Investigations of leukocyte and inflammatory markers in pregnancies complicated by preeclampsia.
Preeclampsia is a frequent and potentially fatal pregnancy complication. It can be challenging to make a timely diagnosis. Identifying clinically useful biochemical markers would be a remedying tool to support the diagnosis of preeclampsia. The aim was to investigate differential cell counts and acute phase reactants as diagnostic markers of preeclamptic third-trimester pregnancies and in relation to pregnancy term, gravidity and the severity of hypertension. Based on a cohort of 421 pregnant women, we included 174 participants (case n = 84, control n = 90) during the third trimester. Peripheral blood was sampled to measure differential white blood cell counts and acute phase reactants on the day of inclusion. The neutrophil-to-lymphocyte ratio and plasma haptoglobin levels were significantly increased in healthy pregnancies compared with preeclamptic pregnancies. Plasma ferritin levels and albumin levels were respectively increased and decreased in cases of preeclampsia compared with controls. Albumin was specific among multigravida. Plasma transferrin and high-sensitivity C-reactive protein (hs-CRP) levels were significantly decreased and increased, respectively, in cases with preterm preeclampsia compared with term preeclampsia. Plasma ferritin and albumin levels reflected higher inflammation in cases with preeclampsia compared with healthy pregnancies; the same did plasma transferrin and hs-CRP levels in preterm versus term preeclampsia. When considering the normal ranges plasma albumin and hs-CRP levels identified preeclamptic from healthy third-trimester pregnancies and preterm from term preeclampsia cases, respectively, with near-acceptable diagnostic performances. Further validation of the diagnostic value will require larger sample-sized studies with paired plasma and serum samples.


Modeling the cost-effectiveness of insect rearing on artificial diets: A test with a tephritid fly used in the sterile insect technique.
We modeled the cost-effectiveness of rearing Anastrepha ludens, a major fruit fly pest currently mass reared for sterilization and release in pest control programs implementing the sterile insect technique (SIT). An optimization model was generated by combining response surface models of artificial diet cost savings with models of A. ludens pupation, pupal weight, larval development time and adult emergence as a function of mixtures of yeast, a costly ingredient, with corn flour and corncob fractions in the diet. Our model revealed several yeast-reduced mixtures that could be used to prepare diets that were considerably cheaper than a standard diet used for mass rearing. Models predicted a similar production of insects (pupation and adult emergence), with statistically similar pupal weights and larval development times between yeast-reduced diets and the standard mass rearing diet formulation. Annual savings from using the modified diets could be up to 5.9% of the annual cost of yeast, corn flour and corncob fractions used in the standard diet, representing a potential saving of US $27.45 per ton of diet (US $47,496 in the case of the mean annual production of 1,730.29 tons of artificial diet in the Moscafrut mass rearing facility at Metapa, Chiapas, Mexico). Implementation of the yeast-reduced diet on an experimental scale at mass rearing facilities is still required to confirm the suitability of new mixtures of artificial diet for rearing A. ludens for use in SIT. This should include the examination of critical quality control parameters of flies such as adult flight ability, starvation resistance and male sexual competitiveness across various generations. The method used here could be useful for improving the cost-effectiveness of invertebrate or vertebrate mass rearing diets worldwide.


Capillary electrokinetic chromatography of insulin and related synthetic analogues.
With the implementation of recombinant DNA technology in the pharmaceutical industry, some synthetic insulins have been developed in order to improve the therapy of diabetes. These analogues differ only slightly in the amino acid sequence, therefore displaying a great challenge for analytical chemistry. Within the work presented in this paper, capillary zone electrophoresis (CZE), micellar electrokinetic chromatography (MEKC) with sodium dodecylsulphate (SDS) as micelle-forming agent, and microemulsion electrokinetic chromatography (MEEKC) with microemulsions consisting of SDS, n-octane and 1-butanol were investigated for the separation of human insulin and five synthetic analogues. Best results were achieved with a solvent-modified MEKC system consisting of 100mM sodium dodecyl sulphate and 15% acetonitrile in 10mM borate buffer (pH 9.2). A similar system based on perfluorooctanoic acid as micelle-forming agent in ammonium acetate (pH 9.2) was successfully employed for the hyphenation with a quadrupole/time-of-flight mass spectrometer via a sheath-flow interface. In this case, detection limits at 10mg/L could be achieved.


Concordance of physical activity trajectories among middle-aged and older married couples: impact of diseases and functional difficulties.
This study examined spousal concordance of physical activity trajectories among middle-aged and older married couples and the influences of recent diseases and functional difficulties on individuals' trajectories and those of their spouses'. Participants included 5,074 married couples aged 50 or older in the Health and Retirement Study in 2004-2010. Participants were categorized into 4 physical activity trajectories (i.e., stable active, adopters, relapsers, and stable sedentary) using confirmatory latent class growth analysis. Individuals' trajectory memberships were predicted by their spouses' memberships, together with recent diseases and functional difficulties of both couple members. In the main, corresponding husbands' trajectories predicted wives' trajectories and vice versa. More functional difficulties predicted higher likelihoods of unfavorable trajectories among individuals but not of their spouses'. Among wives, more recent diseases predicted slightly more physical activity in subsequent data waves but not trajectory memberships. Results supported spousal concordance in physical activity trajectories. The negative impact of functional difficulties was considerably contained within individuals. Increases in physical activity after acquiring diseases among wives were small and short lived. More research is needed to understand the underlying processes, which can be used to improve the design of future physical activity interventions directed toward women, men, and couples.


Immotile-cilia syndrome with azoospermia: a case report and review of the literature.
A case of immotile-cilia syndrome associated with azoospermia is presented. This diagnosis is based on a typical history of bronchitis, sinusitis, situs inversus, impaired nasal mucociliary clearance and characteristic ultrastructural defect in the respiratory tract cilia and in the sperm tail. Semen analysis showed azoospermia with no evidence of obstruction in the epididymis or vas deferens; there was normal spermatogenesis.


Spanish-English Bilingual Children with Psychopathology: Language Deficits and Academic Language Proficiency.
BACKGROUND: The aim was to study the language profiles of a well-characterised sample (n = 50) of Spanish-English bilingual children consecutively referred to psychiatric services. METHODS: Spanish and English language profiles were assessed with the Woodcock Language Proficiency Battery-Revised (WLPB). Profiles included language ability levels, deficits and dominance in five expressive and receptive/expressive domains, and academic (school-related) language proficiency levels. RESULTS: General language ability was low for 69% in either language and for 51% in both. Language dominance data suggested that expressive skills were dominant in English. In 73% of the children, ability to function at school in the strongest language is 'limited', defined by the WLPB as incorrect responses to 50% of the items typically answered correctly by children of the same age. Classroom language demands, also according to the WLPB, would be 'extremely difficult' to 'impossible' for 40% of the children in at least one language, and for 19% in either language. CONCLUSIONS: Language deficits, present in many psychiatrically-referred bilingual children, ought to be suspected by the clinician. The typical language demands of schooling appear to be overwhelming for many of these children, with ensuing implications for psychosocial adaptation and educational attainment. Thorough language ability assessments of both languages are often necessary for the early detection of language deficits and for understanding how dual language abilities relate to psychiatric symptoms. Therefore, language assessment services need to be closely linked to programs serving psychiatrically-referred bilingual children. Other implications of this research for clinical practice are discussed.


Euthanasia in Colombia: Experience in a palliative care program and bioethical reflections.
The increased prevalence of advanced-stage chronic diseases has augmented the need for palliative care teams. In Colombia, although the legislation promotes palliative care development, people still die without receiving management from a palliative care team. In addition, judiciary regulations regarding euthanasia have generated public confusion and ethical conflicts among members of the palliative care teams. Therefore, this study aimed to perform a bioethical reflection on the relationship between palliative care and euthanasia supported by data on euthanasia requests in a palliative care program. This reflection is based on retrospective and descriptive observational data, collected in two highly complex hospitals in Bogotá, Colombia. A total of 50 euthanasia requests were identified, of which 62% met the defined criteria, 16% did not, and 22% were not considered by the interdisciplinary committee for the right to die with dignity due to early death. All patients were treated and followed up by a palliative care team until their death. This study considered that palliative care could be a complement management for patients requesting euthanasia based on their experience by supporting the decision-making, alleviating suffering, and providing emotional support in the last days of life.


Amperometric glucose biosensor based on adsorption of glucose oxidase at platinum nanoparticle-modified carbon nanotube electrode.
A new amperometric biosensor, based on adsorption of glucose oxidase (GOD) at the platinum nanoparticle-modified carbon nanotube (CNT) electrode, is presented in this article. CNTs were grown directly on the graphite substrate. The resulting GOD/Pt/CNT electrode was covered by a thin layer of Nafion to avoid the loss of GOD in determination and to improve the anti-interferent ability. The morphologies and electrochemical performance of the CNT, Pt/CNT, and Nafion/GOD/Pt/CNT electrodes have been investigated by scanning electron microscopy, cyclic voltammetry, and amperometric methods. The excellent electrocatalytic activity and special three-dimensional structure of the enzyme electrode result in good characteristics such as a large determination range (0.1-13.5mM), a short response time (within 5s), a large current density (1.176 mA cm(-2)), and high sensitivity (91mA M(-1)cm(-2)) and stability (73.5% remains after 22 days). In addition, effects of pH value, applied potential, electrode construction, and electroactive interferents on the amperometric response of the sensor were investigated and discussed. The reproducibility and applicability to whole blood analysis of the enzyme electrode were also evaluated.


Dutasteride: a review of current data on a novel dual inhibitor of 5alpha reductase.
Dutasteride is used in the treatment of benign prostatic hyperplasia. Like finasteride, it reduces serum prostate-specific antigen levels by approximately 50% at 6 months and total prostate volume by 25% in 2 years. It differs from finasteride in that it inhibits both isoenzymes of 5alpha reductase and results in near-complete suppression of serum dihydrotestosterone. Randomized placebo-controlled trials over 2 years have shown the efficacy of dutasteride in symptomatic relief, improvements in quality of life and peak urinary flow rate, and reduction of acute urinary retention events and need for surgery. Side effects occurring in therapy with dutasteride are decreased libido, erectile dysfunction, ejaculation disorders, and gynecomastia. However, when dutasteride treatment is compared with placebo, these sexual adverse events are only modestly elevated. Long-term use over 4 years did not increase side effects. An efficient treatment of side effects is the combination of dutasteride and tamsulosin, especially for patients with large prostate volumes. Finally, the anticancer properties of dutasteride have been shown in placebo-controlled trials and are being investigated in the ongoing Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial.


