Toxicological evaluation of new calcium antagonists: 2-substituted 3-dimethylamino-5,6-methylenedioxyindenes.
The 2-n-propyl (pr) and 2-n-butyl (bu) methylenedioxyindenes (MDIs) developed in our laboratories are intracellular calcium antagonists with coronary dilating and antiarrhythmic actions. Acute toxicity studies resulted, in mice, in an iv LD50 of 40 and 32 mg/kg for pr-MDI and bu-MDI, respectively, and an ip LD50 of 185 mg/kg for both MDIs. In rats, the ip LD50 was 175 and 240 mg/kg for pr-MDI and bu-MDI, respectively. An iv dose of 16 mg/kg decreased motor activity and prolonged barbiturate sleeping time in mice, but did not affect conditioned avoidance behavior or motor coordination tests. In sub-acute toxicity studies, rats received daily for 4 weeks 26.25 or 52.5 mg/kg ip of either MDIs, while mice received 23.13 or 46.25 mg/kg ip of either MDIs. No alterations were observed in serum alkaline phosphatase, glutamic-pyruvic transaminase, glutamic-oxalacetic transaminase, creatine phosphokinase, bilirubin, chloride, cholesterol, uric acid, prothrombin time, and bromsulphalein retention. Blood glucose was slightly lowered. Serum calcium was slightly lowered in male mice. The higher dose of pr-MDI elevated serum lactate dehydrogenase in rats. Both MDIs elevated serum isocitric dehydrogenase in male rats. Light microscopic examination of brain, kidney, liver, spleen, intestine, stomach, and myocardium showed no anomalies resulting from the 4-week MDI treatment, and electron microscopic examination of hepatocytes revealed no deleterious effects of either MDIs.


Routine dipstick urinalysis in daily practice of Belgian occupational physicians.
Little work has been done to assess the quality of health care and the use of evidence-based methods by occupational physicians in Belgium. Therefore, the main objective is to describe one aspect of occupational health assessments, namely the common use of dipstick urinalysis, and to compare the current practice with international guidelines. A self-administered questionnaire was mailed to 211 members of the Scientific Association of Occupational Medicine in the Dutch speaking part of Belgium. A total of 120 occupational physicians responded, giving a response rate of 57%. Dipstick urinalysis was a routine investigation for the vast majority of physicians (69%). All test strips screened for protein and in 90% also for blood. Occupational health services offered clinical tests to satisfy customer wants as international guidelines do not recommend screening for haematuria and proteinuria in asymptomatic adults. A lack of knowledge concerning positive testing and referral criteria was demonstrated in almost half of the study participants. Belgian occupational physicians still routinely perform dipstick testing although there is no evidence to support this screening in healthy workers. To practice evidence-based medicine, occupational physicians need more instruction and training. Development and implementation of more guidelines is not only of use for the individual practitioner, it may also enhance professionalization and efficiency of occupational health care.


First Report of Leaf Spot Disease in Coconut Seedling Caused by Bipolaris setariae in China.
Coconut (Cocos nucifera L.), an important oilseed as well as a multipurpose perennial plantation crop, is distributed and planted in humid tropical areas. In October 2012, a new leaf spot disease was observed on 3-year-old coconut seedlings in Wenchang, Hainan Province, China. The symptom first appeared as spindly or elliptical and brown flecks with water-soaked lesions that became yellow with the progress of the disease. In the later stage of the disease, the lesions merged together, gradually expanding to the leaf apex. In recent years, the disease has been prevalent in all the nursery gardens surveyed. Once young leaves got infected and nearly all the leaves of the tree showed diseased symptoms, the coconut eventually became defoliated. The pathogen was isolated from the lesion margin, surface sterilized with 75% ethanol and 0.1% mercury bichloride, washed by sterile distilled water, and then placed excising pieces of leaves from the leision margin onto potato dextrose agar (PDA). Plates were incubated at 25°C for 4 days. After 7 days, the colony was grayish black and produced black pigment in the medium. Aerial mycelium was fluffy, septate, and branched, the conidiophores were slightly flexuous or straight, 5 to 11 μm thick, and produced curved, spindle-shaped, or fusiform, septate conidia with 4 to 10 septa, measuring 39 to 86 × 9 to 16 μm, with a slightly protuberant hilum, truncated. Based on the symptoms and mycelial and conidial characters above, the fungus was identified as Bipolaris setariae (1). The pathogenicity was established and repeated for six times by following Koch's postulates. Two 1-year-old coconut seedlings were washed with sterilized water and six leaves were wounded with a sterile needle and then inoculated by spraying them with a suspension of conidia of the isolate. The seedlings were kept in two incubators at 25°C for 12 days. Inoculated leaves showed typical symptoms similar to those described above. The pathogen was re-isolated from inoculated leaves. Morphological characteristics were identical to the original isolated fungus. In contrast, the control leaves did not show any symptoms. The genomic DNA of this fungus was extracted, amplification of the internal transcribed spacer (ITS) region was performed with primer ITS1 and ITS4, and the purified PCR product was sequenced (GenBank Accession No. KJ605157). BLASTn analysis revealed 99% sequence similarity with four B. setariae isolates (HE792936.1, JX462256, GU073108.1, and FJ606786.1). Morphologic characters and sequence analysis of the ITS rDNA confirmed that the pathogen was B. setariae. Bipolaris incurvata has been reported causing disease on coconut (2), but B. setariae was not previously reported on coconut. So far, this is the first report of B. setariae caused coconut seedling leaf spot disease in Hainan, China. References: (1) K. C. da Cunha et al. J. Clin. Microbiol. 50:4061, 2012. (2) A. Kamalakannan et al. New Dis. Rep. 12:18, 2005.


A Comprehensive Health Plan: The Lifestyle Affecting Factors in Iranian Youth.
Factors affecting lifestyle become one of the most priorities of the research field, especially in adolescents and youth. Using a qualitative approach, this study aimed to understand what factors are affecting young people's healthy lifestyle. Using the conventional content analysis, and used the semi-structured in-depth interviews, we conducted a qualitative study to elicit the youth opinion considering their lifestyle affecting factors. Initially, purposeful sampling method was considered for data collection. Participants were selected from volunteered youths 18-30 years whom were selected from the Tehran city. Inclusion criteria for the participants were; (a) willingness to participate in the study, and (b) ability to express experiences. According to findings, although the majority of participants agreed on the important role of lifestyle related behaviors in their healthy life, the lack of essential motivation and the pressure of educational assignments remove it from their daily program priorities. The most important barrier to observing the healthy lifestyle was expressed as; the acceptance of the concept by the individual and the social and economic potential of the individual. It was also suggested that practical interventions should focus on improving more participator engagement of all of the related stakeholders. We proposed the participatory strategies for youth healthy lifestyle promotion. Through which based on a specific needs the assessment of different target groups, designing, development, and implementation of health programs led to more effective interventions.


Assessment of repeatability of a wireless, inertial sensor-based lameness evaluation system for horses.
To determine repeatability of a wireless, inertial sensor-based lameness evaluation system in horses. 236 horses. Horses were from 2 to 29 years of age and of various breeds and lameness disposition. All horses were instrumented with a wireless, inertial sensor-based motion analysis system on the head (accelerometer), pelvis (midline croup region [accelerometer]), and right forelimb (gyroscope) before evaluation in 2 consecutive trials, approximately 5 minutes apart, as the horse was trotted in a straight line. Signal-processing algorithms generated overall trial asymmetry measures for vertical head and pelvic movement and stride-by-stride differences in head and pelvic maximum and minimum positions between right and left sides of each stride. Repeatability was determined, and trial difference was determined for groups of horses with various numbers of strides for which data were collected per trial. Inertial sensor-based measures of torso movement asymmetry were repeatable. Repeatability for measures of torso asymmetry for determination of hind limb lameness was slightly greater than that for forelimb lameness. Collecting large numbers of strides degraded stride-to-stride repeatability but did not degrade intertrial repeatability. The inertial sensor system used to measure asymmetry of head and pelvic movement as an aid in the detection and evaluation of lameness in horses trotting in a straight line was sufficiently repeatable to investigate for clinical use.


The NZB mouse as a model for chronic lymphocytic leukemia.
Chronic lymphocytic leukemia (CLL) is the most common leukemia in the Western world and the only leukemia for which a possible genetic component has been described. Analysis of this genetic component has been hindered by the fact that disease onset normally occurs after age 50. We report here the aged NZB mouse as an animal model for CLL. NZB mice have a genetically regulated, age-dependent onset of clonal, aneuploid cells which are IgM+ and Ly1+ (CD5+ B-cells). Peripheral blood smears from old NZB mice show an increase in circulating lymphocytes and "smudged" or ruptured cells, often seen in human CLL. Electron microscopic examination of these cells shows them to be mature lymphocytes. Light microscopy of the spleen shows infiltration of small lymphocytes and is consistent with CLL pathology. These long-lived, CLL-like cells can be serially passaged into recipient animals. This continued passage occasionally results in the development of a large cell lymphoma detectable in the spleen, lymph nodes, and liver. The histology of this lymphoma is quite distinct from that of the CLL-like cells, but the phenotype is that of an aneuploid CD5+, IgM+ cells. This apparently represents a continued transformation of the CLL-like clone similar to the development of Richter's syndrome in human CLL. Therefore, the NZB mouse can be a valuable tool for the determination of the genetic basis of CLL ontogeny and the conversion of CLL into Richter's syndrome.


Exploration of the structural environment of the iron-sulfur cluster in putidaredoxin by nitrogen-15 NMR spectroscopy of selectively labeled cysteine residues.
Putidaredoxin is a di-iron protein whose paramagnetic region is not well characterized by 1H detected NMR. We have studied the structure of this region in greater detail by directly observed 15N NMR of oxidized and reduced putidaredoxin preparations in which the six cysteine residues are selectively labeled with 15N. A new method for preparation of a stable form of reduced putidaredoxin has been developed for use in NMR. The 15N NMR spectra of the oxidized and reduced forms are characteristically different, and we have measured and compared 15N chemical shifts, spin-lattice relaxation times (T1), and chemical shift/temperature dependences for both forms. Evidence for localized valencies of the iron atoms in the reduced form is presented. From the 15N T1 values of the oxidized form, reduced distances of the cysteine backbone 15N nuclei from the center of the Fe2S2 cluster have been calculated. These distances are consistent with those calculated from X-ray crystal structure data for five ferredoxins, and confirm the structural similarity of the Fe2S2 clusters in putidaredoxin and in these ferredoxins in the oxidized state.


