Evaluation of [3H]paroxetine as an in vivo ligand for serotonin uptake sites: a quantitative autoradiographic study in the rat brain.
Paroxetine, a selective inhibitor of serotonin uptake and an antidepressant, was used in conjunction with quantitative ex vivo autoradiography to study the feasibility of imaging serotonin terminals in the living brain. Tritiated paroxetine was injected in the rat tail vein, and the brain was processed for quantitative autoradiography 3 hours later. Animals received either [3H]paroxetine alone (100 microCi/animal) or a mixture of labeled paroxetine (100 microCi) and an excess of unlabeled drug (0.5 or 2 mg/kg intravenously [i.v.]). Computerized image analysis of the resulting autoradiograms revealed high densities of radioactivity in brain regions known to contain high densities of serotonergic terminals and high specific binding of [3H] paroxetine in vitro, such as the raphe nuclei, interpeduncular nucleus, basolateral amygdala, substantia nigra, and some hypothalamic nuclei. Radioactivity uptake in these brain regions was effectively blocked (50-72%) by coadministration of excess unlabeled paroxetine. However, cortical and hippocampal binding of paroxetine in vivo was moderately high, in contrast to the relatively sparse serotonergic innervation in these regions. Only a relatively small proportion of cortical and hippocampal binding (20-40%) could be blocked by excess unlabeled paroxetine, indicating that most of the radioactivity in these regions is not associated with serotonin terminals or uptake sites. The usefulness of [3H]paroxetine as an in vivo ligand for imaging serotonin terminals in the human brain is limited by these nonserotonergic binding sites.


Regulation and effects of modulation of telomerase reverse transcriptase expression in primordial germ cells during development.
Telomere length maintenance in the germ line from generation to generation is essential for the perpetuation of eukaryotic organisms. This task is performed by a specialized reverse transcriptase called telomerase. While this critical function of telomerase has been well established, the mechanisms that regulate telomerase in the germ line are still poorly understood. We now show, using a Pou5f1-GFP transgenic mouse model, that telomerase suppression in quiescent male primordial germ cells (PGCs) is accompanied by a decrease in expression of murine telomerase reverse transcriptase (TERT). To further assess the role of TERT in quiescent PGCs, we developed a chicken Actb gene promoter/cytomegalovirus enhancer (CAG)-Tert transgenic mouse strain that constitutively expresses murine TERT. Telomerase activity was detected in quiescent PGCs from CAG-Tert transgenic embryos, demonstrating that re-activation of TERT expression is sufficient to restore telomerase activity in these cells and implying that TERT expression is an important mechanism of telomerase regulation in PGCs. Fluorescence-activated cell-sorting (FACS) analysis of PGC frequency and cell cycle status revealed no effect of either overexpression or deficiency of TERT in CAG-Tert transgenic mice or Tert knock-out mice respectively. These results demonstrate that TERT per se does not affect proliferation or development of PGCs, in contrast with recent studies that suggest that TERT has a telomere-independent effect in certain stem cells. It is possible that the direct effect of TERT on cell behavior may be dependent on cell type.


In adults with obesity, copeptin is linked with BMI but is not associated with long-term exposure to cortisol and cortisone.
Obesity and cardiometabolic diseases are associated with higher long-term glucocorticoid levels, measured as scalp hair cortisol (HairF) and cortisone (HairE). Cardiometabolic diseases have also been associated with copeptin, a stable surrogate marker for the arginine-vasopressin (AVP) system. Since AVP is, together with corticotropin-releasing hormone (CRH) an important regulator of the hypothalamic-pituitary adrenal axis (HPA axis), we hypothesize that AVP contributes to chronic hypercortisolism in obesity. To investigate whether copeptin levels are associated with Higher HairF and HairE levels in obesity. A cross-sectional study in 51 adults with obesity (BMI ≥30 kg/m2). Associations and interactions between copeptin, HairF, HairE, and cardiometabolic parameters were cross-sectionally analyzed. Copeptin was strongly associated with BMI and waist circumference (WC) (rho = 0.364 and 0.530, P = 0.008 and <0.001, respectively), also after correction for confounders. There were no associations between copeptin and HairF or HairE on a continuous or dichotomized scale, despite correction for confounders. In patients with obesity, AVP seems not a major contributor to the frequently observed high cortisol levels. Other factors which stimulate the HPA axis or affect cortisol synthesis or breakdown may be more important than the influence of AVP on long-term glucocorticoid levels in obesity.


Outbreeding depression with low genetic variation in selfing Caenorhabditis nematodes.
Theory and empirical study produce clear links between mating system evolution and inbreeding depression. The connections between mating systems and outbreeding depression, whereby fitness is reduced in crosses of less related individuals, however, are less well defined. Here we investigate inbreeding and outbreeding depression in self-fertile androdioecious nematodes, focusing on Caenorhabditis sp. 11. We quantify nucleotide polymorphism for nine nuclear loci for strains throughout its tropical range, and find some evidence of genetic differentiation despite the lowest sequence diversity observed in this genus. Controlled crosses between strains from geographically separated regions show strong outbreeding depression, with reproductive output of F1s reduced by 36% on average. Outbreeding depression is therefore common in self-fertilizing Caenorhabditis species, each of which evolved androdioecious selfing hermaphroditism independently, but appears strongest in C. sp. 11. Moreover, the poor mating efficiency of androdioecious males extends to C. sp. 11. We propose that self-fertilization is a key driver of outbreeding depression, but that it need not evolve as a direct result of local adaptation per se. Our verbal model of this process highlights the need for formal theory, and C. sp. 11 provides a convenient system for testing the genetic mechanisms that cause outbreeding depression, negative epistasis, and incipient speciation.


Machos and sluts: gender, sexuality, and violence among a cohort of Puerto Rican adolescents.
During the past decade, interpersonal violence increasingly has become a public health concern. As a result, prevention programs now aim to decrease violence among diverse populations. This article describes the beliefs and rationale for gender-based violence among a cohort of low-income, predominantly second-generation, mainland Puerto Rican adolescents. Based on a three-year (1989-91) ethnographic study, the findings describe how these young people, through the use of gender-based social constructs such as "machos" and "sluts," justify violence by linking it to beliefs about gender roles, sexuality, and biology, and thus perpetuate gender-role conformity, particularly heterosexual male dominance. The findings suggest that if the public health community is going to reduce gender-based violence among Puerto Rican youth, it needs to acknowledge that gender and sexuality are important ingredients that support violence and avoid a simplified and stereotypical model of culture that ignores other social factors and changes in traditional Latino gender roles.


SGLT2 inhibitors and risk of stroke in patients with type 2 diabetes: A systematic review and meta-analysis.
The effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors on risk of stroke have not been conclusively established. Therefore, we conducted a meta-analysis to evaluate the effects of SGLT2 inhibitors on stroke risk in patients with type 2 diabetes mellitus (T2DM) by searching available randomized trials in PubMed, Embase, CENTRAL, Web of Science, Scopus and ClinicalTrials.gov databases. We identified 32 eligible trials involving 75 540 participants. The incidence of stroke in groups receiving SGLT2 inhibitor monotherapy or combination therapy did not differ significantly from that in control groups, with a relative risk (RR) of 1.01 and 1.0, respectively. Three SGLT2 inhibitors were tested, with similar RR values (canagliflozin [RR, 0.91], dapagliflozin [RR, 0.99] and empagliflozin [RR, 1.03]). Subgroup analyses showed that RR values were not affected by gender, age, diabetes duration, BMI or HbA1C levels, but Black patients had a lower incidence of stroke than White or Asian patients. This meta-analysis indicated that SGLT2 inhibitor therapy did not increase stroke incidence, and no significant differences in stroke risk were observed among 3 SGLT2 inhibitors (class effect). However, the small racial disparity requires further study and confirmation.


Abnormal compact myelin in the myelin-deficient rat: absence of proteolipid protein correlates with a defect in the intraperiod line.
The cervical spinal cords of 23-day-old myelin-deficient (md) rats, an X chromosome-linked myelin mutant, and their normal littermates were studied by light and electron microscopy, immunocytochemistry, and in situ hybridization. Light microscopy showed that there were scattered myelinated fibers in the md rat, particularly in the lateral and ventral columns. Ultrastructural examination of these fibers showed that the myelin often had many lamellae that were tightly compacted, but in which the intraperiod line was abnormally fused at most places, resulting in a minor alteration of the myelin periodicity. Immunocytochemical staining of adjacent sections following a variety of fixation methods showed that the myelinated fibers were positive for myelin basic protein but negative for proteolipid protein (PLP). In situ hybridization using cDNA probes to these proteins showed a severe diminution of the mRNAs for both proteins. These findings provide further support for an abnormality in genetic regulation of PLP as has been described in another X chromosome-linked mutant, the jimpy mouse. Despite the lack of PLP, however, a few myelinated fibers are formed in the md rat, but the myelin formed in general lacks a normal intraperiod line, a site at which this protein is thought to be located.


Reconsolidation in a human fear conditioning study: a test of extinction as updating mechanism.
Disrupting reconsolidation seems to be a promising approach to dampen the expression of fear memory. Recently, we demonstrated that disrupting reconsolidation by a pharmacological manipulation specifically targeted the emotional expression of memory (i.e., startle response). Here we test in a human differential fear-conditioning paradigm with fear-relevant stimuli whether the spacing of a single unreinforced retrieval trial relative to extinction learning allows for "rewriting" the original fear association, thereby preventing the return of fear. In contrast to previous findings reported by Schiller et al. (2010), who used a single-method for indexing fear (skin conductance response) and fear-irrelevant stimuli, we found that extinction learning within the reconsolidation window did not prevent the recovery of fear on multiple indices of conditioned responding (startle response, skin conductance response and US-expectancy). These conflicting results ask for further critical testing given the potential impact on the field of emotional memory and its application to clinical practice.


The results of a randomized trial looking at 24 weeks vs 48 weeks of treatment with peginterferon alpha-2a (40 kDa) and ribavirin combination therapy in patients with chronic hepatitis C genotype 1.
Peginterferon-alpha plus ribavirin is the most effective therapy for chronic hepatitis C. This study was designed to evaluate the effect of peginterferon alpha-2a (40 kDa) plus ribavirin on sustained virological response (SVR) when administered for 24 vs 48 weeks in genotype 1 naïve patients. One hundred and seventeen patients were enrolled in this controlled trial. Genotype 1 patients were randomized to 24 weeks treatment vs 48 weeks treatment. Genotype non-1 patients received 24 weeks treatment as an observational group. Outcomes were SVR (defined by hepatitis C virus-RNA-negative at week 24 of follow-up) and tolerability across the study period. The end-of-treatment response was 59% for genotype 1 (24 weeks treatment), 80% for genotype 1 (48 weeks treatment) and 92% for genotype non-1 (24 weeks treatment). The end-of-follow-up response was 19% (95% confidence interval (CI): 7.2-36.4) (genotype 1, 24 weeks) and 48% (95% CI: 30.2-66.9; P = 0.0175) (genotype 1, 48 weeks). Among genotype non-1, SVR was 76% (95% CI: 62.3-86.5). There were no unexpected adverse events. Almost half of the genotype 1 patients achieved an SVR after 48 weeks treatment with peginterferon alpha-2a (40 kDa) and low-dose ribavirin and confirmed that they should be treated for 48 weeks. Safety profile was acceptable.


