Danger Changes the Way the Brain Consolidates Neutral Information; and Does So by Interacting with Processes Involved in the Encoding of That Information.
This study examined the effect of danger on consolidation of neutral information in two regions of the rat (male and female) medial temporal lobe: the perirhinal cortex (PRh) and basolateral amygdala complex (BLA). The neutral information was the association that forms between an auditory stimulus and a visual stimulus (labeled S2 and S1) across their pairings in sensory preconditioning. We show that, when the sensory preconditioning session is followed by a shocked context exposure, the danger shifts consolidation of the S2-S1 association from the PRh to the BLA; and does so by interacting with processes involved in encoding of the S2-S1 pairings. Specifically, we show that the initial S2-S1 pairing in sensory preconditioning is encoded in the BLA and not the PRh; whereas the later S2-S1 pairings are encoded in the PRh and not the BLA. When the sensory preconditioning session is followed by a context alone exposure, the BLA-dependent trace of the early S2-S1 pairings decays and the PRh-dependent trace of the later S2-S1 pairings is consolidated in memory. However, when the sensory preconditioning session is followed by a shocked context exposure, the PRh-dependent trace of the later S2-S1 pairings is suppressed and the BLA-dependent trace of the initial S2-S1 pairing is consolidated in memory. These findings are discussed with respect to mutually inhibitory interactions between the PRh and BLA, and the way that these regions support memory in other protocols, including recognition memory in people.SIGNIFICANCE STATEMENT The perirhinal cortex (PRh) and basolateral amygdala complex (BLA) process the pairings of neutral auditory and visual stimuli in sensory preconditioning. The involvement of each region in this processing is determined by the novelty/familiarity of the stimuli as well as events that occur immediately after the preconditioning session. Novel stimuli are represented in the BLA; however, as these stimuli are repeatedly presented without consequence, they come to be represented in the PRh. Whether the BLA- or PRh-dependent representation is consolidated in memory depends on what happens next. When nothing of significance occurs, the PRh-dependent representation is consolidated and the BLA-dependent representation decays; but when danger is encountered, the PRh-dependent representation is inhibited and the BLA-dependent representation is selected for consolidation.


Two new genera and two new species of eriophyoid mites (Acari: Eriophyoidea) from North Bengal, India.
Two new genera and two new species of eriophyoid mites viz., Propeaciota genusetosis n. gen. and n. sp. infesting Acer sp. (Aceraceae) and Spinaephyes alnus n. gen. and n. sp. infesting Alnus nepalensis D. Don (Betulaceae) are described in the tribe Tegonotini (Eriophyidae: Phyllocoptinae) from North Bengal, India. Aciota secundum Flechtmann et al.1995 is re-assigned (n. comb.) to Propeaciota. Relationships of the new genera with other eriophyoid genera are discussed.


Risk-reducing strategies for repair of complex ascending aortic false aneurysms.
Late presentation of aortic false aneurysm following repair of acute type A aortic dissection occurs in 10% to 24% of cases. This condition is associated with high mortality if left untreated. Herein we describe a combination of surgical strategies that we believe may be used effectively to reduce the surgical risk of these complex operations.


Spreading depression triggers headache by activating neuronal Panx1 channels.
The initial phase in the development of a migraine is still poorly understood. Here, we describe a previously unknown signaling pathway between stressed neurons and trigeminal afferents during cortical spreading depression (CSD), the putative cause of migraine aura and headache. CSD caused neuronal Pannexin1 (Panx1) megachannel opening and caspase-1 activation followed by high-mobility group box 1 (HMGB1) release from neurons and nuclear factor κB activation in astrocytes. Suppression of this cascade abolished CSD-induced trigeminovascular activation, dural mast cell degranulation, and headache. CSD-induced neuronal megachannel opening may promote sustained activation of trigeminal afferents via parenchymal inflammatory cascades reaching glia limitans. This pathway may function to alarm an organism with headache when neurons are stressed.


[Adsorption of plasma proteins on the surface of hydrophobic polymers. Structural aspects].
The qualitative and quantitative composition of the adsorbed protein layer is determined by thromboresistance of artificial polymer surface. The adsorption of albumine and gammaglobuline from buffer solution to the hydrofobic polymer surfaces was investigated with ESR and electron spectroscopic method. The existence of two kinds of protein covering was demonstrated: reversible and irreversible protein layer. During the nitroxyl labelled globuline adsorption the spectrum of label is due to superposition of both reversible and irreversible kinds of adsorption. It was demonstrated by the electron microscopic method that the strongly adsorbed protein layer corresponds with the denaturated protein, the reversibly adsorbed protein in contrast is native. The architecture of protein layer on polymer surface was also investigated. The comparison of structural and physiological properties of serum protein is important for the investigation of the thromboresistant materials.


Abnormal dendritic spines in fragile X knockout mice: maturation and pruning deficits.
Fragile X syndrome arises from blocked expression of the fragile X mental retardation protein (FMRP). Golgi-impregnated mature cerebral cortex from fragile X patients exhibits long, thin, tortuous postsynaptic spines resembling spines observed during normal early neocortical development. Here we describe dendritic spines in Golgi-impregnated cerebral cortex of transgenic fragile X gene (Fmr1) knockout mice that lack expression of the protein. Dendritic spines on apical dendrites of layer V pyramidal cells in occipital cortex of fragile X knockout mice were longer than those in wild-type mice and were often thin and tortuous, paralleling the human syndrome and suggesting that FMRP expression is required for normal spine morphological development. Moreover, spine density along the apical dendrite was greater in the knockout mice, which may reflect impaired developmental organizational processes of synapse stabilization and elimination or pruning.


smAMPsTK: a toolkit to unravel the smORFome encoding AMPs of plant species.
The pervasive repertoire of plant molecules with the potential to serve as a substitute for conventional antibiotics has led to obtaining better insights into plant-derived antimicrobial peptides (AMPs). The massive distribution of Small Open Reading Frames (smORFs) throughout eukaryotic genomes with proven extensive biological functions reflects their practicality as antimicrobials. Here, we have developed a pipeline named smAMPsTK to unveil the underlying hidden smORFs encoding AMPs for plant species. By applying this pipeline, we have elicited AMPs of various functional activity of lengths ranging from 5 to 100 aa by employing publicly available transcriptome data of five different angiosperms. Later, we studied the coding potential of AMPs-smORFs, the inclusion of diverse translation initiation start codons, and amino acid frequency. Codon usage study signifies no such codon usage biases for smORFs encoding AMPs. Majorly three start codons are prominent in generating AMPs. The evolutionary and conservational study proclaimed the widespread distribution of AMPs encoding genes throughout the plant kingdom. Domain analysis revealed that nearly all AMPs have chitin-binding ability, establishing their role as antifungal agents. The current study includes a developed methodology to characterize smORFs encoding AMPs, and their implications as antimicrobial, antibacterial, antifungal, or antiviral provided by SVM score and prediction status calculated by machine learning-based prediction models. The pipeline, complete package, and the results derived for five angiosperms are freely available at https://github.com/skbinfo/smAMPsTK.Communicated by Ramaswamy H. Sarma.


Differential effects of dehydroepiandrosterone and deoxyribonucleosides on DNA synthesis and de novo cholesterogenesis in hepatocarcinogenesis in rats.
Previous studies from our laboratory have shown that dehydroepiandrosterone (DHEA), an inhibitor of glucose-6-phosphate dehydrogenase (G6PD), prevents the development of gamma-glutamyltranspeptidase (GGT)-positive foci in the early stages of hepatocarcinogenesis in rats. Since high rates of DNA and cholesterol (CH) synthesis are observed during promotion of carcinogenesis, and mevalonate (MVA), or some other intermediates of CH synthesis, could be mediators of DNA synthesis, we investigated the effect of DHEA on CH synthesis in rat liver during the development of GGT-positive foci. Hepatocarcinogenesis was induced by diethylnitrosamine in female Wistar rats by the Solt-Farber protocol (initiation/selection) with and without phenobarbital treatment. A 15 day treatment with DHEA (0.6% in the diet), started after selection, caused a great fall in labeling and mitotic indices of GGT-positive foci, which was prevented by the simultaneous administration of a mixture of four deoxyribonucleosides (DRNs) of adenine, guanine, cytosine and thymine or four ribonucleosides (RNs) of adenine, guanine, cytosine and uridine, but not by the corresponding bases. DHEA greatly inhibited G6PD activity and the production of ribulose-5-phosphate, without affecting NADPH levels, due to the compensatory increase in malic enzyme and isocitric dehydrogenase activities. Serum lecithin/cholesterol acyltransferase activity underwent a reduction in conditions allowing a rapid growth of GGT-positive tissue (absence of DHEA or presence of DHEA plus DRNs or RNs). Liver slices isolated from DHEA-treated rats showed a rise in CH content, coupled with a 80% fall in the incorporation of labeled acetate, but not of labeled MVA, into CH. A 25 day treatment of rats subjected to initiation/selection, started after the appearance of persistent nodules, caused a 36 and 78% fall in the incorporation, in vivo, of 3H2O into nodular and surrounding liver CH respectively. DRN did not counteract DHEA-induced inhibition on CH synthesis. Thus DHEA inhibits the CH biosynthetic pathway before MVA synthesis, in conditions (presence of DHEA plus DRN/RN) allowing rapid growth of preneoplastic lesions. Therefore, the development of these lesions does not need the synthesis of large amounts of CH and CH metabolites. Thus, the antipromotion effect of DHEA may depend on a decreased availability of pentose phosphates for DNA synthesis.


[Treatment strategy of lateral canals during root canal therapy].
Lateral canals are small branches from the main root canal, usually extending from the dentin and cementum into the periodontal ligament, mostly located at the lower 1/3 of the apical portion. Due to the complex and varied anatomical morphology as well as the high incidence, it becomes an important factor affecting the effect of root canal therapy and a difficult point in this process. It is of great clinical significance to master the treatment strategy of lateral canals during root canal therapy. This article reviews the anatomical characteristics of lateral canals, as well as the clinical identification, treatment strategy and the laboratory detection methods of lateral canals in the process of root canal preparation, disinfection, and obturation.