The Universal and Primary Prevention of Foetal Alcohol Spectrum Disorders (FASD): A Systematic Review.
Foetal alcohol spectrum disorder (FASD) comprises multiple neurodevelopmental disorders caused by alcohol consumption during pregnancy. With a global prevalence rate of 7.7 per 1000 population, FASD is a leading cause of prenatal developmental disorders. The extent of physical, mental, and social consequences for individuals with FASD can be vast and negatively affect their social environment, daily life, school, relationships, and work. As treatment for FASD is labour- and cost-intensive, with no cure available, prevention is key in reducing FASD prevalence rates. As most systematic reviews conducted so far have focused on specific FASD risk groups, we investigated the effectiveness of universal FASD prevention and primary preventive strategies. We identified a total of 567 potentially pertinent records through PubMed, Cochrane Library, EBSCO, PubPsych, and DAHTA published from 2010 to May 2020, of which 10 studies were included in this systematic review. Results showed a substantial heterogeneity in the studies' quality, although all preventive measures, except one, proved effective in both increasing knowledge and awareness of FASD, as well as decreasing the risk of an alcohol exposed pregnancy. Limiting factors such as small sample sizes and a lack of behavioural change testing require further studies to support existing evidence for FASD prevention and its implementation, as well as detecting the best course of action for FASD prevention when creating and implementing prevention and intervention approaches.


Effect of single-drug therapy on reduction of left atrial size in mild to moderate hypertension: comparison of six antihypertensive agents.
Cardiac effects of hypertension include increased left ventricular (LV) mass and LV hypertrophy, as well as increased left atrial size, a predictor of stroke and atrial fibrillation. Although literature on reduction of LV mass with antihypertensive therapy is extensive, little information is available on effects of treatment on left atrial size. Patients with mild to moderate hypertension (diastolic blood pressure 95 to 109 mm Hg) were randomly allocated to treatment with atenolol, captopril, clonidine, diltiazem, hydrochlorothiazide, or prazosin in a double-masked trial. Two-dimensional targeted M-mode echocardiography was used to assess left atrial size and LV mass at baseline, 8 weeks, and 1 and 2 years. Longitudinal analysis examined changes in left atrial size from the baseline study, statistically adjusting for age, race, pretreatment left atrial size and LV mass, and serial measurements of systolic blood pressure, body weight, urinary sodium excretion, and physical activity score. Without adjustment for covariates, only hydrochlorothiazide was associated with decreases in left atrial size from baseline at 8 weeks (-1.0 +/- 5.2 mm; P=0.052), 1 year (-2.0 +/- 5.1 mm; P=0.02), and 2 years (4.6+/-7.2 mm; P=0.002). After adjustment for effects of covariates, patients with normal left atrial size had greater reduction (-3.3 mm) in left atrial size at 2 years with hydrochlorothiazide than with any other drug. For patients with left atrial enlargement, left atrial size decreased significantly with hydrochlorothiazide, atenolol, clonidine, and diltiazem at 1 year and with all treatments at 2 years. However, reduction at 2 years was greater with hydrochlorothiazide than with captopril or prazosin. Antihypertensive drugs differ in their effects on left atrial size. Hydrochlorothiazide was associated with greater overall reduction of left atrial size than other drugs effective for the treatment of hypertension. Reduction of left atrial size with therapy is in part independent of factors known to influence left atrial size, including LV mass and reduction of LV mass with treatment. The clinical benefit of reducing left atrial size with antihypertensive treatment remains to be determined.


CpG-enriched plasmid enhances the efficacy of the traditional foot-and-mouth disease killed vaccine.
A CpG-enriched recombinant plasmid (pUC18-CpG) as an adjuvant of FMD killed vaccine was tested for immunization and vaccination challenge in a porcine model. Our preliminary results had indicated that the recombinant plasmid could enhance the humoral immune response triggered by the traditional oil-adjuvant vaccine after the initial inoculation. A subsequent vaccination-challenge test showed an increased PD(50) value. Thus, coadministration of the recombinant plasmid with the oil-adjuvant vaccine helped illicit an immune response earlier than that elicited by giving the vaccine alone. Our results showed that pUC18-CpG can be a potent immunoadjuvant for the traditional FMD killed vaccine and can greatly enhance the traditional vaccine's efficacy when given in combination with it.


Psychoanalysis and Affective Neuroscience. The Motivational/Emotional System of Aggression in Human Relations.
This article highlights the evolutionary biological epistemology in Freud psychoanalytic theory. The concepts of aggressive and sexual drives are cornerstones of the psychoanalytic epistemological system, concerning the motivational/emotional roots of mental functioning. These biological roots of mental functioning, especially with regard to aggressive drive, have gradually faded away from psychoanalytic epistemology, as we show in this article. Currently, however, Neurosciences, and in particular Affective Neuroscience (Panksepp, 1998), can help us to have a better understanding of the biological roots of human mental functioning. The motivational/emotional systems studied by Affective Neuroscience can give a new epistemological foundation to the aggressive drive concept in psychoanalytic theory. Over the course of human evolution, motivational/emotional systems have played a role in social relationships and also in mental functioning. In this regard, among the various types of aggression (ANGER in Panksepp taxonomy 1998) that we consider in our article, inter-male aggression, also named Dominance motivational/emotional system, is that which regulates social interactions between sexually matured adults. This type of aggression acts in complementary connection with FEAR motivational/emotional system that regulate submissive behavior and social defeat, and the latter one is of the more important stressors. The interaction between aggression and FEAR motivational/emotional systems gives rise to agonistic behavior or dominance/submission motivational/emotional system, as we propose in our article. There is now a large literature that identifies in the dynamic of Competitive behavior, which is one of the main factors of mental illness. When social interactions activate the competitive behavior, the subject can perceive himself as "destined to victory" or "destined to defeat," activating either behaviors or emotions connected to the Involuntary Defeat Strategy or Involuntary Dominant Strategy (Sloman, 2002), which we can find in many types of mental disorders, for example, mood disorders or anxiety disorders.


Pott's puffy tumor. A condition still to be considered.
In the era of antibiotics, Pott-Puffy Tumor PPT is a rarely recognized entity. An 11-year-old girl presented with headache, fever for one week, and frontal swelling for 3 days. On examination, she was febrile, congested nasal mucosa with yellowish nasal discharge and frontal swelling; tender not fluctuating with normal eye mobility. Computed tomography CT scan of brain and paranasal sinus revealed opacity of maxillary, left ethmoid, frontal sinus opacity and epidural collection in the right frontal region with post contrast enhancement. An extracranial superficial swelling with fluid collection at the same level of epidural collection. The patient underwent bilateral antral washout and left frontal sinus trephination, which had resulted into a complete resolving of symptoms and an avoidance of further invasive surgical intervention.


Anion-Mediated Photophysical Behavior in a C60 Fullerene [3]Rotaxane Shuttle.
By addressing the challenge of controlling molecular motion, mechanically interlocked molecular machines are primed for a variety of applications in the field of nanotechnology. Specifically, the designed manipulation of communication pathways between electron donor and acceptor moieties that are strategically integrated into dynamic photoactive rotaxanes and catenanes may lead to efficient artificial photosynthetic devices. In this pursuit, a novel [3]rotaxane molecular shuttle consisting of a four-station bis-naphthalene diimide (NDI) and central C60 fullerene bis-triazolium axle component and two mechanically bonded ferrocenyl-functionalized isophthalamide anion binding site-containing macrocycles is constructed using an anion template synthetic methodology. Dynamic coconformational anion recognition-mediated shuttling, which alters the relative positions of the electron donor and acceptor motifs of the [3]rotaxane's macrocycle and axle components, is demonstrated initially by 1H NMR spectroscopy. Detailed steady-state and time-resolved UV-vis-IR absorption and emission spectroscopies as well as electrochemical studies are employed to further probe the anion-dependent positional macrocycle-axle station state of the molecular shuttle, revealing a striking on/off switchable emission response induced by anion binding. Specifically, the [3]rotaxane chloride coconformation, where the ferrocenyl-functionalized macrocycles reside at the center of the axle component, precludes electron transfer to NDI, resulting in the switching-on of emission from the NDI fluorophore and concomitant formation of a C60 fullerene-based charge-separated state. By stark contrast, in the absence of chloride as the hexafluorophosphate salt, the ferrocenyl-functionalized macrocycles shuttle to the peripheral NDI axle stations, quenching the NDI emission via formation of a NDI-containing charge-separated state. Such anion-mediated control of the photophysical behavior of a rotaxane through molecular motion is unprecedented.


Contrasted patterns of selection on MHC-linked microsatellites in natural populations of the Malagasy plague reservoir.
Plague (Yersinia pestis infection) is a highly virulent rodent disease that persists in many natural ecosystems. The black rat (Rattus rattus) is the main host involved in the plague focus of the central highlands of Madagascar. Black rat populations from this area are highly resistant to plague, whereas those from areas in which the disease is absent (low altitude zones of Madagascar) are susceptible. Various lines of evidence suggest a role for the Major Histocompatibility Complex (MHC) in plague resistance. We therefore used the MHC region as a candidate for detecting signatures of plague-mediated selection in Malagasy black rats, by comparing population genetic structures for five MHC-linked microsatellites and neutral markers in two sampling designs. We first compared four pairs of populations, each pair including one population from the plague focus and one from the disease-free zone. Plague-mediated selection was expected to result in greater genetic differentiation between the two zones than expected under neutrality and this was observed for one MHC-class I-linked locus (D20Img2). For this marker as well as for four other MHC-linked loci, a geographic pattern of genetic structure was found at local scale within the plague focus. This pattern would be expected if plague selection pressures were spatially variable. Finally, another MHC-class I-linked locus (D20Rat21) showed evidences of balancing selection, but it seems more likely that this selection would be related to unknown pathogens more widely distributed in Madagascar than plague.


