severe concern for the environmental quality of its estuary and the East China Sea. Based on the review, further research needs have been identified.


Safety and efficacy of intraoperative intravitreal injection of triamcinolone acetonide injection after phacoemulsification in cases of uveitic cataract.
To evaluate the safety and efficacy of a single intraoperative intravitreal injection of triamcinolone acetonide after phacoemulsification in patients with chronic idiopathic anterior uveitis or intermediate uveitis. Dr. R.P. Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India. This prospective randomized controlled study included 40 eyes (40 patients) with chronic idiopathic anterior uveitis or intermediate uveitis that had phacoemulsification with intraocular lens implantation. Twenty eyes received an intravitreal injection of triamcinolone acetonide (4 mg/0.1 mL) intraoperatively (triamcinolone acetonide group), and 20 received oral steroids (steroid group) postoperatively. Outcome measures were Early Treatment Diabetic Retinopathy Study best corrected visual acuity (BCVA), anterior chamber reaction, intraocular pressure (IOP) by applanation tonometry, and central macular thickness by optical coherence tomography. The mean BCVA (decimal) improved from a baseline of 0.13 +/- 0.14 to 0.64 +/- 0.32 in the triamcinolone acetonide group and from 0.05 +/- 0.06 to 0.61 +/- 0.36 in the steroid group (P = .74). There were no statistically significant differences between the 2 groups in postoperative anterior chamber reaction, IOP, or central macular thickness. Four patients in the triamcinolone acetonide group and 5 in the steroid group had recurrence of uveitis; 5 patients in the triamcinolone acetonide group had ocular hypertension. One patient in the triamcinolone acetonide group and 3 in the steroid group had cystoid macular edema postoperatively. A single intraoperative intravitreal injection of triamcinolone acetonide seemed to be a safe and efficacious route of steroid delivery during phacoemulsification in patients with chronic idiopathic anterior uveitis or intermediate uveitis and is recommended as a substitute for postoperative oral steroid administration.


Excessive Copper(II) and Zinc(II) Levels in Drinkable Water Sources in Areas Along the Lake Victoria Shorelines in Siaya County, Kenya.
Copper(II) and zinc(II) levels in drinkable water sources in the alluvium areas of the Lake Victoria Basin in Siaya County of Kenya were evaluated to assess the risk posed to resident communities by hydrogeological accumulation of toxic residues in the sedimentary regions of the lake basin. The levels of the metals in water were analyzed by atomic absorption spectroscopy. Metal concentrations ranged from 0.11 to 4.29 mg/L for Cu(II) and 0.03 to 1.62 mg/L for Zn(II), which were both higher than those normally recorded in natural waters. The Cu(II) levels also exceeded WHO guidelines for drinking water in 27% of the samples. The highest prevalence of excessive Cu(II) was found among dams and open pans (38%), piped water (33%) and spring water (25%). It was estimated that 18.2% of the resident communities in the current study area are exposed to potentially toxic levels of Cu(II) through their drinking water.


QCM sensor provides insight into the role of pivotal ions in cellular regulatory volume decrease.
All vertebrate cells generally self-regulate for sustaining homeostasis and cell functions. As a major regulatory mechanism, regulatory volume decrease (RVD) occurs in hypotonicity-induced cell swelling, and then shrinking by the efflux of intracellular osmolytes and water, in which the ions K+, Cl-, and Ca2+ play a key role in the RVD process. We observed that these pivotal ions could result in novel RVD behaviors under repeatedly hypotonic stimulation. However, there is a lack of valid means for assessing the effect of pivotal ions on RVD. In this work, we proposed an effective measurement process based on a quartz crystal microbalance (QCM) combined with cell function of RVD for revealing acute variations in cell volume regulation induced by the pivotal ions. A QCM sensor was implemented by adhering MCF-7 cells to a poly-l-lysine-modified gold chip and cyclic stimulation with hypotonic NaCl medium, in which a frequency shift (Δf) showed the superior feasibility of the technique in exhibiting RVD behaviors. With the increase in the number of cycles, the RVD values decreased progressively under three stimulation cycles with hypotonic NaCl alone. Compared with the first cycle, the RVD level in the second and third cycles declined by 60.7±1.7% and 82.1±1.6% (n=3), respectively; conversely, it recovered in NaCl-KCl solution, but was significantly enhanced by 52.2±0.8% in NaCl-CaCl2 solution. Moreover, the inhibition of chloride channels to block Cl- efflux also decreased the RVD level by 56.2±3.0%. The results indicate that these ions (K+, Cl-, Ca2+) are all able to affect the function of RVD, among which intracellular Cl- depletion reduced RVD during measurement, but which recovered with K+ supplement, and Ca2+ enhanced RVD due to activation of ion channels. Therefore, this work provides a comprehensive assessment of cellular behavior and offers an innovative method for gaining insight into cellular functions and mechanisms. A novel strategy was conducted by integrating a quartz crystal microbalance (QCM) with the function of cell volume regulation for analyzing the role of the pivotal ions ( K+, Cl-, Ca2+) in NaCl media on the behaviors of regulatory cell volume decrease (RVD).


[Coronavirus and "astrovirus" observed in stools of children with gastroenteritis (author's transl)].
In a year's survey (December 1976-November 1977) of 190 children admitted to hospital with acute gastroenteritis, an "aetiological" agent was found in stools by electron microscopy in 41% of cases. Rotavirus were found in 34% of patients. We also found Coronavirus-like particles and Astrovirus-like particles in 25 and 5 stools, respectively. Improvements are awaited to demonstrate the responsibility of these virus in gastroenteritis.


