Scanning of 16S Ribosomal RNA for Peptide Nucleic Acid Targets.
We have designed a protocol and server to aid in the search for putative binding sites in 16S rRNA that could be targeted by peptide nucleic acid oligomers. Various features of 16S rRNA were considered to score its regions as potential targets for sequence-specific binding that could result in inhibition of ribosome function. Specifically, apart from the functional importance of a particular rRNA region, we calculated its accessibility, flexibility, energetics of strand invasion by an oligomer, as well as similarity to human rRNA. To determine 16S rRNA flexibility in the ribosome context, we performed all-atom molecular dynamics simulations of the 30S subunit in explicit solvent. We proposed a few 16S RNA target sites, and one of them was tested experimentally to verify inhibition of bacterial growth by a peptide nucleic acid oligomer.


Examining vaccination coverage in Germany: spatiotemporal clustering of MMR coverage, 2008-14.
Vaccine hesitancy is an increasing global health threat but much of the recent research has centred on the USA. European countries provide an interesting context due to increases in vaccine-preventable disease outbreaks as well as variability in vaccination laws. We investigated the spatiotemporal clustering of Measles, Mumps, and Rubella vaccination coverage in Germany, a country with a historic absence of compulsory vaccination laws. We also examined measles incidence in the context of the spatiotemporal clustering results. While we did not identify strong spatial patterns of geographic clustering in Germany, our results suggest a potential relationship between measles incidence and vaccination coverage cluster status.


Alcohol and pregnancy: doctors' attitudes, knowledge and clinical practice.
This study was undertaken to gain an understanding about doctors' perspectives on alcohol consumption in pregnancy. The specific aim was to examine attitudes, knowledge and clinical practice of a sample of New Zealand doctors. A questionnaire was sent to all paediatricians, all obstetricians and a random sample of general practitioners throughout New Zealand. All respondents felt there should be a limit on alcohol consumption in pregnancy and 46% recommended abstinence. Doctors perceived public awareness of the risks of alcohol consumption in pregnancy to be poor and over 90% believed awareness needed to improve. Eighty-nine per cent of obstetricians and 84% of general practitioners reported they felt sufficiently knowledgeable to inform people of the risks of alcohol consumption in pregnancy. Fifty-nine per cent of obstetricians and 40% of general practitioners routinely enquire about alcohol consumption at the first antenatal contact (p < 0.003). Fifty three per cent of obstetricians and 48% of general practitioners routinely advise women about alcohol consumption at the first antenatal contact. Doctors in New Zealand believe alcohol in pregnancy is an important health issue. Awareness of the risks of alcohol consumption in pregnancy is perceived as poor. Doctors' attitudes to alcohol consumption in pregnancy do not reflect their reported clinical practice.


The mechanistic action of carbon dioxide on a neural circuit and NMJ communication.
Previous studies examining behavioral responses to CO(2) revealed that high [CO(2)] acts as a natural repellent in a concentration dependent manner for crayfish. Physiologically, CO(2) can rapidly block the autonomic responses in heart rate, as well as, inhibit an escape tail flip reflex in crayfish. Here, we demonstrate that the behavioral observations can be mechanistically explained by CO(2) blocking glutamate receptors at the neuromuscular junction and through inhibition of recruiting motor neurons within the CNS. The effects are not mimicked with a lower pH in the bathing solution. Since spontaneous and sensory-evoked activities in the sensory root and motor neurons are reduced by CO(2), this is an anesthetic effect. We propose this is due to blockage of electrical synapses, as well as, some of the central glutamatergic-drive. We used agonists and antagonists (glutamate, nicotine, domoic acid, cadmium, heptanol) to various synaptic inputs, which are possibly present in the ventral nerve cord (VNC). Results from these chemicals supported the idea that there is electrical as well as chemical drive within the circuit that can modulate intrinsic as well as sensory evoked activity in the motor neurons. We have documented that CO(2) has actions in the periphery as well as in the CNS, to account for the behavioral responses previously shown. Furthermore, we document that gap junctions as well as glutamatergic synapses are potential targets. This study also aids in the dissection of a neural circuitry within the VNC that drives spontaneous and sensory evoked activity of the superficial flexor motor neurons.


Active Observation as an Alternative to Invasive Treatments for Pediatric Head and Neck Lymphatic Malformations.
An increasing number of treatment modalities for lymphatic malformations are being described, complicating therapeutic decisions. Understanding lymphatic malformation natural history is essential. We describe management of head and neck lymphatic malformations where decisions primarily addressed lesion-induced functional compromise (ie, breathing, swallowing) to identify factors associated with invasive treatment and active observation. We hypothesize that non-function threatening malformations can be observed. Retrospective case series. Retrospective case series of consecutive head and neck lymphatic malformation patients (2000-2017) with over 2 years of follow-up. Patient characteristics were summarized and associations with invasive treatment (surgery or sclerotherapy) tested using Fisher's exact. In observed patients, factors associated with spontaneous regression were assessed with Fisher's exact test. Of 191 patients, 101 (53%) were male, 97 (51%) Caucasian, and 98 (51.3%) younger than 3 months. Malformations were de Serres I-III 167 (87%), or IV-V 24 (12%), and commonly located in the neck (101, 53%), or oral cavity (36, 19%). Initial treatments included observation (65, 34%) or invasive treatments such as primary surgery (80, 42%), staged surgery (25, 13%), or primary sclerotherapy (9, 5%). Of 65 initially observed malformations, 8 (12%) subsequently had invasive treatment, 36 (58%) had spontaneous regression, and 21 (32%) elected for no invasive therapy. Spontaneous regression was associated with location in the lateral neck (P = .003) and macrocystic malformations (P = .017). Head and neck lymphatic malformation treatment selection can be individualized after stratifying by stage, presence of functional compromise, and consideration of natural history. Recognizing the spectrum of severity is essential in evaluating efficacy of emerging treatments, as selected malformations may respond to observation. 4 Laryngoscope, 131:1392-1397, 2021.


The cost of transcatheter aortic valve implantation according to different access routes.
Identifying the average direct cost of TAVI (Transcatheter Aortic Valve Implantation) for the different access routes. This is a research with a quantitative, exploratory and descriptive approach carried out in a government teaching hospital in the state of São Paulo. The average direct cost of TAVI procedures by the access routes resulted in R$82,826.38 (transfemoral route), R$79,440.91 (transaortic route) and R$78,173.41 (transapical route). The transcatheter valve cost represented a percentage variation between 78.47% and 83.14% of the total cost of the procedure. The Kruskal-Wallis test was used and presented a statistically significant difference between the three access routes: p=0.008. The Bonferroni test showed a difference in the association between transfemoral and transapical routes, while no statistically significant difference was observed in association with the transaortic route. The results are important for formulating adequate funding policies for the hospital network and understanding the costs according to the route facilitates rationalizing resources in order for them to be guaranteed for patients who present surgical contraindication to the valve implant.


Development of plasmid DNA reference material for the quantification of genetically modified common bean embrapa 5.1.
The genetically modified (GM) common bean Embrapa 5.1 was recently approved for commercialization. The reliable detection and quantification of GM organisms is strongly dependent on validated methods as well as calibration systems. This work presents the development of a calibrant plasmid for Embrapa 5.1 common bean detection. The reaction parameters were determined and compared for both the plasmid DNA (pDNA) and the genomic DNA (gDNA). PCR efficiencies for pDNA were 81% for the construction-specific assays and 76% for the taxon-specific assay, whereas for gDNA efficiencies were 94 and 93%, respectively. The limits of detection (LOD) in both qPCR assays were 10(2) and 10(3) copies of gDNA and pDNA per PCR reaction, respectively. This is sufficient to detect 0.067 and 0.67% of GM common bean in 100 ng of DNA, respectively, which is in agreement with detecting the 1% GM content required by the Brazilian legislation.


Phloem Unloading of Amino Acids at the Site of Attachment of Cuscuta europaea.
By washing out (14)C-solutes or (3)H-solutes in 0.5 mm CaSO(4) during a period of 5 to 6 hours, the release of amino acids by excised stem segments of broad bean (Vicia faba L. cv Witkiem) was studied. Three hours after pulse labeling with l-valine, l-asparagine, or alpha-aminoisobutyric acid (AIB), hollow stem segments were excised from the plant and incubated in a washout solution.In experiments with valine and asparagine, stem segments parasitized by Cuscuta europaea released a higher percentage of labeled solutes into the bathing medium than control segments. This can be ascribed to enhanced phloem unloading at the site of attachment of Cuscuta. At low temperature (0 degrees C) and after addition of p-chloromercuribenzene sulfonate to the bathing medium, parasitized segments did not release an enhanced percentage of labeled solutes, in comparison with control segments. These data suggest a metabolic control of the phenomenon of enhanced phloem unloading of amino acids. In experiments with AIB, an enhanced release of labeled solutes could not clearly be observed, but at the site of attachment of Cuscuta an accumulation of labeled solutes was measured. Accumulation of AIB in parenchyma cells, before the start of a washout experiment, will tend to obscure the phenomenon of enhanced phloem unloading.


Evaluation and development of spinosyns to control ectoparasites on cattle and sheep.
The spinosyns are a novel family of fermentation-derived natural products that exhibit potent insecticidal activities. Spinosad, a naturally-occurring mixture of spinosyn A and spinosyn D, has successfully established its utility for crop protective applications in the agrochemical field. Potential applications of this unique chemical family of macrolides also have been investigated in the field of animal health. Applications for the control of blowfly strike and lice on sheep have now been commercially developed and registered in Australia and potential applications for the control of ectoparasites on cattle are being studied.


[Current Issue of Information Management about Pharmaceutical and Medical Device Interaction in Hospital].
Contact between plastic medical devices and medicine causes damage to the medical device and liquid medicine leakage because of physicochemical reactions. These phenomena are listed as contraindications and precautions on individual package inserts of medical devices and drugs; medical device package inserts draw attention to such as interactions. We carried out a questionnaire survey of medical-, drug-, and device-safety managers in hospitals that examined the management system for medical device package inserts, responsibility for dealing with the occurrence of drug and medical device interactions, and at desirable system to avoid such occurrence. Drug package inserts are managed by pharmacists. The medical device package inserts are managed mainly by the device safety managers, as well as by other personnel, including the clinical engineer, doctor, nurse, and clinical radiographer. The survey confirmed that interactions occurred at many phenomena; the procedure involved detailing such occurrences by various medical staff to a medical-safety manager in an incident report. Our study revealed that there were many problems with the package inserts management system for medical devices. Cooperation between safety managers within hospitals is necessary to avoid such incidents.