Development and initial psychometric properties of the Cannabidiol Outcome Expectancies Questionnaire (CBD-OEQ).
Cannabidiol (CBD), a nonpsychoactive cannabinoid, is used by many individuals to treat medical and mental health conditions, despite limited support for the efficacy of CBD for these conditions. Identification of CBD-related outcome expectancies (i.e., beliefs concerning the anticipated effects of CBD) could be useful in understanding the etiology and maintenance of CBD use and/or be useful in administration or clinical trial research. Although there are several measures of cannabis outcome expectancies, cannabis comprises several active compounds (e.g., tetrahydrocannabinol [THC], CBD). Thus, cannabis outcome expectancies may not reflect CBD-specific outcome expectancies. Yet, no known CBD-specific outcome expectancy measure exists. The present study used a three-phase, mixed-methods approach to develop and test the psychometric properties of the Cannabidiol Outcome Expectancy Questionnaire (CBD-OEQ). The CBD-OEQ assessed endorsement (i.e., how much an individual agrees/disagrees with an expected outcome) and desirability ratings (i.e., how desirable an expected outcome is). The initial item pool was administered to 600 adults who endorsed having heard of or using CBD products. Factor analyses supported a 60-item, six-factor structure. There was an initial support for internal consistency and convergent, discriminant, and incremental validity of the CBD-OEQ subscale scores in the present sample. Desirability ratings explained minimal additional variance in CBD variables for most subscales, but moderated the relationship between endorsement ratings and use behaviors for Global Negative Effects and No Effect subscales. The newly developed CBD-OEQ could be used as both a research and a clinical tool. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Posttranscriptional silencing of cytochrome P4501A1 (CYP1A1) during zebrafish (Danio rerio) development.
Induction patterns of cytochrome P4501A1 (CYP1A1), an early biochemical marker of exposure to the environmental toxicant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, or dioxin) were investigated during zebrafish (Danio rerio) development. A zebrafish CYP1A1 cDNA fragment was cloned and used to detect CYP1A1 mRNA in embryos exposed to TCDD (1 or 10 nM). Induction of CYP1A1 activity was dependent on age and state of hatch. CYP1A1 mRNA was observed by 15 hr postfertilization. CYP1A1 protein and monooxygenase activity were not detected until 3 days postfertilization and after hatch, as determined by Western immunoblot analysis and ethoxyresorufin O-deethylase (EROD) activity, respectively. In contrast to embryos, concomitant induction of mRNA and activity was detected in juvenile zebrafish (3 days posthatch) after 6 hr of TCDD exposure. Asynchronous induction of CYP1A1 mRNA and activity during development may be a general regulatory mechanism, as similar ontogenetic expression of this gene was demonstrated in mouse embryos. To our knowledge, this is the first report of CYP1A1 posttranscriptional silencing during embryogenesis. Our data suggest that TCDD-mediated induction of CYP1A1 activity is regulated differentially in developing and mature systems.


Prenatal tobacco prevention and cessation interventions for women in low- and middle-income countries.
Although the prevalence of tobacco use is decreasing in many high-income countries, it is increasing in many low- and middle-income countries. The health and economic burden of increasing tobacco use and dependence is predictable and will have devastating effects in countries with limited resources, particularly for vulnerable populations such as pregnant women. We sought to review effective tobacco prevention and intervention strategies for decreasing tobacco use and secondhand smoke exposure before and during pregnancy in high-, middle-, and low-income countries. We reviewed several types of interventions, including population-level efforts (increasing tobacco prices, implementing tobacco control policies), community interventions, clinical interventions, and pharmacological treatments. A second purpose of this report is to present findings of an international expert working group that was convened to review the evidence and to establish research priorities in the following areas: (a) preventing the uptake and reducing tobacco use among girls and women of reproductive age; and (b) reducing tobacco use and secondhand smoke exposure among pregnant women. The working group considered the evidence on existing interventions in terms of burden of disease, intervention impact, intervention costs, feasibility of integration into existing services, uniqueness of the contribution, and overall feasibility. Finally, we present the working group's recommendations for intervention research priorities.


Induction of ornithine decarboxylase in Reuber H35 rat hepatoma cells.
Stimuli known to induce tyrosine aminotransferase in H35 cells were tested relative to their ability to induce ornithine decarboxylase, the initial enzyme in the polyamine biosynthetic pathway. Dibutyryl cyclic AMP (0.5 mM), parachlorophenylthio-cyclic AMP (0.1 mM) and dexamethasone (1 muM) stimulated the activity of ornithine decarboxylase 7- to 8-fold by 5 hr of induction. There was a delay of 1 hr before any increase in enzyme activity was detectable. Insulin administered alone failed to significantly change ornithine decarboxylase activity. The ability of dibutyryl cyclic AMP to elevate ornithine decarboxylase activity was found to be concentration-dependent, and a dose-response relationship very similar to that for the induction of tyrosine aminotransferase by dibutyryl cyclic AMP was observed in these cells. The ability of various 8-substituted cyclic AMP analogues to increase the activity of ornithine decarboxylase was correlated with their ability to activate purified protein kinase.


Barriers and facilitators of successful weight loss during participation in behavioural weight management programmes: a protocol for a systematic review.
Behavioural weight management programmes are effective in assisting people with overweight or obesity to lose excess body weight. Yet, many still struggle to attain their weight loss goals in such programmes. Little is understood about the factors which impact success in these programmes. Synthesising this data will allow for theory to be developed on how to improve success in such programmes. The main aim of this review will be to extract and synthesise the barriers and facilitators of successful weight loss during participation of behavioural weight loss programmes in adults living with overweight and obesity. A systematic search of MEDLINE, Embase, PsycINFO, The Cochrane Library and CINAHL will be performed from inception onwards. Studies will also be sought by contacting experts in the field, reference and website searching. Studies will be eligible if the participants are adults living with obesity (population) undertaking or recently completed behavioural weight loss programmes (intervention) with the primary focus of weight loss (outcome). The primary outcomes will be amount of weight lost and information on barriers and/or facilitators to success. The secondary outcomes will be reasons or factors related to attrition and adherence and behaviour change techniques used in programmes. Two reviewers will screen citations and full-text data. Reviewer 1 will screen all, and reviewer 2 will screen a random 50% of articles. Data extraction will be completed by reviewer 1, and 10% will be checked by the research team. Potential conflicts will be resolved through discussion. Data will be synthesised and described narratively to show the characteristics of each study, levels of success and barriers and facilitators during programme participation. A thematic approach will be taken, and themes will be coded against the levels of the socioecological model. Quantitative data will be extracted and categorised according to these themes and presented alongside the qualitative data. Our findings can be used to inform how weight loss programmes can be improved to facilitate success in those at risk of failure. Results will be published in a peer-reviewed journal. SYSTEMATIC REVIEW REGISTRATION: ( PROSPERO CRD42019148158 ).


NXNL2 Promotes Colon Cancer Proliferation and Metastasis by Regulating AKT Pathway.
This study aimed to explore the role of nucleoredoxin-like 2 (NXNL2) in colon cancer (CC). The GEPIA and UALCAN databases were analyzed to explore genes involved in the prognosis of CC patients. DLD1 cells were treated with the DNA methylation inhibitor 5-azacitidine to validate the above findings. The methyltransferase DNMT (DNA methylation) was further knocked down by shRNA, then the expression of NXNL2 was assessed by qPCR. The role of NXNL2 on cell proliferation and metastasis was examined using corresponding assays. NXNL2 was found to exhibit the greatest impact on the prognosis of CC patients. High NXNL2 correlated with poor survival outcomes of CC. The expression of NXNL2 was regulated by DNA methylation. NXNL2 promoted CC cell proliferation and metastasis. Also, NXNL2 promoted the AKT pathway activity. In conclusion, NXNL2 could affect the cancer cell proliferation and metastasis, and has a poor survival prognosis in CC.


First Report of Anthracnose of Alocasia macrorrhiza Caused by Colletotrichum karstii in Guangdong, China.
Alocasia macrorrhiza (L.) Schott. (Araceae), native to South America, is a common, herbaceous perennial ornamental plant in tropical and subtropical areas (1). A severe leaf spot disease was observed on this plant in several places on the campus of authors' university in Guangzhou, Guangdong Province, China, in April 2013. Initial symptoms were water-soaked, dark green leaf spots. These small spots gradually expanded to 6- to 11-mm circular lesions. They were grayish-white in color with a yellow halo and many small, black, concentric dots were observed on them. Microscopic examination revealed that these small dots were acervuli, which were 100 to 300 μm in diameter, developing beneath the epidermis and becoming erumpent with age. By using routine tissue-isolation method and single-spore purification technique, four single-conidial isolates were obtained from each of four diseased leaves. These isolates formed a grayish-white colony with numerous pink spore masses on PDA at 28°C. Their mycelial radial growth rate was about 4.5 mm per day. Conidia were single-celled, hyaline, and cylindrical with an obtuse apex and protruding base; they were 12.7 to 14.2 × 4.8 to 5.9 μm in size. Conidial appressoria were irregular in shape, sepia to dark brown, solitary, and 6.9 to 8.5 × 4.6 to 5.9 μm. These morphological characteristics were consistent with the description of Colletotrichum karstii (2). The sequences of beta-tubulin gene (TUB2) and partial actin gene (ACT) of a representative isolate CAM1 were obtained by PCR amplification with primers BT2a/BT2b and ACT512F/ACT783R, respectively. These sequences were deposited in GenBank under the accession numbers of KF444947 and KF460435. BLAST searches showed a 99% homology with the TUB2 and ACT sequences of C. karstii (JX625209, KC843559). Therefore, the fungus isolated from A. macrorrhiza was identified as C. karstii by morphological and molecular characteristics. Pathogenicity tests were performed on 30-day-old plants of A. macrorrhiza grown in plastic pots (0.8 L) by spraying 15 ml conidial suspension (1 × 106 conidia ml-1) of this fungus onto each plant. The control plants were sprayed only with sterile distilled water. These plants then were placed in an intelligent artificial climate incubator with 12-h photoperiod and 100% relative humidity at 24 ± 1°C. Three replicates, each with five plants, were included in a test, and the test was repeated twice. Seven days after inoculation, the inoculated plants showed necrotic lesions on leaves similar to those observed on the campus, but no symptoms were observed on any non-inoculated controls. The same fungus C. karstii was re-isolated from the infected leaves. Although C. karstii is a well-known anthracnose pathogen on some plants belonging to family Orchidaceae (2), this is the first report of the same pathogen causing anthracnose on A. macrorrhiza in Guangdong, China. References: (1) S. Li et al. PLoS ONE 8(6):e66016, 2013. (2) Y. Yang et al. Cryptogr. Mycol. 32:229, 2011.