A Pragmatic Pilot Cluster-Randomized Study of Tobacco Screening and Smoking Cessation Program for Community Pharmacies in Japan: FINE Program.
To investigate the effectiveness of a smoking cessation program (FINE program) in community pharmacies. A cluster-randomized controlled trial was conducted in 11 community pharmacies in Japan. The participants were randomly assigned to a pharmacist-led structured smoking cessation program (intervention group) or pharmacist-led usual care (control group). The intervention group was followed up over the telephone on the third day of smoking cessation, and ongoing follow-up and advice were provided according to the original smoking cessation guidebook developed for the current study based on a behavioral change approach. The control group received brief advice and ready-made pamphlets on smoking cessation from pharmacists upon their visit to these community pharmacies. The primary outcome was continued smoking cessation as determined by self-reporting and carbon monoxide monitoring with a microsmokerlyzer after 3 months. Five hundred and seventy-two smokers who met the eligibility criteria visited the pharmacies included in the study. Of these individuals, 24 patients agreed to participate in the study. The quit rates were 45.5% and 18.2% in the intervention and control groups, respectively (P = 0.380, effect size = 0.60). Based on the effect size values, the FINE program may be effective to some extent, but the difference was not significant. We speculate that this is related to the small sample size due to difficulty in recruiting. Further studies with an effective recruitment method and larger sample sizes are needed to accurately verify the effectiveness of this program.


[C-peptide: secretion and metabolism in different functional states and with abnormal B-cell function (author's transl)].
Fasting C-peptide levels and those after tolbutamide or glucose stimulation were measured in normal subjects. In patients with various hypo- or hyper-functions of the endocrine pancreas, C-peptide levels were compared with the corresponding insulin levels. In insulin-dependent maturity-onset diabetics there were both normal and elevated serum C-peptide levels. In juvenile diabetics and patients with total duodenopancreatectomy there was no measureable C-peptide. It is concluded that the half-life of C-peptide is three times that of insulin.


N-(3-aminopropyl)pyrrolidin-2-one: a physiological excretory product deriving from spermidine.
Normal human and rat urine contain N-(3-aminopropyl)pyrrolidin-2-one. This compound was identified by its chromatographic behaviour on a reversed phase column, by thin-layer chromatography of its dansyl derivative, and by mass spectrometry. Evidence for the presence of conjugates of N-(3-aminopropyl)pyrrolidin-2-one in urine was obtained by the fact that partial acid hydrolysis increases the amount of this compound, whereas prolonged hydrolysis leads to its transformation into isoputreanine (N1-(3-carboxypropyl)-1,3-diamino-propane). Although it is likely that the monoacetylderivative of N-(3-aminopropyl)pyrrolidin-2-one is prominent among the conjugates, since this compound can be formed from N1-acetylspermidine, other types of conjugates are also likely. A method is reported suitable for the measurement of N-(3-aminopropyl)pyrrolidin-2-one and of isoputreanine in urine and urine hydrolysates, respectively. Administration of spermidine enhances the amount of urinary excretion of N-(3-aminopropyl)pyrrolidin-2-one. Of 0.1 mmol . kg-1 of spermidine administered intraperitoneally to rats around 12% are transformed into this compound and its conjugates. Treatment of rats with aminoguanidine sulfate, an inhibitor of diamine oxidase, causes a decrease in the excretion of N-(3-aminopropyl)pyrrolidin-2-one and its derivatives. These findings are in agreement with the assumption that N-(3-aminopropyl)pyrrolidin-2-one, the gamma-lactam of isoputreanine, is a physiological degradation product of spermidine. Its formation is catalyzed by an aminoguanidine sensitive, diamine oxidase-like enzyme.


Environmental performance measurement in arts and cultural organisations: Exploring factors influencing organisational changes.
Arts and Cultural Organisations (ACOs) have received significant attention over the last few years regarding their environmental performance. ACOs are often non-profit organisations, relying on government funding to implement various programmes to support societal development. Funding dependence can shift ACOs' focus from creating socio-cultural value to being more commercially driven. This paper explores factors influencing organisational changes in ACOs related to environmental performance measurement. Stakeholders in ACOs based in Nottingham, England, were interviewed and participated in a workshop to validate and collect additional data. Our research uncovered five interrelated factors that influence organisational change: the role of funding bodies; local policies and networks; organisational culture and leadership; lack of resources; and building proprietary-tenant relationships. This paper contributes to understanding ACOs responses to measuring environmental performance and the challenges they face as they move from measuring to implementation. Implications are explored for how funding is allocated and understood in terms of moving beyond merely measuring the carbon footprint of activities. ACOs' funding dependence indicates a focus on carbon measurement, omitting a more holistic approach towards the environment and sustainability.


Update on Antiseizure Medications 2022.
The article "Update on Antiseizure Medications 2022" by Dr Abou-Khalil was first published in the February 2016 Epilepsy issue of Continuum: Lifelong Learning in Neurology as "Antiepileptic Drugs," and at the request of the Editor-in-Chief was updated by Dr Abou-Khalil for the 2019 issue and again for this issue.


Highly pathogenic avian influenza (H5N1) outbreaks in wild birds and poultry, South Korea.
Highly pathogenic avian influenza (H5N1) among wild birds emerged simultaneously with outbreaks in domestic poultry in South Korea during November 2010-May 2011. Phylogenetic analysis showed that these viruses belonged to clade 2.3.2, as did viruses found in Mongolia, the People's Republic of China, and Russia in 2009 and 2010.