The Needle and the Damage Done: Framing the Heroin Epidemic in the Cincinnati Enquirer.
This case study focuses on the Cincinnati Enquirer's coverage of the heroin epidemic. The Enquirer started the first heroin beat in January 2016, and it could serve as a model for other news organizations. Reporters used combinations of episodic, thematic, public health, and crime and law enforcement frames in their coverage. These news frames are discussed in terms of how individualism-collectivism, geographic location, available resources, and social determinants inform journalistic and societal discussions of the heroin epidemic in terms of solutions instead of responsibility or blame.


svapls: an R package to correct for hidden factors of variability in gene expression studies.
Hidden variability is a fundamentally important issue in the context of gene expression studies. Collected tissue samples may have a wide variety of hidden effects that may alter their transcriptional landscape significantly. As a result their actual differential expression pattern can be potentially distorted, leading to inaccurate results from a genome-wide testing for the important transcripts. We present an R package svapls that can be used to identify several types of unknown sample-specific sources of heterogeneity in a gene expression study and adjust for them in order to provide a more accurate inference on the original expression pattern of the genes over different varieties of samples. The proposed method implements Partial Least Squares regression to extract the hidden signals of sample-specific heterogeneity in the data and uses them to find the genes that are actually correlated with the phenotype of interest. We also compare our package with three other popular softwares for testing differential gene expression along with a detailed illustration on the widely popular Golub dataset. Results from the sensitivity analyes on simulated data with widely different hidden variation patterns reveal the improved detection power of our R package compared to the other softwares along with reasonably smaller error rates. Application on the real-life dataset exhibits the efficacy of the R package in detecting potential batch effects from the dataset. Overall, Our R package provides the user with a simplified framework for analyzing gene expression data with a wide range of hidden variation patterns and delivering a differential gene expression analysis with substantially improved power and accuracy.The R package svapls is freely available at http://cran.r-project.org/web/packages/svapls/index.html.


Chinese dyslexics show neural differences in morphological processing.
Previous behavioral studies have suggested that morphological awareness is impaired in Chinese children with reading disability (RD), but how this is reflected in brain alterations is not known. Using functional magnetic resonance imaging (fMRI), the current study compared morphological processing in a RD group (11-13 years old) to an age-matched typically developing (TD) group. Participants made semantic relatedness judgments to incongruent word pairs that were either semantically related but did not share a morpheme or semantically unrelated but did share a morpheme. This was compared to conditions where semantic relatedness and morphemic information was congruent. A smaller incongruency effect was found in left dorsal posterior (BA9) and ventral anterior (BA47) inferior frontal gyrus (IFG) in the RD compared to the TD, suggesting that the RD is less sensitive to morphological information. This was a specific deficit as a phonological control task that manipulated congruency between orthography and phonology did not show group differences in the IFG. Moreover, brain activation in the IFG for the incongruency effect in the semantic task was negatively correlated with reading skill for the RD group only, suggesting that higher skill children with RD may rely on a compensatory whole-word strategy by ignoring the morphemic information.


Spontaneous intramural oesophageal haematoma: an unusual cause of chest pain.
The following case describes a 29-year-old previously well gentleman who presented with an acute onset of chest pain, dysphagia, odynophagia and vomiting without haematemesis. An oesophageal lesion was visualised on CT angiography and further investigation via oesophogastroduodenoscopy (OGD) diagnosed a spontaneous intramural oesophageal haematoma as the cause of his symptomatology. Conservative medical management in the form of triple therapy and softened diet was well tolerated and a follow-up OGD at 6 weeks after discharge from hospital showed spontaneous resolution of the haematoma.


Isoform function prediction based on bi-random walks on a heterogeneous network.
Alternative splicing contributes to the functional diversity of protein species and the proteoforms translated from alternatively spliced isoforms of a gene actually execute the biological functions. Computationally predicting the functions of genes has been studied for decades. However, how to distinguish the functional annotations of isoforms, whose annotations are essential for understanding developmental abnormalities and cancers, is rarely explored. The main bottleneck is that functional annotations of isoforms are generally unavailable and functional genomic databases universally store the functional annotations at the gene level. We propose IsoFun to accomplish Isoform Function prediction based on bi-random walks on a heterogeneous network. IsoFun firstly constructs an isoform functional association network based on the expression profiles of isoforms derived from multiple RNA-seq datasets. Next, IsoFun uses the available Gene Ontology annotations of genes, gene-gene interactions and the relations between genes and isoforms to construct a heterogeneous network. After this, IsoFun performs a tailored bi-random walk on the heterogeneous network to predict the association between GO terms and isoforms, thus accomplishing the prediction of GO annotations of isoforms. Experimental results show that IsoFun significantly outperforms the state-of-the-art algorithms and improves the area under the receiver-operating curve (AUROC) and the area under the precision-recall curve (AUPRC) by 17% and 44% at the gene-level, respectively. We further validated the performance of IsoFun on the genes ADAM15 and BCL2L1. IsoFun accurately differentiates the functions of respective isoforms of these two genes. The code of IsoFun is available at http://mlda.swu.edu.cn/codes.php? name=IsoFun. Supplementary data are available at Bioinformatics online.


Enhancement by reproterol of the ability of disodium cromoglycate to stabilize rat mastocytes.
The beta2-adrenoceptor agonist reproterol and disodium cromoglycate (DSCG) are used in fixed combination for the treatment of asthma, because they act on bronchial smooth muscle and inflammatory cells, respectively. Here, we investigated if reproterol can also act in rat mast cells in vitro to facilitate the inhibitory action of disodium cromoglycate (DSCG) on histamine secretion induced by compound 48/80. Reproterol was as potent as DSCG to inhibit histamine release in rat mast cells (32.8+/-6.0 vs. 36.7+/-6.2% at 1 microM of each compound, n=10 and n=8 respectively). Mast cell stabilization by DSCG (1-100 microM) was strongly and significantly enhanced in the presence of a fixed saturating concentration of reproterol (100 microM). Conversely, the combination of DSCG (1-100 microM) with the beta2-agonist used as reference compound, salbutamol (100 microM) did not inhibit histamine release more than DSCG alone. In combination with a saturating concentration of DSCG (100 microM), reproterol inhibited histamine release more than reproterol alone. The potent adenylate cyclase stimulator forskolin (50 microM) was able to inhibit histamine release to a similar extent as DSCG and significantly (P<0.05) enhanced the inhibition of histamine release by DSCG. Finally, the phosphodiesterase inhibitor theophylline (100 microM) was equipotent to reproterol and DSCG in stabilizing rat mast cells. In conclusion, reproterol enhances the ability of disodium cromoglycate to stabilize rat mast cells. This effect is not shared by salbutamol and can be, at least in part, independent of beta2-adrenoceptor stimulation.


Interferon alfa-2b three times daily and thalidomide in the treatment of metastatic renal cell carcinoma.
The antiangiogenic effect of interferon (IFN) may improve with frequent dosing and by combination with other agents with antiangiogenic activity. To evaluate this potential, we treated patients with metastatic renal cell carcinoma (RCC) with frequently dosed IFN and thalidomide. Thirty patients were given IFN-alpha-2b 0.9 MU subcutaneously three times daily for 1 month and subsequently 1.2 MU tid unless serious toxicity was encountered. Thalidomide was first given 100 mg/d for 1 week and 300 mg/d thereafter. Sera were collected before and during treatment for serum vascular endothelial growth factor (S-VEGF) analyses performed using enzyme-linked immunosorbent assay. The intention-to-treat response rate was 20% (95% CI, 6% to 34%) and response rate for assessable patients (n = 27) was 22% (95% CI, 6% to 38%). All responses were partial. In addition, 17 patients (63%; 95% CI, 45% to 81%) had stable disease for 3 months or longer. The median time to treatment failure was 7.7 months, and median survival time was 14.9 months. The most common cause of thalidomide discontinuation was neuropathy. S-VEGF levels decreased more in patients who responded to therapy compared with those in patients whose condition had stabilized or who had progressive disease (P =.036). The combination of frequently dosed IFN-alpha-2b and low-dose thalidomide is feasible and active in advanced RCC, but the clinical benefit may remain small compared with that of IFN alone. Results from an ongoing phase III trial comparing IFN-alpha with or without thalidomide need to be analyzed before this combination can be recommended for use outside clinical studies.


One-dose vaccination associated with attenuated disease severity of adolescent and adult varicella cases in Beijing's Fengtai District.
In recent years, the number of varicella cases in adults has significantly increased in Beijing. However, the effect of the vaccination on varicella-related characteristics among adults has not been studied. Using data from the Infectious Disease Reporting System and the Immunization Information System, we compared the epidemiology and disease severity in breakthrough and unvaccinated varicella cases in adolescents and adults (≥ 15 year-old) from 2008 to 2011 in Beijing's Fengtai district, China. The results showed that the age (P = 0.003),contact history (90% vs. 73%, P = 0.019) and outbreak cases (10% vs. 1%, P < 0.0001) were significantly differently distributed between the two groups and that both the incidence of moderate-to-severe cases (26% vs. 45%, P = 0.035, OR = 0.446) and varicella-associated fever (49% vs. 66%, P = 0.068, OR = 0.534) were either significantly lower or trended to be lower in the breakthrough group than in the unvaccinated group. Additionally,vaccine effectiveness against moderate-to-severe cases of varicella was 55.4%. Altogether, these results indicate that vaccination against varicella among adolescents and adults affected the epidemiology and attenuated the disease severity of the cases. The Results from this study will provide useful information for the prevention of varicella in adolescents and adults.


Modulation by protein kinase C of arachidonic acid release from permeabilised myometrial cells of guinea pig uterus.
The effects of protein kinase C activation on phospholipase A2 and phospholipase C activity in permeabilised cultured myometrial cells from guinea pig uterus have been studied. Phospholipase A2 activity was followed by measurement of [3H]arachidonic acid release from [3H]arachidonic acid-prelabelled membrane lipids. [3H]Arachidonic acid release was stimulated by Ca2+ at 1-10 microM and by GTP gamma S at 1 microM to 1 mM in the presence of 10 microM Ca2+. The activation by calcium was enhanced 89.5 +/- 12.7% (P < 0.01) in the presence of 1 microM phorbol 12-myristate 13-acetate (PMA) and that by 1 microM GTP gamma S by 65.4 +/- 4.4% (P < 0.001). The PMA enhancement of arachidonic acid release was completely blocked by 3 microM staurosporine. Phospholipase C activation was followed by measurement of [3H]inositol polyphosphate production from [3H]inositol-prelabelled membrane lipids. This was stimulated by Ca2+ at 0.1 and 10 microM and by 1 and 50 microM GTP gamma S. PMA at 1 microM caused a consistent reduction in the extent of Ca2+ and GTP gamma S-stimulated inositol polyphosphate production and 3 microM reversed the inhibitory action of PMA. The data are consistent with arachidonic acid release in permeabilised myometrial cells from guinea pigs reflecting in large part phospholipase A2 activation and with that pathway being stimulated by protein kinase C activation. They are also consistent with protein kinase C activation causing reduction in phospholipase C pathways in uterine myocytes, at least as measured by inositol polyphosphate release.