Research into the Value of B-Mode Ultrasound, CT and MRI Examinations in the Diagnosis of Preoperative Myometrial Infiltration of Endometrial Cancer and Lymph Node Metastasis.
This study is conducted to observe the diagnostic value of B-mode ultrasound, CT and MRI examinations in preoperative myometrial infiltration of endometrial cancer and lymph node metastasis. Retrospectively analyze 50 cases of the patients from Oct. 2010 to Aug. 2013. Before operation all the patients received dilatation & curettage to determine pathological diagnosis and clinical staging. There were 150 cases of patients who received B-mode ultrasound examination, wherein, 93 cases received CT examination and 57 cases received MRI examination as well. In the diagnosis of MIEC the diagnostic indicies of individual MRI examination were higher than that of individual B-mode ultrasound and CT examinations. Consistency of individual MRI examination with pathological diagnosis was significantly higher than that of B-mode and CT examinations. The sensitivity of CT and MRI was significantly higher than that of B-mode ultrasound examination. However, diagnostic indicators of B-mode ultrasound and CT joint examination were higher than B-mode ultrasound examination alone. The consistency of both with pathological diagnosis was significantly increased. B-mode and CT can significantly improve the diagnostic accuracy and has a good consistency with pathological diagnosis, thereby applicable to the clinical diagnosis of preoperative myometrial infiltration of endometrial cancer and lymph node metastasis.


Kinetics and mechanism of the comproportionation of hypothiocyanous acid and thiocyanate to give thiocyanogen in acidic aqueous solution.
The kinetics of comproportionation of hypothiocyanous acid (HOSCN) and thiocyanate (SCN-) to give thiocyanogen ((SCN)2) in acidic aqueous solutions have been determined by double-mixing stopped-flow UV spectroscopy. Hypothiocyanite (OSCN-) was generated at pH 13 by oxidation of excess SCN- with hypobromite (OBr-), followed by a pH jump to acidic conditions ([H+] = 0.20-0.46 M). The observed pseudo-first-order rate constants exhibit first-order dependencies on [H+] and [SCN-] with overall third-order kinetics. The corresponding kinetics of hydrolysis of (SCN)2 have also been examined. Under conditions of high (and constant) [H+] and [SCN-], the kinetics exhibit second-order behavior with respect to [(SCN)2] and complex inverse dependences on [H+] and [SCN-]. Under conditions of low [H+] and [SCN-], the kinetics exhibit first-order behavior with respect to [(SCN)2] and independence with respect to [H+] and [SCN-]. We attribute this behavior to a shift in the rate-limiting step from disproportionation of HOSCN (second-order dependency on [(SCN)2]) to rate-limiting hydrolysis (first-order dependency on [(SCN)2]). Thus, we have determined the following equilibrium constant by the kinetic method: (SCN)2 + H2O HOSCN + SCN- + H+; Khyd = [HOSCN][SCN-][H+]/[(SCN)2] = khyd/kcomp = 19.8(+/-0.7) s-1/ 5.14(+/-0.07) x 103 M-2 s-1 = 3.9 x 10-3 M2.


Diagnostic validation and prognostic significance of the Malnutrition-Inflammation Score in nondialyzed chronic kidney disease patients.
Malnutrition and inflammation are highly prevalent and intimately linked conditions in chronic kidney disease (CKD) patients that lead to a state of protein-energy wasting (PEW), the severity of which can be assessed by the Malnutrition-Inflammation Score (MIS). Here, we applied MIS and validated, for the first time, its ability to grade PEW and predict mortality in nondialyzed CKD patients. We cross-sectionally evaluated 300 CKD stages 3-5 patients [median age 61 (53-68) years; estimated glomerular filtration rate 18 (12-27) mL/min/1.73 m(2); 63% men] referred for the first time to our center. Patients were followed during a median 30 (18-37) months for all-cause mortality. A worsening in MIS scale was associated with inflammatory biomarkers increase (i.e. alpha-1 acid glycoprotein, fibrinogen, ferritin and C-reactive protein) as well as a progressive deterioration in various MIS-independent indicators of nutritional status based on anthropometrics, dynamometry, urea kinetics and bioelectric impedance analysis. A structural equation model with two latent variables (assessing simultaneously malnutrition and inflammation factors) demonstrated good fit to the observed data. During a follow-up, 71 deaths were recorded; patients with higher MIS were at increased mortality risk in both crude and adjusted Cox models. MIS appears to be a useful tool to assess PEW in nondialyzed CKD patients. In addition, MIS identified patients at increased mortality risk.


Innovation, Translation, and Cooperation.
The 9th Wound Healing and Tissue Repair and Regeneration Annual Meeting of Chinese Tissue Repair Society was hold in Wuhan, China. This meeting was focused on the innovation, translation application, and cooperation in wound care both in China and other countries. More than 400 delegates took part in this meeting and communicated successfully.


Honduranura centraliamericana gen. n. et sp. n. from Central America (Collembola, Neanuridae, Neanurinae).
Honduranuragen. n. and the type species H. centraliamericanasp. n. are described and illustrated. The new genus shows the characters of Sensillanurini Cassagnau, 1983 tribe and is distinguished by the fusion of cephalic and abdominal tubercles: clypeal with antennofrontal and dorsointernal with dorsoexternal on head; presence of fused tubercles on each side of abdominal segment V. Most of the tubercles bear strong subcuticular reticulation. A key for the genera of the tribe Sensillanurini is provided.


A quantitative proteomics-based signature of platinum sensitivity in ovarian cancer cell lines.
Although DNA encodes the molecular instructions that underlie the control of cell function, it is the proteins that are primarily responsible for implementing those instructions. Therefore quantitative analyses of the proteome would be expected to yield insights into important candidates for the detection and treatment of disease. We present an iTRAQ (isobaric tag for relative and absolute quantification)-based proteomic analysis of ten ovarian cancer cell lines and two normal ovarian surface epithelial cell lines. We profiled the abundance of 2659 cellular proteins of which 1273 were common to all 12 cell lines. Of the 1273, 75 proteins exhibited elevated expression and 164 proteins had diminished expression in the cancerous cells compared with the normal cell lines. The iTRAQ expression profiles allowed us to segregate cell lines based upon sensitivity and resistance to carboplatin. Importantly, we observed no substantial correlation between protein abundance and RNA expression or epigenetic DNA methylation data. Furthermore, we could not discriminate between sensitivity and resistance to carboplatin on the basis of RNA expression and DNA methylation data alone. The present study illustrates the importance of proteomics-based discovery for defining the basis for the carboplatin response in ovarian cancer and highlights candidate proteins, particularly involved in cellular redox regulation, homologous recombination and DNA damage repair, which otherwise could not have been predicted from whole genome and expression data sources alone.


Assessment of sodium benzoate and potassium sorbate preservatives in some products in Kashan, Iran with estimation of human health risk.
The purpose was to assess of sodium benzoate (SB) and potassium sorbate (PS) preservatives in 103 samples of cake, toast bread, tomato paste, mayonnaise sauce, carbonated soft drink and Olovieh salad in Kashan, by spectrophotometry and high performance liquid chromatography (HPLC) methods. The chronic daily intake (CDI), target hazard quotient (THQ) and hazard index (HI) of SB and PS for Iranian population were calculated. The results showed that SB and PS were not detected in the tomato paste samples. SB and PS concentrations for all samples were less than regulatory limits except for PS in one cake sample (3.57%). CDI and THQ of PS for mayonnaise sauce, Olovieh salad and cake products, except toast bread, were less than the acceptable daily intakes (ADIs) and one, respectively. While HI value of PS for the selected products was more than one, indicating that the non-carcinogenic risk represent a threat to consumers. THQ and HI values of SB for mayonnaise sauce and carbonated soft drink products were more than one through consumption of these products, indicating considerable non-carcinogenic risk. Therefore, the results highlighted the importance of a more attentive monitoring of these preservatives by the public and food health authorities in Iran.


Late-Onset Cognitive Impairments after Early-Life Stress Are Shaped by Inherited Differences in Stress Reactivity.
Early-life stress (ELS) has been associated with lasting cognitive impairments and with an increased risk for affective disorders. A dysregulation of the hypothalamus-pituitary-adrenal (HPA) axis, the body's main stress response system, is critically involved in mediating these long-term consequences of adverse early-life experience. It remains unclear to what extent an inherited predisposition for HPA axis sensitivity or resilience influences the relationship between ELS and cognitive impairments, and which neuroendocrine and molecular mechanisms may be involved. To investigate this, we exposed animals of the stress reactivity mouse model, consisting of three independent lines selectively bred for high (HR), intermediate (IR), or low (LR) HPA axis reactivity to a stressor, to ELS and assessed their cognitive performance, neuroendocrine function and hippocampal gene expression in early and in late adulthood. Our results show that HR animals that were exposed to ELS exhibited an HPA axis hyper-reactivity in early and late adulthood, associated with cognitive impairments in hippocampus-dependent tasks, as well as molecular changes in transcript levels involved in the regulation of HPA axis activity (Crh) and in neurotrophic action (Bdnf). In contrast, LR animals showed intact cognitive function across adulthood, with no change in stress reactivity. Intriguingly, LR animals that were exposed to ELS even showed significant signs of enhanced cognitive performance in late adulthood, which may be related to late-onset changes observed in the expression of Crh and Crhr1 in the dorsal hippocampus of these animals. Collectively, our findings demonstrate that the lasting consequences of ELS at the level of cognition differ as a function of inherited predispositions and suggest that an innate tendency for low stress reactivity may be protective against late-onset cognitive impairments after ELS.


Use of a complete autologous blood recovery system (the Sorin Xtra® Autotransfusion System) during mechanical thrombectomy of extensive cerebral venous sinus thrombosis.
Background The endovascular therapy for cerebral venous sinus thrombosis (CVST) is currently accepted as a second-line treatment for patients who have failed or those in whom systemic anticoagulation is contraindicated or in a subgroup of patients presenting with rapid neurologic deterioration. A number of different mechanical and pharmacologic endovascular strategies have been reported, either as separate or combined approaches. These new catheters and aspiration systems have a high power and vacuum capacity, which carries a risk of anemization of the patient and hypovolemic shock, being necessitating the transfusion of the patient. Material and methods Because of the problems that donor blood transfusion can bring, we describe the use of a Sorin Xtra® Autotransfusion System (ATS). This complete autologous blood recovery system was designed for use in procedures where medium- to high-volume blood loss occurs, such as major surgeries. We have adapted it to recover all the blood aspirated during the mechanical thrombectomy procedures of the dural cerebral venous sinuses, since they are procedures that can cause a significant loss of blood. One advantage to this is the patient receives his or her own blood instead of donor blood, so there is no risk of contracting outside diseases or transfusion reactions. Conclusions This technical note describes a novel and previously unpublished technical approach to CVST that can be immediately applied to clinical practice. It also raises awareness among the interventional neuroradiologist and anesthesiologist communities about novel, potentially lifesaving endovascular treatments in patients with extensive CVST.


From a master to a laywoman: a feminine manual of self-help.
This article analyzes master Joan's Trotula, a late fourteenth-century Catalan text on women's health addressed to an infanta of Aragon which survives in one late fourteenth-century manuscript. It presents a hypothesis regarding its genre, its composition and use at the Catalan-Aragonese Court, and its later fortuna. It considers how Master Joan inscribed in the text a conception of women's medical needs, while also defining lay women's involvement in maintaining their health.