Relation of microalbuminuria to adiponectin and augmented C-reactive protein levels in men with essential hypertension.
Microalbuminuria, and recently, hypoadiponectinemia, have been associated with progression of atherosclerotic disease and increased cardiovascular risk. We examined the possible associations of urinary albumin excretion, expressed as the ratio of albumin to creatinine (ACR), with plasma adiponectin and high-sensitivity C-reactive protein (hs-CRP) levels in men who had essential hypertension. The study population consisted of 108 men who did not have diabetes and were newly diagnosed with stage I to II essential hypertension (age 44.6 years, office blood pressure 148/95 mm Hg) and 110 men matched according to age and body mass index as controls. According to ACR values, which were determined as the average of 2 nonconsecutive overnight spot urine samples, subjects who had hypertension were categorized into 2 groups: those who had microalbuminuria (n = 28; mean ACR 30 to 300 mg/g) and those who had normal albuminuria (n = 80; mean ACR <30 mg/g). Subjects who had hypertension compared with controls exhibited higher ACR and log hs-CRP levels and a trend toward lower log adiponectin values (p = 0.062), whereas those who had normal albuminuria compared with controls had similar log adiponectin levels but significantly higher levels of ACR and log hs-CRP. Moreover, subjects who had hypertension and microalbuminuria compared with those who had hypertension and normal albuminuria had higher log hs-CRP and lower log adiponectin concentrations independently of confounding factors. Among those who had hypertension, ACR exhibited an independent positive correlation with log hs-CRP and a negative correlation with log adiponectin. Multiple linear regression analysis showed that age, body mass index, systolic blood pressure, log hs-CRP, and log adiponectin were significant independent predictors of the ACR. In conclusion, microalbuminuria is accompanied by decreased adiponectin and increased hs-CRP levels in the setting of essential hypertension, reflecting a rather diffuse atherosclerotic process.


Risk of high blood pressure in salt workers working near salt milling plants: a cross-sectional and interventional study.
Workers working close to salt milling plants may inhale salt particles floating in the air, leading to a rise in plasma sodium, which, in turn, may increase the blood pressure and the risk of hypertension. To test the above hypothesis, occupational health check-up camps were organized near salt manufacturing units and all workers were invited for a free health examination. The workers who worked with dry salt in the vicinity of salt milling plants were defined as "non-brine workers," while those working in brine pans located far away from milling plants were defined as "brine workers." Blood pressure (BP) was measured during each clinical examination. In all, 474 non-brine workers and 284 brine workers were studied. Mean systolic blood pressure of non-brine workers (122.1 +/- 13.3 mm Hg) was significantly higher than that of brine workers (118.8 +/- 12.8 mm Hg, p < 0.01). Mean diastolic blood pressure of non-brine workers (71.5 +/- 10.4 mm Hg) was significantly higher than that of brine workers (69.7 +/- 9.4 mm Hg, p = 0.02). The prevalence of hypertension was significantly higher in non-brine workers (12.2%) than in brine workers (7.0%, p = 0.02). Nineteen salt workers were monitored while they used face masks and spectacles, for six days. Systolic, as well as diastolic, blood pressure of these workers began declining on the third day and continued to decline on the fourth day, but remained stationary up to the sixth day. The concentration of salt particles in the breathing zone of these workers was 376 mg/m3 air. Inhalation of salt particles in non-brine workers may be an occupational cause of increased blood pressure.


Inverse relationship between onset and duration of EEG effects of six peripherally administered peptides.
Electrical activity in the rat brain after the peripheral injection of equimolar (0.1 mM) doses of Metenkephalin, Leu-enkephalin, beta-endorphin, gamma-endorphin, DSIP, and alpha-MSH was assessed by power spectral analysis. The mean onset of EEG activity for each peptide varied between 13.7 and 20.7 minutes and lasted between 27.8 and 40.8 minutes. The significant (p less than 0.001) interaction between duration and latency revealed that the longer the latency, the shorter the duration. Similar findings were observed after injection of the same peptides at a fixed dose of 80 microgram/kg body weight. Thus, the results demonstrate that peripherally injected peptides can exert EEG effects that last longer the sooner they start.


Roles for mycobacterial DinB2 in frameshift and substitution mutagenesis.
Translesion synthesis by translesion polymerases is a conserved mechanism of DNA damage tolerance. In bacteria, DinB enzymes are the widely distributed promutagenic translesion polymerases. The role of DinBs in mycobacterial mutagenesis was unclear until recent studies revealed a role for mycobacterial DinB1 in substitution and frameshift mutagenesis, overlapping with that of translesion polymerase DnaE2. Mycobacterium smegmatis encodes two additional DinBs (DinB2 and DinB3) and Mycobacterium tuberculosis encodes DinB2, but the roles of these polymerases in mycobacterial damage tolerance and mutagenesis is unknown. The biochemical properties of DinB2, including facile utilization of ribonucleotides and 8-oxo-guanine, suggest that DinB2 could be a promutagenic polymerase. Here, we examine the effects of DinB2 and DinB3 overexpression in mycobacterial cells. We demonstrate that DinB2 can drive diverse substitution mutations conferring antibiotic resistance. DinB2 induces frameshift mutations in homopolymeric sequences, both in vitro and in vivo. DinB2 switches from less to more mutagenic in the presence of manganese in vitro. This study indicates that DinB2 may contribute to mycobacterial mutagenesis and antibiotic resistance acquisition in combination with DinB1 and DnaE2.