An international survey on persistent pulmonary hypertension of the newborn: A need for an evidence-based management.
To assess the current practice preferences in diagnosis and management of persistent hypertension of the newborn (PPHN) of neonatologists or pediatricians with expertise in neonatal care. Investigators identified potential participants worldwide through a literature search. They were emailed the URL of an online 25-item questionnaire through the web survey site SurveyMonkey®. Additional respondents were also acquired through a professional online discussion group. The survey was conducted during July - September 2015. Overall, there were 200 respondents from 51 different countries. Of these, the average 2014 mortality rate of the 90 respondents who completed this section of the questionnaire was 8.3% (interquartile range (IQR): 0-20.3). Echocardiography together with pre-to-post ductal oxygen pulse oximetry (SpO2) gradient was the most common PPHN diagnostic method. The most frequent first-line pulmonary vasodilator was inhaled nitric oxide (155/199, 77.9%). Oral sildenafil was most commonly used as second-line adjunctive therapy by 46.3% (81/175). Dopamine (139/198, 70.2%) was chosen to be the initial inotropic agent and normal saline (191/199, 96.0%) was the preferred initial fluid resuscitation for hypotension. Sedation and analgesia were routinely used for PPHN treatment. Twenty-one percent (42/199) of respondents also used muscle relaxants to control respiratory distress. The most commonly used targets for partial pressure of oxygen, partial pressure of carbon dioxide, SpO2 and hemoglobin were 71-80 mmHg (60/197, 30.4%), 36-45 mmHg (100/199, 50.2%), 91-95% (111/199, 55.8%), and 13-15 gm/dL (156/196, 79.6%), respectively. This survey shows that the management of PPHN varies widely around the world. The major PPHN diagnostic method is echocardiography together with bedside SpO2 monitoring. The study numbers show the main differences are between developed and developing countries. Further studies exploring evidence-based principles of diagnosis and management in PPHN are warranted.


[Genetic polymorphism in Gilbert-Meulengracht syndrome (GMS)].
N-Acetylation and debrisoquine hydroxylation phenotypes were determined in 54 patients with Gilbert's syndrome and in 247 (sulfamethazine) and 76 (debrisoquine) non-related healthy volunteers, respectively. 40 (74.1%) of the patients and 135 (54.7%) of healthy volunteers were slow acetylators (chi 2 = 6.87). In patients, the cumulative urinary excretion (CUE) of sulfamethazine (0-6 hours) was significantly reduced. No differences between the debrisoquine poor metabolizers were observed: Gilbert's syndrome 5/54 (9.3%), healthy volunteers 5/76 (6.6%). The metabolic ratios were similar in both groups as well as the CUE of debrisoquine and its metabolite. Gilbert's syndrome seems to be related in some way to N-acetylation but not to debrisoquine hydroxylation polymorphism.


Surface chemistry and structure of purified, ozonized, multiwalled carbon nanotubes probed by NEXAFS and vibrational spectroscopies.
Understanding of oxidative processes such as solution-phase ozonolysis in multiwalled carbon nanotubes (MWNTs) is of fundamental importance in devising applications of these tubes as components in composite materials, as well as for development of cutting and filling protocols. We present here an evaluation of various spectroscopic tools to study the structure and composition of functionalized nanotubes. We demonstrate near-edge X-ray absorption fine structure (NEXAFS) spectroscopy as a particularly useful and effective technique for studying the surface chemistry of carbon nanotubes.


A Highly Conserved Epitope (RNNQIPQDF) of Porcine teschovirus Induced a Group-Specific Antiserum: A Bioinformatics-Predicted Model with Pan-PTV Potential.
Porcine teschovirus (PTV) is an OIE-listed pathogen with 13 known PTV serotypes. Heterologous PTV serotypes frequently co-circulate and co-infect with another swine pathogen, causing various symptoms in all age groups, thus highlighting the need for a pan-PTV diagnostic tool. Here, a recombinant protein composed of a highly conserved "RNNQIPQDF" epitope on the GH loop of VP1, predicted in silico, and a tandem repeat of this epitope carrying the pan DR (PADRE) and Toxin B epitopes was constructed to serve as a PTV detection tool. This recombinant GST-PADRE-(RNNQIPQDF)n-Toxin B protein was used as an immunogen, which effectively raised non-neutralizing or undetectable neutralizing antibodies against PTV in mice. The raised antiserum was reactive against all the PTV serotypes (PTV-1-7) tested, but not against members of the closely related genera Sapelovirus and Cardiovirus, and the unrelated virus controls. This potential pan-PTV diagnostic reagent may be used to differentiate naturally infected animals from vaccinated animals that have antibodies against a subunit vaccine that does not contain this epitope or to screen for PTV before further subtyping. To our knowledge, this is the first report that utilized in silico PTV epitope prediction to find a reagent broadly reactive to various PTV serotypes.


Teaching Ethics to Pediatric Residents: A Literature Analysis and Synthesis.
Ethics education rarely exists in pediatric resident curricula, although ethical conflicts are common in the clinical practice. Ethics education can prepare residents to successfully handle these conflicts. We searched for methods in teaching ethics to clinical and especially pediatric residents, and identified recurring barriers to ethics teaching and solutions to overcome them. Literature from 4 electronic databases with peer-reviewed articles was screened in 3 phases and analyzed. The literature included papers referring to applied methods or recommendations to teaching ethics to clinical residents, and on a second level focusing especially on pediatrics. An analysis and critical appraisal was conducted. 3 231 articles were identified. 96 papers were included. The applied learning theory, the reported teaching approaches, the barriers to teaching ethics and the provided solutions were studied and analyzed. We recommend case-based ethics education, including lectures, discussion, individual study; regular teaching sessions in groups, under supervision; affiliation to an ethics department, institutional and departmental support; ethics rounds and consultations not as core teaching activity; recurring problems to teaching ethics, primarily deriving from the complexity of residential duties to be addressed in advance; teaching ethics preferably in the first years of residency. We may be cautious generalizing the implementation of results on populations with different cultural backgrounds.


Technical note: The use of an accelerometer for measuring step activity and lying behaviors in dairy calves.
Calf behaviors such as step activity, lying bouts, and lying time may be an indicator of calf health and welfare. To reduce time-consuming visual observations, the use of behavioral monitoring systems have been developed to capture these data. Previous studies have validated lying behaviors using an accelerometer (HPG; HOBO Pendant G data logger, Onset Computer Corp., Bourne, MA) in calves. However, the HPG does not measure step activity. The objectives of this study were to (1) validate step activity, lying bouts, and lying time of AfiTag II (AT2; AfiTag II, Afimilk Ltd., Kibbutz Afikim, Israel) to observations from video, and (2) to compare the behavioral data from AT2 to the HPG. Calves (n=5) were group housed with an automatic calf feeder. Video cameras were installed at both sides of the pen, and observations were analyzed for 7h/calf. The AT2 and the HPG were both attached to the lateral side of the right rear leg of 5 calves, and data were recorded for 10 d. The full 10-d data set was used to examine correlations for lying bouts and lying time between AT2 and the HPG. The HPG was set at a 60-s sampling interval and the output was analyzed both unfiltered as well as utilizing a 1-min event filter to remove potentially erroneous readings. The AT2 recorded step activity, lying bouts, and lying time, and summarized these behaviors in 15-min periods. The AT2 recorded lying time in 3-min intervals, which were then automatically summarized in 15-min periods. The correlations of step activity, lying bouts, and lying time between video recordings and AT2 were 0.99. For the second objective, correlations between AT2 and the HPG were 0.99 for lying time and 0.93 for lying bouts. The 1-min event filter resulted in a 0.03 improvement in correlations for lying bouts between the HPG and AT2. The high correlation between video recordings and AT2 suggest that this device can be used to measure step activity, lying time, and lying bouts in unweaned dairy calves housed in groups.


Drug calculation errors of baccalaureate nursing students.
Most researchers who study the dosage calculation skills of nursing students have looked at the mathematical or computational ability of the students. The authors report findings from a study that analyzed the dosage calculation errors of nursing students from conceptual, mathematical, and measurement perspectives.


[Three-dimensional reconstruction and digitized visualization of the sacrum of women of Uygur and Han nationalities in Xinjiang].
To construct digitized three-dimensional models of the sacrum of women of Uygur and Han nationalities in Xinjiang and assess their value in anatomical studies. Ninety Uygur women and 90 Han women of child-bearing age in Xinjiang were recruited. Digitized three-dimensional reconstruction was used to construct the sacrum models for morphological study and measurement of the physiological indices. The sacral forms of Han women were consistent with the standard anatomical descriptions. Of the Uygur women, 57 (63.3%) showed a standard type of the sacrum, 6 (6.7%) had 4 pairs of sacral foramens, 9 (10%) had 5 pairs of sacral foramens, and 18 (20%) had sacrococcygeal joint abnormalities. There were significant differences in sacral morphologies between the two nationalities (P<0.05). The depths of the sacrum foramen and sacral hiatus were significantly greater in Uyghur women than in Han women (P<0.05). Only a minor proportion of the cases had nonstandard sacral types, found only in Uygur women. Uygur and Han women of child-bearing age in Xinjiang have morphological and anatomical differences of the sacrum, which should be considered in clinical practice.