MicroRNAs, wild-type and mutant p53: more questions than answers.
The tumor suppressor p53 is a sequence-specific transcription factor that activates the expression of genes involved in apoptosis, cell cycle arrest and senescence. p53 can also inhibit gene expression and this effect is partly mediated by inducing several microRNAs (miRNAs). MiRNAs have emerged as a new class of regulators of the expression and function of eukaryotic genomes. Tumor suppressive or oncogenic functions have been attributed to some miRNAs. Recent studies have shown that p53 can alter the transcription of several miRNAs, and in some cases, it can also influence miRNA maturation. Conversely, miRNAs can also modulate the abundance and activity of p53 by direct or indirect mechanisms. Moreover, mutant p53 can actively repress the expression of some miRNAs that are activated by wild-type p53. In this review, we discuss recent evidences of this crosstalk between miRNAs and the p53 network and also highlight its implications in cancer.


Somatic stem cells in the human endometrium.
The existence of human endometrial somatic stem cells was proposed in the mid-20th century for the first time. This hypothesis became stronger and was revised by two authors between 1978 and 1989. Nevertheless, it was not until 2004 that scientific evidence was first published. As we describe here, the great regenerative capability of the human endometrium has been finally questioned in the last 8 years, and this period can be considered the most productive in endometrial stem cell biology given the new scientific information recapitulated to date. We provide a detailed summary based on the actual scientific knowledge obtained about (1) the existence of somatic stem cells in murine (detected with label-retaining cell methods) and human (cells isolated by different methods) endometria, (2) the involvement of bone marrow as a putative extrauterine source of endometrial somatic stem cells, (3) the implication and biological pathways of these cells in several pathologies like endometriosis and endometrial cancer, and (4) the future of endometrial somatic stem cells in regenerative medicine to provide new strategies in autologous transplant and bioengineering.


Malaria--Great Exuma, Bahamas, May-June 2006.
Malaria in humans is caused by four distinct protozoan species of the genus Plasmodium (P. falciparum, P. vivax, P. ovale, and P. malariae). These parasites are transmitted by the bite of an infective female Anopheles mosquito. In the Caribbean region, malaria has been eliminated from all islands except Hispaniola, the island consisting of Haiti and the Dominican Republic. Elimination of malaria elsewhere resulted from a combination of integrated control measures, socioeconomic development, and close public health surveillance. However, even Caribbean islands where malaria is no longer endemic remain at constant risk for reintroduction of the disease because of their tropical climate, presence of competent malaria vectors, and proximity to other countries where malaria is endemic. This susceptibility was underscored by the recent outbreak of malaria on the island of Great Exuma in the Bahamas; during May-June 2006, a total of 19 malaria cases were identified. Four of the cases, in travelers from North America and Europe, are described in this report; such cases of imported malaria can signal the presence of a malaria problem in the country visited and thus assist local health authorities in their investigations. On September 19, after 3 months with no report of new cases, CDC rescinded its previous recommendation that U.S.-based travelers take preventive doses of the antimalarial drug chloroquine before, during, and after travel to Great Exuma.


Phylogenetic relationships among monogenean gill parasites (Dactylogyridea, Ancyrocephalidae) infesting tilapiine hosts (Cichlidae): systematic and evolutionary implications.
We studied the systematics of 14 species of monogenean (Ancyrocephalidae) gill parasites from West African tilapiine hosts (Cichlidae) using both morphological and genetic data. With these tools, we were able to: (i) confirm the validity of the previously described morphological parasite species and of the genus Scutogyrus; (ii) propose that some stenoxenous species (i.e., parasite species with more than one host) may be composed of sister species (e.g., Cichlidogyrus tilapiae); (iii) state that the use of the morphology of the haptoral sclerites is more suitable to infer phylogenetic relationships than the morphology of the genitalia (which seems to be more useful to resolve species-level identifications, presumably because of its faster rate of change). These results imply that: (i) the specificity of these monogenean parasites is greater than initially supposed (what were thought to be stenoxenous species may be assemblages of oïoxenous sister species); (ii) related species groups (i.e., "tilapiae," "halli," and "tiberianus") have to be, as genus Scutogyrus, validated within the 54 ancyrocephalid species described from 18 species of tilapiine hosts in West Africa, (iii) the group "tilapiae," due to its morphology and host range, have to be considered as being the most primitive; (iv) the occurrence of lateral transfers and parallel speciation processes are necessary to describe the repartition of the newly described parasite groups on the three host genera studied (Tilapia, Oreochromis, and Sarotherodon).


Effect of a training programme on knowledge of nurses from a missionary hospital in India regarding breast cancer and its screening.
A cross-sectional study was conducted among nursing staff of a missionary hospital of Delhi in June 2009. All the nurses were invited to participate in the training programme on breast cancer and techniques of breast self examination (BSE). A questionnaire was administered to all 259 participants seeking information on their level of awareness regarding breast cancer and relevant screening guidelines. With the help of 5 training workshops all the nurses were imparted training regarding the most appropriate technique of doing breast self exams. The mean age of the participants was 35.8 years. Out of a total of 259 nursing staff members 77.2% correctly answered all the 10 questions regarding high risk factors for breast cancer and after the training programme this increased to 100% (p<0.05). Only 65.2% of the participants gave correct responses to all the 8 questions regarding correct technique of performing a BSE, which after the training programme increased to 99.3% (p<0.05). At the baseline only 56.8% knew all the three screening methods correctly and after the intervention 98.7% could correctly mark the responses regarding screening (p<0.05). The actual practice of following the screening guidelines amongst the nursing staff was poor. Only 26 (10.03%) had ever done a BSE, none performed it monthly, 58 (22.4%) had ever gone themselves for a CBE and 18 (6. 94%) had ever undergone mammography.


Antidiarrheal Effect of Zornia brasiliensis Vogel (Leguminosae) on Mice Involves Adrenergic Pathway Activation.
Several secondary metabolites have been isolated from Zornia brasiliensis (Leguminosae), mainly flavonoids. These compounds are known for many pharmacological actions, such as antispasmodic and antidiarrheal. Therefore, we evaluated the antidiarrheal effect of the ethanolic extract obtained from Zornia brasiliensis aerial parts (ZB-EtOHAP), as well as its underlying mechanisms. Castor-oil-induced diarrhea, fluid accumulation, and intestinal transit (normal and castor oil induced) were performed to assess the antidiarrheal, antisecretory, and antipropulsive activities of the extract. The involvement of opioid and adrenergic pathways was also investigated. ZB-EtOHAP inhibited, in a dose-dependent manner, both total defecation frequency and the number of watery stools. The extract showed no effect on fluid accumulation or normal intestinal transit. On the other hand, when the animals were pretreated with castor oil, the extract decreased the distance traveled by the marker in the small intestine. Investigation of the involvement of opioid and adrenergic systems showed that the pharmacological potency of the extract did not change in the presence of naloxone, but it was reduced in the presence of yohimbine. The data indicate that Zornia brasiliensis has an antidiarrheal effect due to inhibition of the intestinal motility through adrenergic pathway activation.


Pil1 controls eisosome biogenesis.
The molecular composition of plasma membranes is constantly remodeled by endocytosis and exocytosis. Eisosomes are large cytoplasmic protein assemblies that localize to specialized domains on the yeast plasma membrane. They are of uniform size and immobile, and their disruption leads to large aberrant plasma membrane invaginations and endocytic defects. It is unknown how eisosomes are formed or inherited and what governs their size, distribution, and location. Here we show that eisosomes are formed de novo in the bud of dividing cells. They colonize newly formed membrane at a fixed density in a polarized wave proceeding from the bud neck to the bud tip and become anchored at the site of their formation. Pil1, one of the two main eisosome subunits, emerges as the central regulator of eisosome biogenesis that determines both size and location of eisosomes. Lowering Pil1 expression leads to normal-sized eisosomes at a reduced density, suggesting that eisosomes must be of a minimal size. Conversely, raising Pil1 expression leads to larger eisosomes at a fixed density, suggesting that under these conditions eisosome nucleation sites are limiting. Pil1 expression is regulated by the cell cycle, which synchronizes eisosome formation with plasma membrane growth. Our results establish a first framework of the molecular principles that define eisosome assembly and distribution.


IoT-IIRS: Internet of Things based intelligent-irrigation recommendation system using machine learning approach for efficient water usage.
In the traditional irrigation process, a huge amount of water consumption is required which leads to water wastage. To reduce the wasting of water for this tedious task, an intelligent irrigation system is urgently needed. The era of machine learning (ML) and the Internet of Things (IoT) brings it is a great advantage of building an intelligent system that performs this task automatically with minimal human effort. In this study, an IoT enabled ML-trained recommendation system is proposed for efficient water usage with the nominal intervention of farmers. IoT devices are deployed in the crop field to precisely collect the ground and environmental details. The gathered data are forwarded and stored in a cloud-based server, which applies ML approaches to analyze data and suggest irrigation to the farmer. To make the system robust and adaptive, an inbuilt feedback mechanism is added to this recommendation system. The experimentation, reveals that the proposed system performs quite well on our own collected dataset and National Institute of Technology (NIT) Raipur crop dataset.


Peroneus Quartus Muscle AutograftA Novel Approach to the Repair of a Split Peroneus Brevis Tendon Tear.
This case report highlights a novel approach to strengthening the repair of a split peroneus brevis tendon tear with a peroneus quartus muscle autograft. We describe a 51-year-old woman with a longitudinal split tear of the peroneus brevis tendon confirmed by magnetic resonance imaging. Intraoperatively, a peroneus quartus muscle was appreciated, resected, and used as an autograft in the repair of the peroneus brevis tendon. Use of a peroneus quartus muscle as an autograft in peroneal tendon repair has not been documented in the literature, to our knowledge.