Human rights in health systems frameworks: what is there, what is missing and why does it matter?
Global initiatives and recent G8 commitments to health systems strengthening have brought increased attention to factors affecting health system performance. While equity concerns and human rights language appear often in the global health discourse, their inclusion in health systems efforts beyond rhetorical pronouncements is limited. Building on recent work assessing the extent to which features compatible with the right to health are incorporated into national health systems, we examine how health systems frameworks have thus far integrated human rights concepts and human rights-based approaches to health in their conceptualisation. Findings point to the potential value of the inclusion of human rights in these articulations to increase the participation or involvement of clients in health systems, to broaden the concept of equity, to bring attention to laws and policies beyond regulation and to strengthen accountability mechanisms.


P2X7 receptors activate protein kinase D and p42/p44 mitogen-activated protein kinase (MAPK) downstream of protein kinase C.
Protein kinase D (PKD), also called protein kinase Cmu (PKCmu), is a serine/threonine kinase that has unique enzymic and structural properties distinct from members of the PKC family of proteins. In freshly isolated rat parotid acinar salivary cells, extracellular ATP rapidly increased the activity and phosphorylation of PKD. The stimulation by ATP required high concentrations, was mimicked by the P2X(7) receptor ligand BzATP [2'- and 3'-O-(4-benzoylbenzoyl)ATP], and was blocked by Mg(2+) and 4,4'-di-isothiocyano-2,2'-stilbene disulphonate (DIDS), suggesting that activation of PKD was mediated by P2X(7) receptors, which are ligand-gated non-selective cation channels. Phorbol ester (PMA) and the activation of muscarinic and substance P receptors also increased PKD activity. PKC inhibitors blocked ligand-dependent PKD activation and phosphorylation, determined by in vitro phosphorylation studies and by phospho-specific antibodies to two activation loop sites (Ser(744) and Ser(748)) and an autophosphorylation site (Ser(916)). ATP and BzATP also increased the tyrosine phosphorylation and activity of PKCdelta, and these stimuli also increased extracellular signal-regulated protein kinase (ERK) 1/2 activity in a PKC-dependent manner. PKD activation was not promoted by pervanadate (an inhibitor of tyrosine phosphatases) and was not blocked by PP1 (an inhibitor of Src family kinases) or genistein (a tyrosine kinase inhibitor), suggesting that tyrosine kinases and phosphatases did not play a major role in PKD activation. P2X(7) receptor-mediated signalling events were not dependent on Ca(2+) entry. These studies indicate that PKC is involved in cellular signalling initiated by P2X(7) receptors as well as by G-protein-coupled receptors, and demonstrate that PKD and ERK1/2 are activated in similar PKC-dependent signalling pathways initiated by these diverse receptor types.


Postoperative voiding interval and duration of analgesia following peripheral or caudal nerve blocks in children.
We studied the time to postoperative micturition and the duration of analgesia in 82 children aged 6 mo to 10 yr undergoing herniorrhaphy or orchiopexy under general anesthesia with N2O and halothane. All received D5 lactate Ringer's solution equivalent to 6 h maintenance intraoperatively, and oral fluids postoperatively ad libitum. At the end of surgery, patients were randomly assigned to receive one of three regional anesthetic injections using 0.25% bupivacaine: caudal, 0.75 mL/kg (group I); caudal with 1:200,000 epinephrine, 0.75 mL/kg (group II); or ilioinguinaliliohypogastric nerve block with epinephrine through the wound by the surgeon (group III). Postoperatively, blinded observers scored pain at 30 min, hourly until discharge, and by telephone at 24-36 h. In the 74 patients with successful blocks (mean age 2.5 +/- 2.4 yr), the times to micturition (group I, 202 +/- 130 min; group II, 262 +/- 164 min; group III, 196 +/- 101 min) did not differ significantly among groups. Seven patients who took more than 8 h to void required no intervention. There was no difference in the numbers without pain for > or = 4 h (74%, 64%, and 69% of groups I, II, and III), or those requiring analgesics by 24 h (66% overall). The time to postoperative voiding in children is variable and not prolonged by caudal analgesia; caudal bupivacaine with or without epinephrine and ilioinguinaliliohypogastric nerve block are equally effective for postoperative analgesia.


Maternal sensitivity moderates the impact of prenatal anxiety disorder on infant mental development.
Animal studies have shown that postnatal rearing style can modify the association between prenatal stress exposure and offspring neurodevelopmental outcomes. However, little is known about how parenting quality impacts the association between maternal prenatal anxiety and development in human infants. This prospective study examined the impact of maternal prenatal anxiety disorder and maternal caregiving sensitivity on cognitive and psychomotor development in healthy, full-term, 7-month-old infants. Women completed a clinical interview during the third trimester of pregnancy to assess anxiety symptoms meeting DSM-IV diagnostic criteria. At infant age 7 months, maternal sensitivity to infant distress and non-distress were observed and coded during the still-face procedure. Maternal postnatal (concurrent) anxiety and depression were also assessed at this time. Infant mental and psychomotor development was assessed at infant age 7 months using the Bayley Scales of Infant Development II. Analyses were based on 77 mother-infant dyads. Maternal sensitivity to infant distress moderated the association between maternal prenatal anxiety disorder and infant mental development, F (1, 77)=5.70, p=.02. Whereas there was a significant positive association between sensitivity and mental development among infants whose mothers were anxious during pregnancy, sensitivity had little impact on mental development among infants of control (non-anxious) women. Results were independent of prenatal depression and postnatal anxiety and depression. A caregiving moderation effect was not found for infant psychomotor development, p>.10. These findings are consistent with a cumulative risk model suggesting that maternal prenatal anxiety and quality of maternal care act in concert to shape infant outcomes.


Assessment of oral mucosal lesions among psychiatric inmates residing in central jail, Bhopal, Madhya Pradesh, India: A cross-sectional survey.
The aim of the current cross-sectional study was to assess oral mucosal lesions among psychiatric jail patients residing in central jail, Bhopal, Madhya Pradesh, India. The study subjects consisted of prediagnosed psychiatric patients residing in central jail, Bhopal. A matched control consisting of cross section of the population, that is, jail inmates residing in the same central jail locality was also examined to compare the psychiatric subjects. The WHO oral health assessment proforma, 1997 along with 18-item questionnaire was used for the oral health examination. A total number of subjects examined were 244, which comprised of 122 psychiatric inmates and 122 nonpsychiatric inmates. Among all psychiatric inmates, about 57.4% of inmates had a diagnosis of depression, 14.8% had psychotic disorders (like schizophrenia), and 12.3% had anxiety disorder. A total of 77% study inmates, which comprised of 87.7% psychiatrics and 66.4% nonpsychiatrics had a habit of tobacco consumption (smokeless or smoking). Overall prevalence of oral mucosal lesions among the inmates was 85 (34.8%), which comprised of 39.3% psychiatric inmates and 30.3% nonpsychiatric inmates. The information presented in this study adds to our understanding of the common oral mucosal lesions occurring in a psychiatric inmate population. Leukoplakia and oral submucous fibrosis were the most common types of oral mucosal lesions found. Efforts to increase patient awareness of the oral effects of tobacco use and to eliminate the habit are needed to improve oral and general health of the prison population.


In vitro fertilization of in vitro matured oocytes obtained from the follicles without hCG exposure for prevention of severe ovarian hyperstimulation syndrome: a case report.
We aspirated ovarian follicles of an infertile patient who encountered a great risk of ovarian hyperstimulation (OHSS) during her ovulation-induction cycle, which had been stimulated with gonadotropins, in order to avoid OHSS without interrupting the treatment. If this action were to yield a considerable number of immature oocytes, some of which were to achieve in vitro maturation and subsequent fertilization, this method could be an alternative to conventional ovulation-induction methods for patients who repeatedly present imminent signs of hyperstimulation. However, the number of oocytes collected from the patient was disappointingly low, even though a large number of follicles were thoroughly aspirated. One of these oocytes was matured in vitro in a medium containing 30% follicular fluid and granulosa cells of mature follicles, fertilized, cryopreserved, and transferred in a later artificial cycle; but pregnancy was not achieved. A low number of recovered oocytes from patients in this situation might be a factor that greatly limits the clinical applications of this method.


Analysis of gun phenotype in barley magnesium chelatase and Mg-protoporphyrin IX monomethyl ester cyclase mutants.
The ability of barley (Hordeum vulgare L.) chlorophyll biosynthetic mutants to regulate the expression of Lhc genes was analyzed by a microarray approach. The Lhc genes are located in the nucleus and encode chlorophyll a/b binding proteins of the light-harvesting complex. The chlorophyll a/b binding proteins are some of the many proteins, which are imported to the chloroplast. It has been suggested that the chloroplast can regulate expression of nuclear genes encoding chloroplast proteins, using a chlorophyll biosynthetic intermediate such as Mg-protoporphyrin IX (MP) or Mg-protoporphyrin IX monomethyl ester (MPE) as a signal molecule. These compounds are intermediates between the two enzymes magnesium-chelatase (EC 22.214.171.124) and Mg-protoporphyrin IX monomethyl ester cyclase (EC 18.104.22.168) in the chlorophyll biosynthetic pathway. Genomes uncoupled (gun) mutants are defective in the chloroplast-to-nucleus signal transduction and express Lhc even when chloroplast development is inhibited by the herbicide norflurazon. We show that barley xantha-f, -g and -h mutants, defective in the three Mg-chelatase genes, have a gun phenotype. In contrast, a xantha-l mutant, defective in a gene of Mg-protoporphyrin monomethyl ester cyclase did not. Genome uncoupling in the xantha-f, -g, -h and -l mutants was also analyzed in absence of norflurazon. All mutants showed transcription of Lhc. This was unexpected in the case of xantha-l as this mutant showed accumulation of MPE, which has been suggested to be one of the two negative regulators of Lhc transcription. We suggest that chlorophyll intermediates may only function as signal molecules at an early developmental stage of chloroplast development.