X-chromosome Forkhead Box P3 polymorphisms associate with atopy in girls in three Dutch birth cohorts.
The Forkhead Box P3 (FOXP3) gene, located on the X-chromosome, encodes a transcription factor that directs T cells toward a regulatory phenotype. Regulatory T cells may suppress development of atopy. We evaluated whether single-nucleotide polymorphisms (SNPs) of FOXP3 are associated with atopy development in childhood. Seven SNPs in FOXP3 were genotyped in 3062 children (51% boys) participating in the Allergenic study, which consists of three Dutch birth cohorts (PIAMA, PREVASC and KOALA). Association of FOXP3 SNPs with total serum IgE and sensitisation (presence of specific serum IgE to egg, milk, and indoor, i.e. house-dust mite, cat, and/or dog allergens) was investigated at ages 1, 2, 4, and 8. Analysis of variance and logistic regression were performed, stratified for gender. Our most consistent finding was observed for sensitisation to egg and indoor allergens. In girls, five FOXP3 SNPs (rs5906761, rs2294021, rs2294019, rs6609857 and rs3761548) were significantly associated with sensitisation to egg at ages 1 and 2 and with sensitisation to indoor allergens at age 2 (P < 0.05), but not at 4 and 8, a finding that was observed across the three cohorts. Rs5906761 and rs2294021 were associated with remission of sensitisation to food allergens in boys, as tested in the PIAMA cohort. This is the first study showing across three cohorts that X-chromosomal FOXP3 genotypes may contribute to development of sensitisation against egg and indoor allergens in girls in early childhood. In addition, an association with remission of sensitisation to food allergens existed in boys only.


Properties of Bacillus cereus spores in reference materials prepared from artificially contaminated spray dried milk.
A reference material for Bacillus cereus was developed based on spray drying of milk artificially contaminated with B. cereus spores. Various properties of the B. cereus spores in the milk powder were determined. The stability of the materials was good with no detectable decrease in the contamination level during 1 1/2 years storage at -20 degrees C or 4 weeks at 22, 30 or 37 degrees C. The homogeneity of the material was found acceptable for use as a reference material. Heat treatments (10 min at 70 or 80 degrees C) and addition of lysozyme to the enumeration medium did not influence the number of spores counted. The germination of the spores depended on the type of medium in which the milk powder was reconstituted, and on the storage period of the material. The suitability of the material was confirmed in a collaborative study. From the results obtained it was concluded that the material developed meets the general requirements set for reference materials and can therefore be used for, among others, testing laboratory performance.


An experimental examination of social contexts and the use of power in a Chinese sample.
Researchers have considered power as a largely corrupting force in organizations. In the present experiment, the authors used the theory of cooperation and competition to investigate the effects of social context on power use in a sample of Chinese participants. The present results support the reasoning that high power compared to low power provides the capacity to assist employees and that cooperative, but not competitive, goals facilitate the motivation of managers to use their power to support employees and to develop managerial conclusions that employees are capable and appreciative. These results suggest limitations to traditional organizational power theories that assume a competitive context between the powerful and those subject to power. Cooperative goals appear to be an important basis for developing the positive face of power in organizations in China and perhaps in other cultures as well.


[CDDP-ip PMUE therapy in gastric cancer cases with liver metastasis].
To reduce liver metastasis and prevent carcinomatous peritonitis, we employed CDDP-ip PMUE therapy in gastric cancer cases with liver metastasis exceeding P0H2S2. Therapy consisted of cis-diammine-dichloroplatinum-ip (CDDP-ip), mitomycin C (MMC), uracil and futraful (UFT) and etoposide. From January 1990 to March 1991, primary lesions were resected in 6 gastric cancer cases with liver metastasis exceeding H2. On the basis of therapy, subjects were classified into 2 groups and the therapeutic effects were compared between them. One group was composed of 3 patients who were placed on CDDP-ip PMUE therapy beginning the 14th day after gastrectomy. The other group was composed of 3 patients who received only UFT oral administration (300 mg/body). As a rule, the following was the CDDP-ip PMUE therapy schedule: CDDP intraperitoneal administration (75 mg/m2) and MMC intravenous injection (10 mg/body) on day 1; etoposide intravenous injection (30 mg/body) on days 2 to 6; and consecutive UFT oral administration (300 mg/body). One case showed MR in a metastatic liver lesion, but treatment proved ineffective in the other cases. Although the 2 patients in the CDDP-ip PMUE therapy group, surviving 315 and 216 days, respectively, died of primary disease and hepatic insufficiency due to an increase in metastatic liver lesions, the third patient has been in good condition for 175 days. This therapy was thought to have prolonged survival. The post-operative survival period in the group of patients receiving only UFT oral administration ranged from 36 to 243 days, with all patients dying of primary disease. The main adverse effects of this therapy (i.e., digestive symptoms, leukopenia, and thrombocytopenia) were slight and transient in all cases. Because the subjects studied were gastric cancer cases exceeding H2, the present investigation resulted in the increase of metastatic liver lesions, a problem to be studied in future.


Application of the polymerase chain reaction (PCR) in the epidemiology of Entamoeba histolytica and Entamoeba dispar infections.
In this paper, we briefly summarize the latest information on the polymerase chain reaction (PCR) as an epidemiologic tool for Entamoeba histolytica and Entamoeba dispar infections. This method which employs DNA template directly extracted from formalin fixed stool specimens offers a good promise for an accurate and reliable epidemiology of the two species. The assay is, sensitive enough to detect as few as five cysts in the stool sample, rapid and selectively differentiates E. histolytica from E. dispar DNA from stool specimens without the need for prior cultivation.


De novo synthesis of 3'-nucleotidase in germinating wheat embryo.
The enzyme 3'-AMP nucleotidase was purified 2,500- to 5,000-fold from extracts of an acetone powder of wheat (Triticum aestivum) embryonic axes germinated for 40 hours. Sodium dodecyl sulfate acrylamide gel electrophoresis and chromatography on Biogel-P100 indicate that the enzyme is monomeric with a molecular weight of 39,000. Extracts of embryos germinated up to 6 hours have only 1% of the 40-hour level of enzyme activity. To see if the increase to 40 hours represents de novo synthesis, extracts were compared for their ability to react with a rabbit antibody prepared against the enzyme. In immunodiffusion tests, 40-hour extracts showed a strong precipitin line coincident with that of the purified enzyme, whereas no precipitation was observed with 1-hour extracts. When the enzyme present in 40-hour extracts was partially inactivated by EDTA, it still blocked the ability of the antibody to inhibit enzyme activity. Extracts of 1-hour embryos, in contrast, were not able to block the inhibitory activity of the antibody. Embryos allowed to take up (35)SO(4) between 40 and 46 hours of germination synthesized (35)S-labeled 3'-nucleotidase. In contrast, no radioactive protein synthesized by embryos during the first 6 hours of germination coincided on gel electrophoresis with the enzyme. These results indicate that the increase in 3'-nucleotidase activity is a consequence of de novo synthesis of the enzyme.


Subjectively felt and objectively measured: Wellbeing in the context of globalization.
The article contributes to the discussion on the relationship between wellbeing (WB) and subjective wellbeing (SWB). Our aim is to develop a method for measuring SWB by creating a moving matrix scale that will be a reference point in different communities' research on SWB. To do so, we analyzed the relationship between objective WB-SWB indicators in 146 countries and other political entities where studies on self-reported life satisfaction (SRLS) were conducted between 2005 and 2017. SRLS values were compared with the values of several of the most frequently accepted objective WB indicators. Additionally, we analyzed variables showing the level of advancement within the process of globalization. The results confirmed that a comparative scale is crucial in determining SWB. Therefore, in many societies, there is a growing awareness of the gap between one's own quality of life and that of others. There is a strong link between HDI and SRLS on a global scale, as well as in the subgroups of high and medium developed countries; this link is missing in poorly developed countries. The disconnection between objective and subjectively perceived change in the situation-that is, the improvement in living standards-does not translate into increased life satisfaction.


Dynamic connectivity in the mitral cell-granule cell microcircuit.
The interactions between excitatory mitral cells and inhibitory granule cells are critical for the regulation of olfactory bulb activity. Here we review anatomical and physiological data on the mitral cell-granule cell circuit and provide a quantitative estimate of how this connectivity varies as a function of distance between mitral cells. We also discuss the ways in which the functional connectivity can be altered rapidly during olfactory bulb activity.


Surgical Fixation of Chondral-Only Fragments of the Knee: A Case Series With a Mean 4-Year Follow-up.
Chondral-only fragments of the knee have traditionally been treated with excision, with or without cartilage restoration procedures. This is because of the historical assumption that cartilage has limited ability to heal to cancellous or subchondral bone. There is now a growing body of evidence supporting surgical fixation of these fragments. We hypothesized that surgical fixation of chondral fragments would result in acceptable rates of healing with improvement in clinical outcome scores. Case series; Level of evidence, 4. Data were collected on 15 surgically fixed chondral-only fragments in 14 patients. We retrospectively collected participant demographic information, lesion characteristics, primary mechanism (osteochondritis dissecans vs traumatic shear injury), fixation methods, reoperation information, second-look arthroscopic information, and clinical outcome scores. The mean clinical follow-up was 3.96 years, with a minimum of 1-year follow-up. All patients underwent follow-up magnetic resonance imaging at a mean of 2 years after the index procedure. The mean age of our cohort was 17.7 years. We found an 80% survival rate for fixation of the fragments at a mean 4-year follow-up. There were statistically significant improvements in postoperative Knee injury and Osteoarthritis Outcome Score and Tegner scores compared with preoperative scores. Follow-up magnetic resonance imaging scans showed complete healing in 10 knees, partial healing in 2 knees, and loss of fixation in 3 knees. Second-look arthroscopic surgery of 3 knees for reasons other than fragment symptoms showed healing of the fragment, while arthroscopic surgery of 3 symptomatic knees showed loss of fixation. Surgical fixation of chondral-only lesions showed an 80% success rate with improvements in the KOOS and Tegner scores.


Triterpene saponins from Craniotome furcata.
Three saponins, craniosaponin A (1) and buddlejasaponins Ia (2) and I (3) were isolated from the n-butanol soluble fraction of Craniotome furcata for the first time. Among them, craniosaponin A (1) was identified to be a new compound. The structure of craniosaponin A was assigned mainly by spectral methods. A preliminary assay in vitro was applied to evaluate their cytotoxicity against several tumor cell-lines.


Angiogenic Biomarkers for Risk Stratification in Women with Preeclampsia.
Preeclampsia is a leading cause of maternal and neonatal mortality and morbidity worldwide. Diagnosis of the condition is currently limited to utilization of nonspecific signs and symptoms. However, identification of potential pathogenic biomarkers may support earlier diagnosis and ultimately improved prognosis. The current models of preeclampsia suggest that the disease has components of abnormal placentation, a degree of angiogenic imbalance and endothelial dysfunction. Angiogenic factors such as soluble fms-like tyrosine kinase-1 and soluble endoglin increase while placental growth factor concentrations decrease in the circulation weeks before the onset of the disease. Multiple studies have looked at the capacity of angiogenic factors for the prediction of preeclampsia and adverse pregnancy outcomes. The goal of this review is to focus on the role of angiogenic factors in the pathogenesis of preeclampsia and use of angiogenic biomarkers for risk stratification, diagnosis, and prognosis of the disease.