The Child Attachment Interview: A Narrative Review.
Attachment theory promoted an impressive body of research on the psychic developmental processes, resulting in studies on both typical and atypical development. Much of the diffusion of the attachment theory in the clinical field was related to the design of reliable instruments to evaluate the organization of attachment in infancy as well as in adulthood. Until recently, the lack of a suitable instrument to assess attachment in middle childhood as well as in adolescence hindered the expansion of research in these developmental phases during which the parent-child relationship takes on a different, albeit still crucial, role. The Child Attachment Interview (CAI), a measure that was recently designed to assess attachment at a representational level in middle childhood and adolescence, filled the measurement gap. The aim of the current review was to summarize previous empirical investigations concerning CAI in order to (a) provide an overview of the state of current research, (b) identify unanswered questions, and (c) propose future research directions. A narrative review was conducted to map the current research findings by searching for the term "Child Attachment Interview" in the Medline, Scopus, Web of Science, and PsychINFO databases, followed by a search in Mendeley. Limits were set to exclude dissertations, chapters in books, and qualitative or theoretical papers, while empirical studies were included if they used the CAI and were published in English language, peer-reviewed journals by July, 2016. The review, which ultimately included 39 studies meeting the criteria, showed that the CAI is a reliable instrument to assess attachment organization in clinical and non-clinical samples, thus providing a worthwhile contribution to the investigation of the influence of the parent-child relationship beyond infancy and early childhood. Nevertheless, the review pointed out a number of relevant open issues, the most critical of which concerned the CAI coding and classification system. In particular, some relevant questions arose about (a) how opportune it would be to maintain a distinct classification for mother and father, (b) coding challenges regarding both the father and the Preoccupied and Disorganized classification, and finally (c) the advantage of a dimensional vs. a categorical approach.


Insulin and release of neurohypophysial hormones: in vivo and in vitro studies.
No significant effect of intracerebroventricular administration of insulin on the bioassayed neurohypophysial storage of vasopressin and oxytocin could be found. This finding, however, only indirectly reflects possible changes of vasopressin and oxytocin release. Incubation of neurointermediate lobes in Locke's solution containing 3.3 mumol/l insulin resulted in an inhibition of oxytocin release under resting conditions as well as in a decrease of both vasopressin and oxytocin release during depolarization due to excess potassium. These results seem to suggest a possible regulatory role of brain insulin in the mechanisms of release of neurohypophysial hormones.


A study of the ultrastructure of the buffalo pox virus.
Buffalo pox virus (strain BP 4) has been studied by electron microscopy of sections of infected chorioallantoic membrane cells. The ultrastructure of the virus has been described and compared with the ultrastructure of vaccinia virus. No differences between the two viruses were found. In relation to the ways of release two forms of mature virions have been described. These are probably analogous to the previously described C- and M-form of vaccinia.


Detection of plasmid-mediated AmpC β-lactamase in Escherichia coli.
Escherichia coli (E. coli) is a common opportunistic pathogen for nosocomial infection. The aim of the study was to examine the phenotype, genotype and epidemiology of plasmid-mediated AmpC β-lactamases in E. coli. In total, 96 clinical isolates of repeated E. coli were collected from different hospitals between August and October 2012. Using a cefoxitin disk diffusion method to identify the phenotype of AmpC β-lactamases in E. coli, the plasmid was extracted, and multiplex polymerase chain reaction (PCR) was used to determine the amp gene. The PCR products were purified and sequenced. Of the 96 isolates strains, 43 strains were cefoxitin-resistant. Twelve (12.5%) isolates were detected to produce AmpC β-lactamases with multiplex PCR, 11 strains carried DHA type ampC-resistant genes, and one strain carried ACC type ampC-resistant genes. In conclusion, the incidence of producing a plasmid-mediated AmpC enzyme of E. coli strains was relatively high. Therefore, antibiotics such as imipenem, a carbapenem, potentially serve as the treatment of choice for the infection.


Daylong pituitary hormones in morbid obesity: effects of bariatric surgery.
Moderate obesity is known to be associated with multiple endocrine abnormalities. Less information is available on the hormonal status of patients with morbid obesity and on the effects of major weight loss. We studied 16 severely obese (BMI 40.6-69.9 kg/m(2)) nondiabetic patients and 7 nonobese (BMI range 24.6-27.7 kg/m(2)), sex- and age-matched healthy volunteers. During 24 h in a metabolic ward, four meals were administered and hourly blood samples were drawn from a central venous catheter for the measurement of glucose, insulin, leptin, thyrotropic hormone (TSH), growth hormone (GH) and prolactin. Insulin sensitivity was measured by a euglycaemic hyperinsulinaemic clamp. Studies were repeated 6 months after biliopancreatic diversion, a mainly malabsorptive surgical approach, which caused an average weight loss of 35+/-4 kg (or 26+/-2% of initial weight). Compared with controls, patients were hyperinsulinaemic (290+/-31 vs 88+/-4 pmol l(-1), P=0.0002), insulin resistant (23.5+/-2.8 vs 52.9+/-4.9 micromol min(-1) kg(FFM)(-1), P=0.0006) and hyperleptinaemic (52.5+/-5.8 vs 10.9+/-3 ng ml(-1), P=0.0002). Plasma TSH levels were increased throughout the day-night cycle (averaging 2.02+/-0.18 vs 1.09+/-0.19 muU ml(-1) of controls, P=0.01), whereas serum GH levels were suppressed (0.46+/-0.10 vs 3.01+/-1.15, P=0.002). Following surgery, the hyperinsulinaemia and insulin resistance were fully normalized; in concomitance with a major drop in leptin levels (to 14.4+/-2.7 ng ml(-1), P=0.02), TSH decreased and GH increased to near-normal levels. In the whole dataset, mean 24-h leptin levels were directly related to mean 24-h TSH levels after controlling for confounders this relationship was lost only after adjusting for fat mass. We conclude that in morbid obesity leptin is a determinant of changes in pituitary function.


Contexts motivating protective behaviours related to Aedes-borne infectious diseases in Curaçao.
Aedes aegypti, the vector of arboviral diseases such as dengue and Zika virus infections, is difficult to control. Effective interventions must be practicable, comprehensive, and sustained. There is evidence that community participation can enhance mosquito control. Therefore, countries are encouraged to develop and integrate community-based approaches to mosquito control to mitigate Aedes-borne infectious diseases (ABIDs). Health professionals must understand the contexts motivating individuals' behaviour to improve community participation and promote behavioural change. Therefore, this study aimed to determine how contexts shaped individuals' protective behaviours related to ABIDs in Curaçao. From April 2019 to September 2020, a multi-method qualitative study applying seven (n = 54) focus group discussions and twenty-five in-depth interviews with locals was performed in Curaҫao. The study was designed based on the Health Belief Model (HBM). Two cycles of inductive and deductive coding were employed, and Nvivo software was used to manage and analyse the data. In this study, low media coverage (external cue to action) and limited experience with the symptoms of ABIDs (internal cue to action) were linked with a low perceived susceptibility and severity of ABIDs (low perceived threat). The low perceived threat was linked with reduced health-seeking behaviour (HSB) to prevent and control ABIDs. We also found that the perceived barriers outweigh the perceived benefits of ABID prevention and control interventions, obstructing HSB. On the one hand, insufficient knowledge reduced self-efficacy but contrary to expected, having good knowledge did not promote HSB. Lastly, we found that our participants believe that they are responsible for preventing ABIDs (internal locus of control) but at the same time indicated that their success depends on the efforts of the community and the health system (external locus of control). This study used the HBM to explain individual changes in HSB concerning ABIDs prevention and control in Curaçao. We can conclude that the perceived threat (perceived susceptibility and severity) and perceived barriers played an essential role in changing HSB. Health professionals must consider these two concepts' implications when designing a bottom-up approach for ABIDs control; otherwise, community participation will remain minimal.


Shape-controlled synthesis of triangular gold nanoprisms using microwave irradiation.
In this report, we described the very fast synthesis of gold nanoprisms under microwave heating for 60-90 s in the presence of 2-naphthol (2-N) as a new reducing agent. The growth of the particles with different shapes (spherical, polygonal or triangular/prisms etc.) were found to be functions of the surfactant-to-metal-ion molar ratio and the concentration of 2-N. The evolved nanoprisms were approximately 110 +/- 10 nm in diameter and the particles size and shape was successfully tuned just by varying the molar ratio of the reactants. This process can be extended to the synthesis of other nonmaterial with desired sizes and shapes. The method we generated might find variety of application in many areas such as catalysis, clinical and diagnostic medicine, and nanoelectronics.


[The post-cholecystectomy syndrome. Evaluation of symptomatology using Tc-99m-HIDA sequential hepatic scintigraphy (cholescintigraphy)].
The authors comment the data from research on 70 patients with post cholecystectomy syndrome, using cholescintigraphy HIDA 99mTc to evaluate the relation ship between symptomatology (see classific.) and duodenogastric reflux entity. Cholescintigraphy seems to be a valid clinical means, especially for a correct indication to endoscopy.


Identification of a New Antimicrobial Agent against Bovine Mastitis-Causing Staphylococcus aureus.
Staphylococcus aureus RF122 is a major pathogen that causes bovine mastitis, which is the most prevalent and costly disease in the milk and dairy industry. S. aureus expresses various virulence factors that are especially highly associated with iron metabolism, and the bacterial ferrous iron transport system Feo is important for bacterial growth or virulence in mammalian hosts. In this study, we evaluated a new antimicrobial agent, PHT-427, targeting the S. aureus RF122 Feo system for the prevention of bovine mastitis. Various analyses on in vitro enzymatic assays, growth inhibition, virulence expressions, and toxicity of animal model systems were conducted to characterize the inhibition properties of PHT-427. This small molecule efficiently inhibited enzyme activity of FeoB and bacterial growth. PHT-427 attenuated various virulence factors related to milk quality, including staphyloxanthin production, biofilm formation, and coagulation. Considering the high frequency of antibiotic-resistant S. aureus in bovine mastitis isolates, PHT-427 synergistically enhanced bacterial antibiotic susceptibility and further inhibited global Gram-positive bacterial growth. Unlike its effects on bacteria, the inhibitor did not show any toxicity on animal model systems. These results indicate that the S. aureus Feo system represents a good target for antimicrobial strategies, and this new antimicrobial agent may represent a promising biotechnological application for preventing S. aureus-induced bovine mastitis in the milk and dairy industry.