Spy&Go purification of SpyTag-proteins using pseudo-SpyCatcher to access an oligomerization toolbox.
Peptide tags are a key resource, introducing minimal change while enabling a consistent process to purify diverse proteins. However, peptide tags often provide minimal benefit post-purification. We previously designed SpyTag, forming an irreversible bond with its protein partner SpyCatcher. SpyTag provides an easy route to anchor, bridge or multimerize proteins. Here we establish Spy&Go, enabling protein purification using SpyTag. Through rational engineering we generated SpyDock, which captures SpyTag-fusions and allows efficient elution. Spy&Go enabled sensitive purification of SpyTag-fusions from Escherichia coli, giving superior purity than His-tag/nickel-nitrilotriacetic acid. Spy&Go allowed purification of mammalian-expressed, N-terminal, C-terminal or internal SpyTag. As an oligomerization toolbox, we established a panel of SpyCatcher-linked coiled coils, so SpyTag-fusions can be dimerized, trimerized, tetramerized, pentamerized, hexamerized or heptamerized. Assembling oligomers for Death Receptor 5 stimulation, we probed multivalency effects on cancer cell death. Spy&Go, combined with simple oligomerization, should have broad application for exploring multivalency in signaling.


Evolution of the head-trunk interface in tetrapod vertebrates.
Vertebrate neck musculature spans the transition zone between head and trunk. The extent to which the cucullaris muscle is a cranial muscle allied with the gill levators of anamniotes or is instead a trunk muscle is an ongoing debate. Novel computed tomography datasets reveal broad conservation of the cucullaris in gnathostomes, including coelacanth and caecilian, two sarcopterygians previously thought to lack it. In chicken, lateral plate mesoderm (LPM) adjacent to occipital somites is a recently identified embryonic source of cervical musculature. We fate-map this mesoderm in the axolotl (Ambystoma mexicanum), which retains external gills, and demonstrate its contribution to posterior gill-levator muscles and the cucullaris. Accordingly, LPM adjacent to the occipital somites should be regarded as posterior cranial mesoderm. The axial position of the head-trunk border in axolotl is congruent between LPM and somitic mesoderm, unlike in chicken and possibly other amniotes.


[Nursing interventions for the most frequent complications during hemodialysis procedure: literature review].
Hemodialysis procedure has potential complications and nurses must be able to intervent on them. Considering this context, this article aims to describe the most frequent hemodialysis-related complications as well as nursing-related interventions. This bibliographic review consists in LILACS, BDENF and MEDLINE search using pertinent descriptors. Results demonstrated that major complications are: hypotension, hypertension, cramps, nausea and vomiting, headache, chest and low back pain, scratching, fever and shriving. For these complications there are specific nursing interventions that can be delivered. It was concluded that nurse's role is essential for monitoring, identification, and intervention in such complications and that this role also is a differential to obtain quality in hemodialysis procedure. However, there is a need to perform more research in nursing area to better define the nurse's role.


[Koro-like symptoms in a recurrent depressive disorder].
We report the case of a German male with a major depressive episode who also suffered from the terrifying perception that his penis was shrinking. These so-called koro-like symptoms (KLS) had also been present in earlier depressive episodes and subsided in the symptom-free interval of the recurrent depressive disorder. Under sufficient antidepressant medication with venlafaxine and lithium not only KLS but also the depressive symptoms remitted. The course of illness provides further evidence that KLS are not a distinct clinical entity in Western countries, but represent a concomitant syndrome that requires treatment of the underlying illness.


Animal Models of CMT2A: State-of-art and Therapeutic Implications.
Charcot-Marie-Tooth disease type 2A (CMT2A), arising from mitofusin 2 (MFN2) gene mutations, is the most common inherited axonal neuropathy affecting motor and sensory neurons. The cellular and molecular mechanisms by which MFN2 mutations determine neuronal degeneration are largely unclear. No effective treatment exists for CMT2A, which has a high degree of genetic/phenotypic heterogeneity. The identification of mutations in MFN2 has allowed the generation of diverse transgenic animal models, but to date, their ability to recapitulate the CMT2A phenotype is limited, precluding elucidation of its pathogenesis and discovery of therapeutic strategies. This review will critically present recent progress in in vivo CMT2A disease modeling, discoveries, drawbacks and limitations, current challenges, and key reflections to advance the field towards developing effective therapies for these patients.


A pilot randomized trial comparing CD34-selected versus unmanipulated hemopoietic stem cell transplantation for severe, refractory rheumatoid arthritis.
Evidence from animal studies, case reports, and phase I studies suggests that hemopoietic stem cell transplantation (HSCT) can be effective in the treatment of rheumatoid arthritis (RA). It is unclear, however, if depletion of T cells in the stem cell product infused after high-dose chemotherapy is beneficial in prolonging responses by reducing the number of infused autoreactive T cells. This pilot multicenter, randomized trial was undertaken to obtain feasibility data on whether CD34 selection (as a form of T cell depletion) of an autologous stem cell graft is of benefit in the HSCT procedure in patients with severe, refractory RA. Thirty-three patients with severe RA who had been treated unsuccessfully with methotrexate and at least 1 other disease-modifying agent were enrolled in the trial. The patients received high-dose immunosuppressive treatment with 200 mg/kg cyclophosphamide followed by an infusion of autologous stem cells that were CD34 selected or unmanipulated. Safety, efficacy (based on American College of Rheumatology [ACR] response criteria), and time to recurrence of disease were assessed on a monthly basis for up to 12 months. All patients were living at the end of the study, with no major unexpected toxicities. Overall, on an intent-to-treat basis, ACR 20% response (ACR20) was achieved in 70% of the patients. An ACR70 response was attained in 27.7% of the 18 patients who had received CD34-selected cells and 53.3% of the 15 who had received unmanipulated cells (P = 0.20). The median time to disease recurrence was 147 days in the CD34-selected cell group and 201 days in the unmanipulated cell group (P = 0.28). There was no relationship between CD4 lymphopenia and response, but 72% of rheumatoid factor (RF)-positive patients had an increase in RF titer prior to recurrence of disease. HSCT can be performed safely in patients with RA, and initial results indicate significant responses in patients with severe, treatment-resistant disease. Similar outcomes were observed in patients undergoing HSCT with unmanipulated cells and those receiving CD34-selected cells. Larger studies are needed to confirm these findings.


The effects of prostacyclin on canine hepatic bile flow.
The effect of prostacyclin on canine hepatic bile flow was evaluated. Utilizing chronic, unanesthetized bile fistula dogs, prostacyclin was found to significantly increase bile flow rates and bile bicarbonate and cyclic AMP concentration and output when compared to control values. The choleretic response was not due to the effect of the principal metabolic endproduct of prostacyclin, 6-keto-PGF1 alpha, as this substance increased bile flow but did not increase bicarbonate or cyclic AMP concentrations in bile. Prostacyclin did not increase [14C]erythritol clearance in bile suggesting that it stimulates bile duct secretion rather than the bile salt-independent fraction of canalicular bile. To ascertain if a relationship exists between the bicarbonate-rich choleresis produced by prostacyclin and that produced by secretin, the effects of prostacyclin and indomethacin on the choleresis produced by endogenous secretin stimulation were evaluated. During intraduodenal acid infusion, prostacyclin significantly increased bile flow. The increase was not secondary to increased secretin release as plasma secretin levels were not significantly changed from control levels. Prostaglandin synthetase inhibition by indomethacin administration did not alter the choleresis produced by intraduodenal acid. The prostacyclin-induced changes in bile flow were further evaluated in acute experiments in anesthetized dogs during which the effects of prostacyclin on systemic blood pressure, hepatic blood flow and cyclic AMP metabolism could be simultaneously determined. The choleresis produced by prostacyclin occurred in the presence of decreased systemic arterial blood pressure and hepatic blood flow. The increased bile cyclic AMP secretion produced by prostacyclin was not associated with increases in systemic or hepatogenous cyclic AMP. Prostacyclin increases canine bile flow and bicarbonate secretion, a process which may be mediated by cyclic AMP. The choleresis is not secondary to changes in hepatic blood flow or secretin release.


Long-Term Survival of Patients with Metastatic Non-Small-Cell Lung Cancer over Five Decades.
Novel therapeutics and supportive care improved outcomes for metastatic non-small-cell lung cancer (mNSCLC) patients. Major advances over the past five decades include the introduction of combination chemotherapy, small molecules targeting mutant proteins, especially EGFR, and more recently immunotherapy. We aim to document real-world long-term survival over the past five decades. Survival statistics were extracted from the Survival, Epidemiology, and End Results (SEER) database for mNSCLC patients during 1973-2015. Two- and five-year survival (2yS and 5yS) were analyzed using Kaplan-Meier and proportional hazard models. The study population consisted of 280,655mNSCLC patients diagnosed during 1973-2015. Longer survival was seen in younger, female, married, Asian/Pacific Islander race, adenocarcinoma, lower grade, more recent diagnosis, higher income, and chemotherapy-treated patients. 2yS increased during the study period from 2.6% to 12.9%, and 5yS increased from 0.7% to 3.2%. 2yS of patients <50 years of age rose from 2.1% to 22.8%, and their 5yS rose from 0.7% to 6.2%. 2yS of adenocarcinoma patients improved from 2.7% to 16.2%, and their improved 5yS from 1.1% to 3.9%. Between 1973 and 2015, there was a dramatic improvement in long-term survival, with an approximately five-fold increase in both 2yS and 5yS. Nonetheless, absolute numbers of long-term survivors remained low, with less than 4% living 5 years. This provides a baseline to compare long-term outcomes seen in the current generation of clinical trials.


Soybean-Oil Lipid Minimization for Prevention of Intestinal Failure-Associated Liver Disease in Late-Preterm and Term Infants With Gastrointestinal Surgical Disorders.
Intestinal failure-associated liver disease (IFALD), a multifactorial disease, is common among infants with gastrointestinal surgical disorders (GISDs). Prolonged soy-based intravenous lipid emulsion (S-ILE) intake is associated with IFALD, but preventive studies of limiting S-ILE have been inconclusive. Furthermore, a double-blind, randomized preventive trial (DBRPT) of S-ILE intake has not been performed in infants with GISDs. Our objective was to compare the effect of 1 g/kg/d vs 2 g/kg/d S-ILE intake for 6 weeks on the incidence of IFALD and the rate of rise of direct bilirubin (DB) in infants with GISDs. A DBRPT was conducted in infants with GISDs at ≥34 weeks' gestational age (GA) admitted to the NICU within 72 hours after birth. Infants were randomized in a 1:1 ratio to receive either 1 or 2 g/kg/d S-ILE for 6 weeks. IFALD was defined as DB ≥2 mg/dL. Forty infants were studied. The 2 groups had similar clinical characteristics except for GA and blood group incompatibility. Thirty percent of infants in each group developed IFALD (P = .94). However, infants in the group receiving 1 g/kg/d S-ILE (n = 20) had a lower rate of rise of DB compared with infants in the group receiving 2 g/kg/d S-ILE (n = 20). Reducing S-ILE intake for 6 weeks in infants with GISD at ≥34 weeks' GA may not prevent IFALD. The extrapolated data on the rate of rise of DB suggest a possible risk of earlier development of IFALD with S-ILE intake of 2 g/kg/d, as compared with 1 g/kg/d, beyond the 6-week study period.