Simian virus 40 and malignant mesothelioma (Review).
Simian virus 40 (SV40) was recognized as a contaminant of early poliovirus vaccines that were provided to millions of individuals in Europe and in the USA between 1955 and 1963. SV40, a DNA virus of the family of papovaviridae, was proven to be oncogenic in rodents and able to transform human and animal cells in vitro. In 1993 SV40 was accidentally discovered to produce mesotheliomas in hamsters when it was injected in visceral cavities. Afterwards, SV40 DNA sequences were detected with significative frequency in human pleural mesotheliomas by using polymerase chain reaction (PCR) and then SV40 DNA oncogenicity was associated with its large T antigen (Tag). This finding was confirmed by many laboratories, while a few research groups failed to replicate these data and argued that the SV40 DNA detection might be a PCR contamination artefact. In this review the dispute is examined in the light of recent experiments performed to identify molecular and cellular aspects of carcinogenicity and/or co-carcinogenicity of SV40 in human mesothelioma.


Intensity modulated radiotherapy in carcinoma cervix with metastatic para-aortic nodes: an institutional experience from a Regional Cancer Centre of Eastern India.
Cervical cancer is a major health problem, especially in developing countries like India. Extended field radiotherapy (EFRT) for cancer cervix treatment remains a challenging task for radiation oncologists. In the last decade studies have shown that EFRT using intensity modulated radiotherapy (IMRT) is feasible in treating gynaecological malignancies but there is a dearth of literature on this specific topic from this part of the world where patient profile differs greatly in several aspects from that of the western world. The aim of the study was evaluation of treatment response and toxicity profile in cases of carcinoma cervix with metastatic para-aortic nodes treated with intensity modulated radiotherapy technique. In this retrospective study the treatment records of 45 para-aortic node positive cervical cancer patients treated with EFRT (IMRT) and concurrent cisplatin were analysed for evaluation of loco-regional control and toxicities. Forty-four patients received full course of treatment. Among those 44 patients, 93.2% achieved complete response. Overall, the treatment was tolerated well and toxicities were within acceptable limits. Acute grade 3-4 toxicities were observed mostly in the form of anaemia and leucopenia. Most common late toxicities were those of small and large intestine. EFRT with concurrent chemotherapy was successfully delivered for para-aortic nodes positive cervical cancer patients in Indian scenario where under-nutrition, infection, anaemia and several other factors adversely influence treatment outcome. Pelvic and para-aortic control rates were satisfactory. The technique was associated with an acceptable acute and late toxicity profile.


NF-kappaB modulates aquaporin-2 transcription in renal collecting duct principal cells.
Renal tubulo-interstitial inflammation is frequently associated with polyuria and urine concentration defects. This led us to investigate the effects of the major pro-inflammatory nuclear factor kappaB (NF-kappaB) pathway on aquaporin 2 (AQP2) expression by the collecting duct. Using immortalized collecting duct principal cells (mpkCCDcl4), we found that, acting independently of vasopressin, activation of NF-kappaB by lipopolysaccharide (LPS) decreased AQP2 mRNA and protein levels in a time- and dose-dependent manner but did not decrease AQP2 mRNA stability. Consistently, constitutively active IkappaB kinase beta decreased AQP2 expression. The LPS-induced decrease in AQP2 mRNA levels was confirmed in rat kidney slices and was reproduced both under conditions of elevated cAMP concentration and V(2) receptor antagonism. Computer analysis of the AQP2 promoter revealed two putative kappaB elements. Mutation of either kappaB element abolished the LPS-induced decrease of luciferase activity in cells expressing AQP2 promoter-luciferase plasmid constructs. Chromatin immunoprecipitation revealed that LPS challenge decreased p65, increased p50 and p52, and had no effect on RelB and c-Rel binding to kappaB elements of the AQP2 promoter. RNA-mediated interference silencing of p65, p50, and p52 confirmed controlled AQP2 transcription by these NF-kappaB subunits. We additionally found that hypertonicity activated NF-kappaB in mpkCCDcl4 cells, an effect that may counteract the Tonicity-responsive enhancer binding protein (TonEBP)-dependent increase in AQP2 gene transcription. Taken together, these findings indicate that NF-kappaB is an important physiological regulator of AQP2 transcription.


AGAP3 and Arf6 regulate trafficking of AMPA receptors and synaptic plasticity.
During NMDA receptor-mediated long-term potentiation (LTP), synapses are strengthened by trafficking AMPA receptors to the synapse through a calcium-dependent kinase cascade following activation of NMDA receptors. This process results in a long-lasting increase in synaptic strength that is thought to be a cellular mechanism for learning and memory. Over the past 20 years, many signaling pathways have been shown to be involved in the induction and maintenance of LTP including the MAPK cascade. However, the crucial link between NMDA receptors and the signaling cascades involved in AMPA receptor trafficking during LTP remains elusive. In this study, we aimed to identify and characterize NMDA receptor signaling proteins that link NMDA receptor activation to downstream signaling pathways that lead to trafficking of AMPA receptors. We have identified a novel NMDA receptor interacting signaling protein, AGAP3. AGAP3 contains multiple signaling domains, a GTPase-like domain, a pleckstrin homology domain, and an ArfGAP domain, and exists as a component of the NMDA receptor complex. In addition, we found that AGAP3 regulates NMDA receptor-mediated Ras/ERK and Arf6 signaling pathways during chemically induced LTP in rat primary neuronal cultures. Finally, knocking down AGAP3 expression leads to occlusion of AMPA receptor trafficking during chemically induced LTP. Together, AGAP3 is an essential signaling component of the NMDA receptor complex that links NMDA receptor activation to AMPA receptor trafficking.


Effects of pentanol isomers on the phase behavior of phospholipid bilayer membranes.
Differential scanning calorimetry (DSC) was used to analyze the thermotropic phase behavior of dipalmitoylphosphatidylcholine (DPPC) bilayers in the presence of pentanol isomers. The concentration of each pentanol isomer needed to induce the interdigitated phase was determined by the appearance of a biphasic effect in the main transition temperatures, the onset of a hysteresis associated with the main transition from the gel-to-liquid crystalline phase, and the disappearance of the pretransition. Lower threshold concentrations were found to correlate with isomers of greater alkyl chain length while branching of the alkyl chain was found to increase biphasic behavior. The addition of a methyl group to butanol systems drastically decreased threshold concentrations. However, as demonstrated in the DPPC/neopentanol system, branching of the alkyl chain away from the -OH group lowers the threshold concentration while maintaining a biphasic effect.


Pain Control with Splanchnic Neurolysis in Pancreatic Cancer Patients Unresponsive to Celiac Plexus Neurolysis.
In most instances of abdominal pain associated with pancreatic cancer, pain may become refractory to increasing doses of narcotics. Celiac plexus neurolysis represents an option; however, altered celiac plexus anatomy may render this treatment infeasible or ineffective, where splanchnic nerve neurolysis may represent another option. This study aimed to investigate the outcomes of splanchnic neurolysis in pancreatic cancer patients not responsive to celiac plexus neurolysis. Among all 84 patients who underwent celiac plexus neurolysis for pancreatic cancer pain during the study period, 34 patients did not respond and underwent splanchnic nerve neurolysis under fluoroscopic guidance and thus included in this retrospective study. Stage IV, III, and II disease was present in 38.2%, 47.1%, and 14.7% of the patients. During the study, 88.2% were receiving chemotherapy, whereas none were on radiotherapy. Data for daily narcotic dose equivalents and Visual Analogue Scale (VAS) scores during outpatient visits at baseline, 2 weeks, 2 months, and 3 months were extracted. Pain response rates were 76.5%, 84.4%, and 71.0%, at 2 weeks, 2 months, and 3 months, respectively. A significant and dramatic reduction was seen in VAS scores at 2 weeks (2.8±1.2 versus 6.3±1.1, p<0.001), and this significant decline was maintained for 3 months. Similarly, a significant and dramatic reduction was seen in daily narcotic need at 2 weeks (20.8±32.9 versus 93.4±86.2 mg, p<0.001), which was also maintained during the 3-month follow-up. The procedure was generally well tolerated. Findings of this study suggest that splanchnic neurolysis represents a durable and effective option for pain control in pancreatic cancer patients in whom the neurolysis of the celiac plexus is ineffective. However, these conclusions refer to only preliminary single-center results in a selected patient group; thus, further large studies are warranted.


Obesity, polycystic ovary syndrome and anovulation--how are they interrelated?
Polycystic ovary syndrome remains a mystery with respect to its aetiology, consequences and management. There is an increasing emphasis on its familial origins although the genes involved are unknown. There are significant changes in risk profiles for cardiovascular disease but no clear clinical evidence of morbidity or mortality. There is evidence of improvement in insulin resistance or insulin sensitivity drugs but uncertainty about improvement in pregnancy outcomes. This review looks at the latest advances in understanding polycystic ovary syndrome, particularly in obesity.


Managing chronic airflow obstruction: Part II.
The results of a well-controlled international study have shown no benefit in life expectancy, rate or duration of hospitalizations, lung function, or quality of life when intermittent positive pressure breathing is compared with an air compressor to deliver aerosol bronchodilators. Patients who are accepted on a home oxygen program should be vigorously managed with standard treatment, and only if hypoxemia persists after a month of such therapy should ambulatory oxygen be considered.


External carotid artery embolus with internal carotid artery occlusion with acute ischemic stroke: predictor of cardioembolic etiology.
Arteriograms performed in the Interventional Management of Stroke studies were analyzed for external carotid artery embolus. Two cases were identified and diagnosed as thromboembolic due to a cardiac origin. This is an uncommon but useful finding on angiography which is helpful for further management. It is hypothesized that finding embolus within the external carotid artery on angiography in stroke patients with internal carotid artery occlusion allows confident ascription to a proximal, usually cardiac, source.


GPCRs in the regulation of the functional activity of multipotent mesenchymal stromal cells.
Adipose tissue is one of the tissues in the human body that is renewed during the whole life. Dysregulation of this process leads to conditions such as obesity, metabolic syndrome, and type 2 diabetes. The key role in maintaining the healthy state of adipose tissue is played by a specific group of postnatal stem cells called multipotent mesenchymal stromal cells (MSCs). They are both precursors for new adipocytes and key paracrine regulators of adipose tissue homeostasis. The activity of MSCs is tightly adjusted to the needs of the organism. To ensure such coordination, MSCs are put under strict regulation which is realized through a wide variety of signaling mechanisms. They control aspects of MSC activity such as proliferation, differentiation, and production of signal molecules via alteration of MSC sensitivity to hormonal stimuli. In this regard, MSCs use all the main mechanisms of hormonal sensitivity regulation observed in differentiated cells, but at the same time, several unique regulatory mechanisms have been found in MSCs. In the presented review, we will cover these unique mechanisms as well as specifics of common mechanisms of regulation of hormonal sensitivity in stem cells.