A web of intrigue: the search for quality in qualitative research.
This paper reports an investigation about 'quality' in qualitative research. For educatorsand students of nursing and midwifery, it serves as an exemplar for tackling vexing research questions, and as a model for creative research reporting. Practising qualitative researchers (post-doctoral nurses and midwives) from different countries were asked to identify the characteristics of what they considered to be a high quality published report of qualitative research. They then commented upon one another's characteristics with a view to comparing and compiling ideas. Four themes were identified from the data, relatingto process, writing, outcome and excellence. The study highlights shifts in thinking about determinants of quality in qualitative research over time, and current challenges for researchers, consumers and others in the face of declining interest in quality criteria.A spider's web is used as a met aphor for the study to illustrate the enmeshment and intrigue that the research and its findings generated for the researchers, participantsand onlookers.


[Current and future medical treatment of Alzheimer's disease].
The current treatment of Alzheimer's disease (MA) is based on a symptomatic pharmacological therapy of the cognitive decline and the behavioural disturbances. Progress towards understanding the cellular and molecular alterations responsible for the disease promise therapeutic strategies based upon the pathological processes. Corrections of dysregulations of the brain's neurotransmitters (cholinergic deficit and glutamatergic overstimulation) bring significant but modest therapeutic improvement. The pivotal role of the proteolytic processing of the amyloid precursor protein (APP) in neuronal death suggests pharmacological inhibition of the secretases; amyloid antiaggregant therapies are possible, vaccination against AB wil need new immunisation protocols, Anti-inflammatory drugs and antioxydant agents as calcium channel blockers could help against the neurotoxic cascade of Abeta, some cholesterol-lowering drugs could enhance its clearance. This article reviews the available data on current pharmacological treatments, and the future possible strategies that could modify the evolution, or prevent Alzheimer's disease.


An integrated LC-ESI-MS platform for quantitation of serum peptide ladders. Application for colon carcinoma study.
Mounting evidence indicates that MS analysis of the human blood peptidome allows to distinguish between cancer and non-cancer samples, giving promise for a new MS-based diagnostic tool. However, several aspects of already published work have been criticized and demand for more methodical approach has been formulated. Motivated by this we undertook a systematic study of the plasma and serum peptidome using an integrated ESI-LC-MS-based platform, equipped with new data analysis tools for relative and absolute peptide quantitation. We used a high resolution LC-ESI-MS to analyze well-separated MS signals corresponding to peptides, and measured the variability of >1000 peptide signal amplitudes across a set of plasma and serum samples from healthy individuals. By spiking serum samples with known amounts of isotopically labeled versions of a selected set of peptides we measured the variability of their absolute concentration in this sample set and demonstrated a strong influence of clotting time on the concentration of these peptides in serum. Finally, we used this new LC-ESI-MS analytical platform for the differential analysis of healthy versus colon cancer serum samples and found that it was possible to distinguish the two groups with 89.8% sensitivity and 94.6% specificity.


Primary intestinal and thoracic lymphangiectasia: a response to antiplasmin therapy.
Lymphangiectasia is a congenital or acquired disorder characterized by abnormal, dilated lymphatics with a variable age of presentation. We describe a case of lymphangiectasia with intestinal and pulmonary involvement in an adolescent female, who presented with many of the classic features including chylous pleural effusions, lymphopenia, hypogammaglobinemia, and a protein-losing enteropathy. She also presented with recurrent lower gastrointestinal bleeding, which is infrequently described. The patient did not improve with bowel rest and a low-fat medium-chain triglyceride diet and had little improvement with octreotide acetate therapy. However, she had a clinical response to antiplasmin therapy, trans-4-aminothylcyclohexamine carboxylic acid (tranexamic acid) in terms of serum albumin and gastrointestinal bleeding. She continues to have exacerbations of her condition, as well as persistent lymphopenia and chronic pleural effusions.


Histone Deacetylase-1-mediated Suppression of FAS in Chemoresistant Ovarian Cancer Cells.
Loss of FAS expression in ovarian cancer cells has recently been associated with resistance to chemotherapeutic drugs. However, the mechanism for suppression of FAS expression is unknown. The cell surface and transcript expressions of death receptors in parental chemosensitive (A2780) and their derivative chemoresistant (A2780-AD) ovarian cancer cells were determined by flow cytometry and quantitative real-time polymerase chain reaction, respectively. The epigenetic regulation of FAS promoters in both A2780 and A2780-AD ovarian epithelial cells were determined by chromatin immunoprecipitation assays. This study demonstrated that expression of FAS is suppressed in A2780-AD cells compared to parental A2780 ovarian cells. No difference in DNA methylation was observed at FAS promoters between A2780-AD cells compared to parental cells. However, the level of acetylated histone H3 associated with FAS promoter in A2780-AD cells was significantly lower compared to parental cells, and there was a corresponding increase in histone deacetylase 1 (HDAC1) enzyme associated with the FAS promoter in resistant cells. Knockdown of HDAC1 expression, and pharmacological inhibition of HDAC enzymatic activity significantly increased FAS expression in resistant A2780-AD cells. These results suggest that epigenetic changes in histone modifications may contribute to the loss of FAS expression in chemoresistant ovarian cancer cells and that enhancement of FAS expression could increase tumor cell sensitivity to immune cells.


Matrix metalloproteinases in autism spectrum disorders.
Autism Spectrum Disorders (ASD) are group of developmental disabilities with a complex neurobiological basis including putative changes in the immune system. They are characterized by pervasive qualitative abnormalities in social interactions, communication, and stereotyped behaviour. Matrix metalloproteinases (MMPs) represent a group of proteases which play an important role in neuroinflammation and neurodevelopment. Therefore, they possibly have a crucial function in the etiopathology of ASD. In this review, we summarize the plausibility of the hypothesis that MMPs are involved in the neuropathology of ASD. Possible pathways through which MMPs can contribute to the pathogenesis of ASD are discussed including neuroinflammatory mechanisms inclusive of mediating neuropathological effects of infections, the associations between MMPs and other biomarkers such as cytokines, chemokines and neurotrophic factors. Despite sufficient evidence for such an involvement of MMPs in the neuropathology of ASD, they have not yet been extensively studied in this context. Thus, further research in this field is not only urgently needed but also very promising and may also lead to new therapeutic approaches.


Assessment of physical activity, energy expenditure and energy intakes of young men practicing aerobic sports.
Adequate nutrition and energy intake play key rule during the training period and recovery time. The assessment of athlete's energetic needs should be calculated individually, based on personal energy expenditure and Sense Wear PRO3 Armband (SWA) mobile monitor is a useful tool to achieve this goal. However, there is still few studies conducted with use of this monitor. To assess individual energy needs of athletes by use of SWA and to determine whether their energy intake fulfils the body's energy expenditure. Subjects were 15 male students attending Military University of Technology in Warsaw, aged 19-24 years, practicing aerobic. The average body mass was 80.7 ± 7.7 kg and average height was 186.9 ± 5.2 cm, (BMI 23.09 ± 1.85 kg/m2). Assessment of physical activity and energy expenditure (TEE) was established using SWA, which was placed on the back side of dominant hand and worn continuously for 48 hours (during the training and non-training day). The presented results are the average values of these 2 days. Assessment of athletes' physical activity level was established by use of metabolic equivalent of task (MET) and number of steps (NS). Estimation of energy intake was based on three-day dietary recalls (two weekdays and one day of the weekend), evaluated using the Polish Software 'Energia' package. The average TEE of examined athletes was 3877 ± 508 kcal/day and almost half of this energy was spend on physical activity (1898 ± 634 kcal/day). The number of steps was on average 19498 ± 5407 and average MET was 2.05 ± 2.09. The average daily energy intake was 2727 ± 576 kcal. Athletes consumed inadequate amount of energy in comparison to their energy expenditure. Examined group did not have an adequate knowledge about their energy requirement, which shows the need of nutritional consulting and education among these athletes. athletes, aerobic sports, energy expenditure, energy intake.


[Allergenicity of oils].
Cases of allergy to the oils of groundnut, sunflower, soya and sesame have been described in the literature. In parallel, other authors have affirmed that these oils are not allergenic. The objective of this article is to make the point on this question, to cite the procedures to which the seeds are submitted to extract the oil, to remember that the oils are not composed only of triglycerides and to describe the results of our work. Allergy of oils is a subject that is constantly submitted to controversy and the bibliography does not cease to give contradictory examples. This may be explained by the variations in extraction procedures used by the manufactures, as well as by the conditions of extraction of the proteins in the laboratory.


Activity-Dependent Modulation of Tonic GABA Currents by Endocannabinoids in Hirudo verbana.
Endocannabinoids are lipid neuromodulators that are synthesized on demand and primarily signal in a retrograde manner to elicit depression of excitatory and inhibitory synapses. Despite the considerable interest in their potential analgesic effects, there is evidence that endocannabinoids can have both pro-nociceptive and anti-nociceptive effects. The mechanisms contributing to the opposing effects of endocannabinoids in nociception need to be better understood before cannabinoid-based therapies can be effectively utilized to treat pain. Using the medicinal leech, Hirudo verbana, this work investigates whether endocannabinoids modulate tonic inhibition onto non-nociceptive afferents. In voltage clamp recordings, we analyzed changes in the tonic inhibition in pressure-sensitive (P) cells following pre-treatment with endocannabinoids, 2-arachidonoylglycerol (2-AG) or anandamide (AEA). We also tested whether high frequency stimulation (HFS) of nociceptive (N) cells could also modulate tonic inhibition. Both endocannabinoid application and N cell HFS depressed tonic inhibition in the P cell. Depression of tonic inhibition by N cell HFS was blocked by SB 366791 (a TRPV1 inhibitor). SB 366791 also prevented 2-AG-and AEA-induced depression of tonic inhibition. HFS-induced depression was not blocked by tetrahydrolipstatin (THL), which prevents 2-AG synthesis, nor AM 251 (a CB1 receptor inverse agonist). These results illustrate a novel activity-dependent modulation of tonic GABA currents that is mediated by endocannabinoid signaling and is likely to play an important role in sensitization of non-nociceptive afferent pathways.


Haphazard reporting of deaths in clinical trials: a review of cases of ClinicalTrials.gov records and matched publications-a cross-sectional study.
A participant death is a serious event in a clinical trial and needs to be unambiguously and publicly reported. To examine (1) how often and how numbers of deaths are reported in ClinicalTrials.gov records; (2) how often total deaths can be determined per arm within a ClinicalTrials.gov results record and its corresponding publication and (3) whether counts may be discordant. Registry-based study of clinical trial results reporting. ClinicalTrials.gov results database searched in July 2011 and matched PubMed publications. A random sample of ClinicalTrials.gov results records. Detailed review of records with a single corresponding publication. ClinicalTrials.gov records reporting number of deaths under participant flow, primary or secondary outcome or serious adverse events. Consistency in reporting of number of deaths between ClinicalTrials.gov records and corresponding publications. In 500 randomly selected ClinicalTrials.gov records, only 123 records (25%) reported a number for deaths. Reporting of deaths across data modules for participant flow, primary or secondary outcomes and serious adverse events was variable. In a sample of 27 pairs of ClinicalTrials.gov records with number of deaths and corresponding publications, total deaths per arm could only be determined in 56% (15/27 pairs) but were discordant in 19% (5/27). In 27 pairs of ClinicalTrials.gov records without any information on number of deaths, 48% (13/27) were discordant since the publications reported absence of deaths in 33% (9/27) and positive death numbers in 15% (4/27). Deaths are variably reported in ClinicalTrials.gov records. A reliable total number of deaths per arm cannot always be determined with certainty or can be discordant with number reported in corresponding trial publications. This highlights a need for unambiguous and complete reporting of the number of deaths in trial registries and publications.