The role of objective measurement of skeletal muscle function in the pre-operative patient.
The clinical value of objective measurement of skeletal muscle function was studied in 37 pre-operative patients with carcinoma of the gastrointestinal tract. Muscle function was determined in the adductor pollicis muscle of the thumb after stimulation of the ulnar nerve at the wrist. There was a difference in the force-frequency relationship (F10/F100) between patients with a recalled weight loss of 5 kg or more in the 3 months prior to admission compared to those who had not lost weight. Muscle function was normalized by 7 days of pre-operative intravenous nutrition. Pre-operative measurement of skeletal muscle function enabled identification of patients who subsequently developed a post-operative complication with a specificity of 89%, sensitivity of 39% and predictive index of 78%. Objective measurements of skeletal muscle function are of potential value for the prediction of post-operative complications, and may help to define patients who need nutritional support.


Prevalence and patterns of multimorbidity among tuberculosis patients in Brazil: a cross-sectional study.
The number of subjects with tuberculosis (TB) presenting with co-occurrence of multiple chronic medical conditions, or multimorbidity (MM) is increasing in Brazil. This manuscript aimed to characterize subjects with TB, according to their MM status and to analyse factors associated with TB treatment outcomes. This is a cross-sectional study that included 39,881 TB subjects reported in Brazil, in 2011. MM were defined as any (two or more) occurrence of chronic medical conditions in a TB patient (TB-MM). Data analysis was performed by hierarchical logistic regression models comparing TBMM with those with only TB. Of the reported TB cases in 2011, 454 (1.14%) had MM. The subjects in the age group 40-59 years (OR: 17.89; 95% CI, 5.71-56.03) and those ≥ 60 years (OR: 44.11; 95% CI, 14.09-138.06) were more likely to develop TB-MM. The TB-MM subjects were less likely to be male (OR: 0.63; 95% CI, 0.52-0.76), institutionalized (OR: 0.59; 95% CI, 0.23-0.80) and live in rural areas (OR: 0.63; 95% CI, 0.42-0.95). Death from causes other than TB was higher among TB-MM subjects (OR: 1.76; 95% CI, 1.36-2.28). Of 454 TB-MM subjects 302 (66.5%) were cured and 152 (33.5%) were not cured. The odds of not being cured was 1.55 (95% CI, 1.04-2.32) among males, 2.85 (95% CI, 1.12-7.28) among institutionalized subjects, and 3.93 (IC 95%, 1.86-8.30) among those who were infected with HIV. TB retreatment after previous abandonment (OR: 7.53; 95% CI, 2.58-21.97) and transfer from a treatment site (OR: 2.76; 95% CI, 1.20-6.38) were higher for subjects not cured compared to those who were cured. While TB is well recognized to be a disease engendered by social inequity, we found that even among TB patients, those who have MM have greater inequity in terms of socioeconomic status and adverse clinical outcomes. Addressing the problem of TB and TB-MM requires a multisectorial approach that includes health and social service organizations.


Epidemiology and Natural History of Elderly-onset Inflammatory Bowel Disease: Results From a Territory-wide Hong Kong IBD Registry.
Elderly-onset inflammatory bowel disease [IBD], defined as age ≥60 at diagnosis, is increasing worldwide. We aimed to compare clinical characteristics and natural history of elderly-onset IBD patients with those of adult-onset IBD patients. Patients with a confirmed diagnosis of IBD from 1981 to 2016 were identified from a territory-wide Hong Kong IBD registry involving 13 hospitals. Demographics, comorbidities, clinical features, and outcomes of elderly-onset IBD patients were compared with those of adult-onset IBD patients. A total of 2413 patients were identified, of whom 270 [11.2%] had elderly-onset IBD. Median follow-up duration was 111 months (interquartile range [IQR]: 68-165 months). Ratio of ulcerative colitis [UC]: Crohn's disease [CD] was higher in elderly-onset IBD than in adult-onset IBD patients [3.82:1 vs 1.39:1; p <0.001]. Elderly-onset CD had less perianal involvement [5.4% vs 25.4%; p <0.001] than adult-onset CD. Elderly-onset IBD patients had significantly lower cumulative use of immunomodulators [p = 0.001] and biologics [p = 0.04]. Elderly-onset IBD was associated with higher risks of: cytomegalovirus colitis (odds ratio [OR]: 3.07; 95% confidence interval [CI] 1.92-4.89; p <0.001); herpes zoster [OR: 2.42; 95% CI 1.22-4.80; p = 0.12]; and all cancer development [hazard ratio: 2.97; 95% CI 1.84-4.79; p <0.001]. They also had increased number of overall hospitalisations [OR: 1.14; 95% CI 1.09-1.20; p <0.001], infections-related hospitalisation [OR: 1.87; 95% CI 1.47-2.38; p <0.001], and IBD-related hospitalisation [OR: 1.09; 95% CI 1.04- 1.15; p = 0.001] compared with adult-onset IBD patients. Elderly-onset IBD was associated with increased risk of infections and cancer development, and increased infection- and IBD-related hospitalisations. Specific therapeutic strategies to target this special population are needed.


Use of the cobas 4800 system for the rapid detection of toxigenic Clostridium difficile and methicillin-resistant Staphylococcus aureus.
The new cobas® Cdiff and cobas® MRSA/SA tests were compared with conventional methods for the rapid detection of toxigenic Clostridium difficile and methicillin-resistant Staphylococcus aureus. The final concordance between cobas Cdiff Test and GDH/toxin gene screening was 97.62% and between cobas MRSA/SA Test and chromogenic culture, 91.30%, respectively.