Enediyne antitumor antibiotic maduropeptin biosynthesis featuring a C-methyltransferase that acts on a CoA-tethered aromatic substrate.
The enediyne antitumor antibiotic maduropeptin (MDP) is produced by Actinomadura madurae ATCC 39144. The biosynthetic pathway for the 3,6-dimethylsalicylic acid moiety of the MDP chromophore is proposed to be comprised of four enzymes: MdpB, MdpB1, MdpB2, and MdpB3. Based on the previously characterized biosynthesis of the naphthoic acid moiety of neocarzinostatin (NCS), we expected a biosynthetic pathway featuring carboxylic acid activation by the MdpB2 CoA ligase immediately before its coupling to an enediyne core intermediate. Surprisingly, the MDP aromatic acid biosynthetic pathway employs an unusual logic in which MdpB2-catalyzed CoA activation occurs before MdpB1-catalyzed C-methylation, demonstrating that MdpB1 is apparently unique in its ability to C-methylate a CoA-tethered aromatic acid. MdpB2 is a promiscuous CoA ligase capable of activating a variety of salicylic acid analogues, a property that could be potentially exploited to engineer MDP analogues.


Matrix isolation and spectroscopic characterization of perfluorinated ortho- and meta-benzyne.
The matrix isolation and spectroscopic characterization of two C6F4 isomers, the perfluorinated o-benzyne 4 and the m-benzyne 5, is reported. UV photolysis of tetrafluorophthalic anhydride 6 in solid argon at 10 K results in the formation of CO, CO2, and 1,2-didehydro-3,4,5,6-tetrafluorobenzene (4) in a clean reaction. On subsequent 350 nm irradiation 4 is carbonylated to give the cyclopropenone 7. 1,3-Didehydro-2,4,5,6-tetrafluorobenzene (5) was synthesized by UV irradiation of 1,3-diiodo-2,4,5,6-tetrafluorobenzene (8) via 2,3,4,6-tetrafluoro-5-iodophenylradical 9. Photolysis of 8 in solid neon at 3 K produces good yields of both radical 9 and benzyne 5, while in argon at 10 K no reaction is observed. Thus, the photochemistry in neon at extremely low temperature markedly differs from the photochemistry in argon. The formation of 5 from 8 via 9 is reversible, and annealing the neon matrix at 8 K leads back to the starting material 8. The benzynes 4 and 5 and the radical 9 were characterized by comparison of their matrix IR spectra with density functional theory (DFT) calculations.


Prevalence of nasal symptoms and their relation to self-reported asthma and chronic bronchitis/emphysema.
Little information is available on associations between rhinitis and chronic bronchitis/emphysema (CBE). Self-reported upper airway symptoms, asthma, and CBE were examined in 12,079 adults living in southern Sweden. The response rate was 70% (n=8,469), of whom 33% reported significant nasal symptoms: a blocked nose was reported by 21%; sneezing by 18%; nasal discharge by 17%; and thick yellow nasal discharge by 5.7%. Nasal symptoms and combined nasal and self-reported bronchial disease were generally more common among smokers than nonsmokers. There was little overlap between asthma and CBE, but 46% of those with asthma and 40% of those with CBE had significant nasal symptoms. Best predicting factors (odds ratios >3) for asthma and CBE were nasal symptoms due to exposure to animals and damp/cold air, respectively. One-third of an adult, southern Swedish population, had significant allergic and/or nonallergic nasal symptoms. Nasal symptoms were frequently found to coexist with both asthma and chronic bronchitis/emphysema, suggesting that pan-airway engagement is common in both diseases. Differing associations between types of nasal symptoms and allergic and irritant triggers of nasal symptoms, with regard to asthma and chronic bronchitis/emphysema, emphasize the different natures of these bronchial diseases.


Independent Geometrical Control of Spin and Charge Resistances in Curved Spintronics.
Spintronic devices operating with pure spin currents represent a new paradigm in nanoelectronics, with a higher energy efficiency and lower dissipation as compared to charge currents. This technology, however, will be viable only if the amount of spin current diffusing in a nanochannel can be tuned on demand while guaranteeing electrical compatibility with other device elements, to which it should be integrated in high-density three-dimensional architectures. Here, we address these two crucial milestones and demonstrate that pure spin currents can effectively propagate in metallic nanochannels with a three-dimensional curved geometry. Remarkably, the geometric design of the nanochannels can be used to reach an independent tuning of spin transport and charge transport characteristics. These results laid the foundation for the design of efficient pure spin current-based electronics, which can be integrated in complex three-dimensional architectures.


Genetic polymorphisms of TNFA and IL-1A and generalized aggressive periodontitis.
Virulent bacteria could cause gingival fibroblasts apoptosis through lipopolysaccharide release during generalized aggressive periodontitis (GAgP) development and evolution. We showed that treatment with lipopolysaccharide (LPS, 1 μg/mL) for 30 days induced the decrease in the number of cultured rat gingival fibroblasts as compared to control group, which received no treatment. GAgP is considered to have also a genetic etiology, so the aim of our study was to evaluate if some polymorphisms of tumor necrosis factor-alpha (TNFA) and interleukin 1A (IL-1A) genes are associated with GAgP in a sample of Romanian population. We selected a group of 32 subjects (22 cases and 10 controls) for studying the TNFA (-857) polymorphism and 97 subjects (66 cases and 31 controls) for IL-1A (-889) polymorphism. The single nucleotide polymorphisms were genotyped by real-time polymerase chain reaction for all subjects. The genotype and allelic distribution tended to be equally between the cases and the controls group. Similar results were obtained for the dominant and recessive model. The difference between the two groups did not reach statistic significance for neither of the two studied polymorphisms [p=0.76 for TNFA (-857) and p=0.84 for IL-1A (-889)]. The data suggest that TNFA (-857) C/T and IL-1A (-889) C/T polymorphisms are not associated with susceptibility to GAgP in this Romanian population, potentially because of the small sample size. This is the first such study for Romanian northeastern population.


A prospective study of cutaneous adverse events induced by low-dose alpha-interferon treatment for malignant melanoma.
alpha-Interferon is associated with numerous cutaneous side effects, but the accurate incidence of these complications is not clearly known. A prospective study was designed to evaluate the incidence and clinical pattern of cutaneous side effects in a cohort of patients receiving adjuvant therapy with low-dose interferon for malignant melanoma. A cohort of 33 patients with stage IIA and IIB melanoma treated with low-dose alpha-interferon (3 MIU 3 times a week for 18 months) were prospectively enrolled in a single-center study. The patients responded to a questionnaire on their medical history and were systematically examined for any cutaneous lesions before treatment and every 3 months afterwards. 29/33 patients (87%) experienced 1 or more cutaneous side effects. The most frequent was hair loss and occurred in 16 cases (48.4%). Hair discoloration was noted in 6 cases (18%). Eczematous reactions at injection sites or at remote sites were observed in 13 patients (39%). Pruritus occurred in 10 cases (30%). Xerostomia, Raynaud's phenomenon or livedo reticularis were observed in 10 patients, associated with an increase in circulating autoantibody titer in 2 cases. Some rare side effects were observed: urticaria (1 case) or angioedema (1 case), worsening of preexisting seborrheic dermatitis (3 cases), herpetic recurrence (2 cases), pityriasis versicolor (1 case), worsening of recurrent buccal aphthous ulcer (1 case) and vitiligo (1 case). Cutaneous adverse events during adjuvant immunotherapy of melanoma with low-dose alpha-interferon seem to be frequent but do not result in treatment discontinuation. A good awareness of these side effects may be useful for a more accurate survey and clinical management of patients receiving this treatment.


A new diagnostic technique for adenylosuccinate lyase deficiency.
A convenient and simple method of diagnosing adenylosuccinate lyase (ASL) deficiency is described. This method consists of (1) isolation of SAICA riboside and S-Ado with a cation exchange resin; (2) measurement of the UV absorbance of the ammonia eluate at 270 and 250 nm; (3) calculation of the A270/A250 ratio. If the value of this ratio is less than 0.45, the patient has a normal level of ASL activity. If the value of this ratio is greater than 0.70, the patient has ASL deficiency.


On-Surface Synthesis of Porphyrin-Complex Multi-Block Co-Oligomers by Defluorinative Coupling.
On-surface chemical reaction has become a very powerful technique to synthesize nanostructures by linking small molecules in the bottom-up approach. Given the fact that most reactants are simultaneously activated at certain temperatures, a sequential reaction in a controlled way has remained challenging. Here, we present an on-surface synthesis of multi-block co-oligomers from trifluoromethyl (CF3 ) substituted porphyrin metal complexes. The oligomerization on Au(111) is demonstrated with a combination of bond-resolved scanning probe microscopy and density functional theory (DFT) calculations. Even after the first oligomerization of single monomer unit, the termini of the oligomer keep the CF3 group, which can be used as a reactant for further coupling in a sequential order. Consequently, copper, cobalt, and palladium complexes of bisanthracene-fused porphyrin oligomers were linked with each other in a designed order.


Femoral head reconstruction and revascularization. Treatment for ischemic necrosis.
There is no solution to ischemic necrosis of the femoral head, a condition that leads to collapse, rapid degenerative changes, and subluxation of the hip joint. Core decompression, osteotomy, and various means of femoral head reconstruction have been tried, but the results have been mixed. When ischemic necrosis has led to cartilage indentation and marked collapse, any means of reconstructing the femoral head could be too late. However, if the collapse is not severe, the logical treatment may be the removal of the dead bone and restoration of the bony contents with chip grafts and a vascularized bone strut. A new method of treatment using a vascular pedicled iliac crest strut graft has been used for 13 years. Followup assessments 4 to 12 years later have shown good results with the early involvements, whereas the late collapsed cases showed good control of pain but unsatisfactory maintenance of femoral head integrity. Thus, the technique is recommended for restoring and maintaining femoral head integrity for Stage 3 and early Stage 4 of the disease.