Characteristics of the memory sources of dreams: A new version of the content-matching paradigm to take mundane and remote memories into account.
Several studies have demonstrated that dream content is related to the waking life of the dreamer. However, the characteristics of the memory sources incorporated into dreams are still unclear. We designed a new protocol to investigate remote memories and memories of trivial experiences, both relatively unexplored in dream content until now. Upon awakening, for 7 days, participants identified the waking life elements (WLEs) related to their dream content and characterized them and their dream content on several scales to assess notably emotional valence. Thanks to this procedure, they could report WLEs from the whole lifespan, and mundane ones before they had been forgotten. Participants (N = 40, 14 males, age = 25.2 ± 7.6) reported 6.2 ± 2.0 dreams on average. For each participant, 83.4% ± 17.8 of the dream reports were related to one or more WLEs. Among all the WLEs incorporated into dreams dated by the participants (79.3 ± 19%), 40.2 ± 30% happened the day before the dream, 26.1 ± 26% the month before (the day before excluded), 15.8 ± 21% the year before the dream (the month before excluded), and 17.9 ± 24% happened more than one year before the dream. As could be expected from previous studies, the majority of the WLEs incorporated into dreams were scored as important by the dreamers. However, this was not true for incorporated WLEs dating from the day before the dream. In agreement with Freud's observations, the majority of the day residues were scored as mundane. Finally, for both positive and negative WLEs incorporated into dreams, the dreamt version of the WLE was rated as emotionally less intense than the original WLE. This result, showing that dreams tend to attenuate the emotional tone of waking-life memories towards a more neutral one, argues in favor of the emotional regulation hypothesis of dreaming.


Deferasirox: an update.
Cumulative data from prospective studies in over 3,000 patients with a range of transfusion dependent anemias have established key principles about the efficacy and safety of deferasirox (DFS). Pivotal preregistration studies established the relationship between dose, iron excretion, and tolerability using changes in liver iron concentration (LIC) to measure changes in body iron. The importance of the transfusional iron-loading rate to treatment response has been clearly demonstrated. Unwanted effects in these core studies included skin rash and gastrointestinal disturbances. Serum creatinine increments were initially seen in about one-third of patients but have not been progressive in study extensions up to 4.5 years. The proportion of patients with serum ferritin <1,000 microg/L has risen steadily without an increase in adverse events and doses >30 mg/kg/day have been given in >200 patients without an increase in adverse events. The large-scale EPIC trial involving >1,600 patients has revealed further insights about the interaction of dose with ferritin trends and safety markers. Cardiac substudies of this trial, in >100 patients with established mild to moderate myocardial iron loading by T2*, show a significant reduction in cardiac iron.


Impact of the "Sling Shot" Supportive Device on Upper-Body Neuromuscular Activity during the Bench Press Exercise.
The aim of this study was to compare the muscle activity between the sling shot assisted (SS) and control (CONT) flat barbell bench press for selected external loads of 70%, 85%, 100% one-repetition maximum (1RM). Ten resistance-trained men participated in the study (age = 22.2 ± 1.9 years, body mass = 88.7 ± 11.2 kg, body height = 179.5 ± 4.1, 1RM in the bench press = 127.25 ± 25.86 kg, and strength training experience = 6 ± 2.5 years). Evaluation of peak muscle activity of the dominant body side was carried out using surface electromyography (sEMG) recorded for the triceps brachii, pectoralis major, and anterior deltoid during each attempt. The three-way repeated measure ANOVA revealed statistically significant main interaction for condition x muscle group (p < 0.01; η2 = 0.569); load x muscle group (p < 0.01; η2 = 0.709); and condition x load (p < 0.01; η2 = 0.418). A main effect was also observed for condition (p < 0.01; η2 = 0.968); load (p < 0.01; η2 = 0.976); and muscle group (p < 0.01; η2 = 0.977). The post hoc analysis for the main effect of the condition indicated statistically significant decrease in %MVIC for the SS compared to CONT condition (74.9 vs. 88.9%MVIC; p < 0.01; ES = 0.39). The results of this study showed that using the SS significantly affects the muscle activity pattern of the flat bench press and results in its acute decrease in comparison to an equal load under CONT conditions. The SS device may be an effective tool both in rehabilitation and strength training protocols by increasing stability with a reduction of muscular activity of the prime movers.


Hand infections.
The hand is a commonly injured part of the body that frequently becomes infected. Improperly treated hand infections can lead to severe disability including stiffness, contracture, and amputation. This article describes the current concepts of diagnosis and treatment of common hand infections.


Parent perspectives of therapy services for their children with physical disabilities.
Children who have physical disabilities typically attend occupational and physical therapy services on a regular basis. The importance of being family centred when providing services to children with a disability has been highlighted in recent years. Thus, it was considered important to gather the opinions of parents towards the services their child receives. To explore the perspectives of parents of children with physical disabilities to occupational and physical therapy services provided to their child. Open interviews were conducted with 17 parents (14 mothers and three fathers) of children aged 7-13, selected through a purposeful sample. Data analysis was based on an inductive approach. Nine categories emerged and were organized under three main headings: The role of the therapist, service location and arrangements, and characteristics of good service. Although several positive remarks were made, many parents in this study were poorly informed of intervention goals and what took place during therapy sessions. Most parents wished for mutual respect, joint decision-making in planning intervention, and collaboration with the therapy services. The aspiration for active but manageable roles that did not demand a burdensome amount of the parents' time and energy was evinced. The parents became increasingly critical of the services, as their children grew older. They placed emphasis on services being offered in their local community, and that more specialized service should be centralized, especially for the children with the most complex needs. The results reflect the importance of the needs and wants of the parents and children being respected. Thus, parents should play an active role in defining priorities and strategies for implementation. The results also indicate that therapists need to put more thought into the conditions and environment of the child instead of focusing solely on underlying issues connected to their impairments.


Sequence of the genomic RNA of nudaurelia beta virus (Tetraviridae) defines a novel virus genome organization.
The monopartite genome of Nudaurelia beta virus, the type species of the Betatetravirus genus of the family Tetraviridae, consists of a single-stranded positive-sense RNA (ss+RNA) of 6625 nucleotides containing two open reading frames (ORFs). The 5' proximal ORF of 5778 nucleotides encodes a protein of 215 kDa containing three functional domains characteristic of RNA-dependent RNA polymerases of ss+RNA viruses. The 3' proximal ORF of 1836 nucleotides, which encodes the 66-kDa capsid precursor protein, overlaps the replicase gene by more than 99% (1827 nucleotides) and is in the +1 reading frame relative to the replicase reading frame. This capsid precursor is expressed via a 2656-nucleotide subgenomic RNA. The 3' terminus of the genome can be folded into a tRNA-like secondary structure that has a valine anticodon; the tRNA-like structure lacks a pseudoknot in the aminoacyl stem, a feature common to both genera of tetraviruses. Comparison of the sequences of Nudaurelia beta virus and another member of the Tetraviridae, Helicoverpa armigera stunt virus, which is in the genus Omegatetravirus, shows identities of 31.6% for the replicase and 24.5% for the capsid protein. The viruses in the genera Betatetravirus and Omegatetravirus of the Tetraviridae are clearly related but show significant differences in their genome organization. It is concluded that the ancestral virus with a bipartite genome, as found in the genus Omegatetravirus, likely evolved from a virus with an unsegmented genome, as found in the genus Betatetravirus, through evolution of the subgenomic RNA into a separate genomic component, with the accompanying loss of the capsid gene from the longer genomic RNA.


Language experience and the organization of brain activity to phonetically similar words: ERP evidence from 14- and 20-month-olds.
The ability to discriminate phonetically similar speech sounds is evident quite early in development. However, inexperienced word learners do not always use this information in processing word meanings [Stager & Werker (1997). Nature, 388, 381-382]. The present study used event-related potentials (ERPs) to examine developmental changes from 14 to 20 months in brain activity important in processing phonetic detail in the context of meaningful words. ERPs were compared to three types of words: words whose meanings were known by the child (e.g., ''bear''), nonsense words that differed by an initial phoneme (e.g., ''gare''), and nonsense words that differed from the known words by more than one phoneme (e.g., ''kobe''). These results supported the behavioral findings suggesting that inexperienced word learners do not use information about phonetic detail when processing word meanings. For the 14-month-olds, ERPs to known words (e.g., ''bear'') differed from ERPs to phonetically dissimilar nonsense words (e.g., ''kobe''), but did not differ from ERPs to phonetically similar nonsense words (e.g., ''gare''), suggesting that known words and similar mispronunciations were processed as the same word. In contrast, for experienced word learners (i. e., 20-month-olds), ERPs to known words (e.g., ''bear'') differed from those to both types of nonsense words (''gare'' and ''kobe''). Changes in the lateral distribution of ERP differences to known and unknown (nonce) words between 14 and 20 months replicated previous findings. The findings suggested that vocabulary development is an important factor in the organization of neural systems linked to processing phonetic detail within the context of word comprehension.


Relationship between the Subunits of Leucoplast Pyruvate Kinase from Ricinus communis and a Comparison with the Enzyme from Other Sources.
Two cDNA clones, PK(p)alpha and PK(p)beta, for the leucoplast isozyme of pyruvate kinase have been isolated and characterized. A Southern blot of castor (Ricinus communis) DNA probed with PK(p)alpha indicates the presence of a single gene for PK(p). Most (1610 base pairs) of the sequence of both cDNAs is identical. These 1610 base pairs begin with an ATG translation initiation codon, and have 248 base pairs of 3'-untranslated and 1362 base pairs of coding sequence. The sequences of the two clones 5'- to the identical regions are different but both encode peptides with a high percentage of hydrophobic amino acids. The derived sequence of PK(p)alpha encodes eight amino acid residues which have been identified as the amino-terminus of one subunit of PK(p) from castor seed leucoplasts when the enzyme is purified in the absence of cysteine endopeptidase inhibitors. The sequence upstream of these amino acids is possibly the transit peptide for this protein. When PK(p) is extracted under conditions that eliminate its proteolytic degradation, its alpha-subunit has a relative molecular weight equal to the full-length coding sequence of PK(p)alpha. The data indicate that the transit peptide for the subunit of leucoplast pyruvate kinase encoded by PK(p)alpha is not cleaved until the protein is released from the plastid. The derived amino acid sequences of PK(p)alpha and PK(p)beta are most closely related to Escherichia coli pyruvate kinase. Although the residues involved in substrate binding are conserved in leucoplast pyruvate kinase, there is no phosphorylation site and only 5 of 15 amino acids in the E. coli fructose-1,6-bisphosphate binding site are conserved.