Frequency of major complications of aspirin, warfarin, and intravenous heparin for secondary stroke prevention. A population-based study.
Complication rates of medical therapy for secondary stroke prevention derived from clinical trials may or may not be applicable to patients with cerebrovascular disease in the general population. To determine complication rates for aspirin, warfarin, and intravenous heparin administered for secondary stroke prevention after first episodes of ischemic stroke, transient ischemic attack, or amaurosis fugax in a community. Population-based historical cohort study. Rochester, Minnesota. All residents of Rochester who, between 1985 and 1989, received aspirin (n = 339) or warfarin (n = 145) within 2 years after first ischemic stroke, transient ischemic attack, or amaurosis fugax or received intravenous heparin (n = 201) within 2 weeks after first ischemic stroke, transient ischemic attack, or amaurosis fugax. Occurrence of major complications caused by therapy. Twenty aspirin-associated complications (1 fatal) occurred during an average 1.7 years of treatment, 8 warfarin-associated complications occurred during an average 0.7 years of treatment, and 3 heparin-associated complications (1 fatal) occurred during an average 5.1 days of treatment. Complication rates were 3.5 per 100 person-years (95% CI, 2.1 to 5.4) for aspirin, 7.9 per 100 person-years (CI, 3.4 to 15.6) for warfarin, and 0.30 (CI, 0.06 to 0.86) per 100 person-days for heparin. Rates of fatal complications were 0.2 per 100 person-years (CI, 0 to 1.0) for aspirin, 0 per 100 person-years (CI, 0 to 3.6) for warfarin, and 0.10 per 100 person-days (0 to 0.55) for heparin. Complication rates for warfarin and intravenous heparin given as therapy for secondary stroke prevention in Rochester, Minnesota, were lower than rates reported from earlier trials and observational studies. However, complication rates for warfarin were higher than in more recent referral-based studies and multicenter randomized trials. After adjustment for duration of therapy, complication rates for heparin were higher than those for aspirin or warfarin. These rates can be used to judge the applicability of complication rates derived from ongoing clinical trials.


Plaque Imaging to Decide on Optimal Treatment: Medical Versus Carotid Endarterectomy Versus Carotid Artery Stenting.
Many of the current guidelines for the management of carotid atherosclerosis are based on clinical trial findings published more than 2 decades ago. The lack of plaque information in clinical decision making represents a major shortcoming and highlights the need for contemporary trials based on characteristics of the atherosclerotic lesion itself, rather than luminal stenosis alone. This article summarizes the major dilemmas clinicians face in current practice, and discusses the rationale and evidence that plaque imaging may help to address these challenges and optimize the clinical management of carotid artery disease in the future.


5-Bromo-2,7-dimethyl-3-(4-methyl-phenyl-sulfin-yl)-1-benzo-furan.
In the title compound, C17H15BrO2S, the 4-methyl-benzene ring makes a dihedral angle of 89.01 (7)° with the mean plane [r.m.s. deviation = 0.013 (2) Å] of the benzo-furan fragment. In the crystal, mol-ecules are linked into supra-molecular layers that stack along [001] by weak C-H⋯O, C-H⋯π and C-S⋯π [3.364 (2) Å] inter-actions.


[Dynamics of changes in morphometric parameters of the macular zone in glaucoma patients after phacoemulsification].
To analyze the dynamics of morphometric changes in the macular zone using optical coherence tomography (OCT) data in patients with primary open-angle glaucoma (POAG) after phacoemulsification (PE). The study enrolled 93 patients (95 eyes) requiring PE; they were divided into 2 groups. The first (control) group consisted of 30 patients (32 eyes) without concomitant eye pathology. The second group included 63 patients (64 eyes) with POAG and IOP stabilized by eye drops. In the 2A subgroup (32 eyes) patients used prostaglandin analogues, in the 2B subgroup (31 eye) - carbonic anhydrase inhibitors. OCT was used to analyze retinal thickness and volume. OCT was performed before PE, after 1 week, after 1, 3, and 6 months. In the control group, the volume and thickness of the retina varied within the normal range. In the 2A subgroup, signs of macular edema (ME) in the early post-operative period were noted in 6.2% of patients. In the late post-operative period, changes in the macular zone were noted in 18.7% of cases. After the treatment, ME regressed completely in 4 patients (12.5% of all cases). One patient with retinal thickness of more than 500 µm required parabulbar and intravenous injections of glucocorticoids, which resulted in ME decrease. Another patient developed epiretinal fibrosis with tractions after ME. Among the patients of subgroup 2B, a trend for increase in the volume and thickness of the macular zone was observed in 3 cases; the values stayed within the normal range, and later returned to the initial level. Patients with POAG develop ME after PE in 1-3 months. The use of topical prostaglandin analogues may be the reason of ME development.


Estimation of Primary Prevention of Gout in Men Through Modification of Obesity and Other Key Lifestyle Factors.
The population impact of modifying obesity and other key risk factors for hyperuricemia has been estimated in cross-sectional studies; however, the proportion of incident gout cases (a clinical end point) that could be prevented by modifying such factors has not been evaluated. To estimate the proportion of incident gout cases that could be avoided through simultaneous modification of obesity and other key risk factors. The Health Professionals Follow-up Study is a US prospective cohort study of 51 529 male health professionals enrolled in 1986 and followed up through questionnaires every 2 years through 2012. Self-reported gout cases were confirmed through June 2015. Clean and complete data used for this analysis were available in June 2016, with statistical analyses performed from July 2016 to July 2019. From data collected in the validated questionnaires, men were categorized to low-risk groups according to combinations of the following 4 factors: normal body mass index (BMI [calculated as weight in kilograms divided by height in meters squared]; <25), no alcohol intake, adherence to Dietary Approaches to Stop Hypertension (DASH)-style diet (highest quintile of DASH diet score), and no diuretic use. Population attributable risks (PARs) for incident gout meeting the preliminary American College of Rheumatology survey criteria, overall and stratified by BMI. We analyzed 44 654 men (mean [SD] age, 54.0 [9.8] years) with no history of gout at baseline. During 26 years of follow-up, 1741 (3.9%) developed incident gout. Among all participants, PAR for the 4 risk factors combined (BMI, diet, alcohol use, and diuretic use) was 77% (95% CI, 56%-88%). Among men with normal weight (BMI <25.0) and overweight (BMI 25.0-29.9), we estimated that more than half of incident gout cases (69% [95% CI, 42%-83%] and 59% [95% CI, 30%-75%], respectively) may have been prevented by the combination of DASH-style diet, no alcohol intake, and no diuretic use. However, among men with obesity (BMI ≥30), PAR was substantially lower and not significant (5% [95% CI, 0%-47%]). The findings of this cohort study suggest that addressing excess adiposity and other key modifiable factors has the potential to prevent the majority of incident gout cases among men. Men with obesity may not benefit from other modifications unless weight loss is addressed.