The Effects of Primary Brain Tumors on Vision and Quality of Life in Pediatric Patients.
Brain tumors are the leading cause of death from childhood cancer. Overall survival has improved due to earlier detection, better therapies, and improved posttreatment surveillance. Permanent sequelae of the tumor and its treatment may cause severe impairment and decreased quality of life (QoL). Pediatric primary brain tumor patients' vision can be severely affected, even when the tumor location does not primarily involve the visual pathway. Visual dysfunction and impaired vision-related QoL may not be detected or screened for in children with primary brain tumors for many reasons, including examination difficulty and lack of awareness. The authors review the ophthalmic presenting symptoms, effects on vision, and quality of life in pediatric patients with primary brain tumors. They also describe and emphasize the importance of systematic neuro-ophthalmologic examinations in this population, which may improve long-term visual and QoL outcomes through earlier interventions.


Test-retest reliability of the novel 5-HT1B receptor PET radioligand [11C]P943.
[(11)C]P943 is a novel, highly selective 5-HT1B PET radioligand. The aim of this study was to determine the test-retest reliability of [(11)C]P943 using two different modeling methods and to perform a power analysis with each quantification technique. Seven healthy volunteers underwent two PET scans on the same day. Regions of interest (ROIs) were the amygdala, hippocampus, pallidum, putamen, insula, frontal, anterior cingulate, parietal, temporal and occipital cortices, and cerebellum. Two multilinear radioligand quantification techniques were used to estimate binding potential: MA1, using arterial input function data, and the second version of the multilinear reference tissue model analysis (MRTM2), using the cerebellum as the reference region. Between-scan percent variability and intraclass correlation coefficients (ICC) were used to assess test-retest reliability. We also performed power analyses to determine the method that would allow the least number of subjects using within-subject or between-subject study designs. A voxel-wise ICC analysis for MRTM2 BPND was performed for the whole brain and all the ROIs studied. Mean percent variability between two scans across regions ranged between 0.4 % and 12.4 % for MA1 BPND, 0.5 % and 11.5 % for MA1 BPP, 16.7 % and 28.3 % for MA1 BPF, and between 0.2 % and 5.4 % for MRTM2 BPND. The power analyses showed a greater number of subjects were required using MA1 BPF compared with other outcome measures for both within-subject and between-subject study designs. ICC values were the highest using MRTM2 BPND and the lowest with MA1 BPF in ten ROIs. Small regions and regions with low binding had lower ICC values than large regions and regions with high binding. Reliable measures of 5-HT1B receptor binding can be obtained using the novel PET radioligand [(11)C]P943. Quantification of 5-HT1B receptor binding with MRTM2 BPND and with MA1 BPP provided the least variability and optimal power for within-subject and between-subject designs.


A Novel Approach for Investigating Upper Airway Hyperresponsiveness Using Micro-CT in Eosinophilic Upper Airway Inflammation such as Allergic Rhinitis Model.
Airway hyperresponsiveness (AHR) has been proposed as a feature of pathogenesis of eosinophilic upper airway inflammation such as allergic rhinitis (AR). The measurement system for upper AHR (UAHR) in rodents is poorly developed, although measurements of nasal resistance have been reported. Here we assessed UAHR by direct measurement of swelling of the nasal mucosa induced by intranasal methacholine (MCh) using micro-computed tomography (micro-CT). Micro-CT analysis was performed in both naïve and ovalbumin-induced AR mice following intranasal administration of MCh. The nasal cavity was segmented into two-dimensional horizontal and axial planes, and the data for nasal mucosa were acquired for the region of interest threshold. Then, a ratio between the nasal mucosa area and nasal cavity area was calculated as nasal mucosa index. Using our novel method, nasal cavity structure was clearly identified on micro-CT, and dose-dependent increased swelling of the nasal mucosa was observed upon MCh treatment. Moreover, the nasal mucosa index was significantly increased in AR mice compared to controls following MCh treatment, while ovalbumin administration did not affect swelling of the nasal mucosa in either group. This UAHR following MCh treatment was completely reversed by pretreatment with glucocorticoids. This novel approach using micro-CT for investigating UAHR reflects a precise assessment system for swelling of the nasal mucosa following MCh treatment; it not only sheds light on the mechanism of AR but also contributes to the development of new therapeutic drugs in AR patients.


Demonstration of optical interference filters utilizing tunable refractive index layers.
Optical interference filters utilizing tunable refractive index layers are shown to have higher spectral fidelity as compared to conventional filters consisting of non-tunable refractive index layers. To demonstrate this increase in spectral fidelity, we design and compare a variety of optical interference filters employing both tunable and non-tunable refractive index layers. Additionally, a five-layer optical interference filter utilizing tunable refractive index layers is designed and fabricated for use with a Xenon lamp to replicate the Air Mass 0 solar irradiance spectrum and is shown to have excellent spectral fidelity.


Global abundance of planktonic heterotrophic protists in the deep ocean.
The dark ocean is one of the largest biomes on Earth, with critical roles in organic matter remineralization and global carbon sequestration. Despite its recognized importance, little is known about some key microbial players, such as the community of heterotrophic protists (HP), which are likely the main consumers of prokaryotic biomass. To investigate this microbial component at a global scale, we determined their abundance and biomass in deepwater column samples from the Malaspina 2010 circumnavigation using a combination of epifluorescence microscopy and flow cytometry. HP were ubiquitously found at all depths investigated down to 4000 m. HP abundances decreased with depth, from an average of 72±19 cells ml(-1) in mesopelagic waters down to 11±1 cells ml(-1) in bathypelagic waters, whereas their total biomass decreased from 280±46 to 50±14 pg C ml(-1). The parameters that better explained the variance of HP abundance were depth and prokaryote abundance, and to lesser extent oxygen concentration. The generally good correlation with prokaryotic abundance suggested active grazing of HP on prokaryotes. On a finer scale, the prokaryote:HP abundance ratio varied at a regional scale, and sites with the highest ratios exhibited a larger contribution of fungi molecular signal. Our study is a step forward towards determining the relationship between HP and their environment, unveiling their importance as players in the dark ocean's microbial food web.


AT2 receptors in cardiovascular and renal diseases.
The renin-angiotensin system (RAS) plays an important role in the initiation and progression of cardiovascular and renal diseases. These actions mediated by AT1 receptor (AT1R) are well established and led to development of selective AT1R blockers (ARBs). In contrast, there is scientific evidence that AT2 receptor (AT2R) mediates effects different from and often opposing those of the AT1R. Meagrely expressed in healthy tissue the AT2R is upregulated in injuries providing an endogenous protection to inflammatory, oxidative and apoptotic processes. Interestingly the beneficial effects mediated by AT2R can be further enhanced by pharmacological intervention using the recently developed AT2R agonists. This review article summarizes our current knowledge about regulation, signalling and effects mediated by AT2R in health and disease, with emphasis on cardiac and renal systems. At the end a novel concept of natural protective systems will be introduced and discussed as an attractive target in drug development.


The Involvement of Intestinal Tryptophan Metabolism in Inflammatory Bowel Disease Identified by a Meta-Analysis of the Transcriptome and a Systematic Review of the Metabolome.
Evidence is emerging for the role of intestinal tryptophan metabolism in the development of inflammatory bowel disease (IBD). In order to identify the role of altered intestinal tryptophan metabolism in IBD pathogenesis, a meta-analysis of the transcriptome was performed to identify differentially expressed genes involved in the tryptophan metabolism pathways in intestinal biopsies of IBD as compared to non-IBD controls. Moreover, a systematic review of the metabolome was performed to identify the concurrent changes in tryptophan metabolites. Integration of the transcriptome and metabolome identified various alterations in intestinal tryptophan metabolism during active disease in IBD patients, including decreased intestinal tryptophan absorption, enhanced kynurenine pathway, increased interstitial serotonin availability, changed indole pathway, and activated aryl hydrocarbon receptor signaling. Therefore, a network of intestinal tryptophan metabolism pathways in IBD could be established, helping to assess the potential of genes and metabolites involved in these pathways as diagnostic markers and targets for IBD management.


Impact of Implementation of "Kayakalp" Initiative on Quality Certification of District Hospitals to National Quality Assurance Standards.
Ministry of Health and Family Welfare has developed National Quality Framework to assess the quality of services for improvement and helps in certification of facilities, while Kayakalp was launched to promote cleanliness and hygiene in public health facilities. The objective of the study is to assess if Kayakalp implementation within the public health facilities supports quality certification of health facilities. A retrospective study was designed to gather data for 32 quality-certified district hospitals under National Quality Assurance Standards (NQAS) between May 2015 and April 2018 by reviewing records. Certification criteria and their external assessment checklist under NQAS and Kayakalp program for district hospitals were extracted from their respective states. External assessment score of all district hospitals under study was entered and analyzed using Statistical Package for the Social Sciences version 22 for Pearson's correlation analysis and MS Excel 2016 for statistical analysis. Pearson's correlation coefficient was 0.217, which means that Kayakalp implementation has less significance on the quality certification of public health facilities to NQAS. A scatter chart was plotted which depicts nonlinear relationship between dependent and independent variable. Overall impact of implementation of Kayakalp initiative on quality certification of public health facilities to NQAS was significantly low; however, this could be due to less weightage given to the checkpoints in NQAS as compared to in NQAS.


An individualized plastic intraoral device for the collection of human parotid saliva.
A new individualized, non-invasive device for the collection of parotid saliva is described which offers the following advantages: automatic placement in the proper position for saliva collection by patients without the help of a technician, lack of deadspace, lack of salivary leakage around the device, elimination of cross contamination between patients, and unlimited re-use. Because of its simplicity, it is an ideal device for routine collection of parotid saliva samples in therapeutic drug monitoring, biochemical monitoring of exposure to toxic materials, and detection of secretory component deficiencies of immune system disorders.


The disappearance of adenosine from blood and platelet suspension in relation to the platelet cyclic AMP content.
Adenosine exerts anti-aggregatory effects on human platelets in vitro, probably by increasing intraplatelet levels of cyclic AMP. In addition, adenosine prevents platelet loss in vivo. We have studied the relationship between the concentration of adenosine in the platelet media and the level of cAMP. In PRP, exogenous adenosine (2-16 microM) was eliminated with a half-life close to 5 min. Approximately half of the added adenosine was deaminated (blocked by 1-2 microM EHNA), and half was eliminated by uptake into platelets (blocked by 2 microM dipyridamole). In whole blood the half-life for adenosine was much shorter, about 15 s. Addition of adenosine deaminase (0.3 microgram ml-1) to PRP resulted in a measured half-life for adenosine approximating that of whole blood. In PRP where adenosine was eliminated as quickly as in whole blood, the adenosine-mediated stimulation of cAMP was 35% lower than in PRP, and the cAMP response lasted 2 min versus 15 min in normal PRP. These results suggest that the magnitude and duration of adenosine's effect on platelets are markedly overestimated by studying platelet suspensions. In blood, the effect of adenosine is smaller in magnitude and very transient. The possibility is discussed that the action of adenosine in vivo on blood platelets can therefore be quite local.