Population-based study on the seroprevalence of hepatitis A, B, and C virus infection in Amsterdam, 2004.
In order to enhance screening and preventive strategies, this study investigated the seroprevalence of hepatitis A, B, and C in the general adult urban population and in subgroups. In 2004, sera from 1,364 adult residents of Amsterdam were tested for viral markers. Sociodemographic characteristics were collected using a standardized questionnaire. For hepatitis A, 57.0% was immune. Of first-generation immigrants from Turkey and Morocco, 100% was immune. Of all Western persons and second-generation non-Western immigrants, approximately half was still susceptible. For hepatitis B, 9.9% had antibodies to hepatitis B core antigen (anti-HBc) and 0.4% had hepatitis B surface antigen. Anti-HBc seroprevalences were highest among first-generation immigrants from Surinam, Morocco, and Turkey, and correlated with age at the time of immigration, and among men with a sexual preference for men. Seroprevalence among second-generation immigrants was comparable to Western persons. The seroprevalence of hepatitis C virus antibodies was 0.6%. In conclusion, a country with overall low endemicity for viral hepatitis can show higher endemicity in urban regions, indicating the need for differentiated regional studies and prevention strategies. More prevention efforts in cities like Amsterdam are warranted, particularly for hepatitis A and B among second-generation immigrants, for hepatitis B among men with a sexual preference for men, and for hepatitis C. Active case finding strategies are needed for both hepatitis B and C.


[Endothelial vesicles as a transport system in the blood-brain barrier. Morphometric study during development].
The vesicles and vacuoles of the endothelia, morphological expression of endocytosis and transendothelial transport, are quite absent in the mature neural endothelia. In order to study the temporal sequence of the vesicle and vacuole modifications during the blood brain barrier (bbb) setting up, the extent of these structures was morphometrically analyzed on electron micrographs of neural microvessels in the optic tectum of 8, 14, and 17 day chick embryos, fixed after an intracardial injection of the permeability marker horseradish peroxidase. During the development, endocytosis and transendothelial transport change, since a statistically significant reduction of both vesicles and vacuoles was recorded at the 17th incubation day. The temporal coincidence between decrease of endocytosis-transport processes and appearance of astrocytic endfeet close to the vessel wall, suggests that the glial cells might control, besides the tight junction formation, the expression of other properties of the bbb-provided endothelia.


Office-based dynamic imaging of vocal cords in awake patients with swept-source optical coherence tomography.
Optical coherence tomography (OCT) is an evolving noninvasive imaging modality that has been used to image the human larynx during surgical endoscopy. The design of a long gradient index (GRIN) lens-based probe capable of capturing images of the human larynx by use of swept-source OCT during a typical office-based laryngoscopy examination is presented. In vivo OCT imaging of the human larynx is demonstrated with a rate of 40 frames per second. Dynamic vibration of the vocal folds is recorded to provide not only high-resolution cross-sectional tissue structures but also vibration parameters, such as the vibration frequency and magnitude of the vocal cords, which provides important information for clinical diagnosis and treatment, as well as fundamental research of the voice itself. Office-based OCT is a promising imaging modality to study the larynx for physicians in otolaryngology.


Changes in physician attitudes toward limiting care of critically ill patients.
To determine whether physician attitudes toward decision making in the care of critically ill patients have changed, a survey of physicians was conducted in 1981 and repeated in 1988. Physicians in 1988 were more comfortable discussing "do-not-resuscitate" options with patients and were more likely to allow a critically ill patient to die if the patient so requested. Most physicians in both surveys believe that treatment costs should not play a role in medical decisions. Trainees in 1988 were more aggressive in their management of case studies than were faculty in 1988 or trainees in 1981. While in both years the most important factors in the decision to treat aggressively were a patient's expressed desire to live or die and the amount of patient suffering, physicians in 1988 ranked malpractice concerns as a more important determinant in their decision process compared with physicians in 1981. Significant changes in physician attitudes toward the care of critically ill patients have occurred during this decade.


Anicteric Gallbladder Rupture with Elevated Bile Acids in Abdominal Effusion in a Dog with Cholecystitis.
Anicteric gallbladder rupture has been rarely described in veterinary medicine, and, generally, it has been related to gallbladder wall necrosis secondary to gallbladder mucocele. A 5 yr old, male, neutered Labrador retriever presented for acute onset anorexia, lethargy, and vomiting. Cholecystitis was diagnosed based on the ultrasonographic findings and bactibilia, and, consequently, medical treatment was established. Despite improvement of the patient, a focal ultrasound of the hepatobiliary tract was performed 72 hr after admission for reassessment, revealing gallbladder wall thickening and abdominal effusion. Intracellular bacteria were present in nondegenerated neutrophils, and the effusion was categorized as septic exudate, compatible with septic peritonitis. Exploratory laparotomy confirmed an anicteric gallbladder rupture potentially secondary to cholecystitis and/or previous cholecystocentesis. The patient was not icteric the day of the surgery, serum bilirubin was within normal limits, abdominal fluid bilirubin concentration was below that of serum, and no bile pigment was detected; however, bile acids were significantly higher in the abdominal effusion compared with the serum concentration. This case describes an anicteric gallbladder rupture in a dog with concomitant cholecystitis and raises the question about the sensitivity of bile acid evaluation as a tool for diagnosis of gallbladder rupture and bile peritonitis in dogs.


Increase in random component of heart rate variability coinciding with developmental and degenerative stages of life.
To adapt to a new environment or situation, biological systems explore the most convenient state while moving between attractors by the force of random fluctuation. From this concept, the random component in physiological signals is assumed to increase during developmental and degenerative stages of life. To examine this hypothesis, we measured the age-dependent changes in the random component of heart rate variability (HRV) in 24-h electrocardiography (ECG) big data and in patients with a developmental disorder (DD). We measured separately regulated and random components of HRV with autoregressive (AR) model fitting, by which the ratio of random component as the fractional variance of AR residual time series. From the ALLSTAR database of about 304 000 ambulatory 24-h ECGs, we randomly extracted the data of 1930 men and 1987 women uniformly for all ages from 0 to 100 years old (100 cases per 5-year strata for each sex). Data were also obtained from male pediatric patients with DD (age 10-15 years). While the variance of the regulated component of HRV increased from age 0 to 20, decreased with age until 40, and reached a plateau in both sexes, the ratio of the random component was high at birth, decreased with age until 35 in men and 30 in women, and increased again after 75 in men and 85 in women (P < 0.0001 for all). In patients with a DD, the ratio of the random component was significantly lower than that in age-and-sex matched subjects in the database. We found that the ratio of the random component of HRV is increased during developmental and degenerative stages of life and that it may be reduced in DD patients during their development.


Interaction of tomudex with radiation in vitro and in vivo.
The potential of the thymidylate synthase inhibitor, Tomudex to interact with ionizing radiation was assessed in vitro and in vivo in comparison with 5-fluorouracil. A concentration of 1 microM Tomudex decreased the shoulder of the radiation survival curves for normally oxygenated and hypoxic human HT-29 colon carcinoma cells and human SCC-25 head and neck squamous carcinoma cells, resulting in enhancement ratios of 10 and 2.8 for normally oxygenated and hypoxic HT-29 cells at 5 Gray, respectively, and enhancement ratios of 19.5 and 2.7 for normally oxygenated and hypoxic SCC-25 cell at 5 Gray, respectively. Two schedules of Tomudex administered to animals bearing the Lewis lung carcinoma resulted in additive tumor growth delay with the fractionated radiation therapy. In nude mice bearing the HT-29 colon carcinoma grown as a xenograft, administration of Tomudex daily for 5 days on a 1 or 2-week schedule resulted in increased tumor growth delay along with fractionated radiation therapy on the same schedules. However, administration of Tomudex intermittently on a 2-week schedule appeared to be more interactive with daily fractionated radiation therapy on the 2-week schedule. In each assay, the results obtained with Tomudex were equal to or exceeded those obtained with 5-fluorouracil. These findings indicate that clinical trial of Tomudex along with fractionated radiation therapy is warranted.


Applying Rasch analysis to evaluate measurement equivalence of different administration formats of the Activity Limitation scale of the Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR).
Electronic formats of patient-reported outcome (PRO) measures are now routinely used in clinical research studies. When changing from a validated paper and pen to electronic administration it is necessary to establish their equivalence. This study reports on the value of Rasch analysis in this process. Three groups of US pulmonary hypertension (PH) patients participated. The first completed an electronic version of the CAMPHOR Activity Limitation scale (e-sample) and this was compared with two pen and paper administrated samples (pp1 and pp2). The three databases were combined and analysed for fit to the Rasch model. Equivalence was evaluated by differential item functioning (DIF) analyses. The three datasets were matched randomly in terms of sample size (n = 147). Mean age (years) and percentage of male respondents were as follows: e-sample (51.7, 16.0 %); pp1 (50.0, 14.0 %); pp2 (55.5, 40.4 %). The combined dataset achieved fit to the Rasch model. Two items showed evidence of borderline DIF. Further analyses showed the inclusion of these items had little impact on Rasch estimates indicating the DIF identified was unimportant. Differences between the performance of the electronic and pen and paper administrations of the CAMPHOR Activity Limitation scale were minor. The results were successful in showing how the Rasch model can be used to determine the equivalence of alternative formats of PRO measures.


An Outsourced Health-enhancing Physical Activity Program for People with Rheumatoid Arthritis: Study of the Maintenance Phase.
To describe changes of health-enhancing physical activity (HEPA), health perception, and functioning during the second year of a 2-year support program, determine aspects of adherence and response, and describe perceptions of the program. Out of 220 individuals with rheumatoid arthritis (RA), 177 participated in the followup. Group support, strength training, and moderate-intensity aerobic activity were encouraged. Data collection included HEPA, perceived health, functioning, and perceptions of the program. Participants with unchanged/improved general health perception and at least 2 of aerobic capacity, grip strength, or timed standing were considered responders. Current and maintained HEPA decreased from 82% to 75% (p = 0.0141) and from 41% to 27% (p < 0.0001) during the second year. Minor declines in quality of life and activity limitation occurred (p = 0.0395 and 0.0038, respectively), while outcome expectations for benefits of physical activity increased (p = 0.0010 and 0.0186) and waist circumference tapered off (p = 0.0070). Strength training was performed on average 41 and 35 times among responders (n = 54) and nonresponders (n = 105), respectively (p = 0.2708); HEPA 194 and 171 days, respectively (p = 0.0828); and support group meetings 12 and 10 times, respectively (p = 0.0943). Strength training, aerobic activity, and short text message reminders were perceived as most valuable; step registration and the self-monitoring walk tests were less appreciated. About one-fourth of the originally sedentary individuals with RA sustained their new HEPA behaviors after 2 years and most improvements of health and functioning were sustained. Structured use of behavior change techniques and a second year to support maintenance with a reduced program might help patients with RA to sustain HEPA behavior.