Personalizing Treatment: Between Primary and Secondary Prevention.
Current American College of Cardiology/American Heart Association guidelines for the management of patients with elevated blood cholesterol increasingly emphasize assessment of atherosclerotic cardiovascular disease (ASCVD) risk in deciding when to initiate pharmacotherapy. The decision to treat is based primarily on mathematical integration of traditional risk factors, including age, sex, race, lipid values, systolic blood pressure, hypertension therapy, diabetes mellitus, and smoking. Advanced risk testing is selectively endorsed for patients when the decision to treat is otherwise uncertain, or more broadly interpreted as those patients who are at so-called "intermediate risk" of ASCVD events using traditional risk factors alone. These new guidelines also place new emphasis on a clinician-patient risk discussion, a process of shared decision making in which patient and physician consider the potential benefits of treatment, risk of adverse events, and patient preferences before making a final decision to initiate treatment. Advanced risk testing is likely to play an increasingly important role in this process as weaknesses in exclusive reliance on traditional risk factors are recognized, new non-statin therapies become available, and guidelines are iteratively updated. Comparative efficacy studies of the various advanced risk testing options suggest that coronary artery calcium scoring is most strongly predictive of ASCVD events. Most importantly, coronary artery calcium scoring appears to identify an important subgroup of patients with advanced subclinical atherosclerosis-who are "between" primary and secondary prevention-that might benefit from the most aggressive lipid-lowering pharmacotherapy.


Achievements in bacterial flagellar research with focus on Vibrio species.
In 1980s, the most genes involved in the bacterial flagellar function and formation had been isolated, although many of their functions or roles were not clarified. Bacterial flagella are the primary locomotive organ and are not necessary for growing in vitro but are probably essential for living in natural condition and are involved in the pathogenicity. In vitro, the flagella-deficient strains can grow at rates similar to wild-type strains. More than 50 genes are responsible for flagellar function, and the flagellum is constructed by more than 20 structural proteins. The maintenance cost of flagellum is high as several genes are required for its development. The fact that it evolved as a motor organ even with such high cost shows that the motility is indispensable to survive under the harsh environment of Earth. In this review, we focus on flagella-related research conducted by the authors for about 40 years and flagellar research focused on Vibrio spp.


The Trevo device: preclinical data of a novel stroke thrombectomy device in two different animal models of arterial thrombo-occlusive disease.
The currently available mechanical devices fail to achieve recanalization in as many as 20-40% of proximal arterial occlusion strokes. The preclinical evaluation of the safety and efficacy of a novel thrombectomy device designed to achieve immediate flow restoration by quickly removing clot is reported. Four confirmatory animal studies were performed with the Trevo device (Concentric Medical Inc, Mountain View, California, USA) in the swine (n=2) and canine (n=1) models of arterial thrombo-occlusive disease employing autologous thrombin generated thrombi. The angiographic response and the degree of device-clot incorporation were evaluated. High resolution flat panel three-dimensional CT was performed to further define the in vivo device-thrombus-vessel interaction. Finally, samples of three swine vessels treated with six passes of the device were explanted for histopathological analysis. A total of 16 clots of variable hardness and consistency were implanted in a variety of vascular settings, including the swine internal maxillary, lingual and forelimb arteries as well as the canine external carotid and vertebral arteries. Thrombolysis in Myocardial Infarction (TIMI) 2-3 reperfusion was achieved in all cases immediately after device deployment. All 16 clots were retrieved after one (n=15) or two (n=1) passes with the device. Histopathological analysis demonstrated severe disruption of the intima but no hemorrhage of media or adventitia. The experimental data suggest that the Trevo device is highly effective at achieving immediate reperfusion of occluded arteries without causing any clinically significant disruption of vascular integrity.


Anemia and blood transfusion in critically ill patients.
Anemia is a common problem in critically ill patients admitted to intensive care units (ICUs), but the consequences of anemia on morbidity and mortality in the critically ill is poorly defined. To prospectively define the incidence of anemia and use of red blood cell (RBC) transfusions in critically ill patients and to explore the potential benefits and risks associated with transfusion in the ICU. Prospective observational study conducted November 1999, with 2 components: a blood sampling study and an anemia and blood transfusion study. The blood sampling study included 1136 patients from 145 western European ICUs, and the anemia and blood transfusion study included 3534 patients from 146 western European ICUs. Patients were followed up for 28 days or until hospital discharge, interinstitutional transfer, or death. Frequency of blood drawing and associated volume of blood drawn, collected over a 24-hour period; hemoglobin levels, transfusion rate, organ dysfunction (assessed using the Sequential Organ Failure Assessment score), and mortality, collected throughout a 2-week period. The mean (SD) volume per blood draw was 10.3 (6.6) mL, with an average total volume of 41.1 (39.7) mL during the 24-hour period. There was a positive correlation between organ dysfunction and the number of blood draws (r = 0.34; P<.001) and total volume drawn (r = 0.28; P<.001). The mean hemoglobin concentration at ICU admission was 11.3 (2.3) g/dL, with 29% (963/3295) having a concentration of less than 10 g/dL. The transfusion rate during the ICU period was 37.0% (1307/3534). Older patients and those with a longer ICU length of stay were more commonly transfused. Both ICU and overall mortality rates were significantly higher in patients who had vs had not received a transfusion (ICU rates: 18.5% vs 10.1%, respectively; chi(2) = 50.1; P<.001; overall rates: 29.0% vs 14.9%, respectively; chi(2) = 88.1; P<.001). For similar degrees of organ dysfunction, patients who had a transfusion had a higher mortality rate. For matched patients in the propensity analysis, the 28-day mortality was 22.7% among patients with transfusions and 17.1% among those without (P =.02); the Kaplan-Meier log-rank test confirmed this difference. This multicenter observational study reveals the common occurrence of anemia and the large use of blood transfusion in critically ill patients. Additionally, this epidemiologic study provides evidence of an association between transfusions and diminished organ function as well as between transfusions and mortality.


[Latex allergy in patients with severe motor and intellectual disabilities syndrome].
Our experience of an anaphylactic reaction to latex in a severely disabled patient led us to investigate latex allergy in 58 cases with severe motor and intellectual disabilities syndrome. Latex specific IgE, total serum IgE, and eosinophil counts in peripheral blood were evaluated, as well as past history of treatment with medical latex materials, operation and allergic disorders. Only one case who had been operated three times, had anaphylactic reaction and mild atopic dermatitis. Fifteen cases (25.9%) had latex specific IgE of class 2 or more. In this latex positive group, past history of allergic disorders, such as bronchilal asthma, atopic dermatitis and drug eruptions, were the most prominent factor. Those without such a history were characterized by frequent use of medical latex materials and multiple operations. In conclusion, the danger of an anaphylactic reaction to latex should be recognized, particularly in the medical care for disabled patients.


Vermiculite: a review of the mineralogy and health effects of vermiculite exploitation.
Vermiculite is a mica-type mineral that is being used in increasing quantities for insulation, in composite cements, and in horticulture. No serious health risks have been found resulting from the exposure to vermiculite alone nor are any anticipated in view of its long-term chemical durability, even with respect to fibers of vermiculite. Vermiculite ores may contain a variety of other minerals including asbestos, which, if present in significant quantities, could pose a health risk to producers and end users. A variety of regulations are in place that should prevent inadvertent exposure to asbestos in vermiculites, but great care is needed if true asbestos hazards are to be correctly identified. At the same time, vermiculites containing any of a variety amphibole minerals should not be excluded from use because of mistaken identification of these minerals as asbestos. A variety of test methods that have been developed are described and recommendations are made with respect to appropriate action levels for asbestos in vermiculites or other raw materials.


Intraoperative assessment of thyroid and parathyroid lesions.
The value of intraoperative frozen section analysis of thyroid nodules and of parathyroid lesions continues to change as new and ancillary techniques (both preopearative and intraoperative) become widely used, eg, fine needle aspiration, new radiologic scan techniques, rapid hormone assays. This articles reviews the use of frozen section diagnosis in the evaluation of thyroid and parathyroid lesions, presents the current literature and the author's experiences, and proposes a practical approach to these cases.


MTSS1 hypermethylation is associated with prostate cancer progression.
This study was conducted to evaluate the influence of DNA methylation of metastasis suppressor 1 (MTSS1) on prostate cancer (PCa) progression. Forty-nine paired PCa tissue samples and normal tissue samples from The Cancer Genome Atlas were analyzed. Methylome analysis, CpG island arrays and Hierarchical clustering were used to analyze methylation profiles of PCa tissues. MTSS1 methylation level was detected by methylation-specific PCR. Relative messenger RNA and the expression level of MTSS1 protein were identified by quantitative real-time PCR (qRT-PCR) and western blot analysis. The migration, invasion, proliferation, and cell cycle were detected separately by wound-healing assay, transwell chamber assay, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay and flow cytometry. The roles of MTSS1 in PCa progression were demonstrated in vivo by tumor formation assays in nude mice. MTSS1 expression was decreased in PCa tissues in comparison with paired adjacent normal prostate tissues. Compared to the methylation of MTSS1 in normal prostate tissues based on the MethHC website, the MTSS1 in PCa tissues was hypermethylated. The expression of MTSS1 detected by qRT-PCR and western blot analysis was found to be downregulated in PCa cells and tissues. The reduced expression of MTSS1 by small interfering RNA-MTSS1 was recovered by 5-aza-2'-deoxycytidine treatment. Besides, MTSS1 demethylation inhibited migration, invasion, and proliferation of PCa cells, and induced cell cycle to be arrested at G0/G1 phase. Furthermore, it was shown by tumor xenograft assay that MTSS1 inhibited the growth of tumor in vivo. Hypermethylated MTSS1 promoted PCa cells migration, invasion, and proliferation, and suppressed cell cycle arrest at the G0/G1 phase.