Possible role of calcium in the formation of active extracellular proteinase by Pseudomonas fluorescens.
The requirement for calcium during synthesis of extracellular proteinase by Pseudomonas fluorescens B52 was examined. Synthesis was monitored using cells resuspended at high density in fresh growth medium. Optimum enzyme production was found with cells grown to mid-logarithmic phase in mineral salts medium containing calcium chloride (1.0 mmol/l). Inhibition of synthesis by EDTA addition was rapid, similar to the effect produced by chloramphenicol, an inhibitor of translation. Appearance of enzyme initiated by calcium addition to depleted cells was rapid and was dependent on de novo protein synthesis. Sephadex G-100 chromatography of L-[4,5-3H]leucine-labelled cell-free supernatant liquids revealed that, in the absence of calcium, a low molecular weight (12000-14000 daltons) irreversibly inactive 'precursor' of the proteinase was formed. The results are consistent with the hypothesis that calcium is required for structural integrity of the proteinase as well as for activity.


Concurrent purification of type-1 and type-2A protein phosphatase catalytic subunits.
We describe a simple purification scheme for the active catalytic subunits of both protein phosphatases type-1 and type-2A. The advantage of this procedure over others is that it produces intact proteins with high yield and specific activity and is suitable for either kilograms of tissue or a dish of cells. Type-1 and type-2A phosphatases from rabbit skeletal muscle were resolved on polylysine-agarose and subsequently obtained in homogeneous form. The phosphatases demonstrated characteristic properties. The phosphatase-1 catalytic subunit was inhibited by inhibitor-2 and phosphoinhibitor-1 whereas phosphatase-2A was not. The phosphatase activities were stable for years at -20 degrees C when stored in the presence of Mg2+ and glycerol. Based on the predicted sequence of the carboxyl terminus of each phosphatase, antibodies specific for phosphatases-1 and -2A were produced in rabbits using synthetic peptides as immunogens. Immunoblots showed complete specificity of these antibodies for their respective phosphatases and confirmed that the purified phosphatases has intact carboxyl termini. The purified catalytic subunits and antibodies will be useful for examining the regulation and the physiological roles of these protein phosphatases in cellular physiology.


Solid-solid phase transformation via virtual melting significantly below the melting temperature.
A new phenomenon is theoretically predicted, namely, that solid-solid transformation with a relatively large transformation strain can occur through virtual melting along the interface at temperatures significantly (more than 100 K) below the melting temperature. The energy of elastic stresses, induced by transformation strain, increases the driving force for melting and reduces the melting temperature. Immediately after melting, the stresses relax and the unstable melt solidifies. Fast solidification in a thin layer leads to nanoscale cracking, which does not affect the thermodynamics and kinetics of solid-solid transformation. Seven theoretical predictions are in quantitative agreement with experiments conducted on the beta-->delta transformation in the HMX energetic crystal.


Survival analysis to measure turnover of the medical education workforce in Ethiopia.
Until recently, there were only a few medical schools in Ethiopia. However, currently, in response to the apparent shortage in physician workforce, the country has made huge progress with respect to the expansion of medical schools, by adopting the so-called flooding strategy. Nevertheless, the effectiveness of the intended strategy also relies on physician accessibility and turnover. Therefore, the aim of this study was to examine the distribution of physicians in the medical schools of Ethiopia and to quantify the magnitude and identify factors associated with physician turnover. This organizational faculty physician workforce survey was conducted in seven government-owned medical schools in Ethiopia. Longitudinal medical workforce data set of about 6 years (between September 2009 and June 2015) were retrospectively collected from each of the medical schools. The observation time begins with the date of employment (time zero) and ends at the date on which the physician leaves the appointment/or the data collection date. Kaplan-Meier survival method was used to describe the duration of stay of physicians in the academic health care settings. A Cox proportional hazards (CPH) model was fitted to identify the risk factors for physician turnover. In this study, a total of 1258 faculty physicians were observed in seven medical schools which resulted in 6670.5 physician-years. Of the total, there were 198 (15.7%) turnover events and the remaining 1060 (84.3%) were censored. The average turnover rate is about 29.7 per 1000 physician-years of observations. Multivariate modeling revealed no statistical significant difference in the rate of turnover between males and females (adjusted hazard ratio (AHR), 1.12; 95%CI, 0.71, 1.80). However, a lower rate of physician turnover was observed among those who were born before 1975 (AHR, 0.37; 95%CI, 0.20, 0.69) compared with those who were born after 1985. Physicians with the academic rank of associate professor and above had a lower (AHR, 0.25; 95%CI, 0.11, 0.60) rate of turnover in comparison to lecturers. In addition, physicians working in Jimma University had 1.66 times higher rate of turnover compared with those working in Addis Ababa University. However, the model showed a significantly lower rate of turnover in Mekelle (AHR, 0.16; 95%CI, 0.06, 0.41) and University of Gondar (AHR, 0.46; 95%CI, 0.25, 0.84) compared with that of Addis Ababa. Physician turnover in the remaining medical schools (Bahir Dar, Haromaya, and Hawassa) did not show a statistically significant difference with Addis Ababa University (P > 0.05). This study revealed a strong association between physician turnover with age, academic rank, and workplace. Therefore, the findings of the study have important implications in that attention needs to be given for the needs of faculty physicians and for improving the work environment in order to achieve a high level of retention.


Brain metastasis from transitional cell carcinoma of the bladder--case report.
A rare case of brain metastasis from a transitional cell carcinoma (TCC) of the bladder is presented. A 66-year-old female underwent total removal of a bladder carcinoma and postoperative radiation therapy and chemotherapy. Right hemiparesis and seizures developed about 16 months later, and a solitary brain metastasis was discovered in the left Rolandic area. The tumor was totally removed and microscopic examination showed it to be TCC.


Mouse cytochrome P450 (Cyp3a11): predominant expression in liver and capacity to activate aflatoxin B1.
S1 mapping analysis for the expression of Cyp3a11 and Cyp3a13 indicated that Cyp3a11 mRNA is predominantly expressed in mouse liver, compared with that of Cyp3a13. In addition, all of six inducers, such as dexamethasone, 3-methylcholanthrene, phenobarbital, polychlorinated biphenyl, pregnenolone 16 alpha-carbonitrile, and rifampicin, increased the expression of the Cyp3a11 mRNA more extensively than that of Cyp3a13. The level of mRNAs corresponding to Cyp3a11 and Cyp3a13 reached the maximum level between 4 and 8 weeks after birth. Cyp3a11 enzyme was expressed into CR119 cells which had been established as a cell line stably expressing NADPH-cytochrome P450 reductase cDNA of guinea pigs. These transformants showed aflatoxin B1-dependent cytotoxicity in proportion to the amounts of Cyp3a11 mRNA. This cytotoxicity was enhanced by 7,8-benzoflavone, a known activator of CYP3A protein. Based on these results, we confirm that CYP3A in the mouse, which is an animal species known to be relatively insensitive to aflatoxin B1 genotoxicity, can activate this mycotoxin efficiently.


Isolation of Encephalitozoon cuniculi from urine samples.
Encephalitozoon cuniculi was isolated from the urine of infected rabbits using human and canine tissue cultures. The organism was isolated from 7 of 11 contaminated urines from seropositive animals. The advantages of urine over tissue as a source of E. cuniculi are that it is obtainable from living animals, can be examined for the presence of organisms, and is essentially free of cells likely to overgrow the tissue cultures used for isolation.


[Pain therapy and depression in cancer patients].
In a pilot study involving eleven terminal tumor patients suffering pain, the effect of monotherapy with oral, slow-release morphine on analgesia, somatogenic components, depression and state of psychic health was investigated. A significant decrease in pain intensity was observed. A significant correlation was found between analgesia and changes in depression. Individual assessment on the basis for the Hamilton Depression Scale revealed a significant association between the treatment of pain and sleep disturbances, depressive states, restlessness and suicidality. In addition, analgesia led to an improvement in general psychic health as indicated by the v. Zerssen scale. A reactive-depressive symptomatology in tumor patients suffering pain can be positively influenced by selective opiate therapy.


Acute hepatitis in a piglet experimentally inoculated with tissue homogenates from pigs with postweaning multisystemic wasting syndrome.
Five 2 day-old colostrum-deprived piglets were inoculated with tissue homogenates from pigs with postweaning multisystemic wasting syndrome. One of the five piglets developed icterus and died 23 days post-inoculation. Histologic examination revealed acute hepatitis. Porcine circovirus type 2 (PCV-2) antigen and nucleic acid were detected in hepatocytes and phagocytic cells. Ultrastructurally, hepatocytes and phagocytic cells had large numbers of cytoplasmic inclusions, which were composed of electron-dense paracrystalline arrays of small non-enveloped viral particles approximately 17 nm in diameter. Apoptotic hepatocytes were confirmed by the TUNEL method and electron microscopic examination. These findings may indicate that hepatocellular necrosis is associated with replication of PCV-2. Apoptosis of hepatocytes also contributes to the pathogenesis of hepatic lesions in this case.


Structural bases of the redox-dependent conformational switch in the serpin PAI-2.
Depending on the redox-status, the serpin plasminogen activator inhibitor type 2 (PAI-2) can exist in either a stable monomeric or polymerogenic form. The latter form, which spontaneously forms loop-sheet polymers, has an open beta-sheet A and is stabilized by a disulfide bond between C79 (in the CD-loop) and C161 (at the bottom of PAI-2). Reduction of this bond results in a closing of the beta-sheet A and converts PAI-2 to a stable monomeric form. Here we show that the stable monomeric and polymerogenic forms of PAI-2 are fully interconvertible, depending on redox-status of the environment. Our intramolecular distance measurements indicate that the CD-loop folds mainly on one side of the stable monomeric form of the inhibitor. However, the loop can translocate about 54A to the bottom of PAI-2 so that the C79-C161 disulfide bond can form under oxidizing conditions. We show also that the redox-active C79 can form a disulfide-link to the matrix protein vitronectin, suggesting that vitronectin can stabilize active PAI-2 in extracellular compartments. PAI-2 is therefore a rare example of a redox-sensitive protein for which the activity and polymerization ability are regulated by reversible disulfide bond formation leading to major translocation of a loop and significant conformational changes in the molecule.