Mental Health Outcomes Amongst Health Care Workers During COVID 19 Pandemic in Saudi Arabia.
Objectives: The study aimed to assess the mental health outcomes and associated factors among health care workers during COVID 19 in Saudi Arabia. Design, Setting, and Participants: We conducted a cross-sectional survey of health care workers from tertiary care and ministry of health Centers across the Central, Eastern, and Western regions of Saudi Arabia. There were 1,130 participants in the survey, and we collected demographic and mental health measurements from the participants. Primary Outcomes and Measures: The magnitude of symptoms of depression, anxiety, and insomnia was measured using the original version of 9-item patient health questionnaire (PHQ-9), the 7-item generalized anxiety disorder scale (GAD-7), and 7-item insomnia severity index (ISI). We use the multiple logistic regression analysis to identify the associated risk factors of individual outcomes. Results: The scores on the PHQ-9 showed that the largest proportion of health care workers (76.93%) experienced only normal to mild depression (50.83 and 26.1%, respectively). The scores on the GAD-7 showed that the largest proportion of health care workers (78.88%) experienced minimal to mild anxiety (50.41 and 28.47%, respectively). The scores on the ISI showed that the largest proportion of health care workers (85.83%) experienced absence to subthreshold insomnia (57.08 and 28.75%, respectively). The risk factors for depression in health care workers were Saudi, living with family, working from an isolated room at home and frontline worker. For anxiety, being female was risk factor and for insomnia, being frontline worker was risk factor. Conclusion: It was observed that the symptoms of depression, anxiety, and insomnia were reported in a lower proportion of health care workers in our study. The participants who were female, frontline workers, Saudi, living with family, and working from home in isolated rooms were predisposed to developing psychological disorders.


A Low-Cost, Accurate, and High-Precision Fluid Dispensing System for Microscale Application.
We present here the development of a low-cost, accurate, and precise fluid dispensing system. It can be used with peristaltic or any other pump to improve the flow characteristics. The dispensing system has a range of 1 to 100 µL with accuracy of ~99.5% and standard deviation at ~150 nL over the entire range. The system developed does not depend on the accuracy or precision of the driving pump; therefore, any positive displacement pump can be used to get similar accuracy and precision, which gives an opportunity to reduce the cost of the system. The dispensing system does not require periodic calibration and can also be miniaturized for microfluidic application. Although primarily designed for aqueous liquid, it can be extended for different nonconductive liquids as well with modifications. The unit is further used for near real-time measurement of lactate from microdialysate. The individual components can easily be made disposable or sterilized for use in biomedical applications.


Base rates for the Selz-Reitan. Index of subtest scatter on the WPPSI-R.
Using the standardization sample of the Wechsler Preschool and Primary Scale of Intelligence-Revised (WPPSI-R) an analysis was done to determine the base rates of occurrence of the Selz-Reitan Index (SRI) of unusual or abnormal scatter. Findings offered support for the use of the WPPSI-R to determine unusually or abnormally large SRIs in clinical practice. However, It was found that the clinical interpretation of obtained indexes depend upon the Full Scale IQ of the individual and the level of the SRI selected for interpretation. Further research on clinical neurological populations is encouraged.


Salmonella-innovative targeting carrier: Loading with doxorubicin for cancer treatment.
Cell- based targeted delivery is recently gain attention as a promising platform for delivery of anticancer drug in selective and efficient manner. As a new biotechnology platform, bacterial ghosts (BGs) have novel biomedical application as targeted drug delivery system (TDDS). In the current work, Salmonellas' BGs was utilized for the first time as hepatocellular cancer (HCC) in-vitro targeted delivery system. Successful BGs loading and accurate analysis of doxorubicin (DOX) were necessary steps for testing the applicability of DOX loaded BGs in targeting the liver cancer cells. Loading capacity was maximized to reach 27.5 µg/mg (27.5% encapsulation efficiency), by incubation of 10 mg BGs with 1 mg DOX at pH 9 in constant temperature (25 °C) for 10 min. In-vitro release study of DOX loaded BGs showed a sustained release (182 h) obeying Higuchi sustained kinetic release model. The death rate (tested by MTT assay) of HepG2 reached to 64.5% by using of 4 μg/ml, while it was about 51% using the same concentration of the free DOX (P value < 0.0001 One-way ANOVA analysis). The proliferative inhibitory concentration (IC50) of the DOX combined formula was 1.328 µg/ml that was about one third of the IC50 of the free DOX (3.374 μg/ml). Apoptosis analysis (tested by flow-cytometry) showed more accumulation in early apoptosis (8.3%) and late apoptosis/necrosis (91%) by applying 1 μg/ml BGs combined DOX, while 1 μg/ml free DOX showed 33.4% of cells in early apoptosis and 39.3% in late apoptosis/necrosis, (P value˃ 0.05: one-way ANOVA). In conclusion, DOX loaded Salmonellas' BGs are successfully prepared and tested in vivo with promising potential as hepatocellular cancer (HCC) targeted delivery system.


Biological property of immune complex to prolong the duration of otitis media with effusion.
This study was designed to evaluate the biological properties of a light molecular weight immune complex, in comparison with that of a heavy molecular weight immune complex. Soluble immune complexes were obtained by mixing horseradish peroxidase (HRP) with guinea pig antiserum to HRP and were divided by gel filtration into several fractions according to their molecular weight (MW). After the chemotactic activity of each fraction was examined in vitro, the lightest and the heaviest MW immune complexes were injected into a guinea pig's left and right superior bulla, respectively. Although a middle ear effusion developed in both the bulla, the histopathological feature of an experimentally induced otitis media with effusion varied with the MW of the injected immune complex. The light MW immune complex proved to be a stronger inducer for a macrophage than the heavy MW immune complex, both in vitro and in vivo, and to have a tendency to persist longer in the tympanic cavity than the heavy MW immune complex. These results suggested that otitis media had a tendency to persist when a light MW immune complex was formed in a middle ear. The light MW immune complex was suspected to be involved in the pathogenesis of otitis media with effusion.


Effects of angiotensin II and bilateral nephrectomy on norepinephrine catabolism in central nervous system.
Effects of angiotensin II (AII) on norepinephrine (NE) catabolism in hypothalamus and medulla oblongata of male rats were studied. 3H-NE uptake, 3H-NE/3H-NE metabolites ratio (NE/MET) and monoamineoxidase (MAO) activity were measured in vitro in both organs. Lack of circulating AII was elicited by means of 48 h bilateral nephrectomy. Pargyline and bilateral nephrectomy increased NE uptake and NE/MET ratio, while in nephrectomized plus pargyline treated groups and additive effect on these results was observed in both organs. All decreased the NE/MET ratio. Pargyline reversed the latter effects of AII. The peptide increased MAO activity in both organs, while bilateral nephrectomy decreased the activity of the enzyme. The results showed that AII modulates NE catabolism by means of MAO activity, eventually at the presynaptic noradrenergic ending sites in the central nervous system.


Comparative studies of the binding of six phthalate plasticizers to pepsin by multispectroscopic approach and molecular modeling.
To explore the binding mechanism of phthalate plasticizers with digestive proteases, their effects on conformation and activity of pepsin by multispectroscopic approach and molecular modeling were investigated. Fluorescence spectra combined with UV-vis and circular dichroism (CD) spectra measurements indicated that the six phthalate plasticizers induced the changes of tertiary and secondary structure of pepsin. The solvent polarity of environment around both Trp and Tyr residues on pepsin were affected by phthalate plasticizers. By analyzing the fluorescence quenching and theoretical calculation data, it was concluded that a binding site exists for each phthalate plasticizer in pepsin with different binding ability. The hydrophobic, hydrogen bonding, and π-π stacking interactions were involved in the interactions between pepsin and phthalate plasticizers. Moreover, the activity assay indicated that phthalate plasticizers were not powerfully inhibitors or activators for pepsin. These studies demonstrated that phthalate plasticizers could cause some negative effects on pepsin. The present studies may provide a way to analyze the biological safety of phthalate plasticizers on digestive proteases or other proteins.


Horizontal transfer of antibiotic resistance genes among gram negative bacteria in sewage and lake water and influence of some physico-chemical parameters of water on conjugation process.
Transfer of antibiotic resistance genes among gram negative bacteria in sewage and lake water and easy access of these bacteria to the community are major environmental and public health concern. The aim of this study was to determine transfer of the antimicrobial resistance genes from resistant to susceptible gram negative bacteria in the sewage and lake water by conjugation process and to determine the influence of some physico-chemical parameters of sewage and lake water on the transfer of these resistance genes. For this reason, we isolated 20 liter of each sewage and lake water from coconut area within university campus and Lingambudi lake respectively in Mysore city, India, during monsoon season and studied different physical parameters of the water samples like pH, temperature, conductivity turbidity and color as well as chemical parameters like BOD, COD, field DO and total chloride ion. The gram negative bacteria were isolated and identified from the above water samples using microbiological and biochemical methods and their sensitivity to different antibiotics was determined by disc diffusion break point assay. Conjugation between two multiple antibiotic resistant isolates Pseudomonas aeuginosa and E. coli as donor and E. coli Rif(r) (sensitive to antibiotics) as recipient were carried out in 5ml sterile sewage and lake water. All isolates were resistant to Am, moderately resistant to Te and E, while majority were sensitive to Cip, Gm and CAZ antibiotics. Horizontal transfer of antibiotic resistance genes by conjugation process revealed transfer of Gm, Te and E resistant genes from Ps. aeruginosa to E. coli Rif(r) recipient with mean frequency of +/- 2.3 x 10(-4) in sewage and +/- 2.6 x 10(-6) in lake water respectively Frequency of conjugation in sewage was two fold more as compared to lake water (p< or =0.05). Co- transfer study revealed simultaneous transfer of above resistant markers together to the recipient cells. As the above results indicate, due to selective pressure in sewage (presence of antibiotics), the isolates from sewage were more resistant to different antibiotics as compared to those from lake water. Furthermore, these resistance genes can transfer to sensitive bacteria by conjugation. Physico-chemical parameters of water may play role in this process.


A new species of Onryza Watson, 1893 (Lepidoptera: Hesperiidae) from China.
A new species, Onryza pesudomaga is described from Zhejiang Province, S. China. The new taxon resembles O. maga which is widely distributed in S. China and Taiwan. Differences and some biological information of the two allied species are given. A key to species of the genus Onryza Watson, 1893 and a distribution map of all the members of this genus are provided.


Turf Quality and Physiological Responses to Summer Stress in Four Creeping Bentgrass Cultivars in a Subtropical Zone.
Cool-season creeping bentgrass (Agrostis stolonifera) has the ability to form fine sports turf, but high temperatures result in summer bentgrass decline (SBD), especially in transitional and subtropical zones. Physiological responses in combination with the alteration in turf quality (TQ) will contribute to a better understanding of SBD in a subtropical zone. Field experiments were conducted from 2017 to 2019 to test the adaptability to summer stress among four cultivars (13M, Penncross, Seaside II, and PA-1). A constant ambient high temperature above 30 °C significantly decreased the TQ of the four cultivars during the summer months in 2017, 2018, and 2019. Significant declines in the chlorophyll content, photochemical efficiency of photosystem II (Fv/Fm and PIABS), leaf relative water content (RWC), and osmotic potential (OP) were induced by summer stress, whereas gradual increases in water-soluble carbohydrates, proline, hydrogen peroxide (H2O2), malondialdehyde (MDA), and electrolyte leakage (EL) were observed in the four cultivars during the summer months. The 13M and Penncross cultivars exhibited better performance than Seaside II and PA-1 in response to summer stress from 2017 to 2019, which is associated with better maintenance of photosynthesis, water status, WSC and proline accumulation, and cell membrane stability. The 13M and Penncross cultivars could be used as potential candidates for turf establishment in a subtropical zone. Physiological responses together with alterations in TQ also provided critical information for the breeding and development of germplasm with heat tolerance in creeping bentgrass species.