Peritoneal endometriosis. Report of a case with cytologic, cytochemical and histopathologic study.
The cytologic and histochemical data in a case of extensive peritoneal endometriosis are presented. The presence of macrophages heavily laden with blue and dark pigment (as demonstrated by May-Grünwald-Giemsa, Perls and Fontana stains) and scattered non-neoplastic endometrial cells in hemorrhagic ascitic fluid indicated a diagnosis of peritoneal endometriosis. Metabolized hemoglobin material was related to both recent and older hemorrhages.


Increased sensitivity to transient global ischemia in aging rat brain.
Transient global brain ischemia induced by cardiac arrest and resuscitation (CAR) results in reperfusion injury associated with oxidative stress. Oxidative stress is known to produce delayed selective neuronal cell loss and impairment of brainstem function, leading to post-resuscitation mortality. Levels of 4-hydroxy-2-nonenal (HNE) modified protein adducts, a marker of oxidative stress, was found to be elevated after CAR in rat brain. In this study we investigated the effects of an antioxidant, alpha-phenyl-tert-butyl-nitrone (PBN) on the recovery following CAR in the aged rat brain. Male Fischer 344 rats (6, 12 and 24-month old) underwent 7-minute cardiac arrest before resuscitation. Brainstem function was assessed by hypoxic ventilatory response (HVR) and HNE-adducts were measured by western blot analysis. Our data showed that in the 24-month old rats, overall survival rate, hippocampal CAl neuronal counts and HVR were significantly reduced compared to the younger rats. With PBN treatment, the recovery was improved in the aged rat brain, which was consistent with reduced HNE adducts in brain following CAR. Our data suggest that aged rats are more vulnerable to oxidative stress insult and treatment with PBN improves the outcome following reperfusion injury. The mechanism of action is most likely through the scavenging of reactive oxygen species resulting in reduced lipid peroxidation.


Situating Preventive Action in a Moral and Clinical Context: A Qualitative Synthesis on Fall Prevention.
The prevention of falls is an integral part of the safety culture of health institutions with mandatory fall prevention programs set within health care facilities. Care providers are key in identifying the risks of falls and in implementing strategic actions to prevent them. With the aim to better understand practices of fall prevention, we conducted a synthesis of qualitative evidence on care providers' practices to prevent older people from falling in health care facilities. This synthesis is part of an integrative review of the role of care providers in fall prevention of adults aged 65 years and above. Primary studies were synthesized with the emerging core category of "a complex decision" and described by four emerging conditions that make that decision complex: (a) permanent threat of a fall, (b) continuous flow of information, (c) lack of control, and (d) ethical dilemmas and moral issues over the course of action. The present synthesis shows that before implementing preventive actions, care providers consider the conditions in which they are immersed, in this way situating their preventive actions in a clinical and a moral context.


[Superselective arterial embolization for hemorrhage from malignant gestational trophoblastic tumor].
To evaluate the efficacy of superselective arterial embolization to control hemorrhage from malignant gestational trophoblastic tumor. From February 1990 to June 2001, 31 patients (choriocarcinoma 24, invasive mole 7) with hemorrhage from malignant gestational trophoblastic tumor were treated with superselective arterial embolization. The hemorrhage organs included uterus (22 cases), vagina (3 cases), liver (3 cases), bladder (2 cases), and intestine (1 case). In 28 cases (90.3%), superselective arterial embolization successfully controlled the hemorrhage. Hysterectomy was performed in the 3 failed and uterine perforation was revealed by laprotomy. Four patients had normal term delivery after successful superselective arterial embolization and chemotherapy. Superselective arterial embolization can effectively control the hemorrhage from malignant gestational trophoblastic tumor.


Development of novel method of non-viral efficient gene transfer into neonatal cardiac myocytes.
To establish new treatment for cardiovascular disease, the development of safe and highly efficient vectors is necessary. Especially, non-viral vectors are considered to be ideal for human gene therapy, since recent adverse events with retroviral or adenoviral vectors have highlighted the issue of safety. Although we previously reported safety and high efficiency of HVJ-liposome method, we have modified the envelope of HVJ (Sendai virus). In this novel non-viral vector, the envelope of HVJ alone was utilized as a carrier to deliver proteins, genes and oligodeoxynucleotides (ODN). Thus, we optimized the transfection efficiency of HVJ-envelope vector into neonatal cardiac myocytes in this study, since cardiac myocytes is one of the most difficult cells to be transfected. HVJ-envelope, obtained after complete destruction of HVJ genome, containing FITC-labeled ODN or luciferase plasmid was incubated with cardiac myocytes. In addition, the concentration of protamine sulfate was modified (0-700 microg/ml) to increase transfection efficacy. Without HVJ-envelope vector, few cells showed fluorescence, whereas most cells demonstrated fluorescence with HVJ-envelope vector. Consistent with the high transfection efficiency of ODN, high luciferase activity was also detected using HVJ-envelope vector. Moreover, the transfection efficiency varied according to the concentration of protamine sulfate. No obvious cytotoxicity was observed in cells transfected with HVJ-envelope vector. The present study demonstrated the development of a highly efficient novel non-viral vector for cardiac myocytes, suggesting that further development may provide a new useful tool for research and clinical gene therapy in the field of cardiovascular disease.