Risk factors for visceral leishmaniasis relapse in immunocompetent patients following treatment with 20 mg/kg liposomal amphotericin B (Ambisome) in Bihar, India.
A proportion of all immunocompetent patients treated for visceral leishmaniasis (VL) are known to relapse; however, the risk factors for relapse are not well understood. With the support of the Rajendra Memorial Research Institute (RMRI), Médecins Sans Frontières (MSF) implemented a program in Bihar, India, using intravenous liposomal amphotericin B (Ambisome) as a first-line treatment for VL. The aim of this study was to identify risk factors for VL relapse by examining the characteristics of immunocompetent patients who relapsed following this regimen. This is an observational retrospective cohort study of all VL patients treated by the MSF program from July 2007 to August 2012. Intravenous Ambisome was administered to 8749 patients with VL in four doses of 5 mg/kg (for a total dose of 20 mg/kg) over 4-10 days, depending on the severity of disease. Out of 8588 patients not known to be HIV-positive, 8537 (99.4%) were discharged as initial cures, 24 (0.3%) defaulted, and 27 (0.3%) died during or immediately after treatment. In total, 1.4% (n = 119) of the initial cured patients re-attended the programme with parasitologically confirmed VL relapse, with a median time to relapse of 10.1 months. Male sex, age <5 years and ≥45 years, a decrease in spleen size at time of discharge of ≤0.5 cm/day, and a shorter duration of symptoms prior to seeking treatment were significantly associated with relapse. Spleen size at admission, hemoglobin level, nutritional status, and previous history of relapse were not associated with relapse. This is the largest cohort of VL patients treated with Ambisome worldwide. The risk factors for relapse included male sex, age <5 and ≥45 years, a smaller decrease in splenomegaly at discharge, and a shorter duration of symptoms prior to seeking treatment. The majority of relapses in this cohort occurred 6-12 months following treatment, suggesting that a 1-year follow-up is appropriate in future studies.


Knee bobbing in Charcot-Marie-Tooth disease.
Patients with Charcot-Marie-Tooth (CMT) disease most commonly have a slowly progressive neuropathy where ankle dorsiflexion weakness is much more prominent than ankle plantar flexion weakness. The eventual involvement of the ankle plantar flexors has major functional consequences for patients as they lose the ability to stand still. We have found the knee bob sign whereby both knees bob up and down when standing still to be a reliable marker of ankle plantar flexion weakness in CMT.


Phylogeny based on two mtDNA genes (Co-1, Cyt-B) among Sculpins (Scorpaeniformes, Cottidae) and some other scorpionfish in the Russian Far East.
The average scores of p-distances at Co-1 and Cyt-b genes revealed a pattern of increased nucleotide diversity for four categories: (1) intraspecies, (2) intragenus, (3) intrafamily, and (4) intraorder. Scores for Co-1 genes were following: (1) 0.24 ± 0.19% (n = 66), (2) 1.54 ± 0.27% (n = 33), (3) 11.57 ± 0.24% (n = 42), and (4) 12.91 ± 0.16% (n = 102); while for Cyt-b genes, those values were (1) 1.92 ± 0.55% (n = 24), (2) 8.19 ± 0.09% (n = 812), (3) 15.42 ± 0.07% (n = 1573), and (4) 23.13 ± 0.19% (n = 211). A concordant increase in the distance score, as the rank of taxa grows, with the minimum at intraspecies level substantiates the concept that speciation in the order Scorpaeniformes mostly follows a geographic mode. Phylogenetic trees for 40 sequences of scorpionfish and four other fishes belonging to Actinopterigii were developed using Co-1 gene and four different analytical approaches: Bayesian, ML, MP, and NJ. Resolution of the Co-1 trees for the three genera that included different species branches was quite distinct in all approaches. Intrafamily branching for Cyt-b in Cottidae was also supported by all four kinds of trees but only for less numerous genera in the research.


Treatment of Peri-implantitis Using a Combined Decontaminative and Regenerative Protocol: Case Report.
Peri-implantitis is a long-term complication that frequently occurs after implant surgery. Several treatment methods have been proposed that are aimed at arresting the disease and potentially regenerating bone defects related to it. The use of a combination of proposed decontaminative treatments could possibly improve outcomes. In this case report the authors describe a combined mixed protocol, in which chemical decontamination and a laser-assisted decontamination technique are used in a surgical regenerative approach to successfully manage and treat a case of peri-implantitis. The combined surgical and antimicrobial protocol described can be a suitable treatment option in cases in which implants show severe bone resorption as a result of peri-implant disease.


Childhood tuberculosis and human immunodeficiency virus status in Brazil: a hierarchical analysis.
Human immunodeficiency virus (HIV) infection may impact tuberculosis (TB) diagnosis, clinical presentation and treatment outcomes in children as the signs and symptoms of both diseases overlap. To compare the sociodemographic and clinical profiles of childhood TB according to HIV status in Brazil. This was a cross-sectional study of data on subjects aged <15 years retrieved from the Brazilian National Electronic Disease Registry (Sistema de Informação de Agravos de Notificação) database on TB to compare TB-HIV coinfected patients and patients with TB only registered between 2007 and 2011. A hierarchical logistic regression model was applied. Of 6091 cases analysed, 780 (12%) were TB-HIV patients, while 5311 (87%) presented with TB only. TB-HIV patients were more likely to be institutionalised (OR 2.22, 95%CI 1.43-3.46), to present with relapsed TB (OR 5.03, 95%CI 2.02-12.5) and be readmitted after treatment default (OR 16.7, 95%CI 4.34-64.46). They were also more likely to have unfavourable outcomes, including default (OR 2.85, 95%CI 1.81-4.49), death due to TB (OR 2.76, 95%CI 1.27-6.03) and death from other causes (OR 5.59, 95%CI 2.63-11.8). Our study highlights the challenges of using national registers for research into childhood TB.


Activity of newer fluoroquinolones against gram-positive and gram-negative bacteria isolated from ocular infections: an in vitro comparison.
To determine the antibacterial activity of newer fluoroquinolones and compare their activity between ciprofloxacin-susceptible and resistant bacterial isolates from patients with keratitis and endophthalmitis. The minimum inhibitory concentration (MIC) of ciprofloxacin, ofloxacin, levofloxacin, gatifloxacin and moxifloxacin was determined for 123 bacterial isolates, using E test. Among the 123 isolates, 68 were gram-positive (Staphylococcus spp, Streptococcus spp, Corynebacterium spp, Bacillus spp.) and 55 were gram-negative (Pseudomonas aeruginosa). The bacterial isolates were divided into three groups: susceptible/intermediate/resistant to ciprofloxacin. The MIC values for various fluoroquinolones were compared between the three groups and between gram-positive and gram-negative bacteria. For gram-positive isolates, median MICs of fourth generation fluoroquinolones were lower than second generation. The median MIC was lowest for gatifloxacin and moxifloxacin (0.094 mg/ml) in ciprofloxacin-susceptible isolates of gram-positive bacteria. For ciprofloxacin-susceptible gram-negative bacteria, the median MIC of ciprofloxacin (0.19 mg/ml) was significantly lower than ofloxacin, levofloxacin, gatifloxacin and moxifloxacin (1.5, 0.5, 0.5 and 2 mg/ml respectively). Ciprofloxacin-resistant isolates of gram-positive bacteria showed higher MIC of levofloxacin, moxifloxacin and gatifloxacin though they remained susceptible to them. None of the fluoroquinolones were effective against ciprofloxacin-resistant gram-negative bacteria. Overall, for gram-positive bacteria, median MICs of levofloxacin, moxifloxacin and gatifloxacin were below ciprofloxacin, the MIC of gatifloxacin and moxifloxacin was equal for gram-positive bacteria. Levofloxacin, gatifloxacin and moxifloxacin are statistically more effective against gram-positive bacteria, the latter two being equally effective. Ciprofloxacin remains the most effective fluoroquinolone against gram-negative bacteria.


Sequence-based diagnosis of tyrosinase-related oculocutaneous albinism: successful sequence analysis of the tyrosinase gene from blood spots dried on filter paper.
A large number of mutations of the tyrosinase gene result in oculocutaneous albinism (OCA). Therefore, at present, sequence analysis of the tyrosinase gene has become necessary to diagnose OCA patients and their relatives. The aim of this study was to facilitate the sequence-based diagnosis of tyrosinase-related OCA by using small amounts of the patient's blood. Blood spots dried on filter papers were used as sources of genomic DNA. The exons and flanking regions of the tyrosinase gene were amplified by polymerase chain reaction (PCR) and were directly sequenced in both directions. We successfully amplified all exons of the tyrosinase gene by PCR and were able to characterize compound heterozygous mutations of R278X and + delta C310 in the patient's gene. Recent advances of PCR-related technology allowed us to use fairly limited samples of blood for sequence analysis of the tyrosinase gene.


Poleward shifts and altered periodicity in boreal bird irruptions over six decades.
Range boundaries are long-term biogeographic features of species distributions and abundance. However, many species demonstrate dynamic range boundaries, reflecting strong seasonal and annual variability in migratory behaviour. As a form of facultative migration, irruptions involve the movement of many individuals outside of their resident range in response to climate variability, resource availability, and demographic processes. Many species have experienced range shifts and altered phenology in response to modern climate change, but spatiotemporal changes in irruption dynamics are less well known. We quantified changes in the geography and periodicity of boreal bird irruptions across eastern North America from 1960 to 2021. Using data from Audubon's Christmas Bird Count for nine finch species, including several exhibiting recent population declines, we evaluated latitudinal trends in southern range and irruption boundaries and characterized irruption periodicity using spectral wavelet analysis. Six boreal birds exhibited significant northward shifts in their southern range boundaries and three species displayed shifts in their southern irruption boundaries. Irruption periodicity across multiple species was consistent across the 1960s and 1970s, culminating in frequent and synchronized irruptions of multiple species (superflights) during earlier decades. Coherence between species dampened beginning in the early 1980s as superflight periodicity became increasingly unstructured, finally reforming in recent decades, after 2000. Boreal birds are considered important sentinels of the boreal forests, and northward shifts and altered periodicity of irruptions may indicate broad-scale changes in climate- and resource-associated drivers operating across the boreal forests.