DNA-mediated charge transport in redox sensing and signaling.
The transport of charge through the DNA base-pair stack offers a route to carry out redox chemistry at a distance. Here we describe characteristics of this chemistry that have been elucidated and how this chemistry may be utilized within the cell. The shallow distance dependence associated with these redox reactions permits DNA-mediated signaling over long molecular distances in the genome and facilitates the activation of redox-sensitive transcription factors globally in response to oxidative stress. The long-range funneling of oxidative damage to sites of low oxidation potential in the genome also may provide a means of protection within the cell. Furthermore, the sensitivity of DNA charge transport to perturbations in base-pair stacking, as may arise with base lesions and mismatches, may be used as a route to scan the genome for damage as a first step in DNA repair. Thus, the ability of double-helical DNA in mediating redox chemistry at a distance provides a natural mechanism for redox sensing and signaling in the genome.


Beyond HMOs: trends in employer direct contracting.
The California Public Employees' Retirement System (CalPERS) is exploring the possibility of contracting directly with providers to furnish healthcare services to its members. This move may signal a trend among employers to pursue direct-contracting opportunities. The direct-contracting experience of Minnesota's Buyers Health Care Action Group (BHCAG) high-lights how such arrangements may be structured. Direct contracting may not yet exist in every market. Nonetheless, providers that proactively position themselves to meet employer expectations should be able to strengthen their market position and gain leverage in contracting with managed care organizations.


Brachydactyly type A1 with abnormal menisci and scoliosis in three generations.
We report a three-generation family in which four members had brachydactyly type A1, degenerative arthritis of the knee as a complication of abnormal menisci, and variable scoliosis. Nine of the 15 individuals in the two generations preceding the proband had brachydactyly. Three of these nine had degenerative arthritis of the knee including the proband's father who had meniscal degeneration with tears. One other had radiologically confirmed discoid menisci. Of those with brachydactyly, five also had scoliosis. Although autosomal dominant inheritance of brachydactyly A1 and discoid menisci have been reported separately, cosegregation of these features in one family has not previously been described and seems to comprise a unique autosomal dominant condition. The combination of brachydactyly, meniscal abnormalities including discoid meniscus, and scoliosis suggests that this disorder represents a new osteochondrodysplasia syndrome.


[The study of soy isoflavone metabolism in patients with cardiovascular diseases].
The investigation of influent of antiatherosclerotic diets with various component of phytoestrogens on clinical and metabolic parameters in patients with ischemic heart disease and hypertension. Definition of quantity isoflavones in soy protein products, in diets and in urine patients before and after treatment.


Microvascular architecture of the filiform papillae in primates and insectivores.
The microvascular architecture of filiform papillae was investigated under a scanning electron microscope in man, Japanese monkeys, common squirrel monkeys, common marmosets, common tree shrews, large Japanese moles and dwarf shrews utilizing microvascular corrosion casts. Filiform papillae were circularly arranged in primates, and each of them was supplied by a hairpin capillary loop. These papillae sometimes were aggregated. The filiform papillae of Japanese monkeys exhibited markedly locational differences on the lingual dorsum and were supplied by circularly arranged capillary loops or by an intrapapillary capillary network. Small filiform papillae were located on an epithelial eminence in the lingual radix, each of them supplied by a low and simple hairpin capillary loop. The aggregated filiform papillae of common squirrel monkeys were less frequent without any locational differences. Low filiform papillae of common marmosets and tree shrews were simpler in form, being arranged in a circle and supplied by a simple hairpin capillary loop. The filiform papillae of insectivores were not arranged in a circle. The filiform papillae of dwarf shrews were supplied by an incomplete capillary ring without a loop. With respect to species differences, the circularly arranged capillary loops in man were most complicated and highly developed. Microvascular architecture of the filiform papillae of insectivores was much simpler, different from those observed in primates.


Investigating post-mild traumatic brain injury neuromuscular function and musculoskeletal injury risk: A protocol for a prospective, observational, case-controlled study in service members and active individuals.
Musculoskeletal injury (MSKI) risk is increased following mild traumatic brain injury (mTBI). Increased MSKI risk is present up to 2 years following post-mTBI return-to-duty/activity relative to both non-mTBI peers and to their pre-mTBI selves across a range of populations, including military service members, and professional, college and high school athletes. Despite the well documented increased post-mTBI MSKI risk, the underlying neuromuscular mechanisms contributing to this increased risk have yet to be definitively determined. A number of potential mechanisms have been suggested (eg, aberrant kinematics, dynamic balance impairments, lower voluntary muscle activation), but none have been confirmed with a comprehensive, prospective study. This study aims to: (1) elucidate the neuromuscular control mechanisms following mTBI that contribute to increased MSKI risk, and (2) prospectively track patient outcomes (up to 12 months; MSKI occurrences and patient-reported outcomes (PRO)). This is a multicentre prospective, case-matched control observational study to identify deficiencies in neuromuscular function following mTBI that may contribute to increased MSKI risk. Participants (aim to recruit 148, complete data collection on 124) will be classified into two cohorts; mTBI and control. All participants will undergo longitudinal (initial, 6 weeks post-initial, 12 weeks post-initial) comprehensive three-dimensional biomechanical (jump-landing; single leg hop; cut; gait), neuromuscular (interpolated twitch technique, muscular ramp contraction) and sensory (joint repositioning; light touch sensation) assessments to elucidate the underlying neuromuscular control mechanisms post-mTBI that may contribute to increased MSKI. Occurrences of MSKI and PROs (National Institutes of Health Patient-Reported Outcome Measurement Information System: Physical Function, Pain Interference, Depression, Anxiety; Brief Resilience Scale; Tampa Scale of Kinesiophobia), will be tracked monthly (up to 1 year) via electronic data capture platforms. The study received approval from the Walter Reed National Military Medical Center Institutional Review Board. Results will be made available to the associated funding agency and other researchers via conference proceedings and journal articles. NCT05122728.


Cardiovascular effects of meperidine-N2O anesthesia before and after pancuronium.
The cardiovascular effects of 2 and 3 mg/kg of meperidine plus 60 to 67% N2O in O2 on cardiovascular dynamics in man were measured before and after the administration of 0.08 mg/kg of IV pancuronium. N2O and 2 mg/kg of meperidine did not change heart rate (HR) but produced a marked reduction (-49%) in cardiac output (QT) plus significant decreases in stroke volume (SV) and blood pressure (BP) and an increase in peripheral arterial resistance (PVR). Additional meperidine did not further alter any of the variables; however, surgical stimulation caused significant increases in HR, BP, and PVR. SV and QT were not significantly changed by surgical stimulation and were still markedly depressed when compared to control values. Pancuronium produced marked increases in HR, SV, QT, and BP and a reduction in PVR. These changes were maximal 4 to 8 minutes after pancuronium and returned toward pre-pancuronium values thereafter. These data demonstrate that N2O-meperidine anesthesia results in a moderate reduction in BP but a marked depression in QT. The findings also indicate that pancuronium reverses the cardiovascular depression produced by N2O-meperidine and is therefore, a desirable muscle relaxant when the above technic is employed.


Knowledge translation and patient safety: the Canadian Adverse Events Study.
The Canadian Adverse Events Study was the first national study of adverse events in Canadian hospitals. Learning from the controversy surrounding similar studies in other countries, the team engaged in extensive knowledge translation activities throughout the life of the project. Using meetings, Web-based communication and other tools, the team successfully prepared most Canadian stakeholders for the study's release, allowing them to develop anticipatory patient safety initiatives. However, upon publication of the study, the policy spotlight quickly shifted to other issues, and the long-term commitment needed to create safer healthcare is still uncertain.


Heterozygous abnormal fibrinogen Osaka III with the replacement of gamma arginine-275 by histidine has an apparently higher molecular weight gamma-chain variant.
Congenitally abnormal fibrinogen Osaka III with the replacement of gamma Arg-275 by His was found in a 38-year-old female with no bleeding or thrombotic tendency. Release of fibrinopeptide(s) by thrombin or reptilase was normal, but her thrombin or reptilase time in the absence of calcium was markedly prolonged and the polymerization of preformed fibrin monomer which was prepared by the treatment of fibrinogen with thrombin or reptilase was also markedly defective. Propositus' fibrinogen had normal crosslinking abilities of alpha- and gamma-chains. Analysis of fibrinogen chains on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) in the system of Laemmli only revealed the presence of abnormal gamma-chain with an apparently higher molecular weight, the presence of which was more clearly detected with SDS-PAGE of fibrin monomer obtained by thrombin treatment. Purified fragment D1 of fibrinogen Osaka III also seemed to contain an apparently higher molecular weight fragment D1 gamma remnant on Laemmli gels, which was digested faster than the normal control by plasmin in the presence of [ethylenebis(oxyethylenenitrilo)]tetraacetic acid (EGTA).


Application of non-covalently solid-phase bound catalysts.
Supported catalysts have become valuable tools for simplified product isolation and catalyst recycling. The common method is covalent attachment to a solid support. An alternative strategy is to immobilize catalysts by non-covalent bonding through hydrogen bridges, ionic, hydrophobic or fluorous interactions. Compared to covalent attachment, such non-covalent approaches increase the flexibility in the choice of the support-material, reaction conditions and work-up strategies. Numerous catalytic reactions employing one of these non-covalent fixation strategies have meanwhile appeared in the literature.


Anaerobic threshold using sweat lactate sensor under hypoxia.
We aimed to investigate the reliability and validity of sweat lactate threshold (sLT) measurement based on the real-time monitoring of the transition in sweat lactate levels (sLA) under hypoxic exercise. In this cross-sectional study, 20 healthy participants who underwent exercise tests using respiratory gas analysis under hypoxia (fraction of inspired oxygen [FiO2], 15.4 ± 0.8%) in addition to normoxia (FiO2, 20.9%) were included; we simultaneously monitored sLA transition using a wearable lactate sensor. The initial significant elevation in sLA over the baseline was defined as sLT. Under hypoxia, real-time dynamic changes in sLA were successfully visualized, including a rapid, continual rise until volitionary exhaustion and a progressive reduction in the recovery phase. High intra- and inter-evaluator reliability was demonstrated for sLT's repeat determinations (0.782 [0.607-0.898] and 0.933 [0.841-0.973]) as intraclass correlation coefficients [95% confidence interval]. sLT correlated with ventilatory threshold (VT) (r = 0.70, p < 0.01). A strong agreement was found in the Bland-Altman plot (mean difference/mean average time: - 15.5/550.8 s) under hypoxia. Our wearable device enabled continuous and real-time lactate assessment in sweat under hypoxic conditions in healthy participants with high reliability and validity, providing additional information to detect anaerobic thresholds in hypoxic conditions.