Caring for patients with limited English proficiency: the perspectives of small group practitioners.
Language barriers in medical care are a large and growing problem in the United States. Most research has focused on how language barriers affect patients. Less is known of the physician perspective and the efforts they are making to overcome these barriers. To learn about current approaches to communicating with limited English-proficient (LEP) patients and the associated financial and nonfinancial constraints that private practice physicians and managers perceive in providing these services. Computer-assisted telephone focus groups with open-ended discussion guide. Small private practices in geographic areas that have experienced recent dramatic increases in LEP populations. Primary care physicians, specialists, and practice managers. Focus group transcripts were systematically coded using grounded theory analysis. The research team then identified common themes that arose across the groups. Citing the cost, inaccessibility, and inconvenience of using professional interpreters, physicians commonly used family and friends as interpreters. Few recalled any actual experience with professional interpreters or were well-informed about the cost of their services. Physicians and office managers voiced uniform concern about how language barriers impede quality and safety of patient care and increased malpractice risk. Health care providers in private practice recognize the importance of overcoming language barriers. However, perceived barriers to implementing cost-effective strategies to these barriers are high. Physicians in private practice would benefit from information about how to best overcome language barriers in their practices efficiently and affordably.


Synaptic ribbons during postnatal development of the pineal gland in the golden hamster (Mesocricetus auratus).
Synaptic ribbons, functionally enigmatic structures of mammalian pinealocytes, were studied during the postnatal development of the pineal gland in the golden hamster (Mesocricetus auratus). On day 4 post partum, synaptic ribbons appear in cells that have already started to differentiate into pinealocytes. Between days 4 and 9, an increase in the number of synaptic ribbons occurs, concomitant with the continuing differentiation of the pineal tissue. Between days 9 and 16, when differentiation of this tissue is almost completed, the number of synaptic ribbons decreases and approaches that characteristic of the adult pineal gland. During development, the synaptic ribbons increase in length, and dense core vesicles are frequently found in the vicinity of these structures. It is assumed that a functional relationship exists between dense core vesicles and the synaptic ribbons, which are considered to be engaged in a certain form of secretory activity of the mammalian pineal gland.


Neuropeptide Y-Y2 receptors mediate anxiety in the amygdala.
The behavioral effects of direct injection of the neuropeptide Y (NPY) Y2 receptor agonist C2-NPY into the basolateral nucleus of the amygdala (BLA) was assessed in rats utilizing the social interaction test (SI). C2-NPY decreased SI time in a dose-dependent manner with a significant change observed at a dose of 80 pmol/100 nl. The anxiogenic effects produced by intra-amygdalar C2-NPY injections were reversed with intraperitoneal administration of alprazolam (1 mg/kg), a known anxiolytic. These findings support the hypothesis that Y2 receptors are involved in the regulation of the anxiety response.


Prospective evaluation of the relationship between platelet-leukocyte conjugate formation and recurrent myocardial ischemia in patients with acute coronary syndromes.
Platelet-leukocyte conjugates are increased in patients with coronary artery disease but the relationship between conjugate formation and myocardial ischemic outcome is unknown. We prospectively evaluated the relationship between conjugate formation and the development of recurrent myocardial ischemia in patients with acute coronary syndromes (ACS). Platelet-leukocyte conjugate formation (induced by thrombin receptor activating peptide (TRAP)) and platelet aggregation (induced by ADP and arachidonic acid) were assessed in 30 patients with unstable angina or non-ST elevation myocardial infarction. All patients were treated with beta-blockers, aspirin, heparin, and GPIIb-IIIa antagonists and were followed for in-hospital recurrent myocardial ischemia. Troponin I and C-reactive protein (CRP) were also measured. Seven patients (23%) experienced recurrent ischemia. Platelet-neutrophil conjugates were greater in ischemic patients (59 +/- 9 and 36 +/- 4%, P = 0.007, for + ischemia and -ischemia, respectively). Platelet aggregation did not differ between ischemic and nonischemic patients, and there was no significant relationship between aspirin resistance and ischemic outcome. Troponin I was greater in patients who developed recurrent ischemia (3.04 +/- 1.73 vs. 0.70 +/- 0.21 ng/ml, P = 0.03, for +ischemia and -ischemia, respectively) but CRP was not. TRAP-induced platelet-neutrophil conjugate formation was an independent predictor of ischemic outcome (OR 1.07, 95% CI 1.00-1.15, for each 1% increase in conjugate formation). Receiver operator characteristic analysis showed platelet-neutrophil conjugates to have good ability to discriminate between ischemic and nonischemic patients (AUC of 0.84, P < 0.05). TRAP induced platelet-neutrophil conjugate formation is related to in vivo ischemic risk in ACS patients.