Feedback regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase in Saccharomyces cerevisiae.
In eukaryotic cells all isoprenoids are synthesized from a common precursor, mevalonate. The formation of mevalonate from 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) is catalyzed by HMG-CoA reductase and is the first committed step in isoprenoid biosynthesis. In mammalian cells, synthesis of HMG-CoA reductase is subject to feedback regulation at multiple molecular levels. We examined the state of feedback regulation of the synthesis of the HMG-CoA reductase isozyme encoded by the yeast gene HMG1 to examine the generality of this regulatory pattern. In yeast, synthesis of Hmg1p was subject to feedback regulation. This regulation of HMG-CoA reductase synthesis was independent of any change in the level of HMG1 mRNA. Furthermore, regulation of Hmg1p synthesis was keyed to the level of a nonsterol product of the mevalonate pathway. Manipulations of endogenous levels of several isoprenoid intermediates, either pharmacologically or genetically, suggested that mevalonate levels may control the synthesis of Hmg1p through effects on translation.


Synthesis, Structures, and Proton Self-Exchange Reaction of μ3-Oxido/Hydroxido Bridged Trinuclear Uranyl(VI) Complexes with Tridentate Schiff-Base Ligands.
New μ3-hydroxido/oxido bridged trinuclear uranyl(VI) complexes with 3,5-di-t-butyl-N-salicylidene-2-aminophenolato (dbusap2-) ligands, Et3NH[(UO2)3(μ3-OH)(dbusap)3] (Et3NH[1]) and (Et3NH)2[(UO2)3(μ3-O)(dbusap)3] ((Et3NH)2[2]) were synthesized and characterized. Single-crystal X-ray structures of both complexes were determined. The oxygen atom on μ3-hydroxido center in [1]- is sp3 hybridized with an average U-(μ3-O)-U bond angle of 109.7(5)°; the μ3-oxido atom in [2]2- is sp2 hybridized with an average U-(μ3-O)-U bond angle of 118.0(10)°. U-(μ3-O) distances in [1]- are long (average of 2.43(1) Å) compared with those in [2]2- (average of 2.23(2) Å). The optimized geometries of the [(UO2)3(μ3-OH)]5+ core in [(UO2)3(μ3-OH)(sap)3]- and the [(UO2)3(μ3-O)]4+ core in [(UO2)3(μ3-O)(sap)3]2- (where sap = N-salicylidene-2-aminophenolato) from density functional theory (DFT) calculations resemble those in [1]- and [2]2-, respectively. The U-(μ3-O) bond in [2]2- is significantly shorter than that in [1]-, because of the greater negative charge on the central μ3-oxido. A reversible structural conversion between [2]2- and [1]- was conducted by protonation and deprotonation of the μ3-oxido/hydroxido group. The activation enthalpy and entropy of the proton self-exchange reaction between [1]- and [2]2- determined from the temperature dependence of 1H NMR coalescence are ΔH⧧ = 23 ± 2 kJ mol-1 and ΔS⧧ = -77 ± 5 J K-1 mol-1.


Trypsin binding activity of alpha 2-macroglobulin in cystic fibrosis and other lung diseases.
Abnormalities of the interaction between alpha 2-macroglobulin and proteases have been suspected in cystic fibrosis. We measured the binding activity for trypsin of alpha 2-macroglobulin in 65 patients with cystic fibrosis, 41 obligate heterozygotes for cystic fibrosis, 18 children with asthma, 21 adult patients with chronic obstructive pulmonary disease, and 21 healthy control subjects. The assay was based on the observation that, once it is bound to alpha 2-macroglobulin, trypsin is no longer inhibited by soybean trypsin inhibitor. The bound trypsin retains activity against synthetic substrates such as N-alpha-benzoyl-arginine-p-nitroanilide. We found a moderately increased molar binding ratio of trypsin to alpha 2-macroglobulin in all patient groups and heterozygotes compared to healthy control subjects. The absolute concentration of alpha 1-macroglobulin was related to age rather than to the disease of the patient. Our data argue against a defect in protease-binding activity of alpha 2-macroglobulin in cystic fibrosis. The moderately increased binding activity observed could have been related to a structural difference in alpha 2-macroglobulin or to binding of ligands. This finding however, was not unique to patients with cystic fibrosis; the binding activity was increased in heterozygotes and in patients with other pulmonary diseases.


Patrinia scabiosaefolia inhibits the proliferation of colorectal cancer in vitro and in vivo via G1/S cell cycle arrest.
Patrinia scabiosaefolia (PS) has long been used as an important component in traditional Chinese medicine formulas to treat gastrointestinal malignancies including colorectal cancer (CRC). We recently reported that PS can inhibit CRC growth through induction of apoptosis and inhibition of tumor angiogenesis. To further elucidate the mode of action of PS, in the present study, we used a CRC mouse xenograft model and a human CRC cell line HT-29 to evaluate the effect of the ethanol extract of PS (EEPS) on cancer cell proliferation and investigated the underlying molecular mechanisms. We found that EEPS inhibited CRC growth both in vivo and in vitro, which was associated with the inhibitory effects of EEPS on cancer cell proliferation. In addition, EEPS treatment significantly blocked G1 to S phase cell cycle progression in HT-29 cells. Moreover, EEPS treatment decreased the expression of pro-proliferative CyclinD1 and CDK4, at both the mRNA and protein levels. Thus, inhibition of cell proliferation via G1/S cell cycle arrest might be a potential mechanism whereby PS effectively treats cancers.


Autophagy: machinery and regulation.
Macroautophagy/autophagy is an evolutionarily conserved cellular degradation process that targets cytoplasmic materials including cytosol, macromolecules and unwanted organelles. The discovery and analysis of autophagy-related (Atg) proteins have unveiled much of the machinery of autophagosome formation. Although initially autophagy was regarded as a survival response to stress, recent studies have revealed its significance in cellular and organismal homeostasis, development and immunity. Autophagic dysfunction and dysregulation are implicated in various diseases. In this review, we briefly summarize the physiological roles, molecular mechanism, regulatory network, and pathophysiological roles of autophagy.


UV light-induced crosslinking of the strands of poly(dA-dT) and related alternating purine-pyrimidine DNAs.
Alkaline agarose gel electrophoresis was used to detect UV-induced crosslinking of the strands of poly(dA-dT) and related alternating purine-pyrimidine DNAs in solutions stabilizing various polynucleotide conformations. Strands of the B-form and A-form of poly(dA-dT) were not crosslinked but a UV dose-dependent retarded species appeared in the denaturing gels in parallel with the polynucleotide isomerization into the unusual X-form. Most other polynucleotides adopting the X-form were crosslinked as well. The exceptions include the X-forms of poly(dA-butyl5dU) and poly(dA-pentyl5dU) whose strands do not crosslink because the long exocyclic substituents attached to uracil make the photodimerization impossible. Strands of poly(amino2dA-dT) and poly(dA, amino2dA-dT), the latter polynucleotide containing roughly equal amounts of amino2adenine and adenine, also do not crosslink upon UV irradiation because they isomerize into an A-like conformation which is different from the X-form of poly (dA-dT). In contrast, strands of the mixed copolymers of poly(dA, amino2dA-dT) containing low amino2adenine contents are crosslinked upon UV irradiation, in accordance with the observation that they isomerize into the X-form.


Measuring Housing Stability With Consumer Reference Data.
Housing instability for low-income renters has drawn greater attention recently, but measurement has limited research on policies to stabilize housing. Address histories from consumer reference data can be used to increase the quantity and quality of research on low-income renters. Consumer data track housing moves throughout the entire United States for most of the adult population. In this article, I show that such data can measure housing stability for groups with very low income and extreme instability. For example, the data can track housing moves during natural disasters, at demolition of public housing, for households at high risk of homelessness, and during gentrification. Consumer data can track housing instability outcomes that are more common than shelter entry and less expensive to collect than surveys. Relative to existing administrative address histories, consumer data allow researchers to track housing moves to exact addresses and across jurisdictions.


Resonant population cycles in temporally fluctuating habitats.
Experiments with the flour beetle Tribolium have revealed that animal numbers were larger in cultures grown in a periodically fluctuating volume of medium than in cultures grown in a constant volume of the same average size. In this paper we derive and analyze a discrete stage-structured mathematical model that explains this phenomenon as a kind of resonance effect. Habitat volume is incorporated into the model by the assumption that all rates of cannibalism (larvae on eggs, adults on eggs and pupae) are inversely proportional to the volume of the culture medium. We tested this modeling assumption by conducting and statistically analyzing laboratory experiments. For parameter estimates derived from experimental data, our model indeed predicts, under certain circumstances, a larger (cycle-average) total population abundance when the habitat volume periodically fluctuates than when the habitat volume is held constant at the average volume. The model also correctly predicts certain phase relationships and transient dynamics observed in data. The analyses involve a thorough integration of mathematics, statistical methods, biological details and experimental data.


The enhanced aerosol performance of salbutamol from dry powders containing engineered mannitol as excipient.
The aim of the present study was to investigate the effect of crystallising mannitol from different binary mixtures of acetone/water on the resultant physical properties and to determine the effects of any changes on in vitro aerosolisation performance, when the different mannitol crystals were used as a carrier in dry powder inhaler formulations containing salbutamol sulphate. Mannitol particles were crystallised under controlled conditions by dissolving the sugar in water and precipitating the sugar using binary mixtures of acetone/water in different percentages as anti-solvent media. For comparison purposes the physical properties and deposition behaviour of commercially available mannitol were also studied. SEM showed that all crystallised mannitol particles were more elongated than the commercial mannitol. Solid state studies revealed that commercial mannitol and mannitol crystallised using acetone in the presence of 10-25% v/v water as anti-solvent was beta-polymorphic form whereas mannitol crystallised in the presence of a small amount of water (0-7.5%) was the alpha-form. All the crystallised mannitol samples showed poor flowability. Nevertheless, the powdered crystallised mannitol and commercial samples were blended with salbutamol in the ratio 67.5:1. The aerosolisation performance of the formulations containing the engineered mannitol (evaluated using Multi Stage Liquid Impinger) was considerably better than that of the commercial mannitol formulation (the fine particle fraction was increased from 15.42% to 33.07-43.99%, for the formulations containing crystallised mannitol). Generally, carriers having a high tapped density and high fraction of fine carrier particles produced a high FPF. The improvement in the DPI performance could be attributed to the presence of elongated carrier particles with smooth surfaces since these are believed to have less adhesive forces between carrier and the drug resulting in easier detachment of the drug during the inhalation.