Medicare program; schedule of limits for skilled nursing facility inpatient routine service costs--HCFA. Final notice of schedule of limits.
This notice sets forth a revised schedule of limits on skilled nursing facility inpatient routine service costs that are paid for under Medicare. This schedule applies to cost reporting periods beginning on or after October 1, 1987.


Strategies for the Treatment of Infantile Soft Tissue Sarcomas With BCOR Alterations.
BCOR alterations are described in ultra-rare infantile soft tissue sarcomas including primitive myxoid mesenchymal tumor of infancy and undifferentiated round cell sarcoma (URCS). Previous reports often describe dismal outcomes. Thus, we undertook a retrospective, multi-institutional study of infants with BCOR -rearranged soft tissue sarcomas. Nine patients aged 6 weeks to 15 months were identified. One tumor carried a BCOR :: CCNB3 fusion, whereas 7 tumors harbored internal tandem duplication of BCOR , including 4 cases classified as primitive myxoid mesenchymal tumor of infancy, 1 case as URCS, and 2 cases characterized by a "hybrid morphology" in our evaluation. Four patients underwent upfront surgery with residual disease that progressed locally after a median of 2.5 months. Locoregional recurrences were observed in hybrid patients, and the URCS case recurred with brain metastases. Complete radiographic responses after chemotherapy were achieved in patients treated with vincristine/doxorubicin/cyclophosphamide alternating with ifosfamide/etoposide, vincristine/doxorubicin/cyclophosphamide alternating with cyclophosphamide/etoposide (regimen I), and ifosfamide/carboplatin/etoposide. Seven patients received radiotherapy. With a median of 23.5 months off therapy, 8 patients are with no evidence of disease. In our study, observation was inadequate for the management of untreated postsurgical residual disease. Tumors demonstrated chemosensitivity with anthracycline-based regimens and ifosfamide/carboplatin/etoposide. Radiotherapy was required to achieve durable response in most patients.


Randomized controlled trial of salbutamol aerosol therapy via metered dose inhaler-spacer vs. jet nebulizer in young children with wheezing.
The jet nebulizer is a common device used for administering aerosol medication in young children. However, compared to a metered dose inhaler-spacer (MDI-spacer), it takes more time and personnel. This study aimed to compare the efficacy of salbutamol aerosol therapy given via these two devices in young wheezing children. A prospective randomized, double-blind, placebo-controlled trial was performed in children up to 5 years old who had acute wheezing and were admitted to the Department of Pediatrics, King Chulalongkorn Memorial Hospital. Patients were randomly divided into two groups. The first group received 2 puffs of placebo via MDI-spacer, followed by 0.15 mg/kg salbutamol respiratory solution via jet nebulizer. The second group received 2 puffs (100 microg/puff) of salbutamol via MDI-spacer, followed by placebo via jet nebulizer. Clinical scores and tidal breathing pulmonary function test were evaluated before and after treatment. Pulmonary function parameters included those derived from flow volume loops (volume to peak tidal expiratory flow over total expiratory volume, V(PTEF)/V(E); time to peak tidal expiratory flow over total expiratory time, T(PTEF)/T(E); and ratio of tidal expiratory flow at 25% remaining expiration to peak expiratory flow, 25/PF), compliance (Crs), and resistance (Rrs) of the respiratory system. The efficacy of both methods was compared by using analysis of covariance. Forty-seven wheezing children were studied (24 received salbutamol via MDI-spacer, and 23 received it via jet nebulizer). There was no statistical difference between the two groups regarding clinical scores and all pulmonary function parameters. However, heart rate was significantly increased after treatment in the jet nebulizer group when compared to those in the MDI-spacer group (P = 0.004). In conclusion, the efficacy of salbutamol aerosol therapy via MDI-spacer compared to jet nebulizer in young wheezing children was not different in terms of clinical score and postbronchodilator pulmonary function parameters. However, salbutamol aerosol therapy via jet nebulizer significantly increased the heart rate when compared to the MDI-spacer.


Signature Arsenic Detoxification Pathways in Halomonas sp. Strain GFAJ-1.
Since the original report that Halomonas sp. strain GFAJ-1 was capable of using arsenic instead of phosphorus to sustain growth, additional studies have been conducted, and GFAJ-1 is now considered a highly arsenic-resistant but phosphorus-dependent bacterium. However, the mechanisms supporting the extreme arsenic resistance of the GFAJ-1 strain remain unknown. In this study, we show that GFAJ-1 has multiple distinct arsenic resistance mechanisms. It lacks the genes to reduce arsenate, which is the essential step in the well-characterized resistance mechanism of arsenate reduction coupled to arsenite extrusion. Instead, GFAJ-1 has two arsenic resistance operons, arsH1-acr3-2-arsH2 and mfs1-mfs2-gapdh, enabling tolerance to high levels of arsenate. mfs2 and gapdh encode proteins homologous to Pseudomonas aeruginosa ArsJ and glyceraldehyde-3-phosphate dehydrogenase (GAPDH), respectively, which constitute the equivalent of an As(V) efflux system to catalyze the transformation of inorganic arsenate to pentavalent organoarsenical 1-arseno-3-phosphoglycerate and its subsequent extrusion. Surprisingly, the arsH1-acr3-2-arsH2 operon seems to consist of typical arsenite resistance genes, but this operon is sufficient to confer both arsenite and arsenate resistance on Escherichia coli AW3110 even in the absence of arsenate reductase, suggesting a novel pathway of arsenic detoxification. The simultaneous occurrence of these two unusual detoxification mechanisms enables the adaptation of strain GFAJ-1 to the particularly arsenic-rich environment of Mono Lake.IMPORTANCEHalomonas sp. strain GFAJ-1 was previously reported to use arsenic as a substitute for phosphorus to sustain life under phosphate-limited conditions. Although this claim was later undermined by several groups, how GFAJ-1 can thrive in environments with high arsenic concentrations remains unclear. Here, we determined that this ability can be attributed to the possession of two arsenic detoxification operons, arsH1-acr3-2-arsH2 and mfs1-mfs2-gapdhmfs2 and gapdh encode proteins homologous to ArsJ and GAPDH in Pseudomonas aeruginosa; these proteins create an arsenate efflux pathway to reduce cellular arsenate accumulation. Interestingly, the combination of acr3-2 with either arsH gene was sufficient to confer resistance to both arsenite and arsenate in E. coli AW3110, even in the absence of arsenate reductase, suggesting a new strategy for bacterial arsenic detoxification. This study concludes that the survival of GFAJ-1 in high arsenic concentrations is attributable to the cooccurrence of these two unusual arsenic detoxification mechanisms.


Learning-based meta-algorithm for MRI brain extraction.
Multiple-segmentation-and-fusion method has been widely used for brain extraction, tissue segmentation, and region of interest (ROI) localization. However, such studies are hindered in practice by their computational complexity, mainly coming from the steps of template selection and template-to-subject nonlinear registration. In this study, we address these two issues and propose a novel learning-based meta-algorithm for MRI brain extraction. Specifically, we first use exemplars to represent the entire template library, and assign the most similar exemplar to the test subject. Second, a meta-algorithm combining two existing brain extraction algorithms (BET and BSE) is proposed to conduct multiple extractions directly on test subject. Effective parameter settings for the meta-algorithm are learned from the training data and propagated to subject through exemplars. We further develop a level-set based fusion method to combine multiple candidate extractions together with a closed smooth surface, for obtaining the final result. Experimental results show that, with only a small portion of subjects for training, the proposed method is able to produce more accurate and robust brain extraction results, at Jaccard Index of 0.956 +/- 0.010 on total 340 subjects under 6-fold cross validation, compared to those by the BET and BSE even using their best parameter combinations.


(4-Aminopyridine)-PLGA-PEG as a Novel Thermosensitive and Locally Injectable Treatment for Acute Peripheral Nerve Injury.
Traumatic peripheral nerve injury (TPNI) represents a major medical problem that results in loss of motor and sensory function, and in severe cases, limb paralysis and amputation. To date, there are no effective treatments beyond surgery in selective cases. In repurposing studies, we found that daily systemic administration of the FDA-approved drug 4-aminopyridine (4-AP) enhanced functional recovery after acute peripheral nerve injury. This study was aimed at constructing a novel local delivery system of 4-AP using thermogelling polymers. We optimized a thermosensitive (4-AP)-poly(lactide-co-glycolide)-b-poly(ethylene glycol)-b-poly(lactide-co-glycolide) (PLGA-PEG-PLGA) block copolymer formulation. (4-AP)-PLGA-PEG exhibited controlled release of 4-AP both in vitro and in vivo for approximately 3 weeks, with clinically relevant safe serum levels in animals. Rheological investigation showed that (4-AP)-PLGA-PEG underwent a solution to gel transition at 32 °C, a physiologically relevant temperature, allowing us to administer it to an injured limb while subsequently forming an in situ gel. A single local administration of (4-AP)-PLGA-PEG remarkably enhanced motor and sensory functional recovery on post-sciatic nerve crush injury days 1, 3, 7, 14, and 21. Moreover, immunohistochemical studies of injured nerves treated with (4-AP)-PLGA-PEG demonstrated an increased expression of neurofilament heavy chain (NF-H) and myelin protein zero (MPZ) proteins, two major markers of nerve regeneration. These findings demonstrate that (4-AP)-PLGA-PEG may be a promising long-acting local therapeutic agent in TPNI, for which no pharmacologic treatment exists.


Improper orientational ordering regime and tricritical behavior in a lyotropic liquid crystal.
Optical microscopy, deuteron quadrupolar NMR, x-ray diffraction, and electrical conductivity techniques have been used to map the phase diagram and to measure the nematic order parameter variation (S) in ternary mixtures of pentadecafluorooctanoate acid ammonium salt (APFO), heavy water (D2O), and ammonium chloride (NH4Cl). A phenomenological model with an isotropic parent phase and a single primary segregation order parameter is elaborated on to describe in consistent terms the linear dependence of S(T) through the whole nematic stability region as well as the existence of a tricritical point at the nematic-to-lamellar phase transition line.