Evidence of infection with Leptospira interrogans and spotted fever group rickettsiae among rodents in an urban area of Osaka City, Japan.
We examined 33 rodents captured in an urban area of Osaka City, Japan for IgG antibodies against Seoul virus, severe fever with thrombocytopenia syndrome virus, hepatitis E virus, Leptospira interrogans, Yersinia pestis, spotted fever, typhus and scrub typhus group rickettsiae. We found that 3 (9.1%) and 1 (3.0%) of the 33 rodents had antibodies against L. interrogans and spotted fever group rickettsiae, respectively. DNAs of leptospires were detected from 2 of the 3 seropositive rodents, but DNA of rickettsia was not detected. Phylogenetic analysis and multiple locus sequence typing revealed that the 2 leptospires were L. interrogans belonging to a novel sequence type. There is a potential risk for acquiring rodent-borne zoonotic pathogens even in cities in developed countries.


Phytol, a diterpene alcohol from chlorophyll, as a drug against neglected tropical disease Schistosomiasis mansoni.
Schistosomiasis is a major endemic disease that affects hundreds of millions worldwide. Since the treatment and control of this parasitic disease rely on a single drug, praziquantel, it is imperative that new effective drugs are developed. Here, we report that phytol, a diterpene alcohol from chlorophyll widely used as a food additive and in medicinal fields, possesses promising antischistosomal properties in vitro and in a mouse model of schistosomiasis mansoni. In vitro, phytol reduced the motor activity of worms, caused their death and confocal laser scanning microscopy analysis showed extensive tegumental alterations in a concentration-dependent manner (50 to 100 µg/mL). Additionally, phytol at sublethal doses (25 µg/mL) reduced the number of Schistosoma mansoni eggs. In vivo, a single dose of phytol (40 mg/kg) administered orally to mice infected with adult S. mansoni resulted in total and female worm burden reductions of 51.2% and 70.3%, respectively. Moreover, phytol reduced the number of eggs in faeces (76.6%) and the frequency of immature eggs (oogram pattern) was significantly reduced. The oogram also showed increases in the proportion of dead eggs. Confocal microcopy studies revealed tegumental damage in adult S. mansoni recovered from mice, especially in female worms. The significant reduction in parasite burden by this chlorophyll molecule validates phytol as a promising drug and offers the potential of a new direction for chemotherapy of human schistosomiasis. Phytol is a common food additive and nonmutagenic, with satisfactory safety. Thus, phytol has potential as a safe and cost-effective addition to antischistosomal therapy.


trans-Beta-nitrostyrene derivatives as slow-binding inhibitors of protein tyrosine phosphatases.
Protein tyrosine phosphatases (PTPs) catalyze the hydrolysis of phosphotyrosyl (pY) proteins to produce tyrosyl proteins and inorganic phosphate. Specific PTPs inhibitors provide useful tools for studying PTP function in signal transduction processes and potential treatment for human diseases such as diabetes, inflammation, and cancer. In this work, trans-beta-nitrostyrene (TBNS) and its derivatives are found to be slow-binding inhibitors against protein tyrosine phosphatases PTP1B, SHP-1, and Yop with moderate potencies (K(I*) = 1-10 microM). Competition experiments with a substrate (pNPP) and iodoacetate indicate that TBNS is active site-directed. The mechanism of inhibition was investigated by UV-vis absorption spectroscopy, (1)H-(13)C heteronuclear single-quantum correlation NMR spectroscopy, and site-directed mutagenesis. These studies suggested a mechanism in which TBNS acts a pY mimetic and binds to the PTP active site to form an initial noncovalent E.I complex, followed by nucleophilic attack on the TBNS nitro group by Cys-215 of PTP1B to form a reversible, covalent adduct as the tighter E.I* complex. TBNS derivatives represent a new class of neutral pY mimetic inhibitors of PTPs.


A massive bleeding from a gastrointestinal stromal tumor of a Meckel's diverticulum.
Meckel's diverticulum is the most common congenital anomaly of the gastro intestinal tract, present in about 2% of population. The article presents the case of a 44-year-old otherwise healthy man with anemia, who was diagnosed lower gastrointestinal bleeding. An abdominal CT scan revealed a clearly demarcated solid tumor in hypogastric region, measuring 65 x 45 mm. A laparotomy through lower midline incision was performed. A surgical resection of a lesion of a Meckel's diverticulum was carried out and a final diagnosis of gastrointestinal stromal tumor was made.The patient made an uneventful recovery. The preoperative diagnosis of a complicated Meckel's diverticulum may be challenging. CT is usually an adequate method to diagnose tumors arising from Meckel's diverticulum.


Serum sodium levels and related treatment-emergent adverse events during eslicarbazepine acetate use in adults with epilepsy.
To examine the frequency of hyponatremia and potentially related symptoms in clinical trials of eslicarbazepine acetate (ESL) in adults with focal- (partial-) onset seizures. This post hoc, exploratory analysis included data from three controlled phase 3 trials of adjunctive ESL (400-1200 mg once daily), two phase 3 trials of ESL monotherapy (1200-1600 mg once daily), and their open-label extension studies. Exploratory endpoints included clinical laboratory measurements of serum sodium concentrations ([Na+ ]), incidences of hyponatremia-related treatment-emergent adverse events (TEAEs), and incidences of TEAEs that are potential symptoms of hyponatremia. The controlled trials of adjunctive ESL and ESL monotherapy included 1447 (placebo, n = 426; ESL, n = 1021) and 365 (ESL, n = 365) patients, respectively; 639 and 274 patients continued onto uncontrolled, open-label extensions. In the controlled and uncontrolled trials ≤3.3% of patients taking ESL had a minimum postdose [Na+ ] measurement ≤125 mEq/L, <9% had a >10 mEq/L decrease in [Na+ ] from baseline, <6% had a hyponatremia-related TEAE, and <2% discontinued the controlled trials due to a hyponatremia-related TEAE. Hyponatremia appeared to be more frequent in the monotherapy (vs adjunctive therapy) trials; in the controlled trials of adjunctive ESL and ESL monotherapy, incidence generally increased with increasing ESL dose. The majority of patients with an investigator-reported TEAE of "hyponatremia" or "blood sodium decreased" did not have a corresponding laboratory [Na+ ] measurement ≤125 mEq/L. Some symptoms potentially related to hyponatremia (including nausea and vomiting) were more frequent in patients with a minimum postdose [Na+ ] measurement ≤125 mEq/L. Reductions in serum sodium concentrations and hyponatremia-related TEAEs occurred in a small number of patients taking ESL. Suspected hyponatremia should be confirmed and monitored via [Na+ ] measurements.


Comparison of Automatic Segmentation Algorithms for the Subthalamic Nucleus.
Various automatic segmentation algorithms for the subthalamic nucleus (STN) have been published recently. However, most of the available software tools are not approved for clinical use. The aim of this study is to evaluate a clinically available automatic segmentation tool of the navigation planning software Brainlab Elements (BL-E) by comparing the output to manual segmentation and a nonclinically approved research method using the DISTAL atlas (DA) and the Horn electrophysiological atlas (HEA). Preoperative MRI data of 30 patients with idiopathic Parkinson's disease were used, resulting in 60 STN segmentations. The segmentations were created manually by two clinical experts. Automatic segmentations of the STN were obtained from BL-E and Advanced Normalization Tools using DA and HEA. Differences between manual and automatic segmentations were quantified by Dice and Jaccard coefficient, target overlap, and false negative/positive value (FNV/FPV) measurements. Statistical differences between similarity measures were assessed using the Wilcoxon signed-rank test with continuity correction, and comparison with interrater results was performed using the Mann-Whitney U test. For manual segmentation, the mean size of the segmented STN was 133 ± 24 mm3. The mean size of the STN was 121 ± 18 mm3 for BL-E, 162 ± 21 mm3 for DA, and 130 ± 17 mm3 for HEA. The Dice coefficient for the interrater comparison was 0.63 and 0.54 ± 0.12, 0.59 ± 0.13, and 0.52 ± 0.14 for BL-E, DA, and HEA, respectively. Significant differences between similarity measures were found for Dice and Jaccard coefficient, target overlap and FNV between BL-E and DA; and FPV between BL-E and HEA. However, none of the differences were significant compared to interrater variability. The analysis of the center of gravity of the segmentations revealed that the BL-E STN ROI was located more medially, superior and posterior compared to other segmentations. Regarding the target overlap for beta power within the STN ROI included with the HEA, the BL-E segmentation showed a significantly higher value compared to manual segmentation. Automatic image segmentation by means of the clinically approved software BL-E provides STN segmentations with similar accuracy like research tools, and differences are in the range of observed interrater variability. Further studies are required to investigate the clinical validity, for example, by comparing segmentation results of BL-E with electrophysiological data.


Preparation of polyelectrolyte-coated pH-sensitive poly(styrene) microcapsules and their application to initiation-cessation control of an enzyme reaction.
Poly(styrene) microcapsules, prepared by depositing the polymer around emulsified aqueous droplets, were coated with a synthesized polyelectrolyte; i.e., copolymer of maleic acid (MA) with methyl vinyl ether (MVE), co-poly(MA, MVE), or with styrene (St), copoly(Ma, St). The permeability of the capsule membrane was investigated under various pHs of the outer medium using n-propyl alcohol as a permeant. It became apparent that either copoly(MA, St)- or copoly(MA, MVE)-coated microcapsules function as a pH-sensitive capsule. In particular, the former showed a dramatic change of the permeability in response to small differences in pH (5-6). By reference to the viscometric and electrophoretic studies of both copolymers, these were interpreted as being due to a pH-induced alteration of the configuration of the copolymer coating on the surface of the capsule membrane. When sucrose was hydrolyzed in an aqueous suspension of the copoly(MA, St)-coated capsules into which invertase was loaded, the hydrolytic reaction was initiated at pH 5. 5 and stopped at pH 4. 5. Such initiation-cessation control was repeated reversibly without damaging the capsules.