Learning the Abstract General Task Structure in a Rapidly Changing Task Content.
The ability to learn abstract generalized structures of tasks is crucial for humans to adapt to changing environments and novel tasks. In a series of five experiments, we investigated this ability using a Rapid Instructed Task Learning paradigm (RITL) comprising short miniblocks, each involving two novel stimulus-response rules. Each miniblock included (a) instructions for the novel stimulus-response rules, (b) a NEXT phase involving a constant (familiar) intervening task (0-5 trials), (c) execution of the newly instructed rules (2 trials). The results show that including a NEXT phase (and hence, a prospective memory demand) led to relatively more robust abstract learning as indicated by increasingly faster responses with experiment progress. Multilevel modeling suggests that the prospective memory demand was just another aspect of the abstract task structure which has been learned.


Smoking and risk of Graves' disease.
To assess if smoking is associated with Graves' disease and, if so, to ascertain whether this association persists when controlling for confounding factors. Consecutive entry case-control study with two age- and sex-matched control subjects from two different populations per case patient. University hospital. Five groups were studied: (1) Graves' ophthalmopathy and Graves' hyperthyroidism (n = 100; divided in four subgroups according to the severity of the eye disease); (2) Graves' hyperthyroidism without clinical eye involvement (n = 100); (3) sporadic nontoxic goiter (n = 100); (4) autoimmune hypothyroidism (n = 75); and (5) toxic nodular goiter (n = 75). The study comprised 200 subjects from a hospital-based population, and 200 from a population-based group served as control subjects. Smoking status was determined from a questionnaire at the time of onset of the disease to exclude any effect of the disease itself on smoking. Smoking greatly increased the risk for Graves' ophthalmopathy (odds ratio, 7.7; 95% confidence interval, 4.3 to 13.7), but patients with Graves' hyperthyroidism alone were also more often smokers than control subjects (odds ratio, 1.9; 95% confidence interval, 1.1 to 3.2). Smoking was not associated with the other thyroid diseases studied. Essentially similar results were obtained after adjustment for differences in education between case patients and control subjects. Among the patients with Graves' ophthalmopathy, smokers had more severe eye disease than nonsmokers, but no association was found between the number of cigarettes smoked per day or the duration of smoking and the severity of the ophthalmopathy. However, there was a significant increase in the odds ratios in patients with more severe eye disease. Smoking is associated with Graves' disease, and it especially increases the risk for the development of more severe ophthalmopathy. Thus, smoking appears to be one of the multiple factors inducing Graves' disease in genetically predisposed individuals.


Molecular genetics of the Smith-Lemli-Opitz syndrome and postsqualene sterol metabolism.
The Smith-Lemli-Opitz syndrome is a disorder of morphogenesis resulting from an enzymatic defect in the last step of cholesterol metabolism (reduction of 7-dehydrocholesterol). Analysis of the defective gene and identification of mutations therein have paved the way for the study of the molecular genetics of the disorder which is caused by numerous different mutations. Future efforts should identify a postulated intracellular signalling activity of sterol intermediates, isolate proteins that govern the sterol traffic between intracellular compartments, structurally characterize the enzyme delta 7-sterol reductase defective in the Smith-Lemli-Opitz syndrome and investigate the pathomechanism of sterol depletion-induced dysmorphogenesis.


Identification of the catalytic residues of carboxylesterase from Arthrobacter globiformis by diisopropyl fluorophosphate-labeling and site-directed mutagenesis.
The role of amino acid residues in the enzymatic activity of carboxylesterase from Arthrobacter globiformis was analyzed by diisopropyl fluorophosphate (DFP) labeling and site-directed mutagenesis. The electrospray ionization mass spectrometric (ESI-MS) analysis of the esterase, covalently labeled by DFP, showed stoichiometric incorporation of the inhibitor into the enzyme. The further comparison of endopeptidase-digested fragments between native and DFP-labeled esterase by fast atom bombardment mass spectrometric (FAB-MS) analysis as well as site-directed mutagenesis indicated that Ser59 in the consensus sequence Ser-X-X-Lys, which is conserved exclusively in penicillin-binding proteins and some esterases, served as a catalytic nucleophile. In addition, the results obtained from analysis of the mutants at position 62 suggested the importance of the basic amino acid side chain at this position, and suggested the significance of this residue acting directly as a general base rather than its involvement in the maintenance of the optimum hydrogen-bonding network at the active site.


Electron Transfer in Binary Hemin-Modified Alkanethiol Self-Assembled Monolayers on Gold: Hemin's Lateral and Interfacial Interactions.
Orientated coupling of redox enzymes to electrodes by their reconstitution onto redox cofactors, such as hemin conjugated to self-assembled monolayers (SAMs) formed on the electrodes, poses the requirements for a SAM design enabling reconstitution. We show that the kinetics of electron transfer (ET) in binary SAMs of alkanethiols on gold composed of in situ hemin-conjugated 11-amino-1-undecanethiol (AUT) and diluting OH-terminated alkanethiols with 11, 6, and 2 methylene groups (MC11OH, MC6OH, and MC2OH) depends on both the SAM composition and surface density of hemin, Γheme. In AUT/MC11OH SAMs composed of equal linker/diluent lengths, the heterogeneous ET rate constant ks decreased with the Γheme and varied between 70 and 500 s-1. For shorter diluents, the ks of 245-330 s-1 (C6) and 300-340 s-1 (C2) showed a little (if any) Γheme dependence. In AUT/MC11OH SAMs, the increasing Γheme resulted in the steric crowding of hemin species and their neighboring lateral interactions in the plane of hemin localization, affecting the potential distribution at the SAM/electrode interface and inducing local electrostatic effects interfering with hemin oxidation. In AUT/MC6OH and AUT/MC2OH SAMs, hemin discharged at the plane of the closest approach to the gold surface, equal to the diluent length and permeable to electrolyte ions, which lessened those effects. All studied binary SAMs provided steric hindrance for protein reconstitution on the hemin cofactor conjugated to the extended AUT linker. Further use of SAM-modified electrodes with the covalently attached hemin as interfaces for heme proteins' reconstitution should consider SAMs with loosely dispersed redox centers terminating more rigid molecular wires. Such wires place hemin at fixed distances from the electrode surface and thus ensure the interfacial properties required for the effective on-surface reconstitution of proteins and enzymes.


Portable Electrochemical DNA Sensors Based on Gene Amplification Reactions to Screen and Identify Pathogen and SNPs.
In this paper, we introduce portable sensors based on genetic measurements that can be used in the field for the diagnosis of infectious diseases and disease risk based on SNPs (single nucleotide polymorphisms). In particular, the sensors are based on electrochemical measurements that can be performed with printed electrodes and small measuring devices. Indicator molecules that can bind to nucleic acid molecules in various ways are already known, and some of these molecules have electrochemical activity. First, we investigated the change in their electrochemical responses in a solution system. As a result, we searched for nucleic acid-binding molecules whose current value changes in the presence of DNA. In addition, when we measured the change in the current value, associated with the amplification of specific genes, such as PCR (polymerase chain reaction) and LAMP (loop-mediated isothermal amplification), we found that the current value decreased with the number of amplifications, indicating that specific genes can be monitored electrochemically. Based on this principle, we showed that pathogenic microorganisms and viruses, such as Salmonella, O157 E. coli, hepatitis B virus, periodontal disease bacteria, antibiotic-resistant bacteria and influenza virus, were able to be measured. The method was also applied to the diagnosis of SNPs, such as ApoE (apolipoprotein E), which is a risk factor for Alzheimer's disease. Rapid PCR was available with a microfluidic device, and a simple method was also presented with the isothermal amplification of LAMP.


Training Program for Care Professionals in Nursing Homes: Effectiveness and Feasibility.
The aim of the current study was to analyze the effectiveness and feasibility of a training program for care professionals at two nursing homes, investigating the impact on their beliefs, attitudes, and knowledge regarding aging. Twenty-three formal caregivers at a private nursing home and 10 formal caregivers at a philanthropic nursing home participated in the training program, which consisted of five weekly meetings, each lasting 1.5 hours. Characterization of the sample was performed and effectiveness and feasibility of the intervention were analyzed. The training program improved participants' knowledge about older adults; however, their attitudes and beliefs regarding old age were not affected. Results also indicated that the intervention program was feasible at both nursing homes. The positive results of the study underscore the importance of training and continuing education of professionals who work with older adults, especially staff at nursing homes. [Journal of Gerontological Nursing, 46(11), 37-47.].


The goal-relevance of affective stimuli is dynamically represented in affective experience.
Affect is a continuous and temporally dependent process that represents an individual's ongoing relationship with its environment. However, there is a lack of evidence on how factors defining the dynamic sensory environment modulate changes in momentary affective experience. Here, we show that goal-dependent relevance of stimuli is a key factor shaping momentary affect in a dynamic context. Participants (N = 83) viewed sequentially presented images and reported their momentary affective experience after every fourth stimulus. Relevance was manipulated through an attentional task that rendered each image either task-relevant or task-irrelevant. Computational models were fitted to trial-by-trial affective responses to capture the key dynamic parameters explaining momentary affective experience. The findings from statistical analyses and computational models showed that momentary affective experience was shaped by the temporal integration of the affective impact of recently encountered stimuli, and that task-relevant stimuli, independent of stimulus affect, prompted larger changes in experienced pleasantness compared with task-irrelevant stimuli. These findings clearly show that dynamics of affective experience reflect goal-relevance of stimuli in our surroundings.


Can fluorescence spectrometry be used as a surrogate for predicting the dissolved organic nitrogen and its bioavailable portion in wastewater effluents?
This study investigated the applicability of fluorescence excitation-emission matrices coupled with parallel factor analysis (EEM-PARAFAC) for predicting dissolved organic nitrogen (DON) and bioavailable DON (ABDON) in wastewater effluents. A four component PARAFAC model was developed using 40 EEMs of effluent samples from four full-scale wastewater treatment plants. The DON showed a poor correlation with the PARAFAC components (-0.117 < r < 0.308, p = 0.053-0.471), while ABDON correlated significantly with protein-like components C2 (r = 0.511, p < 0.05) and C3 (r = 0.576, p < 0.05, Pearson test). Further, a multivariate linear regression model having a good predictive capability for ABDON with mean absolute error of 12.0% was developed. Results demonstrate that the application of fluorescence spectroscopy for predicting effluent DON may have limitations, however, it could provide an alternative tool for predicting effluent ABDON.