Solid-Phase Synthesis of Azole-Comprising Peptidomimetics and Coordination of a Designed Analog to Zn2.
Peptidomimetics that can coordinate transition metals have a variety of potential applications as catalysts, sensors, or materials. A new modular peptidomimetic scaffold, the "azole peptoid", is introduced here. We report methods for the solid-phase synthesis of eleven examples of trimeric N-substituted oligoamides that include oxazole- or thiazole-functionalized backbones. The products prepared comprise a diversity of functionality, including a metal-coordinating terpyridine group. The modular synthetic approach enables ready preparation of analogs for specific applications. To highlight a potential use of this new synthetic scaffold, a trimeric azole peptoid functionalized with a terpyridine residue was prepared and studied. The characteristic 2:1 ligand:metal binding of this terpyridine-functionalized azole peptoid to Zn2+ in aqueous solution was observed. These studies introduce azole peptoids as a useful class of biomimetic molecules for further study and application.


Comparison of the 308-nm excimer laser and a 308-nm excimer lamp with 311-nm narrowband ultraviolet B in the treatment of psoriasis.
Psoriasis is a chronic, genetically determined inflammatory disease, characterized by an immunomediated pathogenesis, which affects approximately 1-3% of the population. Various modalities have been used for psoriasis treatment, including ultraviolet (UV) radiation. Narrowband UVB (311 nm) phototherapy is a well-established, widely used and highly efficient treatment for psoriasis, but a big disadvantage is that large areas of unaffected skin are irradiated along with the psoriatic lesions. This investigation evaluates a 308-nm excimer laser and a 308-nm excimer lamp in comparison with 311-nm narrowband UVB in the treatment of patch psoriasis by using two different dose-increase schemes. Fifteen patients with plaque psoriasis were enrolled in the study (first regime). Three different psoriatic lesions were treated with the 308-nm excimer laser, the 308-nm excimer lamp or 311-nm narrowband UVB three times per week. UVB doses were increased slowly and stepwise (1, 1, 2, 2, 3, 3, ...multiple MEDs). Sixteen patients were enrolled in the second regime. Two plaques were treated with the 308-nm excimer laser or with the 308-nm lamp with an accelerated scheme (2, 2, 4, 4, 6, 6, ...multiple MEDs) three times per week. We increased the UVB doses every second treatment (first and second regime) during the whole treatment. If blistering occurred, the blistered plaque was not treated on the next scheduled treatment. At every third visit and 1, 2 and 4 months after the last treatment a Psoriasis Severity Index (PSI) score was assigned in both regimes. Using Friedman analysis, the PSI scores did not show a statistically significant difference (P > 0.05) comparing 308-nm laser therapy, 308-nm lamp therapy and 311-nm narrowband therapy after 10 weeks in the first regime. The mean number of treatments to achieve clearance was 24. With the accelerated scheme, clearance could be achieved with fewer treatments and with half the cumulative dose of the first regime. Nevertheless, the side-effects such as blistering and crusting were also increased. Both 308-nm light sources can clear patch psoriasis in a similar manner to standard phototherapy, with the advantage of the ability to treat exclusively the affected skin and with a reduced cumulative dose, thus perhaps reducing the long-term risk of carcinogenicity.


Dynamics of cellular HIV-1 DNA levels over 144 weeks of darunavir/ritonavir monotherapy versus triple therapy in the MONET trial.
In patients receiving combination antiretroviral therapy (ART), switching to monotherapy with ritonavir-boosted darunavir (DRV/r) can maintain plasma HIV-1 RNA suppression with no treatment-emergent drug resistance; effects on cellular HIV-1 DNA burden are less well characterized. In MONET, patients on stable combination ART for at least 6 months with plasma HIV-1 RNA <50 copies/mL and no history of virologic failure switched to DRV/r 800/100 mg once daily, either alone (n = 127) or with 2 nucleos(t)ide reverse transcriptase inhibitors (NRTIs) (n = 129). In a representative subset of 146 patients, total HIV-1 DNA load in peripheral blood mononuclear cells (PBMC) was tested retrospectively at baseline, week 48, week 96, and week 144. Mean HIV-1 DNA levels at baseline vs week 144 were 2.50 vs 2.49 log10 copies/106 PBMC in the monotherapy arm and 2.59 vs 2.61 log10 copies/106 PBMC in the triple therapy arm, with mean (median) changes of -0.05 (-0.03) and +0.03 (+0.01) log10 copies/106 PBMC in the 2 arms, respectively. Overall baseline HIV-1 DNA levels were higher in patients with nadir CD4 counts <200 cell/µL (P<.05) and in patients who over 144 weeks experienced at least 1 HIV-1 RNA measurement >50 copies/mL (P < .05). In this substudy of the MONET trial, HIV-1 DNA levels remained stable during 144 weeks of either DRV/r monotherapy or triple therapy with DRV/r + 2 NRTIs. In both treatment arms, baseline HIV-1 DNA levels were predicted by the nadir CD4 cell count and predictive of plasma HIV-1 RNA detection during follow-up.


Aerobic Barley Mg-protoporphyrin IX Monomethyl Ester Cyclase is Powered by Electrons from Ferredoxin.
Chlorophyll is the light-harvesting molecule central to the process of photosynthesis. Chlorophyll is synthesized through 15 enzymatic steps. Most of the reactions have been characterized using recombinant proteins. One exception is the formation of the isocyclic E-ring characteristic of chlorophylls. This reaction is catalyzed by the Mg-protoporphyrin IX monomethyl ester cyclase encoded by Xantha-l in barley (Hordeum vulgare L.). The Xantha-l gene product (XanL) is a membrane-bound diiron monooxygenase, which requires additional soluble and membrane-bound components for its activity. XanL has so far been impossible to produce as an active recombinant protein for in vitro assays, which is required for deeper biochemical and structural analyses. In the present work, we performed cyclase assays with soluble and membrane-bound fractions of barley etioplasts. Addition of antibodies raised against ferredoxin or ferredoxin-NADPH oxidoreductase (FNR) inhibited assays, strongly suggesting that reducing electrons for the cyclase reaction involves ferredoxin and FNR. We further developed a completely recombinant cyclase assay. Expression of active XanL required co-expression with an additional protein, Ycf54. In vitro cyclase activity was obtained with recombinant XanL in combination with ferredoxin and FNR. Our experiment demonstrates that the cyclase is a ferredoxin-dependent enzyme. Ferredoxin is part of the photosynthetic electron-transport chain, which suggests that the cyclase reaction might be connected to photosynthesis under light conditions.


Natural language processing in the molecular imaging domain.
Molecular imaging represents the intersection between imaging and genomic sciences. There has been a surge in research literature and information in both sciences. Information contained within molecular imaging literature could be used to 1) link to genomic and imaging information resources and 2) to organize and index images. This research focuses on the adaptation, evaluation, and application of BioMedLEE, a natural language processing system (NLP), in the automated extraction of information from molecular imaging abstracts.


Hypoglycemia and Cardiovascular Disease: Lessons from Outcome Studies.
Severe hypoglycemia is recognized to be one of the strongest predictors of macrovascular events, adverse clinical outcomes, and mortality in patients with type 2 diabetes. Large clinical trials have reported an increased hazard ratio for all-cause mortality and cardiovascular events in patients with type 2 diabetes and severe hypoglycemia. However, these trials also reported an increased hypoglycemia-associated mortality rate in patients allocated to standard treatment by a factor of 1.5-2 despite a significant 50 % to 70 % lower incidence of hypoglycemia compared to the intensive treatment group. Although the potential for a causal relationship has been demonstrated in mechanistic studies, the evidence from large prospective studies suggest that other pre-existing cardiovascular risk factors in addition to hypoglycemia may be the major link to the final cardiovascular event, and that a low blood glucose level can trigger these events in patients with a high cardiovascular risk.


Prognostic Factors for Cervical Spinal Cord Injury without Major Bone Injury in Elderly Patients.
In the current aging society, there has been a marked increase in the incidence of cervical spinal cord injury (CSCI) without major bone injury. This multi-center study aimed to identify predictors of neurological improvement in elderly patients with CSCI without major bone injury. The participants were 591 patients aged ≥65 years with CSCI without major bone injury and a minimum follow-up period of three months. Neurologic status was defined using the American Spinal Injury Association (ASIA) impairment scale (AIS). Univariate and multi-variate analyses were performed to identify prognostic factors for walking recovery in AIS A-C cases and full upper extremity motor recovery in AIS D cases. In AIS A-C cases, body mass index (odds ratio (OR): 1.112), magnetic resonance imaging signal change (OR: 0.240), AIS on admission (OR: 3.497), comorbidity of dementia/delirium (OR: 0.365), and post-injury pneumonia (OR: 0.194) were identified as independent prognostic factors for walking recovery. The prevalence of ossification of the posterior longitudinal ligament (OR: 0.494) was also found to be an independent prognostic factor in AIS B and C cases only. In AIS D cases, age (OR: 0.937), upper extremity ASIA motor score on admission (OR: 1.230 [per 5 scores]), and operation (OR: 0.519) were independent prognostic factors for full motor recovery. The severity of AIS at admission was the strongest predictor of functional outcomes. Promoting rehabilitation, however, through measures to reduce cognitive changes, post-injury pneumonia, and unhealthy body weight changes can contribute to greater neurological improvement in AIS A-C cases.


TRPM3 channel stimulated by pregnenolone sulphate in synovial fibroblasts and negatively coupled to hyaluronan.
Calcium-permeable channels are known to have roles in many mammalian cell types but the expression and contribution of such ion channels in synovial cells is mostly unknown. The objective of this study was to investigate the potential relevance of Transient Receptor Potential Melastatin 3 (TRPM3) channel to fibroblast-like synoviocytes (FLSs) of patients with rheumatoid arthritis. The study used RT-PCR and immunofluorescence to detect mRNA and protein. Intracellular calcium measurement detected channel activity in a FLS cell-line and primary cultures of FLSs from patients with rheumatoid arthritis. Enzyme-linked immunosorbent assays measured hyaluronan. Endogenous expression of TRPM3 was detected. Previously reported stimulators of TRPM3 sphingosine and pregnenolone sulphate evoked sustained elevation of intracellular calcium in FLSs. The FLS cell-line showed an initial transient response to sphingosine which may be explained by TRPV4 channels but was not observed in FLSs from patients. Blocking antibody targeted to TRPM3 inhibited sustained sphingosine and pregnenolone sulphate responses. Secretion of hyaluronan, which contributes adversely in rheumatoid arthritis, was suppressed by pregnenolone sulphate in FLSs from patients and the effect was blocked by anti-TRPM3 antibody. The data suggest that FLSs of patients with rheumatoid arthritis express TRPM3-containing ion channels that couple negatively to hyaluronan secretion and can be stimulated by pharmacological concentrations of pregnenolone sulphate.