The quality of breathing and capnography during laryngeal mask and facemask ventilation.
Clinical measures of ventilation and the relationship between arterial and end-tidal carbon dioxide tensions were studied during inhalational anaesthesia in 18 patients using a laryngeal mask airway or a facemask. Tidal volumes were similar in both groups but expired minute volume, respiratory rate and physiological deadspace ventilation were significantly increased in the facemask group. Both end-tidal and arterial carbon dioxide tensions were higher in the laryngeal mask group. Mean arterial to end-tidal carbon dioxide tension differences ranged from 0.13 to 4.13 kPa in the facemask group and from 0-1.73 kPa with the laryngeal mask airway. Pooled data analysis revealed a better correlation between arterial and end-tidal carbon dioxide tensions during laryngeal mask ventilation as compared to facemask breathing. With both techniques the arterial to end-tidal carbon dioxide tension difference was related to respiratory rate and physiological deadspace ventilation. Estimation of arterial carbon dioxide partial pressure by monitoring end-tidal carbon dioxide tension is more reliable with the laryngeal mask airway than during facemask breathing, in particular at small tidal volumes.


A new caimanine alligatorid from the Middle Eocene of Southwest Texas and implications for spatial and temporal shifts in Paleogene crocodyliform diversity.
Dramatic early Cenozoic climatic shifts resulted in faunal reorganization on a global scale. Among vertebrates, multiple groups of mammals (e.g., adapiform and omomyiform primates, mesonychids, taeniodonts, dichobunid artiodactyls) are well known from the Western Interior of North America in the warm, greenhouse conditions of the early Eocene, but a dramatic drop in the diversity of these groups, along with the introduction of more dry-tolerant taxa, occurred near the Eocene-Oligocene boundary. Crocodyliforms underwent a striking loss of diversity at this time as well. Pre-Uintan crocodyliform assemblages in the central Western Interior are characterized by multiple taxa, whereas Chadronian assemblages are depauperate with only Alligator prenasalis previously known. Crocodyliform diversity through the intervening Uintan and Duchesnean is not well understood. The middle Eocene Devil's Graveyard Formation (DGF) of southwest Texas provides new data from southern latitudes during that crucial period. A new specimen from the middle member of the DGF (late Uintan-Duchesnean) is the most complete cranial material of an alligatorid known from Paleogene deposits outside the Western Interior. We identify this specimen as a caimanine based on notched descending laminae of the pterygoids posterior to the choanae and long descending processes of the exoccipitals that are in contact with the basioccipital tubera. Unlike Eocaiman cavernensis, the anterior palatine process is rounded rather than quadrangular. The relationships and age of this new taxon support the hypothesis that the modern distribution of caimanines represents a contraction of a more expansive early Cenozoic distribution. We hypothesize that the range of caimanines tracked shifting warm, humid climatic conditions that contracted latitudinally toward the hothouse-icehouse transition later in the Eocene.


Depletion of ryanodine-sensitive Ca2+ store activates Ca2+ entry in rat submandibular gland acinar cells.
The existence of ryanodine-sensitive Ca2+ stores and their role in the Ca2+ entry mechanism were examined in the rat submandibular gland acinar cells, using the microfluorimetry of intracellular Ca2+ concentration ([Ca2+]i). In the presence of thapsigargin, a Ca(2+)-ATPase inhibitor of inositol (1, 4, 5) triphosphate (InsP3)-sensitive Ca2+ stores, caffeine caused an increase in [Ca2+]i, which was inhibited by treatment with ryanodine (a ligand to the Ca(2+)-induced Ca2+ release channels). In the cells treated with ryanodine, 1 mM Ca2+ addition to a Ca(2+)-free solution caused a marked increase in [Ca2+]i, which was eliminated by application of Ni2+ or SK & F 96365, suggesting a Ca2+ entry triggered by ryanodine. The maximal change in the net increase in [Ca2+]i caused by the ryanodine-coupled Ca2+ entry, was 104.0 +/- 16.0 nM, which intense was caused by 10 microM ryanodine. Emptying the InsP3-sensitive stores by treatment with thapsigargin also caused Ca2+ entry, which maximally changed [Ca2+]i by 349.6 +/- 15.1 nM. Ten mumol/liter ryanodine was confirmed to cause a release of 45Ca2+ from the parotidic microsomal fraction enriched in endopalsmic reticulum. We propose that ryanodine-sensitive Ca2+ stores are present in rat submandibular gland acinar cells. We further propose that release of Ca2+ from the ryanodine-sensitive stores, which means eventually depletion of the ryanodine-sensitive Ca2+ stores, can activate the Ca2+ entry. The ability for Ca2+ entry coupled with the ryanodine-sensitive Ca2+ stores seems to be about 30% of the ability for Ca2+ entry coupled with the thapsigargin-sensitive Ca2+ stores.


Randomized noninferiority clinical trial evaluating 3 commercial dry cow mastitis preparations: I. Quarter-level outcomes.
The study objective was to compare the efficacy of 3 commercial dry cow mastitis formulations regarding quarter-level prevalence of intramammary infections (IMI) postcalving, cure of preexisting infections over the dry period, prevention of new infections during the dry period, and risk for a clinical mastitis case between calving and 100d in milk (DIM). A total of 1,091 cows (4,364 quarters) from 6 commercial dairy herds in 4 different states (California, Iowa, Minnesota, and Wisconsin) were enrolled and randomized to 1 of the 3 treatments at dry-off: Quartermaster (QT; 1,000,000 IU of procaine penicillin G and 1 g of dihydrostreptomycin; Pfizer Animal Health, New York, NY), Spectramast DC (SP; 500 mg of ceftiofur hydrochloride; Pfizer Animal Health), or ToMorrow Dry Cow (TM; 300mg of cephapirin benzathine; Boehringer Ingelheim Vetmedica Inc., St. Joseph, MO). Quarter milk samples were collected for routine bacteriological culture before dry cow therapy treatment at dry-off, 0 to 6 DIM, and 7 to 13 DIM and an on-farm record-keeping system was used to retrieve data on clinical mastitis cases. Noninferiority analysis was used to evaluate the effect of treatment on the primary outcome, risk for a bacteriological cure during the dry period. Multivariable logistic regression techniques were used to describe the effect of treatment on risk for presence of IMI postcalving and risk of a new IMI during the dry period. Cox proportional hazards regression was used to describe the effect of treatment on the risk and time for quarters to experience an episode of clinical mastitis between calving and 100 DIM. The overall crude quarter-level prevalence of infection at dry-off was 19.2%. The most common pathogen isolated from milk samples at dry-off was coagulase-negative Staphylococcus, followed by Aerococcus spp. and other Streptococcus spp. Noninferiority analysis showed no effect of treatment on risk for a cure between dry-off and calving [least squares means (LSM): QT=93.3%, SP=92.6%, and TM=94.0%] and secondary analysis showed no effect of treatment on risk for presence of an IMI at 0 to 6 DIM (LSM: QT=16.5%, SP=14.1%, and TM=16.0%), risk for development of a new IMI between dry-off and 0 to 6 DIM (LSM: QT=14.8%, SP=12.3%, and TM=14.2%), or risk of experiencing a clinical mastitis event between calving and 100 DIM (LSM: QT=5.3%, SP=3.8%, and TM=4.1%). In conclusion, no difference was observed in efficacy among the 3 products evaluated when assessing the aforementioned quarter-level outcomes.


Adult neuroblastoma complicated by increased intracranial pressure: a case report and review of the literature.
Neuroblastoma is the third most commonly occurring malignancy of the pediatric population, although it is extremely rare in the adult population. In adults, neuroblastoma is often metastatic and portends an extremely poor overall survival. Our case report documents metastatic neuroblastoma occurring in a healthy 29-year-old woman whose course was complicated by an unusual presentation of elevated intracranial pressures. The patient was treated with systemic chemotherapy, I(131) metaiodobenzylguanidine (MIBG) radiotherapy, and autologous stem cell transplant (SCT). Unfortunately the patient's response to therapy was limited and she subsequently died. We aim to review neuroblastoma in the context of increased intracranial pressure and the limited data of neuroblastoma occurring in the adult population, along with proposed treatment options.


Pathology practice and pharmacogenomics.
New technologies emerging from the Human Genome Project and the rapidly expanding direct-to-consumer DNA testing have provided a challenging environment for the entry of pharmacogenomics into clinical practice. The traditional pathology laboratory, which is centered around a referring clinician and the patient, is also being reshaped by these developments. These changes are occurring as the shrinking health dollar imposes a greater focus on preventative medicine. For the latter to benefit from genomics requires the community to be engaged, and the development of the disease process identified earlier than otherwise possible. These two prerequisites are now being sought through the concept of 'personalized medicine'. Much has been occurring in a relatively short time frame, and as a consequence, education becomes a major rate-limiting step to change.


The chloroplast-localized phospholipases D α4 and α5 regulate herbivore-induced direct and indirect defenses in rice.
The oxylipin pathway is of central importance for plant defensive responses. Yet, the first step of the pathway, the liberation of linolenic acid following induction, is poorly understood. Phospholipases D (PLDs) have been hypothesized to mediate this process, but data from Arabidopsis (Arabidopsis thaliana) regarding the role of PLDs in plant resistance have remained controversial. Here, we cloned two chloroplast-localized PLD genes from rice (Oryza sativa), OsPLDα4 and OsPLDα5, both of which were up-regulated in response to feeding by the rice striped stem borer (SSB) Chilo suppressalis, mechanical wounding, and treatment with jasmonic acid (JA). Antisense expression of OsPLDα4 and -α5 (as-pld), which resulted in a 50% reduction of the expression of the two genes, reduced elicited levels of linolenic acid, JA, green leaf volatiles, and ethylene and attenuated the SSB-induced expression of a mitogen-activated protein kinase (OsMPK3), a lipoxygenase (OsHI-LOX), a hydroperoxide lyase (OsHPL3), as well as a 1-aminocyclopropane-1-carboxylic acid synthase (OsACS2). The impaired oxylipin and ethylene signaling in as-pld plants decreased the levels of herbivore-induced trypsin protease inhibitors and volatiles, improved the performance of SSB and the rice brown planthopper Nilaparvata lugens, and reduced the attractiveness of plants to a larval parasitoid of SSB, Apanteles chilonis. The production of trypsin protease inhibitors in as-pld plants could be partially restored by JA, while the resistance to rice brown planthopper and SSB was restored by green leaf volatile application. Our results show that phospholipases function as important components of herbivore-induced direct and indirect defenses in rice.