Golgi-bound Rab34 is a novel member of the secretory pathway.
Golgi-localized Rab34 has been implicated in repositioning lysosomes and activation of macropinocytosis. Using HeLa cells, we undertook a detailed investigation of Rab34 involvement in intracellular vesicle transport. Immunoelectron microscopy and immunocytochemistry confirmed that Rab34 is localized to the Golgi stack and that active Rab34 shifts lysosomes to the cell center. Contrary to a previous report, we found that Rab34 is not concentrated at membrane ruffles and is not involved in fluid-phase uptake. Also, Rab34-induced repositioning of lysosomes does not affect mannose 6-phosphate receptor trafficking. Most strikingly, HeLa cells depleted of Rab34 by transfection with dominant-negative Rab34 or after RNA interference, failed to transport the temperature-sensitive vesicular stomatitis virus G-protein (VSVG) fused to green fluorescent protein (VSVG-GFP) from the Golgi to the plasma membrane. Transfection with mouse Rab34 rescued this defect. Using endogenous major histocompatibility complex class I (MHCI) as a marker, an endoglycosidase H resistance assay showed that endoplasmic reticulum (ER) to medial Golgi traffic remains intact in knockdown cells, indicating that Rab34 specifically functions downstream of the ER. Further, brefeldin A treatment revealed that Rab34 effects intra-Golgi transport, not exit from the trans-Golgi network. Collectively, these results define Rab34 as a novel member of the secretory pathway acting at the Golgi.


RNAi screening uncovers Dhx9 as a modifier of ABT-737 resistance in an Eμ-myc/Bcl-2 mouse model.
ABT-737 is a promising chemotherapeutic agent that promotes apoptosis by acting as a selective BH3 mimetic to neutralize Bcl-2-like family members. One shortcoming with its use is that Mcl-1, a member of the Bcl-2 family, is poorly inhibited by ABT-737 and thus is a major cause of resistance. We performed a short hairpin RNA (shRNA)-based drop-out screen to identify novel genes and pathways that could reverse resistance to ABT-737 treatment in Eµ-myc/Bcl-2 lymphoma cells engineered to rely on endogenous Mcl-1 for survival. Several drug-sensitive shRNAs were identified that were selectively depleted in the presence of ABT-737. Of these, 2 independent shRNAs targeting the RNA/DNA helicase Dhx9 were found to sensitize lymphomas to ABT-737 to an extent comparable to control Mcl-1 shRNAs. Although Dhx9 suppression sensitized both mouse and human cells to ABT-737 treatment, it did so without altering MCL-1 levels. Rather, loss of Dhx9 appeared to activate a p53-dependent apoptotic program, through aggravation of replicative stress, which was found to be both necessary and sufficient for the ABT-737-shDhx9 synthetic lethal relationship.


Genomic profiling of patient-derived colon cancer xenograft models.
Recent evidence suggests that patient derived xenograft (PDX) models can maintain certain pathological and molecular features of the original disease. However, these characterizations are limited to immunohistochemistry or by tissue microarray analysis. We conducted a high-throughput sequencing of primary colon tumor and PDX has not been reported yet. Fresh primary colon cancer tissues that originate from surgery were implanted into the subcutaneous space of 6- to 8-week-old female BALB/c nu/nu or NOD/SCID mice and serially passaged in vivo. Ion AmpliSeq Cancer Hotspot Panel v2 (Ion Torrent) was used to detect frequent somatic mutations and similarity of molecular characteristics between the 10 patient tumors and matched PDX. Histologic and immunohistochemical analyses revealed a high degree of pathologic similarity including histologic architecture and expression of CEA, CK7, and CD20 between the patient and xenograft tumors. In 80% cases, all of the somatic mutations detected in primary tumor were concordantly detected in PDX models. However, 2 PDX models showed gained mutations such as PIK3CA or FBWX7 mutation. Ten patient-derived advanced colon cancer xenograft models were established. These models maintained the key characteristic features of the original tumors, suggesting useful tool for preclinical personalized medicine platform.


Young Mexicans' hopes and fears about abortion and abortion law: a qualitative study in two cities.
In Mexico, abortion is legal only in limited, specific circumstances and unsafe abortion complications are estimated to be the fourth leading cause of maternal mortality. Our study sought to understand the opinions Mexicans hold about abortion and sexuality and to learn about their fears and hopes about more liberalized abortion laws in Mexico. We carried out 12 focus groups with a total of 87 women and men, aged 18-24. Six focus groups took place in Mexico City and six in Merida, Yucatan. One reader thematically analyzed and coded discussion transcripts. Participants favoring highly restrictive abortion laws generally felt that pregnant women should "face the consequences" of having a baby, whereas those who favored less restrictive laws focused less on culpability and more on the woman's right to control her future. Mexico City participants generally had more liberal abortion opinions. Most Merida participants thought abortion was never legal, despite the fact that their state has the country's most liberal abortion laws. Many felt that, if abortion were legal, there would be more abortions but that it would likely be a safer procedure. Merida participants' more conservative attitudes may be a reflection of their lower educational levels and largerproportion of Catholic participants compared to the Mexico City groups. It is critical to introduce more balanced information that emphasizes the safety of abortions performed under legal conditions and address fears of greatly elevated abortion rates if abortion laws were liberalized. Mexican young adults need more scientific, balanced sources of information on abortion and abortion law.


Novel Alzheimer's disease genes and epistasis identified using machine learning GWAS platform.
Alzheimer's disease (AD) is a complex genetic disease, and variants identified through genome-wide association studies (GWAS) explain only part of its heritability. Epistasis has been proposed as a major contributor to this 'missing heritability', however, many current methods are limited to only modelling additive effects. We use VariantSpark, a machine learning approach to GWAS, and BitEpi, a tool for epistasis detection, to identify AD associated variants and interactions across two independent cohorts, ADNI and UK Biobank. By incorporating significant epistatic interactions, we captured 10.41% more phenotypic variance than logistic regression (LR). We validate the well-established AD loci, APOE, and identify two novel genome-wide significant AD associated loci in both cohorts, SH3BP4 and SASH1, which are also in significant epistatic interactions with APOE. We show that the SH3BP4 SNP has a modulating effect on the known pathogenic APOE SNP, demonstrating a possible protective mechanism against AD. SASH1 is involved in a triplet interaction with pathogenic APOE SNP and ACOT11, where the SASH1 SNP lowered the pathogenic interaction effect between ACOT11 and APOE. Finally, we demonstrate that VariantSpark detects disease associations with 80% fewer controls than LR, unlocking discoveries in well annotated but smaller cohorts.


N-3 PUFAs and their specialized pro-resolving lipid mediators on airway inflammatory response: beneficial effects in the prevention and treatment of respiratory diseases.
Respiratory diseases include a wide range of pathologies with different clinical manifestations, affecting the normal airways and lung function. An increase in the inflammatory response is considered a characteristic hallmark of these diseases, being also a critical factor for their progression. The n-3 polyunsaturated fatty acids (n-3 PUFAs) eicosapentaenoic acid (C20:4n-3, EPA), docosahexaenoic acid (C22:6n-3, DHA) and their lipid mediators are known to have an inflammation pro-resolution effect. The effects of these n-3 PUFAs in the prevention and treatment of respiratory diseases are beginning to be understood. Consequently, this article aims to analyze the influence of n-3 PUFAs and their lipid mediators on the inflammatory response in respiratory health, emphasizing recent data concerning their beneficial effects in the prevention and possible treatment of different respiratory diseases, particularly asthma, airway allergic syndromes and chronic obstructive pulmonary disease. The review includes studies regarding the effects of EPA, DHA, and their specialized pro-resolving lipid mediators (SPMs) on in vivo and in vitro models of respiratory disease, concluding that EPA and DHA have a positive impact in attenuating the pro-inflammatory response in respiratory diseases, reducing symptoms like nasal congestion, fever and difficulty in breathing. Controversial data reported are probably due to differences in several factors, including the dosages, administration vehicles, and the supplementation times employed, which are aspects that remain to be addressed in future studies.


Trimethoprim-sulfamethoxazole-induced hyperkalemia in a patient with normal renal function.
The authors present a case of Trimethoprim-sulfamethoxazole-induced hyperkalemia in a patient with normal renal function. While toxicity of this drug has been reported in patients with renal insufficiency, this case highlights the toxicity associated with normal kidney function. Due to its popularity in the medical field and to the largely unrecognized effect of hyperkalemia, it is important to consider such adverse effects when prescribing TMX-SMX. One must be reminded of the possibility of the development of life-threatening hyperkalemia in relatively healthy patients.


Electrostatic association of glutathione transferase to the nuclear membrane. Evidence of an enzyme defense barrier at the nuclear envelope.
The possible nuclear compartmentalization of glutathione S-transferase (GST) isoenzymes has been the subject of contradictory reports. The discovery that the dinitrosyl-diglutathionyl-iron complex binds tightly to Alpha class GSTs in rat hepatocytes and that a significant part of the bound complex is also associated with the nuclear fraction (Pedersen, J. Z., De Maria, F., Turella, P., Federici, G., Mattei, M., Fabrini, R., Dawood, K. F., Massimi, M., Caccuri, A. M., and Ricci, G. (2007) J. Biol. Chem. 282, 6364-6371) prompted us to reconsider the nuclear localization of GSTs in these cells. Surprisingly, we found that a considerable amount of GSTs corresponding to 10% of the cytosolic pool is electrostatically associated with the outer nuclear membrane, and a similar quantity is compartmentalized inside the nucleus. Mainly Alpha class GSTs, in particular GSTA1-1, GSTA2-2, and GSTA3-3, are involved in this double modality of interaction. Confocal microscopy, immunofluorescence experiments, and molecular modeling have been used to detail the electrostatic association in hepatocytes and liposomes. A quantitative analysis of the membrane-bound Alpha GSTs suggests the existence of a multilayer assembly of these enzymes at the outer nuclear envelope that could represent an amazing novelty in cell physiology. The interception of potentially noxious compounds to prevent DNA damage could be the possible physiological role of the perinuclear and intranuclear localization of Alpha GSTs.