Pathways responsible for platelet hypersensitivity in rats with diabetes. II. Spontaneous diabetes in BB Wistar rats.
The discovery of a group of spontaneously diabetic rats has made it possible to examine changes in diabetic animals in the absence of possible confounding toxic effects of diabetogenic agents. The responses of washed platelets to adenosine diphosphate (ADP), thrombin, or collagen have been compared with platelets from spontaneously diabetic rats (these rats were hyperglycemic), their nondiabetic littermates (normoglycemic), and control rats from the same colony. Platelets from the diabetic rats aggregated more extensively in response to ADP than did platelets from the nondiabetic littermates or control animals. In contrast, platelet aggregation and release of granule contents in response to a low thrombin concentration (0.05 U/ml) were greater with platelets from diabetic rats and nondiabetic littermates than with platelets from control rats. A similar effect of collagen on the release of platelet serotonin was observed. Except at low concentrations of thrombin, the enhanced sensitivity to thrombin-induced aggregation and release of granule contents from platelets from diabetic rats or their nondiabetic littermates could not be inhibited by creatine phosphate-creatine phosphokinase (CP/CPK) and aspirin (CP/CPK used at concentrations that inhibited aggregation induced by ADP [10 mumol/L] and aspirin at concentrations that inhibited thromboxane B2 production induced by thrombin [1 U/ml] by 99%). Loss of radioactivity from platelets labeled with 3H-arachidonic acid and the amount of thromboxane B2 formed in response to high concentrations of thrombin (1 U/ml) was greater from platelets from the diabetic rats or their nondiabetic littermates than from control animals. Thus the effect of diabetes on this aspect of arachidonate metabolism is not primarily determined by blood glucose levels.(ABSTRACT TRUNCATED AT 250 WORDS)


Imaging features of colovesical fistulae on MRI.
MRI is routinely used in the investigation of colovesical fistulae at our institute. Several papers have alluded to its usefulness in achieving the diagnosis; however, there is a paucity of literature on its imaging findings. Our objective was to quantify the MRI characteristics of these fistulae. We selected all cases over a 4-year period with a final clinical diagnosis of colovesical fistula which had been investigated with MRI. The MRI scans were reviewed in a consensus fashion by two consultant uroradiologists. Their MRI features were quantified. There were 40 cases of colovesical fistulae. On MRI, the fistula morphology consistently fell into three patterns. The most common pattern (71%) demonstrated an intervening abscess between the bowel wall and bladder wall. The second pattern (15%) had a visible track between the affected bowel and bladder. The third pattern (13%) was a complete loss of fat plane between the affected bladder and bowel wall. MRI correctly determined the underlying aetiology in 63% of cases. MRI is a useful imaging modality in the diagnosis of colovesical fistulae. The fistulae appear to have three characteristic morphological patterns that may aid future diagnoses of colovesical fistulae. To the authors' knowledge, this is the first publication of the MRI findings in colovesical fistulae.


Using Pupillometry to Investigate Sentence Comprehension in Children With and Without Specific Language Impairment.
In this study pupillometry was used to investigate the allocation of attentional resources associated with sentence comprehension in children with and without specific language impairment (SLI). Eighteen children with SLI (age: M = 6.4 years) and 18 typically developing (TD) children (age: M = 6.3 years) participated in the study. A sentence comprehension task was presented that comprised items designated as easy or hard. Easy sentences contained 4 or 5 words, and hard sentences contained 6 or 7 words. For the TD group, pupil size was significantly larger when comprehending hard sentences compared with easy sentences. There was no effect of sentence difficulty on pupil size in the SLI group. Comparisons between groups revealed pupil sizes for the SLI group were significantly larger than those for the TD group for easy sentences. There were no group differences for the hard sentences. In TD children, pupillometry was sensitive to the attentional demands associated with sentence comprehension. Between-subjects comparisons indicated that the TD group allocated less attention than did the children with SLI for the easy sentences but not for the hard sentences. This study provides evidence of attentional differences between children with SLI and TD children under conditions of low processing demands.


Protein synthesis studies in skeletal muscle of aging rats. II. In vitro studies with 0.5M potassium chloride washed polyribosomes.
To investigate further the age-related reduction in muscle protein synthesis activity found previously using a crude polyribosome/pH 5 system (Pluskal et al., 1984), a 0.5M KCl washing procedure was utilized to remove the nonribosomal factors from polyribosomes isolated from male Sprague-Dawley rats in the following age groups: young (1 to 2 months), mature (12 months), and aged (22 to 24 months). Using a common source of enriched elongation factor fraction from young animals, it was not possible to demonstrate any significant difference (p greater than .05) in protein synthesis between the 0.5M KCl-washed polyribosomes isolated from the various age groups. Using a cell-free system containing young salt washed polyribosomes stimulated by the addition of 0.5M KCl-wash fractions, however, it was shown that the mature and aged salt-wash fractions were less (p less than .05) active than material from young animals. Thus, the observed decline in protein synthesis efficiency during aging may be attributed to a reduced capacity to promote initiation/elongation by the nonribosomal salt wash fractions of muscle polyribosomes.


[The effectiveness of FID-CT (functional image of dynamic CT) for the evaluation of early cerebral ischemia].
A computer program was newly developed to display the ischemic area from the serial dynamic CT scan, namely the functional image of the dynamic CT (FID-CT). The principles of FID-CT are as follows; Seven rapid-sequence dynamic CT scans were taken following a peripheral bolus intravenous injection of 40 ml of iopamidol. As the data from each scan can be separated into three consecutive segments, we obtained 21 images during 44 seconds. Time density curves of each pixel were calculated employing Gamma variate fitting method. Eight functional parameters obtained from this curve were displayed with gray-scale pixel by pixel. These eight images were functional images obtained from dynamic CT. Only three or four minutes were required to complete all the calculations. Twenty-two patients were examined with both FID-CT and 123I-SPECT. In each case, the lesion detected by FID-CT was remarkably consistent with that shown by SPECT. Two representative cases were presented. The authors believe that FID-CT is a very useful diagnostic method in the acute stage of cerebral ischemia because the method can be quickly and easily performed and it discloses the ischemic area with fair certainty.


Effect of Metoprolol Succinate in Patients with Stable Angina and Elevated Heart Rate Receiving Low-Dose β-Blocker Therapy.
Aims: β-blockers are underused in Chinese patients with coronary heart disease. The prescribed dose is often low. The aim of this study was to investigate the effect of metoprolol succinate doses of 95 mg and 190 mg on heart rate (HR) control, as well as drug tolerance, in Chinese patients with stable angina, low-dose β-blocker use and unsatisfactory HR control. Methods: This was a multicenter, randomized, open-label, parallel-group trial in 15 clinical sites. Patients with stable angina, taking low-dose β-blockers (equivalent to metoprolol succinate 23.75-47.5 mg/day), and having a resting HR of ≥ 65 bpm were enrolled and randomized to either the metoprolol 95-mg group or the 190-mg group. The change in 24-h average HR from baseline recorded by Holter monitoring and the percentages of patients with resting HR controlled to ≤ 60 bpm were compared between the two groups. Results: Two hundred thirty-one patients entered the intent-to-treat population for the main analysis. The change in 24-h average HR from baseline was -0.62 ± 0.66 bpm in the 95 mg group and -2.99 ± 0.62 bpm in the 190 mg group (p = 0.0077) after 8 weeks of treatment. The percentages of patients with resting HR controlled to ≤ 60 bpm were 24.1% (95% CI: 16.35%, 31.93%) and 40.0% (95% CI: 31.05%, 48.95%), respectively (p = 0.0019). Only 4 and 2 of the patients, respectively, discontinued the study drugs because of hypotension or bradycardia. Conclusions: The metoprolol succinate dose of 190 mg is superior to the 95 mg dose in terms of HR control, in Chinese patients with stable angina, low-dose β-blocker use and unsatisfactory HR control. Both doses were well tolerated.


Identification and validation of a Schistosoma japonicum U6 promoter.
RNA polymerase III promoters have been widely used to express short hairpin-RNA (shRNA), microRNA (miRNA), and small guide RNA (sgRNA) in gene functional analysis in a variety of organisms including Schistosoma mansoni. However, no endogenous RNA polymerase III promoters have been identified in Schistosoma japonicum. The lack of appropriate promoters in S. japonicum has hindered its gene functional analysis. Identification of functional promoters in S. japonicum is therefore in urgent need. Via sequence alignment, a 347 bp sequence upstream from the coding region of S. japonicum U6 small nuclear RNA (snRNA) was identified, cloned, and named as S. japonicum U6 (sjU6) promoter. A sgRNA sequence named as sgRNA970 was designed, and its Cas9 nuclease guiding activity was confirmed by in vitro cleavage assay. The sjU6 promoter was ligated with sgRNA970 coding sequence by overlap PCR to generate a sjU6-sgRNA970 expression cassette. The expression cassette was inserted into a lentiviral plasmid to construct the pHBLV-sgRNA970 plasmid. First, we tested the sjU6 promoter activity in HEK293 cells by transfecting HEK293 cells with the pHBLV-sgRNA970 plasmid. RT-PCR amplification of the total RNA from the transfected HEK293 cells confirmed the presence of sgRNA970 transcript and indicated sjU6 promoter was functional to initiate transcription in HEK293 cells. Then we transduced the lentivirus expressing Cas9-ZsGreen fusion protein into 14 dpi schistosomula to test whether lentivirus was capable to induce exogenous gene expression in S. japonicum. Fluorescence microscopy and western blot results confirmed the expression of Cas9-ZsGreen fusion protein in S. japonicum. Therefore, this lentiviral system was adapted to test promoter activity in S. japonicum. Finally, we transduced 14 dpi S. japonicum with lentivirus produced from the pHBLV-sgRNA970 plasmid. RT-PCR amplification of the total RNA from transduced schistosomula confirmed the presence of sgRNA970 transcript and therefore indicated sjU6 promoter was functional to initiate transcription in S. japonicum. To our knowledge, sjU6 promoter would be the first identified and validated endogenous RNA polymerase III promoter in S. japonicum, which could be used for future CRISPR/Cas9 studies in S. japonicum.


Human Immunodeficiency Virus Transmission Risk in Analytical Treatment Interruption Studies: Relational Factors and Moral Responsibility.
Analytical treatment interruption (ATI) is becoming common in human immunodeficiency virus (HIV) cure-related research, but its use is controversial. ATI raises concerns about risks of HIV transmission to sexual partners of study participants. Researchers may have difficulty addressing these risks, given that study participants' private behavior is implicated, the partners are not enrolled in the research, and behavioral HIV risk mitigation strategies usually fall outside the study objectives. This analysis argues that researchers should assume some responsibility for partners' risks, based on the importance of partner relationships for the study participants themselves, and out of concern for the partners' welfare. Adding this responsibility is reasonable since the risk is created in part by research procedures, and since concern for third parties is often part of professional standards for healthcare providers. Study participants and their partners also bear some responsibility. Specific recommendations for measures to address risk are discussed.