Primary meningeal rhabdomyosarcoma associated with chronic subdural effusion: case report.
Primary sarcomas of the CNS are rare and are sometimes associated with chronic subdural effusion (SDE). Approximately 10 patients with such presentations have been reported. The authors report the case of a 5-year-old boy with multiple subdural masses and SDE. An SDE had been diagnosed when the patient was 2 months old, and he received a subduroperitoneal shunt when he was 5 months old. Since then, he had been clinically stable and well for 5 years. When he presented with acute headache, nausea, and vomiting, a newly developed tumor was found. Near-total resection of the tumor was performed, and the mass was diagnosed as an embryonal-type rhabdomyosarcoma. The child was given radiation therapy and 13 cycles of chemotherapy and is still free of disease 13 months after surgery.


Compromised browning plasticity of primary subcutaneous adipocytes derived from overweight Chinese adults.
People with obesity have a compromised browning capacity of adipose tissue when faced with sympathetic stimuli. This study aimed to determine whether norepinephrine treatment can enhance the induction of precursor cells from human white adipose tissue to differentiate into adipocytes that express key markers of beige adipocytes, and if there is a difference in this capacity between normal weight and overweight individuals. Stromal vascular cells derived from subcutaneous white adipose tissue of normal weight and overweight groups were induced to differentiation, with or without norepinephrine, into adipocytes. Oxygen consumption rate, lipolysis, the expression of uncoupling protein 1 and other thermogenic genes were compared between different adiposity and treatment groups. Peroxisome proliferator activated receptor γ- coactivator-1 alpha (PGC-1 α) and uncoupling protein 1 gene expression increased significantly in the normal weight group, but not in the overweight group, with norepinephrine treatment. The increments of lipolysis and oxygen consumption rate were also higher in adipocytes from the normal weight group with norepinephrine treatment, as compared with those of the overweight group. PR domain containing protein 16 (PRDM 16) gene expression was higher in the normal weight group compared with that in the overweight group, while there were no significant changes found with norepinephrine treatment in either the normal weight or overweight group. Adipogenic precursor cells derived from overweight individuals were less prone to differentiate into beige-like adipocytes when facing sympathetic stimuli than normal weight ones, resulting in the compromised sympathetic-induced browning capacity in subcutaneous white adipose tissue in overweight individuals, which occurred before the onset of overt obesity.


Purification and characterization of recombinant Plasmodium falciparum adenylosuccinate synthetase expressed in Escherichia coli.
Most parasitic protozoa lack the de novo purine biosynthetic pathway and rely exclusively on the salvage pathway for their purine nucleotide requirements. Enzymes of the salvage pathway are, therefore, candidate drug targets. We have cloned the Plasmodium falciparum adenylosuccinate synthetase gene. In the parasite, adenylosuccinate synthetase is involved in the synthesis of AMP from IMP formed during the salvage of the purine base, hypoxanthine. The gene was shown to code for a functionally active protein by functional complementation in a purA mutant strain of Escherichia coli, H1238. This paper reports the conditions for hyperexpression of the recombinant protein in E. coli BL21(DE3) and purification of the protein to homogeneity. The enzyme was found to require the presence of dithiothreitol during the entire course of the purification for activity. Glycerol and EDTA were found to stabilize enzyme activity during storage. The specific activity of the purified protein was 1143.6 +/- 36.8 mUnits/mg. The K(M)s for the three substrates, GTP, IMP, and aspartate, were found to be 4.8 microM, 22.8 microM, and 1.4 mM, respectively. The enzyme was a dimer on gel filtration in buffers of low ionic strength but equilibrated between a monomer and a dimer in buffers of increased ionic strength.


Duty of candour requires better protection for nurses.
The report of the Mid Staffordshire NHS Foundation Trust public inquiry has a statutory duty of candor at its heart and the requirement for openness and transparency running through most of its 290 recommendations. While many will consider such a legal duty essential if a repeat of the Mid Staffordshire scandal is to be avoided, the duty is unlikely to be effective unless nurses can discharge their obligations without fear of recrimination. This article argues that current protection for nurses who report poor practice is inadequate and must be improved if the openness and transparency recommended is to become a reality in the NHS.


Nonequilibrium relaxation and aging scaling of the Coulomb and Bose glass.
We employ Monte Carlo simulations to investigate the nonequilibrium relaxation properties of the two- and three-dimensional Coulomb glass with different long-range repulsive interactions. Specifically, we explore the aging scaling laws in the two-time density autocorrelation function. We find that, in the time window and parameter range accessible to us, the scaling exponents are not universal, depending on the filling fraction and temperature: As either the temperature decreases or the filling fraction deviates more from half filling, the exponents reflect markedly slower relaxation kinetics. In comparison with a repulsive Coulomb potential, appropriate for impurity states in strongly disordered semiconductors, we observe that, for logarithmic interactions, the soft pseudogap in the density of states is considerably broader, and the dependence of the scaling exponents on external parameters is much weaker. The latter situation is relevant for flux creep in the disorder-dominated Bose glass phase of type-II superconductors subject to columnar pinning centers.


Adherence to antiretroviral therapy: a survey of factors associated with medication usage.
The use of highly active antiretroviral therapy (HAART) has decreased morbidity and mortality for people living with HIV/AIDS, but adherence to HAART is a critical factor in successful treatment. Adherence to medication is a complex and poorly understood behavior. A survey was undertaken to evaluate subjective correlates of adherence and non-adherence based on previously distilled themes from a qualitative study of adherence. A 60-question survey was completed by patients in the outpatient clinic setting regarding demographics, CD4 cell count, viral load, adherence, and screening questions about medication usage and attitudes toward HIV. Ninety-eight adherent and 34 non-adherent patients completed the survey. After logistic regression analysis, several questions appeared to be the main predictors of non-adherence: Have you ever thought of having HIV as a "punishment?" Do you feel that your medicines are hard to take? Do you believe the medicines for HIV that you take are working for you? These questions may be helpful in the development of a clinically useful screening tool to assess patients at risk for non-adherence.


Molecular Engineering of Polymyxin B for Imaging and Treatment of Bacterial Infections.
The emergence of multi-drug resistant bacteria and the lack of novel antibiotics to combat them have led to the revival of polymyxin B, a previously abandoned antibiotic due to its potential nephrotoxicity and neurotoxicity. To facilitate its widely clinical applications, increasing effort has been devoted to molecularly engineer polymyxin B for the targeted imaging and effective treatment of bacterial infections. Herein, the molecular engineering strategies will be summarized in this mini review, with selected recent advances for illustration. Perspective of the challenges and trends in this exciting and eagerly anticipated research area will also be provided in the end. We hope this mini review will inspire researchers from diverse fields to bring forward the next wave of exploiting molecular engineering approaches to propel the "old" polymyxin B to "new" clinical significance in combating bacterial infections.


Fraternine, a Novel Wasp Peptide, Protects against Motor Impairments in 6-OHDA Model of Parkinsonism.
Parkinson's disease (PD) is a progressive neurodegenerative condition that affects the Central Nervous System (CNS). Insect venoms show high molecular variability and selectivity in the CNS of mammals and present potential for the development of new drugs for the treatment of PD. In this study, we isolated and identified a component of the venom of the social wasp Parachartergus fraternus and evaluated its neuroprotective activity in the murine model of PD. For this purpose, the venom was filtered and separated through HPLC; fractions were analyzed through mass spectrometry and the active fraction was identified as a novel peptide, called Fraternine. We performed two behavioral tests to evaluate motor discoordination, as well as an apomorphine-induced rotation test. We also conducted an immunohistochemical assay to assess protection in TH+ neurons in the Substantia Nigra (SN) region. Group treated with 10 μg/animal of Fraternine remained longer in the rotarod compared to the lesioned group. In the apomorphine test, Fraternine decreased the number of rotations between treatments. This dose also inhibited dopaminergic neuronal loss, as indicated by immunohistochemical analysis. This study identified a novel peptide able to prevent the death of dopaminergic neurons of the SN and recover motor deficit in a 6-OHDA-induced murine model of PD.


Analysis of Ultrahigh Apparent Mobility in Oxide Field-Effect Transistors.
For newly developed semiconductors, obtaining high-performance transistors and identifying carrier mobility have been hot and important issues. Here, large-area fabrications and thorough analysis of InGaZnO transistors with enhanced current by simple encapsulations are reported. The enhancement in the drain current and on-off ratio is remarkable in the long-channel devices (e.g., 40 times in 200 µm long transistors) but becomes much less pronounced in short-channel devices (e.g., 2 times in 5 µm long transistors), which limits its application to the display industry. Combining gated four-probe measurements, scanning Kelvin-probe microscopy, secondary ion mass spectrometry, X-ray photoelectron spectroscopy, and device simulations, it is revealed that the enhanced apparent mobility up to several tens of times is attributed to the stabilized hydrogens in the middle area forming a degenerated channel area while that near the source-drain contacts are merely doped, which causes artifact in mobility extraction. The studies demonstrate the use of hydrogens to remarkably enhance performance of oxide transistors by inducing a new mode of device operation. Also, this study shows clearly that a thorough analysis is necessary to understand the origin of very high apparent mobilities in thin-film transistors or field-effect transistors with advanced semiconductors.


If animals know their own fighting ability, the evolutionarily stable level of fighting is reduced.
We consider a version of the Hawk-Dove game in which an animal knows its own fighting ability but not the ability of its opponent. For this game at evolutionary stability there is a critical level of ability such that animals with ability greater than the critical level play Hawk and animals with ability below the critical level play Dove. We define the level of fighting to be the probability of a Hawk-Hawk fight when two opponents meet. We show that even if an animal does not know the ability of its opponent, knowing its own ability results in a lower level of fighting at evolutionary stability than is found in the standard Hawk-Dove game in which there are no differences in ability or abilities are not known.