Haemoproteus minutus is highly virulent for Australasian and South American parrots.
Haemoproteus and Plasmodium species are widespread avian blood parasites. Several Plasmodium species are known for their high virulence and have caused significant declines in naïve bird populations. The impact of closely related Haemoproteus parasites is largely unknown. Recently we reported a lethal disease in two parrot aviaries caused by Haemoproteus parasites. Here we show that the causative pathogen Haemoproteus minutus is responsible for further 17 lethal outbreaks in parrot aviaries in Denmark, Germany and Great Britain. All affected parrots are endemic to Australasia and South America. We sequenced the cytochrome b gene from megalomeront-infected muscle tissue of 21 parrots and identified the two lineages TUPHI01 and TURDUS2 as causative agents, commonly naturally infecting the common blackbird (Turdus merula) and the song thrush (Turdus philomelos), respectively, in the Palaearctic. No intraerythrocytic parasite stages were found in any of the parrots. We failed to detect H. minutus in invasive Indian ring-necked parakeets (Psittacula krameri) in Germany. Together this suggests that abortive infections with two virulent lineages of H. minutus are lethal for naïve parrot species from Australasia and South America. We asked whether we could detect H. minutus in New Zealand, where its Turdus hosts were introduced in the 1800s. We therefore tested invasive blackbirds and song thrushes, and the co-existing endemic red-fronted parakeet (Cyanoramphus novaezelandiae) population on three New Zealand islands. No Haemoproteus spp. DNA was detected in all blood samples, indicating absence of transmission. The results of this study show that captive parrots in Europe are threatened by two lineages of an otherwise benign parasite of Turdus spp. Aviary collections of parrots should be protected from Culicoides spp. vectors in Europe. Animal trade and climate changes extending the current vector and parasite distribution have to be considered as potential risk factors for the introduction of the disease in naïve parrot populations.


Developmental dynamics of stem starch accumulation in Sorghum bicolor.
Sweet sorghums were identified that accumulate up to ~9% of their total stem dry weight as starch. Starch accumulated preferentially in stem pith parenchyma in close proximity to vascular bundles. Stem starch accumulated slowly between floral initiation and anthesis and more rapidly between anthesis and 43 days post-anthesis before declining in parallel with tiller outgrowth. Genes involved in stem starch metabolism were identified through phylogenetic approaches and RNA-seq analysis of Della stem gene expression during the starch accumulation phase of development. Genes differentially expressed in stems were identified that are involved in starch biosynthesis (i.e., AGPase SS/LS, starch synthases, starch-branching enzymes), degradation (i.e., glucan-water dikinase, β-amylase, disproportionating enzyme, alpha-glucan phosphorylase) and amyloplast sugar transport (glucose-6-P translocator). Transcripts encoding AGPase SS and LS subunits with plastid localization were differentially induced during stem starch accumulation indicating that ADP-glucose for starch biosynthesis is primarily generated in stem plastids. Cytosolic heteroglucan metabolism may play a role in stem sucrose/starch accumulation because genes encoding cytosolic forms of the disproportionating enzyme and alpha-glucan phosphorylase were induced in parallel with stem sucrose/starch accumulation. Information on the stem starch pathway obtained in this study will be useful for engineering sorghum stems with elevated starch thereby improving forage quality and the efficiency of biomass conversion to biofuels and bio-products.


Framework for morphometric classification of cells in imaging flow cytometry.
Imaging flow cytometry is an emerging technology that combines the statistical power of flow cytometry with spatial and quantitative morphology of digital microscopy. It allows high-throughput imaging of cells with good spatial resolution, while they are in flow. This paper proposes a general framework for the processing/classification of cells imaged using imaging flow cytometer. Each cell is localized by finding an accurate cell contour. Then, features reflecting cell size, circularity and complexity are extracted for the classification using SVM. Unlike the conventional iterative, semi-automatic segmentation algorithms such as active contour, we propose a noniterative, fully automatic graph-based cell localization. In order to evaluate the performance of the proposed framework, we have successfully classified unstained label-free leukaemia cell-lines MOLT, K562 and HL60 from video streams captured using custom fabricated cost-effective microfluidics-based imaging flow cytometer. The proposed system is a significant development in the direction of building a cost-effective cell analysis platform that would facilitate affordable mass screening camps looking cellular morphology for disease diagnosis.


The effects of promoter variations of the N-Methylcanadine 1-Hydroxylase (CYP82Y1) gene on the noscapine production in opium poppy.
Noscapine is an antitumor alkaloid produced in opium poppy (Papaver somniferum) and some members of the Papaveraceae family. It has been primarily used for its antitussive effects; more recently, its anticancer properties were shown. Herein, we detected an SSR embedded in the promoter region of the CYP82Y1 gene, which was found to be the first committed-step enzyme in the noscapine biosynthesis pathway, using the MISA program. Some collected ecotypes of P. somniferum were investigated for understanding of SSRs role in the regulation of gene expression and metabolite content. Quantitative PCR showed that a variation in the motif repeat number (either a decrease or increase) down-regulated the expression of the CYP82Y1 gene. Furthermore, the analysis of noscapine content suggested that a variation in the promoter region influence noscapine amount. Moreover, P. bracteatum was analyzed in both transcript and metabolite levels, and illustrated much less expression and metabolite level in comparison to P. somniferum. By exploiting the transcriptome data from the eight genera of the Papaveraceae family, we found that noscapine biosynthesis genes are present in P. bracteatum and are not shared in other genera of the Papaveraceae family. This results may explain production of a confined metabolite within a genus.


Apolipoprotein ε7 allele in memory complaints: insights through protein structure prediction.
APOE ε7 gene is a rare mutant form of APOE ε3. The mutation occurs in the lipid-binding domain of APOE. Based on the protein's structure, APOE ε7 is expected to function in lipid and β-amyloid metabolism, similar to APOE ε4. However, unlike that for APOE ε4, the mechanisms responsible for Alzheimer's disease (AD) cases associated with APOE ε7 expression have not been elucidated. The present study aims to investigate the association between APOE ε7 expression and cognitive impairment. APOE was sequenced in DNA samples collected from 344 memory-complaint patients who visited the memory clinic, and from 345 non-memory-complaint individuals from the health promotion center. The protein structures of ApoE3, ApoE4, and ApoE7 were predicted. Three ε3/ε7 heterozygote individuals who were all classified under the memory-complaint group were identified. Of these, two subjects were clinically diagnosed with AD with small vessel disease, and the remaining individual was diagnosed with subjective cognitive impairment. This study predicted the protein structures of ApoE3, ApoE4, and ApoE7 and determined the three-dimensional structure of the carboxy terminus of ApoE7, which participates in an electrostatic domain interaction similar to that of APOE ε4. APOE K244 or K245 mutations for APOE ε7 were not found in the Korean reference genome database, which contains information (http://126.96.36.199/KRGDB/browser/mainBrowser.jsp) from 622 healthy individuals. As verified by the results of structural prediction, APOE ε7 could serve as another risk factor for cognitive impairment and is particularly associated with vascular disease. However, additional studies are required to validate the pathogenic nature of APOE ε7.


Chromone derivatives, R- and S- taeniolin, from the marine-derived fungus Taeniolella sp. BCC31839.
Two unknown enantiomeric compounds, named (R)- and (S)-taeniolin, along with six known compounds, were isolated from the marine-associated fungus Taeniolella sp. BCC31839. Chemical structures were determined by NMR spectroscopic techniques, and the absolute configurations were confirmed by Mosher application together with CD spectral analyses. Both were inactive for antimicrobial activity against multidrug-resistant malaria parasite (Plasmodium falciparum) and bacteria (Mycobacerium tuberculosis and Bacillus cereus) at maximum tested concentration.


Evaluation of Eating Attitude in Patients with Migraine.
This study aimed to investigate the eating attitudes in patients with migraine. Fifty-nine patients (mean age: 32.54±8.47 years) diagnosed with migraine according to the International Classification of Headache Disorder, 2004, and 47 age-, gender- and education-matched healthy controls (mean age: 31.85±7.14 years) were enrolled for this study. Sociodemographic data were recorded, and the body mass index was calculated as kilograms per meter squared. Data regarding the duration of illness and attack, frequency of migraine attacks, and the presence of aura were recorded. Migraine severity was assessed by Migraine Disability Assessment Score (MIDAS). Eating Attitudes Test (EAT), Beck Depression Inventory (BDI), and Beck Anxiety Inventory were applied to all participants. The patients with migraine had significantly higher EAT scores, levels of anxiety, and depression than controls (p<.01). Furthermore, 11.9% of patients with migraine had an EAT score of 30 or higher, which is suggestive of a disordered eating attitude, whereas this rate was 2.1% in healthy controls (p<.05). The scores of EAT and BDI had positive correlation with the scores of MIDAS in patients with migraine (r=.298, p<.05; r=.332, p=.01, respectively). In our study, disordered eating attitudes and the levels of anxiety and depression were high in patients with migraine than controls. Our study is important to demonstrate the connection between migraine and disordered eating attitudes.


The use of continuous vs. intermittent cold water immersion as a recovery method in basketball players after training: a randomized controlled trial.
The main objective of this study was to compare two cold water immersion protocols, continuous or intermittent, on recovery in basketball players. Ten male basketball players (age: 14 ± 0.4 years, body mass: 65.4 ± 9.1 kg, height: 175 ± 7.3 cm, body fat %: 10.3 ± 4) were included in the study. After three 90-minute training sessions (avg. heart rate 158 ± 11.92, 156 ± 7.06 and 151 ± 10.44 bpm), participants were grouped into a continuous immersion (12 min at 12 ± 0.4°C) group, intermittent immersion (4 x 2 min immersion at 12 ± 0.4 °C + 1 min out of water) group and a control group (CG). Countermovement jump (CMJ), muscle pain and thigh volume were measured. Both cold water immersion protocols were effective in reducing the pain 24 and 48 hours after training compared with the CG (F (3.54) = 2.91, p = 0.016, ηp2 = .24). Concerning CMJ change, % differences occurred at 24 (Z = 11.04, p = 0.004) and 48 hours (Z = 14.01, p < 0.001) in comparison with the CG. Regarding the muscle volume, the statistical analysis did not report a significant interaction (F (3.54) = 2.42, p = 0.058). Both cold water immersion CWI protocols are effective in improving recovery in basketball players.