Prognostic impact of pelvic and para-aortic lymphadenectomy on clinically-apparent stage I primary mucinous epithelial ovarian carcinoma: a multi-institutional study with propensity score-weighted analysis.
The exact impact of full-staging lymphadenectomy on patients with primary mucinous epithelial ovarian carcinoma confined to the ovary is still unclear. In this study, we investigated the prognostic impact of lymphadenectomy covering both pelvic and para-aortic lymph nodes in patients with clinically-apparent stage I mucinous epithelial ovarian carcinoma, using data from multi-institutions under a central pathological review system and analyses with a propensity score-based method. We conducted a regional multi-institutional retrospective study between 1986 and 2017. Among 4730 patients with malignant ovarian tumors, a total of 186 women with mucinous epithelial ovarian carcinoma were eligible. We evaluated differences in survival outcomes between patients with both pelvic and para-aortic lymphadenectomy and those with only pelvic lymphadenectomy and/or clinical lymph node evaluation. To analyze the therapeutic effects, the baseline imbalance between patients with both pelvic and para-aortic lymphadenectomy and others was adjusted with an inverse probability of treatment weighting using propensity score involving independent clinical variables. Fifty-five patients received both pelvic and para-aortic lymphadenectomy. With PS-based adjustment, both pelvic and para-aortic lymphadenectomy did not have additive effects regarding overall survival (P = 0.696) and recurrence-free survival (P = 0.978). Multivariate analysis similarly showed no significant impact of both pelvic and para-aortic lymphadenectomy on their prognosis. The effect of pelvic and para-aortic lymphadenectomy is limited for clinically-apparent stage I primary mucinous epithelial ovarian carcinoma as long as full peritoneal and clinical lymph node evaluations are conducted. The results of this study should be used as the basis for additional studies, including prospective trials.


Influence of cell disruption and elution on cellulase release of Clostridium straminisolvens (CSK1).
Clostridium straminisolvens (CSK1) is a novel cellulolytic bacterium isolated from a cellulose-degrading bacterial community MC1. In this study, the influence of the following cell disruption and elution methods on CSK1cellulase release was investigated: (1) freezing-thawing, (2) ultrasonication, (3) elution, (4) freezing-thawing following elution, (5) ultrasonication following elution, and lastly (6) high-pressure homogenization following elution. The activity of the cellulases CMCase, β-glucosidase, Avicelase, FPase, and xylanase in crude extracts increased 81.5, 23.8, 87.7, 46.3, and 51.7 %, respectively, with an observed optimal treatment method for each cellulase type. The release of protein from CSK1 cells increased following either cell disruption or elution and was highest at 88.3 % in the homogenization high pressure following elution treatment. A newly observed protein was present following cell elution. The performance of cell elution as determined by real time-PCR indicated that the first time cell elution removed more than 90 % of the CSK1 cells from the substrate. These findings demonstrate that cell disruption and elution are effective methods for inducing cellulase release, and elution is the key step for CSK1. To our knowledge, this study presents the first evidence of optimal treatments for induction of cellulase release of Clostridium straminisolvens. This information will be of great value for use in subsequent efforts to better understand the cellulase characteristics of CSK1 and cellulose degradation mechanisms of the MC1 community.


CHO cell growth and recombinant interferon-γ production: Effects of BSA, Pluronic and lipids.
The role of bovine serum albumin in mammalian cell cultures and the possibility of its substitution by other components in a serum-free medium has been investigated. In this study, BSA was shown to be important for growth and product formation in CHO cells expressing recombinant human interferon-γ. There were indications that its stimulating growth effect was dependent on the source of BSA used and probably was related to the purification procedure used for the production of the desired albumin fraction. Cell growth did not occur in the absence of BSA but at low concentration (1 mg ml(-1)) it was stimulated by the addition of a combination of a commercial lipid mixture plus Pluronic F68. However, under the latter conditions IFN-γ production was adversely effected. The importance of individual lipid components was investigated using a statistical approach based on a Plackett-Burman design. Linoleic acid was identified as a positive variable for cell growth while cholesterol was identified as a negative variable for both cell growth and IFN-γ production. When a combination of linoleic acid plus Pluronic F68 was included in the formulation of low BSA medium, cell growth was similar to that at high BSA concentration (5 mg ml(-1)) but the IFN-γ concentration was significantly reduced (ca. 45%).


Investigations of silane-MDP interaction in universal adhesives: A ToF-SIMS analysis.
The purposes of this study were to investigate whether the presence of silane in universal adhesives affects the functions of 10-methacryloyloxydecyl dihydrogen phosphate (MDP) and adhesion to zirconia. Two silane-containing universal adhesives (Scotchbond Universal (SBU) and Clearfil Universal-Bond (CUB)) and two silane-free adhesives (All-Bond Universal (ABU) and SE-Bond primer (SE)) were individually applied on zirconia disks. Time-of-flight secondary-ion-mass-spectrometry (ToF-SIMS) examined the distributions of MDP- and silane-related ions, as well as evidence of zirconium phosphate (ZrP) compounds, on the surface and interfacial regions using a depth profiling mode. The hydrophilicity and resin wettability of the treated zirconia were examined using a contact angle test. For the shear bond strength (SBS) test, the zirconia disks were air-blasted, treated with the assigned adhesives, and bonded with pre-cured composite cylinders using a resin cement. These resin-zirconia assemblies received a bond test after 24-h storage. Both SBU and CUB exhibited silane-related ions and ZrO2(OH)-, but fewer PO- ions in the interfacial regions. CUB had more siloxane-related ions. SE-treated zirconia had abundant PO- ions and particularly high PO3-- and ZrP- related ions in the interfacial regions. The silane-free adhesives exhibited a higher affinity to both water and adhesive liquids. SE showed significantly higher SBSs compared to ABU, while SBU and CUB were not statistically different. The silane content may cause hydroxylation of zirconia and affect MDP adsorption. An acidic pH accelerated the condensation of silanol. The bond performance of the MDP-based adhesive could be influenced by the silane content and other components.