Initial experience with dual antiplatelet thromboprophylaxis using clopidogrel and aspirin in patients with mechanical aortic prostheses.
The aortic mechanical prosthesis (AMP) generates shear stress and causes erythrocyte fragmentation with ADP release that leads to platelet activation, the cause of thromboembolism. Thromboprophylaxis with the antiplatelet agents clopidogrel and aspirin (Clop-ASA) should reduce thromboembolic events in patients receiving an AMP. Over an eight-year period at the authors' institutions, a total of 135 patients underwent aortic valve replacement (AVR), with or without concomitant thoracic aortic procedures, and received Clop-ASA as thromboprophylaxis. Platelet reactivity was measured using the Verify Now system. Thromboelastography was commenced in August 2006, and patients were followed at six-month intervals, with echocardiography and assessment of platelet reactivity. The total follow up was 4,776 months (equivalent to 398 patient-years (pt-yr)); the average follow up was 35.4 +/- 25 months. During follow up, 18 patients (13.3%) died, eight from coronary artery disease and three from valve-related causes. Five patients (3.7%; 1.2%/pt-yr) had bleeding complications, but none experienced valve thrombosis. Two patients (1.5%; 0.5%/pt-yr) had a transient ischemic attack (TIA); one of these occurred in a patient who discontinued Clop-ASA, and the other in a responder to Clop-ASA. Seven patients (5.2%; 1.7%/pt-yr) had strokes, one of which occurred at 48.5 months after AVR. Of the remaining six patients who had a stroke, one was a non-responder to clopidogrel and five had stopped taking Clop-ASA. The incidence of strokes before using the Accumetrics and TEG devices was 2.5% per pt-yr, but only 1.0% per pt-yr thereafter. Thromboprophylaxis in patients with AMP receiving Clop-ASA seems to be effective. Patients had a low incidence of bleeding, TIA and ischemic stroke, and no valve thrombosis. The use of assays to determine platelet reactivity helped to identify those patients who were resistant to clopidogrel, hyporesponders, and poorly compliant patients. Notably, the incidence of strokes after implementing assays to monitor platelet reactivity was reduced. Deaths were due primarily to myocardial infarction, and none of the deaths was anticoagulant-related. Patients receiving Clop-ASA should undergo routine testing of platelet reactivity, and also continue antiplatelet therapy so as to reduce the risk of ischemic stroke.


Waveguide for air-coupled ultrasonic phased-arrays with propagation time compensation and plug-in assembly.
Waveguides allow grating lobe free beamforming for air-coupled ultrasonic phased-arrays by reducing the effective inter-element spacing to half wavelength. Since the sound waves propagate through the waveguide ducts, additional time delays are introduced. In this work, we present analytical, numerical, and experimental methods to estimate these time delays. Afterwards, two different waveguides are compared. The first one consists of equal-length ducts, requiring a time-consuming assembly process of the ultrasonic phased-array. In contrast, the second waveguide consists of Bézier-shaped ducts of unequal lengths but a planar input port allowing fast assembly. The analytical model is based on the geometric lengths of the waveguide ducts. The numerical model relies on a transient finite element analysis. All simulations are validated in an anechoic chamber using a calibrated microphone. The analytical (7.6% deviation) and numerical (3.2% deviation) propagation time models are in good agreement with the measurements. By using the analyzed propagation times for the compensation of the unequal waveguide duct lengths, we restored the beamforming capability without significant sound pressure level (SPL) loss. This work shows the possibility of reduced transducer assembly time for waveguided air-coupled phased-arrays without a reduced SPL.


Respiratory syncytial virus: co-infection and paediatric lower respiratory tract infections.
Comprehensive population-based data on the role of respiratory viruses in the development of lower respiratory tract infections (LRTIs) remain unclear. We investigated the incidence and effect of single and multiple infections with respiratory viruses on the risk of LRTIs in Vietnam. Population-based prospective surveillance and a case-control study of hospitalised paediatric patients with acute respiratory infection (ARI) were conducted from April 2007 through to March 2010. Healthy controls were randomly recruited from the same community. Nasopharyngeal samples were collected and tested for 13 respiratory viruses using multiplex PCRs. 1992 hospitalised ARI episodes, including 397 (19.9%) with LRTIs, were enrolled. Incidence of hospitalised LRTIs among children aged <24 months was 2171.9 per 100 000 (95% CI 1947.9-2419.7). The majority of ARI cases (60.9%) were positive for at least one virus. Human rhinovirus (24.2%), respiratory syncytial virus (20.1%) and influenza A virus (12.0%) were the most common and 9.5% had multiple-viral infections. Respiratory syncytial virus and human metapneumovirus infections independently increased the risk of LRTIs. Respiratory syncytial virus further increased the risk, when co-infected with human rhinovirus, human metapneumovirus and parainfluenza virus-3 but not with influenza A virus. The case-control analysis revealed that respiratory syncytial virus and influenza A virus increased the risk of ARI hospitalisation but not human rhinovirus. Respiratory syncytial virus is the leading pathogen associated with risk of ARI hospitalisation and LRTIs in Vietnam.


Draft Genome Sequence of Gluconobacter frateurii NBRC 103465, a Glyceric Acid-Producing Strain.
Gluconobacter frateurii strain NBRC 103465 can efficiently produce glyceric acid (GA) from raw glycerol feedstock derived from biodiesel fuel production processes. Here, we report the 3.4-Mb draft genome sequence of G. frateurii NBRC 103465. The draft genome sequence can be applied to examine the enzymes and electron transport system involved in GA production.


Spinal cord compression, infection, and unknown primary cancers.
The management of a patient with spinal cord compression can be complicated and challenging; however, this challenge becomes even more pronounced if the patient presents without a known cancer diagnosis in the context of progressive neurologic symptoms. Unless potential causes such as infection/tuberculosis are included in the differential diagnosis of an apparent unknown primary, then the correct diagnosis may be incorrectly determined.


Myocardial Injury After Noncardiac Surgery: A Systematic Review and Meta-Analysis.
Myocardial injury after noncardiac surgery (MINS) is a common postoperative complication associated with adverse cardiovascular outcomes. The purpose of this systematic review was to determine the incidence, clinical features, pathogenesis, management, and outcomes of MINS. We searched PubMed, Embase, Central and Web of Science databases for studies reporting the incidence, clinical features, and prognosis of MINS. Data analysis was performed with a mixed-methods approach, with quantitative analysis of meta-analytic methods for incidence, management, and outcomes, and a qualitative synthesis of the literature to determine associated preoperative factors and MINS pathogenesis. A total of 195 studies met study inclusion criteria. Among 169 studies reporting outcomes of 530,867 surgeries, the pooled incidence of MINS was 17.9% [95% confidence interval (CI), 16.2-19.6%]. Patients with MINS were older, more frequently men, and more likely to have cardiovascular risk factors and known coronary artery disease. Postoperative mortality was higher among patients with MINS than those without MINS, both in-hospital (8.1%, 95% CI, 4.4-12.7% vs 0.4%, 95% CI, 0.2-0.7%; relative risk 8.3, 95% CI, 4.2-16.6, P < 0.001) and at 1-year after surgery (20.6%, 95% CI, 15.9-25.7% vs 5.1%, 95% CI, 3.2-7.4%; relative risk 4.1, 95% CI, 3.0-5.6, P < 0.001). Few studies reported mechanisms of MINS or the medical treatment provided. In conclusion, MINS occurs frequently in clinical practice, is most common in patients with cardiovascular disease and its risk factors, and is associated with increased short- and long-term mortality. Additional investigation is needed to define strategies to prevent MINS and treat patients with this diagnosis.


Pulmonary Mucormycosis in an Immunocompetent Patient: A Rare Life-threatening Case.
Pulmonary mucormycosis is a rare but life-threatening, fungal infection that usually occurs in patients with immunocompromised conditions, such as diabetes mellitus and hematologic malignancies. Anti-fungals and/or surgery are treatment modalities for this disease. Isolated pulmonary mucormycosis in immunocompetent patient is extremely rare and a mortal fungal infection. Late diagnosis may cause increased morbidity and mortality. We report herein a case of an immunocompetent 37-year female, who presented with a massive hemoptysis and was treated with urgent right lower lobectomy on a suspicion of fungus ball on tomography scan. The specimen was reported as pulmonary mucormycosis on histopathological examination. Key Words: Mucormycosis, Hemoptysis, Cavitary lesion, Immunocompetent.


Function of Golgi-centrosome proximity in RPE-1 cells.
The close physical proximity between the Golgi and the centrosome is a unique feature of mammalian cells that has baffled scientists for years. Several knockdown and overexpression studies have linked the spatial relationship between these two organelles to the control of directional protein transport, directional migration, ciliogenesis and mitotic entry. However, most of these conditions have not only separated these two organelles, but also caused extensive fragmentation of the Golgi, making it difficult to dissect the specific contribution of Golgi-centrosome proximity. In this study, we present our results with stable retinal pigment epithelial (RPE-1) cell lines in which GM130 was knocked out using a CRISPR/Cas9 approach. While Golgi and centrosome organization appeared mostly intact in cells lacking GM130, there was a clear separation of these organelles from each other. We show that GM130 may control Golgi-centrosome proximity by anchoring AKAP450 to the Golgi. We also provide evidence that the physical proximity between these two organelles is dispensable for protein transport, cell migration, and ciliogenesis. These results suggest that Golgi-centrosome proximity per se is not necessary for the normal function of RPE-1 cells.


Validation of the clinical diagnostic criteria for temporomandibular disorders for the diagnostic subgroup - disc derangement with reduction.
Research is needed to assess the validity of the clinical diagnostic criteria for temporomandibular disorders (CDC/TMD). The purpose of this study was to test the reliability of the clinical diagnosis of temporomandibular joint (TMJ) internal derangement type (ID)-I as compared with the magnetic resonance imaging (MRI) 'gold standard'. The study comprised 168 TMJs in 84 patients, who were assigned a clinical TMJ-related diagnosis of ID-I (disc displacement with reduction) in at least one TMJ. Bilateral sagittal and coronal MR images were obtained subsequently to establish the corresponding diagnosis of the disc-condyle relationship. For the CDC/TMD interpretations, the positive predictive value (PPV) of ID-I for disc displacement with reduction (DDR) was 44%, and for the presence of an ID 69%. The overall diagnostic agreement for ID-I was 47.6% with a corresponding K-value of 0.05. Most of the disagreement was the result of the false-positive interpretations of ID-I, and false-negative interpretations of an 'absence of ID'. The results suggest CDC/TMD for ID-I to be insufficient reliable for determination of ID and/or DDR. Patients assigned a clinical TMJ-related diagnosis of ID-I may need to be supplemented by evidence from MRI to determine the functional 'disc-condyle relationship'.


[Study of hypertension in the Ivory Coast urban milieu].
The authors carried out a sample survey in the town of Abidjan to rate high blood-pressure in adult. They evaluate the prevalence rate of high blood-pressure at 13.4%. In this study one may consider as a risk factor: age, obesity, illiteracy, either in isolation and as a matter of course the three together. The role of age as confounding factor appears essential in pluri-factorial analysis and has to be systematically taken into account at the occasion of further studies.