Percutaneous balloon aortic valvuloplasty at the Queen Sirikit National Institute of Child Health: 25 years' experience.
Percutaneous balloon aortic valvuloplasty (BAV) is the treatment of choice in moderate and severe valvular aortic stenosis. In Thailand, the first procedure was performed at the Queen Sirikit National Institute of Child Health (QSNICH) in 1988. No previous studies have been reported regarding the outcome of these procedures at QSNICH. To study the efficacy and complications of percutaneous balloon aortic valvuloplasty in the treatment of severe aortic stenosis. A retrospective study from the medical records was performed. All patients with a diagnosis of moderate or severe valvular aortic stenosis treated with BAV from January 1988-December 2012 were recruited. Before 2008, the procedures were performed under local anesthesia with light systemic sedation. After that, most of the cases were performed under general anesthesia. The response to treatment was classified as good response, partial response or failure. The short-term complications were classified as vascular complications, arrhythmias and others. Sixty-eight recorded attempts on 60 patients (47 males = 71.67%) were enlisted in the study. The ages at the time of procedures ranged from 1 day to 15 years (mean 65.25, SD 53.54, median 51 months). Fourteen cases were under one year of age (20.58%). Immediate success comprised 85.29% with 65.51% classified as good response. Ten failures in nine cases all occurred before 1997. One of the cases was an attempted balloon aortic valvuloplasty with repeated failure. Three of the cases underwent open aortic valvuloplasty where one case (33.33%) survived. The other six cases refused to continue treatment and were lost to follow-up. Four deaths were reported. Repeated balloon aortic valvuloplasties were performed in eight cases. During the early phases (1988-1996), failures and mortality rates were extremely high. Experience and improved technology improved outcomes. Excluding the four dead cases, the only significant major complication occurred in a three-year-old boy with severe aortic stenosis who tore the chordae tendinae, producing severe, acute mitral regurgitation, together with ventricular tachycardia, requiring direct current cardioversion during the procedure and double valvuloplasty five years later. Other minor complications included transient cardiac arrhythmia in 12 cases, partial occlusion of femoral artery in 11 cases and groin hematoma in 8 cases. Percutaneous balloon aortic valvuloplasty was effective and safe for the treatment of moderate and severe aortic valve stenosis in pediatric patients without significant complications.


Changes in utilization of TB health services in Nepal.
Nepal. To assess the impact of community mobilization and health worker training on tuberculosis (TB) health services utilization. Questionnaire. The Japan International Cooperation Agency and the Nepal Ministry of Health launched a set of interventions to increase awareness and availability of treatment at government facilities. In 2001 and 2003, a questionnaire was administered to TB patients. In 2001-2002, 77.3% of women and 80.0% of men with TB symptoms consulted at government facilities, compared to 30% of men and 32% of women in 1997-1999. In the absence of any secular causes, this change can be attributed to the increasing community awareness of availability and quality of DOTS.


Greater Acute Concussion Symptoms Are Associated With Longer Recovery Times in NCAA Division III Collegiate Athletes.
We examined the association between the severity of acute concussion symptoms and time to return to school and to sports in National Collegiate Athletic Association (NCAA) Division III collegiate athletes. We hypothesized that students with the lowest burden of acute symptoms, measured in the first 72 h, would have the fastest return to school and sports and those with the highest burden of symptoms would have the slowest return to school and sports. This injury surveillance cohort included 808 athletes from 11 NCAA Division III colleges who sustained a concussion between 2014 and 2019. Athletic trainers documented time to return to school and to sports. Kruskal-Wallis tests with post-hoc planned comparison Mann-Whitney U tests were used to assess whether athletes took longer to return based on their acute symptom burden (Low, Medium, or High). Survival analysis (Kaplan Meier with log rank tests) was used to compare the recovery times based on acute symptom burden (censored at 28 days). Chi-square tests compared the proportion of those who had not yet returned to school or sports at various recovery benchmarks (i.e., 1 week, 10 days, 2 weeks, 3 weeks, 4 weeks) based on acute symptom burden. Women (median = 5 days) took slightly longer than men (median = 4 days) to return to school (p = 0.001; r = -0.11, small effect). Women and men did not differ on time to return to sports (p = 0.32, r = -0.04). A greater proportion with high acute symptoms remained out of school at 5 (odds ratio, OR = 4.53), 7 (OR = 4.98), and 10 (OR = 4.80) days compared to those with low acute symptoms. A greater proportion with high acute symptoms remained out of sports at 10 (OR = 4.11), 14 (OR = 3.46), and 21 (OR = 3.01) days compared to those with low acute symptoms. This study shows a strong association between having a high burden of acute post-concussion symptoms and having a slower return to school and sports in Division III collegiate athletes. Moreover, it also illustrates the converse: that those athletes with a low burden of acute symptoms have a faster return to school and sports.


Subjective appraisal of threat (criterion A2) as a predictor of distress in childbearing women.
Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, has removed criterion A2 from the diagnosis of posttraumatic stress disorder. The current study aimed to assess the claim that criterion A2 has low use in predicting distress, while addressing the shortcomings of previous research looking at criteria A1 and A2. Data from a longitudinal, prospective study was used, with 933 women having been assessed at four time points both prebirth and postbirth. In our sample of women, model comparisons suggest that criterion A2 should be reintroduced into the diagnostic criteria as it provides a better indicator of who goes on to have problems after giving birth than criterion A1 on its own. There is also evidence that this subjective reaction to event confrontation (A2) should include anger, shame, and guilt.


Diffusion-Weighted Magnetic Resonance Imaging Characterization of White Matter Injury Produced by Axon-Sparing Demyelination and Severe Contusion Spinal Cord Injury in Rats.
Alterations in magnetic resonance imaging (MRI)-derived measurements of water diffusion parallel (D∥) and perpendicular (D⊥) to white matter tracts have been specifically attributed to pathology of axons and myelin, respectively. We test the hypothesis that directional diffusion measurements can distinguish between axon-sparing chemical demyelination and severe contusion spinal cord white matter injury. Adult rats received either unilateral ethidium bromide (EB) microinjections (chemical demyelination) into the lateral funiculus of the spinal cord at C5 or were subjected to unilateral severe contusion spinal cord injury (SCI). Diffusion MRI metrics in the lateral funiculus were analyzed at early and late time-points following injury and correlated with histology. Early EB-demyelination resulted in a significant elevation in D⊥ and significant reduction in D∥ at the injury epicenter, with histological evidence of uniform axon preservation. Alterations in D⊥ and D∥ at the epicenter of early EB-demyelination were not significantly different from those observed with severe contusion at the epicenter, where histology demonstrated severe combined axonal and myelin injury. Diffusion abnormalities away from the injury epicenter were seen with contusion injury, but not with EB-demyelination. Chronic EB lesions underwent endogenous remyelination with normalization of diffusion metrics, whereas chronic contusion resulted in persistently altered diffusivities. In the early setting, directional diffusion measurements at the injury epicenter associated with chemical demyelination are indistinguishable from those seen with severe contusive SCI, despite dramatic pathologic differences between injury models. Caution is advised in interpretation of diffusion metrics with respect to specific white matter structural alterations. Diffusion analysis should not be limited to the epicenter of focal spinal lesions as alterations marginal to the epicenter are useful for assessing the nature of focal white matter injury.


Task Assignment and Path Planning for Multiple Autonomous Underwater Vehicles Using 3D Dubins Curves †.
This paper investigates the task assignment and path planning problem for multiple AUVs in three dimensional (3D) underwater wireless sensor networks where nonholonomic motion constraints of underwater AUVs in 3D space are considered. The multi-target task assignment and path planning problem is modeled by the Multiple Traveling Sales Person (MTSP) problem and the Genetic Algorithm (GA) is used to solve the MTSP problem with Euclidean distance as the cost function and the Tour Hop Balance (THB) or Tour Length Balance (TLB) constraints as the stop criterion. The resulting tour sequences are mapped to 2D Dubins curves in the X - Y plane, and then interpolated linearly to obtain the Z coordinates. We demonstrate that the linear interpolation fails to achieve G 1 continuity in the 3D Dubins path for multiple targets. Therefore, the interpolated 3D Dubins curves are checked against the AUV dynamics constraint and the ones satisfying the constraint are accepted to finalize the 3D Dubins curve selection. Simulation results demonstrate that the integration of the 3D Dubins curve with the MTSP model is successful and effective for solving the 3D target assignment and path planning problem.


Sexuality in aging: implications for nursing facility staff.
Sexuality is an area that is frequently overlooked by staff who work with the elderly in nursing facilities. The nursing literature supports a need for education of nursing facility staff about sexual issues and concerns of facility residents. This article describes the effect of an educational intervention on one sample of facility staff and recommends strategies for the education and practice of staff members employed in nursing facilities.


[Metabolic disorders in renal transplant recipients].
Advancements in immunosuppressive treatment of renal transplant recipients have significantly increased the graft and patient survival and significantly lowered the incidence of rejection crises. Efforts to increase long term patient and graft survival are directed to the prevention and treatment of cardiovascular diseases because they are the leading cause of mortality in these patients. Traditional risk factors for the development of cardiovascular diseases (e.g., arterial hypertension, posttransplant diabetes mellitus and metabolic lipid disorder) are up to fifty times more frequent among renal transplant recipients than in the general population. The goal of this study was to analyze the prevalence of the above mentioned metabolic disorders in renal transplant recipients, to analyze the impact of immunosuppressive therapy on the manifestation of these mentioned metabolic disorders, and to analyze the antihypertensive therapy applied. We analyzed 53 patients that underwent renal transplantation at Rijeka University Hospital Center during a two-year follow-up. Glomerulonephritis was the primary kidney disease in 14 (29.6%), polycystic kidney disease in 10 (18.87%), interstitial nephritis in 7 (13.21%), nephroangiosclerosis in 5 (18.5%), diabetic nephropathy in 4 (7.55%) and other diseases in 13 (24.53%) patients. The study included 53 patients (58.5% male), mean age 49.8 +/- 11.3 (range 27-72) years and mean dialysis treatment before transplantation 56.0 +/- 41.9 months. All patients received triple immunosuppressive therapy including a calcineurin inhibitor/MMF/corticosteroids and induction with IL-2 receptor blocker (daclizumab or basiliximab). Thirty-three (62%) patients were treated with tacrolimus and 20 (38%) with cyclosporine. The mean creatinine value was 144.92 +/- 46.49. Eighteen (34%) patients had creatinine lower than 120 mmol/L and 35 (66%) patients had a level higher than 120 mmol/L. After transplantation, 49 (92.5%) patients were treated for arterial hypertension (arterial hypertension was defined as systolic blood pressure greater than 140 mm Hg and diastolic pressure greater than 90 mm Hg or the routine use of antihypertensive therapy). Patients receiving cyclosporine had a significantly higher incidence of arterial hypertension as compared with patients on tacrolimus (P=0.025). Among patients with serum creatinine level higher than 120 mmol/L, 32 (65.3%) patients had hypertension, 9 (17%) achieved target blood pressure (<130/80 mm Hg), 8 (16.32%) were treated with one drug, 24 (48.98%) with two drugs, 15 (30.61%) with three drugs and 2 (4.09%) with more than three antihypertensives. Only four patients did not take any antihypertensive medication. The most often used antihypertensive drugs were calcium channel blockers (40.4% of patients), beta-blockers (26.6%), and RAS inhibitors (9.2% of patients received ACE inhibitors and 16.5% ARB). In 6 (11.3%) patients, posttransplant diabetes mellitus developed and 21 (39.62%) patients were treated for metabolic lipid disorder. In order to identify patients at a higher risk of developing cardiovascular disease with time, it is essential that kidney transplant recipients undergo regular follow up of graft function, blood pressure, and metabolic parameters. Good graft function is important to improve the quality of life and decrease mortality of renal transplant recipients.