Radioprotection in vitro and in vivo by minicircle plasmid carrying the human manganese superoxide dismutase transgene.
Manganese superoxide dismutase plasmid liposomes (MnSOD-PL) confer organ-specific in vivo ionizing irradiation protection. To prepare for potential intravenous clinical trials of systemic MnSOD-PL for radioprotection in humans, plasmid and bacterial sequences were removed and a new minicircle construct was tested. Minicircle MnSOD was purified and then cotransfected into 32D cl 3 murine interleukin-3-dependent hematopoietic progenitor cells along with another plasmid carrying the neo gene. Cells were selected in G418 (50 microg/ml) and cloned by limiting dilution. Biochemical analysis of minicircle MnSOD-transfected cells showed an MnSOD biochemical activity level of 5.8 +/- 0.5 U/mg compared with 2.7 +/- 0.1 U/mg for control 32D cl 3 cells (p = 0.0039). 32D-mc-MnSOD cells were as radioresistant as full-length MnSOD-PL transgene-expressing 2C6 cells, relative to 32D cl 3 parent cells, with an increased shoulder on the radiation survival curve (n = 4.8 +/- 0.2 and n = 4.6 +/- 0.2, respectively, compared with 1.5 +/- 0.5 for 32D cl 3 cells; p = 0.007). C57BL/6NHsd mice received intraoral mc-MnSOD-PL, mc-DsRed-PL control, full-length MnSOD-PL, or blank-PL and then were irradiated 24 hr later with 31 Gy to the esophagus. Mice receiving mc-MnSOD-PL showed increased survival compared with control mice or mice treated with mc-DsRed-PL (p = 0.0003 and 0.039, respectively), and comparable to full-length MnSOD-PL. Intravenous, systemic administration of mc-MnSOD-PL protected mice from total body irradiation (9.75 Gy). Therefore, minicircle DNA containing the human MnSOD transgene confers undiminished radioprotection in vitro and in vivo.


Operative treatment of combined anterior and posterior cruciate ligament injuries in complex knee trauma: can the cruciate ligaments be preserved?
A retrospective study was performed focusing on operative treatment after combined anterior cruciate ligament (ACL)/posterior cruciate ligament (PCL) injuries. The operative treatment included the preservation of one or both cruciate ligaments. Twenty-eight patients, average age 30 years (range: 12-55 years), were evaluated 5.4 years (range: 1-14 years) postoperatively. Twenty-two operations were performed in patients with acute injuries (<30 days after trauma) and 6 operations in patients with chronic instabilities (>30 days after trauma). Both cruciate ligaments were preserved by suture or refixation in 16 patients. Suture of one and reconstruction of the other cruciate ligament with autologous tendon graft was performed in 12 cases. In addition, 61 procedures (meniscal suture/resection, medial/lateral reconstruction, tendon suture, and open reduction and internal fixation were performed. Postoperative treatment included continuous passive motion and protected weight bearing. Eleven (27% acute, 83% chronic) patients required revision (ACL/PCL reconstruction, osteotomy, and meniscal repair). At follow-up, 43% of the patients were very satisfied and 46% were satisfied. Seventy-one percent (89% preinjury) of the patients were able to maintain intensive and moderate International Knee Documentation Committee (IKDC) activity levels. The IKDC evaluation of the patients (acute %/chronic cases %) was graded for symptoms: A 39% (45/17), B 35% (27/67), C 15% (18/0), and D 11% (9/17); for range of motion: A 42% (36/67), B 42% (50/17), C 16% (14/17), and D 0%; and for ligaments: A 21% (18/17), B 33% (45/0), C 42% (32/83), and D 4% (5/0). Radiographic findings were A 18%, B 41%, and C 41%. Primary repair of acute injuries was superior to the delayed repair of chronic instabilities. Preservation of cruciate ligaments in acute combined ACL/PCL tears results in a satisfying knee function despite distinct residual ligament instability. Although suture of the cruciate ligaments in open technique is a therapeutic option in acute multiligamentous knee injuries, it is not recommended for the treatment of chronic instabilities.


The comparative gastrointestinal response of young children to the ingestion of 25 g sweets containing sucrose or isomalt.
Sugar-free confectionery products containing the low-energy, non-cariogenic sweetener isomalt are widely available in the market place and increasingly aimed at children. However, over-consumption of such products may lead to gastrointestinal symptoms and/or osmotic diarrhoea. Little is known about the gastrointestinal tolerance of children following consumption of isomalt. The aim of the present study was to assess gastrointestinal symptoms in children following consumption of sugar-free confectionery containing isomalt compared with sweets containing sucrose. In a double-blind, randomised, controlled, crossover study, sixty-seven children aged 6-9 years ingested 25 g hard-boiled sweets containing either sucrose or isomalt on two consecutive test days. Isomalt sweets were received as enthusiastically as sucrose sweets and, when given the choice, 97 % of children asked to be given the isomalt or the sucrose sweets on the second test day. Most children did not report multiple symptoms and few experienced symptoms on both days of isomalt consumption. However, significantly more children reported stomach-ache (P<0.01), abdominal rumbling (P<0.025) and passing watery faeces (P<0.001) following consumption of isomalt sweets compared with sucrose sweets. Consumption of 25 g isomalt-containing sweets by children is not associated with significant gastrointestinal effects graded as 'considerably more than usual' or multiple symptoms, but is associated with a laxative effect and increase in symptoms graded as 'slightly more than usual'. For the majority of children in the present study, 25 g isomalt-containing sweets represents an acceptable level of consumption, although some children are sensitive to the effects of isomalt ingestion.


Chemical Weapons Exposures in Iraq: Challenges of a Public Health Response a Decade Later.
An October 14, 2014 article in The New York Times reported that the US Department of Defense (DoD) concealed, for nearly a decade, circumstances surrounding service members' exposure to chemical warfare agents (CWA) while deployed to Iraq in support of Operations Iraqi Freedom and New Dawn from March 13, 2003, to December 31, 2011, and alleged failure of the DoD to provide expedient and adequate medical care. This report prompted the DoD to devise a public health investigation, with the Army Public Health Center (Provisional) as the lead agency to identify, evaluate, document, and track CWA casualties of the Iraq war. Further, the DoD revisited and revised clinical guidelines and health policies concerning CWA exposure based on current evidence-based guidelines and best practices.


Barriers and facilitators to CPR knowledge transfer in an older population most likely to witness cardiac arrest: a theory-informed interview approach.
We sought to identify perceived barriers and facilitators to cardiopulmonary resuscitation (CPR) training and performing CPR among people above the age of 55 years. We conducted semistructured qualitative interviews with a purposive sample of independent-living individuals aged 55 years and older from urban and rural settings. We developed an interview guide based on the constructs of the Theory of Planned Behaviour, which elicits salient attitudes, social influences and control beliefs potentially influencing CPR training and performance. Interviews were recorded, transcribed verbatim and analysed until achieving data saturation. Two independent reviewers performed inductive analyses to identify emerging themes, and ranked them by way of consensus. Demographics for the 24 interviewees: mean age 71.4 years, women 58.3%, urban location 75.0%, single dwelling 58.3%, CPR training 79.2% and prior CPR on real victim 8.3%. Facilitators of CPR training included: (1) classes in a convenient location; (2) more advertisements; and (3) having a spouse. Barriers to taking CPR training included: (1) perception of physical limitations; (2) time commitment; and (3) cost. Facilitators of providing CPR included: (1) 9-1-1 CPR instructions; (2) reminders/pocket cards; and (3) frequent but brief updates. Barriers to providing CPR included: (1) physical limitations; (2) lack of confidence; and (3) ambivalence of duty to act in a large group. We identified key facilitators and barriers for CPR training and performance in a purposive sample of individuals aged 55 years and older.


The year's new drugs and biologics 2017: Part I.
This review presents the 113 new drugs and biologics that were approved or launched for the first time globally in 2017. Fifty-two new drugs and biologics reached their first markets worldwide in 2017. Seven of the new launches were first-in-class agents, meaning the first drug with a novel mechanism of action to be approved and launched anywhere in the world. In addition, 36 notable line extensions (i.e., new indications, new combinations and new formulations of previously marketed products) were introduced last year. The remaining 25 products discussed in this article were approved for the first time during the year just passed, but had not yet been launched as of December 31, 2017. The United States was the most active market for new drugs, and oncology was the most active therapeutic group. Information on these new arrivals is covered in depth in part I of our annual review of the pharma and biotech industry.


Surveillance for highly pathogenic H5 avian influenza virus in synanthropic wildlife associated with poultry farms during an acute outbreak.
In November 2014, a Eurasian strain H5N8 highly pathogenic avian influenza virus was detected in poultry in Canada. Introduced viruses were soon detected in the United States and within six months had spread to 21 states with more than 48 million poultry affected. In an effort to study potential mechanisms of spread of the Eurasian H5 virus, the United States Department of Agriculture coordinated several epidemiologic investigations at poultry farms. As part of those efforts, we sampled synanthropic birds and mammals at five infected and five uninfected poultry farms in northwest Iowa for exposure to avian influenza viruses. Across all farms, we collected 2,627 samples from 648 individual birds and mammals. House mice were the most common mammal species captured while house sparrows, European starlings, rock pigeons, swallows, and American robins were the most commonly captured birds. A single European starling was positive for Eurasian H5 viral RNA and seropositive for antibodies reactive to the Eurasian H5 virus. Two American robins were also seropositive. No mammal species showed evidence of infection. These results indicate synanthropic species merit further scrutiny to better understand potential biosecurity risks. We propose a set of management practices aimed at reducing wildlife incursions.


[Localization of embryonal acetylcholinesterase during the early development of the chick embryo].
The presence of "embryonic" acetylcholinesterase activity, as described by Drews (1975) was investigated during early chick embryonic development, mainly in the following systems: a) primitive streak and Hensen's node during gastrulation movements; b) area opaca during blood islets and vessels differentiation; c) mesoderma of lateral laminae, during delamination movements. The demonstration of enzymic activity was performed with slightly modified histochemical methods. The enzyme was thus localized around the nuclei, in the cytoplasm and associated to plasma membrane of cells engaged in morphogenetic movements. The enzyme activity localized at the plasma membrane was supposed to be involved in the regulation of membrane functions concerning intercellular communications, such as inductive message, perhaps mediated by ion fluxes.