Differential effects of natural and synthetic glucocorticoids on cytochrome 17alpha-hydroxylase (P-45017alpha) and cytochrome P-450 side-chain cleavage (P-450scc) messenger ribonucleic acid in the sheep placenta.
Our purpose was to determine differential effects of natural and synthetic glucocorticoids on cytochrome 17alpha-hydroxylase and cytochrome P-450 side-chain cleavage messenger ribonucleic acid in the sheep placenta and to determine whether feed-forward effects during labor are involved in further inducing placental cytochrome 17alpha-hydroxylase. Sheep underwent placement of myometrial electromyogram electrodes while they were under general anesthesia at 117 days' gestation. At 125 days' gestation either saline solution (early control animals not in labor, n = 5), 0.48 mg betamethasone during 48 hours (n = 7), 0.48 mg dexamethasone during 48 hours (n = 7), or 55 mg cortisol during a maximum of 96 hours (n = 4) was directly administered intravenously to the fetus. Necropsies were performed at 127 to 129 days' gestation. We also studied 6 ewes in spontaneous term labor at 143-147 days' gestation, 6 term control animals not in labor at 140 to 147 days' gestation, and 6 sheep in which myometrial activity was inhibited by intravenous infusion to the ewe of the selective cyclooxygenase 2 inhibitor nimesulide 9 hours after the onset of labor beginning at 147 to 148 days' gestation. Total fetal placental ribonucleic acid was analyzed by Northern blot with complementary deoxyribonucleic acid probes for cytochrome 17alpha-hydroxylase, cytochrome P-450 side-chain cleavage, and 18S ribosomal ribonucleic acid to correct for loading. Placental cytochrome 17alpha-hydroxylase messenger ribonucleic acid was detectable neither in term control animals not in labor nor in early control animals not in labor. Placental cytochrome 17alpha-hydroxylase messenger ribonucleic acid was induced in spontaneous term labor and all cortisol-infused sheep in labor with respect to term control animals not in labor and early control animals not in labor (P <.01). All betamethasone-infused sheep had myometrial contraction activity; however, only 4 of 7 had detectable placental cytochrome 17alpha-hydroxylase messenger ribonucleic acid. Placental cytochrome 17alpha-hydroxylase messenger ribonucleic acid was not detected in dexamethasone-infused sheep, even the 2 that had myometrial contractions. After reversal of the progression of spontaneous labor with nimesulide placental cytochrome 17alpha-hydroxylase messenger ribonucleic acid was significantly lower than the spontaneous term labor group (without nimesulide treatment). The placentas from all animals expressed cytochrome P-450 side-chain cleavage messenger ribonucleic acid, but no changes were associated with either gestational age studied (130 versus > 140 days' gestation) or glucocorticoid-induced premature labor and spontaneous term labor. (1) In sheep the expression of placental cytochrome 17alpha-hydroxylase is tightly associated with spontaneous term labor, and active synthesis of placental cytochrome 17alpha-hydroxylase is required during the progression of labor. (2) Cortisol is a more potent stimulator of placental cytochrome 17alpha-hydroxylase messenger ribonucleic acid in sheep than are synthetic glucocorticoids. (3) Betamethasone has a greater effect in inducing labor in sheep than does dexamethasone, possibly mediated through placental cytochrome 17alpha-hydroxylase.


Seasonal effects on testes size and sustained semen quality in captive golden-headed lion tamarins, Leontopithecus chrysomelas.
The golden-headed lion tamarin (Leontopithecus chrysomelas) is an endangered primate that, according to timing of births, there seems to have seasonal reproductive patterns in captive populations inhabiting the Southern Hemisphere. The extent to which male tamarins have circannual cyclic fluctuations in testicular functions, however, remains unknown. Changes in testis size and seminal variables, therefore, were evaluated during the rainy and dry seasons of the year in seven males. There was estimation of mating and birth seasons from the breeding colony using a 27 year database (229 birth records). Births were distributed throughout the year with peaks occurring in August-October and January-March (39.7 % and 30.5 % of all births, respectively). Semen collection using penile vibrostimulation was successfully induced in more than 96 % of the attempts regardless of the season (total of 75 ejaculates). Body mass did not vary significantly between seasons, but relative testes size was larger during the dry season. Values for none of the seminal variables (total sperm count, total and progressive motility, plasma membrane and acrosome integrity, and total sperm defects), however, were different during the rainy and dry seasons. These results indicate that testicular function in golden-headed lion tamarins may not be affected by daylength changes, and that seasonal patterns of female reproduction is perhaps more relevant for the reproductive timing of the species. Furthermore, the possibility of year-round production of ejaculates containing viable sperm broadens our perspective of preserving genetic diversity within the species because there is a greater opportunity for semen collection and freezing.


Capability for daily activities in old people with rheumatoid arthritis: a population based study.
To describe the functional capacity for daily activities in old people with clinical rheumatoid arthritis (including juvenile rheumatoid arthritis (JRA)) in a population based cohort. A cohort of 700 people was randomly collected from the population older than 75 years in a Finnish town. Altogether 601 persons (86%) participated. Data were collected from clinical records and by interview, clinical examination, and questionnaire. Ability to carry out activities of daily living (ADL) was assessed by the Barthel index, and the IADL (instrumental activities of daily living) by the Lawton and Brody questionnaire. 16 people had clinical rheumatoid arthritis (one with JRA). The prevalence was 16/601 (2.7% (95% confidence interval, 1.7% to 4.5%)). Eight patients with rheumatoid arthritis (50%) obtained the best possible ADL figures, while three (19%) had very poor results. Seven (44%) could not dress themselves without help. Three (19%) were unable to walk, and five (31%) could not climb stairs. Sex and age adjusted results showed no statistical difference (ADL and IADL) between patients with clinical rheumatoid arthritis and rest of the cohort. Four patients (25%) had dementia, which was associated with the poor functional capacity. The prevalence of the disease was unexceptional. The ability of old people with rheumatoid arthritis to carry out activities of daily living did not differ from the general population, but the disease may lead to severe disability on an individual level, especially when associated with dementia. It therefore remains a considerable challenge to the health care and social systems.


MIMOSA2: a metabolic network-based tool for inferring mechanism-supported relationships in microbiome-metabolome data.
Recent technological developments have facilitated an expansion of microbiome-metabolome studies, in which samples are assayed using both genomic and metabolomic technologies to characterize the abundances of microbial taxa and metabolites. A common goal of these studies is to identify microbial species or genes that contribute to differences in metabolite levels across samples. Previous work indicated that integrating these datasets with reference knowledge on microbial metabolic capacities may enable more precise and confident inference of microbe-metabolite links. We present MIMOSA2, an R package and web application for model-based integrative analysis of microbiome-metabolome datasets. MIMOSA2 uses genomic and metabolic reference databases to construct a community metabolic model based on microbiome data and uses this model to predict differences in metabolite levels across samples. These predictions are compared with metabolomics data to identify putative microbiome-governed metabolites and taxonomic contributors to metabolite variation. MIMOSA2 supports various input data types and customization with user-defined metabolic pathways. We establish MIMOSA2's ability to identify ground truth microbial mechanisms in simulation datasets, compare its results with experimentally inferred mechanisms in honeybee microbiota, and demonstrate its application in two human studies of inflammatory bowel disease. Overall, MIMOSA2 combines reference databases, a validated statistical framework, and a user-friendly interface to facilitate modeling and evaluating relationships between members of the microbiota and their metabolic products. MIMOSA2 is implemented in R under the GNU General Public License v3.0 and is freely available as a web server at http://elbo-spice.cs.tau.ac.il/shiny/MIMOSA2shiny/ and as an R package from http://www.borensteinlab.com/software_MIMOSA2.html. Supplementary data are available at Bioinformatics online.


Immature human cord blood progenitors engraft and proliferate to high levels in severe combined immunodeficient mice.
Unseparated or Ficoll-Hypaque (Pharmacia, Piscataway, NJ)--fractionated human cord blood cells were transplanted into sublethally irradiated severe combined immunodeficient (SCID) mice. High levels of multilineage engraftment, including myeloid and lymphoid lineages, were obtained with 80% of the donor samples as assessed by DNA analysis, fluorescence-activated cell sorting (FACS), and morphology. In contrast to previous and concurrent studies with adult human bone marrow (BM), treatment with human cytokines was not required to establish high-level human cell engraftment, suggesting that neonatal cells either respond differently to the murine microenvironment or they provide their own cytokines in a paracrine fashion. Committed and multipotential myelo-erythroid progenitors were detected using in vitro colony assays and FACS analysis of the murine BM showed the presence of immature CD34+ cells. In addition, human hematopoiesis was maintained for at least 14 weeks providing further evidence that immature hematopoietic precursors had engrafted the murine BM. This in vivo model for human cord blood-derived hematopoiesis will be useful to gain new insights into the biology of neonatal hematopoietic cells and to evaluate their role in gene therapy. There is growing evidence that there are ontogeny-related changes in immature human hematopoietic cells, and therefore, the animal models we have developed for adult and neonatal human hematopoiesis provide useful tools to evaluate these changes in vivo.


The Clinical Implication of Incidental Prostatic Amyloidosis.
To describe the clinicopathologic features of patients with incidental prostatic amyloidosis. We queried the genitourinary pathology database at Mayo Clinic Arizona for prostate specimens which showed amyloid deposits. Congo red stain was used for the diagnosis of amyloidosis and amyloid subtype was performed analysis using Liquid chromatography tandem mass spectrometry. We reviewed the patient's medical charts for past or subsequent diagnosis of systemic amyloidosis and clinical course. Prostatic amyloidosis was identified in 7 patients between 2008-2018. Median age was 79 years (range 69-84) and median follow-up was 5 years (range 0-11). Benign prostate tissue was found in 4 patients, and prostate cancer was diagnosed in 3 patients. Amyloid subtyping was available in 6 patients and was consistent with Amyloid transthyretin Amyloidosis. Liquid chromatography tandem mass spectrometry did not detect an amino acid sequence abnormality in the transthyretin protein in any of the patients. Five of 6 patients were diagnosed with cardiac amyloidosis, which preceded and followed the diagnosis of prostatic amyloidosis in 1 and 4 patients, respectively. Of these 4 patients, 2 were diagnosed immediately and as a consequence of the diagnosis of prostatic amyloidosis, and the remaining 2 3 and 4 years later. Incidental prostatic amyloidosis should prompt systemic and cardiac evaluation for amyloidosis. In patients with suspected cardiac amyloidosis, prior prostate specimens should be reviewed for the presence of amyloidosis.